The transition of cancer cells from epithelial state to mesenchymal state awarded hepatocellular carcinoma (HCC) stem cell properties and induced tumorigenicity, drug resistance, and high recurrence rate. Reversing the mesenchymal state to epithelial state by inducing mesenchymal-epithelial remodeling could inhibit the progression of HCC. Using high-throughput screening, chrysin was selected from natural products to reverse epithelial-mesenchymal transition (EMT) by selectively increasing CDH1 expression. The target identification suggested chrysin exerted its anti-HCC effect through covalently and specifically binding threonine 205 (Thr205) of alpha-enolase (ENO1). For the first time, we revealed that ENO1 bound β-catenin mRNA, and recruited YTHDF2 to identify the m6A modified β-catenin in the 3'-UTR region to degrade β-catenin mRNA. Eventually, the CDH1 gene expression was improved through the regulation of β-catenin mRNA. ENO1/β-catenin mRNA interaction might be a promising target for cellular plasticity reprogramming. Moreover, chrysin could mediate mesenchymal‒epithelial remodeling through increasing degradation of β-catenin mRNA by promoting the binding of ENO1 and β-catenin mRNA. To the best of our knowledge, chrysin is the first reported small molecule inducing β-catenin mRNA degradation through binding to ENO1. The water-soluble derivative of chrysin may be a natural product-derived lead compound for circumventing metastasis, recurrence, and drug resistance of HCC by mediating mesenchymal‒epithelial remodeling.

Objective:To compare the diagnostic, staging, and prognostic performance of three AKI criteria (KDIGO, cROCK, and APKD) in patients with pre-existing kidney dysfunction (PKD).Methods:Clinical data from 570 PKD patients admitted to the ICU of the First Affiliated Hospital of Wenzhou Medical University (October 2020-October 2022) were analyzed. Patients were classified by three AKI diagnostic criteria. We compared AKI detection rates and mortality predictions using ROC analysis and logistic regression (reporting ORs with 95% CIs). Results:AKI detection rates differed significantly: APKD 80.7% (460/570), KDIGO 66.0% (376/570), and cROCK 47.0% (268/570) (both P<0.001 vs. APKD). Mortality rates were comparable across criteria (APKD 32.4%, KDIGO 33.0%, cROCK 33.6%; P>0.85). APKD showed superior predictive value for in-hospital mortality (AUC=0.736, 95% CI 0.691-0.781), with significantly higher sensitivity than KDIGO (0.738 vs. 0.663, P<0.001) and cROCK (0.738 vs. 0.613, P<0.001). KDIGO staging identified few AKI2 cases (1.1%), with mortality rates of 27.3% (AKI1), 0% (AKI2), and 37.0% (AKI3). APKD staging demonstrated graded mortality risks: 20.1% (AKI1), 28.1% (AKI2), and 40.9% (AKI3) (all P<0.05). Multivariate analysis revealed increasing mortality risk with APKD stage (AKI1: OR=2.34, 95% CI 1.09-5.31; AKI2: OR=4.50, 95% CI 2.05-10.46; AKI3: OR=7.03, 95% CI 3.59-15.01). APKD staging outperformed KDIGO in mortality prediction (AUC=0.756 vs. 0.724, P=0.02). Conclusions:The APKD criteria demonstrate superior AKI detection in PKD patients and better prognostic prediction compared to KDIGO and cROCK. APKD staging provides more clinically meaningful risk stratification than KDIGO for this population.

Objective:To analyze the clinical characteristics and neurophysiological features of patients with neuralgic amyotrophy (NA) and explore their neurological function status.Methods:Clinical data and neurophysiological findings of 90 patients diagnosed with NA at Beijing Tsinghua Changgung Hospital from September 2016 to January 2024 were collected and their clinical phenotypes and neurophysiological characteristics were systematically summarized and analyzed.Results:Among the 90 patients, males accounted for 60.0% (54 cases) and females accounted for 40.0% (36 cases). The duration of the disease was 12 (3, 36) months (ranged from 1 week to 5 years). The onset age of the patients was 58 (30, 70) (21-87) years. Unilateral involvement was noted in 94.4% (85/90) of patients, exhibiting a left-to-right ratio of 1∶1.3, while only 5.6% (5/90) had bilateral involvement. The majority of patients demonstrated a monophasic clinical course with a recurrence rate of just 2.2% (2/90). The primary clinical manifestations included upper limb pain in 70.0% (63/90) of patients, which progressed to muscle weakness and atrophy within 1 day to 1 month, whereas 30.0% (27/90) of patients without significant pain symptoms. Lesions predominantly affected the upper trunk of the brachial plexus, which accounted for 64.4% (58/90) of patients. Distal nerve injuries in the upper limb were observed in 14.4% (13/90) of patients, with 6.7% (6/90) demonstrating isolated anterior interosseous nerve involvement and another 6.7% (6/90) exhibiting isolated posterior interosseous nerve involvement; 1 case had concurrent anterior and posterior interosseous nerve damage. Additionally, 1 case presented with bilateral phrenic nerve involvement, and another patient had isolated posterior tibial nerve injury. Electrophysiological evaluations of patients with NA revealed that axonal damage to motor nerve fibers was a hallmark feature of the condition. Among patients undergoing motor nerve conduction studies, 68.8% (55/80) exhibited decreased compound muscle action potential amplitude, and 31.3% (25/80) had prolonged latency. Sensory nerve conduction was normal in 60.0% (48/80) of patients, while abnormalities included prolonged latency in 15.0% (12/80), reduced amplitude in 12.5% (10/80), slowed conduction velocity in 8.8% (7/80), and absent waveforms in 3.8% (3/80) of patients. The rates of abnormal nerve conduction findings in motor nerves were the highest in the suprascapular nerve (70.6%, 36/51), followed by the axillary nerve (58.3%, 35/60), musculocutaneous nerve (50.7%, 35/69), long thoracic nerve (6/17), and both anterior and posterior interosseous nerves (7.5%, 6/80 each). In sensory nerves, abnormalities were predominantly noted in the lateral antebrachial cutaneous nerve (30.0%, 12/40). Needle electromyography demonstrated neurogenic damage, most frequently affecting the infraspinatus muscle (69.2%, 18/26), biceps brachii (68.1%, 49/72), and deltoid muscle (65.3%, 47/72). The positive rate of magnetic resonance neurography (MRN) for NA was 62.1% (41/66), among which 63.4% (26/41) showed localized swelling of the brachial plexus, 51.2% (21/41) exhibited T 2 hyperintensity, and 4.9% (2/41) demonstrated denervated changes in the muscles. The positive rate of ultrasound for NA was 71.1% (59/83), with 91.5% (54/59) showing nerve swelling and 8.5% (5/59) exhibiting hourglass constriction .Conclusions:NA is a peripheral neuropathy characterized by spontaneous pain, limb weakness, and (or) muscle atrophy primarily. Its clinical phenotype predominantly involves damage to the upper trunk of the brachial plexus, which can also manifest as isolated mononeuropathy. Neurophysiological findings most commonly reveal the neurogenic damage to the muscles innervated by the upper trunk of the brachial plexus, mainly characterized by the axonal damage to the motor nerves, and pure motor nerve damage may also be observed. MRN and neuroultrasound can assist in qualitative diagnosis.

