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*
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Animals
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Hepatocytes/metabolism*
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Lipid Metabolism
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Mice
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Humans
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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AMP-Activated Protein Kinases/metabolism*
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Carnitine O-Palmitoyltransferase/metabolism*
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Diet, High-Fat
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Male
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Mice, Inbred C57BL
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Signal Transduction
2.Grey-scale Reversed T1-weighted MRI for Detecting Structural Lesions of the Sacroiliac Joint in Patients with Axial Spondyloarthritis
Ximeng LI ; Wenjuan LI ; Ke ZHANG ; Chaoran LIU ; Yunfei ZHU ; Yingying ZHAN ; Mingzhu LIANG ; Guobin HONG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(3):412-419
[Objective]To analyze the value of grey-scale reversed T1-weighted(rT1)MRI in the detection of structur-al lesions of the sacroiliac joint(SIJ)in patients with axial spondyloarthritis(ax-SpA).[Methods]Fifty-two ax-SpA pa-tients who underwent both MRI and CT in our hospital within a week from February 2020 to December 2022 were retrospec-tively included.Both sacral and iliac side of each SIJ on oblique coronal images were divided into anterior,middle and pos-terior portion.Two radiologists reviewed independently three groups of MRI including T1-weighted imaging(T1WI),rT1 and T1WI+rT1 images to evaluate the structural lesions like erosions,sclerosis and joint space changes in each of the 6 re-gions of the SIJ.One of the radiologist did the evaluation again one month later.CT images were scored for lesions by a third radiologist and served as the reference standard.Intra-class correlation coefficients(ICC)were calculated to test the inter-and intra-reader agreement for the assessment of SIJ lesions.A Friedman test was performed to compare the lesion results of MRI and CT image findings.We examined the diagnostic performance[accuracy,sensitivity(SE)and specifici-ty]of different groups of MRI in the detection of lesions by using diagnostic test.A McNemar test was used to compare the differences of three groups of MRI findings.[Results]CT showed erosions in 71 joints,sclerosis in 65 and joint space changes in 53.Good inter-and intra-reader agreements were found in three groups of MRI images for the assessment of le-sions,with the best agreement in T1WI+rT1.There were no difference between T1WI+rT1 and CT for the assessment of all lesions,nor between rT1 and CT for the assessment of erosions and joint space changes(P>0.05).T1WI+rT1 yielded better accuracy and SE than T1WI in detection of all lesions(Accuracy erosions:90.3%vs 76.9%;SE erosions:91.6%vs 76.1%;Accu-racy sclerosis:89.4%vs 80.8%;SE sclerosis:84.6%vs 73.9%;Accuracy joint space changes:86.5%vs 73.1%;SE joint space changes:84.9%vs 60.4%;P<0.05).rT1 yielded better accuracy and SE than T1WI in detection of erosions and joint space changes(Accuracy erosions:87.5%vs 76.9%;SE erosions:88.7%vs 76.1%;Accuracy joint space changes:85.6%vs 73.1%;SE joint space changes:83.0%vs 60.4%;P<0.05).[Conclusions]In the detection of SIJ structural lesions in ax-SpA,rT1 improves the diagnostic perfor-mance and T1WI+rT1 is more superior to others.
3.Correlation of digital breast tomosynthesis and pathological features with the outcome of breast-conserving surgery in early-stage breast cancer
Liu LIANGSHENG ; Ma WENJUAN ; Zhang YU ; Li YANBO ; Wang JIAHUI ; Lu HONG
Chinese Journal of Clinical Oncology 2024;51(12):611-615
Objective:To investigate the correlation between digital breast tomosynthesis(DBT)image features,pathological features,and the results of breast-conserving surgery(BCS)in early stage breast cancer.Methods:We retrospectively analyzed 422 cases of BCS resulting in successful breast preservation and 211 BCS cases that were followed by mastectomy.All of the patients underwent surgery at Tianjin Medical University Cancer Institute&Hospital between January 2019 and December 2023.Preoperative DBT images and clinicopathological features were assessed.A univariate Logistic regression analysis was performed to screen out the characteristics associated with BCS surgic-al results,after which multivariate Logistic regression analysis was performed to screen out the characteristics.Results:Univariate Logistic regression analysis showed that age(P=0.020),architectural distortion(P<0.001),breast composition(extremely dense,P=0.001),and mo-lecular subtype(Her2,P=0.001)were statistically different between the two groups.Multivariate Logistic regression analysis showed that ar-chitectural distortion(P<0.001),breast composition(extremely dense breast,P=0.003),and molecular subtype(Her2,P<0.001)differed signi-ficantly between the two groups.Conclusions:Breast composition,architectural distortion,and molecular subtype correlated with BCS res-ults.Extremely dense breast composition,architectural distortion,and Her2 subtype are associated with a higher possibility of conversion to mastectomy.These factors serve as effective predictive indicators of BCS results and thus aid clinicians in deciding the appropriate surgical strategies in the treatment of breast cancer.
