BACKGROUND:BCR/ABL gene is a specific gene of Ph chromosome-positive acute lymphoblastic leukemia,and its expression level has become a sensitive indicator for monitoring minimal residual disease before and after allogeneic hematopoietic stem cell transplantation.However,whether the expression level of BCR/ABL gene before transplantation affects the efficacy of transplantation and how to guide the early intervention of relapse with tyrosine kinase inhibitors after transplantation is still inconclusive.OBJECTIVE:To explore the relationship between BCR/ABL gene expression and recurrence in patients with Ph chromosome positive acute lymphoblastic leukemia before and after related and allogeneic hematopoietic stem cell transplantation.METHODS:Twenty-four patients with Ph chromosome positive acute lymphoblastic leukemia who achieved complete hematological remission and underwent allogeneic hematopoietic stem cell transplantation were selected at the Affiliated Hospital of North China University of Science and Technology between January 2015 and December 2022.Real time fluorescence quantitative polymerase chain reaction was used to dynamically detect the expression levels of BCR/ABL genes during treatment,representing minimal residual disease.Based on BCR/ABL gene expression,tyrosine kinase inhibitors combined with chemotherapy was administered before transplantation to select the timing of allogeneic hematopoietic stem cell transplantation.After transplantation,the disease status was evaluated to guide the use of tyrosine kinase inhibitors,and an early intervention plan for recurrence was developed.RESULTS AND CONCLUSION:Follow-up was until December 2023,with a median follow-up time of 49(12-82)months.There were 8 cases of hematological recurrence,with a median recurrence time of 14(8-39)months and a cumulative recurrence rate of 33％(8/24).Univariate analysis showed that recurrence after allogeneic hematopoietic stem cell transplantation was not significantly correlated with gender,age,extramedullary complications,time from diagnosis to transplantation,HLA typing,acute graft-versus-host disease,and chronic graft-versus-host disease(P＞0.05).There was a significant correlation between the relief treatment course and minimal residual disease levels before transplantation.The second hematology completely resolution and positive minimal residual disease before transplantation had a higher hematological recurrence rate(P＜0.05).The 3-year cumulative recurrence rate,disease-free survival rate,and overall survival rate were 27％,63％,and 74％;the 5-year cumulative recurrence rate,disease-free survival rate,and overall survival rate were 38％,57％,and 74％,respectively.It is concluded that Ph chromosome positive acute lymphoblastic leukemia patients with BCR/ABL gene positive before transplantation have a higher recurrence rate.BCR/ABL gene expression after transplantation can guide the application of tyrosine kinase inhibitors and serve as a basis for early intervention in recurrence.

BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95％Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2％and a specificity of 87.6％,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1％to 92％,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.

BACKGROUND:BCR/ABL gene is a specific gene of Ph chromosome-positive acute lymphoblastic leukemia,and its expression level has become a sensitive indicator for monitoring minimal residual disease before and after allogeneic hematopoietic stem cell transplantation.However,whether the expression level of BCR/ABL gene before transplantation affects the efficacy of transplantation and how to guide the early intervention of relapse with tyrosine kinase inhibitors after transplantation is still inconclusive.OBJECTIVE:To explore the relationship between BCR/ABL gene expression and recurrence in patients with Ph chromosome positive acute lymphoblastic leukemia before and after related and allogeneic hematopoietic stem cell transplantation.METHODS:Twenty-four patients with Ph chromosome positive acute lymphoblastic leukemia who achieved complete hematological remission and underwent allogeneic hematopoietic stem cell transplantation were selected at the Affiliated Hospital of North China University of Science and Technology between January 2015 and December 2022.Real time fluorescence quantitative polymerase chain reaction was used to dynamically detect the expression levels of BCR/ABL genes during treatment,representing minimal residual disease.Based on BCR/ABL gene expression,tyrosine kinase inhibitors combined with chemotherapy was administered before transplantation to select the timing of allogeneic hematopoietic stem cell transplantation.After transplantation,the disease status was evaluated to guide the use of tyrosine kinase inhibitors,and an early intervention plan for recurrence was developed.RESULTS AND CONCLUSION:Follow-up was until December 2023,with a median follow-up time of 49(12-82)months.There were 8 cases of hematological recurrence,with a median recurrence time of 14(8-39)months and a cumulative recurrence rate of 33％(8/24).Univariate analysis showed that recurrence after allogeneic hematopoietic stem cell transplantation was not significantly correlated with gender,age,extramedullary complications,time from diagnosis to transplantation,HLA typing,acute graft-versus-host disease,and chronic graft-versus-host disease(P＞0.05).There was a significant correlation between the relief treatment course and minimal residual disease levels before transplantation.The second hematology completely resolution and positive minimal residual disease before transplantation had a higher hematological recurrence rate(P＜0.05).The 3-year cumulative recurrence rate,disease-free survival rate,and overall survival rate were 27％,63％,and 74％;the 5-year cumulative recurrence rate,disease-free survival rate,and overall survival rate were 38％,57％,and 74％,respectively.It is concluded that Ph chromosome positive acute lymphoblastic leukemia patients with BCR/ABL gene positive before transplantation have a higher recurrence rate.BCR/ABL gene expression after transplantation can guide the application of tyrosine kinase inhibitors and serve as a basis for early intervention in recurrence.

BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95％Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2％and a specificity of 87.6％,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1％to 92％,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.

Objective To explore the therapeutic effect of precise disconnection of pargastric varices guided by endoscopic ultrasound in the treatment of esophagogastric variceal bleeding.Method A retrospective analysis was conducted on 20 patients with cirrhosis esophagogastric variceal bleeding treated with endoscopic ultrasound-guided precise disconnection of pargastric varices from January 1,2024 to December 31,2024.The efficacy was analyzed.Result All 20 patients successfully completed the precise disconnection of pargastric varices under the guidance of endoscopic ultrasound.The injection of tissue gel combined with the placement of spring coils(14 cases)and the injection of tissue gel alone(4 cases)successfully blocked the pargastric varices.All patients did not experience perforation,esophageal and cardia stenosis,massive bleeding,septicemia,or ectopic embolization.One patient who received tissue gel alone had slight bleeding from the pargastric varices after surgery and improved after 3 days of treatment to reduce portal vein pressure.Another one patient who received tissue gel alone had a low-grade fever and normal body temperature after 3 days of anti-infection treatment.Conclusion Precise disconnection of pargastric varices under the guidance of endoscopic ultrasound has a good therapeutic effect on esophagogastric variceal bleeding,with fewer complications such as ectopic embolization,massive bleeding,infection,and perforation.However,close follow-up observation is still needed to address the issue of pargastric varices.

AIM:To investigate the preventive and therapeutic effects of sesamin(SES)on fatty liver disease in rats with hypertension combined with dyslipidemia,and to explore the potential mecha-nisms based on mRNA-seq.METHODS:Spontane-ously hypertensive rats(SHRs)were fed a high-fat,high-cholesterol diet to establish a rat model of hy-pertension combined with dyslipidemia,and then treated with SES for 16 weeks continuously.The ex-periment was divided into four groups:WKY,SHR,Model,and Model+SES(160 mg·kg-1·d-1).Blood pressure was measured using the tail-cuff method.Body weight was monitored,and body mass index was calculated.Liver morphology was detected by ultrasound,and liver thickness was measured.Liver wet weight was weighed,and liver index was calcu-lated.Liver volume was detected by the water dis-placement method.Serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT),aspartate amino-transferase(AST),and total bile acids(TBA)were de-tected by ELISA.Liver sequencing analysis was per-formed using mRNA-seq.Liver histomorphological changes were observed by HE staining.The degree of hepatic steatosis was observed by Oil Red O stain-ing,and the degree of hepatic fibrosis was observed by MASSON staining.The mRNA expression of Al-dh1a7,Nnmt,Irs2,Pltp,and Scd was detected by q-PCR.The protein expression of Scd,Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was detected by Western blotting.RESULTS:After 16 weeks of continuous SES administration to rats with hypertension combined with dyslipidemia,blood pressure was significantly reduced(P＜0.01),and body weight was decreased.Serum TG,TC,and LDL-C levels were decreased,while HDL-C levels were increased.Serum ALT and AST levels were decreased.Liver weight,organ in-dex,liver thickness,and liver volume were de-creased.The degree of hepatic steatosis and hepat-ic fibrosis was improved.A total of 545 differentially expressed mRNAs were identified in the livers of rats in each group,of which 278 were upregulated and 267 were downregulated.Among the 27 com-monly differentially expressed mRNAs,five mRNAs related to lipid metabolism were screened,namely Aldh1a7,Nnmt,Irs2,Pltp,and Scd.KEGG enrich-ment analysis showed that the enriched pathways were AMPK and PPAR.Further validation revealed that in the SES-treated group,the mRNA expression of Scd in the liver was decreased,while the mRNA expression of Nnmt was increased.The protein ex-pression of Scd was decreased,while the protein ex-pression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was increased.CONCLUSION:SES has preven-tive and therapeutic effects on fatty liver disease in rats with hypertension combined with dyslipidemia,and its mechanism of action may be related to the reduction of Scd expression levels in the liver and the increase in the expression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ.

