Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. In our previous study, we surveyed both IgG and IgM-bound serological biomarkers and validated a panel of IgG-bound autoantigens for early LC diagnosis with 50% sensitivity at 90% specificity. To further improve the performance of these serological biomarkers, we surveyed HuProt arrays, comprised of 20,240 human proteins, for IgA-bound autoantigens because IgAs are a major immunoglobulin isotype in the lung. Integrating with IgG-bound autoantigens, we discovered and validated a combined biomarker panel using ELISA-format tests. Specifically, in Phase I, we obtained IgA-based autoimmune profiles of 69 early stage LC patients, 30 healthy subjects and 25 patients with lung benign lesions (LBL) on HuProt arrays and identified 28 proteins as candidate autoantigens that were significantly associated with early stage LC. In Phase II, we re-purified the autoantigens and converted them into an ELISA-format testing to profile an additional large cohort, comprised of 136 early stage LC patients, 58 healthy individuals, and 29 LBL patients. Integration of IgG autoimmune profiles allowed us to identify and validate a biomarker panel of three IgA autoantigens (
Objective: To summarize the clinical diagnosis and therapeutic method in chronic hepatitis B (CHB) combined with autoimmune hepatitis (AIH). Methods: Clinical manifestations, laboratory examination, imaging, histopathological characteristics, treatment and prognosis of 19 cases diagnosed with CHB combined with AIH followed at the outpatient Department of Gastroenterology of Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine during December 2013 to June 2018 were retrospectively analyzed. Paired sample t-test was used before and after treatment for the measurement of normal distribution data. Measurement data of non-normal distribution were expressed as a median (quartile spacing) and Wilcoxon matched-pairs signed rank test was used before and after treatment. Results: Among the 19 cases, 5 were male and 14 were female. The age of onset was 35 to 63 years, and the average age was 47.10 ± 8.76 years. There were 12 cases diagnosed with CHB before AIH, 5 cases diagnosed with AIH before CHB, and 2 cases diagnosed with AIH and CHB at the same time. After the definite diagnosis of CHB combined with AIH, nucleoside (acid) analogues (antiviral against hepatitis B virus) combined glucocorticoid therapy were given, and azathioprine or mycophenolate mofetil (immunosuppressant) was added according to the intrahepatic inflammation (inflammation graded at G3 and above) and leukocyte conditions. The duration of treatment varied between 2 weeks to 16 (median treatment duration of 6 weeks), except for one case who was just diagnosed and followed up. Biochemical indicators and immunoglobulin of the remaining 18 cases before and after treatment was significantly decreased, and the differences were statistically significant (P < 0.05), with HBV DNA < 20 copies/ml. Conclusion: CHB combined with AIH diagnosis can be easily missed. Therefore, it requires comprehensive diagnosis combined with clinical characteristics, autoantibodies, and immunoglobulin levels with special emphasis on pathological characteristics of liver tissue. Anti-HBc-positive patients using immunosuppressant should be carefully monitored for HBV DNA and anti-HBV treatment should be given if necessary.目的： 总结慢性乙型肝炎（CHB）合并自身免疫性肝炎（AIH）的临床诊断和治疗方法。 方法： 回顾性分析2013年12月至2018年6月上海交通大学医学院附属仁济医院消化内科门诊随访的19例诊断为CHB合并AIH患者的临床表现、实验室检查、影像学、病理组织学特点、治疗及转归情况，正态分布计量资料治疗前后比较采用配对样本t检验；不符合正态分布的计量资料以中位数（四分位数间距）表示，治疗前后比较采用配对样本的Wilcoxon符号秩和检验。 结果： 19例患者中男性5例、女性14例，发病年龄35～63（47.10±8.76）岁。CHB先于AIH诊断有12例，AIH先于CHB诊断有5例，AIH和CHB同时诊断有2例。明确诊断CHB合并AIH后，予以核苷（酸）类似物抗乙型肝炎病毒联合糖皮质激素治疗，并根据肝内炎症（炎症分级在G3及以上）及白细胞情况加用免疫抑制剂硫唑嘌呤或吗替麦考酚酯。治疗2周至16周不等（治疗中位时间6周），除1例刚诊断治疗随访中外，其余18例患者治疗前后生物化学指标、免疫球蛋白均明显下降，治疗前后指标差异均有统计学意义（P值均< 0.05），HBV DNA均< 20拷贝/ml。 结论： CHB合并AIH容易漏诊，需要结合临床特点、自身抗体、免疫球蛋白水平，尤其重视肝组织病理学特点进行综合诊断。对抗-HBc阳性使用免疫抑制剂治疗的患者，应加强对HBV DNA的监测，必要时需抗乙型肝炎病毒治疗。.
