BACKGROUND Many studies have demonstrated the benefit of complete multivessel revascularization versus culprit-only intervention in patients of ST-segment elevation myocardial infarction(STEMI)and multivessel coronary...BACKGROUND Many studies have demonstrated the benefit of complete multivessel revascularization versus culprit-only intervention in patients of ST-segment elevation myocardial infarction(STEMI)and multivessel coronary artery disease.However,only a few single-center retrospective studies were performed on small Chinese cohorts.Our study aims to demonstrate the advantage of multivessel percutaneous intervention(PCI)strategy on 30-day in-hospital outcomes to patients with STEMI and multivessel disease in larger Chinese population.METHODS From the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome(CCC-ACS)project,5935 patients with STEMI and multivessel disease undergoing PCI and hospitalized for fewer than 30 days were analyzed.After 5:1 propensity score matching,3577 patients with culprit-only PCI and 877 with in-hospital multivessel PCI were included.The primary outcome was major adverse cardiovascular and cerebrovascular event(MACCE),defined as a composite of myocardial infarction,all-cause death,stent thrombosis,heart failure,and stroke.RESULTS Multivariable logistic regression analysis revealed that in-hospital multivessel PCI was associated with lower risk of 30-day MACCE(adjusted OR=0.75,95%CI:0.57-0.98,P=0.032)than culprit-only PCI and conferred no increased risk of allcause death,myocardial infarction,stent thrombosis,stroke,or bleeding.Subgroup analysis showed that MACCE reduction was observed more often from patients with trans-femoral access(OR=0.34,95%CI:0.15-0.74)than with trans-radial access(OR=0.87,95%CI:0.66-1.16,P for interaction=0.017).CONCLUSIONS The in-hospital multivessel PCI strategy was associated with a lower risk of 30-day MACCE than culprit-only PCI in patients with STEMI and multivessel coronary artery disease.展开更多
Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running o...Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and metabolites.It showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia genera.Metabolic profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis signaling.In conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose intolerance.We further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.展开更多
Glanzmann’s thrombasthenia(GT)is an inherited autosomal recessive bleeding disorder,resulting from mutations in the ITGA2B and ITGB3 genes,that lead to a defect in the platelet membrane integrinαIIbβ3.[1]As integri...Glanzmann’s thrombasthenia(GT)is an inherited autosomal recessive bleeding disorder,resulting from mutations in the ITGA2B and ITGB3 genes,that lead to a defect in the platelet membrane integrinαIIbβ3.[1]As integrinαIIbβ3 plays an important role in thrombus formation,the clinical manifestation of GT includes bleeding(mostly mucocutaneous)and purpura.For this reason,patients with GT are typically thought to be unlikely to suffer from thromboembolic incidents.Antithrombin is an anticoagulant that inhibits thrombin and is activated factor X and other serine proteases in the coagulation cascade.[2]Antithrombin deficiency is an autosomal dominant hereditary disease with an approximate prevalence of 1/500 in the overall population.[3]In contrast to the hemorrhagic tendency of GT,patients with antithrombin deficiency are at increased risk of thromboembolism,especially in the venous system.Herein,we describe a rare case of GT and antithrombin deficiency coexisting in a single patient.Rivaroxaban was used for the treatment of pulmonary embolism(PE)and deep vein thrombosis(DVT).展开更多
BACKGROUND While most complications of cervical surgery are reversible,some,such as symptomatic postoperative spinal epidural hematoma(SEH),which generally occurs within 24 h,are associated with increased morbidity an...BACKGROUND While most complications of cervical surgery are reversible,some,such as symptomatic postoperative spinal epidural hematoma(SEH),which generally occurs within 24 h,are associated with increased morbidity and mortality.Delayed neurological dysfunction is diagnosed in cases when symptoms present>3 d postoperatively.Owing to its rarity,the risk factors for delayed neurological dysfunction are unclear.Consequently,this condition can result in irreversible neurological deficits and serious consequences.In this paper,we present a case of postoperative SEH that developed three days after hematoma evacuation.CASE SUMMARY A 68-year-old man with an American Spinal Injury Association(ASIA)grade C injury was admitted to our hospital with neck pain and tetraplegia following a fall.The C3-C7 posterior laminectomy and the lateral mass screw fixation surgery were performed on the tenth day.Postoperatively,the patient showed no changes in muscle strength or ASIA grade.The patient experienced neck pain and subcutaneous swelling on the third day postoperatively,his muscle strength decreased,and his ASIA score was grade A.Magnetic resonance imaging showed hypointense signals on T1 weighted image(T1WI)and T2WI located behind the epidural space,with spinal cord compression.Emergency surgical intervention for the hematoma was performed 12 h after onset.Although hypoproteinemia and pleural effusion did not improve in the perioperative period,the patient recovered to ASIA grade C on day 30 after surgery,and was transferred to a functional rehabilitation exercise unit.CONCLUSION This case shows that amelioration of low blood albumin and pleural effusion is an important aspect of the perioperative management of cervical surgery.Surgery to relieve the pressure on the spinal cord should be performed as soon as possible to decrease neurological disabilities.展开更多
To the editor:Major depressive disorder(MDD)is a heterogeneous disorder with varying symptom presentations and underlying biological mechanisms.1 The mainstream neurobiological hypotheses of depression involve monoami...To the editor:Major depressive disorder(MDD)is a heterogeneous disorder with varying symptom presentations and underlying biological mechanisms.1 The mainstream neurobiological hypotheses of depression involve monoamine neurotransmitters,hypothalamic-pituitary-adrenal axis,immune-inflammation and the glutamate system.展开更多
BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To e...BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.展开更多
Objective To investigate the current enteral feeding practices in hospitalized late preterm infants in the Beijing area of China. Methods A multi-center, cross-sectional study was conducted. Infants born after 34 week...Objective To investigate the current enteral feeding practices in hospitalized late preterm infants in the Beijing area of China. Methods A multi-center, cross-sectional study was conducted. Infants born after 34 weeks and before 37 weeks of gestation were enrolled from 25 hospitals in the Beijing area of China from October 2015 to October 2017. Data on enteral feeding practices were collected and analyzed. Results A total of 1,463 late preterm infants were enrolled, with a mean gestational age(GA) of 35.6(34.9, 36.1) weeks. The percentage of exclusive breastfeeding was 4.5% at the initiation of enteral feeding but increased to 14.4% at discharge. When human milk was not available, most infants(46.1%) were fed with preterm infant formula. The rate of exclusive human milk feeding in infants born at 34 weeks gestation was higher than at discharge(21.1% of infants born at 34 weeks' GA versus 12.1% of infants born at 35 weeks' GA versus 12.3% of infants born at 36 weeks' GA, P 〈 0.001). Only 28.4% of late preterm infants achieved full enteral feeding at discharge, and only 19.2% achieved 120 kcal/(kg·d) by enteral feeding at discharge. Importantly, 40.5% of infants did not regain the birth weight at discharge. Conclusion Enteral feeding support of late preterm infants has not been standardized to achieve optimal growth. Moreover, the human milk feeding rate was low, and many late preterm infants did not achieve the goal of enteral feeding and failed to regain birth weight at the time of discharge. More aggressive enteral feedings protocols are needed to promote human milk feeding and optimize growth for late preterm infants.展开更多
