Intraflagellar transport (IFT) is a core mechanism for ciliary assembly, length maintenance, ciliary proteome homeostasis and signal transduction. Most proteins required for ciliary structure and function are synthesized in the cytoplasm. Because the ciliary compartment is separated from the cell body by the selective barrier of the transition zone, these proteins cannot freely equilibrate between the cytoplasm and the cilium. Consequently, axonemal components, membrane proteins and signaling molecules must be actively imported into cilia, retrieved from the ciliary compartment, and recycled or degraded through highly ordered transport and sorting pathways. The IFT system is mainly composed of the IFT-A complex, IFT-B complex, kinesin-2, dynein-2 and the Bardet-Biedl syndrome protein complex (BBSome). Through coordinated anterograde and retrograde transport, these modules mediate the dynamic trafficking of different classes of ciliary cargoes. Anterograde transport delivers structural and membrane-associated components from the ciliary base toward the ciliary tip, whereas retrograde transport retrieves IFT components and selected cargoes back toward the ciliary base and cytoplasm. In this way, IFT not only supports the construction of the axoneme but also contributes to the maintenance of ciliary composition and the regulation of ciliary signaling activity. In recent years, advances in cryo-electron microscopy, in situ cryo-electron tomography and single-molecule imaging have greatly improved our understanding of the molecular mechanisms underlying IFT. These approaches have revealed how IFT trains are assembled at the ciliary base, how they move along axonemal microtubule tracks, how they undergo directional switching at the ciliary tip, and how cargoes are retrieved and recycled. Among the IFT modules, IFT-B acts as the major scaffold of IFT trains. It participates in cargo loading, motor coupling and initiation of anterograde transport. IFT-A is involved in retrograde transport, membrane protein adaptor function and train remodeling. The BBSome, through reversible association with the IFT system, regulates ciliary membrane protein sorting, signaling receptor clearance and renewal of the ciliary proteome. These functions indicate that the IFT machinery is not a simple linear transport pathway, but rather a dynamic and reconfigurable transport system. The conversion of transport direction is a key step in the IFT cycle. This process is closely associated with disassembly of anterograde trains, dissociation of kinesin-2, activation of dynein-2 at the ciliary tip and reassembly of retrograde trains. In terms of pathogenic mechanisms, IFT abnormalities may cause ciliopathies through four major pathways: defects in ciliary assembly and structure, abnormal localization of ciliary cargoes, dysregulation of signaling pathways, and impaired cargo unloading and retrieval. These defects can affect multiple organ systems, including the retina, kidney, skeleton, respiratory tract, reproductive system, and neuro-metabolic system. Current therapeutic strategies are still mainly based on symptomatic support and maintenance of organ function. Overall, IFT is a dynamic transport system jointly regulated by axonemal structure, motor activity, cargo selection and cellular signaling. It links ciliary architecture with protein turnover and signaling regulation, thereby playing a fundamental role in both ciliary homeostasis and ciliopathy pathogenesis. Further elucidation of IFT regulatory mechanisms and their relationships with disease phenotypes will help promote mechanism-based classification, genetic diagnosis and precision intervention for ciliopathies.

Objective To investigate the correlation between gut microbiota characteristics and immunotherapy efficacy in patients with advanced microsatellite stable (MSS) advanced gastrointestinal tumors. Methods Thirty patients with advanced MSS gastrointestinal tumors, including fourteen cases of gastric cancer and sixteen cases of colorectal cancer, who were admitted from November 1, 2022, to July 31, 2025 were enrolled. All patients underwent gut microbiota testing and received corresponding interventions on the basis of the results, followed by treatment with antiangiogenic agents combined with immunotherapy. Some patients additionally received probiotics or fecal microbiota transplantation. The primary endpoints were disease control rate (DCR) and objective response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Univariate and multivariate Cox regression analyses were used to assess potential prognostic factors. Results Among the thirty patients, no complete response was observed. Two cases of partial response (PR), twelve cases of stable disease, and sixteen cases of progressive disease were recorded. The ORR was 6.7%, and the DCR was 46.7%. The median PFS was 6.4 months, and the median OS was 8.3 months. Both PR patients were classified as having a medium risk of gut microbiota dysbiosis and exhibited a Bacteroides-dominated enterotype. Multivariate analysis indicated that tumor type, liver metastasis, and bone metastasis were potential prognostic factors for PFS and OS. Conclusion Patients with a medium risk of gut dysbiosis may exhibit a relatively favorable response to immunotherapy, suggesting that gut microbiota status could serve as a potential biomarker for predicting treatment efficacy in advanced MSS gastrointestinal tumors.

