The standardized diagnosis and treatment of rheumatoid arthritis / 中华内科杂志

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation of the joints with high risk of disability. In recent years, remarkable progress has been made towards the diagnosis and treatment of RA, and the international RA guidelines have been also kept updated. Nevertheless, there are many challenges in China, especially inadequate number of rheumatologists and insufficient experience in the diagnosis and treatment of RA. Therefore, Chinese Rheumatology Association drafted the standardized diagnosis and treatment of RA based on the available evidence, so as to improve the management of RA patients in China.

Structure-based discovery of orally efficient inhibitors via unique interactions with H-pocket of PDE8 for the treatment of vascular dementia

Our previous study demonstrated that phosphodiesterase 8 (PDE8) could work as a potential target for vascular dementia (VaD) using a chemical probe 3a. However, compound 3a is a chiral compound which was obtained by chiral resolution on HPLC, restricting its usage in clinic. Herein, a series of non-chiral 9-benzyl-2-chloro-adenine derivatives were discovered as novel PDE8 inhibitors. Lead 15 exhibited potent inhibitory activity against PDE8A (IC50 = 11 nmol/L), high selectivity over other PDEs, and remarkable drug-like properties (worthy to mention is that its bioavailability was up to 100%). Oral administration of 15 significantly improved the cAMP level of the right brain and exhibited dose-dependent effects on cognitive improvement in a VaD mouse model. Notably, the X-ray crystal structure of the PDE8A-15 complex showed that the potent affinity and high selectivity of 15 might come from the distinctive interactions with H-pocket including T-shaped π-π interactions with Phe785 as well as a unique H-bond network, which have never been observed in other PDE-inhibitor complex before, providing new strategies for the further rational design of novel selective inhibitors against PDE8.

Fucoxanthin regulates Nrf2/Keap1 signaling to alleviate myocardial hypertrophy in diabetic rats / 南方医科大学学报

OBJECTIVE@#To investigate the protective effect of fucoxanthin (FX) against diabetic cardiomyopathy and explore the underlying mechanism.@*METHODS@#Rat models of diabetes mellitus (DM) induced by intraperitoneal injection of streptozotocin (60 mg/kg) were randomized into DM model group, fucoxanthin treatment (DM+FX) group and metformin treatment (DM+ Met) group, and normal rats with normal feeding served as the control group. In the two treatment groups, fucoxanthin and metformin were administered after modeling by gavage at the daily dose of 200 mg/kg and 230 mg/kg, respectively for 12 weeks, and the rats in the DM model group were given saline only. HE staining was used to examine the area of cardiac myocyte hypertrophy in each group. The expression levels of fibrotic proteins TGF-β1 and FN proteins in rat hearts were detected with Western blotting. In the cell experiment, the effect of 1 μmol/L FX on H9C2 cell hypertrophy induced by exposure to high glucose (HG, 45 mmol/L) was evaluated using FITC-labeled phalloidin. The mRNA expression levels of the hypertrophic factors ANP, BNP and β-MHC in H9C2 cells were detected using qRT-PCR. The protein expressions of Nrf2, Keap1, HO-1 and SOD1 proteins in rat heart tissues and H9C2 cells were determined using Western blotting. The DCFH-DA probe was used to detect the intracellular production of reactive oxygen species (ROS).@*RESULTS@#In the diabetic rats, fucoxanthin treatment obviously alleviated cardiomyocyte hypertrophy and myocardial fibrosis, increased the protein expressions of Nrf2 and HO-1, and decreased the protein expressions of Keap1 in the heart tissue (P < 0.05). In H9C2 cells with HG exposure, fucoxanthin significantly inhibited the enlargement of cell surface area, lowered the mRNA expression levels of ANP, BNP and β-MHC (P < 0.05), promoted Nrf2 translocation from the cytoplasm to the nucleus, and up-regulated the protein expressions its downstream targets SOD1 and HO-1 (P < 0.05) to enhance cellular antioxidant capacity and reduce intracellular ROS production.@*CONCLUSION@#Fucoxanthin possesses strong inhibitory activities against diabetic cardiomyocyte hypertrophy and myocardial fibrosis and is capable of up-regulating Nrf2 signaling to promote the expression of its downstream antioxidant proteins SOD1 and HO-1 to reduce the level of ROS.

