BACKGROUND In recent years,the global prevalence of gastric cancer(GC)has witnessed a progressive decrease,accompanied by a step-growth in the incidence of gastric signet ring cell carcinoma(GSRCC).As precision medici...BACKGROUND In recent years,the global prevalence of gastric cancer(GC)has witnessed a progressive decrease,accompanied by a step-growth in the incidence of gastric signet ring cell carcinoma(GSRCC).As precision medicine concepts progress,GSRCC,a distinct sub-type of GC,has drawn considerable attention from researchers.However,there still persist some controversies regarding the associated research findings.AIM To summarize the current obstacles and potential future directions for research on GSRCC.METHODS To begin with,all literature related to GSRCC published from January 1,2004 to December 31,2023 was subjected to bibliometric analysis in this article.Additionally,this paper analyzed the research data using CiteSpace,GraphPad Prism v8.0.2,and VOSviewer,which was obtained from the Web of Science Core Collection database.The analysis results were visually represented.RESULTS This study provided a comprehensive overview of the statistical characteristics of the 995 English articles related to GSRCC,including cited references,authors,journals,countries,institutions,and keywords.The popular keywords and clusters contain"prognosis","survival","expression","histology",and"chemotherapy".CONCLUSION The prognosis,precise definition and classification,as well as chemoresistance of GSRCC,continue to be crucial areas of ongoing research,whose directions are closely tied to advancements in molecular biology research on GSRCC.展开更多
In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in ped...In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.展开更多
BACKGROUND At present,liver transplantation(LT)is one of the best treatments for hepatocellular carcinoma(HCC).Accurately predicting the survival status after LT can significantly improve the survival rate after LT,an...BACKGROUND At present,liver transplantation(LT)is one of the best treatments for hepatocellular carcinoma(HCC).Accurately predicting the survival status after LT can significantly improve the survival rate after LT,and ensure the best way to make rational use of liver organs.AIM To develop a model for predicting prognosis after LT in patients with HCC.METHODS Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated.The expression levels of alphafetoprotein(AFP),des-gamma-carboxy prothrombin,Golgi protein 73,cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer.The best cutoff value of biomarkers was determined using the Youden index.Cox regression analysis was used to identify the independent risk factors.A forest model was constructed using the random forest method.We evaluated the accuracy of the nomogram using the area under the curve,using the calibration curve to assess consistency.A decision curve analysis(DCA)was used to evaluate the clinical utility of the nomograms.RESULTS The total tumor diameter(TTD),vascular invasion(VI),AFP,and cytokeratin-18 epitopes M30(CK18-M30)were identified as important risk factors for outcome after LT.The nomogram had a higher predictive accuracy than the Milan,University of California,San Francisco,and Hangzhou criteria.The calibration curve analyses indicated a good fit.The survival and recurrence-free survival(RFS)of high-risk groups were significantly lower than those of low-and middle-risk groups(P<0.001).The DCA shows that the model has better clinical practicability.CONCLUSION The study developed a predictive nomogram based on TTD,VI,AFP,and CK18-M30 that could accurately predict overall survival and RFS after LT.It can screen for patients with better postoperative prognosis,and improve longterm survival for LT patients.展开更多
Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to expl...Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@SNP-OGP.The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular components(P<0.01).In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs,but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype(P<0.05 or P<0.01).The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways(P<0.01).In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model(P<0.01).Conclusions:Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.展开更多
Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attrac...Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.展开更多
Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of H...Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.展开更多
BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence...BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on H.pylori infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis,while patients with H.pylori infection were at lower risk.IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H.pylori infection;however,metabolic syndrome increased the risk of patients with H.pylori infection developing reflux esophagitis.展开更多
Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regen...Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.展开更多
BACKGROUND Liver metastases(LM)is the primary factor contributing to unfavorable outcomes in patients diagnosed with gastric cancer(GC).The objective of this study is to analyze significant prognostic risk factors for...BACKGROUND Liver metastases(LM)is the primary factor contributing to unfavorable outcomes in patients diagnosed with gastric cancer(GC).The objective of this study is to analyze significant prognostic risk factors for patients with GCLM and develop a reliable nomogram model that can accurately predict individualized prognosis,thereby enhancing the ability to evaluate patient outcomes.AIM To analyze prognostic risk factors for GCLM and develop a reliable nomogram model to accurately predict individualized prognosis,thereby enhancing patient outcome assessment.METHODS Retrospective analysis was conducted on clinical data pertaining to GCLM(type III),admitted to the Department of General Surgery across multiple centers of the Chinese PLA General Hospital from January 2010 to January 2018.The dataset was divided into a development cohort and validation cohort in a ratio of 2:1.In the development cohort,we utilized univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival in GCLM patients.Subsequently,we established a prediction model based on these findings and evaluated its performance using receiver operator characteristic curve analysis,calibration curves,and clinical decision curves.A nomogram was created to visually represent the prediction model,which was then externally validated using the validation cohort.RESULTS A total of 372 patients were included in this study,comprising 248 individuals in the development cohort and 124 individuals in the validation cohort.Based on Cox analysis results,our final prediction model incorporated five independent risk factors including albumin levels,primary tumor size,presence of extrahepatic metastases,surgical treatment status,and chemotherapy administration.The 1-,3-,and 5-years Area Under the Curve values in the development cohort are 0.753,0.859,and 0.909,respectively;whereas in the validation cohort,they are observed to be 0.772,0.848,and 0.923.Furthermore,the calibration curves demonstrated excellent consistency between observed values and actual values.Finally,the decision curve analysis curve indicated substantial net clinical benefit.CONCLUSION Our study identified significant prognostic risk factors for GCLM and developed a reliable nomogram model,demonstrating promising predictive accuracy and potential clinical benefit in evaluating patient outcomes.展开更多
