Volume 132 · Issue 24 · 2019

Clinical outcomes of undifferentiated arthritis (UA) are diverse, and only 40% of patients with UA develop rheumatoid arthritis (RA) after 3 years. Discovering predictive markers at disease onset for further intervention is critical. Therefore, our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.

We performed a prospective, multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals. Clinical and serological parameters were obtained at recruitment. Follow-up was undertaken in all patients every 12 weeks for 2 years. Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.

A total of 234 patients were recruited in this study, and 17 (7.3%) patients failed to follow up during the study. Among the 217 patients who completed the study, 83 (38.2%) patients went into remission. UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9% vs. 16.8%, χ² = 8.228, P = 0.008), anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7% vs. 10.7%, χ² = 43.897, P < 0.001), and double-positivity rate of RF and anti-CCP antibody (38.1% vs. 4.1%, χ² = 32.131, P < 0.001) than those who did not. Anti-CCP antibody but not RF was an independent predictor for RA development(hazard ratio 18.017, 95% confidence interval: 5.803–55.938; P < 0.001).

As an independent predictor of RA, anti-CCP antibody should be tested at disease onset in all patients with UA.

Despite the growing epidemic of heart failure (HF), there is limited data available to systematically compare noncardiac comorbidities in the young-old, old-old, and oldest-old patients hospitalized for HF. The precise differences will add valuable information for better management of HF in elderly patients.

A total of 1053 patients aged 65 years or older hospitalized with HF were included in this study. Patients were compared among three age groups: (1) young-old: 65 to 74 years, (2) old-old: 75 to 84 years, and (3) oldest-old: ≥85 years. Clinical details of presentation, comorbidities, and prescribed medications were recorded.

The mean age was 76.7 years and 12.7% were 85 years or older. Most elderly patients with HF (97.5%) had at least one of the non-cardiac comorbidities. The patterns of common non-cardiac comorbidities were different between the young-old and oldestold group. The three most common non-cardiac comorbidities were anemia (53.6%), hyperlipidemia (45.9%), and diabetes(42.4%) in the young-old group, while anemia (73.1%), infection (58.2%), and chronic kidney disease (44.0%) in the oldest-old group. Polypharmacy was observed in 93.0% elderly patients with HF. Additionally, 29.2% patients were diagnosed with infection, and 67.0% patients were prescribed antibiotics. However, 60.4% patients were diagnosed with anemia with only 8.9% of them receiving iron repletion.

Non-cardiac comorbidities are nearly universal in three groups but obviously differ by age, and inappropriate medications are very common in elderly patients with HF. Further treatment strategies should be focused on providing optimal medications for age-specific non-cardiac conditions.

The results of the Trial Assigning IndividuaLized Options for Treatment (TAILORx) suggested that approximately 70% of T1-2N0M0, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients can avoid chemotherapy and receive only adjuvant endocrine therapy. We conducted a retrospective analysis of the clinicopathologic features and prognostic factors of patients with breast cancer who met the inclusion criteria of the TAILORx trial.

According to the enrollment criteria of the TAILORx trial, a retrospective analysis was performed on patients with breast cancer who were treated from January 2008 to December 2015 at Peking University First Hospital. The clinicopathologic characteristics of all patients were analyzed, and prognoses were calculated using the Kaplan-Meier method and a Cox proportionate hazards model.

A total of 2430 patients with early stage breast cancer who were admitted at our hospital had complete clinicopathologic data and follow-up information. Of these patients, 722 met the inclusion criteria and were enrolled in the present study, accounting for 29.7% of all patients. Among them, 417 (57.8%) patients received only adjuvant endocrine therapy (the non-chemo group), and 305 (42.2%) patients received adjuvant chemotherapy followed by adjuvant endocrine therapy (the chemo group). No statistically significant difference was observed in overall survival (OS) between the two groups (non-chemo vs. chemo: 5-year OS: 97.9% vs. 97.9%, χ² = 1.00, P = 0.995; hazard ratio [HR] = 1.00, 95% confidence interval [CI]: 0.46–2.21). A significant difference was observed in disease-free survival (DFS) between the two groups (non-chemo vs. chemo: 5-year DFS: 97.9% vs. 94.7%, χ² = 8.65, P = 0.003; HR = 3.05, 95% CI: 1.40–6.67). The choice of adjuvant therapy was associated with clinicopathologic factors, such as the age at diagnosis, T stage, histologic grade, the Ki67 index, the presence of intravascular tumor thrombus (P < 0.001), pathologic type, and menstrual status (P = 0.014).

