Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）.@*METHODS@#A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed.@*RESULTS@#A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients.@*CONCLUSION@#VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.

Establishment and Clinical Significance of Prognostic Nomogram Model for Diffuse Large B-Cell Lymphoma Based on Immunohistochemistry Markers and International Prognostic Index Scores / 中国实验血液学杂志

OBJECTIVE@#To retrospectively analyze clinical characteristics and survival time of patients with diffuse large B-cell lymphoma (DLBCL), detect prognosis-related markers, and establish a nomogram prognostic model of clinical factors combined with biomarkers.@*METHODS@#One hundred and thirty-seven patients with DLBCL were included in this study from January 2014 to March 2019 in the First Affiliated Hospital of Nanchang University. The expression of GCET1, LMO2, BCL-6, BCL-2 and MYC protein were detected by immunohistochemistry (IHC), then the influences of these proteins on the survival and prognosis of the patients were analyzed. Univariate and multivariate Cox regression analysis were used to gradually screen the prognostic factors in nomogram model. Finally, nomogram model was established according to the result of multivariate analysis.@*RESULTS@#The positive expression of GCET1 protein was more common in patients with Ann Arbor staging I/II (P =0.011). Compared with negative patients, patients with positive expression of LMO2 protein did not often show B symptoms (P =0.042), and could achieve better short-term curative effect (P =0.005). The overall survival (OS) time of patients with positive expression of LMO2 protein was significantly longer than those with negative expression of LMO2 protein (P =0.018), though the expression of LMO2 protein did not correlate with progression-free survival (PFS) (P >0.05). However, the expression of GCET1 protein had no significant correlation with OS and PFS. Multivariate Cox regression analysis showed that nomogram model consisted of 5 prognostic factors, including international prognostic index (IPI), LMO2 protein, BCL-2 protein, MYC protein and rituximab. The C-index applied to the nomogram model for predicting 4-year OS rate was 0.847. Moreover, the calibrated curve of 4-year OS showed that nomogram prediction had good agreement with actual prognosis.@*CONCLUSION@#The nomogram model incorporating clinical characteristics and IHC biomarkers has good discrimination and calibration, which provides a useful tool for the risk stratification of DLBCL.

Clinical Characteristics of Liver Dysfunction in Patients with Hemophagocytic Syndrome / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical feature of liver injury in patients with hemophagocytic syndrome (HPS).@*METHODS@#The clinical data of 92 patients with HPS in our hospital were analyzed retrospectively, and the characteristics of hepatic lesion and its relationship with prognosis in HPS patients were explored.@*RESULT@#92 cases of HPS showed different degrees of liver dysfunction from mild to moderate. The clinical parameters of liver dysfunction included the increased level of LDH (89.13%), AST (64.13%), TBIL (59.78%) and decreased level of ALB (90.22%). Moreover, 76.09% and 67.39% of the patients had the prolonging of APTT and PT respectively. The ALB level of patients in rheumatoid immune group were higher than that in infection, maglinancy and unexplained groups, all with statistically and significant difference (P＜0.05, P＜0.05 and P＜0.01), the ALB level of patients in infection group were statistically and significantly higher than that in unexplained group (P＜0.01). The Fbg level of patients in infection group were lower than that in maglinancy group, unexplained group and rheumatoid immune group, all the differences were statistically significant (P＜0.05, P＜0.01 and P＜0.05). Child-Pugh grading was further carried out in HPS patients with liver disfunction. Survival time of the patients grade A was significantly higher than that of grade B and C of patients. Univariate analysis showed that the patients with LDH≥2000 U/L, ALB＜30 g/L and PT≥15.1 s had a survival time inferior to control patients (P＜0.05, P＜0.01 and P＜0.01, respectively). Multivariate analysis showed that ALB＜30 g/L was an independent adverse prognostic factor for these patients (P＜0.01).@*CONCLUSION@#Patients with HPS generally have impaired liver function mainly manifested with elevated LDH and AST levels, and declined ALB level, which may correlate with the disease cause and prognosis. Patients with LDH≥2000 U/L, ALB＜30 g/L and PT≥15.1 s have a poorer prognosis and should be treated as soon as possible.

