Objective To study the effect of stachydrine on cardiomyocyte damage induced by high glucose(HG)and its regulation of Hippo-Yes-associated protein(YAP)signaling pathway.Methods Rat myocardial cells H9C2 were stimulated by HG with 30 mmol/L glucose to establish the myocardial cell injury model,and then treated with 0.05,0.10,0.15,0.20 mmol/L of stachydrine and their activities were detected by CCK-8 method,and the action concentration of stachycarine was screened.Then H9C2 was grouped into control(ctrl)group,HG group,low concentration stachydrine group,high concentration stachydrine group,and high concentration stachydrine+Hippo-YAP signaling pathway inhibitor(TDI-011536)group.Except for the ctrl group cultured with 5 mmol/L glucose,the other 4 groups were cultured with 30 mmol/L glucose,and the low and high concentration stachydrine groups were cultured with 0.05 and 0.10 mmol/L threonine for 24h,respectively.The high concentration stachydrine+TDI-011536 group were cultured with 0.10 mmol/L stachydrine and 3.00 μmol/L TDI-011536 for 24h.CCK-8 method was applied to detect cell proliferation.Flow cytometry was applied to detect apoptosis.ELISA were applied to detect the level of malondialdehyde(MDA)and superoxide dismutase(SOD).Western blot was applied to detect the level of phosphorylated YAP(p-YAP),YAP,proliferating cell nuclear antigen(PCNA),and B-cell lymphoma-2(Bcl-2)proteins.Results Compared with ctrl group,the survival rate of H9C2 cells induced by HG was significantly increased by 0.05,0.10,0.15,0.20 mmol/L stachydrine treatment,and the differences were statistically significant(t=8.32～29.67,all P<0.01).The 50%inhibitory concentration(IC50)value of stachydrine was about 0.09 mmol/L,and the concentrations of 0.05 mmol/L and 0.10 mmol/L close to and lower than IC50 were selected as the concentrations of hydrostachyine for subsequent experiments.Compared with the ctrl group,the survival rate in HG group was significantly decreased(t=44.32,P<0.01).Compared with HG group,the cell survival rate of low concentration stachydrine group and high concentration stachydrine group was significantly increased(t=10.06,21.66,all P<0.01).Compared with the high concentration stachydrine group,the cell survival rate in the high-concentration stachydrine+TDI-011536 group was significantly decreased(t=9.54,P<0.01),and the differences were statistically significant,respectively.Compared with ctrl group,the apoptosis rate of HG group was significantly increased(t=36.74,P<0.01).Compared with HG group,the apoptosis rate of low concentration stachydrine group and high concentration stachydrine group was significantly decreased(t=11.04,26.78,all P<0.01).Compared with the high concentration threonine group,the apoptosis rate of the high concentration stachydrine+TDI-011536 group was significantly increased(t=9.96,P<0.01),and the differences were statistically significant,respectively.Compared with ctrl group,SOD level in HG group was significantly decreased,MDA levels were significantly increased(t=18.85,29.12,all P<0.01).Compared with HG group,SOD level were significantly increased in low concentration stachydrine groups and high concentration stachydrine groups(t=6.59,9.86,all P<0.01),MDA level were significantly decreased(t=13.45,23.36,all P<0.01).Compared with the high concentration stachydrine group,the SOD level in the high concentration hydrostatin+TDI-011536 group was significantly decreased.MDA levels were significantly increased,and the differences were statistically significant(t=5.30,6.98,all P<0.01),respectively.Compared with ctrl group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein were significantly decreased,and the level of YAP protein was significantly increased(t=15.36～45.00,all P<0.01).Compared with HG group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein were significantly increased in low concentration stachydrine group and high concentration stachydrine group,the level of YAP protein levels were significantly decreased(t=5.51～25.15,all P<0.01).Compared with the high concentration stachydrine group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein in the high concentration hydrothreonine+TDI-011536 group were significantly decreased,the level of YAP protein significantly increased,the differences were statistically significant(t=4.27～11.25,all P<0.05).Conclusion Stachydrine may inhibit oxidative stress and apoptosis by activating Hippo-YAP signaling pathway,thereby ameliorating HG-induced myocardial cell damage.

