ObjectiveTo establish a neuroinflammation-based obesity and depression comorbidity （COM） model in mice and explore the pharmacodynamics and preliminary pharmacological mechanism of tripterine on COM mice. MethodC57BL/6J mice were randomly divided into a normal group （Chow）， a diet-induced obesity group （DIO）， and a COM group. The mice in the COM group were fed on a high-fat diet and chronically stressed with moist litter for 12 weeks to establish the COM model. C57BL/6J mice were randomly divided into a Chow group， a COM group， and a tumor necrosis factor-α（TNF-α） knock-down group. In the TNF-α knock-down group， TNF-α shRNA adeno-associated virus was injected into the amygdala through brain stereotaxis， and the expression of TNF-α in the amygdala was down-regulated. C57BL/6J mice were randomly divided into a Chow group， a DIO group， a DIO + low-dose tripterine group （0.5 mg·kg^-1）， a DIO + high-dose tripterine group （1.0 mg·kg^-1）， a COM group， a COM + low-dose tripterine group （0.5 mg·kg^-1）， and a COM + high-dose tripterine group （1.0 mg·kg^-1）. The body weight， food intake， glucose tolerance， white/brown fat ratio， serum total cholesterol （TC）， triglyceride （TG）， and high-/low-density lipoprotein cholesterol （HDL-C and LDL-C） content were recorded， and obesity of mice in each group was evaluated. Forced swimming test （FST）， tail suspension test （TST）， and open field test were used to evaluate the degree of depression of mice in each group. Immunofluorescence staining was used to detect the protein expression levels of neuropeptide Y， tryptophan hydroxylase 2 （TPH2）， and brain-derived neurotrophic factor （BDNF） in various brain nuclei of mice. Correlation analysis was used to detect the correlation of obesity and depression indexes. ResultThe comparison of the Chow group and the DIO group indicated that COM mice showed obesity and depression. To be specific， obesity was manifested as increased body weight and food intake （P<0.05， P<0.01）， as well as increased NPY expression in the central amygdala， and depression was manifested as prolonged immobility time in FST and TST （P<0.01）， and reduced TPH2-positive 5-hydroxytryptamine neurons in the dorsal raphe nucleus （DRN） and basolateral nucleus of the amygdala （BLA）. The down-regulation of TNF-α protein in BLA of COM mice shortened the immobility time in FST and TST （P<0.05， P<0.01）， increased TPH2/BDNF-positive neurons in BLA， and showed no significant changes in obesity. In DIO mice， the administration of 0.5 mg·kg^-1 tripterine for 9 days significantly decreased the 60 min blood glucose in glucose tolerance （P<0.01） and food intake （P<0.05）. In COM mice， 1.0 mg·kg^-1 tripterine was administered for 14 days to significantly decrease 30 min blood glucose in glucose tolerance （P<0.01）， and food intake （P<0.05）， and immobility time in TST （P<0.01）， increase TPH2-BDNF double-labeled cells in BLA and DRN， and reduce the area of TMEM119-stained cells. ConclusionThe model of obesity and depression comorbidity can be properly induced in mice under the condition of dual stress of energy environment. Tripterine can effectively interfere with obesity-depression comorbidity， and its mechanism may be related to the inhibition of central nervous system inflammation.

ObjectiveTo evaluate the clinical efficacy and safety of Tripterygium wilfordii polyglycoside tablets （TWP） in the treatment of rheumatoid arthritis （RA） in the real world. MethodDiagnosis and treatment data of patients with RA in Chinese medicine rheumatology registration research information platform information database （CERTAIN） from January 1，2019 to January， 2024 were collected. According to the inclusion and exclusion criteria， data were screened. The included data were divided into an exposure group and a control group according to the use of TWP or not. Propensity score matching （PSM） was used in both groups to keep the baseline balanced and comparable. The disease activity score （DAS28-ESR） of 28 joints based on the erythrocyte sedimentation rate （ESR）before and after treatment was compared between the two groups， as well as health assessment questionnaire （HAQ），visual analogue scale （VAS），tender joint count （TJC），swollen joint count （SJC）， patient's global assessment （PGA），evaluator's global assessment （EGA），laboratory indexes， clinical curative effect， and adverse reactions. ResultA total of 3 978 patients were included，including 929 in the exposure group and 3 049 in the control group. Before PSM，there were significant differences in demographic information，DAS28-ESR score，PGA，EGA，HAQ，VAS scores，SJC， and TJC between the two groups （P<0.05）. After successful PSM matching，922 patients in the exposure group and 922 patients in the control group were included. There was no significant difference in demographic information and DAS28-ESR between the two groups before treatment，and the differences in other indexes between the two groups decreased to varying degrees. After treatment，the DAS28-ESR，PGA，EGA，HAQ，SJC，TJC，VAS scores， ESR，and IgG immune index of the two groups were significantly lower （P<0.01）. Compared with those in the control group after treatment，the DAS28-ESR，PGA，EGA，HAQ，VAS scores， and ESR in the exposure group after treatment decreased more significantly （P<0.05，P<0.01）. There was no significant difference in TJC in the exposure group after treatment. However， TJC in the exposure group was significantly higher than that in the control group before treatment （P<0.05）. In terms of TJC reduction，the exposure group performed better than the control group. There was no significant difference in SJC and IgG between the exposure group and the control group after treatment. After treatment，the clinical symptoms of poor appetite，insomnia and many dreams，upset，fatigue，and fear of wind and cold in the two groups were improved. Except that the proportion of women in the exposure group was higher than that in the control group （P<0.01），there was no significant difference in the incidence of other adverse reactions between the two groups after treatment. ConclusionTWP to treat RA can effectively reduce DAS28-ESR，PGA，EGA，HAQ，TJC，and VAS scores and improve the general symptoms. Except for the women at childbearing age with fertility requirements that TWP is not applicable，it shows good security.