Stratification of HPV-associated and HPV-negative oropharyngeal squamous cell carcinomas based on DNA methylation epigenotypes

While the incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing in these two decades, primarily due to human papillomavirus (HPV), stratification of OPSCC into molecular subgroups showing different clinicopathological features has not been fully investigated. We performed DNA methylome analysis using Infinium 450k for 170 OPSCC cases, including 89 cases in our cohort and 81 cases reported by The Cancer Genome Atlas, together with targeted exon sequencing analysis. We stratified OPSCC by hierarchical clustering analysis using methylome data. Methylation levels of classifier markers were validated quantitatively using pyrosequencing, and area under the curve (AUC) values of receiver operating characteristics (ROC) curves were calculated. OPSCC was stratified into four epigenotypes: HPV(+) high-methylation (OP1), HPV(+) intermediate-methylation (OP2), HPV(−) intermediate-methylation (OP3) and HPV(−) low-methylation (OP4). Ten methylation marker genes were generated: five to classify HPV(+) cases into OP1 and OP2, and five to classify HPV(−) cases into OP3 and OP4. AUC values of ROC curves were 0.969 and 0.952 for the two marker panels, respectively. While significantly higher TP53 mutation and CCND1 copy number gains were observed in HPV(−) than in HPV(+) groups (p < 0.01), no significant difference of genomic aberrations was observed between OP1 and OP2, or OP3 and OP4. The four epigenotypes showed significantly different prognosis (p = 0.0006), distinguishing the most favorable OPSCC subgroup (OP1) among generally favorable HPV(+) cases, and the most unfavorable OPSCC subgroup (OP3) among generally unfavorable HPV(−) cases. HPV(+) and HPV(−) OPSCC are further divided into distinct DNA methylation epigenotypes, showing significantly different prognosis.     

从五运六气角度探析己亥年冬瘟

2019年为己亥之年,土运不足,厥阴风木司天,少阳相火在泉。下半年相火淫胜,火气流行,克金、刑水。风木盛则克制土运,土运本不足,致虚者更虚,强者更强,此谓之不相得,不相得则病;且气克运,古称之为天刑,天刑之年多灾害。2019年,冬季主气太阳寒水之上少阳相火客临,致冬不藏反长,天不寒反暖。地气封藏不固,水中阳气不藏,本应该被抑制或杀灭的微生物却因火热而未灭,并得少阳火毒助长而毒性更猛,化生为火疫。2020年为庚子年,主行金运,金克木,可平复2019年偏盛之木运,故瘟毒会被2020年之金运削弱或肃杀。针对此次瘟疫,未病之人预防要点为:虚邪贼风,避之有时;精神内守,病安从来;正气存内,邪不可干;饮食宜忌,尤为重要;避秽化浊,芳香化湿。已病之人的治疗,依据此次瘟疫"少阳火毒夹湿"病机,以咸补之,以甘泻之,以咸耎之,岁谷宜丹,间谷宜豆。此次瘟毒的性质虽为湿热火毒,但患者体质却有寒热虚实之别,感染后症状、病情和预后亦不同,故中医临证时应遵循辨证论治,三因治宜的原则;若体质素有湿热,邪从本气而化,可遵循运气病机施治;若体质本热,湿去而化为火毒,则应以制火为主;若体质本寒,热去而化寒湿,则应温化寒湿,芳香化浊;若体质素虚,出现危重证候,则应在祛邪时,重视固护元气。     

“透法”在外感热病中的运用

外感之邪从口鼻、皮毛侵袭人体,肺卫首先受邪。在外感病初期,肺卫失宣是病机的关键,治疗应重在宣通肺卫。外感风寒邪气,寒邪直接损伤卫阳,郁遏肺气,治当辛温解表。外感风热邪气,阳邪郁遏气机,损伤津液,易化燥化火,甚则内陷生变,治当辛凉解表。湿热邪气从口鼻、皮毛而入,初起即表现为卫气同病,治当宣化表里湿热。燥气为病,易伤肺脏、耗津液,与热相合则易化热化火,而成温燥,治宜辛凉甘润。外感热病初起,六淫邪气侵袭肺卫,气机郁滞,进而津停成饮、成痰;气有余便是火,郁滞之气化燥化火,甚则动血。治疗总则为宣通气机,此即"透法"之运用。故在外感热病初起的治疗中,贵在把握气机状态,让肺卫之气宣畅,正气宣布,则邪气潜消。     

通脉降脂饮对痰瘀互阻型动脉粥样斑块稳定性的影响

目的:观察通脉降脂饮治疗痰瘀互阻型动脉粥样硬化患者的临床疗效,探讨通脉降脂饮干预动脉粥样硬化斑块稳定性的可能机制。方法:选取2018年1-12月在佛山市禅城区人民医院门诊就诊或健康体检的急性心脑血管事件后2周的患者175例,随机分为对照组86例和观察组89例,对照组口服阿司匹林肠溶片、辛伐他汀分散片治疗,观察组在对照组治疗的基础上加服通脉降脂饮,日1剂,两组疗程均为6个月。观察两组患者临床疗效及相关指标变化情况。结果:对照组有效率为83.72%,观察组有效率为93.26%,两组有效率比较,差异有统计学意义(P<0.05)。两组患者治疗前血清超敏C反应蛋白(hypersensitive C-reactive protein,hs-CRP)、金属基质蛋白酶9(Matrix metalloproteinase 9,MMP-9)、血同型半胱氨酸(homocysteine,Hcy)比较,差异无统计学意义(P>0.05)。治疗后两组血清Hs-CRP、MMP-9、Hcy与治疗前比较,差异有统计学意义(P<0.05);两组急性心脑血管事件后血清Hs-CRP、MMP-9、Hcy与治疗前比较,差异有统计学意义(P<0.05);急性心脑血管事件后血清Hs-CRP、MMP-9、Hcy组间比较,差异有统计学意义(P<0.05)。对照组急性心脑血管事件发生率为23.26%,治疗组急性心脑血管事件发生率为11.24%,两组急性心脑血管事件发生率比较,差异有统计学意义(P<0.05)。两组均未发生死亡、肝肾异常等病例。结论:通脉降脂饮可以降低动脉粥样硬化患者血清Hs-CRP、MMP-9、Hcy,减少急性心脑血管事件的发生。     

