沙参麦冬汤加减对阴虚肺热证肺炎支原体肺炎恢复期患者免疫炎症反应的影响

目的:观察沙参麦冬汤加减对肺炎支原体肺炎恢复期患者阴虚肺热证的疗效及对免疫炎症反应的调节作用。方法:将148例患者按随机数字表法分为对照组和观察组各74例。研究期间对照组脱落、失访2例,剔除3例完成70例;观察组脱落、失访4例,完成71例。两组患者均口服阿奇霉素片,10 mg·kg~(-1)·d~(-1),连服3 d;和匹多莫德颗粒剂,0.4～0.8 g/次,2次/d;和氨溴特罗口服溶液,2.5～15 mL/次,2次/d。对照组口服养阴清肺口服液,5～10 mL/次,2～3次/d;观察组内服沙参麦冬汤加减,1剂/d。两组疗程均为7 d。进行治疗前后咳嗽症状评分和咳嗽视觉模拟评分(VAS);记录咳嗽、肺部湿啰音,咯痰消失时间和胸片复常时间;进行治疗前后阴虚肺热证评分和莱塞斯特咳嗽问卷(LCQ)评分;检测治疗前后T淋巴细胞亚群(CD3+,CD4+,CD8+和CD4+/CD8+)和白细胞介素-6(IL-6),IL~(-1)0,肿瘤坏死因子-α(TNF-α),P物质(SP),降钙素原基因相关肽(CGRP)水平;进行治疗后安全性评价。结果:观察组疾病疗效总有效为95.77%(68/71),优于对照组的82.86%(58/70)(χ2=6.186,P0.05);观察组患者咳嗽症状积分和VAS评分均明显低于对照组(P0.01);观察组患者LCQ量表各维度评分和LCQ总分均高于对照组(P0.01);观察组患者咳嗽、肺部湿啰音、咯痰消失时间及胸片复常时间均短于对照组(P0.01);观察组CD3+,CD4+,CD4+/CD8+均高于对照组(P0.01),CD8+低于对照组(P0.01);观察组血清IL-6,IL~(-1)0,TNF-α水平和痰液中SP和CGRP水均低于对照组(P0.01)。结论:在西医常规治疗的基础上,采用沙参麦冬汤加减内服治疗MPP恢复期阴虚肺热证患者,可减轻咳嗽程度,缩短病程,改善了生活质量,提高了细胞免疫功能,减轻了炎性损伤,降低了咳嗽敏感性,有较好的临床疗效,且使用安全。     

Hyaluronan-based delivery of therapeutic oligonucleotides for treatment of human diseases

Introduction: Oligonucleotide therapeutics such as antisense oligonucleotides and siRNA requires chemical modifications and nano-sized carriers to circumvent stability problems in vivo, to reach target tissues, and to overcome tissue and cellular barriers. Hyaluronic acid (HA), already utilized in drug delivery and tissue engineering, possess properties that are useful to solve these problems and achieve full potential of oligonucleotide therapeutics.

Areas covered: Complexes of oligonucleotide therapeutics with HA are discussed in terms of interactions providing the complexes formation and genes targeted by the therapeutics to cure diseases such as cancer, atherosclerosis, liver cirrhosis, and inflammation. The achieved therapeutic effects are rationalized as consequences of biodistribution, cell internalization and endosomal escape provided by HA.

Expert opinion: Design of electrostatic, coordination, and hydrophobic interactions as well as covalent conjugation between oligonucleotide drugs, HA macromolecules and intermediate ligands are crucial for carrier–cargo association and dissociation under different conditions to impart oligonucleotides stability in vivo, their accumulation in diseased organs, cellular uptake, and dissociation in cytoplasm intact. These are the delivery factors that provides eventual complex formation of oligonucleotide therapeutics with their mRNA, microRNA, or protein targets. Elucidation of the impact of structural parameters of oligonucleotide/HA complexes on their therapeutic effect in vivo is important for the future rational design of the delivery agents.     

The influence of polymorphisms in the drug transporter,ABCB1 on the toxicity of glucocorticoids in Saudi children with acute lymphoblastic leukaemia

Background

Glucocorticoids play essential roles in the treatment of childhood acute lymphoblastic leukaemia (ALL); however, treatment with these agents can result in severe side-effects. This study, the first of its kind in a Saudi population, investigates associations of ABCB1 gene polymorphisms (pharmacodynamics and pharmacokinetic) with the development of toxicity and side effects (glucose abnormality, liver toxicity and infection) in a small population of Saudi children with ALL.

