OBJECTIVE: To analyze the clinical characteristics of patients with 11q23 rearrangement acute lymphoblastic leukemia (ALL) with non-KMT2A::AFF1 fusion genes. METHODS: The clinical data of 10 patients with KMT2A fusion gene positive and partner gene non-AFF1 ALL admitted to Henan Cancer Hospital from December 2016 to December 2024 were retrospectively summarized. The immunophenotype, molecular genetic characteristics, clinical manifestations and disease prognosis of these patients were analyzed. This research has been approved by the Medical Ethics Committee of Henan Cancer Hospital (Ethics No.: 2019342). RESULTS: Among the 10 patients, the fusion genes were KMT2A::MLLT1 in 7 cases, KMT2A::MLLT4, KMT2A::MLLT3 and KMT2A::MLLT10 in 1 case each. The European Group for the Immunological Classification of Leukemias (EGIL) classification included 6 cases of T-ALL, 2 cases of pro-B-ALL, 1 case of Common-B-ALL and 1 case of pre-B-ALL. 4 cases of B-ALL all expressed CD19, cCD79a, CD38 and HLA-DR, and some expressed CD34 and CD22, without expression or weak expression of CD10, without expression of CD20. One case was accompanied by myeloid marker CD15 expression. 6 cases of T-ALL all expressed CD34, CD7, most expressed CD38, and some expressed CD3, CD5, CD2, CD4 and CD8, and 1 case expressed CD4 and CD8 together. Chromosomal abnormalities were detected in 3 cases, 5 cases were positive for WT1 fusion gene, and 6 cases had gene alterations. 9 patients achieved the first complete remission (CR1) during chemotherapy, and 1 patient relapsed within 6 months after CR1. At the last follow up, 1 patient (the fusion gene was KMT2A::MLLT4) remained unrelieved. There were 2 cases of KMT2A rearrangement (KMT2A-r) persistent positive (+/+) and 8 cases of KMT2A-r negative (+/-). The overall survival (OS) rate and leukemia-free survival (LFS) rate of patients with KMT2A-r persistent positive were significantly lower than those of patients with negative change, and the differences were statistically significant (P values were all < 0.05). Among the 3 patients who received chemotherapy+allogeneic hematopoietic stem cell transplantation (allo-HSCT), no relapse was observed until the follow up day. The OS rate and LFS rate of patients with KMT2A::MLLT1 and chemotherapy+allo-HSCT were higher than those of non-KMT2A::MLLT1 and single chemotherapy patients, and the differences were not statistically significant (P values were all ≥ 0.05). There was no significant difference in OS rate and LFS rate between T-ALL and B-ALL patients (P values were all ≥ 0.05). The median LFS time of the 10 patients was 32 (0 ~ 100) months, and the median OS time was 36 (1 ~ 101) months. CONCLUSION The 11q23 rearrangement ALL with non-KMT2A::AFF1 transcript is mainly KMT2A::MLLT1, T-ALL is more common, and the rate of chromosomal karyotype detection is relatively low. Persistent positive KMT2A-r is unfavorable for patient survival, and allo-HSCT during the CR1 period may improve patient survival.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Female ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Adult ; Adolescent ; Chromosomes, Human, Pair 11/genetics* ; Child ; Transcriptional Elongation Factors/genetics* ; Gene Rearrangement ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies ; Young Adult ; Middle Aged ; Prognosis ; Child, Preschool ; DNA-Binding Proteins/genetics*