Objective This study aimed to evaluate the epidemiological,clinical and mycological characteristics of invasive candidiasis(IC)in China.Methods A ten-year retrospective study including 183 IC episodes was conducted in...Objective This study aimed to evaluate the epidemiological,clinical and mycological characteristics of invasive candidiasis(IC)in China.Methods A ten-year retrospective study including 183 IC episodes was conducted in a tertiary hospital in Beijing,China.Results The overall incidence of IC from 2010–2019 was 0.261 episodes per 1,000 discharges.Candidemia(71.0%)was the major infective pattern;70.3%of the patients tested positive for Candida spp.colonization before IC and the median time to develop an invasive infection after colonization was13.5 days(interquartile range:4.5–37.0 days).Candida albicans(45.8%)was the most prevalent species,followed by Candida parapsilosis(19.5%),Candida glabrata(14.2%)and Candida tropicalis(13.7%).C.non-albicans IC was more common in patients with severe anemia(P=0.018),long-term hospitalization(P=0.015),hematologic malignancies(P=0.002),continuous administration of broad-spectrum antibiotics(P<0.001)and mechanical ventilation(P=0.012).In vitro resistance testing showed that11.0%of the Candida isolates were resistant/non-wild type(non-WT)to fluconazole,followed by voriconazole(9.6%),micafungin(3.8%),and caspofungin(2.9%).Fluconazole was the most commonly used drug to initiate antifungal therapy both before and after the proven diagnosis(52.6%and 54.6%,respectively).The 30-day and 90-day all-cause mortality rates were 24.5%and 32.7%,respectively.Conclusion The incidence of IC has declined in the recent five years.C.non-albicans contributed to more than half of the IC cases.Fluconazole can be used as first-line therapy if resistant strains are not prevalent.Prospective,multi-center surveillance of the clinical and mycological characteristics of IC is required.展开更多
BACKGROUND Catheter ablation for atrial fibrillation(AF)is commonly performed worldwide.However,the clinical charac-teristics of hospitalized patients with AF and national trends in catheter ablation at tertiary hospi...BACKGROUND Catheter ablation for atrial fibrillation(AF)is commonly performed worldwide.However,the clinical charac-teristics of hospitalized patients with AF and national trends in catheter ablation at tertiary hospitals in China remain unreported.METHODS This study used the Chinese national database(Hospital Quality Monitoring System)from 2013 to 2016,which is a mandatory database that collects the front page of patients’medical records for hospital accreditation,to describe the clinical cha-racteristics of patients with AF as an overall cohort and as subgroups divided by catheter ablation and sex.RESULTS Of 597,919 AF patients first admitted,57,983 patients underwent catheter ablation[56,384 cases(97.2%)of radiofre-quency ablation and 1599 cases(2.8%)of cryoablation]at 746 tertiary hospitals.Nearly 10%of patients hospitalized with AF at ter-tiary hospitals in China underwent catheter ablation,and the percentage of patients undergoing catheter ablation was on the rise bet-ween 2013 and 2016,and the number of cases increased by 2.5 times.Compared with AF patients who did not undergo catheter ablation,those who did were younger,more frequently male,and had fewer baseline comorbidities.Although the overall CHA_(2)DS_(2)-VASc score revealed over half of the patients were high-risk,patients who underwent catheter ablation were mostly low-risk(71.2%of males and 59.1%of females).Considering in-hospital adverse events,the overall pericardial tamponade and all-cause death incidences were 0.2%(0.6%in the ablation group)and 1.2%(0.1%in the ablation group),respectively;both of which were higher in females than males.CONCLUSIONS In this study,AF patients who underwent catheter ablation were relatively young,had a low thrombosis risk,and had few comorbidities and adverse events.Females were older and experienced more complications than males.展开更多
We isolated a novel strain of Alphaproteobacteria from a patient,who had medical history of chronic rhinitis for more than twenty years and recently experienced local skin abscess and ulcer. He eventually died of mult...We isolated a novel strain of Alphaproteobacteria from a patient,who had medical history of chronic rhinitis for more than twenty years and recently experienced local skin abscess and ulcer. He eventually died of multiple organ failure due to multi-antibiotics resistance.We identified the microorganism by 16SrRNA sequencing and found that it belonged to the genus Rhodoplanes. It was named as Rhodoplanes sp.strain ZLJ-0.It is resumed that Rhodoplanes sp.strain ZLJ-0 might be an emerging human pathogen involving in unknown febrile conditions and could cause local infection of any tissues or organs.Differential diagnosis of febrile patients should be conducted in clinical practice and research on emerging pathogens of Alphaproteobacteria should be performed to determine the epidemiology,clinical symptoms and pathogenic features of these pathogens.展开更多
A controlled intervention study was to promote rational antibiotic prophylaxis in clean surgeries in Chinese tertiary hospitals from 2008 to 2009. The effect of the intervention was measured and compared before and af...A controlled intervention study was to promote rational antibiotic prophylaxis in clean surgeries in Chinese tertiary hospitals from 2008 to 2009. The effect of the intervention was measured and compared before and after intervention (intervention group, IG, including twelve hospitals), and compared with the control group (CG, including 164 tertiary hospitals distributed in 31 provinces). There were a total of 3961 and 657 cases identified in IG & CG for the study. Comparing the changes of IG with CG following the 3rd intervention, the proportion of antibiotics use without indication decreased from 61.9% (IG) & 84.4% (CG) (χ2 test, P χ2 test, P > 0.05);the rationality scores increased from 55.4 (IG) & 57.6 (CG) (t test, P > 0.05) to 77.0 (IG) & 64.3 (CG) (t test,展开更多
