Objective In order to evaluate that whether Pluronic P85 coated poly(butylcyanoacrylate) nanoparti-cles was able to deliver antiepileptic drug phenytoin into the brain va bypassing mesial temporal lobe epilepsy (MTLE)-induced Pgp in a rat model of MTLE. Methods The rat model of MTLE, induced by li-pilocarpine, was divided in-to two groups (6 for nanoparticle drug group and 7 for PHT drug group). Immunohistochemistry assay was performed to detect Pgp expression at the hippocampus. Nanoparticles were prepared by interfacial polymerization method. Dialysate samples of brain were collected at 30, 60, 120, 180, 240 and 300 min after drug administration by microdialysis tech-nology. Samples were analyzed by high performance liquid chromatography (HPLC). Results The area under the curve (AUC) ratio of brain/plasma in Nanoparticle drug group was 0.370.10 which was significantly higher compared with 0.190.06 in conventional PHT drug group (P<0.05). The Pgp immunopositive area, as assessed by analysis of labeled surface area, was higher in the DG, CA3 and CA1 sector in the hippocampus of MTLE rats when compared to the normal rats. Conclusions Pluronic P85 coated PBCA nanoparticles can significantly deliver PHT into brain via bypassing MTLE-induced Pgp in a rat model of MTLE.

Objective To express the receptor binding domain (RBD) protein of the Middle East respiratory syndrome coronavirus (MERS-CoV) and to characterize the antigenicity of the purified recombi-nant protein. Methods The codon-optimized gene encoding the RBD protein of MERS-CoV was synthesized and then cloned into the pET30a ( +) vector to construct the recombinant expression plasmid. The trans-formed E. coli BL21 (DE3) strains carrying expression plasmid were induced by IPTG under different condi-tions. The expressed products were purified by using nickel affinity chromatography and further analyzed by SDS-PAGE and Western blot assay. Indirect ELISA was performed to analyze the antigenicity and specificity of RBD proteins expressed in prokaryotic expression systems in human serological test. Results The recom-binant RBD proteins were mainly expressed as conclusion body in an optimal induction condition of 37℃ and 0. 5 mmol/ L IPTG for 4 h. The high purified recombinant RBD proteins were obtained through denaturation and renaturation with a relative molecular mass of about 29×103 . Results of the Western blot assay showed that the recombinant RBD proteins could have specific reaction with the serum samples collected form mice with MERS-CoV infection. Indirect ELISA revealed that the RBD proteins expressed in the prokaryotic ex-pression system showed better sensitivity and specificity in the detection of antibodies against MERS-CoV in human serum samples. Conclusion This study reported the prokaryotic expression and purification of RBD protein of MERS-CoV for the first time, which might pave the way for further investigation on immunological detection of MERS-CoV and development of vaccines against MERS-CoV infection.

Objective To assess the therapeutic effects of flupentixol and melitracen tablets combined with Saccharomyces boulardii on patients with diarrhea-predominant irritable bowel syndrome (IBS) accompanied with anxiety and depression.Methods This multi-center,randomized,prospective study enrolled 84 patients with diarrhea-predominant IBS who were divided into combined treatment group (42 patients) and control group (42 patients).Saccharomyces boulardii was administrated in both of the groups,and flupentixol and melitracen was added in combined treatment group.The treatment course was four weeks.The gastrointestinal symptoms and mood disorders were evaluated before treatment,one week and four weeks after treatment.Adverse reactions were also observed.Chi-square test was performed for statistical analysis.Results At the end of one week after treatment,the efficacy rates of gastrointestinal symptoms improvement of combined treatment group and control group were 31.0％ (13/42) and 23.8％ (10/42),and there was no statistically significant difference (P＞0.05).At the end of four weeks after treatment,the efficacy rate of gastrointestinal symptoms improvement of combined treatment group was 92.5％ (37/40),which was higher than that of control group (73.2％,30/41),and the difference was statistically significant (x2 =5.291,P =0.037).At the end of one week after treatment,the efficacy rates of Hamilton Depression Scale score improvement of combined treatment group and control group were 31.6％ (12/38) and 12.1％ (4/33),and there was no statistically significant difference (P＞0.05).At the end of four weeks after treatment,the efficacy rates of Hamilton Depression Scale score improvement of combined treatment group was 63.9％ (23/36),which was higher than that of control group (34.4％,11/42),and the difference was statistically significant (x2 =6.433,P=0.043).At the end of one week and four weeks after treatment,the efficacy rates of Hamilton Depression Scale score improvement of combined treatment group were 35.7％ (15/42) and 80.0％ (32/40),which were higher than those of control group (15.4％,6/39 and 34.2％,13/38),and the differences were statistically significant (x2 =9.759,P=0.007; x2 =17.105,P＜0.01).One week after treatment,the adverse events rates of combined treatment group and control group were 4.8％ (2/42) and 4.8％ (2/42) ; four weeks after treatment,the adverse events rates of combined treatment group and control group were 2.5％ (1/40) and 2.4％ (1/41).There was no statistically significant difference in adverse events rates between two groups (both P＞0.05).Conclusions Flupentixol and melitracen combined with Saccharomyces boulardii treatment could not only improve the anxiety and depression symptoms of patients with diarrhea-predominant IBS,but also effectively improve gastrointestinal symptoms.The efficacy of combined treatment is better than monotherapy Saccharomyces boulardii alone treatment.

