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 therapeutic efficacy of Danggui Shaoyaosan （DSS） on renal injury in db/db mice and its impact on endoplasmic reticulum stress （ERS） in renal tissues. MethodsThirty 8-week-old male db/db mice and six db/m mice were acclimated for one week， after which urinary microalbumin and blood glucose levels were monitored to establish a diabetic kidney disease （DKD） model. The model mice were randomly divided into a model group， an irbesartan group， and three DSS treatment groups with different doses （16.77， 33.54， and 67.08 g·kg^-1·d^-1）. A normal group was set as control. Each group was intragastrically administered with the corresponding drugs or saline for 8 weeks. After the intervention， general conditions were observed. Serum cystatin C （Cys-C）， 24-hour urinary total protein （24 h-UTP）， 24-hour urinary microalbumin （24 h-UMA）， urinary creatinine （Ucr）， and urea nitrogen （UUN） were measured. Transmission electron microscopy （TEM） was used to observe glomerular basement membrane （GBM） and ultrastructural changes of the endoplasmic reticulum （ER） in glomerular endothelial cells. Western blot， real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and immunohistochemistry were used to analyze renal tissue structure and the expression of GRP78， CHOP， and related markers. ResultsCompared with the normal group， the mice in the model group showed curled posture， sluggish response， poor fur condition， increased levels of Cys-C， 24 h-UTP， 24 h-UMA， and UUN （P<0.05）， while Ucr decreased （P<0.05）. The GBM was significantly thickened， with podocyte and foot process fusion. The protein expressions of GRP78， CHOP， and ATF6 were significantly upregulated （P<0.05）， the mRNA levels of GRP78 and CHOP increased （P<0.05）， and immunohistochemistry showed an enhanced GRP78 signal （P<0.05）. After treatment， the mice exhibited improved behavior， normalized GBM and podocyte structure， improved ER morphology and markedly better biochemical indicators. Western blot， Real-time PCR， and immunohistochemistry indicated that the ERS-related markers were downregulated in the DSS treatment groups （P<0.05）， suggesting alleviated ERS and improved renal function. ConclusionDSS can effectively ameliorate renal pathological damage in db/db mice， possibly by regulating ERS in glomerular endothelial cells， although the underlying signaling mechanisms require further investigation.

Objective To explore research hotspots and future development trends in radioactive iodine refractory differentiated thyroid carcinoma (RAIR-DTC) treatment from 2004 to 2024. Methods Literature on RAIR-DTC treatment published from January 2004 to May 2024 was retrieved from the Web of Science (WOS) database. CiteSpace, VOSviewer, and Microsoft Office Excel were used for visual analysis of publication volume, countries, institutions, authors, keywords, and co-citation networks. Results A total of 677 articles were included in the analysis. National and institutional co-occurrence analysis revealed that the United States, along with the MD Anderson Cancer Center at the University of Texas, was the most productive and influential in this field. Author and citation co-occurrence analysis highlighted the substantial contributions of Schlumberger M and Brose MS to the field. The exploration of high-frequency keywords and keyword clustering indicated tyrosine kinase inhibitors and disease prognostic factors were current research hotspots. Keyword burst analysis suggested that future research trends would focus on optimizing clinical benefits through reliable data provided from high-quality clinical trials and achieving personalized, precise treatment management. Conclusion Targeted drugs hold remarkable potential for RAIR-DTC treatment, and emphasizing predictive factors for disease prognosis offers valuable guidance for medical practice.

Objective To establish a chronic rejection (CR) model of mouse heart transplantation and analyze its characteristics. Methods Allogeneic BALB/c and C57BL/6 mice were used as donor and recipient for heart transplantation, and intraperitoneal injection of cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4-Ig) was given 1 and 2 days after surgery. Graft survival time, donor specific antibody (DSA) level, graft pathology and inflammatory cell infiltration were observed. Results In allogeneic transplantation model, graft survival time was prolonged after CTLA4-Ig treatment [(28.2±4.1) d vs. (7.0±0.7) d, P < 0.01]. The level of serum DSA-IgG increased at 2, 3 and 4 weeks after surgery, while the level of DSA-IgM remained unchanged. Myocardial cell injury, inflammatory cell infiltration, interstitial fibrosis and C4d deposition in capillaries were aggravated 3 weeks after operation and worsened 4 weeks after operation. The infiltrated immune cells were mainly macrophages, T cells and plasma cells. Conclusions Mouse allogeneic heart transplantation combined with CTLA4-Ig successfully establishes a CR model, which provides a basis for subsequent studies on the pathogenesis and intervention of CR.

