Efficacy and Safety of Calcitonin Gene-related Peptide Monoclonal Antibodies in the Preventive Treatment of Migraine：A Bayesian Network Meta-analysis / 中国药房

OBJECTIVE：To systematically evaluate th e efficacy and safety of 4 kinds of calcitonin gene-related peptide （CGRP）monoclonal antibodies in the preventive treatment of migraine ，and to provide evidence-based reference for the clinical treatment of migraine. METHODS ：Retrieved from the Cochrane Library ，PubMed，Embase，CJFD，VIP and Wanfang database ， RCTs about 4 kinds of CGRP monoclonal antibodies （trial Δ 基金项目 ：四川省科技厅重点研发 （重大科技专项 ）项目 group） versus placebo （control group ） in the preventive （No.2019YFS0180） ＊硕士研究生 。研究方向 ：临床药学 、循证药学 。电话：0830- treatment of migraine were collected. After literature screening 3165787。E-mail：lewxinn@outlook.com and data extraction ， the quality evaluation of included # 通信作者：教授，硕士生导师，硕士。研究方向：临床药学、循证 literature was performed by using the bias risk assessment tool 药学。电话：0830-3165787。E-mail：hyl3160131@163.com provided by the Cochrane system evaluator manual 5.1.0. 中国药房 2020年第31卷第18期 China Pharmacy 2020Vol. 31 No. 18 ·2275· Bayesian network Meta-analysis was performed by using GeMTC 0.14.3 software and Stata 16.0 software. RESULTS ：A total of 19 RCTs involving 11 392 patients were included ，involving 10 interventions，such as Erenumab 70，140 mg/month；Fremanezumab 675 mg/3 months，225 mg/month；Galcanezumab 120，240，300 mg/month；Eptinezumab 100 mg/3 months，300 mg/3 months and placebo. Results of Meta-analysis showed that compared with control group ，4 kinds of CGRP monoclonal antibodies significantly reduced the change of mean monthly migraine days （MMD）（P＜0.05）. Among trial groups ，compared with Galcanezumab 300 mg/month [MD ＝－1.30，95％CI（－2.59，－0.05），P＜0.05] and Eptinezumab 100 mg/3 months [MD ＝－1.18， 95％CI（－2.26，－0.03），P＜0.05]，Fremanezumab 225 mg/month could significantly reduce MMD. Network Meta-analysis ranking showed that Fremanezumab 225 mg/month＞Fremanezumab 675 mg/3 months＞Galcanezumab 120 mg/month＞Erenumab 140 mg/month＞Galcanezumab 240 mg/month＞Eptinezumab 300 mg/3 months＞Erenumab 70 mg/month＞Eptinezumab 100 mg/3 months＞Galcanezumab 300 mg/month＞placebo. Compared with control group ，4 kinds of CGRP monoclonal antibodies were significantly increased of the proportion of patients whose mean monthly migraine days reduction ≥50％ compared with baseline （MMD 50）（P＜0.05）. Among trial groups ，compared with Eptinezumab 100 mg/3 months group ，MMD 50 of Fremanezumab 675 mg/3 months group [OR ＝1.51，95％CI（1.02，2.31），P＜0.05]，Fremanezumab 225 mg/month group [OR ＝1.58，95％CI （1.05，2.44），P＜0.05] were increased significantly. Network Meta-analysis ranking showed that Fremanezumab 225 mg/month＞ Fremanezumab 675 mg/3 months＞Erenumab 140 mg/month＞Galcanezumab 120 mg/month＞Eptinezumab 300 mg/3 months＞ Galcanezumab 240 mg/month＞Erenumab 70 mg/month＞Galcanezumab 300 mg/month＞Eptinezumab 100 mg/3 months＞placebo. In terms of safety ，incidence of total adverse events （AE）of trial groups receiving Fremanezumab 675 mg/3 months [OR ＝1.31， 95％CI（1.05，1.64），P＜0.05]，Galcanezumab 240 mg/month [OR ＝1.39，95％CI（1.09，1.74），P＜0.05] were significantly higher than control group. Among trial groups ，compared with Galcanezumab 240 mg/month group ，AE of Erenumab 70 mg/month group [OR ＝0.67，95％CI（0.50，0.93），P＜0.05]，Erenumab 140 mg/month group [OR ＝0.70，95％CI（0.51，0.98），P＜0.05] were decreased significantly. Compared with Fremanezumab 675 mg/3 months group ，AE of Erenumab 70 mg/month group [OR ＝ 0.72，95％CI（0.52，0.98），P＜0.05] were decreased significantly. Network Meta-analysis ranking showed that Galcanezumab 240 mg/month＞ Fremanezumab 675 mg/3 months＞Galcanezumab 120 mg/month＞Galcanezumab 300 mg/month＞Eptinezumab 300 mg/3 months＞Fremanezumab 225 mg/month＞Eptinezumab 100 mg/3 months＞placebo＞Erenumab 140 mg/month＞Erenumab 70 mg/month. CONCLUSIONS ：Four kinds of CGRP monoclonal antibodies are effective in the preventive treatment of migraine ， among which Fremanezumab 225 mg/month is most likely to have the best efficacy and Erenumab 70 mg/month is most likely to have the highest safety.

