BACKGROUND: Healthcare professionals have a duty to maintain basic life support(BLS) skills. This study aims to evaluate medical students' factual knowledge of BLS and the training they receive.METHODS: A cross-se...BACKGROUND: Healthcare professionals have a duty to maintain basic life support(BLS) skills. This study aims to evaluate medical students' factual knowledge of BLS and the training they receive.METHODS: A cross-sectional, closed-response questionnaire was distributed to the fi rst-and fourth-year students studying at institutions in the United Kingdom. The paper questionnaire sought to quantify respondent's previous BLS training, factual knowledge of the BLS algorithm using five multiple choice questions(MCQs), and valuate their desire for further BLS training. Students received 1 point for each correctly identifi ed answer to the 5 MCQ's.RESULTS: A total of 3,732 complete responses were received from 21 medical schools. Eighty percent(n=2,999) of students completed a BLS course as part of their undergraduate medical studies. There was a signifi cant difference(P<0.001) in the percentage of the fourth-year students selecting the correct answer in all the MCQ's compared to the fi rst-year students except in identifyingthe correct depth of compressions required during CPR(P=0.095). Overall 10.3%(95% CI 9.9% to 10.7%) of respondents correctly identified the answer to 5 MCQ's on BLS: 9% of the first-year students(n=194) and 12% of the fourth-year students(n=190). On an institutional level the proportion of students answering all MCQ's correctly ranged from 2% to 54% at different universities. Eighty-one percent of students(n=3,031) wished for more BLS training in their curriculum.CONCLUSION: Factual knowledge of BLS is poor among medical students in the UK. There is a disparity in standards of knowledge across institutions and respondents indicating that they would like more training.展开更多
目的:考察精神疾病病耻感量表中文版(Stigma Scale for Mental Illness,SSMI-C)的信度和效度。方法:方便选取339名门诊和住院精神分裂症患者,用其中172名进行探索性因素分析,其余167名进行验证性因素分析。间隔2周后,随机抽取其中101名...目的:考察精神疾病病耻感量表中文版(Stigma Scale for Mental Illness,SSMI-C)的信度和效度。方法:方便选取339名门诊和住院精神分裂症患者,用其中172名进行探索性因素分析,其余167名进行验证性因素分析。间隔2周后,随机抽取其中101名患者进行重测,评定重测信度。以自编精神疾病患者病耻感面谈提纲(Stigma Interview for Mental Illness,SIMI)及罗森伯格自尊量表(Rosenberg Self-Esteem Scale,SES)为效标关联效度。结果:(1)探索性因素分析中设定3个因子,解释变异量的39.3%,除第6条目外,将个别项目根据结果调整后,各条目的因子载荷均在0.415~0.791之间。验证性分析指标GFI=0.89、NNFI=0.92、CFI=0.94、χ2/df=1.81、REMEA=0.07。SSMI-C与SIMI及罗森伯格自尊量表得分相关(r=0.78,-0.40,均P<0.01)。(2)SSMI-C的Cronbachα系数为0.82(P<0.01),重测相关系数为0.75(P<0.01)。总分与各因子的相关系数在0.48~0.83之间,各因子间的相关系数在0.12~0.34之间。结论:精神疾病病耻感量表中文版的信度和效标关联效度均较理想,结构效度在分析调整后也较理想,符合心理测量学要求,可以用于国内精神分裂症患者病耻感的研究。展开更多
AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis(NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH.METHODS: Th...AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis(NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH.METHODS: This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome(Met S) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients receivedlifestyle advice and were treated for a 12 mo period with rosuvastatin(10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid(SUA), high sensitivity C reactive protein(hs CRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values.RESULTS: The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20 th, which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3rd treatment month(ANOVA P < 0.001), while alkaline phosphatase activities by the 6th treatment month(ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced(P < 0.001). Lipid values were normalised by the 3rd treatment month. No patient had Met S by the 9th treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group.CONCLUSION: These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve Met S within 12 mo. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies.展开更多
AIM: To investigate the bactericidal and anti-adhesive properties of 25 plants against Helicobacter pylori (H pylori).METHODS: Twenty-five plants were boiled in water to produce aqueous extracts that simulate the effe...AIM: To investigate the bactericidal and anti-adhesive properties of 25 plants against Helicobacter pylori (H pylori).METHODS: Twenty-five plants were boiled in water to produce aqueous extracts that simulate the effect of cooking. The bactericidal activity of the extracts was assessed by a standard kill-curve with seven strains of H pylori. The anti-adhesive property was assessed by the inhibition of binding of four strains of FITC-labeled H pylori to stomach sections. RESULTS: Of all the plants tested, eight plants, including Bengal quince, nightshade, garlic, dill, black pepper, coriander, fenugreek and black tea, were found to have no bactericidal effect on any of the isolates. Columbo weed, long pepper, parsley, tarragon, nutmeg, yellow-berried nightshade, threadstem carpetweed, sage and cinnamon had bactericidal activities against H pylori, but total inhibition of growth was not achieved in this study. Among the plants that killed H pylori, turmeric was the most efficient, followed by cumin, ginger, chilli, borage, black caraway, oregano and liquorice. Moreover, extracts of turmeric; borage and parsley were able to inhibit the adhesion of H pylori strains to the stomach sections.CONCLUSION: Several plants that were tested in our study had bactericidal and/or anti-adhesive effects on H pylori. Ingestion of the plants with anti-adhesive properties could therefore provide a potent alternative therapy for H pylori infection, which overcomes the problem of resistance associated with current antibiotic treatment.展开更多