Objective To study the effect of stachydrine on cardiomyocyte damage induced by high glucose(HG)and its regulation of Hippo-Yes-associated protein(YAP)signaling pathway.Methods Rat myocardial cells H9C2 were stimulated by HG with 30 mmol/L glucose to establish the myocardial cell injury model,and then treated with 0.05,0.10,0.15,0.20 mmol/L of stachydrine and their activities were detected by CCK-8 method,and the action concentration of stachycarine was screened.Then H9C2 was grouped into control(ctrl)group,HG group,low concentration stachydrine group,high concentration stachydrine group,and high concentration stachydrine+Hippo-YAP signaling pathway inhibitor(TDI-011536)group.Except for the ctrl group cultured with 5 mmol/L glucose,the other 4 groups were cultured with 30 mmol/L glucose,and the low and high concentration stachydrine groups were cultured with 0.05 and 0.10 mmol/L threonine for 24h,respectively.The high concentration stachydrine+TDI-011536 group were cultured with 0.10 mmol/L stachydrine and 3.00 μmol/L TDI-011536 for 24h.CCK-8 method was applied to detect cell proliferation.Flow cytometry was applied to detect apoptosis.ELISA were applied to detect the level of malondialdehyde(MDA)and superoxide dismutase(SOD).Western blot was applied to detect the level of phosphorylated YAP(p-YAP),YAP,proliferating cell nuclear antigen(PCNA),and B-cell lymphoma-2(Bcl-2)proteins.Results Compared with ctrl group,the survival rate of H9C2 cells induced by HG was significantly increased by 0.05,0.10,0.15,0.20 mmol/L stachydrine treatment,and the differences were statistically significant(t=8.32～29.67,all P<0.01).The 50%inhibitory concentration(IC50)value of stachydrine was about 0.09 mmol/L,and the concentrations of 0.05 mmol/L and 0.10 mmol/L close to and lower than IC50 were selected as the concentrations of hydrostachyine for subsequent experiments.Compared with the ctrl group,the survival rate in HG group was significantly decreased(t=44.32,P<0.01).Compared with HG group,the cell survival rate of low concentration stachydrine group and high concentration stachydrine group was significantly increased(t=10.06,21.66,all P<0.01).Compared with the high concentration stachydrine group,the cell survival rate in the high-concentration stachydrine+TDI-011536 group was significantly decreased(t=9.54,P<0.01),and the differences were statistically significant,respectively.Compared with ctrl group,the apoptosis rate of HG group was significantly increased(t=36.74,P<0.01).Compared with HG group,the apoptosis rate of low concentration stachydrine group and high concentration stachydrine group was significantly decreased(t=11.04,26.78,all P<0.01).Compared with the high concentration threonine group,the apoptosis rate of the high concentration stachydrine+TDI-011536 group was significantly increased(t=9.96,P<0.01),and the differences were statistically significant,respectively.Compared with ctrl group,SOD level in HG group was significantly decreased,MDA levels were significantly increased(t=18.85,29.12,all P<0.01).Compared with HG group,SOD level were significantly increased in low concentration stachydrine groups and high concentration stachydrine groups(t=6.59,9.86,all P<0.01),MDA level were significantly decreased(t=13.45,23.36,all P<0.01).Compared with the high concentration stachydrine group,the SOD level in the high concentration hydrostatin+TDI-011536 group was significantly decreased.MDA levels were significantly increased,and the differences were statistically significant(t=5.30,6.98,all P<0.01),respectively.Compared with ctrl group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein were significantly decreased,and the level of YAP protein was significantly increased(t=15.36～45.00,all P<0.01).Compared with HG group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein were significantly increased in low concentration stachydrine group and high concentration stachydrine group,the level of YAP protein levels were significantly decreased(t=5.51～25.15,all P<0.01).Compared with the high concentration stachydrine group,the level of p-YAP,p-YAP/YAP,PCNA,Bcl-2 protein in the high concentration hydrothreonine+TDI-011536 group were significantly decreased,the level of YAP protein significantly increased,the differences were statistically significant(t=4.27～11.25,all P<0.05).Conclusion Stachydrine may inhibit oxidative stress and apoptosis by activating Hippo-YAP signaling pathway,thereby ameliorating HG-induced myocardial cell damage.

