ObjectiveTo investigate the influence of entecavir （ETV） versus tenofovir alafenamide fumarate （TAF） on renal function in previously untreated patients with chronic hepatitis B （CHB）. MethodsA retrospective analysis was performed for the clinical data of 167 previously untreated CHB patients who received ETV or TAF treatment for at least 48 weeks at the outpatient service of Department of Infectious Diseases in The First Affiliated Hospital of Nanchang University from September 2019 to November 2023， and according to the antiviral drug used， they were divided into ETV group with 117 patients and TAF group with 50 patients. In order to balance baseline clinical data， propensity score matching （PSM） was used for matching and analysis at a ratio of 2∶1， and the two groups were compared in terms of estimated glomerular filtration rate （eGFR） and the incidence rate of abnormal renal function at week 48. According to eGFR at week 48， the patients were divided into normal renal function group and abnormal renal function group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The multivariate Logistic regression analysis was used to investigate the influencing factors for abnormal renal function， and the receiver operating characteristic （ROC） curve was used to assess the performance of each indicator in predicting abnormal renal function. The Kaplan-Meier method was used to analyze the cumulative incidence rate of abnormal renal function， and the log-rank test was used for comparison. The analysis of variance with repeated measures was used to compare the dynamic changes of eGFR during antiviral therapy in CHB patients. ResultsAfter PSM matching， there were 100 patients in the ETV group and 50 patients in the TAF group. There were no significant differences in baseline clinical data between the ETV group and the TAF group （all P>0.05）， with an eGFR level of 112.29±9.92 mL/min/1.73 m² in the ETV group and 114.72±12.15 mL/min/1.73 m² in the TAF group. There was a reduction in eGFR from baseline to week 48 in both groups， and compared with the TAF group at week 48， the ETV group had a significantly lower eGFR （106.42±14.12 mL/min/1.73 m² vs 112.25±13.44 mL/min/1.73 m²， t=-2.422， P=0.017） and a significantly higher incidence rate of abnormal renal function （17.00% vs 4.00%， χ²=5.092， P=0.024）. After the patients were divided into normal renal function group with 131 patients and abnormal renal function group with 19 patients， the univariate analysis showed that there were significant differences between the two groups in age （Z=-2.039， P=0.041）， treatment drug （ETV/TAF） （χ²=5.092， P=0.024）， and baseline eGFR level （t=4.023， P<0.001）， and the multivariate Logistic regression analysis showed that baseline eGFR （odds ratio ［OR］=0.896， 95% confidence interval ［CI］： 0.841 — 0.955， P<0.001） and treatment drug （OR=5.589， 95%CI： 1.136 — 27.492， P=0.034） were independent influencing factors for abnormal renal function. Baseline eGFR had an area under the ROC curve of 0.781 in predicting abnormal renal function in CHB patients， with a cut-off value of 105.24 mL/min/1.73 m²， a sensitivity of 73.68%， and a specificity of 82.44%. The Kaplan-Meier curve analysis showed that the patients with baseline eGFR≤105.24 mL/min/1.73 m² had a significantly higher cumulative incidence rate of abnormal renal function than those with baseline eGFR>105.24 mL/min/1.73 m² （χ²=22.330， P<0.001）， and the ETV group had a significantly higher cumulative incidence rate of abnormal renal function than the TAF group （χ²=4.961， P=0.026）. With the initiation of antiviral therapy， both the ETV group and the TAF group had a significant reduction in eGFR （F=5.259， P<0.001）， but the ETV group only had a significant lower level of eGFR than the TAF group at week 48 （t=-2.422， P=0.017）； both the baseline eGFR≤105.24 mL/min/1.73 m² group and the baseline eGFR>105.24 mL/min/1.73 m² group had a significant reduction in eGFR （F=5.712， P<0.001）， and there was a significant difference in eGFR between the two groups at baseline and weeks 12， 24， 36， and 48 （t=-13.927， -9.780， -8.835， -9.489， and -8.953， all P<0.001）. ConclusionFor CHB patients initially treated with ETV or TAF， ETV antiviral therapy has a higher risk of renal injury than TAF therapy at week 48.

Diabetic neuropathy is a common chronic complication of diabetes and is characterized by high in-cidence and disability rates.It is the result of various metabolic imbalances,including disorders of glucose metabolism,lipid metabolism,and insulin signaling abnormalities caused by insulin deficiency or resistance.The pathogenesis of dia-betic neuropathy is closely related to lipid metabolism disorders.Disorders of lipid metabolism,especially abnormal changes in fatty acids,sphingolipids and cholesterol,are key causal factors and new therapeutic targets for diabetic neu-ropathy.This article reviews the disorder of lipid metabolism under diabetic conditions,and its role and mechanism in the occurrence and development of diabetic neuropathy,with the aim of providing new ideas for diabetic neuropathy treatment.

