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.

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

Objective To evaluate the clinical efficacy of Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate plus traditional Chinese medicine(TCM)bone-setting manipulations for the treatment of moderate hallux valgus.Methods A retrospective study was conducted.A total of 49 patients(62 feet)with moderate hallux valgus were treated with Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate,and were given TCM bone-setting manipulations before the operation,during the operation,and after the operation.The efficacy was evaluated by using the Visual Analogue Scale(VAS)score and the American Orthopedic Foot and Ankle Society(AOFAS)forefoot score after the operation.Before the operation and 12 months after the operation,the hallux valgus angle(HVA),intermetatarsal angle(IMA)between the first and second metatarsal bone,and the distal metatarsal articular angle(DMAA)showed by X-ray imaging in the weight-bearing position of the foot were recorded.Results(1)All of the 49 patients were followed up for 12 to 24 months,with a mean of(20.6±3.1)months.(2)The X-ray imaging assessment showed that 12 months after the operation,the mean HVA,IMA and DMAA values of the 49 patients(62 feet)were significantly lower than those before the operation,and the differences were all statistically significant(P＜0.01).(3)Twelve months after the operation,the pain VAS score of 49 patients was(3.14±1.21)points,which was significantly lower than the preoperative score points(7.26±2.52),and the difference was statistically significant(P＜0.01).(4)The assessment of joint function showed that 12 months after the operation,the scores of various AOFAS items of pain,function and hallux alignment as well as the overall AOFAS scores of 49 patients were significantly higher than those before the operation,and the differences were statistically significant(P＜0.01).(5)For the 62 feet in 49 patients,the excellent efficacy was achieved in 53 feet,good efficacy was achieved in 7 feet,and fair efficacy was achieved in 2 feet,with the fine rate of 96.77%(60/62).Conclusion For the treatment of moderate hallux valgus,the application of Chevron minimally-invasive osteotomy and internal fixation with ISO intramedullary plate plus TCM bone-setting manipulations is effective on promoting the reset of hallux-metatarsophalangeal joint,restoring the balance of the joint,and maintaining the equilibrium state of the joint through postoperative rehabilitation guidance.The combined therapy exerts certain efficacy,reduces the recurrence rate,and eventually achieves the early rehabilitation after the operation.

An analytical method based on ultra high performance liquid chromatography-high resolution tandem mass spectrometry(UHPLC-HRMS/MS)and high performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-TQ MS)was established to reveal the characteristics of various sulfur mustard analogs with different active thiol molecules in CWC Schedule 1.A.04.Firstly,the toxic agents were prepared by micro-directed synthesis,and then the differences of the reactivity and abundance of formed adducts between different sulfur mustards and glutathione(GSH),cysteine(Cys)and N-acetylcysteine(NAC)in incubation solution,plasma and cell were investigated,respectively.The results indicated that all target sulfur mustards could react with three kinds of thiol molecules.The content of Cys and sulfur mustard adducts in plasma was higher than that of GSH and sulfur mustard adducts,while NAC and sulfur mustard adducts might have fewer types of adducts due to low content or poor mass spectrometry response.Additionally,the content of GSH and sulfur mustard adducts in exposed cells was higher than that of Cys,which should be due to the significant difference in the content of thiol molecules in plasma and cells.

