Cold ischemia-reperfusion injury (CIRI) is a major contributor to delayed graft function and long-term graft failure after kidney transplantation.Its pathogenesis involves multiple mechanisms, including energy metabolism disorders, oxidative stress and sterile inflammatory responses.Increasing evidence indicates that immune cells play a central regulatory role in the initiation and progression of CIRI.Damage-associated molecular patterns released during cold ischemia and reperfusion activate innate immunity, leading to the rapid recruitment of neutrophils, macrophages, dendritic cells and amplification of inflammatory cascades.Subsequently, adaptive immune cells, including T cells and B cells, are activated and further contribute to sustained inflammation, disruption of immune tolerance and graft injury.Through cytokine signaling, chemokine-mediated recruitment and antigen presentation, different immune cell subsets form a complex interactive network that ultimately determines the severity and outcome of CIRI.This review summarizes the roles and mechanisms of innate and adaptive immune cells in renal allograft CIRI, highlights their interconnections, and discusses emerging immune cell-targeted therapeutic strategies, aiming to provide a theoretical basis for improving clinical outcomes in kidney transplantation.

Objectives:To analyze the cardiac involvement of patients with Fabry disease(FD)in Anhui region.Methods:This retrospective analysis included 48 previously and currently diagnosed FD patients(25 males)in Anhui region,overall patient and gender specific cardiac involvement was analyzed.Results:The median age of FD patients is 28.0(19.0,46.0)years.The cardiac manifestations of patients with FD were most commonly characterized by palpitations/arrhythmias(13/42 cases)and exertional dyspnea(11/42 cases),electrocardiographic changes were most commonly characterized by T-wave inversion(22/42 cases),ST-segment depression(16/42 cases),and left ventricular hypervoltage(18/42 cases),cardiac structural and functional changes were most common in papillary muscle hypertrophy(29/36 cases),bilateral sign(22/37 cases)and left ventricular hypertrophy(21/46 cases),as well as reduced left ventricular global longitudinal strain(26/39 cases).Neuropathic pain(28/43 cases)was the most common extracardiac manifestation of FD patients.FD patients of different gender differed in age at diagnosis(P=0.018),alpha galactosidase A activity(P<0.001),globotriaosylsphingosine(lyso-GL3)levels(P<0.001),enzyme replacement therapy rate(P=0.043),dyshidrosis(P<0.01),and the incidence of angiokeratoma(P=0.004).Correlation analysis showed that genotype was not correlated with enzyme activity or Lyso-GL-3 levels,whereas the Sokolow-Lyon index was positively correlated with Lyso-GL-3 levels(ρ=0.423,P=0.008),and the Sokolow-Lyon indices(septal thickness:ρ=0.562,P<0.001;left ventricle posterior wall thickness:ρ=0.569,P<0.001)and QRS duration(septal thickness:ρ=0.543,P<0.001;left ventricle posterior wall thickness:ρ=0.557,P<0.001)were positively correlated with left ventricular wall thickness.Conclusions:Cardiac involvement in patients with FD in the Anhui region is characterised by palpitations or arrhythmias,accompanied by nonspecific electrocardiographic changes.Echocardiography frequently reveals papillary muscle hypertrophy.The manifestation of cardiac involvement in patients of different genders is similar.

