ObjectiveBased on the clinical characteristics of chronic gouty arthritis （CGA） in both traditional Chinese and western medicine， this study aims to systematically evaluate the clinical concordance of existing CGA animal models， providing recommendations for establishing animal models that align with the pathological characteristics of CGA and the manifestations of traditional Chinese medicine syndromes. MethodsBy comprehensively retrieving Chinese and international databases such as China National Knowledge Infrastructure， Wanfang， VIP Chinese Science and Technology Periodical Database （VIP）， and PubMed， all relevant literature on CGA animal models was collected. Based on the guidelines， the diagnostic criteria of both traditional Chinese and western medicine were summarized and organized. The evaluation indicators for the CGA model were constructed with reference to existing evaluation modes， and the CGA animal models were analyzed to systematically evaluate the clinical concordance of existing models. ResultsThe current methods used to construct CGA animal models mainly include monosodium urate crystal induction， high-protein diet induction （poultry lack urate oxidase）， and high-fat diet combined with urate oxidase inhibitors and joint injection. Based on 11 pieces of included literature， the traditional Chinese and western medicine scoring data of each model were extracted， and the average scoring values of all models were ultimately calculated. The results show that the average clinical concordances of existing CGA animal models in both traditional Chinese and western medicine are 43.33% and 64.44%， respectively. Among them， the model with the highest clinical concordance rate is the one with a high-fat diet combined with potassium oxonate to induce hyperuricemia plus joint injection， achieving 83.33% clinical concordance in western medicine and 60% in traditional Chinese medicine. This model aligns well with the pathogenic characteristics and pathological changes of clinical CGA. ConclusionAlthough current CGA animal models can simulate some pathological characteristics of CGA， they struggle to comprehensively reflect the complex pathological processes of CGA and the characteristics of traditional Chinese medicine syndromes. Therefore， in the future， it is necessary to establish the CGA animal models that incorporate the clinical disease and syndrome characteristics of traditional Chinese and western medicine and formulate the uniform model evaluation criteria， providing more precise tools for CGA mechanism research and the development of traditional Chinese medicine.

Objective: To evaluate the intervention effect of school based salt reduction health education, so as to provide a scientific basis for constructing a more effective and sustainable salt reduction intervention model for children. Methods: According to a randomized controlled trial design, in June 2022, probability proportional to size sampling was used to select 501 second grade students (248 in the control group and 253 in the intervention group) from 10 primary schools in Zhenjiang (intervention group) and 10 primary schools in Yangzhou (control group), Jiangsu Province. An one year school based salt reduction health education intervention was implemented. This included 20 online and 8 offline health education sessions, monitoring of salt consumption in the canteen, and the establishment of a salt reduction environment on campus. The control group received no additional salt reduction interventions. A questionnaire survey and 24 hour urinary sodium test were conducted before and after the intervention. The difference in differences method was used to evaluate the intervention effect. Results: After the intervention, the intervention group showed significant net intervention effects in knowledge aspects, including knowing that primary school students consume less salt than adults ( OR=3.55,95%CI =1.69-7.47), daily salt intake of primary school students ( OR=6.64,95%CI =3.71-11.87), long term high salt intake leading to hypertension ( OR=6.83,95%CI =3.93-11.91), low salt intake not causing hair graying ( OR= 1.66 ,95%CI =1.00-2.75), salt content in food labels ( OR=4.56,95%CI =2.63-7.91), and common high salt foods ( OR=3.39,95%CI =1.87-6.14) (all P <0.05). In terms of attitude, the net intervention effect for having a positive attitude toward using less salt in home cooking was significantly increased ( OR=1.88,95%CI =1.13-3.12, P <0.05). There were no statistically significant net intervention effects for salt reduction related behaviors (all P >0.05). There was no statistically significant difference in the changes of 24 hour urinary sodium between the intervention group and the control group before and after intervention ( P >0.05). Conclusions School based salt reduction health education effectively improves students salt reduction knowledge and attitudes but has a limited effect on behavior change. The home-school collaboration should be strengthened, and the dietary environment should be optimized simultaneously.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

