Cytomegalovirus pneumonia after allogeneic hematopoietic stem cell transplantation / 中华内科杂志

To compare the clinical features and prognosis in patients with cytomegalovirus pneumonia from other pneumonia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 118 patients with pulmonary complications after allo-HSCT from March 2016 to June 2019 were analyzed retrospectively, who were divided into cytomegalovirus (CMV) pneumonia group ( n=34) and the non-CMV pneumonia group ( n=84). Compared with non-CMV pneumonia group, CMV pneumonia group presented earlier median onset time (1.8 vs.6.0 months, P=0.015) after allo-HSCT, more dyspnea (41.2% vs. 19.0%, P=0.012), hypoxemia (38.2% vs. 13.1%, P=0.006), and interstitial pneumonia (82.4% vs. 23.8%, P<0.01).The incidence of CMV-viremia and serum viral load in CMV pneumonia group were significantly higher than those in non-CMV pneumonia group. Consistently, and the development of mixed infection in CMV pneumonia group was higher than that of non-CMV pneumonia group (41.2% vs. 16.7%, P=0.013). The median follow-up time was 12.8 (0.4-46.5) months. The 1-year attributable mortality in CMV pneumonia group was significantly higher than that in non-CMV pneumonia group (26.5% vs. 10.7%, P=0.004), while the 1-year overall survival rate was significantly lower than that in non-CMV pneumonia group (61.8% vs. 85.7%, P=0.001). Reduced-intensity conditioning (RIC)( P=0.036), high flow ventilation ( P=0.033) and negative CMV-viremia ( P=0.009) were unfavorable prognostic factors of patients with CMV pneumonia. Compared with those with non-CMV pneumonia, patients with CMV pneumonia had more characteristic clinical manifestations and imaging features. However, due to the higher incidence of mixed infections, the causes of pneumonia need to be identified by bronchoscopic alveolar lavage. In conclusion, patients with CMV pneumonia have worse clinical outcome. RIC, high flow ventilation and negative CMV-viremia are adverse prognostic factors for CMV pneumonia.

Clinical study of 23 cases with pneumocystis pneumonia after allogeneic hematopoietic stem cell transplantation / 中华急诊医学杂志

Objective:To analyze the risk factors,clinical characteristics and prognosis of the pneumocystis pneumonia(PCP) that is one of the severe pulmonary complications after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:The clinical features,laboratory data,treatment and outcomes of patients with PCP after allo-HSCT in our hospital from January,2016 to January,2021 were retrospectively collected and analyzed.Results:Twenty three cases who met the clinical diagnostic criteria of PCP were enrolled. The median time of diagnosed as PCP after transplantation was 221 days. The computed tomography (CT) of chest indicated diffuse ground glass opacity.The median of β-1,3-D glucan consentration was 894.25 ng/L, and 91.3% of the cases were over 60 ng/L.The lymphocyte count in 60.9% cases was lower than 1×10 9/L;CD4 +T lymphocyte count in 65.2% of patients was less than 200/μL. Pneumocytis sequences of mNGS were positive in all 21 cases.15 patients were complicated with mixed infection.All patients were treated with TMP-SMX,18 patients were cured and 5 patients died. Conclusions:Patients with PCP after allo-HSCT progresses rapidly, and which is usually with multiple infections. Serum β-1,3-D glucan concentration increase contributes to the diagnosis of PCP.And mNGS in alveolar lavage fluid is highly sensitive to Pneumocystis, which helps patients get treatment in time, so as to reduce mortality.Patients with respiratory failure progressing to a need for mechanical ventilation and high flow oxygen inhalation suggest a poor prognosis.

