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 an artificial intelligence (AI)-based platelet review strategy to identify abnormal platelet histograms with no significant difference between initial impedance platelet count (PLT-I) and PLT-F results.Methods:This study included 5 119 routine blood analysis in Nanfang Hospital of Southern Medical University and its Ganzhou branch from July 2023 and March 2024. Specimens exhibiting abnormal platelet histograms and an initial platelet count >40×10?/L underwent review using the fluorescent platelet count (PLT-F) channel. Consistency of the results was defined as a difference between impedance platelet count (PLT-I) and PLT-F less than ±20% of the PLT-F results. A deep learning model was developed using platelet and red blood cell histogram data from a training set of 3 807 specimens. The model′s diagnostic performance was evaluated on an independent external validation set ( n=805) using receiver operating characteristic (ROC) curve analysis. Changes in the number of reviewed samples and sample turnaround time were analyzed to assess its clinical utility. Results:The deep learning model based on platelet and red blood cell histograms achieved an area under the ROC curve (AUC) of 0.854 in the training set. At a cutoff value of 0.1, the sensitivity was 0.954 and specificity was 0.358. The model could reduce review by 16.80% (190/1 131). In the validation set, the AUC was 0.805, with a sensitivity of 0.955 and specificity of 0.307, corresponding to a reduction of 17.41% (47/270) in reviewed specimens.Conclusion:The platelet review prediction model developed based on deep learning technology can efficiently identify samples with consistent results before and after review, reducing unnecessary reviews and shortening specimen testing time, thereby improving the efficiency of platelet test.

Objective:To investigate the correlation between serum calcium binding protein S100A9 levels and lung function in patients with idiopathic pulmonary fibrosis (IPF).Method:A retrospective case-control study was conducted. Forty patients diagnosed with IPF in respiratory department from January 4, 2023, to January 30, 2024 were selected as the IPF group,with a mean age of (65.3±8.4) years old, including 29 males and 11 females. while 50 healthy volunteers receiving health examinations in our physical examination center were enrolled in this study, including 38 males and 12 females, with a mean age of (64.1±6.3) years. The levels of biochemical parameters were assayed with biochemical analyzer. S100A9 levels were determined by Enzyme linked immunosorbent assay. The lung function test results of all participants were recorded. SPSS 19.0 statistical software was used to compare the differences of biomarkers levels between the two groups , Using parameter testing (independent sample t-test) to compare the differences in serum S100A9 levels and lung function between the two groups, the enumeration data were treated with the chi-square test. Pearson correlation analysis was used to evaluate the correlation between S100A9 and lung function, the influencing factors of IPF were analyzed by using multivariate logistic regression model, and receiver operating characteristic (ROC) curve analysis was used to assess the value of Calprotectin S100A9 in predicting IPF. Results:The serum S100A9 levels in the IPF group were significantly higher than those in the healthy control group [(132.47±21.46) pg/ml,(44.75±8.84) pg/ml, t=3.544, P<0.05], forced expiratory volume in one second(FEV1,1.38±0.19) L, forced vital capacity (FVC, 2.38±0.59) L, FEV1/FVC (57.98±6.13), the maximum spontaneous ventilation (MVV, 57.48±7.66) L/min was lower than that of the control group [(3.24±0.65) L, (3.65±0.67) L, (88.77±7.97), (86.34±7.23) L/min, t=3.486,3.393,2.771,3.462, P<0.05]. Serum S100A9 was negatively correlated with FEV1, FVC, FEV1/FVC, and MVV ( r=-0.537,-0.458,-0.489,-0.511, P<0.05), S100A9 was positively correlated with S100A9 in bronchoalveolar lavage fluid and high-resolution CT fibrosis score ( r=0.632, r=0.517, P<0.05).The area under the curve (AUC) of S100A9 for predicting IPF was 0.691. Conclusion:The level of calcium binding protein S100A9 was significantly increased in IPF patients, and was closely related to decreased lung ventilation function and the occurrence of IPF, which might serve as a marker for evaluating pulmonary fibrosis.

