1.Expert consensus on integrated diagnosis and treatment techniques for oropharyngeal squamous cell carcinoma
Wei SHANG ; Haoyue XU ; Zongxuan HE ; Xiaoying LI ; Haijun LU ; Xiaohong ZHAN ; Dapeng HAO ; Yan SUN ; Wei GUO ; Zhangui TANG ; Guoxin REN ; Zhijun SUN ; Jian MENG ; Jie ZHANG ; Jichen LI ; Yue HE ; Chunjie LI ; Jianhua WEI ; Lizheng QIN ; Yaowu YANG ; Qing XI ; Wei WU ; Kai YANG ; Bing HAN ; Lingxue BU ; Shuangyi WANG ; Kai SONG ; Jiaqi ZHU ; Hongyu HAN ; Yu KONG ; Jieying LI ; Man HU ; Mingjin XU ; Moyi SUN
Journal of Practical Stomatology 2025;41(6):725-736
In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.
2.Efficacy and safety of postoperative adjuvant mitotane therapy in adrenocortical carcinoma at high risk of recurrence
Yi LIU ; Zhan WANG ; Jiayang CHEN ; Jianhua DENG ; Weifeng XU ; Songchen HAN ; Yanan LI ; Xu WANG ; Yang ZHAO ; Yushi ZHANG
Chinese Journal of Urology 2025;46(1):5-9
Objective:To explore the efficacy and safety of mitotane in adrenal cortical carcinoma (ACC) at high risk of recurrence.Methods:A prospective observational study was designed from September 2022 to November 2023. ACC patients undergoing surgery with high recurrence risk (positive margin or Ki-67 index >10% or capsule rupture or large size or high-grade ACC) in Peking Union Medical College Hospital were enrolled in this study. All patients started mitotane treatment within 3 months after surgery, with a dose of 1.5 g/d, increased by 0.5 g per week. Once the dose reached 3 g/day, adjustments were made based on blood concentration levels. All patients received mitotane therapy for at least 1 year, and CT was performed every 12 weeks to evaluate the efficacy. The primary endpoint was 1-year progression-free survival (PFS) and safety. The efficacy was analyzed by Kaplan-Meier method for survival, and the occurrence of treatment-related adverse events was summarized.Results:A total of 12 ACC patients at high risk of recurrence were screened, comprising 6 males and 6 females. Tumors were located on the left side in 8 patients, on the right in 3, and bilaterally in 1. Five patients were classified as ENSAT stageⅡ, while 7 were classified as ENSAT stage Ⅲ. The maximum diameter of tumor was (9.07 ± 2.86) cm; the median age at diagnosis was 48 (35, 51) years, and the median Ki-67 index was (28.9 ± 16.1)%. The median time from surgery to initiation of mitotane therapy was 31 (23.0, 43.2) days, and 9 patients had blood drug concentrations of 14-20 mg/L. The median follow-up time was 16.7 (12.4, 25.2) months. At 1 year after mitotane therapy, 10 (83.8%) patients were still in disease-free survival state, with a median mitotane PFS of 27.6 months (95% CI 16.4-not reached). All ACC patients experienced 1-2 grade adverse events after taking mitotane. One patient (8.3%) experienced grade 3 adverse event, including the increasing of alanine aminotransferase and aspartate aminotransferase, as well as anorexia. No grade 4-5 adverse events occurred. The most common adverse events were gastrointestinal symptoms (10 cases), including nausea, vomiting, anorexia, and diarrhea, followed by liver function damage(9 cases) and neurotoxicity(4 cases). Conclusions:Mitotane has shown the prospect of improving the prognosis of ACC patients at high risk of recurrence after surgery. Because of its serious toxic and side effects, it is necessary to monitor its blood concentration to adjust the dosage, and take measures for adverse reactions to ensure the safety of patients.
