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《广州医药》编辑部

广州医药杂志服务号
论著

基于数据挖掘和网络药理学研究中枢性性早熟的用药规律和作用机制

Research on the prescription rules and mechanism of central precocious puberty based on data mining and network pharmacology

:500-512
 
目的 运用数据挖掘、网络药理学和分子对接的方法,探讨中药复方治疗中枢性性早熟(CPP)的用药规律和作用机制,为其临床治疗提供更多依据。方法 在中国知网(CNKI)、万方数据(Wanfang)、维普中文期刊(VIP)等数据库中检索从建库至2022年10月发表的中药复方治疗CPP的文献,用Excel 2021 收集整理临床治疗CPP的常用中药复方,并通过Excel 2021、SPSS Modeler 18.0、SPSS Statistics 25.0等软件对其进行频次、关联规律等分析,研究CPP治疗的用药规律。在上述基础上采用网络药理学的研究方法,筛选出高频药对的活性成分、作用靶点以及疾病的相关靶点,构建蛋白互作网络,并通过基因本体和京都基因 基因组百科全书通路富集分析来阐明药物的作用机制。最后运用 Autodock Vina 软件进行分子对接对结果验证。结果 共筛选出224篇文献,包含方剂133首,中药188味。发现18味使用超过25次的高频药物;清热类、补虚类的药物应用较多;药物性味以寒及苦为主;归经之中以肝经占比最高;进一步关联分析得到高频药对14个;核心处方4个。网络药理学结果显示,共得到44个活性成分、200个药物靶点、1 287个疾病靶点、70个共有靶点、573条GO富集条目及136条KEGG通路,药物主要成分槲皮素、山奈酚、β-谷甾醇作用于雌激素受体、黄体酮受体等核心靶点,通过内分泌抵抗、雌激素等信号通路发挥治疗作用。分子对接结果显示药物主要活性成分与相应核心靶点具有较好的结合能力。结论 中药复方治疗CPP多为滋阴清热、补虚类药物,与药性寒,药味苦、甘,归肝、肾经的药物配伍使用。其中高频药对“知母-黄柏”通过多成分、多靶点调控内分泌抵抗、雌激素信号通路发挥治疗作用。
Objective To explore the prescription rules and mechanism of traditional Chinese medicine(TCM) in the treatment of central precocious puberty(CPP)by using data mining,network pharmacology and molecular docking,so as to provide more evidence for clinical treatment.Methods Using the literature on the treatment of CPP with TCM compounds,which was retrieved from the databases of CNKI,Wanfang,VIP and other databases from the establishment of the database to October 2022 as the data sources.Excel 2021 was used to collect and summarize the commonly used TCM prescriptions for CPP,and conducted frequency analysis and association rules analysis of CPP by Excel 2021,SPSS Modeler 18.0,SPSS Statistics 25.0 and other software,so as to study the composition rule of prescriptions for CPP.On the basis of these results,network pharmacology method was used to screen out the active ingredients and action targets of high-frequency drugs,and then screen out the disease related targets to construct PPI network.Mechanism of drugs was clarified through GO and KEGG pathway enrichment analysis.Finally,the molecular docking of autodock Vina(Vina)platform was used to verify the results.Results A total of 244 documents met the search criteria,including 133 prescriptions and 188 traditional Chinese medicines.It had been found that 18 high-frequency Chinese medicines were used more than 25 times.The drugs mainly focused on clearing heat and supplementing deficiency.The medicinal flavors were mainly cold and bitter,which belonged to the liver channel.Further correlation analysis yielded 14 high-frequency drug pairs and 4 core prescriptions.The results of network pharmacological analysis showed that 44 active components,200 drug targets,1 287 disease corresponding targets,70 common targets,573 GO enrichment entries and 136 KEGG pathways targets were obtained.It has been found that the main components of the drugs,such as quercetin,kaempferol and β-sitosterol,act on the core targets of ESR1,PGR and play a therapeutic role through endocrine resistance and estrogen signaling pathways.Finally,molecular docking results showed that the main active ingredients of the drug had good binding ability with the corresponding core targets.Conclusions In the treatment of CPP,traditional Chinese medicine is mainly used types of nourish Yin,clear heat and replenish deficiency,which is compatible with the drugs with cold properties,bitter and pliant taste,and the liver and spleen channels.Among them,high-frequency drug pair “ZhiMu-HuangBai” play a therapeutic role in the regulation of endocrine resistance and estrogen signaling pathways through multi-components and multi-targets.
护理研究

