Efficacy of single-session transcranial direct current stimulation on addiction-related inhibitory control and craving: a randomized trial in males with Internet gaming disorder.

BACKGROUND: Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (dlPFC) may reduce substance use and other addictive behaviours. However, the cognitive mechanisms that underpin such effects remain unclear. Impaired inhibitory control linked to hypoactivation of the prefrontal cortex may allow craving-related motivations to lead to compulsive addictive behaviours. However, very few studies have examined whether increasing the activation of the dlPFC via anodal tDCS could enhance inhibitory control over addiction-related distractors. The current study aimed to enrich empirical evidence related to this issue. METHODS: Thirty-three males with Internet gaming disorder underwent active (1.5 mA for 20 minutes) and sham tDCS 1 week apart, in randomized order. We assessed inhibitory control over gaming-related distractors and craving pre- and post-stimulation. RESULTS: Relative to sham treatment, active tDCS reduced interference from gaming-related (versus non-gaming) distractors and attenuated background craving, but did not affect cue-induced craving. LIMITATIONS: This study was limited by its relatively small sample size and the fact that it lacked assessments of tDCS effects on addictive behaviour. Future tDCS studies with multiple sessions in larger samples are warranted to examine the effects on addictive behaviours of alterations in addiction-related inhibitory control. CONCLUSION: These findings demonstrate that stimulation of the dlPFC influences inhibitory control over addiction-related cues and addiction-related motivation. This is the first empirical study to suggest that enhanced inhibitory control may be a cognitive mechanism underlying the effects of tDCS on addictions like Internet gaming disorder. Our finding of attenuated background craving replicated previous tDCS studies. Intriguingly, our finding of distinct tDCS effects on 2 forms of craving suggests that they may have disparate underlying mechanisms or differential sensitivity to tDCS. CLINICAL TRIALS #: NCT03352973.

A role for the right dorsolateral prefrontal cortex in enhancing regulation of both craving and negative emotions in internet gaming disorder: A randomized trial.

Reward-seeking and relief from negative emotions are two central motivational drives underlying addictions. Impaired executive control over craving and negative emotions contributes to compulsive addictive behaviors. Neuroimaging evidence has implicated the prefrontal cortex (PFC) in regulating craving or emotions. This study aims at examining whether anodal transcranial direct current stimulation (tDCS) over a specific region of the PFC would enhance both regulation processes. Thirty-three men with internet gaming disorder received active (1.5 mA for 20 minutes) and sham tDCS over the right dorsolateral PFC (dlPFC) one week apart in a randomized order. During each stimulation session, participants regulated craving for gaming during a regulation of craving (ROC) task and negative emotions during an emotion regulation (ER) task using cognitive reappraisal. Subjective ratings of craving and negative emotions and skin conductance responses (SCRs) were recorded. For both craving and negative emotions, tDCS of the right dlPFC facilitated downregulation and upregulation: active relative to sham tDCS decreased ratings (ROC: 95% CI of difference -1.38 to -0.56, p < 0.001; ER: -1.65 to -0.70, p < 0.001) and/or SCRs (ROC: -1.99 to -0.41 µs, p = 0.004) for downregulation, and increased ratings (ROC: 0.24 to 0.82, p = 0.001; ER: 0.26 to 0.72, p < 0.001) for upregulation. These findings provide the first experimental evidence confirming that tDCS of the right dlPFC enhances both craving- and negative-emotion-regulation. This suggests a promising approach for concurrently enhancing executive control over two central motivational drives underlying addictions.

Correlation between systemic osteoporosis and local bone erosion with rheumatoid arthritis patients in Chinese population.

