Nonalcoholic steatohepatitis(NASH)is a chronic metabolic disease characterized by hepatocyte fatty degeneration and ballooning degeneration,and it plays an important role in the progression of hepatic steatosis.Recent studies have shown that immune homeostasis imbalance between T helper 17(Th17)and regulatory T(Treg)cells are closely associated with the pathological process of NASH.Transforming growth factor-β1(TGF-β1)is a key cytokine for regulating the differentiation and proliferation of Th17/Treg cells,and TGF-β1 binds to its receptor and activates the Smad signaling pathway,thereby regulating the immune balance of Th17/Treg cells and the expression of inflammatory factors and participating in the repair of liver inflammation.This article systematically reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in affecting NASH by regulating the immune balance of Th17/Treg cells,in order to provide a theoretical basis for the research on the pathogenesis of NASH and related treatment strategies.

Objective:To analyze the efficacy of delineating the clinical target volume (CTV) following the trajectory of trigeminal nerve branches and elective neck irradiation (ENI) in postoperative intensity-modulated radiotherapy (IMRT) for adenoid cystic carcinoma of head and neck (ACCHN).Methods:In this study, the data of ACCHN patients without distal metastasis who received postoperative radiotherapy after radical surgery at the Ninth People's Hospital of Shanghai Jiaotong University School of Medicine from January 2016 to December 2022 were retrospectively analyzed. Postoperative radiotherapy target zone and intensity-modulated radiotherapy plan for ACCHN were formulated according to the site of primary focus, whether nerve invasion and pathological staging. Kaplan-Meier method was applied to perform survival analysis, while assessing the tumor local control rate and locoregional recurrence pattern under this target zone outlining principle.Results:A total of 309 ACCHN patients were included. With a median follow-up of 49 months, the 5-year local control rate was 93.2%, the 5-year overall survival rate, locoregional recurrence-free survival rate, and distant metastasis-free survival rate were 90.8%, 90.6%, 66.3%, respectively. Twenty-three patients developed locoregional recurrence, including 14 with primary tumor recurrence alone, 5 with regional lymph node recurrence alone, and 4 with both primary and regional lymph node recurrence. Among the patients with primary tumor recurrence, 11 had recurrence related to the trigeminal nerve branches,and 7 had recurrence in the tumor bed or surgical bed region, with no out-of-field recurrence. Among the 9 patients with lymph node recurrence, none had undergone neck dissection.Conclusions:Delineating the CTV following the trigeminal nerve branches in postoperative radiotherapy for ACCHN achieves excellent local control. Elective neck irradiation avoids irradiation of the entire neck lymphatic drainage area with a low regional recurrence rate.

Objective:To evaluate the impact of surgical margin status and pathological subtypes on the prognosis of patients with adenoid cystic carcinoma of the head and neck (ACCHN) who underwent postoperative radiotherapy.Methods:A retrospective analysis was conducted on 309 patients with initially treated, non-metastatic ACCHN who completed postoperative radiotherapy at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. All patients underwent curative (non-palliative) surgery followed by postoperative radiotherapy, with a median dose of 66 Gy (range: 54-70 Gy). The Kaplan-Meier method was used to compare 5-year local recurrence-free survival (LRFS) between R0 (negative margin) and non-R0 resections in patients with initially resectable (T 1-T 4a stage) and initially unresectable (T 4b stage) disease. Univariate and multivariate Cox proportional hazards models were employed to analyze risk factors for local recurrence, with a focus on surgical margin status and pathological subtypes. Results:The median follow-up was 48 months. Of the 309 patients included in the study, 133 were males and 176 were females, with a median age of 51 years (range: 18-77 years). Primary tumors were located in the major salivary glands in 135 cases (including 42 in the parotid gland, 65 in the submandibular gland, and 28 in the sublingual gland) and in the minor salivary glands in 174 cases. The 5-year overall survival, locoregional recurrence-free survival, distant metastasis-free survival, and progression-free survival rates were 91.5%, 90.8%, 66.1%, and 63.9%, respectively. Non-R0 resection was achieved in 177 patients (57.3%). Among initially resectable patients ( n=253), the non-R0 resection rate was 49.0% ( n=124), with only 6 cases (2.4%) experiencing local recurrence (all non-R0 resections). In initially unresectable patients ( n=56), the non-R0 resection rate was as high as 95% ( n=53), with 13 cases (23%) experiencing local recurrence (2 cases in non-R0 resection and 1 case in R0 resection). For initially resectable patients, non-R0 resection significantly reduced the 5-year LRFS rate to 95.2%, compared to 100% in R0 resection patients ( P=0.014). However, multivariate analysis revealed that the solid pathological subtype was an independent risk factor for 5-year LRFS ( HR=7.40, 95% CI: 2.81-19.52, P<0.001), while the surgical margin status was not an independent factor. Conclusions:The combined strategy of surgery and postoperative radiotherapy provides high local control rates for ACCHN patients. Achieving R0 resection is crucial for initially resectable patients, while a comprehensive treatment strategy involving surgery and postoperative radiotherapy remains essential for initially unresectable patients. The solid pathological subtype is the most significant risk factor for local recurrence.

Nonalcoholic steatohepatitis （NASH） is a chronic metabolic disease characterized by hepatocyte fatty degeneration and ballooning degeneration， and it plays an important role in the progression of hepatic steatosis. Recent studies have shown that immune homeostasis imbalance between T helper 17 （Th17） and regulatory T （Treg） cells are closely associated with the pathological process of NASH. Transforming growth factor-β1 （TGF-β1） is a key cytokine for regulating the differentiation and proliferation of Th17/Treg cells， and TGF-β1 binds to its receptor and activates the Smad signaling pathway， thereby regulating the immune balance of Th17/Treg cells and the expression of inflammatory factors and participating in the repair of liver inflammation. This article systematically reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in affecting NASH by regulating the immune balance of Th17/Treg cells， in order to provide a theoretical basis for the research on the pathogenesis of NASH and related treatment strategies.

Metabolic associated fatty liver disease(MAFLD)has a complex pathogenesis,and mitophagy is involved in the development and progression of MAFLD and plays a key role in liver metabolic pathways and signaling networks.Mitophagy is regulated by a variety of pathways,and the PTEN-induced kinase 1(PINK1)/Parkin pathway is considered the main pathway for regulating mitophagy.Mitophagy mediated by the PINK1/Parkin pathway can regulate lipid metabolism,inflammation,and fibrosis and delay the progression of MAFLD.This article reviews the role of mitophagy mediated by the PINK1/Parkin pathway in MAFLD and the research advances in targeted therapy,in order to provide theoretical bases and ideas for the prevention and treatment of MAFLD.

Metabolic associated fatty liver disease(MAFLD)has a complex pathogenesis,and mitophagy is involved in the development and progression of MAFLD and plays a key role in liver metabolic pathways and signaling networks.Mitophagy is regulated by a variety of pathways,and the PTEN-induced kinase 1(PINK1)/Parkin pathway is considered the main pathway for regulating mitophagy.Mitophagy mediated by the PINK1/Parkin pathway can regulate lipid metabolism,inflammation,and fibrosis and delay the progression of MAFLD.This article reviews the role of mitophagy mediated by the PINK1/Parkin pathway in MAFLD and the research advances in targeted therapy,in order to provide theoretical bases and ideas for the prevention and treatment of MAFLD.

Objective:To analyze the efficacy of delineating the clinical target volume (CTV) following the trajectory of trigeminal nerve branches and elective neck irradiation (ENI) in postoperative intensity-modulated radiotherapy (IMRT) for adenoid cystic carcinoma of head and neck (ACCHN).Methods:In this study, the data of ACCHN patients without distal metastasis who received postoperative radiotherapy after radical surgery at the Ninth People's Hospital of Shanghai Jiaotong University School of Medicine from January 2016 to December 2022 were retrospectively analyzed. Postoperative radiotherapy target zone and intensity-modulated radiotherapy plan for ACCHN were formulated according to the site of primary focus, whether nerve invasion and pathological staging. Kaplan-Meier method was applied to perform survival analysis, while assessing the tumor local control rate and locoregional recurrence pattern under this target zone outlining principle.Results:A total of 309 ACCHN patients were included. With a median follow-up of 49 months, the 5-year local control rate was 93.2%, the 5-year overall survival rate, locoregional recurrence-free survival rate, and distant metastasis-free survival rate were 90.8%, 90.6%, 66.3%, respectively. Twenty-three patients developed locoregional recurrence, including 14 with primary tumor recurrence alone, 5 with regional lymph node recurrence alone, and 4 with both primary and regional lymph node recurrence. Among the patients with primary tumor recurrence, 11 had recurrence related to the trigeminal nerve branches,and 7 had recurrence in the tumor bed or surgical bed region, with no out-of-field recurrence. Among the 9 patients with lymph node recurrence, none had undergone neck dissection.Conclusions:Delineating the CTV following the trigeminal nerve branches in postoperative radiotherapy for ACCHN achieves excellent local control. Elective neck irradiation avoids irradiation of the entire neck lymphatic drainage area with a low regional recurrence rate.

