Volume 133 · Issue 19 · 2020

根据国际癌症研究机构的全球癌症统计数据库GLOBOCAN 2018，乳腺癌是女性最常诊断的癌症。^[1]2018年，全球报告了超过200万例新乳腺癌病例，年龄标准化发病率（ASR）为每10万人46.3例，估计超过60万人死于乳腺癌，ASR为每10万人13.0例。乳腺癌病例数持续增加。在中国，2015年新增确诊病例超过27万例，死亡病例7万例。^[2]2018年，全国新增病例增至36.79万例。^[1]因此，我们迫切需要更多关于乳腺癌最佳疗法的临床研究和专家共识。

术语非酒精性脂肪性肝病（NAFLD）是在1980年创造的，用于描述一种类似于酒精性脂肪性肝病的疾病，该疾病发生在没有过量酒精摄入史的患者中。^[1]在形态学上，NAFLD的特征是在没有已知肝病原因（如酒精、自身免疫性肝病、病毒性肝炎等）的情况下肝脏的过量脂肪浸润。NAFLD的临床表现（肝脏和肝外）取决于其主要驱动因素之间复杂相互作用的结果，包括不良的生活习惯和饮食、功能失调的微生物群、遗传易感性和导致代谢功能障碍和肝病的环境线索。然而，将所有具有明显不同临床病程的患者置于NAFLD保护伞下掩盖了其复杂性，并暗示了同质的疾病状态，从而对临床管理和对发病机制的更深入理解产生了负面影响。随着目前对脂肪肝疾病谱的认识的进步，很明显，40年前过时的术语NAFLD不再能有效地描述高度异质性的疾病。正如我们今天所理解的，这种疾病不仅影响饮酒和不饮酒的患者，而且通过充当疾病调节剂，潜在地影响所有患有任何形式肝病的患者。^[2]

After radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function.

A multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function.

Two hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P < 0.001). A greater length of the resected vagina and chemoradiotherapy were common risk factors for LBC and DO, while radiotherapy exerted a stronger effect than chemotherapy. Additionally, patients who received chemoradiotherapy frequently developed a DMCC. The follow-up time was not correlated with bladder storage function.

A nerve-sparing procedure without longer resected vagina is recommended for protecting the bladder storage function.

The standard treatment for pediatric differentiated thyroid carcinoma (DTC) still requires consideration because of a lack of clinical evidence. The purpose of this study was to summarize the clinical experiences and explore the risk factors for post-operative recurrence through a retrospective analysis to develop better clinical strategies for pediatric DTC.

This study retrospectively analyzed children and adolescents with DTC who were treated between January 1999 and December 2014 at the Cancer Hospital, Chinese Academy of Medical Sciences. Clinicopathological results and outcomes were collected. A log-rank test of Kaplan-Meier curves and the Cox regression model were used to determine the factors associated with recurrence.

Data of 150 patients were collected in this study. During the follow-up, there was only one disease-related death. The recurrence rates at 3, 5, and 10 years were 13.6%, 18.7%, and 28.6%, respectively. There was a significant difference in the rate of recurrence according to age (P < 0.001), extrathyroidal extension (P < 0.001), lymph node metastasis (P = 0.023), and invasion of the trachea and esophageal wall (P = 0.004). Cox regression analysis demonstrated that age (P = 0.006) and extrathyroidal extension (P = 0.013) were significant dependent factors of post-operative recurrence.

The prognosis of DTC in children and adolescents is favorable. A close follow-up is recommended because of the high recurrence rate. A comparatively higher recurrence rate was observed in the younger age group, and new age-based divisions may be needed to conveniently evaluate the possibility of recurrence.

B-cell activating factor (BAFF) is vital for B cell survival. Serum BAFF levels are elevated in thrombotic antiphospholipid syndrome, but little is known about levels in patients with positive antiphospholipid antibodies (aPLs) and previous adverse pregnancy outcomes (APOs). We aimed to analyze serum BAFF concentrations of these patients in early pregnancy along with different pregnancy outcomes.

