Research progress of fibroblast growth factor19 subfamily in coronary heart disease / 心血管康复医学杂志

Fibroblast growth factors(FGFs)are a kind of growth factors that widely exist in organisms and are close-ly related to regulating the balance of bile acid,glucose and lipid metabolism,vitamin D and phosphorus in vivo.They regulate a variety of physiological and pathological processes by paracrine or endocrine pathways.In recent years,FGF19 subfamily,a kind of metabolic regulatory factors,including FGF21,FGF23 and FGF19,participate in regulating the balance of bile acid,glucose and lipid metabolism,vitamin D and phosphorus in vivo and play an important role in regulating cardiovascular diseases such as coronary heart disease.It provides new ideas and methods for clinical treatment of coronary heart disease.

Prediction models and the extrapolation effects for water content of surface dead fuels in the typical stand of the Great Xing'an Mountains of China by one-hour time step.

The water content of surface dead fuels is one of the most important indicators for forecasting fire danger and fire behaviors. We employed the timelag equilibrium water content methods (i.e. Nelson and Simard models) and the meteorological variable regression method to continuously measure the water content of surface dead fuels by one-hour time step from September to October in 2010 under Populus davidiana + Betula platyphylla, Picea koraiensis and the cutover lands (Pinus sylvestris var. mongolica + Betula platyphylla) with different canopy densities in Pangu Forestry Bureau, the Great Xing'an Mountains, Heilongjiang Province, China. We established prediction models and obtained prediction errors. The models were also used to extrapolate the water contents of surface dead fuels under other forest stands and the extrapolation accuracy was analyzed. The results showed that the mean absolute error, the mean relative error and the mean square error root of Nelson model (0.0154, 0.104 and 0.0226) were lower than those of Simard model (0.0185, 0.117 and 0.0256). In terms of extrapolation effects, the mean absolute error, the mean relative error and the mean square error root of meteorological variable regression method (0.0410, 0.0300 and 0.0740) were lower than those of Simard model (0.610, 0.492 and 0.846), but they were higher than those of Nelson model (0.034, 0.021 and 0.0660). Such results indicated that the timelag equilibrium moisture content method by one-hour time step, especially Nelson model, was sui-table for the forest stands in the Great Xing'an Mountains. Although extrapolation could not reduce the prediction errors, it could help improve the prediction accuracy and the efficiency of the present models applied to different forest stands or in a larger scale. The modeling and extrapolation errors were closely related to species identity and canopy densities, thus the appropriate timelag equilibrium moisture content methods should be selected according to different forest stands and locations.

Analysis of factors influencing postoperative gastrointestinal function recovery in patients undergoing hyperthermic intraperitoneal chemotherapy / 上海交通大学学报（医学版）

Objective · To investigate the effect of hyperthermic intraperitoneal chemotherapy on postoperative gastrointestinal function recovery in patients with gastrointestinal cancer. Methods · Sixty-two cases of gastrointestinal cancer patients were enrolled who accepted cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Department of General Surgery, Shanghai Public Health Clinical Center, Fudan University, from July 2014 to June 2017. The gastrointestinal function of patients were evaluated according to the I-FEED scoring system. The patients were divided into normal recovery group (I-FEED score＜6, n=38) and delayed recovery group (I-FEED score ≥ 6, n=24). Univariate and multivariate Logistic analyses were performed on characteristic factors that may affect the recovery of postoperative gastrointestinal function including gender, age, presence of diabetes, preoperative albumin, and so on. Results · There were significantly differences in the preoperative serum albumin level (P=0.040), intraoperative bleeding (P=0.044), the time of extraction of the peritoneal cavity drainage tube (P=0.026), the time of urethral tube extraction (P=0.021) and the time of hospitalization (P=0.017) in the two groups of patients with normal or delayed gastrointestinal function recovery. Multivariate Logistic regression results suggested that preoperative serum albumin level may be beneficial for the recovery of postoperative gastrointestinal function (OR=0.84, 95％ CI 0.17-4.27, P=0.041).Conclusion · The preoperative serum albumin level can be used as an independent predictor of postoperative gastrointestinal functional recovery in patients with gastrointestinal cancer after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy.

[Prediction models for ground surface fuels moisture content of Larix gmelinii stand in Daxing'anling of China based on one-hour time step].

