1.Cytokeratin (pan)-positive EWSR1/FUS::CREB fusion malignant tumor in abdominopelvic cavity: a clinicopathological and molecular analysis of four cases
Fenglin ZANG ; Yong WANG ; Xiyin WEI ; Yalei WANG ; Ye LUO ; Yuhong GUO ; Tingting DING
Chinese Journal of Pathology 2025;54(6):626-631
Objective:To investigate the clinicopathological and molecular genetic characteristics of pan cytokeratin (CKpan)-positive EWSR1/FUS::CREB fusion malignant tumors in abdominopelvic cavity.Methods:Four cases of malignant tumor with CKpan-positive EWSR1/FUS::CREB fusion were selected from January 2019 to July 2024 in the Department of Pathology, Tianjin Medical University Cancer Hospital, Tianjin, China. Their clinical, pathological, and immunohistochemical characteristics were examined. Their molecular genetic characteristics were analyzed using fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS).Results:Among the 4 patients, there were 2 males and 2 females, aged 44, 44, 48 and 66 years, respectively. The tumor sites included 1 case located between the stomach and transverse colon, 1 case on the serous surface of the gastric wall, 1 case in the transverse mesocolon, and 1 case in transverse mesocolon and small mesentery. The clinical manifestations were mostly abdominal distension and abdominal pain. The maximum diameter of the tumor in the surgical resection specimen was 3.5-8.5 cm. The tumor′s cut surface was grayish-white and gray-yellow in color, with medium consistency. Microscopically, the tumor cells were mainly composed of epithelioid tumor cells, and 2 of the tumors showed that tumor cells arranged in a solid sheet or multinodular pattern, and the cytoplasm of the tumor cells was abundant, lightly stained, and the boundaries were unclear, accompanied by the formation of capsules or microcapsules, and lymphocyte and plasma cell sleeves were seen. In one case, the pseudopapillary arrangement was present, and the tumor cells were radially distributed around the fibrovascular axis. In another case, it was arranged in a pseudoacinar pattern, and the nest was surrounded by slender reticular fibers. Immunohistochemistry showed that tumor cells expressed CKpan (4/4) and WT1 (4/4, including 1 focal positive). Vimentin, CK8/18, D2-40 and S-100 were expressed in various intensities, while Calretinin was locally positive or negative. FISH showed that 2 cases had EWSR1 break-apart and 2 cases had FUS break-apart. NGS confirmed the presence of EWSR1::CREM fusion (1 case) and FUS::CREM fusion (2 cases), respectively. Except for 1 recently diagnosed case, 3 cases were followed up: 1 patient died due to tumor recurrence and metastasis (overall survival was 33 months), and 2 patients survived (1 case had recurrence 58 months after surgery, and 1 case had no recurrence or metastasis after surgery).Conclusions:CKpan-positive EWSR1/FUS::CREB fusion malignant tumor is a rare malignancy tumor with undetermined classification that tends to occur in the abdominopelvic cavity and often involves the gastrointestinal tract. Molecular testing such as FISH and NGS is helpful for a definitive diagnosis.
2.Low-level laser therapy for the treatment of male infertility and erectile dysfunction
Yuanjie NIU ; Zhongcheng XIN ; Guiting LIN ; Pan DING ; Jiancheng PAN ; Yuhong FENG ; Yinglu GUO
Journal of Peking University(Health Sciences) 2025;57(4):627-632
Low-level laser therapy(LLLT),a noninvasive photobiomodulation technique,employs red or near-infrared(NIR)light(600-1 000 nm)with power outputs ranging from 5 to 500 mW.It exerts therapeutic effects through molecular mechanisms,specifically the activation of cytochrome C oxidase(CCO)and the modulation of intracellular signaling pathways.By enhancing mitochondrial adenosine triphosphate(ATP)synthesis,LLLT mitigates oxidative stress,regulates the reactive oxygen species(ROS)/glutathione peroxidase(GSH-Px)/superoxide dismutase(SOD)axis,and activates key path-ways,including phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)and mitogen-activated pro-tein kinase/extracellular signal-regulated kinase(MAPK/ERK).These mechanisms confer antioxidant,anti-inflammatory,and pro-regenerative properties to LLLT,making it a viable intervention for dermato-logical conditions,oncological therapies,and musculoskeletal disorders.Recent preclinical studies un-derscore LLLT's potential in male reproductive health.Specifically,it ameliorates cavernosal fibrosis and endothelial dysfunction in erectile dysfunction(ED)models by upregulating the PI3K/Akt and MAPK/ERK pathways.In the context of sperm biology,LLLT enhances motility and acrosomal integrity in both fresh and cryopreserved spermatozoa.This is achieved through mitochondrial metabolic reprogramming,such as CCO-mediated electron transport chain activation,redox homeostasis restoration,and epigenetic modulation involving DNA methylation and histone acetylation.Additionally,LLLT alleviates scrotal heat-induced oligospermia by promoting seminiferous epithelial differentiation,elevating serum testoster-one levels,and suppressing lipid peroxidation.These findings highlight the translational potential of LLLT in regenerative medicine,particularly for male sexual and reproductive disorders.Future research efforts should focus on interdisciplinary collaborations spanning life sciences,engineering,and physics.The goal is to optimize laser parameters,including wavelength,irradiance,and treatment duration,and establish standardized protocols.Rigorous preclinical and clinical investigations are paramount to validate the safety,efficacy,and long-term outcomes of LLLT,ultimately paving the way for its integration into precision medicine frameworks for urological and reproductive therapies.
