With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

ObjectiveTo investigate the effect of SU056， an azo-podophyllotoxin derivative， on carbon tetrachloride （CCl₄）-induced liver fibrosis in mice and related mechanisms of action. MethodsA total of 12 mice were randomly divided into control group， model group （CCl₄+normal saline）， and treatment group （CCl₄+SU056）， with 4 mice in each group. Mice were given intraperitoneal injection of CCl₄ to establish a model of liver fibrosis， and during the middle stage of modeling， the mice in the treatment group were given daily intraperitoneal injection of SU056. Liver histopathological injury， collagen deposition， and liver function were assessed based on HE staining， Masson staining， Sirius Red staining， the content of hydroxyproline in liver tissue， and the serum levels of alanine aminotransferase and aspartate aminotransferase， and immunofluorescence assay was used to measure the expression levels of smooth muscle actin α （α-SMA）， collagen type Ⅰ， and Y-box binding protein 1 （YB1）. The human hepatic stellate cell （HSC） line LX-2 and primary mouse HSC were used， and CCK-8 assay was used to measure cell proliferation； Transwell assay was used to observe cell migration； quantitative reverse transcription-polymerase chain reaction and Western Blot were used to measure the expression levels of collagen type Ⅰ， collagen type Ⅲ， YB1， phosphorylated mammalian target of rapamycin （mTOR）， and phosphorylated S6K， so as to validate the function of the YB1/mTOR signaling axis. The one-way or two-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the mouse model of liver fibrosis induced by CCl₄， compared with the model group， the treatment group had significant alleviation of inflammatory cell infiltration， collagen deposition， and pseudolobule formation in liver tissue and significant reductions in the serum levels of alanine aminotransferase and aspartate aminotransferase and the content of hydroxyproline in liver tissue （all P<0.01）. Immunofluorescence assay showed that SU056 significantly inhibited the abnormal high expression of α-SMA， collagen type I， and YB1 in liver tissue （all P<0.01）. In vitro experiments showed that SU056 inhibited the transforming growth factor-β1-induced proliferation of LX-2 cells （P<0.01）， the migration of LX-2 cells （P<0.05）， and the transcriptional up-regulation of collagen type Ⅰ and collagen type Ⅲ （all P<0.05） in a dose-dependent manner， and SU056 could inhibit the spontaneous activation of primary HSC in vitro. Mechanistic studies revealed that transforming growth factor-β1 simultaneously upregulated the expression levels of YB1， phosphorylated mTOR， and phosphorylated S6K in LX-2 cells， and treatment with SU056 （10 and 20 µmol/L） could downregulate the protein expression levels of collagen type I， YB1， phosphorylated mTOR， and phosphorylated S6K. Specific knockdown of YB1 or administration of the mTOR inhibitor rapamycin exerted a similar effect as SU056. SU056 also inhibited the co-upregulation of α-SMA and phosphorylated mTOR in liver tissue of model mice （P<0.01）. ConclusionSU056 can effectively inhibit HSC activation， proliferation， migration， and extracellular matrix production both in vivo and in vitro and thus delay the progression of liver fibrosis， by disrupting the YB1/mTOR positive feedback signaling axis.