AIM:To evaluate the diagnosis of different differentiated gastric intraepithelial neoplasia (IN) by magnifica-tion endoscopy combined with narrow-band imaging (ME-NBI) and confocal laser endomicroscopy (CLE). METHODS:...AIM:To evaluate the diagnosis of different differentiated gastric intraepithelial neoplasia (IN) by magnifica-tion endoscopy combined with narrow-band imaging (ME-NBI) and confocal laser endomicroscopy (CLE). METHODS:Eligible patients with suspected gastric IN lesions previously diagnosed by endoscopy in secondary hospitals and scheduled for further diagnosis and tratment were recruited for this study. Excluded from the study were patients who had liver cirrhosis, impaired renal function, acute gastrointestinal (GI) bleeding, coagulopathy, esophageal varices, jaundice, and GI post-surgery. Also excluded were those who were pregnant, breastfeeding, were younger than 18 years old, or were unable to provide informed consent. All patients had all mucus and bile cleared from their stom-achs. They then received upper GI endoscopy. When a mucosal lesion is found during observation with whitelight imaging, the lesion is visualized using maximal magnification, employing gradual movement of the tip of the endoscope to bring the image into focus. Saved images are analyzed. Confocal images were evaluated by two endoscopists (Huang J and Li MY), who were familiar with CLE, blinded to the related information about the lesions, and asked to classify each lesion as either a low grade dysplasia (LGD) or high grade dysplasia (HGD) according to given criteria. The results were compared with the final histopathologic diagnosis. ME-NBI images were evaluated by two endoscopists (Lu ZS and Ling-Hu EQ) who were familiar with NBI, blinded to the related information about the lesions and CLE images, and were asked to classify each lesion as a LGD or HGD according to the "microvascular pattern and surface pattern" classification system. The results were compared with the final histopathologic diagnosis. RESULTS: The study included 32 pathology-proven low grade gastric IN and 26 pathology-proven high grade gastric IN that were detected with any of the modalities. CLE and ME-NBI enabled clear visualization of the vascular microsurface patterns and microvascular structures of the gastric mucosa. The accuracy of the CLE and the ME-NBI diagnosis was 88% (95% CI:78%-98%) and 81% (95% CI: 69%-93%), respectively. The kappa coefficient of agreement between the histopathology and the in vivo CLE imaging was 0.755; between the histopathology and the in vivo CLE imaging was 0.615. McNemar's test (binomial distribution used) indicated that the agreement was significant (P < 0.05). When patients were diagnosed by MENBI with CLE, the overall accuracy of the diagnosis was 86.21% (95% CI:73%-96%), and the kappa coefficient of agreement was 0.713, according to McNemar's test (P < 0.05). CONCLUSION:Higher diagnostic accuracy, sensitivityand specificity of CLE over ME-NBI indicate the feasibility of these two techniques for the efficacious diagnostic classification of gastric IN.展开更多
The aim of management of hepatocellular carcinoma(HCC)is to improve the prognosis of the patients by radical resection and preserve remnant liver function.Although liver transplantation is associated with a lower tumo...The aim of management of hepatocellular carcinoma(HCC)is to improve the prognosis of the patients by radical resection and preserve remnant liver function.Although liver transplantation is associated with a lower tumor recurrence rate,this benefit is counteracted by long-term complications.Therefore,hepatectomy could be the first choice of treatment in selected patients with HCC.However,the higher frequency of tumor recurrence and the lower rate of resectability after hepatectomy for HCC led to an unsatisfactory prognosis.New strategies are required to improve the long-term outcome of HCC after hepatectomy.In this paper,we introduce some strategies to increase the low rate of resectability and reduce the high rate of tumor recurrence.Some aggressive treatments for tumor recurrence to extend long-term survival are also involved.We believe that hepatectomy combined with other therapies,such as portal vein embolization,transarterial chemoembolization,radioembolization,antiviral treatment,radiofrequency ablation and salvage transplantation,is a promising treatment modality for HCC and may improve survival greatly.展开更多
β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unkno...β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.展开更多
Objective: To explore the risk factors of intra-abdominal bacterial infection (IAI) after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Methods: A series of 82 HCC patients who re...Objective: To explore the risk factors of intra-abdominal bacterial infection (IAI) after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Methods: A series of 82 HCC patients who received LT surgeries in our department between March 2004 and April 2010 was recruited in this study. Then we collected and analyzed the clinical data retrospectively. Statistical analysis system (SPSS) software was adopted to perform statistical analysis. Chi-square test, t-test and Wilcoxon rank sum test were used to analyze the clinical data and compute the significance of the incidences of early-stage IAI after LT for HCC patients. Binary logistic regression was performed to screen out the risk factors, and multiple logistic regression analyses were performed to compute the independent risk factors. Results: A series of 13 patients (13/82, 15.9%) had postoperative IAI. The independent risk factors of postoperative intra-abdominal bacterial infections after LT for HCC patients were preoperative anemia [Hemoglobin (HGB) 〈90 g/L] and postoperative abdominal hemorrhage (72 hours 〉400 mL), with the odds ratios at 8.121 (95% CI, 1.417 to 46.550, P=0.019) and 5.911 (95% CI, 1.112 to 31.432, P=0.037). Conclusions: Postoperative IAI after LT in patients with HCC was a common complication. Preoperative moderate to severe anemia, as well as postoperative intra-abdominal hemorrhage more than 400 mL within the first 72 hours might independently indicate high risk of IAI for these patients.展开更多
