Pancreatic ductal adenocarcinoma(PDAC)remains one of the most lethal ma-lignancies with limited treatment efficacy.Advances in precision oncology,enabled by next-generation sequencing,have highlighted key molecular ta...Pancreatic ductal adenocarcinoma(PDAC)remains one of the most lethal ma-lignancies with limited treatment efficacy.Advances in precision oncology,enabled by next-generation sequencing,have highlighted key molecular targets.Kirsten rat sarcoma viral oncogene homolog mutations,present in up to 90%of cases,drive aggressive biology,though most variants remain undruggable;allele-specific inhibitors and exosome-based RNA interference are under exploration.Breast cancer susceptibility gene 1/2 mutations occur in 4%-7%of patients,con-ferring sensitivity to platinum agents and poly(ADP-ribose)polymerase inhi-bitors.Other rare but actionable alterations-such as v-raf murine sarcoma viral oncogene homolog B1(V600),neurotrophic tyrosine receptor kinase,fibroblast growth factor receptor 2,and RET fusions-show benefit in tumor-agnostic trials,broadening options for selected subgroups.Immunotherapy is limited,as high tumor mutational burden and mismatch repair deficiency are uncommon in PDAC,though predictive when present.Co-mutations in tumor protein p53,cyclin-dependent kinase inhibitor 2A,and SMAD4 further stratify prognosis and influence therapy response.Cross-cancer analyses underscore the necessity of PDAC-specific strategies despite shared genomic drivers.Collectively,these insights support routine germline and somatic testing,enrollment in biomarker-matched trials,and rational combination strategies,establishing molecular profiling as central to advancing precision treatment in pancreatic cancer.展开更多
Lymph node dissection(lymphadenectomy)remains a critical component of pancreatic cancer surgery,contributing to accurate staging and guiding adjuvant therapy.The debate between standard and extended lymphadenectomy pe...Lymph node dissection(lymphadenectomy)remains a critical component of pancreatic cancer surgery,contributing to accurate staging and guiding adjuvant therapy.The debate between standard and extended lymphadenectomy persists,with evidence showing no significant survival advantage of extended dissection over the standard approach.Extended lymphadenectomy,while increasing the number of lymph nodes retrieved,is associated with longer operative times,greater blood loss,and higher morbidity.More importantly,lymph nodes serve as critical immune hubs,and excessive removal may compromise systemic immune surveillance,which is vital in the context of emerging immunotherapies for pan-creatic cancer.This minireview synthesizes the oncological and immunological perspectives on lymphadenectomy,advocating for a personalized approach to lymph node management in pancreatic cancer surgery,focusing on balancing oncologic outcomes with immune preservation.展开更多
This article discusses Wang et al’s essay.Endoscopic biliary stenting,a less invasive alternative to surgery,is effective for malignant obstructive jaundice.This article summarizes the pathophysiology of biliary obst...This article discusses Wang et al’s essay.Endoscopic biliary stenting,a less invasive alternative to surgery,is effective for malignant obstructive jaundice.This article summarizes the pathophysiology of biliary obstruction,the technical aspects of stenting,and the clinical outcomes.By comparison of endoscopic stenting with percutaneous biliary drainage,improvements and complications are focused on.Additionally,patient selection for stenting and future advancements in stent technology are important.Overall,endoscopic biliary stenting is a valuable palliative option for patients with malignant jaundice,especially those ineligibles for surgery.展开更多
Alcohol-related liver disease(ARLD)remains a major public health concern,often diagnosed at advanced stages with limited treatment options.Early identification of high-risk individuals is crucial for timely interventi...Alcohol-related liver disease(ARLD)remains a major public health concern,often diagnosed at advanced stages with limited treatment options.Early identification of high-risk individuals is crucial for timely intervention and improved patient outcomes.Artificial intelligence(AI)has emerged as a powerful tool for predicting ARLD,leveraging multi-omics data,machine learning algorithms,and non-invasive biomarkers.This review explores the current advancements in AIdriven ARLD prediction,highlighting key methodologies such as multi-omics data integration,gut microbiome-based modeling,and predictive analytics using machine learning techniques.AI models incorporating