Objective:To investigate the therapeutic effects of Akkermansia muciniphila (AKK) on liver injury induced by cholestasis and its mechanisms in regulating bile acid metabolism. Methods:The cholestatic mouse model was established by bile duct ligation (BDL). A total of 35 male C57BL/6J mice (8 weeks old) were divided into 5 groups using a random numder table method (7 mice per group): group A (control group), group B (BDL group), group C (BDL+AKK group), group Z (BDL+AKK+Z/E-guggulsterone group), and group G (BDL+AKK+Gly-β-muricholic acid group). Preoperative and postoperative changes in liver function and bile acid metabolism indicators was observed of mice in groups A, B, and C. The liver function and fibrosis markers were compared between groups, as well as serum, liver, and fecal total bile acid levels, fecal bile acid composition, liver histopathology, and the mRNA expression of key proteins involved in the bile acid enterohepatic circulation and the farnesoid X receptor (FXR) signaling pathway were compared. Multiple groups of data were compared using analysis of variance or nonparametric Kruskal Wallis H test. Results:Twelve days after BDL, in groups A, B, and C, mice in group C exhibited milder postoperative jaundice and their body weights on postoperative days 4-5 and 7-11 were heavier than those in group B mice (all P<0.05). The liver tissues of mice in group C were milder than those in group B in terms of appearance, histopathology, inflammation and liver fibrosis (all P<0.05). The levels of serum alanine aminotransferase, aspartate aminotransferase, as well as the expression levels of liver α-smooth muscle actin and type Ⅰ collagen, and the levels of total liver bile acid and fecal β-murine bile acid in the C group mice were all lower than those of group B mice ((46±20) vs. (90±34) U/L, (96±17) vs.(122±31) U/L, (2.01±0.11)% vs. (7.55±0.21)%, (1.92±0.10)% vs. (7.28±0.51)%, (62±14) vs. (124±39) μmol/mg, 3 052 (1 522, 6 406) vs. 14 756 (6 582, 33 474) ng/g,all P<0.05). And the mRNA expression levels of cholesterol 7α-hydroxylase and bile salt export pump of the ileum, etc. in group C mice were lower than those in group B mice (all P<0.05), while the mRNA expression levels of FXR and fibroblast growth factor 15 in the intestine were higher than those in group B mice (all P<0.05). In groups B, C, Z, and G, compared with group C, mice in groups Z and G had aggravated liver injury and fibrosis, increased total bile acid levels in the liver, and increased serum alanine aminotransferase, total bilirubin, and expression levels of liver α-smooth muscle activator protein and type I collagen (all P<0.05). There was no statistically difference in the above indicators between group Z and group G (all P<0.05). Conclusion:AKK reduces liver bile acid synthesis, regulates bile acid metabolism, alleviate liver function damage and fibrosis, and improves clinical phenotypes by activating the intestinal FXR-fibroblast growth factor 15 signaling pathway.

Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

Objective:To investigate the therapeutic effects of Akkermansia muciniphila (AKK) on liver injury induced by cholestasis and its mechanisms in regulating bile acid metabolism. Methods:The cholestatic mouse model was established by bile duct ligation (BDL). A total of 35 male C57BL/6J mice (8 weeks old) were divided into 5 groups using a random numder table method (7 mice per group): group A (control group), group B (BDL group), group C (BDL+AKK group), group Z (BDL+AKK+Z/E-guggulsterone group), and group G (BDL+AKK+Gly-β-muricholic acid group). Preoperative and postoperative changes in liver function and bile acid metabolism indicators was observed of mice in groups A, B, and C. The liver function and fibrosis markers were compared between groups, as well as serum, liver, and fecal total bile acid levels, fecal bile acid composition, liver histopathology, and the mRNA expression of key proteins involved in the bile acid enterohepatic circulation and the farnesoid X receptor (FXR) signaling pathway were compared. Multiple groups of data were compared using analysis of variance or nonparametric Kruskal Wallis H test. Results:Twelve days after BDL, in groups A, B, and C, mice in group C exhibited milder postoperative jaundice and their body weights on postoperative days 4-5 and 7-11 were heavier than those in group B mice (all P<0.05). The liver tissues of mice in group C were milder than those in group B in terms of appearance, histopathology, inflammation and liver fibrosis (all P<0.05). The levels of serum alanine aminotransferase, aspartate aminotransferase, as well as the expression levels of liver α-smooth muscle actin and type Ⅰ collagen, and the levels of total liver bile acid and fecal β-murine bile acid in the C group mice were all lower than those of group B mice ((46±20) vs. (90±34) U/L, (96±17) vs.(122±31) U/L, (2.01±0.11)% vs. (7.55±0.21)%, (1.92±0.10)% vs. (7.28±0.51)%, (62±14) vs. (124±39) μmol/mg, 3 052 (1 522, 6 406) vs. 14 756 (6 582, 33 474) ng/g,all P<0.05). And the mRNA expression levels of cholesterol 7α-hydroxylase and bile salt export pump of the ileum, etc. in group C mice were lower than those in group B mice (all P<0.05), while the mRNA expression levels of FXR and fibroblast growth factor 15 in the intestine were higher than those in group B mice (all P<0.05). In groups B, C, Z, and G, compared with group C, mice in groups Z and G had aggravated liver injury and fibrosis, increased total bile acid levels in the liver, and increased serum alanine aminotransferase, total bilirubin, and expression levels of liver α-smooth muscle activator protein and type I collagen (all P<0.05). There was no statistically difference in the above indicators between group Z and group G (all P<0.05). Conclusion:AKK reduces liver bile acid synthesis, regulates bile acid metabolism, alleviate liver function damage and fibrosis, and improves clinical phenotypes by activating the intestinal FXR-fibroblast growth factor 15 signaling pathway.

Objective: To examine the characteristics of physical activity among secondary vocational school students and its associations with depressive symptoms, anxiety symptoms, and their co-existence, so as to provide evidence for promoting their mental health. Methods: From September to December 2024, a questionnaire survey was conducted on 5 141 secondary vocational school students using convenience sampling method across 16 secondary vocational schools in 8 provinces/municipalities, including Fujian, Chongqing, Guangdong, Guangxi, Hubei, Jiangxi, Shanghai and Zhejiang. A self designed questionnaire, International Physical Activity Questionnaire Short Form, Patient Health Questionnaire-9 and Generalized Anxiety Disorder Scale-7 were used to assess basic information, physical activity characteristics, and depressive and anxiety symptoms. Chi-square test and Logistic regression model were used to analyze the associations of physical activity characteristics with depressive symptoms, anxiety symptoms, and their co-existence. Results: Among secondary vocational school students, 22.2% had depressive symptoms, 12.2% had anxiety symptoms, and 10.5% had both conditions. After adjustment for confounding factors such as sex, grade, and family structure, Logistic regression analyses showed that a high physical activity level, meeting the recommendation for daily moderate to vigorous physical activity (MVPA), and a concentrated physical activity pattern were associated with lower odds of depressive symptoms, anxiety symptoms, and their co-existence ( OR =0.70-0.81, all P <0.05). Regular weekly MVPA and a regular physical activity pattern were associated only with lower odds of depressive symptoms ( OR =0.79, 0.70, both P <0.05). Sex stratified analyses showed that meeting the recommendation for daily MVPA and a concentrated physical activity pattern were associated with lower odds of depressive symptoms, anxiety symptoms, and their co-existence among boys ( OR =0.60-0.71); a high physical activity level, regular weekly MVPA, and a regular physical activity pattern were associated with lower odds of depressive symptoms among boys ( OR =0.65-0.78)(all P <0.05). Meanwhile, a high physical activity level, meeting the recommendation for daily MVPA, regular weekly MVPA, and regular and concentrated physical activity patterns were associated with lower odds of depressive symptoms in female students ( OR =0.72-0.79) (all P <0.05). Conclusions Physical activity characteristics are associated with depressive symptoms, anxiety symptoms, and their co-existence among secondary vocational school students. Schools should optimize physical activity promotion strategies according to sex specific characteristics to reduce the occurrence of depressive and anxiety symptoms among secondary vocational school students.