AIM: To explore the changes of X-box binding protein 1splicing(XBP1s) and inflammatory cytokine expression in patients with ulcerative colitis(UC) in response to endoplasmic reticulum stress(ERS).METHODS: Reverse tran...AIM: To explore the changes of X-box binding protein 1splicing(XBP1s) and inflammatory cytokine expression in patients with ulcerative colitis(UC) in response to endoplasmic reticulum stress(ERS).METHODS: Reverse transcription polymerase chain reaction and quantitative polymerase chain reaction were performed to detect the forms of XBP1 s and the expression of interleukin(IL)-2, interferon(IFN)-γ, and IL-17α. Differences between patients with UC and normal subjects were then determined.RESULTS: Mononuclear cells of the peripheral blood of normal subjects and UC patients with were stimulated with no drugs(control), phytohemagglutinin(PHA), thapsigargin(TG), or both PHA and TG. XBP1 s in patients with UC exhibited splicing, which was greater with co-stimulation than single stimulation. Costimulation increased the expression level of IL-2, IFN-γ, and IL-17α.CONCLUSION: The T lymphocytes of both normal subjects and patients with UC responded to ERS by activating the XBP1s-mediated signalling pathway, upregulating the expression of inflammatory cytokines, and increasing the occurrence of inflammation. The mononuclear cells in the peripheral blood of patients with UC were more sensitive to ERS than those in the peripheral blood of normal subjects.展开更多
·AIM: To study the role of immature dendritic cells (imDCs) on immune tolerance in rat penetrating keratoplasty (PKP) in high -risk eyes and to investigate the mechanism of immune hyporesponsiveness induced by do...·AIM: To study the role of immature dendritic cells (imDCs) on immune tolerance in rat penetrating keratoplasty (PKP) in high -risk eyes and to investigate the mechanism of immune hyporesponsiveness induced by donor-derived imDCs. ·METHODS: Seventy-five SD rats (recipient) and 39 Wistar rats (donor) were randomly divided into 3 groups: control, imDC and mature dendritic cell (mDC) group respectively. Using a model of orthotopic corneal transplantation in which allografts were placed in neovascularized high -risk eyes of recipient rat. Corneal neovascularization was induced by alkaline burn in the central cornea of recipient rat. Recipients in imDC group or mDC group were injected donor bone marrow-derived imDCs or mDCs of 1 ×10 6 respectively 1 week before corneal transplantation tail vein. Control rat received the same volume of PBS. In each group, 16 recipients were kept for determination of survival time and other 9 recipients were executed on day 3, 7 and 14 after transplantation. Cornea was harvested for hematoxylin eosin staining and acute rejection evaluation, Western blot was used to detect the expression level of Foxp3. ·RESULTS: The mean survival time of imDC group was significantly longer than that of control and mDC groups (all 【0.05). The expression level of Foxp3 on CD4 + CD25 + T cells of imDC group (2.24 ±0.18) was significantly higher than that in the control (1.68 ±0.09) and mDC groups (1.46±0.13) (all 【0.05).·CONCLUSION: Donor -derived imDC is an effective treatment in inducing immune hyporesponsiveness in rat PKP. The mechanism of immune tolerance induced by imDC might be inhibit T lymphocytes responsiveness by regulatory T cells. ·展开更多
BACKGROUND Focal nodal hyperplasia(FNH)is a common benign tumor of the liver.It occurs mostly in people aged 40-50 years and 90%of the patients are female.FNH can be cured by local resection.How to locate and judge th...BACKGROUND Focal nodal hyperplasia(FNH)is a common benign tumor of the liver.It occurs mostly in people aged 40-50 years and 90%of the patients are female.FNH can be cured by local resection.How to locate and judge the tumor boundary in real time is often a challenge for surgeons.AIM To summarize the technique and feasibility of robotic resection of FNH guided by indocyanine green(ICG)fluorescence imaging.METHODS The demographics and perioperative outcomes of a consecutive series of patients who underwent robotic resection of liver FNH guided by ICG fluorescence imaging between May 1,2018 and September 30,2019 were retrospectively analyzed.ICG was injected through the median elbow vein in all the patients at a dose of 0.25 mg/kg 48 h before the operation.During the operation,the position of FNH in the liver was located in the fluorescence mode of the Da Vinci Si robot operating system and the tumor boundary was determined during the resection.RESULTS Among the 23 patients,there were 11 males and 12 females,with a mean age of 30.5±9.3 years.Twenty-two cases completed robotic resection,while one(4.3%)case converted to open surgery.In the robotic surgery group,the operation time was 35-340 min with a median of 120 min,the intraoperative bleeding was 10-800 m L with a median of 50 m L,and the postoperative hospital stay was 1-7 d with a median of 4 d.Biliary fistula occurred in two(8.7%)patients after robotic operation and they both recovered after conservative treatment.One(4.3%)patient received blood transfusion and there was no death in this study.The postoperative hospital stay in the small tumor group was significantly shorter than that in the large tumor group(P<0.05).CONCLUSION ICG fluorescence imaging can guide the surgeon to perform robotic resection of liver FNH by locating the tumor and displaying the tumor boundary in real time.It is a safe and feasible method to ensure the complete resection of the tumor.展开更多
The zonal disintegration phenomenon (ZDP) is a typical phenomenon in deep block rock masses. In order to investigate the mechanism of ZDP, an improved non-linear Hock-Brown strength criterion and a bi-linear constit...The zonal disintegration phenomenon (ZDP) is a typical phenomenon in deep block rock masses. In order to investigate the mechanism of ZDP, an improved non-linear Hock-Brown strength criterion and a bi-linear constitutive model of rock mass were used to analyze the elasto-plastic stress field of the enclosing rock mass around a deep round tunnel. The radius of the plastic region and stress of the enclosing rock mass were obtained by introducing dimensionless parameters of radial distance. The results show that tunneling in deep rock mass causes a maximum stress zone to appear in the vicinity of the boundary of the elastic and the plastic zone in the surrounding rock mass. Under the compression of a large tangential force and a small radial force, the rock mass in the maximum stress zone was in an approximate uniaxial loading state, which could lead to a split failure in the rock mass.展开更多
