星点设计-效应面法优化丁香苦苷聚乳酸-羟基乙酸纳米粒的制备工艺

目的优化丁香苦苷聚乳酸(Syr)-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]纳米粒(Syr-NPs)的处方。方法采用纳米沉淀法制备Syr-NPs,以包封率、载药量、平均粒径以及总评"归一值"为评价指标,采用星点设计-效应面法考察PLGA质量浓度(A)、丁香苦苷质量浓度(B)、水相与有机相比例(C)3因素考察对包封率、载药量、平均粒径以及总评归一值的影响,以星点设计-效应面法选取最佳处方条件进行预测分析。结果最优处方工艺为PLGA质量浓度为9.63 mg/mL,Syr质量浓度为12.88 mg/mL,有机相与水相的比例为1∶9.46,制得的Syr-NPs的包封率、载药量、平均粒径分别为(27.86±0.87)%、(7.02±0.15)%、(110.0±1.20)nm。结论该方法稳定可行,可用于优化包载Syr的PLGA纳米粒处方与制备工艺。     

急性胰腺炎患者血清FABP4、miR-369-5p表达与疾病严重程度的关系

目的 检测急性胰腺炎(AP)患者血清中脂肪酸结合蛋白4(FABP4)、微小RNA-369-5p(miR-369-5p)水平,并探讨二者对AP病情程度的评估价值.方法 选取2019年4月至2020年6月于本院就诊治疗的127例AP患者为研究对象,根据严重程度将其分为轻症AP(MAP)组69例和重症AP(SAP)组58例.采用实时荧光定量PCR(qRT-PCR)检测血清miR-369-5p水平,采用酶联免疫吸附(ELISA)法检测血清FABP4、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、C-反应蛋白(CRP)水平;采用Pearson法分析AP患者血清FABP4、miR-369-5p水平与生化指标及疾病严重程度评分相关性;采用受试者工作特征曲线(ROC曲线)分析血清FABP4、miR-369-5p水平对SAP的诊断价值;采用Logistic回归分析影响AP病情程度的因素.结果 SAP组血清FABP4、TNF-α、IL-6、CRP水平及Ranson评分、急性生理与慢性健康状况评分Ⅱ(APACHEⅡ)评分高于MAP组,miR-369-5p水平低于MAP组(P<0.05).AP患者血清FABP4与miR-369-5p呈负相关(r=-0.541,P<0.05);FABP4与TNF-α、IL-6、CRP水平及Ranson评分、APACHEⅡ评分呈正相关(P<0.05);miR-369-5p与TNF-α、IL-6、CRP水平及Ranson评分、APACHEⅡ评分呈负相关(P<0.05).血清FABP4、miR-369-5p水平诊断SAP的曲线下面积(AUC)分别为0.877、0.867,特异性分别为91.3％、76.8％,灵敏度分别为72.4％、87.9％;二者联合诊断的AUC为0.933,特异性为87.0％,灵敏度为89.7％.FABP4是AP患者出现重症的危险因素(P<0.05),miR-369-5p是AP患者出现重症的保护因素(P<0.05).结论 血清FABP4、miR-369-5p水平与AP病情程度密切相关,可作为早期诊断AP患者病情程度的良好参考指标.     

Revision of failed metal-on-metal total hip arthroplasty using cemented arthroplasty: a mean 10-year follow-up of 157 consecutive patients

