Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
Animals ; Autophagy/physiology* ; Oligodendroglia/metabolism* ; Myelin Sheath/physiology* ; Aging/pathology* ; Myelin Basic Protein/metabolism* ; Cell Lineage/physiology* ; Mice ; Oligodendrocyte Precursor Cells ; Mice, Inbred C57BL ; Brain/cytology* ; Cells, Cultured ; Cell Count

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective We aimed to evaluate the clinical efficacy of promoting blood circulation and eliminating phlegm method in preventing and treating patients with hydrocephalus after acute intracerebral hemorrhage.Methods This study included 139 patients with acute intracerebral hemorrhage who visited Affiliated Hospital of Chengdu University of Traditional Chinese Medicine,Guangyuan Hospital of Traditional Chinese Medicine,Affiliated Hospital of North Sichuan Medical College,Meishan Hospital of Traditional Chinese Medicine,and Xuyong Hospital of Traditional Chinese Medicine from September 2019 to June 2023.Patients who met the exposure factors of"using the method of promoting blood circulation and eliminating phlegm"were classified into the integrated Chinese and Western medicine cohort,while those who did not meet the exposure factors were classified into the Western medicine cohort.Clinical efficacy,incidence of hydrocephalus after intracerebral hemorrhage,sum of maximum distance between the anterior horn of the lateral ventricle and the head of the caudate nucleus(Huckman value),size of the hematoma,incidence of endpoint events,National Institutes of Health Stroke Scale(NIHSS)score,Modified Rankin Scale(mRS)score,and Barthel index score between two cohorts were compared.Results Total clinical effective rates for patients with hydrocephalus in the two cohorts were 60.0%and 75.0%,respectively.The total effective rate of the integrated Chinese and Western medicine cohort was higher than that of the Western medicine cohort(P<0.05).After 28 days of treatment,the incidence of hydrocephalus in patients in the integrated Chinese and Western medicine cohort was lower than that of the Western medicine cohort,and the Huckman value decreased compared with the Western medicine cohort(P<0.05).Compared with 24 hours after onset,both cohorts showed a reduction in hematoma size after 28 days of treatment;compared with the Western medicine cohort,patients in the integrated Chinese and Western medicine cohort had reduced hematoma size(P<0.05).After 6 months of onset,the number of deaths in the integrated Chinese and Western medicine cohort decreased compared with the Western medicine cohort(P<0.05).Compared with 28 days of treatment,the NIHSS and mRS scores of the patients in both cohorts decreased after 6 months,while the Barthel index score increased;compared with the Western medicine cohort,patients in the integrated Chinese and Western medicine cohort showed a decrease in the NIHSS and mRS scores after both 28 days of treatment and 6 months,while the Barthel index score increased(P<0.05).Conclusion Promoting blood circulation and eliminating phlegm can effectively prevent and treat hydrocephalus after intracerebral hemorrhage and does not increase the risk of bleeding within 24 hours.

The development status of medical device industry in Jilin Province was described,and the main problems during the development of medical device industry in Jilin Province was analyzed.Some countermeasures were put forward including enlarging the industrial scale,constructing business incubators in the field of medical device,guaranteeing the market access of the products,accelerating the registration and approval,strengthening the cross-discipline construction and forming medical-industrial institutes.References were provided for the development of medical device industry in Jilin Province.[Chinese Medical Equipment Journal,2024,45(7):67-71]

OBJECTIVE To study the immunotherapeutic effect of chimeric virus-like particles(VLPs) based on hepatitis E virus(HEV) against human papillomavirus type 16(HPV 16) tumor. METHODS HPV16 E7 was inserted into the p239 protein of HEV to form the recombinant chimeric protein p239-HPV16 E7. The constructed recombinant protein was expressed by Escherichia coli, purified, and then refolded, and the protein was detected by electron microscopy and dynamic light scattering to confirm size and shape. Then, the C57B/L mice were immunized with the protein grain, and the lymphocyte differentiation of mouse spleen was detected by flow cytometry and enzyme-linked immune spot immunoassay; in addition, TC-1 tumor cells were used to construct tumor models in C57B/L mice to evaluate the anti-tumor immune effect of protein particles in mice. RESULTS After refold in vitro, the structure of chimeric protein was observed under electron microscopy, and the size of particle was 22.80 nm. The obtained protein particles induced favorable specific cellular immune response in C57B/L mice. Compared with the control group, the proportions of CD3+/CD4+ and CD3+/CD8+ in spleen lymphocytes of experimental groups were significantly different(P＜0.05), and effector T cells secreting IFN-γ interferon were also increased remarkably. At the same time, the obtained protein particles could effectively inhibit the growth of tumor cells in TC-1 tumor-bearing mice, and the mice did not die during the experimental period, while the tumors in the control mice grew rapidly and all died after 6 weeks. CONCLUSION Chimeric protein p239-HPV16E7 which was expressed in prokaryotes can form virus-like particles and effectively induce anti-tumor immunity against HPV16.

Aim To study the inhibitory effect of attenuated salmonella SGN1, overexpressing methioninase, on nasopharyngeal carcinoma (NPC) and the underlying mechanism. Methods The cell proliferation, cell cycle, cell apoptosis, clony formation and migration a-bility of 5-8F, HNE-2, CNE-2 cells were measured u-sing flow cytometry assay, clone formation assay, and wound assay after the methionine restriction treatment. 5-8F, HNE-2, CNE-2 cells were infected with SGN1 at the multiplicity of infection (MOI) of 1: 100 for 5 hours, followed with the measurement of cell growth. A xenograft model was constructed by subcutaneous injection of 5-8F cells in mice to observe the inhibitory effect of SGN1 on nasopharyngeal carcinoma. Results Compared with the control group, methionine restriction significantly inhibited the proliferation, migration ability, and clone formation of nasopharyngeal carcinoma cells and blocked the G

Adipocyte enhancer binding protein 2, as a component protein of Polycomb repressive complex (PRC2), is involved in the proliferation and migration of many tumor cells. However, its role in HCC is still unclear. In this study, we identify that AEBP2 was upregulated in HCC samples from the UALCAN and Kaplan-Meier Plotter database, which was correlated to the overall survival time of HCC patients. Real-time quantitative PCR and Western blotting confirmed that the expression of AEBP2 in HCC cells was higher than normal liver cells. After silencing AEBP2 in HepG2 and Huh-7 cells, the effects of the proliferation, apoptosis, migration and invasion were detected by colony formation, CCK-8, flow cytometry, scratch healing and Transwell chamber, respectively. Compared with the control group, down-regulation of AEBP2 expression inhibited the proliferation, migration and invasion in HepG2 and Huh-7 cells, as well as promoted apoptosis (P<0. 05). Immunofluorescence and Western blotting results showed that AEBP2 silencing inhibited epithelial-mesenchymal transformation (EMT) (P < 0. 05). Bioinformatics analysis showed that AEBP2 is involved the PI3K/Akt signaling pathway. Western blotting results confirmed that silencing AEBP2 down-regulated the expression levels of PI3K, p-AKT (S473), mTOR, MMP-2 and MMP-9 proteins (P<0. 05). In addition, the effects of AEBP2 silencing on HepG2 cells migration and invasion could be reversed by PI3K/Akt pathway agonist insulin-like Growth Factors (IGF-1) (P < 0. 01). In summary, our study showed that AEBP2 promoted the proliferation and migration of HCC cell by regulating PI3K/AKT pathway. This study provided a theoretical basis for the role of AEBP2 in HCC.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*