Bupivacaine is a long-acting local anesthetic widely used clinically,but its 6-8 hours duration is insufficient for postoperative analgesia.Designing drug dosage forms to prolong the action time of local anesthetics is the research content of local anesthetics.In 2011,the FDA approved a bupivacaine liposome preparation based on DepoFoam TM technology:Exparel,which can be used for more than 72 hours.This article reviewed the clinical safety research of Exparel and the research progress of its application in clinical postoperative analgesia.

Objective To systematically evaluate whether taking calcium channel blockers(CCB)increases the risk of fractures. Methods Data were collected from Cochrane, PubMed, EMbase (OVID), CBM, VIP, CNKI and Wanfang databases.The Meta analysis was performed using RevMan5.2 software after evaluating the data quality. Results A total of 499 454 cases were included from 2 casecontrol studies and 2 cohort studies.Meta analysis showed no significant risk of fracture in patients taking CCB (OR＝1.23, 95% CI, 0.84-1.81, P＝0.29).Subgroup analysis showed that longterm treatment with CCB significantly decreased the risk of fractures (OR＝0.94, 95% CI, 0.92-0.96, P＝0.00), even though a trend of increased fracture risk existed in patients exposed to shortterm treatment (OR＝1.30, 95% CI, 0.83-2.03, P＝0.25). Conclusion Current evidence show that CCB administration does not increase the risk of fractures.The higher risk of fractures from short term use of CCB may result from the higher risk of falls,which remind us to improve the quality of nursing and strengthen selfawareness during the initial use of CCB.Restricted to the quantity and quality of literatures included, the Conclusion s are to be verified by more highquality studies.

Quality control of biotech drugs has attracted increasing attentions in recent years. Deamidation reaction is one of the major concerns in quality control of biotech drugs, due to the generation of isoaspartic acid(isoAsp). This paper describes the deamidation of asparagine(Asn) residues and its effects on the biological drugs. The detection methods currently used in China and overeas for this reaction, including pretreatment protocols and instrumental analysis were described. The identification and determination of isoaspartyl sites were also described in detail, along with the positive impact on the development of biotech drugs in China by the studies on deamidation reactions.

Objective To study clinical application and safety of quetiapine fumarate in treating Alzheimer’s disease (AD). Methods A total of 74 patients with AD were randomly divided into treatment group(n=48)and control group(n=26).Patients in the control group were given 5 mg·d^-1 of donepezil chloride,patients in the treatment group were given 5 mg·d^-1 of donepezil chloride and 12.5 mg·d^-1 of quetiapine fumarate.Before and 1,2,4,8 and 12 weeks after the treatment,the patients were evaluated by mini-mental state examination(MMSE),the brief psychiatric rating scale(BPRS),neuropsychiatric inventory(NPI),NPI distress factor and activity of daily life(ADL). Results After 1 week of treatment,total NPI score of treatment group and control group was(72.830±10.45) and(78.057±10.97),respectively;NPI distress factor was(30.532±5.82) and(34.208±6.50),respectively(all P<0.05).After 4 weeks of treatment,BPRS scores of treatment group and control group was(30.277±6.43) and(35.01±7.38),respectively(P<0.05).After 8 weeks of treatment,NPI distress factor of treatment group and control group was(23.021±5.74) and(28.618±6.08)(P<0.05).After 12 weeks,MMSE score of treatment group and control group was(7.83±3.02) and(7.116±2.67),which was increased compared with that before treatment(all P>0.05). Conclusion Short-term use of quetiapine fumarate can reduce anguish of AD tender,and relieve psychological and behavioral symptoms of AD patients,and may have positive effects on cognitive function.

摘要目的分析双氯芬酸钠所致不良反应，为临床安全、合理用药提供参考。 方法检索《中国医院数字图书馆》中有关双氯芬酸钠引起不良反应的文献资料（1994～2011年），按年龄、性别、剂量、合用药物、给药方法、药品不良反应发生时间分布、临床表现症状、治疗与转归进行统计分析。 结果双氯芬酸钠引起的不良反应与性别关系不大，年龄分布以41～60岁为主。所致的不良反应类型以泌尿系统损害（26.1%）和消化系统损害（23.9%）为主；前3位的表现形式为急性肾衰竭、血尿、消化道出血；发生时间以第1天发生不良反应为主，占58.7%。 结论要严密观察患者使用双氯芬酸钠时的异常反应，发现问题及时停药、及时处理，警惕严重不良反应（急性肾衰竭、血尿、过敏性休克）的发生，确保患者的用药安全。

With the gradual promotion of drug selection and evaluation in some provinces and cities in China,it is urgent for medical institutions to establish a complete and quantifiable drug selection and evaluation system. Based on the development of pharmacy and the adjustment of national drug policies in recent years,this guideline has revised and refined the evaluation indicators of drug evaluation and selection in medical institutions on the basis of the first version,so that the quantitative scoring can better reflect the priority of drugs in medical institutions,and also more fulfill the requirements of the national policy. Moreover,the scoring items are more detailed,clear and easy to use. In this guideline,five dimensions of pharmaceutical properties (28 points),effectiveness (27 points),safety (25 points),economy (10 points) and others (10 points) were quantified and scored,so as to objectively conduct selection and evaluation of drugs in medical institutions.