In the absence of internationally recognized multigene testing methods, for patients with early hormone receptorpositive, HER2-negative breast cancer, clinicians can develop a treatment plan based on clinicopathologic features only, which can effectively screen some patients who do not need adjuvant chemotherapy. However, nearly half of patients still receive adjuvant chemotherapy, and whether these patients can be exempted from chemotherapy warrants further exploration.

Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are important for both the integrated diagnosis and the prognosis of diffuse gliomas. The p.R132H mutation of IDH1 is the most frequently observed IDH mutation, while IDH2 mutations were relatively rarely studied. The aim of the study was to determine the pathological and genetic characteristics of lowergrade gliomas that carry IDH2 mutations.

Data from 238 adult patients with lower-grade gliomas were retrospectively analyzed. The status of IDH1/2 gene mutations, telomerase reverse transcriptase (TERT) promoter mutations, O⁶-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p/19q co-deletion and the expressions of IDH1 R132H, alpha-thalassemia X-linked mental retardation, and p53 were evaluated. Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier estimation using the log-rank test.

Totally, 71% (169/238) of patients were positive for IDH mutations, including 12 patients harboring mutations in IDH2. Among the 12 patients with IDH2 mutations, ten patients harbored the R172K mutation, one patient harbored the R172S mutation and one harbored the R172W mutation. Of these, 11 tumors occurred in the frontal lobe and showed morphology typical of oligodendroglioma. The proportion of grade II tumors was higher than that of grade III tumors in IDH2 mutant-gliomas. IDH2 mutations were frequently associated with TERT promoter mutations, 1p/19q co-deletion and MGMT promoter methylation. IDH2 mutations were associated with better outcomes compared with IDH wild-type gliomas (P < 0.05). However, the PFS and OS did not differ from that of IDH1 mutant patients (P = 0.95 and P = 0.60, respectively).

IDH2 mutations are more frequent in oligodendrogliomas and associated with a better prognosis. IDH2 mutations may segregate in distinct clinico-pathological and genetic subtypes of gliomas, and therefore may merit routine investigation.

Leukocyte telomere has been shown to be related to insulin resistance-related diseases, such as type 2 diabetes mellitus(T2DM) and non-alcoholic fatty liver disease (NAFLD). This cross-sectional study investigated the association of leukocyte telomere length (LTL) with NAFLD in T2DM patients.

Clinical features were collected and LTL was measured by Southern blot-based terminal restriction fragment length analysis in 120 T2DM patients without NAFLD and 120 age-matched T2DM patients with NAFLD. NAFLD was clinically defined by manifestations of ultrasonography. The correlation between LTL and clinical and biochemical parameters were analyzed by Pearson correlation or Spearman correlation analysis. Factors for NAFLD in T2DM patients were identified using multiple logistic regressions.

LTL in T2DM patients with NAFLD were significantly longer than those without NAFLD (6400.2 ± 71.8 base pairs [bp] vs. 6023.7 ± 49.5 bp, P < 0.001), especially when diabetes duration was less than 2 years. Meanwhile, the trend of shorter LTL was associated with the increased diabetes duration in T2DM patient with NAFLD, but not in T2DM patients without NAFLD. Finally, LTL (odds ratio [OR]: 1.001, 95% confidence interval [CI]: 1.000–1.002, P = 0.001), as well as body mass index (OR: 1.314, 95% CI: 1.169–1.477, P < 0.001) and triglycerides (OR: 1.984, 95% CI: 1.432–2.747, P < 0.001), had a significant association with NAFLD status in T2DM patients.