Aim: To assess the quality of high-resolution CT section planes(HRCT), multi-planar reformation(MPR) and 3-dimensional volume rendered computer tomography(3D-CTVR) were here used in the fine differential diagnosis of ...Aim: To assess the quality of high-resolution CT section planes(HRCT), multi-planar reformation(MPR) and 3-dimensional volume rendered computer tomography(3D-CTVR) were here used in the fine differential diagnosis of ossicular chain in the case of conductive hearing loss with intact tympanic membrane.Methods: Here, 17 cases of otosclerosis and 22 cases of ossicular chain deformity were selected. All patients had normal external ear canals,intact tympanic membranes, conductive hearing loss, type A tympanograms, and negative Gelle's tests. The respective radiological reports of the status of the ossicles via 3 protocols were compared to surgical findings. The quantitative assessments of the representation of different segments of the ossicular chain were based on a 3-point scoring system.Results: MPR and CTVR imaging both showed the integrity of whole ossicular chain well. MPR and CTVR imaging were found to be superior to section planes with respect to showing the superstructure of the stapes and malformations(P > 0.05).Conclusion: CTVR and MPR imaging were found to be better able to show the whole ossicular chain in the conductive hearing loss with normal tympanic membranes. Furthermore, the use of these techniques can have profound contributive value in the differential diagnosis of otosclerosis and ossicular chain absence or malformation.展开更多
BACKGROUND: Carotid artery is the main source for craniocerebral blood supply. Its intimal plaque formation and arterial stenosis degree both are the risk factors for ischemic cerebrovascular disease.Therefore, the c...BACKGROUND: Carotid artery is the main source for craniocerebral blood supply. Its intimal plaque formation and arterial stenosis degree both are the risk factors for ischemic cerebrovascular disease.Therefore, the close relationship of carotid atherosclerotic plaque and ischemic cerebrovascular disease, and ultrasound evaluation of carotid atherosclerotic plaque have become the hot spot in studying ischemic cerebrovascular disease.OBJECTIVE: This study was to detect the degree of carotid atherosclerosis of ischemic cerebrovascular disease patients by ultrasonography, and to analyze the situation of carotid atherosclerosis and its relationship with clinic.DESIGN: Clinical randomized concurrent control experiment.SETTING: Lintong Convalescent Hospital of Lanzhou Military Area Command of Chinese PLA.PARTICIPANTS: Totally 60 outpatients and inpatients with ischemic cerebrovascular disease, 42 males and 18 females, admitted to Lintong Convalescent Hospital of Lanzhou Military Area Command of Chinese PLA between January 2006 and December 2006 were involved in the patient group. They met the diagnosis criteria of ischemic cerebrovascular disease constituted by the 4th Cerebrovascular Disease Conference in 1996, and were confirmed to suffer from ischemic cerebrovascular disease by skull CT and MRI. Another 20 subjects who received healthy examination concurrently in the same hospital, 12 males and 8 females, were involved in the control group. Informed consents of detected items were obtained from involved subjects.METHODS: The plaque thickness of mid portion, distal end and crotch of common carotid artery (CCA),internal carotid artery (ICA), external carotid artery (ECA) and vertebral artery (VA) of involved subjects,who received health examination was separately detected with color Doppler ultrasonograph (HDI-5000).Then, total integral of plaque was calculated. The intima-media thickness (IMT) was measured with two-dimensional ultrasonography. The inner diameter stenosis degree of subjects who had plaque was measured. Blood flow parameters were recorded, and stenosis degree and plaque area were calculated. Blood flow volume of bilateral carotid artery and VA was separately measured with ultrasound equipment software,and brain blood flow volume was calculated.MAIN OUTCOME MEASURES: Atherosclerotic degree and blood flow volume of patients of two groups.RESULTS: Sixty patients with ischemic cerebrovascular disease and twenty subjects who received health examination participated in the final analysis. ①The IMT thickness, total plaque score, and total plaque area of patient group was significantly superior to that of control group, respectively( t=5.216 - 10.158, P 〈 0.05 ).② There were significant differences in the stenosis degree of CCA, ICA and VA between patient group and control group (t=6.720 - 12.816, P 〈 0.05 ) . ③ The blood flow volume of CCA, ICA, VA and brain of patient group was significantly lower than that of control group, respectively (t=2.872 - 10.860, P 〈 0.05).CONCLUSION: Ischemic cerebrovascular disease patients have different degrees of changes in atherosclerosis and arterial blood flow.展开更多
We present a female patient with preterm labor, severe viral hepatitis B of acute phase, hepatic encephalopathy stage Ⅲ and coma.After delivery, the illness was exacerbated and the patient presented with clinical sig...We present a female patient with preterm labor, severe viral hepatitis B of acute phase, hepatic encephalopathy stage Ⅲ and coma.After delivery, the illness was exacerbated and the patient presented with clinical signs of vital organ dysfunctions such as acute respiratory distress syndrome, cerebral edema and hypoxemia that needed mechanical ventilation.Emergency liver transplantation was recommended after multidisciplinary panel consultations.The donor, her mother, consented to donate her right liver.Auxiliary partial orthotopic living donor liver transplantion(APOLDLT) was performed.After operation, the patient was on triple medication of tacrolimus plus mofetil mycophenolate and prednisone for immunosuppression.The combination of antihepatitis B virus(HBV) immunoglobulin and entecavir was initiated for anti-HBV therapy.Both the patient and the donor recovered well without any complications.The patient was followed up regularly.Her liver function, clinical signs and symptoms improved significantly.Until now, the recipient has been living for more than 78 mo free of any complications.The APOLDLT is a life-saving modality for rescuing patients with high-risk acute liver failure following HBV infection without available donor and hence is recommended under standardized antiviral therapy coverage as stated above.展开更多
基金Supported by National Natural Science Foundation of China,No.82073192,and No.82273231Beijing Science and Technology Program,No.Z221100007422125.
