Zhenming Kang

Sleep deprivation is a global health concern that disrupts hippocampal proteostasis and leads to cognitive decline. Heat shock protein 70 (HSP70), a key molecular chaperone supporting neuronal survival, is downregulated under sleep deprivation, yet its regulatory mechanisms remain unclear. A murine sleep deprivation model was established using the multiple-platform method. Cognitive performance was assessed with the Y-maze and novel object recognition tests. Western blotting, qRT-PCR, cycloheximide (CHX) chase, and coimmunoprecipitation assays were performed to examine the regulation of HSP70 by the E3 ligase UBOX5. In vivo, mice with UBOX5 knockout were treated with sleep deprivation, followed by behavioral testing and enzyme-linked immunosorbent assay measurement of hippocampal cytokines. Sleep deprivation produced a duration-dependent decline in memory and recognition, accompanied by reduced hippocampal HSP70 and increased UBOX5 expression. In vitro, UBOX5 overexpression decreased, whereas knockdown increased HSP70 protein abundance without altering transcript levels. CHX chase assays confirmed accelerated degradation, and coimmunoprecipitation demonstrated UBOX5-dependent, UBE2M-mediated polyubiquitination of HSP70. Knockout of UBOX5 attenuated sleep deprivation-induced cognitive impairment and neuroinflammation. UBOX5 destabilizes HSP70 via ubiquitination, promoting sleep deprivation-induced neuroinflammation and cognitive dysfunction. These findings support the UBOX5/HSP70 axis as a novel mechanistic link between sleep deprivation and neuronal injury, and a potential therapeutic target.

Chronic sleep deprivation impairs cognition and triggers neuroinflammation, but effective molecular therapies are lacking. Heat shock protein 70 (HSP70) offers neuroprotection, though its delivery across the blood–brain barrier remains a challenge. This study investigates exosomes as a vehicle to enhance brain delivery of HSP70 for treating chronic sleep deprivation. We engineered HEK293T cells to stably express HSP70 mRNA and the brain-targeting RVG-Lamp2b fusion protein, generating HSP70@Exo^RVG exosomes. These were characterized via transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. In vitro uptake and HSP70 expression were assessed in neural progenitor cells (NPCs). In vivo efficacy was evaluated in a sleep-deprived mouse model using behavioral tests and molecular analyses of inflammatory and neurotrophic markers. HSP70@Exo^RVG exosomes efficiently delivered HSP70 mRNA to NPCs, increasing intracellular HSP70 protein. In vivo, systemic administration restored memory performance, reduced hippocampal TNF-α, IL-6, and IL-1β levels, and increased IL-10. Treatment also elevated brain-derived neurotrophic factor and phosphorylated CREB, indicating enhanced neurotrophic signaling. These effects surpassed those of non-targeted or empty exosomes. Engineered exosomes enabled effective brain-targeted HSP70 mRNA delivery, reversing cognitive and inflammatory consequences of sleep deprivation. To our knowledge, this is the first demonstration of RVG-modified exosomes successfully delivering mRNA (rather than siRNA or miRNA) for the treatment of sleep deprivation–induced deficits. HSP70@Exo^RVG offers a promising, noninvasive therapeutic strategy for sleep-related neurodegenerative conditions and highlights the potential of exosome-based mRNA delivery systems.

Total hip arthroplasty (THA) is a common surgical treatment for advanced hip disorders, particularly in older adults. However, postoperative recovery in th

Ultrasound-guided transversus abdominis plane (TAP) block is widely used to provide effective postoperative analgesia and facilitate enhanced recovery after laparoscopic radical colectomy. However, the duration of TAP block is often limited by the pharmacokinetics of local anesthetics, and evidence regarding optimal adjuvant combinations to prolong its efficacy remains scarce. In this prospective, randomized controlled trial, 160 patients undergoing elective laparoscopic colectomy were randomly assigned to four groups (n = 40 each): Control (ropivacaine alone), Dexmedetomidine group (ropivacaine + dexmedetomidine), Dexamethasone group (ropivacaine + dexamethasone), and Combination group (ropivacaine + dexmedetomidine + dexamethasone). Primary outcomes included postoperative pain scores and sufentanil consumption. Secondary outcomes included Ramsay Sedation Scores, CD4+/CD8 + T cell ratios, and serum markers of stress response. Compared to ropivacaine alone, both dexmedetomidine and dexamethasone as single adjuvants significantly reduced postoperative pain scores and opioid requirements (p < 0.05). The combination group exhibited the most prolonged analgesic effect, with significantly lower sufentanil consumption and higher sedation scores at 6 and 24 h (p < 0.01). Moreover, both adjuvants attenuated the postoperative decline in CD4+/CD8 + T cell ratio, and the combination group demonstrated the greatest preservation of immune function and suppression of stress-induced immunosuppression. The combination of dexmedetomidine and dexamethasone as adjuvants to ropivacaine in TAP block provides superior and prolonged analgesia, reduces opioid consumption, and offers additional immunomodulatory benefits. This strategy represents a promising enhancement to multimodal analgesia protocols for patients undergoing laparoscopic colectomy. The study was registered in Chinese Clinical Trial Registry (ChiCTR2200065816, 2022-11-16).

Objectives: This study aimed to identify the contributing factors, including systemic immune-inflammation index (SII), for pulmonary infections in elderly patients undergoing laparoscopic abdominal surgery with tracheal intubation under general anesthesia.Methods: A total of 356 eligible elderly patients were monitored post-surgery for pneumonia. Pathogens were identified from sputum samples, and factors like age, smoking, chronic obstructive pulmonary disease (COPD), intubation, anesthesia duration, and SII were analyzed for their influence on infection risk.Results: The pathogens were predominantly Gram-negative bacteria, with Klebsiella pneumoniae being the most common (26%). Significant risk factors for developing pneumonia included advanced age, smoking, COPD, prolonged intubation, and extended anesthesia. A higher preoperative SII was associated with an increased risk of pneumonia and correlated with infection severity and elevated levels of inflammatory markers. Multivariate analysis identified age over 70 (OR = 1.273, p = 0.021), age over 80 (OR = 2.085, p < 0.001), COPD (OR = 1.528, p = 0.009), prolonged intubation >2 h (OR = 2.187, p < 0.001), general anesthesia >4 h (OR = 1.846, p = 0.006), operative time > 2 h (OR = 1.415, p = 0.016), and preoperative SII >489.3 (OR = 1.403, p = 0.012) as independent risk factors for postoperative pulmonary infection.Conclusion: Our study highlighted critical risk factors for postoperative pulmonary infections in elderly patients undergoing laparoscopic abdominal surgery. Preoperative SII could be a novel predictor, offering potential for improved pre-surgical risk assessment.

Background: Single-lung ventilation (SLV) is a widely used procedure in thoracic surgery; however, it can lead to hypoxemia, which is attributed to intrapulmonary shunt and hypoxic pulmonary vasoconstriction. Stellate ganglion blockade (SGB) has shown protective effects during SLV in various pulmonary conditions. The objective of the study was to assess the clinical utility of ultrasound-guided SGB in patients undergoing thoracoscopic pulmonary lobectomy through a prospective clinical trial.Methods: This prospective randomized controlled double-blind trial included 116 patients who underwent SLV. After exclusion, 88 patients were randomly assigned to either the SGB group (n = 40) or control group (n = 39), with the latter receiving no SGB. Hemodynamics using oxygenation index (OI) and the pulmonary shunt fraction (Qs/Qt), respiratory mechanics using dynamic lung compliance (Cdyn) and mean airway pressure (P_mean), and levels of pro-inflammatory factors (IL-6 and IL-8) were assessed as clinical outcomes after surgery.Results: SLV induced upregulation of P_mean, Qs/Qt, and levels of IL-6 and IL-8 and downregulation of Cdyn and OI. Compared to the control group, the SGB group demonstrated significantly decreased P_mean, Qs/Qt, IL-6, and IL-8 and increased Cdyn and OI, suggesting the protective effects of SGB in patients who received SLV.Conclusions: Ultrasound-guided SGB improves respiratory mechanics, hemodynamics, and inflammatory responses during SLV. Our findings suggest a protective role of SGB in reducing complications associated with SLV.Clinical Trial Registration: The study was registered in the Chinese Clinical Trial Registry (#ChiCTR2200063210).