Objective: To investigate the factors influencing intraoperative blood transfusion in patients with hip fractures and to develop a machine learning (ML) model for predicting this risk. Methods: A total of 424 patients with hip fractures who underwent surgical treatment between November 2022 and March 2025 in our hospital were selected. Key feature variables of intraoperative blood transfusion risk were identified using the Boruta algorithm. Four different ML algorithms—support vector machine (SVM), linear discriminant analysis (LDA), mixed discriminant analysis (MDA), and extreme gradient boosting (XGBoost)—were used to develop predictive models for intraoperative blood transfusion risk. The predictive performance of the four ML models were evaluated using accuracy, precision, receiver operating characteristic (ROC) curves, precision-recall curves (PRC), precision-recall gain curves (PRGC), and F1 scores. Shapley additive interpretation (SHAP) was used to interpret the final model. Results: Among the 424 patients, 77(18.2%) received intraoperative blood transfusion. The Boruta algorithm identified albumin (ALB), activated partial thromboplastin time (APTT), types of anesthesia, types of fracture, and hemoglobin (Hb) as key feature variables for predicting intraoperative blood transfusion risk. In model evaluation, the SVM model outperforms the other three models across multiple metrics, including the area under the receiver operating characteristic curve (AUC), recall, recall gain, accuracy, precision, F1 score, and the area under the precision-recall curve (PRC-AUC). The SVM model, interpreted and visualized based on SHAP values, effectively predicted intraoperative blood transfusion risk in patients with hip fracture. A visual online application was developed based on the SVM model (https://pbo-nomogram.shinyapps.io/blood/). Conclusion: Preoperative low ALB and Hb levels, prolonged APTT, general anesthesia, and intertrochanteric fractures are risk factors for intraoperative blood transfusion in hip fracture patients. The risk prediction model for intraoperative blood transfusion constructed based on the SVM algorithm has optimal performance, which provides new ideas and methods for the clinical early identification of hip fracture patients with high transfusion risk and the implementation of targeted interventions.

Breast cancer prevention and treatment have become major issues that urgently need to be addressed in the field of global public health. As a key pathological transitional stage in the progression of breast cancer， preneoplastic breast cancer （PBC） carries a significant risk of clinical transformation. Effective intervention in the progression of PBC is of great clinical significance in preventing the occurrence of breast cancer. Pathological studies have shown that abnormal angiogenesis is a key mechanism driving the transformation of PBC into breast cancer. Vascular endothelial growth factor （VEGF）， as a core regulatory molecule that promotes angiogenesis， plays a pivotal role in this process. The malignant transformation of PBC is closely associated with the abnormal activation of the VEGF-mediated pro-angiogenic network. Although modern medicine has achieved certain therapeutic effects through surgery and endocrine therapy， clinical limitations such as invasiveness， drug resistance， and adverse reactions still exist. Recent studies have demonstrated that the VEGF signaling system mediates the phosphatidylinositol 3-kinase-protein kinase B （PI3K/Akt） signaling pathway and the mitogen-activated protein kinase （MAPK） pathway. In addition， the hypoxia-inducible factor-1α （HIF-1α）/VEGF signaling pathway and the delta-like ligand 4 （DLL4）/Notch receptor 1 （Notch1） signaling pathway， together with other pathways， form a complex regulatory network that plays a central role in angiogenesis during PBC. Traditional Chinese medicine （TCM）， characterized by multi-component synergy， multi-pathway regulation， and high safety， demonstrates significant advantages in inhibiting pathological angiogenesis and blocking PBC progression by targeting the VEGF signaling pathway. From the perspective of VEGF pathway regulation， this paper systematically reviews the latest research progress on TCM in inhibiting angiogenesis and intervening in PBC， and discusses its mechanisms and application value in the early prevention and treatment of PBC， with the aim of providing references for optimizing clinical intervention strategies for PBC.