4.Research on the deep learning model based on the combination of intratumoral and peritumoral dynamic contrast-enhanced MRI for predicting axillary lymph node metastasis in breast cancer
Yijun GUO ; Rui YIN ; Junqi HAN ; Zhaoxiang DOU ; Jingjing CHEN ; Peifang LIU ; Hong LU ; Wenjuan MA
Journal of Practical Radiology 2024;40(6):907-912
Objective To explore the value of deep learning models in predicting axillary lymph node(ALN)metastasis of breast cancer based on intratumoral and peritumoral dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI).Methods A retrospective analysis was conducted on cases from Tianjin Medical University Cancer Hospital and Laoshan Branch of Affiliated Hospital of Qingdao University,involving a total of 850 lesions in 850 patients.The region of interest within the tumor was delineated at the largest area of the lesion on the first enhancement images and automatically expanded by 3 mm and 6 mm in a conformal fashion.Deep learning prediction models based on ResNet50 were developed via intratumoral,peritumoral,and intratumoral combined peritumoral models,respectively,and a comprehensive prediction model was developed by integrating semantic features of imaging reports.Cases from Tianjin Medical University Cancer Hospital were randomly divided into training and test cohorts in a 7∶3 ratio,while cases from Laoshan Branch of Affiliated Hospital of Qingdao University served as the external validation cohort.The area under the curve(AUC),accuracy,sensitivity,specificity,F1-score,and Brier-score were calculated,respectively.Results The model incorporating intratumoral,peritumoral(3 mm),and semantic features demonstrated the highest performance,with AUC of 0.801[95%confidence interval(CI)0.765-0.845],0.781(95%CI 0.745-0.817),and 0.752(95%CI 0.700-0.793)in the training cohort,test cohort,and external validation cohort,respectively,and there was no significant difference in AUC between combined model and intratumoral/peritumoral model,respectively,but it demonstrated the higher sensitivity and F1-score,and the lower Brier-score.Conclusion Incorporating peritumoral images into the conventional model based on intratumoral images enhanced the predictive ability of ALN metastasis in breast cancer.
5.Effects of canagliflozin combined with amiloride or benzamil on bone metabolism in rats with nephrotic syndrome
Wei HUAN ; Xiao LI ; Wenjuan HONG ; Xiaofei LUO ; Xuefang WANG ; Qian LI ; Jiamao CHENG
Journal of Clinical Medicine in Practice 2024;28(2):78-83
Objective To investigate the effects of sodium-glucose cotransporter 2 inhibitor (SGLT2i)canagliflozin and epithelial sodium channel inhibitor amiloride or benzamil in combination on the bone metabolism in the rats with the nephrotic syndrome (NS) induced by doxorubicin. Methods In the 49 male SD rats selected, 7 were randomly selected as control group (NG), and 42 were built as adriamycin-induced nephropathy model by injecting adriamycin through the tail vein, and were randomly divided into model group (MG group), canagliflozin group (KG group), benzamil group (BH group), amiloride group (AL group), canagliflozin+benzamil group (KB group) and canagliflozin+amiloride group (KA group), with 7 cases in each group. Each medication group was given intragastric administration according to the body weight of rats regularly every day, NG group and MG group were given equal amount of normal saline, the course of treatment was 6 weeks. The 24-hour urinary protein (24 h-UTP) of each group was detected one day before treatment to verify the successful preparation of the model. At 6 weeks after treatment, the 24 h-UTP, urine sodium (UNa), urinary potassium (UK) levels in urine and the albumin (ALB), triglyceride (TG), cholesterol (TC), low density lipoprotein (LDL), serum calcium (SCa), sodium (SNa), potassium (SK), 25-hydroxyvitamin D (25-OH-D), alkaline phosphatase (ALP), parathyroid hormone (PTH), procollagen type Ⅰ N-terminal propeptide (PINP) and beta C-terminal cross-linked telopeptides of typeⅠ collagen (β-CTX) levels in serum were measured, respectively. Results After successful modeling, the levels of 24 h-UTP, TG, TC, LDL and SCa in the MG group were significantly increased, while the levels of ALB, 25-OH-D, ALP, PINP and PTH were significantly decreased (
6.Effects of Canagliflozin Combined with Amiloride and Benzamil in Rats with Doxorubicin-induced Nephrotic Syndrome
Wei HUAN ; Xiao LI ; Wenjuan HONG
Journal of Medical Research 2024;53(9):91-97
Objective To investigate the effects of canagliflozin combined with amiloride and benzamir on doxorubicin-induced ne-phrotic syndrome(NS)model rats.Methods A total of 49male SD rats were randomly divided into 7groups:normal control group(NG group),model group(MG group),canagliflozin group(KG group),benzamil group(BH group),amiloride group(AL group),cana-gliflozin+benzamil group(KB group)and canagliflozin+amiloride group(KA group),with 7 rats in each group.The NS model was established by injection of doxorubicin in the tail vein.The 24h-UTP of each group was detected one day before treatment to verify the successful preparation of the model.Each group was given intragastric administration according to the body weight of rats regularly every day,NG group and MG group were given equal amount of normal saline,the course of treatment was 6 weeks.After 6 weeks of treatment,the 24h-UTP,UNa,UK,UCl levels in urine and the albumin(ALB),triglyceride(TG),total cholesterol(TC),low density lipopro-tein(LDL),Urea,Crea,CysC,SNa,SK,SCl levels in serum were measured,respectively.The expression of serum transforming growth factor-β1(TGF-β1)and soluble thrombomodulin(sTM)were detected by enzyme-linked immunosorbent assay(ELISA).The expression of TGF-β1 gene was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The renal pathology of rats in each group were tested by the hematoxylin-eosin(HE)staining and Masson staining.Results After successful modeling,the levels of 24h-UTP,TG,TC,LDL in the MG group were increased,while the levels of ALB was decreased(P<0.05).After 6 weeks of drug intervention,compared with MG group,the levels of 24h-UTP,TC,TG,LDL were decreased,and the level of ALB was increased in all drug groups(P<0.05),and the level of TGF-β1 was decreased in the KG group(P<0.05),and the levels of CysC,UNa,TGF-β1,sTM was increased in the KA group(P<0.05).The results of HE staining and Masson staining showed that typical characteristics of focal segmental glomerulosclerosis appeared in the renal tissue of rats in MG group,all drug groups were observed in varying degrees of improvement.Conclusion Canagliflozin,benzamil,amiloride alone and canagliflozin combined with benzatrimil and amiloride could improve the macroproteinuria,hypoproteinemia and hyperlipidemia of doxorubicin-induced NS model rats.Canagli-flozin alone can effectively reduce TGF-β1 expression and thereby reduce kidney inflammation,but the combination of canagliflozin and amiloride may cause renal insufficiency and endothelial injury.
7.Physical health status and influencing factors of preschool children in Tibet
CHEN Ting, LIANG Meng, WANG Jiajuan, ZHAO Xin, CHENG Hong, DU Wenjuan, SUN Ruizhe
Chinese Journal of School Health 2023;44(11):1626-1630
Objective:
To explore physical health status and influencing factors of preschool children in Tibet, so as to provide a scientific reference and theoretical basis for the healthy development of physical fitness.
Methods:
Data were collected from children (3-6 years old) of Xizang national physical fitness monitoring, and a total of 1 521 preschool children were recruited who received questionnaire survey and physical fitness test. Independent sample t-test and one-way ANOVA were used to compare the differences in physical fitness indexes of preschool children in different groups. Chi square test and binary Logistic regression model were used to analyze the factors affecting physical health of preschool children.
Results:
The total qualified rate of physical fitness was 79.75%, among which the excellent rate was 3.16%, the good rate was 15.12%, the qualified rate was 61.47% and the unqualified was 20.25%. From the perspective of BMI, the excellent physical fitness rate (3.74%) and good physical fitness rate ( 17.47% ) were highest in healthy weight preschool children, and the qualified physical fitness rate of overweight preschool children (69.03%) was higher than that of obese (55.88%) and healthy weight preschool children (60.68%)( χ 2=53.56, P <0.01). From the perspective of ethnic, Tibetan children s physique proficiency (3.69%), good rate ( 17.13% ) than with the elevation of the Han nationality (0.74%, 5.88%), fraction defective (16.97%), lower than that of Han nationality (35.29%) ( χ 2=53.71, P <0.01); The results of chest circumference, skinfold thickness, body fat percentage, tennis throw distance, continuous jump of both feet, sitting forward bend and balance beam walking of Tibetan children were higher than those of Han children, and the results of quiet heart rate and standing long jump were lower than those of Han children ( t = 2.72 , 10.95, 9.66, 3.68, 3.88, 8.04, 3.56, 8.70, -4.39 , -4.40, P <0.01). Binary Logistic regression analysis showed that Tibetans ( OR =2.29), breastfeeding ( OR =1.51), body dynamics outdoor daily exercise duration 30-90 min (30-<60 min ;OR = 2.03 ; 60-90 min: OR =2.22) were positively correlated with physical health of preschool children ( P <0.05).
