High DPP4 expression predicts poor prognosis in patients with low-grade glioma.

Dipeptidyl peptidase-IV (DPP4) plays a key role in tumor development; however, its role in glioma pathogenesis has not been determined. Here, we aimed to investigate the expression pattern of DPP4 and explore the association between expression and patient prognosis in glioma. DPP4 levels were investigated using qRT-PCR, immunohistochemistry and western blot in a rat model of glioma and also in patient samples. The relationship between DPP4 levels, WHO pathological grade gliomas, and isocitrate dehydrogenase 1 and 2 (IDH1/2) status was assessed in patient samples. Our data indicated that DPP4 levels were markedly increased in a rat model of glioma (p < 0.05, p < 0.01) and aslo in patient samples. Furthermore, the elevation of DPP4 levels in the samples obtained from pateints was associated with the pathogical grade of glioma and the IDH1/2 status (p < 0.01, p < 0.001). High DPP4 levels decreased the survival probability of patients with low-grade glioma (LGG). The data from patient samples showed that DPP4 expression increased with the pathological grade. Increased expression of DPP4 could be a promising index for determining the prognosis of glioma.

Associations of polymorphisms in TXNIP and gene-environment interactions with the risk of coronary artery disease in a Chinese Han population.

Single nucleotide polymorphisms (SNPs) in thioredoxin-interacting protein (TXNIP) gene may modulate TXNIP expression, then increase the risk of coronary artery disease (CAD). In a two-stage case-control study with a total of 1818 CAD patients and 1963 controls, we genotyped three SNPs in TXNIP and found that the variant genotypes of SNPs rs7212 [odds ratio (OR) = 1.26, P = 0.001] and rs7211 (OR = 1.23, P = 0.005) were significantly associated with increased CAD risk under a dominant model. In haplotype analyses, compared with the reference haplotype, haplotype 'G-T' had a 1.22-fold increased risk of CAD (P = 0.003). We also observed the cumulative effects of SNPs rs7212 and rs7211 on CAD risk and the severity of coronary atherosclerosis. Moreover, the gene-environment interactions among the variant genotypes of SNP rs7212, smoking habit, alcohol drinking habit and history of type 2 diabetes were associated with a 3.70-fold increased risk of CAD (P < 0.001). Subsequent genotype-phenotype correlation analyses further observed the significant effects of SNP rs7212 on TXNIP mRNA expression, plasma TXNIP and malondialdehyde levels. Taken together, our data suggest that TXNIP SNPs may individually and cumulatively affect CAD risk through a possible mechanism for regulating TXNIP expression and gene-environment interactions.

Associations of lipid levels susceptibility loci with coronary artery disease in Chinese population.

BACKGROUND: Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) that were associated with blood lipid levels in Caucasians. This study investigated whether these loci influenced lipid levels and whether they were associated with the risk of coronary artery disease (CAD) and its angiographic severity in Chinese population. METHODS: Six SNPs were genotyped in 1100 CAD cases and 1069 controls using the high-resolution melting (HRM) method. Coronary atherosclerosis severity was assessed by the vessel scores and the Gensini scoring system. RESULTS: Among the 6 SNPs and the genetic risks scores (GRS), the minor alleles of HNF1A rs1169288 (odd ratio (OR) = 1.18, 95% confidence interval (CI) 1.05-1.33, P = 0.006) and MADD-FOLH1 rs7395662 (OR = 1.20, 95% CI 1.07-1.36, P = 0.002) as well as the GRS (P = 1.06 × 10(-5)) were significantly associated with increased risk of CAD after false discovery rate (FDR) correction. The vessel (P = 0.013) and Gensini scores (ß = 0.113, P = 0.002) differed among CAD patients with different SNP rs1169288 C > T genotypes. The multiple linear regression analyses using an additive model revealed that the minor allele C of SNP rs1169288 (ß = 0.060, P = 0.001) and the GRS (ß = 0.033, P = 3.59 × 10(-4)) were significantly associated with increased total cholesterol (TC) levels, the minor allele A of SNP rs7395662 (ß = -0.024, P = 0.007) and the GRS (ß = -0.013, P = 0.004) were significantly associated with decreased high-density lipoprotein cholesterol (HDL-c) levels. CONCLUSIONS: The present study demonstrated that SNPs rs1169288, rs7395662 and the GRS were significantly associated with lipid levels and the risk of CAD in Chinese population. Furthermore, the allele C of SNP rs1169288 increased the odds of coronary atherosclerosis severity.