由美国辉瑞制药有限公司研制的劳拉替尼(lorlatinib)是第三代非小细胞肺癌(NSCLC)治疗新药,具有间变性淋巴瘤激酶(ALK)和c-ros原癌基因1(ROS1)双重受体酪氨酸激酶(RTK)抑制作用,用于治疗既往接受过至少一种ALK抑制药治疗,但病情进展的ALK阳性和(或)ROS1阳性转移性NSCLC患者。美国食品药品管理局(FDA)于2015年10月授予lorlatinib罕用药(orphan drug)认定,2017年4月27日获得FDA突破性治疗药资格和优先审评的待遇,并于2018年11月2日加速批准上市,制剂商品名为Lorbrena ^®;日本医药品医疗器械综合机构(PMDA)于2018年9月21日批准该药上市,片剂商品名为ロルラチニブ^®;欧洲药品管理局(EMA)人用药品委员会(CHMP)2019年2月底财政年度会议纪要中,对lorlatinib的安全性和有效性持正面意见,建议EMA批准上市,制剂商品名将命名为Lorviqua^®。该文对lorlatinib非临床和临床药理毒理学、临床研究、不良反应、适应证、剂量与用法、用药注意事项及知识产权状态和国内外研究进展等进行介绍。

Medication-related harm poses a severe threat to patient safety.To address the challenges of medication safety,the World Health Organization (WHO) has launched a global initiative with the theme "Medication without Harm" and adopted "Medication without Harm" as the slogan for this year's World Patient Safety Day.Since 2016,WHO has focused on medication safety and developed strategic frameworks and action plans to address medication safety challenges.The International Pharmaceutical Federation (FIP) has worked closely with WHO on patient safety issues,advocated for the active role of pharmacists in the medication use process,and assisted WHO in publishing technical reports on three key areas to identify priority areas for action.This paper reviews the key measures of WHO and FIP in addressing medication safety challenges to provide a reference for the development of medication safety practices in China.

Objective To construct a set scoring criteria for the evaluation and selection of oral nonsteroidal anti-inflammatory drugs( NSAIDs)for clinical analgesia,to ensure the scientific and standardized development of the comprehensive clinical evaluation on oral NSAIDs,to the foundation for the comprehensive clinical evaluation on other drugs. Methods According to authoritative guidelines and drug instructions,the Delphi expert consultation method was subjected to seek expert opinions and establish an expert consensus on the evaluation and selection scoring criteria of oral NSAIDs,and use this criteria to score 6 oral NSAIDs. Results This study quantitatively scored from six dimensions: safety,efficacy,economy,accessibility,innovation,and suitability.The total scores from high to low were celecoxib capsules,meloxicam tablets,etoricoxib tablets,diclofenac sodium sustained-release tablets,ibuprofen sustained-release capsules,and imrecoxib tablets. Conclusion Guided by clinical value,a scientific and standardized evaluation and selection criteria of oral NSAIDs for clinical analgesia has been established to strengthen pharmaceutical management in medical institutions,while promoting the rational use of drugs.

Through literature review,questionnaire surveys,medical case analysis and other methods,Chinese Hospital Association Pharmaceutical Specialized Committee conducted research on the current status and development direction of pharmacy administration and pharmacy practice in healthcare institutions,summarized systematically the key issues in the fields of pharmacy practice,pharmaceutical supply services and pharmacy administration in healthcare institutions,studied relevant domestic and foreign literature in recent years,referenced existing domestic laws,regulations and rules,as well as domestic and foreign standards,and ultimately established a group standard system framework.The group standard system was named “Pharmacy administration and Pharmacy practice in Healthcare institutions”,and included 51 volumes in four parts,which were general principles,pharmacy practice,pharmaceutical supply services and pharmacy administration.

