BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Ferroptosis is a novel type of oxidatively regulated cell death driven by iron-dependent lipid peroxidation.As the main site of iron utilization and oxidative metabolism,mitochondria are the main source of intracellular reactive oxy-gen species.Ferroptosis is associated with the severe impairment of mitochondrial structure and function,bioenergetics,and metabolism.Alzheimer disease(AD)is a devastating progressive neurodegenerative disease with the main clinical manifestation of decline in memory and cognitive function.Emerging evidence suggests that mitochondrial dysfunction plays a significant role in the process of ferroptosis in AD.This article elaborates on the mechanism of ferroptosis,mito-chondrial dysfunction and its role in ferroptosis in AD,and the treatment of AD,in order to provide a new perspective for exploring new strategies for the prevention and treatment of AD.

BACKGROUND:The mechanisms and targets of alendronate in the treatment of osteoporosis still need to be investigated in depth. OBJECTIVE:To investigate the mechanism by which alendronate regulates bone metabolism in rats with osteoporosis and to perform a bioinformatics analysis of differentially expressed proteins. METHODS:Female Sprague-Dawley rats were randomly divided into three groups(n=12 per group):model group,alendronate group and sham-operated group.Animal models of osteoporosis were prepared using ovariectomy in the model and alendronate groups.At 4 weeks after modeling,rats in the alendronate group were gavaged with alendronate;the other two groups were given the equal volume of normal saline.After 12 weeks of continuous gavage,the bone mineral density of the tibia was measured and the lumbar spine of the rats was taken for proteomic analysis using Tandem mass tag-liquid chromatography-tandem mass spectrometry technique to identify differentially expressed proteins for gene ontology,Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction analysis. RESULTS AND CONCLUSION:There were 32 up-regulated proteins and 51 down-regulated proteins identified between the alendronate group and model group.Gene ontology enrichment analysis showed that the differentially expressed proteins were mainly involved in molecular functions,such as binding and catalytic activity,and in biological processes,such as cellular process and metabolic process.Kyoto Encylopedia of Genes and Genomes enrichment analysis showed that the differentially expressed proteins in the alendronate group and model group were mainly involved in the biosynthesis of pantothenate and coenzyme A.Protein-protein interaction analysis indicated that among the differentially expressed proteins in the alendronate group and model group,Hspa1l,Enpp3,Unc45a,Myh9 and Cant1 were located at the nodes of the protein-protein interaction network and were closely related to bone metabolism.Overall,these findings indicate that alendronate may regulate bone metabolism in the rat model of osteoporosis by regulating the expression of differentially expressed proteins and biosynthesis of pantothenate and coenzyme A.

Gastrointestinal angiodysplasia(GIA)or gastrointestinal vascular malformation(GIVM)is a disease that affects the entire digestive tract with lesions which are insidious,multiple,and easy to regenerate.The lesions usually lead to repeated latent gastrointestinal bleeding,especially in elderly patients.The main clinical features of this disorder are chronic gastrointestinal bleeding and refractory anemia.Previously,there was a lack of recognized effective and safe methods and drug interventions for the treatment of GIA.In recent years,observational studies and case reports have suggested that somatostatin analogues may be effective in the treatment of GIA bleeding,but there is a lack of double-blind randomized controlled study support.Traditional invasive treatment methods,such as angiographic embolization,endoscopic local therapy,and surgical resection,have limited therapeutic use in GIA.Recently,multicenter,double-blind,randomized controlled trials have confirmed that thalidomide has certain efficacy in reducing the incidence of rebleeding and the requirements for blood transfusion in GIA.This paper aimed to summarize the progress in the treatment of GIA and provide reference for clinicians.

Objective To retrospectively analyze the periprocedural and postprocedural antithrombotic therapy regimens for patients undergoing percutaneous left atrial appendage closure(PLAAC)at Nanjing Drum Tower Hospital(hereinafter referred to as"the hospital")and their association with prognosis,and to provide a basis for antithrombotic therapy in clinical practice for such patients.Methods We systematically collected medical records of non-valvular atrial fibrillation patients underwent PLAAC treatment from January 2018 to January 2022 at our hospital.We recorded basic patient information,preoperative left atrial appendage(LAA)thrombus screening,and antithrombotic regimens,and analyzed the incidence of bleeding and thrombotic events during the periprocedural period and up to 12 months postprocedure.Results A total of 96 patients underwent PLAAC,with 86 included in the final analysis.Eight patients had LAA thrombus detected by transesophageal echocardiography before the procedure,and all thrombi resolved after one month of extended antithrombotic therapy.There was one bleeding event in the continuous anticoagulation group during the periprocedural period,while no bleeding events occurred in the interrupted anticoagulation group.Within one year postprocedure,11 patients(18.0%)in the continuous anticoagulation group and 4 patients(16.0%)in the interrupted anticoagulation group experienced bleeding events.All patients adhered to anticoagulant therapy as prescribed for the first three months postprocedure;between three to six months postprocedure,33.7%of patients received dual antiplatelet therapy(DAPT),and 29.1%discontinued therapy;between six to twelve months,47.7%of patients received single antiplatelet therapy(SAPT)and 48.8%discontinued therapy.During the one-year follow-up,there was one case each of device-related thrombus,ischemic stroke,and cerebral hemorrhage,indicating a low overall incidence of adverse events.Conclusion In the real-world setting,the individualized antithrombotic regimens provided by physicians at the hospital,both periprocedurally and postprocedurally,were reasonable and consistent with guidelines.However,poor medication adherence was a significant issue among patients.It is recommended that clinical pharmacists actively engage in pharmacotherapy monitoring and enhance medication education to improve medication adherence.

