Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

OBJECTIVES: To explore the therapeutic mechanism of puerarin for alleviating synovitis in rats with collagen-induced arthritis (CIA). METHODS: In a SD rat model of CIA, we tested the effects of daily gavage of puerarin at low, moderate and high doses (10, 30, and 100 mg/kg, respectively) for 3 weeks, with tripterygium glycosides (GTW, 10 mg/kg) as the positive control, on swelling in the hind limb joints regions evaluated by arthritis index scoring. Mass fraction of the liver of the rats was calculated, and pathologies in joint synovial membrane were observed with HE staining. The expressions of transforming growth factor β‑activated kinase-1 (TAK1), Toll-like receptor 4 (TLR4), and nuclear factor kappa-Bp65 (NF‑κB p65) at the mRNA and protein levels in the synovial tissues were detected using Real-time PCR and Western blotting. RESULTS: Compared with those in the model group, the rats in GTW group and high-dose puerarin group showed significantly reduced mass fraction of the liver. Treatment with GTW and puerarin at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, and improved synovitis in CIA rats (P<0.05), and the effects of puerarin showed an obvious dose dependence. Both GTW and puerarin treatments significantly lowered TAK1, TLR4, and NF‑κB p65 mRNA and protein expressions in the synovium of CIA rats. CONCLUSIONS Puerarin alleviates synovium damages in CIA rats possibly by suppressing the TLR4/NF‑κB signaling pathway via downregulating TAK1 expression.
Animals ; Toll-Like Receptor 4/metabolism* ; Rats, Sprague-Dawley ; Rats ; MAP Kinase Kinase Kinases/metabolism* ; Signal Transduction/drug effects* ; Arthritis, Rheumatoid/drug therapy* ; NF-kappa B/metabolism* ; Isoflavones/therapeutic use* ; Male ; Arthritis, Experimental/drug therapy* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/metabolism*

Objective To analyze the risk factors of fluconazole resistance in Candida tropicalis(C.tropicalis)urinary tract infection(UTI),and evaluate the efficacy of different treatment regimens.Methods Patients with C.tropicalis UTI at Xiangya Hospital of Central South University from January 2021 to December 2023 were in-cluded for single center retrospective study.The minimum inhibitory concentration(MIC)of fluconazole was deter-mined by microbroth dilution.Patients were divided into a fluconazole-resistant group and a fluconazole-sensitive group based on fluconazole resistance.Risk factors for fluconazole resistance were analyzed based on clinical data,and therapeutic efficacy in patients in fluconazole-resistant group was analyzed.Results A total of 198 patients were included in the study.133(67.2％)C.tropicalis strains were detected to be sensitive to fluconazole,while 65(32.8％)strains were resistant,and 63.1％(n=41)had MIC values ≥128 μg/mL.Compared with fluconazole-sensitive group,fluconazole-resistant group had a higher proportion of pulmonary infection(P=0.019).Pulmonary infection(OR=3.282)was a risk factor for fluconazole resistance in C.tropicalis UTI,while urinary system ob-struction(OR=0.269)was a protective factor for fluconazole resistance in C.tropicalis UTI.There was no statis-tically significant difference in the usage rate of different antimicrobial agent types between the two groups(all P＞0.05).The therapeutic efficacy analysis showed that the effective rates of treatment with fluconazole dosage regi-mens of ≤200 mg/d,≥400 mg/d,and fluconazole monotherapy against fluconazole-resistant strains were 66.7％(6/9),83.3％(5/6),and 100％(6/6),respectively.For patients treated with monotherapy using other drugs or with multidrug sequential treatment regimens,the treatment effective rate was 60.0％(3/5).The proportion of pa-tients in the effective treatment group who removed their urinary catheters after detecting C.tropicalis was higher than that in the ineffective treatment group(P＜0.001).Conclusion The fluconazole resistance of C.tropicalis is related to urinary tract obstruction and concurrent pulmonary infection.When treating UTI caused by fluconazole-resistant strains,the catheter should be removed as early as possible.In addition to increasing the dosage of flucon-azole,other antifungal drugs such as flucytosine alone or sequential treatment with multiple drugs can also be con-sidered.