Thirty-six pregnant patients positive for aPLs and previous APOs (patient group), 25 healthy pregnant females (HP group) and 35 healthy non-pregnant females (HNP group) from the Peking University Third Hospital, between October 2018 and March 2019, were enrolled in this study. Serum of HNP and serum of patients as well as HP in the first gestational trimester were collected. Enzyme-linked immunosorbent assay kits were used to measure serum BAFF and interferon-alpha (IFN-α) concentrations. Cytometric bead array analysis was used to measure serum concentrations of cytokines. The patient group was further divided into APOs and non-APOs (NAPOs) group, fetal loss and live birth group according to pregnancy outcomes. The Mann-Whitney U-test was used to assess significance between and within groups. Spearman rank-order was used to evaluate correlation coefficients between BAFF and related cytokines.

The serum BAFF level in HP group was significantly lower than HNP group (245.24 [218.80, 265.90] vs. 326.94 [267.31, 414.80] pg/mL, Z = -3.966, P < 0.001). The BAFF level was obviously elevated in patient group compared to that in HP group (307.77 [219.86, 415.65] vs. 245.24 [218.80, 265.90] pg/mL, Z = -2.464, P = 0.013). BAFF levels in APOs group tended to be higher than that in NAPOs group (416.52 [307.07, 511.12] vs. 259.37 [203.59, 375.81] pg/mL, Z = -2.718, P = 0.006). Compared to HP group, concentrations of IFN-α, interleukin (IL-6) and tumor necrosis factor were higher in patient group (33.37 [18.85, 48.12] vs. 13.10 [6.85, 25.47] pg/mL, Z = -2.023, P = 0.043; 39.16 [4.41, 195.87] vs. 3.37 [2.92, 3.90] pg/mL, Z = -3.650, P < 0.001; 8.23 [2.27, 64.46] vs. 1.53 [1.25, 2.31] pg/mL, Z = -3.604, P < 0.001, respectively). Serum BAFF levels had a positive correlation with the concentrations of both IL-6 and IL-10 (IL-6: r = 0.525, P = 0.002; IL-10: r = 0.438, P = 0.012).

Serum BAFF levels are increased in patients with positive aPLs and previous APOs as compared to healthy pregnant females and tend to be higher in individuals with current APOs. The BAFF levels have a positive correlation with serum IL-6 and IL-10.

Coronary atherosclerotic plaque could go through rapid progression and induce adverse cardiac events. This study aimed to evaluate the impacts of smoking status on clinical outcomes of coronary non-target lesions.

Consecutive patients with coronary heart disease who underwent two serial coronary angiographies were included. All coronary non-target lesions were recorded at first coronary angiography and analyzed using quantitative coronary angiography at both procedures. Patients were grouped into non-smokers, quitters, and smokers according to their smoking status. Clinical outcomes including rapid lesion progression, lesion re-vascularization, and myocardial infarction were recorded at second coronary angiography. Multivariable Cox regression analysis was used to investigate the association between smoking status and clinical outcomes.

A total of 1255 patients and 1670 lesions were included. Smokers were younger and more likely to be male compared with non-smokers. Increase in percent diameter stenosis was significantly lower (2.7 [0.6, 7.1]% vs. 3.5 [0.9, 8.9]%) and 3.4 [1.1, 7.7]%, P= 0.020) in quitters than those in smokers and non-smokers. Quitters tended to have a decreased incidence of rapid lesions progression (15.8% [76/482] vs. 21.6% [74/342] and 20.6% [89/431], P= 0.062), lesion re-vascularization (13.1% [63/482] vs. 15.5% [53/432] and 15.5% [67/431], P= 0.448), lesion-related myocardial infarction (0.8% [4/482] vs. 2.6% [9/342] and 1.4% [6/431], P= 0.110) and all-cause myocardial infarction (1.9% [9/482] vs. 4.1% [14/342] and 2.3% [10/431], P= 0.128) compared with smokers and non-smokers. In multivariable analysis, smoking status was not an independent predictor for rapid lesion progression, lesion re-vascularization, and lesion-related myocardial infarction except that a higher risk of all-cause myocardial infarction was observed in smokers than non-smokers (hazards ratio: 3.00, 95% confidence interval: 1.04-8.62, P= 0.042).

Smoking cessation mitigates the increase in percent diameter stenosis of coronary non-target lesions, meanwhile, smokers are associated with increased risk for all-cause myocardial infarction compared with non-smokers.

