Rheumatoid arthritis belongs to arthralgia syndrome in the theory of traditional Chinese medicine， and cold-dampness obstruction syndrome and dampness-heat obstruction syndrome are core syndromes and main syndrome differentiation types of this disease. Fine therapeutic effects have been obtained in the long-term clinical practice of many famous traditional Chinese medicine practitioners following the syndrome differentiation and treatment based on the guiding principles of cold and heat. To adapt to the clinical diagnosis practice of combining disease differentiation and syndrome differentiation， and to better carry out basic research on integrated Chinese and Western medicine and preclinical study on new traditional Chinese medicines， Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-Dampness Obstruction Syndrome and Dampness-Heat Obstruction Syndrome （hereinafter referred to as the Guidelines） were compiled by our research group， in cooperation with the renowned experts in research fields including traditional Chinese medicine， clinical medicine， zoology and evidence-based medicine， which provide a meaningful reference for scientific research， teaching and clinical applications. The compilation process of the Guidelines was guided by the theory of disease and syndrome integration and the principles of "evidence takes the main place， consensus plays an auxiliary role， and experience serves as the reference". Based on the comprehensive evaluation of pathogenesis homology， behavioral phenotypic consistency， and drug treatment predictability compared between animal models and human diseases， by the nominal group method， "recommendations" were formed for recommendations supported by evidence， and "consensus recommendations" were formed for recommendations not supported by evidence. Guidelines were formed involving content such as animal types， arthritis modeling methods， external stimulation conditions， and modeling assessment indicators during the establishment of the animal models of rheumatoid arthritis with cold-dampness obstruction syndrome and dampness-heat obstruction syndrome. The Guidelines are applicable for the disease and syndrome research on rheumatoid arthritis， investigation of therapeutic mechanisms， and development of new traditional Chinese medicine. The Guidelines also provide a reference for the establishment of guidelines on other types of diseases and syndromes combined with animal models to further promote the modernization of traditional Chinese medicine research and its integration with international academic development.

The Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome （hereinafter referred to as the Guidelines） （No. T/CACM1567-2024） was published by Chinese Association of Chinese Medicine on January 11， 2024. To assist researchers and medical workers in understanding and applying the Guidelines more accurately， and also to provide reference and assistance for the establishment of guidelines on other types of diseases and syndromes combined with animal models， this paper made a declaration of the workflow， technological links， development references， promotion of its application and after-effect evaluation of the Guidelines that has been made according to the requirements of "Draft Group Standard of the Standardization Office of the Chinese Association of Traditional Chinese Medicine".

Objective To explore the effect of Internet+cardiac rehabilitation on hypertension patients with coronary heart disease.Methods 80 patients with hypertension and coronary heart disease admitted to our hospital from January 2022 to April 2023 were randomly divided into the combined group(n=40)and the conventional group(n=40).Both groups were given routine cardiac rehabilitation interventions.The combined group combined adoptionof the Internet for continuous interventionson the basis of routine cardiac rehabilitation interventions.Compare the oxygen uptake,blood pressure,compliance,and self-management scores between two groups before intervention and three months after discharge.Results The AT Mets,AT VO2,peak VO2,and expected value compliance ratio in the combined group were all higher than those in the conventional group(P<0.05);The systolic and diastolic blood pressure in the combination group were lower than those in the control group,and the proportion of complete compliance was significantly higher than that in the control group(P<0.05);The self-management scores of the joint group were higher than those of the conventional group(P<0.05).Conclusion The continuous interventions of Internet plus cardiac rehabilitation can control the blood pressure of patients with hypertension and coronary heart disease,and patients'compliance behavior is significantly im-proved,andthus improving patients'self-management ability,which can be used for reference and promotion in clinical practice.