T2DM patients with NAFLD had a significantly longer LTL than those without NAFLD. The longer LTL was especially evident in the early stage of T2DM, indicating that longer LTL may be used as a biomarker for NAFLD in T2DM patients.

The pathogenesis of multiple sclerosis (MS) is mediated primarily by T cells, but most studies of MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have focused on CD4⁺ T cells. The aims of the current study were to determine the pathological interrelationship between CD4 and CD8 autoreactive T cells in MS/EAE.

Female C57BL/6 mice (n =20) were induced by myelin oligodendrocyte glycoprotein (MOG) _35-55 peptide. At 14 days after immunization, T cells were isolated from the spleen and purified as CD4⁺ and CD8 ⁺ T cells by using CD4 and CD8 isolation kits, and then the purity was determined by flow cytometric analysis. These cells were stimulated by MOG_35–55 peptide and applied to proliferation assays. The interferon-gamma (IFN-γ) and interleukin (IL)-4 secretion of supernatant of cultured CD4 ⁺ and CD8 ⁺ T cells were measured by enzyme-linked immunosorbent assays (ELISA). For adoptive transfer, recipient mice were injected with MOG_35–55-specific CD8⁺ or CD4⁺ T cells. EAE clinical course was measured by EAE score at 0–5 scale and spinal cord was examined by staining with hematoxylin and eosin and Luxol fast blue staining.

CD8⁺CD3⁺ and CD4⁺CD3 ⁺ cells were 86% and 94% pure of total CD3⁺ cells after CD8/CD4 bead enrichment, respectively. These cells were stimulated by MOG_35–55 peptide and applied to proliferation assays. Although the CD8⁺ T cells had a generally lower response to MOG_35–55 than CD4⁺ T cells, the response of CD8⁺ T cells was not always dependent on CD4. CD8⁺ T cell secreted less IFN-γ and IL-4 compared with CD4⁺ T cells. EAE was induced in wildtype B6 naïve mice by adoptive transfer of MOG_35–55-specific T cells from B6 active-induced EAE (aEAE) mice. A similar EAE score and slight inflammation and demyelination were found in naive B6 mice after transferring of CD8 ⁺ T cells from immunized B6 mice compared with transfer of CD4 ⁺ T cells.

Our data suggest that CD8⁺ autoreactive T cells in EAE have a lower encephalitogenic function but are unique and independent on pathogenic of EAE rather than their CD4⁺ counterparts.

X-linked inhibitor of apoptosis (XIAP) is a vital factor in the anti-apoptosis mechanism of tumors and is highly expressed in renal cell carcinoma (RCC). However, the mechanism through which XIAP regulates DNA damage repair is unknown. This study investigated the regulatory mechanism of XIAP in etoposide-induced apoptosis in two Caki-1 cell lines with high or low XIAP expression.

The two cell lines were established using RNA interference technology. The differentially expressed proteins in the two cell lines were globally analyzed through an isobaric tags for relative and absolute quantitation-based quantitative proteomics approach. Proteomic analysis revealed 255, 375, 362, and 5 differentially expressed proteins after 0, 0.5, 3, and 12 h of drug stimulation, respectively, between the two cell lines. The identified differentially expressed proteins were involved in numerous biological processes. In addition, the expression of histone proteins (H1.4, H2AX, H3.1, H3.2, and H3.3) was drastically altered, and the effects of XIAP silencing were accompanied by the marked downregulation of H2AX. Protein-protein interactions were assessed and confirmed through immunofluorescence and Western blot analyses.

The results suggested that XIAP may act as a vital cell signal regulator that regulates the expression of DNA repair-related proteins, such as H2AX, and influences the DNA repair process.

Given these functions, XIAP may be the decisive factor in determining the sensitivity of RCC cell apoptosis induction in response to chemotherapeutic agents.

Tuberculosis (TB) is one of the most debilitating diseases worldwide. Current studies have shown that vitamin D plays a significant role in host immune defense against Mycobacterium tuberculosis, but clinical trials reported inconsistent results. Therefore, we systematically reviewed the literature to investigate whether vitamin D supplementation could improve the effect of anti-TB therapy.