The “Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions” was developed by standards-based process from WHO.The guideline was referenced to the WHO Essential Medicines List,WHO Medicines and Health Products Programme Strategic Framework (2016—2030),and the relevant policy and system documents of developed countries and regions,including the United States, Europe, Japan and so on.Experts reached consensus on the scoring system for drug evaluation and selection were reached through the Delphi method in this guideline.In the end, to develop this guideline, we also took the actual conditions of Chinese medical institutions into account.

Objective By analyzing the evolution of China's national pharmaceutical packaging material standards,the significance of pharmaceutical packaging material standards in ensuring drug safety,effectiveness,and accessibility is summarized,providing a reference for constructing the national pharmaceutical packaging material standard system. Methods Through reviewing the development process of national pharmaceutical packaging standards in China's pharmaceutical industry at different stages and under different regulatory models,the experience and shortcomings of establishing a national pharmaceutical packaging standard system in China were summarized. Results The national pharmaceutical packaging materials standard system in China has been closely followed by the development and regulatory needs of the pharmaceutical industry,continuously enhancing its connotation and sublimated its concept;The national pharmaceutical packaging material standard is an important guarantee for promoting the high-quality development of the pharmaceutical packaging material industry.The standard system of pharmaceutical packaging materials can effectively improve the quality of pharmaceutical packaging materials and ensure the safety,effectiveness,and accessibility of drugs only if it follows the changes of the new situation and constantly improves itself. Conclusion Drawing on the development trend of domestic and foreign pharmaceutical packaging materials and related field standard systems,establishing risk management concepts and full process management concepts based on ensuring drug safety and effectiveness,and accelerating the construction of a scientific,advanced,practical,and standardized national pharmaceutical packaging material standard system is an important task in the construction of Chinaese national pharmaceutical packaging material standard system.

Cancer is a severe threat to human life and health.The over-activation of oncogenes is the main reason for poor treatment and prognosis of cancer patients.Most of these over-activated oncogenes are protein tyrosine kinase (PTK).Among many PTKs,non-receptor tyrosine kinase (NRTK) is an important signaling molecule that regulates cell proliferation and migration as the primary driver of intracellular signaling pathway transduction. Targeting NRTK has become the focus and difficulty in developing anti-tumor drugs.Traditional Chinese medicine (TCM),with its characteristics of multi-channel,multi-link,multi-target,and low toxicity,plays a significant advantage in treating adjuvant tumors.So far,it has been found various traditional TCM monomers can inhibit NRTK from playing an anti-tumor role.This review summarized the part of Src,Jak,Abl,Fak families,the prominent members of NRTK in tumor progression,as well as the TCM monomers acting on these members. We aimed to provide a theoretical basis for the anti-tumor therapy targeting NRTK and a reference for the search for TCM monomer inhibitors of NRTK.

Icariin,which belongs to the class of flavonoids,is the main active ingredient of the traditional tonic Chinese herb Epimedii Folium.Modern studies have shown that icariin has a wide range of effects on the male reproductive system.It has various pharmacological activities such as regulating cell proliferation and apoptosis,antioxidants,promoting testosterone secretion,improving erectile function,inhibiting prostate cancer cell migration,invasion,and regulating cell cycle.It has research value and application prospects in the field of urology and assisted reproduction.Therefore,Icariin's pharmacological effects and molecular mechanisms on the male reproductive system are reviewed in this paper combined with literature visualization analysis.It is expected to provide a theoretical basis for the therapeutic value development and application of icariin in male reproductive health.

Objective To study the preparation process of compound Xiecao shuxin dropping pills. Methods Dropping pills were prepared by dropping method.The effects of PEG4000/6000 matrix, drug-matrix ratio, dropping acceleration and liquid temperature on the preparation of the dropping pills were studied.Orthogonal test was conducted with the total scores of appearance, weight difference, and dissolution time as the factors to optimize the best preparation process of compound Xiecao shuxin dropping pills. Results The optimal preparation process of compound Xiecao shuxin dropping pill was as follows: PEG4000/6000 (1:1) was as the matrix, and the ratio of drug to matrix was 1:3.The temperature of the feeding liquid was 90 ℃, and the dropping acceleration was 35 drops per minute, and the temperature range of condensate liquid paraffin was from 5 to 15 ℃. Conclusion The optimized preparation technology is stable and feasible, which can provide necessary reference for the preparation of compound Xiecao shuxin dropping pills.

As a new method of drug combination therapy,drug-drug cocrystals can optimize the physicochemical properties of drugs,give play to the synergistic and dual drug therapeutic effects,and overcome the defects in traditional combination drugs without changing the chemical structure of the active components of the drug.In recent years,drug-drug cocrystal has been a hot research topic in solid chemical drug.This paper reviewed the design and prediction methods of drug-drug cocrystal,and the preparation methods and application advantages,to provide some reference for the subsequent application in drug research and development.