Effect of miR-124a on collagen-induced arthritis in mice and the underlying mechanisms / 中南大学学报(医学版)

OBJECTIVES@#Rheumatoid arthritis (RA) is a chronic autoimmune disease. MicroRNA has been shown to play an important role in RA. MicroRNA-124a (miR-124a) has anti-proliferative and anti-inflammatory effects in RA fibroblast synovial cells. This study aims to explore the effects of miR-124a overexpression on arthritis in collagen-induced arthritis (CIA) mice and the underlying mechanisms.@*METHODS@#Bovine type II collagen and complete Ferris adjuvant were used to induce CIA model from DBA/1 mice. Twenty-eight days after initial immunization (D28), CIA mice were randomly divided into a model group, a miR-124a treatment group, and a negative control (NC) group. Physiological saline, miR-124a agomir, and miR-124a agomir NC were injected into the skin at the tail root of mice every 3 days for 4 times, respectively. The degree of joint swelling and arthritis index of mice were recorded accordingly. Sixty-three days after initial immunization (D63), the mice were sacrificed to obtain the synovial tissue of ankle joint. HE staining was used to observe the proliferation of synovial cell, infiltration of inflammatory cell, pannus, and bone erosion of synovial tissues; TUNEL staining was used to detect cell apoptosis; qRT-PCR was used to detect the mRNA expression of miR-124a, phosphatidylinositol-3-kinase catalytic subunit alpha (PIK3CA) and its downstream genes Bcl-2 and Bax. Immunohistochemistry was used to detect the protein expression of PIK3CA, Bcl-2, and Bax protein in synovial tissues of each group.@*RESULTS@#Different degrees of swelling presented in the paws of DBA/1 mice at D28, which indicated the CIA model was constructed successfully. Forty-eight days after initial immunization (D48), the paws of mice in the miR-124a treatment group were only slightly red and swollen, while the paws of mice in the model group and the NC group were obviously red and swollen. The arthritis index of mice in the miR-124a treatment group were decreased significantly compared to the NC group at D51, D53, D59, and D62 (51, 53, 59, 62 days after initial immunization) (all P<0.05). Sixty-three days after initial immunization (D63), HE staining indicated that the scores of synovial cell proliferation, inflammatory cell infiltration, synovial pannus, and bone erosion were significantly reduced in the miR-124a treatment group (P<0.05 or P<0.01), while cell apoptosis was increased in the miR-124a treatment group compared with the model group and NC group (P<0.01 or P<0.001). Besides, the expression of miR-124a and Bax in the synovial tissue in miR-124a treatment group was significantly higher than those in the model group and NC group (P<0.01 or P<0.001), while the expressions of PIK3CA and Bcl-2 were decreased (P<0.05 or P<0.01 or P<0.001), and the ratio of Bcl-2 to Bax was significantly decreased (P<0.01 or P<0.001).@*CONCLUSIONS@#Overexpression of miR-124a can reduce arthritis in CIA mice bacause it could promote synovial cell apoptosis and inhibit synovial cell proliferation via targeting PIK3CA and regulating its downstream pathways.

Clinical analysis of elderly patients with anti-MDA5 antibody-positive dermatomyositis / 中华老年医学杂志

