Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

[This corrects the article DOI: 10.1016/j.jpha.2023.08.006.].

Objective: To analyze the results of national external quality assessment (EQA) for transfusion compatibility test from 2018 to 2023, with the aim of providing references for improving laboratory testing quality and ensuring the safety of clinical blood transfusion. Methods: Three EQA programs were conducted annually, each distributing 22 quality assessment samples. Participating transfusion laboratories were required to complete testing within specified deadlines and to submit results along with documentation of testing methodologies, reagents, and equipment used. National Center for Clinical Laboratories (NCCL) conducted statistical analysis of laboratory results, evaluated testing outcomes and related circumstances, and provided feedback to participating laboratories. EQA data from transfusion laboratories across China from 2018 to 2023 were collected and systematically analyzed. Results: From 2018 to 2023, the qualification rates for all five items (ABO forward typing, ABO reverse typing, Rh blood group typing, antibody screening, and cross-matching) were 67.59%, 77.11%, 77.38%, 72.78%, 79.96%, and 85.16%, respectively. The mean qualification rates for ABO forward typing, ABO reverse typing, RhD blood group typing, antibody screening, and cross-matching over the past six years were 96.25%±0.59%, 90.45%±4.52%, 96.05%±0.71%, 90.88%±2.86%, and 88.34%±3.48%, respectively. The qualification rates in 2019, 2020, 2022, and 2023 all showed a stable trend of "blood stations>tertiary hospitals>secondary hospitals". The mean qualification rate of laboratories in secondary hospitals from 2018 to 2023 was significantly lower than those of laboratories in tertiary hospitals and blood stations (P<0.05), while no significant difference was observed between laboratories in tertiary hospitals and blood stations (P>0.05). The micro column agglutination method was the most widely used in all five tests. In the four test items, namely ABO forward typing, ABO reverse typing, antibody screening, and cross-matching, there was a statistically significant difference in the qualification rate of micro column agglutination method compared to other methods (P<0.05). There was a statistical difference in the qualification rate between manual and automated detection using micro column agglutination method in the cross-matching tests (P<0.05), whereas no significant difference was noted for the other test items (P>0.05). Conclusion: From 2018 to 2023, the number of laboratories participating in EQA activities has been increasing year by year, and the qualification rate has shown an overall upward trend. The type of laboratory is a key factor affecting the qualification rate, and the testing capabilities of some laboratories still need to be improved. The micro column agglutination method is widely used in transfusion compatibility tests. The established EQA program effectively monitors quality issues in laboratories, drives continuous improvement, and ensures sustained enhancement of testing standards to safeguard clinical blood safety.

Objective To explore the molecular mechanisms and cell-cell interactions in the injury process of pancreatic islet transplantation.Methods Single-cell transcriptome data from mouse islets treated with inflammatory factors were used,and data processing was performed using the Seurat package,with integrated data to remove batch effects.Cell subpopulations were annotated based on known markers.Cell-cell interactions in the inflammatory factor-treated group were analyzed using the CellChat package,and inferred based on the expression of cell surface receptors and ligands.Gene set enrichment analysis was used to clarify the biological processes enriched in β-cells after treatment with inflammatory factors.Finally,differentially expressed transcription factors were identified and verified using microarray datasets of donor islet ischemic injury and Western blotting.Results A total of 7 different cell subpopulations were found in mouse islets,with β-cells being the most abundant.Cell-cell interaction network analysis showed that the number and strength of interactions between ductal cells and other cells were the highest.Gene set enrichment analysis showed that after treatment with inflammatory factors,the immune response was positively enriched in β-cells,while peptide hormone metabolism,bile acid metabolism,and ion homeostasis were downregulated.The common differential transcription factors identified in the mouse single-cell transcriptome and the microarray dataset of donor islet ischemic injury were early growth response 1(EGR1),nuclear factor-κB inhibitor α(NFKBIA),and activating transcription factor 3(ATF3).Among them,NFKBIA and ATF3 were upregulated,while EGR1 was downregulated.The expression of EGR1 protein was downregulated after 24 h,48 h,and 72 h of cold ischemia.Conclusions EGR1 is a transcription factor closely related to islet cold ischemia,and future research should focus on the specific mechanisms of EGR1 and its downstream target genes,in order to provide more effective strategies for clinical treatment of islet transplantation.

