Analysis and thinking on the practice of local regional drug online procurement in China / 中国药房

OBJECTIVE To systemically sort out the main practices of local drug online procurement， so as to provide reference for national and local governments to improve drug online procurement policies and drug price formation mechanism. METHODS By searching the official websites of 31 provincial medical security bureaus and drug-centralized procurement platforms in China， the classification methods and main goals of local drug online procurement were summarized， then the main practices of local drug online procurement were analyzed based on the main goals， and corresponding suggestion was put forward. RESULTS & CONCLUSIONS There were two classification methods of online drug procurement in each province， one is based on online or purchase methods， and the other is based on drug dimensions. Five main objectives of online drug procurement in each province are to ensure reasonable drug prices， meet clinical drug demand， ensure stable drug supply， cooperate with the implementation of drug policies， and standardize the behavior of transaction subjects. In order to achieve the five goals， each province has taken some targeted measures， but the severity of the policy varies greatly. In order to further improve the online drug procurement policy and improve the market-oriented online drug price formation mechanism， it is suggested to build the top-level design of online drug procurement， strengthen the management of the price comparison relationship of similar drugs， give full play to the monitoring function of the drug-centralized procurement platform and establish a national unified drug-centralized procurement platform.

Effects of regular aerobic exercise on brachial ankle pulse wave velocity in middle-aged and elderly people / 中华老年医学杂志

Objective:To investigate the effects of regular aerobic exercise on brachial ankle pulse wave velocity(baPWV)in middle-aged and elderly people.Methods:This was a cross-sectional study.A total of 7993 subjects receiving health examination at the Taihu Sanatorium of Jiangsu Province were enrolled, including 4 371 males and 3 622 females, with an average age of 55.8 years(±7.9).Information on exercise, alcohol consumption, smoking, body mass index, baPWV, blood pressure, resting heart rate, fasting blood glucose, total cholesterol(TC), triglycerides(TG), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C)and uric acid in all subjects were collected and recorded.Based on exercise habits, subjects were divided into the no exercise group(n=489), the occasional exercise group(n=3 222, exercise<3 times or<90 min per week)and regular exercise group(n=4 282, exercise 3-5 times or >90 min per week).Results:For male subjects, differences in baPWV between the no exercise group(1 747.37±346.07 cm/s), the occasional exercise group(1 486.77±195.15 cm/s)and the regular exercise group(1 449.77±219.50 cm/s)were statistically significant( P<0.05).For female subjects, difference in baPWV between the no exercise group(1865.05±120.19)cm/s, the occasional exercise group(1 593.18±332.51)cm/s and the regular exercise group(1 227.81±150.89)cm/s were also statistically significant( P<0.05).With increased time of exercise per week, the levels of systolic blood pressure, diastolic blood pressure, resting heart rate, fasting blood glucose, TG and uric acid in different exercise groups decreased gradually for both men and women.Multivariate linear regression analysis showed that exercise, alcohol consumption, systolic blood pressure, diastolic blood pressure and fasting blood glucose were independent risk factors for baPWV in men(all P<0.05)and that exercise, systolic blood pressure, diastolic blood pressure, resting heart rate and fasting blood glucose were the independent risk factors for baPWV in women(all P<0.05).Trend analysis showed that with increased time of exercise per week, the rate of abnormal baPWV decreased gradually in both men and women( χ2 values were 74.67 and 1545.54, respectively, P<0.01). Conclusions:Regular aerobic exercise can improve baPWV, systolic blood pressure, diastolic blood pressure, resting heart rate, fasting blood glucose, TG and uric acid in middle-aged and elderly people.Exercise is an independent influencing factor for baPWV in middle-aged and elderly people and exercise 3-5 times or more than 90 min per week is beneficial to cardiovascular health in middle-aged and elderly people.

