AIM: To investigate expression differences and mechanism of action of serine/threonine kinase 1(AKT1), ATP synthase F1 subunit(ATP5F1), and Bcl-2-associated anti-apoptotic gene 3(BAG3)in the occurrence and progression of pterygium.METHODS:Pterygium-related gene expression data were retrieved from GEO database to screen differentially expressed genes(DEGs). String and Cytoscape were used to construct protein-protein interaction(PPI)networks and identify core targets. GO/KEGG enrichment analyzed mitochondrial metabolic pathways. The pterygium samples(head/body)were collected; pathological features were evaluated by HE staining, and the expression of AKT1, ATP5F1, and BAG3 was detected via immunohistochemistry(IHC).RESULTS:A total of 1 264 DEGs were identified(585 upregulated, 679 downregulated). GO analysis showed significant enrichment of mitochondrial pathways regarding to biological processes, cell components and molecular functions; KEGG analysis highlighted oxidative phosphorylation and chemical carcinogenesis-reactive oxygen species(ROS)pathways. The head and body pterygium samples were collected from 28 cases(28 eyes)that received pterygium surgery, including 7 males(7 eyes)and 21 females(21 eyes), with a mean age of 69.32±8.98 years. HE staining showed more severe dysplasia, disordered stroma, and inflammation in the pterygium head versus the body. IHC detection confirmed significantly lower AKT1, ATP5F1, and BAG3 expression in the head compared with the body(all P<0.05).CONCLUSION:GEO-based bioinformatics and experiments confirmed that AKT1/ATP5F1/BAG3(mitochondrial genes)had significant differential expression in pterygium, correlating with pathological progression. They may regulate mitochondrial metabolism to mediate pterygium progression, offering new insights for targeted therapy.

As a mature neuromodulation technique with sufficient evidence and wide application， transcranial magnetic stimulation （TMS） has become a highly promising approach for the treatment of insomnia disorder. However， there is still a lack of unified standards for formulation of treatment regimens， technical operations， indications and contraindications， treatment of adverse reactions， and application in special populations. In order to standardize the application of TMS in the diagnosis and treatment of insomnia disorder， Professional Committee of Sleep and Neuromodulation of Chinese Sleep Research Society organized the compilation of the technical specifications. This document systematically elaborates on the technical principles and stimulation modes of TMS， summarizes the clinical evidence for its application in the treatment of primary insomnia disorder and comorbid conditions such as depression and cognitive impairment， clarifies the key points for formulating treatment regimens （including stimulation coils， targets， modes， and intensity）， refines the technical specifications such as treatment room setup， personnel qualifications， operation procedures， and efficacy evaluation， and provides recommendations for the management of adverse reactions and principles for use in special populations， which provides a comprehensive expert consensus and practical guidance for the standardized clinical application of TMS in the treatment of insomnia disorder.

Objective Idiopathic rolandic epilepsy syndrome （IRES） is the most common epilepsy syndrome in childhood， and its lesion site remains undetermined. This article aims to investigate the source of epileptiform discharges in IRES using magnetoencephalography （MEG）.Methods A total of 70 patients with IRES were enrolled in this prospective MEG-based study， among whom there were 53 children with benign epilepsy of childhood with centrotemporal spikes （BECTS）， 12 children with atypical benign partial epilepsy （ABPE）， 3 children with Landau-Kleffner syndrome （LKS）， and 2 children with epileptic encephalopathy with continuous spike-and-waves during slow-wave sleep （CSWS）. Epileptiform discharges were collected independently from each patient 10 times， and an MEG source analysis was performed. Standardized low-resolution brain electromagnetic tomography was used to perform source localization of the distributed source model. The spike source density was quantified into amplitude， and source location was determined according to the Desikan-Killiany atlas. The association between the distribution of spike source in brain and clinical manifestations was analyzed.Results In IRES， there were significant differences in the source locations of epilepsy discharge between BECTS， ABPE， LKS， and CSWS. The current source density of CSWS was stronger in the frontal lobe， the temporal lobe， and the anterior cingulate gyrus， while that of ABPE was stronger in the frontal lobe， and that of BECTS and LKS were stronger in the temporal lobe. The more severe phenotype of epilepsy， such as generalized tonic-clonic seizure， was associated with a stronger current source density in the brain， which was consistent with electroencephalography manifestations.Conclusion This study identifies different sources of epileptiform discharges in IRES. The density distribution of these spike sources may help to explain the discharge， cognitive， and neuropsychological characteristics in different subtypes of IRES.
Magnetoencephalography

