Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datas...Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datasets GSE67066 and GSE60458.The R software and various packages were utilized for the analysis of differentially expressed genes,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,receiver operating characteristic curve assessment,logistic model construction,and correlation analysis.The NetworkAnalyst tool was used to analyze gene-miRNA interactions and signaling networks.In addition,the TIMER database was used to estimate the immune scores.Results:A total of 203 and 499 differentially expressed genes were identified in GSE67066 and GSE60458,respectively.These genes are implicated in cytokine and cytokine receptor interactions,extracellular matrix–receptor interactions,and platelet activation signaling pathways.Notably,MAMLD1,UST,MATN2,LPL,TWIST1,SFRP4,FRMD6,RBM24,PRIMA1,LYPD1,KCND2,CAMK2N1,SPOCK3,and ALPK3 were identified as the key genes.Among them,MATN2 and TWIST1 were found to be coexpressed with epithelial-mesenchymal transition–linked markers,whereas KCND2 and LPL exhibited associations with immune checkpoint expression and immune cell infiltration.Eight miRNAs were identified as potential regulators of key gene expression,and it was noted that TWIST1 might be regulated by SUZ12.Notably,the area under the curve of the 4-gene model for distinguishing between malignant and benign groups was calculated to be 0.918.Conclusions:The combined gene and mRNA expression model enhances the diagnostic accuracy of assessing PPGL metastatic potential.These findings suggest that multiple genes may play a role in the metastasis of PPGLs through the epithelial-mesenchymal transition and may influence the immune microenvironment.展开更多
Artificial Intelligence(AI)has increased as a potent tool in medicine,with promising oncology applications.The emergence of immunotherapy has transformed the treatment terrain for hepatocellular carcinoma(HCC),offerin...Artificial Intelligence(AI)has increased as a potent tool in medicine,with promising oncology applications.The emergence of immunotherapy has transformed the treatment terrain for hepatocellular carcinoma(HCC),offering new hope to patients with this challenging malignancy.This article examines the role and future of AI in forecasting the effectiveness of immunotherapy in HCC.We highlight the potential of AI to revolutionize the prediction of therapy response,thus improving patient selection and clinical outcomes.The article further outlines the challenges and future research directions in this emerging field.展开更多
Objectives: The purpose of this study was to evaluate and compare the use of propinox hydrochloride and scopolamine hydrochloride in patients presenting abdominal colic (abdominal pain), in terms of treatment efficacy...Objectives: The purpose of this study was to evaluate and compare the use of propinox hydrochloride and scopolamine hydrochloride in patients presenting abdominal colic (abdominal pain), in terms of treatment efficacy and tolerability. Material & Methods: This was an analytical, retrospective, comparative study based on hospital records of outpatients treated at Serviço de Clínica Médica do Hospital das Clínicas Costantino Otaviano (HCTCO) and at Santa Casa de Misericórdia do Rio de Janeiro, from 1988-1998. Subjects were divided into two groups: patients from Group 1 were treated with propinox hydrochloride, while patients from Group 2 were treated with scopolamine hydrochloride. Statistical analysis was performed using GraphPad Prism version 5.0. For comparison of categorical variables, we used the chi-squared or Fisher’s test, while continuous variables were analyzed using ANOVA or the Student’s T test. Results: A total of 1042 subjects were included, of which 525 were allocated to Group 1 and 517 to Group 2. Mean treatment duration was 9.166 days (±4.208) in Group 1 and 8.795 days (±5.052) in Group 2, with no statistically significant difference in treatment duration between the two groups (p = 0.198). All subjects in Group 1 were treated with propinox 10 mg (2 coated tablets, three times per day) while all subjects in Group 2 were treated with scopolamine hydrochloride 10 mg (2 coated tablets, three times per day). There were no statistically significant between-group differences in weight, BMI, heart rate, and respiratory rate at pre- and post-treatment;with the exception of higher post-treatment systolic blood pressure in Group 1, blood pressure measures also remained homogenous. Adverse events were reported among both treatment groups with no significant between-group difference in incidence (p = 0566). At pretreatment, pain intensity was more severe in Group 1 (p = 0.0257), while at post-treatment, there was no statistically significant difference between the two treatment groups (p = 0.895). There was a statistically significant improvement in pain intensity within both treatment groups (χ<sup>2</sup> = 631.4;df = 3;p < 0.0001 for Group 1 and χ<sup>2</sup> = 554.3;df = 3;p < 0.0001 for Group 2). Conclusion: The results obtained in this study indicate a therapeutic equivalence between propinox hydrochloride and scopolamine hydrochloride. Both treatments demonstrated good efficacy and tolerability in the treatment of abdominal colic pain, in the population evaluated.展开更多
AIM: To study the influence and mechanisms of dexamethasone on mesenteric lymph node of rats with severe acute pancreatitis (SAP). METHODS: The SAP rats were assigned to model, treated or sham-operated groups. The mor...AIM: To study the influence and mechanisms of dexamethasone on mesenteric lymph node of rats with severe acute pancreatitis (SAP). METHODS: The SAP rats were assigned to model, treated or sham-operated groups. The mortality, pathological changes of mesenteric lymph nodes, expression levels of NF-kB, P-selectin, Bax, Bcl-2 and caspase-3 protein and changes in apoptotic indexes in lymph nodes were observed at 3, 6 and 12 h after operation. The blood levels of endotoxin, superoxide dismutase (SOD), malondialdehyde (MDA), and endothelin-1 (ET-1) in blood were determined. RESULTS: SOD content, expression of Bax protein and apoptotic index were significantly higher in the treated group than in the model group at different time points (P < 0.05 or P < 0.01). Other blood-detecting indexes and histopathological scores of mesenteric lymphnodes were lower in the treated than in the model group (P < 0.05, P < 0.01 or P < 0.01). NF-kB protein expression was negative in all groups. Comparing P-selectin and caspase-3 expression levels among all three groups, there was no marked difference between the model and treated group. CONCLUSION: Dexamethasone can protect mesen-teric lymph nodes. The mechanism may be by reducing the content of inflammatory mediators in the blood and inducing lymphocyte apoptosis.展开更多
AIM To perform a systematic review to evaluate the incidence and prevalence of non-alcoholic fatty liver disease(NAFLD) in adult patients with sarcopenia.METHODS Randomized clinical trials,cross-sectional or cohort st...AIM To perform a systematic review to evaluate the incidence and prevalence of non-alcoholic fatty liver disease(NAFLD) in adult patients with sarcopenia.METHODS Randomized clinical trials,cross-sectional or cohort studies including adult patients(over 18 years) with sarcopenia were selected.The primary outcomes of interest were the prevalence or incidence of NAFLD in sarcopenic patients.In the screening process,44 fulltext articles were included in the review and 41 studies were excluded.RESULTS Three cross-sectional studies were included.The authors attempted to perform a systematic review,but due to the differences between the studies,a qualitative synthesis was provided.The diagnosis of NAFLD was made by non-invasive methods(image methods or any surrogate markers) in all three evaluated studies.All the studies suggested that there was an independent association between sarcopenia and NAFLD.CONCLUSION Sarcopenia is independently associated with NAFLD and possibly to an advanced fibrosis.展开更多
