(1) Background: Previous evidence demonstrates that tight glycemic control and good physical function could reduce the risk of delirium. This study aimed to investigate whether the occurrence of postoperative delirium (POD) in older hip fracture surgery patients is associated with preoperative glycemic control factors or pre-injury physical performance. (2) Methods: Three-hundred and nine individuals aged over 65 years and scheduled for hip fracture surgery were included at a single center. Glycemic control factors and pre-injury physical performance were assessed preoperatively. The presence of delirium was assessed using the Confusion Assessment Method on postoperative hospitalization days. Univariate and multivariable logistic regression models and a risk prediction model of POD were established. (3) Results: Among the 309 patients, 52 (16.83%) experienced POD during the hospital stay. The numbers of pre-injury physical performance and type 2 diabetes mellitus (T2DM) patients were significantly different in the POD and non-POD groups. The multivariable model showed that development of delirium was significantly explained by preoperative fasting blood glucose (FBG) (OR 0.804, p = 0.004), stair climbing (OR 0.709, p = 0.003), T2DM (odds ratio (OR) 3.654, p = 0.001), and age-adjusted Charlson comorbidity index (ACCI) (OR 1.270, p = 0.038). The area under the receiver operating characteristic curve (AUROC) of the risk prediction model including those covariates was 0.770. (4) Conclusions: More older T2DM patients develop POD after hip fracture surgery than patients without T2DM. A simple assessment of preoperative FBG and pre-injury stair climbing capacity may identify those at high risk for the development of POD. Higher preoperative FBG and good pre-injury stair climbing capacity are protective factors for POD.

Delayed neurocognitive recovery (dNCR) is a major complication after anesthesia and surgery in older adults. Alpha‐synuclein (α‐syn; encoded by the gene, SNCA) has recently been shown to play an important role in hippocampus‐dependent working memory. Aggregated forms of α‐syn are associated with multiple neurotoxic mechanisms, such as mitochondrial dysfunction and cell death. In this study, we found that blocking α‐syn improved both mitochondrial function and mitochondria‐dependent neuronal apoptosis in a mouse model of dNCR. Various forms of α‐syn (including total α‐syn, phosphorylated‐Ser129‐α‐syn, and oligomers) were upregulated in hippocampal tissue and extracted mitochondria after surgical challenge. Clenbuterol is a novel transcription modulator of Scna. Clenbuterol significantly attenuated surgery‐induced progressive accumulation of various toxic α‐syn forms in the hippocampus, as well as mitochondrial damage and memory deficits in aged mice following surgery. We also observed excessive mitochondrial α‐syn accumulation and increased mitochondria‐mediated apoptosis in vitro using nerve growth factor‐differentiated PC12 cells and primary hippocampal neurons exposed to lipopolysaccharide. To further validate the neuroprotective effect of α‐syn inhibition, we used a lentiviral Snca‐shRNA (Lv‐shSnca) to knockdown Snca. Of note, Lv‐shSnca transfection significantly inhibited neuronal apoptosis mediated by the mitochondrial apoptosis pathway in neurons exposed to lipopolysaccharide. This α‐syn inhibition improved the disruption to mitochondrial morphology and function, as well as decreased levels of apoptosis. Our results suggest that targeting pathological α‐syn may achieve neuroprotection through regulation of mitochondrial homeostasis and suppression of apoptosis in the aged hippocampus, further strengthening the therapeutic potential of targeting α‐syn for dNCR.

The zinc finger E-box-binding transcription factor Zeb1 plays a pivotal role in the epithelial-mesenchymal transition. Numerous studies have focused on the molecular mechanisms by which Zeb1 contributes to this process. However, the functions of Zeb1 beyond the epithelial-mesenchymal transition remain largely elusive. Using a transdifferentiation system to convert mouse embryonic fibroblasts (MEFs) into functional neurons via the neuronal transcription factors achaete-scute family bHLH (basic helix-loop-helix) transcription factor1 (Ascl1), POU class 3 homeobox 2 (POU3F2/Brn2), and neurogenin 2 (Neurog2, Ngn2) (ABN), we found that Zeb1 was up-regulated during the early stages of transdifferentiation. Knocking down Zeb1 dramatically attenuated the transdifferentiation efficiency, whereas Zeb1 overexpression obviously increased the efficiency of transdifferentiation from MEFs to neurons. Interestingly, Zeb1 improved the transdifferentiation efficiency induced by even a single transcription factor (e.g. Asc1 or Ngn2). Zeb1 also rapidly promoted the maturation of induced neuron cells to functional neurons and improved the formation of neuronal patterns and electrophysiological characteristics. Induced neuron cells could form functional synapse in vivo after transplantation. Genome-wide RNA arrays showed that Zeb1 overexpression up-regulated the expression of neuron-specific genes and down-regulated the expression of epithelial-specific genes during conversion. Taken together, our results reveal a new role for Zeb1 in the transdifferentiation of MEFs into neurons.