Objective:To retrospectively analyze the clinical characteristics of elderly patients with anti-MDA5 antibody-positive dermatomyositis.Methods:Data of 62 patients with anti-MDA5 antibody-positive dermatomyositis admitted to Second Xiangya Hospital from May 2016 to December 2019 were collected and patients were divided into an elderly group(≥60 years old, 17 cases)and a non-elderly group(<60 years old, 45 cases). The clinical manifestations, laboratory test resuls, treatment and prognosis of the patients in both groups were statistically analyzed.Results:A total of 62 patients with anti-MDA5 antibody-positive dermatomyositis were included in this study, including 17 elderly patients(27.4%)with an average age of(65.5±5.3)years and 45 non-elderly patients(72.6%)with an average age of(46.5±8.4)years.Compared with non-elderly patients, older patients had a shorter disease duration[(1.6±1.0)months vs.(3.7±3.3)months, t=3.883, P<0.001], a higher proportion of patients with exertional dyspnea(15/17 or 88.2% vs.26/45 or 57.8%, χ2=5.11, P=0.024)and with combined positive anti-Ro-52 antibodies(15/17 or 88.2% vs.26/45 or 57.8%, χ2=5.11, P=0.024), and a higher mortality rate[(12/17 or 70.6%) vs.(8/45 or 17.8%, χ2=15.748, P<0.001)]. In contrast, fewer elderly patients than non-elderly patients had the Heliotrope's sign(9/17 or 41.2% vs.38/45 or 57.8%), χ2=5.07, P=0.024). Conclusions:Elderly patients with anti-MDA5 antibody-positive dermatomyositis have a unique clinical phenotype with an acute onset, atypical rashes, severe pulmonary lesions, making treatment difficult, and have a poor prognosis.

Analysis of clinical characteristics of elderly patients with rheumatoid arthritis and lung cancer / 中华老年医学杂志

Objective:To investigate the clinical features of elderly rheumatoid arthritis(RA)patients with lung cancer, and to improve clinicians' understanding of this condition.Methods:Retrospective analysis was conducted over general information, clinical manifestations, laboratory results, pathological types, clinical stages, treatment and prognosis in elderly inpatients(≥60 years old)diagnosed with RA and lung cancer admitted to the Second Xiangya Hospital, Central South University from January 2012 to December 2019.Differences between male and female patients were compared.Results:There were 12 elderly patients with RA combined with lung cancer, including 7 males and 5 females, with an average age of(65.8±5.7)years(60-78). The median years from the diagnosis of RA to lung cancer was 11(7.5, 17.3). Eleven patients had clinical symptoms before the diagnosis of lung cancer, with cough and sputum as the most common initial manifestations(9/11). The proportion of smokers in male patients was 71.4%(5/6). Most patients(11/12)had elevated erythrocyte sedimentation rates(ESR)and C-reactive protein(CRP). Eight patients underwent rheumatoid factor(RF-IgM, IgA, IgG)and anti-cyclic citrullinated peptide(ACPA)examinations, and the positive rate was 100% for RF and 87.5% for ACPA.Among 10 patients undergone tumor marker examination, 6 had elevated CEA, 4 had elevated CYFRA21-1, 2 had SCC, 2 had NSE, and 2 had elevated CA125.Among the 12 patients, 7 had adenocarcinoma, 2 had squamous cell carcinoma, 2 had small cell lung cancer, and 1 had carcinoma in situ.Except for 1 case of carcinoma in situ, the remaining 11 patients were all at stage Ⅲ or Ⅳ at the time of diagnosis.Three patients gave up anti-cancer treatment, while the remaining 9 patients received different therapies.In the end, 10 patients died and 2 patients survived so far.The average follow-up time was 17.5(5, 25)months.Further analysis showed that there was no significant difference in clinical manifestations, laboratory test results, pathological types, treatment and prognosis between male and female patients, except that the ESR level was higher in the female group than in the male group(Z=-2.589, P=0.010). However, the average age of male patients was older than that of female patients(68±6.2, 62.6±3.1), and the age of male patients at the diagnosis of RA was also older (56.4±3.8, 52.0±9.5). The proportion of smokers in male patients was significantly higher than in female patients(71.4%, 20.0%), while women had higher proportions than men with elevated CEA(75%, 50%)and NSE(50%, 0.0%). The proportion of women with adenocarcinoma was slightly higher than that of men(80.0%, 42.9%), while the proportions of men with squamous cell carcinoma(28.6%, 0.0%)and small cell carcinoma(28.6%, 0.0%)were slightly higher than those of women.Male patients had a higher mortality rate(100.0%, 60.0%)and a shorter median follow-up time[16.0(2.0, 18.0), 26.0(11.5, 50.0)monthes]. Conclusions:Elderly RA patients with lung cancer are more common in men, and the average age is older than that of female patients.The occurrence of lung cancer is more likely in RA patients with longer disease duration.Most patients are positive with RF and ACPA.Adenocarcinoma is the most common pathological type of lung cancer, and most patients are at clinical stages Ⅲ and Ⅳ.Mortality is high and prognosis is poor.Thus, for elderly RA patients, it is necessary to receive regular monitoring in changes in pulmonary imaging for early detection of lung cancer and improved prognosis.

