1.Acetyl-coenzyme A synthetase 2-mediated acetyl-coenzyme A accumulation promotes mitophagy and tumor growth via increased H3K27ac in hepatitis B virus-related hepatocellular carcinoma
Shan LI ; Jie HU ; Yihan YAN ; Xinrui LIU ; Xiao DONG ; Huijun LIANG ; Xin TANG ; Junji TAO ; Rong ZHANG ; Yuan HU ; Ailong HUANG ; Kai WANG ; Ni TANG
Clinical and Molecular Hepatology 2026;32(2):661-682
Background/Aims:
Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial.
Methods:
A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining.
Results:
Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth.
Conclusions
These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.
2.Principle and application of photon counting detectors
Xinrui ZHANG ; Shumin CHEN ; Yizhong WANG ; Junru REN ; Ailong CAI ; Lei LI ; Bin YAN
China Medical Equipment 2024;21(2):179-183
Photon Counting Detector(PCD)is a device used to detect X-ray photons,which can directly convert the energy of photons into electrical signals to achieve photon counting and measurement.PCD-based energy spectrum computed tomography(PCD-CT)technology can provide additional energy spectral imaging information,and improve imaging quality while reducing radiation dose.Compared with energy integrating detectors(EID),PCD has advantages of high energy conversion efficiency,good imaging quality,exquisite structural design,and wide application range.It has broad application prospects in ultra-low-dose CT,specific disease diagnosis,and industrial inspection.The application of PCD-CT in spectral CT imaging was reviewed to provide a useful reference for its application in clinical medical diagnosis and industrial applications.
3.Comparative study and enlightenment on the evaluation system of domestic and foreign universities under the background of "Double First-Class"
Hong ZHANG ; Ailong HUANG ; Yanbin HOU
Chinese Journal of Medical Education Research 2021;20(5):497-501
The construction of "Double First-class" has started a new journey of higher education in China. Scientific, reasonable and objective evaluation on universities is the foundation and important guarantee for the construction of first-class universities. On the basis of introducing the main university evaluation system at home and abroad, the selection of representative Chinese and world university evaluation system for comparative study has strong guiding significance for the establishment of first-class university evaluation system. Under the background of "Double First-Class" construction, based on Chinese characteristics, the author puts forward some thoughts and suggestions on perfecting the university evaluation system in China.
4.Study on HIV prevention related knowledge-motivation-psychological model in men who have sex with men, based on a structural equation model
Yuan JIANG ; Yalan DOU ; Aijie CAI ; Zhao ZHANG ; Tian TIAN ; Jianghong DAI ; Ailong HUANG
Chinese Journal of Epidemiology 2016;37(2):281-285
Objective Knowledge-motivation-psychological model was set up and tested through structural equation model to provide evidence on HIV prevention related strategy in Men who have Sex with Men (MSM).Methods Snowball sampling method was used to recruit a total of 550 MSM volunteers from two MSM Non-Governmental Organizations in Urumqi,Xinjiang province.HIV prevention related information on MSM was collected through a questionnaire survey.A total of 477 volunteers showed with complete information.HIV prevention related Knowledge-motivationpsychological model was built under related experience and literature.Relations between knowledge,motivation and psychological was studied,using a ‘structural equation model’ with data from the fitting questionnaires and modification of the model.Results Structural equation model presented good fitting results.After revising the fitting index:RMSEA was 0.035,NFI was 0.965 and RFI was 0.920.Thereafter the exogenous latent variables would include knowledge,motivation and psychological effects.The endogenous latent variable appeared as prevention related behaviors.The standardized total effects of motivation,knowledge,psychological on prevention behavior were 0.44,0.41 and 0.17 respectively.Correlation coefficient of motivation and psychological effects was 0.16.Correlation coefficient on knowledge and psychological effects was-0.17 (P<0.05).Correlation coefficient of knowledge and motivation did not show statistical significance.Conclusion Knowledge of HIV and motivation of HIV prevention did not show any accordance in MSM population.It was necessary to increase the awareness and to improve the motivation of HIV prevention in MSM population.
