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.

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.

Objective : To explore the correlation between uteroglobulin-related protein 1(UGRP1) and primary hypothyroidism. Methods : Ninety-six patients with primary hypothyroidism were selected, including 66 patients with positive thyroid peroxidase antibodies(TPOAb) or anti-thyroglobulin antibodies(ATG) as the antibody-positive group, 30 patients with negative thyroid autoantibodies as the antibody-negative group, and 96 healthy people as the control group. The general clinical data, thyroid-related indicators and serum UGRP1 levels were compared among these three groups. Human thyroid normal cells(NTHY-ORI 3-1) were transfected with plasmids in vitro, thus establishing the control group as well as the UGRP1 group. Enzyme linked immunosorbent assay(ELISA) was used to detect and compare the T4 level in the cell culture supernatant. Results : The differences in thyroid stimulating hormone(TSH), TPOAb and ATG among the three groups were statistically significant(P<0.05). The serum UGRP1 levels in the antibody-positive(303.97±156.00) pg/ml and antibody-negative groups(352.13±188. 37) pg/ml were higher than those in the control group( 237. 54 ± 137. 20) pg/ml,and the differences between the groups were statistically significant( P = 0. 005). Meanwhile,there was no statistically significant difference between the antibody-positive and antibody-negative groups. Multi-factor Logistic regression analysis showed that UGRP1 was the risk factor for the occurrence of primary hypothyroidism( OR = 1. 004,95% CI: 1. 001-1. 007,P =0. 007). The difference between the control group and UGRP1 group in T4 concentration secreted by human thyroid normal cells was not statistically significant. Conclusion Serum UGRP1 levels increase in patients with primary hypothyroidism,and the high expression of UGRP1 may have no direct relation to the function of thyroid cells secreting T4.

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.

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.

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.

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°.

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.

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.

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.