1.The prediction of clinical severity grading of catecholaminergic polymorphic ventricular tachycardia by RyR2 gene mutation: A systematic review
Ruyuan HE ; Jingxuan ZHANG ; Song DING ; Qing GENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(01):141-149
Objective To explore the genetic mutation characteristics, clinical manifestations, and treatment outcomes of catecholaminergic polymorphic ventricular tachycardia (CPVT), and to construct a quantitative scoring system for the severity of CPVT. The correlation between the mutations in different structural domains of the RyR2 gene and clinical manifestations and prognosis was analyzed. Methods By searching the PubMed and Web of Science databases for CPVT-related case reports published up to December 2024, data such as patient age, clinical manifestations, gene mutation sites, and treatment responses were collected. The quality of the literature was assessed using the CARE guidelines. The χ2 test was used to compare the severity and treatment response differences among different RyR2 structural domain mutation groups, and an innovative quantitative scoring system based on symptoms and efficacy was established. Results A total of 80 articles were included, with 102 patients in total. The quality of the literature was reliable. The age of the patients ranged from 1 to 84 years, with a higher proportion of children under 10 years old (25.5%). Female patients (54.9%) outnumbered males (45.1%). For CPVT patients, a quantitative scoring system was developed, with a total score of 2 to 10 points. Among them, 2 to 4 points were classified as mild, 5 to 7 points as moderate, and 8 to 10 points as severe. The results showed that severe patients often had a history of cardiac arrest and were resistant to treatment. Out of the 102 CPVT patients, RyR2 gene mutations accounted for 53.9% (55/102) of patients. Among them, the proportion of severe patients with N-terminal structural domain mutations was significantly higher than other regions, indicating that the RyR2 gene mutation structural domain has a significant impact on the severity of CPVT (χ2=17.530, P=0.008). The proportion of patients with mutations in the central hinge region who were ineffective with β-blockers reached 42.9% (3/7), which was significantly higher than other regions. Left cardiac sympathectomy was performed in 24 cases, and postoperative symptoms were almost completely controlled, significantly better than the drug treatment group.Conclusion Mutations in the N-terminal structural domain of the RyR2 gene are significantly correlated with the severity of CPVT. Left cardiac sympathectomy has gradually become an effective intervention for refractory cases. The scoring system proposed in this study can provide a basis for clinical stratified treatment. In the future, there is a need to expand the sample size to verify mutation-specific treatment strategies.
2.Research progress on the mechanisms and prevention of saphenous vein graft failure after coronary artery bypass grafting
Liaoming HE ; Tiemuerniyazi XIERAILI ; Yangwu SONG ; Wei FENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(03):475-483
The saphenous vein graft (SVG) remains the most commonly used conduit in coronary artery bypass grafting (CABG), yet its limited long-term patency adversely affects patient outcomes. SVG failure is a multistage pathological process, characterized by early thrombosis, intermediate intimal hyperplasia, and late atherosclerotic degeneration. These changes are driven by endothelial dysfunction induced by ischemia-reperfusion and mechanical injury, smooth muscle cell phenotypic modulation, inflammatory activation, and conventional cardiovascular risk factors. Preventive strategies for SVG failure have increasingly focused on both surgical and pharmacological optimization. Surgical approaches include appropriate target vessel and anastomotic site selection, refinement of SVG harvesting techniques (notably the no-touch technique and endoscopic vein harvesting), optimization of graft configurations, and routine intraoperative graft flow assessment. Postoperative secondary prevention is essential, as antithrombotic and lipid-lowering therapies have been shown to reduce SVG occlusion. In addition, emerging therapies, including gene-based interventions, antiproliferative agents, novel graft preservation solutions, and external vein graft supports, show promise in improving SVG durability. Integrated multimodal strategies may further reduce SVG failure and improve long-term outcomes after CABG. This article provides a review of researches related to SVG failure, including the mechanisms of failure, intraoperative preventive measures, pharmacological prevention, and recent advances in treatment, aiming to offer insights for clinical diagnosis, treatment and future studies.
