PF方案同步放化疗治疗中晚期宫颈癌的疗效及毒性反应研究

目的：探究PF 方案同步放化疗治疗中晚期宫颈癌患者的疗效和毒性反应。方法：回顾性分析我院在2014 年6 月～2015 年6 月期间收治的ⅡB～Ⅲ期宫颈癌患者,共152 例,根据治疗方法将其分为单纯放疗组和同步放化疗组,比较两组患者治疗的疗效 和毒性反应。结果：单纯放疗组和同步放化疗组近期疗效总有效率无显著差异,差异不具有统计学意义(P>0.05),但分别对ⅡB 和 Ⅲ期患者进行分析,Ⅲ期患者同步放疗组总有效率显著高于单纯放疗组,差异具有统计学意义(P<0.05);同步放化疗组患者治疗 后骨髓抑制白细胞下降和消化道反应发生率显著高于单纯放疗组,差异具有统计学意义(P<0.05),两组患者皮肤反应的发生情况 比较无显著差异(P>0.05)。结论：PF方案同步放化疗治疗Ⅲ期宫颈癌的临床疗效显著优于单纯放疗治疗,可有效提高近期总有效 率,毒性反应虽较单纯放疗组有所增加,但经临床支持治疗患者均可耐受。     

应用药物动力学评价按(一级并行)米氏过程消除药物的给药方案:静脉点滴

本文讨论符合（一级并行）米氏消除药物的多剂量静脉点滴给药的给药方案评价方法并给出了应用例子。     

Insights of synthetic analogues of anti-leprosy agents

Today, the emergence of the phenomenon of drug or multidrug-resistance for community-associated diseases represents a major concern in the world. In these contexts, the chronic infectious disease, leprosy, grounded by a slow-growing bacterium called Mycobacterium leprae or Mycobacterium lepromatosis is a leading cause of severe disfiguring skin sores and nerve damage in the arms, legs, and skin areas around the body. Even, over 200,000 new leprosy cases are being accounted every year along with the relapsed leprosy cases. Nonetheless, this has been considered a curable disease with a higher dose of multidrug therapy (MDT) for a long period of time. The prolonged action of a high dose of combination drugs administration may cause an adverse reaction that can significantly affect patient compliance, particularly the outbreak of multidrug-resistance in the infected person. To overcome these shortfalls or prevent the resistance-associated problems, researchers are diligently involved in the structural modifications of the clinically used anti-leprosy drugs or the allied compounds for the structure-antimycobacterial activity relationship study. This review article described the detailed synthesis and biological assays of different anti-leprosy compounds reported by several research groups.     

Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi® and Epclusa®

Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa^®, an STR with 98% cure-rates for genotype 1–6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi^®, which affords 97% cure-rates for genotype 1–6 HCV patients who have previously failed another treatment regimen.     

A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients

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Highlights

• •Increased proteome coverage with Orbitrap Exploris 480 MS and FAIMS using single compensation voltages and short LC gradients.
• •Towards single-cell proteomics with high-sensitivity analysis of 5 ng HeLa with more than 1,000 proteins identified in 5 minutes using FAIMS and DIA.
• •Deep proteome profiling across twelve rat organs tissues by label-free quantitation using DIA compared to TMT-multiplexing and turboTMT acquisition using phi-SDM.
• •Rapid and sensitive phosphoproteomics with automated enrichment using Ti-IMAC magnetic beads and direct DIA analysis.

     

Expression of a novel P275L variant of NADH:cytochrome b5 reductase gives functional insight into the conserved motif important for pyridine nucleotide binding

The clinical disorder of recessive congenital methemoglobinemia (RCM, OMIN 250800) is associated with mutations in NADH:cytochrome b5 reductase (cb5r) and manifests as cyanosis from birth. Screening a cyanotic infant indicated elevated methemoglobin levels and decreased cb5r activity suggesting RCM. Sequencing the DIA1 gene encoding cb5r revealed a novel mutation, C27161T (NCBI accession number: NT_011520), resulting in replacement of proline at amino acid 275 with leucine (P275L). To understand how this mutation would affect cb5r's function, the P275L variant was expressed in a heterologous expression system and spectroscopic, thermodynamic, and thermostability studies were performed. The leucine substitution at residue 275 was found to significantly decrease the affinity towards the physiological reducing substrate, NADH, without affecting the activity of the P275L variant. From the rat model, residue 275 is predicted to be part of a conserved "CGPPPM" motif important for the binding and correct positioning of the NADH reducing substrate. Thus P275 influences the interaction with NADH which was confirmed by the change in affinity towards the physiological reducing substrate.     

