Objective To investigate the effects of Kr üppel-like factor 2 ( KLF2 ) on oxidized low density lipoprotein (ox-LDL) induced expression of microRNA-146a (miR-146a) and proinflammatory cyto-kines (MCP-1 and IL-6) in human umbilical vein endothelial cells (HUVECs).Methods Human umbili-cal vein endothelial cells (HUVECs) were cultured and then stimulated with 50μg/ml ox-LDL for 24 hours. HUVECs were infected with adenovirus vectors over-expressing human KLF2 at an appropriate multiplicity of infection.KLF2-siRNA duplexes were transfected into HUVECs to silence the gene expression .HUVECs were collected at time points of 0 h, 3 h, 6 h, 12 h, 24 h and 48 h after infection.Real-time quantitative-PCR was performed to measure the expression of miR-146a at mRNA level.Silenced endogenous miR-146a using LNA-anti-miR-146 a was transfected into HUVECs with lipofectamine 2000 .The levels of MCP-1 and IL-6 in supernatants were detected by ELISA .Results KLF2 remarkably inhibited the expression of miR-146 a in unstimulated and ox-LDL-stimulated HUVECs in a time-dependent manner .The ox-LDL induced ex-pression of miR-146a, MCP-1 and IL-6 in HUVECs were significantly decreased by KLF2.Silenced expres-sion of miR-146a downr-egulated the ox -LDL induced expression of MCP-1 and IL-6 in HUVECs.Moreover, silenced miR-146 a could partly reverse the inhibitory effects of KLF 2 on ox-LDL induced expression of MCP-1 and IL-6 in HUVECs.Conclusion KLF2 inhibited ox-LDL induced expression of MCP-1 and IL-6 in HUVECs partly through down-regulating the expression of miR-146a.

Crohn's disease (CD) is a chronic and progressive disease which can affect the whole digestive tract and associate with extraintestinal manifestations. The incidence and prevalence of CD increased rapidly in China in recent years. Understanding the natural history of CD is of great significance for disease risk stratification, treatment decision and prognosis judgement. This article reviewed the global evolution of epidemiology and natural history of CD, the predictive factors of natural history and the therapeutic interventions which may alter the natural history of CD.

Objective To investigate the effect of cluster needling at scalp points plus gavage of modified Buyang Huanwu decoction on NSC differentiation in rats with ischemic stroke of qi deficiency and blood stasis type.Methods A model of qi deficiency and blood stasis syndrome was made using healthy rats. Dil dye was given for pre-labelling after the success of model making. The rats were randomized into groups A, B, C, D, E and F. Group F consisted of 4 rats and each of the other groups, of 12 rats. A rat model of ischemic stroke of qi deficiency and blood stasis type was made by MCAO at 48 hrs after pre-labelling. After the success of model making, group A was the model group, group B was treated by cluster needling at scalp points, group C was treated by an oral gavage of Buyang Huanwu decoction, group D was treated by an oral gavage of modified Buyang Huanwu decoction, group E was treated by cluster needling at scalp points plus an oral gavage of modified Buyang Huanwu decoction and group F was the sham operation group. The rats were sacrificed at various time points respectively and the materials were taken. By nerve function assessment, double immunofluorescence staining and laser scanning confocal microscopy, a comparative study was conducted to investigate the effects of different treatments on NSC differentiation.Results There was a statistically significant difference in the nerve function score between group B, C, D, E or F and group A after one week of treatment (P<0.01), between group B or E and group A after two weeks of treatment (P<0.05,P<0.01) and between group E and group C or D after one and two weeks of treatment (P<0.01,P<0.05). After one and two weeks of treatment, there were statistically significant differences in Brdu﹢/NeuN﹢ cell count, Brdu﹢/GFAP﹢ cell count, Dil﹢/Brdu﹢NeuN﹢ cell count and Dil﹢/Brdu﹢/GFAP﹢ cell count between group B, C, D or E and group A (P<0.01), between group D or E and group B or C (P<0.01) and between groups E and D (P<0.01).Conclusions Various treatments have a promoting effect on nerve stem cell differentiation in the rats. Of various treatments, cluster needling at scalp points plus gavage of modified Buyang Huanwu decoction has the best therapeutic effect.

