磁共振弥散加权成像结合三维乳腺数字化断层摄影钙化分数在乳腺良恶性钙化病变鉴别中的诊断价值

  目的  评估磁共振弥散加权成像（DWI）结合三维乳腺数字化断层摄影（DBT）钙化分数对于钙化征象在乳腺良恶性病变诊断的应用价值。  方法  回顾性分析我院118例行乳腺DWI检查和DBT检查的患者，DBT检查发现有钙化征象，其中乳腺癌患者51例，病理类型包括:浸润性导管癌、浸润性导管癌、导管原位癌、髓样癌、浸润性小叶癌、黏液腺癌；乳腺良性病变67例，病理类型包括:纤维腺瘤、腺病、导管内乳头状瘤。对所有患者DBT图像的钙化征象进行钙化评分并且测量相应病变区域的表观扩散系数（ADC）值，分析ADC值、钙化分数及二者联合在乳腺含钙化病变的诊断效能。  结果  乳腺癌组ADC值低于乳腺良性病变组，差异有统计学意义（P < 0.05）；钙化分数高于良性病变组，差异有统计学意义（P < 0.05）。ADC值对诊断乳腺良恶性病变的曲线下面积（AUC）为0.853，钙化分数对诊断乳腺良恶性病变的AUC值为0.855，采用Delong检验得出两种方法对诊断乳腺含钙化病变的良恶性诊断效能一致，差异无统计学意义（P=0.625）。两种方法（钙化分数+ADC值）的Logistic回归分析显示，两种方法相结合的AUC值为0.903，具有很高的诊断效能。将ROC曲线（钙化分数、ADC值、两种方法结合的预测概率）经两两Delong检验结果显示，两种方法结合的ROC与单一ROC的差异有统计学意义（P=0.041、0.022）。  结论  DWI与DBT钙化分数对于钙化征象在乳腺良恶性病变的鉴别诊断效能无差别，两种方法相结合的诊断效能显著高于单一方法，为乳腺含钙化病灶的诊断与鉴别诊断中提供了更加可靠的依据。      

夫西地酸乳膏联合丙酸氟替卡松乳膏治疗湿疹52例临床观察

目的观察夫西地酸乳膏联合丙酸氟替卡松乳膏治疗湿疹的临床疗效及安全性。方法通过随机数字表法将入选的102例湿疹患者随机分为两组,治疗组52例,用夫西地酸乳膏和丙酸氟替卡松乳膏交替外涂于皮疹处,间隔时间约为1h,早、晚各一次。对照组50例,单用丙酸氟替卡松乳膏外搽,疗程14d。结果治疗组治疗第7天和第14天时有效率分别为50.00%为80.76%;对照组分别为46.00%和62.00%。仅治疗第14天时差异有统计学意义(P0.05)。治疗过程中均未出现严重的不良反应,未经特殊处理均于1~5d消失。结论夫西地酸乳膏联合丙酸氟替卡松乳膏治疗湿疹效果较好,且无明显不良反应。     

Unexpected Return for Follow-up During the First Year of Multidisciplinary Care May Be Predictive of Rapid Deterioration of Renal Function

Multidisciplinary predialysis education and team care (MDC) may slow the decline in renal function in patients with chronic kidney disease (CKD). However, associations between unexpected return during MDC and progression of renal dysfunction have not been characterized in patients with CKD. Our study aimed to determine the association between exacerbation of renal dysfunction and the frequency of unexpected return during follow-up.A total of 437 patients with CKD receiving multidisciplinary care between January 2009 and June 2013 at the Shin-Kong Wu Ho-Su Memorial Hospital were included in this retrospective observational cohort study, and multiple imputations were performed for missing data. The predictor was the frequency of unexpected return for follow-up during the first year after entering MDC. Main outcome was monthly declines in estimated glomerular filtration rates (eGFR). Moreover, the demographic data, comorbidities, history of medication, and routine laboratory data for patients with CKD were collected.Among all patients, 59.7% were male, the mean age at initiation of MDC was 69.4 ± 13.2 years, and the duration of follow-up was 21.4 ± 3.3 months. The subjects were divided into 2 groups according to frequencies of follow-up (≤4 and > 4 visits) during the 1st year of MDC. The patients with CKD were regularly followed up every 3 months as a part of MDC in our hospital, and patients who returned for more than 4 follow-up visits were included in the unexpected return group. In crude regression analyses, unexpected return was significantly associated with higher monthly declines of eGFR (β = 0.092, 95% confidence interval, 0.014–0.170). This association remained after adjustments for multiple variables, and subgroup analyses of unexpected return showed that male gender, older age, CKD stage 1 to 3, hypertension, history of coronary artery disease, and use of renin–angiotensin system blockade were significantly associated with declines in renal function.In conclusion, unexpected return for follow-up during the 1st year of MDC was significantly associated with the deterioration of renal function.     