Objective To delve into the causal relationship between 211 gut microbiota and sepsis employing bidirectional Mendelian randomization(MR).Methods The gut microbiota genome-wide association study(GWAS)data from the Microbiome Genetics Consortium(MiBioGen,n = 18 340)and sepsis GWAS data from the FinnGen(n = 286 146)were harnessed for this study.Initially,single nucleotide polymorphisms(SNP)significantly associated with the relative abundance of 211 gut microbiota taxa were identified as instrumental variables using predefined selection criteria.The primary analytical approach was characterized by the application of inverse variance weighting(IVW),with the effect measure represented by the odds ratio(OR)to assess the results of MR.To ensure precision and reliability,analyses were conducted,including leave-one-out analysis,heterogeneity testing,and tests for pleiotropy at both coherent and incoherent levels.Results The increased risk of sepsis was associated with the elevated abundance of Collinsella[OR = 1.28,95%confidence interval(95%CI)was 1.06-1.56,P = 0.01]and Ruminococcus(OR = 1.19,95%CI was 1.05-1.35,P = 0.005).Furthermore,a protective effect against the development of sepsis was observed in association with the increased abundance of Prevotella(OR = 0.88,95%CI was 0.79-0.97,P = 0.01)and Firmicutes(OR = 0.86,95%CI was 0.75-0.996,P = 0.04).No obvious heterogeneity and irrelevant level pleiotropy were detected.Conclusion Collinsella and Ruminococcus increase the risk of sepsis,while Prevotella and Firmicutes have protective effects against sepsis.

OBJECTIVE: Autologous blood acupoint injection has practiced for treatment of various diseases, but its therapeutic mechanism remains unknown. This study aimed to explore the histological changes in the acupoint area after blood injection. METHODS: Blood samples (0.1 mL) collected from donator mice was injected in the recipient mice at the acupoint of left Zusanli (ST- 36). At 0, 6, 12, 24, 48, 72 and 96 h after the injection (3 mice at each time point), peripheral blood and muscular tissue were collected from the injection site for blood cell classification and histological study with HE staining. RESULTS: White blood cells and lymphocytes tended to increase but platelets tended to decrease at the acupoint after blood injection, but these changes were not statistically significant. Within 24 h after blood injection, acute inflammation occurred at the acupoint, and the injected blood components were infiltrated by neutrophils; a small number of monocytes were observed at the injection site, where red blood cells gradually disappeared. From 24 to 96 h, the injected area showed chronic inflammation with infiltration by mononuclear cells, macrophages, and lymphocytes, and the number of fibroblasts increased and neutrophils decreased gradually over time; the local muscle fibers were destroyed, and proliferation of fibrous tissue could be seen. CONCLUSIONS Blood injection at the acupoints can mimic the process of hematoma absorption in the muscular tissue, and local inflammation is initiated to engulf and clear the blood components, which may be the basis for the therapeutic effects induced by acupoint stimulation.

Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.

Objective:To compare the expression levels of absent in melanoma 2 (AIM2) inflammasome pathways in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial specimens.Methods:Synovial tissue samples were collected from 41 RA and 26 OA patients, respectively. Horseradish peroxidase immunohi stochemical staining was used to detect AIM2 inflammasome pathway-related proteins, including AIM2, apoptosis-associated speck-like protein containing a CARD(ASC), caspase-1, and interleukin-1 (IL-1β). A semi-quantitative score (H-score) was performed according to the degree of positiveness. Correlation analysis between H-score results and clinical indicators of erythrocyte sedimentation tate (ESR) and C-reactive protein (CRP) were performed. The H score between RA and OA was analyzed by t test and Spearman correlation analysis were utilized for correlation analysis between H score and ESR and CRP.Results:The H scores of AIM2 protein in RA synovial tissues was (132±7) and (54±8) in OA synovial tissues ( t=7.42, P<0.01). The H scores of ASC protein in RA synovial tissues was (107±9) and (74±6) in OA synovial tissues ( t=2.36, P<0.05). The H scores of caspase-1 protein in RA synovial tissues was (99±5) and (74±10) in OA synovial tissues ( t=2.15, P<0.05). The H scores of IL-1β protein in RA synovial tissues was (118±11) and (76±7) in OA synovial tissues ( t=3.30, P<0.05) . In the correlation analysis, AIM2 was positively correlated with ESR [ r=0.74, P<0.01, 95% CI(0.38, 0.9)], and ASC was positively correlated with ESR [ r=0.5, P<0.05, 95% CI(0.16, 0.74)], IL-1β was positively correlated with ESR [ r=0.62, P<0.05, 95% CI (0.31, 0.81)], and the difference was statistically significant ( P<0.05). At the same time, AIM2 was positively correlated with CRP [ r=0.65, P<0.05, 95% CI(0.25, 0.86)]; ACS was positively correlated with CRP [ r=0.42, P<0.05, 95% CI(0.05, 0.69)]. IL-1β was positively correlated with C-reactive Protein [ r=0.41, P<0.05, 95% CI(0.05, 0.67)] and positively correlated with C-reactive protein, and the difference was statistically significant ( P<0.05). Conclusion::The expression of AIM2 inflammasome pathway-related proteins in RA synovium, including AIM2, ASC, caspase-1, and IL-1β, is higher than that of OA and are positively correlated with disease activity. Activation of AIM2 inflammasome pathway may be associated with the pathogenesis of RA disease activity.

