Learning from nature – Novel synthetic biology approaches for biomaterial design

Many biomaterials constructed today are complex chemical structures that incorporate biologically active components derived from nature, but the field can still be said to be in its infancy. The need for materials that bring sophisticated properties of structure, dynamics and function to medical and non-medical applications will only grow. Increasing appreciation of the functionality of biological systems has caused biomaterials researchers to consider nature for design inspiration, and many examples exist of the use of biomolecular motifs. Yet evolution, nature’s only engine for the creation of new designs, has been largely ignored by the biomaterials community. Molecular evolution is an emerging tool that enables one to apply nature’s engineering principles to non-natural situations using variation and selection. The purpose of this review is to highlight the most recent advances in the use of molecular evolution in synthetic biology applications for biomaterial engineering, and to discuss some of the areas in which this approach may be successfully applied in the future.     

热毒宁注射液治疗50例小儿病毒性肠炎的临床疗效观察

目的探讨热毒宁注射液治疗小儿病毒性肠炎的临床疗效与安全性。方法将100例患儿随机分为观察组和对照组各50例,对照组静脉点滴病毒唑,观察组静脉点滴热毒宁注射液,均治疗3 d;比较2组治疗后的临床疗效、止泻时间、退热时间、治愈时间的差异。结果观察组总有效率、止泻时间、退热时间、治愈时间均明显优于对照组,差异有统计学意义(P<0.01)。结论热毒宁治疗病毒性肠炎患儿能有效改善发热、腹泻的症状,提高治疗效果,缩短治疗疗程,值得临床推广使用。     

Expression of hepatitis B surface antigen subtypes in liver of patients with hepatocellular carcinoma; comparison of subtypes in serum and liver

ABSTRACT— To clarify the discrepancy in hepatitis B surface antigen (HBsAg) subtypes present in the serum and liver, as well as among hepatocytes, liver specimens which were resected from 37 HBsAg-positive patients with hepatocellular carcinoma (HCC) were examined. We evaluated HBsAg and the subtypic determinants of HBsAg and hepatitis B core antigen (HBcAg) using the peroxidase-antiperoxidase (PAP) staining method. Hepatitis B antigens were more frequently detected in small tumors (HBsAg in 67%, HBcAg in 40%) than in large ones (HBsAg in 36%, HBcAg in 14%). The prevalence of each subtypic determinant in the HBsAg positive non-tumorous vs. tumorous areas was 100% vs. 67% in a, 100% vs. 57% in d, 100% vs. not tested in y, 100% vs. 53% in r and 25% vs. 0% in w (a, d, y, r and w represent subtypic determinants). There was virtually no difference in a set of subtypic determinants between the serum and liver. However, there were some variations in a set of subtypic determinants among the hepatocytes. On the other hand, liver tissue of compound subtype adyr in serum contained both cells with a,d,r and with a,y,r as well as a few cells with a,d,y,r. These findings suggest that HBV genomes in hepatocytes of type B chronic liver disease may differ genetically among cells even in the same liver tissue.     

Sustained Viral Response Is Rarely Achieved in Patients with High Viral Load of HCV RNA by Excessive Interferon Therapy

Adequate dosing of interferon (IFN) and its cost-effectiveness for sustained virological response were evaluated in relation to viral load and subtype. Prospective analysis of IFN therapy on 326 patients with chronic hepatitis C free from cirrhosis was performed using 9 or 6 million unit (MU) of IFN for six months daily and/or three times a week. Sustained virological response was achieved in 50–94% of patients with 2 × 10⁴ copies/ml (competitive RT-PCR) or <100 × 10³ copies/ml (Amplicor monitor) of HCV RNA by 468–1206 MU of IFN, but response was only 0–25% of the patients with 2 × 10^5.5 copies/ml (competitive RT-PCR) or >200 × 10³ copies/ml (Amplicor monitor), even with 468–1206 MU of IFN. A high sustained rate was demonstrated in patients with 100–200 × 10³ copies/ml of HCV RNA by 901–1206 MU of IFN, in comparison to that with 900 MU of IFN. Multivariate analysis showed that IFN dose had a significant value for the efficacy of IFN therapy in patients presenting 100–200 × 10³ copies/ml of HCV RNA. Cost efficacy analysis indicated that it cost approximately $10,000, $26,000, and $50,000–227,000 for one person-viral eradication in the patients with <100, 100–200, and >200 × 10³ copies/ml, respectively. High-dose IFN is only cost effective in patients with intermediate viral loads, and IFN therapy could be recommended in patients with <200 × 10³ copies/ml of HCV RNA.     

