常染色体隐性遗传性多囊肾合并先天性肝纤维化一家系3例报告及文献复习

<正>常染色体隐性遗传性多囊肾(autosomal recessive polycystic kidney disease,ARPKD)是一种多发于儿童肾脏和胆道系统的严重单基因遗传病[1],以肝门静脉系统发育不全为特征,包括胆管板重塑缺陷、胆管增生和先天性肝纤维化(congenital hepatic fibrosis,CHF)[2-4]。ARPKD发病率为1∶20 000～40 000,属罕见病[5],合并CHF的发病率更低。本文将一家系(3姐弟)     

Efficacy, safety, and selection of molecular markers of drug resistance by two ACTs in Mali

We conducted a randomized single-blinded trial comparing the efficacy and safety of artesunate (AS) + amodiaquine (AQ, 3 days) versus AS (3 days) + sulfadoxine-pyrimethamine (SP, single dose) versus AS monotherapy (5 days) in Southern Mali. Uncomplicated malaria cases were followed for 28 days. Molecular markers of drug resistance were determined. After identification of recrudescences by genotyping, both artemisinin-based combination therapies (ACTs) reached nearly 100% efficacy at Day 14 and Day 28 versus 98.3% and 96.5% for AS, respectively (P > 0.05). AS + SP significantly selected DHFR and DHPS mutations associated with sulfadoxine and pyrimethamine resistance (P < 0.001), and AS + AQ equally selected PfCRT and PfMDR1 point mutations associated with chloroquine and AQ resistance (P < 0.001). No significant adverse event attributable to any of the study drugs was found. The ACTs were efficacious and safe, but the selection of markers for resistance to the partner drugs raises concerns over their lifespan in areas of intense malaria transmission.     

瞬时弹性成像对不同年龄慢性乙型肝炎肝纤维化患儿的诊断价值

目的评估瞬时弹性成像FibroScan对0～18岁不同年龄段儿童慢性乙型肝炎(CHB)肝纤维化的诊断价值。方法选取解放军总医院第五医学中心2015年6月-2019年12月住院拟行抗病毒治疗的18岁以下的CHB患儿280例,其中学龄前儿童(≤6岁) 157例、学龄儿童(6～12岁) 74例、青少年(12～18岁) 49例。3组均行肝穿刺病理检查评估肝纤维化程度,按Matevia评分分为轻度(0≤F 2)、中度(2≤F 3)、重度(F≥3),同时应用FibroScan进行肝脏硬度值(LSM)测量。比较同一肝纤维化程度下3个年龄段儿童LSM的差异,评估年龄对LSM判定肝纤维化程度的影响。采用受试者工作特征曲线(ROC曲线)分析LSM诊断不同年龄段儿童乙型肝炎显著肝纤维化(F≥2)、进展期肝纤维化(F≥3)的界值。符合正态分布的计量资料多组间比较采用单因素方差分析;不符合正态分布的计量资料多组间比较采用Kruskal-Wallis H检验,进一步两两比较采用Wilcoxon检验。计数资料多组间比较采用χ~2检验。相关性采用Spearman等级相关分析。结果轻度肝纤维化患儿186例,学龄前、学龄、青少年3组轻度肝纤维化患儿LSM分别为4. 9(4. 3～5. 6) kPa、5. 5(4. 5～6. 3) kPa、6. 0(5. 4～7. 0) kPa,其中学龄前组与青少年组比较差异有统计学意义(Z=10. 929,P=0. 003);中度肝纤维化患儿60例,3组中度肝纤维化患儿LSM分别为5. 6(4. 5～6. 5) k Pa、6. 4(5. 4～7. 7) kPa、7. 1(6. 3～8. 0) kPa,其中学龄前组与青少年组比较差异有统计学意义(Z=8. 517,P=0. 011);重度肝纤维化34例,3组重度肝纤维化患儿LSM分别为8. 3(7. 1～9. 2) kPa、9. 1(8. 5～13. 1) k Pa、11. 1(8. 5～12. 0) kPa,3组比较差异无统计学意义(χ~2=4. 553,P=0. 103)。≤12岁患儿LSM与肝纤维化程度显著相关(r=0. 447,P 0. 001)。诊断显著肝纤维化、进展期肝纤维化的界值分别为5. 8 k P、7. 0 kPa,ROC曲线下面积(AUC)分别为0. 74(0. 68～0. 80)、0. 94(0. 90～0. 97); 12岁患儿LSM与肝纤维化程度显著相关(r=0. 722,P 0. 001),诊断显著肝纤维化、进展期肝纤维化的界值分别为6. 6 kP、8. 0 kPa,AUC分别为0. 82(0. 69～0. 92)、0. 95(0. 85～0. 99)。结论 CHB患儿FibroScan检测值LSM与肝纤维化呈显著正相关,可以作为进展期肝纤维化的无创诊断指标。LSM随年龄增长而升高, 12岁患儿的诊断阈值高于≤12岁患儿。     

