Intracranial activity of first-line immune checkpoint inhibitors combined with chemotherapy in advanced non-small cell lung cancer / 中华医学杂志(英文版)

BACKGROUND@#Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis.@*METHODS@#Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups.@*RESULTS@#Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs . 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs . 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed.@*CONCLUSION@#Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis.@*CLINICAL TRIAL REGISTRATION@#https://www.clinicaltrials.gov/ , OMESIA, NCT05129202.

Berberine targets the electron transport chain complex I and reveals the landscape of OXPHOS dependency in acute myeloid leukemia with IDH1 mutation / 中国天然药物

Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1mi.

lncRNA FTX silencing inhibits gastric cancer cell proliferation through the miR-22-3p/NLRP3 inflammasome pathway / 国际肿瘤学杂志

Objective:To investigate the regulatory effect of long non-coding RNA (lncRNA) FTX on gastric cancer cell proliferation through miR-22-3p/NOD-like receptor protein 3 (NLRP3) inflammasome pathway.Methods:The gastric cancer cell line NCI-N87 were divided into blank control group, si-FTX-NC group, si-FTX group, si-FTX+miR-22-3p inhibitor-NC group and si-FTX+miR-22-3p inhibitor group. Quantitative real-time fluorescent PCR was performed to analyze the expression levels of lncRNA FTX and miR-22-3p, clone formation assay was performed to analyze the proliferation ability of NCI-N87 cells, western blotting was performed to analyze the expressions of NLRP3 inflammasome pathway proteins, and dual-luciferase reporter assay was performed to analyze the targeting relationship between lncRNA FTX and miR-22-3p.Results:The relative expressions of lncRNA FTX in the blank control group, si-FTX-NC group, si-FTX group, si-FTX+miR-22-3p inhibitor-NC group and si-FTX+miR-22-3p inhibitor group were 1.03±0.09, 1.01±0.15, 0.42±0.08, 0.45±0.06 and 0.46±0.13 respectively, with a statistically significant difference ( F=52.19, P<0.001). The relative expressions of miR-22-3p were 1.04±0.12, 0.97±0.08, 2.26±0.15, 2.23±0.13 and 1.15±0.11 respectively, with a statistically significant difference ( F=178.53, P<0.001). Compared with the blank control group and si-FTX-NC group, the relative expressions of lncRNA FTX in the si-FTX group, si-FTX+miR-22-3p inhibitor-NC group and si-FTX+miR-22-3p inhibitor group decreased (all P<0.001). Compared with the blank control group, si-FTX-NC group and si-FTX+miR-22-3p inhibitor group, the relative expressions of miR-22-3p in the si-FTX group and si-FTX+miR-22-3p inhibitor-NC group increased (all P<0.001). The clones of the five groups were 115.50±7.25, 112.33±8.46, 54.83±5.17, 56.17±6.32 and 85.67±9.43, with a statistically significant difference ( F=91.67, P<0.001). The levels of NLRP3 protein in the five groups were 1.84±0.17, 1.86±0.12, 0.95±0.09, 0.97±0.11 and 1.28±0.19, with a statistically significant difference ( F=60.62, P<0.001). Compared with the blank control group and si-FTX-NC group, the number of clones and the level of NLRP3 protein of the si-FTX group, si-FTX+miR-22-3p inhibitor-NC group and si-FTX+miR-22-3p inhibitor group decreased (all P<0.05). Compared with the si-FTX+miR-22-3p inhibitor group, the number of clones and the level of NLRP3 protein in the si-FTX group and si-FTX+miR-22-3p inhibitor-NC group decreased (all P<0.05). The dual-luciferase reporter assay found that miR-22-3p was the target gene of lncRNA FTX. Conclusion:Silencing the expression of lncRNA FTX can inhibit the proliferation of gastric cancer cells, and the mechanism may be related to the regulation of lncRNA FTX on the miR-22-3p/NLRP3 inflammasome pathway.

