Latest Issue

    Volume 36 , Issue 1 , 2021

      Guideline & Consensus

    • Yang Qiwen, Ma Xiaoling, Hu Fupin, Zhang Jing, Sun Tongwen, Chen Baiyi, Xu Yingchun, Liu Youning, China Medical Education Association, Expert Committee on Infectious Diseases, China Medical Education Association
      Vol. 36, Issue 1, Pages: 1-16(2021) DOI: 10.24920/003864
      Abstract:The polymyxins are important antimicrobial agents against antibiotic-resistant gram-negative bacilli. In 2020, the Clinical and Laboratory Standards Institute modified the clinical breakpoints for polymyxin susceptibility test by eliminating the “susceptible” interpretive category, only reporting intermediate (≤2 mg/L) and resistant (≥4 mg/L). However, the European Committee on Antimicrobial Susceptibility Testing recommended the use of clinical breakpoints of ≤2 mg/L as susceptible and >2 mg/L as resistant. The first-line laboratorians and clinicians in China have been perplexed by the inconsistence of international polymyxin clinical breakpoints and discouraged by the difficulty of conducting polymyxin susceptibility testing. Therefore, it is urgently needed to make it clear for the laboratorians in China to know how to accurately carry out polymyxin susceptibility testing and standardize the interpretation of susceptibility testing results. To this end, the experts from relevant fields were convened to formulate this consensus statement on the testing and clinical interpretation of polymyxin susceptibility. Relevant recommendations are proposed accordingly for laboratorians and clinicians to streamline their daily work.  
      Keywords:polymyxin;antimicrobial susceptibility testing;clinical interpretation;expert consensus   
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      Original Article

    • Wu Bin, Zhou Jianghua, Wang Wenxin, Yang Huilin, Xia Meng, Zhang Binghong, She Zhigang, Li Hongliang
      Vol. 36, Issue 1, Pages: 17-26(2021) DOI: 10.24920/003866
      Association Analysis of Hyperlipidemia with the 28-Day All-Cause Mortality of COVID-19 in Hospitalized Patients
      Abstract:Objective This study aimed to determine the association of hyperlipidemia with clinical endpoints among hospitalized patients with COVID-19, especially those with pre-existing cardiovascular diseases (CVDs) and diabetes. Methods This multicenter retrospective cohort study included all patients who were hospitalized due to COVID-19 from 21 hospitals in Hubei province, China between December 31, 2019 and April 21, 2020. Patients who were aged < 18 or ≥ 85 years old, in pregnancy, with acute lethal organ injury (e.g., acute myocardial infarction, severe acute pancreatitis, acute stroke), hypothyroidism, malignant diseases, severe malnutrition, and those with normal lipid profile under lipid-lowering medicines (e.g., statin, niacin, fenofibrate, gemfibrozil, and ezetimibe) were excluded. Propensity score matching (PSM) analysis at 1:1 ratio was performed to minimize baseline differences between patient groups of hyperlipidemia and non-hyperlipidemia. PSM analyses with the same strategies were further conducted for the parameters of hyperlipidemia in patients with increased triglyceride (TG), increased low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C). Mixed-effect Cox model analysis was performed to investigate the associations of the 28-days all-cause deaths of COVID-19 patients with hyperlipidemia and the abnormalities of lipid parameters. The results were verified in male, female patients, and in patients with pre-existing CVDs and type 2 diabetes. Results Of 10 945 inpatients confirmed as COVID-19, there were 9822 inpatients included in the study, comprising 3513 (35.8%) cases without hyperlipidemia and 6309 (64.2%) cases with hyperlipidemia. Based on a mixed-effect Cox model after PSM at 1:1 ratio, hyperlipidemia was not associated with increased or decreased 28-day all-cause death [adjusted hazard ratio (HR), 1.17 (95% CI, 0.95-1.44), P =0.151]. We found that the parameters of hyperlipidemia were not associated with the risk of 28-day all-cause mortality [adjusted HR, 1.23 (95% CI, 0.98-1.55), P = 0.075 in TG increase group; 0.78 (95% CI, 0.57-1.07), P = 0.123 in LDL-C increase group; and 1.12 (95% CI, 0.9-1.39), P = 0.299 in HDL-C decrease group, respectively]. Hyperlipidemia was also not significantly associated with the increased mortality of COVID-19 in patients accompanied with CVDs or type 2 diabetes, and in both male and female cohorts. Conclusion Our study support that the imbalanced lipid profile is not significantly associated with the 28-day all-cause mortality of COVID-19 patients, even in those accompanied with CVDs or diabetes. Similar results were also obtained in subgroup analyses of abnormal lipid parameters. Therefore, hyperlipidemia might be not a major causative factor for poor outcome of COVID-19, which provides guidance for the intervention of inpatients during the epidemic of COVID-19.  
