Aim To clarify the mechanism by which Qishen Yixin Granules improved microcirculation vas-cular endothelial dysfunction(VED)in mice,through activating the Nrf2/HO-1 signaling pathway to regulate oxidative stress.Methods C57 mice were randomly divided into six groups:blank group,model group,pos-itive drug group,and low-,medium-,and high-dose groups of Qishen Yixin Granules.The VED model was established by long-term infusion of Ang Ⅱ combined with a high-fat diet.Each treatment group received the corresponding drug intervention.After four weeks of drug intervention,cardiac function was assessed by echocardiography.Carstairs staining was used to ob-serve the formation of microthrombi in myocardial tis-sue.The micro vascular ischemia was evaluated by Hei-denhain staining.The ultrastructure of endothelial cells was observed by electron microscopy.The levels of EMPs,ROS,NO,ET-1,TF,TM,VWF,and TXA2 in serum were measured by ELISA.The expression levels of MDA,SOD,and GSH-Px in mouse heart tissue were determined by chemical methods.Cardiac microvascu-lar density and the expression of Nrf2,Keap1,and HO-1 proteins were detected by Immunohistochemical stai-ning.The protein expressions of Keap1,cytoplasmic Nrf2,nuclear Nrf2,and HO-1 in myocardial tissue were detected by Western blot.Results Qishen Yixin Granules could effectively improve the cardiac function of mice,alleviate the damage of endothelial cells and endothelial function.They could up-regulate serum NO levels and the activities of antioxidant enzymes SOD and GSH-Px,while down-regulating the expression of ROS and vascular inflammatory injury factors such as ET-1,VWF,TXA2,TF,TM,and EMPs.Qishen Yixin Granules also increased the positive counts of CD34,Nrf2,and HO-1,as well as microvessel density.Fur-thermore,they inhibited the expression of MDA,Keap1,and cytoplasmic Nrf2 protein in myocardial tis-sue,while increasing the expression of nuclear proteins HO-1 and Nrf2.Conclusions Qishen Yixin Granules may inhibit oxidative stress and inflammatory response by regulating the Nrf2/HO-1 signaling pathway,thereby improving vascular endothelial damage and cardiac function in VED mice.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective:To review the literature on surrogate decision making in stroke patients, and to clarify the application status of proxy decision making in stroke patients.Methods:Using the scope review guide as the methodological framework, studies on the application of surrogate decision in stroke patients, PubMed, Medline, CINAHL, Web of Science, Cochrane Library, CNKI, Wanfang, China Biology Medicine databases were searched from the database inception to January 12, 2024.Results:A total of 20 articles were included, including 12 cross-sectional studies, 6 qualitative studies, 1 cohort study, and 1 case report. At present, surrogate decision was mainly used in brain surgery, tube placement and comfort care. The agent had a complicated mood when making a decision and self-doubt after making a decision. Agency decision making was susceptible to demographic factors, disease-related factors, cultural factors, emotional and psychological factors and other factors. Although the outcomes of most proxy decisions were in line with patient preferences, there was a difference in the estimates of prognosis between agents and medical staff.Conclusions:Proxy decision making is widely used in the field of stroke, but the psychological burden of agents is heavy. Developing advance care planning for stroke patients and developing decision aids may help agents make the best decision.

