[Development of a Prognostic Model for Overall Survival Adult Patients with Core Binding Factor Acute Myeloid Leukaemia].

OBJECTIVE: To analyze the factors affecting overall survival (OS) of adult patients with core-binding factor acute myeloid leukemia (CBF-AML) and establish a prediction model. METHODS: A total of 216 newly diagnosed patients with CBF-AML in the First Affiliated Hospital of Zhengzhou University from May 2015 to July 2021 were retrospectively analyzed. The 216 CBF-AML patients were divided into the training and the validation cohort at 7∶3 ratio. The Cox regression model was used to analyze the clinical factors affecting OS. Stepwise regression was used to establish the optimal model and the nomogram. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to evaluate the model performance. RESULTS: Age(≥55 years old), peripheral blood blast(≥80%), fusion gene (AML1-ETO), KIT mutations were identified as independent adverse factors for OS. The area under the ROC curve at 3-year was 0.772 and 0.722 in the training cohort and validation cohort, respectively. The predicted value of the calibration curve is in good agreement with the measured value. DCA shows that this model performs better than a single factor. CONCLUSION: This prediction model is simple and feasible, and can effectively predict the OS of CBF-AML, and provide a basis for treatment decision.

LncRNA SNHG26 promotes gastric cancer progression and metastasis by inducing c-Myc protein translation and an energy metabolism positive feedback loop.

Metastasis is a bottleneck in cancer treatment. Studies have shown the pivotal roles of long noncoding RNAs (lncRNAs) in regulating cancer metastasis; however, our understanding of lncRNAs in gastric cancer (GC) remains limited. RNA-seq was performed on metastasis-inclined GC tissues to uncover metastasis-associated lncRNAs, revealing upregulated small nucleolar RNA host gene 26 (SNHG26) expression, which predicted poor GC patient prognosis. Functional experiments revealed that SNHG26 promoted cellular epithelial-mesenchymal transition and proliferation in vitro and in vivo. Mechanistically, SNHG26 was found to interact with nucleolin (NCL), thereby modulating c-Myc expression by increasing its translation, and in turn promoting energy metabolism via hexokinase 2 (HK2), which facilitates GC malignancy. The increase in energy metabolism supplies sufficient energy to promote c-Myc translation and expression, forming a positive feedback loop. In addition, metabolic and translation inhibitors can block this loop, thus inhibiting cell proliferation and mobility, indicating potential therapeutic prospects in GC.

Adjuvant sintilimab in resected high-risk hepatocellular carcinoma: a randomized, controlled, phase 2 trial.

Hepatocellular carcinoma (HCC), particularly when accompanied by microvascular invasion (MVI), has a markedly high risk of recurrence after liver resection. Adjuvant immunotherapy is considered a promising avenue. This multicenter, open-label, randomized, controlled, phase 2 trial was conducted at six hospitals in China to assess the efficacy and safety of adjuvant sintilimab, a programmed cell death protein 1 inhibitor, in these patients. Eligible patients with HCC with MVI were randomized (1:1) into the sintilimab or active surveillance group. The sintilimab group received intravenous injections every 3 weeks for a total of eight cycles. The primary endpoint was recurrence-free survival (RFS) in the intention-to-treat population. Key secondary endpoints included overall survival (OS) and safety. From September 1, 2020, to April 23, 2022, a total of 198 eligible patients were randomly allocated to receive adjuvant sintilimab (n = 99) or undergo active surveillance (n = 99). After a median follow-up of 23.3 months, the trial met the prespecified endpoints. Sintilimab significantly prolonged RFS compared to active surveillance (median RFS, 27.7 versus 15.5 months; hazard ratio 0.534, 95% confidence interval 0.360-0.792; P = 0.002). Further follow-up is needed to confirm the difference in OS. In the sintilimab group, 12.4% of patients experienced grade 3 or 4 treatment-related adverse events, the most common of which were elevated alanine aminotransferase levels (5.2%) and anemia (4.1%). These findings support the potential of immune checkpoint inhibitors as effective adjuvant therapy for these high-risk patients. Chinese Clinical Trial Registry identifier: ChiCTR2000037655 .

[Adsorption Characteristics of Fluoride in Low-Concentration Water by Aluminum and Zirconium-Modified Biochar].