Objective To investigate the expression of serum 25(OH)D,vitamin D receptor (VDR)and vitamin D1-α hydroxylase (CYP27B1) in intestinal mucosa tissues of patients with inflammatory bowel disease (IBD).Methods From January 1st to December 31st in 2014,105 patients with IBD were enrolled,among them there were 49 cases of ulcerative colitis (UC) and 56 cases of Crohn's disease (CD);there were 20 cases in remission,26 cases in mild active phase,37 cases in moderate active phase and 22 cases in severe active phase;and 50 cases with lesions located in the left colon and 55 cases with lesions located in the right colon.At the same period,45 healthy individuals were also recruited as controls,whom were suspected as IBD but at last proved healthy.The lactulose and mannitol absorption ratio (LMR),serum endotoxin,tumor necrosis factor-α (TNF-α) and 25(OH)D levels,and the expressions of VDR and CYP27B1 in the intestinal mucosa tissues were detected in all the subjects.T test,one-way analysis of variance and chi square test were used for statistical analysis.Results The LMR,endotoxin and TNF-α levels of UC group were (63.2 ± 13.9)％,(118.9 ± 19.7) EU/mL,and (109.6 ± 18.4) ng/L,respectively,which were higher than those of the healthy control group ((3.3 ± 1.2)％,(34.2 ±5.6) EU/mL,and (0.6±0.3) ng/L);the level of 25 (OH)D was (36.6± 9.7) nmol/L,which was lower than that of healthy control group ((49.6± 10.9) nmol/L),and all the differences were statistically significant (t =28.796,29.284,27.817 and 6.118,all P＜0.05).LMR,endotoxin and TNF-α levels of CD group were (52.9±11.3)％,(96.4±10.6) EU/mL and (83.0±16.1) ng/L,respectively,which were higher than those of the healthy control group,25(OH)D level was (44.4±9.4) nmol/L,which was lower than that of healthy control group,and all the differences were statistically significant (t=34.555,39.716,34.293 and 0.012,all P＜0.05).The differences in LMR,endotoxin,TNF-α and 25 (OH)D levels among healthy control group,remission group,mild active group,moderate active group and severe active group were statistically significant (F=286.731,385.690,657.830 and 18.932,all P＜0.01) which was dependent on the disease activity.Compared with those of the healthy controls,the levels of LMR,endotoxin and TNF-α of the left colon group and the right colon group increased,and 25(OH)D levels decreased.The high expression rates of VDR in UC group and CD group were 36.7％ (18/49) and 55.4％ (31/ 56),respectively,which were both lower than that of healthy control group (80.0％ (36/45)),and the differences were statistically significant (x2 =38.574 and 13.837,both P＜0.05).The high expression rates of CYP27B1 of UC group and CD group were 26.5％ (13/49) and 35.7％ (20/56),respectively,which were both higher than that of healthy control group (22.2％ (10/45)),and the differences were statistically significant (x2=6.499 and 4.430,both P＜0.05).The differences in the high expression rates of VDR and CYP27B1 among healthy control group,remission group,mild active group,moderate active group and severe active group were statistically significant (F=33.470 and 27.142,both P＜0.01),which was dependent on the disease activity.Compared with that of the healthy control group,the high expression rates of VDR of the left colon group and the right colon group decreased,and the high expression rates of CYP27B1 increased.Conclusion There is vitamin D metabolic imbalance in IBD patients,as well as low serum 25(OH)D level,low rate of high VDR expression in colonic mucosa tissues and high rate of high CYP27B1.

