This study aimed to explore the mechanisms and molecular targets of total flavones of Abelmoschus manihot(TFA) plus empagliflozin(EM) in attenuating diabetic tubulopathy(DT) by targeting mitochondrial homeostasis and pyroptosis-apoptosis-necroptosis(PANoptosis). In the in vivo study, the authors established the DT rat models through a combination of uninephrectomy, administration of streptozotocin via intraperitoneal injections, and exposure to a high-fat diet. Following modeling successfully, the DT rat models received either TFA, EM, TFA+EM, or saline(as a vehicle) by gavage for eight weeks, respectively. In the in vitro study, the authors subjected the NRK52E cells with or without knock-down Z-DNA binding protein 1(ZBP1) to a high-glucose(HG) environment and various treatments including TFA, EM, and TFA+EM. In the in vivo and in vitro studies, The authors investigated the relative characteristics of renal tubular injury and renal tubular epithelial cells damage induced by reactive oxygen species(ROS), analyzed the relative characteristics of renal tubular PANoptosis and ZBP1-mediatted PANoptosis in renal tubular epithelial cells, and compared the relative characteristics of the protein expression levels of marked molecules of mitochondrial fission in the kidneys and mitochondrial homeostasis in renal tubular epithelial cells, respectively. Furthermore, in the network pharmacology study, the authors predicted and screened targets of TFA and EM using HERB and SwissTargetPrediction databases; The screened chemical constituents and targets of TFA and EM were constructed the relative network using Cytoscape 3.7.2 network graphics software; The relative targets of DT were integrated using OMIM and GeneCards databases; The intersecting targets of TFA, EM, and DT were enriched and analyzed signaling pathways by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG) software using DAVID database. In vivo study results showed that TFA+EM could improve renal tubular injury, the protein expression levels and characteristics of key signaling molecules in PANoptosis pathway in the kidneys, and the protein expression levels of marked molecules of mitochondrial fission in the kidneys. And that, the ameliorative effects in vivo of TFA+EM were both superior to TFA or EM. Network pharmacology study results showed that TFA+EM treated DT by regulating the PANoptosis signaling pathway. In vitro study results showed that TFA+EM could improve ROS-induced cell injury, ZBP1-mediatted PANoptosis, and mitochondrial homeostasis in renal tubular epithelial cells under a state of HG, including the protein expression levels of marked molecules of mitochondrial fission, mitochondrial ultrastructure, and membrane potential level. And that, the ameliorative effects in vitro of TFA+EM were both superior to TFA or EM. More importantly, using the NRK52E cells with knock-down ZBP1, the authors found that, indeed, ZBP1 was mediated PANoptosis in renal tubular epithelial cells as an upstream factor. In addition, TFA+EM could regulate the protein expression levels of marked signaling molecules of PANoptosis by targeting ZBP1. In summary, this study clarified that TFA+EM, different from TFA or EM, could attenuate DT with multiple targets by ameliorating mitochondrial homeostasis and inhibiting ZBP1-mediated PANoptosis. These findings provide the clear pharmacological evidence for the clinical treatment of DT with a novel strategy of TFA+EM, which is named "coordinated traditional Chinese and western medicine".
Animals ; Rats ; Mitochondria/metabolism* ; Benzhydryl Compounds/administration & dosage* ; Glucosides/administration & dosage* ; Abelmoschus/chemistry* ; Male ; Homeostasis/drug effects* ; Flavones/administration & dosage* ; Rats, Sprague-Dawley ; Diabetic Nephropathies/physiopathology* ; Drugs, Chinese Herbal/administration & dosage* ; DNA-Binding Proteins/genetics* ; Humans ; Apoptosis/drug effects*