Efficacy and Safety of Ubrogepant and Rimegepant in the Treatment of Acute Migraine ：A Meta-analysis / 中国药房

OBJECTIVE：To systemat ically evaluate the efficacy and safety of Ubrogepant and Rimegepant in the treatment of acute migraine ，and to provide evidence-based reference for the clinical treatment. METHODS ：Retrieved from PubMed ，Embase， Cochrane Library ，CNKI，VIP，Wanfang database and Clinicaltrials. gov ，randomized controlled trials （RCTs） about the Ubrogepant and Rimegepant （trial group ）versus placebo （control group ）in the treatment of acute migraine were collected during the inception to Jan. 2020. After literature screening and data extraction ，quality assessment was performed using the bias risk assessment tool provided by the Cochrane system evaluator manual 5.1.0. Meta-analysis was performed by using Stata 16.0 software. RESULTS ：Eight RCTs with a total of 7 989 patients were included. The results of Meta-analysis showed that the proportion of patients who were free from pain at 2 h postdose in Ubrogepant group [RR ＝1.65，95％CI（1.38，1.98），P＜0.001] and Rimegepant group [RR ＝1.69，95％CI（1.46，1.95），P＜0.001]，the proportion of patients who were free from the most bothersome symptom at 2 h postdose in Ubrogepant group [RR ＝1.35，95％ CI（1.20，1.53），P＜0.001] and Rimegepant group [RR ＝1.37，95％CI（1.24，1.51），P＜0.001]，and other secondary outcome indicators （ i.e. the proportion of patients with pain relief at 2 h postdose ，the proportion of patients with sustained freedom from pain from 2-24 h postdose ，the proportion of patients with sustained pain relief from 2-24 h postdose ，the proportion of patients without photophobia at 2 h postdose ，the proportion of patients without phonophobia at 2 h postdose ，the proportion of patients without nausea at 2 h postdose ）were all significantly better than control group （P＜0.05）. In terms of safety ，there was no statistical significance in the incidence of total ADR between Ubrogepant group and control group [RR ＝1.04，95％CI（0.87，1.25），P＝0.646]，but the incidence of total ADR in Rimegepant group were significantly higher than control group [RR ＝1.23，95％ CI（1.01，1.50），P＝0.043]. There was no statistical significance in other security indicators （i.e. incidence of nausea ，dizziness，dry mouth ，somnolence，urinary tract infection）in 2 groups（P＞0.05）. CONCLUSIONS ：Ubrogepant and Rimegepant are effective in the treatment of acute migraine. Ubrogepant is safe ，while Rimegepant may increase the incidence of ADR.