Dual hepatitis C virus(HCV)/hepatitis B virus(HBV)infection is found in HBV or HCV endemic areas,and in specific populations exhibiting a high risk of parenteral viral transmission.Clinical observations have revealed ...Dual hepatitis C virus(HCV)/hepatitis B virus(HBV)infection is found in HBV or HCV endemic areas,and in specific populations exhibiting a high risk of parenteral viral transmission.Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients.The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations.Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections.Strikingly,approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV.The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined.Furthermore,approximately 30%of dually infected patients lost hepatitis B surface antigen(HBsAg)within 5 years after the start of peginterferonbased therapy,and 40%of them harbored occult HBV infection.The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations.Moreover,the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored.Finally,the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future,which warrants further clinical trials.展开更多
Cytomegalovirus(CMV)infection of the gastrointestinal (GI)tract has been reported in both immunocompetent and,more frequently,in immunocompromised patients.We describe a case of a 19-year-old male who developed CMV in...Cytomegalovirus(CMV)infection of the gastrointestinal (GI)tract has been reported in both immunocompetent and,more frequently,in immunocompromised patients.We describe a case of a 19-year-old male who developed CMV infection of the terminal ileum while receiving immunosuppression for lupus nephritis. This was a distinctly unusual site of infection which clinically mimicked Crohn's ileitis.We note that reports of terminal ileal CMV infection have been infrequent. Despite a complicated hospital course,ganciclovir therapy was effective in resolving his symptoms and normalizing his ileal mucosa.This report highlights the importance of accurate histological diagnosis and clinical follow-up of lupus patients with GI symptoms undergoing intense immunosuppression.展开更多
OBJECTIVE: Studies on the repair of peripheral nerve injury have achieved great progresses in recent years.Clinical nerve repair prefers microsurgery, while fundamental researches focus on tissue engineering and gene...OBJECTIVE: Studies on the repair of peripheral nerve injury have achieved great progresses in recent years.Clinical nerve repair prefers microsurgery, while fundamental researches focus on tissue engineering and gene therapy. Recently, microencapsulation technique rises up as a new treatment therapy. This article mainly summarized the repairing techniques referred above, in order to make the basis for further research.DATA SOURCES: A computer-based online search of Pubmed database was undertaken to identify articles about injury and repair of peripheral nerve published in English between January 1997 and May 2007 using the key words of "peripheral nerve, injury, repair". At the same time, Chinese relative articles were searched in China National Knowledge Infrastructure (CNKI) using the same key words in Chinese.STUDY SELECTION: The data were primarily checked, and the references after each literature were looked up, and the articles focused on the injury and repair of peripheral nerve were selected. Those published in kola-magazine in recent 5 years were in priority for the articles with similar contents. Repetitive studies or Meta analysis were excluded.DATA EXTRACTION: Totally 144 articles were collected, and 30 literatures were selected as most relative reference literatures, and the other 114 articles were excluded due to old or repeated researches. Among the 30 selected articles, 6 focused on the surgical treatment for peripheral nerve injury, 10 on tissue engineering and Schwann cell, 3 on microencapsulation technology, 5 on gene therapy, 2 on immunosuppresant and 4 on neurotrophic factors.DATA SYNTHESIS: The technologies for repairing peripheral nerve injury are developing with time, also have been successfully combined with tissue engineering and gene therapy techniques which are advanced nowadays. As the researches go further, immunodepression factors have attracted more and more attentions,microencapsulation technology and gene therapy repair also go into the view of researchers. The main aim of technique referred above is to recover the physiological structure and function as much as possible. However,the clinical applications have a long way to go for the series of restrictions from the problems of rejection, etc.The clinical repair of peripheral nerve injury still mainly depends on microscopic neurorrhaphy and nerve grafting at present, whereas the satisfying repair techniques are waiting for more professional researches.CONCLUSION: Restricted by techniques, microsurgery repair is still the first choice for peripheral nerve injury. Microencapsulation technique and gene therapy offer a new direction for peripheral nerve repair;tissue engineering gains great success in animal experiment together have wide prospect on clinical application, many problems wait for solution though, they will be point of following researches.展开更多
BACKGROUND Nonalcoholic steatohepatitis-related cirrhosis is one of the liver complications in type 2 diabetes mellitus(T2DM)and reported to be a risk factor for developing hepatocellular carcinoma(HCC).A reliable scr...BACKGROUND Nonalcoholic steatohepatitis-related cirrhosis is one of the liver complications in type 2 diabetes mellitus(T2DM)and reported to be a risk factor for developing hepatocellular carcinoma(HCC).A reliable screening biomarker of liver cirrhosis(LC)and HCC among T2DM patients is important to reduce the morbidity and mortality of this disease.MicroRNA(miRNA)is considered a key player in HCC and T2DM,and it might be a hidden culprit in diabetes-associated HCC,making it a promising reliable prognostic tool.AIM To investigate the signature of serum miRNAs as early biomarkers for the screening of HCC among diabetic patients.METHODS Expression profiles of miRNAs in serum samples of diabetic LC and diabetic HCC patients were assessed using Illumina sequencing;then,RT-qPCR was used to validate significantly altered miRNAs between the two groups.Candidate miRNAs were tested in serum samples of 200 T2DM patients,270 LC patients,200 HCC patients,and 225 healthy control subjects.Additionally,receiver operating characteristic(ROC)analysis,with area under the curve(AUC),was performed to assess the diagnostic performance of the screened miRNAs for discriminating HCC from LC and nonmalignant patients(LC+T2DM).RESULTS Expression of the sequenced miRNAs in serum was different in HCC vs LCpositive T2DM patients.Two miRNAs(miR-34a,miR-221)were significantly upregulated and five miRNAs(miR-16,miR-23-3p,miR-122-5p,miR-198,miR-199a-3p)were significantly down-regulated in HCC compared to LC patients.Analysis of ROC curve demonstrated that the combination of these seven miRNAs can be used as a reliable biomarker for detection of HCC in diabetic patients,as it could identify HCC with high diagnostic accuracy in diabetic LC patients(AUC=0.993)and in diabetic nonmalignant patients(AUC=0.961).CONCLUSION This study validates a panel of serum miRNAs that can be used as a reliable noninvasive screening biomarker of HCC among T2DM cirrhotic and noncirrhotic patients.The study recommends further research to shed light on a possible role of c-Met in T2DM-associated HCC via the miRNA regulatory pathway.展开更多
