Juvenile idiopathic arthritis(JIA)is the most common rheumatology disease in childhood period with poor prognosis.The biological agents are newly developed drugs with features of clear therapeutic targets and fast effects.But its use in JIA is still limited,so this article focuses on the clinical use experience,timming and sideffects of the biological agents on JIA.

Objective To investigate the effects of T. gondii soluble tachyzoite antigen (STAgs) on the survival time of mouse heart allograft and the possible mechanism. Methods The STAgs were prepared by pulverizing T. gondii tachyzoite with ultrasound on ice. Cervical heterotopic heart transplantations were done by using Balb/c mice as donors, and C57BL/6 mice as recipients.The recipients were classified randomly into three groups: syngeneic group, acute rejection group and STAgs-treated group. The recipients in acute rejection group and STAgs-treated group were injected subcutaneously with 0. 1 ml PBS and 0. 1 ml (5 μg) STAgs at the 4th day before transplantation respectively, and those in syngeneic group were not subjected to any treatment. The grafts were observed daily by cervical palpation, and the total cessation of cardiac contraction was defined as the endpoint. The heart allografts were harvested at the 7th day after transplantation for pathological examination and immunohistochemical staining for CD4+ T, CD8+ T. Results The recipients in syngeneic group were all alive at the 100th day after transplantation. The average survival time in acute rejection group and STAgs-treated group was (6.7± 0.5) days and (70.8± 3.5) days,respectively (P＜0.05). HE staining showed that the rejection on the 7th day after transplantation in syngeneic group, acute rejection group and STAgs-treated group was fallen into 0 degree, Ⅲ-Ⅳ degree and 0- Ⅰ degree, respectively. Immunohistochemical staining revealed that the CD4+ T and CD8+T were markedly down-regulated in STAgs-treated group as compared with those in acute rejection group. Conclusion T. gondii STAgs can significantly prolong the survival time of mouse heart allograft and inhibit the rejection probably by changing the ratio of TH1/TH2, or inhibiting the effect of dendritic cells by inducing the lipoxin A4.

In the treatment of hypertensive crisis, the novel Rho kinase inhibitor DL0805-2 can rapidly lower systematic blood pressure, reduce pulmonary artery pressure, and has a significant protective effect on lung injury. This experiment intends to evaluate the efficacy of DL0805-2 against pulmonary arterial hypertension (PAH) and preliminarily reveals its underlying mechanism. Animal welfare and experimental procedures are in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Sprague Dawley (SD) rats were randomly divided into DL0805-2 low, medium, and high dose groups (1, 3, and 10 mg·kg^-1), bosentan positive control group, model group, and blank control group. The drug was administered daily on the 7th day after model establishment by monocrotaline injection. On the 25th day of the experiment, relevant indicators were examined to observe the therapeutic effect of DL0805-2 on pulmonary hypertension. DL0805-2 significantly relieved the abnormal changes in the physiological parameters related to PAH induced by monocrotaline, including reducing right ventricular systolic pressure, alleviating cardiac damage caused by pressure overload, and reducing the levels of endothelin-1 and inflammatory factors in lung tissues. DL0805-2 also attenuated pulmonary arteries remodeling. It was preliminarily discovered that DL0805-2 exerts preventive and therapeutic effect on PAH through Rho-kinase pathway. Our results suggested that DL0805-2 had good therapeutic effects on monocrotaline-induced PAH rat model. It intervened early in the disease process, effectively prevented the development of the disease, and reduced the mortality of the diseased animals. The mechanism is related to Rho-kinase pathway.

OBJECTIVE:To evaluate the availability and equipment of antidiabetic drugs in public hospitals from Shaanxi prov-ince. METHODS:Using a standardized methodology developed by WHO and Health Action International,the availability and equipping rate of the most common oral antidiabitic drugs were investigated and evaluated in public hospitals of Shaanxi province. RESULTS:The availability and equipping rate of tertiary hospitals and secondary hospitals were all higher than those of community health service centers. Among generic drugs,the availability of metformin was the highest (94.4%),and those of glibenclamide and repaglinide were the lowest(5.6%). Among original drugs,the availability of acarbose was the highest(68.1%). The equip-ping rate of original drugs was higher than that of generic drugs. The equipping rate of generic drugs(25.0%)was higher than that of original drugs(12.5%)in community health service center,but the equipping rates of generic drugs and original drugs were in low level. CONCLUSIONS:General hospitals (especially tertiary hospitals) have high equipping rate of original antidiabetic drugs,the community health services have low availability and equipping rate. Comprehensive measures should be taken to im-prove the availability of drugs in primary medical institutions and ensure drug use of chronic disease patients in primary hospitals.

Objective To investigate the developmental feasibility of early human fetal testes (<3 months) using xenografting technique and to acquire an accessible donor derivation that is essential for studying human germ cell development. Methods Nine testes from 10-13 weeks aborted fetus were grafted under the back skin of 6 castrated nude mice. Grafts were collected at different time point according to the growth of the donor tissues and the health condition of the recipients. Morphological and histological analyses were performed for the observation of the development of grafted immature testicular tissues. Results The mass of grafts was increased from about 5-7mg to 84.1mg (the biggest). Six of 9 testes were to be in developing. Histological observations showed a significant expansion of seminiferous tubules from (44.26±3.14)μm to (77.69±7.47)μm. Cells dispersedly distributed in seminiferous cords at the time of grafting migrated towards the basal part of seminiferous epithelium. Some germ cells with spermatogonium-like characteristics located on the basement membrane. Sertoli cells were in stages from immature into matured with abundant cytoplasm which were orderly arranged around spermatogonia forming a niche-like structure. Conclusion Testes from early aborted human fetus grafted under the back skin of castrated nude mice showed further development and therefore could be used as an easier accessible donor tissues for the investigation of human spermatogenetic mechanism.

