ObjectiveTo observe the pharmacodynamic efficacy of phlorizin in improving hepatic glycolipid metabolism disorders in type 2 diabetic mellitus （T2DM） rats and to explore its mechanism of action based on the insulin receptor substrate-1 （IRS-1）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsA high-fat diet and streptozotocin （STZ） were used to establish T2DM rat models. The rats were randomly assigned into six groups： the blank control group， model group， metformin group （300 mg·kg^-1）， and phlorizin high-dose （100 mg·kg^-1） and low-dose groups （25 mg·kg^-1）. The rats were given intragastric administration for 6 weeks. The changes in body weight and fasting blood glucose （FBG） were observed， and the oral glucose tolerance test （OGTT） was carried out. The levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， glycated serum protein （GSP）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in serum were detected by an automatic biochemical analyzer. The levels of fasting insulin （FINS）， interleukin （IL）-1β， IL-6， and tumour necrosis factor （TNF）-α were detected by enzyme-linked immunosorbent assay （ELISA）. The levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were detected by the biochemical assays. The pancreas index， liver index， and insulin resistance index were calculated. Hematoxylin-eosin （HE） staining was used to evaluate the pathological changes in liver and pancreatic tissues. The immunofluorescence method was used to detect the changes in insulin and glucagon in pancreatic tissue. Western blot was used to detect the expression of related proteins in the IRS-1/PI3K/Akt pathway of liver tissue and its downstream glycogen synthase kinase-3β （GSK-3β） and forkhead box transcription factor O1 （FoxO1） proteins. ResultsCompared with the blank control group， the body weight of rats in the model group continued to decrease， while the FBG level increased significantly. The area under the OGTT blood glucose curve （AUC）， GSP， TC， TG， LDL-C， IL-1β， IL-6， TNF-α， MDA， pancreatic index and liver index increased significantly， while the levels of HDL-C， SOD， and FINS decreased significantly （P0.05， P0.01）. Histological results showed that the pancreatic islets of rats in the model group exhibited atrophy and severe structural abnormalities. The insulin-positive β-cells decreased significantly （P0.01）， while the glucagon-positive α-cells increased significantly （P0.01）. Inflammatory cell infiltration and partial necrosis were observed in the liver tissues of the model group rats. The expressions of p-IRS-1/IRS-1， p-GSK-3β/GSK-3β， and p-FoxO1/FoxO1 proteins in the liver of the model group increased significantly （P0.01）， while the expressions of p-PI3K/PI3K and p-Akt/Akt proteins decreased significantly （P0.01）. Compared with the model group， the diabetic symptoms of rats in all administration groups were improved. The changes in body weight and FBG were close to those of the blank control group. The levels of OGTT-AUC， GSP， TC， TG， LDL-C， MDA， IL-1β， IL-6， TNF-α and the pancreatic index， liver index were obviously reduced （P0.05， P0.01）， while the levels of HDL-C， SOD， and FINS obviously increased （P0.05， P0.01）. The pathological changes of the pancreas and liver in rats in all treatment groups were effectively improved. The insulin-positive β-cells in the pancreas increased significantly （P0.01）， while the glucagon-positive α-cells decreased significantly （P0.01）. The protein expressions of p-IRS-1/IRS-1， p-GSK-3β/GSK-3β， and p-FoxO1/FoxO1 in the liver were significantly reduced （P0.01）， while the protein expressions of p-PI3K/PI3K and p-Akt/Akt significantly increased （P0.01）. ConclusionPhlorizin reversed the weight loss and abnormal increase of FBG in T2DM rats， improved blood lipid profiles， oxidative stress， and inflammatory levels， alleviated insulin resistance， and had certain protective effects on the liver and pancreas. The hypoglycemic mechanism may involve regulating the IRS-1/PI3K/Akt signaling pathway to inhibit the activities of GSK-3β and FoxO1， thereby promoting liver glycogen synthesis and suppressing hepatic gluconeogenesis， ultimately improving glycolipid metabolism disorders.

