Growing genetic and pathological evidence has identified microglial dysfunction as a key contributor to the pathogenesis and progression of various neurological disorders, positioning microglia replacement as a promising therapeutic strategy. Traditional bone marrow transplantation (BMT) methods for replenishing brain microglia have limitations, including low efficiency and the potential for brain injury because of preconditioning regimens, such as irradiation or chemotherapy. Moreover, BM-derived cells that migrate to the brain do not recapitulate the phenotypic and functional properties of resident microglia. Here, we present a microglia transplantation strategy devoid of any conditioning, termed “tricyclic microglial depletion for transplantation” (TCMDT). This approach leverages three cycles of microglial depletion using the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX3397, creating an optimal window for efficient engraftment of exogenous microglia. Transplantation of primary cultured microglia by TCMDT successfully restored the identity and functions of endogenous microglia. To evaluate the therapeutic potential of TCMDT, we applied this strategy to two distinct mouse models of neurologic disorder. In a Sandhoff disease model, a neurodegenerative lysosomal storage disorder caused by hexosaminidase subunit beta ( Hexb ) deficiency, TCMDT effectively replaced deficient microglia, attenuating neurodegeneration and improving motor performance. Similarly, in an Alzheimer’s disease (AD)–related amyloid mouse model carrying the triggering receptor expressed on myeloid cells 2 (Trem2) R47H mutation, our transplantation strategy rescued microglial dysfunction and mitigated AD-related pathology. Overall, our study introduces TCMDT as a practical, efficient, and safe approach for microglia replacement, suggesting therapeutic potential for treating neurological disorders associated with microglial dysfunction.

Rationale: Osmotic demyelination syndrome (ODS) is a noninflammatory demyelinating disorder involving the pontis and other regions of the central nervous system. This article tries to enhance the understanding of ODS. Combined with clinical features, we use laboratory/imaging examination and literature review. Patient concerns: We report on 4 ODS cases and review the different etiologies, clinical manifestations, and possible pathophysiology. Diagnoses: We provide an update on the diagnosis and treatment of ODS, with a special focus on the prevention of ODS. Interventions: We corrected the hyponatremia appropriately and treated complications. Outcomes: The development of ODS is by association with a variety of clinical conditions. Also, the prognosis of ODS is heterogeneous, ranging from complete recovery to vegetative state, even death. However, there is no specific effective treatment, thus, it is more important to recognize the path mechanism of ODS and to avoid its occurrence. Lessons: It is essential to reduce the risk of suffering this potentially devastating disease through an appropriate rate of hyponatremia correction and the treatment of comorbid clinical conditions.

Objective: This study aims to evaluate the epidemiological features of sexual dysfunction in people aged more than 65 years in parts of China, and to investigate the independent significant risk factors. Methods: According to the population distribution of five communities in Xiamen and Chongqing, we have randomly enrolled 2403 people more than 65 years-of-age. We collected data information through a questionnaire survey. Then demonstrated the current condition of sexual dysfunction in the samples by statistical analysis, and multivariable logistic regression was used to disclose the risk factors of sexual dysfunction in the older adults. Results: According to this study, about 10.48% of the elderly had sexual dysfunctions of different degrees and duration. The proportion of men was about twice that of women (14.5% of males and 7.3% of females). During the course of the disease, 3.19% (43/1344) of women and 3.31% (35/1059) of men had more than 15 years duration of sexual dysfunction. In severity, 5.7% (77/1344) of women and 7.0% (74/1059) of men had very severe sexual dysfunction. There were statistically significant differences in BMI, smoking, drinking history, hypertension, depression incidence or median (p< 0.05). Alcohol consumption history [OR = 1.711, 95% CI: 1.124– 2.604, p = 0.012] and depression [OR = 2.107, 95% CI: 1.109– 4.356, p =0.044] were independent risk factors for sexual dysfunction. Conclusion: The prevalence of sexual dysfunction was low among elderly in the southern part of China. But the course of the disease is long and the degree of the disease is very severe. Elderly with a history of drinking and depression are more prone to sexual dysfunction.

Patients with growth hormone-secreting pituitary adenoma (GHPA) often fail to exhibit the molecular signatures typically associated with tumorigenesis. This study investigates the role of protein kinase C delta (PKCδ) in modulating cell apoptosis, migration, invasion, and tumor growth in pituitary adenoma. We assessed the activation of the PKA/CREB/ERK signaling pathway and cell apoptosis through RT-qPCR and western blot analysis. Wound-healing and transwell assays were employed to evaluate cell migration and invasion. Combined treatment with rottlerin and phorbol 12-myristate 13-acetate (PMA) reversed the inhibition of the PKA/CREB/ERK signaling pathway, downregulated cell apoptosis, and reduced growth hormone secretion in GH3 cells. A decrease in the level of PKCδ also inhibited the PKA/CREB/ERK signaling pathway, reduced cell apoptosis, and suppressed the secretion of growth hormone. Notably, growth hormone reversed the decline in cell migration and invasion following PKCδ siRNA treatment. Moreover, in nude mice with tumor models, growth hormone reversed the reduction in tumor volume induced by PKCδ siRNA. In conclusion, this study demonstrates that reducing PKCδ inhibits tumor growth by suppressing growth hormone via inhibition of the PKA/CREB/ERK signaling pathway.

BACKGROUND For children and adolescents, deliberate self-harm (DSH) is becoming a mental health problem of concern. Despite several studies on the prevalence and factors of DSH in the world, there is little information on DSH among children and adolescents in China. This study explores the prevalence, types, associated risk factors and tendency of DSH in pediatric psychiatric inpatients in China. AIM To understand the situation of DSH among hospitalized children and adolescents and its related factors. METHODS In this study, we retrospectively studied 1414 hospitalized children and adolescents with mental illness at Xiamen Mental Health Center from 2014 to 2019, extracted the demographic and clinical data of all patients, and analyzed clinical risk factors of DSH. RESULTS A total of 239 (16.90%) patients engaged in at least one type of DSH in our study. Cutting (n = 115, 48.12%) was the most common type of DSH. Females (n = 171, 71.55%) were more likely to engage in DSH than males (n = 68, 28.45%). DSH was positively associated with depressive disorders [OR = 3.845 (2.196-6.732); P < 0.01], female [OR = 2.536 (1.815-3.542); P < 0.01], parental marital status [OR = 5.387 (2.254-12.875); P < 0.01] and negative family history of psychiatric illness [OR = 7.767 (2.952-20.433); P < 0.01], but not with occupation, substance use and history of physical abuse. CONCLUSION Our findings suggest that for patients with depression, females, an abnormal marriage of parents, and no history of mental illness, attention should be paid to the occurrence of DSH.