BACKGROUND: Mesenchymal stem cells (MSCs) have the abilities of self-renewal, multidirectional differentiation and immunomodulation, and have become the focus of current research. OBJECTIVE: To summarize the immunomodulation of MSCs to different immune cells and the clinical applications of MSCs in the treatment of immune-related diseases. METHODS: The first author searched the PubMed and the CKNI databases for relative articles from January 1974 to December 2016. The key words were mesenchymal stem cells, immunomodulation, MSC1 and MSC2, autoimmune diseases in English and Chinese, respectively. Finally, 52 representative articles were included. RESULTS AND CONCLUSION: MSCs can inhibit the function of T lymphocytes, reduce the activation, proliferation and antibody secretion of B lymphocytes, affect the polarization of macrophages, inhibit the maturation of dendritic cells, inhibit the proliferation and toxicity of NK cells, so MSCs have the great potential in the treatment of immune-related diseases. However, MSCs exhibit the opposite immunomodulatory abilities under different inflammatory microenvironments, and moreover the definite and controllable mechanism of this phenomenon is still unclear, Therefore, future investigations may focus on the specific mechanism of MSCs in the clinical treatment of immune-related diseases.

Background:With the deepening of researches on etiology of gastrointestinal bleeding,bleeding caused by pancreatic diseases has been understood better by the clinicians. Upper gastrointestinal bleeding (UGIB)is an uncommon but highly lethal complication of pancreatic diseases. Aims:To analyze the clinical characteristics of UGIB caused by pancreatic diseases for improving the diagnosis and management of this condition. Methods:A total of 22 inpatients who were diagnosed as UGIB caused by pancreatic diseases from Sep. 2010 to Sep. 2016 at Daping Hospital,the Third Military Medical University were recruited and analyzed retrospectively. Results:There were 15 males and 7 females;the disease was more prevalent in young patients than in middle-aged and elderly patients (45. 5% vs. 31. 8% and 22. 7%). The top five causes of bleeding were as follows:stress ulcer related to acute pancreatitis (36. 4%),pancreatic pseudocysts related to chronic pancreatitis (18. 2%),severe acute pancreatitis (13. 6%),post-operative bleeding related to pancreatic surgery (9. 1%)and left-sided portal hypertension (9. 1%). The diagnosis was commonly made by gastroscopy, abdominal contrast-enhanced CT and angiography. Ten patients received medical therapy only,6 were treated by surgical operation,5 by endoscopic hemostasis,and 1 by angioembolization. Hemostasis was achieved in 18 patients (81. 8%), and rebleeding occurred in 4 patients,of which two received medical therapy initially. Two elderly patients died of uncontrollable bleeding and multiple organ failure,respectively. Conclusions:UGIB caused by pancreatic diseases are prone to occur in young and middle-aged males. Pancreatitis and its complications are the major cause of this condition. Medical therapy is ineffective for most of the patients and a multidisciplinary approach of endoscopy,transarterial intervention and surgery is recommended.

Objective To establish a method for simultaneous determination for the contents of four flavones (ononin, calycosin, genistein and formononetin) of Hedysari Radix in Gansu Province with quantitative analysis of multi-components by single-marker (QAMS); To prove its feasibility and accuracy. Methods Calycosin was taken as internal standard substance. Relative correction factors (RCF) of ononin, genistein and formononetin to calycosin were established. The contents of ononin, calycosin, genistein and formononetin were determined to realize QAMS. Results RCF was with good repeatability. The results of QAMS were consistent with the results of the external standard method. Conclusion The method that determines the contents of ononin, genistein and formononetin with calycosin as internal standard substance, can be used for quantitative analysis of Hedysari Radix.

