Sivelestat improves acute lung injury by inhibiting PI3K/AKT/mTOR signaling pathway.

OBJECTIVE: To investigate the therapeutic effect and mechanism of sivelestat sodium on acute lung injury (AIL). METHODS: A rat model for ALI/acute respiratory distress syndrome (ALI/ARDS) was established. Pathological examination of lung tissue was conducted to assess lung injury. Blood gas in the arteries was measured using a blood analyzer. Changes in PaO2, PaO2/FiO2, and lung wet/dry (W/D) weight ratio were carefully compared. ELISA assay was conducted to estimate cell adhesion and inflammation response. Finally, real-time reverse transcription polymerase chain reaction and western blotting assay was used to determine the activation of PI3K/AKT/mTOR pathway. RESULTS: ARDS in vivo model was successfully constructed by LPS injection. Compared with the sham group, PaO2 and PaO2/FiO2 were significantly lower in the vehicle group, while the lung W/D ratio, the lung injury score, NE, VCAM-1, IL-8 andTNF-αwere significantly increased. After treatment with different doses of sivelestat sodium, we found PaO2, PaO2/FiO2 were prominently increased, while the lung W/D ratio, the lung injury score, NE, VCAM-1, IL-8, TNF-α levels were decreased in the dose-dependent manner. Meanwhile, compared with the vehicle group, the expression levels of Bax, PI3K, Akt and mTOR were significantly lower, and the expression of Bcl-2 was significantly higher after injection with sivelestat sodium. CONCLUSION: Sivelestat sodium has an interventional effect on ALI in sepsis by inhibiting the PI3K/AKT/mTOR signalling pathway.

Pyrroloquinoline quinone protects against murine hepatitis virus strain 3-induced fulminant hepatitis by inhibiting the Keap1/Nrf2 signaling.

Fulminant hepatitis (FH) is a life-threatening clinical liver syndrome characterized by substantial hepatocyte necrosis and severe liver damage. FH is typically associated with severe oxidative stress, inflammation, and mitochondrial dysfunction. Pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor, functions as an essential nutrient and antioxidant and reportedly inhibits oxidative stress and exerts potent anti-inflammatory effects. In the present study, we aimed to evaluate the therapeutic efficacy of PQQ in murine hepatitis virus strain 3 (MHV-3)-induced FH and examined the underlying mechanism. An MHV-3-induced FH mouse model was established for in vivo examination. Liver sinusoidal endothelial cells (LSECs) were used for in vitro experiments. Herein, we observed that PQQ supplementation significantly attenuated MHV-3-induced hepatic injury by suppressing inflammatory responses and reducing oxidative stress. Mechanistically, PQQ supplementation ameliorated MHV-3-induced hepatic damage by down-regulating the Keap1/Nrf2 signaling pathway in vivo and in vitro. Furthermore, Nrf2 small interfering RNA targeting LSECs abrogated the PQQ-mediated protective effects against MHV-3-related liver injury. Our results deepen our understanding of the hepatoprotective function of PQQ against MHV-3-induced liver injury and provide evidence that alleviating oxidative stress might afford a novel therapeutic strategy for treating FH.

Clinical effect of high-flow nasal cannula oxygen therapy combined with naloxone on severe respiratory failure in older adult patients: a randomized controlled trial.

OBJECTIVE: To analyze the clinical effect of high-flow nasal cannula (HFNC) oxygen therapy combined with naloxone on severe respiratory failure (SRF) in older adult patients. METHODS: We enrolled 96 older adult patients with SRF who were admitted to Hai'an People's Hospital between February 2019 and March 2022. The patients were divided into two groups: the control group (treated with non-invasive positive pressure ventilation combined with naloxone) and the observation group (treated with HFNC oxygen therapy combined with naloxone). The blood gas measurement, respiratory rate (RR), St. George's Respiratory Questionnaire (SGRQ) score, Clara cell secreted protein (CC16) level, tumor necrosis factor-alpha (TNF-α) level, interleukin-1 (IL-1) level, length of intensive care unit (ICU) stay, tracheal intubation rate, and 28-day mortality rate were compared between the groups. RESULTS: Blood gas measurement or RR did not differ significantly between the groups (P>0.05). The observation group showed improved outcome, including reduced partial pressure of CO2, RR, and pH, and increased partial pressure of O2 (PaO2), PaO2/fraction of inspired O2 ratio, and O2 saturation after treatment (P<0.05). Additionally, the observation group exhibited lower TNF-α level, IL-1 level, and SGRQ score, and higher CC16 level (P<0.05). The length of ICU stay, tracheal intubation rate, and 28-day mortality rate were lower in the observation group (P<0.05). CONCLUSIONS: HFNC oxygen therapy combined with naloxone in older adult patients with SRF could improve blood gas results, disease duration, tracheal intubation rate, and 28-day mortality rate. This may occur through regulation of TNF-α, IL-1, and CC16 expression.