Objective: To analyze the compliance status of physical fitness indicator and lifestyle characteristics among secondary vocational school students, as well as their associations, so as to provide a reference for physical fitness promotion among secondary vocational school students. Methods: Using a convenience sampling method, a questionnaire survey and physical fitness tests were conducted from September to December 2024 among 5 141 secondary vocational school students recruited from 16 secondary vocational schools across 8 provinces/municipalities in China, including Fujian, Chongqing, Guangdong, Guangxi, Hubei, Jiangxi, Shanghai and Zhejiang. Data on lifestyle factors were collected using a self designed questionnaire combined with standardized scales, including dietary habits, unhealthy behaviors, and 24 hour behaviors (physical activity, screen time, and sleep behavior). Multivariable Logistic regression model was used to analyze the associations of individual lifestyle behaviors and clustering of unhealthy lifestyle behaviors with non-compliance in physical fitness indicators among secondary vocational school students. Results: The compliance rates for waist circumference, vital capacity, grip strength, standing long jump, 30 second sit ups, 20 meter shuttle run, 50 meter dash, sit and reach, 20 second side steps among secondary vocational school students were 55.9%, 89.6%, 81.8%, 79.4%, 77.8%, 61.4%, 87.0%, 12.6%, and 63.5%, respectively, with a non-overweight/obesity rate of 78.9%. The reporting rates of daily breakfast consumption, milk consumption, and vegetable consumption were 58.9%, 18.3%, and 37.5%, respectively. The reporting rates of frequent takeout consumption, frequent sugar sweetened beverage consumption, smoking, alcohol drinking, insufficient moderate to vigorous physical activity (MVPA), excessive screen time, and insufficient sleep were 30.0%, 43.8%, 8.4%, 15.8%, 42.9%, 90.8%, and 42.6%, respectively. Multivariable Logistic regression analysis showed that secondary vocational school students with insufficient MVPA had higher risks of non-compliance in vital capacity, grip strength, standing long jump, 30 second sit ups, 20 meter shuttle run, 50 meter dash, and 20 second side steps ( OR =1.22- 1.60 ); secondary vocational school students who consumed breakfast daily had lower risks of non-compliance in vital capacity and overweight/obesity ( OR =0.81, 0.85); daily vegetable consumption was associated with a lower risk of vital capacity non-compliance ( OR =0.72); frequent takeout consumption was associated with an increased risk of non-compliance in the sit and reach test ( OR =1.28); smoking was associated with increased risks of non-compliance in the 20 meter shuttle run and 20 second side steps ( OR =1.38, 1.58) (all P <0.05). Regarding the clustering of unhealthy behaviors, secondary vocational school students with 4- 5 clustered unhealthy behaviors had higher risks of non-compliance in waist circumference and standing long jump; those with≥6 clustered behaviors had higher risks of non-compliance in standing long jump, 20 meter shuttle run, and 20 second side step ( OR = 1.17-1.36, all P <0.05). Conclusions The clustering of unhealthy behaviors is negatively associated with physical fitness status among secondary vocational school students. Secondary vocational schools should prioritize the promotion of comprehensive lifestyle management to improve the physical fitness levels of secondary vocational school students.

To explore the in vitro and in vivo synergistic effect of paclitaxel in combination with co-listin against MDREscherichia coli(E.coli)and the corresponding mechanism of synergism,we measured the MICs of PTX alone and combination of PTX+antimicrobial drugs on E.coli and Staphylococcus aureus(S.aureus)by broth microdilution method.Then,checkerboard method was used to determine the FICI of PTX+COL combination,and the antibacterial synergies of PTX and COL was further explored through analyzing the membrane permeability and efflux pump ac-tivity.The MICs results showed that the MIC values of PTX alone against E.coli(G5,E25)and S.aureus S238 were＞1 024 mg/L and 512 mg/L,respectively.Meanwhile,we found that the anti-bacterial activity of COL against E.coli could be significantly enhanced(MIC decreased by 4 to 8 times)when used in combination with PTX.The checkerboard test showed that the FICI values of PTX combined with COL for E.coli(G5,E25)were 0.31 and 0.29,respectively,indicating a synergistic antibacterial effect on these strains.The FICI values of PTX combined with COL for E.coli G21,S.aureus(S237 and S238)were 0.51,0.75 and 0.53,respectively,indicating additive effects on these strains.In the mouse abdominal infection model,the combination group could ex-tremely significantly reduce the bacterial burden of E.coli in abdominal compared to the COL or PTX alone group(P＜0.001).The analysis of membrane permeability and efflux pump activity showed that PTX combined with COL significantly increased the inner and outer membrane per-meability of E.coli(G5 and E25),and markedly inhibited the efflux pumping activity of E.coli,when compared that of PTX and COL alone(P＜0.01).The above results indicated that the com-bination of PTX and COL could exert a synergistic in vivo and in vitro antibacterial effect on COL-resistant E.coli through increasing bacterial membrane permeability and inhibiting efflux pump activity.This study provides the theoretical foundation for the development of a novel combi-nation regimen for the treatment of MDR E.coli infection.

