Objective: To fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials. Methods: The hydrogel framework (designated DF0) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF1, while the co-loaded hydrogel was named DF2. The self-mineralization efficacy of the DF0 , DF1 and DF2 hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF0 , DF1 and DF2 hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group Results: The DF0, DF1, and DF2 hydrogels were successfully synthesized. Notably, DF1 and DF2 exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF1, and amorphous calciumzinc phosphate in group DF2. Biocompatibility tests revealed that none of the hydrogels (DF0, DF1, and DF2) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF1 and DF2 groups, with the most profound staining observed in the DF2 group. Conclusion The developed inositol hexaphosphate-zinc hydrogel (DF2) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.

ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription （XLHZ） in treating chronic atrophic gastritis （CAG） by regulating cell cycle and inhibiting proliferation， using bioinformatics technology and animal experiments. MethodsDifferential expressed genes （DEGs） related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis （WGCNA） was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction （PPI） analysis of genes was conducted using the Protein Interaction Platform （STRING） database to search the super hub gene （hub 2.0）， and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group， and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine （MNNG） + sodium salicylate". The successfully modeled rats were randomly divided into the model group， XLHZ-H， XLHZ-M， and XLHZ-L groups （36， 18， 9 g·kg^-1， respectively）， and Morodan group （1.4 g·kg^-1）. Each group was given corresponding intervention for 60 days. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β₁， Smad2 and Smad3 proteins， S/G₂/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue， and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified， including TGF-β₁， suggesting the involvement of the TGF-β₁ signaling pathway in the CAG pathogenesis. Compared with the normal group， the expressions of TGF-β₁， Smad2， geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased （P<0.05）， and the expression of Smad3 protein was decreased （P<0.05）. Compared with the model group， the expressions of TGF-β₁ and geminin in the gastric mucosa were decreased in the drug groups （P<0.05）. The XLHZ-M group， XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 （P<0.05）. The protein expression of Smad3 was significantly increased in XLHZ-M， XLHZ-H， and Morodan groups （P<0.05）. Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators， and positively correlated with other indicators （P<0.01）. ConclusionXLHZ may inhibit TGF-β₁/Smads signaling pathway， regulate cell cycle， and inhibit proliferation in the treatment of CAG.

Objective: To understand the current status of psychological sub health among secondary vocational school students and explore its related factors, so as to provide a scientific basis for improving their mental health. Methods: From September to December 2024, a convenience sampling method was used to conduct a questionnaire survey among 5 141 secondary vocational school students from 16 schools across 8 provinces and municipalities (Fujian, Chongqing, Guangdong, Guangxi, Hubei, Jiangxi, Shanghai, Zhejiang). A self designed questionnaire was used to collect data on students demographic characteristics and lifestyle behaviors. The Multidimensional Sub health Questionnaire of Adolescents was adopted to assess psychological sub health status. Multivariate binary Logistic stepwise regression analysis was performed to explore the related factors of psychological sub health among secondary vocational school students. Results: The detection rate of psychological sub health among secondary vocational school students was 11.0%, with detection rates of emotional problems, conduct problems, and social adaptation difficulty being 12.3 %, 12.5%, and 9.5%, respectively. Logistic regression analysis revealed that boys and students whose fathers had an educational level of primary school or below, and junior high school, had relatively lower risks of developing psychological sub health or emotional problems, conduct problems, and social adaptation difficulty ( OR =0.55-0.64, all P <0.05). Conversely, students with urban household registration, those with left behind experience, those with poor self rated family economic status, those from other family structures, those classified as overweight and obesity, and those with sleep disorders, frequent consumption of sugar sweetened beverages, frequent consumption of takeout/delivery food, smoking, alcohol consumption, and low to moderate physical activity levels exhibited significantly higher risks across psychological sub health or emotional problems,conduct problems, and social adaptation difficulty ( OR =1.25-4.79, all P <0.05). Conclusions The psychological sub health condition of secondary vocational school students should not be neglected. Psychological sub health of secondary vocational school students is related to multiple factors such as demographic characteristics and lifestyle behaviors. Multi dimensional intervention measures should be implemented to improve their mental health.

OBJECTIVE: To investigate the clinical phenotypic and genetic characteristics of three children with Paroxysmal kinesigenic dyskinesia (PKD) and Self-limited familial infantile epilepsy (SeLIE) caused by PRRT2 gene mutation. METHODS: Three children with PKD and SeLIE caused by PRRT2 gene mutation (children 1-3) who were treated in the First Affiliated Hospital of Zhengzhou University from November 2022 to August 2023 were selected as the research subjects. A retrospective study was conducted to collect the clinical and family history data of the three children. 2 mL of peripheral venous blood from children 1-3 and parents of children 1-2 were collected (parents of children refused to undergo genetic testing and no blood samples were collected), genomic DNA was extracted, whole exome sequencing (WES) was performed, and Sanger sequencing method was used for verification. According to the Classification Standards and Guidelines for Genetic Variants formulated by the American Society of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the "ACMG Guidelines"), the pathogenicity of the variant loci detected in three children was rated, and the detrimental loci of the variant loci were analyzed by multiple bioinformatics software. This study has been approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2024-KY-0881-002). RESULTS: The clinical data and genetic test results of the three children in this study are as follows. Child 1: female, age of onset of 4 months and 10 days, with seizures, manifested as sudden cessation of movements, staring in both eyes, cyanosis of the lips, paleness, and stiffness and shaking of limbs. The results of genetic testing showed that child 1 had maternal PRRT2 gene c.583_584dup (p.P196Afs*34) frameshift variant, which was rated as a pathogenic variant (PVS1 PM2_Supporting PP4) according to ACMG guidelines. According to the clinical manifestations and genetic test results of child 1, he was diagnosed with SeLIE and took oral sodium valproate [0.5 mL/(kg.d)], and was still taking medication at the follow-up of 2 years old, and did not have seizures again after 5 months of age. Child 2: male, age of onset of 10 years old, manifested as dystonia after sudden movement. The results of genetic testing showed that child 2 had PRRT2 gene mutations: paternal c.649dupC (p.R217Pfs*8) frameshift variant and maternal c.445C>A (p.Q149K) mutation. Among them, c.649dupC was a reported pathogenic variant, and according to ACMG guidelines, c.445C>A variant was rated as a variant of unknown clinical significance (PM2_Supporting), with a high probability of benignness. According to the clinical manifestations and genetic test results of the child 2, he was diagnosed with PKD, and was followed up with oral oxcarbazepine 9 mg/(kg.d) until 12 years and 2 months, and was still on the drug, and there was no recurrence of the seizure of the form of dyskinesia after taking the drug. Child 3: male, age of onset of 11 years old, manifested by dystonia after sudden exercise. The results of genetic testing showed that child 3 had a missense variant of PRRT2 gene c.904G>C (p.D302H), and his parents refused genetic testing, and the source of the mutation was unknown, and the variant was rated as a variant of unknown clinical significance (PM2_Supporting+PP3_Moderate+PP4) according to ACMG guidelines. According to the clinical manifestations and genetic test results of child 3, he was diagnosed with PKD, and was treated with oral oxcarbazepine 10 mg/(kg.d) for 1 year and then discontinued on his own, and was followed up at the age of 17, and there was no recurrence of the seizure of the form of movement disorder after taking the drug. CONCLUSION One case of SeLIE and two cases of PKD caused by PRRT2 gene mutations responded well to anti-seizure drugs. In this study, four variant loci of PRRT2 gene were found: c.583_584dup, c.904G>C, c.649dupC, c.445C>A, among which c.583_584dup were new variants, enriching the variant spectrum of PRRT2 gene.
Humans ; Male ; Nerve Tissue Proteins/genetics* ; Female ; Membrane Proteins/genetics* ; Mutation ; Child, Preschool ; Infant ; Phenotype ; Dystonia/genetics* ; Retrospective Studies ; Child

OBJECTIVE: To analyze the clinical characteristics and genetic etiology of a child with Christianson syndrome (CS). METHODS: A 1-year-and-5-month-old boy with CS diagnosed at the First Affiliated Hospital of Zhengzhou University in April 2021 was selected as the study subject. Clinical data were retrospectively analyzed. Peripheral blood samples were obtained from the child and his parents, followed by genomic DNA extraction and whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing. This study has been approved by the Medical Ethics Committee of the Hospital of Zhengzhou University (Ethics No. 2024-KY-1103-001). RESULTS: The child has manifested with seizures, microcephaly, and global developmental delay. WES revealed that he has harbored a novel de novo hemizygous nonsense variant of the SLC9A6 gene, namely c.1014G>A (p.W338*). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic. CONCLUSION The hemizygous c.1014G>A nonsense variant of the SLC9A6 gene probably underlay the pathogenesis in this child. Above discovery has expanded mutational spectrum of the SLC9A6 gene and enabled definite diagnosis of the child.
Humans ; Male ; Infant ; Microcephaly/genetics* ; Spasms, Infantile/genetics* ; Sodium-Hydrogen Exchangers/genetics* ; Exome Sequencing ; Intellectual Disability/genetics* ; Genetic Diseases, X-Linked/genetics* ; Mutation ; Seizures/genetics* ; Ataxia ; Epilepsy ; Ocular Motility Disorders

Psoriasis arthritis (PsA) is a chronic inflammatory musculoskeletal disease intricately linked to psoriasis (PsO), with a multifaceted etiology encompassing genetic, environmental, and immunological factors. Characterized by complex clinical manifestations, PsA often follows a protracted course with a propensity for relapses, potentially culminating in joint deformity and disability. The condition is further complicated by associated comorbidities such as inflammatory bowel disease, uveitis, cardiovascular disease, and metabolic syndrome, which significantly diminish patients′ quality of life. Early detection and screening of PsA are crucial for its management and prevention of adverse outcomes. However, in China, there is a notable deficiency in the recognition and early diagnosis of PsA, with missed or incorrect diagnoses being relatively common. The consensus comprises four overarching statements and sixteen detailed recommendations, with the overarching goal of enhancing the early diagnosis and treatment of PsA by clinical physicians, thereby improving patient outcomes.

Osteoarthritis (OA) is the most common degenerative joint disease. Its pathological process is related to inflammatory response, chondrocyte apoptosis, and cartilage degeneration. Hippo-yes-associate protein(YAP) signaling pathway plays an important role in mediating organ size and tissue homeostasis. In recent years, the key effector protein YAP in the Hippo-YAP pathway has become a research hotspot in osteoarthritis. This article introduces the activation process of Hippo-YAP signaling pathway and the biological role of YAP. It reviews the progress of YAP in regulating osteoarthritis by influencing the proliferation and differentiation of mesenchymal stem cells and the proliferation, differentiation, and apoptosis of articular chondrocytes. It analyzed the problems encountered in YAP research in OA, introduces the research potential of YAP in other orthopedic diseases, and provides new ideas for subsequent research in Osteoarthritis.
Osteoarthritis/metabolism* ; Humans ; Signal Transduction ; Protein Serine-Threonine Kinases/physiology* ; Hippo Signaling Pathway ; YAP-Signaling Proteins ; Adaptor Proteins, Signal Transducing/physiology* ; Animals ; Transcription Factors ; Chondrocytes/cytology* ; Cell Cycle Proteins

OBJECTIVES: To study the impact of family socioeconomic status on children's reading fluency and the chain mediation effect of family reading environment and children's living and learning styles in this relationship. METHODS: A total of 473 children from grades 2 to 6 in two primary schools in Nanjing were selected through stratified random sampling. The children's reading fluency was assessed, and a questionnaire was used to collect information on family socioeconomic status, family reading environment, and children's living and learning styles. The mediation model was established using the Process macro in SPSS, and the Bootstrap method was employed to test the significance of the mediation effects. RESULTS: Family socioeconomic status, family reading environment, and children's living and learning styles were significantly positively correlated with reading fluency (P<0.001). The family reading environment and children's living and learning styles mediated the relationship between family socioeconomic status and children's reading fluency. Specifically, the independent mediation effect of family reading environment accounted for 11.02% of the total effect, while the independent mediation effect of children's living and learning styles accounted for 10.79%. The chain mediation effect of family reading environment and children's living and learning styles accounted for 7.41% of the total effect. CONCLUSIONS Family socioeconomic status can affect children's reading fluency through three pathways: family reading environment, children's living and learning styles, and the chain mediation effect of family reading environment and children's living and learning styles.
Humans ; Child ; Male ; Female ; Reading ; Learning ; Social Class ; Family

OBJECTIVES: To investigate the effect of interferon-λ1 (IFN-λ1) on glucocorticoid (GC) resistance in human bronchial epithelial cells (HBECs) stimulated by respiratory syncytial virus (RSV). METHODS: HBECs were divided into five groups: control, dexamethasone, IFN-λ1, RSV, and RSV+IFN-λ1. CCK-8 assay was used to measure the effect of different concentrations of IFN-λ1 on the viability of HBECs, and the sensitivity of HBECs to dexamethasone was measured in each group. Quantitative real-time PCR was used to measure the mRNA expression levels of p38 mitogen-activated protein kinase (p38 MAPK), glucocorticoid receptor (GR), and MAPK phosphatase-1 (MKP-1). Western blot was used to measure the protein expression level of GR in cell nucleus and cytoplasm, and the nuclear/cytoplasmic ratio of GR was calculated. RESULTS: At 24 and 72 hours, the proliferation activity of HBECs increased with the increase in IFN-λ1 concentration in a dose- and time-dependent manner (P˂0.05). Compared with the RSV group, the RSV+IFN-λ1 group had significant reductions in the half-maximal inhibitory concentration of dexamethasone and the mRNA expression level of p38 MAPK (P<0.05), as well as significant increases in the mRNA expression levels of GR and MKP-1, the level of GR in cell nucleus and cytoplasm, and the nuclear/cytoplasmic GR ratio (P<0.05). CONCLUSIONS IFN-λ1 can inhibit the p38 MAPK pathway by upregulating MKP-1, promote the nuclear translocation of GR, and thus ameliorate GC resistance in HBECs.
Humans ; p38 Mitogen-Activated Protein Kinases/genetics* ; Glucocorticoids/pharmacology* ; Receptors, Glucocorticoid/analysis* ; Dual Specificity Phosphatase 1/physiology* ; Dexamethasone/pharmacology* ; Drug Resistance/drug effects* ; Respiratory Syncytial Viruses ; Interferons/pharmacology* ; MAP Kinase Signaling System/drug effects* ; Epithelial Cells/drug effects* ; Signal Transduction/drug effects* ; Cells, Cultured