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.A qualitative study of parent-child interactions in infants and toddlers with language delays and an exploration of their application in home intervention
Siwei MA ; Sha LAI ; Chunfang A ; Yuhan LIU ; Binting YANG
Journal of Audiology and Speech Pathology 2025;33(2):119-123
Objective To identify specific behaviors detrimental to language development in parent-child inter-actions among Mandarin-speaking infants and toddlers with language delays,and to provide a foundation for develo-ping parent-involved early intervention programs that enhance language acquisition.Methods A qualitative research design was used,employing interaction analysis and categorical analysis methods.Observations from 30 parent-child interaction videos involving children with delayed language development were analyzed to identify common detrimen-tal behaviors(coding).The validity of the qualitative findings was tested by analyzing 108 parent-child where low-quality parental interactions were identified and provided with five rounds of constructive feedback.Results Two major categories of detrimental behaviors with three aspects and a total of 10 issues were identified:5 issues related to parental interaction skills,3 issues related to mutual influences between parent and child,and 2 issues related to the interaction environment.After 5 rounds of feedback,detrimental behaviors in the 108 parent-child pairs im-proved significantly,with 8 behaviors met the 80%stability standard.Conclusion The study identified and catego-rized behaviors in parent-child interactions that hinder language development in children with language delays.Video-based behavior analysis and feedback can enhance parental interaction skills and create a conductive environ-ment for early language development.
3.A qualitative study of parent-child interactions in infants and toddlers with language delays and an exploration of their application in home intervention
Siwei MA ; Sha LAI ; Chunfang A ; Yuhan LIU ; Binting YANG
Journal of Audiology and Speech Pathology 2025;33(2):119-123
Objective To identify specific behaviors detrimental to language development in parent-child inter-actions among Mandarin-speaking infants and toddlers with language delays,and to provide a foundation for develo-ping parent-involved early intervention programs that enhance language acquisition.Methods A qualitative research design was used,employing interaction analysis and categorical analysis methods.Observations from 30 parent-child interaction videos involving children with delayed language development were analyzed to identify common detrimen-tal behaviors(coding).The validity of the qualitative findings was tested by analyzing 108 parent-child where low-quality parental interactions were identified and provided with five rounds of constructive feedback.Results Two major categories of detrimental behaviors with three aspects and a total of 10 issues were identified:5 issues related to parental interaction skills,3 issues related to mutual influences between parent and child,and 2 issues related to the interaction environment.After 5 rounds of feedback,detrimental behaviors in the 108 parent-child pairs im-proved significantly,with 8 behaviors met the 80%stability standard.Conclusion The study identified and catego-rized behaviors in parent-child interactions that hinder language development in children with language delays.Video-based behavior analysis and feedback can enhance parental interaction skills and create a conductive environ-ment for early language development.
4.Comparison of efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children: a multicenter, randomized, controlled clinical trial
Xing XIAO ; Shan WANG ; Huan YANG ; Hong SHU ; Yanping GUO ; Jinping CHEN ; Yao LU ; Qinfeng LI ; Yuan LIANG ; Mutong ZHAO ; Xiaoyan LUO ; Limin MIAO ; Rui XU ; Xuemei LI ; Sha LAI ; Jianhong LI ; Zhen LUO ; Lu YU ; Lu XING ; Meitan WANG ; Xiaoli LI ; Haitao XU ; Ping LI ; Hua WANG ; Lin MA
Chinese Journal of Dermatology 2025;58(5):425-430
Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.
5.Clinical and Immunological Characteristics of Elderly Onset Rheumatoid Arthritis
Zhengfang LI ; Chanyuan WU ; Mengsi MA ; Tingting LI ; Xue WU ; Xinyan MENG ; Sha ZHANG ; Lijun WU
Medical Journal of Peking Union Medical College Hospital 2025;16(1):59-64
To investigate the clinical features and peripheral blood immune cell subsets ofelderly (≥60 years old) onset rheumatoid arthritis (EORA) patients. The patients with rheumatoid arthritis (RA) who were hospitalized in the Department of Rheumatology and Immunology of the People's Hospital of Xinjiang Uygur Autonomous Region from March 2023 to December 2023 were selected as the study objects. The demographic data, clinical characteristics, extra-articular manifestations and laboratory examination results of the patients were collected. The patients were divided into EORA group and young adult (< 60 years old)onset rheumatoid arthritis (YORA) group, and the clinical features and peripheral blood immunological indexes of the two groups were compared. A total of 187 RA patients with an average age of (62.1±12.0) years were enrolled, including 89 patients in the EORA group and 98 patients in the YORA group. Compared with YORA group, EORA group had a higher proportion of male patients(39.3% Compared with YORA, EORA has higher male proportion, joint disease degree and disease activity. EORA is prone to interstitial lung disease, anemia and high inflammation, and the level of peripheral blood NK cells is higher.
6.Prognostic Significance of KMT2D Gene Mutation and Its Co-mutated Genes in Patients with Diffuse Large B-Cell Lymphoma
Mutibaier·MIJITI ; Xiaolong QI ; Renaguli·ABULAITI ; Wenxin TIAN ; Sha LIU ; Weiyuan MA ; Zengsheng WANG ; Li AN ; Min MAO ; Muhebaier·ABUDUER ; Yan LI
Cancer Research on Prevention and Treatment 2025;52(2):127-132
Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2DmutBTG2mut had poorer OS than those with KMT2Dwt BTG2mut (P=0.07) and KMT2Dwt BTG2wt (P=0.05). On the contrary, patients with KMT2Dmut CD79Bmut had better OS than those with KMT2Dmut CD79Bwt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2DmutBTG2mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.
7.Application effect of visual eye dressings in patients after bilateral strabismus surgery
Wei SONG ; Ying SHA ; Hang YIN ; Zhangfang MA
Chinese Journal of Modern Nursing 2025;31(17):2335-2337
Objective:To explore the application effect of visual eye dressings in patients after bilateral strabismus surgery.Methods:A total of 60 patients who underwent bilateral strabismus surgery in the Department of Ophthalmology of Beijing Tongren Hospital, Capital Medical University, from March to August 2024, were selected by convenience sampling. The patients were randomly divided into an observation group and a control group using a random number table method, with 30 cases in each group. After surgery, the control group was treated with conventional eye dressings, while the observation group was treated with visual eye dressings. The daily living ability, unplanned dressing changes were compared between the two groups.Results:The observation group had higher daily living ability scores and fewer unplanned dressing changes than the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The use of visual eye dressings in patients after bilateral strabismus surgery has a positive effect on maintaining daily living ability and reducing the frequency of unplanned dressing changes.
8.A prospective study on clinical monitoring of early cardiac myocardial dysfunction by conventional radiotherapy in N 2-N 3 non-small cell lung cancer with lymph node metastases
Yiying ZHU ; Hao ZHANG ; Weiwei OUYANG ; Shengfa SU ; Yinxiang HU ; Zhu MA ; Sha LI ; Qingsong LI ; Wengang YANG ; Xiaxia CHEN ; Haijie JIN ; Jie LIU ; Fuhuan LUO ; Zhourui LIU ; Bing LU
Chinese Journal of Radiation Oncology 2025;34(7):664-670
Objective:To analyze the changes and significance in clinical cardiac indicators of early cardiac myocardial dysfunction and cardiac substructure dose during conventional radiotherapy for N 2-N 3 non-small cell lung cancer (NSCLC) with mediastinal lymph node metastases. Methods:The data of 34 NSCLC patients with lymph node metastases in regions 4-8 admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to August 2023 were observed and analyzed. All patients were treated with volumetric modulated arc therapy with a prescribed dose of 60-70 Gy. Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at 6 time points: within 1 week before radiotherapy ( t0); when the cumulative radiotherapy dose reaches 20 Gy ( t20), 40 Gy ( t40), 60 Gy ( t60) during radiotherapy; within 1 week after radiotherapy ( tp); 1 month after radiotherapy( tp1). Left ventricular global longitudinal strain (LVGLS) and left atrial global longitudinal strain (LAGLS) were assessed at 4 time points: t0, t40, tp and tp1, respectively. The changes in cardiac indicators at different time points during radiotherapy and their correlation with substructure doses were analyzed using analysis of variance, linear regression analysis, and Pearson correlation. Results:The correlation between cardiac substructure dose and mean heart dose (MHD) in the study cohort in the descending order was as follows: left ventricle ( B=0.43, P<0.001), right ventricle ( B=0.37, P=0.002), left atrium ( B=0.16, P<0.001), and right atrium ( B=0.15, P=0.001). There were significant differences in the changes of LVGLS and LAGLS across different time points ( F=3.13, P=0.029; F=17.18, P<0.001). At 1 month after radiation, LAGLS was significantly decreased compared to pre-radiation levels ( P=0.009), whereas no significant difference was observed in LVGLS ( P=1.000). No significant differences were observed in the changes of cTnT and NT-proBNP across different time points (all P>0.05). Significant correlations were identified between cTnT and right ventricle mean dose at t40 ( r=0.38, P=0.025), as well as between NT-proBNP and right atrium mean dose at t60 and tp ( r=0.54, P=0.001; r=0.41, P=0.016). Conclusions:At present, there is no significant difference between the sensitive serum markers of myocardial injury and LVGLS in detecting early myocardial injury. LAGLS may hold substantial clinical value. There is uncertainty about radiation injury and repair of various cardiac substructures.