Background Long-term exposure to ambient fine particulate matter (PM_2.5) is a significant risk factor for cardiometabolic disorders. However, the mechanisms of its interaction with the endogenous circadian system remain incompletely understood. Objective To investigate whether chronic PM_2.5 exposure interferes with the rhythmic expression of the cardiac circadian clock, thereby disrupting downstream antioxidant defenses and metabolic homeostasis, and ultimately driving cardiometabolic dysfunction. Methods Seventy-two male C57BL/6 mice were randomly divided into a PM_2.5 exposure group (PM group) and a filtered air control group (FA group). Whole-body exposure was conducted for 8 weeks in a meteorological environmental animal exposure system. Samples were collected at six distinct zeitgeber time (ZT) points post-exposure. The 24 h ambulatory blood pressure and serum lipid profiles were monitored. Rhythm parameters were derived via cosinor analysis to compare differences in Midline statistic of rhythm (Mesor), amplitude, and phase between the two groups. The rhythmic expression of core circadian clock genes and antioxidant genes in the myocardium was detected by quantitative polymerase chain reaction (qPCR). Myocardial reactive oxygen species (ROS) levels and downstream pathway protein expression were analyzed by immunofluorescence and Western blot (WB), respectively. The expression changes of the clock gene retinoic acid receptor-related orphan receptor α (RORα) were assessed at both the mRNA and protein levels. Finally, Spearman correlation analysis was used to explore the relationships among myocardial RORα expression, lipid profiles, and oxidative stress indicators. Results Compared to the FA group, mice in the PM group exhibited a blunted circadian rhythm in blood pressure, characterized by sustained elevation throughout the day. Chronic PM_2.5 exposure showed a significant interaction with ZT on systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) (F-interaction=9.11, 5.70, and 6.02, respectively; P<0.05), as well as on serum triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) (F-interaction=16.32, 11.12, 15.39, and 28.09, respectively; P<0.05). Cosinor analysis further revealed that the Mesor values of T-CHO, TG, and LDL-C were significantly increased (P<0.05), while that of HDL-C was significantly decreased in the PM group (P<0.05). The oscillation amplitudes of SBP, DBP, and MAP showed a decreasing trend, whereas those of TG and LDL-C were significantly increased (P<0.05). Furthermore, SBP, T-CHO, and HDL-C all exhibited a significant phase delay (P<0.05). Mechanistically, PM_2.5 exposure significantly suppressed the expression of the positive circadian regulator RORα in the myocardium, leading to disordered rhythmic expression of core clock genes (Bmal1, Clock, Per1/2, and Cry1/2). This exposure also inhibited the rhythmic expression of antioxidant genes (GPX1, SOD2, and CAT), resulting in increased ROS generation and elevated expression of calcium/calmodulin-dependent protein kinase II (CaMKII) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) proteins. Correlation analysis further revealed that myocardial RORα expression level was negatively correlated with T-CHO, TG, and LDL-C (r=−0.55, −0.63, and −0.51, respectively; P<0.001), and positively correlated with HDL-C (r=0.37, P=0.010), and antioxidant genes GPX1, SOD2, and CAT expression (r=0.34, 0.35, and 0.56, respectively; P < 0.001). Conclusion Chronic PM_2.5 exposure induces cardiometabolic dysfunction by suppressing myocardial RORα expression. This suppression disrupts the cardiac circadian clock and the diurnal balance of oxidative stress, triggering oxidative damage and elevating expression of CaMKII/NADPH pathway proteins. Collectively, these alterations precipitate the loss of cardiac metabolic rhythms and subsequent functional impairment.

With the accelerating aging of the population, the proportion of elderly patients with lung cancer continues to rise, presenting multiple challenges to perioperative management. This paper systematically reviews the clinical characteristics of elderly lung cancer patients. Based on the comprehensive geriatric assessment, it proposes incorporating seven major geriatric syndromes—frailty, delirium, sarcopenia, cognitive impairment, malnutrition, dysphagia, and mood disorders—into the core evaluation system. By integrating multimorbidity management with complication prevention and control, an integrated "geriatric syndrome-multimorbidity-complication" perioperative management model is constructed. Furthermore, this paper outlines stratified intervention strategies for geriatric syndromes, a "five-step" workflow for comorbidity management, and a comprehensive intervention pathway for complications across the preoperative, intraoperative, and postoperative phases. Multidisciplinary team (MDT) collaboration serves as the core mechanism to achieve individualized comprehensive treatment. This paper aims to provide a novel perioperative comprehensive treatment model for elderly lung cancer patients, which is centered on geriatrics, supported by multidisciplinary collaboration, and guided by precision medicine.