Objective: To analyze the prognostic factors of non-Hodgkin's lymphoma(NHL)and to investigate the prognostic value of peripheral blood absolute lymphocyte count(ALC)at admission for patients with NHL. Methods: Clinical features and follow-up data of 108 patients with pathologically confirmed NHL seen in our hospital between January 2000 and January 2008 were reviewed.SPSS14.0 package was used for statistical analysis.Kaplan-Meier was applied to assess the survival probability.All parameters statistically significant concluded by univariate analysis were then computed as co-variates for multivariate analysis with Cox regression model. Results: The ratio of males to females was approximately 1.5:1.The median age of patients was 48 years.Before treatment.the Ann Arbor clinical classification showed that 61.1% of the cases were of stage Ⅰ and Ⅱ.Approximately 93%of the patients had ECOG performance status(PS)score of 0-1 and 19.2%of the cases had elevated serum lactate dehydrogenase(LDH).According to intemational prognosis index score.80.6%of the patients were in a low risk group.At admission，35.2%of the cases had ALC≤1×10~9/L.Hemoglobin (Hb)≤110g/L and B symptoms were seen in 29.6%and 26.9%of the patients.The mean Hb was 129.2±17.5g/L in cases with ALC>1×10~9/L(n=70)and 98.1±20.6g/L in cases with ALC≤1×10~9/L(n=38),with a statistically significant difference between the two groups(P<0.05).With a median follow-up duration of 2 years，the median overall survival(OS)time was 2.3 years for all patients.The 2-year and 5-year OS rates were 73.2%and 39.6%，respectively.ALC≤1×10~9/L,Hb≤110g/L,B symptoms and intemational prognostic index(IPI)≥2 were statistically significant unfavorable prognostic factors for NHL revealed by univariate analysis.Multivariate analysis showed that ALC≤1×10~9/L,B symptoms and IPI ≥2 were statistically significant unfavorable prognostic factors for NHL. Conclusion: ALC and B symptoms may be prognostic factors independent of IPI for NHL.Evaluation of the prognosis with IPI,ALC，and B symptoms is of clinical value for individualized therapy of NHL patients.

Objective To investigate the diagnostic value of capsule endoscopy (CE), CT enterography (CTE), ileocolonoscopy and small bowel follow through (SBFT) for small bowel Crohn's disease (CD). Methods Fifty-seven consecutive patients with CD underwent ileocolonoscopy, CTE, CE, and SBFT. It included the presence of the following symptoms and signs: abdominal pain, weight loss,diarrhea, fever and positive fecal occult blood test. The location and the characteristics of intestinal and extra-intestinal lesions detected by four techniquks were compared. The proportions of patients with positive findings using each examination were compared. Results Of the 57 patients, 50 underwent ileocolonoscopy, terminal ileum lesion was found in 33 patients (66. 00% ), the remaining 17 (34.0%)were normal; among 34 patients who had CTE, 29 of small bowel lesion were found (85. 29% ); CE were performed in 27 patients, due to prolonged gastric transit one time, the capsule did not reach the cecum in one patient during battery lifetime. CE showed small bowel lesion in 26 patients (96.30% ); SBF was performed in 39 patients and 26 of small bowel lesion were detected (66. 67% ). CE had the highest diagnostic yield for CD and ileocolonoscopy had the lowest, and there were statistically significant difference among the 4 examinations (P = 0. 006 ). The combinded positive rates of two methods were: CE + CTE 92. 86% (13/14), SBFT + CTE 90. 91% (20/22), CE + ileocolonoscopy 95. 65% (22/23), CE + SBFT100% (17/17), ileocolonoscopy + CTE 89. 66% ( 26/29 ), ileocolonoscopy + SBFT 77.78% ( 28/36 ), but there were no significant differences between each two examinations. Conclusion CE, CTE have a higher yield in depicting mild to moderate finding of CD than SBFT. CE is better for assessing early mucosal disease,whereas CTE is better for detecting transmural and extraluminal abnormalities. Most important, CE plus CTE may depict nonobstructive CD of the small bowel when conventional techniques such as ileocolonoscopy or SBFF have negative or inconclusive finding. CE provides us explanations for the symptoms of patients, decision to follow up or therapy.

