Effects of UGT1A1, CYP3A5 and ABCB1 Genetic Variants on Pharmacokinetics of Antihistamine Drug Mizolastine in Chinese Healthy Volunteers

Mizolastine is a selective histamine H1 receptor antagonist for chronic urticaria or allergic rhinitis. We investigated whether the variant genotypes of metabolic enzymes UGT1A1, CYP3A5 and transporter ABCB1 influence pharmacokinetic phenotype of substrate mizolastine in Chinese volunteers. Genotyping of single nucleotide polymorphisms in UGT1A1*6 (G211A), CYP3A5*3 (A6986G) and ABCB1 (C3435T) was determined by the pyrosequencing method. After a single oral dose of 10 mg mizolastine, the plasma concentrations were measured using validated high‐performance liquid chromatography in 24 Chinese healthy volunteers. The results showed that the distributions of wild‐type homozygotes and variant allele carriers (the sum of variant heterozygotes and variant homozygotes) were as follows: 17 cases (70.8%) versus seven cases (29.2%) in UGT1A1*6 genotypes, five cases (20.8%) versus 19 cases (79.2%) in CYP3A5*3 genotypes and seven cases (29.2%) versus 17 cases (70.8%) in ABCB1 3435T genotypes, respectively. There were no significant differences in pharmacokinetic parameters of mizolastine between the variant allele UGT1A1*6, CYP3A5*3 and ABCB1 3435T carriers and the wild‐type homozygotes, and the ratios were as follows: C_max was 101.03%, 86.02% and 105.78%; T_max was 162.35%, 98.98% and 144.90%; AUC_0–28 was 113.04%, 77.35% and 112.71%; and t_1/2 was 95.77%, 72.40% and 100.97%, respectively. In conclusion, these results suggested that the UGT1A1, CYP3A5 and ABCB1 genetic polymorphisms might be not contributed to the interindividual variation of mizolastine pharmacokinetic phenotype in the Chinese population.     

刺人参挥发油成分及其抗真菌活性的研究

Oplopanax elatus (Ci Ren Shen, in Chinese), a perennial bush with thorn, wildly grows in Chang Bai Mountain area, northeast China. The essential oil of its root, rhizome and stem was extracted by steam distillation with yields of 0.8～1.2%. By means of GC/MS/DS, 31 chemical constituents were identified as follows: n-hexanal (0.22%), heptaldehydc (0.17%), α-pinene (1.30%), β-pentyl furan(0.27%), n-octanal(2.07%), limonene(0.31%), ocimene(1.62%), δ-3-carene(0.19%), perillen(1.33%), 2,6-dimethyl heptalene(1.07%), borneol(1.27%), α-dodecenal(7.14%), α-copaene(0.54%), tetradcanal(1.17%), iaocaryophyllene (0.58%), β-farnesene(0.92%), α-caryophyllene(0.82%), γ-muurolene(0.73%), longifolene(1.67%), 3, 7, 11-trimethyl-2, 6, 10-dodinene(8.64%), γ-cadinene(2.79%), δ-cadinene(5.03%), nerolidol(14.93%), gualol(4.20%), torreyol(10.0%), cedrol(4.24%), bulnesol(7.79%) and farnesol(1.16%).The antimycotic activities of Ci Ren Shen cssential oil was determined in vitro by serial dilutions on solid nutrient medium. Fungistatic results were visible on 5 species, Microporum gypseum, M. lanosun, Trichophyton gypseum, T. purpureatum and Epidermophyton floccosum. The MIC is 0.0625%.     

Alliin obtained from leaf extract of garlic grown under in situ conditions possess higher therapeutic potency as analyzed in alloxan-induced diabetic rats

Context: Garlic, Allium sativum L. (Liliaceae), possesses high therapeutic and pharmacological properties. Hypoglycemic activity is attributed to alliin (S-allyl cysteine sulfoxide), the main active principle localized in garlic cloves.

Objective: To compare the production and therapeutic efficiency of alliin extracted from garlic leaves of plants grown under ex situ and in situ conditions.

Materials and methods: Alliin content of leaves was quantified and aqueous leaf extracts (from ex situ and in situ grown plants) were given to normal and alloxan-induced diabetic rats for five weeks.