远程药学管理模式联合延续护理在2型糖尿病合并冠状动脉病变患者居家用药中的研究

Study on home medication of type 2 diabetes patients with coronary artery disease by remote pharmaceutical management mode combined with continuous nursing

:427-431
 
目的 探讨远程药学管理模式联合延续护理在2型糖尿病(T2DM)合并冠状动脉病变患者居家用药中的应用效果。方法 选取2021年6月—2023年6月在广州医科大学附属第三医院诊治的200例T2DM合并冠状动脉病变患者为研究对象,根据干预方式不同分为常规组100例和研究组100例。常规组患者给予院内院外常规护理,研究组在常规组的基础上给予远程药学管理模式联合延续护理。评估患者用药依从性、饮食依从性、运动依从性、自我管理能力、生活质量[36条目简明健康量表(SF-36)]及心血管事件发生情况。结果 研究组用药、饮食、运动依从性均高于常规组(P<0.05)。相较于干预前,两组患者在干预后的自我管理机能、自我责任感、自我概念及健康知识分值均升高,且研究组高于常规组(P<0.05)。相较于干预前,两组患者在干预后的活力(VT)、精神健康(MH)、情感职能(RE)、躯体疼痛(BP)、生理功能(PF)、社会功能(SF)、生理职能(RP)、总体健康(GH)分值均升高,且研究组高于常规组(P<0.05)。研究组与常规组患者心血管不良事件发生率分别为2例(2.00%)、15例(15.09%),研究组高于常规组(χ2=10.865,P<0.05)。结论 远程药学管理模式联合延续护理能够提高T2DM合并冠状动脉病变患者的用药管理依从性,提高患者自我管理能力,改善生活质量,降低不良心血管事件的发生率。
Objective To explore the application effect of remote pharmacy management mode combined with continuous nursing in the home medication of type 2 diabetes mellitus(T2DM)patients with coronary artery disease.Methods A total of 200 patients with T2DM complicated with coronary artery diseases who were diagnosed and treated in the Third Affiliated Hospital of Guangzhou Medical University from June 2021 to June 2023 were selected as the study subjects.They were divided into a conventional group of 100 patients and a study group of 100 patients based on different intervention methods.The patients in the conventional group received routine care both in and out of the hospital,while the study group received remote pharmaceutical management mode combined with continuous care on the basis of the conventional group.Patient medication compliance,dietary compliance,exercise compliance,self-management ability,quality of life[36 item concise health scale(SF-36)] and incidence of adverse cardiovascular events were assessed.Results The compliance of medication,diet and exercise in the study group were significantly higher than those in the conventional group(P<0.05).Compared to before intervention,the self-management function,sense of responsibility,self-concept and health knowledge scores of both groups of patients were significantly increased after intervention,and the scores of the study group were significantly higher than those in the conventional group(P<0.05).Compared to before intervention,the Vitality(VT),Mental Health(MH),Emotional Function(RE),Physical Pain(BP),Physiological Function(PF),Social Function(SF),Physiological Function(RP)and Overall Health(GH)scores of both groups of patients were significantly increased after intervention,and the scores of the study group was significantly higher than those of the conventional group(P<0.05).The incidence of cardiovascular adverse events in the study group and the conventional group were 2 cases(2.00%)and 15 cases(15.09%),respectively,with the study group significantly higher than the conventional group(χ2=10.865,P<0.05).Conclusions The combination of remote pharmaceutical management mode and continuous care can significantly improve the medication management compliance of T2DM patients with coronary artery disease,improve their self-management ability,improve the quality of their life and reduce the incidence of adverse cardiovascular events.
临床诊疗

