1.NLRP6 overexpression improves nonalcoholic fatty liver disease by promoting lipid oxidation and decomposition in hepatocytes through the AMPK/CPT1A/PGC1A pathway.
Qing SHI ; Suye RAN ; Lingyu SONG ; Hong YANG ; Wenjuan WANG ; Hanlin LIU ; Qi LIU
Journal of Southern Medical University 2025;45(1):118-125
OBJECTIVES:
To investigate the regulatory role of nucleotide-bound oligomerized domain-like receptor containing pyrin-domain protein 6 (NLRP6) in liver lipid metabolism and non-alcoholic fatty liver disease (NAFLD).
METHODS:
Mouse models with high-fat diet (HFD) feeding for 16 weeks (n=6) or with methionine choline-deficient diet (MCD) feeding for 8 weeks (n=6) were examined for the development of NAFLD using HE and oil red O staining, and hepatic expressions of NLRP6 were detected with RT-qPCR, Western blotting, and immunohistochemical staining. Cultured human hepatocytes (LO2 cells) with adenovirus-mediated NLRP6 overexpression or knock-down were treated with palmitic acid (PA) in the presence or absence of compound C (an AMPK inhibitor), and the changes in cellular lipid metabolism were examined by measuring triglyceride, ATP and β-hydroxybutyrate levels and using oil red staining, RT-qPCR, and Western blotting.
RESULTS:
HFD and MCD feeding both resulted in the development of NAFLD in mice, which showed significantly decreased NLRP6 expression in the liver. In PA-treated LO2 cells, NLRP6 overexpression significantly decreased cellular TG content and lipid deposition, while NLRP6 knockdown caused the opposite effects. NLRP6 overexpression in PA-treated LO2 cells also increased mRNA and protein expressions of PGC1A and CPT1A, levels of ATP and β-hydroxybutyrate, and the phosphorylation level of AMPK pathway; the oxidative decomposition of lipids induced by Ad-NLRP6 was inhibited by the use of AMPK inhibitors.
CONCLUSIONS
NLRP6 overexpression promotes lipid oxidation and decomposition through AMPK/CPT1A/PGC1A to alleviate lipid deposition in hepatocytes.
Non-alcoholic Fatty Liver Disease/metabolism*
;
Animals
;
Hepatocytes/metabolism*
;
Lipid Metabolism
;
Mice
;
Humans
;
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
;
AMP-Activated Protein Kinases/metabolism*
;
Carnitine O-Palmitoyltransferase/metabolism*
;
Diet, High-Fat
;
Male
;
Mice, Inbred C57BL
;
Signal Transduction
2.Value of late gadolinium enhancement cardiac MRI in predicting ventricular arrhythmia in patients with ICD
Lingyu SONG ; Jian LI ; Chuang ZHANG ; Manman YANG ; Guoxing ZHANG ; Xiaoya SU ; Xiangmin SHI
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(2):132-135
Objective To investigate the application value of late gadolinium enhancement(LEG)at cardiac MRI in predicting ventricular arrhythmia(VA)events in patients after implantation of ICD.Methods A retrospective analysis was performed on 16 patients at high risk of sudden cardi-ac death after ICD implantation and LEG examination in the First and the Sixth Medical Centers of Chinese PLA General Hospital from June 2020 to March 2024.According the occurrence of VA events receiving appropriate ICD therapy during the follow-up period,they were divided into post-operative VA group(7 cases)and non-VA group(9 cases).The correlation of clinical baseline fea-tures and LEG features with VA events was analyzed.Results The ratios of transmural enhance-ment and myocardial medium enhancement were obviously higher in the VA group than the non-VA group(71.4%vs 11.1%,P=0.035;85.7%vs 22.2%,P=0.041).Multivariate logistic regres-sionanalysis showed that transmural enhancement(OR=5.000,95%CI:0.150-166.589,P=0.368)and myocardial medium enhancement(OR=7.000,95%CI:0.217-226.005,P=0.272)were not independent factors influencing VA occurrence.ROC curve analysis indicated that the combined prediction of transmural enhancement and myocardial media enhancement and the pre-diction of transmural enhancement alone had better diagnostic efficacy(P<0.05).Conclusion LEG has clinical value in predicting postoperative VA events in patients after ICD implantation.
