1.Clinical application of Mimics software system to three-dimensional reconstruction to guide thoracoscopic anatomic pulmonary segmentectomy
Shuang LI ; Yijun SHI ; Guowen DING ; Yangyong SUN ; Benbo LÜ ; ; Jianchao LIU ; Jingfeng ZHU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(01):59-64
		                        		
		                        			
		                        			Objective    To investigate the clinical effect of 3D computed tomography bronchial bronchography and angiography (3D-CTBA) and guidance of thoracoscopic anatomic pulmonary segmentectomy by Mimics software system. Methods    A retrospective analysis was performed on patients who underwent thoracoscopic segmentectomy in the Department of Thoracic Surgery of Affiliated People's Hospital of Jiangsu University from June 2020 to December 2022. The patients who underwent preoperative 3D-CTBA using Materiaise's interactive medical image control system (Mimics) were selected as an observation group, and the patients who did not receive 3D-CTBA were selected as a control group. The relevant clinical indicators were compared between the two groups. Results    A total of 59 patients were included, including 29 males and 30 females, aged 25-79 years. There were 37 patients in the observation group, and 22 patients in the control group. The operation time (163.0±48.7 min vs. 188.8±43.0 min, P=0.044), intraoperative blood loss [10.0 (10.0, 20.0) mL vs. 20.0 (20.0, 35.0) mL, P<0.001], and preoperative puncture localization rate (5.4% vs. 31.8%, P=0.019) in the observation group were better than those in the control group. There was no statistically significant difference in the thoracic tube placement time, thoracic fluid drainage volume, number of intraoperative closure nail bin, postoperative hospital stay, or postoperative air leakage incidence (P>0.05) between the two groups. Conclusion    For patients who need to undergo anatomical pulmonary segmentectomy, using Mimics software to produce 3D-CTBA before surgery can help accurately identify pulmonary arteriovenous anatomy, reduce surgical time and intraoperative blood loss, help to determine the location of nodules and reduce invasive localization before surgery, and alleviate patients' pain, which is worthy of clinical promotion.
		                        		
		                        		
		                        		
		                        	
2.Development and predictive efficiency test of a risk assessment tool for chemotherapy induced nausea and vomiting after transcatheter arterial chemoembolization in patients with primary liver cancer
Hui QI ; Guowen YIN ; Qingyu XU ; Hui ZHANG ; Weidi TAI ; Zhengjing LI
Chinese Journal of Practical Nursing 2024;40(8):596-603
		                        		
		                        			
		                        			Objective:To develop a risk assessment tool for chemotherapy induced nausea and vomiting after transcatheter arterial chemoembolization in patients with primary liver cancer, and to verify its predictive efficiency, so as to provide reference for risk assessment and nursing intervention of nausea and vomiting in patients with primary liver cancer.Methods:A cross-sectional survey was used. The risk assessment tool was compiled by using literature analysis, Delphi expert consultation and analytic hierarchy process. 153 patients with primary liver cancer who underwent transcatheter arterial chemoembolization in the Department of Intervention, Jiangsu Cancer Hospital from May 2022 to April 2023 were selected for assessment by using convenience sampling method. Receiver operating characteristic curve, sensitivity, specificity and Youden index were used to test the prediction efficiency of risk assessment tools.Results:Among 153 patients, there were 78 males, 75 females, aged (48.44 ± 7.76) years old. The expert positive coefficient of the three rounds of inquiry letters was all 100%, the expert authority coefficient was 0.936, 0.950 and 0.960 respectively, and the Kendall harmony coefficient was 0.490, 0.327 and 0.414 respectively (all P<0.01). The risk assessment tool for chemotherapy induced nausea and vomiting after transcatheter arterial chemoembolization in patients with primary liver cancer included 14 items. The results of prediction efficiency analysis showed that the area under the receiver operating characteristic curve was 0.938 (95% CI 0.903-0.974, P<0.01). When the cut-off score was 56.2, the sensitivity, specificity and Youden index of the risk assessment tool were 0.926, 0.881 and 0.807, which had the best prediction efficiency. Conclusions:The risk assessment tool for chemotherapy induced nausea and vomiting after transcatheter arterial chemoembolization in patients with primary liver cancer has high scientificity, predictive efficiency and practicability, and is suitable for the risk assessment for chemotherapy induced nausea and vomiting after transcatheter arterial chemoembolization in patients with primary liver cancer in China.
		                        		
		                        		
		                        		
		                        	
3.Echocardiographic manifestations of infective endocarditis complicated with valve damage in children
Liyuan XU ; Hongju ZHANG ; Jingya LI ; Yan SUN ; Jiao YANG ; Li XUE ; Guowen LIU ; Yifei HU ; Ning MA
Chinese Journal of Medical Imaging Technology 2024;40(7):968-972
		                        		
		                        			
		                        			Objective To observe the echocardiographic manifestations of infective endocarditis(IE)complicated with valve damage in children.Methods Totally 104 children with IE were retrospectively enrolled and divided into non-damage group(n=34),mild damage group(n=39)and dysfunction group(n=31)according to whether complicated with valve damage and damage's degree.The general and echocardiographic data were compared among groups,and the echocardiographic characteristics of IE complicated with valve damage in children were analyzed.Results Significant difference of the proportion of combining with other congenital heart diseases(excluding bicuspid aortic malformations),the incidence of embolization events during hospital stay,also of endocarditis of left cardiac system were found among groups(all P<0.05).Pairwise comparison showed that in non-damage group,the proportion of combining with other congenital heart diseases was higher,while the incidence of endocarditis of left cardiac system was lower than those in both mild damage group and dysfunction group(all P<0.05).The incidence of embolization events during hospital stay in non-damage group was lower than that in dysfunction group(P<0.05).Among 70 cases of IE complicated with valve damage,mitral valve(30/70,42.86%)was the most common involved valve,mostly presented as valve stenosis(63/70,90.00%).No significant difference of valve involvement site,valve structural lesions nor the incidence of valve stenosis was found between mild damage group and dysfunction group(all P>0.05).Conclusion IE complicated with valve damage in children mostly involved left cardiac system,and the risk of embolization events was higher than that of IE children without valve damage.Echocardiography could be used as an important method for evaluating the site of valve involvement and the degree of damage.
		                        		
		                        		
		                        		
		                        	
4.Observation on isolated bicuspid aortic valve in children using echocardiography
Jiao YANG ; Ning MA ; Liyuan XU ; Li XUE ; Yan SUN ; Hongju ZHANG ; Guowen LIU ; Ruijuan SU
Chinese Journal of Medical Imaging Technology 2024;40(7):978-981
		                        		
		                        			
		                        			Objective To observe the manifestations of isolated bicuspid aortic valve(i-BAV)in children using echocardiography.Methods Echocardiographic data of 79 children with i-BAV were retrospectively analyzed,and classification of i-BAV was performed.The patients were divided into complication group(n=50)and non-complication group(n=29)according to the existence of valve and/or aortic involvement or not,and echocardiographic parameters were compared between groups.Results After adjusting body surface area(BSA),in complication group,left ventricular end-systolic diameter/BSA was lower,while left ventricular myocardial mass index group was higher than those in non-complication group(both P<0.05).Type 0 i-BAV was found in 22 cases,with lat subtype as the most common ones(18/22,81.82%),while Type Ⅰ was observed in 57 cases with L-R subtype as the most common ones(39/57,68.42%).The most common subtype in complication group was also Type Ⅰ L-R(31/50,62.00%),with incidence of valve involvement of 90.00%(45/50),mainly including mild aortic stenosis and/or incompetence(37/45,82.22%),and incidence of aorta involvement of 24.00%(12/50),all with type Ⅰ or Ⅱ aortic widening.Conclusion The most common subtype of i-BAV in children was type Ⅰ L-R,with mild valve damage as the main complication and possibility of left ventricular myocardial remodeling.
		                        		
