Health Care Working Committee of Chinese Rehabilitation Medical Association, Hyperbaric Oxygen Rehabilitation Professional Committee of Chinese Rehabilitation Medical Association, Chinese Enterprise Management Research Association-Public Health and Medical Health Management Think Tank
To investigate the impact of the stimulator of interferon genes (STING) on the repair process of acute lung injury in mice and its influence on macrophages efferocytosis.
Methods
Twenty-five C57BL/6 mice aged 10-12 weeks were randomly divided into a D0 group, a D1 group, a D3 group, a D5 group and a D7 group, with five mice in each group, and the mice samples were collected after 0, 1, 3, 5 and 7 days of an intratracheal injection of 0.5 mg/kg lipopolysaccharide (LPS) respectively. In addition, five STING wild-type (STING+/+) mice and five STING knockout (STING-/-) mice were selected and divided into a STING+/+ + LPS group and a STING-/- + LPS group, and the mice samples were collected after 5 days of an intratracheal injection of 0.5 mg/kg LPS. Hematoxylin eosin (HE) staining was employed to observe the pathological changes in lung tissue, and the cell count, neutrophil count and protein concentration in alveolar lavage fluid were detected to access the degree of lung injury. Apoptotic neutrophils were injected into the trachea of mice, and alveolar lavage fluid cells were collected 3 hours later for flow cytometry to determine the efferocytosis rate of macrophages. TUNEL and F4/80 double staining of lung tissues were conducted via immunofluorescence to evaluate efferocytosis. The phenomenon of macrophage efferocytosis was observed through Pap staining.
Results
The C57BL/6 mice reached the peak of lung injury 3 days after induction of acute lung injury and began to repair after 5 days, and in the absence of treatment, the repair was basically completed within 7 days. After 5 days of acute lung injury, the lung tissue injury score and the protein concentration, total cell count and neutrophil count in alveolar lavage fluid of mice in the STING-/- + LPS group were lower than those in the STING+/+ + LPS group (t = 3.257, 2.926, 3.946, 2.669; P = 0.012, 0.019, 0.004, 0.028). Flow cytometry and immunofluorescence staining showed that the efferocytosis rates of alveolar macrophages in the STING-/- + LPS group were significantly higher than those in the STING+/+ + LPS group (t = 3.143, 6.963; P = 0.016, < 0.001).
Conclusions
Deletion of STING may regulate the repair process of acute lung injury through enhancing macrophage efferocytosis. Therefore, this study provides new insights into the role of STING in the lung injury and repair.
To investigate the regulation of exogenous human telomerase reverse transcriptase (hTERT) expression by the exogenous interleukin-6 (IL-6) promoter and its effect on cell senescence.
Methods
The IL-6 promoter was fused with enhanced green fluorescent protein (EGFP) (GV3-IL-EGFP) or hTERT-EGFP (GV3-IL-hT-EGFP) to construct lentiviral vectors. The corresponding virus particles were collected and transfected into the fifth generation human foreskin fibroblasts-1 (HFF-1). The replicative cell senescence model was constructed by natural passage cells, and HFF-1 transfected with recombinant virus of GV3-IL-EGFP was used as the control group and HFF-1 transfected with recombinant virus of GV3-IL-hT-EGFP was used as the gene therapy group. The expression level of hTERT protein in cells of the two groups was detected when the cells were approaching complete senescence (19th and 25th generations), and the curve of cell population doubling level (PDL) was drawn. The expression levels of radiation sensitive protein 51 (RAD51) and gamma-H2A histone family member X (γ-H2AX) proteins were detected when the growth rates of cells in the two groups were different (13th, 14th and 15th generations). The expression levels of IL-6 and IL-1α proteins were detected at the 15th, 17th and 19th generations. At the same time, the protein expression levels of RAD51 and γ-H2AX were compared between the two groups after 100 nM doxorubicin treatment for 48 h in the 13th, 14th and 15th generations.
Results
The expression level of hTERT protein at the 19th generation in the control group and the 19th and 25th generations in the gene therapy group was significantly different (F = 941.781, P < 0.001). Compared with the 19th generation in the control group, the expression level of hTERT protein at the 19th and 25th generations in the gene therapy group were increased significantly (both P < 0.001). The protein expression levels of IL-6 (t = 61.570, P < 0.001; t = 36.527, P < 0.001) and IL-1α (t = 11.984, P < 0.001; t = 18.622, P < 0.001) at 17th and 19th generations in the gene therapy group were obviously down-regulated as compared with the control group. The expression levels of RAD51 and γ-H2AX proteins of the control group at the 14th generation (t = 3.101, P = 0.036; t = 10.226, P = 0.001) and at the 15th generation (t = 8.683, P = 0.001; t = 7.229, P = 0.002) were much higher than those of the gene therapy group. PDL curve showed that at the 19th generation, the cells in the control group stopped proliferating and were in a completely senescent state, while the cells in the gene therapy group still had proliferative ability (t = 6.856, P = 0.002). After doxorubicin treatment, the expression levels of RAD51 (t = 23.479, P < 0.001; t = 9.619, P = 0.001; t = 14.971, P < 0.001) and γ-H2AX (t = 4.275, P = 0.013; t = 6.787, P = 0.002; t = 9.569, P = 0.001) in the gene therapy group at the 13th, 14th and 15th generations were much lower than those in the control group.
Conclusion
During replicative cellular senescence and doxorubicin-induced cellular senescence, GV3-IL-hT-EGFP fibroblasts can reduce the accumulation of DNA damage and the levels of inflammatory factors by regulating the expression of hTERT after gene therapy.
Intestinal biomarkers of intestinal fatty acid binding protein (I-FABP), D-lactic acid, and citrulline were used to evaluate the advantages and disadvantages of three nutritional strategies in patients with severe gastrointestinal injury.
Methods
A total of 117 patients with severe gastrointestinal injury were selected from the Intensive Care Unit of the Affiliated Suzhou Hospital of Nanjing Medical University from February 2021 to January 2023. All enrolled patients were divided into a standard feeding group (38 cases), a nourishing enteral nutrition (EN) + parenteral nutrition (PN) group (40 cases), and a total parenteral nutrition (TPN) group (39 cases) by a random number table method. Early EN began 24 h after admission. The baseline data, gastrointestinal tolerance, 28-day survival rate, and levels of I-FABP, D-lactic acid and citrulline at different time points were compared among the three groups. The incidence of feeding interruption was compared between the standard feeding group and the nourishing EN + PN group. The duration of enteral feeding in the standard feeding group and the nourishing EN + PN group was recorded, and a Kaplan-Meier survival curve was drawn.
Results
There were significant differences in the levels of I-FABP, D-lactic acid, and citrulline before EN and on the 3rd and 7th days of admission among the three groups (F = 2.772, 2.797, 7.902; P = 0.028, 0.027, < 0.001). Further pair-to-pair comparison showed that the levels of I-FABP and D-lactic acid in the nourishing EN + PN group were significantly lower than those in the standard feeding group, while the level of I-FABP in the TPN group was significantly higher than that in the nourishing EN + PN group on the 3rd day of admission (all P < 0.05). The level of citrulline in the nourishing EN + PN group was significantly higher than that in the standard feeding group and the TPN group on the 7th day after admission (both P < 0.05). The incidence of vomiting/gastric retention was significantly different [50.0% (19/38) vs. 45.0% (18/40) vs. 23.1% (9/39), χ2 = 6.670, P = 0.036], while the incidence of abdominal distension [52.6% (20/38) vs. 45.0% (18/40) vs. 48.7% (19/39), χ2 = 0.454, P = 0.797] and diarrhea [23.7% (9/38) vs. 17.5% (7/40) vs. 17.9% (7/39), χ2 = 0.580, P = 0.748], and 28-day survival rate [55.3% (21/38) vs. 65.0% (26/40) vs. 61.5% (24/39), χ2 = 0.792, P = 0.673] were not statistically significantly different among the three groups. There was no significant difference in feeding interruption between the standard feeding group and the nourishing EN + PN group [60.5% (23/38) vs. 47.5% (19/40), χ2 = 1.331, P = 0.249]. The Kaplan-Meier survival curve showed that nourishing EN + PN could prolong EN feeding duration within seven days (χ2 = 3.996, P = 0.046).
Conclusion
Based on changes in intestinal biomarkers within seven days after admission, early nourishing EN + PN is more beneficial to the recovery of gastrointestinal function in patients with severe gastrointestinal impairment (acute gastrointestinal injury III) than standard feeding and TPN, and partially improves gastrointestinal tolerance.
To explore the predictive value of combined detection of platelet to lymphocyte ratio (PLR), procalcitonin (PCT) and interleukin-6 (IL-6) in 28-day prognosis of patients with sepsis.
Methods
The clinical data of 126 patients with sepsis admitted to the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from October 2021 to June 2023 were retrospectively analyzed. According to the clinical outcome of 28 days, they were divided into a survival group (95 patients) and a death group (31 patients). The indexes detected within 24 hours of treatment in the Department of Emergency Medicine were compared between the two groups, including the general information, PLR, PCT, IL-6, lactic acid, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE) II score, platelet count and lymphocyte count. Multivariate logistic regression analysis was used to detect the risk factors affecting the death of sepsis patients. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of PLR, PCT and IL-6 in the prognosis of sepsis patients.
Results
The PLR, PCT, IL-6, lactic acid, SOFA score and APACHEII score of the death group were higher than those of the survival group (all P < 0.05). Multivariate logistic regression analysis showed that the PLR [odds ratio (OR) = 1.018, 95% confidence interval (CI) (1.009, 1.028), P < 0.001], PCT [OR = 1.040, 95%CI (1.018, 1.064), P < 0.001], IL-6 [OR = 1.065, 95%CI (1.004, 1.109), P = 0.045] and APACHEII score [OR = 1.194, 95%CI (1.075, 1.325), P < 0.001] were independent risk factors for adverse outcomes in patients with sepsis. The ROC curve analysis showed that the combined use of PLR, PCT and IL-6 had better predictive value for the 28-day prognosis of sepsis patients than the use of PLR, PCT and IL-6 alone (Z = 2.059, 2.144, 2.001; P = 0.039, 0.032, 0.045).
Conclusion
The levels of PLR, PCT and IL-6 significantly increased in patients who died of sepsis, and they are independent risk factors for predicting the 28-day prognosis of sepsis patients, which are of great value in the prognosis evaluation and deserve further attention.
To analyze the predictive value of stress hyperglycemia ratio (SHR) for major adverse cardiac and cerebrovascular events (MACCE) in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI).
Methods
A total of 271 AMI patients who underwent PCI in Linyi People's Hospital from January 2017 to December 2021 were selected. According to the third quartile of SHR (1.59), they were divided into a high SHR group (SHR ≥ 1.59, 115 cases) and a low SHR group (SHR < 1.59, 156 cases), and their clinical data and outcomes were compared between the two groups. Univariate and multivariate logistic regression methods were used to analyze the influencing factors of MACCE in AMI patients after PCI, and receiver operating characteristics (ROC) curves were used to evaluate the predictive value of SHR for MACCE.
Results
Compared with the low SHR group, patients in the high SHR group showed a significant increase in blood glucose, glomerular filtration rate and ST-segment elevation myocardial infarction (STEMI) and a significant decrease in vascular reconstruction time and low densith lipoprotein (all P < 0.05). The incidence of MACCE in the high SHR group was significantly increased at the 1st, 6th and 12th months after PCI than that in the low SHR group (χ2 = 8.651, 11.208, 15.235; all P < 0.001). The logistic regression analysis showed that the SHR [odds ratio (OR) = 2.231, 95% confidence interval (CI) (1.656, 4.078), P = 0.008], blood glucose [OR = 1.169, 95%CI (1.114, 1.290), P = 0.002], glomerular filtration rate [OR = 1.767, 95%CI (1.522, 2.616), P = 0.041], vascular reconstruction time [OR = 2.688, 95%CI (1.704, 4.145), P = 0.006] and STEMI [OR = 2.113, 95%CI (1.269, 3.381), P = 0.012] were risk factors for the occurrence of MACCE in AMI patients. The ROC curve showed that the critical value for evaluating the occurrence of MACCE in AMI patients using SHR was 1.92, with the sensitivity of 0.782, specificity of 0.830, area under the curve of 0.865 and 95%CI of 0.772-0.962 (P = 0.003).
Conclusion
SHR is an effective predictive indicator for the risk of MACCE in AMI patients undergoing PCI.
To evaluate the value of RETRA score in predicting the prognosis of trauma patients in ICU.
Methods
The clinical data of 903 trauma patients in ICU of Chenzhou Hospital Affiliated to University of South China from January 2020 to August 2022 were retrospectively analyzed, and they were divided into a death group (n = 62) and a survival group (n = 841) according to the 30 d prognosis after injury. The basic clinical data, laboratory tests, abbreviated injury scale (AIS), injury severe score (ISS), and RETRA score were compared between the two groups. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of different trauma scores in assessing the 30 d prognosis of trauma patients, and the Z-test was used to compare the area under the curve (AUC).
Results
The age, systolic blood pressure, diastolic blood pressure, mean arterial pressure, prothrombin time (PT), activated partial thromboplastin time (APTT), length of hospital stay, mechanical ventilation time, RETRA score, ISS score, main injury site of head and abdomen, age 55-65, 66-75 and > 75 years, prehospital endotracheal intubation, unilateral and bilateral pupil dilation, Glasgow coma score ≤ 8, AIS head score ≥ 3, and rates of circulatory failure, coagulation disorders, mechanical ventilation and respiratory failure showed statistically significant differences between the two groups (all P < 0.05). The ROC analysis showed that the RETRA score was the best predictor for 30 d prognosis of trauma patients, with an AUC of 0.849 [95% confidence interval (CI) (0.798, 0.900), P < 0.001], sensitivity of 75.8%, specificity of 78.1%, and a cut-off value of 3.5, followed by the ISS score with an AUC of 0.627 [95%CI (0.552, 0.703), P < 0.001], sensitivity of 58.1%, specificity of 70.7%, and a cut-off value of 23.0. The AIS score had no predictive effect (P = 0.677). The Z-test showed that the RETRA score was better than the ISS score and AIS score (Z = 7.677, 5.237; both P < 0.001).
Conclusion
The RETRA score has a high predictive value for 30 d prognosis of trauma patients in ICU.