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.

As the core vehicle for preserving and transmitting traditional Chinese medicine（TCM） academic thought and clinical experience， the establishment of a robust quality evaluation system for TCM clinical case reports is a crucial component in the current standardization and modernization of TCM. Based on the practical experience of constructing the China Clinical Cases Library of Traditional Chinese Medicine by the China Association of Chinese Medicine， this study conducted a comprehensive analysis of critical challenges， including insufficient authenticity and unfocused evaluation criteria. It proposed a three-dimensional evaluation framework grounded in the structure-process-outcome logic， encompassing three dimensions of authenticity and standardization， characteristics and advantages， application and translational impact. This framework integrated 12 key evaluation indicators in a systematic manner. The model preserved the academic characteristics of TCM syndrome differentiation and treatment， while aligning with modern scientific research standards， achieving a balance between individualized TCM experience and standardized evaluation. Concurrently， this study provided theoretical foundations and methodological guidance for evaluating the quality of TCM clinical cases， contributing significantly to the inheritance of TCM knowledge， evidence-based practice， and the reform of talent evaluation mechanisms.

The disease-syndrome combination model of spleen deficiency with dampness pattern in ulcerative colitis（SDDP-UC） is an important experimental carrier for traditional Chinese medicine （TCM） research on the prevention and treatment of ulcerative colitis （UC）， and the quality of model construction and evaluation directly influences the scientific rigor and translational value of related research conclusions. However， this field still lacks methodological synthesis and a standardized consensus. Based on a comprehensive review of existing literature， this paper summarized isomorphic cues between the spleen deficiency with dampness pattern and UC across four dimensions， including energy metabolism， immune homeostasis， mucosal barrier， and intestinal microecology. The cues were mainly involved in impaired mitochondrial energy supply and glucose metabolic reprogramming， a lowered pro-inflammatory threshold of innate immunity with insufficient adaptive immune regulation， disruption of epithelial barrier gating accompanied by compromised repair capacity， and attenuation of the luminal hypoxia barrier with accumulation of toxic metabolites. A mutually reinforcing process between local "form damage" and systemic "Qi depletion" was further interpreted from a holistic perspective. Regarding modeling strategies， existing studies predominantly use rats as the carrier， apply combined interventions such as improper diet， external damp exposure， and fatigue-related dysregulation to establish the spleen deficiency with dampness pattern background， and subsequently superimpose chemical stimulation to induce UC-like colonic damage， with a total modeling period generally spanning three to four weeks. In terms of the evaluation system， a multidimensional framework integrating syndrome assessment， histopathology， mechanistic indices， and pharmacodynamic counter-verification was outlined. On this basis， current methodological bottlenecks of models were systematically identified， including syndrome drift risk and compounded stress dilemma in temporal sequencing， syndrome confounding from etiological simulation， cross-sectional evaluation bias related to modeling duration， inadequate disease-syndrome linkage and control design within the evaluation system， and limited controls with overly single-track decision logic in formula-based syndrome verification. To address the above issues， a construction and evaluation strategy emphasizing streamlining of core etiological factors， multi-node dynamic monitoring， integration of core disease-syndrome indicator clusters， and establishment of a formula-based syndrome verification system was proposed， providing a reference for the standardized construction and scientific evaluation of the SDDP-UC model.

This study explores the therapeutic differences and mechanisms of salt-processed Phellodendri Chinensis Cortex in improving insulin resistance(IR) based on network pharmacology, molecular docking, and cellular experiments. The components and intersection targets of Phellodendri Chinensis Cortex in improving IR were collected from databases, and a "drug-component-target-disease" network and protein-protein interaction(PPI) network were constructed to screen core components and targets. A total of 29 active components and 240 intersection targets were identified, of which 13 were core targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were used to identify key signaling pathways, and molecular docking was performed to validate the binding activity between core components and targets. An IR model in HepG2 cells was induced using insulin combined with high glucose, and the effects of Phellodendri Chinensis Cortex before and after salt-processing on cell glucose consumption were evaluated. The expression of proteins related to the mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) signaling pathways was detected by Western blot. The cellular experimental results showed that, compared with the model group, glucose consumption in the drug-treated groups was significantly increased(P<0.01), the phosphorylation level of extracellular regulated protein kinase(ERK) was decreased(P<0.05), the phosphorylation levels of PI3K and AKT were increased, and the expression of glucose transporter 4(GLUT4) was also upregulated(P<0.05). Furthermore, the effect of salt-processed Phellodendri Chinensis Cortex was better than that of raw Phellodendri Chinensis Cortex. The study demonstrates that Phellodendri Chinensis Cortex, both before and after salt-processing, improves IR by regulating the expression of related proteins in the MAPK and PI3K-AKT signaling pathways, with enhanced effects after salt-processing.
Humans ; Network Pharmacology ; Phellodendron/chemistry* ; Insulin Resistance ; Drugs, Chinese Herbal/chemistry* ; Hep G2 Cells ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Glucose/metabolism*

