1.Thyroid Hormone Network Regulation in MASLD: Mechanisms and Targeted Therapies
Wen-Ping XIAO ; Yang MA ; Heng GUAN ; Sha WAN ; Wen HAN ; Bing-Bing LUO ; Wu-Feng WANG ; Fang LIU
Progress in Biochemistry and Biophysics 2026;53(3):643-661
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide, affecting approximately 32%-38% of the adult population and posing a growing public health burden. MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), progressive hepatic fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis, characterized by an imbalance among de novo lipogenesis, fatty acid β-oxidation, and very-low-density lipoprotein (VLDL)-mediated lipid export. This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression. Among the multiple regulatory pathways involved, thyroid hormone (TH) signaling has emerged as a central regulator of hepatic metabolic homeostasis. The liver is a major peripheral target organ of TH action, where TH predominantly exerts its metabolic effects through thyroid hormone receptor β (TRβ). Large-scale epidemiological studies and meta-analyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence, more severe histological injury, and advanced hepatic fibrosis, suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum. At the molecular level, TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis, enhancement of mitochondrial fatty acid oxidation, and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβ axis and non-genomic signaling pathways. Across different stages of MASLD, TH signaling exerts stage-dependent protective effects. In the steatosis stage, TH improves metabolic flexibility by modulating insulin sensitivity, glucose metabolism, and lipid droplet clearance, thereby alleviating early lipotoxic stress. During progression to MASH, TH attenuates inflammatory amplification by improving mitochondrial homeostasis, suppressing activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and modulating the gut-liver axis microenvironment. In advanced stages, TH signaling influences hepatic stellate cell activation and extracellular matrix deposition, partly through interaction with the transforming growth factor-β (TGF-β)/SMAD pathway, while alterations in intrahepatic TH availability, mediated by dynamic changes in iodothyronine deiodinase 1 (DIO1), contribute to fibrosis progression and hepatocellular dedifferentiation. In hepatocellular carcinoma, coordinated downregulation of TRβ and DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression. The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom, a liver-targeted TRβ‑selective agonist, for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis (F2-F3). This approval represents a landmark transition from mechanistic understanding to metabolism-centered precision therapy in MASLD. Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints, including MASH resolution and fibrosis regression, but also favorably modulates atherogenic lipid profiles, highlighting the therapeutic potential of selectively targeting hepatic TH pathways. This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of TH-based interventions, aiming to inform future mechanistic research and optimize clinical management strategies.
2.The application value of deep learning in imaging studies for predicting the conversion of Alzheimer's disease
Yingmei HAN ; Yijie LI ; Heng ZHANG ; Weiqing LI ; Ze FENG ; Feng WANG
The Journal of Practical Medicine 2025;41(9):1413-1424
Alzheimer's disease(AD),a neurodegenerative disorder,manifests pathological changes in the brain even during the asymptomatic stage.As the pathological burden intensifies,patients experience functional decline in multiple cognitive domains,including memory,language,spatial perception,executive function,and calculation,and may also exhibit emotional abnormalities.Once AD progresses,treatment becomes extremely chal-lenging.Therefore,early diagnosis and accurate prediction of disease conversion are core tasks in the prevention and treatment of AD,and they are also urgent scientific research challenges to be overcome.Deep learning(DL)models demonstrate considerable advantages in the diagnosis,prediction,classification,and feature extraction of AD,offering new hope for solving this challenging problem.This research commences with a concise introduction to the outcomes of AD and the fundamental knowledge of deep learning.Subsequently,it offers an overview of the imaging studies on the utilization of deep learning for predicting disease transformation from two perspectives.Firstly,it systematically summarizes the existing DL models that have demonstrated innovation in the classification and prediction performance of AD.Secondly,it provides a comprehensive outline of the DL fusion models applied to the diagnosis,classification,and prediction of AD.Finally,this paper expounds upon the impending challenges in the research of this domain.This article demonstrates that deep learning models is cutting-edge trends in the ex-ploration of AD research.
