1.CeRNA interaction network and immune manifestation of ferroptosis-related signature genes in rheumatoid arthritis
Tian XIA ; Binglin LI ; Fayuan XIAO ; Enze ZHENG ; Yueping CHEN
Chinese Journal of Tissue Engineering Research 2024;28(16):2561-2567
BACKGROUND:Ferroptosis-related genes have been found to play an important role in the pathogenesis of rheumatoid arthritis.However,there is currently a lack of immune expression of ferroptosis-related signature genes in rheumatoid arthritis and the construction of competing endogenous RNA(CeRNA)interaction networks.Machine learning,as a powerful signature gene selection algorithm based on bioinformatics,can more accurately identify ferroptosis-related signature genes that dominate the pathogenesis of rheumatoid arthritis. OBJECTIVE:To screen ferroptosis-related signature genes in rheumatoid arthritis using bioinformatics and machine learning methods,and to analyze the correlation between ferroptosis-related signature genes and immune infiltration and the construction of CeRNA network of ferroptosis-related signature genes. METHODS:Rheumatoid arthritis-related microarrays were obtained from the GEO database,and ferroptosis-related genes and their differential gene expression were extracted using R language.The differentially expressed genes were screened using machine learning methods.The LASSO regression and SVM-RFE methods were used for signature gene screening,and the genes filtered by both were re-intersected to finally obtain the signature genes in rheumatoid arthritis.Receiver operating characteristic curves were used to assess the accuracy of the screened signature genes for disease diagnosis.Immune infiltration of rheumatoid arthritis and normal synovial tissues was analyzed using the CIBERSORT algorithm,and the correlation between the signature genes and immune cells was analyzed.Finally,the CeRNA network of ferroptosis-related signature genes for rheumatoid arthritis was constructed and the disease signature genes were validated. RESULTS AND CONCLUSION:A total of 150 ferroptosis-related genes in rheumatoid arthritis were obtained,including 55 up-regulated genes and 95 down-regulated genes.GO and KEGG enrichment analyses identified 18 GO significantly correlated entries and 30 KEGG entries respectively,mainly involving metal ion homeostasis,ferric ion homeostasis and oxidative stress response.Machine learning analysis finally identified disease signature genes GABARAPL1 and SAT1.GSEA analysis found that adipocytokine signaling pathway,drug metabolism cytochrome P450,fatty acid metabolism,PPAR signaling pathway,tyrosine metabolism were mainly concentrated when GABARAPL1 was highly expressed,and chemokine signaling pathway,intestinal immune network on IGA production were mainly concentrated when SAT1 was highly expressed.Immune infiltration analysis found that nine immune cells were significantly different in rheumatoid arthritis and normal synovial tissues,in which plasma cells,T-cell CD8,and T-cell follicular helper were highly expressed and the rest were lowly expressed in the disease group.Single gene and immune cell correlation analysis found that GABARAPL1 was positively correlated with dendritic resting cells,activated NK cells,and macrophage M1,with the most significant correlation with dendritic resting cells,while SAT1 was positively correlated with T cell CD4 and γδ T cells and negatively correlated with NK resting cells.GSVA analysis found that SAT1 was upregulated in ascorbic acid and aldehyde metabolism,while downregulated in B-cell receptor signaling pathway,Toll-like receptor signaling pathway,T-cell receptor signaling pathway,and natural killer cell-mediated cytotoxicity.GABARAPL1 showed a down-regulation trend in PPAR signaling pathway,metabolism of nicotinate and nicotinamide,tryptophan metabolism,fatty acid metabolism,and steroid biosynthesis.Sixty long non-code RNAs may play a key role in the development of rheumatoid arthritis.To conclude,the occurrence of rheumatoid arthritis is significantly correlated with the abnormal expression of rheumatoid arthritis-induced ferroptosis-related signature genes,and the signature genes induce disease development via relevant signaling pathways.By analyzing rheumatoid arthritis-related long non-code RNAs-mediated ceRNA networks,potential therapeutic targets and signaling pathways can be identified to further elucidate its pathogenesis and provide a reference basis for subsequent experimental studies.