BACKGROUND The preoperative prediction of peritoneal metastasis(PM)in gastric cancer would prevent unnecessary surgery and promptly indicate an appropriate treatment plan.AIM To explore the predictive value of viscera...BACKGROUND The preoperative prediction of peritoneal metastasis(PM)in gastric cancer would prevent unnecessary surgery and promptly indicate an appropriate treatment plan.AIM To explore the predictive value of visceral fat(VF)parameters obtained from preoperative computed tomography(CT)images for occult PM and to develop an individualized model for predicting occult PM in patients with gastric carcinoma(GC).METHODS A total of 128 confirmed GC cases(84 male and 44 female patients)that underwent CT scans were analyzed and categorized into PM-positive(n=43)and PM-negative(n=85)groups.The clinical characteristics and VF parameters of two regions of interest(ROIs)were collected.Univariate and stratified analyses based on VF volume were performed to screen for predictive characteristics for occult PM.Prediction models with and without VF parameters were established by multivariable logistic regression analysis.RESULTS The mean attenuations of VF_(ROI 1)and VF_(ROI 2)varied significantly between the PM-positive and PMnegative groups(P=0.044 and 0.001,respectively).The areas under the receiver operating characteristic curves(AUCs)of VF_(ROI 1)and VF_(ROI 2)were 0.599 and 0.657,respectively.The mean attenuation of VF_(ROI 2)was included in the final prediction combined model,but not an independent risk factor of PM(P=0.068).No significant difference was observed between the models with and without mean attenuation of VF(AUC:0.749 vs 0.730,P=0.339).CONCLUSION The mean attenuation of VF is a potential auxiliary parameter for predicting occult PM in patients with GC.展开更多
Recurrent oral ulcer is a painful oral mucosal disorder that affects 20%of the world’s population.The lack of a radical cure due to its unknown underlying cause calls for innovative symptomatic treatments.This work r...Recurrent oral ulcer is a painful oral mucosal disorder that affects 20%of the world’s population.The lack of a radical cure due to its unknown underlying cause calls for innovative symptomatic treatments.This work reports a hyaluronic acid-based dissolvablemicroneedle patch(ROUMNpatch,short for recurrent oral ulcer microneedle)loaded with dexamethasone acetate,vitamin C and tetracaine hydrochloride for the treatment of recurrent oral ulcers.The ROUMN patch shows enhancement in both the anti-inflammatory effect elicited by dexamethasone and the pro-proliferation effect of vitamin C.In vitro experiments show that ROUMN has a higher efficiency in suppressing lipopolysaccharide(LPS)-induced interleukin-6(IL-6)expression than dexamethasone alone.Cell proliferation and migrationwere also significantly promoted byROUMNcompared to vitamin C alone.The healing-promoting effect of ROUMN was also verified in vivo using an acetic acid-cauterized oral ulcer model in rats.ROUMN as a treatment accelerated the healing process of oral ulcers,shortening the total healing time to 5 days compared with the 7 days required by treatment using watermelon frost,a commonly used over-the-counter(OTC)drug for oral ulcers.The rapid dissolution of the hyaluronic acid-based microneedles and the superior healing-promoting effect of the drug combination could lead to a broad application prospect of the ROUMN patch in the treatment of recurrent oral ulcers.展开更多
Objective: The aim of this study was to investigate the factors influencing pathological complete response(pCR)rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab(H) + pertuzumab(P)] th...Objective: The aim of this study was to investigate the factors influencing pathological complete response(pCR)rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab(H) + pertuzumab(P)] therapy combined with chemotherapy. Additionally, the consistency of the Miller-Payne and residual cancer burden(RCB)systems in evaluating the efficacy of neoadjuvant therapy for early human epidermal growth factor receptor-2(HER2)+ breast cancer was analyzed.Methods: The clinicopathological data of female patients with early-stage HER2+ breast cancer who received dual-target neoadjuvant therapy at 26 hospitals of the Chinese Society of Breast Surgery(CSBrS) from March 2019 to December 2021 were collected. Patients were allocated to four groups: the HER2 immunohistochemistry(IHC)3+/hormone receptor(HR)-, IHC3+/HR+, IHC2+ in situ hybridization(ISH)+/HR-and IHC2+ ISH+/HR+groups. The overall pCR rate for patients, the pCR rate in each group and the factors affecting the pCR rate were analyzed. The consistency between the Miller-Payne and RCB systems in assessing the efficacy of neoadjuvant therapy was analyzed.Results: From March 1, 2019, to December 31, 2021, 77,376 female patients with early-stage breast cancer were treated at 26 hospitals;18,853(24.4%) of these patients were HER2+. After exclusion of unqualified patients, 2,395 patients who received neoadjuvant dual-target(H+P) therapy combined with chemotherapy were included in this study. The overall pCR rate was 53.0%, and the patients' HR statuses and different HER2+ statuses were significantly correlated with the pCR rate(P<0.05). The consistency of the pathological efficacy assessed by the Miller-Payne and RCB systems was 88.0%(κ=0.717, P<0.001).Conclusions: Different HER2 expression statuses and HR expression statuses are correlated with the pCR rate after dual-target neoadjuvant therapy in HER2+ breast cancer patients. There is a relatively good consistency between Miller-Payne and RCB systems in evaluating the pathologic efficacy of neoadjuvant therapy for HER2+breast cancer.展开更多
Objective:Liver cancer is a deadly malignancy associated with high mortality and morbidity.Less than 20%of patients with advanced liver cancer respond to a single anti-PD-1 treatment.The high heterogeneity of neutroph...Objective:Liver cancer is a deadly malignancy associated with high mortality and morbidity.Less than 20%of patients with advanced liver cancer respond to a single anti-PD-1 treatment.The high heterogeneity of neutrophils in the tumor immune microenvironment in liver cancer may contribute to resistance to immune checkpoint blockade(ICB).However,the underlying mechanism remains largely unknown.Methods:We established an orthotopic liver cancer model by using transposable elements to integrate the oncogenes Myc and KrasG12Dinto the genome in liver cells from conditional Trp53 null/null mice(pTMK/Trp53^(-/-)).Flow cytometry and immunohistochemistry were used to assess the changes in immune cells in the tumor microenvironment.An ex vivo coculture assay was performed to test the inhibitory effects of tumor-associated neutrophils(TANs)on CD8^(+)T cells.The roles of neutrophils,T cells,and NK cells were validated through antibody-mediated depletion.The efficacy of the combination of neutrophil depletion and ICB was evaluated.Results:Orthotropic pTMK/Trp53^(-/-)mouse liver tumors displayed a moderate response to anti-Ly6G treatment but not PD-1 blockade.Depletion of neutrophils increased the infiltration of CD8^(+)T cells and decreased the number of exhausted T cells in the tumor microenvironment.Furthermore,depletion of either CD8^(+)T or NK cells abrogated the antitumor efficacy of anti-Ly6G treatment.Moreover,the combination of anti-Ly6G with anti-PD-L1 enhanced the infiltration of cytotoxic CD8^(+)T cells and thereafter resulted in a significantly greater decrease in tumor burden.Conclusions:Our data suggest that TANs may contribute to the resistance of liver cancer to ICB,and combining TAN depletion with T cell immunotherapy synergistically increases antitumor efficacy.展开更多
