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: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.

OBJECTIVE To investigate the effects and potential mechanism of Yiqi wenyang huwei decoction （YQWY） in improving airway inflammation and remodeling in rats with bronchial asthma （BA） based on the Toll-like receptor 4 （TLR4）/myeloid differentiation primary response protein 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Male SD rats were randomly divided into the normal group， the model group， the dexamethasone group （positive control， 0.5 mg/kg）， and YQWY low-， medium- and high-dose groups （5， 10， 20 g/kg， calculated by the crude drug）， with 8 rats in each group. Except for the normal group， rats in all other groups were sensitized twice with ovalbumin combined with aerosol challenge to establish a BA model. From day 14 to day 34 of the experiment， the rats in each group were administered the corresponding drug solution or normal saline intragastrically， once a day， 1 hour before aerosol challenge. At 24 hours after the final aerosol challenge， asthma symptom scores were assessed， serum levels of immunoglobulin E （IgE） were measured， and the levels of inflammatory cytokines （interleukin-4， interleukin-5， interleukin-13 and tumor necrosis factor-α） and the numbers of inflammatory cells （white blood cell， eosinophil， neutrophil， lymphocyte， monocyte and basophil） in bronchoalveolar lavage fluid were determined. Pathological changes in lung tissue were observed. The mRNA expressions of TLR4， MyD88 and NF-κB， as well as the protein expressions of TLR4， MyD88， NF-κB p65 and phosphorylated NF-κB p65 in lung tissue， were detected. RESULTS Compared with the model group， the pathological changes， such as inflammatory cell infiltration， abnormal deposition of collagen fibers， and goblet cell hyperplasia in the lung tissue of rats in each drug group， were alleviated to varying degrees. The asthma symptom scores （except for the YQWY low-dose group）， the levels of IgE and inflammatory cytokines （except for interleukin-5 in the YQWY medium-dose group）， the number of inflammatory cells （except for monocyte and basophil in the YQWY low-dose group）， the mRNA expression of TLR4， MyD88 and NF-κB， as well as the protein expressions of TLR4， MyD88， NF-κB p65 and phosphorylated NF-κB p65 （except for MyD88 and NF-κB p65 proteins in the YQWY low-dose group as detected by Western blo t） were all significantly reduced or down-regulated （ P ＜0.05 or P ＜0.01）. CONCLUSIONS YQWY can alleviate asthma-like manifestations in BA rats and improve their airway inflammation and remodeling； these effects may be related to the formula’s inhibition of the abnormal activation of the TLR4/MyD88/NF-κB signaling pathway.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

BACKGROUND:Titanium implants are widely used in clinical practice because of their high strength and good biocompatibility.However,during implantation,bacterial infection and tissue damage environment produce a large number of reactive oxygen species,which can easily lead to delayed tissue healing and surgical failure.Consequently,the development of titanium implants with antimicrobial and antioxidant properties becomes paramount. OBJECTIVE:Considering the potent antimicrobial attributes of copper ions and the remarkable antioxidant qualities of polyphenols,we proposed the fabrication of polyphenol-mediated copper ion coatings on titanium surfaces.These coatings were subsequently assessed for their in vitro antimicrobial and antioxidant properties. METHODS:Nanostructures were generated on the titanium surface using the alkali thermal method.The titanium was immersed in a solution containing tannic acid and copper ions to achieve polyphenol-mediated copper ion coatings.The surface morphology and water contact angle were detected.The loading and release of copper ions were examined using atomic absorption spectroscopy.Staphylococcus aureus was inoculated on the surface of pure titanium sheet(blank group),alkali heat treated titanium sheet(control group),and polyphenol mediated copper ion modified titanium sheet(experimental group)to observe the bacterial survival status.Osteoblast precursor cells MC3T3-E1 were co-cultivated on the surface of three groups of titanium sheets to assess their antioxidant properties and bioactivity. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the polyphenol-mediated copper ion modified titanium sheet had rod-like nanostructures and no cracks on the surface.The surface hydrophilicity of copper ion modified titanium sheet mediated by polyphenol was close to that of pure titanium sheet.Atomic absorption spectrometry results showed a 51%increase in the loading capacity of copper ions after polyphenol mediation,with a uniform release of copper ions.(2)The antibacterial rates of titanium sheets in the blank group,control group,and experimental group were 0%,21.65%,and 93.75%,respectively.The live/dead staining and CTC staining showed that the live bacteria on the surface of titanium plates in the blank group were the most,and the live bacteria on the surface of titanium plates in the experimental group were the least.(3)The results of live/dead staining and CCK-8 assay showed that the three groups of titanium sheets had good cytocompatibility,and the titanium sheets in the experimental group were more conducive to the proliferation of MC3T3-E1 cells.Active oxygen fluorescence probe detection exhibited that compared with the other two groups,the fluorescence intensity of active oxygen on the surface of the experimental group was significantly reduced.The results of alkaline phosphatase and alizarin red S staining showed that the osteogenic differentiation and extracellular matrix mineralization of MC3T3-E1 cells on the surface of titanium sheets in the experimental group were stronger than those in the other two groups.(4)These results show that the polyphenol-mediated copper ion coating has strong antibacterial and antioxidant properties and promotes osteogenic differentiation.

