1.Targeting NUF2 suppresses gastric cancer progression through G2/M phase arrest and apoptosis induction
Bo LONG ; Huinian ZHOU ; Lixia XIAO ; Xiangyan JIANG ; Jian LI ; Zhijian MA ; Na HE ; Wei XIN ; Boya ZHANG ; Xiaoqin ZHU ; Zeyuan YU ; Zuoyi JIAO
Chinese Medical Journal 2024;137(20):2437-2451
Background::Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2, a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression. Methods::Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2-associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC. Results::NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro. NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models. Conclusions::Collectively, NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.
2.Multi-task learning for automated classification of hypertensive heart disease and hypertrophic cardiomyopathy using native T1 mapping
Honglin ZHU ; Yufan QIAN ; Xiao CHANG ; Yan ZHOU ; Jian MA ; Rong SUN ; Shengdong NIE ; Lianming WU
International Journal of Biomedical Engineering 2024;47(4):342-348
Objective:To automatically classify hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) based on mul-titask learning algorithm using native T1 mapping images.Methods:A total of 203 patients admitted to Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University from January 2017 to December 2021 were enrolled, including 53 patients with HHD, 121 patients with HCM, and 29 patients with normal control (NC). Native T1 mapping images of all enrolled patients were acquired using MRI and processed by a multi-task learning algorithm. The classification performance of each model was validated using ten-fold crossover, confusion matrix, and receiver operator characteristic (ROC) curves. The Resnet 50 model based on the original images was established as a control.Results:The ten-fold crossover validation results showed that the MTL-1 024, MTL-64, and MTL-all models showed better performance in terms of area under the curve (AUC), accuracy, sensitivity, and specificity compared to the Resnet 50 model. In the classification task, the MTL-64 model showed the best performance in terms of AUC (0.942 1), while the MTL-all model reached the highest value in terms of accuracy (0.852 2). In the segmentation task, the MTL-64 model achieved the best results with the Dice coefficient (0.879 7). The confusion matrix plot showed that the MTL model outperforms the Resnet 50 model based on the original image in terms of overall performance. The ROC graphs of all MTL models were significantly higher than the original image input Resnet 50 model.Conclusions:Multi-task learning-based native T1 mapping images are effective for automatic classification of HHD and HCM.
3.Analysis of the whole genome characteristics of influenza A (H3N2) virus in Wuxi city from 2022 to 2023
Yong XU ; Rui WANG ; Chun′an YU ; Jing BAO ; Qi ZHOU ; Yong XIAO ; Hong LI ; Xiaoluan SHI ; Guangyuan MA
Chinese Journal of Experimental and Clinical Virology 2024;38(4):454-463
Objective:To understand the whole genome and genetic evolution characteristics of the first epidemic influenza A (H3N2) viruses in Wuxi from 2022-2023.Methods:Real time fluorescence quantitative RT-PCR method was used to perform typing on respiratory samples of influenza cases. Virus isolation was performed on samples with positive nucleic acid of subtype A H3N2 influenza virus detected. After cell culture, nucleic acid was extracted from strains with red blood cell agglutination test (HA) ≥ 1∶8, whole genome sequence was amplified, library was constructed, and computer sequencing was performed using MiSeq sequencer. Using NC_007366.1 as reference strain, the data were analyzed using CLC Genomics Workbench (Version 23) software. The phylogenetic tree was constructed using MEGA 7.0 software, and the N-glycosylation sites were predicted by NetNGlyc 1.0 Server software.Results:The nucleotide homology and amino acid homology among 35 strains of influenza A H3N2 virus from 2022 to 2023 were 96.4%-100% and 95.2%-100%, respectively. The 16 epidemic strains in 2022 belong to the 3C.2a1b.2a.1a evolutionary branch, while the 19 epidemic strains in 2023 belong to the 3C.2a1b.2a.2a.3a.1 evolutionary branch. There are 7 differences in the nucleotide sequence of the HA gene between the 2022 epidemic strain and the corresponding vaccine strain, sharing 15 mutation sites; There are 28 differences in the nucleotide sequence of the HA gene between the 2023 epidemic strain and the corresponding vaccine strain, sharing 17 mutation sites. The HA genes of 35 epidemic strains all lack N-glycosylation site 61: NSS, while in 2023, the HA genes of 19 epidemic strains added N-glycosylation site 110: NSS.Conclusions:The HA and NA genes of influenza A H3N2 virus in 2022 and 2023 belong to two evolutionary branches, respectively, and both show specific amino acid site changes compared to the corresponding vaccine strains. The antigen matching between the 2022 epidemic strain and the vaccine strain is relatively good, while there is a risk of low antigen matching between the 2023 epidemic strain and the vaccine strain.
