Systematic evaluation of the efficacy and safety of intravenous human immunoglobulin combined with cyclophosphamide in the treatment of systemic lupus erythematosus / 中国药房

OBJECTIVE To systematically evaluate the safety and effectiveness of intravenous human immunoglobulin （IVIG） combined with cyclophosphamide in the treatment of systemic lupus erythematosus （SLE）， and to provide an evidence-based basis for clinical medication. METHODS Retrieved from PubMed， Embase， Cochrane Library， CBM， CNKI and Wanfang database， randomized controlled trials （RCTs） about IVIG combined with cyclophosphamide versus cyclophosphamide alone based on glucocorticoids were collected. The quality of the included literature was evaluated with Cochrane 5.1.0 risk of bias assessment tool after literature screening and data extraction， and meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 13 RCTs were included， involving 842 patients. Meta-analysis showed that compared with cyclophosphamide alone， IVIG combined with cyclophosphamide improved the overall response rate of systemic lupus erythematosus [RR＝1.23， 95%CI（1.15， 1.32）， P＜0.000 01]， lowered the systemic lupus erythematosus disease activity index [MD＝－2.05， 95%CI（－2.51， －1.60）， P＜0.000 01]， relieved 24 h proteinuria [MD＝－1.29， 95%CI（－1.57， －1.01）， P＜0.000 01]， reduced the inflammatory factor MCP-4 [MD＝－28.04， 95%CI（－32.72， －23.37， P＜0.000 01）]， IL-4 [MD＝－1.66， 95%CI（－1.96， －1.36）， P＜0.000 01]， and boosted immune complement C3 [SMD＝0.74，95%CI（0.34，1.14）， P＝0.000 3] and complement C4 [SMD＝0.99，95%CI （0.31，1.67）， P＝0.004]； it had similar incidence of adverse drug reactions to cyclophosphamide therapy alone [RR＝0.81， 95%CI （0.57， 1.17）， P＝0.26]. CONCLUSIONS Compared with cyclophosphamide alone， IVIG combined with cyclophosphamide has a positive role in improving the overall response rate of treating SLE， improving clinical symptoms， reducing inflammatory factors， improving immune function， but the results should be interpreted with caution.

Construction of evaluation index system for scientific research ability of hospital pharmacists and analysis of its reliability and validity / 中国药房

OBJECTIVE To construct the evaluation index system for scientific research ability of hospital pharmacists， and provide reference for the improvement of hospital pharmacists’ scientific research ability and the formulation of relevant scientific research policies. METHODS The relevant indexes of scientific research evaluation of hospital pharmacists were extracted by literature analysis， and consultation questionnaire was designed according to Likert grade 5 scoring method. Delphi method was used to conduct two rounds of questionnaire consultation for 28 experts， and the weight of each index was determined by analytic hierarchy process. The reliability and validity of index system were analyzed by questionnaire survey. RESULTS After two rounds of expert correspondence， evaluation index system for scientific research ability of hospital pharmacists was finally determined from three core dimensions： basic scientific research ability， scientific research achievements and transformation ability， academic influence and personnel training （including 11 sub-dimensions and 34 measurement items）. The weight value of each dimension index was determined. The result of reliability and validity analysis confirmed the scientific rationality of the index system. CONCLUSIONS The established evaluation index system for scientific research ability of hospital pharmacists is innovative， comprehensive and scientific. The index system model can provide reference for the improvement of hospital pharmacists’ scientific research ability and the formulation of relevant scientific research policies.

