OBJECTIVE: To investigate the mechanism of autophagy in regulating bacterial translocation in intestinal infection caused by hypervirulent Klebsiella pneumonia (hvKp) and explore the method of reducing translocation infection of intestinal bacteria. METHODS: Fifty C57BL/6J mice were divided into gavage group (n = 40) and control group (CO group, n = 10). The gavage group was orally administered with 200 μL/d of hvKp (colony count of 10⁹ CFU/mL) continuously for 5 days to establish a hvKp intestinal infection model. CO group was given an equal amount of normal saline. After the experiment, the mice were anesthetized with lsofluraneand euthanized with cervical dislocation under anesthesia. Peripheral venous blood of mice was collected to detect bacterial translocation by 16S rDNA sequencing, then divided into translocation group (BT+ group) and non-translocation group (BT- group). Hematoxylin-eosin (HE) staining was used to evaluate intestinal morphology. The ultrastructural changes of intestinal tissues were observed by electron microscope. The levels of intestinal oxidative stress indicators such as superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GPx) were measured. Translocation was detected by in situ hybridization. The expression of tight junction protein microtubule-associated protein 1 light chain 3-II (LC3-II) and autophagy protein Beclin-1 were measured by Western blotting. The mRNA expression of tight junction proteins ZO-1 and Claudin-2 were detected by reverse transcription-polymerase chain reaction (RT-PCR). The expression of autophagy protein and tight junction protein were observed by immunofluorescence. RESULTS: Two out of 40 mice in the gavage group died after developing aspiration pneumonia. All mice in the CO group survived. The 16S rDNA sequencing results showed that no bacteria were detected in the peripheral blood of the CO group, but bacteria were detected in the peripheral blood of 18 mice in the gavage group, with a bacterial translocation rate of 47.4%. The BT- and BT+ groups showed intestinal mucosal tissue damage, with severe damage in the BT+ group. Compared with the CO group, the level of MDA in the BT- and BT+ groups were significantly increased, while the activities of SOD and GPx were significantly decreased. Compared with the BT- group, the MDA level in the BT+ group further increased, while the SOD and GPx activities further decreased [MDA (mmol/mg): 2.98±0.11 vs. 2.48±0.11, SOD (U/mg): 62.40±5.45 vs. 73.40±4.08, GPx (U/mg): 254.72±10.80 vs. 303.55±8.57, all P < 0.01]. The results of in situ hybridization detection showed that after continuous gastric lavage for 5 days, displaced hvKp was detected in the intestinal mucosal lamina propria and liver tissue of the BT+ group. Compared with the CO group, the protein expressions of LC3-II and Beclin-1 in the BT- and BT+ groups were significantly increased. The protein expressions of LC3-II and Beclin-1 in the BT+ group were obviously lower than those in the BT- group (LC3-II/β-actin: 0.38±0.04 vs. 0.70±0.09, Beclin-1/β-actin: 0.62±0.05 vs. 0.86±0.05, both P < 0.01), and there were autophagosomes in the intestinal mucosa. These results indicated that intestinal mucosal autophagy was activated after hvKp continuous gavage. Compared with CO group, the mRNA expressions of ZO-1 and Claudin-2 in the BT- and BT+ groups were significantly decreased. Compared with the BT- group, the mRNA expressions of ZO-1 and Claudin-2 in the BT+ group was further reduced [ZO-1 mRNA (2^-ΔΔCT): 0.78±0.06 vs. 0.88±0.06, Claudin-2 mRNA (2^-ΔΔCT): 0.40±0.04 vs. 0.70±0.06, both P < 0.01]. The immunofluorescence results showed that the fluorescence intensity of LC3-II, Beclin-1, ZO-1, and Claudin-2 in the BT+ group was significantly lower than that in the BT- group. CONCLUSION HvKp can activate intestinal mucosal autophagy and reduce the damage to intestinal mucosal barrier function by down-regulating oxidative stress level, reduce the occurrence of bacterial translocation.
