1.Post-exposure prophylaxis and follow-up in children and young persons presenting with sexual assault.
Sarah Hui Wen YAO ; Karen NADUA ; Chia Yin CHONG ; Koh Cheng THOON ; Chee Fu YUNG ; Natalie Woon Hui TAN ; Kai-Qian KAM ; Peter WONG ; Juliet TAN ; Jiahui LI
Annals of the Academy of Medicine, Singapore 2025;54(7):410-418
INTRODUCTION:
Paediatric sexual assault (SA) victims should be assessed for post-exposure prophylaxis (PEP) to mitigate the risk of sexually transmitted infections (STIs). We describe the clinical characteristics of children and young persons (CYPs) presenting with SA at KK Women's and Children's Hospital in Singapore, viral PEP (human immunodeficiency virus [HIV] and hepatitis B virus [HBV]) prescribing practices, and STI evaluation at follow-up.
METHOD:
Medical records of CYPs ≤16 years who presented with SA between January 2022 and August 2023 were reviewed, including assault and assailant characteristics, baseline and follow-up STI screening, PEP prescription, adherence and follow-up attendance. CYPs with SA in the preceding 72 hours by HIV-positive or HIV-status unknown assailants with high-risk characteris-tics were eligible for HIV PEP.
RESULTS:
We analysed 278 CYPs who made 292 SA visits. There were 40 (13.7%) CYPs eligible for HIV PEP, of whom 29 (82.9%) received it. Among those tested at baseline, 9% and 34.9% of CYPs tested positive for Chlamydia trachomatis and Gardnerella vaginalis, respectively. None tested positive for Neisseria gonorrhoeae, Trichomonas vaginalis, HIV, HBV or hepatitis C. Majority of CYPs tested were HBV non-immune (n=167, 67.6%); only 77 (46.1%) received the vaccine. Out of 27 CYPs eligible for HBV PEP with immunoglobulin, only 21 (77.7%) received immunoglobulin. A total of 37 CYPs received HIV PEP, including 8 who were retrospectively deemed ineligible. Only 10 (27%) completed the course. Overall, 153 (57.7%) CYPs attended follow-up, and none seroconverted for HIV or HBV.
CONCLUSION
We report suboptimal rates of HBV post-exposure vaccination, and low compliance to HIV PEP and follow-up among paediatric SA victims. Factors contri-buting to poor compliance should be examined to optimise care for this vulnerable population.
Humans
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Post-Exposure Prophylaxis/methods*
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Female
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Child
;
Adolescent
;
Singapore/epidemiology*
;
HIV Infections/prevention & control*
;
Male
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Sexually Transmitted Diseases/epidemiology*
;
Retrospective Studies
;
Hepatitis B/prevention & control*
;
Follow-Up Studies
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Child, Preschool
;
Sex Offenses/statistics & numerical data*
;
Child Abuse, Sexual
2.Role of Brg1 in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia model.
Ling GUAN ; Mao-Zhu XU ; Yao-Zheng LING ; Li-Li YANG ; Ling-Huan ZHANG ; Sha LIU ; Wen-Jing ZOU ; Zhou FU
Chinese Journal of Contemporary Pediatrics 2025;27(6):731-739
OBJECTIVES:
To investigate the role and mechanism of Brahma-related gene 1 (Brg1) in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia (BPD) model.
METHODS:
Wild-type C57BL/6 and Brg1f1/f1 mice were randomly divided into four groups: wild-type control, wild-type BPD, Brg1f1/f1 control, and Brg1f1/f1 BPD (n=5 each). Immortalized mouse pulmonary alveolar type 2 cells (imPAC2) were cultured, and Brg1 gene was knocked down using lentivirus transfection technology. Cells were divided into three groups: control, empty vector, and Brg1 knockdown. Hematoxylin and eosin staining and immunofluorescence were used to detect pathological changes in mouse lung tissue. Western blot and real-time fluorescent quantitative PCR were used to measure Brg1 protein and mRNA expression levels in mouse lung tissue. Western blot and immunofluorescence were used to detect the expression of homeodomain-containing protein homeobox (HOPX), surfactant protein C (SPC), and Wnt/β-catenin signaling pathway proteins in mouse lung tissue and imPAC2 cells. The CCK8 assay was used to assess the proliferation of imPAC2 cells, and co-immunoprecipitation was performed to verify the interaction between Brg1 and β-catenin proteins in imPAC2 cells.