Objective To explore the therapeutic effect of precise disconnection of pargastric varices guided by endoscopic ultrasound in the treatment of esophagogastric variceal bleeding.Method A retrospective analysis was conducted on 20 patients with cirrhosis esophagogastric variceal bleeding treated with endoscopic ultrasound-guided precise disconnection of pargastric varices from January 1,2024 to December 31,2024.The efficacy was analyzed.Result All 20 patients successfully completed the precise disconnection of pargastric varices under the guidance of endoscopic ultrasound.The injection of tissue gel combined with the placement of spring coils(14 cases)and the injection of tissue gel alone(4 cases)successfully blocked the pargastric varices.All patients did not experience perforation,esophageal and cardia stenosis,massive bleeding,septicemia,or ectopic embolization.One patient who received tissue gel alone had slight bleeding from the pargastric varices after surgery and improved after 3 days of treatment to reduce portal vein pressure.Another one patient who received tissue gel alone had a low-grade fever and normal body temperature after 3 days of anti-infection treatment.Conclusion Precise disconnection of pargastric varices under the guidance of endoscopic ultrasound has a good therapeutic effect on esophagogastric variceal bleeding,with fewer complications such as ectopic embolization,massive bleeding,infection,and perforation.However,close follow-up observation is still needed to address the issue of pargastric varices.

AIM:To investigate the preventive and therapeutic effects of sesamin(SES)on fatty liver disease in rats with hypertension combined with dyslipidemia,and to explore the potential mecha-nisms based on mRNA-seq.METHODS:Spontane-ously hypertensive rats(SHRs)were fed a high-fat,high-cholesterol diet to establish a rat model of hy-pertension combined with dyslipidemia,and then treated with SES for 16 weeks continuously.The ex-periment was divided into four groups:WKY,SHR,Model,and Model+SES(160 mg·kg-1·d-1).Blood pressure was measured using the tail-cuff method.Body weight was monitored,and body mass index was calculated.Liver morphology was detected by ultrasound,and liver thickness was measured.Liver wet weight was weighed,and liver index was calcu-lated.Liver volume was detected by the water dis-placement method.Serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT),aspartate amino-transferase(AST),and total bile acids(TBA)were de-tected by ELISA.Liver sequencing analysis was per-formed using mRNA-seq.Liver histomorphological changes were observed by HE staining.The degree of hepatic steatosis was observed by Oil Red O stain-ing,and the degree of hepatic fibrosis was observed by MASSON staining.The mRNA expression of Al-dh1a7,Nnmt,Irs2,Pltp,and Scd was detected by q-PCR.The protein expression of Scd,Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was detected by Western blotting.RESULTS:After 16 weeks of continuous SES administration to rats with hypertension combined with dyslipidemia,blood pressure was significantly reduced(P＜0.01),and body weight was decreased.Serum TG,TC,and LDL-C levels were decreased,while HDL-C levels were increased.Serum ALT and AST levels were decreased.Liver weight,organ in-dex,liver thickness,and liver volume were de-creased.The degree of hepatic steatosis and hepat-ic fibrosis was improved.A total of 545 differentially expressed mRNAs were identified in the livers of rats in each group,of which 278 were upregulated and 267 were downregulated.Among the 27 com-monly differentially expressed mRNAs,five mRNAs related to lipid metabolism were screened,namely Aldh1a7,Nnmt,Irs2,Pltp,and Scd.KEGG enrich-ment analysis showed that the enriched pathways were AMPK and PPAR.Further validation revealed that in the SES-treated group,the mRNA expression of Scd in the liver was decreased,while the mRNA expression of Nnmt was increased.The protein ex-pression of Scd was decreased,while the protein ex-pression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ was increased.CONCLUSION:SES has preven-tive and therapeutic effects on fatty liver disease in rats with hypertension combined with dyslipidemia,and its mechanism of action may be related to the reduction of Scd expression levels in the liver and the increase in the expression of Nnmt,AMPK,p-AMPK,PPARα,and PPARγ.