Value of Intraplaque Neovascularization on Contrast-Enhanced Ultrasonography in Predicting Ischemic Stroke Recurrence in Patients With Carotid Atherosclerotic Plaque

Objective@#Patients with a history of ischemic stroke are at risk for a second ischemic stroke. This study aimed to investigate the relationship between carotid plaque enhancement on perfluorobutane microbubble contrast-enhanced ultrasonography (CEUS) and future recurrent stroke, and to determine whether plaque enhancement can contribute to risk assessment for recurrent stroke compared with the Essen Stroke Risk Score (ESRS). @*Materials and Methods@#This prospective study screened 151 patients with recent ischemic stroke and carotid atherosclerotic plaques at our hospital between August 2020 and December 2020. A total of 149 eligible patients underwent carotid CEUS, and 130 patients who were followed up for 15–27 months or until stroke recurrence were analyzed. Plaque enhancement on CEUS was investigated as a possible risk factor for stroke recurrence and as a possible adjunct to ESRS. @*Results@#During follow-up, 25 patients (19.2%) experienced recurrent stroke. Patients with plaque enhancement on CEUS had an increased risk of stroke recurrence events (22/73, 30.1%) compared to those without plaque enhancement (3/57, 5.3%), with an adjusted hazard ratio (HR) of 38.264 (95% confidence interval [CI]:14.975–97.767; P < 0.001) according to a multivariable Cox proportional hazards model analysis, indicating that the presence of carotid plaque enhancement was a significant independent predictor of recurrent stroke. When plaque enhancement was added to the ESRS, the HR for stroke recurrence in the high-risk group compared to that in the low-risk group (2.188; 95% CI, 0.025–3.388) was greater than that of the ESRS alone (1.706; 95% CI, 0.810–9.014). A net of 32.0% of the recurrence group was reclassified upward appropriately by the addition of plaque enhancement to the ESRS. @*Conclusion@#Carotid plaque enhancement was a significant and independent predictor of stroke recurrence in patients with ischemic stroke. Furthermore, the addition of plaque enhancement improved the risk stratification capability of the ESRS.

Effect of Circular RNA hsa_circ_0067582 on the Proliferation and Invasion Ability of Gastric Cancer Cells / 中国医学科学院学报

Objective To investigate the effects on cell proliferation and invasion of the circular RNA hsa_circ_0067582 in gastric cancer(GC). Methods After hsa_circ_0067582 overexpression (Oe-circ_0067582) plasmid was transfected into AGS and SGC-7901 cells,the cell viability,proliferation,invasion ability,and apoptosis were detected by CCK-8,colony formation and EdU assays,Transwell assay,and flow cytometry,respectively.Western blotting was employed to detect the expression levels of proteins related to the cell apoptosis and epithelial-mesenchymal transition(EMT).The effect of Oe-circ_0067582 on the growth of SGC-7901 cells in nude mice was observed.Bioinformatics tools were used to predict the binding target miRNA of hsa_circ_0067582,and the competing endogenous RNA(ceRNA)regulatory network was established.Finally,functional enrichment was performed to analyze the biological functions of the target genes of the predicted miRNA. Results Compared with the pLO-ciR(empty plasmid)group,the Oe-circ_0067582 group in AGS and SGC-7901 cells attenuated the cell viability(t=7.883,P=0.001;t=5.679,P=0.005),proliferation(t=6.709,P=0.003;t=5.857,P=0.003),and invasion ability(t=7.782,P=0.002;t=6.342,P=0.003)and induced cell apoptosis(t=7.225,P=0.002;t=11.509,P=0.001).Western blotting showed that the Oe-circ_0067582 group in AGS and SGC-7901 cells up-regulated the protein levels of cysteinyl aspartate specific proteinase (Caspase) 3(t=6.863,P=0.002;t=7.024,P=0.001),Caspase 7(t=3.295,P=0.04;t=6.008,P=0.004),Caspase 9(t=4.408,P=0.012;t=6.278,P=0.004),and E-cadherin(t=12.453,P=0.002;t=10.867,P=0.001),while down-regulated those of Vimentin(t=7.242,P=0.002;t=5.694,P=0.004)and N-cadherin(t=6.480,P=0.003;t=7.446,P=0.001).Furthermore,Oe-circ_0067582 significantly inhibited the growth of tumor in the SGC-7901 tumor-bearing nude mice(t=3.526,P=0.017).The prediction based on TargetScan and miRnada suggested that hsa_circ_0067582 can competitively bind to hsa-miR-181b-3p,hsa-miR-337-3p,hsa-miR-421,and hsa-miR-548d-3p.The functional enrichment indicated that the target genes of miRNA were involved in multiple cancer-related biological processes including negative regulation of apoptotic process,gene expression,transcriptional misregulation in cancer,transforming growth factor-β,and p53 signaling pathways. Conclusion Oe-circ_0067582 can inhibit the proliferation and attenuate EMT process to reduce the invasion ability of AGS and SGC-7901 cells,which provides a new target for the treatment of GC.

