Objective To investigate the causal relationship between gut microbiota and idiopathic pulmonary fibrosis (IPF). Methods Genome-wide association studies (GWAS) data of gut microbiota and IPF were obtained from MiBioGen and IEU OpenGWAS, respectively. Instrumental variables were screened by means of significance, linkage disequilibrium, weak instrumental variable screening, and removal of confounding factors (genetics, smoking, host characteristics). Inverse variance weighted (IVW) was used as the main Mendelian randomization (MR) analysis method, and the weighted median, simple mode, MR-Egger, and weighted mode were used to perform MR to reveal the causal effect of gut microbiota and IPF. The Cochrane's Q, leave-one-out, MR-Egger-intercept, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and Steiger tests were used to analyze the heterogeneity, horizontal pleiotropy, outliers, and directionality, respectively. Results IVW analysis results showed that Actinobacteria [OR=1.773, 95%CI (1.323, 2.377), P<0.001], Erysipelatoclostridium [OR=2.077, 95%CI (1.107, 3.896), P=0.023], and Streptococcus [OR=1.35, 95%CI (1.100, 1.657), P=0.004] could increase the risk of IPF. Bifidobacterium [OR=0.668, 95%CI (0.620, 0.720), P<0.001], Ruminococcus [OR=0.434, 95%CI (0.222, 0.848), P=0.015], and Tyzzerella [OR=0.479, 95%CI (0.304, 0.755), P=0.001] could reduce the risk of IPF. No significant heterogeneity, horizontal pleiotropy, outliers, and reverse causality were found. Conclusion Actinobacteria, Erysipelatoclostridium and Streptococcus may increase the risk of IPF, while Bifidobacterium, Ruminococcus and Tyzzerella may reduce the risk of IPF. Regulation of the above gut microbiota may become a new direction in the study of the pathogenesis of IPF.

Lipocalin-2 (LCN2), a member of the human lipocalin family, has been demonstrated to be closely associated with diabetes, cardiovascular diseases, and renal disorders. Recent studies have indicated that LCN2 plays a significant regulatory role in the pathogenesis and progression of various neurological diseases by mediating pathways such as inflammation, oxidative stress, and ferroptosis. This article reviews the research advancements on the mechanism of LCN2 in neurological disorders, including cerebrovascular diseases, cognitive impairment disorders, Parkinson's disease, depression, and anxiety disorders, aiming to enhance clinical understanding.

The aim of this experiment was to investigate the effects of daidzein(DZ)on mammary gland development in mice during pregnancy.A total of 36 pregnant mice were randomly divided into a control group(treated with sterile PBS),a DZ group(DZ working fluid by intraperitoneal injection)and a E2 group(E2 working fluid by intraperitoneal injection),once daily,for 7 days.Af-ter normal delivery of pregnant mice,6 mice were selected from each group on the 1st and 10th day of the lactation period,then executed after blood sampling,and all mammary gland tissue were taken for the following experiments:1)mammary gland tissue was weighted and the mammary gland index was calculated;preparation of mammary gland tissue sections,HE staining;2)ELISA of estradiol,prolactin and insulin-like growth factor concentrations in serum;3)Western blot and RT-qPCR were used to analyze the expression of cell cyclin proteins and ER-a,ER-β proteins and genes in mammary gland tissues.The results showed that:compared with control group,DZ signif-icantly increased the area ratio of acinar in the mammary gland of mice(P＜0.05),decreased the area ratio of adipose tissue and increased proliferative expansion of adenohypophysis;DZ highly significantly increased serum PRL levels(P＜0.01)and serum IGF-1 content,reduced serum E2 levels;DZ significantly up-regulated the expression of CyclinD1,CyclinD3,PCNA and ER-β pro-teins(P＜0.05),and the mRNA level of ER-β gene was significantly up-regulate(P＜0.01).In conclusion,DZ can promote cell proliferation and division by increasing the expression of cell cycle proteins and proliferation proteins,promotes the proliferation of mammary gland follicles and in-creases mammary gland weight during pregnancy in mice,and at the same time increase the serum levels of IGF-1 and PRL in the female rats,which jointly promote the development of the mamma-ry glands during lactation.

