Background: Cardiovascular disease is the leading cause of death worldwide and a major barrier to sustainable human development. The objective of this study was to evaluate the global, sex, age, region, and country-related cardiovascular disease (CVD) burden, as well as the trends, risk factors, and implications for the prevention of CVD.Methods: Detailed information from 1990 to 2017, including global, regional, and national rates of CVD, and 11 categories of mortality and disability-adjusted life years (DALYs) were collected from the Global Burden of Disease Study 2017. The time-dependent change in the trends of CVD burdens was evaluated by annual percentage change.Results: More than 17 million people died from CVD in 2017, which was approximately two times as many as cancer, and increased nearly 50% compared with 1990. Ischemic heart disease and stroke accounted for 85% of the total age-standardized death rate (ASDR) of CVD. The ASDR and age-standardized DALYs rate (ASYR) of CVD were 1.5 times greater in men compared with women. People over the age of 50 were especially at risk for developing CVD, with the number of cases and deaths in this age group accounting for more than 90% of all age groups. CVD mortality was related to regional economic development and the social demographic index. In regions with a high economic income or socio-demographic index, there was a greater decline in the ASDR of CVD. The ASDR of CVD in high SDI regions decreased more than 50% from 1990 to 2017. Tobacco use, diets low in whole grains, diets high in sodium, and high systolic blood pressure were the important risk factors related to CVD mortality.Conclusions: CVD remains a major cause of death and chronic disability in all regions of the world. Ischemic heart disease and stroke account for the majority of deaths related to CVD. Although the mortality rate for CVD has declined in recent years from a global perspective, the results of CVD data in 2017 suggest that the mortality and DALYs of CVD varied in different ages, sexes, and countries/regions around the world. Therefore, it is necessary to elucidate the specific characteristics of global CVD burden and establish more effective and targeted prevention strategies.

Background and aims Cancer will soon become the leading cause of death in every country in the twenty-first century. This study aimed to analyze the mortality and morbidity of 29 types of cancer in 204 countries or regions from 1990 to 2019 to guide global cancer prevention and control. Methods Detailed information for 29 cancer groups was collected from the Global Burden of Disease Study in 2019. The age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) of the 29 cancer groups were calculated based on sex, age, region, and country. In addition, separate analyses were performed for major cancer types. Results In 2019, more than 10 million people died from cancer, which was approximately twice the number in 1990. Tracheal, bronchus, and lung (TBL) cancers collectively showed the highest death rate, and the ASDR of pancreatic cancer increased by 24%, which was cancer with the highest case fatality rate (CFR). The global cancer ASIR showed an increasing trend, with testicular cancer, thyroid cancer, and malignant skin melanoma showing a significant increase. The ASDR and ASIR of cancer in males were about 1.5 times higher than that in females. Individuals over 50 years had the highest risk of developing cancer, with incidences and deaths in this age group accounting for more than 85% of cancers in all age groups. Asia has the heaviest cancer burden due to its high population density, with esophageal cancer in this region accounting for 53% of the total fatalities related to this type of cancer in the world. In addition, the mortality and morbidity of most cancers increased with the increase in the development or socio-demographic index (SDI) in the SDI regions based on the World Bank's Human Development Index (HDI), with cancer characteristics varying in the different countries globally. Conclusions The global cancer burden continues to increase, with substantial mortality and morbidity differences among the different regions, ages, countries, gender, and cancer types. Effective and locally tailored cancer prevention and control measures are essential in reducing the global cancer burden in the future.

The research and development (R&D) of new drugs indicates scientific progress and economic development. However, little is known regarding ongoing or recent clinical trials in China. We analyzed data from clinical trials published before December 31, 2019, and found that the annual registration numbers are increasing annually in the country. Based on clinical indications, most tested drugs target cancers, nervous system, infections, and the cardiovascular system. Furthermore, clinical trials are mostly concentrated in Beijing, Shanghai, and Jiangsu, and conducted by large pharmaceutical companies, with multiple trials for several generic drugs. Going forward, it will be necessary to promote R&D in China of clinically relevant innovative drugs, drug delivery systems, and novel traditional Chinese medicine (TCM) and biological products, as well as to have a balanced distribution of clinical trials to sustainably meet public health needs.

The research and development (R&D) of new drugs indicates scientific progress and economic development. However, little is known regarding ongoing or recent clinical trials in China. We analyzed data from clinical trials published before December 31, 2019, and found that the annual registration numbers are increasing annually in the country. Based on clinical indications, most tested drugs target cancers, nervous system, infections, and the cardiovascular system. Furthermore, clinical trials are mostly concentrated in Beijing, Shanghai, and Jiangsu, and conducted by large pharmaceutical companies, with multiple trials for several generic drugs. Going forward, it will be necessary to promote R&D in China of clinically relevant innovative drugs, drug delivery systems, and novel traditional Chinese medicine (TCM) and biological products, as well as to have a balanced distribution of clinical trials to sustainably meet public health needs.

BACKGROUND AND AIMS:Cancer has become the second most serious disease threatening human health, followed by cardiovascular diseases. This study aimed to quantitatively estimate the mortality, morbidity, and analyze the trends of 29 cancer groups in 195 countries/regions between 1990 and 2017.METHODS:Detailed information of 29 cancer groups were collected from the Global Burden of Disease (GBD) study in 2017 and age-standardized incidence rates (ASIR) and age-standardized death rates (ASDR) of 29 cancer groups were calculated based on gender, age, region, and country. Trend analyses were conducted for major cancer types.RESULTS:In 2017, the global death population caused by cancer reached 9 million, which was nearly twice the number in 1990. The ASDR and ASIR of cancer in males were about 1.5 times those of females. Breast cancer showed the highest mortality rate in females in 2017. Individuals aged over 50 are at high risk of developing cancer and the number of cases and deaths in this age group accounted for more than 80% of all cancers in all age groups. Asia has the heaviest cancer burden due to its large population density. Different cancers in varied countries globally have their own characteristics. The ASDR and ASIR of some major cancers demonstrated changes from 1990 to 2017.CONCLUSIONS:Analyses of these data provided basis for future investigations to the common etiological factors, leading to the occurrence of different cancers, the development of prevention strategies based on local characteristics, socioeconomic and other conditions, and the formulation of more targeted interventions.

Background: Liver cancer is one of the leading causes of cancer-related deaths worldwide. The primary causes of liver cancer include hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol consumption, nonalcoholic fatty liver disease, and other factors. Aims: The objective of this study was to evaluate the global and sex-, age-, region-, country-, and etiology-related liver cancer burden, as well as the trends in liver cancer caused by different etiologies. Methods: The causes of liver cancer from 1990 to 2017, including global, regional, and national liver cancer incidence, mortality, and etiology, were collected from the Global Burden of Disease study 2017, and the time-dependent change in the trends of liver cancer burden was evaluated by annual percentage change. Results: The global liver cancer incidence and mortality have been increasing. There were 950,000 newly-diagnosed liver cancer cases and over 800,000 deaths in 2017, which is more than twice the numbers recorded in 1990. HBV and HCV are the major causes of liver cancer. HBV is the major risk factor of liver cancer in Asia, while HCV and alcohol abuse are the major risk factors in the high sociodemographic index and high human development index regions. The mean onset age and incidence of liver cancer with different etiologies have gradually increased in the past 30 years. Conclusions: The global incidence is still rising and the causes have national, regional, or population specificities. More targeted prevention strategies must be developed for the different etiologic types in order to reduce liver cancer burden.

The liver injury induced by Polygonum multiflorum (PM) used for clinical treatment has recently received widespread attention. This study aimed to determine the hepatotoxicity of PM through pharmacokinetics studies. The extract of PM was separated to isolate the anthraquinone fraction, the tannin and polysaccharide fraction, the hydroxystilbene fraction, and the combined anthraquinone fraction. A rapid LC-MS/MS method was developed and validated to simultaneously analyze 2,3,5,4′-tetrahydroxystilbene-2-O-β-glucoside (TSG), emodin-8-O-β-D-glucopyranoside (EDG), and emodin in rat plasma, and was applied to the pharmacokinetics (PK) studies. The hepatotoxicity of different extracted parts of PM was evaluated through the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBil), direct bilirubin (DBil), and indirect bilirubin (IBil) in rat serum. The results showed that liver injury occurred in all the treated groups and that the hepatotoxicity performance of the total extract was different from other groups. The pharmacokinetic studies showed that the Cmax, Tmax, AUC, t1/2, and MRT of the major compounds of different extracted parts were significantly different in rat plasma at same dosage. Emodin-O-hex-sulfate, tetrahydroxystilbene-O-(galloyl)-hex, emodin (original and generated through EDG deglycosylation), and other free anthraquinones might be responsible for the hepatotoxicity of PM in vivo. PM extracts produced inhibitory effects on drug metabolic enzymes, include CYP3A4, CYP2C19, CYP2E1, UGT1A1, etc. And these effects may be related to its hepatotoxicity and pharmacokinetic behavior different. This information on hepatotoxicity and the pharmacokinetic comparison may be useful to understand the toxicological effects of PM.

Background/Aims: Clinical reports on adverse reactions that result from Polygonum multiflorum (PM) and its preparations, especially regarding liver injury, have recently received widespread attention. This study aimed to investigate the mechanism of hepatotoxicity induced by different PM extracts through iTRAQ quantitative proteomics. Methods: The different PM extracts were orally administrated for 90 days to rats, and the hepatotoxicity effect was evaluated through measurement of biochemical indexes, oxidative damage indexes and hematoxylin-eosin (HE) staining. Then, the hepatotoxicity mechanism was investigated by iTRAQ quantitative proteomics. Results: The results of biochemical and histopathological analyses showed that liver injury occurred in all groups of rats given by various PM extracts, which proved all of the PM extracts could induce hepatotoxicity. The hepatotoxicity mechanism may differ between the total extract group and the other groups through the results of biochemical indicators. The iTRAQ proteomics study showed that hepatotoxicity resulting from PM was mainly related to the abnormal activity of mitochondrion function-related oxidative phosphorylation pathways. Conclusion: This iTRAQ proteomics study revealed that the hepatotoxicity induced by PM is primarily related to the oxidative phosphorylation pathways. NADH dehydrogenase family proteins and Slc16a2 could be potential biomarkers of hepatotoxicity resulting from PM.

Herbal medicine has been widely used in the treatment of various diseases; however, the adverse reactions cannot be ignored. Most previous studies have ignored the relationship between the factors of geographical areas/batches and toxicity. This study used Polygonum multiflorum (PM) as an example to analyze the relationship between the geographical areas/batches and toxicity and speculated on the hepatotoxicity-inducing components in PM based on high content screening, UHPLC-Q-TOF/MS and Progenesis QI software analysis. The results of the study show that the toxicity of PM was obviously different among the different geographical areas, and the most toxic PM was from the Sichuan province. To obtain more accurate results and to reduce the false-positive rate, two methods were used to evaluate the speculative results. It was noteworthy that emodin was not the main hepatocyte toxicity constituent of PM. The analysis methods suggested that PM toxicity may be associated with tetrahydroxystilbene-O-(galloyl)-hex and emodin-O-hex-sulfate. The toxicity of these two components requires further study.

Radix polygoni multiflori (RPM) has antioxidative, anti-aging, liver-protective and antihuman cytomegalovirus activity. It has been proved to be hepatotoxic. Considering multiple ingredients to control RPM quality is essential. The aim of this study was to establish a simple, rapid method using resolution liquid chromatography coupled with a triple quadruple mass spectrometry to identify and quantify the major bioactive constituents in RPM. The method was applied to analyze 14 marker batches from manufacturers from the same province. The ultrasonic extracts of all samples were determined by LC-MS/MS, and assessed by hierarchical cluster analysis. The proposed method was applied to analyze 21 batches of samples with acceptable linearity (R(2) , 0.9930-0.9998), precision (relative standard deviation, RSD, 0.45-4.73%) repeatability (RSD, 1.14-9.41%), stability (RSD, 1.29-12.88%) and recovery (RSD, 1.80-12.15%) of the 14 compounds. Furthermore, the hierarchical cluster analysis was applied to classify 21 samples on the basis of characteristics of the 14 compound markers. The developed method was demonstrated to be simple, sensitive and reproducible, and has significant importance and comprehensive evaluation for quality control of RPM and related preparations. Hierarchical cluster analysis clearly indicated that the RPM from the same province was similar, whereas samples of RPM from different provinces were significantly different.

目的 建立同时测定小柴胡颗粒中甘草苷、黄芩苷、汉黄芩苷、黄芩素、甘草酸铵、柴胡皂苷a和汉黄芩素的HPLC方法,并评价不同厂家及同一厂家不同批次的差异.方法 采用Agilent Eclipse XDB-C18色谱柱(250 mm×4.6 mm,5μm),以乙腈-0.1％磷酸水溶液梯度洗脱,检测波长为210nm,体积流量为0.8 mL/min,柱温为30℃.结果 7种指标成分的线性关系均良好.不同厂家样品质量差异较大,同一厂家不同批次样品质量差异相对较小.结论 该方法科学合理,能相对较全面地反映小柴胡颗粒的质量,为客观评价其质量提供科学依据.

Currently,most of university education models are difficult achieves the standard that possessing good practice ability and innovation ability,which is an important barometer for teaching quality.Pharmaceutical forum can fully promote the enthusiasm and initiative of students,cultivate them independent thinking ability and improve innovation ability accordingly.Both shortcomings and disadvantages of our graduate student's innovative education and the effects of pharmaceutical forum on TCM postgraduates are mainly discussed in this paper.

To establish a fingerprint of Xiaochaihu granules sold in the market with HPLC method, and study fingerprints of Xiaochaihu granules produced by different manufacturers and in different batches of the same manufacturer. Seven major index components were identified for the first time. The established method provided an all-around analysis on the quality assessment of Xiaochaihu granules.

Objective:To establish a simple,feasible and precise quality control strategy for determination of concentration and entrapment efficiency of isopropylidene shikimic acid liposome.Method:Chromatographic conditions were:Agilent Eclipse Plus C18 column(4.6 mm×100 mm,3.5 μm),column temperature of 30 ℃,mobile phase of acetonitrile-0.05% phosphoric acid solution(10:90),flow rate of 1.0 mL·min-1,injection volume of 20 μL and detection wavelength at 220 nm.The content of ISA in liposomes was determined by HPLC;Encapsulation efficiency was determined by ultrafiltration,gel chromatography and dialysis method,respectively,and results were compared with each other.Result:After demulsification by adding 4 times the amount of methanol into ISA liposome and high speed centrifugal sedimentation,supernatant was used to determine,determination results showed a good specificity,precision and accuracy,regression equation showed a good linearity(r=0.999 9) within range of 1.004-150.6 mg·L-1,recovery was(102.01±1.18)%,reference substance solution of ISA was stable in 6 h;Entrapment efficiency of ISA liposome determined by ultrafiltration method,gel permeation method and dialysis method were(92.96±1.91)%,(91.23±2.23)%,(73.66±7.10)%,respectively.Conclusion:This established HPLC method was stable and reliable,it could be used for quality control and in vitro analysis;In determination of encapsulation efficiency,ultrafiltration method was simple and efficient,its results were close to gel permeation chromatography;Due to limit of measurement conditions,determination result of dialysis method might be lower for its time-consuming process and higher temperature,and also depending on stability of liposome solution and existence state of drugs in liposome.

A rapid and specific RP-HPLC-UV method was developed for the analysis of polyphyllin II and hyperoside in beagle dog plasma. The analysis was carried out on a Diamonsil C-18 (2) reversed-phase column (250 x 4.6 mm, 5 mm) by isocratic elution with acetonitrile and 0.1 % phosphoric acid (50: 50, v/v). The flow rate was 1.0 mL/min and the detection wavelength was set at 203 nm and 360 nm. Linear responses were obtained for polyphyllin II ranging from 3.3333 to 100 mu g/mL and hyperoside ranging from 2 to 60 mu g/mL. The intra and interday precisions (RSDS) were less than 9.23 and 9.24 % with the accuracy (%) ranging from 89.67 to 107.25 %. The extraction recovery, ranged from 84.97 to 91.32 % with RSD less than 7.381 %. Stability studies showed that two compounds were Stable in analytical process. In the pharmacokinetic interaction study, present findings indicate that polyphyllin II and hyperoside have a clear effect on the pharmacokinetic behaviour.

A rapid and specific LC-MS/MS method has been developed for the simultaneous analysis of polygala acid, senegenin and 3,6'-disinapoylsucrose (DSS) in rat plasma. The method was applied to the pharmacokinetics studies of polygala acid, senegenin and DSS. The analysis was carried out on an Agilent Eclipse plus C18 reversed-phase column (100 × 4.6 mm, 3.5 µm) by gradient elution with methanol and ammonia (0.01%, v/v). The flow rate was 0.4 mL/min. All analytes including internal standard (IS) were monitored by selected reaction monitoring with an electrospray ionization source. Linear responses were obtained for polygala acid and DSS ranging from 2.5 to 2000 ng/mL, and senegenin ranging from 5 to 2000 ng/mL. The intra- and inter-day precisions (relative standard deviation) were <11.34 and 8.99%. The extraction recovery ranged from 70.89 ± 4.60 to 88.49 ± 3.26%, and that for the IS was 77.23 ± 3.68%. Stability studies showed that polygala acid, senegenin and DSS are stable during the preparation and analytical process. The validated method was successfully used to determine the concentration-time profiles of polygala acid, senegenin and DSS.