To deal with problems such as the difficult treatment of low-concentration fluoride-containing water and water pollution caused by excessive fluoride (F-) discharge, aluminum and zirconium-modified biochar (AZBC) was prepared and its adsorption characteristics and adsorption mechanism for low-concentration fluoride in water were studied. The results showed that AZBC was a mesoporous biochar with uniform pore structure. It could rapidly adsorb F- from water and reach adsorption equilibrium within 20 min. When the initial ρ(F-) was 10 mg·L-1and the AZBC dosage was 30 g·L-1, the removal rate was 90.7%, and the effluent concentration was lower than 1 mg·L-1. The pHpzc of AZBC was 8.9, and the recommended pH in practical application was 3.2-8.9. The adsorption kinetics accorded with pseudo-second order kinetics, and the adsorption process accorded with the Langmuir model. The maximum adsorption capacities at 25, 35, and 45℃ were 8.91, 11.40, and 13.76 mg·g-1, respectively. Fluoride could be desorbed by 1 mol·L-1 NaOH. The adsorption capacity of AZBC decreased by approximately 15.9% after 5 cycles. The adsorption mechanisms of AZBC were the combination of electrostatic adsorption and ion exchange.Taking actual sewage as theexperimental object, when the AZBC dosage was 10 g·L-1, the ρ(F-) was reduced to below 1 mg·L-1.

[Clinical Features and Prognosis of Multiple Myeloma Patients with Secondary Primary Malignancies].

OBJECTIVE: To explore the clinical characteristics and prognosis of multiple myeloma(MM) patients with secondary primary malignancies. METHODS: The clinical data of newly diagnosed MM patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2019 were retrospectively analyzed. The patients with secondary primary malignancies were retrieved, and their clinical features and prognosis were evaluated. RESULTS: A total of 1 935 patients with newly diagnosed MM were admitted in this period, with a median age of 62 (18-94) years old, of which 1 049 cases were hospitalized twice or more. There were eleven cases with secondary primary malignancies (the incidence rate was 1.05%), including three cases of hematological malignancies (2 cases of acute myelomonocytic leukemia and 1 case of acute promyelocytic leukemia) and eight cases of solid tumors (2 cases of lung adenocarcinoma, and 1 case each of endometrial cancer, esophageal squamous cell carcinoma, primary liver cancer, bladder cancer, cervical squamous cell carcinoma, and meningioma). The median age of onset was 57 years old. The median time between diagnosis of secondary primary malignancies and diagnosis of MM was 39.4 months. There were seven cases with primary or secondary plasma cell leukemia, the incidence rate was 0.67%, and the median age of onset was 52 years old. Compared with the randomized control group, the ß2-microglobulin level in the secondary primary malignancies group was lower (P=0.028), and more patients were in stage I/II of ISS (P=0.029). Among the 11 patients with secondary primary malignancies, one survived, ten died, and the median survival time was 40 months. The median survival time of MM patients after the secondary primary malignancies was only seven months. All seven patients with primary or secondary plasma cell leukemia died, with a median survival time of 14 months. The median overall survival time of MM patients with secondary primary malignancies was longer than that of the patients with plasma cell leukemia (P=0.027). CONCLUSION: The incidence rate of MM with secondary primary malignancies is 1.05%. MM patients with secondary primary malignancies have poor prognosis and short median survival time, but the median survival time is longer than that of patients with plasma cell leukemia.

[Prognostic Significance of LPCAT1 in Adult Acute Myeloid Leukemia Patients with FAB Subtype M2].

OBJECTIVE: To study the prognostic value of LPCAT1 in acute myeloid leukemia (AML). METHODS: TaqMan-based reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect relative expression of LPCAT1 in 214 newly diagnosed adult AML patients and 24 normal controls. Survival functions were estimated using the Kaplan-Meier method and were compared by the Log-rank test. A Cox proportional hazard regression model was used to identify prognostic factors. RESULTS: The expression level of LPCAT1 in adult AML was 34.37%(1.83%-392.63%), which was significantly lower than 92.81%(2.60%-325.84%) of normal controls (P<0.001). The prognostic significance of LPCAT1 was evaluated in 171 non-acute promyelocytic leukemia patients with complete clinical information and prognostic data. Survival analysis showed that the expression level of LPCAT1 had no significant effect on the prognosis of the whole cohort. However, in AML patients with FAB subtype M2 (AML-M2), the 2-year relapse-free survival (RFS) rate of patients with low LPCAT1 expression was 35.4%(95%CI: 0.107-0.601), which was significantly lower than 79.2%(95%CI: 0.627-0.957) of patients with high LPCAT1 expression (P=0.012). Multivariate analysis showed that low expression of LPCAT1 was an independent risk factor for RFS of AML-M2 patients (HR=0.355, 95%CI: 0.126-0.966, P=0.049). CONCLUSION: In adult AML patients LPCAT1 shows low expression. Low LPCAT1 expression is an independent risk factor for RFS in M2-AML patients.