ObjectiveTo compare the differences in color， odor， coumarin content and microbial community composition of Angelicae Dahuricae Radix（ADR） during different drying processes， and to explore the correlation between changes in microbial community composition and changes in quality indexes of ADR. MethodsThe fresh ADR was processed at three drying temperatures（50， 70， 100 ℃） by drying and steaming cutting， semi-fresh cutting and drying， fresh cutting and drying， and sulfur fumigation methods. The color values of samples were extracted by Adobe Photoshop 2022 software and subjected to principal component analysis（PCA）， electronic nose was used to identify the odor information of medicinal powders and subjected to loadings analysis， PCA， and linear discriminant analysis（LDA）， and high performance liquid chromatography（HPLC） was used to determine the contents of five coumarins（bergapten， oxypeucedanin， imperatorin， phellopterin， isoimperatorin）. The samples for microbial detection were taken from fresh dried samples， 50 ℃（dried and steamed cut， sulfur fumigated） samples， and 100 ℃（dried and steamed cut） samples when the water content was 50% and 14%， respectively. And the changes of microbial community composition during processing were determined by high-throughput sequencing method. The relationship between the changes of microbial community composition and the changes of odor， color and active component content of ADR during drying process was analyzed by Pearson correlation analysis. ResultsThe color quantification results showed that an increase in drying temperature led to the decrease of brightness value（L）， and the increases of red-green value（a） and yellow-blue value（b）， and the change of processing method had no obvious effect on the color of medicinal materials. The results of odor quantification showed that W1S， W2S， W5S， W2W and W1W sensor were sensitive to the odor changes of ADR and could be used to distinguish ADR decoction pieces from different processing methods. The results of HPLC showed that the coumarin content of ADR decreased with the increase of drying temperature and the delay of processing time， the optimal processing method was drying and steaming cutting method， and the optimal temperature was 50 ℃. High-throughput sequencing results showed that the dominant bacteria in ADR during processing were Achromobacter， Agrobacterium， Nocardioides， Mycobacterium and Enterobacter， the dominant fungi were Coprinopsis， Meyerozyma and Apiotrichum. The results of correlation analysis showed that the quality indexes of ADR were positively correlated with Agrobacterium， Mycobacterium in bacteria， Candida in fungi， and negatively correlated with Bacillus in bacteria. ConclusionThere are significant differences in the color， odor， coumarin content and microbial community composition of ADR in different drying processes， and the best drying method is drying and steaming cutting at 50 ℃. The relative abundance changes of 9 bacterial genera and 4 fungal genera are closely related to the quality formation of ADR during the drying process.

Objective To explore the changes in serum epidermal growth factor receptor(EGFR)and cancer anti-gen 125(CA125)levels in pregnant women with adenomyosis(AM)and their relationship with pregnancy outcomes.Methods A total of 108 pregnant women with AM(AM pregnant women group)admitted to Baoding Maternal And Child Health Hospital from June 2021 to August 2023 were collected and divided into a good preg-nancy group(n=43)and a poor pregnancy group(n=65)based on pregnancy outcomes.Meanwhile,AM patients were selected as AM group and 108 pregnant women with normal pregnancy test were selected as control group.ELISA was applied to detect the serum level of EGFR and CA125.Pearson correlation was applied to analyze the correlation between serum EGFR and CA125 in AM pregnant women.Multivariate logistic regression was applied to analyze the factors that affected the outcome of AM pregnancy.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum EGFR and CA125 levels for AM pregnancy outcomes.Results Compared with the control group,serum level of EGFR and CA125 in AM group and AM pregnant women group were significantly increased and serum level of EGFR and CA125 in AM pregnant women group was higher than that in AM group(P＜0.05).As the depth grading of endometrial invasion increased,serum level of EGFR and CA125 increased sequentially;The serum level of EGFR and CA125 was obviously elevated in diffuse type and proliferate phase(P＜0.05).The expression level of EGFR and CA125 in the serum of AM pregnant women with premature rupture of membranes,premature birth,placenta previa,and miscarriage was significantly increased(P＜0.05).According to Pearson correlation analysis,there was a positive correlation between serum EGFR and CA125 in AM pregnant women(r=0.487,P＜0.05).The serum level of EGFR and CA125 in good pregnancy group was lower than that in poor pregnancy group(P＜0.05).The area under the curve(AUC)of serum EGFR,CA125,and their combined prediction for AM pregnancy outcome was 0.880,0.835,and 0.955,re-spectively and the combined prediction of AUC for AM pregnancy outcome was significantly higher than that of se-rum EGFR and CA125 alone prediction(Zcombination-EGFR=2.279,Zcombination-CA125=3.304,both P＜0.05).Conclusions Serum level of EGFR and CA125 in AM pregnant women is elevated,which is closely related to pregnancy outcomes and is potential risk factor for poor pregnancy in AM.The combination of the two is more ef-fective in predicting pregnancy outcomes in AM.