OBJECTIVE The purpose of this study is to clarify the association between Cu levels and heart failure(HF)using a meta-analysis approach.METHODS We searched articles in the Pub Med,EMbase,CNKI,Wanfang,VIP and CBM Datab...OBJECTIVE The purpose of this study is to clarify the association between Cu levels and heart failure(HF)using a meta-analysis approach.METHODS We searched articles in the Pub Med,EMbase,CNKI,Wanfang,VIP and CBM Database published as of August 2016.The case control study on the relationship between serum copper levels and HF were collected and read and extracted by two independent researchers.A Meta analysis was conducted using Stata 12.0 software.RESULTS A total of twenty-one eligible articles,including 893 HF and 654 control subjects,were enrolled.The Meta analysis showed that serum copper levels in HF were higher than control group[SMD=0.881,95%CI:(0.487,1.264),Z=4.5,P<0.001].The sensitivity analysis indicated that the results were reliable.Begg′s tests did not find the existence of publication bias.CONCLUSION This metaanalysis indicates that there is a significant association between high Cu serum level and HF.展开更多
Difference in environmental condition shapes variation in digestive tract length in evolutionary process.In particular,environmental difference results in variation in food resource among different habitats,and thereb...Difference in environmental condition shapes variation in digestive tract length in evolutionary process.In particular,environmental difference results in variation in food resource among different habitats,and thereby affecting energy intake and energy allocation.The digestive theory predicts that animals foraging high indigestible materials of stomach contents can promote the increased gut dimensions.Here,we studied variation in digestive tract and gut length across six Hylarana guentheri populations at different altitudes and latitudes to test the prediction of the digestive theory.We found that altitude and latitude did not affect variation in relative size of digestive tract and gut among populations.We also found that relative size of digestive tract and gut did not be correlated with diversity of prey items,but negatively correlated with proportion of digestible materials.Our findings suggest that individuals foraging less digestible materials display relatively longer digestive tract than individuals foraging more digestible materials.展开更多
Macrophages are important antigen-presenting cells to combat tumor via both innate and adaptive immunity,while they are programmed toM2 phenotype in established tumors and instead promote cancer development and metast...Macrophages are important antigen-presenting cells to combat tumor via both innate and adaptive immunity,while they are programmed toM2 phenotype in established tumors and instead promote cancer development and metastasis.Here,we develop a nanomedicine that can re-educate M2 polarized macrophages to restore their anti-tumor activities.The nanomedicine has a core-shell structure to co-load IPI549,a PI3Kγinhibitor,and CpG,a Toll-like receptor 9 agonist.Specifically,the hydrophobic IPI549 is self-assembled into a pure drug nano-core,while MOF shell layer is coated for CpG encapsulation,achieving extra-high total drugs loading of 44%.Such nanosystem could facilitate intracellular delivery of the payloads but without any cytotoxicity,displaying excellent biocompatibility.After entering macrophages,the released IPI549 and CpG exert a synergistic effect to switch macrophages from M2 to M1 phenotype,which enables anti-tumor activities via directly engulfing tumor cells or excreting tumor killing cytokines.Moreover,tumor antigens released from the dying tumor cells could be effectively presented by the re-educated macrophages owing to the up-regulation of various antigen presenting mediators,resulting in infiltration and activation of cytotoxic T lymphocytes.As a result,the nanosystem triggers a robust antitumor immune response in combination with PD-L1 antibody to inhibit tumor growth and metastasis.This work provides a non-cytotoxic nanomedicine to modulate tumor immune microenvironment by reprograming macrophages.展开更多
Objective Although benzene is a confirmed environmental carcinogen,the mechanism of its carcinogenicity remains largely unclear.The suggested oncogene,miR-221,is elevated and plays important roles in various tumors,bu...Objective Although benzene is a confirmed environmental carcinogen,the mechanism of its carcinogenicity remains largely unclear.The suggested oncogene,miR-221,is elevated and plays important roles in various tumors,but its role in benzene-induced carcinogenesis remains unknown.Methods In the present study,we constructed hydroquinone(HQ,a representative metabolite of benzene with biological activity)-transformed malignant cell line(16 HBE-t)and analyzed the level of miR-221 in it with qRT-PCR.Exosomes from 16 HBE-t cells incubated with or without an miR-221 inhibitor were isolated by ultracentrifugation,characterized by transmission electron microscopy and laser scanning confocal microscope,and then transfected into 16 HBE cells.The effects of exosomal miR-221 on apoptosis induced by HQ in recipient cells were determined using flow cytometry.Results The amount of miR-221 in 16 HBE-t was significantly increased compared with controls.When recipient cells ingested exosomes derived from 16 HBE-t,miR-221 was increased,and apoptosis induced by HQ was inhibited.Blocking miR-221 in 16 HBE-t using an inhibitor did not significantly alter miR-221 or apoptosis in recipient cells.Conclusion Exosomal miR-221 secreted by 16 HBE-t inhibits apoptosis induced by HQ in normal recipient cells.展开更多
Objective:to explore the changes of the F-wave in the posterior tibial nerve of rabbits after different levels of lumbar spinal cord ischaemic injury and its correlation with motor function and the extent of lumbar sp...Objective:to explore the changes of the F-wave in the posterior tibial nerve of rabbits after different levels of lumbar spinal cord ischaemic injury and its correlation with motor function and the extent of lumbar spinal cord pathological damage.Methods:thirty New Zealand rabbits were randomly divided into 6 groups.The control group(n=5)was used to exclude the influence of anaesthesia and surgery on the F-wave.Different levels of lumbar arteries were ligated in the five experimental groups(n=5).The F-wave was recorded to observe the changes in the acute phase of spinal cord ischaemia.The correlation between the changes of the F-wave in the acute reversible phase and the motor function of the spinal cord was analysed.Motor functions were assessed after surgery and 2 d after vascular ligation.The specimens were taken 2 d after ligation for histopathologic observation.Results:the results for the control group indicated that anaesthesia and surgery did not affect the F-wave results.There was no statistically significant difference in the F-wave amplitudes and latency before and after ligation in the 1 and 2 level ligation groups.The F-wave changed immediately after ligation in the 3,4 and 5 ligation groups.The latency of the F-wave gradually extended,the amplitude of the F-wave gradually reduced.The amplitude variations of the F-wave were positively correlated with the motor function 2 d after ligation,there was a statistically significant difference.With the increase in the number of vascular ligation,the degree of destruction of the motor neurons in the anterior horn of the spinal cord in the pathological specimens increased.Conclusion:the F-waves in the posterior tibial nerve of rabbits were found to be sensitive to the lumbar spinal cord ischaemic injury and specific to predict motor function.展开更多