Machine Learning for Computed Tomography Radiomics: Prediction of Tumor-Infiltrating Lymphocytes in Patients With Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: The aims of the study were to develop and validate a machine learning classifier for preoperative prediction of tumor-infiltrating lymphocytes (TILs) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: In this retrospective study of 183 PDAC patients who underwent multidetector computed tomography and surgical resection, CD4 + , CD8 + , and CD20 + expression was evaluated using immunohistochemistry, and TIL scores were calculated using the Cox regression model. The patients were divided into TIL-low and TIL-high groups. An extreme gradient boosting (XGBoost) classifier was developed using a training set consisting of 136 consecutive patients, and the model was validated in 47 consecutive patients. The discriminative ability, calibration, and clinical utility of the XGBoost classifier were evaluated. RESULTS: The prediction model showed good discrimination in the training (area under the curve, 0.93; 95% confidence interval, 0.89-0.97) and validation (area under the curve, 0.79; 95% confidence interval, 0.65-0.92) sets with good calibration. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for the training set were 0.93, 0.85, 0.90, 0.89, and 0.91, respectively, while those for the validation set were 0.63, 0.91, 0.77, 0.88, and 0.70, respectively. CONCLUSIONS: The XGBoost-based model could predict PDAC TILs and may facilitate clinical decision making for immune therapy.

A New Nomogram for Predicting the Risk of Intracranial Hemorrhage in Acute Ischemic Stroke Patients After Intravenous Thrombolysis.

Background: We aimed to develop and validate a new nomogram for predicting the risk of intracranial hemorrhage (ICH) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT). Methods: A retrospective study enrolled 553 patients with AIS treated with IVT. The patients were randomly divided into two cohorts: the training set (70%, n = 387) and the testing set (30%, n = 166). The factors in the predictive nomogram were filtered using multivariable logistic regression analysis. The performance of the nomogram was assessed based on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analysis (DCA). Results: After multivariable logistic regression analysis, certain factors, such as smoking, National Institutes of Health of Stroke Scale (NIHSS) score, blood urea nitrogen-to-creatinine ratio (BUN/Cr), and neutrophil-to-lymphocyte ratio (NLR), were found to be independent predictors of ICH and were used to construct a nomogram. The AUC-ROC values of the nomogram were 0.887 (95% CI: 0.842-0.933) and 0.776 (95% CI: 0.681-0.872) in the training and testing sets, respectively. The AUC-ROC of the nomogram was higher than that of the Multicenter Stroke Survey (MSS), Glucose, Race, Age, Sex, Systolic blood Pressure, and Severity of stroke (GRASPS), and stroke prognostication using age and NIH Stroke Scale-100 positive index (SPAN-100) scores for predicting ICH in both the training and testing sets (p < 0.05). The calibration plot demonstrated good agreement in both the training and testing sets. DCA indicated that the nomogram was clinically useful. Conclusions: The new nomogram, which included smoking, NIHSS, BUN/Cr, and NLR as variables, had the potential for predicting the risk of ICH in patients with AIS after IVT.

[Gene Mutation and Overexpression of Newly Diagnosed Multiple Myeloma Patients].

OBJECTIVE: To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients. METHODS: Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH). RESULTS: Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression. CONCLUSION: There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.

Prediction of Tumor-Infiltrating CD20+ B-Cells in Patients with Pancreatic Ductal Adenocarcinoma Using a Multilayer Perceptron Network Classifier Based on Non-contrast MRI.

