2.Expression of C1GALT1 genes in gastric cancer and its effect on the biological behavior of BGC-823 cells in gastric cancer
Muchuan QIAO ; Junru LI ; Ling LUO ; Tong XIA ; Yanhua CHEN ; Menglong HU ; Hailong XIE
Chinese Journal of Clinical and Experimental Pathology 2024;40(6):603-608
Purpose To investigate the expression of C1GALT1 in gastric cancer and its effect on the biological be-havior of BGC-823 in gastric cancer cells.Methods The ex-pression of C1GALT1 mRNA and protein in gastric cancer tis-sues and normal gastric mucosa,gastric cancer cells and normal gastric mucosal cells was analyzed by bioinformatics,qRT-PCR and Western blot;the transient transfection of siRNA into BGC-823 cells was designed with C1GALT1 cDNA sequence as the target.Transwell assay was used to detect the effect of C1GALT1-siRNA on the migration and invasion ability of BGC-823 cells in gastric cancer.Western blot method detected the expression of epithelial-mesenchymal transition(EMT)-related proteins in BGC-823 after transfection of C1GALT1-siRNA.Re-sults C1GALT1 was highly expressed in gastric cancer tissues and cell lines BGC-823,SGC-7901 and MGC-803,and the ex-pression levels were positively correlated with gastric cancer pathological stages Ⅰ and Ⅱ(P<0.05).After interfering with C1GALT1 in BGC-823 cells,the ability of migration and inva-sion decreased(P<0.05),epithelial cell markers E-cadherin and Claudin-1 protein expression increased,while mesenchymal cell markers vimentin and Slug protein expression decreased(P<0.05).Conclusion C1GALT1 is highly expressed in gastric cancer tissues and cells,silencing of C1GALT1 can inhibit mi-gration and invasion ability of gastric cancer,the mechanism may be related to EMT.
3.Efficacy of venetoclax combined with azacitidine in the treatment of patients with newly diagnosed unfit acute myeloid leukemia
China Modern Doctor 2024;62(1):74-77
Objective To observe the efficacy and safety of VA regimen(venetoclax + azacitidine)in the treatment of patients with newly diagnosed unfit acute myeloid leukemia(AML).Methods From April 2021 to February 2023,55 unfit AML patients who were treated with VA regimen in the First Affiliated Hospital of Anhui Medical University were retrospectively analysed.The therapeutic efficacy and safety of VA regimen were evaluated.Results The median treatment courses of AML patients was 3(1-10),and complete response(CR)/CR with incomplete blood count recovery(CRi)rate was 78.2%and minimal residual(MRD)negative conversion rate was 61.8%after the first treatment course.CR/CRi rate and MRD negative conversion rate increased gradually with the increase of treatment course.Patients with IDH1/IDH2,NPM1,ASXL1 mutations and without TP53 mutations responded well to the VA regimen.The median follow-up time was 9.1(1.2-24.0)months.39 patients survived and 16 patients died.The median overall survival(OS)was 17.4 months.Patients with CR/CRi had significantly longer OS duration than patients with partial response or non-response(P<0.001).Almost all patients had different degrees of anemia,thrombocytopenia,leukopenia.In terms of non-hematological adverse events,infection was the most common.Conclusion The VA regimen achieved a higher treatment response rate in newly diagnosed unfit AML patients,and partial response patients could quickly obtain negative MRD.IDH1/IDH2,ASXL1,NPM1,TP53 mutations may be the predictors of patient outcomes.
4.Identification model of tooth number abnormalities on pediatric panoramic radiographs based on deep learning
Xueqing ZENG ; Bin XIA ; Zhanqiang CAO ; Tianyu MA ; Mindi XU ; Zineng XU ; Hailong BAI ; Peng DING ; Junxia ZHU
Chinese Journal of Stomatology 2023;58(11):1138-1144
Objective:To identify tooth number abnormalities on pediatric panoramic radiographs based on deep learning.Methods:Eight hundred panoramic radiographs of children aged 4 to 11 years meeting the inclusion and exclusion criteria were selected and randomly assigned by writing programs in Python (version 3.9) to the training set (480 images), verification set (160 images) and internal test set (160 images), taken in Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology between November 2012 to August 2020. And all panoramic radiographs of children aged 4 to 11 years taken in the First Outpatient Department of Peking University School and Hospital of Stomatology from June 2022 to December 2022 were collected as the external test set (907 images). All of the 1 707 images were obtained by operators to determine the outline and to label the tooth position of each deciduous tooth, permanent tooth, permanent tooth germ and additional tooth. The deep learning model with ResNet-50 as the backbone network was trained on the training set, validated on the verification set, tested on the internal test set and external test set. The images of test sets were divided into two categories according to whether there was abnormality of tooth number, to calculate sensitivity, specificity, positive predictive value and negative predictive value, and then divided into four types of extra teeth and missing permanent teeth both existed, extra teeth existed only, missing permanent teeth existed only, and normal teeth number, to calculate Kappa values. Results:The sensitivity, specificity, positive predictive value and negative predictive value were 98.0%, 98.3%, 99.0% and 96.7% in the internal test set, and 97.1%, 98.4%, 91.9% and 99.5% in the external test set respectively, according to whether there was abnormality of tooth number. While images were divided into four types, the Kappa value obtained in the internal test set was 0.886, and that in the external test set was 0.912. Conclusions:In this study, a deep learning-based model for identifying abnormal tooth number of children was developed, which could identify the position of additional teeth and output the position of missing permanent teeth on the basis of identifying normal deciduous and permanent teeth and permanent tooth germs on panoramic radiographs, so as to assist in diagnosing tooth number abnormalities.
