Olanzapine is an atypical antipsychotic drug and a potent muscarinic M3 receptor (M3R) antagonist. Olanzapine has been reported to cause metabolic disorders, including dyslipidemia. Anaplastic lymphoma kinase (Alk), a tyrosine kinase receptor well known in the pathogenesis of cancer, has been recently identified as a key gene in the regulation of thinness via the regulation of adipose tissue lipolysis. This project aimed to investigate whether Olanzapine could modulate the hepatic Alk pathway and lipid metabolism via M3R. Female rats were treated with Olanzapine and/or Cevimeline (an M3R agonist) for 9 weeks. Lipid metabolism and hepatic Alk signaling were analyzed. Nine weeks’ treatment of Olanzapine caused metabolic disturbance including increased body mass index (BMI), fat mass accumulation, and abnormal lipid metabolism. Olanzapine treatment also led to an upregulation of Chrm3, Alk, and its regulator Ptprz1, and a downregulation of Lmo4, a transcriptional repressor of Alk in the liver. Moreover, there were positive correlations between Alk and Chrm3, Alk and Ptprz1, and a negative correlation between Alk and Lmo4. However, cotreatment with Cevimeline significantly reversed the lipid metabolic disturbance and adipose tissue accumulation, as well as the upregulation of the hepatic Alk signaling caused by Olanzapine. This study demonstrates evidence that Olanzapine may cause metabolic disturbance by modulating hepatic Alk signaling via M3R, which provides novel insight for modulating the hepatic Alk signaling and potential interventions for targeting metabolic disorders.

Background: Emerging evidence suggests that disrupted tryptophan (TRP) metabolism may contribute to an increased risk of neurodevelopmental disorders (NDDs) in the context of maternal inflammation, with gut microbiota playing a pivotal role in regulating TRP metabolic pathways.Methods: Juvenile female rats prenatally exposed to polyriboinosinic-polyribocytidylic acid (Poly I:C) were used to investigate the association between TRP metabolite disturbance and neuropathological/behavioral abnormalities. Behavioral tests assessed anxiety-like behavior, social interaction, and spatial memory. Immunohistochemical and gene expression analyses were performed on the prefrontal cortex (PFC) to evaluate microglial activation and neuroinflammation. TRP-kynurenine (KYN) pathway activity was measured in both PFC and peripheral circulation, along with intestinal TRP metabolism. Gut microbial composition was analyzed through diversity metrics and specific taxa identification.Results: Prenatal Poly I:C exposure induced anxiety-like behavior, impaired social interaction, and spatial memory deficits in offspring. The PFC showed sustained microglial activation and chronic neuroinflammation. TRP-KYN pathway activation was observed in both central and peripheral systems, accompanied by significant disruptions in intestinal TRP metabolism. Gut microbial analysis revealed reduced diversity and specific alterations in TRP-related taxa (Ruminococcus gauvreauii_group and Candidatus Saccharimonas). These microbial changes correlated with both intestinal TRP metabolic levels and behavioral abnormalities.Conclusion: Our findings demonstrate that aberrant TRP metabolism associated with gut microbiota dysbiosis contributes to neuroinflammation and behavioral deficits in offspring following prenatal immune activation, highlighting the gut-microbiota-TRP axis as a key mechanism in neurodevelopmental impairments.

Pediatricians commonly use the complete blood count (CBC) of capillary blood to evaluate health status, guide diagnoses, and determine treatment strategies. This study aimed to establish sex- and age-specific reference intervals (RIs) for 23 capillary CBC parameters for urban preschoolers in Fuzhou, Southeast China. Capillary blood CBC data of 18,369 healthy preschoolers who underwent annual physical examinations at Fujian Maternity and Child Health Hospital between January 01, 2022, and November 31, 2023, were analyzed retrospectively. To fully validate the new RIs, the data of all apparently healthy children within the same age cohort at the same institution were comprehensively analyzed in December 2023. The new RIs were assessed by comparing them with the RIs currently used in laboratories and those obtained from different regions, sample types, or methodologies. Dynamic temporal changes that differ between males and females were observed in the blood system of 3-7-year-old children in this region. The new sex- and age-specific RIs for capillary CBC parameters were feasible to guide clinical decision-making in the local region. Our findings demonstrated the importance of establishing sex- and age-specific RIs for each region and underscored the necessity of continuous adjustment of clinical Rls based on statistical rules and clinical responses.

