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

In the current process of talent cultivation in biology majors,some challenges like teaching content that lags behind the forefront of scientific research,instructional models that deviate from the principles of effective knowledge transmission,and evaluation systems that lack dimensions reflecting scientific innovation.As a strategy of tackling challenges,the Genetic Engineering teaching team,drawing on theoretical analysis and extensive teaching practice,has explored a reform of the instructional model from the perspective of integrating theory with practice.This effort led to the development of a research-oriented teaching model characterized by four iterative stages:knowledge instruction,thinking exercises,practical operation,and feedback evaluation.This model is ground-ed in five core elements of scientific thinking:criticality,coherence,simplicity,logic,and integrity.Imple-mentation follows the four-step framework,emphasizing structured knowledge delivery,cultivation of analytical thinking,hands-on experimentation,and comprehensive feedback.After one semester of application,it was found that through reconstructed knowledge systems,immersive simulations of research contexts,realistic problem-solving of technical bottlenecks and all-round feedback,this teaching model effectively fosters scientific thinking among both instructors and students,significantly enhances students'scientific research ca-pabilities and improves overall teaching effectiveness.

By extracting quantitative radiomic features from regions of interest in medical images and correlating them with the biological features and heterogeneity of tumors, radiomics can provide critical information and a basis for personalized precision diagnosis and treatment. Peritumoral regions contain a wealth of microbiological information. Therefore, chest CT peritumoral radiomics, which can provide quantitative non-invasive assessment for patients with non-small cell lung cancer (NSCLC) by mining the deep heterogeneity of peritumoral regions, has broad prospects for future clinical applications. Given the rapid progress in computer and medical big data techniques, as well as the in-depth efforts in multi-center, high-quality, and large-sample data in the future, it is reasonably believed that radiomics research will be gradually normalized and reproducible. This is conducive to the translation and application of radiomics research to clinical practice, thus laying a foundation for personalized and accurate diagnosis, treatment, and follow-up for lung cancer patients.

Mechanical ventilation (MV) is a powerful mean to rescue patients with respiratory failure. In view of the different etiology and basic respiratory function of patients with respiratory failure, weaning failure often occurs. Prolonged MV time is often accompanied by many complications. Thus, deeply understanding the pathophysiological changes of respiratory failure and strengthen monitoring of respiratory mechanics are helpful to optimize MV parameter settings, reduce ventilator-induced lung injury and wean from MV as early as possible. A successful weaning from MV depends on many factors, the most important factors are respiratory muscle strength, respiratory load and respiratory drive. Spontaneous breathing trial (SBT) is an important part of weaning process. The main purpose of implementing SBT is to screen patients and opportunities to weaning from MV, and find reversible reasons for not passing SBT. Because the accuracy of SBT in assessing weaning prognosis is about 85%, it is not adequate for difficult weaning patients. Standardized measurement of weaning indicators for patients with difficulty weaning is conducive to accurate assessment of respiratory muscle strength and improve the success rate of weaning from MV.

Prone position and position ventilation(PPV)are effective methods to save patients with refractory hypoxemia,and prone position has become the standard treatment for acute respiratory distress syndrome(ARDS).Successful clinical implementation requires understanding the mechanisms improving oxygenation and hemodynamic effects.In the use of prone position combined with PPV,the common factors affecting ventilation or oxygenation should be given extra an attention,such as the changes in respiratory mechanics,intra-abdominal pressure(IAP)and hemodynamics.However,consensus is lacking on optimal proning protocols and patient selection criteria.The causes of acute hypoxia and respiratory failure are complex,and should be assessed accurately.The success rate of rescuing critically ill patients can be improved by applying multiple effective treatments and standardized implementing prone position and PPV to improve oxygenation at the same time.

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

Volume dynamics is a two-compartment dynamical model using hemoglobin (Hb) derived plasma diluted level as input data and urine output as input variable through consecutive repeated measurements of Hb concentration in the blood during infusion. It could be applied to evaluate and guide crystalloid fluid rehydration for patients with dehydration or hypovolemia and during anesthesia or surgery. Volume dynamics could be also used to quantificate of strains, hypovolume, and the change of fluid distribution and elimination caused by anesthesia or surgery. The factors which influence the volume resuscitation are complex, including gender, age, hemodynamic state [mean arterial pressure (MAP)], health and stress state, renal function, consciousness, surgical or anesthesia state and so on, which may affect the half-life, distribution, and volume of the fluid. This article summarizes and analyzes the pathophysiological changes of crystalloids fluid in vivo, in order to provide reference for volume management in critically ill patients.

Objective:To analyze the possible causes of arrhythmia in patients receiving continuous renal replacement therapy (CRRT) with regional citrate anticoagulation (RCA).Methods:A retrospective cohort study was conducted. All patients underwent RCA-CRRT treatment from January 1, 2020 to October 31, 2020 in the intensive care unit (ICU) of Tianjin Third Central Hospital were enrolled. The patients were divided into arrhythmia group and non-arrhythmia group according to whether arrhythmia occurred. The gender, age, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, catheterization site, underlying diseases, electrocardiogram (ECG), electrolytes [total calcium, serum free calcium (iCa 2+), phosphorus, magnesium, potassium] and blood gas analysis (pH value, HCO 3-) of patients in the two groups were recorded. The changes of ECG were observed, the differences in electrolyte and blood gas analysis indexes between the two groups of patients at different time points (before CRRT, 24, 48, 72 hours after CRRT, and when arrhythmia occurred) were compared. Results:A total of 86 RCA-CRRT patients were enrolled, of which 12 cases (13.95%) had arrhythmia, and the remaining 74 cases (86.05%) had no arrhythmia. The average time for the occurrence of arrhythmia in the 12 patients was (44.00±16.82) hours. There was no significant ST-segment change in the ECG when the arrhythmia occurred compared with that before CRRT, the total calcium level was significantly higher than that before CRRT (mmol/L: 2.48±0.40 vs. 2.13±0.35, P < 0.05), the blood magnesium level was significantly lower than that before CRRT (mmol/L: 0.73±0.20 vs. 0.95±0.25, P < 0.05). There was no significant difference in iCa 2+, blood phosphorus, blood potassium, pH value and HCO 3- between before CRRT and when arrhythmia occurred. Over time, the total calcium levels in the two groups increased, and there was a statistical difference between the 48 hours after CRRT and before CRRT (mmol/L: 2.48±0.33 vs. 2.13±0.35 in the arrhythmia group, and 2.30±0.22 vs. 2.15±0.48 in non-arrhythmia group, both P < 0.05). The linear change trend of iCa 2+, pH value and HCO 3- was not obvious in the two groups. The blood phosphorus and blood magnesium levels in the two groups decreased. The blood potassium in the arrhythmia group decreased, however, the blood potassium level in non-arrhythmia group did not change significantly. The total calcium level in the arrhythmia group was significantly higher than that in the non-arrhythmia group at 72 hours after CRRT (mmol/L: 2.69±0.35 vs. 2.45±0.23, P < 0.05); however, there was no significant difference in serum iCa 2+, phosphorus, magnesium, potassium, pH value and HCO 3- between the two groups. Conclusion:Patients receiving RCA-CRRT were less likely to develop arrhythmia, the causes may be related to the accumulation of citric acid and electrolyte disturbances such as calcium, phosphorus, and magnesium.

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.