4.Surveillance of bacterial resistance in tertiary hospitals across China:results of CHINET Antimicrobial Resistance Surveillance Program in 2022
Yan GUO ; Fupin HU ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Yuling XIAO ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Jingyong SUN ; Qing CHEN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yunmin XU ; Sufang GUO ; Yanyan WANG ; Lianhua WEI ; Keke LI ; Hong ZHANG ; Fen PAN ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Wei LI ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Qian SUN ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanqing ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Wenhui HUANG ; Juan LI ; Quangui SHI ; Juan YANG ; Abulimiti REZIWAGULI ; Lili HUANG ; Xuejun SHAO ; Xiaoyan REN ; Dong LI ; Qun ZHANG ; Xue CHEN ; Rihai LI ; Jieli XU ; Kaijie GAO ; Lu XU ; Lin LIN ; Zhuo ZHANG ; Jianlong LIU ; Min FU ; Yinghui GUO ; Wenchao ZHANG ; Zengguo WANG ; Kai JIA ; Yun XIA ; Shan SUN ; Huimin YANG ; Yan MIAO ; Mingming ZHOU ; Shihai ZHANG ; Hongjuan LIU ; Nan CHEN ; Chan LI ; Jilu SHEN ; Wanqi MEN ; Peng WANG ; Xiaowei ZHANG ; Yanyan LIU ; Yong AN
Chinese Journal of Infection and Chemotherapy 2024;24(3):277-286
Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5%were gram-positive and 70.5%were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3%,76.7%and 77.9%,respectively.Overall,94.0%of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8%of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2%in the isolates from children and 95.7%in the isolates from adults.The resistance rate to carbapenems was lower than 13.1%in most Enterobacterales species except for Klebsiella,21.7%-23.1%of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1%to 13.3%.The prevalence of meropenem-resistant strains decreased from 23.5%in 2019 to 18.0%in 2022 in Pseudomonas aeruginosa,and decreased from 79.0%in 2019 to 72.5%in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.
5.Changing resistance profiles of Staphylococcus isolates in hospitals across China:results from the CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Yuling XIAO ; Mei KANG ; Yi XIE ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Ping JI ; Fengbo ZHANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WEN ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2024;24(5):570-580
Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8%)strains of Staphylococcus aureus and 68,040(33.2%)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)%,wound,pus and secretions(33.6±4.2)%,and blood(11.9±1.5)%.The CNS strains were predominantly isolated from blood(73.6±4.2)%,cerebrospinal fluid(12.1±2.5)%,and pleural effusion and ascites(8.4±2.1)%.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)%,outpatient and emergency(11.6±1.7)%,and department of surgery(11.2±0.9)%,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)%,outpatient and emergency(12.8±4.7)%,and department of internal medicine(11.2±1.9)%.The prevalence of methicillin-resistant strains was 32.9%in S.aureus(MRSA)and 74.1%in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1%to 29.2%,and the prevalence of MRCNS decreased from 82.1%to 68.2%.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2%to 2.3%over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.
6.Design and application of energy monitoring system for laboratory animal facilities
Xiao XU ; Wenjing XIONG ; Xixiang MA ; Dandan MU ; Shunchang ZHOU
Chinese Journal of Comparative Medicine 2024;34(10):88-96
Objective Experimental animal facilities account for a significant proportion of the energy consumption by scientific research institutions;however,the energy consumption characteristics of these facilities differ from those of ordinary buildings,and thus require specialized monitoring and management.Methods A set of energy consumption monitoring systems was designed for experimental animal facilities and deployed in the specific pathogen-free-level experimental animal facility of Huazhong University of Science and Technology.Results The system achieved real-time collection and recording of the facility's electricity consumption data,and proposed energy-saving measures for three application scenarios.Conclusions This energy consumption monitoring system designed for experimental animal facilities is reliable,efficient,and user-friendly,and has the potential to guide and promote energy management programs at experimental animal facilities.
7.Clinical Efficacy of Hypomethylating Agent Therapy in Patients with Chronic Myelomonocytic Leukemia
Xiao LI ; Yan WANG ; Yu-Jie GUO ; Zhi-Yun NIU ; Li MA ; Xu-Quan ZHOU ; Jing-Yu ZHANG
Journal of Experimental Hematology 2024;32(1):257-261
Objective:To observe the clinical efficacy and safety of hypomethylating agent therapy in chronic myelomonocytic leukemia(CMML).Methods:From February 2014 to June 2021,the clinical data,efficacy,survival time and safety of CMML patients diagnosed in the Second Hospital of Hebei Medical University and treated with hypomethylating agent therapy were retrospectively analyzed.Results:A total of 25 CMML patients received hypomethylating agent therapy,including 18 cases treated with decitabine(DEC)and 7 cases treated with azacytidine(AZA)as the basic treatment.Among them,20 patients responded,and 7 patients got complete remission(CR).All patients with CR were treated with DEC as the basic treatment.Five cases of CR occurred in the first 4 courses of treatment.After a median follow-up of 16.4(9.4-20.5)months,4 patients with CR progressed to acute myeloid leukemia(AML).The median overall survival(OS)time of 25 CMML patients was 17.4 months(95%CI:12.437-22.363).According to MD Anderson prognostic scoring system(MDAPS),CMML-specific prognostic scoring system(CPSS),CPSS molecular(CPSS-mol),Mayo molecular model(MMM),risk stratification of patients was performed,and the difference only between different risk stratification of MDAPS and survival time was statistically significant.Common adverse reactions of hypomethylating agent therapy in CMML patients included infection,gastrointestinal reaction,hematological toxicity,skin allergy and liver function damage.All patients'symptoms were improved after corresponding treatment.Conclusion:Hypomethylating agent therapy is effective and safe for CMML patients.CR mostly occurs in the first 4 courses of treatment,and hypomethylating agent therapy combined with low-dose chemotherapy can be used for patients who do not respond.Hypomethylating agent therapy can delay the disease,but can't prevent progression.
