Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity， and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity， this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine （TCM） herbs that strengthen the spleen， regulate qi， and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation， promoting water-damp metabolism， and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness， internal accumulation of phlegm dampness" and immune dysregulation in obesity， this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

ObjectiveTo investigate the incidence of stroke in patients with type 2 diabetes mellitus (T2DM) in the community of Shanghai, and to explore its influencing factors. MethodsA two-way cohort study was used to observe the incidence of stroke in a dynamic cohort of14 743 community-based T2DM patients who were enrolled for management from January 2016 to December 2018 in Hongkou District, Shanghai. All the research subjects were followed up for 3 years to observe the stroke occurrence. Outcome events were retrospectively collected from the Shanghai Stroke and Acute Myocardial Infarction Registry Reporting Information System and the Cause of Death Registry System, and information on stroke onset and verification of past medical history were collected by family physicians through clinic follow-up, home follow-up, and telephone follow-up. Cox proportional hazards model was used to identify the risk factors of stroke in TDM2 patients, and the hazard ratio (HR) and its 95% confidence interval (CI) were calculated. ResultsAfter a mean follow up of 3.5 years, the standardized incidence of stroke in patients with T2DM was 8.65‰, and the risk of standardized incidence was 3.50 (95%CI: 3.26‒3.77) compared with that of the total national population. Cox proportional hazards regression analysis showed that age (HR=1.18, 95%CI: 1.13‒1.23), being female (HR=1.14, 95%CI: 1.01‒1.29), physical activity <600 metabolic equivalent (MET)·min·week^-1 (HR=1.24, 95%CI: 1.06‒1.44), substandard of HbA1c control (HR=1.16, 95%CI: 1.03‒1.30), occasional smoker(HR=1.23, 95%CI: 1.04‒1.45), and those who took insulin therapy (HR=1.36, 95%CI: 1.11‒1.66) were associated with an increased risk of stroke, while those received contracted services from family doctors were associated with a decreased risk of stroke(HR=0.78, 95%CI: 0.71‒0.88). ConclusionCommunity T2DM population in Shanghai has a high risk of stroke. It is necessary to continue to explore the positive role of family doctor contract service management model, strengthen individualized exercise, smoking cessation and other lifestyle interventions, and strictly control blood glucose as soon as one can to delay or avoid the occurrence of complications.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Objective:To investigate altered neurovascular coupling in patients with depression(DEP)using resting-state functional magnetic resonance imaging(MRI)and arterial spin labeling perfusion MRI,as well as its association with depressive symptoms.Methods:Neuropsychological assessment and multimodal MRI scans were performed for 25 DEP patients and 35 healthy controls(HCs).Arterial spin labeling perfusion MRI was used to calculate cerebral blood flow(CBF),and functional MRI was used to calculate regional homogeneity(ReHo).The Pearson correlation coefficient between CBF and ReHo was calculated to obtain neurovascular cou-pling.Results:At the whole-brain level,CBF-ReHo coupling was reduced in DEP patients compared with HCs.At the brain region level,CBF-ReHo coupling was reduced in 26 brain regions in DEP patients,which were mainly located in the visual network,the default network,and the auditory network.The correlation analysis showed that the coupling values of the left suboccipital gyrus,the left angular gyrus,and the left thalamus were negatively correlated with Hamilton Depression Scale score.Conclusion:There is a sig-nificant reduction in neurovascular coupling in DEP patients,which is correlated with the severity of DEP.

Purpose/Significance By integrating clinical and biological sample information,a big data research platform for biologi-cal sample information resources is built to provide one-stop data retrieval,integration and analysis services for researchers,and a data governance system is established,so as to improve the level of hospital clinical research infrastructure construction.Method/Process Common data model and data governance technology are adopted to integrate data sources from different vendors through extraction,trans-formation,loading and other steps to provide a unified data access portal.Result/Conclusion The big data research platform for biologi-cal sample information resources has the advantages of multi-dimensional data screening and rapid integrated analysis,which can pro-vide support for clinical research.

