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.

Objective To explore the clinical characteristics and related prognostic factors of hypertriglyceridemia acute pancreatitis (HTG-AP). Methods A retrospective analysis was conducted on 350 patients with HTG-AP admitted to HanZhong Central Hospital from March 2019 to March 2024. All patients received conventional treatment. They were followed up for one year after treatment. The prognosis of the patients was statistically analyzed, and logistic regression was used to analyze the related factors of prognosis. Results HTG-AP patients had an acute onset, with clinical symptoms of sudden upper abdominal pain (329/350), nausea and vomiting (275/350), acidosis (101/350), and multiple organ failure (38/350). All patients had elevated serum TG. During the follow-up period, 123 cases had a poor prognosis (poor prognosis group), and 227 cases had a good prognosis (good prognosis group). Compared with the good prognosis group, the patients in the poor prognosis group had higher levels of TG, creatinine and C-reactive protein at admission, lower levels of serum calcium and albumin, and higher proportions of diabetes mellitus history and severe conditions (P<0.05). Logistic regression analysis found that the factors related to the prognosis of patients with HTG-AP were TG level, C-reactive protein level, albumin level, history of diabetes mellitus, and moderate to severe condition (P<0.05). Conclusion HTG-AP patients have an acute onset and have main clinical symptoms of sudden upper abdominal pain, nausea and vomiting. Some patients experience systemic inflammatory reactions such as acidosis and multiple organ failure, and they may also have significantly increased serum TG. TG, C-reactive protein, albumin, history of diabetes mellitus, and severe disease conditions are associated with the prognosis of HTG-AP patients.

Objective To investigate the role and potential mechanism of secreted phosphoprotein 1 (SPP1)⁺ macrophages in the formation of chronic renal allograft fibrosis. Methods The expression features of SPP1⁺ macrophages in renal allografts of chronic allograft dysfunction (CAD) patients were analyzed based on single-cell transcriptome data of renal tissues from patients with CAD. Transcription factor VIPER analysis and DoRothEA transcription factor activity analysis were performed on the single-cell transcriptome data. Renal tissue samples were collected from kidney transplant recipients, including the CAD group (n=5) and the non-renal allograft fibrosis group (CTL group, n=5). A mouse model of chronic allograft rejection was established and divided into the allogeneic kidney transplantation group (CAD group, n=3) and the syngeneic kidney transplantation group (SYN group, n=3). Hematoxylin-eosin staining was used to detect renal tissue injury in mice, and Masson staining was used to detect renal tissue fibrosis. Immunofluorescence staining was performed to detect SPP1 expression in renal tissues of transplant recipients and mouse renal allografts. Bone marrow-derived macrophages (BMDMs) were extracted from mice and subjected to hypoxia stimulation. The expression of hypoxia-inducible factor (HIF)-1α and SPP1 was detected by Western blot, and SPP1 expression was detected by flow cytometry. BMDMs were transfected with HIF-1α overexpression plasmid and HIF-1α small interfering RNA (siRNA) followed by hypoxia intervention, and the expression of HIF-1α and SPP1 was detected by Western blot. Mouse aortic endothelial cells (MAECs) were co-cultured with the supernatant of BMDMs, and the expression of endothelial-mesenchymal transition (EndMT)-related markers was detected by Western blot and immunofluorescence. Results Single-cell transcriptome analysis showed that the proportion of SPP1⁺ macrophages in renal allograft tissues was significantly higher in the CAD group than in the CTL group (P<0.05). The renal injury score and the percentage of interstitial fibrotic area in the CAD group were significantly higher than those in the SYN group (both P<0.05). Immunofluorescence staining showed that the proportion of SPP1⁺ macrophages was increased in the CAD group compared with the CTL group, and also increased in the CAD group compared with the SYN group (both P<0.05). VIPER analysis and DoRothEA transcription factor activity analysis revealed activation of the hypoxia pathway and upregulated expression of transcription factors such as HIF-1α in SPP1⁺ macrophages. SPP1 expression was elevated in BMDMs under hypoxic conditions. Knockdown of HIF-1α inhibited hypoxia-induced SPP1 protein expression, whereas overexpression of HIF-1α upregulated SPP1 protein levels. After co-culture of hypoxia-induced BMDMs with MAECs, the expression levels of EndMT-related markers were increased. Conclusions SPP1⁺ macrophages differentiated under hypoxia are significantly infiltrated in the formation of chronic renal allograft fibrosis, and may promote renal allograft fibrosis by inducing EndMT in renal vascular endothelial cells.

