Nicotine and smoking: Effects upon subjective changes in mood

A Mood Adjective Check List and an activation scale were used to measure subjective reports on mood changes in 24 male habitual smokers before and after smoking cigarettes with known content of nicotine, at different times of day and rates of puffing. Ratings on pleasantness were dose related. Aggression and anxiety showed effects attributable to circadian influence and slight decreases in both factors occurred after smoking the highest nicotine cigarette. The MACL scores were greatly affected by the experimental procedure. Levels of inner tension were found related to the nicotine inhaled. The heuristic value of the concept of activation in these studies is suggested.This work was supported by the Tobacco Research Council, and carried out at the Institute of Psychiatry, London.     

Effectiveness,nephrotoxicity, and therapeutic drug monitoring of polymyxin B in nosocomial pneumonia among critically ill patients

ObjectivesWe aimed to assess the effectiveness and nephrotoxicity of polymyxin B in critically ill patients with nosocomial pneumonia and to evaluate the utility of its therapeutic drug monitoring (TDM).MethodsWe retrospectively analyzed patients who received polymyxin B treatment for ≥48 h since the establishment of polymyxin B TDM in a 26‐bed tertiary referral intensive care unit. Univariate and multivariate analyses were conducted to assess the variables associated with polymyxin B effectiveness and nephrotoxicity.ResultsA total of 62 patients were enrolled. Most (56.5%) of the patients performed TDM, 54.3% of them reached the therapeutic target of area under curve across 24 h at steady state (AUC_ss,24h) of 50–100 mg h L⁻¹, and 10 patients had an AUC_ss,24h value of <50 mg h L⁻¹. Thirty‐six (58.1) and 31 (50.0%) patients had favorable clinical and microbiological responses, respectively. Reaching the therapeutic target of AUC_ss,24h (odds ratio [OR] = 13.15, p = 0.015), a favorable microbiological response (OR = 40.80, p = 0.00), and complicated with septic shock (OR = 0.12, p = 0.021) were independently associated with favorable clinical outcomes of polymyxin B treatment. The incidence of acute kidney injury (AKI) was 45.2%. A lower creatinine clearance (OR = 0.96, p = 0.008) and concomitant treatment with loop diuretics (OR = 5.93, p = 0.046) were predictive of nephrotoxicity.ConclusionOur findings show that TDM of polymyxin B is a valuable intervention, and the achievement of its optimal pharmacodynamic target can improve treatment outcome. Renal insufficiency and concomitant treatment with loop diuretics were found to be associated with the risk of nephrotoxicity.     

天玑骨科机器人联合O臂导航系统辅助经皮微创治疗骨盆后环损伤

目的评价天玑骨科机器人联合O臂导航系统辅助经皮微创治疗骨盆后环损伤的疗效。方法回顾分析2016年1月—2021年6月收治的76例骨盆后环损伤患者临床资料，其中45例采用天玑骨科机器人联合O臂导航系统辅助经皮微创骶髂螺钉内固定术治疗（研究组），31例仅在C臂X线机引导下行经皮微创骶髂螺钉内固定术治疗（对照组）。两组患者性别、年龄、致伤原因、骨折Tile分型、受伤至手术时间等一般资料比较差异均无统计学意义（P>0.05）。记录两组患者手术时间、术中出血量、钉道调整次数和术中透视次数，采用Matta评分评价骨折复位质量；末次随访时采用Majeed评分评估患者骨盆功能恢复情况。 结果研究组共植入螺钉72枚，每例患者植入螺钉1（1，2）枚；对照组共植入螺钉47枚，每例患者植入螺钉1（1，2）枚；两组每例患者植入螺钉数比较差异无统计学意义（Z=−0.392，P=0.695）。研究组手术时间、术中出血量、钉道调整次数和术中透视次数均显著少于对照组（P<0.05）。所有患者均获随访，随访时间6～24个月，平均14个月。术后和随访过程中均未见严重并发症。术后1周采用Matta评分评价骨折复位质量，两组差异无统计学意义（Z=−1.135，P=0.256）。末次随访时采用Majeed评分评价骨盆功能，两组差异无统计学意义（Z=−1.279，P=0.201）。 结论天玑骨科机器人联合O臂导航系统辅助治疗骨盆后环损伤是一种可靠的手术方式，与C臂X线机引导下的传统手术方式相比减少了手术时间和透视次数，提高了手术安全性、准确性和手术效率。     