Purpose: No consensus exists about the causal relationship between vitamin D (VD) and male factor infertility due to heterogeneity and confounding factors even in randomized controlled trials (RCTs). This study aimed to investigate the causal association between 25 hydroxyvitamin D (25OHD) levels and male factor infertility through Mendelian randomization (MR) and provide complementary information for optimization of future RCTs. Materials and Methods: Two-sample MR analyses with four steps were performed. Single-nucleotide polymorphisms (SNPs) for VD were extracted from 417,580 Europeans in the UK Biobank, and the summary-level data of male factor infertility (825 cases and 85,722 controls) were extracted from the FinnGen. Results: Totally 99 SNPs robustly associated with the 25OHD were included, and a 1-unit increase in genetically predicted natural-log transformed 25OHD levels was associated with decreased risk of male factor infertility (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.44–0.89; p=0.010), which was consistent in all three sensitivity analyses (MR-Egger, weighted median, and weighted mode methods). The conclusion still stands after removing SNPs which explained more variation in the male factor infertility than the 25OHD (OR, 0.61; 95% CI, 0.42–0.88; p=0.009; n=62), and which were associated with confounders (body mass index, type 2 diabetes, smoking, and coronary artery diseases) of male factor infertility (OR, 0.58; 95% CI, 0.39–0.85; p=0.005; n=55). Conclusions VD supplement to increase serum 25OHD levels may be clinically beneficial for male factor infertility in the general population. The well-designed RCTs should be performed in priority to address this question.

This study was designed to detect the impact of Valerian Ligusticum Pill (VLP) on cerebral ischemia reperfusion injury in rats, and explore the mechanism of angiogenesis. Sixty SD male rats were randomly divided into five groups, including sham operation group, model group, VLP-low (30mg·kg^-1) group, VLP-high (50mg·kg^-1) group and nimodipine (10mg·kg^-1) group. The ischemia reperfusion injury model was induced by occlusion of middle cerebral artery with suture embolus, reperfusion after 30 minutes' ischemia. When the rats were awake, the first neurological function scores was determined with modified neurological severity score (mNSS). The rats were given VLP (30mg·kg^-1, 50mg·kg^-1) and nimodipine (10mg·kg^-1) through intragastric administration at 2 mL, once a day for a total of 7 days, while an equal amount of distilled water was used in the sham operation group and model control group. After 7 days, the rats were given second neurological function scores, and improvement of neurological function=[the first score]-[the second score]. The rats were sacrificed to investigate the infarction volume percentage with 2,3,5-triphenyl tetrazolium chloride method; do the qualitative and half quantitative analyses for protein vascular endothelial growth factor receptor 2 (VEGFR2) in the tissue of cortex infarction around by Western blot; detect the new blood vessels of cortex infarction around by ki67/lectin immunofluorescence double staining method. Results suggest that VLP could significantly improve the neurological function, reduce the percentage of infarct volume, increase the expression of VEGFR2 and number of new blood vessels in the cortex infarction around compared with model group. In conclusion, VLP may relive the acute cerebral ischemia reperfusion injury in rats by inducing angiogenesis.

Objective:To analyze the correlation between sleep midpoint and sleep quality in insomnia patients with type 2 diabetes mellitus (T2DM).Methods:By adopting current situation investigation research, total of 150 T2DM patients hospitalized in the Department of Endocrinology, the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from November 2021 to July 2022 were selected as the research objects. The general information questionnaire, Pittsburgh Sleep Quality Index (PSQI), anxiety scale (SAS) and Depression Scale (SDS) were used to investigate, and then analysis the datum.Results:Among 150 T2DM insomnia patients, 41 cases (27.33%) were in the early midpoint sleep group, 37 cases (24.67%) were in the middle midpoint sleep group, and 72 cases (48.00%) were in the late midpoint sleep group. There were significant differences in the distribution of sex, age and BMI level among different sleep midpoint groups ( χ2=7.24, 13.36, 15.93, all P<0.05). The scores of time to fall asleep at the midpoint of sleep in the 3 groups were (2.12 ± 1.25), (2.65 ± 0.79), (2.33 ± 1.02), the difference was significant ( F=2.14, P<0.05); the daytime disability scores in the 3 groups were (1.39 ± 1.36), (2.16 ± 1.12), (1.85 ± 1.32), the difference was significant ( F=3.17, P<0.05). Logistic regression analysis of disorder showed that the time to fall asleep ( OR=4.922, P<0.05) and daytime disability ( OR=4.043, P<0.05) had significant influence to the middle midpoint of sleep group when the early midpoint of sleep group as the control, while the male ( OR=2.182, P<0.05), 50 - 70 years old ( OR=5.005, P<0.05) and BMI over fat side ( OR=3.488, P<0.05) had significant influence to the late midpoint of sleep group. Conclusions:Medical staff should pay attention to the sleep quality of T2DM patients, pay attention to the sleep midpoint of patients, and improve patients′cognition of healthy sleep patterns.

