Adolescent ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Lymphohistiocytosis, Hemophagocytic ; genetics ; Mutation ; Signaling Lymphocytic Activation Molecule Associated Protein

Objective To observe the changes of the peripheral blood T helper (Th)17 cells/regulatory T cells (Treg) ratio in patients with anti‐tuberculosis drug‐induced liver injury ,and to explore the relationship between Th17/Treg ratio and liver function . Methods Ninety inpatients with the diagnosis of secondary pulmonary tuberculosis (TB) from Affiliated Hospital of Zunyi Medical College from Feb .2013 to Mar .2015 were included in this study .All these patients had normal base line liver function .After 2 weeks of anti‐TB chemotherapy ,21 patients with alanine transaminase (ALT) and/or aspartate aminotransferase (AST) ≥2 × upper limit of normal (ULN) were defined as TB with liver injure group ,the other 69 patients with ALT and/or AST<2 × ULN were defined as TB with non‐liver injured group .Before treatment and two weeks after anti‐TB therapy ,the peripheral blood Th17/Treg ratios and liver functions of all patients in both groups were detected in order to compare the changes of Th17/Treg ratios pre and post anti‐TB chemotherapy and to explore the relationship between Th17/Treg ratio and ALT/AST levels .Student′s t test was used for statistical analysis ,and Pearson correlation analysis was used for correlation test .Results Before treatment ,there was no statistical significance of Th17 ,Treg and Th17/Treg ratio between groups (P> 0 .05) .The Th17 levels in TB with liver injured group ([2 .522 ± 0 .388]/mL vs [2 .075 ± 0 .369]/mL ,t=3 .633 ,P<0 .01) and TB with non‐liver injured group ([2 .326 ± 0 .348]/mL vs [1 .929 ± 0 .402]/mL ,t= 6 .468 , P< 0 .01) ,and Th17/Treg ratios in both groups(0.618±0.104vs0.489±0.107,t=3.553,P<0.01 ;0.554±0.108vs0.450±0.098,t=6 .353 ,P<0 .01) were all increased after anti‐TB chemotherapy ,with statistically significant differences . However ,there was no statistical significance of Treg levels pre and post anti‐treatment in both groups (both P>0 .05) .The Th17 level and Th17/Treg ratio in TB with liver injured group were significantly higher than those in TB with non‐liver injured group (t= 2 .203 , P< 0 .05 and t= 2 .345 , P< 0 .05 , respectively) .In liver injured group ,the Th17/Treg ratio was positively correlated with ALT level (r=0 .849 ,P=0 .044) ,but not with AST level (P>0 .05) .Conclusion The changes of Th17/Treg ratio are related with anti‐TB drug‐induced liver injury in patients with secondary pulmonary tuberculosis .

It is particularly important to confirm that whether subjects were repeated to participate in the clinical trial, the time interval from the last dose in the recent clinical trial, whether the physical conditions of subjects accord with the clinical trial protocol in phase I clinical trials and so on.This paper will introduce two types of the subject database, one was established by our hospital, another one is subject networking database, and will introduce the operation mode, the present situation of subjects screening under the database management. To explore the existing problems, optimize the use of subject database and give long-term prospects of subject networking database.

Objective: To observe the impact of high thoracic epidural blockade (HTEB) on atrial autonomic nerve remodeling in dogs with atrial ifbrillation (AF) induced by long-term rapid right atrial appendage pacing and to explore the effect of nerve growth factor (NGF) on atrial autonomic nerve remodeling.
Methods: AF model was established by consistent rapid atrial pacing for 6 weeks. 18 experimental dogs were randomly divided into 3 groups: Sham group, the dogs had no pacing while received normal saline injection; Control group, the dogs had pacing and normal saline injection; HTEB group, the dogs had pacing and 0.5% lidocaine injection for HTEB.n=6 in each group. Atrial myocardium collagen volume fraction (CVF) was examined by Masson staining; sprouting of NGF related protein 43 (GAP43) and tyrosine hydroxylase (TH) were assessed by immunohistochemistry; protein expressions of NGF, GAP43 and TH were measured by Western blot analysis.
Results: Compared with Sham group, HTEB group showed decreased CVF and sprouting of GAP43, TH,P<0.05;reduced protein expressions of NGF, GAP43 and TH,P<0.05-0.01. Compared with Sham group, HTEB group presented increased CVF and sprouting of GAP43, TH,P<0.05-0.01; elevated protein expressions of NGF, GAP43 and TH,P<0.05.
Conclusion: Long-term rapid atrial pacing induced AF dog had inhomogeneous sprouting of atrial myocardial nerve which may cause autonomic nerve remodeling; NGF played the important role in such process. HTEB could effectively inhibit NGF up-regulation and suppress the autonomic nerve remodeling in experimental dogs.