3.Analysis of the Thought of"Mutual Reference of Pulse and Time"of Yi Dagen,a Physician of the Xujiang School in Ming Dynasty
Yuecheng SUN ; Lingyu WU ; Yongmei SONG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(10):1327-1332
Yi Dagen was a famous physician of Xujiang School in Ming Dynasty.In the process of syndrome differentiation and treatment,Yi Dagen attached great importance to pulse diagnosis and paid attention to the influence of time factors.His theory was based on"Yin and Yang having time rules and coordinating with pulse"in Basic Questions:The subtlety of pulse diagnosis,emphasizing the mutual reference of pulse and time,reflecting the fundamental principle of"correspondence between nature and man"in traditional Chinese medicine.The thought of mutual reference of pulse and time is mainly reflected in two levels:one is to guide syndrome differ-entiation,which can be summarized as referring to midnight-midday ebb flow to identify the location of the disease,referring to the four-season and five-viscus pulse method to identify the cause of the disease,referring to the north-south governance to identify the nature of the disease,and choosing the time to diagnose the pulse to identify the disease situation;the second is the whole process of syndrome differentiation and treatment,including pulse and time diagnosis and treatment according to the time.The idea of mutual ref-erence of pulse and time plays an important guiding role in current clinical work.In the future,wearable pulse diagnosis equipment and intelligent monitoring technology can be combined to build a dynamic pulse analysis system to realize the real-time and precise applica-tion of the"mutual reference of pulse and time"theory.
4.Analysis of the Thought of"Mutual Reference of Pulse and Time"of Yi Dagen,a Physician of the Xujiang School in Ming Dynasty
Yuecheng SUN ; Lingyu WU ; Yongmei SONG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(10):1327-1332
Yi Dagen was a famous physician of Xujiang School in Ming Dynasty.In the process of syndrome differentiation and treatment,Yi Dagen attached great importance to pulse diagnosis and paid attention to the influence of time factors.His theory was based on"Yin and Yang having time rules and coordinating with pulse"in Basic Questions:The subtlety of pulse diagnosis,emphasizing the mutual reference of pulse and time,reflecting the fundamental principle of"correspondence between nature and man"in traditional Chinese medicine.The thought of mutual reference of pulse and time is mainly reflected in two levels:one is to guide syndrome differ-entiation,which can be summarized as referring to midnight-midday ebb flow to identify the location of the disease,referring to the four-season and five-viscus pulse method to identify the cause of the disease,referring to the north-south governance to identify the nature of the disease,and choosing the time to diagnose the pulse to identify the disease situation;the second is the whole process of syndrome differentiation and treatment,including pulse and time diagnosis and treatment according to the time.The idea of mutual ref-erence of pulse and time plays an important guiding role in current clinical work.In the future,wearable pulse diagnosis equipment and intelligent monitoring technology can be combined to build a dynamic pulse analysis system to realize the real-time and precise applica-tion of the"mutual reference of pulse and time"theory.
5.Value of late gadolinium enhancement cardiac MRI in predicting ventricular arrhythmia in patients with ICD
Lingyu SONG ; Jian LI ; Chuang ZHANG ; Manman YANG ; Guoxing ZHANG ; Xiaoya SU ; Xiangmin SHI
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(2):132-135
Objective To investigate the application value of late gadolinium enhancement(LEG)at cardiac MRI in predicting ventricular arrhythmia(VA)events in patients after implantation of ICD.Methods A retrospective analysis was performed on 16 patients at high risk of sudden cardi-ac death after ICD implantation and LEG examination in the First and the Sixth Medical Centers of Chinese PLA General Hospital from June 2020 to March 2024.According the occurrence of VA events receiving appropriate ICD therapy during the follow-up period,they were divided into post-operative VA group(7 cases)and non-VA group(9 cases).The correlation of clinical baseline fea-tures and LEG features with VA events was analyzed.Results The ratios of transmural enhance-ment and myocardial medium enhancement were obviously higher in the VA group than the non-VA group(71.4%vs 11.1%,P=0.035;85.7%vs 22.2%,P=0.041).Multivariate logistic regres-sionanalysis showed that transmural enhancement(OR=5.000,95%CI:0.150-166.589,P=0.368)and myocardial medium enhancement(OR=7.000,95%CI:0.217-226.005,P=0.272)were not independent factors influencing VA occurrence.ROC curve analysis indicated that the combined prediction of transmural enhancement and myocardial media enhancement and the pre-diction of transmural enhancement alone had better diagnostic efficacy(P<0.05).Conclusion LEG has clinical value in predicting postoperative VA events in patients after ICD implantation.
