Objective To investigate the effects of the leflunomide active metabolite (A771726) on the expression of phorbol-12-myristate-13-acetate (PMA) -induced CD147, matrix metallo-proteinase (MMP)-2 and MMP-9 on THP-1 cells. Methods THP-1 cells were cultured in RPMI-1640 medium supplemented with 10％ fetal bovine serum. For all experiments, THP-1 cells were cultured at an initial density of 5×105/ml. Before A771726 treatment, cells were cultured with serum-free RPMI-1640 medium for 12 h, THP-1cells were co-cultured with PMA at three different concentrations of A771726 (5, 15 , 45 μg/ml) for 24 h.The mRNA expression of CD147, MMP-2 and MMP-9 was measured by real-time PCR. CD147 expression on the cells were evaluated by flow cytometric analysis. The activity of MMP-2 and MMP-9 were evaluated by gelatin zymography. Statistical differences among the groups were tested by one-way ANOVA or KruskalWallis test. Results The expression of CD147, MMP-2 and MMP-9 were upgraded by the PMA. The expression of CD147 on THP-1 cells was inhibited significantly by A771726 in a dose-dependent pattern (P＜0.01). The mean fluorescence intensity (MFI) of CD147 in positive control group was 109.5±3.8, the MFI in A771726 (5, 15, 45 μg/ml) group were 73.3±2.5, 64.5±2.3, 40.9±2.7, respectively. The expression of MMP-2, MMP-9 mRNA and the activity of MMP-2, MMP-9 in the supernatant was inhibited significantly by A771726 (P＜0.01). The expression of CD147 mRNA was not inhibited significantly by A771726 (P＞0.05).Conclusion Leflunomide active metabolite (A771726) can inhibit the expression of PMA-induced CD147,MMP-2 and MMP-9 on THP-1 Cells.

Objective To observe the effect of infliximab combination therapy on the expression of CD147 on the peripheral CD14+ monocytes of active rheumatoid arthritis (RA) patients. Methods Thirty active RA patients who were refractory to MTX treatment were randomized into three groups (group A, B, C) with the proportion of 3:1:1. Group A and B received four or three infusions of infliximab (3 mg/kg), group C received four infusions of placebo. All three groups were added to a stable background of MTX. The mean fluorescence intensity (MFI) of CD147 expression on the peripheral CD14+ monocytes of RA patients and normal healthy controls were detected by flow cytometry analysis. Clinical and laboratory parameters were assessed before each infusion. One-way ANOVA, Kruskal-Wallis the MFI of CD147 expression at week 18 (P<0.05). Marked differences were observed between the infliximab + MTX group and the placebo + MTX group on the change of the MFI of CD147 expression from baseline to week 18 (P<0.05).Conclusion CD147 expression on the peripheral CD14+ monocytes of active RA patients is increased, and combination therapy of infliximab and MTX can inhibit the expression.

Objective To evaluate morphological structure of uterosacral ligament (USL) and cardinal ligament (CL) in patients with severe pelvic organ prolapse (POP) by MRI technology, and to analysis and discuss its clinical significance. Methods From November 2013 to February 2014 in Peking University People′s Hospital, 26 elderly patients withⅢ-Ⅳdegree of POP were selected as the POP group and 18 healthy elderly volunteers were selected as the control group during the same period. Pelvic MRI examination were performed in the two groups. The morphological characteristics of left and right side of the uterosacral-cardinal ligament on MRI and the attachment site of the starting and ending points between two group were described and compared. Results In POP group, 25 cases of left USL starting point were located in the sacrospinous ligament/coccygeal muscle complex [58% (15/26)] or coccygeal muscle [38%(10/26)], ending point were located in the cervix and vagina [58%(15/26)] or cervix [38%(10/26)];24 cases of right USL starting point were located in the sacrospinous ligament/coccygeal muscle complex [31%(8/26)]or coccygeal muscle [62%(16/26)], 26 cases of right USL ending point were located in the cervix and vagina [62% (16/26)] or cervix [38% (10/26)]; the left and right CL in the POP group and the control group were both from the sacroiliac joint at the top of the greater sciatic foramen from the ipsilateral pelvic side wall;1 case (4%, 1/26) of left CL in the POP group completely connected to the bladder, 10 cases (38%, 10/26) partly connected to the bladder;14 cases (54%, 14/26) of right CL partly connected to the bladder, the rest ending points of left and right CL were located in cervix and (or) vagina. In the control group, 17 cases of left USL starting point were located in the sacrospinous ligament/coccygeal muscle complex (10/18) or coccygeal muscle (7/18), ending point were located in the cervix and vagina (12/18) or cervix (6/18);18 cases of right USL starting point were located in the sacrospinous ligament/coccygeal muscle complex (10/18) or coccygeal muscle (8/18), ending point were located in the cervix and vagina (13/18) or cervix (5/18);8 cases (8/18) of left CL partly connected to the bladder;15 cases (15/18) of right CL partly connected to the bladder, the rest ending points of left and right CL were located in cervix and (or) vagina. There was no significant difference between the two groups on the starting and ending points (P>0.05). Conclusions The observation of MRI could be consistent with the clinical anatomy on the starting and ending points, direction of travel in the uterosacral-cardinal ligament. The starting and ending points of the left and right side USL and the ending points of the left and right side CL are not completely symmetrical, the variation degree is large, some CL could be completely or partly inserted to the bladder.