Blood pressure measurements by the Keito machine. Evaluation versus office blood pressure by physicians

BACKGROUND: The Keito machine offers automatic measurements of blood pressure (BP), height and weight on insertion of coins and has been introduced in pharmacies. DESIGN: Cross-sectional study comparing automatic BP measurements by the Keito machine to office BP measurements by physicians. METHODS: Patients scheduled for pre-catheterisation screening participated in the study. Their BP was first measured using the Keito machine, then by physicians. Office BP was recorded as the last of three consecutive BP measurements recorded with one-min intervals after a five-min rest in the sitting position. In a sub-study BP was measured simultaneously during the Keito measurement by a physician. RESULTS: In 390 consecutive patients average BP was significantly lower with the Keito machine compared to office BP measurements made by the physicians (136/75+/-19/8 mmHg versus 141/79+/-21/10 mmHg, both p<0.001). The correlation coefficient (r) was 0.56 (p<0.001) for systolic BP (SBP) and 0.53 (p<0.001) for diastolic BP (DBP). Bland-Altman analysis showed a mean difference (+/-2 SD) for SBP and DBP of -5 (+/-37) and -4 (+/-17) mmHg, respectively. When defining hypertension (HT) as office SBP> or =140 and/or DBP> or =90 mmHg, the Keito method diagnosed 83% of the systolic and 62% of the diastolic hypertensive population correctly. The classification of systolic and diastolic normotensive was correct in 61% and 86%, respectively. CONCLUSION: Agreement between office and Keito BP is poor. The Keito machine underestimates SBP on average by 5 mmHg and DBP by 4 mmHg, which may be of significance for diagnosing HT and starting anti-hypertensive therapy. However, the difference can be much larger in individual patients. Therefore, the Keito machine cannot be recommended for medical screening of HT or as a replacement for follow-up by physicians.     

Season, fever prevalence and pyrogenic threshold for malaria disease definition in an endemic area of Mali

BACKGROUND: Modelling malaria parasitaemia as function of fever has been proposed as best alternative to estimate the attributable fraction of malaria fever and the sensitivity and specificity of different case definitions of malaria disease. OBJECTIVES: To determine the prevalence of fever and its relation to malaria parasitaemia and to establish a pyrogenic threshold for malaria disease in the area. METHODS: We conducted two cross-sectional surveys in children of 6 months to 9 years of age (2434 during the rainy season of 1993 and 2353 during the dry season of 1994) randomly selected from 21 areas of Bandiagara district, Mali. RESULTS: The relationship between fever and Plasmodium falciparum parasitaemia depends strongly on the season, thus affecting the malaria-attributable fraction of fever cases and the sensitivity and specificity of malaria case definitions. The overall proportion of fever attributable to malaria parasitaemia was 33.6% during the rainy season and 23.3% during the dry season, with the highest proportion occurring among the youngest children. The cut-off value, where the sensitivity curve crosses the specificity curve, was around 3200 pf/microl for all age categories during the rainy season and 200 pf/microl during the dry season. CONCLUSIONS: Malaria remains a main cause of fever in this area of Mali. The pyrogenic threshold of parasitaemia depends strongly on the season, and different cut-off levels of parasitaemia should be used during the two seasons to define malaria cases in this area.     

International collaboration of the E.I. Martsinovsky Institute of Medical Parasitology and Tropical Medicine: assistance for public health in the Republic of Guinea

Within the framework of international collaboration, the E.I. Martsinovsky Institute of Medical Parasitology and Tropical Medicine (IMPTM), I.M. Sechenov First Moscow State Medical University, assisted the Public Health System of the Republic of Guinea in detecting, diagnosing, studying, and preventing tropical infections of viral, bacterial, and parasitic etiologies, and in training national scientific manpower. The work was under way in the Soviet-Guinea Research Microbiology and Virology Laboratory, USSR Ministry of Health, in the Republic of Guinea (now the Pasteur Institute in Guinea (PIG)) in 1978-1991. The circulation of pathogens of a number of tropical infections, the fauna of vectors and carriers of transmissible infections, and their involvement of the circulation of pathogens of these diseases were found in this period. Consultative-and-methodological and medical assistance was given; national higher- and middle-level brainpower trained. It is expedient to restore scientific ties between the IMPTM and the PIG.     

