Objective: To investigate the barrier membrane fixation performance and enhanced guided bone regeneration (GBR) capability of a thermosensitive adhesive containing bioactive glass nanoparticles in order to provide a novel solution for membrane fixation during GBR procedures. Methods: M2NP@BGN (methoxyethyl acrylate-co-N-isopropylacrylamide-co-protocatechuic acid@Bioactive glass nanoparticle), a thermosensitive adhesive, was synthesized via free radical polymerization by compositing methoxyethyl acrylate, N-isopropylacrylamide, and protocatechuic acid into a basic adhesive that was modified with bioactive glass nanoparticle (BGN). The successful fabrication of basic adhesive M2NP was characterized by attenuated total reflection-Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The thermosensitive adhesive M2NP@BGN (BGN concentration of 1 mg/mL) was characterized by scanning electron microscopy and a rheometer. By adjusting the BGN concentration (0.1 mg/mL, 0.5 mg/mL, 1 mg/mL, and 2 mg/mL), the adhesive and mechanical strengths were investigated with a universal testing machine. Biocompatibility was evaluated with a cell counting kit-8 assay and hemolysis test to identify the optimal formulation. The optimal material’s extract was co-cultured with mouse bone marrow mesenchymal stem cells, and its osteogenic activity was examined in vitro by quantitative real-time PCR, alkaline phosphatase, and alizarin red S staining. The rat mandibular defect model was established, filled with bone graft, and divided into 3 groups based on membrane fixation method: M2NP@BGN (BGN concentration of 1 mg/mL) fixation group (M2NP@BGN), titanium nail fixation group (Nail), and unfixed control group (Negative). Bone regeneration was analyzed after 8 weeks by micro computed tomography and histological staining. Results: M2NP@BGN (BGN concentration of 1 mg/mL) was successfully synthesized and demonstrated rapid gelation under warm, humid conditions. The adhesive with a BGN concentration of 1 mg/mL exhibited the highest adhesive strength (P < 0.001) and significantly enhanced mechanical strength (P < 0.001) under 37℃ wet conditions. All formulations showed excellent biocompatibility, with cell viability > 80% and hemolysis ratio < 5%. M2NP@BGN (BGN concentration of 1 mg/mL) significantly upregulated the expression of Runx2 and Col I (P < 0.001) and enhanced the activity of osteogenic differentiation markers (P < 0.05). In the animal model, the M2NP@BGN group (BGN concentration of 1 mg/mL) achieved significantly higher bone volume fraction and better bone maturity compared to the negative and nail groups (P < 0.05). Conclusion M2NP@BGN (BGN concentration of 1 mg/mL) combines excellent wet adhesion with potent osteogenic activity, enhances the bone augmentation efficacy of membranes, and presents a novel fixation strategy with significant clinical translation potential for GBR therapy.

ObjectiveBiochemistry and Molecular Biology, a discipline that elucidates life phenomena at the molecular level, serves as a core foundational course in medical education. It provides the theoretical basis for studying other basic and clinical medical subjects, as well as for understanding pathogenesis, disease diagnosis, and treatment. However, its complex content and highly abstract concepts have posed a dual challenge to traditional teaching models: “inefficient instruction” and “inadequate learning outcomes”. Within limited classroom hours, how to engage students and stimulate their intrinsic motivation, and how to help them recognize, understand, and develop a passion for biochemistry from the perspective of the discipline’s essence, have long been key focuses of curriculum research. MethodsUsing the lipid metabolism chapter as an example, this study employs “Rain Classroom”, a generative artificial intelligence (AI)-assisted platform, to support education in four dimensions: teaching, learning, evaluation, and research. In teaching, it assists instructors through virtual experiments, lesson preparation support, knowledge mapping, and assignment design. For learning, it serves as an intelligent study assistant for students, providing automated assignment review, enabling educational resource sharing, and facilitating personalized learning pathways. In evaluation, the platform automates assignment grading, analyzes student performance data, and offers diagnostic feedback and teaching recommendations. In research, it aids educators in collecting and analyzing teaching data, as well as searching for and summarizing relevant literature. ResultsThe results indicate that an educational model integrating teacher-led instruction, student-centered learning, and generative AI assistance significantly enhances teaching quality, students’ self-directed learning abilities, and knowledge mastery. Furthermore, with the support of generative AI, curriculum-based ideological education—focusing on cutting-edge disciplinary advances and topical medical issues—helps cultivate students’ medical spirit of “honoring life and healing the wounded”, thereby fostering the establishment of appropriate professional values. Finally, while generative AI presents both opportunities and challenges for higher education, this study also analyzes potential risks in its teaching applications, emphasizing the need for both instructors and students to avoid over-reliance and to ensure that technological tools consistently serve the fundamental goals of education. ConclusionThis study demonstrates that integrating generative AI, specifically via the “Rain Classroom” platform, can effectively enhance biochemistry education. By supporting teaching, learning, evaluation, and research, this approach improves both educational effectiveness and student outcomes. It also facilitates the incorporation of cutting-edge knowledge and professional ethics, nurturing a patient-centered mindset. Additionally, the study addresses potential implementation risks to ensure that such technological tools remain aligned with the core purpose of education.

