Digestive System Injury Induced by Tripterygium wilfordii and How to Reduce Toxicity and Enhance Efficacy： A Review / 中国实验方剂学杂志

Tripterygium wilfordii is widely used in the treatment of immune system disease and has a remarkable curative effect. Triptolide and Tripterygium glycosides are the most commonly used active ingredients in clinical practice， but their treatment window is narrow and there are many side effects. The damage involves the reproductive system， blood system， cardiovascular system， digestive system， etc. Based on clinical observations and literature summaries， the symptoms of adverse reactions mostly occur in the digestive system （liver and gastrointestinal tract）. Relevant scholars have launched a lot of studies of the manifestations of liver injury induced by T. wilfordii and the mechanism of liver injury. The mechanism is mainly related to liver cell apoptosis， induction of oxidative stress， immune injury， excessive autophagy of liver cells， abnormal fatty acid metabolism， and abnormal enzyme metabolism in liver tissues. This article reviewed and summarized relevant literature on gastrointestinal injury caused by T. wilfordii， but there are few studies on the manifestations and mechanisms of adverse reactions， which still need further research by scholars. In addition， this article also summarized the research on how to reduce toxicity and enhance efficacy of prescriptions prepared from T. wilfordii in the digestive system， mainly involving compatibility with western medicines （Methotrexate， Leflunomide， Iguratimod， etc.）， use along or combination with Chinese medicines （single Chinese medicine， Chinese medicine monomers， and Chinese medicine compounds）， acupuncture and moxibustion （electroacupuncture and moxibustion）， dosage form improvement （glycol plastid gel， self-dissolving microneedle， solid lipid nanoparticles， gastric floating sustained-release capsules， etc.）， processing （steaming， stir-frying， radish seed processing， money grass processing， licorice processing， etc.）， and other methods to reduce toxicity. To sum up， this article analyzed the manifestations， mechanisms， and methods of reducing toxicity and enhancing efficacy of T. wilfordii-induced liver injury and gastrointestinal injury by sorting out relevant literature， in order to provide a reference for the clinical application of T. wilfordii and some research ideas for the future in-depth study of T. wilfordii-induced digestive system injury.

Methodological Evaluation of Advantages of Traditional Chinese Medicine Treatment of Sjögren's Syndrome / 中国实验方剂学杂志

Screening and evaluating the diseases responding specifically to traditional Chinese medicine （TCM） will help to highlight the advantages of TCM treatment， and the evaluation method should be standardized with consideration to the unique characteristics of the diseases. The incidence of Sjögren's Syndrome （SS） is increasing year by year， while the pathogenesis of this disease remains unclear. Modern therapies for this disease include biological agents and immunosuppressants， which generally have unsatisfactory efficacy. The TCM treatment of SS focuses on the harmony of the physical and mental health. The Rheumatology Branch of the China Association of Chinese Medicine organizes experts in TCM， Western medicine， and evidence-based medicine to form working groups. Delphi method and bibliometric method were used for analysis， and SS was selected as a disease responding specifically to TCM. Furthermore， the evaluation system was established for this disease， and the consensus regarding this disease was reached after seminar discussion. This paper summarized the whole process of the evaluation of the advantages of TCM treatment of SS. First， because TCM atomization is widely used in clinical practice and enriches TCM administration methods， this therapy is included after other non-drug therapies were taken as characteristic therapies. Second， the evaluation indicators of therapeutic effect should be determined with consideration to international acceptance and the current research status. Third， the expression method should be accurate， standardized， and objective， highlight the natural advantages of TCM， and avoid arbitrary extension. This paper provides a reference for clinicians to explore other diseases responding specifically to TCM.