益气补血化瘀汤治疗冠心病心绞痛临床研究

目的:观察益气补血化瘀汤治疗冠状动脉粥样硬化性心脏病(简称冠心病)心绞痛的临床疗效。方法:选取本院2018年1月诊治的冠心病心绞痛患者80例作为研究对象,按照双盲筛选法分为对照组与观察组,每组40例。对照组给予常规西药治疗,观察组给予自拟益气补血化瘀汤治疗。结果:观察组有效率为95.0%,对照组有效率为80.0%,两组有效率比较,观察组高于对照组,差异有统计学意义(P<0.05);治疗后,观察组患者血液黏稠度、血管阻力均低于对照组,血管弹性高于对照组,差异有统计学意义(P<0.05);观察组治疗后心绞痛持续时间、发作次数、心绞痛积分均低于对照组,差异有统计学意义(P<0.05);对照组不良反应发生率为60.0%,观察组不良反应发生率为15.0%,观察组低于对照组,差异有统计学意义(P<0.05)。结论:益气补血化瘀汤治疗冠心病心绞痛可改善血液黏稠度、血管阻力、血管弹性,降低心绞痛持续时间、发作次数、心绞痛积分,且不良反应发生率低。     

A Phase II Study of Midostaurin and 5-Azacitidine for Untreated Elderly and Unfit Patients With FLT3 Wild-type Acute Myelogenous Leukemia

BackgroundMidostaurin, a multikinase inhibitor, is approved for treatment of FLT3-mutant acute myeloid leukemia (AML). A phase I study established that midostaurin 75 mg orally twice daily for 14 days with standard dose azacitidine was safe and tolerable in elderly patients with AML. Herein, we report the phase II expansion cohort of previously untreated elderly or unfit patients with AML.Patients and MethodsPrimary objectives were to further describe the toxicity profile and determine the response rate in untreated patients with AML. Patients received midostaurin 75 mg orally twice daily on days 8 to 21 in combination with intravenous azacitidine at 75 mg/m² on days 1 to 7. Plasma inhibitory activity assay for FLT3 was performed pretreatment and on day 8 and day 15 of each cycle.ResultsTwenty-six patients (median age, 74 years; range, 59-85 years) with FLT3 wild-type AML were accrued. Patients received a median of 2 cycles of therapy (range, 1-10 cycles). Seven (29%) of 24 evaluable patients achieved a clinical response (4 complete response; 1 complete response with incomplete count recovery; and 2 partial response). The median overall survival was 244 days (95% confidence interval, 203-467 days). Hematologic, infectious, and gastrointestinal toxicities were comparable to similar studies. Peripheral blood FLT3 wild-type phosphorylation declined to 8% to 55% of pretreatment by day 15 of cycle 1 (7 patients) and declined with subsequent cycles (< 10% baseline) in 2 patients who were analyzed after cycle 3.ConclusionMultiple cycles of azacitidine and midostaurin were not well-tolerated, but persistent inhibition of FLT3 wild-type phosphorylation suggest intermittent dosing of midostaurin should be considered in future low-intensity regimens for FLT3-mutant AML.     

基于“凡土脏取决于胆”议从胆论治阿尔茨海默病

阿尔茨海默病(Alzheimer’s Disease,AD)归属于中医"痴呆""呆病""健忘"等范畴,历代医家认为此病多以肾精失养,髓海空虚为主要病机,治疗多从脾、肾两脏着手,鲜有提及从胆论治。从中医学"凡土脏取决于胆"理论切入,以土脏与AD发病的关系为着眼点,并结合胆内藏精汁,助脾胃腐熟运化水谷;胆主升清降浊,疏利中土;胆内寄相火,参与腐熟水谷的生理功能和特性,阐述从胆论治AD的理论基础,以期为中医临床更加有效的防治阿尔茨海默病提供参考。     

干扰素联合炎琥宁治疗小儿手足口病的临床效果评价

目的 探究干扰素联合炎琥宁治疗小儿手足口病的效果观察.方法 选取2016年4月—2019年3月医院收治的手足口病患儿104例,依随机数字表分为参照组和干预组,各52例.参照组患儿应用干扰素治疗,干预组患儿加用炎琥宁治疗.观察两组患儿的治疗效果、临床症状消退时间、黏附分子表达量和心肌酶水平.结果 干预组患儿治疗总有效率为90.38%,明显高于参照组患儿的75%;干预组患儿发热、口腔溃疡和手足皮疹的消退时间均明显短于参照组患儿(P<0.05);两组患儿治疗后的CD44、ICAM-1、VCAM-1、CK、LDH和CK-MB水平均明显低于治疗前水平(P<0.05),且干预组患儿治疗后的CD44、ICAM-1、VCAM-1、CK、LDH和CK-MB水平均明显低于参照组患儿治疗后水平(P<0.05).结论 干扰素联合炎琥宁治疗小儿手足口病的效果显著.