To investigate the protective effects and mechanisms of Maresin conjugates in tissue regeneration 3 (MCTR3) on the degradation of pulmonary vascular endothelial glycocalyx in mice with lipopolysaccharide (LPS)-induced acute respiratory distress syndrome(ARDS).
Methods
A total of 120 C57BL/6 mice were divided into four groups according to a random number table: a Control group， a LPS group， a LPS + MCTR3 group， and a MCTR3 group， with 30 mice in each group.The Control and MCTR3 groups received intratracheal administration of isotonic NaCl solution (50 μL)， while the LPS and LPS + MCTR3 groups intratracheally received LPS (1 mg/kg in 50 μL saline) to establish a ARDS model.Additionally，the LPS + MCTR3 and MCTR3 groups intravenously received MCTR3 (8 mg / kg).All groups were sampled 6 hours later.The clinical prognosis and related pathological changes were observed in each group.Electron microscopy was used to observe the structure of pulmonary vascular endothelial glycocalyx and alveolar epithelial cell mitochondria.
Results
After administering isotonic NaCl solution intratracheally for 4 days， there were no deaths in the Control and MCTR3 groups， whereas only one mouse survived in the LPS group， and four mice survived in the LPS + MCTR3 group.The difference in 4-d survival among the groups was statistically significant (χ2=22.810， P ＜0.001).Moreover， the 4-d survival of mice in the LPS group was significantly decreased compared with the Control and MCTR3 groups； the 4-d survival of mice in the LPS+MCTR3 group was significantly better than that of the LPS group (all P ＜0.001).The arterial partial pressure of oxygen (PaO2)， oxygenation index， pathological injury scores， lung tissue wet/dry weight (W/D) ratio， tumor necrosis factor-alpha (TNF-α)， interleukin-1 beta (IL-1β)， endothelial glycocalyx degradation products of heparan sulfate proteoglycan 2(HSPG2) and syndecan-1 (SDC-1)， glycocalyx degradation marker heparanase (HPA)， endothelial glycocalyx-related protein SDC-1， mitochondrial-associated proteins of Sirtuin 1 (SIRT1)， peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)， nuclear respiratory factor 1(NRF1)， NRF2 and mitochondrial transcription factor A (TFAM)， and Flameng scores showed statistically significant differences among these four groups (F=8.812， 21.470， 123.451， 148.994，57.906， 92.948， 47.971， 88.109， 26.839， 31.928， 12.444， 5.537， 9.865， 12.423， 16.352， 294.910；all P ＜0.001).Further pairwise comparisons revealed that compared to the LPS group， the PaO2，oxygenation index， and protein expression levels of SDC-1， SIRT1， PGC-1α， NRF1， NRF2 and TFAM were significantly higher， while the lung tissue pathological injury scores， W/D ratio， TNFα， IL-1β， HSPG2， SDC-1， HPA protein， and Flameng scores were reduced in the LPS + MCTR3 group (all P ＜0.05).
Conclusions
MCTR3 can improve clinical outcomes and pathological changes in ARDS mice， promoting the resolution of inflammation.Its potential mechanism may involve improving mitochondrial function in alveolar epithelial cells and reducing glycocalyx degradation in the pulmonary vasculature of ARDS mice.
To explore the effect of hydrogen inhalation therapy on the expression of autophagy-related proteins and motor function recovery after spinal cord injury in rats.
Methods
Forty-five female rats were randomly divided into a control group (Sham group)，a spinal cord injury group (SCI group) and a hydrogen-treated group (SCI+H2 group)， with 15 rats in each group.The Sham group only performed laminectomy without injury to the spinal cord.The SCI group and the SCI + H2 group used the modified Allen method to injury the spinal cord in the T10 segment and established a spinal cord injury model.The SCI group did not undergo any treatment after injury， whereas rats in the SCI+H2 group were given inhalation of hydrogen for 30 minutes twice a day.The hindlimb motor function of rats in each group was evaluated by the Basso-Beattie-Bresnahan (BBB) score at 1， 3， 7 and 14 days after injury.At 3 d after injury， the ratio of microtubule-associated protein 1 light chain 3 (LC3)-II to LC3-I and the expression of polyubiquitin-binding protein P62 and Beclin-1 were detected by western-blotting.Quantitative real-time PCR was used to detect the expression of Beclin-1 and LC3 messenger RNA (mRNA) in the injured area of rats in each group.The number of positive cells of LC3 and Beclin-1 in the injured area of each group was detected by immunofluorescence staining.
Results
At 1， 3， 7， and 14 days after injury， the BBB scores of the rats in the three groups were compared， and the differences were statistically significant (F=1 055.216， 771.909， 446.000，215.438； all P ＜0.001).Further two-by-two comparisons showed that the BBB score of the SCI group and SCI+H2 group was lower than that of the Sham group at all time points after injury，and the BBB score was significantly higher in the SCI + H2 group than in the SCI group at 7 and 14 days after injury (all P ＜0.05).At 3 d after injury， the LC3-II/LC3-I ratio， P62 protein，Beclin-1 protein， LC3 mRNA and Beclin-1 mRNA were compared among the three groups， and the differences were statistically significant (F=384.212， 49.279， 28.249， 17.904， 50.674； all P ＜0.001).Further two-by-two comparisons revealed that compared with the Sham group， the LC3-II/LC3-I ratio， Beclin-1 protein and the expression of LC3 and Beclin-1 mRNA were significantly higher in the SCI group and the SCI + H2 group， and the expression of P62 protein was significantly lower (all P ＜0.05).Compared with the SCI group， the LC3-II/LC3-I ratio， Beclin-1 protein and the expression LC3 and Beclin-1 mRNA were significantly decreased， while the P62 protein expression was significantly increased in the SCI+H2 group (all P ＜0.05).At 3 d after injury， immunofluorescence staining showed that LC3 and Beclin-1 positive cells in the Sham group were less than those in spinal cord injury groups， and they were significantly higher in the SCI group than in the SCI+H2 group.
Conclusions
Autophagy is activated in the injured area after spinal cord injury with nerve damage in rats.Hydrogen inhalation can regulate the overactivation of autophagy and promote it to a homeostatic environment， which is beneficial to the recovery of spinal cord injury.
To investigate risk factors of early survival of sepsis patients and develop a Cox risk prediction model.
Methods
Data of 226 septic patients who were admitted to the ICU of the Affiliated Hospital of Nanjing University of Chinese Medicine from January 2018 to December 2021 were retrospectively analyzed.According to their early survival (28 days) outcomes， patients were divided into a survival group (n=183) and a death group (n=43).Univariate and multivariate Cox regression was used to explore independent risk factors of early survival of sepsis patients.A random forest algorithm was used to screen predictive variables and a nomogram was constructed.A calibration curve， a Brier score and a continuous rank probability score (CRPS) curve were constructed to evaluate the distinction and calibration of the nomogram.A clinical decision curve was drawn to evaluate the clinical applicability of the nomogram.
Results
Multivariate Cox regression showed that age ［hazard ratio (HR) = 1.032，95% confidence interval (CI) (1.004， 1.062)， P = 0.025］ and sequential organ failure assessment (SOFA) score ［HR = 1.165， 95%CI (1.017， 1.335)， P = 0.027］ were independent risk factors of early survival of sepsis patients.Six predictive variables (age， SOFA score， brian natriuretic peptide， lactatic acid， activated partial thromboplastin time and D-Dimer) were screened by the random forest algorithm and a nomogram was constructed.The calibration curve showed that the nomogram had a good fitting degree.The Brier score and CRPS curve showed that the total Brier score was less than 0.20 and the total CRPS was less than 0.15.The clinical decision curve showed that the prediction model had good clinical applicability.
Conclusion
The Cox risk model for early survival of sepsis patients has good clinical predictive ability and applicability.
To analyze the efficacy and safety of obinutuzumab in the treatment of patients with phospholipase A2 receptor (PLA2R) associated membranous nephropathy (MN).
Methods
It was a single-center retrospective observational study.The clinical data before and after obinutuzumab treatment of 12 patients with PLA2R associated MN in the Department of Nephrology of People's Hospital of Anji from April 2022 to November 2023 were retrospectively collected.The kidney relief situation and adverse reactions were analyzed.The treatment regimen was 1.0 g intravenous infusion of obinutuzumab initially， with or without additional dosage.The follow-up was up to March 12， 2024.
Results
All 12 patients had positive renal puncture pathology PLA2R staining and/or positive serum anti-PLA2R antibodies and were diagnosed with PLA2R associated MN.Ten patients were treated with a 2nd dose of obinutuzumab， one was treated in another hospital without a 2nd dose of obinutuzumab， and one was treated with an additional 3rd dose of obinutuzumab after eight months of treatment.None of the 12 patients experienced serious adverse events， and two had infections which were grade 3 by the common terminology criteria for adverse events.Grade 1 infusion related reactions (IRR) occurred in five patients during the initial treatment， which were alleviated after slowing down the infusion rate or symptomatic treatment， and they successfully completed the infusion.No IRR or adverse events occurred in subsequent infusions.Ten patients achieved remission after treatment， including four complete remissions， and the other two could not be evaluated for efficacy due to missing followup data.
Conclusion
Obinutuzumab treatment is effective for PLA2R associated MN in inducing kidney remission， with favorable safety.
To evaluate the efficacy of levosimendan in the treatment of pulmonary hypertension (PH) combined with right heart failure.
Methods
PubMed， Embase，Web of Science， Cochrane Library， Wanfang， VIP and CNKI databases were searched for studies on the efficacy of levosimendan in the treatment of patients with right heart failure and PH published up to November 30， 2022.The Jüni scale was used to evaluate the quality of the included literature.The Review Manager 5.4 software was used for data analysis.
Results
A total of 10 studies were included， containing 681 patients with PH and right heart failure.The meta-analysis showed that after levosimendan treatment， their mean pulmonary artery pressure［standard mean difference (SMD)= -1.35， 95% confidence internal (CI) (-2.55， -0.15)， Z = 2.20，P=0.03］， systolic pulmonary artery pressure ［SMD=-0.82， 95%CI (-1.09， -0.55)， Z=5.93， P ＜0.000 01］ and N-terminal pro-brain natriuretic peptide ［SMD = -0.80， 95%CI (-1.17， -0.42)， Z =4.12， P ＜0.000 1］ were significantly decreased， while their tricuspid annular plane systolic excursion［SMD=0.49， 95%CI (0.29， 0.68)， Z=4.88， P ＜0.000 01］， mixed venous oxygen saturation ［SMD=0.60， 95%CI (0.32， 0.89)， Z = 4.12， P ＜0.000 1］ and 6-minute walking distance ［SMD = 0.62，95%CI (0.40， 0.84)， Z=5.52， P ＜0.000 01］ were significantly increased.
Conclusion
Levosimendan can significantly reduce pulmonary artery pressure， improve right ventricular function and increase exercise tolerance in patients with PH and right heart failure.
To identify factors associated with hemorrhage in adult patients with extracorporeal membrane oxygenation (ECMO) by a meta-analysis.
Methods
Wanfang， CNKI，China Biomedical Literature Database， VIP， PubMed， Web of Science， Cochrane Library， Embase，CINAHL， and Ovid databases were searched for relative studies on risk factors or predictors of hemorrhage in adult ECMO patients from January 1， 2013 to December 31， 2023.After literature search， screening， and data extraction by two researchers， a meta-analysis was performed using RevMan 5.3.
Results
Twenty-two articles were included， with 13 238 adult ECMO patients.The meta-analysis showed that diabetes， fungal pneumonia， renal failure， rapid decline of arterial partial pressure of carbon dioxide within 2 hours after ECMO initiation， low fibrinogen during support， platelet ＜100 g / L， ECMO after cardiac surgery， and longer duration of ECMO support were risk factors for hemorrhage in adult ECMO patients (all P ＜0.05).Arteriovenous ECMO was also a risk factor for hemorrhage after removing heterogeneous sources (P ＜0.05).
Conclusion
There are many risk factors for bleeding in adult ECMO patients， which can be used as a reference for medical staff to identify high-risk groups and formulate early intervention measures to reduce the occurrence of adverse events.