RESULTS:
Compared to the Brg1f1/f1 control group and wild-type BPD group, the Brg1f1/f1 BPD group showed increased alveolar diameter and SPC protein expression, and decreased relative density of pulmonary vasculature and HOPX protein expression (P<0.05). Compared to the control group, the Brg1 knockdown group showed increased cell proliferation ability, protein expression levels of SPC, Wnt5a and β-catenin, and β-catenin protein fluorescence intensity, along with decreased HOPX protein expression (P<0.05). An interaction between Brg1 and β-catenin proteins was confirmed.
CONCLUSIONS
The Brg1 gene may promote the proliferation of alveolar type 2 epithelial cells by regulating the Wnt/β-catenin signaling pathway, thus influencing the occurrence and development of BPD.
Animals
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DNA Helicases/genetics*
;
Transcription Factors/genetics*
;
Wnt Signaling Pathway/physiology*
;
Nuclear Proteins/genetics*
;
Mice
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Bronchopulmonary Dysplasia/etiology*
;
Mice, Inbred C57BL
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beta Catenin/physiology*
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Disease Models, Animal
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Cell Proliferation
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Lung/pathology*
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Male
3.Characteristics of T cell immune responses in adults inoculated with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months
Jing WANG ; Ya-Qun LI ; Hai-Yan WANG ; Yao-Ru SONG ; Jing LI ; Wen-Xin WANG ; Lin-Yu WAN ; Chun-Bao ZHOU ; Xing FAN ; Fu-Sheng WANG
Medical Journal of Chinese People's Liberation Army 2024;49(2):165-170
Objective To evaluate the characteristics of different antigen-specific T cell immune responses to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)after inoculation with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months.Methods Fifteen healthy adults were enrolled in this study and blood samples collected at 12 months after receiving two doses of SARS-CoV-2 inactivated vaccine.The level and phenotypic characteristics of SARS-CoV-2 antigen-specific T lymphocytes were detected by activation-induced markers(AIM)based on polychromatic flow cytometry.Results After 12 months of inoculation with 2 doses of SARS-CoV-2 inactivated vaccine,more than 90%of adults had detectable Spike and Non-spike antigen-specific CD4+ T cells immune responses(Spike:14/15,P=0.0001;Non-spike:15/15,P<0.0001).80%of adults had detectable Spike and Non-spike antigen-specific CD8+ T cells immune responses(Spike:12/15,P=0.0463;Non-spike:12/15,P=0.0806).Antigen-specific CD4+ T cells induced by SARS-CoV-2 inactivated vaccination after 12 months were composed of predominantly central memory(CM)and effector memory 1(EM1)cells.On the other hand,in terms of helper subsets,antigen-specific CD4+ T cells mainly showed T helper 1/17(Th1/17)and T helper 2(Th2)phenotypes.Conclusions SARS-CoV-2 inactivated vaccination generates durable and extensive antigen-specific CD4+ T cell memory responses,which may be the key factor for the low proportion of severe coronavirus disease 2019(COVID-19)infection in China.