Mechanistic analysis for the origin of diverse diterpenes in Tripterygium wilfordii

Tripterygium wilfordii is a valuable medicinal plant rich in biologically active diterpenoids, but there are few studies on the origins of these diterpenoids in its secondary metabolism. Here, we identified three regions containing tandemly duplicated diterpene synthase genes on chromosomes (Chr) 17 and 21 of T. wilfordii and obtained 11 diterpene synthases with different functions. We further revealed that these diterpene synthases underwent duplication and rearrangement at approximately 2.3-23.7 million years ago (MYA) by whole-genome triplication (WGT), transposon mediation, and tandem duplication, followed by functional divergence. We first demonstrated that four key amino acids in the sequences of TwCPS3, TwCPS5, and TwCPS6 were altered during evolution, leading to their functional divergence and the formation of diterpene secondary metabolites. Then, we demonstrated that the functional divergence of three TwKSLs was driven by mutations in two key amino acids. Finally, we discovered the mechanisms of evolution and pseudogenization of miltiradiene synthases in T. wilfordii and elucidated that the new function in TwMS1/2 from the terpene synthase (TPS)-b subfamily was caused by progressive changes in multiple amino acids after the WGT event. Our results provide key evidence for the formation of diverse diterpenoids during the evolution of secondary metabolites in T. wilfordii.

Research progress in role and mechanism of neutrophils in tissue repair / 中华创伤杂志

Damage to skin, muscle, bone and nerve tissues can result in various degrees of damage to the body, leading to organ dysfunction even life-threatening. To restore the structure and function of the damaged tissues, various immune cells and histocytes have successively participated in the tissue repair process. As the terminally differentiated white blood cells, neutrophils can remove necrotic tissue, debris and pathogens via phagocytosis and release of antimicrobial peptides after tissue injury to provide conditions for subsequent tissue repair process. However, enhanced neutrophils recruitment as well as excessive inflammatory response may also aggravate tissue damage. In recent years, more and more evidences indicate that neutrophils display plasticity and heterogeneity and that play critical roles in the initiation of tissue repair, promotion of angiogenesis, regulation of cell proliferation and so on. Herein, the authors review the recruitment, phenotype and function, role and outcome of neutrophils during tissue repair so as to provide references for future studies.

Effect of Tanhuo Formula on the expression of Caspase-3, GFAP, and angiogenesis in rats with cerebral ischemia / 国际中医中药杂志

Objective:To study the effect of Tanhuo Formula (THW) on the expression of Glial Fibrillary Acidic Protein (GFAP), Caspase-3 and angiogenesis.Methods:Rats were divided into sham group, model group, low-dose THW group, medium-dose THW group, high-dose THW group and Ginaton group according to random number table method. Except the sham group, rats in other groups were subjected to the middle cerebral artery occlusion via a suture method. After 2 hours,rats in the low, medium and high dose of THW groups were gavaged with 0.92, 1.84 and 3.68 g/kg of THW dry extract powder solution respectively, and the Ginaton group were gavaged with 60 mg/kg of Ginaton, once every 24 hours for 3 days. Rats in sham operation group and model group were given equal volume of normal saline by gavage. The limb symmetry score was used to evaluate limb dysfunctions. The immunofluorescence staining of GFAP and Caspase-3 were applied to assess astrocyte activation and neuronal apoptosis, respectively. The double-labeled immunofluorescence staining of platelet-endothelial cell adhesion molecule (CD31) and chondroitinsulphate peoteoglycan (NG2) were performed to detect angiogenesis.Results:Compared with the model group, rats in the high-dose of THW group showed increased limb symmetry score ( P<0.01 or P<0.05), increased number of Caspase-3 (cortex: 765.0±122.4 vs. 1 131.0±392.9; striatum: 895.9±389.8 vs. 1 401.9±453.1) ( P<0.01 or P<0.05) and CD31 +/NG2 + (cortex: 1 355.0±257.9 vs. 825.4±308.1; striatum: 1 290.9±400.9 vs. 675.2±259.7) ( P<0.01) positive cells in the periinfarct cortex and striatum, and attenuated the integrated optical density of GFAP in the perilesional cortex (4 210.00±1 226.38 vs. 7 935.78±2 001.98) ( P<0.01). Conclusions:THW could ameliorate the limb functional disorders, inhibit astroglia activation, down-regulate the expression of Caspase-3, and enhanced angiogenesis in MCAO rats.