Dear Editor,Recently,a number of new Omicron subvariants related to BA.4/5 and BA.2.75 have emerged and shown remarkable antibody evasion capacities,in particular BF.7,BQ.1,BQ.1.1,BA.2.75.2,XBB and XBB.1.5.1 Unsurpris...Dear Editor,Recently,a number of new Omicron subvariants related to BA.4/5 and BA.2.75 have emerged and shown remarkable antibody evasion capacities,in particular BF.7,BQ.1,BQ.1.1,BA.2.75.2,XBB and XBB.1.5.1 Unsurprisingly,these new subvariants are quickly gaining prevalence worldwide.In fact,some of them have outcompeted BA.5 in the USA according to CDC’s national genomic surveillance data in which,as of 6th February 2023,XBB.1.5,BQ.1.1,BQ.1,XBB and BF.7 have achieved a dominance of 66.4%,19.9%,7.3%,2.3%and 0.5%in the USA,as compared to 0.5%for BA.5.In this report,using plasma samples collected from individuals following different vaccination strategies and COVID-19 convalescent donors,we performed pseudoviral neutralization assays to confirm severe reductions in neutralization titers against BF.7,BQ.1,BQ.1.1,BA.2.75.2,XBB and XBB.1.5 in comparison to other Omicron sub-lineages.XBB and XBB.1.5 were shown to be remarkably resistant to plasma neutralization in all tested cohorts.By comparing the differential neutralization profiles,we found that a heterologous booster with an aerosolized vaccine following 2 doses of inactivated vaccine seemed to be superior to other vaccination strategies.展开更多
Homologous booster,heterologous booster,and Omicron variants breakthrough infection(OBI)could improve the humoral immunity against Omicron variants.Questions concerning about memory B cells(MBCs)and T cells immunity a...Homologous booster,heterologous booster,and Omicron variants breakthrough infection(OBI)could improve the humoral immunity against Omicron variants.Questions concerning about memory B cells(MBCs)and T cells immunity against Omicron variants,features of long-term immunity,after booster and OBI,needs to be explored.Here,comparative analysis demonstrate antibody and T cell immunity against ancestral strain,Delta and Omicron variants in Omicron breakthrough infected patients(OBIPs)are comparable to that in Ad5-nCoV boosted healthy volunteers(HVs),higher than that in inactivated vaccine(InV)boosted HVs.However,memory B cells(MBCs)immunity against Omicron variants was highest in OBIPs,followed by Ad5-nCoV boosted and InV boosted HVs.OBIPs and Ad5-nCoV boosted HVs have higher classical MBCs and activated MBCs,and lower naïve MBCs and atypical MBCs relative to both vaccine boosted HVs.Collectively,these data indicate Omicron breakthrough infection elicit higher MBCs and T cells against SARS-CoV-2 especially Omicron variants relative to homologous InV booster and heterologous Ad5-nCoV booster.展开更多
In heart disease, transforming growth factor-β1 (TGF-β1) converts fibroblasts into myofibroblasts, which synthesize and se- crete fibrillar type I and III collagens. The purpose of the present study was to investi...In heart disease, transforming growth factor-β1 (TGF-β1) converts fibroblasts into myofibroblasts, which synthesize and se- crete fibrillar type I and III collagens. The purpose of the present study was to investigate how hydrogen sulfide (HzS) sup- presses TGF-~l-induced differentiation of human cardiac fibroblasts to myofibroblasts. Human cardiac fibroblasts were se- rum-starved in fibroblast medium for 16 h before exposure to TGF-β1 (10 ng mL-1) for 24 h with or without sodium hydrosul- fide (NariS, 100 μmol L-1, 30 min pretreatment) treatment. NariS, an exogenous HzS donor, potently inhibited the prolifera- tion and migration of TGF-β1-induced human cardiac fibroblasts and regulated their cell cycle progression. Furthermore, NariS treatment led to suppression of fibroblast differentiation into myofibroblasts, and reduced the levels of collagen, TGF-β1, and activated Smad3 in TGF-β1-induced human cardiac fibroblasts in vitro. We therefore conclude that H2S sup- presses TGF-β1-stimulated conversion of fibroblasts to myofibroblasts by inhibiting the TGF-β1/Smad3 signaling pathway, as well as by inhibiting the proliferation, migration, and cell cycle progression of human cardiac myofibroblasts. These effects of H2S may play significant roles in cardiac remodeling associated with heart failure.展开更多
Background Neonatal hyperbilirubinemia is observed in most newborns,and 5–15%of neonates require phototherapy.Phototherapy is efective but often prolongs hospitalization and has both short-term and potential long-ter...Background Neonatal hyperbilirubinemia is observed in most newborns,and 5–15%of neonates require phototherapy.Phototherapy is efective but often prolongs hospitalization and has both short-term and potential long-term harms.The aim of this systematic review and meta-analysis was to evaluate the role of ursodeoxycholic acid(UDCA)combined with phototherapy in neonatal hyperbilirubinemia.Methods A literature search was conducted on September 1,2021;590 studies were screened,and 17 full texts were assessed by two authors.We included randomized controlled trials with or without placebo intervention.Primary outcomes were changes in total bilirubin levels at 24 hours and phototherapy duration.We calculated mean diferences with 95%confdence intervals(CI).Results Six studies with 880 neonates were included.Of these studies,only two used a placebo-controlled double-blinded design.The overall risk of bias was high in one and moderate in four of the included studies.The mean decrease in the total bilirubin level during the frst 24 hours was 2.06 mg/dL(95%CI 0.82–3.30;six studies)greater in the UDCA treatment group.The phototherapy duration was 19.7 hours(95%CI 10.4–29.1;fve studies)shorter in the UDCA treatment group.Conclusions We found low-quality evidence that UDCA as an adjuvant to phototherapy seems to decrease total bilirubin faster and shorten phototherapy duration compared to standard treatment.Further studies are needed to confrm the efcacy,acute and long-term outcomes,and safety before implementing UDCA as an adjuvant to phototherapy in neonatal hyperbilirubinemia.展开更多
Worldwide incidence of hepatocellular carcinoma (HCC) is steadily increasing,highlighting its status as a public health concern,particularly due to its significant association with other comorbidities,such as diabetes...Worldwide incidence of hepatocellular carcinoma (HCC) is steadily increasing,highlighting its status as a public health concern,particularly due to its significant association with other comorbidities,such as diabetes.However,nonalcoholic fatty liver disease (NAFLD) has emerged as a primary risk factor,with its own prevalence increasing in recent years,and it has gradually caught up with the historical primary etiological factors of infection with hepatitis B virus and hepatitis C virus,exposure to aflatoxin,or alcohol liver disease.The deeply worrisome aspects of all of these high risk factors,however,are their remarkable presence within populations.Systemic and genetic mechanisms involved in the malignant transformation of liver cells,as well as useful biomarkers of early stage HCC are being investigated.However,the exact mechanisms underlying the interrelation of NAFLD and HCC remain largely unknown.In this review,some of the recent advances in our understanding of liver lipid accumulation are summarized and discussed to provide insights into the relationship between NAFLD and hepatocyte malignant transformation.(C) 2016 The Second Affiliated Hospital of Chongqing Medical University.Published by XIA & HE Publishing Inc.All rights reserved.展开更多
基金supported by the Project of the 940 Hospital of the Joint Logistics Support Force of the Chinese PLA(no.2021yxky057).
