ObjectiveTo explore the function and related molecular mechanisms of magnoflorine against colon cancer via network pharmacology， molecular docking， and in vitro cell experiments. MethodsIn this study， the canonical SMILES of magnoflorine was obtained from the PubChem database， and the potential targets of magnoflorine were predicted by the Swiss Target Prediction database， while the disease targets of colon cancer were obtained from the DisGeNET， GeneCards and OMIM databases. The intersecting targets between magnoflorine's predicted targets and colon cancer disease targets were taken， and a protein-protein interaction （PPI） network was constructed and analyzed. The DAVID online database was employed to conduct Gene Ontology （GO） and KEGG pathway enrichment analyses on core targets. The top five key targets screened were docked with magnoflorine using AutoDock software. Finally， cellular experiments including CCK-8 assays， EdU experiments， cell scratch assays， and Transwell assays were conducted to validate the results from network pharmacology and molecular docking. Results44 key targets of magnoflorine in resisting colon cancer were acquired. The molecular docking results showed that magnoflorine had a strong binding activity with the core target signal transducer and activator of transcription 3 （STAT3） in the top five of the PPI network. Cellular experiments confirmed that magnoflorine could inhibit the proliferation and migration of colon cancer cells by suppressing the JAK/STAT3 signaling pathway. ConclusionMagnoflorine may inhibit the proliferation and migration of colon cancer cells by regulating the JAK/STAT3 signaling pathway.

Positional information plays a crucial role in embryonic pattern formation, yet its role in tooth development remains unexplored. In this study, we investigated the regional specification of lingual and buccal dental mesenchyme during tooth development. Tooth germs at the cap stage were dissected from mouse mandibles, and their lingual and buccal mesenchymal regions were separated for bulk RNA sequencing. Gene ontology analysis revealed that odontogenesis, pattern specification, and proliferation-related genes were enriched in the lingual mesenchyme, whereas stem cell development, mesenchymal differentiation, neural crest differentiation, and regeneration-related genes were predominant in the buccal mesenchyme. Reaggregation experiments using Wnt1^creERT/+; R26R^tdT/+ and WT mouse models demonstrated that lingual mesenchyme contributes to tooth formation, while buccal mesenchyme primarily supports surrounding tissues. Furthermore, only the lingual part of tooth germs exhibited odontogenic potential when cultured in vitro and transplanted under the kidney capsule. Bulk RNA transcriptomic analysis further validated the regional specification of the lingual and buccal mesenchyme. These findings provide novel insights into the molecular basis of positional information in tooth development and pattern formation.
Animals ; Mice ; Odontogenesis/genetics* ; Tooth Germ/cytology* ; Mesoderm/cytology* ; Cell Differentiation ; Mesenchymal Stem Cells ; Tooth/embryology*

In recent years,there has been a significant rise in the incidence of peripheral nerve injury(PNI),highlighting the urgent need for effective treatment strategies.The inflammation and pain hypersensitivity associated with PNI greatly diminish patients'quality of life.Although there are promising treatment approaches for nerve injury,the com-plex pathological mechanisms underlying neuropathic pain caused by PNI present significant challenges for clinical manage-ment.Extensive research has established that the development of neuropathic pain is closely linked to nerve conduction and related signaling molecules.Among these,P2X4 receptor(P2X4R),an ATP-dependent ion channel,is involved in nerve signal transmission and associated pathways-plays a crucial role in the progression of neuropathic pain.This article offers a comprehensive overview of the function and distribution of P2X4R,investigates its pathological mechanisms in PNI-induced neuropathic pain,and elucidates its relationship with peripheral neuropathic pain disorders.Through this explo-ration,we aim to provide valuable insights that could inform the development of novel clinical strategies for pain management.

