ObjectiveTo investigate the effects of 7-dehydrocholesterol reductase （DHCR7） in promoting proliferation， migration， and invasion of lung adenocarcinoma cells and the underlying signaling mechanisms. MethodsThe expression level of DHCR7 in lung adenocarcinoma and its prognosis were analyzed by using public databases. DHCR7 protein expression levels in the lung adenocarcinoma cell lines H1299 and A549 were assessed by Western blot， using the normal lung epithelial cell line BEAS-2B as a control. Small interfering RNA （siRNA） was used to knock down DHCR7 expression in H1299 and A549 cells. Assays including colony formation， CCK-8， wound healing， and Transwell experiments were conducted to assess the proliferation， migration， and invasion of the knockdown cells. Next， Western blot was employed to assess the phosphorylation levels of key signaling molecules in the phosphoinositide 3-kinase/protein kinase B （PI3K/AKT）， janus kinase/signal transducer and activator of transcription 3 （JAK/STAT3），mitogen-activated protein kinase/extracellular signal-regulated kinase pathway （MAPK/ERK） （p-AKT， p-STAT3， p-ERK）. ResultsBioinformatics results indicated that both DHCR7 mRNA and protein were highly expressed in lung adenocarcinoma compared with normal tissues adjacent to cancer. Furthermore， higher DHCR7 mRNA level was associated with poor prognosis （P<0.001）. The expression levels of DHCR7 were significantly higher in both H1299 and A549 cells than that in BEAS-2B cells （P<0.05， P<0.01）. Compared with si-control， the proliferation， migration， and invasion abilities of si-DHCR7 H1299 and A549 cells significantly decreased. Among the phosphorylated signaling molecules detected， p-ERK was significantly downregulated （P<0.000 1， P<0.01） whereas p-AKT and p-STAT3 levels were not significantly changed. ConclusionDHCR7 has prominent effects in promoting the proliferation， migration， and invasion of lung adenocarcinoma cells， and the underlying mechanisms are related to the MAPK/ERK signaling pathway.

Objective: To investigate the associations between 24 hour activity and the quality of life (QoL) in children with autism spectrum disorder (ASD), and to explore their isotemporal substitution effects, providing a reference for developing intervention strategies of their QoL. Methods: From March to June 2025, 288 children with ASD from 7 special education schools in Jinan were selected by using a cluster random sampling method. The 24 hour activity was measured by using ActiGraph wGT3X-BT triaxial accelerometers, and their QoL was assessed by applying a parent proxy Pediatric Quality of Life Inventory. Multiple linear regression was employed to analyze the associations between 24 hour activity and QoL in children with ASD. Isotemporal substitution analysis was applied to analyze the dose response relationship of 24 hour activity time and the QoL scores in children with ASD. Results: Within the 24 hour activities of children with ASD, the daily time spent in sleep, sedentary behavior (SB), light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were 610.49，605.80，195.49，28.22 minutes, respectively. Multiple linear regression analysis showed that, after controlling for confounding factors such as gender, age, and parental education level, the proportion of time spent in MVPA was positively associated with QoL scores ( β =1.75) in children with ASD, whereas the proportion of time spent in SB was negatively associated with QoL scores ( β =-1.00)(both P <0.01). In the dose response relationship, reallocating time from sleep, SB, and LPA to MVPA was associated with an improvement in QoL in children with ASD, with increased scores of 1.38, 1.55, 1.47, respectively; conversely, the reverse substitution was associated with a decline in QoL, and the scores decreased by 2.31, 2.99 and 2.68, respectively, with the latter demonstrating a more pronounced effect(all P <0.05). Conclusions Enhancing the QoL for children with ASD should be grounded in the overall balance of 24 hour activity. Time reallocation strategies should be implemented with an emphasis on relatively increasing MVPA and reducing SB.