文摘Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datasets GSE67066 and GSE60458.The R software and various packages were utilized for the analysis of differentially expressed genes,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,receiver operating characteristic curve assessment,logistic model construction,and correlation analysis.The NetworkAnalyst tool was used to analyze gene-miRNA interactions and signaling networks.In addition,the TIMER database was used to estimate the immune scores.Results:A total of 203 and 499 differentially expressed genes were identified in GSE67066 and GSE60458,respectively.These genes are implicated in cytokine and cytokine receptor interactions,extracellular matrix–receptor interactions,and platelet activation signaling pathways.Notably,MAMLD1,UST,MATN2,LPL,TWIST1,SFRP4,FRMD6,RBM24,PRIMA1,LYPD1,KCND2,CAMK2N1,SPOCK3,and ALPK3 were identified as the key genes.Among them,MATN2 and TWIST1 were found to be coexpressed with epithelial-mesenchymal transition–linked markers,whereas KCND2 and LPL exhibited associations with immune checkpoint expression and immune cell infiltration.Eight miRNAs were identified as potential regulators of key gene expression,and it was noted that TWIST1 might be regulated by SUZ12.Notably,the area under the curve of the 4-gene model for distinguishing between malignant and benign groups was calculated to be 0.918.Conclusions:The combined gene and mRNA expression model enhances the diagnostic accuracy of assessing PPGL metastatic potential.These findings suggest that multiple genes may play a role in the metastasis of PPGLs through the epithelial-mesenchymal transition and may influence the immune microenvironment.
基金Supported by the National Natural Science Foundation of China,No.81401988China Postdoctoral Science Foundation,No.2019M661907+4 种基金Jiangsu Postdoctoral Science Foundation,No.2019K159,and No.2019Z153General Project of Jiangsu Provincial Health Committee,No.H2023136General Project of Nantong Municipal Health Committee,No.MS2023013Jiangsu Provincial Research Hospital,No.YJXYY202204-YSB28and College Student Innovation Program,No.202210304128Y,and No.2023103041055.
文摘Artificial Intelligence(AI)has increased as a potent tool in medicine,with promising oncology applications.The emergence of immunotherapy has transformed the treatment terrain for hepatocellular carcinoma(HCC),offering new hope to patients with this challenging malignancy.This article examines the role and future of AI in forecasting the effectiveness of immunotherapy in HCC.We highlight the potential of AI to revolutionize the prediction of therapy response,thus improving patient selection and clinical outcomes.The article further outlines the challenges and future research directions in this emerging field.
文摘Objectives: The purpose of this study was to evaluate and compare the use of propinox hydrochloride and scopolamine hydrochloride in patients presenting abdominal colic (abdominal pain), in terms of treatment efficacy and tolerability. Material & Methods: This was an analytical, retrospective, comparative study based on hospital records of outpatients treated at Serviço de Clínica Médica do Hospital das Clínicas Costantino Otaviano (HCTCO) and at Santa Casa de Misericórdia do Rio de Janeiro, from 1988-1998. Subjects were divided into two groups: patients from Group 1 were treated with propinox hydrochloride, while patients from Group 2 were treated with scopolamine hydrochloride. Statistical analysis was performed using GraphPad Prism version 5.0. For comparison of categorical variables, we used the chi-squared or Fisher’s test, while continuous variables were analyzed using ANOVA or the Student’s T test. Results: A total of 1042 subjects were included, of which 525 were allocated to Group 1 and 517 to Group 2. Mean treatment duration was 9.166 days (±4.208) in Group 1 and 8.795 days (±5.052) in Group 2, with no statistically significant difference in treatment duration between the two groups (p = 0.198). All subjects in Group 1 were treated with propinox 10 mg (2 coated tablets, three times per day) while all subjects in Group 2 were treated with scopolamine hydrochloride 10 mg (2 coated tablets, three times per day). There were no statistically significant between-group differences in weight, BMI, heart rate, and respiratory rate at pre- and post-treatment;with the exception of higher post-treatment systolic blood pressure in Group 1, blood pressure measures also remained homogenous. Adverse events were reported among both treatment groups with no significant between-group difference in incidence (p = 0566). At pretreatment, pain intensity was more severe in Group 1 (p = 0.0257), while at post-treatment, there was no statistically significant difference between the two treatment groups (p = 0.895). There was a statistically significant improvement in pain intensity within both treatment groups (χ<sup>2</sup> = 631.4;df = 3;p < 0.0001 for Group 1 and χ<sup>2</sup> = 554.3;df = 3;p < 0.0001 for Group 2). Conclusion: The results obtained in this study indicate a therapeutic equivalence between propinox hydrochloride and scopolamine hydrochloride. Both treatments demonstrated good efficacy and tolerability in the treatment of abdominal colic pain, in the population evaluated.
基金Technological Foundation Project of Traditional Chinese Medicine Science of Zhejiang Province, No. 2003C130 and No. 2004C142Foundation Project for Medical Science and Technology of Zhejiang Province, No. 2003B134+5 种基金Grave Foundation Project for Technological and Development of Hangzhou, No. 2003123B19Intensive Foundation Project for Technology of Hangzhou No. 2004Z006Foundation Project for Medical Science and Technology of Hangzhou No. 2003A004Foundation Project for Technology of Hangzhou, No. 2005224
文摘AIM: To study the influence and mechanisms of dexamethasone on mesenteric lymph node of rats with severe acute pancreatitis (SAP). METHODS: The SAP rats were assigned to model, treated or sham-operated groups. The mortality, pathological changes of mesenteric lymph nodes, expression levels of NF-kB, P-selectin, Bax, Bcl-2 and caspase-3 protein and changes in apoptotic indexes in lymph nodes were observed at 3, 6 and 12 h after operation. The blood levels of endotoxin, superoxide dismutase (SOD), malondialdehyde (MDA), and endothelin-1 (ET-1) in blood were determined. RESULTS: SOD content, expression of Bax protein and apoptotic index were significantly higher in the treated group than in the model group at different time points (P < 0.05 or P < 0.01). Other blood-detecting indexes and histopathological scores of mesenteric lymphnodes were lower in the treated than in the model group (P < 0.05, P < 0.01 or P < 0.01). NF-kB protein expression was negative in all groups. Comparing P-selectin and caspase-3 expression levels among all three groups, there was no marked difference between the model and treated group. CONCLUSION: Dexamethasone can protect mesen-teric lymph nodes. The mechanism may be by reducing the content of inflammatory mediators in the blood and inducing lymphocyte apoptosis.
文摘AIM To perform a systematic review to evaluate the incidence and prevalence of non-alcoholic fatty liver disease(NAFLD) in adult patients with sarcopenia.METHODS Randomized clinical trials,cross-sectional or cohort studies including adult patients(over 18 years) with sarcopenia were selected.The primary outcomes of interest were the prevalence or incidence of NAFLD in sarcopenic patients.In the screening process,44 fulltext articles were included in the review and 41 studies were excluded.RESULTS Three cross-sectional studies were included.The authors attempted to perform a systematic review,but due to the differences between the studies,a qualitative synthesis was provided.The diagnosis of NAFLD was made by non-invasive methods(image methods or any surrogate markers) in all three evaluated studies.All the studies suggested that there was an independent association between sarcopenia and NAFLD.CONCLUSION Sarcopenia is independently associated with NAFLD and possibly to an advanced fibrosis.