Research on Dual-channel Pricing Strategy of Pharmaceutical Retailing Considering Medical Insurance Payment Policy / 中国药房

OBJECTIVE：To provide reference for the drug retailers when making dual-channel pricing decisions in China. METHODS：Based on the analysis of the existing literature and the characteristics of drug supply chain ，taking the dual-channel drug retailers as the research object ，the effects of medical insurance payment policy ，consumers’risk aversion factor and inconvenience cost on consumers ’decision-making behavior were considered ，and dual-channel pricing strategy model for drug retailers was constructed. The reverse induction method was adopted to analyze and solve the model ，obtain the optimal pricing and optimal profit function of the drug retailer. The numerical simulation was adopted to simulate and analyze the effects of consumer medical insurance payment utility ，risk aversion factor and inconvenience cost on drug retailer dual-channel pricing and profits. RESULTS：When the utility of medical insurance payment increased ，the pricing of drugstores and the total profit of dual-channel of drug retailers would increase ；while consumers ’risk aversion factor and inconvenience cost showed a U-shaped trend with retailer ’s dual-channel total profits. In addition ，compared with existing e-commerce platforms ，retailers could make more profits by building their own e-commerce platforms. CONCLUSIONS ：Medical insurance payment policy has a great impact on the profits of dual-channel drug retailers. Drug retailers should continue to pay attention to the trend of relevant national policies and ensure their own profits by adjusting pricing in time. When medical insurance payment utility is in low level ，dual-channel drug retailers can ensure market demand by reducing the retail price of drugstores ，and should use flexible sales strategies to attract consumers. For consumers’risk aversion and inconvenience cost ，drug retailers can adopt strategies such as providing distribution services for consumers with high inconvenience cost.

Visual Analysis of the External Characteristics and Research Hotspots of Literatures in International Forensic Science / 法医学杂志

Objective To analyze the forensic science-related literature included in the Web of Science database in the recent decade through bibliometric methods, to provide reference for relevant research. Methods Literatures were searched in 3 ways： Subject search, Journal search and Institution search. The annual distribution, national （regional） distribution, institution distribution, journal distribution and the research hotspots of the related literatures were analyzed through Thomson Data Analyzer （TDA）, Ucinet, VOSviewer, and so on. Results A total of 49 469 related literatures were included in the recent decade. The number of literatures continued to climb year by year. The top 15 countries （regions） accounted for 78.52% of the total number of published literatures, and China ranked 5th, but ranked 12th in terms of the proportion of high-cited papers; Netherlands, Switzerland, Australia, etc. had high comprehensive influence. The number of countries （regions） that cooperated with China were 129, including the United States, the United Kingdom and Germany. The Institute of Forensic Science of Saint Mary's University, University of Sydney and Netherlands Forensic Institute had high comprehensive influence, and the related literatures were published on 6 357 journals. According to high-frequency co-occurrence network and high-cited papers, brain injury, health policy, assessment scales and models and medical imaging were selected as research hotspots. Conclusion The total number of literatures in forensic science included in international SCI increased significantly, and the influence of China's achievements needs to be greatly enhanced; the research institutions were scattered, and China's research power needs to be continuously condensed; the research hotspots in international fields are extensive, and the international participation of China in top level research needs to be strengthened.

Relationship between the ideal cardiovascular health behaviors and factors and newonset heart failure / 中华心血管病杂志

Objective: To explore the relationship between the ideal cardiovascular health behaviors and factors and newonset heart failure. Methods: It was a prospective cohort study. People who attended the 2006-2007 physical examination of Kailuan Group Company and with complete data of cardiovascular behaviors and related factors were eligible for this study. A total of 95 167 participants who were free of valvular heart diseases, congenital heart diseases and a prior history of heart failure were included. Basic cardiovascular health score (CHS) of each participant was calculated. Participants were divided into 3 groups according to CHS. Group 1:CHS<8 (n=26 640), Group 2:8≤CHS<10 (n=35 230), Group3:CHS≥10 (n=33 297). The general clinical data and laboratory test results were collected. The outcome was defined as the first occurrence of heart failure at the end of followup(December 31, 2016). Cox regression model was used to determine the association between baseline CHS and the risk of newonset heart failure. Results: After a median followup of 10.3 years, the incidence of newonset heart failure in the group of CHS<8,8≤CHS<10,CHS≥10 were 2.7%(729/26 640), 1.8%(651/35 230) and 1.1%(360/33 297),respectively. After adjustment for age, sex, history of myocardial infarction, history of atrial fibrillation, income, alcohol consumption, education and the use of antihypertensive, cholesterol-lowering, glucose-lowering medications, compared with the group of CHS<8, the Cox regression model showed that HRs of the group of 8≤CHS<10 and CHS≥10 were 0.68 (95%CI 0.61-0.75), 0.49 (95%CI 0.43-0.55), respectively. Cox regression analysis after removing each single cardiovascular behavior or factor showed that the HR value range ability was as follows:systolic blood pressure(HR=0.78,95%CI 0.74-0.82), body mass index(HR=0.78,95%CI 0.74-0.82), fasting blood glucose (HR=0.77,95%CI 0.73-0.81), total cholesterol(HR=0.76,95%CI 0.72-0.80), physical exercise(HR=0.72,95%CI 0.69-0.76), smoking(HR=0.75,95%CI 0.71-0.79) and salt intake(HR=0.73,95%CI 0.69-0.77). Conclusion: CHS is negatively associated with the risk of newonset heart failure, and there is a dose-response relationship between the two indexes.