Objective： To investigate the correlation between pathological features at the positive margins and biochemical recurrence after radical prostatectomy for prostate cancer. Methods： From June 2014 to December 2019, a total of 200 patients with organ-confined prostate cancer who underwent radical prostatectomy were included in this study by the method of case matching (1∶1). One hundred patients with positive surgical margin and 100 with negative surgical margin were enrolled in this study. All patients did not receive any adjuvant treatment after surgery with a clinical stage of T2/N0. BCR-free survival was estimated using the Kaplan-Meier method. An optimal cutoff for the PSM length which differentiated risk for BCR was identified by Classification and Regression Tree analysis (CART). Cox proportional hazards regression model was used to assess the association between variables and BCR-free survival. Results： A total of 200 patients were included in this study, and 177 patients with pT2 stage were pathological after operation. The median follow-up time of this group of patients was 32.8 months ranged from 5.6 to 80.5 months. A total of 28 cases of biochemical recurrence were found through PSA follow-up after surgery, including 6 cases (6.0%) in the negative margin group and 22 cases (22.0%) in the positive margin group. The result of Kaplan Meier survival curve analysis showed that the non biochemical recurrence survival time of the negative margin group was longer than that of the positive margin group (log rank χ2=9.336, P=0.003). It was found that the length of positive margin ≥1 mm in the positive margin group was positively correlated with postoperative biochemical recurrence. Multivariate Cox proportional hazards regression was used to identify that the highest Gleason score ≥8 and the length of positive ≥1 mm were independent factors of postoperative biochemical recurrence in both the overall patients and the patients with positive margin. Conclusion：　The patients with highest Gleason score ≥8 and the length of positive ≥1mm are at elevated risk for BCR.
Humans ; Male ; Prostatectomy ; Prostatic Neoplasms/pathology* ; Neoplasm Recurrence, Local ; Margins of Excision ; Prostate-Specific Antigen/blood* ; Proportional Hazards Models ; Middle Aged ; Aged ; Neoplasm Staging ; Kaplan-Meier Estimate

Objective To analyze the prevalence and genetic characteristics of influenza A(H3N2) viruses in the city of Xiangyang in 2022-2023, and to provide a scientific basis for predicting the epidemic and mutation of influenza virus. Methods Throat swab specimens of the influenza like cases were collected from national influenza monitoring sentinel hospitals in Xiangyang every week. RNA was extracted from the specimens for influenza diagnosing using real-time RT-PCR．Viruses were isolated from H3N2 positive specimens, and HA and NA genes were amplified and sequenced．3D modeling analyses were conducted. Results The gene phylogenetic tree showed that the H3N2 isolates in 2022-2023 belonged to 3C.2a1b.2a1 and 3C.2a1b.2a2 branches, respectively. The A(H3N2) influenza virus strains all had amino acid point mutation sites on important antigenic determinants of HA protein. The epitope mutations of the 2022 A(H3N2) strain mainly occurred in regions B, C, and D. The epitope mutations of the A(H3N2) strain in 2023 mainly occurred in regions C and D. Different glycosylation sites of HA gene were found in 2022-2023 strains. No variation was found in key amino acid sites associated with neuraminidase inhibitor resistance. The difference of overall structure was not obvious in the three-dimensional simulation structure diagram. Conclusion The A(H3N2) influenza strains isolated in this study have shown antigenic drift, especially the mutation of HA, which may affect the protective effect of the vaccine on the local population and lead to influenza epidemic. The variations of HA and NA suggest that close attention should be paid to the epidemic and genetic variation of H3N2 subtype influenza virus, to provide a scientific basis for the selection of influenza virus vaccine strains and the prevention and control of influenza.

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.

Aim To investigate the involvement of mesencephalic astrocyte-derived neurotrophic factor(MANF)in rifampicin(RFP)-induced cholestatic liv-er injury.Methods We investigated the impact of MANF gene deletion on rifampicin-induced BAT ex-pression in mice by the MANF gene knockout mouse model.We investigated the influence of MANF knock-down on nuclear factor erythroid 2-related factor 2(Nrf2)in HepG2 cells by the MANF knockdown cell model.Results Compared with the wild-type(WT)mice,the mRNA and protein expression levels of bile salt export pump(BSEP)and multidrug-resistant asso-ciated protein4(MRP4)significantly increased in WT mice treated with RFP.However,compared to the WT mice treated with RFP,the mRNA and protein expres-sion levels of BSEP,Multidrug resistance protein 1(MDR1),multidrug resistance associated proteins 2/3/4(MRP2/3/4),and organic solute transport pro-teins α(OST α)were significantly reduced.In cell experiments we found that MANF knockdown weakened the expression of Nrf2 and its nuclear translocation by RFP.Conclusion MANF may regulate adaptive BAT expression by modulating Nrf2 expression,thereby pla-ying a protective role in RFP-induced liver injury.

