1.Molecular Mechanism of Danshen Tongluo Formula in Intervention of Coronary Artery Disease-dominated Panvascular Disease
Jiawen CHENG ; Chao LIU ; Jie WANG ; Yongmei LIU ; Wenjing LIAN ; Chengzhi HOU ; Chenyang ZHU ; Cheng MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):86-93
ObjectiveEndothelial cell dysfunction being the core link. This study explores the molecular mechanism of Danshen Tongluo formula in treating coronary artery disease-dominated panvascular disease with endothelial cell changes as the core through animal experiments and single-cell transcriptome sequencing. MethodsA rat model of coronary artery disease-dominated panvascular disease was established by ligating the left anterior coronary artery. Rats were randomized into a blank group, a model group, and a Danshen Tongluo formula (28 mg·kg-1·d-1) group. The efficacy was evaluated by examining the cardiac ultrasound, determination of the plasma level of N-terminal pro-brain natriuretic peptide, and pathological staining. After single-cell sequencing, SingleR package, public datasets, and related literature were used for annotation of the cells. Cell chat was used for intercellular communication and ligand-receptor analysis, and scmetabolism was used for metabolic analysis of endothelial cells. ResultsAnimal experiments showed that Danshen Tongluo formula reduced the N-terminal pro-brain natriuretic peptide ( NT-proBNP ) level (P<0.05), ameliorated myocardial cell damage and fibrosis, and increase left ventricular ejection fractions (LVEF) in the rat model of heart failure after myocardial infarction(P<0.05). Single-cell sequencing results showed that Danshen Tongluo formula increased the proportion of arterial endothelial cells, venous endothelial cells, and capillary-arterial endothelial cells, while reducing the proportion of capillary-venous endothelial cells. In addition, this formula increased the interaction intensity of endothelial cells with cardiomyocytes and M1 macrophages and reduced the interaction intensity of endothelial cells with fibroblasts and T cells. Danshen Tongluo formula upregulated CXCL12-CXCR4 signaling in endothelium-B cells and Ptprm-Ptprm signaling in endothelial endothelial cells, while downregulating Mif-(CD74+CXCR44) signaling in endothelium-M1 macrophages and Mif-(CD74+CD44) signaling in endothelium-M2 macrophages. It reduced the citric acid cycle, oxidative phosphorylation, and glycolysis and increased the glycolysis/oxidative phosphorylation ratio in endothelial cells. GO and KEGG enrichment analysis showed that arterial endothelial cells, venous endothelial cells, and venous capillary endothelial cells can all regulate oxidative phosphorylation, cell adhesion molecules, and tyrosine metabolism. Lymphatic endothelial cells regulate immunity and vascular constriction to participate in the metabolism of various amino acids and fatty acids. ConclusionDanshen Tongluo Formula can ameliorate coronary artery disease-dominated panvascular disease by changing the composition of endothelial cells and regulating the communication between myocardial endothelial cells and non-endothelial cells.
2.Celastrol directly targets LRP1 to inhibit fibroblast-macrophage crosstalk and ameliorates psoriasis progression.
Yuyu ZHU ; Lixin ZHAO ; Wei YAN ; Hongyue MA ; Wanjun ZHAO ; Jiao QU ; Wei ZHENG ; Chenyang ZHANG ; Haojie DU ; Meng YU ; Ning WAN ; Hui YE ; Yicheng XIE ; Bowen KE ; Qiang XU ; Haiyan SUN ; Yang SUN ; Zijun OUYANG
Acta Pharmaceutica Sinica B 2025;15(2):876-891
Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.
