Objective To identify factors affecting and key environmental factors of the Oncomelania hupensis snail density in the Yangtze River Delta region using machine learning methods. Methods Administrative village-level O. hupensis snail survey data in the Yangtze River Delta (including Shanghai Municipality, Jiangsu Province, Zhejiang Province and Anhui Province) from 2011 to 2021 were retrieved from the Information Management System for Parasitic Disease Control of Chinese Center for Disease Control and Prevention. Environmental factor data were captured from the Google Earth Engine platform, including elevation, slope, terrain, normalized difference vegetation index (NDVI), vegetation type, soil type, total petroleum hydrocarbon (TPH), ammonium nitrogen, inorganic nitrogen, dissolved oxygen, pH of water, chemical oxygen demand (COD) and inorganic phosphorus, and climatic factor data in the study region were retrieved from the Copernicus Climate Data Store, including annual precipitation, aridity index and annual mean temperature (AMT). O. hupensis snail survey data in the Yangtze River Delta region from 2011 to 2021 were randomly divided into a training set (70%) and a test set (30%), and five machine learning models were selected for machine learning model construction and comparative analysis of the O. hupensis snail density using the software R 4.3.0, including random forest (RF), eXtreme gradient boosting (XGBoost), support vector machine (SVM), gradient boosting machine (GBM) and neural network (NN). The XGBoost model was employed to construct a predictive model for the O. hupensis snail density, and the impact of each environmental factor on O. hupensis snail distribution was quantified. The SHapley Additive exPlanations (SHAPs) values were calculated to estimate the average contribution of each variable to the model prediction, and the core environmental factors affecting the O. hupensis snail population density were screened. Results Among the five machine learning models, the XGBoost model exhibited the optimal comprehensive performance, with the coefficient of determination (R²) of 0.855, mean squared error (MSE) of 0.188, root mean squared error (RMSE) of 0.434 and mean absolute error (MAE) of 0.155, respectively. Analysis of factors affecting the O. hupensis snail density with the XGBoost model showed that among the 16 environmental factors, the top four high-impact factors ranked by SHAPs values included annual precipitation, elevation, aridity index and NDVI, with cumulative SHAPs contributions of 75%, which was higher than that of other environmental factors. If NDVI was higher than 0.6, the O. hupensis snail density increased with NDVI and peaked if NDVI was 0.8 (1.60 snails/0.1 m²). The O. hupensis snail density increased with elevation if the elevation ranged from 14 to 40 m, and slowly rose if the annual precipitation ranged from 900 to 1 300 mm, and then increased rapidly to the peak (1.52 snails/0.1 m²) if the annual precipitation ranged from 1 300 to 1 500 mm. In addition, the O. hupensis snail density increased rapidly to the maximum (1.60 snails/0.1 m²) if the aridity index ranged from 0.8 to 1.1, and decreased gradually if the aridity index exceeded 1.1. Conclusions The XGBoost model shows excellent performance in prediction of the O. hupensis snail density and identification of key environmental factors in the Yangtze River Delta region. Annual precipitation, elevation, aridity index and NDVI are key environmental factors affecting the distribution and density of O. hupensis snails in the Yangtze River Delta region.

