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 investigate the clinical effect of surgical treatment of concealed penis based on the idea of flap transfer in the treatment of hypospadias.Methods:Retrospectively analyzed the clinical data of children with concealed penis admitted to the Urology Department of Chengdu Second People’s Hospital and Department of Pediatric Surgery at Children’s Medical Center of Sichuan Provincial People’s Hospital, from July 2017 to July 2021. The control group used the traditional surgical method and the experimental group used a modified surgical approach based on the idea of flap transfer in the treatment of hypospadias. Short-term complications such as flap ischemia, edema, and skin dehiscence were statistically analyzed in the two groups, as well as the Boemers rating of penile appearance (good, general, poor), Vancouver scar scale (VSS) (mild, moderate, severe), overall penis shape (tower, cylindrical, inverted tower) at 6 months after surgery. Count data were analyzed using the Chi-square test.Results:298 children, aged 2.5 to 13.7 years, with a mean age of 6.4 years, were enrolled in the study. 103 children were in the control group, and 195 children were in the experimental group. All enrolled patients were operated successfully in the first stage and were discharged 3-4 days after the operation, with an average recovery time of 3-4 weeks. After a follow-up of more than 6 months, in the control group, 2 cases (1.9%) of flap ischemia and 3 cases (2.9%) of skin dehiscence occurred after surgery. Two children (1.0%) in the experimental group had skin dehiscence after surgery, and the difference in the recent complication rate between the two groups was not significant [4.9%(5/103) vs. 1.0%(2/195), P>0.05]. The proportion of Boemers rated"good"in the experimental group was higher than that in the control group [93.3% (182/195) vs. 71.8% (74/103), P<0.01]. The proportion of moderate to severe scarring assessed by VSS was lower in the experimental group than in the control group [6.2% (12/195) vs. 26.2% (27/103), P<0.01]. The proportion of the overall penis shape of the penis close to the cylindrical shape of the normal penis in the experimental group was significantly higher than that in the control group [81.5% (159/195) vs. 60.2% (62/103), P<0.01]. Conclusion:Compared with the traditional surgical method, the modified surgical approach based on the idea of flap transfer in the treatment of hypospadias attaches more importance to the overall planning of the flap and the tension distribution of the fascial layer, which can be more effective to solve the problem of insufficient coverage of the concealed penile skin and reduce postoperative scar formation. Moreover, the appearance of the external genitalia is natural and closer to normal, the surgical effect is exact, and the long-term postoperative complications are lower.

Objective:To investigate the clinical effect of surgical treatment of concealed penis based on the idea of flap transfer in the treatment of hypospadias.Methods:Retrospectively analyzed the clinical data of children with concealed penis admitted to the Urology Department of Chengdu Second People’s Hospital and Department of Pediatric Surgery at Children’s Medical Center of Sichuan Provincial People’s Hospital, from July 2017 to July 2021. The control group used the traditional surgical method and the experimental group used a modified surgical approach based on the idea of flap transfer in the treatment of hypospadias. Short-term complications such as flap ischemia, edema, and skin dehiscence were statistically analyzed in the two groups, as well as the Boemers rating of penile appearance (good, general, poor), Vancouver scar scale (VSS) (mild, moderate, severe), overall penis shape (tower, cylindrical, inverted tower) at 6 months after surgery. Count data were analyzed using the Chi-square test.Results:298 children, aged 2.5 to 13.7 years, with a mean age of 6.4 years, were enrolled in the study. 103 children were in the control group, and 195 children were in the experimental group. All enrolled patients were operated successfully in the first stage and were discharged 3-4 days after the operation, with an average recovery time of 3-4 weeks. After a follow-up of more than 6 months, in the control group, 2 cases (1.9%) of flap ischemia and 3 cases (2.9%) of skin dehiscence occurred after surgery. Two children (1.0%) in the experimental group had skin dehiscence after surgery, and the difference in the recent complication rate between the two groups was not significant [4.9%(5/103) vs. 1.0%(2/195), P>0.05]. The proportion of Boemers rated"good"in the experimental group was higher than that in the control group [93.3% (182/195) vs. 71.8% (74/103), P<0.01]. The proportion of moderate to severe scarring assessed by VSS was lower in the experimental group than in the control group [6.2% (12/195) vs. 26.2% (27/103), P<0.01]. The proportion of the overall penis shape of the penis close to the cylindrical shape of the normal penis in the experimental group was significantly higher than that in the control group [81.5% (159/195) vs. 60.2% (62/103), P<0.01]. Conclusion:Compared with the traditional surgical method, the modified surgical approach based on the idea of flap transfer in the treatment of hypospadias attaches more importance to the overall planning of the flap and the tension distribution of the fascial layer, which can be more effective to solve the problem of insufficient coverage of the concealed penile skin and reduce postoperative scar formation. Moreover, the appearance of the external genitalia is natural and closer to normal, the surgical effect is exact, and the long-term postoperative complications are lower.

Objective:To investigate the therapeutic effect of exosomes divided from bone marrow mesenchymal stem cell (BMSC) on pancreatic cancer in vivo through regulation of tumor-associated macrophages (TAM) polarization.Methods:Ten male C57BL/6 mice weighing approximately 20 g, ages 4 weeks, were used for BMSC exosomes extraction and PKH26 labelling. Thirty female SPF BALB/c-nu/nu nude mice weighing approximately (18.56±0.85) g, ages 4-6 weeks, were adopted for pancreatic carcinoma models. The models were randomly divided into 3 groups with 10 in each: control group (injected with PBS through tail vein), portal vein treatment group (injected with exosomes in PBS through portal vein), tail vein treatment group (injected with exosomes in PBS through tail vein). After the models were executive 8 weeks later, the percentage of PKH26 positive-exosomes in pancreas tissue was quantified by flow cytometry technique. The volume of the primary pancreatic tumor, the tumor volume of inhibitory rate, the number of metastatic nodule, and the ascitic fluid were assess. Also, the weight of liver and the tumor weight were evaluated. The expression of M1 and M2 macrophage-activate biomarkers and the content of pancreatic cancer marker B7-H4 tumor carbohydrate antigen 199 in peripheral blood was detected. Moreover, the expression of Survivin and matrix metalloproteinase-9 (MMP-9) in pancreatic cancer tissue cells was also detected.Results:There was no significant difference for the tumor volume of inhibitory rate between portal vein treatment group (72.4±21.6)% and tail vein treatment group (70.1±20.7)% ( t=0.24, P=0.811). Compared with control group, the volume of the primary pancreatic tumor, the weight of liver, the tumor weight, the number and rate of liver metastatic nodule, the ascitic fluid, and the number of other metastatic nodule were totally lower in the 2 treatment groups with significant difference (all P<0.05). Compared with the control group, iNOS and CD68 in portal vein treatment group and tail vein treatment group were increased, while Arginase, CD206, B7-H4, tumor carbohydrate antigen 199, Survivin and matrix metalloprotein-9 were decreased, with statistically significant differences (all P<0.05). Conclusion:Exosomes derived from BMSC can inhibit the polarization of TAM to the M2 phenotype and induce their polarization to the M1 phenotype, thereby suppressing the proliferation, invasion and migration of pancreatic cancer.

Background: Psoriasis vulgaris is a chronic inflammatory skin disease which occur at any age. It can be clinically classified into two age-onset subtypes: early-onset psoriasis (EOP;＜40 years) and late-onset psoriasis (LOP; ≥40 years). More evidence showed EOP and LOP have different genetic architecture, notably the risk allele human leukocyte antigen (HLA)-C*06:02 located within the major histocompatibility complex (MHC) region, which was reported to be the outstanding variant associated with EOP. However, genetic structure of EOP and LOP have not been fully elucidated. Objective: To investigated HLA genetic heterogeneity between EOP and LOP in China. Methods: We first calculated the MHC-based heritability of EOP and LOP respectively.Then, we conducted a large-scale, stratified analysis including 7,097 EOP, 1,337 LOP patients, and 9,906 healthy controls by using MHC target sequencing data from a previousstudy. Results: We observed that HLA alleles collectively explained a larger heritability of EOP (27.4%) than LOP (11.3%).Further association analysis identified three independent loci (HLA-C*01:02, p=6.70×10−8 ; HLA-A amino acid position 9, p=3.27×10−17 ; and HLA-A amino acid position 161, p=5.75×10−10 ) that confer specific susceptibility to EOP. Our data also confirmed HLA-C*06:02 as an independent psoriasis-associated variant, contributing a higher degree of risk to EOP than LOP. Moreover, case-case analysis confirmed that HLA-C*06:02-positive psoriasis patients have earlier onset. Conclusion Our analysis indicating that different genetic background underlie the EOP and LOP. We believe these findings will serve to predict psoriasis risk in the future and facilitate clinical decision.

Objective:To conduct periodic revalidation of the 15 items and 43 terms autoverification rules of blood analysis after 1 year of application, analyze the application suitability and make the rules improved.Methods:Track the results of 528 010 blood analysis samples of our hospital from August 1, 2019 to January 31, 2020, and analyze the pass rate and interception rate of autoverification; 600 specimens in total were selected randomly for microscope examination, including 300 specimens which touched autoverification rules (1 012 items of autoverification rules) and were intercepted by autoverification and 300 specimens which untouched autoverification rules and were released by autoverification. The abnormal characteristics and unacceptable Delta check of the specimens also need to be concerned at the same time.The false negative rate and false positive rate, true negative rate, true positive rate and pass correct rate of autoverification were verified and compared with the rate of the second phase verification when the autoverification rule was established. The false negative rate, false positive rate, true negative rate and true positive rate of the Delta check rule which 54 716 specimens touched were calculated and compared with the second phase verification rate when the autoverification rule was established.The results of microscopic examination were used as the gold standard for the calculation of the rates, and P<0.05 was considered as a significant difference. The false positive and true positive of 1 012 autoverification rules were analyzed item by item.The false positive and true positive of 108 specimens which touched blast cell autoverification rule were analyzed terms by terms. The mean TAT and median TAT of 528 010 specimens and 193 750 outpatient specimens were calculated respectively, and the report percentages of 528 010 samples that TAT<30, 30-60　and>60 min were calculated respectively. Analyze and evaluate the application suitability of autoverification rules to juge whether they meet the needs of doctors and laboratory. The design process and the rules and application process of autoverification were optimized and improved.Results:The autoverification pass rate was 63.06% (332 971/528 010), the interception rate was 36.94% (195 039/528 010). The false negative rate was 1.00% (1/600), the false positive rate was 12.67% (76/600), the true negative rate was 49% (294/600), the true positive rate was 37.33% (224/600), and the correct rate was 98% (294/300). The pass rate, true negative rate, true positive rate and correct rate of the periodic reverification group were higher than the second phase verification group, the false negative rate and false positive rate were lower than that the second phase verification group. The false negative rate and true positive rate of the Delta check of periodic verification group were lower than that the second phase verification group, the false positive rate and true negative rate were higher than the second phase verification group, there were significant differences in the comparition results. The mean TAT of 528 010 specimens was25 min, and the median TAT was 22 min. The mean TAT of 193 750 outpatient specimens was 23 min, and the median TAT was 20 min. The report percentages of 528 010 samples that TAT<30 min, 30 min-60 min and>60 min were 83.30% (439 819/528 010), 8.00% (42 250/528 010) and 8.70% (45 941/528 010), respectively.Conclusion:The results of periodic revalidation of autoverification after 1 years application show that the 15 items and 43 terms autoverification rules of blood analysis could meet requirements about the accuracy and efficiency of the laboratory, and have a good suitability for application.

Objective To compare the postoperative effects of Onlay transverse island preputial flap and Onlay transverse free island preputial graft for midshaft hypospadias repair.Methods Retrospective analysis of clinical data of 59 patients with midshaft hypospadias who underwent hypospadias repair from January 2013 to December 2018.Among them,49 children were repaired with Onlay transverse island preputial flap,aged from 14 months to 81 months,with the median age of 28 months.Ten children were repaired with Onlay transverse free island preputial graft.The age at surgery was from 15 months to 51 months,with the median age of 30 months.There was no significant difference in term of the age at surgery between the two groups (Z =-0.384,P =0.701).There were 9 cases of Donnahoo Ⅱ and 40 cases of Donnahoo Ⅲ in the traditional Onaly group,and 3 cases of Donnahoo Ⅱ and 7 cases of Donnahoo Ⅲ in the free graft Onlay group,respectively.There was no significant difference in the type of chordee between the two groups(x2 =0.161,P =0.688).The classification of hypospadias,the length of the urethroplasty and surgical complications were compared.The maximum urinary flow rate of some patients was summarized and analyzed after operation.Results Follow-up ranged from 3 to 72 months,with a median period of 38 months.In the children who underwent Onlay transverse island preputial flap,there were 2 cases of distal shaft,5 cases of middle shaft,and 42 cases of proximal shaft.The neourethra was 1.3-3.5 cm,with a median of 2.3 cm.There were 11 cases of fistula,1 case of glan dehiscence,and 1 case of diverticulum.Ten children were treated with Onlay transverse free island preputial graft.There were 1 case of distal shaft,2 cases of middle shaft and 7 cases of proximal shaft.The neourethra was 1.2-2.5 cm,with a median of 2.0 cm.Two cases of fistula occurred after operation.There was no significant difference in hypospadias classification between the two groups(x2 =1.313,P =0.519).There was no significant difference in the length of the urethra between the two groups (Z =-1.732,P =0.083).There was no significant difference in the incidence of postoperative complications between the two surgical methods (x2 =0.001,P =0.973).The patients' parents were satisfied with the appearance of genital organ after operation.Fourteen patients finished the uroflowmetry 3 months after surgery.Twelve patients in the traditional Onlay group had a urine volume of 60.2-147.8 ml,with an average of 98.8 ml.The maximum urinary flow rate was 3.5-13.6 ml/s,with an average of 8.1 ml/s.In the free graft Onlay group,the urine volume was 101.3-165.4 ml,with an average of 133.5 ml,and the maximum urinary flow rate was 9.6-15.7 ml/s,with an average of 12.7 ml/s.Conclusions Onlay transverse free island preputial graft has the same complication incidence with Onlay transverse island preputial flap,but could get a good maximum urinary flow rate and cosmetic result,which could achieve a good choice for midshaft hypospadias repair.

Objective To identify Chinese character writing related cortex (WRC) and its relationship with hand motor cortical areas. Methods Ten native Chinese-speaking, right-hand volunteers were recruited in the study. NTMS mapping was conducted during picture naming task. The WRC were mapped based on nTMS-induced impairment of Chinese character writing. The extent and area of WRC was calculated. The right-hand motor representations were mapped while motor-evoked potentials were produced under nTMS stimulation. EMG data and coordinates of positive stimulus were recorded. The relationship between WRC and hand motor cortex (HMC) was analyzed on the basis of area comparison and distance calculation. Results The cortical areas related to Chinese character writing were mapped successfully in all subjects by nTMS. WRC was primarily centered in left posterior middle frontal gyrus (pMFG) (86%,55/64). The mean WRC area (161.03 mm2 ±62.58mm2) was significantly smaller than the mean HMC area (589.50 mm2±227.34mm2) (P<0.001). The WRC and HMC were not conjoined or overlapped in the dominant hemisphere. The distance between those two was 12.58mm±2.71mm. Conclusions NTMS can provide reliable assistance in mapping WRC areas. The WRC is relatively fixed and centralized in pMFG but is not overlapped with the HMC.

AIM To study the effects of No.1 Weiyan Decoction (Codonopsis Radix,Paeoniae Radix alba,Taraxaci Herba,etc.) on hypoxia and hypoxic tolerance in gastric mucosal epithelial cells in rats with precancerous lesion of gastric cancer (PLGC).METHODS Forty rats were randomly divided into normal,model,Vitacoenzyme Tablets and No.1 Weiyan Decoction groups.Except for the normal group,the rats in the other groups were given with N-methyl-N'-nitro-N-nitrosoguanidine and Little Chengqi Decoction to establish a PLGC rat model.Ten weeks after the administration,the gastric mucosal epithelial microvascular ultrastructure was observed,the expressions of Hif1a mRNA,HIF-1 α protein and VEGF protein in gastric mucosal epithelium were detected.RESULTS Compared with the normal group,the number of microvasculatures in gastric mucosal epithelium was decreased;lumen was severely stenosed or expansive;inner wall was not smooth and had adhesion;vascular endothelial cells were swollen;the expression of Hif1α mRNA showed an increasing trend;the expressions of HIF-1α protein and VEGF protein were anomalous in the model group.Compared with the model group,the gastric mucosal vascular lesion of PLGC rats was improved,and the expressions of Hif1a mRNA,HIF-1α protein and VEGF protein were significantly decreased in the No.1 Weiyan Decoction group.CONCLUSION No.1 Weiyan Decoction can improve hypoxia and hypoxia tolerance,and induce angiogenesis in gastric mucosal epithelium in PLGC rats.