Extremely severe pancytopenia induced by low dosage of azathioprine in systemic lupus erythematosus patients is rare. A 40-year-old Chinese female was diagnosed with systemic lupus erythematosus. She suffered worse erythema, oral ulceration, raised erythrocyte sedimentation rate and high anti-dsDNA in August 2013. Then she was initiated on oral azathioprine 50mg/d and extremely severe pancytopenia was seen in September 2013. She was recovered by a series of treatments. Regular monitoring of blood counts is highly recommended to reduce the possible serious myelosuppression induced by azathioprine.

OBJECTIVE:To explore the development status of regulatory policies of biosimilars in foreign countries,and to provide reference for perfecting biosimilars regulatory policies in China. METHODS:Comparative analysis was conducted,con-cerning biosimilar regulations and directories which had been issued by WHO,EMA and FDA,in aspects of biosimilars definition, the choice of reference drug,quality studies,non-clinical studies,clinical studies. RESULTS & CONCLUSIONS:Three common points found in foreign regulatory policies were that:firstly,discrepancies were allowed between biosimilars and reference drugs;secondly,the comparison was itemized between biosimilars and reference drugs on safety and effectiveness,in order to guarantee the reliability of quality research;thirdly,clinical and non-clinical studies were reduced with a premise that similarity is confirmed. Given China's current situation,several parts of policies should be improved,including stressing pertinence of reference drug selec-tion,refining preclinical and clinical study directories and establishing supporting system after listing.

Total 150 patients with chronic pelvic pain syndrome were randomly divided into three groups with 50 cases in each group. Patients were treated with tamsulosin, Qianlie'an Shuan and tamsulosin plus Qianlie'an Shuan for 12 weeks, respectively. Patients were assessed with the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) before and after treatment. The score of NIH-CPSI decreased from 25. 1 ± 2. 2 to 19. 5 ± 1.7 after treatment in tamsulosin group; 25.0 ± 2. 2 to 19. 1 ± 1.7 in Qianlie'an Shuan group, and 24. 8 ± 1.7 to 16. 8 ± 1.4 in combined therapy group, all P ＜0. 01. The results indicated that tamsulosin, Qianlie' an Shuan or combined therapy were all effective in alleviating the symptoms and improving the quality of life, and the combined therapy was superior to single therapy in relief of symptoms.

The status of anesthesia and psychotropic substances use for cancer pain control was analyzed in 355 cancer patients in Huanggu District of Shenyang City.The results revealed that patients aged 60 and above accounted for 62.8％ of the total; the 5 leading diseases were lung cancer ( 132 cases,37.2％ ),colorectal cancer (34 cases,9.6％ ),liver cancer (33 cases,9.3％ ),stomach cancer ( 31cases,8.7％ ) and pancreatic cancer (20 cases,5.6％ ).There was no significant difference in constituent ratio of disease categories in the last 4 years ( x2 =18.75,P ＞ 0.05 ).The daily oral dose of morphine sulphate was 60 - 200 mg with an effective rate of 91.5％ (325/355). The side effects including constipation,nausea,vomiting and itching can be effectively reduced by prophylactic medication.

OBJECTIVETo explore the effect of Danlou Tablet (DT) on arrhythmia model rats induced by transient myocardial ischemia/reperfusion (I/R).

METHODSTotally 45 healthy Wistar rats were randomly divided into 3 groups, the sham-operation group, the model group, and the DT group, 15 in each group. Rats in the sham-operation group and the model group were administered with distilled water by gastrogavage at the daily dose of 0.1 mL/kg. Rats in the DT group was administered with 0.53 g/mL DT suspension by gastrogavage at the daily dose of 0.1 mL/kg. All medication was lasted for 10 successive days. The myocardial I/R experiment was performed at 1 h after the last gastrogavage. ECG was performed before ligation and at I/R. The jugular arterial blood pressure of all rats was measured during the whole course. ST segment changes were observed at each time point of I/R. The ventricular fibrillation, the premature ventricular, the number and the duration of ventricular tachycardia within 30 min reperfusion were also observed. Activities of Na(+)-K+ ATPase and Ca2+ ATPase in the myocardium homogenate were detected as well.