3.Effect of Tongfeng Decoction (痛风汤) on NLRP3 Inflammatory Vesicles and Neutrophil Extracellular Traps in Synovial Tissues of Ankle Joints in Acute Gouty Arthritis Model Rats
Yongzheng DENG ; Qingliang MENG ; Junfu MA ; Jiakang CUI ; Kai LI ; Gengfeng WANG ; Chenyang SONG ; Hua BIAN
Journal of Traditional Chinese Medicine 2024;65(17):1816-1824
ObjectiveTo explore the possible mechanism of Tongfeng Decoction (痛风汤) for preventing and treating acute gouty arthritis. MethodsSixty Wistar male rats were divided into normal group, model group, colchicine group and low-, medium- and high-dose Tongfeng Decoction groups according to the random number table, 10 rats in each group. Tongfeng Decoction of 11.34, 22.68 and 45.36 g/kg were given by gavage to low-, medium- and high-dose Tongfeng Decoction groups, colchicine 3.15×10-4 g/(kg·d) to the colchicine group, and normal saline 10 ml/(kg·d) to the normal group and model group respectively for 7 consecutive days. After 1 hour of gavage on day 5, rats in all groups except the normal group were modelled as acute gouty arthritis in the ankle joint of the right hind limb with the modified Coderre's method; rats in the normal group were injected with 0.2 ml of normal saline at the same location. The swelling degree of the ankle joint was measured before modelling and after 6 h, 12 h, 24 h and 48 h of modelling, respectively. HE staining was used to observe the histopathological and morphological changes in the synovial tissue of the ankle joint; immunoblotting and RT-qPCR were used to detect NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteine aspartate protease 1 (Caspase-1), and interleukin 1β (IL-1β) protein and mRNA expression levels in ankle synovial tissues, respectively; immunohistochemistry was used to detect the positive expression of Caspase-1 and IL-1β in ankle synovial tissues; ELISA was used to detect the tumour necrosis factor alpha (TNF-α), IL-1β, and interleukin in serum; immunofluorescence staining was used to observe the formation of neutrophil extracellular traps (NETs) in the synovial tissues of the ankle joints. ResultsCompared with the normal group, rats in the model group showed elevated joint swelling at all time points, significantly increased inflammatory cell infiltration and the number of synovial cell layers in the synovial tissues of the ankle joints, elevated NLRP3, Caspase-1, ASC and IL-1β protein and mRNA expression, elevated positive expression of Caspase-1 and IL-1β, increased formation of NETs, and elevation of TNF-α, IL-6, and IL-1β in serum (P<0.05). Compared with the model group, there was an improvement in synovial cell proliferation and inflammatory cell infiltration of the ankle joint in the colchicine group, high- and medium-dose Tongfeng Decoction groups. In the colchicine group and the high-, medium- and low-dose Tongfeng Decoction groups, the degree of joint swelling, positive expression of Caspase-1, IL-1β and formation of NETs in the synovial tissue of the ankle joint, and TNF-α, IL-6 and IL-1β in serum reduced 24 h and 48 h after modelling; in colchicine group and high-dose Tongfeng Decoction group, NLRP3, ASC, Caspase-1, IL-1β protein and mRNA expression in the synovial tissues of ankle joints all reduced (P<0.05). The colchicine group and high-dose Tongfeng Decoction group were superior to the low-dose Tongfeng Decoction group in reducing ASC, Caspase-1, IL-1β protein and mRNA expression in the ankle synovial tissues, the positive expression of Caspase-1, as well as TNF-α, IL-6, and IL-1β level in serum (P<0.05). ConclusionTongfeng Decoction showed effectiveness for the prevention and treatment of acute gouty arthritis, and its mechanism may be related to the inhibition of the assembly and activation of NLRP3 inflammatory vesicles in ankle synovial tissues, the inhibition of the release of inflammatory factors, and the formation of NETs.
4.Correlation between UGRP1 and apoptosis pathway mediated by Fas in hashimoto thyroiditis
Shanshan MA ; Yue WU ; Li ZHU ; Chenyang LU ; Chunlin ZUO
Acta Universitatis Medicinalis Anhui 2024;59(2):289-292
Objective To investigate the correlation between uterine globulin associated protein 1(UGRP1)and Fas mediated apoptosis pathway in hashimoto thyroiditis(HT).Methods The expression of UGRP1 in thyroid cells of normal people and HT patients was detected by immunohistochemistry(IHC).FRTL-5 cells were transfect-ed by plasmids in vitro,and control group,UGRP1 group,Fas group were established respectively.Real-time fluo-rescent quantitative reverse transcription PCR(RT-qPCR)was used to detect the expression of Fas and UGRP1 mRNA in each group.Results UGRP1 expression was positive in thyroid cells of HT patients and negative in that of normal people.There were no significant differences between control group and UGRP1 group in Fas gene ex-pression(1.085 0±0.124 9 vs 1.021 0±0.113 9).Compared with the control group,the expression of UGRP1 gene increased significantly in Fas group(P<0.000 1,5.807 0±0.323 2 vs 0.752 7±0.076 0).Conclusion The high expression of UGRP1 in HT may be related to apoptosis pathway mediated by Fas.
