1.Long-chain acylcarnitine deficiency promotes hepatocarcinogenesis.
Kaifeng WANG ; Zhixian LAN ; Heqi ZHOU ; Rong FAN ; Huiyi CHEN ; Hongyan LIANG ; Qiuhong YOU ; Xieer LIANG ; Ge ZENG ; Rui DENG ; Yu LAN ; Sheng SHEN ; Peng CHEN ; Jinlin HOU ; Pengcheng BU ; Jian SUN
Acta Pharmaceutica Sinica B 2025;15(3):1383-1396
Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.
2.Transient Peripheral Carotid Inflammation Syndrome Diagnosed by Contrast-enhanced Ultrasound:A Case Report
Chunlei PAN ; Ying WANG ; Yahong WANG ; Li ZHANG ; Zhitong GE ; Yu CHEN ; Sheng CAI ; Hongyan WANG ; Xiao YANG ; Jianchu LI
Medical Journal of Peking Union Medical College Hospital 2025;16(3):785-789
Transient perivascular inflammation of the carotid artery(TIPIC)syndrome is a relatively rare disease,and ultrasound is the first screening method for initial diagnosis of the disease.Contrast-enhanced ultrasound(CEUS)has unique advantages in the follow-up of patients with TIPIC syndrome.This paper reports a patient with TIPIC syndrome who was treated with acute left neck pain.The inflammation was significantly re-lieved and subsided after treatment with non-steroidal anti-inflammatory drugs.The ultrasound changes of carotid artery lesions in this patient during follow-up were analyzed,and the application value of CEUS in the follow-up diagnosis of this disease was summarized,in the hope of providing clinical reference.
3.Mechanism of nodakenin in relieving neuropathic pain
Hongyan LIU ; Yachen LI ; Gege SHENG ; Haili ZHU ; Jiliang WU
Tianjin Medical Journal 2025;53(1):35-41
Objective To investigate the effect and mechanism of nodakenin(Nod)in neuropathic pain(NP).Methods Differential expression genes in the primary somatsensory cortex(S1)of NP data and overlapping genes between the dataset and mitochondrial data were screened and analyzed.Overlapping gene interaction networks were overlapped and core genes were screened.A total of 27 mice were randomly divided into the sham operation group,the model group and the drug administration group(9 mice/group).The chronic compression injury model of sciatic nerve was constructed in the model group and the drug administration group.Nod 10 mg/kg was intraperitoneally injected into the drug administration group for 1 week.Changes of pain behavior and motor ability in mice were detected.HE staining and Nissl staining were used to detect effects of nerve injury and inflammation on brain tissue of S1 region of mice.The expression levels of interleukin-1β,early gene(c-Fos),panthenol-cytochrome c reductase complex III subunit(Uqcrq)and ubiquinone oxidoreductase subunit(Nduf)b5 in S1 brain region were analyzed by Western blot assay.Molecular docking was used to study the target of Nod.PC12 cells were divided into the control group,the IL-1β group(1 μmol/L IL-1β treatment)and the IL-1β+Nod group(1 μmol/L IL-1β+1 μmol/L Nod treatment),and mitochondrial membrane potential was detected in each group.Results In the NP dataset GSE180627,S1 brain region contained 293 differentially expressed genes,and the mitochondrial data contained 1 082 genes.There were 34 overlapping genes,and genes related to oxidative phosphorylation and electron transport chain were enriched.The protein interaction network showed that core genes included electron transport chain related proteins Ndufb5,Uqcrq,Ndufs8,Ndufa7,Ndufa3,Cox6b1 and Mrps33.Compared with the model group,the mechanical foot shrinkage threshold,thermal foot shrinkage reflex latency and rod rotation residence time of mice were increased in the drug administration group,the number of inflammatory infiltrating cells in S1 tissue and the number of Nislet bodies in neurons,expression levels of c-Fos and IL-1β in neurons were decreased,and expression levels of Uqcrq and Ndufb5 were increased(P<0.05).Molecular docking showed that Nod could bind Uqcrq and Ndufb5.Compared with the IL-1β group,the fluorescence signal of mitochondrial membrane potential was enhanced in the IL-1β+Nod group(P<0.05).Conclusion Nodakenin can improve pain behavior in mice,and its mechanism involves ameliorating mitochondrial damage in S1.