During liver resection surgery for cancer or liver transplantation,the liver is subject to ischaemia (reduction in blood flow) followed by reperfusion (restoration of blood flow),which results in liver injury [ischemi...During liver resection surgery for cancer or liver transplantation,the liver is subject to ischaemia (reduction in blood flow) followed by reperfusion (restoration of blood flow),which results in liver injury [ischemiareperfusion (IR) or IR injury]. Modulation of IR injury can be achieved in various ways. These include hypothermia,ischaemic preconditioning (IPC) (brief cycles of ischaemia followed by reperfusion of the organ before the prolonged period of ischaemia i.e. a conditioning response),ischaemic postconditioning (conditioning after the prolonged period of ischaemia but before the reperfusion),pharmacological agents to decrease IR injury,genetic modulation of IR injury,and machine perfusion (pulsatile perfusion). Hypothermia decreases the metabolic functions and the oxygen consumption of organs. Static cold storage in University of Wisconsin solution reduces IR injury and has prolonged organ storage and improved the function of transplanted grafts. There is currently no evidence for any clinical advantage in the use of alternate solutions for static cold storage. Although experimental data from animal models suggest that IPC,ischaemic postconditioning,various pharma-cological agents,gene therapy,and machine perfusion decrease IR injury,none of these interventions can be recommended in clinical practice. This is because of the lack of randomized controlled trials assessing the safety and efficacy of ischaemic postconditioning,gene therapy,and machine perfusion. Randomized controlled trials and systematic reviews of randomized controlled trials assessing the safety and efficacy of IPC and various pharmacological agents have demonstrated biochemical or histological improvements but this has not translated to clinical benefit. Further well designed randomized controlled trials are necessary to assess the various new protective strategies in liver resection.展开更多
The importance of nitric oxide(NO) in vascular physiology is irrefutable;it stimulates the intracellular production of cyclic guanosine monophosphate(cGMP),initiating vascular smooth muscle relaxation.This biochemical...The importance of nitric oxide(NO) in vascular physiology is irrefutable;it stimulates the intracellular production of cyclic guanosine monophosphate(cGMP),initiating vascular smooth muscle relaxation.This biochemical process increases the diameter of small arteries,regulating blood flow distribution between arterioles and the microvasculature.The kidney is no exception,since NO predominantly dilates the glomerular afferent arterioles.It is now evident that the vascular production of cGMP can be augmented by inhibitors of phosphodiesterase type 5(PDE 5),the enzyme which breakdowns this cyclic nucleotide.This has clinical relevance,since diabetic nephropathy(DN) a major microvascular complication of diabetes mellitus and the most common cause of end-stage renal disease,increases intraglomerular capillary pressure,leading to glomerular hypertension.PDE 5 inhibitors may have,therefore,the potential to reduce glomerular hypertension.This review describes the use of PDE 5 inhibitors to improve the metabolic,haemodynamic and inflammatory pathways/responses,all of which are dysfunctional in DN.展开更多
Context: Stable angina pectoris in women has often been considered a “soft”d iagnosis, with less-severe prognostic implications than in men, but large-scal e population studies are lacking. Objective: To determine s...Context: Stable angina pectoris in women has often been considered a “soft”d iagnosis, with less-severe prognostic implications than in men, but large-scal e population studies are lacking. Objective: To determine sex differences in the incidence and prognosis of stable angina in a large ambulatory population. Desi gn: Prospective cohort study using linked national registers. Setting: All munic ipal primary health care centers, hospital outpatient clinics, occupational heal th care services, and the private sector in Finland. Participants: Among ambulat ory patients aged 45 to 89 years who had no history of coronary disease, we defi ned new cases of “nitrate angina”based on nitrate prescription(56 441 women an d 34 885 men) or “test-positive angina”based on abnormal invasive or noninvas ive test results(11 391 women and 15 806 men). Potentially eligible patients wer e evaluated between January 1, 1996, and December 31, 1998. Follow-up ended in December 2001. Main Outcome Measures: Coronary mortality at 4 years(n=7906 death s) and fatal and nonfatal myocardial infarction at 1 year(n=3129 events). Results: The age-standardized annual incidence per 100 population of all cases of ang ina was 2.03 in men and 1.89 in women, with