Aim To investigate the effects of chronic morphine treatment and withdrawal on the level of SNAPs in different brain regions of rats,including nucleus accumbens(NAc),caudate putamen(CPu) and hippocampus(Hip).Methods Adult male Wistar rats were randomly assigned into control,morphine and spontaneous withdrawal group.The morphine dependent rat model was established by subcutaneous morphine injection with increasing doses for 8 d,three times a day(8:00,12:00,and 18:00).The control group was injected with the same volume of normal saline.Rats in morphine group were killed 4 h after the last injection,and rats in withdrawl group were killed at indicated time.Control groups were paralleled with all treatment groups.The brains were removed and the NAc,CPu and Hip were separated.The expression of SNAPs mRNA and protein were determined by RT-PCR and Western blot.Results The expression of ?SNAP in CPu of morphine dependent rats was up-regulated by about 25%(P

Objective To build a method to simultaneously determine paeoniflorin, naringin, hesperidin, glycyrrhizic acid in Sinisan by HPLC, provide a reliable method for evaluation and effective quality control, and lay the foundation of material basis for efficacy research for TCM compound Sinisan.Methods The column was Kromasil C18 (4.6 mm×250 mm, 5μm);mobile phase was acetonitrile-0.05% phosphoric acid aqueous solution with gradient elution program;the flow rate was 1.0 mL/min;UV detection was performed at 240 nm;the detector drift tube temperature was set at 30℃.Results The linear ranges of paeoniflorin, naringin, hesperidin and glycyrrhizic acid were 0.00225-0.01125μg (r=0.999 7), 0.00390-0.00195μg (r=0.9997), 0.00198-0.00099μg (r=0.999 5), 0.00262-0.00131μg (r=0.999 7), respectively. The average recoveries of paeoniflorin, hesperidin, naringin and glycyrrhizic acid were 97.72% (RSD=1.02%), 98.45% (RSD=1.52%), 97.74% (RSD=1.63%), 98.34% (RSD=1.78%), respectively.Conclusion The method is accurate, simple, reliable and duplicable, and is available for the quality control of Sinisan.

AIM:To explore the molecular mecha-nism of Fuyangjing gel in the treatment of chronic eczema rats model based on janus protein kinase 1(JAK1)/signal transducer and activator of transcrip-tion 5(STAT5)signaling pathway.METHODS:Thirty-six SPF Wistar rats were randomly divided into nor-mal group,model group,Qingpeng ointment group,Fuyangjing gel low,medium and high dose groups.Except the normal group,the other groups of rats were treated with 2,4-dinitrochlorophenone solution to induce chronic eczema-like lesions on the back.After 3 weeks of modeling,Qingpeng ointment group and Fuyangjing gel low,medium and high dose groups were respectively treated with corresponding drugs.The model group was smeared with blank gel matrix once a day for 2 weeks,while the normal group was not treated.The severity and pathological changes of back le-sions in chronic eczema rats were observed.The ex-pression of phosphorylated protein tyrosine kinase 1(p-JAK1)and phosphorylated signal transduction and transcriptional activator 5(p-STAT5)in rat dor-sal skin was detected by Western blot.Detection of thymic stromallymphopietin(TSLP),JAK1,STAT5,in-terleukin-10(IL-10)and IL-17 mRNA expression lev-els in rat back skin by qRT-PCR;The levels of IL-4,IL-6,IL-10,IL-13 and IL-17 in serum of rats were deter-mined by enzyme-linked immunosorbent assay(ELI-SA).RESULTS:Compared with normal group,the se-rum levels of IL-4,IL-6,IL-13 and IL-17 in model group were significantly increased,while IL-10 lev-els were significantly decreased(P＜0.05).The ex-pression levels of p-JAK1,p-STAT5 protein and TSLP,JAK1,STAT5 and IL-17 mRNA in back lesions were significantly increased,while IL-10 mRNA levels were significantly decreased(P＜0.05).Compared with model group,serum levels of IL-4,IL-6,IL-13 and IL-17 in Qingpeng ointment group and Fuy-angjing gel low,medium and high dose groups were significantly decreased,while IL-10 levels were significantly increased(P＜0.05).The expres-sion levels of p-JAK1,p-STAT5 protein and TSLP,JAK1,STAT5 and IL-17 mRNA in back lesions were significantly decreased,while the mRNA levels of IL-10 were significantly increased(P＜0.05).The serum levels of IL-4,IL-6,IL-13 and IL-17 in Qingpeng oint-ment group were decreased,while IL-10 levels were increased(P＜0.05).The expression levels of p-JAK1,p-STAT5 protein and TSLP,JAK1,STAT5 and IL-17 mRNA in back lesions were decreased,while the mRNA levels of IL-10 were increased(P＜0.05).Com-pared with Qingpeng ointment group,there were no significant differences in serum levels of IL-4,IL-6,IL-10,IL-13 and IL-17 in Fuyangjing gel high-dose group(P＞0.05).There were no significant differenc-es in the expression levels of p-JAK1,p-STAT5 pro-tein and TSLP,JAK1,STAT5,IL-10 and IL-17 mRNA in back lesions(P＞0.05).CONCLUSION:Fuyangjing gel may play a role in the treatment of chronic eczema by regulating the expression of JAK1/STAT5 signal-ing pathway related inflammatory factors,proteins and genes.