【Objective】 To examine risk factors for acute pancreatitis (AP) in individuals with chronic alcohol consumption habits. 【Methods】 The study incorporated participants from the initial survey (2006-2010) and subsequent follow-ups (2014+) taken from the UK Biobank database, with the observation period ending on November 30, 2022. During this period, 176 individuals were newly diagnosed with AP, while 59,512 remained unaffected. Vital characteristics of the target population, such as their medical histories, surgical experiences and dietary patterns, were collected during the enrolment phase (2006-2010). The Cox proportional hazard model was employed to ascertain whether these characteristics were potent risk factors for AP. Concurrently, a subgroup from the target population with documented drinking behavior was selected. The multivariate Cox proportional hazard model was utilized to analyze the relationship of the established factors, variances in alcohol consumption, and increased alcohol intake (Δ) with the onset of AP, and whether the additional alcohol intake served as a risk factor. 【Results】 Multivariate analysis revealed that consumption quantity of cooked vegetables inversely correlated with AP risk (HR=0.44, 0.39, 0.42 and 0.41 for one, two, three and four+ tablespoons per day, respectively, as compared to non-consumers). Coffee consumption (2-3 cups per day) also reduced AP risk (HR=0.45 for 2 cups/day; HR=0.39 for 3 cups/day as compared to non-coffee drinkers). However, those with biliary disease without cholecystectomy exhibited a marked increase in AP risk (HR=7.82), which reduced albeit remained elevated for those with biliary disease post-cholecystectomy (HR=2.15). Subgroup analysis showed minimal impact of alcohol intake levels on AP incidence. Yet, increased alcohol consumption (Δ of 1 bottle/week) was linked to a heightened AP risk (HR=1.05, 95% CI:1.02-1.09, P<0.05). 【Conclusion】 Among longstanding alcohol consumers, a diet rich in cooked vegetables and moderate coffee consumption offers protective effects against AP. Conversely, biliary disease (particularly without cholecystectomy) and elevated alcohol intake present considerable risk factors for the development of this condition.

AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

BACKGROUND:Endothelin has been found to be involved in the breakdown of the blood-spinal cord barrier after spinal cord injury,and stem cell-derived exosomes can reduce the permeability of the blood-spinal cord barrier and repair spinal cord injury. OBJECTIVE:To investigate whether exosomes produced by human umbilical cord mesenchymal stem cells can reduce the permeability of the blood-spinal cord barrier by inhibiting endothelin-1 expression,thus repairing spinal cord injury. METHODS:Exosomes were extracted from the cultured supernatant by the hyperspeed centrifugation method.The morphology of exosomes was observed by transmission electron microscope.The expression levels of tsg101 and CD63 were detected by western blot assay.Eighty SD rats were randomly divided into sham operation group,model group,exosome group,and endothelin-1 group(n=20).The modified Allen's method was used to create the rat model of spinal cord injury.In the endothelin-1 group,10 μL(1 μg/mL)endothelin-1 was injected directly into the injured area with a microsyringe.Immediately,1 day,2 days after operation,sham operation group and model group were injected with 200 μL PBS solution through the tail vein;the exosome group and endothelin-1 group were injected with 200 μL exosome(200 μg/mL)solution through the tail vein,respectively.Hind limb motor function scores were performed on days 1,3,7,14 and 21 after spinal cord injury.The blood-spinal cord barrier permeability was observed by Evans blue staining on day 7 after injury.The expression levels of tight junction proteins β-Catenin,ZO-1,Occludin and endothelin-1 in the spinal cord were detected by western blot assay. RESULTS AND CONCLUSION:(1)Basso-Beattie-Bresnahan score in the exosome group was significantly higher than that in the model group at 3-21 days after injury(P<0.05).Hematoxylin-eosin staining showed that spinal cord injury was greatly reduced in the exosome group compared with the model group.Basso-Beattie-Bresnahan score in the endothelin-1 group was significantly decreased compared with the exosome group(P<0.05).Spinal cord injury was more severe in the endothelin-1 group than that in the exosome group.(2)The expression of endothelin-1 in the model group was significantly increased compared with the sham operation group(P<0.05),and the expression of endothelin-1 in the exosome group was significantly decreased compared with the model group(P<0.05).(3)The blood-spinal cord barrier Evans blue exudate in the exosome group was significantly decreased compared with the model group(P<0.05).The expression levels of the tight junction proteins β-Catenin,Occludin and ZO-1 in the exosome group were increased(P<0.05);the Evans blue exudate in the endothelin-1 group was significantly increased compared with the exosome group(P<0.05).The expression level of tight junction protein was significantly decreased compared with the exosome group(P<0.05).(4)The results show that human umbilical cord mesenchymal cell-derived exosomes protect the permeability of the blood-spinal cord barrier by down-regulating the expression of endothelin-1 and play a role in the repair of spinal cord injury.

A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Objective To investigate the predictive value of inflammatory cells and clinical features in the prognosis of immune checkpoint inhibitors (ICIs) treating non-small cell lung cancer (NSCLC).Methods The data of 163 cases of stage Ⅲ and Ⅳ NSCLC patients treated with the ICIs in this hospital from January 1,2017 to December 31,2022 were collected.The CT examination was conducted after 6-8 weeks treatment.The pa-tients were divided into the objective remission group[complete remission (CR)+partial remission (PR)]and non-objective remission group[stable disease (SD)+progressed disease (PD)],disease control group (CR+PR+SD) and non-disease control group (PD),persistent clinical benefit group (DCB) and non-DCB group.The differences in clinical features and inflammatory cells indicators were compared among the differ-ent groups.The receiver operating characteristic (ROC) curve was adopted to evaluate the predictive efficiency of the inflammatory cells indicators for DCB.The influencing factors analysis of progression free survival (PFS) time and overall survival (OS) time adopted the Cox regression analysis.Results The lymphocyte count (ALC) in the disease control group was higher than that in the non-disease control group.The neutro-phil to lymphocyte ratio (NLR),platelet-lymphocyte ratio (PLR) and mononuclear lymphocyte ratio (MLR) were lower than those in the non-disease control group.The proportions of squamous cell carcinoma,stage Ⅲ,ECOG score 0-1 point,adverse reactions in the DCB group were higher than those in the non-DCB group (P<0.05),the PLT count,NLR,PLR and MLR were lower than those in the non-DCB group (P<0.05). The ROC curve analysis results showed that PLT,NLR,PLR and MLR could serve as the indicators for pre-dicting DCB,the area under of ROC curve (AUC) was 0.633,0.602,0.635 and 0.604 respectively,the opti-mal cut off values were 187×109/L (P=0.004),5.0 (P=0.026),235 (P=0.003) and 0.35 (P=0.024) re-spectively.The multivariate Cox regression analysis showed that non-squamous carcinoma including adenocar-cinoma (HR=1.565,95％CI:1.057-2.316) and other pathologic types (HR=2.285,95％CI:1.326-3.936),ECOG score 2-3 points (HR=2.375,95％CI:1.652-3.415),AMC≥0.65×109/L (HR=1.847,95％CI:1.160-2.938) and PLR≥235 (HR=1.557,95％CI:1.016-2.386) were the independent risk factors for short PFS.The ECOG score 2-3 points (HR=4.615,95％CI:2.882-7.391),AMC≥0.65×109/L (HR=5.161,95％CI:2.984-8.925) and PLR ≥235 (HR=1.732,95％CI:1.059-2.833) were the independent risk fac-tors for short OS (P<0.05),and having adverse reactions (HR=0.472,95％CI:0.294-0.757) was the independ-ent protective factor for short OS (P<0.05).Conclusion Lower PLT,AMC,NLR,MLR and PLR,higher ALC,squamous cell carcinoma,TNM stage Ⅲ,ECOG score 0-1 point and immunotherapy related adverse reactions could prompt that the prognosis is good in ICIs treating advanced NSCLC.PLT,NLR,PLR and MLR could serve as the indicators for predicting DCB.

Objective:To investigate the surgical strategy for chronic pancreatitis complicated with suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas.Methods:This is a retrospective cohort study. Clinical data from 11 patients with chronic pancreatitis who underwent pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy(PD-L) were retrospectively collected(PD-L group) from the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi′an Jiaotong University between December 2021 and September 2023. All patients were male with an age of (49.0±11.2) years(range:32 to 70 years). Their primary preoperative diagnoses included pancreatic lesions, chronic pancreatitis, pancreatolithiasis, and dilatation of the pancreatic duct. Data from 248 patients who underwent pancreaticoduodenectomy(PD) during the same period were retrospectively collected(PD group). There were 157 males and 91 females in the PD group, with an age of (61.5±10.8) years(range:27 to 82 years). Among them, 87 cases were diagnosed as pancreatic cancer or chronic pancreatitis. The propensity score matching method was used to reduce confounding bias between the two groups. The caliper value of 0.1 was used and the 1∶4 nearest neighbor matching method was used for the matching. Comparisons between the two groups were made using the independent sample t test, Mann-Whitney U test or χ2 test,respectively. Results:After complete excision of the specimen during pancreaticoduodenectomy, the key surgical step of PD-L was longitudinal pancreaticojejunostomy in the remaining pancreas. Intraoperative blood loss in the PD-L group was lower than that in the PD group [ M(IQR)](300(200)ml vs. 500(500)ml, respectively; P<0.05). Similarly, hospitalization days(21.0(7.0)days vs. 25.0(8.5)days) and postoperative hospitalization days(13.0(8.0)days vs. 17.0(5.0) days) were also lower in the PD-L group compared to the PD group ( P<0.05). There were no significant differences in the operation time and postoperative complication rate between the two groups( P>0.05). In the PD-L group, the postoperative follow-up time was 5(5)months(range: 3 to 21 months). One case was lost for follow-up. Abdominal pain was relieved in 10 patients. Additionally, abdominal distension and steatosis were alleviated in 8 cases. Furthermore, 5 cases of diabetes mellitus showed improved control of HbA1c and fasting blood glucose levels after surgery. Conclusions:PD-L treatment can be used to treat chronic pancreatitis complicated by suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas. PD-L also has advantages in removing stones from the pancreatic duct and evaporation of pancreatic fluid. However, due to the single-center design and the small sample size of this study, further practice and long-term follow-up are still necessary.