Objective To detect the spatial clustering and high risk areas of pulmonary tuberculosis (PTB) in Sichuan province in 2018 and,to compare the effects of application on both SaTScan 9.4.1 software and FleXScan 3.1.2 software to detect the PTB spatial clusters.Methods Geographic information database was established by using the incidence data of PTB and demographic data reported in the'China disease prevention of infectious disease reporting information management system'in Sichuan province in 2018.Spatial clustering analysis was conducted using the Poisson model in software SaTScan 9.4.1 and FleXScan 3.1.2 to detect the high risk areas of PTB by software ArcGIS 10.5.Differences of clusters locations and scopes in the two scanning methods were compared.Results The reported incidence rate of PTB was 57.34/100 000 (47 601 cases) in Sichuan province in 2018,presenting an obvious clustering distribution.SaTScan and FleXScan scanned 8 and 10 clusters showed statistically significant differences (P＜0.05),with log-likelihood ratio (LLR) as 24.62-2 416.05 and 1.48-2 618.96,respectively.Results from scanning of the two methods showed that the most likely clusters appeared in the Daliangshan and Xiaoliangshan of Liangshan Yi ethnic aggregation areas.The other clustering areas would include some minority areas in the western Sichuan plateau,detected by both two methods differences in the shape and scope of the clustering were detected by both methods.The clustering scopes detected by SaTScan covered some counties,in which the actual incidence was not high.FleXScan could distinguish the clusters and detect more irregular shaped clusters.Conclusions Obvious spatial clusters of PTB distribution were found in Sichuan in 2018.Areas of Daliangshan,Xiaoliangshan and the minority areas in Western Sichuan plateau appeared at high risk,suggesting these were the key areas for prevention and control.FleXScan seemed more conducive in accurately distinguishing the "cold spot" areas in the highly aggregated areas,and more suitable for the application of spatial clustering detection for TB,in Sichuan province.

The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.

OBJECTIVE: To compare the histopathological features of the synovium between rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: We retrospectively analyzed the synovial specimens obtained after synovial surgery in 72 cases of RA and 24 cases of OA. Two independent pathologists reviewed the sections of the synovial tissues with HE staining, quantitatively scored the degree of fibroblast-like synoviocyte (FLS) hyperplasia, vascular hyperplasia, fibroplasia, and lymphocyte infiltration, and examined the presence plasma cell infiltration. The pathological morphology of the synovial tissues was evaluated in relation with the clinical data of the patients. RESULTS: Pannus formation was also detected in the synovium of OA patients, which showed a lesser degree of OA-FLS hyperplasia, fibrosis and lymphocyte infiltration and a significantly lower rate of plasma cell infiltration compared with the pannus in RA patients. Vascular proliferation was also milder in the pannus of OA patients than in RA pannus, but the difference was not statistically significant. In OA patients, the pannus could be observed under a microscope and was difficult to distinguish from that in RA patients. CONCLUSIONS Pannus formation occurs also in the synovium of OA patients but with milder FLS hyperplasia, fibrosis and lymphocyte infiltration and a lower rate of plasma cell infiltration compared with the pannus in RA patients. These differences in the pannus between OA and RA can be of potential value in the diagnosis and treatment of the patients.
Arthritis, Rheumatoid ; Cells, Cultured ; Humans ; Osteoarthritis, Knee ; Retrospective Studies ; Synovial Membrane