Notch signaling pathway consists of three parts: Notch receptor, Notch ligand and intracellular effector. Notch is a family of transmembrane proteins that function both as cell surface receptors and transcription regulators. As the first human gene of this family, Notch1 was discovered in 1991 through the analysis of the chromosomal translocation t(7;9) (q34;q34.3) observed in patients with T-cell acute lymphoblastic leukemia (T-ALL). Since then Notch signaling has been implicated in multiple processes that govern normal morphogenesis, differentiation, cell proliferation and apoptosis. At the same time a role of Notch in the pathogenesis of hematologic and solid malignancies has become apparent. The identification of activating mutations in Notch1 were discovered in over 50% of T-ALL patients. However, whether the mutation in Notch1 is an early event or an secondary event is still unknown. It is becoming increasingly evident that Notch signaling can be both oncogenic and tumor suppressive. This review focuses on the recent findings regarding the Notch signaling during the development and progression of different kinds of hematologic malignancies, the types of mutations in Notch1 in T-ALL and the relationship between Notch signaling pathway and other signaling pathways.In addition, the clinical prospects of Notch inhibitors also are discussed.
Humans ; Neoplasms ; Receptor, Notch1 ; Signal Transduction

Objective To investigate the trend of liver function changes in untreated adult patients with Graves’ disease in China, and to analyze the associated factors. Methods Patients with newly diagnosed as well as recurrent Graves’ disease from January 2006 to August 2014 were enrolled. They were over 18 years old and did not receive any treatments, Examination of liver function, thyroid function, and thyroid related antibodies as well as tests regarding virus hepatitis were performed. Results A total of 1 254 patients were enrolled. 33 patients with virus hepatitis were ruled out. Ultimately, 1 221 patients matched the criteria of our trial, with 347 males and 874 females [(39. 3 ± 9. 5) year old]. After inclusion, they were assigned to 2 groups according to their liver function results(605 in normal group and 616 in abnormal group). Compared to normal group, patients in the abnormal group were older [(40. 1 ± 9. 2 vs 38. 5 ± 8. 7) year old, P<0. 05] and with higher proportion of females(81. 8% vs 61. 2% , P<0. 05). Regarding the thyroid function and related antibody tests, some patients yielded results that were extremely high so as to exceed the upper limit of the normal range. These patients were more frequently seen in the group with abnormal liver function. The patients whose thyroid function parameters exceeded the upper limit had higher level of alanine aminotransferase[ALT,(37. 69 ± 7. 51 vs 31. 90 ± 5. 95) U/ L, P<0. 05], aspartate aminotransferase[AST, (31. 97 ± 5. 09 vs 27. 88 ± 3. 82) U/ L, P<0. 05], direct bilirubin[DBiL, (5. 58 ± 0. 77 vs 4. 54 ± 0. 71) μmol/ L, P<0. 05]than the group whose thyroid function on the detected range. In the patients with all results detected, patients in abnormal liver function group had higher level of triiodthyronine[T3 , (5. 42 ± 0. 29 vs 4. 94 ± 0. 33) nmol/ L, P<0. 05], thyroxin[T4 ,(217. 53 ±14. 32 vs 204. 22 ±13. 54) nmol/ L, P<0. 05], free triiodthyronine[FT3 ,(15. 88 ± 2. 86 vs 14. 48 ±4. 83) pmol/ L, P<0. 05], free thyroxin[FT4 ,(48. 91 ±8. 45 vs 42. 95 ±6. 14) pmol/ L, P<0. 05], thyroid peroxidase antibody[ TPOAb, (402. 75 ± 89. 99 vs 210. 70 ± 44. 63) IU/ ml, P < 0. 05] and thyrotrophin receptor antibody[TRAb,(14. 08 ± 5. 24 vs 9. 04 ± 2. 58) IU/ L, P<0. 05]. Multivariate logistic regression analysis revealed that patients’ age(OR=0. 98, 95% CI 0. 97-0. 99), gender(OR=0. 94, 95% CI 0. 91-0. 97), level of FT4 (OR=3. 08, 95% CI 2. 19-4. 32), TPOAb(OR = 0. 98, 95% CI 0. 97-0. 99), and TRAb(OR = 1. 07, 95% CI 1. 01-1. 12) were independent risk factors of their liver dysfunction. Conclusion Graves’ disease may lead to liver dysfunction, which is much more common and severe in elder and female patients, as well as patients who are suffering from hyperthyroidism and raised level of thyroid related antibodies.

