1.Predictive study of serum 25-hydroxyvitamin D and blood lipid metabolism indexes in occurrence of osteoporosis in type 2 diabetes mellitus
Jiajia SONG ; Xiaofang HAN ; Ting HU ; Xiaohuan ZHU
Journal of Public Health and Preventive Medicine 2026;37(1):154-157
Objective To explore the predictive effect of serum 25-hydroxyvitamin D3 [25(OH)D3] and blood lipid metabolism indexes on the occurrence of osteoporosis in type 2 diabetes mellitus (T2DM). Methods Totally 98 patients with T2DM in the hospital from January 2022 to January 2024 were classified into osteoporosis group (38 cases) and non-osteoporosis group (60 cases) by means of concurrent osteoporosis status. The levels of serum 25(OH)D3 and blood lipid metabolism indexes [high density lipoprotein (HDL), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), VLDL] were measured in study subjects. The association of serum 25(OH)D3 and blood lipid metabolism indexes with osteoporosis was explored by Logistic regression analysis. The predictive value of serum 25(OH)D3 and blood lipid metabolism indexes on osteoporosis was analyzed by receiver operating characteristic curve (ROC). Results Serum 25(OH)D3 and HDL levels in the osteoporosis group were lower while TG and LDL levels were higher than those in the non-osteoporosis group (P<0.05). The differences in the levels of TC and VLDL were insignificant between groups (P>0.05). After logistic regression analysis, the levels of serum 25(OH)D3, HDL, TG and LDL were closely related to the occurrence of osteoporosis (P<0.05). ROC curve indicated that the area under the curve (AUC), sensitivity and specificity of combined prediction of osteoporosis by serum 25(OH)D3, HDL, TG, and LDL were 0.943, 92.11% and 85.00%, and the efficiency of combined prediction was better than that of each index alone (P<0.05). Conclusion The levels of serum 25(OH)D3, HDL, TG and LDL in T2DM are closely related to osteoporosis. Early combined monitoring of the indicators can provide reference value for clinical prediction of osteoporosis occurrence in patients with T2DM.
2.Xuefu Zhuyutang Ameliorates Metabolic-associated Fatty Liver Disease via AMPK Signaling Pathway
Ming HAN ; Ying ZHANG ; Lingya KONG ; Jun DAI ; Ting ZHANG ; Zhihong MA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):1-12
ObjectiveTo investigate the therapeutic mechanism of Xuefu Zhuyutang (XFZYT) for metabolic-associated fatty liver disease (MAFLD) through integrated network pharmacology and animal experiments. MethodsNetwork pharmacology was utilized to predict the core components, key therapeutic targets, and signaling pathways of XFZYT in the treatment of MAFLD. For animal experiments, a rat model of MAFLD was established by feeding a high-cholesterol diet for 4 weeks. Intervention was then administered with low-dose (2 g·kg-1) and high-dose (4 g·kg-1) XFZYT for 2 weeks. Biochemical assays were performed to measure the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). In addition, the activities of superoxide dismutase (SOD) and catalase (CAT) and levels of malondialdehyde (MDA) and glutathione (GSH) in the serum were measured. The same way was adopted to measure the levels of TC and TG in the liver tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the serum levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-α). Histopathological evaluations included hematoxylin and eosin (HE) staining for liver tissue morphology, Oil Red O staining for lipid deposition, and dihydroethidium (DHE) probe staining for reactive oxygen species (ROS) levels. Western blot analysis was conducted to assess the protein levels of AMP-activated protein kinase (AMPK), phosphorylated (p)-AMPK, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB), and p-NF-κB in the liver tissue. Untargeted metabolomics analysis of the serum was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). ResultsNetwork pharmacology analysis predicted 155 potential targets of XFZYT for MAFLD treatment, with core targets including signal transducer and activator of transcription 3 (STAT3), protein kinase B1 (Akt1), TNF, and IL-6. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment primarily implicated the AMPK signaling pathway. Animal experiments demonstrated that compared with the normal group, the model group exhibited dyslipidemia, hepatic function impairment, pronounced hepatic lipid deposition, and inflammatory manifestations, with elevated serum levels of AST, ALT, TC, TG, LDL, and MDA (P<0.05), reduced HDL and GSH levels plus decreased SOD and CAT activities (P<0.05), downregulated protein levels of Nrf2, HO-1, and p-AMPK (P<0.05), and upregulated protein level of p-NF-κB (P<0.05) in the liver tissue. Compared with the model group, XFZYT intervention groups showed significant amelioration of dyslipidemia and hepatic function impairment, markedly reduced hepatic lipid deposition and inflammatory cell infiltration, decreased serum levels of AST, ALT, TC, TG, LDL, and MDA (P<0.05), increased HDL and GSH levels plus enhanced SOD and CAT activities (P<0.05), upregulated protein levels of Nrf2, HO-1, and p-AMPK (P<0.05), and downregulated protein level of p-NF-κB (P<0.05). Serum metabolomics revealed 511 differentially expressed metabolites (231 upregulated and 280 downregulated) between normal and model groups, while XFZYT groups versus model group showed 94 differential metabolites (51 upregulated and 43 downregulated). Among them, 11 metabolites displayed the most significant alterations, with enriched pathways including glycerolipid metabolism, cholesterol metabolism, and insulin resistance, multiple of which demonstrated AMPK association. ConclusionXFZYT alleviates MAFLD by regulating the AMPK signaling pathway and associated metabolic networks.
3.Traditional Chinese medicine syndrome and syndrome differentiation-based treatment of Wilson disease
Wenjie HAO ; Wenming YANG ; Ting CHENG ; Hailin JIANG ; Han WANG ; Meixia WANG
Journal of Clinical Hepatology 2026;42(3):522-528
Wilson disease (WD) is an autosomal recessive disorder of copper metabolism, and decoppering therapy and symptomatic treatment are the main Western medicine therapies for WD. This article systematically reviews the understanding of the etiology and pathogenesis of WD in traditional Chinese medicine (TCM) and points out that abnormal natural endowment is the core etiology and pathogenesis of WD, with internal accumulation of copper toxicity as the manifestation, liver/spleen/kidney dysfunction as the root cause, and intermingled “toxin, stasis, phlegm, and deficiency” as the key pathogenesis. Literature research and clinical observation are conducted to summarize the common TCM syndromes of WD, including stagnation of liver Qi, internal retention of damp-heat, phlegm-stasis-heat accumulation syndrome, liver-kidney Yin deficiency syndrome, spleen-kidney Yang deficiency, and syndrome of deficiency damage and phlegm stasis. This article proposes the corresponding therapies and representative prescriptions for each syndrome and discusses the advantages of treatment by stage and integrated traditional Chinese and Western medicine therapy. This article aims to provide a systematic reference for the syndrome differentiation-based treatment of WD in clinical practice of TCM, thereby giving full play to the advantages of TCM in the treatment of this disease.