3.Differences in clinical and pathological features between conventional adrenocortical carcinoma and oncocytic adrenocortical carcinoma
Jiang LIU ; Zhan WANG ; Songchen HAN ; Yi LIU ; Yang ZHAO ; Jianhua DENG ; Yushi ZHANG
Chinese Journal of Urology 2025;46(7):523-528
Objective:To explore the differences in clinicopathological features and prognosis between conventional adrenocortical carcinoma(ACC)and oncocytic ACC.Methods:The clinical and pathological data of patients with conventional ACC and oncocytic ACC who were admitted to Peking Union Medical College Hospital from March 2012 to Fabruary 2025 were retrospectively analyzed. Differences in clinical and pathological characteristics between the two groups were compared. Survival curves were plotted using the Kaplan-Meier method,and differences in survival rates were compared using the log-rank test.Results:The conventional ACC group comprised 137 cases,with a mean age of(47.5 ± 12.6)years and 37.2%(51/137)being male. The oncocytic ACC group included 22 cases,with a mean age of(49.1 ± 15.3)years and 59.1%(13/22)being male. No statistically significant differences were observed in age or gender distribution between the two groups( P > 0.05). The conventional ACC group exhibited a significantly higher prevalence of classic Cushing’s syndrome symptoms compared to the oncocytic ACC group[35.2%(45/128)vs. 5.3%(1/19); χ2 = 6.876, P < 0.01]. Additionally,the proportion of hypertension was higher in the conventional ACC group[49.2%(65/132)vs. 22.2%(4/18); χ2 = 5.319, P < 0.05],whereas the prevalence of adrenal sex characteristics was lower[22.0%(28/127)vs. 63.2%(12/19); χ2 = 14.043, P < 0.01]. The Ki-67 proliferation index was significantly higher in conventional ACC patients[20%(10%,40%)vs. 12%(9%,20%); Z = -2.113, P < 0.05]. Furthermore,the conventional ACC group demonstrated a lower 5-year overall survival rate than the oncocytic ACC group(44.5% vs. 67.3%, P < 0.05). Conclusions:Conventional ACC patients have a higher proportion of Cushing’s symptoms and hypertension,and oncocytic ACC patients have a higher proportion of adrenal sexual characteristics abnormalities. The prognosis of oncocytic ACC is better than that of conventional ACC.
4.Lycopene activates the LXR/PI3K/Akt pathway to mediate mitochondrial activity af-fecting myocardial microvascular remodeling
Ting LUO ; Zhan LI ; Shan LI ; Jianhua ZHOU ; Yan HUANG ; Fengbo FU
Chinese Journal of Arteriosclerosis 2025;33(2):108-116
Aim To investigate the effects of lycopene on myocardial microvascular remodeling and elucidate its underlying mechanisms via the LXR/PI3K/Akt pathway.Methods 50 SD rats were selected to establish a coronary microcirculation disorder model and divided into sham,model and low/mid/high concentration lycopene groups.Left ven-tricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in rats were detected using echocardiography,creatine kinase(CK),lactate dehydrogenase(LDH),vascular endothelial growth factor(VEGF),platelet-derived growth factor(PDGF)were detected using ELISA,matrix metalloproteinase-9(MMP-9),matrix metalloproteinase-2(MMP-2)and PI3K/Akt pathway related protein expression were detected using Western blot,and liver X receptor α(LXRα)and liver X receptor β(LXRβ)expression were detected using immunohistochemical staining.In vitro,a hypoxia model of myo-cardial microvascular endothelial cells(MCMEC)was established,with groups including control,hypoxia,hypoxia+low/mid/high concentration lycopene,LXR/PI3K/Akt pathway inhibitor group and mitochondrial fission inhibitor group.Cell viability was detected using CCK-8,LXRα and LXRβ were detected using immunofluorescence,superoxide dismutase(SOD),reactive oxygen species(ROS),VEGF and PDGF levels were detected using ELISA,mitochondrial function-re-lated proteins(Drp1,Fis1,LC3-Ⅱ/LC3-Ⅰ,PINK1,Parkin and Opa1)and MMP-9,MMP-2 and PI3K/Akt pathway related proteins were detected using Western blot,and myocardial tissue injury was evaluated using HE staining.Results Compared with the sham group,the model group exhibited severe myocardial injury,with increased levels of LVEDD,LVESD,CK and LDH,decreased LVEF and LVFS,downregulated expression of VEGF,PDGF,MMP-9 and MMP-2,de-creased expression of p-PI3K/PI3K and p-Akt/Akt,and downregulated expression of LXRα and LXRβ.In cells,com-pared with the control group,the hypoxia group showed decreased cell viability,downregulated expression of VEGF,PDGF,MMP-9,and MMP-2,and decreased expression of p-PI3K/PI3K and p-Akt/Akt.Lycopene treatment could ef-fectively reverse the above changes and increase the expression of LXRα and LXRβ.Moreover,lycopene could also re-verse and modulate the characteristic alterations of Drp1,Fis1,LC3-Ⅱ/LC3-Ⅰ,PINK1,Parkin and Opa1 induced by LXR/PI3K/Akt pathway inhibitors or mitochondrial fission inhibitors.Conclusion Lycopene enhances mitochondrial activi-ty,reduces oxidative stress and improves myocardial microvascular remodeling by activating the LXR/PI3K/Akt pathway.