文摘BACKGROUND In recent years,the global prevalence of gastric cancer(GC)has witnessed a progressive decrease,accompanied by a step-growth in the incidence of gastric signet ring cell carcinoma(GSRCC).As precision medicine concepts progress,GSRCC,a distinct sub-type of GC,has drawn considerable attention from researchers.However,there still persist some controversies regarding the associated research findings.AIM To summarize the current obstacles and potential future directions for research on GSRCC.METHODS To begin with,all literature related to GSRCC published from January 1,2004 to December 31,2023 was subjected to bibliometric analysis in this article.Additionally,this paper analyzed the research data using CiteSpace,GraphPad Prism v8.0.2,and VOSviewer,which was obtained from the Web of Science Core Collection database.The analysis results were visually represented.RESULTS This study provided a comprehensive overview of the statistical characteristics of the 995 English articles related to GSRCC,including cited references,authors,journals,countries,institutions,and keywords.The popular keywords and clusters contain"prognosis","survival","expression","histology",and"chemotherapy".CONCLUSION The prognosis,precise definition and classification,as well as chemoresistance of GSRCC,continue to be crucial areas of ongoing research,whose directions are closely tied to advancements in molecular biology research on GSRCC.
文摘In this article,we comment on an article published in a recent issue of the World Journal of Gastroenterology.We specifically focus on the roles of human leukocyte antigen(HLA)and donor-specific antibodies(DSAs)in pediatric liver transpl-antation(LT),as well as the relationship between immune rejection after LT and DSA.Currently,LT remains the standard of care for pediatric patients with end-stage liver disease or severe acute liver failure.However,acute and chronic re-jection continues to be a significant cause of graft dysfunction and loss.HLA mismatch significantly reduces graft survival and increases the risk of acute rejection.Among them,D→R one-way mismatch at three loci was significantly related to graft-versus-host disease incidence after LT.The adverse impact of HLA-DSAs on LT recipients is already established.Therefore,the evaluation of HLA and DSA is crucial in pediatric LT.
基金Supported by the National Natural Science Foundation of China,No.81372595 and No.81972696.
文摘BACKGROUND At present,liver transplantation(LT)is one of the best treatments for hepatocellular carcinoma(HCC).Accurately predicting the survival status after LT can significantly improve the survival rate after LT,and ensure the best way to make rational use of liver organs.AIM To develop a model for predicting prognosis after LT in patients with HCC.METHODS Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated.The expression levels of alphafetoprotein(AFP),des-gamma-carboxy prothrombin,Golgi protein 73,cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer.The best cutoff value of biomarkers was determined using the Youden index.Cox regression analysis was used to identify the independent risk factors.A forest model was constructed using the random forest method.We evaluated the accuracy of the nomogram using the area under the curve,using the calibration curve to assess consistency.A decision curve analysis(DCA)was used to evaluate the clinical utility of the nomograms.RESULTS The total tumor diameter(TTD),vascular invasion(VI),AFP,and cytokeratin-18 epitopes M30(CK18-M30)were identified as important risk factors for outcome after LT.The nomogram had a higher predictive accuracy than the Milan,University of California,San Francisco,and Hangzhou criteria.The calibration curve analyses indicated a good fit.The survival and recurrence-free survival(RFS)of high-risk groups were significantly lower than those of low-and middle-risk groups(P<0.001).The DCA shows that the model has better clinical practicability.CONCLUSION The study developed a predictive nomogram based on TTD,VI,AFP,and CK18-M30 that could accurately predict overall survival and RFS after LT.It can screen for patients with better postoperative prognosis,and improve longterm survival for LT patients.
基金financially supported by the National Natural Science Foundation of China(82101069,82102537,82160411,82002278)the Natural Science Foundation of Chongqing Science and Technology Commission(CSTC2021JCYJ-MSXMX0170,CSTB2022BSXM-JCX0039)+2 种基金the First Affiliated Hospital of Chongqing Medical University Cultivating Fund(PYJJ2021-02)the Beijing Municipal Science&Technology Commission(Z221100007422130)the Youth Incubation Program of Medical Science and Technology of PLA(21QNPY116).
文摘Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@SNP-OGP.The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular components(P<0.01).In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs,but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype(P<0.05 or P<0.01).The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways(P<0.01).In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model(P<0.01).Conclusions:Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.
基金the National Natural Science Foundation of China(Grant No.:51803120).
文摘Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology therapy.Cetuximab(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single use.Cisplatin(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major drawbacks.In this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and Cet.The so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in cSCC.Specifically,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and CisPt.Herein,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.
基金supported by the National Natural Science Foundation of China(No.82073617)Joint Research Fund for Beijing Natural Science Foundation and Haidian Original Innovation(No.L202007)+1 种基金Fundamental Research Funds for the Central Universities and Peking University Health Science Center(No.BMU2021YJ041)Peking University Medicine Fund of Fostering Young Scholars'Scientific&Technological Innovation(No.BMU2021PY005).
文摘Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.
基金This study was reviewed and approved by the Ethics Committee of the PLA General Hospital(Ethics audits No.S2022-414-01).
文摘BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on H.pylori infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis,while patients with H.pylori infection were at lower risk.IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H.pylori infection;however,metabolic syndrome increased the risk of patients with H.pylori infection developing reflux esophagitis.
基金supported by the National Natural Science Foundation of China,Nos.82271397(to MG),82001293(to MG),82171355(to RX),81971295(to RX)and 81671189(to RX)。
文摘Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.
