1.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
2.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
3.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
4.Research on attention-enhanced networks for subtype classification of age-related macular degeneration in optical coherence tomography.
Minghui CHEN ; Wenyi YANG ; Shiyi XU ; Yanqi LU ; Zhengqi YANG ; Fugang LI ; Zhensheng GU
Journal of Biomedical Engineering 2025;42(5):901-909
Subtype classification of age-related macular degeneration (AMD) based on optical coherence tomography (OCT) images serves as an effective auxiliary tool for clinicians in diagnosing disease progression and formulating treatment plans. To improve the classification accuracy of AMD subtypes, this study proposes a keypoint-based, attention-enhanced residual network (KPA-ResNet). The proposed architecture adopts a 50-layer residual network (ResNet-50) as the backbone, preceded by a keypoint localization module based on heatmap regression to outline critical lesion regions. A two-dimensional relative self-attention mechanism is incorporated into convolutional layers to enhance the representation of key lesion areas. Furthermore, the network depth is appropriately increased and an improved residual module, ConvNeXt, is introduced to enable comprehensive extraction of high-dimensional features and enrich the detail of lesion boundary contours, ultimately achieving higher classification accuracy of AMD subtypes. Experimental results demonstrate that KPA-ResNet achieves significant improvements in overall classification accuracy compared with conventional convolutional neural networks. Specifically, for the wet AMD subtypes, the classification accuracies for inactive choroidal neovascularization (CNV) and active CNV reach 92.8% and 95.2%, respectively, representing substantial improvement over ResNet-50. These findings validate the superior performance of KPA-ResNet in AMD subtype classification tasks. This work provides a high-accuracy, generalizable network architecture for OCT-based AMD subtype classification and offers new insights into integrating attention mechanisms with convolutional neural networks in ophthalmic image analysis.
Tomography, Optical Coherence/methods*
;
Humans
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Macular Degeneration/diagnostic imaging*
;
Neural Networks, Computer
5.Value of ion channel genes in epilepsy treatment
Wenjie HAN ; Zhensheng LI ; Jianjie KANG ; Bingmei DENG
Chinese Journal of Neuromedicine 2024;23(3):240-245
By gene sequencing methods, such as targeted sequencing, whole exome sequencing (WES) and whole genome sequencing (WGS), about 1,000 epilepsy-related genes have been identified recently; and ion channel related genes are the most common genes being studied; about 25% single-gene inherited epilepsy is associated with ion channel gene variants. This article reviews the value of ion channel genes in epilepsy treatment so as to improve the understanding of epilepsy related ion channel genes and further optimize the treatment strategy of epilepsy.
6.Risk factors of depression and anxiety in epilepsy patients and their relationship with quality of life
Wenjie HAN ; Youtian ZHOU ; Zhensheng LI ; Jianjie KANG ; Bingmei DENG
The Journal of Practical Medicine 2024;40(4):460-465
Objective To explore the risk factors of depression and anxiety in adult patients with epilepsy and their relationship with quality of life.Methods From May 2022 to January 2023,patients diagnosed with epilepsy(aged≥18 years)in the department of neurology of our hospital were collected.General demographic data and disease-related information were recorded.Quality of life,depression and anxiety scales were measured in all patients.SPSS26.0 software was used for multiple linear regression analysis,multiple ordered Logistic regression analysis,rank sum test,Pearson correlation analysis,etc.Results Among the 111 patients,49.5%had depression and 43.2%had anxiety.Depression score and anxiety score were correlated with attack type,attack frequency,quality of life and right temporal lobe,and there was a significant negative correlation between life quality score and anxiety and depression score(P<0.01).Seizure frequency,seizure type and right temporal lobe were common risk factors for depression and anxiety in patients with epilepsy(P<0.05).Conclusion Epileptic depression and anxiety were affected by seizure frequency and seizure type,and this bad mood further affected the quality of life of patients.No clear link has been found between the lateralization of seizures and the presence of depression and anxiety states,and further research is needed.
