[Expression and Regulatory Mechanism of Autophagy-related Genes in Synovial Tissues of Patients with Rheumatoid Arthritis].

Objective To investigate the expression regulation of autophagy-related genes(ATG)and the mechanism of autophagy in rheumatoid arthritis(RA).Methods The differentially expressed genes(DEG)of RA were identified from GSE55235 and GSE55457,on the basis of which the differentially expressed autophagy-related genes(DE-ATG)were selected from the Human Autophagy Database.STRING 11.0 and GeneMANIA were used to establish protein-protein interaction networks.Further,the transcription factor-gene-miRNA co-expression network was established via NetworkAnalyst and Cytoscape.Finally,receiver operating characteristic(ROC)curve and DrugBank were employed to evaluate the efficacy of the predicted biomarkers and the performance of drugs targeting DE-ATG.GraphPad Prism 8.2.1 and R 4.0.3 were used for statistical analysis and graphics.Results A total of 485 DEG were enriched in signaling pathways such as T cell activation,hormone regulation,osteoclast differentiation,RA,and chemokines.Eleven DE-ATG regulated the expression of RUNX1,TP53,SOX2,and hsa-mir-155-5p in synovial tissues of RA patients and were involved in the response to environmental factors such as 2,3,7,8-tetrachlorodibenzodioxin and silicon dioxide.The ROC curve analysis identified the DE-ATG with good sensitivity and specificity,such as MYC,MAPK8,CDKN1A,and TNFSF10,which can be used to distinguish certain phenotypes and serve as novel biomarkers for RA.Conclusions In RA,down-regulated DE-ATG expression may promote apoptosis and lysis of chondrocytes.The identified novel biomarkers provides new ideas and methods for diagnosing and treating RA.The establishment of transcription factor-miRNA-gene co-expression network provides direct evidence for dissecting synovial inflammation and articular cartilage destruction.

Acupuncture for the treatment of obesity in adults: a systematic review and meta-analysis.

OBJECTIVE: Meta-analysis was used to assess the clinical efficacy of acupuncture treatment for simple obesity and to provide evidence-based medical data for treating obesity with acupuncture. METHODS: A comprehensive search of studies on MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and Chinese databases (Wan Fang,CNKI and VIP) from 1 January 1915 through 30 November 2015 (MEDLINE search updated through 31 December 2015) was performed. We included only randomised controlled trials (RCTs) that used acupuncture and sham acupuncture to treat simple obesity. The effect of acupuncture on simple obesity was measured using body mass index (BMI), body fat mass (BFM), waist circumference (WC), hip circumference (HC), and body weight (BW). The Jadad scale was used to assess methodological quality. The random effects model was used in the pooled analysis to adjust for the heterogeneity of the included studies, and funnel plots were used to examine publication bias. The differences between treatment groups were reported as mean differences (MD). RESULTS: Eleven RCTs were selected after all relevant literature from the electronic databases had been screened. There were 338 and 305 participants in the acupuncture and sham acupuncture groups, respectively. Auricular and electro acupuncture were both able to reduce BMI in obese patients (MD 0.47 kg/m2, 95% CI 0.35 to 0.58, p<0.001; MD 0.50 kg/m2, 95% CI 0.38 to 0.62, p<0.001). BFM change after acupuncture treatment compared with sham treatment was statistically significant (MD 0.66 kg, 95% CI 0.51 to 0.80, p<0.001). There were also significant differences in WC and HC between the acupuncture and sham acupuncture groups (MDwc2.02 cm, 95% CI 0.21 to 3.83, p=0.03; MDHC2.74 cm, 95% CI 1.21 to 4.27, p=0.0004). BW was not statistically significantly different between the acupuncture and sham acupuncture groups (MD 0.60 kg, 95% CI -0.20 to 1.39, p=0.14). Begg's test and funnel plots showed that the potential publication bias of the included studies was very slight (p>0.05). CONCLUSION: Acupuncture for simple obesity appeared to be an effective treatment, but more studies on the safety of acupuncture used to treat simple obesity are required.

Molecular characterization of Sp110 gene in pigs.

