18F-FDG PET-CT在肺癌诊断中的应用

肺癌是目前最常见的肿瘤相关性死亡原因之一.每年全球新增病例约400万.同时,肺癌也是我国肿瘤发病及死亡的首要原因[1].并且,肺癌的预后与临床分期密切相关,0～Ⅳ期肺癌病人5年生存率从90%降到5%以下.     

非小细胞肺癌的治疗和研究

据有关资料显示,作为恶性肿瘤之一的肺癌,全球每年新增病例达50万例。目前,我国的肺癌发病率由20世纪70年代肿瘤发病率的第四位,跃居为恶性肿瘤发病牢的第一位;肺癌的死亡率,男性为6.82/10万,女性为3.20/10万;肺癌死亡率在恶性肿瘤中所占百分比,男性为8.51%,女性为5.90%。     

替雷利珠单抗致肾上腺皮质功能减退症1例

<正>据2021年世界卫生组织国际癌症研究机构发布的最新流行病学数据^[1]显示,肺癌每年约有220万新发病例和180万例死亡病例,是全球癌症死亡的主要原因之一。其中,非小细胞肺癌(NSCLC)约占肺癌发病率的80%,晚期患者预后不佳^[2]。免疫检查点抑制剂(immune checkpoint inhibitor, ICI)单用或与其他治疗方法联用是晚期NSCLC的治疗方案之一^[3]。     

肺癌贫血的治疗进展

肺癌每年新发病例接近120万,是癌症死亡的首位原因,近半世纪以来,肺癌的发病率和死亡率呈迅速上升趋势。2006年美国约有174000例新发病例,有162000例死于肺癌[1]。贫血是肺癌患者常见的临床症状之一,它影响着患者的健康、生活质量,甚至生存时间。有研究表明,70%～75%的肺癌患者以及50%～75%正在接受单一或综合治疗的非骨髓来源的恶性肿瘤患者可能发生贫血[2]。贫血导致病人乏力、嗜睡、抑郁、     

优质护理服务模式对晚期胃癌患者疼痛的影响效果

近年来,胃癌的患病率呈现上升趋势,病死率仅次于肺癌、肝癌,全球每年新发病例接近100万,41%发生在中国;全球每年因胃癌死亡80万,中国占35%[1,2]。目前,手术治疗仍是胃癌患者重要临床措施[3]。但是,由于其发病隐匿,患者确诊时往往已处于癌症中晚期,则可考虑手术联合应用化疗可显著提     

药品不良反应监测浅析

据世界卫生组织统计,世界每年死亡病例中约有5%系药物不良反应所致.据测算我国因药物不良反应每年死亡人数约达20万左右.现将有关药物不良反应监测内容浅析如下.     

肿瘤靶向药物应用前景广阔——中国工程院院士甄永苏谈肿瘤靶向药物的研发现状与未来

据统计,2020年全世界癌症发病率将比现在增加50%,全球每年新增癌症患者人数将达到1500万人。我国近20年来癌症发病率上升了69%,死亡率上升了29%,每年癌症新发病例为220万,因癌症死亡人数     

孕妇感染甲型H3N2流感死亡病例的病因学分析

<正>流行性感冒是由流感病毒引起的一种急性呼吸道传染病,每年全球的罹患率约为成人5%～10%,儿童20%～30%,导致300万～500万例的重症病例和25万～50万例的死亡。孕期妇女由于特殊的生理及免疫系统变化,感染流感病毒后容易发展为重症并导致死亡~([1])。现对本市1例孕晚期感染流感死亡病例进行流行病学调查分析,报告如下。1对象与方法该死亡病例为长治医学院附属和平医院2017年12月     

NSCLC的分期及内科治疗新进展

2007年肺癌发病率最新统计结果：全世界每年新发病例〉125万．死亡〉115万。中国发病率〉55万。在所有癌性死亡中，肺癌占28．2％，男女均列第1位。其中75％-80％为非小细胞肺癌（NSCLC），NSCLC中仅有15％-20％的早期（Ⅰ、Ⅱ期）患者可以经手术治疗．其中80％的晚期（Ⅲb、Ⅳ）患者均为全身化疗的适应证，需要有效的化疗药物进行治疗，因此寻求高效、低毒的化疗方案是提高肺癌生存率、改善患者生存质量的关键。本文对NSCLC的分期及内科治疗做一综述。     

吉西他滨+顺铂联合小牛脾提取物注射液治疗非小细胞肺癌30例临床疗效观察

<正>肺癌是全球最常见的癌症之一,据统计每年有120万新增病例,其中非小细胞肺癌约占80%。肺癌更是中国第一致死癌症,每年有60万患者死于肺癌。由于早期具有隐蔽性,大多数非小细胞肺癌患者发现时已是局部晚期或发生转移,超过半数的肺癌患者会错过手术机会。即使能手     

Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

Aim： Prenatal nicotine exposure （PNE） alters the hypothalamic-pituitary-adrenocortical （HPA） axis-associated neuroendocrine metabolic programming in intrauterine growth retardation offspring rats. In this study we aimed to clarify the susceptibility to metabolic diseases of PNE offspring rats fed a high-fat diet. Methods： Maternal Wistar rats were injected with nicotine （1.0 mg/kg, sc） twice per day from gestational day 11 until full-term delivery, and all pups were fed a high-fat diet after weaning and exposed to unpredictable chronic stress （UCS） during postnatal weeks 18-20. Blood samples were collected before and after chronic stress, and serum ACTH, corticosterone, glucose, insulin, total cholesterol, triglyceride and free fatty acids levels were measured. The hypothalamus, pituitary gland and liver were dissected for histological studies. Results： UCS significantly increased the serum ACTH, corticosterone and insulin levels as well as the insulin resistant index without changing the serum glucose, total cholesterol, triglyceride and free fatty acids levels in adult offspring rats without PNE. The body weight of PNE offspring rats presented a typical ＂catch-up＂ growth pattern. PNE not only aggravated the UCS-induced changes in the HPA axis programmed alteration （caused further increases in the serum ACTH and corticosterone levels）, but also significantly changed the glucose and lipid metabolism after UCS （caused further increases in the serum glucose level and insulin resistant index, and decrease in the serum free fatty acids）. The effects of PNE on the above indexes after UCS showed gender differences. Pathological studies revealed that PNE led to plenty of lipid droplets in multiple organs. Conclusion： PNE enhances not only the HPA axis, but also the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet after UCS in a gender-specific manner and enhances the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet.     

Hsp90 inhibitor BILBO21 enhances triptolide-induced apoptosis of human T-cell acute lymphoblastic leukemia cells in vitro mainly by disrupting p53- MDM2 balance

Aim： To investigate the effects of BILBO21, an inhibitor of heat shock protein 90 （Hsp90） alone or in combination with triptolide （TPL） on T-cell acute lymphoblastic leukemia （T-ALL） and the mechanisms of action. Methods： Human T-ALL cells line Molt-4 was examined. The cell viability was measured using M]-I- assay. Apoptotic cells were studied with Hoechst 33258 staining. Cell apoptosis and cell cycle were analyzed using flow cytometry with Annexin V/PI staining and PI staining, respectively. The levels of multiple proteins, including Akt, p65, CDK4/6, p18, Bcl-2 family proteins, MDM2, and p53, were examined with Western blotting. The level of MDM2 mRNA was determined using RT-PCR. Results： Treatment of Molt-4 cells with BILBO21 （50-800 nmol/L） inhibited the cell growth in a dose-dependent manner （the IC~ovalue was 384.6 and 301.8 nmol/L, respectively, at 48 and 72 h）. BILBO21 dose-dependently induced Go/G1 phase arrest, followed by apoptosis of Molt-4 cells. Furthermore, BILBO21 increased the expression of p18, decreased the expression of CDK4/6, and activated the caspase pathway in Molt-4 cells. Moreover, BILBO21 （50-400 nmol/L） dose-dependently decreased the phospho-MDM2 and total MDM2 protein levels, but slightly increased the phospho-p53 and total p53 protein levels, whereas TPL （5-40 nmol/L） dose- dependently enhanced p53 activation without affecting MDM2 levels. Co-treatment with BILBO21 and TPL showed synergic inhibition on Molt-4 cell growth. The co-treatment disrupted p53-MDM2 balance, thus markedly enhanced p53 activation. In addition, the co-treatment increased the expression of Bak and Bim, followed by increased activation of caspase-9. Conclusion： The combination of BILBO21 and TPL may provide a novel strategy for treating T-ALL by overcoming multiple mechanisms of apoptosis resistance.     

Stereoselective binding of doxazosin enantiomers to plasma proteins from rats,dogs and humans in vitro

Aim： （＋）Doxazosin is a long-lasting inhibitor of a1-adrenoceptors that is widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms. In this study we investigated the stereoselective binding of doxazosin enantiomers to the plasma proteins of rats, dogs and humans in vitro. Methods： Human, dog and rat plasma were prepared. Equilibrium dialysis was used to determine the plasma protein binding of each enantiomer in vitro. Chiral HPLC with fluorescence detection was used to measure the drug concentrations on each side of the dialysis membrane bag. Results： Both the enantiomers were highly bound to the plasma proteins of rats, dogs and humans [（-）doxazosin： 89.4%-94.3%; （＋）doxazosin： 90.9%-95.4%]. （＋）Doxazosin exhibited significantly higher protein binding capacities than （-）doxazosin in all the three species, and the difference in the bound concentration （Cb） between the two enantiomers was enhanced as their concentrations were increased. Although the percentage of the plasma protein binding in the dog plasma was significantly lower than that in the human plasma at 400 and 800 ng/mL, the corrected percentage of plasma protein binding was dog〉human〉rat. Conclusion： （-）Doxazosin and （＋）doxazosin show stereoselective plasma protein binding with a significant species difference among rats, dogs and humans.     