文摘BACKGROUND Liver metastases(LM)is the primary factor contributing to unfavorable outcomes in patients diagnosed with gastric cancer(GC).The objective of this study is to analyze significant prognostic risk factors for patients with GCLM and develop a reliable nomogram model that can accurately predict individualized prognosis,thereby enhancing the ability to evaluate patient outcomes.AIM To analyze prognostic risk factors for GCLM and develop a reliable nomogram model to accurately predict individualized prognosis,thereby enhancing patient outcome assessment.METHODS Retrospective analysis was conducted on clinical data pertaining to GCLM(type III),admitted to the Department of General Surgery across multiple centers of the Chinese PLA General Hospital from January 2010 to January 2018.The dataset was divided into a development cohort and validation cohort in a ratio of 2:1.In the development cohort,we utilized univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival in GCLM patients.Subsequently,we established a prediction model based on these findings and evaluated its performance using receiver operator characteristic curve analysis,calibration curves,and clinical decision curves.A nomogram was created to visually represent the prediction model,which was then externally validated using the validation cohort.RESULTS A total of 372 patients were included in this study,comprising 248 individuals in the development cohort and 124 individuals in the validation cohort.Based on Cox analysis results,our final prediction model incorporated five independent risk factors including albumin levels,primary tumor size,presence of extrahepatic metastases,surgical treatment status,and chemotherapy administration.The 1-,3-,and 5-years Area Under the Curve values in the development cohort are 0.753,0.859,and 0.909,respectively;whereas in the validation cohort,they are observed to be 0.772,0.848,and 0.923.Furthermore,the calibration curves demonstrated excellent consistency between observed values and actual values.Finally,the decision curve analysis curve indicated substantial net clinical benefit.CONCLUSION Our study identified significant prognostic risk factors for GCLM and developed a reliable nomogram model,demonstrating promising predictive accuracy and potential clinical benefit in evaluating patient outcomes.
文摘AIM:To evaluate the diagnosis of different differentiated gastric intraepithelial neoplasia (IN) by magnifica-tion endoscopy combined with narrow-band imaging (ME-NBI) and confocal laser endomicroscopy (CLE). METHODS:Eligible patients with suspected gastric IN lesions previously diagnosed by endoscopy in secondary hospitals and scheduled for further diagnosis and tratment were recruited for this study. Excluded from the study were patients who had liver cirrhosis, impaired renal function, acute gastrointestinal (GI) bleeding, coagulopathy, esophageal varices, jaundice, and GI post-surgery. Also excluded were those who were pregnant, breastfeeding, were younger than 18 years old, or were unable to provide informed consent. All patients had all mucus and bile cleared from their stom-achs. They then received upper GI endoscopy. When a mucosal lesion is found during observation with whitelight imaging, the lesion is visualized using maximal magnification, employing gradual movement of the tip of the endoscope to bring the image into focus. Saved images are analyzed. Confocal images were evaluated by two endoscopists (Huang J and Li MY), who were familiar with CLE, blinded to the related information about the lesions, and asked to classify each lesion as either a low grade dysplasia (LGD) or high grade dysplasia (HGD) according to given criteria. The results were compared with the final histopathologic diagnosis. ME-NBI images were evaluated by two endoscopists (Lu ZS and Ling-Hu EQ) who were familiar with NBI, blinded to the related information about the lesions and CLE images, and were asked to classify each lesion as a LGD or HGD according to the "microvascular pattern and surface pattern" classification system. The results were compared with the final histopathologic diagnosis. RESULTS: The study included 32 pathology-proven low grade gastric IN and 26 pathology-proven high grade gastric IN that were detected with any of the modalities. CLE and ME-NBI enabled clear visualization of the vascular microsurface patterns and microvascular structures of the gastric mucosa. The accuracy of the CLE and the ME-NBI diagnosis was 88% (95% CI:78%-98%) and 81% (95% CI: 69%-93%), respectively. The kappa coefficient of agreement between the histopathology and the in vivo CLE imaging was 0.755; between the histopathology and the in vivo CLE imaging was 0.615. McNemar's test (binomial distribution used) indicated that the agreement was significant (P < 0.05). When patients were diagnosed by MENBI with CLE, the overall accuracy of the diagnosis was 86.21% (95% CI:73%-96%), and the kappa coefficient of agreement was 0.713, according to McNemar's test (P < 0.05). CONCLUSION:Higher diagnostic accuracy, sensitivityand specificity of CLE over ME-NBI indicate the feasibility of these two techniques for the efficacious diagnostic classification of gastric IN.
基金Supported by Grants from the National Natural Science Foundation of China,No.30772493 and No.81170429
文摘The aim of management of hepatocellular carcinoma(HCC)is to improve the prognosis of the patients by radical resection and preserve remnant liver function.Although liver transplantation is associated with a lower tumor recurrence rate,this benefit is counteracted by long-term complications.Therefore,hepatectomy could be the first choice of treatment in selected patients with HCC.However,the higher frequency of tumor recurrence and the lower rate of resectability after hepatectomy for HCC led to an unsatisfactory prognosis.New strategies are required to improve the long-term outcome of HCC after hepatectomy.In this paper,we introduce some strategies to increase the low rate of resectability and reduce the high rate of tumor recurrence.Some aggressive treatments for tumor recurrence to extend long-term survival are also involved.We believe that hepatectomy combined with other therapies,such as portal vein embolization,transarterial chemoembolization,radioembolization,antiviral treatment,radiofrequency ablation and salvage transplantation,is a promising treatment modality for HCC and may improve survival greatly.
基金supported by the National Natural Science Foundation of China,Nos.82104158(to XT),31800887(to LY),31972902(to LY),82001422(to YL)China Postdoctoral Science Foundation,No.2020M683750(to LY)partially by Young Talent Fund of University Association for Science and Technology in Shaanxi Province of China,No.20200307(to LY).
文摘β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.