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.

ObjectiveTo investigate the changing trends of the incidence rate， prevalence rate， mortality rate， and disability-adjusted life years （DALYs） of benign hepatobiliary and pancreatic diseases among people aged 15 — 39 years in China in 1990 — 2021. MethodsThe data of 2021 Global Burden of Disease Study were downloaded to obtain the epidemiological data of liver fibrosis/chronic liver disease， benign gallbladder/biliary tract diseases， and pancreatitis among people aged 15 — 39 years in China， and estimated annual percentage change （EAPC） was calculated to assess the changing trends of incidence， prevalence， mortality， and DALY rates. The Bayesian age-period-cohort model was used to predict the incidence and mortality rates from 2022 to 2030. ResultsIn 2021， there were 10 448 778 new cases of benign hepatobiliary and pancreatic diseases among the individuals aged 15 — 39 years in China， which was increased by 3.8% compared with the data in 1990， while the numbers of prevalent cases， deaths， and DALYs were reduced by 20.4%， 59.6%， and 50.2%， respectively. In 2021， the age-standardized incidence rates of liver fibrosis/chronic liver disease， benign gallbladder/biliary tract diseases， and pancreatitis were 1 104.40/100 000， 1 045.05/100 000， and 16.64/100 000， respectively； the age-standardized prevalence rates were 20 592.37/100 000， 2 364.85/100 000， and 9.43/100 000， respectively； the age-standardized mortality rates were 1.61/100 000， 0.04/100 000， and 0.18/100 000， respectively. From 1990 to 2021， there was a tendency of increase in the age-standardized incidence rate of liver fibrosis/chronic liver disease （EAPC=0.43， 95% confidence interval ［CI］： 0.23 — 0.63）， and there was also a tendency of increase in the age-standardized incidence and prevalence rates of benign gallbladder/biliary tract diseases （incidence rate： EAPC=1.07， 95%CI： 0.91 — 1.24； prevalence rate： EAPC=0.75， 95%CI： 0.59 — 0.89）， while there was a tendency of reduction in the age-standardized mortality rate of all three disease categories. Predictions for 2022 — 2030 indicated a potential reduction in the incidence rate of benign gallbladder/biliary tract diseases and an increase in the incidence rate of pancreatitis. ConclusionThere has been an overall upward trend in the incidence rate of liver fibrosis/chronic liver disease and gallbladder/biliary tract diseases over the past three decades， and it is needed to pay attention to the disease burden of benign hepatobiliary diseases among the people aged 15 — 39 years in China.