Objective:To summarize the clinical features of out-of-hospital extracorporeal cardiopulmonary resuscitation(ECPR) patients and analyze the factors associated with discharge survival.Methods:The data of 54 patients with ECPR in the Emergency Center of the Second Hospital Affiliated to Zhejiang University School of Medicine from January 2020 to December 2023 were analyzed. Patients were divided into the survival group and death group based on their survival status within 30 days of discharge. Kaplan Meier method was used to draw the survival curve, and COX regression analysis was used to analyze the relevant factors of survival.Results:(1) A total of 54 patients with ECPR were included in this study. 17 (31.5%) cases were discharged alive, of which 10 (58.8%) had a good neurological prognosis, while 37 case (68.5%) died.(2) Kaplan-Meier survival analysis showed that patients who received first-witness CPR, had a lower-extremity perfusion line established, underwent IABP, achieved ROSC, had normal pH, and had an initial pupillary light reflex had a longer median survival time ( P < 0.05). (3) Univariate COX regression analysis showed that statistically differences in survival time among patients with ECMO times, hypoperfusion times, initial pupil sizes, and APACHEⅡ scores ( P < 0.05); (4) Multivariate COX regression analysis showed that APACHEⅡ score, initial pupil size, and IABP were independent predictors of survival of patients discharged from the hospital with emergency ECPR; (5) The concordance index of the COX regression model was 0.921. Conclusions:The survival model demonstrates good predictive accuracy. Healthcare professionals can use the APACHEⅡscore and initial pupil size on admission as important reference indicators to assist in determining patient prognosis, and to timely initiate IABP treatment, in conjunction with the patient’s condition, to improve the survival rate of patients discharged from the hospital.

OBJECTIVE: To investigate the protective effect and potential mechanism of tubastatin A (TubA), a specific inhibitor of histone deacetylase 6 (HDAC6), on renal and intestinal injuries after cardiopulmonary resuscitation (CPR) in swine. METHODS: Twenty-five healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 10) and TubA intervention group (n = 9) using a random number table. The porcine model of CPR was reproduced by 9-minute cardiac arrest induced by electrical stimulation via right ventricle followed by 6-minute CPR. The animals in the Sham group only underwent the regular operation including endotracheal intubation, catheterization, and anesthetic monitoring. At 5 minutes after successful resuscitation, a dose of 4.5 mg/kg of TubA was infused via the femoral vein within 1 hour in the TubA intervention group. The same volume of normal saline was infused in the Sham and CPR model groups. Venous samples were collected before modeling and 1, 2, 4, 24 hours after resuscitation, and the levels of serum creatinine (SCr), blood urea nitrogen (BUN), intestinal fatty acid binding protein (I-FABP) and diamine oxidase (DAO) in serum were determined by enzyme-linked immunoadsordent assay (ELISA). At 24 hours after resuscitation, the upper pole of left kidney and terminal ileum were harvested to detect cell apoptosis by TdT-mediated dUTP-biotin nick end labeling (TUNEL), and the expression levels of receptor-interacting protein 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) were detected by Western blotting. RESULTS: After resuscitation, renal dysfunction and intestinal mucous injury were observed in the CPR model and TubA intervention groups when compared with the Sham group, which was indicated by significantly increased levels of SCr, BUN, I-FABP and DAO in serum. However, the serum levels of SCr and DAO starting 1 hour after resuscitation, the serum levels of BUN starting 2 hours after resuscitation, and the serum levels of I-FABP starting 4 hours after resuscitation were significantly decreased in the TubA intervention group when compared with the CPR model group [1-hour SCr (μmol/L): 87±6 vs. 122±7, 1-hour DAO (kU/L): 8.1±1.2 vs. 10.3±0.8, 2-hour BUN (mmol/L): 12.3±1.2 vs. 14.7±1.3, 4-hour I-FABP (ng/L): 661±39 vs. 751±38, all P < 0.05]. The detection of tissue samples indicated that cell apoptosis and necroptosis in the kidney and intestine at 24 hours after resuscitation were significantly greater in the CPR model and TubA intervention groups when compared with the Sham group, which were indicated by significantly increased apoptotic index and markedly elevated expression levels of RIP3 and MLKL. Nevertheless, compared with the CPR model group, renal and intestinal apoptotic indexes at 24 hours after resuscitation in the TubA intervention group were significantly decreased [renal apoptosis index: (21.4±4.6)% vs. (55.2±9.5)%, intestinal apoptosis index: (21.3±4.5)% vs. (50.9±7.0)%, both P < 0.05], and the expression levels of RIP3 and MLKL were significantly reduced [renal tissue: RIP3 protein (RIP3/GAPDH) was 1.11±0.07 vs. 1.39±0.17, MLKL protein (MLKL/GAPDH) was 1.20±0.14 vs. 1.51±0.26; intestinal tissue: RIP3 protein (RIP3/GAPDH) was 1.24±0.18 vs. 1.69±0.28, MLKL protein (MLKL/GAPDH) was 1.38±0.15 vs. 1.80±0.26, all P < 0.05]. CONCLUSIONS TubA has the protective effect on alleviating post-resuscitation renal dysfunction and intestinal mucous injury, and its mechanism may be related to inhibition of cell apoptosis and necroptosis.
Male ; Animals ; Swine ; Abdominal Injuries ; Apoptosis ; Cardiopulmonary Resuscitation ; Kidney Diseases

Objective:To investigate the effect of early continuous renal replacement therapy (CRRT) within 24 h on in-hospital mortality in patients with sepsis.Methods:This study retrospectively analyzed the patients diagnosed as sepsis in the Emergency Intensive Care Unit of the First Affiliated Hospital of Wenzhou Medical University from January 2013 to December 2017. According to the prognosis, the patients were divided into the survival group and death group. The clinical baseline data of the two groups were compared, and multivariate logistic regression analysis was performed to screen out the risk factors of death in patients with sepsis and evaluate the effect of CRRT on mortality. According to whether CRRT was performed within 24 h after admission, the patients were divided into the CRRT group and non-CRRT group to compare fluid balance.Results:Among the 612 patients, 416 (67.9%) patients were male, the median age was 66 years; 362 patients survived and 250 patients died, with a mortality rate of 40.8%. Multivariate logistic regression analysis showed that the independent risk factors for death in patients with sepsis were: sex, simplified acute physiology score Ⅱ, sequential organ failure assessment, lactate, procalcitonin, and complicated with chronic obstructive pulmonary disease. Multivariate logistic regression analysis showed that patients received CRRT within 24 h had a higher risk of mortality ( OR=1.981 95% CI: 1.120-3.504, P=0.019). There was a statistically significant difference in fluid balance between the CRRT group and the non-CRRT group on the first day ( P<0.05), and there was no significant difference in total fluid balance in the first 3 days ( P>0.05). Conclusions:Early CRRT within 24 h cannot reduce the in-hospital mortality of patients with sepsis. The failure of CRRT which did not timely correct the volume overload state of patients with sepsis after fluid resuscitation may affect the outcome.

Objective:To explore the clinical characteristics of patients with paraquat mixed with diquat poisoning.Methods:The clinical data of 145 patients with paraquat mixed with diquat poisoning admitted to the Department of Emergency of the First Affiliated Hospital of Wenzhou Medical University from January 20, 2016 to March 31, 2022 were retrospectively analyzed. According to the detection results of plasma toxicants in patients with poisoning, the patients were divided into the paraquat diquat mixed group (mixed group), paraquat group (PQ group) and diquat group (DQ group). The clinical indexes, organ dysfunction, different poisoning doses and prognosis of the three groups were compared. Patients in the mixed group were divided into the survival group and death group according to their 90-day survival, and the differences of each index between the two groups were compared. Kaplan-Meier survival analysis was conducted for each index. After Log-rank test, multivariate Cox regression was used to analyze the risk factors of death in the mixed group.Results:A total of 31 patients were included in the mixed group, 92 patients in the PQ group, and 22 patients in the DQ group. There were significant differences in age, toxic dose, number of organ dysfunction, PSS score and APACHE II score among the three groups ( P<0.05). The main injured organs of the mixed group were gastrointestinal tract, kidney, liver, lung and nervous system. The proportion of organ damage in the mixed group was higher than that in the PQ group and DQ group. The white blood cell count, neutrophil count, HB, creatinine, AST, lactic acid, PT and APTT were statistically significant among the three groups ( P<0.05). In the mixed group, patients taking oral administration of < 20 mL all survived; 8 patients taking oral administration of 20 -50 mL died; 11 patients took oral administration of 51-100 mL and 8 (72.7%) died; and 10 patients took oral administration of more than 100 mL and 9 patients (90%) died. In the mixed group, patients with the concentration of diquat > 5000 ng/mL died. Among 31 patients with mixed poisoning, 30 patients (96.78%) had significantly higher concentrations of diquat than paraquat. There were no significant differences in sex, age, time from poisoning to hospitalization, ingestion amount, lymphocyte count, Hb, BNU, CK, total bilirubin, PH, and PT between the survival group and the death group ( P>0.05). Multivariate Cox regression analysis showed that the ingestion amount, plasma PQ concentration at admission, plasma DQ concentration at admission, and lactic acid were independent risk factors for death ( P<0.05). Conclusions:Paraquat mixed with diquat can cause multiple organ function damage. The main damaged organs are gastrointestinal tract, kidney, liver, lung and nervous system. Compared with PQ or DQ poisoning, mixed poisoning has a higher incidence of organ damage, a more serious condition, and a higher mortality rate. Ingestion amount, plasma PQ concentration at admission, plasma DQ concentration at admission and lactic acid were independent factors influencing the prognosis of mixed poisoning.

Objective:To explore the clinical characteristics of patients with colchicine poisoning, and analyze the risk factors affecting the prognosis of colchicine poisoning and its value in the prognostic assessment.Methods:Patients with colchicine poisoning admitted to the Emergency Intensive Care Unit of the First Affiliated Hospital of Wenzhou Medical University from December 2017 to October 2022 were retrospectively included and divided into the survival group and death group according to the 14-d outcome. The general conditions of the two groups of patients were compared, and the clinical characteristics of patients with colchicine poisoning were analyzed. The differences of laboratory indexes, electrocardiogram, cardiac ultrasound and other clinical indexes during the first admission of patients between the two groups were compared, and their value in the prognosis evaluation of patients with colchicine poisoning was explored.Results:There were 41 patients with colchicine poisoning, aged 15-85 years, including 35 males and 6 females. There were 27 patients (65.9%) in the survival group and 14 patients (34.1%) in the death group, including accumulative poisoning (58.7%) and suicide poisoning (41.3%). The main clinical manifestations of patients with colchicine poisoning were gastrointestinal symptoms (82.93%), multiple organ dysfunction (78.05%), infectious fever (73.17%), myocardial damage (48.78%), coagulation dysfunction (46.34%), and bone marrow suppression (41.46%). Intestinal obstruction (19.51%) and rhabdomyolysis (2.44%) occurred in some patients. Multivariate Logistic regression analysis showed that the increase in absolute value of QTc interval ( OR=1.028, 95% CI: 1.000~1.056, P<0.05), lactic acid ( OR=1.599, 95% CI: 1.088~2.350, P<0.05), prothrombin time ( OR=1.205, 95% CI: 1.002~1.450, P<0.05), D-dimer ( OR=1.242, 95% CI: 1.089~1.417, P<0.05), and alkaline phosphatase ( OR=1.013, 95% CI: 1.002~1.024, P<0.05) were the risk factors for the prognosis of patients with colchicine poisoning. The decrease in the absolute value of ADL score ( OR=0.947, 95% CI: 0.909~0.988, P<0.05) and indirect bilirubin ( OR=0.756, 95% CI: 0.572~0.999, P<0.05) were the protective factors for the prognosis of patients with colchicine poisoning. D-dimer (AUC=0.913), lactic acid (AUC= 0.875) and alkaline phosphatase (AUC=0.770) had predictive value for the prognosis of patients with colchicine poisoning, and their cut-off values were 8.965 mg/L, 4.05 mmol/L and 230.5 U/L, respectively. Conclusions:The patients with colchicine poisoning have multiple organ dysfunction on admission, and are in a critical condition. The early levels of D-dimer, lactic acid and alkaline phosphatase could effectively predict the prognosis of patients with colchicine poisoning.

Objective:To explore the predictive value of systemic immune inflammation index (SII) for the risk of hospital death in critically ill patients.Methods:The basic information and clinical data of critically ill patients were extracted from the Medical Information Mart for Intensive Care database-Ⅳ (MIMIC-IV) database, including demographic data, vital signs, blood routine, Logistic organ dysfunction score (Lods), Oxford acute severity of illness score (Oasis), simplified acute physiology score (Saps-Ⅱ), acute physiology score Ⅲ (APS-Ⅲ), sequential organ failure score (SOFA) and outcome. The main outcome was hospital death, and the secondary outcomes were length of hospital stay, continuous renal replacement therapy (CRRT), invasive ventilation and 1-year mortality. Patients were divided into two groups according to in-hospital death, and the differences between the groups were compared. According to the SII tripartite for inter-group comparison, the patients were further divided into three groups for comparison, and Logistic regression model was used to analyze the odd ratio ( OR) of the three groups. Results:A total of 32 450 critically ill patients were included in the study, of which 3765 died in hospital, with a mortality rate of 11.6%. ① Compared with the survival group, the SII in the death group were significantly higher ( P < 0.05). ② The mortality for the SII tripartite grouping (<817; 817~2 151; >2 151) were 8.4%, 10.2% and 16.3%, respectively, and the differences between groups were statistically significant. ③ Further, Logistic regression model analysis showed that the risk of death increased gradually with the increase of groups (the first group was the reference group, OR of the second group was 1.38, 95% CI 1.24-1.54, and OR of the third group was 2.03, 95% CI 1.83-2.24 ( P < 0.05). Conclusions:SII has a certain value in predicting hospital death in critically ill patients. It is easy to obtain and can be used for risk stratification of critically ill patients.

Objective:To explore the influencing factors of severity of upper gastrointestinal bleeding (UGIB) and to establish the early warning evaluation model in the form of line chart, so as to provide a feasible basis for emergency nurses' triage.Methods:A total of 680 UGIB patients admitted to the Emergency Department of the First Affiliated Hospital of Wenzhou Medical University from January 2019 to January 2020 were retrospectively analyzed. They were divided into a modeling group ( n=510) and a validation group ( n=170) by random number table method, and were divided into a high-risk group and a low-risk group according to the expert Consensus on Emergency Diagnosis and Treatment Procedures for Acute Upper Gastrointestinal Bleeding in 2020. The differences of various indicators between groups were compared, the factors affecting the severity of the disease were analyzed by Logistic regression, and the nomogram was drawn and validated. Results:Multivariate logistic regression analysis showed that hematemesis ( OR=3.875, 95% CI: 2.212-6.79), diabetes ( OR=2.64, 95% CI: 1.184-5.883), syncope ( OR=10.57, 95% CI: 3.675-30.403), heart rate ( OR=3.262, 95% CI: 1.753-6.068), red blood cell distribution width ( OR=3.904, 95% CI: 2.176-7.007), prothrombin time ( OR=3.665, 95% CI: 1.625-8.269), lactic acid ( OR=3.498, 95% CI: 1.926-6.354) and hemoglobin ( OR=4.984, 95% CI: 2.78-8.938) were the influencing factors of the severity of UGIB patients ( P < 0.05). The nomogram model showed good consistency and differentiation (C-index=0.903, 95% CI: 0.875-0.931), and was verified internally (C-index=0.895) and Hosmer-Lemeshow goodness-of-fit test ( P=0.7936). Externally verified C-index was 0.899 (95% CI: 0.846-0.952). The calibration curve prompt warning evaluation model had good stability and the prediction efficiency was better than the modified early warning score ( P < 0.05). Conclusions:The early warning evaluation model has a reliable predictive value, which can provide a reference for emergency medical staff to screen high-risk patients and formulate targeted nursing interventions.