美国与欧洲上市后药品安全风险管理进展概述

近10年来,美国食品药品管理局（FDA）、欧洲药品管理局（EMA）及其他相关单位,对上市后药品安全性监测日益重视,在这一领域取得了显著进展,并且制定了一系列新规定。     

Sodium hydrosulfide alleviates lung inflammation and cell apoptosis following resuscitated hemorrhagic shock in rats

Aim： To investigate the protective effects of hydrogen sulfide （H2S） against inflammation, oxidative stress and apoptosis in a rat model of resuscitated hemorrhagic shock. Methods： Hemorrhagic shock was induced in adult male SD rats by drawing blood from the femoral artery for 10 min. The mean arterial pressure was maintained at 35-40 mmHg for 1.5 h. After resuscitation the animals were observed for 200 min, and then killed. The lungs were harvested and bronchoalveolar lavage fluid was prepared. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. NariS （28 pmol/kg, ip） was injected before the resuscitation. Results： Resuscitated hemorrhagic shock induced lung inflammatory responses and significantly increased the levels of inflammatory cytokines IL-6, TNF-a, and HMGB1 in bronchoalveolar lavage fluid. Furthermore, resuscitated hemorrhagic shock caused marked oxidative stress in lung tissue as shown by significant increases in the production of reactive oxygen species H202 and OH, the translocation of Nrf2, an important regulator of antioxidant expression, into nucleus, and the decrease of thioredoxin I expression. Moreover, resuscitated hemorrhagic shock markedly increased the expression of death receptor Fas and Fas-ligand and the number apoptotic cells in lung tissue, as well as the expression of pro-apoptotic proteins FADD, active-caspase 3, active-caspase 8, Bax, and decreased the expression of Bcl-2. Injection with NariS significantly attenuated these pathophysiological abnormalities induced by the resuscitated hemorrhagic shock. Conclusion： NariS administration protects rat lungs against inflammatory responses induced by resuscitated hemorrhagic shock via suppressing oxidative stress and the Fas/FasL apoptotic signaling pathway.     

人参北芪片的质量控制研究

目的建立人参北芪片的质量标准,控制制剂的质量。方法采用薄层色谱法对制剂中组成药味人参进行鉴别,采用HPLC-蒸发光散射检测法测定制剂中的黄芪甲苷,并进行方法学考察。结果人参的薄层鉴别中,斑点清晰,阴性无干扰。黄芪甲苷在0.9976～14.9640μg与峰面积呈良好的线性关系,平均回收率为98.06%,RSD为1.60%。结论建立的薄层色谱和高效液相色谱定性、定量方法可以用来控制人参北芪片的质量,方法简便可行。     

Molecular modeling,quantum polarized ligand docking and structure-based 3D-QSAR analysis of the imidazole series as dual AT~ and ETA receptor antagonists

Aim： Both endothelin ETA receptor antagonists and angiotensin AT1 receptor antagonists lower blood pressure in hypertensive patients. A dual AT1 and ETA receptor antagonist may be more efficacious antihypertensive drug. In this study we identified the mode and mechanism of binding of imidazole series of compounds as dual AT1 and ETA receptor antagonists. Methods： Molecular modeling approach combining quantum-polarized ligand docking （QPLD）, MM/GBSA free-energy calculation and 3D-QSAR analysis was used to evaluate 24 compounds as dual AT1 and ETA receptor antagonists and to reveal their binding modes and structural basis of the inhibitory activity. Pharmacophore-based virtual screening and docking studies were performed to identify more potent dual antagonists. Results： 3D-QSAR models of the imidazole compounds were developed from the conformer generated by QPLD, and the resulting models showed a good correlation between the predicted and experimental activity. The visualization of the 3D-QSAR model in the context of the compounds under study revealed the details of the structure-activity relationship： substitution of methoxymethyl and cyclooctanone might increase the activity against AT~ receptor, while substitution of cyclohexone and trimethylpyrrolidinone was important for the activity against ETA receptor; addition of a trimethylpyrrolidinone to compound 9 significantly reduced its activity against AT~ receptor but significantly increased its activity against ETA receptor, which was likely due to the larger size and higher intensities of the H-bond donor and acceptor regions in the active site of ETA receptor. Pharmacophore-based virtual screening followed by subsequent Glide SP, XP, QPLD and MM/GBSA calculation identified 5 potential lead compounds that might act as dual AT1 and ETA receptor antagonists. Conclusion： This study may provide some insights into the development of novel potent dual ETA and AT1 receptor antagonists. As a result, five compounds are found to be the best dual antagonists against AT1R and ETA receptors.     

树突状细胞的肿瘤个体化治疗

肿瘤免疫治疗这一概念是基于机体的免疫系统在对抗肿瘤时的调节与反应。有效的免疫治疗的最主要的优点在于相对较少的副作用,针对肿瘤细胞的靶向特异性,并且能产生对抗肿瘤特异性抗原的长期记忆[1]。