tbuckley/cabot-search huggingface dataset:
Validation of secreted protein OASEP1 as a prognostic biomarker and therapeutic target for oral cancer.
Authors: Atsushi Takano, Yoshihiro Yoshitake, Masanori Shinohara, Yataro Daigo
Journal: Journal of Clinical Oncology (2020)

e18520 Background: Although current treatments for oral cancer (OC) include surgery, radiotherapy, and chemotherapy, their effectiveness is still limited. Therefore, the development of novel prognostic biomarkers and/or therapeutic agents is urgently needed. Methods: Our strategies are as follows: i) Identification of up-regulated genes in cancers by means of gene expression microarray, ii) Validation of clinicopathological significance of their protein expression by tissue microarray, iii) Examination of their growth effect on cancer cells by siRNAs and active ligand protein for growth assays. Results: We selected a secreted protein, OASEP1 (OC-associated serum protein 1) as a candidate. Real-Time qPCR and Western blotting showed that OASEP1 gene and its gene product were expressed in the majority of OC cells. Immunohistochemical staining showed that OASEP1 expression was observed in 73 (74.4%) of 98 OCs that had undergone curative surgery. In addition, high level of OASEP1 expression was associated with poor prognosis for OC patients ( P = 0.0158, by log-rank test). Suppression of OASEP1 expression by siRNAs for OASEP1 (si-OASEP1) significantly suppressed the growth and invasion of OC cell lines. Flowcytometry and live cell imaging showed that si-OASEP1 induced the apoptosis of OC cells. siRNAs against OASEP1-receptor also suppressed the growth of OC cells. Addition of active OASEP1 recombinant protein into culture media enhanced the growth of OC cells probably through AKT pathway. Our data suggest that OASEP1 and its receptor could play a significant role in the growth of OC cells in probable autocrine/paracrine manner. Conclusions: OASEP1 is a possible prognostic biomarker and therapeutic target for OC.
Clinical analysis of adrenal ganglioneuroma: a report of 21 cases
Authors: Jiang Li, Chang-hai Yang, Li-ming Li
Journal: BMJ (2010)

The clinical data of 21 cases of adrenal ganglioneuroma treated in our hospital from July 1988 to August 2008 were reviewed. The clinical manifestations were: lower back uncomfortableness (9 cases), paroxysmal dizziness (4 cases), central obesity ( 1 case) and 7 cases were discovered incidentally.Five cases were diagnosed pre-operationally and remaining 16 cases were diagnosed post-operationally by pathology. All patients completely recovered after surgery except one, who still had dizziness with high blood pressure. Ultrasonography, CT and MRI examinations are the main diagnostic methods for adrenal ganglioneuroma, and it is confirmed by histopathology, surgical removal of the tumor is the main therapy for the disease.

Key words: 
Adrenal gland neoplasms;  Ganglioneuroma
Guidelines on the use of liver biopsy in clinical practice from the British Society of Gastroenterology, the Royal College of Radiologists and the Royal College of Pathology
Authors: James Neuberger, Jai Patel, Helen Caldwell, Susan Davies, Vanessa Hebditch, Coral Hollywood, Stefan Hubscher, Salil Karkhanis, Will Lester, Nicholas Roslund, Rebecca West, Judith I Wyatt, Mathis Heydtmann
Journal: Gut (2020)

Liver biopsy is required when clinically important information about the diagnosis, prognosis or management of a patient cannot be obtained by safer means, or for research purposes. There are several approaches to liver biopsy but predominantly percutaneous or transvenous approaches are used. A wide choice of needles is available and the approach and type of needle used will depend on the clinical state of the patient and local expertise but, for non-lesional biopsies, a 16-gauge needle is recommended. Many patients with liver disease will have abnormal laboratory coagulation tests or receive anticoagulation or antiplatelet medication. A greater understanding of the changes in haemostasis in liver disease allows for a more rational, evidence-based approach to peri-biopsy management. Overall, liver biopsy is safe but there is a small morbidity and a very small mortality so patients must be fully counselled. The specimen must be of sufficient size for histopathological interpretation. Communication with the histopathologist, with access to relevant clinical information and the results of other investigations, is essential for the generation of a clinically useful report.
纳络酮治疗肺性脑病34例
Authors: 姚德胜, 张秋现
Journal: BMJ (2005)

