Aim To explore the ameliorative effects of berberine(BBR)on diabetic nephropathy(DN)in mice and investigate its potential mechanisms through transcriptomic analysis.Methods 8-week-old db/db mice were randomly assigned into four groups:model group(DN group),BBR 50 mg·kg-1 group(BBR-L group),BBR 100 mg·kg-1 group(BBR-H group),and empagliflozin 10 mg·kg-1 group(EMPA group).Age-matched db/m mice were used as the control group(NC group),with eight mice in each group.Each group received intragastric administration once daily for eight weeks.After the treatment,serum,u-rine,and kidney samples were collected to evaluate re-nal function indicators and observe renal pathological changes.Differentially expressed genes(DEGs)in kidney tissue were identified through transcriptomic a-nalysis,followed by KEGG and GO enrichment analy-sis.Potential targets were further validated using mo-lecular docking,molecular dynamics simulations,West-ern blot,and immunohistochemistry.Results Both BBR and EMPA significantly reduced fasting blood glu-cose levels in DN mice,improved renal function,and alleviated renal injury and fibrosis.Compared to the NC group,855 DEGs were identified in the DN group,while 194 DEGs were identified in the BBR-H group compared to the DN group.KEGG enrichment analysis indicated that the mechanisms underlying BBR's effects on DN were primarily related to type 1 diabetes and bile secretion pathways.Molecular docking results demonstrated a strong binding affinity between BBR and FXR and a moderate binding affinity with SHP.Molecular dynamics simulations corroborated the doc-king results.FXR and SHP protein expression signifi-cantly decreased in the DN group compared to the NC group.At the same time,BBR treatment significantly increased the expression of these proteins compared to the DN group.Conclusion BBR may mitigate DN-in-duced renal injury by modulating bile acid and lipid homeostasis through the FXR-SHP pathway.

Objective To investigate the effect of miR-519e-5p targeting Annexin A5(ANXA5)on the biological behavior of chordoma U-CH1 cells.Methods The expressions of miR-519e-5p and ANXA5 in human chordoma tissues and adjacent tissues were detected by qRT-PCR.U-CH1 cells were cultured in vitro and divided into miR-519e-5p mimics group,miR-519e-5p mimics negative control+empty vector group,miR-519e-5p mimics+ANXA5 overexpression group,and control group.The proliferation of U-CH1 cells in each group was detected by plate colony formation assay and MTT assay;flow cytometry was used to detect the apoptosis of U-CH1 cells in each group;the migration and invasion of U-CH1 cells in each group were detected by scratch would healing assay and Transwell assay respectively;the expression of ANXA5 protein,apoptosis-related proteins(Bcl-2,Bax)and migration epithelial-mesenchymal transition-related proteins(Claudin-1,Vimentin,E-cadherin)of U-CH1 cells in each group were detected by Western blot;the expression of miR-519e-5p and ANXA5 mRNA of U-CH1 cells in each group was detected by qRT-PCR;and the interaction between miR-519e-5p and ANXA5 in U-CH1 cells was examined by dual-luciferase reporter gene assay.Results Compared with the adjacent tissues,the expression of miR-519e-5p in chordoma tissues decreased(P<0.05),and the expression of ANXA5 mRNA increased(P<0.05).Compared with the control group,the cell proliferation rate,colony formation rate,migration rate,invasion number,expressions of ANXA5 mRNA and ANXA5,Bcl-2,Claudin-1,and Vimentin proteins in the miR-519e-5p mimics group decreased(P<0.05),the expression of miR-519e-5p mRNA,the apoptosis rate,and the expression of Bax and E-cadherin proteins increased(P<0.05).Compared with the miR-519e-5p mimics group,the colony formation rate,cell proliferation rate,invasion number,migration rate,expressions of ANXA5 mRNA and ANXA5,Bcl-2,Vimentin,and Claudin-1 proteins in the miR-519e-5p mimics+ANXA5 overexpression group increased(P<0.05),and the apoptosis rate,the expression of Bax and E-cadherin proteins decreased(P<0.05).MiR-519e-5p can target and down-regulate the expression of ANXA5 in U-CH1 cells.Conclusion MiR-519e-5p reduces the migration,proliferation and invasion viability of chordoma U-CH1 cells,and promotes apoptosis by targeting the inhibition of ANXA5 expression.

