This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

OBJECTIVE: To investigate the association between ABO blood types and gestational diabetes mellitus (GDM) risk. METHODS: A prospective birth cohort study was conducted. ABO blood types were determined using the slide method. GDM diagnosis was based on a 75-g, 2-h oral glucose tolerance test (OGTT) according to the criteria of the International Association of Diabetes and Pregnancy Study Groups. Logistic regression was applied to calculate the odds ratios ( ORs) and 95% confidence intervals ( CIs) between ABO blood types and GDM risk. RESULTS: A total of 30,740 pregnant women with a mean age of 31.81 years were enrolled in this study. The ABO blood types distribution was: type O (30.99%), type A (26.58%), type B (32.20%), and type AB (10.23%). GDM was identified in 14.44% of participants. Using blood type O as a reference, GDM risk was not significantly higher for types A ( OR = 1.05) or B ( OR = 1.04). However, women with type AB had a 19% increased risk of GDM ( OR = 1.19, 95% CI = 1.05-1.34; P < 0.05), even after adjusting for various factors. This increased risk for type AB was consistent across subgroup and sensitivity analyses. CONCLUSION The ABO blood types may influence GDM risk, with type AB associated with a higher risk. Incorporating it-either as a single risk factor or in combination with other known factors-could help identify individuals at risk for GDM before or during early pregnancy.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/etiology* ; ABO Blood-Group System ; Adult ; Prospective Studies ; Risk Factors ; Young Adult

BACKGROUND:The occurrence and development of various ophthalmic diseases are closely related to excessive oxidative stress,and the inhibition of oxidative stress response may produce preventive and therapeutic effects. OBJECTIVE:To explore the role of Pax6 gene expression on hydrogen peroxide-induced aging of mouse bone marrow mesenchymal stem cells(BM-MSCs). METHODS:Resuscitated BM-MSCs,Pax6/BM-MSCs,and shPax6/BM-MSCs were treated with hydrogen peroxide for 24 hours,and then β-galactosidase staining was performed.The proliferation index Ki67 expression and apoptosis were detected by flow cytometry.The expression of senescence-associated molecules(Wnt7a,p21,and p53)was detected by RT-PCR. RESULTS AND CONCLUSION:(1)After hydrogen peroxide treatment,the cells of the three groups showed senescence phenotype and β-galactosidase staining was positive.Compared with BM-MSCs group,the expression of positive cells in Pax6/BM-MSCs group was less and that in the shPax6/BM-MSCs group was more,and the difference was statistically significant(P<0.05).(2)The results of flow cytometry showed that compared with BM-MSCs group,the positive expression of Ki67 in the Pax6/BM-MSCs group increased and the level of apoptosis decreased,while the positive expression of Ki67 decreased and the level of apoptosis increased in the shPax6/BM-MSCs group;the difference was significantly different(P<0.05).(3)RT-PCR showed that compared with the BM-MSCs group,the expression of Wnt7a,p53,and p21 decreased in the Pax6/BM-MSCs group,while the expression of Wnt7a,p53,and p21 increased in the shPax6/BM-MSCs group;the difference was significantly different(P<0.05).(4)These findings indicate that overexpression of Pax6 can antagonize the aging progression of BM-MSCs induced by hydrogen peroxide,which may be related to Wnt signaling pathway.