Postoperative neurocognitive impairment is an urgent problem with global aging accelerating. The prevention and treatment of postoperative neurocognitive impairment have been widely investigated but lack effective strategies. Low-intensity pulsed ultrasound (LIPUS), a non-invasive tool, has shown an effect on neuroprotection, but whether it could attenuate the postoperative neurocognitive impairment and the underlying mechanisms remains unknown. An experimental setup for LIPUS stimulation of the hippocampus was well established. A laparotomy model in aged mice was applied, and a Morris water maze was used to assess cognitive function. RT-qPCR and western blotting were used to detect levels of Piezo1, synapse-associated proteins in the hippocampus, respectively. Immunofluorescent staining was also used to determine the neural activation and Piezo1 expression. The results showed that LIPUS increased synapse-related proteins of the hippocampus and attenuated cognitive impairment in aged mice. Meanwhile, LIPUS suppressed the overexpression of Piezo1 in the hippocampus. We further found that LIPUS promoted Calpain1 activity and increased extracellular regulated protein kinases (Erk) phosphorylation. Our results suggested that LIPUS could improve cognitive impairment and increase hippocampal synaptogenesis through the Piezo1-mediated Calpain1/ Erk pathway. LIPUS could be used as an effective physical intervention to alleviate postoperative cognitive dysfunction in the aged population.

Background: Emergence agitation (EA) is a conscious disturbance after general anesthesia in adult patients that can lead to severe respiratory or circulatory complications and serious physical injury to patients and caregivers. However, the pathophysiological mechanisms underlying EA remain unclear. The present study aimed to identify serum metabolites with significant alterations in EA patients after general anesthesia and enable inferences on their associations with EA.Methods: EA patients were identified by Richmond Agitation-Sedation Scale (RASS) ≥ + 2 among a cohort of adult patients who received elective surgery under general anesthesia in Peking University Third Hospital between 01 June 2020 and 30 December 2020. We further selected sex-, age-, and surgery type-matched non-EA control patients at a 1:1.5 ratio. Postoperative serum samples were collected from both groups of patients. An untargeted metabolic method was used to identify differences in serum metabolomic profiles between the EA patients and the non-EA patients.Results: A total of 19 EA patients and 32 matched non-EA patients were included in the study. After screening and mapping with a database, 12 metabolites showed significant postoperative alterations in EA patients compared with non-EA patients, and were mainly involved in lipid, fatty acid and amino acid metabolism pathways. Receiver operating characteristic curve analyses indicated that vanillic acid, candoxatril, tiglylglycine, 5-methoxysalicylic acid, decanoylcarnitine, and 24-epibrassinolide may be involved in EA pathogenesis after general anesthesia.Conclusion: In this study, we found differences in the serum levels of vanillic acid, candoxatril, tiglylglycine, 5-methoxysalicylic acid, decanoylcarnitine, and 24-epibrassinolide involved in fatty acid metabolism, lipid metabolism, and amino acid metabolism pathways in EA patients compared with non-EA patients, which may demonstrate an EA pathogenesis-associated molecular pattern and contribute toward better understanding of EA occurrence.

Missed abortion is a common occurrence for otherwise healthy women. Immunological factor is one of the most important reasons. Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) is a novel negative immune regulator related to several human diseases. However, the expression level and clinical significance of TIPE2 in missed abortion remain unclear. The expression of TIPE2 mRNA and protein in decidua and chorion from 36 missed abortion patients and 36 healthy controls was detected using quantitative real-time PCR, western blot and immunohistochemistry. In addition, serum TNF-ɑ and IL-10 levels were measured using flow cytometry. Serum estradiol and progesterone levels were measured by radioimmunoassay test. The correlations of TIPE2 protein levels with TNF-ɑ, IL-10, estradiol and progesterone were further analyzed. TIPE2 protein levels were significantly lower in decidual tissues of missed abortion patients than those in healthy controls. The patients with missed abortion had significantly higher levels of serum TNF-ɑ, and lower levels of serum IL-10, estradiol and progesterone compared with healthy controls. The TIPE2 protein levels were positively related to serum IL-10 levels. Our data indicate TIPE2 could play important roles in maintaining the maternal-fetal tolerance and decreased TIPE2 expression in the decidua may be related to the development of missed abortion.