Common susceptibility variants of KDR and IGF-1R are associated with poststroke depression in the Chinese population.

Background: Depression, one of the most frequent complications after stroke, increases the disease's burden and physical disability. Poststroke depression (PSD) is a multifactorial disease with genetic, environmental and biological factors involved in its occurrence. Genetic studies on PSD to date have mainly focused on the monoamine system and brain-derived neurotrophic factors. However, understanding is still limited about the influence of the single nucleotide polymorphism (SNP) of other neurotrophic factors on PSD. Aims: The present study aimed to investigate the relationship between seven vascular endothelial growth factor (VEGF) family gene variants that occur with PSD. Methods: A multicentre candidate gene study from five hospitals in Jiangsu Province from June 2013 to December 2014 involved 121 patients with PSD and 131 patients with non-PSD. Demographic characteristics and neuropsychological assessments were collected. The χ2 test was used to evaluate categorical variables, while the independent t-test was applied to continuous variables. SNPs in seven genes (VEGFA, VEGFB, KDR, FLT-1, IGF-1, IGF-1R and PlGF) were genotyped. Single-marker association for PSD was analysed by χ2 tests and logistic regression using SPSS and PLINK software. Results: Patients with PSD included more women and those with lower education levels, lower body mass indexes, lower Mini-Mental State Examination scores, and higher scores on the 17-item Hamilton Depression Rating Scale than non-PSD patients. Ninety-two SNPs with seven genes were genotyped and passed quality control. The rs7692791 CC genotypes, the C allele of KDR and the rs9282715 T allele of IGF-1R increased the risk for PSD (χ2=7.881, p=0.019; χ2=4.259, p=0.039; χ2=4.222, p=0.040, respectively). In addition, the SNP rs7692791 of KDR was significantly associated with PSD by the logistic regression of an additive model (p=0.015, OR=9.584, 95% CI: 1.549 to 59.31). Conclusions: Patients with rs7692791 C allele carriers or the CC genotype of KDR and the rs9282715 T allele of IGF-1R may have PSD susceptibility. Findings such as these may help clinicians to identify the high-risk population for PSD earlier and, thus, enable them to provide more timely interventions. Trial registration number: ChiCTR-OCH-13003133.

Relationship Between Red Blood Cell Distribution Width and All-Cause Mortality in Disseminated Intravascular Coagulation Patients: A Retrospective Analysis.

PURPOSE: Studies regarding death risk factors of disseminated intravascular coagulation (DIC) patients were limited. We conducted this study to investigate whether red blood cell distribution width (RDW) was independently related to all-cause mortality of DIC patients. METHODS: We used data from the Medical Information Mart for Intensive Care III version 1.4 (MIMIC-III v1.4). A total of 2098 patients with DIC were included. The main outcome was in-hospital all-cause mortality. RESULTS: After adjusting for potential covariates, the in-hospital all-cause mortality was positively correlated with RDW. The hazard ratio (HR), 95% confidence intervals (CI), and P-value were 1.08, (1.05, 1.12), and P<0.0001, respectively. The Kaplan-Meier curve found DIC patients with elevated RDW had a lower survival rate than patients with normal RDW (P<0.0001). A nonlinear relationship between RDW and mortality was found with the inflection point 19.2%. When RDW <19.2%, RDW was positively correlated with in-hospital all-cause mortality of DIC patients (HR (95% CI): 1.17 (1.11, 1.24), P<0.0001). An elevation in RDW greater than 19.2% did not result in an additional increased risk of mortality (HR=0.97, 95% CI: 0.91-1.04, P=0.4617). CONCLUSION: RDW is an independent predictor of all-cause mortality in DIC patients. Furthermore, there is a nonlinear association between RDW and all-cause mortality of DIC patients.

The Association Between Serum Anion Gap and All-Cause Mortality in Disseminated Intravascular Coagulation Patients: A Retrospective Analysis.

