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 analyze the risk factors of enteral nutrition intolerance in elderly patients with severe pneumonia(SP)in intensive care unit(ICU)and construct its prediction model.Methods A total of 140 elderly patients with severe pneumonia in ICU ward of the First Affiliated Hospital of Ningbo University from January 2021 to December 2022 were selected.According to the tolerance of enteral nutrition,they were divided into tolerance group(n=82)and intolerance group(n=58).Univariate and multivariate Logistic regression analysis was used to analyze the risk factors of enteral nutrition intolerance in elderly patients with severe pneumonia in ICU.The risk prediction model was constructed,and the receiver operating characteristic(ROC)curve was drawn to evaluate the prediction effect of the model.Results Multivariate Logistic regression analysis showed that acute gastrointestinal injury(AGI),intra-abdominal pressure(IAP),and the use of antibiotics≥2 were independent influencing factors of enteral nutrition intolerance in elderly patients with severe pneumonia in ICU(P<0.05).The Hosmer-Lemeshow goodness-of-fit test was used to evaluate the fitting effect of the equation.The area under the curve was 0.867(95%CI:0.750-0.984),the sensitivity was 87.8%,and the specificity was 85.1%.Conclusion The risk prediction model constructed in this study can effectively predict the risk of enteral nutrition intolerance in elderly patients with severe pneumonia in ICU.

Objective To investigate the relationships of serum levels of human fractalkine (CX3CL1) and chitinase-3-like protein 1 (YKL-40) with early cognitive impairment in elderly patients with Alzheimer's disease (AD). Methods A total of 110 AD patients in the Second Affiliated Hospital of Xinxiang Medical University from February 2021 to December 2023 were selected as AD group, and 50 healthy individuals with physical examination during the same period were selected as control group. Clinical materials and serum levels of CX3CL1 and YKL-40 were compared between the two groups, and multivariate Logistic regression models were used to analyze the influencing factors of cognitive impairment in AD patients. Based on the Mini-Mental State Examination (MMSE) score, the 110 AD patients were divided into mild cognitive impairment group (n=47), moderate cognitive impairment group (n=36), and severe cognitive impairment group (n=27). Spearman correlation analysis was performed to explore the relationships of serum CX3CL1 and YKL-40 with MMSE score, Addenbrooke's Cognitive Examination-Ⅲ (ACE-Ⅲ) score, and Montreal Cognitive Assessment (MoCA) score. Results The AD group had higher proportions of patients aged over 80 years, with an education level of primary school or below, smoking history, alcohol consumption history, diabetes mellitus, hypertension, AD family history, and living alone as well as higher serum levels of CX3CL1 and YKL-40 compared to the control group; conversely, the AD group had a lower proportion of patients engaging in no physical exercise/labor, and lower MMSE, ACE-Ⅲ, and MoCA scores, with significant between-group differences (P < 0.05). Advanced age, diabetes mellitus, and high serum levels of CX3CL1 and YKL-40 were independent risk factors for cognitive impairment in AD patients (P < 0.05), while an education level of college or above was a protective factor (P < 0.05). Compared with the mild cognitive impairment group, the moderate and severe cognitive impairment groups had higher serum levels of CX3CL1 and YKL-40, and the severe cognitive impairment group had higher serum levels of CX3CL1 and YKL-40 than the moderate group, with significant between-group differences (P < 0.05). Spearman correlation analysis revealed that serum CX3CL1 and YKL-40 were negatively correlated with MMSE, ACE-Ⅲ, and MoCA scores (P < 0.05). Conclusion Serum CX3CL1 and YKL-40 are highly expressed in elderly AD patients, and are closely related to early cognitive impairment in elderly AD patients.

Objective:To investigate the value of mDixon-Quant imaging combined with blood cell parameters in assessing lymphovascular invasion (LVI) and lymph node metastasis (LNM) in rectal cancer (RC). Methods:Clinical and magnetic resonance imaging (MRI) data were retrospectively collected from 62 patients with pathologically confirmed RC at North China University of Science and Technology Affiliated Hospital from November 2022 to June 2024. We calculated the ratio of blood cell parameters and measured the mDixon-Quant parameters,including fat fraction (FF),R2* value,and T2* value,of the lesions. We compared these metrics across groups and performed multiple Lo-gistic regression analyses to identify risk factors associated with LVI and LNM. Additionally,we calculated the area under the curve (AUC) of the receiver operating characteristic (ROC) to evaluate predictive efficacy. Smooth curve fitting and Spearman correlation analysis were used to evaluate the relationship between imaging and blood cell parameters. Results:The R2* value,neutrophil to lymphocyte ratio (NLR),sys-temic immune-inflammation index (SII),and systemic inflammatory response index (SIRI) were significantly higher in the LVI-positive group compared to those in the negative group. Similarly,the LNM-positive group showed higher R2* value,FF value,NLR,platelet to lymphocyte ratio (PLR),SII,and SIRI than the negative group,with all differences being statistically significant (P<0.05). R2* and SII were identified as in-dependent risk factors for LVI,with AUCs of R2*,SII,and R2*+SII being 0.752,0.802,and 0.883,respectively. R2*,FF,and SII were independ-ent risk factors for LNM,and the AUCs of R2*,FF,SII,R2*+FF,and R2*+FF+SII were 0.733,0.702,0.778,0.825 and 0.857,respectively. Cor-relation analysis indicated a positive relationship between FF and several blood cell parameters,including NLR,monocyte to lymphocyte ra-tio (MLR),SII,and SIRI (r=0.534,0.451,0.353,0.468,P<0.05). Conclusions:Both mDixon-Quant imaging and blood cell parameters are effect-ive for assessing LVI and LNM status in RC. In addition,the correlation between FF and various blood cell parameters highlights the potential role of abnormal lipid metabolism and inflammatory responses in the development of RC,suggesting new avenues for developing clinically tailored treatment protocols.

Objective:To investigate the value of mDixon-Quant imaging combined with blood cell parameters in assessing lymphovascular invasion (LVI) and lymph node metastasis (LNM) in rectal cancer (RC). Methods:Clinical and magnetic resonance imaging (MRI) data were retrospectively collected from 62 patients with pathologically confirmed RC at North China University of Science and Technology Affiliated Hospital from November 2022 to June 2024. We calculated the ratio of blood cell parameters and measured the mDixon-Quant parameters,including fat fraction (FF),R2* value,and T2* value,of the lesions. We compared these metrics across groups and performed multiple Lo-gistic regression analyses to identify risk factors associated with LVI and LNM. Additionally,we calculated the area under the curve (AUC) of the receiver operating characteristic (ROC) to evaluate predictive efficacy. Smooth curve fitting and Spearman correlation analysis were used to evaluate the relationship between imaging and blood cell parameters. Results:The R2* value,neutrophil to lymphocyte ratio (NLR),sys-temic immune-inflammation index (SII),and systemic inflammatory response index (SIRI) were significantly higher in the LVI-positive group compared to those in the negative group. Similarly,the LNM-positive group showed higher R2* value,FF value,NLR,platelet to lymphocyte ratio (PLR),SII,and SIRI than the negative group,with all differences being statistically significant (P<0.05). R2* and SII were identified as in-dependent risk factors for LVI,with AUCs of R2*,SII,and R2*+SII being 0.752,0.802,and 0.883,respectively. R2*,FF,and SII were independ-ent risk factors for LNM,and the AUCs of R2*,FF,SII,R2*+FF,and R2*+FF+SII were 0.733,0.702,0.778,0.825 and 0.857,respectively. Cor-relation analysis indicated a positive relationship between FF and several blood cell parameters,including NLR,monocyte to lymphocyte ra-tio (MLR),SII,and SIRI (r=0.534,0.451,0.353,0.468,P<0.05). Conclusions:Both mDixon-Quant imaging and blood cell parameters are effect-ive for assessing LVI and LNM status in RC. In addition,the correlation between FF and various blood cell parameters highlights the potential role of abnormal lipid metabolism and inflammatory responses in the development of RC,suggesting new avenues for developing clinically tailored treatment protocols.

As a branched chain amino acid, L-valine is widely used in the medicine and feed sectors. In this study, a microbial cell factory for efficient production of L-valine was constructed by combining various metabolic engineering strategies. First, precursor supply for L-valine biosynthesis was enhanced by strengthening the glycolysis pathway and weakening the metabolic pathway of by-products. Subsequently, the key enzyme in the L-valine synthesis pathway, acetylhydroxylate synthase, was engineered by site-directed mutation to relieve the feedback inhibition of the engineered strain. Moreover, promoter engineering was used to optimize the gene expression level of key enzymes in L-valine biosynthetic pathway. Furthermore, cofactor engineering was adopted to change the cofactor preference of acetohydroxyacid isomeroreductase and branched-chain amino acid aminotransferase from NADPH to NADH. The engineered strain C. glutamicum K020 showed a significant increase in L-valine titer, yield and productivity in 5 L fed-batch bioreactor, up to 110 g/L, 0.51 g/g and 2.29 g/(L‧h), respectively.
Valine ; Corynebacterium glutamicum/genetics* ; Metabolic Engineering ; Amino Acids, Branched-Chain ; Bioreactors

