Molecular simplification of lipid A structure: TLR4-modulating cationic and anionic amphiphiles

A growing body of data suggests that therapies based on Toll-like receptors (TLR) targeting, in particular TLR4, holds promise in curing autoimmune and inflammatory pathologies still lacking specific treatment, included several rare diseases. While TLR4 activators (agonists) have already found successful clinical application as vaccine adjuvants, the use of TLR4 blockers (antagonists) as antisepsis agents or as agents against inflammatory diseases (including arthritis, multiple sclerosis, neuroinflammations) and cancer is still at a preclinical phase of development. This minireview focuses on recent achievements on the development of TLR4 modulators based on lipid A structure simplification, in particular on compounds having disaccharide or monosaccharide structures. As the TLR4 activity of natural TLR4 ligands (lipopolysaccharide, LPS and its biologically active part, the lipid A) depends on both the structure of endotoxin aggregates in solution and on single-molecule interaction with MD-2 and CD14 receptors, the rational design of TLR4 modulators should in principle take into account both these factors. In the light of the most recent advances in the field, in this minireview we discuss the structure–activity relationship in simplified lipid A analogs, with cationic or anionic amphiphilic structures.     

Associations of HLA and drug-metabolizing enzyme genes in co-trimoxazole-induced severe cutaneous adverse reactions

Co-trimoxazole is mainly used as a first-line drug for treatment and prophylaxis against Pneumocystis jiroveci pneumonia. This drug, however, has been reported as the most common causative drug for severe cutaneous adverse reactions (SCARs). This study aimed to extensively elucidate the associations between genetic polymorphisms of HLA class I and genes involved in bioactivation and detoxification of co-trimoxazole on co-trimoxazole-induced SCARS in a large sample size and well-defined Thai SCARs patients. A total of 67 patients with co-trimoxazole-induced SCARs, consisting of 51 SJS/TEN patients and 16 DRESS patients, and 91 co-trimoxazole tolerant controls were enrolled in the study. The results clearly demonstrated that the HLA-B¹13:01 allele was significantly associated with co-trimoxazole-induced SCARs, especially with DRESS (OR = 8.44, 95% CI = 2.66–26.77, P = 2.94 × 10⁻⁴, Pc = 0.0126). Moreover, the HLA-C¹08:01 allele was significantly associated with co-trimoxazole-induced SJS/TEN in the HIV/AIDS patients with an OR of 8.51 (95% CI = 2.18–33.14, P = 8.60 × 10⁻⁴, Pc = 0.0241). None of the genes involved in the bioactivation and detoxification of co-trimoxazole investigated in this study play any major role in the development of all phenotypes of SCARs.     

参附注射液治疗老年重症肺炎的疗效研究

目的探讨参附注射液对老年重症肺炎疗效及N末端B型利钠肽原(NT-pro BNP)的影响。方法选择2016年6月—2019年6月医院收治的老年重症肺炎患者80例,以随机数表法将其分为两组,即对照组与研究组各40例。对照组患者接受常规对症治疗,研究组在此基础上应用参附注射液治疗。对比两组临床疗效,治疗前与治疗3 d、5 d时血浆NT-pro BNP水平,以及不良反应情况。结果研究组治疗的总有效率为95.00%,高于对照组77.50%(P<0.05)。治疗后3 d与5 d时研究组血浆NT-pro BNP水平均低于对照组(P<0.01)。两组治疗期间均未见明显的药物不良反应。结论参附注射液能够有效提高老年重症肺炎患者的疗效,调节脑钠肽水平。     

临床护理路径用于ICU重症颅脑损伤患者护理中的价值

目的 探讨临床护理路径用于ICU重症颅脑损伤患者护理中的价值。方法 选择2017年11月～2018年10月进行ICU重症颅脑损伤治疗的患者100例作为对象,随机数字表法分为对照组(n=50)和观察组(n=50)。对照组给予常规护理,观察组在其基础上应用临床护理路径,15 d护理后比较患者依从性情况、对患者护理前后心理状态进行评分,对不良并发症产生情况进行比较。结果 观察组康复锻炼依从、按时用药依从及饮食依从高于对照组(P0.05)。护理前两组SDS与SAS评分比较差异无统计学意义(P0.05),护理后,观察组SDS与SAS评分低于对照组(P0.05)。观察组出现压疮、泌尿感染、以及发热的发生率显著低于对照组(P0.05)。结论 将临床护理路径用于ICU重症颅脑损伤患者的护理中,提高了患者的护理依从性,减少了不良情绪以及不良并发症的产生,有助于患者整体治疗,值得推广应用。     

Clinical Guidance for the Management of Patients with Urothelial Cancers During the COVID-19 Pandemic – Rapid Review

The current COVID-19 pandemic presents a substantial obstacle to cancer patient care. Data from China as well as risk models suppose that cancer patients, particularly those on active, immunosuppressive therapies are at higher risks of severe infection from the illness. In addition, staff illness and restructuring of services to deal with the crisis will inevitably place treatment capacities under significant strain. These guidelines aim to expand on those provided by NHS England regarding cancer care during the coronavirus pandemic by examining the known literature and provide guidance in managing patients with urothelial and rarer urinary tract cancers. In particular, they address the estimated risk and benefits of standard treatments and consider the alternatives in the current situation. As a result, it is recommended that this guidance will help form a framework for shared decision making with patients. Moreover, they do not advise a one-size-fits-all approach but recommend continual assessment of the situation with discussion within and between centres.     