Objective:To investigate the clinical characteristics of patients with multiple myeloma(MM)complicated by bone lesions and the risk factors associated with bone lesions.Methods:The clinical data of 294 newly diagnosed MM patients in Gansu Provincial Hospital from January 2017 to June 2021 were retrospectively analyzed.The patients were divided into the bone lesion group(154 cases)and the non-bone lesions group(140 cases)based on the presence of absence of bone lesions at diagnosis.The general data and laboratory parameters were compared between the two groups.The risk factors for bone lesions in MM patients were analyzed by logistic regression analysis,and the characteristic(ROC)curves were plotted to assess the predictive value of each risk factor for the occurrence of bone lesions in MM patients.Results:Compared to the non-bone lesion group,the bone lesion group had significantly higher serum calcium levels and significantly greater proportions of patients with Durie-Salmon(DS)stage Ⅲ,and bone pain(all P＜0.05).Logistic regression analysis showed that elevated serum calcium(OR=5.135,95％CI:1.931-13.653,P=0.001),DS stage Ⅲ(OR=1.841,95％CI:1.019-3.328,P=0.043),and bone pain(OR=8.208,95％CI:4.761-14.151,P＜0.001)were independent risk factors for bone lesions in MM patients.ROC curve analysis showed that serum calcium(AUC=0.619,95％CI:0.555-0.683,P＜0.001)and bone pain(AUC=0.743,95％CI:0.692-0.793,P＜0.001)had predictive value for bone lesions in MM patients.Conclusion:MM patients have a high incidence of bone lesions,and active monitoring and management of risk factors may improve treatment outcomes and prognosis.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective To investigate the effect of exogenous luteinizing hormone (LH) on vitrification granulosa cells and its mecha-nisms. Methods The granulosa cells of 4-week-old preadolescent mice were selected and divided into the fresh group (without vitrification procedure),the vitrification group (treated according to vitrification procedure) and the LH group (treated with 0.3 IU/L of LH intervention on the basis of the vitrification group). Granulocyte count was performed,and Realtime PCR and Western blot were used to detect the expression changes of Foxl2,PI3K,AKT and mTOR mRNAs and proteins in each group. Results Compared with the vitrification group,the total number of granulosa cells in the LH group was significantly increased (P<0.05),and the expression of Foxl2,PI3K,AKT and mTOR mRNAs and proteins were elevated (P<0.05). Conclusion The intevention of exogenous LH is beneficial for the survival of vitrifi-cation granulosa cells,and the mechanism may be related to the activation of PI3K/AKT/mTOR pathway.

Objective This study examined the association between smoking and cognitive decline through a cohort in rural population in Xi'an.Methods Data were collected from the cognitive impairment cohort of middle-aged and elderly people in rural areas of Xi'an.The cohort selected the population aged 40 years and above in rural Xi'an.The baseline survey was completed between October 2014 and March 2015,and two follow-up visits were conducted in 2016 and 2018.This study took the baseline cognitively normal population of this cohort as the research subjects.According to the survey results in 2018,the population was divided into three groups according to smoking status:smoking,quitting and non-smoking.Cognitive function was assessed by Mini-Mental State Examination(MMSE).△MMSE(2014 rating-2018 rating)≥2 was defined as cognitive decline,and △MMSE＜2 was defined as cognitive stability.Binary Logistic regression model and stratified analysis were used to analyze the relationship between smoking and cognitive decline and the influence of age on the relationship.Results A total of 1 289 subjects were included in this study.According to smoking status in 2018,they were divided into non-smokers(910,70.6％),smokers(335,26.0％),and ex-smokers(44,3.4％).In the total population,there was no significant difference in the incidence of cognitive decline among non-smokers,smokers and ex-smokers(17.3％vs.16.1％vs.15.9％,P=0.880).When stratified by age,there was no significant difference in the incidence of cognitive decline among the three groups in the subgroup of age＜65 years(16.5％vs.13.2％vs.12.1％,P=0.365).In the subgroup of age≥65 years,no significant difference was found in the incidence of cognitive decline among non-smokers,smokers and ex-smokers(20.8％vs.30.9％vs.27.3％,P=0.306).After adjusting for confounding factors,smokers had a significantly higher risk of cognitive decline than non-smokers(OR=14.139;95％CI:1.541-129.705;P=0.019).There was a trend of cognitive decline in the ex-smokers group,but with no statistical significance(OR=8.252;95％CI:0.630-108.175;P=0.108).Conclusion Smoking is positively associated with cognitive decline in the elderly,suggesting that smoking may accelerate cognitive decline in this population.