DEB-TACE联合卡瑞利珠单抗治疗中晚期肝癌的临床疗效及对肿瘤标志物和T淋巴细胞亚群的影响

摘要 目的：探讨载药微球-肝动脉化疗栓塞术（DEB-TACE）联合卡瑞利珠单抗治疗中晚期肝癌的临床疗效及对肿瘤标志物和T淋巴细胞亚群的影响。方法：采用随机数字表法,将徐州医科大学附属医院于2019年7月-2020年7月期间收治的80例中晚期肝癌患者分为对照组（DEB-TACE治疗,n=40）和研究组（对照组的基础上接受经肝动脉灌注卡瑞利珠单抗治疗,n=40）。对比两组疗效、血清肿瘤标志物、T淋巴细胞亚群指标的变化情况和总生存期（OS）、无进展生存期（PFS）,并观察两组不良反发生情况。结果：研究组的客观缓解率（ORR）、疾病控制率（DCR）均高于对照组（P<0.05）。两组治疗1个月后CD8⁺下降,且研究组低于对照组同期（P<0.05）,CD3⁺、CD4⁺、CD4⁺/CD8⁺升高,且研究组高于对照组同期（P<0.05）。两组治疗1个月后甲胎蛋白（AFP）、异常凝血酶原（PIVKA-II）下降,且研究组低于对照组同期（P<0.05）。研究组的OS（中位OS为13.3个月,2年生存率30.00%）、PFS（中位OS为8.2个月,2年生存率17.50%）,均长于对照组（P<0.05）。两组不良反应发生率对比无差异（P>0.05）。结论：DEB-TACE联合经肝动脉灌注卡瑞利珠单抗治疗中晚期肝癌,可改善免疫功能,降低血清肿瘤标志物水平,安全有效。     

依托咪酯靶控输注联合右美托咪定对胃癌根治术患者应激反应、炎症因子和细胞免疫功能的影响

摘要 目的：观察胃癌根治术患者在依托咪酯靶控输注联合右美托咪定麻醉下,机体细胞免疫功能、炎症因子、应激反应的影响。方法：选取2021年4月~2022年6月期间我院收治的择期行胃癌根治术患者100例,按照信封抽签的形式将患者分为对照组（n=50）和观察组（n=50）,对照组患者麻醉选用依托咪酯注射液靶控输注,观察组则在对照组的基础上结合静脉输注盐酸右美托咪定注射液。观察两组患者不良反应发生情况、血流动力学指标[心率（HR）、收缩压（SBP）、舒张压（DBP）]、应激反应指标[皮质醇（Cor）、肾上腺素（E）、促肾上腺皮质激素（ACTH）]、炎症因子[肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）、超敏C反应蛋白（hs-CRP）]、细胞免疫功能指标。结果：观察组用药时、拔管时SBP、HR、DBP低于对照组（P<0.05）。两组不良反应发生率组间对比无差异（P>0.05）。观察组术后1 d E、IL-6、Cor、TNF-α、ACTH、 hs-CRP、 CD8⁺低于对照组（P<0.05）。观察组术后1 d CD4⁺、CD3⁺、CD4⁺/CD8⁺高于对照组（P<0.05）。结论：胃癌根治术患者使用依托咪酯靶控输注联合右美托咪定麻醉,血流动力学、应激反应可得到有效控制,炎症因子、免疫功能的影响也可大大减轻,利于手术的顺利进行。     

Damage and repair in mammalian cells after exposure to non-ionizing radiations : I. Ultraviolet and visible light irradiation of cells of the rat kangaroo (Potorous tridactylus) and determination of photorepairable damage in vitro