We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from their inception to February 8th, 2019 for randomized controlled trials on vitamin D supplementation in patients with pulmonary TB receiving anti-TB therapy. The primary outcomes were time to sputum culture and smear conversion and proportion of participants with negative sputum culture. The secondary outcomes were clinical response to treatment and adverse events. A random-effects model was used to pool studies. Data were analyzed using RevMan 5.3 software.

Five studies with a total of 1126 participants were included in our meta-analysis. Vitamin D supplementation did not shorten the time to sputum culture and smear conversion (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.89–1.23, P = 0.60; HR 1.15, 95% CI 0.93–1.41, P = 0.20, respectively) and did not lead to an increase in the proportion of participants with negative sputum culture (relative risk [RR] 1.04, 95% CI 0.97–1.11, P = 0.32). However, it reduced the time to sputum culture conversion in the sub-group of participants with TaqI tt genotype (HR 8.09, 95% CI 1.39–47.09, P = 0.02) and improved the multidrug-resistant(MDR) TB sputum culture conversion rate (RR 2.40, 95% CI 1.11–5.18, P = 0.03). There was no influence on secondary outcomes.

Vitamin D supplementation had no beneficial effect on anti-TB treatment, but it reduced the time to sputum culture conversion in participants with tt genotype of the TaqI vitamin D receptor gene polymorphism and improved the MDR TB sputum culture conversion rate.

The clinical outcome of transtrochanteric rotational osteotomy (TRO) for osteonecrosis of the femoral head (ONFH) remains controversial, and the promising clinical results of several Japanese studies could not be reproduced in American and European studies. Trying to solve controversies on TRO for ONFH rising from apparently conflicting studies, a meta-analysis was conducted to assess the 5- and 10-year hip survival rates (with conversion to artificial joint replacement and radiographic failure as endpoints) after TRO.

All eligible studies were searched in seven comprehensive databases including PubMed, Web of Science, Embase, Cochrane Library, VIP Database, China Knowledge Resource Integrated Database, and Wan Fang Database prior to June 2019. The outcomes evaluated were 5- and 10-year hip survival rates after TRO. The odds ratio and risk difference for the noncomparative binary data with the 95% confidence intervals (CIs) were calculated for each outcome. The included studies were assessed for methodologic bias and potential reasons for heterogeneity were explored.

Nineteen studies of TRO for ONFH were eligible for this meta-analysis according to inclusion criteria. Based on the previous report, two calculation methods (Methods 1 and 2) were adopted in this meta-analysis. Furthermore, we performed a subgroup analysis of the 5- and 10-year hip survival rates (Method 1) after TRO for ONFH: Asian sub-population and non-Asian subpopulation. Taking conversion to artificial joint replacement as the endpoint, 5- and 10-year hip survival rates (Method 1) after TRO for ONFH in the Asian population were 0.86 (95% CI = 0.82–0.89) and 0.72 (95% CI = 0.65–0.78), respectively, and 5- and 10- year hip survival rates after TRO for ONFH in the non-Asian population were 0.55 (95% CI= 0.43–0.67) and 0.42 (95% CI = 0.28–0.55), respectively. The 5- and 10-year hip survival rates (Method 2) after TRO for ONFH were 0.90 (95% CI = 0.79–0.95) and 0.89 (95% CI = 0.81–0.94), respectively. Taking radiographic failure as the endpoint, 5- and 10-year hip survival rates after TRO for ONFH were 0.70 (95% CI= 0.64–0.76) and 0.53 (95% CI= 0.46–0.61), respectively.

The 5- and 10-year hip survival rates after TRO for ONFH were satisfactory in the Asian population, and were acceptable in the non-Asian population despite high early failure rates.

To review the latest progress on the pathogenic mechanism and management of rheumatoid arthritis (RA)-associated coronary artery disease (CAD), and propose advice on future management optimization as well as prospects for research and development of new therapeutic regimen.

This study was based on data obtained from PubMed up to May 2019 using various search terms and their combinations, including coronary artery disease, myocardial ischemia, cardiovascular diseases, RA, rheumatic diseases, treatment, therapy, strategies, immunotherapy, inflammation, and anti-inflammation.