In 2026， the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases jointly published a Delphi consensus statement on surrogate endpoints and real-world evidence in primary biliary cholangitis. This consensus proposes 16 statements and 42 recommendations centering on the following three most critical issues in the development of new drugs for primary biliary cholangitis： whether liver biochemical parameters and noninvasive assessments of liver fibrosis can be used as surrogate endpoints for clinical outcomes； how real-world data and real-world evidence can complement or support confirmatory studies in a manner compliant with regulatory requirements； how patient-reported outcomes can be standardized for the assessment of quality of life， pruritus， and fatigue. This article provides an excerpt and expert interpretation of the background， methodological framework， core statements， recommendations， and key figures and tables of this consensus， in order to provide a reference for the diagnosis and treatment of primary biliary cholangitis， drug evaluation， real-world study design， and the development of patient-centered clinical endpoints in China.

ObjectiveTo explore the long-term dynamic trajectories of fasting blood glucose （FBG） and insulin resistance （IR） in patients with type 2 diabetes mellitus （T2DM） and their influencing factors. MethodsThis retrospective cohort study included 1 896 T2DM patients registered at Tongren Hospital from May 2020 to May 2025. Based on longitudinal follow-up data of FBG and fasting insulin， joint latent class mixed models （JLMM） were applied to identify FBG-IR trajectories. Univariate and multinomial logistic regression was used to examine demographic characteristics， lifestyle， and clinical determinants of trajectory type. ResultsFour distinct FBG-IR trajectories were identified： stable FBG-IR （9.76%）， rising FBG-stable IR （5.01%）， stable FBG-elevated IR （75.90%）， and elevated FBG-IR （9.34%）. Compared with the stable FBG-IR group， age ≥60 years was protective against the elevated FBG-stable IR trajectory （OR=0.55， 95%CI：0.33-0.92， P=0.023）. Highereducation increased the risk of stable FBG-elevated IR （OR=1.40， 95%CI：1.01-1.94， P=0.046）. Abnormal blood pressure was associated with lower risks of stable FBG-elevated IR （OR=0.66， 95%CI：0.48-0.92， P=0.013） and elevated FBG-IR （OR=0.48， 95%CI：0.31-0.74， P=0.001）. Non-drinkers were less likely to belong to the stable FBG-elevated IR trajectory （OR=0.39， 95%CI：0.16-0.95， P=0.038）. ConclusionsThe evolution trajectory of FBG and IR in T2DM patients shows significant heterogeneity. The majority of patients have a deterioration of IR first. Age， education level， blood pressure， and alcohol consumption are the main influencing factors. Joint assessment of FBG and IR is helpful for early identification of high-risk individuals and guiding individualized intervention.