Molecular mechanism of ovarian toxicity of Hook.F. a study based on network pharmacology and molecular docking / 浙江大学学报·医学版

To explore the mechanism of ovarian toxicity of Hook. F. (TwHF) by network pharmacology and molecular docking. The candidate toxic compounds and targets of TwHF were collected by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Comparative Toxicogenomics Database (CTD). Then, the potential ovarian toxic targets were obtained from CTD, and the target genes of ovarian toxicity of TwHF were analyzed using the STRING database. The protein-protein interaction (PPI) network was established by Cytoscape and analyzed by the cytoHubba plug-in to identify hub genes. Additionally, the target genes of ovarian toxicity of TwHF were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses by using the R software. Finally, Discovery Studio software was used for molecular docking verification of the core toxic compounds and the hub genes. Nine candidate toxic compounds of TwHF and 56 potential ovarian toxic targets were identified in this study. Further network analysis showed that the core ovarian toxic compounds of TwHF were triptolide, kaempferol and tripterine, and the hub ovarian toxic genes included , , , , , , , , and . Besides, the GO and KEGG analysis indicated that TwHF caused ovarian toxicity through oxidative stress, reproductive system development and function, regulation of cell cycle, response to endogenous hormones and exogenous stimuli, apoptosis regulation and aging. The docking studies suggested that 3 core ovarian toxic compounds of TwHF were able to fit in the binding pocket of the 10 hub genes. TwHF may cause ovarian toxicity by acting on 10 hub genes and 140 signaling pathways.

Practice guideline for patients with ankylosing spondylitis/spondyloarthritis / 中华内科杂志

In recent years, the clinical experts consensuses or guidelines of ankylosing spondylitis (AS)/spondyloarthritis (SpA) have been constantly updated, but to better understand and practice, patient self-participation management is one of the key points to improve the level of diagnosis and treatment. Through questionnaire survey of these patients, we screened out the most concerned issues, and established the AS/SpA patient practice guideline working group with multidisciplinary physicians and patients. Fifteen opinions, as the AS/SpA patient practice guidelines, are proposed in accordance with the relevant principles of the "WHO guidelines development manual" , and with the international normative process.

A multicenter study of fracture in patients with rheumatoid arthritis in China / 中华风湿病学杂志

ObjectiveTo examine the clinical features of fractures and related risk factors in patients with rheumatoid arthritis(RA) in China.MethodsSix hundred and eighty-one RA patients were randomly selected from department of rheumatology of 18 hospitals of China.Data were obtained from the questionnaire,including age,sex,disease duration,the involvement of joints,treatment regimen,features of fractures etc.The possible risk factors of fracture in patients with RA were analyzed with a multi-variate Logistic regression analysis.Results① In 681 RA patients of the survey,48 patients had 54 fractures,and the incidence of fractures was about 8％.② Fractures occurred at various sites.Foot/ankle,femur,spine and wrist were the mostfrequent sites.③ The Logistic regression analysis showed that several factors increased the risk of fracture in RA patients,including long disease duration (OR:1.245,95％CI:0.987-1.570,P=0.065),male gender(OR:0.433,95％CI:0.199-0.942,P=0.035),more deformed joints(OR:1.042,95％CI:1.006-1.079,P=0.023),family history of RA (OR:2.201,95％CI:0.984-4.923,P=0.055),and high scores of SF-36(OR:1.017,95％CI:1.002-1.033,P=0.028).④ According to the degree of correlation from strong to weak,the risk factors of fracture were disease duration,SF-36,sex,number of deformed joints and family history of rheumatoid arthritis.ConclusionThe incidence of fracture is high in patients with rheumatoid arthritis.Several factors could increase the risk of fractures in RA patients,including long disease duration,male gender,more deformed joints,and family history of RA.In order to prevent the occurrence of fractures,cautions should be taken to prevent the development of fractures and treat the disease aggressively to suppress the disease activity of RA.