All retrieved literature was scrutinized, most relevant articles about the pathogenic mechanism and clinical management, especially anti-inflammatory therapy of RA-associated CAD were reviewed.

RA is an immune-mediated chronic inflammatory disease which has a great social disease burden. In addition to typical arthritic manifestations, RA also affects extra-articular tissues and organs, within which the involvement of the cardiovascular system, especially incorporating CAD, is the leading cause of death for patients with RA. Recently, numerous basic and clinical studies have been carried out on the mechanism of CAD development and progression under the inflammatory cascade of RA. The effect of traditional RA drugs on CAD risk management has been gradually clarified, and more emerging biologic agents are being explored and studied, which have also achieved satisfactory outcomes. Furthermore, with the success of the CANTOS clinical trial, novel anti-inflammatory therapy for the prevention of cardiovascular disease is believed to have a broad prospect.

RA is an independent risk factor for CAD, which mainly results from the underlying inflammatory cascade; therefore, anti-inflammatory therapy, especially the emerging novel biologic drugs, is important for CAD management in patients with RA and may also be a promising approach among the general population.

Endometriosis is a common gynecologic disease that frequently leading to chronic pelvic pain, severe dysmenorrhea, and subfertility. As first-line hormonal treatment can interfere with ovulation and may cause recurrent pelvic pain, exploration of new non-hormonal therapeutic approaches becomes increasingly necessary. This review aimed to evaluate the pre-clinical and clinical efficacy and safety of non-hormonal treatment for endometriosis

Databases including PubMed, Embase, Cochrane Library, SINOMED, ClinicalTrials.gov, and Google Scholar were searched up to October 2019, using search terms "endometriosis" and "non-hormonal therapy."

Twenty-four articles were reviewed for analysis, including nine animal studies and 15 human trials; all were published in English.

Twenty-four articles were identified, including 15 human trials with 861 patients and nine animal studies. Some agents have been evaluated clinically with significant efficacy in endometriosis-related pelvic pain and subfertility, such as rofecoxib, etanercept, pentoxifylline, N-palmitoylethanolamine, resveratrol, everolimus, cabergoline (Cb2), and simvastatin. Other drugs with similar pharmacological properties, like parecoxib, celecoxib, endostatin, rapamycin, quinagolide, and atorvastatin, have only been tested in animal studies.

Clinical data about most of the non-hormonal agents are not sufficient to support them as options for replacement therapy for endometriosis. In spite of this, a few drugs like pentoxifylline showed strong potential for real clinical application.

恶性骨盆骨肿瘤的切除对骨科肿瘤学家提出了主要的技术挑战，因为肿瘤尺寸大，在早发性和局部复杂解剖结构中无法检测到，并且严重延伸到主要神经血管结构以及肠道和泌尿道。^[1]传统上，恶性骨盆骨肿瘤通过后躯截肢切除，该手术明显影响有害的美容和身体结果。已经进行了更多的尝试来进行保肢和改善肿瘤切除术后骨盆的重建。然而，由于骨盆骨肿瘤发病率低，单一肿瘤中心无法积累丰富的临床经验。此外，由于解剖结构的复杂性和缺乏临床经验，肿瘤患者以前预后不良。近二十年来，随着外科技术和相关学科的发展，我国许多医院，尤其是北京大学人民医院肌肉骨骼肿瘤中心，积累了大量的骨盆恶性肿瘤手术经验。近年来，我国骨科肿瘤专家的疗效显著，使患者的总生存率、保肢率和下肢功能明显改善。本文对近20年来盆腔恶性肿瘤保肢手术进行综述。