Objective: Cancer immunotherapy has made remarkable advances in recent years, but its effectiveness in treating gastric cancer is often limited by the complexity of the tumor microenvironment and the lack of effective...Objective: Cancer immunotherapy has made remarkable advances in recent years, but its effectiveness in treating gastric cancer is often limited by the complexity of the tumor microenvironment and the lack of effective biomarkers. This study aimed to identify effective biomarkers for immunotherapy treatment by characterizing the tumor microenvironment.Methods: We retrieved the RNA-seq data from gastric cancer patients treated with the programmed death 1(PD-1) blockade pembrolizumab. Differentially expressed genes associated with clinical outcomes were identified and further analyzed using gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Gene signature scores were calculated by single sample Gene Set Enrichment Analysis(ssGSEA). The infiltration levels of immune cells were quantified using the xCell website. Cell type enrichment analysis was performed to compare treatment response and non-response groups, and regression analysis was used to investigate the relationship between interferon gamma(IFNγ) immune response and immune cell infiltration. Biomarkers were identified using least absolute shrinkage and selection operator(LASSO) analysis.Results: Compared to normal tissues, cytokine activity and interleukin-6 production were highly activated in gastric tumors. Responders to pembrolizumab showed significantly up-regulated expression of IFNγ responserelated genes. Cell type enrichment analysis revealed that Th1 cells were significantly enriched in the tumor microenvironment of responders. Regression analysis indicated that Th1 cells induced IFNγ response more efficiently than other cell types. Using signatures of Th1 cells, stromal cells and IFNγ response, a set of eight genes were identified that effectively predicted the efficacy of immunotherapy treatment and patient prognosis.Conclusions: Th1 cells promote therapeutic efficacy of PD-1 blockade by promoting IFNγ immune response in gastric cancer. The identified biomarkers have the potential to improve the effectiveness of immunotherapy treatment for gastric cancer patients.展开更多
BACKGROUND Video-assisted thoracic surgery(VATS)lobectomy is a common treatment for patients with early-stage lung cancer.Some patients can experience slight gastrointestinal discomfort after lobectomy for a moment.Ga...BACKGROUND Video-assisted thoracic surgery(VATS)lobectomy is a common treatment for patients with early-stage lung cancer.Some patients can experience slight gastrointestinal discomfort after lobectomy for a moment.Gastroparesis is a gastrointestinal disorder that can be severe;it is associated with an increased risk of aspiration pneumonia and impaired postoperative recovery.Here,we report a rare case of gastroparesis after VATS lobectomy.CASE SUMMARY A 61-year-old man underwent VATS right lower lobectomy uneventfully but had an obstruction of the upper digestive tract 2 d after surgery.Acute gastroparesis was diagnosed after emergency computed tomography and oral iohexol X-ray imaging.After gastrointestinal decompression and administration of prokinetic drugs,the patient’s gastrointestinal symptoms improved.Since perioperative medication was applied according to the recommended dose and there was no evidence of electrolyte imbalance,intraoperative periesophageal vagal nerve injury was the most likely underlying cause of gastroparesis.CONCLUSION Although gastroparesis is a rare perioperative complication following VATS,clinicians should be on the alert when patients complain about gastrointestinal discomfort.When surgeons resect paraesophageal lymph nodes with electrocautery,excessive ambient heat and compression of paraesophageal hematoma might induce vagal nerve dysfunction.展开更多
BACKGROUND Neonatal hyperinsulinism can result from perinatal stress,genetic disorders,or syndromes,which can lead to persistent or intractable hypoglycemia in newborns.Mutations in the ABCC8 gene result in abnormal f...BACKGROUND Neonatal hyperinsulinism can result from perinatal stress,genetic disorders,or syndromes,which can lead to persistent or intractable hypoglycemia in newborns.Mutations in the ABCC8 gene result in abnormal functioning of potassium channel proteins in pancreaticβ-cells,leading to an overproduction of insulin and congenital hyperinsulinemia.CASE SUMMARY We report a case of a high-birth-weight infant with postnatal hypoglycemia and hyperinsulinemia,whose mother had pregestational diabetes mellitus with poor glycemic control and whose sister had a similar history at birth.Whole-exome sequencing revealed a new mutation in the ABCC8 gene in exon 8(c.1257T>G),which also occurred in his sister and mother;thus,the patient was diagnosed with neonatal hyperinsulinism with an ABCC8 mutation.With oral diazoxide treatment,the child’s blood glucose returned to normal,and the pediatrician gradually discontinued treatment because of the child’s good growth and development.CONCLUSION We report a new mutation locus in the ABCC8 gene.This mutation locus warrants attention for genetic disorders and long-term prognoses of hypoglycemic children.展开更多
本研究目的是探讨血清N-聚糖模型在285例丙氨酸转移酶(alanine aminotransferase,ALT)水平正常(<40 U·L^(-1))的慢性乙型肝炎(慢性乙肝)患者中诊断显著肝纤维化和肝硬化的临床意义。入组患者均进行肝组织活检,并使用Ishak评分...本研究目的是探讨血清N-聚糖模型在285例丙氨酸转移酶(alanine aminotransferase,ALT)水平正常(<40 U·L^(-1))的慢性乙型肝炎(慢性乙肝)患者中诊断显著肝纤维化和肝硬化的临床意义。入组患者均进行肝组织活检,并使用Ishak评分系统评估患者肝组织纤维化程度。应用基于DNA测序仪的荧光糖电泳技术检测患者血清N-聚糖图谱,每例患者的血清样本中共鉴定出9个N-聚糖峰。利用机器学习算法,即随机森林(random forest,RF)构建更理想的血清N-聚糖模型,以诊断显著肝纤维化(≥F3)和肝硬化(≥F5),并比较血清N-聚糖模型和其他纤维化标志物的诊断效能。肝组织活检结果显示,有显著肝纤维化和肝硬化患者分别占63.86%(182/285)和16.49%(47/285),有显著炎症患者为4.91%(14/285)。血清N-聚糖RF-A模型具有很好的诊断显著肝纤维化(≥F3)的效能,其受试者工作特征曲线下面积(area under receiver operating characteristic curve,AUROC)为0.94,与肝活检的符合率为90.45%。在诊断肝硬化(≥F5)时,血清N-聚糖RF-B模型的AUROC为0.97,与肝组织活检的符合率为88.94%。血清N-聚糖模型(RF-A和RF-B)的诊断效能优于肝硬度值测量(liver stiffness measurement,LSM)、基于4因子的纤维化指数(fibrosis index based on the four factors,FIB-4)和天冬氨酸转氨酶与血小板比率指数(aspartate aminotransferase-to-platelet ratio index,APRI)。在ALT水平正常的慢性乙肝患者中,血清N-聚糖模型可作为诊断显著肝纤维化或肝硬化的潜在生物标志物。展开更多
Objective To assess the feasibility of internal suspension technique in retroperitoneal robot-assisted laparoscopic partial nephrectomy(rRAPN)with a new robotic platform called KangDuo Surgical Robot-01(KD-SR-01)syste...Objective To assess the feasibility of internal suspension technique in retroperitoneal robot-assisted laparoscopic partial nephrectomy(rRAPN)with a new robotic platform called KangDuo Surgical Robot-01(KD-SR-01)system(Suzhou KangDuo Robot Co.,Ltd.,Suzhou,China)and discuss its surgical technique.Methods A 44-year-old male patient was admitted with a 2.5 cm tumor on dorsolateral upper pole of the left kidney.The R.E.N.A.L.nephrometry score of this patient was 4x.This patient underwent rRAPN with KD-SR-01.The perinephric fat between the tumor and Gerota's fascia was preserved,which was used for internal suspension traction during tumor resection.Postoperative follow-up data were collected.Results The surgery was successfully carried out with a duration of 127 min,in which the docking time was 6 min 25 s and console time was 60 min.The warm ischemia time was 19 min 53 s,and the estimated blood loss was 0 mL.The pathological histology showed a pathological tumor stage 1a clear cell renal cell carcinoma,with a negative surgical margin.The World Health Organization/International Society of Urological Pathology(WHO/ISUP)grade of this patient was Grade 2.No recurrence was observed during the 6-month follow-up.Conclusion Internal suspension in rRAPN is feasible and effective with use of the new robotic system KD-SR-01.展开更多
基金We thank all hospitals and staff participating in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome(CCC-ACS)project.The CCC-ACS Project is a collaborative project of the American Heart Association and the Chinese Society of Cardiology.The American Heart Association received funding from Pfizer through an independent grant for learning and change and AstraZeneca as a quality improvement initiative.