4.Risk factors for rebleeding after endoscopic therapy for esophageal and gastric varices in liver cirrhosis patients and construction of a nomogram model
Huijuan SHAO ; Shini HAN ; Aiping ZHANG ; Yuling ZHANG ; Ting LI ; Ya HAN ; Jiucong ZHANG ; Wenshan DOU ; Xiuxia WANG ; Hongwei DU
Journal of Clinical Hepatology 2026;42(8):1845-1856
ObjectiveTo investigate the risk factors for rebleeding after endoscopic therapy for esophageal and gastric varices in liver cirrhosis patients, to construct a clinical predictive model, and to provide a reference for predicting rebleeding in the early stage, reducing the incidence rate of rebleeding, and improving the clinical outcome of patients. MethodsA retrospective analysis was performed for the clinical data of 194 liver cirrhosis patients with gastroesophageal variceal bleeding who received initial endoscopic therapy at Department of Gastroenterology, The Second People’s Hospital of Lanzhou, from January 1, 2021 to May 31, 2025. According to whether rebleeding occurred within 1 year after endoscopic therapy, the patients were divided into rebleeding group and non-rebleeding group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The patients enrolled were randomly divided into a training set and a validation set at a ratio of 7∶3. In the training set, the Lasso regression analysis was used to obtain optimal predictive variables, and the factors that might affect prognosis were included in the univariate and multivariate Logistic regression analyses to identify independent predictive factors for rebleeding after endoscopic therapy for esophageal and gastric varices in liver cirrhosis patients, which were used to construct a nomogram model. In both the training set and the validation set, the receiver operating characteristic (ROC) curve and the calibration curve were used to assess the discriminatory ability and calibration of the model, and decision curve analysis and the clinical impact curve were used to assess the clinical practicability of the model. ResultsAmong the 194 liver cirrhosis patients with esophageal and gastric varices, 116 (59.79%) experienced rebleeding within 1 year after endoscopic therapy, with 76 patients in the training set and 40 patients in the validation set. In the training set, the Lasso regression analysis and the univariate and multivariate Logistic regression analyses showed that etiology of liver cirrhosis (odds ratio [OR]=3.540, 95% confidence interval [CI]: 1.520 — 7.150, P<0.001), Child-Pugh class (OR=3.560, 95%CI: 1.380 — 9.500, P=0.019), severity of esophageal and gastric varices (OR=8.190, 95%CI: 3.568 — 17.850, P=0.026), and main portal vein diameter (OR=2.954, 95%CI: 1.349 — 15.030, P=0.044) were independent predictive factors for rebleeding of esophageal and gastric varices in liver cirrhosis patients. A nomogram model was constructed based on the above independent predictive factors. The ROC curve analysis showed that this model had an area under the ROC curve of 0.845 (95%CI: 0.778 — 0.912) in the training set and 0.801 (95%CI: 0.798 — 0.868) in the validation set. The model had an index of concordance of 0.832 in the training set and 0.820 in the validation set, suggesting that the model had a good discriminatory ability. The Hosmer-Lemeshow test showed P values of 0.320 and 0.550 in the training set and validation set, respectively, the calibration curve indicated that the predicted probabilities of the nomogram model were in good concordance with the actual observed probabilities, suggesting that the model had good calibration. The decision curve analysis and the clinical impact curve showed that the model had good clinical utility. ConclusionThe nomogram model based on etiology of liver cirrhosis, Child-Pugh class, severity of esophageal and gastric varices, and main portal vein diameter has a certain clinical value in predicting the risk of rebleeding from esophageal and gastric varices in liver cirrhosis.
5.A new tetralone glycoside in leaves of Cyclocarya paliurus.
Ting-Si GUO ; Qin HUANG ; Qi-Qi HU ; Fei-Bing HUANG ; Qing-Ling XIE ; Han-Wen YUAN ; Wei WANG ; Yu-Qing JIAN
China Journal of Chinese Materia Medica 2025;50(1):146-167
The chemical constituents from leaves of Cyclocarya paliurus were isolated and purified by chromatography on silica gel, C_(18) reverse-phase silica gel, and Sephadex LH-20 gel, as well as semi-preparative high-performance liquid chromatography. Six compounds were identified by UV, IR, NMR, MS, calculated ECD, and comparison with literature data as cyclopaloside D(1), boscialin(2),(5R,6S)-6-hydroxy-6-[(E)-3-hydroxybut-1-enyl]-1,1,5-trimethylcyclohexanone(3), 3S,5R-dihydroxy-6R,7-megastigmadien-9-one(4), 3S,5R-dihydroxy-6S,7-megastigmadien-9-one(5), and gingerglycolipid A(6), respectively. Among them, compound 1 was identified as a new tetralone glycoside, and compounds 2-6 were isolated from leaves of C. paliurus for the first time. Furthermore, compound 1 exhibited strong antioxidant activity, with the IC_(50) of(454.20±31.81)μmol·L~(-1) and(881.82±42.31)μmol·L~(-1) in scavenging DPPH and ABTS free radicals, respectively.