3.Preparation and Characterization of Supramolecular Solvent and Its Extraction of Sulfonamide Antibiotics from Milk
Jun-Qiang HAO ; Zhi-Xin ZHANG ; Yu-Heng LI ; Fan-Di ZHAO ; Yang-Yang ZHOU ; Lei ZHAO ; Wei-Jian ZHANG ; Jia-Han XIE ; Zhi-Bing WANG
Chinese Journal of Analytical Chemistry 2025;53(6):976-986
As a cheap and effective antibiotic,sulfonamides are often used in animal husbandry.However,their residues in animal-derived foodstuffs will threaten human health.Consequently,a high-performance liquid chromatography(HPLC)method integrated with supramolecular solvent microextraction was successfully established for simultaneous quantification of sulfonamide residues sulfachlorpyridazine,sulfamethoxazole,sulfamethoxypyridazine and sulfadimethoxine in milk matrices.This approach exhibited prominent characteristics of operational simplicity,environmental sustainability,and high extraction efficiency.The supramolecular solvents prepared by tributyl octylphosphine tetrafluoroborate and tetrahydrofuran were employed as extraction solvents.The analytes underwent isolation and concentration via dispersive liquid-liquid microextraction(DLLME)prior to quantitative determination using high-performance liquid chromatography(HPLC).The composition and microscopic morphology of the supramolecular solvent were characterized through a series of analytical techniques,including phase diagram,Fourier transform infrared spectroscopy,scanning electron microscopy,and inverted fluorescence microscopy and so on.The density and pH value of supramolecular solvents were determined.The extraction conditions were optimized through the one-factor experiments.The experimental results demonstrated that under the optimal extraction conditions,the four kinds of sulfonamide antibiotics exhibited excellent linearity within respective detection range(R2 ≥ 0.9998)and the limits of detection(LOD)were 0.67-1.45 μg/L.Compared with literature methods,this approach offered some advantages such as simplicity of operation and less reagent consumption,and could be used for analysis and detection of sulfonamide antibiotic residues in milk samples.The present method provided technical support for food safety regulation and paved a new way for the application of supramolecular solvents in the field of extraction and separation.
4.Awareness of HCV infection status and willingness for ribonucleic acid testing among hepatitis C cases in four provinces in China
Jiejun YU ; Xiaobin ZHANG ; Ning LI ; Heng TANG ; Shaodong YE ; Jian LI ; Zhongfu LIU ; Dandan YANG ; Jing HAN
Chinese Journal of Epidemiology 2025;46(4):688-694
Objective:To analyze the awareness of HCV infection status and willingness for HCV-RNA testing among hepatitis C cases in four provinces in China and to provide a reference for adjusting HCV prevention and control strategies.Methods:From September 2021 to September 2022, a cross-sectional survey was conducted using stratified random cluster sampling in four provinces (Jiangsu, Henan, Hubei, and Yunnan) in China, with an estimated sample size of 6 468 participants. The questionnaire included sociodemographic information, HCV infection awareness, willingness for HCV-RNA testing, and history of high-risk behaviors from the survey participants. Logistic regression models were used to analyze the factors associated with HCV infection awareness and willingness for HCV-RNA testing among hepatitis C cases. Statistical analysis was performed using R 4.1.3 software.Results:A total of 10 563 hepatitis C cases were surveyed. The awareness rate of HCV infection was 86.74% (9 162/10 563), and the willingness rate for HCV-RNA testing was 85.21% (9 001/10 563). Multivariate logistic regression models analysis showed that the awareness rate of HCV infection was lower among individuals aged ≥60 years, urban residents (with New Rural Cooperative Medical Insurance ), those without a history of blood transfusion, those without a history of paid blood donation, those without a history of injection drug use, and those without a family member with hepatitis C case.The awareness rate was higher among individuals with high or technical secondary school education, college education or above, and those married with a spouse (all P<0.05). In terms of willingness for HCV-RNA testing, it was lower among females, individuals aged ≥60 years, and those without a history of blood transfusion, paid blood donation, or injection drug use. The willingness was higher among farmers or migrant workers, employees of enterprises or institutions, and those in other occupations (all P<0.05). Conclusions:There was room for improvement in the awareness proportion of HCV infection and willingness for HCV-RNA testing among hepatitis C cases in the four provinces of China. More convenient policies and measures should be provided to increase the awareness rate of HCV infection and the willingness to undergo HCV-RNA testing in this population.