床旁多普勒超声引导下经皮气管切开术在重症脑出血患者中的应用

目的探讨床旁多普勒超声引导下经皮气管切开术（PDT）在重症脑出血患者中的应用价值。方法选取2014年1月—2019年4月南方医科大学附属小榄医院重症医学科监护治疗的重症脑出血患者126例，在ICU床旁采用超声引导下行PDT。术前采用超声进行检查，明确气管位置、周围组织及血管情况，确定穿刺部位及深度，指导术前气管导管退管。术中实时超声引导，确保手术安全。术后超声确认气管切开套管位置，筛查排除气胸等相关并发症。观察操作时间（从皮肤穿刺到成功置入气管套管时间）、一针穿刺成功率、置管成功率、气管插管意外脱管率；观察术中及术后并发症：出血量、血管/甲状腺损伤、气管后壁损伤、皮下气肿、气胸、低氧血症发生率等。结果126例患者手术均一次操作成功，一针穿刺成功率及置管成功率均为100%，未发生气管插管意外脱管。操作时间5~12 min，平均操作时间7.5 min。术中及术后未发生难以控制的大出血、严重低氧血症、血管/甲状腺损伤、气管后壁损伤、皮下气肿及气胸等并发症。结论对重症脑出血患者行床旁实时超声引导下行PDT，提高了手术的可视性、操作性和安全性，提高PDT成功率，降低相关并发症，具有良好的临床价值。     

乌司他丁辅助治疗重症感染性休克的价值分析

目的探究临床用乌司他丁辅助治疗重症感染性休克的治疗效果。方法90例重症感染性休克患者,随机分为观察组与对照组,每组45例。对照组患者采用西医常规治疗,观察组患者在对照组基础上联合乌司他丁治疗。比较两组患者治疗效果、体温情况、感染情况以及治疗前后白细胞计数、白细胞介素-6(IL-6)水平、格拉斯哥昏迷量表(GCS)评分、急性生理功能和慢性健康状况评分系统Ⅱ(APACHEⅡ)评分。结果治疗后,观察组白细胞计数(7.34±1.32)×10^9/L低于对照组的(9.41±1.16)×10^9/L,差异具有统计学意义(P<0.05)。治疗后,观察组高热、感染体征发生率分别为97.78%、86.67%,均高于对照组的82.22%、62.22%,差异具有统计学意义(P<0.05);观察组体温恢复时间、感染消失时间分别为(7.19±1.39)、(3.88±0.89)d,均短于对照组的(9.81±1.88)、(10.76±1.57)d,差异具有统计学意义(P<0.05)。观察组患者血清IL-6为(4.27±0.95)μg/L低于对照组的(9.58±1.07)μg/L,差异具有统计学意义(P<0.05)。观察组患者GCS评分和APACHEⅡ评分较治疗前均有所改善,GCS评分(8.19±1.59)分、APACHEⅡ评分(8.83±0.82)分均优于对照组的(6.81±1.82)、(14.71±3.52)分,差异均具有统计学意义(P<0.05)。观察组患者治疗总有效率95.56%明显高于对照组的77.78%,差异具有统计学意义(χ^2=6.154,P<0.05)。结论乌司他丁具有较好的抗炎效果,与西医治疗相结合可以提高临床疗效,加快重症感染性休克患者退热速度,缩短感染时间,降低白细胞计数及血清IL-6水平,改善GCS评分和APACHEⅡ评分,临床疗效较好。     

血管紧张素转换酶2对儿童2019冠状病毒病的作用研究进展

随着严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在全球的肆虐，儿童感染者人数也越来越多。血管紧张素转换酶2（ACE2）是SARS-CoV-2感染人体的结合位点之一，可以与病毒尖峰蛋白结合，使得跨膜丝氨酸蛋白酶（TMPRSS2）启动S蛋白触发感染，引起白细胞介素-1、干扰素-γ、肿瘤坏死因子等多种炎性因子的产生。与成人相比，儿童的ACE2及TMPRSS2的表达水平较低，推测儿童症状较成人轻，发病人数较成人少均与此有关。该综述对SARS-CoV-2感染过程中ACE2的作用研究进展进行总结，有助于了解SARS-CoV-2的致病机制，为更好地开发药物及疫苗，防治儿童2019冠状病毒病提供参考。