Objective:To investigate the effect of astragaloside Ⅳ on the apoptosis of thyroid cells in Hashimoto's thyroiditis(HT)rats and Ras homolog gene family member A(RhoA)/Rho-associated coiled-coil containing kinase 2(ROCK2)pathway.Methods:The HT rat model was induced by subcutaneous injection of thyroglobulin combined with high iodine drinking water and randomly divided into model group,astragaloside(80 mg/kg)group,Rhosin(RhoA inhibitor,40 mg/kg)group,astragaloside Ⅳ(80 mg/kg)+ Rhosin(40 mg/kg)group(12 rats in each group),another 12 SD rats were selected and drank water normally and injected the same dose of saline subcutaneously as control group.After the drugs were grouped and processed,the serum anti-thyroglobulin antibody(TGAb),anti-thyroid peroxidase antibody(TPOAb)levels and the inflammatory factors IL-6,IL-17,IL-1β contents were measured by ELISA kits;the pathological changes of thyroid tissue in each group were detected by hematoxylin-eosin(HE)staining;the apopto-sis rate of rat thyroid cells in each group were detected by TUNEL staining;the expressions of RhoA/ROCK2 pathway proteins in thy-roid tissues of rats in each group were detected by Western blot.Results:Compared with the control group,the thyroid follicles in the model group had abnormal structure,some atrophy or disappearance,disordered arrangement,surrounding inflammatory cell infiltra-tion,and obvious pathological damage to the thyroid tissue,the serum TGAb,TPOAb,IL-6,IL-17 and IL-1β levels,thyroid cell apoptosis rate,and thyroid tissue RhoA and ROCK2 protein expression levels were significantly increased(P<0.05);compared with model group,the pathological damage of the thyroid tissue of rats in the drug intervention group were reduced,the serum TGAb,TPOAb,IL-6,IL-17 and IL-1β levels,thyroid cell apoptosis rate,and thyroid tissue RhoA and ROCK2 protein expression levels were decreased(P<0.05);compared with astragaloside Ⅳ group and the Rhosin group respectively,the pathological damage of the thyroid tissue of rats in the astragaloside Ⅳ+Rhosin group were further reduced,the serum TGAb,TPOAb,IL-6,IL-17 and IL-1β levels,thyroid cell apoptosis rate,thyroid tissue RhoA and ROCK2 protein expression levels were decreased(P<0.05).Conclusion:Astragaloside Ⅳ may down-regulate the expression of RhoA/ROCK2 pathway to reduce the inflammatory injury of thyroid tissue,inhib-it thyroid cell apoptosis,and improve the symptoms of HT in rats.

Objective: To study the association of single nucleotide polymorphism (SNP)276 in adiponectin gene with essential hypertension in population with impaired glucose regulation in Han people of Shanxi region. Methods: The study population consisted of 216 Chinese Hans residents with impaired glucose regulation (IGR) in Shanxi province. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to test the adiponectin SNP276G/T polymorphism. Results: The distributions of genotypes and alleles of SNP276 both displayed significant difference between the IGR complicating norm tension group and the hypertension group (P=0.025, P=0.007). Compared with the TT genotype, the SNP276 non-TT (GT+ GG) genotype was associated with increased risk of complicating with hypertension (OR=3.346, 95% CI: 1.115-8.986, P=0.037), while after age- , sex- and BMI-adjusted, there was no significant difference between the 2 groups (P=0.349). Conclusions SNP276 in adipose most abundant gene transcript 1 (APM1) was associated with the susceptibility to be complicating essential hypertension in population with impaired glucose regulation in Han people of Shanxi region.

