OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Flap transplantation is a critical surgical strategy for the reconstruction of tissue defects caused by trauma, tumor resection, and congenital malformations, and its survival rate directly determines surgical efficacy and patient prognosis. Following transplantation, flaps inevitably undergo ischemia-reperfusion (I/R) injury, during which oxidative stress, inflammatory responses, and metabolic disturbances are intricately intertwined, ultimately leading to cellular injury and tissue necrosis. Recent studies have demonstrated that multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, necroptosis, and PANoptosis—play central roles in flap I/R injury. The extensive crosstalk and molecular interactions among these pathways form a highly complex cell death network. Specifically, apoptosis is mediated by the imbalance of Bcl-2 family proteins and the activation of cysteine-dependent aspartate-specific protease (caspase) cascades; pyroptosis is driven by the NLRP3-caspase-1-GSDMD axis, resulting in membrane pore formation and the release of pro-inflammatory cytokines; ferroptosis is characterized by iron-dependent lipid peroxidation and dysfunction of glutathione peroxidase 4 (GPX4); necroptosis is triggered by the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3-MLKL signaling complex, leading to membrane rupture; and PANoptosis represents an integrated form of inflammatory cell death that coordinates multiple death pathways. Importantly, these forms of programmed cell death are not independent but are interconnected through extensive signaling crosstalk. Key regulatory molecules, including caspase-8, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), collectively modulate the dynamic balance among these pathways. Therefore, the multidimensional interplay and spatiotemporal dynamics of programmed cell death constitute a fundamental pathological basis of flap I/R injury. This review systematically summarizes the latest advances in the mechanisms and interactions of various programmed cell death pathways in flap I/R injury, aiming to elucidate the underlying regulatory network. These insights may provide novel theoretical foundations for optimizing flap protection strategies, improving flap survival, and promoting tissue repair.

According to traditional Chinese medicine （TCM） theory， impaired spleen transportation function disrupts nutrient distribution， causing metabolic accumulation of lipids that transform into pathogenic phlegm-dampness. These pathological factors disseminate through the San Jiao and obstruct meridian pathways， ultimately forming the pathogenesis described as "all disorders involve phlegm". Phlegm and dampness share common pathogenic origins but manifest distinct clinical manifestations. Dampness， as the precursor， may congeal into phlegm， while existing phlegm accumulation can further exacerbate dampness stagnation， thereby establishing a self-perpetuating pathological cycle. Modern medical research has confirmed that the essence of "phlegm-dampness" syndrome is closely associated with energy metabolism disorders， serving as a common pathological basis for metabolic syndrome， type 2 diabetes mellitus， atherosclerosis， and other major chronic diseases. As a crucial vehicle for medical experimental research， disease-syndrome combination animal models serve as an indispensable means to advance the modernization of TCM. Currently， based on classical theories such as "rich and greasy foods produce phlegm" and "physical coldness combined with cold consumption causes external pathogens to invade the skin and hair， thereby generating internal dampness"， researchers primarily employ two paradigms to construct animal models of phlegm-turbidity， dampness obstruction， and phlegm-dampness syndromes： the first involves simulating TCM etiological factors （through methods like dietary irregularities， imblanace between work and rest， and combined internal-external dampness exposure）， while the second combines disease with syndrome differentiation （inducing pathological changes through physical， chemical， or biological interventions）. Through comprehensive evaluation incorporating macroscopic observation and microscopic index detection， model animals undergo systematic biological and pathological assessment， with further syndrome type verification achieved via the "prescription-based syndrome detection" approach. However， existing models still exhibit significant deficiencies in both the standardization of modeling methodologies and the systematization of evaluation criteria. This paper reviews the strategies for constructing "phlegm-dampness" syndrome animal models and their corresponding evaluation indices， focusing on the pathological correlations among different modeling approaches. The aim is to provide methodological guidance for research on TCM syndromes related to "phlegm-dampness" syndrome and to support the development of TCM therapies for resolving phlegm and eliminating dampness. This study not only contributes to advancing the standardization of TCM syndrome research but also provides crucial technical support for the modernization of TCM.