基金Supported by Grants from the National Taiwan UniversityDe-partment of Health,Executive Yuan,TaiwanTaiwan Liver Disease Consortium(TLC),National Research Program for Bio-pharmaceuticals(NRPB),Taiwan,NSC100-2325-B-002-052
文摘Dual hepatitis C virus(HCV)/hepatitis B virus(HBV)infection is found in HBV or HCV endemic areas,and in specific populations exhibiting a high risk of parenteral viral transmission.Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients.The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations.Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections.Strikingly,approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV.The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined.Furthermore,approximately 30%of dually infected patients lost hepatitis B surface antigen(HBsAg)within 5 years after the start of peginterferonbased therapy,and 40%of them harbored occult HBV infection.The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations.Moreover,the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored.Finally,the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future,which warrants further clinical trials.
文摘Cytomegalovirus(CMV)infection of the gastrointestinal (GI)tract has been reported in both immunocompetent and,more frequently,in immunocompromised patients.We describe a case of a 19-year-old male who developed CMV infection of the terminal ileum while receiving immunosuppression for lupus nephritis. This was a distinctly unusual site of infection which clinically mimicked Crohn's ileitis.We note that reports of terminal ileal CMV infection have been infrequent. Despite a complicated hospital course,ganciclovir therapy was effective in resolving his symptoms and normalizing his ileal mucosa.This report highlights the importance of accurate histological diagnosis and clinical follow-up of lupus patients with GI symptoms undergoing intense immunosuppression.
基金the CollegeFoundation of Education Bureau of Liaoning Province,No.05L44a
文摘OBJECTIVE: Studies on the repair of peripheral nerve injury have achieved great progresses in recent years.Clinical nerve repair prefers microsurgery, while fundamental researches focus on tissue engineering and gene therapy. Recently, microencapsulation technique rises up as a new treatment therapy. This article mainly summarized the repairing techniques referred above, in order to make the basis for further research.DATA SOURCES: A computer-based online search of Pubmed database was undertaken to identify articles about injury and repair of peripheral nerve published in English between January 1997 and May 2007 using the key words of "peripheral nerve, injury, repair". At the same time, Chinese relative articles were searched in China National Knowledge Infrastructure (CNKI) using the same key words in Chinese.STUDY SELECTION: The data were primarily checked, and the references after each literature were looked up, and the articles focused on the injury and repair of peripheral nerve were selected. Those published in kola-magazine in recent 5 years were in priority for the articles with similar contents. Repetitive studies or Meta analysis were excluded.DATA EXTRACTION: Totally 144 articles were collected, and 30 literatures were selected as most relative reference literatures, and the other 114 articles were excluded due to old or repeated researches. Among the 30 selected articles, 6 focused on the surgical treatment for peripheral nerve injury, 10 on tissue engineering and Schwann cell, 3 on microencapsulation technology, 5 on gene therapy, 2 on immunosuppresant and 4 on neurotrophic factors.DATA SYNTHESIS: The technologies for repairing peripheral nerve injury are developing with time, also have been successfully combined with tissue engineering and gene therapy techniques which are advanced nowadays. As the researches go further, immunodepression factors have attracted more and more attentions,microencapsulation technology and gene therapy repair also go into the view of researchers. The main aim of technique referred above is to recover the physiological structure and function as much as possible. However,the clinical applications have a long way to go for the series of restrictions from the problems of rejection, etc.The clinical repair of peripheral nerve injury still mainly depends on microscopic neurorrhaphy and nerve grafting at present, whereas the satisfying repair techniques are waiting for more professional researches.CONCLUSION: Restricted by techniques, microsurgery repair is still the first choice for peripheral nerve injury. Microencapsulation technique and gene therapy offer a new direction for peripheral nerve repair;tissue engineering gains great success in animal experiment together have wide prospect on clinical application, many problems wait for solution though, they will be point of following researches.
基金support from the National Research Centre (Cairo, Egypt), Medical Research Institute (Alexandria, Egypt) and Korea Institute of Science and Technology (Republic of Korea, 2Z05620)
文摘BACKGROUND Nonalcoholic steatohepatitis-related cirrhosis is one of the liver complications in type 2 diabetes mellitus(T2DM)and reported to be a risk factor for developing hepatocellular carcinoma(HCC).A reliable screening biomarker of liver cirrhosis(LC)and HCC among T2DM patients is important to reduce the morbidity and mortality of this disease.MicroRNA(miRNA)is considered a key player in HCC and T2DM,and it might be a hidden culprit in diabetes-associated HCC,making it a promising reliable prognostic tool.AIM To investigate the signature of serum miRNAs as early biomarkers for the screening of HCC among diabetic patients.METHODS Expression profiles of miRNAs in serum samples of diabetic LC and diabetic HCC patients were assessed using Illumina sequencing;then,RT-qPCR was used to validate significantly altered miRNAs between the two groups.Candidate miRNAs were tested in serum samples of 200 T2DM patients,270 LC patients,200 HCC patients,and 225 healthy control subjects.Additionally,receiver operating characteristic(ROC)analysis,with area under the curve(AUC),was performed to assess the diagnostic performance of the screened miRNAs for discriminating HCC from LC and nonmalignant patients(LC+T2DM).RESULTS Expression of the sequenced miRNAs in serum was different in HCC vs LCpositive T2DM patients.Two miRNAs(miR-34a,miR-221)were significantly upregulated and five miRNAs(miR-16,miR-23-3p,miR-122-5p,miR-198,miR-199a-3p)were significantly down-regulated in HCC compared to LC patients.Analysis of ROC curve demonstrated that the combination of these seven miRNAs can be used as a reliable biomarker for detection of HCC in diabetic patients,as it could identify HCC with high diagnostic accuracy in diabetic LC patients(AUC=0.993)and in diabetic nonmalignant patients(AUC=0.961).CONCLUSION This study validates a panel of serum miRNAs that can be used as a reliable noninvasive screening biomarker of HCC among T2DM cirrhotic and noncirrhotic patients.The study recommends further research to shed light on a possible role of c-Met in T2DM-associated HCC via the miRNA regulatory pathway.
文摘OBJECTIVE The purpose of this study is to clarify the association between Cu levels and heart failure(HF)using a meta-analysis approach.METHODS We searched articles in the Pub Med,EMbase,CNKI,Wanfang,VIP and CBM Database published as of August 2016.The case control study on the relationship between serum copper levels and HF were collected and read and extracted by two independent researchers.A Meta analysis was conducted using Stata 12.0 software.RESULTS A total of twenty-one eligible articles,including 893 HF and 654 control subjects,were enrolled.The Meta analysis showed that serum copper levels in HF were higher than control group[SMD=0.881,95%CI:(0.487,1.264),Z=4.5,P<0.001].The sensitivity analysis indicated that the results were reliable.Begg′s tests did not find the existence of publication bias.CONCLUSION This metaanalysis indicates that there is a significant association between high Cu serum level and HF.