基金funded by a new round of the ShanghaiHealth System outstanding young talent training plan (XYQ2011030)
文摘Objective: To explore the risk factors of intra-abdominal bacterial infection (IAI) after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Methods: A series of 82 HCC patients who received LT surgeries in our department between March 2004 and April 2010 was recruited in this study. Then we collected and analyzed the clinical data retrospectively. Statistical analysis system (SPSS) software was adopted to perform statistical analysis. Chi-square test, t-test and Wilcoxon rank sum test were used to analyze the clinical data and compute the significance of the incidences of early-stage IAI after LT for HCC patients. Binary logistic regression was performed to screen out the risk factors, and multiple logistic regression analyses were performed to compute the independent risk factors. Results: A series of 13 patients (13/82, 15.9%) had postoperative IAI. The independent risk factors of postoperative intra-abdominal bacterial infections after LT for HCC patients were preoperative anemia [Hemoglobin (HGB) 〈90 g/L] and postoperative abdominal hemorrhage (72 hours 〉400 mL), with the odds ratios at 8.121 (95% CI, 1.417 to 46.550, P=0.019) and 5.911 (95% CI, 1.112 to 31.432, P=0.037). Conclusions: Postoperative IAI after LT in patients with HCC was a common complication. Preoperative moderate to severe anemia, as well as postoperative intra-abdominal hemorrhage more than 400 mL within the first 72 hours might independently indicate high risk of IAI for these patients.
基金Beijing Municipal Natural Scientific Research Foundation,No.7132175
文摘AIM: To explore the changes of X-box binding protein 1splicing(XBP1s) and inflammatory cytokine expression in patients with ulcerative colitis(UC) in response to endoplasmic reticulum stress(ERS).METHODS: Reverse transcription polymerase chain reaction and quantitative polymerase chain reaction were performed to detect the forms of XBP1 s and the expression of interleukin(IL)-2, interferon(IFN)-γ, and IL-17α. Differences between patients with UC and normal subjects were then determined.RESULTS: Mononuclear cells of the peripheral blood of normal subjects and UC patients with were stimulated with no drugs(control), phytohemagglutinin(PHA), thapsigargin(TG), or both PHA and TG. XBP1 s in patients with UC exhibited splicing, which was greater with co-stimulation than single stimulation. Costimulation increased the expression level of IL-2, IFN-γ, and IL-17α.CONCLUSION: The T lymphocytes of both normal subjects and patients with UC responded to ERS by activating the XBP1s-mediated signalling pathway, upregulating the expression of inflammatory cytokines, and increasing the occurrence of inflammation. The mononuclear cells in the peripheral blood of patients with UC were more sensitive to ERS than those in the peripheral blood of normal subjects.
基金Military Medical Research Projects Fund of China (No. CLZ11JA25)
文摘·AIM: To study the role of immature dendritic cells (imDCs) on immune tolerance in rat penetrating keratoplasty (PKP) in high -risk eyes and to investigate the mechanism of immune hyporesponsiveness induced by donor-derived imDCs. ·METHODS: Seventy-five SD rats (recipient) and 39 Wistar rats (donor) were randomly divided into 3 groups: control, imDC and mature dendritic cell (mDC) group respectively. Using a model of orthotopic corneal transplantation in which allografts were placed in neovascularized high -risk eyes of recipient rat. Corneal neovascularization was induced by alkaline burn in the central cornea of recipient rat. Recipients in imDC group or mDC group were injected donor bone marrow-derived imDCs or mDCs of 1 ×10 6 respectively 1 week before corneal transplantation tail vein. Control rat received the same volume of PBS. In each group, 16 recipients were kept for determination of survival time and other 9 recipients were executed on day 3, 7 and 14 after transplantation. Cornea was harvested for hematoxylin eosin staining and acute rejection evaluation, Western blot was used to detect the expression level of Foxp3. ·RESULTS: The mean survival time of imDC group was significantly longer than that of control and mDC groups (all 【0.05). The expression level of Foxp3 on CD4 + CD25 + T cells of imDC group (2.24 ±0.18) was significantly higher than that in the control (1.68 ±0.09) and mDC groups (1.46±0.13) (all 【0.05).·CONCLUSION: Donor -derived imDC is an effective treatment in inducing immune hyporesponsiveness in rat PKP. The mechanism of immune tolerance induced by imDC might be inhibit T lymphocytes responsiveness by regulatory T cells. ·
文摘BACKGROUND Focal nodal hyperplasia(FNH)is a common benign tumor of the liver.It occurs mostly in people aged 40-50 years and 90%of the patients are female.FNH can be cured by local resection.How to locate and judge the tumor boundary in real time is often a challenge for surgeons.AIM To summarize the technique and feasibility of robotic resection of FNH guided by indocyanine green(ICG)fluorescence imaging.METHODS The demographics and perioperative outcomes of a consecutive series of patients who underwent robotic resection of liver FNH guided by ICG fluorescence imaging between May 1,2018 and September 30,2019 were retrospectively analyzed.ICG was injected through the median elbow vein in all the patients at a dose of 0.25 mg/kg 48 h before the operation.During the operation,the position of FNH in the liver was located in the fluorescence mode of the Da Vinci Si robot operating system and the tumor boundary was determined during the resection.RESULTS Among the 23 patients,there were 11 males and 12 females,with a mean age of 30.5±9.3 years.Twenty-two cases completed robotic resection,while one(4.3%)case converted to open surgery.In the robotic surgery group,the operation time was 35-340 min with a median of 120 min,the intraoperative bleeding was 10-800 m L with a median of 50 m L,and the postoperative hospital stay was 1-7 d with a median of 4 d.Biliary fistula occurred in two(8.7%)patients after robotic operation and they both recovered after conservative treatment.One(4.3%)patient received blood transfusion and there was no death in this study.The postoperative hospital stay in the small tumor group was significantly shorter than that in the large tumor group(P<0.05).CONCLUSION ICG fluorescence imaging can guide the surgeon to perform robotic resection of liver FNH by locating the tumor and displaying the tumor boundary in real time.It is a safe and feasible method to ensure the complete resection of the tumor.