      Keywords:coronavirus disease 2019 (COVID-19);lipid disorder;mortality;cardiovascular diseases;diabetes   
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    • Liu Ju, Xu Zhijian, Bi Xiaofeng, Sun Ping, Huang Jiaqin
      Vol. 36, Issue 1, Pages: 27-34(2021) DOI: 10.24920/003789
      Abstract:Objective To characterize Chinese families in which both parents and at least one child are diagnosed with malignant diseases and provide reference for cancer screening or early detection in people whose both parents are diagnosed with cancer. Methods Medical records of all clients to the center of cancer screening and prevention of the National Cancer Center/Cancer Hospital between January 2008 and February 2018 were screened to select families in which both parents and at least one child were diagnosed with malignant diseases. The cancer profiles of fathers, mothers, sons and daughters, their age distribution at diagnosis, and similarity of cancers between two generations were analyzed. The proportions of each cancer in males and females of the cohort were compared with corresponding data from the National Cancer Center Registry of China (NCCRC) in 2013. Results Totally 135 families were identified from records of 33 200 clients. Proportion of lung cancer in fathers (40/135, 29.6%) and in mothers (38/135, 28.1%) were higher than the national data (23.9% in males and 14.9% in females, respectively). The proportion of breast cancer in daughters (35/109, 32.1%) was higher than that of mothers (14/135, 10.4%) and the national data (17.1%). In 71 father-son pairs of cancer, 46.5% (33/71) were of the same systematic disease, and 16.9% (12/71) were of the same cancer. These two indexes were 31.2% (n=34) and 10.1% (n=11), respectively in the 109 father-daughter pairs of cancer, 36.6% (n=26) and 8.5% (n=6) respectively in the 71 mother-son pairs of cancer, and 31.2% (n=34) and 20.2% (n=20) respectively in the 109 mother-daughter pairs of cancer. Sons were more likely to suffer from cancers originated from the same system as father’s cancer than daughters (χ 2=4.299, P<0.05), and daughters were more likely to suffer from the same cancer as their mother’s cancer than sons (χ 2=4.506, P<0.05). The age (mean ± standard deviation) of the daughters (52.4±12.7) and the sons (59.4±10.9) at diagnosis were significantly younger than the fathers (65.5±12.2) and the mothers (65.7 ±12.5) (all P<0.001). Conclusions For people whose both parents are diagnosed as cancer, screening or early detection examinations should cover a full range of cancers rather than the cancers their father and mother have suffered, or cancers stemmed from the same system as their parent’s cancers. We suggest screening or early detection program for these special population start earlier than that for the general population, with emphasis on cancers derived from digestive system for males and women-specific cancers, i.e., breast cancer, ovarian cancer, cervical cancer and uterine cancer for females.  
      Keywords:family history;parents;daughter;son;early detection;malignant tumor   
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    • Lv Jie, Yuan Jie, Xu Chaojian, Hao Jiaqi, Qin Yichuan, Wang Xiaoqiang, Wang Yongfeng
      Vol. 36, Issue 1, Pages: 35-42(2021) DOI: 10.24920/003753
      VEGF-C/VEGFR-3/iNOS Signaling in Osteosarcoma MG63 Cells Mediates Stimulatory Effects on Human Umbilical Vein Endothelial Cell Proliferation
      Abstract:Objective To assess the effects of vascular endothelial growth factor-C (VEGF-C)/vascular endothelial growth factor receptor-3 (VEGFR-3) signaling on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in human osteosarcoma MG63 cells and the subsequent impact on the proliferation of human umbilical vein endothelial cells (HUVECs). MethodsMG63 cells were treated with VEGF-C alone (VEGF-C group), VEGF-C + iNOS inhibitor aminoguanidine (AG; AG group), and VEGF-C + VEGFR-3 inhibitor MAZ51 (MAZ51 group); untreated MG63 cells were used as controls. NO production was evaluated by a colorimetric method involving nitrate reductase. Meanwhile, mRNA and protein levels of iNOS were examined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. To explore the effect of VEGF-C/VEGFR-3/iNOS signaling of MG63 cells on proliferation of HUVECs, we set up six groups: HUVECs, HUVECs+MG63, HUVECs+VEGF-C, HUVECs+MG63+VEGF-C, HUVECs+MG63+VEGF-C+AG, and HUVECs+MG63+VEGF-C+MAZ51 groups. The proliferation of HUVEC cells was assessed by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2’-deoxyuridine (EdU) incorporation assay, and proliferating cell nuclear antigen (PCNA) expression quantitation. ResultsVEGF-C treatment enhanced iNOS expression at both gene and protein levels (mRNA: LSD-t=4.152, P<0.01; protein: LSD-t=3.486, P<0.01) and increased NO release of MG63 cells (LSD-t=3.774, P<0.01); treatment with either AG or MAZ51 decreased these effects (mRNA: LSD-t=9.183, P<0.001; LSD-t=8.639, P<0.001; protein: LSD-t=5.170, P<0.001; LSD-t=7.255, P<0.001; NO production:LSD-t=10.326, P<0.001; LSD-t=10.540, P<0.001). Interestingly, co-incubation of HUVECs with MG63 cells and/or VEGF-C significantly promoted HUVEC proliferation (EdU: LSD-t=5.374, P<0.001; LSD-t=2.984, P<0.05; LSD-t=8.526, P<0.001; PCNA: LSD-t=9.267, P<0.001; LSD-t=5.515, P<0.001; LSD-t=14.873, P<0.001).The proliferation effects of HUVEC induced by MG63 cells and VEGF-C attenuated by the treatment of AG (EdU: LSD-t=10.770, P<0.001; PCNA: LSD-t=19.940, P<0.001) or MAZ51 (EdU: LSD-t=6.950, P<0.001; PCNA: LSD-t=14.001, P<0.001). ConclusionIn human osteosarcoma MG63 cells, activation of VEGFR-3 by VEGF-C promotes iNOS expression and NO production, which subsequently induces HUVEC proliferation.  
      Keywords:osteosarcoma;VEGF-C;VEGFR-3;iNOS;tumor angiogenesis   
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    • Wang Yi, Wu Chanyuan, Wang Qian
      Vol. 36, Issue 1, Pages: 43-49(2021) DOI: 10.24920/003861
      Bamboo Nodes of Vocal Fold—A Clinical Study of 14 Cases
      Abstract:Objective Bamboo node (BN) of vocal folds is a rare disease which is mostly associated with autoimmune diseases and always involves women as reported in literature. The purpose of this study is to investigate the clinical characteristics and the treatments in a series of BN cases. Methods We retrospectively collected and reviewed clinical information of all patients who presented bamboo nodes by fibreoptic laryngoscopy from 2011 to 2020 in our hospital, including the demographic information, clinical symptoms, associated autoimmune diseases, voice abuse, treatments, and outcomes. Patients were followed up periodically at clinics with fibreoptic laryngoscopy and/or voice recovery evaluation using the self-assessed voice visual analog scale (VAS). Results Totally 14 patients were diagnosed with BN and were included in the study. BN involved both women (8/14, 57.1%) and men (6/14, 42.9%). Bilateral lesions were found in 13 patients (92.9%). The most common symptom of BN was hoarseness (100%). Ten (71.4%) of 14 patients experienced voice abuse. Thirteen (92.9%) of them were concomitant with autoimmunity disease, and received medication therapy for the underlying autoimmune diseases; one patient received anti-acid treatment for the gastroesophageal reflux disease. Voice rests were performed in all patients. Voice recovered completely in 3 cases (21.4%), improved remarkably in 8 cases (57.1%), improved slightly in 1 case (7.1%), and no improvement in 2 cases (14.3%). Conclusions BNs are mostly associated with autoimmune disease and vocal abuse. It may occur in both females and males. Conservative treatment for the underlying autoimmune diseases and vocal rest are beneficial to voice recovery in most of the patients, and can be used as the first choice of treatment.  
      Keywords:bamboo nodes;autoimmune disease;hoarseness;voice abuse;conservative treatment   
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    • Zu Honglin, Hou Likun, Liu Hongwei, Zhan Yuanbo, He Ju
      Vol. 36, Issue 1, Pages: 50-56(2021) DOI: 10.24920/003711
      Identify Candidate Genes in the Interaction between Abdominal Aortic Aneurysm and Type 2 Diabetes Mellitus by Using Biomedical Discovery Support System
      Abstract:Objective To explore the candidate genes that play significant roles in the interconnection between abdominal aortic aneurysm (AAA) and type 2 diabetes mellitus (DM). Methods We used the Biomedical Discovery Support System (BITOLA) to screen out the candidate intermediate molecular (CIM) “Gene or Gene Product” that are related to AAA and DM. The dataset of GSE13760, GSE7084, GSE57691, GSE47472 were used to analyze the differentially expressed genes (DEGs) of AAA and DM compared to the healthy status. We used the online tool of Venny 2.1 assisted by manual checking to identify the overlapped DEGs with the CIMs. The Human eFP Browser was applied to examine the tissue specific expression levels of the detected genes in order to recognize strong expressed genes in both human artery and pancreatic tissue. Results There were 86 CIMs suggested by the closed BITOLA system. Among all the DEGs of AAA and DM, 8 genes in GSE7084 (ISG20, ITGAX, DSTN, CCL5, CCR5, AGTR1, CD19, CD44) and 2 genes in GSE13760 (PSMD12, FAS) were found to be overlapped with the 86 CIMs. By manual checking and comparing with tissue-specific gene data through Human eFP Browser, the gene PSMD12 (proteasome 26S subunit, non-ATPase 12) was recognized to be strongly expressed in both the aorta and pancreatic tissue. Conclusion We proposed a hypothesis through text mining that PSMD12 might be involved or potentially involved in the interconnection between AAA and DM, which may provide a new clue for studies on novel therapeutic strategies for the two diseases.  
      Keywords:abdominal aortic aneurysm;diabetes mellitus;Biomedical Discovery Support System;text mining;gene expression profile   
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      Review

    • Chen Qiong, Yang Xuefeng
      Vol. 36, Issue 1, Pages: 57-65(2021) DOI: 10.24920/003737
      Abstract:Hepatocellular carcinoma (HCC) is one of the most common malignancies, and its treatment is limited. With the understanding of key genes and signaling pathways in the occurrence and development of HCC, targeted drugs with high selectivity and low toxicity have been developed continuously, bringing a variety of options for the treatment of advanced HCC. In this article, the research progress on representative drugs of targeted therapy and potential therapeutic targets for HCC are reviewed.  
      Keywords:hepatocellular carcinoma;targeted therapy;genes;signaling pathway;drug   
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      Case Report

    • Li Dasheng, Wang Dawei, Wang Nana, Xu Haiwang, Huang He, Dong Jianping, Xia Chen
      Vol. 36, Issue 1, Pages: 66-71(2021) DOI: 10.24920/003788
      An Insight of the First Community Infected COVID-19 Patient in Beijing by Imported Case: Role of Deep Learning-Assisted CT Diagnosis
      Abstract:In the era of coronavirus disease 2019 (COVID-19) pandemic, imported COVID-19 cases pose great challenges to many countries. Chest CT examination is considered to be complementary to nucleic acid test for COVID-19 detection and diagnosis. We report the first community infected COVID-19 patient by an imported case in Beijing, which manifested as nodular lesions on chest CT imaging at the early stage. Deep Learning (DL)-based diagnostic systems quantitatively monitored the progress of pulmonary lesions in 6 days and timely made alert for suspected pneumonia, so that prompt medical isolation was taken. The patient was confirmed as COVID-19 case after nucleic acid test, for which the community transmission was prevented timely. The roles of DL-assisted diagnosis in helping radiologists screening suspected COVID cases were discussed.  
      Keywords:coronavirus disease 2019;imported cases;computed tomography;deep learning;diagnosis   
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    • Cao Yanjie, Duan Jingqi, Liu Lifang, Wei Xuan, Ren Li, Zhang Lanning, Zhang Wei
      Vol. 36, Issue 1, Pages: 72-77(2021) DOI: 10.24920/003682
      Individualized Treatment and Palliative Care for A 90-Year-Old Patient with Primary Gastric Diffuse Large-B Cell Lymphoma: 4 Year Follow-up and Inspiration
      Abstract:A 90-year-old man was diagnosed with primary gastric diffuse large B-cell lymphoma (PGDLBL) by PET/CT examination, gastroscopy, biopsy and histopathological analysis at a regular physical check in April, 2016. The patient received R-CO chemotherapy (rituximab, cyclophosphamide, and vincristine) and radiotherapy subsequently, with enteral nutritional treatment through 3-cavity nasogastric tube due to development of pyloric obstruction. To satisfy patient’s strong desire of eating by himself, we performed surgery of exploratory laparotomy and Roux-en-Y gastric bypass (RGB) to relieve pylorus obstruction. Postoperatively, the patient resumed oral feeding, supplemented by nasogastric tube feeding at 1350 - 1550 Kcal daily. He is now 94 years old with fairly well nutrition and normal communication. The outcome of 4 year follow-up suggests that nutritional treatment and palliative medicine are important for improving prognosis and life-quality of very elderly patients with end-stage tumors apart from the effective chemotherapy, radiotherapy, and surgery.  
      Keywords:primary gastric lymphoma;diffuse large B-cell lymphoma;very elderly patient;nutritional treatment;palliative care   
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