While cranial radiotherapy effectively kills tumor cells and significantly prolongs patient survival, it often leads to progressive cognitive decline. To date, the specific mechanisms underlying radiation-induced cognitive decline have not been fully elucidated, which greatly limits the development of related therapeutic strategies. Therefore, this article provides a comprehensive analysis of post-radiation changes in neurogenesis, neuronal synaptic plasticity, myelin injury plasticity, and parenchymal cells such as microglia in the brain, systematically elucidates the potential mechanisms of radiation-induced cognitive decline, and summarizes feasible therapeutic approaches. These findings provide a solid foundation for developing novel strategies to mitigate radiation-induced cognitive decline.

ObjectiveTo investigate the potential targets of 2，5-dihydroxybenzoic acid （2，5-DHBA） in the treatment of metabolic dysfunction-associated fatty liver disease （MAFLD） and the molecular mechanism by which it regulates the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway. MethodsA network pharmacology analysis was performed at first， and related databases were used to obtain the common action targets of 2，5-DHBA and MAFLD， followed by molecular docking and pathway enrichment analysis to predict the potential biological processes and signaling pathways regulated by these targets. Then mouse normal hepatocytes AML-12 were used for cell experiments， and CCK-8 assay was used to determine the three optimal intervention concentrations of 2，5-DHBA. AML-12 cells were divided into control group， model group （cells cultured in a medium containing 2 mmol/L free fatty acid ［FFA］ to establish a cell model of MAFLD）， and three 2，5-DHBA intervention groups （cells cultured with FFA and 2，5-DHBA at the three different concentrations of 1.25， 5， and 20 μmol/L， respectively）. Oil red O staining was used to observe intracellular lipid accumulation； the fluorescent probe DCFH-DA was used to measure the level of intracellular reactive oxygen species （ROS）； biochemical assays were used to measure the content of triglyceride （TG） and total cholesterol （TC）； quantitative real-time PCR and Western Blot were used to measure the expression levels of related genes and proteins. A one-way analysis of variance was used for comparison between multiple groups， and the Tukey’s test was used for further comparison between two groups. ResultsA total of 32 common targets were obtained for 2，5-DHBA and MAFLD. Within a concentration range of 1.25 — 20 μmol/L， 2，5-DHBA treatment， starting from the concentration of 2.5 μmol/L， increased the viability of AML-12 cells in a dose-dependent manner. The minimum effective concentration of 1.25 μmol/L， the intermediate gradient concentration of 5 μmol/L， and the maximum safe concentration within the effective range of 20 μmol/L were selected for low-， middle-， and high-dose intervention， respectively. Compared with the model group， 2，5-DHBA intervention at concentrations of 1.25， 5， and 20 μmol/L could significantly reduce lipid droplet accumulation in cells （all P<0.05）， and there were significant differences in TG and TC between the model group and the three intervention groups （all P<0.05）. Compared with the control group， the model group had a significant increase in ROS fluorescence intensity （P<0.05）， and compared with the model group， there was a dose-dependent reduction in intracellular ROS level after treatment with 5 μmol/L or 20 μmol/L 2，5-DHBA （P<0.05）. Compared with the model group， 2，5-DHBA treatment at concentrations of 5 and 20 μmol/L significantly downregulated the mRNA expression levels of the lipogenic genes SREBf1 and FASN and upregulated the mRNA expression levels of the key antioxidant gene Nrf2 and its downstream target gene HO-1 （all P<0.05）. Compared with the control group， the expression of p-PI3K/PI3K and p-Akt/Akt in the model group was significantly increased （all P<0.05）. Compared with the model group， the protein expression levels of p-PI3K/PI3K and p-Akt/Akt were significantly decreased after 5 μmol/L 2，5-DHBA treatment （P<0.05）. Compared with the control group， the expression levels of Nrf2 and HO-1 protein in the model group were significantly decreased （all P<0.05）. The protein levels of Nrf2 and HO-1 were significantly increased after treatment with 1.25 μmol/L 2，5-DHBA （P<0.05）. ConclusionNetwork pharmacology and cellular experiments confirm that 2，5-DHBA can alleviate lipid deposition and oxidative stress by regulating the PI3K/Akt signaling pathway， thereby exerting a therapeutic effect on MAFLD.