ObjectiveTo improve the therapeutic effect of Buyang Huanwutang（BYHW） on diabetic kidney disease （DKD） and explore new methods for developing new Chinese medicine decoctions，we utilized 5-hydroxymethylcytosine （5hmC）-Seal sequencing technology and network pharmacology to modify BYHW. MethodsWe selected 14 diabetes mellitus （DM） patients and 15 DKD patients hospitalized in the Department of Endocrinology of Peking University Third Hospital in 2021. Circulating free DNA （cfDNA） in the patients’ plasma was sequenced. After data processing and screening， we performed temporal clustering analysis to select a DKD 5hmC gene set， which was then cross-validated with a DKD database gene set to obtain the DKD gene set. We retrieved target genes of the seven herbal components of BYHW from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）， and performed cross-analysis with the DKD gene set to identify common genes shared by the disease and the Chinese medicines. A protein-protein interaction （PPI） network was constructed for the common genes to screen out the key genes. Chinese medicines targeting these key genes were searched against ETCM to identify removable Chinese medicines. Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed on non-common DKD genes， and key genes in DKD-related pathways were selected based on machine learning. The GSE30529 dataset was used to verify the expression trends of 5hmC-modified genes and the feasibility of target genes as drug targets. TCMBank was used to search for target genes and obtain compounds targeting these genes and the corresponding Chinese medicines to construct a "key target-compound-Chinese medicine" network. Molecular docking was employed to verify the binding affinity of compounds with key targets. TCMSP and ETCM were used to search and count the candidate Chinese medicines targeting DKD-related genes， and a new decoction was formed by adding the selected Chinese medicines. A mouse model of DKD was established to examine the efficacy of the new decoction based on the mouse body mass， random blood glucose， urinary microalbumin （mALB）， serum creatinine （Scr）， and blood urea nitrogen （BUN） and by hematoxylin-eosin staining， periodic acid-Schiff staining， Masson staining， immunofluorescence assay， and Real-time PCR. ResultsThe cross-analysis results showed that the DKD gene set included 507 genes， of which 30 were target genes of BYHW. The PPI analysis indicated that the top 15% target genes regarding the degree were interleukin-6 （IL-6）， Toll-like receptor 4 （TLR4）， lactotransferrin （LTF）， lipoprotein lipase （LPL）， and sterol regulatory element-binding transcription factor 1 （SREBF1）. Persicae Semen and Pheretima in BYHW were unrelated to key genes and removed. Machine learning identified 10 potential target genes， among which TBC1 domain family member 5 （TBC1D5）， RAD51 paralog B （RAD51B）， and proteasome 20S subunit alpha 6 （PSMA6） had expression trends consistent with the GSE30529 dataset and could serve as drug targets. The "key target-compound-Chinese medicine" network and molecular docking results indicated that the compounds with good binding affinity to target proteins were arginine， glycine， myristicin， serine， and tyrosine， corresponding to 121 Chinese medicines. The top 10 Chinese medicines targeting DKD-related genes were Lycii Fructus， Ginseng Radix et Rhizoma， Dioscoreae Rhizoma， Rehmanniae Radix Praeparata， Isatidis Radix， Glehniae Radix， Ophiopogonis Radix， Allii Sativi Bulbus， Isatidis Folium， and Bolbostemmatis Rhizoma. Based on traditional Chinese medicine theory， the new decoction was obtained after removal of Persicae Semen and Pheretima and addition of Rehmanniae Radix Praeparata and Dioscoreae Rhizoma. Animal experiment results indicated that the modified BYHW improved the kidney function and inhibited renal fibrosis in DKD mice， with better effects than the original decoction. ConclusionThe BYHW modified based on 5hmC-Seal sequencing demonstrates better performance in inhibiting fibrosis and ameliorating DKD than the original decoction. This elucidates the biomedical theory behind the epigenetic modification of traditional Chinese medicine prescriptions， potentially offering new perspectives for the exploration of these prescriptions

ObjectiveTo improve the therapeutic effect of Buyang Huanwutang（BYHW） on diabetic kidney disease （DKD） and explore new methods for developing new Chinese medicine decoctions，we utilized 5-hydroxymethylcytosine （5hmC）-Seal sequencing technology and network pharmacology to modify BYHW. MethodsWe selected 14 diabetes mellitus （DM） patients and 15 DKD patients hospitalized in the Department of Endocrinology of Peking University Third Hospital in 2021. Circulating free DNA （cfDNA） in the patients’ plasma was sequenced. After data processing and screening， we performed temporal clustering analysis to select a DKD 5hmC gene set， which was then cross-validated with a DKD database gene set to obtain the DKD gene set. We retrieved target genes of the seven herbal components of BYHW from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）， and performed cross-analysis with the DKD gene set to identify common genes shared by the disease and the Chinese medicines. A protein-protein interaction （PPI） network was constructed for the common genes to screen out the key genes. Chinese medicines targeting these key genes were searched against ETCM to identify removable Chinese medicines. Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed on non-common DKD genes， and key genes in DKD-related pathways were selected based on machine learning. The GSE30529 dataset was used to verify the expression trends of 5hmC-modified genes and the feasibility of target genes as drug targets. TCMBank was used to search for target genes and obtain compounds targeting these genes and the corresponding Chinese medicines to construct a "key target-compound-Chinese medicine" network. Molecular docking was employed to verify the binding affinity of compounds with key targets. TCMSP and ETCM were used to search and count the candidate Chinese medicines targeting DKD-related genes， and a new decoction was formed by adding the selected Chinese medicines. A mouse model of DKD was established to examine the efficacy of the new decoction based on the mouse body mass， random blood glucose， urinary microalbumin （mALB）， serum creatinine （Scr）， and blood urea nitrogen （BUN） and by hematoxylin-eosin staining， periodic acid-Schiff staining， Masson staining， immunofluorescence assay， and Real-time PCR. ResultsThe cross-analysis results showed that the DKD gene set included 507 genes， of which 30 were target genes of BYHW. The PPI analysis indicated that the top 15% target genes regarding the degree were interleukin-6 （IL-6）， Toll-like receptor 4 （TLR4）， lactotransferrin （LTF）， lipoprotein lipase （LPL）， and sterol regulatory element-binding transcription factor 1 （SREBF1）. Persicae Semen and Pheretima in BYHW were unrelated to key genes and removed. Machine learning identified 10 potential target genes， among which TBC1 domain family member 5 （TBC1D5）， RAD51 paralog B （RAD51B）， and proteasome 20S subunit alpha 6 （PSMA6） had expression trends consistent with the GSE30529 dataset and could serve as drug targets. The "key target-compound-Chinese medicine" network and molecular docking results indicated that the compounds with good binding affinity to target proteins were arginine， glycine， myristicin， serine， and tyrosine， corresponding to 121 Chinese medicines. The top 10 Chinese medicines targeting DKD-related genes were Lycii Fructus， Ginseng Radix et Rhizoma， Dioscoreae Rhizoma， Rehmanniae Radix Praeparata， Isatidis Radix， Glehniae Radix， Ophiopogonis Radix， Allii Sativi Bulbus， Isatidis Folium， and Bolbostemmatis Rhizoma. Based on traditional Chinese medicine theory， the new decoction was obtained after removal of Persicae Semen and Pheretima and addition of Rehmanniae Radix Praeparata and Dioscoreae Rhizoma. Animal experiment results indicated that the modified BYHW improved the kidney function and inhibited renal fibrosis in DKD mice， with better effects than the original decoction. ConclusionThe BYHW modified based on 5hmC-Seal sequencing demonstrates better performance in inhibiting fibrosis and ameliorating DKD than the original decoction. This elucidates the biomedical theory behind the epigenetic modification of traditional Chinese medicine prescriptions， potentially offering new perspectives for the exploration of these prescriptions

Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

AIM To explore the clinical effects of Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation on patients with mild to moderate bronchial asthma in chronic and persistent period.METHODS One hundred and eighteen patients were randomly assigned into control group(59 cases)for 4-week administration of Budesonide and Formoterol Fumarate Powder for Inhalation,and observation group(59 cases)for 4-week administration of both Jiawei Yanghe Decoction and Budesonide and Formoterol Fumarate Powder for Inhalation.The changes in clinical effects,ACT score,bronchial asthma control rate,pulmonary function indices(FEV1,PEF,FEV1％,PEF％),inflammatory indices(EOS,EOS％,FeNO),TCM syndrome score and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed increased bronchial asthma control rate,ACT score,PEF(P＜0.05),and decreased TCM syndrome score(P＜0.05),especially for the observation group(P＜0.05);the observation group exhibited increased FEV1,FEV1％,PEF％(P＜0.05),among which FEV1,PEF％were higher than those in the control group(P＜0.05);the observation group showed decreased inflammatory indices(P＜0.05),among which FeNO was lower than that in the control group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with mild to moderate bronchial asthma in chronic and persistent period,Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation can safely and effectively alleviate clinical symptoms,improve pulmonary functions,airway inflammatory reactions,and enhance bronchial asthma control rate.

AIM To investigate the effects of Modified Baitouweng Decoction and Lizhong Decoction on mouse ulcerative colitis(UC).METHODS The mouse model of UC was established by 3％dextran sulfate sodium(DSS)induction.The C57BL/6 mice were randomly divided into the blank group,the model group,the low,medium and high dose Modified Baitouweng Decoction and Lizhong Decoction groups(3,6,12 g/kg),and sulfasalazine group(300 mg/kg),for 7 days gavage of the appropriate drugs,with 10 mice in each group.The mice had their disease activity index(DAI)and colonic mucosal damage index(CMDI)calculated;their colonic length and unit colonic weight measured;their histopathologic changes of colon observed by HE;their colonic ROS,MDA levels and GSH-Px,SOD activities detected by superoxide anion fluorescent probes and kits;their colonic levels of TNF-α,IL-6 and IL-1β detected by ELISA;their colonic LC3 expression detected by immunofluorescence method;and their colonic AMPK,mTOR and p70S6K protein expressions detected by Western blot method.RESULTS Compared with the blank group,the model group displayed significantly higher DAI score,CMDI score,unit colon weight,pathology score,ROS and MDA content,TNF-α,IL-6,and IL-1β levels,and mTOR and p70S6K protein expression(P＜0.01);and significantly lower colon length,GSH-Px and SOD activity,LC3 level,and phosphorylated AMPK protein expression(P＜0.01).Compared with the model group,the groups intervened with Modified Baitouweng Decoction and Lizhong Decoction or sulfasalazine shared decreased DAI score,CMDI score,unit colon mass,pathology score,ROS,MDA,TNF-α,IL-6,IL-1β levels,mTOR,p70S6K protein expressions(P＜0.01);and significantly improved symptomsin terms of the elevated colonic length,GSH-Px,SOD activities,LC3 level,AMPK protein expression(P＜0.01).CONCLUSION Modified Baitouweng Decoction and Lizhong Decoction may attenuate inflammatory response and oxidative damage in UC mouse models via AMPK/mTOR/p70S6K signaling pathway.