Speckled 110 kDa (Sp110) plays an important role in infectious diseases, as revealed by studies in humans. However, little is known regarding porcine Sp110. To elucidate its potential role in porcine resistance to viral diseases, here, the complete coding sequence of porcine Sp110 gene and its 26 alternatively spliced isoforms were isolated using reverse transcription (RT)-polymerase chain reaction (PCR), and another seven splicing patterns were obtained using a minigene construct. Subcellular distribution of 11 representative isoforms was characterized in PK-15 cells transiently transfected with their respective GFP fusion constructs, and only isoforms (R and V) bearing all functional domains were localized in nucleus, indicating all the other isoforms lose normal functions of Sp110 owing to alternative splicing. Real-time quantitative PCR and competitive RT-PCR showed that both isoforms R and V had similar tissue expression profile, half-life and response to poly(I:C), a synthetic analog of viral double-stranded RNA, while the longer one (isoform R) was transcribed at a higher level. The results indicated that porcine Sp110 has a role in viral infection and that isoform R is the dominant active form. Overall the data provide potential resource for molecular breeding of pig resistant to diseases and contributes to breeding pigs resistant to viral infection.

Inhibition of Notch Signaling Promotes the Adipogenic Differentiation of Mesenchymal Stem Cells Through Autophagy Activation and PTEN-PI3K/AKT/mTOR Pathway.

BACKGROUND: The Notch signaling pathway is implicated in a broad range of developmental processes, including cell fate decisions. This study was designed to determine the role of Notch signaling in adipogenic differentiation of human bone marrow derived MSCs (BM-MSCs). METHODS: The Notch signaling was inhibited by the γ-secretase inhibitor N-[N-(3,5-difluor- ophenacetyl-L-alanyl)]-S-phenylglycine t-butylester (DAPT). The markers involving adipogenic differentiation of MSCs, the relative pathway PTEN-PI3K/Akt/mTOR and autophagy activation were then analyzed. Furthermore, the autophagy inhibitor chloroquine (CQ) and 3-methyladenine (3-MA) were used to study the role of autophagy in the DAPT-induced the adipogenic differentiation of MSCs. RESULTS: We first confirmed the down -regulation of Notch gene expression during MSCs adipocyte differentiation, and showed that the inhibition of Notch signaling significantly enhanced adipogenic differentiation of MSCs. Furthermore, Notch inhibitor DAPT induced early autophagy by acting on PTEN-PI3K/Akt/mTOR pathway. The autophagy inhibitor CQ and 3-MA dramatically abolished the effects of DAPT-induced autophagy and adipogenic differentiation of MSCs. CONCLUSION: Our results indicate that inhibition of Notch signaling could promote MSCs adipogenesis mediated by autophagy involving PTEN-PI3K/Akt/mTOR pathway. Notch signaling could be a novel target for regulating the adipogenic differentiation of MSCs.

Cloning and identification of splice variants of the porcine PILRA gene.

Paired immunoglobulin-like type 2 receptors (PILRs) are members of the immunoglobulin superfamily and composed of two subtypes, α and ß. PILRα plays an important role in the immune response against invading pathogens, but so far there is no report on porcine PILRα. In order to analyze the potential role of PILRα in porcine disease-resistant breeding, we first cloned the PILRA gene (V1-V3, GenBank accession Nos. KJ143679-81) into pigs, and identified its three splice variants. Each variant conceptually translates into proteins of 271 amino acids (aa), 254aa and 283aa, respectively. Furthermore, quantitative real-time PCR was used to construct expression profiles of each variant in tissues and that induced by Poly(I:C). All three variants had the highest expression levels in the spleen, followed by liver and lung tissues. While levels were low or undetectable in the heart, kidney, stomach, muscle, lymph, large intestine, small intestine and bladder. Poly(I:C) significantly induced the expression of splice variant 1 (V1) of porcine PILRA, but hardly affected the expression of V2 and V3. The results lay a foundation for further study on the role of PILRA in porcine breeding and disease resistance.

The effects of venlafaxine on cortical motor area activity in healthy subjects: a pilot study.