Objective: Traditional uterine manipulator is considered as the main reason for short survival of patients with early-stage cervical cancer during minimally invasive surgery. This study aims to assess the sealing effect of magnetic-sealing uterine manipulators (MUMs) in isolated uteruses. Methods: The study was performed on isolated uterus from patients with early-stage cervical cancer who underwent open abdominal radical hysterectomy between November 2019 to April 2021. Right-angle forceps closure tests (groups 1 and 3) were defined as control tests. One experimental MUM closure test (group 2) and 2 control tests were respectively carried out in each of the isolated uterus. DNA ploidy analysis system was used to observe exfoliated cells. Statistical analysis was performed using Wilcoxon signed-rank test to assess the sealing effect of MUM. Results: We identified 36 patients. No regional node metastasis was discovered and only one tumor was larger than 4.0 cm in diameter. The mean of exfoliated tumor cells in groups 1, 2, and 3 were 1, 1, and 2, respectively. There was no significant difference in the quantity of exfoliated cells between groups 1 and 3 (p=0.476), so the results of the 2 groups were merged. Subsequently, a significant difference was observed between combined right-angle forceps closure tests and MUM closure tests (p=0.022). Conclusion The sealing effect of MUM was better than that of right-angle forceps. MUM can effectively seal cervical cancer cells in the cup cover, avoiding the dissemination of tumor cells.

Background::Non-smokers account for a large proportion of lung cancer patients, especially in Asia, but the attention paid to them is limited compared with smokers. In non-smokers, males display a risk for lung cancer incidence distinct from the females—even after excluding the influence of smoking; but the knowledge regarding the factors causing the difference is sparse. Based on a large multicenter prospective cancer screening cohort in China, we aimed to elucidate the interpretable sex differences caused by known factors and provide clues for primary and secondary prevention.Methods::Risk factors including demographic characteristics, lifestyle factors, family history of cancer, and baseline comorbidity were obtained from 796,283 Chinese non-smoking participants by the baseline risk assessment completed in 2013 to 2018. Cox regression analysis was performed to assess the sex difference in the risk of lung cancer, and the hazard ratios (HRs) that were adjusted for different known factors were calculated and compared to determine the proportion of excess risk and to explain the existing risk factors.Results::With a median follow-up of 4.80 years, 3351 subjects who were diagnosed with lung cancer were selected in the analysis. The lung cancer risk of males was significantly higher than that of females; the HRs in all male non-smokers were 1.29 (95% confidence interval [CI]: 1.20-1.38) after adjusting for the age and 1.38 (95% CI: 1.28-1.50) after adjusting for all factors, which suggested that known factors could not explain the sex difference in the risk of lung cancer in non-smokers. Known factors were 7% (|1.29-1.38|/1.29) more harmful in women than in men. For adenocarcinoma, women showed excess risk higher than men, contrary to squamous cell carcinoma; after adjusting for all factors, 47% ([1.30-1.16]/[1.30-1]) and 4% ([7.02-6.75]/[7.02-1])) of the excess risk was explainable in adenocarcinoma and squamous cell carcinoma. The main causes of gender differences in lung cancer risk were lifestyle factors, baseline comorbidity, and family history.Conclusions::Significant gender differences in the risk of lung cancer were discovered in China non-smokers. Existing risk factors did not explain the excess lung cancer risk of all non-smoking men, and the internal causes for the excess risk still need to be explored; most known risk factors were more harmful to non-smoking women; further exploring the causes of the sex difference would help to improve the prevention and screening programs and protect the non-smoking males from lung cancers.

Objective: To identify epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma based on 18 F-fluorodeoxyglucose (FDG) PET/CT radiomics and clinical features and to distinguish EGFR exon 19 deletion (19 del) and exon 21 L858R missense (21 L858R) mutations using FDG PET/CT radiomics. Materials and Methods: We retrospectively analyzed 179 patients with lung adenocarcinoma. They were randomly assigned to training (n = 125) and testing (n = 54) cohorts in a 7:3 ratio. A total of 2632 radiomics features were extracted from the tumor region of interest from the PET (1316) and CT (1316) images. Six PET/CT radiomics features that remained after the feature selection step were used to calculate the radiomics model score (rad-score). Subsequently, a combined clinical and radiomics model was constructed based on sex, smoking history, tumor diameter, and rad-score. The performance of the combined model in identifying EGFR mutations was assessed using a receiver operating characteristic (ROC) curve. Furthermore, in a subsample of 99 patients, a PET/CT radiomics model for distinguishing 19 del and 21 L858R EGFR mutational subtypes was established, and its performance was evaluated. Results: The area under the ROC curve (AUROC) and accuracy of the combined clinical and PET/CT radiomics models were 0.882 and 81.6%, respectively, in the training cohort and 0.837 and 74.1%, respectively, in the testing cohort. The AUROC and accuracy of the radiomics model for distinguishing between 19 del and 21 L858R EGFR mutational subtypes were 0.708 and 66.7%, respectively, in the training cohort and 0.652 and 56.7%, respectively, in the testing cohort. Conclusion The combined clinical and PET/CT radiomics model could identify the EGFR mutational status in lung adenocarcinoma with moderate accuracy. However, distinguishing between EGFR 19 del and 21 L858R mutational subtypes was more challenging using PET/CT radiomics.