Objective:To evaluate the diagnostic value of non-targeted detection of metabolic fingerprinting in pulmonary nodules and to analyze the clinical effective model of multi-omics for assessing the malignant risk of pulmonary nodules.Methods:A total of 73 patients who underwent chest CT and completed pathological diagnosis and non-targeted detection of metabolic fingerprinting at Shandong Provincial Hospital Affiliated to Shandong First Medical University from November 2021 to October 2024 were selected as the research subjects. According to the postoperative histopathological diagnosis, the patients were divided into the lung malignant nodule group (61 cases) and the lung benign nodule group (12 cases). General clinical data of the patients, including sex, age, smoking history, and family history of tumors, as well as imaging data, including nodule density, nodule size, nodule location, nodule number, and special imaging manifestations (spiculation, lobulation, vacuole sign, vascular convergence sign, etc.), and non-targeted detection of metabolic fingerprinting results were collected. The above data were compared between the two groups of patients, and the receiver operator characteristic (ROC) curve was drawn to evaluate the predictive value of each model. Results:There were statistically significant differences in age ( t=4.41, P<0.001), nodule size ( Z=2.67, P=0.008), nodule density ( χ2=4.64, P=0.031), and spiculation ( χ2=7.67, P=0.006) between the lung malignant nodule group and the lung benign nodule group. There were no statistically significant differences in sex, smoking history, family history of lung cancer, nodule number, nodule location, lobulation, vacuole sign, vascular convergence sign, pleural indentation sign, calcification sign, bronchial truncation sign, vascular supply sign, and bronchial air sign (all P>0.05). The number of non-targeted detection of metabolic fingerprinting high-risk patients in the lung malignant nodule group (36 cases) was significantly higher than that in the lung benign nodule group (0 case) ( χ2=13.97, P<0.001). ROC curve analysis showed that the area under the curve of the Brock model combined with non-targeted detection of metabolic fingerprinting was 0.930 (95% CI: 0.872-0.988), which was greater than that of the Brock model (0.856, 95% CI: 0.769-0.942, Z=0.27, P=0.040) and non-targeted detection of metabolic fingerprinting (0.768, 95% CI: 0.650-0.887, Z=0.30, P=0.004) alone. Conclusions:Non-targeted detection of metabolic fingerprinting risk assessment may serve as a non-invasive method to assist the Brock model in the diagnosis of pulmonary nodules and has good application value. The combination of the Brock model and non-targeted detection of metabolic fingerprinting can more accurately distinguish the benign and malignant nature of pulmonary nodules.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

Objective:To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL).Methods:This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children′s Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors.Results:Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×10 9/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively ( χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant ( χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively ( χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%, χ2=4.13, P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%, χ2=4.06, P=0.044;(58.3±18.6)% vs. (85.7±3.2)%, χ2=9.44, P=0.002). Multivariate analysis showed that age ( OR=0.58, 95% CI 0.35-0.97) and white blood cell count at first diagnosis ( OR=0.43, 95% CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 ( OR=0.55,95% CI 0.31-0.97), ETV6-RUNX1 fusion gene ( OR=0.13,95% CI 0.03-0.54), MLL gene rearrangement ( OR=2.55,95% CI 1.18-5.53) and white blood cell count at initial diagnosis ( OR=0.52,95% CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions:The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

