Selective autophagy is an evolutionarily conserved mechanism that removes excess protein aggregates and damaged intracellular components. Most eukaryotic cells, including neurons, rely on proficient mitophagy responses to fine-tune the mitochondrial number and preserve energy metabolism. In some circumstances (such as the presence of pathogenic protein oligopolymers and protein mutations), dysfunctional mitophagy leads to nerve degeneration, with age-dependent intracellular accumulation of protein aggregates and dysfunctional organelles, leading to neurodegenerative disease. However, when pathogenic protein oligopolymers, protein mutations, stress, or injury are present, mitophagy prevents the accumulation of damaged mitochondria. Accordingly, mitophagy mediates neuroprotective effects in some forms of neurodegenerative disease (e.g., Alzheimer's disease, Parkinson’s disease, Huntington's disease, and Amyotrophic lateral sclerosis) and acute brain damage (e.g., stroke, hypoxic–ischemic brain injury, epilepsy, and traumatic brain injury). The complex interplay between mitophagy and neurological disorders suggests that targeting mitophagy might be applicable for the treatment of neurodegenerative diseases and acute brain injury. However, due to the complexity of the mitophagy mechanism, mitophagy can be both harmful and beneficial, and future efforts should focus on maximizing its benefits. Here, we discuss the impact of mitophagy on neurological disorders, emphasizing the contrast between the positive and negative effects of mitophagy.

Sepsis‐associated encephalopathy (SAE) has typically been associated with a poor prognosis. Although sestrin 2 (SESN2) plays a crucial role in metabolic regulation and the stress response, its expression and functional roles in SAE are still unclear. In the present study, SAE was established in mice through caecal ligation and puncture (CLP). The adeno‐associated virus 2 (AAV2)‐mediated SESN2 expression (ie overexpression and knockdown) system was injected into the hippocampi of mice with SAE, and subsequently followed by electron microscopic analysis, the Morris water maze task and pathological examination. Our results demonstrated an increase of SESN2 in the hippocampal neurons of mice with SAE, 2‐16 hours following CLP. AAV2‐mediated ectopic expression of SESN2 attenuated brain damage and loss of learning and memory functions in mice with SAE, and these effects were associated with lower pro‐inflammatory cytokines in the hippocampus. Mechanistically, SESN2 promoted unc‐51‐like kinase 1 (ULK1)‐dependent autophagy in hippocampal neurons through the activation of the AMPK/mTOR signalling pathway. Finally, AMPK inhibition by SBI‐0206965 blocked SESN2‐mediated attenuation of SAE in mice. In conclusion, our findings demonstrated that SESN2 might be a novel pharmacological intervention strategy for SAE treatment through promotion of ULK1‐dependent autophagy in hippocampal neurons.

To analyze the clinical features, laboratory findings, and imaging characteristics of severe Mycoplasma pneumoniae pneumonia (SMPP) in children, identify early warning indicators, and characterize macrolide-resistant M. pneumoniae pneumonia (MRMPP). Additionally, we developed and validated a nomogram model for predicting the risk of SMPP. This retrospective cohort study included children diagnosed with M. pneumoniae pneumonia (MPP) who were admitted to the West China Second Hospital of Sichuan University between September 2022 and February 2024. Data on demographics, clinical manifestations, laboratory results, and imaging findings were collected and analyzed. Compared to non-severe cases, children with SMPP had a significantly longer fever duration (8 days vs. 4 days, P < 0.001), higher peak body temperature (39.3 °C vs. 38.5 °C, P < 0.001), and a higher incidence of wheezing (13% vs. 0%, P < 0.05). There was no significant difference in macrolide resistance rates between the groups (P > 0.05). Radiological analysis revealed a higher frequency of pulmonary consolidation (69% vs. 0%, P < 0.001) and pleural effusion (22% vs. 7%, P = 0.031) in the SMPP cohort. LASSO regression identified eight key predictors: fever duration, peak body temperature, wheezing, extrapulmonary complications, hemoglobin levels, pulmonary consolidation, mosaic sign, and bronchial occlusion. The nomogram demonstrated excellent discriminative ability, with training and validation AUC values of 0.972 (95% CI 0.960–0.984) and 0.975 (95% CI 0.958–0.992), respectively. We developed and validated a nomogram for quantitative risk assessment of SMPP. This model can aid clinicians in the early identification of severe cases and in optimizing treatment strategies.