4.Element profiles of benzoapyrene malignantly transformed 16HBE cells and joint effects of copper with cisplatin or vinorelbine on cell proliferation
Yu WANG ; Lailai YAN ; Juanling FU ; Mingmei HAO ; Wen CHEN ; Biyun YAO ; Bing CHANG ; Peng ZHAO
Chinese Journal of Pharmacology and Toxicology 2024;38(1):1-10
OBJECTIVE To assess the profiles of elements in benzo[a]pyrene(BaP)induced carci-nogenesis,and explore the joint effects of copper with cisplatin or vinorelbine on cell proliferation.METHODS Forty-four elements were measured using an inductively coupled plasma mass spectrometer in 16HBE cells and BaP malignantly transformed 16HBE(T-16HBE-C1)cells.Partial least square was used to validate the robustness of cell classification of elements.Cell viability was measured by MTT assay for copper(0,237,340,487,1000 and 1432 μmol·L-1),cisplatin(0,4.4,6.1,8.6,12.0 and 16.8 μmol·L-1),and vinorelbine(0,3.8,9.8,25.0,40.0 and 64.0 μmol·L-1)to acquire their half maximal inhibitory concentra-tion(IC50).Mixtures of copper and chemotherapeutics were prepared according to the ratio of each IC50.Their joint effects on cell viability were assessed by MTT assay and isobolographic analysis.Inhibition effect of copper(0,50,100,200,400 and 800 μmol·L-1)with IC50 of cisplatin or vinorelbine on prolifera-tion of T-16HBE-C1 cells was also assessed.RESULTS A total of 29 elements were quantified in 16HBE and T-16HBE-C1 cells,among which concentrations of copper,zinc,silver,selenium and rubidium decreased(P<0.05,P<0.01),while those of molybdenum,arsenic,lithium,germanium,strontium,nickel,lanthanum,mercury,iron,and cesium increased(P<0.05,P<0.01)in T-16HBE-C1 cells.Element concen-tration could be used to distinguish T-16HBE-C1 cells from 16HBE cells.Copper concentration-dependently inhibited proliferation of both cells,with a statistically significant lower IC50 of(613±16)μmol·L-1 in 16HBE cells than(776±15)μmol·L-1 in T-16HBE-C1 cells(P<0.01).Mixtures of copper and cisplatin(1∶69.5)or vinorelbine(1∶33.4)could inhibit cell proliferation,and copper had additive effects with cisplatin or vinorelbine.When copper concentration was higher than 400 μmol·L-1,copper combined with IC50 of cisplatin or vinorelbine inhibited cell proliferation of T-16HBE-C1 cells compared with IC50 of cisplatin(11.2 μmol·L-1)or vinorelbine(23.2 μmol·L-1)alone.CONCLUSION Element profiles and correlations can change significantly after 16HBE cells are malignantly transformed by BaP.Copper could inhibit the proliferation of T-16HBE-C1 cells and have additive effects with cisplatin or vinorelbine in higher concentration.
5.Experts consensus on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)
Min HU ; Chi YANG ; Huawei LIU ; Haixia LU ; Chen YAO ; Qiufei XIE ; Yongjin CHEN ; Kaiyuan FU ; Bing FANG ; Songsong ZHU ; Qing ZHOU ; Zhiye CHEN ; Yaomin ZHU ; Qingbin ZHANG ; Ying YAN ; Xing LONG ; Zhiyong LI ; Yehua GAN ; Shibin YU ; Yuxing BAI ; Yi ZHANG ; Yanyi WANG ; Jie LEI ; Yong CHENG ; Changkui LIU ; Ye CAO ; Dongmei HE ; Ning WEN ; Shanyong ZHANG ; Minjie CHEN ; Guoliang JIAO ; Xinhua LIU ; Hua JIANG ; Yang HE ; Pei SHEN ; Haitao HUANG ; Yongfeng LI ; Jisi ZHENG ; Jing GUO ; Lisheng ZHAO ; Laiqing XU
Chinese Journal of Stomatology 2024;59(10):977-987
Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.
6.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
7.Effect of Shugan Tiaoshen acupuncture combined with western medication on depression-insomnia comorbidity due to COVID-19 quarantine: a multi-central randomized controlled trial.
Lu-da YAN ; Zhong-Xian LI ; Yu ZHANG ; Xue-Song LIANG ; Jing-Jing LI ; Miao WU ; Guo-Ao SHI ; Rui-Ming CHEN ; Xiang JI ; Si-Yao ZUO ; Shi-Yun CHEN ; Peng ZHOU ; Wen-Bin FU
Chinese Acupuncture & Moxibustion 2023;43(3):255-260
OBJECTIVE:
To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability.