将66例肺性脑病患者随机分为两组.试验组(34例)在常规治疗的基础上,给予纳络酮0.8 mg静脉注射后,以纳络酮 2.0 mg每日1次静脉滴注;对照组(32例)给予尼可刹米、洛贝林联合静脉滴注.试验组在48 h治疗过程中清醒率明显高于对照组;治疗48 h后治疗组动脉血二氧化碳分压明显低于对照组(P＜0.05),动脉血氧分压明显高于对照组(P＜0.01).表明纳络酮能有效促进肺性脑病患者苏醒并有效改善患者的通气功能。
Assessment of coronary atherosclerotic plaques in type 2 diabetic patients
Authors: Xue-yu Zhong, Jing Li
Journal: BMJ (2010)

The study intended to evaluate the atherosclerotic plaque burden and composition among symptomatic patients with and without type 2 diabetes mellitus.Total 262 symptomatic patients, including 79 with type 2 diabetes and 183 without, underwent multislice computed tomography coronary angiography.The extent of coronary atherosclerosis and 3 plaque types were studied.Patients with diabetes showed more diseased coronary segments ( P ＜ 0.01 ) and more nonobstructive segments ( P ＜ 0.05 ) than non diabetic patients.Compared to non diabetic patients,diabetic patients had a higher number of coronary segments with non-calcified ( P = 0.005 ) and calcified ( P = 0.016 ) plaques, but not for mixed plaques.The results indicate that type 2 diabetic patients have higher coronary plaque burden.

Key words: 
Diabetes mellitus, type 2;  Coronary atherosclerosis
The mutation frequency of HPD related genes in different lung cancer stages.
Authors: Yanhui Wan, Fuyuan Fang, Guodong Wu, Xing Zhang, Chao Song, Minqi Tian, Jiyu Tang
Journal: Journal of Clinical Oncology (2020)

e21006 Background: Clinical detections of hyper-progressive disease (HPD) gene mutations in advanced lung cancer should be considered to avoid the inappropriate immunotherapy, and recently neoadjuvnat and adjuvant immunotherapy also proved to be efficacy in early stage of lung cancer. Nevertheless, it still remains poorly understanding of the distribution of HPD related mutations in early stage lung cancer. Methods: In this study, according to information of patient specimens from public database TCGA, Ⅰ and Ⅱ stages were defined as early stage, Ⅲ and Ⅳ stages were defined as advanced stage. The mutations in HPD related genes were evaluated including CNVs of CCND1, FGF19, FGF3, FGF4, MDM2 and MDM4, and SNVs of DNMT3A. Chi-square test was performed to analyze the differences of HPD related gene mutation frequency in early and advanced stages. Results: Based on the statistics of clinical data from TCGA, we found 399 early stage cases and 110 advanced stage cases in patients with lung adenocarcinoma (LUAD), 402 early stage cases and 91 advanced stage cases in patients with lung squamous cell carcinoma (LUSC). In early stage, we found 76, 76, 76, 75, 89, 201 cases of CNVs of CCND1, FGF19, FGF3, FGF4, MDM2 and MDM4, 10 cases of SNVs of DNMT3A, respectively. In advanced stage, we counted 32, 32, 32, 29, 21, 37 cases of CNVs of CCND1, FGF19, FGF3, FGF4, MDM2 and MDM4, 4 cases of SNVs of DNMT3A, respectively. No significant differences of mutation frequency HPD related gene between early and advanced stages were found via χ 2 test. CNVs frequencies of CCND1, FGF19, FGF3, FGF4 and MDM4 in LUAD were significantly lower than them in LUSC. No significant differences of CNVs frequency of MDM2 and SNVs frequency of DNMT3A beween patients with LUAD and patients with LUSC were found. Conclusions: Our analysis indicated that immunotherapy for patients with early stage lung cancer also needed to test these mutations. LUSC patients required paying more attentions on HPD related mutations of which frequencies were significantly higher than LUAD patients. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.
Characteristics of patients visiting emergency department by different ways of transportation
Authors: Dong Luo, Tao Cheng, Mingming Dong, Fang Shen, Guihua Yang, Yu Cao, Rong Yao
Journal: BMJ (2019)

Objective
To explore the characteristics of patients visiting emergency department by different ways of transportation.


Methods
The medical information of 23 039 patients visiting emergency department from January 2017 to December 2017 was obtained through the Hospital Information System (HIS). There were 20 856 patients visiting emergency arranged by themselves (self-visiting group), and 2 183 patients sent by ambulance (ambulance group). The characteristics of two groups were compared.


