Objective To explore the role of neogambogic acid in the characteristics of colorectal cancer stem cells (CRC-CSCs) through the Wnt/β-catenin signaling pathway. Methods The colorectal cells SW480 and HCT166 were divided into control group and neogambogic acid groups (1.5, 3, 6, and 12 μmol/L). The viability of CRC-CSCs was determined by MTT method, and spheroid and clone formation assays were used to assess the capacity of spheroid formation and self-renewal ability of the cells. The effects of neogambogic acid on the apoptosis and cell cycle of CRC-CSCs were evaluated by flow cytometry assays. Real-time quantitative PCR was used to detect the mRNA expression levels of relative markers (CD133, CD44, ALDH1, Oct4, and Nanog) of CRC-CSCs, and the protein expression levels of the self-renewal marker (PCNA), apoptosis markers (cleaved caspase-3 and cleaved caspase-9), and Wnt/β-catenin signaling pathway markers (p-GSK3β, GSK3β, β-catenin, and Wnt) were analyzed using Western blot. Results Compared with the control group, after neogambogic acid treatment, the viability of SW480 and HCT116 cells decreased (P<0.05), the spheroid forming ability and the clone numbers of CRC-CSCs decreased (P<0.001, P<0.01) but the cell apoptosis rate increased (P<0.01), and cell cycle was arrested in G₀/G₁ phase. Moreover, neogambogic acid downregulated the mRNA and protein expression of relative markers of CRC-CSCs (CD133, CD44, ALDH1, Oct4, and Nanog), PCNA, p-GSK3β, β-catenin, and Wnt (P<0.05) and upregulated the expression of cleaved caspase-3, cleaved caspase-9, and GSK3β (P<0.01). Conclusion Neogambogic can inhibit the stem cell properties of colorectal cells via inhibition of Wnt/β-catenin signaling pathway. As a result, neogambogic acid may be an attractive agent against colorectal cancer.

Objective To analyze the clinical outcomes of early invasive fungal disease(IFD)in patients after allogenetic hematopoietic stem cell transplantation(allo-HCST)with metagenomic next-generation sequencing(mNGS).Methods A retrospective analysis was conducted on patients undergoing allo-HCST in our Bone Marrow Transplantation Center between July 2021 and October 2022.These patients experienced one of the following conditions within 100 d after transplantation:① Patients with persistent fever and negative blood culture after empiric antimicrobial therapy for 72 h or longer;② Hyperpyrexia of unknown origin occurred again after effective anti-infection in the past;③ Symptoms in lower respiratory tract associated with lung lesions on CT scan,and empiric anti-infective therapy was ineffective.Peripheral blood or bronchoscopic alveolar lavage fluid were tested with mNGS,and overall survival(OS)and non-relapse mortality(NRM)were analyzed.Results There were 60 patients enrolled in this study.For the peripheral blood samples of 47 cases and bronchoalveolar lavage fluid samples of 13 cases,mNGS found that 19 cases were negative to pathogens,30 cases were non-fungal positive,and 11 case were fungal positive,including 3 cases of aspergillus,5 cases of mucor,2 cases of Candida tropicalis,and 1 case of Trichosporon asahii.Of the 11 patients with fungal positive,8 achieved complete remission after antifungal therapy according to the mNGS results.The 1-year OS and NRM of the 60 patients were 70.0％(95％CI:64.1％～75.9％)and 20.0％(95％CI:11.9％～32.5％),respectively,while those of the fungal infection patients were 54.5％(95％CI:49.5％～69.5％)and 36.4％(95％ CI:15.5％～70.3％),respectively.No significant differences were seen in 1-year OS(P=0.487)and 1-year NRM(P=0.358)among the negative,fungal infection and non-fungal infection patients,neither OS(P=0.238)and NRM(P=0.154)between the fungal infection and the non-fungal infection patients.Conclusion mNGS can rapidly diagnose the early IFD after allo-HSCT,which is helpful for timely and effective treatment and improves the prognosis of patients.

