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 evaluate the efficacy and safety of ruxolitinib combined with low-dose hormone for patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Thirty patients with aGVHD after allo-HSCT admitted to the Department of Hematology of the General Hospital of Western Theater Command from November 2021 to November 2024 were retrospectively analyzed. All patients were treated with low-dose hormone (methylprednisolone 0.3-1 mg kg -d ) combined with ruxolitinib 5-10 mg d . The efficacy and adverse reactions were observed during the follow-up period to analyze the survival outcomes of the patients. Results: A total of 30 patients with aGVHD after allo-HSCT were included in this study, consisting of 15 (50%) males and 15 (50%) females with a median age of 34 year-old (ranging from 14 to 62). Classification by disease type: there were 18 cases of acute myeloid leukemia, 4 cases of acute lymphoblastic leukemia, 4 cases of aplastic anemia, and 4 cases of myelodysplastic syndrome. Classification by aGVHD severity: there were 27 cases (90%) of Ⅱ-Ⅳ degree aGVHD and 11 cases (36.7%) of Ⅲ-Ⅳ degree aGVHD. Ruxolitinib in combination with low-dose glucocorticoid treatment yield responses in 28 (93.3%) patients, of which 27 (90%) achieved complete remission (CR), while 1 (3.3%) showed partial remission (PR). One patient (3.3%) had no response (NR), and 1 patient (3.3%) exhibited progressed disease (PD). Overall survival (OS) at 1 year of transplantation was 73.9% (95%CI 49.5% to 87.7%), progression-free survival (PFS) was 93.3% (95%CI 75.9% to 98.3%), non-relapse mortality (NRM) was 20.6% (95%CI 7.9% to 47.4%), and median survival time was 27.6 months. Conclusion: Ruxolitinib combined with low-dose hormones is safe and effective in the treatment of aGVHD after allo-HSCT.

Bacterial infection is a major threat to global public health,and can cause serious diseases such as bacterial skin infection and foodborne diseases.It is essential to develop a new method to rapidly di-agnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time.In this work,we developed a 4-mercaptophenylboronic acid gold nanoparticles(4-MPBA-AuNPs)-functionalized hydrogel microneedle(MPBA-H-MN)for bacteria detection in skin inter-stitial fluid.MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min.Surface enhanced Raman spectroscopy(SERS)detection was then performed and combined with ma-chine learning technology to distinguish and identify a variety of bacteria.Overall,the capture efficiency of this method exceeded 50％.In the concentration range of 1 × 10 7 to 1 × 10 10 colony-forming units/mL(CFU/mL),the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration.Using random forest(RF)-based machine learning,bacteria were effectively distinguished with an accuracy of 97.87％.In addition,the harmless disposal of used MNs by photothermal ablation was convenient,environmentally friendly,and inexpensive.This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Objective To understand the refractive progression of myopic school-aged children in ethnic minority areas of Yunnan and explore related factors.Methods Based on an existing cohort,a first follow-up survey was conducted from October 2020 to June 2021 involving 1,774 students selected from three ethnic minority areas:Dali City(Bai ethnic group),Lijiang Ancient Town(Naxi ethnic group),and Menghai County in Xishuangbanna(Dai and Hani ethnic groups).Among them,816 myopic school-aged children at baseline were selected as research subjects to analyze changes in refractive error(△SE)and the degree of refractive progression(classified as rapid △SE and slow △SE)over one year.Binary logistic regression was used to analyze the influencing factors of refractive progression.Results After one year of follow-up,the change in refractive error for myopic school-aged children was-0.63(-1.00,-0.25)D,with 518 children experiencing rapid △SE and 298 children experiencing slow △SE.Comparisons by educational stage indicated that Dai ethnic group children in primary school were more likely to experience rapid △SE than those in junior high school(P<0.05).Logistic regression results showed that school-age children of Naxi ethnic group(OR=1.879,95%CI:1.132～2.999),and those who used their eyes in the classroom during breaks(OR=1.541,95%CI:1.088～2.181)were at higher risk of rapid refractive progression(P<0.05).Children of school age who engage in outdoor activities for at least 3 hours during the day(OR=0.539,95%CI:0.340～0.853)and those who frequently consume animal liver(OR=0.596,95%CI:0.399～0.892)have a lower risk of rapid myopic progression(P<0.05).Conclusion Myopic school-aged children in ethnic minority areas of Yunnan exhibit rapid refractive progression,with significant ethnic differen-ces.The refractive progression in these children is closely related to lifestyle habits,highlighting the need for targeted myopia prevention and control measures and research for children and adolescents in ethnic minority areas of Yunnan.

