Objective To analyze the efficacy and safety of ustekinumab(UST)in patients with moderate-to-severe Crohn's disease(CD),and to identify factors influencing clinical outcomes.Methods Data were retrospectively collected from patients with moderate-to-severe CD treated with UST in the First Affiliated Hospital of Zhejiang Chinese Medical University and Hangzhou Hospital of Traditional Chinese Medicine between November 2020 and May 2023.Patients were categorized into first-line(not treated with biologic agents,n=68)and second-line(treated with biologic agents,n=66)treatment groups based on prior use of biologic agents.Baseline characteristics,including age,sex,smoking status,disease duration,age at diagnosis,lesion site,disease behavior,perianal disease,history of intestinal surgery,and CD-related drug use,were compared between the two groups.Crohn's disease activity indices(CDAI)were recorded at baseline,week 14,and week 52 to assess the clinical efficacy at weeks 14 and 52.Endoscopic evaluations were performed at baseline and week 52 to evaluate endoscopic efficacy at week 52.The 52-week drug persistence rate and safety profile were also analyzed.Influencing factors related to clinical outcomes were evaluated using univariate and multivariate logistic regression.Results A total of 134 patients with moderate-to-severe CD treated with UST were included.At week 14,clinical response and remission rates were 75.4%(101/134)and 33.6%(45/134),respectively,with no significant difference in clinical efficacy between first-line and second-line groups(clinical response rate:77.9%vs.72.7%,P=0.484;clinical remission rate:38.2%vs.28.8%,P=0.247).At week 52,clinical response and remission rates were 79.9%(107/134)and 56.0%(75/134),respectively.The rates of endoscopic response and remission were 70.9%(95/134)and 38.8%(52/134),respectively.There were no significant differences in clinical efficacy(clinical response rate:80.9%vs.78.8%,P=0.763;clinical remission rate:60.3%vs.51.5%,P=0.306)and endoscopic efficacy(endoscopic response rate:76.5%vs.65.2%,P=0.149;endoscopic remission rate:42.6%vs.34.8%,P=0.354)between the two groups.The 52-week drug persistence rate was 85.8%(115/134),and the adverse reaction rate was 4.5%(6/134).Compared with first-line treatment group,biologic-experienced patients had a significantly higher proportion of dose-optimized therapy in second-line treatment group(45.5%vs.22.1%,P=0.004).Multivariate logistic regression showed that the 14-week clinical response was a significant predictor of 52-week clinical remission,while perianal disease and intestinal surgery history were significant factors associated with treatment failure(P<0.05).Conclusions UST demonstrates significant efficacy in improving clinical and endoscopic outcomes for moderate-to-severe CD patients,with a favorable safety profile.Clinical response at 14 weeks is strongly predictive of clinical remission at 52 weeks.Patients with perianal disease or a history of intestinal surgery were at higher risk of treatment failure.

Objective To investigate the clinical characteristics of preoperative intestinal symptoms in patients with bowel endometriosis and to compare the effects of shaving versus segmental bowel resection on postoperative intestinal function.Methods A total of 105 patients diagnosed with bowel endometriosis and treated by the same surgical team at the Obstetrics and Gynecology Hospital,Fudan University between Aug 1,2013 and Dec 30,2017 were prospectively enrolled in this study.Clinical data were collected via outpatient visits and telephone follow-ups at four time points:preoperative(T0)and postoperative(T1:Nov 2018;T2:Nov 2020;T3:Apr 2024).The primary outcome was bowel symptoms and gastrointestinal function scores;secondary outcome was pain scores.A generalized estimating equation(GEE)model was used to analyze the interaction effect of surgical approach and follow-up time on outcomes.Results Ultimately,a total of 89 patients were included(15.24%loss to follow-up),among whom 79 patients(88.76%)underwent shaving excision.Preoperatively,46 patients(51.68%)presented with bowel symptoms,primarily anus bulge(21 cases,46.65%)and diarrhea(15 cases,32.61%)during menstruation.Postoperatively,there was a significant increase in constipation rates(T1:71.43%;T2:50.00%;T3:72.00%).Both surgical groups exhibited significant improvements in dysmenorrhea,gastrointestinal discomfort scores as well as gastrointestinal quality of life index(P<0.000 5).However,the segmental resection group had significantly higher scores for low anterior resection syndrome,constipation compared with the shaving excision group(P=0.02 and P=0.05).Conclusion Approximately half of the patients with bowel endometriosis exhibit typical bowel symptoms preoperatively,such as anus bulge and diarrhea.Both shaving excision and segmental resection effectively alleviate pain;however,shaving excision demonstrates an advantage regarding preservation of bowel function,whereas segmental resection may elevate risks associated with postoperative constipation or altered defecation patterns due to structural changes.The selection of surgical approach should carefully balance lesion removal and functional preservation,moreover,be sure that potential risks are thoroughly informed to patients prior to surgery.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To explore the effect of the Nurse-Mini-CEX assessment method combined with PBL teaching mode in the cultivation of core competencies of undergraduate nursing students during ICU internships.Methods:A total of 64 nursing students interning in the ICU of a Third-grade Class-A hospital in Wuhu City from Sep 2022 to Aug 2023 were selected and randomly divided into 8 groups(8 students in each group).Using cluster sampling,4 groups(32 students)were assigned to the experimental group,receiving training via Nursing-Mini-CEX combined with PBL,while the remaining 4 groups(32 students)served as the control group,undergoing traditional clinical teaching.All students completed a 2-month pre-ICU clinical internship,followed by a 4-week ICU internship.Results:Compared to the control group,the experimental group showed significantly higher scores in five dimensions of nursing competency:nursing consultation,nursing physical examination,nursing diagnosis,nursing interventions,and holistic evaluation(P＜0.05).Additionally,the experimental group outperformed the control group in core competencies,including clinical nursing skills,leadership,interpersonal communication,professional development,critical thinking and research ability(P＜0.05).Self-efficacy in learning ability and behavior,as well as scores in personal accomplishment,depersonalization,and emotional exhaustion,were also higher in the experimental group(P＜0.05).Furthermore,the experimental group reported greater satisfaction with training content,teaching effectiveness,clinical skill development,teamwork cultivation,and overall satisfaction(P＜0.05).Conclusions:Nursing-Mini-CEX assessment combined with PBL teaching mode effectively enhances core competencies and self-efficacy,reduces burnout among ICU nursing interns,and achieve good clinical results,providing a theoretical and practical basis for the teaching and training of nursing students in ICU.However,as a single-center study,further validation and broader studies are warranted.