BACKGROUND: Among malignant tumors, lung cancer has the highest mortality rate. Small cell lung cancer (SCLC) is a kind of malignant lung cancer. Its doubling time is very fast. Patients are prone to drug resistance during treatment, and their condition often deteriorates rapidly after recurrence. Except for topotecan, there is a lack of effective second-line single-agent chemotherapy. This study aims to analysis the efficacy and safety of irinotecan (CPT-11) in the second-line treatment of refractory and relapsed SCLC. METHODS: A total of 107 SCLC patients were collected from the Department of Oncology, Jilin Guowen Hospital, who were diagnosed from April 2012 to March 2020, relapsed within 6 months after first-line treatment, and received second-line chemotherapy with single-agent CPT-11. Follow-up until November 2020, calculate the patient's progression free survival (PFS) and overall survival (OS), and summarize the effects and adverse reactions of CPT-11 chemotherapy. RESULTS: The patient's median PFS was 3.8 (3.4-4.4) months, median OS was 8.1 (6.5-10.9) months, objective response rate (ORR) was 16.82% (18/107), and DCR was 55.14% (59/107). The incidence of grade 3-4 adverse reactions in patients was relatively low. Among them, neutropenia was 13.08%, delayed diarrhea was 7.48%, nausea and vomiting was 17.76%, and liver function impairment was 6.54%. The influencing factors of PFS in single-agent CPT-11 second-line chemotherapy were gender (P=0.001), NSE (P=0.029), and effusion (P=0.040). While the influencing factors of OS were NSE level only (P=0.033). CONCLUSIONS For patients with refractory relapsed SCLC, CPT-11 single-agent second-line chemotherapy has a certain effect, is well tolerated, and is worthy of promotion.
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Objective:To identify the clinical phenotypes, diagnosis, and treatment of five children with DiGeorge syndrome finally diagnosed by gene, with review of the literature.Methods:The clinical data of five children with DiGeorge syndrome admitted to our hospital were collected and sorted out. Copy number variation sequencing (CNV-seq) based on next generation sequencing (NGS) technology was used to diagnose the genetic etiology of the children. The relationship between phenotypes and genotype among these five children were emphatically compared.Results:The five children collected in this study were all younger than 6 months. The course of the disease was more than 2 months to 1 year. Most of the first symptoms were convulsions and/or repeated infection. All of them had different degrees of growth retardation, with or without special facial features, epilepsy, congenital heart disease, etc. The similar blood ionized calcium levels revealed hypocalcemia, but the frequency and severity of convulsions were different. The copy number variation of chromosome 22q11.21 was detected in all these five children, and the deletion fragment was between 2.56-2.6 Mb, which was mostly coincident with the classical deletion region of DiGeorge syndrome (chr22: 19009792-21452445) recorded in Decipher database. One case was suggested to be a novel mutation, and the rest were of unknown origin.Conclusions:DiGeorge syndrome has great clinical heterogeneity. CNV-seq based on NGS technology is not only conducive to accurate genetic etiological diagnosis, but also helpful for understanding the corresponding relationship between clinical phenotype and genotype of hereditary syndrome, improving clinicians′ understanding and avoiding misdiagnosis.

Objective: To understand the status of awarences and the influencing factors of food safety among medical students in Shangdong Province,and to provide a reference for improving a healthy eating habit among students on their knowledge about food safety,attitude and behavior. Methods: A total of 2 322 students from 2 medical colleges and universities in Shandong province selected through stratified cluster sampling were investigated with questionnaires. Results: Univariate analysis of variance showed that food safety knowledge differed by gender, grade, major, origin of student, whether learned nutrition knowledge, monthly cost on food (χ2/H=20.48, 128.02, 98.61, 36.50, 77.60, 171.03,P<0.01). In multiple Logistic regression analysis, results showed that gender, major,origin of student, monthly cost on food and the attention of food affect college students’ food safety awareness (P<0.05). Conclusion Food safety awareness among medical students in Shandong Province is relatively high but varies by multiple factors. It is necessary to improve food safety awareness of medical students through various channels.