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 develop a predictive model for postoperative mortality risk in patients with acute aortic dissection(AAD)using the Extreme Gradient Boosting(XGBoost)algorithm combined with Shapley Additive Explanation(SHAP),and to establish a prediction website to serve as a diagnostic and therapeutic support platform for clinicians and patients.Methods A retrospective cohort study design was adopted.Data from 782 AAD patients who underwent surgical treatment at the Fourth Hospital of Hebei Medical University from January 2013 to December 2023 were collected,including basic information and initial serum biomarker test results.Patients were randomly divided into training and test sets at a 7:3 ratio.An external validation set consisting of 313 AAD patients admitted to the Second Hospital of Hebei Medical University from January 2020 to December 2023 was also established for further model validation.Variables were screened using LASSO regression,and an XGBoost machine learning model was constructed and interpreted using SHAP.The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curve analysis.Using the Shiny package,the XGBoost model was deployed to shinyapps.io to create a prediction website for postoperative mortality risk in AAD patients.One patient was selected by simple random sampling from the test set and the external validation set respectively for the prediction example on the Shiny webpage.Results The XGBoost model demonstrated high predictive performance for postoperative mortality in AAD patients,with area under the ROC curve(AUC)values of 0.928(95%CI 0.901-0.956)in the training set,0.919(95%CI 0.891-0.949)in the test set,and 0.941(95%CI 0.915-0.967)in the external validation set.SHAP values indicated the following order of variable importance in the model(from highest to lowest):"lactate dehydrogenase""blood chlorine""multiple organ injury""carbon dioxide combining power""prothrombin time""α-hydroxybutyric acid""creatine kinase isoenzyme""Stanford classification""combined use of bedside blood purification""gender""acute kidney injury""gastrointestinal bleeding""brain injury"and"shock".A risk prediction website for adverse postoperative outcomes in AAD patients was developed using XGBoost-SHAP method(https://dun-dunxiaolu.shinyapps.io/document/)and validated with examples.One randomly selected patient from each of the test and external validation sets was applied:the predicted mortality risk value for patient 1(who died postoperatively)was 0.9539,and that for patient 2(who survived postoperatively)was 0.0206.Conclusions The XGBoost-SHAP model demonstrates high accuracy in predicting postoperative mortality risk for AAD patients.The online prediction tool established based on this model enhances the identification efficiency of high-risk postoperative mortality patients.

Objective To report a case of tibial synovial sarcoma and review relevant literature to enhance understanding of this disease.Methods The clinical data of a patient with tibial synovial sarcoma treated at Kaifeng Central Hospital were retrospectively analyzed.A literature search was conducted in domestic and international databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,PubMed,Web of Science,and Embase,up to July 2024.Relevant literature was comprehensively reviewed to summarize the imaging and pathological characteristics,treatment,and prognosis of synovial sarcoma.Results A 29-year-old female patient was admitted with left lower extremity pain.X-ray examination revealed a proximal tibia space-occupying lesion suggestive of malignancy,and a mid-tibial space-occupying lesion considered benign.Contrast-enhanced computed tomography(CT)and plain magnetic resonance imaging(MRI)of the proximal tibial lesion also suggested malignancy.Ultrasound-guided biopsy of the proximal tibial tumor revealed a poorly differentiated malignant tumor.Immunohistochemistry results indicated monophasic synovial sarcoma,requiring genetic testing for definitive diagnosis.The patient underwent wide resection of the proximal left tibial malignancy with tumor-type artificial joint replacement,combined with curettage and bone cement filling for the left mid-tibial lesion under anesthesia.Postoperative pathology of space-occupying lesions in the proximal tibia confirmed monophasic synovial sarcoma,and fluorescence in situ hybridization(FISH)demonstrated a rupture of the synovial sarcoma translocation gene(SYT)(i.e.,SS18 positive).There was no recurrence or metastasis found in the patient during the reexamination 6 months after postoperative chemotherapy.As of July 2024,15 cases of genetically confirmed primary intraosseous synovial sarcoma have been reported internationally.Symptoms included pain and swelling,with a medical history of 1-2 years.The X-ray and CT findings showed osteolytic destruction with bone cortical discontinuity.In 13 cases,the intraosseous masses extended to the extraosseous area;in 2 cases,punctate calcifications were detected within the masses.Plain MRI scan showed iso-signal or hypo-signal on T1WI and hyper-signal,iso-signal,and hypo-signal on fat-suppressed T2WI,and enhanced MRI scan demonstrated heterogeneous enhancement.Pathological examination showed spindle-shaped cells under microscopy.Immunohistochemistry results showed positive epithelial membrane antigen(EMA),broad-spectrum cytokeratin(AE1/AE3),Ewing's sarcoma marker(CD99),and transducin-like enhancer of Split 1(TLE1).Twelve patients underwent surgical treatment;6 patients received adjuvant chemotherapy after surgery,of whom 4 developed local recurrence or distant metastasis at initial diagnosis,and 3 died during follow-up.Among the 6 patients who did not receive adjuvant chemotherapy,3 suffered from recurrence or distant metastasis.Conclusions Primary intraosseous synovial sarcoma is a rare malignant tumor with non-specific clinical manifestations.Imaging features typically include osteolytic destruction and intraosseous masses extending extraosseously,suggesting an intraosseous origin.Pathology and immunohistochemistry aid diagnosis,but definitive confirmation relies on further genetic testing.At present,the main treatment regimens for synovial sarcoma involve comprehensive therapies such as surgery and adjuvant chemotherapy,and the prognosis of patients is poor.

Objective:To investigate the surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment.Methods:The retrospective cohort study was conducted. The clinicopathological data of 91 patients with hilar cholangiocarcinoma who underwent surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from April 2004 to April 2021 were collected. There were 59 males and 32 females, aged (61±10)years. Patients who were admitted from April 2004 to March 2014 underwent traditional surgical diagnosis and treatment, and patients who were admitted from April 2014 to April 2021 underwent multidisciplinary diagnosis and treatment. Observation indica-tors: (1) surgical situations; (2) postoperative situations; (3) postoperative pathological examina-tions; (4) postoperative prognosis analysis; (5) influencing factors of postoperative prognosis. Follow-up was conducted using telephone interview and outpatient examination. Patients were followed up once every 6 months after surgery to detect survival. The follow-up was up to April 2023. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and calculate survival rate. The Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard model. Results:(1) Surgical situations. Of the 91 patients, there were 65 cases receiving hemi- or expanded hemi-hepatectomy, 13 cases receiving tri-hepatectomy, 9 cases receiving partial hepatectomy, 4 cases receiving extrahepatic bile duct resection. There were 24 cases receiving combined vein resection and reconstruction, 8 cases receiving combined pancreaticoduodenectomy, 6 cases receiving com-bined hepatic artery resection and reconstruction, including 24 cases receiving extended radical surgery (tri-hepatectomy, hepatic artery resection and reconstruction, hepatopancreaticoduodenec-tomy). The operation time, volume of intraoperative blood loss and intraoperative blood transfusion rate of 91 patients was (590±124)minutes, 800(range, 500?1 200)mL and 75.8%(69/91), respectively. Of the 91 patients, cases receiving extended radical surgery, the volume of intraoperative blood loss were 4, 650(range, 300?1 000)mL in the 31 patients who were admitted from April 2004 to March 2014, versus 20, 875 (range, 500?1 375)mL in the 60 patients who were admitted from April 2014 to April 2021, showing significant differences between them ( χ2=4.39, Z=0.31, P<0.05). (2) Post-operative situations. The postoperative duration of hospital stay and cases with postoperative infectious complications were (27±17)days and 50 in the 91 patients. Cases with abdominal infection, cases with infection of incision, cases with bacteremia and cases with pulmonary infection were 43, 7, 5, 8 in the 91 patients. One patient might have multiple infectious complications. Cases with bile leakage, cases with delayed gastric emptying, cases with chylous leakage, cases with liver failure, cases with pancreatic fistula, cases with intraperitoneal hemorrhage, cases with reoperation, cases dead during the postoperative 90 days were 30, 9, 9, 6, 5, 3, 6, 3 in the 91 patients. Cases with abdominal infection was 10 in the 31 patients who were admitted from April 2004 to March 2014, versus 33 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=4.24, P<0.05). Cases dead during the postoperative 90 days was 3 in the 31 patients who were admitted from April 2004 to March 2014, versus 0 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( P<0.05). (3) Post-operative pathological examinations. Of the 91 patients, cases with Bismuth type as type Ⅰ?Ⅱ, type Ⅲ, type Ⅳ, cases with T staging as Tis stage, T1 stage, T2a?2b stage, T3 stage, T4 stage, cases with N staging as N0 stage, N1 stage, N2 stage, cases with M staging as M0 stage, M1 stage, cases with TNM staging as 0 stage, Ⅰ stage, Ⅱ stage, Ⅲ stage, ⅣA stage, ⅣB stage, cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 46, 30, 1, 9, 25, 30, 26, 49, 36, 6, 85, 6, 1, 7, 13, 58, 6, 6, 63, 28. Cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 16 in the 31 patients who were admitted from April 2004 to March 2014, versus 48, 12 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=9.59, P<0.05). (4) Postoperative prognosis analysis. Of the 91 patients, 3 cases who died within 90 days after surgery were excluded, and the 5-year overall survival rate and median overall survival time of the rest of 88 cases were 44.7% and 55 months. The 5-year overall survival rate was 33.5% in the 28 patients who were admitted from April 2004 to March 2014, versus 50.4% in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=5.31, P<0.05). Results of further analysis showed that the corresponding 5-year overall survival rate of cases without lymph node metastasis was 43.8% in the 16 patients who were admitted from April 2004 to March 2014, versus 61.6% in the 31 patients who were admitted from April 2014 to April 2021. There was a significant difference in the 5-year overall survival rate between these patients without lymph node metastasis ( χ2=3.98, P<0.05). The corresponding 5-year overall survival rate of cases with lymph node metastasis was 18.5% in the 12 patients who were admitted from April 2004 to March 2014, versus 37.7% in the 29 patients who were admitted from April 2014 to April 2021. There was no significant difference in the 5-year overall survival rate between these patients with lymph node metastasis ( χ2=2.25, P>0.05). (5) Influencing factors of postoperative prognosis. Results of multivariate analysis showed that poorly differentiated tumor and R 1 or R 2 resection were inde-pendent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma ( hazard ratio=2.62, 2.71, 95% confidence interval as 1.30?5.29, 1.30?5.69, P<0.05). Conclusions:Compared with traditional surgical diagnosis and treatment, treatment of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment can expand surgical indications, reduce proportion of dead patients within 90 days after surgery, improve proportation of radical resection and long-term survival rate. Poorly differentiated tumor and R 1 or R 2 resection are independent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma.

Objective: To analyze the epidemiological characteristics and influencing factors of COVID-19 confirmed cases with viral nucleic acid re-positive in anal and/or throat swabs after discharge during the domestic imported epidemic stage in Guangdong Province in early 2020. Methods: The COVID-19 confirmed cases with the onset time before March 1, 2020 in Guangdong Province were collected to analyze the demographic data, epidemiological characteristics, and specimen collection and testing data after discharge. Logistic regression model was used for influencing factors analysis of re-positive cases. Results: A total of 1 286 COVID-19 confirmed cases were included, the M(Q₁,Q₃) of age was 44(32,58)years, 617 cases were male, 224 cases were re-positive in anal and/or throat swabs with the re-positive rate 17.42%. The M(Q₁,Q₃) of age of re-positive cases was 35(23, 50) years, which was younger than that of re-negative cases age was those 46(33, 59) years (P<0.001). With the increase of age, re-positive rate decreased (χ²_trend=52.73, P<0.001). 85.27% (191/224) of re-positive cases were found in 14 d after discharge, the duration time of re-positive status was 13(7, 24) d, and 81.69% (183/224) of re-positive cases were re-tested negative in 28 d after re-positive date. No fever and other symptoms had been observed among re-positive cases during the whole follow-up. No secondary infectious cases had been found among close contacts after 14 d of centralized isolation and sampling screening. Univariate logistic regression model analysis revealed that the influencing factors of the re-positive cases included age, occupation, clusters, clinical types, and admission time. Multivariate logistic regression model analysis revealed that age was an independent risk factor. Conclusions: SARS-CoV-2 viral nucleic acid re-positive is found in COVID-19 confirmed cases after discharge in Guangdong Province. Most re-positive cases are confirmed among 14 d after discharge and re-test to negative among 28 d after re-positive date. Age is an risk factor for re-positive cases after discharge.
COVID-19 ; China/epidemiology* ; Epidemics ; Humans ; Male ; Nucleic Acids ; SARS-CoV-2

Adult ; Echinococcosis/surgery* ; Echinococcosis, Hepatic/surgery* ; Feasibility Studies ; Female ; Hepatectomy ; Humans ; Kidney Diseases/surgery* ; Liver Diseases/surgery* ; Male ; Middle Aged ; Nephrectomy ; Pneumonectomy ; Retrospective Studies ; Treatment Outcome

Objective:To explore the effects of diverse exogenous substances at different concentrations on the growth of Polyporus umbellatus mycelium and polysaccharide content and screen out the optimal growth condition for P. umbellatus mycelium， so as to provide a reference for its large-scale artificial cultivation. Method:P. umbellatus mycelium was cultured in media containing different exogenous substances using the method for fungal culturing in plate. The growth rate of the mycelium was judged by the colony diameter and the polysaccharide content was determined by the phenol-sulfuric acid method. Result:The high-dose cyclic adenosine monophosphate， 6-benzyl aminopurine （6-BA）， gibberellic acid （GA）， 2，4-dichlorophenoxyacetic acid （2，4-D）， vitamin （V） B₁， VB₃， VB₆， VB₉， and VB₁₂ all promoted the growth of P. umbellatus mycelium and elevated polysaccharides content. By contrast， indole acetic acid （IAA）， VC， and VB₂ inhibited its growth， with the most obvious inhibition detected in the high-dose VC group. IAA and VB₂ both reduced the polysaccharide content， whereas the high-dose VC significantly increased the polysaccharide content. Cyclic adenosine monophosphate， 6-BA， GA， 2，4-D， VB₁， VB₃， VB₆， VB₉， and VB₁₂ at the concentrations of 2 mmol·L^-1， 6 mg·L^-1， 15 mg·L^-1， 2 mg·L^-1， 4 mg·L^-1， 2 mg·L^-1， 4 mg·L^-1， 6 mg·L^-1， and 10 mg·L^-1， respectively， contributed to the growth of P. umbellatus mycelium and polysaccharide accumulation. Conclusion:The growth of P. umbellatus mycelium and polysaccharide accumulation can be regulated by adding exogenous substances to the culture medium.

ObjectiveTo examine the changes in the immune functions of CD8⁺ T cells in the spleen of mice following Echinococcus multilocularis infections at various doses and at different time points. MethodsThe E. multilocularis protoscoleces were collected, and E. multilocularis infection was modeled in mice via the hepatic portal vein at doses of 50 (low-dose), 500 (medium-dose) and 2 000 protoscoleces (high-dose), while physiological saline served as controls. Mouse spleen was isolated 2 (earlystage), 12 (middle-stage) and 24 weeks post-infection (late-stage), and spleen lymphocytes were harvested. The phenotype of memory CD8⁺ T cells and 2B4 expression were quantified in the mouse spleen, and the secretion of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-17A and IL-10 was measured. Results A central-memory phenotype was predominant in the CD8⁺ T cells in the spleen of mice at the early stage of high-dose protoscolece infections, and the proportion of central-memory CD8⁺ T cells was significantly greater in the high-dose group than in the control group (35.50% ± 2.00% vs. 25.90% ± 2.46%, P < 0.01), while a effector- memory phenotype was predominant in the CD8⁺ T cells in the spleen of mice at the late stage of medium- and high-dose protoscolece infections, and the proportions of effector-memory CD8⁺ T cells were significantly greater in the medium- (25.70% ± 4.12%) and high-dose group (28.40% ± 4.12%) than in the control group (10.50% ± 6.45%) (P < 0.05). The proportions of the central-memory CD8⁺ T cells were significantly higher in the high-dose group than at middle and late stages than at the early stage (P < 0.01), and the proportion of effector-memory CD8⁺ T cells was significantly greater in the high-dose group at the late stage than at early and middle stages (P < 0.05). The secretion of IFN-γ and IL-17A by spleen CD8⁺ T cells was elevated in the low- and medium-dose groups at the early stage of infection, and high-dose protoscolece infection promoted the secretion of IFN-γ and TNF-α by spleen CD8⁺ T cells; however, the levels of IFN-γ and TNF-α were significantly lower at the late stage than at the early and middle stages (P < 0.05). In addition, high 2B4 expression was detected in spleen CD8⁺ T cells in the middle- and high-dose groups at the late stage of infection, and the 2B4 expression was significantly higher in the medium(4.73% ± 1.56%) and high-dose groups (4.94% ± 1.90%) than in the low-dose group (2.49% ± 0.58%) and the control group (2.92% ± 0.60%) (P < 0.05). Conclusions E. multilocularis may be killed and eliminated through the host immune responses at the middle and late stages of low- and medium-dose protoscolece infections, while high-dose protoscolece infections may trigger the upregulation of 2B4 expression in mouse spleen CD8⁺ T cells at the late stage, which leads to immune exhaustion and the resultant chronic infections.

Objective To analyze the clinical courses and outcomes of COVID-19 cases and the influencing factors in Guangdong province and provide basis for the formulation or adjustment of medical care and epidemic control strategy for COVID-19. Methods We collected demographic data, medical histories, clinical courses and outcomes of 1 350 COVID-19 patients reported in Guangdong as of 4 March 2020 via epidemiological investigation and process tracking. Disease severity and clinical course characteristics of the patients and influencing factors of severe illness were analyzed in our study. Results Among 1 350 cases of COVID-19 cases in Guangdong, 72 (5.3%) and 1049 (77.7%) were mild and ordinary cases, 164 (12.1%) were severe cases, 58 (4.3%) were critical cases and 7 (0.5%) were fatal. The median duration of illness were 23 days ( P 25 - P 75 : 18-31 days) and the median length of hospitalization were 20 days ( P 25 - P 75 : 15-27 days). For severe cases, the median time of showing severe manifestations was on the 12th day after onset ( P 25 - P 75 : 9th to 15th days), and the median time of severe manifestation lasted for 8 days P 25 - P 75 : 4-14 days). Among 1 066 discharged/fetal cases, 36.4% (36/99) and 1.0% (1/99) of the mild cases developed to ordinary cases and severe cases respectively after admission; and 5.2% (50/968) and 0.6% (6/968) of the ordinary cases developed to severe cases, and critical cases respectively after admission. In severe cases, 11.4% developed to critical cases (10/88). The influencing factors for severe illness or worse included male (a HR =1.87, 95% CI : 1.43-2.46), older age (a HR =1.67, 95% CI : 1.51-1.85), seeking medical care on day 2-3 after onset (a HR =1.73, 95% CI : 1.20-2.50) pre-existing diabetes (a HR =1.75, 95% CI : 1.12-2.73) and hypertension (a HR =1.49, 95% CI : 1.06-2.09). Conclusions The course of illness and length of hospitalization of COVID-19 cases were generally long and associated with severity of disease clinical outcomes. The severe cases were mainly occurred in populations at high risk. In the epidemic period, classified management of COVID-19 cases should be promoted according to needs for control and prevention of isolation and treatment for the purpose of rational allocation of medical resources.