Results: Alliin production noted ~50% enhancement in leaves from plants grown under in situ conditions. Serum glucose, triglycerides, total lipids, total cholesterol, low-density lipoprotein (LDL)-, and very low-density lipoprotein (VLDL)-cholesterol in diabetic rats treated with alliin produced from in situ grown plants noted significant reduction of ~54%, 15%, 14%, 20%, 24%, and 15%, while 35%, 14%, 10%, 12%, 17% and 11% reduction was noted in diabetic rats treated with alliin produced from ex situ grown plants in comparison with those administered with distilled water. High-density lipoprotein (HDL)-cholesterol did not show any significant change. Leaf extract of plants lowered serum enzyme levels (alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase) toward the norm better than glibenclamide. The histopathological alteration in pancreas caused by alloxan was also reduced by leaf extract.

Discussion and conclusion: These findings demonstrate leaf extract obtained from plants grown under in situ condition possess higher therapeutic efficiency in comparison with leaf extract obtained from plants grown under ex situ condition. Studies suggest that environmental factors influence production of alliin and its therapeutic potential.     

Polymorphisms in CYP2D6 have a Greater Effect on Variability of Risperidone Pharmacokinetics than Gender

Within‐subject coefficient of variation (CV_w) plays a decisive role in the determination of sample size in bioequivalence clinical trials. Highly variable drugs may require the participation of a large number of subjects. The aim of this study was to investigate whether gender and polymorphisms in CYP2D6 affect the CV_w of risperidone. Two single‐dose, two‐period crossover studies of risperidone (n = 70) were reanalysed to calculate CV_w for AUC_t and C_max. Subjects were classified into four different CYP2D6 phenotype groups [poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM) and ultrarapid metabolizers (UM)]. The effect of gender was evaluated in EM and IM. CV_w was lower in PM (13.3% for AUC_t and 10.9% for C_max) and UM (17.4% and 8.7%) than in EM (28.7% and 34.7%) and IM (33.2% and 27.3%). Variability was slightly lower in women (27.9% for AUC_t and 25.7% for C_max) than in men (33.3% and 37.2%, respectively). Genetic polymorphisms affect within‐subject variability more than gender and could considerably affect sample size calculation. Therefore, subjects participating in bioequivalence trials should be genotyped.     

碳青霉烯耐药肠杆菌科细菌临床分布及耐药特征分析

目的 分析综合性三甲医院住院患者临床标本分离碳青霉烯耐药肠杆菌科细菌（CRE）的临床分布及耐药特征,为临床抗感染治疗及院感防控提供参考。方法 收集2015年7月至2017年6月安徽医科大学第二附属医院住院患者临床标本分离CRE药敏数据及相关临床资料,应用WHONET 5.6软件统计分析CRE临床分布及耐药率,药敏折点参照CLSI 2016版标准。结果 2015年7月至2017年6月期间,自住院患者临床标本共分离CRE 82株,由肺炎克雷伯菌（42株,51.22%）、大肠埃希菌（23株,28.05%）、阴沟肠杆菌（9株,10.98%）、黏质沙雷菌（5株,6.10%）、弗劳地枸橼酸杆菌（2株,2.44%）及产酸克雷伯菌（1株,1.22%）构成。临床标本以痰标本（29株,35.37%）,分泌物/脓液标本（20株,24.39%）及尿液标本（14株,17.07%）为主。CRE分布广泛,检出的临床科室包括ICU（14株,17.07%）、呼吸内科（10株,12.20%）等。CRE菌株对临床常用抗菌药物耐药性较高,仅对阿米卡星较为敏感,耐药率为23.17%。结论 CRE菌株临床分布广泛且对常用抗菌药物耐药率高,临床科室应积极送检病原学检验并根据药敏结果合理选择抗菌药物。医院感控部门应联合微生物实验加强对CRE菌株的监测与防控。     

Prevalence of CYP2B6 alleles in malaria-endemic populations of West Africa and Papua New Guinea

