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

Background and purpose: Cervical conization is a common operation to treat precancerous tissues performed under non-intubated anesthesia. As common opioid analgesics have side effects of inhibiting respiration and circulation, other kinds of analgesic drugs should be coordinated to improve the anesthetic effect, without interfering the respiration and circulation. This study aimed to evaluate the effects of dezocine or flurbiprofen combined with propofolremifentanil in cervical precancerosis conization. Methods: Sixty patients who underwent cervical conization were equally randomized into dezocine group (group D), flurbiprofen group (group F) and 0.9％ natural saline (group N) with 20 patients in each group, and received dezocine 0.1 mg/kg, flurbiprofen 1 mg/kg or 0.9％ natural saline in 5 mL respectively before anesthesia induction. During the anesthesia induction, the targeted control infusion of remifentanil in effect concentration was set at 1.5 ng/mL, and the plasma concentration of propofol was set at 2 μg/mL. Heart rate (HR), respiratory rate (RR), surplus pulse O2 (SPO2) and mean arterial pressure (MAP), MAP were monitored before the anesthesia induction (T0) and after (T1), at the start of cervical conization (T2), and at the end of operation (T3). The incidence of respiratory depression and body movements during surgery were observed. The satisfaction degree of the surgeon to the opening status of cervix was evaluated. The post-operative recovery time, visual analogue scale (VAS) scores, nausea and vomiting in the following 12 hours were also recorded. Results: The HR, RR, SPO2 and MAP in three groups did not have any significant change (P＞0.05) at T0, T1 and T3. At T2 the HR and MAP decreased significantly in group D and group F compared with group N (P＜0.05), and there was no significant difference between group D and group F (P＞0.05). The surgical satisfaction degree of "Good" in group D was 80％, significantly higher than that in group N (30％) and group F (50％), indicating a better cervix opening in group D. The recovery time in three groups had no significant difference, and the VAS scores in group D and group F were lower than those in group N (P＜0.05) after operation, and patients did not have nausea or vomiting in the following 12 hours. Conclusion: Both the dezocine and flurbiprofen could improve the anesthetic effect in cervical conization and post-operative comfort, with less respiratory or circulation depression. Dezocine showed better improvement than flurbiprofen in cervix opening and the inhibition of stress response and body movements during surgery.

Objective To evaluate the minimum inhibitory concentration (MIC) and influence factors of cefathiamidine against clinical isolates from recent years in China.Methods MIC were tested by two fold agar dilution method.The effect of various experimental conditions (such as inoculation quantity,pH value of medium,percentage of serum)on MIC of cefathiamidine was evaluated.Results A total of 794 clinical strains were tested and cefathiamidine had showed excellent antibacterial activity against gram-positive bacterial.The MIC90 of cefathiamidine against methicillin-susceptible S.aureus (MSSA) and S.epidermidis (MSSE)were 0.50,0.12 mg · L-1,respectively.The MIC90 values of cefathiami-dine had against penicillin-susceptible S.pneumoniae (PSSP) and peni-cillin-nonsusceptible S.pneumoniae(PNSSP) were 0.12 mg· L-1 and not more than 1 mg · L-1,respectively.Against S.pyogenes,the MIC90 was 8 μg · L-1.The MIC90 of cefathiamidine against ampicillin-susceptible E.faecalis and E.faecium were 1,16 mg · L-1,respectively.The MIC90 of cefathiamidine against ampicillin-susceptible Haemophilus spp.and Moraxella catarrhalis were not more than 4 mg L-1 Cefathiamidine also had some antibacterial activity against gram-positive anaerobia.The factors including inoculation quantity,pH value of medium and percentage of serum had no effect on MIC values.Conclusion Cefathiamidine exhibited good activity against gram-positive bacterial including Enterococcus spp..