Research hotspots and trends on potentially inappropriate medication from 2012 to 2021 / 中国药房

OBJECTIVE To quantitatively and qualitatively analyze the progress of potentially inappropriate medication （PIM） research by means of bibliometrics， and to predict the hotspots and trends of PIM， so as to provide reference for PIM research in China. METHODS The research literature related to PIM were searched from Web of Science core database， and the publication trend of the literature was analyzed on the bibliometric online analysis platform and CiteSpace 5.8.R3 software. The research results were visualized and analyzed， and the research hotspots of PIM were summarized through gCLUTO. RESULTS About PIM research， the annual number of the literature issued from 2012 to 2021 showed a continuous growth trend totally； the United States had the largest number of literature （241 pieces）； the University of Sydney in Australia was the research institution with the largest number of literature （59 pieces）； O’Mahony D from University College Cork， Ireland， published the most literature （23 pieces）； the research of PIM involved 57 disciplines， among which there was the largest number of literature about gerontology （384 pieces）； International Journal of Clinical Pharmacy was the journal with the largest number of literature （61 pieces）； Journal of the American Geriatrics Society was cited most frequently （1 197 times）. The hotspots of PIM research mainly focused on seven aspects： the standard of PIM， the safety and economy research of PIM， the risk factors research of PIM， the PIM research of chronic patients， the PIM research of antipsychotics， the research of pharmacists’ participation in PIM management， and the PIM research about palliative care of tumor patients. CONCLUSIONS The heat of research on PIM has been on the rise， and there is little cooperation between countries and institutions， and more cooperation is needed. In the future， the focus of Chinese pharmacists’ research on PIM may be on the deep localization of PIM standards， PIM intervention and precise medication guidance， and PIM management of specific diseases and drugs.

Meta-analysis of clinical efficacy and safety of blinatumomab for acute lymphoblastic leukemia / 中国药房

OBJECTIVE To systema tically evaluate the efficacy and safety of blinatumomab for acute lymphoblastic leukemia （ALL）in order to provide evidence-based reference for clinical use. METHODS Retrieved from PubMed ，Embase，Web of Science，the Cochrane Library ，CNKI，Wanfang database and CBM during the inception to February 3，2022，randomized controlled trials （RCTs）and cohort studies of blinatumomab （experimental group ） versus conventional chemotherapy （control group ）in the treatment of ALL were collected. After literature screening and data extraction ，the quality of RCTs was evaluated by the risk bias evaluation tool recommended by Cochrane handbook 5.1.0，and the quality of cohort studies was evaluated by the Newcastle-Ottawa scale （NOS）. Meta-analysis was performed by RevMan 5.4 software. GRADE grading system was used to evaluate the evidence quality of outcomes. The publication bias was analyzed by inverted funnel plot. RESULTS A total of 8 studies were included ，involving 3 RCTs and 5 cohort studies ，with a total of 2 841 patients. Results of Meta-analysis showed that the overall survival rate more than one year [RR ＝1.30，95％CI（1.14，1.48），P＜0.000 1]，relapse-free survival rate [RR ＝1.78，95％CI（1.50，2.12），P＜0.000 01]，complete remission rate [RR ＝1.42，95％CI（1.11，1.82），P＝0.006]，the incidence of tremor [RR ＝16.98，95％CI（2.17，133.12），P＝0.007]，and the incidence of cytokine release syndrome [RR ＝14.11， 95％CI（3.43，58.01），P＝0.000 2] in trial group were all significantly higher than control group ，but there was no statistical significance in the incidence of headache between two groups [RR ＝1.31，95％CI（0.66，2.59），P＝0.44]. The incidence of adverse events with grade more than or equal to 3，infection，stomatitis，thrombocytopenia，febrile neutropenia ，anorexia， constipation，diarrhea，abdominal pain ，hypokalemia in trial group were significantly lower than control group （P＜0.05）. The incidence of cough ，rash and hypogamma globulinemia and fever in the trial group were significantly higher than control group （P＜0.05）. There was no statistical significance in the total incidence of adverse events ，sepsis，anemia，leucopenia，neutropenia， lymphopenia，nausea，vomiting，hyperglycemia，hypotension，hypertension，elevated transaminase or epistaxis between two groups（P＞0.05）. Results of subgroup analysis by study type showed that the overall survival rate ，relapse-free survival rate and complete response rate （except for cohort studies ）of patients in trial group were significantly higher than control group in both RCTs and cohort studies （P＜0.05）. The results of GRADE evaluation showed that the overall quality of index evidence included in this study was low. There was little possibility of publication bias in this study based on the publication bias analysis. CONCLUSIONS Blinatumomab is effective in the treatment of ALL ，with low incidence of infection and adverse events of digestive system ，but high incidence of tremor ，cough，rash，fever，hypoproglobulinemia and cytokine release syndrome. The evidence quality of the indicators included in this study is generally low .