3.Efficacy and safety of dye-free submucosal injection solution for gastric endoscopic submucosal dissection
Wan LU ; Yonggang DING ; Ting ZHANG ; Lijuan MAO ; Jing CHEN ; Yuhong ZHOU ; Jun XIAO ; Wenjie LI ; Yaohui WANG ; Qide ZHANG
Chinese Journal of Digestive Endoscopy 2025;42(10):823-827
To evaluate the efficacy and safety of dye-free submucosal injection solution for gastric endoscopic submucosal dissection (ESD), a retrospective cohort study was performed on data of inpatients with early gastric cancer and precancerous lesions who underwent ESD at the Digestive Endoscopy Center of Jiangsu Province Hospital of Traditional Chinese Medicine from January to December 2020. Cases were divided into dye-free submucosal injection solution group (the observation group) and dye-containing solution group (the control group). A total of 108 cases met the eligibility criteria for analysis (39 VS 69). Baseline characteristics were comparable between the two groups ( P>0.05). Compared with the control group, the observation group showed similar median procedure time (30.5 min VS 35.0 min), median dissection speed (0.3 cm2/min VS 0.4 cm2/min), mean volume of injection solution used (39.2 mL VS 38.8 mL), en bloc resection rate [100.0% (39/39) VS 98.6% (68/69)], and curative resection rate [97.4% (38/39) VS 97.1% (67/69)] (all P>0.05). Postoperative stay was 3.0±0.8 days in the observation group and 3.2±0.8 days in the control group ( t=-0.908, P=0.378). Delayed bleeding occurred in 3 (7.7%) patients VS 2 (2.9%) patients ( P=0.349), and postoperative infection occurred in 3 (7.7%) patients VS 8 (11.6%) patients ( P=0.743), respectively. In gastric ESD, dye-free submucosal injection solution demonstrates efficacy comparable with dye-containing solution and does not appreciably increase the incidence of intraoperative or postoperative complications.
4.Screening and validation of key genes for ferroptosis in doxorubicin-induced cardiomyopathy on machine learning
Xiaoying ZENG ; Xi ZHU ; Mengting DENG ; Zhiqiang DING ; Hongcheng FANG ; Yuhong DOU
Journal of China Medical University 2025;54(1):38-43
Objective To explore the role of ferroptosis in DIC through bioinformatics analysis of hub genes involved in ferroptosis in doxorubicin-induced cardiomyopathy(DIC),combined with in vitro experimental validation.Methods Divalent iron fluorescence staining confirms the occurrence of ferroptosis in myocardial cells of DIC.The GSE207737 dataset was retrieved from the Gene Expression Comprehensive Database(GEO)and intersected with the FerrDb database to identify ferroptosis-related genes.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the intersected genes and intersecting the genes obtained from LASSO regression analysis and SVM-SFR machine learning methods were used to obtain ferroptosis hub genes for DIC.Real-time PCR was used to validate H9C2 cells in the control and DIC model groups,and Western blotting was used to further validate those whose bioinformatics and real-time PCR results that did not match.Results Thirty-eight ferroptosis-related genes in DIC were identified,and GO and KEGG analyses showed that these genes mainly participate in cell metabolism.Five hub genes for ferroptosis in DIC were obtained using machine learning methods:Mpc1,Prdx1,Kdm4a,Alox 12b,and Tfrc.Through in vitro experiments,the mRNA expression levels of Mpc1,Prdx1,and Kdm4a were downregulated in the DIC model group compared to those in the control group(P<0.001),whereas the mRNA expression level of Alox12b was upregulated(P<0.001).There were no significant differences in the mRNA or protein expression levels of Tfrc(P>0.05).Conclusion Mpc1,Prdx1,Kdm4a,and Alox12b are key genes involved in ferroptosis in doxorubicin-induced cardiomyopathy and potential targets for the prevention and treatment of doxorubicin-induced cardiomyopathy in ferroptosis.