OBJECTIVE To provide technical support for improving recognition rate of adverse drug events （ADEs） related to traditional Chinese medicine （TCM） formula granules and decoction pieces among inpatient patients. METHODS By referencing the global trigger tool （GTT） whitepaper， literature on adverse reactions to TCM， and expert review opinions， ADE trigger items for TCM formula granules and decoction pieces used in the inpatients were established. GTT was applied to analyze ADEs in inpatients who had used TCM formula granules and decoction pieces in our hospital from August 2013 to August 2023， utilizing the Chinese Hospital Pharmacovigilance System. The effectiveness of GTT and the characteristics of these ADEs were analyzed. RESULTS A total of forty-eight triggers were established， including thirty-two laboratory test indexes， thirteen clinical symptoms， and three antidotes. Among the 1 682 patients included， GTT identified 652 potential ADEs， 284 true positive ADEs，with a trigger rate of 38.76% and a positive predictive value of 43.56%. After review by the auditor， 278 cases of ADEs were finally confirmed， with an incidence rate of 16.53%， significantly higher than the number of spontaneously reported ADEs during the same period （0）. The 278 cases of ADEs were mostly grade 1 （223 cases）， mainly involving hepatobiliary system， gastrointestinal system， blood- lymphatic system， etc；a total of 219 types of TCMs are involved，and the top five suspected TCMs used at a frequency higher than 1% were Poria cocos， Codonopsis pilosula， Atractylodes macrocephala， fried Glycyrrhiza uralensis， and Scutellaria baicalensis. CONCLUSIONS The established GTT can improve the recognition rate of ADEs for hospitalized patients using traditional Chinese medicine formula granules and decoction pieces.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Background: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies. Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function. Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores. Conclusion Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Ischemia reperfusion injury （IRI） is often accompanied by serious clinical manifestations， including myocardial hibernation， acute heart failure， brain dysfunction， kidney dysfunction， gastrointestinal dysfunction， liver transplant rejection， systemic inflammatory response syndrome， multiple organ dysfunction syndrome， and so on， which pose important treatment challenges for doctors in clinical practice. Single cell sequencing technology is high-throughput sequencing of the genome， transcriptome， or epigenome at the single-cell level， in order to reveal cellular heterogeneity， and to understand the developmental trajectory， type， state， and various interactions of cells. Since its first discovery， single-cell sequencing technology has been widely applied in various fields， especially in early diagnosis and personalized treatment of tumors. This article mainly reviews the application and progress of single-cell sequencing in various organ dysfunctions caused by IRI， so as to further understand the mechanisms and signaling pathways of IRI， and to provide new ideas for targeted therapy of organ IRI.

In the process of accelerating the construction of a strong country in health and sports in China， the mode of promoting health has shifted from passive health to active health. Guided by the concept of “active health”， there is a new understanding of the relationship between sports， health， and medical care. The integration of sports and medicine is a concrete manifestation and implementation of the concept of “active health”， and an important measure to implement the Healthy China strategy， which is regarded as an important strategy to promote public health reform. This article reviews the historical path of the integration of sports and medicine from its concept to practical implementation， and finds that China proposed the integration of sports and medicine relatively late， but it has become an intense focus of academic research； The sports and medical departments have launched guidelines for chronic disease exercise and standards related to exercise prescriptions， and local governments in China have explored diversified models of integrating sports and medicine； Under the institutional requirements of top-level design， the exploration of the “integration of sports and medicine” model is flourishing. There are currently problems in promoting the integration of sports and medicine， such as the lack of a “sports and medicine integration” system and a shortage of “sports and medicine integration” talents. Drawing on the international experience of integrating sports and medical services in other countries，We propose a development strategy of “concept first， government leading， and sports and medical cooperation”； We recommend institutional optimization such as improving medical insurance related systems， establishing certification， employment， and management systems for integrated sports and medical talents， and improving the training system for integrated sports and medical talents in universities； We also advocate propose a “dual wheel” promotion path of upgrading hospital rehabilitation centers and expanding community health centers， in order to provide reference for policy formulation and promote the integration of sports and medicine to play a greater role in China’s public health.

ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group （Saline） and hypertension group （Ang Ⅱ， which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps）， and supplemented daily with nicotinamide mononucleotide （300 mg/kg）， a precursor of NAD⁺. Blood pressure， endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA， SIRT3 and isocitrate dehydrogenase 2 （IDH2）. 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS， eNOS， SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure （P<0.001） and improved endothelial function and arterial stiffness （P<0.001） in hypertensive mice. In vitro， NMN improved endothelial function in AngII-stimulated endothelial cells （P<0.05） and attenuated mitochondrial oxidative stress levels （P<0.001）. Mechanistically， NMN elevated SIRT3 activity （P<0.001）， which subsequently enhanced IDH activity （P<0.001） and reduced oxidative stress levels in endothelial cells. Conversely， knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function （P<0.001）. ConclusionNAD⁺ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.