5.Bilirubin encephalopathy leads to PARP-1-dependent cell death in the hippocampus of neonatal rats
Junnan HU ; Han LI ; Qiyi HUANG ; Anni PENG ; Yuyuan NIU ; Heng TAN ; Kun DU ; Qian WANG
Chinese Journal of Neuroanatomy 2025;41(5):606-612
Objective:To investigate the role and underlying mechanism of parthanatos death in neonatal SD rats with bilirubin encephalopathy(BE).Methods:Eighty 3-day-old neonatal SD rats were selected and randomly divided into control group and BE group.The BE model was established by intraperitoneal injection of bilirubin solution,and the pathological changes in the hippocampus were observed by hematoxylin-eosin(HE)staining and Nissl staining.The protein expressions of the phosphorylation of the core histone protein H2AX(termed gamma H2AX),poly ADP-ribose polymerasw-1(PARP-1)and apoptosis-inducing factor(AIF)in hippocampus were detected by Western blot.Immuno-fluorescence staining was used to detect the expression and distribution of AIF in hippocampus.Results:Compared with the control group,neonatal SD rats developed jaundice 12 hours after bilirubin injection,accompanied by slow weight gain.HE staining and Nissl staining showed that the hippocampus in BE group were damaged and the content of Nissl bodies was decreased.Western blot results showed that the expression of γ-H2AX protein in hippocampus began to increase at 72 h after modeling(P<0.05),and the levels of PARP-1 and AIF protein in hippocampus increased signif-icantly at 72 h after modeling(P<0.05).Immunofluorescence staining showed increased AIF expression and nuclear translocation.Conclusion:Intraperitoneal injection of bilirubin can induce DNA damage in hippocampal neurons of neonatal SD rats and activate the PARP-1/AIF pathway to cause parthanatos death of hippocampal neurons.
6.Clinical study on the effect of brain-computer interface robot combined with task-oriented training on hand dysfunction after stroke
Han QIN ; Yongmei ZHU ; Qianhui TIAN ; Tianning ZHANG ; Shiwei XU ; Xiaoyan ZHAO ; Heng ZHANG ; Xuan SUN ; Hui ZHAO
Chinese Journal of Cerebrovascular Diseases 2025;22(9):612-621
Objective To observe the impact of brain-computer interface(BCI)robot combined with task-oriented training(TOT)on hand function and activities of daily living in stroke patients.Methods A total of 40 patients with subacute stroke who were hospitalized in the Department of Rehabilitation Medicine of Anhui No.2 Province People's Hospital from December 2022 to December 2024 were prospectively and consecutively included in this study.The stroke patients were randomly assigned to the experimental group and the control group using the random number table method,with 20 cases in each group.Baseline data were collected from all patients,including gender,age,personal history(smoking,drinking),past medical history(hypertension,diabetes),stroke type(hemorrhagic stroke,ischemic stroke),hemiplegia side(left,right),disease course,stroke location(basal ganglia,internal capsule),and admission assessment indicators(including kinesthetic and visual imagery questionnaire[KVIQ-20]score,mini-mental state examination[MMSE]score and National Institutes of Health stroke scale[NIHSS]score).Both groups of patients received conventional rehabilitation training and TOT.The experimental group then underwent BCI robot training combined with TOT on this basis.Both groups received treatments for 4 weeks,and the upper limb and hand functions of all patients were evaluated using the Fugl-Meyer upper extremity function assessment scale(FMA-UE),the wrist-hand part of the FMA-UE scale(FMA-WH),the Wolf motor function test(WMFT),and the modified Ashworth scale(MAS)before and after the treatment;the hand function related part(feeding[10 score],bathing[5 score],dressing[10 score],grooming[5 score],and toilet using[10 score])of modified Barthel index(MBI)was used to assess the patients'hand dexterity to perform daily activities.Results(1)No statistically significant differences were found in the baseline data between the two groups of patients(all P>0.05).