ObjectiveThe exacerbating trend of global population aging poses profound socioeconomic and public health challenges, making the comprehensive elucidation of biological aging mechanisms and the discovery of effective anti-aging interventions an urgent priority in the life sciences. Based on our previous serum metabolomics findings that dimethylglycine, an intermediate metabolite of amino acid metabolism naturally present in the human body, was significantly enriched in the serum of longevity families, this study aimed to systematically investigate the anti-aging effects of dimethylglycine both in living organisms and in controlled laboratory environments, and to preliminarily elucidate its underlying molecular mechanisms. While existing literature indicates that dimethylglycine possesses antioxidant and immunomodulatory properties, its direct anti-aging efficacy and the specific molecular pathways through which it operates remain largely unexplored. MethodsTo comprehensively evaluate the anti-aging properties of dimethylglycine, we utilized replicative senescent human embryonic lung fibroblasts, specifically the WI-38 cell line, as an experimental model in a controlled laboratory environment. Cell viability and safety were thoroughly assessed using Cell Counting Kit-8 and lactate dehydrogenase release assays across various concentrations of dimethylglycine. The impact of dimethylglycine on cellular senescence phenotypes, oxidative stress, and proliferative capacity was evaluated via senescence-associated beta-galactosidase staining, reactive oxygen species fluorescence detection, and 5-ethynyl-2'-deoxyuridine incorporation assays. Furthermore, the molecular alterations of senescence-associated secretory phenotype factors and core senescence signaling pathways were quantified using quantitative reverse transcription polymerase chain reaction for the messenger RNA levels of interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1, and enzyme-linked immunosorbent assay for the measurement of p16 and p21 protein expression levels. For the living organism model, the wild-type nematode Caenorhabditis elegans was used to evaluate systemic physiological effects. We conducted a comprehensive lifespan analysis at 20°C, heat stress resistance survival assays at 35℃, senescence-associated beta-galactosidase staining, lipofuscin accumulation tracking, intracellular reactive oxygen species measurement, and Oil Red O staining to ascertain systemic lipid accumulation. Additionally, network pharmacology bioinformatics tools, including PharmMapper and STRING databases, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were utilized to predict target pathways, alongside highly detailed molecular docking simulations utilizing SwissDock and Protein-Ligand Interaction Profiler to examine interactions with the cytochrome P450 family 2 subfamily C member 9 protein. ResultsThe experimental outcomes robustly demonstrate the potent anti-aging capabilities of dimethylglycine. At the cellular level, toxicity analyses firmly confirmed that dimethylglycine is highly safe; continuous treatment with 50 mol/L and 70 mol/L of dimethylglycine for 5 d did not induce any cellular membrane damage or cytotoxicity, but rather actively promoted cellular proliferation. Utilizing the optimal standardized concentration of 50 mol/L, dimethylglycine treatment significantly ameliorated senescent phenotypic markers in human embryonic lung fibroblasts, which was evidenced by a drastic and highly significant reduction in the senescence-associated beta-galactosidase positive cell percentage (P<0.000 1) and intracellular reactive oxygen species levels (P<0.000 1), alongside a marked increase in the 5-ethynyl-2'-deoxyuridine-positive proliferation rate (P=0.003 5). On a molecular expression scale, dimethylglycine significantly downregulated the messenger RNA expression of multiple core senescence-associated secretory phenotype inflammatory factors, including interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1. Concurrently, it effectively suppressed the protein expression of critical cell cycle arrest markers, diminishing p16 protein levels by 57.3% (P=0.000 4) and p21 protein levels by 27.2% (P=0.000 7). In the nematode Caenorhabditis elegans animal model, dimethylglycine significantly extended the mean lifespan from 20.402 d to an impressive 23.066 d (P<0.000 1) and notably enhanced overall survival rates under severe heat stress environmental conditions (P=0.017). Furthermore, systemic dimethylglycine intervention significantly mitigated age-related physiological decline by decreasing bodily lipofuscin accumulation (P<0.000 1), significantly reducing senescence-associated beta-galactosidase activity, lowering systemic reactive oxygen species fluorescence (P=0.008), and effectively alleviating overall fat accumulation (P<0.000 1). Mechanistically, extensive network pharmacology and Kyoto Encyclopedia of Genes and Genomes analyses strongly revealed that the potential targets of dimethylglycine are significantly enriched in fundamental drug metabolism and oxidative stress response pathways. Precision