Vascular cognitive impairment (VCI), caused by cerebrovascular dysfunction, severely impacts the quality of life in the elderly population, yet effective therapeutic approaches remain limited. Mitophagy, a selective mitochondrial quality-control mechanism, has emerged as a critical focus in neurological disease research. Accumulating evidence indicates that mitophagy modulates oxidative stress, neuroinflammation, and neuronal apoptosis. Key signaling pathways associated with mitophagy—including PINK1/Parkin, BNIP3/Nix, FUNDC1, PI3K/Akt/mTOR, and AMPK—have been identified as potential therapeutic targets for VCI. This review summarizes the mechanistic roles of mitophagy in VCI pathogenesis and explores emerging therapeutic strategies targeting these pathways, aiming to provide novel insights for clinical intervention and advance the development of effective treatments for VCI.

Objective To investigate the influencing factors of disease progression and prognosis in patients with large artery atherosclerotic(LAA)cerebral infarction and analyze the value of plasma cyclin-dependent kinase 9(CDK9)level in the diagnosis and treatment of LAA cerebral infarction.Methods Patients with acute cerebral infarction admitted to the Department of Neurology of the Affili-ated Hospital of Yangzhou University between March 1,2022,and November 20,2023,were select-ed.According to the diagnostic criteria,98 patients with acute LAA(LAA group)and 33 patients with acute small artery occlusion(SAO)cerebral infarction(SAO group)were selected.Additionally,40 healthy individuals matched for age and gender from the Health Examination Center were included as control group.Based on whether the condition of LAA cerebral infarction patients progressing,they were divided into progressive cerebral infarction(PCI)group(39 patients)and the non-pro-gressive cerebral infarction(NPCI)group(59 patients).During the 3-month follow-up period,6 patients from the 98 LAA cerebral infarction patients were lost.According to the modified Rankin Scale(mRS)score at 90 days of follow-up,patients were divided into good prognosis group(mRS score≤2,59 patients)and poor prognosis group(mRS score＞2,33 patients).Fasting lipid in-dices[total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),glucose(GLU),glycated hemoglobin(HbA1c),and homocysteine(Hey)]were collected on the second day after admission.The National Institutes of Health Stroke Scale(NIHSS)was used to assess the degree of neurological impairment in cerebral infarction patients.Enzyme-linked immunosorbent assay(ELISA)was used to measure plasma CDK9 levels in different groups;factors influencing disease progression in patients with acute LAA cerebral infarction were explored;and receiver operating characteristic curves were plotted to evalu-ate the predictive value of CDK9 in patients with acute LAA cerebral infarction.Results Compared with the control group,the LAA group had lower HDL-C level and higher CDK9 level(P＜0.05).The LAA group had a higher proportion of diabetes history,larger infarction volume,higher NIHSS score at admission,and higher CDK9 level compared with the SAO group(P＜0.05).Binary Logistic regression analysis showed that diabetes history and plasma CDK9 levels were influencing factors for LAA cerebral infarction.There were statistically significant differences in the proportion of diabetes history,HbA1c,random GLU,and CDK9 levels between the NPCI and PCI groups(P＜0.05).Diabetes history and plasma CDK9 levels were influencing factors for disease progression in patients with acute LAA cerebral infarction.The area under the ROC curve for CDK9 in predicting acute LAA cerebral infarction was 0.854 5(95％CI,0.794 1 to 0.9148).When the CDK9 level was 602.1 ng/L,the Youden index was maximum(0.604),with a corresponding sensitivity of 0.849 and specificity of 0.755.The NIHSS score,infarction volume,and plasma CDK9 level were higher in the poor prognosis group compared with the good prognosis group(P＜0.01).Correlation analysis showed a positive correlation between mRS scores and CDK9 levels(r=0.485,P＜0.01).Conclusion Plasma CDK9 levels are significantly elevated,and is an influencing factor.It is positively correlated with disease progression and poor prognosis in acute cerebral infarction and has certain predictive value for the progression of LAA cerebral infarction.

Objective:To investigate the predictive value of thrombus permeability for poor outcome and symptomatic intracranial hemorrhage (sICH) after endovascular therapy (EVT) in patients with middle cerebral artery occlusion stroke.Methods:Patients with middle cerebral artery occlusion stroke underwent EVT at the Cardiocerebrovascular Disease Hospital, the Affiliated Hospital of Yan'an University from January 2018 to January 2024 were included retrospectively. Thrombus attenuation increase (TAI) was used to evaluate thrombus permeability. The poor outcome was defined as a modified Rankin Scale score >2 at 90 days after procedure. sICH was defined as an increase of ≥4 of the National Institutes of Health Stroke Scale (NIHSS) score relative to baseline or lowest within 7 days after EVT, and CT scan showed cerebral hemorrhage. Multivariate logistic regression analysis was used to determine the independent influencing factors of poor outcome and sICH. Receiver operating characteristic (ROC) curves was used to evaluate the predictive value of TAI for poor outcome and sICH. Results:A total of 77 patients with middle cerebral artery occlusion stroke received EVT treatment were enrolled, including 44 males (57.1%), aged 62.1±12.4 years. Thirty-three patients (48.1%) had poor outcome, 35 (45.5%) experienced hemorrhagic transformation, of which 12 (15.6%) were sICH. Multivariate logistic regression analysis showed that TAI (odds ratio [ OR] 0.930, 95% confidence interval [ CI] 0.883-0.980; P=0.007) and sICH ( OR 0.868, 95% CI 0.784-0.961; P=0.006) were the independent influencing factors of poor outcome. ROC curve analysis showed that the area under the curve of TAI for predicting poor outcome at 90 days was 0.836 (95% CI 0.742-0.930). The cut-off value was 10.135 HU. The sensitivity and specificity were 73.0% and 92.5%, respectively. The area under the curve of TAI for predicting sICH was 0.750 (95% CI 0.637-0.902). The cut-off value was 18.200 HU. The sensitivity and specificity were 94.1% and 64.5%, respectively. Conclusions:TAI has certain predictive value for poor outcome and sICH after EVT in patients with middle cerebral artery occlusion stroke. Patients with higher thrombus permeability are less likely to develop sICH after EVT and have a higher likelihood of good outcome.

Objective:To explore the genetic etiology of a child with delayed growth and development and carry out a literature review.Methods:A child suspected for Al Kaissi syndrome at the First Affiliated Hospital of Zhengzhou University on March 6, 2021 was selected as the study subject. Following extraction of genomic DNA, the child was subjected to copy number variation sequencing (CNV-seq) and whole exome sequencing (WES), and candidate variants were verified by PCR-agarose gel electrophoresis and quantitative real-time PCR (qPCR). Prenatal diagnosis was conducted on chorionic villi sample upon subsequent pregnancy.Results:The child, a 6-year-and-4-month-old boy, has dysmorphic features including low-set protruding ears and triangular face, delayed language and intellectual development, and ventricular septal defect. CNV-seq result has found no obvious abnormality, whilst WES revealed homozygous deletion of exons 1 and 2 of the CDK10 gene, which was confirmed by PCR -agarose gel electrophoresis and qPCR. Both of his parents were heterozygous carriers. Prenatal diagnosis using chorionic villi samples suggested that the fetus also carried the heterozygous deletion.Conclusion:The clinical features of Al Kaissi syndrome in this child can probably be attributed to the homozygous deletion of exons 1 and 2 of the CDK10 gene.

Hemophagocytic lymphohistiocytosis (HLH) is a rare immune-mediated disorder characterized by hyperactivation of antigen-presenting cells and T cells, massive secretion of inflammatory cytokines, and impaired function of natural killer cells and CD8 + T cells.Ruxolitinib is a Januse kinase(JAK)inhibitor that reduces cytokine release and retards the inflammatory response by competitive binding to the JAK catalytic site, to achieve the goal of curing HLH.In recent years, ruxolitinib has been gradually applied in the treatment of HLH, and its effectiveness has also been verified.However, studies have also found that there are efficacy differences in the treatment of HLH caused by different etiologies.This article reviews the mechanism of ruxolitinib in the treatment of HLH and the differences in the efficacy of ruxolitinib in the treatment of HLH of different etiologies.

Hazardous environmental factors as well as occupational factors can lead to elevated incidence of diseases including tumors, and specific molecular biomarkers are needed to guide the diagnosis and treatment of diseases. In recent years, ubiquitin-specific protease 14 (USP14) has gradually attracted the attention of researchers. USP14 is widely expressed in various organs of human body and regulates the stability and degradation of important proteins in various signaling pathways. Studies have shown that its abnormal expression is highly correlated with tumors, neurodegenerative diseases, autophagy, immune response, and viral infections, and is involved in the regulation of various classic signaling pathways. It has been shown to play a key role in the development of various human diseases and can be used as a diagnostic and prognostic molecular biomarker and therapeutic target in the development of tumors. This paper reviewed the current status of research on the structure and regulation of USP14 and its function in physiological and pathological processes, with the aim of providing a reference for research on diseases or injuries caused by environmental and occupational factors.

Autoimmune diseases of the nervous system are a group of diseases caused by the body′s immune system attacking its own nervous system, resulting in structural damage and functional impairment of the corresponding tissues. Interventional clearance of pathogenic auto-antibodies has been shown to be effective in reducing immune damage, inhibiting disease progression and improving prognosis through extensive basic research and long-term clinical practice. The neonatal Fc receptor (FcRn)-mediated circulating protection mechanism of IgG contributes to the long half-life and high plasma levels of IgG. FcRn inhibitors are able to target and block the binding of FcRn to IgG, accelerating IgG clearance and reducing IgG levels. Therefore, the use of FcRn inhibitors in the treatment of autoimmune diseases of the nervous system could theoretically help to accelerate the clearance of pathogenic IgG, achieve good clinical efficacy and have promising applications. Research in this area has made considerable progress in recent years and this article will review this.

Objective Using event-related potentials(ERPs),to study the effect and mechanism of negative emotion accumulation hepatic insufficiency on working memory in normal people.Methods Fifty subjects in each of the emotionally stable group and emotionally unstable group were given two load tasks(0-back and 1-back)in the N-back paradigm,the reaction time and correct rate were recorded,and the ERPs components N200 and P300 were detected.The latency and amplitude of P300 were analyzed statistically.Results ①Compared with the emotionally stable group,the emotionally unstable group had a longer reaction time(P<0.05).②Compared with the emotionally stable group,the subjects in the emotionally unstable group had prolonged N200 latency,decreased P300 amplitude significantly(P<0.05),and P300 latency had a tendency to extend(P<0.1).Conclusion Long-term accumulation of negative emotions and liver failure in normal people have the performance of decreased working memory,which may be related to the reduction of attention resource allocation and the impairment of cognitive processing function.

OBJECTIVE: To explore the clinical and genetic features of a child with autosomal dominant mental retardation type 40 (MRD40) due to variant of the CHAMP1 gene. METHODS: Clinical characteristics of the child were analyzed. Genetic testing was carried out by low-depth high-throughput and whole genome copy number variant sequencing (CNV-seq) and whole exome sequencing (WES). A literature review was also carried out for the clinical phenotype and genetic characteristics of patients with MRD40 due to CHAMP1 gene variants. RESULTS: The child, a 11-month-old girl, has presented with intellectual and motor developmental delay. CNV-seq revealed no definite pathogenic variants. WES has detected the presence of a heterozygous c.1908C>G (p.Y636*) variant in the CHAMP1 gene, which was carried by neither parent and predicted to be pathogenic. Literature review has identified 33 additional children from 12 previous reports. All children had presented with developmental delay and mental retardation, and most had dystonia (94.1%), delayed speech and/or walking (85.2%, 82.4%) and ocular abnormalities (79.4%). In total 26 variants of the CHAMP1 gene were detected, with all nonsense variants being of loss-of-function type, located in exon 3, and de novo in origin. CONCLUSION The heterozygous c.1908C>G (p.Y636*) variant of the CHAMP1 gene probably underlay the WRD40 in this child. Genetic testing should be considered for children featuring global developmental delay, mental retardation, hypertonia and facial dysmorphism.
Humans ; Intellectual Disability/genetics* ; Genetic Testing ; Phenotype ; Exome Sequencing ; Heterozygote ; Mutation ; Chromosomal Proteins, Non-Histone/genetics* ; Phosphoproteins/genetics*

Hedgehog （Hh） signaling pathway plays an important regulatory role in the process of cell proliferation， differentiation and tissue formation. Proper intensity and action time of Hh signal are crucial for the normal development of various tissues of the body， and its abnormal activation will lead to the occurrence and development of most malignant tumors， including breast cancer， liver cancer， pancreatic cancer， and lung cancer， which makes Hh signaling pathway an ideal target for anti-tumor drug research and development. At present， the main targets of Hh signaling pathway inhibitors include Hh ligand， receptor Smoothened （Smo） and transcription factor Gli. Among them， the compounds that depend on the Hh ligand pathway still remain at the stage of laboratory research because they cannot act on the non-classical Hh signaling pathway. The special structure of Smo protein enables it to combine with drugs efficiently and selectively， which is a powerful and effective drug target. Therefore， Smo selective inhibitors have been an active field of related research， and many Smo inhibitors have entered the clinical use or trial stage. Gli can regulate multiple carcinogenic genes， promote abnormal cell proliferation and lead to tumor， and can also cause feedback inhibition to Hh signaling pathway. Therefore， the development of drugs that can inhibit the activity of Gli has broad prospects. In the future， a combination of multiple pathway inhibitors can be designed to avoid drug resistance and other side effects.