BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

ObjectiveTo explore the relationship between self-assessed health and age-adjusted Charlson comorbidity index （AICC） in older adults， and to further analyze the differences in this relationship across gender groups. MethodsBased on the China health and retirement longitudinal study （CHARLS） database， this study selected data on basic characteristics， chronic disease status， depressive symptoms， and self-assessed health of older adults aged ≥60 years. Chi-square tests were used to perform a preliminary analysis of the association between these factors and AICC scores. A multifactorial ordered logistic regression model was constructed to assess the effects of each influencing factor on AICC， while multiple linear regression analysis was used to explore the linear relationship between self-rated health and AICC scores. Additionally. Stratified analysis by gender was performed to evaluate gender differences. ResultsA total of 10 911 participants were included， with a mean age of 67.40±5.94 years； 6 249 （57.3%） were male and 4 662（42.7%） were female. The distribution of AICC scores was categorized into low-risk， moderate-risk， higher-risk， and high-risk groups， accounting for 23.5%， 50.2%， 20.6%， and 5.7%， respectively. Multifactorial logistic regression analysis revealed that self-rated health was negatively associated with AICC in the total population and in the male geriatric group （OR=0.843， 95% CI： 0.776， 0.917， P=0.001）， （OR=0.886， 95% CI： 0.796 ， 0.987， P=0.028）， but did not reach statistical significance in the female geriatric group . Linear regression analysis further indicated a significant negative linear relationship between self-rated health and AICC （b=-0.485， 95% CI： -0.516，-0.455， P＜0.001）.This relationship was consistent in both male （b=-0.356， 95% CI： -0.406，-0.305， P＜0.001） and female （b=-0.373， 95% CI： -0.435，-0.310， P＜0.001） subgroups， with a stronger negative association in females. ConclusionSelf-rated health is significantly negatively associated with AICC， and attention should be given to self-rated health in the female geriatric population. Self-rated health can serve as an important tool for identifying elderly group at high risk of comorbidities providing a valuable basis for precise intervention.

ObjectiveTo observe the effect of water extract of Mori Folium （MLE） on oxidative stress in adipose tissue of type 2 diabetes mellitus （T2DM） mice and explore its mechanism. MethodTwenty-four male db/db mice were randomly divided into model group， metformin group， low-dose MLE （MLE-L） group， and high-dose MLE （MLE-H） group according to their body weight and blood glucose， with six mice in each group， and other six C57BLKS/JGpt wild littermate mice were selected as normal group. The mice in the metformin group were given 200 mg·kg^-1 metformin suspension， and the mice in the MLE-L and MLE-H groups were respectively given 2 g·kg^-1 and 4 g·kg^-1 MLE， while the mice in the normal group and model group were given the same dose of deionized water by daily gavage for eight weeks. Body weight， subcutaneous fat index， fasting blood glucose （FBG）， and oral glucose tolerance level （OGTT） of the mice were detected， and serum superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and malondialdehyde （MDA） were measured. The expression levels of silent information regulator 1 （SIRT1） and NADPH oxidase type 4 （NOX4） protein in subcutaneous adipose tissue of the mice were detected by Western blot. ResultThe FBG level， OGTT， and subcutaneous fat index of T2DM mice were significantly decreased （P<0.05， P<0.01） after administration of MLE compared with the blank group. The contents of serum SOD and GSH were significantly increased， while the level of oxidative stress damage marker MDA was significantly decreased （P<0.05， P<0.01）. The expression of SIRT1 protein in adipose tissue was significantly increased， while the expression of NOX4 protein was significantly decreased （P<0.05， P<0.01）. ConclusionMLE can ameliorate T2DM by alleviating oxidative stress in adipose tissue of T2DM mice and reducing blood glucose.