The Pharmacovigilance Guidelines for Clinical Application of Traditional Chinese Medicine Injections （hereinafter referred to as the Guidelines） were released by the China Association of Chinese Medicine， with the standard number T/CACM 1563.4—2024. It is the first specialized guideline in China on the approach to pharmacovigilance activities for the clinical application of traditional Chinese medicine injections （TCMIs）. The Guidelines were jointly developed by the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， along with 30 experts in TCM pharmacovigilance， clinical practice （TCM， as well as integrated traditional Chinese and Western medicine），and evidence-based medicine from across the country. This publication filled the gap in standard documents in this field， both domestically and internationally. The Guidelines were formulated according to GB/T1.1—2020 Directives for standardization—Part 1： Rules for the structure and drafting of standardizing documents， the WHO Handbook for Guideline Development，and other methodological norms. Based on international norms，national laws and regulations，and scientific research results in the field of pharmacovigilance， methods adopted included expert interviews，literature research，nominal group technique， and Delphi method. Then， key points for pharmacovigilance for TCM injections were summarized and clarified in the four critical sections of "monitoring"，"identification"，"assessment"，and "control". The development process of the Guidelines included project initiation， international registration， expert interviews， literature search， and evaluation. Based on the research results of these steps，a draft was formed and revised through multiple rounds of in-group expert discussion and peer evaluations by 56 external experts. After revisions by the working group based on the feedback， the final version was formed. The Guidelines came into effect on January 8，2024，providing suggestions and reference norms for pharmacovigilance in the clinical application of TCMIs. To further promote the application and popularization of the Guidelines and help pharmacovigilance personnel better understand the development process，this study elucidates the background，methodological framework，and key development steps of the Guidelines.

The Pharmacovigilance Guidelines for Clinical Application of Traditional Chinese Medicine Injections （hereinafter referred to as the Guidelines） were released by the China Association of Chinese Medicine， with the standard number T/CACM 1563.4—2024. It is the first specialized guideline in China on the approach to pharmacovigilance activities for the clinical application of traditional Chinese medicine injections （TCMIs）. The Guidelines were jointly developed by the Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences， along with 30 experts in TCM pharmacovigilance， clinical practice （TCM， as well as integrated traditional Chinese and Western medicine），and evidence-based medicine from across the country. This publication filled the gap in standard documents in this field， both domestically and internationally. The Guidelines were formulated according to GB/T1.1—2020 Directives for standardization—Part 1： Rules for the structure and drafting of standardizing documents， the WHO Handbook for Guideline Development，and other methodological norms. Based on international norms，national laws and regulations，and scientific research results in the field of pharmacovigilance， methods adopted included expert interviews，literature research，nominal group technique， and Delphi method. Then， key points for pharmacovigilance for TCM injections were summarized and clarified in the four critical sections of "monitoring"，"identification"，"assessment"，and "control". The development process of the Guidelines included project initiation， international registration， expert interviews， literature search， and evaluation. Based on the research results of these steps，a draft was formed and revised through multiple rounds of in-group expert discussion and peer evaluations by 56 external experts. After revisions by the working group based on the feedback， the final version was formed. The Guidelines came into effect on January 8，2024，providing suggestions and reference norms for pharmacovigilance in the clinical application of TCMIs. To further promote the application and popularization of the Guidelines and help pharmacovigilance personnel better understand the development process，this study elucidates the background，methodological framework，and key development steps of the Guidelines.

ObjectiveTo develop and validate a nomogram based on the albumin-bilirubin （ALBI） score for predicting the risk of severe perioperative complications in patients undergoing hepatectomy for hepatolithiasis. MethodsA retrospective analysis was conducted on the clinical data of 163 hepatolithiasis patients who underwent hepatectomy. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for severe perioperative complications. A nomogram prediction model was constructed and its performance was evaluated. ResultsAmong the 163 patients， 66 and 97 were classified into the low-grade and high-grade ALBI groups， respectively. Significant intergroup differences were observed in gender， total bilirubin， albumin levels， and the incidence of severe complications （P0.05）. Severe complications occurred in 40 patients. Independent risk factors included age 60 years （OR=5.49， P0.001）， high-grade ALBI （OR=8.30， P0.001）， history of biliary surgery （OR=2.60， P=0.035）， hepatectomy （segmentectomy）≥3 （OR=2.75， P=0.028）， and open surgical approach （OR=4.00， P=0.009）. A nomogram for predicting severe perioperative complications was successfully established. Internal validation showed that the model had an area under the ROC curve （AUC） of 0.865， which outperformed traditional single predictors. The calibration curve closely aligned with the ideal curve， with a mean absolute error （MAE） of 0.027. Decision curve analysis （DCA） demonstrated a net clinical benefit when the threshold probability exceeded 10%， superior to that of traditional predictors. ConclusionThe ALBI score-based nomogram is successfully developed and validated to predict the risk of severe perioperative complications in hepatolithiasis patients undergoing hepatectomy. The model demonstrated favorable predictive performance and high clinical utility， serving as an effective tool for both preoperative risk assessment and postoperative risk stratification.