OBJECTIVE: RA is a systemic auto-immune inflammatory disease that can lead to local bone erosions and generalized osteoporosis (OP). The aim of this study was to investigate the relationship between systemic osteoporosis and local bone erosion with RA patients in the Chinese population. METHODS: In total, 1235 patients with RA and 158 normal subjects were enrolled in this study. Clinical and laboratory features were recorded in detail. Information about functional class and physical activity was collected using specific questionnaires. Dual-energy X-ray absorptiometry was used to measure BMD. The MECALL castor-50-hf model X-ray scanner was used for two-hand (including wrist) photographs. RESULTS: The median Sharp scores differed significantly between the normal bone mass group, osteopenia group and OP group (P < 0.001). There was a modest negative linear correlation between Sharp and HAQ scores and longer disease duration (P < 0.001). There was a clear increasing trend in Sharp score, incidence of OP and HAQ score in the different DAS in 28 joints (DAS28) activity groups (P < 0.001). Spearman's correlation test showed that Sharp and HAQ scores were negatively correlated with BMD at all measured sites (femoral neck, total hip and L1-4) (P < 0.001). Logistic regression indicated that age, female gender, and Sharp and HAQ scores were independent risk factors in the occurrence of OP in RA patients. The use of DMARDs and BMI were protective factors for OP. CONCLUSION: These results suggest that BMD is associated with local bone erosion among Chinese patients with RA. Local bone erosion is closely related to clinical symptoms and BMD in patients with RA.

Endemic Variation of H9N2 Avian Influenza Virus in China.

Forty-two H9N2 subtype AIV strains were isolated from vaccinated commercial chickens in China from 2012 to 2015. Their HA genes had nucleotide sequence homology from 86.7% to 99.7%, and similarity to the classic vaccine strain was 88.6%-92.6%. A comparison was carried out with published HA genes (410 H9 strains) and whole genomes (306 strains) isolated in China during 2012-2015. Interestingly, 99.1% (448/452) of Chinese H9N2 AIV belonged to lineage h9.4.2, and 98.5% (445/452) of the viruses belonged to h9.4.2.5. Meanwhile, 99.6% (443/445) of lineage 9.4.2.5 viruses had PSRSSR↓GLF instead of PARSSR↓GLF motifs in the HA cleavage sites; 98.2% (444/452) of HA genes showed human receptor binding associated mutation Q226L. A total of 96.8% (337/348) of the viruses had three amino-acid deletions at 63-65 in the NA stalk, associated with enhanced virulence in chickens and mice; 97.1% (338/348) of M2 proteins had the S31N mutation associated with adamantane resistance in humans. Two H9 viruses isolated in this study were highly homologous to the human-origin H9N2 virus reported in 2013. The isolates were divided into four different genotypes (U, S, V, and W). Genotype S was the major one, accounting for 94.8% (330/348). Genotypes V and W were new reassortment genotypes, with genotype W recombined with the PB2 gene originating from the new wild waterfowl-like lineage. According to the cross-HI antibody titer data, HA gene evolution, and isolation history, the isolates were divided into A, B, and C antigenic groups successively. All the antigenic group viruses were found to circulate throughout China. This study emphasizes the importance of updated vaccine and strengthened veterinary biosecurity on poultry farms and trade markets.

Autoimmunity and dysmetabolism of human acquired immunodeficiency syndrome.

Acquired immunodeficiency syndrome (AIDS) remains ill-defined by lists of symptoms, infections, tumors, and disorders in metabolism and immunity. Low CD4 cell count, severe loss of body weight, pneumocystis pneumonia, and Kaposi's sarcoma are the major disease indicators. Lines of evidence indicate that patients living with AIDS have both immunodeficiency and autoimmunity. Immunodeficiency is attributed to deficits in the skin- and mucosa-defined innate immunity, CD4 T cells and regulatory T cells, presumably relating human immunodeficiency virus (HIV) infection. The autoimmunity in AIDS is evident by: (1) overproduction of autoantibodies, (2) impaired response of CD4 cells and CD8 cells, (3) failure of clinical trials of HIV vaccines, and (4) therapeutic benefits of immunosuppression following solid organ transplantation and bone marrow transplantation in patients at risk of AIDS. Autoantibodies are generated in response to antigens such as debris and molecules de novo released from dead cells, infectious agents, and catabolic events. Disturbances in metabolic homeostasis occur at the interface of immunodeficiency and autoimmunity in the development of AIDS. Optimal treatments favor therapeutics targeting on the regulation of metabolism to restore immune homeostasis.

Consistent Efficacy of Wendan Decoction for the Treatment of Digestive Reflux Disorders.

