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.Establishment of preparation process and quality standard for Zhenggu Pills
Wen-ming ZHANG ; Zi-fang FENG ; Li-hong GU ; Ping QIN ; Zhen-hua BIAN ; Min-min HU ; Xiao-wei CHEN
Chinese Traditional Patent Medicine 2025;47(9):2863-2869
AIM To establish the preparation process and quality standard for Zhenggu Pills.METHODS With decoction time,decoction frequency and water addition as influencing factors,comprehensive score for extract yield and transfer rates of epicatechin and naringin as an evaluation index,the decoction process was optimized by orthogonal test.With sugarless paste relative density,medicinal powder fineness,sugarless paste-corn starch ratio,drying temperature and drying time as influencing factors,soft material traits,pill formability,moisture and disintegration time limit as evaluation indices,the formability process was optimized by single factor test.TLC was adopted in the qualitative identification of Dipsaci Radix,salt-processed Psoraleae Fructus,cooked Rhei Radix et Rhizoma and Notoginseng Radix et Rhizoma.HPLC was used for the content determination of paeoniflorin and naringin.RESULTS The optimal decoction process was determined to be 0.5 h for decoction time,two times for decoction frequency,and 10 times for water addition,the comprehensive score was 0.93.The optimal formability process was determined to be 1.21-1.22 for sugarless paste relative density,80 mesh for medicinal powder fineness,1∶0.17-1∶0.18 for sugarless paste-corn starch ratio,70 ℃ for drying temperature,and 24 h for drying time,good soft material traits and pill formability were observable,and moisture and disintegration time limit accored with 2020 edition of Chinese Pharmacopoeia requirements.The TLC spots were clear without negative interference.Two constituents showed good linear relationships within 61.30-490.41 μg/mL(r=0.999 8)and 3.27-26.18 μg/mL(r=0.999 8),whose average recoveries were 100.15%and 98.15%with the RSDs of 0.55%and 2.30%,respectively.CONCLUSION This stable,reliable and specific method can be used for the production and quality evaluation of Zhenggu Pills.
3.Establishment of quantitative models for effective components in Yishen Xiezhuo Mixture
Zi-fang FENG ; Min-min HU ; Xiao-wei CHEN ; Wen-ming ZHANG ; Li-hong GU ; Ping QIN ; Yi PENG ; Zhen-hua BIAN ; Qing-you YANG ; Tu-lin LU
Chinese Traditional Patent Medicine 2025;47(10):3177-3184
AIM To establish the quantitative models for gallic acid,mononucleoside,loganin,resveratrol,and rhein in Yishen Xiezhuo Mixture.METHODS HPLC was adopted in the content determination of various effective components,after which the near-infrared spectroscopy(NIRS)data were collected in 128 batches of samples and pretreatment was conducted,competitive adaptive reweighting sampling(CARS)algorithm was used for screening wavelength,partial least square method(PLS)regression analysis was performed.RESULTS There were no significant differences between the predicted values obtained by PLS models and measured values obtained by HPLC for various effective components(P>0.05).CONCLUSION The quantitative models established by NIRS combined with chemometrics display good predictive performance,which can be used for the rapid determination of effective components in Yishen Xiezhuo Mixture,and provide a reference for the rapid monitoring of other traditional Chinese medicine preparations in production processes.
4.Terms Related to The Study of Biomacromolecular Condensates
Ke RUAN ; Xiao-Feng FANG ; Dan LI ; Pi-Long LI ; Yi LIN ; Zheng WANG ; Yun-Yu SHI ; Ming-Jie ZHANG ; Hong ZHANG ; Cong LIU
Progress in Biochemistry and Biophysics 2025;52(4):1027-1035
Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.