ObjectiveTo observe the pharmacodynamic efficacy of phlorizin in improving hepatic glycolipid metabolism disorders in type 2 diabetic mellitus （T2DM） rats and to explore its mechanism of action based on the insulin receptor substrate-1 （IRS-1）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsA high-fat diet and streptozotocin （STZ） were used to establish T2DM rat models. The rats were randomly assigned into six groups： the blank control group， model group， metformin group （300 mg·kg^-1）， and phlorizin high-dose （100 mg·kg^-1） and low-dose groups （25 mg·kg^-1）. The rats were given intragastric administration for 6 weeks. The changes in body weight and fasting blood glucose （FBG） were observed， and the oral glucose tolerance test （OGTT） was carried out. The levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， glycated serum protein （GSP）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in serum were detected by an automatic biochemical analyzer. The levels of fasting insulin （FINS）， interleukin （IL）-1β， IL-6， and tumour necrosis factor （TNF）-α were detected by enzyme-linked immunosorbent assay （ELISA）. The levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were detected by the biochemical assays. The pancreas index， liver index， and insulin resistance index were calculated. Hematoxylin-eosin （HE） staining was used to evaluate the pathological changes in liver and pancreatic tissues. The immunofluorescence method was used to detect the changes in insulin and glucagon in pancreatic tissue. Western blot was used to detect the expression of related proteins in the IRS-1/PI3K/Akt pathway of liver tissue and its downstream glycogen synthase kinase-3β （GSK-3β） and forkhead box transcription factor O1 （FoxO1） proteins. ResultsCompared with the blank control group， the body weight of rats in the model group continued to decrease， while the FBG level increased significantly. The area under the OGTT blood glucose curve （AUC）， GSP， TC， TG， LDL-C， IL-1β， IL-6， TNF-α， MDA， pancreatic index and liver index increased significantly， while the levels of HDL-C， SOD， and FINS decreased significantly （P0.05， P0.01）. Histological results showed that the pancreatic islets of rats in the model group exhibited atrophy and severe structural abnormalities. The insulin-positive β-cells decreased significantly （P0.01）， while the glucagon-positive α-cells increased significantly （P0.01）. Inflammatory cell infiltration and partial necrosis were observed in the liver tissues of the model group rats. The expressions of p-IRS-1/IRS-1， p-GSK-3β/GSK-3β， and p-FoxO1/FoxO1 proteins in the liver of the model group increased significantly （P0.01）， while the expressions of p-PI3K/PI3K and p-Akt/Akt proteins decreased significantly （P0.01）. Compared with the model group， the diabetic symptoms of rats in all administration groups were improved. The changes in body weight and FBG were close to those of the blank control group. The levels of OGTT-AUC， GSP， TC， TG， LDL-C， MDA， IL-1β， IL-6， TNF-α and the pancreatic index， liver index were obviously reduced （P0.05， P0.01）， while the levels of HDL-C， SOD， and FINS obviously increased （P0.05， P0.01）. The pathological changes of the pancreas and liver in rats in all treatment groups were effectively improved. The insulin-positive β-cells in the pancreas increased significantly （P0.01）， while the glucagon-positive α-cells decreased significantly （P0.01）. The protein expressions of p-IRS-1/IRS-1， p-GSK-3β/GSK-3β， and p-FoxO1/FoxO1 in the liver were significantly reduced （P0.01）， while the protein expressions of p-PI3K/PI3K and p-Akt/Akt significantly increased （P0.01）. ConclusionPhlorizin reversed the weight loss and abnormal increase of FBG in T2DM rats， improved blood lipid profiles， oxidative stress， and inflammatory levels， alleviated insulin resistance， and had certain protective effects on the liver and pancreas. The hypoglycemic mechanism may involve regulating the IRS-1/PI3K/Akt signaling pathway to inhibit the activities of GSK-3β and FoxO1， thereby promoting liver glycogen synthesis and suppressing hepatic gluconeogenesis， ultimately improving glycolipid metabolism disorders.

