Ischemic stroke is a major public health problem worldwide. Although the circadian clock is involved in the process of ischemic stroke, the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear. In the present study, we determined that environmental circadian disruption (ECD) increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model, by measuring the infarct volume, neurological tests, and angiogenesis-related protein. We further report that Bmal1 plays an irreplaceable role in angiogenesis. Overexpression of Bmal1 promoted tube-forming, migration, and wound healing, and upregulated the vascular endothelial growth factor (VEGF) and Notch pathway protein levels. This promoting effect was reversed by the Notch pathway inhibitor DAPT, according to the results of angiogenesis capacity and VEGF pathway protein level. In conclusion, our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway.
Rats ; Animals ; Vascular Endothelial Growth Factor A/pharmacology* ; Brain Ischemia/metabolism* ; Ischemic Stroke ; Signal Transduction ; ARNTL Transcription Factors/pharmacology* ; Neovascularization, Physiologic/physiology*

Objective:To explore the association between nighttime sleep duration and semen quality.Methods:By using a cross-sectional study, 3357 men were investigated by questionnaire for nighttime sleep duration, the time of falling asleep and falling asleep duration in the Reproductive Center of Shenzhen People's Hospital from August 2017 to August 2018. Semen quality parameters were obtained by computer-aided semen analysis system (CASA). Multiple linear regression was used to analyze the relationship between nighttime sleep duration and semen quality parameters. According to age and body mass index (BMI) stratification, the relationship between nighttime sleep duration and semen quality parameters was further discussed.Results:Compared with males with nighttime sleep duration between 6-8 h, the sperm progressive motility and total motility were 49.15% and 59.49%, respectively, which were significantly lower in the males with nighttime sleep duration≥8 h after adjusting for age, BMI, abstinence time, exercise, drinking and smoking, with regression coefficients, β=-3.16, 95% confidence interval ( CI)=-5.77--0.55 and β=-3.22, 95% CI=-5.93--0.51, respectively. Compared with the shortest duration of falling asleep group (<10 min), the increase of falling asleep duration was related to the decrease of sperm progressive motility ( P=0.045). The total sperm motility of falling asleep duration between 31-60 min group was also significantly lower than that of the shortest falling asleep duration group （ β=-3.80, 95% CI=-6.54--1.06, P=0.007）. Further stratification analysis showed that among the subjects aged 35 to 39 years, the sperm progressive motility of men with nighttime sleep duration less than 6 h was lower than that of 6-8 h group ( β=-4.01, 95% CI=-7.84-0.18, P=0.04). And among the subjects aged more than 40 years, the total sperm number of the men who slept ≥8 h at night was lower than that of the men with nighttime sleep duration between 6-8 h （percentage changes: -47.84%, 95% CI=-72.29%--2.19%, P=0.04）. The progressive and total sperm motility of men with BMI≥24 kg/m 2 and nighttime sleep duration ≥8 h were lower than those with BMI≥24 kg/m 2 in 6-8 h nighttime sleep duration group, and the corresponding regression coefficients were β=-5.75, 95% CI=-10.40--1.10, P=0.02 and β=-6.85, 95% CI=-11.69--2.00, P=0.01. Conclusion:In men ≥40 years old or BMI≥24 kg/m 2, the nighttime sleep duration ≥8 h were associated with the decreased sperm progressive motility and total motility.

Objective:To explore the association between nighttime sleep duration and semen quality.Methods:By using a cross-sectional study, 3357 men were investigated by questionnaire for nighttime sleep duration, the time of falling asleep and falling asleep duration in the Reproductive Center of Shenzhen People's Hospital from August 2017 to August 2018. Semen quality parameters were obtained by computer-aided semen analysis system (CASA). Multiple linear regression was used to analyze the relationship between nighttime sleep duration and semen quality parameters. According to age and body mass index (BMI) stratification, the relationship between nighttime sleep duration and semen quality parameters was further discussed.Results:Compared with males with nighttime sleep duration between 6-8 h, the sperm progressive motility and total motility were 49.15% and 59.49%, respectively, which were significantly lower in the males with nighttime sleep duration≥8 h after adjusting for age, BMI, abstinence time, exercise, drinking and smoking, with regression coefficients, β=-3.16, 95% confidence interval ( CI)=-5.77--0.55 and β=-3.22, 95% CI=-5.93--0.51, respectively. Compared with the shortest duration of falling asleep group (<10 min), the increase of falling asleep duration was related to the decrease of sperm progressive motility ( P=0.045). The total sperm motility of falling asleep duration between 31-60 min group was also significantly lower than that of the shortest falling asleep duration group （ β=-3.80, 95% CI=-6.54--1.06, P=0.007）. Further stratification analysis showed that among the subjects aged 35 to 39 years, the sperm progressive motility of men with nighttime sleep duration less than 6 h was lower than that of 6-8 h group ( β=-4.01, 95% CI=-7.84-0.18, P=0.04). And among the subjects aged more than 40 years, the total sperm number of the men who slept ≥8 h at night was lower than that of the men with nighttime sleep duration between 6-8 h （percentage changes: -47.84%, 95% CI=-72.29%--2.19%, P=0.04）. The progressive and total sperm motility of men with BMI≥24 kg/m 2 and nighttime sleep duration ≥8 h were lower than those with BMI≥24 kg/m 2 in 6-8 h nighttime sleep duration group, and the corresponding regression coefficients were β=-5.75, 95% CI=-10.40--1.10, P=0.02 and β=-6.85, 95% CI=-11.69--2.00, P=0.01. Conclusion:In men ≥40 years old or BMI≥24 kg/m 2, the nighttime sleep duration ≥8 h were associated with the decreased sperm progressive motility and total motility.