Analysis of Retail Pharmacy Layout in Liaoning Province Based on the Government Perspective / 中国药房

OBJECTIVE：To investigate rationality of existing retail pharmacy layout in Liaoning province ，and to discuss the rationalization of retail pharmacy layout from the perspective of the government. METHODS ：By introducing the concept of coverage radius ，comprehensive use of population ，area，number of retail pharmacies ，average number of people covered by each retail pharmacy ，the difference between the number of pharmacies （calculated according to the coverage radius and area ）and the number of existing pharmacies ，the shortest distance between two retail pharmacies as indicators ，the overall retail pharmacies layout in 14 cities of Liaoning province and the specific layout of retail pharmacies in Shenyang were analyzed to put forward the idea of optimizing the retail pharmacies layout. RESULTS & CONCLUSIONS ：The correlation of the number of existing retail pharmacies in Liaoning province with the population and land area to a certain extent showed no obvious law ，with some degree randomness. The average number of people covered by each pharmacy is 1 917-4 157 in each city ；the average number of people covered by retail pharmacies in the remaining 10 cities like Yingkou is lower than the provincial average. The average number of people covered in Chaoyang and other 3 cities is higher ，with great development space. The number of existing retail pharmacies in 8 districts and counties such as Tiexi district do not meet the actual needs of consumers （the number of existing pharmacies is 2- 3 921 less than the number of due pharmacies ），while the number of existing retail pharmacies in 3 districts such as Shenhe district far exceeds the required number （the number of existing pharmacies is 142-248 more than the number of due pharmacies ）. There is a problem of too small spacing between adjacent retail pharmacies （the minimum distance is less than 500 m）. The distribution of retail pharmacies in Liaoning province is unbalanced ，and there is insufficient demand in some areas. When optimizing of retail pharmacies layout ，the government should establish a double objective evaluation system ，which is fair （measured by the maximum distance between the uncovered demand area and the nearest retail pharmacies ）and efficient （measured by the sum of the number of retail drugstores needed for the existing layout and the number of new retail drugstores ）. It is also necessary to analyze and construct a retail pharmacies location model which is suitable for China ’s national conditions ，and consider the actual conditions of the parameters of the actual constraints and objective constraints ，so as to realize the overall optimization of retail drugstores .

Application of percutaneous pie-crusting deep medial collateral ligament release for posterior horn surgery of medial meniscus / 中国骨伤

OBJECTIVE@#To explore clinical and radiographic effects of percutaneous pie-crusting deep medial collateral ligament release in patients with posterior horn tear of medial meniscus combined with tight medial compartment.@*METHODS@#From January 2012 to December 2016, 35 patients with medial meniscus posterior horn injury were treated with percutaneous pie crusting deep medial collateral ligament release technique, including 21 males and 14 females, aged from 21 to 55 years old with an average of (39.1±6.5) years old. Degree of meniscus extrusion were recorded before and 24 months after operation. The knee valgus stress test was performed to evaluate stability of medial collateral ligament, and compared difference between healthy and affected side. Lysholm and IKDC functional scores were compared before and 24 months after operation.@*RESULTS@#All patients were followed up from 27 to 60 months with an average of (36.7±6.8) months. All patients were underwent operation, the wound healed well without complications. Operative time ranged from 0.5 to 1.2 h with an average of (0.8±0.4) h. Nineteen patients were performed partial meniscectomy, 16 patients were performed repair suture. Convex of meniscus before operation was (1.5±0.7) mm, and (1.7±0.4) mm after operation;had no statistical difference(@*CONCLUSION@#For patients with medial meniscus tear of posterior horn combined with tight medial compartment, percutaneous pie-crusting deep medial collateralligament release could improve medial compartment space, and Knee valgus instability and meniscus extrusion are not affected.