ReABLE study on the efficacy and long-term safety of recombinant human tumor necrosis factor-α receptor Ⅱ IgG Fc fusion protein with methotrexate in active rheumatoid arthritis / 中华风湿病学杂志

ObjectiveTo evaluate the clinical and radiographic efficacy and safety of the combination of recombinant human tumor necrosis factor-αt receptor Ⅱ IgG Fc fusion protein (rhTNFR:Fc) and methotrexate (MTX) in patients with rheumatoid arthritis (RA). MethodsThirty patients with highly active RA were treated with rhTNFR:Fc (25 mg subcutaneously twice weekly) and oral MTX (up to 15 mg weekly). Clinical efficacy was assessed using ACR response criteria and the disease activity score in 28 joints (DAS28).Radiographs of the hands and wrists were assessed with the modified Sharp score. Chi-square test, Fisher is exact test and paired t-test were performed. ResultsAt week 52, ACR20, ACR50 and ACR70 responses were achieved by 90％, 87％ and 67％ respectively. At week 52, mean DAS28 was 3.4±1.1 compared to 6.4±0.6 at base-line(P＜0.01), with 23％ patients achieving clinical remission and 17％ patients in low disease activity. Similarly, the HAQ was improved significantly, declining from 1.18±0.56 at base-line to 0.25t±0.34 at week 52 (P＜0.01). No radiographic progression was found in 22 cases. Adverse events were mild in general.ConclusionTreatment with rhTNFR:Fc plus MTX has shown good efficacy throughout 52 study period in reducing disease activity, improving function, and retarding radiographic progression. Combination therapy for 52 weeks can achieve disease remission and no radiographic progression, which are the two goals of therapy for RA.

A multicenter study of costs of drugs in rheumatoid arthritis in China / 中华风湿病学杂志

Objective To describe the distribution of medication costs of rheumatoid arthritis patients, and to analyze the factors that may affect the costs. Methods Data were obtained from a 12-month retrospective investigation of patients with rheumatoid arthritis (RA) across China. Department of Rheuma-tology of 18 hospitals were randomly selected. The data about their social conditions, clinical conditions, medications associated with RA such as disease-modifying antirheumatic drugs (DMARDs), non -steroidal anti -inflammtory drugs (NSAIDs), steroids, biologic agents were collected, and the costs of drugs were calculated. A non-parameter test and multivariate logistic regression analysis were performed. Results Six hundred and forty six patients were enrolled into the study, 435 completed data were chosen for analysis. The results demonstrated that the average costs per patient for medications in the past year was 8018 . The total medication costs were further subdivided into the following parts: DMARDs, (represented 20% of the total costs), biologic drugs (49%), NSAIDs (4%), herbal drugs (22%), steroids (1%). Data analysis showed that patients with higher education and higher incomes, with medical insurance,better health function status and outpatients paid more on DMARDs. Extra-articular manifestations increased the odds of the high-cost group (OR: 2.180, 95%CI: 1.335～3.558, P=0.002), while poor health function status increased the probability of paying high costs (OR: 1.373, 95%CI: 1.012～1.863, P=0.041). Conclusion High medication costs in RA do exist in RA patients. The costs of medication is associated with health function status and the presence of extra-articular manifestations.

Effects of Bushen Huoxue Fang on estrogen receptor alpha mRNA in pituitary body of ovariectomized rats with collagen-induced arthritis / 中国组织工程研究