By using the equilibrium moisture content-time lag methods of Nelson and Simard and the meteorological element regression method, this paper studied the dynamics of the moisture content of ground surface fine dead fuels under a Larix gmelinii stand on the sunny slope in Daxing' anling with a time interval of one hour, established the corresponding prediction models, and analyzed the prediction errors under different understory densities. The results showed that the prediction methods of the fuels moisture content based on one-hour time step were applicable for the typical Larix gmelinii stand in Daxing' anling. The mean absolute error and the mean relative error of Simard method was 1.1% and 8.5%, respectively, being lower than those of Nelson method and meteorological element regression method, and close to those of similar studies. On the same slopes and slope positions, the fuel moisture content varied with different understory densities, and thus, it would be necessary to select the appropriate equilibrium moisture content model for specific regional stand and position, or establish the fuel moisture content model based on specific stand when the dynamics of fuel moisture content would be investigated with a time interval of one hour.

Effect of Chinese medicine treatment based on pattern identification on cellular immunophenotype of myelodysplastic syndrome / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the influence of treatment based on Chinese medicine pattern identification on cellular immunophenotype of the myelodysplastic syndrome (MDS).</p><p><b>METHODS</b>Sixty patients with MDS were randomly and equally assigned to the treatment group and the control group using a randomized digital table. Thirty patients in each group included 3 risk levels (low, moderate and high risks) with each level 10 patients according to the international prognostic scoring system. The control group was given conventional therapy which was also used in the treatment group. While the treatment group was given Zuogui Pill () and Yougui Pill () for low risk patients; Qingwen Baidu Decoction () and Bazhen Decoction () for moderate risk patients; Gexia Zhuyu Decoction () and Qinghao Biejia Decoction () combined with Shiquan Dabu Decoction () for high risk patients. After the treatment, the differences of overall response rate and immunophenotype (CD13, CD14, CD15, CD33 and CD34) of each group were analyzed.</p><p><b>RESULTS</b>The overall response rate of the treatment group was significantly higher than the control group in low risk and moderate risk patients (P=0.029), there was no statistical differences of overall response rate between the treatment group and the control group in high risk patients (P=0.089). The expressions of CD13, CD14, CD33 and CD34 in all three risk levels of the treatment group were obviously decreased after the treatment, while CD15 in all three risk levels of the treatment group was obviously increased after the treatment (P<0.05 or P<0.01). Meanwhile, the difference values of CD13 and CD33 in low risk level of the treatment group, CD33 and CD34 in moderate risk level of the treatment group as well as CD34 and CD15 in high risk level of the treatment group, were all greater than the control groups and they were statistically significant (P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>It shows a better therapeutic effect if the MDS patients treated with Chinese medicine pattern identification in addition to conventional therapy. Since the treatment may inhibit the malignant clones and improve the dysmaturity of granulocyte differentiation, it is a feasible option in clinical practice.</p>

Role and Significance of T Help Cells 17 in Pathogenesis of Idiopathic Thrombocytopenic Purpura / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the role and significance of T help cells 17(Th17) in pathogenesis of idiopathic thrombocytopenic purpura (ITP).</p><p><b>METHODS</b>Peripheral blood samples from ITP patients and normal controls were examined for Th17 cell proportion by flow cytometry (FCM). Expression of IL-17, IL-23, IL-6 and TGF-β1 in hematoplasma was detected by ELISA. The mRNA expression level of IL-17 and RORγt in peripheral blood mononuclear cells (PBMNC) from patients with ITP and normal controls were measured by RT-PCR technique, and expression levels of pSTAT3 and RORγt proteins were analyzed by Western-blot.</p><p><b>RESULTS</b>Th17 cells in peripheral blood from patients with ITP was greatly increased when compared with normal control group (P<0.05). Expressions of IL-17, IL-23, IL-6 and TGF-β1 in hematoplasma of ITP patients were all significantly higher than those in normal control group (all P<0.01). mRNA expression levels of IL-17 and RORγt in PBMNC from patients with ITP were much higher than those in normal controls (P<0.05). Protein expressions of pSTAT3 and RORγt in PBMNC of ITP patients were greatly increased as compared with those in control (P<0.05).</p><p><b>CONCLUSION</b>Th17 cell subgroup may play a role in incidence and development of ITP, which may participate in the pathogenesis of ITP by increasing Th17 cell proportion and altering the expression level of Th17-related cytokines as well as regulatory and transcriptional factors.</p>

Significance of PLSCR1 in Matrine Induced Differentiation of ATRA Resistant APL Cells / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the expression of phospholipid scramblase 1 (PLSCR1) in matrine (MAT) induced differentiation of all-trans retinoic acid (ATRA) resistant acute promyelocytic leukemia (APL) cells, and to explore its correlation to cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signal pathway.</p><p><b>METHODS</b>NB4 (an APL cell line sensitive to ATRA) and NB4-R1 (a resistant strain of ATRA) were observed as subjects in this study. Effects of combined treatment of 0.1 mmol/L MAT and 1 [mol/L ATRA on the differentiation of two cell lines were detected using nitroblue tetrazolium (NBT) reduction test and flow cytometry (CD11b). Expressions of PML/RARot and PLSCR1 protein/gene were detected using Western blot and Real-time fluorescence quantitative PCR assay. Meanwhile, H89, PKA antagonist, was used to observe cell differentiation antigen and changes of aforesaid proteins and genes.</p><p><b>RESULTS</b>MAT combined ATRA could significantly elevate positive rates of NBT and CD11 b in NB4-R1 cells, and significantly down-regulate the expression of PML/RARapha-fusion protein/gene (P < 0.05, P < 0.01). ATRA used alone could obviously enhance the expression of PLSCRI in NB4 cells at protein and mRNA levels (P < 0.01). But the expression of PLSCR1 was up-regulated in NB4-R1 cells, but with statistical.difference only at the protein level (P <0. 01). In combination of MAT, PLSCR1 protein expression was further elevated in the two cell lines (P < 0.01). Besides, there was statistical difference in mRNA expressions in NB4-R1 cells (P < 0.05). All these actions could be reversed by treatment of 10 micromol/L H89 (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>MAT combined ATRA could significantly induce the differentiation of NB4-R1 cells, and inhibit the expression of PML/RARalpha fusion gene/protein, which might be associated with up-regulating PLSCR1 expression.</p>

Matrine and CYC116 synergistically inhibit growth and induce apoptosis in multiple myeloma cells / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate whether CYC116 can potentiate matrine-dependent growth inhibition and apoptosis in multiple myeloma (MM) cells.</p><p><b>METHODS</b>The dose response relationship of matrine to dexamethasone-resistant and dexamethasone-sensitive MM cells was first established. Myeloma RPMI8226 cells were treated with matrine alone or combined with CYC116 for 24 h. Cell proliferation was measured using an MTT assay and apoptosis induction was evaluated by flow cytometry. Activation of the caspase pathway and expression of apoptosis regulator proteins were detected by Western blotting.</p><p><b>RESULTS</b>Matrine significantly induced growth arrest and apoptosis in both drug-resistant and drug-sensitive MM cells. Treatment with the combination of matrine and CYC116 had a stronger cytotoxic effect on MM cells than did single drug treatments. Enhanced apoptosis observed following the combined treatment of matrine and CYC116 was associated with higher levels of activation of caspase-9, caspase-3, and poly adenosine diphosphate ribose polymerase (PARP) and down-regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1 and the signaling proteins p-Akt and nuclear factor κB (NF-κB).</p><p><b>CONCLUSION</b>CYC116 enhances the growth inhibitory and apoptotic effects of matrine on MM cells.</p>