Plant Leaves/chemistry*
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Glycosides/isolation & purification*
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Juglandaceae/chemistry*
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Tetralones/isolation & purification*
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Drugs, Chinese Herbal/isolation & purification*
6.Research progress in chemical constituents and pharmacological activities of Abelmoschi Corolla and prediction of its quality markers.
Shi-Han GUAN ; Chang LIU ; Xiao-Tong YAN ; Jin-Wei HAN ; Feng-Ting YIN ; Hui SUN ; Guang-Li YAN ; Ling KONG ; Ying HAN ; Xi-Jun WANG
China Journal of Chinese Materia Medica 2025;50(4):908-921
Abelmoschi Corolla, the dried corolla of Abelmoschus manihot, has anti-inflammatory, antioxidant, and anti-fibrosis activities. Its chemical constituents mainly include flavonoids, organic acids, steroids, and polysaccharides. This study reviewed the research progress in the chemical constituents and pharmacological activities of Abelmoschi Corolla in recent 20 years. According to the concept of quality marker(Q-marker), the Q-markers of Abelmoschi Corolla were predicted from plant phylogeny, chemical constituent specificity, traditional efficacy, chemical constituent measurability, and absorbed constituents. The primary Q-markers for Abelmoschi Corolla were anticipated to include quercetin-3'-O-β-D-glucopyranoside, gossypetin-8-O-β-D-glucuronide, isoquercetin, myricetin,quercetin, and hyperoside, with the aim of providing reference data for improving the quality evaluation system of Abelmoschi Corolla.
Abelmoschus/chemistry*
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Drugs, Chinese Herbal/pharmacology*
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Flowers/chemistry*
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Humans
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Animals
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Quality Control
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Flavonoids/chemistry*
7.Buzhong Yiqi Decoction alleviates immune injury of autoimmune thyroiditis in NOD.H-2~(h4)mice via c GAS-STING signaling pathway.
Yi-Ran CHEN ; Lan-Ting WANG ; Qing-Yang LIU ; Zhao-Han ZHAI ; Shou-Xin JU ; Xue-Ying CHEN ; Zi-Yu LIU ; Xiao YANG ; Tian-Shu GAO ; Zhi-Min WANG
China Journal of Chinese Materia Medica 2025;50(7):1872-1880
This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals
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Drugs, Chinese Herbal/administration & dosage*
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Signal Transduction/drug effects*
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Thyroiditis, Autoimmune/metabolism*
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Mice
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Membrane Proteins/metabolism*
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Mice, Inbred NOD
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Humans
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Female
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Nucleotidyltransferases/metabolism*
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Male
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Disease Models, Animal
8.Mechanism of action of ginsenoside Rg_2 on diabetic retinopathy and angiogenesis based on YAP/TLRs pathway.