PURPOSE: Studies regarding death risk factors of disseminated intravascular coagulation (DIC) patients were limited. Therefore, we conducted this study to investigate whether the serum anion gap (AG) was independently related to all-cause mortality of DIC patients. METHODS: We used the data from Medical Information Mart for Intensive Care III version 1.4 (MIMIC-III v1.4). A total of 2,654 DIC patients were included. The main outcomes were in-hospital, 30-day, and 90-day all-cause mortality. The AG was measured upon ICU admission and its association with mortality was evaluated using the Cox proportional-hazards regression model. The generalized additive model and the smooth curve fitting were introduced to examine the non-linear association. RESULTS: After adjusting for potential covariates, the in-hospital, 30-day, and 90-day all-cause mortality were positively correlated with AG. The hazard ratio (HR), confidence intervals (CI), and P were 1.05 (1.04-1.07) <0.0001, 1.06 (1.04-1.07) <0.0001, and 1.05 (1.03-1.07) <0.0001, respectively. We did not find an obvious non-linear relationship between AG and in-hospital, 30-day, and 90-day mortality, which indicated that the association between AG and all-cause mortality of DIC patients was nearly linear. CONCLUSION: Serum AG is positively related with all-cause mortality in DIC patients.

Escitalopram improves neural functional prognosis and endothelial dysfunction in patients with acute cerebral infarction.

BACKGROUND: Escitalopram is one of the most commonly used SSRIs at present, which has the characteristics of quick onset, less interactions with other drugs, and relative safety. OBJECTIVE: This study aims to investigate the effects of escitalopram on neural functional prognoses and endothelial dysfunction after acute ischemic stroke. METHODS: One hundred eligible patients afflicted with acute ischemic stroke were randomized into two groups: control and treatment groups. Patients in the treatment group received escitalopram in addition to the basic therapies in the control group over a period of 90 days. Neurological deficits were quantified using the National Institutes of Health Stroke Scale (NIHSS) score and Barthel index (BI) score, cognitive impairment was determined using the Mini-Mental State Examination (MMSE) score, depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (HAMD). Furthermore, post-stroke depression (PSD) was defined based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), with a HAMD score ≥17. Flow-mediated vascular dilatation (FMD) of the brachial artery was use as a surrogate indicator for endothelial dysfunction assessment with ultrasound. RESULTS: The mean NIHSS and HAMD scores on day 90 after treatment were significantly lower in the treatment group than in the control group (2.17±0.36 vs. 4.24±0.85; 5.81±1.35 vs. 10.43±4.91; P < 0.01), while the mean BI score and FMD were significantly higher in the treatment group (93.08±6.23 vs. 79.64±7.56, P < 0.01; 8.71±2.35 vs. 5.83±1.21, P < 0.05) than in the control group. The improvement in MMSE score was not significantly different between the two groups. CONCLUSIONS: Treatment with escitalopram early after ischemic stroke can improve neural functional prognoses and endothelial dysfunction. Escitalopram had less side effects, which is worthy of clinical prophylactic application.

Effects of the prophylactic use of escitalopram on the prognosis and the plasma copeptin level in patients with acute cerebral infarction.

This study aimed to investigate whether the routine administration of escitalopram for three months would improve the prognosis of patients with ischemic stroke and decrease the plasma copeptin level. A total of 97 patients with acute cerebral infarction were randomly allocated to receive escitalopram (5-10 mg once per day, orally; n=49) or not to receive escitalopram (control group; n=48) for 12 weeks starting at 2-7 days after the onset of stroke. Both groups received conventional treatments, including physiotherapy and secondary prevention of stroke. The National Institutes of Health Stroke Scale (NIHSS) score was used to evaluate the disability of patients at the initial evaluation and at the monthly follow-up visits for three months. Impairment in the daily activities was assessed using the Barthel Index (BI), while cognitive impairment was assessed using Mini-Mental State Examination (MMSE) score. The psychiatric assessment included the administration of the Present State Examination modified to identify Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) symptoms of depression. The severity of depression was measured using the 17-item Hamilton Rating Scale for Depression (HAMD). During the 3-month follow-up period, 95 patients were included in the analysis (two patients withdrew from the escitalopram group). NIHSS and BI improvement at the 90th day were significantly greater in the escitalopram group (P<0.05), while HAMD and plasma copeptin levels significantly decreased, compared to the control group (P<0.01). In patients with acute ischemic stroke, the earlier administration of escitalopram for three months may improve neurological functional prognosis and decrease copeptin level.