Cornea cells of the rat kangaroo or “potoroo” (Potorous tridactylus) were exposed to far-UV (254 or 302 nm) radiation, with or without subsequent illumination by near-UV or visible light. The DNA of these cells was extracted and tested for the presence of photoproducts binding yeast photoreactivating enzyme (PRE). The criterion for the latter was competitive inhibition of an in vitro photorepair system, consisting of UV-irradiated transforming DNA of Haemophilus influenzae and an extract containing yeast PRE. The effects on repair kinetics of the transforming DNA indicate that in UV-irradiated potoroo cornea cells up to approximately 90% of photorepairable DNA damage can be photorepaired within 15 min. However, the extent of cellular photorepair, assessed by the reduction in competitive inhibition of the in vitro repair system depends appreciably on experimental parameters during photoreactivating treatment. Control experiments with non-UV-irradiated cells indicated that, depending on specific conditions, the photoreactivating treatment itself produces a varying amount of DNA damage, which reacts with the PRE in vitro. To avoid most of this kind of damage, cells are nitrogen-gassed and kept at 5°C during illumination, and the photoreactivating light must not contain wavelengths shorter than 380–400 nm. Our results show that wavelengths >470 nm are still very effective, whereas wavelengths >555 nm are ineffective in photorepairing potoroo DNA. For unknown reasons, one particular strain of potoroo cornea cells lost its potential for photorepair. Treatment of unirradiated potoroo cells, or their extracted DNA, with hydrogen peroxide also results in competitive inhibition of photorepair in vitro, resembling that observed after near-UV illumination. Because of the occurrence of synergistic effects it is not clear whether the damage only interacts with PRE or can actually be photorepaired under appropriate conditions.

The results presented in this paper suggest that the expression of photorepair in mammalian cells, unlike that in prokaryotes, greatly depends on a number of experimental parameters, including the spectral composition of photoreactivating light. Apparently superposition of damage by the photoreactivating treatment itself is the critical factor. This may explain experimental discrepancies existing in different laboratories studying photorepair in UV-irradiated cells of placental mammals.     

MRNA encoding a putative RNA helicase of the DEAD-box gene family is up-regulated in trypomastigotes of Trypanosoma cruzi

Differential display of mRNAs from Trypanosoma cruzi epimastigote and metacyclic trypomastigote stages showed several mRNA species differing in their expression level. The cDNA corresponding to one of these mRNAs was used as a probe in Northern blots and identified a RNA product of 2.6 kb with an expression level eight or more times higher in trypomastigotes than in epimastigotes. This probe was also used to screen a genomic library of T. cruzi CL Brener clone prepared in lambda FIX. A clone of about 15 kb was selected that, after partial sequencing, revealed an open reading frame of 688 amino acids encoding a deduced protein with similarity to RNA helicases of the DEAD-box gene family. The presence of the eight conserved motifs characteristic of the DEAD protein family was observed in the T. cruzi sequence, indicating that it corresponds to a putative RNA helicase gene, which we named HelTc. Southern blot analysis indicated that HelTc is a single-copy gene. Pulsed-field gel electrophoresis separation of chromosomes of several isolates of T. cruzi showed that this gene was localized in one or two chromosomal bands.     

Effect of differently induced plasma norepinephrine increments on norepinephrine sulfate formation

We investigated whether similar increments in venous plasma norepinephrine (NE) concentration caused by exercise and by intravenous NE infusion will elevate plasma norepinephrine sulfate (NES) to similar concentrations. In randomized order venous plasma NE concentration was elevated to similar concentrations by bicycle exercise (BE; 65% VO(2)max) and by intravenous NE infusion at rest (INF; 0.14 microg/min/kg). N = 11 subjects participated in the study. Increments in plasma NE and the area under curve of plasma NE were similar during BE (11.2 +/- 1.3 nM; 411 +/- 23 nM/min; means +/- S.E.) and INF (12.6 +/- 1.9 nM; 429 +/- 27 nM/min). Plasma NES was significantly elevated to similar concentrations with BE (from 5.7 +/- 1.0 to 8.5 +/- 1.3 nM) and with INF (from 5.6 +/- 0.9 to 8.9 +/- 1.0 nM). Plasma NE and NES concentration during control conditions remained unchanged. Heart rate decreased significantly to 43 +/- 1 beats/min with INF and increased significantly to 162 +/- 3 beats/min with BE. Systolic blood pressure increased with both, INF and BE (155 +/- 3 mmHg; 179 +/- 6 mmHg, respectively). Present findings firstly show that intravenously infused NE is sulfoconjugated in humans, indicating that a major part of NE is sulfoconjugated in blood or at sites easily accessible from blood. Secondly, plasma NE may be a useful additional marker for NES release.     