Objective:To explore the diagnostic accuracy of muscle ultrasound and plasma monocyte chemoattractant protein-1 (MCP-1) for ICU-acquired weakness (ICU-AW) in patients with sepsis.Methods:A prospective observational study was conducted. Patients with sepsis admitted to the intensive care unit (ICU) of Henan Provincial People's Hospital from April 2021 to October 2021 were enrolled. The demographic data were collected. The enrolled patients were evaluated with Medical Research Council (MRC) score every day until discharged from ICU. During this period, patients with total MRC score < 48 (for two consecutive times and a time interval of 24 hours) were divided into ICU-AW group, those with total MRC score ≥ 48 were served as non-ICU-AW group. On the 1st, 4th and 7th day following admission into ICU, ultrasound was used to measure the muscle linear thickness of the rectus femoris (RF-MLT), the cross sectional area of the rectus femoris (RF-CSA) and the muscle linear thickness of the vastus intermedius muscle (VI-MLT). And meanwhile, the plasmas samples of patients were collected to measure MCP-1 concentration by enzyme-linked immunosorbent assay (ELISA). The difference of each index was compared between the ICU-AW group and the non-ICU-AW group. The risk factors of ICU-AW in patients with sepsis were analyzed by binary Logistic regression. Besides, receiver operator characteristic curve (ROC curve) was plotted, the diagnostic value of ultrasound parameters and plasma MCP-1 level for ICU-AW in patients with sepsis was analyzed.Results:A total of 99 septic patients were enrolled, with 68 patients in the ICU-AW group and 31 patients in the non-ICU-AW group. Compared with the patients in the ICU-AW group, the patients in the non-ICU-AW group tended to be older, and had higher sequential organ failure assessment (SOFA) score, higher acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, higher rates of septic shock, higher blood lactic acid and lower Glasgow coma score (GCS). Binary Logistic regression analysis showed that APACHEⅡ score and septic shock were the risk factors of ICU-AW for septic patients [odds ratio ( OR) and 95% confidence interval (95% CI) were 1.310 (1.138-1.509) and 0.232 (0.072-0.746), respectively, both P < 0.05]. The RF-MLT, RF-CSA and VI-MLT on the 1st, 4th and 7th ICU day was falling over time. Compared with the patients in the ICU-AW group, the patients in the non-ICU-AW group had smaller RF-MLT on the 7th day [cm: 0.32 (0.22, 0.47) vs. 0.45 (0.34, 0.63), P < 0.05] and higher 7-day RF-CSA atrophy rate [25.85% (10.37%, 34.28%) vs. 11.65% (2.28%, 22.41%), P < 0.05]. According to ROC curve analysis, 7-day RF-MLT had diagnostic value for ICU-AW of septic patients. Area under ROC curve (AUC) was 0.688 (95% CI was 0.526-0.849); when the cut-off value was 0.41 cm, the sensitivity and the specificity were 66.7% and 68.4%. The levels of plasma MCP-1 in the ICU-AW group were significantly higher than those in the non-ICU-AW group on the 1st, 4th and 7th day. ROC curve analysis showed that the plasma MCP-1 levels on the 1st, 4th and 7th day played a significant role to diagnose ICU-AW for septic patients, the AUC and 95% CI were 0.732 (0.629-0.836), 0.865 (0.777-0.953), 0.891 (0.795-0.986), respectively. When the cut-off values were 206.3, 410.9, 239.5 ng/L, the sensitivity was 87.1%, 64.0%, 82.4%, and the specificity was 54.4%, 96.1%, 86.2%, respectively. Conclusion:The muscle mass parameters on the 7th day of bedside ultrasound and plasma MCP-1 levels had certain diagnostic values for ICU-AW in patients with sepsis.

Objective:To explore the risk factors of intensive care unit acquired weakness (ICUAW) in patients with sepsis, and to evaluate the predictive value of each risk factor for ICUAW.Methods:A case control study was conducted, 60 septic patients admitted to the intensive care unit (ICU) of Henan Provincial People's Hospital from October 20, 2020 to February 20, 2021 were enrolled. The patients were divided into two groups: sepsis ICUAW group and sepsis non-ICUAW group. The data of gender, age, body mass index (BMI), acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, complications, mechanical ventilation, duration of ICUAW, length of stay in ICU, fasting blood glucose, blood lactic acid (Lac), procalcitonin (PCT), C-reactive protein (CRP), sequential organ failure assessment (SOFA) score, outcome, antimicrobial agent, glucocorticoid, sedatives and analgesics drugs and vasoactive drugs were collected. Risk factors were screened by univariate Logistic regression analysis, and odds ratio ( OR) was adjusted by multivariate binary logistic regression, P < 0.05 was considered as independent risk factors. Finally, the receiver operating characteristic curve (ROC curve) was drawn to analyze the predictive value of independent risk factors. Results:The APACHEⅡ score of the sepsis ICUAW group was significantly higher than that of the sepsis non-ICUAW group (23.05±8.17 vs. 15.33±4.89, P < 0.05), the total length of stay in the ICU was significantly longer than that of the sepsis non-ICUAW group (days: 15.1±9.2 vs. 8.5±3.4, P < 0.05), the improvement rate of patients was significantly lower than that of the sepsis non-ICUAW group [45.0% (9/20) vs. 95.0% (38/40), P < 0.05]. After univariate Logistic regression and multicollinearity test analysis, 7 factors including APACHEⅡ score, average SOFA score, blood lactic acid, proportion of mechanical ventilation, sedatives and analgesics drugs, type of antibiotics and type of vasoactive drugs were included in the binary Logistic regression model [ OR: 1.21, 2.05, 2.26, 0.21, 1.54, 2.07, 1.38, 95% confidence interval (95% CI): 1.09-1.35, 1.42-2.94, 1.12-4.57, 0.05-0.66, 1.03-2.29, 1.27-3.37, 0.96-2.00, all P < 0.05]. Hosmer-Lemchaw test P = 0.901, and the correct percentage of prediction was 85%, indicating good model fit. Multivariate binary Logistic regression analysis showed that APACHEⅡ score and average SOFA score were independent risk factors for the occurrence of ICUAW in septic patients (APACHEⅡscore: OR = 1.17, 95% CI was 1.004-1.376, P = 0.044; average SOFA score: OR = 1.86, 95% CI was 1.157-2.981, P = 0.01). ROC curve analysis showed that the mean value of APACHEⅡ score, average SOFA score and their combined detection had a certain predictive value for the occurrence of ICUAW in sepsis patients, areas under ROC curve (AUC) were 0.787, 0.881, 0.905, 95% CI was 0.646-0.928, 0.791-0.972, 0.828-0.982, all P < 0.05. When the cut-off value was 19.500, 6.225, 0.375, the sensitivity was 75%, 90%, 90%, and the specificity were 80%, 80%, 85%, respectively. Conclusion:APACHEⅡ score and average SOFA score can be used as independent risk factors for the occurrence of ICUAW in sepsis, and their combined predictive value is better than that of individual index.

Objective: To explore the usability of regional saturation of cerebral oxygenation (rScO₂) combined with percentage of α variability (PAV) in predicting brain function prognosis in patients with traumatic brain injury (TBI). Methods: A retrospective analysis was conducted. The clinical data of patients with TBI who were monitored rScO₂ and bedside quantitative electroencephalogram (qEEG) admitted to intensive care unit (ICU) of Henan Provincial People's Hospital from August 2018 to July 2019 were collected. The rScO₂, PAV, and Glasgow coma scale (GCS) score were recorded within 72 hours after the TBI. The primary prognostic indicator was the 3-month Glasgow outcome score (GOS) score. The differences between the two groups of poor prognosis of brain function (GOS score 1-3) and good prognosis (GOS score 4-5) were compared. Binary multivariate Logistic regression analysis was used to analyze the correlation between rScO₂, PAV, GCS score and the prognosis of brain function in patients with TBI. In addition, receiver operating characteristic (ROC) curve was plotted to analyze the predicting value of rScO₂ and PAV only or combination for prognosis of brain function. Results: A total of 42 patients with TBI were enrolled in the study, with rScO₂≥0.60 (grade Ⅰ) in 14 patients, 0.50≤rScO₂ < 0.60 (grade Ⅱ) in 16 patients, and rScO₂ < 0.50 (grade Ⅲ) in 12 patients. PAV 3-4 scores (grade Ⅰ) were detected in 16 patients, 2 scores (grade Ⅱ) in 17 patients, and 1 score (grade Ⅲ) in 9 patients. GCS score 9-14 (grade Ⅰ) were observed in 13 patients, 4-8 (grade Ⅱ) in 23 patients, and 3 (grade Ⅲ) in 6 patients; 18 patients had poor prognosis and 24 had good one. The rScO₂, PAV and GCS scores of the poor-prognosis group were significantly higher than those in the good-prognosis group [rScO₂ with grade Ⅲ: 55.6% (10/18) vs. 8.3% (2/24), PAV with grade Ⅲ: 38.9% (7/18) vs. 8.4% (2/24), GCS score with grade Ⅲ: 27.7% (5/18) vs. 4.1% (1/24)] with significant differences (all P < 0.05). There was no significant difference in other general data including gender, age, total length of hospital stay or acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score between the two groups. Binary multivariate Logistic regression analysis showed that rScO₂ and PAV were independent risk factors for prognosis of brain in patients with TBI [rScO₂: odds ratio (OR) = 4.656, 95% confidence interval (95%CI) was 1.071-20.233, P = 0.040; PAV: OR = 3.525, 95%CI was 1.044-11.906, P = 0.042]. ROC curve analysis showed that both of rScO₂ and PAV had predictive value for the prognosis of brain function in patients with TBI (AUC was 0.796 and 0.780, respectively, both P < 0.01), and rScO₂ combined with PAV had higher predictive value with the AUC of 0.851 (P < 0.01) than rScO₂ or PAV alone, the sensitivity was 94.4% and the specificity was 62.5%. Conclusions rScO₂ and PAV were associated with early brain function prognosis in patients with TBI. The combination of two monitoring indicators can reliably assess the prognosis of brain function in patients with TBI.

OBJECTIVE: To explore the usability of regional saturation of cerebral oxygenation (rScO₂) combined with percentage of α variability (PAV) in predicting brain function prognosis in patients with traumatic brain injury (TBI). METHODS: A retrospective analysis was conducted. The clinical data of patients with TBI who were monitored rScO₂ and bedside quantitative electroencephalogram (qEEG) admitted to intensive care unit (ICU) of Henan Provincial People's Hospital from August 2018 to July 2019 were collected. The rScO₂, PAV, and Glasgow coma scale (GCS) score were recorded within 72 hours after the TBI. The primary prognostic indicator was the 3-month Glasgow outcome score (GOS) score. The differences between the two groups of poor prognosis of brain function (GOS score 1-3) and good prognosis (GOS score 4-5) were compared. Binary multivariate Logistic regression analysis was used to analyze the correlation between rScO₂, PAV, GCS score and the prognosis of brain function in patients with TBI. In addition, receiver operating characteristic (ROC) curve was plotted to analyze the predicting value of rScO₂ and PAV only or combination for prognosis of brain function. RESULTS: A total of 42 patients with TBI were enrolled in the study, with rScO₂ ≥ 0.60 (grade I) in 14 patients, 0.50 ≤ rScO₂ < 0.60 (grade II) in 16 patients, and rScO₂ < 0.50 (grade III) in 12 patients. PAV 3-4 scores (grade I) were detected in 16 patients, 2 scores (grade II) in 17 patients, and 1 score (grade III) in 9 patients. GCS score 9-14 (grade I) were observed in 13 patients, 4-8 (grade II) in 23 patients, and 3 (grade III) in 6 patients; 18 patients had poor prognosis and 24 had good one. The rScO₂, PAV and GCS scores of the poor-prognosis group were significantly higher than those in the good-prognosis group [rScO₂ with grade III: 55.6% (10/18) vs. 8.3% (2/24), PAV with grade III: 38.9% (7/18) vs. 8.4% (2/24), GCS score with grade III: 27.7% (5/18) vs. 4.1% (1/24)] with significant differences (all P < 0.05). There was no significant difference in other general data including gender, age, total length of hospital stay or acute physiology and chronic health evaluation II (APACHE II) score between the two groups. Binary multivariate Logistic regression analysis showed that rScO₂ and PAV were independent risk factors for prognosis of brain in patients with TBI [rScO₂: odds ratio (OR) = 4.656, 95% confidence interval (95%CI) was 1.071-20.233, P = 0.040; PAV: OR = 3.525, 95%CI was 1.044-11.906, P = 0.042]. ROC curve analysis showed that both of rScO₂ and PAV had predictive value for the prognosis of brain function in patients with TBI (AUC was 0.796 and 0.780, respectively, both P < 0.01), and rScO₂ combined with PAV had higher predictive value with the AUC of 0.851 (P < 0.01) than rScO₂ or PAV alone, the sensitivity was 94.4% and the specificity was 62.5%. CONCLUSIONS rScO₂ and PAV were associated with early brain function prognosis in patients with TBI. The combination of two monitoring indicators can reliably assess the prognosis of brain function in patients with TBI.
APACHE ; Brain ; Brain Injuries, Traumatic/diagnosis* ; Humans ; Prognosis ; Retrospective Studies