Objective:To investigate the safety and efficacy of excimer laser ablation (ELA) combined with drug-coated balloon (DCB) for the below-the-knee (BTK) artery lesions.Methods:From Jun 2019 to Nov 2022, 22 patients receiving ELA combined with DCB in atherosclerotic lesions of BTK artery at these two centers were retrospectively analyzed.Results:In these 22 patients there were 3 (13.6%) suffering from stenosis and 19 (86.4%) from chronic total occlusion (CTO) lesions. The mean length of lesion was (25.6±5.7) cm. The technical success rate was 95.5%. Flow-limiting dissection was found in 1 (4.5%) patient and a bailout stent was deployed. The mean ankle-brachial index (ABI) significantly improved during the follow-up period compared with that before the treatment. The median follow-up time was 21.5 months. The 1-year primary patency rate was 80.3%Conclusion:ELA combined with DCB was safe and effective in the treatment of atherosclerotic lesions of BTK artery, improving the primary patency.

Objective:To evaluate the effect of botulinum toxin type A (BTXA) on flap surgery in animal models.Methods:Nine databases (PubMed, Cochrane Library, Ovid, Web of Science, Embase, Scopus, CBM, CNKI, and WANFANG database) were searched for published literature comparing the effects of BTXA (BTXA group) versus saline or no treatment (control group) on flap operation in animal models from January 1979 to March 2022. The literature was screened according to inclusion and exclusion criteria. Indicators included flap survival rate, blood flow and vascular endothelial growth factor (VEGF) expression level after surgery. The subjects were divided into pre-operation injection group and intraoperation injection group according to the intervention timing, and were divided into random flap group and axial flap group according to the type of flaps, and subgroup analysis was conducted respectively. Review Manager (RevMan) 5.3 software and Stata 15.1 software were used for all statistical analysis.Results:A total of 603 animals from 19 studies were included after rigorous inclusion and exclusion screening. Compared with control group, BTXA group revealed a significantly higher flap survival rate [mean difference ( MD)=15.65%, 95% CI: 13.11%-18.19%, Z=12.08, P<0.001], blood flow [standardized mean difference ( SMD)=1.96, 95% CI: 1.39-2.54, Z=6.71, P<0.001] and VEGF expression (at mRNA level: SMD=6.01, 95% CI: 0.89-11.13, Z=2.30, P=0.020; at protein level: SMD=3.44, 95% CI: 2.44-4.43, Z=6.73, P<0.001). Subgroup analysis showed that the flap survival rate of the pre-operation injection group ( MD=21.54%, 95% CI: 16.07%-27.01%, Z=7.71, P<0.001) was significantly higher than that of the intraoperative injection group ( MD=9.40%, 95% CI: 6.79%-12.00%, Z=7.07, P<0.001). The flap survival rate of the random flap group ( MD=20.87%, 95% CI: 16.67%-25.07%, Z=9.73, P<0.001) was significantly higher than that of the axial flap group ( MD=13.11%, 95% CI: 8.91%-17.31%, Z=6.12, P<0.001). Conclusion:BTXA assisted flap surgery may have positive effects on the survival rate, blood flow and VEGF expression in animal models. In addition, injection timing and flap type may also be important factors in the effect of BTXA on flap surgery.

Objective:To evaluate the effect of botulinum toxin type A (BTXA) on flap surgery in animal models.Methods:Nine databases (PubMed, Cochrane Library, Ovid, Web of Science, Embase, Scopus, CBM, CNKI, and WANFANG database) were searched for published literature comparing the effects of BTXA (BTXA group) versus saline or no treatment (control group) on flap operation in animal models from January 1979 to March 2022. The literature was screened according to inclusion and exclusion criteria. Indicators included flap survival rate, blood flow and vascular endothelial growth factor (VEGF) expression level after surgery. The subjects were divided into pre-operation injection group and intraoperation injection group according to the intervention timing, and were divided into random flap group and axial flap group according to the type of flaps, and subgroup analysis was conducted respectively. Review Manager (RevMan) 5.3 software and Stata 15.1 software were used for all statistical analysis.Results:A total of 603 animals from 19 studies were included after rigorous inclusion and exclusion screening. Compared with control group, BTXA group revealed a significantly higher flap survival rate [mean difference ( MD)=15.65%, 95% CI: 13.11%-18.19%, Z=12.08, P<0.001], blood flow [standardized mean difference ( SMD)=1.96, 95% CI: 1.39-2.54, Z=6.71, P<0.001] and VEGF expression (at mRNA level: SMD=6.01, 95% CI: 0.89-11.13, Z=2.30, P=0.020; at protein level: SMD=3.44, 95% CI: 2.44-4.43, Z=6.73, P<0.001). Subgroup analysis showed that the flap survival rate of the pre-operation injection group ( MD=21.54%, 95% CI: 16.07%-27.01%, Z=7.71, P<0.001) was significantly higher than that of the intraoperative injection group ( MD=9.40%, 95% CI: 6.79%-12.00%, Z=7.07, P<0.001). The flap survival rate of the random flap group ( MD=20.87%, 95% CI: 16.67%-25.07%, Z=9.73, P<0.001) was significantly higher than that of the axial flap group ( MD=13.11%, 95% CI: 8.91%-17.31%, Z=6.12, P<0.001). Conclusion:BTXA assisted flap surgery may have positive effects on the survival rate, blood flow and VEGF expression in animal models. In addition, injection timing and flap type may also be important factors in the effect of BTXA on flap surgery.