氨溴索静脉用药联合不同通气方式治疗新生儿呼吸窘迫综合征的疗效评价

:76-79
 
目的 研究氨溴索静脉用药联合不同通气方式治疗新生儿呼吸窘迫综合征(NRDS)的临床疗效。方法 选取2019年2月—2021年1月我院收治的98例NRDS患儿,根据治疗方案不同分为对照组(49例)和观察组(49例)。2组均给予常规治疗,对照组采用氨溴索静脉用药、常规机械通气治疗,观察组采用氨溴索静脉用药、高频振荡通气(HFOV)治疗。比较2组临床疗效、胸部X线评分、新生儿评分(Apgar评分)、不同时间点(治疗前、治疗后2 h、治疗后12 h)动脉血气指标[氧合指数(OI)、动脉氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)]、呼吸力学指标[呼吸指数(RI)、呼吸道阻力(R)、肺动态顺应性(Crs)]、并发症发生率、死亡率。结果 2组治疗后总有效率比较,观察组93.88%高于对照组77.55%(P<0.05);治疗后,观察组胸部X线评分、Apgar评分均高于对照组(P<0.05);治疗后2 h、治疗后12 h时观察组OI、PaCO2均低于对照组,PaO2高于对照组(P<0.05);治疗后,观察组RI、AR水平低于对照组,Crs水平高于对照组(P<0.05);观察组死亡率2.04%低于对照组14.29%(P<0.05)。结论 氨溴索静脉用药联合HFOV治疗NRDS的临床疗效显著,可有效促进患儿呼吸功能、动脉血气改善,降低新生儿死亡率。
论著

基于中药处方数据挖掘探索中医药治疗盆腔炎用药规律

Exploration on regularity of traditional Chinese medicine for pelvic inflammatory disease based on large data mining of Chinese herbal medicine prescriptions

:72-80
 
目的 探究中医药治疗盆腔炎的用药规律,为中医临床辩证用药提供借鉴。方法 采用主题词联合自由词相,全面检索CNKI、VIP、Wangfang、CBM、PubMed和EMbase、数据库及Cochrane图书馆,收集中、西药对比治疗盆腔炎的随机对照试验。严格按照纳入、排除标准挑选随机对照试验中涵盖的中药药方,采用Excel表格统计分析药方中药的四气、五味、归经和用药频率,随后利用系统聚类软件对使用频率高的中药开展关联、聚类和主成分分析。结果 本文共纳入235个随机对照试验,涉及320首中药处方,平均用药味数13.29味,使用频率前五位的药分别为延胡索、赤芍、当归、蒲公英、丹参;关联规则共得出41对高关联药对,其中包括赤芍-延胡索、莪术-三棱-败酱草等。高频率使用的前30味中药可分为五大类,获取的9个主成分分析结果与系统聚类中的结果一致。结论 本研究采用循证医学和系统聚类分析方法,剖析中医药治疗盆腔炎的用药规律,为临床用药提供参考。
Objective To discuss the medication regularity of traditional Chinese medicine (TCM) in the treatment of pelvic inflammatory disease, and provide new thinking for effective medication in clinical medicine. Methods Keywords combined with free word were used to comprehensively search CNKI, VIP, Wangfang, CBM, PubMed and EMbase, databases and Cochrane library to collect randomized controlled trials of comparative treatment of pelvic inflammatory disease between Chinese and Western drugs. The TCM prescriptions covered in the randomized controlled trial were selected in strict accordance with the standard inclusion and exclusion criteria. Excel was used to statistically analyze the four properties, five flavors, meridian and medication frequency of TCM prescriptions. Then, systematic clustering software was used to carry out correlation, clustering and principal component analysis for the Chinese medicines with high using frequency. Results The study included 235 randomized controlled trial and 320 prescriptions of traditional Chinese medicine were involved, the average number of herbs was 13.29, which Yanhusuo, Chishao, Danggui, Pugongying, Danshen were with top five frequency. A total of 41 drug pairs with high association were obtained by association rules, including Chishao-Yanhusuo, Eshu-Sanleng-Baijiangcao, etc. Thirty traditional Chinese medicine with high using frequency can be divided into 5 categories according to the effect. The obtained results of 9 principal component analysis were consistent with those in the system cluster. Conclusions In this study, evidence-based medicine and systematic cluster analysis were used to analyze the medication regularity of traditional Chinese medicine in the treatment of pelvic inflammatory disease, so as to provide reference for the clinical medication.
论著

药物服务干预对老年高血压患者的治疗及用药安全性的影响

Influence of drug service intervention on the treatment and drug safety of elderly patients with hypertension