For the first time, a rapid and specific LC-MS-MS method has been developed for the analysis of polyphyllin I, polyphyllin II, polyphyllin VI and polyphyllin VII in beagle dog plasma. The method was applied to study the pharmacokinetics of Rhizoma Paridis extracts containing polyphyllin I, polyphyllin II, polyphyllin VI and polyphyllin VII. The analysis was carried out on an Agilent Zorbax XDB-C(18) reversed-phase column (100 × 2.1 mm, 1.8 µm) by isocratic elution with acetonitrile and water (50:50, v/v). The flow rate was 0.25 mL/min. All analytes including internal standards were monitored by selected reaction monitoring with an electrospray ionization source. Linear responses were obtained for polyphyllin I, polyphyllin II, polyphyllin VI and polyphyllin VII ranging from 10 to 5000 ng/mL. The intra-and inter-day precisions (RSDs) were less than 6.66 and 9.15%. The extraction recovery ranged from 95.53 to 104.21% with RSD less than 8.69%. Stability studies showed that polyphyllin I, polyphyllin II, polyphyllin VI and polyphyllin VII were stable in preparation and analytical process. The validated method was successfully used to determine the concentration-time profiles of polyphyllin I, polyphyllin II, polyphyllin VI and polyphyllin VII.

Objective:To study the effect of Scutellaria extract to cytochrome P450 enzymes CYP1A2 CYP3A4,CYP2E1 and CYP2C19.Method: To establish an RP-HPLC method for the study of 4 probe drugs in rats plasma.The rats are divided in 2 groups randomly.One group were given Scutellaria extract once daily,another received normal saline once daily as the blank control.After 10 days of treatment,the rats were given 4 probe drugs by tail intravenous injection and the plasma were obtained at 0,5,10,15,30,15,60,180,360,540,720 min.The plasma concentration of 4 probe drugs was determined by RP-HPLC.The pharmacokinetic parameters were calculated by Kinetica 5.0.Result: The metabolism of dapsone,chlorzoxazone and omeprazole are slowed down significantly while the T1/2of all 4 probe drugs were increased.The MRT0→∞of chlorzoxazone and omeprazole were increased significantly.Conclusion:Scutellaria extract tended to be the inhibitor of CYP1A2,CYP3A4,CYP2E1 and CYP2C19.But CYP3A4 and CYP2E1 were affected significantly.

Objective: To develop an HPLC method for determination of related substances of isopropylidene-shikimic acid with UV detection.Methods:The related substances of isopropylidene-shikimic acid were separated on an Agilent Zorbax Eclipse XDB-C18 column(4.6 mm×250 mm,5 μm) with a mobile phase consisting of acetonitrile-0.05% phosphoric acid(7∶ 93) at a flow rate of 1.0 mL·min-1 and detected at a wavelength of 220 nm,column temperature was 30 ℃.Results:The resolution and sensitivity of related substances were acceptable.The detection limit was 1 ng.Conclusions:The method is simple and selective.It can be used for the determination of releted substances of isopropylidone shikimic acid.

OBJECTIVETo study the plasma protein binding rate of isopropylidene-shikimic acid.METHODThe ultrafiltration was employed to determine the plasma protein binding rate of isopropylidene-shikimic acid. The plasma concentrations of isopropylidene-shikimic acid were measured by HPLC.RESULTThe plasma protein binding rate of isopropylidene-shikimic acid with dog plasma at the concentration of 0.3, 0.15 g x L(-1) and 0.5 mg x L(-1) were (4.36 +/- 0.02)%, (4.12 +/- 0.19)% and (2.23 +/- 0.59)%, respectively. While the plasma protein binding rate of isopropylidene-shikimic acid with normal human plasma at the above concentrations were (11.23 +/- 0.01)%, (10.06 +/- 0.69)% and (9.72 +/- 0.59)%, respectively.CONCLUSIONThe binding rate of isopropylidene-shikimic acid with plasma protein is low.