The immunomodulation role of Th17 and Treg in renal transplantation.

Kidney transplantation (KT) is an ultimate treatment of end-stage chronic kidney disease, which can meet a lot of complications induced by immune system. With under-controlled immunosuppression, the patient will obtain a good prognosis. Otherwise, allograft disfunction will cause severe organ failure and even immune collapse. Acute or chronic allograft dysfunction after KT is related to Th17, Treg, and Th17/Treg to a certain extent. Elevated Th17 levels may lead to acute rejection or chronic allograft dysfunction. Treg mainly plays a protective role on allografts by regulating immune response. The imbalance of the two may further aggravate the balance of immune response and damage the allograft. Controlling Th17 level, improving Treg function and level, and adjusting Th17/Treg ratio may have positive effects on longer allograft survival and better prognosis of receptors.

Cyclic helix B peptide ameliorated the sepsis-induced injury in human HPMEC cells through regulating NF-κB.

BACKGROUND: Sepsis is a life-threatening condition. The incidence of severe sepsis is increasing. Sepsis is often complicated with organ dysfunctions. Cyclic helix B peptide (CHBP) is a peptide derivant of erythropoietin with powerful tissue-protective efficacies. However, the role of CHBP in sepsis-induced injury remains unclear. MATERIAL AND METHODS: Lyso-phosphatidylserine (LPS) was used to induce sepsis in human pulmonary microvascular endothelial cells (HPMECs). Cell growth was detected using Cell Counting Kit-8. Cell permeability was measured using fluorescein isothiocyanate (FITC)-dextran. Cecal ligation and puncture (CLP) method was applied to induce sepsis and CHBP was provided to test its efficacy. Western blot assays were used to evaluate gene expression. RESULTS: Administration of CHBP ameliorated LPS-induced injury in HPMECs dose-dependently. Administration of CHBP decreased the permeability of LPS-treated HPMEC cells in a same way as well. Furthermore, we identified that recombinant CHBP protein (Re-CHBP) ameliorated CLP-induced injury in vivo. Finally, we found that administration of NF-κB activator, TNF-α, abolished the function of Re-CHBP in LPS-treated HPMEC cells. CONCLUSION: CHBP ameliorated sepsis-induced injury dose dependently both in vitro and in vivo through decreasing the permeability of HPMEC cells via suppressing NF-κB signaling and inflammation. Present findings highlight the importance of CHBP/NF-κB signaling in septic injury and provide new insights into therapeutic strategies for sepsis-induced injury.

Preliminary Study on the Combination Effect of Clindamycin and Low Dose Trimethoprim-Sulfamethoxazole on Severe Pneumocystis Pneumonia After Renal Transplantation.

Objective: Evaluate the effect of the combination of clindamycin with low-dose trimethoprim-sulfamethoxazole (TMP/SMX) regimen on sever Pneumocystis pneumonia (PCP) after renal transplantation. Method: 20 severe PCP patients after renal transplantation were included in this historical-control, retrospective study. A 10 patients were treated with the standard dose of TMP/SMX (T group), the other 10 patients were treated with the combination of clindamycin and low dose TMP/SMX (CT group). Results: Although there was no significant difference in the hospital survival between the two groups, the CT protocol improved the PaO2/FiO2 ratio more significantly and rapidly after the 6th ICU day (1.51 vs. 0.38, P = 0.014). CT protocol also ameliorated the pulmonary infiltration and the lactate dehydrogenase level more effectively. Moreover, the CT protocol reduced the incidence of pneumomediastinum (0 vs. 50%, P = 0.008), the length of hospital staying (26.5 vs. 39.0 days, P = 0.011) and ICU staying (12.5 vs. 22.5 days, P = 0.008). Furthermore, more thrombocytopenia (9/10 vs. 3/10, P = 0.020) was emerged in the T group than in the CT group. The total adverse reaction rate was much lower in the CT group than in the T group (8/80 vs. 27/80, P < 0.001). Consequently, the dosage of TMP/SMX was reduced in 8 patients, while only 2 patients in the CT group received TMP/SMX decrement (P = 0.023). Conclusion: The current study proposed that clindamycin combined with low-dose TMP/SMX was more effective and safer the than single use of TMP/SMX for severe PCP patients after renal transplantation (NCT04328688).

Neutrophil-to-Lymphocyte Ratio Predicts Mortality in Adult Renal Transplant Recipients with Severe Community-Acquired Pneumonia.

Mortality of renal transplant recipients with severe community-acquired pneumonia (CAP) remains high, despite advances in critical care management. There is still a lack of biomarkers for predicting prognosis of these patients. The present study aimed to investigate the association between neutrophil-to-lymphocyte ratio (NLR) and mortality in renal transplant recipients with severe CAP. A total of 111 renal transplant recipients with severe CAP admitted to the intensive care unit (ICU) were screened for eligibility between 1 January 2009 and 30 November 2018. Patient characteristics and laboratory test results at ICU admission were retrospectively collected. There were 18 non-survivors (22.2%) among 81 patients with severe CAP who were finally included. Non-survivors had a higher NLR level than survivors (26.8 vs. 12.3, p < 0.001). NLR had the greatest power to predict mortality as suggested by area under the curve (0.88 ± 0.04; p < 0.0001) compared to platelet-to-lymphocyte ratio (0.75 ± 0.06; p < 0.01), pneumonia severity index (0.65 ± 0.08; p = 0.05), CURB-65 (0.65 ± 0.08; p = 0.05), and neutrophil count (0.68 ± 0.07; p < 0.01). Multivariate logistic regression models revealed that NLR was associated with hospital and ICU mortality in renal transplant recipients with severe CAP. NLR levels were independently associated with mortality and may be a useful biomarker for predicting poor outcome in renal transplant recipients with severe CAP.

Lactate dehydrogenase as a prognostic marker of renal transplant recipients with severe community-acquired pneumonia: a 10-year retrospective study.

BACKGROUND: Lactate dehydrogenase (LDH) is an easily accessible biological marker that has been associated with several pulmonary disorders. The aim of this study was to investigate the prognostic value of serum LDH in renal transplant recipients with severe community-acquired pneumonia (CAP). METHODS: A total of 77 renal transplant recipients with severe CAP admitted to the intensive care unit (ICU) were screened for eligibility in this retrospective study. Patient characteristics and laboratory tests, such as LDH on day 1 (LDHday 1) and day 3 (LDHday 3) were recorded. Cox regression models were used to assess the performance of LDH to predict 90-day mortality. RESULTS: Median LDH level was higher on day 1 in 90-day nonsurvivors (440 U/L, IQR, 362-1,055 U/L) than in survivors (334 U/L, IQR, 265-432 U/L; P<0.001); median LDH level on day 3 in nonsurvivors was 522.5 U/L (IQR, 457.5-1,058.5 U/L) and in survivors 290 U/L (IQR, 223-387.5 U/L; P<0.001). Analysis of LDH kinetics from day 1 to day 3 showed an increase in nonsurvivors and a decrease in survivors. Moreover, Multivariate Cox analysis showed that LDHday 1 (increase per 100 U/L), LDHday 3 (increase per 100 U/L) and LDH kinetics (increase per 10%) were independently associated with 90-day mortality. CONCLUSIONS: Serum LDH levels and LDH kinetics early were independently associated with 90-day mortality in renal transplant recipients with severe CAP. In future, the prognostic role of LDH needs to be warranted.

MicroRNA-27a alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis through modulating TLR4/MyD88/NF-κB pathway.

Acute lung injury (ALI) is a critical clinical condition with a high mortality rate, characterized with excessive uncontrolled inflammation and apoptosis. Recently, microRNAs (miRNAs) have been found to play crucial roles in the amelioration of various inflammation-induced diseases, including ALI. However, it remains unknown the biological function and regulatory mechanisms of miRNAs in the regulation of inflammation and apoptosis in ALI. The aim of this study is to identify and evaluate the potential role of miRNAs in ALI and reveal the underlying molecular mechanisms of their effects. Here, we analyzed microRNA expression profiles in lung tissues from LPS-challenged mice using miRNA microarray. Because microRNA-27a (miR-27a) was one of the miRNAs being most significantly downregulated, which has an important role in regulation of inflammation, we investigated its function. Overexpression of miR-27a by agomir-27a improved lung injury, as evidenced by the reduced histopathological changes, lung wet/dry (W/D) ratio, lung microvascular permeability and apoptosis in the lung tissues, as well as ameliorative survival of ALI mice. This was accompanied by the alleviating of inflammation, such as the reduced total BALF cell and neutrophil counts, decreased levels of tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-6) interleukin-1ß (IL-1ß) and myeloperoxidase (MPO) activity in BAL fluid. Toll-like receptor 4 (TLR4), an important regulator of the nuclear factor kappa-B (NF-κB) signaling pathway, was identified as a novel target of miR-27a in RAW264.7 cells. Furthermore, our results showed that LPS stimulation increased the expression of MyD88 and NF-κB p65 (p-p65), but inhibited the expression of inhibitor of nuclear factor-κB-α (IκB-α), suggesting the activation of NF-κB signaling pathway. Further investigations revealed that agomir-miR-27a reversed the promoting effect of LPS on NF-κB signaling pathway. The results here suggested that miR-27a alleviates LPS-induced ALI in mice via reducing inflammation and apoptosis through blocking TLR4/MyD88/NF-κB activation.

[Relationship between blood lactate level and the prognosis of patients with diabetic sepsis].

OBJECTIVE: To evaluate the prognostic value of blood lactate (Lac) level in sepsis patients with or without diabetes. METHODS: 106 patients admitted to intensive care unit (ICU) of Zhongshan Hospital Affiliated to Fudan University from April 2015 to November 2016 were enrolled. The patients with age > 18 years and the length of hospital stay > 24 hours were included. Records including blood Lac, serum creatinine (SCr), white blood cell count (WBC), platelet count (PLT), sequential organ failure assessment (SOFA) on the first day of admission; minimum oxygen index (PaO2/FiO2) in 3 days after admission; mechanical ventilation, whether there was a history of diabetes, usage of biguanides, etiology control treatment, usage of continuous renal replacement therapy (CRRT) were collected. According to the level of blood Lac patients were divided into high Lac group (Lac > 2 mmol/L) and low Lac group (Lac ≤ 2 mmol/L); based on their diabetic history, sepsis patients were divided into the diabetes group and non-diabetes group. The survival curve of each group was analyzed by Kaplan-Meier regression analysis, and the factors influencing the prognosis were analyzed by multivariate Cox regression analysis. RESULTS: There were 76 males and 30 females sepsis patients, with an average age of (68.1±14.7) years old. In the 51 patients of low Lac group, there were 7 patients who suffered from diabetes. While in the 55 patients of high Lac group, there were 12 patients who suffered from diabetes. Compared with low Lac group, high Lac group had a higher age, higher SOFA score, and a lower proportion of patients who had the treatment of etiology control (all P < 0.05). There was no significant difference of blood Lac in sepsis patients with diabetes and those without diabetes (mmol/L: 3.03±2.73 vs. 2.81±2.40, P > 0.05). Kaplan-Meier survival curve analysis showed that the 90-day survival rate in the high Lac group was significantly lower than that in the low Lac group (56.36% vs. 90.20%, χ 2 = 0.697, P = 0.008). The high Lac group without diabetes had lower survival rate, and the 90-day survival rate was significantly lower than that of the low Lac group without diabetes (58.14% vs. 90.90%, χ 2 = 7.152, P = 0.007); there was no significant difference in 90-day survival rate between the high Lac group and the low Lac group with diabetes (50.00% vs. 85.71%, χ 2 = 0.012, P = 0.914). Multivariate Cox regression analysis showed that blood Lac was an independent risk factor for the prognosis of sepsis patients [odds ratio (OR) = 3.863, 95% confidence interval (95%CI) = 1.237-12.060, P = 0.020]. After stratification according to their diabetic history, the blood Lac was an independent risk factor for the prognosis of sepsis patients without diabetes (OR = 4.816, 95%CI = 1.407-15.824, P = 0.010), but the blood Lac had no effect on the prognosis of sepsis patients with diabetes (OR = 0.000, 95%CI = 0.000-1.103, P = 0.270). CONCLUSIONS: The predictive value of blood Lac on sepsis patients with or without diabetes was different. The blood Lac was related with the prognosis of sepsis patients without diabetes, while further study should be conducted for the prognostic value of blood Lac in sepsis patients with diabetes, and it's possible to increase the cut-off-point of Lac level in these patients.