文摘BACKGROUND Many studies have demonstrated the benefit of complete multivessel revascularization versus culprit-only intervention in patients of ST-segment elevation myocardial infarction(STEMI)and multivessel coronary artery disease.However,only a few single-center retrospective studies were performed on small Chinese cohorts.Our study aims to demonstrate the advantage of multivessel percutaneous intervention(PCI)strategy on 30-day in-hospital outcomes to patients with STEMI and multivessel disease in larger Chinese population.METHODS From the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome(CCC-ACS)project,5935 patients with STEMI and multivessel disease undergoing PCI and hospitalized for fewer than 30 days were analyzed.After 5:1 propensity score matching,3577 patients with culprit-only PCI and 877 with in-hospital multivessel PCI were included.The primary outcome was major adverse cardiovascular and cerebrovascular event(MACCE),defined as a composite of myocardial infarction,all-cause death,stent thrombosis,heart failure,and stroke.RESULTS Multivariable logistic regression analysis revealed that in-hospital multivessel PCI was associated with lower risk of 30-day MACCE(adjusted OR=0.75,95%CI:0.57-0.98,P=0.032)than culprit-only PCI and conferred no increased risk of allcause death,myocardial infarction,stent thrombosis,stroke,or bleeding.Subgroup analysis showed that MACCE reduction was observed more often from patients with trans-femoral access(OR=0.34,95%CI:0.15-0.74)than with trans-radial access(OR=0.87,95%CI:0.66-1.16,P for interaction=0.017).CONCLUSIONS The in-hospital multivessel PCI strategy was associated with a lower risk of 30-day MACCE than culprit-only PCI in patients with STEMI and multivessel coronary artery disease.
基金sponsored by National Natural Science Foundation of China (81800703 and 81970701)Beijing Nova Program (Z201100006820117 and 20220484181)+7 种基金Beijing Municipal Natural Science Foundation (7184252 and 7214258)the Fundamental Research Funds for the Central Universitiesthe Fundamental Research Funds for the Central Universities (BMU2021MX013)Peking University Clinical Scientist Training Program (BMU2023PYJH022)China Endocrine and Metabolism Young Scientific Talent Research Project (2022-N-02-01)Peking University Medicine Seed Fund for Interdisciplinary ResearchChina Diabetes Young Scientific Talent Research ProjectBethune-Merck Diabetes Research Fund of Bethune Charitable Foundation (G2018030)。
文摘Exercise training is critical for the early prevention and treatment of obesity and diabetes mellitus.However,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and metabolites.It showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia genera.Metabolic profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis signaling.In conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose intolerance.We further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.
文摘Glanzmann’s thrombasthenia(GT)is an inherited autosomal recessive bleeding disorder,resulting from mutations in the ITGA2B and ITGB3 genes,that lead to a defect in the platelet membrane integrinαIIbβ3.[1]As integrinαIIbβ3 plays an important role in thrombus formation,the clinical manifestation of GT includes bleeding(mostly mucocutaneous)and purpura.For this reason,patients with GT are typically thought to be unlikely to suffer from thromboembolic incidents.Antithrombin is an anticoagulant that inhibits thrombin and is activated factor X and other serine proteases in the coagulation cascade.[2]Antithrombin deficiency is an autosomal dominant hereditary disease with an approximate prevalence of 1/500 in the overall population.[3]In contrast to the hemorrhagic tendency of GT,patients with antithrombin deficiency are at increased risk of thromboembolism,especially in the venous system.Herein,we describe a rare case of GT and antithrombin deficiency coexisting in a single patient.Rivaroxaban was used for the treatment of pulmonary embolism(PE)and deep vein thrombosis(DVT).
文摘BACKGROUND While most complications of cervical surgery are reversible,some,such as symptomatic postoperative spinal epidural hematoma(SEH),which generally occurs within 24 h,are associated with increased morbidity and mortality.Delayed neurological dysfunction is diagnosed in cases when symptoms present>3 d postoperatively.Owing to its rarity,the risk factors for delayed neurological dysfunction are unclear.Consequently,this condition can result in irreversible neurological deficits and serious consequences.In this paper,we present a case of postoperative SEH that developed three days after hematoma evacuation.CASE SUMMARY A 68-year-old man with an American Spinal Injury Association(ASIA)grade C injury was admitted to our hospital with neck pain and tetraplegia following a fall.The C3-C7 posterior laminectomy and the lateral mass screw fixation surgery were performed on the tenth day.Postoperatively,the patient showed no changes in muscle strength or ASIA grade.The patient experienced neck pain and subcutaneous swelling on the third day postoperatively,his muscle strength decreased,and his ASIA score was grade A.Magnetic resonance imaging showed hypointense signals on T1 weighted image(T1WI)and T2WI located behind the epidural space,with spinal cord compression.Emergency surgical intervention for the hematoma was performed 12 h after onset.Although hypoproteinemia and pleural effusion did not improve in the perioperative period,the patient recovered to ASIA grade C on day 30 after surgery,and was transferred to a functional rehabilitation exercise unit.CONCLUSION This case shows that amelioration of low blood albumin and pleural effusion is an important aspect of the perioperative management of cervical surgery.Surgery to relieve the pressure on the spinal cord should be performed as soon as possible to decrease neurological disabilities.
文摘To the editor:Major depressive disorder(MDD)is a heterogeneous disorder with varying symptom presentations and underlying biological mechanisms.1 The mainstream neurobiological hypotheses of depression involve monoamine neurotransmitters,hypothalamic-pituitary-adrenal axis,immune-inflammation and the glutamate system.
基金Supported by the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation,No.GZC20231088President Foundation of The Third Affiliated Hospital of Southern Medical University,China,No.YP202210.
文摘BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.