OBJECTIVE To explore the action mechanism of kushenol F （KSCF） in treating ulcerative colitis （UC） in mice. METHODS The potential targets of KSCF intervening in UC were predicted with network pharmacology and molecular docking. C57BL/6J mice were randomly divided by body weight into model group， positive control group （sulfasalazine， 703 mg/kg）， KSCF group （100 mg/kg）， and normal group， with 6 mice per group. The UC model of mice was induced by dextran sulfate sodium solution. During the modeling period， the mice were given relevant medicine intragastrically， once a day， for 7 consecutive days. After the last administration， the disease activity index （DAI） of the mice was scored； the length of the mice’s colon was measured； pathological changes in the colon tissue of mice were observed； the levels of lipopolysaccharide （LPS） in serum， myeloperoxidase （MPO）， nitric oxide （NO） and superoxide dismutase （SOD） in the colon were detected in mice； the expression levels of occludin and ZO-1 in colon tissue of mice were detected； the proportions of CD3+T， CD4+T， and CD8+T lymphocytes in the spleen and the ratio of CD4+/CD8+ were detected； changes in colonic microbiota were analyzed by 16S rDNA sequencing. RESULTS Results of network pharmacology indicated that KSCF may treat UC by regulating signaling pathways such as phosphatidylinositol-3 kinase/protein kinase B （PI3K/AKT） and nuclear factor kappa B （NF- κB）. Molecular docking results showed that KSCF bound most stably with NF-κB p65 protein. Animal experiment results demonstrated that， compared with the model group， the pathological characteristics of colon tissue in mice were improved in KSCF group. DAI scores， serum levels of LPS， the levels of MPO，NF-κB p65 phosphorylation and NLRP3 protein expression in the colon， and the proportion of CD8+T lymphocytes in the spleen were reduced significantly （P＜0.05）. Body weight， SOD levels， expression levels of occludin and ZO-1 in the colon， proportions of CD3+T and CD4+T lymphocytes， and the CD4+/CD8+ ratio in the spleen were significantly increased （P＜0.05）； the abundance of Firmicutes， Actinobacteria， Akkermansia， and Lactobacillus genera were increased， while Proteobacteria decreased； the microbial community structure tended towards that of the normal group. CONCLUSIONS KSCF alleviates UC by restoring intestinal microbial imbalance， enhancing immune response， and inhibiting colonic inflammatory responses， thereby improving intestinal barrier integrity.

ObjectiveTo investigate the effect and possible mechanism of Sishenwan in ameliorating visceral sensitivity in the rat model of diarrhea-predominant irritable bowel syndrome （IBS-D） due to spleen-kidney Yang deficiency. MethodForty male SPF-grade rats were randomly assigned into five groups： blank control， model， low- （3.51 g·kg^-1） and high-dose （7.02 g·kg^-1） Sishenwan， and Peifikang （0.54 g·kg^-1） groups. Except the blank control group， the other groups underwent maternal separation stress and Sennae Folium decoction gavage for the modeling of IBS-D due to spleen-kidney Yang deficiency. After corresponding drug interventions， the general conditions of the rats were observed， and the number of defecation pellets within 6 h and the minimum threshold of abdominal withdrawal reflex （AWR） were measured. Enzyme-linked immunosorbent assay （ELISA） was used to measure the serum levels of tumor necrosis factor （TNF）-α， gastrin （GAS）， corticosterone （CORT）， and adrenocorticotropic hormone （ACTH）. Hematoxylin-eosin （HE） staining was employed to observe pathological changes in the colon tissue. Toluidine blue staining was used to assess mast cell degranulation in the colon tissue. Western blot was performed to determine the protein levels of p38 mitogen-activated protein kinase （MAPK）， c-Jun N-terminal kinase （JNK）， transient receptor potential vanilloid 1 （TRPV1）， and protease-activated receptor 2 （PAR2） in the colon tissue. Immunohistochemistry was employed to measure the protein level of TRPV1 in the colon tissue， and immunofluorescence was used to detect the positive expression of substance P （SP） and calcitonin gene-related peptide （CGRP） in the colon tissue. ResultCompared with the blank control group， the model group showed increased number of defecation pellets within 6 h （P<0.01）， decreased minimum threshold of AWR （P<0.01）， elevated serum TNF-α level （P<0.01）， lowered levels of GAS， CORT， and ACTH （P<0.05， P<0.01）， increased mast cell degranulation rate （P<0.01）， increased positive expression of TRPV1， SP， and CGRP （P<0.05， P<0.01）， and upregulated protein levels of p38 MAPK， JNK， TRPV1， and PAR2 （P<0.01）. Compared with the model group， the high-dose Sishenwan group showed increased minimum threshold of AWR （P<0.01）， reduced defecation frequency in both the high-dose Sishenwan and Peifikang groups （P<0.05， P<0.01）， lowered TNF-α level （P<0.05， P<0.01）， elevated levels of GAS， CORT， and ACTH （P<0.05， P<0.01）， decreased mast cell degranulation rate （P<0.01）， reduced positive expression of TRPV1， SP， and CGRP （P<0.05， P<0.01）， and downregulated protein levels of p38 MAPK， JNK， TRPV1， and PAR2 （P<0.05， P<0.01）. ConclusionSishenwan can ameliorate visceral sensitivity in the rat model of diarrhea-predominant irritable bowel syndrome due to spleen-kidney Yang deficiency by regulating the p38 MAPK/JNK/TRPV1 signaling pathway.

