In different stages of schizophrenia (SZ), alterations in gray matter volume (GMV) of patients are normally regulated by various pathological mechanisms. Instead of analyzing stage-specific changes, this study employed a multivariate structural covariance model and sliding-window approach to investigate the illness duration-related developmental trajectory of GMV in SZ. The trajectory is defined as a sequence of brain regions activated by illness duration, represented as a sparsely directed matrix. By applying this approach to structural magnetic resonance imaging data from 145 patients with SZ, we observed a continuous developmental trajectory of GMV from cortical to subcortical regions, with an average change occurring every 0.208 years, covering a time window of 20.176 years. The starting points were widely distributed across all networks, except for the ventral attention network. These findings provide insights into the neuropathological mechanism of SZ with a neuroprogressive model and facilitate the development of process for aided diagnosis and intervention with the starting points.
Humans ; Schizophrenia/pathology* ; Gray Matter/pathology* ; Magnetic Resonance Imaging ; Disease Progression ; Male ; Female ; Brain/pathology* ; Cerebral Cortex/pathology* ; Adult

Objective:To investigate the effects and molecular mechanisms of Wilms tumor 1-associated proteins(WTAP)on the cell biological properties of esophageal squamous cell carcinoma(ESCC)cells.Methods:31 pairs of ESCC tissues and their paired paracancerous tissues that were surgically resected at the Second Clinical Medical College of Chuanbei Medical College between September 2019 and April 2021 were collected.The esophageal cancer cells KYSE30,KYSE410,KYSE150,KYSE510,TE-1,and normal human esophageal epithelial cells HET-1A were routinely cultured.Transfection reagents were used to transfect si-NC,si-WTAP#1 and si-WTAP#2 nucleic acids into KYSE150 and KYSE510 cells.The cells were divided into si-NC,si-WTAP#1 and si-WTAP#2 groups.The expressions of WTAP and MAP3K9 mRNA were detected in the cells of each group by qPCR assay.CCK-8 assay,clone formation assay,and scratch healing assay,Transwell assay were employed to detect the effects of knockdown of WTAP expression on ESCC cell proliferation,migration,invasion and apoptosis.WB assay was used to detect the expressions of WTAP,MAP3K9,EMT and MAPK pathway-related proteins in ESCC cells of each group knocked down of WTAP;immunohistochemistry to detect the expression of WTAP proteins in ESCC tissues,immunoprecipitation of methylated RNA(MeRIP)-qPCR assay to detect the level of MAP3K9 m6A in ESCC cells,actinomycin D assay to detect the stability of mRNA of MAP3K9,and database data to analyze the expression,target genes,functional enrichment,and interacting RNA of WTAP.Results:WTAP was highly expressed in ESCC tissues and cells(P<0.05 or P<0.01 or P<0.001)and correlated with the degree of differentiation(P<0.01);the expression of WTAP mRNA and its protein were successfully knocked down in KYSE150 and KYSE510 cells(P<0.01 or P<0.001);the knockdown of WTAP significantly inhibited the proliferation,migration and invasion of KYSE150 and KYSE510 cells(P<0.05 or P<0.01 or P<0.001),and promoted the apoptosis of KYSE150 and KYSE510 cells(P<0.05 or P<0.01).Knockdown of WTAP resulted in a significant decrease in the m6A level of MAP3K9(P<0.05),and its mRNA expression level and mRNA stability were both significantly reduced(P<0.05).Database data analysis showed that WTAP target genes clustered in the MAPK signaling pathway;the expression levels of MAP3K9,p-ERK,N-cadherin,and MMP9 were significantly reduced(P<0.05 or P<0.01),and the expression level of E-cadherin was significantly elevated(P<0.05 or P<0.01)in the KYSE150 and KYSE510 cells after knockdown of WTAP.Conclusions:WTAP is highly expressed in ESCC tissues and cells and correlates with their differentiation.It promotes the stability of MAP3K9 mRNA through m6A modification,activates the MAPK pathway and thus promotes the malignant biological behaviors of ESCC cells.