Data on the evolution of recent small sub-cortical infarcts are limited, especially in the Chinese. Previous studies have reported a large heterogeneity in cavitation and infarct location; therefore, the present study assessed the morphology of small subcortical infarcts in the basal ganglia in a Chinese cohort.

Patients who had experienced a recent, single, small sub-cortical infarct in the basal ganglia and received at least one follow-up magnetic resonance imaging (MRI) scan were retrospectively identified from January 2014 to June 2018. Time to follow-up imaging, baseline infarct size, vascular risk factors, and other clinical data, as well as the morphologic changes of the index infarct and surrounding white matter were recorded. Demographic, clinical and MRI characteristics were respectively compared among three groups (white matter hyper-intensitie [WMH] vs. cavitation vs. absent) and between with and without new WMH formation groups. In addition, logistic regression analyses were performed in investigating the determinate independent predictors for new WMH formation.

Seventy-eight subjects were included with a median follow-up time of 304 days (range: 124-552 days). We found a significant reduction in infarct size at follow-up: 46 of 78 (59.0%) infarctions showed some degree of cavitation, 19 of 78 (24.4%) index lesions resembled non-cavitated WMH, and 13 of 78 (16.7%) infarcts had disappeared at follow-up MRI. No factors were found to be associated with differential outcomes of the infarcts. In addition, 8 of 78 (10.3%) patients demonstrated new WMH formation surrounding the index infarct; white matter progression (odds ratio = 15.95, 95% confidence interval = 1.65-153.99; P = 0.017) was an independent risk factor of new WMH formation.

More than half of the small sub-cortical infarcts in the basal ganglia progressed to cavities, demonstrating that these infarcts can be reduced and go undetected. The presence of new WMH around the infarct may be indicative of the worsening progression of cerebral small vessel diseases. Additionally, white matter progression is an independent risk factor, which may be a potential therapeutic target.

In recent years, visual quality has been extensively investigated in various conditions. In this community-based population study, we analyzed the effects of aging, refraction, and Lens Opacification Classification System III (LOCSIII) score on retinal imaging quality in healthy Chinese adults.

This cross-sectional study was conducted on sub-group subjects from The Handan Eye Study between October 2012 and January 2013. Healthy subjects over 30-years-old with logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) less than 0 were included. Retinal image quality was measured by optical quality analysis system (OQAS) and recorded as modulation transfer function cutoff frequency (MTF_cutoff), OQAS value (OV) 100%, OV20%, OV9%, Strehl ratio (SR), and objective scatter index (OSI). The correlation between age, spherical equivalent refraction (SE), LOCSIII score, and optical quality parameters were investigated by multivariate analysis.

Among 1108 verified subjects, 690 subjects (1380 eyes) met the inclusion criteria. Their age ranged from 30 to 76 years, SE ranged from -4.75 to 2.75 D. They were divided into five age groups (30-39, 40-49, 50-59, 60-69, and ≥70 years) for further analysis. After multivariate analysis by mixed-effect linear model, SR (t = -3.03, P = 0.002), OV20% (t = -2.39, P = 0.017), and OV9% (t = -3.16, P = 0.001) significantly decreased with the increasing age, whereas logMAR BCVA (t = 4.42, P < 0.001) and OSI (t = 4.46, P < 0.001) significantly increased with age. As SE increased, SR (t = 2.74, P = 0.01), OV20% (t = 2.31, P = 0.02), and OV9% (t = 2.79, P = 0.005) significantly elevated, and OSI (t = -3.38, P < 0.001) significantly decreased. With the increase in cortical opacity score, all optical quality parameters except for SR significantly decreased, including MTF_cutoff (t = -2.78, P = 0.01), OV100% (t = -2.78, P = 0.005), OV20% (t = -2.60, P = 0.009), and OV9% (t = -2.05, P = 0.04). As posterior sub capsular opacity score increased, MTF_cutoff (t = -2.40, P = 0.02) and OV100% (t = -2.40, P = 0.01) significantly decreased, while OSI (t = 7.56, P < 0.001) significantly increased.

