1.Comparative Study of Two High-sensitivity Cardiac Troponin 0/3-hour Algorithms for the Diagnosis of Non-ST-segment Elevation Myocardial Infarction in the Chinese Population
Yaoyao CAI ; Yahui LIN ; Qing YANG ; Hong ZHAN ; Min LIU ; Shukui WANG ; Caidong LIU ; Guangxun FENG ; Tao ZHANG ; Yanmin YANG ; Jun ZHU ; Zhou ZHOU ; Yan LINAG
Chinese Circulation Journal 2024;39(11):1070-1077
Objectives:To compare the diagnostic efficacy of non-ST-segment elevation myocardial infarction (NSTEMI) and the predictive value for major adverse cardiovascular events (MACE) of the 0/3-hour algorithm for high-sensitivity cardiac troponin (hs-cTn) recommended by the 2015 European Society of Cardiology (ESC) guidelines for the management of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and the 2021 "Chinese Expert Consensus on Laboratory Testing and Clinical Application of Cardiac Troponin" in suspected acute coronary syndrome (ACS) patients in the Chinese population. Methods:This is a multicenter prospective observational study,including 1527 patients with suspected ACS from three clinical centers from January 2017 to September 2020.Plasma hs-cTnI levels were measured using the ARCHITECT assay at the time of presentation and 3 hours later in patients with suspected ACS (test determination).Clinical judgment (independent clinical judgment by cardiac experts,independent of the test results) was used as the gold standard to compare the sensitivity,specificity,and consistency of the two diagnostic algorithms,and to analyze their predictive value for MACE at 30 days and 180 days.MACE in this study was defined as a composite event of cardiovascular death,myocardial infarction,and unplanned coronary revascularization. Results:According to clinical judgment,there were 400 patients with NSTEMI and 1127 patients without NSTEMI.The 0/3-hour algorithm recommended by the 2021 Chinese Expert Consensus showed higher sensitivity in diagnosing NSTEMI than the 2015 ESC guidelines (91.50%[95% CI:88.32%-94.04%]vs.87.75%[95% CI:84.13%-90.80%]),but slightly lower specificity (93.88%[95% CI:92.32%-95.21%]vs.95.56%[95% CI:94.19%-96.69%]),with both differences being statistically significant (both P<0.001).In the follow-up at 30 days and 180 days,the incidence of MACE in patients diagnosed with NSTEMI by both algorithms was higher than in those without NSTEMI (P<0.001).The incidence of MACE at 30 days and 180 days for the group excluded from the diagnosis of NSTEMI by 2015 ESC guidelines was 0.19% and 1.120%,respectively,and for the NSTEMI group was 2.89% and 3.68%,respectively;for the group excluded from NSTEMI by the 2021 Chinese Expert Consensus,the incidence was 0.096% and 0.770%,respectively,and for the NSTEMI group was 2.91% and 4.36%,respectively.Cox analysis showed that the HR ratio for MACE at 180 days in the NSTEMI group diagnosed by both algorithms was 3.418 and 5.892,respectively,significantly higher than the group excluded from NSTEMI. Conclusions:The 0/3-hour algorithm recommended by the 2021 Chinese Expert Consensus has superior diagnostic sensitivity compared to the 2015 ESC NSTE-ACS guidelines,at the cost of slightly lower specificity.Both algorithms can effectively predict MACE within 180 days,but based on the data from this study,the algorithm recommended by the 2021 Chinese Expert Consensus is more sensitive in predicting the risk of MACE,and patients excluded from the diagnosis of NSTEMI by this method have a lower incidence of MACE,suggesting that its application in clinical practice may be more helpful in terms of long-term safe management of patients.
2.Investigation on the mechanism of EZH2 regulating biological behavior of ovarian cancer cells
Ling ZHU ; Ke WANG ; Feng ZHAO ; Siqi LI ; Shukui WANG ; Qixiang SHAO
Chinese Journal of Clinical Laboratory Science 2024;42(7):542-547
Objective To investigate the mechanism of enhancer of zeste homolog 2(EZH2),a histone methyltransferase,in regula-ting the biological behavior of ovarian cancer(OC)and provide the experimental support for finding new therapeutic targets in the treat-ment of OC.Methods The small interfered RNAs(siRNAs)of EZH2 were used to knock down EZH2 in different OC cell lines,and the interfering efficiency of siEZH2 mRNAs and protein were evaluated by qRT-PCR and Western blot.The cell proliferation,migra-tion,invasion ability and apoptosis of OC cells before and after EZH2 interference were evaluated by the CCK-8,wound healing,Tran-swell and flow cytometry.The expression levels of early growth response 1(EGR1)and H3K27me3 proteins after EZH2 interference were determined by Western blot.Meanwhile,the mechanism of EZH2 regulating the biological behavior of OC cells was explored.Re-sults The expression levels of EZH2 mRNA in OC cells transfected with siEZH2 were significantly lower than that in the negative con-trol group(P<0.05)and the expression levels of EZH2 protein in A2780 cells were also significantly downregulated(P<0.05).The results of Western blot showed that the expression levels of EGR1 and H3K27me3 proteins were reduced to varying degrees.After trans-fection with siEZH2-1,the proliferation ability of A2780 cells in the transfected group was significantly lower than that in the negative control group(P<0.05).The results of the cell scratch test and Transwell test showed that the migration and invasion ability of OC cells transfected with siEZH2-1 were significantly weakened(P<0.05).The results of flow cytometry showed that the apoptosis of OC cells transfected with siEZH2-1 was significantly enhanced(P<0.05).Conclusion EZH2 is highly expressed in OC cells and can promote the proliferation,migration,invasion and anti-apoptosis of A2780 cells.However,EZH2 affects the biological behavior of ovar-ian cancer not by regulating the expression of EGR1 through its H3K27me3 transferase activity.
3.Predictive value of single high-sensitivity cardiac troponin Ⅰ level on the 30-day cardiovascular adverse events in patients with suspected acute coronary syndrome
Dongfang GAO ; Yan LIANG ; Yahui LIN ; Guozheng ZHANG ; Yanmin YANG ; Hong ZHAN ; Min LIU ; Shukui WANG ; Caidong LIU ; Jun ZHU ; Zhou ZHOU
Chinese Journal of Laboratory Medicine 2023;46(5):518-523
Objective:To explore the predictive value of single high-sensitivity cardiac troponin I (hs-cTnI) concentration of 30-day cardiovascular adverse events in patients with suspected acute coronary syndrome (ACS).Methods:This is a multicenter, prospective and observational clinical study. Patients with suspected ACS who were admitted into the emergency department of Fuwai Hospital, the First Affiliated Hospital of Sun Yat-sen University and Nanjing First Hospital from January 2017 to September 2020 were enrolled. hs-cTnI result at the time of visit was obtained from patients with suspected ACS. Patients were followed up for 30 days and patients were divided into no events group and events group according to the presence or absence of 30-day cardiovascular adverse events (acute myocardial infarction (including index), unplanned revascularization and cardiovascular death). The predictive value of single Hs-cTnI at different concentration thresholds on the adverse event was evaluated in terms of sensitivity, negative predictive value (NPV) and 95% confidence interval ( CI). The best threshold was defined as: missed diagnosis rate <2% and NPV >99%. Patients were sub-grouped according to the confounders of hs-cTnI (sex, age, chest pain duration, estimated glomerular filtration rate), and Chi-square test was used to compare sensitivity and NPV among various subgroups. Results:A total of 1 461 patients were included. Among them, 387 patients (26.5%) had 30-day adverse cardiovascular events and 1 074 patients (73.5%) had no adverse cardiovascular events. Mean age was (62±12) years old and 905 were males (61.9%). When the concentration of hs-cTnI was less than 2 ng/L (limit of detection), the missed diagnosis rate of 30-day cardiovascular adverse events was 0.8% (3/387), the sensitivity was 99.2% (95% CI 97.6%-99.8%), and NPV was 98.7% (95% CI 96.0%-99.7%). When hs-cTnI concentration was less than 6 ng/L, the missed diagnosis rate was 1.8%, the sensitivity was 98.2% (95% CI 96.1%-99.2%), and NPV was 99.0% (95% CI 97.9%-99.6%). Subgroup analysis showed that the sensitivity and NPV of single hs-cTnI concentration <6 ng/L for 30-day cardiovascular adverse events were lower in patients with chest pain less than 3 h than those with chest pain time>3 hours ( P<0.05). Conclusions:Single hs-cTnI concentration less than 6 ng/L can predict the risk of 30-day cardiovascular adverse events in suspected ACS patients, but continuous monitoring is recommended for patients with chest pain onset≤3 hours.
