医疗器械可沥滤物安全性研究（三）：允许限量建立

随着新材料、新设计等创新性医疗器械产品的不断涌现,可沥滤物的安全性研究也面临新的挑战,其中可沥滤物允许限量的建立是医疗器械安全性评价研究的重要方面。结合现有产品的审评,简述高分子医疗器械可沥滤物安全性研究中允许限量的建立环节中的常见问题,并对其原因进行解析,供相关机构及研发人员参考使用。     

Analysis of the myoelectric characteristics of genioglossus in REM sleep and its improvement by CPAP treatment in OSA patients

Sleep and Breathing - To reveal the characteristics of genioglossus (GG) activation in moderate and severe obstructive sleep apnea (OSA) patients during rapid eye movement (REM) sleep compared with...     

NPM1, FLT3-ITD,CEBPA, and c-kit mutations in 312 Chinese patients with de novo acute myeloid leukemia

Objectives

To explore NPM1, FLT3-ITD, CEBPA, and c-kit mutations in patients with acute myeloid leukemia (AML) from Chinese population.

Methods

In this study, we retrospectively analyzed the prevalence and clinical pro?le of NPM1, FLT3-ITD, CEBPA, and c-kit mutations in 312 patients with de novo AML.

Results

The frequencies of NPM1, FLT3-ITD, c-kit, and CEBPA mutations were 15.4, 14.0, 7.64, and 25.6%, respectively. The occurrence rate of NPM1 mutations increased with age in patients younger than 60 years. NPM1, c-kit, and CEBPA mutations were all associated with French-American-British subtypes. Patients with NPM1 mutations and FLT3-ITD presented with higher peripheral white blood cell counts and marrow blast percentages.

Conclusion

Both this and previous studies may suggest low frequencies of NPM1 and FLT3-ITD mutations in AML patients from the Chinese population, and they may have a synergistic function in stimulating proliferation of leukemia cells.     

Noninvasive central pulse pressure is an independent determinant of renal function

The purpose of this study was to investigate the prognostic properties of different BP measurements for renal function decrement and early chronic kidney disease (CKD) in community‐dwelling populations with normal renal function at baseline. A total of 1426 participants were included and followed for a median of 4.8 years (interquartile range, 4.5‐5.2), and central hemodynamic profile and estimated glomerular filtration rate (eGFR) were evaluated. One main outcome was the rapid eGFR decline defined as a decline in eGFR of greater than 3 mL/min per 1.73 m² per year; the other was the new incidence of CKD. At the end of follow‐up, mean eGFR decreased from 93.39 ± 13.46 mL/min per 1.73 m² to 85.72 ± 14.81 mL/min per 1.73 m², and the incidence of rapid eGFR decline and CKD were 20.7% and 5.6%, respectively. In multivariate linear regression analysis, central pulse pressure (PP), age, fasting blood glucose, and concentration of homocysteine were independent determinants of the change in renal function. Not only in the prediction of rapid eGFR decline but also in the incident of CKD, baseline central PP was the only BP component that consistently independently associated with both outcomes after adjustment for various confounders. When compared with subjects in the lowest quartile of central PP, those in the highest quartile demonstrated a significantly increased risk of CKD (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.08‐2.96; P = .006). The study showed that central PP emerged as an independent predictor of the decline in renal function.     

Peak blood pressure‐guided monitoring may serve as an effective approach for blood pressure control in the out‐of‐office setting

We aimed to explore whether diurnal blood pressure (BP) peak characteristics have a significant influence on the association between left ventricular damage with the two BP components (morning BP vs. afternoon peak BP) in untreated hypertensives. This cross‐sectional study included 1084 hypertensives who underwent echocardiography and 24‐h ambulatory BP monitoring. Participants were stratified according to the relationship between morning systolic BP (MSBP; average SBP within 2 h of waking up) and afternoon peak systolic BP (ASBP; average SBP between 16:00 and 18:00). Afternoon and morning hypertension was defined as ≥ 135/85 mm Hg. The morning and afternoon peak BPs occurred at around 7:00 and 17:00, respectively. In general hypertensives, morning BP and afternoon peak BP are significantly different in absolute values (for binary SBP, McNemar''s χ² = 6.42; p = .014). ASBP was more pronounced than MSBP in 602 patients (55.5%), in whom 24‐h SBP showed higher consistency with ASBP than with MSBP (Kappa value: 0.767 vs 0.646, both p < .01). In subjects with ASBP ≥ MSBP, ASBP was associated with left ventricular hypertrophy independent of MSBP (logistic regression analysis odds ratio: 1.046, p < .01), and left ventricular mass index was more strongly correlated with ASBP than with MSBP (multiple regression coefficient β: 0.453, p < .01), in which the relationships held true independently of 24‐h SBP. The opposite results were obtained in subjects with MSBP > ASBP. Peak BP‐guided monitoring may serve as an effective approach to out‐of‐office hypertension monitoring and control, providing the best consistency with 24‐h average SBP and highest discrimination performance for target organ damage, independently of 24‐h SBP.     