Objective:To investigate the impact of olanzapine and risperidone on the cognitive function, sensory gating function and clinical symptoms of patients with first-episode schizophrenia(FES).Additionally, to analyze the correlation between sensory gating inhibitory deficits and cognitive impairment in FES patients.Methods:A total of 71 FES patients were selected in the Third People's Hospital of Zhongshan City from March 2023 to March 2024, and 60 healthy controls were recruited during the same period.The FES patients were divided into olanzapine group and risperidone group by random number table.Olanzapine group was treated with variable doses of olanzapine(10-20 mg/d), and risperidone group was treated with variable doses of risperidone(3-6 mg/d).The MATRICS consensus cognitive battery(MCCB) was used to evaluate the cognitive function of the patients, P50 index was measured by auditory paired condition-stimulus paradigm, and the efficacy was evaluated by positive and negative syndrome scale(PANSS) score reduction rate before and after 6 weeks of treatment.Healthy controls were assessed cognitive function only once with P50.SPSS 25.0 software was used for data processing. Perform statistical analysis using paired sample t-test, Wilcoxon signed rank test, independent sample t-test, Mann Whitney U test, χ2 test and generalized linear model. Results:Before treatment, the S2 amplitude of FES (1.74 (0.91, 2.79) μV) was higher than that of healthy controls (1.70 (1.04, 2.71) μV) (Wald χ2=4.483, P=0.034), the S2/S1 ratio of FES (0.58 (0.43, 0.78)) was higher than that of healthy controls (0.41 (0.31, 0.57)) (Wald χ2=10.909, P=0.001), and the difference of FES amplitude of S1-S2 was (1.22 (0.43, 1.92) μV) was lower than that of healthy controls (2.23 (1.54, 3.07) μV) (Wald χ2=17.679, P<0.001). There was no significant difference in PANSS, MCCB and P50 between olanzapine group and risperidone group before treatment (all P>0.05). After treatment, there was no significant difference in response rate between the two groups ( χ2=0.059, P=0.808), the PANSS scores were lower than those before treatment, the MCCB test results were higher than those before treatment (both P<0.05), and the P50 results were not statistically significant different compared with those before treatment (both P>0.05). The generalized linear model showed that the S1, S2 amplitude of the P50 had positive impact on the connection test score in the MCCB test ( β=0.466, P=0.020; β=0.879, P=0.009), other indicators were not found to have an impact on the test scores of the MCCB test (all P>0.05). Conclusion:Olanzapine and risperidone can significantly improve the cognitive function of FES, but the improvement of sensory gating deficits is limited. The pathogenic mechanism of sensory gating inhibitory deficits in FES may be different from that of cognitive dysfunction.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To investigate the expression of microRNA-508-3p(miR-508-3p)in epithelial ovarian cancer(EOC)tissue,its impact on the migration and invasion of ovarian cancer cells,and its regulatory relationship with zinc-finger E-box-binding homeobox 1(ZEB1).Methods The surgical resection of EOC cancer tissues and paired adjacent normal tissues were collected.SKOV3 cells were divided into the NC mimic group(transfected with NC mimic),miR-508-3p mimic group(transfected with miR-508-3p mimic),si-NC group(transfected with si-NC),si-ZEB1 group(transfected with si-ZEB1)and co-transfection group(co-transfected with si-ZEB1 and miR-508-3p mimic).The mRNA expression levels of miR-508-3p and ZEB1 in EOC cancer tissues,adjacent normal tissues and five groups of cells were measured by real-time quantitative polymerase chain reaction.The Transwell assay was used to detect the cell migration and invasion abilities.Results The relative expression levels of miR-508-3p in EOC tissues and adjacent normal tissues were 0.77±0.36 and 1.07±0.40,the relative expression levels of ZEB1 mRNA in EOC tissues and adjacent normal tissues were 2.10±1.21 and 1.29±0.95,and the differences were statistically significant(all P＜0.01).The migration cell number of the NC mimic,miR-508-3p mimic,si-NC,si-ZEB1 and co-transfection groups was 633.00±32.49,319.20±19.89,650.40±25.85,375.00±17.25 and 129.40±17.10;the invasion cell number was 527.20±25.01,288.60±16.68,520.00±25.83,293.40±18.37 and 76.60±8.76;the relative expression levels of miR-508-3p were 1.05±0.37,3.94±1.21,1.01±0.21,1.26±0.34 and 3.40±0.41;the relative expression levels of ZEB1 mRNA were 1.00±0.04,0.58±0.05,1.00±0.08,0.54±0.07 and 0.29±0.03,respectively.The above indicators showed statistically significant differences between the miR-508-3p mimic group and the NC mimic group,between the si-NC group and the co-transfection group(P＜0.01,P＜0.05).Conclusion MiR-508-3p is lowly expressed in EOC cancer tissue,and it may inhibit the migration and invasion of ovarian cancer cells by targeting ZEB1 expression.