BACKGROUND: Pharmacological researches demonstrate that Chinese crude drugs of invigorating the kidney contain flavonoids such as prepared rhizome of rehmannia and kudzuvine root, they possess phytoestrogenic effect, among them, isoflavone acts as a regulator of estrogen receptor.OBJECTIVE: To approach the effects of self-planned Bushen Huoxue Fang (BSHXF) on the serum estradiol and estrogen receptor α mRNA expression in pituitary gland in rats with collagen-induced arthritis. DESIGN, TIME AND SETTING: Randomized grouping controlled animal experiment was performed in the central laboratory of Bethune Intemational Peace Hospital of Chinese PLA between May 2006 and May 2008. MATERIALS: Sixty female and healthy Wistar rats were randomly divided into sham operated group (n=10) and operation group (n=50). Operation group was reproduced collagen-induced arthritis model at 2 weeks following ovariectomy. The rats of arthritic index ≥ 5 were assigned into model group, BSHXF group, methotrexate (MTX) group, and MTX + BSHXF group, each group included 10 rats. The Chinese crude drugs were bought from LERENTANG drugstore in Shijiazhuang, including rhizoma drynariae, safflower, prepared rhizome of rehmannia, Herba Epimedii, danshen root, kudzuvine root and so on. After routine decoction, centrifugalization, rogue and condensing 1.3 kg/L decoction, the solution was sealed up, divided pack and reserved at 4℃.METHODS: Sham operated group and model group were intragastrically administered with normal saline 2 mL per day; BSHXF group with BSHXF decoction 2 mL per day; MTX group with MTX 2.6 mg/kg (2 mL) once a week, and normal saline 2 mL per day at other time points; MTX + BSHXF group with MTX 2.6 mg/kg (2 mL) once a week and BSHXF juice 2 mL per day. Each group was given 6 weeks.MAIN OUTCOME MEASURES: After blooding by abdominalis aorta, magnetic-split enzyme linked immunosorbent assay was applied to detect the level of serum estradiol. Reverse transcription-polymerase chain reaction detected the expression of estrogen receptor a mRNA in rat pituitary gland.RESULTS: Compared with model group, the expression of estrogen receptor a mRNA in pituitary gland increased in the MTX group, but there was not statistically significant. BSHXF + MTX group showed a significantly increased expression (P < 0.01). The expression of estrogen receptor α mRNA in BSHXF group was higher than MTX group, but lower than BSHXF + MTX group (P < 0.05). No significant difference existed between BSHXF group, BSHXF + MTX group and sham operation group. Compared with sham operation group, there were statistically significant decrease of estradiol in the model group. Compared with model group, the estradiol levels were shown to increase in three treatment groups. Among them, MTX group had slightly slower level with no significant difference (P > 0.05), while BSHXF + MTX group had the most obvious increase, which was close to normal level (P < 0.01). There was a significantly positive correlation between estradiol and the expression of estrogen receptor o mRNA (r=0.483, P < 0.05).CONCLUSION: Serf-planned BSHXF possessing oestrogenic hormonelike role can elevate the level of serum estradiol and upregulate the expression of estrogen receptor a mRNA in pituitary gland.

Correlations between serum macrophage migration inhibitory factor and active rheumatoid arthritis / 中国组织工程研究

BACKGROUND: Macrophage migration inhibitory factor (MIF) is mainly concerned with macrophage mobilizing function, as the upper stream cytokine of tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β), which may have critical effect in the process of the onset of rheumatoid arthritis. OBJECTIVE: To explore the correlations between the change of serum MIF and the activity of rheumatoid arthritis (RA) disease.DESIGN, TIME AND SETTING: Non-randomized control and case study, which was carried out in the Bethune International Peace Hospital of Chinese PLA from September in 2005 to October in 2006.PARTICIPANTS: Sixty RA patients were included in this study, and other thirty healthy subjects were selected as the control group. There were significant differences in age and sex between the two groups. METHODS: Clinical data of sixty RA patients were selected by carrying out retrospective analysis, then on the basis of disease activity score (DAS) accumulated points, they were divided into active and inactive group respectively, who were contrasted with 30 health adults. MAIN OUTCOME MEASURES: ① Morning stiffness (in minutes), joint tenderness index, arthrocele index, semi-quantity rheumatoid factor (RF), C-reactive protein concentration (CRP), erythrocyte sedimentation rate (ESR), and platelet count (PLT) were recorded; ② To compare the level of serum MIF, IL-1β and TNF-α among active group, inactive group, and control group; ③ The correlation analysis was carried out among the level of serum MIF, inflammatory index and clinical observation index.RESULTS: There was significantly increased in serum MIF of patients in the active group compared to of inactive and normal groups (P < 0.05), but there were no significantly differences between inactive and control groups (P > 0.05). There were significant correlations between the serum MIF concentration and active inflammatory index of RA disease, blood sedimentationrate (ESR), C-reactive protein (CRP), platelet counting (PLT), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), swell joint index (SJI) and tenderness joint, but no significant difference was observed between the serum MIF, age, disease course, morning stiffness and rheumatoid factor (RF).CONCLUSION: The serum MIF concentration is significantly increased in patients with RA, and it may be a useful parameter for monitoring disease activity of RA.

