To systematically evaluate the efficacy and safety of acupuncture versus Flunarizine hydrochloride in the treatment of migraine. Four Chinese databases(CNKI, VIP, WanFang, CBM), three English databases(Cochrane Library, EMbase, Medline) and ClinicalTrail.gov were systematically and comprehensively retrieved. The retrieval time was from the establishment of each database to January 8, 2020. Randomized controlled trial(RCT) for acupuncture versus Flunarizine in the treatment of migraine were screened out according to inclusion criteria and exclusion criteria. The included studies were evaluated with the Cochrane bias risk assessment tool. The included studies was conducted by RevMan 5.3, and the outcome indicators were evaluated for evidence quality and strength of recommendation by the GRADE system. A total of 1 033 literatures were retrieved, and 23 studies were finally included. Except for 4 multiarm tests, the total sample size was 1 548, including 785 in acupuncture group and 763 in Flunarizine group. The overall quality of the included studies was not high. Meta-analysis results showed that the acupuncture group was superior to the Flunarizine group in reduction of headache frequency(SMD=-1.00, 95%CI[-1.45,-0.54], P<0.000 1). In reduction of headache intensity, acupuncture group was superior to Flunarizine group(SMD=-1.05, 95%CI[-1.41,-0.68], P<0.000 01). In reduction of headache duration, acupuncture group was superior to Flunarizine group(SMD=-1.42, 95%CI[-1.83,-1.02], P<0.000 1). The acupuncture group was superior to Flunarizine group(MD=-0.17, 95%CI[-0.21,-0.13], P<0.000 01) in reduction of the painkillers taking frequency. The acupuncture group was superior to Flunarizine group(SMD=-0.94, 95%CI[-1.35,-0.52], P<0.000 1) in allevia-tion of paroxysmal symptoms, such as nausea and vomiting. The GRADE system showed that the evidence level of the above indicators was extremely low, and the strength of recommendation was low. As for the occurrence of adverse reactions, the adverse reactions reported in the acupuncture group included in the study were all mild adverse reactions, like drowsiness, subcutaneous bleeding, local pain, subcutaneous hematoma and dizziness needle. The available evidence showed that acupuncture has a better efficacy than Flunarizine hydrochloride in the treatment of migraine in adult patients. However, due to the high bias risk in the included studies, the conclusions of this study shall be adopted with caution, and more high-quality studies shall be carried out for verification in the future.
Acupuncture Therapy ; Flunarizine/therapeutic use* ; Humans ; Migraine Disorders/therapy* ; Treatment Outcome

To evaluate the efficacy and safety of Yangxue Qingnao Granules alone or combined with calcium channel blocker in treatment of migraine. In this study, four Chinese databases(CNKI, VIP, WanFang, CBM), three English databases(Cochrane Library, EMbase, Medline) and clinical trials registration center(ClinicalTrials.gov) were retrieved. The retrieval time was from the establishment of each database to January 8, 2020. According to the set inclusion criteria and exclusion criteria,the randomized controlled trial(RCT) of Yangxue Qingnao Granules alone or combined with calcium channel blocker was selected. The "Cochrane bias risk assessment" tool was used to evaluate the quality of the included studies. RevMan 5.3 was used to conduct Meta-analysis of the included studies and grade system was used to evaluate the evidence quality of the outcome indicators. A total of 583 documents were retrieved and finally included in 23 studies, with a total sample size of 2 308 cases, 1 171 cases in the treatment group and 1 137 cases in the control group. The overall quality of the research included was not high. Meta-analysis showed that,(1)in terms of effective rate, Yangxue Qingnao Granules combined with calcium channel blocker was better than calcium channel blocker(RR=1.24, 95%CI[1.17, 1.32], P<0.000 01), and there was no significant difference between Yangxue Qingnao Granules and calcium channel blocker(RR=1.36, 95%CI[0.91, 2.03], P=0.14).(2)In terms of reducing headache frequency, when the unit of headache frequency was times per month, Yangxue Qingnao Granules combined with calcium channel blocker was better than calcium channel blocker(MD=-1.39, 95%CI[-1.83,-0.95], P<0.000 01), when the unit of headache frequency was times daily, Yangxue Qingnao Granules combined with calcium channel blocker was better than calcium channel blocker(MD=-2.08, 95%CI[-2.34,-1.82], P<0.000 01).(3)In terms of headache intensity, when headache intensity was scored by pain intensity, Yangxue Qingnao Granules combined with calcium channel blocker was better than calcium channel blocker(MD=-0.70, 95%CI[-0.81,-0.59], P<0.000 01), when headache intensity was scored by VAS score, Yangxue Qingnao Granules combined with calcium channel blocker was better than calcium channel blocker(MD=-1.59, 95%CI[-2.13,-1.06], P<0.000 01).(4)In terms of reducing headache duration, Yangxue Qingnao Granules combined with calcium channel blocker was better than calcium channel blocker(SMD=-3.13, 95%CI[-4.12,-2.15], P<0.000 01). GRADE system showed that the evidence level of the above outcome indicators was low and extremely low. Twelve cases of adverse reactions were reported, all of which were mild. The results showed that the combination of Yang-xue Qingnao Granules can improve the effective rate, reduce the headache frequency, the headache intensity and the headache duration, and had good safety and low incidence of adverse reactions compared with the single calcium channel blocker. However, there was no difference in the effective rate between Yangxue Qingnao Granules alone and calcium channel blocker. In view of the low quality of this study, which affects the reliability of the conclusion, it is necessary to use the conclusion of this study carefully, and more high-quality randomized controlled trials are needed to further verify in the future.
Drugs, Chinese Herbal/adverse effects* ; Humans ; Migraine Disorders/drug therapy* ; Reproducibility of Results