Objective To construct risk prediction models of death or readmission in patients with acute heart failure(AHF)during the vulnerable phase based on machine learning algorithms and screen the optimal model.Methods A total of 651 AHF patients with admitted to Department of Cardiology of the Second Affiliated Hospital of Army Medical University from October 2019 to July 2021 were included.The clinical data consisting of admission vital signs,comorbidities and laboratory results were collected from electronic medical records.The composite endpoint was defined as all-cause death or readmission for worsening heart failure within 3 months after discharge.The patients were divided into a training set(521 patients)and a test set(130 patients)in a ratio of 8:2 through the simple random sampling.Six machine learning models were developed,including logistic regression(LR),random forest(RF),decision tree(DT),light gradient boosting machine(LGBM),extreme gradient boosting(XGBoost)and neural networks(NN).Receiver operating characteristic(ROC)curve and decision curve analysis(DCA)were used to evaluate the predictive performance and clinical benefit of the models.Shapley additive explanation(SHAP)was used to explain and evaluate the effect of different clinical characteristics on the models.Results A total of 651 AHF patients were included,of whom 203 patients(31.2%)died or were readmitted during the vulnerable phase.ROC curve analysis showed that the AUC values of the LR,RF,DT,LGBM,XGBoost and NN model were 0.707,0.756,0.616,0.677,0.768 and 0.681,respectively.The XGBoost model had the highest AUC value.DCA showed that the XGBoost model exhibited greater clinical net benefit compared with other models,with the best predictive performance.SHAP algorithm analysis showed that the clinical features that had the greatest impact on the output of the model were serum uric acid,D-dimer,mean arterial pressure,B-type natriuretic peptide,left atrial diameter,body mass index,and New York Heart Association(NYHA)classification.Conclusion The XGBoost model has the best predictive performance in predicting the risk of death or readmission of AHF patients during the vulnerable phase.

BACKGROUND:Superior lower limb mobility is regarded as one of the prerequisites for winning competitions.Wearable resistance training can effectively overcome the deficiency in the transfer efficiency of traditional strength training in enhancing lower limb mobility.Considering that the impact of wearable resistance training based on different body parts on lower limb mobility may have significant differentiated characteristics,it is particularly important to review and summarize the specific application strategies and acute and chronic intervention effects. OBJECTIVE:To comb and analyze acute and chronic intervention effects of wearable resistance training based on different body parts on lower limb mobility,in order to provide insightful and methodological references for optimizing application strategies for lower limb movement ability. METHODS:A literature search was conducted in CNKI,Wanfang,VIP,Web of Science,Medline,SPORTDiscus,and PubMed databases for publications up to October 2023.Chinese and English search terms were"arm,forearm,limb,leg,lower extremity,vest,trunk,resist,weight,load,sprint,agility,change of direction".A total of 60 articles were ultimately included for review after screening the retrieval results. RESULTS AND CONCLUSION:(1)Trunk loading of 6-20%of body mass is suitable for optimizing acceleration in sprinting,while trunk loading of≤6%body mass is suitable for optimizing high-speed running.A trunk load of 5%body mass is applicable for optimizing change-of-direction movement;forearm,calf,or thigh loading often uses 1%or 2%body mass.(2)Trunk loading optimizes the functional performance of the lower limb stretch-shortening cycle by increasing vertical load.This enhances the efficiency of ground reaction force utilization and strengthens the coordinated stability control of the whole body musculature.Forearm loading effectively enhances the driving force of the upper limb swing,improves the propulsive force of the lower limb sprint,and optimizes the efficiency of inter-limb coordination.Calf loading can impose restrictions on the function of the hip joint,thereby leading to localized load stimulation and compensatory functional enhancement in the knee or ankle joint.Thigh loading partially restricts the peak extension angle and speed of the knee joint,creates specific load stimulation at the hip joint,and significantly improves its rotational kinetic energy output.(3)During larger-angle change-of-direction movements,the impact of calf loading is more significant than thigh loading.Thigh loading stimulation helps to enhance power output,while calf loading stimulation aids in improving stability control and directional change.(4)Currently,wearable resistance training has been proven to be an effective way to improve sprint and change-of-direction performance.The methodological strategies to improve sprint performance are relatively mature,but the optimal application scheme to improve change-of-direction performance needs to be further refined and optimized.Further research is recommended to supplement this area.