Objective To elucidate the clinicopathological and hereditary characteristics in Fabry nephropathy.Methods The clinical and pathological features of 14 patients with Fabry nephropathy were collected.The activities of α-Gal A were measured in 4 probands.Screenings of GLA mutations were done in 12 patients.Results The ratio of Fabry nephropathy in the patients with renal biopsy was 0.074 ％ (14/19 005),the average diagnostic age was (30.57±9.32) years,male to female ratio was 2.5∶ 1.All the patients had proteinuria,and the median of urine total protein (UTP)was 1.71 g/24 h (0.32-4.71 g/24 h).Two of them got nephrotic proteinuria,5 of them got microscopic hematuria,4 of them got renal function insufficiency.Angiokeratomas was the most common manifestation (10/14),followed by cardiac involvement (6/14).Hypohidrosis and diseases of central neural system could also be seen in these patients.There were 9 classic phenotype,the remaining 5 were variants/renal variants.The family information was collected in 10 pedigrees,6 of them had family histories of kidney disease.Renal pathology showed vacuolization of glomerular visceral epithelial cells was the prominent feature,global and segmental glomerulosclerosis were seen in some patients by light microscopy.The myelin bodies or zebra bodies were identified in podocytes by electron microscopy,but only were found in some podocytes of 2 females.The activity of α-Gal A was decreased compared with the normal range in 4 probands.The mutations of GLA were demonstrated in 11 patients.Three novel mutations of GLA gene were identified,which were all deletion/insertion mutations with classic phenotypes.Most variants carried the mutations located in the buried/partial buried areas of α-Gal A (3/11).The classical phenotype carried GLA mutations as W162X,F169S,S201F,N272K,L310R,while variant phenotype carried GLA mutations as I91T,R112H,Q312H.Conclusions The ratio of Fabry nephropathy in patients with renal biopsy is 0.074％.Angiokeratomas and cardiac involvement are often accompanied with Fabry nephropathy.The genotypes of GLA may have close relationships with the phenotypes of Fabry nephopathy.

Objective To investigate the prottective effect of ulinstatin on lung of rats with sepsis and its mechanism of ameliorating cell apoptosis. Method A total of 40 female SD rats were randomly (random number)divided into the control group and the therapy group (ulinastatin 300 000 u/kg). The rat models of sepsis were produced by the classical method of cecal ligature and puncture (CLP), and the designed doses ulinastatin were given intra-peritoneally to the rats of the ulinastatin group and the same amounts of PBS (phosphate buffered solution) instead of ulinastatin were administered intra-peritoneally to the rats of the control group when the sepsis symptoms appeared usually in 3 hours after modeling. In 12 hours after treatment, lung tissues of rats in two groups were taken for observation under the transmission electron microscopy and detecting the levels of Bcl-2 and Bax protein in lung tissues by using immunohistochemical technique. The levels of the integrated optical density(IOD)of Bcl-2 and Bax protein were detected by using Image-pro plus software and the ratio of Bcl-2/Bax was calculated. Results Transmission electron microscope showed that lung tissue in control group had inflmmatory changes such as severe congestion and consolidation, and those changes in ulinastatin treatment group (300 000 u/kg)were significantly slighter. There were significant differences in the levels of antiapoptotic protein Bcl-2 in lung tissue of rats between two groups(P＜0.01), and the level of protein Bcl-2 in ulinas tatin group were higher than those in control group. The level of pro-apoptotic protein Bax in control group were higher than that in ulinastatin group (P＜0.01). The ratio of Bcl-2/Bax in ulinas tatin group was higher than that in control group (P ＜ 0.05).Conclusions Ulinastatin has protective effect on lung tissue in septic rats, and it may inhibit the inflammatory response and in the same time plays a role in inhibiting cell apoptosis.

Objective To observe the effect of integrated therapy of Chinese medicine and chemical drugs on adverse reaction and curative effect of initial treatment of secondary pulmonary tuberculosis. Methods Totally 1404 patients with secondary pulmonary tuberculosis and TCM lung consumption diagnostic criteria (syndrome of lung yin deficiency, qi-yin deficiency, yin-deficiency caused excessive fire) were chosen for single blind, randomized, controlled, multicenter clinical trials. Trial group was given 2HRZE/4HR, 1 time/day with Chinese medicine 2 or 3 times/day, and control group was given 2HRZE/4HR only for six months. The adverse reactions and clinical symptoms were observed to evaluate clinical efficacy and safety. Results In terms of reducing liver damage and other adverse reactions, the ratio of trial group had statistical difference with that of control group (P<0.001). In symptom scores of lung yin deficiency syndrome treated for 2, 4, 6 months, yin-deficiency caused excessive fire syndrome treated for 6 months, qi-yin deficiency syndrome treated for 4, 6 months, the differences between the two groups were significant (P<0.001). TCM syndrome curative effect between the two groups was statistical different (P<0.001). Safety evaluation result between the two groups was statistical different by tratified analysis (P<0.001). Conclusion Integrated therapy of Chinese medicine and chemical drugs can improve the symptoms and reduce adverse reactions caused by chemical drugs. It can enhance the curative effect and safety.

Objective To isolate fungi from sea sediment and sea water samples collected from the neritic environment in Qingdao, screen their antitumor activity and study on their fermentation condition. Methods The antitumor activity was assayed by flow cytometry in mouse tsFT210 cells. Results The medium added penicillin and streptomycin possesses good selectivity. 207 strains of fungi were isolated and among them, 19 strains showed antitumor activity, and one fungus(Z 83200)pocesses strong cell apoptosis inducing activity.