6.Construction of a predictive model for postoperative subsyndromal delirium in elderly patients undergoing abdominal surgery
Shunli CHEN ; Yan LIU ; Jing CHEN ; Lingyu TANG ; Ru SONG ; Luyao CAI ; Silin ZHENG
Chinese Journal of Nursing 2024;59(16):2001-2008
Objective To analyze the influencing factors of postoperative subsyndromal delirium in elderly patients undergoing abdominal surgery,and to develop a nomogram risk prediction model.Methods A convenience sampling method was used to select 497 elderly patients who underwent abdominal surgery in a tertiary hospital in Sichuan Province from February to October 2022.The risk prediction model and nomograms model were constructed using Logistic regression analysis and R software.The area under the subject's working characteristic curve(AUC)and Hosmer-Lemshow test were used to evaluate the discrimination and calibration of the model.Results The results of Logistic regression showed that age(OR=1.066),functional activities(OR=1.143),patient controlled intravenous analgesia(OR=5.811),transanal drainage tube(OR=2.276)and postoperative blood transfusion(OR=4.322)were independent influences on the occurrence of postoperative subsyndromal delirium.The p-values of the prediction model in both the training and validation sets were greater than 0.05;the area under the ROC curves were 0.734 and 0.691;the model was presented in the form of nomogram.Conclusion The prediction model developed in this study has good discrimination and accuracy.It can be used to assist clinical staff in identifying patients at high risk of developing postoperative subsyndromal delirium and provide the reference for developing preventive and intervention measures.
7.Effect of EPDR1 on hepatocyte lipid deposition
Guifang WANG ; Xuebing CHANG ; Laying HU ; Lu LIU ; Yali HUANG ; Lingyu SONG ; Yuxia ZHOU ; Bing GUO
Chinese Journal of Pathophysiology 2024;40(7):1205-1212
AIM:This study aims to examine the ependymin-related protein 1(EPDR1)expression in various tissues from wild-type C57BL/6 mice and type 2 diabetes(db/db)mice.The impact of EPDR1 on lipid accumulation in al-pha mouse liver 12(AML12)hepatocytes was also investigated.METHODS:Western blot was used to detect EPDR1 protein expression in the heart,liver,spleen,lung,kidney,gastrocnemius,brown adipose and brain tissues of C57BL/6 mice.Western blot and immunohistochemical(IHC)staining were also used to compare EPDR1 protein expression in the liver,gastrocnemius muscle,heart and kidney tissues of db/db and C57BL/6 mice.To develop an AML12 cell lipid deposi-tion model,palmitic acid(PA)+oleic acid(OA)was used,and the cells were transfected with adenovirus overexpressing EPDR1 or treated with exogenous recombinant EPDR1 protein(rEPDR1).ELISA was conducted to determine intracellu-lar triglyceride(TG)content,and oil red O staining was employed to assess the effect of EPDR1 on lipid accumulation in AML12 cells.RESULTS:Western blot and IHC staining results revealed that EPDR1 was widely expressed in various tis-sues of wild-type mice,with the liver exhibiting the highest protein expression level.However,EPDR1 expression was down-regulated in the liver,gastrocnemius muscle,heart and kidney tissues in diabetic db/db mice compared with wild-type mice.Oil red O staining revealed that overexpression of EPDR1 in AML12 liver cells or rEPDR1 treatment led to re-duced lipid accumulation.Furthermore,the TG content significantly decreased compared with the model group(P<0.05).CONCLUSION:EPDR1 is expressed in various tissues of wild-type mice,but showed diminished expression in the liver tissues of diabetic mice.Nevertheless,enhancing the expression of EPDR1 can aid in reducing lipid accumula-tion in hepatocytes.These findings provide an experimental foundation for further exploration of the role of EPDR1 in the development of fatty liver in diabetic liver tissue.