Objective Cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of artemisinin drugs, a novel series of antimalarials. Our aim was to analyze the prevalence of the most commonly observed CYP2B6 alleles in malaria-endemic populations of West Africa (WA) and Papua New Guinea (PNG). Methods Using a post-PCR ligation detection reaction-fluorescent microsphere assay, frequencies of CYP2B6*1A, *2, *3, *4, *5, *6, *7, and *9 were determined in WA (n=166) and PNG (n=174). To compare with the results of previous studies, we also determined the allele frequencies in 291 North Americans of various ethnic groups. Results Significant differences were observed between WA and PNG for the frequencies of alleles CYP2B6*1A (45% vs 33%, P = 0.003), *2 (4% vs. 0%, P<0.001), *6 (42% vs 62%, P<0.001), and *9 (8% vs 1%, P<0.001), and genotypes *1A/*9 (9% vs 0%, P<0.001) and *6/*6 (17% vs 43%, P<0.001). The frequencies of CYP2B6 genotypes in the populations were in Hardy-Weinberg equilibrium, except for PNG where an overall significant deficit of heterozygosity was observed (H _O=0.431, H _E=0.505, P=0.004). The allele frequencies in Asian-Americans and Caucasians-Americans were comparable to those documented for Japanese and Caucasian populations. Conclusions CYP2B6 variants, previously shown to affect metabolism of a variety of drugs, occur in WA and PNG, and there are significant genetic differences at the CYP2B6 locus in these populations. It may be important to determine if these differences alter the efficacy of artemisinin drugs. Electronic Supplementary Material Supplementary material is available for this article at     

Symptomatic and endoscopic duodenal ulcer relapse rates 12 months following Helicobacter pylori eradication treatment with omeprazole and amoxycillin with or without metronidazole

Aim: To determine the effect of Helicobacter pylori eradication with omeprazole and amoxycillin, with or without metronidazole, on the 12-month course of duodenal ulcer disease. Methods: In a randomized, double-blind study, conducted in 19 hospitals, 105 H. pylori positive duodenal ulcer patients were healed and symptom-free following either omeprazole dual therapy (omeprazole 40 mg o.m.+amoxycillin 500 mg t.d.s., OA, eradication rate 46%, n=52) or omeprazole triple therapy (omeprazole 40 mg o.m.+amoxycillin 500 mg t.d.s.+metronidazole 400 mg t.d.s., OAM, eradication rate 92%, n=53) for 2 weeks, followed by 2 weeks of omeprazole 20 mg o.m. and a 12-month untreated follow-up period, after which time all patients were endoscoped. Endoscopic and symptomatic relapse rates, and effect on H. pylori status measured using ¹³C-urea breath test, were determined. Results: During the 12-month untreated follow-up period, the life-table endoscopic relapse rates were 12% (95% CI: 2–22%) and 2% (95% CI: 0–6%) for OA and OAM patients, respectively. By 12 months, life-table symptomatic relapse rates were 22% (95% CI: 13–37%) and 19% (95% CI: 8–30%) for OA and OAM, respectively. In the 12 months untreated follow-up period, 2/69 (3%, 95% CI: 0–7%) patients rendered H. pylori negative had an endoscopic relapse at the end of the 12-month follow-up period, compared with 5/31 (16%, 95% CI: 3–29%) patients remaining H. pylori positive (P=0.03 between H. pylori positive and negative groups). Twelve of 69 (17%, 95% CI: 8–26%) patients rendered H. pylori negative relapsed symptomatically, compared with 9/31 (29%, 95% CI: 13–45%) patients remaining H. pylori positive (P= N.S. between groups). There was a significant improvement in epigastric pain (P=0.0001), nausea and vomiting (P<0.05) between entry to the study and 1, 6 and 12 months post-treatment for both treatment groups. Conclusions: OAM eradicates H. pylori in significantly more patients than OA, but successful H. pylori eradication with either OAM or OA predisposes to low endoscopic and symptomatic relapse rates for duodenal ulcer patients when followed up for 12 months.     

Temporal trends, risk factors and outcomes in albicans and non-albicans candidaemia: an international epidemiological study in four multidisciplinary intensive care units

This multicentre study (i) evaluated geographic and temporal changes in candidaemia ecology in the critically ill, (ii) identified risk factors associated with non-albicans candidaemia and (iii) examined the association of Candida ecology with mortality. A retrospective cohort study of patients who developed candidaemia in four general Intensive Care Units located in Australia, Greece, Belgium and Brazil was performed. Two hundred Candida organisms were identified by positive blood culture in 189 patients, including 112 Candida albicans (56.0%), 38 Candida glabrata (19.0%), 21 Candida parapsilosis (10.5%), 18 Candida tropicalis (9.0%), 6 Candida krusei (3.0%), 1 Candida famata (0.5%), 1 Candida zeylanoides (0.5%) and 3 non-differentiated Candida spp. (1.5%). No trend towards increased non-albicans species over the study period (P = 0.68) or by geographic area (P = 0.35) was demonstrated. Independent risk factors for non-albicans candidaemia included: female gender [odds ratio (OR) 2.09, 95% confidence interval (CI) 1.13–3.86] and increased central venous catheter days (OR 1.16 per 5-day interval, 95% CI 1.05–1.28). Mortality in the non-albicans group was non-significantly higher than in the albicans group (65% vs. 53%; P = 0.10). This study is unique in that a large number of intensive care candidaemias in four geographically diverse units have been studied.     