Objective To investigate correlations of the ratio of specific brain region volume to total brain volume(ratio％),standard uptake value(SUV)of specific brain region based on 18F-FDG PET/MR examination in Alzheimer disease(AD)patients,as well as the relationship between changes of these two.Methods Fifty AD patients were retrospectively collected.Based on FDG PET/MR,the ratio％and the mean SUV(SUVmean)of 40 specific brain regions were obtained,and the correlation between ratio％and SUVmean for each region were evaluated.According to a database of normal brains,Z-scores for ratio％and SUVmean were calculated to represent structural and functional changes in AD patients,and the correlation between these 2 Z-scores was assessed.Results Correlations were found between ratio％and SUVmean,also between Z-scores of these two parameters in 29 brain regions(r=0.288 to 0.778,all P＜0.05).Among them 7 brain regions,i.e.bilateral middle temporal gyrus,right fusiform gyrus,right hippocampus,right precuneus,left lingual gyrus and right parahippocampal gyrus exhibited correlation coefficients greater than 0.6.Conclusion There were some relationships between brain structural and metabolic functions and their changes in AD patients showed on FDG PET/MR.

Objective:To explore the specific mechanism of lactic acid(LA)on regulating decidual macrophage differentia-tion in pre-eclampsia(PE)through non-receptor tyrosine kinase sarcoma virus protein/lactate dehydrogenase A(SRC/LDHA)signaling pathway.Methods:Decidual tissues were collected from 16 women with preeclampsia(PE)and 16 women with normal pregnancies during the same period.Immunofluorescence was used to assess macrophage subtypes and LA secretion in decidual tissues.Biochemi-cal assays and Western blot were performed to measure levels of LA,LDHA and MCT-4 in tissues.Biochemical assays were conducted to measure LA level in supernatants of normal trophoblast cells under different cell densities and oxygen conditions.Flow cytometry was used to assess polarization of macrophages in normal decidual tissues under different conditions of LA,oxygen and culture media.qRT-PCR,Western blot,ROS,and NAD+/NADH measurements were performed to evaluate mRNA and protein levels related to gly-colysis and mitochondrial oxidative phosphorylation,as well as proteins associated with SRC/LDHA signaling pathway,ROS level,and NAD+/NADH.Thirty pregnant rats were divided into normal group,model group,low-,medium-,high-dose AZD3965 groups,with 6 rats in each group.PE model was established,and the systolic blood pressure and urinary protein levels of pregnant rats were measured at various time points.On gestational day 20,the placental and fetal development in each group were compared.Immunofluo-rescence was used to assess trophoblast cell invasion and uterine spiral artery remodeling in decidual tissues.Immunohistochemistry and flow cytometry were performed to evaluate fetal vascular development and macrophage polarization.Results:Compared with nor-mal pregnant women,patients with PE exhibited an increased proportion of M1 macrophages,CK7+LDHA+,CK7+MCT-4+cells,LA,LDHA and MCT-4(P<0.05),while proportion of M2 macrophages was decreased(P<0.05).Compared with normoxic conditions,LA level in supernatant of trophoblast cells was significantly increased under hypoxic conditions(P<0.05).Under normoxic condition,compared with control groups,conditioned culture group showed a decreased M1/M2 macrophage(P<0.05).LA group exhibited in-creased expressions of NDUFA1,NDUFA2,UQCRC1,UQCRC2,COX4I1,COX4I2,ATP5F1A,ATP5F1B mRNA,and SDHB,COX4I1,LDHB,p-SRC(Y416),p-LDHA(Y10),VEGF and ARG-1 protein(P<0.05).NAD+/NADH was decreased(P<0.05).PX478 group showed increased expression of p-SRC(P<0.05).LA+PX478 group exhibited increased expressions of p-SRC(Y416)and p-LDHA(Y10)(P<0.05),while VEGF expression was decreased(P<0.05).Under hypoxic conditions,compared with control groups,the conditioned culture group,LA group