基金supported by Science and Technology Project of Beijing Health and Family Planning Commission[2016001]the CAMS Initiative for Innovative Medicine[2016-12M-1-008]
文摘Objective To investigate the current enteral feeding practices in hospitalized late preterm infants in the Beijing area of China. Methods A multi-center, cross-sectional study was conducted. Infants born after 34 weeks and before 37 weeks of gestation were enrolled from 25 hospitals in the Beijing area of China from October 2015 to October 2017. Data on enteral feeding practices were collected and analyzed. Results A total of 1,463 late preterm infants were enrolled, with a mean gestational age(GA) of 35.6(34.9, 36.1) weeks. The percentage of exclusive breastfeeding was 4.5% at the initiation of enteral feeding but increased to 14.4% at discharge. When human milk was not available, most infants(46.1%) were fed with preterm infant formula. The rate of exclusive human milk feeding in infants born at 34 weeks gestation was higher than at discharge(21.1% of infants born at 34 weeks' GA versus 12.1% of infants born at 35 weeks' GA versus 12.3% of infants born at 36 weeks' GA, P 〈 0.001). Only 28.4% of late preterm infants achieved full enteral feeding at discharge, and only 19.2% achieved 120 kcal/(kg·d) by enteral feeding at discharge. Importantly, 40.5% of infants did not regain the birth weight at discharge. Conclusion Enteral feeding support of late preterm infants has not been standardized to achieve optimal growth. Moreover, the human milk feeding rate was low, and many late preterm infants did not achieve the goal of enteral feeding and failed to regain birth weight at the time of discharge. More aggressive enteral feedings protocols are needed to promote human milk feeding and optimize growth for late preterm infants.
基金the Major Infectious Diseases Such as AIDS and Viral Hepatitis Prevention and Control Technology Major Projects[2018ZX10712001-011]。
文摘Objective This study aimed to evaluate the epidemiological,clinical and mycological characteristics of invasive candidiasis(IC)in China.Methods A ten-year retrospective study including 183 IC episodes was conducted in a tertiary hospital in Beijing,China.Results The overall incidence of IC from 2010–2019 was 0.261 episodes per 1,000 discharges.Candidemia(71.0%)was the major infective pattern;70.3%of the patients tested positive for Candida spp.colonization before IC and the median time to develop an invasive infection after colonization was13.5 days(interquartile range:4.5–37.0 days).Candida albicans(45.8%)was the most prevalent species,followed by Candida parapsilosis(19.5%),Candida glabrata(14.2%)and Candida tropicalis(13.7%).C.non-albicans IC was more common in patients with severe anemia(P=0.018),long-term hospitalization(P=0.015),hematologic malignancies(P=0.002),continuous administration of broad-spectrum antibiotics(P<0.001)and mechanical ventilation(P=0.012).In vitro resistance testing showed that11.0%of the Candida isolates were resistant/non-wild type(non-WT)to fluconazole,followed by voriconazole(9.6%),micafungin(3.8%),and caspofungin(2.9%).Fluconazole was the most commonly used drug to initiate antifungal therapy both before and after the proven diagnosis(52.6%and 54.6%,respectively).The 30-day and 90-day all-cause mortality rates were 24.5%and 32.7%,respectively.Conclusion The incidence of IC has declined in the recent five years.C.non-albicans contributed to more than half of the IC cases.Fluconazole can be used as first-line therapy if resistant strains are not prevalent.Prospective,multi-center surveillance of the clinical and mycological characteristics of IC is required.
基金supported by the China-WHO Biennial Collaborative Projects 2016–2017(No.2016/648722–0).
文摘BACKGROUND Catheter ablation for atrial fibrillation(AF)is commonly performed worldwide.However,the clinical charac-teristics of hospitalized patients with AF and national trends in catheter ablation at tertiary hospitals in China remain unreported.METHODS This study used the Chinese national database(Hospital Quality Monitoring System)from 2013 to 2016,which is a mandatory database that collects the front page of patients’medical records for hospital accreditation,to describe the clinical cha-racteristics of patients with AF as an overall cohort and as subgroups divided by catheter ablation and sex.RESULTS Of 597,919 AF patients first admitted,57,983 patients underwent catheter ablation[56,384 cases(97.2%)of radiofre-quency ablation and 1599 cases(2.8%)of cryoablation]at 746 tertiary hospitals.Nearly 10%of patients hospitalized with AF at ter-tiary hospitals in China underwent catheter ablation,and the percentage of patients undergoing catheter ablation was on the rise bet-ween 2013 and 2016,and the number of cases increased by 2.5 times.Compared with AF patients who did not undergo catheter ablation,those who did were younger,more frequently male,and had fewer baseline comorbidities.Although the overall CHA_(2)DS_(2)-VASc score revealed over half of the patients were high-risk,patients who underwent catheter ablation were mostly low-risk(71.2%of males and 59.1%of females).Considering in-hospital adverse events,the overall pericardial tamponade and all-cause death incidences were 0.2%(0.6%in the ablation group)and 1.2%(0.1%in the ablation group),respectively;both of which were higher in females than males.CONCLUSIONS In this study,AF patients who underwent catheter ablation were relatively young,had a low thrombosis risk,and had few comorbidities and adverse events.Females were older and experienced more complications than males.
基金funded by the National Natural Science Foundation of China(No.30771854)National Basic Research Program of China(973 Program) 2010CB530200 (2010CB530206)
文摘We isolated a novel strain of Alphaproteobacteria from a patient,who had medical history of chronic rhinitis for more than twenty years and recently experienced local skin abscess and ulcer. He eventually died of multiple organ failure due to multi-antibiotics resistance.We identified the microorganism by 16SrRNA sequencing and found that it belonged to the genus Rhodoplanes. It was named as Rhodoplanes sp.strain ZLJ-0.It is resumed that Rhodoplanes sp.strain ZLJ-0 might be an emerging human pathogen involving in unknown febrile conditions and could cause local infection of any tissues or organs.Differential diagnosis of febrile patients should be conducted in clinical practice and research on emerging pathogens of Alphaproteobacteria should be performed to determine the epidemiology,clinical symptoms and pathogenic features of these pathogens.
文摘A controlled intervention study was to promote rational antibiotic prophylaxis in clean surgeries in Chinese tertiary hospitals from 2008 to 2009. The effect of the intervention was measured and compared before and after intervention (intervention group, IG, including twelve hospitals), and compared with the control group (CG, including 164 tertiary hospitals distributed in 31 provinces). There were a total of 3961 and 657 cases identified in IG & CG for the study. Comparing the changes of IG with CG following the 3rd intervention, the proportion of antibiotics use without indication decreased from 61.9% (IG) & 84.4% (CG) (χ2 test, P χ2 test, P > 0.05);the rationality scores increased from 55.4 (IG) & 57.6 (CG) (t test, P > 0.05) to 77.0 (IG) & 64.3 (CG) (t test,
基金Supported by Henan Province 2023 Scientific Research Projects Focused on Higher Education Project,China,No.23A320059.
文摘BACKGROUND The preoperative prediction of peritoneal metastasis(PM)in gastric cancer would prevent unnecessary surgery and promptly indicate an appropriate treatment plan.AIM To explore the predictive value of visceral fat(VF)parameters obtained from preoperative computed tomography(CT)images for occult PM and to develop an individualized model for predicting occult PM in patients with gastric carcinoma(GC).METHODS A total of 128 confirmed GC cases(84 male and 44 female patients)that underwent CT scans were analyzed and categorized into PM-positive(n=43)and PM-negative(n=85)groups.The clinical characteristics and VF parameters of two regions of interest(ROIs)were collected.Univariate and stratified analyses based on VF volume were performed to screen for predictive characteristics for occult PM.Prediction models with and without VF parameters were established by multivariable logistic regression analysis.RESULTS The mean attenuations of VF_(ROI 1)and VF_(ROI 2)varied significantly between the PM-positive and PMnegative groups(P=0.044 and 0.001,respectively).The areas under the receiver operating characteristic curves(AUCs)of VF_(ROI 1)and VF_(ROI 2)were 0.599 and 0.657,respectively.The mean attenuation of VF_(ROI 2)was included in the final prediction combined model,but not an independent risk factor of PM(P=0.068).No significant difference was observed between the models with and without mean attenuation of VF(AUC:0.749 vs 0.730,P=0.339).CONCLUSION The mean attenuation of VF is a potential auxiliary parameter for predicting occult PM in patients with GC.
