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.

Chronic heart failure （CHF） is an end-stage cardiac syndrome driven by multiple factors. Its pathological process involves interactions of multiple pathways such as energy metabolism dysfunction， neuroendocrine dysregulation， and myocardial fibrosis. Although current clinical medicine can alleviate symptoms through single-target approaches， significant limitations in reversing cardiac remodeling and disease progression remain. Puerarin， a major bioactive isoflavone constituent derived from Pueraria lobata， exhibits multidimensional pharmacological effects， such as vasodilatory effects， regulation of neuroendocrine balance， enhancement of metabolic homeostasis， and suppression of myocardial apoptosis. This review systematically integrated puerarin's multi-target regulatory network， elucidating its mechanisms such as improving energy metabolism by AMP-activated protein kinase/mechanistic target of rapamycin （AMPK/mTOR） pathway， inhibiting fibrosis mediated by transforming growth factor-β （TGF-β）/Smad signals， and attenuating oxidative-inflammatory cascades by regulating nuclear factor erythroid 2 （E₂）-related factor 2/nuclear transcription factor-κB（Nrf2/NF-κB） axis. Clinical research data was used to validate its efficacy in improving the left ventricular ejection function and reducing the therapeutic potential of cardiovascular events' risks. The study proposed that puerarin's "systemic regulation" characteristic breaks through the limitations of traditional single-target drugs and prospected its clinical translation pathway based on metabolomics and nano-delivery technology， offering an integrative perspective from molecular mechanisms to precise therapy for the research on modernization of traditional Chinese medicine.

Chronic heart failure （CHF） is an end-stage cardiac syndrome driven by multiple factors. Its pathological process involves interactions of multiple pathways such as energy metabolism dysfunction， neuroendocrine dysregulation， and myocardial fibrosis. Although current clinical medicine can alleviate symptoms through single-target approaches， significant limitations in reversing cardiac remodeling and disease progression remain. Puerarin， a major bioactive isoflavone constituent derived from Pueraria lobata， exhibits multidimensional pharmacological effects， such as vasodilatory effects， regulation of neuroendocrine balance， enhancement of metabolic homeostasis， and suppression of myocardial apoptosis. This review systematically integrated puerarin's multi-target regulatory network， elucidating its mechanisms such as improving energy metabolism by AMP-activated protein kinase/mechanistic target of rapamycin （AMPK/mTOR） pathway， inhibiting fibrosis mediated by transforming growth factor-β （TGF-β）/Smad signals， and attenuating oxidative-inflammatory cascades by regulating nuclear factor erythroid 2 （E₂）-related factor 2/nuclear transcription factor-κB（Nrf2/NF-κB） axis. Clinical research data was used to validate its efficacy in improving the left ventricular ejection function and reducing the therapeutic potential of cardiovascular events' risks. The study proposed that puerarin's "systemic regulation" characteristic breaks through the limitations of traditional single-target drugs and prospected its clinical translation pathway based on metabolomics and nano-delivery technology， offering an integrative perspective from molecular mechanisms to precise therapy for the research on modernization of traditional Chinese medicine.

Objective To establish a stable and reliable sepsis model of rat after liver transplantation (LT) for clinical translational research and analyze its characteristics. Methods The "two-sleeve method" was used to establish the in situ LT model of SD rats, and the sepsis model was constructed through cecal ligation and puncture (CLP) at 3 d after the operation. SD rats were randomly divided into 3 groups: sham operation group (Sham group), LT group, and LT + CLP group, with 6 rats in each group. The changes in body weight, rectal temperature and survival rate were compared, and the sepsis score was used for evaluation. The levels of blood biochemical indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (Urea), creatinine (Cr), creatine kinase (CK), lactate dehydrogenase (LDH)] and inflammatory factors [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α] in each group were detected, and the pathological changes and cell apoptosis in different organs were observed. Results Compared with the Sham group, the body weight of the LT group and LT + CLP group decreased (all P<0.05). The rectal temperature of the LT + CLP group showed a continuous downward trend after the operation, the sepsis score increased sharply after the operation, and the survival rate dropped to 16.7%, and the differences between the Sham group, LT group and LT + CLP group were statistically significant (all P<0.05). The levels of ALT, AST, Urea, Cr, CK, LDH, and serum IL-1β, IL-6, IL-10 and TNF-α in the LT + CLP group were higher than those in the Sham group and LT group rats within 72 hours after the operation(all P<0.05). The pathological examination of the LT + CLP group showed severe tissue structure destruction, necrosis and infiltration of inflammatory cells in multiple organs, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed an increased level of cell apoptosis in multiple organs. Conclusions Using liver transplantation combined with CLP, a stable animal model of liver transplantation infection is successfully established, which exhibits a high mortality rate, significant multi-organ damage and intense inflammatory response, providing an ideal animal model for transplantation infection research.

In response to the clinical needs of cancer treatment and rehabilitation, Professor Lin Hongsheng proposed the Wuzhi Wuyang (five treatments and rehabilitation) concept on the basis of years of clinical experience and the Guben Qingyuan (consolidate the foundation and clear the source) theory. Wuzhi Wuyang emphasizes the importance of treatment and rehabilitation and aims to provide personalized and stage-specific treatment and rehabilitation plans by integrating the advantages of traditional Chinese medicine (TCM) and modern medicine to achieve comprehensive life-cycle management for patients with cancer. The proposal of Wuzhi Wuyang has provided new ideas and methods for the treatment, prevention, and rehabilitation of cancer, along with valuable references for clinical practice and academic research. This article summarizes the connotation of Wuzhi Wuyang and its application in the comprehensive management of cancer prevention and treatment with TCM.

In 2022， Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%， a diagnostic rate of 90%， and a treatment rate of 80% among people aged 18 years and above by the year 2025， and the main intervention measures include population-based prevention， case screening， antiviral therapy， and health management. As of December 31， 2024， a total of 6.875 million individuals in the general population had been screened for hepatitis B， with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified， among whom 156 772 were diagnosed through serological reexamination， resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified， among whom 42 921 had hepatitis B-specific health records established for health management， with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy， with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened， among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing， resulting in a diagnostic rate of 79.2%， and 1 824 individuals with positive HCV RNA were identified， among whom 1 194 received antiviral therapy， with a treatment rate of 65.5%. In addition， 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis， a large number of hepatitis patients have been identified， treated， and managed in the province within a short period of time， which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.

Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM₁, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Objective:To evaluate the efficacy and safety of intrasaccular flow disruptor in wide-necked intracranial aneurysms.Methods:One hundred and seventeen patients with wide-necked intracranial aneurysms treated with intrasaccular flow disruptor were collected from Department of Neurointervention (First Affiliated Hospital of Zhengzhou University), Department of Neurosurgery (Beijing Tiantan Hospital, Capital Medical University), Department of Cerebrovascular Surgery, Neurosurgery Center (Zhujiang Hospital, Southern Medical University), and Department of Neurosurgery (First Affiliated Hospital of Harbin Medical University) from August 2022 to March 2024. Raymond-Roy Occlusion Classification (RROC) was employed to evaluate aneurysm embolization immediately after procedure; cranial CT or MRI within 48 hours of embolization were performed to identify any new intracranial hemorrhage, subarachnoid hemorrhage, or new symptomatic cerebral infarction related to the intracranial aneurysms. Modified Rankin Scale (mRS) was used to assess the neurological function at discharge. Imaging follow-up and outpatient follow-up were performed at 6 months after embolization to evaluate the aneurysm occlusion degree and complications.Results:A total of 117 intrasaccular flow disruptors were implanted in 117 patients, with a technical success rate of 100%; 115 patients (98.3%) enjoyed successful one-time release of their disruptors, and 2 patients (1.7%) required retrieval and redirection of the disruptors before second successful attempt. Flow disruptor plus stent was performed in 13 patients (11.1%). Immediately after procedure, RROC grading I was noted in 3 patients, grading II in 51 patients and grading III in 63 patients. Cranial CT or MRI within 48 hours of embolization indicated no new intracranial hemorrhage, subarachnoid hemorrhage, or symptomatic cerebral infarction related to the intracranial aneurysms. All patients had mRS score of 0 at discharge. Eighty-three patients completed a 6-month follow-up (RROC grading I in 41 patients, grading II in 33 patients and grading III in 9 patients), without ischemic or hemorrhagic adverse events.Conclusion:The results of this study preliminarily suggest that intrasaccular flow disruptor is effective and safe in wide-necked intracranial aneurysms.

Objective:To evaluate the efficacy and safety of Neuroform Atlas stent-assisted coil embolization in patients with middle cerebral artery bifurcation aneurysms.Methods:A retrospective analysis was performed; the clinical data of 46 patients with middle cerebral artery bifurcation aneurysms accepted Neuroform Atlas stent-assisted coil embolization in First Affiliated Hospital of Zhengzhou University, Beijing Tiantan Hospital Affiliated to Capital Medical University, First Affiliated Hospital of Harbin Medical University, Zhujiang Hospital of Southern Medical University and First Affiliated Hospital of Chongqing Medical University from January 2022 to March 2024 were collected. There were 28 ruptured aneurysms (60.87%) and 18 unruptured aneurysms (39.13%). Follow-up was performed for more than 3 months; Raymond-Roy grading was used to evaluate the aneurysm embolization immediately after embolization and during follow-up; perioperative hemorrhagic or ischemic complications were recorded; modified Rankin Scale (mRS) was used to evaluate the prognosis of the patients at discharge and during follow-up (mRS score≤2: good prognosis, and mRS score>2: poor prognosis).Results:Coil embolization was successful in all 46 patients. DSA immediately after embolization showed that 41 patients (89.13%) had completely occluded aneurysms (Raymond-Roy grading I), 2 patients (4.35%) had residual aneurysm neck (Raymond-Roy grading Ⅱ) and 3 patients (6.52%) had partially occluded aneurysms (Raymond-Roy grading Ⅲ). Perioperative complications occurred in 5 patients, including 2 with postoperative cerebral infarction, 1 with hydrocephalus, 1 with postoperative pneumonia leading to respiratory failure, and 1 with stent thrombosis during embolization. Both at discharge and 3 months after embolization, 43 patients (93.48%) had good prognosis and 3 patients (6.52%) had poor prognosis. No obvious ischemic complications (such as stent restenosis) or hemorrhagic complications (such as re-rupture of the aneurysms) were found in all patients. Thirty patients (65.22%) had imaging follow-up for 6-12 months: 26 (86.67%) had Raymond-Roy grading I, 3 (10.00%) had Raymond-Roy grading II, and 1 (3.33%) had Raymond-Roy grading III.Conclusion:Neuroform Atlas stent-assisted coil embolization has good short-term efficacy and high safety in middle cerebral artery bifurcation aneurysms, but long-term follow-up observation is still needed to verify its efficacy.