ObjectiveThis study was performed to assess the outcomes of Asian patients who underwent conversion from metal-on-metal total hip arthroplasty (MoM-THA) to cemented THA (CTHA).MethodsOne hundred and fifty-seven consecutive patients (157 hips) who underwent CTHA following primary MoM-THA from January 2005 to February 2015 were retrospectively analysed. The primary endpoints were the clinical outcomes. Follow-ups occurred at 3 months, 6 months, 1 year, 2 years, and then every 2 years following revision of MoM-THA.ResultsThe mean follow-up after conversion was 10 years (range, 5–14 years). Statistically significant improvements in the mean Harris hip score were observed between the preoperative and final follow-up evaluations (62.71 ± 13.85 vs. 84.03 ± 16.21, respectively). The major orthopaedic complication rate was 16.5% (26/157). Six (3.8%) patients underwent revision at a mean of 3.5 ± 1.3 years after conversion, predominantly because of prosthesis loosening or recurrent dislocation. Nine (5.7%) patients developed prosthesis loosening at a mean of 2.6 ± 1.1 years following conversion, two of whom requested revision surgery. Eleven (7.0%) patients developed prosthesis dislocation, four of whom requested revision surgery.ConclusionCTHA may yield favourable functional outcomes and a reduced rate of major orthopaedic complications.     

“干针”的由来

笔者通过对现已发表的涉及"干针"的中文文献进行整理,观察到现有文章或是侧重"干针与针灸之争"的热点报道,或着眼"肌筋膜理论"探讨"干针"的作用机制或临床应用,但尚无对"干针"由来的论述。另有涉及其起源的部分文章,均一带而过,无详细阐述。"干针"最先是作为对照组的一种刺激方法而设立,本文通过梳理"干针"起源的背景,以反思"干针"与针刺的关系。     

Loss of GRB2 associated binding protein 1 in arteriosclerosis obliterans promotes host autophagy

Background:Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy.Methods:In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1.Results:The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t = 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t = 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein.Conclusion:Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.     

Transforming brain signals related to value evaluation and self‐control into behavioral choices

The processes involved in value evaluation and self‐control are critical when making behavioral choices. However, the evidence linking these two types of processes to behavioral choices in intertemporal decision‐making remains elusive. As the ventromedial prefrontal cortex (vmPFC), striatum, and dorsolateral prefrontal cortex (dlPFC) have been associated with these two processes, we focused on these three regions. We employed functional magnetic resonance imaging during a delayed discounting task (DDT) using a relatively large sample size, three independent samples. We evaluated how much information about a specific choice could be decoded from local patterns in each brain area using multivoxel pattern analysis (MVPA). To investigate the relationship between the dlPFC and vmPFC/striatum regions, we performed a psychophysiological interaction (PPI) analysis. In Experiment I, we found that the vmPFC and dlPFC, but not the striatum, could determine choices in healthy participants. Furthermore, we found that the dlPFC showed significant functional connectivity with the vmPFC, but not the striatum, when making decisions. These results could be replicated in Experiment II with an independent sample of healthy participants. In Experiment III, the choice‐decoding accuracy in the vmPFC and dlPFC was lower in patients with addiction (smokers and participants with Internet gaming disorder) than in healthy participants, and decoding accuracy in the dlPFC was related to impulsivity in addicts. Taken together, our findings may provide neural evidence supporting the hypothesis that value evaluation and self‐control processes both guide the intertemporal choices, and might provide potential neural targets for the diagnosis and treatment of impulsivity‐related brain disorders.     

Pathological classification and prognosis of renal damage caused by antineutrophil cytoplasmic antibody associated vasculitis