5.UPF1 increases amino acid levels and promotes cell proliferation in lung adenocarcinoma via the eIF2α-ATF4 axis.
Lei FANG ; Huan QI ; Peng WANG ; Shiqing WANG ; Tianjiao LI ; Tian XIA ; Hailong PIAO ; Chundong GU
Journal of Zhejiang University. Science. B 2022;23(10):863-875
Up-frameshift 1 (UPF1), as the most critical factor in nonsense-mediated messenger RNA (mRNA) decay (NMD), regulates tumor-associated molecular pathways in many cancers. However, the role of UPF1 in lung adenocarcinoma (LUAD) amino acid metabolism remains largely unknown. In this study, we found that UPF1 was significantly correlated with a portion of amino acid metabolic pathways in LUAD by integrating bioinformatics and metabolomics. We further confirmed that UPF1 knockdown inhibited activating transcription factor 4 (ATF4) and Ser51 phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), the core proteins in amino acid metabolism reprogramming. In addition, UPF1 promotes cell proliferation by increasing the amino-acid levels of LUAD cells, which depends on the function of ATF4. Clinically, UPF1 mRNA expression is abnormal in LUAD tissues, and higher expression of UPF1 and ATF4 was significantly correlated with poor overall survival (OS) in LUAD patients. Our findings reveal that UPF1 is a potential regulator of tumor-associated amino acid metabolism and may be a therapeutic target for LUAD.
Activating Transcription Factor 4/genetics*
;
Adenocarcinoma of Lung
;
Amino Acids
;
Cell Proliferation
;
Eukaryotic Initiation Factor-2
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Humans
;
Lung Neoplasms
;
RNA Helicases/metabolism*
;
RNA, Messenger/metabolism*
;
Trans-Activators/metabolism*
6.Rapid screening of SARS-CoV-2 inhibitors via ratiometric fluorescence of RBD-ACE2 complexes in living cells by competitive binding.
Lu MIAO ; Wei ZHOU ; Chunyu YAN ; Yuebin ZHANG ; Qinglong QIAO ; Xuelian ZHOU ; Yingzhu CHEN ; Guangying WANG ; Zhendong GUO ; Jun LIU ; Hailong PIAO ; Xia PAN ; Mengxue YAN ; Weijie ZHAO ; Guohui LI ; Yueqing LI ; Zhaochao XU
Acta Pharmaceutica Sinica B 2022;12(9):3739-3742
7. Clinical efficacy and safety of ixazomib in the treatment of multiple myeloma
Jing BAO ; Xiaowen CHEN ; Liang XIA ; Yuchen ZHAO ; Ruixiang XIA ; Hailong XIA
Chinese Journal of Clinical Pharmacology and Therapeutics 2021;26(7):782-786
AIM: To evaluate the clinical efficacy and safety of oral proteasome inhibitor ixazomib in the treatment of multiple myeloma. METHODS: Eighty patients with multiple myeloma treated with ixazomib-containing therapy in the department of hematology, the First Affiliated Hospital of Anhui Medical University from January 2019 to December 2020 were retrospectively analyzed, including 38 patients with relapsed/refractory multiple myeloma (RRMM)and 42 patients who switched treatment due to adverse events (AEs) after initial induction therapy with bortezomib. Treatment was a two-drug or three-drug regimen containing ixazomib, and the clinical efficacy and safety of ixazomib were evaluated. RESULTS: The overall response rate (ORR) of relapsed/refractory patients was 50%, ≥ VGPR 21.05%; the ORR of patients who switched treatment was 83.33%, compared with the ORR before switching (78.57%), the response rate was further improved, of which 45.24%(19/42) patients had deepened response; the main hematological AEs included granulocyte and platelet count reduction and anemia, non-hematological AEs were mainly diarrhea and fatigue. CONCLUSION: Ixazomib shows good clinical efficacy and safety in patients with RRMM and bortezomib-intolerant MM.