The aim of this paper was to investigate the mechanism of the active peptide DP17 of Eupolyphaga steleophaga in the treatment of hyperlipidemia rats. HPLC and MADIL-TOF/TOF-MS were used for the amino acid sequence analysis and solid-phase synthesis on the active peptide of E. steleophaga which were obtained by biomimetic enzymatic hydrolysis, separation and purification. The hyperlipidemia model was established by feeding with high-fat diet.Twenty days later, the rats in the blank group and the model group were given the saline and the rats in remaining groups were given the corresponding drugs by oral administration. After administration for 4 weeks, the levels of triglyceride(TG), total cholesterol(TC) and low density lipoprotein(LDL) in serum, the levels of TG, TC, adenosine monophosphate(AMP), adenosine triphosphate(ATP) in liver tissues and TG in feces were detected, respectively. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of liver tissues. The Real-time fluorescence quantitative PCR method was used to detect the expression of acetyl coa carboxylase(ACC) and hydroxymethylglutaryl-coa reductase(HMGCR) mRNA in liver tissues. The expression of mammalian target of rapamycin(mTORC1) protein and adenosine 5'-monophosphate-activated protein kinase(AMPK) in liver tissues were detected by Western blot. The analysis showed that the amino acid sequence of active peptide from E. steleophaga was DAVPGAGPAGCHPGAGP(DP17). The results of pharmacological experiments showed that after oral administration of DP17 in rats, the levels of TG, TC and LDL in serum as well as TG and TC levels in liver tissues were significantly decreased(P<0.05), while the levels of AMP, ATP in liver tissues and TG content in feces were significantly increased(P<0.05); the liver steatosis of rats was significantly relieved; the expression of ACC, HMGCR mRNA and mTORC1 protein in liver tissues were significantly reduced, while the expression of AMPK phosphorylated protein was significantly increased(P<0.05). DP17, the active peptide of E. steleophag can significantly reduce lipid accumulation in liver tissues, and it may play a role in reducing blood lipids by regulating the energy metabolism balance in the body and activating AMPK/mTOR signaling pathway.
Animals ; Diet, High-Fat/adverse effects* ; Hyperlipidemias/genetics* ; Lipids ; Liver ; Peptides ; Rats ; Triglycerides