In healthy Chinese adult population, optical quality-related parameters significantly decrease with the increasing age, and OSI significantly increases with age. In normal BCVA subjects, optical quality is significantly impacted by cortical and posterior sub capsular opacity rather than by nuclear opacity.

Interleukin-18 (IL18) gene polymorphisms are related to many inflammatory and autoimmune diseases. However, a correlation analysis between IL18-607C/A and -137G/C gene polymorphisms and Takayasu arteritis (TA) is lacking.

This study enrolled 200 patients with TA as the case group and 334 region-, age-, and sex-matched healthy subjects as the control group. We genotyped alleles and genotypes at positions -607 and -137 of the IL18 gene and analyzed the distribution frequencies. Mann-Whitney U test, t test, Chi-squared test and Hardy-Weinberg equilibrium were performed.

After adjusting for risk factors, the adjusted odds ratios and 95% confidence intervals at position -607C/A were 0.533, 0.391 to 0.880 (P = 0.010); 0.266, 0.586 to 1.002 (P = 0.051); and 0.122, 0.552 to 1.420 (P = 0.613) under the dominant, additive, and recessive models, respectively. For the -137G/C polymorphism, the adjusted odds ratios and 95% confidence intervals were 1.571, 1.068 to 2.311 (P = 0.022); 1.467, 1.086 to 1.980 (P = 0.012); and 1.815, 0.901 to 3.656 (P = 0.095) under the dominant, additive, and recessive models, respectively. Moreover, regardless of the model used, we found no statistical difference in distribution frequency between the active and quiescent states of TA for the -607C/A (P = 0.355, 0.631, and 0.705, respectively) and -137G/C polymorphisms (P = 0.205, 0.385, and 0.208, respectively).

The IL18-607C/A gene polymorphism may decrease the risk of TA, and thus is a protective factor, whereas -137G/C may increase the risk of TA, and thus is a risk factor. However, neither polymorphism was related to activity (active vs. quiescent) of TA.

Topoisomerase II alpha (TOP2A) has been reported to play a crucial role in the tumorigenesis of various cancer types. However, the biological role of TOP2A in gallbladder cancer (GBC) remains unknown. The current study aimed to explore the function and potential mechanism of TOP2A in GBC.

Based on Gene Expression Profiling Interactive Analysis data, we found TOP2A was significantly up-regulated in GBC tissues and resulting in shorter overall survival. Quantitative real-time polymerase chain reaction and immunohistochemistry were conducted to detect the expression of TOP2A in 45 pairs of GBC tissues and adjacent non-tumor tissues. In vitro, cell proliferation, migration, and invasion ability were examined by cell counting kit-8 and transwell assay, respectively. Epithelial-mesenchymal transition (EMT) related and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway-related markers were measured by Western blotting. Xenograft model assay was performed to evaluate the effect of TOP2A in vivo.

TOP2A was found up-regulated in GBC (tumor vs. normal, 12.62 vs. 0.34) and correlated with the late tumor node metastasis stage (P = 0.0032), present of lymph node metastasis (P = 0.0273), and poor prognosis in GBC patients (log-rank P = 0.028). In vitro and in vivo assays showed that knockdown of TOP2A notably inhibited cell proliferation, migration, invasion, EMT process, and tumor growth in GBC. In addition, TOP2A down-regulation significantly decreased the protein levels of phosphor (p)-PI3K, p-Akt, and p-mTOR.

Our study demonstrates that TOP2A was overexpressed in GBC and associated with poor prognosis in GBC patients. TOP2A promotes GBC cell proliferation, migration, invasion, EMT process, and tumor growth through activating PI3K/Akt/mTOR signaling pathway, and may serve as a novel prognostic biomarker and therapeutic target for GBC.