Animals ; Oxidative Stress ; Mice, Inbred C57BL ; Autophagy ; Intestinal Mucosa/microbiology* ; Bacterial Translocation ; Mice ; Klebsiella Infections/microbiology* ; Superoxide Dismutase/metabolism* ; Beclin-1

OBJECTIVE: To investigate the value of maximal rate of left ventricular pressure (dp/dtmax) in evaluating the changes of cardiac function before and after heart rate reduction in patients with sepsis-induced cardiomyopathy (SIC). METHODS: A single-center, prospective randomized controlled study was conducted. Adult patients with sepsis/septic shock admitted to the department of intensive care unit (ICU) of Tianjin Third Central Hospital from April 1, 2020 to February 28, 2022 were enrolled. Speckle tracking echocardiography (STE) and pulse indication continuous cardiac output (PiCCO) monitoring were performed immediately after the completion of the 1 h-Bundle therapy. The patients with heart rate over 100 beats/minutes were selected and randomly divided into esmolol group and regular treatment group, 55 cases in each group. All patients underwent STE and PiCCO monitoring at 6, 24 and 48 hours after admission in ICU and calculated acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA). Primary outcome measure: change in dp/dtmax after reducing heart rate by esmolol. Secondary outcome measures: correlation between dp/dtmax and global longitudinal strain (GLS); changes of vasoactive drug dosage, oxygen delivery (DO₂), oxygen consumption (VO₂) and stroke volume (SV) after the administration of esmolol; proportion of heart rate reaching the target after the administration of esmolol; 28-day and 90-day mortality in two groups. RESULTS: Baseline data on age, gender, body mass index, SOFA score, APACHE II score, heart rate, mean arterial pressure, lactic acid, 24-hour fluid balance, sepsis etiology and prior comorbidities were similar between esmolol group and regular treatment group, there were no significant differences between the two groups. All SIC patients achieved the target heart rate after 24 hours of esmolol treatment. Compared with regular treatment group, parameters reflecting myocardial contraction such as GLS, global ejection fraction (GEF) and dp/dtmax were significantly increased in esmolol group [GLS: (-12.55±4.61)% vs. (-10.73±4.82)%, GEF: (27.33±4.62)% vs. (24.18±5.35)%, dp/dtmax (mmHg/s): 1 312.1±312.4 vs. 1 140.9±301.0, all P < 0.05], and N-terminal pro-brain natriuretic peptide (NT-proBNP) significantly decreased [μg/L: 1 364.52 (754.18, 2 389.17) vs. 3 508.85 (1 433.21, 6 988.12), P < 0.05], DO₂ and SV were significantly increased [DO₂ (mL×min^-1×m^-2): 647.69±100.89 vs. 610.31±78.56, SV (mL): 49.97±14.71 vs. 42.79±15.77, both P < 0.05]. The system vascular resistance index (SVRI) in esmolol group was significantly higher than that in regular treatment group (kPa×s×L^-1: 287.71±66.32 vs. 251.17±78.21, P < 0.05), even when the dosage of norepinephrine was similar between the two groups. Pearson correlation analysis showed that dp/dtmax was negatively correlated with GLS in SIC patients at 24 hours and 48 hours after ICU admission (r values were -0.916 and -0.935, respectively, both P < 0.05). Although there was no significant difference in 28-day mortality between esmolol group and regular treatment group [30.9% (17/55) vs. 49.1% (27/55), χ² = 3.788, P = 0.052], the rate of esmolol use in patients who died within 28 days was lower than that in patients who survived [38.6% (17/44) vs. 57.6% (38/66), χ² = 3.788, P = 0.040]. In addition, esmolol has no effect on the 90-day mortality of patients. Logistic regression analysis showed that after adjusting for SOFA score and DO₂ factors, patients who used esmolol had a significantly lower risk of 28-day mortality compared with patients who did not use esmolol [odds ratio (OR) = 2.700, 95% confidence interval (95%CI) was 1.038-7.023, P = 0.042]. CONCLUSIONS dp/dtmax in PiCCO parameter can be used as a bedside indicator to evaluate cardiac function in SIC patients due to its simplicity and ease of operation. Esmolol control of heart rate in SIC patients can improve cardiac function and reduce short-term mortality.
Adult ; Humans ; Prospective Studies ; Ventricular Pressure ; Sepsis/complications* ; Shock, Septic/drug therapy* ; Cardiomyopathies/etiology* ; Prognosis

Objective:To investigate the clinical effect of setting proportional pressure support (PPS) parameters by target tidal volume (VT) method.Methods:The study was conducted retrospectively on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients admitted to Tianjin Third Central Hospital from January 2016 to December 2020. According to the PPS parameter setting method, the patients were divided into the airway blocking group and target VT group. The baseline characteristics, initial setting values of flow assist (FA) and volume assist (VA), respiratory system parameters, and clinical outcomes were collected and compared between the two groups.Results:Fifty-nine patients were enrolled, 29 patients in the airway blocking group, and 30 in the target VT group. There was no statistically significant difference in baseline characteristics, compliance, resistance, and initial settings of FA and VA between the two groups. Compared with the target VT group, the respiratory rate (RR), mean arterial pressure (MAP), VT, and arterial partial pressure of oxygen (PaO 2) recorded 1 hour after the initial setting of the PPS parameters in the airway block method group were significantly reduced [RR (times/minute): 21.0 (18.5, 22.5) vs. 23.0 (21.0, 25.0), MAP (mmHg, 1 mmHg = 0.133 kPa): 84.0 (79.0, 90.5) vs. 90.0 (87.0, 96.2), VT (mL): 305.24±41.07 vs. 330.87±46.84, PaO 2 (mmHg): 68.0 (66.0, 73.5) vs. 74.0 (69.8, 82.5), all P < 0.05], while arterial partial pressure of carbon dioxide (PaCO 2) and oral closure pressure (P0.1) were both increased significantly [PaCO 2 (mmHg): 41.0 (39.0, 46.0) vs. 37.5 (35.0, 42.2), P0.1 (cmH 2O, 1 cmH 2O = 0.098 kPa): 1.42±0.78 vs. 0.90±0.67, both P < 0.05]. Compared with airway blocking group, the duration of weaning, ICU stay, and hospital stay in the target VT group were significantly shorter [duration of weaning (hours): 42.0 (24.0, 70.5) vs. 64.0 (30.5, 97.5), ICU stay: 10.00±3.38 to 13.28±5.41, hospital stay (days): 12.07±3.40 vs. 15.41±5.60, all P < 0.05]. There was no statistically significant difference in the invasive mechanical ventilation time, weaning failure rate, ICU mortality and in-hospital mortality between the two groups. Conclusion:This study suggested that the target TV method has the advantages of practicality, safety, convenience, and rapid to set PPS parameters than the airway block method, which shortens the duration of weaning and ICU stay, and has a good clinical prospect.

Objective:To establish a model that can predict weaning failure from ventilation through hemodynamic and fluid balance parameters.Methods:A retrospective analysis was conducted. The patients who underwent invasive mechanical ventilation for more than 24 hours and having spontaneous breathing test admitted to intensive care unit (ICU) of Tianjin Third Central Hospital from January 1st, 2017 to December 31st, 2018 were enrolled. The information was collected, which included the baseline data, hemodynamic parameters by pulse indicator continuous cardiac output (PiCCO) monitoring, B-type natriuretic peptide (BNP), urinary output, fluid balance in first 24 hours when patients admitted to ICU, and hemodynamic parameters by PiCCO monitoring, BNP, urinary output, fluid balance, diuretic usage, noradrenalin usage within 24 hours before weaning as well as usage of continuous renal replacement therapy (CRRT) during mechanical ventilation. According to weaning success or failure, the patients were divided into weaning success group and weaning failure group, and the statistical differences between the two groups were calculated. Variables with statistical significance within 24 hours before weaning were included in the multivariate Logistic regression analysis to establish weaning failure prediction model and find out the possible risk factors of weaning failure.Results:A total of 159 patients were included in this study, which included 138 patients in the weaning success group and 21 patients in the weaning failure group. There were no statistical differences in all hemodynamic parameters by PiCCO monitoring, BNP, urinary output, fluid balance within 24 hours into ICU between two groups. There were statistical differences in BNP ( χ2 = 9.262, P = 0.026), central venous pressure (CVP; χ2 = 7.948, P = 0.047), maximum rate of the increase in pressure (dPmx; χ2 = 10.486, P = 0.015), urinary output ( χ2 = 8.921, P = 0.030), fluid balance ( χ2 = 9.172, P = 0.027) within 24 hours before weaning between two groups. In addition, variable about cardiac index (CI; χ2 = 7.789, P = 0.051) was included into multivariate Logistic regression model to improve the prediction model and enhance the accuracy of model. Finally, variables included in the multivariate Logistic regression model were BNP, CVP, CI, dPmx, urinary output, fluid balance volume, and the accuracy of the weaning failure prediction model was 92.9%, the sensitivity was 100%, and the specificity was 76.8%. When the model was adjusted by variables of age and noradrenalin usage, the accuracy of model to predict failure of weaning was 94.2%, the sensitivity was 100%, the specificity was 81.2%. Conclusion:Weaning failure prediction model based on hemodynamic parameters by PiCCO monitoring and variables about liquid balance has high accuracy and can guide clinical weaning.

Objective To investigate the occurrence and influencing factors of long-term cognitive impairment in patients with sepsis. Methods The septic patients admitted to intensive care unit (ICU) of Tianjin Third Central Hospital from July 2014 to September 2017 were enrolled. Montreal cognitive assessment scale (MoCA) was used to assess the cognitive function of patients at 3, 12 and 24 months after discharge from hospital. The patients were divided into cognitive impairment group (MoCA score < 26) and normal cognitive function group (MoCA score ≥ 26) according to the MoCA scores at 12 months after discharge from hospital. The basic characteristics and clinical data were recorded in both groups, the variables with statistical significance in univariate analysis were enrolled in bivariate Logistic regression analysis, and the influencing factors of cognitive impairment in patients with sepsis were screened. Results During the study period, 1 748 patients with sepsis were admitted, 210 survived and discharged, and 125 patients participated in the follow-up. Cognitive impairment occurred in 61.6% (77/125), 54.4% (56/103) and 54.2% (39/72) of the septic patients at 3, 12 and 24 months after discharge, respectively. The MoCA score of 103 patients who completed 12-month follow-up was significantly higher than that of 3-month follow-up (23.4±5.7 vs. 23.0±6.0, P < 0.01); the MoCA score of 72 patients who completed 24-month follow-up was only slightly lower than that of 12-month follow-up (23.6±5.4 vs. 23.7±5.0, P > 0.05). Following up for 12 months, 47 patients were enrolled in the normal cognitive function group and 56 in the cognitive impairment group. Compared with the normal cognitive function group, the cognitive dysfunction group had more female [51.8% (29/56) vs. 31.9% (15/47)] and older patients (years old: 66.1±15.9 vs. 52.4±18.9), also had shorter time to receive education (years: 7.6±4.0 vs. 11.2±3.1), longer duration of delirium [days: 2 (0, 3) vs. 0 (0, 1)], with significant differences (all P < 0.05). There was no significant difference in the marital status, severity of infection, underlying diseases, routes of transfer, total length of hospital stay, the length of ICU stay, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score, sequential organ failure assessment (SOFA) score, Charlson comorbidity index (CCI) score within 24 hours of admission to ICU, hypoxemia, hypotension, mechanical ventilation, hemofiltration, or drug use between the two groups. Bivariate Logistic regression analysis showed that the duration of education was a protective factor for cognitive impairment in patients with sepsis who were followed up for 12 months [odds ratio (OR) = 0.791, 95% confidence interval (95%CI) = 0.678-0.923, P = 0.003], and age and duration of delirium were risk factors (age: OR = 1.038, 95%CI = 1.009-1.068, P = 0.010; duration of delirium: OR = 1.314, 95%CI = 1.002-1.724, P = 0.048). Conclusions Long-term cognitive impairment occurs in many septic patients after discharge and improves over time. Duration of education is a protective factor for cognitive impairment in patients with sepsis, while age and delirium duration are risk factors.

Objective To investigate the effect of different appropriate modes of weaning from mechanical ventilation (MV) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods Patients with AECOPD and mechanically ventilated by orotracheal intubation, suitable for continuous positive airway pressure+proportional pressure support (CPAP+PPS) and CPAP+assisted spontaneous breath (ASB) ventilation mode for weaning from MV, admitted to intensive care unit (ICU) of Tianjin Third Central Hospital form January 1st, 2016 to December 31st, 2017 were enrolled. When the patients recovered to spontaneous respiration and down regulation of ventilator support frequency to 10 bpm, they were taken ventilator weaning in CPAP+PPS and CPAP+ASB mode according to the random number table method, respectively. Basic characteristics, ventilator parameters, the incidence of high man-machine confrontation (man-machine confrontation index > 10%) and clinical outcomes (ventilator weaning time, which was defined as the time from randomization to successful weaning from MV, ventilator weaning failure times, the duration of MV, the length of ICU stay and the length of hospital stay) were compared between the two groups. Results Eighty-seven AECOPD patients were selected, 44 in CPAP+ASB group and 43 in CPAP+PPS group. There was no significant difference in gender, age, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ), sequential organ failure score (SOFA), Glasgow coma score (GCS), Charsen index and the highest arterial blood carbon dioxide partial pressure (PaCO2), the lowest arterial oxygen partial pressure (PaO2) and tidal volume (VT) at the time of onset between the two groups. Compared with CPAP+ASB group, incidence of high man-machine confrontation was significantly decreased in CPAP+PPS group [9.30% (4/43) vs. 27.27% (12/44), P =0.027], and the airway occlusion pressure (P0.1) was significantly decreased [cmH2O (1 cmH2O = 0.098 kPa): 2.21±0.83 vs. 2.63±0.94, P = 0.032], and the failure rate of the first spontaneous breathing trial (SBT) was significantly decreased [6.98% (3/43) vs. 22.73% (10/44), P = 0.039], ventilator weaning time, the length of ICU stay and the length of hospital stay were significantly shortened [ventilator weaning time (hours): 12.73±14.23 vs. 50.64±38.11, the length of ICU stay (hours): 254.53±108.06 vs. 344.93±124.95, the length of hospital stay (days): 18.53±7.59 vs. 26.64±11.22, all P < 0.05]. However, there was no significant difference in PaCO2, duration of MV, ICU mortality and hospital mortality between the two groups. Conclusion Compared with CPAP+ASB ventilation mode, CPAP+PPS ventilation mode can reduce respiratory muscle load, promote respiratory function recovery, and reduce the occurrence of man-machine confrontation, which is beneficial to AECOPD patients taking ventilator weaning, and can significantly shorten the ventilator weaning time of patients and further shorten the hospitalization time.

Objective To investigate the predictive value of continuous dynamic monitoring of intrapulmonary shunt (Qs/Qt) in patients with acute respiratory distress syndrome (ARDS).Methods A prospective observational study was conducted.The adult patients with ARDS undergoing mechanical ventilation admitted to intensive care unit (ICU) of Tianjin Third Central Hospital from June 2014 to December 2015 were enrolled.Baseline characteristics,demographic data and relevant physiologic data were recorded.All patients were divided into survivors and non-survivors according to the outcome of patients within 28 days.Artery and mixed venous blood was collected immediately after admission for blood gas analysis,and daily Qs/Qt within 7 days was continuously monitored in ARDS patients.The receiver operating characteristic curve (ROC) was used to evaluate the prognosis accuracy of Qs/Qt.Results In 46 enrolled ARDS patients,20 died,and 26 survived.During the first 7 days of ARDS,the mean Qs/Qt in survivors showed an increasing tendency [(23 ± 6)％,(27 ± 6)％,(28 ± 9)％,respectively,at 1-3 days] and a downtrend tendency from 4 days [(27 ± 5)％,(25 ± 4)％,(19 ± 4)％,(16 ± 2)％,respectively,at 4-7 days].However,a rising tendency of Qs/Qt in non-survivors was found at 1-7 days [(28 ± 7)％,(30 ± 3)％,(33 ± 6)％,(33 ± 11)％,(34 ± 5)％,(33 ± 6)％,(35 ± 6)％,respectively],and Qs/Qt from the 5th day in non-survivors was significantly higher than that in survivors (all P ＜ 0.05).The fluctuation of oxygenation index (PaO2/FiO2) within 1 week in both groups was small,and PaO2/FiO2 (mmHg,1 mmHg =0.133 kPa) at 1-7 days in survivors was 167.37±43.98,180.55±39.90,174.27±35.47,188.64±39.74,252.54±49.22,239.35±25.63,248.93±45.64,respectively,and it was 168.65±35.54,182.31 ± 32.36,159.80 ± 34.39,176.97 ± 31.75,200.69 ± 45.33,185.98 ± 36.47,and 175.43 ± 30.98 in non-survivors respectively.PaO2/FiO2 was significantly lower in non-survivors than survivors from 5 days (all P ＜ 0.05).It was shown by ROC curve that area under ROC curve (AUC) for Qs/Qt evaluating the prognosis on the 5th day was 0.958,and 95％ confidence interval (95％CI) was 0.777-0.999 (P ＜ 0.000 1,Z =13.13).When the cut-off value of Qs/Qt was 28％,sensitivity and specificity were 83.3％ and 90.0％,respectively.AUC for PaO2/FiO2 evaluating the prognosis on the 5th day was 0.790,and 95％CI was 0.577-0.928 (P =0.002 1,Z =3.08).When the cut-off value of PaO2/FiO2 was 223 mmHg,sensitivity and specificity were 69.2％ and 81.8％,respectively.Conclusion Dynamic Qs/Qt surveillance can help physician to analyze the changes of the patient's condition,and it was better than PaO2/FiO2,and can be an important evaluation indicator of prognosis for ARDS patients.

ObjectiveTo assess the clinical value of procalcitonin (PCT) in the diagnosis of sepsis in adults.Methods An extensive search for related literature from the Wanfang data, CNKI, VIP, Medline/PubMed, Embase/OvidSP and the Cochrane Library up to December 2014 was performed. The articles, including prospective observational studies or randomized controlled trials, regarding PCT for the diagnosing of sepsis were enrolled. Only patients older than 18 years were included. Patients with sepsis, severe sepsis, or septic shock served as the experimental group, and those with a systemic inflammatory response syndrome (SIRS) of non-infectious origin as control group. The language of literature included was English or Chinese. The quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Heterogeneity, pooled diagnostic odds ratio (DOR), pooled sensitivity, pooled specificity, pooled positive likelihood ratio, pooled negative likelihood ratio, the area under the summary receiver operating characteristic curve (SROC) and subgroup analysis were analyzed with the software of Metadisc 1.4.Results A total of 6 385 published reports were collected, and among them 24 met the inclusion criteria, including a total of 3 107 patients. The studies showed substantial heterogeneity (I2 = 69.4%), and random effect model was used for Meta analysis, showing that the pooledDOR was 10.37 [95% confidence interval (95%CI) = 7.10-15.17]. No evidence of a threshold effect was found (Spearman correlation coefficient = 0.27, calculated by logarithm of sensitivity and logarithm of 1-specificity,P = 0.20). TheDOR values of pooled and each study were not distributed along the same line in forest plots, and Cochran-Q = 78.33,P = 0.000 0, showing that there was heterogeneity in result from non threshold effect. Except for partial heterogeneity caused by non threshold effect, the result of Meta regression analysis including PCT detection method, categories of disease, research location and so on showedP values were all higher than 0.05. Thus, the heterogeneity could not be explained by Meta regression analysis. The pooled sensitivity was 74% (95%CI = 72%-76%), the pooled specificity was 70% (95%CI = 67%-72%), the pooled positive likelihood ratio was 2.79 (95%CI = 2.31-3.38), the pooled negative likelihood ratio was 0.34 (95%CI = 0.28-0.41), and the pooled AUC was 0.83 (95%CI = 0.79-0.87). AUC in medical patients was 0.80 (95%CI = 0.75-0.85), which was higher than that in surgical patients [0.71 (95%CI = 0.65-0.81)].Conclusions Our results indicate a moderate degree of value of PCT for diagnosis of sepsis in adult patients. The diagnostic accuracy in medical patients is higher than that in surgical patients. PCT is a good auxiliary biomarker for diagnosis of sepsis.