RATIONALE AND OBJECTIVES: Conventional chemotherapy has limited benefit in pancreatic ductal adenocarcinoma (PDAC), necessitating identification of novel therapeutic targets. Radiomics may enable non-invasive prediction of CD20 expression, a hypothesized therapeutic target in PDAC. To develop a machine learning classifier based on noncontrast magnetic resonance imaging for predicting CD20 expression in PDAC. MATERIALS AND METHODS: Retrospective study was conducted on preoperative noncontrast magnetic resonance imaging of 156 patients with pathologically confirmed PDAC from January 2017 to April 2018. For each patient, 1409 radiomics features were selected using minimum absolute contraction and selective operator logistic regression algorithms. CD20 expression was quantified using immunohistochemistry. A multilayer perceptron network classifier was developed using the training and validation set. RESULTS: A log-rank test showed that the CD20-high group (22.37 months, 95% CI: 19.10-25.65) had significantly longer survival than the CD20-low group (14.9 months, 95% CI: 10.96-18.84). The predictive model showed good differentiation in training (area under the curve [AUC], 0.79) and validation (AUC, 0.79) sets. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 73.21%, 75.47%, 0.74, 0.76, and 0.73, respectively, for the training set and 69.23%, 80.95%, 0.74, 0.82, and 0.68, respectively, for the validation set. CONCLUSION: Multilayer perceptron classifier based on noncontrast magnetic resonance imaging scanning can predict the level of CD20 expression in PDAC patients.

Contrast-enhanced computed tomography radiomics and multilayer perceptron network classifier: an approach for predicting CD20+ B cells in patients with pancreatic ductal adenocarcinoma.

PURPOSE: To develop and validate a machine-learning classifier based on contrast-enhanced computed tomography (CT) for the preoperative prediction of CD20+ B lymphocyte expression in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Overall, 189 patients with PDAC (n = 132 and n = 57 in the training and validation sets, respectively) underwent immunohistochemistry and radiomics feature extraction. The X-tile software was used to stratify them into groups with 'high' and 'low' CD20+ B lymphocyte expression levels. For each patient, 1409 radiomic features were extracted from volumes of interest and reduced using variance analysis and Spearman correlation analysis. A multilayer perceptron (MLP) network classifier was developed using the training and validation set. Model performance was determined by its discriminative ability, calibration, and clinical utility. RESULTS: A log-rank test showed that the patients with high CD20+ B expression had significantly longer survival than those with low CD20+ B expression. The prediction model showed good discrimination in both the training and validation sets. For the training set, the area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 0.82 (95% CI 0.74-0.89), 92.42%, 57.58%, 0.75, 0.69, and 0.88, respectively; whereas these values for the validation set were 0.84 (95% CI 0.72-0.93), 86.21%, 78.57%, 0.83, 0.81, and 0.85, respectively. CONCLUSION: The MLP network classifier based on contrast-enhanced CT can accurately predict CD20+ B expression in patients with PDAC.

[The Expression and Significance of Serum Protein ROCK2 in Patients with Chronic Graft-Versus-Host Disease].

OBJECTIVE: To investigate the expression and clinical significance of serum protein ROCK2 in patients with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The patients were divided into cGVHD group and control group (without cGVHD). The expression levels of serum protein ROCK2 were detected by ELISA in patients with or without cGVHD after allo-HSCT. RESULTS: The expression level of ROCK2 in serum of cGVHD patients was significantly higher than those in control group, moreover, the expression level of ROCK2 in severe cGVHD group was significant higher than that in moderate and mild cGVHD group (P<0.001). The expression level of ROCK2 was significantly decreased in the serum of cGVHD patients after treatment（P＜0.01）; the expression level of ROCK2 was significantly higher in the serum of cGVHD patients with lung as the target organ（P＜0.01）. The median survival time of patients with severe cGVHD were significantly shorter than that of patients with mild and moderate cGVHD（P＜0.05）. CONCLUSION: ROCK2 shows certain reference value in the evaluation of severity and prognosis of cGVHD, and may be a new target for the treatment of cGVHD.

[Effect of CDK1 Interferes with the Regulation of PLK1, Aurora B and TRF1 on the Proliferation of Leukemia Cells].