Circulating microRNAs (miRNAs) have shown the potential for non-invasive diagnosis of various types of malignancies at an early stage. The aim of the study was to explore the feasibility of a combination of 8 serum miRNAs related to non-small-cell lung cancer (NSCLC) with the corresponding serum exosomal miRNAs in early diagnosis for the patients with NSCLC.We measured 8 serum miRNAs and the corresponding serum exosomal miRNAs including miR-21-5p, miR-126-3p, miR-141-3p, miR-146a-5p, miR-155-5p, miR-222-3p, miR-223-3p, and miR-486-5p in 48 patients with early NSCLC at stages I/II, 32 patients with lung benign lesion (LBL), and 48 healthy control (HC) by quantitative real-time polymerase chain reaction (qRT-PCR).The expression levels of 4 serum miRNAs including miR-21-5p, miR-141-3p, miR-222-3p, and miR-486-5p, and 2 serum exosomal miRNAs including miR-146a-5p and miR-486-5p in the early NSCLC group were significantly different from that in the LBL group and the HC group (P < 0.01). The areas under the receiver operating characteristic curves (AUC) of the 4 serum miRNAs and 2 serum exosomal miRNAs in the early NSCLC group were ≥0.697, of which serum exosomal miR-146a-5p and miR-486-5p were 0.813 and 0.886, respectively, and higher than that of the 4 serum miRNAs. Additionally, a combination of 4 serum miRNAs with 2 serum exosomal miRNAs improved the AUC to 0.960 for the patients with NSCLC at early stages, with a sensitivity of 85.42% and a specificity of 92.50%.This study suggests that serum exosomal miRNAs other than serum miRNAs might be preferable biomarkers for the patients with NSCLC at early stages, and a combination of serum miRNAs with serum exosomal miRNAs contributes to the further improvement of early diagnosis for NSCLC.
Objective:The aberrant expression of tumor-associated antigens (TAAs) is responsible for the release of large amounts of autoantibodies in sera, and serum autoantibody detection has been demonstrated to contribute to the early diagnosis of malignancies.Recent studies showed the closely correlation of transcriptional intermediary factor-1γ (TIF1γ) with some malignancies.In our pilot study, we found aberrantly high expression of TIF1γ protein existed in cancer tissues other than matched paracancerous tissues of patients with lung cancer (LC) at early stage by immunohistochemistry (IHC) staining.As a result, this study aims to detect the expression of autoantibodies against TIF1γ in sera of patients with LC at early stage by using enzyme-linked immunosorbent assay (ELISA) and investigate its potential value for the early diagnosis of LC.Methods: The expressions of TIF1γ protein in 60 pairs of LC tissues and matched paracancerous tissues were detected by IHC staining.The levels of anti-TIF1γ-IgA, IgG, IgM, and IgE in the sera of 248 patients with LC at early stage, 200 patients with lung benign lesions (LBL), and 218 healthy controls (HC) were detected by ELISA, respectively.Western blot was used to validate the ELISA results of serum autoantibodies against TIF1γ.Results: The positive rate of TIF1γ protein expression in LC tissues was 83.33%, which was significantly higher than 25.00% in paracancerous tissues (P<0.01).The levels and positive rates of serum anti-TIF1γ-IgM and anti-TIF1γ-IgE in early LC group had no significant difference from that in LBL group and HC group (P>0.05),while the levels and positive rates of anti-TIF1γ-IgA and anti-TIF1γ-IgG were significantly higher than that in LBL group and HC group (P<0.01), of which anti-TIF1γ-IgA showed the area under the receiver operating characteristic curve (AUC) of 0.704 for the patients with LC at early stage, with 28.20% sensitivity at 95.93% specificity, and anti-TIF1γ-IgG showed the AUC of 0.622 for the patients with LC at early stage, with 18.54% sensitivity at 94.25% specificity.The results of anti-TIF1γ-IgA and anti-TIF1γ-IgG in western blot were consistent with that in ELISA.Additionally, the combination of anti-TIF1γ-IgA and anti-TIF1γ-IgG improved the AUC to 0.734, with 38.31% sensitivity at 92.34% specificity. Conclusions:There is a strong humoral immune response to autologous TIF1γ existing in patients with early LC.Both serum anti-TIF1γ-IgA and anti-TIF1γ-IgG show the diagnostic value for the patients with LC at early stage, of which anti-TIF1γ-IgA is donstrated to be a preferable biomarker, and the combined detection of anti-TIF1γ-IgA and anti-TIF1γ-IgG might contribute to the further improvement of early diagnosis for LC.