Determination of 11Kinds of Aminoglycosides in Aquatic Products by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry with Molecularly Imprinted Polymers Solid Phase Extraction / 分析化学

An ultra performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed for the determination of 11 kinds of aminoglycosides (AGs), including paromomycin, spectinomycin, tobramycin, gentamycin, kanamycin, hygromycin B, apramycin, streptomycin, dihydrostreptomycin,amikacin and neomycin in aquatic products. Samples were extracted by phosphate buffer solution, and purified on molecularly imprinted polymers (MIP) solid phase extraction column. After separated by Obelisc R chromatographic column, AGs were detected by UPLC-MS/MS. It showed a good linearity relationship in the AGs concentration range of 1.0-1000 ng/mL with the correlation coefficient R2>0.994. The limit of detection (LOD,S/N≥3) was ranged from 1.0 μg/kg to 10.0 μg/kg,and the limit of quantitation (LOQ,S/N≥10) was ranged from 2.0 μg/kg to 20.0 μg/kg. Besides, the average recoveries presented 78.4%-109.6% with the relative standard deviation (RSD, n=6) of 2.3%-14.9%. This method was successfully applied to the simultaneous determination of 11 kinds of AGs with high sensitivity in aquatic products.

Screening of Chemical Drugs in Fishery Inputs by Ultrahigh Performance Liquid Chromatography-Orbitrap High Resolution Mass spectroscopy / 分析化学

To screen the illegal substances in fishery inputs,we established the database including the precursor and the daughter ions for these possible components by the quadrupole/orbit-trap mass spectrometer,and the retention time of each drug on the same chromatographic column.And then,the extracted and diluted samples were analyzed and the components in the real samples were identified under the same conditions.Chromatographic analysis was performed on an Accucore RP-MS column (100 mm × 2.1 mm,2.6 μm) using gradient elution with 0.1％ formic acid in water and 0.1％ formic acid in acetonitrile as mobile phase.Elutes were ionized through heatable electrospray ionization (HESI) in both positive and negative mode simultaneously.Data acquisition was conducted by Full-scan ddMS2 (TopN) mode,in which the full mass profile for a continuous precursor ion injection and the fragments of each high abundant precursor of targeted were acquired with excellent time and mass resolution.Screening was carried out through comparison of the information of real samples with that of standards in the database,which were processed by software (Tracefinder).The Quantification of each component was analyzed based on the precursor ion chromatography acquired by orbit-trap mass spectroscopy,which showed a good linearity between 0.01-1 μg/mL,with R＞0.98.The method was validated by checking its minimum screening concentration (0.5 mg/L for drugs and 5 mg/L for feedstuffs) and evaluating the recovery after addition of the standard mixture in real samples (＞50％,under the addition of 10 and 100 mg/kg).The results for 68 practical samples demonstrated the effective performance of this method for screening with high-throughput,rapidness and acceptable minimum screening concentration and accuracy,in which 15 of 29 fishery drug samples were screened out for positive components that were not indicated in their labels.

Immunogenicity analysis of a recombinant BCG vaccine strain overexpressing Rv3478 protein / 中华微生物学和免疫学杂志

Objective To construct a recombinant Bacillus Calmette-Guerin ( BCG ) vaccine strain, rBCG::Rv3478-pMV261, expressing the Rv3478 protein of Mycobacterium tuberculosis and to inves-tigate its immunogenicity.Methods The gene fragments encoding Rv3478 antigen were amplified by PCR and then respectively cloned into pMV261 and pET-28a vectors to construct the recombinant expression plas-mids (Rv3478-pMV261 and Rv3478-pET-28a).The Rv3478-pMV261 plasmids were transformed into the BCG cells to construct the rBCG vaccine strains, while the Rv3478-pET-28a plasmids were transformed into Escherichia coli BL21 strains for the expression of Rv3478 protein.Polyclonal antibodies were induced in mice upon the immunization with Rv3478 protein.The rBCG vaccine strains overexpressing Rv3478 protein were screened out with Western blot assay.The C57BL/6 mice were divided into four groups including the PBS treated group, BCG treated group, rBCG::pMV261 ( R0) treated group and rBCG::Rv3478-pMV261 ( R3) treated group.All mice were sacrificed in 4 or 12 weeks after immunization.Enzyme-linked immunos-pot assay ( ELISPOT) , ELISA and flow cytometry analysis were performed to evaluate the induced humoral and cell-mediated immune responses in mice.Results The Rv3478 protein was successfully expressed and could induce polyclonal antibodies in mice.High levels of IFN-γand TNF-αwere detected in mice treated with R3, indicating that the immunization with R3 enhanced the cellular immunity.Moreover, the ratios of CD4+to CD8+T cells and the percentages of CD44+CD62L+T cells were increased in mice upon the immuni-zation with R3.Conclusion The recombinant BCG vaccine strain overexpressing Rv3478 protein could in-duce stronger cell-mediated immune responses in mice.It might be have a great significance as a new tuber-culosis( TB) vaccine strain against TB infection in the future.