Objective To evaluate the sensitivity,repeatability,anti-degradation ability,in vivo temporal stability,and tissue specificity of the DNA methylation sequencing panel constructed in our previous study for height inference,so as to provide a reference for forensic application.Methods Sensitivity:different initial template quantities(50 ng,40 ng,30 ng,20 ng)were set for sequencing.Repeatability:DNA from the same sample was sequenced three times.Anti-degradation ability:whole blood was used to make blood stains,and DNA was extracted and sequenced at 0,3,6 and 9 months,respectively.In vivo temporal stability:the blood was collected at 0,3,6,and 9 months for sequencing.Tissue specificities:published data and findings were used to analyze the tissue specificities of CpGs in the panel.Results The sensitivity test showed that the initial template quantities of 20 ng detected all the CpG sites and still obtained accurate prediction results.The results of the three repeated predictions of the same sample are stable,and the differences are mainly due to the randomness of the DNN model,indicating good detection repeatability.A complete methylation profile was obtained for the blood stains left at room temperature for 9 months,and the predicted results showed a small range of fluctuations.The three samples were predicted to fluctuate within a range of 1.5 cm or less over nine months.Tissue-specific analyses showed a high correlation between blood and saliva,but can not apply to other tissues.Conclusion The DNA methylation detection system we developed in our previous study has good sensitivity,repeatability,anti degradation ability,in vivo time stability,as well as strong tissue specificity,making it suitable for height inference of blood samples.This supports the feasibility of using targeted DNA methylation analysis on whole blood samples to infer height in the field of forensic science.

BACKGROUND:Paraspinal muscle degeneration is one of the main causative factors of low back pain,and the changes in the paraspinal muscles are closely related to its occurrence and development.At present,clinical practitioners focus on the changes of paraspinal muscles in degenerative lumbar diseases to prevent and treat lumbar diseases,but ignore the connection and related mechanisms between lumbar intervertebral disc degeneration and paraspinal muscles.OBJECTIVE:To comprehensively summarize the interaction between paraspinal muscles and lumbar intervertebral discs,and to review the relationship and mechanisms between lumbar intervertebral disc degeneration and paraspinal muscles,in order to provide a reference for clinical prevention and treatment.METHODS:Chinese keywords"lumbar intervertebral disc,paraspinal muscle,multifidus muscle,low back pain,degeneration,imaging,magnetic resonance imaging"were used to search the relevant literature in Chinese databases such as CNKI,VIP,and WanFang.English keywords"lumbar disc,paraspinal muscle,multifidus muscle,low back pain,degeneration,imaging,MRI"were used to search the relevant literature in databases such as Medline,PubMed,and Web of Science.After preliminary screening of titles and abstracts,68 articles were finally selected for result analysis according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Researchers have used various methods to evaluate the degree of paraspinal muscle degeneration,and at the same time evaluated the degree of lumbar intervertebral disc degeneration according to the Pfirrmann grading system.It is found that clinical diagnosis and treatment should pay attention to gender differences,and the influence of factors such as obesity on the degeneration of intervertebral discs and muscles,in order to develop more individualized treatment plans.(2)There is a certain correlation between lumbar intervertebral disc degeneration and paraspinal muscle fat infiltration,but the research results are controversial.Most studies have found that fat infiltration of the paraspinal muscles(especially the multifidus muscle)is positively correlated with the degree of lumbar intervertebral disc degeneration.(3)It is currently believed that the three mechanisms of disuse atrophy,denervation,and inflammatory factors may interact with each other to jointly lead to structural and functional changes in the paraspinal muscles,which are closely related to the occurrence of lumbar intervertebral disc degeneration and low back pain.(4)Clinically,attention should be paid to the changes of the muscles at the level below the affected nerve root segment,which is helpful for the diagnosis and localization of lumbar radiculopathy.At the same time,inhibition of inflammatory factors may become a potential target for treatment.(5)Clinically,the first step is to correct nerve root compression through appropriate medication or surgery to control inflammatory reactions and nerve root pain,and then carry out targeted muscle rehabilitation training.If necessary,consider using new treatment methods such as interferential current electrical stimulation to improve the patient's symptoms and prognosis.

OBJECTIVE: To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. METHODS: The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). RESULTS: Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a "cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. CONCLUSION The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.
Humans ; Male ; Female ; Child, Preschool ; Infant ; Child ; Olivopontocerebellar Atrophies/genetics* ; Arginine-tRNA Ligase/genetics* ; Mutation ; Cerebellar Diseases