OBJECTIVES: To investigate the role of PTEN-induced putative kinase 1 (PINK1) in regulating the viability, migration, and apoptosis of colorectal cancer (CRC) cells, and to explore its potential epigenetic mechanisms. METHODS: PINK1 was overex-pressed or knocked down in HCT116 and DLD1 CRC cell lines using lentiviral vectors, with efficiency verified by qRT-PCR and Western blotting. Cell proliferation, colony formation, migration, and apoptosis were assessed using CCK-8, colony formation, wound healing, Transwell, and Hoechst 33258 staining assays, respectively. Protein levels of apoptosis-related and histone modification-related markers were analyzed by Western blotting. Genome-wide chromatin accessibility was profiled using ATAC-seq. RESULTS: PINK1 expression was significantly downregulated at both mRNA and protein levels in CRC tissues compared to normal tissues. PINK1 overexpression inhibited cell prolifera-tion, colony formation, and migration in HCT116 and DLD1 cells (all P<0.05), whereas PINK1 knockdown promoted these malignant phenotypes (all P<0.05). PINK1 overex-pression induced apoptosis, associated with decreased levels of anti-apoptotic proteins (Mcl-1, Bcl-2, Bcl-xl) and increased pro-apoptotic Bax (all P<0.05), without altering p53 expression. Mechanistically, PINK1 overexpression reduced the expression of histone H3 lysine 9 trimethylation (H3K9me3) and histone H3 lysine 27 trimethylation (H3K27me3), and increased the expression of histone H3 lysine 9 acetylation (H3K9ac) and histone H3 lysine 27 acetylation (H3K27ac). It also downregulated key histone-modifying enzymes, including EZH2, EZH1, SUZ12, and histone deacetylase 3 (HDAC3) (all P<0.01). ATAC-seq revealed that PINK1 overexpression increased chromatin accessibility, particularly around transcription start sites. CONCLUSIONS PINK1 acts as a tumor suppressor in colorectal cancer by inhibiting proliferation and migration, promoting apoptosis, and remodeling the epigenetic landscape through altering histone modifications and enhancing chromatin accessibility.

OBJECTIVE: To investigate the midterm clinical efficacy of medial patellofemoral complex (MPFC) reconstruction for recurrent patellar dislocation with high-grade trochlear dysplasia. METHODS: A retrospective analysis was carried out among adult patients who underwent arthroscopically assisted MPFC reconstruction between January 2014 and December 2020. Dejour classification was evaluated to grade trochlear dysplasia; tibial tubercle-trochlear groove (TT-TG) distance and Insall-Salvati index were measured. Preoperative and postoperative patient-reported outcome measures (PROMs) were compared, including International Knee Documentation Committee (IKDC) score, Kujala score, Lysholm score and Tegner score. Information regarding returning-to-sport rate, re-instability events and complications was collected. Patellar tilt (PT), lateral patellar displacement (LPD) and bisect offset (BSO) ratio were measured based on axial computed tomography before and after surgery to assess the patellofemoral congruence. RESULTS: A total of 46 MPFC reconstructions in 43 patients were enrolled, including 16 male and 27 female. Mean age at surgery was (22.2±7.6) years (range: 14-44 years). Mean follow-up was (49.9±22.6) months (range: 18-102 months). The percentages of Dejour B, C and D dysplasia were 37.0% (17/46), 43.5% (20/46), and 19.6% (9/46), respectively. Mean Insall-Salvati index was 1.2±0.2 (range: 0.85-1.44), and mean TT-TG distance was (19.6±3.5) mm (range: 10.6-28.7 mm). At latest follow-up, there were significant improvements in all PROMs (P < 0.001): IKDC score, from 56.3±15.1 to 86.2±8.1; Kujala score, from 58.9±15.6 to 92.6±5.4; Lysholm score, from 63.7±15.0 to 94.0±5.7; Tegner score, from 3.1±1.4 to 4.7±1.4, and there were no significant differences in the improvements of the scores between the patients with Dejour B, C and D dysplasia. Overall, ninety percent of the patients returned to their preoperative sports level. One patient reported a postoperative subluxation, while no cases of infection, limited range of motion or patella fracture were observed. PT, LPD and BSO ratio were all significant altered (P < 0.001) after MPFC reconstruction. CONCLUSION Arthroscopically assisted MPFC reconstruction yielded satisfactory midterm clinical results for recurrent patellar dislocation with high-grade trochlear dysplasia. No significant differences of improvements in knee function were observed among the three types of high-grade trochlear dysplasia.
Humans ; Patellar Dislocation/surgery* ; Male ; Female ; Adult ; Arthroscopy/methods* ; Retrospective Studies ; Adolescent ; Young Adult ; Patellofemoral Joint/surgery* ; Recurrence ; Plastic Surgery Procedures/methods* ; Patella/surgery* ; Treatment Outcome