The short-term efficacy and safety of HA280 immunoadsorption column in patients with idiopathic inflammatory myopathies / 中华风湿病学杂志

Objective:To evaluate the short-term efficacy and safety of HA280 immunoadsorption (IA) column in idiopathic inflammatory myopathies (IIM).Methods:The clinical data of 72 patients with IIM admitted to the Department of Rheumatology of Xiangya No.2 Hospital of Central South University from January 2015 to March 2018 were analyzed. Of these patients, 22 patients were treated with HA280 immunoadsorption column for three times (the immunoadsorption group) and 50 patients were treated with drugs only (the control group). The changes of clinical symptoms and signs, autoimmune antibodies, myocardial enzyme spectrum, the inflammatory markers [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and ferritin], immunoglobulin, complement, other biochemical indexes and pulmonary images of the patients were detected and analyzed before and after the treatment. And then the data were analyzed by Chi-square test, samples t testand Wilcoxon rank sum test. Results:Compared with the control group, the symptoms and signs were obviously improved after treatment with HA280 immunoadsorption column. In particular, the clinical improvement rate of non-specific myositis (89%, 16/18) was higher than that of the control group [(58%, 22/38), χ2=5.379, P<0.05]. And the clearance of autoantibody (control group) was grade 39.41 in average, 28.38 in average in the immunoadsorption group( Z=-2.51, P=0.01), myocardial enzyme spectrum [control 717(1 564) U/L, immunoadsorption group 126(432) U/L , Z=3.09, P<0.01], the inflammatory markers such as ESR [the control group was 24(22) mm/1 h, the immunoadsorption group was 10(7) mm/1 h, Z=-3.0, P=0.003] and immunoglobulin G [the control group was 11(5) g/L, the immunoadsorption group was 9(2) g/L, Z=-4.8, P=0.001] and immunoglobulin M [the control group was 0.9(0.4) g/L, the immunoadsorption group was 1.2(0.8) g/L, Z=-2.0, P=0.05]. Moreover, the lung CT scan showed that pulmonary lesions of the patients in the immunoadsorption group (89%, 17/19) was much more improved than the control group [(61%, 27/44), χ2=4.98, P<0.05]. No serious adverse reactions occurred. Conclusion:HA280 immunoadsorption therapy can significantly clear the autoantibodies, decrease muscle enzymes, inflammatory markers and immunoglobulin, improve lung images of some patients in a short time. It has been shown that it is safein patients with IIM. HA280 immunoadsorption therapy could be an effective treatment for IIM.

Effects of curcumin on endoplasmic reticulum stress PERK-CHOP signaling pathway in pancreas of type 2 diabetic rats / 国际中医中药杂志