:49-54
 
目的 探讨药物服务干预对老年高血压患者的治疗及用药安全性的影响。方法 选取2020年6月—2021年12月潮州市中医药研究所门诊部和潮州市中医医院高血压患者90例为研究对象,采用随机数字表法分为观察组45例(给予药物服务干预),对照组45例(给予常规用药指导)。比较干预后血压控制水平、健康知识认知、治疗依从性、自我管理行为、生活质量及药物不良反应等情况。结果 干预后,观察组舒张压、收缩压、不良反应发生率均低于对照组(P<0.05)。干预后,观察组健康知识认知水平、治疗依从率、自我管理行为评分、生活质量评分均高于对照组(P<0.05)。结论 采用药物服务干预的方式能够较好控制老年高血压患者血压水平,提升其健康知识认知水平与治疗依从性,改善自我管理行为状况,提高生活质量。
Objective To investigate the effect of drug service intervention on the treatment and drug safety of elderly patients with hypertension.Methods From June 2020 to December 2021,a total of 90 patients with hypertension from Chaozhou Institute of traditional Chinese Medicine and Chaozhou Hospital of Traditional Chinese Medicine were selected as the study objects,and were divided into observation group(45 cases,given drug service intervention)and control group(45 cases,given routine drug guidance)by random number table method.The blood pressure control level,health knowledge cognition level,treatment compliance,self-management behavior,quality of life and adverse drug reactions of elderly patients with hypertension were compared after intervention.Results After intervention,the incidence of diastolic blood pressure,systolic blood pressure and adverse drug reactions in the observation group were lower(P<0.05).After intervention,the health knowledge cognition level,treatment compliance rate,self-management behavior score and quality of life score of the observation group were higher(P<0.05).Conclusions The use of drug service intervention can better control the blood pressure level of elderly patients with hypertension,improve their health knowledge cognition and treatment compliance,improve self-management behavior and improve quality of life.
论著

基于中国PIM标准分析老年精神疾病住院患者潜在不适当用药现状

Analysis of potentially inappropriate medication in elderly psychiatric inpatients based on criteria of potentially inappropriate medication for the elderly in China

:57-61
 
目的 调查分析老年精神疾病住院患者潜在不适当用药(PIM)现状。方法 回顾分析2021年3月老年住院患者临床诊断、用药情况等资料,依据2017年版《中国老年人潜在不适当用药判断标准》分析处方PIM情况。结果 125例研究对象中,平均年龄(73.31±7.87)岁,平均用药(6.62±2.68)种。101例(80.80%)患者存在140项PIM,81例(64.80%)患者使用了A级警示药物共103项,33例(40.74%)患者使用了B级警示药物共37项;高风险药物39项(27.86%),低风险药物101项(72.14%);PIM发生率排名前3位的药物是奥氮平、利培酮、劳拉西泮;12例患者存在4项与疾病状态相关的PIM。结论 该院PIM发生率偏高,医生和药师应加大力度降低PIM比例,减少不良反应,提高用药安全,促进合理用药。
Objective To investigate the current status of potentially inappropriate medications (PIM) for elderly inpatients with mental illness in a psychiatric hospital. Methods Based on the 2017 edition of “Judgment Standards for Potentially Inappropriate Medications for the Elderly in China”, we retrospectively analyzed the PIM by investigating the clinical diagnosis and medication status of 125 elderly psychiatric inpatients in March 2021. Results Among 125 subjects, the average age was (73.31±7.87) years, and the average medication was (6.62±2.68). There were 101 patients (80.80%) had 140 items of PIM, 81 patients (64.80%) used a total of 103 items of A-level warning drugs, 33 patients (40.74%) used a total of 37 items of B-level warning drugs; there were 39 high-risk drugs(27.86%), 101 low-risk drugs (72.14%); the drugs with top three PIM incidence were olanzapine, risperidone and lorazepam; 12 patients had 4 PIMs related to the disease state. Conclusions The incidence of PIM in this hospital is relatively high. Doctors and pharmacists should be advised to increase their efforts to reduce the proportion of PIM, reduce the incidence of adverse reactions, improve medication safety, and promote rational drug usage.
论著

家庭药师与药物治疗管理对签约患者用药依从性及不合理用药干预效果

Intervention effects of family pharmacists and medication management on medication compliance and unreasonable medication use of contracted patients

