Aim: To review information resources on this problem for the provision of modern knowledge in the pathogenesis of this pathology. Materials and Methods: An analysis of data from literary sources and medical articles in Pub Med was carried out in order to clarify the influence of cortisol and testosterone on the development of metabolic syndrome. The search was conducted over the last 5 years, but there is material from 2001, 2018, and 2019. Total volume of the number of sources: 17. Conclusions: The metabolic syndrome (MetS) is a collection of abnormalities that predispose individuals to diabetes, atherosclerosis, and cardiovascular disease (CVD). Patients with metabolic syndrome exhibit hyperactivity of the hypothalamic-pituitary-adrenal (HPA) system, resulting in «functional hypercorticism.» Stress is thought to play a significant role in this interaction by increasing the sensitivity of the hypothalamic-pituitary-adrenal axis. The enzyme 11-betahydroxysteroid dehydrogenase type 1 (11HSD1), which is involved in glucocorticoid metabolism in peripheral tissues (particularly adipose tissue and liver), has been implicated in metabolic syndrome and central obesity. Overexpression of 11HSD1 in adipocytes is observed in metabolic syndrome and central obesity, leading to increased conversion of cortisone to cortisol and excessive tissue-specific glucocorticoid activity.

Chimeric antigen receptor T-cell (CAR-T) therapies targeting CD19 have revolutionized the treatment of B-cell malignancies, but their use is frequently complicated by immune effector cell-associated neurotoxicity syndrome (ICANS). The underlying mechanisms include endothelial dysfunction, blood–brain barrier disruption, and neuroinflammation. Circulating biomarkers of neuronal and astroglial injury, such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), may provide insight into ICANS pathophysiology and serve as predictive tools. We conducted a retrospective study of 34 adult patients treated with anti-CD19 CAR-T cells for B-cell malignancies. Serum NfL and GFAP were measured at infusion (day 0) and day 7 using ultrasensitive immunoassays. Baseline GFAP and NfL levels correlated with endothelial activation markers, including mEASIX and lactate dehydrogenase, but not with demographic variables. ICANS of any grade occurred in 34% of patients, and baseline levels of both GFAP and NfL were significantly associated with ICANS development and with steroid requirement. In contrast, changes in biomarker concentrations between day 0 and day 7 were not statistically significant overall, although individual variability was observed. At day 7, elevated NfL levels correlated with laboratory evidence of disseminated intravascular coagulation (DIC), prolonged clotting time, and C-reactive protein elevation. GFAP elevation was also linked to coagulopathy, particularly prolonged clotting time. Baseline serum levels of GFAP and NfL predict the risk of ICANS and the need for corticosteroid intervention in CAR-T-treated adults, supporting their role as biomarkers of pre-existing neuronal susceptibility. Furthermore, their association with coagulation abnormalities underscores the interplay between neurotoxicity, endothelial stress, and systemic inflammation. These findings highlight the potential clinical utility of integrating GFAP and NfL into multimodal biomarker panels to improve risk stratification and management of CAR-T neurotoxicity.

Smith-Lemli-Opitz syndrome (SLOS) is a rare, autosomal recessive disorder characterized by congenital malformations, intellectual disability, and behavioral abnormalities. SLOS results from mutations in the DHCR7 gene, leading to impaired cholesterol biosynthesis due to dysregulation of 7-dehydrocholesterol reductase. Cholesterol plays crucial roles in neurophysiology, including synaptic formation and neurotransmitter receptor regulation, which likely contribute to neurological manifestations in SLOS patients. While astrocytes are the main cholesterol producing cells in the brain, their specific role in SLOS pathogenesis remains unclear. In this study, we utilized induced pluripotent stem cell (iPSC)-derived astrocytes from a SLOS patient with DHCR7 c.C278T mutation and the isogenic control. We found decreased lipid droplet formation in SLOS iPSC astrocytes compared to controls, accompanied with diminished efflux of cholesterol and apolipoprotein E. Lipidomics revealed reduced cholesterol and cholesterol esters, as well as altered profiles of other lipids in SLOS iPSC astrocytes. While RNA-sequencing identified various genes and pathways affected by the disease status, those related to mitochondria functions were top-ranked. Mitochondrial electron transport chain oxidative phosphorylation gene expression decreased in SLOS iPSC astrocytes, alongside impaired mitochondrial respiration. Furthermore, SLOS iPSC astrocytes less effectively mediated neuroprotection on iPSC neurons than control astrocytes in serum-starvation conditions. SLOS iPSC astrocytes also poorly contributed to synaptic networks when co-cultured with iPSC neurons. Overall, our findings provide mechanistic insights into how DHCR7 disruption impacts astrocyte function, contributing to SLOS neuropathology by dysregulating lipid metabolism, mitochondrial respiration, and impaired neuroprotection.

