Background: Gliomas are the most common primary malignant brain tumors and have a poor prognosis. Early detection of gliomas is crucial to improve patient outcomes. Urine accumulates systematic body changes and thus serves as an excellent early biomarker source. Methods: At the biomarker discovery phase, we performed a self-controlled proteomics analysis by comparing urine samples collected from five glioma patients at the time of tumor diagnosis and after surgical removal of the tumor. At the biomarker validation phase, we further validated some promising proteins using parallel reaction monitoring (PRM)-based targeted proteomics in another cohort, including glioma, meningioma, and moyamoya disease patients as well as healthy controls. Results: Using label-free proteome quantitation (LFQ), we identified twenty-seven urinary proteins that were significantly changed after tumor resection, many of which have been previously associated with gliomas. The functions of these proteins were significantly enriched in the autophagy and angiogenesis, which are associated with glioma development. After targeted proteomics validation, we identified a biomarker panel (AACT, TSP4, MDHM, CALR, LEG1, and AHSG) with an area under the curve (AUC) value of 0.958 for the detection of gliomas. Interestingly, AACT, LEG1, and AHSG are also potential cerebrospinal fluid or blood biomarkers of gliomas. Conclusions: Using LFQ and PRM proteome quantification, we identified candidate urinary protein biomarkers with the potential to detect gliomas. This study will also provide clues for future biomarker studies involving brain diseases.

The immune system of skin develops in stages in mice. However, the developmental dynamics of immune cells in human skin remains elusive. Here, we perform transcriptome profiling of CD45⁺ hematopoietic cells in human fetal skin at an estimated gestational age of 10-17 weeks by single-cell RNA sequencing. A total of 13 immune cell types are identified. Skin macrophages show dynamic heterogeneity over the course of skin development. A major shift in lymphoid cell developmental states occurs from the first to the second trimester that implies an in situ differentiation process. Gene expression analysis reveals a typical developmental program in immune cells in accordance with their functional maturation, possibly involving metabolic reprogramming. Finally, we identify transcription factors (TFs) that potentially regulate cellular transitions by comparing TFs and TF target gene networks. These findings provide detailed insight into how the immune system of the human skin is established during development.

Objectives: This study aimed to investigate the effectiveness of transcutaneous auricular vagal nerve stimulation (taVNS) in alleviating postoperative pain following thoracoscopic lobectomy. Methods: In this randomized controlled trial, 70 adult patients were randomly assigned in a 1:1 ratio to receive either active or sham taVNS. Stimulation was initiated in the preoperative room, maintained throughout surgery, and discontinued after extubation in the post-anesthesia care unit, at which point the device was removed. Additional 2-hour sessions were conducted each morning on postoperative days 1 and 2. Patient-controlled intravenous analgesia and serratus anterior plane block were provided to all the patients. The primary outcome was sufentanil consumption during the first 24 hours after surgery. Results: A total of 67 participants completed the study. Sufentanil consumption showed no statistically significant difference between the active group (33 ± 13 μg) and the sham group (32 ± 9 μg) (mean difference=1.20, 95% confidence interval=−4.23 to 6.63, P-value=0.661). Compared to the sham group, taVNS produced a statistically significant reduction in the numerical rating scale for resting pain (P-value=0.001) and deep breathing pain (P-value<0.001) postoperatively. taVNS also significantly reduced the incidence of rebound pain (58% vs. 18%; P-value=0.001) and chronic postsurgical pain at three months (27% vs. 6%; P-value=0.018). Discussion: taVNS did not reduce postoperative opioid consumption but alleviated acute postoperative pain, lowered the incidence of rebound pain and chronic postsurgical pain. These preliminary findings have uncertain clinical significance and require further investigation. Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2400081062).

Neuropathic pain (NP) is a debilitating condition driven by chronic neuroinflammation, where abnormal communication between microglia and astrocytes amplifies pain signaling. Current therapies offer limited benefit and primarily address symptoms rather than underlying mechanisms. Here, we show that transferrin- and phosphatidylserine-modified liposomes carrying a TDP-43 aggregation inhibitor (TF/PS/TDP-43-IN-1) effectively cross the blood–brain barrier, target glial cells, and modulate their activation states. In vitro, the formulation improved cell viability and promoted anti-inflammatory phenotypes. In vivo, studies conducted in male C57BL/6 J mice demonstrated significant alleviation of pain behaviors, reduced inflammatory cytokine expression, and suppression of the cGAS–STING pathway. These findings indicate that targeting TDP-43 aggregation with a nanocarrier system can reprogram glial interactions to relieve neuropathic pain. This strategy highlights a promising approach for developing targeted, disease-modifying therapies that act on key drivers of neuroinflammation.

Introduction Postoperative delirium (POD) is a frequent complication in elderly patients undergoing major surgery. Research has shown that neuroinflammation, postoperative pain and autonomic nervous system dysfunction play significant roles in its onset. Vagus nerve stimulation (VNS) has the potential to reduce inflammation, ease postoperative pain and aid in recovery by enhancing acetylcholine release and activating the cholinergic anti-inflammatory pathway. This study aims to assess the effectiveness and safety of transauricular VNS (ta-VNS) in preventing POD in elderly patients undergoing major surgery. Methods and analysis This multicentre, participant-blinded and assessor-blinded, randomised, parallel-group controlled trial will compare the incidence of POD in elderly patients undergoing major surgery who receive ta-VNS versus sham stimulation. A total of 300 eligible patients will be randomly assigned in a 1:1 ratio to either the active or sham stimulation group. The active stimulation group will receive electrical stimulation to the left cymba conchae at a frequency of 30 Hz and a pulse width of 250 µs, with a 30 s on/30 s off cycle. The intensity will start at 0.4V and be increased in 0.4V increments until a tingling sensation is felt, then adjusted to the highest tolerable level without pain. After obtaining informed consent and randomisation, the initial intervention will begin in the preoperative area and continue throughout the surgery. For the four postoperative days, the intervention will be administered twice daily in 2-hour sessions each morning and afternoon. The sham group will follow the same procedure, with electrodes placed on the left cymba conchae. After adjusting the stimulation intensity, the device will be switched off. The primary outcome is the incidence of POD from postoperative day 0 to day 7 or discharge. Secondary outcomes include the severity of POD, quality of recovery, sleep quality and adverse events. Ethics and dissemination The protocol was approved by Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine on 9 January 2024 (Approval number: 20240014), and the trial was registered on the Chinese Clinical Trial Registry on 21 February 2024, prior to recruitment. The study will be performed according to the guidelines of the Declaration of Helsinki. Written informed consent will be obtained from all participants. The results will be submitted for publication in a refereed journal. Trial registration number ChiCTR2400081078.

Background: Postoperative atrial fibrillation (POAF) is a common complication after esophagectomy and is associated with adverse outcomes. This study investigated whether preoperative stellate ganglion block (SGB) could reduce the incidence of POAF and improve postoperative recovery. Methods: In this single-center, randomized, double-blind, placebo-controlled trial, 100 patients undergoing esophagectomy were randomly assigned to receive ultrasound-guided right-sided SGB with 7 mL of either 0.5% ropivacaine (SGB group) or normal saline (control group). The primary outcome was the incidence of POAF within 72 hours postoperatively. Secondary outcomes included the timing and duration of POAF, heart rate variability, other arrhythmias, sufentanil consumption, pain scores, vital signs, sleep quality, gastrointestinal recovery, length of hospital stay, complications and mortality. Results: The incidence of POAF was 10% in both groups (OR = 1.0, 95% CI: 0.27– 3.69, p > 0.99). However, patients in the SGB group experienced significantly fewer premature atrial contractions (97 vs 347; p = 0.038), lower pain scores (VAS at rest: B = – 0.60, p < 0.001; during movement: B = – 0.67, p < 0.001) and lower heart rate on postoperative day 1 (B = – 4.29, p = 0.026). Regarding gastrointestinal recovery, the SGB group showed significantly shorter times to first flatus (p = 0.001) and first semi-liquid intake (p = 0.027). Sleep disturbances were also less frequent in the SGB group (4% vs 21%, OR = 0.08, p = 0.039). No significant differences were observed between the groups in terms of length of hospital stay, incidence of postoperative complications or mortality. Conclusion: Although SGB did not reduce the incidence of POAF, it was associated with improved postoperative recovery. These findings suggest that SGB may serve as a beneficial adjunct to optimize recovery following esophagectomy.