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.

Objective: Spinal stenosis and degenerative spinal disorders are increasingly prevalent and have a substantial impact on quality of life. Surgical decompression, performed using either open microscopic or endoscopic approaches, remains a cornerstone of management for these conditions. This study examines evolving trends in single-level lumbar spinal decompression procedures performed at a tertiary academic hospital in Singapore. Methods: A retrospective observational study was conducted involving 588 patients who underwent single-level spinal decompression between 2021 and 2024, including endoscopic spine surgery (ESS; n=364) and microdecompression (n=224). Primary outcome measures were changes in 36-Item Short Form Health Survey (SF-36) and visual analogue scale (VAS) scores at 3 months, 6 months, and 2 years postoperatively. Secondary outcomes included length of hospital stay, reoperation rates, and operative time. Patient demographics, spinal level and pathology characteristics, surgical techniques, and postoperative outcomes were analyzed. Difference-in-differences (DID) analysis was used to compare outcomes between the 2 groups. Results: Both groups demonstrated significant postoperative improvements in SF-36 and VAS scores. At 2 years, Short Form Health Survey physical function (SFPF) scores improved in the endoscopic group (mean difference [MD], 18.6; standard deviation [SD], 21.7; p=0.064) and in the open microscopic group (MD, 36.7; SD, 20.9; p=0.007), with a non-significant DID of -18.1 (p=0.155). No DID comparisons across SF-36 domains reached statistical significance. Mean operative time for endoscopic procedures decreased from 249 minutes in 2022 to 145 minutes in 2024, reflecting a procedural learning curve. Surgeons with higher endoscopic caseloads exhibited greater improvements in functional outcomes. Conclusion Both endoscopic and open microscopic decompression achieve comparable short- and long-term clinical outcomes. ESS provides similar effectiveness while being associated with shorter recovery periods and reduced hospital stay. Further research is warranted to identify factors contributing to incomplete symptom resolution or the need for revision surgery.

Background: Patients with coarctation of the aorta (CoA) and an interrupted aortic arch (IAA) may present with small mitral valves (MVs) and a reduced left ventricular (LV) volume. Biventricular repair (BVR) in these patients is dependent on adequate size of the left cardiac structures.Purpose: This study evaluated the impact of the hemodynamic characteristics of atrial septal defects (ASDs) on MV growth following surgical repair. Methods: We retrospectively reviewed the data of patients diagnosed with CoA or IAA between 2007 and 2024. The z score for MV size measured 6 months postoperatively (Z2) was compared with the preoperative MV size (Z1). The factors associated with MV growth were also studied. Results: A total of 161 patients with CoA or IAA were included. Transthoracic echocardiography was used to assess the MV and LV dimensions preoperatively and 6 months postoperatively. Of the cohort, 155 (96.3%) underwent initial BVR and 6 underwent single-ventricle palliation. MV z scores significantly increased following BVR (mean change: +0.45±1.35; P<0.001) but decreased after single-ventricle repair (-0.56±0.49, P=0.04). Multivariate analysis identified the initial MV z score and ASD pressure gradient as independent predictors of MV growth (R2=0.39). Conclusion Annular growth of the MV was not observed in patients who underwent single-ventricle palliation. In contrast, among patients who achieved BVR, those with a small preoperative MV annulus and low ASD pressure gradient demonstrated subsequent catch-up MV growth, suggesting that adequate left-sided preload is essential for MV development.

Aerosol-assisted plasma amplification laser-induced breakdown spectroscopy(LIBS)was employed for phosphorus detection in water.To address the multivariate coupling effects in LIBS and nebulization sampling system,an orthogonal experiment was employed to systematically optimize the key experimental parameters.Using the orthogonal experimental design,the parametric effects of laser energy(output voltage),signal acquisition delay,liquid velocity,and gas velocity on the signal to background ratio(SBR)of P I 213.618 nm were evaluated,and the optimal conditions were achieved,including laser energy of 86 mJ,delay time of 3 μs,gas velocity of 1.05 mL/min,and liquid velocity of 60 μL/min,which were in agreement with the control-variable optimization results.Moreover,the SBR response trends at P I 213.618 nm with all experimental parameters was strong in consistency with control-variable optimization results,which demonstrated the validity of the orthogonal array experimental design.This study established an efficient and accurate parameter optimization methodology for complex LIBS systems,significantly advancing the application of LIBS in environmental monitoring.

