Development of health biotechnology in developing countries: Can private-sector players be the prime movers?

Health biotechnology has rapidly become vital in helping healthcare systems meet the needs of the poor in developing countries. This key industry also generates revenue and creates employment opportunities in these countries. To successfully develop biotechnology industries in developing nations, it is critical to understand and improve the system of health innovation, as well as the role of each innovative sector and the linkages between the sectors. Countries' science and technology capacities can be strengthened only if there are non-linear linkages and strong interrelations among players throughout the innovation process; these relationships generate and transfer knowledge related to commercialization of the innovative health products. The private sector is one of the main actors in healthcare innovation, contributing significantly to the development of health biotechnology via knowledge, expertise, resources and relationships to translate basic research and development into new commercial products and innovative processes. The role of the private sector has been increasingly recognized and emphasized by governments, agencies and international organizations. Many partnerships between the public and private sector have been established to leverage the potential of the private sector to produce more affordable healthcare products. Several developing countries that have been actively involved in health biotechnology are becoming the main players in this industry. The aim of this paper is to discuss the role of the private sector in health biotechnology development and to study its impact on health and economic growth through case studies in South Korea, India and Brazil. The paper also discussed the approaches by which the private sector can improve the health and economic status of the poor.     

Molecular Biology of Background K Channels: Insights from K2P Knockout Mice

K_2P channels are a family of cellular proteins that are essential for electrical signaling throughout the body. There are six K_2P channel subfamilies, consisting of 15 distinct mammalian genes. K_2P channels display a remarkable range of regulation by cellular, physical and pharmacologic agents, including protein kinases, intracellular Ca²⁺, changes in internal and external pH, anesthetic agents, heat, stretch and membrane deformers. The molecular and cellular mechanisms underlying this regulation are complex and cooperate at many different levels. Recent research has provided strong evidence that the spatiotemporal-specific expression of K_2P channels are determinants of physiologic selectivity and specificity. In recent years, knockout mice have been generated with inactivated K_2P channel genes. These animals shed new light on the contribution of K_2P channels to normal and abnormal physiology. In this review, we summarize the published data on these mice to broaden the understanding of the role of K_2P channel activity.     

Abnormal kinetic behavior of uroporphyrinogen decarboxylase obtained from rats with hexachlorobenzene-induced porphyria

Uroporphyrinogen decarboxylase is an essential enzyme in all organisms and functions in the heme biosynthetic pathway, catalyzing the decarboxylation of the four acetate groups of uroporphyrinogen to form coproporphyrinogen. This work examines whether the four sequential decarboxylations occur at the same active site, and explores whether hexachlorobenzene-induced porphyria affects the behavior of the enzyme. For this purpose, kinetic competition studies were done with mixtures of uroporphyrinogen III and pentacarboxyporphyrinogen III. With the enzyme from normal rats, a constant velocity was obtained with all the mixtures, indicating that uroporphyrinogen and pentacarboxy-porphyrinogen react at the same active site, i.e. the first and fourth decarboxylations occur at the same site. In contrast, in experiments with enzyme from rats with hexachlorobenzene-induced porphyria, the total rate for mixtures was always lower than the reference rate; and a curve with a deep minimum was obtained, indicating that the two reactions occur at functionally different sites, but with cross-inhibition. This suggests that the modifications induced in the enzyme by hexachlorobenzene cause the two active sites to become nonequivalent and functionally different. The question is discussed how the hexachlorobenzene treatment may produce this abnormal kinetic behavior, and alternative hypotheses are considered.     