Study of health state disutility value estimation of malignant tumor drugs-related adverse events ：a systematic review / 中国药房

OBJECTIVE To provide methodology re ference for conducting health state disutility estimation and calculating health output in pharmacoeconomic evaluation. METHODS Literatures about health state disutility estimation of malignant tumor drugs-related adverse events were retrieved from 3 Chinese databases such as CNKI ，Wanfang database and VIP and 3 English database such as PubMed ，Web of Science and the Cochrane Library from inception to July 2021. After 2 researchers independently screened the literature and extracted the data ，qualitative analysis was conducted. The modified decision-making technical support documents of the National Institute for Health and Care Excellence were used for quality evaluation. The practice and existing problems of health state disutility measurement were summarized to put forward some suggestions. RESULTS A total of 77 literatures were included. The first literature was published in 1991，and the number of publications increased in a fluctuating manner. 77 literatures involved 120 kinds of adverse events ，mainly utility studies （49，63.64％），only 3 （3.90％） were investigated in China. A total of 35 literatures（45.45％）had no statement of study design type ，48（62.34％）had no statement of health status development method ，52（67.53％）had no statement of health status verification method ，46（59.74％）set and explained the basic health status ，and 20（25.97％）were ranked for the health status . The utility measurement tools used were mainly the standard game method and the European five-dimensional health scale （23 literatures each ，accounting for 29.87％）. The research objects of 45 literatures（58.44％）were patients ，and 63（81.82％）did not specify the representative test of the population. Utility report types included negative value ，non-negative value and non-negative value of consolidated basic status. A total of 45 literatures（58.44％）had no statement of statistical method of utility. Overall quality score of included studies was 0.683. CONCLUSIONS The current disutility estimation include 4 key links of basic study design ， health status confirmation， utility estimation survey and survey data E-mail：luyuqiong96@foxmail.com statistics. The deficiencies of related studies are the lack of data based on the Chinese population ，the inconsistent type ofresult reporting ，and the incomplete report of measurement- related critical items. It is recommended to standardize the basic implementation path of disutility estimation ，formulate guidelines for health status utility value estimation ，and strengthen multidisciplinary cooperation so as to improve the quality of health status utility value estimation .

Postoperative ileus after laparotomy for gastrointestinal cancer treated with electroacupuncture: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on postoperative ileus after laparotomy for gastrointestinal cancer.@*METHODS@#A total of 90 patients with postoperative ileus after laparotomy for gastrointestinal cancer were randomized into an EA group and a conventional treatment group, 45 cases in each one. In the conventional treatment group, the postoperative fast track surgical regimen was accepted. In the EA group, on the base of the treatment as the conventional treatment group, acupuncture was applied to Zusanli (ST 36), Shangjuxu (ST 37), Yinlingquan (SP 9) and Taichong (LR 3) and electric stimulation was attached on Zusanli (ST 36) and Yinlingquan (SP 9), with continuous wave, 2 Hz in frequency and 3-5 mA in intensity. Acupuncture was provided once daily till the onset of postoperative exhaust and defecation. The first postoperative exhaust time, the first postoperative defecation time, the postoperative hospital stay and the wound pain under standing on the next morning after entering group were compared in the patients between the two groups. The impact of the EA expectation was analyzed on the first postoperative exhaust time, the first postoperative defecation time and the postoperative hospital stay separately.@*RESULTS@#The first postoperative exhaust time and the first postoperative defecation time in the EA group were earlier than the conventional treatment group (P<0.05), the postoperative hospital stay was shorter than the conventional treatment group (P<0.05), and the rate of wound pain in the postoperative standing was lower than the conventional treatment group (P<0.05). EA expectation had no obvious correlation with the clinical therapeutic effect (P>0.05).@*CONCLUSION@#EA can relieve postoperative ileus symptoms, alleviate pain and shorten hospital stay in the patients after laparotomy for gastrointestinal cancer.

Research on merging methods and influencing factors of health state disutility values estimation ：taking diarrhea caused by antitumor drugs as an example / 中国药房

OBJECTIVE To explore the merging methods and influencing factors of health state disutility values estimation. METHODS Retrieved from 6 Chinese and English databases such as CNKI and PubMed ，the literatures about disutility values of diarrhea caused by antitumor drugs were collected from the inception to July 2021. After 2 researchers independently screened the literature，extracted the data ，assessed the quality ，the Meta-analysis and regression analysis were conducted using Stata 16.0 software. RESULTS Fifteen literatures were included. The results of Meta-analysis showed that diarrhea caused by antitumor drugs had a significant impact on health utility [ MD＝－0.26，95％CI（－0.30，－0.22），P＜0.05]. The results of subgroup analysis showed that the disutility values of the 3 types of negative value ，non-negative value changed into negative value ，and non-negative value combined with basic state changed into to negative value were MD ＝－0.14，95％CI（－0.19，－0.09）；MD＝－0.46，95％CI （－0.56，－0.36）；MD＝－0.12，95％CI（－0.20，－0.05），respectively. Meta regression results showed that the year of publication ， survey country/region ，severity of adverse events ，basic state settings ，utility estimation tools ，utility report types ，and utility statistical methods significantly affected the value of diarrhea disutility （P＜0.05）. CONCLUSIONS Disutility values for treatment-related symptoms or complications should be fully considered when inputting the parameters to the economic evaluation model. In the study or application of disutility values ，the types of utility reports should be distiguished ，and the core influencing factors such as the investigation country or region ，the severity of symptoms or complications ，and whether the basic state is set should be focus on.