BACKGROUND:Sarcopenia is an age-related systemic skeletal muscle disease,which is associated with a variety of adverse outcomes such as falls,functional decline,frailty,and death.Postmenopausal women are one of the high-risk groups for sarcopenia.OBJECTIVE:To develop a predictive model for assessing the risk of sarcopenia in Chinese postmenopausal women based on high-quality database.METHODS:Data for this study were derived from 2 370 postmenopausal women from the China Health and Retirement Longitudinal Study(CHARLS),and sarcopenia was assessed using the Asian Working Group on Sarcopenia 2019(AWGS2019)recommended metrics.The study cohort was randomized into a training set(70％)and a validation set(30％).Risk factors for sarcopenia in postmenopausal women were screened using the least absolute shrinkage and selection operator,ten-fold cross-validation,and logistic regression.Nomogram predicting the risk of sarcopenia in postmenopausal women was constructed based on the risk factors,and the model efficacy was evaluated by the receiver operating characteristic curve and area under the curve(AUC),calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:The prevalence of sarcopenia in this study was 23.50％and age,place of residence,sleep quality,cognitive function,depression,and the number of chronic diseases were selected as predictors of sarcopenia in postmenopausal women.The nomogram model showed good discrimination between the training and validation sets,with an AUC value of 0.751(95％confidence interval=0.724-0.778,P＜0.001),a specificity of 72.2％,and a sensitivity of 63.2％in the training set,and an AUC value of 0.763(95％confidence interval=0.721-0.805,P＜0.001),with a specificity of 69.6％and a sensitivity of 70.8％.The calibration curve showed a relatively significant agreement between the nomogram model and the actual observations,and the decision curve analysis demonstrated broad and good clinical utility.To conclude,the nomogram to assess the risk of sarcopenia constructed based on age,place of residence,sleep quality,cognitive function,depression,and number of chronic diseases,provides an effective tool for identifying and eliminating risk factors for sarcopenia in Chinese postmenopausal women,and helps to reduce the incidence of sarcopenia.

BACKGROUND:Sarcopenia is an age-related systemic skeletal muscle disease,which is associated with a variety of adverse outcomes such as falls,functional decline,frailty,and death.Postmenopausal women are one of the high-risk groups for sarcopenia.OBJECTIVE:To develop a predictive model for assessing the risk of sarcopenia in Chinese postmenopausal women based on high-quality database.METHODS:Data for this study were derived from 2 370 postmenopausal women from the China Health and Retirement Longitudinal Study(CHARLS),and sarcopenia was assessed using the Asian Working Group on Sarcopenia 2019(AWGS2019)recommended metrics.The study cohort was randomized into a training set(70％)and a validation set(30％).Risk factors for sarcopenia in postmenopausal women were screened using the least absolute shrinkage and selection operator,ten-fold cross-validation,and logistic regression.Nomogram predicting the risk of sarcopenia in postmenopausal women was constructed based on the risk factors,and the model efficacy was evaluated by the receiver operating characteristic curve and area under the curve(AUC),calibration curve,and decision curve analysis.RESULTS AND CONCLUSION:The prevalence of sarcopenia in this study was 23.50％and age,place of residence,sleep quality,cognitive function,depression,and the number of chronic diseases were selected as predictors of sarcopenia in postmenopausal women.The nomogram model showed good discrimination between the training and validation sets,with an AUC value of 0.751(95％confidence interval=0.724-0.778,P＜0.001),a specificity of 72.2％,and a sensitivity of 63.2％in the training set,and an AUC value of 0.763(95％confidence interval=0.721-0.805,P＜0.001),with a specificity of 69.6％and a sensitivity of 70.8％.The calibration curve showed a relatively significant agreement between the nomogram model and the actual observations,and the decision curve analysis demonstrated broad and good clinical utility.To conclude,the nomogram to assess the risk of sarcopenia constructed based on age,place of residence,sleep quality,cognitive function,depression,and number of chronic diseases,provides an effective tool for identifying and eliminating risk factors for sarcopenia in Chinese postmenopausal women,and helps to reduce the incidence of sarcopenia.