Metformin Induces Apoptosis of Human Multiple Myeloma Cell U266 through the Mitochondrial Apoptotic Pathway / 中国实验血液学杂志

<p><b>OBJECTIVE</b>Metformin (Met) can inhibit the proliferation of tumor cells in vitro, its effects on multiple myeloma and action mechanisms have been not yet understood. The purpose of this study was to investigate the effect and molecular mechanism of metformin on human myeloma cells U266.</p><p><b>METHODS</b>U266 cells were treated with different concentration of Met, the MTT was used to detect cell proliferation, the PI staining was used to detect the cell cycle, and the protein expression of BCL-2 family and the release of cytochrome C were assessed by Western blot.</p><p><b>RESULTS</b>Metformin could inhibit the proliferation of U266 cell in a time- and concentration- dependent manner. The U266 cells were arrested in G/G phase after metformin treatment for 48 h, as compared with non-treated U266 cells. The proteins expression of BCL-2 and BCL-XL was down-regulated and the protein expression of BAX was up-regulated. The released of cytochrome C from mitochondria to cytoplasm was increased, and protein splicing of PARP was also enhanced.</p><p><b>CONCLUSION</b>Metformin can inhibit the cell proliferation and induce U266 cell apoptosis through the mitochondrial apoptotic pathway.</p>

Effect of acoustic stimulus intensity on air-conducted sound elicited ocular vestibular-evoked myogenic potential and cervical vestibular-evoked myogenic potential / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of acoustic stimulus intensity on air-conducted sound elicited ocular vestibular- evoked myogenic potential (oVEMP) and cervical vestibular-evoked myogenic potential (cVEMP) in normal young Chinese subjects.</p><p><b>METHODS</b>Thirty-five normal subjects aged 4-40 years (20.80∓8.89 years), including 16 males and 19 females, were recruited for conventional oVEMP and cVEMP examinations. The responses obtained from each side using 500 Hz tone bursts were divided into 6 groups according to different sound intensities (100, 95, 90, 85, 80 and 75dB nHL). The response rate and normal parameters of each stimulus intensity group were calculated.</p><p><b>RESULTS</b>As the acoustic stimulus intensity decreased, the oVEMP response rate decreased from 100% in both 100 dB nHL and 95dB nHL groups to 97.14% (90 dB nHL), 54.29% (85 dB nHL), 14.29% (80 dB nHL), and 2.86% (75 dB nHL), and the response rate of cVEMP, 100% in both 100 dB nHL and 95dB nHL groups, was lowered to 97.14% (90 dB nHL), 84.29% (85 dB nHL), 38.57% (80 dB nHL) and 8.57% (75 dB nHL). The response rate and the parameters were comparable between 100 and 95 dB nHL groups.</p><p><b>CONCLUSION</b>As the acoustic stimulus intensity decreases, both oVEMP and cVEMP show decreased response rate and amplitude. For Chinese subjects under 40 years of age, we recommend 95dB nHL as the maximum initial stimulus intensity in VEMPs test.</p>

Efficacy and safety of the HAA regimen as induction chemotherapy in 236 de novo acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of the HAA regimen (homoharringtonine, cytarabine and aclarubicin) as induction chemotherapy in de novo acute myeloid leukemia (AML).</p><p><b>METHODS</b>The efficacy and safety of 236 de novo AML patients who received the HAA regimen as induction chemotherapy were retrospectively analyzed. The complete remission (CR) rate was assayed. Kaplan-Meier method was used to estimate overall survival (OS) and relapse free survival (RFS), and the differences were compared by Log-rank test.</p><p><b>RESULTS</b>The overall CR rate was 78.0%, and 65.7% of the patients attained CR in the first induction cycle. The early death rate was 4.7%. The median followup time was 41(1-161) months. The estimated 5-year OS and 5-year RFS rates were 44.9% and 45.5%, respectively. The CR rates of patients with favorable, intermediate and unfavorable cytogenetics were 92.9%,78.6%and 41.7%, respectively. The 5-year OS of favorable and intermediate group were 61.1% and 45.1%, respectively. The 5- year RFS of favorable and intermediate group were 49.0% and 45.4%, respectively. The median survival time of unfavorable group was only 5 months. The side effects associated with the HAA regimen were tolerable, in which the most common toxicities were myelosuppression and infection.</p><p><b>CONCLUSION</b>The HAA regimen is associated with a higher rate of CR and longer survival time and its toxicity could be tolerated.</p>