:79-82
 
目的 探讨家庭药师与药物治疗管理对签约患者用药依从性及不合理用药干预效果。方法 选取2017年3月—2021年3月我院收治的慢性病患者100例作为前瞻性研究对象,按照随机余数法分为对照组和研究组各50例。其中,对照组实施首次随访调查,收集患者健康信息建立用药档案,末次随访评价。研究组采用收集患者健康信息,建立用药档案,填写调查表,对在用的药物治疗方案进行评价,家庭药师与家庭医生协作共同干预或直接干预,制定具体的解决方案,帮助患者达到治疗目标。比较2组患者干预前后的药物依从性、生活质量及用药情况的变化。结果 干预前,2组患者的药物依从性评分比较无统计学意义(P >0.05),干预后,2组患者药物依从性评分比较随时间增加而改善,而研究组的药物依从性评分显著高于对照组,统计学显示差异有统计学意义(P<0.05)。2组患者的选择合理、给药频率合理、滴定合理、换药合理、联合用药合理均有明显改善且研究组多于对照组,比较差异有统计学意义(P<0.05)。结论 家庭药师及药物治疗管理干预能够有效提高患者用药依从性及生活质量,改善用药情况,对慢性病患者干预具有一定参考价值。
Objective To explore intervention the effect of family pharmacist and medication management on medication compliance and unreasonable drug use in contracted patients. Methods A total of 100 patients with chronic diseases from March 2017 to March 2021 in our hospital were selected as prospective study subjects. According to the random remainder method,they were divided into control group and research group with 50 cases in each group. Among them,the control group was surveyed in the first followed-up,and the health information of patients was collected to establish drug use files,and evaluation was performed in the final follow-up. Family pharmacists and family physicians intervened together or directly to formulate specific solutions to help patients achieve the treatment goals and explain the treatment goals. The changes of medication compliance,quality of life and drug use before and after intervention were compared between the two groups. Results Before the intervention,the medication compliance scores of the two groups were not significantly different (P>0.05).After the intervention,the medication compliance scores of the two groups improved with time,while the medication compliance scores of the research group were significantly higher than the control group,statistics analysis showed that the difference was significant (P<0.05).The reasonable selection,the reasonable frequency,the reasonable titration,the reasonable drug change,and the reasonable combined medication in research group were significantly more than the control group,and the differences were statistically significant (P<0.05).Conclusions Family pharmacist and medication management intervention could effectively improve medication compliance and quality of life of patients,improve drug use,had a certain reference value for chronic disease patients.
论著

某精神病院取消药品加成前后精神药物的用药分析

Analysis of antipsychotics use before and after abolishing additional cost of drugs in a psychiatric hospital

:59-64
 
目的 分析广州市某精神病院住院病人精神药物用药的情况变化,为该类药物药费控制、合理应用和科学管理提供参考。方法 统计2015年7月15日—2019年7月14日精神药物的销售金额、用药频度、日用药金额并进行分析。结果 该院4类精神药物共40种,抗精神病药销售金额先升后降,DDDs小幅度增加,非典型抗精神病药销售金额占97%以上,DDDs占87%以上;抗抑郁药销售金额和DDDs逐年增长,新型抗抑郁药占99%以上;抗焦虑药销售金额先升后降;心境稳定药销售金额先升后降,DDDs小幅度减少;65%精神药品排序比趋近1;62%精神药品DDDc下降;取消加成后,销售总金额减少,DDDs总和却增加。结论 取消药品加成对抗精神病药影响较大,对抗抑郁药、抗焦虑药以及心境稳定药影响较小;药品零加成可明显减轻患者经济负担,促进用药合理化。
Objective To analyze the changes in the use of psychotropic drugs by inpatients in a psychiatric hospital in Guangzhou, and to provide reference for the control, rational application and scientific management of the drugs. Methods The sales amount, frequency of use, and daily use of psychotropic drugs from July 15, 2015 to July 14, 2019 were counted and analyzed. Results There were a total of 40 kinds of psychotropic drugs of 4 types in this hospital. In the past 4 years, the sales of antipsychotic drugs increased first and then decreased, and DDDs increased slightly. The sales amount of atypical antipsychotic drugs accounted for more than 97% of the total drug cost, and DDDs accounted for more than 87%. The sales amount of antidepressants DDDs were increasing year by year, and new generation antidepressants account for more than 99% of the antidepressants. The sales of anti-anxiety drugs increased first and then decreased. The sales of mood stabilizer increased first and then decreased, and DDDs decreased slightly. 65% of psychotropic drug's rank closes to 1. DDDc in 62% of the psychotropic drugs decreased; after abolishing additional cost of drugs, the total sales amount decreased, but the total DDDs increased. Conclusion Abolishing additional cost of drugs had a greater impact on antipsychotic drugs, but little effect for antidepressants, anxiolytics, and mood stabilizers, which may greatly reduces patient's drug cost and promote rational use of drugs.
论著