基金the National Natural Science Foundation of China(Nos.62003023,32071407,52073138,52003018 and 52003019)Beijing Natural Science Foundation(No.7212204)Beijing Advanced Innovation Center for Biomedical Engineering and Beihang University.
文摘Recurrent oral ulcer is a painful oral mucosal disorder that affects 20%of the world’s population.The lack of a radical cure due to its unknown underlying cause calls for innovative symptomatic treatments.This work reports a hyaluronic acid-based dissolvablemicroneedle patch(ROUMNpatch,short for recurrent oral ulcer microneedle)loaded with dexamethasone acetate,vitamin C and tetracaine hydrochloride for the treatment of recurrent oral ulcers.The ROUMN patch shows enhancement in both the anti-inflammatory effect elicited by dexamethasone and the pro-proliferation effect of vitamin C.In vitro experiments show that ROUMN has a higher efficiency in suppressing lipopolysaccharide(LPS)-induced interleukin-6(IL-6)expression than dexamethasone alone.Cell proliferation and migrationwere also significantly promoted byROUMNcompared to vitamin C alone.The healing-promoting effect of ROUMN was also verified in vivo using an acetic acid-cauterized oral ulcer model in rats.ROUMN as a treatment accelerated the healing process of oral ulcers,shortening the total healing time to 5 days compared with the 7 days required by treatment using watermelon frost,a commonly used over-the-counter(OTC)drug for oral ulcers.The rapid dissolution of the hyaluronic acid-based microneedles and the superior healing-promoting effect of the drug combination could lead to a broad application prospect of the ROUMN patch in the treatment of recurrent oral ulcers.
基金supported by Beijing Science and Technology Innovation Medical Development Foundation (No. KC2021-JF-0167-01 and No. KC2021-JF-0167-24)。
文摘Objective: The aim of this study was to investigate the factors influencing pathological complete response(pCR)rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab(H) + pertuzumab(P)] therapy combined with chemotherapy. Additionally, the consistency of the Miller-Payne and residual cancer burden(RCB)systems in evaluating the efficacy of neoadjuvant therapy for early human epidermal growth factor receptor-2(HER2)+ breast cancer was analyzed.Methods: The clinicopathological data of female patients with early-stage HER2+ breast cancer who received dual-target neoadjuvant therapy at 26 hospitals of the Chinese Society of Breast Surgery(CSBrS) from March 2019 to December 2021 were collected. Patients were allocated to four groups: the HER2 immunohistochemistry(IHC)3+/hormone receptor(HR)-, IHC3+/HR+, IHC2+ in situ hybridization(ISH)+/HR-and IHC2+ ISH+/HR+groups. The overall pCR rate for patients, the pCR rate in each group and the factors affecting the pCR rate were analyzed. The consistency between the Miller-Payne and RCB systems in assessing the efficacy of neoadjuvant therapy was analyzed.Results: From March 1, 2019, to December 31, 2021, 77,376 female patients with early-stage breast cancer were treated at 26 hospitals;18,853(24.4%) of these patients were HER2+. After exclusion of unqualified patients, 2,395 patients who received neoadjuvant dual-target(H+P) therapy combined with chemotherapy were included in this study. The overall pCR rate was 53.0%, and the patients' HR statuses and different HER2+ statuses were significantly correlated with the pCR rate(P<0.05). The consistency of the pathological efficacy assessed by the Miller-Payne and RCB systems was 88.0%(κ=0.717, P<0.001).Conclusions: Different HER2 expression statuses and HR expression statuses are correlated with the pCR rate after dual-target neoadjuvant therapy in HER2+ breast cancer patients. There is a relatively good consistency between Miller-Payne and RCB systems in evaluating the pathologic efficacy of neoadjuvant therapy for HER2+breast cancer.
基金jointly supported by the National Natural Science Foundation of China(Grant Nos.81972735,82030079,and 81972656)Beijing Natural Science Foundation(Grant No.7212108)+2 种基金Michigan Medicine and PKU-HSC JI(Grant No.BMU2020JI005)Baidu Foundation(Grant No.2020BD015)Ying Shi Foundation。
文摘Objective:Liver cancer is a deadly malignancy associated with high mortality and morbidity.Less than 20%of patients with advanced liver cancer respond to a single anti-PD-1 treatment.The high heterogeneity of neutrophils in the tumor immune microenvironment in liver cancer may contribute to resistance to immune checkpoint blockade(ICB).However,the underlying mechanism remains largely unknown.Methods:We established an orthotopic liver cancer model by using transposable elements to integrate the oncogenes Myc and KrasG12Dinto the genome in liver cells from conditional Trp53 null/null mice(pTMK/Trp53^(-/-)).Flow cytometry and immunohistochemistry were used to assess the changes in immune cells in the tumor microenvironment.An ex vivo coculture assay was performed to test the inhibitory effects of tumor-associated neutrophils(TANs)on CD8^(+)T cells.The roles of neutrophils,T cells,and NK cells were validated through antibody-mediated depletion.The efficacy of the combination of neutrophil depletion and ICB was evaluated.Results:Orthotropic pTMK/Trp53^(-/-)mouse liver tumors displayed a moderate response to anti-Ly6G treatment but not PD-1 blockade.Depletion of neutrophils increased the infiltration of CD8^(+)T cells and decreased the number of exhausted T cells in the tumor microenvironment.Furthermore,depletion of either CD8^(+)T or NK cells abrogated the antitumor efficacy of anti-Ly6G treatment.Moreover,the combination of anti-Ly6G with anti-PD-L1 enhanced the infiltration of cytotoxic CD8^(+)T cells and thereafter resulted in a significantly greater decrease in tumor burden.Conclusions:Our data suggest that TANs may contribute to the resistance of liver cancer to ICB,and combining TAN depletion with T cell immunotherapy synergistically increases antitumor efficacy.