5.Low-level laser therapy for the treatment of male infertility and erectile dysfunction
Yuanjie NIU ; Zhongcheng XIN ; Guiting LIN ; Pan DING ; Jiancheng PAN ; Yuhong FENG ; Yinglu GUO
Journal of Peking University(Health Sciences) 2025;57(4):627-632
Low-level laser therapy(LLLT),a noninvasive photobiomodulation technique,employs red or near-infrared(NIR)light(600-1 000 nm)with power outputs ranging from 5 to 500 mW.It exerts therapeutic effects through molecular mechanisms,specifically the activation of cytochrome C oxidase(CCO)and the modulation of intracellular signaling pathways.By enhancing mitochondrial adenosine triphosphate(ATP)synthesis,LLLT mitigates oxidative stress,regulates the reactive oxygen species(ROS)/glutathione peroxidase(GSH-Px)/superoxide dismutase(SOD)axis,and activates key path-ways,including phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)and mitogen-activated pro-tein kinase/extracellular signal-regulated kinase(MAPK/ERK).These mechanisms confer antioxidant,anti-inflammatory,and pro-regenerative properties to LLLT,making it a viable intervention for dermato-logical conditions,oncological therapies,and musculoskeletal disorders.Recent preclinical studies un-derscore LLLT's potential in male reproductive health.Specifically,it ameliorates cavernosal fibrosis and endothelial dysfunction in erectile dysfunction(ED)models by upregulating the PI3K/Akt and MAPK/ERK pathways.In the context of sperm biology,LLLT enhances motility and acrosomal integrity in both fresh and cryopreserved spermatozoa.This is achieved through mitochondrial metabolic reprogramming,such as CCO-mediated electron transport chain activation,redox homeostasis restoration,and epigenetic modulation involving DNA methylation and histone acetylation.Additionally,LLLT alleviates scrotal heat-induced oligospermia by promoting seminiferous epithelial differentiation,elevating serum testoster-one levels,and suppressing lipid peroxidation.These findings highlight the translational potential of LLLT in regenerative medicine,particularly for male sexual and reproductive disorders.Future research efforts should focus on interdisciplinary collaborations spanning life sciences,engineering,and physics.The goal is to optimize laser parameters,including wavelength,irradiance,and treatment duration,and establish standardized protocols.Rigorous preclinical and clinical investigations are paramount to validate the safety,efficacy,and long-term outcomes of LLLT,ultimately paving the way for its integration into precision medicine frameworks for urological and reproductive therapies.
6.Screening and validation of key genes for ferroptosis in doxorubicin-induced cardiomyopathy on machine learning
Xiaoying ZENG ; Xi ZHU ; Mengting DENG ; Zhiqiang DING ; Hongcheng FANG ; Yuhong DOU
Journal of China Medical University 2025;54(1):38-43
Objective To explore the role of ferroptosis in DIC through bioinformatics analysis of hub genes involved in ferroptosis in doxorubicin-induced cardiomyopathy(DIC),combined with in vitro experimental validation.Methods Divalent iron fluorescence staining confirms the occurrence of ferroptosis in myocardial cells of DIC.The GSE207737 dataset was retrieved from the Gene Expression Comprehensive Database(GEO)and intersected with the FerrDb database to identify ferroptosis-related genes.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the intersected genes and intersecting the genes obtained from LASSO regression analysis and SVM-SFR machine learning methods were used to obtain ferroptosis hub genes for DIC.Real-time PCR was used to validate H9C2 cells in the control and DIC model groups,and Western blotting was used to further validate those whose bioinformatics and real-time PCR results that did not match.Results Thirty-eight ferroptosis-related genes in DIC were identified,and GO and KEGG analyses showed that these genes mainly participate in cell metabolism.Five hub genes for ferroptosis in DIC were obtained using machine learning methods:Mpc1,Prdx1,Kdm4a,Alox 12b,and Tfrc.Through in vitro experiments,the mRNA expression levels of Mpc1,Prdx1,and Kdm4a were downregulated in the DIC model group compared to those in the control group(P<0.001),whereas the mRNA expression level of Alox12b was upregulated(P<0.001).There were no significant differences in the mRNA or protein expression levels of Tfrc(P>0.05).Conclusion Mpc1,Prdx1,Kdm4a,and Alox12b are key genes involved in ferroptosis in doxorubicin-induced cardiomyopathy and potential targets for the prevention and treatment of doxorubicin-induced cardiomyopathy in ferroptosis.
