Objective To analyze the effectiveness and safety of bisphosphonates in the treatment of pa-tients with calcification defense.Methods PubMed,Embase databases,CNKI and Wanfang were searched to collect the case reports and clinical studies of bisphosphonates for calcification defense.Then,the relevant infor-mation of patients was extracted for statistical analysis.Results A total of 18 case reports were selected involving 20 patients.Thirteen patients(65.0％)were treated with pamidronate,four(20.0％)were treated with etidr-onate,two(10.0％)were treated with alendronate,and one(5.0％)was treated with zoledronic acid.Thirteen patients(65.0％)recovered completely,the recovery time of whom ranged from half month to nine months.The tolerance of bisphosphonates in most patients(90.0％)was good,while one patient who did not tolerate pamidr-onate recovered after the frequency of administration was adjusted and one patient with high dosage of etidronate returned to normal after the discontinuation of the usage.Conclusions Bisphosphonates,an inhibitor of bone resorption,is effective and safe in the treatment of patients with calcification defense.

Transthyretin(TTR) protein is a tetramer protein, synthesized mainly by the liver. TTR can be misfolded and deposited as amyloid fibrilae and deposited in the myocardial interstroma leading to transthyroxin amyloidosis cardiomyopathy (ATTR-CM). ATTR-CM was included in China's First List of Rare Diseases. Therapeutic strategies for ATTR-CM include blocking TTR synthesis in the liver, stabilizing TTR tetramers and destroying TTR fibra. Small molecule drugs such as tafamidis and diflunisal offer new treatment options for patients. Chlorobenzolic acid became the first drug approved by the U.S. Food and Drug Administration for the treatment of ATTR-CM. Small interfering RNA(siRNA)patisiran and antisense oligonucleotide (ASO)inotersen block TTR expression in the liver and have been approved for the treatment of ATTR variant polyneuropathy (ATTRv-PN)and are in phase Ⅲ trials for the treatment of ATTR-CM. Other siRNA drugs, vutrisiran, and ASO, eplontersen, are being evaluated for clinical efficacy. This article reviews the development of RNA-targeted therapeutics and gene-editing drugs using CRISPR-Cas9.

A 78-year-old female patient with atrial fibrillation developed tarry stools after regularly taking dronedarone, metoprolol, and rivaroxaban for 3 months. The patient stopped using rivaroxaban by herself for 7 days, and her black stools was gradually improved. After taking rivaroxaban again for 1 month, black stools appeared again, accompanied by fatigue, dizziness, and amaurosis fugax. Her blood pressure was 90/50 mmHg, heart rate was 80 beats/min, and hemoglobin was 55 g/L. Rivaroxaban was discontinued again and supportive treatments such as soft food, acid suppression, fluid replacement, and blood transfusion were given. After 3 days of treatments, the symptoms of fatigue were improved significantly, and no amaurosis recurred when sitting up. Hemoglobin was 75 g/L. After 6 days of treatments, the patient discharged formed yellow soft stools. After excluding gastrointestinal tumors through gastroscopy and tumor marker examination, it was considered that the interaction of dronedarone and rivaroxaban caused the increase of rivaroxaban plasma concentration, which resulted in gastrointestinal bleeding in the patient. The patient′s anticoagulant medication was changed to dabigatran etexilate, and no gastrointestinal bleeding occurred.

Anaphylaxis is a severe, life-threatening, immediate, and systemic allergic reaction, and may lead to serious consequences due to delayed diagnose or improper treatment. Guidelines at home and abroad recommend epinephrine as a first-line treatment for anaphylaxis. But there are still some problems such as insufficient use, inappropriate administration route or dosage of epinephrine in the treatment of anaphylaxis in China. The timing (as early as possible), route (intramuscular injection is preferred), and dosage of epindphrine should strictly follow the recommendations of relevant guidlines. Epinephrine autoinjectors can win more rescue time for patients with anaphylaxis, and can be equipped and used after training by clinicians.

