ObjectiveTo investigate the effect of quercetin on acute gouty arthritis （GA） in rats by inhibiting the reactive oxygen species （ROS）/NOD-like receptor protein 3 （NLRP3）/interleukin-1β （IL-1β） signaling pathway. MethodsSixty SPF-grade male SD rats were randomized into normal， model， colchicine （0.3 mg·kg^-1）， and low-， medium-， and high-dose （25， 50， 100 mg·kg^-1， respectively） quercetin groups （n=10）. The rats in the dosing groups were administrated with the corresponding drugs （10 mL·kg^-1） by gavage once a day for one week. An equal volume of normal saline was given by gavage to rats in normal and model groups. One hour after drug administration on day 5， an acute GA model was established in other groups except the control group via intra-articular injection of monosodium urate （MSU） suspension into the right posterior ankle joint cavity. The joint swelling and gait were scored at the time points of 6， 12， 24， 48 h after modeling. Histopathological alterations in the ankle joint tissue from each group were assessed by hematoxylin-eosin （HE） staining. Malondialdehyde （MDA）， xanthine oxidase （XOD）， and total superoxide dismutase （T-SOD） assay kits were used to assess the levels of MDA， XOD， and T-SOD in the serum. The levels of tumor interleukin-6 （IL-6）， necrosis factor-α （TNF-α）， and IL-1β in the rat serum， as well as ROS in the ankle joint tissue， were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was performed to determine the protein levels of NLRP3， thioredoxin-interacting protein （TXNIP）， apoptosis-associated speck-like protein containing a CARD domain （ASC）， precursor cysteinyl aspartate-specific proteinase-1 （pro-Caspase-1）， cleaved Caspase-1 （Caspase-1 p20）， and IL-1β in the ankle joint tissue. Real-time PCR was employed to assess the mRNA levels of TXNIP， NLRP3， ASC， IL-1β， and TNF-α in the ankle joint tissue. ResultsCompared with the normal group， the model group exhibited decreased spontaneous activity， mental fatigue， increased ankle joint swelling and gait scores （P<0.01）， aggravated synovial tissue edema and inflammatory cell infiltration （P<0.01）， elevated levels of XOD， MDA， TNF-α， IL-1β， and IL-6 in the serum and ROS in the joint tissue （P<0.01）， a declined level of T-SOD （P<0.01）， up-regulated protein levels of NLRP3， TXNIP， ASC， pro-Caspase-1， Caspase-1 p20， and IL-1β in the ankle joint tissue （P<0.01）， and up-regulated mRNA levels of NLRP3， TXNIP， ASC， IL-1β， and TNF-α in the ankle joint tissue （P<0.01）. Compared with the model group， the medium- and high-dose quercetin groups showed improved general conditions， decreased gait scores （P<0.05， P<0.01）， reduced joint swelling （P<0.01）， alleviated synovial tissue edema and inflammatory cell infiltration （P<0.05， P<0.01）， lowered levels of XOD， MDA， TNF-α， IL-1β， and IL-6 in the serum and ROS in the joint tissue （P<0.01）， increased levels of T-SOD （P<0.01）， down-regulated protein levels of TXNIP， NLRP3， ASC， pro-Caspase-1， Caspase-1 p20， and IL-1β in the ankle joint tissue （P<0.05， P<0.01）， and down-regulated mRNA levels of TXNIP， NLRP3， ASC， IL-1β， and TNF-α in the ankle joint tissue （P<0.01）. Low-dose quercetin also ameliorated some of the above parameters （P<0.05， P<0.01）. ConclusionQuercetin exerts anti-GA effects by blocking the ROS/NLRP3/IL-1β signaling pathway， downregulating NLRP3 inflammasome activation， and inhibiting the production of pro-inflammatory cytokines including TNF-α， IL-1β， and IL-6.

Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

ObjectiveTo explore the effect of respiratory neuromuscular biphasic synchronous stimulation on weaning from ventilator dependence in patients with severe neurological disorders undergoing tracheotomy. MethodsFrom May, 2023 to March, 2025, 94 critically ill patients with nerve related tracheostomy and ventilator dependence admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University were randomly divided into control group (n = 47) and observation group (n = 47). The control group received conventional treatment and comprehensive rehabilitation, while the observation group received respiratory nerve and muscle biphasic synchronous stimulation therapy on this basis. The oxygenation index (PaO₂/FiO₂), diaphragm mobility, diaphragm thickening rate, maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), mechanical ventilation time and weaning success rate were compared before, and two and four weeks after treatment. ResultsThree cases in the control group and one in the observation group were dropped out. There was no significant difference in various indicators between two groups before treatment (P > 0.05). Two and four weeks after treatment, PaO₂/FiO₂, diaphragm movement, diaphragm thickening rate, MIP and MEP improved with the prolongation of time in both groups (F > 23.632,P < 0.001), and they were better in the observation group than in the control group (P < 0.05). The mechanical ventilation time was shorter (t = 2.287, P < 0.05) and the success rate of weaning was higher (χ² = 4.622, P < 0.05) in the observation group than in the control group. ConclusionThe respiratory neuromuscular biphasic synchronous stimulation can be applied to patients with severe neurological conditions who are dependent on tracheotomy ventilators, to accelerate the recovery of respiratory muscle strength, shorten the duration of mechanical ventilation, and increase the success rate of weaning from the ventilator.