Objective To isolate endophytic fungi from Angelica sinensis and evaluate the bioactivity of their secondary metabolites.Methods Angelica sinensis and rhizosphere soil were utilized as materials.The tissue homogenization method was employed with six diverse culture media to isolate endophytic fungi.The antibacterial activity of secondary metabolites was gauged using a 96-well plate assay,while UV spectrophotometry was used to evaluate the inhibitory activity of four enzymes.Results A total of 153 fungal strains were isolated and purified from Angelica sinensis roots,stems,leaves,and soil.The samples exhibited specific inhibitory activities against adenosine deaminase(ADA),β-lactamase,xanthine oxidase(XO),and tyrosinase(TYR),with rates of 45.83%,52.78%,51.39%and 55.56%,respectively.Furthermore,1.39%of the samples displayed wide-ranging inhibitory effects against four indicator bacteria.Strain 6B also showcased the lowest inhibitory concentration values of 62.5 and 7.81 μg/mL against Escherichia coli ATCC25922 and ATCC35218,respectively,signifying its potential research significance.Conclusion Angelica sinensis has abundant endophytic fungal resources and is a good source for discovering active compounds,demonstrating certain research value.

ObjectiveBased on non-targeted metabolomics， to analyze the regulation of endogenous differential metabolites in serum of type 2 diabetes mellitus（T2DM） rats by Fuling Yunhua granules， and to clarify the metabolic pathways through which this granules exerted its effect on improving T2DM. MethodSeventy SD rats， half male and half female， were randomly divided into the control group， model group， and high， medium， low dose groups of Fuling Yunhua granules（20.70， 10.35， 5.18 g·kg^-1 in raw drug amount） and the positive drug group（pioglitazone hydrochloride tablets， 8.1 mg·kg^-1）. Except for the control group， other groups were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin（STZ） to establish a T2DM rat model. After successful modeling， the treatment groups were administered the corresponding drugs by gavage， and the control group and model group were treated with an equal volume of saline by gavage， once/d， for 28 d. Fasting blood glucose（FBG） and glycosylated hemoglobin A1c（GHbA1c） levels were measured in all groups of rats during the administration period， and hematoxylin-eosin（HE） staining was used to observe the pathomorphological changes in the pancreatic tissues of rats at the end of the administration period. The endogenous metabolite levels in rat serum were detected by ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-LTQ-Orbitrap MS）， and the data were processed using principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Differential metabolites were identified by the Human Metabolome Database（HMDB） and the Kyoto Encyclopedia of Genes and Genomes（KEGG）， and screened for differential metabolites with variable importance in the projection（VIP） value>1， P<0.05， and fold change（FC）<0.6 or FC>1. And the metabolic pathway enrichment analysis of the screened differential metabolites was performed by MetaboAnalyst 5.0， then the screened differential metabolites were diagnosed and evaluated by the receiver operating characteristic（ROC） curves. ResultCompared with the control group， the FBG level of rats in the model group increased significantly（P<0.01）， the GHbA1c content tended to increase， but the difference was not statistically significant， and the pancreatic tissue of rats was obviously damaged， the number of pancreatic islets decreased， and the pancreatic β-cells were obviously reduced， atrophied and enlarged. Compared with the model group， the FBG levels of rats in the high dose group of Fuling Yunhua granules and the positive drug group were significantly reduced after 2 weeks of administration（P<0.05， P<0.01）， the GHbA1c content of rats in the high dose group of Fuling Yunhua granules was significantly reduced（P<0.05）， and the pancreatic tissue lesions of rats in the different dose groups of Fuling Yunhua granules were reduced. The results of non-targeted metabolomics showed that 46 differential metabolites were significantly changed in the model group compared with the blank group. Pathway enrichment analysis found that T2DM mainly affected biological processes including biosynthesis of primary bile acid， D-amino acid metabolism， steroid hormone biosynthesis， and glycerophospholipid metabolism in rats. Compared with the model group， the levels of 8 differential metabolites in the high dose group of Fuling Yunhua granules were significantly adjusted， and the pathway enrichment analysis found that D-amino acid metabolism， retinol metabolism， glycine， serine and threonine metabolism， tryptophan metabolism and other metabolic pathways were mainly involved. ROC curves further analysis revealed that the four characteristic differential markers of 11-cis-retinol， D-piperidinic acid， D-serine， and p-cresol sulfate had high diagnostic value for the treatment of T2DM with Fuling Yunhua granules. ConclusionFuling Yunhua granules can improve the symptoms of T2DM rats by regulating the amino acid metabolic and retinol metabolic pathways through the modulation of endogenous differential metabolites.