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 investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

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: 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.

Objective To investigate the registration rate and trend of pulmonary tuberculosis complicated with diabetes mellitus (PTB-DM) in Wuhan from 2020 to 2024, and to provide scientific evidence for formulating PTB-DM prevention and control policies. Methods PTB-DM case data in Wuhan (2020-2024) were collected through the Infectious Disease Registration and Management Information System. Joinpoint regression model was employed to analyze the trend of registration rates of PTB-DM among the general population and across different regions, genders, and age groups. ARIMA model was used to predict the short-term prevalence of PTB-DM. Results Among 26275 pulmonary tuberculosis cases registered in Wuhan (2020-2024), 2669 cases (10.16%) were PTB-DM. The average annual registration rate of PTB-DM was 3.96/100,000, increasing from 2.74/100,000 in 2020 to 5.40/100,000 in 2024 (APC=19.07%, 95% CI:12.99%-26.92%, P<0.001). The PTB-DM registration rates showed an upward trend across different regions, genders, and age groups in Wuhan, with higher registration rates observed in near urban area, males, and individuals aged 60~64 and 65 years and above (χ²=99.566, P<0.001; χ²=781.891, P<0.001; χ²=2211.930, P<0.001). ARIMA model predicted that the prevalence of PTB-DM in Wuhan would remain stable and fluctuating in the short time. Conclusion PTB-DM registration rate in Wuhan increases from 2020 to 2024. Near urban area, males, and elderly populations are high risk groups. Future efforts should focus on strengthening the prevention and control of PTB-DM among these populations.

ObjectiveTo examine the influencing mechanisms and regional differences in accessible facility utilization behavior among residents in eastern and central-western China. MethodsData were collected through the online questionnaire administered to residents across China using snowball sampling. Descriptive analysis and chi-square tests were conducted to compare the basic characteristics of respondents between the two regions. Welch's t test was used to compare accessible facility utilization behavior and its influencing factors. Multigroup structural equation modeling (SEM) was applied to compare the influencing mechanisms of accessible facility utilization behavior between eastern and central-western China. ResultsA total of 1 039 valid responses were obtained, including 604 from the eastern region and 435 from the central-western region. Residents in eastern regions scored significantly higher than those in central-western regions on both facility-seeking (t = 4.057, P < 0.001) and actual-using (t = 4.551, P < 0.001) behavior. The structural equation models for both regions showed identical and satisfactory goodness-of-fit indices (GFI = 0.950, AGFI = 0.932, IFI = 0.947, CFI = 0.947, RMSEA = 0.028), and all measurement and structural invariance tests met the recommended criteria. Facility configuration showed no significant direct effect on utilization behavior in eastern China, whereas a negative direct effect was observed in central-western China (β = -0.171, P = 0.047), with its influence mainly exerted indirectly through social cognition and user experience. Social cognition and user experience had significant positive effects on utilization behavior (P < 0.001). Meanwhile, social cognition indirectly influences utilization behavior through the mediating path of usage experience. The direct effects of social cognition (β = 0.406) and user experience (β = 0.510) in central-western China were greater than those in eastern China (β = 0.369 and β = 0.335, respectively). The chain mediation effect of "configuration-cognition-experience-behavior" was statistically significant in both regions (P < 0.05), with larger indirect effects observed in central-western China. ConclusionFacility configuration has a limited direct effect on accessible facility utilization, whereas social cognition and user experience play a central role, particularly in central-western China. It is recommended that the construction and renovation of accessible facility be guided by population needs, accompanied by strengthened promotion of accessibility concepts and policies, and that a transition from hardware-oriented construction to service- and management-oriented governance of accessible environments should be promoted in central-western China.

Objective To evaluate the surgical efficacy of unilateral pneumonectomy for the treatment of tuberculous destroyed lung, analyze the causes of severe postoperative complications, and explore clinical management strategies. Methods A retrospective analysis was conducted on the clinical data of patients with tuberculous destroyed lung who underwent unilateral pneumonectomy at the Public Health Clinical Center of Chengdu from 2017 to 2023. Postoperative severe complications were statistically analyzed. Patients were divided into a non-severe complication group and a severe-complication group, and the causes, management, and outcomes of complications were analyzed. Results A total of 134 patients were included, comprising 69 males and 65 females, with a mean age of 17-73 (40.43±12.69) years. There were 93 patients undergoing left pneumonectomy and 41 patients undergoing right pneumonectomy. Preoperative sputum smear was positive in 35 patients, all of which converted to negative postoperatively. There were 58 patients with hemoptysis preoperatively, and none experienced hemoptysis postoperatively. Postoperative incisional infection occurred in 8 (5.97%) patients, and postoperative pulmonary infection in 26 (19.40%) patients. Severe postoperative complications occurred in 17 (12.69%) patients, including empyema in 9 (6.72%) patients, bronchopleural fistula with empyema in 1 (0.75%) patient, severe pneumonia in 3 (2.24%) patients, postpneumonectomy syndrome in 1 (0.75%) patient, chylothorax in 1 (0.75%) patient, ketoacidosis in 1 (0.75%) patient, and heart failure with severe pneumonia in 1 (0.75%) patient. Perioperative mortality occurred in 2 (1.49%) patients, both of whom underwent right pneumonectomy. Multivariate logistic regression analysis revealed that a history of ipsilateral thoracic surgery, concomitant Aspergillus infection, and greater blood loss were independent risk factors for severe complications following unilateral pneumonectomy for tuberculous destroyed lung (P<0.05). Conclusion Unilateral pneumonectomy for patients with tuberculous destroyed lung can significantly improve the clinical cure rate, sputum conversion rate, and hemoptysis cessation rate. However, there is a certain risk of severe perioperative complications and mortality, requiring thorough perioperative management and appropriate management of postoperative complications.