Dark plum can be used to treat symptoms such as consumptive thirst due to deficiency-heat and chronic cough due to lung deficiency.Its active ingredients have auxiliary effects on lowering blood glucose,antibacterial and anti-inflammatory activities.Insulin resistance is mainly characterized by the weakening of the physiological effects of insulin in the body,with a relatively complex mechanism that can lead to various metabolic-related diseases and seriously affect health.The active ingredients of dark plum can improve insulin resistance by regulating insulin signaling pathways,endoplasmic reticulum stress,antioxidant stress,inflammatory signaling pathways,levels of related inflammatory mediators,and free fatty acid levels.By reviewing the relevant literature on the improvement of insulin resistance by the active ingredients of dark plum,this article summarizes and analyzes its mechanism of action,aiming to provide new ideas and scientific evidence for in-depth research on insulin resistance and the development and application of drugs.

Aim To clarify the mechanism by which Qishen Yixin Granules improved microcirculation vas-cular endothelial dysfunction(VED)in mice,through activating the Nrf2/HO-1 signaling pathway to regulate oxidative stress.Methods C57 mice were randomly divided into six groups:blank group,model group,pos-itive drug group,and low-,medium-,and high-dose groups of Qishen Yixin Granules.The VED model was established by long-term infusion of Ang Ⅱ combined with a high-fat diet.Each treatment group received the corresponding drug intervention.After four weeks of drug intervention,cardiac function was assessed by echocardiography.Carstairs staining was used to ob-serve the formation of microthrombi in myocardial tis-sue.The micro vascular ischemia was evaluated by Hei-denhain staining.The ultrastructure of endothelial cells was observed by electron microscopy.The levels of EMPs,ROS,NO,ET-1,TF,TM,VWF,and TXA2 in serum were measured by ELISA.The expression levels of MDA,SOD,and GSH-Px in mouse heart tissue were determined by chemical methods.Cardiac microvascu-lar density and the expression of Nrf2,Keap1,and HO-1 proteins were detected by Immunohistochemical stai-ning.The protein expressions of Keap1,cytoplasmic Nrf2,nuclear Nrf2,and HO-1 in myocardial tissue were detected by Western blot.Results Qishen Yixin Granules could effectively improve the cardiac function of mice,alleviate the damage of endothelial cells and endothelial function.They could up-regulate serum NO levels and the activities of antioxidant enzymes SOD and GSH-Px,while down-regulating the expression of ROS and vascular inflammatory injury factors such as ET-1,VWF,TXA2,TF,TM,and EMPs.Qishen Yixin Granules also increased the positive counts of CD34,Nrf2,and HO-1,as well as microvessel density.Fur-thermore,they inhibited the expression of MDA,Keap1,and cytoplasmic Nrf2 protein in myocardial tis-sue,while increasing the expression of nuclear proteins HO-1 and Nrf2.Conclusions Qishen Yixin Granules may inhibit oxidative stress and inflammatory response by regulating the Nrf2/HO-1 signaling pathway,thereby improving vascular endothelial damage and cardiac function in VED mice.

Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

OBJECTIVE: To systematically search and integrate the best evidence for early rehabilitation of ICU-acquired swallowing dysfunction (ICU-ASD) using evidence-based medicine methods, providing high-quality evidence-based support for intensive care unit (ICU) healthcare professionals in implementing early rehabilitation assessment and intervention strategies for ICU-ASD. METHODS: The systematic search was conducted according to the "6S" pyramid evidence model. Multiple authoritative databases and resources were comprehensively searched, including: National Guideline Clearinghouse (NGC), National Institute for Health and Care Excellence (NICE), Canadian Medical Association Clinical Practice Guidelines Library (CMACPGL), New Zealand Guidelines Group (NZGG), Guidelines International Network (GIN), Registered Nurses' Association of Ontario (RNAO), Scottish Intercollegiate Guidelines Network (SIGN), PubMed/Medline, Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, JBI Evidence-Based Health Care Database, Physiotherapy Evidence Database (PEDro), Chinese Medical Pulse Guidelines Website, SinoMed, CNKI, Wanfang Data, UpToDate, BMJ Best Practice, and professional association websites. The search encompassed guidelines, expert consensus statements, original studies [including cohort studies, quasi-experimental studies, and randomized controlled trials (RCT)], systematic reviews, and evidence summaries related to the prevention and management of ICU-ASD. The search period was limited from the inception of each database to November 30, 2024. The best evidence for early rehabilitation of ICU-ASD was summarized. The quality assessment of the literature and the extraction and synthesis of evidence were independently performed by two researchers with expertise in evidence-based medicine methodology. RESULTS: A total of 16 articles were included, consisting of 1 clinical decision-making study, 1 cohort study, 2 guidelines, 2 RCTs, 6 systematic reviews, 1 evidence summary, 2 expert consensuses, and 1 expert opinion. Following quality assessment, all 16 articles were incorporated into the analysis. For the early rehabilitation of ICU-ASD, five major themes were ultimately identified and 25 best evidence items were summarized, focusing on: multidisciplinary collaboration, swallowing screening and assessment, rehabilitation interventions, dietary and nutritional management, and oral hygiene. CONCLUSIONS The evidence summary provides individualized rehabilitation strategies for ICU-ASD patients, but their implementation still needs to be adapted to China's clinical practice context and patient preferences.
Humans ; Deglutition Disorders/etiology* ; Intensive Care Units ; Evidence-Based Medicine

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

This study explores the effect and mechanism of Banxia Xiexin Decoction(BXD) in inhibiting colon cancer progression by reshaping tryptophan metabolism. Balb/c mice were assigned into control, model, low-dose BXD(BXD-L), and high-dose BXD(BXD-H) groups. Except the control group, the other groups were subcutaneously injected with CT26-Luc cells for the modeling of colon cancer, which was followed by the intervention with BXD. Small animal live imaging was employed to monitor tumor growth, and the tumor volume and weight were measured. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in mouse tumors. Immunohistochemistry was used to detect Ki67 expression in tumors. Immunofluorescence and flow cytometry were used to detect the infiltration and number changes of CD3~+/CD8~+ T cells in the tumor tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interferon-gamma(IFN-γ) and interleukin-2(IL-2) in tumors. Targeted metabolomics was employed to measure the level of tryptophan(Trp) in the serum, and the Trp content in the tumor tissue was measured. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of indoleamine 2,3-dioxygenase 1(IDO1), MYC proto-oncogene, and solute carrier family 7 member 5(SLC7A5) in the tumor tissue. Additionally, a co-culture model with CT26 cells and CD8~+ T cells was established in vitro and treated with the BXD-containing serum. The cell counting kit-8(CCK-8) assay was used to examine the viability of CT26 cells. The content of Trp in CT26 cells and CD8~+ T cells, as well as the secretion of IFN-γ and IL-2 by CD8~+ T cells, was measured. RT-qPCR was used to determine the mRNA levels of MYC and SLC7A5 in CT26 cells. The results showed that BXD significantly inhibited the tumor growth, reduced the tumor weight, and decreased the tumor volume in the model mice. In addition, the model mice showed sparse arrangement of tumor cells, varying degrees of patchy necrosis, and downregulated expression of Ki67 in the tumor tissue. BXD elevated the levels of IFN-γ and IL-2 in the tumor tissue, while upregulating the ratio of CD3~+/CD8~+ T cells and lowering the levels of Trp, IDO1, MYC, and SLC7A5. The co-culture experiment showed that BXD-containing serum reduced Trp uptake by CT26 cells, increased Trp content in CD8~+T cells, enhanced IL-2 and IFN-γ secretion of CD8~+T cells, and down-regulated the mRNA levels of MYC and SLC7A5 in CT26 cells. In summary, BXD can inhibit the MYC/SLC7A5 pathway to reshape Trp metabolism and adjust Trp uptake by CD8~+ T cells to enhance the cytotoxicity, thereby inhibiting the development of colon cancer.
Animals ; Tryptophan/metabolism* ; Colonic Neoplasms/pathology* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred BALB C ; Humans ; Cell Line, Tumor ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Female ; Disease Progression ; Cell Proliferation/drug effects* ; Proto-Oncogene Mas ; Male