Objective: To investigate the inhibitory effect of macrophage foaming by Yinlan Tianzhi formula (YLTZ) and to explain its effects on lipid-induced inflammation and LXRα-ABCA1 signal pathway. Methods: The model of macrophage foaming was induced by incubating the RAW264.7 cells or BMMs with ox-LDL (50 mg·L-1). The serum containing YLTZ was prepared. The cells were divided into blank group, model group, and drug group. After drug intervention, MTT method was used to detect cell proliferation. The lipid accumulation in cells was observed by oil red O staining, and GPO-PAP method was used to determine the total cholesterol content in cells. Protein and mRNA levels were determined by Western blot and RT- qPCR. Results: Compared with control group, after YLTZ treatment, the lipid level was significantly decreased, and the level of mRNA and protein of LXRα and ABCA1 were significant increased. The expression of inflammatory factor COX2 and iNOS was significantly decreased. Conclusion: YLTZ inhibits macrophage foaming through enhancing LXRα-ABCA1 pathway and suppressing of inflammatory response.

AIM To study the effects of No.1 Weiyan Decoction (Codonopsis Radix,Paeoniae Radix alba,Taraxaci Herba,etc.) on hypoxia and hypoxic tolerance in gastric mucosal epithelial cells in rats with precancerous lesion of gastric cancer (PLGC).METHODS Forty rats were randomly divided into normal,model,Vitacoenzyme Tablets and No.1 Weiyan Decoction groups.Except for the normal group,the rats in the other groups were given with N-methyl-N'-nitro-N-nitrosoguanidine and Little Chengqi Decoction to establish a PLGC rat model.Ten weeks after the administration,the gastric mucosal epithelial microvascular ultrastructure was observed,the expressions of Hif1a mRNA,HIF-1 α protein and VEGF protein in gastric mucosal epithelium were detected.RESULTS Compared with the normal group,the number of microvasculatures in gastric mucosal epithelium was decreased;lumen was severely stenosed or expansive;inner wall was not smooth and had adhesion;vascular endothelial cells were swollen;the expression of Hif1α mRNA showed an increasing trend;the expressions of HIF-1α protein and VEGF protein were anomalous in the model group.Compared with the model group,the gastric mucosal vascular lesion of PLGC rats was improved,and the expressions of Hif1a mRNA,HIF-1α protein and VEGF protein were significantly decreased in the No.1 Weiyan Decoction group.CONCLUSION No.1 Weiyan Decoction can improve hypoxia and hypoxia tolerance,and induce angiogenesis in gastric mucosal epithelium in PLGC rats.

This article focused on summarization of the available new screening technology for traditional Chinese medicine (TCM) new drug, including high throughput screening (HTS), biological chip, molecular biological chro-matography, high content screening (HCS), network pharmacology, proteomics, and computer-aided drug design (CADD). And in this review, one example that we applied CADD technology (such as molecular docking, pharma-cophore and molecular similarity) in lipid-lowering TCM new drug development was given. Based on the mechanism of lipid metabolism, CADD technology provided a good method on the prescription optimization and mechanism study. In addition, TCM new drug development proposal which displayed in this paper may provide a useful strategy for screening of TCM new drug.

Objective To evaluate the refinement process for extracting Herba Artemisiae Scopariae(HAS) with macroporous resin.Methods With reservation rate of main peak in the fingerprint as the index,the refinement process for extract of HAS was evaluated.The safety of oral administration of HAS extract before and after refinement process was evaluated by detecting serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST),observing the hepatic histopathological changes in mice model of CCl4-induced acute hepatic injury,and by mice acute toxicity experiment.Results The fingerprint of HAS extract before and after treatment was similar,the difference of their hepatoprotective effect was insignificant,and there was no obvious acute toxic reaction of HAS extract before and after refinement.Conclusion This experiment verified the rationality of the refinement process for extracting Herba Artemisiae Scopariae with macroporous resin by the method of pharmacodynamics combining with HPLC fingerprint.

Objective To investigate the effect of Pericarpium Zanthoxyli (HJ) on guinea pigs trachea in vitro and its therapeutic mechanism. Methods The actions of HJ on the contraction of normal trachea and on the spasm of spasmodic tracheas caused by acetylcholine (Ach) and histamine phosphate (HIS), as well as the actions on intracellular Ca2+ - dependent contraction and extracellular Ca2+ - dependent contraction induced by HIS were observed. Results HJ could inhibit the guinea pigs trachea contraction , antagonize the contraction of trachea spasm induced by Ach and HIS , restrain the extracellular Ca2+ - dependent contraction induced by HIS in a dose- dependent manner. Conclusion HJ has an antiasthma effect.

Objective To compare the therapeutic effect of Qingre Anchuang Tablets(QAT) processed by new or old technology on rabbit ear acne.Methods Experimental rabbit ear acne was induced by coal tar.After the modeling,the rabbits were administrated with QAT processed by new or old technology.The thickness,weight and PGE2 level of the acne ear were measured,and the pathological changes of the acne ear were also examined.Results QAT processed by new or old technology could decrease the thickness,weight and PGE2 level of the ear significantly,and relieve the pathological changes of the acne ear.The effects of QAT processed by new technology was better than that of QAT processed by old technology.Conclusion QAT processed by new technology has a better therapeutic effect on rabbit ear acne than QAT processed by old technology.