		                        		
		                        		
		                        	
5.Preparation and preliminary of astragalus polysaccharide synbiotics and its effect on growth performance of calves
Lanzhuo WANG ; Chenxi XUE ; Jun CHEN ; Xinwei LI ; Guowen LIU
Chinese Journal of Veterinary Science 2024;44(8):1821-1830
		                        		
		                        			
		                        			In this study,freeze-drying methods was used to prepare astragalus polysaccharide synbi-otic powder.The optimized freeze-dried protective agent formulation using response surface meth-odology in this study was 17.99%skimmed milk powder,7.26%sucrose,8.04%galactooligosac-charides,and 9.64%astragalus polysaccharide,and the remaining amount was distilled water.The survival rate of lactic acid bacteria in the prepared bacterial powder was 88.06%.A calf feeding ex-periment was conducted over 28 days with thirty healthy newborn calves with similar age,the calves were randomly assigned to either control group and the astragalus polysaccharide synbiotic group,each comprising 15 calves.The astragalus polysaccharide synbiotic group received a supple-ment of astragalus polysaccharide in addition to their regular feed.Compared to the control group,the results showed that:(1)Astragalus polysaccharide synbiotics significantly increased the aver-age daily gain(ADG)of calves and decreased the fecal score and diarrhea rate in calves.(2)By tes-ting the immunological indexes,we found that astragalus polysaccharide synbiotics significantly in-creased the serum level of IgA,IgG,IgM,IL-2 and IL-10,and decreased the level of IL-6 and TNF-α.(3)Astragalus polysaccharide synbiotics notably enhanced the Chao1,Sobs,and Shannon indi-ces,while reducing the Simpson index.At the phylum level,astragalus polysaccharide synbiotics group showed a significant increase in the relative abundance of Cyanobacterium and Firmicutes,and a decrease in Proteobacteria.At the genus level,the relative abundance of Esche-richia-Shigella in astragalus polysaccharide synbiotic group significantly decreased.Whereas norank_f__norank_o__Clostridia_UCG-014 and Butyricicoccus significantly increased.In conclu-sion,this study successfully formulated an astragalus polysaccharide synbiotic powder.The powder can significantly promote the growth of calves,enhance immune function,improve the structure of gut microbiota,and reduce the incidence of calf diarrhea.
		                        		
		                        		
		                        		
		                        	
6.Expert consensus on surgical treatment of oropharyngeal cancer
China Anti-Cancer Association Head and Neck Oncology Committee ; China Anti-Cancer Association Holistic Integrative Oral Cancer on Preventing and Screen-ing Committee ; Min RUAN ; Nannan HAN ; Changming AN ; Chao CHEN ; Chuanjun CHEN ; Minjun DONG ; Wei HAN ; Jinsong HOU ; Jun HOU ; Zhiquan HUANG ; Chao LI ; Siyi LI ; Bing LIU ; Fayu LIU ; Xiaozhi LV ; Zheng-Hua LV ; Guoxin REN ; Xiaofeng SHAN ; Zhengjun SHANG ; Shuyang SUN ; Tong JI ; Chuanzheng SUN ; Guowen SUN ; Hao TIAN ; Yuanyin WANG ; Yueping WANG ; Shuxin WEN ; Wei WU ; Jinhai YE ; Di YU ; Chunye ZHANG ; Kai ZHANG ; Ming ZHANG ; Sheng ZHANG ; Jiawei ZHENG ; Xuan ZHOU ; Yu ZHOU ; Guopei ZHU ; Ling ZHU ; Susheng MIAO ; Yue HE ; Jugao FANG ; Chenping ZHANG ; Zhiyuan ZHANG
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(11):821-833
		                        		
		                        			
		                        			With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth>3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.
		                        		
		                        		
		                        		
		                        	
7.The E3 ubiquitin ligase NEDD4-1 protects against acetaminophen-induced liver injury by targeting VDAC1 for degradation.
Yiwei ZHU ; Lin LEI ; Xinghui WANG ; Linfang CHEN ; Wei LI ; Jinxia LI ; Chenchen ZHAO ; Xiliang DU ; Yuxiang SONG ; Wenwen GAO ; Guowen LIU ; Xinwei LI
Acta Pharmaceutica Sinica B 2023;13(4):1616-1630
		                        		
		                        			
		                        			Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.
		                        		