[Analysis of clinical characteristics and risk factors of early heat stroke-related acute liver injury].

OBJECTIVE: To analyze the clinical characteristics and risk factors of early acute liver injury in patients with heat stroke (HS), and to provide basis for early identification of HS-related liver injury and its pathogenesis in clinical practice. METHODS: The clinical data of patients with HS admitted to the department of critical care medicine of Haian People's Hospital from June 2015 to August 2022 were retrospectively analyzed. The patients with HS were divided into early liver injury group and early non-liver injury group according to the occurrence of acute liver injury within 24 hours of admission. The differences of basic data, clinical data, laboratory indexes and clinical outcomes of the two groups were analyzed. Logistic regression was used to analyze the risk factors for early HS-related acute liver injury, and receiver operator characteristic (ROC) curves were drawn to evaluate their value in predicting the occurrence of early HS-related acute liver injury. RESULTS: A total of 76 patients with HS were enrolled, and 46 patients with acute liver injury, accounting for 60.53%. In the early liver injury group, 14 patients (30.43%) had elevated aminotransferase alone, 9 patients (19.57%) had elevated total bilirubin (TBil) alone, and 23 patients (50.00%) had elevated both aminotransferase and TBil. Among the patients with elevated aminotransferases, 24 patients (64.87%) had mild elevation, 5 patients (13.51%) had moderate elevation, 8 patients (21.62%) had severe elevation. Compared with the early non-liver injury group, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), arterial blood lactate (Lac), interleukin-6 (IL-6), procalcitonin (PCT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), TBil, γ-gamma glutamyl transferase (γ-GGT), lactate dehydrogenase (LDH), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB), cardiac troponin I (cTnI), myoglobin (MYO), N-terminal B-type pro-brain natriuretic peptide (NT-proBNP), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer in the early liver injury group were significantly increased, while platelet count (PLT) were significantly decreased within 24 hours after admission, the 28-day mortality was significantly increased [28.26% (13/46) vs. 6.67% (2/30)], and the differences were statistically significant (all P < 0.05). Univariate Logistic regression analysis showed that APACHE II score, SOFA score, PLT, Lac, IL-6, PCT, γ-GGT, LDH, CK, CK-MB, cTnI, MYO, PT, APTT, D-dimer were risk factors of early HS-related acute liver injury (all P < 0.05). Multivariate Logistic regression analysis showed that PLT, IL-6, and LDH were independent risk factors of early HS-related acute liver injury [odds ratio (OR) and 95% confidence interval (95%CI) were 0.986 (0.974-0.998), 1.027 (1.012-1.041), and 1.002 (1.000-1.004), all P < 0.05]. The ROC curve analysis showed that the area under the ROC curve (AUC) of PLT, IL-6 and LDH for predicting the occurrence of early HS-related acute liver injury was 0.672 (95%CI was 0.548-0.797), 0.897 (95%CI was 0.824-0.971) and 0.833 (95%CI was 0.739-0.927), respectively. IL-6 had the highest predictive value for early HS-related liver injury. When the optimal diagnostic threshold of IL-6 was 48.25 ng/L, the sensitivity was 95.7%, the specificity was 73.3%, and the predictive value of PLT was the lowest. CONCLUSIONS: The early HS-related liver injury is mainly manifested as the simultaneous elevation of aminotransferase and TBil, and most of cases are mild liver injury. PLT, IL-6 and LDH are independent risk factors of early HS-related acute liver injury.

Effects of high-flow nasal cannula oxygen therapy for patients with acute exacerbation of chronic obstructive pulmonary disease in combination with type II respiratory failure.

OBJECTIVE: To evaluate the therapeutic effects of high-flow nasal cannula (HFNC) oxygen therapy in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and type II respiratory failure. METHODS: Seventy-two patients with AECOPD and type II respiratory failure were randomly allocated to an HFNC oxygen therapy trial group or a non-invasive positive-pressure ventilator therapy (NIPPV) control group. Their arterial blood gas parameters and comfort, evaluated using a questionnaire, were compared before and after the therapeutic interventions. RESULTS: The PaCO2 and blood HCO3- concentration of both groups were significantly reduced by the treatments, whereas the pH, PaO2 and PaO2/FiO2 were increased. The PaCO2 of the experimental group was significantly lower than that of the control group following treatment. The PaO2 of the experimental group was significantly higher than that of the control group. The tracheal intubation rates of the two groups did not significantly differ. After treatment, all the indices of comfort were rated higher in the HFNC group than in the NIPPV group. CONCLUSIONS: HFNC has a good therapeutic effect in patients with AECOPD and type II respiratory failure. It improves patient comfort and has clinical value.

An investigation of the psychological stress of medical staff in Shanghai shelter hospital during COVID-19.

Objective: The purpose of this study was to assess the psychological status of medical workers from other locations who helped support the fight against COVID-19 in Shanghai and to provide a basis for psychological crisis intervention plans under designated emergencies. Methods: While supporting the Shanghai Lingang Shelter Hospital, we investigated 1,097 medical staff from other cities working in the hospital. A questionnaire comprising the general information questionnaire, health questionnaire depression scale, generalized anxiety scale, insomnia severity index scale, and mental health self-assessment questionnaire was used. Results: There were no statistically significant differences in the incidence rates of anxiety, depression, and sleep disorders among subjects of different genders, ages, and educational levels. There were statistically significant differences in the incidences of anxiety, depression, stress response, and sleep disturbance among subjects with different levels of worry about COVID-19. Conclusion: During the COVID-19 pandemic, the Lingang Shelter Hospital team experienced more psychological pressure, suggesting that medical institutions should pay attention to the mental health of frontline medical workers during COVID-19 and prepare psychological intervention measures for team members.

Relationship between Dynamic Changes of Microcirculation Flow, Tissue Perfusion Parameters, and Lactate Level and Mortality of Septic Shock in ICU.

Background: Septic shock is a common clinical critical disease with high mortality, hemodynamic instability, and easy to be complicated with multiple organ failure. The rapid progress of the patient's condition poses a serious threat to patient's safety. Aim: To investigate the relationship between the dynamic monitoring of microcirculation perfusion parameters and blood lactic acid level and the prognosis of patients with infection shock in ICU. Methods: A total of 104 patients with septic shock admitted to ICU of Affiliated Hai'an Hospital of Nantong University from February 2018 to June 2021 were selected for clinical research. According to the survival situation of patients after 28 days of treatment, they were divided into the death group (n = 48) and the survival group (n = 56). The central venous-arterial carbon dioxide partial pressure difference (Pcv-aCO2), the ratio of central venous-arterial carbon dioxide partial pressure difference to arterial central venous oxygen content difference (Pcv-aCO2/Ca-cvO2), and blood lactic acid level were retrospectively analyzed and compared between the two groups on the first, third, and seventh days after admission to ICU. The odds ratio (OR) of three indexes affecting the prognosis of patients with septic shock was analyzed by univariate and multivariate mathematical models, and the value of three indexes in predicting the prognosis of patients was analyzed by receiver operating curve (ROC). Results: Pcv-aCO2 and lactic acid in the death group were higher than those in the survival group on the 1st, 3rd, and 7th day of ICU stay (P < 0.05). The Pcv-aCO2/Ca-cvO2 of the death group was higher than that of the survival group on the 3rd and 7th day of ICU stay (P < 0.05). Logistic model results showed that age, SOFA score, APACHE II score, the number of multiple organ failure (MODS), intracranial infection, the increase of Pcv-aCO2, Pcv-aCO2/Ca-cvO2, and the increase of lactic acid were independent risk factors for death in patients with septic shock (OR values were 1.519, 1.808, 1.781, 1.912, 2.069, 1.848, 1.781, and 1.642, respectively, P < 0.05). The results showed that the AUC value of Pcv-aCO2 in predicting death was 0.943, and the sensitivity and specificity were 93.72% and 83.09%, respectively. The AUC value of Pcv-aCO2/Ca-cvO2 for predicting death was 0.887, and the sensitivity and specificity were 81.63% and 77.56%, respectively. The AUC value of lactic acid in predicting death of patients was 0.825, and the sensitivity and specificity were 71.66% and 82.09%, respectively. Conclusion: Changes of microcirculation flow tissue perfusion parameters and blood lactic acid level changes are closely related to the prognosis of patients with septic shock, which is of great value in the evaluation of the prognosis of patients with septic shock.

To Explore the Application of PDCA in Hemodialysis Center and Its Effect on the Maintenance of Internal Fistula.

Background: The survey found that in recent years, with the incidence of chronic kidney disease (CKD) increasing, some patients with CKD even progressed to end-stage renal disease. Luckily, progressive hemodialysis technology and nursing level can improve the quality of life and prognosis of patients. Objective: To explore the application of plan-do-check-adjust (PDCA) cycle in the management of nurses in hemodialysis center and its effect on the maintenance of internal fistula in patients. Methods: In this study, a randomized controlled trail (RCT) was used to select 90 patients who underwent maintenance hemodialysis in the hemodialysis center of our hospital from January 2018 to June 2021 as objects. They were divided into a PDCA group (with PDCA nursing management) and routine group (with routine nursing management) by random number table with each of 45 cases for 6 months to compare the differences of the internal fistula complications, internal fistula maintenance quality, patients' microinflammatory state, and satisfaction with nursing, as well as nursing staff's operational and theoretical performance between the two groups. Results: There was no significant difference in CRP, IL-1, TNF-α, and IL-6 levels between the two groups before intervention (P > 0.05); after that, these levels in the PDCA group were lower than those in the routine group, with statistically significant difference (P < 0.05); before intervention, there was no statistically significant difference in the qualification rate of blood flow, the awareness rate of health education, and the incidence of nursing defects between the two groups (P > 0.05); after that, the qualification rate of blood flow and the awareness rate of health education among nurses in PDCA group were higher than those in routine group, while the incidence of nursing defect accidents in the PDCA group was lower than that in routine group, and the differences were statistically significant (P < 0.05); before intervention, there was no significant difference in the complication rate between the two groups (P > 0.05); after that, the complication rate of the PDCA group was lower than that of the routine group, and the differences were statistically significant (P < 0.05); after intervention, the theoretical assessment and practical skills assessment scores of the PDCA group were higher than those of the routine group, and the differences were statistically significant (P < 0.05); after intervention, the nursing satisfaction of the PDCA group was higher than that of the routine group, and the differences were statistically significant (P < 0.05). Conclusion: The application of PDCA approach in the management of nurses in hemodialysis centers can effectively improve the quality of internal fistula management and improve the practical and theoretical level of nurses, as well as reduce the microinflammation of patients.

Thrombosis in the portal venous system caused by hypereosinophilic syndrome: A case report.

RATIONALE: Extensive thrombosis in the portal venous system caused by hypereosinophilic syndrome (HES) is rare, and there is no consensus on anticoagulant and thrombolytic treatments for arteriovenous thrombosis caused by HES. PATIENT CONCERNS: The clinical data of a patient with extensive thrombosis in his portal venous system (superior mesenteric, splenic, hepatic, and portal veins), renal artery thrombosis, and mesenteric thrombosis caused by HES with secondary gastrointestinal bleeding and intestinal necrosis were retrospectively analyzed. Before admission, his eosinophil count increased to 7.47 × 10/L, and HES had been confirmed via bone marrow cytology. The patient experienced fever, cough, abdominal pain, massive hematemesis, and hematochezia that developed in succession. Abdominal computed tomography showed portal vein and superior mesenteric vein thromboses. DIAGNOSIS: Hypereosinophilic syndrome; extensive thrombosis in the portal venous system; acute eosinophil-associated pneumonia; gastrointestinal bleeding; intestinal necrosis. INTERVENTIONS: The patient was first treated with methylprednisolone, plasma exchange/hemofiltration, and single or combined use of unfractionated heparin and argatroban for anticoagulation. He was also administered alteplase and urokinase, successively, for thrombolytic treatment. Once the thromboses finally disappeared, the patient underwent surgery to excise a necrotic intestinal canal. OUTCOMES: The thromboses disappeared with these treatments, and the patient recovered after the necrotic intestinal canal was excised. LESSONS: The clinical manifestations of HES are complex and varied, and this condition can cause severe and extensive arteriovenous thrombosis. Anticoagulation therapy and thrombolysis are necessary interventions, and appear to be safe and effective.