Virus infection induces the production of type I interferons (IFNs). IFNs bind to their heterodimeric receptors to initiate downstream cascade of signaling, leading to the up-regulation of interferon-stimulated genes (ISGs). ISGs play very important roles in innate immunity through a variety of mechanisms. Although hundreds of ISGs have been identified, it is commonly recognized that more ISGs await to be discovered. The aim of this study was to identify new ISGs and to probe their roles in regulating virus-induced type I IFN production. We used consensus interferon (Con-IFN), an artificial alpha IFN that was shown to be more potent than naturally existing type I IFN, to treat three human immune cell lines, CEM, U937 and Daudi cells. Microarray analysis was employed to identify those genes whose expressions were up-regulated. Six hundred and seventeen genes were up-regulated more than 3-fold. Out of these 617 genes, 138 were not previously reported as ISGs and thus were further pursued. Validation of these 138 genes using quantitative reverse transcription PCR (qRT-PCR) confirmed 91 genes. We screened 89 genes for those involved in Sendai virus (SeV)-induced IFN-β promoter activation, and PIM1 was identified as one whose expression inhibited SeV-mediated IFN-β activation. We provide evidence indicating that PIM1 specifically inhibits RIG-I- and MDA5-mediated IFN-β signaling. Our results expand the ISG library and identify PIM1 as an ISG that participates in the regulation of virus-induced type I interferon production.
Cells, Cultured ; Gene Library ; Humans ; Interferon Type I ; metabolism ; Interferon-beta ; genetics ; metabolism ; Proto-Oncogene Proteins c-pim-1 ; genetics ; Up-Regulation

Objective To investigate the clinicopathological features and correlation between synchronous multiple early gastric cancer (SMEGC)and single early gastric cancer (EGC).Methods From January 2008 to December 2016,the clinical data of 994 patients with EGC who underwent open or laparoscopic gastrectomy surgery were collected from the electronic medical data base of the First Affiliated Hospital of Nanjing Medical University and Xuzhou No.1 People's Hospital.The data of patients including gender,age,tumor morphologys,tumor location,tumor size,histological type,depth of invasion,lymph nodes metastasis,lymphovascular metastasis,peripheral nerve invasion,and blood types were analyzed.T test and Chi square test were used for statistical analysis.Results Among 994 EGC patients,27 cases (2.7％) were SMEGC,and 967 cases (97.3％) were single EGC.The percentage of male and female of single EGC were 71.4％ (690/967) and 28.6％ (277/967),respectively;the percentage of male and female of SMEGC were 88.9％ (24/27) and 11.1％ (3/27),respectively,and there was statistically significant difference in the gender composition ratio between single EGC and SMEGC (x2 =3.975,P=0.046).The incidence of ulcer in single EGC and SMEGC were 50.6％ (489/ 967) and 29.6 ％ (8/27),respectively,and the difference in the incidence of ulcers between single EGC and SMEGC was statistically significant (x2 =4.653,P=0.031).There were no statistically significant differences between single EGC and SMEGC in gross morphology,depth of invasion,lymph nodes metastasis,lymphovascular metastasis,peripheral nerve invasion,tumor location,pathological type and blood types (all P＞0.05).In the SMEGC patients,the incidence of main lesions invading the mucosa was 48.1％ (13/27) and submucosa invasion was 51.9％ (14/27);and for minor lesions,the corresponding incidences were 77.8％ (21/27) and 22.2％ (6/27),respectively,and the difference was statistically significant (x2 =5.063,P＜0.05).There were no statistically significant differences between the main lesions and minor lesions in tumor size,pathological type,with or without ulcers,gross morphology and tumor location (all P＞0.05).Conclusions The main risk factors of SMEGC are male and no ulcerative lesions.The clinicopathological features are similar between main lesions and minor lesions in SMEGC.

Objective To investigate the value of three-dimension (3D) ultrasound in identification of benign or malignant gastric ulceration. Methods A total of 88 patients with gastric ulcer were collected in Tianjin Nankai Hospital from March 2014 to May 2015, including 36 malignant cases and 52 benign cases confirmed by pathological results. Results of 2D ultrasound, 3D ultrasound and gastroscope diagnosis were compared, and the diagnostic values of the three methods were evaluated by the gold standard of pathologic results. Receiver operating characteristic (ROC) curves were plotted for the main measurement indicators (ulcer surface width, ulcer surface depth and thickness of stomach wall) of 3D ultrasound. The best cut-off value was determined. Results The positive rate of malignant gastric ulcer diagnosed by 3D ultrasound was significantly higher than that of 2D ultrasound (P=0.002), but there was no significant difference between 3D ultrasound and gastroscope detection (P=0.453). The diagnostic sensitivities of malignant gastric ulcer were 86.11%, 58.33%and 91.67%for 3D ultrasound, 2D ultrasound and gastroscope detection respectively. The diagnostic specificities were 100%, 100%and 96.15% respectively. The areas under the ROC curves measured by 3D ultrasound were 0.750, 0.940 and 0.977 for ulcer surface width, ulcer surface depth and thickness of stomach wall. And the best cut-off values of the three indicators were 16.55 mm, 8.05 mm and 9.90 mm. Conclusion The 3D ultrasound can show the form and structure of gastric ulcer more clearly and intuitively, which is valuable for the differential diagnosis of benign gastric ulcer and malignant gastric ulcer, and may be used for screening malignant gastric ulcer.