a sex ratio of 1.07(95%confidence i nterval[CI], 1.06-1.09). At every age, nitrate angina in women and men was asso ciated with a similar increase in risk of coronary mortality relative to the gen eral population. Women with test-positive angina who were younger than 75 years had higher coronary-standardized mortality ratios than men; for example, among those aged 55 to 64 years, it was 4.69(95%CI, 3.60-6.11) in women compared wi th 2.40(95%CI, 2.11-2.73) in men(P< .001 for interaction). There was a strong, graded relationship between amount of nitrates used and event rates; women usin g higher doses of nitrates had prognoses comparable with those of men. Among pat ients with diabetes and test-positive angina, age-standardized coronary event rates were 9.9 per 100 person-years in women vs 9.3 in men(P=.69), and the full y adjusted male-female sex ratio was 1.07(95%CI, 0.81-1.41). Conclusions: Wom en have a similarly high incidence of stable angina compared with men. Furthermo re, stable angina in women is associated with increased coronary mortality relat ive to women in the general population and, among easily identifiable clinical s ubgroups, has similarly high absolute rates of prognostic outcomes compared with men.展开更多
Significant concerns over the health,social and economic burdens of the two most common,and frequently co-misused drugs of abuse,alcohol and tobacco,has encouraged focused but separate health promotion and disease pre...Significant concerns over the health,social and economic burdens of the two most common,and frequently co-misused drugs of abuse,alcohol and tobacco,has encouraged focused but separate health promotion and disease prevention policies.However,this separation of focus means that while individuals who present with alcohol-related problems are increasingly supported to attain and maintain abstinence from alcohol they are not routinely assisted to refrain from smoking.This is tragically inopportune as alcohol and tobacco have an established"synergistic"effect on aerodigestive cancer risk.Moreover,even when patients successfully tackle their alcohol problems they remain at increased risk for developing these cancers,especially if they continue to smoke.A case series is presented together with a discussion on how service provision for co-misuse could be improved to obviate aerodigestive cancer risk.Given the prevalence of alcohol and tobacco use in the United Kingdom,these observations may have far reaching implications for the individual,health provider(s)and wider society.展开更多
Objective To investigate the role of acyl-coenzyme A:cholesterol acyltransferase inhibitor(ACATI) in apoptosis induced by lipids and whether lipids-induced apoptosis is accompanied by increase of free cholesterol in e...Objective To investigate the role of acyl-coenzyme A:cholesterol acyltransferase inhibitor(ACATI) in apoptosis induced by lipids and whether lipids-induced apoptosis is accompanied by increase of free cholesterol in endoplasmic reticulum(ER),in order to further understand the mechanism of lipids-induced apoptosis in advanced atherosclerosis.Methods Human vascular smooth muscle cells(VSMCs) and phorbol 12-myristate 13-acetate(PMA) differentiated THP-1 macrophages were used.Tritiated thymidine incorporation was applied to detect cell proliferation.Cytotoxicity was assessed by lactate dehydrogenase(LDH) release.4',6-diamidino-2-phenylindole(DAPI) staining,caspase-3,-7 assay,and Annexin-V/propidium iodide(PI) staining were used to detect apoptosis.High performance liquid chromatography was used in intracellular free cholesterol and cholesterol ester assay.ER free cholesterol was quantified.Results Different lipids had different effects on proliferation and cytotoxicity of VSMCs.25-hydroxycholesterol(25OHC) had biphasic effects on the proliferation of VSMCs.At low concentration,it stimulated cell proliferation,but turned to proliferation inhibition as concentration reached 15 μg/mL.25OHC and acetylated low density lipoprotein(AcLDL) could respectively induce apoptosis in human VSMCs and PMA differentiated THP-1 macrophages,which was aggravated by ACATI,accompanied by increase of intracellular free cholesterol content.There was also an increase of cholesterol content in ER with AcLDL-induced apoptosis in THP-1 macrophages.Conclusions Lipids could induce apoptosis,accompanied by increase of intracellular free cholesterol content,which could be augmented by ACATI,suggesting that insults resulting in ER free cholesterol rise might be the initiator of apoptosis.展开更多
Letters to the editor can provide useful scientific information and evaluation of published work as well as acting as an additional level of peer review.Furthermore,letters are good reading material,especially if they...Letters to the editor can provide useful scientific information and evaluation of published work as well as acting as an additional level of peer review.Furthermore,letters are good reading material,especially if they involve a debate between authors.Finally,letters are relatively short.Therefore,inexperienced career researchers can use such an opportunity to practice putting together a cogent argument.However,it is far from an ideal situation if letters are the only(or main)type of article on which to base an academic career.展开更多
