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.

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.

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.

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.

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.

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.

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.

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.

Purpose To investigate the diagnosis and the clinicopathological characteristics of gastric adenocarcinoma with enteroblastic differentiation(GAED)in biopsy,and to provide data for the pathological evaluation of endoscopic resection of early gastric cancer.Methods 26 GAED biopsy specimens were collected,and the clinicopathological features were ana-lyzed by re-reading slides,immunohistochemistry and with paired radical surgery specimen.Results Serum AFP was de-tected in 16 patients before operation,and 11 patients(68.75％)were elevated.The initial diagnosis rate and follow-up rate of GAED in biopsy were 42.31％and 92.31％.Among the biopsy specimens,5 cases of GAED were accompanied by conventional gastric adenocarcinoma,and the positive rates of SALL4 and Glypican-3 were high(both 78.57％).The accom-panying cancers in the radical resection specimens include con-ventional gastric adenocarcinoma,hepatoid adenocarcinoma,and low adhesion adenocarcinoma,with the positive rate of SALL4(81.25％),Glypican-3(75％),and AFP(62.5％).GAED was more prone to deep invasion of the gastric wall and lymph node metastasis than conventional gastric adenocarcinoma.A-mong the 6 cases of early GAED,3 cases(50％)were lymph node-positive.Conclusion GAED is easy to be missed in biop-sy,and more attention should be paid to its tissue morphology and immunophenotype.GAED needs to be excluded in the histo-logical type of endoscopic curative resection of early gastric canc-er.

Purpose To investigate the diagnosis and the clinicopathological characteristics of gastric adenocarcinoma with enteroblastic differentiation(GAED)in biopsy,and to provide data for the pathological evaluation of endoscopic resection of early gastric cancer.Methods 26 GAED biopsy specimens were collected,and the clinicopathological features were ana-lyzed by re-reading slides,immunohistochemistry and with paired radical surgery specimen.Results Serum AFP was de-tected in 16 patients before operation,and 11 patients(68.75％)were elevated.The initial diagnosis rate and follow-up rate of GAED in biopsy were 42.31％and 92.31％.Among the biopsy specimens,5 cases of GAED were accompanied by conventional gastric adenocarcinoma,and the positive rates of SALL4 and Glypican-3 were high(both 78.57％).The accom-panying cancers in the radical resection specimens include con-ventional gastric adenocarcinoma,hepatoid adenocarcinoma,and low adhesion adenocarcinoma,with the positive rate of SALL4(81.25％),Glypican-3(75％),and AFP(62.5％).GAED was more prone to deep invasion of the gastric wall and lymph node metastasis than conventional gastric adenocarcinoma.A-mong the 6 cases of early GAED,3 cases(50％)were lymph node-positive.Conclusion GAED is easy to be missed in biop-sy,and more attention should be paid to its tissue morphology and immunophenotype.GAED needs to be excluded in the histo-logical type of endoscopic curative resection of early gastric canc-er.