Objective To analyze the pathological characteristics and prognostic factors of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods A retrospective analysis of AAV patients with renal biopsy results admitted to Kidney Disease Center of the First Affiliated Hospital from January 2004 to February 2017 was performed. The patients were divided into 4 types according to Berden classification, and their clinical, pathological characteristics and prognosis were compared. The survival curves of each type of patients were plotted by Kaplan-Meier method, and the difference of survival curves was compared using Log-rank test. With entering the maintenance dialysis as the endpoint, Cox regression was used to analyze the prognostic factors. Results A total of 175 patients with AAV, including 59 cases (33.7%) of focal type, 39 cases (22.3%) of crescent type, 32 cases (18.3%) of sclerosis type, 45 cases (25.7%) of mixed type. The basal serum creatinine levels in crescent type group and sclerosis type group were significantly higher than those in the focal type group or mixed type group (all P＜0.05), and loop necrosis rate in sclerosis type group was significantly lower than chat in the focal type group or crescent type group (both P＜0.05). The median follow-up period was 11.8 (0.5-86.7) months. The event-free survival rates were 83.1%, 77.8%, 64.1% and 50.0% in the focal type, mixed type, crescent type and sclerotic type groups (Log-rank χ2=11.537, P=0.009). Cox regression analysis showed higher parathyroid hormone (HR=1.013, 95%CI 1.007-1.019, P＜0.001), glomerular sclerosis ≥50% (HR=10.532, 95%CI 2.903-38.203, P＜0.001) were independent risk factors for AAV patients entering maintenance dialysis, and higher estimated glomerular filtration rate (HR=0.943, 95%CI 0.896-0.993, P=0.025) was protective factor. Conclusion The prognosis of AAV renal damage is worsened according to focal, mixed, crescent and sclerosis types. Lower estimated glomerular filtration rate, higher parathyroid hormone and glomerular sclerosis ≥50% are independent risk factors for AAV patients entering maintenance dialysis.     

Variant analysis and genotype/phenotype association study in 42 Chinese patients with Bartter syndrome type 3

Objective To analyze the variants of 42 Chinese patients with Bartter syndrome type 3 (BS3) and explore the characteristics of genotype and phenotype. Methods Forty-two genetically diagnosed patients from 40 Han and one Hui families were collected in the Affiliated Hospital of Qingdao University and the Affiliated Qingdao Municipal Hospital of Qingdao University during the period of June 2012 to October 2018. The second-generation sequencing and multiplex ligase probe-dependent amplification (MLPA) technique were used to analyze the CLCNKB gene variation and its characteristics in children with BS3. The clinical data were collected, and the therapeutic effect and growth improvement were observed and followed up. Thirty eight patients were divided into severe (n=26) and light (n=12) groups according to the severity of genetic variation. The clinical phenotypic characteristics of the two groups were compared. Results Thirty-six variants including 16 novel ones of CLCNKB gene were found. The whole gene deletion of CLCNKB gene was the most frequent mutation (40%), and the rate of large deletions was up to 55%. The most common symptoms included development retardation (38/42), polydipsia and polyuria (35/42), constipation (31/42) and vomiting (27/42). All patients presented with hypokalemia, hypochloremia and metabolic alkalosis. After the medicine treatment that based on indomethacin and potassium chloride, most patients could achieve obvious recovery of growth rate and restoration of hypokalemia. The severe group showed more severe metabolic alkalosis than the light group. Conclusions Thirty-six variants of CLCNKB gene have been found in this study, including 16 novel ones, which enrich the human gene mutation database (HGMD) and provide valuable references to diagnosis, treatment and the genetic counseling of Chinese population.     

基于中药质量标志物和传统用法的中药饮片标准汤剂传承发展研究思路与建议

中药汤剂(也称煎剂)是中医师最常用的中药复方剂型,也是中药历史上应用最久和最广的制剂。药材是饮片的原料,饮片是制备提取物、构成中医处方和中药制剂的原料,更体现了传承发展中药的重要性。基于中药饮片标准汤剂,科学认识汤剂质量,提高药典饮片和中成药质量评价研究理论和方法是科学发展的重要策略。开展以中医药理论为指导、临床应用为基础的中药饮片标准汤剂研究,基于中药质量标志物理论和研究方法探讨饮片和煎煮工艺的影响,形成标准汤剂的质量评价体系,既有利于确保中医处方用药的安全和疗效,也有利于认识标准汤剂在"药材-饮片-中成药"的质量及其标准的差异和价值,提升国家对中药饮片监管水平,保障人民用药安全和有效;还有利于认识标准汤剂在中药饮片生产、中药配方颗粒及经典名方的传承研发中的重要意义。