Study on Green Innovation in Pharmaceutical Enterprises Based on Grounded Theory / 中国药房

OBJECTIVE：To study the influential factors for green innovation in pharmaceutical enterprises based on grounded theory so as to provide reference for pharmaceutical enterprises to enhance their green innovation ability and the government to issue relevant green policies. METHODS ：The grounded theory research methods were used to select enterprise samples and follow-up research. Firstly ，56 staffs from 22 sample enterprises （all were pharmaceutical companies ）were interviewed in depth one-on-one and face-to-face on issues related to the influential factors for green innovation. Then ，open coding ，spindle coding and selective coding were carried out on the conversation record data ，and conduct theoretical saturation testing was conducted. Finally ， the influential factor model of green innovation in pharmaceutical enterprises was constructed ，and its main influential factors were analyzed. RESULTS & CONCLUSIONS ：The government demand ，social demand ，industry demand ，green innovation ability ， environmental awareness of leaders and overall vision of leaders have significant influence on the green innovation of pharmaceutical enterprises. Among them ，leadership decision （including leaders ’environmental awareness and leadership pattern ） is the internal decisive factor ，green innovation ability （including green innovation investment capacity ，green innovation research and development capacity ，green innovation transformation capacity and green innovation production capacity ）is the internal driving factor ，social system （including government needs ，social needs and industry needs ）is the external factor ；they are the main factors affecting the green innovation of pharmaceutical enterprises ，and they all have a positive effect on the green innovation of pharmaceutical companies.

Analysis on sensory processing characteristics of mental health problems in preschoolers / 中国学校卫生

Objective@#To analyze the sensory processing characteristics among preschoolers with mental health problems in Nanshan District, Shenzhen.@*Methods@#Random cluster sampling was used to select kindergartens for psychological screening from March to June 2018. The Strengths and Difficulties Questionnaire (SDQ) and the Simplified Sensory Questionnaire (SSP) were used to evaluate 6 365 preschool children.@*Results@#A total of 15.15% preschoolers were detected with abnormal results. The SSP scores of preschoolers with emotional symptoms/conduct problems/prosocial behaviors were lower than normal preschoolers’(P<0.01). Among the preschoolers with hyperactivity-inattention, taste/smell sensitivity (F=12.45)/underresponsive/seeks sensation(F=102.44), auditory filtering(F=93.51), low energy/weak(F=13.33), visual/auditory sensitivity (F=4.32) scores were lower than normal preschoolers’(P<0.05), the scores of tactile sensitivity movement sensitivity were no statistical difference with normal preschoolers’. Among the preschoolers with peer problem, taste/smell sensitivity(F=5.86), tactile sensitivity(F=6.05), movement sensitivity(F=4.70), auditory filtering(F=17.32), low energy/weak (F=9.56), visual/auditory sensitivity (F=4.16) scores were lower than normal preschoolers’ (P<0.05), and the scores of under-esponsive/seeks sensation were no statistical difference with normal pre-schoolers’. Prosocial behavior and tactile (r=0.30), under-responsive/seeks sensation(r=0.37), auditory filtering(r=0.37), low energy/weak (r=0.31) were positive associated(P<0.01). Emotional symptoms were negatively associated with lack of energy/weakness(r=-0.33, P<0.01).@*Conclusion@#Mental health problems are related to sensory processing ability in preschoolers. Preschoolers with mental health problems have weak sensory processing ability. Clinicians and occupational therapists should pay attention to evaluation and intervention of sensory processing ability in preschoolers with mental health problems.

Impact of change of ideal cardiovascular behavior and related factors on healthy vascular aging / 中华心血管病杂志

