自杀意念量表信效度评价及其在大学生中的应用

目的了解浙南山区大学生自杀意念的发生情况,为山区高校大学生的心理危机干预提供依据。方法采用分层整群抽样方法,对丽水市1所普通高校的2 346名浙南山区本科生进行自杀意念自评量表(SIOSS)调查,并对该量表进行信度和效度检验。结果浙南山区大学生中最近1 a内有自杀意念者占10.10%;自杀意念自评量表的结构模型较理想,共抽取绝望、乐观、自杀、睡眠及掩饰5个因子;除掩饰因子外,其余各因子及条目均与SDS、SCL-90聚合度良好;量表的Cronbach’sα系数为0.85,Spearman-Brown分半信度为0.83,重测信度为0.86;SIOSS筛检的敏感性、特异性及Kappa系数分别为100%,97.09%及0.95。结论浙南山区大学生自杀意念发生率处于较高水平,自杀意念与心理健康不良有统计学关联。     

A Phase I Trial of IGF-1R Inhibitor Cixutumumab and mTOR Inhibitor Temsirolimus in Metastatic Castration-resistant Prostate Cancer

BackgroundDespite frequent PTEN (phosphatase and tensin homologue) loss and Akt/mammalian target of rapamycin (mTOR) signaling in prostate cancer, the disease is insensitive to single-agent mTOR inhibition. Insulin-like growth factor-1 receptor inhibition might mitigate the feedback inhibition by Torc1 inhibitors, suppressing downstream Akt activation and, thus, potentiating the antitumor activity of mTOR inhibition.Patients and MethodsIn the present phase I study, patients with metastatic castration-resistant prostate cancer received 6 mg/kg cixutumumab and 25 mg temsirolimus intravenously each week. The primary objective was safety and tolerability. Temsirolimus was decreased if ≥ 2 dose-limiting toxicities (DLTs) were observed in 6 patients. The correlative analyses included measurement of circulating tumor cells, [18F]-fluoro-2-deoxyglucose positron emission tomography, 16β-[18F]-fluoro-α-dihydrotestosterone positron emission tomography, and tumor biopsy.ResultsA total of 16 patients were enrolled across 3 cohorts (1, −1, −2). Two DLTs (grade 3 oral mucositis) were observed in cohort 1 (temsirolimus, 25 mg), and 1 DLT (grade 3 lipase) in cohort −1 (temsirolimus, 20 mg). The most common adverse events included hyperglycemia (100%; 31% grade 3), oral mucositis (63%; 19% grade 3), and diarrhea (44%; 0 grade 3). Low-grade pneumonitis occurred in 7 of 11 patients (44%; 0 grade 3), prompting the opening of a 3-weekly cohort (temsirolimus, 20 mg/kg), without pneumonitis events. No patient had a >50% decline in prostate-specific antigen from baseline. The best radiographic response was stable disease, with median study duration of 22 weeks (range, 7-63 weeks).ConclusionsDespite a strong scientific rationale for the combination, temsirolimus plus cixutumumab demonstrated limited antitumor activity and a greater than expected incidence of toxicity, including low-grade pneumonitis and hyperglycemia. Hence, the trial was stopped in favor of alternative androgen receptor/phosphatidylinositol 3-kinase–directed combinatorial therapies.     

经皮后外侧螺钉内固定治疗距骨颈骨折21例疗效分析

目的回顾性分析经皮后外侧入路螺钉内固定手术方式治疗距骨颈骨折的临床疗效。方法 2008年6月～2010年10月对收治的21例距骨颈骨折患者,在X线透视下采用经皮后外侧入路螺钉内固定手术治疗,全部病例获得10～24个月随访(平均18个月)。观察手术时间、手术切口长度、术中出血量、住院时间、术后伤口愈合、骨折愈合及内固定情况,同时按Olerud和Molander踝关节骨折术后评分系统对踝关节功能进行评估。结果手术时间48～80min(平均64min),手术切口长度0.5～1.5cm(平均1cm),术中出血量5～20ml(平均10ml),住院时间3～7天(平均4.5天),所有病例伤口均无裂开、坏死、感染,未见足部感觉麻木和运动功能障碍。术后4～6个月X线片示骨折均愈合,平均4.7个月,无内固定松动,断裂。按Olerud和Molan-der踝关节骨折术后功能评分平均为87.5分,优良率为83.3%。结论距骨颈骨折经皮后外侧入路螺钉内固定是一个微创的手术方法,具有对距骨血供影响小,骨折愈合率高,并发症少,术后恢复快,患者功能恢复良好等优点。     

