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 association between cervical insufficiency(CI)and spontaneous preterm birth(SPB),and to investigate the predictive value of shear wave elastography(SWE),cervical length(CL),and anterior cervical angle(ACA)in identifying SPB resulting from CI.Methods This study recruited 786 pregnant women who attended prenatal outpatient clinics or were hospitalized for treatment at the Affiliated Hospital of Nantong University and the Maternity Hospital affiliated with Jiangnan University from June 2023 to January 2024.Among these participants,723 were full-term pregnancies and 63 were preterm pregnancies.Cervical SWEI,CL,and cervical ACA were measured using a Mindray Resona R9 Pro/Eagus R9s ultrasound device equipped with shear wave elasticity imaging software.Additionally,the participants were categorized into four gestational age groups:19-23+6 weeks,24-27+6 weeks,28-33+6 weeks,and 34-36+6 weeks,to evaluate the relationship between gestational age and ultrasound parameters.Results The mean CL in the preterm group was 25.4 mm,significantly shorter than the 29.7 mm observed in the full-term group(P<0.001).The ACA in the preterm group was 121°,which was significantly higher than the 99° in the full-term group(P<0.001).Additionally,SWE values were significantly lower in the preterm group compared to the full-term group at all measured cervical sites:anterior external os(AE)6.47 kPa versus 9.91 kPa(P<0.001),anterior internal os(AI)10.98 kPa versus 18.62 kPa(P<0.001),posterior internal os(PI)11.32 kPa versus 21.09 kPa(P<0.001),and posterior external os(PE)8.16 kPa versus 13.24 kPa(P<0.001).A significant negative correlation was found between CL and gestational age(r=-0.278,P=0.001).The combined predictive indicators demonstrated high accuracy and specificity for predicting preterm birth,with an area under the curve(AUC)of 0.952,sensitivity of 95%,and specificity of 86%.Conclusions The integration of cervical SWE,CL measurement,and assessment of the angle of ACA can substantially enhance the predictive accuracy for SPB due to CI.This multimodal approach offers clinicians a more robust and precise tool for identifying high-risk pregnancies,enabling timely interventions that can reduce the incidence of preterm birth and improve maternal and neonatal outcomes.

Objective:To compare the short-term clinical outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) in treating gastric cancer, as well as the overall 5-year's survival rate.Methods:In this retrospective cohort study, 874 patients undergoing minimally invasive gastrectomy were recruited from Jan 2016 to Jan 2020 (LG: n=719; RG: n=155). A one-to-one propensity score matching analysis was applied to minimize the selection bias due to confounding factors, yielding 150 patients in each of the RG and LG groups. After matching, the short-term outcomes and 5-year overall survival were compared in the two groups. Results:The propensity score matching cohort analysis showed a similar 5-year overall survival between RG and LG groups ( P=0.235). Concerning the short-term outcomes, the RG compared to LG resulted in lower blood loss ( P=0.011), lower postoperative complications ( P=0.001), less postoperative pain ( P=0.014), earlier initiation of soft diet ( P=0.010), shorter hospital stay ( P=0.011), but higher hospitalization expenses ( P=0.004). Conclusions:RG had a similar overall survival outcome compared to LG while offering better safety and efficacy in terms of less blood loss, lower surgery complications, faster recovery, and less postoperative pain. Higher hospital expenses were the main disadvantage of RG that could limit its application.

Objective To evaluate the association between cervical insufficiency(CI)and spontaneous preterm birth(SPB),and to investigate the predictive value of shear wave elastography(SWE),cervical length(CL),and anterior cervical angle(ACA)in identifying SPB resulting from CI.Methods This study recruited 786 pregnant women who attended prenatal outpatient clinics or were hospitalized for treatment at the Affiliated Hospital of Nantong University and the Maternity Hospital affiliated with Jiangnan University from June 2023 to January 2024.Among these participants,723 were full-term pregnancies and 63 were preterm pregnancies.Cervical SWEI,CL,and cervical ACA were measured using a Mindray Resona R9 Pro/Eagus R9s ultrasound device equipped with shear wave elasticity imaging software.Additionally,the participants were categorized into four gestational age groups:19-23+6 weeks,24-27+6 weeks,28-33+6 weeks,and 34-36+6 weeks,to evaluate the relationship between gestational age and ultrasound parameters.Results The mean CL in the preterm group was 25.4 mm,significantly shorter than the 29.7 mm observed in the full-term group(P<0.001).The ACA in the preterm group was 121°,which was significantly higher than the 99° in the full-term group(P<0.001).Additionally,SWE values were significantly lower in the preterm group compared to the full-term group at all measured cervical sites:anterior external os(AE)6.47 kPa versus 9.91 kPa(P<0.001),anterior internal os(AI)10.98 kPa versus 18.62 kPa(P<0.001),posterior internal os(PI)11.32 kPa versus 21.09 kPa(P<0.001),and posterior external os(PE)8.16 kPa versus 13.24 kPa(P<0.001).A significant negative correlation was found between CL and gestational age(r=-0.278,P=0.001).The combined predictive indicators demonstrated high accuracy and specificity for predicting preterm birth,with an area under the curve(AUC)of 0.952,sensitivity of 95%,and specificity of 86%.Conclusions The integration of cervical SWE,CL measurement,and assessment of the angle of ACA can substantially enhance the predictive accuracy for SPB due to CI.This multimodal approach offers clinicians a more robust and precise tool for identifying high-risk pregnancies,enabling timely interventions that can reduce the incidence of preterm birth and improve maternal and neonatal outcomes.

Objective:To compare the short-term clinical outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) in treating gastric cancer, as well as the overall 5-year's survival rate.Methods:In this retrospective cohort study, 874 patients undergoing minimally invasive gastrectomy were recruited from Jan 2016 to Jan 2020 (LG: n=719; RG: n=155). A one-to-one propensity score matching analysis was applied to minimize the selection bias due to confounding factors, yielding 150 patients in each of the RG and LG groups. After matching, the short-term outcomes and 5-year overall survival were compared in the two groups. Results:The propensity score matching cohort analysis showed a similar 5-year overall survival between RG and LG groups ( P=0.235). Concerning the short-term outcomes, the RG compared to LG resulted in lower blood loss ( P=0.011), lower postoperative complications ( P=0.001), less postoperative pain ( P=0.014), earlier initiation of soft diet ( P=0.010), shorter hospital stay ( P=0.011), but higher hospitalization expenses ( P=0.004). Conclusions:RG had a similar overall survival outcome compared to LG while offering better safety and efficacy in terms of less blood loss, lower surgery complications, faster recovery, and less postoperative pain. Higher hospital expenses were the main disadvantage of RG that could limit its application.

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.