Down-regulation of miR-3068-3p enhances kcnip4-regulated A-type potassium current to protect against glutamate-induced excitotoxicity.

The main cause of excitotoxic neuronal death in ischemic stroke is the massive release of glutamate. Recently, microRNAs (miRNAs) have been found to play an essential role in stroke pathology, although the molecular mechanisms remain to be investigated. Here, to identify potential candidate miRNAs involved in excitotoxicity, we treated rat primary cortical neurons with glutamate and found that miR-3068-3p, a novel miRNA, was up-regulated. We hypothesized that restoring miR-3068-3p expression might influence the neuronal injury outcomes. The inhibition of miR-3068-3p, using tough decoy lentiviruses, significantly attenuated the effects of glutamate on neuronal viability and intracellular calcium overload. To unravel the mechanisms, we employed bioinformatics analysis and RNA sequencing to identify downstream target genes. Additional luciferase assays and western blots validated kcnip4, a Kv4-mediated A-type potassium current (IA ) regulator, as a direct target of miR-3068-3p. The inhibition of miR-3068-3p increased kcnip4 expression and vice versa. In addition, the knockdown of kcnip4 by shRNA abolished the protective effect of miR-3068-3p, and over-expressing kcnip4 alone was sufficient to play a neuroprotective role in excitotoxicity. Moreover the inhibition of miR-3068-3p enhanced the IA density, and the pharmacological inhibition of IA abrogated the protective role of miR-3068-3p inhibition and kcnip4 over-expression. Therefore, we conclude that inhibition of miR-3068-3p protects against excitotoxicity via its target gene, kcnip4, and kcnip4-regulated IA . Our data suggest that the miR-3068-3p/kcnip4 axis may serve as a novel target for the treatment of ischemic stroke.

The mediating effect of health anxiety in the relationship between functional somatic symptoms and illness behavior in Chinese inpatients with depression.

BACKGROUND: Functional somatic symptoms in depression disorder may cause inappropriate illness behavior hindering the treatment process. Health anxiety may play a role in this relationship, but few studies have examined it. The current study aimed to investigate the role of health anxiety in the relationship between functional somatic symptoms and illness behavior in patients with depression. METHODS: The present study recruited 323 hospitalized patients with depression to complete the Patient Health Questionnaire-15, Whiteley-Index-7, and Scale for the Assessment of Illness Behavior, then constructed a structural equation model to examine whether health anxiety mediated the relationship between functional somatic symptoms and illness behavior. RESULTS: The results showed significant correlations between any two of the three variables of interest. More importantly, health anxiety played a partially mediating role (42.86%) in the relationship between functional somatic symptoms and illness behavior. Further analysis suggested that elderly patients reached higher health anxiety than younger patients when their functional somatic symptoms were mild. CONCLUSIONS: These results highlight that health anxiety may mediate the influence of functional somatic symptoms on illness behavior. The implications of assessing and intervening in health anxiety in patients with depression were discussed.

The prevalence, metabolic disturbances and clinical correlates of recent suicide attempts in Chinese inpatients with major depressive disorder.

BACKGROUND: Metabolic disturbances have been correlated with suicidality, but little is known about the association between suicide risk and metabolic disturbances among individuals with depression. This study was to evaluate the prevalence and clinical correlations, especially cardio-metabolic associated factors of recent suicide attempts in Chinese patients with major depressive disorder (MDD). METHODS: A total of 288 MDD inpatients were recruited. Their clinical and demographic data together with plasma glucose, lipid and thyroid function parameters were collected. Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS) and Eysenck Personality Questionnaire (EPQ) were rated for most of the patients. RESULTS: Of these MDD inpatients, 20.14% had attempted suicide during the past 1 month. Compared to those who had not attempted suicide, the suicide attempters had a significantly longer duration of illness, lower low-density lipoprotein (LDL) cholesterol, lower total cholesterol, and more psychotic symptoms. However, all these significant results did not survive after the bonferroni correction (all p > 0.05). A logistic regression analysis indicated that suicide attempts were associated with the lower total cholesterol and more psychotic symptoms. CONCLUSIONS: Our findings support the hypothesis of the association of low plasma cholesterol level and recent suicidal attempts in patients with MDD.

Gremlin2 Suppression Increases the BMP-2-Induced Osteogenesis of Human Bone Marrow-Derived Mesenchymal Stem Cells Via the BMP-2/Smad/Runx2 Signaling Pathway.

Osteoblasts are essential for maintaining skeletal architecture and modulating bone microenvironment homeostasis. From numerous associated investigations, the BMP-2 pathway has been well-defined as a vital positive modulator of bone homeostasis. Gremlin2 (Grem2) is a bone morphogenetic protein (BMP) antagonists. However, the effect of Grem2 on the BMP-2-induced osteogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs) remains ambiguous. This study aimed to analyze the procedure in vitro and in vivo. The differentiation of hBMSCs was assessed by determining the expression levels of several osteoblastic genes, as well as the enzymatic activity and calcification of alkaline phosphatase. We found that Grem2 expression was upregulated by BMP-2 within the range of 0-1 µg/mL, and significant increases were evident at 48, 72, and 96 h after BMP-2 treatment. Si-Grem2 increased the BMP-2-induced osteogenic differentiation of hBMSCs, whereas overexpression of Grem2 had the opposite trend. The result was confirmed using a defective femur model. We also discovered that the BMP-2/Smad/Runx2 pathway played an important role in the process. This study showed that si-Grem2 increased the BMP-2-induced osteogenic differentiation of hBMSCs via the BMP-2/Smad/Runx2 pathway. J. Cell. Biochem. 118: 286-297, 2017. © 2016 Wiley Periodicals, Inc.

ALDH2 is associated to alcohol dependence and is the major genetic determinant of "daily maximum drinks" in a GWAS study of an isolated rural Chinese sample.

Alcohol dependence (AD) is a moderately heritable phenotype with a small number of known risk genes mapped via linkage or candidate gene studies. We considered 313 males from among 595 members of documented, extended pedigrees in which AD segregates collected in Northern Hunan Province, China. A joint analysis of both males and females could not be performed as the difference in alcohol consumption variance was too large. Genome-wide association analyses were performed for approximately 300,000 single nucleotide polymorphisms (SNPs). Significant associations found in the ALDH2 region for AD (minimum P = 4.73 × 10(-8)) and two AD-related phenotypes: flushing response (minimum P = 4.75 × 10(-26)) and maximum drinks in a 24-hr period (minimum P = 1.54 × 10(-16)). Association of previous candidate SNP, rs10774610 in CCDC63, was confirmed but resulted from linkage disequilibrium with ALDH2. ALDH2 is strongly associated with flushing response, AD, and maximum drinks in males, with nonsynonymous SNP rs671 explaining 29.2%, 7.9%, and 22.9% of phenotypic variation, respectively, in this sample. When rs671 was considered as a candidate SNP in females, it explained 23.6% of the variation in flushing response, but alcohol consumption rates were too low among females-despite familial enrichment for AD-for an adequate test of association for either AD or maximum drinks. These results support a mediating effect of aldehyde dehydrogenase deficiency on alcohol consumption in males and a secondary, culturally mediated limitation on alcohol consumption by females that should be appropriately modeled in future studies of alcohol consumption in populations where this may be a factor.

Alcohol and alcohol-related harm in China: policy changes needed.

In China, alcohol consumption is increasing faster than anywhere else in the world. A steady increase in alcohol production has also been observed in the country, together with a rise in alcohol-related harm. Despite these trends, China's policies on the sale and consumption of alcoholic beverages are weak compared with those of other countries in Asia. Weakest of all are its policies on taxation, drink driving laws, alcohol sale to minors and marketing licenses. The authors of this descriptive paper draw attention to the urgent need for public health professionals and government officials in China to prioritize population surveillance, research and interventions designed to reduce alcohol use disorders. They describe China's current alcohol policies and recent trends in alcohol-related harm and highlight the need for health officials to conduct a thorough policy review from a public health perspective, using as a model the World Health Organization's global strategy to reduce the harmful use of alcohol.

En Chine, la consommation d'alcool augmente plus rapidement que partout ailleurs dans le monde. Une augmentation constante de la production d'alcool a également observée dans le pays, ainsi qu'une augmentation des méfaits de l'alcool. Malgré ces tendances, les politiques de la Chine en matière de vente et de consommation de boissons alcoolisées sont faibles comparées à celles des autres pays d'Asie. Les plus faibles de toutes sont ses politiques sur la taxation, les lois relatives à l'alcool au volant, la vente d'alcool aux mineurs et la commercialisation des licences. Les auteurs de cet article descriptif attirent l'attention sur la nécessité urgente pour les professionnels de la santé publique et les fonctionnaires gouvernementaux chinois d'accorder la priorité à la surveillance de la population, la recherche et les interventions destinées à réduire les troubles liés à la consommation d'alcool. Ils décrivent les politiques actuelles sur l'alcool en Chine et les tendances récentes des méfaits de l'alcoolisme. Ils soulignent également la nécessité pour les autorités sanitaires de procéder à un examen approfondi de la politique dans une perspective de santé publique, en prenant comme modèle la stratégie globale de l'Organisation mondiale de la Santé afin de réduire l'usage nocif de l'alcool.

En China, el consumo de alcohol está aumentando con mayor rapidez que en cualquier otro lugar del mundo, y también se ha observado un crecimiento constante de la producción de alcohol en el país, junto con un aumento de los daños relacionados con esta sustancia. A pesar de estas tendencias, las políticas chinas sobre la venta y consumo de bebidas alcohólicas son débiles en comparación con las de otros países asiáticos. Las políticas más débiles son las que regulan los impuestos, las leyes de consumo y conducción, la venta de alcohol a menores de edad y las licencias para la venta de alcohol. Los autores de este artículo descriptivo llaman la atención sobre la necesidad urgente de que los funcionarios gubernamentales y los profesionales de la sanidad pública chinos den prioridad a la vigilancia de la población, a la investigación y a las intervenciones diseñadas para reducir los trastornos provocados por el consumo de alcohol. Describen las políticas actuales chinas relativas al alcohol, así como las tendencias presentes de los daños relacionados con el alcohol y destacan la necesidad de que los funcionarios de salud lleven a cabo una revisión de toda la política desde la perspectiva de la sanidad pública, usando como modelo la estrategia global de la Organización Mundial de la Salud para reducir el uso nocivo de alcohol.

Outcome of the modified Dunn procedure in severe slipped capital femoral epiphysis.

BACKGROUND: The modified Dunn procedure has rapidly gained popularity as a treatment for slipped capital femoral epiphysis (SCFE) during the past few years. However, there is limited information regarding its safety and efficacy in severe slips with this procedure. The purpose of this study is to present clinical results and incidence of complications associated with the modified Dunn osteotomy in a consecutive series of severe SCFE cohort. PATIENTS AND METHODS: We retrospectively assessed the outcomes of all twenty patients who had been treated with the modified Dunn procedure in our tertiary-care institution. According to the Loder and Fahey criteria, all cases were classified as severe slips; nineteen cases were stable, and one case was an unstable slip. All surgical procedures were performed by one senior orthopedic surgeon who had specific training in the modified Dunn procedure. Operative reports, outpatient records, follow-up radiographs, and the intraoperative findings were reviewed to determine the demographic information, type of fixation, final slip angle, presence of avascular necrosis (AVN), and any additional complications. The mean age of the patients was 13.2 ± 1.6 years (range, 10 to 17 years). Twenty patients (twenty-one hips) with a mean of 31.2 ± 14 months (range, 12 to 57 months) follow-up met the inclusion criteria. Pain and function were assessed by the modified Harris score and WOMAC score. Radiographic anatomy was measured using the slip angle and α-angle. The radiographic findings related to the anatomy of the femoral head-neck junction, as well as signs of early-onset of osteoarthritis (OA) and AVN, were evaluated pre- and postoperatively. RESULTS: Overall, nineteen patients had excellent clinical and radiographic outcomes with respect to hip function and radiographic parameters. One patient (5%) who developed implant failure at 3 months postoperatively had a poor outcome. The mean preoperative slip angle was corrected from 63.2 ± 8.1° (range, 51 to 84°) to a normal value of 7.5 ± 3.5° (range, 2 to 15°) (p < 0.01). The mean α-angle was improved from an average of 94.5 ± 21.1° (range, 61 to 123°) to postoperative 42 ± 6.4° (range, 25 to 55°) (p < 0.01). The mean modified Harris hip and WOMAC scores postoperatively were 96.7 ± 13.4 (range, 40 to 100) and 95.4 ± 10.6 (range, 38 to 100), respectively. There were no cases of the development of femoroacetabular impingement (FAI) and the progression of OA. We did not record any case of AVN, closure of the growth plate, heterotopic ossification (HO), trochanteric nonunion, or limb length discrepancy that occurred postoperatively either at the most recent follow-up. CONCLUSIONS: Our series of severe SCFEs treated with the modified Dunn osteotomy demonstrated that the procedure is safe and capable of restoring more normal proximal femoral anatomy by maximum correction of the slip angle, minimizing probability of secondary FAI and early onset of OA. However, despite its lower surgical complication rate compared with alternative treatment described in the literature for SCFE, AVN can and do occur postoperatively which should always be concerned in every hip.

5-HT2A receptor gene polymorphism and negative symptoms in first episode (drug-naive) Chinese Han nationality individuals with schizophrenia.

OBJECTIVE: To investigate whether the 5-hydroxytryptamine 2A receptor (5-HT2A) gene T102C polymorphism is associated with the severity symptoms and negative symptoms in the first episode Chinese Han nationality patients with schizophrenia. METHODS: Altogether 201 first episode Chinese Han nationality patients with schizophrenia were enrolled in this study. Genotyping of 5-HT2A gene T102C polymorphism was performed by PCR-RFLP technique. The positive and negative Symptom Scale (PANSS) was used for the evaluation of the severity of psychotic symptoms before any drug treatment. RESULTS: 5-HT2A receptor 102-T/T genotype was significantly associated with both the PANSS total and negative symptom subscale baseline scores before the treatment, but not with the positive and general psychopathology subscales. CONCLUSION: 5-HT2A T102C functional polymorphism may play a role in negative symptoms and prognosis of Chinese Han nationality people with schizophrenia.

The synergistic effect of dual use of amphetamine-type stimulants and ketamine on drug-induced psychotic symptoms in Chinese synthetic drug users.

The use of amphetamine-type stimulants (ATS) and ketamine is of particular clinical concern because of its associated psychotic symptoms. In Chinese clinical practice, ATS and ketamine are commonly used simultaneously, but very few studies have reported the symptom profile of users who use both drugs. This study determined whether the combined use of ATS and ketamine is associated with more psychotic symptoms than either ATS or ketamine alone. According to drug use characteristics, 375 Chinese synthetic drug users were categorized into 2 pairs of comparison groups: ATS-only (n=125) vs. ATS-mainly (ATS most of the time and ketamine sometimes, n=150) and ketamine-only (n=38) vs. ketamine-mainly (ketamine most of the time and ATS sometimes, n=62). We used the Chinese Brief Psychiatric Rating Scale (BPRS) to assess these patients' psychotic symptoms. ATS-mainly group had more anxiety/depression and anergia symptoms than ATS-only group (p<0.001), and ketamine-mainly group had more thinking-disorder, activity and hostility-suspicion symptoms than ketamine-only group (p≤0.001). These findings indicate that ATS may exacerbate the thinking-disorders, activity and hostility-suspicion symptoms of ketamine users, and ketamine may exacerbate anxiety/depression and anergia symptoms of ATS users.