MicroRNAs (miRNAs) recruit the RNA-induced silencing complex (RISC) to repress the translation of target mRNAs. While the 5' 7-methylguanosine cap of target mRNAs has been well known to be important for miRNA repression, the underlying mechanism is not clear. Here we show that TNRC6A interacts with eIF4E2, a homologue of eIF4E that can bind to the cap but cannot interact with eIF4G to initiate translation, to inhibit the translation of target mRNAs. Downregulation of eIF4E2 relieved miRNA repression of reporter expression. Moreover, eIF4E2 downregulation increased the protein levels of endogenous IMP1, PTEN and PDCD4, whose expression are repressed by endogenous miRNAs. We further provide evidence showing that miRNA enhances eIF4E2 association with the target mRNA. We propose that miRNAs recruit eIF4E2 to compete with eIF4E to repress mRNA translation.
Autoantigens ; metabolism ; Cell Line ; Eukaryotic Initiation Factor-4E ; metabolism ; Gene Silencing ; Humans ; MicroRNAs ; genetics ; Protein Transport ; RNA, Messenger ; biosynthesis ; genetics ; RNA-Binding Proteins ; metabolism

Objective To study the changes and the role of MCP -1,IL -8,VEGF,NO,NOS in the T2DM patients with different types of CHD.Methods According to the result of coronary arteriongraphy and clinical symp-toms,and the diagnostic code of T2DM established by Chinese Medical Association diabetology branch in 2007, 126 patients of T2DMwith CHD were chosen and divided into two groups:ACS +T2DM group (A group,74 cases) and SAP +T2DMgroup (B group,52 cases),in addition,50 healthy people were chosen as control group.The levels of MCP -1,IL -8,VEGF were measured by the method of ELISA.The level of NO was measured by the method of nitrate reductase and NOS activity was measured by the method of spectrophotometer.Then,the results were analyzed. Results The levels of MCP -1 and IL -8 in A group and B group were[(115.98 ±39.57)pg/mL,(98.76 ± 31.55)pg/mL],[(131.22 ±42.83)pg/mL,(115.75 ±40.37)pg/mL],which were all higher than those in group C [(75.63 ±23.69)pg/mL,(68.53 ±37.85)pg/mL,t =4.12,2.26,3.78,2.21,all P <0.05)],but the VEGF [(167.87 ±54.98)pg/mL,(128.38 ±36.99)pg/mL)],NO[(46.89 ±12.92)μmol/L,(51.66 ±12.49)μmol/L)]and NOS [(39.04 ±5.19)U /mL,(40.56 ±7.03)U /mL)]were lower than those in C group [(90.21 ± 32.06)pg/mL,(64.05 ±13.58)μmol/L,(47.82 ±5.93)U /mL;t =3.05,3.17,2.43,2.79,2.49,2.25,all P <0.05].The MCP -1,IL -8 levels in A group were higher than those in B group(t =3.13,2.89,all P <0.05),but the level of VEGF and NO were lower than that in B group(t =3.04,2.95,all P <0.05),NOS in A group was lower than that in B group,but there was no statistically significant difference between the two groups(t =1.06,P >0.05). MCP -1 was positively correlated with Il -8,VEGF (r =0.35,0.33,all P <0.01),and it had negative correlation with NO (r =-0.24,P <0.05).Conclusion Inflammatory factor and oxidative stress both participate in the T2DM with different types of CHD,it relates with the degree of CHD.