7.Cytokeratin (pan)-positive EWSR1/FUS::CREB fusion malignant tumor in abdominopelvic cavity: a clinicopathological and molecular analysis of four cases
Fenglin ZANG ; Yong WANG ; Xiyin WEI ; Yalei WANG ; Ye LUO ; Yuhong GUO ; Tingting DING
Chinese Journal of Pathology 2025;54(6):626-631
Objective:To investigate the clinicopathological and molecular genetic characteristics of pan cytokeratin (CKpan)-positive EWSR1/FUS::CREB fusion malignant tumors in abdominopelvic cavity.Methods:Four cases of malignant tumor with CKpan-positive EWSR1/FUS::CREB fusion were selected from January 2019 to July 2024 in the Department of Pathology, Tianjin Medical University Cancer Hospital, Tianjin, China. Their clinical, pathological, and immunohistochemical characteristics were examined. Their molecular genetic characteristics were analyzed using fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS).Results:Among the 4 patients, there were 2 males and 2 females, aged 44, 44, 48 and 66 years, respectively. The tumor sites included 1 case located between the stomach and transverse colon, 1 case on the serous surface of the gastric wall, 1 case in the transverse mesocolon, and 1 case in transverse mesocolon and small mesentery. The clinical manifestations were mostly abdominal distension and abdominal pain. The maximum diameter of the tumor in the surgical resection specimen was 3.5-8.5 cm. The tumor′s cut surface was grayish-white and gray-yellow in color, with medium consistency. Microscopically, the tumor cells were mainly composed of epithelioid tumor cells, and 2 of the tumors showed that tumor cells arranged in a solid sheet or multinodular pattern, and the cytoplasm of the tumor cells was abundant, lightly stained, and the boundaries were unclear, accompanied by the formation of capsules or microcapsules, and lymphocyte and plasma cell sleeves were seen. In one case, the pseudopapillary arrangement was present, and the tumor cells were radially distributed around the fibrovascular axis. In another case, it was arranged in a pseudoacinar pattern, and the nest was surrounded by slender reticular fibers. Immunohistochemistry showed that tumor cells expressed CKpan (4/4) and WT1 (4/4, including 1 focal positive). Vimentin, CK8/18, D2-40 and S-100 were expressed in various intensities, while Calretinin was locally positive or negative. FISH showed that 2 cases had EWSR1 break-apart and 2 cases had FUS break-apart. NGS confirmed the presence of EWSR1::CREM fusion (1 case) and FUS::CREM fusion (2 cases), respectively. Except for 1 recently diagnosed case, 3 cases were followed up: 1 patient died due to tumor recurrence and metastasis (overall survival was 33 months), and 2 patients survived (1 case had recurrence 58 months after surgery, and 1 case had no recurrence or metastasis after surgery).Conclusions:CKpan-positive EWSR1/FUS::CREB fusion malignant tumor is a rare malignancy tumor with undetermined classification that tends to occur in the abdominopelvic cavity and often involves the gastrointestinal tract. Molecular testing such as FISH and NGS is helpful for a definitive diagnosis.