8.Discussion on Li Dongyuan's Yin-Fire Theory and Its Modern Clinical Application
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(8):765-770
The Yin-Fire theory is the core content of Li Dongyuan's academic thought and has profound and extensive clinical guidance value.This paper analyzes the connotation and background of the Yin-Fire theory,and proposes that the core pathogenesis of Yin-Fire syndrome is qi deficiency without movement,and stagnation turning into fire;qi deficiency without rise,and dampness and turbidity flowing downward;qi deficiency without astringent,and Xiang-Fire rushing upward;qi deficiency and fire hyperactivity,which hurts body fluid and burns blood.This article summarizes the key points of diagnosis and treatment of various diseases by sorting out the commonly used prescriptions and medicines of Yin-Fire theory and its clinical application in miscellaneous internal medicine diseases,and deepens the understanding of the connotation of Yin-Fire syndrome.
9.Comparison between white light endoscopy and narrow-band imaging endoscopy in predicting histological healing of ulcerative colitis in remission
Tao HE ; Lingyu ZHU ; Peng PAN ; Lei LI ; Qiuye WANG ; Shilin QIU ; Liyan ZHANG ; Hui GAO ; Lianqiang SONG ; Shanming SUN
Chinese Journal of Digestive Endoscopy 2023;40(2):140-145
Objective:To investigate the predictive value of mucosal vascular pattern (MVP) under narrow-band imaging (NBI) enteroscopy in patients with ulcerative colitis (UC) in clinical remission for histological healing and clinical recurrence.Methods:A total of 142 patients with UC in clinical remission who visited the First Affiliated Hospital of Weifang Medical University from January 2018 to January 2021 were included in the study and underwent colonoscopy. The white light and NBI endoscopic images were collected and biopsies were obtained. The Mayo endoscopic score (MES) was calculated based on white light images, and MVP staging was evaluated based on mucosal vascular patterns under NBI. Nancy index (NI) was used to evaluate histological healing and patients were followed up for 1 year. The Spearman correlation coefficients of MES and MVP with histological healing and recurrence were calculated. The receiver operator characteristic (ROC) curve was plotted and the area under curve (AUC) was applied to evaluate the accuracy of white light and NBI endoscopy for predicting histological healing of UC in clinical remission.Results:According to the MVP criteria, 47 were defined as clear, 63 blurred, and 32 invisible. Spearman correlation analysis showed a significant correlation between MVP under NBI and histological healing ( r=0.549, P<0.001) and a moderate correlation between MES under white light and histological healing ( r=0.462, P<0.001). Spearman correlation analysis showed a moderate correlation between MVP under NBI and clinical recurrence ( r=0.451, P<0.001) and a moderate correlation between MES under white light and clinical recurrence ( r=0.352, P<0.001). AUC of NBI for diagnosing histological healing of UC in clinical remission was 0.809 (95% CI: 0.738-0.879), with a sensitivity of 84.6% (77/91) and specificity of 64.7% (33/51), superior to the white light endoscopy, of which AUC, sensitivity and specificity were 0.763 (95% CI: 0.678-0.848), 81.3% (74/91) and 66.7% (34/51). Conclusion:MVP staging under NBI could predict histological healing of UC patients in clinical remission and is superior to white light endoscopy.
10.Fetal right atrial isomerism diagnosed on prenatal ultrasound: a case report
Yanpeng SONG ; Haiyan YU ; Meiling ZHANG ; Lingyu SUN
Chinese Journal of Perinatal Medicine 2020;23(4):269-271
We reported a case of fetus with right atrial isomerism diagnosed by ultrasound prenatally. Right atrial isomerism was suspected based on several kinds of abnormalities detected at 24 gestational weeks by ultrasound imaging, such as levocardia complicated by complex cardiovascular malformations (double outlet of right ventricle, atrioventricular septal defect, pulmonary artery dysplasia, bilateral superior vena cava and infracardiac total anomalous pulmonary venous drainage), abnormal right-sided stomach bubble, midline liver, suspicious absence of the spleen, juxtaposition of the abdominal aorta and the inferior vena cava to the left side, and mirror-image right bronchia. Autopsy confirmed all of the prenatal diagnosis with an additional finding of splenic dysplasia. Right atrial isomerism should be considered when ultrasound findings indicate complex cardiovascular malformations. Given the high mortality rate of right atrium isomerism, prenatal diagnosis is of great importance.

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