Objective:To investigate the hypoglycemic effect of curcumin on type 2 diabetic rats and its effect on the signaling pathway of endoplasmic reticulum stress RNA-dependent protein kinase like-CCAAT/enhancer binding protein homologous protein (PERK-CHOP).Methods:A total of 45 male SD rats were randomly divided into normal control group, model group and curcumin treatment group, with 15 rats in each group. The rats were given high-fat as well as high-sugar diet and intraperitoneally injected with streptozotocin (35 mg/kg, twice, once/day) to establish type 2 diabetes rat model. After the successful establishment of the model, the rats in the curcumin treatment group were given intragastrically with 200 mg/kg curcumin for 30 days. Serum adiponectin level was detected by ELISA, glucose was detected by glucose oxidase, Western blot was used to detect the expressions of PERK, p-PERK, CHOP and ATF4 protein levels in the pancreatic tissues of rats in each group, and mRNA expressions of PERK and CHOP in the pancreatic tissues of rat in each group were detected by real-time PCR.Results:Compared to the model group, the level of blood glucose (14.86 ± 2.77 mmol/L vs. 30.04 ± 3.25 mmol/L) in the curcumin treatment group significantly decreased, and the serum adiponectin level (94.12 ± 16.34 mg/L vs. 53.91 ± 9.08 mg/L) significantly increased ( P<0.05). The expressions of PERK mRNA (0.85 ± 0.07 vs. 1.64 ± 0.28), CHOP mRNA (0.53 ± 0.04 vs. 1.18 ± 0.33), PERK (1.12 ± 0.31 vs. 2.24 ± 0.43), P-PERK (1.23 ± 0.19 vs. 3.89 ± 0.32), CHOP (0.65 ± 0.07 vs. 0.92 ± 0.11) and ATF4 (0.73 ± 0.26 vs. 1.15 ± 0.31) in the curcumin treatment group significantly decreased ( P<0.05). Conclusions:Curcumin has hypoglycemic effect on type 2 diabetes rats, which can enhance the sensitivity of target tissues to insulin by increasing adiponectin levels. Curcumin can down-regulate the expression of PERK/P-PERK/CHOP/ATF4 protein levels in endoplasmic reticulum stress signal pathway, and reduce stress degree.

Correlations of Methylenetetrahydrofolate Reductase Gene Polymorphism and Genomic DNA Hypomethylation Level with Ankylosing Spondylitis / 中国医学科学院学报

To investigate the relationship of both DNA methylation level and methylenetrahydrofolate reductase(MTHFR)gene polymorphism with ankylosing spondylitis(AS). Totally 200 Chinese AS patients with HLA-B27(+)and 120 healthy controls were included from Hunan Province.All the cases were diagnosed according to the 1984 modified New York criteria for AS.The DNA methylation was examined by cytosine extension method,while the MTHFR gene C677T polymorphism was analyzed by the polymerase chain reaction(PCR)and restriction fragment length polymorphism(RFLP).The plasma homocysteine(Hcy)level was examined by enzyme-linked immunosorbent assay(ELISA),while the red blood folate level was analyzed by the specific immunoassays. The ratio of the T/T genotype mutation in the AS group was significantly higher than in the control group(17.0% 5.0%;=9.874, =0.002).The plasma homocysteine concentration of AS group was(18.71 ± 2.42)μmol/L,which was significantly higher than that in normal control group [(10.97 ± 2.93)μmol/L](=24.402, <0.001).The plasma Hcy concentration of the T/T genotype [(21.70±1.80)μmol/L] was significantly higher than that of the C/C genotype[(18.31±1.94)μmol/L](=12.088, =0.01)and the C/T genotype [(17.80±2.18)μmol/L](=6.496, =0.01)in the AS group.The DNA methylation level of the T/T genotype in AS group was significantly lower than that in normal control group(=5.655, <0.001)and also significantly lower than those of the C/C genotype(=11.514, <0.001)and the C/T genotype in AS group(=10.287, <0.001). In the Han population in Hunan Province,the C677T polymorphism of the MTHFR gene is associated with the onset of AS.The T/T mutation at position 677 of the MTHFR gene is an important influencing factor for hyperhcyemia in the AS patients.The T/T mutation at position 677 of the MTHFR gene is associated with genomic DNA hypomethylation.Thus,hypomethylation of DNA may be one of the pathogenic mechanisms of AS.

Effect of Modified Simiaosan on Inflammatory Factors and Neuropeptide Substances of Patients with Synovitis of Knee Joint and Damp-heat Obstruction Collateral Syndrome / 中国实验方剂学杂志