Synergistic effect of histone deacetylase inhibitor suberoylanilide hydroxamic acid with imatinib on K562 cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate synergistically killing effect of histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) combined with imatinib on human chronic myeloid leukemia (CML) cell line.</p><p><b>METHODS</b>K562 cells were co-treated with SAHA and imatinib. Cell growth was measured by MTT assay. Apoptosis was determined using Hoechst staining apoptosis detection kit and flow cytometric analysis. Activation of Caspase pathway, expression of Bcr-Abl and its downstream target genes, and expression of anti-apoptotic proteins were detected by Western blot.</p><p><b>RESULTS</b>SAHA synergized the cytotoxicity of imatinib against leukemia K562 cells, concomitantly with increased apoptosis and enhanced activation of Caspase-3, -8 and PRAP. The combination therapy resulted in significantly lower levels of Bcr-Abl,phosphorylated Bcr-Abl compared to treatment with either SAHA or imatinib alone. Furthermore,the co-treatment resulted in down-regulation of anti-apoptotic protein Mcl-1 expression. Also,marked down-regulated expression of JAK2,STAT5,and phosphorylated STAT5 was detected in the combination therapy.</p><p><b>CONCLUSION</b>Combining HDAC inhibitor SAHA with imatinib can kill CML cells synergistically by inhibiting cell growth and inducing apoptosis, which is associated with activation of Caspase pathway and regulation of anti-apoptotic proteins.</p>

Dietary calcium decreases plasma cholesterol level only in female but not in male hamster fed a high cholesterol diet / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the effect of dietary calcium on plasma lipoprotein profile in castrated and ovariectomized hamsters.</p><p><b>METHODS</b>Male, castrated, female and ovariectomized hamsters (n=36 each group) were randomly divided into three sub-groups (n=12) and fed one of the three diets containing 0, 2, and 8 g calcium per kg diet for a period of six weeks. Changes in plasma lipoprotein profile were monitored at the end of week 0, 3 and 6.</p><p><b>RESULTS</b>Plasma total cholesterol (TC), non-high density lipoprotein cholesterol (non-HDL-C), triacylglycerols (TG) and TC/HDL-C were decreased only in intact female and ovariectomized hamsters. In contrast, three levels of dietary calcium had no effect on lipoprotein profiles in both intact male and castrated hamsters.</p><p><b>CONCLUSION</b>Beneficial modification of lipoprotein profile by dietary calcium was gender-dependent at least in hamsters.</p>

The efficacy and safety of HAA regimen as induction chemotherapy in 150 newly diagnosed acute myeloid leukemia / 中华内科杂志

Objective To explore the efficacy and safety of HAA regimen (homoharringtonine,cytarabine and aclarubicin) in the treatment of 150 newly diagnosed adult acute myeloid leukemia (AML).Methods All patients entered the study from May 1999 to June 2008 were treated with HAA regimen. Coxsurvival analysis was used to estimate the survival rate and differences between M1/M2 and M4/M5 were compared with 2-sided log-rank test. Results Out of the 150 patients, 121 (81%) achieved complete remission (CR). After the first course, CR rate was 68%. The CR rates of 97%, 84% and 38% were achieved in patients with favorable, intermediate and unfavorable cytogenetics, respectively. For the patients with CR, the median follow-up time was 16.5 ( 1.5-100.5 ) months, and the estimated 3-year survival rate was 45%. The estimated 3-year relapse free survival rate was 52% for the 121 patients with CR.Conclusions HAA regimen may be an efficacious and safe regimen with a good toleration in the induction therapy for newly diagnosed AML, and a high CR rate could be achieved with only one or two courses.

