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Podocytes, dynamic polarized cells wrapped around glomerular capillaries, are an essential component of the glomerular filtration barrier. BK channels consist of one of the slit diaphragm (SD) proteins in podocytes, interact with the actin cytoskeleton, and play vital roles in glomerular filtration. Mechanistic target of rapamycin (mTOR) complexes regulate expression of SD proteins, as well as cytoskeleton structure, in podocytes. However, whether mTOR complexes regulate podocyte BK channels is still unclear. Here, we investigated the mechanism of mTOR complex regulation of BK channels via real-time PCR, western blot, immunofluorescence, and patch clamping. Inhibiting mTORC1 with rapamycin or downregulating Raptor had no significant effect on BK channel mRNA and protein levels and bioactivity. However, the dual inhibitor of mTORC1 and mTORC2 AZD8055 and short hairpin RNA targeting Rictor downregulated BK channel mRNA and protein levels and bioactivity. In addition, MK2206, GF109203X, and GSK650394, which are inhibitors of Akt, PKCα, and SGK1, respectively, were employed to test the downstream signaling pathway of mTORC2. MK2206 and GF109203X had no effect on BK channel protein levels. MK2206 caused an obvious decrease in the current density of the BK channels. Moreover, GSK650394 downregulated the BK channel protein and mRNA levels. These results indicate mTORC2 not only regulates the distribution of BK channels through Akt, but also modulates BK channel protein expression via SGK1 in podocytes. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy of arterial partial pressure of oxygen (PaO 2 ), procalcitonin (PCT) combined with ROX index in predicting the timing of tracheal intubation in patients with acute severe pancreatitis (SAP)., Methods: A case-control study was conducted. A total of 148 patients with SAP admitted to Hunan Provincial People's Hospital from January 2019 to December 2022 were selected as the research objects. According to whether endotracheal intubation was used after admission during hospitalization, the patients were divided into the intubation group (102 cases) and non-intubation group (46 cases). Gender, age, white blood cell count (WBC), lymphocyte count (LYM), platelet count (PLT), C-reactive protein (CRP), hemoglobin (Hb), PCT, PaO 2 , arterial partial pressure of carbon dioxide (PaCO 2 ), arterial bicarbonate ion (HCO 3 - ) 1 day after admission, arterial lactic acid (Lac), lactate dehydrogenase (LDH), heart rate (HR), respiratory rate (RR), pulse oxygen saturation (SpO 2 ), oxygenation index (PaO 2 /FiO 2 ), blood pressure, worst ROX index (ROX index = SpO 2 /FiO 2 /RR) within 30 minutes of admission and 30 minutes before intubation of the two groups were measured. Multivariate Logistic regression was used to analyze the independent risk factors for the timing of endotracheal intubation in patients with SAP. The receiver operator characteristic curve (ROC curve) was used to determine the optimal predictive cut-off value for endotracheal intubation., Results: There were no significant differences in age, gender, WBC, LYM, CRP, Hb, LDH, HR and blood pressure at admission between the two groups. The PLT, Lac, PCT and RR in the intubation group were significantly higher than those in the un-intubation group, and HCO 3 - , PaO 2 , SpO 2 , PaO 2 /FiO 2 , the worst ROX index within 30 minutes after admission and 30 minutes before intubation were significantly lower than those in the non-intubation group (all P < 0.05). Logistic regression analysis showed that the worst ROX index within 30 minutes before intubation was the largest negative influencing factor for the timing of tracheal intubation in SAP patients [odds ratio (OR) = 0.723, 95% confidence interval (95%CI) was 0.568-0.896, P = 0.000], followed by PaO 2 (OR = 0.872, 95%CI was 0.677-1.105, P < 0.001). PCT was the positive influencing factor (OR = 1.605, 95%CI was 1.240-2.089, P < 0.001). ROC curve analysis showed that the area under the ROC curve (AUC) of PaO 2 , PCT, the worst ROX index within 30 minutes before intubation and the combination to evaluate the tracheal intubation time of patients with SAP were 0.715, 0.702, 0.722 and 0.808, the sensitivity was 78.1%, 75.0%, 81.5% and 89.3%, the specificity was 66.7%, 59.0%, 73.2% and 86.4%, and the best cut-off value was 60.23 mmHg (1 mmHg ≈ 0.133 kPa), 2.72 μg/L, 4.85, and 0.58, respectively. The AUC of the combination of PaO 2 , PCT and the worst ROX index within 30 minutes before intubation predicted the timing of tracheal intubation in patients with SAP was significantly greater than using each index alone (all P < 0.01)., Conclusions: The worst ROX index within 30 minutes before intubation combined with PaO 2 and PCT is helpful for clinicians to make a decision for tracheal intubation in patients with SAP.

Podocytes, dynamic polarized cells wrapped around glomerular capillaries, are an essential component of the glomerular filtration barrier. BK channels consist of one of the slit diaphragm (SD) proteins in podocytes, interact with the actin cytoskeleton, and play vital roles in glomerular filtration. Mechanistic target of rapamycin (mTOR) complexes regulate expression of SD proteins, as well as cytoskeleton structure, in podocytes. However, whether mTOR complexes regulate podocyte BK channels is still unclear. Here, we investigated the mechanism of mTOR complex regulation of BK channels via real-time PCR, western blot, immunofluorescence, and patch clamping. Inhibiting mTORC1 with rapamycin or downregulating Raptor had no significant effect on BK channel mRNA and protein levels and bioactivity. However, the dual inhibitor of mTORC1 and mTORC2 AZD8055 and short hairpin RNA targeting Rictor downregulated BK channel mRNA and protein levels and bioactivity. In addition, MK2206, GF109203X, and GSK650394, which are inhibitors of Akt, PKCα, and SGK1, respectively, were employed to test the downstream signaling pathway of mTORC2. MK2206 and GF109203X had no effect on BK channel protein levels. MK2206 caused an obvious decrease in the current density of the BK channels. Moreover, GSK650394 downregulated the BK channel protein and mRNA levels. These results indicate mTORC2 not only regulates the distribution of BK channels through Akt, but also modulates BK channel protein expression via SGK1 in podocytes.

Objective: To evaluate the diaphragm movement index of mechanical ventilation weaning patients by ultrosonography, and to explore its value for weaning., Methods: Forty patients undergoing invasive mechanical ventilation for at least 48 hours admitted to emergency intensive care unit (EICU) of Hunan Provincial People's Hospital from September 2017 to February 2018 were enrolled. Low level pressure support ventilation (PSV) was used for spontaneous breathing test (SBT), and bedside M-mode ultrasonography was used to assess the diaphragm movement index of the patient within 1 hour of SBT, including the excursion of the diaphragm, diaphragmatic-rapid shallow breathing index (D-RSBI). The rapid shallow breathing index (RSBI) was measured by ventilator. The patients who met the clinical weaning criteria were weaned. According to the success or failure of the weaning, the patients were divided into the successful weaning group and the failure weaning group. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of each indicator to the failure of the weaning., Results: A total of 40 patients were enrolled in the final analysis, including 28 patients in the successful weaning group and 12 patients in the failure weaning group. The excursion of the diaphragm in the failure weaning group was significantly less than that in the successful weaning group (mm: 9.56±2.13 vs. 13.66±4.10, P < 0.01), and the D-RSBI and RSBI were significantly higher than those in the successful weaning group [D-RSBI (times×min -1 ×mm -1 ): 2.06±0.68 vs. 1.44±0.66, RSBI (times×min -1 ×L -1 ): 61.70±25.00 vs. 44.91±14.51, both P < 0.05]. The area under the ROC curve (AUC) of diaphragm displacement, D-RSBI, and RSBI was 0.830, 0.851 and 0.711, respectively, and the predicted value of diaphragm excursion and D-RSBI was higher. When the optimal critical value of diaphragmatic excursion was 11.15 mm, the sensitivity of predicting weaning failure was 83.3%, the specificity was 71.4%; when the optimal critical value of D-RSBI was 1.42 times×min -1 ×mm -1 , the sensitivity of predicting the failure of weaning was 91.7%, and the specificity was 82.1%., Conclusions: Diaphragm excursion and D-RSBI of the diaphragmatic ultrosonography index could accurately predict the failure of the weaning, which was superior to the traditional RSBI in guiding weaning.

Objective: To investigate the clinical effect of pulmonary rehabilitation therapy including respiratory exercise and vibration expectoration on patients with pulmonary infection after abdominal surgery., Methods: A retrospective case control study was conducted. Seventy-six patients with pulmonary infection after abdominal surgery admitted to the First Affiliated Hospital of Hunan Normal University from September 2015 to September 2016 were enrolled. According to whether accept the pulmonary rehabilitation therapy or not, the patients were divided into two groups. In the control group (n = 35), the conventional expectoration method was adopted. The patients in pulmonary rehabilitation group (n = 41) received both methods of the control group and pulmonary rehabilitation treatment, including respiratory exercise (effective cough, lip reduction breathing), respiratory exercise device (respiratory exerciser tri-ball), and vibrated expectoration. The 24-hour sputum volume, degree of comfort, inflammatory and pulmonary function parameters, and recovery situation were recorded in the two groups., Results: (1) There were no significant differences in the parameters of inflammation and pulmonary function before treatment between the two groups. After treatment, the white blood cell (WBC) and C-reactive protein (CRP) in both groups were significantly decreased, and the forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) were significantly increased. The above changes in pulmonary rehabilitation group were more significant than those of the control group [WBC (×10 9 /L): 11.12±2.88 vs. 13.42±2.62 at 3 days, 8.22±1.48 vs. 9.27±1.92 at 5 days; CRP (mg/L): 13.47±4.77 vs. 16.03±4.94 at 3 days, 9.69±1.56 vs. 11.77±1.41 at 5 days; FEV1 (L): 2.48±0.14 vs. 2.29±0.16 at 3 days, FEV1/FVC: 0.78±0.04 vs. 0.75±0.04 at 3 days; all P < 0.05]. (2) The 24-hour sputum volume within 3 days of pulmonary rehabilitation group were significantly higher than that of the control group (mL: 30.51±4.15 vs. 18.30±3.64 at 1 day, 31.08±3.22 vs. 20.37±3.20 at 2 days, 29.03±2.55 vs. 19.03±2.51 at 3 days, all P < 0.01]. (3) In the pulmonary rehabilitation group, the recovery time of pulmonary infection symptoms (days: 5.44±1.45 vs. 6.20±1.55), the days of antibiotic use (days: 12.61±3.15 vs. 15.03±3.78), the time of getting out of the bed (days: 4.05±0.74 vs. 4.51±0.89), and the hospital days (days: 19.95±3.90 vs. 22.00±4.42) were significantly shorter than those of the control group (all P < 0.05), and the degree of comfort was significantly better than that of the control group (comfort score: 2.71±0.90 vs. 2.14±0.91, P < 0.01)., Conclusions: The application of pulmonary rehabilitation including respiratory exercise and vibration expectoration in abdominal surgery patients with pulmonary infection can promote recovery, and it has a good clinical and practical application value.