Treatment of myelodysplastic syndrome by hematopoietic stem cell transplantation combined with Chinese medical syndrome typing: a clinical study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy of treating myelodysplastic syndrome (MDS) by hematopoietic stem cell transplantation (HSCT) combined with Chinese medical syndrome typing.</p><p><b>METHODS</b>From July 2009 to July 2013, 6 MDS patients were treated with allo-HSCT combined with Chinese medical syndrome typing from HLA-identical sibling donors at Department of Hematology, Zhejiang Provincial Hospital of Chinese Medicine. Patients were classified as refractory anemia (RA, 2 cases), refractory anemia with ringed sideroblast (RARS, 1 case), refractory cytopenia with multilineage dysplasia (RCMD, 2 cases), and RA with excess blasts-I (RAEB-I , 1 case). Modified BuCy conditioning regimen was used in all 6 cases. Two patients received bone marrow transplantation (BMT), 1 patient received peripheral blood stem cell transplantation (PBSCT), and 3 patients received BMT + PBSCT. In order to prevent the occurrence of graft-versus-host disease (GVHD), all patients were treated with cyclosporine + methotrexate + mycophenolate mofetil. Different Chinese medical treatment methods (by syndrome typing) were given to patients according to different criticality of international prognostic scoring system (IPSS, 5 at moderate risk and 1 at high risk).</p><p><b>RESULTS</b>All 6 patients successfully reconstructed their hematopoietic system. The time from transplantation to ANC ≥ 0.5 x 10(9)/L and platelet (PLT) ≥ 20 x10(9)/L were 13 (9-15) days and 11 (9-22) days respectively. Main complications were GVHD. Acute GVHD (aGVHD) occurred in 4 cases, 3 cases of grade I and 1 case of grade II, and local chronic GVHD (cGVHD) occurred in 1 patient. All cases survived with median follow-up of 18 (11-58) months. The overall survival (OS) and disease-free survival (DFS) rate were 100%.</p><p><b>CONCLUSIONS</b>HSCT combined with Chinese medical syndrome typing could improve clinical symptoms, reduce transplant as- sociated complications. So it was an effective treatment choice for MDS.</p>

Chemical investigation of the roots of Polygala sibirica L / 中国天然药物

AIM@#To investigate the chemical constituents of the roots of Polygala sibirica L. (Polygalaceae)@*METHOD@#The isolation was performed by solvent extraction and various chromatographic techniques, including silica gel, Sephadex LH-20, ODS, semi-preparative HPLC, and preparative TLC. The chemical structures were elucidated based on extensive spectroscopic analysis, including HR-ESI-MS and 1D- and 2D-NMR spectroscopic data.@*RESULTS@#A total of sixteen compounds, including five xanthones (5, 7-10), five saccharide esters (1, 3, 4, 12, 13), two flavonoids (14, 16), two triterpenoids (11, 15), one phenylpropanoid (6), and one benzophenone glycoside (2) were isolated. Their structures were determined as sibiricose A7 (1), sibiriphenone A (2), polygalatenoside A (3), polygalatenoside C (4), lancerin (5), 3, 4, 5-trimethoxycinnamic acid (6), 6-hydroxy-1, 2, 3, 7-tetramethoxyxanthone (7), 1, 3, 7-trihydroxy-2-methoxyxanthone (8), onjixanthone II (9), 1, 2, 3, 6, 7-pentamethoxyxanthone (10), presenegenin (11), 3'-O-3, 4, 5-trimethoxycinnamoyl-6-O-4-methoxy benzoyl sucrose (12), tenuifoliside C (13), 5, 3'-dihydroxy-7, 4'-dimethoxyflavonol-3-O-β-D-glucopyranoside (14), tenuifolin (15), and rhamnetin 3-O-β-D-glucopyranoside (16).@*CONCLUSION@#Compounds 1 and 2 are two new compounds from P. sibirica.

Research advance on the role of ubiquitin proteasome pathway in acute promyelocytic leukemia / 中国实验血液学杂志

Acute promyelocytic leukemia (APL) is characterized by PML-RARa expression. Ubiquitin proteasome-pathway (UPP) plays a key role in all-trans retinoid acid (ATRA) and arsenic trioxide (ATO)-induced degradation. In addition, the regulations of cell cycle and transcription are also related to this pathway. Deeply studying the role of ubiquitin-proteasome pathway in APL contributes to elucidate the mechanisms of some drugs and explode the clinical therapeutical insight for APL. In this article, the constitution of UPP, the role of UPP-mediated protein modification in APL, the application of ubiquitination-associated drugs in APL are reviewed.

