Theoretical Investigation of Chitosan-Assisted Controlled Release of Digestive System Antitumor Drug Fluorouracil

5-Fluorouracil (5-FU) has been applied to treat pancreatic cancer, which is one of the most common types of digestive system tumors. However, due to poor tumor selectivity, 5-FU's therapeutic effect has certain limitations. 5-FU's activity and selectivity against tumor cells can be improved by chitosan assisted drug delivery systems. Understanding the atomic interaction mechanism between chitosan and 5-FU is important. In this work, the interactions between 5-FU and different types of chitosan were systematically investigated by using molecular dynamics (MD) simulation. Based on the radial distribution function and the free energy calculation, our results demonstrate that the functional groups of chitosan could greatly regulate the interaction behavior between chitosan and 5-FU. Moreover, 5-FU could gradually release from chitosan at a more acidic pH (tumor tissues) environment. These results revealed the underlying atomic interaction mechanism between 5-FU and chitosan at various pH levels, and may be helpful in the design of chitosan-based drug delivery systems.     

提高重症患者气管插管医护配合默契度的效果研究

目的:通过持续质量改进的实施与效果评价,提高重症患者气管插管医护配合默契度。方法:应用PDCA进行重症患者气管插管医护配合的现状分析、实施改进措施、数据查检,比较PDCA实施前后医护配合默契度及医生对护士操作配合的满意度。结果:实施PDCA后医护配合默契度(90.00±9.07)分,高于实施前(60.00±14.95)分(P<0.05);医生对护士操作配合的Likert scale 5分满意度评分,4分以上占97.14%,高于实施前77.14%(P<0.05)。结论:通过持续质量改进,可以增进医护沟通,对重症患者气管插管进行科学管理,提高医护配合默契度,提高抢救效率,保证患者生命安全。     

基于网络药理学的济脉通片降压机制研究

目的 采用网络药理学阐明济脉通片多成分-多靶点-多途径的作用理念，为进一步研究济脉通片降压药效物质基础和机制提供一定理论参考。方法 通过TCMSP数据库，结合口服利用度（≥ 30%）和类药性分析（≥ 0.18）参数，筛选济脉通片的活性成分；通过Drugbank和TCMSP数据库进行靶点预测分析；通过GENCARD数据库筛选出高血压疾病相关基因；结合DAVID和KEGG数据库进行GO分析和通路分析；使用Cystoscope软件构建"化合物-靶点-作用通路"网络图。结果 经筛选后得到济脉通片的33个化合物，148个潜在靶基因并映射到了223条信号通路，其中31条信号通路与高血压的发生发展密切相关，其中AGE-RAGE signaling pathway in diabetic complications、PI3K-Akt signaling pathway、TNFsignaling pathway、Adrenergic signaling in cardiomyocytes和Focal adhesion为重要的通路枢纽。结论 济脉通片主要通过多成分、多靶点、多通路调节血管内皮功能、炎症反应、钙钠离子转运、糖脂代谢等参与血管舒张、改善炎症、调节机体代谢、调节离子转运等而产生降压作用。     

人参多糖对晚期肺癌化疗疗效及MDSCs、Treg细胞、免疫因子水平的影响

目的 分析人参多糖对晚期非小细胞肺癌(NSCLC)化疗疗效及髓系抑制细胞(MDSCs)、调节性T细胞(Treg细胞)、免疫因子水平的影响。 方法 选取2014年6月—2015年12月浙江省人民医院收治的晚期NSCLC患者63例，随机分为人参多糖组和对照组。应用GP或DP方案化疗，人参多糖组加用人参多糖注射液。比较2组临床疗效、生活质量及不良反应，比较MDSCs、Treg细胞和两者相关性，比较精氨酸酶和细胞因子(VEGF、TGF-β、IL-10、IFN-γ、TNF-α)水平。 结果 人参多糖组疾病控制率及生活质量均明显高于对照组(均P<0.05)。人参多糖组白细胞减少和恶心呕吐发生率明显低于对照组(均P<0.05)。治疗前2组MDSCs、Treg细胞百分比差异无统计学意义(均P>0.05)；治疗后人参多糖组MDSCs、Treg细胞百分比均明显低于对照组(均P<0.05)。Treg细胞与MDSCs呈正相关(P<0.05)。2组治疗前精氨酸酶和细胞因子差异无统计学意义(均P>0.05)；治疗后人参多糖组精氨酸酶、VEGF、TGF-β、IL-10较对照组均明显降低(均P<0.05)，IFN-γ、TNF-α均明显升高(均P<0.05)。 结论 人参多糖可通过影响MDSCs、Treg细胞及免疫因子，改善晚期NSCLC化疗患者的免疫功能，提高疗效和生活质量，同时能有效减轻化疗不良反应。      

Expert recommendations on blood purification treatment protocol for patients with severe COVID-19

Coronavirus disease (COVID-19) was first diagnosed in Wuhan in December 2019. The World Health Organization defined the subsequent outbreak of COVID-19 worldwide as a public health emergency of international concern. Epidemiological data indicate that at least 20% of COVID-19 patients have severe disease. In addition to impairment of the respiratory system, acute kidney injury (AKI) is a major complication. Immune damage mediated by cytokine storms and concomitant AKI is a key factor for poor prognosis. Based on previous experience of blood purification for patients with severe acute respiratory syndrome and Middle East respiratory syndrome combined with clinical front-line practice, we developed a blood purification protocol for patients with severe COVID-19. This protocol is divided into four major steps. The first step is to assess whether patients with severe COVID-19 require blood purification. The second step is to prescribe a blood purification treatment for patients with COVID-19. The third step is to monitor and adjust parameters of blood purification. The fourth step is to evaluate the timing of discontinuation of blood purification. It is expected that blood purification will play a key role in effectively reducing the mortality of patients with severe COVID-19 through the standardized implementation of the present protocol.     