		                        		
		                        		
		                        	
8.The clinical value of the New England spinal metastases score system in predicting the survival of patients with spinal metastases
Bingshan YAN ; Jingyu ZHANG ; Yancheng LIU ; Hong ZHANG ; Li YANG ; Jikai LI ; Xiuchun YU ; Guochuan ZHANG ; Guowen WANG ; Yu ZHANG ; Yongcheng HU
Chinese Journal of Orthopaedics 2022;42(20):1329-1339
		                        		
		                        			
		                        			Objective:To evaluate the clinical value of the New England spinal metastasis score (NESMS) in predicting the prognosis of patients with spinal metastases by retrospectively analyzing the medical records of multicenter spinal metastases in China.Methods:The data of 179 patients with spinal metastases from January 2008 to December 2018 were retrospectively collected. There were 108 males (60.3%) and 71 females (39.7%) with an average age of 59.79±10.88 years old (range 27-84 years). The patient demographic characteristics, primary tumor type, spinal metastases and segments, vertebral pathological fractures, neurological Frankel classification, physical function status, Karnofsky performance scale (KPS), visual analogue score (VAS), the spinal instability neoplastic score (SINS), modified Bauer score, NESMS score, Tomita score and modified Tokuhashi score were collected. The clinical value of NESMS score, Tomita score and modified Tokuhashi score in predicting the survival of patients with spinal metastases were compared. The independent factors affecting survival in these patients were analyzed by Cox proportional hazards regression model.Results:Among the 179 patients, the peak incidence of spinal metastases was in the age group of 61-75 years (45.3%, 81/179) of all patients. Lung cancer was the most common primary tumor (46.9%, 84/179). 40.8% (73/179) of patients had multi-segment metastasisand thoracic spine was the most common site with single-site metastasis (26.3%, 47/179). 28.5% (51/179) of the patients had visceral metastases and 52.0% (93/179) of the patients had extraspinal bone metastases. 31.3% (56/179) of the patients had pathological fractures of the involved vertebral bodies.114 patients received surgical treatment (63.4%). The mortality rates in 3-months, 6-months and 1-year were 22.4% (40/179), 51.4% (92/179) and 77.1% (138/179), respectively. The median survival time of patients with NESMS score of 0-3 was 3, 4, 8, and 10 months respectively with the mean survival time was 3.60±2.10, 6.77±3.39, 9.69±5.71 and 10.53±6.25 months. The 1-year mortality rates were 100% (13/13), 87.5% (42/48), 71.6% (63/88) and 66.7% (20/30) respectively. The consistency of NESMS score, Tomita score and modified Tokuhashi score in predicting survival of all patients was 0.63, 0.58 and 0.55, respectively. For patients with spinal metastases, the NESMS score was better than the Tomita score and modified Tokuhashi score in predicting survival at 3-months (AUC=1.00, 0.63, 0.42) and 6-months (AUC=0.71, 0.63, 0.45). But the accuracy of Tomita score was best in predicting survival at 1-year (AUC=0.66, 0.61, 0.38). Multivariate Cox proportional hazards regression model analysis showed that growth rate of primary tumor, neurological function Frankel score, albumin level and surgical treatment were independent factors affecting the survival time of patients with spinal metastases ( P<0.05). Conclusion:The consistency and accuracy of NESMS score in predicting survival of patients with spinal metastases are better than Tomita score and modified Tokuhashi score, especially in predicting 3- and 6-month survival. The growth rate of primary tumor, Frankel classification, albumin level and surgical treatment were independent factors affecting the survival time of patients with spinal metastases.
		                        		
		                        		
		                        		
		                        	
9.The trend of clinical and pathological characteristics and surgical treatment in patients with spinal metastases: A multicenter retrospective study
Bingshan YAN ; Yancheng LIU ; Hong ZHANG ; Li YANG ; Jikai LI ; Xiuchun YU ; Guochuan ZHANG ; Zhaoming YE ; Guowen WANG ; Yu ZHANG ; Yongcheng HU
Chinese Journal of Orthopaedics 2022;42(8):471-481
		                        		