Efficacy and Safety of Guselkumab in the Treatment of Moderate-to-severe Plaque Psoriasis ：A Systematic Re- view / 中国药房

OBJECTIVE：To systematically evaluate the efficacy and safety of guselkumab in the treatment of moderate-to- severe plaque psoriasis ，and to provide evidence-based reference for the clinical treatment. METHODS ：Retrieved from PubMed ， Embase，Cochrane Library ，CNKI，VIP，Wanfang database during inception to Oct. 2019，randomized controlled trials （RCTs） about guselkumab versus placebo/positive control in the treatment of moderate-to-severe plaque psoriasis were collected. After literature screening and data extraction ，quality evaluation was performed by using the bias risk evaluation tool recommended by the Cochrane System evaluator manual 5.1.0. Meta-analysis was performed by using Stata 16.0 software. RESULTS ：Eight RCTs with a total of 3 488 patients were included. The results of Meta-analysis indicated that the proportion of patients who achieved 90％ reduction or more from baseline of psoriasis area and severity index （PASI）in guselkumab group was significantly higher than that placebo group [RR ＝26.72，95％CI（15.98，44.70），P＜0.001]，adaliumumab group [RR ＝1.45，95％CI（1.32，1.59）， P＜0.001] and secukinumab group （P＜0.000 1）. The proportion of patients with Investigator ’s Global Assessment （IGA）score of 0 or 1 in guselkumab group was significantly better than placebo group [RR ＝11.15，95％ CI（8.22，15.14），P＜0.001] and adaliumumab group [RR ＝1.27，95％CI（1.19，1.35），P＜0.001]. The proportion of patients with IGA score of 0，the proportion of patients who achieved 75％ reduction or more from baseline of PASI ，dermatology life qu ality index score of 0 or 1 in guselkumab group were signifi cantly superior than placebo group and adaliumumab gr oup，the proportion of patients who achieved 100％ reduction from baseline of PASI in guselkumab group Lewx- was significantly superior than placebo group （P＜0.05）， inn@outlook.com there was no significant difference compared with adaliumumab group （P＞0.05）. There was no statistical significance in the proportion of patients with IGA score of and other secondary outcome indicators between guselkumab and secukinumab group （P＞0.05）. In the safety indicators as total incidence rate of ADR ，rate of withdrawl due to ADR ，etc. ，there was no statistical significance between guselkumab and placebo/ adalimumab groups （P＞0.05）. CONCLUSIONS ：Guselkumab is superior to placebo ，adaliumumab and secukinumab in improving the symptoms of moderate-to-severe plaque psoriasis with good safety .

Efficacy and Safety of Peficitinib for Treating Rheumatoid Arthritis ：A Systematic Review / 中国药房

OBJECTIVE：To systematically evaluate the efficacy and safety of pe ficitinib for treating rheumatoid arthritis （RA），and to provide evidence-based reference for the clinical treatment of RA. METHODS ：Retrieved from PubMed ，Embase， The Cochrane Library ，CJFD，VIP and Wanfang database during from their establishment to September 2019，randomized controlled trials （RCTs）about the efficacy and safety of Peficitinib （trial group ）versus placebo （control group ）in the treatment of RA were collected. The risk of bias assessment tool provided in Cochrane System Evaluator Manual 5.1.0 was used to evaluate the quality after data extracted from clinical studies which met the inclusion criteria. Meta-analysis of the efficacy [the proportion of patients who met the American College of Rheumatology 20％ improvement criteria （ACR20），ACR50，ACR70，the proportion of the patients with 28 joint disease activity index ＜2.6 calculated by erythrocyte sedimentation rate （DAS28-ESR＜2.6），the proportion of patients with 28 joint disease activity index ＜2.6 calculated by C-reactive protein （DAS28-CRP＜2.6），etc.] and safety（incidence of total ADR ）was performed by using Stata 16 statistical software. RESULTS ：Totally 5 RCTs were included ， 药学。E-mail：hyl3160131@163.com 5.11），P＜0.001]，150 mg[RR＝3.52，95％CI（1.78，6.96），P＜ 0.001]}，ACR70{total [RR ＝2.51，95％CI（1.52，4.14），P＜0.001]，100 mg[RR＝3.50，95％CI（1.62，7.58），P＝0.001]，150 mg [RR＝4.59，95％CI（1.47，14.30），P＝0.009]}，DAS28-ESR＜2.6{total [RR ＝4.83，95％CI（3.20，7.28），P＜0.001]，100 mg[RR＝ 5.37，95％CI（2.68，10.77），P＜0.001]，150 mg[RR＝7.44，95％CI（3.78，14.65），P＜0.001]} and DAS 28-CRP＜2.6{total [RR ＝3.41， 95％CI（2.65，4.39），P＜0.001]，100 mg[RR＝4.00，95％CI（2.67，5.99），P＜0.001]，150 mg[RR＝4.45，95％CI（2.99，6.63），P＜ 0.001]} in trial group were significantly higher than control group ，with statistical significance. In term of safety ，there was no statistical significance in the incidence of total ADR [RR ＝1.05，95％ CI（0.94，1.16），P＝0.395] between 2 groups. CONCLUSIONS：For the treatment of RA ，100 mg or 150 mg peficitinib once per day is superior to placebo in terms of ACR 20， ACR50 and ACR 70，DAS28-ESR＜2.6，DAS28-CRP＜2.6； the adverse events are mild and tolerable and it may be a new treatment option for RA.