Objective To summarize the current situation of the implementation of the death case discussion system in county-level medical institutions and analyze the existing problems,to attempt to make suggestions for improvement.Methods Judgmental sampling method was used in this study.A self-made questionnaire was used to conduct field investigation on the im-plementation of the death case discussion system in 16 county-level medical institutions in Chongqing,and semi-structured inter-views were conducted with medical staff.Results All county-level medical institutions have established death case discussion system,but there are many differences in connotative quality.There are many problems in system implementation,such as unclear scope of death case discussion,formality,irregular discussion,poor quality of connotation and lack of systematic supervision.Conclusion As a core medical system,the death case discussion system is an important tool for medical quality management.The medical quality management and medical staff must place a high value on the significance of death case discussion.In order to enhance medical quality and ensure patient safety,we must adhere to the principles of openness and honesty,systematic criti-cism,non-recrimination and non-punishment to conduct death case discussion in time and standardize,keep a record of death case discussions and enhance supervision.

Humans ; Urinary Bladder Neoplasms/pathology* ; Carcinoma, Transitional Cell/pathology* ; Genetic Markers ; Biomarkers, Tumor/genetics* ; Urothelium/pathology*

Objective To investigate the effect of dynamic monitoring of occlusal force on the final therapeutic effect and the change of periodontal supporting tissue during combined periodontal orthodontic treatment.Methods The periodontal clinical index of 20 patients with traditional periodontal orthodontic treatment and 20 patients with combined periodontal orthodontic treatment assisted by T-Scan Ⅲ and Anycheck digital occlusion analysis system were compared before,during and after treatment,as well as the changes of bite force,bite time and tooth mobility in the experimental group.Results The depth of periodontal pocket(PD),loss of attachment(AL),bleeding index(BI)and tooth looseness were significantly reduced after combined periodontal orthodontic treatment in both groups.In the control group,the percentage of anterior and posterior biting force changed obviously,and the occlusion force balance was improved.Conclusion The combined treatment of periodontitis and orthodontics can improve the periodontal tissue of patients with periodontitis,and T-Scan system can observe and guide the adjustment of occlusal and better achieve occlusion force balance.

Objective To observe the value of habitat model based on lung CT for predicting brain metastasis(BM)of lung adenocarcinoma with epidermal growth factor receptor(EGFR)mutation.Methods Data of plain lung CT of 198 lung adenocarcinoma patients with EGFR-mutant were retrospectively analyzed.The patients were divided into training set(n=138)and test set(n=60)at the ratio of 7∶3,and further divided into BM subgroup and non-BM subgroup in each set.Then a logistic regression(LR)clinical model was constructed using variables being statistically different between subgroups in training set.For features extracted from tumor and subregion of tumor,radiomics models and habitat models were constructed based on random forest,Gaussian process(GP)and support vector machine(SVM)algorithms,and the best radiomics and habitat models with generalization ability were screened.LR combined model was constructed based on the predicted values of the best radiomics and habitat models with generalization ability,as well as the clinical model.Then receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each model for predicting BM of lung adenocarcinoma with EGFR-mutant.Spearman correlation analysis was performed to observe the correlations between Ki-67 and habitat features of lung adenocarcinoma with EGFR-mutant.Results AUC of LR clinical model,GP radiomics model,SVM habitat model and LR combined model for predicting BM of lung adenocarcinoma with EGFR-mutant was 0.700,0.726,0.801 and 0.834 in training set,0.754,0.600,0.715 and 0.848 in test set,respectively.AUC of LR combined model was higher than that of LR clinical model in training set(P＜0.001),also higher than that of GP radiomics model in test set(P=0.010).Compared with GP radiomics model and SVM habitat model,the performance of LR combined model was significantly and positively improved in training set(integrated discrimination improvement index[IDI]=8.60%,8.55%,both P＜0.001).Ki-67 level of EGFR-mutant lung adenocarcinoma was lowly and positively correlated with habitatmap_original_glszm_lalgle extracted from habitat map(│rs│=0.201,P=0.004).Conclusion The habitat model based on lung CT could be used to predict BM of lung adenocarcinoma with EGFR-mutant effectively.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 has emerged as a promising target for antibody-drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy in cancer treatment, their application in solid tumors is hindered by their high molecular weight, poor tumor penetration, and release of cytotoxic molecules. Therefore, a recombinant immunotoxin was developed based on a shark-derived variable domain of immunoglobulin new antigen receptor (VNAR) antibody. VNARs are only one-tenth the size of IgG antibodies and possess remarkable tissue penetration capabilities and high stability. In this study, a shark VNAR phage display library was created, leading to the identification of shark VNAR-5G8 that targets TROP-2. VNAR-5G8 exhibited a high affinity and cellular internalization ability towards cells expressing high levels of TROP-2. Epitope analysis revealed that VNAR-5G8 recognizes a hidden epitope consisting of CRD and TY-1 on TROP-2. Subsequently, VNAR-5G8 was fused with a truncated form of Pseudomonas exotoxin (PE38) to create the recombinant immunotoxin (5G8-PE38), which exhibited significant anti-tumor activity in vitro and in vivo. Overall, this study highlights the promise of 5G8-PE38 as a valuable candidate for cancer therapy.