Clinical serum biochemistry is used to assess maternal and fetal health; however, it involves complex physiological adaptations during fetal development, c

Background: Beyond the well-known metabolic side effects of second-generation antipsychotics (SGAs), recent studies suggest that neurodevelopmental disorders (NDDs) themselves confer an underlying susceptibility to metabolic dysregulation. However, it remains unclear whether a combined effect exists between SGAs and the NDD condition regarding metabolic syndrome, and which NDD-related pathophysiological changes contribute to metabolic disturbance. Methods: This study applies a translational framework combining retrospective clinical data from drug-naïve children with NDDs and a prenatal polyinosinic:polycytidylic acid (Poly I:C) rat model. Results: Baseline variations in lipid and glucose disturbances were observed in both cohorts, and these metabolic imbalances were further increased in adult female rats following long-term olanzapine or risperidone treatment, with significant interaction effect between Poly I:C and SGA observed for HOMA-IR. Moreover, the significant effects of both Poly I:C and SGAs on adipokines (leptin and adiponectin) and locomotor activity, with SGA-driven changes in insulin and prolactin, indicate that altered locomotion and divergent endocrine modulation serve as candidate pathways contributing to NDD-related metabolic risk. Discussion: These results highlight that NDD-related locomotor and endocrine changes should be considered as potential biological factors when finding effective strategies for preventing metabolic events during SGAs medication. These results underscore the clinical importance of metabolic monitoring in pediatric psychopharmacology, even prior to pharmacologic exposure.

To investigate the clinical characteristics of invasive non-typhoidal Salmonella (iNTS) infection in children and systematically analyze associated factors. Clinical data, including epidemiological information, demographic characteristics, clinical manifestations, laboratory test results, bacterial strain characteristics, and antimicrobial susceptibility profiles, were collected from pediatric patients hospitalized with non-typhoidal Salmonella (NTS) infection at Fujian Maternal and Child Health Hospital or Fujian Children's Hospital from January 2013 to December 2022. Patients were categorized into iNTS and non-iNTS infection groups based on bacterial culture sources. Univariate comparisons explored clinical features associated with iNTS infection. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses identified associated factors for iNTS infection. Subgroup analysis was performed by age stratification (infants: <1 year, toddlers: 1-<3 years, and older children: ≥3 years). A total of 314 children with NTS infection were included, of whom 38 (38/314, 12.1%) had iNTS infection. Disease onset was predominantly observed in infants and young children, with higher incidence during summer and autumn. Univariate and multivariate logistic regression analyses identified pre‑hospitalization fever duration (P<0.001, OR = 1.235, 95%CI 1.122-1.359), LDH level (P = 0.027, OR = 1.003, 95%CI 1.000-1.006), and Salmonella serogroup C1 (P = 0.013, OR = 4.392, 95%CI 1.373-14.049) as independent risk factors for iNTS infection. The combined ROC curve of these three factors showed an area under the curve (AUC) of 0.831, sensitivity of 76.3%, and specificity of 75.4%. In the infant subgroup, pre‑hospitalization fever duration (P = 0.006, OR = 1.205, 95%CI 1.055-1.376) and anemia (P = 0.039, OR = 2.884, 95%CI 1.053-7.897) were significantly associated with iNTS infection, yielding a combined AUC of 0.838. In hospitalized pediatric patients with NTS infection, pre‑hospitalization fever duration, LDH level, and Salmonella serogroup C1 are independent factors associated with iNTS infection, with good diagnostic performance (AUC = 0.831). In infants, anemia is also independently associated (combined AUC = 0.838). Epidemiological data, demographic characteristics, clinical manifestations, and routine laboratory tests provide preliminary clinical clues; however, further prospective studies are needed.