Objective To establish the finite element model of uterosacral ligament (USL) and cardinal ligament (CL) and analyze the stress distribution and deformation with USL and CL under different working conditions. Methods Patients with stage Ⅲ-Ⅳpelvic organ prolapse (POP) and healthy female volunteers were selected for research subject, and divided into anterior uterus group and posterior uterus group. Two POP patients and two volunteers were selectd into the anterior uterus group and posterior uterine group respectively. Pelvic MRI scan was performed in two groups. Based on the original MRI data sets, the finite element model of USL and CL was constructed by using the software such as the Mimics, and the stress distribution and deformation of USL and CL were simulated. Results Under the premise of the elastic modulus fixed and three different working conditions such as 60 cmH2O, 99 cmH2O and 168 cmH2O (1 cmH2O=0.098 kPa) with abdominal pressure generated by maximum Valsalva maneuver, according to the present conditions and the simulation, the trend was analyzed: the stress and deformation of the uterus, anterior vaginal wall, USL and CL in two groups were mainly distributed in the middle and lower part of the anterior vaginal wall or the ligament and the cervix-vagina junction, the maximum stress and the maximum displacement were mainly concentrated in the lower region of the anterior vaginal wall. With increasing of abdominal pressure generated by the maximum Valsalva maneuver, the maximum stress values of the POP patient in anterior uterus group under three different working conditions were: 0.027 9, 0.046 0, 0.078 0 MPa, and the maximum displacement values were: 9.145 5, 15.090 0, 25.607 0 mm. The maximum stress values of the volunteer in anterior uterus group under three different working conditions were:0.012 6, 0.020 8, 0.035 3 MPa, and the maximum displacement values were: 1.816 7, 2.997 5, 5.086 7 mm. The maximum stress values of the POP patient in posterior uterine group under three different conditions were: 0.069 4, 0.114 6, 0.194 5 MPa, and the maximum displacement values were:11.658 0, 19.236 0, 32.643 0 mm. The maximum stress values of the volunteer in posterior uterus group under three different working conditions were:0.009 1, 0.015 1, 0.025 6 MPa, and the maximum displacement values were:2.581 6, 4.259 6, 7.228 4 mm. The maximum stress values and the maximum displacement values were all increased with increasing of abdominal pressure in the two groups. The maximum stress values and the maximum displacement values of the POP patients were greater than those of volunteers. Under different working conditions, the maximum stress values and maximum displacement values of the posterior uterus POP patient were all greater than those of the anterior uterus POP patient. Conclusions The finite element model of USL and CL is completely based on the MRI technology and the model is real and reliable. The increase of abdominal pressure will produce a larger stress and deformation of USL and CL, which is one of the reasons causing the injury of the ligament.

Objective:To analyze the trend relevant factors leading to death and their patterns over a 10-year period in inpatients with connective tissue diseases (CTDs).Methods:All clinical data about death in inpatients with CTDs were retrospectively reviewed between 2005 and 2014 at the Department of Rheumatology and Immunology in Xiangya Hospital of Central South University.Results:In the 10-year time period,the overall hospital mortality was 15.689‰.The disease itself accounted for 44.71% of the total causes of death,infection accounted for 42.94%,and comorbidities accounted for 12.35%.The constituent ratio of deaths and the average hospital mortality caused by the disease itself declined gradually year by year,and the constituent ratio of deaths caused by infection and comorbidities increased gradually year by year (P<0.05).In 2013-2014,infection was the leading cause of death,which accounted for 51.06%.The survival time for CTDs inpatients with interstitial lung disease (ILD) was shorter than that of CTDs inpatients without ILD,and even the risk of death was 1.722 times of the latter.The proportion of deaths caused by the disease itself was the highest in systemic sclerosis and systemic lupus erythematosus,that by infection was the highest in idiopathic inflammatory myopathy (IIM),and that by comorbidities was the highest in rheumatoid arthritis.Conclusion:The proportion of deaths and the hospital mortality in CTDs inpatients caused by the disease itself show a declining trend,while the proportion of deaths caused by infection and comorbidities increase.CTDs patients with ILD have shorter survival time and an increase in risk of death.