OBJECTIVE: To investigate the effect of CDK1 interference regulation of PLK1, Aurora B and TRF1 on the proliferation of leukemia cells. METHODS: The human myelogenous leukemia cell line HL-60 was selected as the research object, and the effect of TRF1 expression and its changes on cell proliferation and cycle was investigated by regulating intracellular CDK1 expression. The objects were divided into 5 groups, including control group, shRNA-NC group, CDK1-shRNA group, pcDNA group and pcDNA-CDK1 group. RT-PCR was used to detect the CDK1 expression of cells in each group; colony formation was used to detect the proliferation of the cells. Western blot was used to detect the expression of CDK1, PLK1, Aurora B, TRF1, and cyclin p53, p27, cyclinA. RESULTS: The phosphorylation level of PLK1, Aurora B and the expression of TRF1 in the CDK1-shRNA group were significantly down-regulated as compared with those in the control group (P<0.05). Compared with the control group, the cells in CDK1-shRNA group showed lower clone formation rate, the increasing of cycle-associated proteins p53 and p27 and the decreasing of cyclinA expression (P<0.05). It was shown that interfered CDK1 expression could inhibit the proliferation of HL-60 cells and prolong the time that they enter mitosis, thereby extending the cell cycle. Compared with the control group, the overexpressed CDK1 in the pcDNA-CDK1 group made the phosphorylation level of PLK1, Aurora B, and TRF1 expression increase significantly (P<0.05), also the colony formation rate (P<0.05). The cycle-related proteins p53 and p27 was down-regulated, while cyclinA expression was up-regulate significantly (P<0.05). The results indicted that overexpressed CDK1 could stimulate adverse reactions, thereby promoting the proliferation of HL-60 cells and shortening the cell cycle. CONCLUSION: Knocking out CDK1 can inhibit the phosphorylation of PLK1 and Aurora B and negatively regulate TRF1, thereby inhibiting the proliferation of leukemia cells.

Evaluation of economic burden with biologic treatments in Crohn's disease patients: A mirror image study using an insurance database in Japan.

Biologics are recommended in Japan to treat moderate to severe Crohn's Disease (CD). Although CD is associated with high direct costs in Japan, updated information after ustekinumab's approval is unavailable. We aimed to evaluate the healthcare resource utilization (HRU) and associated direct costs from the payer's perspective in Japan. Claims data (2010-2018) were retrospectively analyzed to identify patients with CD. HRU and associated costs were evaluated for 12 months before and after biologic initiation and followed-up till 36 months post-initiation. Outcomes were reported using descriptive statistics. Among the included patients (n = 3,496), 1,783 were on biologics and 1,713 were on non-biologics. Mean (SD) age was 36.4 (13.2) years and patients were predominantly male (76.1%). Patients aged 18-39 years were affected with CD the most (55.3%). Biologic initiation was associated with a reduction in inpatient stay, length of stay, outpatient visits, and associated costs; and an increase in pharmacy costs and total costs after 12 months. Extended follow-up showed a decreasing trend in HRU and costs till 24 months but an increase after 36 months. These findings demonstrated reduction in clinical burden and slight increase in economic burden with biologics. However, indirect costs also need to be evaluated.

Role of quantitative hepatitis B surface antibodies in preventing hepatitis B virus-related hepatitis in patients treated with rituximab.

Hepatitis B virus (HBV) reactivation is a well-known complication after rituximab-based chemotherapy in patients with B cell lymphoma (BCL) who have resolved HBV infection. This retrospective cohort study used electronic medical records from the Kaohsiung Chang Gung Memorial Hospital. There were 128 patients with BCL and resolved HBV infection treated with 1st-line rituximab-containing therapy from 2008 to 2013. No patient received antiviral prophylaxis. Patients with high pretreatment hepatitis B surface antibody (anti-HBs titer ≥100 mIU/mL), had significantly less HBV reactivation (2.0%, 1/49) than patients with low (10-100 mIU/mL, 10.8%, 4/37) or negative anti-HBs (<10 mIU/mL, 23.8%, 10/42) (p = 0.001). No patient in the high group vs. 1 (2.7%) low group vs. 6 (14.3%) negative group developed HBV-related hepatitis (p = 0.002). Patients with high pretreatment anti-HBs have a low risk of HBV-related complications and may not require antiviral prophylaxis. We propose an algorithm for the management of HBV reactivation risk in BCL.

Machine learning for MRI radiomics: a study predicting tumor-infiltrating lymphocytes in patients with pancreatic ductal adenocarcinoma.

