六味地黄汤干预抑郁大鼠学习记忆的作用机制

目的:探讨六味地黄汤对慢性抑郁大鼠记忆障碍的改善作用,并探讨其可能的作用机制。方法:Wistar雌性大鼠随机分为正常组(生理盐水)、慢性不可预见性温和应激(CUMS)模型组(生理盐水)、六味地黄汤低、中、高剂量组(2. 60,7. 81,23. 50 g·kg~(-1)·d~(-1))。除正常组外,其余各组造成CUMS模型。每周称体质量,观察其行为学指标变化;实时荧光定量聚合酶链式反应(Real-time PCR)检测其海马G蛋白偶联雌激素受体(GPR30),胞内磷脂酰肌醇激酶(PI3K),环磷酸腺苷反应元件结合蛋白(CREB),脑源性神经营养因子(BDNF) mRNA的表达;酶联免疫吸附测定(ELISA)检测血清中雌激素含量。结果:与正常组比较,模型组体质量、活动能力、兴趣等明显降低(P 0. 05,P 0. 01);与模型组比较,六味地黄汤2. 60,7. 81,23. 50 g·kg~(-1)可明显提高CUMS大鼠糖水偏好度(P 0. 01)和旷场实验的站立次数(P 0. 01);7. 81,23. 50 g·kg~(-1)明显提高旷场实验的总距离(P 0. 05,P 0. 01);2. 60,7. 81 g·kg~(-1)可缩短水迷宫实验寻台潜伏期(P 0. 01);7. 81 g·kg~(-1)可增加血清中雌激素含量(P 0. 05);CUMS模型组大鼠海马组织内的GPR30,PI3K,CREB,BDNF mRNA表达明显下降(P 0. 05,P 0. 01),六味地黄汤2. 60 g·kg~(-1)显著增加海马组织内的GPR30,CREB mRNA表达(P 0. 05,P 0. 01),7. 81 g·kg~(-1)明显增加海马组织内的GPR30,PI3K,CREB,BDNF mRNA表达量(P 0. 05,P 0. 01)。结论:六味地黄汤具有抗抑郁作用,逆转CUMS大鼠抑郁样行为及学习记忆障碍,其中中剂量组药效最显著。其作用机制可能与增加血清中雌激素和提高大鼠海马GPR30,PI3K,CREB,BDNF mRNA表达有关。     

Comparison of survival between adolescent and young adult vs older patients with hepatocellular carcinoma

BACKGROUNDDue to the special clinical features and biologic characteristics of adolescent and young adult (AYA) cancers, AYA cancers are different from cancers in children and elderly individuals. However, there are few reports on AYA hepatocellular carcinoma (HCC).AIMTo investigate the overall survival (OS) of AYA (15-39 years) and elderly (40-74 years) patients with HCC.METHODSThe data of all the HCC cases were extracted from the Surveillance, Epidemiology, and End Results database from 2004 to 2015 and were then divided into two groups based on age: AYA group (15-39 years) and older group (40-74 years). Kaplan-Meier curves and log-rank tests were used to compare the OS of the two groups. Propensity score matching (PSM) was employed to analyze the OS difference between the two groups. The Cox proportional hazards regression model was used to perform multivariate analysis to explore the risk factors for OS of HCC patients.RESULTSCompared to elderly cancer patients, AYA patients with HCC had a worse Surveillance, Epidemiology, and End Results stage, including the distant stage (22.1% vs 15.4%, P < 0.001), and a more advanced American Joint Committee on Cancer (AJCC) stage, including AJCC III and IV (49.2% vs 38.3%, P < 0.001), and were more likely to receive surgery (64.5% vs 47.5%, P < 0.001). Before PSM, the AYA group had a longer survival in months (median: 20.00, interquartile range [IQR]: 5.00-62.50) than the older group (median: 15.00, IQR: 4.00-40.00) (P < 0.001). After PSM, the AYA group still had a longer survival in months (median: 21.00, IQR: 5.00-64.50) than the older group (median: 18.00, IQR: 6.00-53.00) (P < 0.001). The Cox proportional hazards regression model showed that advanced age (hazard ratio [HR] = 1.405, 95%CI: 1.218-1.621, P < 0.001) was a risk factor for OS of HCC patients. In the subgroup analysis, the Cox proportional hazards regression model showed that in AJCC I/II HCC patients, advanced age (HR = 1.749, 95%CI: 1.352-2.263, P < 0.001) was a risk factor for OS, while it was not a risk factor in AJCC III/IV HCC patients (HR = 1.186, 95%CI: 0.997-1.410, P = 0.054) before PSM. After PSM, advanced age (HR = 1.891, 95%CI: 1.356-2.637, P < 0.001) was still a risk factor for OS in AJCC I/II HCC patients, but was not a risk factor for OS in AJCC III/IV HCC patients (HR = 1.192, 95%CI: 0.934-1.521, P = 0.157) after PSM.CONCLUSIONAYA patients with HCC have different clinical characteristics from older adults. In different AJCC stages, the two groups of patients have different OS: In AJCC I/II HCC patients, advanced age is a risk factor for OS, but it is not a risk factor for OS in the AJCC III/IV HCC patient group.     