Guided by the theory of "the kidney storing essence, governing the bones, and producing marrow", this study explored the mechanism of icariin(ICA) in regulating the osteogenic differentiation of rat bone mesenchymal stem cells(BMSCs) through caveolin-1(Cav1) via in vitro and in vivo experiments, aiming to provide a theoretical basis for the prevention and treatment of postmenopausal osteoporosis with traditional Chinese medicine(TCM). Primary cells were obtained from 4-week-old female SD rats using the whole bone marrow adherent method. Flow cytometry was used to detect the expression of surface markers CD29, CD90, CD11b, and CD45. The potential for osteogenic and adipogenic differentiation was assessed. The effect of ICA on cell viability was determined using the CCK-8 assay, and the impact of ICA on the formation of mineralized nodules was verified by alizarin red staining. A stable Cav1-silenced cell line was constructed using lentivirus. The effect of Cav1 silencing on osteogenic differentiation was observed via alizarin red staining. Western blot analysis was conducted to detect the expression of Cav1, Hippo/TAZ, and osteogenic markers such as Runt-related transcription factor 2(RUNX2) and alkaline phosphatase(ALP). The results showed that primary cells were successfully obtained using the whole bone marrow adherent method, positively expressing surface markers of rat BMSCs and possessing the potential for both osteogenic and adipogenic differentiation. The CCK-8 assay and alizarin red staining results indicated that 1×10~(-7) mol·L~(-1) was the optimal concentration of ICA for intervention in this experiment(P<0.05). During osteogenic induction, ICA inhibited Cav1 expression(P<0.05) while promoting TAZ expression(P<0.05). Alizarin red staining demonstrated that Cav1 silencing significantly promoted the osteogenic differentiation of BMSCs. After ICA intervention, TAZ expression was activated, and the expression of osteogenic markers ALP and RUNX2 was increased. In conclusion, Cav1 silencing significantly promotes the osteogenic differentiation of BMSCs, and ICA promotes this differentiation by inhibiting Cav1 and regulating the Hippo/TAZ signaling pathway.
Animals ; Mesenchymal Stem Cells/metabolism* ; Caveolin 1/genetics* ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; Cell Differentiation/drug effects* ; Female ; Signal Transduction/drug effects* ; Flavonoids/administration & dosage* ; Protein Serine-Threonine Kinases/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Cells, Cultured ; Humans

This study investigates the effect and underlying mechanism of Guizhi Tongluo Tablets(GZTL) in treating atherosclerosis(AS) in a mouse model. Apolipoprotein E-knockout(ApoE~(-/-)) mice were randomly assigned to the following groups: model, high-, medium-, and low-dose GZTL, and atorvastatin(ATV), and age-matched C57BL/6J mice were selected as the control group. ApoE~(-/-) mice in other groups except the control group were fed with a high-fat diet for the modeling of AS and administrated with corresponding drugs via gavage for 8 weeks. General conditions, signs of blood stasis, and body mass of mice were monitored. Aortic plaques and their stability were assessed by hematoxylin-eosin, Masson, and oil red O staining. Serum levels of total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) were measured by biochemical assays, and those of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) were determined via enzyme-linked immunosorbent assay. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL). Single-cell RNA sequencing(scRNA-seq) was employed to analyze the differential expression of CD72hi macrophages(CD72hi-Mφ) in the aortas of AS patients and mice. The immunofluorescence assay was employed to visualize CD72hi-Mφ expression in mouse aortic plaques, and real-time fluorescence quantitative PCR was utilized to determine the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. The results demonstrated that compared with the control group, the model group exhibited significant increases in body mass, aortic plaque area proportion, necrotic core area proportion, and lipid deposition, a notable decrease in collagen fiber content, and an increase in apoptosis. Additionally, the model group showcased elevated serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6, alongside marked upregulations in the mRNA levels of IL-1β, TNF-α, and IL-6 in the aorta. In comparison with the model group, the GZTL groups and the ATV group showed a reduction in body mass, and the medium-and high-dose GZTL groups and the ATV group demonstrated reductions in aortic plaque area proportion, necrotic core area proportion, and lipid deposition, an increase in collagen fiber content, and a decrease in apoptosis. Furthermore, the treatment goups showcased lowered serum levels of TC, TG, LDL-C, IL-1β, TNF-α, and IL-6. The data of scRNA-seq revealed significantly elevated CD72hi-Mφ signaling in carotid plaques of AS patients compared with that in the normal arterial tissue. Animal experiments confirmed that CD72hi-Mφ expression, along with several pro-inflammatory cytokines, was significantly upregulated in the aortas of AS mice, which were downregulated by GZTL treatment. In conclusion, GZTL may alleviate AS by inhibiting CD72hi-Mφ activity.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Atherosclerosis/immunology* ; Mice ; Mice, Inbred C57BL ; Macrophages/immunology* ; Male ; Humans ; Apolipoproteins E/genetics* ; Tablets ; Tumor Necrosis Factor-alpha/genetics* ; Apoptosis/drug effects* ; Interleukin-1beta/genetics* ; Interleukin-6/genetics* ; Disease Models, Animal ; Mice, Knockout

Quality control is a key link in the modernization process of traditional Chinese medicine(TCM). Studies have shown that the effects of active components in TCM depend on not only their chemical composition but also their suitable physical forms and states. The physical phase structures, such as micelles, vesicles, gels, and nanoparticles, can improve the solubility, delivery efficiency, and targeting precision of active components. These structures significantly enhance the pharmacological activity while reducing the toxicity and side effects, demonstrating functional activity surpassing that of active components and highlighting the key effects of "structures" on "functions" of active components. Taking the physical phase structure as a breakthrough point, this paper outlines the common types of TCM physical phase structures. Furthermore, this paper explores how to realize the quality upgrading of TCM through the precise regulation of physical phase structures based on the current applications and potential of TCM physical phase structures in processing to increase the efficacy and reduce the toxicity, compounding and decocting processes, drug delivery systems, and quality control, aiming to provide novel insights for the future quality control of TCM.
