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.

Hepatitis B virus （HBV） is a unique hepatotropic DNA virus that forms covalently closed circular DNA within the nucleus of hepatocytes and can partially integrate into the host genome， establishing the molecular basis for persistent viral infection. HBV infection and replication depends on multiple hepatocyte-enriched host factors and is modulated by the hepatic microenvironment. The host achieves natural control and clearance of HBV through various mechanisms， including cytolytic elimination mediated by cellular immunity such as cytotoxic T lymphocytes and natural killer cells， innate immunity and noncytolytic clearance driven by interferons and various cytokines， and antibody-mediated protection and clearance as part of humoral immune response. In addition， intracellular restriction factors and pathways， hepatocyte turnover through division and replacement， and changes in the hepatic microenvironment （such as the increase in matrix stiffness） collectively influence the efficiency and outcome of viral control and clearance. This article clarifies and elaborates on related mechanisms， so as to deepen the understanding of HBV chronicity， spontaneous resolution， and cure and provide a theoretical basis for optimizing clinical management and developing novel therapeutic strategies.

Osteoporotic fractures(OPF) refer to the fractures caused by minor violence in the state of osteoporosis, seriously threatening the life and health of elderly patients. Drug and surgical therapies have limitations such as single targets, diverse adverse reactions, and poor prognosis. Kidney-tonifying traditional Chinese medicine(TCM) has good potential in the treatment of OPF. TCM can promote the healing of OPF by promoting angiogenesis in the early stage of bone healing, promoting osteogenic differentiation of bone marrow mesenchymal stem cells in the stage of bone repair, maintaining the balance of osteogenic and osteoclastic system in the stage of bone remodeling, and regulating the oxidative stress responses throughout the process of OPF healing. TCM can alleviate the pathological state of osteoporosis and promote fracture healing in OPF patients via multiple pathways and targets, demonstrating the advantages and potential of biphasic regulation.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Osteoporotic Fractures/metabolism* ; Animals ; Fracture Healing/drug effects* ; Medicine, Chinese Traditional ; Kidney/metabolism* ; Osteogenesis/drug effects*

OBJECTIVE: To investigate the risk factors associated with the development of knee osteoarthritis (OA) following arthroscopic surgery for degenerative lesions of the posterior horn of the medial meniscus. METHODS: Between January 2012 and January 2014, a retrospective analysis was conducted on 506 patients who underwent arthroscopic surgery for degenerative disease of the posterior horn of the medial meniscus. The cohort included 230 males and 276 females, aged from 32 to 58 years old with an average of (46.77±9.02) years old. According to the results of postoperative follow-up, patients were categorized into a knee osteoarthritis(OA) group and a non-OA group. The following parameters were recorded for each subject:gender, medial proximal tibial angle (MPTA), hip-knee-ankle angle (HKA), presence of bone edema on MRI, physical characteristics (including McMurray test results, locking symptoms, and medial knee tenderness points), meniscus protrusion, type of meniscus injury, and free body condition as observed via arthroscopy. Multivariate unconditional Logistic regression analysis was employed to investigate the associated factors influencing the 10-year postoperative incidence of knee osteoarthritis following surgery for degenerative injury of the posterior horn of the medial meniscus. Independent risk factors potentially influencing the development of postoperative OA were identified, and a nomogram-based predictive model for postoperative OA was established. The discriminatory ability and calibration accuracy of the model were assessed using the C-index and Hosmer-Lemeshow goodness-of-fit test, respectively. Furthermore, internal validation was performed using the bootstrap resampling method. RESULTS: Within a 10-year period following arthroscopic surgery, there were 123 patients in the OA group and 383 patients in the non-OA group. Significant differences were observed between two groups with respect to gender (χ²=5.156, P=0.023), MPTA<86.6° (χ²=21.671, P<0.001), varus lower limb alignment( χ²= 80.086, P<0.001). Additionally, meniscus extrusion (χ²=6.371, P=0.012), meniscus transverse tear (χ²=14.573, P<0.001), and bone edema detected on MRI(χ²=9.881, P=0.002) were identified as factors associated with the development of postoperative knee OA. The multifactorial Logistic regression analysis revealed that the lower limb line of force inversion OR=4.324, 95%CI (1.391, 13.443), P=0.011;MPTA <86.6°, OR=2.519, 95%CI (1.150, 5.519), P=0.021;transverse meniscus tear, OR=4.546, 95%CI (1.827, 11.310), P=0.001;meniscus ectropion, OR=5.401, 95%CI (1.992, 14.646), P=0.001;and bone edema manifestation on MRI OR=2.692, 95%CI (1.169, 6.200), P=0.020. They were independent risk factors associated with the development of postoperative OA. The area under the ROC curve predicted by the model was 0.927, 95%CI (0.903, 0.950). The Hosmer-Lemeshow goodness-of-fit test, used to evaluate the accuracy of the model, yielded P=0.689. Additionally, the internally sampled calibration curve demonstrated good consistency with the actual postoperative OA outcomes. CONCLUSION Varus alignment of the lower extremity, MPTA <86.6°, transverse meniscus tear, lateral meniscus injury, and bone marrow edema observed on MRI were independent risk factors for the development of knee osteoarthritis following arthroscopic surgery. Additionally, the prognostic model demonstrated excellent predictive performance.
Humans ; Male ; Female ; Middle Aged ; Arthroscopy/adverse effects* ; Adult ; Retrospective Studies ; Tibial Meniscus Injuries/surgery* ; Osteoarthritis, Knee/epidemiology* ; Risk Factors ; Menisci, Tibial/surgery* ; Incidence ; Postoperative Complications/epidemiology*