Analysis of clinical features of traditional Chinese medicine symptoms and syndromes of 220 patients with chronic aplastic anemia / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study Chinese medicine (CM) syndrome types of chronic aplastic anemia (CAA) patients and the distribution laws of typical CM symptoms in different genders.</p><p><b>METHODS</b>From June 2002 to June 2012, 220 CAA outpatients/inpatients at Department of Hematology, Zhejiang Chinese Medical Hospital were recruited. Patients' symptoms and signs, as well as four diagnostic information at the first onset were collected. CM syndrome differentiation was performed. The syndrome types and typical symptoms were analyzed.</p><p><b>RESULTS</b>(1) In the 220 CAA patients, there were 121 cases of Shen yang deficiency syndrome (55.0%), 18 of Shen yin deficiency syndrome type (8.18%), 81 cases of Shen yin-yang deficiency syndrome (36.82%). (2) The distribution of typical symptoms: fatigue and shortness of breath (77.12% males and 73.53% females), pale complexion (64.41% males and 57.84% females), low temperature of four limbs (12.71% males and 26.47% females), spontaneous perspiration and night sweating (32.20% males and 26.47% females), dry mouth and throat (6.78% males and 6.86% females), feverish feelings in palms and soles (14.41% males and 20.59% females), loose stool (6.78% males and 2.94% females), petechiae and ecchymosis (42.37% males and 43.14% females).</p><p><b>CONCLUSIONS</b>Shen yang deficiency syndrome was most often seen in CAA patients at the initial diagnosis, followed by Shen yin-yang deficiency syndrome. Shen yin deficiency syndrome was the least seen. In CM symptoms, fatigue and shortness of breath were most common seen, followed by pale complexion, skin petechia and ecchymosis.</p>

Combined use of Chinese medicine with allogeneic hematopoietic stem cell transplantation for severe aplastic anemia patients / 中国结合医学杂志

<p><b>OBJECTIVE</b>To determine the effect of combined treatment with Chinese medicine (CM) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on patients with severe aplastic anemia (SAA).</p><p><b>METHODS</b>Eleven patients were treated with CM plus allo-HSCT. Nine patients received a conditioning regimen consisting of fludarabine (Flu), anti-thymocyte globulin (pig ALG), or anti-lymphocyte globulin (Rabbit ATG) and cyclophosphamide (CY), and two patients received pig ALG and CY. All patients were treated with Kidney (Shen)-reinforcing, blood-activating, and stasis-removing (KBS) herbal preparation beginning at 1 week before transplantation and ending at 8 weeks after transplantation. Chimerism status was assessed by analyzing short tandem repeat (STR) polymorphisms.</p><p><b>RESULTS</b>All patients recovered hematopoietic function and none had graft failure. The median number of days required for the absolute neutrophil count (ANC) increased to >0.5×10(9)/L was 15 days (12-22 days) and for spontaneous platelet recovery to >20×10(9)/L without post-transplantation transfusion was 17 days (15-27 days). Nine patients were long-term survivors and achieved full donor chimerism. The overall cumulative incidence of acute graft versus host disease (GVHD) grades I-II and III-IV was 18.2% (2/11) and 9.1% (1/11), respectively. The overall accumulated incidence of chronic GVHD was 27.3% and all patients had limited chronic GVHD. At a median follow-up time of 32 months (range: 12-97 months), 9 patients were still alive. The estimated 5-year overall survival (OS) rate was 81.8%. The incidence of treatment-related mortality, 2-year post-transplantation, was 18.2%. Two patients died from GVHD after transplantation.</p><p><b>CONCLUSION</b>Treatment with the KBS formulation may reduce the rate of graft failure and treatment-related mortality and improve the rate of OS in SAA patients with allo-HSCT.</p>