Transient receptor potential melastatin 2 contributes to neuroinflammation and negatively regulates cognitive outcomes in a pilocarpine-induced mouse model of epilepsy

Neuroinflammation contributes to the generation of epileptic seizures and is associate with neuropathology and comorbidities. Transient receptor potential melastatin 2 (TRPM2) expresses in various cell types in the brain. It plays a pathological role in a wide range of neuroinflammatory diseases, but has yet been studied in epilepsy. Here, a temporal lobe epilepsy model was generated by pilocarpine administration in mice. At 24 h, knockout (KO) TRPM2 alleviated the level of neuroinflammation, showing a reduction of IL-1β, TNF-α, CXCL2 and IL-6 mRNA production, NLRP3, ASC, and Caspase-1 protein expression and glial activation. Moreover, KO TRPM2 alleviated neurodegeneration, concurrent with reduced Beclin-1 and ATG5 protein expression. Later, KO TRPM2 ameliorated the epilepsy-induced psychological disorders, with improved performance in the open-field, Y maze and novel object recognition test. Together, these results suggest that TRPM2 facilitates epilepsy-related brain injury and may shed light on its potential as a therapeutic target for epilepsy-associated neuropathology and comorbidities.     

miR-455-5p suppresses hepatocellular carcinoma cell growth and invasion via IGF-1R/AKT/GLUT1 pathway by targeting IGF-1R

Hepatocellular carcinoma (HCC) is among the most frequently observed forms of cancer. MicroRNAs (miRNAs) are increasingly thought to play a key role in regulating the onset and progression of a wide range of cancer types. In the present report, we found that miR-455-5p expression was significantly decreased in both HCC patient tumor tissues and cell lines, and that this reduction in expression was linked to poorer patient outcomes. When we overexpressed miR-455-5p in HCC cell lines (Huh7 and HepG2), this was linked with impaired proliferation, colony formation, migration, and invasion. We further found that this miRNA was able to directly bind the insulin growth factor receptor (IGF-1R) 3′-untranslated region, thereby suppressing IGF-1R expression in HCC cells. Consistent with this, miR-455-5p overexpression was associated with reduced glucose transporter (GLUT) 1 expression, which in turn inhibited HCC cell uptake of glucose, production of lactate, and generation of ATP. Together these results thus indicate that mIR-455-5p is able to suppress tumor functionality via impairing glycolysis in HCC cells, highlighting this miRNA as a potential target for anti-cancer therapeutic interventions.     

The protective effect of myricitrin in osteoarthritis: An in vitro and in vivo study

Osteoarthritis (OA) is a long-term, chronic, progressive joint condition caused by a pathology characterized by the deterioration of joint cartilage and proliferation of subchondral bone. Myricitrin (Myr) is a flavonoid compound extracted from myrica rubra with potent anti-inflammatory properties, as demonstrated in various studies. However, the mechanisms by which Myr plays a protective role in OA are not completely understood. In this study, the anti-inflammatory properties and potential mechanisms of Myr on mouse chondrocytes treated with interleukin (IL) −1beta (β) were explored in vitro and the role of Myr in a mouse model of OA in vivo. The production of pro-inflammatory factors, such as IL-6, tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2) and nitric oxide (NO) were assessed by enzyme linked immunosorbent assay (ELISA) and the Griess reaction. Protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), Collagen-II, matrix metalloproteinase(MMP)-13, MMP-3, thrombospondin motifs 5(ADAMTS5), inhibitor of nuclear factor kappa-B (IκB), p-IκB, p65, p-p65, c-jun-terminal kinase (JNK), p-JNK, extracellular regulated protein kinases (ERK), p-ERK, p38 and p-p38 were quantified using Western blot analysis. In the present study, we found that Myr inhibited IL-1β-induced production of NO and PGE2, expression of MMP-13, MMP-3 and ADAMTS5 and degradation of collagen-II in mouse chondrocytes. Mechanistically, Myr inhibited the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) treated with IL-1β in mouse chondrocytes. In vivo, Myr decreased OA Research Society International (OARSI) scores in a surgically-induced mouse model of OA. These data suggest that Myr could be developed as a potential therapy for OA.     