5.Lycopene activates the LXR/PI3K/Akt pathway to mediate mitochondrial activity af-fecting myocardial microvascular remodeling
Ting LUO ; Zhan LI ; Shan LI ; Jianhua ZHOU ; Yan HUANG ; Fengbo FU
Chinese Journal of Arteriosclerosis 2025;33(2):108-116
Aim To investigate the effects of lycopene on myocardial microvascular remodeling and elucidate its underlying mechanisms via the LXR/PI3K/Akt pathway.Methods 50 SD rats were selected to establish a coronary microcirculation disorder model and divided into sham,model and low/mid/high concentration lycopene groups.Left ven-tricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in rats were detected using echocardiography,creatine kinase(CK),lactate dehydrogenase(LDH),vascular endothelial growth factor(VEGF),platelet-derived growth factor(PDGF)were detected using ELISA,matrix metalloproteinase-9(MMP-9),matrix metalloproteinase-2(MMP-2)and PI3K/Akt pathway related protein expression were detected using Western blot,and liver X receptor α(LXRα)and liver X receptor β(LXRβ)expression were detected using immunohistochemical staining.In vitro,a hypoxia model of myo-cardial microvascular endothelial cells(MCMEC)was established,with groups including control,hypoxia,hypoxia+low/mid/high concentration lycopene,LXR/PI3K/Akt pathway inhibitor group and mitochondrial fission inhibitor group.Cell viability was detected using CCK-8,LXRα and LXRβ were detected using immunofluorescence,superoxide dismutase(SOD),reactive oxygen species(ROS),VEGF and PDGF levels were detected using ELISA,mitochondrial function-re-lated proteins(Drp1,Fis1,LC3-Ⅱ/LC3-Ⅰ,PINK1,Parkin and Opa1)and MMP-9,MMP-2 and PI3K/Akt pathway related proteins were detected using Western blot,and myocardial tissue injury was evaluated using HE staining.Results Compared with the sham group,the model group exhibited severe myocardial injury,with increased levels of LVEDD,LVESD,CK and LDH,decreased LVEF and LVFS,downregulated expression of VEGF,PDGF,MMP-9 and MMP-2,de-creased expression of p-PI3K/PI3K and p-Akt/Akt,and downregulated expression of LXRα and LXRβ.In cells,com-pared with the control group,the hypoxia group showed decreased cell viability,downregulated expression of VEGF,PDGF,MMP-9,and MMP-2,and decreased expression of p-PI3K/PI3K and p-Akt/Akt.Lycopene treatment could ef-fectively reverse the above changes and increase the expression of LXRα and LXRβ.Moreover,lycopene could also re-verse and modulate the characteristic alterations of Drp1,Fis1,LC3-Ⅱ/LC3-Ⅰ,PINK1,Parkin and Opa1 induced by LXR/PI3K/Akt pathway inhibitors or mitochondrial fission inhibitors.Conclusion Lycopene enhances mitochondrial activi-ty,reduces oxidative stress and improves myocardial microvascular remodeling by activating the LXR/PI3K/Akt pathway.