Background and Aims: The COVID-19 pandemic poses a great challenge to healthcare. We aimed to investigate the impact of COVID-19 on the healthcare of patients with inflammatory bowel disease (IBD) in epicenter and non-epicenter areas. Methods: Patients with IBD from Hubei province (the epicenter of COVID-19) and Guangdong province (a non-epicenter area), China were surveyed during the pandemic. The questionnaire included change of medications (steroids, immunomodulators, and biologics), procedures (lab tests, endoscopy, and elective surgery), and healthcare mode (standard healthcare vs. telemedicine) during 1 month before and after the outbreak of COVID-19. Results: In total, 324 IBD patients from Guangdong province (non-epicenter) and 149 from Hubei province (epicenter) completed the questionnaire with comparable demographic characteristics. Compared to patients in Guangdong province (non-epicenter), significantly more patients in Hubei (epicenter) had delayed lab tests/endoscopy procedures [61.1% (91/149) vs. 25.3% (82/324), p < 0.001], drug withdrawal [28.6% (43/149) vs. 9.3% (30/324), p < 0.001], delayed biologics infusions [60.4% (90/149) vs. 19.1% (62/324), p < 0.001], and postponed elective surgery [16.1% (24/149) vs. 3.7% (12/324), p < 0.001]. There was an increased use of telemedicine after the outbreak compared to before the outbreak in Hubei province [38.9% (58/149) vs. 15.4% (23/149), p < 0.001], while such a significant increase was not observed in Guangdong province [21.9% (71/324) vs. 18.8% (61/324), p = 0.38]. Approximately two-thirds of IBD patients from both sites agreed that telemedicine should be increasingly used in future medical care. Conclusions: Our patient-based survey study in a real-world setting showed that COVID-19 resulted in a great impact on the healthcare of patients with IBD, and such an impact was more obvious in the epicenter compared to the non-epicenter area of COVID-19. Telemedicine offers a good solution to counteract the challenges in an unprecedented situation such as COVID-19.
Thalidomide is effective in inducing and maintaining clinical remission, as well as mucosal healing, in patients with refractory Crohn's disease (CD). However, long-term use of thalidomide has raised concern because of the high incidence of adverse events. Cardiovascular events induced by thalidomide have been reported in patients with multiple myeloma, amyotrophic lateral sclerosis, and transfusion-dependent refractory anemia. We report here an extremely rare case of sinus bradycardia induced by thalidomide in an adult patient with CD. This patient's heart rate converted back to a normal sinus rhythm after withdrawal of thalidomide, but recurred after restarting of thalidomide. Cardiac toxicity should be closely monitored when using thalidomide in patients with CD.
Abstract This article provides an overview of the major pathologic manifestations of Meckel-Gruber syndrome, current knowledge about its pathogenesis, minimal diagnostic criteria, and differential diagnosis. Typical sonographic findings (occipital encephalocele, postaxial polydactyly, and cystic enlargement of the kidneys) allow for diagnosis of most cases before the 14th week of gestation, but the pathologist may encounter clinically unsuspected or atypical cases that require morphologic confirmation. In these cases, a meticulous autopsy is necessary to establish the diagnosis of Meckel-Gruber syndrome.
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