Meta-analysis of Efficacy and Safety of Intranasal Administration of Dexmedetomidine versus Oral Administration of Chloral Hydrate for Programmed Sedation in Children / 中国药房

OBJECTIVE：To systematically evaluat e the efficacy and safety of intranasal administration of dexmedetomidine versus oral administration of chloral hydrate for programmed sedation in children. METHODS ：Retrieved from Cochrane Library ，PubMed， Embase，CBM，CNKI and Wanfang database ，randomized controlled trials （RCTs）about intranasal administration of dexmedetomidine （trial group ）versus oral administration of chloral hydrate （control group ）for programmed sedation in children were collected. Cochrane 5.1.0 bias risk assessment tool was used to evaluate the quality of the included literatures after literature screening and data extraction，and Meta-analysis was conducted by using Rev Man 5.3 statistical software. RESULTS ：A total of 8 RCTs were included ， with a total of 1 413 children. Meta-analysis showed that the sedation success rate [RR ＝1.13，95％CI（1.02，1.25），P＝0.02]，sedation onset time [MD ＝－1.07，95％CI（－1.82，－0.31），P＝0.006]，sedation duration [MD ＝－8.25，95％CI（－14.02，－2.47），P＝ 0.005]，wake-up time [MD ＝－9.63，95％CI（－15.40，－3.86），P＝0.001]，the incidence of nausea and vomiting [RR ＝0.05，95％CI （0.02，0.14），P＜0.000 01] in the trial group were significantly better than those in control group. There was no statistical significance in the incidence of SpO 2＜95％ [RR＝0.60，95％CI（0.24，1.54），P＝0.29]，incidence of hypotension [RR ＝1.18，95％CI（0.51， 2.74），P＝0.71]，incidence of bradycardia [RR ＝1.33，95％CI（0.18，9.88），P＝0.78] between 2 groups. CONCLUSIONS ：Intranasal administration of dexmedetomidine has better efficacy than oral administration of chloral hydrate for programmed sedation in children with good safety.

Meta-analysis of the Effectiveness and Safety of Low-molecular-weight Heparin Combined with Progesterone in the Treatment of Repeated Implant Failure in Embryo Transfer Patients / 中国药房

OBJECTIVE：To systematically evaluate the effectiveness and safety of low-m olecular-weight heparin combined with progesterone in the treatment of repeated implant failure （RIF）in embryo transfer patients ，and to provide reference for clinical use of it. METHODS ：Retrieved from Cochrane library ，PubMed，Embase，CNKI and Wanfang database ，randomized controlled trail （RCT）or observational study about low-molecular-weight heparin combined with progesterone （trial group ）versus progesterone（control group ）for RIF patients were collected during the inception to Jul. 2020. After data extraction of studies met included criteria ，the Cochrane 5.1.0 bias risk assessment tool and the Newcastle-Ottawa Scale evaluation scale were used to evaluate the quality of RCTs and observational studies. Rev Man 5.3 software was used for Meta-analysis. RESULTS ：A total of 15 studies were included ，including 10 RCTs and 5 observational studies ，with a total of 2 353 patients. Results of Meta-analysis showed that the implantation rate [RR ＝1.41，95％CI（1.24，1.60），P＜0.01]，pregnancy rate [RR ＝1.38，95％CI（1.23，1.56）， P＜0.01]，live birth rate [RR ＝1.41，95％CI（1.19，1.67），P＜0.01] of trial group were significantly higher than those of control group，with statistical significance ；while the abortion rate [RR ＝0.54，95％ CI（0.33，0.86），P＝0.01] of trial group was significantly lower than that of control group ，with statistical significance. The results of subgroup analysis showed that the implantation rate [RR ＝2.38，95％CI（1.31，4.31），P＝0.004] and pregnancy rate [RR ＝2.58，95％CI（1.62，4.11），P＜0.001] of patients over 35 years old in trial group were higher than control group ，with statistical significance. The main ADR of 2 groups were a small amount of bleeding and ecchymosis at the injection site. No severe ADR was observed. CONCLUSIONS： Low-molecular-weight heparin combined with progesterone can improve the embry o implantation rate ， pregnancy rate and live birth rate of RIF patients ，reduce the abortion rate ，with good safety.