6.Expert consensus on integrated diagnosis and treatment techniques for oropharyngeal squamous cell carcinoma
Wei SHANG ; Haoyue XU ; Zongxuan HE ; Xiaoying LI ; Haijun LU ; Xiaohong ZHAN ; Dapeng HAO ; Yan SUN ; Wei GUO ; Zhangui TANG ; Guoxin REN ; Zhijun SUN ; Jian MENG ; Jie ZHANG ; Jichen LI ; Yue HE ; Chunjie LI ; Jianhua WEI ; Lizheng QIN ; Yaowu YANG ; Qing XI ; Wei WU ; Kai YANG ; Bing HAN ; Lingxue BU ; Shuangyi WANG ; Kai SONG ; Jiaqi ZHU ; Hongyu HAN ; Yu KONG ; Jieying LI ; Man HU ; Mingjin XU ; Moyi SUN
Journal of Practical Stomatology 2025;41(6):725-736
In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.
7.Efficacy and safety of postoperative adjuvant mitotane therapy in adrenocortical carcinoma at high risk of recurrence
Yi LIU ; Zhan WANG ; Jiayang CHEN ; Jianhua DENG ; Weifeng XU ; Songchen HAN ; Yanan LI ; Xu WANG ; Yang ZHAO ; Yushi ZHANG
Chinese Journal of Urology 2025;46(1):5-9
Objective:To explore the efficacy and safety of mitotane in adrenal cortical carcinoma (ACC) at high risk of recurrence.Methods:A prospective observational study was designed from September 2022 to November 2023. ACC patients undergoing surgery with high recurrence risk (positive margin or Ki-67 index >10% or capsule rupture or large size or high-grade ACC) in Peking Union Medical College Hospital were enrolled in this study. All patients started mitotane treatment within 3 months after surgery, with a dose of 1.5 g/d, increased by 0.5 g per week. Once the dose reached 3 g/day, adjustments were made based on blood concentration levels. All patients received mitotane therapy for at least 1 year, and CT was performed every 12 weeks to evaluate the efficacy. The primary endpoint was 1-year progression-free survival (PFS) and safety. The efficacy was analyzed by Kaplan-Meier method for survival, and the occurrence of treatment-related adverse events was summarized.Results:A total of 12 ACC patients at high risk of recurrence were screened, comprising 6 males and 6 females. Tumors were located on the left side in 8 patients, on the right in 3, and bilaterally in 1. Five patients were classified as ENSAT stageⅡ, while 7 were classified as ENSAT stage Ⅲ. The maximum diameter of tumor was (9.07 ± 2.86) cm; the median age at diagnosis was 48 (35, 51) years, and the median Ki-67 index was (28.9 ± 16.1)%. The median time from surgery to initiation of mitotane therapy was 31 (23.0, 43.2) days, and 9 patients had blood drug concentrations of 14-20 mg/L. The median follow-up time was 16.7 (12.4, 25.2) months. At 1 year after mitotane therapy, 10 (83.8%) patients were still in disease-free survival state, with a median mitotane PFS of 27.6 months (95% CI 16.4-not reached). All ACC patients experienced 1-2 grade adverse events after taking mitotane. One patient (8.3%) experienced grade 3 adverse event, including the increasing of alanine aminotransferase and aspartate aminotransferase, as well as anorexia. No grade 4-5 adverse events occurred. The most common adverse events were gastrointestinal symptoms (10 cases), including nausea, vomiting, anorexia, and diarrhea, followed by liver function damage(9 cases) and neurotoxicity(4 cases). Conclusions:Mitotane has shown the prospect of improving the prognosis of ACC patients at high risk of recurrence after surgery. Because of its serious toxic and side effects, it is necessary to monitor its blood concentration to adjust the dosage, and take measures for adverse reactions to ensure the safety of patients.