5.Research Status and Trend of Screening for Women's Common Diseases in China
Zixuan FAN ; Mengyao YAN ; Chenyang PEI ; Qianrun LEI ; Jing MA ; Yuanli LIU
Acta Academiae Medicinae Sinicae 2024;46(1):33-38
Objective To visualize the research status and hotspots of women's common disease screening based on CiteSpace 6.1.R6,and to provide a reference for the in-depth research in this field thereafter.Methods The relevant articles were retrieved from the China National Knowledge Infrastructure with the time in-terval from January 1,1992 to December 13,2022.The analysis was conducted on the number of annual publica-tions,countries(regions),institutions,author collaboration networks,keyword co-occurrence,clustering,and bursts.Results A total of 900 papers that met the criteria were included,and the number of annual publications showed a trend of first increasing and then decreasing.The cross-institutional collaboration network was mature.The re-search hotspots mainly covered women's health,the prevalence of women's diseases,reproductive health,and breast diseases.The hotspots have evolved from an initial focus on reproductive health care to gynecological disease management,and eventually to reproductive health and holistic health care in women.Conclusions The attention should be kept on the screening of women's common diseases.It is advisable to synchronize the screening of women's common diseases with the screening of cervical and breast cancers to expand the screening coverage,promote early disease detection and treatment,and comprehensively safeguard women's health.
6.An uncommon tibial plateau fracture: reverse Schatzker type IV
Chenyang XU ; Jinglei XU ; Ning CHANG ; Xianzhong MA ; Bin XU
Chinese Journal of Orthopaedics 2024;44(9):626-628
This report presents a rare case of a dislocated tibial plateau fracture. The patient sustained a closed fracture of the tibial plateau following a traffic accident, exhibiting a fracture pattern not fitting into any existing classification of tibial plateau fractures. Preoperative imaging revealed a lateral plateau fracture with medial dislocation of the knee joint and entrapment of the medial meniscus within the gap. The injury mechanism is hypothesized to involve external and internal rotation of the tibia relative to the femur, occurring during neutral or hyperextended positions of the knee joint. The patient's knee joint X-ray showed a fracture line passing through the lateral plateau, accompanied by medial dislocation of the knee joint, which mirrored the imaging of a Schatzker Type IV fracture dislocation caused by the classic mechanism of flexion varus and internal rotation. Hence, it was designated as a "reverse Schatzker type IV" tibial plateau fracture. Open reduction and internal fixation were performed on the 8th day post-injury, followed by knee joint stabilization with a hinge brace and guided functional exercises. Six months post-surgery, reevaluation indicated complete fracture healing and a knee flexion-extension range of 125°-5°.
7.Investigation and analysis of prevalence of musculoskeletal diseases among interventional surgeons in some top three hospitals in Tianjin
Huixing WANG ; Jingzhi LIU ; Wenting MA ; Xiaodong HUO ; Chenyang HAN ; Kemei SHI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(9):655-658
Objective:To analyze the prevalence and risk factors of musculoskeletal diseases among interventional surgeons in top three hospitals, and to provide suggestions for prevention of musculoskeletal diseases.Methods:In June 2022, a self-designed questionnaire was used to collect general information of doctors engaged in interventional surgery (121) and non-interventional surgery (124) in some top three hospitals in Tianjin. The standard version of the Nordic Musculoskeletal Questionnaire was used to investigate information related to musculoskeletal diseases. The prevalence and risk factors of musculoskeletal diseases among interventional and non-interventional surgeons were analyzed.Results:The prevalence of musculoskeletal diseases among interventional surgeons and non-interventional surgeons was 59.50% (72/121) and 62.90% (78/124) . Compared with non-interventional surgeons, interventional surgeons had a higher prevalence of musculoskeletal diseases in the shoulders and upper back, and a lower prevalence of musculoskeletal diseases in the waist. The differences were statistically significant ( P<0.05) . Multivariate logistic regression analysis showed that age, weekly time of physical exercise, time of intervention operation, and wearing protective clothing were independent risk factors for musculoskeletal diseases ( P<0.05) . Conclusion:The prevalence rate of musculoskeletal diseases among doctors engaged in interventional surgery is relatively high in some top three hospitals in Tianjin, and proper enhancement of physical exercise and shortening of interventional time are conducive to reducing musculoskeletal diseases.