Background and Aims:Unplanned reoperation is a critical indicator for evaluating the quality of surgical treatment and prognosis in patients with gastrointestinal perforation.Identifying its underlying causes,recognizing relevant risk factors,and developing effective preventive strategies are essential for optimizing treatment outcomes and improving patient prognosis.This study aimed to investigate the causes and risk factors of unplanned reoperation following surgery for gastrointestinal perforation,in order to provide clinical guidance for targeted interventions.Methods:The clinical data of 303 patients who underwent surgery for gastrointestinal perforation at the Department of General Surgery,Shijiazhuang People's Hospital,from January 2020 to July 2023,were retrospectively analyzed.Among them,218 were males and 85 were females,with a mean age of(61.05±17.95)years.Seventeen patients experienced unplanned reoperations after operation,while 286 did not.Univariate analysis and multivariate Logistic regression were performed to identify the risk factors associated with unplanned reoperation.A predictive model was developed and its performance was assessed using the receiver operating characteristic(ROC)curve.Results:Among the 17 patients who underwent unplanned reoperation,14 were males and 3 were females,with a mean age of(65.76±15.11)years.The primary causes of reoperation included postoperative fistula(7 cases),postoperative bleeding(4 cases),surgical site infection(2 cases),wound dehiscence(2 cases),and stoma-related complications(2 cases).Univariate analysis indicated that gender,comorbidities,hypoproteinemia,history of abdominal surgery,ASA score,surgical grade,and disease duration were significantly associated with unplanned reoperation(all P<0.05).Multivariate Logistic regression revealed that male gender(OR=99.62,95%CI=4.90-2 025.29,P<0.05),hypoproteinemia(OR=8.59,95%CI=1.81-40.91,P<0.05),history of abdominal surgery(OR=17.28,95%CI=3.42-87.32,P<0.05),higher ASA score(OR=11.89,95%CI=2.73-51.72,P<0.05),higher surgical grade(OR=17.15,95%CI=2.47-118.93,P<0.05),and longer disease duration(OR=1.04,95%CI=1.02-1.07,P<0.05)were independent risk factors.The ROC curve analysis showed that the predictive model constructed based on the above factors had a sensitivity of 0.90,a specificity of 0.88,and an area under the curve of 0.94(95%CI=0.88-0.99,P<0.001).Conclusion:The leading causes of unplanned reoperation after gastrointestinal perforation surgery are postoperative fistula and bleeding.Male gender,hypoproteinemia,and other high-risk factors significantly increase the likelihood of reoperation.Although most such surgeries are performed emergently,comprehensive preoperative assessment of relevant risk factors is crucial to reduce the incidence of unplanned reoperation,and improve patient outcomes.

The aim of this experiment was to investigate the effects of daidzein(DZ)on mammary gland development in mice during pregnancy.A total of 36 pregnant mice were randomly divided into a control group(treated with sterile PBS),a DZ group(DZ working fluid by intraperitoneal injection)and a E2 group(E2 working fluid by intraperitoneal injection),once daily,for 7 days.Af-ter normal delivery of pregnant mice,6 mice were selected from each group on the 1st and 10th day of the lactation period,then executed after blood sampling,and all mammary gland tissue were taken for the following experiments:1)mammary gland tissue was weighted and the mammary gland index was calculated;preparation of mammary gland tissue sections,HE staining;2)ELISA of estradiol,prolactin and insulin-like growth factor concentrations in serum;3)Western blot and RT-qPCR were used to analyze the expression of cell cyclin proteins and ER-a,ER-β proteins and genes in mammary gland tissues.The results showed that:compared with control group,DZ signif-icantly increased the area ratio of acinar in the mammary gland of mice(P＜0.05),decreased the area ratio of adipose tissue and increased proliferative expansion of adenohypophysis;DZ highly significantly increased serum PRL levels(P＜0.01)and serum IGF-1 content,reduced serum E2 levels;DZ significantly up-regulated the expression of CyclinD1,CyclinD3,PCNA and ER-β pro-teins(P＜0.05),and the mRNA level of ER-β gene was significantly up-regulate(P＜0.01).In conclusion,DZ can promote cell proliferation and division by increasing the expression of cell cycle proteins and proliferation proteins,promotes the proliferation of mammary gland follicles and in-creases mammary gland weight during pregnancy in mice,and at the same time increase the serum levels of IGF-1 and PRL in the female rats,which jointly promote the development of the mamma-ry glands during lactation.