ObjectiveTo investigate the protective effects of Mori Folium extract （MLE） on the kidney of db/db diabetic mice and its mechanism. MethodTwenty-four male C57BLKS/JGpt-Leprdb/Leprdb （db/db） mice were randomly divided into model group， metformin group， low-dose group of MLE （MLE-L）， and high-dose group of MLE （MLE-H） according to their fasting blood glucose （FBG）， with six mice in each group， and other six C57BLKS/JGpt wild littermate （m/m） mice were selected as normal group. The mice in the drug administration groups were given corresponding drugs by gavage， and the mice in the normal group and model group were given the same dose of deionized water by gavage once a day for continuous eight weeks. Body weight， bilateral kidney weight， and FBG were measured， and an oral glucose tolerance test （OGTT） was performed. The pathological changes in the kidney tissue of mice were observed by hematoxylin-eosin （HE） and periodic acid-silver （PAS） staining， and serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of tumor necrosis factor-alpha （TNF-α） and interleukin-6 （IL-6） in serum and urinary microalbumin （U-mAlb） of mice. The expression levels of toll-like receptor 4 （TLR4）， myeloid differentiation factor 88 （MyD88）， and nuclear factor-kappa B p65 （NF-κB p65） protein in kidney tissue of mice were tested by Western blot. ResultCompared with the normal group， the body weight， absolute renal weight， FBG， and the area under the curve （AUC） of OGTT of mice in the model group were significantly increased （P<0.01）， and the levels of SCr， BUN， and U-mAlb， as well as TNF-α and IL-6 in serum were significantly increased （P<0.01）. The glomerular basement membrane in the kidney tissue of mice was thicker， with obvious inflammatory cell infiltration. The protein expression levels of TLR4， MyD88， and NF-κB p65 in the kidney tissue of mice were increased significantly （P<0.01）. Compared with the model group， there was no statistical difference in the body weight of mice in each drug administration group. The absolute renal weight of mice in the MLE-H and metformin groups was significantly reduced （P<0.05， P<0.01）. The FBG levels of mice in the metformin， MLE-L， and MLE-H groups started to decrease after treatment for four to eight weeks （P<0.05， P<0.01）. The AUC of mice in the MLE-H and metformin groups was significantly decreased （P<0.01）. The levels of SCr， BUN， and U-mAlb of mice in the MLE-H and metformin groups were significantly decreased （P<0.01）， and those of SCr and U-mAlb of mice in the MLE-L group were significantly decreased （P<0.01）. The levels of TNF-α and IL-6 in the serum of mice in the MLE-H and metformin groups were significantly decreased （P<0.01）. The renal tissue pathology of mice in each drug administration group was improved to varying degrees， and the protein expression levels of TLR4， MyD88， and NF-κB p65 in the MLE-H group were decreased significantly （P<0.05， P<0.01）. ConclusionMLE can improve the renal structure and function of db/db diabetic mice， and its mechanism may be related to the inhibition of the TLR4/MyD88/NF-κB signaling pathway.

Mori Folium， the dried leaves of Morus alba， is widely used in clinical practice for dispersing wind and heat， clearing the lung and moistening dryness， soothing the liver and improving vision， and cooling blood and stopping bleeding. It has been used to regulate blood glucose since ancient times， and modern studies have shown that the active components of Mori Folium for lowering blood glucose mainly include flavonoids， alkaloids， polysaccharides， and phenols. These components are mainly extracted by solvents such as water and alcohols with the assistance of ultrasound and microwave. In addition， new extraction methods are emerging， such as CO₂ supercritical fluid extraction， enzymatic hydrolysis， and cloud point extraction. Mori Folium lowers blood glucose via multiple components， pathways， and targets. Specifically， it can improve glucose and lipid metabolism， protect pancreatic β cells， and alleviate insulin resistance to reduce the damage caused by hyperglycemia and restore normal physiological functions. Although a large number of studies have been carried out on diabetes， the causes and radical treatment methods remain to be explored， and diabetes is still a major disease that endangers human health and needs to be solved urgently. The articles about extraction process and mechanism of active components in Mori Folium for lowering blood glucose were retrieved from the China National Knowledge Infrastructure （CNKI）， Web of Science， and PubMed. We analyzed the applicable extraction methods for the blood glucose-lowering components such as flavonoids， polysaccharides， and alkaloids in Mori Folium， and compared the conventional and emerging methods. Furthermore， we summarized our research achievements in the extraction of active components from Mori Folium and the blood glucose-lowering effect and mechanisms. This review aims to provide theoretical support for the optimization of the extraction process， the research on the blood glucose-lowering components and mechanism， and the development of new drugs and clinical application of Mori Folium.