Objective To analyze the clinical efficacy of valve surgeries for infective endocarditis and the affecting factors, and compare the early- and long-term postoperative outcomes of different surgery approaches. Methods The patients with infective endocarditis who underwent valve replacement/valvuloplasty in our hospital from 2010 to 2022 were retrospectively collected. The clinical data of the patients were analyzed. Results A total of 343 patients were enrolled, including 197 patients with mechanical valve replacement, 62 patients with bioprosthetic valve replacement, and 84 patients with valvuloplasty. There were 238 males and 105 females with an average age of (44.2±14.8) years. Single-valve endocarditis was present in 200 (58.3%) patients, and multivalve involvement was present in 143 (41.7%) patients. Sixty (17.5%) patients had suffered thrombosis before surgery, including cerebral embolisms in 32 patients. The mean follow-up time was (60.6±43.8) months. Early mortality within one month after the surgery occurred in 17 (5.0%) patients, while later mortality occurred in 19 (5.5%) patients. Eight (2.3%) patients underwent postoperative dialysis, 13 (3.8%) patients suffered postoperative stroke, 6 patients underwent reoperation, and 3 patients suffered recurrence of infective endocarditis. Smoking (P=0.002), preoperative embolisms (P=0.001), duration of surgery (P=0.001), and postoperative dialysis (P=0.001) were risk factors for early mortality, and left ventricular ejection fraction ≥60% (P=0.022) was protective factor for early mortality. New York Heart Association classification Ⅲ-Ⅳ (P=0.010) and ≥3 valve procedures (P=0.028) were risk factors for late mortality. The rate of composite endpoint events was significantly lower in the valvuloplasty group than that in the valve replacement group. Conclusion For patients with infective endocarditis, smoking and preoperative embolisms are associated with high postoperative mortality, multiple-valve surgery is associated with a poorer prognosis, and valvuloplasty has advantages over valve replacement and should be attempted in the surgical management of patients with infective endocarditis.

Objective: To explore the relationship of physical activity (PA) and sedentary behavior (SB) with cardiorespiratory fitness (CRF) among middle schoold students in Tibet, so as to provide empirical references for improving the cardiorespiratory fitness and health levels of adolescents in Tibet. Methods: From August to December 2020, 1 225 junior and senior high school students were selected from 2 middle schools in Lhasa, Tibet Autonomous Region, using the stratified cluster random sampling method. Triaxial accelerometers were used to evaluate PA and SB behaviors, and the 20 meter shuttle run was employed to assess CRF among the middle school students. Isochronous substitution modeling was used to analyze the associations of SB, low intensity physical activity (LPA), and moderate vigorous physical activity (MVPA) with CRF, and the saturation threshold effect in the dose response relationship between MVPA and CRF was analyzed through restricted cubic spline and two stage linear regression. Results: After adjusting for covariates such as gender, body mass index and sleep quality score, isotemporal substitution analysis showed that among junior high school students aged 13-15, replacing 30 minutes of SB ( B =1.73) or LPA ( B =2.38) with MVPA were positively associated with CRF (both P <0.05). Among senior high school students aged 16-18, replacing SB ( B =0.99) or LPA ( B =1.38) with MVPA were also positively associated with CRF (both P <0.05). Restricted cubic spline and two piecewise linear regression analyses indicated that only middle school girls aged 13-18 exhibited a saturation threshold effect between MVPA and CRF (logarithmic likelihood ratio test=0.03), with the optimal CRF improvement observed at 60 minutes of MVPA per day ( B=0.13, P ＜ 0.01). Conclusions Reducing SB and LPA while increasing MVPA can improve CRF in Tibetan middle school students. To maximize CRF improvement, middle school girls should engage in at least 60 minutes of MVPA daily.