(2)Before treatment,the scores of FMA-UE,FMA-WH,WMFT,MAS and hand function related score of MBI in the experimental group were(18.75±7.38),(2.95±1.54),(26.90±8.69),(1.10±0.66),and(15.45±1.82)respectively,while those in the control group were(15.90±5.39),(2.25±1.12),(24.15±6.78),(1.25±0.60),and(15.65±3.12)respectively.There were no statistically significant differences in the scores of FMA-UE,FMA-WH,WMFT,MAS and hand function related score of MBI between the two groups before treatment(all P>0.05).After 4 weeks of treatment,the scores of FMA-UE,FMA-WH,WMFT,MAS and hand function related score of MBI in the experimental group were(27.10±7.76),(5.75±2.97),(40.85±10.19),(0.73±0.57),and(21.15±2.66)respectively,while those in the control group were(21.25±5.29),(4.00±1.49),(31.85±7.60),(0.73±0.64),and(17.40±3.14)respectively.The time main effects(Ftime values were 925.061,138.138,624.635 and 405.986 respectively,all P<0.01),group main effects(Fgroup values were 4.460,4.562,5.011 and 4.411 respectively,all P<0.05),and the interaction effects of time and group(Ftime×group values were 44.358,7.356,52.506 and 114.128 respectively,all P<0.05)of FMA-UE,FMA-WH,WMFT and hand function related score of MBI scores were all significant.The time main effect of MAS scores was significant(Ftime value was 59.478,P<0.01),while the group main effect(Fgroup value was 0.162,P>0.05),the interaction effects of time and group(Ftime×group value was 1.652,P>0.05)were not significant.Conclusion The combined task-oriented training with BCI robots can improve the upper limb and hand functions of stroke patients,enhance their ability to perform daily activities,and the effect is superior to that of single task-oriented training.
7.Optimal b-Value Sets Based on Intravoxel Incoherent Motion in Pulmonary Solid Benign and Malignant Lesions
Wei WEI ; Heng LI ; Na ZHAO ; Chanjuan YU ; Xiuzheng YUE ; Zhiwei SHEN ; Xiangfei CHEN ; Sheng ZHANG ; Xiao YANG ; Yuedong HAN
Chinese Journal of Medical Imaging 2025;33(8):834-839
Purpose To quantitatively compare the diffusion parameters of mono-and biexponential diffusion-weighted imaging models,and to obtain optimal sets of b-values in diffusion-weighted MRI for obtaining monoexponential apparent diffusion coefficient(ADC)close to perfusion-insensitive intravoxel incoherent motion(IVIM)model ADC(ADCIVIM)in identifying of pulmonary solid benign and malignant lesions.Materials and Methods IVIM was performed in 40 patients with solid nodule and masse in Xi'an Gaoxin Hospital from July 2021 to August 2022 using a 3.0T MR imager.Two experienced diagnostic radiologists subjectively evaluated the IVIM images.A single index model was used to calculate ADC values(ADC0-1 000,ADC20-1 000,ADC50-1 000,ADC80-1 000,ADC150-1 000,ADC300-1 000,ADC500-1 000,ADC300,500,1 000,ADC300,800,1 000,ADC300,500,ADC300,800 and ADC300,1 000).The reference standard ADCIVIM value were calculated using a double-exponential model.The physician's measurements between two physicians were measured.The malignant and benign groups were compared and receiver operator characteristic curve for all parameters were analyzed.Results The measurement consistency of ADC values under b value sets and