Objective: To examine the causal relationship between body mass index (BMI) and 25 types of autoimmune diseases (ADs) using Mendelian randomization (MR) study method. Methods: The genome-wide association study (GWAS) data for BMI and 25 types of ADs were obtained from IEU OPEN GWAS database. Single nucleotide polymorphisms (SNPs) related to BMI were used as instrumental variables, 25 types of ADs were used as study outcomes, and MR analysis was performed using inverse variance weighted (IVW) method. Heterogeneity was evaluated using Cochran's Q test, horizontal pleiotropy was tested using MR-Egger regression and MR-PRESSO, and results robustness was verified with leave-one-out method. Results: Cochran's Q test showed heterogeneity of MR analysis results (P<0.05), and a random effect model was employed. The results of MR analysis showed that elevated BMI increased the incidence risks of type 1 diabetes mellitus (OR=1.519, 95%CI: 1.281-1.801), IgA nephropathy (OR=1.227, 95%CI: 1.134-1.327), adult Still disease (OR=1.002, 95%CI: 1.001-1.003), multiple sclerosis (OR=1.303, 95%CI: 1.115-1.523), narcolepsy (OR=1.029, 95%CI: 1.017-1.040), Hashimoto thyroiditis (OR=1.561, 95%CI: 1.391-1.751), autoimmune hepatitis (OR=1.481, 95%CI: 1.076-2.038), rheumatoid arthritis (OR=1.209, 95%CI: 1.054-1.386), psoriasis vulgaris (OR=1.719, 95%CI: 1.427-2.070) and pernicious anemia (OR=1.001, 95%CI: 1.000-1.002). No causal relationship was found with other ADs (all P>0.05). MR-Egger regression identified no horizontal pleiotropy of instrumental variables (all P>0.05), while MR-PRESSO test identified partial horizontal pleiotropy (all P<0.05), which remained consistent with the original results after adjustment (P>0.05). Leave-one-out analysis showed results robustness. Conclusion There are causal relationship among BMI and type 1 diabetes mellitus, IgA nephropathy, adult Still disease, multiple sclerosis, narcolepsy, Hashimoto thyroiditis, autoimmune hepatitis, rheumatoid arthritis, psoriasis vulgaris and pernicious anemia.

[Objective] To describe a case of a rare,novel mutation causing recurrent chorioamniotic membrane separation in a Chinese family with combined next-generation sequencing (NGS) and Sanger sequencing.[Methods] For the affected fetus,potential mutation were detected by the conbinedcombined next-generation sequencing (NGS) and Sanger sequencing.And the prenatal diagnosis were identified by Sanger sequencing.[Results] A frameshifting mutation c.1389_1390delAG (inherited from mother),and a missense mutationc.1006 G ＞ C (inherited from mother) have been identified in the affected fetus (the second pregnancy).The prenatal diagnosis of the third fetus turns out to be a carrier,the mutation was inherited from father.[Conclusions] We describe a novel mutation in gene ZMPSTE24,which was considered with mandibuloacral dysplasia with type B,and that may be the cousecoursecausing of recurrent chorioamniotic membrane separation.This rare mutation constitutes an additional heterogeneous defect causing chorioamniotic membrane separation.And the conbinedcombined next-generation sequencing (NGS) and Sanger sequencing allows high resolution characterization of novel mutions that are not readily detected by present methods.