Objective To investigate the distribution and antimicrobial resistance profiles of clinical isolates in Xi'an No.3 Hospital from 2019 to 2023.Methods Clinical isolates were collected from January 1,2019 to December 31,2023.Antimicrobial susceptibility testing was carried out according to a unified protocol of China Antimicrobial Resistance Surveillance Network using Kirby-Bauer method or automated systems.The data were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2023.Results A total of 6 621 clinical isolates were collected from 2019 to 2023,including 1 569(23.7％)strains of Gram-positive bacteria and 5 052(76.3％)strains of Gram-negative bacteria.The prevalence of methicillin-resistant S.aureus,S.epidermidis and other Staphylococcus species(except SS.pseudintermedius and S.schleiferi)was 39.0％,62.3％,and 74.4％,respectively.Methicillin-resistant strains showed much higher resistance rates to most of other antimicrobial agents than methicillin-sensitive strains.No Staphylococcus strains were found resistant to vancomycin or linezolid.E.faecium strains demonstrated much higher resistance rates to most antimicrobial agents tested than E.faecalis.The prevalence of linezolid-resistant E.faecalis and vancomycin-resistant E.faecium was 0.9％and 0.4％,respectively.The prevalence of penicillin-nonsusceptible strains(PISP+PRSP)was 5.8％in nonmeningitis S.pneumoniae isolates.The prevalence of ESBL-producing E.coli,K.pneumoniae,and P.mirabilis in Enterobacterales was 48.5％,37.8％,and 47.2％,respectively.Among Enterobacterales strains,K.pneumoniae had the highest resistance rate to imipenem(18.2％)and meropenem(17.9％).Other Enterobacterales were highly sensitive to carbapenems.The resistance rates of P.aeruginosa to imipenem and meropenem were 22.5％and 19.5％,respectively.The resistance rates of A.baumannii to imipenem and meropenem were 65.0％and 71.6％,respectively.Conclusions Antibiotic resistance is still serious in this hospital.Nearly half of the strains of E.coli,K.pneumoniae and P.mirabilis produced ESBLs.K.pneumoniae and A.baumannii showed high resistance rates to carbapenems.Antimicrobial resistance surveillance should be performed appropriately.Relevant departments need to strengthen cooperation to curb the spread of drug-resistant bacteria.

Objective To investigate the distribution and antimicrobial resistance profiles of clinical isolates in Xi'an No.3 Hospital from 2019 to 2023.Methods Clinical isolates were collected from January 1,2019 to December 31,2023.Antimicrobial susceptibility testing was carried out according to a unified protocol of China Antimicrobial Resistance Surveillance Network using Kirby-Bauer method or automated systems.The data were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2023.Results A total of 6 621 clinical isolates were collected from 2019 to 2023,including 1 569(23.7％)strains of Gram-positive bacteria and 5 052(76.3％)strains of Gram-negative bacteria.The prevalence of methicillin-resistant S.aureus,S.epidermidis and other Staphylococcus species(except SS.pseudintermedius and S.schleiferi)was 39.0％,62.3％,and 74.4％,respectively.Methicillin-resistant strains showed much higher resistance rates to most of other antimicrobial agents than methicillin-sensitive strains.No Staphylococcus strains were found resistant to vancomycin or linezolid.E.faecium strains demonstrated much higher resistance rates to most antimicrobial agents tested than E.faecalis.The prevalence of linezolid-resistant E.faecalis and vancomycin-resistant E.faecium was 0.9％and 0.4％,respectively.The prevalence of penicillin-nonsusceptible strains(PISP+PRSP)was 5.8％in nonmeningitis S.pneumoniae isolates.The prevalence of ESBL-producing E.coli,K.pneumoniae,and P.mirabilis in Enterobacterales was 48.5％,37.8％,and 47.2％,respectively.Among Enterobacterales strains,K.pneumoniae had the highest resistance rate to imipenem(18.2％)and meropenem(17.9％).Other Enterobacterales were highly sensitive to carbapenems.The resistance rates of P.aeruginosa to imipenem and meropenem were 22.5％and 19.5％,respectively.The resistance rates of A.baumannii to imipenem and meropenem were 65.0％and 71.6％,respectively.Conclusions Antibiotic resistance is still serious in this hospital.Nearly half of the strains of E.coli,K.pneumoniae and P.mirabilis produced ESBLs.K.pneumoniae and A.baumannii showed high resistance rates to carbapenems.Antimicrobial resistance surveillance should be performed appropriately.Relevant departments need to strengthen cooperation to curb the spread of drug-resistant bacteria.