Objective To explore the application of problem solving mode based on self-regulation theory in maintenance hemodialysis(MHD)patients.Methods The convenient sampling method was used to enroll the patients who underwent hemodialysis in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January to October 2022.According to the random number table,they were assigned to the control group or observation group.Routine nursing was used in the control group,and the nursing care of problem-solving mode based on self-regulation theory was applied in the observation group for 4 week.Self-management behavior,volume management behavior,disease perception and learned helplessness were compared between the two groups at 4 and 12 weeks after intervention.Results Eight patients(5 cases in the control group and 3 cases in the observation group)failed to be followed up.There was no significant difference in the score of self-management behavior,volume management behavior,disease perception or learned helplessness between the two groups before the intervention(P＞0.05).At 4 and 12 weeks after the intervention,the scores of self-management behavior and volume management behavior in the observation group were significantly higher than those in the control group,while the scores of disease perception and learned helplessness in the observation group were significantly lower than those in the control group(P＜0.05).Conclusion The problem-solving mode based on self-regulation theory can improve self-management and volume management of MHD patients,reduce negative disease perception and learning helplessness,and achieve continuous improvement in cognition,psychology and behavior after the intervention.

Objective:To investigate the influence of inner cell mass and trophectoderm cytoplasmic strings during blastocyst expan-sion on embryonic development and pregnancy outcome.Methods:A retrospective cohort analysis was performed for the clinical data of patients who received pre-implantation genetic testing for aneuploidy(PGT-A)and underwent single blastocyst transplantation in our hospital from June 2019 to December 2021.A total of 530 patients were enrolled,and genetic testing was performed for 2132 blasto-cysts.According to the presence or absence of cytoplasmic strings during blastocyst expansion,the blastocysts were divided into cyto-plasmic strings(+)group with 534 blastocysts and cytoplasmic strings(-)group with 1598 blastocysts,and quality and PGT-A results were compared between the two groups.After the transfer of euploid blastocysts,pregnancy outcome was compared between the 115 blastocysts with cytoplasmic strings and the 415 blastocysts without cytoplasmic strings.Results:The rates of cytoplasmic strings(+)in the high-,average-,and low-quality blastocyst groups were 30.19%,24.62%,and 12.63%,respectively.The correlation analysis showed a correlation coefficient of-0.115(P<0.001)between embryo quality and the rate of cytoplasmic strings(+).There was no sig-nificant difference in euploidy rate between the two groups(45.3%vs.44.6%).There were no significant differences between the euploid blastocysts with cytoplasmic strings and those without cytoplasmic strings in implantation rate(72.17%vs.66.02%,P=0.213),miscarriage rate(14.46%vs.12.77%,P=0.691),and live birth rate(61.74%vs.57.59%,P=0.424).Conclusion:The presence of cyto-plasmic strings is associated with the morphological quality of blas-tocysts,while it has no impact on embryo ploidy or clinical outcome after euploid embryo transfer.Further research is needed to confirm the impact of cytoplasmic strings on embryonic development.

With the continuous deepening of medical insurance payment reform, the implementation of the ambulatory patient groups(APG) based point system for payment has posed new challenges to the quality management of outpatient electronic medical record writing, as well as the supervision and operation management of outpatient costs in hospitals. A certain hospital began information technology construction in July 2021. By introducing diagnostic grouping functions into the outpatient electronic medical record system, the hospital strengthened the standardization of medical record writing. It also established an intelligent audit system for medical insurance costs to conduct full-process supervision of outpatient medical expenses and developed an intelligent operation analysis system for outpatient APG to provide a basis for hospital operation management decisions and performance distribution. These measures effectively improved the quality of outpatient medical record, reduced outpatient medical costs, and optimized their structure. The application of the intelligent medical insurance audit system also effectively prevented certain non-compliant issues in medical insurance payments, which can provide a reference for other medical institutions.