2.Study on the Emotional Status and Rights Protection of Participants in Drug Clinical Trials during Epidemic Prevention and Control
Yurong ZHANG ; Rui XU ; Qi ZHANG ; Lili ZHAO ; Enze LI ; Xin WANG ; Li WANG
Chinese Medical Ethics 2023;36(4):443-448
【Objective:】 To analyze the emotional status and follow-up status of the participants in the drug clinical trials in a hospital during the epidemic prevention and control, with a view to maximizing the protection of participants’ rights and interests under special circumstances. 【Methods:】 The general information, depression screening scale (PHQ-9), anxiety screening scale (GAD-7) and subject compliance assessment scale were completed online by participants with gold data questionnaire. At the same time, the status of drug clinical trials under study and the follow-up status of participants under study were collected from November 1, 2021 to December 8, 2021 and from December 9, 2021 to January 24, 2022. Excel software and SPSS18.0 software were used for data statistics and analysis. 【Results:】 During the epidemic prevention and control, there were 20 drug clinical trial projects under way in the hospital. From December 9, 2021 to January 24, 2022, the planned number of visits was 161, and the actual number of visits to the hospital was 84 (52.2%). Plus 24 participants who mailed drugs, the overall visit rate was 67.1%, among which the visit rates of oral drugs, non-oral drugs, and oral drugs combined with non-oral drugs were 79.3%, 71.9%, and 41.0% respectively. From November 1, 2021 to December 8, 2021, the planned number of visits was 166, the actual number of visits to the hospital was 157 (94.6%), and the number of telephone visits accounted for 1.8% of the total planned number of visits. The number of participants who did not take the drug and those who delayed taking the drug were both 0. The total compliance of participants was as high as 80.0%. A total of 40 valid questionnaires were retrieved, and the detection rates of depression and anxiety were 42.5% and 30.0% respectively. 【Conclusion:】 The epidemic prevention and control has a large short-term impact on the follow-up of the participants under study. The formulation of relevant follow-up measures and the conduction of classification management can not only improve the emotions of the participants to a certain extent, but also protect the rights and interests of participants, providing suggestions for the follow-up of participants under emergencies in the future.
3.Influencing factors for lymph node metastasis and prognosis in early gastric cancer
Jingyang HE ; Enze LI ; Pengcheng YU ; Yanqiang ZHANG ; Can HU ; Xiangdong CHENG ; Zhiyuan XU
Chinese Journal of Digestive Surgery 2023;22(9):1093-1099
Objective:To investigate the influencing factors for lymph node metastasis and prognosis in early gastric cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 011 patients with early gastric cancer who were admitted to the Zhejiang Cancer Hospital from January 2010 to December 2019 were collected. There were 561 males and 450 females, aged (58±11)years. All patients underwent radical resection of gastric cancer and the lymph node metastasis of each group was identified according to the pathological examination on patients' surgical specimens. Observation indicators: (1) lymph node metastasis in early gastric cancer; (2) influencing factors for lymph node metastasis in early gastric cancer; (3) influencing factors for prognosis in early gastric cancer. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was analyzed using the non‐parameter rank sum test. Univariate analysis was conducted using the Log-Rank test and Logistic regression model, and multivariate analysis was conducted using the Logistic stepwise regression model and COX step-wise regression model. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-Rank test was used for survival analysis. Results:(1) Lymph node metastasis in early gastric cancer. The lymph node metastasis rate of 1 011 patients with early gastric cancer was 23.640%(239/1 011), in which the lymph node metastasis rate of patients with T1a stage gastric cancer was 11.883%(53/446), and the lymph node metastasis rate of patients with T1b stage gastric cancer was 32.920%(186/565). There were 239 patients with lymph node metastasis mainly concentrated in the first station, including 7 cases with No.1 lymph node metastasis, 11 cases with No.2 lymph node metastasis, 135 cases with No.3 lymph node metastasis, 59 cases with No.4 lymph node metastasis, 39 cases with No.5 lymph node metastasis, 91 cases with No.6 lymph node metastasis, 6 cases with No.7 lymph node metastasis, 8 cases with No.8 lymph node metastasis, 8 cases with No.9 lymph node metastasis and 6 cases with No.10 lymph node metastasis. Multiple lymph node metastases may exist in the same patient. For lymph node metastasis in different tumor sites, there were 4 cases, 2 cases and 1 case of lymph node metastasis in the No.2, 3 and 5 lymph node in patients with upper gastric cancer. There were 3 cases, 7 cases, 36 cases, 15 cases, 3 cases and 5 cases of lymph node metastasis in the No.1, 2, 3, 4, 5 and 6 lymph node in patients with middle gastric cancer. There were 4 cases, 97 cases, 44 cases, 35 cases and 86 cases of lymph node metastasis in the No.1, 3, 4, 5 and 6 lymph node in patients with lower gastric cancer. (2) Influencing factors for lymph node metastasis in early gastric cancer. Results of multivariate analysis showed that tumor diameter, tumor location, degree of tumor invasion, vascular thrombus, degree of tumor differentiation were independent factors influencing lymph node metastasis in early gastric cancer ( odds ratio=1.80, 1.49, 2.65, 5.76, 0.60, 95% confidence interval as 1.29-2.50, 1.11-2.00, 1.81-3.88, 3.87-8.59, 0.48-0.76, P<0.05). (3) Influencing factors for prognosis in early gastric cancer. All 1 011 patients were followed up for 43(range, 0-135)months, and the 3-year overall survival rate was 97.32%. Results of multivariate analysis showed that age >60 years and lymph node metastasis were independent risk factors influencing prognosis in early gastric cancer ( hazard ratio=9.50, 2.20, 95% confidence interval as 3.31-27.29, 1.00-4.87, P<0.05). Results of further analysis showed that the 3-year overall survival rate was 99.37% and 94.66% in patient with age >60 years and ≤60 years, respectively, showing a significant difference between them ( χ2=25.33, P<0.05). The 3-year overall survival rate was 95.42% and 97.92% in patients with and without lymph node metastasis, respectively, showing a significant difference between them ( χ2=5.69, P<0.05). Conclusions:The lymph node metastasis rate of early gastric cancer can reach 23.640%. Tumor diameter, tumor location, degree of tumor invasion, vascular thrombus, degree of tumor differentia-tion are independent factors influencing lymph node metastasis in early gastric cancer, age >60 years and lymph node metastasis are independent risk factors influencing prognosis.
4.Effect of percutaneous transhepatic one-step biliary fistulation combined with rigid choledochoscopy in the treatment of benign hepatic bile duct strictures
Yongqing YE ; Jun FENG ; Enze LI ; Jinglin GONG ; Ping WANG
Chinese Journal of Hepatobiliary Surgery 2023;29(7):528-532
Objective:To investigate the therapeutic effect of percutaneous transhepatic one-step biliary fistulation (PTOBF) combined with rigid choledochoscopy in the treatment of benign hepatic bile duct strictures.Methods:The clinical data of 46 patients with hepatic ductal stenosis and stones undergoing PTOBF combined with rigid choledochoscopy at the First Hospital of Guangzhou Medical University between September 2016 and September 2022 were retrospectively analyzed, including 20 males and 26 females, aged (48.5±17.6) years. The location of stones and strictures, stone retrieval rate, postoperative complications, stricture release rate, stone recurrence rate, and reoperation rate were analyzed to access the safety and effectiveness of this procedure.Results:A total of 58 sites of stenoses were found in 46 patients, and PTOBF lithotripsy combined with rigid choledochoscopy were performed for 77 times. The early postoperative complication rate was 19.6% (9/46), and the stenosis release rate was 93.5% (43/46). The mean follow-up time was (28.1±19.6) months, the complete stone retrieval rate was 91.3% (42/46), the stone recurrence rate was 19.6% (9/46), the reoperation rate was 8.7% (4/46), and the long-term postoperative complication rate was 6.5% (3/46).Conclusion:PTOBF combined with rigid choledochoscopic stenoplasty for benign hepatic duct strictures is a safe and feasible procedure to reduce the stone recurrence and long-term postoperative complications.