Quality Control ; Drugs, Chinese Herbal/standards* ; Medicine, Chinese Traditional/standards* ; Humans ; Drug Delivery Systems

This study aims to investigate the therapeutic effects of the Coptidis Rhizoma-Scutellariae Radix on cytokine storm secondary lung injury(CSSLI) induced by CpG1826 in mice, and to elucidate the potential molecular mechanisms by which its major active components, i.e., coptisine and wogonin, alleviate CSSLI by inhibiting the mitochondrial permeability transition pore(mPTP)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) inflammasome pyroptosis pathway. In vivo, a mouse model of CSSLI was established by CpG1826 induction. Pulmonary edema was assessed by lung wet-to-dry weight ratio(W/D), lung injury was evaluated by hematoxylin-eosin(HE) staining, and ultrastructural changes in lung tissue were observed by transmission electron microscopy(TEM). The levels of interleukin(IL)-1β, high mobility group box 1 protein(HMGB1), IL-18, and IL-1α in bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay(ELISA). The results showed that the decoction of the Coptidis Rhizoma-Scutellariae Radix significantly reduced pulmonary edema, alleviated lung injury, and decreased the concentrations of related cytokines in BALF more effectively than either single herb alone, thereby improving CSSLI. In vitro, a CpG1826-induced CSSLI model was established in mouse alveolar macrophage MH-S cells. Calcein-AM quenching was used to screen for the most effective monomer components from the herb pair in inhibiting mPTP opening. Coptisine(5, 10, 20 μmol·L~(-1)) and wogonin(10, 20, 40 μmol·L~(-1)) markedly inhibited mPTP opening, with optimal effects and a clear dose-dependent pattern. These components suppressed mPTP opening, thereby reducing the release of mitochondrial DNA(mtDNA) and the accumulation of reactive oxygen species(ROS), effectively reversing the CpG1826-induced decrease in mitochondrial membrane potential(MMP). Further studies revealed that both coptisine and wogonin inhibited pyroptosis and downregulated the expression of key proteins in the NLRP3/Caspase-1/gasdermin D(GSDMD) pathway. In conclusion, the Coptidis Rhizoma-Scutellariae Radix improves CpG1826-induced CSSLI in mice, and this effect is associated with the inhibition of the mPTP/NLRP3 pyroptosis pathway, providing scientific evidence for its clinical application and further development.