昂丹司琼对比托烷司琼预防上腹部分割放疗所致恶心呕吐的临床研究

目的 比较昂丹司琼和托烷司琼预防上腹部分割放疗所致恶心呕吐的有效性与安全性.方法 选择84例接受上腹部分割放疗的肿瘤患者为研究对象,采用随机数字表法分为昂丹司琼组(O组)和托烷司琼组(T组),每组42例.记录两组患者放疗期间恶心呕吐及其他不良反应的发生情况.结果 O组急性期恶心的完全缓解(CR)率显著低于T组(81.0...     

2018—2022年宁德师范学院附属宁德市医院重症医学科患者血流感染病原菌的分布及耐药性分析

目的 分析宁德师范学院附属宁德市医院重症医学科（ICU）患者血流感染病原菌的分布及耐药情况，以指导ICU病原菌的防控及临床合理用药。方法 以2018年1月—2022年12月宁德市医院ICU患者血培养分离病原菌作为研究对象，分析培养出病原菌的分布特点及对药物的耐药情况。结果 共培养出446株病原菌，其中革兰阴性菌203株（45.52%），革兰阳性菌196株（43.95%），真菌45株（10.09%）。检出率最高病原菌依次是凝固酶阴性葡萄球菌、肺炎克雷伯菌、大肠埃希菌、屎肠球菌和金黄色葡萄球菌。肺炎克雷伯菌对哌拉西林耐药率最高，为78.46%，对亚胺培南和美罗培南耐药率为分别为18.46%、20.00%；大肠埃希菌对哌拉西林及环丙沙星耐药率最高，为81.36%、50.85%，对碳青霉烯类抗生素全部敏感；鲍曼不动杆菌对头孢哌酮/舒巴坦和美罗培南耐药率分别为42.86%、50.00%；铜绿假单胞菌对亚胺培南和美罗培南耐药率分别为21.43%、28.57%；凝固酶阴性葡萄球菌对青霉素类抗生素耐药率最高，为94.12%，对阿奇霉素、红霉素及左氧氟沙星耐药率较高，达50.00%以上；金黄色葡萄球菌对青霉素耐药率为100.00%，对万古霉素全部敏感；屎肠球菌对高浓度庆大霉素耐药率为28.00%；粪肠球菌对高浓度庆大霉素耐药率为56.25%。结论 宁德师范学院附属宁德市医院ICU患者血流感染感染病菌种类繁多，以凝固酶阴性葡萄球菌和肺炎克雷伯菌为主。病原菌对药物耐药率较高，应引起临床重视并合理应用抗菌药物。同时加强院内感染的防控工作，减少或延缓耐药株的出现。     

Identification of CYP2D6 impaired functional alleles in Mexican Americans

Objectives To extend the genotyping analysis of the CYP2D6 gene and further explain variability of CYP2D6 activity in Mexican Americans by genetic factors. Methods CYP2D6 gene sequence variations associated with *6, *7, *8, *9, *11, *14, *29, *41, *45, and *46 alleles as well as the 2988G>A SNP were examined in 264 Mexican Americans; 236 had previously been phenotyped with dextromethorphan. All subjects were previously genotyped for CYP2D6*2, *3, *4, *5, *10, *17, and the presence of a gene duplication. Associations between genotype and CYP2D6 activity were determined. Results Mexican Americans revealed a high frequency of functional alleles (CYP2D6*1 and *2; 73.1%), followed by CYP2D6*4 (non-functional, 10.0%) and the reduced-function allele *41 (9.5%). The frequencies of CYP2D6*5, *6, *9, *10, duplication, and 2988A were 1.7%, 0.4%, 1.1%, 2.8%, 0.8%, and 5.7%, respectively. CYP2D6*3, *17, and *29 were found only in one individual (CYP2D6*2/*3, *1/*17, and *4/*29), while CYP2D6*7, *8, *11, *14, *45, and *46 were absent in this study population. Decreased CYP2D6 activity was more accurately predicted by the presence *41[−1584C] compared to *41[2988A]. One genotype/phenotype discordant subject was resolved by the presence of a CYP2D6*6 allele (*4/*6), while two other cases remained discordant (*41/*41 and *1/*1). Conclusions The CYP2D6*4, *5, and *6 null alleles along the reduced function alleles *9, *10, and *41 are the major cause for diminished dextromethorphan oxidative capacity in Mexican Americans. These findings may have implications for the safety and efficacy of CYP2D6 substrates taken by Mexican Americans.     

Inhibition of crown-gall tumorigenesis with plant extracts

Measurement of the inhibition of crown-gall tumors on potato discs is an antitumor bioassay method for detection of anti-tumor compounds from higher plants. In this study, after surface sterilization, tuber discs were co-cultivated with Agrobacterium tumefaciens B₆S₃ for two days. The discs were then inoculated on MS media with the crude extracts obtained from different parts of various plants – Allium sativum L. (Liliaceae), Salvia verbenaca L., Rosmarinus officinalis L., Ocimum basiculum L., Lavandula stoechas L. (Lamiaceae), Althaea cannabina L. (Malvaceae), Petroselinum sativum Mill. (Apiaceae), Pelargonium radicula L. (Geraniaceaea), Juglans regia L. (Juglandaceae), Platanus orientalis L. (Platanaceae), Laurus nobilis L. (Lauraceae), Ranunculus ficaria L. (Ranunculaceae), and Abies equi-trojani Aschers. et Sint. Ex Boiss (Pinaceae). Tumors appeared after 10-15 days, and tumor inhibition was detected only in six plant extracts of 13 (A. sativum, R. officinalis, P. orientalis, L. nobilis, R. ficaria, and A. equi-trojani) when compared to control material. Constitutive tumor inhibition activities were higher in these plant extracts (63.5%, 56.1%, 61.7%, 54.6%, 69.7%, and 57.9% at 0 min; 58.8%, 54.6%, 58.8%, 48.4%, 62.6%, and 51.6% for 15?min after bacterial inoculation).     

Use of a semi-physiological pharmacokinetic model to investigate the influence of itraconazole on tacrolimus absorption,distribution and metabolism in mice

1.?The aim of this study was to investigate the influence of itraconazole (ITCZ) on tacrolimus absorption, distribution and metabolism by developing a semi-physiological pharmacokinetic model of tacrolimus in mice.

2.?Mice were randomly divided into four groups, namely control group (CG, taking 3?mg kg^?1 tacrolimus only), low-dose group (LDG, taking tacrolimus with 12.5?mg kg^?1 ITCZ), medium-dose group (MDG, taking tacrolimus with 25?mg kg^?1 ITCZ) and high-dose group (HDG, taking tacrolimus with 50?mg kg^?1 ITCZ).

3.?Liver clearance (CL_li) decreased significantly (**p?<?0.01) in LDG (35.3%), MDG (45.2%) and HDG (58.7%) mice compared to CG mice. With respect to gut clearance (CL_gu), significant (**p?<?0.01) decrease was also revealed in LDG (35.9%), MDG (50.2%) and HDG (64.6%) mice. A significant (**p?<?0.01) higher tacrolimus brain-to-blood partition coefficient (K_t,br) was found in MDG (25.3%) and HDG (55.9%) mice than in CG mice. Moreover, a significant (*p?<?0.05) increase (16.3%) was found in the absorption rate constant (K_a) in HDG mice compared to CG mice. There was a significant (**p?<?0.01) association between ITCZ dose and the change in CL_gu (ΔCL_gu, r=??0.790), the change in CL_li (ΔCL_li, r=??0.787) and the change in K_t,br (ΔK_t,br, r?=?0.727), while the association between ITCZ dose and the change in K_a (ΔK_a) was not significant (p?>?0.05).

4.?These findings could be useful in predicting the efficacy and toxicity of tacrolimus, and drug–drug interaction of ITCZ and tarcolimus in human.     

The efficacy of tadalafil in improving sexual satisfaction and overall satisfaction in men with mild,moderate, and severe erectile dysfunction: a retrospective pooled analysis of data from randomized,placebo-controlled clinical trials

ABSTRACT

Background: Satisfaction with the sexual experience is considered important when evaluating the impact of treatments for erectile dysfunction (ED), yet satisfaction has been infrequently assessed in clinical trials.

Objective: To evaluate satisfaction with, and enjoyment of, the sexual experience in men with ED enrolled in 11 placebo-controlled clinical trials of tadalafil.