Objective To summarize the clinical features, diagnosis and treatment of autoimmune pancreatitis (AIP). Methods From March 2003 to January 2008, a total of 16 cases of AIP were reviewed retrospectively. Results The ratio of male: female was 15:1, with a mean age of 61 years old (range:47-79 years old). Jaundice was the main clinical presentation in 81.2% patients. 68.8% patients presented with high serum gammaglobulin, while 66.7% with high serum IgG, 56.2% with elevated ESR, 50.0% with positive rheumatoid factor(RF), 43.7% with eosinophilia, 26.7% with positive antinuclear antigen(ANA),31.2% with elevated lipase, 18.7% with elevated amylase, and 25.0% with elevated CA19-9. 93.7%patients showed diffuse swelling of the pancreas on CT and/or endoscopic ultrasound. Stricture of the main pancreatic duct was seen in 100% patients. Distal common bile duct stricture was seen in 87.5%, while thickened wall of bile duct was seen in 50%. Histological findings of the pancreas EUS-FNA showed nonspecific results in one patient, while no tumor cell was detected in other 5 patients; lymphocytes infiltration was noted in 3 patients; pancreatic fibrosis was seen in 2 patients. 75.0% patients was found to have diabetes or abnormal sugar tolerance, enlargement of the celiac lymph nodes in 43.7%, splenic vein or inferior cava vein involvement in 42.9%, swelling of the maxillary glands in 18.7%, the lacrimal glands in 12%. Prednisone was given to 11 patients, among them 5 patients underwent endoscopic stent placement, and 10 patients responded well while 1 patient discontinued therapy due to intolerance. 2 patients underwent endoscopic stent placement alone and jaundice disappeared. 3 patients received conventional medical treatment. Steroid therapy exerted different effects on levels of the blood glucose, the enlarged maxillary and lacrimal glands improved after steroid therapy. Conclusions AIP occurred in middle aged and senior male predominantly, painless obstructive jaundice was the main clinical presentation, and patients may be accompanied with elevated levels of IgG, hypergammaglobulin, positive RF and ANA, diffuse or focal pancreatic enlargement, pancreatic duct stricture and distal common bile duct stricture. Stent placement could improve the symptoms, and steroid therapy was effective.

The surveyof the situation of medical treatment for foreign students in Chongqing shows that there are certain problems in schools,hospitals and students etc.To strengthen the public health building,to improve conditions of medical services,to provide the necessary guide for medical treatment,and to enhance foreign students'self-adaptive capacities and so on may help solve these problems and improve the foreign students'health quality.

In this study, we evaluated the difference ot biological characteristics in the MERS-CoV infected mice model in prior to transduction with different dosage of human DPP4. Firstly, we transduced different dosage of DPP4 (high or low) into mice, and then challenged them with MERS-CoV in order to establish the model. After establishment of mice model, we observed the clinical signs of disease, virus replication, immunopathogenesis and antibody response. The results indicated that the infected mice showed typical pneumonia, virus replication, histological lesions, and neutralizing antibody production. Moreover, the high dosage group was superior to the low dosage group. Fourteen days after infection, the specific antibody to virus structural protein and neutralizing antibody were analyzed, the high dosage group induced higher level antibody. In summary, the MERS-CoV infected mice model were established prior transduction with DPP4, and the level of DPP4 influenced the clinical signs of disease, virus replication and antibody response in this model.
Animals ; Coronavirus Infections ; enzymology ; genetics ; pathology ; virology ; Dipeptidyl Peptidase 4 ; genetics ; metabolism ; Disease Models, Animal ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Middle East Respiratory Syndrome Coronavirus ; genetics ; physiology