OBJECTIVE: To develop and validate a machine learning classifier based on magnetic resonance imaging (MRI), for the preoperative prediction of tumor-infiltrating lymphocytes (TILs) in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: In this retrospective study, 156 patients with PDAC underwent MR scan and surgical resection. The expression of CD4, CD8 and CD20 was detected and quantified using immunohistochemistry, and TILs score was achieved by Cox regression model. All patients were divided into TILs score-low and TILs score-high groups. The least absolute shrinkage and selection operator method and the extreme gradient boosting (XGBoost) were used to select the features and to construct a prediction model. The performance of the models was assessed using the training cohort (116 patients) and the validation cohort (40 patients), and decision curve analysis (DCA) was applied for clinical use. RESULTS: The XGBoost prediction model showed good discrimination in the training (AUC 0.86; 95% CI 0.79-0.93) and validation sets (AUC 0.79; 95% CI 0.64-0.93). The sensitivity, specificity, and accuracy for the training set were 86.67%, 75.00%, and 0.81, respectively, whereas those for the validation set were 84.21%, 66.67%, and 0.75, respectively. Decision curve analysis indicated the clinical usefulness of the XGBoost classifier. CONCLUSION: The model constructed by XGBoost could predict PDAC TILs and may aid clinical decision making for immune therapy.

[Gene Mutation in Acute Lymphoblastic Leukemia by DNA Sequencing].

OBJECTIVE: To analyze the characteristics of gene mutation in adult ALL and its clinical significance. METHODS: Clinical data of 134 primary adult ALL patients and DNA sequencing results of 16 kinds of gene mutation were collected. The characteristic of gene mutation and clinical significances were statistically analyzed. RESULTS: In 31 cases of 134 ALL cases (23.13%) the gene mutations were detected as follows: 19 cases of 114 B-ALL cases (16.67%), 11 cases of 19 T-ALL cases (57.89%) and 1 case of T/B-ALL. The incidence of T-ALL gene mutation was significantly higher than that of B-ALL (χ2=13.574, P<0.01). Twelve gene mutations were found, and the mutation rates was IL7R, NOTCH1, FLT3, TP53, FBXW7, PAX5, IKZF1, CREBBP, JAK3, JAK1, PHF6 and PTEN from high to low. Among 108 non-transplantable follow-up patients there was no significant difference in 1-year overall survival rate (49.7% vs 67.4%) and median non-recurrence survival time (214 days vs 260 days) between the gene mutation group (23 cases, 21.30%) and the non-mutation group(85 cases, 78.70%). There was a significant difference in 1-year survival rate between NOTCH1 mutation group (4 cases, 3.77%) and non-mutation group (102 cases, 96.23%) (50.0% vs 65.8%,χ2=9.840, P<0.01). CONCLUSION: There may be multiple gene mutations in adult ALL patients. IL7R and NOTCH1 are the most common gene mutations and NOTCH1 mutation may indicate poor prognosis. Detection of gene mutations is helpful to understand the pathogenesis of ALL and evaluate the prognosis of adult ALL patients.

[Prognostic Value of CD123 in Acute Myeloid Leukemia Patients with Intermediate Risk in Normal Karyotype].

OBJECTIVE: To investigate the expression of CD123 in patients with acute myeloid leukemia (AML) and its relationship between clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis. METHODS: 365 patients with newly diagnosed AML (except M3) treated in the First Affiliated Hospital of Zhengzhou University were enrolled and retrospective analysis, and multi-parameter flow cytometry was performed to detect the expression of CD123 in myeloid leukemia cell population. CD123≥20% was defined as positive. Clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis of CD123+ and CD123- patients were compared and analyzed. RESULTS: The positive rate of CD123 in 365 newly diagnosed AML patients was 38.9%. Compared with the CD123- group, the white blood cell count (WBC), lactate dehydrogenase (LDH) level and bone marrow blast cell ratio were higher in the CD123+ group, and the ratio of NPM1 and DMNT3a gene mutations and the CBFß-MYH11 fusion gene was significantly increased, while the ratio of CEBPA gene mutation and AML-ETO fusion gene was significantly reduced. The rate of first inducing complete remission and total remission in CD123+ group was significantly lower than that in CD123- group. There was no significant difference in recurrence rate between the two groups (P>0.05). Survival analysis showed that in 77 AML patients with normal karyotype and intermediate risk, the 2-year overall survival (OS) rate and event-free survival (EFS) rate of the CD123+ group were significantly lower than those of the CD123- group. Multivariate analysis showed that CD123 was an independent prognostic risk factor for OS and EFS in AML patients with normal karyotype and intermediate risk. CONCLUSION: CD123 positive indicates that AML patients have higher tumor burden and are more difficult to reach remission. It is an independent risk factor for OS and EFS in patients with normal karyotype and intermediate risk, which is important to evaluate the prognosis of patients with AML without specific prognostic marker.