Effects of CYP1A2 Gene Polymorphisms on Blood Concentrations of Antipsychotic Drugs ：A Meta-analysis / 中国药房

OBJECTIVE：To systematically evaluate the effects of CYP1A2 gene polymorphisms on blood concentrations of antipsychotic drugs （haloperidol，clozapine，olanzapine），and to provide evidence-based reference for the clinical drug use . METHODS：Retrieved from Cochrane Library ，PubMed，Embase，CBM，CNKI and Wanfang data ，during the inception to Nov. 2019，cross-sectional study was conducted to investigate the effects of CYP1A2 gene polymorphisms on blood concentrations of antipsychotic drugs （haloperidol，clozapine，olanzapine）were collected. After screening the literature ，extracting the data and quality evaluation with Q-Genie tool ，Meta-analysis was performed by using Rev Man 5.3 software. RESULTS ：A total of 11 cross-sectional studies were included ，with a total of 914 patients. Of these ，haloperidol was used in 2 studies，clozapine was used in 5 studies，and olanzapine was used in 4 studies. Meta-analysis showed that there was no statistically significant difference in the blood concentration of haloperidol between CYP1A2（－2964G＞A）G/G type and G/A+A/A type [SMD ＝－0.22，95％CI（－0.66， 0.23），P＝0.35]. The blood concentration of clozapine in CYP1A2（－163C＞A）A/C type was significantly lower than C/C type [SMD ＝0.31，95％CI（0.01，0.62），P＝0.04]；there was no statistical significance in blood concentration of clozapine between A/A type and C/C type [SMD ＝0.09，95％CI（－0.21，0.40），P＝0.56]，between A/A type and A/C type [SMD ＝－0.22，95％CI（－0.55， 0.10），P＝0.18]，between CYP1A2（－2467delT）delT/delT type and T/T type [SMD ＝－0.11，95％CI（－0.75，0.52），P＝0.72]， between delT/T type and T/T type [SMD ＝0.01，95％CI（－0.33，0.34），P＝0.97]，between delT/delT type and delT/T type [SMD ＝ －0.15，95％CI（－0.80，0.05），P＝0.66]. The blood concentration of olanzapine in CYP1A2（－163C＞A）A/A type was signifi- cantly lower than A/C type [SMD ＝－0.31，95％CI（－0.55， － 0.08），P＝0.009]；there was no statistically significant difference in the blood concentration of olanzapine between A/A liukefeng-num.1@163.com type and C/C type [SMD ＝－0.20，95％CI（－0.61，0.21），P＝ 0.34]，between A/C type and C/C type [SMD ＝0.06，95％CI E-mail：hnmuzj@163.com （－0.35，0.47），P＝0.77]，between CYP1A2（－2467delT）delT/T type and T/T type [SMD ＝0.28，95％CI（－0.15，0.71），P＝0.20]. CONCLUSIONS：CYP1A2（－163C＞A）A/C type is related to the reduction of clozapine blood concentration ，and A/A type is related to the reduction of olanzapine blood concentration. CYP1A2 （－163C＞A）gene polymorphism is significance for guiding individualized medication of schizophrenia patients.