OBJECTIVE To evaluate the effectiveness and safety of sequential therapy with parathyroid hormone analogues and bisphosphonates for osteoporosis. METHODS PubMed， Embase， the Cochrane Library， Web of Science， China National Knowledge Infrastructure， VIP， Wanfang data， and SinoMed were searched in both English and Chinese databases from their inception to March 25， 2024. Two researchers independently conducted literature searches， screening， and data extraction. Review Manager 5.4 software was used for the meta-analysis. Subgroup analyses and sensitivity analyses were performed based on different medication sequences in the treatment group to account for potential sources of heterogeneity. RESULTS A total of 7 randomized controlled trials involving 2 461 participants were included， with 1 215 in the treatment group and 1 246 in the control group. The meta-analysis results showed that the treatment group using sequential therapy with parathyroid hormone analogues and bisphosphonates had superior effects on improving bone mineral density at the lumbar spine [SMD＝0.90， 95%CI （0.44， 1.35）， P＜0.001]， total hip [SMD=0.68， 95%CI （0.14， 1.21）， P＝0.01]， and femoral neck [SMD＝0.45， 95%CI （0.04， 0.86）， P＝0.03] compared to the control group. It also significantly outperformed the control group in reducing the incidence of fractures post- treatment [OR＝0.72， 95%CI （0.54， 0.97）， P＝0.03].significant difference was noted in the incidence of adverse reactions between the two groups [OR＝1.21， 95%CI （0.99， 1.46）， P＝0.06]. Subgroup analysis based on intervention measures in the treatment group showed that switching from bisphosphonates to parathyroid hormone analogues [SMD＝0.56， 95%CI （0.09， 1.03）， P＝0.02] or switching from parathyroid hormone analogues to bisphosphonates [SMD＝0.97， 95%CI （0.49， 1.46）， P＜0.001] both significantly potentiated lumbar spine bone mineral density compared to the control group. Switching from bisphosphonates to parathyroid hormone analogues also significantly promoted total hip bone mineral density compared to the control group [SMD＝0.66， 95%CI （0.18， 1.13）， P＝0.007]. Sensitivity analysis indicated that the results of this study were robust. CONCLUSIONS Sequential therapy with parathyroid hormone analogues and bisphosphonates can be recommended as an effective treatment for patients with osteoporosis， with good safety profiles. The medication sequences should be individually adjusted based on the patient’s particular situation and the different responses of various skeletal sites.

ObjectiveTo investigate the effect of shikosin （SHI） on psoriasis （PSO） and explore the underlying mechanism via the cyclic guanosine monophosphate-adenosine monophosphate synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodHaCaT cells were classified into normal culture（Control）， a mixture of five proinflammatory cytokines（M5）， low-， medium-， and high-dose SHI （L-SHI， M-SHI， and H-SHI， respectively）， and SHI+ADU-S100 groups. The cells in the M5 group were stimulated with 10 μg·L^-1 interleukin （IL）-1α， IL-17， IL-22， tumor necrosis factor （TNF）-α， and oncostatin M （OSM） for 48 h. The cells in the L-SHI， M-SHI， and H-SHI groups were treated with 0.1， 1， 10 μmol·L^-1 SHI， respectively， on the basis of the treatment in the M5 group. The cells in the SHI+ADU-S100 group were treated with 10 μmol·L^-1 STING activator ADU-S100 on the basis of the treatment in the H-SHI group. The methyl thiazolyl tetrazolium （MTT） assay and colony formation assay were employed to examine the effect of SHI on the proliferation of HaCaT cells. The wound healing assay was employed to examine the effect of SHI on the migration of HaCaT cells. Flow cytometry was employed to detect the effect of SHI on the apoptosis of HaCaT cells. Enzyme-linked immunosorbent assay was employed to measure the levels of IL-1β， IL-6， IL-15， IL-23， and interferon-γ （IFN-γ） in HaCaT cells. Western blot was employed to determine the protein levels of cGAS and STING in HaCaT cells. ResultCompared with Control group， the M5 group showed decreased survival rate， colony formation， and would healing rate of HaCaT cells， increased apoptosis rate， elevated levels of IL-1β， IL-6， IL-15， IL-23， and IFN-γ， and up-regulated protein levels of cGAS and STING （P<0.01）. Compared with the M5 group， the L-SHI， M-SHI， and H-SHI groups showed increased survival rate， cell colony formation， and wound healing rate， decreased apoptosis rate， lowered levels of IL-1β， IL-6， IL-15， IL-23， and IFN-γ， and down-regulated protein levels of cGAS and STING （P<0.01）. Compared with the H-SHI group， the SHI+ADU-S100 group showed decreased survival rate， cell colony formation， and wound healing rate， increased apoptosis rate， risen levels of IL-1β， IL-6， IL-15， IL-23， and IFN-γ， and up-regulated protein levels of cGAS and STING （P<0.01）. ConclusionSHI can inhibit the inflammation in the cell model of PSO by inhibiting the cGAS/STING signaling pathway.

National health standards involve all kinds of technical requirements formulated and numbered in accordance with the procedures and formats stipulated in the standardisation system for the implementation of national health and hygiene laws, regulations and policies, and the protection of human health. The establishment of health standards in China should align with our legal framework, including laws, regulations, departmental rules, and health and hygiene policies. During the development of these standards, a comprehensive approach is advocated, encompassing in-depth investigations, rigorous demonstrations, and extensive stakeholder engagement. However, the process of standard formulation may suffer from insufficient research evidence. The evidence-based concept emphasizes the significance of evidence. Therefore, integrating evidence-based concept into the process of developing health standards can enhance the quality and scientific basis of these standards. This article systematically elucidates the current status and development process of health standards in China, explores the necessity and feasibility of incorporating evidence-based concept into the development of these standards, analyzes the challenges and opportunities, and presents reflections and suggestions.