Objective To systematically evaluate the similarities between six-gene-modified pig red blood cells and human red blood cells in multiple dimensions, including cell morphology, hematological parameters, microbial safety and serological compatibility, and to verify the feasibility of using six-gene-modified pig red blood cells as an alternative for blood transfusion in cases of traumatic hemorrhage. Methods Blood samples from O-type human donor, six-gene-modified O-type pig and wild-type O-type pig were collected. The pig gene-modified phenotype was identified by flow cytometry. The morphology was observed using field emission scanning electron microscopy and the diameter was measured. Hematological tests, including blood routine, osmotic fragility test, adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) content and partial pressure of oxygen at 50% hemoglobin saturation (P50), were conducted to assess the deformability of red blood cells. Real-time fluorescent quantitative polymerase chain reaction was used to screen for zoonotic viruses, and cross-matching was performed using column gel method, condensation amine method and saline tube method. Results The six-gene-modified pig red blood cells successfully knocked out the α-Gal, Neu5Gc and Sda antigens and expressed hCD55. Wild-type pig red blood cells expressed these three antigens but did not express human complement regulatory proteins. All three types of red blood cells presented a biconcave discoid morphology. The diameter of O-type human red blood cells was larger than that of the six-gene-modified porcine red blood cells and wild-type pig red blood cells (all P < 0.05). The average red blood cell volume and average red blood cell hemoglobin of O-type humans were higher than those of the six-gene-modified pig red blood cells, and the distribution width-variable coefficient of O-type human red blood cells was lower than that of the six-gene-modified pig red blood cells (all P < 0.05). There were no statistically significant differences in the permeability fragility, ATP content, 2,3-DPG content, P50 and red blood cell deformability indicators of the three types of red blood cells (all P > 0.05). The screening for zoonotic viruses in human and animal cells of the six-gene-modified pigs and wild-type pigs was negative. The cross-matching results showed that in the column gel method and condensation amine method, the primary and secondary sides of the six-gene-modified pig red blood cells did not agglutinate with human red blood cells, while the wild-type pig red blood cells agglutinated with human red blood cells in all cross-matching methods. Conclusions The six-gene-modified pig red blood cells are highly similar to human red blood cells in terms of morphology, key hematological parameters, energy metabolism, oxygen-carrying capacity, mechanical properties, microbial safety and serological compatibility, providing an experimental basis for the clinical transformation of xenotransfusion.

Autism spectrum disorder(ASD) is a neurodevelopmental disorder, and social impairment was one of the core symptoms of ASD, which can seriously affects the social life of patients.The pathogenesis of social impairment in ASD is unclear and it may involves many brain abnormalities.The related theories and hypotheses are numerous and there is no unified conclusion. Studies have shown that the cerebellum has extensive connections with brain networks and is involved in the regulation of social cognition, but its role in ASD has not been fully emphasized.The structural and functional abnormalities of the cerebellar-cortex (CC) loop in ASD patients can lead to language communication disorders, empathy disorders, difficulties in interpreting social cues, abnormal social reward processing and emotional regulation disorders, which are closely related to ASD social impairment. Noninvasive brain stimulation of the superficial cerebellum can improve the abnormal CC circuit in ASD patients, and the cerebellum can be considered as a target for the treatment of social disorders in ASD in the future.Based on the clinical and basic researches on social impairment in ASD in recent years, this article reviews the relevant manifestations of disorders which cerebellar and CC circuit involved, aiming to promote the development of related research in the future.

As the incidence of autism rises annually,its unknown pathogenesis makes it challenging to treat the varied repetitive and stereotyped behaviors that characterize its core symptoms.The striatum is an important brain region for the control of locomotor behaviors,featuring a unique mosaic structure,complex neural origin,and finely regulated developmental process that is highly susceptible to genetic and environmental influences.Both clinical and basic studies have indicated that abnormal development of the striatal nuclei may contribute to the pathogenesis of these repetitive stereotyped behaviors in autism.Clinical imaging data have primarily identified gross anatomical variations in the stratum(e.g.,its general outline),but lack the resolution necessary to detect the cellular and subcellular alterations within the region.By introducing the abnormalities in the spatiotemporal development of the striatum and their links to the characteristic behaviors of autism,this review aims to advance our understanding of the role of the striatum in autism pathogenesis and to inform future animal studies and clinical research.

Objective To explore the protective effects of genetically modified porcine erythrocyte suspension as a subnormothermic normoxic mechanical perfusate on hypoxic-ischemic brain injury in cynomolgus monkeys caused by traumatic hemorrhage.Methods Cynomolgus monkeys were randomly divided into positive and negative control groups(a total of 3 monkeys,with 3 left cerebral hemispheres as the positive control group and 3 right cerebral hemispheres as the negative control group)and the subnormothermic perfusion group(n=3).The positive control group was directly sampled 1 hour after circulatory arrest,while the negative control group was placed at subnormothermic conditions for 6 hours after circulatory arrest.The subnormothermic perfusion group underwent 6 hours of subnormothermic normoxic mechanical perfusion of the bilateral common carotid arteries of the cynomolgus monkey hypoxic-ischemic brain injury model using genetically modified porcine erythrocyte suspension 1 hour after circulatory arrest.Before perfusion,cross-matching experiments were conducted between the six genetically modified pig and the cynomolgus monkeys.After the start of perfusion,the levels of routine blood indicators in the perfusate were detected at 0,1,2,3,4,5 and 6 hours.Blood oxygen saturation was recorded,and the levels of Na+,K+,Ca2+,glucose and blood pH in the perfusate were measured,as well as the levels of IgG and IgM in the perfusate.After 6 hours of perfusion,the water content of the brain tissue was measured.Nissl staining was performed on the frontal cortex and hippocampal regions,and immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP),ionized calcium-binding adapter molecule 1(Iba1)and neuronal nuclear antigen(NEUN).Results The cross-matching results between the six genetically modified pig and the cynomolgus monkeys were negative.The number of red blood cells in the perfusate decreased significantly at 3 hours of perfusion,and the hemoglobin level showed a downward trend at 1,3,5 and 6 hours.The number of white blood cells and platelets decreased at all time points.The blood oxygen saturation in the subnormothermic perfusion group remained stable at 95%-98%,and the levels of blood oxygen saturation,Na+,Ca2+,glucose and pH were stable,while the K+level first increased and then decreased.There was no significant difference in the levels of IgG and IgM before and after perfusion.The water content of brain tissue at the end of perfusion in the subnormothermic perfusion group was significantly higher than that in the positive control group(P<0.001).Nissl staining results showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex of the subnormothermic perfusion group maintained better morphological integrity,with no significant increase in enlarged and deformed cells.In the hippocampal CA1 region,there was a slight increase in enlarged and deformed cells,and a few cells with undamaged structures showed reduced cell size.In the hippocampal dentate gyrus,fewer granule neurons had compromised structural integrity,with increased cell edema.NEUN immunofluorescence staining showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex and hippocampal CA1 region of the subnormothermic perfusion group had better morphological states,with clear axons.The granule cells in the hippocampal dentate gyrus were well preserved,but the nuclei were less well protected.GFAP immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had sparser protrusions that were more tightly associated with neurons.Iba1 immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had thicker and fewer protrusions.Conclusions Compared with the positive control group,subnormothermic normoxic mechanical perfusion with genetically modified porcine erythrocyte perfusate increases brain tissue edema in cynomolgus monkeys,but better preserves the morphological integrity of neurons and glial cells.The protective effects may be related to the continuous oxygen and energy supply,maintenance of ion homeostasis and perfusate pH,reduced rejection,and low metabolic state of the whole brain.

Autism spectrum disorder(ASD) is a neurodevelopmental disorder, and social impairment was one of the core symptoms of ASD, which can seriously affects the social life of patients.The pathogenesis of social impairment in ASD is unclear and it may involves many brain abnormalities.The related theories and hypotheses are numerous and there is no unified conclusion. Studies have shown that the cerebellum has extensive connections with brain networks and is involved in the regulation of social cognition, but its role in ASD has not been fully emphasized.The structural and functional abnormalities of the cerebellar-cortex (CC) loop in ASD patients can lead to language communication disorders, empathy disorders, difficulties in interpreting social cues, abnormal social reward processing and emotional regulation disorders, which are closely related to ASD social impairment. Noninvasive brain stimulation of the superficial cerebellum can improve the abnormal CC circuit in ASD patients, and the cerebellum can be considered as a target for the treatment of social disorders in ASD in the future.Based on the clinical and basic researches on social impairment in ASD in recent years, this article reviews the relevant manifestations of disorders which cerebellar and CC circuit involved, aiming to promote the development of related research in the future.

Purpose To investigate the clinicopathological features and differential diagnosis of anaplastic large-cell lymphoma(ALCL)with the small cell variant.Methods The clinical data of 15 cases of small cell variant of ALCL were retrospectively analyzed.Hematoxylin-eosin staining,immunohistochemistry,EBER in situ hybridization,TCR and IgG rearrangement were performed.The clinicopathological features,prognosis and differential diagnosis were summarized with review of the literature.Results Among the 15 cases of small cell ALCL,5 were females and 10 were males,with a male-to-female ratio of 2:1.Among the 15 cases of small cell ALCL,14 were systemic ALCL[(12 cases of ALK+),and the age range was 5-63 years old(median age 20 years);There were 2 cases of ALK(-),aged more than 60 years],and 1 case of ALCL of primary cutaneous ALK(-).Microscopic features were dominated by small to medium-sized tumor cells,with irregular nuclear membranes,inconspicuous nucleoli,and a lack of or few iconic large cells.Immunohistochemically:3 cases were ALK-negative and 12 cases were ALK-positive.Tumor cells were CD30 positive in 14/15 cases,CD3 positive in 7/15 cases,CD2 positive in 2/6 cases,CD4 positive in 5/11 cases,CD5 positive in 2/8 cases,CD7 positive in 4/6 cases,CD8 positive in 1/8 cases,TIA-1 positive in 7/7 cases,Granzyme B positive in 4/6 cases and EMA positive in 6/7 cases.CD20 was negative in all cases.Immuno-globulin IgG and TCR gene rearrangement were negative in case 4 and case 11.Case 13 was positive for TCR rear-rangement and negative for immunoglobulin IgG.Twelve of the 15 patients were followed up for 0.7-165 months(me-dian,7 months),3 patients were lost to follow-up and 7 patients died.Conclusion Small cell variant ALCL is easily misdiagnosed as an inflammatory or infectious disease.A group of antibodies,including CD30 and ALK,should be routinely used in routine work,especially in young patients with systemic symptoms and leukemia manifestations or in small biopsies,to reduce misdiagnosis and missed diagnosis.

