Dong-yu Zheng’s research while affiliated with First Affiliated Hospital of China Medical University and other places

Background Postoperative nausea and vomiting (PONV) is the most common complication following general anesthesia. Currently, pharmaceutical therapy is the primary method of treatment, but it has reached a plateau, and it is accompanied by inherent adverse reactions and high costs. Stimulation of the wrist acupuncture point PC6 is recommended as an effective means of preventing PONV. Our previous study suggests that the wearable transcutaneous electrical acupoint stimulation (TEAS) bracelet can prevent PONV, but its effectiveness in treating moderate-to-severe PONV that has already occurred remains unknown. This trial aims to include female patients who have suffered from PONV after general anesthesia in real-world settings to investigate the therapeutic effect of the TEAS bracelet. Methods This trial will be conducted in Shanghai and Tianjin, China, with a total of 232 participants recruited from four academic hospitals. Participants will be randomly allocated into the TEAS group or the control group in a 1:1 ratio. Participants in the TEAS group will wear an EmeTerm bracelet and be injected with normal saline, while participants in the control group will wear a model bracelet and be injected with 10 mg of metoclopramide. Follow-up will be conducted 2 h later, and participants who do not experience relief will be randomly allocated into two groups and given cross-intervention. The primary outcome of the trial is the response rate of moderate-to-severe PONV after 2 h of intervention. Secondary outcomes include the recurrence rate of moderate-to-severe PONV within 24 h after intervention and the response rate of moderate-to-severe PONV at 2 h after cross-intervention in a population insensitive to the initial intervention. Discussion This multi-center randomized controlled trial aims to reveal the therapeutic effect of the wearable TEAS bracelet on PONV. It is expected that this bracelet will become an effective supplement for the clinical treatment of PONV, reducing medical expenditure and improving anesthesia quality and patient satisfaction. Trial registration Chinese Clinical Trial Registry ChiCTR2400084329. Registered on May 14, 2024.

Background Ventilator-induced lung injury (VILI) is caused by overdistension of the alveoli by the repetitive recruitment and derecruitment of alveolar units. This study aims to investigate the potential role and mechanism of fibroblast growth factor 21 (FGF21), a metabolic regulator secreted by the liver, in VILI development. Methods Serum FGF21 concentrations were determined in patients undergoing mechanical ventilation during general anesthesia and in a mouse VILI model. Lung injury was compared between FGF21-knockout (KO) mice and wild-type (WT) mice. Recombinant FGF21 was administrated in vivo and in vitro to determine its therapeutic effect. Results Serum FGF21 levels in patients and mice with VILI were significantly higher than in those without VILI. Additionally, the increment of serum FGF21 in anesthesia patients was positively correlated with the duration of ventilation. VILI was aggravated in FGF21-KO mice compared with WT mice. Conversely, the administration of FGF21 alleviated VILI in both mouse and cell models. FGF21 reduced Caspase-1 activity, suppressed the mRNA levels of Nlrp3 , Asc, Il-1β, Il-18, Hmgb1 and Nf-κb , and decreased the protein levels of NLRP3, ASC, IL-1β, IL-18, HMGB1 and the cleaved form of GSDMD. Conclusions Our findings reveal that endogenous FGF21 signaling is triggered in response to VILI, which protects against VILI by inhibiting the NLRP3/Caspase-1/GSDMD pyroptosis pathway. These results suggest that boosting endogenous FGF21 or the administration of recombinant FGF21 could be promising therapeutic strategies for the treatment of VILI during anesthesia or critical care.

Background General anaesthesia and interscalene brachial plexus block (ISB) are the main anaesthesia methods for patients undergoing shoulder arthroscopy. However, they usually result in severe complications, such as postoperative nausea and vomiting (PONV), postoperative cognitive dysfunction (POCD), and hemi-diaphragmatic paralysis (HDP). Compared with ISB, superior trunk block (STB) is associated with a lower incidence of HDP and greater hand strength. Previous studies of STB have proven that it could provide surgical anaesthesia and noninferior postoperative analgesia, but the incidence of partial HDP was still very high, which may be fatal for some specific populations, such as patients with preexisting pulmonary impairments. Moreover, a high dose of local anaesthetic (LA) can result in prolonged postoperative numbness and weakness in the affected upper limb. Adverse events can be avoided by reducing the dose of LA, namely by using the minimum effective volume (MEV) or concentration (MEC). In this study, we aimed to explore the MEV of ropivacaine 0.25%, providing satisfactory surgical anaesthesia during the performance of an STB. Methods/design Our study is a prospective cohort trial to determine the minimum effective volume of ropivacaine 0.25% in 90% of patients (MEV90) on the provision of surgical anaesthesia for shoulder arthroscopy. Trial designs apply the up-and-down Biased Coin Design (BCD) methodology, which has been adopted in recent years in dose-finding studies for regional anaesthesia. Participants will be enrolled and receive STB with different volumes of ropivacaine 0.25%. The volume of ropivacaine administered to each patient depends on the outcome of the previous one. A volume of 5 ml is chosen for the initial case on the basis of prior clinical experience. In case of failure, the next patient will receive a higher volume (defined as the previous volume with an increment of 2 ml). The successful block will be defined as not only achieving a minimal score of 9 points (out of 10 points) after 30 minutes of STB using a sensory composite scale but also completing the surgery with only STB without general anaesthesia. The volume of LA for the subsequent case is then randomized according to the BCD principle. Discussion This research will determine the MEV90 of ropivacaine 0.25% of STB in patients undergoing shoulder arthroscopy. The results of the study will be important for guiding clinical practice and making it possible to enhance recovery after surgery for patients in day wards undergoing shoulder arthroscopic surgery.

Prostaglandin E receptor subtype 4 (EP4) is widely distributed in the heart, but its role in hepatic ischemia/reperfusion (I/R), particularly in mitochondrial permeability transition pore (MPTP) modulation, is yet to be elucidated. In the present study, an EP4 agonist (CAY10598) was used in a rat model to evaluate the effects of EP4 activation on liver I/R and the mechanisms underlying this. I/R insult upregulated hepatic EP4 expression during early reperfusion. In addition, subcutaneous CAY10598 injection prior to the onset of reperfusion significantly increased hepatocyte cAMP concentrations and decreased serum ALT and AST levels and necrotic and apoptotic cell percentages, after 6 h of reperfusion. Moreover, CAY10598 protected mitochondrial morphology, markedly inhibited mitochondrial permeability transition pore (MPTP) opening and decreased liver reactive oxygen species levels. This occurred via activation of the ERK1/2‑GSK3β pathway rather than the janus kinase (JAK)2‑signal transducers and activators of transcription (STAT)3 pathway, and resulted in prevention of mitochondria‑associated cell injury. The MPTP opener carboxyatractyloside (CATR) and the ERK1/2 inhibitor PD98059 also partially reversed the protective effects of CAY10598 on the liver and mitochondria. The current findings indicate that EP4 activation induces ERK1/2‑GSK3β signaling and subsequent MPTP inhibition to provide hepatoprotection, and these observations are informative for developing new molecular targets and preventative therapies for I/R in a clinical setting.