RESULTSThe jugular arterial blood pressure and the heart rate were slightly lower in the DT group than in the model group, but with no statistical difference (P > 0.05). Compared with the sham-operation group, the degree of ST segment was obviously elevated in the model group at 0, 5, and 7 min (P < 0.05). It was significantly lower in the DT group than in the model group (P < 0.01). ST seg ment was more elevated at 5 min than at 0 min in the model group, but the degree of ST segment elevation was still obviously lower in the DT group than in the model group (P < 0.05). There was no statistical difference in the degree of ST segment elevation at 7 min between the two groups (P > 0.05). At 0 min when the decrement of ST segment exceeded one half the ischemia, there was no statistical difference in the degree of myocardial ischemia between the model group and the DT group (P > 0.05). Compared with the model group, the incidence of fatal and nonfatal ventricular fibrillation, the frequency and duration of ventricular tachycardia and premature ventricular beats were obviously lessened, and activities of Na(+)-K+ ATPase and Ca(2+)-ATPase increased (all P < 0.05).

CONCLUSIONSDT could significantly protect arrhythmias induced by transient I/R. Its effect might be related to lowering the degree of myocardial ischemia, and increasing ion transport channel related enzyme activities.

Animals ; Arrhythmias, Cardiac ; drug therapy ; etiology ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Male ; Myocardial Reperfusion Injury ; complications ; Rats ; Rats, Wistar

Objective　To investigate the changes of free calcium distribution in hepatocytes after administration of phenylephedrine. Methods The changes of fluorescence intensity were observed by confocal laser scanning microscopy after administration of phenylephedrine alone or pretreated with phentolamine before phenylephedrine administration. Results　The fluorescence intensity increased rapidly after administration of phenylephedrine to hepatocytes. When liver cells were pretreated by phentolamine before phenylephedrine administration, the changes of fluorescence intensity not obvious. Meanwhile, the inconformity of the fluorescence intensity in hepatocytes suggested the existence of the second subarea of free calcium distribution. Conclusion　Ca2+ signal can be arisen by phenylephedrine via the α-receptor in hepatocytes in vitro. The distribution and dynamic changes of free calcium in hepatocytes display some characteristics.

Objective To explore the risk factors of newly emerging advanced schistosomiasis patients in endemic areas.Methods The study areas were selected in two counties of Dongting Lake regions and a 1 :2 match case-control study was designed.Sixty schistosomiasis patients,who newly evolved into advanced schistosomiasis from 2006 to 2007,were selected into the case group,and 120 cases with chronic schistosomiasis into the control group.Questionnaires including potential risk factors of advanced schistosomiasis were designed and the information was collected based on face to face interviews.SPSS 12.0 was used to analyze the simple factors and multi ones (logistic regression) attributable to the development of advanced schistosomiasis.Results The history of hepatitis B (OR = 10.729),models of water contact (OR = 3.919) ,yearly exposure days to the infested water (OR = 5.457) and times of chemotherapy in the nearly 10 years(OR = 1.578) were the risk factors of development of advanced schistosomiasis.The times of examinations with positive schistosome eggs were protective factors.No association was found between yearly income,education degree,times of checking for schistosomiasis,times of examination with sera positive results and the emergence of advanced schistosomiasis.Conclusion The high frequency of exposure to the infested water,repeated infections,incomplete diagnosis and treatment are the risk factors of advanced schistosomiasis.The concurrent infection with hepatitis B is associated with the acceleration of development of advanced schistosomiasis.

Objective To investigate the effects of 4-aminosalicylic acid (4-ASA) on rats with 2,4,6-trinitrobenzenesulfonic acid-induced colitis in order to understand its mechanisms in treatment of inflammatory bowel disease (IBD). Methods Thirty SD rats were given 2,4,6-trinitrobenzenesulfonic acid to induce colitis and were divided into model group, 5-ASA (200 mg/kg) treated group and 4-ASA (200 mg/kg) treated group with 10 each. Another 10 rats were severed as normal control. Seven days later,all animals were sacraficed for estimation of colonic tissues. The iNOS and serum level of interleukin (IL)-8 were detected by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) ,respectively. And the apoptosis of polymorphonuclear neutrophil (PMN) was examined by flow cytometry. Results In comparison with model group, the body weight was increased in rats treated with 4-ASA (t= 14.09,P<0.01), whereas the macroscopic and histological scores and MPO activity were decreased (t=7.87,18.37,6.66 and 19.60,respectively, all P values <0.01), which were similar to 5-ASA treated group (all P values > 0. 05). The expression of tissue iNOS was 73.55%±5.15% in model group, which was higher than that in control group [(5.95±1.45)% ,t=39.93,P<0.01)],but was lower than that in 5-ASA treated group [(37.80±3.82)%,t = 17.62,P<0.01] and 4-ASA treated group [(42.27±3.52) %, t= 15.76 ,P<0.01]. The serum level of IL-8 in model group was significantly higher than that in 5-ASA treated group and 4-ASA treated group (P<0. 01). The apoptosis of PMN in model group was lower than that in control group (t= 11.48,P<0.01), but higher than that in 5-ASA treated group (t= 7.51, P<0.01) and 4-ASA treated group (t= 10.47,P<0.01). Conclusions The efficacy of 4-ASA in treatment of IBD may be related to the mechanisms of reducing the migration and the activities of PMN, up-regulating PMN apoptosis and scavenging reactive oxygen radicals produced by PMN.