Objective To systematically evaluate the efficacy and safety of proximal gastrectomy (PG) versus total gastrectomy (TG) for the treatment of Siewert type Ⅱ/Ⅲ adenocarcinoma of the esophagogastric junction (AEG). Methods PubMed, The Cochrane Library, Web of Science, EMbase, CNKI, Wanfang, and VIP databases were searched for literature comparing the efficacy and safety of PG and TG for the treatment of Siewert type Ⅱ/Ⅲ AEG. The search period was from database inception to March 2023. Meta-analysis was performed using Review Manager 5.4 software. Results A total of 23 articles were included, including 16 retrospective cohort studies, 5 prospective cohort studies, and 2 randomized controlled trials. The total sample size was 2 826 patients, with 1 389 patients undergoing PG and 1 437 patients undergoing TG. Meta-analysis results showed that compared with TG, PG had less intraoperative blood loss [MD=−19.85, 95%CI (−37.20, −2.51), P=0.02] and shorter postoperative hospital stay [MD=−1.23, 95%CI (−2.38, −0.08), P=0.04]. TG had a greater number of lymph nodes dissected [MD=−6.20, 95%CI (−7.68, −4.71), P<0.001] and a lower incidence of reflux esophagitis [MD=3.02, 95%CI (1.24, 7.34), P=0.01]. There were no statistically significant differences between the two surgical approaches in terms of operative time, postoperative survival rate (1-year, 3-year, 5-year), and postoperative overall complications (P>0.05). Conclusion PG has advantages in terms of intraoperative blood loss and postoperative hospital stay, while TG has advantages in terms of the number of lymph nodes dissected and the incidence of reflux esophagitis. There is no significant difference in long-term survival between the two surgical approaches.

This article systematically reviews and verifies the historical evolution of Stemonae Radix from the aspects of name， origin， harvesting and processing， quality and others by consulting ancient and modern literature， in order to provide reference for the development and utilization of famous classical formulas containing this medicinal herb. Stemonae Radix has a long history of application， and it derives its name from its distinctive growth pattern， featuring clusters of ten to several dozen underground tuberous roots. This morphology resembles that of certain plants in the genus Asparagus， leading to historical instances where tuberous roots from genus Asparagus were mistakenly used as Stemonae Radix. After the research， it can be concluded that Stemonae Radix was first recorded in Mingyi Bielu， and throughout history， Baidu has been recognized as its official name， though it also bears alternative names such as Baibing， Pofucao and Ye Tianmendong. The mainstream sources used throughout history have been the dried tuberous roots of Stemona sessilifolia， S. japonica or S. tuberosa from the family Stemonaceae. This aligns with the 2025 edition of Pharmacopoeia of the People's Republic of China（hereinafter referred to as Chinese Pharmacopoeia）. Additionally， Asparagus filicinus and A. officinalis from the genus Asparagus are common sources of confusion with Stemonae Radix. The three primitive plants are mainly distributed in the Yangtze River basin and southern China， exhibiting a wide distribution. Historically， wild harvesting was predominant， but cultivation is now established. In ancient times， the harvesting time was mostly in the second， third， and eighth lunar months， when roots were harvested and dried. Nowadays， it is more common to pick and excavate in the spring and autumn seasons. After excavation， the roots are washed， fibrous roots removed， briefly blanched in boiling water or steamed until no white core remains， and then sun-dried or oven-dried. In ancient times， the processing of Stemonae Radix primarily involved roasting（stir-frying）， wine roasting， or raw materials. Modern mainstream processing specifications include two types of raw and honey-roasted products. In terms of quality evaluation of the medicinal materials， ancient criteria of "preferring plump and moist roots" align with modern requirement favoring "thick， robust stems with firm texture". Evaluating quality with authenticity， since the Song dynasty， it has been highly praised to produce in Chuzhou and Hengyang as the best. It was an ancient method of fixing the production area to stabilize the medicinal origin， reflecting the ancient recognition of the therapeutic efficacy of plants belonging to the genus Stemona. The main functions of Stemonae Radix remain consistent throughout history， including relieving coughs， eliminating phlegm and parasites. Based on the research results， it is recommended that when developing famous classical formulas containing the medicinal material Stemonae Radix， the botanical source specified in the 2025 edition of Chinese Pharmacopoeia should be selected. The specific species can be determined according to the distribution of resources and the main production areas， and the origin and corresponding botanical source should be fixed. Processing methods should be chosen based on the prescription requirements. It is recommended to use raw products without specified requirements.