3.Network meta-analysis of the efficacy and safety of dual amoxicillin-based regimens for Helicobacter pylori eradication
Ziwen SONG ; Xinmiao YUAN ; Liyuan LUO ; Yufang HE ; Lingshu YANG ; Yixu HUANG ; Jianpeng SHE ; Peihan WEI ; Sihan GUO ; Fei DUAN
China Pharmacy 2026;37(8):1074-1079
OBJECTIVE To evaluate the efficacy and safety of amoxicillin combined with proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) for Helicobacter pylori (Hp) eradication. METHODS Randomized controlled trial (RCTs) on amoxicillin combined with PPI or P-CAB for Hp eradication were retrieved from PubMed, Embase, the Cochrane Library, Web of Science, CNKI, Wanfang, and VIP data. The search time frame was from database inception to September 5, 2025. After literature screening, data extraction, and quality assessment, a network meta-analysis was performed using Stata 17.0 software. RESULTS A total of 12 RCTs involving 5 515 patients were included, encompassing 8 therapeutic regimens: PPI combined with high-dose amoxicillin for 14 days (TR1), PPI combined with low-dose amoxicillin for 14 days (TR2), P-CAB combined with high-dose amoxicillin for 7 days (TR3), P-CAB combined with high-dose amoxicillin for 14 days (TR4), P-CAB combined with high-dose amoxicillin for 10 days (TR5), P-CAB combined with low-dose amoxicillin for 7 days (TR6), P-CAB combined with low-dose amoxicillin for 14 days (TR7), and P-CAB combined with low-dose amoxicillin for 10 days (TR8). The network meta-analysis results showed that, in terms of intention-to-treat Hp eradication rates, the eradication rates of TR5 and TR4 were significantly higher than those of TR3, TR8, TR6 and TR1 ( P <0.05). The surface under the cumulative ranking curve (SUCRA) values from highest to lowest were: TR4 (89.7%)>TR5 (82.3%)>TR7 (71.5%)> TR2 (48.6%)>TR1 (43.9%)>TR8 (28.7%)>TR3 (22.7%)>TR6 (12.6%). Regarding safety, the incidence of adverse reactions in TR3 and TR5 was significantly lower than that in TR1 ( P <0.05). The SUCRA values from highest to lowest were: TR1 (91.3%)>TR4 (79.8%)>TR5 (55.0%)>TR7 (50.9%)>TR8 (41.3%)>TR2 (36.4%)>TR3 (27.6%) >TR6 (17.7%). CONCLUSIONS Although the regimen of P-CAB combined with high-dose amoxicillin for 14 days demonstrates the best efficacy, the combination of P-CAB with high-dose amoxicillin for 10 days exhibits a better balanced profile in terms of both efficacy and safety.
4.Therapeutic Effect and Mechanism of Solanum nigrum on Hepatic Fibrosis Induced by Carbon Tetrachloride in Rats
Min WU ; Zhenxiang AN ; Yuanli HE ; Weinong WEN ; Qiang SU ; Song HE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):117-125
ObjectiveTo investigate the therapeutic effect and mechanism of Solanum nigrum on hepatic fibrosis induced by carbon tetrachloride (CCl4) in rats. MethodsSixty SD rats were randomly allocated into blank, model, low-, medium-, and high-dose (0.9, 1.8, 3.6 g·kg-1, respectively) S. nigrum, and silibinin capsules (18.9 mg·kg-1) groups. Except the blank group, the other groups were subjected to intraperitoneal injection of 40% CCl4 solution for the modeling of hepatic fibrosis. After 4 weeks of gavage, blood was collected from the abdominal aorta following intraperitoneal anesthesia. The rats were sacrificed, and the liver was separated. The pathological changes were observed by hematoxylin-eosin staining and Masson staining. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver fibrosis indexes [type Ⅲ procollagen (PCⅢ), type Ⅳ collagen (Col Ⅳ), laminin (LN), and hyaluronic acid (HA)] in the rat serum were determined. The mRNA and protein levels of B cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein (Bax)/cysteinyl aspartate-specific proteinase-3 (Caspase-3) pathway-related factors were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. ResultsCompared with the blank group, the model group exhibited significant hepatocyte edema, infiltration of inflammatory cells, connective tissue proliferation, and collagen fiber deposition in the liver tissue. Compared with the model group, low-, medium-, and high-dose S. nigrum and silymarin capsules significantly improved the structure of liver cells and alleviated the edema, inflammatory cell infiltration, connective tissue proliferation, and collagen fiber deposition. Compared with those in the blank group, the serum levels of ALT, AST, PCⅢ, Col Ⅳ, LN, and HA were elevated in the model group (P<0.01). Compared with the model group, the serum levels of ALT, AST, PCⅢ, Col Ⅳ, LN, and HA were reduced in all the treatment groups (P<0.05). Real-time PCR and Western blot results showed that compared with the blank group, the model group had up-regulated mRNA and protein levels of Bcl-2 and down-regulated mRNA and protein levels of Bax and Caspase-3 (P<0.01). Compared with the model group, all the treatment groups showed down-regulated mRNA and protein levels of Bcl-2 and up-regulated mRNA and protein levels of Bax and Caspase-3 (P<0.05), with the high-dose S. nigrum group showing the best therapeutic effect. ConclusionS. nigrum modulates the progression of hepatic fibrosis in rats by regulating apoptosis through the Bcl-2/Bax/caspase-3 pathway.