molecular docking simulations conclusively demonstrated that dimethylglycine forms highly stable structural interactions with the cytochrome P450 family 2 subfamily C member 9 protein, specifically highlighting the definitive formation of 5 stable hydrogen bonds involving serine 365, leucine 366, and serine 429 residues, as well as two critical salt bridge formations with arginine 97 and histidine 368 residues. It is additionally predicted to interact favorably with glutathione S-transferase family proteins. ConclusionDimethylglycine exhibits a profoundly significant and multifaceted anti-aging activity at both the cellular and entire living animal levels. By powerfully alleviating oxidative stress, heavily suppressing the core p16 and p21-dependent cellular senescence signaling pathways, and substantially mitigating the detrimental senescence-associated secretory phenotype, dimethylglycine effectively delays fundamental cellular senescence processes and drastically extends whole-organism lifespan. The biological mechanisms driving these robust protective effects are highly likely closely associated with its direct stable interactions with crucial metabolic and detoxifying enzyme systems, such as cytochrome P450 family 2 subfamily C member 9 and glutathione S-transferase family proteins, thereby systemically improving metabolic dysregulation and restoring critical redox homeostasis. This comprehensive study provides highly solid experimental evidence supporting dimethylglycine as a highly potent and safe potential anti-aging intervention agent, while simultaneously offering a clear molecular mechanistic explanation for the previously documented high abundance of dimethylglycine observed within exceptionally long-lived human populations.

Rheumatoid arthritis （RA） is a common autoimmune disease characterised clinically by symmetrical joint pain， swelling， and stiffness. Long-term chronic synovial inflammation can lead to severe joint damage and even disability， thereby affecting quality of life for patients. Current clinical treatment of RA emphasises an integrated approach combining traditional Chinese and Western medicine， with traditional Chinese medicine offering certain advantages in reducing disease activity of RA， preventing relapses， and other aspects. Modern clinical evidence confirms that Guizhi Shaoyao Zhimutang （GSZT） is effective in improving symptoms such as immune metabolism， joint stiffness， and joint pain in RA patients. Pharmacological studies have revealed that GSZT primarily contains components such as cinnamaldehyde， total glucosides of paeony， total alkaloids of Aconiti Lateralis Radix Praeparata， glycyrrhetinic acid， zingiberone， isoimperatorin， ephedra polysaccharides， and cedrol. It improves RA symptoms via multiple mechanisms and targets， including enhancing immune responses， exerting anti-inflammatory and analgesic effects， regulating relevant signalling pathways， inhibiting cell apoptosis， and suppressing bone destruction. This paper reviewed the syndrome patterns and pharmacological basis of GSZT in the treatment of RA， as well as its clinical applications and related mechanisms， thereby providing a theoretical basis and reference for the further development and utilisation of GSZT in the treatment of RA.

Rheumatoid arthritis （RA） is a common autoimmune disease characterised clinically by symmetrical joint pain， swelling， and stiffness. Long-term chronic synovial inflammation can lead to severe joint damage and even disability， thereby affecting quality of life for patients. Current clinical treatment of RA emphasises an integrated approach combining traditional Chinese and Western medicine， with traditional Chinese medicine offering certain advantages in reducing disease activity of RA， preventing relapses， and other aspects. Modern clinical evidence confirms that Guizhi Shaoyao Zhimutang （GSZT） is effective in improving symptoms such as immune metabolism， joint stiffness， and joint pain in RA patients. Pharmacological studies have revealed that GSZT primarily contains components such as cinnamaldehyde， total glucosides of paeony， total alkaloids of Aconiti Lateralis Radix Praeparata， glycyrrhetinic acid， zingiberone， isoimperatorin， ephedra polysaccharides， and cedrol. It improves RA symptoms via multiple mechanisms and targets， including enhancing immune responses， exerting anti-inflammatory and analgesic effects， regulating relevant signalling pathways， inhibiting cell apoptosis， and suppressing bone destruction. This paper reviewed the syndrome patterns and pharmacological basis of GSZT in the treatment of RA， as well as its clinical applications and related mechanisms， thereby providing a theoretical basis and reference for the further development and utilisation of GSZT in the treatment of RA.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Objective: Scutellarin in Shuganning injection has potential allergenicity and is prone to causing anaphylactoid reactions. There is an urgent need to establish a simple and rapid chromatographic quantitative method to achieve the limit control of scutellarin in Shuganning injection.