7.Clinical validation of the safety and efficacy of sodium hyaluronate gel DX23 in the treatment of midface depression
Yan JIN ; Zhensheng HU ; Zhihua ZHANG ; Pei LIU ; Wenzhi LI
Chinese Journal of Plastic Surgery 2024;40(11):1175-1183
Objective:To investigate the efficacy and safety of injectable modified sodium hyaluronate gel DX23 in filling and treating midface depression.Methods:A prospective, randomized, multicenter, "no treatment" controlled study was conducted. Patients with midface depression who were treated from March 2019 to February 2021 at Beijing Anzhen Hospital Affiliated to Capital Medical University, Qilu Hospital of Shandong University, and Jining First People’s Hospital were enrolled. Patients were randomized using a stratified block randomization method with a random function list. The experimental group received injectable modified sodium hyaluronate gel DX23 to treat midface depression. The concentration of sodium hyaluronate in DX23 was 23 mg/ml. The syringe was inserted perpendicularly to the skin at a 90-degree angle, and the injection layers were the superficial periosteum or the subcutaneous layer. The injection volume ranged from 1 to 6 ml. The control group received no treatment. The upper boundary of the midface extended outward from the zygomatic arch to the upper margin of the helix and inward to the line connecting the outer canthus. The lower boundary was the line connecting the corner of the mouth to the earlobe. Researchers used the midface aesthetic scales (MAS) response rate at 6 months post-injection as the primary indicator to evaluate the efficacy in improving the severity of midface depression. A reduction of 1 point in the MAS score compared to pre-treatment was considered a response, i. e., effective. Secondary indicators included the MAS response rates at 6 and 12 months after the last treatment (MAS response rate=number of MAS responders/total cases × 100%), the average change in three-dimensional midface volume images, the global aesthetic improvement scale (GAIS) response rate, patient satisfaction regarding the degree of improvement in midface volume, and monitoring of adverse reactions. Data analysis was performed using SPSS 25.0, SAS 9.04, and StataIC 15.0 software. The full analysis set (FAS) and the per-protocol set (PPS) were selected for analysis. Inferential analysis used t-tests and chi-square tests, with P<0.05 considered statistically significant. Results:A total of 164 patients were enrolled. The experimental group included 134 patients (7 males and 127 females) with an average age of 43.0±9.7 years (ranging from 21.6 to 66.6 years). The control group included 30 patients (5 males and 25 females) with an average age of 39.3±11.1 years (ranging from 25.6 to 43.5 years). The experimental group received bilateral midface depression filling, with an initial use of injectable modified sodium hyaluronate gel DX23 at a volume of (4.07±1.28) ml. In the experimental group, 3 cases were lost to follow-up at 30 days, 2 cases at 60 days, and 10 cases were excluded due to protocol violations. Fifteen patients entered FAS but not PPS. Ultimately, 119 patients completed the trial. The MAS response rates in the experimental group at 6 and 12 months post-treatment were 94.96% (113/119) and 56.30% (67/119), respectively. The control group’s MAS response rate at 6 months was 3.33% (1/30). At the 6-month follow-up post-treatment, the GAIS response rates evaluated by researchers and patients in the experimental group were 97.48% (116/119) (PPS) and 97.69% (27/30) (FAS), respectively. In the control group, the GAIS response rate evaluated by researchers was 3.33% (1/30) (FAS, PPS), and the patient GAIS response rate was 0% (0/30) (FAS, PPS). There were statistically significant differences between the two groups in both researcher and patient GAIS response rates (both P<0.01). At 6 months post-injection, comparisons of midface volume changes from baseline between the experimental and control groups showed statistically significant differences [(1.65±1.40) ml (PPS) vs. (0.12±0.85) ml; (1.55±1.44) ml (FAS) vs. (0.12±0.85) ml; both P<0.001]. At the 6-month follow-up in the experimental group, 1 case was lost to follow-up. In the PPS, 81 patients were "satisfied, " 34 were "very satisfied, " and 3 were "neutral." In the control group, 29 patients were "neutral, " and 1 was "dissatisfied." A total of 128 patients in the experimental group experienced injection site reactions, including swelling, hardness, tenderness, pain, lumps (protrusions), and bruising. Over 75% of patients resolved spontaneously within 8 days. Three cases received hot compress treatment and resolved within 28 days. One case experienced swelling of the left lower eyelid 1 day after injection, which resolved after local compression for 3 months. In the control group, 1 case developed circulatory ischemia and carotid atherosclerosis 12 months after the trial began. Conclusion:Injectable modified sodium hyaluronate gel DX23 corrects midface depression through local volume augmentation and is characterized by safety and durability.
8.Myelin oligodendrocyte glycoprotein antibody-associated disease:a clinical analysis of 14 cases
Bingmei DENG ; Zhuo LIU ; Wei XIANG ; Wenjie HAN ; Youtian ZHOU ; Zhensheng LI ; Tiegen XIONG ; Jianjie KANG
Journal of Army Medical University 2024;46(12):1434-1440
Objective To investigate the clinical and imaging characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease(MOGAD).Methods The clinical symptoms,MRI features,results of laboratory tests and clinical prognosis of 14 MOGAD patients who were hospitalized in our hospital from June 2016 to June 2022 were collected and retrospectively analyzed.Their clinical and imaging characteristics were summarized and discussed.Results Among the 14 enrolled patients,there were 10 males and 4 females,with a male to female ratio of 2.5∶1.Their age of first onset was<18 years in 3 cases,18~45 years in 8 cases,and>45 years in 3 cases.Optic neuritis(10/14,71.43%)was the most common clinical type,followed by encephalitis or meningoencephalitis(9/14,64.29%),brainstem encephalitis(5/14,35.71%)and myelitis(5/14,35.71%).Visual impairment(10/14,71.43%)was the most common clinical symptom,followed by headache in 8 cases(8/14,57.14%),fever in 6 cases(6/14,42.86%),dizziness in 6 cases(6/14,42.86%),parethesia in 5 cases(5/14,35.71%),and seizures,limb paralysis,sphincter dysfunction,ataxia,and vomit were all in 4 cases(4/14,28.57%).Four patients(4/14,28.57%)had a history of upper respiratory tract infection before MOGAD onset.There were 10 patients undergoing cerebrospinal fluid(CSF)test,and 8 of them had abnormal results,including 2 patients(2/10,20%)of increased pressure,8 patients(8/10,80%)of larger WBC count in CSF,and 5 patients(5/10,50%)of elevated total protein in CSF.MRI displayed multiple lesion involvement,and there were 7 cases(7/14,50.00%)in cortical/subcortical white matter,6 cases in brainstem(6/14,42.86%),5 cases in optic nerve(5/14,35.71%),4 cases in spinal cord(4/14,28.57%).The hippocampus,thalamus,basal ganglia,and paraventricular white matter were involved in 3 cases(3/14,21.43%),respectively,and the cerebellum and corpus callosum were in 2 cases(2/14,14.29%),respectively.MRI lesions demonstrated patchy hyperintensity on T2 WI and T2 FLAIR,with patchy,nodular and linear enhancement.Among the 10 patients undergoing visual evoked potential(VEP)test,abnormalities were detected in 9 cases(9/10,90%),and 8(8/10,80%)had bilateral visual pathway abnormalities.Eight patients(8/14,57.14%)experienced relapse and remission course.Both methylprednisolone pulse therapy and immunoglobulin modulation therapy were effective in the acute phase.Five patients with relapsed remission presented a significant reduction in recurrence after immunosuppressants.Conclusion MOGAD is manifested with various clinical features,with vision loss,headache,fever and dizziness more common.MRI lesions of MOGAD involve cerebral cortex,subcortical white matter,brainstem,and optic nerve,etc.Patchy hyperintesive signals are observed on T2WI and T2 FLAIR,and some lesions can be enhanced.Corticosteroid pulse therapy and immunoglobulin therapy show effective treatment in the acute phase,and immunosuppressants in the remission phase can reduce relapse.
9.Clinical validation of the safety and efficacy of sodium hyaluronate gel DX23 in the treatment of midface depression
Yan JIN ; Zhensheng HU ; Zhihua ZHANG ; Pei LIU ; Wenzhi LI
Chinese Journal of Plastic Surgery 2024;40(11):1175-1183
Objective:To investigate the efficacy and safety of injectable modified sodium hyaluronate gel DX23 in filling and treating midface depression.Methods:A prospective, randomized, multicenter, "no treatment" controlled study was conducted. Patients with midface depression who were treated from March 2019 to February 2021 at Beijing Anzhen Hospital Affiliated to Capital Medical University, Qilu Hospital of Shandong University, and Jining First People’s Hospital were enrolled. Patients were randomized using a stratified block randomization method with a random function list. The experimental group received injectable modified sodium hyaluronate gel DX23 to treat midface depression. The concentration of sodium hyaluronate in DX23 was 23 mg/ml. The syringe was inserted perpendicularly to the skin at a 90-degree angle, and the injection layers were the superficial periosteum or the subcutaneous layer. The injection volume ranged from 1 to 6 ml. The control group received no treatment. The upper boundary of the midface extended outward from the zygomatic arch to the upper margin of the helix and inward to the line connecting the outer canthus. The lower boundary was the line connecting the corner of the mouth to the earlobe. Researchers used the midface aesthetic scales (MAS) response rate at 6 months post-injection as the primary indicator to evaluate the efficacy in improving the severity of midface depression. A reduction of 1 point in the MAS score compared to pre-treatment was considered a response, i. e., effective. Secondary indicators included the MAS response rates at 6 and 12 months after the last treatment (MAS response rate=number of MAS responders/total cases × 100%), the average change in three-dimensional midface volume images, the global aesthetic improvement scale (GAIS) response rate, patient satisfaction regarding the degree of improvement in midface