[摘 要] 目的：探讨含溴结构域蛋白1（BRD1）通过调控PI3K/AKT信号通路影响非小细胞肺癌（NSCLC）进展的作用机制。方法：利用TIMER 3.0数据库评估BRD1作为免疫治疗标志物的预测价值。利用慢病毒体系构建稳定过表达BRD1及N端截短突变体BRD1-ΔN的人肺癌细胞A549和NCI-H1299。采用CCK-8实验、克隆形成实验、划痕愈合实验及Transwell实验检测过表达BRD1/BRD1-ΔN对细胞增殖和迁移能力的影响；流式细胞术和Western blotting检测细胞凋亡水平及凋亡相关蛋白的变化。RNA-seq筛选受BRD1/BRD1-ΔN影响的信号通路，Western blotting及体外激酶实验验证BRD1/BRD1-ΔN过表达对AKT磷酸化的调控作用。采用AKT抑制剂LY294002处理过表达BRD1/BRD1-ΔN的NCI-H1299细胞，结合功能实验（CCK-8实验、划痕愈合实验）明确过表达BRD1/BRD1-ΔN促进细胞的增殖和迁移是否依赖AKT活化。通过RNA-seq联合KEGG/GSEA分析、免疫共沉淀（Co-IP）、RT-qPCR，鉴定整合素α2（ITGA2）是促进AKT活化的关键分子；通过Co-IP、敲低ITGA2、Western blotting及功能实验明确ITGA2在BRD1调控AKT活化中的具体作用。结果：数据库分析显示，BRD1可作为NSCLC免疫治疗的中等预测标志物（AUC = 0.625）。过表达BRD1/BRD1-ΔN显著增强了NSCLC细胞的增殖和迁移能力（P < 0.01或P < 0.001），但不影响细胞凋亡及凋亡相关蛋白的表达（均P > 0.05）；RNA-seq分析表明过表达BRD1/BRD1-ΔN主要富集于PI3K/AKT信号通路。Western blotting及体外激酶实验显示，BRD1/BRD1-ΔN过表达不影响AKT上游激酶（PDK1）的磷酸化，也不改变AKT的乙酰化修饰水平（均P > 0.05）；AKT抑制剂LY294002处理过表达BRD1/BRD1-ΔN细胞，发现BRD1/BRD1-ΔN促细胞增殖和迁移的作用部分依赖AKT的活化；RT-qPCR及Western blotting证实，BRD1过表达可上调ITGA2的mRNA和蛋白水平，敲低ITGA2则可逆转BRD1诱导的AKT激活及细胞增殖和迁移能力的增强。结论：BRD1是NSCLC的一种新型促癌因子，其通过上调ITGA2表达激活AKT信号通路，进而促进肺癌细胞的增殖和迁移。