BACKGROUND:During the treatment of posterolateral tibial plateau fractures through the fibular head approach,the gap between the fibular head and the lateral plateau cannot accommodate the posterior placement of a plate for all patients.OBJECTIVE:To analyze,via finite element analysis,the differences in fixation strength resulting from varying the angles and quantities of horizontal arm variable angle screws in the plate during the treatment of posterolateral tibial plateau fractures through the fibular head approach.METHODS:A finite element model was established based on CT images of the knee to ankle joints of a 30-year-old healthy adult male volunteer.The models were divided into two categories:posteriorly placed group and non-posteriorly placed group based on whether the lateral locking compression plate was posteriorly placed.The posteriorly placed group was further subdivided into groups A-D based on the offset angle of the two variable angle screws(0°,5°,10°,and 15°).The non-posteriorly placed group was subdivided into groups E and F based on offset angles(0° and 15°).Finite element analysis was used to evaluate the von Mises stress distribution,maximum von Mises stress,and compressive displacement under loads of 250,500,and 750 N,exploring the mechanical differences between the groups.RESULTS AND CONCLUSION:(1)Finite element analysis results showed that under a 750 N load,the maximum compressive displacement trend of the internal fixation device was D＜B=C=F＜A＜E.The trend for maximum von Mises stress was B＜C＜A＜D＜F＜E.The trend for maximum compressive displacement on the bone was C=D＜B＜A＜F＜E,and for maximum von Mises stress,it was B＜C＜A＜F＜D＜E.The displacement and stress trends for the six models were similar under loads ranging from 250 N to 750 N.(2)These results suggest that for posterolateral tibial plateau fractures fixed through the fibular head approach,posterior placement of the plate should aim to accommodate two screws.If only one screw can be fixed during surgery,variable angle screws should be offset in the range of 0-15° to increase the probability of securing two screws.

Objective:To investigate the effects and underlying mechanism of ionizing radiation on the adipogenic of mesenchymal stem cells(MSCs).Methods:Mouse MSCs were cultured in vitro and treated with 2 Gy and 6 Gy radiation with 60Co,and the radiation dose rate was 0.98 Gy/min.Bulk RNA-seq was performed on control and irradiated MSCs.The changes of adipogenic differentiation and oxidative stress pathways of MSC were revealed by bioinformatics analysis.Oil Red O staining was used to detect the adipogenic differentiation ability of MSCs in vitro,and real-time fluorescence quantitative PCR(qPCR)was used to detect the expression differences of key regulatory factors Cebpa,Lpl and Pparg after radiation treatment.At the same time,qPCR and Western blot were used to detect the effect of inhibition of Nrf2,a key factor of antioxidant stress pathway,on the expression of key regulatory factors of adipogenesis.Moreover,the species conservation of the irradiation response of human bone marrow MSCs and mouse MSC was determined by qPCR.Results:Bulk RNA-seq suggested that ionizing radiation promotes adipogenic differentiation of MSCs and up-regulation of oxidative stress-related genes and pathways.The results of Oil Red O staining and qPCR showed that ionizing radiation promoted the adipogenesis of MSCs,with high expression of Cebpa,Lpl and Pparg,as well as oxidative stress-related gene Nrf2.Nrf2 pathway inhibitors could further enhance the adipogenesis of MSCs in bone marrow after radiation.Notably,the similar regulation of oxidative pathways and enhanced adipogenesis post irradiation were observed in human bone marrow MSCs.In addition,irradiation exposure led to up-regulated mRNA expression of interleukin-6 and down-regulated mRNA expression of colony stimulating factor 2 in human bone marrow MSCs.Conclusion:Ionizing radiation promotes adipogenesis of MSCs in mice,and oxidative stress pathway participates in this effect,blocking Nrf2 further promotes the adipogenesis of MSCs.Additionally,irradiation activates oxidative pathways and promotes adipogenic differentiation of human bone marrow MSCs.

Objective:To establish an in vitro cell model simulating acute graft-versus-host disease(aGVHD)bone marrow microenvironment injury with the advantage of mouse serum of aGVHD model and explore the effect of serum of aGVHD mouse on the adipogenic differentiation ability of mesenchymal stem cells(MSCs).Methods:The 6-8-week-old C57BL/6N female mice and BALB/c female mice were used as the donor and recipient mice of the aGVHD model,respectively.Bone marrow transplantation(BMT)mouse model(n=20)was established by being injected with bone marrow cells(1 × 10'per mouse)from donor mice within 4-6 hours after receiving a lethal dose(8.0 Gy,72.76 cGy/min)of y ray general irradiation.A mouse model of aGVHD(n=20)was established by infusing a total of 0.4 ml of a mixture of donor mouse-derived bone marrow cells(1 × 107 per mouse)and spleen lymphocytes(2 × 106 per mouse).The blood was removed from the eyeballs and the mouse serum was aspirated on the 7th day after modeling.Bone marrow-derived MSCs were isolated from 1-week-old C57BL/6N male mice and incubated with 2％,5％and 10％BMT mouse serum and aGVHD mouse serum in the medium,respectively.The effect of serum in the two groups on the in vitro adipogenic differentiation ability of mouse MSCs was detected by Oil Red O staining.The expression levels of related proteins PPARy and CEBPα were detected by Western blot.The expression differences of key adipogenic transcription factors including PPARy,CEBPα,FABP4 and LPL were determined by real-time quantitative PCR(RT-qPCR).Results:An in vitro cell model simulating the damage of bone marrow microenvironment in mice with aGVHD was successfully established.Oil Red O staining showed that the number of orange-red fatty droplets was significantly reduced and the adipogenic differentiation ability of MSC was impaired at aGVHD serum concentration of 10％compared with BMT serum.Western blot experiments showed that adipogenesis-related proteins PPARy and CEBPα expressed in MSCs were down-regulated.Further RT-qPCR assay showed that the production of PPARy,CEBPα,FABP4 and LPL,the key transcription factors for adipogenic differentiation of MSC,were significantly reduced.Conclusion:The adipogenic differentiation capacity of MSCs is inhibited by aGVHD mouse serum.