transcriptomics,proteomics,and clinical data have demonstrated high diagnostic accuracy,with some achieving an area under the curve exceeding 0.90.Furthermore,non-invasive biomarkers,including liver stiffness measurements and circulating proteomic panels,have been successfully integrated into AI frameworks for early detection and risk stratification.Despite these advancements,challenges such as data heterogeneity,model generalizability,and ethical considerations remain.Future directions include the development of advanced biomarker discovery,wearable and point-of-care AI-integrated technologies,and precision medicine approaches tailored to individual risk profiles.AI-driven models hold significant potential in transforming ARLD prediction and management,ultimately contributing to early diagnosis and improved clinical outcomes.展开更多
Colorectal cancer(CRC)is a prevalent malignancy,with surgery playing a key role in its treatment.However,perioperative complications,such as anastomotic leaks,infections,and mortality,can significantly affect surgical...Colorectal cancer(CRC)is a prevalent malignancy,with surgery playing a key role in its treatment.However,perioperative complications,such as anastomotic leaks,infections,and mortality,can significantly affect surgical outcomes,extend hospital stays,and increase healthcare costs.Traditional risk prediction models often lack precision,leading to increased interest in artificial intelligence(AI)for improving risk stratification.This review examines the application of AI,particularly machine learning and deep learning,in predicting perioperative complications in CRC surgery.AI models have been employed to predict a variety of postoperative complications,including readmissions,surgical-site infections,anastomotic leakage,and mortality,by analyzing diverse data sources such as electronic health records,medical imaging,and preoperative markers.Despite the promising results,several challenges remain,including data quality,model generalizability,the complexity of clinical data,and ethical and regulatory concerns.The review emphasizes the need for multicenter,diverse datasets and the integration of AI into clinical workflows to improve model performance and adoption.Future efforts should focus on enhancing the transparency and interpretability of AI models to ensure their successful implementation in clinical practice,ultimately improving patient outcomes and surgical decision-making in CRC surgery.展开更多
This editorial discusses Pellegrino and Gravina's essay.Crohn’s disease(CD)is a complex and multifactorial disease that is influenced by a combination of genetic and environmental factors.While genetic factors pl...This editorial discusses Pellegrino and Gravina's essay.Crohn’s disease(CD)is a complex and multifactorial disease that is influenced by a combination of genetic and environmental factors.While genetic factors play a key role in the deve-lopment of the disease,environmental factors also play a significant role in influencing the risk of developing CD.By looking at present understanding of CD pathogenesis,we emphasize the important factors involved in the development of this illness,such as nucleotide-binding oligomerization domain-2,smoking,and vitamin D.Understanding the interplay between genetic and environmental factors is crucial for developing effective strategies for preventing and treating this chronic inflammatory bowel disease.展开更多
This article discusses the article written by Tan et al.Transarterial chemoembol-ization(TACE)is one of the main treatment methods for advanced hepatocellular carcinoma(HCC).There are other vascular interventional the...This article discusses the article written by Tan et al.Transarterial chemoembol-ization(TACE)is one of the main treatment methods for advanced hepatocellular carcinoma(HCC).There are other vascular interventional therapies,including drug-eluting bead TACE,transarterial radioembolization,and hepatic arterial infusion chemotherapy.TACE combined with anti-angiogenesis therapy may improve tumor control and prolong progression free survival.The combination therapy of TACE and immunotherapy may improve the clinical efficacy of HCC.In future research,more basic and clinical studies are needed to explore the immunogenic intervention therapy.展开更多