Study design and methods: Retrospective pooled analysis of data from 11 randomized, double blind, placebo-controlled clinical trials of tadalafil. Men with mild (N = 838), moderate (N = 558), or severe (N = 703) ED who were randomized to tadalafil 10?mg or 20?mg or placebo taken as needed for 12 weeks were included in this analysis. Efficacy measures included the International Index of Erectile Function (IIEF). Reported herein are the scores on the IIEF overall satisfaction domain and individual IIEF questions (IIEF‐Q7, satisfaction with intercourse; and IIEF‐Q8, enjoyment of intercourse).

Results: At least moderate satisfaction (IIEF overall satisfaction domain) was reported by 55% and 72% of patients with mild ED taking tadalafil 10?mg and 20?mg, respectively, compared with 33% taking placebo (?p < 0.002); 60% and 65% vs. 19% of patients with moderate ED (?p < 0.001); and 32% and 49% vs. 9% with severe ED (?p < 0.001). Satisfactory intercourse during most attempts or almost always/always (IIEF‐Q7) was reported by 59% and 79% of patients with mild ED taking tadalafil 10?mg and 20?mg vs. 32% taking placebo (?p < 0.001); 52% and 65% vs. 18% with moderate ED (?p < 0.001); and 28% and 49% vs. 5% with severe ED (?p < 0.001). Highly or very highly enjoyable intercourse (IIEF‐Q8) was reported by 45% and 63% of patients with mild ED taking tadalafil 10?mg and 20?mg vs. 21% taking placebo (?p < 0.001); 43% and 56% vs. 16% with moderate ED (?p < 0.001); and 19% and 44% vs. 5% with severe ED (?p < 0.001).

Conclusions: Compared with placebo, tadalafil 10?mg and 20?mg improved overall satisfaction with the sexual experience, intercourse satisfaction, and intercourse enjoyment in men with mild, moderate, and severe ED.     

Investigation of the prevalence of tetQ, tetX and tetX1 genes in Bacteroides strains with elevated tigecycline minimum inhibitory concentrations

In this study, the antibiotic susceptibilities to tigecycline and tetracycline of 35 selected Bacteroides fragilis group strains were determined by Etest, and the presence of tetQ, tetX, tetX1 and ermF genes was investigated by polymerase chain reaction (PCR). tetQ was detected in all 12 B. fragilis group isolates (100%) exhibiting elevated tigecycline minimum inhibitory concentrations (MICs) (≥8 μg/mL) as well as the 8 strains (100%) with a tigecycline MIC of 4 μg/mL, whilst tetX and tetX1 were present in 15% and 75% of these strains, respectively. All of these strains were fully resistant to tetracycline (MIC ≥ 16 μg/mL). On the other hand, amongst the group of strains with tigecycline MICs < 4 μg/mL (15 isolates), tetQ, tetX and tetX1 were found less frequently (73.3%, 13.3% and 46.7%, respectively). All but two strains harbouring the tetQ gene in this group were non-susceptible to tetracycline, with a MIC > 4 μg/mL. These data suggest that in most cases tigecycline overcomes the tetracycline resistance mechanisms frequently observed in Bacteroides strains. However, the presence of tetX and tetX1 genes in some of the strains exhibiting elevated MICs for tigecycline draws attention to the possible development and spread of resistance to this antibiotic agent amongst Bacteroides strains. The common occurrence of ermF, tetX, tetX1 and tetQ genes together predicted the presence of the CTnDOT-like Bacteroides conjugative transposon in this collection of Bacteroides strains.     

Chemical composition,antimicrobial, and cytotoxicity studies on S. erianthum and S. macranthum essential oils

Context: Solanum erianthum D. Don and Solanum macranthum Dunal (Solanaceae) are widely used in traditional medicine. The leaves act as an abortifacient and in particular to treat leucorrhoea, sores, and skin irritations.

Objective: This study was undertaken to characterize the volatile constituents of the leaf and fruit essential oils of S. erianthum and S. macranthum; their antimicrobial and in vitro cytotoxic bioassay against human breast and prostate tumor cells.

Methods: The volatile oils were obtained by hydrodistillation and analyzed for their constituents by gas chromatography-mass spectrometry (GC-MS). Minimum Inhibitory Concentrations (MIC) were determined using the microbroth dilution technique while the cytotoxic potentials were evaluated using the Cell Titre 96^(R) AQ_ueous Non-Radioactive Cell Proliferation Assay method.

