金复康口服液对吉非替尼耐药人肺腺癌PC9/R的增敏作用和机制研究

目的 研究金复康口服液对人肺腺癌PC9细胞及耐药PC9/R细胞的吉非替尼增敏作用及机制。方法 金复康口服液20 mg/mL联合不同浓度的吉非替尼（40、20、10、5、2 μmol/L）作用于PC9/R细胞,CCK-8法检测细胞增殖;培养PC9、PC9/R细胞,分为对照组、金复康口服液组、吉非替尼组、联合用药组,流式细胞术检测PC9、PC9/R细胞周期和凋亡。在BALB/c裸鼠右前肢腋窝皮下接种PC9/R细胞建立裸鼠移植瘤模型,观察金复康口服液联合吉非替尼的体内抑瘤作用;对AKT、p-AKT、PTEN、PDCD4蛋白表达的影响和对miRNA-21表达的影响。结果 与吉非替尼（2、5、10、20 μmol/L）组比较,吉非替尼（2、5、10、20 μmol/L）+金复康口服液（20 mg/mL）组的PC9/R细胞抑制率显著增加（P<0.01）;与吉非替尼组比较,联合用药可以通过显著增加早期凋亡细胞比例诱导PC9及PC9/R细胞凋亡,并使PC9、PC9/R细胞停滞在DNA合成前期,从而抑制细胞增殖,差异均具有统计学意义。体内实验表明,与吉非替尼组比较,联合用药显著抑制裸鼠PC9/R移植瘤的生长（P<0.05）,且能显著降低裸鼠PC9/R组织p-AKT表达（P<0.05）,增强PTEN、PDCD4的表达（P<0.05）,联合用药组裸鼠PC9/R瘤组织miRNA-21的表达显著降低（P<0.05）。结论 金复康口服液能提高人肺腺癌PC9/R细胞对吉非替尼的敏感性,其作用的可能机制为通过降低miRNA-21的表达从而增强PTEN、PDCD4的表达以抑制AKT通路活性。     

鼻渊舒口服液与西药治疗慢性鼻窦炎的临床疗效及安全性对比分析

目的研究并对比鼻渊舒口服液与西药治疗慢性鼻窦炎的临床疗效及安全性。方法 2013年1~12月该院门诊就诊的慢性鼻窦炎患者共186例。以数字法随机分成观察组(93例)和对照组(93例)。观察组患者使用鼻渊舒口服液进行治疗;对照组患者则使用西药进行治疗。对两组患者进行为期40d的治疗后,通过患者的治疗效果、用药后并发症以及治疗后的复发情况来比较两组患者的治疗情况。结果通过40d的治疗后发现观察组和对照组的临床疗效都比较好,两组的治疗效果差异无统计学意义(P0.05)。在治疗中因为用药导致全身多个系统出现并发症,观察组的总并发症发生率为4.3%,对照组30.11%,两组恶心呕吐、头晕目眩、全身乏力及总并发症发生率差异均有统计学意义(均P0.05)。在治疗结束后两组患者均出现不同程度上的病情复发,观察组有8例(8.60%)患者出现复发,而对照组中则有32例(34.41%)患者出现复发,两组复发率差异有统计学意义(P0.05)。结论使用鼻渊舒口服液对慢性鼻窦炎进行治疗后发现治疗结果良好,并发症少,值得在临床上广泛推广。     

相变型链霉亲和素化PLGA纳米粒的制备

目的 制备一种相变型链霉亲和素化的聚乳酸-羟基乙酸共聚物(PLGA)纳米粒(PLGA-SA/PFP),研究体外热致相变、声致相变增强超声显影的效果.方法 采用单乳化法及碳二亚胺法制备PLGA-SA/PFP,显微镜加热板法进行热致相变,低强度聚焦超声(LIFU)进行声致相变.结果 PLGA-SA/PFP的平均粒径为(346.2±74.49) nm,链霉亲和素结合量为2 208个分子/纳米粒.43.7℃时纳米粒发生相变,LIFU作用后可观察到超声显影增强.结论 成功制备了PLGA-SA/PFP,可用于预定位靶向实验.     

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.     

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。