5.Clinical Efficacy of Qi-regulating and Phlegm-removing Method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) in Treating AECOPD with Increased EOS
Renjie HUANG ; Wangqin YU ; Wuyinuo TANG ; Hong SONG ; Lyuyuan HE ; Wenbo LIN ; Guanyi WU ; Hang HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):149-156
ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) for treating acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with increased eosinophils (EOS). MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group (EG) or a control group (CG). Both groups received conventional Western medicine, with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2). The secondary efficacy indicators included the TCM symptom scores, the COPD Assessment Test (CAT) score, the Modified Medical Research Council (mMRC) Dyspnea Scale score, and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG, EG showed no significant difference in PaO2 (P=0.773), PaCO2 (P=0.632) and or CAT score (P=0.336) at on day 3 but better PaO2 (P=0.004), PaCO2 (P=0.008), and CAT score (P=0.013) were significantly better at on day 7. Compared with CGAfter treatment, EG had lower TCM syndrome scores of than CG EG on day 3 (P=0.005) and day 7 were significantly decreased (P0.001). There was no significant difference in mMRC score between the two groups on day 3 (P=0.514) and day 7 (P=0.176) as wasor the length of hospital stay (P=0.915). The generalized linear mixed model (GLMM) showed that compared with CG, EG had significant improvements over time in PaO2, PaCO2, TCM syndrome symptom scores, CAT score, and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.
6.Clinical Efficacy of Qi-regulating and Phlegm-removing Method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) in Treating AECOPD with Increased EOS
Renjie HUANG ; Wangqin YU ; Wuyinuo TANG ; Hong SONG ; Lyuyuan HE ; Wenbo LIN ; Guanyi WU ; Hang HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):149-156
ObjectiveTo assess the efficacy and safety of the Qi-regulating and phlegm-removing method(Liu Junzitang Combined with Linggang Wuwei Jiangxintang) for treating acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with increased eosinophils (EOS). MethodsSixty-eight AECOPD patients with increased EOS who were hospitalized in the Department of Pulmonary Diseases of Jinhua Traditional Chinese Medicine Hospital from April 2023 to April 2024 were recruited and randomly assigned to an experimental group (EG) or a control group (CG). Both groups received conventional Western medicine, with the EG additionally receiving Liujunzitang and Linggan Wuwei Jiangxintang. The therapeutic efficacy indicators were measured after the treatment. The main therapeutic efficacy indicators included partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2). The secondary efficacy indicators included the TCM symptom scores, the COPD Assessment Test (CAT) score, the Modified Medical Research Council (mMRC) Dyspnea Scale score, and the length of hospital stay. The indicators were measured at baseline and on days 3 and 7 of intervention. The safety was evaluated based on the adverse events. ResultsBaseline characteristics were not statistically different between the two groups. Compared with CG, EG showed no significant difference in PaO2 (P=0.773), PaCO2 (P=0.632) and or CAT score (P=0.336) at on day 3 but better PaO2 (P=0.004), PaCO2 (P=0.008), and CAT score (P=0.013) were significantly better at on day 7. Compared with CGAfter treatment, EG had lower TCM syndrome scores of than CG EG on day 3 (P=0.005) and day 7 were significantly decreased (P0.001). There was no significant difference in mMRC score between the two groups on day 3 (P=0.514) and day 7 (P=0.176) as wasor the length of hospital stay (P=0.915). The generalized linear mixed model (GLMM) showed that compared with CG, EG had significant improvements over time in PaO2, PaCO2, TCM syndrome symptom scores, CAT score, and mMRC score. ConclusionRegulating qi Qi and removing phlegm combined with conventional Western medicine can significantly alleviateimprove the clinical symptoms and improve the lung function of AECOPD patients with increased EOS increased AECOPDwhich has and demonstrates good safety.