Homoharringtonine combined arsenic trioxide induced apoptosis in human multiple myeloma cell line RPMI 8226: an experimental research / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To clarify the effects and mechanisms of homoharringtonine (HHT) monomer therapy or combination therapy with arsenic trioxide (ATO) on human multiple myeloma (MM) cell line RPMI 8226 in in vitro researches.</p><p><b>METHODS</b>Effects of HHT, ATO, and HHT combined ATO on the growth of MM cell line RPMI 8226 were detected using MTT assay. The morphological changes of cell apoptosis were detected by Hoechst staining. The early apoptosis rate was detected using flow cytometry. Expressions of Caspase-3, Caspase-9, poly-ADP-ribose polymerase (PARP), Bcl-2, Mcl-1, Bcl-xl, and AKT protein were detected by Western blot.</p><p><b>RESULTS</b>HHT and ATO inhibited the proliferation of RPM1 8226 cell line in a time- and dose-dependent manner (P < 0.05). Synergistic effects was shown in the combination group (Cl < 1). HHT and ATO induced the apoptosis of RPMI 8226 in a dose-dependent manner with typical morphological changes of apoptosis and higher early stage apoptosis rate. The enhancement in apoptotic induction was seen when two agents were combined. HHT activated expressions of Caspase-3 and PARP in a dose dependent manner at 24 h. HHT at 40 ng/mL and ATO at 8.5 micromol/L could significantly activate expressions of Caspase-3 and Caspase-9, and down-regulate expressions of anti-apoptotic proteins Bcl-xl and Mcl-1. In addition, the combination therapy of HHT at 40 ng/mL and ATO at 8.5 micromol/L inhibited phosphorylation of AKT in a time-dependent manner.</p><p><b>CONCLUSION</b>HTT, ATO, and combination therapy of HHT and ATO induced the apoptosis of RPMI 8226 cell line possibly through activating Caspase pathways, regulating expressions of Bcl-2 families, and inhibiting phosphorylation of AKT.</p>

Efficacy and safety of bevacizumab (BEV) plus chemotherapeutic agents in the treatment of metastatic colorectal cancer, mCRC / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of bevacizumab (BEV) plus chemotherapeutic agents in the treatment of metastatic colorectal cancer (mCRC).</p><p><b>METHODS</b>Seventy-seven mCRC patients received BEV plus 5-Fu type, oxaliplatin or irinotecan-based chemotherapy. The clinical efficacy and bevacizumab-related adverse reactions were observed. The efficacy assessment was conducted after at least 2 cycles of BEV therapy. The adverse reactions were recorded in each therapy cycle. Among the 77 cases, 64 patients had finished the efficacy assessment. The adverse reactions in all patients were assessed.</p><p><b>RESULTS</b>The overall response rate (ORR) of BEV plus chemotherapy regimen was 18.75% (12/64), and the disease control rate (DCR) was 75.0% (48/64). In 27 patients who received the regimen as first-line treatment, the ORR reached 37.0% (10/27), while the DCR was 85.2%. Four patients with potentially resectable lesions became resectable after the regimen and received R0 resection of the liver metastases successfully. Twenty-five patients who received the regimen as second line therapy had poor result with ORR 8.0% and DCR 76.0%. Hypertension was observed in 12 cases, with 8 cases of grade 1, 3 cases of grade 2, 1 case of grade 3. Various bleedings occurred in 24/77 cases (31.2%), all were of grade 1-2, including 17 cases of epistaxis, grade 1 hemorrhoid bleeding in one case, hematuria in 3 case (2 of grade 1, 1 of grade 2), GI bleeding in 2 cases, hemoptysis in 1 case (grade 2), and proteinuria in 4 cases (grade 1). Intestinal perforation occurred in 1 case (0.3%). In two patients who had incomplete intestinal obstruction history appeared exacerbated intestinal obstruction symptoms after the application of BEV plus CPT11 regimen.</p><p><b>CONCLUSIONS</b>BEV plus chemotherapy regimen as first-line treatment can improve the ORR and DCR of mCRC patients. When it was used as second- or later-line therapy, it may display satisfied DCR, although with a poor efficacy. The bevacizumab-related toxicity is mild and can be well tolerated.</p>