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective:To investigate the distribution and clinical significance of amniotic fluid karyotype results in 2 725 cases from southern Anhui.Methods:The karyotypes of amniotic fluid from 2 725 cases of second-trimester pregnant women treated in our hospital from Jan 2017 to Dec 2023 were collected.The annual abnormal detection rate and overall abnormal rate were analyzed.Meanwhile,the abnormal detection rate was compared among 8 groups of different clinical indication including adverse pregnancy history,advanced maternal age(≥35 years),high risk of Down syndrome screening,high risk of non-invasive prenatal testing(NIPT),nuchal translucency thickness(NT)≥2.5 mm,abnormal ultrasound findings,two or more concurrent positive indications,and others.The abnormal detection rate was calculated within high risk of Down syndrome screening and NIPT.Results:Significant differences in annual abnormal rates were observed from 2017 to 2023(χ2=19.705,P=0.003).Among 2 725 cases,233(8.55%)showed abnormal karyotypes.Among them,abnormal autosomal number was the most prevalent(4.41%,120/2 725),with inversion being the most common chromosome structural abnormality.Significant differences in abnormal rates were noted among the eight clinical indication groups(χ2=438.516,P＜0.01).No statistical difference was found in abnormal detection rates among the three high-risk subgroups of Down syndrome screening(χ2=0.323,P=0.851),while significant differences were observed within the high-risk subgroups of NIPT(χ2=100.901,P＜0.01).Polymorphisms were detected in 65 cases(2.38%).Conclusions:Chromosomal numerical and structural abnormalities have been detected in southern Anhui over the past seven years,with variations across subgroups.Karyotype analysis effectively detects second-trimester fetal chromosomal abnormalities,aiding in the prevention of birth defects and worthing clinical application.

Gastric cancer is a malignant tumor of the digestive system with strong invasiveness and a high metastasis rate.Its morbidity and mortality rank among the top five in the world and the prognosis is closely related to the disease stage.Multidisciplinary comprehensive treatment based on systemic antitumor drugs is generally adopted in patients with advanced or metastatic gastric can-cer,but the prognosis is typically poor.With the in-depth research on the tumor microenvironment,the development of multi-omics technology,and the application of immunotherapy and neoadjuvant chemoradiotherapy,the therapeutic effect of advanced gastric can-cer has been initially improved,and immunotherapy has become the most potential of the treatment strategies.Many studies have found that Helicobacter pylori(Hp)infection status is closely related to the efficacy of immunotherapy for gastric cancer,especially im-mune checkpoint inhibitors(ICIs),but there is not clear whether it has advantages or disadvantages.This article reviews the current research on the efficacy of Hp on ICIs in advanced gastric cancer to provide ideas for further research on the interaction between Hp in-fection and tumor immunotherapy.

Objective To investigate the protective effects and possible mechanisms of sofalcone on small intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs(NSAIDs)in rats.Methods In the first group of animal experiments,rats were randomly divided into five groups:normal control group,diclofenac group(diclofenac 7.5 mg·kg-1),and sofalcone high-doses groups(sofalcone 10 mg·kg-1+diclofenac 7.5 mg·kg-1),sofalcone medium-doses groups(sofalcone 5 mg·kg-1+diclofenac 7.5 mg·kg-1),and sofalcone low-doses groups(sofalcone 2 mg·kg-1+diclofenac 7.5 mg·kg-1).Each group received daily gavage for seven days.Serum D-lactate levels were measured,and histological damage to the small intestine was assessed through HE staining and pathological scoring.In the second group,rats were separated into three groups:normal control group,diclofenac group(diclofenac 7.5 mg·kg-1),and sofalcone group(sofalcone 2 mg·kg-1+diclofenac 7.5 mg·kg-1).Concurrently,the rats'body mass,24-hour diet,and water intake were monitored.Additionally,serum levels of pro-inflammatory cytokines such as IL-6,IFN-γ,TNF-α,inflammatory markers CRP and D-lactate,as well as measurements of tissue reactive oxygen species(ROS),lactate dehydrogenase(LDH),and mitochondrial membrane potential were conducted using appropriate kits.Western blotting was applied to assess the expression levels of intercellular junction proteins(Occludin,Claudin-1,α-Catenin),programmed necrosis pathway-associated proteins including receptor-interacting protein kinase 1(RIPK1),RIPK3,and mixed lineage kinase domain-like pseudokinase(MLKL)along with p-MLKL.Results In the first experiment,the diclofenac group exhibited significant histological damage to the small intestine,with elevated levels of D-lactic acid and pathological scores compared to the normal control group(P<0.01).Following intervention with sofalcone,both the histological damage and the levels of D-lactic acid and pathological scores in the small intestine were notably reduced(P<0.05 or P<0.01).However,there was no substantial difference in pathological scores among different doses of sofaclone groups(P>0.05).In the second experiment,compared with normal control group,rats in the diclofenac group showed decreased body mass,24-hour average diet and water intake,along with elevated levels of IL-6,IFN-γ,TNF-α,CRP,D-lactic acid,tissue ROS,LDH activity,RIPK1,RIPK3,and p-MLKL/MLKL protein expression levels,as well as mitochondrial membrane potential(P<0.05 or P<0.01).Moreover,Occludin,Claudin-1,and α-Catenin protein expression levels were reduced(P<0.05 or P<0.01).Following sofalcone intervention,the previously mentioned parameters were reversed(P<0.05 or P<0.01).Notably,there was no statistically significant difference observed in the reduction of RIPK1 protein expression(P>0.05).Conclusions Sofalcone reduces NSAID-induced small intestinal mucosal injury in rats by inhibiting the RIPK1/RIPK3/MLKL-dependent programmed necrosis pathway.

BACKGROUND:Cannabidiol has anti-inflammatory,antioxidant,and other pharmacological effects,and has no mental activity,so the research in liver disease is increasing day by day,but its effect on transforming growth factor-β1/Smad signal transduction pathway in hepatic stellate cells is not clear.OBJECTIVE:To investigate the effect of cannabidiol on transforming growth factor-β1/Smad signal transduction pathway in hepatic stellate cells and its possible mechanism of anti-hepatic fibrosis.METHODS:(1)In vitro experiment:Rat hepatic stellate cell line(HSC-T6)was selected and cultured in six groups.The control group was routinely cultured for 24 hours.The simple drug group was cultured with cannabidiol for 24 hours.The modeling group was cultured with transforming growth factor β1 for 24 hours.The modeling+low-dose drug group,the modeling+high-dose drug group,and the modeling+positive control group were cultured with transforming growth factor β1 for 24 hours,1,5 μmol/L cannabidiol and silymarin were cultured for 24 hours.After culture,the mRNA expression of α-smooth muscle actin and type Ⅰ collagen,the levels of interleukin 1β and tumor necrosis factor α,and the protein expression of type Ⅰ collagen and transforming growth factor β1/Smad signal transduction pathway were detected in each group.(2)In vivo experiments:C57BL/6J mice were randomly divided into five groups with eight mice in each group.Models were not established in the sham operation group.The liver fibrosis models were established by biliary ligation in the modeling group,the modeling+low-dose drug group,the modeling+high-dose drug group,and the modeling+positive control group.At 3 weeks after the modeling,4,8 mg/kg cannabidiol or silymarin were injected intraperitoneally,once a day,for 7 consecutive days.After administration,the liver function,liver pathological morphology,expression levels of α-smooth muscle actin,type Ⅰ collagen,and transforming growth factor β1/Smad signal transduction pathway related protein were detected in each group.RESULTS AND CONCLUSION:(1)In vitro experiment:Compared with the control group,mRNA expression of α-smooth muscle actin and type Ⅰ collagen,interleukin 1β and tumor necrosis factor α,and protein expression of type Ⅰ collagen,transforming growth factor β1 and p-Smad2/3 in HSC-T6 cells were increased(P<0.05),while Smad7 protein expression was decreased(P<0.05)in the modeling group.Two doses of cannabidiol could improve the above changes in HSC-T6 cells induced by transforming growth factor β1,and the improvement was more obvious in the modeling+high-dose drug group.(2)In vivo experiment:Compared with sham operation group,the activities of serum alanine aminotransferase and aspartate aminotransferase were increased(P<0.05),inflammatory cell infiltration and collagen content in liver tissue were increased(P<0.05),and the transforming growth factor β1/Smad signal transduction pathway was activated;α-smooth muscle actin and type Ⅰ collagen expression levels were increased(P<0.05)in the modeling group.Two doses of cannabidiol could reduce the changes of the above indexes in the modeling mice,and the effect was more obvious in the modeling+high-dose drug group.(3)It is indicated that cannabidiol inhibits hepatic fibrosis by suppressing the activation of transforming growth factor-β1/Smad signal transduction pathway in hepatic stellate cells.