Objective::To observe the clinical efficacy of modified Simiaosan on synovitis of knee joint with damp-heat obstruction collateral syndrome and the effect on inflammatory factors and neuropeptide substances in synovial fluid. Method::One hundred and thirty-five patients were randomly divided into control group(67 cases) and observation group(68 cases) by random number table. Patients' intra-articular effusion was drawn out. Triamcinolone acetonide was injected into arthrosis for 2 times, 1 time/week, and aceclofenac sustained-release tablets were given for 4 weeks, 0.2 g/time, 1 time/day. In addition to the therapy of control group, patients in observation group were also given modified Simiaosan for 4 weeks, 1 dose/day. Before and after treatment, pain, swelling of knee joint and were scored, Western Ontario and McMaster University (WOMAC) were adopted for scoring knee score, and damp-heat obstruction syndrome and local signs of knee joint were also assessed. And levels of interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), hypersensitive C-reactive protein (hs-CRP), substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) were detected. Result::After treatment, scores of pain and swelling of knee joint in observation group were lower than those in control group (P<0.01). Scores of WOMAC, the total score, integral of damp-heat obstruction collateral syndrome, knee flexion-extension range score and floating patella test were all lower than those in control group (P<0.01). And levels of IL-1β, IL-6, TNF-α, hs-CRP, SP, CGRP, NPY and VIP were all lower than those in control group (P<0.01). Analyzed by rank sum test, the clinical efficacy in observation group was better than those in control group (Z=2.089, P<0.05). Conclusion::Modified Simiaosan can significantly alleviate pain and swelling symptoms, promote the recovery of knee joint function, and inhibit the expressions of proinflammatory factors and neuropeptides in synovial fluid, with a better clinical efficacy.

Interpretation of clinical practice guideline for anorectal day surgery 2019 edition / 中华胃肠外科杂志

As the rapid development of minimally invasive techniques, anesthesia, and enhanced recovery after surgery (ERAS), anorectal day surgery receiving more and more attention by improving efficiency of medical care while reducing cost and hospitalized infection. However, day surgery also faces the challenge of completing the whole process from patient admission to discharge within 24 hours. Therefore, establishing a reasonable and detailed day surgery process is the cornerstone to guarantee safe medical practice and patients satisfaction. National Clinical Research Center for Geriatric Disorders (Xiangya), together with China Ambulatory Surgery Alliance formulates the clinical practice guideline for anorectal day surgery 2019 edition. Here we make some interpretations of the guidelines on the detailed process of anorectal day surgery, including indication, preoperative examination, preoperative risk evaluation, health education, assessment of day surgery anesthesia and before leaving postanesthesia care unit (PACU), postoperative management, assessment of discharge and follow-up, for the convenience of various medical centers.

Meta Analysis of Risks of Cardiocerebral Vascular Events in Patients with Primary Biliary Cholangitis / 中国医学科学院学报

To systematically evaluate the risks of cardiocerebral vascular events in patients with primary biliary cholangitis(PBC). Methods We carried out a Meta analysis by RevMan 5.3 software to investigate literatureon the risk of cardiocerebral vascular events in patients with PBC and controls. Results Compared with non-PBC controls,PBC patients had significantly higher risk of coronary events(=1.56,=0.0002);however,the risk of cerebrovascular events showed no significant difference between these two groups(=1.01,=0.94).Subgroup analysis demonstrated a significantly lower risk of transient ischemic attack or carotid stenosis in PBC patients(=0.63,=0.03);however,there was no significant difference in the risk of stroke(=1.11,=0.40). Conclusion Patients with PBC have an increased risk of coronary events but may have a lower risk of transient ischemic attack or carotid stenosis.

High Expression of Multidrug Resistance Gene-1 Can Aggravate Resistance to Methotrexate in Rheumatoid Arthritis Patients / 中国医学科学院学报