粪便微生物群移植（FMT）的方法和相关结果在世界各地的中心之间差异很大。因此，方法学标准化可以改善FMT的临床实践和试验。来自15个城市的22家医院或研究所的28名专家组成的小组为目前关于洗涤微生物群移植（WMT）的共识做出了贡献。^[1]该共识为WMT的方法提供了指导，该方法不同于最近专家共识或建议中的手动FMT。^[2,3]根据他们的专业知识，所有专家被分配到以下五组：第1组，供体筛选；第2组，洗涤微生物群方案、储存和运输；第3组，患者准备；第4组，交付决策；第五组，安全和管理。每一项声明和以下评论都通过了德尔菲程序和面对面的全体会议。根据建议评估、发展和评价系统的分级对现有最佳证据进行了评估。

在过去的几十年里，经济的快速增长和生活方式的转变导致了中国糖尿病患病率的快速上升。由于中国糖尿病肾病（DKD）的预防和管理缺乏标准流程，北京大学医学部组织肾脏病学和内分泌学领域专家制定了DKD中国共识声明。该共识强调循证调查，重点关注以下三个主题：（1）DKD发病和进展的危险因素；（2）DKD的诊断及肾活检指征；（3）DKD的整体管理。

梅毒，由梅毒螺旋体亚种苍白球(T.苍白球），是一种通过性接触传播的慢性、全身性人类疾病。梅毒在我国的发病率和流行率仍然很高。^[1]为了指导该疾病的预防措施和管理，我们更新了梅毒诊断和治疗指南[补充文件，http://links.lww.com/CM9/A292]。梅毒各阶段的表现和诊断见表1，以及管理表2.

肺癌脑转移（BM）在肿瘤发展过程中并不少见。诊断为BM的患者在不接受放疗的情况下，总生存期（OS）仅为3.6个月。随着BM治疗的快速发展，可以实现约16个月的中位生存期(MST)。^[1]对于表皮生长因子受体突变或间变性淋巴瘤激酶基因重排的患者，相应的药剂已被批准用于治疗。在没有驱动基因突变的患者中，放射治疗仍然是BM的标准方案。

门静脉高压症（PHT）是肝硬化严重并发症的触发因素，包括食管胃静脉曲张出血（EVB）、腹水、肝性脑病、肝硬化心肌病、急性肾损伤和肝肾综合征（AKI-HRS），这些并发症可能导致死亡或增加肝移植的需要。^[1,2]其中，EVB仍然是PHT最致命的并发症之一。到目前为止，最广泛接受的评估门静脉压力（PP）和PHT的方法是通过经颈静脉-肝静脉球囊导管插入术的肝静脉压力梯度（HVPG）。^[3]PHT的药物治疗旨在减少PP和预防PHT相关并发症。^[4,5]鉴于PP由门静脉血流和肝血管阻力决定，^[4]目前使用的药物主要是靶向调节增加的肝血流量，如减少高动力循环、肾素-血管紧张素-醛固酮系统激活、血管增生和侧支循环形成，或降低血管内阻力，如抑制肝纤维化、再生结节和血管生成。^[6]在PHT的情况下，动脉血管舒张发生在内脏和体循环中，因此激活神经体液和血管收缩系统，这导致钠和水潴留、血容量增加和心输出量增加。^[7]特利加压素、生长抑素(SMT)或奥曲肽和非选择性β受体阻滞剂(NSBB)通过内脏血管收缩减少门静脉流入。然而，血管活性物质与收缩细胞之间的串扰常导致肝脏微循环异常和PHT的发生。^[6]这些可能是未来PHT药物治疗的新靶点。

脑损伤，如创伤性脑损伤和中风，是世界范围内导致死亡和长期残疾的重要原因。^[1]炎症可能在脑损伤后的继发性损伤中起重要作用。神经干细胞是具有自我更新能力的多能细胞。最初假设NSCs移植通过直接结构细胞替代促进组织修复。然而，这种观点在过去十年中已经被重新调整。旁观者效应提供免疫调节、神经营养和修复支持可能起主要作用。^[2]然而，NSCs发挥免疫调节作用的具体作用方式仍然是一个知识的缺乏。一方面，CD200、CX3趋化因子配体1（CX3CL1）、NSC衍生的外来体（NSC-Exos）的分泌和核苷酸寡聚化结构域（NOD）样受体蛋白3（NLRP3）的调节可以抑制小胶质细胞的炎症作用。另一方面，全身免疫应答的变化也在免疫调节过程中起作用。本文将着重从这些方面探讨NSCs潜在的免疫调节机制。