Construct Validity and Reliability of the Malay Version of Rosenberg Self Esteem Scale (RSES) among youth in Southern Malaysia: A Confirmatory Factor Analysis IntroductionThe Rosenberg Self-Esteem Scale (RSES) is widely used to measure self-esteem among adults and youth. This study aims to determine the construct validity and reliability of the Rosenberg Self-Esteem Scale Malay version (RSES-M) among Malaysian youth using Confirmatory Factor Analysis (CFA).MethodologyWe administered the Malay-language RSES to 378 Form Four students in the Kota Tinggi District, selected through multistage sampling. The construct validity of RSES-M was assessed using confirmatory factor analysis (CFA), while internal consistency was measured using Cronbach alpha. AMOS version 26 and SPSS version 20 were used for statistical analysis. We compared three measurement models of the RSES-M for the best relative fit: one uni-dimensional model and two different two-domain models (with different items assigned to each domain for each model).ResultsThe findings indicate that the best model for the RSES-M was a two-domain model, with domain one representing positive self-esteem and domain two representing negative self-esteem. The item “I wish I could respect myself more” demonstrated a strong fit within the CFA model when included under the positive domain of self-esteem (Model 3) compared to negative domain ((Model 2) (Chi-Square/degree of freedom (df) = 3.341, goodness of fit (GFI) = 0.967, Comparative Fit Index (CFI) = 0.905, Incremental Fit Index (IFI) = 0.906, and the Root Mean Squared Error of Approximation (RMSEA) = 0.079 and substantial reliability (Cronbach's alpha for domain one = 0.765, and domain two = 0.648). This finding diverges from the original RSES developed by Morris Rosenberg in 1965, which conceptualised the RSES as a unidimensional construct, and other studies that categorised the item "I wish I could respect myself more" under the negative self-esteem domain.

Objective:To explore the therapeutic efficacy and prognostic factors of combined rituximab and intensive chemotherapy for sporadic adult Burkitt lymphoma (BL) .Methods:This retrospective study examined the clinical and survival data of 30 patients newly diagnosed with BL between July 2011 and February 2023 at the Blood Diseases Hospital. Kaplan-Meier method was used for survival analysis, and the log-rank test was used for univariate analysis of prognostic factors.Results:The median age of the 30 patients was 43 years (24 - 66 years), and the male to female ratio was 3: 2. Extranodal invasion was present in 80% of the patients, with involvement of the bone marrow in 53.3% and central nervous system in 10.0%. The Ann Arbor stage was Ⅲ and Ⅳ in 86.7%. According to the number of Burkitt Lymphoma International Prognostic Index (BL-IPI) risk factors, patients were classified as low risk (0) in 20.0%, intermediate risk (1) in 43.3%, and high risk (≥2) in 36.7%. All patients were treated with an induction regimen of rituximab combined with intensive chemotherapy, with objective and complete response rates of 80.0% and 76.7%, respectively. The median follow-up was 49 months (6-153 months), and the 5-year progression-free survival (PFS) and overall survival (OS) rates were both (76.7±7.7) %. All patients with limited stage ( n=4) achieved continuous complete remission (CCR). Patients who had high risk, advanced stage sensitive to induction therapy ( n=10) sequentially received first-line autologous hematopoietic stem cell transplantation (auto-HSCT) as consolidation therapy; 9 patients achieved CCR, whereas 1 patient with central nervous system invasion developed early disease progression and died. The BL-IPI low, intermediate, and high risk groups had respective 5-year PFS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % ( P=0.0069) and OS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % ( P=0.0075). The main adverse effects of induction therapy were myelosuppression and secondary infections, which were effectively managed by appropriate symptomatic treatment. Univariate analysis demonstrated that worse PFS was associated with BL-IPI score ≥2 ( HR=4.90, 95% CI 1.02-23.45, P=0.0329) ; extranodal invasion at ≥2 sites ( HR=12.62, 95% CI 2.59-61.62, P=0.0021) ; and failure to achieve first complete response (CR1) after induction therapy ( HR=31.86, 95% CI 4.19-242.20, P<0.0001) . Conclusions:Intensive immunochemotherapy regimens were effective and well-tolerated by adult patients with highly aggressive BL. Treatment efficacy was ideal in patients with limited-stage disease, whereas prognosis was unsatisfactory in patients with high-risk BL-IPI. Sequential first-line auto-HSCT consolidation therapy may further improve outcomes in patients with high-risk advanced-stage disease who are sensitive to induction therapy. BL-IPI score ≥2, extranodal invasion at ≥2 sites, and failure to achieve CR1 after induction therapy were adverse prognostic factors in adult patients with BL.