Effects of cardiovascular health behaviors and factors on postmenopausal osteoporosis in Suxichang area of Jiangsu province / 中华老年医学杂志

Objective:To explore the relationship of cardiovascular health behavior and factors with development of bone mass loss and postmenopausal osteoporosis in Suxichang area of Jiangsu province.Methods:In the across sectional study, a total of 2 423 postmenopausal women receiving health check-up from March 2019 to June 2020 in our hospital were enrolled.The seven variable factors included cardiovascular health behavior(body mass index, exercise, healthy diet and smoking state)and cardiovascular health-influencing factors(blood pressure, fasting blood glucose and total cholesterol). The information of the seven factors and bone mineral density were recorded.The seven factors were classified as ideal, average and poor, according to the level of bone mineral density.All individuals were divided into three groups: normal bone mass(n=1 305), osteopenia(n=290)and osteoporosis(n=828).Results:There were statistically significant differences in age, fasting blood glucose, systolic blood pressure, diastolic blood pressure, total cholesterol and exercise between osteoporosis and normal bone mass group( P<0.05). As the number of ideal cardiovascular health behaviors and factors increased, the proportion of bone mass loss and osteoporosis gradually decreased( P<0.05). Multiple logistic regression analysis showed that ageing, increased total cholesterol and fasting blood glucose levels were the independent risk factors of osteoporosis.The exercise and normal body mass index were the protective factors for osteoporosis.For each 1 unit increment in age, total cholesterol, body mass index and fasting blood glucose, the OR values for bone mineral density decrement by 1 grade were 1.17, 1.25, 0.92 and 1.23, respectively(all P<0.05). The OR value for bone mineral density decrement by 1 grade was 0.58( P<0.05)when exercise decreased by 1 grade. Conclusions:Postmenopausal women should positively control the levels of total cholesterol and fasting blood glucose, maintain reasonable body weight and conduct regular exercise, which are conductive to the prevention and treatment of postmenopausal osteoporosis.

Identification and functional characterization of 2,3-oxidosqualene cyclase genes family in Tripterygium wilfordii / 药学学报

italic>Tripterygium wilfordii Hook. f. is a valuable medicinal plant, with anti-tumor, anti-inflammatory, immunosuppressive and other pharmacological activities. Triterpenoids are one of the main active components that exert pharmacological effects. However, the content of triterpenoids dominated by triptolide is very low in Tripterygium wilfordii, and the analysis of the biosynthetic pathway of triterpenoids in Tripterygium wilfordii provides an effective new idea for obtaining these compounds. 2,3-Oxidosqualene cyclases (OSCs) are the key enzyme that catalyzes the formation of triterpene skeleton diversity. Based on the genome and transcriptome data of Tripterygium wilfordii, 16 OSC genes were identified and analyzed. Phylogenetic analysis showed that 16 TwOSC proteins could be mainly classified as four groups. They are β-amyrin synthase group, friedelin synthase group, multifunctional amyrin synthase and cycloartenol synthase group. TwOSC6 was successfully cloned. Functional characterization analysis revealed that TwOSC6 can catalyze the formation of α-amyrin and β-amyrin. This indicates that TwOSC6 is a multifunctional amyrin synthase. This provides new gene resources for the diversity of Tripterygium wilfordii triterpenoids, as well as new gene elements for biosynthesis triterpenoids.