PCT及CRP在急性肠梗阻大鼠血清中的表达水平及其临床意义

目的:探讨降钙素原(Procalcitonin,PCT)及C反应蛋白(C-reactive protein,CRP)在急性肠梗阻大鼠血清中的水平及其临床意义。方法:将83只Wistar大鼠分为对照组(n=13)、假手术组(n=35)和急性肠梗阻组(n=35)。对照组大鼠采集标本后处死,肠梗阻组行开腹手术结扎回肠末端,假手术组仅行开腹手术。检测8 h、24 h、48 h、72 h及96 h血清PCT及CRP水平,观察急性肠梗阻大鼠回肠组织的病理学改变情况。结果:假手术组PCT与CRP水平在术后24 h内显著升高,48 h至96 h逐渐下降;各时间点PCT水平明显高于对照组,而CRP水平在实验结束时已恢复至正常水平。肠梗阻组PCT和CRP水平在各时间点均明显高于对照组,并逐渐增加,到实验结束时达到高峰;肠梗阻组PCT和CRP水平在48 h-96 h均显著高于假手术组,差异具有统计学意义(P0.05)。组织病理学检查显示,对照组大鼠肠壁粘膜结构正常,假手术组可见轻度病理改变,肠梗阻组大鼠回肠组织可见粘膜结构明显破坏,绒毛坏死,严重水肿和炎症细胞浸润。结论:血浆PCT和CRP水平能够反映肠梗阻的状态和肠粘膜受损程度。     

溃疡性结肠炎患者外周血C 反应性蛋白、血清降钙素原及白细胞介素-6 水平及临床意义

目的:分析溃疡性结肠炎(Ulcerative colitis,UC)患者血清降钙素原(Procalcitonin,PCT)、C反应蛋白(C-reactive protein,CRP)及白细胞介素-6(Interleukin-6,IL-6)水平与病情严重程度的关系。方法:选择2013年5月-2015年5月在我院就诊的溃疡性结肠炎患者91例作为研究对象,另选择同期在我院接受健康体检的志愿者69例作为对照组。检测并比较两组研究对象血清降钙素原(PCT)、C反应性蛋白(CRP)及白细胞介素-6(IL-6)的水平,并分析PCT,CRP及IL-6水平与溃疡性结肠炎的相关性。结果:溃疡性结肠炎患者PCT水平为(1.24±0.23)ng/m L,对照组PCT水平为(0.12±0.10)ng/m L,溃疡性结肠炎患者PCT水平显著高于对照组,差异具有统计学意义(P0.05);溃疡性结肠炎患者CRP水平为(105.27±19.93)mg/m L,对照组CRP水平为(7.62±2.97)mg/m L,溃疡性结肠炎患者血清CRP水平显著高于对照组,差异具有统计学意义(P0.05);溃疡性结肠炎患者IL-6水平为(248.15±35.60)ng/m L,对照组IL-6水平为(144.05±20.26)ng/m L,溃疡性结肠炎患者血清IL-6水平显著高于对照组,差异具有统计学意义(P0.05)。溃疡性结肠炎患者血清PCT,IL-6及CRP水平之间均呈正相关关系(r=0.301,0.468,0.413,P0.01)。结论:溃疡性结肠炎患者血清PCT,CRP及IL-6水平均显著高于健康人群,其水平变化与患者病情严重程度有关。因此,我们在临床实践中应予以重视。     

2型糖尿病并发肺结核患者PCT、HMGB1、CD4+/CD8+比值与继发肺部感染的关系

摘要 目的：探讨2型糖尿病并发肺结核患者降钙素原（PCT）、高迁移率族蛋白1（HMGB1）、CD4⁺/CD8⁺比值与继发肺部感染的关系。方法：选择2019年1月至2022年6月四川大学华西医院呼吸与危重症医学科收治的97例2型糖尿病并发肺结核患者,根据入院治疗时是否继发肺部感染分为肺部感染组（53例）及非肺部感染组（44例）。检测两组血清PCT、HMGB1水平以及外周血CD4⁺/CD8⁺比值。单因素和多因素Logistic回归分析2型糖尿病并发肺结核患者继发肺部感染的因素。受试者工作特征（ROC）曲线分析PCT、HMGB1和CD4⁺/CD8⁺比值预测2型糖尿病并发肺结核患者继发肺部感染的价值。结果：肺部感染组血清PCT、HMGB1水平高于非肺部感染组（P＜0.05）,外周血CD4⁺/CD8⁺比值低于非肺部感染组（P＜0.05）。糖化血红蛋白及血清PCT、HMGB1水平升高是2型糖尿病并发肺结核患者继发肺部感染的危险因素（P＜0.05）,高CD4⁺/CD8⁺比值是保护因素（P＜0.05）。PCT、HMGB1、CD4⁺/CD8⁺比值预测2型糖尿病并发肺结核患者继发肺部感染的曲线下面积为0.719、0.761、0.738,联合PCT、HMGB1和CD4⁺/CD8⁺比值预测的曲线下面积为0.878,高于各指标单独预测。结论：2型糖尿病并发肺结核患者血清PCT、HMGB1水平增高,外周血CD4⁺/CD8⁺比值降低,均与继发肺部感染有关,PCT、HMGB1联合CD4⁺/CD8⁺比值可辅助预测2型糖尿病并发肺结核患者继发肺部感染的风险。     