Results
The proportion of young patients in the self-visit group was the highest (45.97%, 9 587/20 856), and the proportion of elderly patients in the ambulance group was the highest (40.04%, 874/2 183). Throughout the year, the number of patients who came to the hospital by themselves was the highest in the summer, that by ambulance was the highest in the winter, while that was the lowest in spring for both groups. There was no significant fluctuation in the number of patients who came to the hospital during the week. In the self-visited group, the daily peak hours were 18:00-02:00 at night and the ambulance group were 10:00-18:00. The number of visits for top 5 system diseases were trauma, digestive system, other diseases, respiratory system and urinary system diseases in self-visiting group; and were nervous system, trauma, digestive system, respiratory system and circulatory system diseases in ambulance group. The hospitalization rates of self-visiting group and ambulance group were 14.41% (3 006/20 856) and 76.64% (1 564/2 183), respectively.


Conclusion
The emergency patients with different visiting modes have different characteristics. The information would be useful for rationally allocate emergency resources, optimize the treatment process, improve the emergency capacity and ensure the safety of patients.


Key words: 
Emergency service, hospital; Epidemiology; Epidemics; Ambulances; Hospitalization
合理调血脂
Authors: 顼志敏, 刘岚
Journal: BMJ (2008)

顼志敏:心脑血管病死亡率在中国人口总死亡率中居首位.近20余年,我国脑卒中发病率居高不下,冠心病发病率和死亡率也显著上升.北京的监测结果显示,1984年至1999年,出血性脑卒中发病率有明显下降趋势,而缺血性脑卒中发病率却明显上升,提示以动脉粥样硬化为基础的缺血性心脑血管病(包括冠心病和缺血性脑卒中)发病率正在升高.研究表明,血清总胆固醇(TC)或低密度脂蛋白胆固醇(LDL-C)升高,是冠心病和缺血性脑卒中的最重要的独立危险因素之一.因此对血脂异常的防治必须及早、长期地高度重视.今天主要和大家讨论血脂异常的调脂治疗。
Comprehensive immune cell analysis from lung cancer patients with PD-1 inhibitor neoadjuvant immunotherapy using single cell sequencing.
Authors: Zhenzhen Hui, Jiali Zhang, Shanshan Xiao, Yue Pu, Rui Lin, Tao Wang, Jian You, Xiubao Ren
Journal: Journal of Clinical Oncology (2020)

e21001 Background: Single-cell RNA sequencing (scRNA-seq) is a powerful tool to investigate the tumor microenvironment including infiltration of different types of immune cells. However, there is limited study utilizing scRNA-seq technology to investigate patient response to immunotherapy using a comprehensive set of samples. In this study, we used scRNA-seq approach to study tumor infiltrating immune cells in lung cancer patients receiving PD-1 inhibitor neoadjuvant immunotherapy. Methods: CD45 cells were collected from the tumor tissues, the adjacent normal tissues, peripheral blood, lymph nodes, and normal lung tissues for three lung cancer patients receiving PD-1 inhibitor neoadjuvant immunotherapy and four treatment naive lung cancer patients, followed by single cell library construction using 10x Genomics technology and sequenced on Illumina HiSeq X-Ten platform. CellRanger was used to generate expression matrices, and Seurat was used to identify cell subpopulations. Results: From a total of 62,970 single cells, we identified 23 clusters that belonged to different types of immune cells including myeloid cells, T cells, NK cells, mast cells, and B cells. Compared with the adjacent normal tissues, the tumor tissues had lower proportion of NK cells and higher percentage of B cells in all but one patient, and higher percentage of Treg cells for all the seven patients. We observed that patients treated with neoadjuvant immunotherapy had higher proportion of tumor-infiltrating T cells and lower percentage of myeloid cells compared with the treatment naive patients. Patients in the two groups showed differential gene expression in categories including leukocyte cell-cell adhesion, and cell-cycle arrest. Furthermore, the three patients undergoing immunotherapy had different response; the gene expression pattern for the patients differed in functional groups including regulation of inflammatory response, leukocyte migration, and regulation of immune effector process. These results support the potential application for scRNA-Seq in monitoring patient response to neoadjuvant immunotherapy. Conclusions: scRNA-Seq technology can detect the composition of tumor-infiltrating immune cells after neoadjuvant immunotherapy, which provides new tool for predicting the efficacy of treatment. We will next focus on the gene expression of tumor-infiltrating Treg cells and its effect on the therapeutic response.
Incidence of Treatment for Opioid Use Disorder Following Nonfatal Overdose in Commercially Insured Patients
Authors: Austin S. Kilaru, Aria Xiong, Margaret Lowenstein, Zachary F. Meisel, Jeanmarie Perrone, Utsha Khatri, Nandita Mitra, M. Kit Delgado
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Timely initiation and referral to treatment for patients with opioid use disorder seen in the emergency department is associated with reduced mortality. It is not known how often commercially insured adults obtain follow-up treatment after nonfatal opioid overdose. <h3>Objective</h3> To investigate the incidence of follow-up treatment following emergency department discharge after nonfatal opioid overdose and patient characteristics associated with receipt of follow-up treatment. <h3>Design, Setting, and Participants</h3> A retrospective cohort study was conducted using an administrative claims database for a large US commercial insurer, from October 1, 2011, to September 30, 2016. Data analysis was performed from May 1, 2019, to September 26, 2019. Adult patients discharged from the emergency department after an index opioid overdose (no overdose in the preceding 90 days) were included. Patients with cancer and without continuous insurance enrollment were excluded. <h3>Main Outcomes and Measures</h3> The primary outcome was follow-up treatment in the 90 days following overdose, defined as a combined outcome of claims for treatment encounters or medications for opioid use disorder (buprenorphine and naltrexone). Analysis was stratified by whether patients received treatment for opioid use disorder in the 90 days before the overdose. Logistic regression models were used to identify patient characteristics associated with receipt of follow-up treatment. Marginal effects were used to report the average adjusted probability and absolute risk differences (ARDs) in follow-up for different patient characteristics. <h3>Results</h3> A total of 6451 patients were identified with nonfatal opioid overdose; the mean (SD) age was 45.0 (19.3) years, 3267 were women (50.6%), and 4676 patients (72.5%) reported their race as non-Hispanic white. A total of 1069 patients (16.6%; 95% CI, 15.7%-17.5%) obtained follow-up treatment within 90 days after the overdose. In adjusted analysis of patients who did not receive treatment before the overdose, black patients were half as likely to obtain follow-up compared with non-Hispanic white patients (ARD, −5.9%; 95% CI, −8.6% to −3.6%). Women (ARD, −1.7%; 95% CI, −3.3% to −0.5%) and Hispanic patients (ARD, −3.5%; 95% CI, −6.1% to −0.9%) were also less likely to obtain follow-up. For each additional year of age, patients were 0.2% less likely to obtain follow-up (95% CI, −0.3% to −0.1%). <h3>Conclusions and Relevance</h3> Efforts to improve the low rate of timely follow-up treatment following opioid overdose may seek to address sex, race/ethnicity, and age disparities.
Comparison of advanced care discussions between Chinese-American and Caucasian stage IV cancer patients at a single American cancer center.
Authors: Avery Glover, Courtney Schroeder, Emma Ernst, Tamara Vesel
Journal: Journal of Clinical Oncology (2020)