A 78-year-old female patient with atrial fibrillation developed tarry stools after regularly taking dronedarone, metoprolol, and rivaroxaban for 3 months. The patient stopped using rivaroxaban by herself for 7 days, and her black stools was gradually improved. After taking rivaroxaban again for 1 month, black stools appeared again, accompanied by fatigue, dizziness, and amaurosis fugax. Her blood pressure was 90/50 mmHg, heart rate was 80 beats/min, and hemoglobin was 55 g/L. Rivaroxaban was discontinued again and supportive treatments such as soft food, acid suppression, fluid replacement, and blood transfusion were given. After 3 days of treatments, the symptoms of fatigue were improved significantly, and no amaurosis recurred when sitting up. Hemoglobin was 75 g/L. After 6 days of treatments, the patient discharged formed yellow soft stools. After excluding gastrointestinal tumors through gastroscopy and tumor marker examination, it was considered that the interaction of dronedarone and rivaroxaban caused the increase of rivaroxaban plasma concentration, which resulted in gastrointestinal bleeding in the patient. The patient′s anticoagulant medication was changed to dabigatran etexilate, and no gastrointestinal bleeding occurred.

Anaphylaxis is a severe, life-threatening, immediate, and systemic allergic reaction, and may lead to serious consequences due to delayed diagnose or improper treatment. Guidelines at home and abroad recommend epinephrine as a first-line treatment for anaphylaxis. But there are still some problems such as insufficient use, inappropriate administration route or dosage of epinephrine in the treatment of anaphylaxis in China. The timing (as early as possible), route (intramuscular injection is preferred), and dosage of epindphrine should strictly follow the recommendations of relevant guidlines. Epinephrine autoinjectors can win more rescue time for patients with anaphylaxis, and can be equipped and used after training by clinicians.

Remote pharmaceutical care refers to the process that pharmacists provide pharmaceutical care to patients remotely through information technology. Remote pharmaceutical care in China starts late and develops slowly. Therefore ，this paper discusses the pharmaceutical care modes that pharmacists at home and abroad can provide under the remote mode by collecting literature. The results show that foreign remote pharmaceutical care starts early and is relatively mature. The service mainly included remote follow-up and intervention ，24-hour online prescription and order review ，24-hour online drug reorganization ，and guidance on rational drug use in remote areas or community hospitals. The service population covers patients with cardiovascular disease ， diabetes，asthma，AIDS and so on. Some hospitals have established an integrated pharmaceutical care system of “Internet+Medical Consortium”in China ，with which pharmacists can provide patients with pharmaceutical care such as remote follow-up and intervention，drug consultation and so on. With the promotion of telemedicine ，domestic pharmacists can gradually expand the scope of services ，expand pharmaceutical services such as remote consultation and remote popular science push ，and realize the sharing of high-quality pharmaceutical care for the whole people.

Off-label drug use is a global problem in clinical practice. The management status, attitude and medical insurance coverage of off-label drug use are different in various countries. By analyzing the management and reimbursement policy of off-label drug use in other countries, the authors suggested that China should speed up the institutional arrangements of off-label drug use and establish relevant management systems, and strengthen the supervision of off-label drug use, so as to guarantee the rights of patients to the best treatment.

OBJECTIVE：To o ptimize the t ype of nervous system medicines in National Essential Medicine List of China. METHODS：Various editions of WHO Essential Medicine Model List （WHO EML ）were consulted ，the collection of nervous system medicines was analyzed statistically ，and 2017 edition of WHO EML was compared with 2018 edition of National Essential Medicine List of China （NEML）. RESULTS ：During 1977-2017，the total number of nervous system medicines and disease coverage included in each edition of WHO EML had little change. Compared with 2017 edition of WHO EML ，2018 edition of NEML contained more medicines for nervous system disease （54 medicines vs. 30 medicines），and covered more disease types ， such as dementia （huperzine A ）and neuralgia （pregabalin），etc. However ，for the treatment of multiple sclerosis ，neuralgia， dementia and other diseases ，there were not many medicines to choose ，and some similar medicines （with the same or similar mechanism of action ）were collected repeatedly and some medicines had serious adverse reaction. CONCLUSIONS ：It is suggested that National Essential Medicine List should be continuously optimized and perfected ，the varieties of essential medicines for the treatment of nervous system diseases should be increased appropriately ，for improving the treatment effect of such diseases and reducing the cost burden of patients.

Vascular calcification is a process similar to bone de-velopment, which is excessively abnormal deposition of calcium and phosphate in blood vessel wall. It is a sign of early athero-sclerosis formation, and can reduce the atherosclerotic vascular compliance. The common regulation of vascular calcification is affected by many factors. This article discusses the formation of vascular calcification from the molecular mechanism, the chemi- ＜br> cal mechanism and metabolic factors. It also reviews the progress of the prevention of vascular calcification by traditional Chinese medicine.