A Nanofiber Mat With Dual Bioactive Components and a Biomimetic Matrix Structure for Improving Osteogenesis Effect.

The challenge of effectively regenerating bone tissue through tissue engineering technology is that most tissue engineering scaffolds cannot imitate the three-dimensional structure and function of the natural extracellular matrix. Herein, we have prepared the poly(L-lactic acid)-based dual bioactive component reinforced nanofiber mats which were named as poly(L-lactic acid)/bovine serum albumin/nanohydroxyapatite (PLLA/BSA/nHAp) with dual bioactive components by combining homogeneous blending and electrospinning technology. The results showed that these nanofiber mats had sufficient mechanical properties and a porous structure suitable for cell growth and migration. Furthermore, the results of cell experiments in vitro showed that PLLA/BSA/nHAp composite nanofiber mat could preferably stimulate the proliferation of mouse osteoblastic cells (MC3T3 cells) compared with pure PLLA nanofiber mats. Based on these results, the scaffolds developed in this study are considered to have a great potential to be adhibited as bone repair materials.

Inhibition of EZH2 attenuates inhibitory synaptic transmission via the pro-inflammatory pathway in rats.

Enhancer of zeste homolog 2 (EZH2), a subunit of the polycomb repressive complex 2 (PRC2), is associated with seizure development and epileptogenesis, however, the underlying mechanism of the process remains to be elucidated. This study focused on exploring whether EZH2 regulated gamma-aminobutyric acid (GABA)-mediated neurotransmission during seizure generation. Hyperthermia-induced seizures were generated in Sprague-Dawley (SD) rats using a hot (43.5 °C) bath method, and seizure severity was evaluated according to the Racine scale. The effect of treatment with the EZH2 pharmacological inhibitor GSK 126 on the GABA and pro-inflammatory cytokine levels was tested using enzyme-linked immunosorbent assay (ELISA). Miniature inhibitory postsynaptic currents (mIPSCs) were recorded using whole-cell patch clamp. In this study, our results showed that intracerebroventricular (i.c.v) injection of the EZH2 pharmacological inhibitor GSK 126 (10 nM) increased seizure severity and shortened seizure latency in a rat model of FS, and these effects were accompanied by reduced GABA content. Furthermore, GSK 126 (1 µM) treatment decreased the mean amplitude and frequency of the mIPSCs in cultured hippocampal neurons subjected to hyperthermia. Importantly, the same results were also obtained in cultured neurons infected with lentivirus carrying EZH2 shRNA. In addition, a significant increase in the pro-inflammatory cytokine (IL-1ß and TNF-α) levels was observed in rats after GSK 126 treatment, and IL-1ß administration increased seizure severity, suggesting that the inflammatory response was involved in the regulation of seizure development by EZH2. This study helps clarify the role of EZH2 in FS and supports EZH2 administration as an effective target for the management of seizure generation.

Systematic Review and Meta-Analysis of the Utility of Circular RNAs as Biomarkers of Hepatocellular Carcinoma.

Emerging studies have reported circRNAs were dysregulated in HCC. However, the clinical value of these circRNAs remains to be clarified. Herein, we aimed to comprehensively explore their association with the diagnosis, prognosis, and clinicopathological characteristics of HCC. PubMed, EMBASE, Web of Science, and Cochrane Library databases were comprehensively searched for eligible studies up to October 30, 2018. The diagnostic effect was evaluated by the pooled sensitivity, specificity, and other indexes. The pooled hazard ratio (HR) for overall survival (OS) and recurrence free survival (RFS) was calculated to assess the prognostic value. Ten studies on diagnosis, 12 on prognosis, and 23 on clinicopathology were identified from the databases. A total of 11 upregulated and 11 downregulated circRNAs showed an association with clinicopathological features of HCC. For the diagnosis analyses, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of circRNAs for HCC were 0.74 (95%CI: 0.65-0.82) and 0.76 (95%CI: 0.70-0.81), 3.1 (95%CI: 2.5-3.8), 0.34 (95%CI: 0.25-0.47), and 9 (95%CI: 6-14), respectively. The area under SROC curve (AUC) was 0.81 (95% CI: 0.78-0.84), indicating moderate diagnostic accuracy. In stratified analyses, the diagnostic performance of circRNAs varied based on the source of control and specimen type. For the prognosis analyses, increased expression of upregulated circRNAs was associated with worse OS (HR: 3.67, 95%: 2.07-6.48), while high expression of downregulated circRNAs was associated with better OS (HR: 0.38, 95%: 0.30-0.48). In conclusion, this study reveals that circRNAs may serve as promising diagnostic and prognostic biomarkers for HCC. However, further investigations are still required to explore the clinical value of circRNAs.