First‐in‐human phase I study of E7090, a novel selective fibroblast growth factor receptor inhibitor,in patients with advanced solid tumors

Fibroblast growth factor receptors (FGFR) are a family of transmembrane receptor tyrosine kinases involved in regulating cellular processes. FGFR mutations are implicated in oncogenesis, representing therapeutic potential in the form of FGFR inhibitors. This phase I, first‐in‐human study in Japan evaluated safety and tolerability of E7090, a potent selective FGFR1‐3 inhibitor, in patients with advanced solid tumors. Dose escalation (daily oral dose of 1‐180 mg) was carried out to assess dose‐limiting toxicity (DLT), maximum tolerated dose, and pharmacokinetics. Pharmacodynamic markers (serum phosphate, fibroblast growth factor 23, and 1,25‐(OH)₂‐vitamin D) were also evaluated. A total of 24 patients refractory to standard therapy or for whom no appropriate treatment was available were enrolled. No DLT were observed up to the 140‐mg dose; one patient in the 180‐mg cohort experienced a DLT (increased aspartate aminotransferase/alanine aminotransferase, grade 3). The maximum tolerated dose was not reached. Dose‐dependent increases in the maximum concentration and area under the curve from time 0 to the last measurable concentration were observed up to 180 mg. Dose‐dependent increases were observed in all pharmacodynamic markers and plateaued at 100‐140 mg, indicating sufficient FGFR pathway inhibition at doses ≥100 mg. In conclusion, E7090 showed a manageable safety profile with no DLT at doses ≤140 mg. Maximum tolerated dose was not determined. The recommended dose for the follow‐up expansion part, restricted to patients with tumors harboring FGFR alterations, was determined as 140 mg, once daily.     

基于网络药理学的中期诊疗方干预新型冠状病毒肺炎(COVID-19)作用机制研究

目的通过网络药理学方法研究新型冠状病毒肺炎(COVID-19)中期诊疗方(XGZQZLF)治疗COVID-19的作用机制。方法采用网络药理学方法,以中药系统药理学数据库、GeneCards数据库等为支撑,通过Cytoscape构建"药物-活性成分-靶点-疾病"网络,进一步进行基因富集分析和通路注释,研究XGZQZLF治疗COVID-19的物质基础和作用机制。结果筛选出XGZQZLF有效成分80个,通过调控蛋白激酶(AKT1)、白细胞介素6(IL-6)、丝裂原活化蛋白激酶3(MAPK3)、血管内皮生长因子A(VEGFA)、半胱氨酸蛋白酶3(CASP3)等208个肺炎相关靶点,以及主要通过调控TNF信号通路、IL-17信号通路、Th17细胞分化、缺氧诱导因子1(HIF-1)信号通路等炎症和免疫相关通路发挥治疗COVID-19的作用。结论 XGZQZLF通过多成分、多靶点、多通路协同作用发挥治疗COVID-19的作用,为XGZQZLF治疗COVID-19的生物机制研究提供数据支撑,同时为COVID-19药物研发提供参考。     

靶向沉默髓鞘转录因子MyT1对脑胶质瘤细胞恶性生物学行为的影响

目的 探讨靶向沉默髓鞘转录因子1（MyT1）对人脑胶质瘤细胞迁移、侵袭和黏附的影响和相关分子机制。方法 设计特异性靶向沉默MyT1基因的shRNA，包装慢病毒后感染人脑胶质瘤U-118MG和U-87MG细胞，qPCR和Western blot检测两种细胞中MyT1的表达水平，BrdU实验、细胞划痕实验、Transwell实验和细胞黏附实验分别检测两种细胞的迁移、侵袭和黏附能力的变化，qPCR检测细胞黏附和肿瘤转移相关基因的表达水平。结果 在HEK293T细胞中包装了特异性靶向MyT1基因的shRNA慢病毒，并成功感染了U-118MG和U-87MG细胞；两种细胞中MyT1 mRNA和蛋白表达水平均显著下调（均P<0.05），细胞的迁移、侵袭和黏附能力均有一定程度的降低（均P<0.05），细胞黏附相关基因表达水平显著下降，肿瘤转移相关基因表达水平显著上升（均P<0.05）。结论 靶向沉默MyT1基因对人脑胶质瘤U-118MG和U-87MG细胞的迁移、侵袭和黏附能力有抑制作用，其机制可能与调控细胞黏附和肿瘤转移相关基因的表达有关。MyT1基因的表达，可能是脑胶质瘤诊疗的一个潜在靶标。     

肾炎方联合缬沙坦分散片对慢性肾小球肾炎患者的疗效与肾功能的影响

目的:探究肾炎方联合缬沙坦分散片治疗慢性肾小球肾炎患者的疗效及对肾功能的影响。方法:选取2016年2月至2019年2月重庆医科大学附属一医院合川医院肾脏内科收治的慢性肾小球肾炎患者122例作为研究对象,随机分为对照组和观察组,每组61例。对照组患者采用下缬沙坦分散片治疗,观察组在对照组基础上采用自拟肾炎方与缬沙坦分散片联合治疗,分析比较2组患者的肾功能指标的动态变化、炎性因子的表达水平、临床疗效及治疗后不良反应。结果:治疗后观察组TC、TG、BUN、Scr及24 hUPE5项指标的动态变化均低于对照组,差异有统计学意义(P<0.05),且观察组ALB动态变化高于对照组,差异有统计学意义(P<0.05);治疗后观察组IL-6、IL-10、CRP及TNF-α水平明显低于对照组,差异有统计学意义(P<0.05),观察组治疗有效率(98.4%)优于对照组(86.9%),差异有统计学意义(P<0.05);观察组不良反应发生率(6.6%)低于对照组(31.1%),差异有统计学意义(P<0.05)。结论:采用自拟肾炎方与缬沙坦分散片联合的治疗方案可增强疗效,提升肾功能,降低促炎性因子的表达水平及不良反应,值得在临床中推广普及。     

针刺足运感区结合局部电针围刺治疗中风后尿失禁的临床观察

[目的]观察针刺足运感区结合局部电针围刺与常规针刺、常规针刺联合足运感区治疗中风后尿失禁的临床疗效差异。[方法]将90例患者随机分为治疗组、对照1组和对照2组,每组30例,治疗组予针刺足运感区结合膀胱体表相应投影区域电针围刺;对照1组参照全国高等中医药院校"十三五"规划教材《针灸治疗学》中有关"尿失禁"的治疗选穴;对照2组在对照1组的基础上联合足运感区针刺,每日上午行神经内科常规治疗,每日下午行中风后尿失禁的临床治疗,每次30 min,每周连续治疗6次,6次为1个疗程,疗程间休息1 d,共2个疗程。观察3组治疗前后尿失禁程度、尿失禁临床症状评分及日常生活活动能力量表(ADL)评分,并比较3组患者的临床疗效。[结果] 3组患者治疗后尿失禁程度、尿失禁临床症状评分及ADL评分均较前改善(均P0.05),治疗组对尿失禁程度及尿失禁临床症状评分的改善较其他两组更明显(P0.05),且治疗组和对照2组的ADL评分明显优于对照1组(P0.05)。治疗组总有效率为93.3%(30/28),优于对照1组76.7%(30/23)和对照2组83.3%(30/25,P0.05)。[结论]针刺足运感区结合局部电针围刺治疗中风后尿失禁疗效显著。     

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。     

解毒化浊促愈汤联合美沙拉嗪肠溶片治疗溃疡性结肠炎的疗效及对炎性细胞因子的影响

目的:研究解毒化浊促愈汤治疗溃疡性结肠炎的疗效及对白细胞介素-6(Interleukin-6,IL-6)、肿瘤坏死因子(Tumor Necrosis Factor-alpha,TNF-α)水平的影响。方法:选取自2017年8月-2018年10月在河南省中医院肛肠科就诊的溃疡性结肠炎患者60例为研究对象,随机将分为观察组与对照组,每组各30例。对照组用美沙拉嗪治疗,观察组在对照组治疗基础上联合解毒化浊促愈汤治疗。两组均连续治疗6周,比较两组患者治疗后的临床疗效以及治疗前后的IL-6、TNF-α水平变化情况。结果:治疗后观察组临床症状明显改善,总有效率为93.3%(28/30),明显高于对照组的70.0%(21/30)。治疗后,两组患者的血清IL-6、TNF-α水平分别较治疗前显著降低(P<0.05),且观察组各指标水平均低于对照组,差异显著(P<0.05)。结论:此方治疗方法能够明显缓解患者的临床症状,抑制炎症反应,提高临床疗效,具有临床推广价值。     

基于“祛邪为第一要义”从清热化湿论治新型冠状病毒肺炎

结合验案分析,基于"祛邪为第一要义"探讨新型冠状病毒肺炎从清热化湿论治的思路与方法。认为新型冠状病毒肺炎主要是属于"湿热"性质的疫病,治疗应强调清热化湿,以"祛邪为第一要义",辅以扶正。在中医祛邪与扶正理论指导下,通过宣肺平喘、通腑泻热、芳香化湿等治法,祛邪为主,肺肠合治,可以使发热减轻或消退,使大便通畅,从而截断病情进展,避免或减少危重症的发生及死亡的风险;通过清热化湿、疏肝健脾、凉血化瘀等治法,祛邪兼以扶正,肺与肝、脾合调,可以改善肝功能损伤,减少病情加重的风险;通过补气健脾等扶正治法,可以改善患者的精神和体力,促使病毒更快转阴,缩短病程,促进患者早日康复。