ObjectiveTo explore the mechanism of Yishen Huashi granules in alleviating renal tubular epithelial cell injury and relieving diabetic kidney disease by regulating the mitogen-activated protein kinase （MAPK） signaling pathway. MethodsThe db/db mice of 12 weeks old were randomly assigned into model ， dapagliflozin （1.6 mg·kg^-1）， and Yishen Huashi granules （4.7 g·kg^-1）， and db/m mice were used as the control group. The general conditions of mice were observed， and fasting blood glucose and 24-h urinary protein and albumin-to-creatinine ratio （ACR） were measured at weeks 0 and 12 of administration. After 12 weeks of treatment， the levels of serum creatinine （SCr）， blood urea （UREA）， triglycerides （TG）， total cholesterol （TC）， and low density lipoprotein （LDL） were measured. The pathological changes in the renal tissue were observed by hematoxylin-eosin （HE） staining， Periodic acid-Schiff （PAS） staining， Mallory staining， and transmission electron microscopy. Real-time PCR was employed to determine the mRNA levels of monocyte chemotactic protein-1 （MCP-1） and CC chemokine receptor-2 （CCR2） in the renal tissue of mice. The immunohistochemical assay was employed to examine the expression of p38， phospho-p38 （p-p38）， MCP-1， and CCR2 in the renal tissue of mice. Western blotting was employed to measure the protein levels of p-p38， p38， MCP-1， and CCR2 in the renal tissue of mice.HK-2 cells cultured in vitro were grouped as follows： negative control， high glucose（30 mmol·L^-1）， Yishen Huashi granule-containing serum， and SB203580. After 48 h of cell culture in each group， RNA were extracted and the levels of MCP-1， and CCR2 mRNA were determined by Real-time PCR，proteins were extracted and the levels of p38， p-p38， MCP-1， and CCR2 were determined by Western blot. ResultsThe in vivo experiments showed that before treatment， other groups had higher body weight， blood glucose level， 24 h urinary protein， and ACR than the control group （P<0.05，P<0.01）. After 12 weeks of treatment， compared with the model group， the Yishen Huashi granules group showed improved general conditions， a decreasing trend in body weight， lowered levels of blood glucose， 24-h urinary protein， and ACR （P<0.01）， reduced SCr and UREA （P<0.01）， and declined levels of TC， TG， and LDL （P<0.05，P<0.01）. Compared with the model group， the Yishen Huashi granules group showed alleviated damage and interstitial fibrosis in the renal tissue as well as reductions in glomerular foot process fusion and basement membrane thickening. Moreover， the Yishen Huashi granules group showed down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01）， reduced positive expression of p-p38， MCP-1， and CCR2 （P<0.01）， and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2 （P<0.05） in the renal tissue. The cell experiment showed that compared with the high glucose group， the Yishen Huashi granule-containing serum group showcased down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01） and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2（P<0.05，P<0.01）. ConclusionYishen Huashi granules can regulate glucose-lipid metabolism， reduce 24 h urinary protein and ACR， improve the renal function， alleviate the renal tubule injury caused by high glucose， and protect renal tubule epithelial cells in db/db mice by reducing MCP-1/CCR2 activation via the p38 MAPK signaling pathway.