Objective·To explore the roles of hyaluronic acid methacryloyl(HAMA)hydrogel in skin wound healing and to characterize the microenvironmental landscape at wound sites.Methods·A full-thickness skin excision model was established in mice,which were randomly divided into a control group(n=3)and a HAMA group(n=3).The wound in the HAMA and control groups were covered with 100 μL of HAMA hydrogel and 100 μL of phenyl-2,4,6-trimethylbenzoylphosphonic acid lithium(LAP),respectively.Both groups were then irradiated with a UV lamp for 20 s.The residual wound areas was measured on days 0,3,7,10,and 14.Wound healing effects of HAMA hydrogel were analyzed by measuring the residual wound area and through H-E staining.Single-cell RNA sequencing technology was utilized to analyze the cellular profile of local wound skin tissues at day 14 post-injury.Immunofluorescence assay was used to detect the levels of type I collagen,type Ⅲ collagen,F4/80,CD206,and CD86 in the wound sites.The mRNA expression levels of Arg1,Nos2,Itgam,and Itgb2 in the mouse macrophage cell line Raw264.7 co-cultured with HAMA hydrogel for 24 h were detected by RT-qPCR.The fibroblasts and macrophages in the local skin of the mouse wound on day 14 were analyzed using the Seurat package,and the communication between fibroblasts and macrophages was analyzed using the CellChat package.Results·Mice treated with HAMA hydrogel exhibited a significantly faster rate of wound healing process compared to the control group.At day 14,wounds in the HAMA-treated mice had already healed,while those in the control group remained unhealed.Single-cell RNA sequencing analysis revealed a remarkable increase in the proportion of fibroblasts in the skin tissues of HAMA-treated wounds.The proportion of the Col3a1-high-expressing fibroblast subset increased(90.2%)compared to the control group(79.8%),while the proportion of the Col1a1-high-expressing fibroblast subset decreased(5.7%vs 15.9%).Immunofluorescence analysis confirmed that the level of type Ⅲ collagen in the wound tissues of the HAMA group was significantly higher than that in the control group(P=0.035),while the level of type Ⅰ collagen was significantly lower(P=0.044).Although there was no significant difference in the proportions of macrophages in the wound tissues between the HAMA-treated and control groups,scRNA sequencing data and in vitro experiments using Raw264.7 cells showed that HAMA hydrogel could induce the expression of Arg1 and decrease the expression of Nos2 in the macrophages(P<0.001).Additionally,macrophages in the HAMA-treated wounds expressed higher levels of CD206 and lower levels of CD86(P=0.042,P=0.011).The results of the CellChat analysis showed that,compared to the control group,increased communication intensity was observed between macrophages and fibroblasts subsets at the wound sites in the mice of HAMA group.Conclusion·The microenvironment after HAMA hydrogel treatment is conducive to skin wound healing,characterized by a local aggregation of anti-inflammatory macrophages and fibroblasts that secrete type Ⅲ collagen.

Objective:The serum ferritin-to-albumin ratio(FAR)has been proposed as a novel prognostic marker for sepsis,but its predictive role in outcomes among critically ill patients remains unclear.This study aimed to investigate the correlation between FAR and in-hospital mortality among critically ill patients.Methods:Based on the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ),8,136 Intensive Care Unit(ICU)patients were included.Multivariate logistic regression was used to evaluate the predictive value of FAR for in-hospital mortality,and receiver operating characteristic(ROC)curve analysis was performed to compare its predictive performance with other parameters.Results:The overall in-hospital mortality was 2.31％.Multivariate logistic regression analysis showed that FAR was an independent predictor of in-hospital death(OR=2.190,95％CI=1.730-2.780,P=0.000).ROC analysis revealed that FAR achieved a significantly higher area under the curve(AUC)value(0.72)compared to ferritin(0.69)and albumin(0.26),with an optimal cutoff value of 80.57.Subgroup analysis demonstrated no significant interaction effects between FAR and most subgroups(P＞0.05),except for the hypertension subgroup.Conclusion:FAR is significantly associated with in-hospital mortality in critically ill patients,and elevated FAR values indicate an increased risk of death.

Ischemic stroke and hemorrhagic stroke have different pathogenic mechanisms,but share similarities in metabolic dysregulation,inflammatory responses and oxidative stress.This paper summarized 28 metabolic markers shared between ischemic stroke and hemorrhagic stroke with consistent trends through literature review.It also provided an overview of their involvement in abnormal energy metabolism,inflammatory responses,blood-brain barrier disruption,and neural damage in relation to stroke.The aim is to provide a scientific basis for future prognosis,curative efficacy evaluation and future homotherapy of ischemic stroke and hemorrhagic stroke,and provide insights for the development of new therapies and new drugs.