血清PCT、sICAM-1联合HMGB1预测急性阑尾炎患儿手术切口感染风险的临床研究

摘要 目的：探讨血清降钙素原（PCT）、可溶性细胞间粘附分子-1（sICAM-1）联合高迁移率族蛋白B1（HMGB1）预测急性阑尾炎（AA）患儿手术切口感染风险的价值。方法：前瞻性选取2020年1月～2022年7月四川大学华西医院小儿外科收治的536例接受腹腔镜手术的AA患儿,根据术后是否发生手术切口感染分为感染组和未感染组。采用酶联免疫吸附法检测血清PCT、sICAM-1、HMGB1水平。采用多因素Logistic回归分析AA患儿手术切口感染的影响因素,采用受试者工作特征（ROC）曲线分析血清PCT、sICAM-1、HMGB1水平对AA患儿手术切口感染的预测价值。结果：536例AA患儿腹腔镜手术后手术切口感染发生率为11.94%（64/536）。与未感染组比较,感染组血清PCT、sICAM-1、HMGB1水平升高（P＜0.05）。多因素Logistic回归分析显示,病程＞24 h、阑尾穿孔、手术操作时间＞60 min、留置腹腔引流和PCT、sICAM-1、HMGB1水平升高为AA患儿手术切口感染的独立危险因素（P＜0.05）。ROC曲线分析显示,血清PCT、sICAM-1联合HMGB1预测AA患儿手术切口感染的曲线下面积（AUC）大于PCT、sICAM-1、HMGB1单独预测。结论：血清PCT、sICAM-1、HMGB1水平升高与AA患儿手术切口感染密切相关,血清PCT、sICAM-1联合HMGB1预测AA患儿手术切口感染的价值较高,可能成为AA患儿手术切口感染的辅助预测指标。     

急性阑尾炎患者术后切口感染的病原菌分析及NLR、PCT、CRP联合检测的预测价值研究

摘要 目的：分析急性阑尾炎（AA）患者术后切口感染的病原菌并探讨中性粒细胞与淋巴细胞比值（NLR）、降钙素原（PCT）、C反应蛋白（CRP）联合检测的预测价值。方法：选取2020年1月～2022年9月青岛大学附属医院收治的379例接受腹腔镜或开腹手术的AA患者,根据是否发生术后切口感染分为感染组和非感染组,收集AA患者临床资料并检测NLR、PCT、CRP水平。分析术后切口感染AA患者病原菌分布情况,采用单因素和多因素Logistic回归分析AA患者术后切口感染的影响因素,采用受试者工作特征（ROC）曲线分析NLR、PCT、CRP对AA患者术后切口感染的预测价值。结果：379例AA患者术后切口感染发生率为12.40%（47/379）,47例术后切口感染AA患者切口分泌物共检测出75株病原菌,革兰氏阳性菌和革兰氏阴性菌分别占比42.67%（32/75）、57.33%（43/75）。感染组NLR、PCT、CRP水平高于非感染组（P＜0.05）。多因素Logistic回归分析显示,年龄≥60岁、病程≥24 h、阑尾化脓或坏疽及穿孔、开腹手术、留置引流管和血清NLR、PCT、CRP升高为AA患者术后切口感染的独立危险因素,预防性应用抗菌药物为其独立保护因素（P＜0.05）。ROC曲线分析显示,NLR、PCT、CRP联合预测AA患者术后切口感染的曲线下面积大于NLR、PCT、CRP单独预测。结论：术后切口感染AA患者病原菌以革兰氏阴性菌为主,术前NLR、PCT、CRP水平升高与AA患者术后切口感染密切相关,三者联合预测AA患者术后切口感染的价值较高。     