e19081 Background: Timely discussions with cancer patients on prognosis, goals of care (GOC), and end-of-life care (EOLC) are essential components of quality care for diverse populations. Although Chinese-Americans represent one of the fastest growing ethnic groups in the United States, little is known about the utilization of these advanced care discussions with Chinese-American cancer patients. Methods: In this exploratory review, we collected data for 63 Chinese-American and 63 Caucasian stage IV solid cancer patients at a tertiary medical center who died 2013-2018. The following data points were compared: frequency and timing of prognosis, GOC, and EOLC discussions; family inclusion in discussions; healthcare proxy identification; DNR completion. Results: Chinese-American and Caucasian patients had similar frequencies of prognostic (76% vs 71%), GOC (51% vs 56%), and EOLC discussions (89% vs 84%). For all three types of conversations, Chinese-American patients had the discussions earlier on average (days before death: prognosis 86 vs 62; GOC 54 vs 37; EOLC 69 vs 48) and included family members in the discussions more often (30% vs 15%). Chinese-Americans identified healthcare proxies earlier (50 vs 45 days before death). Chinese-Americans had DNR orders placed later (29 vs 33 days before death) and were more likely to have DNR orders placed on the day of death (30% vs 23%). Conclusions: Despite similar frequency of advanced care discussions, earlier conversations, and earlier identification of healthcare proxies in the Chinese-American group, DNR orders were placed later and were often delayed until the day of death for Chinese-American patients. Further studies are needed to better explore the differences indicated in this preliminary study.
Correlation between DIDO1 variation and MSI-status in colorectal cancer.
Authors: Xingwei Zhang, Yonghua Cai, Yujie Hou, Huanxin Hu, Yaoxu Chen, Mengli Huang, Liang Kang
Journal: Journal of Clinical Oncology (2020)