The host takes use of pattern recognition receptors (PRRs) to defend against pathogen invasion or cellular damage. Among microorganism-associated molecular patterns detected by host PRRs, nucleic acids derived from bacteria or viruses are tightly supervised, providing a fundamental mechanism of host defense. Pathogenic DNAs are supposed to be detected by DNA sensors that induce the activation of NFκB or TBK1-IRF3 pathway. DNA sensor cGAS is widely expressed in innate immune cells and is a key sensor of invading DNAs in several cell types. cGAS binds to DNA, followed by a conformational change that allows the synthesis of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from adenosine triphosphate and guanosine triphosphate. cGAMP is a strong activator of STING that can activate IRF3 and subsequent type I interferon production. Here we describe recent progresses in DNA sensors especially cGAS in the innate immune responses against pathogenic DNAs.
DNA, Bacterial ; immunology ; metabolism ; DNA, Viral ; immunology ; metabolism ; Gene Expression Regulation ; Host-Pathogen Interactions ; Humans ; Immunity, Innate ; Interferon Regulatory Factor-3 ; genetics ; immunology ; Interferon Type I ; biosynthesis ; immunology ; Membrane Proteins ; genetics ; immunology ; Models, Molecular ; NF-kappa B ; genetics ; immunology ; Nucleotides, Cyclic ; biosynthesis ; immunology ; Nucleotidyltransferases ; genetics ; immunology ; Protein Binding ; Protein-Serine-Threonine Kinases ; genetics ; immunology ; Signal Transduction

Objective To compare the cumulative analgesic effects of electroacupuncture at Sanyinjiao (SP6), Xuanzhong (GB39) and non-acupoint in treating primary dysmenorrhea. Method By adopting a multi-centered randomized controlled study method, 501 patients recruited from Dongzhimen Hospital of Beijing University of Chinese Medicine, China-Japan Friendship Hospital, Beijing Hospital of Traditional Chinese Medicine of Capital Medical University, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Huguosi Hospital of Chinese Medicine of Beijing University of Chinese Medicine and the Outpatient of Shandong University of Traditional Chinese Medicine were randomized into a Sanyinjiao group, a Xuanzhong group, and a non-acupoint group, 167 subjects in each group. The electroacupuncture intervention was applied when dysmenorrhea flared up and the Visual Analogue Scale (VAS) ≥40 mm, with frequency at 2/100 Hz and intensity during patient’s endurance, 30 min each time, once a day, and for successive 3 d. Before the first treatment, 30 min after the first treatment, and respectively prior to the second and third treatment, VAS was used to measure the pain intensity. Meanwhile, the Retrospective Symptom Scale (RSS-COX 2) was investigated before the first treatment, right after the removal of needles for the first treatment, before the second and third treatment. Result The decrease of VAS in Sanyinjiao group was more significant than that in Xuanzhong group and non-acupoint group (MD=﹣2.92 mm, P=0.028; MD=﹣3.47 mm, P=0.009), while there was no significant difference between Xuanzhong group and non-acupoint group (MD=﹣0.56 mm, P=0.674); there were no significant differences in comparing the RSS-COX2 total score among the three groups (P=0.086). Conclusion Sanyinjiao (SP6) can produce a more significant cumulative analgesic effect for primary dysmenorrhea patient than Xuanzhong and non-acupoint, and the effects of Xuanzhong and non-acupoit are equivalent.

HIV-1 utilizes cellular factors for efficient replication. The viral RNA is different from cellular mRNAs in many aspects, and is prone to attacks by cellular RNA quality control systems. To establish effective infection, the virus has evolved multiple mechanisms to protect its RNA. Here, we show that expression of the Y-box binding protein 1 (YB-1) enhanced the production of HIV-1. Downregulation of endogenous YB-1 in producer cells decreased viral production. YB-1 increased viral protein expression by stabilizing HIV-1 RNAs. The stem loop 2 in the HIV-1 RNA packaging signal was mapped to be the YB-1-responsive element. Taken together, these results indicate that YB-1 stabilizes HIV-1 genomic RNA and thereby enhances HIV-1 gene expression and viral production.
5' Untranslated Regions ; Chromosome Mapping ; Down-Regulation ; HEK293 Cells ; HIV-1 ; genetics ; metabolism ; Humans ; Inverted Repeat Sequences ; Protein Binding ; RNA Interference ; RNA, Small Interfering ; metabolism ; RNA, Viral ; metabolism ; Virus Replication ; Y-Box-Binding Protein 1 ; antagonists & inhibitors ; genetics ; metabolism