尽管有研究者假设新辅助化疗可能会改善乳腺癌患者的预后，因为它可以让他们更早地接受全身治疗，但没有大型随机对照试验证实这一假设。因此，普遍认为接受乳腺癌新辅助或辅助化疗的患者在无病生存期(DFS)或总生存期(OS)方面没有差异。^[1,2]卡拉扬尼斯等人^[3]2017年发表了一篇文章，引发了一些争议，因为它报道了新辅助化疗促进了乳腺癌向血管和肺部的微转移，基于对多瘤病毒中间T抗原小鼠模型和人类异种移植物的研究体内并且在固定的组织中。

硬皮病是一种自身免疫性纤维化病症，可进一步亚分类为局限性硬皮病(LSc)和系统性硬化症(SSc)。LSc的特征是硬化性和色素性皮肤病变，而SSc是涉及许多器官的更普遍的结缔组织病症。SSc的特征是真皮胶原束增厚、纤维化和内脏器官中的血管异常。^[1]尽管它们的形态学特征和临床表现不同，但这两种疾病确实有一些共同的特征，包括内皮细胞功能障碍、免疫激活期间辅助性T细胞2（Th2）优势和皮肤过度纤维化，具有相似的病理学发现，导致SSc和LSc共享潜在发病机制的假设。目前，多条证据表明遗传因素可能有助于SSc易感性。^[2]人白细胞抗原（HLA）基因与SSc易感性密切相关，研究描述了SSc和SSc之间的一些相关性HLA-B,HLA-C,HLA-DRA,HLA-DRB1,HLA-DRB5,HLA-DQA1,HLA-DQB1,HLA-DMB,HLA-DOA,HLA-DPA1,HLA-DPB1，和HLA-DPB2。^[2]大量非HLA也有报道称基因与SSc的发展相关，这些基因包括结缔组织生长因子基因（TGF）、信号转导子和转录基因激活子（STAT4）等[补充表1，http://links.lww.com/CM9/A294]。然而，这些结果中只有一部分可以在其他研究中得到验证，在中国人群中的类似研究仍然极其有限。有趣的是，像白细胞介素1（IL-1）、ras同源家族成员B（RHOB）、序列相似性167成员A-BLK原癌基因家族（FAM167A-BLK),STAT4、干扰素调节因子5基因(IRF5),HLA-DPB1和角蛋白1（KRT1）均与中国人群中的SSc易感性相关。^[3]尽管已有报道LSc倾向于表现出某种形式的家族遗传，但尚未明确鉴定出该疾病的可遗传特征。此外，据我们所知，没有研究调查LSc和SSc的共同遗传因素。因此，检查LSc的易感性并确定SSc和LSc的遗传谱之间是否存在任何相关性将是非常重要的。本研究旨在确定LSc患者的遗传谱以及中国人群中SSc和LSc的任何共同遗传特征。此外，本研究评估了先前描述的SSc基因座在中国人群中的发生情况，并将其频率与其他种族社区中报道的频率进行了比较。

尽管经皮冠状动脉介入治疗（PCI）和抗血栓治疗取得了重大进展，但支架内再狭窄（ISR）仍然是PCI后具有挑战性的临床问题。确定ISR风险分层的新参数和潜在的药理学靶点非常重要。我们之前回顾了中性粒细胞与淋巴细胞比率（NLR）可能是血细胞几个参数中ISR的最佳预测因子。2型糖尿病（T2DM）与炎症密切相关，是ISR的独立危险因素。然而，很少有研究评估NLR的动态变化对T2DM患者ISR的预测作用。因此，我们旨在分析第一次PCI和第二次冠状动脉造影（CAG）中的术前NLR值，并评估其对T2DM患者ISR的预测价值。

48%至69%的患者在开颅术后48小时内经历中度至重度疼痛。^[1]不受控制的疼痛会增强交感神经激活，这可能会升高动脉和颅内压并导致颅内出血。目前，阿片类药物常用于术后镇痛。然而，阿片类药物有希望的镇痛作用是以术后恶心和呕吐发生率增加为代价的。非甾体抗炎药通常不给药，主要是因为担心颅内出血。术前切口浸润和头皮神经阻滞是临床执行的策略^[2];然而，支持这两种策略治疗益处优越性的证据有限。目前，缺乏有效、安全、简单和非侵入性的方法来治疗或预防开颅术后疼痛。