Gastroesophageal reflux disease (GERD) and bile reflux gastritis (BRG) are common gastrointestinal (GI) disorders with unmet medical needs. Traditional Chinese medicine has long been used for the treatment of GERD and BRG whereas the ginger-containing formula Wendan decoction (WDD) targets homeostatic disturbances characterized by "reflux" and "gut-juice exposure" problems. Here we used WDD as a therapeutic tool to unravel the common pathogenesis of GI reflux disorders. Control clinical trials reporting the WDD-treated patients with GERD and BRG were included in this systematic review and meta-analysis. Outcome measurements were clinical efficacy defined by symptom relief with normal GI endoscopy, radiology, and pathology. Eventually, 33 studies involved 3253 participants (1351 vs. 1035 of the BRG in 20 publications, 449 vs. 418 of the GERD in 13 studies, and 194 vs. 159 of relapse rate in 6 trials). Pooled data showed a consistent therapeutic efficacy of WDD on BRG (OR = 6.00, 95%C = 4.68-7.69) and GERD (OR = 4.39, 95%CI = 2.72-7.07). The relapse rate was 12.4% for WDD, significantly lower than 44.0% for conventional therapies (OR = 0.14, 95%CI = 0.08-0.26). The consistent therapeutic efficacy of the single TCM formula on GERD and BRD indirectly indicates reflux as a common pathogenesis in reflux-associated GI disorders.

Efficacy of the wen dan decoction, a Chinese herbal formula, for metabolic syndrome.

CONTEXT: Metabolic syndrome (MS) refers to the clustering of metabolic derangements that include hyperglycemia, dyslipidemia, hypertension, and chronic kidney impairment. Those conditions are well known as being synergistically responsible for morbidity from cardiovascular disease as well as for driving the global epidemic of type 2 diabetes. It is still unknown whether an exact unifying pathogenesis of MS exists. OBJECTIVE: The meta-analysis intended to analyze the use of Chinese medicine (CM) as a therapeutic tool to explore indirectly the unifying pathogenesis of MS. METHODS: PubMed, the Chinese National Knowledge Infrastructure (CNKI), and the Wanfang databases were systematically searched from inception to November 2013 for randomized, controlled trials (RCTs) that compared treatment efficacy for MS patients using the Wen Dan decoction (WDD), a CM formula, versus Western conventional therapeutics. OUTCOME MEASURES: Measurements included tests of the overall therapeutic efficacy of WDD for hyperglycemia, hypertension, dyslipidemia, and renal functions, and the study also analyzed adverse events. Data were expressed as weighted mean differences (WMDs), with 95% confidence intervals (95% CIs) and the odds ratio (OR). RESULTS: A total of 31 RCTs were included for meta-analysis, involving 2512 patients and including 1282 participants in the intervention groups. The pooled data favored WDD over the control treatments as follows: (1) hyperglycemia, with a WMD of -0.95 mmol/L (95% CI: -1.19 to -0.71); (2) hypertension, with a WMD of -7.40 mm Hg (95% CI: -9.86 to -4.93); (3) dyslipidemia: (a) total cholesterol (TC), with a WMD of -0.62 mmol/L (95% CI: -0.90 to -0.33); (b) triglycerides (TGs), with a WMD of -0.32 mmol/L (95% CI: -0.52 to -0.13); (c) low-density lipoproteins (LDPs), with a WMD of -0.22 mmol/L (95% CI: -0.41 to -0.02); and (d) high-density lipoproteins (HDPs), with a WMD of 0.10 mmol/L (95% CI: 0.03 to 0.17); and (4) of renal functions: (a) urea, with a WMD of -3.41 mmol/L (95% CI: -5.50 to -1.32) and (b) creatinine, with a WMD of -68.81 µmol/L (95% CI: -132.63 to -4.98). No statistical significance was documented in creatinine clearance between the 2 treatments with a WMD of 15.47 mL/min (95% CI: -7.71 to 38.64). The overall efficacy rate was 91.4% for WDD and 66.9% for the control treatments (OR: 5.33; 95% CI: 4.06 to 6.99). Adverse events were rare and minor. CONCLUSIONS: The consistent improvements found in metabolic profiles by use of the single herbal formula may indirectly imply a common pathogenesis in MS.

Wen Dan Decoction for hemorrhagic stroke and ischemic stroke.