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.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

Objective:To explore the effect of nursing intervention based on the integrated theory of health behavior change on the compliance of patients with obstructive sleep apnea hypopnea syndrome (OSAHS) with continuous positive airway pressure (CPAP) treatment.Methods:From February 2023 to January 2024, convenience sampling was used to select 98 patients with moderate to severe OSAHS from the Sleep Center of Affiliated Wuxi Fifth Hospital of Jiangnan University as participants. Patients were divided into a control group and an experimental group based on their enrollment time, with 49 cases in each group. Control group received routine nursing, while experimental group was treated with nursing intervention based on the integrated theory of health behavior change. The compliance with CPAP was compared between two groups after three months of intervention, and the subjective daytime drowsiness, self-efficacy, social support, and quality of life were compared between the two groups before and after intervention.Results:After intervention, the compliance with CPAP in experimental group was higher than that in control group, and daytime sleepiness, self-efficacy, social support, and quality of life scores in experimental group were all better than those in control group, with statistical differences ( P<0.05) . Conclusions:Nursing intervention based on the integrated theory of health behavior change can increase compliance of OSAHS patients with CPAP, alleviate daytime sleepiness, enhance self-efficacy and social support, and improve quality of life.

Alzheimer's disease(AD)is a neurodegenerative disease with age-related cognitive decline.Sphingosine-1-phosphate receptor 2(S1PR2)is involved in a variety of cellular processes and has been shown to play an important role in nervous system development.This study aimed to investigate the effects and possible mechanism of S1PR2 on Aβ25-35 induced cell model damage of AD.In this study,SH-SY5Y cells were induced by Aβ25-35 to construct a cell damage model,and the expression of S1PR2 in cells was interfered by targeting sequence.The protein and gene expression levels of S1PR2 were detected by Western blot and RT-PCR.It was found that the expression of S1PR2 was significantly increased at mR-NA and protein levels in Aβ25-35-induced SH-SY5Y cell model(P＜0.01),and its expression was signifi-cantly decreased after S1PR2 intervention(P＜0.001).The cell proliferation activity was detected by CCK8,and apoptosis was detected by flow cytometry.The results showed that the proliferation activity of Aβ25-35 induced SH-SY5Y cells was significantly increased,and apoptosis was decreased after S1PR2 in-tervention(P＜0.01).The protein levels of APP,Tau,p-Tau,and PSD95 in cells were detected by Western blot to analyze the effect of S1PR2 on the pathology of AD.It was found that after S1PR2 inter-vention,the expressions of APP,Tau,and p-Tau in the AD cell model were significantly decreased(P＜0.001),and the expression of synaptic protein PSD95 was increased(P＜0.001),which could signifi-cantly improve the pathological damage in Aβ25-35-induced SH-SY5Y cell model.In addition,ATP pro-duction was detected by the kit,and ROS content and mitochondrial membrane potential were detected by flow cytometry to analyze the mitochondrial function.Results found that ATP production and mitochondri-al membrane potential was significantly decreased,whereas the ROS content was increased in Aβ25 35 in-duced SH-SY5Y cells(P＜0.001).Intervention with S1PR2 significantly increased ATP production and mitochondrial membrane potential,but decreased ROS content(P＜0.001).Finally,the protein levels of the AKT/mTOR pathway were detected by Western blot.The results showed that S1PR2 significantly in-hibited the activation of the AKT/mTOR pathway induced by Aβ25-35 in SH-SY5Y cells.In conclusion,S1PR2 may be involved in the pathogenesis of Aβ25-35-induced SH-SY5Y cells by promoting mitochondrial function through the AKT/mTOR pathway.

