Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors

Microsatellite instability-high (MSI-H) and tumor mutational burden (TMB) are predictive biomarkers for immune-checkpoint inhibitors (ICIs). Still, the relationship between the underlying cause(s) of MSI and TMB in tumors remains poorly defined. We investigated associations of TMB to mismatch repair (MMR) protein expression patterns by immunohistochemistry (IHC) and MMR mutations in a diverse sample of tumors. Hypothesized differences were identified by the protein/gene affected/mutated and the tumor histology/primary site. Overall, 1057 MSI-H tumors were identified from the 32 932 tested. MSI was examined by NGS using 7000+ target microsatellite loci. TMB was calculated using only nonsynonymous missense mutations sequenced with a 592-gene panel; a subset of MSI-H tumors also had MMR IHC performed. Analyses examined TMB by MMR protein heterodimer impacted (loss of MLH1/PMS2 vs. MSH2/MSH6 expression) and gene-specific mutations. The sample was 54.6% female; mean age was 63.5 years. Among IHC tested tumors, loss of co-expression of MLH1/PMS2 was more common (n = 544/705, 77.2%) than loss of MSH2/MSH6 (n = 81/705, 11.5%; P < .0001), and was associated with lower mean TMB (MLH1/PMS2: 25.03 mut/Mb vs MSH2/MSH6 46.83 mut/Mb; P < .0001). TMB also varied by tumor histology: colorectal cancers demonstrating MLH1/PMS2 loss had higher TMBs (33.14 mut/Mb) than endometrial cancers (20.60 mut/Mb) and other tumors (25.59 mut/Mb; P < .0001). MMR gene mutations were detected in 42.0% of tumors; among these, MSH6 mutations were most common (25.7%). MSH6 mutation patterns showed variability by tumor histology and TMB. TMB varies by underlying cause(s) of MSI and tumor histology; this heterogeneity may contribute to differences in response to ICI.     

养阴益气活血汤对慢性心力衰竭患者心功能及生活质量的影响

目的:研究养阴益气活血汤对慢性心力衰竭患者心功能和生活质量的影响。方法:将慢性心力衰竭患者86例随机分为2组。对照组采用常规西药治疗,观察组联合养阴益气活血汤治疗。观察比较2组左心室射血分数(LVEF)、左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、生活质量评分、中医证候积分、疗效和不良反应。结果:治疗后,2组LVEF升高,LVEDD、LVESD降低,且观察组LVEF高于对照组,LVEDD、LVESD低于对照组,差异有统计学意义(P<0.05)。治疗后,2组中医证候积分、生活质量评分均降低,且观察组中医证候积分、生活质量评分低于对照组,差异有统计学意义(P<0.05)。观察组总有效率为93.02%,对照组总有效率为76.74%,观察组总有效率高于对照组(P<0.05)。结论:养阴益气活血汤治疗慢性心力衰竭,能显著改善患者心功能,提高生活质量,安全可靠。     

扶正化痰固本方对早期非小细胞肺癌术后患者免疫功能的影响

目的:观察扶正化痰固本方运用于早期非小细胞肺癌术后的临床疗效及其对患者免疫功能的影响。方法:将70例早期非小细胞肺癌患者按照随机数字表法分为对照组和观察组,每组各35例。两组患者均接受肺癌切除术治疗,对照组术后3周开始接受MVP方案化疗,观察组在对照组的基础上加用扶正化痰固本方治疗。比较两组患者的临床疗效及治疗前后中医证候积分、卡氏评分(karnofsky performance status,KPS)及生活质量评分变化情况。检测两组患者治疗前后免疫功能指标、血清肿瘤标志物[癌胚抗原(carcinoembryonic antigen,CEA)、糖类抗原153(carbohydrate antigen 153,CA153)]水平。结果:观察组有效率为91.43%,对照组有效率为71.43%,两组患者有效率比较,差异具有统计学意义(P<0.05)。两组患者治疗后中医证候积分低于本组治疗前,且观察组治疗后低于对照组治疗后,差异具有统计学意义(P<0.05)。两组患者治疗后免疫功能指标检测结果低于本组治疗前,且观察组治疗后低于对照组治疗后,差异具有统计学意义(P<0.05)。两组患者治疗后血清CEA、CA153水平低于治疗前,KPS评分、QLQ-C30评分均高于治疗前,且观察组治疗后血清CEA、CA153水平低于对照组,KPS评分、QLQ-C30评分均高于对照组,差异具有统计学意义(P<0.05)。观察组胃肠道反应及骨髓抑制发生率均低于对照组,差异具有统计学意义(P<0.05)。结论:扶正化痰固本方运用于早期肺癌术后,能够有效改善患者免疫功能,减轻毒副反应,提高患者生活质量。     

