ObjectiveThis study aims to explore the mechanism by which Yishen Huoxue Tongqiao Formula improves metabolism-neuroplasticity and treats unilateral vestibular labyrinth destruction by regulating the metabolic balance of glutamate （Glu）/γ-aminobutyric acid （GABA）. Methods48 Sprague-Dawley （SD） adult rats were randomly divided into the sham operation group， model group， Yishen Huoxue Tongqiao Formula groups with low， medium， and high doses （9.20， 18.39， 36.78 g·kg^-1）， and betahistine group （1.62 mg·kg^-1）. A unilateral vestibular labyrinth destruction （vestibular dysfunction） model was established by intratympanic injection of chloroform into the right ear， while the control group received intratympanic injection of normal saline. Drugs were administered once daily for seven consecutive days. During the period， behavioral tests were performed to evaluate the behaviors of rats after unilateral vestibular labyrinth destruction. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe the neuronal morphology in the medial vestibular nucleus. Golgi staining was employed to assess the number of dendritic spines of neurons in the medial vestibular nucleus. Ultra-performance liquid chromatography-tandem mass spectrometry （LC-ESI-MS/MS） was utilized to detect Glu/GABA. Immunofluorescence and immunohistochemistry were used to detect the expressions of neuronal nuclei （NeuN）， growth-associated protein 43 （GAP-43）， and glial fibrillary acidic protein （GFAP）. Western blot and real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） were applied to determine the expressions of glutamate-immunoreactive （Glu-IR）， GABA， GFAP， postsynaptic density protein 95 （PSD-95）， and GAP-43. ResultsCompared with the sham operation group， the model group presented with head deviation， balance disorder， increased tail suspension score， nuclear consolidation of medial vestibular nerve neurons， and decreased Nissl bodies （P<0.01）. The number of dendritic spines in neurons and NeuN-positive cells decreased. The content of Glu decreased. The content of GABA increased （Glu/GABA decreased）. The expression of GAP-43 was down-regulated， and GFAP was up-regulated （P<0.05， P<0.01）. The expressions of Glu-IR， PSD-95， and GAP-43 proteins， as well as Glu-IR mRNA decreased， while the expressions of GABA and GFAP proteins and mRNA increased （P<0.05， P<0.01）. Compared with those in the model group， the head deviation， imbalanced behavior， and tail suspension scores in each treatment group decreased， with alleviated neuronal injury and recovered Nissl bodies （P<0.01）. The number of dendritic spines of neurons increased， and the number of NeuN-positive cells rebounded. The content of Glu increased， and the content of GABA decreased （Glu/GABA increased）. GFAP was down-regulated， and GAP-43 was up-regulated （P<0.05， P<0.01）. The expressions of Glu-IR， PMD-95， and GAP-43 proteins， as well as Glu-IR mRNA increased， while the expressions of GABA and GFAP proteins and mRNA decreased. The effect was more significant in the high-dose group （P<0.01）. ConclusionThe Yishen Huoxue Tongqiao Formula can alleviate vestibular dysfunction， and its mechanism may be associated with regulating the metabolic balance of Glu/GABA， mitigating neural damage， improving synaptic plasticity （promoting GAP-43 expression and inhibiting GFAP expression）， and facilitating vestibular compensation.

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.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.

