OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a （chsⅣ） on renal function in diabetic nephropathy （DN） model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group （i.g. administration of normal saline， high-fat diet）， chsⅣ low-dose and high-dose groups （i.g. administration of 90， 180 mg/kg chsⅣ， high-fat diet）， with 12 rats in each group. Additionally， 10 normal rats were set as the control group （i.g. administration of normal saline， regular diet）. From the 5th to the 12th week after streptozotocin injection， they were given intragastric administration of relevant drug or normal saline， once a day. After the last medication， the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine and urine protein as well as the levels of reduced glutathione （GSH）， superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were measured. Additionally， the insulin resistance index was calculated. Hematoxylin-eosin， periodic acid-Schiff， and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group， the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved， with significant decreases in renal histological scores， mesangial expansion index， and glomerulosclerosis scores （ P ＜0.05）； the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine， urine protein and homeostasis model assessment for insulin resistance， as well as MDA content， the expression levels of Notch1， Notch intracellular domain， hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased （ P ＜0.05）. The levels of GSH and SOD in renal tissue were significantly elevated （ P ＜0.05）. Moreover， the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group （ P ＜0.05）. CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity， attenuation of renal oxidative stress， and suppression of aberrant Notch signaling pathway activation.

BACKGROUND:Exercise is an effective way to improve microvascular function in patients with type 2 diabetes.In recent years,exercise has been used as an intervention therapy for microvascular dysfunction in patients with type 2 diabetes.However,few studies have systematically explored the influence of factors,such as"exercise type,exercise intensity and amount of exercise,"on microvascular function in patients.To some extent,this limits the formulation of precise exercise prescriptions to improve microvascular dysfunction in patients with type 2 diabetes and the comparison of study results.OBJECTIVE:To investigate the effects of exercise type,intensity,frequency and amount of exercise on microvascular function in patients with type 2 diabetes mellitus,and to make suggestions on exercise prescription.METHODS:The first author used computer to search the studies on the improvement of microvascular function in type 2 diabetes patients involving exercise in CNKI,WanFang,PubMed and other databases.The search terms were"diabetes mellitus,type 2 diabetes mellitus,microcirculation,microvascular reactivity,microvessels,capillaries,vasodilation,blood perfusion volume,endothelial cells,shear stress,exercise,aerobic exercise,resistance exercise,high-intensity exercise"in Chinese and English.The articles were screened by a quick glance at the article titles and abstracts to exclude those that were not closely related to the topic,and finally 60 articles were included for review.RESULTS AND CONCLUSION:(1)Exercise is an effective way to improve microvascular function in patients with type 2 diabetes.Aerobic exercise lasting 12-24 weeks,3-5 times/week,exercise time＞30 minutes and intensity between 40％and 59％reserve oxygen intake can significantly improve microvascular function in patients with type 2 diabetes.On the basis of aerobic exercise,systemic resistance exercise 2-3 times a week(50％-85％1RM,every other day)or pressure resistance exercise can obtain better intervention effects.(2)In addition,exercise can improve microvascular function in patients with type 2 diabetes in a"dose-effect"manner,and patients can get better results from the intervention by increasing the amount of exercise,while maintaining safety.(3)The mechanism of exercise improving microvascular function in patients with type 2 diabetes is mainly related to promoting the release of nitric oxide and vascular endothelial growth factor from endothelial cells and inhibiting the release of endothelin1.

BACKGROUND:Exercise is an effective way to improve microvascular function in patients with type 2 diabetes.In recent years,exercise has been used as an intervention therapy for microvascular dysfunction in patients with type 2 diabetes.However,few studies have systematically explored the influence of factors,such as"exercise type,exercise intensity and amount of exercise,"on microvascular function in patients.To some extent,this limits the formulation of precise exercise prescriptions to improve microvascular dysfunction in patients with type 2 diabetes and the comparison of study results.OBJECTIVE:To investigate the effects of exercise type,intensity,frequency and amount of exercise on microvascular function in patients with type 2 diabetes mellitus,and to make suggestions on exercise prescription.METHODS:The first author used computer to search the studies on the improvement of microvascular function in type 2 diabetes patients involving exercise in CNKI,WanFang,PubMed and other databases.The search terms were"diabetes mellitus,type 2 diabetes mellitus,microcirculation,microvascular reactivity,microvessels,capillaries,vasodilation,blood perfusion volume,endothelial cells,shear stress,exercise,aerobic exercise,resistance exercise,high-intensity exercise"in Chinese and English.The articles were screened by a quick glance at the article titles and abstracts to exclude those that were not closely related to the topic,and finally 60 articles were included for review.RESULTS AND CONCLUSION:(1)Exercise is an effective way to improve microvascular function in patients with type 2 diabetes.Aerobic exercise lasting 12-24 weeks,3-5 times/week,exercise time＞30 minutes and intensity between 40％and 59％reserve oxygen intake can significantly improve microvascular function in patients with type 2 diabetes.On the basis of aerobic exercise,systemic resistance exercise 2-3 times a week(50％-85％1RM,every other day)or pressure resistance exercise can obtain better intervention effects.(2)In addition,exercise can improve microvascular function in patients with type 2 diabetes in a"dose-effect"manner,and patients can get better results from the intervention by increasing the amount of exercise,while maintaining safety.(3)The mechanism of exercise improving microvascular function in patients with type 2 diabetes is mainly related to promoting the release of nitric oxide and vascular endothelial growth factor from endothelial cells and inhibiting the release of endothelin1.