基金financially supported by the National Natural Science Foundation of China (No. 82030079, 82341005, 81972656 and 82173035)the National Science and Technology Major Project of China (No. 2022YFC3400 901)Sino-Russian Math Center in PKU。
文摘Objective: Cancer immunotherapy has made remarkable advances in recent years, but its effectiveness in treating gastric cancer is often limited by the complexity of the tumor microenvironment and the lack of effective biomarkers. This study aimed to identify effective biomarkers for immunotherapy treatment by characterizing the tumor microenvironment.Methods: We retrieved the RNA-seq data from gastric cancer patients treated with the programmed death 1(PD-1) blockade pembrolizumab. Differentially expressed genes associated with clinical outcomes were identified and further analyzed using gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Gene signature scores were calculated by single sample Gene Set Enrichment Analysis(ssGSEA). The infiltration levels of immune cells were quantified using the xCell website. Cell type enrichment analysis was performed to compare treatment response and non-response groups, and regression analysis was used to investigate the relationship between interferon gamma(IFNγ) immune response and immune cell infiltration. Biomarkers were identified using least absolute shrinkage and selection operator(LASSO) analysis.Results: Compared to normal tissues, cytokine activity and interleukin-6 production were highly activated in gastric tumors. Responders to pembrolizumab showed significantly up-regulated expression of IFNγ responserelated genes. Cell type enrichment analysis revealed that Th1 cells were significantly enriched in the tumor microenvironment of responders. Regression analysis indicated that Th1 cells induced IFNγ response more efficiently than other cell types. Using signatures of Th1 cells, stromal cells and IFNγ response, a set of eight genes were identified that effectively predicted the efficacy of immunotherapy treatment and patient prognosis.Conclusions: Th1 cells promote therapeutic efficacy of PD-1 blockade by promoting IFNγ immune response in gastric cancer. The identified biomarkers have the potential to improve the effectiveness of immunotherapy treatment for gastric cancer patients.
文摘BACKGROUND Video-assisted thoracic surgery(VATS)lobectomy is a common treatment for patients with early-stage lung cancer.Some patients can experience slight gastrointestinal discomfort after lobectomy for a moment.Gastroparesis is a gastrointestinal disorder that can be severe;it is associated with an increased risk of aspiration pneumonia and impaired postoperative recovery.Here,we report a rare case of gastroparesis after VATS lobectomy.CASE SUMMARY A 61-year-old man underwent VATS right lower lobectomy uneventfully but had an obstruction of the upper digestive tract 2 d after surgery.Acute gastroparesis was diagnosed after emergency computed tomography and oral iohexol X-ray imaging.After gastrointestinal decompression and administration of prokinetic drugs,the patient’s gastrointestinal symptoms improved.Since perioperative medication was applied according to the recommended dose and there was no evidence of electrolyte imbalance,intraoperative periesophageal vagal nerve injury was the most likely underlying cause of gastroparesis.CONCLUSION Although gastroparesis is a rare perioperative complication following VATS,clinicians should be on the alert when patients complain about gastrointestinal discomfort.When surgeons resect paraesophageal lymph nodes with electrocautery,excessive ambient heat and compression of paraesophageal hematoma might induce vagal nerve dysfunction.
文摘BACKGROUND Neonatal hyperinsulinism can result from perinatal stress,genetic disorders,or syndromes,which can lead to persistent or intractable hypoglycemia in newborns.Mutations in the ABCC8 gene result in abnormal functioning of potassium channel proteins in pancreaticβ-cells,leading to an overproduction of insulin and congenital hyperinsulinemia.CASE SUMMARY We report a case of a high-birth-weight infant with postnatal hypoglycemia and hyperinsulinemia,whose mother had pregestational diabetes mellitus with poor glycemic control and whose sister had a similar history at birth.Whole-exome sequencing revealed a new mutation in the ABCC8 gene in exon 8(c.1257T>G),which also occurred in his sister and mother;thus,the patient was diagnosed with neonatal hyperinsulinism with an ABCC8 mutation.With oral diazoxide treatment,the child’s blood glucose returned to normal,and the pediatrician gradually discontinued treatment because of the child’s good growth and development.CONCLUSION We report a new mutation locus in the ABCC8 gene.This mutation locus warrants attention for genetic disorders and long-term prognoses of hypoglycemic children.
基金supported by the Major Science and Technology Special Project of China Thirteenth Five-year Plan(2018ZX10732401-003-015)the National Science and Technology Major Project(2013ZX10002005 and 2017ZX10203202)。
文摘本研究目的是探讨血清N-聚糖模型在285例丙氨酸转移酶(alanine aminotransferase,ALT)水平正常(<40 U·L^(-1))的慢性乙型肝炎(慢性乙肝)患者中诊断显著肝纤维化和肝硬化的临床意义。入组患者均进行肝组织活检,并使用Ishak评分系统评估患者肝组织纤维化程度。应用基于DNA测序仪的荧光糖电泳技术检测患者血清N-聚糖图谱,每例患者的血清样本中共鉴定出9个N-聚糖峰。利用机器学习算法,即随机森林(random forest,RF)构建更理想的血清N-聚糖模型,以诊断显著肝纤维化(≥F3)和肝硬化(≥F5),并比较血清N-聚糖模型和其他纤维化标志物的诊断效能。肝组织活检结果显示,有显著肝纤维化和肝硬化患者分别占63.86%(182/285)和16.49%(47/285),有显著炎症患者为4.91%(14/285)。血清N-聚糖RF-A模型具有很好的诊断显著肝纤维化(≥F3)的效能,其受试者工作特征曲线下面积(area under receiver operating characteristic curve,AUROC)为0.94,与肝活检的符合率为90.45%。在诊断肝硬化(≥F5)时,血清N-聚糖RF-B模型的AUROC为0.97,与肝组织活检的符合率为88.94%。血清N-聚糖模型(RF-A和RF-B)的诊断效能优于肝硬度值测量(liver stiffness measurement,LSM)、基于4因子的纤维化指数(fibrosis index based on the four factors,FIB-4)和天冬氨酸转氨酶与血小板比率指数(aspartate aminotransferase-to-platelet ratio index,APRI)。在ALT水平正常的慢性乙肝患者中,血清N-聚糖模型可作为诊断显著肝纤维化或肝硬化的潜在生物标志物。
文摘Objective To assess the feasibility of internal suspension technique in retroperitoneal robot-assisted laparoscopic partial nephrectomy(rRAPN)with a new robotic platform called KangDuo Surgical Robot-01(KD-SR-01)system(Suzhou KangDuo Robot Co.,Ltd.,Suzhou,China)and discuss its surgical technique.Methods A 44-year-old male patient was admitted with a 2.5 cm tumor on dorsolateral upper pole of the left kidney.The R.E.N.A.L.nephrometry score of this patient was 4x.This patient underwent rRAPN with KD-SR-01.The perinephric fat between the tumor and Gerota's fascia was preserved,which was used for internal suspension traction during tumor resection.Postoperative follow-up data were collected.Results The surgery was successfully carried out with a duration of 127 min,in which the docking time was 6 min 25 s and console time was 60 min.The warm ischemia time was 19 min 53 s,and the estimated blood loss was 0 mL.The pathological histology showed a pathological tumor stage 1a clear cell renal cell carcinoma,with a negative surgical margin.The World Health Organization/International Society of Urological Pathology(WHO/ISUP)grade of this patient was Grade 2.No recurrence was observed during the 6-month follow-up.Conclusion Internal suspension in rRAPN is feasible and effective with use of the new robotic system KD-SR-01.