我院静脉用药调配中心2017—2019年不合理医嘱分析

Analysis of irrational prescriptions in pharmacy intravenous admixture services of our hospital from 2017 to 2019

:95-100
 
目的 对我院静脉用药调配中心2017年1月—2019年12月期间的不合理医嘱情况进行汇总及分析,以提高合理用药水平。方法 收集2017年1月—2019年12月广州市第一人民医院静脉用药调配中心的不合理医嘱资料进行回顾性分析,归纳不合理医嘱类型、汇总分析不合理医嘱表现以及改正不合理情况。结果 主要不合理医嘱类型包括溶媒选择错误、溶媒量过多或过少、药物剂量不合理、药物配伍禁忌、其他(用药频次错误、药物选择错误、重复用药等)。结论 根据不合理医嘱情况的汇总分析,及时与临床科室沟通改正,保证合理用药。
Objective To summarize and analyze their rational prescriptions in pharmacy intravenous admixture services(PIVAS)of our hospital from January 2017 to December 2019,so as to improve the level of rational drug use. Methods The data of irrational prescriptions from January 2017 to December 2019 in the pharmacy intravenous admixture services of Guangzhou First People's Hospital were collected for retrospective analysis, and the types of irrational prescriptions were summarized, the performance of irrational prescriptions was analyzed and the irrational situation was corrected. Results The main types of irrational prescriptions include incorrect selection of solvent, improper consumption of solvent, improper drug dosage, incompatibility and others(improper frequency of administration, incorrect selection of drug, repeated administration, etc.). Conclusion According to the summary and analysis of irrational prescriptions, we timely communicate with clinical departments and ensure rational drug use.
论著

中医治疗胎动不安的用药规律

Analysis on traditional Chinese medicine of fetal irritability

:48-53
 
目的 统计分析中医治疗胎动不安的用药规律,为临床中医治疗胎动不安提供用药参考。方法 严格按照标准筛选中医治疗胎动不安的中药处方,采用 excel表格对处方基本用药信息进行统计,然后再采用 SPSS19.0软件以中药的功效作为评价指标进行分析,以确定处方中用药味数、用药天数、以及中药的使用频次。并对使用频次前30位的药物进行归类,确定药物使用频次高的特征值、贡献率和综合得分。结果 所选取的356例患者中药处方中,平均用药药味数15.7味,平均剂量226.7 g,使用频次最高的前5位药分别为菟丝子、桑寄生、续断、白芍、白术;30味中药通过按照功效可分为5类,所提取的10个主成分能反映系统聚类中的分类结果。结论 对中医治疗胎动不安患者处方进行分析,为中医治疗胎动不安提供了用药参考,对指导临床合理用药有重要指导意义。
Objective To analyze the medication experience in treating fetal irritability and provide medication reference of clinical traditional Chinese medicine in treatment of fetal irritability. Methods The prescription of traditional Chinese medicine treats was screened according to the standard. The information of prescription basic were statisticed with Excel and processed the data by SPSS19.0, to determine the frequency of medicine the number of drugs and medication days. The Chinese medicines used in the top 30 were classified to determine the characteristic of eigenvingue,rate of contribution and synthesis score. Results The top 5 highest frequency medicines were Tusizi, Sanjisheng, Xuduan, Baishao, Baishu; and the average drug taste was 15.7,the average dose was 226.7 g,after analyzing the screened 356 prescriptions. 30 Chinese medicines could be clustered into 5 kinds. The extraction of 10 principal components of principal component scores and comprehensive scores may reflect the classification results of system clustering. Conclusion To analyze the prescriptions of traditional Chinese medicine for fetal irritability, provide the reference for medicine combination in treating different syndromes of fetal irritability. It had the extremely vital significance for guiding the clinical medication.
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