恩格列净(empagliflozin)由美国礼来公司和德国勃林格殷格翰公司合作研发,是钠葡萄糖共转运蛋白2(SGLT2)抑制药,用于改善2型糖尿病成年患者的血糖控制,对二甲双胍耐受性差、靠调节饮食与锻炼不能有效控制血糖的成年患者,可单药治疗或与其他降血糖药物联合用药. 该文对恩格列净的非临床和临床药理毒理学、临床研究、适应证、剂量与用法、用药注意事项、不良反应及知识产权状态和国内外研究进展等进行介绍.

Nanocarriers of skin functional ingredients have wide applicable prospects in transdermal drug delivery and cosmetics,with good effects of diseases treatment and skin care.This article introduces the characteristics of nanocarriers for skin functional ingredients and reviews the research progress on the nanocarriers for skin diseases treatment,barrier repairing,melanin inhibition,antioxidation,and anti-acne etc.

ObjectiveTo provide evidence for clinical trial and to evaluate the safety of total flavonoids from rhizome of drynariae MethodsThe maximum tolerance of gastrogavage in mice: twenty mice were fed 30 mL·kg^-1 with the total flavonoids solution (0.40 g·mL^-1 ) by gastrogavage， the bite and sup， activity， psychosis， coat and skin， urine and faeces， and body weight were observed The maximum tolerance of gastrogavage in rats: twenty rats were given the same dose total flavonoids solution， and the same observation were done The acute toxicity trial in mice, LD50 was carried out by abdominal injection with 7 dosage groups， and the mice were observed for 7 days after one injection ResultsThe mice and rats had no abnormal changes in bite and sup， activity， psychosis， coat and skin， urine and faeces， and body weight There were no significant changes(P＞0.05) Only a little remain of the fed sample was found in the abdomen anatomizing And there were no remarkable pathological changes in all organs The median lethal dose of the total flavonoids was 5.99 g·kg^-1 ConclusionThere are no abnormal changes in the acute toxicity trial with total flavonoids from rhizome of drynariae, and the flavonoids are safe in clinical use

The “Tangye Jingfa map” of Fuxingjue contains a complete syndrome differentiation and treatment system,including disease diagnosis and herbal treatment.In terms of disease diagnosis,“Tangye Jingfa map” respects the syndrome differentiation on deficiency and excess syndrome of Five Zang only,and determines the disease nature based on the deficiency and excess syndrome of liver,heart,spleen,lungs,and kidneys.The 20 prescriptions for tonifying or reducing Five Zang included in Fuxingjue,which clearly records the clinical manifestations of deficiency and excess syndrome of Five Zang.This paper summarizes and analyzes the records of the main symptoms of the prescriptions for tonifying and reducing Five Zang in Fuxingjue,standardizes and equivalently converts the description of syndromes,and unifies the description of different syndromes,such as “pain leads to less abdominal urgency” and “less abdominal fullness and pain”,“irritability” and “heart deficiency”.At the same time,the diagnosis information database of deficiency and excess syndromes of Five Zang was constructed.It was found that there were overlaps of indications between the syndrome of small Decoction and large Decoction in the same Zang (such as the small Decoction of tonifying liver and the large Decoction of tonifying liver),and between the syndrome of large tonifying Decoctions in the adjacent Zang (such as the large Decoction of tonifying spleen and the large Decoction of tonifying lung).Using C4.5 algorithm and random tree algorithm of the decision tree discrimination model,we can also get the diagnosis discrimination model of the deficiency and excess syndrome of Five Zang,and identify the key symptom nodes.Through the above research,it provides academic support for the clinical application of syndrome differentiation and treatment theory shown in “ Tangye Jingfa map ”.

The pathogenesis of depression is highly complicated and has not been fully elucidated.Numerous clinical and preclinical studies suggested that serotonergic (5-HT) neurological dysfunction critically contributed to depression.In addition to the serotonin transporter (SERT),multiple subtype receptors in the 5-HT nervous system are related to depression.Among them,5-HT_1A and 5-HT_2A receptors are most closely associated.Brain widely distributed 5-HT_2A receptors provide a fundamental basis for regulating mood and perception.5-HT_2A receptors modulate the level of monoamine transmitters in the brain by directly or indirectly regulating monoamine transmitters' release to participate in depression development.5-HT_2A receptors antagonists enhanced the therapeutic effects of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) for treatment-resistant depression and reduced adverse reactions such as sexual dysfunction and sleep disorder.Several 5-HT_2A receptor-targeted antidepressants were approved for clinical treatment,and many compounds are currently being researched in clinical or preclinical studies.This review briefly discussed the relationship between 5-HT_2A receptors and depression and summarized the research progress of antidepressants targeting 5-HT_2A receptors to provide information for antidepressant research.