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 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 explore the gender differences and the influence of varus and valgus deformities on distal femur rotational alignment in patients with knee osteoarthritis so as to provide reference for the distal femur rotational osteotomy in total knee arthroplasty(TKA).Methods CT data of 125 knees with osteoarthritis suitable for TKA(including 56 males and 69 females;78 varus knees and 47 valgus knees)were collected and received three-dimensional imaging reconstruction with Mimics software.We measured the posterior condylar angle(PCA),the angle between the anteroposterior axis and the surgical epicondylar axis(ASA),and the angle between the anteroposterior axis and the posterior condylar axis(APA).We also compared gender differences and the influences of varus-valgus deformities on distal femur rotational alignments.Results The PCA and ASA values of distal femur rotational alignments were(3.5±1.1)° vs.(2.8±1.2)°(P=0.001)and(90.6±3.4)° vs.(91.9±3.5)°(P=0.028)for males and females,with statistically differences between the genders.There was no statistically difference in APA between males and females(P=0.482).The PCA values of distal femur rotational alignment in varus and valgus knees were(3.6±1.1)° and(2.9±1.2)°,with a statistically difference between the two groups(P=0.001).There were no statistically differences in ASA or APA between varus and valgus knees(P＞0.05).Conclusion Gender and varus-valgus deformities of knee joint affect the distal femur rotational alignment.Distal femur rotational osteotomy angle should be determined according to the patient's CT imaging before TKA to reduce the errors caused by individual differences and improve the accuracy of the distal femur rotational alignment during TKA.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To investigate the predictive value of color Doppler ultrasound combined with electrocardio-gram for right heart dys function in patients with pulmonary heart disease(PHD).Methods:A total of 100 PHD patients admitted in Dongcheng Branch of First Affiliated Hospital of Anhui Medical University between January 2020 and December 2023 were retrospectively analyzed.According to results of 6min walking test(6MWT),pa-tients were divided into good right heart function group(n=64,≥350m)and right heart dysfunction group(n=36,＜350m).The indexes of cardiac color ultrasound[isovolumic relaxation time(IVRT),isovolumetric contraction time(IVCT)and right ventricular Tei index],ECG[24h mean R-R interval standard deviation(SDNN),normal R-R interval standard deviation per 5min(SDANN)and the ratio of low frequency components to high frequency components(LF/HF)]were compared between two groups.Receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of color Doppler ultrasound,ECG and their combination for right heart dys-function in PHD patients.Spearman correlation coefficient was used to analyze the association of color Doppler ul-trasound,ECG and their combination with right heart dysfunction in PHD patients.Results:Compared with those in good right heart function group,patients in right heart dysfunction group had significant higher IVRT[(120.64±14.08)ms vs.(97.87±10.93)ms],IVCT[(84.28±12.33)ms vs.(71.92±10.61)ms]and Tei index[(0.85±0.11)vs.(0.63±0.07)](P＜0.001 all),and significant lower SDNN[(75.52±12.58)ms vs.(85.58±11.75)ms],SDANN[(63.86±10.92)ms vs.(76.75±11.71)ms]and LF/HF[(1.33±0.19)vs.(1.84±0.27)](P＜0.001 all).ROC curve indicated that the AUC of color Doppler ultrasound combined ECG in diagnosing right heart dysfunction in PHD patients was 0.911(95％CI 0.838～0.959),which was significantly higher than those of color Doppler ultrasound[0.775(95％CI 0.681～0.853),Z=2.404,P=0.016]and ECG[0.688(95％CI 0.588～0.777),Z=3.968,P=0.001]alone.Spearman correlation analysis indicated that there was a significant positive correlation of color Doppler ultrasound(r=0.547),ECG(r=0.375)and their combination(r=0.810)with right heart dysfunction in PHD patients(P＜0.001 all),and the correlation between combined detection and right heart dysfunction in PHD patients was significantly higher.Conclusion:Color Doppler ultrasound combined with ECG possesses high diagnostic performance for right heart dysfunction in PHD patients.