BACKGROUND: Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient's medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu's Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion. METHODS: Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration <10 g/dL were randomly assigned to an individualized strategy, a restrictive strategy following China's guideline or a liberal strategy with a transfusion threshold of hemoglobin concentration <9.5 g/dL. We evaluated two primary outcomes: the proportion of patients who received red blood cells (superiority test) and a composite of in-hospital complications and all-cause mortality by day 30 (non-inferiority test). RESULTS: We enrolled 1182 patients: 379, 419, and 384 received individualized, restrictive, and liberal strategies, respectively. Approximately 30.6% (116/379) of patients in the individualized strategy received a red-cell transfusion, less than 62.5% (262/419) in the restrictive strategy (absolute risk difference, 31.92%; 97.5% confidence interval [CI]: 24.42-39.42%; odds ratio, 3.78%; 97.5% CI: 2.70-5.30%; P <0.001), and 89.8% (345/384) in the liberal strategy (absolute risk difference, 59.24%; 97.5% CI: 52.91-65.57%; odds ratio, 20.06; 97.5% CI: 12.74-31.57; P <0.001). No statistically significant differences were found in the composite of in-hospital complications and mortality by day 30 among the three strategies. CONCLUSION: The individualized red-cell transfusion strategy using the West-China-Liu's Score reduced red-cell transfusion without increasing in-hospital complications and mortality by day 30 when compared with restrictive and liberal strategies in elective non-cardiac surgeries. TRIAL REGISTRATION ClinicalTrials.gov, NCT01597232.
Humans ; Adult ; Postoperative Complications ; Erythrocyte Transfusion/adverse effects* ; Blood Transfusion ; Hospitals ; Hemoglobins/analysis*

Objective:To investigate the expression of long non-coding RNA (lncRNA) MTATP6P1 in melanoma and its effect on the proliferation, migration and invasion of melanoma cells by targeting miRNA-411-5p (miR-411-5p).Methods:A total of 461 samples of melanoma tissues and paracancerous tissues (>2 cm from the tumor margin) were collected from the tumor-associated lncRNA database (TANRIC database updated in July 2021), and the expression of MTATP6P1 was compared between the two groups. The bioinformatics software lncRNA Disease v2.0 was used to predict the possible binding site microRNA (miRNA) of MTATP6P1. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression level of MTATP6P1 in melanoma cells A-375, WM266-4, VMM5A, A2058 and normal human epidermal melanocytes PIG1; and the lowest relative expression level of cells in MTATP6P1 were divided into MTATP6P1 group (transfected with MTATP6P1 overexpression plasmid) and NC group (transfected with blank plasmid). The proliferation ability of A-375 cells was detected by using CCK-8 method; the migration ability of A-375 cells was detected by using scratch test; the invasion ability of A-375 cells was detected by using Transwell assay; the targeting relationship between MTATP6P1 and miR-411-5p was detected by using dual luciferase reporter gene assay; Western blot was used to detect the expression of ERK signaling pathway related proteins in cells.Results:The relative expression levels of MTATP6P1 in melanoma tissues and adjacent tissues were 9.82±0.58 and 11.56±0.16, respectively. The expression level of MTATP6P1 in melanoma tissues was lower than that in paracancerous tissues ( t = 9.56, P = 0.009). The relative expression levels of MTATP6P1 in normal human epidermal melanocyte PIG1 and melanoma cells A-375, WM266-4, VMM5A, and A2058 were 1.01±0.13, 0.12±0.02, 0.66±0.04, 0.39±0.07, 0.49±0.05; the relative expression level of MTATP6P1 in melanoma cells was lower than that in PIG1 cells (all P < 0.05), and then A-375 cells with the lowest relative expression level were taken to perform the subsequent experiments. The relative expression levels of MTATP6P1 in A-375 cells of MTATP6P1 group and NC group were 14.83±1.67 and 1.02±0.30, respectively ( t = 8.13, P < 0.001). After 16, 24, 32, and 40 h of culture, the proliferation ability of the cells in the MTATP6P1 group was lower than that in NC group (all P < 0.05). The scratch healing rates of A-375 cells in MTATP6P1 group and NC group were (26±7)% and (55±4)%, respectively; the scratch healing rate in MTATP6P1 group was lower than that in NC group ( t = 3.48, P = 0.009). The invasive number of A-375 cells in MTATP6P1 group and NC group were (32±12) and (116±17), respectively; the number of invasive cells in MTATP6P1 group was lower than that in NC group ( t = 4.11, P = 0.006). The results of dual luciferase reporter gene assay showed that there was a targeting relationship between MTATP6P1 and miR-411-5p. The relative expression level of miR-411-5p in A-375 cells of MTATP6P1 group and NC group was 1.04±0.16 and 5.37±0.68, respectively; the expression level of miR-411-5p in MTATP6P1 group was lower than that in NC group ( t = 6.20, P < 0.001). The expressions of ERK signaling pathway proteins p-Ras, p-Raf, p-MEK1, p-RSK, and AP-1 in A-375 cells of MTATP6P1 group were lower than those in NC group. Conclusions:MTATP6P1 inhibits the proliferation, migration and invasion of melanoma A-375 cells through targeting miR-411-5p.