AIM:To observe the role of enoyl-coenzyme A hydratase/L-3-hydroxyacyl-coenzyme A dehydroge-nase(Ehhadh)in renal tubulointerstitial inflammation in high-fat diet(HFD)fed mice,and to explore its molecular mecha-nism.METHODS:Twenty-four C57BL/6N mice were randomly divided into 4 groups:standard diet(SD)group,HFD group,HFD with Ehhadh overexpression(HFD+Ehh)group and HFD with blank vector(HFD+Vec)group.Each group consisted of 6 mice.The HFD mice were fed with a diet containing 60%fat,20%protein,and 20%carbohydrates for 16 weeks.Briefly,at the end of 8 weeks,the mice in HFD+Ehh or HFD+Vec group were injected with adeno-associated virus 9(AAV9)-Ehhadh or AAV9-vector via the tail vein,and then continued another 8-week HFD feeding.At the end of the experiments,the renal function and morphological changes were observed.The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1 p10,interleukin-1β(IL-1β)and IL-18 in the kidney were detected by Western blot and immunohistochemistry.Immunofluorescence staining was used to detect the colocalization of Ehhadh and peroxisomal biogenesis factor 14(Pex14).ELISA was used to detect the content of IL-1β and IL-18 in the urine.Lipid droplet formation in renal tissues was detected by Nile red staining.Absolute quantitative lip-idomic analysis were used to detect the differential lipid species in renal cortices of the mice in SD,HFD and HFD+Ehh groups.RESULTS:Compared with SD group,the expression of Ehhadh protein was significantly decreased in the peroxi-some of renal tubular epithelium cells in HFD-fed mice(P<0.01).Overexpression of Ehhadh significantly improved renal function(P<0.01)and alleviated the morphological changes of renal tubular epithelial cells in HFD group.Moreover,it significantly inhibited the expression of inflammatory cytokines IL-1β and IL-18 and macrophage infiltration in renal tu-bule interstitium of HFD-fed mice(P<0.01).At the same time,Ehhadh overexpression inhibited HFD-induced NLRP3 inflammasome activation(P<0.01).It also attenuated lipid deposition in renal tubular epithelium cells(P<0.01)and promoted the β-oxidation of long-chain fatty acid such as cholesterol and phospholipids in peroxisomes.CONCLUSION:The Ehhadh inhibits tubulointerstitial inflammation by promoting long-chain fatty acid β-oxidation in peroxisomes and in-hibiting the activation of NLRP3 inflammasome in HFD-fed mice.

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 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.

AIM:To observe the role of enoyl-coenzyme A hydratase/L-3-hydroxyacyl-coenzyme A dehydroge-nase(Ehhadh)in renal tubulointerstitial inflammation in high-fat diet(HFD)fed mice,and to explore its molecular mecha-nism.METHODS:Twenty-four C57BL/6N mice were randomly divided into 4 groups:standard diet(SD)group,HFD group,HFD with Ehhadh overexpression(HFD+Ehh)group and HFD with blank vector(HFD+Vec)group.Each group consisted of 6 mice.The HFD mice were fed with a diet containing 60%fat,20%protein,and 20%carbohydrates for 16 weeks.Briefly,at the end of 8 weeks,the mice in HFD+Ehh or HFD+Vec group were injected with adeno-associated virus 9(AAV9)-Ehhadh or AAV9-vector via the tail vein,and then continued another 8-week HFD feeding.At the end of the experiments,the renal function and morphological changes were observed.The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1 p10,interleukin-1β(IL-1β)and IL-18 in the kidney were detected by Western blot and immunohistochemistry.Immunofluorescence staining was used to detect the colocalization of Ehhadh and peroxisomal biogenesis factor 14(Pex14).ELISA was used to detect the content of IL-1β and IL-18 in the urine.Lipid droplet formation in renal tissues was detected by Nile red staining.Absolute quantitative lip-idomic analysis were used to detect the differential lipid species in renal cortices of the mice in SD,HFD and HFD+Ehh groups.RESULTS:Compared with SD group,the expression of Ehhadh protein was significantly decreased in the peroxi-some of renal tubular epithelium cells in HFD-fed mice(P<0.01).Overexpression of Ehhadh significantly improved renal function(P<0.01)and alleviated the morphological changes of renal tubular epithelial cells in HFD group.Moreover,it significantly inhibited the expression of inflammatory cytokines IL-1β and IL-18 and macrophage infiltration in renal tu-bule interstitium of HFD-fed mice(P<0.01).At the same time,Ehhadh overexpression inhibited HFD-induced NLRP3 inflammasome activation(P<0.01).It also attenuated lipid deposition in renal tubular epithelium cells(P<0.01)and promoted the β-oxidation of long-chain fatty acid such as cholesterol and phospholipids in peroxisomes.CONCLUSION:The Ehhadh inhibits tubulointerstitial inflammation by promoting long-chain fatty acid β-oxidation in peroxisomes and in-hibiting the activation of NLRP3 inflammasome in HFD-fed mice.