Objectives: Antiretroviral therapy (ART) has been associated with lipodystrophy in children. We evaluated changes in various anthropometric measurements for the assessment of lipodystrophy and assessed whether there w...Objectives: Antiretroviral therapy (ART) has been associated with lipodystrophy in children. We evaluated changes in various anthropometric measurements for the assessment of lipodystrophy and assessed whether there was an association with use of protease inhibitors (PI), non-PI containing ART and/or stavudine (d4T). Methods: Eighty-five HIV-infected children attending the HIV clinic at Great Ormond Street Hospital (GOSH) were included. The average follow-up was 8.4 months (range 3 - 12 months). Body fat redistribution was assessed by anthropometric measurements including skinfold thickness and circumferences of upper and lower limbs. Measurements were converted to age- and sex-adjusted z-scores through development stages including puberty. Results: Sixty children had taken ART;37 received PI-containing;38 received d4T;25 had never been treated. In the studied population, clinically important changes with decreases in biceps (BSF), subscapular skinfolds and total body fat (4SFT) over period of 12 months were observed. Some increase was noticed in triceps skinfolds (TSF). Limbs circumferences remained at the same level. Further we looked at 4 months basis changes in anthropometric measurements stratified by baseline ART. Generally z-scores of anthropometric measurements were lower in therapy naive children when compared to ART groups. PI-based ART regimens resulted in significant increases in BSF with a trend towards increases in TSF, suprailiac and 4SFT. Mid-arm and thigh circumferences were higher in PI compared to naive group. Similarly, significant changes in BSF z-scores were associated with d4T use. Increases were seen in TSF and mid-arm circumference and decreases were observed in subscapular skinfolds and calf circumference z-scores. Conclusions: Body fat redistribution in HIV-infected children with sub-clinical lipodystrophy could be detected by anthropometric measurements, particularly when PI or d4T is included in ART. Over time, changes with increase in arm and trunk fat, and no change or decrease in leg fat were more pronounced among ART-receiving children.展开更多
Introduction In my presentation to the 4th International Symposium on Hepatic Failure and Artificial Liver Support in Chongqing on which this paper is based, I was specifically asked to address the question of whether...Introduction In my presentation to the 4th International Symposium on Hepatic Failure and Artificial Liver Support in Chongqing on which this paper is based, I was specifically asked to address the question of whether albumin dialysis, as in the Molecular Adsorbents Recirculating System (MARS) did correct known abnormalities of the disturbed pathophysiology in liver failure. Before doing this展开更多
目的明确广西隆安县队列HBsAg无症状携带者感染的乙型肝炎病毒(hepatitis B virus,HBV)准种序列长期演化特征。方法收集9名广西隆安县队列HBsAg无症状携带者2004年、2007年、2013年、2019年或2020年4个不同时间点血清样本。酶联免疫吸...目的明确广西隆安县队列HBsAg无症状携带者感染的乙型肝炎病毒(hepatitis B virus,HBV)准种序列长期演化特征。方法收集9名广西隆安县队列HBsAg无症状携带者2004年、2007年、2013年、2019年或2020年4个不同时间点血清样本。酶联免疫吸附测定法检测HBV血清学标志物;聚合酶链式反应(polymerase chain reaction,PCR)荧光探针法检测HBV病毒载量;试剂盒提取HBV DNA;PCR法扩增HBV全基因组,进行二代测序;利用Mega等软件对所获得的序列进行生物信息学分析。结果共获得23份血清样本,309条全长基因准种序列,每份标本平均获得(0.18±0.07)G测序数据量。55.55%(5/9)的研究对象携带的HBV毒株基因型在长期进化过程中发生了基因型转换,PreS/S区系统进化树基因分型结果与全基因组分析结果完全一致;发现B/C、I/C重组体;各研究标本的Sn值范围为0~0.37,D值范围为0~0.11;共检出21种特殊单核苷酸/氨基酸突变位点(S区7种,X区2种,PreC区3种,BCP区9种)和6种缺失突变,发现多联突变组合形式,未发现任何耐药突变,77.8%(7/9)研究对象在2004年携带的HBV毒株发生了BCP区nt1762(A→T)/1764(G→A)双突变和PreC区1896位(G→A)点突变,HBV基因可在无抗病毒药物压力下由突变型可恢复为野生型和(或)野生型转变为突变型;HBV基因组进化率为2.03×10^(-5)~3.50×10^(-3)。结论在HBV自然感染进程中,HBV基因型和重组体、准种复杂性和多样性可随时间发生改变;HBV基因突变型和野生型可相互转换,一定程度上降低了利用基因型和相关突变来预测临床结局的价值;隆安县乙型肝炎表面抗原(hepatitis B surface antigen,HBsAg)无症状携带者HBV基因组进化率很高。展开更多
Background Podocyte apoptosis is recently indicated as an early phenomenon of diabetic nephropathy. Pancreatic β-cells exposed to saturated free fatty acid palmitate undergo irreversible endoplasmic reticulum (ER) ...Background Podocyte apoptosis is recently indicated as an early phenomenon of diabetic nephropathy. Pancreatic β-cells exposed to saturated free fatty acid palmitate undergo irreversible endoplasmic reticulum (ER) stress and consequent apoptosis, contributing to the onset of diabetes. We hypothesized that palmitate could induce podocyte apoptosis via ER stress, which initiates or aggravates proteinuria in diabetic nephropathy. Methods Podocyte apoptosis was detected by 4',6-diamidio-2-phenylindole (DAPI) stained apoptotic cell count and Annexin V-PI stain. The expressions of ER molecule chaperone glucose-regulated protein 78 (GRP78), indicators of ER-associated apoptosis C/EBP homologous protein (CHOP), and Bcl-2 were assayed by Western blotting and real-time PCR. GRP78 and synaptopodin were co-localized by immunofluorescence stain. Results Palmitate significantly increased the percentage of cultured apoptotic murine podocytes time-dependently when loading 0.75 mmol/L (10 hours, 13 hours, and 15 hours compared with 0 hour, P 〈0.001) and dose-dependently when loading palmitate ranging from 0.25 to 1.00 mmol/L for 15 hours (compared to control, P 〈0.001). Palmitate time-dependently and dose-dependently increased the protein expression of GRP78 and CHOP, and decreased that of Bcl-2. Palmitate loading ranging from 0.5 to 1.0 mmol/L for 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to control (P 〈0.001), with the maximum concentration being 0.75 mmol/L. Palmitate 0.5 mmol/L loading for 3 hours, 8 hours, and 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to 0 hour (P 〈0.001), with the maximum effect at 3 hours. Confocal microscopy demonstrated that GRP78 expression was significantly increased when exposed to 0.5 mmol/L of palmitate for 8 hours compared to control. Conclusion Palmitate could induce podocyte apoptosis via ER stress, suggesting podocyte apoptosis and consequent proteinuria caused by lipotoxic free fatty acid could be ameliorated by relief of ER stress.展开更多
文摘BACKGROUND: Healthcare professionals have a duty to maintain basic life support(BLS) skills. This study aims to evaluate medical students' factual knowledge of BLS and the training they receive.METHODS: A cross-sectional, closed-response questionnaire was distributed to the fi rst-and fourth-year students studying at institutions in the United Kingdom. The paper questionnaire sought to quantify respondent's previous BLS training, factual knowledge of the BLS algorithm using five multiple choice questions(MCQs), and valuate their desire for further BLS training. Students received 1 point for each correctly identifi ed answer to the 5 MCQ's.RESULTS: A total of 3,732 complete responses were received from 21 medical schools. Eighty percent(n=2,999) of students completed a BLS course as part of their undergraduate medical studies. There was a signifi cant difference(P<0.001) in the percentage of the fourth-year students selecting the correct answer in all the MCQ's compared to the fi rst-year students except in identifyingthe correct depth of compressions required during CPR(P=0.095). Overall 10.3%(95% CI 9.9% to 10.7%) of respondents correctly identified the answer to 5 MCQ's on BLS: 9% of the first-year students(n=194) and 12% of the fourth-year students(n=190). On an institutional level the proportion of students answering all MCQ's correctly ranged from 2% to 54% at different universities. Eighty-one percent of students(n=3,031) wished for more BLS training in their curriculum.CONCLUSION: Factual knowledge of BLS is poor among medical students in the UK. There is a disparity in standards of knowledge across institutions and respondents indicating that they would like more training.
文摘AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis(NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH.METHODS: This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome(Met S) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients receivedlifestyle advice and were treated for a 12 mo period with rosuvastatin(10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid(SUA), high sensitivity C reactive protein(hs CRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values.RESULTS: The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20 th, which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3rd treatment month(ANOVA P < 0.001), while alkaline phosphatase activities by the 6th treatment month(ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced(P < 0.001). Lipid values were normalised by the 3rd treatment month. No patient had Met S by the 9th treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group.CONCLUSION: These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve Met S within 12 mo. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies.
基金Supported by the European Union on EC contract QLK2-CT-2001-01216(ADRI)
文摘AIM: To investigate the bactericidal and anti-adhesive properties of 25 plants against Helicobacter pylori (H pylori).METHODS: Twenty-five plants were boiled in water to produce aqueous extracts that simulate the effect of cooking. The bactericidal activity of the extracts was assessed by a standard kill-curve with seven strains of H pylori. The anti-adhesive property was assessed by the inhibition of binding of four strains of FITC-labeled H pylori to stomach sections. RESULTS: Of all the plants tested, eight plants, including Bengal quince, nightshade, garlic, dill, black pepper, coriander, fenugreek and black tea, were found to have no bactericidal effect on any of the isolates. Columbo weed, long pepper, parsley, tarragon, nutmeg, yellow-berried nightshade, threadstem carpetweed, sage and cinnamon had bactericidal activities against H pylori, but total inhibition of growth was not achieved in this study. Among the plants that killed H pylori, turmeric was the most efficient, followed by cumin, ginger, chilli, borage, black caraway, oregano and liquorice. Moreover, extracts of turmeric; borage and parsley were able to inhibit the adhesion of H pylori strains to the stomach sections.CONCLUSION: Several plants that were tested in our study had bactericidal and/or anti-adhesive effects on H pylori. Ingestion of the plants with anti-adhesive properties could therefore provide a potent alternative therapy for H pylori infection, which overcomes the problem of resistance associated with current antibiotic treatment.