Objective:To explore whether the deubiquitinating enzyme deubiquitin ligase 9X(USP9X)affects the proliferation of nasopharyngeal carcinoma(NPC)cells via regulating forkhead box Ml(FOXM1)mediated glycolysis. Methods:Western blotting and real-time fluorescence quantitative PCR,respectively,were used to detect the protein and mRNA expression levels of USP9X in NPC tissue and normal nasal mucosa tissue.NPC cells(CNE2 and HNE2)were infected with lentivirus carrying specific shRNA targeting USP9X gene(shUSP9X)or full-length USP9X gene(Flag-USP9X)for USP9X overexpression.CCK-8 assay was used to evaluate the effect of USP9X silencing or overexpression on the proliferation of NPC cells.Cellular energy metabolism assay and extracellular acidification rate(ECAR)assay were performed to investigate the impact of USP9X alteration on the glycolysis of NPC cells.The interaction between USP9X and FOXM1 was analyzed using ubibrowser_v3/database,co-immunoprecipitation,and ZDOCK software,and the changes in FOXM1 protein ubiquitination levels upon USP9X silencing was examined.Real-time fluorescence quantitative PCR and Western blotting,respectively,were used to detect the effect of USP9X alteration on the expression of FOXM1 mRNA and protein in NPC cells.Finally,FOXM1 expression was restored in USP9X silencing CNE2 cells by expression of recombinant plasmid Flag-FOXM1 carrying full-length FOXM1 gene through lentiviral infection.CCK-8 assay was used to evaluate the effect of FOXM1 upregulation on the proliferation of CNE2 cells.Cellular energy metabolism assay and ECAR assay were used to investigate the effect of FOXM1 upregulation on the glycolysis of CNE2 cells. Results:Compared with normal nasal mucosa tissue,the expression levels of USP9X mRNA and protein were significantly increased in NPC tissues(P＜0.05).After USP9X downregulation,the proliferation and glycolysis of CNE2 cells was significantly inhibited as indicated by the results of CCK-8 assay,cellular energy metabolism assay and ECAR assay(P＜0.05).In contrast,the proliferation and glycolysis of HNE2 cells was significantly enhanced after USP9X upregulation(P＜0.05).The interaction between USP9X and FOXM1 was confirmed by ubibrowser_v3/database,co-immunoprecipitation,and ZDOCK software analysis.Silencing USP9X could significantly increase FOXM1 ubiquitination in CNE2 cells.Overexpressing FOXM1 in low-USP9X CNE2 cells restored the proliferation and glycolysis activity of NPC cells(P＜0.05). Conclusion:USP9X can enhance NPC cell glycolysis by inhibiting FOXM1 ubiquitination and subsequent degradation,thereby promoting NCP cell proliferation.USP9X may be a potential novel therapeutic target for the treatment of NPC.

Objective To investigate the effects of NVP-BEZ235 on proliferation and apoptosis of human cholangiocarcinoma(CCA) cell QBC939 in vitro and to reveal the antineoplastic mechanisms of NVP-BEZ235.Methods Human CCA cell line QBC939 was used in this study.Cell apoptosis by NVP-BEZ235 was analyzed using the flow cytometry.Cell growth inhibition by NVP-BEZ235 for 24h 48h 72h by MTT assay.The antineoplastic mechanisms of NVP-BEZ235 for 48h were assessed by western blotting for PARP、Bcl-2、Akt、p-Akt、c-FLIPL and Mcl-1 assay in QBC939 cell.Results NVP-BEZ235 treatment inhibited the proliferation and induced apoptosis of human CCA cell QBC939,which appeared time-dependent and concentration-dependent effects.NVP-BEZ235 reduced protein levels of Mcl-1、c-FLIPL and Bcl-2 and downregulate protein level of p-Akt significantly.Conclusion NVP-BEZ235 inhibited the phosphorylation of Akt.NVP-BEZ235 downregulated Bcl-2、c-FLIPL、Mcl-1 protein level via PI3K/AKT signaling pathway to induce apoptosis and inhibit the proliferation of human CCA cell QBC939.

Allergic rhinitis (AR) is a noninfectious inflammatory response in nasal mucosa caused by allergens, which is contacted by a specific individual. The immune imbalance of Th1/Th2 plays an important role in the pathogenesis of AR. In?terleukin (IL)-33, the novel cytokine of IL-1 family, is an important regulatory factor of allergic diseases, autoimmune diseas?es and various inflammatory diseases. IL-33 is a kind of alarm, which is mainly secreted and released by damaged tissues and cells, especially impaired epithelial cells and endothelial cells. IL-33 binding to its receptor ST2L can activate a variety of immune cells to produce Th2 cytokines, precipitating and maintaining Th2 polarization, increasing AR immune inflamma?tion, which is the new target of AR in research and treatment. In this article, we have done a brief overview for the biological functions of IL-33 and its receptor ST2L and the research progress in the AR.

