ObjectiveTo investigate the regulatory effect of overexpressed protein tyrosine phosphatase non-receptor type 2 （Ptpn2） on the inflammatory response of mouse alveolar macrophages （MH-S） induced by SiO₂. MethodsCells with overexpressed Ptpn2 were constructed and induced by SiO₂. The experimental groups were divided into four groups： the negative control group with an empty vector （NC）， the overexpressed Ptpn2 group （P）， the negative control group with an empty vector + SiO₂ induction （NS）， and the overexpressed Ptpn2 + SiO₂ induction group （PS）. Isobaric tags for relative and absolute quantification （iTRAQ） combined with liquid chromatography-tandem mass spectrometry （LC-MS/MS） were used to screen differential proteins， followed by Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） database analyses. Immunofluorescence staining was used to detect the expressions of Tumor necrosis factor （TNF） α， Gasdermin D （GSDMD）， and Transforming growth factor （TGF）-β1. Western blot was used to detect the protein expression levels of PTPN2， Toll-like receptor 4 （TLR4）， tumor necrosis factor-α （TNF-α）， nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3）， and proteins related to the TGF-β1 signaling pathway in the cells of each group. ResultsiTRAQ results identified 144 differential proteins among the four groups. GO analysis showed that in biological processes （BP）， these differential proteins were mainly enriched in IκB kinase/nuclear factor-κB （NF-κB） signaling， cell activation and signal transduction involved in immune responses， and regulation of receptor signaling pathways by signal transducer and activator of transcription （STAT）， etc. KEGG analysis revealed that the differential proteins were mainly enriched in Toll-like receptor signaling pathway， NF-κB signaling pathway， NOD-like receptor signaling pathway， TGF-β signaling pathway， and TNF signaling pathway. The results of immunofluorescence staining showed that compared with the NC group， the expressions of TNF α， GSDMD， and TGF-β1 in the cells of the NS group increased （P < 0.05）； compared to the NS group， the expression of the aforementioned proteins in the PS group decreased in cellular proteins（P < 0.05）. The results of Western blot showed that compared with the NC group， the protein expression levels of PTPN2， p-NF-κB，MyD88，TLR4，NLRP3，GSDMD，Caspase-1，IL-1β， TGF-βR1， TGF-βR，p-Smad2/3 in the NS group were significantly upregulated （P < 0.05）； compared with the NS group， the expression levels of the aforementioned proteins in the PS group were significantly downregulated （P < 0.05）. ConclusionOverexpression of Ptpn2 can inhibit the protein expressions of TLR4-TNF-α signaling， NLRP3 signaling， and TGF-β1 signaling closely related to inflammatory response in SiO₂-mediated MH-S macrophages.

Glycogen synthase 1 (GYS1) is the rate-limiting enzyme responsible for glycogen synthesis in skeletal muscle, heart, brain, and other extrahepatic tissues, playing a central role in systemic energy homeostasis. The human GYS1 gene maps to chromosome 19q13.33, comprises 16 exons, and encodes a 737-amino-acid polypeptide that is highly conserved across mammals. GYS1 activity is subject to multilayered and precisely coordinated regulation. At the transcriptional level, the GYS1 promoter contains a hypoxia response element (HRE) that mediates HIF-1α-dependent induction under low-oxygen conditions, as well as a muscle-specific enhancer harboring MEF2 and MyoD binding sites that confers tissue-restricted expression. At the post-translational level, a hierarchical phosphorylation cascade serves as the primary activity switch: glycogen synthase kinase 3β (GSK3β) sequentially phosphorylates four C-terminal serine residues following casein kinase II priming, while protein kinase A (PKA) and AMP-activated protein kinase (AMPK) provide parallel inhibitory inputs at both N- and C-terminal sites. Dephosphorylation and reactivation are mediated by protein phosphatase 1 (PP1) through tissue-specific glycogen-targeting regulatory subunits such as PPP1R3A and PPP1R3B, which anchor PP1 to glycogen particles and direct its activity toward GYS1. The allosteric activator glucose-6-phosphate (G6P) binds at the dimer interface, simultaneously enhancing catalytic efficiency and promoting dephosphorylation susceptibility, thereby establishing a feed-forward activation loop that couples substrate availability to glycogen synthesis. Beyond phosphorylation, GYS1 is regulated by ubiquitination (mediated by the E3 ligase PJA1), acetylation, O-linked β-N-acetylglucosamine (O-GlcNAc) modification, and SUMOylation, which collectively modulate protein stability, subcellular localization, and protein-protein interactions. Epigenetic mechanisms, including CpG island methylation and histone acetylation dynamics, govern chromatin accessibility at the GYS1 locus, while muscle-specific microRNAs such as miR-1 and miR-206 fine-tune GYS1 expression at the post-transcriptional level. Dysregulation of GYS1 has been identified as a central pathogenic driver in a spectrum of human diseases. In inherited glycogen storage disorders—including Lafora disease, adult polyglucosan body disease (APBD), and Pompe disease—loss of upstream regulatory control leads to GYS1 hyperactivation and the accumulation of structurally abnormal or excessive glycogen, resulting in progressive neurodegeneration, myopathy, and multiorgan dysfunction. In type 2 diabetes mellitus (T2DM), impaired insulin signaling through the PI3K-AKT-GSK3β axis maintains GYS1 in a hyperphosphorylated inactive state in skeletal muscle, compromising postprandial glucose disposal and exacerbating hyperglycemia. In oncology, GYS1 exhibits context-dependent roles across multiple cancer types. In hepatocellular carcinoma, FMO2⁺ cancer-associated fibroblasts stabilize GYS1 by competitively inhibiting PJA1-mediated ubiquitination, and stabilized GYS1 subsequently activates NF‑κB/CCL19 signaling to promote tertiary lymphoid structure formation and enhance anti-PD-1 immunotherapy responsiveness. In clear cell renal cell carcinoma, GYS1 promotes tumor progression through non-canonical NF‑κB pathway activation via the scaffold protein RPS27A. In triple-negative breast cancer, GYS1 has been identified as a trigger of disulfidptosis and an activator of NF-κB signaling through non-enzymatic facilitation of IκBα degradation. In colorectal cancer, mitochondrial fission deficiency drives AMPK-dependent GYS1 upregulation and glycogen accumulation as a compensatory survival mechanism, while in cervical cancer, GYS1-maintained glycogen reserves fuel the pentose phosphate pathway to generate NADPH for ROS clearance, thereby conferring cisplatin resistance in cancer stem cells. Therapeutic strategies targeting GYS1 have gained substantial momentum across these disease contexts. For glycogen storage disorders, antisense oligonucleotides, small interfering RNAs (e.g., ABX1100), and small-molecule inhibitors (e.g., MZ-101) have demonstrated preclinical and early clinical efficacy in reducing pathological glycogen accumulation. For T2DM, pharmacological activation of GYS1 through GSK3β inhibition or enhancement of PP1-mediated dephosphorylation is being explored to restore insulin-stimulated glycogen synthesis. In cancer, GYS1-directed interventions—including targeted silencing to sensitize tumors to chemotherapy and immune microenvironment modulation to enhance immunotherapy—represent emerging precision oncology approaches. This review provides a comprehensive and integrated account of GYS1 gene structure, tissue-specific distribution, regulatory networks, and pathogenic roles in metabolic disorders and malignancies, with the aim of establishing a theoretical framework for the development of GYS1-targeted precision therapies.

Background::B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.Methods::Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM at the First Affiliated Hospital, School of Medicine, Zhejiang University was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.Results::In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow ( P = 0.0125), lower percentages of CAR-T cells in the peripheral blood at peak ( P = 0.0375), and higher percentages of CD8 + T cells ( P = 0.0340). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) ( P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [ P = 0.004], IRF4 [ P = 0.024], and CREBBP [ P = 0.041]), number of multisite mutations, and resistance-related mutation ( ERBB4, P = 0.040) were independent risk factors for PFS. Conclusion::Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.