9.Diagnostic value of three-dimensional arterial spin labeling in patients with isolated vertigo due to posterior circulation ischemia
Qian LIU ; Rongchao MA ; Luna WANG ; Xuan HE ; Dujuan SHA
International Journal of Cerebrovascular Diseases 2025;33(2):93-100
Objective:To investigate the predictive value of three-dimensional arterial spin labeling (3D-ASL) for posterior circulation ischemia (PCI) and posterior circulation stroke (PCS) in patients with isolated vertigo.Methods:Patients with isolated vertigo underwent 3D-ASL imaging at Drum Tower Hospital Affiliated to Nanjing University School of Medicine from January 1, 2022 to December 31, 2024 were included retrospectively. According to the imaging findings, the patients with isolated vertigo were divided into PCI group and non-PCI group. The PCI group was further divided into PCS group and non-PCS group. The baseline clinical data and laboratory examination data were collected. Cerebral blood flow (CBF) in different brain regions of the posterior circulation was obtained through 3D-ASL related parameters to evaluate the posterior circulation perfusion, including CBF at two post-labeling delay times (PLD) (1.5 s and 2.5 s), delayed perfusion CBF (ΔCBF), multisequence PLD (Multi-PLD) CBF, and CBF under arterial transit time (ATT). Multivariate logistic regression analysis was used to determine the association of different CBF values with PCI and PCS in patients with isolated vertigo. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of different CBF values for PCI and PCS. Results:A total of 81 patients with isolated vertigo were included, aged 63.0±12.1 years, 44 were males (54.3%); 58 (71.6%) had PCI and 27 (25.9%) had PCS. Multivariate logistic regression analysis showed that PLD 1.5 s-CBF (odds ratio [ OR] 1.372, 95% confidence interval [ CI] 1.169-1.611; P<0.001), ΔCBF ( OR 1.197, 95% CI 1.072-1.336; P=0.001), and Multi-PLD-CBF ( OR 2.099, 95% CI 1.257-3.504; P=0.005) were the independent predictive factors of PCI. ROC curve analysis showed that the area under the curve for predicting PCI using the above three parameters alone and in combination were 0.962 (95% CI 0.915-1.000), 0.683 (95% CI 0.543-0.823), 0.944 (95% CI 0.985-1.000), and 0.999 (95% CI 0.997-1.000), respectively. Multivariate logistic regression analysis showed that the PLD 1.5 s-CBF ( OR 1.246, 95% CI 1.030-2.089; P=0.002), ΔCBF ( OR 1.153, 95% CI 1.038-1.281; P=0.008), and multi-PLD-CBF ( OR 1.388, 95% CI 1.219-1.689; P=0.001) in cerebellar region were the independent predictors of PCS. ROC curve analysis showed that the area under the curve for predicting PCS using the above three parameters alone and in combination were 0.956 (95% CI 0.911-1.00), 0.802 (95% CI 0.685-0.920), 0.972 (95% CI 0.923-1.000), and 0.977 (95% CI 0.937-1.00), respectively. Conclusion:3D-ASL can predict PCI and PCS early, and combining multiple parameters can improve the predictive ability for PCI and PCS.

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