Aim To study the inhibitory effect of attenuated salmonella SGN1, overexpressing methioninase, on nasopharyngeal carcinoma (NPC) and the underlying mechanism. Methods The cell proliferation, cell cycle, cell apoptosis, clony formation and migration a-bility of 5-8F, HNE-2, CNE-2 cells were measured u-sing flow cytometry assay, clone formation assay, and wound assay after the methionine restriction treatment. 5-8F, HNE-2, CNE-2 cells were infected with SGN1 at the multiplicity of infection (MOI) of 1: 100 for 5 hours, followed with the measurement of cell growth. A xenograft model was constructed by subcutaneous injection of 5-8F cells in mice to observe the inhibitory effect of SGN1 on nasopharyngeal carcinoma. Results Compared with the control group, methionine restriction significantly inhibited the proliferation, migration ability, and clone formation of nasopharyngeal carcinoma cells and blocked the G

Objective: To investigate whether admission blood pressure (BP) variability during multiple hospitalizations is associated with all-cause mortality independent of baseline BP in acute decompensated heart failure (ADHF). Methods: Patients with ADHF admitted to the Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University from September 2013 to December 2017 were retrospectively enrolled. The risk of all-cause mortality associated with indices of BP variability, including mean admission BPs, standard deviation of BP and coefficient of variation of BP during multiple hospitalizations was assessed, using Cox regression model. Results: A total of 1 006 ADHF patients (mean aged (69.3±13.5) years; 411 (40.8%) female; 670 (66.6%) with preserved ejection fraction) were enrolled. During a median follow-up of 1.54 years, 47.0% of patients died. In all ADHF patients, after adjusting for confounding factors, for every 1-standard deviation (SD) increase in SD and coefficient of variation (CV) of systolic BP, the risk of all-cause mortality increased by 10% and 11%, respectively (SD: HR, 1.10, 95%CI, 1.01-1.21, P=0.029, CV: HR, 1.11, 95%CI, 1.02-1.21, P=0.017); for every 1-SD increase in the mean of diastolic BP, the risk of all cause mortality decreased by 25% (HR, 0.75; 95%CI, 0.65-0.87; P<0.001). In ADHF patients with preserved ejection fraction, after accounted for potential confounders, higher SD and CV of admitted systolic and diastolic BP were significantly associated with higher risk of all-cause mortality, regardless of whether confounding factors were adjusted (P≤0.049); After adjusting for confounding factors, the risk of all-cause mortality increased by 18% and 19% for every 1-SD increase in SD and CV of systolic BP, while the risk of all-cause mortality increased by 11% and 15% for every 1-SD increase in SD and CV of diastolic BP. In ADHF patients with reduced ejection fraction, after adjusting for confounding factors, the higher the mean admission systolic BP during multiple hospitalizations, the lower the risk of total mortality (HR, 0.68; 95%CI, 0.47-1.00; P=0.049). Conclusions: In patients with ADHF, independent of baseline BP, BP variability during multiple hospitalizations was strong predictor of all-cause mortality.
Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Male ; Blood Pressure ; Retrospective Studies ; Heart Failure ; Hospitalization ; Ventricular Dysfunction, Left ; Risk Factors ; Prognosis