[Acupuncture Intervention Improves Behavior Reactions and Learning-memory Ability in Post-traumatic Stress Disorder Rats].

OBJECTIVE: To observe the therapeutic effect of acupuncture in the treatment of post-traumatic stress disorder (PTSD)-induced abnormal behavior reactions and learning-memory ability in rats with traumatic injury. METHODS: Sixty male SD rats were randomly divided into control, model, model＋animal capturing (capturing), medication and acupuncture groups (n＝12 rats in each). The PTSD model was established by "electric shock plus incarceration" method. Acupuncture was applied to "Baihui" (GV 20), and unilateral "Neiguan" (PC 6), "Shenmen" (HT 7) and "Taichong" (LR 3) once daily for 12 days. The rats in the medication group were treated by gavage of Paroxetine Hydrochloride solution (0.42 mg/mL), once daily for 12 days. The open field test containing horizontal (crossing grid lines) and rearing tests was performed for examining the rats' locomotor activity and anxiety-like behavior; and location navigation (escape latency) and special probe tests (platform quadrant crossing times) of Morris water maze tasks were detected for assessing the rats' learning-memory ability. On day 12 of the experiments, the rats were submitted to 3 consecutive sessions of open field tests for observing the time of familiar objects (TF) and the time of novelty object (TN) of exploration in 5 min (an object-location and an object-recognition tasks), followed by calculating the discrimination index [DI＝(TN－TF)/(TN＋TF)x100%]. RESULTS: After modeling, compared with the control group, the numbers of crossed grids and rearing, and DI were significantly decreased (P<0.05), while the number of fecal pellets and escape latency were significantly increased in both the model and capturing groups (P<0.05). After the intervention, the number of both crossed grids and rearing, platform quadrant crossing times, and DI were considerably increased (P<0.05), and the rats' escape latency and fecal pellet number were obviously decreased in both medication and acupuncture groups relevant to the model and capturing groups (P<0.05). No significant differences were found between the acupuncture and medication groups in the above mentioned 5 indexes (P>0.05)．. CONCLUSION: Acupuncture can effectively reduce anxiety-like behavior and improve the impaired learning-memory ability in PTSD rats.

Associations of P16INK4a promoter hypermethylation with squamous intra-epithelial lesion, cervical cancer and their clinicopathological features: a meta-analysis.

To assess the associations of P16INK4a methylation status with low-grade squamous intra-epithelial lesion (LSIL), high-grade squamous intra-epithelial lesion (HSIL), cervical cancer (CC) and their clinicopathological features, a meta-analysis with 29 eligible studies was conducted. Pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were estimated to assess the strength of the associations. Heterogeneity, sensitivity of pooled results and publication bias were also evaluated. Overall, there was an increasing trend of P16INK4a hypermethylation rates among LSIL (21.4%), HSIL (30.9%) and CC (35.0%) specimens. P16INK4a hypermethylation was significantly associated with the increased risk of LSIL, HSIL and CC, with the pooled ORs of 3.26 (95% CI: 1.86-5.71), 5.80 (95% CI: 3.80-8.84) and 12.17 (95% CI: 5.86-25.27), respectively. A significant association was also found between P16INK4a hypermethylation and smoking habit (OR = 3.88, 95% CI: 2.13-7.08). Taken together, meta-analysis results support P16INK4a hypermethylation as an epigenetic marker for the progression of cervical carcinogenesis.

Polymorphism in ERCC1 confers susceptibility of coronary artery disease and severity of coronary artery atherosclerosis in a Chinese Han population.