5.Analysis of Clinical Characteristics and Risk Factors for Bone Lesions in Patients with Multiple Myeloma
Chen-Yang LI ; Qi-Ke ZHANG ; Xiao-Fang WEI ; You-Fan FENG ; Yuan FU ; Qiao-Lin CHEN ; Wen-Jie ZHANG ; Yuan-Yuan ZHANG ; Shao-Hua ZHANG ; Shang-Yi ZHANG ; Jie LIU
Journal of Experimental Hematology 2025;33(6):1635-1639
Objective:To investigate the clinical characteristics of patients with multiple myeloma(MM)complicated by bone lesions and the risk factors associated with bone lesions.Methods:The clinical data of 294 newly diagnosed MM patients in Gansu Provincial Hospital from January 2017 to June 2021 were retrospectively analyzed.The patients were divided into the bone lesion group(154 cases)and the non-bone lesions group(140 cases)based on the presence of absence of bone lesions at diagnosis.The general data and laboratory parameters were compared between the two groups.The risk factors for bone lesions in MM patients were analyzed by logistic regression analysis,and the characteristic(ROC)curves were plotted to assess the predictive value of each risk factor for the occurrence of bone lesions in MM patients.Results:Compared to the non-bone lesion group,the bone lesion group had significantly higher serum calcium levels and significantly greater proportions of patients with Durie-Salmon(DS)stage Ⅲ,and bone pain(all P<0.05).Logistic regression analysis showed that elevated serum calcium(OR=5.135,95%CI:1.931-13.653,P=0.001),DS stage Ⅲ(OR=1.841,95%CI:1.019-3.328,P=0.043),and bone pain(OR=8.208,95%CI:4.761-14.151,P<0.001)were independent risk factors for bone lesions in MM patients.ROC curve analysis showed that serum calcium(AUC=0.619,95%CI:0.555-0.683,P<0.001)and bone pain(AUC=0.743,95%CI:0.692-0.793,P<0.001)had predictive value for bone lesions in MM patients.Conclusion:MM patients have a high incidence of bone lesions,and active monitoring and management of risk factors may improve treatment outcomes and prognosis.
6.Correlation of knee joint asymmetry with balance and walking ability in hemiplegic stroke patients
Zheng-Hua XIAO ; Jiang MA ; Hong LI ; Fang WANG ; Li-Ying GUO ; Xiao-Lin TAO ; Feng ZHANG ; Ya-Yong LI ; Xiao-Li YAN
Medical Journal of Chinese People's Liberation Army 2025;50(2):134-140
Objective To explore the correlation of bilateral knee joint strength asymmetry with balance,walking ability,and motor function in hemiplegic stroke patients,providing a reference for clinical assessment of stroke patients.Methods A total of 46 hemiplegic stroke patients admitted to the Rehabilitation Medicine Department of People's Hospital of Shijiazhuang from February to December 2023 were selected.According to the Berg Balance Scale(BBS)scores,patients were divided into Group A(BBS score≤20,n=23)and Group B(BBS score>20,n=23).The peak torque and differences of bilateral knee flexors and extensors were compared between two groups.Isokinetic technology was used to assess the differences in peak torque of bilateral knee joints at 60°/s and 120°/s.BBS,Functional Ambulation Classification(FAC),and Fugl-Meyer Assessment of Lower Extremity(FMA-LE)were used to evaluate patients'balance,walking ability,and lower limb motor function.The correlation between bilateral knee joint peak torque and its difference with the scores of three functional scales was analyzed.Results The peak torque of knee flexors and extensors at 60°/s in group A was significantly lower than that in group B(P<0.05).At both 60°/s and 120°/s the differences in peak torque between the healthy and affected sides of knee flexors and extensors were greater than those in group B(P<0.05).At 60°/s,the difference in peak torque of bilateral knee extensors in hemiplegic stroke patients was negatively correlated with the scores of BBS,FAC,and FMA-LE(r=-0.569,-0.582,-0.606,P<0.01),as did the knee flexors(r=-0.534,-0.386,-0.458,P<0.05).At 120°/s,similar negative correlations were observed for both knee extensors(r=-0.304,-0.304,-0.443,P<0.05)and flexors(r=-0.337,-0.349,-0.370,P<0.05).Conclusions Bilateral knee joint strength asymmetry in hemiplegic stroke patients is negatively correlated with balance and walking ability.The difference in strength between the two sides of knee joint may be one of the clinical indicators for evaluating the motor function of stroke patients.
7.Imaging assessment of osteosarcoma chemotherapy efficacy based on multi-scale lesion attention network
Jie ZANG ; Ze-Qun SONG ; Zhen-Yu TANG ; Fang-Zhou HE ; Chao-Wei DING ; Ling-Feng WANG ; Xiao-Dong TANG
Acta Anatomica Sinica 2025;56(1):30-36
Objective To propose a high-precision deep learning-based image assessment method of osteosarcoma chemotherapy efficacy for clinical treatment,as existing methos have low accuracy of osteosarcoma assessment.Methods The low incidence of osteosarcoma led to the small scale of its imaging data and the problem of imbalance in data categories.This study combined deep learning with clinical medical information,combined the bone sarcoma generation module of BoneGAN and the scale lesion information capture module,and proposed OMLA-Net,a deep learning assessment network for chemotherapy effect of bone sarcoma based on multi-scale lesion attention network,which achieved computer-aided bone tumor assessment with integrated data augmentation and focused lesion information through pre-training and generalized loss training.Results In this study,40 cases of osteosarcoma MRI data were used as the basis for the comparison test on the generated dataset,and the OMLA-Net assessment outperformed the SOTA method Conv-LSTM-GAN in terms of the assessment effects such as accuracy and F1 scores,and the difference was statistically significant(Bootstrap statistical method P<0.05);the subsequent K-fold cross-validation ablation experiments further demonstrated the effectiveness of each module proposed by OMLA-Net.Conclusion OMLA-Net can effectively perform the impact assessment of chemotherapy effect on osteosarcoma,which provides a new idea for subsequent clinical application.