Cordycipitoid Fungi Powders Promote Mycelial Growth and Bioactive-Metabolite Production in Liquid Cultures of the Stout Camphor Medicinal Mushroom Taiwanofungus camphoratus (Agaricomycetes).

Taiwanofungus camphoratus, a medicinal mushroom indigenous to Taiwan, has attracted the attention of pharmaceutical companies due to its remarkable properties and considerable commercial value. Since it grows slowly and most of its components are chemically unstable, its production and distribution have been problematic. In the present study, cordycipitoid fungi powders of seven species were used to cultivate T. camphoratus, and optimal conditions for biomass production were determined by response surface methodology. The initial liquid medium was enriched with cordycipitoid fungi powders, inoculated with a spore suspension of T. camphoratus, and then incubated on a rotary shaker (120 r/min at 27°C) for 14 days. The effects of cordycipitoid fungi powders on T. camphoratus production were investigated by examining the biomass production of T. camphoratus. The key factors influencing biomass production, as identified by a two-level Plackett-Burman design with eight variables, were (1) powder content of cordycipitoid fungi, (2) glucose content, and (3) bottling volume. Box-Behnken design and response surface analysis were applied to further investigate the mutual interactions among these factors, and to obtain optimal values leading to maximal biomass yields. Levels of triterpenoids, polysaccharides, mannitol, adenosine, and ergosterol were determined as estimates of the medicinal value of T. camphoratus cultured with or without cordycipitoid fungi powders. The results showed that Paecilomyces hepiali, Metacordyceps neogunnii, and Beauveria bassiana promoted mycelial growth of T. camphoratus, with P. hepiali showing the most prominent effect. The optimal conditions promoting maximal biomass production were found to be as follows: 6.93 g/L P. hepiali powder content; 26.48 g/L glucose content; 180.55 mL of bottling volume (in a 500-mL Erlenmayer flask). Under these conditions, the biomass production was increased by 38.32%, from 13.10 to 18.12 g/L. The polysaccharide, mannitol, adenosine and ergosterol contents, but not the triterpenoid contents of T. camphoratus cultured with P. hepiali powder, were noticeably higher than when cultured with no powder (control condition), and were higher than those of the P. hepiali powder itself. These results indicate the feasibility of large-scale fermentation of T. camphoratus to produce valuable substances that may be used in pharmaceutical products.

[Adiponectin Receptor Agonist AdipoRon Inhibits the Proliferation of Myeloma Cells via the AMPK/Autophagy Pathway].

OBJECTIVE: To investigate the inhibitory effect of adiponectin receptor agonist AdipoRon on proliferation of myeloma cell lines and its possible mechanism. METHODS: The myeloma cell lines Sp2/0-Ag14 and MPC-11 were treated with different concentration of AdipoRon. The cell proliferation was detected by CCK-8. Western blot was used to determine the protein level of the signaling pathway. RT-PCR was used to quantify the mRNA copy number of adiponectin receptor AdipoR1 and AdipoR2 in the bone marrow cells from 21 patients with multiple myeloma (MM). Twenty-three normal bone marrow samples were served as control. RESULTS: AdipoRon significantly inhibited the proliferation of MM cell lines Sp2/0-Ag14 and MPC-11 in a concentration-dependent and time-dependent manner. Western blot showed that AdipoRon induced an increase of the expression levels of apoptosis-related proteins cleaved caspase-3 and cleaved PARP. AdipoRon upregulated p-AMPK and its downstream p-ACC in MPC-11. In addition, AdipoRon upregulated LC3-II/LC3-I level and down-regulated the protein level of p62. The expression level of AdipoR1 in MM cells was significantly higher than that in normal controls, and the expression level of AdipoR2 in MM cells was significantly lower than that in normal controls. CONCLUSION: Adiponectin receptors are expressed differentially between MM patients and normal subjects. AdipoRon, an adiponectin receptor agonist, can inhibit myeloma cell proliferation and induce apoptosis, and AMPK/autophagy pathway may be one of its mechanisms.