Objective To evaluate in vitro synergy between palmatine and commonly used antibiotic against main clinical isolated strains in recent three years.Methods All of 118 strains isolated in recent three years and 2 standard strains were studied.Minimal inhibition concentrations (MIC) were tested by agar dilution method and combination effects were measured by checkerboard method.Results Palmatine showed moderate in vitro activity against Staphylococcus.Synergy was detected with palmatine in combination with levofloxacin against gram-positive and negative strains,though synergistic rate less than 20％.Synergy was not show between palmatine and linezolid.Additive effect was found widely between palmatine and two agents against almost all tested species.Conclusion The results of in vitro synergy tests may be different sometimes on account of various strains,methods,etc.So,more deeper understanding of action mechanism of traditional Chinese medicine and correlation between in vitro test and clinical outcomes will help medical to select antibiotic more suitablly.

Objective To evaluate the in vivo antibacterial effect of cefathiamidinein against mouse septicemia.Methods Experimental model of mouse septicemia was established by intraperitoneally injection with 0.5 mL minimum lethal dose (MLD) bacteria.The 0.2 mL different concentrations of drugs were injected through caudal vein.Cefathiamidine,cefazolin and ampicillin adopted two methods of dose regimen,which are single-dose and two-dose;while,both ceftriaxone and levofloxacin adopted single-dose.The survival time of the infected mouse was monitored for 1-7 d.The 50％,95％ effective doses(ED50,ED95) were determined by the Bi-level integrated system synthesis (BLISS) method.The antibacterial activities between cefiazine and control drugs were compared.In vivo protection experiments were carned out on 3 standard strains and 7 pathogenic strains isolated through single dose.Results The cefathiamidine had good antibacterial activity in vivo against Streptococcus pneumonia and Enterococcus faecalis.The ED50 of single-dose was between 1.43-1.71 mg · kg-1,which was significantly superior to cefazolin and was similar to levofloxacin.According to the results of two -dose regimen,the ED50 values of cefathiamidine against Sreptococcus pneumonia,Staphylococcus aureus and Haemophilus influenza significantly declined,which were between 0.78-14.78 mg · kg-1.However,with regard to Enterococcus faecalis,the ED50 value of two-dose increased compared to that of single-dose,which could be related to the fact that low plasma concentration affected protective effects in vivo.Conclusion Cefathiamidine had a better antibacteria effect in vivo against gram-positive bacteria,especially Streptococcus pneumonia and Enterococcus faecalis.Through the comparison between single-dose and two-dose,it is more reasonable to adopt two-dose or multiple-dose of cefathiamidine with regard to most strains.

Objective To analyze the related pathogenicity gene mutations in a sudden death of hypertrophic cardiomyopathy (HCM) on whole exome level.Methods Whole exome sequencing (WES) was been performed on a sudden death case sample with pathological features of HCM by Illumina(R) Hiseq 2500 platform.Using hgl9 as the reference sequences,the sequencing data were analyzed.Suspicious single nucleotide variants (SNV) were screened,and the conservatism and function were analyzed by the software such as PhyloP,PolyPhen-2,SIFT,etc.Results After screening,a heterozygous mutation C719R was finally identified in the gene MYBPC3 of this case.Conclusion The molecular anatomy on whole exome level by second generation sequencing technology can help to define the molecular mechanism of HCM and provide a new mothed and thought for analysis of death cause.