Objective:To discover the relationship between the RNF213 gene and acute myeloid leukemia(AML),and explore the effect of RNF213 on the proliferation and apoptosis of THP-1 cells.Methods:Analyze the expression of RNF213 gene in AML and its relationship with prognosis through the GEPIA database.Collecting 30 AML patients and non-tumor hematological patients who went to the Affiliated Hospital of Zunyi Medical University from January 2017 to January 2022.RT-qPCR and Western blot were used to detect the expression levels of RNF213 mRNA and protein.Perform survival of patients was analysed by Kaplan-Meier.Meanwhile,the expression levels of RNF213 mRNA and protein were detected in AML cell lines(THP-1,OCI-AML2).CRISPR-Cas9 was used to knockdown the RNF213 gene in THP-1 cells;flow cytometry was used to detect apoptosis rate of cell.CCK-8 and colony formation assay were used to detect cell proliferation.Western blot was used to detect the expression level of Cleaved-Caspase 3 protein.Results:Compared with the control group,the expression level of RNF213 in AML patients was significantly increased,and patients with high expression of RNF213 have a worse prgnosis.Higher expression level of RNF213 protein in THP-1 cells.After knocking down the RNF213 gene of THP-1 cells,cell proliferation was significantly reduced,and the apoptosis rate and expression of apoptosis related protein Cleared-Caspase3 were significantly increased.Conclusion:AML patients have high expression of RNF213,and the prognosis of high expression patients is poor.The RNF213 gene affects AML cell proliferation and apoptosis,and may be a prognostic marker and potential therapeutic target for AML.

Objective:To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with CEBPA-bZIP mutation. Methods:Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with CEBPA-bZIP mutation. The nomogram model for leukemia-free survival (LFS) rate was generated by combining genetic abnormalities and clinical data. Risk stratification was conducted based on prognostic variables and the effect of risk-adjusted consolidation therapy was investigated by Kaplan-Meier method. Results:Four variables were finally included in our nomogram model after multivariate Cox analysis,and an equation for risk score calculation was obtained,risk score=1.3002×white blood cell (WBC) (≥18.77×109/L)+1.4065×CSF3R mutation positive+2.6489×KMT2A mutation positive+1.0128×DNA methylation-related genes mutation positive. According to the nomogram model,patients were further divided into low-risk group (score=0,n=46) and high-risk group (score>0,n=95). Prognostic analysis showed that the 5-year LFS rate,5-year overall survival (OS) rate,and 5-year cumulative incidence of relapse (CIR) of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the high-risk group were 93.5％,97.1％,and 3.5％,while those in patients who received maintenance chemotherapy were 32.9％,70.5％,and 63.4％,respectively. The differences were statistically significant (all P<0.05). Allo-HSCT could significantly improve the prognosis of patients in high-risk group. However,no corresponding benefit was observed in the low-risk group. Conclusion:Adult CN-AML with CEBPA-bZIP mutation has a complex co-mutation pattern. The nomogram model based on mutations of CFS3R,KMT2A and DNA methylation-related genes together with WBC count can further divide this subset of patients into a relatively low-risk group and a relatively high-risk group. For individuals in the high-risk group,allo-HSCT is proposed as post-remission therapy. The above data will benefit the prognosis estimation and treatment decision for adult CN-AML with CEBPA-bZIP mutation.

