OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Stroke， including ischemic stroke and hemorrhagic stroke， has the characteristics of high morbidity， high disability rate， high mortality rate， high recurrence rate， and high economic burden. Ischemic stroke is the most common type of stroke， which is mainly caused by intracranial artery occlusion. The clinical manifestations of patients are hemiplegia， aphasia， sensory disturbance， and other neurological deficits， accompanied by gastrointestinal symptoms such as constipation and gastrointestinal bleeding. Intestinal flora plays an important role in the pathogenesis of ischemic stroke， and its potential biological effects have received extensive attention. Intestinal flora can not only affect intestinal barrier function but also regulate gastrointestinal immunity and affect host homeostasis. In recent years， traditional Chinese medicine （TCM） has shown remarkable effects and small adverse reactions in the prevention and treatment of cerebral ischemia. The research on the effect of TCM in improving cerebral ischemia injury by regulating the structure and metabolism of intestinal flora and maintaining the function of intestinal flora has gradually become a hot topic. Based on the interaction between TCM and intestinal flora in relevant literature in recent years， this review investigated the mechanism of anti-cerebral ischemic injury of TCM via regulating intestinal flora structure， affecting intestinal flora metabolism， and regulating body immunity and made a summary， proving a basis for further elucidating the role of intestinal flora in cerebral ischemia and the mechanism of TCM in prevention and treatment of ischemic stroke.

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

Objective:To construct a scientific and reasonable early warning evaluation index system for high-risk pregnancy during childbirth, so as to provide a content framework for the establishment of an information management platform.Methods:Convenience sampling was used to select 15 experts from 2 colleges and universities, 5 ClassⅢ Grade A general hospitals and 2 ClassⅢ Grade A maternal and child health hospitals in Henan Province as the subject of consultation. The early warning evaluation indicators of high-risk pregnancy during childbirth were determined through literature research, group discussion, and Delphi expert consultation method. Convenience sampling method was adopted to select 288 pregnant women admitted to the hospital for delivery from February to April 2020 in a ClassⅢ Grade A hospital in Henan Province as the research object. The early warning evaluation index system for high-risk pregnancy during childbirth was used to evaluate pregnant women.Results:The final early warning evaluation index system for high-risk pregnancy during childbirth included 7 first-level indicators and 27 second-level indicators. The expert authority coefficients of the two rounds of consultation were 0.91 and 0.93, respectively, and the Kendall harmony coefficients were 0.241 and 0.385, respectively ( P<0.001) . The area under the ROC curve predicted by the early warning evaluation index system for high-risk pregnancy during childbirth was> 0.85, and the best cut-off point was 9.98. Conclusions:The constructed early warning evaluation index system for high-risk pregnancy during childbirth has comprehensive content and high reliability, which will help midwives to identify high-risk pregnancy during childbirth.

[Objective]To investigate the effect of KIF23 gene expression on the proliferation,migration and invasion of human hepatocellular carcinoma HepG2 cells in vitro,and to explore the possible mechanism.[Methods]The KIF23 siRNA was transfected into HepG2 cells by lipofectamine 3000.The expression of KIF23 mRNA and protein in HepG2 cells was de-tected by qRT-PCR and Western blot.The effect of silencing KIF23 on the proliferation of HepG2 cells was studied by CCK-8 assay and plate clone formation assay.The tumor cell abilities of migration and invasion after transfection were measured by scratch assay and Transwell assay.The expression of protein kinase B(PKB/Akt)and phosphorylated Akt(p-Akt)protein in HepG2 cells transfected with KIF23-siRNA2 was detected by Western blot.[Results]KIF23-siRNA could effectively si-lence the expression of KIF23 mRNA and protein in HepG2 cells(P<0.01).The results of CCK-8 assay,plate clone forma-tion assay,scratch assay and Transwell assay demonstrated that the cell proliferation,migration and invasion ability of the KIF23-siRNA2 interference group were significantly inhibited,compared to the negative control group and the blank control group(P<0.05).The expression level of total Akt protein in HepG2 cells was not changed,but the expression level of phos-phorylated Akt protein was down-regulated(P<0.05).[Conclusions]KIF23 may promote the proliferation,migration and in-vasion of human hepatocellular carcinoma cells by activating Akt signal transduction pathway.KIF23 is expected to be a new target for gene therapy of hepatocellular carcinoma.