8.Differences in clinical and pathological features between conventional adrenocortical carcinoma and oncocytic adrenocortical carcinoma
Jiang LIU ; Zhan WANG ; Songchen HAN ; Yi LIU ; Yang ZHAO ; Jianhua DENG ; Yushi ZHANG
Chinese Journal of Urology 2025;46(7):523-528
Objective:To explore the differences in clinicopathological features and prognosis between conventional adrenocortical carcinoma(ACC)and oncocytic ACC.Methods:The clinical and pathological data of patients with conventional ACC and oncocytic ACC who were admitted to Peking Union Medical College Hospital from March 2012 to Fabruary 2025 were retrospectively analyzed. Differences in clinical and pathological characteristics between the two groups were compared. Survival curves were plotted using the Kaplan-Meier method,and differences in survival rates were compared using the log-rank test.Results:The conventional ACC group comprised 137 cases,with a mean age of(47.5 ± 12.6)years and 37.2%(51/137)being male. The oncocytic ACC group included 22 cases,with a mean age of(49.1 ± 15.3)years and 59.1%(13/22)being male. No statistically significant differences were observed in age or gender distribution between the two groups( P > 0.05). The conventional ACC group exhibited a significantly higher prevalence of classic Cushing’s syndrome symptoms compared to the oncocytic ACC group[35.2%(45/128)vs. 5.3%(1/19); χ2 = 6.876, P < 0.01]. Additionally,the proportion of hypertension was higher in the conventional ACC group[49.2%(65/132)vs. 22.2%(4/18); χ2 = 5.319, P < 0.05],whereas the prevalence of adrenal sex characteristics was lower[22.0%(28/127)vs. 63.2%(12/19); χ2 = 14.043, P < 0.01]. The Ki-67 proliferation index was significantly higher in conventional ACC patients[20%(10%,40%)vs. 12%(9%,20%); Z = -2.113, P < 0.05]. Furthermore,the conventional ACC group demonstrated a lower 5-year overall survival rate than the oncocytic ACC group(44.5% vs. 67.3%, P < 0.05). Conclusions:Conventional ACC patients have a higher proportion of Cushing’s symptoms and hypertension,and oncocytic ACC patients have a higher proportion of adrenal sexual characteristics abnormalities. The prognosis of oncocytic ACC is better than that of conventional ACC.
9.Changes in WHO classification of adrenal tumors and new ideas for multi-dimensional diagnosis and treatment
Zhan WANG ; Jianhua DENG ; Xu WANG ; Yi LIU ; Jiayang CHEN ; Yushi ZHANG
Chinese Journal of Surgery 2024;62(11):1001-1007
In 2022, WHO updated the classification and concept of adrenal cortical and medullary tumors. In terms of adrenal cortical tumors, the WHO classification further standardizes the nomenclature of nodular adrenal cortical disease and refines the pathological classification of primary aldosteronism. In terms of adrenal medullary tumors, the WHO classification unifies the concepts of pheochromocytoma and paraganglioma, and reclassifies various concepts, including paraganglioma-like neuroendocrine tumors. The new standards not only cover the clinical manifestations of the disease, but also include other multiple aspects such as the histological origin of the disease, immunohistochemical manifestations, physiological mechanisms of the disease, hereditary susceptibility and prognostic factors. This article intends to explore how to improve the diagnostic and therapeutic level of adrenal tumors.
10.Changes in WHO classification of adrenal tumors and new ideas for multi-dimensional diagnosis and treatment
Zhan WANG ; Jianhua DENG ; Xu WANG ; Yi LIU ; Jiayang CHEN ; Yushi ZHANG
Chinese Journal of Surgery 2024;62(11):1001-1007
In 2022, WHO updated the classification and concept of adrenal cortical and medullary tumors. In terms of adrenal cortical tumors, the WHO classification further standardizes the nomenclature of nodular adrenal cortical disease and refines the pathological classification of primary aldosteronism. In terms of adrenal medullary tumors, the WHO classification unifies the concepts of pheochromocytoma and paraganglioma, and reclassifies various concepts, including paraganglioma-like neuroendocrine tumors. The new standards not only cover the clinical manifestations of the disease, but also include other multiple aspects such as the histological origin of the disease, immunohistochemical manifestations, physiological mechanisms of the disease, hereditary susceptibility and prognostic factors. This article intends to explore how to improve the diagnostic and therapeutic level of adrenal tumors.

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