Objective:To explore the changes in number and immune function of mucosal-associated invariant T (MAIT) cells in peripheral blood of patients with newly diagnosed acute myeloid leukemia (AML),and its correlation with the occurrence and development of AML. Methods:Seventy-five clinical samples of patients with newly diagnosed AML and 48 healthy control samples in our hospital from January 2022 to February 2023 were included. Multiparametric flow cytometry was used to detect the number of MAIT cells,membrane surface markers,effector phenotypes and functional indicators in the samples. Results:Compared with healthy controls,the percentage of MAIT cells in CD3+T cells in peripheral blood of newly diagnosed AML patients was significantly reduced (P<0.001). The percentage of MAIT cells in all CD3+T cells in bone marrow of AML patients was similar to that in peripheral blood (P>0.05). Most of MAIT cells in peripheral blood of AML patients were effector memory T cells. Compared with healthy controls,the proportion of effector memory MAIT cells decreased (P<0.05),while the proportion of terminally differentiated effector memory MAIT cells and PD-1+MAIT cells increased significantly (both P<0.05). AML patients' peripheral blood MAIT cells expressed significantly higher levels of granzyme B and perforin than healthy controls (both P<0.05),and secreted significantly lower levels of cytokines such as gamma interferon and tumor necrosis factor α than healthy controls (both P<0.001). Conclusion:Compared with healthy controls,the proportion of MAIT cells in AML patients is reduced and the expression of functional markers is abnormal,suggesting that their function is impaired and may be involved in the occurrence and development of AML.

Objectives:To explore the feasibility of using hemodynamic phenotypes to guide antihypertensive treatment medication. Methods:This study prospectively included 100 hypertensive patients who received outpatient treatment at Haidian Hospital in Beijing from January 2021 to December 2021.Evaluation of blood pressure was conducted using laboratory and home blood pressure measurements,impedance cardiogram(ICG)detection was performed.Following hemodynamic phenotypes and therapeutic phenotypes were established:hyperkinetic phenotype(increased heart rate)using β-blockers,large artery phenotype(increased large artery resistance index)using calcium antagonists,peripheral vascular phenotype(increased peripheral vascular resistance index)using renin angiotensin system inhibitors,and high-volume phenotype(increased blood volume saturation)using diuretics.Patients were randomly divided into ICG group(n=50,medication treatment based on hemodynamic characteristics)and control group(n=50,treatment based on hypertension guidelines and clinical experience).Patients were followed up for 8 weeks and the blood pressure reduction amplitude and compliance rate were compare between the two groups. Results:There was no statistically significant difference in baseline data such as sex,age,height,weight,and hemodynamic parameters between the two groups(all P＞0.05).There was no statistically significant difference in the types of baseline medication between the two groups(P＞0.05).After medication adjustment,the types of medication increased,but the difference between the two groups was still not statistically significant(P＞0.05).Clinic blood pressure:After 8 weeks,decreases in systolic([8.38±27.78]mmHg,1 mmHg=0.133 kPa)and diastolic([3.94±18.15]mmHg)blood pressure were greater in the ICG group as compared to the control group(both P＜0.05).The blood pressure compliance rate(＜140/90 mmHg)was higher in the ICG group than that in the control group(66.0%vs.42.0%,P＜0.05).Family blood pressure:after 8 weeks,the reduction in systolic([8.22±21.31]mmHg,P＜0.01)and diastolic([4.76±13.88]mmHg,P＜0.05)blood pressure was greater in the ICG group compared to the control group.The blood pressure compliance rate(＜135/85 mmHg)was higher in the ICG group than that in the control group(70.0%vs.48.0%,P＜0.05).Changes in corresponding hemodynamic parameters before and after two different antihypertensive drugs:the heart rate,arterial resistance index,peripheral vascular resistance index,and blood volume saturation of the ICG group all significantly decreased compared to baseline(all P＜0.05).The control group showed a significant decrease in peripheral vascular resistance index compared to baseline(P＜0.05),while there was no statistically significant difference in heart rate,large artery resistance index,and blood volume saturation compared to baseline(all P＞0.05). Conclusions:By using impedance cardiogram to assess hemodynamic phenotypes and accurately guide the selection of antihypertensive drugs based on hemodynamic phenotypes,it is possible to more effectively lower blood pressure and improve blood pressure compliance.