Objective To investigate the effects of tetramethylprazine (TMP) on left ventricular hypertrophy and the regulation of nicotinamide-adenine dinucleotide(NADPH) oxidases in renovascular hypertension of rat.Methods Hypertensive rats were obtained by using two-kidney-two-clip (2K2C) method.Rats were classified into sham-operated group,model group,low,high dose experimental groups (TMP,30,60 mg · kg-1 · d-1) and control group (candesartan,10 mg · kg-1 · d-1).The drugs were continuously administered for 2 weeks.Left ventricular (LV) hemodynamic parameters,serum superoxide ismutase (SOD),dmalondialdehyde (MDA) and hydrogen peroxide(H2O2)levels were measured.The ratio of LV weight to body weight (LVW/BW) was calculated.Hematoxylin-eosin(HE) staining was used for morphological analysis.RT-polymerase chain reaction and Western-blot were performed to investigate the protein expressions of brain natriuretic peptide (BNP),β-myosin heavy chain(β-MHC) and NADPH oxidases(Nox2,Nox4 and P47phox).Results Compared with model group,aortic systolic pressure (AoSP),aortic diastolic pressure (AoDP),LV end-systolic pressure (LVESP),LV end-diastolic pressure(LVEDP) significantly decreased in low,high dose experimental groups with siginificanly (all P ＜ 0.05) while (+ dp/dtmax) and (-dp/dtmax) increased in low,high dose experimental groups with siginificanly (P ＜ 0.05).Compared with model group on LVW/BW (2.8 ± 0.3) mg · g-1,LVW/BW of (1.9 ± 0.2),(1.7 ± 0.4) mg · g-1 in low,high dose experimental groups significantly decreased (P ＜ 0.05).Compared with model group SOD significantly increased while MDA and H2O2 decreased in low,high dose experimental groups with significandy (all P ＜ 0.05).The protein expressions of Nox2 in low,high experimental groups and model group were 0.82 ± 0.08,0.57 ± 0.05,0.30 ± 0.13;the protein expressions of Nox4 in above three groups were 1.00±0.10,0.79 ± 0.07,1.32 ± 0.15 and the protein expressions of P47phox in above three groups were 0.88 ± 0.08,0.65 ± 0.06,1.23 ± 0.15,compared with model group,the protein expression significantly decreased in low,high dose experimental groups with significantly (all P ＜ 0.05).Conclusion TMP attenuated cardiac hypertrophy possibly through decreasing NADPH oxidases (Nox2,Nox4,P47phox) expressions and oxidative stress in renovascular hypertensive rats.

Objective To evaluate the optimal administration regimen of flomoxef for the bacterial infection based on pharmacokinetic/pharmacodynamic (PK/PD) models.Methods A literature search was conducted in PubMed to capture the pharmacokinetic data of flomoxef.Minimum inhibitory concentrations (MICs) were determined using two-fold agar dilution method.The percent time that drug concentration exceeds the minimum inhibitory concentration (％fT＞MIC) was used as the PK/PD indicator correlated with efficacy.Monte Carlo simulation was employed to determine the appropriate regimens of flomoxef based on the probability of target attainment (PTA) against the clinical isolates of strains.Results The regimens of 1 g q6 h,1 g q8 h and 1 g q12 h with 1 hour infusion at 70％ of ％ fT＞MIC achieved 93.1％,89.1％ and 66.8％ of PTA against Escherichia coli (ESBL +),respectively.For the Klebsiella pneumoniae (ESBL+),these regimens achieved 81.8％,78.7％ and 62.3％ of PTA at ％fT＞MIC =70％.The regimen of 2 g q12 h achieved the similar PTA as 1g q6 h and 1 g q8 h at 50％ and 70％ of ％fT＞MIC,but not at higher ％ fT＞MIC.Furthermore,flomoxef also showed potent bactericidal activity against Escherichia coli (ESBL-),Klebsiella pneumoniae (ESBL-),methicillin-susceptible S.aureus (MSSA),methicillin-susceptible S.Epidermidis (MSSE) and Moraxella catarrhalis,etc.with all dosing regimens according to the PK/PD analysis.Conclusion As a time-dependent antibiotic,the clinical outcome of flomoxef can be improved by shortening dosing interval,extending infusion time and/or increasing dose.The first two strategies played more significant roles.