Objective: To investigate the impact of change of ideal cardiovascular behavior and related factors on healthy vascular aging(HVA). Methods: This study was a multi-center cross-sectional survey. Six thousand three hundred and sixteen participants who underwent at least 2 healthy examinations from 2006 to 2015 at 11 hospitals, including Kailuan Hospital and so on, and examined brachial-ankle pulse wave velocity (baPWV) during 2010 and 2016, with available information about cardiovascular behavior and factors were included. The cardiovascular health score (CHS) was calculated. Basic CHS was collected from the first examination. The second CHS derived from the healthy examination in the same year of baPWV examination. Change of cardiovascular health score (ΔCHS) was calculated. Participants were defined into 5 groups according to ΔCHS, namely ΔCHS≤-2 (n=2 166), ΔCHS=-1 (n=1 284), ΔCHS=0 (n=1 187), ΔCHS=1 (n=860), and ΔCHS≥2 (n=819). Participants' characteristics, value of baPWV and proportion of HVA were compared among different groups. Multiple logistic regression analysis was used to investigate the association between ΔCHS and HVA. The ΔCHS was recalculated and included in multiple logistic regression analysis model again after each component of the cardiovascular health metrics was removed separately in order to investigate effects of removal factors on HVA by observing changes in effect values. Results: The percentage of the participants with HVA in the group of ΔCHS≤-2, ΔCHS=-1, ΔCHS=0, ΔCHS=1 and ΔCHS≥2 were 23.3%(505/2 166), 27.8%(357/1 284), 28.7%(341/1 187),31.9%(274/860) and 33.9%(278/819), respectively. After adjustment for age, sex, income, education, alcohol consumption and the basic CHS, a significant positive association between ΔCHS and proportion of participants with HVA was observed (OR=1.50, 95%CI 1.44-1.56). Multiple regression analysis after removing each single cardiovascular behavior or factor showed that the OR value decreased as follow systolic blood pressure (OR=1.04, 95%CI 1.00-1.09), fasting blood glucose (OR=1.14, 95%CI 1.09-1.18), physical exercise (OR=1.16, 95%CI 1.11-1.21), salt intake (OR=1.17, 95%CI 1.12-1.22), body mass index (OR=1.18, 95%CI 1.13-1.23), smoking(OR=1.18, 95%CI 1.13-1.23) and total cholesterol (OR=1.20, 95%CI 1.16-1.24). Conclusion: The improvement of every ideal cardiovascular behavior and factor is associated with the increase of the proportion of HVA population.

Impact of change of ideal cardiovascular behavior and related factors on healthy vascular aging / 中华心血管病杂志

Objective@#To investigate the impact of change of ideal cardiovascular behavior and related factors on healthy vascular aging(HVA).@*Methods@#This study was a multi-center cross-sectional survey. Six thousand three hundred and sixteen participants who underwent at least 2 healthy examinations from 2006 to 2015 at 11 hospitals, including Kailuan Hospital and so on, and examined brachial-ankle pulse wave velocity (baPWV) during 2010 and 2016, with available information about cardiovascular behavior and factors were included. The cardiovascular health score (CHS) was calculated. Basic CHS was collected from the first examination. The second CHS derived from the healthy examination in the same year of baPWV examination. Change of cardiovascular health score (ΔCHS) was calculated. Participants were defined into 5 groups according to ΔCHS, namely ΔCHS≤-2 (n=2 166), ΔCHS=-1 (n=1 284), ΔCHS=0 (n=1 187), ΔCHS=1 (n=860), and ΔCHS≥2 (n=819). Participants′ characteristics, value of baPWV and proportion of HVA were compared among different groups. Multiple logistic regression analysis was used to investigate the association between ΔCHS and HVA. The ΔCHS was recalculated and included in multiple logistic regression analysis model again after each component of the cardiovascular health metrics was removed separately in order to investigate effects of removal factors on HVA by observing changes in effect values.@*Results@#The percentage of the participants with HVA in the group of ΔCHS≤-2, ΔCHS=-1, ΔCHS=0, ΔCHS=1 and ΔCHS≥2 were 23.3%(505/2 166), 27.8%(357/1 284), 28.7%(341/1 187),31.9%(274/860) and 33.9%(278/819), respectively. After adjustment for age, sex, income, education, alcohol consumption and the basic CHS, a significant positive association between ΔCHS and proportion of participants with HVA was observed (OR=1.50, 95%CI 1.44-1.56). Multiple regression analysis after removing each single cardiovascular behavior or factor showed that the OR value decreased as follow systolic blood pressure (OR=1.04, 95%CI 1.00-1.09), fasting blood glucose (OR=1.14, 95%CI 1.09-1.18), physical exercise (OR=1.16, 95%CI 1.11-1.21), salt intake (OR=1.17, 95%CI 1.12-1.22), body mass index (OR=1.18, 95%CI 1.13-1.23), smoking(OR=1.18, 95%CI 1.13-1.23) and total cholesterol (OR=1.20, 95%CI 1.16-1.24).@*Conclusion@#The improvement of every ideal cardiovascular behavior and factor is associated with the increase of the proportion of HVA population.

Research on the Development Path of Building a World-class Pharmacy Discipline / 中国药学杂志

OBJECTIVE: To analyze the current status of China's pharmacy discipline rankings, and compare the development gap between China's pharmacy disciplines and world-class pharmacy disciplines to explores the development path of building a world-class pharmacy discipline. METHODSE: Website research, literature research, and comparative analysis were adopted. RESULTS AND CONCLUSION: The ranking status of pharmacy disciplines in China is compared and analyzed, and from the three aspects of the index system, international influence, and innovative talents training, the development path of building world-class pharmacy discipline in China is proposed.