Background: The tight junction protein claudin18.2 (CLDN18.2) has been implicated in poor prognosis and suboptimal immunotherapy response in gastric cancer (GC). This study investigates the clinicopathological relevance of CLDN18.2 expression and its association with molecular subtypes in GC patients from a high-incidence region, combining transcriptomic and proteomic approaches to explore how CLDN18.2 contributes to progression and metastasis. Methods: A retrospective cohort of 494 GC patients (2019–2024) underwent immunohistochemical analysis for CLDN18.2, Epstein-Barr virus (Epstein–Barr virus–encoded RNA), p53, human epidermal growth factor receptor 2 (HER2), and mismatch repair proteins (MLH1, MSH2, PMS2, and MSH6). CLDN18.2 positivity was defined as moderate to strong (2+/3+) membranous staining in ≥75% of tumor cells. Clinicopathological correlations, biomarker associations, and survival outcomes were evaluated. Transcriptomic and proteomic sequencing was performed to explore molecular mechanisms. Results: CLDN18.2 positivity was observed in 26.9% (133/494) of gastric adenocarcinomas. CLDN18.2-positive tumors correlated with TNM stage (p = .003) and shorter overall survival (p = .018). No associations were identified with age, sex, HER2 status, microsatellite instability, or Epstein-Barr virus infection. Transcriptomic profiling revealed CLDN18.2-high tumors enriched in pathways involving cell junction disruption, signaling regulation, and immune modulation. Proteomic profiling showed that tumors with high CLDN18.2 were enriched in multiple mechanism-related pathways such as integrated metabolic reprogramming, cytoskeletal recombination, immune microenvironment dysregulation, and pro-survival signaling. These mechanisms may collectively contribute to tumor progression and metastasis. Conclusions CLDN18.2 overexpression is associated with poor prognosis in GC patients. Transcriptomic and proteomic analyses demonstrate that CLDN18.2 promotes tumor progression and metastasis, underscoring its potential as an independent prognostic factor in regions with a high incidence of GC.

Animal experiments are essential tools in biomedical research, serving as a bridge between basic research and clinical trials. Systematic reviews and meta-analyses (SRs/MAs) of animal experiments are crucial methods for integrating evidence from animal experiment, which can facilitate the translation of findings into clinical research, reduce translational risks, and promote resource integration in basic research. With the continuous development of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, its application in SRs/MAs of animal experiments has gained increasing attention. This article first outlines the principles and specific applications of the GRADE methodology in SRs/MAs of animal experiments, including qualitative descriptive systematic reviews, meta-analyses, and network meta-analyses. It then deeply analyzes the misuse of the GRADE methodology in practice, including incorrect evidence grading, improper classification of evidence, misapplication in qualitative systematic reviews, inconsistencies between the documentation of the upgrading and downgrading process and results, and inappropriate use for making recommendations. Furthermore, this article comprehensively discusses the factors influencing the grading of evidence certainty in SRs/MAs of animal experiments, including the impact of bias risk, indirectness, inconsistency, imprecision, and publication bias on evidence downgrading, as well as the role of large effect sizes and cross-species consistency in evidence upgrading. Finally, in response to the issues discussed, improvement strategies are proposed, including further research and optimization of the GRADE methodology for SRs/MAs of animal experiments, the development of reporting guidelines tailored to the characteristics of SRs/MAs in animal experiment research, and enhanced professional training for researchers in the GRADE methodology. This article aims to improve the quality of evidence in SRs/MAs of animal experiments, strengthen their reliability in clinical decision-making, and promote the more efficient translation of findings from animal experiment research into clinical practice.

Objective : To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis. Methods : An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression. Results : Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01). Conclusion Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.

With the development of brain-computer interface technology （BCI）， its potential to enhance human cognitive and physical abilities continues to emerge， while also stimulating the“superhuman”enhancement impulse to try to push the boundaries of treatment. Overmodification of the body governed by the pursuit of BCI“superhuman”augmentation may lead to a series of ethical body dilemmas， such as issues of bodily autonomy， the risk and benefit of the body medical dimension， and how to define the idealized body at the social level when the natural body and the BCI technology-enhanced body compete in the future. Therefore， it is necessary to take positive measures to promote the development of brain-computer interface technology in the process of continuous innovation and ethical responsibility.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.