Objective:To investigate the awareness and application of exercise prescription among general practice faculty in Taiyuan City, and to analyze the related factors.Methods:A questionnaire survey on the awareness and application of exercise prescriptions was conducted from July to September 2021 among general practice faculty in Taiyuan City selected by stratified random sampling method. The influencing factors of awareness and application were analyzed with logistic regression.Results:A total of 589 general practice faculty were enrolled in the study, 342 of whom were females (58.06%). The overall awareness rate of exercise prescription was 38.74% (1 369/3 534); the awareness rate of basic knowledge was 56.08% (991/1 767) and the awareness rate of core knowledge was 21.39% (378/1 767). Logistic analysis showed that specialty as general practitioner ( OR=1.66, 95% CI:1.07-2.57, P=0.024), experience of exercise prescriptions ( OR=2.07, 95% CI:1.37-3.12, P=0.001) and willingness of public promotion of exercise benefits ( OR=2.08, 95% CI:1.05-4.15, P=0.037) were factors related to higher awareness of exercise prescription. The survey showed that 231 responders (39.22%) had given patients exercise guidance, among whom 125 (54.11%) gave oral and specific practice guidance, 206 (89.18%) would ask patients to perform health screening before exercise, and 184 (79.65%) performed health fitness evaluation. The knowledge used for guidance was mostly from textbooks or related guidelines (42.42%, n=98), but none of them had prescribed standardized exercise prescriptions. Conclusions:The survey shows that the knowledge and application rate is relatively low among general practice faculty in Taiyuan City. It is necessary to strengthen the training of exercise prescription for them.

Resistance exercise plays an important role in management of cardiovascular disease and blood sugar control;and in improvement of skeletal muscle health and old-age debility. The purpose of this review is to summarize the preventive and therapeutic effects of resistance exercise on various chronic diseases, to improve the knowledge and awareness of the general practitioners for comprehensive understanding of the role of resistance exercise and to provide exercise guidance for patients with chronic diseases.

Frailty is a nonspecific state with the decline of physiological reserve leading to the increased vulnerability and decreased anti-stress ability in the elderly. Frailty can cause cognitive impairment and physical function decline, and increase the risk of a series of adverse events such as hospitalization, disability and death in the elderly. Studies have shown that early intervention can reverse debilitating condition; therefore, early and timely intervention of frailty has important practical significance for improving the health status of the elderly and reducing the pressure on the medical system. This article reviews frailty interventions and their effects in the elderly, including sports intervention, nutrition intervention, drug intervention and integrated intervention, focusing on the research progress of frailty intervention, to provide reference for clinical management of frailty in the community-dwelling elderly.

The prevention and treatment of rare diseases is an important public health issue in China. Rare diseases are characterized by diverse types, complex conditions, and heavy burdened to patients, leading to a series of issues in the urgent demand in prevention and treatment of rare diseases in terms of individuals′ health and the national responsibilities. Related legislation is an effective way to promote multi-disease prevention and treatment of rare diseases, and patients′ protection in multi-level. We tease out and analyze the legal system on national and local level related to rare diseases, and recommend the coping strategies and give suggestions to improve and optimize the legal system for the prevention and treatment of rare diseases from the three dimensions of completeness, normalization and feasibility of the legislation, hoping to improve the competence of China′s rare disease prevention and treatment and raise the level of protection for the patients.

Pharmacoeconomic evaluation is the essential supporting information for the inclusion of rare disease drugs into medical insurance in China. The accurate measurement of the health state utility of rare diseas is of practical significance to the development of rare disease pharmacoeconomic evaluation. Based on the review of pharmacoeconomic evaluation requirements for rare diseases in some countries/regions, we systematically retrieved the published studies on the measurement of health state utility for 121 rare diseases in China and other countries and regions. We identified 17 591 papers in the initial review, and later selected 230 after screening. We also made a comprehensive analysis of the quality of literature, evaluation content and use of tools for measuring health state utility in rare diseases in China. Finally, we analyzed the challenges in measurement in terms of population, instruments use, and application of results and made recommendations based on analysis, hoping to provide reference for the development of rare disease health state utility measurement studies in China.