Objective:To evaluate the impact of surgical margin status and pathological subtypes on the prognosis of patients with adenoid cystic carcinoma of the head and neck (ACCHN) who underwent postoperative radiotherapy.Methods:A retrospective analysis was conducted on 309 patients with initially treated, non-metastatic ACCHN who completed postoperative radiotherapy at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. All patients underwent curative (non-palliative) surgery followed by postoperative radiotherapy, with a median dose of 66 Gy (range: 54-70 Gy). The Kaplan-Meier method was used to compare 5-year local recurrence-free survival (LRFS) between R0 (negative margin) and non-R0 resections in patients with initially resectable (T 1-T 4a stage) and initially unresectable (T 4b stage) disease. Univariate and multivariate Cox proportional hazards models were employed to analyze risk factors for local recurrence, with a focus on surgical margin status and pathological subtypes. Results:The median follow-up was 48 months. Of the 309 patients included in the study, 133 were males and 176 were females, with a median age of 51 years (range: 18-77 years). Primary tumors were located in the major salivary glands in 135 cases (including 42 in the parotid gland, 65 in the submandibular gland, and 28 in the sublingual gland) and in the minor salivary glands in 174 cases. The 5-year overall survival, locoregional recurrence-free survival, distant metastasis-free survival, and progression-free survival rates were 91.5%, 90.8%, 66.1%, and 63.9%, respectively. Non-R0 resection was achieved in 177 patients (57.3%). Among initially resectable patients ( n=253), the non-R0 resection rate was 49.0% ( n=124), with only 6 cases (2.4%) experiencing local recurrence (all non-R0 resections). In initially unresectable patients ( n=56), the non-R0 resection rate was as high as 95% ( n=53), with 13 cases (23%) experiencing local recurrence (2 cases in non-R0 resection and 1 case in R0 resection). For initially resectable patients, non-R0 resection significantly reduced the 5-year LRFS rate to 95.2%, compared to 100% in R0 resection patients ( P=0.014). However, multivariate analysis revealed that the solid pathological subtype was an independent risk factor for 5-year LRFS ( HR=7.40, 95% CI: 2.81-19.52, P<0.001), while the surgical margin status was not an independent factor. Conclusions:The combined strategy of surgery and postoperative radiotherapy provides high local control rates for ACCHN patients. Achieving R0 resection is crucial for initially resectable patients, while a comprehensive treatment strategy involving surgery and postoperative radiotherapy remains essential for initially unresectable patients. The solid pathological subtype is the most significant risk factor for local recurrence.

Objective:To investigate the optimal treatment modalities and prognostic factors of adenoid cystic carcinoma of the head and neck salivary gland.Methods:From January 2016 to December 2018, clinical data of 166 patients with adenoid cystic carcinoma of the head and neck salivary gland who received postoperative radiotherapy at Department of Radiation Oncology of the Ninth People′s Hospital of Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The survival analysis was performed by Kaplan-Meier method. Univariate prognostic analysis was conducted by log-rank test. Multivariate prognostic analysis was carried out by Cox proportional hazard regression model.Results:Among 166 enrolled patients, 70 cases were male and 96 female with an average age of 53 years (18 to 71 years). The median follow-up time was 31.2 months (8.6-63.1 months). Sixty-six patients underwent radical surgery (extended resection across the anatomical areas outside the tumor bed, pursuing negative margins of various resections), and the remaining 100 patients underwent conservative surgery (only extended resection of lesions, not pursuing negative nerve resection margins). The median dose of postoperative radiotherapy was 66 Gy (54-70 Gy). Seventy-three patients were treated with TP regime due to positive or close margins and 9 cases of cervical lymph node metastasis. The 3-and 5-year overall survival (OS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS) rates were 95% and 95%, 93% and 93%, 74% and 66%, 73% and 65%, respectively. Seven patients experienced primary lesion recurrence, 5 cases of regional lymph node recurrence and 38 cases of distant metastasis. T 3-T 4 stage, lymph nodes (+ ), stage IV, solid pathologic subtype, Ki-67≥10% and perineural invasion were associated with worse PFS and DMFS. Multivariate analysis demonstrated that only solid pathologic subtype was the independent prognostic factor of OS, LRRFS, PFS and DMFS. Conclusions:The local control rate of salivary gland adenoid cystic carcinoma can be improved by postoperative intensity-modulated radiotherapy (IMRT) with a recommended dose of ≥66 Gy. Solid pathologic subtype is the most important adverse prognostic factor.

Objective To assess the efficacy and safety of post operative adjuvant concurrent chemoradiotherapy for patients with high-risk salivary gland tumors (SGT).Methods Fifty-two patients with moderate or high malignant pathological stage complicated with locally advanced stage Ⅲ/ⅣA±positive margin/close margin admitted to Shanghai Ninth People's Hospital from 2016 to 2018 were enrolled in this study.Among them,35 patients were male and 17 female with a median age of 55.5 years old (range:21-73 years old).All 52 patients were treated with intensity-modulated radiotherapy and concurrent chemotherapy.Patients with adeno carcinoma of the salivary gland receives concurrent chemotherapy with TP regimen.Patients with lympho epithelial cancer and squamous cell carcinoma were treated with cisplatin regimen.Results Forty-seven patients (90％) completed two cycles of concurrent chemotherapy,and five patients (10％) completed one cycle of concurrent chemotherapy.The median follow-up time was 15.7 months (3.2-34.8 months).The 2-year disease-free survival (DFS) and overall survival (OS) rates were 74％ and 98％.Three patients experienced regional lymph recurrence and 6 cases had distant metastasis.Grade Ⅲ oral mucositis was observed in 30 patients.Grade Ⅲ dermatitis occurred in 5 cases.Only one patient experienced Grade Ⅳ neutropenia,and 2 patients developed Grade Ⅲ neutropenia.DFS was positively correlated with the cycle of postoperative adjuvant concurrent chemotherapy (P=0.006).Conclusions Patients with high-risk SGT can obtain higher 2-year DFS and OS rates and tolerable adverse events after postoperative concurrent chemoradiotherapy.Nevertheless,the long-term outcomes remain to be validated by randomized controlled clinical trials.