Objective:To carry out evidence-based nursing for standardized management of stress hyperglycemia in perioperative period of gastrointestinal tumor patients, and to formulate indicators, analyze obstacles and promoting factors, formulate action strategies.Methods:Guided by the Johns Hopkins evidence-based nursing model, evidence were searched, evaluated and summarized. Clinical indicators and review methods were formulated to carry out quality review. From November 2021 to April 2022, the medical staff and patients in the gastrointestinal surgery department of the First Affiliated Hospital of Anhui Medical University who met the inclusion criteria were conducted, and the incidence of compliance rate was calculated. Based on the results of the baseline review, the obstacles and contributing factors were analyzed.Results:A total of 26 pieces of best evidence were included and 14 indicators were formulated for 48 medical staff and 45 patients to clinical review, among which the compliance rate of 7 indicators was less than 60%. The main obstacle factors were lack of procedures and instruments for management of perioperative stress hyperglycemia in gastrointestinal tumor patients, lack of knowledge of medical staff, etc. The main promoting factors were organizational support, good atmosphere of medical team cooperation, strong willingness to change, etc.Conclusions:There is a big gap between the clinical practice and the best evidence of perioperative stress hyperglycemia management in patients with gastrointestinal tumor. Action strategies should be put forward for obstacles and promoting factors to promote evidence transformation.

BACKGROUND:Autoimmune regulator gene(Aire)and Wnt signaling pathway play an important role in the maintenance and differentiation of mouse embryonic stem cell pluripotency.However,whether the Wnt signal and Aire are involved in the differentiation of embryonic stem cells to thymic epithelial progenitor cells remains poorly understood. OBJECTIVE:To investigate the relationship of the Wnt signaling pathway and Aire with the differentiation of embryonic stem cells. METHODS:A two-step differentiation method was used to induce mouse embryonic stem cells to differentiate into endoderm and then into thymic epithelial progenitor cells.Mouse embryonic stem cells were infected with Aire shRNA lentivirus,and monoclonal stable strains were screened by puromycin.Mouse embryonic stem cells were collected on days 0,3 and 10 of the directed induction of differentiation after the induced differentiation by the two-step differentiation method.Cellular immunofluorescence,flow cytometry,western blot assay,and real-time qPCR were used to detect the expression changes of related genes and proteins. RESULTS AND CONCLUSION:(1)Immunofluorescence staining showed positive expression of SSEA1 and OCT4 on day 0 of targeted induction of differentiation.(2)Immunofluorescence staining showed double-positive expression of SOX17 and FOXA2 on day 3 of targeted induction of differentiation.(3)Flow cytometry results showed positive expression of EPCAM1,K5 and K8 on day 10 of targeted induction of differentiation.(4)Compared with undifferentiated mouse embryonic stem cells,the expressions of Wnt7a,β-catenin,and Gsk-3β proteins were elevated,and the expression level of Aire protein was decreased in induced differentiated thymic epithelial progenitor cells.(5)Compared with undifferentiated mouse embryonic stem cells,the expressions of Wnt7a,β-catenin,Gsk-3β and Aire mRNA were elevated in thymic epithelial progenitor cells.(6)Compared with normal cultured mouse embryonic stem cells and their ultimately differentiated thymic epithelial progenitor cells,the expression levels of Wnt7a,β-catenin and Gsk-3β proteins were reduced in mouse embryonic stem cells with knockdown of Aire genes and their final differentiated thymic epithelial progenitor cells.In conclusion,the Wnt signaling pathway and Aire are jointly involved in the process of targeted induction of differentiation of mouse embryonic stem cells into mouse thymic epithelial progenitor cells.

Intravenous thrombolysis and revascularisation are subject to strict time windows,and most patients still need to reperfuse ischaemic tissue through their own compensatory mechanisms due to subsequent re-occlusion or"no-reflow".A good collateral circulation can prolong the therapeutic window,increase the tolerance of brain tissue to ischaemia and hypoxia,and improve the prognosis,so promoting the establishment of collateral circulation to improve ischaemic tissue perfusion is a new idea in the treatment of ischaemic stroke.In this paper,we provides a review of relevant studies on methods of assessment of collateral circulation,therapeutic approaches,and clinical significance to provide guidance for the treatment of ischaemic stroke.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.