Overview of CF lung pathophysiology

Defects of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein affect the homeostasis of chloride, bicarbonate, sodium, and water in the airway surface liquid, influencing the mucus composition and viscosity, which induces a severe condition of infection and inflammation along the whole life of CF patients. The introduction of CFTR modulators, novel drugs directly intervening to rescue the function of CFTR protein, opens a new era of experimental research. The review summarizes the most recent advancements to understand the characteristics of the infective and inflammatory pathology of CF lungs.     

The effect of ethanol or long-time reaction on the diatom test in water samples using sodium hypochlorite

BackgroundThe diatom test method using sodium hypochlorite (NaClO) was equivalent to the conventional method in water samples. However, the method using NaClO was inferior to the conventional method in lung samples, in which ethanol was used and the reaction with NaClO was longer compared with the method in water samples. Using water samples, we aimed to clarify whether these differences affect the diatom test result.Materials and methodsThirteen water samples from natural water sources were each divided into four parts corresponding to four (2 × 2) digestion methods: 3 “digestion” vs. 1 “digestion” and with ethanol vs. without ethanol. After the base-2 logarithmic transformation, the diatom counts were analyzed using three-way analysis of variance (ANOVA); factor 1 was “digestion times,” factor 2 was “ethanol,” and factor 3 was “sample number,” and the interaction between factors 1 and 2 was also analyzed.ResultsThe geometric means of the diatoms from the 3 “digestion” with ethanol method, the 3 “digestion” without ethanol method, the 1 “digestion” with ethanol method, and the 1 “digestion” without ethanol method were 373.5, 551.8, 436.6, and 522.0, respectively. ANOVA showed a significant difference in factor 2 (P = 1.7 × 10^-4). There was no significant difference in factor 1 (P = 0.46), and no significant interaction between factors 1 and 2 (P = 0.13).ConclusionEthanol may decrease the diatom count in the diatom test using NaClO. In contrast, the diatom frustules do not dissolve through three-times digestion using NaClO.     

关节镜清理术联合透明质酸钠治疗膝骨性关节炎的效果

目的探讨关节镜清理术联合透明质酸钠治疗膝骨性关节炎患者的效果。方法100例膝骨性关节炎患者随机分为两组各50例,对照组采用关节镜清理术治疗,实验组采用关节镜清理术联合透明质酸钠治疗,比较两组的关节液炎性因子水平、膝关节功能以及疼痛情况。结果治疗后,实验组的TNF-α、IL-6、IL-8水平均显著低于对照组(P<0.05)。治疗1个月、3个月、6个月后,实验组的Lysholm评分均显著高于对照组,VAS评分均显著低于对照组(P<0.05)。结论关节镜清理术联合透明质酸钠治疗膝骨性关节炎可降低患者关节液炎性因子水平,改善膝关节功能,减轻疼痛。     

Four cases of sodium nitrite suicidal ingestion: A new trend and a relevant Forensic Pathology and Toxicology challenge

Sodium nitrite (NaNO₂) is an inorganic compound commonly used as a food additive, antifreeze admixture, and fertilizer. Its toxicity mechanism is mainly represented by the oxidation of ferrous iron to ferric iron of one of the four heme structures in haemoglobin with the onset of methaemoglobin. The mechanism of death by sodium nitrite toxicity is severe hypoxia. We present four cases of suicidal sodium nitrite ingestion that closely occurred within a two months-period. Self-poisoning with sodium nitrite actually represents an increasing trend in nitrates’ related deaths. In order to reach a precise diagnosis of NaNO₂ intoxication, a complete toxicological analysis should be carried out including not only MetHb blood levels but also nitrites and nitrites in standard or alternative matrices as a routine procedure. Autopsy should be carefully performed to detect common indicators of hypoxia or more rarely evident typical by themselves-non specific signs of sodium nitrite toxicity. Suicidal manner of death should be carefully considered when circumstantial data support that ingestion of large amounts of NaNO₂ occurred as a consequence of a self-injurious behaviour. Relevant informations include victim’s previous Internet or book researches about paths to follow to commit suicide with sodium nitrate, employment and past medical history, with strong regard to psychiatric diseases as well as eventual taking psycotropic drugs.Finally, an accurate integration of autoptic and toxicological results with circumstantial data is necessary to make correct diagnosis of death due to acute respiratory failure secondary to suicidal sodium nitrite ingestion.     

发作性睡病的药物治疗进展

发作性睡病是致残性白天睡眠增多的最常见原因之一，其治疗旨在减少白天睡眠增多和猝倒，改善夜间睡眠紊乱、睡眠瘫痪及与睡眠有关的幻觉。2019年，组胺H3受体拮抗剂替洛利生（Pitolisant）和多巴胺及去甲肾上腺素再摄取抑制剂索利氨酯（Solriamfetol）分别在欧盟和美国上市，前者具有促醒和抗猝倒作用，后者也有促醒作用，且戒断症状和滥用的发生率更低。目前，控释型羟丁酸钠（FT218）、低钠型羟丁酸盐（JZP-258）、选择性去甲肾上腺素再摄取抑制剂（瑞波西汀，又称AXS-12）以及莫达非尼联合氟卡尼制剂（THN102）等药物仍在开发和测试中，均可作为治疗发作性睡病相关白天睡眠增多和猝倒的潜在药物。本文重点介绍这些最近研发的发作性睡病治疗药物。     