利用甲型流感病毒阳性标本制备质控品的研究

目的 制备一种能适用于甲型流感病毒核酸提取、PCR检测的全程质控品。方法 采用TRIzol试剂灭活高中低三种浓度的甲型流感病毒阳性的临床标本,分析TRIzol试剂对检测结果的影响;放置于不同温度以及反复冻融,评估灭活后标本的稳定性。结果 TRIzol试剂对核酸检测无明显影响,处理后的高、中、低浓度标本反复冻融40次病毒浓度无明显降低,变异系数分别为1.26%、1.54%、1.54%,均低于试剂盒批间精密度。TRIzol试剂处理的标本在35℃环境保存40天开始有下降趋势,高中低浓度变异系数分别为3.13%、2.77%、2.20%,变异系数均低于试剂盒批间精密度。TRIzol试剂处理的标本在25℃环境、保存40天的过程中病毒浓度无明显降低,变异系数均低于试剂盒批内精密度。结论 临床实验室可采用TRIzol试剂灭活甲型流感病毒阳性标本制备质控品。     

地氯雷他定联合复方甘草酸苷治疗慢性荨麻疹的临床观察

目的观察地氯雷他定联合复方甘草酸苷对慢性荨麻疹患者的临床疗效。方法将笔者医院从2013年1~6月收治的140例慢性荨麻疹患者按随机数表法均分为实验组70例和对照组70例,实验组采用地氯雷他定联合复方甘草酸苷治疗,对照组单用地氯雷他定治疗。比较两组CD4+和CD8+淋巴细胞比例的变化、临床疗效、治疗后复发率以及药物不良反应的发生率。结果治疗前两组CD4+和CD8+淋巴细胞亚群比例差异无统计学意义(P>0.05);治疗后,CD8+淋巴细胞两组均出现显著减低(P<0.05),CD4+淋巴细胞和CD4+/CD8+比值两组均出现显著升高(P<0.05),但治疗后实验组CD4+淋巴细胞和CD4+/CD8+比值均显著高于对照组(P<0.05),而CD8+淋巴细胞实验组又显著低于对照组(P<0.05)。实验组临床治疗有效率为87.1%显著高于对照组的75.8%(P<0.05)。随访6个月后实验组和对照组复发率分别为55.7%和72.9%,两组之间差异具有统计学意义(P<0.05)。实验组不良反应发生率为8.6%,对照组不良反应发生率为7.1%,两组之间差异无统计学意义(P>0.05)。结论地氯雷他定联合复方甘草酸苷能有效治疗慢性荨麻疹,安全有效,且能减少复发。     

慢性乙肝患者的免疫状态与病毒载量及抗病毒疗效的关系研究

目的 探讨慢性乙肝(chronic hepatitis B,CHB)患者的机体免疫状态与病毒载量及抗病毒疗效的关系.方法 将237例CHB患者按照乙肝病毒(hepatitis B virus,HBV)载量,分为病毒阴性组、低病毒载量组和高病毒载量组,比较各组的免疫球蛋白、补体及T细胞亚群等免疫指标的差异.对其中符合抗HBV治疗指征的患者给予抗HBV治疗,观察治疗半年后的病毒学应答情况和治疗1年后的e抗原血清学应答情况,分析初始免疫状态与抗病毒疗效的关系.结果 随着HBV-DNA载量的升高,CHB患者的CD3+、CD4+及CD8+T细胞计数随之升高,而CD4+/CD8+比值随之下降(P＜0.05).完全病毒学应答组和部分/无病毒学应答组的初始免疫指标比较,差异无统计学意义(P＞0.05).获得e抗原血清学转换者与未获得e抗原血清学转换者相比,在开始抗病毒治疗时的ALT和AST水平更高(P＜0.05),但初始免疫指标差异无统计学意义(P＞0.05).结论 CHB患者的免疫状态与HBV-DNA载量相关,CD3+、CD4+及CD8+T细胞计数随着HBV-DNA载量的升高而升高,而CD4+/CD8+比值则随之下降.CHB患者在抗病毒治疗时的初始免疫状态与病毒学应答及e抗原血清学转换无明显相关性.     

Acute bronchiolitis during the COVID-19 pandemic

IntroductionThe autumn and winter bronchiolitis epidemics have virtually disappeared in the first year of the COVID-19 pandemic.Our objectives were characterised bronchiolitis during fourth quarter of 2020 and the role played by SARS-CoV-2.MethodsProspective multi-centre study performed in Madrid (Spain) between October and December 2020 including all children admitted with acute bronchiolitis. Clinical data were collected and multiplex PCR for respiratory viruses were performed.ResultsThirty-three patients were hospitalised with bronchiolitis during the study period: 28 corresponded to rhinovirus (RV), 4 to SARS-CoV-2, and 1 had both types of infection. SAR-CoV-2 bronchiolitis were comparable to RV bronchiolitis except for a shorter hospital stay. A significant decrease in the admission rate for bronchiolitis was found and no RSV was isolated.ConclusionSARS-CoV-2 infection rarely causes acute bronchiolitis and it is not associated with a severe clinical course. During COVID-19 pandemic period there was a marked decrease in bronchiolitis cases.     

Incidence of Hepatitis C Virus Infections Among Users of Human Immunodeficiency Virus Pre-exposure Prophylaxis

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