Establishment and clinical application value of an automatic diagnosis platform for rectal cancer T-staging based on a deep neural network / 中华医学杂志(英文版)

BACKGROUND@#Colorectal cancer is harmful to the patient's life. The treatment of patients is determined by accurate preoperative staging. Magnetic resonance imaging (MRI) played an important role in the preoperative examination of patients with rectal cancer, and artificial intelligence (AI) in the learning of images made significant achievements in recent years. Introducing AI into MRI recognition, a stable platform for image recognition and judgment can be established in a short period. This study aimed to establish an automatic diagnostic platform for predicting preoperative T staging of rectal cancer through a deep neural network.@*METHODS@#A total of 183 rectal cancer patients' data were collected retrospectively as research objects. Faster region-based convolutional neural networks (Faster R-CNN) were used to build the platform. And the platform was evaluated according to the receiver operating characteristic (ROC) curve.@*RESULTS@#An automatic diagnosis platform for T staging of rectal cancer was established through the study of MRI. The areas under the ROC curve (AUC) were 0.99 in the horizontal plane, 0.97 in the sagittal plane, and 0.98 in the coronal plane. In the horizontal plane, the AUC of T1 stage was 1, AUC of T2 stage was 1, AUC of T3 stage was 1, AUC of T4 stage was 1. In the coronal plane, AUC of T1 stage was 0.96, AUC of T2 stage was 0.97, AUC of T3 stage was 0.97, AUC of T4 stage was 0.97. In the sagittal plane, AUC of T1 stage was 0.95, AUC of T2 stage was 0.99, AUC of T3 stage was 0.96, and AUC of T4 stage was 1.00.@*CONCLUSION@#Faster R-CNN AI might be an effective and objective method to build the platform for predicting rectal cancer T-staging.@*TRIAL REGISTRATION@#chictr.org.cn: ChiCTR1900023575; http://www.chictr.org.cn/showproj.aspx?proj=39665.

Ovarian cancer risk score predicts chemo-response and outcome in epithelial ovarian carcinoma patients / 부인종양

Objective@#Cytoreductive surgery followed by adjuvant chemotherapy is a standard frontline treatment for epithelial ovarian cancer (EOC). We aimed to develop an ovarian cancer risk score (OVRS) based on the expression of 10 ovarian-cancer-related genes to predict the chemoresistance, and outcomes of EOC patients. @*Methods@#We designed a case-control study with total 149 EOC women including 75 chemosensitives and 74 chemoresistants. Gene expression was measured using the quantitative real-time polymerase chain reaction. We tested for correlation between the OVRS and chemosensitivity or chemoresistance, disease-free survival (DFS), and overall survival (OS), and validated the OVRS by analyzing patients from the TCGA database. @*Results@#The chemosensitive group had lower OVRS than the chemoresistant group (5 vs.15, p≤0.001, Mann-Whitney U test). Patients with disease relapse (13 vs. 5, p60 months) of patients with OVRS ≥10 were significantly shorter than those of patients with OVRS <9). The high OVRS group also had significantly shorter median OS than the low OVRS group in 255 patients in the TCGA database (39 vs. 49 months, p=0.046). @*Conclusions@#Specific genes panel can be clinically applied in predicting the chemoresistance and outcome, and decision-making of epithelial ovarian cancer.

Correlation between serum uric acid level and impaired fasting glucose in adults / 中华健康管理学杂志

Objective:To investigate the correlation between different serum uric acid (SUA) levels and impaired fasting glucose (IFG) in adults.Methods:From March 2019 to February 2020, 5006 adults in Wuxi area of Taihu Sanatorium in Jiangsu Province were selected as subjects. Quintile method was divided into the following five groups: Q1: SUA<270 μmol/L, Q2: 270 μmol/L SUA 318 μmol/L or less, Q3: 319 μmol/L ≤SUA≤360 μmol/L, Q4: 361 μmol/L SUA 410 μmol/L or less, and Q5: SUA>410 μmol/L. Correlation was analyzed by logistic analysis, with IFG as the outcome index, five SUA groups as the observation index, and gender, age, body mass index (BMI), blood lipid, and blood pressure as confounding factors. Three logistic regression analysis models were constructed to explore the relationship between different SUA level groups and IFG risk, as well as the influence of BMI on the risk correlation between SUA and IFG.Results:The BMI, DBP, FPG, TC, TG, and LDL-C all increased with the increase in SUA level; however, HDL-C gradually decreased with the increase in SUA level (P<0.01). The SUA levels among the five groups were positively correlated with fasting blood glucose level in the IFG group ( r=0.589, P<0.001). After adjusting for age, sex, and BMI, SUA level was strongly associated with fasting glucose in the IFG group ( r=0.534, P<0.001). After further adjustment for blood lipid and blood pressure, the correlation persisted ( r=0.523, P<0.001). With Q1 as the control group, the calculated OR values of IFG risk were 1.199, 2.660, 2.784 and 3.629, respectively. After further adjustment for various confounding factors, the calculated OR values of each group were 1.130, 2.389, 2.350 and 2.895, respectively. The IFG risk in the group with SUA level in the corresponding Q2 and Q5 groups was 1.13 times and 2.90 times higher, respectively, than that in the normal group, indicating that with the increase in SUA level, the IFG risk in the population increased. With the increase in BMI and SUA levels after BMI stratification, the mean fasting glucose level increased ( P<0.001). Conclusion:The SUA level and IFG risk are closely related. Increased SUA level increases IFG risk, and SUA and IFG are associated with weight gain, which should be paid attention to.