Objective To assess and compare the passing rates of 3 radiotherapy dosimetric verification systems,namely Portal Dosimetry(PD),SunCheck(SNC),and ArcCheck(ARC)for different gamma criteria,and to analyze their performance across different irradiation sites.Methods A retrospective analysis was conducted on 185 radiotherapy plans,including those for head and neck,chest,and pelvic regions.The passing rates of 3 systems for different gamma criteria(3%/2 mm,3%/1 mm,2%/2 mm,and 2%/1 mm)were collected and compared across different sites.Results For the 3%/2 mm criterion,PD system had the highest passing rate across all evaluation standards,especially for the 2%/1 mm criterion,where it significantly outperformed both ARC and SNC systems.The high-resolution imaging capability of PD system enabled it to deliver exceptional performance in complex treatment plans,particularly for chest and pelvic tumors.ARC system performed well at looser criteria but showed a significant drop in passing rates with stricter gamma criteria,particularly in head and neck and complex anatomical regions.SNC system demonstrated intermediate performance,surpassing ARC under stricter criteria,while its automation and efficient processing capabilities offered a distinct advantage in high-volume clinical environments.Conclusion All 3 verification systems meet the fundamental requirements for clinical radiotherapy plan verification.However,their performance varies depending on the gamma criteria.It is recommended to select the appropriate verification system based on the complexity of the treatment plan,irradiation site,and gamma criteria.PD system is best suited for high-precision treatment areas(e.g.,chest and pelvis),whereas ARC and SNC are more suitable for routine and moderately complex treatment plans.

Objective To assess and compare the passing rates of 3 radiotherapy dosimetric verification systems,namely Portal Dosimetry(PD),SunCheck(SNC),and ArcCheck(ARC)for different gamma criteria,and to analyze their performance across different irradiation sites.Methods A retrospective analysis was conducted on 185 radiotherapy plans,including those for head and neck,chest,and pelvic regions.The passing rates of 3 systems for different gamma criteria(3%/2 mm,3%/1 mm,2%/2 mm,and 2%/1 mm)were collected and compared across different sites.Results For the 3%/2 mm criterion,PD system had the highest passing rate across all evaluation standards,especially for the 2%/1 mm criterion,where it significantly outperformed both ARC and SNC systems.The high-resolution imaging capability of PD system enabled it to deliver exceptional performance in complex treatment plans,particularly for chest and pelvic tumors.ARC system performed well at looser criteria but showed a significant drop in passing rates with stricter gamma criteria,particularly in head and neck and complex anatomical regions.SNC system demonstrated intermediate performance,surpassing ARC under stricter criteria,while its automation and efficient processing capabilities offered a distinct advantage in high-volume clinical environments.Conclusion All 3 verification systems meet the fundamental requirements for clinical radiotherapy plan verification.However,their performance varies depending on the gamma criteria.It is recommended to select the appropriate verification system based on the complexity of the treatment plan,irradiation site,and gamma criteria.PD system is best suited for high-precision treatment areas(e.g.,chest and pelvis),whereas ARC and SNC are more suitable for routine and moderately complex treatment plans.