Objective To analyze clinicopathological characteristics and the potential risk-related factors of female breast hyperplasia in different age groups.Method From Jan 2015 to Dec 2016,patients diagnosed with breast hyperplasia in 12 hospitals were evaluated.All patients completed the self-designed questionnaires on women'health,including basic demographic information,clinic examination information,radiologic information and pathologic results.The patients were divided into a young group (＜ 45 years old) and an elderly group (from 45 to 75 years old).Results There were 3 684 cases of breast hyperplasia,including 2 291 cases in young group and 1 393 cases in elder group,respectively Clinically breast pain type were most commonly observed in both young and older groups (50.3％ vs.42.7％,P ＜ 0.001).While pathological research based on biopsy showed that breast adenopathy were the most common changes in both groups (67.9％ vs.61.7％,P ＜0.001).More breast cancer cases were identified in elder group than that in young group,especially in clinically lump type patients (9.4％ vs.4.2％,P ＜ 0.001).Compared with elder group,patients in young group have different distribution characteristics regarding to fertility factors,lifestyle factors and psychology scale including anxiety and depression.Conclusion Distributions of clinicopathological characteristics and risk factors of female breast hyperplasia differ across different age groups.

Hyperhomocysteinemia (Hhcy) is an independent risk factor for Alzheimer's disease (AD), and insulin-resistance is commonly seen in patients with Hhcy. Liraglutide (Lir), a glucagon-like peptide that increases the secretion and sensitivity of insulin, has a neurotrophic or neuroprotective effect. However, it is not known whether Lir ameliorates the AD-like pathology and memory deficit induced by Hhcy. By vena caudalis injection of homocysteine to produce the Hhcy model in rats, we found here that simultaneous administration of Lir for 2 weeks ameliorated the Hhcy-induced memory deficit, along with increased density of dendritic spines and up-regulation of synaptic proteins. Lir also attenuated the Hhcy-induced tau hyperphosphorylation and Aβ overproduction, and the molecular mechanisms involved the restoration of protein phosphatase-2A activity and inhibition of β- and γ-secretases. Phosphorylated insulin receptor substrate-1 also decreased after treatment with Lir. Our data reveal that Lir improves the Hhcy-induced AD-like spatial memory deficit and the mechanisms involve the modulation of insulin-resistance and the pathways generating abnormal tau and Aβ.

Objective:To investigate the relationship between single nucleotide polymorphism (SNPs) of Zeste homolog enhancer 2 (EZH2) gene and the risk of breast cancer.Methods:Recruiting 1 039 breast cancer patients and 1 040 controls at 22 referral hospitals nationwide in China, the genotype distribution of 3 SNPs loci of EZH2 genes was observed to detect the correlation between different genotypes and the risk of breast cancer genotypes EZH2 expression in breast cancer tissues and its correlation with patient prognosis were analyzed using breast cancer data from the database.Results:EZH2 rs6464926 CC genotype was compared with TT genotype (TT vs. CC: OR=1.362, 95% CI: 1.063-1.746, P=0.015) and dominant model (TC+TT vs .CC: OR=1.22, 95% CI: 1.004-1.483, P=0.045) .In women with BMI ≥24 kg/m 2, the TC genotype ( P=0.050), TT genotype ( P=0.025) and dominant model (TC+TT, P=0.021) of rs6464926 locus were significantly different from CC genotype in cancer risk. rs6464926 was correlated with EZH2 gene expression ( P=6.89E-47). EZH2 gene is highly expressed in breast cancer tissues, and patients with high expression were associated with shorter OS ( HR=1.27, P=0.013), DMFS ( HR=1.37, P<0.01), and RFS ( HR=1.44, P<0.01). Conclusions:The polymorphism rs6464926 of EZH2 gene is associated with breast cancer susceptibility in Chinese women. rs6464926 might regulate breast cancer risk and prognosis by changing EZH2 expression.