Objective To compare the safety and adverse effects of esketamine alone or fentanyl combined with propofol for interventional occlusion of congenital heart disease in children,so as to provide a more suitable sedation and analgesia plan for these patients.Methods A prospective randomized controlled study was adopted.A total of 104 cases of congenital heart disease,including 53 cases of atrial septal defect(ASD),31 cases of ventricular septal defect(VSD),and 20 cases of patent ductus arteriosus(PDA),who underwent interventional occlusion under general anesthesia while preserving spontaneous breathing from January to March 2025,were taken as the research subjects.The children were divided into two groups by random number table method:esketamine group(group ES)and fentanyl+propofol group(group AP),with 52 cases in each group.The children in the group ES and the group AP were anesthetized by esketamine 0.5 mg/kg and fentanyl 2 ug/kg+propofol 2.5 mg/kg,respectively,and sevoflurane inhalation anesthesia was maintained during the operation.The mean arterial pressure(MAP),heart rate(HR),respiratory rate(RR)and pulse oxygen saturation(SpO2)were recorded at the time of entry(T0),1 min after induction of general anesthesia(T1),femoral artery puncture(T2),occluder insertion(T3),recovery(T4),and 10 min after recovery(T5).The operation time,dosage of sevoflurane,anesthesia induction time and recovery time of the two groups were recorded.The occurrence of adverse events during general anesthesia was recorded,including hypoxemia after general anesthesia induction,respiratory depression and intraoperative body movement,restlessness during the recovery period,and increased secretion during the recovery period.Results There were significant differences in MAP,HR,SpO2 and RR in time points within each group,between two groups,and across the time×group interaction(P<0.05).There was no significant difference in operation time,dosage of sevoflurane,anesthesia induction time,and recovery time between the two groups(P>0.05).The incidence of hypoxemia in the group ES was significantly lower than that in the group AP[1.9%(1/52)vs.28.9%(15/52),χ2=14.477,P=0.000],the incidence of respiratory depression in the group ES was significantly lower than that in the group AP[0.0%(0/52)vs.11.5%(6/52),P=0.027],and the incidence of intraoperative body movement in the group ES was significantly lower than that in the group AP[0.0%(0/52)vs.11.5%(6/52),P=0.027].Conclusions During the three interventional occlusion procedures for congenital heart disease in children,compared with fentanyl combined with propofol injection,esketamine can better maintain the stability of respiratory circulation,and has a lower incidence of adverse events such as intraoperative hypoxemia,respiratory depression and intraoperative body movement.Compared with traditional anesthetic drugs,eketamine can be used as a better choice for sedation and analgesia during interventional occlusion for the three types of congenital heart diseases in children.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Objective:To construct a prognostic risk model based on lactate metabolism-related genes screened using bioinformatics methods in renal cell carcinoma patients，and investigate the clinical prognosis and immune characteristics of renal cell carcinoma.Methods:Gene expression data and clinical information of patients with renal cell carcinoma were downloaded from the Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma（TCGA-KIRC）dataset. Lactate metabolism-related gene sets were obtained from the Gene Set Enrichment Analysis（GSEA）database. The R package DEseq2 was employed to identify differentially expressed genes associated with lactate metabolism within the TCGA-KIRC dataset. GO and KEGG enrichment analyses were performed using the clusterProfiler package. Prognosis-related genes were screened via univariate Cox regression analysis and the intersection with lactate metabolism-related differentially expressed genes was obtained. A risk model was constructed using LASSO regression followed by multivariate Cox regression analysis to calculate risk scores. This risk model was subsequently validated using the GSE29609 dataset. Patients were stratified into high-risk and low-risk groups based on the median risk score. The expression profiles of key immune molecule genes and immune checkpoint genes were compared between the two groups. Survival analysis curves for immune checkpoint genes were generated using the survival and survminer R packages. Differences in tumor mutation burden（TMB）between the high-risk and low-risk groups were assessed，and corresponding TMB survival analysis curves were plotted. Finally，the tumor immune dysfunction and exclusion（TIDE）algorithm was used to evaluate disparities in immunotherapy response potential between the two risk groups.Results:An optimal prognostic risk model incorporating seven lactate metabolism- and prognosis-related genes（ LDHD，PER2，ACADM，FLI1，LIPA，TCIRG1，SLC25A4）was constructed and successfully validated in the GSE29609 dataset. Univariate Cox regression analysis revealed that a high-risk score was significantly associated with poor prognosis（ HR=2.915，95% CI：2.451-3.470， P<0.001）. Multivariate Cox regression analysis confirmed that this risk model could serve as an independent prognostic factor for patients with renal cell carcinoma（ HR=2.231，95% CI：1.829-2.722， P<0.001）. Patients in the high-risk group exhibited significantly worse outcomes compared to the low-risk group，regardless of whether they had early-stage or advanced-stage renal cell carcinoma（both P<0.001）. Analyses related to the immune microenvironment indicated an upregulated immunosuppressive phenotype in the high-risk group. Furthermore，the TMB was significantly higher in the high-risk group than in the low-risk group（ P=0.032），and patients within the high-risk group exhibiting higher TMB levels demonstrated even poorer survival（ P<0.001）. Finally，the TIDE score was significantly elevated in the high-risk group in comparison to the low-risk group（ P<0.001）. Conclusions:The risk model based on lactate metabolism-related genes constructed in this study can guide the prognosis of renal cell carcinoma. Patients in the high-risk group are more prone to immune escape and formation of an inhibitory immune microenvironment，leading to worse prognoses. This risk model may serve as a biomarker for predicting immunotherapy response.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

The incidence of type 2 diabetes mellitus (T2DM) has been continuously rising, severely impacting health and increasing the medical burden. With the development of medical big data and artificial intelligence, research into constructing T2DM and its complications prediction models using machine learning methods based on multidimensional data such as genetic information, health records and laboratory testing data have increased, providing new ideas and means for the prevention and control of T2DM. This article reviewed the research progress in prediction models related to the risk of T2DM to understand the classification, modeling methods and applications by retrieving literature on T2DM and its complications prediction models from domestic and international databases including CNKI, Web of Science, and PubMed from 2003 to 2024, so as to provide the reference for early screening and intervention of T2DM.

Objective To establish a rat model of postoperative delirium(POD)induced by cardiopulmonary bypass with human gut microbiota using fecal microbiota transplantation(FMT)technology,and evaluate the model based on bioinformatics,cytokine analysis,and behavioral testing methods.Methods SPF-grade adult male SD rats weighing 400 to 450 g were selected.After under-going a week of Morris water maze training,rats with consistent performance were used to construct pseudo-germ-free rat models.Subsequently,20 successfully modeled rats were randomly divided into two groups:(CON group receiving fecal microbiota filtrate from healthy individuals)and(POD group receiving fecal microbiota filtrate from POD patients).Behavioral tests were conducted two weeks af-ter modeling,and rat feces were collected for metagenomic sequencing.Rats were euthanized by cer-vical dislocation,and blood and brain tissue samples were collected for cytokine and histopathological examinations.Results Compared with the CON group,the POD group exhibited significantly increased relative abundances of Akkermansiaceae,Prevotellaceae,and Akkermansia muciniphila,while the relative abundances of Lactobacillaceae and Mediterraneibacter massiliensis decreased significantly(P＜0.05).Serum levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α were signif-icantly higher in the POD group than those in the CON group(P＜0.05).Hematoxylin-eosin(HE)staining in the POD group revealed neurons with pyknotic and hyperchromatic nuclei.After modeling,the average latency in the Morris water maze was significantly longer in the POD group than that in the CON group(P＜0.05).Conclusion This study utilizes fecal microbiota trans-plantation technology to establish a rat model of POD induced by cardiopulmonary bypass with hu-man gut microbiota.The changes in gut microbiota structure abundance,levels of POD-related in-flammatory factors,and Morris water maze test results in this model are similar to the clinical mani-festations observed in patients with POD induced by cardiopulmonary bypass.

Objective To analyze the mutation status of Kirsten rat sarcoma viral oncogene homolog(KRAS),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),v-raf murine sarcoma viral oncogene homolog B1(BRAF)genes,and the expression of mismatch repair(MMR)and human epidermal growth factor receptor 2(HER-2)proteins in tumor tissues of patients with colorectal cancer(CRC)harboring neuroblastoma rat sarcoma viral oncogene homolog(NRAS)gene mutations,and explore their relationships with the clinicopathological characteristics of CRC patients.Methods The clinicopathological data of 546 patients with NRAS mutation CRC were retrospectively analyzed.The mutation status of NRAS,KRAS,PIK3CA,and BRAF genes was detected by AmoyDx amplification refractory mutation system(ARMS)-polymerase chain reaction(PCR)kit(fluorescent PCR method),the expression levels of MMR and HER-2 proteins were detected by immunohistochemical staining EnVision method,and the relationship between them and the clinicopathological characteristics of patients were analyzed.Results The mutation rate of single-point mutations in the NRAS gene was 98.35%(537/546),double-point mutations in the NRAS gene were 1.65%(9/546),and double mutations in the NRAS and KRAS genes were 1.47%(8/546).No patients were found to harbor mutations in the PIK3CA or BRAF genes.The types of NRAS mutations included Q61R(or Q61K,Q61L,Q61H)mutations(266/546,48.72%),G12D(or G12S)mutations(154/546,28.21%),G13R(or G12C,G12V,G12A,G13V)mutations(134/546,24.54%),and A146T mutation(1/546,0.18%).G13R(or G12C,G12V,G12A,G13V)mutations in the NRAS gene were more likely to occur in the rectum cancer patients(P=0.035);although the tumors had a larger diameter(P=0.029),the patients had a longer progression-free survival after surgery(P=0.028).Among patients with NRAS gene mutations,HER-2 positive expression was associated with perineural invasion(P=0.003),and the patients with deficient MMR were younger on average(P=0.041)and were associated with double-point mutations in the NRAS gene(P=0.018).Conclusion CRC harboring NRAS mutations may have unique clinicopathological characteristics and molecular phenotypes,providing possibilities for individualized treatment and prognosis evaluation of CRC.