The female reproductive system is essential for sustaining reproductive endocrine homeostasis,however,its vulnerability to various endogenous and exogenous insults,including pathological conditions,pharmacological agents,genetic predispositions,and environmental factors,often results in compromised fertility.The existing protective approaches(including surgical interventions,hormonal replacement therapies,and assisted reproductive techniques)are constrained by several limitations,such as adverse therapeutic effects,technical complexities,and their incapacity to reverse ovarian senescence.Artemisinin and its derivatives(ARTs),characterized by their unique endoperoxide bridge configuration,have exhibited outstanding therapeutic performance across multiple domains including malaria treatment,anticancer therapy,inflammation modulation,and parasitic infection control.Emerging research has identified their novel protective capabilities against various reproductive system pathologies.This comprehensive review systematically elucidates the molecular mechanisms underlying artemisinin-based interventions in reproductive pathologies and evaluates their clinical translation prospects,thereby proposing innovative strategies for the development of next-generation fertility-protective agents with enhanced safety and efficacy profiles.

Cholangiocarcinoma,as a malignant tumor with strong invasiveness and poor prognosis,has a complex metastasis mechanism,and urgently needs in-depth research.Circulating tumor cells(CTC),as the key cell type for tumor cells to shed from the primary site and enter the bloodstream,have significant research significance.In recent years,studies have found that the invasive pseudopodia of CTC play a significant role in the migration and invasion of tumor cells.Among them,in terms of signal transduction pathways,the Rho family GTPases(RhoA,Rac1,Cdc42)work in coordination to regulate the contractility of the pseudofoot,the branching polymerization and orientation of actin,and the phosphoinositide3-kinase/protein kinase B(PI3K/AKT)pathway promotes the assembly of actin and cross-communicates with the Rho family by activating AKT.At the molecular mechanism level,long non-coding RNAs regulate the expression of pseudopolypod-related genes by adsorbing miRNAs and other means.Matrix metalloproteinase(MMP)degrades the extracellular matrix(ECM)to form an invasion positive feedback.In terms of the microenvironment,cancer-associated fibroblast(CAF)and the cytokines such as transforming growth factor-β(TGF-β)secreted by macrophages,epidermal growth factor(EGF),and interleukin-6(IL-6)activate pseudopodia to form signal transduction pathways.ECM hardness and fiber arrangement affect the extension direction of pseudopodia through mechanical force conduction.This article conducted a comprehensive analysis of the biological characteristics of CTC,the formation mechanism of invasive pseudopodia in cholangiocarcinoma,the metastatic features of cholangiocarcinoma cells and their clinical significance,as well as the role of CTC in the metastatic process of cholangiocarcinoma,in order to summarize the existing research results,explore potential therapeutic targets and future research directions,and provide new ideas for the clinical treatment of cholangiocarcinoma.

Designation of ideological and political teaching of Medical Immunology courses focuses on"cultivate talent for Party and the State",and adheres to goal of"build morality and cultivate people".From perspective of big ideology and politics,with basic foundation of"major guiding,disciplines supporting and curriculum shaping",principle of"six combinations"is applied to con-struct ideological and political cases of Medical Immunology courses,to create an infiltrating teaching pattern,which simultaneously cultivate talent for the Party and the State,and forms a synergistic effect of professional course learning and ideological and political learning.

Objective:To investigate the predictive value of different obesity indicators for colorectal cancer (CRC) risk in different gender populations.Methods:This observational study was conducted within the Kailuan Study (Registration Number: ChiCTR-TNC-11001489). From July 2006 to October 2007, a total of 101,510 employed and retired individuals underwent health examinations, including gastrointestinal disease screening, hematological tests, and questionnaires, at Kailuan General Hospital and its 10 affiliated hospitals. After excluding those with incomplete data, 93,606 participants were included in this study and divided into male (74 852) and female (18 754) groups. CRC incidence was collected through physical examinations and questionnaires every two years. Each participant's follow-up period began at the time of the questionnaire and ended upon CRC diagnosis, death, or December 31, 2021. Body Mass Index (BMI), waist circumference, waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were quartiled (Q1, Q2, Q3, Q4), with Q1 serving as the control group. After adjusting for traditional risk factors such as age, total cholesterol, triglycerides, diabetes, hypertension, smoking status, alcohol consumption, and physical exercise, Cox regression models were used to calculate the correlations between BMI, waist circumference, WHR, WHtR, and CRC incidence in both male and female populations.Results:The age of all patients was (51±12) years, BMI was (25.06±3.49) kg/m 2, waist circumference was (86.94±9.97) cm, hip circumference was (97.30±8.81) cm, WHR was 0.89±0.07, and WHtR was 0.52±0.06.Female participants had significantly lower BMI, waist circumference, WHR, and WHtR compared to males, with statistically significant differences (all P<0.05). The mean follow-up duration for all participants was 15.01 (14.10±2.66) years, during which 718 CRC cases were identified, including 626 males (0.83%) and 92 females (0.49%). Cox proportional hazards models for males showed that CRC risk increased with waist circumference from Q3 (HR=1.43, 95%CI: 1.13-1.79, P=0.003) to Q4 (HR=1.45,95%CI: 1.14-1.82, P=0.002). Similarly, CRC risk increased with WHR from Q3 (HR=1.22, 95%CI: 1.01-1.53, P=0.007) to Q4 (HR=1.43, 95%CI: 1.14-1.79, P=0.002) and with WHtR from Q3 (HR=1.37, 95%CI: 1.08-1.74, P=0.009) to Q4 (HR=1.68, 95%CI: 1.33-2.12, P<0.001). For females, CRC risk increased with waist circumference from Q2 (HR=2.37, 95%CI: 1.20-4.67, P=0.012) to Q3 (HR=2.42, 95%CI: 1.21-4.84, P=0.013) but decreased in Q4 ( HR=2.08, 95%CI: 1.02-4.25, P=0.043). CRC risk increased significantly with WHR from Q2 (HR=2.20, 95%CI: 1.11-4.39, P=0.024) to Q3 (HR=2.89, 95%CI: 1.48-5.67, P=0.002) in females but was not statistically significant in Q4 ( P=0.074). Among females, CRC risk also increased significantly with WHtR in Q2 (HR=2.30, 95% CI: 1.16-4.56, P=0.017) and Q4 (HR=2.64, 95%CI: 1.32-5.29, P=0.006). There were no statistically significant differences in CRC risk associated with BMI in either male or female populations (both P>0.05). Conclusion:Waist circumference, WHR, and WHtR were better predictors of CRC risk than BMI in both male and female populations.