Objective To investigate the effects of intraoperative application of esketamine on post-operative anxiety and depression in burn patients undergoing escharectomy and skin grafting.Methods Seventy-three patients undergoing escharectomy and skin grafting were selected,46 males and 27 females,aged 18-64 years,BMI 18.5-27.9 kg/m2,ASA physical status Ⅱ or Ⅲ.According to the random number table method,the patients were divided into two groups:esketamine group(group E,n=37)and control group(group C,n=36).Group E received a 0.2 mg/kg intravenous bolus of esketamine during anesthesia induction followed by a 0.1 mg·kg-1·h-1 continuous infusion until the end of surgery.Group C received an equal volume of normal saline.Patients in both groups received patient-controlled intravenous analgesia(PCIA)after surgery.The postoperative eye opening time,extubation time,PACU residence time,hospitalization and the number of effective compressions and total compressions of postoperative anal-gesia pumpand remediate analgesia after surgery were recorded.The self-rating anxiety scale(SAS),self-rating depression scale(SDS)and incidence of anxiety and depression were recorded 1 day before surgery,3 and 7 days after surgery.The occurrence of adverse reactions within 48 hours after surgery were also recor-ded.Results Compared with group C,the postoperative PACU residence time and hospitalization in group E were shortened(P＜0.05),the times of effective and total compressions and remediate analgesia after surgery in group E were decreased(P＜0.05),the scores of SAS and SDS and incidence of anxiety and depression at 3 and 7 days after surgery in group E were decreased(P＜0.05).There were no statistical differences in adverse reactions within 48 hours after surgery between the two groups.Conclusion Intraop-erative application of esketamine in burn patients undergoing escharectomy and skin grafting can improve postoperative anxiety and depression,reduce the usage of postoperative opioids and promote early recovery.

OBJECTIVE In the process of drug dispensing, using computer vision technology to identify drugs is vulnerable to the influence of lighting, angle, packaging and other factors, which will produce large identification errors. Therefore, this paper proposes an object detection algorithm for drug appearance recognition(YOLOv4-GhostNet-CMB). METHODS Firstly, the algorithm redesigned the backbone feature extraction network in YOLOv4 by using GhostNet. Secondly, the CA attention model was brought into the Ghost module, aggregate features along horizontal and vertical directions to enhance the precise positioning of drugs. Finally, Bi-FPN feature pyramid structure was introduced to connect with the new backbone, and added a feature graph output which could enhance feature extraction and improved the detection accuracy of drugs. RESULTS The experimental results show that the average detection accuracy of YOLOv4-GhostNet-CMB algorithm reached 92.24%, which was a significant improvement of 4.49% compared with YOLOv4 algorithm in term of detection accuracy. CONCLUSION The model size is only 150 MB, nd this algorithm can effectively identify drugs.

Objective To investigate the efficacy and safety of microwave ablation(MWA)versus hepatic resection(HR)in the treatment of hepatocellular carcinoma(HCC)with liver cirrhosis using a meta-analysis.Methods This study was conducted according to the PRISMA guideline,with a PROSPERO registration number of CRD42024509185.PubMed,the Cochrane Library,EMBASE,Web of Science,CNKI,VIP,and Wanfang Data were searched for randomized controlled trials(RCTs)and cohort studies on MWA versus HR in the treatment of HCC with liver cirrhosis published up to November 2023,and Stata 12.0 was used to perform the meta-analysis.Results A total of 3 RCTs and 5 retrospective cohort studies were included,with 953 patients in total.The meta-analysis showed that there were no differences between MWA and HR in 1-,2-,3-,and 5-year overall survival(OS)rates(all P>0.05)and 1-,2-,and 5-year recurrence rates(all P>0.05).Compared with HR,MWA had a significantly higher 3-year recurrence rate(risk ratio[RR]=1.59,95%confidence interval[CI]:1.08-2.33,P=0.017)and significantly lower 1-,3-,and 5-year disease-free survival(DFS)rates(1-year DFS rate:RR=0.94,95%CI:0.89-0.99,P=0.018,I2=0.0%;3-year DFS rate:RR=0.84,95%CI:0.72-0.98,P=0.023,I2=25.4%;5-year DFS rate:RR=0.75,95%CI:0.58-0.98,P=0.032,I2=34.6%).However,subgroup analysis showed that there were no significant differences between MWA and HR in 1-,2-,and 3-year OS rates and 1-and 3-year DFS rates in the RCT subgroup(all P>0.05).Compared with HR,MWA had significantly better intraoperative blood loss(standardized mean difference[SMD]=-2.31,95%CI:-2.64 to-1.97,P<0.001,I2=3.1%),time of operation(SMD=-3.38,95%CI:-4.05 to-2.71,P<0.001,I2=73.8%),length of hospital stay(SMD=-2.54,95%CI:-3.27 to-1.80,P<0.001,I2=92.8%),adverse reactions(RR=0.42,95%CI:0.30-0.59,P<0.001,I2=0.0%),and liver function(SMD=-1.43,95%CI:-1.89--0.97,P<0.001).Conclusion There are no significant differences between MWA and HR in local recurrence,DFS,and OS,but MWA tends to have a less intraoperative blood loss,a shorter time of operation,fewer adverse reactions,a less impact on liver function,and a shorter length of hospital stay.