Chitinases(EC3.2.1.14), which are present in various organisms, catalyze the hydrolytic cleavage of chitin and play a vital role in plant defense mechanisms against fungal pathogens.In addition, the chitinases are well known to regulate plant growth and development and are involved in programmed cell death(PCD).A chitinase expressed sequence tag(EST) was isolated from Panax notoginseng, and the full-length cDNA of this EST was cloned with the method of rapid amplification of cDNA ends and named as PnCHI1. PnCHI1 was 1 022 bp in length and contained an intact open reading frame(ORF) of 822 bp, a 26 bp 5'-untranslated region(UTR), and a 174 bp 3'-UTR.The predicted protein of PnCHI1 with 273 amino acid residues belongs to glycoside hydrolase family 19 and fell into the class IV of chitinases through phylogenetic analysis.QRT-PCR analysis showed that the expression of PnCHI1 was induced by methyl jasmonate, ethylene, H2O2, and salicylic acid.PnCHI1 was quickly induced after inoculation with Alternaria panax.Moreover, the expression level of PnCHI1 was increased after pretreatment with methyl jasmonate, and then the transcription level of PnCHI1was sharp increased after inoculation with Fusarium solani,and the highest transcription level was achieved at 4 h post inoculation.But the expression level of PnCHI1 in the sterile water pretreated P.notoginseng was increased gradually after inoculation with F.solani, and the highest expression level was achieved at 48 h post inoculation.All the results of present study indicated that PnCHI1 was involved in defense response of P.notoginseng against the F.solani and A.panax.

Gastric cancer is one of the most common malignancies worldwide; however, the molecular mechanism in tumorigenesis still needs exploration. BCL2L11 belongs to the BCL-2 family, and acts as a central regulator of the intrinsic apoptotic cascade and mediates cell apoptosis. Although miRNAs have been reported to be involved in each stage of cancer development, the role of miR-24 in GC has not been reported yet. In the present study, miR-24 was found to be up-regulated while the expression of BCL2L11 was inhibited in tumor tissues of GC. Studies from both in vitro and in vivo shown that miR-24 regulates BCL2L11 expression by directly binding with 3'UTR of mRNA, thus promoting cell growth, migration while inhibiting cell apoptosis. Therefore, miR-24 is a novel onco-miRNA that can be potential drug targets for future clinical use.
Animals ; Apoptosis ; genetics ; Apoptosis Regulatory Proteins ; deficiency ; genetics ; Base Sequence ; Bcl-2-Like Protein 11 ; Cell Line, Tumor ; Cell Movement ; genetics ; Cell Proliferation ; genetics ; Down-Regulation ; genetics ; Gene Silencing ; Male ; Membrane Proteins ; deficiency ; genetics ; Mice ; MicroRNAs ; genetics ; Proto-Oncogene Proteins ; deficiency ; genetics ; Rats ; Stomach Neoplasms ; genetics ; pathology

Animals ; Cellular Reprogramming ; Dentate Gyrus ; cytology ; Fibroblasts ; cytology ; Mice ; Neural Stem Cells ; cytology ; transplantation ; Swine

Hannum and colleagues performed DNA methylation sequencing to examine the relationship between DNA methylome and aging rate. Notably, they succeeded in building a quantitative and reproducible model based on the epigenetic bio-markers to predict aging rate with high accuracy. This progress enlightens us in many aspects particularly in applying this novel set of bio-markers on studying the mechanism of aging rate using adult tissue-specific stem cells, building up a potential quantitative model to explore the mechanism for other epigenetic factors like non-coding RNA, and understanding the principle and mechanism of 3D chromatin structure in epigenetic modulation.
Aging ; genetics ; pathology ; Base Sequence ; Chromatin ; genetics ; DNA Methylation ; genetics ; Epigenesis, Genetic ; Genome, Human ; Humans ; RNA, Untranslated ; genetics ; Sequence Analysis, DNA ; trends

Objective To compare the efficacy and safety of domestic levosimendan versus dobutamine for patients with acute decompensated heart failure (ADHF).Methods ADHF patients from 8 medical centers were recruited in this multicenter,blind,positive-controlled,randomized study and received 24 h intravenous levosimendan (n =114) or dobutamine (n =114) therapy.SWAN-GANZ catheter was performed in patients with pulmonary capillary wedge pressure (PCWP) ≥ 15 mm Hg ( 1 mm Hg =0.133kPa) and cardiac index (CI) ≤ 2.5 L · min-1 · m-2 ( n =39 each).Results Compared with baseline level,LVEFincreased [(31.56 ±9.69)％ vs.(28.44 ±7.08)％,P＜0.01] at 24 h in both groups.LVEF increase at 24 h was similar between two groups [ ( 3.11 ± 6.90 ) ％ vs.( 3.00 ± 6.63 ) ％,P ＞0.05].The PCWP decrease at 24 h was significantly greater in levosimendan group than in dobutamine group [ ( - 8.90 ± 7.14) mm Hg vs.( - 5.64 ± 6.83) mm Hg,P =0.04 ].Decrease in NT-proBNP at 3 days was also more significant in levosimendan group than in dobutamine group [ the percentage change compared to baseline:( - 22.36 ± 38.98) ％ vs.( - 8.56 ± 42.42) ％,P ＜ 0.01 ].Dyspnea improvement at 24 h was more significant in levosimendan group than in dobutamine group.The incidences of adverse reactions and events were similar between two groups.Conclusion LVEF improvement is similar between dobutamine and domestic levosimendan while greater decreases in PCWP and NT-proBNP are achieved with domestic levosimendan in patients with ADHF.