METHODS:
Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24+), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO15), Gan (CO12) and Shen (CO10). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups.
RESULTS:
After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05).
CONCLUSION
Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.
Humans
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Depression
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Quarantine
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Serotonin
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Sleep Initiation and Maintenance Disorders
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COVID-19
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Acupuncture Therapy
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Comorbidity
8.Hepatocellular carcinoma segmentation and pathological differentiation degree prediction method based on multi-task learning.
Han WEN ; Ying ZHAO ; Yong YANG ; Hongkai WANG ; Ailian LIU ; Yu YAO ; Zhongliang FU
Journal of Biomedical Engineering 2023;40(1):60-69
Hepatocellular carcinoma (HCC) is the most common liver malignancy, where HCC segmentation and prediction of the degree of pathological differentiation are two important tasks in surgical treatment and prognosis evaluation. Existing methods usually solve these two problems independently without considering the correlation of the two tasks. In this paper, we propose a multi-task learning model that aims to accomplish the segmentation task and classification task simultaneously. The model consists of a segmentation subnet and a classification subnet. A multi-scale feature fusion method is proposed in the classification subnet to improve the classification accuracy, and a boundary-aware attention is designed in the segmentation subnet to solve the problem of tumor over-segmentation. A dynamic weighted average multi-task loss is used to make the model achieve optimal performance in both tasks simultaneously. The experimental results of this method on 295 HCC patients are superior to other multi-task learning methods, with a Dice similarity coefficient (Dice) of (83.9 ± 0.88)% on the segmentation task, while the average recall is (86.08 ± 0.83)% and an F1 score is (80.05 ± 1.7)% on the classification task. The results show that the multi-task learning method proposed in this paper can perform the classification task and segmentation task well at the same time, which can provide theoretical reference for clinical diagnosis and treatment of HCC patients.
Humans
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Carcinoma, Hepatocellular
;
Liver Neoplasms
;
Learning
9.Invasive mucinous adenocarcinoma of the lungs versus mixed invasive mucinous and non-mucinous adenocarcinoma:a clinicopathological analysis
Shuangshuang PENG ; Wei LI ; Zhaoya ZHOU ; Biao ZHANG ; Chaoshan WANG ; Xiaohong PU ; Wen YANG ; Jun YANG ; Hongyan WU ; Yao FU ; Jieyu CHEN ; Xiangshan FAN
Chinese Journal of Clinical and Experimental Pathology 2023;39(11):1328-1333
Purpose To investigate the clinicopathological characteristics,diagnosis,and differential diagnosis of invasive mucinous adenocarcinoma(IMA)and mixed invasive mucinous and non-mucinous adenocarcinoma(mIMA).Methods The clinical data were collected in 36 patients with primary IMA and 17 patients with mIMA,and the expression of TTF-1,CK7,CK20,SATB2,CDX2,EGFR,HNF4a,etc.was detected by immunohistochemical EnVision two-step method.The Sanger se-quencing and the FISH were used for KRAS mutation and NRG1 gene rearrangement detection.The clinicopathological character-istics were analyzed with review of relevant literature.Results There were 9 cases(25.0%)and 3(8.3%)cases of papillary and micropapillary structures in IMA,while 13 cases(76.5%)(P<0.001)and 9 cases(52.9%)(P=0.001)were present in mIMA.There were 5 cases(13.9%)of high nuclear grade of IMA and 10 cases(58.8%)of high nuclear grade of mIMA(P=0.002).TTF-1 had a positive rate of 37.5%in IMA,but 60.0%and 80.0%in the mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA(P=0.021),respectively.The positive rates of CK7,CK20,and CDX2 in IMA were 90.6%,21.9%,and 9.4%,and the positive rates in mucinous adenocarcinoma and non-mucinous adenocarcinoma components of mIMA were 100%,20%,20%and 100%,6.7%,6.7%,respectively and no SATB2 expression was found in all cases.There was no significant difference in the expres-sion of total EGFR and two EGFR mutation-specific antibodies(L858R,DEL19)between IMA and mIMA.There were 3 cases of mucinous adenocarcinoma with L858R positive in mIMA,and 2 of them were negative for non-mueinous adenocarcinoma.In another case,the non-mueinous adenocarcinoma component of mIMA expressed DEL19,but the mucinous adenocarcinoma component was not expressed.The positive rate of HNF4a in IMA was 72.0%(18/25),and those of HNF4a in mucinous adenocarcinoma and non-mucinous adenocarcinoma in mIMA were 41.7%(5/12)and 33.3%(4/12),respectively(P=0.048).KRAS gene sequencing was carried out in 19 cases of IMA,among which 9 cases(47.4%)had mutations,G12D and G12V were most commonly detected,and 4 cases of mIMA were sequenced,but none of them showed KRAS mutations.FISH detection showed that 2 cases(7.1%)IMAs had NRG1 translocation rearrangement.Conclusion Pulmonary mIMA is more aggressive than IMA.For example,mIMA has significantly more papillary structure,micropapillary structure,and high nu-clear grade cases than IMA.The differences in immunohisto-chemical expression and KRAS mutation between the two are sta-tistically significant.