OBJECTIVE: To investigate the effects of acupuncture on the neurotransmitter levels and gut microbiota in a mouse model of Tourette syndrome (TS). METHODS: Thirty-six male C57/BL6 mice were randomly divided into 4 groups using a random number table method: 3,3'-iminodipropionitrile (IDPN) group, control group, acupuncture group, and tiapride group, with 9 mice in each group. In the IDPN group, acupuncture group, and tiapride group, mice received daily intraperitoneal injections of IDPN (300 mg/kg body weight) for 7 consecutive days to induce stereotyped behaviors. Subsequently, in the acupuncture intervention group, standardized acupuncture treatment was administered for 14 consecutive days to IDPN-induced TS model mice. The selected acupoints included Baihui (DU 20), Yintang (DU 29), Waiguan (SJ 5), and Zulinqi (GB 41). In the tiapride group, mice were administered tiapride (50 mg/kg body weight) via oral gavage daily for 14 consecutive days. The control group, IDPN group, and acupuncture group received the same volume of saline orally for 14 consecutive days. Stereotypic behaviors were quantified through behavioral assessments. Neurotransmitter levels, including dopamine (DA), glutamate (Glu), and aspartate (ASP) in striatal tissue were measured using enzyme-linked immunosorbent assay. Dopamine transporter (DAT) expression levels were additionally quantified through quantitative polymerase chain reaction (qPCR). Gut microbial composition was analyzed through 16S ribosomal RNA gene sequencing, while metabolic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Acupuncture administration significantly attenuated stereotypic behaviors, concurrently reducing striatal levels of DA, Glu and ASP concentrations while upregulating DAT expression compared with untreated TS controls (P<0.05 or P<0.01). Comparative analysis identified significant differences in Muribaculaceae (P=0.001), Oscillospiraceae (P=0.049), Desulfovibrionaceae (P=0.001), and Marinifilaceae (P=0.014) following acupuncture intervention. Metabolomic profiling revealed alterations in 7 metabolites and 18 metabolic pathways when compared to the TS mice, which involved various amino acid metabolisms associated with DA, Glu, and ASP. CONCLUSIONS Acupuncture demonstrates significant modulatory effects on both central neurotransmitter systems and gut microbial ecology, thereby highlighting its dual therapeutic potential for TS management through gut-brain axis regulation.
Animals ; Tourette Syndrome/metabolism* ; Gastrointestinal Microbiome ; Neurotransmitter Agents/metabolism* ; Acupuncture Therapy ; Male ; Mice, Inbred C57BL ; Mice