Abstract: Schistosomiasis, an important zoonotic parasitic disease, is one of the six major tropical diseases identified by WHO, and also one of the most important parasitic diseases for prevention and control in China. After more than 70 years of efforts, the prevention and control of schistosomiasis in China has made great achievements, and the current epidemic of schistosomiasis in China has entered an extremely low epidemic state, but the distribution base of the only intermediate host of schistosomiasis, Oncomelania hupensis, is still large. For now, the techniques used to monitor schistosomiasis have shortcomings such as time-consuming, laborious and low sensitivity, which cannot meet the current needs of China. Environmental DNA (eDNA) refers to DNA that can be extracted from environmental samples (such as soil, water or air) without isolating any target organisms, which is a complex mixture of genomic DNA and its degradation products from different organisms in the same environment. eDNA technology can reflect the community or species composition information in the ecosystem through DNA extraction and detection of environmental samples. Compared with traditional biological monitoring methods, eDNA technology has the advantages of high efficiency, high sensitivity and environmental friendliness. eDNA has been successfully used for the specific detection of Schistosoma mansoni, Schistosoma haematobium and Schistosoma japonicum. This paper reviews the current detection methods of eDNA, the application and technical limitations of eDNA technology in schistosomiasis monitoring, aiming to provide scientific reference for research in the field of schistosomiasis surveillance.

Genomic DNA sequence analysis of phytochrome like photoreceptors in a number of bacteria revealed several open reading frames (ORFs) encoding proteins with amino acid sequences homologous to plant phytochromes. The phytochrome like photoreceptors, collectively called bacteriophytochromes, contain an N-terminal domain homologous to the chromophore-binding domain (CBD) of higher plants and a C-terminal domain of histidine kinase domain( HKD). Due to their simple structure, bacteriophytochromes broaden the view of phytochrome evolution and provide us with a simple model to investigate phytochrome-mediated light signal in higher plants. In this report, the bacteriophytochromes from Synechocystis sp. PCC6803 were investigated. The gene cph1 and its fragment cph1 (C-435) were isolated from the Synechocystis sp. PCC6803 genomic DNA by polymerase chain reaction(PCR) using specific primers. Then, the genes were cloned with the vector pBluescript, yielding plasmids pBlu-cphl and pBlu-cph1 ( C-435), before they are subcloned with the vector pET30, using the EcoRV and Xho I restriction sites. pBlu-cph1, pBlu-cph1 (N-435) were cleaved with Sma I and Xho I, and the released genes were ligated to the pET30a fragment. The E. coli [strain BL21 (DE3)] cells containing recombinant pET30a were grown in medium RB at 20 degrees C, and harvested 6 h later after induction with isopropyl thio-beta-D-galactoside (IPTG). Then, reconstitution systems were employed to study the characteristics of the genes. In the reconstitution system, autoassembly of aprotein of phytochrome with PCB was investigated. The chromophore addition was an autocatalytic process. Reconstitution products were red/infrared (R/FR) photochromic, which was similar to that of the phytoehrome in higher plants. How ever, the spectral change ratios (deltaAmax/deltaAmin) of the two fragments differed from each other. It was also shown that PCB was covalently bound to apo-protein via Zn2+ fluoresc ence SDS-PAGE. After irradiation by light of 700 nm, the maximum absorption spectrum o f holo-Cphl was 650nm. The absorption of it after denaturatior in the dark with ur ea in the presence of hydrochloric acid (pH = 2) was 660nm, which was similar with th at of cis-PCB. In addition, after irradiation by light of 650nm, the maximum absorption spectrum of holo-Cph1 was 700nm. The absorption of it after denaturation in the dark with urea in the presence of hydrochloric acid (pH = 2) was 600nm, which was similar with that of trans-PCB. The result showed that the photochromism of phytochrome resulted from the isomerizaation of chromophore (PCB in this report). The reconstitution of Cph1 (C-435) under the same condition supported the conclusion. Fluorescence emission spectrum of the products suggested that bacteriophytochrom e structure with cis-PCB was more stable than that with trans-PCB. The new reconstitution system in this report sets a base for the application of phytochrome as photochromic biomaterials in biosensors. In addition, phytochrome shows great potential in food, cosmetic and biological engineering, etc.
Bacterial Proteins ; biosynthesis ; chemistry ; genetics ; Cloning, Molecular ; Escherichia coli ; genetics ; metabolism ; Gene Expression Regulation, Bacterial ; radiation effects ; Genetic Vectors ; Photochemistry ; Phytochrome ; biosynthesis ; chemistry ; genetics ; Protein Kinases ; biosynthesis ; chemistry ; genetics ; Recombinant Proteins ; biosynthesis ; chemistry ; genetics ; Synechocystis ; chemistry