Objective:To investigate the correlation between triglyceride-glucose-body mass index (TyG-BMI index) and the outcome of young patients with acute ischemic stroke (AIS).Methods:Consecutive young patients with first-ever AIS (aged 18-45 years) admitted to Pingyi County People's Hospital and Qingdao Municipal Hospital from January 2020 to December 2023 were included retrospectively. The demographic data, vascular risk factors, baseline blood pressure, baseline laboratory tests, classification of stroke etiology, baseline National Institutes of Health Stroke Scale (NIHSS) scores, and main treatment methods were collected. At 3 months after the onset of stroke, the modified Rankin Scale was used for outcome evaluation. A score of 0-2 was defined as good outcome and >2 were defined as poor outcome. Multivariate logistic regression analysis was used to identify independent factors associated with poor outcome in young patients with AIS. Results:A total of 253 young patients with AIS were enrolled, including 196 males (77.5%), aged 38.65±5.34 years; baseline NIHSS score 3.03±2.88. At 90 days after onset, 206 patients (81.4%) had good outcome, while 47 (18.6%) had poor outcome. The poor outcome group had significantly higher systolic blood pressure, triglycerides, fasting blood glucose, triglyceride glucose (TyG) index, body mass index (BMI), TyG-BMI index, and baseline NIHSS score than those of the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for gender, systolic blood pressure, baseline NIHSS score, and antiplatelet drug use, the TyG-BMI index was significantly independently associated with the poor outcome in young patients with AIS (odds ratio 1.039, 95% confidence interval 1.021-1.057; P<0.001). Conclusion:A higher baseline TyG-BMI index is independently associated with the poor outcome in young patients with AIS.

Objective:To evaluate the effect of disulfiram on sepsis-associated encephalopathy (SAE) and the relationship with NOD-like receptor family pyrin domain-containing 3 (NLRP3)/caspase-1 signaling pathway in rats.Methods:Forty-five SPF healthy male Sprague-Dawley rats, aged 8-12 weeks, weighing 200-220 g, were divided into 3 groups ( n=15 each) using a random number table method: sham operation group, SAE group, and SAE+ disulfiram group (SAE+ DSF group). The SAE model was established by by using cecal ligation and puncture in anesthetized rats. SAE+ DSF group received an intraperitoneal injection of 50 mg/kg disulfiram 4 h before the cecal ligation and puncture. The survival status of rats was recorded within 72 h after surgery. Their neurobehavioral scores were assessed and recorded on days 1-3 after surgery. On the 3rd day after surgery, novel object recognition test (cognitive index) and open field test (activity distance and time in the central area) were conducted sequentially. Following the behavioral testing, the rats were anesthetized, and their hippocampi were dissected and isolated to observe the pathological changes in the hippocampal region (using HE staining) and to determine the expression of NLRP3 and caspase-1 (by Western blot) and the expression of interleukin-1beta (IL-1β), IL-18 and tumor necrosis factor-alpha (TNF-α) mRNA (by fluorescent quantitative polymerase chain reaction). Results:Compared with Sham group, the 72-h survival rate and postoperative neurobehavioral scores were significantly decreased, the activity distance and time in the central area of the open field were shortened, and the cognitive index was decreased, the expression of NLRP3, caspase-1 and IL-1β, IL-18 and TNF-α mRNA was up-regulated ( P<0.05), and the pathological damage was marked in the hippocampus in SAE group ( P<0.05). Compared with SAE group, postoperative neurobehavioral scores were significantly increased, the activity distance and time in the central area of the open field were prolonged, the cognitive index was increased, and the expression of NLRP3 and caspase-1 and IL-1β, IL-18 and TNF-α mRNA was down-regulated ( P<0.05), no significant change was found in the 72-h survival rate ( P>0.05), and the pathological damage to the hippocampus was significantly alleviated in SAE+ DSF group. Conclusions:Disulfiram can alleviate SAE in rats, and the mechanism may be related to the inhibition of the NLRP3/caspase-1 signaling pathway.

Emergence agitation(EA)is a common complication after general anesthesia,especially in children and adolescents.Remifentanil,as a short-acting μ-receptor agonist,has become an important drug for the prevention and treatment of EA due to its rapid recovery and low risk of respiratory depression.This article reviews the mechanism of action and clinical research progress of remifentanil in the prevention and treatment of EA.Its mechanism of action involves the inhibition of pain signals mediated by traditional μ-receptor activation and potential new mechanism based on neural-endocrine-immune network,including regulation of microglial inflammatory pathways,and the modulation of cytokines and chemokines,etc.Clinical studies have shown that remifentanil can significantly shorten the recovery time,reduce the incidence of EA,and further optimize the analgesic effect and recovery quality by combining with other drugs(such as local anesthetics,sedatives,and opioid drugs).Future research should further explore the mechanism of action of remifentanil,optimize clinical treatment strategies,and conduct large-scale clinical trials to standardize the drug use plan,while paying attention to its long-term effects and the development of multimodal treatment plans to promote the further development of EA prevention and treatment plans.

Knee osteoarthritis(KOA)is a common musculoskeletal disease,and ferroptosis is a new type of programmed cell death involving iron ions.This paper summarized the relationship between the pathological changes of ferroptosis and the onset of KOA,and reviewed the progress of traditional Chinese medicine(TCM)intervention in KOA based on the pathological changes of ferroptosis.The pathological changes of ferroptosis are mainly related to the imbalance of amino acid antioxidant system,iron metabolism disorder and lipid peroxide accumulation.The cystine/glutamate antiporter(System XC-),glutathione(GSH)and glutathione peroxidase 4(GPX4)are the core targets for regulating ferroptosis,involving the main signaling pathways for studying the TCM intervention of KOA via ferroptosis.Single herbs such as Drynariae Rhizoma,Scutellariae Barbatae Herba,Epimedii Folium,Astragali Radix,Ligustri Lucidi Fructus,and Achyranthis Bidentatae Radix,and multi-herb formulae such as Duhuo Jisheng Decoction and Yougui Pills,can inhibit the ferroptosis of chondrocytes through multiple targets and multiple pathways,thus treating KOA.The research of the TCM intervention on the ferroptosis of chondrocytes and its associated signaling pathways can provides a novel approach for expanding the TCM therapy of KOA.

Objective:To evaluate the effect of disulfiram on sepsis-associated encephalopathy (SAE) and the relationship with NOD-like receptor family pyrin domain-containing 3 (NLRP3)/caspase-1 signaling pathway in rats.Methods:Forty-five SPF healthy male Sprague-Dawley rats, aged 8-12 weeks, weighing 200-220 g, were divided into 3 groups ( n=15 each) using a random number table method: sham operation group, SAE group, and SAE+ disulfiram group (SAE+ DSF group). The SAE model was established by by using cecal ligation and puncture in anesthetized rats. SAE+ DSF group received an intraperitoneal injection of 50 mg/kg disulfiram 4 h before the cecal ligation and puncture. The survival status of rats was recorded within 72 h after surgery. Their neurobehavioral scores were assessed and recorded on days 1-3 after surgery. On the 3rd day after surgery, novel object recognition test (cognitive index) and open field test (activity distance and time in the central area) were conducted sequentially. Following the behavioral testing, the rats were anesthetized, and their hippocampi were dissected and isolated to observe the pathological changes in the hippocampal region (using HE staining) and to determine the expression of NLRP3 and caspase-1 (by Western blot) and the expression of interleukin-1beta (IL-1β), IL-18 and tumor necrosis factor-alpha (TNF-α) mRNA (by fluorescent quantitative polymerase chain reaction). Results:Compared with Sham group, the 72-h survival rate and postoperative neurobehavioral scores were significantly decreased, the activity distance and time in the central area of the open field were shortened, and the cognitive index was decreased, the expression of NLRP3, caspase-1 and IL-1β, IL-18 and TNF-α mRNA was up-regulated ( P<0.05), and the pathological damage was marked in the hippocampus in SAE group ( P<0.05). Compared with SAE group, postoperative neurobehavioral scores were significantly increased, the activity distance and time in the central area of the open field were prolonged, the cognitive index was increased, and the expression of NLRP3 and caspase-1 and IL-1β, IL-18 and TNF-α mRNA was down-regulated ( P<0.05), no significant change was found in the 72-h survival rate ( P>0.05), and the pathological damage to the hippocampus was significantly alleviated in SAE+ DSF group. Conclusions:Disulfiram can alleviate SAE in rats, and the mechanism may be related to the inhibition of the NLRP3/caspase-1 signaling pathway.

Objective·To compare the safety and short-term outcomes of robot-assisted versus laparoscopic-assisted proximal gastrectomy combined with double-flap esophagogastrostomy in the treatment of early upper gastric cancer.Methods·A retrospective cohort study was conducted to analyze the clinical and pathological data of 31 early gastric cancer patients who underwent proximal gastrectomy combined with double-flap esophagogastrostomy for gastrointestinal reconstruction at the Department of Gastrointestinal Surgery,Renji Hospital,Shanghai Jiao Tong University School of Medicine,from September 2023 to March 2024.Based on the surgical approach,patients were divided into the robot-assisted surgery group(robotic group,20 cases)and the laparoscope-assisted surgery group(laparoscopic group,11 cases).General clinical data,intraoperative conditions,and postoperative recovery between the two groups were compared.At the 6-month postoperative follow-up,upper gastrointestinal radiography and esophagogastroscopy were performed to assess anastomotic stricture and gastroesophageal reflux disease.Additionally,the gastric cancer-specific module of the European Organization for Research and Treatment of Cancer(EORTC),Quality of Life Questionnaire-Stomach 22(QLQ-STO22),was used to evaluate the patients' quality of life.Results·The general data of the two groups,including gender,age,preoperative comorbidities,American Society of Anesthesiologists(ASA)classification,Siewert classification,and pathological staging of tumors,showed no statistically significant differences(all P>0.05).All patients successfully underwent the procedure without conversion to open surgery.The time for gastroesophageal anastomosis was significantly shorter in the robotic group compared to the laparoscopic group[(31.09±8.23)min vs(43.73±8.83)min,P<0.001],while there were no statistically significant differences in other intraoperative and postoperative parameters,including operative time,intraoperative blood loss,number of lymph nodes removed,duration of gastric tube placement,time to start a liquid diet,length of postoperative hospital stay,and incidence of postoperative complications(all P>0.05).At the 6-month postoperative follow-up,30 patients completed the follow-up,with one patient lost to follow-up in the robotic group.Upper gastrointestinal radiography and esophagogastroscopy results showed that only one patient in the laparoscopic group developed an anastomotic stricture,while one patient in the robotic group developed grade A and one developed grade B gastroesophageal reflux disease(GERD).In addition,one patient in the laparoscopic group also developed grade B GERD.The incidences of GERD and anastomotic stricture showed no statistically significant differences between the two groups(both P>0.05).EORTC QLQ-STO22 results indicated that the robotic group had significantly lower scores in the dimensions of dysphagia,gastroesophageal reflux,and dietary restrictions,as well as in the total score,compared to the laparoscopic group(all P<0.05).Conclusion·Robot-assisted proximal gastrectomy combined with double-flap esophagogastrostomy is safe and feasible.It shortens anastomosis time and offers potential advantages in postoperative functional recovery and quality of life improvement.

Objective:To develop and validate a 30-day readmission risk prediction model for patients with chronic obstructive pulmonary disease (COPD) using multiple machine learning algorithms.Methods:Convenience sampling was used to select 1 450 COPD patients hospitalized at Tianjin Medical University General Hospital from January 2017 to December 2023 as study subjects. Twenty-nine variables associated with readmission were included. LASSO was used to screen for primary characteristic variables associated with 30-day readmission. The 1 450 patients were divided into a training set ( n=870) and a test set ( n=580) in a 6∶4 ratio. Ten machine learning methods, including random forest, AdaBoost, extreme radient Boosting (XGB), decision tree and so on, were used for model training and testing to identify the optimal prediction model. The optimal model and SHAP were employed to analyze key features and rank characteristic importance. Results:Among 1 450 COPD patients, the 30-day readmission rate was 24.48% (355/1 450). There were no significant differences in the general information between patients in test set and training set ( P>0.05). LASSO regression analysis identified seven variables with the highest predictive value, namely regular weekly exercise, hospital stay, mean arterial pressure, forced expiratory volume in one second/forced vital capacity (FEV1/FVC), C-reactive protein, body mass index, and medication adherence. Machine learning showed that in the training set, XGB had the highest area under the receiver operating characteristic curve ( AUC), sensitivity, and F1 score of 0.943, 0.926, and 0.930, respectively. In the test set, the AUC and accuracy of XGB were 0.882 and 0.858, respectively, and XGB's various scores showed that it had good generalization and predictive performance. XGB analysis showed that medication adherence, FEV1/FVC, and regular weekly exercise were negatively correlated with the 30-day readmission risk, while body mass index, C-reactive protein, mean arterial pressure, and hospital stay were positively correlated. The characteristics ranked in order of importance were medication adherence, body mass index, C-reactive protein, mean arterial pressure, FEV1/FVC, hospital stay and regular weekly exercise. Conclusions:The XGB model has strong predictive performance and good generalization ability, which can effectively predict the 30-day readmission risk of COPD patients, assist in clinical identification of high-risk patients, implement nursing interventions, and reduce readmission rates.