Objective: To investigate the predictive value of EZH2 expression for malignant transformation in oral leukoplakia (OLK) and to provide a reference for clinical practice. Methods: This study was approved by the institutional ethics committee, and informed consent was obtained from all participants. A total of 114 patients diagnosed with OLK by pathological examination and treated at our hospital between November 2020 and July 2022 were initially enrolled. After excluding those with incomplete data or follow-up, 105 participants were included in the final analysis, comprising 14 in the high EZH2 expression group and 91 in the low EZH2 expression group. Histopathological examination of oral mucosa and immunohistochemical detection of EZH2 protein expression were performed. The follow-up period was 30 months; participants were followed until malignant transformation occurred or until the end of follow-up, at which point they were withdrawn from the study. The exposure factor was the level of EZH2 protein expression, and the outcome was the malignant transformation rate of OLK. Differences in EZH2 expression levels and transformation outcomes were analyzed. Results: There were no statistically significant differences between the high and low EZH2 expression groups in terms of age, sex, history of systemic disease, lifestyle habits, psychological status, diet, and sleep conditions (P > 0.05). Lesions in the high EZH2 expression group were mainly located on the ventral tongue, while in the low EZH2 expression group, they were more commonly found on the dorsal tongue and buccal mucosa. The malignant transformation rate was 28.6% (4/14) in the high expression group and 8.8% (8/91) in the low expression group; these differences were not statistically significant (P=0.053). In univariate Cox regression analysis, the risk of malignant transformation in the high EZH2 expression group was 3.647 times that of the low EZH2 expression group (HR = 3.647, 95% CI: 1.097-12.120, P<0.05). Kaplan-Meier survival analysis showed that over the 30-month follow-up period, the cancer-free survival rate in the high EZH2 expression group was 19.8% lower than in the low expression group, and the difference was statistically significant (P<0.05). In multivariate Cox regression analysis, only moderate and severe epithelial dysplasia were identified as independent risk factors for malignant transformation. The risk of malignant transformation in the moderate and severe dysplasia groups was 10.695 and 13.623 times higher, respectively, than in the mild dysplasia group (HR = 10.695, 95% CI: 2.270-50.396, P<0.05; HR=13.623, 95% CI: 1.918-96.774, P<0.05). EZH2 high expression was not an independent risk factor in the multivariate model (HR= 2.528, 95% CI: 0.752-8.500, P = 0.134). Conclusion High EZH2 protein expression is a risk factor for the malignant transformation of OLK but does not have independent predictive value.

ObjectiveTo investigate the current status of emergency management for severe mental disorders in Shanghai, and to provide countermeasures and suggestions for the establishment of a sound emergency management system for severe mental disorders and the enhancement of emergency management capability. MethodsA questionnaire survey and qualitative interviews were used to conduct an investigation into the emergency management in 17 district-level mental illness prevention and control institutions in Shanghai, which includes the basic situation of emergency management for severe mental disorders, the construction of emergency response teams and personnel, emergency preparedness drills and training, emergency management plans and rules and regulations, and problems encountered in emergency management. ResultsIn terms of emergency management mechanism and basic situation, resources such as personnel allocation, security funds and green channel were well equipped in each district-level mental illness prevention and control institution in Shanghai. However, the equipment of some hardware facilities was still insufficient to some extent. Therefore, further improvement on the emergency management mechanism for severe mental disorders was needed. With regard to the construction of emergency team and personnel allocation, the majority were those aged between 35‒<45 years old, with a bachelor’s degree, and more than 10 years of working experience. For example, 90.27% staff in district-level mental illness prevention and control institution had a bachelor’s degree or above, which was higher than that among the staff in community-level (73.60%); staff majored in clinical medicine in district-level institution accounted for the proportion at 52.71%, higher than that among the staff in community-level (28.86%); 57.24% staff in district-level institution had an intermediate professional title, higher than that among the staff in community-level (42.28%); and 69.90% staff in district-level institution had more than 10 years of working experience, higher than that among the staff in community-level (43.62%). In the aspect of emergency drills and training, all district-level mental illness prevention and control institutions in Shanghai had a high demand for emergency training, and the weak aspects mainly focused on lack of emergency service protocols, skills of addressing technical challenges, and construction of effectiveness evaluation system. Moreover, the teaching methods were primarily centered on case analysis, simulation drills, interactive discussions, and so forth. Concerning emergency management plans and rules and regulations, all districts in Shanghai had relatively established well-developed systems for emergency response plans, emergency response leadership groups, and emergency response operational task forces for severe mental disorders. About half of the institutions had established other rules and regulations related to emergency management of severe mental disorders in addition to emergency plans. ConclusionShanghai has initially established an emergency management system for severe mental disorders, but it is still fragile in specialized training for emergency management of severe mental disorders, construction of emergency management mechanisms, and the building-up of grassroots emergency teams. Further priorities should include strengthening emergency management training, enhancing the construction of emergency management personnel teams, and gradually establishing a more comprehensive and integrated emergency management mechanism for severe mental disorders.

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.