Cloning and functional characterization of isopentenyl diphosphate isomerase genes from Panax vietnamensis var. fuscidiscus / 药学学报

Isopentenyl diphosphate isomerase (IDI) is a key enzyme in the regulation of triterpenes biosynthesis and plays an important role in ginsenoside biosynthesis. In this study, two IDI genes, PvfIDI1 (GenBank No. MZ736417) and PvfIDI2 (GenBank No. MZ736418) were cloned from Panax vietnamensis var. fuscidiscus. The open reading frame of both PvfIDI1 and PvfIDI2 was 924 bp encoding 307 amino acids. The molecular weights of PvfIDI1 and PvfIDI2 were 34.84 kDa and 34.66 kDa, respectively, with theoretical pIs of 6.01 and 5.66. Bioinformatic analysis indicated that PvfIDI1 and PvfIDI2 contained two conserved sequences: TNTCCSHPL and WGEHELDY. Phylogenetic analysis showed that PvfIDI1 and PvfIDI2 were closely related to Panax notoginseng IDI. Expression analysis showed that both PvfIDI1 and PvfIDI2 genes are expressed in root, rhizome, stem and leaf of P. vietnamensis var. fuscidiscus. However, PvfIDI1 is highly expressed in the rhizome and PvfIDI2 is highly expressed in the stem. PvfIDI1 and PvfIDI2 recombinant proteins were expressed in E. coli; a functional coloration experiment showed that PvfIDI1 and PvfIDI2 could promote the accumulation of lycopene, indicating that both PvfIDI1 and PvfIDI2 encode functional IDI enzymes. The cloning and functional studies on PvfIDI1 and PvfIDI2 provide a foundation for the further study of IDI and the regulation of ginsenoside biosynthesis in P. vietnamensis var. fuscidiscus.

Selection of optimal qRT-PCR reference genes for Aconitum vilmorinianum / 中国中药杂志

Screening suitable reference genes is the premise of quantitative Real-time PCR(qRT-PCR)for gene expression analysis. To provide stable reference genes for expression analysis of genes in Aconitum vilmorinianum, this study selected 19 candidate re-ference genes(ACT1, ACT2, ACT3, aTUB1, aTUB2, bTUB, 18S rRNA, UBQ, eIF2, eIF3, eIF4, eIF5, CYP, GAPDH1, GAPDH2, PP2A1, PP2A2, ACP, and EF1α) based on the transcriptome data of A. vilmorinianum. qRT-PCR was conducted to profile the expression of these genes in the root, stem, leaf, and flower of A. vilmorinianum. The Ct values showed that 18S rRNA with high expression level and GAPDH2 with large expression difference among organs were not suitable as the reference genes. NormFinder and geNorm showed similar results of the expression stability of the other candidate reference genes and demonstrated PP2A1, EF1α, and CYP as the highly stable ones. However, BestKeeper suggested EF1α, ACT3, and PP2A1 as the top stable genes. In view of the different results from different softwares, the geometric mean method was employed to analyze the expression stability of the candidate re-ference genes, the results of which indicated that PP2A1, EF1α, and ACT3 were the most stable. Based on the comprehensive analysis results of geNorm, NormFinder, BestKeeper, and geometric mean method, PP2A1 and EF1α presented the most stable expression in different organs of A. vilmorinianum. PP2A1 and EF1α were the superior reference genes for gene expression profiling in different organs of A. vilmorinianum.

Evaluation of blood pressure lowering effect by generic and brand-name antihypertensive drugs treatment: a multicenter prospective study in China / 中华医学杂志(英文版)

BACKGROUND@#Generic drugs are bioequivalent to their brand-name counterparts; however, concerns still exist regarding the effectiveness and safety of generic drugs because of small sample sizes and short follow-up time in most studies. The purpose of this study was to evaluate the long-term antihypertensive efficacy, cost-effectiveness and cardiovascular outcomes of generic drugs compared with brand-name drugs.@*METHODS@#In a multicenter, community-based study including 7955 hypertensive patients who were prospectively followed up for an average of 2.5 years, we used the propensity-score-matching method to match the patients using brand-name drugs to those using generic drugs in a ratio of 1:2, 2176 patients using brand-name drugs and 4352 patients using generic drugs.@*RESULTS@#There were no significant differences between generic drugs and brand-name drugs in blood pressure (BP)-lowering efficacy, BP control rate, and cardiovascular outcomes including coronary heart disease and stroke. The adjusted mean (95% confidence interval [CI]) of systolic BP (SBP)-lowering was -7.9 mmHg (95% CI, -9.9 to -5.9) in the brand-name drug group and -7.1 mmHg (95% CI, -9.1 to -5.1) in the generic drug group after adjusting for age, sex, body mass index, number of antihypertensive drugs and traditionally cardiovascular risk factors. Among patients aged <60 years, brand-name drugs had a higher BP control rate (47% vs. 41%; P = 0.02) and a greater effect in lowering SBP compared with generic drugs, with the between-group difference of 1.5 mmHg (95% CI, 0.2-2.8; P = 0.03). BP control rate was higher in male patients using brand-name drugs compared with those using generic drugs (46% vs. 40%; P = 0.01). Generic drugs treatment yielded an average annual incremental cost-effectiveness ratio of $315.4 per patient per mmHg decrease in SBP compared with brand-name drugs treatment.@*CONCLUSIONS@#Our data suggested that generic drugs are suitable and cost-effective in improving hypertension management and facilitating public health benefits, especially in low- and middle-income areas.

Preparation and quality evaluation of levocarnitine thermosensitive in situ gel / 药学学报

In this paper, a new type of preparation for treatment of initial dry eye disease, thermosensitive in situ gel, was prepared using levocarnitine as a model drug. Poloxamer 407 and poloxamer 188 were used as the gel matrix, and sodium hyaluronate and sodium carboxymethylcellulose were used as bioadhesive materials. Gelation temperature was determined by a rotor method and the prescription was optimized by central composite design-response surface methodology. The pH value, viscosity value and gelation temperature of the optimal prescription were measured. The release of the drug in vitro was examined by dialysis membrane permeation, and retention time of the thermosensitive in situ gel preparation on the rabbit's ocular surface was observed by a slit lamp microscope. The results showed that the dosage of the poloxamer 407 and poloxamer 188 were 20.81% and 3.46%, respectively, and sodium hyaluronate was 0.02%, sodium carboxymethyl cellulose was 0.10% of the optimal formulation of levocarnitine thermosensitive in situ gel. The pH value was 6.90 ± 0.06 at room temperature and the viscosity value started to rise sharply at 27 ℃ of the optimal formulation. The gelation temperature of the optimal preparation before and after dilution by simulated tear fluid were (26.37 ± 0.06) ℃ and (33.57 ± 0.21) ℃, respectively. In the first 240 min, in vitro release rate per unit area of levocarnitine thermosensitive in situ gel was lower than that of solution (P<0.05), and after 600 min, the cumulative release rate of levocarnitine thermosensitive in situ gel could reach more than 80%. The retention time of the thermosensitive in situ gel preparation on rabbit's ocular surface reached about 25 min, at least 5 times as much as that of the solution. The animal experiment was conducted following the National Institutes of Health Guidelines for the use of experimental animals, and approved by the Ethics Committee of the Experimental Animal Center of Beijing University of Chinese Medicine. The levocarnitine thermosensitive in situ gel showed good characteristics and sustained release property and significantly improved the retention time of the drug on the rabbit's ocular surface.

Effect of PEG400 Concentration in Receiving Solution on Drug Transdermal Test in Vitro / 中国实验方剂学杂志

Objective: To investigate the effect of varying concentrations of polyethylene glycol(PEG)400 in receiving solution on in vitro transdermal test of drugs. Method: 5-Fluorouracil(5-FU) was selected as a model drug,by preparing different concentrations of PEG400-phosphate buffer solution(PBS) as the receiving solution,the receiving chamber did not add drug,the excised rat skins were treated with various additives for 12 h,then replaced by PBS and added the saturated model drug into the donor compartment to determine the transdermal parameters of the drug.Meanwhile,scanning electron microscopy(SEM) was employed to monitor the effect of PEG400 with different concentration on the stratum corneum of rat skin. Result: The 10%,15% and 40% PEG400-PBS groups had no significant effect on in vitro transdermal absorption parameters of the 5-FU.The steady transdermal rate and cumulative penetration rate of the drug in 20% and 30% PEG400-PBS groups were significantly higher than that in the PBS group(PPConclusion: In the rat skin transdermal test,the concentration of PEG400 in receiving solution should be controlled below 20%.

Recent development in hypertension gene study / 中国实用内科杂志

Genetic as well as genomic study has advanced the development of precision medicine. We are marching on the road for right patients who are receiving more and more right treatment at right time. In hypertension field, precision medicine is available, actionable and affordable. First and the most practical advancement is monogenic hypertension, the disease-genes have been found for at least 17 types of monogenic hypertension. These patients can be precisely treated according to their carried gene mutation. Secondly, pharmacogenetic and pharmacogenomic guided anti-hypertensive drug selection, very promising but lack of clinic outcome data to support widely clinical application. Majority of hypertension are due to multiple genetic and environmental factors. GWAS fund some genetic variants related to primary hypertension, but these variants can only be responsible for 1-10% of blood pressure variation. We have a long way to go in exploring the real cause of primary hypertension.

Analysis and consideration based on first classical prescriptions / 中国中药杂志

Classical prescriptions are precious wealth left by ancient Chinese medical scientists. Moreover,they are also the important part of the treasure-house in Chinese medicine. Classical prescriptions have a long and rich history for human-use in China and play an important role in keeping people healthy. The state administration of traditional medicine of China published the Catalogue of Classical Prescriptions(first batch) in 2018. This measure has inspired the enthusiasm of Chinese medicine manufacturers to study ancient classical prescriptions and develop classical compound prescriptions. Based on the first batch of classical prescriptions, the dosage forms, sources, prescription components, decocting degree, use of toxic drugs and processing methods of classical prescriptions. The results showed that most of the classical prescriptions in the first batch were decoction and boiled powder,while only four of them were powder and paste forms,all of which were originated from representative classics in the past dynasties. The dosage and decocting degree of decoction were greater than those of boiled powder. The dosage and decocting degree of decoction in Han and Tang Dynasties was close to that in Ming and Qing Dynasties,higher than that in Song and Jin Dynasties. Moreover,the average number of herbs in the prescriptions in Han Dynasty was the smallest. The use of toxic traditional Chinese medicine was the most frequent in Han Dynasty, and Pinellia ternata was the most common toxic medicine. There were various processing methods, including cleansing, cutting, stir-frying, roasting and so on. In this paper, the dosage forms of traditional paste, the time concept of decoction in the ancient times, the traditional roasting method and the processing method of toxic drugs were summarized to provide ideas and reference for further development of classical prescriptions.

Research progress on selection of matrix and adding methods of volatile oil in Chinese materia medica cataplasma / 中草药

Cataplasma is a new transdermal drug delivery carrier, playing a significant role in the modernization of Chinese materia medica (CMM). It can overcome many shortcomings such as inconvenient use and intense irritation in traditional adhesive plaster and black plaster. However, the development of cataplasma is restricted by some crucial factors like the types of auxiliary materials and the processing ways of volatile medicine. A total of 254 articles related to CMM cataplasma optimization and the volatile oil treatment published from 2000 to 2017 were collected and sorted in this paper. The matrix types and excipients ratio scope, the experiment design method of optimized ratio of base material, and the processing ways of volatile oil in cataplasma were summarized, and then the existing problems in these three aspects mentioned above were discussed with view to giving reference for follow-up studies.

Effect of the smoking cessation services in the out-patient department for patients with coronary heart disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the effects and clinical prognosis of out-patient department-based smoking cessation services for coronary heart disease (CHD) patients.</p><p><b>METHODS</b>A total of 140 smoking patients diagnosed with coronary heart disease in our cardiovascular department were randomly divided into the intensive smoking cessation clinic follow-up group (intervention group, patients were informed on the importance and methods to quit smoking at the first visit and reminded for that at months interval for 6 months, n = 70) and the conventional treatment group (control group, n = 70). After 6 months, the smoking status, cardiovascular event rates, drug usage, out-patient medical costs and quality of life were compared between the two groups.</p><p><b>RESULTS</b>Age, gender, concomitant diseases, drug usage were similar between the two groups at baseline (all P > 0.05). After 6 months, smoking quit rate [34.2% (24/70) vs. 5.7% (4/70), P < 0.01], drug use rates: lipid-lowering drugs [95.3% (67/70) vs. 80.4% (56/70)], β blockers [82.4% (57/70) vs. 41.3% (28/70)], and ACEI/ARB [61.4% (43/70) vs. 34.4% (24/70)] were significantly higher in the intervention group than in the control group, while total cardiovascular event rates [21.4% (15/70) vs. 47.1% (33/70), P < 0.01] and out-patient medical costs (3789.3 RMB vs. 4984.2 RMB, P < 0.01) were significantly lower in the intervention group than in the control group. The quality of life scores derived from MYO health survey questionnaire was significantly higher in the intervention group than in the control group (P < 0.01). The top three reasons responsible for continuous smoking for all patients failed to quit smoking were: (1) others smoked more than me and still alive and healthy [90.3% (56/62)]; (2) smoking helped me to keep relaxed and reduce trouble in daily work and life [70.9% (44/62)]; (3) smoking was essential while chatting and drinking with friends [66.1% (41/62)]. The overall satisfactory rate to this smoking cessation program was 42.8% and the satisfactory rate was up to 50.0% by patients.</p><p><b>CONCLUSIONS</b>Intensive outpatient smoking cessation follow-up program can significantly improve the smoking cessation rates, the guideline drug use rate and the quality of life while reduce medical costs for coronary heart disease patients.</p>