Methods: For scutellarin, HPLC method was used in the quantitative analysis using a Shim-pack GIS C₁₈ (2.1 mm×150 mm, 5 μm) column. The mobile phase was a blend of 0.1% trifluoroacetic acid in water and acetonitrile, and gradient elution progress was applied for the whole process. The flow rate was 0.3 mL·min^-1 and the column temperature was maintained at 37 ℃. The detecting wavelength was 320 nm.
Results: The linear regression equation was y=51 456x-27 352, the correlation coefficient r=0.999 8, namely the calibration curve was linear in the range of 1.02-102.00 μg·mL^-1; the average recovery was 103.76%; the detection and quantification limit for determining scutellarin was 0.16 μg·mL^-1 and 0.57 μg·mL^-1, respectively; the injection sample was stable at room temperature for 48 h.
Conclusion: This method is easy to operate, reproducible and has high accuracy, thus can be used for quality control of Shuganning injection.

Osteoblasts primarily originate from mesenchymal stem cells (MSCs) within the bone marrow. These stem cells possess the ability to differentiate into osteoblasts, which are responsible for secreting bone matrix, promoting bone formation, and contributing to bone remodeling. Dysfunction in osteoblast activity can lead to various bone-related disorders, such as osteoporosis, delayed fracture healing, and skeletal deformities. In recent years, due to the adverse effects associated with the use of parathyroid hormone (PTH) analogs, bisphosphonates, and calmodulin-targeting drugs, there has been growing interest in exploring the mechanisms underlying osteoblast differentiation. Researchers are increasingly focusing on identifying natural compounds as potential treatments for osteoporosis. Among the signaling pathways involved, the Wnt/β-catenin pathway is recognized as a key regulator of osteoblast differentiation and a crucial therapeutic target in osteoporosis. However, both upregulation and downregulation of this pathway have been implicated in various diseases, including cancers. This review highlights the role of the Wnt/β-catenin signaling pathway in osteoblast differentiation, examines the association between pathway-related proteins and human diseases, and summarizes recent advancements in the development of natural compounds targeting this pathway for osteoporosis therapy.

Objective: To define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

ObjectiveTo perform metabolic associated fatty liver disease （MAFLD） screening among individuals attending community health institutions， to identify the patients at a low， moderate or high risk of advanced liver fibrosis based on fibrosis-4 index （FIB-4） and liver stiffness measurement （LSM） measured by liver transient elastography， and to implement stratified management. MethodsA cross-sectional study was conducted among 630 individuals attending Beijing Baizhifang Community Health Service Center from January to July 2024， and they were divided into MAFLD group and non-MAFLD group. According to body mass index （BMI）， the MAFLD group was further divided into lean MAFLD group （BMI<23 kg/m²） and non-lean MAFLD group （BMI≥23 kg/m²）. The above groups were compared in terms of demographic features， laboratory markers， hepatic steatosis， and LSM. Fibrosis risk stratification was performed for MAFLD patients based on FIB-4 and LSM， and a closed-loop management system involving referral to tertiary hospitals and follow-up at community health institutions was implemented. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsThere were 445 individuals （70.6%） in the MAFLD group and 185 individuals （29.4%） in the non-MAFLD group. Compared with the non-MAFLD group， the MAFLD group had a significantly lower proportion of male individuals （χ²=4.299， P<0.05）， a significant reduction in the level of high-density lipoprotein cholesterol （Z=3.484， P<0.05）， and significant increases in body weight （Z=-7.366， P<0.05）， BMI （Z=-9.740， P<0.05）， waist circumference （Z=-6.397， P<0.05）， hip circumference （Z=-6.935， P<0.05）， alanine aminotransferase （ALT） （Z=-2.765， P<0.05）， fasting blood glucose （Z=-3.646， P<0.05）， triglyceride （TG） （Z=-6.569， P<0.05）， total cholesterol （Z=-2.033， P<0.05）， low-density lipoprotein cholesterol （Z=-2.935， P<0.05）， controlled attenuation parameter （CAP） （Z=-19.784， P<0.05）， and LSM （Z=-5.703， P<0.05）. Within the MAFLD group， there were 124 individuals （27.9%） in the lean MAFLD group and 321 individuals （72.1%） in the non-lean MAFLD group. Compared with the non-lean MAFLD group， the lean MAFLD group had significantly lower body weight （Z=-12.414， P<0.05）， BMI （Z=-16.363， P<0.05）， waist circumference （Z=-7.733， P<0.05）， hip circumference （Z=-8.595， P<0.05）， ALT （Z=-2.835， P<0.05）， aspartate aminotransferase （Z=-1.972， P<0.05）， TG （Z=-2.407， P<0.05）， CAP （Z=-4.429， P<0.05）， degree of steatosis （χ²=16.588， P<0.05）， and LSM （Z=-3.908， P<0.05）. Based on the results of FIB-4 and LSM， 76 patients at a moderate or high risk of liver fibrosis should be referred to a higher-level hospital for further management. ConclusionThe detection rate of MAFLD reaches 70.6% among the individuals attending community health institutions， among whom 76 （17.1%） should be referred to a higher-level hospital. Establishing a liver fibrosis risk stratification and management system based on FIB-4 and LSM among MAFLD individuals in communities provides a practical pathway for chronic disease management and referral system construction in community health institutions.

The classic formula Fangji Fulingtang is from ZHANG Zhongjing's Synopsis of the Golden Chamber in the Eastern Han dynasty. It is composed of Stephaniae Tetrandrae Radix， Astragali Radix， Cinnamomi Ramulus， Poria， and Glycyrrhizae Radix et Rhizoma， with the effects of reinforcing Qi and invigorating spleen， warming Yang and promoting urination. By a review of ancient medical books， this paper summarizes the composition， original plants， processing， dosage， decocting methods， indications and other key information of Fangji Fulingtang， aiming to provide a literature basis for the research， development， and clinical application of preparations based on this formula. Synonyms of Fangji Fulingtang exist in ancient medical books， while the formula composition in the Synopsis of the Golden Chamber is more widespread and far-reaching. In this formula， Stephaniae Tetrandrae Radix， Astragali Radix， Cinnamomi Ramulus， Poria， and Glycyrrhizae Radix et Rhizoma are the dried root of Stephania tetrandra， the dried root of Astragalus embranaceus var. mongholicus， the dried shoot of Cinnamomum cassia， the dried sclerotium of Poria cocos， and the dried root and rhizome of Glycyrrhiza uralensis， respectively. Fangji Fulingtang is mainly produced into powder， with the dosage and decocting method used in the past dynasties basically following the original formula. Each bag is composed of Stephaniae Tetrandrae Radix 13.80 g， Astragali Radix 13.80 g， Cinnamomi Ramulus 13.80 g， Poria 27.60 g， and Glycyrrhizae Radix et Rhizoma 9.20 g. The raw materials are purified， decocted in water from 1 200 mL to 400 mL， and the decoction should be taken warm， 3 times a day. Fangji Fulingtang was originally designed for treating skin edema， and then it was used to treat impediment in the Qing dynasty. In modern times， it is mostly used to treat musculoskeletal and connective tissue diseases and circulatory system diseases， demonstrating definite effects on various types of edema and heart failure. This paper clarifies the inheritance of Fangji Fulingtang and reveals its key information （attached to the end of this paper）， aiming to provide a theoretical basis for the development of preparations based on this formula.