Influence of video-assisted thoracoscopic lobectomy on immunological functions in non-small cell lung cancer patients.

In this study, we compared the effects of video-assisted thoracic surgery (VATS) and traditional open surgery (TOS) on immune system functioning in non-small cell lung cancer (NSCLC) patients. We enrolled 122 NSCLC patients in this study. The patients were randomly divided into VATS group (n = 61) and TOS group (n = 61). Plasma DNA concentration was analyzed by fluorescence quantitative PCR. Automatic blood analyzer was used to measure WBC-C, and immune nephelometry was employed to assess hs-CRP concentrations. The number of CD3+T, CD4+T and CD8+T lymphocytes in peripheral blood was estimated by flow cytometry. ELISA was used to quantify the levels of IGFBP-3, VEGF and IL-6. Compared to the TOS group, surgery-related blood loss and pain score on day 1 after surgery were lower in VATS group. After surgery, the out-of-bed activity occurred earlier and in-hospital stays were shorter in the VATS group compared to the TOS group. Plasma free DNA concentration of VATS group patients at first, third and fifth days after surgery was lower than that of the TOS group. WBC-C and hs-CRP levels were lower in the VATS group at each time point after surgery. The number of CD3+T, CD4+T, CD8+T lymphocytes and CD4+/CD8+ was lower in the TOS group compared to VATS group. Plasma IGFBP-3, VEGF and IL-6 levels were significantly lower in VATS group compared to the TOS group. Finally, incidence of complications in the VATS group was dramatically lower than the TOS group (all P < 0.05). Based on our findings, compared to TOS, VATS significantly decreased the incidence of acute-phase reaction and lowered the inhibition of immune functions after surgery.

Prevalence and correlates of HIV and HCV infection among amphetamine-type stimulant users in 6 provinces in China.

BACKGROUND: China has experienced an epidemic of amphetamine-type stimulant (ATS) use in recent years. The present study explored the status and correlates of HIV and hepatitis C virus (HCV) infection among ATS users in China. METHODS: A multicenter cross-sectional study of HIV and HCV status and associated behaviors among ATS users was conducted in 6 provinces from September 2009 to December 2010. Socioeconomic/behavioral risk factors were measured. Blood samples were collected to test for HIV and HCV antibodies. RESULTS: Of the 1327 ATS users, the prevalence of HIV and exposure to HCV were 4.5% and 43.5%, respectively, with large geographic variations (0%-20.3% and 8.6%-67.1%, respectively). HIV infection was independently associated with living in Yunnan province [adjusted odds ratio = 15.8; 95% confidence interval (CI): 2.0 to 125.1), polydrug use (adjusted odds ratio = 2.6; 95% CI: 1.3 to 5.4), increased frequency of sexual behavior (adjusted odds ratio = 2.0; 95% CI: 1.1 to 4.1), history of sex with sexually transmitted infection-positive persons (adjusted odds ratio = 11.4; 95% CI: 1.3 to 98.9), and HCV infection (adjusted odds ratio = 2.8; 95% CI: 1.2 to 6.7). HCV was associated with study site, marital status, unemployment (adjusted odds ratio = 1.8; 95% CI: 1.3 to 2.4), a longer duration of ATS use, and history of injection use of ATS (adjusted odds ratio = 13.3; 95% CI: 1.5 to 116.1). CONCLUSIONS: The prevalence of HIV was high among ATS users in Yunnan province but quite rare elsewhere, and the prevalence of exposure to HCV was high in 6 provinces. Risk factors emphasize the need for new prevention strategies toward this population at risk in China.