ObjectiveTo investigate the protective effect of Rehmanniae Radix iridoid glycosides （RIG） on the kidney tissue of streptozotocin （STZ）-induced diabetic mice and explore the underlying mechanism. MethodsTwelve of 72 male C57BL/6J mice were randomly selected as the normal group， and the remaining 60 mice were fed with a high-fat diet for six weeks combined with injection of 60 mg·kg^-1 STZ for 4 days to model type 2 diabetes mellitus. The successfully modeled mice were randomized into model， metformin （250 mg·kg^-1）， catalpol （100 mg·kg^-1）， low-dose RIG （RIG-L， 200 mg·kg^-1） and high-dose RIG （RIG-H， 400 mg·kg^-1） groups （n=11）. Mice in each group were administrated with corresponding drugs， while those in the normal group and model group were administrated with the same dose of distilled water by gavage once a day. After 8 weeks of intervention， an oral glucose tolerance test （OGTT） was performed， and the area under the curve （AUC） was calculated. After mice were sacrificed， both kidneys were collected. The body weight， kidney weight， and fasting blood glucose （FBG） were measured. Biochemical assays were performed to measure the serum levels of triglycerides （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the serum level of fasting insulin （FINS）， and the insulin sensitivity index （ISI） and homeostatic model assessment for insulin resistance （HOMA-IR） were calculated. The pathological changes in kidneys of mice were observed by hematoxylin-eosin staining and Masson staining. The immunohistochemical method （IHC） was employed to assess the expression of interleukin-1 （IL-1）， interleukin-6 （IL-6）， tumor necrosis factor-α（TNF-α）， transforming growth factor-β₁ （TGF-β₁）， and collagen-3 （ColⅢ） in the kidney tissue. The protein levels of TGF-β₁， cell signal transduction molecule 3 （Smad3）， matrix metalloproteinase-9 （MMP-9）， and ColⅢ in kidneys of mice were determined by Western blot. ResultsCompared with the normal group， the model group showcased decreased body weight and ISI （P<0.01）， increased kidney weight， FBG， AUC， FINS， HOMA-IR， TC， TG， SCr， and BUN （P<0.01）， glomerular hypertrophy， capsular space narrowing， and collagen deposition in the kidney， up-regulated protein levels of IL-1， IL-6， TNF-α， TGF-β₁， ColⅢ， and Smad3 （P<0.01）， and down-regulated protein level of MMP-9 （P<0.01） in the kidney tissue. Compared with the model group， the treatment groups had no significant difference in the body weight and decreased kidney weight （P<0.05， P<0.01）. The FBG level declined in the RIG-H group after treatment for 4-8 weeks and in the metformin， catalpol， and RIG-L groups after treatment for 6-8 weeks （P<0.01）. The AUC in the RIG-L， RIG-H， and metformin groups decreased （P<0.05， P<0.01）. The levels of TC， SCr， and BUN in the serum of mice in each treatment group became lowered （P<0.05， P<0.01）. The level of TG declined in the RIG-L， RIG-H， and metformin groups （P<0.05， P<0.01）. The serum level of FINS declined in the catalpol， RIG-L， and metformin groups （P<0.01）. Compared with the model group， the treatment groups showed decreased HOMA-IR （P<0.01）， increased ISI （P<0.01）， alleviated pathological changes in the kidney tissue， and down-regulated expression of IL-1 and TGF-β₁. In addition， the protein levels of IL-6， TNF-α， and ColⅢ in the RIG-H and metformin groups and IL-6 and TNF-α in the RIG-L group were down-regulated （P<0.05， P<0.01）， and the protein levels of IL-6， TNF-α， and ColⅢ in the catalpol group and ColⅢ in the RIG-L group showed a decreasing trend without statistical difference. The protein levels of TGF-β₁， Smad3， and ColⅢ in the RIG-H and metformin groups were down-regulated （P<0.01）. Compared with that in the model group， the protein level of MMP-9 was up-regulated in each treatment group （P<0.01）. ConclusionRIG can improve the renal structure and function of diabetic mice by regulating the TGF-β₁/Smads signaling pathway.

China’s integrated elderly care and medical services model is mainly reflected in the close cooperation between medical institutions and pension institutions， providing comprehensive care services for the elderly， and has been promoted nationwide. However， this model still faces challenges， such as uneven resource distribution， inconsistent service standards， and a lack of talent. As the aging process of the population deepens continuously， the demand for integrated elderly care and medical services has increased， and relevant policies issued by the government and social concerns have brought development opportunities for this model. Scientific and technological advancements will also promote the development of integrated elderly care and medical services towards intelligence and personalization. It is expected that continuous investment in policies， capital， technology， and other aspects will be made to promote the standardization， specialization， and popularization of services to meet the needs of the elderly and improve their quality of life. The joint efforts of all sectors of society are also needed to continuously innovate service models and improve service levels， to effectively address the challenges brought by an aging society.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

BACKGROUND:Percutaneous kyphoplasty was a common surgical procedure for the treatment of osteoporotic vertebral compression fracture.However,there was no research to confirm whether percutaneous kyphoplasty could effectively correct the local kyphoplasty of the spine in patients over 80 years old with osteoporotic vertebral compression fracture.OBJECTIVE:To investigate the effect of percutaneous kyphoplasty on local kyphosis in super-aging patients with osteoporotic vertebral compression fracture.METHODS:Single-segment osteoporotic vertebral compression fracture patients treated with percutaneous kyphoplasty at the Department of Spinal Surgery,Peking University People's Hospital,from March 2016 to August 2022,were selected as the research cohort,and the follow-up data of patients in hospital and out-patient were collected.According to patients'age,patients were divided into the advanced age group(60-79 years old,n=126)and the super-aged group(＞80 years old,n=52).According to gender,body mass index,basic diseases(hypertension,diabetes,and cardiovascular diseases),fracture segments and the presence or absence of preoperative intravertebral cleft,the two groups of patients were matched 1:2 by propensity score matching.The lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative and postoperative Cobb angle,recovery rate of Cobb angle,distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture were compared between the two groups.RESULTS AND CONCLUSION:(1)After matching the propensity score,115 patients were included,with 71 patients in the advanced age group and 44 patients in the super-aged group.There was no statistically significant difference in baseline data,including gender,body mass index,hypertension ratio,diabetes ratio,cardiovascular disease ratio,fracture section,and preoperative intravertebral cleft,between the two groups(P＞0.05).The postoperative Cobb angle of the super-aged patients was significantly smaller than that of the elderly patients(P＜0.05).There was no significant difference in lumbar CT values,injection amount of bone cement,preoperative and postoperative vertebral height,preoperative collapse rate of the vertebral body,preoperative Cobb angle,recovery rate of Cobb angle,postoperative distance between the bone cement and anterior edge of the vertebral body,sagittal position of cement filling,contact between the bone cement and endplate,distance between the bone cement and vertebral endplates,bone cement distribution score,bone cement leakage,and vertebral refracture ratio between the two groups(P＞0.05).(2)These findings indicate that percutaneous kyphoplasty can effectively correct local kyphosis of the spine in super-aging patients with osteoporotic vertebral compression fractures.