BackgroundMonitoring the blood concentrations of antipsychotic drugs and their metabolites can guide the adjustment of clinical treatment plans， improving therapeutic efficacy while reducing adverse effects. However， there is currently a lack of a method that can accurately and efficiently quantitatively detect multiple antipsychotic drugs and their metabolites. ObjectiveTo establish a ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method for the simultaneous identification and quantitation of 12 antipsychotic drugs and their main metabolites in human serum. MethodsUsing UPLC-MS/MS technology， protein precipitation method was employed for sample pretreatment. An Agela Technologies Durashell C₈ chromatographic column （50 mm×3.0 mm， 5 μm） was selected for chromatographic separation with gradient elution. The flow rate was 0.4 mL/min， and the total analysis time was 5 minutes. The column temperature was 40℃. The mass spectrometry detection was carried out in the multiple reaction monitoring （MRM） mode， and the isotope internal standard method was used for quantification. ResultsThe relative standard deviation （RSD） of the internal standard normalization matrix effect factor for 12 antipsychotic drugs and their main metabolites at low and high quality concentrations was all less than 15%. The extraction recovery rate was 85% to 115%. They showed good linear relationships within their respective standard curve ranges （r>0.995）. At low， medium， and high quality concentrations， the accuracy was 85.24% to 114.71%， and the RSD of intra-batch and inter-batch precision was all ≤14.15%， with good stability. ConclusionAll the analytical performance indicators of this method meet the verification requirements， providing an analytical means for the quantitative detection of antipsychotic drugs and their main metabolites in human serum. ［Funded by The Third Batch of Science and Technology Projects in Chaozhou City in 2023 （number， 202303GY02）］

Cancer immunotherapy has emerged as a promising strategy. However, low response rates and immune-related side effects have plagued immunotherapy. Metallic nanoparticles, utilizing metals as their framework, are gaining prominence in cancer immunotherapy. Metal ions have shown the ability to modulate immune status by activating the cGAS-STING pathway and inducing immunogenic cell death (ICD), thereby enabling multidimensional activation of immunotherapy. Metallic nanoparticles offer significant advantages in cancer immunotherapy, leading to their increasing use in enhancing therapeutic outcomes. In view of the ever-increasing research on metallic nanoparticles, this review presents the construction, characterization, and enhanced cancer immunotherapeutic effects of different types of metal nanosystems from the perspective of the immunoregulatory mechanisms of metal ions. We delve into the current limitations and future directions of metallic nanoparticles in this rapidly evolving field. To the best of our knowledge, this review offers the most up-to-date and systematic analysis of metallic nanoparticles in immunotherapeutic applications. It is anticipated that this review of metallic nanoparticles will inspire a more refined and intelligent design of metallic nanoparticles for future research, paving the way for advancing their clinical applications.

Objective To explore the changing trend in the disease burden of gout in China from 1990 to 2021, and analyze the incidence, prevalence, and disability-adjusted life years (DALYs) by age and gender, with comparisons to global patterns, and to predict the disease burden of gout in China in 2030. Methods Data from the Global Burden of Disease (GBD) database were used to analyze changes in gout burden. Joinpoint regression was used to estimate the average annual percentage change (AAPC) with 95% confidence intervals (CIs). Comparative analyses were conducted on data from China and the world, and an ARIMA model was used to project China's gout burden in 2030. Results From 1990 to 2021, China's age-standardized incidence rate (ASIR) rose from 122.52 to 151.61/100,000, exceeding the global rise from 93.09 to 109.07/100,000. The age-standardized prevalence rate (ASPR) in China increased from 640.67/100,000 to 810.35/100,000, compared to a global rise from 536.54/100,000 to 653.81/100,000. The age-standardized DALYs rate (ASDR) in China increased from 20.2/100,000 to 25.43/100,000, surpassing the global increase from 16.67/100,000 to 20.21/100,000. AAPCs for ASIR, ASPR, and ASDR in China were 0.70%, 0.77%, and 0.75%, respectively, all higher than global rates. Middle-aged and elderly men faced the highest burden. It was predicted that there will be a decline in China's ASIR and ASPR by 2030, while ASDR will remain stable. Conclusion The disease burden of gout in China has increased significantly, outpacing global trends. Targeted interventions for hyperuricemia, particularly in elderly men, are crucial to reduce the future disease burden.