Objective:To explore the association between A Body Shape Index (ABSI) and sarcopenia in Chinese older adults.Methods:Totally 1 728 participants in waves 1 and 3 of the China Health and Retirement Longitudinal Survey (CHARLS) were enrolled in this cohort-based cross-sectional analysis. ABSI was calculated by using anthropometric measurements from CHARLS. According to the Asian Working Group for Sarcopenia (AWGS) 2019 consensus update on sarcopenia, low muscle strength and low muscle mass were used as the diagnostic criteria for sarcopenia. Logistic regression and restricted cubic spline (RCS) were used to assess the relationship between ABSI and sarcopenia, and subgroup and interaction analyses were conducted to evaluate the influence of other factors on this association.Results:High ABSI showed a significant association with the risk of sarcopenia among older adults in China, and RCS analysis demonstrated a positive linear correlation between ABSI and sarcopenia. Additionally, the relationship of ABSI with sarcopenia was significantly modified by educational level and depressive status.Conclusion:ABSI, a novel anthropometric measure, serves as an effective threshold for assessing sarcopenia risk in the Chinese older population, providing a basis for developing clinical interventions and public health strategies for the prevention and early identification of sarcopenia.

Objective To explore the characteristics of the cross-sectional area(CSA)of the vagus nerve in a healthy population in Qujing,Yunnan,and its correlation with demographic characteristics.Methods High-resolution nerve ultrasound examinations were conducted on the vagus nerve of 201 healthy volunteers from a hospital in Qujing,Yunnan from September 2022 to March 2023.The CSA was measured through transverse scans of the vagus nerve.The correlation of vagus nerve CSA with age,body mass index(BMI),and gender was assessed.Results The mean CSA of the bilateral VN were 1.9 mm2(right)and 1.3 mm2(left),respectively.The average CSA of the right vagus nerve was significantly greater than that of the left(P<0.001).In the high-age group(>50 years),the average CSA of the right vagus nerve was significantly higher than that of the low-age group(≤50 years)(P=0.0142).However,there was no statistically significant difference in the average CSA of the right vagus nerve between the BMI>24 kg/m2 group and the≤24 kg/m2 group(P=0.0852).The average CSA of the left vagus nerve showed no statistically significant differences across different age groups and BMI groups(P>0.05),but the average CSA of the bilateral vagus nerve in the male group was greater than that in the female group,with a statistically significant difference(P<0.05).Correlation analysis further confirmed a negative correlation between the average CSA of the right vagus nerve and age(r=-0.17,P=0.0139).Multiple linear regression models indicated that age(P=0.007)and gender(P=0.001)were independent influencing factors for the average CSA of the right vagus nerve.Conclusion In the healthy population of Qujing,Yunnan,the CSA of the right vagus nerve is significantly greater than that of the left,and males also exhibit a significantly greater CSA than females.With increasing age,the vagus nerve gradually becomes thinner.