4.Mechanism of nodakenin in relieving neuropathic pain
Hongyan LIU ; Yachen LI ; Gege SHENG ; Haili ZHU ; Jiliang WU
Tianjin Medical Journal 2025;53(1):35-41
Objective To investigate the effect and mechanism of nodakenin(Nod)in neuropathic pain(NP).Methods Differential expression genes in the primary somatsensory cortex(S1)of NP data and overlapping genes between the dataset and mitochondrial data were screened and analyzed.Overlapping gene interaction networks were overlapped and core genes were screened.A total of 27 mice were randomly divided into the sham operation group,the model group and the drug administration group(9 mice/group).The chronic compression injury model of sciatic nerve was constructed in the model group and the drug administration group.Nod 10 mg/kg was intraperitoneally injected into the drug administration group for 1 week.Changes of pain behavior and motor ability in mice were detected.HE staining and Nissl staining were used to detect effects of nerve injury and inflammation on brain tissue of S1 region of mice.The expression levels of interleukin-1β,early gene(c-Fos),panthenol-cytochrome c reductase complex III subunit(Uqcrq)and ubiquinone oxidoreductase subunit(Nduf)b5 in S1 brain region were analyzed by Western blot assay.Molecular docking was used to study the target of Nod.PC12 cells were divided into the control group,the IL-1β group(1 μmol/L IL-1β treatment)and the IL-1β+Nod group(1 μmol/L IL-1β+1 μmol/L Nod treatment),and mitochondrial membrane potential was detected in each group.Results In the NP dataset GSE180627,S1 brain region contained 293 differentially expressed genes,and the mitochondrial data contained 1 082 genes.There were 34 overlapping genes,and genes related to oxidative phosphorylation and electron transport chain were enriched.The protein interaction network showed that core genes included electron transport chain related proteins Ndufb5,Uqcrq,Ndufs8,Ndufa7,Ndufa3,Cox6b1 and Mrps33.Compared with the model group,the mechanical foot shrinkage threshold,thermal foot shrinkage reflex latency and rod rotation residence time of mice were increased in the drug administration group,the number of inflammatory infiltrating cells in S1 tissue and the number of Nislet bodies in neurons,expression levels of c-Fos and IL-1β in neurons were decreased,and expression levels of Uqcrq and Ndufb5 were increased(P<0.05).Molecular docking showed that Nod could bind Uqcrq and Ndufb5.Compared with the IL-1β group,the fluorescence signal of mitochondrial membrane potential was enhanced in the IL-1β+Nod group(P<0.05).Conclusion Nodakenin can improve pain behavior in mice,and its mechanism involves ameliorating mitochondrial damage in S1.
5.Meta analysis of OCTA for detecting blood vessel density changes after open-angle glaucoma surgery
Yu ZHAO ; Rong BAI ; Hongyan HAO ; Weibo CHEN ; Sheng LI ; Xiao CAO ; Chen TIAN ; Jun LI
Chongqing Medicine 2024;53(18):2838-2846
Objective To systematically evaluate the value of optical coherence tomography angiogra-phy (OCTA) for detecting the vessel density (VD) changes after open-angle glaucoma (OAG) surgery.Meth-ods The studies on OCTA for detecting the VD changes after OAG surgery were searched in the CNKI,WanFang,VIP,SinoMed,PubMed,Embase and Web of Science databases from the database establishment to May 2024.Literature screening,data extraction and risk of bias assessment of included studies were conducted independently by two reviewers.Descriptive analysis was adopoted for the systematic evaluation,the meta a-nalysis was conducted by using the R software and mean difference (MD) and its 95%CI were calculated.Re-sults A total of 13 studies were included,involving 472 patients with 500 tested eyes.The results of meta-a-nalysis showed that compared with pre-surgery,VD around the optic nerve head (ONH) and in nasal superi-or,temporal inferior,temporal superior,superior temporal and superior nasal regions at postoperative 6 months were significantly decreased.VD in the perimacular,perimacular superior hemisphere,permacular su-perior hemisphere,perimacular superior and permacular superior regions at postoperative 6 months were sig-nificantly increased.Conclusion OCTA could effectively detect the postoperative VD changes in the patients with OAG and predict postoperative visual function changes in glaucoma,and could serve as an effective test means for assessing the clinical treatment effect of the patients with OAG.