To determine whether mirtazapinne is clinically effective on the treatment of chronic insomnia and to compare the clinical effects between mirtazapine and alpazolam on chronic insomnia. MethodsSeventynine patients were randomly divided into two groups (38 and 41 for each), which received the treatments of mirtazapine and alprazolam respectively for 12 weeks as a course. The patients in mirtazapine group took 10－15 mg 0.5 hour before sleeping, while the patients in alpazolam group took 0.4－0.8 mg 0.5 hour before sleeping. The curative effects were evaluated with Pittsburgh Sleep Quality Index (PSQI) and sleeping dairy before and after the 4th, 8th, and 12th weeks of treatment. ResultsThe effective rate and significantly effective rate of mirtazapine on chronic insomnia were 96.9% and 90.6%, respectively, whereas those of alprazolam, 78.8% and 51.5% respectively. Mirtazapine played significantly better role in the treatment of chronic insomnia than alprazolam did(P＜0.05). The side effects of mirtazapine included sleepy, dizzy and getting weight, all of which were acceptable. ConclusionMirtazapine is surely effective on clinical treatment of chronic insomnia with mild side effects . For using mirtazapine, starting with the small dosage is suggested.

To assess the therapeutic effectiveness and safety rate of gatifloxacin hydrochloride in the treatment of infections of the respiratory or urinary system. Methods225 patients with infections of the respiratory or urinary system were randomly divided into 2 groups: the trial group (n＝114) and control group (n＝111). Patients of the trial group were given each 0.4 g of gatifloxacin hydrochloride tablets PO,q.d. while those of the control group were given each 0.2 g of levofloxacin, PO, b.i.d.. The course of treatment in both groups lasted 7－14 days. The therapeutic effectiveness and adverse reactions of the drugs were kept under observation. ResultsIn patients of the trial group and control group, the clinical effective rates were 88.60% and 92.79%, the bacteria elimination rates were 94.32% and 96.63% and the incidences of adverse reactions were 9.32% and 11.97%, respectively. Differences between the 2 groups with respect to the above mentioned data were insignificant (P＞0.05). ConclusionGatifloxcin hydrochloride was shown to be effective and safe in the treatment of infections of the respiratory or urinary system.

L-carnitine is a carrier that assist in transport of long-chain fatty acids into mitochondria and an effective drug for treating primary carnitine deficiency (PCD).Starting supplementation as early as possible before irreversible organ damage occured can alleviate organ damage,reduce the risk of sudden death,and improve the quality of life.However,in recent years,some studies have suggested that long-term oral L-carnitine has potential risks,the metabolism of L-carnitine through intestinal flora results in the production of trimethylamine oxide (TMAO),which can increase the risk of cardiovascular disease (CVD).Therefore,this paper summarizes the clinical research progress of L-carnitine in treating PCD to provide a theoretical basis for the clinical application of L-carnitine in PCD.

［摘要］综述治疗泌尿系统结石（石淋）的10种基本中成药，介绍祖国医学对石淋的认识和研究，并归纳和总结现代医学对中药治疗泌尿系统结石的化学、药理和临床疗效研究。由经验方制成的中成药因具有疗效确切、价格低廉及使用方便的特点，具有良好的临床应用前景。但部分单味中药治疗结石的有效成分和药理至今尚不明确，少数中成药的临床研究报道较少，需加强国家基本药物的研究和应用。

Objective To analyze the development status of intelligent pharmaceutical services for traditional Chinese medicine,to summarize the practical experience of intelligent pharmaceutical services for traditional Chinese medicine,and to explore its technical requirements and development direction. Methods The Affiliated Hospital of Chengdu University of traditional Chinese medicine launched the Smart Traditional Chinese Medicine Room project in January 2018 and established a Smart Traditional Chinese Medicine Pharmacy to undertake pharmaceutical services such as outpatient dispensing,decoction,and distribution of traditional Chinese medicine decoction pieces. Results A total of 5.572 million pairs of traditional Chinese medicine decoction pieces were delivered until May 2023,and 231 400 patients were served in 2022.The service process was more straightforward;there was no need to wait for medication or go to the hospital again.The service efficiency was high,improving the patient's medical experience. Conclusions Intelligent pharmaceutical services for traditional Chinese medicine are developing rapidly.A comprehensive intelligent service system will be established based on technological progress in the future.