MDA-7/IL-24-HT7融合蛋白的制备及其对肿瘤细胞凋亡的诱导作用

目的：构建MDA-7/IL-24-HT7原核及真核表达质粒,制备MDA-7/IL-24-HT7融合蛋白,研究该融合蛋白在肿瘤细胞内的定位及其对肿瘤细胞致凋亡作用。方法：PCR扩增MDA-7/IL-24基因,插入含有HaloTag (HT7)标签的载体中,构建MDA-7/IL-24-HT7原核及真核表达质粒;MDA-7/IL-24-HT7融合蛋白经IPTG诱导表达后纯化。利用带有荧光标记的HT7配基观察MDA-7/IL-24-HT7在肿瘤细胞内的定位。MTT法及AnnexinV-PI染色法检测MDA-7/IL-24-HT7对肿瘤细胞生长和凋亡的影响。结果：成功构建了表达MDA-7/IL-24-HT7融合蛋白的原核及真核表达质粒,MDA-7/IL-24-HT7融合蛋白主要存在于E.coli BL21的包涵体内。MDA-7/IL-24-HT7融合蛋白定位于肿瘤细胞的内质网上。MDA-7/IL-24-HT7融合蛋白可抑制肿瘤细胞的生长,1 mg/ml MDA-7/IL-24-HT7 融合蛋白作用大肠癌HCT116细胞、肝癌SMMC7721细胞96 h后,细胞凋亡率分别为（34.7±1.3）% 和（22.1±0.9）%,显著高于未处理的肿瘤细胞（P<0.01）。结论：带有HaloTag标签的MDA-7/IL-24-HT7融合蛋白可抑制肿瘤细胞增殖和诱导肿瘤细胞凋亡。     

正常人心率减速力和心率变异性的变化及相关性

目的 测定不同年龄正常人心率减速力与心率变异性并分析其相关性,探讨其临床意义。方法 选取正常人90例,根据年龄将受试者分为青年组和老年组,进行24h动态心电图检查,离线计算DC、HRV时域指标及相关系数。结果 老年组DC和HRV值与青年组比较均降低,差异有统计学意义(P<0.05),且DC和HRV显著相关。结论 DC和HRV时域指标随着年龄的增加而减小,这些无创指标可以反映自主神经功能。     

IL-24对CIK细胞体内杀伤肿瘤细胞活性的影响

目的 研究IL-24对细胞因子诱导的杀伤细胞(CIK)体内杀伤肿瘤细胞活性的影响。方法 (1)从健康人外周血中提取单个核细胞,第一天加入IFN-γ(1 000 IU/mL),第二天加入IL-1(100 IU/mL)、CD3mAb(50 ng/mL)、IL-2(300 IU/mL)诱导CIK细胞,另一组与IL-1、CD3mAb、IL-2同时加入IL-24(1 000 IU/mL);(2)建立HepG₂肿瘤细胞株荷瘤小鼠皮下移植瘤模型,分为五组,每三天分别测量肿瘤大小。结果 IL-24诱导CIK细胞治疗组荷瘤小鼠实体瘤体积小于其它组(P＜0.05)。结论 在CIK细胞诱导过程中加入IL-24能明显增强其体内的抗肿瘤活性,对临床上把CIK细胞用于生物治疗有一定的指导意义。     

Synthesis and immunological characterization of a 134-mer synthetic peptide corresponding to the N-terminal half of the HIV-1 nucleoprotein,p24