Objective:To investigate the correlation between serum calcium binding protein S100A9 levels and lung function in patients with idiopathic pulmonary fibrosis (IPF).Method:A retrospective case-control study was conducted. Forty patients diagnosed with IPF in respiratory department from January 4, 2023, to January 30, 2024 were selected as the IPF group,with a mean age of (65.3±8.4) years old, including 29 males and 11 females. while 50 healthy volunteers receiving health examinations in our physical examination center were enrolled in this study, including 38 males and 12 females, with a mean age of (64.1±6.3) years. The levels of biochemical parameters were assayed with biochemical analyzer. S100A9 levels were determined by Enzyme linked immunosorbent assay. The lung function test results of all participants were recorded. SPSS 19.0 statistical software was used to compare the differences of biomarkers levels between the two groups , Using parameter testing (independent sample t-test) to compare the differences in serum S100A9 levels and lung function between the two groups, the enumeration data were treated with the chi-square test. Pearson correlation analysis was used to evaluate the correlation between S100A9 and lung function, the influencing factors of IPF were analyzed by using multivariate logistic regression model, and receiver operating characteristic (ROC) curve analysis was used to assess the value of Calprotectin S100A9 in predicting IPF. Results:The serum S100A9 levels in the IPF group were significantly higher than those in the healthy control group [(132.47±21.46) pg/ml,(44.75±8.84) pg/ml, t=3.544, P<0.05], forced expiratory volume in one second(FEV1,1.38±0.19) L, forced vital capacity (FVC, 2.38±0.59) L, FEV1/FVC (57.98±6.13), the maximum spontaneous ventilation (MVV, 57.48±7.66) L/min was lower than that of the control group [(3.24±0.65) L, (3.65±0.67) L, (88.77±7.97), (86.34±7.23) L/min, t=3.486,3.393,2.771,3.462, P<0.05]. Serum S100A9 was negatively correlated with FEV1, FVC, FEV1/FVC, and MVV ( r=-0.537,-0.458,-0.489,-0.511, P<0.05), S100A9 was positively correlated with S100A9 in bronchoalveolar lavage fluid and high-resolution CT fibrosis score ( r=0.632, r=0.517, P<0.05).The area under the curve (AUC) of S100A9 for predicting IPF was 0.691. Conclusion:The level of calcium binding protein S100A9 was significantly increased in IPF patients, and was closely related to decreased lung ventilation function and the occurrence of IPF, which might serve as a marker for evaluating pulmonary fibrosis.

Objective:To develop an artificial intelligence (AI)-based platelet review strategy to identify abnormal platelet histograms with no significant difference between initial impedance platelet count (PLT-I) and PLT-F results.Methods:This study included 5 119 routine blood analysis in Nanfang Hospital of Southern Medical University and its Ganzhou branch from July 2023 and March 2024. Specimens exhibiting abnormal platelet histograms and an initial platelet count >40×10?/L underwent review using the fluorescent platelet count (PLT-F) channel. Consistency of the results was defined as a difference between impedance platelet count (PLT-I) and PLT-F less than ±20% of the PLT-F results. A deep learning model was developed using platelet and red blood cell histogram data from a training set of 3 807 specimens. The model′s diagnostic performance was evaluated on an independent external validation set ( n=805) using receiver operating characteristic (ROC) curve analysis. Changes in the number of reviewed samples and sample turnaround time were analyzed to assess its clinical utility. Results:The deep learning model based on platelet and red blood cell histograms achieved an area under the ROC curve (AUC) of 0.854 in the training set. At a cutoff value of 0.1, the sensitivity was 0.954 and specificity was 0.358. The model could reduce review by 16.80% (190/1 131). In the validation set, the AUC was 0.805, with a sensitivity of 0.955 and specificity of 0.307, corresponding to a reduction of 17.41% (47/270) in reviewed specimens.Conclusion:The platelet review prediction model developed based on deep learning technology can efficiently identify samples with consistent results before and after review, reducing unnecessary reviews and shortening specimen testing time, thereby improving the efficiency of platelet test.

DPP4 is a serine exopeptidase that is immobilized on the cell membrane and plays a crucial regulatory role in various physiological and pathological activities within the human body.In addition to acting as a transcription factor to regulate the tran-scription and expression of downstream target genes,DPP4 also functions as a transcription-independent regulator through pro-tein-protein interactions.In recent studies,DPP4 has been strongly linked to various diseases,and several substances with the potential to target DPP4 have been identified.This paper mainly reviews the multifunctionality of DPP4 in regulating vari-ous aspects of energy metabolism,inflammation,tissue repair and carcinogenesis in the body.It also reviews the screening of in vitro inhibitors of DPP4 and its research progress in regulating chronic liver disease,based on the pathological development process of chronic liver disease.

Objective To observe the effect of Renshen(ginseng)-Yuzhu(fragrant solomonseal rhizome)on inflammatory factors and inflammasomes in depression rats,and to explore the antidepressant mechanism of Renshen-Yuzhu.Methods Fifty male SD rats were divided into the blank group,model group,fluoxetine group(2.1 mg/kg),Renshen-Yuzhu low-dose group(1.89 g/kg),and Renshen-Yuzhu high-dose group(5.67 g/kg),with ten rats in each group.Except for the blank group,the rats in the other groups were treated with chronic unpredictable mild stress to establish a depression rat model.On the second day after the end of modeling,the rats in each group were given the corresponding drugs once daily for 14 days.After modeling and dosing,body weight,forced swimming immobility time,and sucrose preference rate were measured.After dosing,hematoxylin-eosin staining was used to detect neuronal damage in the cerebral cortex,enzyme-linked immunosorbent assay was used to detect the contents of interleukin-4(IL-4),interleukin-23(IL-23),and interleukin-27(IL-27)in cortex,real-time PCR was used to detect the mRNA expression of interleukin-24(IL-24)in cortex,and the protein expressions of nucleotide-binding oligomerization domain-like receptor protein 1(NLRP1),absent in melanoma 2(AIM2),and nucleotide-binding oligomerization domain-like receptor protein 4(NLRC4)were detected by Western blotting.Results After dosing,compared with the blank group,the body weight of the model group decreased,the sucrose preference rate decreased,the swimming immobility time was prolonged,the neuronal tissue in cortex was destroyed,the content of IL-4 in cortex decreased,the contents of IL-23 and IL-27 in cortex increased,and the protein expressions of NLRP1,AIM2 and NLRC4 in cortex increased(P＜0.01).Compared with the model group,the body weight of rats in each administration group increased,the sucrose preference rate increased,the swimming immobility time was shortened,the damage of neuronal tissues in cortex improved,the content of IL-4 in cortex increased,the contents of IL-23 and IL-27 in cortex decreased,and the protein expressions of NLRP 1,AIM2 and NLRC4 in cortex decreased(P＜0.05).Conclusion Renshen-Yuzhu couplet medicines can improve the depressive-like behavior and exert antidepressant effect in chronic stress rats,and its mechanism may be related to the inhibition of NLRP 1,NLRC4,AIM2 inflammasome activation and its mediated inflammatory response in cortex,reducing pro-inflammatory cytokines,and increasing the level of antiinflammatory cytokines.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

In this study, we investigated the effects of Panax notoginseng saponins (PNS) on pulmonary vascular remodeling and ADAM10/Notch3 pathway in pulmonary arterial hypertension (PAH). PAH rat model was established, and male Sprague Dawley (SD) rats were randomly divided into control group, monocrotaline (MCT) group and MCT+PNS group, with 10 rats in each group. Rats in the control group were intraperitoneally injected with equal volume of normal saline. Rats in the MCT group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with the same volume of normal saline every day. Rats in the MCT+PNS group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with 50 mg/kg PNS every day. The modeling time of each group lasted for 21 days. After the model was established, the mean pulmonary artery pressure (mPAP) was measured by right heart catheterization technique, the right ventricular hypertrophy index (RVHI) was calculated, the microscopic morphology and changes of pulmonary vascular wall were observed by HE and Masson staining, and the expressions of ADAM10, Notch3, Hes-1, P27, PCNA, Caspase-3 proteins and mRNA in pulmonary vascular tissue of rats were detected by Western blot and qPCR. The expression and localization of Notch3 and α-SMA were detected by immunofluorescence staining. The protein expression of ADAM10 was detected by immunohistochemical staining. The results showed that compared with the control group, mPAP, RVHI, pulmonary vessels and collagen fibers in the MCT group were significantly increased, the expressions of ADAM10, Notch3, Hes-1, and PCNA protein and mRNA were significantly increased, while the expressions of P27 and Caspase-3 protein and mRNA were decreased significantly. Compared with the MCT group, mPAP and RVHI were significantly decreased, pulmonary vessels were significantly improved and collagen fibers were significantly reduced, the expressions of protein and mRNA of ADAM10, Notch3, Hes-1, and PCNA were decreased in MCT+PNS group, but the expressions of protein and mRNA of P27 and Caspase-3 were increased slightly. The results of immunofluorescence showed that Notch3 and α-SMA staining could overlap, which proved that Notch3 was expressed in smooth muscle cells. The expression of Notch3 in the MCT group was increased significantly compared with that in the control group, while PNS intervention decreased the expression of Notch3. Immunohistochemical staining showed that compared with the control group, the amount of ADAM10 in the MCT group was increased significantly, and the expression of ADAM10 in the MCT+PNS group was decreased compared with the MCT group. These results indicate that PNS can improve the PAH induced by MCT in rats by inhibiting ADAM10/Notch3 signaling pathway.
Animals ; Male ; Rats ; Caspase 3/metabolism* ; Collagen ; Disease Models, Animal ; Hypertension, Pulmonary/drug therapy* ; Monocrotaline/adverse effects* ; Panax notoginseng/chemistry* ; Proliferating Cell Nuclear Antigen/pharmacology* ; Pulmonary Arterial Hypertension ; Pulmonary Artery/metabolism* ; Rats, Sprague-Dawley ; Receptor, Notch3/genetics* ; RNA, Messenger ; Saline Solution ; Signal Transduction ; Saponins/pharmacology*

Objective:To investigate the feasibility and safety of a novel single-port robotic surgical system with flexible 3D endoscope and deformable surgical instruments in zero ischemic partial nephrectomy.Methods:From May 2021 to October 2021, a prospective study on patients with renal tumor who plan to receive zero ischemic partial nephrectomy was conducted. Inclusion criteria included over 18 years old, body index between 18.5 to 30.0 kg/m2, American Society of Anesthesiologists Score ranged from 1 to 3 points, cooperation with the follow-up and related examinations, voluntary in participating the clinical trial and signing the informed consent. Exclusion criteria included patients with other co-existed malignant tumors or a medical history of other malignant tumors, the patients who have received the same urological surgery in the past, the patients who underwent or plan to undergo other major operations 3 months before or after the surgery, the patients with active pulmonary tuberculosis or severe systemic diseases, the patients to be considered not suitable to enroll in by the researchers. A novel single-port robotic surgical system was used to perform the surgery. The system consiststed of a remote control console, a surgical equipment cart, a four-arm operation cart and deformable robotic instruments which were reusable. The two-section deformable robotic instruments were able to bend in four directions and carried different surgical instruments such as unipolar scissors, bipolar grasping forceps and needle holders. The deformable robotic instruments entered the body through a special trocar with single hole and multi-channel, and then unfolded in a triangle. By bending instruments, surgeons could perform single-port robotic surgery without the trouble of "chopstick effect" or "reverse direction" . Four cases of single-port partial nephrectomy were carried out. Under general anesthesia, the patients were taken the lateral recumbent position, with elevated waist and lowered head and feet. A 3-4 cm incision was taken layer by layer along the lateral edge of the rectus abdominis at the umbilicus level. A special 2.5 cm robotic trocar was set into the cavity, and a high-definition 3D laparoscopic lens and a snake shaped mechanical arm were then put into the abdominal cavity through the trocar. All operations were performed by transperitoneal approach with an auxiliary port through the same or a different skin incision if necessary. Tumor resection and renal reconstruction were performed by the way of zero ischemia. The perioperative parameters such as tumor size, operation time, intraoperative bleeding and postoperative complications were analyzed.Results:Four patients were involved, including 2 males and 2 females, with 2 of them having a history of hypertension. The ECOG scores were all 0, and KPS score was 100 in 3 cases and 90 in 1 case. Preoperative mean serum creatinine was (76.8±18.8)μmol/L (range 70-104 μmol/L). The tumors were located on the left in 3 cases and on the right in 1 case. The diameter of the tumor ranged from 1.1 to 2.8 cm, with the TNM classification of T 1a. The R. E.N.A.L. scores were 4a, 7p, 6p and 4P respectively. The first operation was performed by pure single-port surgery, and the other 3 cases were performed with the help of an auxiliary port to ensure the safety .The operation time ranged from 155 min to 210 min, and the intraoperative bleeding ranged from 20 ml to 170 ml. Postoperative pathology showed 2 cases of renal clear cell carcinoma with negative margin and 2 cases of angiomyolipoma. No severe complications, such as bleeding or urinary leakage, were observed during the perioperative period, and the change of serum creatinine was insignificant before discharge and before operation( P=0.24). Conclusions:A robotic single-port partial nephrectomy can be successfully carried out by using this novel single-port robotic surgical system with flexible 3D endoscope and deformable surgical instruments.