BACKGROUND:Bone morphogenetic protein 7 is mainly synthesized in the kidney and is expressed at different stages of kidney development,but the spatiotemporal distribution of its expression and its relationship with kidney development have not been systematically reported.OBJECTIVE:To observe the expression of bone morphogenetic protein 7 in mice kidneys during different developmental stages and to explore its potential relationship with kidney development.METHODS:Immunohistochemical techniques combined with stereological methods and western blot analysis were used to observe and analyze the expression of bone morphogenetic protein 7 in mouse kidney tissues at embryonic days(E)12,14,16,18,and neonatal days(N)1,3,7,14,24,40,and 70.RESULTS AND CONCLUSION:(1)The results of immunohistochemistry showed that bone morphogenetic protein 7 was mainly expressed in the nephrogenic zone and immature renal corpuscles during the early stage of kidney development.Subsequently,it was located in mature renal corpuscles and the surrounding distal convoluted tubules,and the expression range gradually increased.After N40 days,bone morphogenetic protein 7 positively expressed in the renal interstitium.(2)Stereology and western blot results showed that the expression level of bone morphogenetic protein 7 gradually decreased with the development of the kidney,reached the lowest level at N7 days,and then slowly increased.To conclude,during the process of kidney development,the expression of bone morphogenetic protein 7 has significant spatiotemporal specificity,and it is hypothesized that it may be related to the development and maturation of renal corpuscles and distal convoluted tubules.

OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

BACKGROUND:Bone morphogenetic protein 7 is mainly synthesized in the kidney and is expressed at different stages of kidney development,but the spatiotemporal distribution of its expression and its relationship with kidney development have not been systematically reported.OBJECTIVE:To observe the expression of bone morphogenetic protein 7 in mice kidneys during different developmental stages and to explore its potential relationship with kidney development.METHODS:Immunohistochemical techniques combined with stereological methods and western blot analysis were used to observe and analyze the expression of bone morphogenetic protein 7 in mouse kidney tissues at embryonic days(E)12,14,16,18,and neonatal days(N)1,3,7,14,24,40,and 70.RESULTS AND CONCLUSION:(1)The results of immunohistochemistry showed that bone morphogenetic protein 7 was mainly expressed in the nephrogenic zone and immature renal corpuscles during the early stage of kidney development.Subsequently,it was located in mature renal corpuscles and the surrounding distal convoluted tubules,and the expression range gradually increased.After N40 days,bone morphogenetic protein 7 positively expressed in the renal interstitium.(2)Stereology and western blot results showed that the expression level of bone morphogenetic protein 7 gradually decreased with the development of the kidney,reached the lowest level at N7 days,and then slowly increased.To conclude,during the process of kidney development,the expression of bone morphogenetic protein 7 has significant spatiotemporal specificity,and it is hypothesized that it may be related to the development and maturation of renal corpuscles and distal convoluted tubules.

Lung cancer has the highest mortality rate among malignant tumors worldwide, posing a severe threat to human health. Traditional Chinese medicine (TCM) offers unique advantages in treating lung cancer, with disease-syndrome-integrated animal models serving as a critical component of TCM lung cancer research. According to TCM pathogenesis, lung cancer is classified as a pattern of underlying deficiency with superficial excess. Clinically, it is often categorized into syndromes such as qi and yin deficiency, lung-spleen qi deficiency, lung yin deficiency, qi stagnation and blood stasis, and phlegm-heat obstructing the lungs. Treatment should fundamentally adhere to the principle of "strengthening the healthy qi and expelling pathogenic factors". This paper systematically reviews literature from 2005 to 2025 on disease-syndrome-integrated animal models for lung cancer. It summarizes the theoretical basis and establishment methods of four core disease-syndrome-integrated models: qi-yin deficiency pattern, spleen qi deficiency pattern, qi stagnation and blood stasis pattern, and kidney deficiency pattern. Further discussion covers their evaluation systems and limitations. Additionally, modeling approaches for other patterns including yang deficiency, spleen deficiency, and qi deficiency with blood stasis are summarized, with evaluation methods categorized by behavioral characteristics and biochemical indicators. Analysis reveals that current models predominantly use C57BL/6 mice, exhibiting issues such as insufficient clinical relevance, complex modeling procedures, numerous confounding factors, and a low degree of standardization. Future improvements to disease-syndrome-integrated lung cancer animal models could include using clustered regularly interspaced short palindromic repeats (CRISPR) technology to establish organoid–patient-derived xenograft models; developing controllable composite stress systems and standardized stimulus models, such as gradient-controlled alternating cold/heat chambers and programmed dietary regulation systems, to reduce nonspecific interference; and developing multidimensional dynamic modeling techniques by integrating clinical big data, including metabolomics and imaging features, to design dynamic intervention protocols, thereby providing more precise and reliable experimental tools for elucidating the mechanisms of TCM in lung cancer prevention and treatment.