A cohort study on the association between resting heart rate and the risk of new-onset heart failure / 中华心血管病杂志

Objective: To prospectively explore the relationship between resting heart rate (RHR) and risk of new-onset heart failure. Methods: It was a prospective cohort study. People who attended the physical examination of Kailuan Group Company in 2006 and with complete electrocardiography (ECG) recordings were eligible for this study. A total of 88 879 participants aged 18 years old or more who were free of arrhythmia, a prior history of heart failure and were not treated with β-blocker were included. Participants were divided into 5 groups according to the quintiles of RHR at baseline (Q(1) group, 40-60 beats/minutes (n=18 168) ; Q(2) group, 67-70 beats/minutes (n=18 970) ; Q(3) group, 71-74 beats/minutes (n=13 583) ; Q(4) group, 75-80 beats/minutes (n=22 739) ; and Q(5) group,>80 beats/minutes (n=15 419) ) .The general clinical data and laboratory test results were collected. The outcome was the first occurrence of heart failure at the end of follow-up (December 31, 2016) .We used Cox regression model to examine the association between RHR and the risk of new-onset heart failure. Hazard ratio (HR) with 95% confidence intervals (CI) were calculated using Cox regression modeling. Results: Among the included patients 68 411 participants were male, mean age was (51.0±12.3) years old, and RHR was (74±10) beats/minutes. Statistically significant differences among the RHR quintiles were found for the following variables: age, gender, systolic blood pressure, diastolic blood pressure, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood glucose, body mass index, the level of high-sensitivity C-reactive protein, education status, physical activity, smoking status, drinking status, history of diabetes, history of hypertension and history of use antihypertensive drugs (all P<0.01) . Higher RHR was linked with higher prevalence of diabetes, hypertension history, and higher systolic blood pressure, diastolic blood pressure and FBG levels (all P<0.01). After a mean follow-up of 9.5 years, the incidence of new-onset heart failure in Q(1), Q(2), Q(3), Q(4) and Q(5) groups was 1.60%(290/18 168), 1.36%(258/18 970), 1.80%(245/13 583), 1.76%(400/22 739) and 2.35%(362/15 419),respectively (P<0.01) . The person-year incidence of heart failure in Q(1), Q(2), Q(3), Q(4) and Q(5) groups was 1.7, 1.5, 1.9, 1.9 and 2.6 per 1 000 person-years respectively. Compared with the Q(2) group, multivariate analysis with adjustment for major traditional cardiovascular risk factors showed that HRs of Q(3),Q(4),and Q(5) group were 1.23 (95%CI 1.03-1.48, P<0.05) , 1.19 (95%CI 1.01-1.41, P<0.05) , 1.39 (95%CI 1.18-1.65, P<0.01) , respectively. In the absence of hypertension, diabetes, smoking and acute myocardial infarction, the Cox regression model showed that compared with Q(2) group, the HR of new-onset heart failure in Q(5) group was 1.58 (95%CI 1.02-2.45, P<0.05) . Conclusion: Increased RHR is associated with increased risk of new-onset heart failure in this cohort.

Subsidy Strategy of Generic Drug Conformance Assessment Based on Patient Heterogeneity / 中国药房

OBJECTIVE： To consider the heterogeneity of patients’ acceptance of generic drugs， to establish a game decision-making model between pharmaceutical enterprises and the government， and to provide decision-making basis for the government to formulate subsidy policies for the generic drug conformance assessment. METHODS： A two-stage game model was established on the basis of patient heterogeneity under three subsidy strategies： the government does not subsidize， subsidize generic drug companies and subsidize patients. Effects of patient heterogeneity on the decision-making of pharmaceutical enterprises and the government were compared and analyzed under three subsidy strategies. RESULTS： With the increase of patients’ recognition of generic drugs， the market demand for generic drugs is also increasing. The relationship between the market price of generic drugs and government subsidies was negatively correlated when subsidies were given to generic pharmaceutical enterprises， and positively correlated when subsidies were given to consumers. CONCLUSIONS： Government subsidies can increase consumer surplus and social welfare， and the social benefits of government subsidies for patients and generic pharmaceutical enterprises are the same. On the premise of achieving the same social welfare， the government can adopt the strategy of subsidizing generic pharmaceutical enterprises to reduce government expenditure. The form of subsidizing patients is adopted to encourage the generic pharmaceutical enterprises to carry out the generic consistency evaluation.

Establishment of Rational Drug Use Evaluation Model Based on 360-degree Feedback Evaluation Method and Hesitant Fuzzy Sets Theory / 中国药房

OBJECTIVE： To establish a comprehensive and multi-angle evaluation model for rational drug use in medical institutions， and to provide support for rational drug use in medical institutions. METHODS： Referring to the phenomenon of irrational drug use and its influential factors in medical institutions， rational drug use evaluation indicator system， which contained 3 evaluation subjects， 6 first-level indicators and 15 second-level indicators， was established on the basis of 360-degree Feedback Method， with hospitals at the same level， superior regulation department and patient as subjects of multi-angle evaluation. At the same time， the linguistic information of vague and uncertain evaluation given by the evaluation subject was comprehensively quantified by Hesitant Fuzzy Sets Theory. The total evaluation score of rational drug use in the evaluated medical institutions was calculated by using the score function formula of hesitant fuzzy number； the level of rational drug use in medical institutions was determined according to the score （the higher the total score， the higher the comprehensive level of rational drug use）. RESULTS： An all-round and multi-angle evaluation model of rational drug use in medical institutions was established. According to the evaluation index system based on 360-degree feedback evaluation method， the evaluation subject and weight of evaluation index were determined， the grade of evaluation index was divided， the hesitant fuzzy numbers of each index were gathered， and the first-level index was weighted. Finally， the total evaluation score of rational drug use in medical institutions was calculated； the examples were set to prove the feasibility of the model. CONCLUSIONS： The established evaluation model for rational drug use in medical institutions based on 360-degree Feedback Method and Hesitant Fuzzy Sets Theory can comprehensively and effectively evaluate the rational drug use in medical institutions， and contribute to standardizing and improving clinical drug use behavior in medical institutions.

Identification of active components in Longxue Tongluo Capsules against ischemic brain injury based on component-activity relationship / 中国中药杂志

Ten fractions(A-J) were prepared by separation of Longxue Tongluo Capsules(LTC) by using silica gel column chromatography and orthogonal experimental design,showing similar chemical profiles with different abundances of peaks.These ten samples were assessed with UHPLC-QE OrbitrapHRMS for 97 common peaks.For the pharmacological activity experiment,three kinds of in vitro cell models including lipopolysaccharide(LPS)-induced BV-2 microglial cells NO release model,oxygen-glucose deprivation/reoxygenation(OGD/R)-treated HUVEC vascular endothelial cells injury model,and OGD/R-treated PC-12 nerve cells injury model were employed to evaluated the bioactivity of each fraction.Based on the contribution of each identified component,grey relation analysis and partial least squares(PLS) analysis were performed to establish component-activity relationship of LTC,identify the potential active components.After that,validation of the potential active components in LTC was carried out by using the same models.The results indicated that 4 phenolic compounds including 7,4'-dihydroxyhomoisoflavanone,loureirin C,4,4'-dihydroxy-2,6-dimethoxydihydrochalcone,and homoisosocotrin-4'-ol,might be the active components for anti-neuroinflammation effect;five phenolic compounds such as 3,5,7,4'-tetrahydroxyhomoisoflavanone,loureirin D,7,4'-dihydroxyhomoisoflavane,and 5,7-dihydroxy-4'-methoxy-8-methyflavane,might have positive effects on the vascular endothelial injury;three phenolic compounds including 5,7,4'-trihydroxyflavanone,7,4'-dihydroxy-5-methoxyhomoisoflavane,and loureirin D,might be the active components in LTC against neuronal injury.

LC-MS guided isolation of two anti-inflammatory cyclic dihydrochalcane trimers from Chinese dragon's blood / 中国中药杂志

As an important integral part of traditional Chinese medicine chemical biology( TCMCB),it is of great importance to rapid isolate,and reliably identify the chemical components in herbal medicines. Phytochemical studies on the anti-inflammatory active part of Chinese dragon's blood,the red resin of Dracaena cochinchinensis,resulted in the isolation of two compounds,nordracophane( 1) and dracophane( 2),using LC-MS and chromatographic techniques( Silica gel,ODS and preparative HPLC). The structures,cyclic dihydrochalcane trimers,were elucidated on the basis of 1 D and 2 D NMR,MS,IR and UV spectral analysis. Compound 1 is a new compound,and 2 is isolated from D. cochinchinensis for the first time. Both compounds exhibited significant inhibition of nitric oxide production in lipopolysaccharides( LPS)-stimulated RAW264. 7 cells with IC50 values of( 14. 9±4. 50) and( 9. 0±0. 7) μmol·L-1.