Objective:To construct the molecular transmission network of human immunodeficiency virus type 1 (HIV-1) epidemic strains in northern Zhejiang Province (Jiaxing City and Huzhou City) and to explore the HIV-1 transmission characteristics in this region.Methods:A total of 371 newly diagnosed human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in Jiaxing City and Huzhou City in 2017 were included as study subjects, and the blood samples were collected and the basic demographic and epidemiological information were obtained. RNA in plasma was extracted, and the pol region gene sequence was amplified by reverse transcriptase polymerase chain reaction (RT-PCR) and nested polymerase chain reaction (PCR) to construct phylogenetic tree for identifying subtypes. The pairwise genetic distances were calculated, and the optimal threshold of genetic distance was selected, and finally the molecular transmission network was constructed. Chi-square test was used for statistical analysis. Results:The pol region gene sequences of 336 samples were successfully obtained, and 11 subtypes were detected, mainly including circulating recombinant form (CRF)07_BC (40.8%, 137/336) and CRF01_AE (31.2%, 105/336). Based on the 1.0% genetic distance threshold, the molecular transmission network of HIV-1 was plotted. A total of 38 transmission clusters (cluster sizes ranging from two to 28) including 119 patients were found, with males predominantly (82.4%, 98/119) and most of the patients aged over 40 (include 40) years old (52.9%, 63/119), mainly infected with CRF07_BC subtype (57.1%, 68/119) and CRF01_AE (24.4%, 29/119). The clustering rate of CRF07_BC (49.6%, 68/137) was significantly higher than that of CRF01_AE (27.6%, 29/105), the difference was statistically significant ( χ2=5.27, P=0.022). Two large clusters C1 (28 cases) and C2 (11 cases) were identified, the majority of which were men who have sex with men (17 cases and seven cases, respectively). High-risk cases generally sought sexual partners in local or nearby cities through mobile phone dating software, of which the infected sequences mostly had high homology with other economic developed regions (Guangdong Province, Beijing City and Hangzhou City, etc.). Conclusions:The HIV-1 subtypes are diverse in Jiaxing City and Huzhou City, mainly CRF07_BC and CRF01_AE. The HIV-1 transmission networks are complex, among which high-risk cases may be the key factor leading to the HIV-1 epidemic in the region. Therefore, it is urgent to deepen the transmission network monitoring and formulate timely precise intervention and prevention strategies.

ObjectiveTo unify the definitions of colonoscopic characteristics of Crohn disease (CD) and intestinal tuberculosis ( ITB),and to evaluate colonoscopic and clinical features in the differential diagnosis of CD and ITB.MethodsA collaborative group composed of 10 experts from 5 hospitals voted to identify and confirm the colonoscopic characteristics.Clinical and colonoscopic characteristics were analyzed,thereafter,characteristics were scored based on different diagnostic specificity.ROC curve was used for determining the cutoff point to differentiate CD from ITB.ResultsFirstly,standard endoscopic images and descriptions were determined.Secondly,colonoscopic parameters which were significantly different between the CD and ITB patients included the follows:involvement of more than four intestinal segments,anorectal involvement,longitudinal ulcers,cobblestone appearance and transverse ulcers.Clinical findings which were significantly different between the CD and ITB patients included active pulmonary tuberculosis,PPD-test strong positive,anal fistula/perianal abscess and extra-intestinal manifestations in CD.4.4％(6/136) patients were confirmed by histological evidence of caseating granulomas.By using our scoring system,39.7％ (54/136) confirmed diagnoses and 18.4％ (25/136) suspected diagnoses were made in patients without histological evidence.ConclusionIdentification of colonoscopic characteristics and unification of the colonscopic diagnostic criteria were helpful in the differential diagnosis between CD and ITB.The differential diagnosis rate could he improved by using the scoring system.Half cases could not be confirmed even with combined pathology and the scoring system,so a more comprhensive scoring system would be warranted.