BACKGROUND: Tissue engineering holds promise for vascular repair and regeneration by mimicking the extracellular matrix of blood vessels. However, achieving a functional and thick vascular wall with aligned fiber architecture by electrospinning remains a significant challenge. METHODS: A novel electrospinning setup was developed that utilizes an auxiliary electrode and a spring. The impact of process parameters on fiber size and morphology was investigated. The structure and functions of the scaffolds were evaluated through material characterization and assessments of cellular biocompatibility. RESULTS: The new setup enabled controlled deposition of fibers in different designed orientations. The fabricated small-diameter vascular scaffolds consisted of an inner layer of longitudinally oriented fibers and an outer layer of circumferentially oriented fibers (L + C vascular scaffold). Key parameters, including rotational speed, the utilization of the auxiliary electrode, and top-to-collector distance (TCD) significantly influenced fiber orientation. Additionally, voltage, TCD, feed rate, needle size, auxiliary electrode and collector-auxiliary electrode distance affected fiber diameter and distribution. Mechanical advantages and improved surface wettability of L + C vascular scaffold were confirmed through tensile testing and water contact angle. Cellular experiments indicated that L + C vascular scaffold facilitated cell adhesion and proliferation, with human umbilical vein endothelial cells and smooth muscle cells attaching and elongating along the fiber direction of the inner and outer layer, respectively. CONCLUSION This study demonstrated the feasibility of fabricating fiber-aligned, thick-walled vascular scaffolds using a modified electrospinning setup. The findings provided insights into how the auxiliary electrode, specific collector influenced fiber deposition, potentially advancing biomimetic vascular scaffold engineering.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Objective To survey the free influenza vaccination status and willingness among the elderly in Deqing County,Zhejiang Province,and analyze the influencing factors.Methods Based on population data and the electronic medical system of Deqing County,the influenza vaccine coverage from 2018 to 2022 after the implementation of the free influenza vaccination policy was calculated.A proportional stratified random sampling method was used to select elderly individuals aged 60 and above from six streets/towns in Deqing County.A questionnaire survey was conducted to assess influenza vaccination behaviors from 2020 to 2022 and vaccination willingness for the 2023 influenza season.The chi-square test and logistic regression were used to analyze potential factors associated with vaccination behavior and subsequent willingness among the elderly.Results An average of influenza vaccines for the elderly per year were 56.2 thousand,with influenza vaccination coverage rate of 46.16%in average over the five years.Among 729 subjects,the vaccination rate increased from 69.3%in 2020 to 75.3%in 2022,and 81.9%of them were willing to receive influenza vaccines in the next flu season.Logistic regression analysis revealed that individuals with agricultural household registration(OR=3.05,95%CI:1.82-8.99),lower education levels(OR=2.82,95%CI:1.15-6.93),awareness of the free vaccine policy(OR=4.65,95%CI:1.82-11.91),and belief in vaccine efficacy(OR=6.61,95%CI:3.20-13.61)had higher vaccination rates.Factors associated with a more positive vaccination willingness included an annual household income of<150 thousand CNY(OR=1.65,95%CI:1.04-2.60),awareness of the free vaccine policy(OR=3.07,95%CI:1.84-5.12),perceived vaccine efficacy(OR=4.39,95%CI:2.77-6.96),and perceived vaccine safety(OR=1.57,95%CI:1.01-2.43).The main reasons for non-vaccination were concerned about the side effects of the vaccine(37.9%),thoughts that they were in good health and did not need to be vaccinated(30.3%),and influenza vaccines were ineffective(21.2%).The main reasons for vaccination were to protect themselves(89.1%),vaccination was free(65.5%)and to protect their families(60.6%).Conclusion The elderly in Deqing County had a relatively high influenza vaccination rate and follow-up vaccination willingness rate,but there still existed a gap to reach at target rate recommended by WHO.The local government should strengthen health education related to influenza vaccine knowledge,and publicize free vaccination policy to improve the vaccination rate and willingness in next season.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective:To evaluate the anti-reflux effect of digestive tract reconstruction using esophageal-tubular gastric asymmetric anastomosis after radical resection of esophageal and esophagogastric junction cancer.Methods:The main steps were as follows:(1)oblique incision of the lower esophagus;(2)curved incision of the tubular anterior gastric wall;(3)the lower end of the esophagus was anastomosed to the tubular gastric incision with a 90-degree torsion; (4)The anterior wall of the anastomosis was reinforced with a transverse-inverted suture,the posterior wall with a folded suture,and the corners of the gastric stump were buried with sutures.The anastomosis operation time,postoperative complications and postoperative hospital stay were recorded;the reconstructed structure and anti-reflux effect of the anastomosis were observed by digestive tract radiography,gastroscopy and follow-up investigation.Results:The Department of Gastrointestinal and Thoracic Surgery of Huaian First People's Hospital, affiliated to Nanjing Medical University, treated 5 patients of esophagogastric junction cancer and 20 esophageal cancer cases between August 2022 and November 2024, including 19 men and 6 women, with a mean age of (66.7±7.4) years. The mean anastomosis time was (35.4±5.9) minutes, the intraoperative blood loss was (117.6±33.4) ml and the mean postoperative hospital stay was(16.6±5.2) days, with no complications such as anastomotic leakage and bleeding. Postoperative digestive tract radiography (Trendelenburg position)showed that all the patients had no contrast reflux,gastroscopy showed no signs of reflux esophagitis and bile reflux gastritis, the anastomosis showed an inverted whiskers valve-like structure. The median follow-up time was (16.8±6.3) months, and all patients had no reflux symptoms such as acid reflux and belching,and no acid suppressive medication was needed.Conclusion:The esophageal-tubular gastric asymmetric anastomosis is a safe and effective antireflux reconstruction technique.