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

Objective:To investigate the predictive value of thromboelastogram(TEG)combined with blood D-dimer in patients with diffuse large B-cell lymphoma(DLBCL)complicated with venous thromboembolism(VTE)of lower extremities.Methods:A total of 155 patients diagnosed with DLBCL in our hospital from August 2022 to August 2024 were collected as the research objects.Among them,73 patients received lower extremity arteriovenous color Doppler ultrasound,and 14 patients with lower extremity venous thrombosis were detected,59 cases were not detected,which were included in the VTE group and non-VTE group,respectively.The TEG parameters including coagulation angle(Angle),comprehensive coagulation index(CI),clotting time(K),maximum amplitude(MA),coagulation reaction time(R),together with blood D-dimer level,international prognostic index and whether it was relapsed or refractory were compared between the two groups.Multivariate Logistic regression analysis was used to explore the independent influencing factors of VTE formation in all patients.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve was used to evaluate the predictive value of each parameter for VTE.Results:There was no significant difference in gender and age between the VTE group and the non-VET group(all P＞0.05).The number of high-risk and relapse/refractory patients in the VTE group was significantly higher than that in the non-VTE group(all P＜0.05).Angle and CI in VTE group were significantly higher than those in non-VTE group(all P＜0.05),K value and R value were significantly lower than those in non-VTE group(all P＜0.05),and blood D-dimer level was significantly higher than that in non-VTE group(all P＜0.05).Multivariate logistic regression analysis showed that R value was an independent protective factor for VTE in patients with DLBCL(OR=0.256,P＜0.05),however,Ann Arbor stage(OR=3.885,P＜0.05)was independent risk factors for VTE in patients with DLBCL.The results of ROC curve analysis showed that there was no significant difference in the sensitivity of TEG(TEG group)prediction and TEG combined with blood D-dimer level(combined group)in predicting VTE in patients with DLBCL(92.86％,85.71％)and the sensitivity of blood D-dimer level(D-dimer group)prediction(71.43％)(P＞0.05).There was no significant difference in the specificity between TEG group prediction(74.58％)and combined group prediction(81.36％),TEG group prediction and D-dimer group prediction(64.41％)(P＞0.05).However,the specificity of the combined group was higher than that of the D-dimer group(x2=4.288,P＜0.05).The AUC of the TEG group(0.901)and the combined group(0.915)was higher than that of the D-dimer group(0.692)(Z=2.647,P＜0.05;Z=3.106,P＜0.05),but there was no significant difference in AUC between TEG group prediction and combined group prediction(P＞0.05).Conclusion:TEG and blood D-dimer levels have certain predictive efficacy for VTE in DLBCL patients,but TEG combined with blood D-dimer level has higher clinical value for VTE in DLBCL patients,which is worthy of clinical promotion.

Objective:To investigate effect of comprehensive management intervention based on WeChat multimedia classroom on cardiac function and prognosis in elderly patients with acute myocardial infarction(AMI).Methods:Clinical data of 118 elderly patients diagnosed with AMI in the Second Affiliated Hospital of Chinese PLA Air Force Military Medical University between August 2021 and December 2022 were retrospectively collected.According to nursing way after operation,they were divided into control group(n=60,comprehensive management interven-tion)and intervention group(n=58,comprehensive management intervention based on WeChat multimedia class-room),both groups were intervened for 5 months.Cardiac function,exercise tolerance,compliance to rehabilita-tion management,self-efficacy and healthy behavior were compared between two groups.Kaplan-Meier survival curve was employed to compare incidence of adverse cardiovascular events during follow-up between two groups.Results:After 5-month intervention,compared with patients in control group,those in intervention group had sig-nificant higher left ventricular ejection fraction(LVEF)[(58.14±1.88)％vs.(54.48±1.34)％],6min walking distance(6MWD)[(490.41±59.59)m vs.(394.97±28.20)m],scores of compliance to rehabilitation manage-ment[(6.97±2.03)points vs.(5.03±1.40)points],General Self-Efficacy Scale(GSES)[(30.34±4.67)points vs.(23.55±4.86)points]and Health Promoting Lifestyle Profile-Ⅱ[(137.62±30.17)points vs.(115.95±22.66)points],and significant lower left ventricular end-diastolic volume(LVEDV)[(117.90±4.22)ml vs.(131.28±3.61)ml],left ventriadar end-systolic volume(LVESV)[(54.46±2.10)ml vs.(63.15±2.06)ml],serum brain natriuretic peptide(BNP)[(362.32±25.36)pg/ml vs.(567.58±21.90)pg/ml]and incidence of ad-verse cardiovascular events(6.90％vs.21.67％)(P＜0.05 or＜0.01).Conclusion:Comprehensive management intervention based on the WeChat multimedia classroom could significantly improve cardiac function,exercise toler-ance,compliance to rehabilitation,self-efficacy and healthy behavior,and reduce incidence of adverse cardiovas-cular events after operation in elderly AMI patients.