OBJECTIVE: To study the expression of IL-33 and its receptor ST2 in the nasal mucosa of allergic rhinitis (AR) patients, and to explore the role of IL-33 and ST2 in the pathogenesis of AR. METHOD: Collected 24 cases of nasal septum deviation of patients with AR as AR group,and selected 20 patients with simple septum deviation as normal control. In addition, collected 20 cases diagnosed with AR, who accepted standardized specific immunotherapy(SIT). RESULT: Immunohistochemical results found more positively stained cells of IL-33 and ST2 in AR patients than normal control group, the difference was statistically significant (P < 0.05), Western-Blot detected that IL-33 and ST2 protein level were significantly higher in AR than the normal control group (P < 0.01), PCR detected that the expression of IL-33mRNA and ST2mRNA were increased in AR group compared with the control group, the difference was statistically significant (P < 0.05). While, the serum IL-33 levels in AR were decreased before treatment (72.37 ± 16.18) ng/L than after six months of SIT (47.35 ± 10.59) ng/L,and the difference was statistically significant (P < 0.05). CONCLUSION IL-33 and its receptor ST2 were highly expressed in the nasal mucosa of patients with AR, suggesting that IL-33/ST2 may play an important role in the pathogenesis of allergic rhinitis. Serum levels of IL-33 were significantly decreased after SIT treatment, suggesting that IL-33 may have a positive correlation with the severity of AR.
Case-Control Studies ; Humans ; Immunotherapy ; Interleukin-33 ; metabolism ; Nasal Mucosa ; metabolism ; Nasal Septum ; abnormalities ; Receptors, Interleukin ; metabolism ; Rhinitis, Allergic ; drug therapy ; metabolism ; pathology

Objective The purpose of this study was to investigate the efficacy and safety of bortezomib +doxorubicin + dexamethasone (PAD) regimen in the treatment of patients with multiple myeloma (MM) . Methods Thirty-eight patients with MM in our hospital were selected and randomly divided into observation group and control group with 19 cases in each. The observation group was treated with PAD regimen and the control group was treated with VAD regimen (vincristine+doxorubicin+dexamethasone) . Clinical efficacy and adverse reaction were compared between the two groups. Results The effective rate and total effective rate of the observation group were 52.63%and 78.95%respectively, which were significantly higher than those of the control group ( <0.05 and <0.05) . There was no statistical difference in the incidence of adverse events between the two groups ( >0.05) . Conclusion PAD regimen could improve the clinical effect of treating patients with MM, and the adverse reactions can be tolerated. It is safe and worthy of clinical application.

OBJECTIVE: To explore the expression of IL-35, Epstein-Barr virus-induced gene 3 (EBI3) mRNA and IL-12A mRNA in peripheral blood of patients with allergic rhinitis and its significance. METHOD: Peripheral blood were collected from patients with allergic rhinitis (46 cases) and healthy human controls(30 cases). The level of IL-35 in serum was measured by enzyme-linked immunosorbent assay. The subunit EB13 and IL-12A of IL-35 mRNA expressions in peripheral blood mononuclear cell(PBMC) were detected by SYBR Green real-time quantitative PCR. RESULT: IL-35 level in AR group (251.22 +/- 46.27) ng/L was significantly lower compared with that in the normal control group (382.17 +/- 25.41) ng/L, (P < 0.01). The mRNA expression level of EBI3 in the patients with allergic rhinitis was significantly lower than that in the normal control group (P < 0.01), AR group EB13 mRNA level was about half of that in the normal control group. But the mRNA expression level of IL-12A in the patients with allergic rhinitis has not significant difference with that in the normal control group (P > 0. 05). CONCLUSION The decrease of IL-35 and EBI3 mRNA in AR,indicated that IL-35 and EBl3 mRNA may play an important role in allergic rhinitis.
Adolescent ; Adult ; Case-Control Studies ; Child ; Female ; Humans ; Interleukin-12 Subunit p35 ; blood ; Interleukins ; blood ; Male ; Middle Aged ; Minor Histocompatibility Antigens ; Rhinitis, Allergic ; blood ; Young Adult