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.

ObjectiveTo analyze the effects of the progestin-primed ovarian stimulation （PPOS） protocol on embryo euploidy rate and clinical pregnancy outcomes in infertile patients. MethodsWomen who underwent Preimplantation genetic testing for aneuploidy （PGT-A） cycles were selected as study participants （a total of 656 cycles and 3 081 blastocysts）. Participants were divided into two age groups （≤35 years and >35 years） and further stratified by ovarian stimulation protocol： the Progestin-Primed Ovarian Stimulation （PPOS） group （n=48 and 60， respectively）， the Luteal Phase Long Protocol （LP） group （n=160 and 57， respectively）， and the Gonadotropin-Releasing Hormone Antagonist Protocol （AP） group （n=220 and 111， respectively）. Baseline characteristics， ovarian stimulation outcomes， and embryo development parameters were compared among the three protocols within each age group. Additionally， clinical pregnancy outcomes of the first frozen embryo transfer （FET） cycle were compared. The primary outcome measure was the embryo euploidy rate. Results① In the ≤35 years age group， baseline follicle-stimulating hormone （bFSH） levels were significantly higher in the PPOS group compared to the LP and AP groups， and the bFSH/bLH ratio was significantly higher in the PPOS group than in the AP group （P < 0.05）. In the >35 years age group， bFSH levels in both the PPOS and AP groups were significantly higher than in the LP group （P < 0.05）.② In the ≤35 years group， there were no significant differences in the rates of metaphase II （MII） oocytes， 2-pronuclei （2 PN） zygotes， cleavage， 2 PN cleavage， blastocyst formation， high-quality embryos， or embryo euploidy between the PPOS group and either the LP or AP groups. However， the PPOS group showed significantly lower values for the following parameters compared to the other two groups： total oocytes retrieved， number of MII oocytes， number of 2 PN zygotes， number of cleaved embryos， number of 2 PN cleaved embryos， number of blastocysts formed， number of high-quality embryos， number of high-grade blastocysts， number of transferable embryos， number of cryopreserved embryos， number of biopsied blastocysts， number of euploid embryos， and the rate of obtaining at least one euploid embryo. In the >35 years group， no significant differences were observed among the PPOS， LP， and AP groups in the rates of MII oocytes， 2 PN cleavage， blastocyst formation， or in the number of euploid embryos， euploidy rate， and the rate of obtaining at least one euploid embryo. However， the PPOS group had significantly lower numbers of total oocytes retrieved， MII oocytes， 2 PN zygotes， cleaved embryos， 2 PN cleaved embryos， blastocysts formed， transferable embryos， and cryopreserved embryos compared to the LP group （P<0.05）. The high-quality embryo rate was significantly lower in the PPOS group than in the AP group （P<0.05）. The numbers of high-quality embryos， high-grade blastocysts， and biopsied blastocysts were significantly lower in the PPOS group than in both the LP and AP groups （P<0.05）. Notably， the 2 PN fertilization rate was significantly higher in the PPOS group than in the AP group， and the cleavage rate was significantly higher in the PPOS group than in both the LP and AP groups （P<0.05）.③ No significant differences were found among the three groups in the biochemical pregnancy rate， clinical pregnancy rate， live birth rate， early miscarriage rate， and late miscarriage rate following the first FET cycle. ConclusionCompared to the other two protocols， the PPOS protocol does not significantly affect embryo euploidy or clinical pregnancy rates. However， in freeze-all cycles with PGT-A， the PPOS protocol does not reduce the rate of chromosomally normal embryos but may decrease the total number of available embryos. It may not be the optimal choice for younger women， but it can be considered as a viable option for women of advanced maternal age.

Objective To investigate the clinicopathological characteristics, diagnostic key points, and treatment strategies of penile metastatic extramedullary plasmacytoma(EMP). Case Report A 47-year-old male patient presented with a painless indurated nodule on the dorsal side of the penis and had a previous history of plasmacytoma in the nasal cavity and tibia. He subsequently underwent complete excision of the penile lesion. Postoperative histopathological examination confirmed the diagnosis of anaplastic plasmacytoma. Immunohistochemical analysis showed positive staining of CD138, CD38, MUM1, and CD79a, with Ki-67(+60%). Light chain restriction was also identified. No local recurrence or distant metastasis was observed during the 5-month follow-up. Conclusion Metastatic EMP of the penis is an extremely rare condition, and the diagnosis relies on pathological examinations combined with immunohistochemical analysis. Surgical resection can be an effective treatment modality for localized lesions;however, long-term follow-up is essential to monitor disease progression.

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

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 systematically evaluate the psychometric properties of specific self-reported outcome assessment tools for patients undergoing Endoscopic Transnasal Transsphenoidal Surgery(ETTS),with the aim of pro-viding clinical healthcare professionals with evidence to guide the selection of appropriate assessment tools.Methods A systematic search was performed across multiple databases,including the North American Skull Base Society,PubMed,Embase,CINAHL,Web of Science,Cochrane Library,CNKI,VIP database,Wanfang database,and the China Biomedical Literature Database,for studies published from the inception of each database to January 9,2025,that are related to ETTS-specific symptom assessment tools.Totally 2 independent researchers screened the literature and extracted relevant data.The consensus-based health measurement tool selection bias risk checklist and quality standards were used to evaluate the methodological quality and psychometric properties of the included studies,which helped to form the development of recommendations.Results A total of 11 articles were included,covering 8 specific self-reported outcome assessment tools for patients undergoing endonasal transsphenoidal pituitary tumor resection.Of these,the Pituitary Outcome Score and the Leiden Bother and Needs Questionnaire for patients with pituitary disease 2 tools were rated as Grade A recommendations,and 6 tools were rated as Grade B recommendations.Conclusion POS and LBNQ-Pituitary are recommended due to their relatively strong overall methodological quality and psychometric properties.However,further validation with larger sample sizes is necessary.

Objective:To establish a genomic nucleic acid mass spectrometry detection platform for allelic risk associated with Alzheimer's disease.Methods:Whole blood samples of 61 patients diagnosed as Alzheimer's disease in the Affiliated Brain Hospital of Guangzhou Medical University from December 28th, 2023 to 31st, March 2024 were collected and deoxynucleic acid (DNA) was extracted, including 22 males and 39 females, aged (67.36 ± 8.18) years old. After screening out 17 risk gene loci in Chinese population, multiplex polymerase chain reaction primers, single-base extension primers and Sanger sequencing primers were designed. Ten samples were used for primer optimization and debugging through Sanger sequencing and time-of-flight mass spectrometry to establish a detection system. The remaining samples were genotyped using a time-of-flight mass spectrometer and verified by Sanger sequencing for accuracy evaluation. Five samples were selected for gradient dilution and then subjected to time-of-flight mass spectrometry detection to evaluate the detection limit. Three clinical samples, one case of Escherichia coli and one case of Staphylococcus aureus genomic DNA samples were selected for cross-reaction research. The anti-interference ability of the detection system was evaluated against hemolysis, chylous substances and conventional anticoagulants in the samples. Two samples, one wild and one homozygous mutation sample with representative peak shapes, were selected to evaluate the anti-interference ability. Four samples containing the common genotypes of all gene loci in the system were selected and repeated 10 times to evaluate the precision.Results:The minimum intensity of single-base extension primers on mass spectrometry is greater than half of the maximum intensity. All 17 risk gene loci screened were successfully typed. The time-of-flight mass spectrometry detection results of 1,037 loci from 61 samples showed that the genotyping detection rate was 100%. The genotypes of the 20 DNA samples were completely consistent with the results of Sanger sequencing, with an accuracy rate of 100%. The mass spectrometry detection results of five samples after gradient dilution indicated that the low detection limit was 5 ng of DNA. The reaction system has a strong anti-interference ability against hemolysis of samples, chylous substances, conventional anticoagulants and DNA cross-contamination. Homologous allele interference and no cross-reaction between the bacterial genome and 17 gene loci do not affect the risk genome detection results. The results of 10 repeated mass spectrometry tests on 4 samples showed that the precision was 100%.Conclusion:The genomic detection system of Alzheimer's disease risk has been successfully established to provide an auxiliary mean for disease diagnosis and risk assessment.

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the detection of low-level mosaicisms in amniotic fluid samples, and to retrospectively analyze the rare cases of mosaicisms. METHODS: Chromosomal karyotype of the fetus was determined by G-banding analysis of cultured amniotic fluid cells. CMA was used to detect copy number variation of fetal chromosomes, and fluorescence in situ hybridization (FISH) was used to determine the proportion of fetal chromosomal mosaicisms in uncultured amniotic fluid cells. RESULTS: Among 825 prenatal samples, 4 cases of true fetal mosaicisms were detected, which yielded an incidence of 0.48%. Two cases were sex chromosomal mosaicisms, and two were autosomal mosaicisms, which involved chromosomes 8 and 9, respectively. All cases were verified by G-banding analysis of cultured amniotic fluid cells, CMA, and/or FISH. CONCLUSION CMA has a great value for detecting low-level mosaicisms in amniotic fluid samples, though the positive results need to be verified by other techniques and should be interpreted with caution. The review of rare cases can provide a basis for prenatal genetic counseling.
Humans ; Female ; Amniotic Fluid/metabolism* ; Pregnancy ; Mosaicism/embryology* ; Prenatal Diagnosis/methods* ; Adult ; In Situ Hybridization, Fluorescence ; Microarray Analysis/methods* ; Karyotyping ; Retrospective Studies ; Male