Objective To explore the role of multidrug resistance gene-1(MDR1)gene in methotrexate(MTX)resistance in patients with rheumatoid arthritis(RA).Methods Fibroblast-like synoviocytes(FLS)from RA patients were infected with recombinant adenovirus Ad-EGFP-MDR1 to obtain MDR1 over-expressed RA FLS.The transcription level of MDR1 gene and the expression level of its coding product P-glycoprotein(P-gp) rotein were detected by real-time PCR and Western blot analysis.The efflux function was verified by rhodamine 123 efflux assay.The resistance to MTX was detected by MTT assay.Results RA FLS were infected with recombinant adenovirus Ad-EGFP-MDR1;72 hours later,the particles size in MDR1 over-expressed RA FLS increased,the cell volume became larger,and the growth rate decreased.The transcription level of MDR1(1.4325±0.3924 0.0650±0.0070;=6.035,=0.004),the expression level of P-gp protein(1.8667±0.2857 0.9367±0.0551;=5.536,=0.005),and the ability of extracellular rhodamine 123(979.43±196.81 1680.06±147.04;=-4.940,=0.008) in MDR1 over-expressed RA FLS were significantly higher than those of negative virus control RA-FLS,and the survival rate of MDR1 over-expressed RA FLS was significantly increased at each concentration of MTX(<0.05).Conclusion The high expression of MDR1 can affect the efflux ability to MTX by up-regulating the expression of P-gp,thus enhancing the drug resistance to MTX in RA FLS.

Meteorological factors and stroke / 国际脑血管病杂志

Many studies indicated meteorological factors may be independent risk factors for the onset of ischemic and hemorrhagic stroke.Meteorological factors may contribute to the onset of stroke by affecting blood pressure and blood composition,or induced infection.

Association of short-term efficacy for infliximab in rheumatoid arthritis with plasma concentration and anti-drug antibody / 中南大学学报(医学版)

To investigate the correlation between peripheral concentration of infliximab (IFX) or anti-IFX antibody titers and short-term therapeutic effect of IFX in patients with active rheumatoid arthritis (RA).
 Methods: Twenty patients with active RA were treated with combination of methotrexate (MTX), leflunomide (LEF) with IFX, and the clinical and laboratory index and the side effects were recorded before and after IFX treatment. Twenty healthy subjects were chosen as a control group.
 Results: After 14-week treatment, patients were categorized into good, moderate or no responders according to EULAR remission criteria. There were no significant differences in peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels among the 3 groups, and there were no significant correlations among ΔDAS28-CRP, peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels.
 Conclusion: Peripheral IFX concentration, anti-IFX antibody titers and TNF-α levels can not be used as reliable predictive index for short-term effect of IFX in active RA.

Discussions on diversity of new drug creation in China / 中草药

It is a long journey to create a new medicine from discovering the lead to market, which deal with various fields and aspects. There are also many ways and entrances or starting points for the creation of a new medicine. In this article, the following aspects including the ways from traditional Chinese materia medica, folk herbal medicine, active components, and structure modification involved in new medicine creation were discussed. Biomimetic syntheses, metabolites, and key technologies to affect the creative medicine were also summarized based on author's experiences. It is expected to be referenced information and inspired for the colleagues.

Clinical effect of tocilizumab on patients with severe active rheumatoid arthritis / 中南大学学报(医学版)

Objective:To evaluate therapeutic effects and adverse reactions of tocilizumab on patients with severe active rheumatoid arthritis (RA).Methods:Twelve patients with severe refractory RA were treated with tocilizumab.The clinical and laboratory indices and the side effects were recorded after treatment.Results:The clinical and laboratory indices and the disease activity score 28 (DAS28) were observed in all patients,which were significantly improved after TCZ therapy (P＜0.05),and no obvious adverse reactions were found.Conclusion:Tocilizumab can effectively relieve the symptoms and improve the conditions of severe active RA.

Association of TNFRSF1B +676 gene polymorphism with the risk of rheumatoid arthritis in Han Chinese population in Hunan / 中南大学学报(医学版)

OBJECTIVE@#To study the association of TNFRSF1B +676 gene (rs1061622) polymorphism with the risk of rheumatoid arthritis (RA ) in Han Chinese population of Hunan.@*METHODS@#A total of 112 patients with RA from Han Chinese population in Hunan were recruited, along with 129 healthy controls. TNFRSF1B +676 (rs1061622) gene polymorphisms were examined by PCR-RFLP. Serum levels of soluble TNFR II were analyzed by ELISA.@*RESULTS@#RA patients displayed a similar TNFRSF1B +676 genotype to controls (GG/TG/TT: 5/62/45 vs 9/56/64, P=0.167), but signifi cant diff erence was found between female RA patients and female controls (GG/TG/TT: 3/49/24 vs 8/28/48, P0.05). RA patients showed a signifi cantly higher level of serum soluble tumor necrosis factor receptor II (sTNFR II) than controls [(7.83±2.61) ng/mL vs (4.32±1.67) ng/mL, P0.05). No association was found between TNFRSF1B+676 gene polymorphism and RA clinical characteristics.@*CONCLUSION@#In Han Chinese population of Hunan province, TNFRSF1B+676 gene polymorphisms are not associated with the genetic risk of RA .