Simultaneous Determination of 3 Impurities in Crude Drug and Preparation of Esomeprazole Sodium by LC-MS/MS / 中国药房

OBJECTIVE： To establish a method for simultaneous determination of impurity E， impurity Ⅰ and impurity Ⅳ in crude drug and preparation of esomeprazole sodium. METHODS： LC-MS/MS method was adopted. The separation was performed on Agela VenusiL MP C18 column with mobile phase consisted of acetonitrile-water （gradient elution） at the flow rate of 0.2 mL/min. The column temperature was 35 ℃， and the sample size was 1 μL； analytes were analyzed by electro-spray ionization （ESI） in the multiple reaction monitoring mode， negative ion. The precursors of production transitions m/z 360.1→194.0 （impurity E）， m/z 375.8→210.7 （impurity Ⅰ）， m/z 330.2→312.1 （impurity Ⅳ） were used to measure impurity. RESULTS： The linear range of impurity E， impurity Ⅰ and impurity Ⅳ were 0.001 26-0.044 80 μg/mL （r＝0.994 7）， 0.001 34-0.045 2 μg/mL （r＝0.992 8） and 0.018 9-1.260 00 μg/mL （r＝0.991 4）. The limit of quantitation were 0.001 26， 0.001 34， 0.018 9 μg/mL； the detection limits were 0.000 41， 0.000 44， 0.006 3 μg/mL. RSDs of precision and reproducibility tests were all lower than 4％； RSDs of stability tests of impurity E and impurity Ⅰ were all lower than 10％（n＝5）， and that of impurity Ⅳ was higher than 15％ （n＝7）. The average recoveries were 87.69％-100.72％ （RSD＝4.29％， n＝9）， 90.04％-100.63％（RSD＝3.67％，n＝9）and 93.58％-101.86％（RSD＝2.66％，n＝9）.  CONCLUSIONS： The method is accurate， rapid， sensitive， selective and suitable for the content determination of 3 impurities in crude drug and preparation of esomeprazole sodium.

Effects of olanzapine on glucose and lipidmetabolism, liver function and prolactin in childhood onset schizophrenia / 重庆医学

Objective To study the effects of olanzapine on glucolipid metabolism,liver function and prolactin level in childhood onset schizophrenia(COS) to provide reference for clinical medication.Methods Thirty-eight patients with COS aged 13-17 years old were treated with olanzapine for at least two weeks.The changes of body mass,alanine aminotransferase(ALT),aspartate aminotransferase (AST),total cholesterol (TC),triglyceride (TG),glucose (GLU) and prolactin (PRL) were detected and compared between before and after treatment.Results The body mass after medication in children patients was significantly increased,average increase by (3.50-t-1.90)kg (P＜0.01).The levels of ALT,AST,TC,TG and PRL after treatment were higher than before treatment (P＜0.05).However,there was no statistically significant difference in blood GLU level between before and after treatment(P=0.598).The body mass change before and after treatment was positively correlated with ALT and AST levels(r=0.366,0.377,P＜0.05);whereas the PRL level before and after treatment was negatively correlated with the body mass change (r=-0.432,P＜0.01).Conclusion Olanzapine can lead to the body weight gain and increase of ALT,AST,TC,TG and PRL levels in COS patients.

Change of (1,3)-β-D-glucan in tear before and after penetrating keratoplasty for fungal keratitis / 中华实验眼科杂志

Background Penetrating keratoplasty (PKP) has become an effective method of treatment for fungal keratitis in recent years,but the application timing of glucocorticoids after PKP is still unclear.Literature reported that the concentration of tear (1,3)-β-D-glucan in fungal keratitis was significantly higher than that in normal.Objective This study was to investigate the change of tear (1,3)-β-D-glucan before and after PKP in fungal keratitis and to explore the application duration of anti-fungal drugs and application timing of glucocorticoids.Methods This study protocol was approved by ethic committee of Affiliated Hospital of Qingdao University.A serial cases-observational study was performed from August,2011 to December,2012.Twenty eyes of 20 patients with fungal keratitis were collected in Affiliated Hospital of Qingdao University.PKP was performed in affected eyes,and the fellow health eyes served as controls.Tear of 50 μl was obtained in the controls on 1 day before operation and 1 day,7,14,21 and 28 days after operation to detect tear (1,3)-β-D-glucan levels.Results Tear (1,3)-β-D-glucan levels were (14.67±3.84)mg/L,(1 861.66±196.17) mg/L,(927.71±155.82)mg/L,(392.30±71.22)mg/L,(179.60±40.47) mg/L,(40.20± 12.46) mg/L and (15.12± 1.80) mg/L in the control group,preoperative 1 day,postoperative 1 day,7,14,21,28 days,respectively,showing a significant difference among various time points (F=883.45,P=0.00).Tear (1,3)-β3-D-glucan levels were gradually reduced with the lapse of the postoperative time,with significant differences between adjacent timepoints (t' =13.84,t =16.67,t' =11.02,t' =13.97,t' =-8.45,all at P=0.00).Tear (1,3)-β-D-glucan levels in postoperative 28 days came near that of normal control group,without significant difference between them (P =0.64).Fungal keratitis recurred in 2 eyes on the fifth and sixth day after operation,with the tear (1,3)-β-D-glucan levels of 2 350.24 mg/L and 1 992.82 mg/L,respectively.Conclusions The concentration of (1,3)-β-D-glucan in the tears increases in the eyes with fungal keratitis and drops to normal range at 28 days after PKP,indicating that the antifungal eyedrops should be applied until 4 weeks after PKP,and this is an optimal timing of using corticosteroid eyedrops to resist reject reaction.