In the study, we used functional magnetic resonance imaging associated with behavioral assessment to observe the effects of venlafaxine on the modulation of human motor cortex activation and to provide preliminary data for further assessing its influence on motor functional reorganization after stroke injury. In a randomized, double-blind, crossover study, 8 right-handed subjects received 75 mg of either venlafaxine or a placebo daily over a period of 7 days separated by 3 washout days. The volunteers were asked to execute motor tasks, which included the dynamometer and finger-tapping test. In addition, laboratory tests and functional magnetic resonance imaging examination, before the start of the experiment and after administration of placebo and venlafaxine, were performed. It was shown that the finger-tapping rate of each hand in the venlafaxine stage was significantly improved compared with that observed in the placebo stage (n = 8, F left hand = 57.69, F right hand = 184.48, P < 0.001). The changes in the recorded grip strengths of both hands were not significant between the stages (n = 8, F = 2.63, P > 0.05). In the venlafaxine stage, the activations of the contralateral primary sensorimotor cortex, contralateral premotor cortex, and contralateral supplementary motor area were enhanced significantly, whereas the activation of the bilateral parietal cortices was decreased when compared with the placebo stage. Meanwhile, the enhancement of contralateral primary sensorimotor cortex activation had a positive correlation with the improvement of the finger-tapping rate. It was concluded that venlafaxine could modulate the cortical excitability and improve finger dexterity and reaction speed, which greatly related to the increase of contralateral motor cortical excitability.

[Brain mappings in non-fluent late Chinese-English bilinguals].

OBJECTIVE: To discuss the distribution characteristics of language areas in Chinese-English non-fluent late bilinguals. METHODS: Six Chinese-English bilinguals with eloquent tumors underwent awake-surgeries. The activated areas of BOLD-fMRI were obtained as the patients performed pure naming, verb generation, and abstract/concrete judgment tasks. Direct cortical stimulation(DCS) as the golden standard of language mapping were performed during awake-surgeries on the exposed cortical areas. BOLD-fMRI results of 3 language tasks were compared with DCS results. The statistical method was McNemer. RESULTS: Sixteen positive sites(22.5%) were comfirmed out of 71 stimulations. There were 3 specific language sites, in which 2 sites were specific English sites and 1 site was specific Chinese site. When activated areas of BOLD-fMRI were compared with the DCS results, verb generation task had the highest concordance rate 40.9% (95%CI:30.2%-52.5%) . There were significant differences between the results of BOLD-fMRI and DCS of all 3 bilingual tasks(P < 0.017). CONCLUSIONS: There are specific language areas in Chinese-English non-fluent late bilinguals. The BOLD-fMRI language mapping could not substitute DCS in the context of mapping language areas in bilinguals.

[A study on the neuronal mechanism of retrieval of long-term digital memory in human by functional magnetic resonance imaging].

To investigate the neuronal mechanism of retrieval of long-term digital memory in healthy volunteers, functional magnetic resonance imaging (fMRI) technique was used in the study. Twenty-two right-handed volunteers were subjected to a long-term digital memory test with block-design. The memory task and control task were adopted in the experiment alternatively. The fMRI data were recorded by a Siemens 1.5T MR machine and analyzed by SPM99. The activated brain regions were shown in the Talairach coordinate. The results showed that the Brodmann's area (BA) 9 region in left middle frontal gyrus was the most activated cortex during the long-term digital memory task. The left medial frontal gyrus, left inferior frontal gyrus, right inferior frontal gyrus, cingulate gyrus, left inferior parietal lobule, left superior parietal lobule, right superior parietal lobule, right middle temporal gyrus, left lingual gyrus, left middle occipital gyrus, right middle brain, cerebellum and right caudate nucleus tail were also involved. The activation in cortices showed obvious left predominance. It is suggested that a series of brain regions with left predominance are involved in long-term digital memory. Left lateral frontal cortex would be the most important structure for information extraction, while the other cortices and their connections may be important for processing and long-term storage of digital information.

Speckled 100 kDa gene in pigs: Alternative splicing, subcellular localization, and response to interferon-α stimulation.

Speckled 100 kDa (Sp100) plays an important role in the antiviral immune response, however, little is known about porcine Sp100. In this study, porcine Sp100 was cloned and its response to interferon (IFN) α was identified. We obtained the cDNA (V1) of the gene, SP100, and seven alternative splicing variants (V2-8). Isoform V1 encoded a 386 amino acid protein and contained a homogeneously-staining region (HSR) domain. Isoforms V3, 4, 6 and 7 were deletion/insertion variants and contained HSR domain as V1. The splicing of porcine SP100 was very complicated and many transcripts existed as revealed by cloning and minigene analyses. Using GFP-fusion constructs isoforms V1, 3, 4, 6 and 7 were localized to nucleus and the nuclear localization signal was identified as PSNRKRR at positions 331-337 of V1. Porcine SP100 was unevenly distributed in all tissues studied and differentially expressed between pigs with different disease-resistance/susceptibilities. Porcine SP100 was strongly increased by IFNα due to the existence of an IFN-stimulated response element in the promoter. A single nucleotide - 70A > C polymorphism enhanced promoter activity. The results provided the basis for determining the role of Sp100 in antiviral responses and may assist in breeding pigs with high disease-resistance.