5.Protective effects of schisandrin B on hypoxia injury of HK-2 cells
Ailong LU ; Xiaoyue TAN ; Mianzhi ZHANG ; Yinna WU
Tianjin Medical Journal 2015;43(5):465-469
Objective To explore the protective effects of schisandrin B (Sch B) on hypoxia injury induced by cobaltous chloride (CoCl2) in human proximal renal tubular epithelial (HK-2) cells, and the possible mechanism thereof. Methods HK-2 cells were randomly assigned to four groups:control group (Con, cells were untreated), CoCl2 group (CoCl2, cells were treated with 600μmol/L CoCl2 for 24 h), Sch B pretreat group (CoCl2+Sch B, cells were pretreated with 1μmol/L and 10μmol/L Sch B for 2 h) and Sch B group (Sch B, cells were treated with 1μmol/L and 10μmol/L Sch B for 2 h). CCK-8 kit was used to detect the cell viability of four groups. Flow cytometry was used to detect the apoptotic rate of four groups. The protein expression of hypoxia-inducible factor 1α(HIF-1α) was assessed by Western blot assay. The expressions of HIF-1α and inducible nitric oxide synthase (iNOS) mRNA were determined by RT-PCR. Results Compared with the control group, after treated with 600 μmol/L CoCl2, the cell viability was decreased, and the apoptosis was increased, the expressions of HIF-1α and iNOS mRNA were up-regulated in HK-2 cells. There was no significant difference in the expression of HIF-1α mRNA between control group and CoCl2 group. Compared with the CoCl2 group, after pretreated with 1μmol/L and 10μmol/L Sch B, the cell viability was increased and the apoptosis was decreased, the expressions of HIF-1α and iNOS were down-regulated in HK-2 cells. There were no significant differences in the cell viability and apoptotic rate between control group and Sch B group. Conclusion Pretreatment with Sch B can reduce the apoptosis of HK-2 cells by inhibiting the expression of HIF-1α and iNOS mRNA, which shows protective effects on hypoxia injury.
6.Establishment of an HBV chronic hepatitis B infection mouse model by vivo transduction of HBV cccDNA.
Tingting ZHAO ; Xiaosong LI ; Wenwei YIN ; Xuefei CAI ; Wenlu ZHANG ; Feilan CHEN ; Guoqi LAI ; Ailong HUANG
Chinese Journal of Hepatology 2014;22(4):260-265
OBJECTIVETo generate a mouse model of chronic hepatitis B (CHB) infection by performing in vivo transduction of hepatitis B virus (HBV) covalently closed circular (ccc)DNA.
METHODSNude mice were injected with HBV cccDNA at doses of 1.5, 1.0 or 0.5 mug/ml. A control group was generated by giving equal injection volumes of physiological saline. The serum levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) on post-injection days 1 and 3, weeks 1-6, 8 and 10 were assayed by reflection immunoassay. At post-injection week 10, all animals were sacrificed and liver tissues were collected. Copies of HBV DNA in serum and liver tissue were detected by real-time PCR. HBV antigens in liver tissue were detected of by immunohistochemistry. Pathological analysis of liver tissue carried out with hematoxylin-eosin staining. Linear correlation of data was determined by statistical analysis.
RESULTSHBsAg and HBeAg were detected in sera from all three groups of cccDNA-injected mice staring at post-injection day 1 and lasting through week 10. The levels of HBsAg over the 10-week period showed two patterns of increase-decrease;the lowest level was detected at week 4 and the highest level was detected at week 8. In contrast, the levels of HBeAg over the 10-week period showed three patterns of increase-decrease; the lower levels were detected at weeks 2 and 4 and the higher levels at weeks 3 and 6. HBV DNA copies in liver tissues showed a cccDNA dose-dependent descending trend over the 10-week study period (1.5 mug/ml:1.14E+07 ± 6.51E+06 copies/g, 1.0 mug/ml:9.81E+06 ± 9.32E+06 copies/g, and 0.5 mug/ml:3.72E+06 ± 2.35E+06 copies/g; Pearson's r =0.979). HBV DNA copies in sera showed the pattern of 1.0 mug/ml cccDNA more than 1.5 mug/ml cccDNA more than 0.5 mug/ml cccDNA, and in general were higher than those detected in the liver tissues. Liver tissues from all cccDNA-injected mice showed positive immunohistochemistry staining for both HBsAg and HBeAg. HE staining showed that the liver tissues of all cccDNA-injected mice had severe fatty and vacuolar degeneration and less obvious structure of liver lobules (compared to the liver tissues from control mice).
CONCLUSIONThe CHB mouse model successfully established in this study by in vivo transduction of HBV cccDNA may represent a useful tool to study the pathogenic mechanisms and potential antiviral treatments of human CHB.
Animals ; DNA, Circular ; administration & dosage ; DNA, Viral ; administration & dosage ; Disease Models, Animal ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; physiology ; Hepatitis B, Chronic ; virology ; Male ; Mice ; Mice, Nude ; Transduction, Genetic ; Virus Replication
7.Galectin-3 in differential diagnosis between benign and malignant thyroid follicular tumor
Donghang HUANG ; Zhenhui YOU ; Huashui LI ; Ailong ZHANG ; Hang WANG ; Lizhen QIU ; Qiang LIN
Journal of Endocrine Surgery 2013;7(5):424-425
Objective To analyze the expression of Galectin-3 in thyroid follicular tumors and its clinical significance in differential diagnosis between benign and malignant thyroid follicular tumor.Methods The expression of Galectin-3 in 120 cases of thyroid follicular carcinoma and 80 cases of thyroid follicular adenoma was detected by immunohistochemical technique.Results The expression rate of Galectin-3 in thyroid follicular carcinoma was significantly higher than that in follicular adenoma(84% vs 19%,P < 0.01).Strong positive expression of Galectin-3 was found in 40% cases of thyroid follicular carcinoma and no case of thyroid follicular adenoma.Conclusions The expression of Galectin-3 can be regarded as an important parameter for differential diagnosis between benign and malignant thyroid follicular tumor.