Objective:To investigate the impact of the number of cesarean deliveries on adverse maternal and neonatal outcomes.Methods:A retrospective analysis was conducted on 11 904 singleton pregnant women who underwent cesarean delivery at the Third Affiliated Hospital of Guangzhou Medical University from January 1st, 2019 to December 31st, 2023. The women were grouped according to the number of cesarean deliveries: those undergoing their first cesarean delivery (1CD group, 7 231 cases), those undergoing their second cesarean delivery (2CD group, 3 749 cases), those undergoing their third cesarean delivery (3CD group, 841 cases), and those undergoing their fourth or more cesarean deliveries (4CD group, 83 cases). Differences in clinical characteristics, related surgical procedures, and adverse maternal and neonatal outcomes among the groups were compared. Binary logistic regression analysis was used to assess the impact of the number of cesarean deliveries on related surgical procedures and adverse maternal and neonatal outcomes.Results:(1) During the 5-year period, the total number of women undergoing cesarean delivery in our hospital showed a slight downward trend, while the proportion of women undergoing three or more cesarean deliveries increased. (2) Compared with women undergoing their first cesarean delivery, women in each repeat cesarean delivery group were older, had higher proportions of advanced maternal age and pre-pregnancy body mass index, and had more pregnancies, deliveries, and induced abortions; the incidence of placenta previa, placental implantation, antepartum hemorrhage, gestational hyperglycemia, and failed trial of labor requiring conversion to surgery was higher, while the incidence of premature rupture of membranes was lower; the proportions of ureteral stent placement, adhesiolysis of the pelvic and abdominal cavities, uterine rupture, uterine reconstruction, uterine artery ligation, hysterectomy, postpartum hemorrhage, and postoperative intestinal obstruction were higher, and the amount of postpartum hemorrhage was greater; the gestational age at delivery of neonates was earlier, but the rates of preterm birth at 28-31 +6 and 32-33 +6 weeks of gestation were lower; the differences were statistically significant ( P<0.05) for all comparisons. (3) The number of cesarean deliveries was not an independent risk factor for the dose-dependent occurrence of placenta previa (a OR=0.99, 95% CI: 0.98-1.01; P=0.261). In women without placenta previa, the number of cesarean deliveries was not a risk factor for placental implantation (a OR=1.12, 95% CI: 0.90-1.39; P=0.320). However, in women with placenta previa, the number of cesarean deliveries was a risk factor for placental implantation (a OR=4.01, 95% CI: 3.08-5.22; P<0.001). In the overall population, the number of cesarean deliveries was a risk factor for ureteral stent placement, adhesiolysis of the pelvic and abdominal cavities, bladder rupture repair, uterine rupture, uterine reconstruction, uterine artery ligation, hysterectomy, postpartum hemorrhage, and preterm birth (all P<0.05). However, the number of cesarean deliveries was not a risk factor for postoperative intestinal obstruction, admission to the intensive care unit, neonatal asphyxia, admission to the neonatal intensive care unit, or neonatal death (all P<0.05). Conclusions:The number of cesarean deliveries could lead to adverse maternal and neonatal outcomes, but the relationship is not simply dose-dependent. It is speculated that the occurrence of severe adverse maternal and neonatal outcomes is more closely related to maternal complications and comorbidities, as well as whether multidisciplinary comprehensive management was received.

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.

To investigate the molecular mechanisms underlying the mechanosensitive ion channel PI-EZO2 in osteoarthritis(OA),we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line.By map-ping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA,we employed the CRISPR/Cas9 synergistic activation mediator(SAM)system to precisely integrate transcriptional ac-tivation elements into the PIEZO2 promoter region.Lentiviral-mediated targeted genomic integration en-sured endogenous PIEZO2 overexpression,confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting,which revealed membrane-specific localization of PIEZO2 protein(localization effi-ciency:78.49％).Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA,while Western blotting validated enhanced membrane-localized protein expression.Strikingly,PIEZO2-overex-pressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls:typeⅡ collagen mRNA expression decreased to 50％of baseline levels,whereas matrix metalloproteinase 13(MMP13)mRNA surged by 20-fold.These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress(10％strain,0.5 Hz,8 h/day for 2 consecutive days).Collectively,we successfully generated a human chondrocyte model with stable PIEZO2 overexpression,which faithfully mirrors mechanotransduction-driven OA progression.This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosig-naling networks and advancing targeted therapeutic discovery.