OBJECTIVE: The use of traditional Chinese medicine (TCM) in stroke is increasing worldwide. Here we report the existing clinical evidence of the Pinellia Ternata containing formula Wen Dan Decoction (WDD) for the treatment of ischemic stroke and hemorrhagic stroke. METHODS: PubMed, CNKI, Wan Fang database, Cochrane Library and online Clinical Trial Registry were searched up to 26 February 2013 for randomized, controlled clinical trials (RCTs) using WDD as intervention versus Western conventional medicine as control to treat stroke. Clinical outcomes were improvement of the Neurological Functional Deficit Scores (NFDS) and overall therapeutic efficacy rates including rate of cure. Meta-regression analysis using Hedges'g was performed for RCTs with significant heterogeneity. RESULTS: A total of 22 RCTs of ischemic stroke and 4 RCTs of hemorrhagic stroke, involving 2214 patients (1167 used WDD), met our inclusion criteria. Meta-analysis of the 13 RCTs reporting NFDS improvement favored WDD over the control (mean difference=-3.40, 95% confidence intervals [CI]=[-4.64, -2.15]). Rate of overall therapeutic efficacy (odds ratio [OR]=3.39, 95%CI=[1.81, 6.37]) for hemorrhagic stroke were significantly higher in WDD treated patients than the control subjects. In the 1898 patients with ischemic stroke, WDD medication also achieved higher rates of cure (OR=2.22, 95%CI=[1.66, 2.97]) and overall therapeutic efficacy (OR=3.31, 95%CI=[2.54, 4.31]) than the conventional treatment. CONCLUSIONS: WDD displays benefits on improvement of neurological function and overall therapeutic efficacy in post-stroke patients. TCM such as WDD may serve as a therapeutic tool of dual actions to explore the common mechanisms underlying cerebral hemorrhage and ischemia.

Genetic variation and phylogenetic analysis of hemagglutinin genes of H9 avian influenza viruses isolated in China during 2010-2012.

Genetic variation and phylogenetic relationships of H9 avian influenza viruses (AIVs) were analyzed based on hemagglutinin (HA) gene sequences of 84 Chinese H9 reference viruses recently available in GenBank, 3 widely used vaccine strains and 29 novel isolates. The novel isolates were obtained from vaccinated poultry flocks in 11 provinces of China during 2010 to 2012. The nucleotide homologies of HA genes of these isolates ranged from 87.8-99.8%, and from 89.8-93.2% as compared with the vaccine strains. Among the 29 novel isolates and the 84 reference viruses, 69.9% of the them belonged to the lineage h9.4.2.5 and had the dominant PSRSSR↓GLF motifs in the HA cleavage sites, while 27.4% of the them belonged to the newly emerging lineage h9.4.2.6 and had the dominant PARSSR↓GLF motifs, no consecutive basic amino acids insertion, showing the characteristic feature of low-pathogenic AIV. All the lineage h9.4.2.5 viruses and 75% of the lineage h9.4.2.6 viruses had the substitution Q226L (in H3 numbering). Additional potential glycosylation site at residues 313-315 (NCS) were found merely in all the lineage h9.4.2.5 viruses. Our results demonstrated that lineage h9.4.2.5 was more dominant than other lineages as it harbored more viruses that widely distributed in China in recent years. New lineage h9.4.2.6 previously existed mainly in South China had emerged in North China. Updated vaccine and increased veterinary biosecurity on poultry farms and trade markets are needed to prevent and control avian influenza.

Treatment of pediatric refractory Crohn's disease with thalidomide.

AIM: To assess the efficacy and tolerability of thalidomide in pediatric Crohn's disease (CD). METHODS: Six patients with refractory CD received thalidomide at an initial dose of 2 mg/kg per day for one month, then increased to 3 mg/kg per day or decreased to 1 mg/kg per day, and again further reduced to 0.5 mg/kg per day, according to the individual patient's response to the drug. RESULTS: Remission was achieved within three months. Dramatic clinical improvement was demonstrated after thalidomide treatment. Endoscopic and pathological improvements were also observed after thalidomide treatment, which was well tolerated by all patients. CONCLUSION: Thalidomide is a useful drug for pediatric refractory CD.

[Efficiency of lactose-free formula feeding as an adjunctive therapy in infants with acute diarrhea].

