Objective To determine the pathogen of a local dengue fever outbreak in Shenzhen city in 2010,and to analyze the molecular characteristics of the epidemic dengue virus strain as well as explore the possible origin.Methods The serum samples collected from the suspect dengue fever cases were detected for IgM, IgG by enzyme-linked immunosorbent assay ( ELISA ),immunochromatography and dengue virus nucleic acid by real-time polymerase chain reaction (PCR).Serum samples from patients with early stage dengue fever were used to isolate virus with C6/36 and BHK-21 cell lines.The type of isolated virus strain was determined by RT-semi-nested-PCR and realtime PCR.E gene of isolated virus strain was amplified by RT-PCR and sequenced.Homology and phylogenetic tree of E gene of Shenzhen dengue virus with the strains isolated from other areas were constructed.Results IgM,IgG and RNA of type 1 dengue virus were detected in serum samples from dengue fever suspected patients.Type 1 dengue virus named DEV1-SZ1029 was successfully isolated from the serum sample.The homology of nucleotide sequence of E gene of SZ1029 strain with standard type 1 dengue virus HAWAII 45,Fj231/04,GD14/97 and GD05/99 were 94.8％,99.6％,97.7％ and 98.5 ％,respectively.The phylogenetic tree indicated that SZ1029 had the greatest similarity with the D1/Malaysia/36000/05 strain,SG(EHI)DED142808 strain and Fj231/04 strain and they lied in the same branch of the phylogenetic tree.The isolated dengue virus type 1 belonged to genetype Ⅰ with GZ/80,Taiwan87,All patients lived in a certain construction site in Shenzhen and had no recent travel history outside the area in one month before infection.Conclusions The virological,serological and molecular features all identify that the local dengue fever outbreak in Shenzhen in 2010 is caused by type 1 dengue virus and SZ1029 strain may be transferred from Southeast Asian region,and there may be a plague focus in Shenzhen.

Objectivde To explore the efficacy of i-GMS applied to the diabetes patient outside the hospital.Methods Totally 80 type 2 diabetes mellitus patients were divided into an experiment group (Group A) and a control group (Group B).Group A executed blood glucose monitoring by Glucose Management App and intelligent blood glucose meter (personal version),and Group B completed monitoring by some portable blood glucose meter.Telephone follow-up was performed once a week,and the two groups were compared on glycated albumin (GA) value 3 weeks after discharging,values of HbA1c,FPG and PG2h 3 months after,the times of blood glucose monitoring and hypoglycaemia as well as the patient satisfaction over the glucose management.Results Group A had the values of GA,HbA1c,FPG and PG2h significantly lower than those of Group B (P＜ 0.05).The times of glucose monitoring and patient satisfaction in Group A were statistically higher than those of Group B,while the incidence rate of hypoglycaemia of the former was lower than that of the latter (P＜0.05).Conclusion I-GMS proves efficient when used for glucose self monitoring and management of the type 2 diabetes mellitus patient.

BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.

Objective To investigate the prevalence and risk predictors of depressive tendency in type 2 diabetic patients with peripheral neuropathy.Methods From May 2017 to December 2017,150 diabetic patients with peripheral neuropathy and 150 diabetic patients without peripheral neuropathy in the First Affiliated Hospital of Harbin Medical University were collected.The general clinical data,including age,sex,diabetic duration,height,weight,body mass index (BMI),fasting blood glucose (FBG),fasting insulin (FINS),homeostasis modal assessment-insulin resistance index(HOMA-IR),glycated hemoglobin(HbA1c),blood lipid and blood pressure were collected.The motor nerve and sensory nerve conduction velocity of lower limbs were measured by electromyograph.Zung depression self-rating scale(SDS) was used for self-rating of depression syndrome.Results There were 46 cases(30.67％) suffered from depression(SDS ＞50) in the neuropathic group,and 25 cases(16.67％) suffered from depression in the non-neuropathic group.The incidence rate of depression in the neuropathic group was significantly higher than that in the non-neuropathic group and tended to be severe (x2 =12.732,P =0.005).Non-conditional Logistic multivariate stepwise regression analysis showed that sex,the course of diabetes and low density lipoprotein (LDL) were associated with depressive tendency (x2 =3.994,P =0.049;x2 =5.334,P =0.032;x2 =6.172,P =0.020).Conclusion The prevalence of depression in diabetic patients with peripheral neuropathy is higher and tends to be severe.Sex,the course of diabetes and LDL are risk factors of depressive tendency.

Proteins usually associate with other molecules physically to execute their functions. Identifying these interactions is important for the functional analysis of proteins. Previously, we reported the parallel analysis of translated ORFs (PLATO) to couple ribosome display of full-length ORFs with affinity enrichment of mRNA/protein/ribosome complexes for the "bait" molecules, followed by the deep sequencing analysis of mRNA. However, the sample processing, from extraction of precipitated mRNA to generation of DNA libraries, includes numerous steps, which is tedious and may cause the loss of materials. Barcoded PLATO (PLATO-BC), an improved platform was further developed to test its application for protein interaction discovery. In this report, we tested the antisera-antigen interaction using serum samples from patients with inclusion body myositis (IBM). Tripartite motif containing 21 (TRIM21) was identified as a potentially new IBM autoantigen. We also expanded the application of PLATO-BC to identify protein interactions for JQ1, single ubiquitin peptide, and NS5 protein of Zika virus. From PLATO-BC analyses, we identified new protein interactions for these "bait" molecules. We demonstrate that Ewing sarcoma breakpoint region 1 (EWSR1) binds to JQ1 and their interactions may interrupt the EWSR1 association with acetylated histone H4. RIO kinase 3 (RIOK3), a newly identified ubiquitin-binding protein, is preferentially associated with K63-ubiquitin chain. We also find that Zika NS5 protein interacts with two previously unreported host proteins, par-3 family cell polarity regulator (PARD3) and chromosome 19 open reading frame 53 (C19orf53), whose attenuated expression benefits the replication of Zika virus. These results further demonstrate that PLATO-BC is capable of identifying novel protein interactions for various types of "bait" molecules.

The mammalian epididymis not only plays a fundamental role in the maturation of spermatozoa, but also provides protection against various stressors. The foremost among these is the threat posed by oxidative stress, which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids, proteins, and nucleic acids. In mice, the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5 (GPX5) as a major luminal scavenger in the proximal caput epididymidal segment. Accordingly, the loss of GPX5-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx5

The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC