Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like re...Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in the neuroinflammatory response elicited by brain injury,the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still unclear.We hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with HIBD.Hence,we established a neonatal HIBD rat model using the Rice-Vannucci method,and injected 0.75,1.5,or 3 mg/kg of the TLR4 inhibitor resatorvid(TAK-242)30 minutes after hypoxic ischemia.Our results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema,alleviate neuronal damage and neurobehavioral impairment,and decrease the expression levels of TLR4,phospho-NF-κB p65,Beclin-1,microtubule-associated protein l light chain 3,tumor necrosis factor-α,and interleukin-1βin the hippocampus.Thus,TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling pathway.This study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University,China(approval No.20180114-15)on January 14,2018.展开更多
Yolk sac tumors (YSTs) are rare malignant germ cell tumors that usually affect youngfemales. To date, there have been few studies on YSTs. We evaluated the relationship betweenclinicopathologic characteristics of pati...Yolk sac tumors (YSTs) are rare malignant germ cell tumors that usually affect youngfemales. To date, there have been few studies on YSTs. We evaluated the relationship betweenclinicopathologic characteristics of patients with ovarian YSTs and disease outcome based onSurveillance, Epidemiology, and End Results data. The K aplan-Meier method and log-rank testwere used to evaluate differences in survival rates. Data for 269 patients were analyzed. Theincidence of YSTs among ovarian germ cell tumors (OGCTs) cases was 0.4%;median patient agewas 22.0 years, and most tumors were unilateral. Patients presented with distant metastasis (37.5%),localized disease (49. 1%), and regional spread (8.9%). American Joint Committee on Cancer stagewas available for 13 patients (stage IA, n=2;stage IC, n=1;stage IA, n=1;stage IB, n=3;stageIlC, n=2;and stage IV, n=4). Survival rates at 1, 3, and 5 years were 91.0%, 84.0%, and 83.2%,respectively, for overall survival (OS) and 92.0%, 85.4%, and 84.5%, respectively, for disease-specific survival (DSS). The 5-year OS and DSS of patients with ovary tumors were 91.5% and92.9%, respectively, compared to 74.8% and 77.2%, respectively, for those with extra-ovarianspread (P<0.001 for both OS and DSS). Age >50 years was associated with shorter OS and DSS(both P<0.001), whereas no associatios of OS and DSS were observed with pathologic grade (P=0.49for OS and 0.52 for DSS). In summary, YSTs are typically unilateral, of a high grade, and localizedto the ovary;extra-ovarian spread has a poor outcome, and postmenopausal women have worseprognosis than premenopausal women.展开更多
BACKGROUND Normal size ovarian cancer syndrome(NOCS)is a challenge for clinicians regarding timely diagnosis and management due to atypical clinical and imaging features.It is extremely rare with only a few cases repo...BACKGROUND Normal size ovarian cancer syndrome(NOCS)is a challenge for clinicians regarding timely diagnosis and management due to atypical clinical and imaging features.It is extremely rare with only a few cases reported in the literature.More data are needed to clarify its biological behavior and compare the differences with abnormal size ovarian cancer.AIM To assess the clinical and pathological features of NOCS patients treated in our institution in the last 10 years and to explore risk factors for relapse and survival.METHODS Patients who were pathologically diagnosed with NOCS between 2008 and 2018 were included.Papillary serous ovarian carcinoma(PSOC)patients were initially randomly recruited as the control group.Demographics,tumor characteristics,treatment procedures,and clinical follow-up were retrospectively collected.Risk factors for progression-free survival and overall survival were assessed.RESULTS A total of 110 NOCS patients were included;80(72.7%)had primary adnexal carcinoma,two(1.8%)had mesotheliomas,18(16.4%)had extraovarian peritoneal serous papillary carcinoma,and eight(7.3%)had metastatic tumors.Carbohydrate antigen(CA)125 and ascites quantity were lower in the NOCS cohort than in the PSOC group.The only statistically significant risk factors for worse overall survival(P<0.05)were the levels of CA199 and having fewer than six chemotherapy cycles.The 1-year,3-year,and 5-year survival rates were 75.5%,27.7%,and 13.8%,respectively.CONCLUSION The clinical symptoms of the NOCS group are atypical,and the misdiagnosis rate is high.Ascites cytology and laparoscopic exploration are valuable in the early diagnosis to avoid a misdiagnosis.The level of CA199 is the most important predictor of overall survival,and more than six cycles of chemotherapy contributes to the increased survival rates of NOCS patients.展开更多
基金financially supported by the National Natural Science Foundation of China,No.81771625(to XF)the Jiangsu Provincial Key Medical Discipline of China,No.ZDXKA2016013(to XF)the Pediatric Clinical Center of Suzhou City of China,No.Szzx201504(to XF)
文摘Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in the neuroinflammatory response elicited by brain injury,the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still unclear.We hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with HIBD.Hence,we established a neonatal HIBD rat model using the Rice-Vannucci method,and injected 0.75,1.5,or 3 mg/kg of the TLR4 inhibitor resatorvid(TAK-242)30 minutes after hypoxic ischemia.Our results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema,alleviate neuronal damage and neurobehavioral impairment,and decrease the expression levels of TLR4,phospho-NF-κB p65,Beclin-1,microtubule-associated protein l light chain 3,tumor necrosis factor-α,and interleukin-1βin the hippocampus.Thus,TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling pathway.This study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University,China(approval No.20180114-15)on January 14,2018.
文摘Yolk sac tumors (YSTs) are rare malignant germ cell tumors that usually affect youngfemales. To date, there have been few studies on YSTs. We evaluated the relationship betweenclinicopathologic characteristics of patients with ovarian YSTs and disease outcome based onSurveillance, Epidemiology, and End Results data. The K aplan-Meier method and log-rank testwere used to evaluate differences in survival rates. Data for 269 patients were analyzed. Theincidence of YSTs among ovarian germ cell tumors (OGCTs) cases was 0.4%;median patient agewas 22.0 years, and most tumors were unilateral. Patients presented with distant metastasis (37.5%),localized disease (49. 1%), and regional spread (8.9%). American Joint Committee on Cancer stagewas available for 13 patients (stage IA, n=2;stage IC, n=1;stage IA, n=1;stage IB, n=3;stageIlC, n=2;and stage IV, n=4). Survival rates at 1, 3, and 5 years were 91.0%, 84.0%, and 83.2%,respectively, for overall survival (OS) and 92.0%, 85.4%, and 84.5%, respectively, for disease-specific survival (DSS). The 5-year OS and DSS of patients with ovary tumors were 91.5% and92.9%, respectively, compared to 74.8% and 77.2%, respectively, for those with extra-ovarianspread (P<0.001 for both OS and DSS). Age >50 years was associated with shorter OS and DSS(both P<0.001), whereas no associatios of OS and DSS were observed with pathologic grade (P=0.49for OS and 0.52 for DSS). In summary, YSTs are typically unilateral, of a high grade, and localizedto the ovary;extra-ovarian spread has a poor outcome, and postmenopausal women have worseprognosis than premenopausal women.
基金Supported by National Key Technology R&D Program of China,No.2019YFC1005200,and No.2019YFC1005202National Natural Science Foundation of China,No.81501530,No.81802896,and No.81701530+1 种基金Natural Science Foundation of Hubei Province,No.2017CFB800Hubei Province Health and Family Planning Scientific Research Project,No.WJ2017Z013,and No.WJ2019M127.
文摘BACKGROUND Normal size ovarian cancer syndrome(NOCS)is a challenge for clinicians regarding timely diagnosis and management due to atypical clinical and imaging features.It is extremely rare with only a few cases reported in the literature.More data are needed to clarify its biological behavior and compare the differences with abnormal size ovarian cancer.AIM To assess the clinical and pathological features of NOCS patients treated in our institution in the last 10 years and to explore risk factors for relapse and survival.METHODS Patients who were pathologically diagnosed with NOCS between 2008 and 2018 were included.Papillary serous ovarian carcinoma(PSOC)patients were initially randomly recruited as the control group.Demographics,tumor characteristics,treatment procedures,and clinical follow-up were retrospectively collected.Risk factors for progression-free survival and overall survival were assessed.RESULTS A total of 110 NOCS patients were included;80(72.7%)had primary adnexal carcinoma,two(1.8%)had mesotheliomas,18(16.4%)had extraovarian peritoneal serous papillary carcinoma,and eight(7.3%)had metastatic tumors.Carbohydrate antigen(CA)125 and ascites quantity were lower in the NOCS cohort than in the PSOC group.The only statistically significant risk factors for worse overall survival(P<0.05)were the levels of CA199 and having fewer than six chemotherapy cycles.The 1-year,3-year,and 5-year survival rates were 75.5%,27.7%,and 13.8%,respectively.CONCLUSION The clinical symptoms of the NOCS group are atypical,and the misdiagnosis rate is high.Ascites cytology and laparoscopic exploration are valuable in the early diagnosis to avoid a misdiagnosis.The level of CA199 is the most important predictor of overall survival,and more than six cycles of chemotherapy contributes to the increased survival rates of NOCS patients.