8.Efficacy and safety of dye-free submucosal injection solution for gastric endoscopic submucosal dissection
Wan LU ; Yonggang DING ; Ting ZHANG ; Lijuan MAO ; Jing CHEN ; Yuhong ZHOU ; Jun XIAO ; Wenjie LI ; Yaohui WANG ; Qide ZHANG
Chinese Journal of Digestive Endoscopy 2025;42(10):823-827
To evaluate the efficacy and safety of dye-free submucosal injection solution for gastric endoscopic submucosal dissection (ESD), a retrospective cohort study was performed on data of inpatients with early gastric cancer and precancerous lesions who underwent ESD at the Digestive Endoscopy Center of Jiangsu Province Hospital of Traditional Chinese Medicine from January to December 2020. Cases were divided into dye-free submucosal injection solution group (the observation group) and dye-containing solution group (the control group). A total of 108 cases met the eligibility criteria for analysis (39 VS 69). Baseline characteristics were comparable between the two groups ( P>0.05). Compared with the control group, the observation group showed similar median procedure time (30.5 min VS 35.0 min), median dissection speed (0.3 cm2/min VS 0.4 cm2/min), mean volume of injection solution used (39.2 mL VS 38.8 mL), en bloc resection rate [100.0% (39/39) VS 98.6% (68/69)], and curative resection rate [97.4% (38/39) VS 97.1% (67/69)] (all P>0.05). Postoperative stay was 3.0±0.8 days in the observation group and 3.2±0.8 days in the control group ( t=-0.908, P=0.378). Delayed bleeding occurred in 3 (7.7%) patients VS 2 (2.9%) patients ( P=0.349), and postoperative infection occurred in 3 (7.7%) patients VS 8 (11.6%) patients ( P=0.743), respectively. In gastric ESD, dye-free submucosal injection solution demonstrates efficacy comparable with dye-containing solution and does not appreciably increase the incidence of intraoperative or postoperative complications.
9.Acute effects of air pollution on pulmonary function and exhaled nitric oxide in children in Shanghai
Jianhui GAO ; Yuhong WANG ; Yichen DING ; Lisha SHI ; Dong XU ; Limin LING ; Li PENG ; Lijun ZHANG
Shanghai Journal of Preventive Medicine 2024;36(3):241-248
ObjectiveTo investigate the acute effects of compound air pollution on children’s respiratory function. MethodsUsing panel group study design, 223 students in five classes of grade 4 from two primary schools (a, b) in Xuhui and Hongkou districts of Shanghai were randomly selected to measure pulmonary function and exhaled nitric oxide (FeNO). The first three tests were carried out from May to June in 2020, and the fourth test was carried out from September to December in 2021. At the same time, the daily and hourly mean values of PM2.5, PM10, SO2, NO2, O3 and CO was collected from the nearby air quality monitoring points of the two schools during the same period , as well as meteorological monitoring data (temperature, humidity, wind speed and atmospheric pressure). The linear mixed effect model was used to analyze the effects of air pollution on pulmonary function and respiratory inflammation in the summer. ResultsThe results of single pollutant model showed that PM2.5, PM10, SO2 and NO2 were positively correlated with FeNO, and the effect was reflected in lag0, lag1 and lag3 (P<0.05). PM2.5, PM10 and NO2 were negatively correlated with the changes of lung function FEF25%, FEF50%, FEF75%, FeF25%-75%, PEF, FVC, FEV1 and FEV1/FVC, and the effect was reflected in lag0 to lag3 days (P<0.05). The results of the dual pollutant model showed that the concentration changes of SO2 and NO2 were significantly correlated with the decrease of FEV1 when combined with O3 or PM2.5 (P<0.01), and the concentration changes of PM2.5 was significantly correlated with the increase of FeNO when O3, SO2 and NO2 were combined respectively (P<0.01). The effects of the dual pollutant model were greater than the effect of PM2.5 single pollutant model. ConclusionThe health effects of different air pollutants on children’s respiratory tract function indexes in summer are different. The combined effects of two pollutants on the lung function of children increased to different degrees. Although air pollution is light in summer, it still has an impact on children’s respiratory tract function index and inflammation index, and the combined effect of dual pollutants is more significant than that of single pollutant.
10.PM 2.5-Metabolic Syndrome Causal Association: A Mendelian Randomization Study.
Fan DING ; Ning MA ; Shi ZHAO ; Qingan WANG ; Zhanbing MA ; Yuhong ZHANG ; Yi ZHAO ; Yu ZHAO
Biomedical and Environmental Sciences 2024;37(12):1421-1426

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