Zhuo-Rong LIU ; Yong-Li SONG ; Shang-Qiu NING ; Yue-Ying YUAN ; Yu-Ting ZHANG ; Gai-Mei HAO ; Jing HAN
China Journal of Chinese Materia Medica 2025;50(6):1659-1669
Ginsenoside Rg_2(GRg2) is a triterpenoid compound found in Panax notoginseng. This study explored its effects and mechanisms on diabetic retinopathy and angiogenesis. The study employed endothelial cell models induced by glucose or vascular endothelial growth factor(VEGF), the chorioallantoic membrane(CAM) model, the oxygen-induced retinopathy(OIR) mouse model, and the db/db mouse model to evaluate the therapeutic effects of GRg2 on diabetic retinopathy and angiogenesis. Transwell assays and endothelial tube formation experiments were conducted to assess cell migration and tube formation, while vascular area measurements were applied to detect angiogenesis. The impact of GRg2 on the retinal structure and function of db/db mice was evaluated through retinal thickness and electroretinogram(ERG) analyses. The study investigated the mechanisms of GRg2 by analyzing the activation of Yes-associated protein(YAP) and Toll-like receptors(TLRs) pathways. The results indicated that GRg2 significantly reduced cell migration numbers and tube formation lengths in vitro. In the CAM model, GRg2 exhibited a dose-dependent decrease in the vascular area ratio. In the OIR model, GRg2 notably decreased the avascular and neovascular areas, ameliorating retinal structural disarray. In the db/db mouse model, GRg2 increased the total retinal thickness and enhanced the amplitudes of the a-wave, b-wave, and oscillatory potentials(OPs) in the ERG, improving retinal structural disarray. Transcriptomic analysis revealed that the TLR signaling pathway was significantly down-regulated following YAP knockdown, with PCR results consistent with the transcriptome sequencing findings. Concurrently, GRg2 downregulated the expression of Toll-like receptor 4(TLR4), TNF receptor-associated factor 6(TRAF6), and nuclear factor-kappaB(NF-κB) proteins in high-glucose-induced endothelial cells. Collectively, GRg2 inhibits cell migration and tube formation and significantly reduces angiogenesis in CAM and OIR models, improving retinal structure and function in db/db mice, with its pharmacological mechanism likely involving the down-regulation of YAP expression.
Animals
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Ginsenosides/pharmacology*
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Diabetic Retinopathy/physiopathology*
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Mice
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YAP-Signaling Proteins
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Humans
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Male
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Signal Transduction/drug effects*
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Cell Movement/drug effects*
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Adaptor Proteins, Signal Transducing/genetics*
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Mice, Inbred C57BL
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Neovascularization, Pathologic/metabolism*
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Drugs, Chinese Herbal/administration & dosage*
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Panax notoginseng/chemistry*
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Endothelial Cells/metabolism*
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Transcription Factors/genetics*
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Angiogenesis
9.Expert consensus on evaluation index system construction for new traditional Chinese medicine(TCM) from TCM clinical practice in medical institutions.
Li LIU ; Lei ZHANG ; Wei-An YUAN ; Zhong-Qi YANG ; Jun-Hua ZHANG ; Bao-He WANG ; Si-Yuan HU ; Zu-Guang YE ; Ling HAN ; Yue-Hua ZHOU ; Zi-Feng YANG ; Rui GAO ; Ming YANG ; Ting WANG ; Jie-Lai XIA ; Shi-Shan YU ; Xiao-Hui FAN ; Hua HUA ; Jia HE ; Yin LU ; Zhong WANG ; Jin-Hui DOU ; Geng LI ; Yu DONG ; Hao YU ; Li-Ping QU ; Jian-Yuan TANG
China Journal of Chinese Materia Medica 2025;50(12):3474-3482
Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards*
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Humans
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Consensus
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Drugs, Chinese Herbal/therapeutic use*
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Surveys and Questionnaires
10.Mechanism of Yishen Jiangtang Decoction in regulating endoplasmic reticulum stress-mediated NLRP3 inflammasome to improve renal damage in diabetic nephropathy db/db mice.
Yun-Jie YANG ; Bin-Hua YE ; Chen QIU ; Han-Qing WU ; Bo-Wei HUANG ; Tong WANG ; Shi-Wei RUAN ; Fang GUO ; Jian-Ting WANG ; Ming-Qian JIANG
China Journal of Chinese Materia Medica 2025;50(10):2740-2749
This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.
Animals
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Endoplasmic Reticulum Stress/drug effects*
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Diabetic Nephropathies/metabolism*
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NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
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Drugs, Chinese Herbal/administration & dosage*
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Mice
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Inflammasomes/drug effects*
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Male
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Kidney/pathology*
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Endoplasmic Reticulum Chaperone BiP
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Humans
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Interleukin-18/genetics*
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Mice, Inbred C57BL


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