The Goeckerman Regimen for the Treatment of Moderate to Severe Psoriasis

Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting approximately 2-3% of the population. The Goeckerman regimen consists of exposure to ultraviolet B (UVB) light and application of crude coal tar (CCT). Goeckerman therapy is extremely effective and relatively safe for the treatment of psoriasis and for improving a patient''s quality of life. In the following article, we present our protocol for the Goeckerman therapy that is utilized specifically at the University of California, San Francisco. This protocol details the preparation of supplies, administration of phototherapy and application of topical tar. This protocol also describes how to assess the patient daily, monitor for adverse effects (including pruritus and burning), and adjust the treatment based on the patient''s response. Though it is one of the oldest therapies available for psoriasis, there is an absence of any published videos demonstrating the process in detail. The video is beneficial for healthcare providers who want to administer the therapy, for trainees who want to learn more about the process, and for prospective patients who want to undergo treatment for their cutaneous disease.     

The daily rhythms of melatonin and free fatty acids in goats under varying photoperiods and constant darkness

The purpose of the study was to explore parallel and divergent features of the daily rhythms of melatonin and plasma free fatty acids (FFA) in goats exposed to different lighting conditions. From these features, we attempted to analyze whether the endogenous melatonin rhythm plays any role in the maintenance of the FFA rhythm. Seven Finnish landrace goats were kept under artificial lighting that simulated the annual changes of photoperiod at 60°N (longest photoperiod, 18 h; shortest, 6 h). The ambient temperature and feeding regimen were kept constant. Blood samples were collected 6 times a year at 2 h intervals for 2 d, first in the prevailing light‐dark (LD) conditions and then after 3 d in constant darkness (DD). In LD conditions, the melatonin levels always increased immediately after lights‐off and declined around lights‐on, except in winter (18 h darkness), when the low daytime levels were restored clearly before lights‐on. The FFA levels also displayed a consistent rhythmicity, with low levels at night and a transient peak around lights‐on. In DD conditions, the melatonin profiles were very similar to those found in the habitual LD conditions, but the rhythm tended to advance. The FFA rhythm persisted also in DD, and the morning peak tended to advance. There was an overall parallelism between the two rhythms, with one significant exception. In winter in LD conditions, the morning rise in FFA levels coincided with lights‐on and not with the declining phase of melatonin, whereas in DD conditions, the FFA peak advanced several hours and coincided with the declining phase of melatonin. From this finding and comparisons of the calculated rhythm characteristics, i.e., phase‐shifts, phase differences, and correlations, we conclude that the daily rhythm of FFA levels is most probably generated by an endogenous oscillator, primarily adjusted by dawn, whereas the melatonin rhythm in this species is regulated by an oscillator primarily adjusted by dusk. The results did not exclude a modulatory effect of melatonin on the daily FFA profiles, but melatonin secretion, alone, does not explain the patterns sufficiently.     

Laboratory rearing of wild Arctic cod Boreogadus saida from egg to adulthood

The techniques and protocols used to successfully capture, transport and breed Arctic cod Boreogadus saida, as well as to rear their larvae through to adulthood are summarized. Breeding B. saida will increase the opportunity to study this fish species, which is a critical part of the Arctic food web.     

艾迪注射液联合XELOX方案对晚期结直肠癌患者肿瘤标志物、血管生成和外周血Th17/Treg平衡的影响

摘要 目的：观察艾迪注射液联合XELOX方案（卡培他滨+奥沙利铂）对晚期结直肠癌患者肿瘤标志物、血管生成和外周血辅助性T细胞17（Th17）/调节性T细胞（Treg）平衡的影响。方法：选择我院2018年2月~2019年8月期间收治的98例经内镜活检证实的晚期结直肠癌患者,根据随机数字表法分为对照组（XELOX方案化疗,49例）和研究组（艾迪注射液联合XELOX化疗方案治疗,49例）。观察两组患者近、远期疗效,对比两组治疗前后的肿瘤标志物、血管生成和Th17/Treg平衡相关指标水平,记录两组用药安全性。结果：与对照组相比,研究组的客观缓解率、疾病控制率明显更高（P<0.05）;研究组的总生存率、无进展生存率高于对照组,但两组间差异无统计学意义（P>0.05）。治疗后,两组癌胚抗原（CEA）、糖链抗原125（CA125）、糖链抗原242（CA242）水平均下降,且研究组低于对照组同期（P<0.05）。治疗后,两组血管内皮生长因子（VEGF）、肿瘤微血管密度（MVD）水平均下降,且研究组低于对照组同期（P<0.05）。治疗后,两组Th17比例、Th17/Treg比值均升高,Treg比例均下降（P<0.05）;研究组治疗后Th17比例、Th17/Treg比值高于对照组同期,Treg比例低于对照组同期（P<0.05）。两组不良反应总发生率对比未见明显差异（P>0.05）。结论：艾迪注射液联合XELOX方案治疗晚期结直肠癌的疗效确切,可能与改善Th17/Treg平衡、抑制血管生成有关。