volume, and monitoring of adverse reactions. Data analysis was performed using SPSS 25.0, SAS 9.04, and StataIC 15.0 software. The full analysis set (FAS) and the per-protocol set (PPS) were selected for analysis. Inferential analysis used t-tests and chi-square tests, with P<0.05 considered statistically significant. Results:A total of 164 patients were enrolled. The experimental group included 134 patients (7 males and 127 females) with an average age of 43.0±9.7 years (ranging from 21.6 to 66.6 years). The control group included 30 patients (5 males and 25 females) with an average age of 39.3±11.1 years (ranging from 25.6 to 43.5 years). The experimental group received bilateral midface depression filling, with an initial use of injectable modified sodium hyaluronate gel DX23 at a volume of (4.07±1.28) ml. In the experimental group, 3 cases were lost to follow-up at 30 days, 2 cases at 60 days, and 10 cases were excluded due to protocol violations. Fifteen patients entered FAS but not PPS. Ultimately, 119 patients completed the trial. The MAS response rates in the experimental group at 6 and 12 months post-treatment were 94.96% (113/119) and 56.30% (67/119), respectively. The control group’s MAS response rate at 6 months was 3.33% (1/30). At the 6-month follow-up post-treatment, the GAIS response rates evaluated by researchers and patients in the experimental group were 97.48% (116/119) (PPS) and 97.69% (27/30) (FAS), respectively. In the control group, the GAIS response rate evaluated by researchers was 3.33% (1/30) (FAS, PPS), and the patient GAIS response rate was 0% (0/30) (FAS, PPS). There were statistically significant differences between the two groups in both researcher and patient GAIS response rates (both P<0.01). At 6 months post-injection, comparisons of midface volume changes from baseline between the experimental and control groups showed statistically significant differences [(1.65±1.40) ml (PPS) vs. (0.12±0.85) ml; (1.55±1.44) ml (FAS) vs. (0.12±0.85) ml; both P<0.001]. At the 6-month follow-up in the experimental group, 1 case was lost to follow-up. In the PPS, 81 patients were "satisfied, " 34 were "very satisfied, " and 3 were "neutral." In the control group, 29 patients were "neutral, " and 1 was "dissatisfied." A total of 128 patients in the experimental group experienced injection site reactions, including swelling, hardness, tenderness, pain, lumps (protrusions), and bruising. Over 75% of patients resolved spontaneously within 8 days. Three cases received hot compress treatment and resolved within 28 days. One case experienced swelling of the left lower eyelid 1 day after injection, which resolved after local compression for 3 months. In the control group, 1 case developed circulatory ischemia and carotid atherosclerosis 12 months after the trial began. Conclusion:Injectable modified sodium hyaluronate gel DX23 corrects midface depression through local volume augmentation and is characterized by safety and durability.
10.Fibroblast growth factor 21 (FGF21) attenuates tacrolimus-induced hepatic lipid accumulation through transcription factor EB (TFEB)-regulated lipophagy.
Zhensheng ZHANG ; Li XU ; Xun QIU ; Xinyu YANG ; Zhengxing LIAN ; Xuyong WEI ; Di LU ; Xiao XU
Journal of Zhejiang University. Science. B 2023;24(6):485-495
Tacrolimus (TAC), also called FK506, is one of the classical immunosuppressants to prevent allograft rejection after liver transplantation. However, it has been proved to be associated with post-transplant hyperlipemia. The mechanism behind this is unknown, and it is urgent to explore preventive strategies for hyperlipemia after transplantation. Therefore, we established a hyperlipemia mouse model to investigate the mechanism, by injecting TAC intraperitoneally for eight weeks. After TAC treatment, the mice developed hyperlipemia (manifested as elevated triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c), as well as decreased high-density lipoprotein cholesterol (HDL-c)). Accumulation of lipid droplets was observed in the liver. In addition to lipid accumulation, TAC induced inhibition of the autophagy-lysosome pathway (microtubule-associated protein 1 light chain 3β (LC3B) II/I and LC3B II/actin ratios, transcription factor EB (TFEB), protein 62 (P62), and lysosomal-associated membrane protein 1 (LAMP1)) and downregulation of fibroblast growth factor 21 (FGF21) in vivo. Overexpression of FGF21 may reverse TAC-induced TG accumulation. In this mouse model, the recombinant FGF21 protein ameliorated hepatic lipid accumulation and hyperlipemia through repair of the autophagy-lysosome pathway. We conclude that TAC downregulates FGF21 and thus exacerbates lipid accumulation by impairing the autophagy-lysosome pathway. Recombinant FGF21 protein treatment could therefore reverse TAC-caused lipid accumulation and hypertriglyceridemia by enhancing autophagy.
Animals
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Mice
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Tacrolimus
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Liver
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Cholesterol, LDL
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Autophagy
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Disease Models, Animal

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