Short term exposure to di-n-butyl phthalate (DBP) disrupts ovarian function in young CD-1 mice

Di-n-butyl phthalate (DBP) is present in many beauty and medical products. Human exposure estimates range from 0.007–0.01 mg/kg/day in the general population and up to 0.233 mg/kg/day in patients taking DBP-coated medications. Levels of phthalates tend to be higher in women, thus, evaluating ovarian effects of DBP exposure is of great importance. Mice were given corn oil (vehicle) or DBP at 0.01, 0.1, and 1000 mg/kg/day (high dose) for 10 days to test whether DBP causes ovarian toxicity. Estrous cyclicity, steroidogenesis, ovarian morphology, and apoptosis and steroidogenesis gene expression were evaluated. DBP exposure decreased serum E₂ at all doses, while 0.1DBP increased FSH, decreased antral follicle numbers, and increased mRNA encoding pro-apoptotic genes (Bax, Bad, Bid). Interestingly, mRNAs encoding the steroidogenic enzymes Hsd17b1, Cyp17a1 and Cyp19a1 were increased in all DBP-treated groups. These novel findings show that DBP can disrupt ovarian function in mice at doses relevant to humans.     

畲医诊疗方法与病名概述

探讨畲医的诊疗方法,疾病的命名与分类。通过深入浙江、福建等畲族村镇,走访近百名畲医后整理而成。     

Ghrelin protects against palmitic acid or lipopolysaccharide-induced hepatocyte apoptosis through inhibition of MAPKs/iNOS and restoration of Akt/eNOS pathways

BacgroundGhrelin has been shown to exert various biological functions. However, the effect and mechanism of ghrelin on PA- or LPS-induced liver injury remains unknown.MethodsNormal human hepatocyte lines (LO2 and 7701) were pretreated with ghrelin (10⁻⁸ M) for 30 min before stimulation with lipopolysaccharide (LPS) or palmitic acid (PA). The proliferation and apoptosis of cells were detected with CCK8, Hoechst staining and flow cytometric analysis. Levels of NO of cell supernatants were examined by enzyme-linked immunosorbent assay (ELISA). The protein levels and mRNA of target genes of endothelial NOS (eNOS) and inducible NOS (iNOS) were measured by western blotting, immunofluorescence and quantitative real-time polymerase chain reaction (qRT-PCR). The expression of Bax, Bcl2, caspase 3, p-Akt, p-P38 and p-JNK were detected by western blotting.ResultsResults of CCK8, Hoechst staining and flow cytometric analysis showed that ghrelin-pretreatment attenuated LPS- or PA- induced cellular proliferation inhibition and apoptosis induction. ELISA results revealed that ghrelin pretreatment reduced levels of NO of cell supernatants (P < 0.05). Results of western blotting and immunofluorescence showed that protein levels of iNOS in ghrelin- pretreated group were significantly reduced compared with LPS- or PA- treated group, while protein levels of eNOS were restored by ghrelin pretreatment. Results of qRT-PCR showed that mRNA levels of Bax, iNOS were reduced by ghrelin pretreatment, while levels of mRNA of Bcl2 and eNOS were increased (P < 0.05). The protein levels of pAkt were significantly increased by ghrelin pretreatment, while the protein levels of p-JNK, p-P38 and caspase 3 were reduced. The restoration of eNOS could be reversed by an Akt inhibitor.ConclusionsGhrelin pretreatment attenuated LPS- or PA-induced hepatocyte apoptosis, which may least partly via inhibition of mitogen-activated protein kinases (MAPKs)/iNOS and restoration of Akt/eNOS pathways.