基金Financial support was provided by the National Natural Sciences Foundation of China(31772451,31970393)the Science and Technology Youth Innovation Team of Sichuan Province(19CXTD0022)+1 种基金the Key Cultivation Foundation of China West Normal University(17A006)Talent Project of China West Normal University(17YC335)。
文摘Difference in environmental condition shapes variation in digestive tract length in evolutionary process.In particular,environmental difference results in variation in food resource among different habitats,and thereby affecting energy intake and energy allocation.The digestive theory predicts that animals foraging high indigestible materials of stomach contents can promote the increased gut dimensions.Here,we studied variation in digestive tract and gut length across six Hylarana guentheri populations at different altitudes and latitudes to test the prediction of the digestive theory.We found that altitude and latitude did not affect variation in relative size of digestive tract and gut among populations.We also found that relative size of digestive tract and gut did not be correlated with diversity of prey items,but negatively correlated with proportion of digestible materials.Our findings suggest that individuals foraging less digestible materials display relatively longer digestive tract than individuals foraging more digestible materials.
基金supported by National Natural Science Foundation of China (Nos. 21804144, 81974000, U1903125, 82073799)Natural Science Foundation of Hunan province in China (Nos. 2021JJ10077, 2021JJ20084, 2022JJ30903)+1 种基金Natural Science Foundation of Changsha City in Hunan province,China (No. kq2202421)the Science and Technology Innovation Program of Hunan Province (No. 2021RC3020)
文摘Macrophages are important antigen-presenting cells to combat tumor via both innate and adaptive immunity,while they are programmed toM2 phenotype in established tumors and instead promote cancer development and metastasis.Here,we develop a nanomedicine that can re-educate M2 polarized macrophages to restore their anti-tumor activities.The nanomedicine has a core-shell structure to co-load IPI549,a PI3Kγinhibitor,and CpG,a Toll-like receptor 9 agonist.Specifically,the hydrophobic IPI549 is self-assembled into a pure drug nano-core,while MOF shell layer is coated for CpG encapsulation,achieving extra-high total drugs loading of 44%.Such nanosystem could facilitate intracellular delivery of the payloads but without any cytotoxicity,displaying excellent biocompatibility.After entering macrophages,the released IPI549 and CpG exert a synergistic effect to switch macrophages from M2 to M1 phenotype,which enables anti-tumor activities via directly engulfing tumor cells or excreting tumor killing cytokines.Moreover,tumor antigens released from the dying tumor cells could be effectively presented by the re-educated macrophages owing to the up-regulation of various antigen presenting mediators,resulting in infiltration and activation of cytotoxic T lymphocytes.As a result,the nanosystem triggers a robust antitumor immune response in combination with PD-L1 antibody to inhibit tumor growth and metastasis.This work provides a non-cytotoxic nanomedicine to modulate tumor immune microenvironment by reprograming macrophages.
基金supported by National Natural Science Foundation of China[No.21677066]Guangzhou Municipal Science and Technology Project[No.201803030027]。
文摘Objective Although benzene is a confirmed environmental carcinogen,the mechanism of its carcinogenicity remains largely unclear.The suggested oncogene,miR-221,is elevated and plays important roles in various tumors,but its role in benzene-induced carcinogenesis remains unknown.Methods In the present study,we constructed hydroquinone(HQ,a representative metabolite of benzene with biological activity)-transformed malignant cell line(16 HBE-t)and analyzed the level of miR-221 in it with qRT-PCR.Exosomes from 16 HBE-t cells incubated with or without an miR-221 inhibitor were isolated by ultracentrifugation,characterized by transmission electron microscopy and laser scanning confocal microscope,and then transfected into 16 HBE cells.The effects of exosomal miR-221 on apoptosis induced by HQ in recipient cells were determined using flow cytometry.Results The amount of miR-221 in 16 HBE-t was significantly increased compared with controls.When recipient cells ingested exosomes derived from 16 HBE-t,miR-221 was increased,and apoptosis induced by HQ was inhibited.Blocking miR-221 in 16 HBE-t using an inhibitor did not significantly alter miR-221 or apoptosis in recipient cells.Conclusion Exosomal miR-221 secreted by 16 HBE-t inhibits apoptosis induced by HQ in normal recipient cells.
基金This work was supported by the funds from the Medical and Health Science and Technology Development Project of Shandong Province,China(grant nos.2015WS0375 and 2019WS125)Scientific and Technological Project of Henan Province,China(grant nos.192102310114 and 192102310110).
文摘Objective:to explore the changes of the F-wave in the posterior tibial nerve of rabbits after different levels of lumbar spinal cord ischaemic injury and its correlation with motor function and the extent of lumbar spinal cord pathological damage.Methods:thirty New Zealand rabbits were randomly divided into 6 groups.The control group(n=5)was used to exclude the influence of anaesthesia and surgery on the F-wave.Different levels of lumbar arteries were ligated in the five experimental groups(n=5).The F-wave was recorded to observe the changes in the acute phase of spinal cord ischaemia.The correlation between the changes of the F-wave in the acute reversible phase and the motor function of the spinal cord was analysed.Motor functions were assessed after surgery and 2 d after vascular ligation.The specimens were taken 2 d after ligation for histopathologic observation.Results:the results for the control group indicated that anaesthesia and surgery did not affect the F-wave results.There was no statistically significant difference in the F-wave amplitudes and latency before and after ligation in the 1 and 2 level ligation groups.The F-wave changed immediately after ligation in the 3,4 and 5 ligation groups.The latency of the F-wave gradually extended,the amplitude of the F-wave gradually reduced.The amplitude variations of the F-wave were positively correlated with the motor function 2 d after ligation,there was a statistically significant difference.With the increase in the number of vascular ligation,the degree of destruction of the motor neurons in the anterior horn of the spinal cord in the pathological specimens increased.Conclusion:the F-waves in the posterior tibial nerve of rabbits were found to be sensitive to the lumbar spinal cord ischaemic injury and specific to predict motor function.
基金Key R&D Program of China(2021YFC2300101 YW)the National Natural Science Foundation of China(82172240 YW,82025001 JZ)+4 种基金Self-supporting Program of Guangzhou Laboratory(SRPG22-001,SRPG22-006)Guangdong Basic and Applied Research Projects(2023B1515020040 YW,2020A0505100063 JZ,2019B1515120068 JZ)ZhongNanShan Medical Foundation of Guangdong Province(ZNSA-2020001,ZNSA-2020013)State Key Laboratory of Respiratory Disease(SKLRD-Z-202214 YW,SKLRD-OP-202309 YW)Guangzhou Medical University(YP2022005 YW).