7.DYRK2:a novel therapeutic target for rheumatoid arthritis combined with osteoporosis based on East Asian and European populations
Zhilin WU ; Qin HE ; Pingxi WANG ; Xian SHI ; Song YUAN ; Jun ZHANG ; Hao WANG
Chinese Journal of Tissue Engineering Research 2026;30(6):1569-1579
BACKGROUND:Studies have shown that rheumatoid arthritis and osteoporosis are positively correlated,but the causal relationship and related mechanisms have not yet been confirmed.With the cross-fertilization of computer science and life sciences,Mendelian randomization and bioinformatics analyses based on genome-wide association study(GWAS)and transcriptome sequencing data can assess the causal relationship between two diseases,explore the related mechanisms,and mine the therapeutic targets,which will be beneficial to the precision treatment of rheumatoid arthritis combined with osteoporosis.OBJECTIVE:To explore the causal relationship between rheumatoid arthritis and osteoporosis using two-sample Mendelian randomization and to mine potential co-morbid targets and potential targeted drugs through summary-data-based Mendelian randomization and bioinformatics analyses,aiming to provide theoretical basis for mechanism exploration and precision treatment in the field of rheumatoid arthritis combined with osteoporosis.METHODS:(1)Firstly,GWAS data of rheumatoid arthritis,osteoporosis,and cis-expression quantitative trait locus(cis-eQTL)in Asian and European populations were downloaded from the GWAS Catalog,IEU Open GWAS,FinnGen,and eQTLGen databases,and were used for two-sample Mendelian randomization analysis and summary-data-based Mendelian randomization analysis.(2)Transcriptome sequencing data of rheumatoid arthritis(GSE93272 and GSE15573)were downloaded from the GEO database for bioinformatics analysis.(3)Subsequently,forward and inverse Mendelian randomization analyses between rheumatoid arthritis and osteoporosis were performed,and inverse variance weighted was used as the main metric for the analyses,and the results were corroborated with MR Egger,simple mode,weighted median and weighted mode.(4)Then,the genes closely related to rheumatoid arthritis and osteoporosis were identified based on the summary-data-based Mendelian randomization analysis,and the co-disease targets of rheumatoid arthritis and osteoporosis were mined based on cross-analysis.Meanwhile,the biological functions of the co-morbid targets were verified based on bioinformatics analysis and cellular experiments.(5)In addition,a rheumatoid arthritis risk prediction nomogram was constructed based on DYRK2,and its prediction performance was verified by receiver operating characteristic curve,correction curve and decision curve.Finally,the target potential drugs were mined based on Enrichr database and molecular docking was performed.RESULTS AND CONCLUSION:(1)Forward Mendelian randomization analysis of rheumatoid arthritis and osteoporosis showed statistically significant results except for GCST90044540 and GCST90086118,and all other results indicated a significant causal relationship and positive correlation between rheumatoid arthritis and osteoporosis.(2)Inverse Mendelian randomization analysis suggested that no significant causal relationship was seen between osteoporosis and rheumatoid arthritis.(3)Summary-data-based Mendelian randomization analysis identified a total of 412 and 344 genes positively associated with rheumatoid arthritis and osteoporosis,and 421 and 347 genes negatively associated.Based on the cross-analysis,26 co-morbid genes were subsequently obtained.Among them,DYRK2 was a potential therapeutic target,and subsequent bioinformatics analysis and cellular experiments confirmed its important role in the progression of rheumatoid arthritis and osteoporosis.(4)Furthermore,the constructed nomogram has excellent predictive performance.Finally,four potential DYRK2-targeting drugs(undecanoic acid,metyrapone,JNJ-38877605,and ACA)were discovered and molecular docking also demonstrated reliable targeting ability.(5)In conclusion,based on GWAS data from Asian and European populations,we successfully demonstrated that rheumatoid arthritis and osteoporosis are causally related at the genetic level,DYRK2 is a potential therapeutic target,and four small molecules are potential target drugs.