Objective To develop a reminiscence therapy program with Montessori educational philosophy in treatment of elderly people with mild cognitive impairment(MCI)in nursing homes and evaluate its effect.Methods On the basis of Montessori education principles,a reminiscence therapy program was drafted through literature review and had it finalised with expert consultations and a pilot study.Between February and May 2022,70 elderly with MCI were recruited from a nursing home in Liaoning Province using convenience sampling.The recruited elderly were randomly divided into a control group(n=35)and an intervention group(n=35)using a random number table.The elderly in control group received conventional cognitive training only while the elderly in the intervention group received reminiscence therapy in addition to the conventional cognitive training.Cognitive function and ability of daily living(ADL)were compared between the two groups after a 6-week intervention.Results The elderly in intervention group demonstrated statistically significant improvements in both cognitive function and dimensions(visuospatial/executive function,naming ability,delayed recall and orientation,as well as in ADL after a 6-week intervention(all P<0.05).Conclusion The Montessori philosophy based on reminiscence therapy improves cognitive function and activities of daily living in the elderly with MCI,particularly from the perspectives of visuospatial/executive function,naming ability,delayed recall and orientation.

Objective This study sought to accelerate the establishment of a Parkinson's disease mouse model by intracerebral injection of α-synuclein preformed fibrils(α-Syn PFF)into B6-hSNCA-A53T transgenic mice to induce rapid development of Parkinson's-like pathological features.Methods C57BL/6J background α-Syn A53T transgenic mice were selected as the model group,with isogenic C57BL/6J mice as the control group.α-Syn PFF was delivered into the bilateral striatum using stereotactic brain injection.After modeling,the open-field test was used to assess spontaneous activity and anxiety-like behaviors,while the rotarod,grip strength,and pole tests evaluated motor coordination and limb muscle tone.The buried food test was conducted to assess olfactory function.Immunohistochemical staining was performed to investigate neuroinflammation and pathological α-synuclein in the mouse brain.Results Compared with the control group,1 month after the α-Syn PFF injection,model mice showed increased locomotion in the open-field test,with no significant differences in the rotarod,grip strength,or pole tests,but prolonged food-seeking time.Two months after model establishment,the model group showed significantly reduced locomotor activity in open field testing,impaired motor coordination in rotarod,grip strength and pole tests,and olfactory dysfunction in buried food tests.Phosphorylated α-synuclein accumulation was observed in the substantia nigra,cortex,and hippocampus,accompanied by pronounced microglial activation,Lewy body deposition,and substantial dopaminergic neuron loss in the substantia nigra.Conclusions A53T mice developed olfactory dysfunction and motor impairments more rapidly after α-Syn PFF injection.Significant pathological changes were observed,including the aggregation of α-synuclein/Lewy body in the substantia nigra,cortex,and hippocampus,and the loss of dopaminergic neurons in the substantia nigra.This model can serve as a rapidly established animal model for α-synucleinopathy-related Parkinson's disease.