Efficacy and Safety of Selective Janus Kinace 1 Inhibitor Upadacitinib and Filgotinib in the Treatment of Rheumatoid Arthritis ： A Meta-analysis / 中国药房

OBJECTIVE： To evaluate the therapeutic efficacy and safety of 2 kinds of selective Janus kinase 1 （JAK-1） inhibitor Upadacitinib and Filgotinibfor in the treatment of rheumatoid arthritis， and to provide evidence-based reference for clinical treatment. METHODS： Retrieved from PubMed， Medline， Embase， the Cochrane library， CBM， CJFD， Wanfang database and VIP， RCTs about placebo （control group） versus Upadacitinib or Filgotinibfor （trial group） in the treatment of rheumatoid arthritis on the basis of methotrexate or other antirheumatic drugs were collected during the establishment of the database to Jan. 2019. Meta-analysis of therapeutic efficacy [the proportion of patients with remission rate of 20％ （ACR20）， ACR50， ACR70 according to the criteria of American Rheumatism Association， the proportion of patients with 28-joint disease activity score （DAS28）＜3.2] and safety [the incidence of adverse event （AE）， severe adverse event （SAE）， infection， severe infection， herpes zoster， liver injury] were conducted by using Rev Man 5.3 software after data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0. RESULTS： A total of 8 RCTs were included， involving 2 738 patients. Meta-analysis showed that the proportion of patients with ACR20 [OR＝3.37，95％CI（2.80，4.05），P＜0.001]， ACR50 [OR＝3.78，95％CI（2.98，4.78），P＜0.001] and ACR70 [OR＝4.31，95％CI（3.05，6.09），P＜0.001]， the proportion of patients with DAS28＜3.2 [OR＝3.86，95％CI（2.98，5.00），P＜0.001]， the incidence of AE [OR＝1.33，95％CI（1.11，1.61）， P＝0.002]， the incidence of infection [OR＝1.43，95％CI（1.12，1.81），P＝0.004] in trial group were significantly higher than control group； there was no statistical significance in other indexes （P＞0.05）. CONCLUSIONS： JAK-1 inhibitors Upadacitinib and Filgotinib can improve the effect indexes of ACR20， ACR50 and ACR70 and the proportion of patients with DAS28＜3.2 of rheumatoid arthritis patients； it can not increase the incidence of SAE， severe infection， herpes zoster， liver injury， but can increase the risk of AE and infection.

Establishment of transgenic mice model with overexpression of neuritin in bone marrow / 实用医学杂志

Objective To establish transgenic mice model with over expression of neuritin in bone mar-row,for the further study on the function of neuritin protein in the treatment of peripheral neuropathy. Methods Two pairs of transgenic mice(loxp-stop-loxp-neuritin and lyz-Cre/+)were fed and propagated,the DNA from the mice tails extracted and the genotype of transgenic mice identified by PCR. The wild type mice with B6 were as-signed as the controls,and the immunofluorescence was used to detect the accuracy of the neuritinloxp/+ _lyz -Cre/+. Results The two trensgenetic homozygous mice had the ability to reproduce,and the hybrid offsprings were neuritinloxp/+_lyz-Cre/+,neuritinloxp/-_lyz-Cre/+,neuritinloxp/+_lyz-Cre/-,neuritinloxp/-_lyz-Cre/-. The re-sults were met with the Mendel′s law. The results of immunofluorescence showed that the expression of neuritin of neuritinloxp/+_lyz-Cre/+ mice in bone marrow was significantly higher than the wild type mice(P < 0.05). Con-clusion The PCR method is of high reliability for identification of sub pus genotype and the female neuritinloxp/+mice mating with the male lyz-Cre/+ ones is an effective way for obtaining the neuritinloxp/+_lyz-Cre/+ mice.