Introduction to the theories on improving coordination level of the new rural cooperative medical system,including the risk theory,great number rule,fair theory,demand theory and supply theory which are cornerstones of enhancing the NRCMS improving the pooling level.The paper also probed into the practices of improving the pooling level of the NRCMS,including the models of high level,middle level and low level pooling.These theories and practices can help the localities better design and manage the pooling level of the NRCMS.

Objective To detect serum level of long noncoding RNA ( lncRNA) BC200 in gastric cancer(GC) patients, and investigate its relationship with clinical features , and evaluate its diagnostic value for GC.Methods A case-control study was performed.From November 2014 to July 2015, serum levels of lncRNA BC200 were detected by real-time quantitative polymerase chain reaction in 124 patients with GC , 41 patients with atrophic gastritis and 59 normal controls who were hospitalized in Qilu Hospital of Shandong University.Meanwhile , serum carcinoembryonic antigen ( CEA ) and carbohydrate antigen 72-4 ( CA72-4 ) were detected by electrochemical luminescence immunoassay .Serum levels of lncRNA BC200, before and 3, 7, 10, 30, 100 days after radical operation in another 31 patients with GC were determined.The sensitivity and specificity of serum lncRNA BC200, CEA and CA72-4 were analyzed by using of the receiver operating characteristic ( ROC) curve.The comparison between two groups was performed with Mann-Whitney U test and the comparison among many groups was conducted with Kruskal-Wallis H test.Results Serum levels of lncRNA BC200 in GC patients with stage Ⅰ and Ⅱ[1.041(0.794,1.462)] and stage Ⅲ and Ⅳ[1.290 (0.978,1.794)]were significantly higher than those in patients with precancerous lesion [0.969(0.699, 1.219)]and normal controls[0.801(0.556,1.599)](H =54.68,P<0.000 1).Compared with pre-operation[1.120 (0.859,1.663)], the serum BC200 levels decreased significantly in 10 days [0.903 (0.724,1.182)](U=55.0,P<0.000 1), 30 days[0.759(0.671,1.037)](U=299.0,P=0.026 1), and 100 days[0.478(0.378,0.635)](U=41.0,P<0.000 1) after surgery.The area under the receiver operating characteristics curve ( AUC) of serum lncRNA BC200 was 0.865 for GC diagnosis, which was significantly higher than that of serum CA 72-4 ( AUC =0.699 ) or CEA ( AUC =0.807 ) .The AUC of combined detection of three tests was 0.934.Conclusion Serum lncRNA BC200 levels are significantly increased in GC patients , which may be used as a potential biomarker in GC diagnosis and monitoring .