Boao Lecheng International Medical Tourism Pilot Area is the only administrative area in China where the pilot application of real-world data is performed. Based on the special healthcare policy in Boao Lecheng, conducting real-world data study to provide real-world evidence for the clinical evaluations and approvals of innovated medical products has become an important field that supports the reform of China's evaluation and approval system of medical products. Trustworthy real-world evidence needs to rely on both high-quality real-world data and reasonable and rigorous study designs. Based on the real-world data research guidelines and specifications issued by relevant academic research and regulatory authorities both at home and abroad, combined with the special policy environment of Boao Lecheng and previous practice experience, this paper summarizes the study designs of real world data in Boao Lecheng and discusses the key considerations of different study design in the context of special healthcare policies in Boao Lecheng in order to provide reference for the further study of real-world data.

Objective To observe the effect of arsenic exposure to drinking water on thelevel of histone 3 lysine 4 trimethylation (H3K4me3) and histone 3 lysine 79 trimethylation (H3K79me3) in peripheral blood leukocytes of human,and to analyze the relationship between arsenic exposure and H3K4me3,H3K79me3 modification levels.Methods A cluster sampling survey was carried out in typical endemic arsenicosis areas of Shanxi and Jilin provinces.Two hundred eighty-one local residents with a drinking water age of ≥ 10 years were selected as the survey subjects.According to the arsenic content of drinking water,the tested population was divided into control group (water arsenic content ≤0.01 mg/L,60 cases),low water arsenic exposure group (＞ 0.01-0.05 mg/L,61 cases),medium water arsenic exposure group (＞ 0.05-0.10 mg/L,50 cases),and 110 cases of high water arsenic exposure group (＞ 0.10 mg/L).Drinking water samples,immediate urine samples and peripheral blood samples were collected from the subjects.Arsenic content in drinking water and urinary arsenic content were determined via the atomic fluorescence method;histone H3K4me3 and H3K79me3 in peripheral blood leukocytes were determined by dot blot hybridization (Dot Blotting).Results There were no statistically significant differences in age (61.50,60.00,59.50,59.50 years old),different gender (male:20,27,17,40 cases,female:40,34,33,70 cases),body mass index (BMI),smoking and drinking status between the control group,low,medium and high water arsenic exposure groups.Water arsenic content in the control group,low,medium and high water arsenic exposure groups (median:0.005,0.024,0.076,0.150 mg/L),urinary arsenic content (0.011,0.018,0.061,0.134 mg/L),and water arsenic cumulative exposure levels (0.342,1.641,5.273,7.716 mg) were compared between groups,the differences were statistically significant (H =256.041,88.615,218.610,P ＜ 0.01).In the control group,low,medium and high water arsenic exposure groups,the modification levels of H3K4me3 (0.100,0.059,0.083,0.083)and H3K79me3 (0.049,0.036,0.055,0.052) in peripheral blood leukocytes were not significantly different (H =1.488,2.097,P ＞ 0.05).The levels of H3K4me3 and H3K79me3 in peripheral blood leukocytes were positively correlated with water arsenic content,urinary arsenic content,water arsenic cumulative exposure levels (r =0.245,0.221;0.299,0.318;0.149,0.149;P ＜ 0.01 or ＜ 0.05);there was a positive correlation between H3K4me3 and H3K79me3 modification levels (r =0.811,P ＜ 0.01).Conclusion There is a positive correlation between arsenic exposure through drinking water and the levels of H3K4me3 and H3K79me3 in the peripheral blood leukocytes of the population,but it is necessary to expand the sample size for further study.

