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 To investigate the association between rest-activity rhythm(RAR)and the risks of rheumatoid arthritis(RA),and to evaluate whether genetic susceptibility modifies this relationship.Methods This prospective cohort study utilized data from the UK Biobank,including 88 060 participants who did not have RA at baseline.RAR parameters(e.g.,relative amplitude)were calculated using data obtained through wrist-worn accelerometers.The participants'genetic susceptibility to RA was assessed using a polygenic risk score.Cox proportional hazards models were employed to analyze the association between RAR and RA risk,with interaction terms incorporated to evaluate the effect modification by genetic susceptibility.Results Over a median follow-up period of 7.97 years,660 incident RA cases were identified.After adjusting for age,sex,ethnicity,educational attainment,Townsend deprivation index,drinking status,smoking status,dietary score,body mass index,and polygenic risk score for incident RA,the dose-response analysis revealed a linear relationship between the RAR-related parameters,including the average amplitude during the most active 10 h(M10),interdaily stability(IS),intradaily variability(IV),and the risk of developing RA(P>0.05).In contrast,relative amplitude and the average amplitude during the least active 5 h(L5)showed a nonlinear relationship with the risk of developing RA(P<0.05).Compared to those in the the highest quartile of relative amplitude,participants in the lowest quartile had a 49%increase in the risk of developing RA(hazard ratio[HR]=1.49;95%CI,1.17-1.90).Compared to those in the lowest quartile,participants in the highest quartile of L5 had a 40%increased risk of developing RA(HR=1.40;95%CI,1.12-1.75).Every time M10 increased by one standard deviation,the risk of developing RA decreased by 12%(HR=0.88;95%CI,0.80-0.96).No evidence of effect modification by genetic susceptibility was observed in the RAR-RA association(P>0.05).Conclusion Disrupted rest-activity rhythm is associated with an increased risk of RA,which is independent of genetic susceptibility to RA.Our findings suggest that improving rest-activity rhythm may help reduce RA risks.

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.

Objective:To understand the composition of infectious pathogens and the changes in the epidemic characteristics of inpatients with acute respiratory tract infections in Pudong New Area of Shanghai, from 2018 to 2023.Methods:Specimens of inpatients with acute respiratory infection cases were collected from 14 healthcare institutions in Pudong New Area, Shanghai, from 2018-2023 and tested for eight respiratory pathogens: influenza virus, adenovirus, rhinovirus, parainfluenza virus, respiratory syncytial virus, common coronavirus, metapneumovirus, and bocavirus. The groups were divided into three periods,2018-2019, 2020-2022 and 2023, and the chi-square or Kruskal-Wallis rank sum test was used to compare the group differences. The SPSS 22.0 software was used for statistical analysis.Results:Among the 3 023 inpatients with acute respiratory infection, the positive rate of any virus was 24.25% (733/3 023). The positive rates of any virus in 2018-2019, 2020-2022, and 2023 were 33.40% (336/1 006), 12.01% (116/966), and 26.74% (281/1 051), respectively, and the differences were statistically significant ( χ2=128.20, P<0.001). Among the age groups, in 2018-2019 and 2020-2022, the positive rate of any virus was the highest in the <5 years age group (46.20% and 14.64%), while in 2023, the 15-59 years age group had the highest positive rate (32.97%). The positive rate of any virus in winter was the highest in 2018-2019 (53.21%) and 2020-2022 (17.58%), and the highest in autumn was in 2023 (31.53%). The peak positive rate of respiratory syncytial virus was in winter of 2018-2019 and 2020-2022, as well as the summer of 2023.The positive rates of influenza virus in 2018-2019, 2020-2022 and 2023 were 9.84%, 1.55% and 9.71%, respectively. Conclusions:The pathogen epidemic characteristics of inpatients with acute respiratory infection in Pudong New Area from 2018 to 2023 have shown certain changes. It is necessary to strengthen monitoring. Targeted prevention and control strategies should be developed and implemented in a timely manner.

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.

Objective:To understand the composition of infectious pathogens and the changes in the epidemic characteristics of inpatients with acute respiratory tract infections in Pudong New Area of Shanghai, from 2018 to 2023.Methods:Specimens of inpatients with acute respiratory infection cases were collected from 14 healthcare institutions in Pudong New Area, Shanghai, from 2018-2023 and tested for eight respiratory pathogens: influenza virus, adenovirus, rhinovirus, parainfluenza virus, respiratory syncytial virus, common coronavirus, metapneumovirus, and bocavirus. The groups were divided into three periods,2018-2019, 2020-2022 and 2023, and the chi-square or Kruskal-Wallis rank sum test was used to compare the group differences. The SPSS 22.0 software was used for statistical analysis.Results:Among the 3 023 inpatients with acute respiratory infection, the positive rate of any virus was 24.25% (733/3 023). The positive rates of any virus in 2018-2019, 2020-2022, and 2023 were 33.40% (336/1 006), 12.01% (116/966), and 26.74% (281/1 051), respectively, and the differences were statistically significant ( χ2=128.20, P<0.001). Among the age groups, in 2018-2019 and 2020-2022, the positive rate of any virus was the highest in the <5 years age group (46.20% and 14.64%), while in 2023, the 15-59 years age group had the highest positive rate (32.97%). The positive rate of any virus in winter was the highest in 2018-2019 (53.21%) and 2020-2022 (17.58%), and the highest in autumn was in 2023 (31.53%). The peak positive rate of respiratory syncytial virus was in winter of 2018-2019 and 2020-2022, as well as the summer of 2023.The positive rates of influenza virus in 2018-2019, 2020-2022 and 2023 were 9.84%, 1.55% and 9.71%, respectively. Conclusions:The pathogen epidemic characteristics of inpatients with acute respiratory infection in Pudong New Area from 2018 to 2023 have shown certain changes. It is necessary to strengthen monitoring. Targeted prevention and control strategies should be developed and implemented in a timely manner.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