Inhibitory effects of parthenolide on the activity of NF-κB in multiple myeloma via targeting TRAF6 / 华中科技大学学报（医学）（英德文版）

This study examined the mechanism of the inhibitory effect of parthenolide (PTL) on the activity of NF-κB in multiple myeloma (MM). Human multiple myeloma cell line RPMI 8226 cells were treated with or without different concentrations of PTL for various time periods, and then MTT assay was used to detect cell proliferation. Cell cycle and apoptosis were flow cytometrically detected. The level of protein ubiquitination was determined by using immunoprecipitation. Western blotting was employed to measure the level of total protein ubiquitination, the expression of IκB-α in cell plasma and the content of p65 in nucleus. The content of p65 in nucleus before and after PTL treatment was also examined with immunofluorescence. Exposure of RPMI 8226 cells to PTL attenuated the level of ubiquitinated Nemo, increased the expression of IκB-α and reduced the level of p65 in nucleus, finally leading to the decrease of the activity of NF-κB. PTL inhibited cell proliferation, induced apoptosis and blocked cell cycle. Furthermore, the levels of ubiquitinated tumor necrosis factor receptor-associated factor 6 (TRAF6) and total proteins were decreased after PTL treatment. By using Autodock software package, we predicted that PTL could bind to TRAF6 directly and tightly. Taken together, our findings suggest that PTL inhibits the activation of NF-κB signaling pathway via directly binding with TRAF6, thereby suppressing MM cell proliferation and inducing apoptosis.

Inhibitory effects of parthenolide on the activity of NF-κB in multiple myeloma via targeting TRAF6 / 华中科技大学学报（医学）（英德文版）

This study examined the mechanism of the inhibitory effect of parthenolide (PTL) on the activity of NF-κB in multiple myeloma (MM). Human multiple myeloma cell line RPMI 8226 cells were treated with or without different concentrations of PTL for various time periods, and then MTT assay was used to detect cell proliferation. Cell cycle and apoptosis were flow cytometrically detected. The level of protein ubiquitination was determined by using immunoprecipitation. Western blotting was employed to measure the level of total protein ubiquitination, the expression of IκB-α in cell plasma and the content of p65 in nucleus. The content of p65 in nucleus before and after PTL treatment was also examined with immunofluorescence. Exposure of RPMI 8226 cells to PTL attenuated the level of ubiquitinated Nemo, increased the expression of IκB-α and reduced the level of p65 in nucleus, finally leading to the decrease of the activity of NF-κB. PTL inhibited cell proliferation, induced apoptosis and blocked cell cycle. Furthermore, the levels of ubiquitinated tumor necrosis factor receptor-associated factor 6 (TRAF6) and total proteins were decreased after PTL treatment. By using Autodock software package, we predicted that PTL could bind to TRAF6 directly and tightly. Taken together, our findings suggest that PTL inhibits the activation of NF-κB signaling pathway via directly binding with TRAF6, thereby suppressing MM cell proliferation and inducing apoptosis.