BACKGROUND Sclerosing angiomatoid nodular transformation(SANT)is a rare disease of the spleen.It has unique pathological features and mimics splenic tumor on radiological imaging.CASE SUMMARY A 47-year-old woman was i...BACKGROUND Sclerosing angiomatoid nodular transformation(SANT)is a rare disease of the spleen.It has unique pathological features and mimics splenic tumor on radiological imaging.CASE SUMMARY A 47-year-old woman was incidentally found to have a splenic mass on abdominal ultrasound.She had a 10-cm postoperative scar in the lower abdomen due to previous cesarean sections.The patient had a past history of anemia of unknown etiology for 20 years.The patient underwent laparoscopic splenectomy.The postoperative course was uneventful,with a hospital stay of 7 d.The histopathological examination of the spleen revealed SANT.At the 6-mo followup,the patient remained disease-free.CONCLUSION SANT is a rare benign disease mimicking a malignant tumor.A definitive diagnosis can be made only on histopathology.展开更多
BACKGROUND Myxomas are benign tumors of mesenchymal origin that rarely occur in the larynx.CASE SUMMARY We report a case of a laryngeal myxoma that presented as a right vocal cord mass in a 54-year-old man.CONCLUSION ...BACKGROUND Myxomas are benign tumors of mesenchymal origin that rarely occur in the larynx.CASE SUMMARY We report a case of a laryngeal myxoma that presented as a right vocal cord mass in a 54-year-old man.CONCLUSION Laryngeal myxoma is a rare benign tumor in the larynx.It is difficult to distinguish glottis myxoma from vocal cord polyps on laryngoscopy.We recommend that otolaryngologists acquire a better understanding of this disease.If a laryngeal myxoma is suspected,dynamic laryngoscopy,acoustic voice analysis,and pathological biopsy should be performed.展开更多
BACKGROUND In orthotopic liver transplantation(OLT)recipients,median arcuate ligament syndrome(MALS)is considered a risk factor for hepatic arterial thrombosis(HAT),which is dreadful for OLT recipients.Different alter...BACKGROUND In orthotopic liver transplantation(OLT)recipients,median arcuate ligament syndrome(MALS)is considered a risk factor for hepatic arterial thrombosis(HAT),which is dreadful for OLT recipients.Different alternative surgical procedures have been proposed to overcome the impact of MALS on transplantation,but clinical evidence is still scarce.AIM To evaluate the feasible surgical management of MALS to reduce complications in OLT patients.METHODS Data for 288 consecutive patients who underwent OLT at The First Hospital of Jilin University between January 2017 and July 2020 were retrospectively reviewed.The surgical management of median arcuate ligament(MAL)and modifications to the arterial anastomosis were recorded.The perioperative and long-term prognosis of MALS recipients were noted.Detailed preoperative and postoperative data of patients were analyzed in a descriptive manner.RESULTS Eight patients with MALS were included in this study.The first patient with MALS received no intervention during the primary surgery and developed postoperative HAT.Salvage liver transplantation with MAL division was successfully performed.Gastroduodenal artery(GDA)preservation with splenic artery ligation was performed on three patients,only GDA preservation was performed on two patients,and no intervention was performed on two patients.No patient developed HAT after surgery and postoperative recovery was satisfactory.CONCLUSION The preservation of collateral circulation between the superior mesenteric artery and celiac trunk via the GDA with or without splenic artery ligation is a safe and feasible alternative to MAL division.展开更多
Biliary leakage is a potentially life-threatening complication following liver transplantation and is associated with significant postoperative morbidity,prolonged hospitalization,and potential graft failure.Its incid...Biliary leakage is a potentially life-threatening complication following liver transplantation and is associated with significant postoperative morbidity,prolonged hospitalization,and potential graft failure.Its incidence underscores the need for timely diagnosis and effective intervention.Diagnostic modalities such as magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography offer both anatomical and functional insights.Endoscopic management with endoscopic retrograde cholangiopancreatography remains the mainstay of treatment,while percutaneous transhepatic cholangiography offers an alternative in patients with altered anatomy or failed endoscopic access.Surgical revision is considered a last resort after other methods have failed.Preventive strategies,including machine perfusion and meticulous surgical techniques,are essential in reducing incidence and improving outcomes.This editorial provides a comprehensive overview of clinical management and therapeutic strategies for biliary leakage after liver transplantation.展开更多
Microsatellite instability(MSI)is a critical molecular feature in colorectal cancer(CRC)that not only determines response to immunotherapy but also influences systemic nutritional and inflammatory status.MSI-high(MSI-...Microsatellite instability(MSI)is a critical molecular feature in colorectal cancer(CRC)that not only determines response to immunotherapy but also influences systemic nutritional and inflammatory status.MSI-high(MSI-H)CRC is characterized by heightened systemic inflammation,altered cytokine profiles,and unique gut microbiota compositions.Concurrently,MSI-H patients often exhibit poorer nutritional status,as reflected by lower body mass index,decreased serum albumin,and metabolic dysregulation.These immunonutritional alterations influence patient outcomes by affecting prognosis,response to therapy,and overall survival.This editorial summarizes current evidence linking MSI status with inflammatory and nutritional markers,highlighting the clinical implications of integrating nutritional assessment and inflammatory modulation into the maagement of CRC patients.展开更多
Background： MicroRNAs （miRNAs） are key regulators during tumor initiation and progression. MicroRNA-375 （MiR-375） has been proven to play a tumor-suppressive role in various types of human malignancies; however, ...Background： MicroRNAs （miRNAs） are key regulators during tumor initiation and progression. MicroRNA-375 （MiR-375） has been proven to play a tumor-suppressive role in various types of human malignancies; however, its biological role in clear cell renal cell carcinoma （ccRCC） remains unclear. The purpose of this study was to explore the biologic role as well as the underlying mechanism of miR-375 in ccRCC progression. Methods： Quantitative polymerase chain reaction （qPCR） was applied to test the expression of miR-375 in tissues and cell lines by t-test. Functional experiments were used to investigate the biological role of miR-375 utilizing a gain-of-function strategy. The target of miR-375 was investigated by bioinformatic analysis and further verified by luciferase reporter assay, qPCR, Western blotting, and functional experiments in vitro. Results： Our study demonstrated that miR-375 was significantly downregulated in ccRCC tissues （cancer vs. normal, 0.804 ±0.079 vs. 1.784 ± 0.200, t = 5.531 P 〈 0.0001 ） and cell lines, and loss ofmiR-375 expression significantly associated with advanced Fuhrman nuclear grades （Grade Ⅲ and Ⅳ vs. Grade Ⅰ and Ⅱ, 1.000 ± 0.099 vs. 1.731 ± 0.189, t = 3.262 P = 0.003）. Functional studies demonstrated that miR-375 suppressed ccRCC cell proliferation, migration, and invasion （all P 〈 0.05 in both 786-0 and A498 cell lines）. Multiple miRNA target prediction algorithms indicated the well-studied oncogene YWHAZ as a direct target ofmiR-375, which was further confirmed by the luciferase reporter assay, qPCR, and Western blotting. Moreover, restoration of YWHAZ could rescue the antiproliferation effect ofmi R-375. Conclusions： The data provide the solid evidence that miR-375 plays a tumor-suppressive role in ccRCC progression, partially through regulating YWHAZ. This study expands the antitumor profile ofmiR-375, and supports its role as a potential therapeutic target in ccRCC treatment.展开更多
文摘Pancreatic ductal adenocarcinoma(PDAC)remains one of the most lethal ma-lignancies with limited treatment efficacy.Advances in precision oncology,enabled by next-generation sequencing,have highlighted key molecular targets.Kirsten rat sarcoma viral oncogene homolog mutations,present in up to 90%of cases,drive aggressive biology,though most variants remain undruggable;allele-specific inhibitors and exosome-based RNA interference are under exploration.Breast cancer susceptibility gene 1/2 mutations occur in 4%-7%of patients,con-ferring sensitivity to platinum agents and poly(ADP-ribose)polymerase inhi-bitors.Other rare but actionable alterations-such as v-raf murine sarcoma viral oncogene homolog B1(V600),neurotrophic tyrosine receptor kinase,fibroblast growth factor receptor 2,and RET fusions-show benefit in tumor-agnostic trials,broadening options for selected subgroups.Immunotherapy is limited,as high tumor mutational burden and mismatch repair deficiency are uncommon in PDAC,though predictive when present.Co-mutations in tumor protein p53,cyclin-dependent kinase inhibitor 2A,and SMAD4 further stratify prognosis and influence therapy response.Cross-cancer analyses underscore the necessity of PDAC-specific strategies despite shared genomic drivers.Collectively,these insights support routine germline and somatic testing,enrollment in biomarker-matched trials,and rational combination strategies,establishing molecular profiling as central to advancing precision treatment in pancreatic cancer.
文摘Lymph node dissection(lymphadenectomy)remains a critical component of pancreatic cancer surgery,contributing to accurate staging and guiding adjuvant therapy.The debate between standard and extended lymphadenectomy persists,with evidence showing no significant survival advantage of extended dissection over the standard approach.Extended lymphadenectomy,while increasing the number of lymph nodes retrieved,is associated with longer operative times,greater blood loss,and higher morbidity.More importantly,lymph nodes serve as critical immune hubs,and excessive removal may compromise systemic immune surveillance,which is vital in the context of emerging immunotherapies for pan-creatic cancer.This minireview synthesizes the oncological and immunological perspectives on lymphadenectomy,advocating for a personalized approach to lymph node management in pancreatic cancer surgery,focusing on balancing oncologic outcomes with immune preservation.
文摘This article discusses Wang et al’s essay.Endoscopic biliary stenting,a less invasive alternative to surgery,is effective for malignant obstructive jaundice.This article summarizes the pathophysiology of biliary obstruction,the technical aspects of stenting,and the clinical outcomes.By comparison of endoscopic stenting with percutaneous biliary drainage,improvements and complications are focused on.Additionally,patient selection for stenting and future advancements in stent technology are important.Overall,endoscopic biliary stenting is a valuable palliative option for patients with malignant jaundice,especially those ineligibles for surgery.
文摘Alcohol-related liver disease(ARLD)remains a major public health concern,often diagnosed at advanced stages with limited treatment options.Early identification of high-risk individuals is crucial for timely intervention and improved patient outcomes.Artificial intelligence(AI)has emerged as a powerful tool for predicting ARLD,leveraging multi-omics data,machine learning algorithms,and non-invasive biomarkers.This review explores the current advancements in AIdriven ARLD prediction,highlighting key methodologies such as multi-omics data integration,gut microbiome-based modeling,and predictive analytics using machine learning techniques.AI models incorporating transcriptomics,proteomics,and clinical data have demonstrated high diagnostic accuracy,with some achieving an area under the curve exceeding 0.90.Furthermore,non-invasive biomarkers,including liver stiffness measurements and circulating proteomic panels,have been successfully integrated into AI frameworks for early detection and risk stratification.Despite these advancements,challenges such as data heterogeneity,model generalizability,and ethical considerations remain.Future directions include the development of advanced biomarker discovery,wearable and point-of-care AI-integrated technologies,and precision medicine approaches tailored to individual risk profiles.AI-driven models hold significant potential in transforming ARLD prediction and management,ultimately contributing to early diagnosis and improved clinical outcomes.
文摘Colorectal cancer(CRC)is a prevalent malignancy,with surgery playing a key role in its treatment.However,perioperative complications,such as anastomotic leaks,infections,and mortality,can significantly affect surgical outcomes,extend hospital stays,and increase healthcare costs.Traditional risk prediction models often lack precision,leading to increased interest in artificial intelligence(AI)for improving risk stratification.This review examines the application of AI,particularly machine learning and deep learning,in predicting perioperative complications in CRC surgery.AI models have been employed to predict a variety of postoperative complications,including readmissions,surgical-site infections,anastomotic leakage,and mortality,by analyzing diverse data sources such as electronic health records,medical imaging,and preoperative markers.Despite the promising results,several challenges remain,including data quality,model generalizability,the complexity of clinical data,and ethical and regulatory concerns.The review emphasizes the need for multicenter,diverse datasets and the integration of AI into clinical workflows to improve model performance and adoption.Future efforts should focus on enhancing the transparency and interpretability of AI models to ensure their successful implementation in clinical practice,ultimately improving patient outcomes and surgical decision-making in CRC surgery.