踝关节炎是一种以关节软骨退变为特征的疾病，常伴有疼痛、活动能力下降和内翻畸形。

致编辑：Cronkhite-Canada综合征（CCS）是一种罕见的非遗传性疾病，以弥漫性胃肠道息肉病和外胚层异常为特征。^[1]尽管CCS息肉不被认为是肿瘤性的，但15%至25%的患者在诊断时被记录为结肠直肠癌或胃癌，高达40%的患者被记录为腺瘤和腺瘤性变化。^[2]胃肠外肿瘤已有零星报道，但其与CCS的关系仍在研究中。CCS的潜在机制研究较少，只有一项全外显子组测序（WES）研究确定了可能有助于发病机制的蛋白激酶DNA激活催化亚基（PRKDC）DNA变体。^[3]在此，我们报告一例合并三种恶性肿瘤的CCS病例。对该病例的WES分析确定了某些种系突变，这些突变可能有助于深入了解发病机制。本研究由中国医学科学院北京协和医院伦理委员会批准（编号：ZS-1725）。

致编辑：梭形细胞癌（SpCC）是一种罕见的组织学类型的肉瘤样癌，由梭形肿瘤细胞组成。SpCC可以发生在许多不同的器官，包括肺。关于肺SpCC的临床表现、基因突变表型、治疗和预后的数据有限。分子靶向治疗对该肿瘤的疗效仍不清楚。^[1]在这里，我们报告了一例携带原肌球蛋白3-ROS原癌基因1的转移性SpCC成年男性（TPM3-ROS1)对酪氨酸激酶抑制剂（TKI）克唑替尼靶向治疗表现出长期反应的融合患者。

致编辑：一名66岁男性主诉腹痛和腹胀1个月，入住中国北京宣武医院普外科。患者体温正常，无恶心、腹泻、骨/关节痛等症状。他没有过敏史，没有特殊的既往病史或家族史。他没有服用可能导致嗜酸性粒细胞增多的药物。粪便中未发现寄生虫。腹部计算机断层扫描（CT）显示胃壁增厚和蠕动僵硬，周围淋巴结肿胀，表明胃癌的可能性[图1A].胃镜活检显示胃壁大量嗜酸性粒细胞浸润[图1B].同时，血液检查显示白细胞（WBC）计数升高至11.09 × 10⁹/L，嗜酸性粒细胞升高至2.53 × 10⁹/L，血红蛋白160 g/L，血小板269 × 10⁹/L。骨髓活检显示细胞结构正常，嗜酸性粒细胞增加。未检测到断点簇区/c-abl癌基因1、非受体酪氨酸激酶和Fip1-like1以及血小板衍生生长因子受体α融合基因。他被诊断为嗜酸性粒细胞增多综合征（HES），并接受皮质类固醇治疗（泼尼松20 mg，口服，每日两次）。患者腹痛、腹胀症状逐渐减轻，2周时嗜酸性粒细胞总数恢复正常。治疗后3个月和6个月随访胃镜显示胃壁正常[图1C和图1D].皮质类固醇逐渐减少，并在治疗8个月后停用。

致编辑：胰腺癌是全球癌症死亡的主要原因之一。提示诊断的显著症状往往在肿瘤侵犯周围组织或转移时出现，导致诊断较晚，完全切除不可行。对于晚期患者，缺乏有效的全身治疗药物进一步限制了他们的生存时间。Olaparib是一种聚（ADP-核糖）聚合酶（PARP）抑制剂（PARPi），具有几种已记录的作用机制，包括抑制碱基切除修复以及捕获PARP。^[1]这些机制抑制单链断裂(SSB)的修复，因此导致双链断裂(DSB)的诱导。同源重组-DNA损伤修复（HRDDR）严重缺陷的肿瘤对DSB的修复无效，DSB理论上对PARPi治疗敏感。干旱1A，大型ATP依赖性染色质重塑复合物的一部分SNF/SWI通常被染色质抑制的基因的转录激活所必需的。截短突变和拷贝数丢失都可能导致功能缺失干旱1A蛋白质，导致与对PARPi的反应相关的HR-DRR缺乏。临床前研究显示干旱1A可能使癌细胞对PARPi敏感。^[2]然而，迄今为止尚未发表胰腺导管腺癌（PDAC）的相关试验或病例报告。在这里，我们提出了一个PDAC患者的报告与有害干旱1A突变（p.Q1327*），对基于奥拉帕尼的治疗保持应答超过13.0个月。