OBJECTIVE: Abnormalities of liver-related indices are common in ICU patients, but the effects of cholestasis and hypoxic hepatitis in critically ill patients remains unclarified. The purpose of this study was to investigate the effects of cholestasis and hypoxic liver dysfunction on the prognosis of ICU patients. METHODS: A retrospective study was conducted based on the data of patients admitted to the ICU for the first time between 2001 and 2011 archived in the MIMIC-Ⅲ database. The patients were divided into cholestasis, hypoxic hepatitis and control groups, and their 28-day case fatality rate as the primary outcome was compared among the groups. RESULTS: A total of 5852 ICU patients were included in the analysis. The incidence of cholestasis and hypoxic liver dysfunction was 31.9% (1869/5852) and 17.9% (1046/5852), respectively. There was no significant difference in 28-day case fatality rate between cholestasis group and the control group. Compared with the control group, the patients with hypoxic hepatitis had a significantly higher 28-day case fatality rate (46% 35%, < 0.01), a higher hospital case fatality rate (40% 31%, < 0.01), and a higher ICU case fatality rate (35.7% 22.2%, < 0.01). Logistic regression analysis showed that lactic acid (LAC), aspartate transaminase (AST), and international standard ratio (INR) were independent risk factors for 28-day case fatality rate. CONCLUSIONS The incidence of cholestatic liver dysfunction is higher than that of hypoxic hepatitis, but it does not increase the 28-day case fatality rate of the ICU patients, suggesting that cholestatic liver dysfunction may be the early adaptation of the liver to critical diseases.
Cholestasis ; Hepatitis ; Humans ; Intensive Care Units ; Prognosis ; Retrospective Studies

Objective Acute lung injury induced by variety causes can be reduced by mesenchymal stem cells.Some studies have shown that mesenchymal stem cell-derived exosomes have similar features with mesenchymal stem cell,but its role in acute lung injury is less studied.The study was to investigate the protective role and underlying mechanisms of bone marrow mesenchymal stem cell-derived exosomes (BMSC-DEs) on smoke inhalation injury (SⅡ) in rats.Methods Thirty Wistar rats were randomly divided into 3 equal groups:normal control group,smoke inhalation injury (SⅡ) model group and bone marrow mesenchymal stem cell-derived exosomes (BMSC-DEs) treated group.12 h after establishing the SⅡ model,BMSC-DEs treated group was injected with 0.5 mL BMSC-DEs (derived from 4× 106 BMSCs),and normal control group and SⅡ model group were injected with equivalent volume of normal saline.7 days later,samples were collected.The histopathologic changes of lung were observed after HE staining;BCA was used to test the amounts of total protein in bronchoalveolar lavage fluid (BALF);Enzyme linked immunosorbent assay was used to test the levels of tumor necrosis factor-α (TNF-α) and keratinocyte growth factor (KGF) in the lung tissue;Immunohistochemical was used to test the levels of pulmonary surfactant protein C(SP-C).Results The BALF levels of total protein of SⅡ group was significantly higher than those of normal control group (P＜0.01) and BMSC-DEs groups(P＜0.05);Compared with normal group [(0.164±0.021) ng/L],the levels of tumor necrosis factor-α of SII and BMSC-DEs groups [(0.355±0.106)、(0.234±0.024) ng/L] (P＜ 0.05) were significantly higher,and SⅡ group was higher than that of BMSC-DEs group(P＜0.01);Compared with normal group,the KGF protein expression level in lung tissue of SⅡ group was significantly lower (P＜0.05),but BMSC-DEs group was higher (P＜0.05).BMSC-DEs group was higher than SⅡ group (P＜0.01);Immunohistochemistry showed that the SP-C expression level in lung tissue of SⅡ group was significantly lower than those of other groups (P＜0.05).There was no statistically difference between BMSC-DEs group and control group (P＞0.05).Conclusion BMSC-DEs has a protective effect of smoke inhalation injury rats,the underlying mechanism may be related to BMSC-DEs to reduce inflammation and promote restoration of the alveolar epithelial type Ⅱ.