Background and Aims:Unplanned reoperation is a critical indicator for evaluating the quality of surgical treatment and prognosis in patients with gastrointestinal perforation.Identifying its underlying causes,recognizing relevant risk factors,and developing effective preventive strategies are essential for optimizing treatment outcomes and improving patient prognosis.This study aimed to investigate the causes and risk factors of unplanned reoperation following surgery for gastrointestinal perforation,in order to provide clinical guidance for targeted interventions.Methods:The clinical data of 303 patients who underwent surgery for gastrointestinal perforation at the Department of General Surgery,Shijiazhuang People's Hospital,from January 2020 to July 2023,were retrospectively analyzed.Among them,218 were males and 85 were females,with a mean age of(61.05±17.95)years.Seventeen patients experienced unplanned reoperations after operation,while 286 did not.Univariate analysis and multivariate Logistic regression were performed to identify the risk factors associated with unplanned reoperation.A predictive model was developed and its performance was assessed using the receiver operating characteristic(ROC)curve.Results:Among the 17 patients who underwent unplanned reoperation,14 were males and 3 were females,with a mean age of(65.76±15.11)years.The primary causes of reoperation included postoperative fistula(7 cases),postoperative bleeding(4 cases),surgical site infection(2 cases),wound dehiscence(2 cases),and stoma-related complications(2 cases).Univariate analysis indicated that gender,comorbidities,hypoproteinemia,history of abdominal surgery,ASA score,surgical grade,and disease duration were significantly associated with unplanned reoperation(all P<0.05).Multivariate Logistic regression revealed that male gender(OR=99.62,95%CI=4.90-2 025.29,P<0.05),hypoproteinemia(OR=8.59,95%CI=1.81-40.91,P<0.05),history of abdominal surgery(OR=17.28,95%CI=3.42-87.32,P<0.05),higher ASA score(OR=11.89,95%CI=2.73-51.72,P<0.05),higher surgical grade(OR=17.15,95%CI=2.47-118.93,P<0.05),and longer disease duration(OR=1.04,95%CI=1.02-1.07,P<0.05)were independent risk factors.The ROC curve analysis showed that the predictive model constructed based on the above factors had a sensitivity of 0.90,a specificity of 0.88,and an area under the curve of 0.94(95%CI=0.88-0.99,P<0.001).Conclusion:The leading causes of unplanned reoperation after gastrointestinal perforation surgery are postoperative fistula and bleeding.Male gender,hypoproteinemia,and other high-risk factors significantly increase the likelihood of reoperation.Although most such surgeries are performed emergently,comprehensive preoperative assessment of relevant risk factors is crucial to reduce the incidence of unplanned reoperation,and improve patient outcomes.

Objective:To investigate the heterogeneity of FLT3 mutations and the consequences of co-occurring mutations on the clinical features and prognosis of patients with acute myeloid leukemia(AML).Methods:We retrospectively analyzed the clinical characteristics of 80 patients with AML who carried FLT3 mutations,as detected by genetic testing,and were treated in The First Hospital of Lanzhou Uni-versity from October 2017 to March 2024.An analysis was performed to evaluate the impact of FLT3 mutation frequency,insertion length of base pairs,insertion site,and co-occurring mutations on survival outcomes.Results:The variant allele frequency(VAF)of FLT3-ITD muta-tions was correlated with leukocyte counts and lactate dehydrogenase levels in patients with de novo AML.There was an association between the insertion site and the length of the base-pair insertion.Patients with AML who also had a VAF of FLT3-ITD mutations greater than or equal to 0.38 exhibit reduced overall survival(OS),whereas the length of base pair insertion,insertion site,and number of muta-tions did not correlate with OS.Patients with non-classical FLT3 mutations demonstrated a significantly longer OS than did those with FLT3-ITD mutations.The co-occurrence of FLT3-ITD,NPM1,and DNMT3A mutations was associated with markedly reduced OS.The use of FLT3 inhibitors and allogeneic hematopoietic stem cell transplantation(allo-HSCT)can improve the prognosis of patients with FLT3-ITD mutations.Conclusions:FLT3 mutational heterogeneity correlates with the clinical characteristics and outcomes of patients with AML.Non-classical FLT3 and FLT3-TKD mutations are associated with superior prognosis.Patients with a VAF of 0.38 or higher have a poorer prognosis,but the use of FLT3 inhibitors can improve their prognosis.Patients with triple mutations have poor prognosis.