8.Clinical study on neglected perforation of glove during spinal surgery
Xiao-fang SHAO ; Bo WANG ; Shan-shan TAN ; Wen-wen HE ; Yu-feng TIAN
Journal of Regional Anatomy and Operative Surgery 2025;34(5):417-420
Objective To specify the occurrence status,distribution characteristics and risk factors of neglected perforations in surgical gloves used during spinal surgery.Methods A total of 932 surgical gloves used during spinal surgery in our hospital from October 2022 to September 2024 were selected.The occurrence and distribution location of neglected perforations were counted.Univariate and binary Logistic regression analyses were respectively conducted on the factors that might lead to neglected perforations of gloves.Results Among the 932 surgical gloves used in spinal surgery selected in this study,a total of 122 gloves(13.09%)with neglected perforations were detected,of which the proportions of neglected perforations at the index finger of the left and right hands in the gloves were the highest,accounting for 37.50%and 37.93%respectively.The results of univariate and binary Logistic regression analyses showed that grade Ⅲ or Ⅳ surgery,open surgery,combined bone grafting operation,operation time≥120 minutes,use of rotating equipment,and gloves worn by instrument nurses were risk factors for neglected perforations(P<0.05,OR>1.0),while wearing double-layer gloves was a protective factor to avoid the occurrence of neglected perforations(P<0.05,OR<1.0).Conclusion The incidence of neglected perforations in surgical gloves used during spinal surgery is relatively high,especially in the area of the glove index finger.For high-risk spinal surgeries(grade Ⅲ or Ⅳ surgery,open surgeries,combined bone grafting procedures)and requiring rotating equipment,health care workers,especially instrumental nurses,are advised to wear double-layer gloves;furthermore,a 120-minute glove change regime is recommended,in order to reduce the incidence of neglected perforation.
9.Evaluation of registration accuracy of MIM system using liver biomechanical deformation model
Xiao-fang GOU ; Xiu-xia FENG ; Song FAN
Chinese Medical Equipment Journal 2025;46(2):49-55
Objective To evaluate the registration accuracy of progressive biomechanical shrinkage set of MIM system to provide registration evaluation data support for registration demand scenarios such as treatment response feedback and dose stacking in tumor adaptive radiotherapy.Methods The CT images of a fresh pork liver with 60 gold markers in different shrinkage states at different heating time were used as the phantom images containing gold markers,and the phantom images without gold markers were obtained by replacing the pixel values at the high-density points containing the gold markers with the pixel averages of the pork liver tissue near the gold marker points.Secondly,the two types of phantom images were introduced into MIM system for registration by two methods of deformable image registration(DIR)and contour boundary-based hybrid deformable image registration(HY-DIR).Finally,the mean values of target registration errors(TRE)were cal-culated between the real gold marker points and the ones by registrating respectively all the gold marker points,23 internal points and 37 superfacial points.The Dice coefficients and Hausdorff distances were computed,and correlation and difference analyses were carried out between four groups of DIR with gold marker,HY-DIR with gold marker,DIR without gold marker and HY-DIR without gold marker.SPSS 25.0 software was used for statistical analysis.Results At 30 s time-phase,the mean values of TRE ranged from 2.14 to 2.20 mm,and the Dice coefficients were all 0.94;at 60-90 s time-phase,the mean values of TRE were from 3.02 to 5.32 mm,and the Dice coefficients were restricted between 0.95 and 0.97;at 110-200 s time-phase,the mean values of TRE were higher than 4 mm,and the Dice coefficients were from 0.93 to 0.96.The Hausdorff distance had high mean value at 30-200 s time-phase,with a minimum value of 3.85 mm and a maximum value of 17.91 mm.The mean value and standard deviation of TRE of the superfacial gold marker points were all higher than those of the internal points.In case of registration by DIR the Dice coefficients had medium-strength correlations with the TRE mean values of the internal points and all the points(0.4<r<0.6).In case of registration by HY-DIR the Dice coefficients did not correlated with the TRE mean values(r<0.2).In terms of TRE mean value there were significant difference between DIR with gold marker group and HY-DIR with gold marker group(P=0.026)and between DIR with gold marker group and DIR without gold marker group(P=0.036).Conclusion When MMI software is used for self-addaptive radiotherapy registration,satisfactory results are obtained at 30 s time-phase;at 60-90 s time-phase(volume shrinkage lower than 20%),some low registration errors occur and need artificial correction;at 100-200 s time-phase(volume shrinkage higher than 20%),high registration errors appear while the registration with gold markers be haves better than that without gold markers and DIR gains advantages over HY-DIR.[Chinese Medical Equipment Journal,2025,46(2):49-55]