This case report describes the diagnostic and therapeutic management of a 67-year-old female with a 40-year history of Sjögren disease (SjD) who was hospitalized for evaluation of recurrent fever lasting over one month. The patient' s initial diagnosis of SjD was established four decades earlier based on clinical manifestations, serological findings, and evidence of glandular damage. Her clinical presentation included recurrent parotid gland enlargement accompanied by sicca symptoms, notably persistent xerostomia and xerophthalmia, followed by progressive dental caries. Serological studies demonstrated positivity for antinuclear antibodies, anti-SSA/Ro, and anti-α-fodrin antibodies. Objective assessments confirmed significant ocular involvement (Schirmer' s test ≤5 mm/5 min) and pulmonary interstitial changes on chest CT, consistent with the 2016 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria for SjD. The patient' s condition remained stable under low-dose corticosteroids and disease-modifying anti-rheumatic drugs (DMARDs) until the recent onset of prolonged fever, necessitating evaluation for fever of unknown origin. Differential diagnoses considered disease flare, infection, and malignancy. The European Sjögren' s Syndrome Disease Activity Index (ESSDAI) score was 5 points, indicating moderate systemic disease activity. Initial laboratory investigations revealed no evidence of infection, and empirical anti-infective therapy proved ineffective. Notably, despite the absence of lymphadenopathy, laboratory findings including borderline positive IgM λ M-protein, elevated lactate dehydrogenase, hyperferritinemia, and increased β2-microglobulin levels raised suspicion for lymphoproliferative disorders, given the established association between SjD and lymphoma. Bone marrow aspiration showed no significant abnormalities, but PET/CT imaging detected hypermetabolic lesions in the left breast and right distal femur, suggesting potential malignancy. Subsequent histopathological examination of the breast lesion confirmed non-Hodgkin' s lymphoma (NHL), specifically diffuse large B-cell lymphoma (DLBCL) of the germinal center B-cell (GCB) subtype. Treatment with R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) induced complete metabolic remission after three cycles. However, she subsequently developed treatment-related complications, including myelosuppression and pulmonary infection. This case underscores the importance of maintaining a high index of suspicion for atypical site involvement in SjD patients, particularly when lymphoma risk factors are present. Comprehensive differential diagnosis should include lymphoma and other malignancies, and the diagnostic value of PET/CT and histopathological examination in disease evaluation is emphasized. SjD complicated by breast lymphoma is exceptionally rare, and its pathogenesis may involve lymphocytic infiltration, abnormal activation of lymphocytes, formation of ectopic germinal centers in the breast, and eventual malignant transformation. These mechanisms require further investigation through clinical and basic research studies. 报告1例67岁女性干燥综合患者并发乳腺淋巴瘤的诊疗经过。患者干燥综合征病史40余年，病情稳定，近1月余出现不明原因发热，实验室检查示免疫球蛋白M λ型M蛋白(血)可疑阳性，乳酸脱氢酶、铁蛋白、β2微球蛋白升高，高度警惕淋巴瘤可能，查体未触及体表淋巴结肿大，骨髓穿刺未见明显异常。正电子发射计算机体层成像(positron emission tomography-computed tomography，PET/CT)显示左乳和右股骨远端高代谢病灶，考虑恶性病变可能性大，鉴别乳腺癌伴骨转移或淋巴瘤等。经乳腺穿刺活检确诊为弥漫性大B细胞淋巴瘤，经R-CHOP化疗缓解。本病例提示对于具有淋巴瘤高危因素的干燥综合征患者，需重视不典型部位肿块的性质鉴别，警惕结外淋巴瘤的可能；PET/CT联合穿刺活检在诊断、鉴别诊断及病情评估中具有重要价值。

Biallelic pathogenic variants in DHCR7 result in decreased activity of 7-dehydrocholesterol (7-DHC) reductase, which converts 7-DHC to cholesterol, and causes Smith-Lemli-Opitz syndrome (SLOS). Elevated serum 7-DHC levels are indicative of SLOS as are intellectual disability (ID), growth retardation, microcephaly, craniofacial anomalies, and 2-3 toe syndactyly. Additional congenital malformations may be present in SLOS, and broad clinical variability has been recognized in SLOS. Rarely, biallelic pathogenic DHCR7 variants were reported with low-normal and normal intelligence quotient (IQ) and development. We report here a pair of siblings with mild global developmental delay, infrequent epileptic seizures, and elevated serum 7-DHC levels, associated with the homozygous DHCR7 variant c.988G>A (p.Val330Met). Remarkably, neither sibling displayed congenital anomalies nor dysmorphisms. Quattro-exome sequencing performed for global delay and mild ID in both siblings did not identify other ID causes. c.988G>A affects a highly conserved amino acid and displays a relatively high global population allele frequency of 0.04%, with absence of homozygotes from the population database gnomADv4.1.0. Our observation leads us to suggest that DHCR7 variant c.988G>A and other DHCR7 variants might be generally considered as underlying non-syndromic ID.