Exophiala dermatitidis is a relatively common environmental black yeast with a worldwide distribution that rarely causes fungal infection. Here, we report a case of a 6-year-old girl with central nervous system (CNS) encephalitis caused by E. dermatitidis and Angiostrongylus cantonensis. E. dermatitidis was identified by both cerebrospinal fluid culture and metagenomic next-generation sequencing (mNGS). Angiostrongylus cantonensis infection was confirmed by an enzyme linked immunosorbent assay (ELISA). Whole exome sequencing showed that this previously healthy girl carried a homozygous CARD9 mutation for c.820dupG (p.D274Gfs*61) that underlies invasive fungal and parasite infections. We chose glucocortieoid pulse therapy and anti-infective therapy based on the initial results of laboratory examination and cranial MRI images. With the aggravation of the disease and the evidence of the subsequent etiologic test, the combination of antifungal antiparasitic treatments (voriconazole, fluorocytosine and amphotericin B) were actively used. Unfortunately, the girl finally died due to severe systemic infection. mNGS performs a potential value for diagnosing rare CNS infections, and autosomal recessive CARD9 deficiency should be considered in patient with fatal invasive fungal infections.

Introduction: Drug-related problems (DRPs) refer to events or circumstances involving drug therapy that actually or potentially interfere with desired health outcomes. DRPs might be severe for children with chronic diseases managed at primary health care institutions, but the relevant research is scarce.Objective: In this cross-sectional study, we aimed to explore the prevalence, types, causes, and influencing factors of DRPs in children with chronic diseases in a Chinese primary health care institution.Methods: We recruited children with chronic diseases who visited the pediatric outpatient department in a primary health care institution from July 1 to 12 October 2021. Clinical pharmacists identified DRPs through medication therapy reviews, classified the types and causes of DRPs, and distinguished the manifested DRPs that affected the outcome and potential DRPs that were going to affect the outcome.Results: A total of 188 children with chronic diseases was included, and 584 DRPs were identified in 89.89% of participants. The most common type of DRPs was “treatment effectiveness” (a manifested problem or potential problem with the effect of the pharmacotherapy; 83.56%), of which 67.29% were potential DRPs. The second common type was “treatment safety” (patient suffers or could suffer from an adverse drug event; 14.21%), of which 89.16% were potential DRPs. The most common cause of DRPs was related to the process of use (42.24%), such as “patient uses/takes less drug than prescribed or does not take the drug at all,” “patient stores drug inappropriately,” and “patient administers/uses the drug in a wrong way.” The second common cause was related to the process of dispensing (29.83%), such as “necessary information not provided or incorrect advice provided” and “prescribed drug is not available.” The third common cause was related to the process of prescribing (26.21%), such as “drug dose is too low” and “no or incomplete drug treatment despite an existing indication.” The number of combined medications was an influencing factor for the frequency of DRPs (p < 0.05).Conclusion: This cross-sectional study showed that the current situation regarding DRPs among children with chronic diseases managed in the primary health care institution was serious. The types of DRPs were mainly related to treatment effectiveness, and improper usage of medications was one of the main causes of DRPs. The number of combined drugs was the influencing factor for the frequency of DRPs. In the future, pharmacists should consider formulating pharmaceutical intervention strategies for this specific group according to the characteristics of DRPs.

Central nervous system (CNS) aspergillosis has the characteristics of multifocality, polymorphism, and coexistence of pathological types, and missed diagnosis and misdiagnosis frequently occur at the initial stage. The thesis reports a rare case of infant infection of CNS aspergillosis with the first-episode of intracranial hemorrhage. An 11-month-old female infant suffered convulsion and coma two days after the onset of fever and emesis. Its cranial computed tomography (CT) displayed subdural hemorrhage in the left tentorium cerebelli and tests indicated normal cerebrospinal fluid (CSF). Three days after being hospitalized, the infant had difficulty breathing and its CT presents consolidation in the right lung. However, treatment with ceftriaxone (ivgtt) had no effect on the baby. The patient's bronchoalveolar lavage fluid (BALF) was cultured into Aspergillus spp, its galactomannan (GM) antigen in CSF counted 3.0, higher than that in BALF which counted 2.6, and cranial magnetic resonance imaging (MRI) revealed multiple ring reinforced tubercles in sulci. Hence it was clinically diagnosed with CNS aspergillosis. Voriconazole for intravenous injection. After the intravenous injection, its trough concentration was 4.2 μg/mL, and it was within the recommended range. After one week's treatment with voriconazole, the infant's consciousness was improved. Four weeks later, with normothermia and clear consciousness, the patient was discharged. With oral administration of voriconazole up to 16 weeks, its physical state suggests no relapse and cranial MRI indicated disappearance of nodules in sulci. CNS aspergillosis with first-episode of intracranial hemorrhage probably leads to misdiagnosis and GM test combined with cranial MRI can augment its accuracy in the early diagnosis.