OBJECTIVE To analyze the manager post competency evaluation scale in central sterile supply depart-ment based on the iceberg model and test its reliability and validity.METHODS A pool of items was constructed based on literature research and semi-structured interviews.The scale was further refined through expert meetings and a pilot survey.A convenience sampling method was used to select 362 managers from central sterile supply de-partments in medical institutions at various levels in Hunan Province in Jan.2024 as survey subjects.Question-naires were administered,and the reliability and validity of the scale were tested.RESULTS The final version of the scale encompassed five dimensions:personal traits,management abilities,professional abilities,other abili-ties,professional knowledge and skills,with a total of 39 items.The item-level validity coefficients of the scale ranged from 0.83 to 1.00,and the content validity index was 0.93.Exploratory factor analysis revealed a Bartlett's test value of 4 723.828(P＜0.001),a KMO test coefficient of 0.937 and a cumulative variance explanation rate of 74.34％for the five common factors.Confirmatory factor analysis results indicated that the root mean square error of approximation(RSEMA)was＜0.08,the root mean square residual(RMR)was＜0.05,and both the incre-mental fit index(IFI)and comparative fit index(CFI)were＞0.9.The Cronbach's α coefficient of the scale was 0.977,the split-half reliability was 0.955,and the test-retest reliability was 0.952.CONCLUSIONS The manager post competency evaluation scale in central sterile supply departments developed in this study demonstrates rela-tively good reliability and validity.It can effectively evaluate manager post competency and provide references for improving related evaluation systems and optimizing training programs.

Objective:To analyze the variation trends in the levels of apolipoprotein B (ApoB), the ratio of apolipoprotein B to low-density lipoprotein cholesterol (ApoB/LDL-C), and non-high density lipoprotein cholesterol (non-HDL-C) among patients and individuals undergoing physical examinations at Zhongshan Hospital, Fudan University from 2014 to 2024.Methods:Data on ApoB, LDL-C, and nonHDL-C levels were collected from individuals (the overall population) who visited or underwent physical examinations at our hospital from January 1, 2014 to December 31, 2024, as well as from individuals (the fixed population) who were tested annually over the 11-year period. The Mann-Kendall test combined with Sen slope estimation was used to analyze the trends. The abnormal rates of ApoB and non-HDL-C in both the overall and fixed populations, as well as the changes in the first and last test results over the 11 years in the fixed population, were also analyzed.Results:The overall population totaled 1 679 440 cases, aged 57 (45, 67) years, and 718 738 cases (42.8%) were female, of which 1 250 234 cases (74.4%) were in the patient population and 429 206 cases (25.6%) were in the health check population. The fixed population of 1 560 cases was 56 (45, 65) years old and 655 cases (42.0%) were female, of which 1 044 cases (66.9%) were in the patient population and 516 cases (33.1%) in the health check population. Between 2014 and 2024, the overall population ApoB decreased from 0.842 g/L to 0.822 g/L (Sen slope -0.001 g·L -1·year -1, P=0.01), the abnormality rate decreased from 24.70% to 22.03% (Sen slope -0.50%/year, P=0.06), and 69.4% of the fixed population showed no change in the subgroups of initial and final tests. ApoB/LDL-C increased from 0.824 to 0.868 (Sen slope -0.003/year, P=0.72). Non-HDL-C decreased from 3.46 mmol/L to 3.32 mmol/L (Sen slope 0.018 mmol·L -1·year -1, P=0.35), with a statistically significant upward trend since 2019 (Sen slope 0.037 mmol·L -1·year -1, P=0.008), and the anomaly rate decreased from 24.3% to 22.7% (Sen slope 0.55%/year, P=0.64), with a statistically significant upward trend since 2019 (Sen slope 1.53%/year, P=0.014), and no change in the grouping of the first and last tests in 75.0% of the fixed population. The trends in the above items were consistent between the overall population and the fixed population. 20-<40 year olds had the most significant upward trend in non-HDL-C along with the least significant downward trend in ApoB/LDL-C and ApoB. Conclusion:ApoB in the overall and fixed populations from 2014-2024 in a Shanghai hospital showed a decreasing trend, and non-HDL-C and abnormality rates showed an increasing trend from 2019 onwards.