Research progress on autophagy in hematopoietic malignancies / 浙江大学学报·医学版

Autophagy is a process of bulk degradation of proteins and organelles in cytoplasm.Autophagy has many normal physiological functions in cellular catabolism; therefore is essential for cell homeostasis. In some circumstances autophagy can induces cell death, namely autophagic cell death. Recent studies have suggested that autophagy plays an important role in both normal tissue development and a variety of diseases, including cancer. Therefore, the strategy targeting autophagy pathway may represent a new way of cancer treatment.

Expression of telomere binding factor 2 (TRF2) on leukemia cell lines and primary leukemia cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To detect the expression levels of telomere binding factor 2 (TRF2) on leukemia cell lines and primary leukemia cells.</p><p><b>METHODS</b>The expression of TRF2 mRNA was detected with quantitative real-time RT-PCR in leukemia cell lines and primary leukemia cells. The Western blot analysis was used for the detection of TRF2 protein expression.</p><p><b>RESULT</b>TRF2 was overexpressed in T-cell leukemia cell lines but not in myelogenous leukemia cell lines. Significant higher expression levels of TRF2 were observed in primary leukemia cells from patients with M0 and M1 subtypes of acute myelogenous leukemia (AML) compared with normal control and other subtypes of AML.</p><p><b>CONCLUSION</b>Increased TRF2 expression levels are found in T-cell leukemia cell lines and AML patients with poor prognosis, which suggests that TRF2 expression might be related to the prognosis of leukemia.</p>

HAA regimen as induction chemotherapy for newly diagnosed acute myelogenous leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the outcome of newly diagnosed adult acute myeloid leukemia (AML) patients treated with HAA (homoharringtonine, cytarabine and aclarubicin) regimen and explore the efficacy and safety of this regimen.</p><p><b>METHODS</b>Eighty patients were treated with HAA regimen. The complete remission (CR) rate was observed. Kaplan-Meier method was used to estimate relapse free survival (RFS) rate and the differences were compared with 2-sided log-rank test.</p><p><b>RESULTS</b>Of the 80 patients, 65 (81%) attained CR and the CR rate after the first course of induction was 75%. For the CR patients, the median follow-up was 26 (2 -69) months, and the estimated 3-year overall survival (OS) rate was 51% and the estimated 3-year RFS was 53%. For the AML-M5 and AML-M /M2 patients the CR rate was 74% and 87% and 3 year RFS of CR patients was 75% and 37%, respectively. The CR rate of 100%, 83% and 20% was achieved in patients with favorable, intermediate and unfavorable cytogenetics, respectively. The 3 year OS for favorable and intermediate group was 76% and 50% respectively. The median survival time of unfavorable group was only 6 months.</p><p><b>CONCLUSION</b>HAA regimen is a safe, efficacious, and well-tolerable induction therapy for newly diagnosed AML.</p>

Clinical study of amphotericin B in the treatment of invasive fungal infection in 111 hematological disorder patients with neutrocytopenia / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the differences in clinical therapeutic effect and safety between amphotericin B and its liposome form in treating invasive fungal infection (IFI) in hematological disorder with neutrocytopenia.</p><p><b>METHODS</b>Of 111 patients with IFI, 82 were treated with amphotericin B and 29 with amphotericin B liposome. The mean cumulative dose of amphotericin B was 617 (60-1895) mg and the mean course was 18 (7-60) d, and those for amphotericin B liposome was 925 (140-3420) mg and 13 (7-50) d, respectively.</p><p><b>RESULTS</b>The total effective rates of amphotericin B and its liposome groups were 69% and 58%, respectively (P>0.05). The adverse effect rates of chill and fever in amphotericin B and its liposome groups were 21% and 10% (P>0.05), hypopotassemia 34% and 14% (P=0.03), hepatic impairment 22% and 17% (P>0.05), and renal impairment 9% and 3%, respectively (P>0.05).</p><p><b>CONCLUSION</b>The therapeutic effect for IFI of amphotericin B and its liposome was similar. The severe adverse reaction of amphotericin B liposome was slightly lower than that of amphotericin B.</p>