Bone marrow angiogenesis in patients presenting with differential Chinese medicine syndrome: correlation with the clinico-pathological features of aplastic anemia / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore differences in bone marrow angiogenesis seen in aplastic anemia (AA) patients presenting with differential Chinese medicine (CM) syndrome, and to correlate these differences with clinical pathology.</p><p><b>METHODS</b>Thirty-five patients were enrolled, including 18 with "yang deficiency syndrome" and 17 with "yin deficiency syndrome." Bone marrow biopsies and serum were collected. Microvessel density (MVD) and positive expression of vascular endothelial-derived growth factor (VEGF) were detected by immunohistochemisty. Hypoxia inducible factor -1α (HIF-1α), and VEGF expression were assayed by enzyme-linked immunoabsorbent assay (ELISA), serum lactate dehydrogenase (LDH) was tested by enzyme method and liquid chip technology was used to detected the expression of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ and tumor necrosis factor (TNF)-α.</p><p><b>RESULTS</b>Counts for leukocytes, absolute neutrophils and platelets in "yin deficiency syndrome" were lower than those found in "yang deficiency syndrome" (P<0.05). MVD and VEGF expression, and the positive rate of CD34 and VEGF in bone marrow were lower in AA, especially in "yin deficiency syndrome" (P<0.01 or P<0.05). "Yin deficiency syndrome" displayed decreased VEGF and LDH expression, and enhanced expression of HIF-1α as compared to "yang deficiency syndrome" (P<0.05). Levels of IL-4 and IL-6 were higher in AA (P<0.01), but IL-10 was decreased (P<0.05). High TNF-α expression was seen in "yang deficiency syndrome" and IFN-γ expression was decreased in "yin deficiency syndrome" as compared with normals (P <0.01 and P<0.05, respectively).</p><p><b>CONCLUSION</b>AA patients have lower MVD than normals, especially in "yin deficiency syndrome." MVD might differentially correlate to disease severity, and could be dependent on bone marrow or serum VEGF expression and LDH. Additionally, IL-2, IL-10, IL-4 and IFN-γ were negatively associated while IL-6 and TNF-α were positively associated with MVD.</p>

Itraconazole for secondary prophylaxis of invasive fungal infection in patients undergoing chemotherapy and stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of itraconazole for secondary prophylaxis of previous proven or probable invasive fungal infection (IFI) in patients undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) in agranulocytosis state.</p><p><b>METHODS</b>A phase IV prospective, open-label, multicenter trial was conducted to evaluate itraconazole (200 mg q12h intravenously d1-2, 200 mg/d) as secondary antifungal prophylaxis in patients (18-65 years old) undergoing chemotherapy or HSCT with previous proven or probable IFI. Itraconazole was started when patients' neutrophils＜1.5 × 10⁹/L, and stopped when chemotherapy patients' neutrophils ＞0.5 × 10⁹/L and stem cell transplant recipients' neutrophils＞1.0 × 10⁹/L. The primary end-point of the study was the incidence of proven, probable or possible IFI.</p><p><b>RESULTS</b>Seventy one patients from November 2008 to September 2010 were enrolled in the trial. The median duration of itraconazole prophylaxis was 14 (4-35) days. No patients died of drug-related toxicity within trial. Five cases occurred IFI during the trial. The cumulative incidence of invasive fungal disease was 7.0%. One patient was withdrawn from the study due to treatment-related adverse events (liver malfunction and severe phlebitis).</p><p><b>CONCLUSION</b>Itraconazole appears to be safe and effective for secondary prophylaxis of systemic fungal infection after chemotherapy and allogeneic HSCT. The observed incidence of 7.0% is considerably lower than the relapse rate reported in historical controls, suggesting that itraconazole is a promising prophylactic agent in this population.</p>

Study on matrine alleviating retinoic acid resistance in acute promyelocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the role of matrine (MAT) alleviating all-trans retinoic acid (ATRA) resistance in acute promyelocytic leukemia (APL) and its mechanism.</p><p><b>METHODS</b>ATRA sensitive strain of APL (NB4) and resistant strain (NB4-R1, NB4-R2) were used in this study. The low toxic dosage of MAT was established by MTT test, and ATRA IC(50) of the cell strains (cultured with or without 0.1 mmol/L MAT) were obtained to confirm the reversal index (RI); the influence of MAT (10, 8, 6, 4, 2, 1, 0.1, 0.01, 0.001 mmol/L) combine with 1 µmol/L ATRA on the differentiation of the three cell strains were observed by nitro blue tetrazolium chloride (NBT) test and morphologic changes. The apoptosis rate of cells treated with different concentration of MAT combined with 1 µmol/L ATRA was tested by flow cytometry with Annexin V/PI staining.</p><p><b>RESULTS</b>(1) The toxicity of MAT to NB4, NB4-R1, and NB4-R2 cells was increased with the concentration, IC(50) value was (0.661 ± 0.035) mmol/L, (0.673 ± 0.132) mmol/L and (0.329 ± 0.020) mmol/L, respectively; (2) After treated with 0.1 mmol/L MAT, the ATRA resistance factor of NB4-R1 decreased markedly (RI = 4.96 ± 1.15), but did not of NB4-R2(RI = 0.66 ± 0.17); (3) The differentiation capacity of NB4 and NB4-R1 was enhanced with increase of MAT, and peaked at 0.1 mmol/L (P < 0.05), but did not of NB4-R2; (4) After treated with MAT, the ATRA (1 µmol/L) induced apoptosis rate in NB4 and NB4-R1 increased significantly (P < 0.05 and P < 0.01, respectively).</p><p><b>CONCLUSION</b>MAT can reverse the ATRA resistance of NB4-R1, which may relate to the effect of MAT on differentiation and apoptosis. Treatment with MAT plus ATRA may exaggerate the cells resistance potency.</p>

