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 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.

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.

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.

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 explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency.Methods:This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively.Results:The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 μmol/L) was found in all patients, and decreased to 20-70 μmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders.Conclusions:Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.

Objective:To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies.Methods:This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months.Results:Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work.Conclusions:Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

Objective To systematically evaluate the efficacy and safety of ciprofol for sedation and anesthesia outside the operating room.Methods Databases such as PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang Data,CBM,and VIP were searched for randomized controlled trials(RCTs)related to the efficacy and safety of ciprofol for sedation and anesthesia outside the operating room.The search covered all publications up to June 2023.Statistical analysis was performed using RevMan 5.4 software and Stata 15.0.Results Twelve RCTs were included,involving 2 192 patients,of which 1 154 were in the ciprofol group and 1 038 in the propofol group.Compared with the propofol group,the anesthesia induction time(MD=0.28 min,95％CI 0.08-0.47 min,P=0.006)and recovery time(MD=1.16 min,95％CI 0.44-1.87 min,P=0.001)were significantly longer in the ciprofol group,and the inci-dences of injection pain(OR=0.04,95％CI 0.02-0.06,P＜0.001),hypotension(OR=0.64,95％CI 0.49-0.83,P=0.0008),hypoxemia(OR=0.44,95％CI 0.21-0.91,P=0.03),and respirato-ry depression(OR=0.19,95％CI 0.11-0.32,P＜0.001)were significantly lower.There were no sta-tistically significant differences between the two groups in terms of sedation success rate,physician satisfac-tion,the difference in heart rate before and after anesthesia induction,incidence of body movement,brady-cardia,nausea and vomiting,and dizziness.Conclusion The anesthetic effect of cyclopofol and propofol is similar when used for anesthesia outside the operating room.Compared to propofol,ciprofol offers comparable anesthetic effects for sedation and anesthesia outside the operating room,with a lesser impact on respiratory function and more stable hemodynamics.Ciprofol also significantly lowers the incidence of adverse reactions such as injection pain,hypotension,hypoxemia,and respiratory depression.