致编辑：一名37岁中国女性，不吸烟，表现为左肺腺癌（IV期）[图1A]、恶性胸腔积液和多发性骨转移。肿瘤活检的脱氧核糖核酸测序显示表皮生长因子受体（EGFR）外显子19缺失，因此于2014年12月开始吉非替尼治疗。除1级皮疹外，无治疗相关副作用，病情稳定。不幸的是，该患者没有经历长期获益，仅在两个月后就出现了疾病进展。随访检查显示，颅外疾病和颅内小病灶已逐渐发展。2015年4月，患者接受了全脑放疗（30 Gy，分10次）和4个周期的培美曲塞单药治疗。病情稳定，同时患者咳嗽、气短和一般状况有所改善。化疗疗程改为培美曲塞联合顺铂两个周期。达到部分缓解（PR），患者接受14个周期的培美曲塞单药维持化疗。随访评估显示患者病情稳定；然而，患者的疾病在23个月后进展。2017年3月的计算机断层扫描（CT）显示肺部病变和恶性胸腔积液的大小都增加了[图1B].随后的活检标本进行下一代测序(NGS)和多配体聚糖4-c-ros癌基因1（SDC4-ROS1)检测到重排[图1C].患者随后于2017年4月接受克唑替尼治疗，并获得PR[图1D].2018年8月进行的CT扫描显示左肺原发病灶进展和恶性胸腔积液。然而，其余病变的生长保持稳定。

致编辑：遗传性血色病（HH）是一种迟发性自主神经疾病，以肠道对铁的吸收增强和铁超载为特征，可导致肝硬化、心肌病、糖尿病、关节炎和皮肤色素沉着。1996年，Feder等人^[1]克隆了负责HH的基因（HFE）并报道85%的HH患者是纯合子C282Y突变HFE基因。这随后被称为1型HH。存在其他遗传形式的HHHFE-相关的，其实例是青少年血色病(JH)；迄今为止，已经报道了两种诱导JH的基因型。一种JH基因型涉及血幼素基因（HJV），它是由Papanikolaou从一个患有JH的希腊家庭克隆的等人^[2]并且被称为2A型HH。另一种涉及人抗菌肽（汉普)基因，其编码铁调素并被称为2B型HH。

致编辑：冠心病（CHD）和抑郁症在世界范围内的患者中很常见，并且具有很高的共病率。对抑郁症的研究表明，抑郁症与冠心病的长期风险有关。^[1]抑郁症合并冠心病的发病率和死亡率较高，预后较差。^[2]冠心病和抑郁症之间的联系已经得到很好的证实，并且被认为是双向的。^[3]因此，为今后抑郁症合并CHD的研究提供可能的条件，建立可靠的抑郁症合并CHD的动物模型是必要的。慢性不可预测轻度应激（CUMS）是过去几年中最广泛用于建立抑郁症动物模型的。给大鼠喂食高脂肪饮食（HFD）是建立动脉粥样硬化和CHD模型的广泛使用的方法。研究报道，被关在单个笼子里并食用致动脉粥样硬化饮食的雌性食蟹猴可以发展出抑郁症合并CHD模型。^[4]另有论文报道大鼠CUMS合并HFD与人类血管性抑郁症的临床表现相似。^[5]前者证明了在猴子中饲养在单个笼子中并喂养致动脉粥样硬化饮食可以建立抑郁症合并CHD模型，后者证明了大鼠CUMS合并HFD类似于血管性抑郁症。目前尚不清楚大鼠CUMS联合HFD是否可以建立一个复杂的抑郁症伴冠心病的大鼠模型。因此，本研究的目的是探索大鼠CUMS联合HFD是否可以建立一个有代表性、可靠的抑郁症伴CHD的大鼠模型，并为深入研究抑郁症伴CHD提供可能的条件。

致编辑：在2018年10月版发表的一篇论文中，Balkac和Ergun概述了信息图表在医疗保健中的发展作用。^[1]他们指出，Smiciklas将信息图定义为数据可视化，试图以易于理解的方式向受众传达复杂的信息。^[2]