In order to develop a more effective drug for dry eye disease, the preparation of lifitegrast eye drops was carried out, and the safety and efficacy of lifitegrast eye drops in vitro and in vivo were investigated. First the method for the determination of lifitegrast content was established, and then the composition and preparation process of the preparation were determined by literature review and single factor experiment. Finally, the safety of lifitegrast eye drops was evaluated by Draize eye irritation test and HE staining, and the therapeutic efficacy was evaluated by Schirmer test and ELISA test. The results showed that the final prescription of lifitegrast eye drops consisted of 5% lifitegrast, 0.4% sodium chloride, 0.3%−0.4% anhydrous disodium hydrogen phosphate, 0.3% sodium thiosulfate pentahydrate and 0.3% sodium hydroxide. The appearance of lifitegrast eye drops was transparent and slightly brownish yellow solution, the pH was7.75±0.05, the osmotic pressure was in the range of 200−330 mOsmol/kg and it had good stability at 60℃ for 3 months. There was no significant difference in irritation study compared with normal saline. Schirmer test showed that tear secretion was increased and the expression of inflammatory factors IL-6, IL-1β and TNF-α in tears were significantly decreased after treatment with lifitegrast eye drops and compared to the commercially available emulsion cyclosporine eye drops, it takes effect faster. The above results indicate that lifitegrast eye drops are simple to prepare and stable, which is a better choice for the rapid treatment of dry eye disease.

OBJECTIVETo investigate the effect of environmental risk factors on the development of stroke.

METHODSWith the use of cold-stimuli plus high-salt intake as environmental risk factors, a hypertension model with the complication of stroke was established in rats, then, a new technique, suppression subtractive hybridization (SSH), was used to identify the differential genes which specifically expressed in total cerebrum tissue of rat in each group. Comparison was made between control group and stroke group.

RESULTSBy the application of SSH, a total of 576 clones were generated in this study from two subtractive libraries, among them 456 clones were usable and were analyzed. Genes for cell/organs defense were down-regulated in stroke group and metabolism transcripts were shown to be up-regulated (P<0.01).

CONCLUSIONCell/organs defense genes may play important roles in the development of stroke. The above findings suggested that environmental risk factors could genetically alter individual sensitivity to stroke.

Animals ; Brain ; metabolism ; pathology ; Cell Division ; genetics ; Cold Temperature ; DNA, Complementary ; chemistry ; genetics ; Expressed Sequence Tags ; Gene Expression Regulation ; drug effects ; Immunity, Innate ; genetics ; Male ; RNA, Messenger ; drug effects ; genetics ; metabolism ; Rats ; Rats, Wistar ; Sequence Analysis, DNA ; Signal Transduction ; genetics ; Sodium Chloride, Dietary ; administration & dosage ; Stroke ; genetics

Objective To analyze the drug resistance phenotype and genetic background of New Delhi metallo-β-lactamase (NDM)-producing bacterial strains in Lishui area of Zhejiang province.Methods The imipenem-resistant Enterobacteriaceae strains were isolated from January 2012 to December 2016 in Lishui Municipal Central Hospital of Zhejiang Province.Mrieux Vitek 2 Compact system was used to identified strains and PCR was used to screen for blaNDMgene.Susceptibility was detected by K-B method and MICs were obtained by Vitek 2 with GN13 cards.Plasmids typing was carried out by DNA sequencing of the replication initiator with the transconjugates as templates.The blaNDMgenetic contexts were detected by PCR and complete genome sequencing.Results A total of 102 strains of carbapenem-resistant enterobacteria (CRE), mainly Escherichia coli and Enterobacter cloacae, were isolated, of which 15 were positive for blaNDMwith a positive detection rate of 14.7%.The resistance rate to β-lactam antibiotics was 100%, and the resistance rates to aztreonam, compound sulfamethoxazole , tobramycin and gentamicin were all ＞80%;and the resistance rate to quinolones was ＞50%.Among the 15 NDM-producing strains , 12 strains were positive for Hodge test, and 2 strains of Enterobacter cloacae and 1 strain of Escherichia coli were negative. There were 11 strains of blaNDM-1and 4 strains of blaNDM-1.A variety of plasmid types such as IncX 3, IncFIIγ and IncA/C were detected, and 4 blaNDM-5genes were located in the IncX3 plasmid.Four blaNDMsurrounding gene structures were found, of which 8 blaNDM-1genes were located in ISAb125-hyp-blaNDM-1-bleMBL-TrpF-DsbC-IS26, while blaNDM-5was located in IS3000-IS5-blaNDM-5-bleMBL-TrpF-DsbC-IS26 structure, and the former was reported for the first time in China.Conclusion NDM-producing bacterial strains in Lishui area are prevalent at a low level and have high sensitivity to fosfomycin and polymyxin .The blaNDMgene may have multiple sources, but IncX3 plasmid is still the main source for gene transfer.Some new types of blaNDM-1 gene structure have been also found in this study.