25(OH)D水平对高血压合并冠心病患者心肌重构及左心室舒张功能的影响

目的分析25羟基维生素D[25(OH)D]水平对高血压合并冠心病患者心肌重构及左心室舒张功能的影响。方法选择80例高血压合并冠心病患者,根据左心室质量指数及左心室舒张功能分为心肌重构组和无心肌重构组、舒张功能障碍组和无舒张功能障碍组。Logistic回归分析影响高血压合并冠心病患者心肌重构及左心室舒张功能的独立危险因素,ROC曲线分析其诊断效能。结果与无心肌重构组比较,心肌重构组收缩压、总胆固醇(TC)、低密度脂蛋白胆固醇(LDLC)升高,25(OH)D降低(P＜0.05)。与无舒张功能障碍组比较,舒张功能障碍组体质指数(BMI)、25(OH)D水平降低,LDLC升高(P＜0.05)。25(OH)D是患者心肌重构及左心室舒张功能的危险因素(P＜0.05)。25(OH)D水平对患者心肌重构、舒张功能障碍有较好的诊断效能。结论25(OH)D水平是影响高血压合并冠心病患者心肌重构及左心室舒张功能的独立危险因素,早期检测其水平有助于临床诊疗。     

依维莫司联合全反式维甲酸逆转急性早幼粒细胞白血病细胞耐药的研究

目的探讨依维莫司联合全反式维甲酸(简称维甲酸)逆转急性早幼粒细胞白血病(APL)细胞株NB4-R1耐药的作用。方法应用CD11b染色流式细胞术及硝基四唑氮蓝(NBT)还原实验检测两药联合应用对细胞分化的影响, 流式细胞术检测细胞周期情况, Annexin V/PI双染色检测细胞凋亡情况, 蛋白质印迹法检测自噬相关蛋白微管结合蛋白轻链3(LC3)、Beclin 1及早幼粒白血病-维甲酸受体融合蛋白(PML-RARα)、磷酸化核糖体S6激酶(P-P70S6K)、磷酸化4E结合蛋白1(P-4E-BP1) 等表达水平。结果与维甲酸组比较, 联用组能诱导耐药细胞株NB4-R1细胞的分化, 并将细胞增殖阻止在G ₁期而对细胞凋亡无明显影响。100 nmol/L依维莫司组、1μmol/L维甲酸组、联用组、对照组NB4-R1细胞培养48 h后分化百分率分别为(2.29±0.57)%、(17.06±2.65)%、(54.47±4.91)%、(2.54±0.53)%; 处于G ₁期的细胞百分率分别为(35.20±11.97)%、(33.54±6.25)%、(53.70±8.73)%、(27.40±6.01)%; 四组细胞凋亡细胞百分率分别为(2.30±0.14)%、(2.25±0.21)%、(2.40±0.28)%、(1.95±0.07)%。与维甲酸组比较, 联用组mTOR信号通路下游的P70S6K、4E-BP1分子磷酸化水平下降, LC3-II和Beclin 1的表达上调, 且能部分降解融合蛋白PML-RARα。 结论依维莫司联合维甲酸能诱导NB4-R1细胞分化, 且能阻滞细胞周期而不致细胞凋亡, 其机制可能与依维莫司联合维甲酸抑制mTOR信号通路激活自噬作用从而降解PML-RARα蛋白有关。     

Necroptotic TNFα-Syndecan 4-TNFα Vicious Cycle as a Therapeutic Target for Preventing Temporomandibular Joint Osteoarthritis

Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR).     

针刺辅助治疗难治性肠易激综合征临床试验方案关键点设计的思考＊

肠易激综合征（Irritable bowel syndrome，IBS）是临床常见病、多发病，其治疗方法丰富，但部分患者疗效欠佳，发展成难治性IBS。目前国内外关于针灸治疗难治性IBS的临床随机对照试验尚不多见。本文立足试验方案设计的“PICOS”原则，从研究对象及诊断标准、干预措施、对照措施、结局指标四个方面入手，重点探讨针刺辅助治疗难治性肠易激综合征临床试验设计的关键要点。从选择特色优势病种、明确诊断标准、制定符合临床实际的干预方案、运用符合目标的安慰针刺、结合研究设计和目的选定结局指标几个角度，阐述试验相关环节设计的原因和思考。     

纯化痘病毒筛选的常用方法

痘病毒是自然界普遍存在的DNA病毒，能够高效表达外源基因，诱导较强的细胞免疫和体液免疫，受到基因治疗学者的广泛关注。痘病毒发生同源重组的概率较低，所以有效地筛选和纯化痘病毒十分重要。目前常用的筛选重组痘病毒方法有基于CRISPR进行筛选；根据报告基因GFP、LacZ、GPT等进行筛选；利用TK^-和Brdu结合荧光进行筛选；利用药物抗性基因与荧光或显色基因融合，即可在药物筛选的同时观察荧光或显色基因表达情况。本文旨在对目前常用的痘病毒的筛选纯化方法进行综述。