and LA+PX478 group exhibited an increased M1/M2 macrophage(P<0.05).LA group showed upregulated expressions of LDHA mRNA,HIF-1α,LDHA,p-SRC(Y416),p-LDHA(Y10)and iNOS(P<0.05),while mRNA expression of LDHB and protein expressions of NDUFA1 and UQCRC2 were downregulated(P<0.05).ROS level and NAD+/NADH were decreased(P<0.05).PX478 group demonstrated reduced HIF-1α expression(P<0.05)and increased p-SRC(Y416)expression(P<0.05).LA+PX478 group showed decreased HIF-1α expression(P<0.05)and increased p-LDHA(Y10)ex-pression(P<0.05).Compared with LA group,LA+PX478 group exhibited elevated ROS level(P<0.05)and a reduced NAD+/NADH(P<0.05).Compared with normal group,pregnant rats in model group exhibited increased blood pressure,urine protein levels and an elevated M1/M2 in decidual tissue(P<0.05).The fetal mice exhibited abnormal development,with inadequate trophoblast cell infiltra-tion,impaired uterine spiral artery remodeling,a decreased number of fetal blood vessels in placental labyrinthine layer,and nar-rowed lumens.Compared with model group,the low,medium,and high-dose AZD3965 groups showed decreased blood pressure,urine protein levels and M1/M2(P<0.05).Additionally,there was an improvement in fetal mouse development,trophoblast cell infil-tration and uterine spiral artery remodeling.The number of fetal blood vessels in placental labyrinthine layer increased,and the lu-mens expanded.Conclusion:LA can regulate macrophage polarization in decidua of PE through SRC/LDHA pathway,and blocking LA uptake can alleviate the pathological manifestations in pregnant rats with PE.

Objective:To explore the specific mechanism of lactic acid(LA)on regulating decidual macrophage differentia-tion in pre-eclampsia(PE)through non-receptor tyrosine kinase sarcoma virus protein/lactate dehydrogenase A(SRC/LDHA)signaling pathway.Methods:Decidual tissues were collected from 16 women with preeclampsia(PE)and 16 women with normal pregnancies during the same period.Immunofluorescence was used to assess macrophage subtypes and LA secretion in decidual tissues.Biochemi-cal assays and Western blot were performed to measure levels of LA,LDHA and MCT-4 in tissues.Biochemical assays were conducted to measure LA level in supernatants of normal trophoblast cells under different cell densities and oxygen conditions.Flow cytometry was used to assess polarization of macrophages in normal decidual tissues under different conditions of LA,oxygen and culture media.qRT-PCR,Western blot,ROS,and NAD+/NADH measurements were performed to evaluate mRNA and protein levels related to gly-colysis and mitochondrial oxidative phosphorylation,as well as proteins associated with SRC/LDHA signaling pathway,ROS level,and NAD+/NADH.Thirty pregnant rats were divided into normal group,model group,low-,medium-,high-dose AZD3965 groups,with 6 rats in each group.PE model was established,and the systolic blood pressure and urinary protein levels of pregnant rats were measured at various time points.On gestational day 20,the placental and fetal development in each group were compared.Immunofluo-rescence was used to assess trophoblast cell invasion and uterine spiral artery remodeling in decidual tissues.Immunohistochemistry and flow cytometry were performed to evaluate fetal vascular development and macrophage polarization.Results:Compared with nor-mal pregnant women,patients with PE exhibited an increased proportion of M1 macrophages,CK7+LDHA+,CK7+MCT-4+cells,LA,LDHA and MCT-4(P<0.05),while proportion of M2 macrophages was decreased(P<0.05).Compared with normoxic conditions,LA level in supernatant of trophoblast cells was significantly increased under hypoxic conditions(P<0.05).Under normoxic condition,compared with control groups,conditioned culture group showed a decreased M1/M2 macrophage(P<0.05).LA group exhibited in-creased expressions of NDUFA1,NDUFA2,UQCRC1,UQCRC2,COX4I1,COX4I2,ATP5F1A,ATP5F1B mRNA,and SDHB,COX4I1,LDHB,p-SRC(Y416),p-LDHA(Y10),VEGF