Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

Objective To study the correlation between the post-transplant renal allograft function and the variation of serum cystatin C (CyC) concentration in renal allograft recipients. Methods One hundred and ninety-three renal allograft recipients accepted the same combination immunosuppressive regimen of tacrolimus, mycophenolate and prednisone were enrolled into the study. Patient's serum and urine samples were collected on day 5 post-transplant to detect serum cystatin C, serum and urine creatinine (SCr). Correlation analysis was used to analyze correlation between CyC concentration and SCr concentration or the calculated creatinine clearance rate (CkCCr) by using the Cockcroft-Gault equation and urine creatinine clearance rate (CCr). Specificity and sensitivity of using the CyC concentration to evaluate glomerular filtration rate (GFR) were calculated as well.Results The mean concentrations of serum CyC and SCr on day 5 post-transplant were (1.91±1.2)mg/L and (174.0±129.1)μmol/L, respectively. While the CCr and CkCCr were (67.9±27.3)ml/min and (68.1±27.8)ml/min, respectively. Forty-two patients had a CyC concentration below 1.25 mg/L, 102 patients'CyC concentrations were between 1.25 and 2.0 mg/L and 49 patients'CyC concentrations were above 2. 0 mg/L. As for SCr, 62 patients had a concentration below 125 μmol/L, 83 patients'concentrations were between 125 and 200 μmol/L and 48 patients'concentrations were above 200 μmol/L. For CkCCr, there were 52 cases with a concentration above 80 ml/min, 96 cases with a concentration between 80 and 60 ml/min and 45 cases with a concentration below 60 ml/min. Serum CyC concentration had a negative correlation with CkCCr (r=-0. 907, P＜0. 001) and had a significantly positive correlation with SCr concentration (r=0. 886, P＜0. 001). SCr had a significantly negative relationship with CkCCr (r=-0. 889 ,P＜0. 001). Serum CyC had higher correlation with CkCCr than the correlation between SCr and CkCCr. The ROC curves showed that areas under curve of CyC, SCr, CCr and CkCCr were 0. 877, 0. 771, 0. 832 and 0. 909, respectively. Specificity and sensitivity of CyC, SCr,CCr and CkCCr were 69.3%, 96.1%, 77.1%, 71.3%and 91.6%, 52.2%, 67.5%, 84.6%, respectively.Conclusions Serum CyC concentration elevates earlier than SCr concentration when there is slight renal function impairment. Serum CyC concentration might become a more sensitive marker to evaluate the post-transplant renal allograft function in renal transplant recipients.