文摘During liver resection surgery for cancer or liver transplantation,the liver is subject to ischaemia (reduction in blood flow) followed by reperfusion (restoration of blood flow),which results in liver injury [ischemiareperfusion (IR) or IR injury]. Modulation of IR injury can be achieved in various ways. These include hypothermia,ischaemic preconditioning (IPC) (brief cycles of ischaemia followed by reperfusion of the organ before the prolonged period of ischaemia i.e. a conditioning response),ischaemic postconditioning (conditioning after the prolonged period of ischaemia but before the reperfusion),pharmacological agents to decrease IR injury,genetic modulation of IR injury,and machine perfusion (pulsatile perfusion). Hypothermia decreases the metabolic functions and the oxygen consumption of organs. Static cold storage in University of Wisconsin solution reduces IR injury and has prolonged organ storage and improved the function of transplanted grafts. There is currently no evidence for any clinical advantage in the use of alternate solutions for static cold storage. Although experimental data from animal models suggest that IPC,ischaemic postconditioning,various pharma-cological agents,gene therapy,and machine perfusion decrease IR injury,none of these interventions can be recommended in clinical practice. This is because of the lack of randomized controlled trials assessing the safety and efficacy of ischaemic postconditioning,gene therapy,and machine perfusion. Randomized controlled trials and systematic reviews of randomized controlled trials assessing the safety and efficacy of IPC and various pharmacological agents have demonstrated biochemical or histological improvements but this has not translated to clinical benefit. Further well designed randomized controlled trials are necessary to assess the various new protective strategies in liver resection.
文摘The importance of nitric oxide(NO) in vascular physiology is irrefutable;it stimulates the intracellular production of cyclic guanosine monophosphate(cGMP),initiating vascular smooth muscle relaxation.This biochemical process increases the diameter of small arteries,regulating blood flow distribution between arterioles and the microvasculature.The kidney is no exception,since NO predominantly dilates the glomerular afferent arterioles.It is now evident that the vascular production of cGMP can be augmented by inhibitors of phosphodiesterase type 5(PDE 5),the enzyme which breakdowns this cyclic nucleotide.This has clinical relevance,since diabetic nephropathy(DN) a major microvascular complication of diabetes mellitus and the most common cause of end-stage renal disease,increases intraglomerular capillary pressure,leading to glomerular hypertension.PDE 5 inhibitors may have,therefore,the potential to reduce glomerular hypertension.This review describes the use of PDE 5 inhibitors to improve the metabolic,haemodynamic and inflammatory pathways/responses,all of which are dysfunctional in DN.
文摘Context: Stable angina pectoris in women has often been considered a “soft”d iagnosis, with less-severe prognostic implications than in men, but large-scal e population studies are lacking. Objective: To determine sex differences in the incidence and prognosis of stable angina in a large ambulatory population. Desi gn: Prospective cohort study using linked national registers. Setting: All munic ipal primary health care centers, hospital outpatient clinics, occupational heal th care services, and the private sector in Finland. Participants: Among ambulat ory patients aged 45 to 89 years who had no history of coronary disease, we defi ned new cases of “nitrate angina”based on nitrate prescription(56 441 women an d 34 885 men) or “test-positive angina”based on abnormal invasive or noninvas ive test results(11 391 women and 15 806 men). Potentially eligible patients wer e evaluated between January 1, 1996, and December 31, 1998. Follow-up ended in December 2001. Main Outcome Measures: Coronary mortality at 4 years(n=7906 death s) and fatal and nonfatal myocardial infarction at 1 year(n=3129 events). Results: The age-standardized annual incidence per 100 population of all cases of ang ina was 2.03 in men and 1.89 in women, with a sex ratio of 1.07(95%confidence i nterval[CI], 1.06-1.09). At every age, nitrate angina in women and men was asso ciated with a similar increase in risk of coronary mortality relative to the gen eral population. Women with test-positive angina who were younger than 75 years had higher coronary-standardized mortality ratios than men; for example, among those aged 55 to 64 years, it was 4.69(95%CI, 3.60-6.11) in women compared wi th 2.40(95%CI, 2.11-2.73) in men(P< .001 for interaction). There was a strong, graded relationship between amount of nitrates used and event rates; women usin g higher doses of nitrates had prognoses comparable with those of men. Among pat ients with diabetes and test-positive angina, age-standardized coronary event rates were 9.9 per 100 person-years in women vs 9.3 in men(P=.69), and the full y adjusted male-female sex ratio was 1.07(95%CI, 0.81-1.41). Conclusions: Wom en have a similarly high incidence of stable angina compared with men. Furthermo re, stable angina in women is associated with increased coronary mortality relat ive to women in the general population and, among easily identifiable clinical s ubgroups, has similarly high absolute rates of prognostic outcomes compared with men.