Conclusions
The total physical qualification rate of preschool children aged 3-6 years old in Tibet is lower than the national average. Ethnic group, feeding pattern during infancy, and physical activity are all factors that affected the physical fitness of preschool children in Tibet. It is of great significance to improve the physique of preschool children in Tibet to promote their sustainable and healthy development.
8.Exploration and thinking of online teaching of medical microbiology experiment
Mei QI ; Hong WANG ; Yabin ZHOU ; Juan LIU ; Wei TANG ; Yizhe CHENG ; Yundong SUN ; Wenjuan LI ; Shili LIU ; Weifang ZHANG
Chinese Journal of Medical Education Research 2023;22(4):528-531
Medical microbiology experiment is faced with many problems in online teaching. This study adopts the teaching mode of online live broadcast + operation video + virtual experiment, and make up the operation gap to some extent through operation video and virtual experiment. The mode of assessment is subjective thinking question (closely following the operation process) + experiment design + literature review (focusing on the key technology or new technology of clinical assessment that cannot be carried out due to the limitation of conditions in traditional experiments, such as mass spectrometry, fluorescence quantitative PCR, and G-test), and it is helpful to understand students' mastery of teaching objectives, and the ability of comprehensive application and innovative thinking. The student questionnaire shows that most students hold a positive attitude towards the online experimental teaching mode, and the quality of students' homework shows that most students have a good learning effect.
9.Relationship of common dyadic coping to marital satisfaction and quality of life for patients with brain injury and their spouses in a rehabilitation facility: using common fate model
Wenjuan FU ; Jianhua HOU ; Xiaonan YU ; Tianyong CHEN
Chinese Journal of Rehabilitation Theory and Practice 2023;29(12):1446-1453
ObjectiveTo investigate common dyadic coping (CDC) in linking with marital satisfaction and quality of life (QOL) in patients with brain injury and their spouses in a rehabilitation facility by using common fate model (CFM). MethodsFrom October, 2022 to June, 2023, 101 brain injury inpatients and their spouses in Beijing Bo'ai Hospital completed the questionnaire of Dyadic Coping Inventory, Kansas Marital Satisfaction Scale and World Health Organization Quality of Life. ResultsThe level of CDC between patients and their spouses significantly positively correlated with their marital satisfaction for both partners (β = 0.814, P < 0.001), as well as correlated with their quality of life (β = 0.271, P = 0.038; β = 0.481, P < 0.001). For the dimensions of QOL, the physical, psychological, social relationship and environmental dimensions significantly positive correlated with the CDC for the spouses, and only psychological and social relationship dimensions for the patients. ConclusionFacing the stress of brain injury, the level of CDC within couples can positively predict their marital satisfaction and QOL, and effect seems stronger for the spouses. It is advisable to consider both brain injured patients and their spouses as a whole to promote psychological adaptation and improve rehabilitation outcomes.
10.Clinical characteristics of 174 neonates with SARS-CoV-2 infection
Limei ZHANG ; Ling LIU ; Xing ZHOU ; Wenjuan XI ; Hong HUANG
Chinese Journal of Neonatology 2023;38(11):651-654
Objective:To study the clinical characteristics of SARS-CoV-2 infection in neonates.Methods:From December 2022 to January 2023, neonates with PCR confirmed SARS-CoV-2 infection admitted to the Department of Neonatology of our hospital were retrospectively studied.The clinical data including epidemiological history, clinical manifestations, laboratory results, treatment and prognosis were analyzed.Results:A total of 174 neonates were enrolled, including 152(87.4%) with clear exposure to SARS-CoV-2 patients prior to onset. 73 cases (42.0%) were mild type, 72(41.4%) were moderate type, 26(14.9%) were severe type and 3(1.7%) were critically severe type. 109 cases had fever, 118 had respiratory symptoms including cough, nasal congestion and spitting up bubbles, 56 had gastrointestinal symptoms including decreased appetite, vomiting, and diarrhea and 35 had neurological symptoms including drowsiness, poor response and irritability. All 174 patients had positive nucleic acid test. White blood cell (WBC) was normal in 151 cases, decreased in 14 and increased in 9. 8 cases showed elevated C-reactive protein(CRP). Lactate dehydrogenase (LDH) was increased in 74 cases, creatine kinase (CK) increased in 22 cases and alanine aminotransferase (ALT) increased in 3 cases. Chest X-ray or CT scan showed 102 cases with pneumonia. 26 cases required nasal cannula oxygen therapy and 4 cases required respiratory support (3 invasive and 1 non-invasive). 173 cases were discharged fully recovered and 1 died after withdrawal of treatment for total anomalous pulmonary venous drainage (TAPVD) .Conclusions:Neonates are susceptible to SARS-CoV-2.Most patients have a history of exposure prior to disease onset. 83.3% of all cases are mild and moderate types.Respiratory symptoms are common. Symptomatic treatments are effective with an overall good prognosis.


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