Objective:To investigate the incidence of shoulder work-related musculoskeletal disorders (WMSDs) among occupational population in China, and to explore their intrinsic association with personal and work-related factors.Methods:In April 2024, 73497 valid questionnaires of the Chinese version of the Musculoskeletal Disorders Electronic Questionnaire were retrospectively analyzed from June 2018 to December 2023 in 22 provinces and 29 key industries in China, and the general information, occurrence of WMSDs and related risk factors of key occupational populations in different regions in China were collected. By using Chi-square test and confirmatory factor analysis, the relationship between shoulder fatigue and pain in key occupational groups and individual factors, work type, work posture and work organization was discussed, and the internal relationship was analyzed based on structural equation model.Results:Higher incidence of shoulder fatigue and pain were associated with female, lack of physical exercise, uncomfortable working posture and neck leaning forward ( P<0.05). Structural equation model analysis showed that work type, work posture and work organization were strongly correlated ( r=0.58, 0.55). Work organization and work type were strongly correlated with shoulder fatigue ( r=0.65) and moderately correlated with shoulder fatigue ( r=0.21). Shoulder fatigue was moderately associated with shoulder pain ( r=0.40). Individual factors, work type, work posture and shoulder fatigue could directly affect shoulder pain ( OR=0.07, -0.09, 0.17 and 0.40), and work type and work posture could also indirectly affect shoulder pain through shoulder fatigue ( OR=0.08, 0.03). Work organization only indirectly affected shoulder pain through shoulder fatigue ( OR=0.26) . Conclusion:The main influencing factor of shoulder pain is shoulder fatigue, followed by work posture and individual factors. Structural equation model can better reflect the complex relationship between work type, work posture and work organization and shoulder WMSDs. Improving work posture and work organization may be an effective way to control the influence of shoulder fatigue on shoulder pain.

Objective:To explore the structural equation model to explore the levels of work-related musculoskeletal disorders (WMSDs) and various risk factors in the feet and ankle of China's occupational population, providing scientific basis for for preventing WMSDs in feet and ankles.Methods:Data of 73497 national occupational epidemiological cases were selected from June 2018 to December 2023 used the Chinese version of the Electronic Questionnaire on Musculoskeletal Disorders. The adverse ergonomic factors and their source classification standard and confirmatory factor analysis were used to investigate foot and ankle WMSDs and their related risk factors (including individual factors, work organization, work posture, work type, fatigue, etc.) in key occupational groups in China, and structural equation model hypothesis, fitting, verification, and path and intermediary effect analysis were carried out. The model fit evaluation indexes included Chi-square specific degrees of freedom ( χ2/ df), gauge fit index (NFI), Tucker Lewis index (TLI), goodness of Fit index (GFI), adjusted Goodness of Fit index (AGFI) and approximate root mean square error (RMSEA) . Results:A total of 73497 occupational workers were surveyed, with local muscle fatigue and WMSDs incidence rates in the feet and ankles being 17.17% and 12.06%, respectively. The fitting index of the adjusted structural equation model basically meets the standard (GFI=1, AGFI=1, RMESA=0.042, NFI=0.716, TLI=0.663). The top three factors affecting feet and ankle WMSDs are feet and ankle muscle fatigue, work type, and work organization, with standardized path coefficients of 0.221, 0.105, and 0.095, respectively. The top two factors affecting feet and ankle muscle fatigue are work organization and work type, with standardized path coefficients of 0.548 and 0.383, respectively. Feet and ankle muscle fatigue, work type, work organization, and work posture have a direct effect on feet and ankle WMSDs, with effect values of 0.221, 0.105, 0.095, and 0.077, respectively. The organization and type of work can also have indirect effects through feet and ankle muscle fatigue, with effect values of 0.121 and 0.084, respectively.Conclusion:Feet and ankle muscle fatigue has a direct impact on WMSDs, and plays a mediating role between ankle and ankle WMSDs caused by work organization and work type. Feet and ankle muscle fatigue is an important pathway leading to feet and ankle WMSDs. It is recommended that employers and managers detect job fatigue early and take corresponding prevention and intervention measures, which can play a key role in preventing feet and ankle WMSDs.