Recent researches of synthetic mercury sulfide in traditional medicine system / 中国中药杂志

<p><b>OBJECTIVE</b>Herein, the synthesis, component, microstructure and pharmacological and toxicology researches of the Synthetic Mercury Sulfide (S-HgS) a kind of common drug in Chinese, Mongolia, Tibetan medicine, and Indian medicine system were summarized. The similar cognition about mercury toxicity & pharmacological action from some Asian regions was analyzed, and it can supply some useful direction for the traditional Asian medicine system.</p><p><b>METHOD</b>Recent literatures both domestic and abroad were summarized and analyzed.</p><p><b>RESULT</b>S-HgS is the basis of Vermilion, Mongolia-Vermilion, Zuotai, and Ras-sindoor. Athough the processes of synthesis are very different, but the microstructure and pharmacological & toxicology of S-HgS is similar.</p><p><b>CONCLUSION</b>S-HgS has a far-ranging application,and unique curative effect. New technology such as nanotechnology can be used for improving the advancement of traditional Asian medicine.</p>

Comparative effects of Roux-en-Y gastric bypass procedures preserving different gastric volume on blood glucose in Goto-Kakizaki rats / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the effects of Roux-en-Y gastric bypass (RYGBP)procedures preserving different gastric volume on blood glucose of rats with non-obese type 2 diabetes.</p><p><b>METHODS</b>A total of 36 Goto-Kakizaki rats randomly underwent one of the following procedures: gastric bypass with different types of anastomosis including the Roux-en-Y of total stomach excision(n=12), the Roux-en-Y of partial stomach excision(n=12) and the Roux-en-Y of stomach preservation(n=12). Rats were observed for 24 weeks after surgery. Body weight, food intake and fasting blood glucose level were tested at 0(preoperative), 1, 3, 6, 12, 24 weeks. Hemoglobin A1c(HbA1c) level was measured at 0, 12, 24 weeks and glucose tolerance test (OGTT) was performed in conscious rats before (baseline) and then 30, 60, 120, and 180 minutes. Change of blood glucose over time was depicted. Area under curve(AUC) of glucose tolerance were calculated.</p><p><b>RESULTS</b>Compared with preoperative levels, the weight and food intake of all the rats were significantly decreased at 1 week after surgery(P<0.01). At 3 weeks after operation, the weight and food intake were significantly increased compared with 1 week after operation in the Roux-en-Y of partial stomach excision and the Roux-en-Y of stomach retention(P<0.01). In the Roux-en-Y of total stomach excision, the weight and food intake were significantly lower compared with other two groups(P<0.05). At 24 weeks after operation, the levels of fasting blood glucose were (7.3 ± 1.5), (7.5 ± 2.0) and (8.3 ± 1.3) mmol/L, which were lower than the preoperative levels [(13.2 ± 1.6), (13.6 ± 2.5) and (12.9 ± 2.0) mmol/L, P<0.01] in the three groups. There were no significant differences among the three groups(P>0.05). At 24 weeks after operation, the HbA1c levels were(6.3 ± 1.3)%, (6.4 ± 2.0)% and (7.0 ± 1.3)%, which were lower than the preoperative level[(10.2 ± 2.6)%, (9.6 ± 2.5) and (9.9 ± 2.0)%, P<0.01]. There were no significant differences among the three groups(P>0.05). The trend of the glucose tolerance test and AUC were similar in the three groups after operation.</p><p><b>CONCLUSION</b>Roux-en-Y gastric bypass in non-obese diabetic rats is effective in terms of glucose control and the efficacy of gastric bypass has no obvious association with the stomach volume.</p>