Therapeutic effect of long-snake moxibustion combined with western medication on diarrhea type irritable bowel syndrome of spleen and kidney / 中国针灸

OBJECTIVE@#To compare the therapeutic effect between long-snake moxibustion combined with western medication and simple medication on diarrhea type irritable bowel syndrome (IBS-D) of spleen and kidney @*METHODS@#A total of 60 patients with IBS-D of spleen and kidney @*RESULTS@#Compared before treatment, the symptom scores of abdominal pain, defecation frequency, mucous stool and appetite reduction were decreased (@*CONCLUSION@#Long-snake moxibustion combined with western medication can effectively treat the IBS-D of spleen and kidney

Study on the Price and Affordability of Rare Disease Drug s in Chin a / 中国药房

OBJECTIVE：To evaluate the price and affordability of rare disease drugs in China and provide the suggestions for the improvement of rare disease drug affordability in order to provide reference for the relevant decision-making of government departments. METHODS ：According to the List of the First Batch of Rare Diseasesand Diagnosis and Treatment Guideline for Rare Diseases（2019 edition），rare disease drugs were selected. The median price ratio （MPR）was used to evaluate the drug price level ， and the ratio of the annual drug costs to the annual disposable income of urban or rural residents was used to evaluate the affordability，and the impact of price management policieson drug prices and affordability. RESULTS and CONCLUSIONS ：A total of 71 kinds of rare disease drugs were included ，and the median MPR of them was 0.83；among them ，the median MPR of the original drugs was 1.13，and the median MPR of the generic drugs was 0.37. The annual cost of 71 rare disease drugs was 0.001-178.43 times the average annual income of urban residents ，and 0.003-456.57 times the average annual income of rural residents. There were 21 and 28 drugs whose annual cost exceeded the annual income of urban and rural residents.After the implementation of national medical insurance negotiation or volume based procurement of 14 drugs，the median MPR of these drugs decreased from 1.71 to 0.46. For urban residents ，the number of unaffordable drugs had been reduced from 8 to 0；for rural residents，it had been reduced from 10 to 5. In summary ，the price level of orphan drugs in China was slightly lower than international reference price ，but the price level of original drugs was higher than the international reference price ，and the cost of some drugs far exceeded the residents ’ability to pay. It is suggested that the government should strengthen the price management of original drugs ，promote the substitution of high-quality generic drugs for original drugs ，and improve the payment system for high-value rare disease drugs.

Research progress on small molecule kinase inhibitors / 药学学报

Protein kinases are intimately involved in the pathogenesis of many diseases such as cancer, inflammation, and autoimmune and neurological diseases. Therefore, kinases have been widely studied as drug targets over the past three decades. As of April, 2020, the FDA had approved 59 small molecule kinase inhibitors (SMKIs) in the emerging field of targeted drug therapy. This paper focuses on the biochemistry and pharmacology of these 59 SMKIs and 121 SMKIs for which structures can be retrieved and that are now in phase Ⅱ and Ⅲ clinical trials. In addition, this paper also conducts a simple analysis of several popular targets and their inhibitors.

International Experience and Enlightenment of Medical Insurance Reimbursement for Multi-indication Drugs Based on Value-based Pricing / 中国药房