ObjectiveThis study aims to investigate the therapeutic effects of Wenweishu granule （WWSG） on functional dyspepsia （FD） with spleen-stomach deficiency cold syndrome in rats by integrating network pharmacology， molecular docking， and animal experiments. MethodsActive components and corresponding targets of WWSG were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Disease-related targets for FD with spleen-stomach deficiency cold syndrome were screened using GeneCards and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Core therapeutic targets were identified via Cytoscape and validated by molecular docking. A rat model of FD with spleen-stomach deficiency cold syndrome was established using vinegar gavage combined with tail-clamping. The rats were randomly divided into a model group， low-， medium-， and high-dose WWSG groups （2.0， 4.0， 8.0 g·kg^-1）， a domperidone group （3.0 mg·kg^-1）， a Fuzi Lizhong pillwan （0.8 g·kg^-1）， and a normal control group （n=10 per group）. Drugs were administered once daily by gavage for 14 consecutive days. After treatment， body weight， symptom scores， and gastrointestinal motility indices were recorded. Gastric and duodenal pathologies changes were observed via hematoxylin-eosin （HE） staining. Brain-gut peptides were measured in serum and tissue using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot were performed to assess stem cell factor （SCF） and receptor tyrosine kinase （c-Kit） protein expression in gastric tissues. ResultsA total of 305 drug targets， 1 140 disease targets， and 116 overlapping targets were identified. Cytoscape analysis revealed 104 core targets. Enrichment analysis indicated that the SCF/c-Kit signaling pathway was the key mechanism. Molecular docking confirmed a strong binding affinity between active components of WWSG and SCF/c-Kit proteins （binding energy<-5.1 kcal·mol^-1）. Compared with the normal group， model rats exhibited slower weight gain （P<0.05）， reduced gastric emptying and intestinal propulsion （P<0.01）， mild gastric mucosal shedding， duodenal inflammatory cell infiltration， decreased levels of gastrin （GAS）， 5-hydroxytryptamine （5-HT）， and vasoactive intestinal peptide （VIP） （P<0.05， P<0.01）， and elevated somatostatin （SS） expression （P<0.05， P<0.01）. WWSG treatment ameliorated weight gain， symptom scores， and low-grade inflammation in gastric/duodenal tissues. High-dose WWSG significantly improved gastric emptying and intestinal propulsion， upregulated GAS， 5-HT， and VIP， and downregulated SS expression in serum and tissues （P<0.05， P<0.01）. Immunohistochemistry and Western blot demonstrated that SCF and c-Kit protein expression was decreased in the model group （P<0.05， P<0.01）， which was reversed by WWSG intervention （P<0.05）. ConclusionWWSG exerts therapeutic effects on FD with spleen-stomach deficiency cold syndrome in rats， potentially by regulating the SCF/c-Kit signaling pathway to enhance gastrointestinal motility.

Objective To understand the disease spectrum of a natural village in an area with high incidence of esophageal cancer to provide a reference for precise prevention and control. Methods From 2008 to 2024, 711 asymptomatic people over the age of 35 years in a natural village with high incidence of esophageal cancer in China were surveyed, and 171 of them were subjected to gastroscopy, biopsy, and pathological examination. All participants were followed up for a long time, and their disease history was recorded. Results A total of 16 years of follow-up were performed, and 703 people were effectively followed up. In 2008, 171 people underwent gastroscopy, and 160 people had biopsy and pathological results in endoscopic screening. By 2024, 76 people had been diagnosed with malignant tumors of 12 different types, and among these people, 45 had esophageal cancer. Conclusion Esophageal cancer remains a significant cause of morbidity and mortality from malignant tumors in this region. Biopsy and pathological examination should be strengthened during gastroscopy, and follow-ups and regular check-ups should be given high importance to reduce the incidence and mortality rates of esophageal cancer.

Objective:This study systematically summarized the construction experience of the immunology platform at the Institute of Basic Medical Sciences, Peking University Third Hospital, aiming to provide theoretical references and practical guidance for research-oriented hospitals in building high-quality research platforms.Methods:This study employed case study analysis to elaborate on the platform development initiatives, integrating literature analysis and in-depth interviews to conduct a horizontal comparison of management models among peer research platforms.Results:Through five years of development, the platform had achieved remarkable outcomes via a model integrating ″Talent cultivation-Technological innovation-Equipment procurement″ Research talents had demonstrated breakthroughs in securing national-level research grants, publishing high-impact papers, and obtaining scientific awards. The technical service system had achieved enhancement in both service scope and professional depth, fostering robust interdisciplinary synergy. The platform had effectively expanded its societal engagement capacity.Conclusions:The sustainable advancement of research-oriented hospital immunology platform necessitates establishing standardized flow cytometry databases and implementing high-dimensional data integration. Building upon multidisciplinary convergence, it is imperative to pioneer innovative operational mechanisms characterized by efficiency, open-access, and shared frameworks.