Objective To explore the characteristics and influencing factors of drug-induced liver injury(DILI)associated with the postoperative use of propacetamol,and to provide guidance for rational clinical medication.Methods A retrospective analysis was conducted on hospitalized patients who underwent surgical treatment and were administered propacetamol from January 2022 to June 2024.Cases were screened based on established inclusion and exclusion criteria.Statistical analyses were performed on patients'demographic data,medication information,liver function indicators before and after medication,comorbid conditions,and concomitant medications to assess the incidence and influencing factors of propacetamol-related DILI.A multivariate Logistic regression analysis was conducted to identify related risk factors.Results A total of 7,579 patients were sampled,of which 2,114 met the inclusion criteria.Among them,531 patients(25.1%)experienced DILI,primarily presenting with abnormal liver function indicators.This included elevated alanine aminotransferase in 379 cases(71.4%),elevated aspartate aminotransferase in 197 cases(37.1%),elevated alkaline phosphatase in 209 cases(39.4%),and elevated total bilirubin in 92 cases(17.3%).Univariate analysis revealed that there were significant differences in gender,height,age,weight,body mass index(BMI),duration of propacetamol use,total medication dosage,concomitant use of hepatic-metabolized antibiotics,and history of liver disease between the DILI group and non-DILI group(P<0.05).Multivariate Logistic regression analysis showed that patient gender,BMI,total propacetamol dosage,liver-related diseases,and concomitant use of hepatic-metabolized antibiotics as independent risk factors for DILI(P<0.05).Conclusion The use of propacetamol for postoperative analgesia presents a risk for liver injury,and the risk is particularly pronounced in males,obesity,high-dose dosing,patients with underlying hepatic disease,and comorbid hepatic metabolism of antimicrobial drug use.It is recommended to strengthen the monitoring of liver function in clinical application,strictly control the dosage and duration of treatment,and avoid co-administration with hepatotoxic drugs to ensure the safety of drug use.

Objective:To investigate the effect of Omaha system interventional management on therapeutic effect and incidence of major adverse cardiovascular events(MACE)during follow-up in patients with heart failure(HF).Methods:This randomized controlled study enrolled 110 HF patients treated in Second Affiliated Hospital of Chi-nese PLA Air Force Military Medical University between January 2021 and January 2023.They were divided into control group(n=55,routine nursing)and intervention group(n=55,interventional management based on Omaha system).Both groups received intervention for 1 month and were followed up for 6 months.The heart function,negative emotion,self-care capacity,quality of life,and cumulative incidence of MACE during the 6-month fol-low-up were compared between two groups.Results:Compared with patients in the control group,those in the in-tervention group had significant higher left ventricular ejection fraction(LVEF)[(60.32±4.79)％vs.(50.11±4.58)％],scores of exercise of self-care agency(ESCA)[(142.33±6.58)points vs.(89.26±7.19)points]and General Quality of Life Inventory 74(GQOLI-74)[(88.61±4.15)points vs.(70.59±7.85)points](P＜0.001 all),and significant lower left atrial diameter(LAD)[(36.18±2.98)mm vs.(40.25±3.05)mm],left ventricu-lar end-systolic diameter(LVESd)[(42.11±3.46)mm vs.(48.49±3.78)mm],scores of hospital anxiety and depression scale[HADS(A)][(10.05±2.11)points vs.(14.33±2.05)points]and HADS(D)[(9.15±1.31)points vs.(13.37±2.18)points](P＜0.001 all).The incidence rate of MACE in intervention group(9.09％vs.29.09％)was significantly lower than that of control group(P=0.004).Conclusion:Omaha system interventional management could significantly improve cardiac function and negative emotions,improve self-care capacity and quality of life,and reduce the incidence of MACE during follow-up in patients with heart failure.

Percutaneous renal denervation(RDN)is a minimally invasive interventional treatment for hypertension that has been used in clinics at home and abroad,primarily for patients with resistant hypertension or who cannot tolerate antihypertensive drugs.Current clinical studies have confirmed the safety and efficacy of this technique.As RDN is still in its promotional and popularization stage,the expert group has written this clinical pathway to promote the orderly implementation of this technology,standardize the operating process,and standardize diagnostic and therapeutic behaviors.The pathway describes the clinical assessment of patients in detail(including indications,contraindications,and the patient screening process),the standardized operating process for RDN(including perioperative medication,anaesthesia,ablation,and management of complications),and the postoperative follow-up plan(including follow-up content,methods,and timing).It is hoped that this will serve as a reference for physicians involved in RDN clinical work,standardize diagnostic and therapeutic behaviors,and promote the standardized,precise,and sustainable development of the RDN discipline.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.