Excision repair cross-complementing 1 (ERCC1) gene encodes ERCC1 protein, which is mainly responsible for the repair of DNA damage in different diseases including coronary artery atherosclerosis by acting as a rate-limiting element in nucleotide excision repair (NER). Using a three-stage case-control study with 3037 coronary artery disease (CAD) patients and 3002 controls, we investigated associations of three single nucleotide polymorphisms (SNPs) with CAD risk and severity of coronary artery atherosclerosis in Chinese Han population. In the discovery set, the variant allele T of rs11615 was significantly associated with higher CAD risk (adjusted OR = 1.27, P = 0.006) and severity of coronary artery atherosclerosis (adjusted OR = 1.54, P = 0.003). These associations were more remarkable in the merged set (adjusted OR = 1.23, P = 8 × 10-6 for CAD risk; adjusted OR = 1.36, P = 4.3 × 10-5 for severity of coronary artery atherosclerosis). And the expression level of ERCC1 was significantly higher in CAD cases than controls. Multiplicative interactions among SNP rs11615, alcohol drinking, history of T2DM, and history of hyperlipidemia could increase 5.06-fold risk of CAD (P = 1.59 × 10-9). No significant association of rs2298881 and rs3212986 with CAD risk was identified. Taken together, SNP rs11615 in ERCC1 gene might confer susceptibility to CAD and severity of coronary atherosclerosis in a Chinese Han population.

[Point application in literature of Dunhuang stone chamber and its application].

Acupuncture-moxibustion material found in Dunhuang stone chamber shows academic value on research of acupuncture-moxibustion in Tang Dynasty and before. In the paper we summarize its medical prescriptions and the existing acupoint application contents. It is considered that its acupoint application is widely clinically used in dermatological department, cosmetology department, ophthalmology and otorhinolaryngology departments, paediatrics department, gynaecology department, anorectal department, orthopedics and traumatology department. It achieves remarkable effects in dermatological department, orthopedics and traumatology department. Medical literature of Dunhuang is a treasure of TCM with distinctive feature and it deserves to be further explored so as to serve the clinic and promote the inheritance and development of Dunhuang medicine, such as finding out high effect prescription.

[Exploration of acupoints selection law for post-traumatic stress disorder treated with acupuncture and moxibustion].

To analyze the modern clinical literature on post-traumatic stress disorder(PTSD) treated with acupuncture and moxibustion so as to summarize the acupoints selection law. The related articles from 2005 to 2014 were collected and then the frequencies were statistically analyzed. Finally 16 papers were gathered,while the main acupoints among the 23 acupoints refer to Baihui(GV 20),Sishencong(EX-HN 1),Shenting(GV 24),Fengchi(GB 20),Shenmen(HT 7),Neiguan(PC 6),Taichong(LR 3) and Sanyinjiao(SP 6). It is concluded that the law means taking smoothing liver and governor vessel to regulate the spirit as priority,and assisted by nourishing kidney and supporting yang to peace the spirit,as well as strengthening spleen and helping qi to smooth meridians.

Relationships between MGMT promoter methylation and gastric cancer: a meta-analysis.

A DNA repair enzyme, O6-methylguanine-DNA methyltransferase (MGMT), plays an important role in the development of gastric cancers. However, the role of MGMT promoter methylation in the occurrence of gastric cancer and its relationships with clinicopathologic characteristics has not been fully clarified. Thus, we performed a meta-analysis to evaluate the associations between MGMT promoter methylation and gastric cancer. Electronic databases, including PubMed and Web of Science, were used to systematically search related clinical studies published in English until April 1, 2016. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to evaluate the associations between MGMT promoter methylation and gastric cancer risk or clinicopathologic characteristics. A total of 16 studies including 1,935 patients and 1,948 control persons were included in the analysis. Our study suggested that MGMT promoter methylation frequency was associated with gastric cancer (OR=3.46, 95% CI: 2.13-5.61, P<0.001). Moreover, the frequency of MGMT promoter methylation in the no lymph node metastasis group was lower than that in lymph node metastasis group, with marginal significance (OR=0.65, 95% CI: 0.42-1.01, P=0.05). Additionally, the methylation rate of the MGMT promoter was much lower in patients without distant metastases than in those with metastases (OR=0.27, 95% CI: 0.18-0.40, P<0.001). No significant association of MGMT promoter methylation with Lauren classification, tumor location, tumor invasion, or Helicobacter pylori infection was found. In conclusion, the methylation status of the MGMT promoter was related to gastric cancer risk, distant metastasis, and lymph node metastasis, which indicates that MGMT promoter methylation may play an important role in gastric cancer development.

[Brief introduction of ZHENG's "golden hook fishing" technique in acupuncture].