Objective To explore the value of magnetic resonance imaging(MRI)T2-weighted imaging(T2WI)and diffusion-weighted imaging(DWI)sequences in evaluating the therapeutic effect of neoadjuvant chemoradiotherapy(nCRT)for advanced rectal cancer.Methods A retrospective analysis was conducted on 124 patients with advanced rectal cancer who received nCRT from November 2020 to November 2023 in Dazhou Integrated TCM&Western Medicine Hospital.All patients underwent radical resection of rectal cancer at 6-8 weeks after the end of nCRT.MRI scans were performed before nCRT and at 6-8 weeks after the end of nCRT.The differences in tumor long and short diameters,signal intensity in tumor(SIT),apparent diffusion coefficient(ADC)and other parameters were measured,and the MRI tumor regression grade was analyzed.Surgery was performed at 3 days after the second examination.The patients were divided into grade 0-1 group and grade 2-3 group according to the postoperative pathological tumor regression grade.The differences of MRI parameters before and after treatment were compared between groups.The consistency of T2WI sequence and DWI sequence in the diagnosis of tumor regression grade after nCRT was analyzed.ROC curve was used to analyze the value of MRI parameters in evaluating the therapeutic effect of nCRT.Results The differences of tumor long diameter,short diameter,SIT and ADC measured by twice MRI examination in grade 0-1 group were increased as compared with grade 2-3 group(P<0.05).MRI detected MRI tumor regression grade 1 in 28 cases(22.58%),grade 2 in 30 cases(24.19%),grade 3 in 31 cases(25.00%),grade 4 in 25 cases(20.16%)and grade 5 in 10 cases(8.06%).Consistency analysis showed that MRI had a sensitivity,specificity,accuracy rate and Kappa value of 92.45%,87.32%,89.51%and 0.788 in evaluating postoperative tumor regression grade.ROC analysis revealed that the AUC of MRI parameters such as differences in tumor long diameter,short diameter,SIT and ADC measured by twice MRI examinations in evaluating the nCRT efficacy ranged from 0.827 to 0.921,and the AUC of combined evaluation was 0.928(P<0.05).Conclusion The combined evaluation of MRI T2WI and DWI sequences can be served as an effective tool for evaluating the therapeutic effect of nCRT for advanced rectal cancer.

BACKGROUND: Diabetes mellitus with nonalcoholic fatty liver disease (DM-NAFLD) represents a complex metabolic syndrome with significant clinical challenges. This study explores the therapeutic potential and underlying mechanisms of umbilical cord-derived mesenchymal stem cells (UCMSCs)-derived extracellular vesicles (EVs) in DM-NAFLD. METHODS: UCMSCs-EVs were isolated and characterized. DM-NAFLD mouse model was developed through highenergy diet and streptozotocin injection. Additionally, primary mouse hepatocytes were exposed to high glucose to simulate cellular conditions. Hepatic tissue damage, body weight changes, lipid levels, glucose and insulin homeostasis, and hepatic lipid accumulation were evaluated. The interaction between UCMSCs-EVs and hepatocytes was assessed, focusing on the localization and function of circ-Tulp4. The study also investigated the expression of circularRNA TUBlike protein 4 (circ-Tulp4), heterogeneous nuclear ribonucleoprotein C (HNRNPC), abhydrolase domain containing 6 (ABHD6), cleaved Caspase-1, NLR family pyrin domain containing 3 (NLRP3) and cleaved N-terminal gasdermin D (GSDMD-N). The binding of circ-Tulp4 to lysine demethylase 6B (KDM6B) and the subsequent epigenetic regulation of ABHD6 by H3K27me3 were analyzed. RESULTS: Circ-Tulp4 was reduced, while HNRNPC and ABHD6 were elevated in DM-NAFLD models. UCMSCs-EVs attenuated hepatic steatosis and inhibited the NLRP3/cleaved Caspase-1/GSDMD-N pathway. EVs delivered circ-Tulp4 into hepatocytes, thereby restoring circ-Tulp4 expression. Elevated circ-Tulp4 enhanced the recruitment of H3K27me3 to the HNRNPC promoter through interaction with KDM6B, thus suppressing HNRNPC and ABHD6. Overexpression of HNRNPC or ABHD6 counteracted the protective effects of UCMSCs-EVs, exacerbating pyroptosis and hepatic steatosis in DM-NAFLD. CONCLUSION UCMSCs-EVs deliver circ-Tulp4 into hepatocytes, where circ-Tulp4 inhibits the HNRNPC/ABHD6 axis, thereby reducing pyroptosis and alleviating DM-NAFLD. These findings provide a novel therapeutic avenue for targeting DM-NAFLD through modulation of cell pyroptosis.