文摘This editorial discusses Pellegrino and Gravina's essay.Crohn’s disease(CD)is a complex and multifactorial disease that is influenced by a combination of genetic and environmental factors.While genetic factors play a key role in the deve-lopment of the disease,environmental factors also play a significant role in influencing the risk of developing CD.By looking at present understanding of CD pathogenesis,we emphasize the important factors involved in the development of this illness,such as nucleotide-binding oligomerization domain-2,smoking,and vitamin D.Understanding the interplay between genetic and environmental factors is crucial for developing effective strategies for preventing and treating this chronic inflammatory bowel disease.
文摘This article discusses the article written by Tan et al.Transarterial chemoembol-ization(TACE)is one of the main treatment methods for advanced hepatocellular carcinoma(HCC).There are other vascular interventional therapies,including drug-eluting bead TACE,transarterial radioembolization,and hepatic arterial infusion chemotherapy.TACE combined with anti-angiogenesis therapy may improve tumor control and prolong progression free survival.The combination therapy of TACE and immunotherapy may improve the clinical efficacy of HCC.In future research,more basic and clinical studies are needed to explore the immunogenic intervention therapy.
文摘BACKGROUND Sclerosing angiomatoid nodular transformation(SANT)is a rare disease of the spleen.It has unique pathological features and mimics splenic tumor on radiological imaging.CASE SUMMARY A 47-year-old woman was incidentally found to have a splenic mass on abdominal ultrasound.She had a 10-cm postoperative scar in the lower abdomen due to previous cesarean sections.The patient had a past history of anemia of unknown etiology for 20 years.The patient underwent laparoscopic splenectomy.The postoperative course was uneventful,with a hospital stay of 7 d.The histopathological examination of the spleen revealed SANT.At the 6-mo followup,the patient remained disease-free.CONCLUSION SANT is a rare benign disease mimicking a malignant tumor.A definitive diagnosis can be made only on histopathology.
文摘BACKGROUND Myxomas are benign tumors of mesenchymal origin that rarely occur in the larynx.CASE SUMMARY We report a case of a laryngeal myxoma that presented as a right vocal cord mass in a 54-year-old man.CONCLUSION Laryngeal myxoma is a rare benign tumor in the larynx.It is difficult to distinguish glottis myxoma from vocal cord polyps on laryngoscopy.We recommend that otolaryngologists acquire a better understanding of this disease.If a laryngeal myxoma is suspected,dynamic laryngoscopy,acoustic voice analysis,and pathological biopsy should be performed.
基金Supported by the Science and Technology Department of Jilin Province,No.20190101002JH.
文摘BACKGROUND In orthotopic liver transplantation(OLT)recipients,median arcuate ligament syndrome(MALS)is considered a risk factor for hepatic arterial thrombosis(HAT),which is dreadful for OLT recipients.Different alternative surgical procedures have been proposed to overcome the impact of MALS on transplantation,but clinical evidence is still scarce.AIM To evaluate the feasible surgical management of MALS to reduce complications in OLT patients.METHODS Data for 288 consecutive patients who underwent OLT at The First Hospital of Jilin University between January 2017 and July 2020 were retrospectively reviewed.The surgical management of median arcuate ligament(MAL)and modifications to the arterial anastomosis were recorded.The perioperative and long-term prognosis of MALS recipients were noted.Detailed preoperative and postoperative data of patients were analyzed in a descriptive manner.RESULTS Eight patients with MALS were included in this study.The first patient with MALS received no intervention during the primary surgery and developed postoperative HAT.Salvage liver transplantation with MAL division was successfully performed.Gastroduodenal artery(GDA)preservation with splenic artery ligation was performed on three patients,only GDA preservation was performed on two patients,and no intervention was performed on two patients.No patient developed HAT after surgery and postoperative recovery was satisfactory.CONCLUSION The preservation of collateral circulation between the superior mesenteric artery and celiac trunk via the GDA with or without splenic artery ligation is a safe and feasible alternative to MAL division.
文摘Biliary leakage is a potentially life-threatening complication following liver transplantation and is associated with significant postoperative morbidity,prolonged hospitalization,and potential graft failure.Its incidence underscores the need for timely diagnosis and effective intervention.Diagnostic modalities such as magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography offer both anatomical and functional insights.Endoscopic management with endoscopic retrograde cholangiopancreatography remains the mainstay of treatment,while percutaneous transhepatic cholangiography offers an alternative in patients with altered anatomy or failed endoscopic access.Surgical revision is considered a last resort after other methods have failed.Preventive strategies,including machine perfusion and meticulous surgical techniques,are essential in reducing incidence and improving outcomes.This editorial provides a comprehensive overview of clinical management and therapeutic strategies for biliary leakage after liver transplantation.
文摘Microsatellite instability(MSI)is a critical molecular feature in colorectal cancer(CRC)that not only determines response to immunotherapy but also influences systemic nutritional and inflammatory status.MSI-high(MSI-H)CRC is characterized by heightened systemic inflammation,altered cytokine profiles,and unique gut microbiota compositions.Concurrently,MSI-H patients often exhibit poorer nutritional status,as reflected by lower body mass index,decreased serum albumin,and metabolic dysregulation.These immunonutritional alterations influence patient outcomes by affecting prognosis,response to therapy,and overall survival.This editorial summarizes current evidence linking MSI status with inflammatory and nutritional markers,highlighting the clinical implications of integrating nutritional assessment and inflammatory modulation into the maagement of CRC patients.
基金This work was supported by the grants from the National Natural Science Foundation of China （No. 81702521） and Provincial Natural Science Foundation of Shandong （No. ZR2017PH019 and No. ZR2018BH018）.
文摘Background： MicroRNAs （miRNAs） are key regulators during tumor initiation and progression. MicroRNA-375 （MiR-375） has been proven to play a tumor-suppressive role in various types of human malignancies; however, its biological role in clear cell renal cell carcinoma （ccRCC） remains unclear. The purpose of this study was to explore the biologic role as well as the underlying mechanism of miR-375 in ccRCC progression. Methods： Quantitative polymerase chain reaction （qPCR） was applied to test the expression of miR-375 in tissues and cell lines by t-test. Functional experiments were used to investigate the biological role of miR-375 utilizing a gain-of-function strategy. The target of miR-375 was investigated by bioinformatic analysis and further verified by luciferase reporter assay, qPCR, Western blotting, and functional experiments in vitro. Results： Our study demonstrated that miR-375 was significantly downregulated in ccRCC tissues （cancer vs. normal, 0.804 ±0.079 vs. 1.784 ± 0.200, t = 5.531 P 〈 0.0001 ） and cell lines, and loss ofmiR-375 expression significantly associated with advanced Fuhrman nuclear grades （Grade Ⅲ and Ⅳ vs. Grade Ⅰ and Ⅱ, 1.000 ± 0.099 vs. 1.731 ± 0.189, t = 3.262 P = 0.003）. Functional studies demonstrated that miR-375 suppressed ccRCC cell proliferation, migration, and invasion （all P 〈 0.05 in both 786-0 and A498 cell lines）. Multiple miRNA target prediction algorithms indicated the well-studied oncogene YWHAZ as a direct target ofmiR-375, which was further confirmed by the luciferase reporter assay, qPCR, and Western blotting. Moreover, restoration of YWHAZ could rescue the antiproliferation effect ofmi R-375. Conclusions： The data provide the solid evidence that miR-375 plays a tumor-suppressive role in ccRCC progression, partially through regulating YWHAZ. This study expands the antitumor profile ofmiR-375, and supports its role as a potential therapeutic target in ccRCC treatment.