Effects of the prophylactic use of escitalopram on the prognosis and the plasma copeptin level in patients with acute cerebral infarction

This study aimed to investigate whether the routine administration of escitalopram for three months would improve the prognosis of patients with ischemic stroke and decrease the plasma copeptin level. A total of 97 patients with acute cerebral infarction were randomly allocated to receive escitalopram (5-10 mg once per day, orally; n=49) or not to receive escitalopram (control group; n=48) for 12 weeks starting at 2-7 days after the onset of stroke. Both groups received conventional treatments, including physiotherapy and secondary prevention of stroke. The National Institutes of Health Stroke Scale (NIHSS) score was used to evaluate the disability of patients at the initial evaluation and at the monthly follow-up visits for three months. Impairment in the daily activities was assessed using the Barthel Index (BI), while cognitive impairment was assessed using Mini-Mental State Examination (MMSE) score. The psychiatric assessment included the administration of the Present State Examination modified to identify Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) symptoms of depression. The severity of depression was measured using the 17-item Hamilton Rating Scale for Depression (HAMD). During the 3-month follow-up period, 95 patients were included in the analysis (two patients withdrew from the escitalopram group). NIHSS and BI improvement at the 90th day were significantly greater in the escitalopram group (P<0.05), while HAMD and plasma copeptin levels significantly decreased, compared to the control group (P<0.01). In patients with acute ischemic stroke, the earlier administration of escitalopram for three months may improve neurological functional prognosis and decrease copeptin level.

Efficacy and Safety of Once-Weekly versus Twice-Weekly Bortezomib in Patients with Hematologic Malignancies: A Meta-analysis with Trial Sequential Analysis.

STUDY OBJECTIVE: To compare the efficacy and safety of once-weekly and twice-weekly bortezomib therapy in patients with hematologic malignancies. DESIGN: Meta-analysis of 13 clinical or randomized controlled trials, with trial sequential analysis (TSA). PATIENTS: A total of 1567 patients with hematologic malignancies who received either once-weekly or twice-weekly bortezomib therapy. MEASUREMENTS AND MAIN RESULTS: We conducted a comprehensive literature search of the PubMed, EMBASE, and Cochrane Library databases. A meta-analysis was conducted to calculate the pooled effect size; TSA was performed to assess the reliability of the pooled results. The pooled risk ratio (RR) for the overall response rate (ORR) was 1.00 (95% confidence interval [CI] 0.77-1.29, p=0.99), indicating no significant differences between patients who received once-weekly bortezomib and those who received twice-weekly bortezomib. TSA showed that the cumulative Z-curve of the ORR entered the futility area, implying that reliable evidence was obtained for this pooled result. The pooled RR for any grade of peripheral neuropathy was 0.48 (95% CI 0.26-0.88, p=0.02); however, the TSA plot revealed that there was insufficient evidence for this result. The pooled RR for peripheral neuropathy grade 3 or higher was 0.21 (95% CI 0.13-0.34, p<0.00001), and reliable evidence was obtained according to TSA. Regarding the other toxicities, including anemia, thrombocytopenia, neutropenia, infection, diarrhea, constipation, nausea, vomiting, and fatigue, we did not find any significant differences between patients who received once-weekly bortezomib and those who received twice-weekly bortezomib. CONCLUSION: Compared with twice-weekly bortezomib, once-weekly bortezomib had a comparable ORR and a probable lower incidence of peripheral neuropathy. More clinical trials are needed to draw a conclusion regarding the difference in peripheral neuropathy between the two groups because of the insufficient evidence detected by TSA and the inconsistent results among subgroups.

Efficacy and safety of subcutaneous versus intravenous bortezomib in multiple myeloma: a meta-analysis
.