4.Chinese Experts Consensus on Immune Checkpoint Inhibitors for Non-small Cell Lung Cancer (2020 Version).
Caicun ZHOU ; Jie WANG ; Baocheng WANG ; Ying CHENG ; Zhehai WANG ; Baohui HAN ; You LU ; Gang WU ; Li ZHANG ; Yong SONG ; Bo ZHU ; Yi HU ; Ziping WANG ; Qibin SONG ; Shengxiang REN ; Yayi HE ; Xiaohua HU ; Jian ZHANG ; Yu YAO ; Hongyun ZHAO ; Zhijie WANG ; Qian CHU ; Jianchun DUAN ; Jingjing LIU ; Shukui QIN
Chinese Journal of Lung Cancer 2021;24(4):217-235
Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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5.Research progress in peptides encoded by non-coding RNA
Junjie NIE ; Xiaoxiang CHEN ; Xiangxiang LIU ; Huiling SUN ; Shukui WANG
Chinese Journal of Laboratory Medicine 2021;44(10):978-982
Non-coding RNA (ncRNA) used to be considered as a class of gene transcripts without protein-coding capacity. Whereas emerging evidence has demonstrated that a small fraction of ncRNAs are still capable of producing functional peptides. Such ncRNAs and corresponding peptides are highly conserved and homologous, and can be detected by sequencing or mass spectrometry analysis. In this paper, we searched several databases with the keywords of "non-coding RNA" and "peptide", and briefly reviewed the characteristics of ncRNA that can be translated into functional small peptides, detection methods of peptides, biological functions of peptides and clinical application value of peptides. The results show that these functional peptides are often involved in disease processes, such as regulation of tumor progression, muscle activity and immune disorders. NcRNA-encoded peptides can be used as novel and efficacious disease diagnostic, therapeutic, and prognostic tools, and further develop as anticancer therapeutic targets to provide new ideas for individual precise treatment of tumors.
6.Chinese Experts Consensus on Immune Checkpoint Inhibitors for Non-small Cell Lung Cancer (2019 version).
Caicun ZHOU ; Jie WANG ; Hong BU ; Baocheng WANG ; Baohui HAN ; You LU ; Zhehai WANG ; Bo ZHU ; Ziping WANG ; Qibin SONG ; Shengxiang REN ; Dongmei LIN ; Yayi HE ; Xiaohua HU ; Hongyun ZHAO ; Shukui QIN
Chinese Journal of Lung Cancer 2020;23(2):65-76
Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients' survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.
7.Overexpression of long noncoding RNA HMMR-AS1 promotes progression of lung adenocarcinoma
Yongjing ZENG ; Tao XU ; Kang LIN ; Bangshun HE ; Yuqin PAN ; Huiling SUN ; Shukui WANG
Chinese Journal of Clinical Laboratory Science 2019;37(5):389-395
Objective:
The purpose of this study is to explore the biological function of long non-coding RNA (lncRNA) HMMR-AS1 in proliferation and metastasis of lung adenocarcinoma (LUAD).