8.DYRK2:a novel therapeutic target for rheumatoid arthritis combined with osteoporosis based on East Asian and European populations
Zhilin WU ; Qin HE ; Pingxi WANG ; Xian SHI ; Song YUAN ; Jun ZHANG ; Hao WANG
Chinese Journal of Tissue Engineering Research 2026;30(6):1569-1579
BACKGROUND:Studies have shown that rheumatoid arthritis and osteoporosis are positively correlated,but the causal relationship and related mechanisms have not yet been confirmed.With the cross-fertilization of computer science and life sciences,Mendelian randomization and bioinformatics analyses based on genome-wide association study(GWAS)and transcriptome sequencing data can assess the causal relationship between two diseases,explore the related mechanisms,and mine the therapeutic targets,which will be beneficial to the precision treatment of rheumatoid arthritis combined with osteoporosis.OBJECTIVE:To explore the causal relationship between rheumatoid arthritis and osteoporosis using two-sample Mendelian randomization and to mine potential co-morbid targets and potential targeted drugs through summary-data-based Mendelian randomization and bioinformatics analyses,aiming to provide theoretical basis for mechanism exploration and precision treatment in the field of rheumatoid arthritis combined with osteoporosis.METHODS:(1)Firstly,GWAS data of rheumatoid arthritis,osteoporosis,and cis-expression quantitative trait locus(cis-eQTL)in Asian and European populations were downloaded from the GWAS Catalog,IEU Open GWAS,FinnGen,and eQTLGen databases,and were used for two-sample Mendelian randomization analysis and summary-data-based Mendelian randomization analysis.(2)Transcriptome sequencing data of rheumatoid arthritis(GSE93272 and GSE15573)were downloaded from the GEO database for bioinformatics analysis.(3)Subsequently,forward and inverse Mendelian randomization analyses between rheumatoid arthritis and osteoporosis were performed,and inverse variance weighted was used as the main metric for the analyses,and the results were corroborated with MR Egger,simple mode,weighted median and weighted mode.(4)Then,the genes closely related to rheumatoid arthritis and osteoporosis were identified based on the summary-data-based Mendelian randomization analysis,and the co-disease targets of rheumatoid arthritis and osteoporosis were mined based on cross-analysis.Meanwhile,the biological functions of the co-morbid targets were verified based on bioinformatics analysis and cellular experiments.(5)In addition,a rheumatoid arthritis risk prediction nomogram was constructed based on DYRK2,and its prediction performance was verified by receiver operating characteristic curve,correction curve and decision curve.Finally,the target potential drugs were mined based on Enrichr database and molecular docking was performed.RESULTS AND CONCLUSION:(1)Forward Mendelian randomization analysis of rheumatoid arthritis and osteoporosis showed statistically significant results except for GCST90044540 and GCST90086118,and all other results indicated a significant causal relationship and positive correlation between rheumatoid arthritis and osteoporosis.(2)Inverse Mendelian randomization analysis suggested that no significant causal relationship was seen between osteoporosis and rheumatoid arthritis.(3)Summary-data-based Mendelian randomization analysis identified a total of 412 and 344 genes positively associated with rheumatoid arthritis and osteoporosis,and 421 and 347 genes negatively associated.Based on the cross-analysis,26 co-morbid genes were subsequently obtained.Among them,DYRK2 was a potential therapeutic target,and subsequent bioinformatics analysis and cellular experiments confirmed its important role in the progression of rheumatoid arthritis and osteoporosis.(4)Furthermore,the constructed nomogram has excellent predictive performance.Finally,four potential DYRK2-targeting drugs(undecanoic acid,metyrapone,JNJ-38877605,and ACA)were discovered and molecular docking also demonstrated reliable targeting ability.(5)In conclusion,based on GWAS data from Asian and European populations,we successfully demonstrated that rheumatoid arthritis and osteoporosis are causally related at the genetic level,DYRK2 is a potential therapeutic target,and four small molecules are potential target drugs.