文摘Significant concerns over the health,social and economic burdens of the two most common,and frequently co-misused drugs of abuse,alcohol and tobacco,has encouraged focused but separate health promotion and disease prevention policies.However,this separation of focus means that while individuals who present with alcohol-related problems are increasingly supported to attain and maintain abstinence from alcohol they are not routinely assisted to refrain from smoking.This is tragically inopportune as alcohol and tobacco have an established"synergistic"effect on aerodigestive cancer risk.Moreover,even when patients successfully tackle their alcohol problems they remain at increased risk for developing these cancers,especially if they continue to smoke.A case series is presented together with a discussion on how service provision for co-misuse could be improved to obviate aerodigestive cancer risk.Given the prevalence of alcohol and tobacco use in the United Kingdom,these observations may have far reaching implications for the individual,health provider(s)and wider society.
基金Supported by National Natural Science Foundation of China (30700373)
文摘Objective To investigate the role of acyl-coenzyme A:cholesterol acyltransferase inhibitor(ACATI) in apoptosis induced by lipids and whether lipids-induced apoptosis is accompanied by increase of free cholesterol in endoplasmic reticulum(ER),in order to further understand the mechanism of lipids-induced apoptosis in advanced atherosclerosis.Methods Human vascular smooth muscle cells(VSMCs) and phorbol 12-myristate 13-acetate(PMA) differentiated THP-1 macrophages were used.Tritiated thymidine incorporation was applied to detect cell proliferation.Cytotoxicity was assessed by lactate dehydrogenase(LDH) release.4',6-diamidino-2-phenylindole(DAPI) staining,caspase-3,-7 assay,and Annexin-V/propidium iodide(PI) staining were used to detect apoptosis.High performance liquid chromatography was used in intracellular free cholesterol and cholesterol ester assay.ER free cholesterol was quantified.Results Different lipids had different effects on proliferation and cytotoxicity of VSMCs.25-hydroxycholesterol(25OHC) had biphasic effects on the proliferation of VSMCs.At low concentration,it stimulated cell proliferation,but turned to proliferation inhibition as concentration reached 15 μg/mL.25OHC and acetylated low density lipoprotein(AcLDL) could respectively induce apoptosis in human VSMCs and PMA differentiated THP-1 macrophages,which was aggravated by ACATI,accompanied by increase of intracellular free cholesterol content.There was also an increase of cholesterol content in ER with AcLDL-induced apoptosis in THP-1 macrophages.Conclusions Lipids could induce apoptosis,accompanied by increase of intracellular free cholesterol content,which could be augmented by ACATI,suggesting that insults resulting in ER free cholesterol rise might be the initiator of apoptosis.
文摘Letters to the editor can provide useful scientific information and evaluation of published work as well as acting as an additional level of peer review.Furthermore,letters are good reading material,especially if they involve a debate between authors.Finally,letters are relatively short.Therefore,inexperienced career researchers can use such an opportunity to practice putting together a cogent argument.However,it is far from an ideal situation if letters are the only(or main)type of article on which to base an academic career.
文摘Objectives: Antiretroviral therapy (ART) has been associated with lipodystrophy in children. We evaluated changes in various anthropometric measurements for the assessment of lipodystrophy and assessed whether there was an association with use of protease inhibitors (PI), non-PI containing ART and/or stavudine (d4T). Methods: Eighty-five HIV-infected children attending the HIV clinic at Great Ormond Street Hospital (GOSH) were included. The average follow-up was 8.4 months (range 3 - 12 months). Body fat redistribution was assessed by anthropometric measurements including skinfold thickness and circumferences of upper and lower limbs. Measurements were converted to age- and sex-adjusted z-scores through development stages including puberty. Results: Sixty children had taken ART;37 received PI-containing;38 received d4T;25 had never been treated. In the studied population, clinically important changes with decreases in biceps (BSF), subscapular skinfolds and total body fat (4SFT) over period of 12 months were observed. Some increase was noticed in triceps skinfolds (TSF). Limbs circumferences remained at the same level. Further we looked at 4 months basis changes in anthropometric measurements stratified by baseline ART. Generally z-scores of anthropometric measurements were lower in therapy naive children when compared to ART groups. PI-based ART regimens resulted in significant increases in BSF with a trend towards increases in TSF, suprailiac and 4SFT. Mid-arm and thigh circumferences were higher in PI compared to naive group. Similarly, significant changes in BSF z-scores were associated with d4T use. Increases were seen in TSF and mid-arm circumference and decreases were observed in subscapular skinfolds and calf circumference z-scores. Conclusions: Body fat redistribution in HIV-infected children with sub-clinical lipodystrophy could be detected by anthropometric measurements, particularly when PI or d4T is included in ART. Over time, changes with increase in arm and trunk fat, and no change or decrease in leg fat were more pronounced among ART-receiving children.