Results: Solanum erianthum essential oils were characterized by the abundance of α-terpinolene (17.8%), α-phellandrene (17.5%), p-cymene (15.7%) and β-pinene (11.7%) in the leaves; α-humulene (23.1%), humulene epoxide II (20.0%), caryophyllene oxide (16.5%), methyl salicylate (11.8%) and β-caryophyllene (10.9%) in the fruits. The leaf oil of S. macranthum consisted of (E)-phytol (29.0%), pentadecanal (28.1%) and pentadecane (7.7%) while the major fruit oil constituents were α-humulene (36.5%), β-caryophyllene (17.8%), ethyl palmitate (9.4%), and methyl salicylate (8.2%). Solanum erianthum leaf volatile oil demonstrated potent inhibitory activity against Hs 578T and PC-3 human breast and prostate tumor cells respectively. In addition, the Solanum essential oils exhibited significant antimicrobial activity (19.5–625 µg/mL) on pathogens employed in the assay.

Conclusion: The Solanum essential oils possess strong antimicrobial activity in addition to the potent cytotoxic potential of S. erianthum leaf oil against Hs 578T and PC-3 cells.     

Detection of lfrA and tap efflux pump genes among clinical isolates of non-pigmented rapidly growing mycobacteria

This study was performed to detect LfrA and Tap efflux pumps among clinical isolates of non-pigmented rapidly growing mycobacteria (NPRGM). Gene detection was performed using polymerase chain reaction (PCR) with specific primers designed for each gene. Susceptibility of the strains to doxycycline, tigecycline and ciprofloxacin was analysed using the broth microdilution reference technique. In total, 166 clinical isolates were included in the study. The lfrA gene was detected in four strains (2.4%), comprising two strains of Mycobacterium chelonae (6.7% of this species), one Mycobacterium fortuitum (1.1%) and one Mycobacterium mucogenicum (14.3%). The tap gene was detected in 109 strains (65.7%), comprising 3 Mycobacterium abscessus (33.3%), 12 M. chelonae (40%), 75 M. fortuitum (84.3%), 2 Mycobacterium mageritense (40%), 15 Mycobacterium peregrinum (68.2%), 1 Mycobacterium alvei and 1 Mycobacterium porcinum; no strains of M. mucogenicum were tap-positive. No differences between tap-positive and -negative strains were observed for resistance to doxycycline (Fisher's exact test, P = 0.055). lfrA is rare among clinical isolates of NPRGM, whilst tap is found more commonly. No correlation was detected between the presence of the efflux pumps and resistance to quinolones or tetracyclines.     

2018—2021年武汉大学人民医院儿童血流感染的病原菌分布特征及耐药性分析

目的 分析武汉大学人民医院儿童血流感染病原菌特征及耐药性分析。方法 选取2018年1月—2021年12月武汉大学人民医院患儿血培养标本分离的病原菌及其药物敏感性数据进行统计分析。结果 共收集到21 571份住院儿童的血培养标本,共分离出病原菌1 646株,检测阳性率为7.63%。其中革兰阳性菌910株,占比为55.29%,革兰阴性菌715株,占比43.44%,真菌21株,占比1.28%。儿童血流感染前5位的病原菌依次为肺炎克雷伯菌、表皮葡萄球菌、肺炎链球菌、人葡萄球菌和大肠埃希菌,占比分别为20.60%、15.25%、14.52%、10.69%、10.57%。耐甲氧西林的凝固酶阴性葡萄球菌（MRCNS）检出率为20.47%,未发现有万古霉素耐药的凝固酶阴性葡萄球菌。肺炎克雷伯菌产超广谱β-内酰胺酶（ESBL）阳性占比为74.93%,大肠埃希菌ESBL阳性占比为6.90%;耐碳青霉烯酶的肠杆菌目（CRE）大肠埃希菌占比为56.32%,CRE肺炎克雷伯菌占比为0%。肺炎链球菌对红霉素、克林霉素、四环素耐药率较高,分别为100.0%、92.9%、85.2%,未发现对莫西沙星、利奈唑胺以及万古...     

Recalculation of cardiovascular risk score as a surrogate marker of change in clinical care of diabetes patients: the Alphabet POEM project (Practice Of Evidence-based Medicine)

SUMMARY

Aims: To assess the impact of evidence-based strategies on the care of subjects with diabetes, in particular on their coronary heart disease (CHD) risk, using the Alphabet Strategy template and coronary heart disease (CHD) risk calculators as novel audit tools.