ADCIVIM was very good,and the intraclass correlation coefficient was more significant than 0.75.The differences between ADCIVIM and ADC values in each b group were statistically significant(t=-6.016--2.500,all P<0.05).The area under the curve(AUC)of ADCIVIM was the largest(0.906),with an optimal threshold of 1.271×10-3 mm2/s,a sensitivity of 80.0%and a specificity of 93.0%.The diagnostic efficacy close to ADCIVIM were ADC300,800(AUC=0.891),ADC50-1 000(AUC=0.827)and ADC300,800,1 000(AUC=0.795),respectively.The optimal threshold of ADC300,800 was 1.140×10-3 mm2/s,the sensitivity and specificity were 80.0%and 93.7%,respectively.Conclusion Combining b-values 300 s/mm2 and 800 s/mm2 is recommended as routine scanning parameters for identifying the insensitive monoexponential ADC between benign and malignant solid pulmonary lesions.
8.MR Three-Dimensional Multi-Echo Ultrashort Echo Time Quantitative Technique in Differential Diagnosis in Benign and Malignant Pulmonary Nodules and Masses
Heng LI ; Wei WEI ; Xiao YANG ; Na ZHAO ; Xiuzheng YUE ; Yuedong HAN
Chinese Journal of Medical Imaging 2025;33(10):1115-1119
Purpose To explore the value of quantitative parameters(T2* value,R2* value)of three-dimensional multi-echo ultrashort echo time technique for the differential diagnosis of benign and malignant pulmonary nodules and masses(PNMs).Materials and Methods The MRI data of 68 patients with PNMs in Xi'an Gaoxin Hospital from July 2021 to October 2022 were retrospectively analyzed,and PNMs were grouped into benign(34 cases)and malignant(34 cases)categories using histopathology or clinical follow-up as the reference standard.Two observers respectively outlined the regions of interest on three-dimensional multi-echo ultrashort echo time-T2* and R2* maps,and quantitatively measured the T2* and R2* values.The intraclass correlation coefficient(ICC)was used to evaluate the consistency of the measured values.Differences in the above indicators between the two groups of PNMs were analyzed,and their diagnostic efficacy was assessed.The predictive probability of the combined two indicators was computed,the receiver operating characteristic curve was plotted,and the area under the curve(AUC)was calculated.Results The measurement results of each parameter of PNMs in the benign and malignant groups by the two observers were consistent(ICC>0.75).The T2* value of the malignant group was higher than that of the benign group(Z=-5.158,P<0.001),and the R2* value was lower than that of the benign group(Z=-4.845,P<0.001),and the differences were statistically significant.The AUC of the T2* value was 0.864(95%CI 0.775-0.953,P<0.001),with a maximum Youden index of 0.677,a threshold of 9.675 ms,a sensitivity of 76.5%,and a specificity of 91.2%.The AUC of the R2* value was 0.842(95%CI 0.746-0.937,P<0.001),with a maximum Youden index of 0.647,and a threshold of 109.15/s,with a sensitivity of 73.5%and a specificity of 91.2%.The AUC of the combined diagnosis of T2* and R2* values was 0.867(95%CI 0.779-0.955,P<0.001),with a maximum Youden index of 0.677,a sensitivity of 82.4%,and a specificity of 85.3%.There was no statistically significant difference in the pairwise comparison of T2* values,R2* values,and their combined AUC(all P>0.05).Conclusion The T2* value and R2* value of the three-dimensional multi-echo ultrashort echo time technique,as well as the combination of the two indicators,are all helpful in differentiating benign and malignant PNMs,providing imaging support for the preoperative non-invasive and precise differentiation of PNMs and optimizing clinical diagnosis and treatment decisions.