and ARG-1 protein(P<0.05).NAD+/NADH was decreased(P<0.05).PX478 group showed increased expression of p-SRC(P<0.05).LA+PX478 group exhibited increased expressions of p-SRC(Y416)and p-LDHA(Y10)(P<0.05),while VEGF expression was decreased(P<0.05).Under hypoxic conditions,compared with control groups,the conditioned culture group,LA group and LA+PX478 group exhibited an increased M1/M2 macrophage(P<0.05).LA group showed upregulated expressions of LDHA mRNA,HIF-1α,LDHA,p-SRC(Y416),p-LDHA(Y10)and iNOS(P<0.05),while mRNA expression of LDHB and protein expressions of NDUFA1 and UQCRC2 were downregulated(P<0.05).ROS level and NAD+/NADH were decreased(P<0.05).PX478 group demonstrated reduced HIF-1α expression(P<0.05)and increased p-SRC(Y416)expression(P<0.05).LA+PX478 group showed decreased HIF-1α expression(P<0.05)and increased p-LDHA(Y10)ex-pression(P<0.05).Compared with LA group,LA+PX478 group exhibited elevated ROS level(P<0.05)and a reduced NAD+/NADH(P<0.05).Compared with normal group,pregnant rats in model group exhibited increased blood pressure,urine protein levels and an elevated M1/M2 in decidual tissue(P<0.05).The fetal mice exhibited abnormal development,with inadequate trophoblast cell infiltra-tion,impaired uterine spiral artery remodeling,a decreased number of fetal blood vessels in placental labyrinthine layer,and nar-rowed lumens.Compared with model group,the low,medium,and high-dose AZD3965 groups showed decreased blood pressure,urine protein levels and M1/M2(P<0.05).Additionally,there was an improvement in fetal mouse development,trophoblast cell infil-tration and uterine spiral artery remodeling.The number of fetal blood vessels in placental labyrinthine layer increased,and the lu-mens expanded.Conclusion:LA can regulate macrophage polarization in decidua of PE through SRC/LDHA pathway,and blocking LA uptake can alleviate the pathological manifestations in pregnant rats with PE.

Objective To elucidate the molecular mechanisms underlying the effects of Kanggan Mixture(KGM)on key targets in rats with acute lung injury,network pharmacology and in vivo micro-CT experiments were employed.Methods Network pharmacology was utilized to forecast the target genes and principal pathways involved in the intervention of KGM in acute lung injury(ALI).Lipopolysaccharide(LPS)-induced ALI rat models were utilized,and micro-computed tomography(micro-CT)was employed to evaluate the extent of lung injury in vivo.Experiments were conducted to verify the intervention mechanism of KGM on ALI rats.Results The findings revealed that 190 chemical constituents were identified from KGM,and 579 potential targets and 204 pathways associated with KGM's impact on ALI were predicted.The principal components of KGM,such as quercetin,luteolin,kaempferol,betulin,and lupenone,exhibit anti-viral,anti-inflammatory,and immunomodulatory properties by targeting TP53,AKT1,SRC,EP300,and STAT3,and modulating the FoxO signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,and MAPK signaling pathway,demonstrating an influence on acute lung injury.Micro-CT results suggest that KGM can improve lung texture enhancement and lung injury in ALI rats,with an increase in end-expiratory lung volume(inspiratory phase-expiratory phase).The HE and W/D ratio results indicate that KGM can improve lung tissue injury and reduce the lung tissue wet/dry weight ratio(P<0.01).Blood cell analysis results show that the anti-inflammatory agent can decrease the WBC(white blood cell count)and N%(neutrophil percentage)in ALI rats'blood(P<0.01),and increase lymphocytes(P<0.05).Real-time quantitative PCR,WES,and immunohistochemistry results suggest that KGM can decrease the mRNA expression,protein distribution,and protein expression levels of TP53,AKT1,SRC,EP300,and STAT3 in lung tissue of ALI rats(P<0.05).Conclusion KGM has a certain intervention effect on acute lung injury,mainly achieved through the core targets STAT3,EP300,SRC,AKT1,and TP53.