Objective To investigate the effects of Gefarnate on expression of myeloperoxidase (MPO),cyelooxygenase-1 (COX-1) and COX-2 in trinitrobenzene sulphonic acid (TNBS) induced experimental colitis in rats and its therapeutic effects on ulcerative colitis. Methods Forty female Sprague-Dawley (SD) rats were randomly divided into 4 groups with 10 each. The rats in group A, B and C were infused with TNBS/alcohol by enema. After the production of colitis, the rats in group A or B were treated daily with 1 ml of normal saline or with 1 ml of 5-ASA (100 mg/kg) by enema,and those in group C were treated daily with 1 ml of Gefarnate by gavage. Group D was served as normal control. After the production of colitis,animals were sacrificed at day 7 and 14 with 5 in each group. The macroscopic changes of the colon were evaluated according to disease activity index (DAD scoring and histological change was assessed by HE staining. MPO activity of the mucosa was detected by biochemical methods. Expressions of COX-1 and COX-2 in tissues were detected by immunohistochemistry. Results Compared with group A, macroscopic and histological scores and MPO activity were significantly decreased in group B and C (P<0.05). The expressions of COX-1 at day 7 and 14 were 1.86±0.51 and 1.96±0.41 in group B, 1.73±0.68 and 1.79±0.6 in group C, 1.91±0.34 and 1.99±0.45 in group D, respectively, which were significantly higher than those in group A (0.87±0.18 and 0.93±0.15, P<0.05). Whereas the expressions of COX-2 at day 7 and 14 were 1.53±0.19 and 0.73±0.15 in group B, 1.73±0.94 and 0.86±0.29 in group C, 0.24±0.18 and 0.18±0. 16 in group D, respectivley, which were significantly lower that those in group A (3.50±0.2;3 and 3.06±0.27). There was a significant difference between group D and group B or C (P<0.05). Conclusions Gefarnate provides a therapeutic effect during TNBS-induced colitis in rats, which is similar to that of 5-ASA. The mechanisms are involved in decreasing the concentration of colonic MPO and regulating the expression of COX-1/COX-2.

Objective To establish hybridization method by using the DNA-modified colloid gold nanopartieles probes for rapid and specified detection of methicillin resistant Staphylococcus aureus (MRSA). Methods DNA-modified nanoparticles probes were prepared by using two mereapto-modified mecA gene-specific oligonucleotide probes bounding with 6Ohm-diameter colloid gold nanoparticles through covalent binding. Genomic DNA of Staphylococcus aureus strains were extracted and then fragmented by ultrasonic waves. The fragmentized DNA was hybridized with the DNA-modified colloid gold nanoparticles probes. The reaction products were centrifuged and then detected by reversed-phase thinlayer chromatography plate to observe any colloid gold nanoparticles precipitation. The results of mecA gene detected by the colloid gold nanoparticles probes hybridization were compared with the results of PCR and the accuracy of the hybridization method was evaluated. Results Of total 95 tested strains, 71 strains were confirmed as MRSA and 24 swains were confirmed as methicillin susceptible Staphylococcus aureus (MSSA) by PCR. Of 71 MRSA strains, 69 strains were positive by colloid gold nanoparticles probes hybridization, the sensitivity of this method was 97.2%. All of the 24 MSSA strains were negative by using this technique. The specificity of this method was 100%. Of total 95 test strains ,93 strains were detected correctly. The accuracy was 97.9%. Conclusions Colloid gold nanoparticles probes hybridization test is well consistent with the gold standard method of PCR in detection of MRSA. Detection of MRSA by using the technique of the DNA-modified colloid gold nanopartichs probes hybridization is rapid, simple and accurate. It is potent to be a new method for rapid diagnosis of MRSA infection.