OBJECTIVETo explore the effects on cell proliferation and invasion as well as molecular basis after suppressing EZH2 expression in endometrial carcinoma cells by using siRNAs.

METHODSRT-PCR was used to examine the expression of EZH2 in endometrial carcinoma and their paracancerous tissues. SiRNAs targeting to EZH2 were transfected to endometrial carcinoma cells, and MTT, FACS, and boyden assays were utilized to examine cell proliferation, cell cycle change, and cell invasion. Finally, the molecular mechanisms of EZH2 on cell function alteration were investigated.

RESULTSCompared with paracancerous tissues, increased expression trend of EZH2 mRNA was showed in endometrial carcinoma tissues. Further, knocking down EZH2 expression inhibited cell growth, cell cycle transition from G1 to S phase, and cell invasion ability. Molecular basis indicated that suppression of EZH2 downregulated the expression of E2F1 and MMP9 and upregulated tumor suppressor p21 expression.

CONCLUSIONEZH2 expression is increased in endometrial carcinoma tissues. Knocking down EZH2 expression suppresses the cell growth, cell cycle transition and cell invasion by downregulated E2F1 and MMP9, and upregulated tumor suppressor p21 expression.

Cell Line, Tumor ; Cell Proliferation ; E2F1 Transcription Factor ; metabolism ; Endometrial Neoplasms ; genetics ; pathology ; Enhancer of Zeste Homolog 2 Protein ; Female ; Genes, Tumor Suppressor ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; Polycomb Repressive Complex 2 ; genetics ; RNA Interference ; RNA, Messenger ; genetics ; RNA, Small Interfering ; Transfection

BACKGROUND:The second heart field is crucial for the development of the embryonic heart.Abnormal development of the second heart field can result in multiple cardiac malformations.After Cx43 gene knockout,reduced formation and proliferation of cells of the second heart field can be observed,but the specific reason remains unclear. OBJECTIVE:(1)To determine whether β-catenin,Smo and Cx43 were co-expressed in the second heart field and the endoderm,we observed the expression patterns of these proteins.(2)To explore whether Cx43 interacts with the Wnt/β-catenin pathway or the Shh pathway in the development of the second heart field. METHODS:Serial paraffin sections of the mouse embryos at embryonic days 10-12 were selected for immunohistochemical staining,hematoxylin-eosin staining and immunofluorescence staining.The primitive gut of mouse embryos at embryonic day 11 was separated for western blot assay and co-immunoprecipitation. RESULTS AND CONCLUSION:(1)Cx43 and Isl1 were co-expressed in some mesenchymal cells on the ventral side of the foregut and dorsal wall of the pericardial cavity of mouse embryos at embryonic days 10-12;Isl1 positive cells increased while Cx43 positive cells increased.(2)Cx43 and β-catenin were co-expressed in the ventral part of the endoderm at embryonic days 10-12.(3)Cx43 and Smo were co-expressed in the endoderm at embryonic days 10-12.(4)The co-immunoprecipitation results confirmed that there was an interaction between Cx43 and β-catenin,which suggested that Cx43 interacted with β-catenin to participate in the development of the second heart field.

A patient with thymoma associated immunodeficiency syndrome (Good's syndrome) and bronchiectasis was retrospectively analyzed. Good's syndrome is a rare condition of immunodeficiency that is characterized by thymoma and hypogammaglobulinemia. It is important to bear in mind that Good's syndrome should be included in the differential diagnosis When patients repeatedly visited for bronchiectasis or infection, we should alert to their immune state and history of thymoma. Early screening of immunological status and aggressive correction of immune deficiency are beneficial to improving the prognosis to patients with Good's syndrome.
Agammaglobulinemia/complications* ; Bronchiectasis/complications* ; Humans ; Retrospective Studies ; Thymoma/complications* ; Thymus Neoplasms/complications*