Methods:
Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of HMMR-AS1 and its sense strand HMMR in LUAD cell lines. Then we knock down the HMMR-AS1 expression through small interfering RNA and evaluate the transfection efficiency and its effect on the expression of HMMR. CCK-8 (cell counting kit), clone formation, flow cytometric analysis, wound scratch assay and transwell assay were used to assess the biological function of A549 and H1299 cells. Western blot was used to detect the protein expression of HMMR in the two cell lines after transfection with si-HMMR-AS1.
Results:
The expression of HMMR-AS1 in A549 and H1299 cells of LUAD cell line was markedly higher than that in normal lung epithelial cell BEAS-2A by upregulating approximately 3.06 and 5.02 folds (P<0.05), respectively. After transfection with si-HMMR-AS1, the expression of HMMR-AS1 markedly reduced in both levels of transcription and protein (P<0.05). Furthermore, knocking down of HMMR-AS1 significantly inhibited the proliferation, migration and invasion abilities, and increased the apoptosis rates of A549 and H1299 cells.
Conclusion
LncRNA HMMR-AS1 could promote malignant progression of LUAD cells through enhancing the growth, migration and invasion ability of LUAD cells.
8.Circulation miR-193 cluster serves as a promising biomarker for diagnosis of breast cancer
Bei PAN ; Xuhong WANG ; Shukui WANG ; Bangshun HE
Chinese Journal of Clinical Laboratory Science 2019;37(8):574-578
Objective:
To evaluate circulating miR-193 cluster as a biomarker for diagnosis of breast cancer (BC).
Methods:
A total of 130 BC patients and 45 healthy controls (HCs) were enrolled. The level of miR-193 cluster was analyzed by using GEO database. RT-qPCR was used to evaluate the level of miR-193 cluster in serum of participants. Receivers operating characteristic (ROC) curve analysis was manipulated to investigate their diagnostic value for BC.
Results:
In the screening stage, the results of GEO database indicated the expression of miR-193a-5p and miR-193b were decreased in the serum of BC patients with prior diagnostic value, and the significant decreased expressions of miR-193 cluster members, miR-193a-3p, -5p and miR-193b-3p, were observed in serum of BC patients compared with those in healthy controls by the determination of RT-qPCR(all P <0.01). In the validation stage, the AUCROC of miR-193a-5p and miR-193b-5p were 0.888 (95% CI :0.808-0.969) and 0.954 (95% CI :0.902-1.000), respectively. In addition, the combined AUCROC of these two miRNAs was 0.982 (95% CI :0.966-0.999).
Conclusion
miR-193a-5p and miR-193b-5p in serum could be served as diagnostic biomarker for screening of breast cancer, and the combined detections of the two miRNAs may exhibit more diagnostic efficiency and good clinical application potential.