6.Transient Peripheral Carotid Inflammation Syndrome Diagnosed by Contrast-enhanced Ultrasound: A Case Report
Chunlei PAN ; Ying WANG ; Yahong WANG ; Li ZHANG ; Zhitong GE ; Yu CHEN ; Sheng CAI ; Hongyan WANG ; Xiao YANG ; Jianchu LI
Medical Journal of Peking Union Medical College Hospital 2024;16(3):785-789
Transient perivascular inflammation of the carotid artery (TIPIC) syndrome is a relatively rare disease, and ultrasound is the first screening method for initial diagnosis of the disease. Contrast-enhanced ultrasound (CEUS) has unique advantages in the follow-up of patients with TIPIC syndrome. This paper reports a patient with TIPIC syndrome who was treated with acute left neck pain. The inflammation was significantly relieved and subsided after treatment with non-steroidal anti-inflammatory drugs. The ultrasound changes of carotid artery lesions in this patient during follow-up were analyzed, and the application value of CEUS in the follow-up diagnosis of this disease was summarized, in the hope of providing clinical reference.
7.Effect of feeding training based on solution-focused brief therapy on swallowing function in stroke patients with dysphagia
Yingji QIAN ; Caili REN ; Hongyan CHENG ; Li YOU ; Hongqun FANG ; Lu WANG ; Jia SHENG
Journal of Navy Medicine 2024;45(12):1255-1260
Objective To explore the effect of feeding training based on solution-focused brief therapy on swallowing function in stroke patients with dysphagia.Methods Patients with dysphagia after stroke who were hospitalized in Wuxi Central Rehabilitation Hospital from January 2021 to February 2022 were selected in this study.They were divided into control group and observation group according to the time of admission,with 55 patients in each group.The control group received routine nursing.The observation group received routine nursing and feeding training based on solution-focused brief therapy.The negative emotions,swallowing function and quality of life of patients were evaluated before and after nursing intervention.Results There was no significant difference in the scores of anxiety,depression,water drinking test,or swallowing scale between the two groups before nursing intervention(P>0.05).The scores of anxiety,depression,and water drinking test in the observation group were significantly lower than those in the control group after nursing intervention(P<0.05),and the scores of the quality of life in the observation group were significantly higher than those in the control group(P<0.05).Conclusion Feeding training based on the solution-focused brief therapy can alleviate anxiety and depression,and improve swallowing function,the recovery and the quality of life for stroke patients with dysphagia.
8.Advances in new antivirals for chronic hepatitis B.
Yanhua TANG ; Hongyan LIANG ; Ge ZENG ; Sheng SHEN ; Jian SUN
Chinese Medical Journal 2022;135(5):571-583
Chronic hepatitis B virus (HBV) infection remains a global health burden. Timely and effective antiviral therapy is beneficial for patients with HBV infection. With existing antiviral drugs, including nucleos(t)ide analogs and interferon-alfa, patients can achieve viral suppression with improved prognosis. However, the rate of hepatitis B surface antigen loss is low. To achieve a functional cure and even complete cure in chronic hepatitis B patients, new antivirals need to be developed. In this review, we summarized the advantages and disadvantages of existing antiviral drugs and focused on new antivirals including direct-acting antiviral drugs and immunotherapeutic approaches.
Antiviral Agents/therapeutic use*
;
Hepatitis B/drug therapy*
;
Hepatitis B Surface Antigens
;
Hepatitis B virus
;
Hepatitis B, Chronic/drug therapy*
;
Hepatitis C, Chronic/drug therapy*
;
Humans
9.The prevalence and risk factors of diabetic peripheral artery disease in Chinese communities
Li QIN ; Bo CHEN ; Jingya NIU ; Jun WANG ; Zhanguo WANG ; Ming WU ; Jinyi ZHOU ; Qingjun ZHANG ; Fang ZHOU ; Zhengyuan ZHOU ; Ning ZHANG ; Hongyan LYU ; Hongyan SHENG ; Wenjuan WANG
Chinese Journal of Epidemiology 2022;43(12):1932-1938
Objective:To investigate the prevalence and risk factors of diabetic peripheral artery disease (PAD) in patients with type 2 diabetes mellitus (T2DM) managed in primary health care in China.Methods:A total of 2 528 T2DM patients were selected using a two-stage cluster random sampling method based on the baseline survey of the "China Diabetic Foot Prevention Model Project." The study was conducted in 2015 among T2DM patients in 8 primary healthcare centers in Changshu county and Jiang'an district of Wuhan, China. Data collection methods included a questionnaire, body measurement, and blood glucose detection. The Ankle-Brachial Index (ABI) is the most widely used noninvasive vascular test. A binary logistic regression model was used to analyze the influence factors.Results:The prevalence of PAD was 11.2% among the diabetic patients managed in primary health care in the two cities. The prevalence of PAD under 55 years old, 55- years old, 65- years old, and ≥75 years old were 7.8%, 6.0%, 12.9% and 22.5%, respectively. Multivariate stepwise logistic regression identified influence factors included older age, higher education level, smoking, drinking, postprandial glucose uncontrol, and prior myocardial infarction or angina. Compared to age <55 years, the odds ratio for PAD were 0.74 for 55- years (95% CI: 0.43-1.28), 1.72 for 65- years (95% CI: 1.05-2.81), 3.56 for 75 years and above (95% CI: 2.07-6.11), respectively. Compared to patients with education in primary school and below, the odds ratio was 1.37 (95% CI: 0.97-1.94), 2.48 (95% CI: 1.73-3.55), 1.99 (95% CI: 1.26-3.13) for those with education levels of junior high school, senior high school, and college, respectively. Current smoking ( OR=1.49, 95% CI: 1.02-2.17), current drinking ( OR=0.45, 95% CI: 0.28-0.71), postprandial glucose uncontrol (2 h postprandial plasma glucose >10.0 mmol/L: OR=1.72, 95% CI: 1.22-2.43), and prior myocardial infarction or angina ( OR=2.32, 95% CI: 1.50-3.61) were influencing factors of PAD. Conclusions:Despite the high prevalence of PAD in diabetes managed in primary health care; multiple risk factors are not effectively aware of and under control. It is urgent to promote ABI screening and standardized management for diabetes, especially in primary health care.
10.Effects of CYP2C9*3 Gene Polymorphism on Therapeutic Efficacy of Benzbromarone in Lowering Uric Acid and Its Hepatotoxicity
Bi SHENG ; Junhua MENG ; Jing AN ; Jinhu WU ; Hongyan SONG ; Jiangjian LI ; Ling CHEN
China Pharmacy 2021;32(6):725-728
OBJECTIVE:To study the effects o f CYP2C9*3 gene polymorphism on therapeutic efficacy of benzbromarone in lowering uric acid and its hepatotoxicity. METHODS :A retrospective study was conducted to analyze the relevant clinical indicators and genotypes of 196 gout patients who received benzbromarone and CYP2C9*3 gene polymorphism test in Wuhan third hospital from Jan. 2018 to Sept. 2019. RESULTS :Among 196 patients,179,15 and 2 patients with CYP2C9*3 genotypes * 1/*1, *1/*3 and * 3/*3 genotypes were found ,respectively,and the distribution of each genotype was in line with Hardy-Weinberg balance(P>0.05). Before treatment ,there were no significant differences in the levels of UA ,Scr,ALT,AST and CRP between *1/*1 genotype and * 1/*3+*3/*3 genotype(P>0.05). After 4 weeks of treatment ,the UA ,Scr,CRP levels of patients with * 1/*1 genotype as well as the UA and CRP levels of patients with * 1/*3+*3/*3 genotype were significantly reduced ,the UA level of patients with * 1/*1 genotype was significantly lower than that of patients with * 1/*3+*3/*3 genotype(P<0.05 or P<0.01). The ALT and AST levels had no obvious changes in patients with different genotype before and after treatment ,and they were in the normal range. No serious abnormal liver function was observed during the treatment. CONCLUSIONS :Therapeutic efficacy of benzbromarone in lowering uric acid in gout patients with CYP2C9*3 genotypes * 1/*1 genotype is better than that of * 1/*3 and * 3/*3 genotypes. However ,the gene polymorphism may be not associated with its hepatotoxicity.

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