The investigation of oxygen nebulizer use in an upper first-class hosipital / 重庆医学

Objective To investigate oxygen nebulizer usage among inpatients in an upper first‐class hospital so that this de‐vice can be used by medical personnel and patients properly .Methods Totally 409 patients were investigated about the usage of the device from May 12th to 30th 2014 ,whose outcomes were analyzed by Excel2007 software .Results The total liquid volume of in‐halation on prescription was much larger than the favorable one ,ranging from 4 to 6 mL .And the Oxygen flow ,ranging from 2 .5 to 3 .5 L/min ,was much lower than the normal flow (ranging from 6 to 8 L/min) .In addition ,all patients failed to breathe normally with occasional deep breaths and failed to gargle timely after corticosteroid inhalation .Only 3% patients cleaned their faces after corticosteroid inhalation ,43 .5% patients sit in an upright position ,44 .0% patients kept the nebulizer vertical during treatment .The accuracy rates of mouthpiece position ,the right time to stop nebulizer therapy ,rinsing the nebulizer with sterile or distilled water and allowing to air dry were 95 .1% ,99 .2% ,and 99 .3% ,respectively .Conclusion There are many common patient use nebulizer incorrectlly in the upper first‐class hospital ,and education and guidance by medical personnel should be strengthened .

Consideration and Suggestion on Clinical Pharmacist Participation in the Treatment of One Dispute Caused by Severe Adverse Drug Reaction / 中国药师

Objective:To discuss the role of clinical pharmacists in avoiding, eliminating and alleviating the effect of medical dis-putes caused by adverse drug reaction ( ADR) and provide reflections and suggestions for the disputes. Methods:Clinical pharmacist participation in the treatment of one case of dispute caused by serious adverse drug reaction was described and analyzed. Results:Clini-cal pharmacists provided opinions and suggestions for the dispute, and promising effect was obtained. Conclusion: Clinical pharma-cists should have excellent medical knowledge and good communication skills, and medical personnel should closely monitor patients in order to avoid medical disputes caused by ADR.

THE INFLUENCE OF UREAPLASMA UREALYTICUM ON SEMEN QUALITY / 中国人兽共患病学报

Aim The seminal plasma of 51 cases of infertile were studied with the PCR technice and ELISA method, of which 20 spectimens (39. 2％ )were Uu positive, 18 spectimens (35. 3 ％ ) were AsAb positive, positive of Uu and AsAb were 11 specimens(21.6％ ). Correlation of seminal plasma that there is significiant between thetwo groups in sperm activity score, sperm viability, liquefy time, deformative rate and sperm morphogenesis. The conclusion is that genital tract infection with Uu can affect semen parameters and diminish semen quality, the fertility ability of human sperm will be destroyed.

Content Determination of Related Substances in Oxaliplatin by HPLC / 中国药房

OBJECTIVE:To establish the HPLC method for the determination of the related substances in oxaliplatin.METHODS:The chromatographic separation was performed on C18,and the mobile phase consisted of methyl alcohol and water(5∶95)with a flow rate of 1.0 mL?min-1.The column temperature was 25 ℃;the detection wavelength was 250 nm and the sample size was 20 ?L.RESULTS:A good linear relationship was obtained for oxaliplatin within the concentration range of 5～17.5 ?g?mL-1(r=0.999 9)with a limit of quantitation of 3 ng(S/N=3).The average content in 3 batches of crude drug vs.their preparations was 0.081% vs.0.15%.CONCLUSION:This method is accurate,reliable and available,and suitable for the content determination of the related substances in oxaliplatin.