文摘Introduction In my presentation to the 4th International Symposium on Hepatic Failure and Artificial Liver Support in Chongqing on which this paper is based, I was specifically asked to address the question of whether albumin dialysis, as in the Molecular Adsorbents Recirculating System (MARS) did correct known abnormalities of the disturbed pathophysiology in liver failure. Before doing this
文摘目的明确广西隆安县队列HBsAg无症状携带者感染的乙型肝炎病毒(hepatitis B virus,HBV)准种序列长期演化特征。方法收集9名广西隆安县队列HBsAg无症状携带者2004年、2007年、2013年、2019年或2020年4个不同时间点血清样本。酶联免疫吸附测定法检测HBV血清学标志物;聚合酶链式反应(polymerase chain reaction,PCR)荧光探针法检测HBV病毒载量;试剂盒提取HBV DNA;PCR法扩增HBV全基因组,进行二代测序;利用Mega等软件对所获得的序列进行生物信息学分析。结果共获得23份血清样本,309条全长基因准种序列,每份标本平均获得(0.18±0.07)G测序数据量。55.55%(5/9)的研究对象携带的HBV毒株基因型在长期进化过程中发生了基因型转换,PreS/S区系统进化树基因分型结果与全基因组分析结果完全一致;发现B/C、I/C重组体;各研究标本的Sn值范围为0~0.37,D值范围为0~0.11;共检出21种特殊单核苷酸/氨基酸突变位点(S区7种,X区2种,PreC区3种,BCP区9种)和6种缺失突变,发现多联突变组合形式,未发现任何耐药突变,77.8%(7/9)研究对象在2004年携带的HBV毒株发生了BCP区nt1762(A→T)/1764(G→A)双突变和PreC区1896位(G→A)点突变,HBV基因可在无抗病毒药物压力下由突变型可恢复为野生型和(或)野生型转变为突变型;HBV基因组进化率为2.03×10^(-5)~3.50×10^(-3)。结论在HBV自然感染进程中,HBV基因型和重组体、准种复杂性和多样性可随时间发生改变;HBV基因突变型和野生型可相互转换,一定程度上降低了利用基因型和相关突变来预测临床结局的价值;隆安县乙型肝炎表面抗原(hepatitis B surface antigen,HBsAg)无症状携带者HBV基因组进化率很高。
基金This study was supported by the grants from the National Natural Science Foundation of China (No. 30700373) Peking Union Medical College Hospital Foundation (2009), the National Natural Science Foundation of China (No. 81170665) and the Ministry of Health Sector Fund (No. 200802007).
文摘Background Podocyte apoptosis is recently indicated as an early phenomenon of diabetic nephropathy. Pancreatic β-cells exposed to saturated free fatty acid palmitate undergo irreversible endoplasmic reticulum (ER) stress and consequent apoptosis, contributing to the onset of diabetes. We hypothesized that palmitate could induce podocyte apoptosis via ER stress, which initiates or aggravates proteinuria in diabetic nephropathy. Methods Podocyte apoptosis was detected by 4',6-diamidio-2-phenylindole (DAPI) stained apoptotic cell count and Annexin V-PI stain. The expressions of ER molecule chaperone glucose-regulated protein 78 (GRP78), indicators of ER-associated apoptosis C/EBP homologous protein (CHOP), and Bcl-2 were assayed by Western blotting and real-time PCR. GRP78 and synaptopodin were co-localized by immunofluorescence stain. Results Palmitate significantly increased the percentage of cultured apoptotic murine podocytes time-dependently when loading 0.75 mmol/L (10 hours, 13 hours, and 15 hours compared with 0 hour, P 〈0.001) and dose-dependently when loading palmitate ranging from 0.25 to 1.00 mmol/L for 15 hours (compared to control, P 〈0.001). Palmitate time-dependently and dose-dependently increased the protein expression of GRP78 and CHOP, and decreased that of Bcl-2. Palmitate loading ranging from 0.5 to 1.0 mmol/L for 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to control (P 〈0.001), with the maximum concentration being 0.75 mmol/L. Palmitate 0.5 mmol/L loading for 3 hours, 8 hours, and 12 hours significantly increased mRNA of GRP78 and CHOP, and decreased that of Bcl-2 compared to 0 hour (P 〈0.001), with the maximum effect at 3 hours. Confocal microscopy demonstrated that GRP78 expression was significantly increased when exposed to 0.5 mmol/L of palmitate for 8 hours compared to control. Conclusion Palmitate could induce podocyte apoptosis via ER stress, suggesting podocyte apoptosis and consequent proteinuria caused by lipotoxic free fatty acid could be ameliorated by relief of ER stress.
基金Project supported by the Zhejiang Province Science Foundation for Distinguished Young Scholars(No.LR16H040001)the National Natural Science Foundation of China(No.81401167)+1 种基金Medical and Health General Project of Zhejiang Province,China(No.2015KYA122)the Zhejiang Traditional Chinese Medicine Foundation(Nos.2017ZQ020 and 2017ZA091),China
基金Project supported by the China Scholarship Council(No.2013083 30139)the Zhejiang Traditional Chinese Medicine Foundation(No.2015ZQ025)the Ministry of Health Special Fund of China(No.201302013)