PURPOSE: We performed this meta-analysis to compare the efficacy and safety between two different administration routes of bortezomib, subcutaneous and intravenous. METHODS: Six retrospective studies and three randomized controlled trials (RCTs) were included in our study. Data from retrospective studies or RCTs were pooled and displayed in their corresponding subgroup, retrospective studies subgroup or RCTs subgroup. We comprehensively compared the overall response rate (ORR) and the incidence of adverse events between subcutaneous and intravenous bortezomib. RESULTS: We did not find statistical difference in ORR between the two administration routes. The pooled RRs for ORR were 0.99 (95% CI = 0.79 - 1.25, p = 0.95; retrospective studies subgroup) and 1.02 (95% CI = 0.93 - 1.11, p = 0.69; RCTs subgroup). Compared with intravenous bortezomib, the subcutaneous bortezomib reduced the incidence of peripheral neuropathy, both any grade and grade ≥ 3. The pooled RRs for any grade of peripheral neuropathy were 0.33 (95% CI = 0.15 - 0.71, p = 0.004; retrospective studies subgroup) and 0.55 (95% CI = 0.31 - 0.97, p = 0.04; RCTs subgroup), and for peripheral neuropathy grade ≥ 3 were 0.40 (95% CI = 0.16 - 0.95, p = 0.04; retrospective trials subgroup) and 0.39 (95% CI = 0.19 - 0.80, p = 0.01; RCTs subgroup). Only retrospective trials subgroup found that the incidence of thrombocytopenia and renal and urinary disorders were lower in subcutaneous bortezomib than in intravenous, with the pooled RRs 0.46 (95% CI = 0.29 - 0.72, p = 0.0007; retrospective trials subgroup) and 0.23 (95% CI = 0.09 - 0.56, p = 0.001; retrospective trials subgroup), respectively. The RCTs subgroup did not find statistical differences in these two adverse events. CONCLUSIONS: Subcutaneous bortezomib did not significantly reduce therapeutic efficacy but resulted in a lower incidence of peripheral neuropathy than intravenous bortezomib. Compared with intravenous bortezomib, subcutaneous bortezomib might reduce the incidence of thrombocytopenia and renal and urinary disorders, but this needs more clinical trials to confirm.
.

Leojaponic acids A and B, two new homologous terpenoids, isolated from Leonurus japonicus.

The present study aimed at isolation and purification of the bioactive terpenoids from the herb of Leonurus japonicus by chromatographic separations such as silica gel, sephadex LH-20 and C18 reversed phase silica gel, as well as preparative HPLC. As a result, leojaponic acids A (1, C17H24O4) and B (2, C18H26O4), two homologous terpenoids, together with (-)-loliolide (3), 1-(3-ethylphenyl) ethane-1, 2-diol (4) and dibutyl phthalate (5), were isolated from the EtOH extract of L. japonicus. All the chemical structures of the isolates were elucidated on the basis of 1D and 2D NMR analyses. Compounds 1 and 2 were new terpenoids, and Compounds 3 and 4 were isolated and identified for the first time from this plant. In addition, the α-glucosidase and tyrosinase inhibitory activity of the new compounds were evaluated.

[miR-328 Inhibits K562 Cell Proliferation by Up-regulation of C/EBPα Expression].

OBJECTIVE: Our research was aim to investigate the effect of microRNA-328 (miR-328) on proliferation of chronic myeloid leukemia(CML) cell K562 and the mediated effect of C/EBPα. METHODS: The eukaryotic expression vectors of miR-328 targeting gene and suppressor gene (hsa-miR-328 and hsa-miR-328-inhibitor) were constructed, and transfected into K562 cells respectively. The mRNA expression levels of miR-328 and C/EBP α were detected by real-time fluorescence quantitative RT-PCR; C/EBP α protein expression was detected by Western blot; CCK-8 was used to estimate the cell viability. RESULTS: The recombinant genes of hsa-miR-328 and hsa-miR-328-inhibitor were successfully constructed and transfected into K562 cells. Fluorescent cells were observed after 24 h, and the visible fluorescence cells were gradually increased after 48 h or 72 h, the miR-328 showed no effect on the mRNA expression of C/EBPα detected by RT-PCR. Meanwhile, miR-328 showed recovering effect on C/EBPα translation and inhibition of K562 cells proliferation. CONCLUSION: miR-328 has been successfully constructed and transfected into K562 cells, miR-328 inhibits the proliferation of K562 cells by up-regulation of C/EBPα.