Golden hook fishing technique in acupuncture is one of the characteristics for the inheritance of aca-demic school of ZHENG's acupuncture technique. On the theoretic basis of traditional "lifting and thrusting" technique and "biting hook" sensation, by the coordination of the hands, focusing on the gentle lifting and shaking technique, selecting ashi points, the tendon-knotted sites, the eight influential points and experienced effective points, this special acupuncture technique is used for acute pain disorders and brain disorders in clinical application.

HDAC9 Variant Rs2107595 Modifies Susceptibility to Coronary Artery Disease and the Severity of Coronary Atherosclerosis in a Chinese Han Population.

A previous genome-wide association study showed that a single nucleotide polymorphism (SNP) rs2107595 in histone deacetylase 9 (HDAC9) gene was associated with large artery stroke (LAS) in Caucasians. Based on the similar atherosclerotic pathogenesis between LAS and coronary artery disease (CAD), we aimed to evaluate the associations of SNP rs2107595 with CAD risk and the severity of coronary atherosclerosis in a Chinese Han population, and explore the potential gene-environment interactions among SNP rs2107595 and conventional CAD risk factors. In a two-stage case-control study with a total of 2317 CAD patients and 2404 controls, the AG + AA genotypes of SNP rs2107595 were significantly associated with increased CAD risk (Adjusted odds ratio (OR) = 1.23, Padj = 0.001) and higher modified Gensini scores (Adjusted OR = 1.38, Padj < 0.001). These associations remained significant in subtype analyses for unstable angina pectoris (UAP), non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI). Subgroup and multifactor dimensionality reduction analyses (MDR) further found the gene-environment interactions among SNP rs2107595, body mass index, type 2 diabetes and hyperlipidemia in CAD risk and the severity of coronary atherosclerosis. Moreover, patients with CAD had higher levels of HDAC9 mRNA expression and plasma HDAC9 than controls. Subsequent genotype-phenotype analyses observed the significant correlations of SNP rs2107595 with HDAC9 mRNA expression and plasma HDAC9 levels in controls and patients with NSTEMI and STEMI. Taken together, our data suggest that SNP rs2107595 may contribute to coronary atherosclerosis and CAD risk through a possible mechanism of regulating HDAC9 expression and gene-environment interactions.

Associations of Polymorphisms in MTHFR Gene with the Risk of Age-Related Cataract in Chinese Han Population: A Genotype-Phenotype Analysis.

Homocysteine (Hcy) is a potential risk factor for age-related cataract (ARC). Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme for Hcy metabolism, and variants of MTHFR may affect MTHFR enzyme activity. This study mainly evaluated the associations between variants in MTHFR gene, plasma MTHFR enzyme activity, total Hcy (tHcy) levels and ARC risk in Chinese population. Four single nucleotide polymorphisms (SNPs) in MTHFR gene were genotyped using the high-resolution melting (HRM) method in 502 ARC patients (mean age, 70.2 [SD, 9.0], 46.0% male) and 890 healthy controls (mean age, 67.1 [SD, 11.1], 47.6% male). The plasma MTHFR activity, folic acid (FA), vitamins B12 and B6 levels were detected by enzyme-linked immunosorbent assays (ELISA). The plasma tHcy levels were measured by an automated enzymatic assay. After the Bonferroni correction, the minor allele T of SNP rs1801133 showed a significant association with an increased risk of overall ARC (OR = 1.26, P = 0.003). Consistent association was also found between SNP rs1801133 and cortical ARC risk (OR = 1.44, P = 0.003). Haplotype analyses revealed an adverse effect of the haplotype "C-A-T-C" (alleles in order of SNPs rs3737967, rs1801131, rs1801133 and rs9651118) on ARC risk (OR = 1.55, P = 0.003). Moreover, in a joint analysis of SNPs rs9651118 and rs1801133, subjects with two unfavorable genotypes had a 1.76-fold increased risk of ARC compared with the reference group, and a statistically significant dose-response trend (Ptrend = 0.001) was also observed. Further, in healthy controls and patients with cortical ARC, the allele T of SNP rs1801133 and the increasing number of unfavorable genotypes were significantly correlated with decreased MTHFR activity as well as increased tHcy levels. However, there was no significant association between FA, vitamins B12, B6 levels and MTHFR variants. Our data indicated that variants in MTHFR gene might individually and jointly influence susceptibility to ARC by affecting MTHFR enzyme activity and tHcy levels.