Objective To investigate the capacity of low-intensity pulsed ultrasound(LIPUS)for promoting osteogenic differentiation of senescent bone marrow mesenchymal stem cell(BMMSC)in mice,also the potential mechanism of involving myocardin-related transcription factor-A(MRTF-A)during this process.Methods Five aged mice received LIPUS irradiation on the left femur for eight weeks.Micro CT and HE staining were employed to evaluate bone status of bilateral femur.Bone marrow cells were isolated from mouse long bones,BMMSC were cultured,and the cells were divided into H2O2+LIPUS group,H2O2 group and control group.Mouse BMMSC were subjected to H2O2 for 3 days,followed by reactive oxygen species fluorescence staining and senescence-associated β-galactosidase staining to assess cellular senescence.Immunofluorescence and phalloidin staining were performed to examine MRTF-A distribution and cytoskeletal status.Based on H2O2-induced senescence model,MRTF-A nuclear translocation inhibitor CCG-100602 was applied,and the cells were further divided into H2O2+CCG-100602+LIPUS group,H2O2+CCG-100602 group,H2O2+LIPUS group and H2O2 group.Immunofluorescence staining was used to assess MRTF-A distribution.Alkaline phosphatase(ALP)and alizarin red staining were conducted to evaluate osteogenic differentiation capacity.Results LIPUS resulted in increased trabecular bone in the left femur of aged mice compared to the right femur,with increased bone volume to total volume and trabecular number and decreased trabecular spacing(both P＜0.05).Compared with H2O2 group,H2O2+LIPUS group showed increased nuclear expression of MRTF-A and increased intracellular rigid actin filament density.The nuclear expression of MRTF-A in H2O2+CCG-100602+LIPUS group was significantly lower than that in H2O2+LIPUS group.Compared with the H2O2+CCG-100602+LIPUS group and H2O2 group,the ALP and alizarin red staining positive areas in H2O2+LIPUS group were significantly larger.Conclusion LIPUS could improve osteoporosis in aged mice.Nuclear translocation of MRTF-A was a key regulator to LIPUS for promoting osteogenic differentiation of senescent BMMSC.

Objective:To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. Methods:The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). Results:Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a " cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. Conclusion:The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.

BACKGROUND:Paraspinal muscle degeneration is one of the main causative factors of low back pain,and the changes in the paraspinal muscles are closely related to its occurrence and development.At present,clinical practitioners focus on the changes of paraspinal muscles in degenerative lumbar diseases to prevent and treat lumbar diseases,but ignore the connection and related mechanisms between lumbar intervertebral disc degeneration and paraspinal muscles.OBJECTIVE:To comprehensively summarize the interaction between paraspinal muscles and lumbar intervertebral discs,and to review the relationship and mechanisms between lumbar intervertebral disc degeneration and paraspinal muscles,in order to provide a reference for clinical prevention and treatment.METHODS:Chinese keywords"lumbar intervertebral disc,paraspinal muscle,multifidus muscle,low back pain,degeneration,imaging,magnetic resonance imaging"were used to search the relevant literature in Chinese databases such as CNKI,VIP,and WanFang.English keywords"lumbar disc,paraspinal muscle,multifidus muscle,low back pain,degeneration,imaging,MRI"were used to search the relevant literature in databases such as Medline,PubMed,and Web of Science.After preliminary screening of titles and abstracts,68 articles were finally selected for result analysis according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Researchers have used various methods to evaluate the degree of paraspinal muscle degeneration,and at the same time evaluated the degree of lumbar intervertebral disc degeneration according to the Pfirrmann grading system.It is found that clinical diagnosis and treatment should pay attention to gender differences,and the influence of factors such as obesity on the degeneration of intervertebral discs and muscles,in order to develop more individualized treatment plans.(2)There is a certain correlation between lumbar intervertebral disc degeneration and paraspinal muscle fat infiltration,but the research results are controversial.Most studies have found that fat infiltration of the paraspinal muscles(especially the multifidus muscle)is positively correlated with the degree of lumbar intervertebral disc degeneration.(3)It is currently believed that the three mechanisms of disuse atrophy,denervation,and inflammatory factors may interact with each other to jointly lead to structural and functional changes in the paraspinal muscles,which are closely related to the occurrence of lumbar intervertebral disc degeneration and low back pain.(4)Clinically,attention should be paid to the changes of the muscles at the level below the affected nerve root segment,which is helpful for the diagnosis and localization of lumbar radiculopathy.At the same time,inhibition of inflammatory factors may become a potential target for treatment.(5)Clinically,the first step is to correct nerve root compression through appropriate medication or surgery to control inflammatory reactions and nerve root pain,and then carry out targeted muscle rehabilitation training.If necessary,consider using new treatment methods such as interferential current electrical stimulation to improve the patient's symptoms and prognosis.