Objective To evaluate the efficacy of a modified sericin hydrogel scaffold loaded with dexamethasone(SMH-CD/DEX)scaffold for promoting bone defect healing by stimulating anti-inflammatory macrophage polarization.Methods The light-curable SMH-CD/DEX scaffold was prepared using dexamethasone-loaded NH2-β-cyclodextrin(NH2-β-CD)and sericin hydrogel and characterized by scanning electron microscopy(SEM),Fourier transform infrared spectroscopy(FTIR),biocompatibility assessment and drug release test.THP-1 macrophages incubated with the scaffold were examined for protein expressions of iNOS and Arg-1,mRNA expressions of IL-6,Il-10,Arg-1 and iNOS,and surface markers CD86 and CD206 using Western blotting,RT-qPCR,and flow cytometry.In a co-culture system of human periodontal ligament stem cells(HPDLSCs)and THP-1 macrophages,the osteogenic ability of the stem cells incubated with the scaffold was evaluated by detecting protein expressions of COL1A1 and Runx2 and expressions of ALP,Runx2,OCN and BMP2 mRNA,ALP staining,and alizarin red staining.In a rat model of mandibular bone defect,the osteogenic effect of the scaffold was assessed by observing bone regeneration using micro-CT and histopathological staining.Results In THP-1 macrophages,incubation with SMH-CD/DEX scaffold significantly enhanced protein expressions of Arg-1 and mRNA expressions of IL-10 and Arg-1 and lowered iNOS protein expression and IL-6 and iNOS mRNA expressions.In the co-culture system,SMH-CD/DEX effectively increased the protein expressions of COL1A1 and Runx2 and mRNA expressions of ALP and BMP2 in HPDLSCs and promoted their osteogenic differentiation.In the rat models,implantation of SMH-CD/DEX scaffold significantly promoted bone repair and bone regeneration in the bone defect.Conclusion The SMH-CD/DEX scaffold capable of sustained dexamethasone release promotes osteogenic differentiation of stem cells and bone defect repair in rats by regulating M2 polarization.

Objective To analyze the core functional component groups(CFCG)in Yinchenhao Decoction(YCHD)and their possible pathways for treating hepatic fibrosis based on network pharmacology.Methods PPI data were extracted from DisGeNET,Genecards,CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1.The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction.A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets.In cultured human hepatic stellate cells(LX-2 cells),the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay;the effects of these compounds on collagen α1(Col1a1)mRNA expression and the pathways in 20 ng/mL TGF-β1-stimulated cells were analyzed using RT-qPCR and Western blotting.Results A total of 1005 pathogenic genes,226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained.Benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid were selected for CCK-8 verification,and they all showed minimal cytotoxicity below the concentration of 200 μmol/L.Clorius,polydatin,lauric acid and ferulic acid all effectively inhibited TGF-β1-induced LX-2 cell activation.At the concentration of 200 μmol/L,all these 4 components inhibited PI3K,p-PI3K,AKT,p-AKT,ERK,p-ERK,P38 MAPK and p-P38 MAPK expressions in TGF-β1-induced LX-2 cells.Conclusion The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid,which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.

Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) .Methods:In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed.Results:A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively ( P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively ( P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively ( P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively ( P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively ( P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively ( P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively ( P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively ( P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively ( P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion:There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.