Cancer incidence in China has been rising steadily,with a particularly heavy burden from several high-prevalence malignancies.Medical examination for cancer plays a critical role in the early detection of cancer,precancerous lesions,and precursor conditions,thereby facilitating timely diagnosis and intervention.Such examination also addresses the growing demand for person-alized cancer screening services among diverse population groups.The development of evidence-based,context-specific cancer screening guidelines is essential to enhance the standardization,quality,and equity of preventive screening practices across the country,ultimately improving out-comes in early cancer detection and treatment.Guided by the Department of Medical Emergency Response of the National Health Commission,the Guidelines for Medical Examination for Cancer in Health Examination Agency(2025 Edition)were developed under the leadership of the National Cancer Center.A multidisciplinary panel of experts formulated the guidelines in accordance with the principles and methodology of the World Health Organization Handbook for Guideline Deve-lopment.The guidelines provide evidence-based recommendations on key clinical domains:target cancers and populations,overall screening workflow,screening protocols,diagnostic technolo-gies,result interpretation,follow-up procedures,and quality control.The primary objective is to standardize cancer screening practices in health examination agency and strengthen China's ca-pacity for prevention and control of high-burden cancers.

To investigate the malignant progression and molecular mechanism of KHSRP regulating esophageal squamous cell carcinoma(ESCC) through the JAK1/STAT3 signaling axis.

To explore the differences in biological gas production in the waterlogged zone of a coal seam fire-affected area, in this study the in-situ gas production experiment was conducted with the mine water from aquitard layers in coal seam fire zones in Xinjiang. The results showed that the biogas production first increased and then decreased with the increase in distance, and the highest gas production reached 216.55 mL. The changes in key metabolic pathways during the anaerobic fermentation of coal were analyzed, which showed that as the distance from the aquitard layer in the coal seam fire zone increased, the methanogenesis pathways gradually shifted from acetic acid decarboxylation and carbon dioxide reduction to acetic acid decarboxylation and methylamine methanogenesis. The significant variability in the in-situ mine water reservoir conditions contributed to the differences. In addition, the reservoir pressure and temperature increased as the distance from the fire zone became longer, and the salinity of the farthest mine water in the reverse fault was the highest due to the lack of groundwater supply. Pearson correlation analysis revealed significant correlations of microbial communities with key functional genes and the types and concentrations of ions. The ions significantly influencing microbial enzymatic metabolic activities included Al³⁺, Fe²⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, Mg²⁺, PO₄^3-, and Mo⁶⁺. The differences in metabolic pathways were attributed to the integrated effects of a co-occurring environment with multiple ions. The gas production simulation experiments and metagenomic analyses provide data support for the practical application of in-situ biogas experiments, laying a foundation for engineering applications.
Biofuels ; Coal ; Methane/biosynthesis* ; Fires ; Groundwater ; Coal Mining ; Fermentation ; China ; Anaerobiosis

Pharmacotranscriptomic profiles, which capture drug-induced changes in gene expression, offer vast potential for computational drug discovery and are widely used in modern medicine. However, current computational approaches neglected the associations within gene‒gene functional networks and unrevealed the systematic relationship between drug efficacy and the reversal effect. Here, we developed a new genome-scale functional module (GSFM) transformation framework to quantitatively evaluate drug efficacy for in silico drug discovery. GSFM employs four biologically interpretable quantifiers: GSFM_Up, GSFM_Down, GSFM_ssGSEA, and GSFM_TF to comprehensively evaluate the multi-dimension activities of each functional module (FM) at gene-level, pathway-level, and transcriptional regulatory network-level. Through a data transformation strategy, GSFM effectively converts noisy and potentially unreliable gene expression data into a more dependable FM active matrix, significantly outperforming other methods in terms of both robustness and accuracy. Besides, we found a positive correlation between RS_GSFM and drug efficacy, suggesting that RS_GSFM could serve as representative measure of drug efficacy. Furthermore, we identified WYE-354, perhexiline, and NTNCB as candidate therapeutic agents for the treatment of breast-invasive carcinoma, lung adenocarcinoma, and castration-resistant prostate cancer, respectively. The results from in vitro and in vivo experiments have validated that all identified compounds exhibit potent anti-tumor effects, providing proof-of-concept for our computational approach.

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.