低温等离子射频消融术联合顺铂注射液治疗喉癌的疗效观察

目的探讨低温等离子射频消融术联合顺铂注射液治疗喉癌的临床疗效及对患者血管内皮生长因子C(VEGF-C)和PTEN基因的影响。方法选取2017年1月至2018年8月间麻城市人民医院收治的150例喉癌患者,采用随机数表法分为观察组和对照组,每组75例。对照组患者采用喉镜下CO2激光切除术联合顺铂注射液治疗,观察组患者采用低温等离子射频消融术联合顺铂注射液治疗,比较两组患者的治疗效果、血清VEGF-C和PTEN及不良反应。结果观察组患者的临床疗效为72.0%,高于对照组患者的41.3%,差异有统计学意义(P<0.05)。治疗前,两组患者的血清VEGF-C和PTEN比较,差异无统计学意义(P>0.05)。治疗后,两组患者的血清VEGF-C和PTEN均下降,且观察组患者均低于对照组患者,差异均有统计学意义(均P<0.05)。观察组患者总生存时间及无瘤生存时间均高于对照组患者,差异均有统计学意义(均P<0.05)。两组患者的不良反应发生率比较,差异无统计学意义(P>0.05)。结论低温等离子射频消融术联合顺铂注射液治疗喉癌,可降低患者的VEGF-C和PTEN水平,治疗效果较好,建议临床推广。     

Aberrant expression of Wnt/β-catenin signaling pathway genes in aggressive malignant gastric gastrointestinal stromal tumors

IntroductionRecent reports on gene expression profiling (GEP) show several genes associated with malignant progression of GIST. However, genes associated with malignant transformation have not been clarified. Here, we aimed to reveal distinct genes in aggressive malignant GIST, using comprehensive gene expression analysis.Materials and methodsWe investigated GEP obtained by microarrays for 43 gastric GISTs, which mostly harbored KIT and PDGFRA mutations and integrated clinicopathological risk information. RT-PCR and immunohistochemistry were performed for FZD7, a receptor of Wnt ligands.ResultsGEP divided 43 gastric GISTs into two clusters. A cluster included seven of eight high-risk GISTs (88%) in modified NIH classification and was defined as high-risk cluster; the other cluster was defined as low-risk cluster. The number of probes with over 3-fold changes between the two clusters was 1,177, in which probes corresponding to 16 oncogenes were included. Genes involved in the Wnt signaling pathway were the most abundant among the 16 oncogenes. Focusing on 73 Wnt signaling pathway genes of the 21,578 probes, 12 upregulated and 5 downregulated genes were found in the high-risk cluster. Major cascade genes promoting the Wnt/β-catenin signaling pathway, including WNT11, FZD family, and DVL2, were upregulated in the high-risk cluster. SNAI1, SNAI2, and BIRC5, which are activated by this pathway and increase cell proliferation, were also upregulated. These gene expression alterations were consistent in the positive direction of this pathway. GISTs in high-risk cluster strongly expressed FZD7.ConclusionWnt/β-catenin signaling pathway may play an important role in malignant transformation of indolent GIST.     

错配修复基因在右半结肠癌的表达对病理特征的影响

目的:研究散发性结肠癌错配修复基因MLH1、MSH2、MSH6和PMS2在右半结肠癌的蛋白质表达缺失情况,进一步分析错配修复基因的表达缺失与右半结肠癌病理特征的相关性。方法:收集2015年1月至2020年8月期间,在我院就诊的206例结肠癌病人手术切除组织标本及病历资料,左半结肠癌116例,右半结肠癌90例。应用免疫组织化学检测MLH1、MSH2、MSH6和PMS2基因的蛋白质表达情况,分析错配修复基因的蛋白质表达缺失与结肠癌病理特征的相关性。结果:错配修复基因在右半结肠癌的蛋白质表达缺失率高于左半结肠癌。右半结肠癌错配修复基因的蛋白质表达缺失与肿瘤分化程度、肿瘤神经浸润显著相关(P<0.05)。结论:散发性结肠癌中右半结肠癌病人错配修复基因的蛋白质表达缺失比例高于左半结肠癌。错配修复基因的蛋白质表达缺失右半结肠癌病人分化程度低,不易发生神经浸润。     

Adult‐onset inflammatory linear verrucous epidermal nevus: Immunohistochemical studies and review of the literature

Adult‐onset inflammatory linear verrucous epidermal nevus (ILVEN) is an uncommon cutaneous disease compared to childhood‐onset ILVEN. The typical histopathologic features are alternating parakeratosis and orthokeratosis with an absent granular layer underneath parakeratosis, in contrast to a thickened granular layer below the foci of orthokeratosis in psoriasiform epidermal hyperplasia. Herein, we present a 49‐year‐old woman with typical clinical and histopathologic characteristics of adult‐onset ILVEN, including linear arrangement of thick scaly papules and plaques localized on the medial side of her right leg, ankle, and foot. Immunohistochemical studies included involucrin, Ki‐67, and keratin‐10. Compared to the staining pattern in psoriasis, the expression of involucrin in this case was of lower intensity and localized to upper epidermal layers with relatively less extensive staining beneath regions of parakeratosis as compared to orthokeratosis; Ki‐67 showed lower basal layer proliferative activity; and keratin‐10 showed a greater intensity of staining within suprabasal epidermis.