10.A multicenter,randomized,control clinical trial comparing the efficacy and safety of recombinant staphylokinase and alteplase in the treatment of acute ST-segment elevation myocardial infarction
Xin-gang WANG ; Guo-feng CHANG ; Rui-ping ZHAO ; Xiao-Li GAO ; Fang-Fang FAN ; Yan-jun GONG ; Jie JIANG ; Yong HUO
Chinese Journal of Interventional Cardiology 2025;33(6):319-326
Objective To evaluate the efficacy and safety of recombinant staphylokinase in patients with acute ST-segment elevation myocardial infarction(STEMI)by a multi-center,randomized,position-controlled,parallel post-marketing clinical trial.Methods This study was a multi-center,randomized,positive drug parallel control,non-inferiority clinical trial.From July 2019 to June 2022,a total of 251 patients with STEMI were enrolled in 31 hospitals.Patients were randomly assigned to receive intravenous staphylokinase or alteplase in a ratio of 1∶1.Vascular recanalization was evaluated by clinical indicators 30 minutes,60 minutes and 120 minutes after the initiation of thrombolysis.Coronary angiography was performed 90 to 120 minutes after the initiation of thrombolysis.The proportion of infarct-related artery(IRA)with thrombolysis in myocardial infarction(TIMI)grade Ⅱ and Ⅲ,corrected TIMI frame count(CTFC)and TIMI myocardial perfusion grade(TMPG)were analyzed Major adverse cardiac events(MACE,including all-cause death,rehospitalization,reinfarction,urgent target vessel revascularization)and bleeding events were followed up at 30 days(±2 days)after thrombolysis.Results After excluding 7 subjects who did not use thrombolytic drugs,244 subjects were finally eligibled from 31 hospitals(117 in trial group and 127 in control group),and 232 subjects completed the follow-up(111 in trial group and 121 in control group).The vascular recanalization rate evaluated by clinical indicators at 120 minutes after thrombolysis was 85.6% in trial group and 83.5% in control group(P=0.657).The difference between the two groups was 2.11(95%CI-7.19-11.41).Given that the lower confidence limit of the 95%CI was greater than-12%,the non-inferiority of the vascular recanalization rate was established based on clinical judgment.Coronary angiography showed that the total patency rate of IRA(TIMIⅡ-Ⅲ)was 77.5% in trial group and 77.7% in control group(P=0.970).The difference between the two groups was-0.21(95%CI-10.95-10.54),with the lower bound of the 95%CI exceeding-12%.Therefore,the non-inferiority of the TIMI blood flow grade was confirmed,indicating that the total patency rate of IRA in the trial group was not inferior to that in the control group.The CTFC was(32.7±17.6)frames in trial group and(37.6±16.6)frames in control group,with no statistically significant difference between the two groups(P=0.054).The difference between the two groups was-4.9(95%CI-10.0-0.1).As the lower limit of the 95%CI exceeded-12%,the noninferiority of CTFC was successfully demonstrated.The proportions of TMPG 0-Ⅲ were 20.7%,6.3%,2.7%and 69.4%in trial group,and 22.3%,4.1%,6.6% and 66.9% in control group,respectively.There was no significant difference in TIMI myocardial perfusion grade between the two groups(P=0.086).The incidence of MACE was 7.7% in trial group and 7.1% in control group within 30 days after the initiation of thrombolysis,and there was no significant difference between the two groups(P=0.857).Further analysis showed that there was no significant difference in cardiovascular mortality(3.4% vs.4.7%,P=0.751).All 244 subjects were included in the safety analysis set.There was no significant difference in the total incidence of bleeding events between the two groups(22.2% vs.15.0%,P=0.144).There was no significant difference in the incidence of major bleeding(1.7% vs.0.8%,P=0.609).Conclusions Recombinant staphylokinase is simple to use and has a rapid onset of action.The efficacy and safety of recombinant staphylokinase are not inferior to alteplase in the treatment of acute STEMI.

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