Objective To investigate correlations of the ratio of specific brain region volume to total brain volume(ratio％),standard uptake value(SUV)of specific brain region based on 18F-FDG PET/MR examination in Alzheimer disease(AD)patients,as well as the relationship between changes of these two.Methods Fifty AD patients were retrospectively collected.Based on FDG PET/MR,the ratio％and the mean SUV(SUVmean)of 40 specific brain regions were obtained,and the correlation between ratio％and SUVmean for each region were evaluated.According to a database of normal brains,Z-scores for ratio％and SUVmean were calculated to represent structural and functional changes in AD patients,and the correlation between these 2 Z-scores was assessed.Results Correlations were found between ratio％and SUVmean,also between Z-scores of these two parameters in 29 brain regions(r=0.288 to 0.778,all P＜0.05).Among them 7 brain regions,i.e.bilateral middle temporal gyrus,right fusiform gyrus,right hippocampus,right precuneus,left lingual gyrus and right parahippocampal gyrus exhibited correlation coefficients greater than 0.6.Conclusion There were some relationships between brain structural and metabolic functions and their changes in AD patients showed on FDG PET/MR.

Objective:To evaluate the cumulative live birth rate (CLBR) and cost-effectiveness of fixed versus adjusted follicle-stimulation hormone (FSH) dosages in infertile women with different ovarian responses during their first assisted reproductive technology (ART) cycle.Methods:A retrospective real-world cohort study was conducted on 5 419 infertile women who underwent their first ART treatment at the Department of Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2017. All patients received an individualized starting dosage of gonadotropin. Based on whether FSH dosages were adjusted during controlled ovarian stimulation (COS), patients were divided into fixed-dosage group ( n=2 061) and adjusted-dosage group ( n=3 358). Clinical outcomes and FSH cost-effectiveness were compared between the two groups across different ovarian response groups, with CLBR as the primary outcome. Propensity score matching (PSM) and multivariable logistic regression were used to adjust for potential confounders. Results:FSH dosage adjustments were found in 62.0% (3 358/5 419) of cycles during COS. After PSM, baseline characteristics were comparable between the two groups (all P>0.05). After adjusting for confounders using multivariable logistic regression, FSH dosage adjustment was not significantly associated with CLBR ( OR=1.06, 95% CI: 0.94-1.20, P=0.332). Compared with the adjusted-dosage group, the fixed-dosage group showed no significant differences in CLBR in poor-, normal-, and high-responder groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) did not differ significantly between the two groups ( P>0.05). In poor-, normal-, and high-responder groups, the total FSH dosages in the fixed-dose group [1 350 (375, 1 825) U, 1 200 (375, 1 500) U and 525 (375, 1 128) U, respectively] were significantly lower than those in the adjusted-dose group [1 875 (1 425, 2 294) U, P=0.001; 1 425 (450, 1 875) U, P<0.001; 600 (375, 1 425) U, P=0.020]. Similarly, average FSH costs in different ovarian response groups in the fixed-dosage group [4 725.0 (1 312.5, 6 387.5) yuan, 4 200.0 (1 312.5, 5 250.0) yuan and 1 837.5 (1 312.5, 3 947.3) yuan, respectively] were significantly lower than those in the adjusted-dosage group [6 562.5 (4 987.5, 8 028.1) yuan, P=0.001; 4 987.5 (1 575.0, 6 562.5) yuan, P<0.001; 2 100.0 (1 312.5, 4 987.5) yuan, P=0.020]. For normal-responders, the FSH cost per high-quality embryo in the fixed-dosage group [1 365.0 (875.0, 2 537.5) yuan] was significantly lower than that in the adjusted-dosage group [2 056.3 (1 268.8, 3 412.5) yuan, P<0.001]. Conclusion:FSH dosage adjustment during COS is not associated with CLBR or the incidence of OHSS. However, the fixed-dose group exhibited lower total FSH dosages and costs across different ovarian response populations. In the context of ART being covered by medical insurance, fixed FSH dosage may represent a more cost-effective ovarian stimulation protocol.

