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.

AIM To evaluate the quality of Tibetan medicine"Sangdi"based on HPLC fingerprints combined with chemometrics.METHODS The analysis was performed on a 30 ℃ thermostatic Welch Ultimate AQ-C18 column(250 mm × 4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2％phosphoric acid flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 245 nm,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were performed,the contents of gentiopicroside,sweroside,mangiferin,isoorientin,8-hydroxy-1,3,5-trimethoxyxanthone(R2)and 1,8-dihydroxy-3,7-dimethoxyxanthone(R3)were determined.RESULTS There were 18 common peaks in the fingerprints for 15 batches of samples with the similarities of more than 0.90.Six constituents showed good linear relationships within their own ranges(R 2 ≥ 0.999 2),whose average recoveries were 96.93％-103.58％with the RSDs of 0.82％-2.9％.Various batches of samples were clustered into 2 categories,4 principal components demonstrated the accumulative variance contribution rate of 86.404％,mangiferin,gentiopicroside and isoorientin were taken as quality difference markers.CONCLUSION This stable,reliable and reproducibe method can provide a reference for the comprehensive quality evaluation of"Sangdi".

AIM To evaluate the quality of Tibetan medicine"Sangdi"based on HPLC fingerprints combined with chemometrics.METHODS The analysis was performed on a 30 ℃ thermostatic Welch Ultimate AQ-C18 column(250 mm × 4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2％phosphoric acid flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 245 nm,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were performed,the contents of gentiopicroside,sweroside,mangiferin,isoorientin,8-hydroxy-1,3,5-trimethoxyxanthone(R2)and 1,8-dihydroxy-3,7-dimethoxyxanthone(R3)were determined.RESULTS There were 18 common peaks in the fingerprints for 15 batches of samples with the similarities of more than 0.90.Six constituents showed good linear relationships within their own ranges(R 2 ≥ 0.999 2),whose average recoveries were 96.93％-103.58％with the RSDs of 0.82％-2.9％.Various batches of samples were clustered into 2 categories,4 principal components demonstrated the accumulative variance contribution rate of 86.404％,mangiferin,gentiopicroside and isoorientin were taken as quality difference markers.CONCLUSION This stable,reliable and reproducibe method can provide a reference for the comprehensive quality evaluation of"Sangdi".

Objective:To explore the correlation between palm temperature,disease activity,and traditional chinese medicine syndrome types in patients with rheumatoid arthritis(RA).Methods:80 RA patients(RA group)who were admitted to our hospital from April 2022 to June 2024 were selected,they were divided into high group(DAS28 score＞5.1 score)and low to moderate group(2.6 score ≤ DAS28 score≤5.1 score)according to the 28 joint disease activity scores(DAS28).70 healthy volunteers who underwent physical examinations during the same period(control group)were selected.The palm temperature,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),and DAS28 scores between the control group and RA group were compared.The palm temperature,ESR,and CRP levels between low to moderate group and high group were compared.The correlation between palm temperature and disease activity,ESR,and CRP levels in RA patients was analyzed by Pearson correlation.The distribution of traditional chinese medicine syndrome types in RA patients was observed,the palm temperature,ESR,and CRP levels of RA patients with different traditional chinese medicine syndrome types were compared.Results:The palm temperature,ESR,CRP levels,and DAS28 score in the RA group were higher than those in the control group(P＜0.05).The palm temperature,ESR,and CRP levels in the high group were higher than those in the low to moderate group(P＜0.05).Pearson correlation analysis results showed that,the palm temperature of RA patients was positively correlated with DAS28 score,ESR,and CRP levels(P＜0.05).Among 80 RA patients,there were 17 cases(21.25％)of liver and kidney deficiency syndrome,23 cases(29.02％)of cold and dampness obstruction syndrome,14 cases(17.86％)of qi and blood deficiency syndrome,17 cases(21.47％)of damp heat obstruction syndrome,and 9 cases(11.52％)of phlegm and blood stasis obstruction syndrome.The palm temperature,ESR,and CRP levels of patients with Qi and blood deficiency syndrome,liver and kidney deficiency syndrome,and phlegm and blood stasis obstruction syndrome increased in sequence and were higher than those of patients with damp heat obstruction syndrome and cold and dampness obstruction syndrome(P＜0.05).There was no statistical difference in palm temperature,ESR,and CRP levels between the groups of damp heat obstruction syndrome and cold and dampness obstruction syndrome(P＞0.05).Conclusion:There is a certain correlation between the palm temperature and disease activity and traditional chinese medicine syndrome types of RA patients.Regular observation of palm temperature,ESR,CRP levels,and DAS28 score is helpful for assessing the condition of RA patients.

Objective:To explore the therapeutic effect of Banxia Baizhu Tianma Decoction on phlegm-dampness-blocking cervical vertigo and its influence on neck hemodynamics.Methods:96 patients with phlegm-dampness block type cervical vertigo admitted to our hospital from January 2022 to January 2024 were divided into control group and observation group,48 cases in each group.The control group was treated with conventional Western medicine,and the observation group was treated with Banxia Baizhu Tianma Decoction.Both groups were treated for 4 weeks and followed up for 6 months.The reduction time and disappearance time of vertigo were recorded.The score of cervical vertigo Symptom and Function Assessment Scale(ESCV)was performed before treatment and 1 day after treatment.The average blood flow level of basilar artery,right vertebral artery and left vertebral artery was detected,and the total clinical effective rate,recurrence rate and adverse reaction rate of the two groups were compared.Results:The reduction time and disappearance time of vertigo in the observation group were shorter than those in the control group(P＜0.05).Post-treatment,the ESCV score of both groups was higher than that before treatment;compared with the control group,the ESCV score of the observation group was higher post-treatment(P＜0.05).The total clinical effective rate of observation group was higher than that of control group,and the recurrence rate was lower than that of control group(P＜0.05).The hemodynamic index were higher after treatment than in the control group(P＜0.05).There was no difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Banxia Baizhu Tianma Decoction has certain curative effect on phlegm-dampness block type cervical vertigo,can effectively relieve vertigo symptoms,reduce recurrence,improve neck hemodynamics,and is safe,worthy of popularization and application.

Objective To investigate the comparative neuroprotective effects of human umbilical cord mesenchymal stem cells(hUC-MSCs-Exos)administered via different routes on hypoxic ischemic brain damage(HIBD)in neonatal mice.Methods Healthy one-week-old SPF-grade BALB/c mice were randomly divided into 4 groups:sham operation group(n=6),model group(n=6),exosome group 1(n=8),exosome group 2(n=8).HIBD was induced using the Rice-Vannucci method.Exosome group 1 and Exosome group 2 were intraperitoneal injection/intranasal drip of phosphate buffer(PBS)100 μl containing 10 μl exosomes within 24 h after successful modeling,respectively.Sham operation and model groups were intraperitoneal injection of PBS 100 μl.On the 7th day after the intervention,neuromotor function was assessed using the horizontal grid test and pole climbing test.On the 2nd day after the evaluation,all mice were killed and their brains were removed by decapitation.HE staining was used to observe the pathological injury of brain tissue,toluidine blue staining was used to observe the survival of neurons in cerebral cortex,and TUNEL staining was used to observe the apoptosis of cerebral cortex cells.Results Compared with sham operation group,model group,exosome group 1 and exosome group 2 exhibited increased hind limb drops in horizontal grid test and climbing scores(P<0.05).No significant difference was found in model group,exosome group 1 and exosome group 2 in these measures(P<0.05).Significant pathology was observed in model group,exosome group 1 and exosome group 2 compared to sham operation group(P<0.05),with significantly reduced damage in exosome group 1 and exosome group 2 compared to model group(P<0.05).Compared with sham operation group,Nissl body count was lower in model group and exosome group 1 and exosome group 2,with a higher count in exosome group 2 compared to exosome group 1(P<0.05).Compared with sham operation group,apoptotic cells were higher in model group and exosome group 1 and exosome group 2,with a significant reduction in exosome group 1 and exosome group 2 compared to model group,and the lowest in exosome group 2(P<0.05).Conclusions hUC-MSCs-Exos can improve the neuronal motor function,promote neuron repair and inhibit apoptosis in HIBD mice.Intranasal administration of hUC-MSCs-Exos is more effective than intraperitoneal administration for reducing neuronal apoptosis in HIBP neonatal mice,offering a convenient and rapid method suitable for clinical application.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