OBJECTIVE：To provide reference for improving medical insurance reimbursement for multi-indication drugs based on value-based pricing in China. METHODS：The theory and practice of value-based pricing for multi-indication drugs were sorted out，and the value standards and medical insurance reimbursement strategies based on value-based pricing in France，Germany，UK，Italy and Sweden were analyzed，so as to provide the suggestions for medical insurance reimbursement of multi-indication drugs in China. RESULTS & CONCLUSIONS：The realization of value-based pricing first needed to develop a value framework to define，measure and integrate value，and then established a model to convert the total value into price. The overall idea of value-based pricing for multi-indication drugs was consistent，but there were differences in the value standard. In the UK and Sweden， quality-adjusted life years （QALYs） and incremental cost-effectiveness ratios （ICERs） measured by pharmacoeconomicsare used as the value standard. France，Germany and Italy were more focused on the therapeutic value and clinical benefit improvement. As for medical insurance reimbursement strategies，France adopted single weighting method based on expected volume. Germany adopted combination weighting method based on value and volume. UK introduced the Patient Access Schemes and Italy introduced the Managed Entry reements，both based on the nominal reimbursement standard. Sweden adopted independent reimbursement for different indications by different brand names. It is suggested that China can explore the value-based pricing strategies of multi-indication drugs on the basis of the above international experiences，reference and use these variety of medical insurance reimbursement strategies comprehensively. Simultaneously，the information collection mechanism of patients and drug use should be improved to provide data support for the implementation of China’s value-based pricing and reimbursement strategies for multi-indication drugs.

Correlation Analysis between Chromaticity Value and Quality Index of Atractylodis chinensis Decoction Piece Powder Stir-fried with Bran and Its Processing Time Study / 中国药房

OBJECTIVE：To analysis the correlation between chrom aticity value and quality index of Atractylodis chinensis decoction piece powder stir-fired with bran ，and to determine its processing time. METHODS ：The processed samples of 16 batches of A. chinensis decoction piece stir-fired with bran （S0-S15，S0 is the raw product of A. chinensis ）were prepared ，and chromaticity values of all samples were determined ，such as lightness value （L*），yellow blue value （b*），red green value （a*）. UPLC fingerprint of sample were analyzed ，and the contents of extract and volatile oil were also determined. Pearson correlation was used to analyze the correlation between the chromaticity value and quality index （relative peak area of each chromatographic peak in UPLC fingerprint ，water-soluble extract content ，alcohol-soluble extract content and volatile oil content ）. Multivariate statistical analysis （principal component analysis ，cluster analysis ，partial least squares discriminant analysis ）was carried out with chromaticity value and quality index ，and the processing time of A. chinensis decoction piece stir-fired with bran was determined by grey correlation method. RESULTS ：In the process of bran frying ，with the extension of processing time ，L* and b* of decoction pieces powder decreased ，and a* increased first and then decreased ；relative areas of peak 1 and peak 2 increased first and then decreased，while relative areas of peak 3（5-hydroxymethyl furfural ）increased，and the areas of the other peaks decreased. The content of the extract did not change significantly with time ，and the content of the volatile oil decreased. The results of correlation analysis showed that the relative peak area of peak 2-27，alcohol-soluble extract content and volatile oil content had a certain correlation with the chromaticity value ，while the relative peak area of peak 1 and water-soluble extract content had no linear correlation with the chromaticity value. Results of multivariate statistical analysis showed that the samples were divided into mild （S0-S5），excessive （S12-S15），moderate （S6-processing time of 18-33 min）. The results of grey correlation method showed that the processing time of A. chinensis decoction piece stir-fired w ith bran should be controlled in the range of 18-24 min，and the optimal processing time was 18 min. CONCLUSIONS ：There is a correlation between chromaticity value of A. chinensis decoction piece powder stir-fired with bran and the relative peak area of 27 chromatographic peaks ，and content of extract and volatile oil. It is suggested that the processing time should be 18 min.

Effect of the active fraction of Huanglian-Jiedu Decoction on white matter injury in rats with cerebral ischemia by inhibiting NogoA/NgR expression / 国际中医中药杂志