Temporal changes in breast cancer incidence in South Asian women

BackgroundBreast cancer in the UK resident population of South Asian ethnicity has been lower than that in indigenous women. Leicester has a large South Asian population and a breast cancer unit with comprehensive data on diagnosed cancers. This study analysed the annual incidence of new breast cancer diagnoses in females from 1998 to 2009 to determine any changes in recent years.MethodsEthnicity was known in over 98% of cases. Population denominators were based on published figures for 2001 and 2011, projected back to 1998. Age-adjusted directly standardised incidence rates were determined by ethnicity and broken down by invasive status and screening classification. Incidence rates were analysed using logistic regression in order to identify statistically significant effects of age, ethnicity, deprivation and year of diagnosis. Interactions with invasive status and screening classification were also investigated.ResultsAt the start of the study period South Asian incidence was estimated to be 45% of that of the white population (p < 0.001); by the end of the period the difference was still significant (p = 0.022) but smaller, at 17%.ConclusionSouth Asians should no longer be considered at low risk of breast cancer.     

PCT、IL-6、CRP、NLR在ICU细菌性血流感染患者革兰氏阳性菌和阴性菌中的鉴别作用及对死亡风险的预测价值

摘要 目的：探讨降钙素原（PCT）、白细胞介素-6（IL-6）、C反应蛋白（CRP）、中性粒细胞/淋巴细胞比值（NLR）在重症加强护理病房（ICU）细菌性血流感染（BSI）患者革兰氏阳性菌（G⁺菌）和阴性菌（G^-菌）中的鉴别作用及对死亡风险的预测价值。方法：选取2019年2月～2021年12月我院收治的99例细菌性BSI患者,根据细菌革兰氏染色培养鉴定结果分为G^-菌感染组和G⁺菌感染组,检测并比较两组PCT、IL-6、CRP、NLR水平,并以受试者工作特征（ROC）曲线分析上述指标对G⁺菌和G^-菌感染的鉴别价值。比较G⁺菌、G^-菌不同病原菌类型的PCT、IL-6、CRP、NLR水平差异。此外,将所有患者根据28 d预后差异分为死亡组和存活组,比较两组PCT、IL-6、CRP、NLR水平,以ROC曲线分析上述指标对ICU细菌性BSI患者死亡的预测价值。结果：（1）99例细菌性BSI患者中,病原菌类型为G^-菌的70例（70.71%）,G⁺菌29例（29.29%）。（2）G^-菌感染组PCT、NLR水平均高于G⁺菌感染组（P＜0.05）,而两组IL-6及CRP水平对比差异不明显（P＞0.05）。联合检测PCT、NLR水平鉴别G⁺菌和G^-菌的ROC-AUC（0.95CI）为0.855（0.770～0.912）,鉴别效能较好。（3）肺炎克雷伯菌PCT、IL-6、CRP水平均高于大肠埃希菌、鲍曼不动杆菌、铜绿假单胞菌以及其他G^-菌,NLR水平则低于大肠埃希菌、鲍曼不动杆菌、铜绿假单胞菌以及其他G^-菌（P＜0.05）。链球菌属PCT、IL-6、CRP、NLR水平均高于凝固酶阴性葡萄球菌、金黄色葡萄球菌以及肠球菌属（P＜0.05）。（4）死亡组患者的PCT、IL-6、NLR水平均高于存活组（P＜0.05）,而两组CRP水平对比差异不明显（P＞0.05）。联合检测PCT、IL-6、NLR水平预测ICU细菌性BSI患者死亡的ROC-AUC（0.95CI）为0.871（0.787～0.937）,预测效能较好。结论：联合检测PCT、NLR在鉴别ICU细菌性BSI患者G^-菌和G⁺菌方面具有一定价值,而联合检测PCT、IL-6、NLR对患者死亡风险具有一定预测价值。