The holistic view is the key in the study of traditional Chinese medicine(TCM). The component structure theory is based on the holistic view to investigate the correlation between material basis and efficiency, which enriches the holistic "component-effect" research of TCM. Gintonin is a newly isolated non-saponin component of ginseng. Compared to ginsenosides, gintonin has many different pharmacological activities, and it provides new knowledge for the holistic research of ginseng. Thus, taking the discovery of gintonin from ginseng as an example, this paper explored the linkage between ginsenosides and gintonin from the perspective of "component-effect" correlations and systematically sorted out the similarities and differences between them in terms of structural characteristics, modes of action, and pharmacological activities. Starting from the collaborative interaction of TCM compounds, the study discussed the application and value of the holistic view in TCM "component-effect" research in the light of the component structure theory to provide new thoughts for the development of modern TCM research.
Panax/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional ; Humans ; Ginsenosides/pharmacology* ; Animals

This study aimed to investigate the correlation between changes in intestinal toxicity and compositional alterations of Euphorbiae Ebracteolatae Radix(commonly known as Langdu) before and after milk processing, and to explore the detoxification mechanism of milk processing. Mice were intragastrically administered the 95% ethanol extract of raw Euphorbiae Ebracteolatae Radix, milk-decocted(milk-processed), and water-decocted(water-processed) Euphorbiae Ebracteolatae Radix. Fecal morphology, fecal water content, and the release levels of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in different intestinal segments were used as indicators to evaluate the effects of different processing methods on the cathartic effect and intestinal inflammatory toxicity of Euphorbiae Ebracteolatae Radix. LC-MS/MS was employed to analyze the small-molecule components in the raw product, the 95% ethanol extract of the milk-processed product, and the milky waste(precipitate) formed during milk processing, to assess the impact of milk processing on the chemical composition of Euphorbiae Ebracteolatae Radix. The results showed that compared with the blank group, both the raw and water-processed Euphorbiae Ebracteolatae Radix significantly increased the fecal morphology score, fecal water content, and the release levels of TNF-α and IL-1β in various intestinal segments(P<0.05). Compared with the raw group, all indicators in the milk-processed group significantly decreased(P<0.05), while no significant differences were observed in the water-processed group, indicating that milk, as an adjuvant in processing, plays a key role in reducing the intestinal toxicity of Euphorbiae Ebracteolatae Radix. Mass spectrometry results revealed that 29 components were identified in the raw product, including 28 terpenoids and 1 acetophenone. The content of these components decreased to varying extents after milk processing. A total of 28 components derived from Euphorbiae Ebracteolatae Radix were identified in the milky precipitate, of which 27 were terpenoids, suggesting that milk processing promotes the transfer of toxic components from Euphorbiae Ebracteolatae Radix into milk. To further investigate the effect of milk adjuvant processing on the toxic terpenoid components of Euphorbiae Ebracteolatae Radix, transmission electron microscopy(TEM) was used to observe the morphology of self-assembled casein micelles(the main protein in milk) in the milky precipitate. The micelles formed in casein-terpenoid solutions were characterized using particle size analysis, fluorescence spectroscopy, ultraviolet spectroscopy, and Fourier-transform infrared(FTIR) spectroscopy. TEM observations confirmed the presence of casein micelles in the milky precipitate. Characterization results showed that with increasing concentrations of toxic terpenoids, the average particle size of casein micelles increased, fluorescence intensity of the solution decreased, the maximum absorption wavelength in the UV spectrum shifted, and significant changes occurred in the infrared spectrum, indicating that interactions occurred between casein micelles and toxic terpenoid components. These findings indicate that the cathartic effect of Euphorbiae Ebracteolatae Radix becomes milder and its intestinal inflammatory toxicity is reduced after milk processing. The detoxification mechanism is that terpenoid components in Euphorbiae Ebracteolatae Radix reassemble with casein in milk to form micelles, promoting the transfer of some terpenoids into the milky precipitate.
Animals ; Mice ; Milk/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Male ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/drug effects* ; Interleukin-1beta/immunology* ; Tandem Mass Spectrometry ; Female