9.Yougui Yin attenuates adipogenic differentiation of bone marrow mesenchymal stem cells by modulating PPARγ pathway to treat glucocorticoid-induced osteonecrosis.
Hong-Zhong XI ; Hao CHEN ; Shuai HE ; Wei SONG ; Jia-Hao FU ; Bin DU ; Xin LIU
China Journal of Chinese Materia Medica 2025;50(12):3356-3367
This study aims to investigate the pharmacological effects and mechanisms of Yougui Yin in treating glucocorticoid-induced osteonecrosis. A rat model of glucocorticoid-associated osteonecrosis of the femoral head(GA-ONFH) was established by intramuscular injection of dexamethasone at 20 mg·kg~(-1) every other day for 8 weeks. Rats were randomly allocated into control, model, and low-and high-dose(1.5 and 3.0 g·kg~(-1), respectively) Yougui Yin groups. After modeling, rats in Yougui Yin groups were administrated with Yougui Yin via gavage, which was followed by femoral specimen collection. Hematoxylin-eosin staining was employed to observe femoral head repair, and immunofluorescence was employed to assess adipogenic differentiation of bone marrow mesenchymal stem cells(BMSCs) within the femoral head. Cell experiments were carried out with dexamethasone(1 μmol·L~(-1))-treated BMSCs to evaluate the effects of Yougui Yin-medicated serum on adipogenic differentiation. Animal experiments demonstrated that compared with the model group, Yougui Yin at both high and low doses significantly improved bone mineral density(BMD), bone volume/total volume(BV/TV) ratio, and trabecular thickness(Tb.Th) in the femoral head. Additionally, Yougui Yin alleviated necrosis-like changes and adipocyte infiltration and significantly reduced the expression level of peroxisome proliferator-activated receptor γ(PPARγ) in the femoral head, thereby suppressing the adipogenic differentiation of BMSCs in GA-ONFH rats. The cell experiments revealed that Yougui Yin-medicated serum markedly inhibited dexamethasone-induced adipogenic differentiation of BMSCs and down-regulated the level of PPARγ. The overexpression of PPARγ attenuated the inhibitory effect of Yougui Yin-medicated serum on the adipogenic differentiation of BMSCs, indicating the critical role of PPARγ in Yougui Yin-mediated suppression of adipogenic differentiation of BMSCs. In conclusion, Yougui Yin exerts therapeutic effects on glucocorticoid-induced osteonecrosis by down-regulating PPARγ expression and inhibiting adipogenic differentiation of BMSCs.
Animals
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Mesenchymal Stem Cells/metabolism*
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PPAR gamma/genetics*
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Rats
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Drugs, Chinese Herbal/administration & dosage*
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Male
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Glucocorticoids/adverse effects*
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Rats, Sprague-Dawley
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Adipogenesis/drug effects*
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Osteonecrosis/genetics*
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Cell Differentiation/drug effects*
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Bone Marrow Cells/metabolism*
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Femur Head Necrosis/chemically induced*
;
Humans
10.Mechanism of Chaijin Jieyu Anshen Formula in regulating synaptic damage in nucleus accumbens neurons of rats with insomnia complicated with depression through TREM2/C1q axis.
Ying-Juan TANG ; Jia-Cheng DAI ; Song YANG ; Xiao-Shi YU ; Yao ZHANG ; Hai-Long SU ; Zhi-Yuan LIU ; Zi-Xuan XIANG ; Jun-Cheng LIU ; Hai-Xia HE ; Jian LIU ; Yuan-Shan HAN ; Yu-Hong WANG ; Man-Shu ZOU
China Journal of Chinese Materia Medica 2025;50(16):4538-4545
This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals
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Male
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Rats
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Nucleus Accumbens/metabolism*
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Drugs, Chinese Herbal/administration & dosage*
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Depression/complications*
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Membrane Glycoproteins/genetics*
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Rats, Sprague-Dawley
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Sleep Initiation and Maintenance Disorders/complications*
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Neurons/metabolism*
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Receptors, Immunologic/genetics*
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Signal Transduction/drug effects*
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Synapses/metabolism*

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