Objective To systematically evaluate the association between frailty and risk of postoperative delirium.Methods Systematic review of literature was conducted using eight electronic databases:PubMed,Embase,CENTRAL,Web of Science,CNKI,CBM,VIP and Wanfang Data,and prospective cohort studies about association between frailty and postoperative delirium published before March 2017 were included.Two authors independently screened the literature,extracted the data,and assessed the quality using NOS Scale,and meta-analysis was conducted by RevMan 5.3 software.Results A total of eight studies involving 846 patients were included in this review.Meta-analysis showed that:frailty was associated with higher risk of postoperative delirium [OR=3.63,95％CI (2.06,6.40),P＜0.001].Subgroup analysis showed that:①Frailty assessment tool:Fried frailty criteria and other frailty assessment were associated with increased risk of postoperative delirium[OR=5.81,95％CI(3.54,9.77),P＜0.001],[OR=1.76,95％CI(1.06,2.92),P=0.03].②Age:frailty patients aged 60～74 had increased risk of postoperative delirium [OR=5.05,95％CI (3.14,8.12),P＜0.001],but for patients aged ≥ 75,frailty wasn't associated with postoperative delirium [0R=1.73,95％CI (0.99,3.00),P=0.05].③Type of surgery:for cardiovascular and non-cardiovascular surgery patients,frailty was associated with increased risk of postoperative delirium [OR=3.40,95％CI (1.64,7.05),P＜0.001],[OR=4.95,95％CI (2.41,10.16),P＜0.001].Conclusion Frailty can increase the risk of postoperative delirium.In consideration of quantity and quality of included studies,the conclusion needs to be validated by multi-centered prospective cohort studies with large sample size.

Objective To observe the clinical efficacy and safety of ilaprazole enteric-coated tablets combined with clarithromycin tablets and furazolidone tablets in the treatment of elderly peptic ulcer.Methods Ninety-six elderly patients with peptic ulcer were randomly divided into control and treatment groups with 48 cases per group.Control group was treated with omeprazole enteric-coated capsules 40 mg per time,bid,orally + clarithromycin tablets 0.5 g per time,bid,orally + furazolidone tablets 100 mg per time,qd,orally,continuous treatment for 10 days.Treatment group was treated with ilaprazole enteric-coated tablets 5 mg per time,bid,orally + clarithromycin tablets 0.5 g per time,bid,orally,continuous treatment for 5 days,then treated with ilaprazole enteric-coated tablets 5 mg per time,bid,orally + furazolidone tablet 100 mg per time,qd,orally,continuous treatment for 5 days.The clinical efficacy,Helicobacter Pylori (Hp) positive rate,serum vascular endothelial cell growth factor (VEGF),basic fibtroblast growth factor (bFGF),nitric oxide (NO) and adverse drug reactions were compared between two groups.Results After treatment,the total effective rates of treatment and control groups were 95.83％ (46 cases/48 cases) and 72.92％ (35 cases/48 cases) with significant difference (P ＜0.05).After treatment,the main indexes in treatment and control groups were compared:the Hp positive rates were 4.17％ (2 cases/48 cases) and 20.83％ (10 cases/48 cases),the VEGF were(167.28 ± 12.94) and (145.26 ± 17.87) pg · mL-1,the bFGF were (144.38 ± 14.80) and (123.29 ± 14.46) pg · mL-1,the NO were (31.81 ± 3.50) and (40.92 ± 6.32) μmol · L-1,the differences were statistically significant (all P ＜ 0.05).The adverse drug reactions in the treatment group were dizziness,vomiting and constipation,which in control group were dizziness,rash and diarrhea.The total incidences of adverse drug reactions in treatment and control groups were 8.33％ and 16.67％ without significant difference (P ＞ 0.05).Conclusion Ilaprazole enteric-coated tablets combined with clarithromycin tablets and furazolidone tablets have a definitive clinical efficacy in the treatment of elderly peptic ulcer,which can regulate the levels of serum VEGF,bFGF and NO,without increasing the incidence of adverse drug reactions.

Intestine,the body's largest digestive and immune organ,always affects the occurrence and development of cardiovascular disease process.Especially the trimethylamine N-oxide as one of the metabolic derivatives produced by intestinal microbiota,can increase the risk of atherosclerosis and promote cardiovascular diseases such as chronic heart failure.Therefore,changing the level of trimethylamine N-oxide in the circulation by taking different measures to intervene the structure,composition and metabolic activity of intestinal flora can affect the occurrence and development of the disease.Thus,the intestinal flora is recognized as a new target for the treatment of cardiovascular diseases.