OBJECTIVE To investigate the neuroprotective effects of Ditan Decoction(DTD)on ischemic stroke.METHODS A mouse middle cerebral artery occlusion(MCAO)model was used to induce cerebral ischemia and assess the role of DTD in post-stroke NVU injury.DTD was gavaged once a day for 3 days after MCAO.Transwell neutrophil chemotaxis assay was used to explore the role of DTD in the neutrophil chemotaxis.RESULTS In the MCAO model,DTD treatment significantly reduced infarct volume(P<0.01)and attenuated blood-brain barrier disruption,as evidenced by decreased IgG leakage and preserved laminin expression(P<0.05).Furthermore,DTD suppressed neutrophil infiltration into ischemic brain tissue,as demonstrated by reduced neutrophil elastase(P<0.01)and myeloperoxidase(P<0.05)levels.Mechanistically,DTD inhibited neutrophil chemotaxis in a dose-dependent manner and downregulated phosphodiesterase 4B(PDE4B),a key regulator of neutrophil migration(P<0.05).Molecular docking analysis i-dentified four active DTD components-apigenin,vitexin,chlorogenic acid,and orientin-with strong binding affinities to PDE4B(bind-ing energies<-5 kcal·mol-1),suggesting their potential role in mediating DTD's therapeutic effects.CONCLUSION These find-ings highlight DTD as a promising intervention for ischemic stroke,targeting NVU preservation and PDE4B-dependent neutrophil mod-ulation.

Objective:To explore the association between the systemic immune-inflammation index (SII) and obesity metabolic phenotypes, as well as metabolic features in children and adolescents.Methods:A cross-sectional study was conducted using the random cluster sampling method from March 2023 to May 2024. Children and adolescents aged 9-17 years in Guangzhou were surveyed through questionnaires, physical measurements, and blood tests. According to BMI and metabolic status, participants were classified into normal-weight groups [metabolically healthy normal weight (MHNW) and metabolically unhealthy normal weight (MUNW)] and overweight/obese groups [metabolically healthy overweight/obese (MHO/O) and metabolically unhealthy overweight/obese (MUO/O)]. After natural log-transformation of SII values (lnSII), multinomial logistic regression was used to assess the association between SII and obesity metabolic phenotypes, while binary logistic regression was applied to assess the relationship between SII and metabolic phenotypes in the overweight/obese subgroup. Linear regression model and restricted cubic spline (RCS) were employed to examine the relationship between SII and metabolic features among the entire population.Results:A total of 3 749 participants were included. After adjusting for covariates, for every unit increase in lnSII, the risk of MHO/O and MUO/O increased by 93% ( OR=1.93, 95% CI: 1.56-2.40, P<0.001) and 156% ( OR=2.56, 95% CI: 2.02-3.25, P<0.001), respectively. In the overweight/obesity subgroup, for every unit increase in lnSII, the risk of MUO/O increased by 37% ( OR=1.37, 95% CI: 1.01-1.87, P=0.045). Linear regression model and RCS showed that lnSII was positively correlated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (SBP: β=1.39, 95% CI: 0.67-2.11, P<0.001; DBP: β=1.27, 95% CI: 0.79-1.75, P<0.001). lnSII also had a non-linear relationship with triglyceride ( Pnonlinear=0.032) and high-density lipoprotein cholesterol ( Pnonlinear=0.002). Conclusion:Elevated SII levels are associated with unfavorable obesity metabolic phenotypes, higher blood pressure, and altered lipid profiles in children and adolescents. SII may be a potential driving factor for metabolic heterogeneity in children and adolescents.