Association between the 5-HTR1B gene polymorphisms and alcohol dependence in a Han Chinese population.

The human serotonin receptor 1B (HRT1B) plays an important role in regulating serotonin release. Previous research has suggested that the genetic variation of the HTR1B gene may confer susceptibility to alcoholism or some subtypes of alcohol dependence, but the evidence has been inconsistent. The aim of the present study is to examine whether polymorphic variants of the HTR1B gene are associated with alcohol dependence subtypes or drinking-related behaviors in Chinese Han population. Alcohol-dependent (AD) male patients (n=135) and controls (n=143) were genotyped for two polymorphisms: A161T in the promoter region and the synonymous variation G861C in the coding region of HTR1B. The results showed that the A161T polymorphism was associated with alcohol dependence (T vs. A allele: p=0.002; OR=2.18, 95% CI: 1.32-3.60). This association was strengthened in those with positive family history (OR=3.12, 95% CI: 1.71-5.70) and/or early onset (OR=4.53, 95% CI: 2.18-9.44) of alcohol dependence. The A161T variant was also significantly associated with age of onset of alcoholism (p=0.001). Furthermore, there was a significant difference of haplotypic frequencies between patients and controls (χ(2)=14.84, df=3, p=0.002), with one common haplotype AG of being significantly underrepresented among the patient group compared to the control group (34% vs. 47.7%, permutation p=0.0034; OR=0.56; 95% CI: 0.39-0.79). These findings confirm HTR1B as a susceptibility gene for alcohol dependence in the sample of Chinese Han population. The HTR1B A-161T polymorphism may be particularly valuable as a functional genetic marker for alcoholism and merits additional study.

[Effects of electroacupuncture plus oxygenmedicine on the expression of Bcl-2 and Bax proteins in the hippocampal CA 1 area in rats with global cerebral ischemia/reperfusion injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) plus oxygenmedicine (OM) on the expression of Bcl-2 and Bax in the hippocampal CA 1 area in cerebral ischemia/reperfusion injury (CI/RI) rats. METHODS: Thirty SD rats were randomized into sham-operation, model, EA, OM, EA+OM groups (n=6 /group). CI/RI model was established by using modified Pulsinelli 4 vessel occlusion and reperfusion. EA (100 Hz, 3.5 mA) was applied to "Baihui" (GV 20) and "Zusanli" (ST 36) 30 min, once daily for 4 days. Rats of OM and EA+ OM groups were put into a box filled with oxygen and atomized herbal medicines containing Bingpian (Borneolum), Shexiang (Moschus), Huangjing (Rhizoma Polygonati), Shouwu (Radix Polygoni Multiflori), etc. for 30 min, once daily for 4 days. Bcl-2 and Bax expression of the hippocampal CA 1 area was detected by immunohistochemistry. RESULTS: Compared with sham group, the numbers of Bcl-2 immunoreaction (IR) and Bax IR positive cells, and the immunoactivity of Bcl-2 IR and Bax IR positive products in the hippocampal CA 1 area were increased significantly in model group (P < 0.05, P < 0.01). In comparison with model group, the number of Bcl-2 IR positive cells and Bcl-2 immunoactivity in EA, OM and EA+OM groups increased considerably (P < 0.01), while Bax IR positive cell numbers and Bax immunoactivity in EA, OM and OM+ EA groups decreased significantly (P < 0.01). The effects of EA+ OM were significantly superior to those of EA and OM groups in upregulating Bcl-2 IR positive cell number and Bcl-2 immunoactivity and downregulating Bax IR positive cell number and Bax immunoactivity (P < 0.01). No significant differences were found between EA and OM groups in the abovemen-EA and OM and EA+OM can effectively regulate the expression of Bcl-2 and Bax in tioned indexes (P > 0.05). CONCLUSION: EA and OM and EA + OM can effectively regulate the expression of Bcl-2 and Bax in the hippocampal CA 1 area in CI/RI rats, and the effects of EA+OM are significantly superior to those of simple EA and simple OM, which may contribute to their effect in improving cerebral ischemia.