5.A retrospective correlation study on bile duct angle and hepatolithiasis in liver segment Ⅵ based on 3D visual technology imaging
Yawen CAO ; Enze LI ; Ping WANG ; Beiwang SUN ; Yongqing YE
Chinese Journal of Hepatobiliary Surgery 2022;28(3):181-184
Objective:To study the correlation between biliary angle and hepatolithiasis in liver segment Ⅵ.Methods:A retrospective analysis of the clinical data of 46 patients with liver segment Ⅵ bile duct stones treated at the First Affiliated Hospital of Guangzhou Medical University from January 2017 to January 2021 was carried out. There were 18 males and 28 females, with the age of (55.7±10.5) years. During the study period, 50 patients with cholecystitis were enrolled to form the control group, which consisted of 19 males and 31 females, with the age of (57.4±14.4) years. The angles of the right hepatic duct and the bile duct in segment Ⅵ were measured by the 3D hepatic visualization model. Univariate and multivariate logistic regressions were used to analyze factors correlated with formation of segment Ⅵ bile duct stones.Results:The angles of the segment Ⅵ bile duct (124.5±23.1)° and the right hepatic duct (83.5±14.4)° in the study group were significantly larger than the control group(111.8±27.7)°, (76.9±14.8)°. The difference was significant ( t=2.44, 2.10, P=0.017, 0.039). Analysis showed that the angles of segment Ⅵ bile duct ( OR=1.024, 95% CI: 1.006-1.042, P=0.010) and right hepatic duct ( OR=1.035, 95% CI: 1.005-1.065, P=0.020) correlated with bile duct stones in segment Ⅵ, with greater the angles, greater were the rates of bile duct stones in segment Ⅵ. Receiver operating characteristic curve showed that stones were more commonly formed when the angle of bile duct in segment Ⅵ was over 102.295°. The sensitivity, specificity and area under the curve were 91.3%, 34.0% and 0.631 respectively. Conclusion:The angles of segment Ⅵ bile duct and right hepatic duct were risk factors associated with segment VI bile duct calculi.
6. A Rapid Method for the Separation and Enrichment of Exosomes from Tissues
Jian-Li WANG ; Zi-Yi ZHANG ; Rui YANG ; Wei-Wei QING ; Cheng-Cheng WANG
Chinese Journal of Biochemistry and Molecular Biology 2022;38(3):365-371
The study demonstrates a quick approach for isolating exosomes with substantial concentration. To achieve quality and substantial concentration and purification of exosomes, the target tissue wasmechanically chopped and introduced to tissue digesting enzyme for tissue digestion and filtration. Thetissue cell solution was then subjected to differential centrifugation, ultra-separation, SEC exclusion, andultrafiltration. The protein contents of enzymatic treatment of dissociated tissue were higher as compared toprotein elution of exosome tissue dissociation method. The nanoparticles were traced and seen using atransmission electron microscope after enrichment of exudate to mouse heart, liver, kidney, human coloncancer, human breast cancer, and atherosclerotic tissues. The finding of the study demonstrated that thediameter of the exocrine body was within 30-150 nm, and the structure was obvious and distinct. Westernblots analysis showed that CD9, Alix, and CD63 expression were high, whereas, the TSG101 expressionwas low but calnexin was negative. However, in comparison to other ways, whole process takes only 4-5hours and saves time for quantification and functional analysis of exosomes. The isolated exosomes hashigher purification with less soluble heteroprotein contamination. Advances in isolation exosomes frommicro tissue samples can be employed for nanoparticle size tracking, Western blotting, transmission electron microscopy, and transcriptomic analysis for future studies.
7.Taizhou's COVID-19 prevention and control experience with telemedicine features.
Cenyi SHAO ; Shijian LI ; Feng ZHU ; Dahai ZHAO ; Hui SHAO ; Haixiao CHEN ; Zhiruo ZHANG
Frontiers of Medicine 2020;14(4):506-510
The outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly around the world. As of May 30, 2020, a total of 84 568 confirmed COVID-19 cases have been recorded in China, with a mortality rate of approximately 5.5%. Taizhou is a prefecture-level city in Zhejiang Province. A total of 146 cases were diagnosed in this epidemic, with a fatality rate of 0%. This condition is due to the establishment of an "Internet +" diagnosis and treatment model based on online medical application (APP), telemedicine, WeChat service, and consultation hotline in Taizhou. Taizhou led in opening the "COVID-19 Prevention and Treatment Special Line" in China, which is conducive to pre-hospital screening, suppressing social panic, and clinical support. Hospitals also carried out related online lectures and popularization of science. We summarize Taizhou's COVID-19 prevention and control experience with telemedicine features, with a view to providing reference for the control of the epidemic at home and abroad.
