Liquid biopsy is a valuable tool in the diagnosis and management of lung cancer

Liquid biopsy refers to the use of various body fluids to test for circulating biological elements derived from the tumor. Liquid biopsy has taken on an increasingly important role in lung cancer diagnosis, molecular characterization, surveillance, monitoring, and determining mechanisms of resistance. These assays can utilize various sources of cell-free DNA (cfDNA) including blood, pleural fluid, urine, and others to detect tumor associated alterations. With the increasing power of next-generation sequencing technologies and the development of assays such as digital droplet PCR, rare tumor alleles can be detected in cfDNA to determine key characteristics of the tumor. Current assays, while effective, are still challenged by limited sensitivity and capacity to single genes or small panels of genes, though this is rapidly expanding. Nevertheless, testing of cfDNA has been shown to be valuable in detecting resistance to targeted inhibitors, particularly for detection of T790M in EGFR and monitoring response to therapy. With the continued development of more powerful and sensitive assays, these techniques will empower clinicians to better characterize early stage disease and can be used in the screening of high-risk patients, which may eliminate the requirement for tissue diagnosis in some settings. That said, since the majority of these alterations are not specific to lung cancer, there will continue to be a need for tissue in at least the initial diagnosis. Used in conjugation with tissue sampling, these assays will assist the treating clinician and the pathologist to better characterize individual tumors, even in the setting of limited tissue.     

Different metabolic profiles of K1 serotype and non-serotype K1 and K2 Klebsiella pneumoniae isolates in oral infection mice model

K1 or K2 serotype Klebsiella pneumoniae isolate caused clinical pyogenic liver abscess (KLA) infection is prevalent in many areas. It has been identified that K1 or K2 serotype K. pneumoniae isolates caused KLA infection in mice by oral inoculation. In our study, K1 serotype K. pneumoniae isolate Kp1002 with hypermucoviscosity (HV)-positive phenotype caused KLA infection in C57BL/6 mice by oral inoculation. Simultaneously, non-serotype K1 and K2 isolate Kp1014 with HV-negative phenotype failed to cause KLA infection in the same manner. It seems that gastrointestinal tract translocation is the pathway by which K1 or K2 serotype K. pneumoniae caused KLA infection. Liquid chromatography-tandem mass spectrometry was used to further analyze metabolic profile changes in mice with KLA infection. Data showed that after Kp1002 or Kp1014 oral inoculation, serum Phosphatidylcholine (PC) and Lysophosphatidylcholine (LPC) levels significantly changed in mice. Some PC and LPC molecules showed changes both in the Kp1002 KLA group and the Kp1014 no-KLA group compared with the control group. The level of 18:1/18:2-PC significantly changed in the Kp1002 KLA group compared with the control group, but showed no change between the Kp1014 no-KLA group and the control group. The level of 18:1/18:2-PC might have been particularly affected by KLA infection caused by K1 serotype K. pneumoniae Kp1002. It may be a potential biomarker for KLA infection.     

Thyroid hormonal profile in elderly patients treated with two different levothyroxine formulations: A single institute survey

PurposeRecent evidences suggest that, despite the large use of levothyroxine (L-T4), up to 40% of patients are over-treated developing sub-clinical hyperthyroidism. We compared TSH, fT4 and fT3 serum levels of elderly patients in treatment with liquid and tablet L-T4 formulations over a period of time of five years.SubjectsPatients were recruited by searching the database of those treated and followed at the Thyroid Unit of the University of Brescia.ResultsTwo hundred and ninety-nine patients (251 females, 48 males) were treated with L-T4 in tablet form (group T) and 118 subjects (107 female, 11 male) with liquid LT4 (group L). The two groups were super-imposable by age, median L-T4 dosage, TSH, fT4 and fT3 values. A slightly but not significantly higher BMI value was observed among patients of group L over those of group T (26.9 ± 2.9 vs. 26.4 ± 2.1 kg/cm², respectively). During five years of LT-4 treatment, sub-clinical or over-hypothyroidism was found in 13 (4.3%) and 3 (2.5%) patients of group T and group L (P = 0.335), whereas, subclinical or clinical hyperthyroidism was significantly more frequent among patients of group T than those of group L [69 (23%) vs. 5 (4.2%) patients, (P = 0.0001)]. Logistic regression analysis showed that only the Tablets were associated with the risk of developing subclinical or hyperthyroidism [OR 2·354 (1·136–4·827), P = 0.021].ConclusionsWe show a greater stability in the thyroid profile of hypothyroid elderly patients in treatment with liquid thyroxine as opposed to those being treated by tablet formulation over five years of follow-up.     

内源性大麻素及其代谢酶与孤独症谱系障碍严重程度的相关性

目的探讨内源性大麻素(endocannabinoid,eCB)及其代谢酶与孤独症谱系障碍(autism spectrum disorder,ASD)的关联,为ASD的病因及发病机制研究提供理论依据。方法采用病例对照的研究方法,收集2017年6月至2018年12月在哈尔滨医科大学儿童发育行为研究中心就诊和在省孤独症定点康复机构接受康复训练的58名ASD儿童作为ASD组。按照性别、年龄1∶1匹配的原则,在黑龙江省抽取58名正常发育儿童作为对照组。采集两组儿童空腹静脉血,采用液相色谱-质谱联用技术(LC-MS/MS)和实时荧光定量PCR(RT-qPCR)检测其外周血中内源性大麻素花生四烯酸乙醇胺(AEA)、花生四烯酸甘油(2-AG)、十六酰胺乙醇(PEA)、油酰乙醇胺(OEA)及其代谢酶花生四烯酸磷脂酰乙醇胺特异性磷脂酶D(NAPE-PLD)、酰胺水解酶(FAAH)、单酰基甘油脂酶(MAGL)和二酰基甘油脂酶(DAGL)的mRNA表达水平,采用Pearson相关分析eCB与ASD儿童症状严重程度之间的相关性。结果ASD儿童的AEA、OEA和PEA的水平[(10.10±2.60)nmol/L,(24.30±5.60)nmol/L,(15.92±2.28)nmol/L]均低于对照组儿童[(13.46±3.04)nmol/L,(27.85±6.89)nmol/L,(17.87±2.67)nmol/L,t=-6.612,-3.089,-4.579,均P<0.01];ASD儿童FAAH和DAGL mRNA的表达水平显著高于对照组,且差异有统计学意义(t=2.423,3.840,P<0.05),而NAPE-PLD和MAGL mRNA水平在两组间差异无统计学意义(t=0.024,0.885,均P>0.05);ASD组PEA水平与儿童孤独症行为量表(ABC)总分呈负相关(r=-0.288,P<0.05)。结论ASD儿童体内的eCB及其代谢酶可能存在代谢异常,且eCB水平与ASD的严重程度存在关联性。     

Solid and liquid state characterization of tetrahydrocurcumin using XRPD,FT-IR,DSC, TGA,LC-MS,GC-MS,and NMR and its biological activities

Tetrahydrocurcumin (THC) is one of the major metabolites of curcumin (CUR), an ancient bioactive natural polyphenolic compound. This research article describes both the solid and liquid state characterization of THC using advanced spectroscopic and thermo-analytical techniques. Anti-inflammatory, anti-oxidant, and neuroprotective activities of THC were investigated using in vitro cell lines. Liquid chromatography-mass spectrometry analysis revealed that our sample comprised 95.15% THC, 0.51% tetrahydrodemethoxycurcumin (THDC), 3.40% hexahydrocurcumin, and 0.94% octahydrocurcumin. Gas chromatography-mass spectrometry analysis indicated the presence of 96.68% THC and 3.32% THDC. THC in solution existed as keto-enol tautomers in three different forms at different retention time, but the enol form was found to be dominant, which was also supported by nuclear magnetic resonance analysis. THC was thermally stable up to 335.55 °C. THC exhibited more suppression of cytokines (TNF-α, IL-1β, and MIP-1α) than CUR in a concentration-dependent manner in mouse splenocytes, while NK-cell and phagocytosis activity was increased in macrophages. THC showed a significant reduction of free radicals (LPO) along with improved antioxidant enzymes (SOD and catalase) and increased free radical scavenging activity against ABTS⁺ radicals in HepG2 cells. THC displayed higher protection capability than CUR from oxidative stress and neuronal damage by improving cell viability against H₂O₂ induced HepG2 cells and MPP⁺ induced SH-SY5Y cells, respectively, in a concentration-dependent manner. Thus, a variation of the biological activities of THC might rely on its keto-enol form and the presence of other THC analogs as impurities. The present study could be advantageous for further research on THC for better understanding its physicochemical properties and biological variation.     

抗病毒口服液治疗小儿手足口病肺脾湿热证的随机对照、多中心临床研究

目的 评价抗病毒口服液治疗普通型小儿手足口病肺脾湿热证的有效性及安全性。方法 采用随机、双盲、安慰剂平行对照、多中心临床试验方法,计划纳入288例患儿,按1：1的比例随机分为试验组和对照组。试验组服用抗病毒口服液,对照组服用安慰剂,剂量均为1~2岁5 mL/次、3~6岁10 mL/次,3次/d,疗程5 d。以完全退热时间为主要有效性指标。结果 实际入组287例,其中试验组144例、对照组143例。试验组完全退热中位时间为24 h （PPS数据集,下同）,对照组为48 h,两组比较差异有显著性（P<0.05）;试验组皮疹/疱疹开始消退中位时间为24 h、对照组为40 h,试验组皮疹/疱疹完全消退中位时间为96 h、对照组为112 h,试验组中医证候疗效总愈显率为92.62%、对照组为72.32%,两组比较,差异均有统计学意义（P<0.05）。试验组与对照组不良事件发生率分别为4.35%和2.99%,组间比较,差异无统计学意义。结论 抗病毒口服液治疗小儿手足口病普通型肺脾湿热证,可以缩短退热时间、皮疹/疱疹消退时间,促进口腔黏膜疱疹/溃疡愈合,改善中医证候,临床使用有效、安全。     

芩香清解口服液联合利巴韦林治疗儿童上呼吸道感染的临床研究

目的探讨芩香清解口服液联合利巴韦林注射液治疗儿童上呼吸道感染的临床疗效。方法选取2017年7月—2018年9月新乡医学院第一附属医院收治的上呼吸道感染患儿114例作为研究对象,将患儿根据随机数字表法分为对照组和治疗组,每组各57例。对照组静脉滴注利巴韦林注射液,10mg/kg加入到100m L葡萄糖注射液中充分稀释,1次/d。治疗组在对照组的基础上口服芩香清解口服液,10 mL/次,3次/d。两组患儿均治疗3 d。观察两组患儿的临床疗效,同时比较两组治疗前后的临床症状改善时间和炎症因子水平。结果治疗后,治疗组的总有效率为92.98%,显著高于对照组的78.95%,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组的退热时间、止咳时间、咽痛消失时间、止涕时间均显著短于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组超敏C反应蛋白(hs-CRP)、肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-4(IL-4)水平均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组炎症因子水平明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论芩香清解口服液联合利巴韦林注射液能提高儿童上呼吸道感染的疗效,降低血清炎症因子水平,具有一定的临床推广应用价值。     

金复康口服液联合培美曲塞治疗非小细胞肺癌的临床研究

目的研究金复康口服液联合注射用培美曲塞二钠治疗非小细胞肺癌的临床疗效。方法选取2016年1月—2018年1月南京市胸科医院诊治的120例非小细胞肺癌患者作为研究对象,采用随机对照表法将患者分为对照组和治疗组,每组各60例。对照组静脉滴注注射用培美曲塞二钠500 mg/m~2,静脉输注10 min以上;治疗组患者在对照组治疗的基础上口服金复康口服液,30 mL/次,3次/d。21 d为1个疗程,两组均持续治疗2个疗程。观察两组患者的临床疗效,同时比较两组治疗前后的生活质量(QOL)评分、KPS评分、无进展生存期(PFS)、总生存期(OS)和免疫功能指标水平。结果治疗后,对照组和治疗组的客观缓解率和疾病控制率比较差异无统计学意义。治疗后,两组患者QOL和KPS评分均显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组QOL评分和KPS评分显著高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组患者PFS和OS显著长于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者CD3+、CD4+、NK和CD4+/CD8+水平显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组免疫功能指标水平显著高于对照组,两组比较差异具有统计学意义(P0.05)。结论金复康口服液联合注射用培美曲塞二钠治疗非小细胞肺癌具有较好的临床疗效,能够改善患者生活质量,提高免疫功能,且安全性较高,具有一定临床推广应用价值。     

清脑复神液联合尼莫地平治疗血管性认知障碍的临床研究

目的研究清脑复神液联合尼莫地平片治疗血管性认知障碍的临床疗效。方法选取2015年12月—2018年12月绵阳市中心医院收治的115例血管性认知障碍患者为研究对象,将所有患者随机分为对照组(57例)和治疗组(58例)。对照组患者口服尼莫地平,2片/次,4次/d;治疗组在对照组基础上口服清脑复神液,10 mL/次,2次/d。两组患者持续治疗8周。观察两组的临床疗效,比较两组的蒙特利尔认知评估量表(MoCA)评分、简易精神智能量表(MMSE)评分、血清因子水平。结果治疗后,对照组和治疗组的总有效率分别为85.96%、93.10%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者MoCA评分和MMSE评分均显著升高,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组患者MoCA评分和MMSE评分明显高于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患者神经元特异性烯醇化酶(NSE)和血栓素B2(TXB2)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组患者血清因子水平明显低于对照组,两组比较差异有统计学意义(P0.05)。结论清脑复神液联合尼莫地平片治疗血管性认知障碍具有较好的治疗效果,能改善患者认知功能,降低NSE和TXB2水平,具有一定的临床推广应用价值。     

康复新液治疗口腔正畸慢性牙龈炎的临床疗效

目的研究康复新液在口腔正畸慢性牙龈炎中的应用价值。方法利用奇偶数字分组法对2017年9月-2019年8月本院接诊的口腔正畸后慢性牙龈炎病患76例进行分组(n=38)。对照组实行口腔洁治术治疗,实验组在对照组的基础之上加用康复新液。对比菌斑指数与牙龈疼痛程度等指标。结果实验组总有效率97.37%,比对照组81.58%高,P<0.05。实验组治疗后牙龈疼痛程度(2.86±0.82)分、龈沟出血指数(1.93±0.58)分、菌斑指数(1.09±0.31)分,比对照组(4.09±1.01)分、(2.74±0.91)分、(1.64±0.45)分低,P<0.05。实验组牙龈肿胀程度比对照组轻,P<0.05。结论于口腔正畸后慢性牙龈炎常规口腔洁治术治疗的同时,利用康复新液对患者进行佐治,可显著提升疗效,促进牙龈疼痛程度缓解,改善龈沟出血指数与菌斑指数,建议推广。