ObjectiveTo develop a reliable and valid health self-management competence assessment questionnaire for primary and secondary school students in Shanghai, so as to provide an effective tool to evaluate and improve their health management competencies. MethodsBased on the theory and process of scale development, an initial item pool was formed. After two rounds of Delphi consultation with 22 experts in related fields, assessment indicators suitable for evaluating the health self-management ability of Shanghai primary and secondary school students were determined. A total of 666 students were selected using stratified cluster sampling method to carry out the survey. The questionnaire content was refined and items were screened for reliability and validity analyses. ResultsAfter the two rounds of Delphi expert consultation, the original three-dimensional structure (individual management behaviors, personal health cognition and self-management environment) was revised into four dimensions: self-health cognition, self-health skills, self-will quality and self-action level. The initial 50 items were reduced, merged, or newly created, yielding a final 30-item questionnaire. Expert response rates for the two rounds of Delphi consultation were 86.36% and 90.91%, respectively, with an expert authority coefficient of 0.91. The KMO value was 0.936 and Bartlett’s sphericity test yielded a P value of <0.001, indicating that the questionnaire demonstrated good construct validity. The results of internal consistency testing showed that the overall Cronbach’s α coefficient was 0.932, and the split-half reliability coefficient was 0.920. The Cronbach’s α coefficient of each dimension ranged from 0.716 to 0.884, and the split-half reliability coefficient ranged from 0.733 to 0.900. Finally, an evaluation scale with 30 items across 4 dimensions was constructed. ConclusionThe health self-management competence evaluation scale for primary and secondary school students in Shanghai demonstrates good homogeneity and high reliability. It can be used as a tool for evaluating the health self-management competency of primary and secondary school students in Shanghai and provide theoretical support for targeted health interventions.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

OBJECTIVE: Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control. METHODS: Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes. RESULTS: Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16. CONCLUSION A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans ; Adenoviruses, Human/isolation & purification* ; Respiratory Tract Infections/epidemiology* ; Child, Preschool ; Child ; Recombination, Genetic ; Male ; Beijing/epidemiology* ; Infant ; Female ; Phylogeny ; Adenovirus Infections, Human/epidemiology* ; Acute Disease ; Genome, Viral

Objective:To investigate the expression of protein kinase D2(PRKD2)in bladder cancer(BLCA)tissue using bioinformatics analysis method and its effect on the prognosis of BLCA patients,and to clarify the role of PRKD2 in the occurrence and development of BLCA.Methods:The data from 9 normal bladder samples,19 BLCA paracancerous samples,and 407 BLCA tumor samples were downloaded from the UCSC Cancer Genome Database.The Mann-Whitney U test was applied to analyze the difference in expression of PRKD2 mRNA in BLCA tumor and normal bladder tissues,and the Human Protein Atlas(HPA)database was used for proteomic validation.DESeq2 package in R software was applied to screen the differentially expressed genes(DEGs)in BLCA tissue in PRKD2 low-and high-expression groups.The co-expression heatmaps of PRKD2 were plotted using the ggplot2 package,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were used for functional annotation analysis and pathway enrichment analysis of DEGs,and Gene Set Enrichment Analysis(GSEA)was used to obtain the gene sets that were significantly enriched for DEGs.The BLCA samples were divided into low-and high-expression groups according to the expression level of PRKD2,and the correlations between PRKD2 expression and immune cell infiltration in the BLCA patients were analyzed with GSVA package.The relationship between PRKD2 and prognosis of BLCA patients was further analyzed using the survival package and the survminer package.The PRKD2 gene mutations in BLCA tissue were analyzed using the cBioPortal database.The cystitis,bladder polyp and BLCA tissues were collected,and the expression levels of interleukin-17F(IL-17F)protein in BLCA and control tissues were detected using immunohistochemical staining technique.Results:PRKD2 was highly expressed in a variety of malignant tumors,and the expression levels of PRKD2 mRNA and protein in BLCA tissue were significantly increased compared with those in normal bladder tissue(P＜0.05).Single gene differential analysis of PRKD2 yielded a total of 1 058 DEGs,of which a total of 29 genes were up-regulated and 1 029 were down-regulated.The results of GO functional enrichment analysis showed that DEGs were mainly enriched in the biological process(BP),such as chemical stimuli involved in sensory perception,Cajal body,and endopeptidase inhibitor activity.The results of KEGG pathway analysis showed that DEGs were mainly enriched in the pathway of Staphylococcus aureus infection and the pathway of maturity onset diabetes of the young.GSEA analysis showed that DEGs were mainly enriched in the Notch signaling pathway,the retinoic acid-inducible gene-Ⅰ(RIG-Ⅰ)-like receptor signaling pathway,the cytoplasmic DNA screening pathway,the base excision repair signaling pathway,natural killer(NK)cell-mediated cytotoxicity signaling pathway and T cell receptor signaling pathway.The results of immune infiltration analysis indicated that the expression of PRKD2 was positively correlated with five types of cells,such as activated dendritic cells(aDC),NK CD56dim cells and central memory T cells(Tcm)(P＜0.05),and negatively correlated with three types of immune cells,including macrophages,effector memory T cells(Tem)and plasmacytoid dendritic cells(pDC)(P＜0.05).The clinical characteristic subgroup analysis results showed that the expression levels of PRKD2 mRNA in BLCA patients who were over 70 years old and developed lymphovascular invasion were decreased(P＜0.05);the overall survival(OS),disease-specific survival(DSS)and progression-free interval(PFI)in the BLCA patients with PRKD2 high expression were significantly longer than those with PRKD2 low expression(P＜0.05).The univariate and multivariate Cox analyses indicated that distant metastasis,primary therapy outcome and clinicopathologic stage were the important factors affecting BLCA prognosis.About 9％patients had PRKD2 gene mutations,including missense mutation,gene amplification,mRNA low or high expression,and multi-motif mutation.The immunohistochemistry results showed that the expression level of IL-17F protein in BLCA tissue was significantly higher than that in cystitis tissue(P＜0.05).Conclusion:The expression level of PRKD2 in BLCA tissue is obviously increased,which could up-regulate the expression of IL-17F protein,and the decrease of PRKD2 protein expression may be a potential factor for the poor prognosis of BLCA patients.

OBJECTIVE: To investigate platelet count trajectories after induction therapy with venetoclax combined with azacitidine (VA regimen) in newly diagnosed AML patients and further analyze its clinical significance. METHODS: Clinical date of 50 newly diagnosed AML patients who received VA treatment from March 2020 to July 2023 in Department of Hematology of the First Hospital of Lanzhou University were retrospectively collected. The platelet trajectories after induction chemotherapy were constructed by using group-based trajectory modeling. To study the association between diverse trajectories of platelet counts and compound complete remission (cCR) rate, overall response rate (ORR), minimal residual disease (MRD) negative rate and overall survival (OS) rate. The Cox proportional hazard model was used to evaluate the relationship between platelet trajectory and OS. The logistic regression was used to analyze the influence of individual characteristics on platelet trajectory. RESULTS: Two platelet trajectories were identified based on the model, including platelet slowly increased group (n=31, 62.0%) and platelet rapidly increased group (n=19, 38.0%). There were statistically significant differences in cCR rate, ORR and OS rate between platelet slowly increased group and platelet rapidly increased group (all P < 0.05). The Cox regression analysis showed that platelet rapidly increased group was associated with a decreased risk of mortality compared with platelet slowly increased group (HR=0.153, 95%CI : 0.045-0.527, P =0.003). Logistic regression analysis showed that IDH1/2 mutation (OR =3.908, 95%CI : 1.023-14.923, P =0.046) and platelet transfusion (OR =0.771, 95%CI : 0.620-0.959, P =0.020) were independent influencing factors of platelet trajectory. CONCLUSION The dynamic trajectory of platelet counts in newly diagnosed AML patients who received VA treatment can serve as a significant indicator to observe the efficacy and prognosis. The platelet rapidly increased is an independent protective factor for good prognosis. TheIDH1 /2 mutation and platelet transfusion are independent influencing factors of platelet trajectory.
Humans ; Leukemia, Myeloid, Acute/blood* ; Sulfonamides/administration & dosage* ; Azacitidine/therapeutic use* ; Platelet Count ; Retrospective Studies ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Induction Chemotherapy ; Survival Rate