A 134-mer peptide corresponding to the N-terminal sequence of p24 (residues 146–279 of the gag gene product of the LAV strain) was chemically synthesized using highly optimised protocols on an ABI 430A synthesizer. The crude peptide was obtained by treating the peptide-resin with HF, then purified by a combination of size exclusion and RP-HPLC. One hundred milligram of 90% pure 134-mer can be obtained within a month. Both mice and rabbit polyclonal antisera raised against a commercial preparation of recombinant p24, and a pooled sera from HIV-1 infected individuals reacted strongly with the 134-mer peptide in ELISA. Both mice and rabbits immunized with the free peptide emulsified in Freund's complete adjuvant generated strong anti-peptide and anti-p24 antibody responses as judged by immunoblots and ELISAs. Immunodominant epitopes were mapped to residues 201–227 (LKETINEEAAEWDRVHPVHAGPIAPG). These B-cell epitopes had previously been identified by mouse monoclonal antibodies raised against HIV-1 virus or gag gene products. Furthermore, murine T-cell lines generated against the 134-mer peptide were found to respond to two short peptides, P24B (residues 195–215) and P24D1 (residues 268–279). These two T-cell epitopes were previously reported as human helper T-cell and CTL epitopes, respectively. These results clearly indicate that the synthetic 134-mer peptide could elicit both T- and B-cell responses to HIV-1 similar to those obtained with the natural viral gag protein, and could be useful for the development of a synthetic HIV vaccine     

Enhanced anti-tumor activity by the combination of a conditionally replicating adenovirus mediated interleukin-24 and dacarbazine against melanoma cells via induction of apoptosis

Malignant melanoma is one of the most lethal and aggressive human malignancies. It is notoriously resistant to all of the current therapeutic modalities, including chemotherapy. Suppressed apoptosis and extraordinary invasiveness are the distinctive features that contribute to the malignancy of melanoma. Dacarbazine (DTIC) has been considered as the gold standard for melanoma treatment with a response rate of 15–20%. Unfortunately, the resistance to this chemotherapeutic agent occurs frequently. ZD55-IL-24 is a selective conditionally replicating adenovirus that can mediate the expression of interleukin-24 (IL-24) gene, which has a strong anti-tumor effect. In this study, we hypothesized that a combination of ZD55-IL-24-mediated gene virotherapy and chemotherapy using DTIC would produce an increased cytotoxicity against human melanoma cells in comparison with these agents alone. Our results showed that the combination of ZD55-IL-24 and DTIC significantly enhanced the anti-tumor activity by more effectively inducing apoptosis in melanoma cells than either agent used alone without any overlapping toxicity against normal cells. This additive or synergistic effect of ZD55-IL-24 in combination with DTIC in killing human malignant melanoma cells implies a promising novel approach for melanoma therapy.     

Solubilization of an active opiate receptor from Bufo marinus

The effect of veratridine on in vitro release of noradrenaline (NA) from ligand cat hypogastric nerve was investigated. After in vivo ligation for 24–48 h, large amounts of NA and dopamine-β-hydroxylase (DBH) accumulated in the nerve segment immediately proximal to the ligature (P₁). In vitro incubation of ligated nerves (segments P₁ and P₂) in oxygenated Krebs solution at 37°C in the presence of veratridine caused a marked and dose-dependent release of endogenously accumulated NA into the incubation medium. The release continued to occur for a considerable time, even after washout of the drug. Veratridine-induced depletion of tissue NA was accounted for by its release, as NA, into the incubating medium. The secretory response to veratridine was readily blocked by tetrodotoxin (TTX). Veratridine-induced release was dependent on calcium and abolished by high magnesium. On the basis of the similarity between the NA secretory response to veratridine in this preparation and in adrenergically innervated organs, the results favour the view that the in vivo-ligated cat hypogastric nerve may serve as a useful model of adrenergic nerve terminals free of effector cells.