Analysis on depression of patients with advanced schistosomiasis and its influ-encing factors / 中国血吸虫病防治杂志

Objective To explore the status of depression in patients with advanced schistosomiasis and its influencing fac-tors,so as to provide the evidence for improving psychological interventions. Methods A total of 206 patients with advanced schistosomiasis were investigated with the self-designed general information questionnaire,the Self-Rating Depression Scale,and WHOQOL-BREF Form. Results Among the 206 cases,the incidence of depression was 69.4%,and depression was negatively related to the quality of life(P = 0.000). The multiple logistic regression analysis showed that the times of hospitalization(β=0.442,P=0.007)was a risk factor for depression,while the high education levels(β=-0.583,P=0.011)and the history of por-tal hypertension operation(β=-0.917,P=0.000)were the protective factors. Conclusion The incidence of depression in ad-vanced schistosomiasis patients is high,and it is influenced by various factors. Therefore,we should take corresponding interven-tions to reduce its occurrence.

Analysis of Clinical Efficacy of Yiqing capsules and Cefaclor Tablets in Treatment of Simplex Anaphylactoid Purpura / 中国基层医药

Objective To investigate the efficacy of Yiqing capsules and Cefaclortablets in the treatment of simplex anaphylactoid purpura. Methods In this randomized,simple-blind, controlled study, all of 191 simplex anaphylactoid purpura patients,the throat secretion Group A βhemolytic streptococci antigen test was positive ,92 patients of control group were treated Cefaclor tablets and regular treatment,99 patients of test group were Yiqing capsules and Cefaclor tablets. Results After 10 days treatment,the clinical efficacy of the test group and the control group were 91.9% ,75.0% ,the test group was obviously higher than that of the control group(P ＜ 0.01), and the negative rate of the throat secretion Group A βhemolytic Streptococci antigen test of the test group was higher than that of control group, (P ＜0.01). the commencements of response of the test group was earlier than that of the control group(P ＜0. 01) ,the frequencies of recurrence of the test group were lower than that of the control group (P ＜ 0. 05).Conclusion Yiqing capsules combined cefaclor in treatment of simplex allergic purpura could improve efficacy, and reduce the treatment time.

A microscopic anatomy study of the retrosigmoid keyhole approach / 中国医师进修杂志

Objective To observe the microscopic anatomy structures of petroclival region via the retrosigmoid keyhole approach,then provide an anatomic basis for clinical application.Method Six adult cadaveric heads 6xed by 10% formaldehyde solution were used for simulating the retrosigmoid keyhole approach to observe major microscopic anatomy structures.Results By means of adjusting the microscope,structures such as the ipsilateral trigeminal nerves,cranial nerve,acoustic nerve,posterior nerves,anterior and lateral pons,lateral cerebellar hemisphere,anterior inferior cerebellar artery,vertebral artery,posterior inferior cerebellar artery were exposed via this keyhole approach.Conclusion This retrosigmoid keyhole approach is according with the minimally invasive principle,and represents a reasonable option for accessing the petroclival region.