Effect of AndoSan(™) on expression of adhesion molecules and production of reactive oxygen species in human monocytes and granulocytes in vivo

Abstract Background. Oral intake (60 ml daily) over 12 days in eight healthy volunteers of an immunostimulatory extract based on the medicinal mushroom Agaricus blazei Murill (AbM (AndoSan(?))), reduced the monocyte and granulocyte release of mainly proinflammatory cytokines in vivo, suggesting an anti-inflammatory effect. In this foremost in vivo study, the aim was to examine the effect of such AndoSan(?) consumption on the expression of adhesion molecules CD11b, CD11c and CD62L and production of reactive oxygen species (ROS) in leukocytes. Methodology/Principal findings. As shown by flow cytometry, there was a significant increase of CD62L expression on monocytes and granulocytes from before (day 0) compared with 12 days after daily AndoSan(?) consumption. However, only minor alterations and no clear trend in the expression of CD11b and CD11c were detected. Intracellular ROS (mainly superoxide ion) were significantly reduced in these cells from days 0 to 12. Conclusions/Significance. These results support that oral intake of AndoSan(?) exhibits an anti-inflammatory effect in humans in vivo.     

Repeated artemisinin-based combination therapies in a malaria hyperendemic area of Mali: efficacy, safety, and public health impact

Artemisinin-based combination therapies (ACTs) are the first-line treatment of uncomplicated malaria. The public health benefit and safety of repeated administration of a given ACT are poorly studied. We conducted a randomized trial comparing artemether-lumefantrine, artesunate plus amodiaquine (AS+AQ) and artesunate plus sulfadoxine-pyrimethamine (AS+SP) in patients 6 months of age and older with uncomplicated malaria in Mali from July 2005 to July 2007. The patient received the same initial treatment of each subsequent uncomplicated malaria episode except for treatment failures where quinine was used. Overall, 780 patients were included. Patients in the AS+AQ and AS+SP arms had significantly less risk of having malaria episodes; risk ratio (RR) = 0.84 (P = 0.002) and RR = 0.80 (P = 0.001), respectively. The treatment efficacy was similar and above 95% in all arms. Although all drugs were highly efficacious and well tolerated, AS+AQ and AS+SP were associated with less episodes of malaria.     

前列腺肿瘤干细胞是真实存在的

前列腺(包括正常组织和肿瘤)干细胞虽然无法像胚胎干细胞或间充质干细胞那样分化为其他类型的细胞,但其可分化为前列腺管腔上皮细胞,并具有向神经内分泌细胞分化的潜能[J]. 正如Isaccs研究组提到的,前列腺干细胞是非常独特的,因为仅由雄激素受体这一种蛋白就能够决定从干细胞到祖细胞再到中间细胞,最终到管腔上皮细胞的整个分化过程.     

结核感染对慢性阻塞性肺疾病患者肺部感染及营养指标的影响评价

目的回顾分析慢性阻塞性肺疾病急性加重期并或不并肺部结核感染在感染及营养方面指标的差异性,明确结核感染对AECOPD的影响。方法选取2013年7月—2015年6月因急性发作入住我院的COPD患者105例,根据GOLD 2011对COPD的诊断标准及卫生部2008年制定的肺结核诊断标准将其分为无结核组、稳定期组、好转期组及进展期四组。分别在入院时测定患者白细胞计数、中性粒细胞比率、总淋巴细胞计数、淋巴细胞比值、红细胞沉降率、血红蛋白浓度、血清白蛋白及C反应蛋白及体重指数。结果各组感染指标比较,WBC、CRP两指标差异不显著(P>0.05),而无结核组相较于其他三组,NEUT%更高(F=4.004,P=0.010)、LY%及ESR更低(F/P分别为3.668/0.015和20.197/0.000);各组营养指标比较,合并有肺结核的三组,其Hb、ALB及BMI均比无结核组低,达到统计学差异(P<0.05),而TLC在各组间无差异(F=0.858,P=0.466)。结论合并有结核感染的AECOPD患者更容易出血贫血(Hb降低)、低蛋白血症(ALB降低)、低体重(BMI降低)、中性粒细胞含量偏低(NEUT%降低)而血沉(ESR)、淋巴细胞比率(LY%)升高的情况,对出现此类情况的AECOPD患者应进行结核感染相关检查。