Objective:To explore the current status and factors influencing physical activity among pre-frail and frail older adults in the community.Methods:Convenience sampling was used to select 207 pre-frail and frail older adults from Donghuashi community and Fangzhuang community in Beijing from April to June 2024 as study subjects. Older adults were surveyed for their general information, lifestyle behaviors, nutritional status, and physical activity. Binary Logistic regression was used to explore the factors influencing the level of physical activity among pre-frail and frail older adults in the community.Results:A total of 207 questionnaires were distributed and 204 valid questionnaires were recovered, with a valid recovery rate of 98.55%. The Physical Activity Scale for the Elderly score of the 204 community-based pre-frail and frail older adults was 86.87 (52.14, 125.00), and the form of activity was predominantly walking (98.5%, 201/204) and light domestic physical activity (85.8%, 175/204). Binary Logistic regression showed that taking a nap ( OR=3.614), abnormal nighttime sleep duration ( OR=4.077), fear of falling before or during exercise ( OR=7.895), and risk of malnutrition ( OR=9.263) were risk factors for levels of physical activity in pre-frail and frail older adults in the community ( P<0.05), and good exercise cognition ( OR=0.055) was a protective factor for physical activity levels ( P<0.05) . Conclusions:Pre-frail and frail older adults in the community have low levels of physical activity, which is dominated by walking and household activities. Community healthcare workers should strengthen the management of physical activity for pre-frail and frail older adults, cultivate their good living habits, improve their sleep quality, ensure sufficient night sleep, help them overcome the fear of falling before or during exercise, set up the correct concept of exercise, form a good cognition of exercise, and guide their family members to pay attention to the nutritional status of older adults, beware of the risk of malnutrition, and improve the level of physical activity to delay or even reverse the frail state.

Objective:To investigate the current status of physical function decline among community-dwelling elderly in Beijing and analyze its influencing factors.Methods:A convenience sampling method was used to select elderly individuals from Fangzhuang Community in Fengtai District and Donghuashi Community in Dongcheng District, Beijing, between February and July 2023. Data were collected using a general information questionnaire, lifestyle behavior survey, Mini-Mental State Examination (MMSE), and the Short Physical Performance Battery (SPPB). Binary Logistic regression analysis was performed to identify factors influencing physical function decline.Results:A total of 2 434 questionnaires were distributed, with 2 060 valid responses, yielding an effective response rate of 84.6%. Among the 2 060 community-dwelling elderly, 1 273 exhibited physical function decline. Logistic regression analysis revealed that age, history of stroke, alcohol consumption, annual physical examinations, social participation frequency, and cognitive impairment were significant factors influencing physical function decline among community-dwelling elderly ( P<0.05) . Conclusions:Physical function decline is prevalent among community-dwelling elderly in Beijing. Regular physical examinations, active social participation, early rehabilitation of stroke, and early screening and intervention for cognitive impairment can help slow the progression of physical function decline.

