AIM:To investigate the effects of total flavonoids of Pterocarya hupehensis Skan(PHSTF)on dex-tran sulfate sodium(DSS)-induced ulcerative colitis(UC)mouse model and lipopolysaccharide(LPS)-stimulated RAW264.7 macrophages.METHODS:Thirty-six male C57BL/6J mice(6 to 8 weeks old,SPF grade)were randomly di-vided into 6 groups:negative control(NC)group,3%DSS-induced model group,mesalazine(300 mg·kg-1·d-1)group,and low-dose(62.5 mg·kg-1·d-1),medium-dose(125 mg·kg-1·d-1)and high-dose(250 mg·kg-1·d-1)PHSTF treatment groups,with 6 mice in each group.The mice in NC group received distilled water,while those in other groups were treated with a 3%DSS solution for 7 d to induce the UC model.On the 1st day of DSS administration,the mice in treatment groups received the corresponding agents via oral gavage for 10 d,while those in NC and model groups were gavaged with distilled water.Throughout the study,the effects of PHSTF on body weight,fecal blood,and colon length were measured and recorded daily.Histopathological changes in colon tissues were assessed using hematoxylin-eosin staining.The levels of the pro-inflammatory cytokine interleukin-1β(IL-1β)and the anti-inflammatory cytokine IL-10 in colon tissues were quantified using ELISA.The LPS-induced RAW264.7 macrophage model was employed to evaluate the cellular effects of PHSTF.Cell viability was assessed by CCK-8 assay,and cell morphology was observed under a microscope.The mRNA expression of inflammatory markers[IL-1β,inducible nitric oxide synthase(iNOS),IL-10 and arginase-1(Arg-1)]was measured by RT-qPCR.Western blot and immunofluorescence double labeling were used to detect the protein expression of macrophage polarization markers(iNOS,CD206 and Arg-1).Finally,immunohistochemistry(IHC)was utilized to as-sess protein expression of iNOS in colon tissues.RESULTS:Compared to the DSS-induced UC model group,PHSTF sig-nificantly improved several parameters,including weight loss(P<0.05),rectal bleeding,and colon shortening in DSS-treated mice.PHSTF also reduced histopathological damage and inflammatory cell infiltration in the colon.It decreased IL-1β levels(P<0.05)and increased IL-10 levels(P<0.05)in colon tissues.In LPS-induced RAW264.7 cells,PHSTF reduced the mRNA expression of IL-1β and iNOS(P<0.01),while upregulating the mRNA expression of IL-10 and Arg-1(P<0.01).Additionally,PHSTF decreased iNOS protein expression(P<0.01)and elevated the expression of Arg-1 and CD206 proteins(P<0.01).IHC analysis further confirmed that PHSTF downregulated iNOS protein expression in colon tissues.CONCLUSION:Treatment with PHSTF promotes the polarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype,thereby alleviating inflammation in colon tissue and ameliorating ulcer-ative colitis in mice.

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

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 summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective:To investigate lymph node metastasis(LNM)in the prostatic anterior fat pad(PAFP)of PCa patients after robot-assisted radical prostatectomy(RARP),and analyze the clinicopathological features and prognosis of LNM in the PAFP.Methods:We retrospectively analyzed the clinicopathological data on 1 003 cases of PCa treated by RARP in the Department of Urolo-gy of PLA General Hospital from January 2017 to December 2022.All the patients underwent routine removal of the PAFP during RARP and pathological examination,with the results of all the specimens examined and reported by pathologists.Based on the pres-ence and locations of LNM,we grouped the patients for statistical analysis,compared the clinicopathological features between different groups using the Student's t,Mann-Whitney U and Chi-square tests,and conducted survival analyses using the Kaplan-Meier and Log-rank methods and survival curves generated by Rstudio.Results:Lymph nodes were detected in 77(7.7％)of the 1 003 PAFP samples,and LNM in 11(14.3％)of the 77 cases,with a positive rate of 1.1％(11/1 003).Of the 11 positive cases,9 were found in the upgraded pathological N stage,and the other 2 complicated by pelvic LNM.The patients with postoperative pathological stage≥T3 constituted a significantly higher proportion in the PAFP LNM than in the non-PAFP LNM group(81.8％[9/11]vs 36.2％[359/992],P=0.005),and so did the cases with Gleason score ≥8(87.5％[7/8]vs 35.5％[279/786],P=0.009).No statisti-cally significant differences were observed in the clinicopathological features and biochemical recurrence-free survival between the pa-tients with PAFP LNM only and those with pelvic LNM only.Conclusion:The PAFP is a potential route to LNM,and patients with LNM in the PAFP are characterized by poor pathological features.There is no statistically significant difference in biochemical recur-rence-free survival between the patients with PAFP LNM only and those with pelvic LNM only.Routine removal of the PAFP and inde-pendent pathological examination of the specimen during RARP is of great clinical significance.

OBJECTIVE To understand the current management status of the special campaign for enhancing the pathogen detection rate before antimicrobial therapy in hospitalized patients in China,analyze identified issues dur-ing implementation,and propose improvement suggestions.METHOD A questionnaire survey was conducted to collect data from medical institutions participating in the special campaign within the region from May to Jul.2024,covering aspects such as quality control management,coordination mechanisms,data sources,indicator connotations and existing issues.RESULTS Variations were observed among medical institutions in the manage-ment of pathogen detection rates,primarily reflected in inconsistent usage of detection rate indicators,varying im-plementation levels of quality control measures and differences in multi-departmental participation.Additionally,discrepancies in data sources,statistical methods and interpretations of indicator connotations limited the compara-bility of data.CONCLUSIONS To address these issues,improvement measures such as strengthening informatiza-tion construction,standardizing indicator statistical methods and enhancing multi-departmental coordination mech-anisms should be implemented.These efforts will provide a scientific basis for the implementation of special cam-paign and robust support for the rational use of antimicrobial agents.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Objective:To understand the burden of cancer disease in Hebei Province in recent years and to analyze the change trend of cancer in Hebei Province from 2011 to 2020.Methods:The incidence and death data of cancer were collected from 38 cancer registries in Hebei Province during 2011-2020. The incidence (mortality) rate, standardized incidence (mortality) rate and composition ratio of each region, sex, and age were calculated respectively, and the incidence and death of major cancers in our province were summarized. The age-standardized morbidity (mortality) rates of China and the world population were calculated using the 2000 China standard population composition and Segi's world population composition respectively. Trend analysis of morbidity and mortality was performed and average annual percentage change (AAPC) was calculated.Results:In 2020, the crude cancer incidence rate and the age-standardized morbidity rate of China was 229.36/100 000 and 147.06/100 000, respectively. An estimated 171 600 new cases were reported in the province. The crude cancer mortality rate and the age-standardized mortality rates of China was 146.38/100 000 and 85.33/100 000. The estimated number of deaths in the province is 108 900. In the cancer registration areas of Hebei Province, 84% of all cancer patients occurred in people 50 years of age and older. From 2011 to 2020, the incidence and mortality of cancer in Hebei Province showed a decreasing trend. The AAPC was -4.2% ( P＜0.001), which decreased from 206.61/100 000 in 2011 to 143.74/100 000 in 2020. The world standard mortality rate of cancer was 147.69/100 000 in 2011, and decreased to 84.79/100 000 in 2020. The AAPC was -5.7% ( P＜0.001). The world-standard incidence and mortality of lung cancer, esophageal cancer, gastric cancer, liver cancer and colorectal cancer decreased from 2011 to 2020. The AAPCs of the world-standard incidence were -4.0%, -12.3%, -9.4%, -6.0% and -1.6%, respectively. The AAPCs of the world-standard mortality were -4.9%, -11.3%, -8.5%, -5.7% and -3.3%, which were statistically significant. The incidence of thyroid cancer increased rapidly, the AAPC of which was 9.7% ( P＜0.001). The rates of female breast cancer and male prostate cancer in Hebei Province were stable. Conclusions:The world-standard incidence and mortality of cancer in Hebei Provincial cancer registries areas show a downward trend from 2011 to 2020. However, the cancer incidence and mortality in Hebei Province are still at high levels. It's necessary to strengthen cancer prevention and control in Hebei Province, improve the awareness of cancer prevention and control in the whole society, and promote the concept of tertiary cancer prevention to reduce the cancer burden in Hebei Province.

Objective:To screen novel diagnostic marker or therapeutic target for multiple myeloma(MM).Methods:Sel1L,SPAG4,KCNN3 and PARM1 were identified by bioinformatics method based on GEO database as high expression genes in MM.Their RNA and protein expression levels in bone marrow mononuclear cells from myeloma cell lines U266,NCI-H929,MM.1s,RPMI8226 and leukemia cell line THP1,as well as 31 MM patients were evaluated by RT-PCR and Western blot,respectively.Meanwhile,5 samples of bone marrow from healthy donors for allogeneic hematopoietic stem cell transplantation were employed as controls.Results:Compared with leukemia cell line THP1,the expression levels of KCNN3,PARM1 and Sel1L mRNA were significantly increased in myeloma cell lines U266,NCI-H929 and MM.1s,while PARM1 was further increased in myeloma cell lines 8226.Western blot showed that the 4 genes were all expressed in the 4 myeloma cell lines.Compared with healthy controls,the expression levels of Sel1L,SPAG4,KCNN3 and PARM1 mRNA were significantly higher in MM patients(all P＜0.05).Western blot showed that the 4 genes were all expressed in MM patients,and the protein expression level of Sel1L and KCNN3 were significantly different compared with healthy donors(all P＜0.01).Conclusion:Sel1L,SPAG4,KCNN3 and PARM1 may be potential diagnostic markers and therapeutic targets for MM.