1.Targeting TM4SF1 promotes tumor senescence enhancing CD8+ T cell cytotoxic function in hepatocellular carcinoma
Weifeng ZENG ; Furong LIU ; Yachong LIU ; Ze ZHANG ; Haofan HU ; Shangwu NING ; Hongwei ZHANG ; Xiaoping CHEN ; Zhibin LIAO ; Zhanguo ZHANG
Clinical and Molecular Hepatology 2025;31(2):489-508
Background/Aims:
Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated.
Methods:
TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection.
Results:
TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy.
Conclusions
Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.
2.Targeting TM4SF1 promotes tumor senescence enhancing CD8+ T cell cytotoxic function in hepatocellular carcinoma
Weifeng ZENG ; Furong LIU ; Yachong LIU ; Ze ZHANG ; Haofan HU ; Shangwu NING ; Hongwei ZHANG ; Xiaoping CHEN ; Zhibin LIAO ; Zhanguo ZHANG
Clinical and Molecular Hepatology 2025;31(2):489-508
Background/Aims:
Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated.
Methods:
TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection.
Results:
TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy.
Conclusions
Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.
3.Targeting TM4SF1 promotes tumor senescence enhancing CD8+ T cell cytotoxic function in hepatocellular carcinoma
Weifeng ZENG ; Furong LIU ; Yachong LIU ; Ze ZHANG ; Haofan HU ; Shangwu NING ; Hongwei ZHANG ; Xiaoping CHEN ; Zhibin LIAO ; Zhanguo ZHANG
Clinical and Molecular Hepatology 2025;31(2):489-508
Background/Aims:
Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) progression and senescence remains to be elucidated.
Methods:
TM4SF1 expression in HCC samples was evaluated using immunohistochemistry and flow cytometry. Cellular senescence was assessed through SA-β-gal activity assays and Western blot analysis. TM4SF1-related protein interactions were investigated using immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence. Tumor-infiltrating immune cells were analyzed by flow cytometry. The HCC mouse model was established via hydrodynamic tail vein injection.
Results:
TM4SF1 was highly expressed in human HCC samples and murine models. Knockdown of TM4SF1 suppressed HCC proliferation both in vitro and in vivo, inducing non-secretory senescence through upregulation of p16 and p21. TM4SF1 enhanced the interaction between AKT1 and PDPK1, thereby promoting AKT phosphorylation, which subsequently downregulated p16 and p21. Meanwhile, TM4SF1-mediated AKT phosphorylation enhanced PD-L1 expression while reducing major histocompatibility complex class I level on tumor cells, leading to impaired cytotoxic function of CD8+ T cells and an increased proportion of exhausted CD8+ T cells. In clinical HCC samples, elevated TM4SF1 expression was associated with resistance to anti-PD-1 immunotherapy. Targeting TM4SF1 via adeno-associated virus induced tumor senescence, reduced tumor burden and synergistically enhanced the efficacy of anti-PD-1 therapy.
Conclusions
Our results revealed that TM4SF1 regulated tumor cell senescence and immune evasion through the AKT pathway, highlighting its potential as a therapeutic target in HCC, particularly in combination with first-line immunotherapy.
4.Giant pleomorphic adenoma of the tubal torus: a case report and literature review.
Yinglin YANG ; Xiaoping WU ; Wanting ZENG ; Jichuan CHEN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(7):670-673
Pleomorphic adenoma arising from the torus tubarius of the nasopharynx is an extremely rare entity with limited epidemiological data and unclear etiological mechanisms. Its pathogenesis may be related to the eustachian tube salivary glands. Here we report an elderly female patient with a long history of snoring, hypernasal speech and epistaxis. Following comprehensive diagnostic evaluation, the patient underwent tumor resection under nasal endoscopy. There were no postoperative complications, the symptoms were significantly improved, and there was no obvious recurrence during the follow-up. We summarized the experience of diagnosis and treatment of giant pleomorphic adenoma of the tubal torus. The main treatment for tubal torus pleomorphic adenoma is complete surgical resection, with a good prognosis and a low recurrence rate.
Humans
;
Female
;
Adenoma, Pleomorphic/surgery*
;
Aged
;
Nasopharynx/pathology*
5.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
6.Health education needs of patients undergoing fecal microbiota transplantation at different stages: a qualitative study
Sining ZENG ; Ling XU ; Zining GUO ; Shufan CHEN ; Keyu LING ; Haihan LI ; Xiaoping ZHU
Chinese Journal of Modern Nursing 2025;31(7):868-874
Objective:To explore the health education needs of patients undergoing fecal microbiota transplantation (FMT) at different stages of treatment.Methods:A qualitative research method was employed and an interview guide based on timing theory was developed. Semi-structured interviews were conducted with patients treated for colorectal conditions with FMT at Tenth People's Hospital of Tongji University from August to October 2022. Data from the interviews were analyzed using thematic analysis.Results:A total of 19 patients aged 20 to 65 were interviewed, including seven males and 12 females. A total of five main themes and 15 subthemes were identified: health education demands during the diagnosis phase (basic information about FMT; knowledge about donor screening), health education demands during the preparation phase (alleviating discomfort caused by nasoenteric tubes; interpretation of examination reports), health education demands during the execution phase (dietary guidance during FMT; exercise guidance during FMT; medication and supplementary training guidance; management of adverse reactions), health education demands during the adaptation phase (consolidating treatment effects; knowledge related to FMT capsules; post-discharge follow-up content and methods; post-discharge precautions), long-term health education demands (diverse health education tools; individualized health education approaches; alleviating psychological anxiety) .Conclusions:Patients undergoing FMT have numerous concerns, and diverse health education needs throughout the treatment process. Healthcare professionals should adopt various health education strategies to address these needs.