Clinical study of standard dose of rituximab for the treatment of refractory primary immune thrombocytopenia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of rituximab on B-lymphocytes and anti-platelet glycoprotein-specific antibodies in patients with refractory primary immune thrombocytopenic (ITP).</p><p><b>METHODS</b>Thirty-one ITP patients with a median age of 36 years (range 16 - 56 years) received solely intravenous rituximab at the dose of 375 mg/m(2) once weekly for consecutive 4 weeks. Lab studies included complete blood count, serum concentrations of IgG, IgM and IgA. CD3(+), CD4(+), CD8(+), CD19(+) and CD20(+) cell numbers were assayed by flow cytometry and anti-platelet glycoprotein-specific antibodies (GPIIb/IIIa, GPIb/IX) were assayed by monoclonal antibody-specific immobilisation of platelet antigens (MAIPA) prior to and following rituximab therapy. The response was evaluated according to the response criteria of international working group of ITP.</p><p><b>RESULTS</b>Complete responses were achieved in 12 cases, response in 7 cases, and no response in 12 cases. Responses were sustained 2 to 28 months (median 6 months) with 4 cases relapsed. After 4 weeks of rituximab therapy, GPIIb/IIIa and GPIb/IX disappeared in responded patients, and CD 19(+)/CD20(+) cells were almost depleted in all patients. As expected, the serum concentrations of IgG, IgM, IgA, and the T cell counts were not changed after therapy. Four patients developed infusion-related reaction, 1 impaired renal function, and 3 secondary infections.</p><p><b>CONCLUSION</b>Rituximab is effective and safe, and the adverse reaction is tolerable.</p>

Treatment of severe aplastic anemia by immunosuppressor anti-lymphocyte globulin/anti-thymus globulin as the chief medicine in combination with Chinese drugs / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the therapeutic effect of combined therapy with Chinese drugs and immuno-suppressors, mainly anti-lymphocyte globulin/anti-thymus globulin (ALG/ATG), for the treatment of severe aplastic anemia (SAA), the efficacy associated factors and adverse effects as well.</p><p><b>METHODS</b>A retrospective analysis was conducted on 65 patients with SAA treated by combined therapy which was supplemented with cyclosporin A, androgen, hematopoietic growth factor, etc.</p><p><b>RESULTS</b>Of the 57 patients followed-up, 26 (45.6%) were basically cured, 15 (26.3%) remitted, and 8 (14.0%) improved markedly, the total effective rate being 85.9%. By separately comparing with a single item of clinical data, it was shown that the therapeutic effectiveness was correlated, to a certain extent, with age, illness duration, neutrophil count, and bone marrow proliferation in patients before treatment, as well as with infection that occurred in the follow-up period. It was obviously higher in patients with peripheral neutrophil count > 0.5 x 10 10(9)/L (P<0.05). Various degrees of serum sickness-like reactions occurred in the treatment of 36 patients, including fever in 36 (63.2%), skin rash in 8 (14.0%), and musculoskeletal pain in 5 (8.8%).</p><p><b>CONCLUSIONS</b>The therapeutic effect of combined therapy with Chinese drugs and ALG/ATG in treating SAA could be affirmed, showing some superiority as compared with Western medicine alone. The patients' age, duration of illness, neutrophil count, and bone marrow proliferation before treatment, and degree of infection that occurred could affect the therapeutic efficacy to a certain extent. Adverse reactions resulting from the combined therapy are less, showing the toxicity reducing and effect enhancing action of Chinese drugs.</p>