This study aims to research the relationship between arterial stiffness and serum indirect bilirub in levels(IBIL)in patients with type 2 diabetes by measuring brachial-ankle pulse wave velocity (baPWV). The clinical data of 1 327 patients with T2DM admitted to Qingdao Huangdao District People′s Hospital from July 1st, 2018 to March 1st, 2024 were retrospectively and cross-sectionally analyzed (609 men and 718 women; age range, 45.3-79.5 years; median age, 60.3 years; mean age, 61.4 years). The subjects were stratified based on gender-specific quartiles of IBIL values(male, Q1:<6.7 μmol/L, Q2:6.7-8.9 μmol/L, Q3:8.9-12.3 μmol/L, Q4:≥12.3 μmol/L;female, Q1:<6.4 μmol/L, Q2:6.4-7.9 μmol/L, Q3:7.9-10.4 μmol/L, Q4:≥10.4 μmol/L), and a high baPWV was defined as greater than 18.37 m/s (75th percentile). The results showed that the serum IBIL concentration was negatively correlated with the duration of diabetes ( r=-0.142, P=0.010), the SBP ( r=-0.158, P=0.005) and the baPWV ( r=-0.194, P<0.001) in women and was positively correlated with TC (men: r=0.282, P<0.001; women: r=0.237, P<0.001), HDL-C (men: r=0.171, P=0.011; women: r=0.287, P<0.001) and LDL-C (men: r=0.196, P=0.009; women: r=0.233, P<0.001) levels in both genders. Dividing IBIL levels into quartiles, there were significant statistical differences in the incidence of high baPWV among different subgroups of female patients ( χ 2=36.468, P<0.001), and the incidence of high baPWV showed a decreasing trend with increasing IBIL levels. After adjusting for confounding factors, the IB levels were inversely associated with a greater risk of a high baPWV both as a continuous variable [a 1-SD difference; odds ratio ( OR):0.836; 95% confidence interval ( CI):0.774-0.942; P=0.009] and when categorized in quartiles (the highest vs. the lowest quartile; OR:0.381; 95% CI:0.162-0.897; P=0.025) in women but not in men. Low IBIL levels were significantly associated with arterial stiffness in middle-aged and elderly women with type 2 diabetes. In conclusion, the serum IBIL levels were independent protective factors for macrovascular disease in middle-aged and elderly diabetic women.

Objective:To examine the relationships between perceived organizational support in job resources, self-efficacy in personal resources, and teaching commitment based on the job requirement-resource model, and to explore the path of influencing clinical teachers' teaching commitment.Methods:Using the convenience sampling method, 463 clinical teachers from 16 university-affilicated hospitals in Shandong Province, China were selected as the study subjects. Surveys were conducted using the Perceived Organizational Support Scale, Self-efficacy Scale, and Teaching Commitment Scale. A statistical analysis was performed using SPSS 26.0. A structural equation model was constructed using AMOS 26.0 to test the mediation effect.Results:①The level of teaching commitment of clinical teachers was relatively high, with a total score of (45.25±9.21) points. The total score of perceived organizational support was (38.22±9.75) points, and the total score of self-efficacy was (112.27±17.30) points. ②Perceived organizational support and self-efficacy were positively correlated with teaching commitment ( r=0.59, r=0.65, both P<0.01). ③ Perceived organizational support had significant and direct positive effects on teaching commitment and self-efficacy ( β=0.36, β=0.51, both P<0.01). Self-efficacy significantly and positively affected teaching commitment ( β=0.47, P<0.01). Self-efficacy played a significant and partial mediating role in the effect of perceived organizational support on teaching commitment (standardized mediating effect value of 0.239, P<0.01), and the mediating effect percentage was 39.83%. Conclusions:Perceived organizational support not only directly predicts clinical teachers' teaching commitment, but also indirectly affects teaching commitment through self-efficacy. University-affiliated hospital administrators should pay attention to clinical teachers' perceived organizational support to improve their self-efficacy and teaching commitment, thereby ensuring teaching quality.

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Objective To observe the value of CT radiomics machine learning(ML)model for predicting stone free rate(SFR)of urinary calculi after retrograde intrarenal surgery(RIRS).Methods Totally 216 patients with urinary calculi who underwent RIRS were retrospectively enrolled and divided into residual group(n=73)and non-residual group(n=143).Univariate and multivariate logistic regression(LR)were performed to analyze clinical data and CT manifestations of stones to screen independent predictors of SFR after RIRS.Window width and window level normalization combined with max-min normalization(denoted as method a),max-min normalization(denoted as method b),window width and window level normalization(denoted as method c)and non-normalization(denoted as method d)of pre-RIRS abdominal CT were performed,respectively,and the best radiomics features of stones were extracted and screened to establish ML models,including support vector machine(SVM),LR and stochastic gradient descent(SGD)models,and the best ML model was screened.RUSS and modified S.T.O.N.E scores were evaluated based on pre-RIRS CT for predicting SFR of urinary calculi after RIRS.A combined model was then constructed with the independent predictors and the best ML model.The predictive efficacy of each model and scoring system were assessed.Results The number of stones,CT value and volume of the maximum stone were all independent predictors of SFR after RIRS(all P＜0.05).The area under the curve(AUC)of SVM model constructed with images preprocessed by method b was the highest(0.861),higher than that of the total scores of RUSS and modified S.T.O.N.E(AUC=0.750,0.759,both P＜0.05)but not different from that of combined model(AUC=0.853,P=0.775).Conclusion Radiomics SVM model based on max-min normalization preprocessed CT could effectively predict SFR of urinary calculi after RIRS.