Objective To evaluate the pharmacokinetics of multiple dose of antofloxacin hydroehloride tablet under fast and food state in Chinese healthy subjects.Methods A randomized,open and multiple dose study was conducted.Three dose groups with 16 subjects per group were given the dose of 200,400 and 600 mg antofloxacin hydrochloride tablet,once daily for 7 days respectively.8 subjects (4 male and 4 female) were administrated under fast state and 8 subjects (4 male and 4 female) under food state in each dose.The concentrations of antofloxacin in plasma and urine were determined by HPLC method.Results The main pharmacokinetics parameters of three dose (200,400 and 600 mg) under fast at first day were as follows:Cmax were (2.23 ±0.38),(4.59 ± 1.40),(5.03 ±0.77)mg · L-1,t1/2βwere(11.99 ±3.31),(10.97 ±5.33),(14.39 ± 1.63)h,tmax were (1.37 ±0.78),(2.04 ± 1.42),(2.90 ±2.02)h,AUC0-t were (27.61 ±6.14),(51.77 ±22.09),(73.62 ±10.14)mg · L-1 · h,AUC0-∞ were (38.28 ± 13.49),(72.28 ± 42.80),(108.91 ± 13.26) mg · L-1 · h,V/F were (92.84 ± 12.98),(91.90±14.55),(116.28±22.62)L,CL/F were (5.73 ±1.71),(7.67 ±4.65),(5.58 ±0.66)L· h-1,respectively;under food state at first day,Cmax were (2.36 ± 0.43),(4.11 ± 1.53),(5.60 ± 1.00) mg · L-1,t1/2β were (14.37 ±4.34),(11.25 ±5.39),(15.53 ±2.94) h,tmax were (2.69 ± 1.62),(2.40 ± 1.50),(2.65 ±1.29)h,AUC0-t were (33.69 ±4.00),(48.07 ±22.19),(78.01 ±17.18)mg · L-1 · h,AUC0-∞ were (50.71 ± 8.86),(67.37 ± 41.98),(121.31.66 ± 33.54) mg · L-1 · h,V/F were (81.04 ± 16.35),(106.32 ±34.33),(114.08±20.00)L,CL/Fwere (4.07 ±0.82),(8.28 ±5.29),(5.23 ±1.18)L · h-1,respectively.After 7 days,the main pharmacokinetics parameters of three dose (200,400 and 600 mg) under fast were as follows:Cmax were (3.69 ± 1.39),(7.54 ± 2.95),(8.50 ± 0.93) mg · L-1,t1/2β were (25.22 ± 3.34),(19.56 ±12.47),(15.95 ±2.85)h,tmax were (1.64±1.29),(1.31 ±0.79),(1.60±1.07)h;AUC0-twere (72.29 ± 24.00),(142.96 ± 67.20),(180.81 ± 35.33) mg · L-1 · h,AUC0-∞ were (75.90 ± 25.46),(148.26 ±69.86),(183.30±35.11)mg · L-1 · h,V/F were (184.77 ±52.51),(119.22 ±53.92),(118.91 ±30.13) L,CL/F were (5.06 ± 1.18),(4.75 ± 1.72),(5.15 ±0.72)L · h-1;under food state,Cmax were (3.53 ± 1.06),(6.54 ±1.43),(8.52 ±1.80)mg · L-1,t1/2βwere (24.08 ±6.12),(20.64 ±9.16),(18.69 ±6.49)h,tmax were (2.94 ± 1.02),(1.96 ± 1.05),(2.69 ±0.96)h,AUC0-t were (94.71 ±31.03),(142.17 ±52.46),(211.34.01 ±52.99)mg · L-1 · h,AUC0-∞were (99.32 ±33.93),(149.77 ±55.19),(213.76 ±53.00)mg· L-1 · h,V/F were (139.40±37.39),(140.24±71.11),(130.20 ±71.09)L;CL/F were (4.11 ±1.13),(4.81 ± 1.17),(4.69 ± 0.88)L · h-1.Urinary recovery rates after 7 days doses from zero to 120 h were (67.24±13.56)％,(68.62±14.45)％ and (74.31 ±12.99)％,respectively.Conclusion Food had no obvious influence on pharmacokinetics parameters after multiple oral dose of 200,400 and 600 mg antofloxacin hydrochloride tablet under fast and food state,except that tmax increased.There was no accumulation in human body.It can be considered that food had no effect in the clinical use of antofloxacin hydrochloride tablet.