Objective:To investigate the related factors of hyperuricemia(HUA)in adolescents with bipolar disorder.Methods:Fifty-nine adolescent patients with bipolar disorder and 60 normal controls were select-ed.General demographic and clinical data were collected.Serum uric acid(UA),triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),fasting blood glucose(FPG),fructosamine(FA)and other physiological indices were detected.The Hamilton Depression Scale 17(HAMD-17)and Bech-Rafaelsen Mania Scale(BRMS)were used to evaluate the emotional symptoms of the patients.Results:The detection rate of HUA was higher in the adolescent patients with bipolar disorder than in the normal control group(30.5％vs.18.3％,P＜0.05),and was higher in manic episode than in depressive episode(48.2％vs.20.8％,P＜0.05).Unconditioned logistic regression analysis showed that high level of TG and high BMI were risk factors for hyperuricemia in adolescents with bipolar disorder(OR=2.51,1.34).Conclusion:This study shows that adolescents with bipolar disorder may have a higher risk of HUA than normal controls,and its oc-currence is associated with high TG level and BMI.

Objective:To investigate the clinical, cytopathological characteristics, and differential diagnosis of metastatic clear cell renal cell carcinomas (CCRCC).Methods:Nine cases of metastatic CCRCC cytologically diagnosed in the Department of Pathology, the First Affiliated Hospital of Air Force Medical University from July 2021 to December 2024 were collected. The HE staining, May-Grunewald-Giemsa staining, liquid-based slides, cell block preparation, and immunocytochemistry of EnVision two-step staining were performed. The clinical and cytopathological features, treatments and follow-up data were analyzed in combination with literature review.Results:Among the 9 cases of metastatic CCRCC, there were 7 males and 2 females. The age range was 43-78 years, and the average age was 63.6 (57.5, 72.5) years. The metastatic sites were lymph node in 3 cases (2 cases of mediastinal lymph nodes and 1 case of left cervical lymph node), bone in 3 cases (pubis, thoracic vertebrae and femur, respectively), thyroid in 2 cases, and adrenal gland, lung and pancreas in 1 case, respectively. Two of the 9 cases had two metastatic sites (case 8 had metastases of lung and mediastinal lymph nodes; case 9 had metastases of thyroid and cervical lymph nodes). The median time from the diagnosis to metastasis was 9.4 years (range 1.1 to 13.8 years). The tumor cells were arranged in papillary, acinar, sheet, cluster or single scattered pattern. Most cases had uniform nuclei with mild atypia and inconspicuous nucleoli, while some cases had variable nuclei with prominent nucleoli. The cytoplasm of the tumor cells was abundant. Some cases showed clear cytoplasm with small vacuoles, while some of them showed eosinophilic and granular cytoplasm. Immunocytochemically, the tumor cells were positive for CKpan(AE1/AE3,6/6), PAX8 (9/9), CAⅨ (9/9), CD10 (9/9), and vimiten (8/8). Patients were treated primarily with targeted therapy and/or immunotherapy and curettage and radiation therapy for bone lesions. The follow-up time ranged from 1.0 month to 41.5 months (median, 20 months), and all patients survived at the end of follow-up.Conclusions:The cytology of metastatic CCRCC often shows uniform cell size, abundant and clear cytoplasm, low nuclear/cytoplasmic ratio, and mild nuclear atypia. Its cytological diagnosis is challenging because it occurs in various sites and needs to be differentiated from primary tumors of these sites. Emphasis should be placed on the morphological recognition of CCRCC, and immunocytochemical staining should be used to improve diagnosis. When necessary, molecular testing can be employed for diagnosis. Meanwhile, the medical history should be carefully inquired by pathologists to avoid missed diagnosis and misdiagnosis.