Epidemiological characteristics of measles from 2000 to 2014: Results of a measles catch-up vaccination campaign in Xianyang, China.

This study was a cross-sectional case-control study aimed at (1) identifying risk factors contributing to the measles epidemic and (2) evaluating the impacts of measles-containing vaccines (MCVs), with the goal of providing evidence-based recommendations for measles elimination strategies in China. Data on measles cases from 2000 to 2014 were obtained from a passive surveillance system at the Center for Diseases Prevention and Control in Xianyang. The effectiveness of MCVs was evaluated in 357 patients with a vaccination history and 503 healthy randomly selected controls. Patient data were subjected to multivariable logistic regression modeling. From 2005 to 2014, the average incidence of measles in Xianyang was 5.42 cases per 100,000 people. The second MCV dose was highly protective in 8-month-old infants. MCVs in general have been highly protective in 8-month-old infants. Multivariable logistic regression modeling indicated that age (≥2 years vs. <2years), MCV dose 2 vaccination, and MV vaccination were each independently associated with measles case status. In conclusions: A MCV should be administered on time to all age-eligible children, reproductive-age women, and migrant populations, to maximize herd immunity to measles.

Brain cancer surgery in the language areas of Mandarin-Cantonese bilinguals.

OBJECTIVE: This study aimed to study methods for protecting the language areas during tumor surgery in Mandarin-Cantonese bilinguals (MCBs). MATERIALS AND METHODS: Eleven MCB patients were positioned for awake surgery with the purpose of preserving both of their language proficiencies. All the exposed cortices were electrically stimulated 1 cm x 1 cm with anelectrode, and all the positive sites of stimulation were recorded for analyses, the tumor resection point was limited by 1cm distant from the language areas identified by electrical stimulation. RESULTS: All patients had at least one language area identified; a total of 154 points were stimulated, with 22 positive points (14.3%), including five specific language areas, which all resulted in simple anomiain either language when stimulated. Among these, three were specific to Mandarin (1.9%), whereas two were specific to Cantonese (1.3%). CONCLUSIONS: In proficient MBCs, areas specific to each language exist. Thus, performing intraoperative bilingual tasks to locate these language areas is necessary in order to preserve language function.

The modulation of venlafaxine on cortical activation of language area in healthy subjects with fMRI study.

RATIONALE: Previous studies have shown that selective serotonin reuptake inhibitors, activators of the cortex, apparently improved language functional recovery after brain damage rather than simply affective disorders. OBJECTIVE: Our aim was to determine whether venlafaxine (an agonist of both norepinephrine and 5-hydroxytryptamine) could modulate language cortex function. METHODS: A double-blind, crossover, randomized design was used to compare two 7-day treatment sessions with either venlafaxine (75 mg per day) or placebo. A functional magnetic resonance imaging experiment and two language function tests were performed on eight healthy males (mean age, 28.25 ± 3.15 years) at the end of each session, i.e., study entry, after venlafaxine, and after placebo (days 0, 7, and 18). Hyperactivation (venlafaxine minus placebo >0) or hypoactivation (placebo minus venlafaxine >0) by venlaxafine was assessed on the basis of the activation-baseline contrast. RESULTS: The naming score (P < .001) and spontaneous language fluency (P < .001) were significantly higher after venlafaxine than after placebo. Functional magnetic resonance imaging (fMRI) showed that (1) picture naming activated the left posterior gyrus frontalis medius and the bilateral fusiform gyrus and the bilateral outer occipital lobes, (2) hyperactivation was observed in the adjoining area of posterior upper Broca area and premotor area in the dominant hemisphere in venlafaxine session (after venlafaxine), (3) the hyperactivation of the left gyrus frontalis medius on fMRI and the increase in naming test score were positively correlated, and (4) by contrast, we observed hypoactivation in the temporo-parieto-occipital region in venlafaxine session (after venlafaxine). This improvement may be related to increased phonics-related output in the frontal language cortex of the dominant hemisphere.