Mitophagy-related genes could facilitate the development of septic shock during immune infiltration.

Septic shock often occurs following critically low blood pressure in patients with sepsis, and is accompanied by a high death rate. Although mitophagy is associated with infection and immune responses, its role in septic shock remains unknown. This study screened effective mitophagy-related genes (MRGs) for medical practice and depicted immune infiltration situations in patients with septic shock. Gene expression profiles of GSE131761 from the Gene Expression Omnibus database were compiled for differential analysis, weighted gene co-expression network analysis, and immune infiltration analysis, while other GSE series were used as validation datasets. A series of validation methods were used to verify the robustness of hub genes, while a nomogram and prognosis model were established for medical practice. Six genes were screened via combinations of differentially expressed genes, weighted gene co-expression network analysis, and MRGs. From this, 3 hub genes (MAP1LC3B, ULK1, and CDC37) were chosen for subsequent analysis based on different validation methods. Gene set enrichment analysis showed that leukocyte trans-endothelial migration and the p53 signaling pathway were abnormally activated during septic shock. Immune infiltration analysis indicated that the imbalance of neutrophils and CD4 naive T cells was significantly correlated with septic shock progression. A nomogram was generated based on MAP1LC3B, ULK1, and CDC37, as well as age. The stability of our model was confirmed using a calibration plot. Importantly, patients with septic shock with the 3 highly expressed hub genes displayed worse prognosis than did patients without septic shock. MAP1LC3B, ULK1, and CDC37 are considered hub MRGs in the development of septic shock and could represent promising diagnostic and prognostic biomarkers in blood tissue. The validated hub genes and immune infiltration pattern expand our knowledge on MRG functional mechanisms, which provides guidance and direction for the development of septic shock diagnostic and therapeutic markers.

A cutting-edge strategy for spinal cord injury treatment: resident cellular transdifferentiation.

Spinal cord injury causes varying degrees of motor and sensory function loss. However, there are no effective treatments for spinal cord repair following an injury. Moreover, significant preclinical advances in bioengineering and regenerative medicine have not yet been translated into effective clinical therapies. The spinal cord's poor regenerative capacity makes repairing damaged and lost neurons a critical treatment step. Reprogramming-based neuronal transdifferentiation has recently shown great potential in repair and plasticity, as it can convert mature somatic cells into functional neurons for spinal cord injury repair in vitro and in vivo, effectively halting the progression of spinal cord injury and promoting functional improvement. However, the mechanisms of the neuronal transdifferentiation and the induced neuronal subtypes are not yet well understood. This review analyzes the mechanisms of resident cellular transdifferentiation based on a review of the relevant recent literature, describes different molecular approaches to obtain different neuronal subtypes, discusses the current challenges and improvement methods, and provides new ideas for exploring therapeutic approaches for spinal cord injury.

Neuromuscular effect of dexmedetomidine on sevoflurane: an open-label, dose-escalation clinical trial.

BACKGROUND: Sevoflurane presents reliable central neuromuscular effects. However, little knowledge is available regarding the interaction between sevoflurane and demedetomidine. We evaluated the neuromuscular effect of dexmedetomidine on sevoflurane in patients with normal neuromuscular transmission and calculated the 50% effective concentration (EC50). METHODS: One-hundred and forty-four ASA grade I~II patients with normal neuromuscular transmission, aged 20~60 years old, undergoing lower limbs surgery were enrolled in this open-label, dose-escalation clinical trial. Patients were randomly assigned into 12 groups. Each patient received intravenous 0, 0.5, or 1.0 µg/kg dexmedetomidine 15 min after inhaling 0.7, 1.0, 1.4, or 2.0 MAC sevoflurane. Neuromuscular monitoring was recorded from the adductor pollicis muscle by using acceleromyography with train-of-four (TOF) stimulation of the ulnar nerve (2 Hz every 20 s). TOF ratio was recorded before inhaling sevoflurane, 15 min after keeping constant at target MAC of sevoflurane, 30 min after receiving target dose of dexmedetomidine, and 15 min after sevoflurane washing out. RESULTS: Sevoflurane produced a concentration-dependent decrease in TOF ratio. Mean TOF ratio in 0.7, 1.0, 1.4, and 2.0 MAC groups was 97.9%, 94.9%, 84.7%, and 77.2%, respectively. Neuromuscular EC50 of sevoflurane was 1.31 MAC (95% CI: 1.236~1.388 MAC). Intravenous 0.5 and 1.0 µg/kg dexmedetomidine decreased 3.1% (EC50: 1.27 MAC [95% CI: 1.206~1.327 MAC]) and 10.7% (EC50: 1.17 MAC [95% CI: 1.122~1.217 MAC]) of neuromuscular EC50, respectively. CONCLUSIONS: Sevoflurane has a concentration-dependent central neuromuscular effect in patients with normal neuromuscular transmission. Intravenous dexmedetomidine dose-dependently decreases the neuromuscular EC50 of sevoflurane.