基金Projects 50525825, 50490275 and 90815010 supported by the National Natural Science Foundation of China2009CB724608 by the National BasicResearch Program of China
文摘The zonal disintegration phenomenon (ZDP) is a typical phenomenon in deep block rock masses. In order to investigate the mechanism of ZDP, an improved non-linear Hock-Brown strength criterion and a bi-linear constitutive model of rock mass were used to analyze the elasto-plastic stress field of the enclosing rock mass around a deep round tunnel. The radius of the plastic region and stress of the enclosing rock mass were obtained by introducing dimensionless parameters of radial distance. The results show that tunneling in deep rock mass causes a maximum stress zone to appear in the vicinity of the boundary of the elastic and the plastic zone in the surrounding rock mass. Under the compression of a large tangential force and a small radial force, the rock mass in the maximum stress zone was in an approximate uniaxial loading state, which could lead to a split failure in the rock mass.
文摘Aim: To assess the quality of high-resolution CT section planes(HRCT), multi-planar reformation(MPR) and 3-dimensional volume rendered computer tomography(3D-CTVR) were here used in the fine differential diagnosis of ossicular chain in the case of conductive hearing loss with intact tympanic membrane.Methods: Here, 17 cases of otosclerosis and 22 cases of ossicular chain deformity were selected. All patients had normal external ear canals,intact tympanic membranes, conductive hearing loss, type A tympanograms, and negative Gelle's tests. The respective radiological reports of the status of the ossicles via 3 protocols were compared to surgical findings. The quantitative assessments of the representation of different segments of the ossicular chain were based on a 3-point scoring system.Results: MPR and CTVR imaging both showed the integrity of whole ossicular chain well. MPR and CTVR imaging were found to be superior to section planes with respect to showing the superstructure of the stapes and malformations(P > 0.05).Conclusion: CTVR and MPR imaging were found to be better able to show the whole ossicular chain in the conductive hearing loss with normal tympanic membranes. Furthermore, the use of these techniques can have profound contributive value in the differential diagnosis of otosclerosis and ossicular chain absence or malformation.
文摘BACKGROUND: Carotid artery is the main source for craniocerebral blood supply. Its intimal plaque formation and arterial stenosis degree both are the risk factors for ischemic cerebrovascular disease.Therefore, the close relationship of carotid atherosclerotic plaque and ischemic cerebrovascular disease, and ultrasound evaluation of carotid atherosclerotic plaque have become the hot spot in studying ischemic cerebrovascular disease.OBJECTIVE: This study was to detect the degree of carotid atherosclerosis of ischemic cerebrovascular disease patients by ultrasonography, and to analyze the situation of carotid atherosclerosis and its relationship with clinic.DESIGN: Clinical randomized concurrent control experiment.SETTING: Lintong Convalescent Hospital of Lanzhou Military Area Command of Chinese PLA.PARTICIPANTS: Totally 60 outpatients and inpatients with ischemic cerebrovascular disease, 42 males and 18 females, admitted to Lintong Convalescent Hospital of Lanzhou Military Area Command of Chinese PLA between January 2006 and December 2006 were involved in the patient group. They met the diagnosis criteria of ischemic cerebrovascular disease constituted by the 4th Cerebrovascular Disease Conference in 1996, and were confirmed to suffer from ischemic cerebrovascular disease by skull CT and MRI. Another 20 subjects who received healthy examination concurrently in the same hospital, 12 males and 8 females, were involved in the control group. Informed consents of detected items were obtained from involved subjects.METHODS: The plaque thickness of mid portion, distal end and crotch of common carotid artery (CCA),internal carotid artery (ICA), external carotid artery (ECA) and vertebral artery (VA) of involved subjects,who received health examination was separately detected with color Doppler ultrasonograph (HDI-5000).Then, total integral of plaque was calculated. The intima-media thickness (IMT) was measured with two-dimensional ultrasonography. The inner diameter stenosis degree of subjects who had plaque was measured. Blood flow parameters were recorded, and stenosis degree and plaque area were calculated. Blood flow volume of bilateral carotid artery and VA was separately measured with ultrasound equipment software,and brain blood flow volume was calculated.MAIN OUTCOME MEASURES: Atherosclerotic degree and blood flow volume of patients of two groups.RESULTS: Sixty patients with ischemic cerebrovascular disease and twenty subjects who received health examination participated in the final analysis. ①The IMT thickness, total plaque score, and total plaque area of patient group was significantly superior to that of control group, respectively( t=5.216 - 10.158, P 〈 0.05 ).② There were significant differences in the stenosis degree of CCA, ICA and VA between patient group and control group (t=6.720 - 12.816, P 〈 0.05 ) . ③ The blood flow volume of CCA, ICA, VA and brain of patient group was significantly lower than that of control group, respectively (t=2.872 - 10.860, P 〈 0.05).CONCLUSION: Ischemic cerebrovascular disease patients have different degrees of changes in atherosclerosis and arterial blood flow.
基金Supported by Beijing Municipal Commission of Education,Grant No.KM201110025026Projects of State Commission of Science and Technology of China,Grant No.2012BAI06B01Organ Transplantation Research Fund from the Ministry of Health,Grant No.RHECC08-2012-08
文摘We present a female patient with preterm labor, severe viral hepatitis B of acute phase, hepatic encephalopathy stage Ⅲ and coma.After delivery, the illness was exacerbated and the patient presented with clinical signs of vital organ dysfunctions such as acute respiratory distress syndrome, cerebral edema and hypoxemia that needed mechanical ventilation.Emergency liver transplantation was recommended after multidisciplinary panel consultations.The donor, her mother, consented to donate her right liver.Auxiliary partial orthotopic living donor liver transplantion(APOLDLT) was performed.After operation, the patient was on triple medication of tacrolimus plus mofetil mycophenolate and prednisone for immunosuppression.The combination of antihepatitis B virus(HBV) immunoglobulin and entecavir was initiated for anti-HBV therapy.Both the patient and the donor recovered well without any complications.The patient was followed up regularly.Her liver function, clinical signs and symptoms improved significantly.Until now, the recipient has been living for more than 78 mo free of any complications.The APOLDLT is a life-saving modality for rescuing patients with high-risk acute liver failure following HBV infection without available donor and hence is recommended under standardized antiviral therapy coverage as stated above.