丙戊酸钠通过EGFR下调CD44表达抑制胶质瘤细胞生长

目的:探讨丙戊酸钠通过抑制A172胶质瘤细胞表皮生长因子受体（epidermal growth factor receptor，EGFR）的活化，下调CD44表达，进而调节细胞生长的机制。方法:实时荧光定量PCR和Western blot检测A172胶质瘤细胞中CD44以及siRNA下调CD44表达的情况，MTT检测CD44和丙戊酸钠对细胞生长的影响，Western blot检测丙戊酸钠对细胞中p-EGFR、EGFR和CD44表达影响。结果:丙戊酸钠抑制A172胶质瘤细胞生长，并具有浓度依赖性。A172胶质瘤细胞表达CD44，siRNA下调CD44表达后，细胞生长较正常组显著减缓。活化EGFR促进A172胶质瘤CD44蛋白表达，而EGFR的抑制剂Lapatinib可显著抑制上述效应。丙戊酸钠抑制EGFR磷酸化，下调CD44蛋白表达。结论:丙戊酸钠抑制A172胶质瘤细胞的生长。抑制A172胶质瘤细胞中EGFR的活化，下调CD44的表达，是丙戊酸钠抑制胶质瘤细胞生长的其中一个机制。     

Pediatric bowel preparation: Sodium picosulfate,magnesium oxide,citric acid vs polyethylene glycol,a randomized trial

BACKGROUND Bowel preparation in children can be challenging.AIM To describe the efficacy, safety, and tolerability of sodium picosulfate, magnesium oxide, and citric acid(SPMC) bowel preparation in children.METHODS Phase 3, randomized, assessor-blinded, multicenter study of low-volume, divided dose SPMC enrolled children 9-16 years undergoing elective colonoscopy. Participants 9-12 years were randomized 1:1:1 to SPMC ? dose × 2, SPMC 1 dose × 2, or polyethylene glycol(PEG). Participants 13-16 years were randomized 1:1 to SPMC 1 dose × 2 or PEG. PEG-based bowel preparations were administered per local protocol. Primary efficacy endpoint for quality of bowel preparation was responders(rating of ‘excellent' or ‘good') by modified Aronchick Scale. Secondary efficacy endpoint was participant's tolerability and satisfaction from a 7-item questionnaire. Safety assessments included adverse events(AEs) and laboratory evaluations.RESULTS 78 participants were randomized, 48 were 9-12 years, 30 were 13-16 years. For the primary efficacy endpoint in 9-12 years, 50.0%, 87.5%, and 81.3% were responders for SPMC ? dose × 2, SPMC 1 dose × 2, and PEG groups, respectively. Responder rates for 13-16 years were 81.3% for SPMC 1 dose × 2 and 85.7% for PEG. Overall, 43.8% of participants receiving SPMC 1 dose × 2 reported it was ‘very easy' or ‘easy' to drink, compared with 20.0% receiving PEG. Treatment-emergent AEs were reported by 45.5% of participants receiving SPMC 1 dose × 2 and 63.0% receiving PEG.CONCLUSION SPMC was an efficacious and safe for bowel preparation in children 9-16 years, with comparable efficacy to PEG. Tolerability for SPMC was higher compared to PEG.     

嘌呤配体P2X门控离子通道型受体7及其下游分子在痛风性关节炎中作用机制的研究进展

目前随着痛风性关节炎的发病率逐年上升,对该病炎性反应及疼痛机制的研究越来越多,该病主要由尿酸盐沉积及ATP刺激P2X7R、Nod样受体蛋白3、NEK7表达诱导炎性反应递质成熟与分泌所致,但具体机制尚不明确。现对P2X7R、NLRP3、NEK7的国内外研究进展进行综述,以探讨GA炎性反应及疼痛的发病机制,为防治GA提供新思路与治疗靶点。     

PBL结合绘图教学模式在胰腺癌患者肝素钠皮下注射临床教学中的作用

[摘要]目的探讨问题导向学习(PBL)结合绘图教学模式在临床护理带教中的应用效果。方法纳入2016年6月~2017年6月在我院实习的本科护生78名,按等比例随机分为观察组和対照组,观察组采取PBL结合绘图学模式法,对照组采用单纯PBL教学模式,利用统计学方法按照参考指标对两组实习生的考核数据进行对比分。结果观察组理论知识得分明显大于对照组[(90.31±4.55)分vs.(81.30±5.69)分],观察组临床实践技能得分明显大于对照组[(92.21±4.18)分vs.(80.31±5.39)分],差异均有统计学意义(P0.05)。结论PBL结合绘图教学模式临床护理带教中效果显著,比单纯PBL教学模式更具有优势,更有利于培养学生的循证思维与创新能力,提高临护理教学质量,在临床护理带教中值得推广。     

An eco-friendly HPLC-UV method for the determination of risedronate in its bulk and tablet dosage form with application to content uniformity,dissolution and stability testing

Risedronate is a nitrogen-containing bisphosphonate for the treatment and prevention of postmenopausal osteoporosis. The current work aims to develop a novel green HPLC-UV method for the rapid analysis of risedronate sodium in bulk and tablet formulation. The analyzed samples were separated on Waters Atlantis dC18 (150 mm × 3.9 mm; 5 μm) column using a green mobile phase consisting of potassium phosphate buffer pH 2.9 and potassium edetate buffer pH 9.5 in a ratio of 1:2, the final pH was adjusted to 6.8 with phosphoric acid, the mobile phase was pumped at a rate of 1.0 mL/min, with column temperature set at 30 °C, eluted samples were detected at 263 nm and the chromatographic run time was 3.0 min. The method was found to be linear over the concentration range of 14–140 μg/mL with a correlation coefficient (r²) of 0.9994. Accuracy and precision were evaluated from three QC samples (LQC, MQC and HQC) together with the five calibrators where the percentage accuracy was found to be 101.84%. Processed quality control samples of risedronate sodium were tested for stability at different conditions, short term, long term and freeze- thaw stability. The current method was further extended to study the content uniformity of Actonel® tablets following United States Pharmacopoeia (USP) guidelines. The proposed method was fully validated as per ICH guidelines.