Animals ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Pyroptosis/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Male ; Lung Injury/immunology* ; Cytokines/immunology* ; Scutellaria baicalensis/chemistry* ; Oligodeoxyribonucleotides/adverse effects* ; Mice, Inbred C57BL ; Coptis chinensis

OBJECTIVE: Meta-analysis of the clinical efficacy of plate and external fixator fixation in the treatment of AO-C type distal radius fractures. METHODS: PubMed, Embase, Cochrane Medical Library, Web of Science, CNKI, Wanfang, VIP and SinoMed databases were searched for all literature on randomized controlled clinical trials of AO-C distal radius fractures. The search time limits were from each database. The database will be established until June 30, 2023. The included studies were extracted according to the Cochrane Handbook (Version 6.3, 2022) for information extraction and literature quality evaluation. RevMan 5.4 was used to evaluate the risk of Publication bias, test heterogeneity and Perform Meta-analysis. The outcome indicators were:imaging anatomy indicators (volar inclination angle, ulnar deviation angle, radial height), wrist joint mobility (flexion, extension, rotation, ulnar deviation), complication rate, and comparison of surgical treatments (operative blood loss, operation time, hospitalization time, fracture healing time) and wrist joint function scores and related scales. RESULTS: (1) A total of 28 studies were included, with a total of 2 192 patients, including 1 096 cases in the plate internal fixation group and 1 096 cases in the external fixation group.(2) Meta analysis results showed:the surgical treatment situation of the external fixation group:surgical blood loss MD=-37.93, 95%CI(-48.54, -27.31), P<0.000 01;operation time MD=-31.58, 95%CI(-48.96, -14.20), P<0.000 4;hospitalization time MD=-4.58, 95%CI(-5.44, -3.71), P<0.000 01;the fracture healing time MD=-0.88, 95%CI(-1.35, -0.41), P<0.000 2, which were significantly better than that of the plate internal fixation group(P<0.05).(3) The two groups:palmar inclination angle MD=-0.17, 95%CI(-0.95, 0.61), P=0.68;ulnar declination MD=0.22, 95%CI(-0.73, 1.17), P=0.65, radial height MD=-0.24, 95%CI(-1.15, 0.67), P=0.60;flexion and extension MD=-5.63, 95%CI(-11.85, 0.58), P=0.08;rotation MD=-5.80, 95%CI(-12.77, 1.17), P=0.10, radioulnar deviation MD=-2.86, 95%CI(-10.87, 5.15), P=0.48;complication rate RR=0.96, 95%CI(0.63, 1.46), P=0.83;Gartland-Werley clinical wrist score MD=0.13, 95%CI(-0.80, 1.06), P=0.78;excellent and good rate of Gartland-Werley wrist clinical score RR=0.93, 95%CI(0.87, 1.01), P=0.08;excellent and good rate of Cooney wrist score RR=0.99, 95%CI(0.62, 1.59), P=0.98;wrist DASH score MD=-4.67, 95%CI(-14.96, 5.62), P=0.37;the differences were not significant (P>0.05). CONCLUSION Compared with internal fixation with plate, external fixation can significantly reduce the amount of surgical bleeding, shorten the operation time, hospitalization time and fracture healing time, and its imaging anatomical indicators, wrist mobility, and complications can be significantly reduced in treating AO-C distal radius fractures. Rates and wrist function scores were equivalent.
Humans ; External Fixators ; Bone Plates ; Radius Fractures/surgery* ; Fracture Fixation/methods* ; Fracture Fixation, Internal ; Wrist Fractures

OBJECTIVE: This cross-sectional study assessed the methodological quality of systematic reviews (SRs) of Chinese herbal medicine (CHM) published in Chinese between Jan 2021 and Sep 2022. METHODS: Chinese language CHM SRs were identified through literature searches across 3 international and 4 Chinese databases. Methodological quality was appraised using A MeaSurement Tool to Assess systematic Reviews 2. Logistic regressions were used to explore associations between bibliographical characteristics and quality. RESULTS: Analyses of methodological quality found that among the 213 sampled SRs, 69.5% were of critically low quality, 30.5% were of low quality, and none achieved high or moderate quality. Common shortcomings included the failure to identify the studies excluded from the analysis, failure to disclose funding sources, and limited evaluation of the potential impact of bias on conclusions. Logistic regressions revealed that SRs led by corresponding authors affiliated with universities or academic institutions tended to be of lower quality than SRs led by authors affiliated with hospitals or clinical facilities. CONCLUSION Recent Chinese language CHM SRs exhibited limited methodological quality, making them unlikely to support the development of clinical practice guidelines. Urgent initiatives are needed to enhance training for researchers, peer-reviewers and editors involved in the preparation and publication of SRs. Adoption of Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines in Chinese language journals is crucial to improve the relevance of SRs for Chinese medicine development. Addressing deficiencies in methodology and reporting is essential for promoting evidence-based practices and informed clinical decisions in Chinese medicine. Please cite this article as: Jiang Y, Zhong CC, Wang BH, Xu SS, Ho FF, Kwong MH, Ho L, Zhou JHS, Lam KC, Liu JP, Zhang BT, Chung VCH. Methodological quality of systematic reviews on orally administered Chinese herbal medicine published in Chinese between 2021 and 2022: A cross-sectional study. J Integr Med. 2025; 23(5):492-501.
Cross-Sectional Studies ; Drugs, Chinese Herbal/administration & dosage* ; Systematic Reviews as Topic/standards* ; Humans ; China ; Administration, Oral ; Medicine, Chinese Traditional

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult