Objective:To explore the mechanism of osteoclast stimulatory transmembrane protein (OC-STAMP) overexpression on epithelial-mesenchymal transition (EMT) .Methods:In April 2021, mice alveolar type Ⅱ epithelial cells MLE-12 were divided into five groups: overexpression control group (NC group), Ocstamp overexpression group (over- Ocstamp group), Fasudil intervention group (over- Ocstamp+Fasudil group), silence control group (si-NC group), Ocstamp silence group (si- Ocstamp group). The protein expressions of OC-STAMP, epithelial marker protein-E-cadherin (E-cad), interstitial marker protein-α-smooth muscle actin (α-SMA), Ras homolog gene family member A (RhoA), Rho GDP dissociation inhibitor α (Rho GDIα), Rho-associated protein kinase (ROCK), phosphate myosin phosphatase (p-MYPT) were examined by Western blotting and Immunocytochemical staining. The filamentous actin (F-actin) was detected by Phalloidin method. t test was used to compare the relative expression of each protein between the two groups. Results:Western blotting and Immunocytochemical staining showed that compared with the NC group, the expression level of E-cad was down-regulated, while the expression levels of α-SMA, Rho GDIα, RhoA, ROCK, p-MYPT were increased, and F-actin expression was enhanced in the over- Ocstamp group. The differences were statistically significant ( P<0.05). There were no significant differences in E-cad and α-SMA protein expression in si- Ocstamp group compared with si-NC group ( P>0.05). Compared with over- Ocstamp group, the expression level of E-cad protein in over- Ocstamp+Fasudil group was up-regulated, the expression levels of α-SMA, Rho GDIα, RhoA, ROCK and p-MYPT protein were decreased, and F-actin expression was weakened, with statistical significance ( P<0.05) . Conclusion:OC-STAMP overexpression in alveolar type Ⅱ epithelial cells may induce actin cytoskeleton remodeling through activation of Rho GDIα/RhoA/ROCK signaling pathway, thus promoting EMT.

Objective:The regional emergency system needs to maintain normal operation in disasters and sudden public health events, ensuring the timely treatment of critically ill patients, and also bearing the responsibility of ensuring various large-scale sports events. This article explores the practice of the "three-dimensional closed-loop" emergency system in the guarantee of the Hangzhou Asian Games in Wenzhou.Methods:After analyzing and integrating existing medical resources, the First Hospital Affiliated to Wenzhou Medical University conducted a two-year medical emergency exercise in a simulated urban road and natural water environment, and improved and optimized the weak links in the medical security system.Results:The hospital established a "three-dimensional closed-loop" emergency system and completed the medical support tasks for the Asian Games. The "three-dimensional closed-loop" emergency rescue system adopted a three-dimensional management team that combined a decentralized organizational structure and a professional medical team, and also has a land-air-sea emergency rescue team. By combining manpower and information technology, the system could provide "4R" medical services: real-time perception of medical emergencies in venues, rapid assessment of the patient's condition, rapid transfer of patients and rapid deployment of medical forces within the hospital. In addition, closed-loop management of the hospital's diagnosis and treatment process improved patients' satisfaction during the treatment process.Conclusions:The the "three-dimensional closed-loop" emergency system provided a strong guarantee for the successful holding of the Hangzhou Asian Games in Wenzhou and also accumulates experience for future urban emergency rescue.

ObjectiveTo investigate the influence of interference tasks and age on gait characteristics and task costs of children aged three to eight years. MethodsFrom April to August, 2021, 200 children from a kindergarten and primary school in Cangzhou, Hebei were enrolled to collect gait spatiotemporal parameters and kinematics data with infrared motion capture system; ground reaction force was collected with the Kistler force platform and simulated with Anybody 7.0, as walking naturally (standard gait), answering question (cognitive gait) and crossing obstacle (obstacle-crossing gait). ResultsA total of 182 children finished the test. The main effect of task was significant on spatiotemporal parameters (F > 5.167, P < 0.01), as well as age (F > 2.321, P < 0.05), except on stride width and speed; while the interaction effect of task and age was significant on double stance phase, single stance phase and step length (F > 3.040, P < 0.01). The main effect of task was significant on kinematics data (F > 83.019, P < 0.001), as well as age (F > 2.359, P < 0.05), except on range of motion of knee and maximum angular velocity of ankle; while the interaction effect of task and age was significant (F > 2.066, P < 0.05), except on range of motion of hip. The main effect of task and age was significant on kinetic parameters (F > 4.032, P < 0.05); while the interaction effect of task and age was significant (F > 2.189, P < 0.05), except on the strength of medial soleus, lateral gastrocnemius, medial gastrocnemius and tibialis anterior. The coefficient of variation was the most for cognitive gait, and then for the obstacle-crossing gait and standard gait. The main effect of task and age was significant on the cost of task for stride length and speed (F > 3.368, P < 0.01), while the interaction effect was not significant. ConclusionGait of early childhood is influenced by interference tasks and age. Under interference tasks, gait cycle increases, while single stance phase, stride length, frequency and speed decrease; and task costs increase, and overall gait stability decrease. Cognitive tasks impact on gait greater than obstacle crossing, which may be due to the higher costs of tasks. In terms of age, gait exhibits a non-linear age trend.

Objective:To explore the mechanism of osteoclast stimulatory transmembrane protein (OC-STAMP) overexpression on epithelial-mesenchymal transition (EMT) .Methods:In April 2021, mice alveolar type Ⅱ epithelial cells MLE-12 were divided into five groups: overexpression control group (NC group), Ocstamp overexpression group (over- Ocstamp group), Fasudil intervention group (over- Ocstamp+Fasudil group), silence control group (si-NC group), Ocstamp silence group (si- Ocstamp group). The protein expressions of OC-STAMP, epithelial marker protein-E-cadherin (E-cad), interstitial marker protein-α-smooth muscle actin (α-SMA), Ras homolog gene family member A (RhoA), Rho GDP dissociation inhibitor α (Rho GDIα), Rho-associated protein kinase (ROCK), phosphate myosin phosphatase (p-MYPT) were examined by Western blotting and Immunocytochemical staining. The filamentous actin (F-actin) was detected by Phalloidin method. t test was used to compare the relative expression of each protein between the two groups. Results:Western blotting and Immunocytochemical staining showed that compared with the NC group, the expression level of E-cad was down-regulated, while the expression levels of α-SMA, Rho GDIα, RhoA, ROCK, p-MYPT were increased, and F-actin expression was enhanced in the over- Ocstamp group. The differences were statistically significant ( P<0.05). There were no significant differences in E-cad and α-SMA protein expression in si- Ocstamp group compared with si-NC group ( P>0.05). Compared with over- Ocstamp group, the expression level of E-cad protein in over- Ocstamp+Fasudil group was up-regulated, the expression levels of α-SMA, Rho GDIα, RhoA, ROCK and p-MYPT protein were decreased, and F-actin expression was weakened, with statistical significance ( P<0.05) . Conclusion:OC-STAMP overexpression in alveolar type Ⅱ epithelial cells may induce actin cytoskeleton remodeling through activation of Rho GDIα/RhoA/ROCK signaling pathway, thus promoting EMT.

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.

Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) is one of important kinases in inflammation to phosphorylate inhibitor of nuclear factor kappa-B (IκBα) and then activate nuclear factor kappa-B (NF-κB). Inhibition of IKKβ has been a therapeutic strategy for inflammatory and autoimmune diseases. Here we report that IKKβ is constitutively activated in healthy donors and healthy Ikkβ ^C46A (cysteine 46 mutated to alanine) knock-in mice although they possess intensive IKKβ-IκBα-NF-κB signaling activation. These indicate that IKKβ activation probably plays homeostatic role instead of causing inflammation. Compared to Ikkβ ^WT littermates, lipopolysaccharides (LPS) could induce high mortality rate in Ikkβ ^C46A mice which is correlated to breaking the homeostasis by intensively activating p-IκBα-NF-κB signaling and inhibiting phosphorylation of 5' adenosine monophosphate-activated protein kinase (p-AMPK) expression. We then demonstrated that IKKβ kinase domain (KD) phosphorylates AMPKα1 via interacting with residues Thr183, Ser184, and Thr388, while IKKβ helix-loop-helix motifs is essential to phosphorylate IκBα according to the previous reports. Kinase assay further demonstrated that IKKβ simultaneously catalyzes phosphorylation of AMPK and IκBα to mediate homeostasis. Accordingly, activation of AMPK rather than inhibition of IKKβ could substantially rescue LPS-induced mortality in Ikkβ ^C46A mice by rebuilding the homeostasis. We conclude that IKKβ activates AMPK to restrict inflammation and IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.

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.