8.Investigation and analysis of prevalence of musculoskeletal diseases among interventional surgeons in some top three hospitals in Tianjin
Huixing WANG ; Jingzhi LIU ; Wenting MA ; Xiaodong HUO ; Chenyang HAN ; Kemei SHI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(9):655-658
Objective:To analyze the prevalence and risk factors of musculoskeletal diseases among interventional surgeons in top three hospitals, and to provide suggestions for prevention of musculoskeletal diseases.Methods:In June 2022, a self-designed questionnaire was used to collect general information of doctors engaged in interventional surgery (121) and non-interventional surgery (124) in some top three hospitals in Tianjin. The standard version of the Nordic Musculoskeletal Questionnaire was used to investigate information related to musculoskeletal diseases. The prevalence and risk factors of musculoskeletal diseases among interventional and non-interventional surgeons were analyzed.Results:The prevalence of musculoskeletal diseases among interventional surgeons and non-interventional surgeons was 59.50% (72/121) and 62.90% (78/124) . Compared with non-interventional surgeons, interventional surgeons had a higher prevalence of musculoskeletal diseases in the shoulders and upper back, and a lower prevalence of musculoskeletal diseases in the waist. The differences were statistically significant ( P<0.05) . Multivariate logistic regression analysis showed that age, weekly time of physical exercise, time of intervention operation, and wearing protective clothing were independent risk factors for musculoskeletal diseases ( P<0.05) . Conclusion:The prevalence rate of musculoskeletal diseases among doctors engaged in interventional surgery is relatively high in some top three hospitals in Tianjin, and proper enhancement of physical exercise and shortening of interventional time are conducive to reducing musculoskeletal diseases.
9.General considerations for clinical trials design of gene therapy drug for β-thalassemia
Yunhong HUANG ; Xiao LIU ; Chenyang ZHAO ; Shuang LU ; Chenyan GAO ; Jun MA
Journal of Leukemia & Lymphoma 2022;31(11):697-700
β-thalassemia is a single-gene genetic disease caused by β globin gene mutations leading to the fact that red blood cells are unable to form normal adult hemoglobin, and then patients develop hemolytic anemia. Current treatment regimens mainly include allogenetic hematologic stem cell transplantation, symptomatic regular blood transfusions and the use of iron removers to reduce iron load. Some severe patients have quite poor prognoses and deadly consequences if not treated timely. Genetically modified autohematopoietic stem cells can provide a new treatment option for patients with β thalassemia, which may achieve a long-term and stable increase in hemoglobin level through a single dose, making one-time cure β-thalassemia possible. This paper reviews the key elements of clinical trial design for β-thalassemia gene therapy from the aspects of efficacy evaluation endpoints, clinical trial design, enrollment population, and subject monitoring in order to provide a reference for pharma-therapeutic research and development enterprises.
10.A buttress plate combined with Kirschner wires for Regan-Morrey type Ⅱ coronoid fracture in elbow terrible triad injury
Jinglei XU ; Xue BAI ; Chenyang XU ; Junsen DENG ; Ning CHANG ; Wanpo MIAO ; Xianda YI ; Xianzhong MA
Chinese Journal of Orthopaedic Trauma 2021;23(5):439-442
Objective:To evaluate the curative efficacy of a buttress plate combined with Kirschner wires for treatment of Regan-Morrey type Ⅱ coronoid fracture after elbow terrible triad injury.Methods:A retrospective study was conducted of the 20 patients who had been surgically treated for Regan-Morrey type Ⅱ coronoid fracture after elbow terrible triad injury from August 2014 to August 2018 at Department of Pelvic Trauma, Henan Luoyang Orthopedic-Traumatological Hospital. They were 12 men and 8 women, aged from 18 to 60 years (average, 39 years), with 6 left and 14 right sides affected. All the coronoid fractures were fixated with Kirschner wires plus a buttress plate through the anterior approach, the radial head and lateral collateral ligaments (LCL) were repaired through the posterolateral approach, and the medial collateral ligament (MCL) was repaired or fixated with a hinged external fixator if necessary. The curative efficacy was evaluated at the last follow-up by range of motion (ROM) of the elbow, Mayo elbow performance score (MEPS), American Shoulder and Elbow Surgeons Scale (ASES) and radiographs of the elbow. Complications were also recorded.Results:The mean follow-up time was 18 months (from 12 to 24 months) and the mean healing time 5 months. At the last follow-up, ROM in flexion and extension of the affected elbow joint averaged 132.5°, ROM in elbow pronation-supination 150°, MEPS 88, and ASES 87. No subluxation or dislocation occurred after elbow surgery. The fracture of coronoid process was slightly displaced in one case but eventually healed without affecting any elbow function; fat liquefaction occurred around the posterolateral incision in 2 cases but healed after debridement; traumatic arthritic changes occurred in 5 patients but no significant dysfunction of the elbow was observed.Conclusion:A buttress plate combined with Kirschner wires can lead to fine curative efficacy for Regan-Morrey type Ⅱ coronoid fracture after elbow terrible triad injury.

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