An animal model of alcoholic fatty liver and the prevention and treatment with New Qinggan Decoction / 中西医结合学报

OBJECTIVE: To establish an animal model of alcoholic fatty liver (AFL) and to observe the prevention and treatment with New Qinggan Decoction (NQGD). METHODS: Female SD rats were exposed to the mixture of white spirit and corn oil continuously for up to 6 weeks via an intragastric feeding protocol. The pathologic alteration of the liver and the changes of serum lipid were observed, and the effect of NQGD for preventing and treating AFL was studied. RESULTS: Wide hepatic steatosis was induced in model group rats. Serum triglyceride (TG) and total cholesterol (TC) of the model group were higher than those of the normal group (P<0.01). Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of the model group were higher than those of the normal group (P<0.05). In NQGD group, hepatic steatosis was milder than that in the model group, and serum TG, TC, AST, ALT descended significantly as compared with the model group (P<0.01). CONCLUSION: AFL model of rats established by feeding the mixture of white spirit and corn oil is similar to the episode of the human AFL, and is easy to intervene with medicine. NQGD can prevent the occurrence of AFL in this model.

Toxicity-reducing and Action-enhancing Effects of Total Glucosides of Paeony on Tripterygium Glycosides in Treating Lupus Nephritis / 中药新药与临床药理

Objective To investigate the toxicity-reducing and action-enhancing effects of total glucosides of paeony (TGP) on tripterygium glycosides (TG) in treating murine lupus nephritis (LN).Methods Chronic graft-versus-host disease (cGVHD) murine LN model was established.Modeling mice were randomly divided into three groups:LN group,TG group (in the dose of 30 mg?kg-1?d-1),and TG+TGP group (TG in the dose of 30 mg?kg-1?d-1 and TGP in the dose of 200 mg?kg-1?d-1),6 mice in each group.Another six normal mice served as control.Medication groups received corresponding medicine according to the experimental design,and mice in the normal control group and LN group received the same volume of saline,qd,for 4 weeks.After the treatment,the levels of 24-hour urinary protein excretion (UPE),blood urea nitrogen (BUN),serum creatinine (SCr),serum alanine transferase (ALT) and aspartate transferase (AST),and contents of superoxide dismustase (SOD),malondialdehyde (MDA),and glutathione peroxidase (GSH-Px) in liver tissue homogenate were measured.Meanwhile,the pathologic changes of kidneys in each group were detected.Results Compared with LN group,levels of UPE,BUN and SCr in TG group and TG+TGP group were decreased notablely (P

Cationic liposomes complexed to plasmids encoding endostatin and angiostatin inhibit lewis lung cancer in mice model / 肿瘤研究与临床

Objective To evaluate the inhibitory effect of cationic Liposomes complexed to plasmids encoding endostatin and/or angiostatin on the growth and metastasis of Lewis lung cancer in mice model. Methods C57BL/6j mice were established as mice model. Cationic liposome complexed plasmids encoding angiostatin and endostatin were administrated intratumorally to inhibit the growth and metastasis of the implanted tumor. The size change of the tumor; metastasis in lung, the activity, nourishment, survival period of the mice were observed to evaluate the function of cationic liposome complexed plasmids. Results The treatment group could inhibit the growth and metastasis of the implanted tumor. Comparing with control group, they showed significance in tumor size, metastasis in lung and survival period of the mice (P

Effects of prevention and treatment on atrophic gastritis in rats with Zengshengxiao Capsules / 中成药

Objective:To study the protective and therapeutic effects of Zengshengxiao Capsules (ZSX) on atrophic gastritis in rats. Methods: The model was established by methods of active immunity and gastrogavage with bile and hot water. The method of acetic acid writhing was used. Results: (ZSX) had actions of promoting the blood flow of gastric mucosa, increasing in pH, inhibiting inflammatory cell infiltration, glandular atrophia and atypical hyperplasia. It also had action of alleviating pain. There were no toxic and side effects. Conclusion: (ZSX) had remarkably preventive and therapeutic effects on atrophic gastritis of rats.