Objectives:To analyze the cardiac involvement of patients with Fabry disease(FD)in Anhui region.Methods:This retrospective analysis included 48 previously and currently diagnosed FD patients(25 males)in Anhui region,overall patient and gender specific cardiac involvement was analyzed.Results:The median age of FD patients is 28.0(19.0,46.0)years.The cardiac manifestations of patients with FD were most commonly characterized by palpitations/arrhythmias(13/42 cases)and exertional dyspnea(11/42 cases),electrocardiographic changes were most commonly characterized by T-wave inversion(22/42 cases),ST-segment depression(16/42 cases),and left ventricular hypervoltage(18/42 cases),cardiac structural and functional changes were most common in papillary muscle hypertrophy(29/36 cases),bilateral sign(22/37 cases)and left ventricular hypertrophy(21/46 cases),as well as reduced left ventricular global longitudinal strain(26/39 cases).Neuropathic pain(28/43 cases)was the most common extracardiac manifestation of FD patients.FD patients of different gender differed in age at diagnosis(P=0.018),alpha galactosidase A activity(P<0.001),globotriaosylsphingosine(lyso-GL3)levels(P<0.001),enzyme replacement therapy rate(P=0.043),dyshidrosis(P<0.01),and the incidence of angiokeratoma(P=0.004).Correlation analysis showed that genotype was not correlated with enzyme activity or Lyso-GL-3 levels,whereas the Sokolow-Lyon index was positively correlated with Lyso-GL-3 levels(ρ=0.423,P=0.008),and the Sokolow-Lyon indices(septal thickness:ρ=0.562,P<0.001;left ventricle posterior wall thickness:ρ=0.569,P<0.001)and QRS duration(septal thickness:ρ=0.543,P<0.001;left ventricle posterior wall thickness:ρ=0.557,P<0.001)were positively correlated with left ventricular wall thickness.Conclusions:Cardiac involvement in patients with FD in the Anhui region is characterised by palpitations or arrhythmias,accompanied by nonspecific electrocardiographic changes.Echocardiography frequently reveals papillary muscle hypertrophy.The manifestation of cardiac involvement in patients of different genders is similar.

Objective:To establish a predictive model for myocardial contusion (MC) in patients with rib fractures and evaluate its clinical application value.Methods:A retrospective case-control study was conducted to analyze the clinical data of 370 patients with rib fractures admitted to the Affiliated Jiangsu Shengze Hospital of Nanjing Medical University from January 2017 to December 2019, including 257 males and 113 females, aged 18-95 years [(56.5±14.0)years]. All the patients underwent electrocardiogram examination and myocardial biomarker test within 24 hours on admission, of whom 159 were diagnosed with MC, and 211 with non-MC (NMC). The 370 patients were divided into a training set of 264 patients (106 with MC, 158 with NMC) and a validation set of 106 patients (53 with MC, 53 with NMC) at a ratio of 7∶3 through the completely randomized method. In the training set, the MC group and NMC group were compared in terms of their demographic characteristics, vital signs on admission, types of rib fractures, number of rib fractures, locations of rib fractures, associated thoracic injuries, trauma scores, and laboratory indices. Variables of positive correlation with MC in patients with rib fractures were screened by Spearman correlation analysis, followed by univariate binary Logistic regression analysis for these variables to determine the risk factors for MC in patients with rib fractures. LASSO regression analysis and multivariate Logistic regression analysis were applied to identify the independent risk factors for MC in patients with rib fractures, and the regression equation was constructed. A nomogram prediction model was plotted based on the regression equation with R software. The receiver operating characteristic (ROC) curve was plotted to evaluate the model′s discriminability. Hosmer-Lemeshow (H-L) goodness-of-fit test and calibration curves of 1000 repeated samplings by the Bootstrap method were used to evaluate the calibration of the model. The decision curve analysis (DCA) and clinical impact curve analysis (CIC) were plotted to evaluate its clinical efficacy. A risk scoring was performed according to the assigned β coefficient of independent risk factors. Accordingly, the 370 selected patients with rib fractures were divided into low-risk subgroup of 202 patients, moderate-risk subgroup of 108 patients, high-risk subgroup of 50 patients, and extremely high-risk subgroup of 10 patients. The incidence of MC and in-hospital mortality were compared among different subgroups so as to further verify the clinical application value of the predictive model.Results:In the training set, there were significant differences between the MC group and NMC group in bilateral rib fractures, flail chest, number of rib fractures, upper chest proximal sternum segment, upper chest anterolateral segment, upper chest proximal spinal segment, middle chest anterolateral segment, middle chest proximal spinal segment, lower chest anterolateral segment, pneumothorax, mediastinal emphysema, hemothorax, sternal fractures, chest abbreviated injury scale (c-AIS), injury severity score (ISS), new injury severity score (NISS), white blood cell counts, hemoglobin, hematocrit, total cholesterol, low density lipoprotein, albumin, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen ( P<0.05 or 0.01). Spearman correlation analysis showed that the bilateral rib fractures, flail chest, number of rib fractures, upper chest proximal sternum segment, upper chest anterolateral segment, upper chest proximal spinal segment, middle chest anterolateral segment, middle chest proximal spinal segment, lower chest anterolateral segment, pneumothorax, hemothorax, sternal fractures, c-AIS, ISS, NISS, white blood cell count, aspartate aminotransferase and blood urea nitrogen were positively correlated with MC ( P<0.05 or 0.01). Univariate binary Logistic regression analysis verified that the above variables with positive correlation were significantly correlated with MC in patients with rib fractures ( P<0.05 or 0.01). The 4 predictor variables screened by LASSO regression analysis were the upper chest anterolateral segment, middle chest proximal spinal segment, pneumothorax, and sternal fractures. Multivariate Logistic regression analysis confirmed that the aforementioned 4 predictor variables were independent risk factors for MC in patients with rib fractures ( P<0.05 or 0.01). The regression equation of the training set was established based on the above independent risk factors: P=e x/(1+e x), with the x=1.57×"upper chest anterolateral segment"+0.73×"middle chest proximal spinal segment"+1.36×"pneumothorax"+2.16×"sternal fractures"-1.10. In the predictive model for MC in patients with rib fractures established based on the equation, the area under the ROC curve (AUC) was 0.77 (95% CI 0.72, 0.83) and 0.77 (95% CI 0.71, 0.82) in the training set and validation set. The H-L goodness-of-fit test showed χ2=2.77, P=0.429 in the training set, and χ2=1.33, P=0.515 in the validation set, indicating that there was no significant difference between the predicted probability and the actual probability of the model ( P>0.05). The calibration curves showed that the bias-corrected curves of the training set and validation set were in good consistency with the actual curves and were both close to the ideal curves. The DCA of the training set and the validation set showed that within the threshold probability range of 0.2-0.8, the predictive model could obtain good net clinical benefits. The CIC of the training set and the validation set indicated that when the threshold probability was >0.4, the population identified as high-risk MC patients by the predictive model highly matched the actual MC patients. Risk scoring of subgroups found that the incidence of MC and in-hospital mortality among the patients with rib fractures were 80.0% and 6.0% in the high-risk subgroup and 90.0% and 20.0% in the extremely high-risk subgroup, significantly higher than those in the low-risk subgroup (24.8%, 1.0%) and the moderate-risk subgroup (55.6%, 1.9%) ( P<0.05). Conclusions:The predictive model for MC in patients with rib fractures constructed based on the upper chest anterolateral segment, middle chest proximal spinal segment, pneumothorax, and sternal fractures has good predictive efficacy and clinical application value.

Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide. Influenza A virus (IAV) has been found to activate multiple programmed cell death pathways, including ferroptosis. Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. However, little is known about how influenza viruses induce ferroptosis in the host cells. In this study, based on network pharmacology, we predicted the mechanism of action of Maxing Shigan decoction (MXSGD) in IAV-induced ferroptosis, and found that this process was related to biological processes, cellular components, molecular function and multiple signaling pathways, where the hypoxia inducible factor-1(HIF-1) signaling pathway plays a significant role. Subsequently, we constructed the mouse lung epithelial (MLE-12) cell model by IAV-infected in vitro cell experiments, and revealed that IAV infection induced cellular ferroptosis that was characterized by mitochondrial damage, increased reactive oxygen species (ROS) release, increased total iron and iron ion contents, decreased expression of ferroptosis marker gene recombinant glutathione peroxidase 4 (GPX4), increased expression of acyl-CoA synthetase long chain family member 4 (ACSL4), and enhanced activation of hypoxia inducible factor-1α (HIF-1α), induced nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) in the HIF-1 signaling pathway. Treatment with MXSGD effectively reduced intracellular viral load, while reducing ROS, total iron and ferrous ion contents, repairing mitochondrial results and inhibiting the expression of cellular ferroptosis and the HIF-1 signaling pathway. Finally, based on animal experiments, it was found that MXSGD effectively alleviated pulmonary congestion, edema and inflammation in IAV-infected mice, and inhibited the expression of ferroptosis-related protein and the HIF-1 signaling pathway in lung tissues.
Animals ; Mice ; Ferroptosis ; Network Pharmacology ; Reactive Oxygen Species ; Vascular Endothelial Growth Factor A ; Influenza A virus ; Iron ; Hypoxia

Objective : To analyze the length of hospital stay of patients with heart failure in a multicenter cohort in order to explore the influencing factors of length of stay and provide data support for further intervention. Methods: A total of 2 794 patients enrolled in the multicenter prospective heart failure cohort were divided into two groups: long hospital stay group (≥9 days) and short hospital stay group ( < 9 days) . The general data of the two groups were compared, and the factors with statistical difference in univariate analysis were included in Logistic multifactor regression analysis to explore the difference in length of hospital stay between the two groups. According to left ventricular ejection fraction(LVEF), patients were divided into heart failure with preserved reduced ejection fraction (HFpEF)group, heart failure with mildly reduced ejection fraction(HFmrEF)group and heart failure with reduced ejection fraction(HFrEF) group, and Logistic multifactor regression analysis was performed to find influencing factors. Results : Logistic multifactor regression analysis showed that LVEF, pneumonia, N⁃terminal pro⁃B⁃type natriuretic peptide(NT⁃proBNP), serum sodium, cardiac resynchronization therapy( CRT) or implantable cardioverter defibrillator(ICD)implantation, β blockers, aldosterone receptor antagonists, positive inotropic drugs and vasodilators were all factors influencing the hospitalization of HF patients. In the HFpEF, HFmrEF, and HFrEF groupsCRT/ICD implantation, positive inotonic drugs, and vasodilator use were suggested to be common factors affecting length of hospital stay in all three groups. Conclusion LVEF, pneumonia, NT⁃proBNP, serum sodium, CRT or ICD implantation, β blockers, aldosterone receptor antagonists, positive inotropic drugs and vasodilators are the influencing factors of hospitalization time in HF patients.

Objective:To explore the risk factors of hemothorax after rib fracture and evaluate its predictive value for hemothorax.Methods:A retrospective case control study was made on the data of 449 patients with rib fracture admitted to Jiangsu Shengze Hospital affiliated to Nanjing Medical University from January 2018 to November 2019. There were 308 males and 141 females，with the age range of 19-97 years［（57.4±14.0）years］. The hemothorax was defined as pleural effusion on chest CT or X examination on admission or within one week after admission. There were 330 patients in hemothorax group and 119 patients in non-hemothorax group. Indices were compared between the two groups，including gender，age，occupation，weight，height，underlying diseases［diabetes，chronic obstructive pulmonary disease（COPD），hypertension，hyperlipidemia］，causes of injury，imaging findings［number of rib fracture，flail chest，bilateral rib fractures，locations of rib fracture and intramural injuries（pneumothorax，pulmonary contusion，mediastinal emphysema and myocardial contusion）］，thoracic cavity drainage，injury to admission time，vital signs（blood pressure and heart rate），routine blood［white blood cell，hemoglobin（Hb），platelet，hematocrit（Hct）］，blood type，urine routine（urinary occult blood，urinary protein，urinary ketone body），biochemical examination［total cholesterol（TCHO），triglyceride（TG），high density lipoprotein（HDL-C），low-density lipoprotein（LDL-C），albumin（ALB），total bilirubin（TBIL），glutamic oxalacetic transaminase（AST），alanine transaminase（ALT），urea nitrogen（BUN），creatinine（CRE），glycosylated hemoglobin（HbA1C）］，coagulation tests［prothrombin time（PT），fibrinogen（FIB），plasma D-dimer（D-D），thrombin time（TT）］after admission，trauma score［chest wall injury score（CIS），injury severity score（ISS），new injury severity score（NISS）］and length of hospital stay. The univariate analysis was used to observe the correlation between each factor and hemothorax after rib fracture and to screen the significant correlation factors，followed by multivariate logistic regression analysis to further identify the independent risk factors. The receiver operating characteristic（ROC）curve was used to analyze the predictive value of continuous variables in independent risk factors and to calcuate the optimal threshold.Results:The two groups showed no significant differences in gender，occupation，weight，height，diabetes，COPD，hyperlipidemia，injury to admission time，blood pressure，heart rate，platelet，urine protein，urine ketone body，TCHO，HDL-C，TBIL，ALT，CRE，HbA1C or PT（ P>0.05）. The hemothorax group showed significantly decreased Hb，Hct，TG，LDL-C and TT and significantly increased age，number of rib fracture，white blood cell count，AST，FIB，D-D，trauma score（CIS，ISS，NISS）and length of hospital stay when compared to non-hemothorax group（ P<0.05）. There were significant differences in hypertension，causes of injury，flail chest，bilateral rib fractures and locations of rib fracture and urinary occult blood between the two groups（ P<0.05）. The univariate analysis showed that age，hypertension，number of rib fractures，flail chest，bilateral rib fractures，locations of rib fracture（upper chest anterolateral segment，middle chest anterolateral segment，middle chest posterolateral segment，middle chest proximal spinal segment，lower chest posterolateral segment，lower chest proximal spinal segment），pneumothorax，pulmonary contusion，myocardial contusion，thoracic cavity drainage，white blood cell count，urinary occult blood，BUN，FIB，trauma score（CIS，ISS，NISS）and length of hospital stay were significantly associated with hemothorax（ P<0.05）. The multivariate Logistic regression analysis showed that locations of rib fracture（including middle chest posterolateral segment，middle chest proximal spinal segment，lower chest posterolateral segment and lower chest proximal spinal segment），pulmonary contusion，thoracic cavity drainage，BUN and trauma score（CIS，ISS，NISS）were significantly associated with hemothorax after rib fracture（ P<0.05）. The ROC curve analysis of continous variables in independent risk factors showed BUN area under the curve（AUC）of 0.587（95% CI 0.529-0.645），CIS AUC of 0.824（95% CI 0.779-0.870），ISS AUC of 0.789（95% CI 0.739-0.840）and NISS AUC of 0.876（95% CI 0.835-0.917）（ P<0.05），and the optimal thresholds for the above variables were 5.0 mmol/L，2.5 points，15 points and 21.5 points，respectively. Conclusion:Locations of rib fracture（including the middle chest posterolateral segment，middle chest proximal spinal segment，lower chest posterolateral segment，lower chest proximal spinal segment），pulmonary contusion，thoracic cavity drainage，BUN，trauma score（CIS，ISS，NISS）are independent risk factors for hemothorax after rib fracture. BUN>5.0 mmol/L and trauma score（CIS>2.5 points，ISS>15 points，NISS>21.5 points）have significant values in predicting hemothorax.

Objectives To investigate the changes of erythropoietin(EPO)expression in rats after focal cerebral ischemia/reperfusion injury.Methods Male Sprague-Dawley rats were randomly divided into normal,sham,cerebral ischemic/reperfusion(CIR)groups.Middle cerebral artery occlusion(MACO)model was established by Longa's method,and reperfusion was followed 2 hours after occlusion in CIR group.The rats' brain neurological deficit scores were evaluated at 24 h,48 h,72 h and 96 h after reperfusion.The protein expression of EPO was determined by immunohistochemistry staining and Western blotting in each time points.Results The rats' brain neurological deficit scores at 48 h,72 h and 96 h were significantly increased(3.40±0.32,3.60±0.17,3.70±0.21,all P<0.05)compared with those at 24 h(3.00±0.22)after reperfusion in CIR group.The results of immunohistochemistry staining and Western blotting showed that the positive expression of EPO proteins in rats started at 24 h(0.36±0.05,140.20±0.30)after cerebral ischemic/reperfusion injury,increased significantly at 48 h(1.09±0.10,145.40±0.16),reached the peak at 72 h(1.29±0.09,156.23±0.12),began to decline at 96 h(0.98±0.04,141.56±0.36).Conclusions Cerebral ischemia and reperfusion injury can induce increased expression of EPO protein,which suggests that EPO may have protective effect on nerve cells under the condition of ischemia and reperfusion.