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 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 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 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 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.

Objective:To explore the value of early dynamic changes of platelet count (PLT) in evaluating the prognosis of sepsis patients.Methods:A retrospective study was conducted to select sepsis patients admitted to the Emergency Intensive Care Unit (EICU) of the First Affiliated Hospital of Wenzhou Medical University from January 2013 to December 2017. The sepsis patients were divided into the survival group and death group according to the 28-day prognosis after EICU admission. The basic and clinical data of the two groups of patients were compared, and the risk factors for the 28-day prognosis of sepsis patients were screened, and the value of platelet change (ΔPLT) in the prognosis of sepsis was evaluated.Results:A total of 549 sepsis patients were included, 184 died within 28 days, and 365 survived, with a 28-day mortality rate of 33.5%. Compared with the survival group, the death group had a higher proportion of males, were older, and had more chronic diseases and tumors such as chronic obstructive pulmonary disease (COPD); simplified acute physiology score Ⅱ (SAPS-Ⅱ), sequential organ failure score (SOFA), procalcitonin, C-reactive protein, blood urea nitrogen, fibrinogen, and mean arterial pressure were lower, the PLT was lower on d1-5, the value of ΔPLT d2-5 were decreased more significantly, and the platelet to lymphocyte ratio (PLR) value was higher, and the difference was statistically significant ( P<0.05). However, there was no significant difference in mean platelet volume and platelet distribution width between the two groups (all P>0.05). Multivariate logistic regression analysis showed that COPD ( OR=4.167, 95% CI: 1.769-9.815, P<0.001), malignant tumor ( OR=1.815, 95% CI: 1.034-3.817, P=0.038), SAPS-Ⅱ score ( OR=1.071, 95% CI: 1.046-1.096, P<0.001), SOFA score ( OR=1.060, 95% CI: 1.001-1.021, P=0.041), and PLR value ( OR=1.001, 95% CI: 1.001-1.002, P<0.001) were independent risk factors affecting the 28-day prognosis of sepsis patients. PLT d1 ( OR=0.996, 95% CI: 0.995-0.998, P<0.001) was a protective factor for better prognosis in sepsis patients. The ROC curve analysis showed that the SAPS-Ⅱ score and SOFA score could predict the 28-day ICU prognosis of sepsis patients, and the SAPS-Ⅱ score had the largest area under the ROC curve (AUC=0.726). The AUC (0.678) of ΔPLT d4 was greater than those of the other days. When the optimal critical value was -26.5×10 9/L, the sensitivity was 57.8% and the specificity was 71.7%. Conclusions:The early dynamic changes of PLT are closely related to the prognosis of sepsis patients, which is worthy of clinical reference and promotion.

Objective:To investigate the role and mechanism of sodium valproate (VPA) in cardiac and cerebral injuries after cardiopulmonary resuscitation (CPR) in pigs.Methods:Twenty-five healthy male domestic pigs, weighing (37±3) kg, were randomly divided into the sham group ( n=6), CPR group ( n=10), and CPR+VPA group ( n=9). Cardiac arrest was induced by alternating current delivered via a pacing catheter in the right ventricle and untreated for 9 min, and then CPR was performed for 6 min, in which this procedure was used to establish the animal model of cardiac arrest and CPR. At 5 min after resuscitation, a dose of 150 mg/kg of VPA was infused with a pump via the femoral vein in 1 h in the CPR+VAP group. At 1 h, 2 h, 4 h and 24 h after resuscitation, blood samples were drawn from the femoral vein, and then used to measure the serum concentrations of cardiac troponin I (cTnI), creatine kinase MB (CKMB), neuron specific enolase (NSE), and S100B protein (S100B) by ELISA. At 24 h after resuscitation, the animals were euthanized, and then tissue specimens in the left myocardium and brain cortex were rapidly harvested to detect the expression levels of C/EBP homologous protein (CHOP), caspase 12, and caspase 3 by Western blot, and the rate of apoptotic cells was detected by TUNEL. Continuous variables were compared with one way analysis of variance among the three groups. Results:(1) After resuscitation, cardiac and cerebral injury biomarkers including cTnI, CKMB, NSE, and S100B in serum were significantly increased in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). The serum concentrations of cTnI and NSE starting 1 h after resuscitation and the serum concentrations of CKMB and S100B starting 2 h after resuscitation were significantly decreased in the CPR+VPA group compared to the CPR group (all P<0.05). (2) Those proteins related to cell apoptosis mediated by endoplasmic reticulum stress, including CHOP, caspase 12, and caspase 3, were significantly increased, and meanwhile apoptosis index was markedly elevated after resuscitation in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). Nevertheless, the expression levels of CHOP, caspase 12, and caspase 3 were significantly decreased, and cell apoptosis was markedly reduced in the heart and brain after resuscitation in the CPR+VPA group compared to the CPR group (all P<0.05). Conclusions:VPA can alleviate cardiac and cerebral injuries after CPR in pigs, and its mechanism may be possibly related to the inhibition of cell apoptosis mediated by endoplasmic reticulum stress.