Variants of tumor necrosis factor-induced protein 3 gene are associated with left ventricular hypertrophy in hypertensive patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tumor necrosis factor-induced protein 3 (TNFAIP3) gene has been shown important in cardiac remodeling. The aim of the present study was to investigate whether the variants of TNFAIP3 gene are associated with left ventricular hypertrophy (LVH) in hypertensive patients.</p><p><b>METHODS</b>Four representatives of all the other single nucleotide polymorphisms (SNPs) in TNFAIP3 gene were tested for association with hypertrophy in two independent hypertensive populations (n = 2120 and n = 324).</p><p><b>RESULTS</b>We found that only the tag SNP (rs5029939) was consistently lower in the hypertensives with cardiac hypertrophy than in those without cardiac hypertrophy in the two study populations, indicating a protective effect on LVH (odds ratio (OR) (95% confidence interval (CI)) 0.58 (0.358 - 0.863), P = 0.035; OR (95%CI) = 0.477 (0.225 - 0.815), P < 0.05, respectively). Multiple regression analyses confirmed that the patients with G allele of rs5029939 had less thickness in inter-ventricular septum, left ventricular posterior wall, relative wall thickness and left ventricular mass index than did those with CC allele in the hypertensive patients in both study populations (all P < 0.01).</p><p><b>CONCLUSION</b>These findings indicate that the SNP (rs5029939) in the TNFAIP3 gene may serve as a novel protective genetic marker for the development of LVH in patients with hypertension.</p>

Research progress in the in vitro culture of testicular spermatogenic cells / 中华男科学杂志

The production of sperm is a very complicated and orderly process, which involves the proliferation and differentiation of cells. The in vitro culture of spermatogenic cells includes tissue culture and cell culture. This study focuses on the advances in the in vitro culture of spermatogenic cells, testicular tissue culture and their culture conditions, and sums up the advantages and disadvantages of various culture methods, in an attempt to find the best method for differentiating spermatogenic cells in vitro and make the culture of spermatogenic cells an important means of treating male infertility.

Cardiovascular risk and prevalence of metabolic syndrome by differing criteria / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The prevalence of metabolic syndrome (MetS) in hypertensive population in Chinese countryside is unknown. Firstly, this study compared the prevalence of MetS according to National Cholesterol Education Program (NCEP) ATPIII, revised NCEP and International Diabetes Federation (IDF) definitions. Secondly, it investigated the association between MetS, coronary heart disease (CHD) and stroke in patients with hypertension.</p><p><b>METHODS</b>In this cross sectional study, the cluster sampling method was used. Three MetS definitions were applied to 1418 normal subjects and 5348 hypertensive patients aged 40-75 years in rural areas in China. The agreement between different MetS definitions was estimated by kappa statistics. Logistic regression analyses determined the association between MetS defined by the three MetS definitions and CHD and stroke.</p><p><b>RESULTS</b>In subjects without hypertension, the prevalence of Mets was 4.1% by NCEP definition, 8.3% revised NCEP definition and 7.8% IDF definition. In hypertensive individuals, the prevalence was 14.0%, 32.9%, and 27.4% in men; 35.6%, 53.1%, and 50.2% in women by the same definitions, respectively. In hypertensive individuals, the agreement was 94.4% in men and 97.0% in women between revised NCEP and IDF definitions. The IDF defined MetS was more strongly associated with CHD than the NCEP or revised NCEP defined MetS (adjusted odds ratio: 1.92 compared with 1.85 and 1.69 in men; 1.64 compared with 1.48 and 1.60 in women).</p><p><b>CONCLUSIONS</b>In the patients with hypertension, the revised NCEP and IDF definitions identified more individuals than NCEP definition and their agreement is very high. The IDF defined MetS is more strongly associated with CHD than the NCEP or revised NCEP defined MetS, but weakly or not associated with stroke.</p>

Ghrelin receptor gene polymorphisms are associated with female metabolic syndrome in Chinese population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The ghrelin plays an important role in the regulation of food intake and energy homeostasis. Therefore, the ghrelin receptor gene (GHSR) is an excellent candidate for studying metabolic syndrome. This study aimed to investigate whether polymorphisms in ghrelin receptor gene are associated with metabolic syndrome in Chinese population.</p><p><b>METHODS</b>Subjects consisted of 698 patients aged 41 to 80 years, diagnosed as metabolic syndrome by International Diabetes Federation (IDF) 2005 criteria, and 762 age- and gender-matched controls. Three variants within the GHSR were selected and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Odds ratios were estimated using a case-control study design by controlling confounding factors.</p><p><b>RESULTS</b>The A/A genotype (rs2922126) in the promoter was associated with metabolic syndrome (OR 1.41, 95% CI 1.03-1.94), increased waist circumference (OR 1.75, 95% CI 1.26-2.42), and increased fast blood glucose (OR 1.49, 95% CI 1.07-2.06) in women. The A/A genotype (rs509030) in the intron was associated with lower plasma high density lipoprotein in women (OR 1.37, 95% CI 1.02-1.84).</p><p><b>CONCLUSION</b>The polymorphisms within GHSR might be a genetic risk factor for metabolic syndrome in women.</p>