9.Structural insights into the distinct ligand recognition and signaling of the chemerin receptors CMKLR1 and GPR1.
Xiaowen LIN ; Lechen ZHAO ; Heng CAI ; Xiaohua CHANG ; Yuxuan TANG ; Tianyu LUO ; Mengdan WU ; Cuiying YI ; Limin MA ; Xiaojing CHU ; Shuo HAN ; Qiang ZHAO ; Beili WU ; Maozhou HE ; Ya ZHU
Protein & Cell 2025;16(5):381-385
10.Comparison and evaluation of three different methods for preparing rat models of lumbar disc herniation
Hao YIN ; Meiqi JI ; Zhixiang HU ; Han WU ; Heng LYU ; Shengyun LI ; Lei LI ; Chuntao ZHAI ; Yue LYU
Chinese Journal of Tissue Engineering Research 2025;29(14):2930-2936
BACKGROUND:Currently,there are various rat models of lumbar disc herniation used in experiments,each with its own advantages and disadvantages.The most common modeling methods include autologous nucleus pulposus transplantation and annulus fibrosus puncture models.OBJECTIVE:To establish two autologous nucleus pulposus transplantation models(with spinous process and mastoid process excision and with transverse process and mastoid process excision)as well as an annulus fibrosus puncture model,and to compare and evaluate the characteristics of the three models.METHODS:Forty male adult Sprague-Dawley rats were randomly divided into four groups(n=10 per group):sham surgery group,spinous process group,transverse process group,and annulus fibrosus puncture group.In the sham surgery group,surgical preparation was performed,the skin was incised,and the spinous process was exposed,and then sutured.In the spinous process group,L5 spinous process and transverse process were excised,and two pieces of tail nucleus pulposus were placed in the intervertebral foramen.In the transverse process group,L5 transverse process and transverse process were excised,and two pieces of tail nucleus pulposus were placed in the intervertebral foramen.In the annulus fibrosus puncture group,the transverse process was excised and annulus fibrosus puncture and intervertebral disc injection of interleukin 1β were then performed.Thermal paw withdrawal latencies were tested before and after modeling.Lumbar spine MRI was performed 2 weeks after modeling.Pathological changes in the intervertebral discs were observed using hematoxylin-eosin staining and safranin-O-fast green staining.Immunofluorescence was used to observe CD68+positive expression.RESULTS AND CONCLUSION:(1)Thermal withdrawal threshold testing results showed that compared with the sham surgery group,pain sensitivity and tolerance time of rats decreased significantly after modeling(P<0.05).(2)Lumbar spine MRI images showed that the spinous process and transverse process groups had obvious protrusion of nucleus pulposus tissue,which more closely resembled MRI images of patients with common lumbar disc herniation.(3)Hematoxylin-eosin staining revealed that compared with the sham surgery group,nucleus pulposus tissues in the model groups showed varying degrees of degeneration,inflammatory cell infiltration,and degradation of spinal cord cells,with the appearance of cystic changes,among which the annulus fibrosus puncture group had the most severe pathological changes.(4)Safranin-O-fast green staining showed that compared with the sham surgery group,the boundaries of nucleus pulposus tissues in the three model groups were blurred,with extensive inflammatory reactions and varying degrees of degeneration in the annulus fibrosus.(5)CD68+immunofluorescence staining results showed that compared with the sham surgery group,the expression of CD68+in the model groups was higher and more widespread,with the annulus fibrosus puncture model showing the highest expression.All the three methods could be used to effectively establish rat models of lumbar disc herniation,with the annulus fibrosus puncture model established after excision of the transverse process being superior to the autologous nucleus pulposus transplantation model(spinous process+mastoid process),and the first two models being superior to the autologous nucleus pulposus transplantation model(transverse process+mastoid process).

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