Objective:Based on the health ecological model, this study aimed to identify the influencing factors of cognitive function in older patients with common cardiovascular diseases in China, providing insights for the prevention of cognitive impairment in this population.Methods:A multi-stage sampling method was used to recruit 9 833 older patients with common cardiovascular diseases from ten ClassⅢ Grade A hospitals located in North China, East China, Central-South China, Southwest China, and Northwest China between January and December 2023. General information and cognitive status were assessed using a self-designed Ceneral Information Questionnaire and the Mini-mental State Examination. Binary Logistic regression was applied to explore factors influencing cognitive function.Results:Among the 9 833 patients, 2 394 (24.3%, 2 394/9 833) were identified with cognitive impairment. Binary Logistic regression analysis showed that intrapersonal level (gender, age, physical function, history of stroke, and history of chronic obstructive pulmonary disease), behavioral level (social activity participation and regular exercise), interpersonal network level (marital status and self-reported social support), and living and working conditions level (educational level, per capita monthly household income, and type of residence area) were the influencing factors of cognitive function ( P<0.05) . Conclusions:Cognitive function in older adults with cardiovascular diseases is suboptimal and influenced by multi-level and multidimensional factors. Healthcare providers should focus on monitoring high-risk individuals and promoting social participation and regular physical activity among this population.

Objective To investigate the association between 8 insulin resistance(IR)surrogate markers and incident atherosclerotic cardiovascular disease(ASCVD)in population with cardiovascular-kidney-metabolic syndrome(CKM)of stages 0-3,and to identify the surrogate marker with the best predictive performance.Methods A study was conducted on 20121 community residents classified as CKM stages 0-3 from the Chengdu cohort of the China Multi-Ethic Cohort.A Cox proportional hazards model was used to calculate hazard ratios(HRs)between each IR surrogate marker and incident ASCVD.Cubic spline regression was employed to explore the dose-response relationships between these markers and incident ASCVD.The relative relationships between different markers and incident ASCVD were examined through the ratio of HRs(RHRs).Time-dependent area under the receiver operating characteristic curve(TDAUC)and Uno's C-statistic were calculated to compare the predictive performance of each marker for incident ASCVD.Based on the PREVENT equation components and the 8 surrogate markers under analysis,random forest feature selection was used to determine the contribution of each marker to accurate prediction.Results During a follow-up period of82 741.93 person-years,1447 incident cases of ASCVD were recorded,with an incidence density of 17.49 per 1000 person-years.Association analyses indicated that the triglyceride to high-density lipoprotein cholesterol ratio(TG/HDL)and the TyG/(TG/HDL)index were not associated with incident ASCVD(P＞0.05).The TyG index combined with obesity measurement parameters emerged as a reliable predictor of ASCVD incidence.The most promising indicator,TyG index with waist-to-height ratio(TyG_WHtR),exhibited an inverted J-shaped association with incident ASCVD(P for nonlinearity=0.045;TDAUC=0.640;C=0.634),while the TyG index with body mass index(TyG_BMI),waist circumference(TyG_WC),and waist-to-hip ratio(TyG_WHR)showed positive linear associations(all P for trend＜0.05),with relatively lower predictive performance(C=0.564,0.588,and 0.598,respectively).Although both the TyG index and the metabolic score for insulin resistance(METS-IR)were associated with increased ASCVD risk(TyG:Q2 vs.Q1,HR=1.23 and Q4 vs.Q1,HR=1.24;METS-IR:P for non-linearity=0.045),they exhibited poor predictive performance for incident ASCVD.Conclusion The TyG index combined with obesity measurement parameters is an ideal IR surrogate marker for predicting incident ASCVD in populations with stages 0-3 CKM.Monitoring these markers will facilitate the prevention and control of cardiovascular diseases in CKM populations.

Siwu Decoction is a classic formula for tonifying the blood and activating blood circulation and is characterized by its ability to tonify the blood without leaving stasis and promote blood circulation without harming the vital energy of the body.It is widely used in clinical practice for the treatment of various conditions related to blood deficiency and poor blood circulation,such as anemia,menstrual disorders,and dysmenorrhea.The liver is responsible for governing the free flow of Qi and storing blood,and abnormalities in liver function are associated with various acute and chronic liver injuries.Siwu Decoction can restore liver homeostasis by tonifying the blood,activating blood circulation,nourishing the blood,and soothing the liver.Based on its unique prescription formulation and multiple pharmacological mechanisms,Siwu Decoction has become an important prescription for enhancing liver microcirculation,facilitating hepatocyte repair and regeneration,and alleviating liver injury.This article reviews the effect and mechanism of Siwu Decoction in the prevention and treatment of various liver injuries(including alcoholic liver disease,nonalcoholic fatty liver disease,nonalcoholic fatty liver disease,liver fibrosis,and liver cirrhosis)and discusses existing problems and future research directions.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans