Global cerebral ischemia induced by cardiac arrest usually leads to poor neurological outcomes. Numerous studies have focused on ways to prevent ischemic damage in the brain, however clinical therapies are still limited. Our previous studies revealed that delta opioid receptor (DOR) activation with [d-Ala2, d-Leu5] enkephalin (DADLE), a DOR agonist, not only significantly promotes neuronal survival on day 3, but also improves spatial memory deficits on days 5-9 after ischemia. However, the neurological mechanism underlying DADLE-induced cognitive recovery remains unclear. This study first examined the changes in neuronal survival in the CA1 region at the advanced time point (day 7) after ischemia/reperfusion (I/R) injury and found a significant amelioration of damaged CA1 neurons in the rats treated with DADLE (2.5 nmol) when administered at the onset of reperfusion. The structure and function of CA1 neurons on days 3 and 7 post-ischemia showed significant improvements in both the density of the injured dendritic spines and the basic transmission of the impaired CA3-CA1 synapses following DADLE treatment. The molecular changes involved in DADLE-mediated synaptic modulation on days 3 and 7 post-ischemia implied the time-related differential regulation of PKCα-MARCKS on the dendritic spine structure and of BDNF- ERK1/2-synapsin I on synaptic function, in response to ischemic/reperfusion injury as well as to DADLE treatment. Importantly, all the beneficial effects of DADLE on ischemia-induced cellular, synaptic, and molecular deficits were eliminated by the DOR inhibitor naltrindole (2.5 nmol). Taken together, this study suggested that DOR activation-induced protective signaling pathways of PKCα-MARCKS involved in the synaptic morphology and BDNF-ERK-synapsin I in synaptic transmission may be engaged in the cognitive recovery in rats suffering from advanced cerebral ischemia.

Prior studies have indicated that the neuroprotective effects of dexmedetomidine (DEX) in cerebral ischemia, yet its mechanisms remain elusive. Using multi-omics approaches (RNA-seq, metabolomics, and single-cell RNA-seq), we discovered that DEX pretreatment significantly reduced cerebral infarct volume and improved neurological function in middle cerebral artery occlusion (MCAO) mice compared to PBS controls. Single-cell analysis revealed that DEX preserved microglial phagocytic function via metabolic regulation, leading to reduced microglial apoptosis and attenuated immune dysregulation—including decreased chemotactic neutrophils, B cells, and antigen-presenting fibroblasts. These cellular changes were corroborated by transcriptomic and metabolic profiles showing suppressed apoptosis and inflammation. Mechanistically, we identified HK2 (hexokinase 2) as a key regulator of microglial homeostasis, with its expression correlating with microglial migration, proliferation, and inflammation, findings validated in oxygen–glucose deprivation models. Collectively, our results demonstrate that DEX protects against cerebral ischemia–reperfusion injury by maintaining immune microenvironment homeostasis through microglial metabolic reprogramming mediated by HK2. This multi-omics study provides mechanistic insights supporting DEX’s translational potential in ischemic stroke therapy.

BACKGROUND Older patients often experience thirst after general anesthesia for gastrointestinal surgery, particularly during the post-anesthesia care unit (PACU) phase. Thirst not only compromises patient comfort but also induces anxiety, which may hinder recovery. Although previous studies have addressed postoperative thirst, research specifically examining thirst experiences and nursing needs in older patients remains limited. AIM To explore thirst experiences and nursing needs of older PACU patients following gastrointestinal surgery, aiming to inform targeted interventions. METHODS This study employed a phenomenological approach within a qualitative research framework. A purposeful sampling method was used to select 12 older patients who underwent gastrointestinal surgery under general anesthesia at a tertiary hospital in Shanghai between November and December 2024. Data were collected through semi-structured interviews and analyzed using Colaizzi’s seven-step method. Themes were extracted from the interview data. RESULTS Analysis of the interview data identified four main themes and eight subthemes: (1) Intense sensations of thirst post-surgery (subjective experience of thirst and duration of thirst); (2) Emotional experiences of thirst-related discomfort (anxiety, irritability, and helplessness); (3) Practical challenges in relieving thirst (limitations of current interventions and nursing response time); and (4) Patient expectations of nursing care (desire for more timely interventions and expectation for more proactive attention from nursing staff). CONCLUSION Older patients frequently experience substantial thirst discomfort after gastrointestinal surgery under general anesthesia. A multidisciplinary perioperative intervention plan is essential to alleviate these symptoms and enhance postoperative comfort.

Aim Renal fibrosis (RF) is a common clinical condition leading to irreversible renal function loss. Tyrosine kinase proteins and microRNAs (miRs) are associated with pathogenesis and we aim to investigate the role of Fer and its partner miR(s) in RF. Method In silico reproduction of Mouse Kidney FibrOmics browser was performed to identify potential miR(s) and target gene(s). In vivo validation was performed in C57BL/6 mice with unilateral ureteral obstruction (UUO). In vitro validation was performed in rat kidney fibroblast NRK-49F cells. Mimics and inhibitors of miR-29c-3p were constructed. The target gene Fer was monitored by RT-PCR and western blotting. The levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in serum and media were measured by ELISA. Results The Fer expression and protein level were gradually increased during 14 days of UUO modeling. miR-29c-3p expression was strongly correlated with that of Fer. In vivo validation showed increased expressions of fibrosis-associated genes and increased phospoho-Smad3 level in the UUO model. Fer-knockdown (KD) significantly decreased expressions of fibrosis-associated genes. Pharmaceutical inhibition of Fer showed similar effects to miR-29c-3p, and miR inhibition showed a significant decrease of excretion of inflammatory factors. Conclusion Dysregulation of miR-29c-3p and Fer plays a role in RF. Pharmaceutical or genetic inhibition of Fer may serve as the potential treatment for RF.

Aims:: To investigate the role of autophagy in the tight junction of human brain endothelial cells during hypoxia and ischemia. Background:: Endothelial cells play an important role in the initiation, progression and recovery from ischemic stroke. The role of autophagy on human brain endothelial cells (HBECs) subjected to oxygen-glucose deprivation (OGD) is not fully elucidated. Objective:: The objective of this study was to investigate the effect of autophagy on HBECs during OGD. Methods:: HBECs were cultured in a 96-well plate and underwent 4 hours of OGD. For drug treatment, 3-Methyladenine (3-MA) (5mmol/L), an inhibitor of autophagy, was added at the start of OGD. Cell viability and cytotoxicity were tested by cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays. Morphological changes in cells were examined by immunofluorescence microscopy. The protein expression of light chain 3 (LC3) was measured. Autophagosomes and endothelial cell tight junctions were observed using transmission electron microscopy. Results:: The results showed that OGD induced serious damage to HBECs. Cell viability was decreased significantly and LDH release increased significantly (p<0.05) following OGD. 3-MA protected HBECs from damage. Immunostaining further confirmed these results. Since 3-MA is an inhibitor of autophagy, we chose to examine alterations in the amount of LC3, a marker of autophagy. The ratios of LC3-II to LC3-I were significantly lower in the 3-MA treated OGD group than in the non-3-MA treated OGD group (p<0.05). Electron microscopy showed that 3-MA inhibited the formation of autophagolysosomes and revealed that the tight junction ultrastructure of HBECs, which was destroyed by OGD, was significantly protected by treatment with 3-MA. Conclusions:: Autophagy is a key response to oxygen-glucose deprivation stress and its detrimental effects are closely related to the destruction of tight junctions of human brain endothelial cells. Strategies to inhibit autophagy could help to preserve tight junctions.

Objectives To observe the association between passive leg raising (PLR) and the cross-sectional area (CSA) of the right internal jugular vein (IJV) in obese patients undergoing elective surgery. Design Prospective observational study with randomised position sequence. Setting Single-centre, tertiary care hospital in Shanghai, China. Participants Forty obese patients (body mass index (BMI) >30 kg/m²) scheduled for elective surgery were enrolled. Inclusion criteria were American Society of Anesthesiologists Physical Status Classification (ASA) physical status II–III and age ≥18 years. Exclusion criteria included history of neck surgery, severe cardiovascular disease, end-stage renal disease, severe infection or sepsis and significant coagulopathy. Observations Patients underwent ultrasound measurements of the right IJV in two positions: supine (S0) and passive leg raise at 40° (PLR40). Each position was maintained for at least 1 min prior to measurement. Primary outcome The primary outcome was to observe whether the CSA of the right IJV differed between the S0 position and passive leg elevation. In post hoc analyses, we examined factors affecting the relative CSA change (CSAγ), including neck circumference, BMI, age, sex, ASA physical status and heart rate as predictors. Results The CSA of the right IJV was significantly larger in the PLR40 position (2.05 cm²) compared to the S0 position (1.67 cm², p=0.003). Linear regression analysis showed a slight positive correlation between neck circumference and the percentage change in CSA (correlation coefficient: 0.066, p<0.05). Conclusion The CSA of the right IJV was significantly larger in the PLR40 position in obese patients undergoing surgery. Trial registration number Chinese Clinical Trial Registry ChiCTR2400080513.