Relationship between high‐normal albuminuria and arterial stiffness in Chinese population

High‐normal albuminuria is related to the morbidity and mortality of cardiovascular disease. Arterial stiffness has been regarded as a predictor of cardiovascular disease. However, the relationship between high‐normal albuminuria and arterial stiffness is uncertain in Chinese population. A total of 1343 Chinese participants (aged 58.9 ± 12.1 years, 63.53% male) were included in this study. High‐normal albuminuria was defined as urinary albumin‐to‐creatinine ratio (UACR) above the median within normal albuminuria. Based on the level of UACR, all participants were divided into low‐normal albuminuria group (UACR < 6.36 mg/g, n = 580), high‐normal albuminuria group (6.36 mg/g ≤ UACR < 30 mg/g, n = 581), microalbuminuria (30 mg/g ≤ UACR < 300 mg/g, n = 162), and macroalbuminuria (UACR ≥ 300 mg/g, n = 20). Arterial stiffness was assessed by measuring carotid‐femoral pulse wave velocity (cfPWV). With the increment of UACR, the level of cfPWV was increased gradually (P < .001). Stepwise multiple regression analysis showed that systolic blood pressure, age, serum creatinine, heart rate, logarithmic (LG)‐transformed UACR, and fasting plasma glucose were independently associated with cfPWV in all subjects (P < .001). LG‐UACR was found to be related to cfPWV in high‐normal albuminuria and macroalbuminuria subjects. After further stratification in the high‐normal albuminuria subjects, their relation remained in male, elderly over 65 years old, or normotensives. In summary, UACR is associated with arterial stiffness in subjects with proteinuria excretion in high normal level. High‐normal albuminuria might be an early indicator of arterial stiffness, especially in male, elderly, or normotensives in Chinese population. Furthermore, age and blood pressure are still observed to be the most important risk factor of arterial stiffness.     

人二倍体细胞2BS株和KMB17株在疫苗研发中的应用

人二倍体细胞是WHO认可的更安全的疫苗生产用细胞基质,已成为全世界疫苗生产首选的细胞基质。我国自主研制的二倍体细胞KMB17株和2BS株来源于人胚肺细胞,因其无致癌性、无外源因子污染,且细胞性状比较稳定,越来越多地在人用疫苗研发与生产中使用。由于KMB17细胞和2BS细胞对多种病毒具有敏感性,因此也作为细胞基质被应用于许多病毒性疫苗的研究开发。目前,用这两种人二倍体细胞生产的疫苗,包括甲型肝炎疫苗、脊髓灰质炎疫苗和肠道病毒71型灭活疫苗等,已在我国大量上市。     

二甲双胍联合利拉鲁肽对棕榈酸诱导的内皮细胞氧化损伤具有协同保护作用

目的 探讨二甲双胍和利拉鲁肽在改善棕榈酸诱导的人脐静脉内皮细胞氧化损伤方面是否具有协同保护效应.方法 分离培养人脐静脉内皮细胞,应用不同浓度棕榈酸处理诱导细胞氧化损伤,观察不同浓度二甲双胍和（或）利拉鲁肽对细胞氧化损伤的影响.流式细胞仪检测细胞内的活性氧簇（ROS）水平,硝酸还原酶法检测上清一氧化氮（NO）的水平,组间比较采用单因素方差分析和Q检验.结果 与对照组相比,0.25和0.50 mmoL/L棕榈酸细胞内ROS水平显著升高[（125±17）％、（189±8）％比100％,P＜0.05],上清NO水平降低[（89.9±6.2）％、（79.8±4.8）％比100.0％,P＜0.05];二甲双胍（0.5 ～ 1.0 mmol/L）和利拉鲁肽（10 ～ 100 nmol/L）单独应用后,可使0.50 mmol/L棕榈酸所致的ROS产生增加和NO产生减低作用下降;低剂量的二甲双胍（0.1 mmol/L）或利拉鲁肽（3 nmoL/L）单独应用对0.5 mmol/L棕榈酸的作用均无明显的影响,但两者联合则可减低上述作用：两者联合组与棕榈酸组相比,ROS水平降低[（158±31）％比（250±27）％,P＜0.05],NO水平增加[（91.7±30.6）％比（82.3±5.0）％,P＜0.05].结论 二甲双胍和利拉鲁肽在改善棕榈酸诱导的内皮细胞氧化损伤方面具有协同效应.