外来体是一类膜囊泡，其直径约为50至100nm；它们从各种细胞释放到细胞外基质中。^[1]外来体富含蛋白质、脂质和核酸。据报道，它们参与各种生理过程，是细胞间物质和信息交流的重要工具。^[2,3]越来越多的证据表明，外来体可以从人唾液、尿液、血液和其他体液中提取。^[4]然而，乳头分泌物中是否存在外来体仍然未知。在这项研究中，使用超速离心从乳腺癌患者的乳头分泌物和产后妇女的初乳中分离外来体。通过透射电子显微镜（TEM）、蛋白质印迹和纳米颗粒跟踪分析（NTA）鉴定外来体。详细方法见http://links.lww.com/CM9/A286.补充文件1。本研究由山东大学齐鲁医院伦理委员会批准（编号：KYLL-2018-096），所有患者均提供了书面知情同意书。

致编辑：持续性三叉神经动脉（PTA）是最常见的残余胎儿吻合之一。在胚胎发育期间，颈动脉和椎基底循环之间的联系通常会退化。颈动脉夹层（CAD）是年轻人脑缺血的常见原因，可由基因突变引起的高同型半胱氨酸血症（HHcy）引起。我们报告一例由CAD引起的后循环缺血。

致编辑：反向痤疮（AI），也称为化脓性汗腺炎，是一种慢性复发性炎症性皮肤病，其特征是深部疼痛性结节和脓肿，产生的疤痕主要分布在摩擦间区域。γ-分泌酶(GS)基因的功能丧失突变是家族性AI的原因。^[1]GS是一种跨膜蛋白酶，由四个必需蛋白亚基组成：一个催化早老素亚基(PSEN)和三个辅因子亚基(nicastrin[NCSTN]、早老素增强子2[PSENEN]、前咽缺陷1)。GS参与多种I型膜蛋白的切割，包括淀粉样前体蛋白和Notch蛋白。PSENEN直接与PSEN结合，是其自催化裂解和蛋白酶活性所必需的。迄今为止，已报告了六种突变PSENEN所有这些都导致移码截短和改变的蛋白质产物，主要导致单倍体不足。^[2]银屑病是一种遗传决定的增殖和炎症实体，由异常角质形成细胞增殖和分化与T淋巴细胞介导的免疫过程之间的复杂相互作用引起。Dowling-Degos病（DDD）是一种罕见的常染色体显性疾病，其特征是进行性网状色素沉着过度和小的深棕色角化过度丘疹，主要影响弯曲区域。^[3]在此，我们报告了一个三代中国汉族艾氏家族的先证者和其他三名成员分别同时患有银屑病和DDD。

致编辑：碰撞肿瘤是罕见的肿瘤，包括两个细胞群，这两个细胞群彼此并置发育，很少或没有混合区域。^[1]据报道，发生碰撞肿瘤的最常见部位包括肺、颅骨、直肠、肝脏、子宫、膀胱和睾丸。^[2,3]然而，食管碰撞肿瘤的生物学行为在很大程度上仍然未知，只有少量源自病例报告的研究已发表。本研究报告5例食管碰撞肿瘤，为未来患者的护理提供循证建议。

致编辑：肺动脉狭窄可由多种因素引起，如法洛四联症、肺动脉闭锁、三尖瓣闭锁伴肺动脉狭窄、闭锁合并另一种先天性心脏病和肺循环发育不良，^[1,2]威廉综合征和阿拉吉勒综合征。此外，肺动脉分支狭窄可能是一些遗传代谢疾病的结果，如先天性风疹。^[3]大多数肺动脉狭窄病例需要手术干预。

致编辑：患者男，25岁，主诉右颈部有肿大结节3个月，无疼痛、瘙痒或皮炎。患者自2016年起患有布加综合征（BCS），2017年接受介入治疗（血管成形术伴支架置入术）及后期适当处理后得到良好控制。患者无高血压或糖尿病病史。患者右颈部出现椭圆形皮下肿胀。查体发现肿块边界清楚，与邻近组织无粘连，测量直径2.5 cm。血压和心率分别为128/84 mmHg和76次/min。