Betacoronavirus
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China
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Coronavirus Infections
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prevention & control
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Humans
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Internet
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Pandemics
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prevention & control
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Pneumonia, Viral
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prevention & control
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Telemedicine
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organization & administration
8. Early antiviral therapy of abidor combined with lopinavir/ritonavir and re-combinant interferonα-2b in patients with novel coronavirus pneumonia in Zhejiang: A multicenter and prospective study
Runan WEI ; Nanhong ZHENG ; Xiangao JIANG ; Chunlian MA ; Xiaowei XU ; Shourong LIU ; Yongping CHEN ; Kaijin XU ; Hainv GAO ; Jiansheng ZHU ; Qiang SHU ; Jifang SHENG ; Xiaoqiang ZHANG ; Minghui LI ; Yan ZHANG ; Mengjie MA ; Xuan ZHANG ; Shibo LI ; Qiujing WANG ; Lingjun YING ; Yongjun ZHANG ; Yunzhen SHI ; Lingyan FAN ; Wanjun YU ; Huaying WANG ; Dandan SUN ; Xiaodong WANG ; Jichan SHI ; Yinghu CHEN ; Xinsheng XIE ; Yunqing CHEN ; Weihong WANG ; Zhaowei TONG ; Lingling TANG ; Mengfei ZHU ; Lingjian ZHANG ; Lanjuan LI
Chinese Journal of Clinical Infectious Diseases 2020;13(0):E010-E010
Objective:
Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province.
Methods:
A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data.
Results:
The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (
9.A clinical study of Chuanhu anti-gout mixture in the treatment of acute gouty arthritis
Xiaolong YU ; Yang LI ; Enze LI ; Changgui LI ; Yan'gang WANG ;
Chinese Journal of Endocrinology and Metabolism 2014;30(1):49-51
In this double-blind,double-dummy,non-inferiority study,144 cases of newly diagnosed acute gouty arthritis were reassigned to Chuanhu anti-gout mixture group (CH,n =72) and colchicine group (Col,n =72).After treatment for 10 days,the total efficiency rates of CH and Col groups were 93.02% and 95.35%,respectively,showing no difference between two groups.Three months later,the overall recurrence rates in CH and Col groups were 12.50% and 13.89% respectively (P<0.05).The incidence of adverse reactions in colchicine group was significantly higher than CH group (34.72% vs 2.78%,P < 0.01).Blood uric acid,alanine aminotransferase,aspartate aminotransferase,and creatinine in CH group were decreased significantly compared with Col group (P<0.05 or P<0.01).The results suggest that the clinical efficacy of Chuanhu anti-gout mixture in the treatment of acute gouty arthritis was not inferior to colchicine,but with higher safety.
10.Contrast enhanced ultrasound features of hepatic tumors contained lipid:comparing with MRI ifndings
Yang, LIU ; Enze, QU ; Zhiyan, LI ; Yuejuan, GAO ; Min, CHEN ; Dakun, ZHANG
Chinese Journal of Medical Ultrasound (Electronic Edition) 2014;(3):29-32
Objective To summarize the imaging features of hepatic tumors contained lipid by contrast enhanced ultrasound (CEUS), and compare with MRI ifndings. Methods From July 2010 to December 2012, 17 patients of hepatocellular carcinoma containing lipid component in the 302nd Hospital of the People′s Liberation Army underwent dual-echo sequence MRI imaging. Fifteen patients were conifrmed by enhanced MRI and contrast-enhanced CT, while the other 2 patients were confirmed by pathology. The features of ultrasonography, CEUS and MRI were analyzed. Kappa analysis test was analyzed for the consistency of CEUS and MRI ifndings. Results In the two-dimensional ultrasound of 17 lesions, 9 were hypoechoic heterogeneous lesions, 5 were hypoechoic lesions;13 lesions with clear boundaries, 4 lesions with unclear boundaries;peripheral blood lfow signal in 5 lesions and rich blood lfow in 1 lesion were observed by color Doppler ultrasound, 11 lesions had no signiifcant blood lfow signal;15 lesions showed fast high enhancement in CEUS arterial phase, 1 lesion with synchronization enhancement, 1 lesion with mild enhancement;10 lesions showed portal clearance, 1 lesion showed an enhanced synchronization, 1 lesion with mild enhancement;16 lesions showed clearance in delay phase, 1 enhanced lesion showed isoenhancement;6 lesions presented intra-lesion or surrounding patchy, irregular non-enhancement areas. CEUS diagnostic accuracy was 82%(14/17), the diagnostic accuracy of MRI was 88%(15/17). The Kappa consistency test was 0.628, while CEUS and MRI results were in good agreement. Conclusions Performance of hepatocellular lipid-containing ultrasound contrast arterial phase shows non-enhancement areas. Contrast enhanced ultrasound features of lipid-containing hepatocellular carcinoma are valuable for the clinical diagnois.

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