ObjectiveTo investigate the biological reparative effects of platelet-rich fibrin （PRF） extract on injured endometrial stromal cells （ESCs） induced by mifepristone and the underlying molecular mechanisms. MethodsAn ESCs injury model was established using mifepristone treatment. Cells were divided into four groups： untreated control （Con）， mifepristone-injured group （M）， mifepristone treatment+PRF extract group （M+P）， and mifepristone treatment+PRF extract+growth factor inhibitors treatment group， including M+P+T， M+P+Me， and M+P+CJ. Cell viability was detected using the CCK-8 assay， and migration ability was evaluated via the scratch wound healing assay. The release kinetics of growth factors， including vascular endothelial growth factor （VEGF）， platelet-derived growth factor-BB （PDGF-BB）， and transforming growth factor-beta 1 （TGF-β1） from PRF extract were measured by ELISA. The mRNA and protein expression levels of apoptosis-related factors （Bcl-2， Bax， and Caspase-3） were analyzed by RT-qPCR and Western blot， respectively. ResultsVEGF， PDGF-BB， and TGF-β1 were continuously released from the PRF extract over two weeks， with peak release observed on days 3-7. The extract significantly restored the proliferation and migration of mifepristone-injured ESCs （all P<0.000 1）. PRF extract up-regulated the mRNA and protein expression of the anti-apoptotic factor Bcl-2 （all P<0.000 1） and down-regulated that of the pro-apoptotic factors Bax and Caspase-3 （all P<0.000 1） in mifepristone-injured ESCs. Inhibitors of VEGF， PDGF-BB， and TGF-β1 （Tanshinone IIA， Methylnissolin， and CJJ300） significantly reversed the protective effects of PRF extract on mifepristone-injured ESCs （all P<0.05）. ConclusionPRF extract promotes the repair of injured ESCs by enhancing cell proliferation， attenuating apoptosis， and increasing migration capacity， which involve multiple growth factors， including VEGF， PDGF-BB， and TGF-β1.

Metabolic dysfunction-associated fatty liver disease is a common chronic liver disease worldwide， and its incidence rate continues to rise. The traditional “two-hit” theory has gradually been replaced by the “multiple-hit” hypothesis， which emphasizes the synergistic effect of multiple pathogenic factors. Necroptosis is an inflammatory form of death with both the morphological characteristics of necrosis and the signaling mechanism of apoptosis， and the core of necroptosis lies in the receptor-interacting protein kinase 1-receptor-interacting protein kinase 3-mixed lineage kinase domain-like pseudokinase signaling axis. This pathway directly leads to the death of hepatocytes， and it triggers an inflammatory response and promotes the fibrosis process by releasing damage-associated molecular patterns； the pathway is also closely associated with the metabolic reprogramming of the liver. This review summarizes the activation mechanism of necroptosis in metabolic dysfunction-associated fatty liver disease， analyzes its effect on liver inflammation， fibrosis， and metabolism， and explores its therapeutic strategies and application prospects.

OBJECTIVE: To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province. METHODS: A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Ethics Number: 2019 Medical Ethics Review No. 67). RESULTS: Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c.1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c.467G>A (p.Gly156Asp) and c.1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c.1297G>C (p.Ala433Pro) and c.1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. CONCLUSION The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c.1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.
Humans ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Objective:To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province.Methods:A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Approval Number: 2019 Medical Ethics Review No. 67). Results:Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c. 1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c. 467G>A (p.Gly156Asp) and c. 1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c. 1297G>C (p.Ala433Pro) and c. 1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and may affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. Conclusion:The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c. 1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.

Objective:To synthesize a hydrolysis-resistant urushiol-modified monomer(UMM)to improve the hydrolysis resistance of light-cured composite resin,while reducing the volume shrinkage rate(VS),increasing the double bond conversion rate(DC),and mitigating the potential biosafety concerns of bisphenol A glycidyl methacrylate(Bis-GMA)monomer.Methods:UMM was synthesized by modifying urushiol via an acyl chloride reaction,and its structure was analyzed and characterized using Fourier transform infrared spectroscopy(FT-IR).Control group was consisted of Bis-GMA/triethylene glycol dimethacrylate(TEGDMA)without UMM,while 10%UMM,15%UMM,and 20%UMM groups were prepared by partially replacing Bis-GMA with UMM at mass fractions of 10%,15%,and 20%,respectively.The viscosity of UMM was measured using a rheometer.The DC of light-cured composite resin in various groups was detected by FT-IR spectroscopy,and the VS was calculated.The contact angle of light-cured composite resin in various groups was measured using the sessile drop method,and the water sorption and solubility values were calculated.The mechanical properties of light-cured composite resin in various groups were tested.The in vitro cytotoxicity of light-cured composite resin in various groups was evaluated using the cell counting kit-8(CCK-8)assay.Results:The FT-IR spectra results showed that the absorption peak of the hydroxyl group at 3 402 cm-1 disappeared,while characteristic absorption peaks of-C=O and-C=C appeared at 1 745 and 1 637 cm-1,indicating that urushiol successfully reacted with acryloyl chloride to form UMM.The viscosity of UMM ranged from 25.14 to 29.43 Pa·s.Compared with control group,the DC of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups was significantly increased(P<0.05),while the VS was significantly decreased(P<0.05),both in a dose-dependent manner.Compared with control group,the contact angle of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups was significantly increased(P<0.05).Compared with 10%UMM group,the contact angle of light-cured composite resin in 15%UMM and 20%UMM groups was further increased(P<0.05).Compared with control group,the water sorption and solubility values of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups were significantly decreased(P<0.05),showing a dose-dependent trend.After 24 h of water immersion,compared with control group,the flexural strength(FS)and elastic modulus(EM)of light-cured composite resin in 10%UMM,15%UMM,and 20%UMM groups were significantly decreased(P<0.05),also in a dose-dependent manner.After 7 d of water immersion,compared with control group,the FS of light-cured composite resin in 10%UMM group was significantly increased(P<0.05),while that in 20%UMM group was significantly decreased(P<0.05).Compared with 10%UMM group,the FS of light-cured composite resin in 15%UMM and 20%UMM groups was significantly decreased(P<0.05),exhibiting a dose-dependent trend.Compared with control group,the EM of light-cured composite resin in 15%UMM and 20%UMM groups was significantly decreased(P<0.05),also in a dose-dependent manner.The relative growth rate(RGR)of the L929 cells in control,10%UMM,15%UMM,and 20%UMM groups was above 90%,with no statistically significant differences among groups(P>0.05),and all cytotoxicity results were qualified.Conclusion:A novel low-viscosity monomer UMM is successfully synthesized in this study.All UMM-containing light-cured composite resin formulations exhibit higher DC,lower VS,reduced water sorption and solubility values,improved hydrolysis resistance,and low cytotoxicity.UMM can serve as a potential resin monomer to enhance the hydrolysis resistance of light-cured composite resin.

OBJECTIVES: To investigate the regulatory effects of Aurora-A in regulating proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells and the role of actin-related protein 2/3 complex subunit 4 (ARPC4) in mediating its effects. METHODS: The plasmids pCDH-NC, pCDH-Aurora-A, and shRNA-ARPC4 were used for inducing Aurora-A overexpression or ARPC4 knockdown in HeLa cells. The cells were divided into vector group, Aurora-A overexpression group, Aurora-A overexpression+ARPC4 knockdown group, and Aurora-A overexpression+NF‑κBp65 inhibitor group and transfected with the corresponding plasmids. The proliferation, colony-forming ability, migration and invasion of the treated Hela cells was evaluated using EdU immunofluorescence assay, crystal violet staining, scratch assay, Transwell assay, and Matrigel assay. Western blotting was performed to detect the changes in cellular expressions of EMT-related proteins and expression levels of NF-κBp65 and ARPC4. RESULTS: The expression of ARPC4 was significantly decreased in HeLa cells with Aurora-A knockdown and increased in Aurora-A-overexpressing cells. Aurora-A overexpression obviously promoted proliferation, migration, and invasion abilities of HeLa cells, and these effects was significantly antagonized by ARPC4 knockdown. In Aurora-A-overexpressing cells, the phosphorylation level of NF-κBp65 and the expression level of ARPC4 were increased significantly, and application of the NF‑κBp65 inhibitor obviously lowered the expression level of ARPC4. CONCLUSIONS Aurora-A overexpression upregulates the expression of ARPC4 by activating the NF-κBp65 signaling pathway, thereby promoting migration, invasion and EMT of HeLa cells.
Humans ; Uterine Cervical Neoplasms/metabolism* ; Female ; HeLa Cells ; Epithelial-Mesenchymal Transition ; Signal Transduction ; Cell Movement ; Neoplasm Invasiveness ; Cell Proliferation ; Aurora Kinase A/metabolism* ; Transcription Factor RelA/metabolism* ; Neoplasm Metastasis