Ubiquitination represents a critical post-translational modification of proteins,capable of indu-cing alterations in the stability,cellular localisation and activity of substrate proteins.Consequently,it plays a pivotal role in a multitude of essential cellular processes.The intracellular parasite Legionella pneumophila releases in excess of 300 effector proteins into its host cell via its distinctive type IVB secre-tion system.These effector proteins regulate the physiological activity of host cells,thereby facilitating the growth and reproduction of Legionella and ultimately resulting in Legionella infection in humans.In the context of host infection,a number of effector proteins have been identified as regulators of the host cell ubiquitination system.Together with SidJ,SdjA,DupA/DupB,LnaB,and MavL,SidEs precisely and dynamically modulate the ubiquitination pathway of host cells,thereby providing a suitable environment for L.pneumophila to survive.The clarification of the biological functions of LnaB and MavL has led to the elucidation of this complex non-canonical ubiquitination regulatory cycle in L.pneumophila.This re-view presents a summary of the structural and enzymatic basis of non-classical ubiquitination mediated by SidEs,along with an examination of its biological significance in regulating endoplasmic reticulum rear-rangement and promoting Legionella-containing vacuole formation in host cells;the mechanism by which SidJ/SdjA regulates the phosphoribosylation activity of SidEs;and DupA/DupB,LnaB and MavL reverse the ubiquitination of host substrate proteins by SidEs through a multi-step catalytic reaction.In conclu-sion,this study will provide a reference for further understanding the detailed mechanism and biological significance of this type of non-classical ubiquitination modification,as well as offering insights into the pathogenic mechanism of L.pneumophila.

Objective:To evaluate the effectiveness of yttrium aluminum garnet (Nd∶YAG) laser vitreolysis in the treatment of symptomatic vitreous opacity.Methods:An observational case series study was performed.Forty-four eyes of 44 patients diagnosed as physiological vitreous opacity in Shenzhen Eye Hospital from June 2021 to September 2022 and treated with Nd∶YAG laser vitreolysis were enrolled.Before treatment and 2 months after last treatment, best corrected visual acuity (BCVA) evaluated with standard logarithmic visual acuity chart, floater areas calculated through infrared fundus photography, and objective scattering index (OSI) obtained by the Optical Quality Analysis System (OQAS) were recorded.The occurrence of complications during the follow-up period was recorded.The differences in each indicator were compared, and a simple linear regression model was used to analyze the relationship between floater area and OSI.This study adhered to the Declaration of Helsinki and was approved by the Medical Ethics Committee of Shenzhen Eye Hospital (No.2021-6-3).Patients were informed of the study methods and purposes.Written informed consent was obtained from each subject.Results:There was no significant difference in BCVA before and after Nd∶YAG laser vitreolysis ( t=-0.478, P=0.635).The floater area before laser treatment was (3.043±1.942)mm 2, which was significantly larger than (1.074±0.735)mm 2 after laser treatment ( t=0.769, P<0.001).The OSI before laser treatment was 1.976±0.975, which was significantly greater than 1.560±0.796 after laser treatment ( t=0.730, P<0.001).The results of linear regression analysis showed that the OSI=1.45+ 0.16× floater area ( F=5.681, P=0.020).No patient had visual acuity loss or intraocular pressure increase and no traumatic cataract or retinal damage occurred. Conclusions:After laser treatment, the floater area decreased, the OSI decreased, and the visual quality of patients improved.The OSI from OQAS Ⅱ and floater area can be used as quantitative evaluation indicators to objectively evaluate the effectiveness of Nd∶YAG laser vitreolysis.