A cross-sectional study on self-reported health and intention of quitting smoking of smokers in Guangzhou factory workers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the health status and intention of quitting smoking in factory workers, so as to provide scientific evidence for smoking control.</p><p><b>METHODS</b>A cross-sectional survey was carried out on smoking behavior, self-reported health status (SRHS), and intention of quitting smoking in 668 Guangzhou factory workers with different job types. Fagerstrom Test for Nicotine Dependence (FTND) was used on current smokers. Logistic regression model was used to analyze the association of SRHS, difficulty of quitting smoking (DQS) with some risk factors.</p><p><b>RESULTS</b>(1) 65.0% (n = 348) male and 3.0% (n = 4) female workers were ever-smokers. 90.6% of male smokers usually smoked when getting together with friends or smokers, staying at home, or at leisure time, or just after a meal. (2) 10.7% of the daily smokers and ex-smokers had a worse SRHS than the general same-age people, which is significantly higher than 5.1% of the occasional smokers and those who were never smoking. The OR was 2.22 (95% CI 1.08 approximately 4.59) after adjusting age and education. (3) Of male daily smokers, 50.5% ever thought of quitting smoking. The proportions of ever-thought of quitting smoking were 73.3%, 50.0% and 37.2% respectively in those with better, pretty the same and worse SRHS than the general same-age people (P = 0.009). The proportions of DQS self-scored 30 or less, 31 to 60 and 60 or more were 26.9%, 24.9% and 48.2% respectively in male daily smokers. The OR for DQS (self-scored > 30 vs < or =30) increased with increasing number of colleague smoked and worked around, and with nicotine dependence.</p><p><b>CONCLUSION</b>Daily smokers and former smokers have worse SRHS than those who are occasional smokers or never smokers in male workers, and most of those with worse SRHS who ever thought of quitting smoking. The DQS is mainly significantly associated with number of colleague smoking and working around, and with nicotine dependence.</p>

Using 1H-MRS to evaluate the effects of warm ischemia reperfusion injury on the regeneration of hepatic cells in orthotopic transplanted livers in rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the prognostic value of proton magnetic resonance spectroscopy (1H-MRS) in the study of warm ischemia reperfusion injury to the regeneration of hepatic cells of the livers following their orthotopic transplantation in rats.</p><p><b>METHODS</b>A rat orthotopic liver transplantation (OLT) model with warm ischemia, the experimental group, was established and the same was done with a control group but without warm ischemia of the livers. They were studied at 6 time points (6 hours, 1, 3, 7, 14, and 30 days after OLT). All rats took axial T1 weighted and T2 weighted imaging scans and 1H MR spectroscopies.</p><p><b>RESULTS</b>The positive rate of proliferating cell nuclear antigen (PCNA) and the mean peak choline/water ratio in the experimental group were significantly higher than those in the control group and the peak choline /water ratio had a positive correlation with the positive rate of PCNA. Serum ALT and AST increased significantly after OLT, especially during the 6 hour to 3day period. The levels of ALT and AST were markedly higher in the experimental group compared to the control group.</p><p><b>CONCLUSION</b>Warm ischemia reperfusion injury of OLT has a significant effect on the regeneration of hepatic cells, and the choline peak of 1H-MRS can be used to evaluate the regeneration of hepatic cells non-invasively.</p>

A cross-sectional study on smoking behavior and nicotine dependence among workers in Guangzhou / 中华流行病学杂志

Objective To investigate smoking behavior and nicotine dependence (ND), so as to provide evidence for tobacco control in workers. Methods A cross-sectional study to investigate smoking behavior and ND in 668 workers with different job assignment in Guangzhou. Fagerstrom Test for Nicotine Dependence and logistic regression model were used to analyze the association between ND and some risk factors. Results (1) The prevalence of ever-smoking was 65.0 % ( 348/535 ) in men ( 55.5 % daily smokers, 5.4% occasional smokers and 4.1% ex-smokers), and 3.0% (4/133) in women. The prevalence of current smoking for manual workers and safety officers were 67.6 % and 64.5 % respectively.(2) Among daily and occasional smokers, 66.7% and 89.7% of them had low ND respectively. Among daily smokers, ND increased with the duration of smoking. Manual workers and officers had higher ND. Conclusion The prevalence of smoking was relatively high in workers and officers and in men. However,majority of the smokers were with low ND and could be the prioritized target for a primary smoking cessation intervention program.