8.Investigation of transmission chain of a cluster COVID-19 cases
Han ZHAO ; Bosong LI ; Yu XIA ; Hailong ZHOU ; Tingrong LI ; Yi ZENG ; Xiaoling ZHU ; Yuxiang ZHOU ; Qin LI
Chinese Journal of Epidemiology 2020;41(12):2015-2019
Objective:To analyze of the transmission characteristics of a cluster of COVID-19 cases in Chongqing and evaluate the infectivity of COVID-19 in the incubation period.Methods:A retrospective survey was conducted by using unified questionnaire through field and telephone interviews among 129 close contacts of COVID-19 cases. The relationship of transmission was indicated by transmission chain, and the infectivity was analyzed by the contact history.Results:This cluster of COVID-19 cases occurred after a classmate party involving members in three families and work fellows in a factory ( R0=3.8). The infection rate during the incubation period was 17.57%. On average, it was infectious three days before onset. There was significant difference in infection rate among different contact modes ( χ2=15.10, P<0.01), There was significant difference in infection rate among single exposureswith different time length ( χ2=25.08, P<0.01). Conclusions:COVID-19 is highly infectious in the incubation period. The more confined the space is, the higher the risk is,and the longer the single exposure is, the higher the risk of transmission is. Indirect contact transmission still exists
9.Emerging roles of DJ-1 in liver diseases through regulation of oxidative stress and immune response
Xu MIN ; Chen LILI ; Li JICHANG ; Wu HAILONG ; Xia QIANG ; Kong XIAONI
Liver Research 2018;2(2):87-91
Reactive oxygen species(ROS)and immune response play critical roles in the progression of liver dis-eases.DJ-1,also known as Parkinson disease 7(Park7),is extensively expressed in cells and tissues,where it governs numerous biological functions including chaperone activity,protease function,tran-scriptional and mitochondrial regulation,and ROS modulation.Moreover,we have established that DJ-1 plays a critical role in initiating an inflammatory response by modulating ROS generation.Therefore,DJ-1 may play an important role in the progression of liver diseases by modulating ROS and the immune response.Recently,we have shown that DJ-1 deficiency negatively regulates proliferation of hepatic progenitor cells(HPCs)by impairing the formation of HPC-associated fibrosis and inflammatory niches.Deficiency of DJ-1 ameliorates liver fibrosis by inhibiting hepatic ROS production and inflammation;moreover,in a classic diethylnitrosamine(DEN)-mediated hepatocellular carcinoma(HCC)mouse model,deletion of DJ-1 ameliorates tumorigenesis and HCC cell proliferation by regulating hepatic inflammation and reducing the activity of the interleukin 6/signal transducer and activator of transcription 3(IL-6/STAT3)signaling pathway.Taken together,these data suggest a critical function for,and therapeutic value of,DJ-1 in treatment of liver diseases.The aim of this review is to summarize these functions and the underlying molecular mechanisms of DJ-1 in liver diseases,and to highlight the potential therapeutic value and future research direction of DJ-1 in liver diseases.
10.Study on cardiovascular disease risk in inpatients with schizophrenia
Shuai ZHAO ; XiaoQin ZHOU ; Hailong XIA ; Jingjing MU ; Long WANG ; Li ZHU ; Anzhen WANG ; YuXia CHEN ; Wanhong YU
Chinese Journal of Nervous and Mental Diseases 2017;43(9):539-543
Objective To describe the cardiovascular risk profile of inpatients with schizophrenia and estimate the 10-year CVD risk in schizophrenia patients. Methods Four hundred sixty-six randomly selected cases of schizophrenia patients and 507 health controls were included in the study. Body mass index (BMI), Fasting blood glucose (FBG), triglyceride (TG),,total cholesterol (TC), smoking rate (smoking people/total people), Framing-ham Risk Score (FRS), high density lipoprotein-cholesterol (HDL-C) and age of the vessel (VA). The 10-year cardiovascular risk(FRS) and age of the vessel (VA) were assessed using the Framing-ham Risk Score. Results 10-year CVD risk was significantly higher in patients with schizophrenia than in control group [(6.71 ±6.95)% vs. (4.76 ±3.07)%], (P<0.05). Comparing with the control group, smoking prevalence[(41%) vs. (19%)], MS[(25%) vs. (17%)], BMI[(23.67 ±3.61)kg/m2 vs. (21.73±4.11)kg/m2] and VA[(46.7±15.3) vs. (43.7±9.8)] were higher in patients group. SBP[(119.86±14.90)mmHg vs. (128.10±15.41)mmHg] and HDL-C [(1.08±0.27)mmol/L vs. (1.38±0.22)mmol/L] were lower in patients group than in the healthy controls. The FRS score of the patient group was positively correlated with BMI, FBG level and SBP, waist circumference and smoking index (P<0.05) and was negatively correlated with the levels of HDL-C. Multivariate Linear Regression analysis demonstrated that FRS was correlated with FBG (β=0.181,P<0.01)、SBP (β=0.149,P<0.01)、HDL-C (β=-0.107,P<0.01) and smoking index(β=0.554,P<0.01). Conclusion The risk of cardiovascular disease in patients with schizophrenia over the next 10 years is 6.7%, which is significantly higher compared with the control group. Fasting blood glucose, systolic blood pressure, high density lipoprotein, smoking may be associated with 10-year CVD risk of schizophrenia patients.

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