Open, multicenter, phase Ⅳ clinical trial of Shenbei Guchang capsules in treatment of diarrhea type irritable bowel syndrome / 中国中药杂志

To evaluate the safety and effectiveness of Shenbei Guchang capsules in treatment of diarrhea type irritable bowel syndrome (yang deficiency of spleen and kidney) under widely used conditions, an open, multicenter, controlled, phase Ⅳ clinical trial was conducted in the drug clinical trial centers of 16 domestic hospitals. 2 123 patients from June 10, 2011 to November 29, 2012 were enrolled in the trial. Drug clinical trial was approved by Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital Ethics Committee before implementation. Before the start of trial, subjects were selected according to the research scheme and inclusion criteria, then they would step into the 14 d study after signing Informed Consent Form. All subjects were treated according to the research scheme, evaluated the conditions and filled in CFR sheet, to provide the evaluation data and information on safety and efficacy of Shenbei Guchang capsules. Shenbei Guchang capsules were used to treat diarrhea type irritable bowel syndrome in widely used conditions (2 123 cases), and 2 029 cases of them entered FAS set, cure+markedly effective in 1 921 cases, with a comprehensive curative effect rate of 94.68%; 2 010 cases of them entered PPS set, cure+markedly effective in 1 906 cases, with a comprehensive curative effect rate of 94.83%. The primary symptoms of IBS were abdominal pain and diarrhea. After treatment, both abdominal pain and diarrhea were improved, with significant differences (P<0.000 1). There were significant differences in traditional Chinese medicine symptom scores on both post-treatment day 7 and day 14 as compared with the conditions before treatment (P<0.000 1). 35 cases of adverse events occurred during the trial with an incidence of 1.65%, including 12 cases of drug-related adverse events (adverse reaction) with an incidence of 0.57%, mainly manifested as nausea, abdominal distension and dry mouth, most of which would be spontaneously relieved without any measures. No serious adverse events occurred. The commercially available Shenbei Guchang capsules are proved safe and effective for the treatment of diarrhea type irritable bowel syndrome (yang deficiency of spleen and kidney) under widely used conditions (2 123 cases), and can be continued for clinical promotion and application.

Association of TNF-α gene polymorphisms with the risk of rheumatoid arthritis in Han Chinese population from Hunan / 中南大学学报(医学版)

OBJECTIVE@#To investigate the association of TNF-α-308 gene polymorphism with the risk of RA in Hunan's Han Chinese population.
@*METHODS@#A total of 112 patients with RA from Han Chinese population in Hunan were recruited, along with 129 healthy controls. TNF-α-308 (rs1800629) gene polymorphisms were analyzed by PCR-RFLP. Serum levels of TNF-α were detected by ELISA.
@*RESULTS@#TNF-α-308 A allele carrier was 3.6% in RA patients and 10.5% in controls (P=0.004); male RA patients displayed noticeably lower rates of TNF-α-308 A allele than that in the male controls (2.8% vs 15.6%, OR=0.179, P=0.007). Patients containing both HLA-DRB1*04 and TNF-α-308 GG genotype showed a significant increase in risk for RA (OR=6.107), no matter they were male (OR=7.273) or female (OR=5.029). Female RA patients with both HLA-DRB1*04 and TNF-α-308 GG showed earlier disease onset and higher TNF-α level.
@*CONCLUSION@#In Han Chinese population from Hunan, susceptibility of RA was increased in patients with TNF-α-308 G allele, especially in the female carrier of genotypes; TNF-α-308 A allele may play a positive role in reduction of RA risk in males.