OBJECTIVE：To investigate the in vitro quality consistency of domestic Nitroglycerin table t imitative preparation and reference preparation （original drug ）. METHODS ：The contents of nitroglycerin and related substances in 1 batch of Nitroglycerin tablet reference preparation （manufacturer A ）and 4 batches of imitative preparation （manufacturer B ，C，D，E） were determined according to Nitroglycerin Tablet Import Drugs Registration Standard JX 20010267. The paddle method of dissolution determination method was adopted ，with the rotating speed of 50 r/min. HPLC method was adopted to determine the dissolution amount of 5 batches of above preparations in 4 kinds of dissolution mediums （pH 1.2 hydrochloric acid solution ，pH 4.0 acetate buffer solution ，pH 6.8 phosphate buffer solution ，water） within 10 min.The accumulative dissolution rate was calculated，and dissolution curves of samples were drawn.The similarity of the dissolution curves was evaluated by calculating similarity factor （f2）of 2，5，8 min accumulative dissolution rate. RESULTS ：The contents of nitroglycerin in the preparations from manufacturer A ，B，C，D，E were 99.8％，98.3％，94.0％，93.3％，96.7％，respectively（n＝2）；the contents of related substance were 0.46％，0.55％，0.63％，0.72％，0.49％，respectively（n＝2）. Using reference preparation of manufacturer A as control，f2 of imitative preparation from manufacturer B ，C，D，E were 74，28，25，67 in pH 1.2 hydrochloric acid solution ；76， 26，28，84 in pH 4.0 acetate buffer solution ；79，39，35，71 in pH 6.8 phosphate buffer solution ；69，32，37，62 in water ， respectively. CONCLUSIONS ：The method is suitable for in vitro quality consistency evaluation of Nitroglycerin table timitative preparation. Compared with reference preparation ，the contents of main components in the imitative preparations from manufacturer C，D are lower ；in vitro dissolution curves of those imitative preparation are not similar to reference preparation .

Objective:To investigate the association of single nucleotide polymorphism at the estrogen receptor 1(ESR1) gene rs1801132 with the risk of brick-tea type skeletal fluorosis.Methods:The typical brick-tea type fluorosis areas in Qinghai, Xinjiang, and Inner Mongolia were selected as the survey sites for a cross-sectional study. An epidemiological questionnaire was conducted by the staffs on the sites for participants older than 16 years, and physical examination and X-ray diagnosis were performed. Brick tea, blood, and urine samples were collected at the same time. The diagnosis of skeletal fluorosis through X-ray was based on the "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS/T 192-2008); The determination of tea's fluoride and urinary fluoride was performed by fluoride ion-selective electrode method; gene sequencing analysis of rs1801132 locus of ESR1 gene was done by Sequenom MassARRAY flight mass spectrometry system.Results:A total of 994 patients were included in this study. The total prevalence of skeletal fluorosis was 23.9% (238/994). The prevalence of skeletal fluorosis in Tibetans(39.9%, 123/308) was higher than those of Mongolian and Han nationality [22.2% (58/261), 13.4% (57/425), χ 2=20.435, 67.811, P < 0.05]. Based on binary logistic analysis, the daily tea fluoride intake ≤ 3.5 mg, urinary fluoride content ≤1.6 mg/L, and age ≤45 years were used as the reference groups, and then, when the daily tea fluoride intake > 7.0 mg ( OR=2.865, 95% CI: 1.923-4.268), urinary fluoride content > 1.6-3.2 mg/L ( OR=2.368, 95% CI: 1.686-3.326) and > 3.2 mg/L ( OR=3.559, 95% CI: 2.401-5.276), the age > 45-65 years old ( OR=2.361, 95% CI: 1.603-3.477) and > 65 years old ( OR=4.556, 95% CI: 2.845-7.296), the risk of fluorosis was higher than that of the reference group, respectively. When the daily tea fluoride intake was > 3.5-7.0 mg and the level of urinary fluoride was > 1.6-3.2 mg/L, G allele had a protective effect on skeletal fluorosis in Mongolian population (adjusted OR=0.207, 95% CI: 0.044-0.974); when the daily tea fluoride intake was > 3.5-7.0 mg, gender was male group, G allele had a protective effect on skeletal fluorosis in Han population (adjusted OR=0.315, 95% CI: 0.112-0.887). Conclusion:The single nucleotide polymorphism of the rs1801132 locus at the ESR1 gene may be associated with the risk of susceptibility to brick-tea type skeletal fluorosis in Mongolian and Han nationality.