7.Health education needs of patients undergoing fecal microbiota transplantation at different stages: a qualitative study
Sining ZENG ; Ling XU ; Zining GUO ; Shufan CHEN ; Keyu LING ; Haihan LI ; Xiaoping ZHU
Chinese Journal of Modern Nursing 2025;31(7):868-874
Objective:To explore the health education needs of patients undergoing fecal microbiota transplantation (FMT) at different stages of treatment.Methods:A qualitative research method was employed and an interview guide based on timing theory was developed. Semi-structured interviews were conducted with patients treated for colorectal conditions with FMT at Tenth People's Hospital of Tongji University from August to October 2022. Data from the interviews were analyzed using thematic analysis.Results:A total of 19 patients aged 20 to 65 were interviewed, including seven males and 12 females. A total of five main themes and 15 subthemes were identified: health education demands during the diagnosis phase (basic information about FMT; knowledge about donor screening), health education demands during the preparation phase (alleviating discomfort caused by nasoenteric tubes; interpretation of examination reports), health education demands during the execution phase (dietary guidance during FMT; exercise guidance during FMT; medication and supplementary training guidance; management of adverse reactions), health education demands during the adaptation phase (consolidating treatment effects; knowledge related to FMT capsules; post-discharge follow-up content and methods; post-discharge precautions), long-term health education demands (diverse health education tools; individualized health education approaches; alleviating psychological anxiety) .Conclusions:Patients undergoing FMT have numerous concerns, and diverse health education needs throughout the treatment process. Healthcare professionals should adopt various health education strategies to address these needs.
8.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
9.Dilemmas in decision-making:a qualitative study of family surrogate decision-makers of severe stroke patients
Zining GUO ; Keyu LING ; Shufan CHEN ; Haihan LI ; Ting YAO ; Sining ZENG ; Ling XU ; Xiaoping ZHU
Chinese Journal of Nursing 2024;59(14):1746-1751
Objective To explore the dilemmas faced by surrogate decision-makers of severe stroke patients in treatment decision-making,and to provide a basis for developing decision support strategies.Methods From April to December 2023,through phenomenological qualitative research with 16 surrogate decision-makers with severe stroke patients from ICU of the department of neurology in a tertiary hospital in Jing'an District,Shanghai.semi-structured in-depth interviews were used to examine the perceptions of decision-making on surrogate.Data were analyzed via Braun's style of thematic analysis.Results 4 themes and 10 sub-themes were identified.Theme 1:negative emotional dilemmas(urgent decision-making leads to anxiety,fear,and unknown stroke trajectory increases the sense of uncertainty).Theme 2:supportive environment dilemmas(lack of information support delays decision-making;lack of family support increases decision-making stress;insufficient economic support increases the burden of decision-making).Theme 3:the dilemma of weighing the pros and cons(difficult trade-offs between risk and reward,tough decisions between reality and ethics,conflicting choices of life and dignity).Theme 4:preference management dilemmas(practical difficulties in adhering to patient preferences,impediments to decision-making due to unknown patient preferences).Conclusion Surrogate decision-makers of severe stroke patients face multiple decision-making dilemmas.Healthcare professionals should provide emotional support in multiple ways and comprehensive support to reduce the decision-making dilemmas experienced by surrogate decision-makers,as well as implement death education for surrogate decision-makers and promote advance care planning to reduce their decision-making stress.
10.Diagnostic value of serum soluble CD40 ligand in gestational diabetes mellitus
China Modern Doctor 2024;62(25):26-29
Objective To investigate the value of serum soluble CD40 ligand(sCD40L)for gestational diabetes mellitus(GDM)and adverse pregnancy outcomes.Methods A total of 100 pregnant women with GDM who received regular prenatal check-up and delivered in Zhongshan Torch Development Zone People's Hospital from January to December 2023 were included in GDM group,and 50 pregnant women with normal blood glucose levels who received regular prenatal check-up and delivered in the hospital during the same period were included in normal control group.Clinical data of two groups were collected and pregnancy outcomes were followed up.Receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of sCD40L in GDM,and multifactor Logistic regression model was used to explore the risk factors of GDM.Results Serum sCD40L levels in GDM group were significantly higher than those in normal control group at different time points during pregnancy(P<0.05).ROC curve showed that the best cutoff values of serum sCD40L level in the first and second trimesters in assisting the diagnosis of GDM were 0.975ng/ml and 1.195ng/ml,the area under the curve was 0.812 and 0.878,and the sensitivity was 73.08%and 78.43%,the specificity was 78.05%and 80.00%,respectively.Multivariate Logistic regression showed that age 30-39 years old,family history of diabetes mellitus,higher fasting blood glucose in first trimester,higher sCD40L in first trimester and second trimester were all independent risk factors for GDM(P<0.05).The levels of serum sCD40L in the first,second and third trimesters of GDM women with adverse pregnancy outcome were significantly higher than those in GDM women with normal pregnancy outcome(P<0.05).Conclusion Serum sCD40L levels are abnormally increased in pregnant women with GDM and adverse pregnancy outcomes,and serum sCD40L levels in first and second trimesters may have early warning value for GDM.

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