9.The expressions of c-Met, VEGF, EGFR and HER-2 in the AFP-producing gastric cancer
Yu FANG ; Lin WANG ; Guimei LI ; Yu ZHANG ; Ningrong YANG ; Shukui QIN
China Oncology 2016;26(8):662-669
Background and purpose:Alpha fetoprotein (AFP)-producing gastric cancer (AFPGC) is considered to be a special type of gastric cancer. Currently, the effect on AFPGC is not as good as the common AFP-
negative gastric cancer. Therefore, it is very important to explore clinicopathological features of AFPGC cancer, to improve diagnosis and individualized treatment. This study is to investigate the expressions of hepatocyte growth factor receptor c (c-Met), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER-2) in the AFPGC.Methods:A total number of 44 cases of AFPGC (serum AFP≥10 μg/L) tissues were selected as a test group. There were 30 cases of serum AFP≥200 μg/L. This study collected 30 cases of gastric cancer with normal AFP and 30 cases of hepatocellular carcinoma with increased AFP (serum AFP≥200 μg/L) as 2 control groups. The cases of the 3 groups had the same clinical stage basically. The expressions of c-Met, VEGF, EGFR and HER-2, CD34 were detected by immunohistochemistry (EnVision staining method). Tumor microvessel density (MVD) was calculated by marking CD34, and the results were analyzed. The clinicopathologic parameters were recorded accurately: gender, age, highest level of serum AFP, tumor differentiation, tumor stage, tumor location, lymph node metastasis, liver metastasis, Lauren classiifcation, etc. These patients were followed up regularly. The clinical pathological features of AFPGC patients were investigated.Results:AFPGC clinical characteristics showed that, among 44 cases of AFPGC group, 86.36% (38/44) had lymph node metastasis, 54.55% (24/44) had hepatic metastasis, intestinal type was 36.36% (16/44), diffuse type was 56.82% (25/44), mixed type was 6.82% (3/44). The positive expression rates of c-Met protein in AFPGC, gastric cancer with normal AFP, hepatocellular carcinoma with increased AFP were 73.33% (22/30), 70.00% (21/30) and 53.33% (16/30), respectively. The positive expression rates of VEGF protein were 76.67% (23/30), 56.67% (17/30) and 66.67% (20/30), respectively. The positive expression rates of EGFR protein were 53.33% (16/30), 40.00% (12/30) and 73.33% (22/30), respectively. The “++ and +++” expression rates of HER-2 in AFPGC, gastric cancer with normal AFP and hepatocellular carcinoma with increased AFP were 38.64% (17/44), 23.33% (7/30) and 26.67% (7/30), respectively. The MVD values in AFPGC, gastric cancer with normal AFP and hepatocellular carcinoma with increased AFP were 23.03±10.24, 21.92±11.45 and 19.43±7.83, respectively. Compared with gastric cancer with normal AFP, expression of VEGF protein was signiifcantly higher in the AFPGC (P<0.05). Compared with hepatocellular carcinoma with increased AFP, the expression of c-Met protein was significantly higher in AFPGC (P<0.05).Conclusion:AFPGC is prone to lymph node metastasis and hepatic metastasis. The major part is the diffuse type in Lauren classiifcation. The positive expression rates of VEGF protein in AFPGC were signiifcantly higher than the gastric cancer with normal AFP. The positive expression rates of c-Met protein in AFPGC were signiifcantly higher than the hepatocellular carcinoma with AFP increased.
10.Application of cell sheet technology in tissue engineering
Shukui ZHOU ; Kaile ZHANG ; Ying WANG ; Qiang FU
Chinese Journal of Tissue Engineering Research 2016;20(11):1630-1636
BACKGROUND:The cel sheet technology that is applied with the absence of scaffolds and enzymatic digestion can effectively repair tissue defects and improve organ function, by stimulating the secretion of extracelular matrix to form a dense membrane tissue.
OBJECTIVE: To review the recent progress in cel sheet technology used in tissue engineering, thereby providing a new idea for relevant basic and clinical research.
METHODS:The first author retrieved CNKI database, Wanfang database and PubMed with the keywords of “cel sheet, tissue engineering” in Chinese and English, respectively. Literature retrieval period was from January 2010 to July 2015.
RESULTS AND CONCLUSION:Cel sheet technology combined with scaffold materials can be used for reconstruction and repair of tissues and organs. With the emerging of new technologies, multi-layer cel sheets are stratified to form a three-dimensional tissue for repair of soft tissues and organs. Compared with the monolayer cel sheet, the three-dimensional cel sheet that is laminated by same or different cel sheets has stronger regenerative ability and can be used to construct the ideal target tissue modelin vitro. Cel sheet technology combined with scaffolds can improve the mechanical strength of the composite and reduce cel loss, which has made great progress in the repair of tooth, bone and cartilage tissue. Currently, the cel sheet technology is at the laboratory stage, and little is reported on its clinical applications. We look forward to more innovative technologies that can be integrated into the cel sheet technology.

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