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.

Objectives:To investigate the predictive factors of stroke associated-pneumonia (SAP) in patients with acute stroke, develop nomogram and neural network prediction models and verify their predictive performance.Methods:Patients with acute stroke admitted to the First Affiliated Hospital of Kunming Medical University and Zhenxiong County People's Hospital were included retrospectively. Multivariate logistic regression analysis was used to determine the independent predictive factors of SAP, and develop nomogram and neural network prediction models. Receiver operating characteristic curve (ROC) curves were used to validate and compare the predictive performances. Results:A total of 450 patients with acute stroke were enrolled, including 286 males (63.6%), aged 64.28±13.24 years; 344 patientss (76.4%) had ischemic stroke and 106 (23.6%) had hemorrhagic stroke; 128 patients (28.4%) experienced SAP. According to the random number method, they were divided into a modeling cohort ( n=300) and a validation cohort ( n=150). Multivariate logistic regression analysis in the modeling cohort showed that a higher baseline National Institutes of Health Stroke Scale (NIHSS) score, gastric tube placement, use of proton pump inhibitors, heart failure, and higher neutrophil/lymphocyte ratio (NLR) were the independent predictive factors of SAP. ROC curve analysis showed that the area under the ROC curve of the nomogram model for predicting SAP in the modeling cohort and validation cohort was 0.841 (95% confidence interval [ CI] 0.795-0.880) and 0.863 (95% CI 0.798-0.914), respectively. The sensitivity for predicting SAP were 75.00% and 70.45%, respectively, and the specificity was 81.94% and 92.45%, respectively. The area under the ROC curve of the neural network model for predicting SAP in the modeling cohort and validation cohort was 0.847 (95% CI 0.802-0.866) and 0.862 (95% CI 0.796-0.913), respectively. The sensitivity for predicting SAP were 76.19% and 72.73%, and the specificity was 79.17% and 89.62%, respectively. Conclusions:Higher NIHSS score, gastric tube placement, use of proton pump inhibitors, heart failure, and higher NLR are the independent risk factors for SAP in patients with acute stroke. The nomogram and neural network prediction model developed using the above risk factors have higher predictive value for SAP.

Objective:To observe the effect of stellate ganglion block(SGB)on serum inflammatory factors and the expression of α7nAChR protein in rats with acute peritonitis,so as to further explore the mechanism of SGB on the inflammatory response of acute peritonitis in rats.Methods:40 SPF grade male rats were randomly divided into 4 groups:blank group(Control),acute peritonitis group(AP),acute peritonitis+stellate ganglion block group(AP+SGB),acute peritonitis+stellate ganglion block+α7nAChR inhibitor methyllycaconitine group(AP+SGB+MLA),with 10 rats in each group.Inject 2％acetic acid at a dose of 1 ml/100 g into the peritoneal cavity of rats to establish an acute peritonitis model in the AP group,AP+SGB group,and AP+SGB+MLA group.Blood samples were collected from the tail vein of the rats,and the concentrations of IL-18 and TNF-α in serum were detected by ELISA.Western Blot method was used to detect the level of α7nAChR protein in the peritoneal tissues,and RT-qPCR method was used to detect the expression of α7nAChR mRNA in the peritoneal tissues.Results:Compared with Control group,the levels of IL-18 and TNF-α were increased in the other three groups(P＜0.05).Compared with AP group,serum levels of IL-18 and TNF-α in AP+SGB group were decreased(P＜0.05).Compared with AP+SGB group,serum levels of IL-18 and TNF-α were increased in AP+SGB+MLA group(P＜0.05).The expression of α7nAChR mRNA protein were higher in the three groups than group Control,(P＜0.05).Compared with AP group,α7nAChR protein and α7nAChR mRNA expression levels were higher in AP+SGB group and AP+SGB+MLA group(P＜0.05).Compared with AP+SGB group,α7nAChR protein and α7nAChR mRNA expression levels in AP+SGB+MLA group were lower(P＜0.05).Conclusion:Stellate ganglion block treatment can reduce the production of inflammatory factors and inhibit the inflammatory response of acute peritonitis in rats,and its anti-inflammatory mechanism may be related to the cholinergic anti-inflammatory pathway(CAP)mediated by α7nAChR.

Blau syndrome is a rare genetic disorder characterized by the a mix of granulomatous arthritis, uveitis, and dermatitis. Patients typically manifest multisystem involvement, including ocular, skin, and skeletal abnormalities. Blau syndrome is extremely rare, with a global incidence of less than one in a million among children. In this multidisciplinary consultation, we present a case of a 21-year-old young female patient having multisystemic involvement since early childhood. She was presented with multiple joint swelling, skin lesions, increased eye discharge, and accompanied by hypertension and arterial abnormalities, and received a diagnosis of uveitis. The patient had been receiving steroid treatment since the age of 6 and has tried various medications, with some improvement in joint swelling and ocular symptoms. Through this rare disease multidisciplinary consultation, we aim to provide guidance in the molecular diagnosis of the patient, multisystem assessment, and the selection and formulation of treatment plans. Additionally, we hope that by reporting this case, clinical physicians can gain a better understanding of the diagnosis and comprehensive treatment strategies for Blau syndrome, thereby improving the management and treatment of rare diseases.

Objective:To explore the feasibility and advantages and disadvantages of local anesthesia for TiRobot-assisted removal of sacroiliac screws by comparison with general anesthesia for TiRobot-assisted removal of sacroiliac screws.Methods:A retrospective study was performed in 39 patients with posterior pelvic ring fracture-dislocation who had undergone removal of percutaneous sacroiliac screws after fracture union from January 2017 to December 2020 at Department of Orthopaedic Surgery, Hospital Affiliated to Chengdu University. Their sacroiliac screws were removed with TiRobot assistance under local anesthesia (LA group) or general anesthesia (GA group). In the LA group of 18 cases, there were 10 males and 8 females, aged (43.3 ± 8.4) years (from 25 to 58 years); in the GA group of 21 cases, there were 12 males and 9 females, aged (44.9 ± 9.0) years (from 23 to 60 years). The 2 groups were compared in terms of time for planning screw removal path, fluoroscopy frequency, fluoroscopy time, operation time, anesthesia time, anesthesia cost, postoperative visual analogue scale (VAS) and postoperative ambulation time.Results:There was no statistically significant difference in baseline data between the 2 groups, showing comparability ( P>0.05). Follow-ups revealed grade A wound healing in all patients. There were no significant differences between the 2 groups in time for planning screw removal path, fluoroscopy frequency, fluoroscopy time or operation time ( P>0.05). The anesthesia time [(41.6 ± 8.3) min], anesthesia cost [(653.5 ± 102.6) yuan] and postoperative ambulation time [(2.6 ± 0.6) h] in the LA group were significantly less than those in the GA group [(52.3 ± 9.5) min, (2,475.6 ± 261.8) yuan and (8.7 ± 2.4) h] while the VAS score in the former group (3.8 ± 1.5) was significantly higher than that in the latter group (2.5 ± 1.3) (all P<0.05). Conclusions:It is feasible to use local anesthesia for TiRobot-assisted removal of sacroiliac screws. In TiRobot-assisted removal of sacroiliac screws, compared with general anesthesia, local anesthesia may lead to shorter anesthesia time, lower anesthesia cast and shorter ambulation time, but the patients need to be compliant enough.

Objective:To investigate the therapeutic efficacy and potential mechanisms of integrin α vβ 3-targeted radionuclide therapy (TRT) in combination with anti-programmed cell death protein ligand 1 (PD-L1) immunotherapy. Methods:Integrin α vβ 3-targeted molecule Arg-Gly-Asp (RGD) was conjugated with Evans blue (EB) and then labeled with 177Lu to obtain 177Lu-EB-RGD. The radioactivity and radiochemical purity were determined. MicroSPECT imaging, biodistribution, and in vivo therapeutic efficacy were subsequently performed in MC38 murine colon cancer models. Volume of tumor and body mass of mice were observed to assess the therapeutic efficacy and safety ( n=9 in each group). Flow cytometry was used to evaluate therapy response of saline-treated (control, group A), 18.5 MBq 177Lu-EB-RGD-treated (group B), 10 mg/kg PD-L1 antibody-treated (group C), TRT combined with immunotherapy-treated (group D, 18.5 MBq 177Lu-EB-RGD and 10 mg/kg PD-L1 antibody) mice and alterations in tumor microenvironment (PD-L1 + immune cells, CD8 + T cells and regulatory T cells). Independent-sample t test and repeated measures analysis of variance were used for data analysis. Results:The radioactivity of 177Lu-EB-RGD was (55.85±14.00) GBq/μmol. SPECT imaging clearly visualized the MC38 tumors in mice models with high uptake and long retention time, the tumor/muscle ratio reached 14.87±0.88 at 24 h postinjection, while less uptake and retention in normal tissues. Tumor uptake of 177Lu-EB-RGD was significantly higher than that of 177Lu-RGD 4 h post-injection ((12.00±1.60) vs (3.69±0.37) %ID/g; t=8.63, P<0.01). The efficacy results between each treatment group was significantly different ( F=7.32, P=0.03) at day 6 post-treatment. The combination therapy showed the most outstanding anti-tumor efficacy with 7/9 mice showed complete response. Flow cytometry results showed that TRT up-regulated the PD-L1 expression significantly, namely, PD-L1 + immune cells in group B and group A were significantly different (CD45 + /PD-L1: 2.34% vs 0.95%, CD11b + /PD-L1: 2.41% vs 0.66%; t values: 11.17 and 8.70, both P<0.01); immunotherapy and combination therapy dramatically stimulated the infiltration of CD8 + T cells (2.07% vs 0.26%, 2.71% vs 0.26%; t values: 4.10 and 6.03, both P<0.05). Conclusion:TRT in combination with immunotherapy synergistically enhance anti-tumor efficacy, which is expected to play a role in the treatment of patients with advanced tumor where TRT can be applied.

Objective To sum up and analyze the clinical and pathological characteristics in patients with both IgA nephropathy (IgAN) and diabetes mellitus. Methods A total of 500 patients were recruited, including 25 patients with both IgAN and diabetes mellitus, and 475 patients with IgAN only, who were diagnosed by renal-biopsy during Jan 2015 to Jan 2017 at the First Affiliated Hospital of Zhengzhou University. The clinical and pathological data were collected and analyzed using SPSS 22.0. Propensity Score Matching was used to match and select the patients in the both groups, and thereafter the depth of the basement membrane from the matched patients were compared using electron microscopy. The data of the patients whose follow - up time was ≥3 months were retrospectively collected, and Kaplan-Meier analysis was used to compare the difference of the prognosis. Results Compared to the patients with IgAN only, patients with both IgAN and diabetes mellitus were older [(46.36±13.49) years vs (34.00±13.80) years, P<0.001], had higher level of serum triglyceride [2.06(1.52, 3.11) mmol/L vs 1.51(1.01, 2.25) mmol/L, P=0.012] and thicker basement membrane [(384.33 ± 61.20) nm vs (346.72 ± 52.65) nm, P=0.044]. The patients with both IgAN and diabetes mellitus were more prone to reach the composite endpoint [4/7(57.14％) vs 25/265(9.33％), P<0.001] and had worse prognosis (Log-Rank test, P=0.004). Conclusions IgAN patients with diabetes mellitus have different clinical, pathological characteristics and prognosis from patients with IgAN alone. These patients need to be closely monitored and actively treated.

Objective To introduce an integral classification method of thoracic deformity. Methods From March 2015 to March 2017, 869 patients with thoracic deformity were observed. The patients were classified according to the traditional classification method at first, and then were classified according to the integral classification method. According to the standard plane of the normal chest wall, the chest deformities were classified into types Ⅰ and Ⅱ: those below the plane belonged to type Ⅰ, and those above the plane belonged to type Ⅱ. Then two types were divided into subtypes Ⅰ-a, Ⅰ-b, Ⅰ-c, Ⅰ-d, Ⅰ-e, Ⅰ-f, Ⅰ-g and Ⅱ-a, Ⅱ-b, Ⅱ-c, Ⅱ-d according to the specific characteristics of malformation. Results There were 840 patients included in the classification system, accounting for 96.7% of the total patients, and the remaining 29 (3.3%) were complicated malformations, which could not be accurately described by using a single classification type. Compared with the traditional classification methods, patients with pectus excavatum and pectus carinatum were divided into different subtypes. Poland syndrome did not exist any longer, and Dove chest alone became the type Ⅱ-c. Conclusion Integral classification method is a simple and practical classification method. Since the method directly depends on the characteristics of malformation which is related to the operation, it plays a guiding role in the operation. But its superiority needs to be further confirmed.

Objective To introduce a novel classification method for pectus excavatum. Methods A retrospective review of 569 operative patients with pectus excavatum between January 2015 and September 2017 in our hospital was performed. The malformations were described and classified from three dimensions: symmetry (abbreviated as S), depth (abbreviated as D) and position (abbreviated as P). The final integral was calculated according to the deformity index, so that the severity of the deformity could be evaluated. All patients underwent Nuss or modified Nuss surgery. Results All pectus excavatum deformities were classified into 24 types. The most common type was S1D2P1, accounting for 27.2% of the total patients followed by S1D2P2, S1D1P2 and S2D2P2, accounting for 12.0%, 11.6% and 11.4% of all patients respectively. S1D3P3, S1D3P4 and S2D3P3 were not found in our patients. According to the integral, 321 patients were mild, 23 severe, and the rest were moderate. The appearance of all patients improved after the operation. Among them, 405 patients were implanted with a plate, 159 with two plates and 5 with three plates. The length of hospital stay was 5-12 d, with an average of 7.3±1.5 d. Conclusion This classification method is a more comprehensive classification, but its scientific and practical characteristics need to be further confirmed.

Objective To observe the changes of invasion and migration patterns and integrin expression of malignant glioma cells when Rac and Rho pathways are suppressed,respectively,in 3D hydrogel.Methods Liposome mediated pCMVLifeAct-TagGFP2 plasmids were transfected into glioma U87 cells,and then,these cells were divided into NSC23766 treatment group,Y-27632 treatment group,NSC23766 and Y-27632 combined treatment group,and control group.The three treatment groups were added NSC23766 (100 nmol/mL),Y-27632 (10 nmol/mL),100 nmol/mL NSC23766 and 10 nmol/mL Y-27632,respectively;the cells in the control group were added the same amount of medium.Cells were cultured in hydrogel;the composition of round cells,spindle cells and the mesenchymal and amoeboid cell movement transition were observed under confocal microscopy.The hydrogels of each group were infused into the microslide,and the cell chemotaxis effect were recorded and the cell movement velocities and distances were calculated in the living cell workstation.Immunofluorescence was used to observe the alternation ofintegrin expression.Results U87 cells cultured in 3D hydrogel exhibited spindle-like and round-like shapes,corresponding to mesenchymal and amoeboid cell movement.As compared with that in the control group,the proportion of round cells in the NSC23766 treatment group was significantly higher,and that of spindle cells in the Y-27632 treatment group was significantly higher (P＜0.05).The conversion rate ofmesenchymal-amoeboid transition was 50.0％ in NSC23766 treatment group and amoeboid mesenchymal transition was 42.8％ in Y-27632 treatment group as compared with that in the control group,with significant differences (P＜0.05).The velocity and distance of cells cultured in 3D hydrogel decreased orderly in NSC23766 treatment group,control group,Y-27632 treatment group and combined treatment group in chemotaxis test.The immunofluorescence test showed that integrin expression in the Y-27632 treatment group was significantly higher than that in the other three groups,and that in the control group was statistically higher than that in the NSC23766 treatment group and combined treatment group (P＜0.05).Conclusions 3D hydrogel can be used as a favorable substrate for cell culture.The combination targeted inhabitation of Rac 1 and RohA pathways provides theoretical basis for anti-invasion treatment against glioma.