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.

Developmental neurotoxicity(DNT)has been recognized as an important aspect of risk assessment.However,traditional in vivo tests are limited by an increasing need to assess the risk of numerous industrial chemicals.The DNT in-vitro testing battery(DNT IVB)has emerged that can reduce animal use with potential cost-efficiencies.In this article,the progress and targets of DNT IVB are explored in general and the DNT in vitro testing methods and alternative in vitro models in particular.The appli-cability of DNT in vitro testing data based on integrated approach to testing and assessment(IATA)is evaluated.In conclusion,with the development of high-throughput screening and human-derived cell models,DNT IVB can better align with priority testing requirements in modern DNT risk assessment frameworks and deliver validated in vitro alternatives for regulatory compliance.

Icaritin(ICT)is an 8-isopentenylflavonoid,which is the main effective component of the tra-ditional Chinese medicine Epimedium.Previously,we found that Icaritin inhibits the growth of glioblasto-ma(GBM)cells.Herein we aim to study the in vivo anti-GBM effectiveness of Icaritin and explore its mechanism.The results of MTT assay,flow cytometry,comet assay and cellular immunofluorescence as-say in vitro showed that ICT inhibited the proliferation of four kinds of GBM cells,U87,U251,U118 and A172,induced early apoptosis(P＜0.001)and late apoptosis(P＜0.05)in U87 cells,induced DNA damage in U87 cells,and blocked the growth of U87 cells at the G0/G1 phase(P＜0.0001)in a concen-tration-time-dependent manner.In vivo subcutaneous tumor transplantation tumor experiments showed that feeding 200 mg/kg(P＜0.01)and 400 mg/kg(P＜0.001)ICT had a significant inhibitory effect on the growth of GBM subcutaneous tumors,and had no significant toxic effects on heart,liver,spleen,lung and kidney tissues.The results of network pharmacological analysis,molecular docking and cellular thermodynamic experiments showed that there were 26 possible target proteins between ICT and GBM,a-mong which the expression of p53 in GBM tissues was significantly(P＜0.001)higher than in normal tis-sues,and the binding energy of ICT and p53 was lower;cellular thermodynamic experiments verified that ICT significantly enriched the level of p53 in the living cells of GBM,which indicated that ICT could tar-get p53.The expression of key proteins in the DNA damage repair and apoptosis-associated FOXO signa-ling pathway was detected by ICT.The results showed that the expression of ATR(P＜0.01),P53(P＜0.001),P21(P＜0.05)and γ-H2AX(P＜0.05)was up-regulated,whereas the expression of Cyc-lin E1(P＜0.01),E2F1(P＜0.05),CDK2(P＜0.01),Rb(P＜0.001),p-Rb(P＜0.0001)and WRN(P＜0.0001)expression were down-regulated.There was no significant change in the expres-sion of FOXO 1 in the FOXO pathway or a significant down-regulation of its phosphorylation level.This study demonstrated that ICT could effectively inhibit the growth of GBM cells in vivo.It targets p53 to regulate the DNA damage repair pathway and FOXO signaling pathway to induce GBM cell cycle arrest and apoptosis.