Methods: Diabetes and cardiovascular parameters were collected on 400 consecutive type 2 diabetes patients attending the outpatient clinic. The subjects were men and women aged 21-75 years with necessary follow-up data from referral or first chronological available letter in the notes (T0) to the most recent follow-up visit (Tfu). The average follow-up period was 5 years. Absolute CHD risk was calculated using the Framingham risk function and the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. The results were analysed using Student's paired t-test and chi-squared test.

Results (T0 vs.Tfu): Advice: smoking status improved 18.3 vs. 15.5%: p?=?0.3. Blood pressure: systolic blood pressure improved 145.8?±?21.1 vs. 140.1?±?20.5mmHg: p?<?0.0001. Diastolic blood pressure improved 82.0?±?12.2 vs. 76.5?±?11.0mmHg: p?<?0.0001. Cholesterol: total cholesterol improved 5.8?±?1.6 vs. 4.9?±?1.0 mmol/L: p?<?0.0001; high density lipoprotein (HDL) cholesterol improved 1.05 vs. 1.26 mmol/L: p?<?0.001. Diabetes control: glycated haemoglobin (HbA1c)% worsened 7.9?±?1.8 vs. 8.1?±?1.5: p?<?0.0001. However, when adjusted for duration of diabetes, this improved non-significantly by 12% overall. Eye examination: improved 86.5 vs. 97.5%: p?<?0.001. Feet examination: improved 69.8 vs. 83.5%: p?<?0.001. Guardian drugs: significantly more patients were on aspirin (29.0 vs. 83.5%: p?<?0.001), angiotensin converting enzyme (ACE) inhibitors (32.0 vs. 64.5%: p?<?0.001), and lipid lowering therapy (16.8 vs. 55.0%: p?<?0.001). Heart disease risk scores: a significant reduction in Framingham 10-year absolute cardiac risk was achieved (20.6?±?10.04% vs. 16.7?±?9.1%: p?=?0.001). Using the UKPDS risk engine, there was a non-significant reduction in absolute CHD risk over the follow-up period (23.8?±?14.8% vs. 23.7?±?15.5: p?=?NS). There were significant improvements between age-adjusted risk score (Tadj) and follow-up values (Tfu) (Framingham: 23.67% (Tadj) vs. 16.7% (Tfu); UKPDS 31.2% (Tadj) vs. 23.7% (Tfu)). For UKPDS stroke risk, a significant improvement was seen from Tadj to Tfu (19.0% (Tadj) vs. 16.4% (Tfu): p?<?0.001), with a significant deterioration noted between T0 and Tfu (11.5% (T0) vs. 16.4% (Tfu): p?<?0.0001).

Conclusions:The Alphabet Strategy is a novel evidence-based approach to clinical diabetes care, which produced a statistically significant improvement in most of the assessed parameters. The Alphabet Practice Of Evidence-based Medicine (POEM) template is a useful clinical tool for diabetes care and audit. It includes most of the components of diabetes audit required by the National Service Framework (NSF) and the United Kingdom GP contract.     

2015—2017年福州市第二医院铜绿假单胞菌的分布及耐药性分析

目的 分析2015—2017年福州市第二医院铜绿假单胞菌的分布及耐药性,为临床合理使用抗菌药物提供参考。方法 收集福州市第二医院2015—2017年临床分离的943株铜绿假单胞菌,对其标本来源分布、科室分布和耐药性进行分析。结果 共分离出943株铜绿假单胞菌,下呼吸道标本和伤口分泌物分别占50.2%、35.6%;科室分布以骨科（29.5%）最多,其次为呼吸内科（13.8%）和ICU（10.8%）。各年耐药率、菌株分离率总体呈下降趋势。铜绿假单胞菌对氨曲南的耐药率最高,达25.7%,对亚胺培南和美洛培南的耐药率分别为13.9%、9.1%,对阿米卡星的耐药率最低,为2.1%。骨科铜绿假单胞菌对亚胺培南（2.5%）和美洛培南（1.8%）仍然十分敏感。但呼吸内科和ICU的铜绿假单胞菌对亚胺培南和美罗培南的耐药率已经高达30%、20%。结论 应加强细菌耐药监测,采取有效措施控制耐药菌株传播,对延缓泛耐药铜绿假单胞菌的出现和防止水平传播将起到重要作用。