Sleep deprivation (SD) has emerged as a significant modifiable risk factor for Alzheimer’s disease (AD), with mounting evidence demonstrating its multifaceted role in accelerating AD pathogenesis through diverse molecular, cellular, and systemic mechanisms. SD is refined within the broader spectrum of sleep-wake and circadian disruption, emphasizing that both acute total sleep loss and chronic sleep restriction destabilize the homeostatic and circadian processes governing glymphatic clearance of neurotoxic proteins. During normal sleep, concentrations of interstitial Aβ and tau fall as cerebrospinal fluid oscillations flush extracellular waste; SD abolishes this rhythm, causing overnight rises in soluble Aβ and tau species in rodent hippocampus and human CSF. Orexinergic neurons sustain arousal, and become hyperactive under SD, further delaying sleep onset and amplifying Aβ production. At the molecular level, SD disrupts Aβ homeostasis through multiple converging pathways, including enhanced production via beta-site APP cleaving enzyme 1 (BACE1) upregulation, coupled with impaired clearance mechanisms involving the glymphatic system dysfunction and reduced Aβ-degrading enzymes (neprilysin and insulin-degrading enzyme). Cellular and histological analyses revealed that these proteinopathies are significantly exacerbated by SD-induced neuroinflammatory cascades characterized by microglial overactivation, astrocyte reactivity, and sustained elevation of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) through NF‑κB signaling and NLRP3 inflammasome activation, creating a self-perpetuating cycle of neurotoxicity. The synaptic and neuronal consequences of chronic SD are particularly profound and potentially irreversible, featuring reduced expression of critical synaptic markers (PSD95, synaptophysin), impaired long-term potentiation (LTP), dendritic spine loss, and diminished neurotrophic support, especially brain-derived neurotrophic factor (BDNF) depletion, which collectively contribute to progressive cognitive decline and memory deficits. Mechanistic investigations identify three core pathways through which SD exerts its neurodegenerative effects: circadian rhythm disruption via BMAL1 suppression, orexin system hyperactivity leading to sustained wakefulness and metabolic stress, and oxidative stress accumulation through mitochondrial dysfunction and reactive oxygen species overproduction. The review critically evaluates promising therapeutic interventions including pharmacological approaches (melatonin, dual orexin receptor antagonists), metabolic strategies (ketogenic diets, and Mediterranean diets rich in omega-3 fatty acids), lifestyle modifications (targeted exercise regimens, cognitive behavioral therapy for insomnia), and emerging technologies (non-invasive photobiomodulation, transcranial magnetic stimulation). Current research limitations include insufficient understanding of dose-response relationships between SD duration/intensity and AD pathology progression, lack of long-term longitudinal clinical data in genetically vulnerable populations (particularly APOE ε4 carriers and those with familial AD mutations), the absence of standardized SD protocols across experimental models that accurately mimic human chronic sleep restriction patterns, and limited investigation of sex differences in SD-induced AD risk. The accumulated evidence underscores the importance of addressing sleep disturbances as part of multimodal AD prevention strategies and highlights the urgent need for clinical trials evaluating sleep-focused interventions in at-risk populations. The review proposes future directions focused on translating mechanistic insights into precision medicine approaches, emphasizing the need for biomarkers to identify SD-vulnerable individuals, chronotherapeutic strategies aligned with circadian biology, and multi-omics integration across sleep, proteostasis and immune profiles may delineate precision-medicine strategies for at-risk populations. By systematically examining these critical connections, this analysis positions sleep quality optimization as a viable strategy for AD prevention and early intervention while providing a comprehensive roadmap for future mechanistic and interventional research in this rapidly evolving field.