尿激酶颈动脉灌注治疗急性脑梗死疗效观察

目的：研究小剂量尿激酶颈动脉加压灌注治疗急性脑梗死的效果。方法选择８０例急性梗死住院病人按入院顺序随机分为治疗组（颈动脉灌注组）和对照组,各４０例,治疗组入院后即给予尿激酶３０万单位于患侧颈动脉加压灌注,同时给予低分子右旋糖酐５００ｍｌ、脉胳宁２０ｍｌ、有脑水肿者给予甘露醇、细胞活化剂、钙离子拮抗剂同时应用;对照组除尿激酶外用药相同,两组于治疗前及治疗后１５天按临床神经功能缺损程度评分标准作出疗效     

周期性静滴给药的稳态动力学研究

对线性一定模型的药物,周期静滴给药的动力学模型为一分段连续函数,本文对其动态动力学特征进行了研究,得到了稳态浓度的ｃ－ｔ方程以及一次给药和多次给药动力学参数之间的关系。为预测稳态浓度提供了依据,在此基础上对给药方案的拟定进行了讨论。     

Induction of mutation to streptomycin resistance in Micrococcus radiodurans.

No detectable induction of mutation to streptomycin resistance could be used in wild-type Micrococcus radiodurans and its radiation-sensitive and super-resistant mutants by ionizing or UV-radiation. N-methyl-N'-nito-N-nitrosoguanidine (NTG) was mutagenically active. The results suggest that repair of radiation-damaged DNA in Micrococcus radiodurans is mutation-proof.     

Estudio observacional de infusión subcutánea continua de insulina a lo largo de 7 años en el tratamiento de la diabetes mellitus tipo 1

This work reports the experience with use of continuous subcutaneous insulin infusion (CSII) in 112 type 1 diabetic patients followed up for 7 years and previously treated with multiple daily insulin injections (MDII).Material and methodsA retrospective, observational study in 112 patients with diabetes mellitus treated with CSII from 2005 to 2012, previously treated with MDII and receiving individualized diabetic education with a specific protocol. Variables analyzed included: prevalence of the different indications of pump treatment; mean annual HbA1c and fructosamine values before and after CSII treatment; and hypoglycemia frequency and symptoms.ResultsThe most common reason for pump treatment was brittle diabetes (74.1%), followed by frequent or severe hypoglycemia or hypoglycemia unawareness (44.6%). Other indications were irregular food intake times for professional reasons (20.2%), dawn phenomenon (15.7%), pregnancy (12.3%), requirement of very low insulin doses (8.9%), and gestational diabetes (0.9%). HbA1c decreased by between 0.6% and 0.9%, and fructosamine by between 5.1% and 12.26%. Nine percent of patients experienced hypoglycemia weekly, 24% every two weeks, and 48% monthly. No hypoglycemia occurred in 19% of patients. Only 10% had neuroglycopenic symptoms. Hypoglycemia unawareness was found in 21%. Hypoglycemia was more common at treatment start, and its frequency rapidly decreased thereafter.ConclusionCSII therapy provides a better glycemic control than MDII treatment. Specific patient training and fine adjustment of insulin infusion doses are required to prevent hypoglycemic episodes, which are the most common complications, mainly at the start of treatment.     

靶控输注静脉麻醉和腰硬联合麻醉对直肠癌根治术患者免疫功能的影响研究

目的：探讨靶控输注静脉麻醉和腰硬联合麻醉对直肠癌根治术患者免疫功能的影响。方法：选择在我院行直肠癌根治术的72例患者,将其分为观察组和对照组各36例,其中观察组给予靶控输注静脉麻醉,对照组采用腰硬联合麻醉,对两组患者手术时间、术中出血量以及免疫球蛋白水平（IgG、IgA、IgM）、血清白介素-6水平（IL-6）、肿瘤坏死因子α水平（TNF-α）以及T细胞亚群（CD3、CD4）水平进行对比。结果：观察组手术平均时间为（130．5±11．7）min,术中平均出血量为（271.3±37．8）ml,与对照组比较差异均无统计学意义（P〉0．05）;两组IgG、IgA及IgM,在T1、T2、T3及T4时刻水平比较差异均无统计学意义（P〉0．05）;两组IL-6、TNF-α、CD3及CD4在麻醉后较T1时均有明显变化,比较差异均有统计学意义（P〈0．05）,且观察组变化较对照组更为明显,两组比较差异有统计学意义（P〈0．05）。结论：靶控输注静脉麻醉和腰硬联合麻醉对直肠癌根治术患者免疫功能均存在抑制作用,且以抑制细胞免疫功能为主,而腰硬联合麻醉抑制作用较低,值得推广应用。