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.

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.

Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depres-sion model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to as-sess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin im-proved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially ex-pressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inosi-tol phosphate metabolism.Conclusion The antide-pressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.

OBJECTIVE To conduct the epidemiological survey for 4 patients with carbapenem-resistant Klebsiella pneumoniae(CRAB)that gathered to emerge in intensive care unit(ICU)within a short period so as to find out the sources of suspected CRAB.METHODS The clinical data and epidemiological history of the 4 patients with hospital-associated infection with CRAB who were treated in Shandong Provincial Hospital Affiliated to Shandong First Medical University from Mar.31,2023 to Apr.7,2023 were retrospectively analyzed.The whole genome second-generation sequencing was carried out for the CRAB strains isolated from the patients and their surround-ings,and the sources of the CRAB strains were traced by means of the whole genome sequencing.RESULTS The result of the epidemiological survey showed that the case 1,2,3 and 4 were close in spatial position and had the similar drug resistance spectrum,and there might be cross infection.With the combination of the result of genome analysis,it was found that the strain from the case 1 was brought from the community and was the evolutionary branch different from other CRAB strains causing nosocomial infection;the strains from the case 2,3 and 4 had the close original sources with the CRAB strains from surroundings.CONCLUSIONS The CRAB strain from the case 1 is brought from community,which differs in the evolution branch with the strains from the cases of hospi-tal-associated CRAB infection.The transmission of CRAB leading to the incident of suspected hospital-associated infection outbreak is multiple sources.It is an effective measure to early identify the outbreak of hospital-associated infection and take targeted prevention measures so as to control the outbreak of hospital-associated infection.

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 analyze the associated factors and cumulative effects of cardiometabolic multimorbidity (CMM) among residents in southern Xinjiang.Methods:A stratified random cluster sampling method was used to conduct questionnaire surveys, physical examinations and laboratory tests among the personnel of the 51st Brigade, 3rd Division, Xinjiang, in 2016. The multivariate logistic regression, multivariate linear regression, restricted cubic spline, and network analysis methods were used to study the association of lifestyle (smoking, alcohol consumption and physical activity), socioeconomic (occupation, education and marital status) and clinical factors (waist circumference, body mass index and family history) with CMM.Results:A total of 12 773 study subjects were included. The prevalence of cardiovascular metabolic diseases among residents in southern Xinjiang was 52.49%. Specifically, the prevalence rates of dyslipidemia, hypertension, coronary heart disease, diabetes, and stroke were 31.14%, 29.95%, 6.78%, 6.26%, and 2.47%, respectively, and the prevalence of CMM was 19.06%. Multivariate logistic regression analysis revealed that the associations between clinical and socioeconomic factors and CMM significantly increased with higher scores. Specifically, the OR rose from 1.75 (clinical factors) and 1.07 (socioeconomic factors) on a score of 1 to 4.41 and 1.93 on a score of 3, respectively. The association between lifestyle factors and CMM was only observed at higher scores ( OR=1.26, 95% CI:1.07~1.62). The trend test using the scores of each group as continuous variables in the model showed that the risk of disease increased with the accumulation of clinical, socioeconomic and lifestyle factors (all P<0.05). Restricted cubic spline analysis demonstrated a non-linear relationship between the total number of associated factors and CMM ( Poverall<0.05 and Pnon-linear<0.05). Network analysis identified hypertension (strength=0.42) as the “core node” among the five diseases. When analyzing the three types of influencing factors, hypertension (strength=0.68), dyslipidemia (strength=0.47), coronary heart disease (strength=0.37), and clinical factors (strength=0.53) emerged as “core nodes”. In the network of nine associated factors, abnormal waist circumference and BMI (strength=0.90 and 0.84) were identified as “key factors”, while hypertension (strength=0.68) and dyslipidemia (strength=0.52) were identified as “key diseases”. Conclusion:The prevalence of CMM among residents in southern Xinjiang is high, and there is a cumulative effect of multiple factors. Hypertension and dyslipidemia are key diseases in the multimorbidity network, while abnormal BMI and waist circumference are key associated factors.

Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depres-sion model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to as-sess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin im-proved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially ex-pressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inosi-tol phosphate metabolism.Conclusion The antide-pressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.

Objective To analyze the relationship between the expression levels of post-meiosis isolated protein 2(PMS-2)and p-glycoprotein(PGP)in gastric cancer tissues and clinicopathological characteristics,prognosis and immune function.Methods The clinical data of 100 patients with gastric cancer who visited the hospital from May 2018 to February 2022 were selected for retrospective analysis.All patients received radical surgical treatment.The expression levels of PGP and PMS-2 proteins in adjacent tissues and cancer tissues were determined by immunohistochemistry,and the correlations between the expression of PGP and PMS-2 proteins in cancer tissues and the clinicopathological characteristics and immune function of patients with gastric cancer were analyzed.The patients were followed up for 3 years after the operation to analyze the influencing factors of prognosis in patients with gastric cancer,as well as the correlation between the protein expressions of PGP and PMS-2 in cancer tissues and prognosis.Results The positive expression rates of PGP and PMS-2 proteins in cancer tissues were higher than those in adjacent tissues(P<0.05).Positive expression of PMS-2 and PGP protein was significantly associated with advanced clinical stage(stage Ⅲ),presence of lymph node metastasis,and poorer tumor differentiation(P<0.05).However,their expression showed no significant correlation with age,gender,Lauren classification,vascular invasion,or tumor diameter(P>0.05).The preoperative CD4+/CD8+levels of gastric cancer patients with positive expression of PMS-2 and PGP proteins were respectively lower than those of patients with negative expression of PMS-2 and PGP proteins(P<0.05).Cox multivariate regression analysis showed that clinical stage Ⅲ,degree of differentiation,distant metastasis,lymph node metastasis,positive expression of PMS2 protein,positive expression of PGP protein,and preoperative CD4+/CD8+were all influencing factors for the prognosis of patients with gastric cancer(P<0.05).After a 3-year follow-up,the survival curves of gastric cancer patients with negative expressions of PMS2 and PGP protein were respectively higher than those of patients with positive expressions of PMS-2 and PGP protein(P<0.05).Conclusion The expressions of PMS-2 and PGP proteins in gastric cancer tissues are closely associated with clinical stage,presence or absence of lymph node metastasis,degree of tumor differentiation,prognosis and preoperative CD4+/CD8+level.Moreover,patients with positive expressions of PMS-2 and PGP proteins have a worse prognosis.

Aim To explore the effect of the classical famous prescription Dahuang Zhechong pill(DHZCP)on relieving liver cirrhosis by regulating the stress fiber remodeling mediated by mechanistic signaling pathway and to explore the underlying mechanism.Methods Mice were randomly divided into the control group,model group,DHZCP low-dose group,DHZCP high-dose group,and Colchicine-positive control group.The liver cirrhosis mouse model was constructed by intrap-eritoneal injection of olive oil-solubilized CCl4.HE staining and serologic markers were used to reflect liver injury.Masson staining was used to evaluate collagen deposition in liver tissue.ELISA was applied to detect vasoactive molecules and cancer indicators.Atomic force microscopy was employed to detect liver tissue stiffness.Color Doppler diagnostic instrument was used to assess portal blood flow velocity.Western blot was utilized to detect ROCK2 expression and phosphoryla-tion of YAP,Cofilin,and MLC.Results The liver tis-sues in the model group had obvious inflammatory cell infiltration and collagen deposition,accompanied by significant elevation of serum transaminases and fibrosis indexes.Similarly,vasoactive molecules and cancer in-dicators were elevated,and the mechanoregulatory pro-tein ROCK2 expression and phosphorylation of Cofilin and MLC were elevated,with YAP being strongly de-phosphorylated.Both low and high doses of DHZCP re-versed the pathological changes,serological indices,and inhibited the activation of the stress fiber(SF)re-modeling mechanistic signaling pathway.Conclusion DHZCP effectively ameliorates liver tissue lesions in mice with liver cirrhosis,and its mechanism may be re-lated to the inhibition of SF remodeling mechanistic signaling pathway.

Objective To study the consonant articulation performance and speech intelligibility of patients with submucous cleft palate(SMCP)and to provide a reference for clinical speech evaluation and subsequent speech rehabilitation.Methods A total of 333 preoperative SMCP patients aged 4.5 years and older participated in this study.The accuracy,type of error,and error rates were assessed across participant genders and their varying levels of velopharyngeal closure function.Results Among the 333 patients,196 had complete velopharyngeal closure,while 137 had incomplete closure.A total of 145 patients(43.54％)demonstrated normal articulation of all conso-nants,while 188 patients(56.46％)displayed various degrees of articulation disorders.Compensatory articulation behaviors were observed in 66 patients(19.82％).No significant differences in articulation errors were found be-tween male and female patients.The accuracy ranking for consonants was from high to low as follows:nasal sounds,lateral sounds,fricatives,plosives,and affricates.Substitution was the most common error type with an incidence of 35.93％,followed by omission at 34.62％and compensatory errors at 25.51％.The average accuracy rates for plosives,fricatives,affricates,lateral/nasal sounds were 73.27％,78.20％,69.29％,and 93.39％,re-spectively.Substitution was the most common error for plosives and fricatives,while omission was most frequent for affricates.Compensatory errors occurred most often with affricates,and no compensatory errors were found in nasal or lateral sounds.Conclusion Substitution,omission,and compensatory errors are the most common articula-tion errors in SMCP patients,occurring across plosives,fricatives,and affricates.The severity of articulation disor-ders is related to velopharyngeal closure function but is independent of gender.