AIM To investigate the renal protective effects of Qizhi Tongluo Formula on a mouse model of diabetic nephropathy.METHODS The male db/db mice were randomly divided into the model group,the dapagliflozin group(0.76 mg/kg)and the low,medium and high dose Qizhi Tongluo Formula groups(7.83,15.65 and 31.3 g/kg),with 6 mice in each group,in contrast to the 6 db/m mice of the control group.When the mice of the control group and the model group were given distilled water by gavage,those of the other administration groups were dosed with the corresponding drug by gavage once daily for 8 weeks.After the drug administration,the mice had their levels of FBG,BUN,Scr and 24 h-UTP detected;their renal pathological changes observed by transmission electron microscopy(TEM)and HE staining;their levels of serum Nrf2,HO-1,Keap1 and renal oxidative stress assessed by ELISA;their renal Nrf2 protein expression observed by immunofluorescence(IF);their renal protein expressions of Nrf2,HO-1 and Keap1 detected by Western blot;and their renal Nrf2,HO-1,and Keap1 mRNA expressions detected by RT-qPCR.RESULTS Compared with the control group,the model group displayed increased levels of 24 h-UTP,Scr,FBG and renal MDA(P＜0.01);decreased renal activities of SOD,CAT and GSH-Px(P＜0.01);mild glomerular mesangial hyperplasia,vacuolated renal tubular epithelial cells,widely fused podocyte foot processes,disappearance of tear film,decreased secretion levels of serum Nrf2 and HO-1 and renal protein and mRNA expressions of Nrf2 and HO-1(P＜0.05,P＜0.01);and decreased secretion levels of serum Keap1 and renal Keap1 protein and mRNA expressions(P＜0.01).Compared with the model group,the high-dose Qizhi Tongluo Formula group demonstrated decreased levels of 24 h-UTP,Scr,FBG and renal MDA(P＜0.01);increased renal activities of SOD,CAT and GSH-Px(P＜0.01);alleviated renal pathological damage,increased secretion levels of serum Nrf2 and HO-1 and renal protein and mRNA expressions of Nrf2 and HO-1(P＜0.01);and increased level of serum Keap1 secretion and renal Keap1 protein and mRNA expressions(P＜0.01).CONCLUSION Qizhi Tongluo Formula can inhibit oxidative stress and alleviate kidney damage in db/db mice by activating Nrf2/Keap1/ARE signaling pathway.

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China

OBJECTIVES: To investigate the incidence of myocardial injury in children with rotavirus-induced diarrhea, analyze its risk factors, and develop a predictive model for myocardial injury. METHODS: A retrospective analysis was conducted on 203 children diagnosed with rotavirus infection at the Suzhou Wujiang District Children's Hospital from January 2021 to December 2023. The children were divided into groups based on the presence or absence of myocardial injury. Basic information and laboratory indicators at admission were collected and compared between the two groups. LASSO regression was used to screen potential risk factors, followed by multivariate logistic regression to evaluate independent factors. A nomogram model was established and validated. RESULTS: Out of 203 children with rotavirus infection, 53 cases (26.1%) showed myocardial injury. Age, severe dehydration, metabolic acidosis, red cell distribution width, and blood sodium were closely associated with myocardial injury in children with rotavirus-induced diarrhea (P<0.05). The area under the receiver operating characteristic curve for the predictive model of myocardial injury was 0.841 (95%CI: 0.777-0.905), with a sensitivity of 73.6% and specificity of 85.3%. The model curve closely fit the ideal diagonal line. Decision curve analysis showed that using the model for prediction resulted in the highest net benefit when the probability threshold was 0.18-0.98. CONCLUSIONS The model developed in this study can predict the risk of myocardial injury in children with rotavirus-induced diarrhea.
Humans ; Rotavirus Infections/complications* ; Diarrhea/etiology* ; Male ; Female ; Infant ; Retrospective Studies ; Risk Factors ; Child, Preschool ; Logistic Models ; Child

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.