10.Clinical Significance of High Expression of Endoplasmic Reticulum Stress-related Proteins Glucose-regulating Protein 78 and X-box Binding Protein 1 induced by Fusobacterium Nucleatum in Esophageal Squamous Cell Carcinoma
Si-mo CHEN ; Zhe-yuan ZHANG ; Jia-hao ZHANG ; Ke-yao HE ; Yi-wen LIU ; Fu-you ZHOU
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(3):403-415
ObjectiveTo analyze the induction effect of Fusobacterium nucleatum (Fn) on endoplasmic reticulum stress-related proteins Glucose-regulating protein 78(GRP78) and X-box binding protein 1(XBP1) in esophageal squamous cell carcinoma (ESCC), and to explore its potential mechanism and clinical significance. MethodsESCC cells KYSE150 and KYSE140 were infected with Fn for 12 h, 24 h and 48 h. The oxidative stress indexes (ROS, MDA and SOD) and the expression of GRP78 and XBP1 in each group were detected by oxidative stress index kit and Western blot. The experiment was divided into Fn groups, Fn+siNC1 groups, Fn+siGRP78 groups, Fn+siNC2 groups and Fn+siXBP1 groups; the oxidative stress indexes, paclitaxel (PTX) response efficacy, abilities of proliferation, invasion and metastasis in each group were compared. The infection of Fn and the expression of GRP78 and XBP1 in 234 ESCC and paracancerous tissues were detected by RNA scope and immunohistochemistry. The correlation between each factor and clinicopathological characteristics of patients was analyzed by Chi-square test. The influence of each factor on the survival of patients was compared by Kaplan-meier survival estimate. ResultsCompared with Fn uninfected KYSE150 and KYSE140 cells, the content of ROS and MDA was gradually increased, the activity of SOD was gradually decreased, and the expression of GRP78 and XBP1 was gradually increased in Fn infected groups (12 h, 24 h and 48 h) (P < 0.05). Compared with Fn groups, Fn+siNC1 groups, and Fn+siNC2 groups, ROS and MDA contents were decreased, SOD activity was increased, PTX response efficacy was enhanced, and abilities of proliferation, invasion and metastasis were decreased in Fn+siGRP78 and Fn+siXBP1 groups (P < 0.05). The rates of Fn, GRP78 and XBP1 in ESCC tissues were 43.16%, 69.66% and 60.68%, respectively. And the three indexes were significantly consistent (P < 0.05). The patients with positive Fn infection and high expression of GRP78 and XBP1 were mostly males with a history of smoking and drinking, and the tumor differentiation degree was low, the invasion degree was deep, the lymph node metastasis rate was high, and the clinical stage was mostly stage Ⅲ/Ⅳ. The 5-year survival time of patients with above positive indexes was shortened (P < 0.05). ConclusionsFn could induce endoplasmic reticulum stress by inducing the high expression of GRP78 and XBP1, and promote the malignant evolution of ESCC.

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