Objective:To explore the structural relationship between WMSDs in the upper limbs and various risk factors in the occupational population in China, based on a large sample epidemiological survey and structural equation analysis, and to establish a structural equation model, so as to lay a foundation for the prevention and control of such diseases.Methods:The Chinese version of the Musculoskeletal Disorders Electronic Questionnaire was used to conduct a nationwide survey on the prevalence of WMSDs in the upper extremity. Six factors related to WMSDs in the upper extremity were extracted by the classification standard of adverse ergonomic factors and their source and confirmatory factor analysis, including work organization, work type, upper extremity work posture, individual factors, upper extremity fatigue and upper extremity WMSDs. The structural equation analysis was carried out and the structural equation model was established.Results:The incidence of WMSDs and fatigue in the upper limbs was 24.44% and 43.76%, respectively. The adjusted structural equation model fitting indicators were generally up to the standard (GFI=1.000, AGFI=1.000, RMSEA=0.043, NFI=0.808, TLI=0.784) . The four exogenous latent variables of work organization, work type, upper limb work posture and individual factors were correlated. There was a strong positive correlation between job type and upper limb work posture ( r=0.865) , a moderate positive correlation between work organization and job type and upper limb work posture ( r=0.570, 0.490) , and a weak negative correlation between individual factors and the other three exogenous latent variables. Upper limb work posture and individual factors had direct effects on upper limb WMSDs, and the effect coefficients were 0.10 and 0.06, respectively. Upper limb fatigue played a mediating role between work organization, work type, upper limb work posture and upper limb WMSDs. The effect coefficient was 0.46, and the composition ratios of indirect effects were 100.0%, 100.0%, and 38.3%, respectively. The direct path effect of upper limb work posture, individual factors and upper limb WMSDs was weaker than the mediating path through upper limb fatigue. Conclusion:When carrying out the prevention and control of upper limbWMSDs, it is necessary to comprehensively consider the pathogenesis path of upper limb muscle fatigue and upper limb WMSDs caused by work organization, work type, and upper limb work posture, so as to provide theoretical reference for improving the prevention and control level of such diseases.

Objective To investigate the application of flipped classroom combined with teaching film-reading model in the teaching of filamentous fungal morphology for refresher doctors and evaluate its effect.Methods Fifteen refresher doctors taking microbiology from the 2022 batch of Guangdong Provincial People's Hospital were selected as the control group,and fifteen from the 2023 batch were se-lected as the experimental group.The"Morphological identification of Aspergillus and Mucor" was selected as the teaching content.The experimental group adopted flipped classroom combined with teaching film-reading model for teaching and the control group adopted tra-ditional teaching mode.The theoretical scores,operational scores,film-reading scores,and total scores of the two groups before and af-ter the implementation of teaching were compared and the teaching effect of the experimental group was evaluated using the Question-naire Star.Results The median scores of operational,film-reading,and total scores in the experimental group and control group were 40,30,and 95.5 and 36,27,and 85.5,respectively,and all the three scores in the experimental group were significantly higher than those in the control group(P＜0.05).Conclusion The flipped classroom combined with teaching film-reading model helps to improve the teaching effect of filamentous fungal morphology for refresher doctors,with high satisfaction,and can provide reference for subse-quent filamentous fungal morphology teaching.