8.Clinicopathologic characteristics and treatment of medullary thyroid carcinoma
Donghang HUANG ; Huashui LI ; Ailong ZHANG ; Hang WANG ; Lizhen QIU ; Qiang LIN ; Zhenhui YOU
Journal of Endocrine Surgery 2013;7(4):275-277
Objective To explore the clinicopathologic characteristics and treatment of medullary thyroid carcinoma(MTC).Methods The data of 42 cases of MTC admitted to Fujian Medical University Provincial Clinical College from Jan 1995 to Feb 2010 were retrospectively analyzed.Surgery was performed in all the 42 cases.All were proved to be MTC by pathology.Results Surgery was performed in all the 42 cases.All were proved to be MTC by pathology.The lymph node metastasis rate was 76.19% (32/42).The central lymph node metastasis rate was 61.90% (26/42).All the 42 cases were followed up for 1 to 502 months with 102 months as the median.35 cases(83.33%)were followed up for more than 5 years and the 5-year overall survival rate was 85.71% (30/35).Death occurred in 5 cases.Conclusions The lymph node metastasis rate of MTC is high.The treatment should be based on the principle of radical resection.Total thyroidectomy should be recommended to treat primary tumor.Lymph node dissection should be as thorough as possible.Central compartment neck dissection should be done in all cases.
9.The diagnosis and treatment strategy of pancreatic injury
Donghang HUANG ; Qiang LIN ; Zhenhui YOU ; Muzhen HE ; Ailong ZHANG ; Huashui LI ; Hang WANG ; Lizhen QIU ; Ruijuan WANG
Journal of Endocrine Surgery 2012;6(6):394-396
Objective To summarize the experience of diagnosis and treatment strategy of pancreatic injury.Methods The data of 36 cases of pancreatic injurics admitted to Fujian Medical University Provincial Clinical College from 1990 to 2011 were analyzed retrospectively.Results 14 cases(39%)were diagnosed preoperatively,and the other cases were diagnosed during the laparotomy.2 cases underwent non-surgical treatment.34 cases underwent surgical treatment,among whom 23 cases underwent pancreatic debridement and drainage,6 cases underwent distal pancreatectomy(4 cases undergoing distal pancreatectomy plus splenectomy included),4 cases underwent distal Roux-Y pancreajejunostomy plus proximal pancreas closure,and 1 case underwent pancreatoduodenectomy.31 cases (86%) were cured,and 5 cases died (14%).Conclusions Most of the pancreatic injury is diagnosed through laparotomy.Surgical opcration is the main approach to treat pancreatic injury.Nonsurgical treatment is primarily limited to grade Ⅰ and Ⅱ pancreatic injury without obvious peritonitis,major pancreatic duct injury,and associated injuries.Surgical procedure should be selected based on the grading scale of pancreatic injury,associated injuries and overall conditions of the patient.
10.Comparison of real-time genotyping and quantitative PCR,multiplex-PCR and sequence analysis for hepatitis B virus genotypes B and C
Xiuyu ZHANG ; Yao ZHAO ; Wenlu ZHANG ; Yuan HU ; Zuowei YUAN ; Ailong HUANG
Chinese Journal of Microbiology and Immunology 2010;30(12):1154-1158
Objective To evaluate the real-time genotyping and quantitative PCR(RT-GQ-PCR)method by comparing it with direct sequence analysis and the multiplex-PCR method.Methods RT-GQ-PCR,direct sequence analysis and the multiplex-PCR method were used to detect HBV genotypes of 113 patient samples with HBV-DNA positive.ResultsThe detection rate of RT-GQ-PCR and direct sequence analysis was 100%,and the multiplex-PCR is 94.69%.The concordance between RT-GQ-PCR and the multiplex-PCR is perfect(Kappa value =0.915),and the consistency of RT-GQ-PCR and direct sequence analysis is pretty good(Kappa value = 0.742),specially at detecting single genotype.Twenty-eight samples with genotypes B and C dual infections were detected by RT-GQ-PCR,but only 19 samples by the multiplexPCR and 13 samples by direct sequence analysis.Conclusion The RT-GQ-PCR is convenient,rapid and accurate in HBV genotyping,especially more sensitive than direct sequence analysis and the multiplex-PCR for detecting dual genotypes.The method is applicable for large-scale epidemiological study.

Result Analysis
Print
Save
E-mail