OBJECTIVE: To study the efficiency of lactose-free formula feeding as an adjunctive therapy in infants with acute diarrhea. METHODS: A rigorous double-blind, randomized, controlled equivalence trial was performed. One hundred and twenty infants with acute diarrhea were randomly divided into two groups: lactose-free formula and conventional formula feeding. The two groups were given conventional medical treatment and oral rehydration therapy. The therapeutic effects were observed 1 week after treatment. RESULTS: The cure rate and the total effective rate were 58.3% and 96.7% respectively in the lactose-free formula group, and they were 8.3% and 85.0% respectively in the conventional formula group. There were significant differences in the therapeutic effect between the two groups (p<0.05). The duration of diarrhea remission (3.17+/-1.04 days) in the lactose-free formula group was significantly shorter than that in the conventional formula group (5.25+/-1.58 days) (p<0.05). After treatment the incidence of fecal flora disturbance was lower in the lactose-free formula group than that in the conventional formula group (p<0.05). No aderverse events were observed in the two groups. CONCLUSIONS: Lactose-free formula feeding together with conventional therapy can significantly shorten the disease course and improve the treatment outcome in infants with acute diarrhea.

[Long-term outcome of interventional therapy for malignant biliary obstruction: a retrospective analysis of 109 cases].

OBJECTIVE: To evaluate the long-term outcome and its relative influenced factors of interventional therapy in dealing malignant biliary obstruction (MBO). METHOD: 109 MBO patients, 54 males and 55 females, aged (71 +/- 12), underwent interventional therapy: 55 patients received percutaneous transhepatic cholangiography and drainage (PTCD), and 54 underwent bile duct stent implantation. One week later, total bilirubin (TB), direct bilirubin (DB), and alanine transaminase (ALT) were examined, and Child-Pugh scoring was conducted.38 of the patient underwent transcatheter arterial chemo-embolization (TACE). RESULTS: One week after drainage the levels of ALT, TB, and DB of the patients undergoing PTCD and stent implantation all decreased in comparison with those before the treatment, the levels of the stent implantation group being significantly lower than those of the PTCD group (P = 0.019, 0.002, and 0.002 respectively), but there was no significant difference in Child-Pugh scale between these 2 group (P = 0.396). One week after TACE the levels of TB, DB, and Child-Pugh scale of the TACE group were all significantly lower than those of the patients without TACE (P = 0.000, 0.002, and 0.002 respectively), however, there was no significant difference in ALT level between these 2 groups (P = 0.834). The cumulative mean survival time was 26.45 weeks [standard error (SE) 4.07], and the mean survival time of the PTCD group was 28.19 weeks (SE, 6.54), not significantly different from that of the stenting groups were [21.38 weeks (SE, 2.51), P = 0.713]. The mean survival time of the TACE group was 43.71 weeks (SE, 8.32), significantly longer than that of the patients without TACE [14.38 weeks (SE, 2.66), P = 0.000]. CONCLUSION: Stenting is more effective than PTCD on relieving jaundice when the decreasing extent of bilirubin level is concerned. TACE therapy following PTCD and stent implantation will significantly contribute to the survival time of MBO patients.

Characterization and expression of an actin-depolymerizing factor from Eimeria tenella.

Actin-depolymerizing factor (ADF) plays an important role in remodeling the actin cytoskeleton which contributes much to the invasion of host cells by the apicomplexan parasite. The gene encoding for Eimeria tenella ADF with one intron was cloned and identified by the E. tenella genome raw sequence data ( http://www.sanger.ac.uk/projects/E.tenella/ ). The deduced polypeptide sequence was only composed of 118 amino acids (13.14 kDa) without signal peptide and nuclear localization sequence. The amino acid sequence was most similar to the ADF of Toxoplasma gondii, 69.1%. Compared the putative three-dimensional structures between E. tenella and yeast, the actin filament binding sites on the segment from the alpha4-helices to the C-terminal were mostly missed in E. tenella. Real-time RT-PCR and dot blot both revealed that ADF expression was relatively stronger in the sporozoites and merozoites than in sporulated and unsporulated oocysts in both mRNA and protein levels. Northern blot analysis suggested that there was only one form of ADF transcripts in all different life stages of E. tenella. Actin-binding experiment showed that the recombinant fusion ADF protein could bind with actin, which indicated that ADF probably plays an important role in the invasion host of E. tenella.