Prenatal exposure to di-n-butyl phthalate (DBP) differentially alters androgen cascade in undeformed versus hypospadiac male rat offspring

This study was to compare the alterations of androgen cascades in di-n-butyl phthalate (DBP)-exposed male offspring without hypospadias (undeformed) versus those with hypospadias. To induce hypospadias in male offspring, pregnant rats received DBP via oral gavage at a dose of 750 mg/kg BW/day during gestational days 14–18. The mRNA expression levels of genes downstream of the androgen signaling pathway, such as androgen receptor (AR) and Srd5a2, in testes of undeformed rat pups were similar to those in controls; in hypospadiac rat pups these levels were significantly lower than those of control pups. In contrast, both undeformed and hypospadiac rats had decreased serum testosterone levels, reduced mRNA expression of key enzymes in the androgen synthetic pathway in the testes, and ablated genes of developmental pathways, such as Shh, Bmp4, Fgf8, Fgf10 and Fgfr2, in the genital tubercle (GT) as compared to those in DBP-unexposed controls, albeit hypospadiac rats had a more severe decrement than those of undeformed rats. Although other possibilities cannot be excluded, our findings suggest that the relatively normal levels of testosterone-AR-Srd5a2 may contribute to the resistance to DBP toxicity in undeformed rats. In conclusion, our results showed a potential correlation between decreased testosterone levels, reduced mRNA expression of AR and Srd5a2 and the occurrence of hypospadias in male rat offspring prenatally exposed to DBP.     

Acute toxicity when concentration varies with time: A case study with carbon monoxide inhalation by rats

Exposure to time-varying concentrations of toxic compounds is the norm in both occupational settings and daily human life, but little has been done to investigate the impact of variations in concentration on toxic outcomes; this case study with carbon monoxide helps fill that gap. Median acute lethality of 10-, 20-, 40-, and 60-min continuous exposures of rats to carbon monoxide was well described by the toxic load model (k = Cⁿ × t; k is constant, C = test concentration, n = toxic load exponent, and t = exposure duration) with n = 1.74. Dose response-relationships for 1-h exposures including a recovery period between 10- or 20-min pulses showed greater similarity (in both median lethality and steepness of dose-response curve) to continuous exposures with equivalent pulse duration and concentration, rather than a 60-min exposure with equivalent time-weighted average concentrations or toxic load. When pulses were of unequal concentration (3:1 ratio), only the high concentration pulse contributed to lethality. These findings show that fluctuations or interruptions in exposure over a short time scale (60 min or less) can have a substantial impact on outcomes (when n > 1), and thus high-resolution monitoring data are needed to aid interpretation of resulting outcomes.     

Indocyanine green retention is a potential prog-nostic indicator after splenectomy and pericar-dial devascularization for cirrhotic patients

BACKGROUND: Splenectomy and pericardial devasculariza-tion (SPD) is an effective treatment of upper gastrointestinal bleeding and hypersplenism in cirrhotic patients with portal hypertension. Indocyanine green retention at 15 minutes (ICGR15) was reported to offer better sensitivity and speciifc-ity than the Child-Pugh classiifcation in hepatectomy, but few reports describe ICGR15 in SPD. The present study was to evaluate the prognostic value of ICGR15 for cirrhotic patients with portal hypertension who underwent SPD.
METHODS: From January 2012 to January 2015, 43 patients with portal hypertension and hypersplenism caused by liver cirrhosis were admitted in our center and received SPD. The ICGR15, Child-Pugh classiifcation, model for end-stage liver disease (MELD) score, and perioperative characteristics were analyzed retrospectively.
RESULTS: Preoperative liver function assessment revealed that 34 patients were Child-Pugh class A with ICGR15 of 13.6%-43.0% and MELD score of 7-20; 8 patients were class B with ICGR15 of 22.8%-40.7% and MELD score of 7-17; 1 patient was class C with ICGR15 of 39.7% and MELD score of 22. The optimal ICGR15 threshold for liver function com-pensation was 31.2%, which offered a sensitivity of 68.4% and a speciifcity of 70.8%. Univariate analysis showed preopera-tive ICGR15, MELD score, surgical procedure, intraoperative blood loss, and autologous blood transfusion were signiifcant-ly different between postoperative liver function compensated and decompensated groups. Multivariate regression analysis revealed that ICGR15 was an independent risk factor of post-operative liver function recovery (P=0.020).
CONCLUSIONS: ICGR15 has outperformed the Child-Pugh classiifcation for assessing liver function in cirrhotic patients with portal hypertension. ICGR15 may be a suitable prognos-tic indicator for cirrhotic patients after SPD.