ObjectiveTo establish the fingerprints of 15 batches of Hengzhi Kechuan capsules， to quantitatively analyze 10 index components， and to evaluate the quality uniformity of samples from different batches. MethodsThe fingerprints and quantitative analysis of Hengzhi Kechuan capsules were established by a combination method of high performance liquid chromatography coupled with diode array detector and charged aerosol detector（HPLC-DAD-CAD）， adenosine， guanosine， vanillic acid， safflomin A， agarotetrol， naringin， hesperidin， militarine， ginsenoside Rb₁， and glycyrrhizic acid were selected as quality attribute indexes. A total of 15 batches of Hengzhi Kechuan capsules from 2022 to 2024（3 boxes per batch） were qualitatively and quantitatively analyzed， and the quality uniformity level of the manufacturers was characterized by parameters of intra-batch consistency（P_A） and inter-batch consistency（P_B）. The homogeneity and difference of quality attribute indexes of samples from different years were analyzed by heatmap clustering analysis. ResultsHPLC fingerprints and quantitative method of Hengzhi Kechuan capsules were established， and the methods could be used for qualitative and quantitative analysis of this preparation， which was found to be stable and reliable by method validation. The similarity of fingerprints of 15 batches of samples was 0.887-0.975， a total of 13 common peaks were calibrated， and 10 common peaks were designated， all of which were quality attribute index components. The results of quantitative analysis showed that the contents of the above 10 ingredients in the samples were 0.038-0.078， 0.115-0.251， 0.007-0.018， 0.291-0.673， 0.122-0.257， 0.887-1.905， 1.841-3.364， 1.412-2.450， 2.207-3.112， 0.650-1.161， respectively. And the contents of ginsenoside Rb₁ and glycyrrhizic acid met the limit requirements in the 2020 edition of Chinese Pharmacopoeia. For the samples from 15 batches， the P_A values of the 10 index components were all <10%， indicating good intra-batch homogeneity， and the P_B values ranged from 33.86% to 92.97%， suggesting that the inter-batch homogeneity was poor. Heatmap clustering analysis showed that the samples from different years were clustered into separate categories， and adenosine， guanosine， safflomin A， naringin， hesperidin and agarotetrol were the main differential components. ConclusionThe intra-annual quality uniformity of Hengzhi Kechuan capsules is good and the inter-annual quality uniformity is insufficient， which may be related to the quality difference of Pinellinae Rhizoma Praeparatum， Carthami Flos， Citri Sarcodactylis Fructus， Citri Reticulatae Pericarpium， Aquilariae Lignum Resinatum， Citri Fructus， etc. In this study， the fingerprint and multi-indicator determination method of Hengzhi Kechuan capsules was established， which can be used for more accurate and efficient quality control and standardization enhancement.

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

ObjectiveTo explore quality difference factors of Perillae Caulis based on the contents of multiple chemical components and comprehensively evaluate the quality. MethodsA total of 32 batches of Perillae Caulis samples were collected from 12 producing areas such as Hebei， Anhui and Guangdong， and their diameter range， epidermis color and producing areas were recorded. Total flavonoids， total phenols， volatile oils， 5 active components and 84 volatile components in 32 batches of samples were quantitatively or semi-quantitatively determined by colorimetry， ultra performance liquid chromatography-photodiode array detector（UPLC-PDA） and gas chromatography-mass spectrometry（GC-MS）. Then the differences between the contents of these components were analyzed by principal component analysis（PCA） and non-parametric test. According to the weights of the index components determined by PCA model， entropy weight-technique for order preference by similarity to ideal solution（TOPSIS） model was constructed to evaluate the quality of Perillae Caulis with different characters and origins. ResultsThere were significant differences in the composition of Perillae Caulis with different diameters， epidermis colors and producing areas， and 9 differential components were screened out， including 6 index constituents（total flavonoids， total phenols， caffeic acid， scutellarin， rosmarinic acid and luteolin） and 3 volatile components（caryophyllene oxide， （-）-humulene epoxide Ⅱ， 14-hydroxycaryophyllene）， of which 6 index constituents were higher in samples with small diameter， purple-brown epidermis and southern origin， while the contents of 3 volatile components were higher in samples with large diameter， dark-brown epidermis and northern origin. A significant difference was shown in the model scores of different diameters， epidermis colors and origins（P<0.05）， and the scores of Perillae Caulis with small diameter and purple-brown epidermis from southern area， especially Guangdong， had a high score. ConclusionThere are significant differences in the composition and content of chemical constituents between different diameters， epidermal colors and production areas of Perillae Caulis， samples showing small diameter， owing purple-brown epidermis， and originating from Guangdong were of higher-quality due to their higher content of 8 key indices.