e16054 Background: Several studies have displayed a sustained clinical response to immune checkpoint inhibitors with profound clinical improvement in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC). MSI-H tumors may display higher numbers of TILs, many of which can be directed against tumor-related neoantigens. We set out to examine the underline mechanism in gene level to further explain the differences between MSI-H and MSS CRC. Methods: Whole exome sequencing(WES) was performed on 68 CRC patient.MSI status of these patients were determined using a targeted next generation sequencing panel covering 100 MSI loci. TCGA database was used to analyze WES data of 364 CRC patients with different MSI states, and immune signature was used to analyze the corresponding relationship of immune cell expression in different populations. Results: Of 56 MSS patients, 58.9% (33/56) had copy number variants (CNV) in DIDO1, and 1.8 (1/56) had single nucleotide variants(SNV) in DIDO1. Of 12 MSI-H patients, 33.3% (4/12) had SNV in DIDO1 gene, None had CNV in DIDO1. TCGA database showed that of 308 MSS patients, 8% (24/308) had CNV in DIDO1 and 3% (9/308) had SNV in DIDO1. Of 56 MSI-H patient, 39% (22/56) had SNV in DIDO1 and only one patent had both SNV and CNV in DIDO1. Gene variation of DIDO1 of 68 CRC patients showed a correlation with TCGA database. Gene variation of DIDO1 in MSI-H patients are mainly SNV, and the incidence of CNV is very small (4.3% of DIDO variation).While, gene variation of DIDO1 in MSS patients are mainly CNV, followed by SNV, indicating DIDO1 CNV are highly possible occurring in MSS patients. Furthermore we analyzed the relationship between the copy number of DIDO1 and immune signature through CRC TCGA database. The results showed increase of DIDO1 copy number was negatively correlated with the abundance of NK cells (P = 0.00048), T cells (P = 8.23×10-5) and macrophages (P = 1.75×10-8). Conclusions: Our results showed that different MSI status display unique patent of DIDO1 gene variation, which may be related to different immune micro environment among MSI-H/MSS patients.
Risk factors of disease progression and adverse pregnancy outcome in patients with systemic lupus erythematosus during pregnancy
Authors: Weinian Li, Xiaoyan Cai, Xiaojun Lin, Chun Tang, Jinghua Ye, Zhixiang He
Journal: BMJ (2017)

Objective
To investigate the risk factors of disease progression and adverse pregnancy outcome in patients with systemic lupus erythematosus (SLE) during pregnancy.


Methods
Clinical data of 118 pregnant women with SLE admitted from June 2004 to October 2015 were retrospectively analyzed. The patients were divided into selective pregnant group (group A, n=72 cases) and non-selective pregnant group (group B, n=46) according to the disease activity of SLE. The disease progression and pregnancy outcomes were compared between two groups.


Results
The various system damages occurred in group B, including hematological damage in 16 cases, kidney damage in 19 cases, erythra in 10 cases, arthritis in 10 and serositis in 12 cases; while the corresponding cases in group A were 10, 14, 6, 4 and 4( χ2=7.133, P= 0.008; χ2=6.658, P=0.010; χ2=4.304, P=0.038; χ2=7.030, P=0.008; χ2=10.095, P=0.001). SLE exacerbation occurred in 28 cases (74%) of group B and 12 cases (17%) of group A (χ2=34.944, P= 0.000). The logistic regression analysis showed that hypocomplementemia, proteinuria, SLEDAI score before pregnancy and positive anti-dsDNA antibody were the risk factors of SLE disease exacerbation during pregnancy. The maternal complications occurred in group B, including pregnancy-induced hypertension in 7 cases, preeclampsia in 10 cases and infections in 11 cases/times; while the corresponding cases (case/time) in group A were 2, 6 and 4 (χ2=4.526, P= 0.033; χ2=4.304, P=0.038; χ2=8.525, P=0.004). There were 14 cases of therapeutic induced labor, 7 case of stillbirth and 27 cases of total fetal loss in group B, while the corresponding cases in group A were 2, 0 and 4 (χ2=18.317, P= 0.000; χ2=9.080, P= 0.003; χ2=40.920, P= 0.000). The logistic regression analysis showed that positive anticardiolipin antibody, proteinuria, SLEDAI score before pregnancy and renal dysfunction during pregnancy were risk factors of fetal loss. There were 87 cases of successful delivery (73.7%), the successful delivery rates were 41.3% (19/46) in group B and 94.4% (68/72) from group A, respectively. The infant complications occurred in group B, including premature birth in 15 cases, low birth weight in 13 cases, neonatal jaundice in 5 cases and mild asphyxia in 5 cases; while the corresponding cases in group A were 24, 18, 4 and 2 (χ2=11.442, P=0.001; χ2=11.395, P=0.001; χ2=4.664, P= 0.031; χ2=8.035, P=0.005).


Conclusion
SLE patients whose disease conditions are not well controlled would lead to higher percentage of disease deterioration during pregnancy and worse pregnancy outcomes.


Key words: 
Lupus erythematosus, systemic; Disease progression; Pregnancy outcome