OSAHS患儿扁桃体和腺样体术后免疫功能的变化

目的 阻塞性睡眠呼吸暂停低通气综合征(OSAHS)是耳鼻咽喉科的一种常见病，儿童发病率呈上升趋势，调查显示儿童OSAHS发生率为4%~5%，2~6岁是发病的高峰期。OSAHS不仅严重影响儿童的睡眠质量，还会引起儿童生长发育迟缓、智力缺陷等一系列不良反应，OSAHS患儿的主要病因是扁桃体和/或腺样体肥大，因此最有效的治疗方法是扁桃体切除术和腺样体切除术。而扁桃体和腺样体是儿童淋巴组织系统的重要组成部分，在机体的防御和保护功能中发挥着重要作用。手术治疗OSAHS是否影响儿童的免疫功能目前存在争议。一些学者认为扁桃体切除和腺样体切除后儿童的免疫力降低，而另一些学者认为OSAHS儿童的免疫力在手术后保持不变，甚至比手术前有所提高。本文就儿童OSAHS手术前后免疫指标的变化作一综述。     

Variables associated with subjective cognitive change among Iraq and Afghanistan war Veterans with blast-related mild traumatic brain injury

Introduction: This study investigated variables associated with subjective decline in executive function among Veterans of Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND) following a history of blast-related mild traumatic brain injury (mTBI).

Method: Fifty-six male U.S. Veterans (M_Age = 35.3 ± 8.8 years) with a history of blast-related mTBI (6.6 ± 3.2 years post injury) completed a battery of self-report questionnaires and neuropsychological measures. Participants rated current and retrospectively estimated pre-mTBI executive function difficulties on the Frontal Systems Behavior Scale (FrSBe). A difference score (post- minus pre-mTBI ratings) was the dependent variable (?FrSBe). Linear regression models examined variables predicting ?FrSBe, including: pre-injury characteristics (education, premorbid intelligence), injury-related characteristics (number of blast exposures, losses of consciousness), post-injury clinical symptoms (PTSD Checklist–Military version; Pittsburgh Sleep Quality Index), and post-injury neuropsychological performances on executive function measures (Trail Making Test Part B; Controlled Oral Word Association Test; Auditory Consonant Trigrams; Wisconsin Card Sorting Test).

Results: While 11% of participants had a clinically elevated pre-injury FrSBe total score, 82% had a clinically elevated post-injury FrSBe total score. Only self-reported PTSD symptom severity independently predicted perceived change in executive function.

Conclusions: Many OEF/OIF/OND Veterans with a history of blast-related mTBI experience subjective decline in executive function following injury. Perceived executive function decline was associated with higher PTSD symptom severity, aligning with previous research associating PTSD with cognitive complaints. Results did not support a correspondence between perceived cognitive change and neuropsychological performances.     

重型/危重型新型冠状病毒肺炎机械通气患者的肺康复策略

结合国内外中西医肺康复的研究成果,探讨重型/危重型新型冠状病毒肺炎机械通气患者的肺康复策略。机械通气是治疗重型/危重型肺炎必不可少的支持手段,但可能引起呼吸肌无力,导致痰液排泄障碍,进而影响预后。对于重型/危重型新型冠状病毒肺炎机械通气患者而言,及早采取必要的中西医肺康复干预措施意义重大,不仅有助于缓解呼吸困难症状,而且可缩短住院时间、改善预后。     

化瘀解毒汤对脓毒血症APACHEⅡ评分、ISTH DIC评分及外周血树突状细胞表面物质表达水平的影响

目的探讨化瘀解毒汤对脓毒血症患者APACHEⅡ评分、ISTH DIC评分及外周血树突状细胞表面物质表达水平的影响。方法将66例脓毒症患者随机分为对照组和化瘀解毒组,每组33例。对照组给予抗感染、补充血容量、积极治疗原发疾病、吸氧等综合治疗,化瘀解毒组在上述基础上加用化瘀解毒汤治疗,每日1剂,持续治疗2周。检测血清炎症因子[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、降钙素原(PCT)]水平变化,应用急性生理与慢性健康状况评分Ⅱ(APACHEⅡ)、DIC评分评估脓毒症患者病情严重程度,应用流式细胞仪分析树突状细胞相关表面分子CD80、CD83、CD86表达情况,比较临床疗效。结果与治疗前比较,两组血清IL-6、TNF-α、PCT水平均降低(P<0.01),APACHEⅡ评分、ISTH DIC评分均降低(P<0.01),CD80、CD86水平均降低(P<0.01),CD83水平无差异(P>0.05);与对照组比较,化瘀解毒组血清IL-6、TNF-α、PCT水平均较低(P<0.01),APACHEⅡ评分、ISTH DIC评分均较低(P<0.01),CD80、CD86水平均较低(P<0.01),总有效率较高(P<0.01)。结论化瘀解毒汤辅助治疗脓毒血症疗效显著,可有效降低APACHEⅡ评分、ISTH DIC评分,可能与调节外周血树突状细胞表面物质表达有关。     

腮腺切除术中沿面神经总干顺行解剖面神经的效果及安全性

目的探讨腮腺切除术中应用沿面神经总干顺行解剖面神经的治疗效果及安全性。方法选取我院2016年2月至2019年3月收治的60例择期行腮腺切除术的患者,随机分为观察组与对照组各30例。对照组沿面神经总干逆行解剖面神经,观察组沿面神经总干顺行解剖面神经,观察两组患者术后1个月面神经功能及术后并发症发生情况。结果术后1个月,两组患者的面神经功能分级比较无统计学差异(P>0.05);观察组的术后并发症发生率为10.00%,明显低于对照组的33.33%(P <0.05)。结论临床行腮腺切除术中,沿面神经总干顺行解剖面神经可降低术后并发症发生率,值得推广。