ObjectiveTo investigate the current situation of health communication carried out by medical institutions in Shanghai through new media platforms such as WeChat， Weibo， Toutiao， Douyin， Kuaishou， Bilibili and WeChat Videos， and to propose targeted measures. MethodsBased on the systematic collection of new media accounts of medical institutions in Shanghai， and through the combination of keyword screening and manual audit， health communication data of medical institutions on new media platforms were determined. ResultsData from 1 117 new media accounts of 162 medical institutions in Shanghai were collected， including 610 WeChat official accounts， 105 WeChat video accounts， 89 Weibo accounts， 18 Bilibili accounts， 198 Douyin accounts， 37 Toutiao accounts， and 60 Kuaishou accounts， totaling 111 853 posts. After keyword sorting and manual screening， a total of 66 761 health science posts were collected， with WeChat Official Accounts， Douyin， and Weibo having the top three highest number of posts. Video-based new media such as Douyin， WeChat Videos， Kuaishou， and Bilibili had a better communication impact than text and image-based new media like WeChat Official Accounts， Weibo， and Toutiao. Among them， Douyin and Toutiao were the best platforms for video and text-image-based new media， respectively. ConclusionMedical institutions in Shanghai recognize the importance of new media in health communication and have made full use of various media platforms to carry out health communication，having a certain impact on health education. In the future， medical institutions should choose appropriate platforms based on target audiences and content characteristics， fully leverage the advantages of various platforms， explore innovative communication strategies， promote the dissemination of health knowledge， and enhance the health literacy of the public.

As people's living standards improve， the development trend of diabetes has gradually become severe. Diabetes is a chronic inflammatory disease associated with abnormal expression of nuclear factor-kappa B （NF-κB） in patients. NF-κB exists in various tissue cells and participates in the regulation of a variety of genes related to immune function and inflammation. Varieties of factors can activate NF-κB when the body is stimulated by external factors， so as to produce inflammation and other reactions. Previous studies on NF-κB mainly focus on cancer， and the pathological mechanism of the treatment of diabetes by related signaling pathways and the progress of traditional Chinese medicine （TCM） treatment have not been systematically elaborated on. By referring to the relevant literature in China and abroad， it was found that NF-κB is not isolated in the development and progression of diabetes but is associated with signal molecules related to inflammation， oxidative stress， and energy metabolism， and it is involved in mediating inflammation， pancreatic β cell apoptosis， insulin signal transduction， and other physiological functions. Therefore， blocking the transmission of NF-κB signaling pathway is beneficial to the treatment of diabetes. At present， Western medicine for the treatment of diabetes mainly includes oral hypoglycemic drugs and insulin injections， but the adverse reactions are obvious. TCM has been characterized by multi-target， extensive action， and excellent curative effects in the treatment of diabetes. TCM and its compounds with functions of tonifying Qi and promoting blood circulation， regulating qi and eliminating phlegm， clearing heat and detoxifying， and nourishing Yin and moistening dryness can effectively intervene in the abnormal expression of NF-κB signaling pathway in vivo through anti-inflammatory effects. In this paper， the association between NF-κB signaling pathway and diabetes was summarized， and the modern research progress of TCM intervention of NF-κB signaling pathway in the treatment of diabetes in the past five years was reviewed， so as to lay a laboratory foundation for the study of a new pathological mechanism of diabetes based on NF-κB signaling pathway and provide new targets and research direction for the prevention and treatment of diabetes and development of related TCM.