8.Safety and efficacy of TBF pretreatment during haploid hematopoietic stem cell transplantation
Wenjuan ZHU ; Shiyuan ZHOU ; Chao MA ; Qian ZHU ; Jing LI ; Xiao MA ; Depei WU ; Xiaojin WU
Chinese Journal of Organ Transplantation 2024;45(2):88-95
Objective:To explore the safety and efficacy of TBF conditioning regimen of thiotepa, fludarabine and busulfan in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for recipients with hematological malignancies unsuitable for BUCY conditioning regimen (busulfan, cyclophosphamide & mBUCY).Method:A retrospective analysis was conducted for 20 recipients with malignant hematologic diseases receiving TBF conditioning regimen before haplo-HSCT at Soochow Hopes Hematologic Hospital from January 2020 to December 2023. The regimen-related toxicity of TBF was assessed by the Bearman scoring criteria. For comparing the safety and efficacy of TBF conditioning regimen with mBUCY regimen, propensity score matching was performed in a ratio of 1: 2 with disease type, patient age and gender as matching factors.Result:Mild oral mucositis and gastrointestinal reaction were major side-effects without severe cardiac events. Median time to neutrophil and platelet engraftments in TBF group was 11 and 18 days with comparable engraftment in mBUCY group. TBF regimen had a significantly lower incidence of grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) than mBUCY at Day 100 (5% vs 35%, P=0.01). No significant inter-group difference existed in overall survival (68% vs 62%, P=0.98) while 1-year incidence of graft-versus-host disease-free, relapse-free survival (GRFS) improved (63% vs 37%, P=0.06) in TBF group. Conclusion:TBF is a promising conditioning regimen with low toxicity and decent safety for haplo-HSCT. TBF patients tend to have a lower incidence of grade Ⅱ-ⅣaGVHD and better GRFS than mBUCY.
9.Eliminating de novo donor specific antibodies with immunoadsorption for improving platelet engraftment after allogeneic hematopoietic stem cell transplantation: one case report
Ling LI ; Jing LI ; Qian ZHU ; Shiyuan ZHOU ; Chao MA ; Shijia LI ; Xiao MA ; Jun HE ; Depei WU ; Xiaojin WU
Chinese Journal of Organ Transplantation 2024;45(3):184-187
To explore the efficacy and safety of immunoadsorption (IA) in removing de novo donor specific antibody (DSA) after allogeneic hematopoietic stem cell transplantation (HSCT), the relevant clinical data were retrospectively reviewed for one female patient of severe aplastic anemia (SAA). Desensitization treatment with IA after HSCT was offered for removing de novo DSA and ultimately promoting platelet engraftment at First Affiliated Hospital of Soochow University in March 2021.
10.Progress and problems in the diagnosis and treatment of immune checkpoint inhibitor related liver injury in cancer
Kaifeng WANG ; Zhongzhong PENG ; Xikai ZHANG ; Xiao ZHOU ; Xianyuan MIAO ; Qiongqiong WANG ; Sijia REN ; Baiwen ZHANG ; Yi WANG ; Yue MA
Tumor 2024;44(1):89-100
The immune related adverse events(irAE)caused by tumor immune checkpoint inhibitors(ICI)have attracted increasing attention of clinical experts.Immune-mediated liver injury caused by ICIs(ILICI)is not uncommon in clinical practice,but specific diagnostic method of ILICI is lacking.Biopsy of liver tissue can help improve the diagnosis and management of ILICI.In the treatment of ILICI,the immediate use of corticosteroid therapy is not necessarily.A balance between efficacy,toxicity,and specific treatment need to be achieved,and further refined through multidisciplinary team(MDT)cooperation.Appropriate dosaging and identification of novel predictive targets should be considered in order to reduce the incidence and severity of ILICI in the future.Meanwhile,further basic research is required to elucidate the potential pathophysiological mechanisms and risk factors of ILICI.With the refinement of evidence in clinical evidence-based medicine and deepening of basic research,the diagnosis and treatment level of ILICI will also be further improved.

Result Analysis
Print
Save
E-mail