Objective To analysis the effect of misopmstol,oxytocin nasal spray and carboprost methylate suppositorites on estrogen,nitric oxide (NO),nitric oxide synthase (NOS) and clinical efficacy in patients with general term vaginal delivery.Methods A total of 600 patients with postpartum hemorrhage were randomly divided into group A,group B and group C,200 cases in each group.Group A was given oxytocin nasal spray,per nostril 0.1 mL,twice a day,group B was given misoprostol,200 μg sublingual,group C received carboprost methylate suppositorites 1 mg,anus.After treatment,the serum levels of estradiol (E2),nitric oxide (NO) and nitric oxide synthase (NOS),bleeding volume,clinical efficacy,adverse drug reactions were compared in three groups.Results After treatment,the total effective rates in group A,B and C were 76.50％ (153/200 cases),86.00％ (172/200 cases),90.50％ (181/200 cases),total effective rate of group C significantly higher than group A (P ＜ 0.05).After treatment,estradiol levels of group A,B,C were (14.75 ±2.09),(17.63 ±2.15),(21.82 ±3.09) nmol · L-1.Levels of NO in group A,B,C were (107.83 ± 11.21),(92.42 ± 10.17),(79.25 ±9.89) nmol · L-1.Levels of NOS in group A,B,C were (25.64 ±3.11),(22.56±3.05),(19.63 ±2.28) nmol · L-1(P ＜0.05).And 2 h bleeding volume were (712.43 ± 40.85),(632.43 ± 42.77),(580.74 ± 37.64) mL in group A,B,C;2-24 h bleeding volume were (138.92 ± 17.86),(126.94 ± 12.93),(103.85 ± 11.13) mL in group A,B,C(P ＜0.05).The adverse drug reactions in group A were nasal irritation,nasal bleeding,incidence of adverse drug reactions was 1.50％ (3/200 cases).The adverse drug reactions in group B were mild nausea,vomiting,dizziness,incidence of adverse drug reactions was 2.50％ (5/200 cases).The adverse drug reactions in group C were diarrhea,nausea and vomiting,incidence of adverse drug reactions was 2.00％ (4/200 cases),with no statistical differences (P ＞ 0.05).Conclusions Compared with the treatment of misoprostol and oxytocin nasal spray,the carboprost methylate suppositorites can significantly improve the serum E2 level,reduce serum NO and NOS levels in patients with postpartum hemorrhage and reduce bleeding.

Objective To investigate the effect of cytochrome P450 2C19 (CYP2C19) gene polymorphism on the antiplatelet therapy of clopidogrel in patients who underwent percutaneous coronary intervention (PCI).Methods Fifty-five patients who underwent PCI,as well as twenty-three healthy subjects,were enrolled in this study.The genotypes of the samples were identified by gene chips hybridization.The contents of soluble P-selectin (CD62p) and platelet glycoprotein GP Ⅱ b/Ⅲ a fibrinogen receptor(PAC-1) in patients who underwent PCI were detected by flow cytometry (FCM).The expressions of platelet activation markers were calculated according to interquartile range method.Results Seven patients with CYP2C19 * 2/* 2 genotypes were poor metabolizers,while twenty-eight patients with CYP2C19 * 1/* 2,CYP2C19 * 1/ * 3 were intermediate metabolizers,twenty patients with CYP2C19 * 1/ * 1 were extensive metabolizers.In intermediate metabolism (* 1/* 2),intermediate metabolism (* 1/* 3) and poor metabolism group,the CD62p expressions were (6.73 ± 5.69) ％,(10.94 ± 9.80) ％,(14.35 ± 6.24) ％,(16.80 ± 13.65) ％,respectively,statistically significant differences were found when compared with the control group;The PAC-1 expressions were (1.06 ± 0.69) ％,(2.10 ± 4.09) ％,(2.37 ± 3.15) ％,(2.89 ± 2.75) ％,and there were significant differences in CD62p and PAC-1 among the groups(P ＜0.05).The genotypes of extensive metabolism was high in the response to clopidogrel,while those of intermediate metabolism were moderate and poor metabolism were low.Conclusion Intermediate metabolism genotype patients could be adjusted to the dose of clopidogrel or the use of other antiplatelet drugs,and the poor metabolism genotype patients should be used other antiplatelet drugs.