文摘Dear Editor,Recently,a number of new Omicron subvariants related to BA.4/5 and BA.2.75 have emerged and shown remarkable antibody evasion capacities,in particular BF.7,BQ.1,BQ.1.1,BA.2.75.2,XBB and XBB.1.5.1 Unsurprisingly,these new subvariants are quickly gaining prevalence worldwide.In fact,some of them have outcompeted BA.5 in the USA according to CDC’s national genomic surveillance data in which,as of 6th February 2023,XBB.1.5,BQ.1.1,BQ.1,XBB and BF.7 have achieved a dominance of 66.4%,19.9%,7.3%,2.3%and 0.5%in the USA,as compared to 0.5%for BA.5.In this report,using plasma samples collected from individuals following different vaccination strategies and COVID-19 convalescent donors,we performed pseudoviral neutralization assays to confirm severe reductions in neutralization titers against BF.7,BQ.1,BQ.1.1,BA.2.75.2,XBB and XBB.1.5 in comparison to other Omicron sub-lineages.XBB and XBB.1.5 were shown to be remarkably resistant to plasma neutralization in all tested cohorts.By comparing the differential neutralization profiles,we found that a heterologous booster with an aerosolized vaccine following 2 doses of inactivated vaccine seemed to be superior to other vaccination strategies.
基金Guangzhou Health Science and Technology Project(20201A011078)Guangzhou Science and Technology Project(202102010094)+5 种基金Guangdong Basic and Applied Basic Research Foundation(2021A1515012550)Clinical research project of Guangzhou Medical University Second Affiliated Hospital(2021-LCYJ-05)Guangdong Medical Research Fund(A2022255)Key Clinical Specialty of Guangzhou Medical University(0F03031)Guangzhou Laboratory(EKPG21-30-3)Guangzhou key discipline of urology.The funding sources had no role in the study design,data collection,analysis,interpretation,or writing of the report.
文摘Homologous booster,heterologous booster,and Omicron variants breakthrough infection(OBI)could improve the humoral immunity against Omicron variants.Questions concerning about memory B cells(MBCs)and T cells immunity against Omicron variants,features of long-term immunity,after booster and OBI,needs to be explored.Here,comparative analysis demonstrate antibody and T cell immunity against ancestral strain,Delta and Omicron variants in Omicron breakthrough infected patients(OBIPs)are comparable to that in Ad5-nCoV boosted healthy volunteers(HVs),higher than that in inactivated vaccine(InV)boosted HVs.However,memory B cells(MBCs)immunity against Omicron variants was highest in OBIPs,followed by Ad5-nCoV boosted and InV boosted HVs.OBIPs and Ad5-nCoV boosted HVs have higher classical MBCs and activated MBCs,and lower naïve MBCs and atypical MBCs relative to both vaccine boosted HVs.Collectively,these data indicate Omicron breakthrough infection elicit higher MBCs and T cells against SARS-CoV-2 especially Omicron variants relative to homologous InV booster and heterologous Ad5-nCoV booster.
基金supported by the State Key Program of National Natural Science of China(81230007)
文摘In heart disease, transforming growth factor-β1 (TGF-β1) converts fibroblasts into myofibroblasts, which synthesize and se- crete fibrillar type I and III collagens. The purpose of the present study was to investigate how hydrogen sulfide (HzS) sup- presses TGF-~l-induced differentiation of human cardiac fibroblasts to myofibroblasts. Human cardiac fibroblasts were se- rum-starved in fibroblast medium for 16 h before exposure to TGF-β1 (10 ng mL-1) for 24 h with or without sodium hydrosul- fide (NariS, 100 μmol L-1, 30 min pretreatment) treatment. NariS, an exogenous HzS donor, potently inhibited the prolifera- tion and migration of TGF-β1-induced human cardiac fibroblasts and regulated their cell cycle progression. Furthermore, NariS treatment led to suppression of fibroblast differentiation into myofibroblasts, and reduced the levels of collagen, TGF-β1, and activated Smad3 in TGF-β1-induced human cardiac fibroblasts in vitro. We therefore conclude that H2S sup- presses TGF-β1-stimulated conversion of fibroblasts to myofibroblasts by inhibiting the TGF-β1/Smad3 signaling pathway, as well as by inhibiting the proliferation, migration, and cell cycle progression of human cardiac myofibroblasts. These effects of H2S may play significant roles in cardiac remodeling associated with heart failure.
基金Open access funding provided by University of Eastern Finland(UEF)including Kuopio University Hospital.
文摘Background Neonatal hyperbilirubinemia is observed in most newborns,and 5–15%of neonates require phototherapy.Phototherapy is efective but often prolongs hospitalization and has both short-term and potential long-term harms.The aim of this systematic review and meta-analysis was to evaluate the role of ursodeoxycholic acid(UDCA)combined with phototherapy in neonatal hyperbilirubinemia.Methods A literature search was conducted on September 1,2021;590 studies were screened,and 17 full texts were assessed by two authors.We included randomized controlled trials with or without placebo intervention.Primary outcomes were changes in total bilirubin levels at 24 hours and phototherapy duration.We calculated mean diferences with 95%confdence intervals(CI).Results Six studies with 880 neonates were included.Of these studies,only two used a placebo-controlled double-blinded design.The overall risk of bias was high in one and moderate in four of the included studies.The mean decrease in the total bilirubin level during the frst 24 hours was 2.06 mg/dL(95%CI 0.82–3.30;six studies)greater in the UDCA treatment group.The phototherapy duration was 19.7 hours(95%CI 10.4–29.1;fve studies)shorter in the UDCA treatment group.Conclusions We found low-quality evidence that UDCA as an adjuvant to phototherapy seems to decrease total bilirubin faster and shorten phototherapy duration compared to standard treatment.Further studies are needed to confrm the efcacy,acute and long-term outcomes,and safety before implementing UDCA as an adjuvant to phototherapy in neonatal hyperbilirubinemia.
基金grants from the Projects of the Priority Academic Program Development of Jiangsu Higher Education InstitutionNantong Society Undertaking and Technological Innovation(HS2014078)+1 种基金National Natural Science Foundation(81200634 and 81370982)the International S.& T.Cooperation Program (2013DFA32150) of China
文摘Worldwide incidence of hepatocellular carcinoma (HCC) is steadily increasing,highlighting its status as a public health concern,particularly due to its significant association with other comorbidities,such as diabetes.However,nonalcoholic fatty liver disease (NAFLD) has emerged as a primary risk factor,with its own prevalence increasing in recent years,and it has gradually caught up with the historical primary etiological factors of infection with hepatitis B virus and hepatitis C virus,exposure to aflatoxin,or alcohol liver disease.The deeply worrisome aspects of all of these high risk factors,however,are their remarkable presence within populations.Systemic and genetic mechanisms involved in the malignant transformation of liver cells,as well as useful biomarkers of early stage HCC are being investigated.However,the exact mechanisms underlying the interrelation of NAFLD and HCC remain largely unknown.In this review,some of the recent advances in our understanding of liver lipid accumulation are summarized and discussed to provide insights into the relationship between NAFLD and hepatocyte malignant transformation.(C) 2016 The Second Affiliated Hospital of Chongqing Medical University.Published by XIA & HE Publishing Inc.All rights reserved.