		                        			
		                        			Objective:To retrospectively analyze the patients with spinal metastases who received surgical intervention and summarize the evolution of their clinical and pathological characteristics and surgical methods.Methods:The data of 703 patients with spinal metastases from January 2007 to December 2018 were collected retrospectively. There were 395 males (56.19%, 395/703) and 308 females (43.81%, 308/703) with an average age of 58.14±11.46 years (range 13-84 years). According to the degree of invasion and thoroughness of tumor resection, the surgical methods could be divided into minimally invasive surgery, decompression surgery, separation surgery, piecemeal resection and total en-bloc spondylectomy surgery. The operative methods were minimally invasive surgery in 89 cases (12.66%), decompression surgery in 96 cases (13.66%), separation surgery in 303 cases (43.10%), piecemeal resection in 182 cases (25.89%) and total en-bloc spondylectomy in 33 cases (4.69%). To analyze the trend of the clinical, pathological types and surgical treatment of patients with spinal metastases over the years, and determine the relevant factors affecting the decision-making of surgical methods by multivariate logistic regression.Results:The ratio of male to female was 1.28:1. 39.54% (278/703) of patients with single-segment involvement in 703 patients, 24.04% (169/703) of patients with double-segment metastasis and 36.42% (256/703) of patients with multi-segment metastasis. The most common type of primary tumor was lung cancer (34.57%, 243/703), followed by breast cancer (8.25%, 58/703), myeloma (8.11%, 57/703), gastrointestinal tumor (6.82%, 48/703) and renal malignant tumor (6.40%, 45/703). From 2007 to 2018, there was no significant difference in the percentage change of different age, gender and primary tumor source composition (age: χ 2=14.01, P=0.233; gender: χ 2=35.73, P=0.341; primary tumor: χ 2=120.09, P=0.074). The percentage of patients with sacrococcygeal metastasis decreased from 20.00% in 2008 to 1.89% in 2017 and the difference was statistically significant (χ 2=8.09, P=0.005). The percentage of patients with multi-level metastasis increased from 26.67% in 2008 to 52.83% in 2017, and the difference was statistically significant (χ 2=7.23, P=0.007). The percentage of patients with minimally invasive surgery decreased from 25.00% in 2007 to 5.88% in 2018, and the percentage of patients with segmented resection decreased from 53.33% in 2008 to 10.29% in 2018. The proportion of the two surgical methods showed a significant downward trend, and the differences were statistically significant (minimally invasive surgery: χ 2=1.46, P=0.026; segmented resection surgery: χ 2=19.56, P<0.001). The percentage of patients undergoing separation surgery increased from 13.33% in 2008 to 64.71% in 2018, and the proportion of patients undergoing total en-bloc spondylectomy increased from 0 in 2007 to 10.29% in 2018. Both surgical methods showed a significant growth trend and the differences were statistically significant (separation surgery: χ 2=27.09, P<0.001; χ 2=4.16, P=0.042). Multivariate Logistic regression analysis showed that age, metastatic site, number of metastatic segments, pathological vertebral fractures, Frankel grade, SINS score and VAS score were independent factors influencing surgical decision-making ( P<0.05). Conclusion:With different time and age, the invasiveness and thoroughness of surgery are increasing, which shows that the percentage of patients who underwent separation surgery and to-tal en-bloc spondylectomy is significantly increasing. Age, metastatic site, number of metastatic segments, pathological vertebral fractures, Frankel grade, SINS score and VAS score are independent factors affecting surgical decision-making.
		                        		
		                        		
		                        		
		                        	
10.Nuciferine protects against high-fat diet-induced hepatic steatosis and insulin resistance via activating TFEB-mediated autophagy-lysosomal pathway.
Xiliang DU ; Chiara DI MALTA ; Zhiyuan FANG ; Taiyu SHEN ; Xiaodi NIU ; Meng CHEN ; Bo JIN ; Hao YU ; Lin LEI ; Wenwen GAO ; Yuxiang SONG ; Zhe WANG ; Chuang XU ; Zhijun CAO ; Guowen LIU ; Xinwei LI
Acta Pharmaceutica Sinica B 2022;12(6):2869-2886
		                        		
		                        			
		                        			Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.
		                        		
		                        		
		                        		
		                        	
            

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