Objective:To study the effect of Huanglian-Jiedu Decoction on the white matter lesion of rats with focal cerebral ischemia and to explore the regulative role of the active fraction of Huanglian-Jiedu Decoction on NogoA/NgR. Methods:Male SD rats were randomly divided into sham operation group, model group, total alkaloid group, total flavonoid group, and total iridoid group. Except for the sham operation group, the rats in the other groups were used to establish the middle cerebral artery occlusion rat model by the suture method. 2 hours after modeling, rats in the total alkaloid group were given intragastric administration with 44 mg/kg total alkaloids; rats in the total flavonoid group were given intragastric administration 50 mg/kg total flavonoids; rats in the total iridoid group were given intragastric administration 80 mg/kg total iridoids, the sham operation group and the model group were intragastrically given equal volume of normal saline, once a day, for 7 consecutive days. The pathological changes of rat white matter were observed by HE staining, the pathological changes of rat myelin sheath were observed by Luxol fast blue (LFB) staining, and the expression of Amyloid precursor protein (APP), NogoA, and NgR in the internal and external capsule areas of the brain was detected by immunohistochemical staining. Real-time fluorescence quantitative PCR was used to detect the expression of NogoA and NgR in the tissues surrounding the ischemic infarct.Results:Compared with the model group, the total alkaloid group, total flavonoid group, and total iridoid group had lower pathological damage scores in the internal and external capsule areas of rats ( P<0.05 or P<0.01), increased integral optical density value of LFB staining ( P<0.01), decreased expression of APP and NogoA; the expression of NgR in the internal and external capsules of rats in the total alkaloid group and the total iridoid group decreased ( P<0.05 or P<0.01), and the expression of NgR in the inner capsule of rats in the total flavonoid group decreased ( P<0.01); the expression of NogoA (1.20 ± 0.17, 1.55 ± 0.30, 1.19 ± 0.38 vs. 2.22 ± 0.58) and NgR (1.98 ± 0.55, 1.48 ± 0.31, 1.58 ± 0.27 vs. 3.36 ± 0.41) genes in the tissues around the infarct focus of rats in the total alkaloid group, total flavonoid group and total iridoid group decreased ( P<0.01). Conclusion:The present study investigates the therapeutic effects of Huanglian-Jiedu Decoction, promoting white matter repair by decreasing the overexpression of NogoA and NgR in an experimental animal model of stroke.

A dose-response meta-analysis on the relationship between daily tea intake and cardiovascular mortality based on the GRADE system / 中华心血管病杂志

Objective: To explore the relationship between daily tea intake and cardiovascular disease (CVD) mortality. Methods: PubMed, EMbase, The Cochrane, Chinese Biomedical Literature Database, CNKI, and Wanfang Database were searched to collect research on tea intake and CVD mortality. The search period was from the establishment of the database to June 2020. Two researchers independently screened and extracted literature. The risk of bias was evaluated in the included studies, a dose-response meta-analysis was conducted, sensitivity analysis and publication bias analysis of the research results, and quality evaluation of the included literature and GRADE classification of the evidence body were performed. Results: A total of 21 cohort or case-control studies were included, including 1 304 978 subjects. Among them, 38 222 deaths from CVD were reported. The quality scores of the included studies were all ≥ 6 points. The dose-response meta-analysis showed that for every additional cup of tea intake per day, the mortality rate of CVD decreased by about 3% (95%CI 0.95-0.98, P<0.05), and there was a non-linear dose-response relationship (P<0.05). Compared with people who do not drink tea, people who drink 1 to 8 cups of tea a day have 8% lower CVD mortality (RR=0.92, 95%CI 0.89-0.95), 13% (RR=0.87, 95 %CI 0.84-0.91), 15% (RR=0.85, 95%CI 0.82-0.89), 15% (RR=0.85, 95%CI 0.81-0.89), 16% (RR=0.84, 95%CI 0.80-0.89), 16% (RR=0.84, 95%CI 0.81-0.88), 16% (RR=0.84, 95%CI 0.81-0.87), 16% (RR=0.84, 95%CI 0.80-0.88), respectively. The results of traditional meta-analysis showed that compared with people who do not drink tea, people who drink more than 1 cup of tea a day are associated with 14% lower CVD mortality rate (RR=0.86, 95%CI 0.81-0.91, I2=73.2%, P<0.05). The results of subgroup analysis showed that compared with the corresponding people who did not drink tea, men who drank more than 1 cup of tea a day reduced the CVD mortality rate by 24%, women by 14%, European and American populations by 12%, and Asian populations by 15%. The population who consumed green tea decreased CVD mortality by 15%, and the population of non-smokers decreased CVD mortality by 20% (all P<0.05). The population who consumed black tea decreased CVD mortality by 8%, and the smoking population who consumed black tea decreased CVD mortality by 3%, and the difference was not statistically significant (all P>0.05). The results of the bias analysis showed that Begg=0.42 and Egger=0.62, indicating that the distribution on both sides of the funnel chart is symmetrical, suggesting that there is no publication bias. The results of sensitivity analysis showed that the effect size of the outcome index did not change significantly after excluding any article, indicating that the results are robust and credible. The GRADE evaluation showed that the evidence grades of the outcome indicators were all low grade. Conclusions: Daily tea consumption is related to reduced CVD mortality. It is therefore recommended to drink an appropriate amount of tea daily.