Alzheimer's disease(AD), the most common neurodegenerative disease, has shown an increasing incidence among younger people. With the onset of disease, most patients' cognitive function will show a progressive decline, bringing a heavy burden to the society and the family. Studies have shown that fibroblast growth factor (FGF) may be involved in the pathogenesis of AD through multiple mechanisms. This article reviews the mechanism of FGF in AD, with the hope of providing new ideas for elucidating the pathogenesis and early diagnosis of AD.

Objective:To investigate the distribution characteristics of urinary tract pathogens in patients with community-acquired urinary tract infection and their sensitivity to nenoxacin and levofloxacin.Methods:This prospective, multicenter clinical trial included patients with community-acquired urinary tract infection who were admitted to urological clinics at 9 clinical research centers from November 2021 to August 2022.Inclusion criteria: Patients aged 18-70 years with community-acquired acute uncomplicated cystitis(AUC), recurrent acute episodes of urinary tract infection(rUTI), and non-febrile complicated urinary tract infection(cUTI) with signs of urinary tract irritation and abnormal elevation of routine white blood cells in urine. Exclusion criteria: ①Patients who received effective antimicrobial therapy within 72 h before enrollment and lasted for more than 24 h. ②Fever (>37.3℃) or symptoms of upper urinary tract infection such as low back pain, tapping pain in the kidney area, etc. ③Indwelling urinary catheter. At the first visit, clean midstream urine samples were taken for bacterial culture, and the distribution characteristics of urinary pathogens of different types of urinary tract infections were analyzed. Extended spectrum β-lactamases (ESBLs) were measured for Gram-negative bacteria. The susceptibility of nenoxacin and levofloxacin to urinary tract pathogens was determined by disk diffusion method. Drug resistance rate, sensitivity rate were analyzed between different disease groups.Results:There were 404 enrolled patients from 9 hospitals, including 364 (90.1%) females and 40 (9.9%) males. A total of 177 strains of pathogenic bacteria were isolated, among which the highest proportion of Escherichia coli was 66.1% (117/177).Klebsiella pneumoniae was followed by 6.8% (12/177) and Streptococcus agalactis 5.1% (9/177). The bacterial spectrum distribution of AUC and rUTI were similar, and the proportions of Escherichia coli were 70.6% (85/119) and 65.9% (29/44), respectively. However, the proportions of Escherichia coli isolated from cUTI patients were only 28.6% (4/14) and Enterococcus faecalis 7.1%(1/14). The overall detection rate of ESBLs in Gram-negative bacteria was 30.9%(43/139). The sensitivity rate of nenoxacin was 74.6%(91/122), and the resistance rate was 25.4%(31/122). The overall sensitivity rate of levofloxacin was 44.9%(70/156) and the resistance rate was 36.5%(57/156). The rate of resistance of urinary tract pathogens to levofloxacin was 48.2% (27/56) in patients with previous urinary tract infection history, and 30.0% (30/100) in patients with no previous urinary tract infection history, the difference was statistically significant( P=0.023).The sensitivity rate of Gram-negative bacteria to nenofloxacin was 70.7% (65/92) and that to levofloxacin was 50.0% (46/92, P<0.001). The sensitivity of Gram-positive bacteria to nenofloxacin was 80.0% (16/20), and that to levofloxacin was 70.0% (14/20, P=0.009). Conclusions:The bacterial profile of out-patient community acquired urinary tract infection varies greatly according to different diseases. The proportion of Escherichia coli in AUC and rUTI patients is higher than that in cUTI. The detection rate of ESBLs in Gram-negative bacteria was lower than the domestic average.Patients with a history of urinary tract infection had a high risk of treatment failure with levofloxacin. The sensitivity of common urinary tract pathogens to nenofloxacin was higher than levofloxacin.