Objective To explore the predictive value of albumin,hemoglobin and multifactorial model for poor postoperative prognosis in elderly patients with meningioma.Methods A retrospective analysis was conducted on 253 elderly patients who underwent meningioma surgery and were transferred to the neurosurgical intensive care unit(NICU)at General Hospital of Northern Theater Command from January 2019 to September 2021,serving as the modeling cohort.Another 227 elderly patients who were treated in NICU after meningioma surgery from November 2021 to June 2023 were used as the validation cohort.Patients in the modeling cohort were categorized into good prognosis group[Glasgow Coma Scale(GCS)score>7,n=161]and poor prognosis group(GCS≤7,n=92)based on the GCS.Univariate and multifactorial logistic regression analyses were performed on the modeling cohort to identify independent risk factors,and a multifactorial model for predicting poor postoperative prognosis in elderly patients with meningioma was constructed based on these factors.The predictive efficacy and accuracy of the model were evaluated using the area under the receiver operating characteristic(ROC)curve(AUC),sensitivity,specificity,Hosmer-Lemeshow goodness-of-fit test,and calibration curves.The predictive value of postoperative albumin,hemoglobin,and the multifactorial models for postoperative prognosis in elderly meningioma patients was assessed using restricted cubic spline modeling(RCS),decision curves(DCA),and validated using an external validation cohort to assess the stability of the model.Results Meningioma WHO grade Ⅱand Ⅲ(OR=3.994,95％CI 1.963-8.126),postoperative hypoalbuminemia(OR=2.194,95％CI 1.079-4.462),and postoperative anemia(OR=2.117,95％CI 1.096-4.089)were identified as independent risk factors for poor postoperative prognosis in elderly meningioma patients(P<0.05),while the use of analgesic/sedative medications was a protective factor(OR=0.388,95％CI 0.201-0.748,P<0.05).The Hosmer-Lemeshow test indicated that the constructed multifactorial model had a good fit accuracy(P=0.161).The AUC for predicting poor postoperative prognosis in elderly meningioma patients for postoperative albumin and hemoglobin were 0.545(95％CI 0.472-0.617)and 0.632(95％CI 0.561-0.702),respectively,and showed a nonlinear dose-response relationship with prognosis(P<0.01).DCA analysis results showed that the net benefit rate of multifactorial model was higher than that of postoperative albumin and hemoglobin when the threshold probabilities were between 0.10 and 0.90.The AUC for predicting postoperative prognosis in the elderly meningioma patients in the modeling and validation cohorts were 0.810 and 0.819,respectively,and their calibration curves suggested good discrimination and accuracy.Conclusions Meningioma WHO grades Ⅱ and Ⅲ,postoperative anemia and hypoalbuminemia are independent risk factors for poor postoperative prognosis in elderly meningioma patients,while the use of analgesic/sedative drugs is a protective factor.The multifactorial model constructed based on these factors has a good predictive efficacy and credibility,and can be used as a reference for clinical decision-making.

OBJECTIVE: To investigate the effect of TBL1XR1 mutation on cell biological characteristics of diffuse large B-cell lymphoma (DLBCL). METHODS: The TBL1XR1 overexpression vector was constructed and DNA sequencing was performed to determine the mutation status. The effect of TBL1XR1 mutation on apoptosis of DLBCL cell line was detected by flow cytometry and TUNEL fluorescence assay; CCK-8 assay was used to detect the effect of TBL1XR1 mutation on cell proliferation; Transwell assay was used to detect the effect of TBL1XR1 mutation on cell migration and invasion; Western blot was used to detect the effect of TBL1XR1 mutation on the expression level of epithelial-mesenchymal transition (EMT) related proteins. RESULTS: The TBL1XR1 overexpression plasmid was successfully constructed. The in vitro experimental results showed that TBL1XR1 mutation had no significant effect on apoptosis of DLBCL cells. Compared with the control group, TBL1XR1 mutation enhanced cell proliferation, migration and invasion of DLBCL cells. TBL1XR1 gene mutation significantly increased the expression of N-cadherin protein, while the expression of E-cadherin protein decreased. CONCLUSION TBL1XR1 mutation plays a role in promoting tumor cell proliferation, migration and invasion in DLBCL. TBL1XR1 could be considered as a potential target for DLBCL therapy in future research.
Humans ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Cell Proliferation ; Mutation ; Receptors, Cytoplasmic and Nuclear/genetics* ; Apoptosis ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Cell Movement ; Repressor Proteins/genetics* ; Nuclear Proteins/genetics* ; Cadherins/metabolism*

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*