Objective To investigate the relationship between coronary artery plaque AI quantitative parameter and FFR-CT in coronary computed tomography angiography.Methods A total of 84 patients suspected of having CAD[52 males and 32 females,aged 27 to 81 years with a mean age of(58.1±11.9)years]were enrolled in this study.All patients underwent coronary computed tomography angiography.The CCTA data was processed using shukun(SK)software for labeling and analysis of the coronary arteries,as well as obtaining quantitative parameters of coronary artery plaque AI and corresponding FFR-CT values.The quantitative parameters included plaque length,total volume,minimum lumen area(MLA),minimal lumen degree(MLD),lipid composition volume and proportion,fibrous-lipid composition volume and proportion,fibrous composition volume and proportion,calcified composition volume and proportion.Coronary artery hemodynamic abnormality or myocardial ischemia was defined as an FFR-CT value≤0.8.Correlational analysis was performed to evaluate the association between AI plaque quantitative param-eters and FFR-CT values.Univariate and multivariate binary logistic regression analyses were conducted to identify independent risk factors for predicting FFR-CT≤0.8.The predictive performance of the model based on AI plaque quantitative parameters was assessed using receiver operating characteristic(ROC)curve analysis and calculation of the area under the curve(AUC).Sensitivities,specificities,diagnostic test accuracy rates were also calculated.Results The predominant symptoms observed in the cohort of 84 patients were chest pain(n=39,46.4%)and distress(n=27,32.1%).Spearman analysis results revealed a weak positive correlation between FFR-CT and MLA(r=0.49,P<0.0001),while weak negative correlations were found for plaque length,total volume,lipid composition volume,fibrous-lipid composition volume,fibrous composition volume,and calcified composition volume(r=-0.44,-0.56,-0.40,-0.36,-0.42,-0.40;all P<0.05).Additionally,MLD exhibited a moderate negative correlation with FFR-CT(r=-0.60,P<0.0001).In the univariate binary logistic regression analysis,several variables including plaque length,total volume,MLA,MLD,lipid composition volume,fibrous-lipid composition volume,fibrous composition volume,and calcified composition volume were found to be independently associated with FFR-CT≤0.8(All P<0.05).The adjusted multivariate binary logistic regression analysis model revealed that MLD was the sole independent predictor(OR=1.082,95%CI:1.034～1.133,P=0.001).The logistics re-gression model expression was logit(P)=0.079X1-4.052,where X1 represents the value of MLD and achieved a predictive accuracy of 85.2%.The ROC AUC of plaque length,total volume,MLA,MLD,lipid composition vol-ume,fibrous-lipid composition volume,fibrous composition volume and calcified composition volume were 0.796,0.886,0.711,0.754 and 0.698 respectively,and the coresponding sensitivities and specificities were 47.83%,73.91%,73.90%,52.17%,60.87%and 92.11%,73.68%,60.53%,84.21%,89.47%.The five in-dexes combined diagnostic model possessed the largest AUC of 0.906,and 73.91%,71.05%of sensitivity and specificity.Conclusion The AI quantitative parameters of coronary artery plaque exhibited varying degrees of correlation with FFR-CT,while MLD emerged as the sole independent predictor of FFR-CT≤0.8,demonstrating high diagnostic efficiency.

OBJECTIVES: To diagnose coronary artery stenosis by using the postmortem computed tomography angiography (PMCTA), and to explore the diagnostic value of PMCTA in sudden cardiac death. METHODS: Six death cases were selected, and the contrast medium iohexol was injected under high pressure through femoral artery approach with 5F pigtail catheter to obtain coronary image data and then the data was analyzed. The results of targeted coronary imaging and coronary artery calcium score (CaS) were compared with the results of conventional autopsy and histopathological examination. RESULTS: The autopsy and histopathological examination of cases with coronary artery stenosis obtained similar results in targeted coronary angiography, with a diagnostic concordance rate of 83.3%. Targeted coronary angiography could effectively show coronary artery diseases, and the CaS was consistent with the results of conventional autopsy and histopathological examination. CONCLUSIONS Targeted coronary angiography can be used as an effective auxiliary method for conventional autopsy in cases of sudden cardiac death.
Humans ; Computed Tomography Angiography/methods* ; Coronary Angiography/methods* ; Coronary Artery Disease/diagnostic imaging* ; Coronary Stenosis/diagnostic imaging* ; Death, Sudden, Cardiac/pathology*

OBJECTIVE: To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML). METHODS: The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m² /d×3 d). RESULTS: Among the 93 patients, 63 males and 30 females, were diagnosed as MDS（n ＝77）, MDS-AML（n ＝16）. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease（aGVHD） and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease（cGVHD） and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS（P =0.008）and DFS (P =0.019). CONCLUSION Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.
Male ; Female ; Humans ; Decitabine ; Retrospective Studies ; Transplantation, Homologous/adverse effects* ; Transplantation Conditioning/adverse effects* ; Myelodysplastic Syndromes/complications* ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Chronic Disease ; Graft vs Host Disease/therapy* ; Recurrence

Rats ; Animals ; RNA, Long Noncoding/genetics* ; RNA, Messenger/genetics* ; Microwaves ; Transcriptome ; Hippocampus

OBJECTIVE: To explore the cause for the failure of non-invasive prenatal testing (NIPT) and feasibility of repeated testing. METHODS: Clinical data, test results and pregnancy outcomes of 40 311 pregnant women who received NIPT test from January 2011 to December 2018 were reviewed. RESULTS: Among all the pregnant women, 1116 cases failed in the first test, 9 cases (0.81%) had fetal free DNA concentration lower than 4%, 663 cases (59.41%) were retested after the establishment of Z value gray area, and the remainder 444 cases (39.78%) needed to be retested after the blood collection due to the fetal free DNA concentration lower than 4%. After retesting, 1069 cases (95.78%) obtained effective NIPT results. The results showed that 53 cases were at high risk (6 cases for trisomy 21, 6 cases for trisomy 18, 13 cases for trisomy 13, 16 cases for sex chromosomal abnormality, 12 cases for chromosomal copy number variation). Forty-eight cases were selected for invasive prenatal diagnosis, and 2 cases of 47, XXY and 2 CNV were confirmed. A total of 47 cases (0.12%) did not obtain results because the concentration of fetal free DNA was lower than 4%. Only 16 cases (34%) chose invasive prenatal diagnosis. CONCLUSION Repeated detection of the gray area of Z value can reduce the false positive rate of NIPT and invasive prenatal diagnosis, and the feasibility of repeated detection is high. In the case of fetal free DNA concentration lower than 4%, the success rate of obtaining effective NIPT results by re-sampling and re-detection increases with the increase of gestational age, but may delay the diagnosis for fetal aneuploidies. Therefore, personalized estimation should be made according to gestational age and clinical indications. It is suggested that pregnant women should choose invasive prenatal diagnosis when they have failed in the retest.

Objective To investigate the expression of long non－coding ＲNA SFTA1P in non small cell lung cancer ( NSCLC) and its biological function in NSCLC cell lines． Methods Quantitative real time polymerase chain reaction( qＲT－PCＲ) was used to detect the expression of SFTA1P in 18 pairs of NSCLC tissues and adjacent normal tissues． The expression of SFTA1P was detected by qＲT－PCＲ in five different NSCLC cell lines ( A549，SPCA1，H460，H1975 and H1299) and one normal lung epithelial cell line ( HBE) ． The overexpression vector of SFTA1P was designed and constructed． The overex- pressed cell line was constructed by transfection，the effects of overexpression of SFTA1P on proliferation， invasion and migration of NSCLC cells were detected by CCK－8 assay and transwell assay． Ｒesults The expression of SFTA1P in NSCLC tissues was lower than that of adjacent normal tissues ( t = 2. 158，P = 0. 043) ． SFTA1P expression was detected in 5 strains of NSCLC cell lines and normal lung epithelial cell line． The expression of SFTA1P was the lowest in A549 and H460 cell lines ( t = 5. 769，P = 0. 004; t = 5. 772，P= 0. 004) ，and the highest in H1299 and H1975 cell lines ( t = 22. 248，P＜0. 001; t = 11. 814，P ＜0. 001) ． SFTA1P overexpression cell models were successfully constructed using A549 and H460 cell lines( all P＜0．05) ． The overexpression of SFTA1P could inhibit proliferation，invasion and migration of H460 and A549 cells ( ( all P ＜ 0． 05) ． Conclusions SFTA1P can affect the biological functions of NSCLC cells by inhibiting the proliferation，migration and invasion． SFTA1P may play a role as a tumor suppressor gene in tumorigenesis and development．