ObjectiveTo observe the effect of earthworm protein on the expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor E₂-related factor 2 （PI3K/Akt/Nrf2） pathway in the aorta of spontaneously hypertensive rats （SHR） and explore mechanism of earthworm protein in treating hypertensive vascular endothelial dysfunction （VED）. MethodTen 10-week-old Wistar Kyoto （WKY） rats and fifty SHR rats were selected for a week of adaptive feeding. WKY rats were selected as the normal group， and fifty SHR rats were randomized according to body weight into model， valsartan （8×10^-3 g·kg^-1·d^-1）， and high-， medium-， and low-dose （0.2， 0.1， 0.05 g·kg^-1·d^-1， respectively） earthworm protein groups. The normal and model groups were administrated with equal volume of double distilled water by gavage. During the drug intervention period， the general situations of rats in each group were observed and their blood pressure was monitored at specific time points every other week before and after administration. After 8 weeks of drug intervention， enzyme-linked immunosorbent assay was employed to measure the levels of angiotensin-Ⅱ （Ang-Ⅱ） and endothelin-1 （ET-1） in the serum of rats in each group. The corresponding kits were used to determine the levels of nitric oxide （NO）， malondialdehyde （MDA）， glutathione peroxidase （GPX）， superoxide dismutase （SOD）， and ferrous ion （Fe²⁺）. Hematoxylin-eosin （HE） staining was employed to observe the changes in the intima of the aorta. Fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA levels of PI3K， Akt， Nrf2， heme oxygenase-1 （HO-1）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Western blotting was used to determine the protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the thoracic aorta. ResultCompared with the normal group， the model group had decreased body mass， increased irritability， severe endothelial damage， elevated blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe²⁺ （P<0.01）， lowered NO level （P<0.01）， and down-regulated mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the aortic tissue （P<0.01）. Compared with the model group， drug intervention caused no significant change in the body mass， calmed the rats， alleviated the endothelial damage， lowered blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe²⁺ （P<0.01）， elevated the NO level （P<0.05）， and up-regulated the mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 （P<0.05）. ConclusionThe earthworm protein can exert antihypertensive effects by ameliorating VED in SHR. Specifically， it may regulate the PI3K/Akt/Nrf2 signaling pathway to inhibit oxidative stress and ferroptosis.

Diabetic peripheral neuropathy is a common diabetic complication.Presently,our understanding of its pathogenesis is incomplete,and there are no effective treatment options.In-depth research requires the use of animal experiments.The criteria for modeling success and the evaluation method for peripheral nerve function recovery are critical for carrying out animal experiments into type 2 diabetic peripheral neuropathy.However,but there has been a lack of systematic interrogation and analysis of the evaluation method used with type 2 diabetic peripheral neuropathy models.Therefore,the author reviewed the recent data,summarized and analyzed the evaluation method used for animal models of type 2 diabetic peripheral neuropathy of small and large nerve fibers,and proposed future directions for development,providing a reference for related research.

ObjectiveTo compare the development status of health facilities in different regions （non-agricultural and agricultural districts）and different types across four dimensions： organizational management， health environment， health activities， and health outcomes， to explore factors that may affect the current development status and summarize effective experiences， and to provide a foundation for the subsequent comprehensive， standardized， and effective promotion of health facility development and tiered and classified management. MethodsInvestigators conducted a health status survey based on the four dimensions for 50 health facilities in 16 districts of Shanghai， representing three types （including government agencies， enterprises， and communities）. Evaluation forms were filled out through on-site observation and document reviews， which were developed in accordance with the Shanghai Health Settings Evaluation Standards （for trial implementation in 2019）. ResultsThe average total score of health facilities in Shanghai was （88.42±11.93） points， with an overall excellence rate of 86.0%. The excellence rate of each dimension， from highest to lowest， were healthy environment （84.0%）， organizational management （82.0%）， health activities （78.0%）， and health outcomes （44.0%）. Health facilities in agricultural districts scored higher in both total score and average score on the organizational management dimension compared to non-agricultural districts. The excellence rate for the organizational management dimension was also higher in agricultural districts than in non-agricultural districts. There was no statistical significance in the total score， the score of each dimension， the overall excellence rate， and the excellence rate of each dimension among different types of health facilities （P>0.05）. ConclusionThe development of health facilities among government agencies， enterprises， and communities in Shanghai has begun to yield positive results. Health facilities in non-agricultural districts should actively draw on the experience of those in agricultural districts， particularly in organizational management， adjust development ideas and planning based on their own realities， so as to continuously improve the levels of development.