Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research / 中华血液学杂志

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.

Study on the mechanism of circular permuted tumor necrosis factor-related apoptosis-inducing ligand reversing the resistance to imatinib in chronic myeloid leukemia cells / 白血病·淋巴瘤

Objective:To explore the mechanism of circular permuted tumor necrosis factor-related apoptosis-inducing ligand (CPT) reversing the resistance to imatinib in chronic myeloid leukemia (CML) cells.Methods:Five patients with CML in the Affiliated Hospital of Inner Mongolia Medical University from 2016 to 2020 were selected, and heparinized bone marrow blood samples were collected at the first diagnosis and imatinib resistance phase, and mononuclear cells were isolated. The mononuclear cells collected at the first diagnosis were named A1-E1, and the mononuclear cells collected after imatinib resistance were named A2-E2. Human CML wild-type K562 cell line (K562-W) was given gradually increasing small doses of low-concentration imatinib to obtain imatinib-resistant K562 cells (K562-R). K562-R cells were cultured with 20 μg/L CPT and these cells were set as CPT-K562-R group. The CCK-8 method was used to detect the half inhibitory concentration ( IC50) of cells for imatinib. K562-W and K562-R cells were used to establish CML xenografts nude mice models, then the nude mice were divided into K562-W, K562-R and CPT-K562-R xenograft groups. Imatinib was perfused orally in all three groups, and CPT was injected subcutaneously in the CPT-K562-R group at the same time. The tumor volume of the three groups of nude mice before and 4 weeks after treatment with imatinib, and the survival time of the three groups of nude mice were compared. Western blot was used to detect the changes of tyrosine protein kinase receptor B4 (EphB4) and myeloid cell leukemia protein 1 (Mcl-1) protein levels in bone marrow mononuclear cells, K562 cell line and transplanted tumor tissues of CML patients. Results:The expressions of EphB4 protein in A2-E2 cells of 5 patients with CML were higher than those in A1-E1 cells (all P < 0.01). The IC50 of K562-W, K562-R and CPT-K562-R cells for imatinib were (0.160±0.015) mg/L, (5.450±0.460) mg/L, (0.300±0.035) mg/L, and the difference was statistically significant ( F = 390.65, P < 0.01). In cells of K562-W group, EphB4 and Mcl-1 proteins were expressed at low levels (0.54±0.02 and 0.70±0.08); in cells of K562-R group, the expressions of EphB4 and Mcl-1 proteins were enhanced (3.04±0.11 and 2.88±0.04); in cells of CPT-K562-R group, the expressions of EphB4 and Mcl-1 proteins decreased (0.57±0.03 and 0.38±0.04). Before imatinib treatment, there was no statistically significant difference in the tumor volumes of nude mice among the K562-W, K562-R and CPT-K562-R xenograft groups ( F = 0.39, P = 0.68), suggesting the transplanted tumors formed in nude mice were balanced; after imatinib treatment, the difference in the tumor volumes among the three groups were statistically significant ( F = 26.16, P < 0.01). The survival time of nude mice in the K562-W, K562-R and CPT-K562-R xenograft groups was (18.5±3.3) d, (10.0±2.4) d and (17.5±1.6) d, and the difference was statistically significant ( F = 20.45, P < 0.01). In K562-W xenograft group, both EphB4 and Mcl-1 proteins were expressed at low levels (0.55±0.06 and 0.67±0.06); in K562-R xenograft group, the expressions of EphB4 and Mcl-1 proteins were enhanced (1.95±0.08 and 6.21±0.53); the expressions of EphB4 and Mcl-1 in CPT-K562-R xenograft group decreased (0.59±0.04 and 0.37±0.04) and were close to their expressions in K562-W xenograft group. Conclusion:CPT may enhance the sensitivity of CML to imatinib by inhibiting the expressions of EphB4 and Mcl-1, and this may be a targeted pathway for imatinib therapy.

RBM38 Mediates the Proliferation of Acute Myeloid Leukemia Cells HL-60 by Regulating FZD1 mRNA Stability / 中国实验血液学杂志

OBJECTIVE@#To explore the regulatory function of RNA binding motif protein 38 (RBM38) in human acute myeloid leukemia cells HL-60 and its mechanism.@*METHODS@#The lentivirus carriers of overexpressed and knockdown RBM38 were constructed. After HL-60 cells were transfected, Western blot was used to analyze the expression level of RBM38 in HL-60 cells. The cell proliferation and cycle of HL-60 were detected by CCK-8 assay and flow cytometry assay, respectively. RNA immunoprecipitation coupled real-time PCR (RIP-qPCR) was used to detect the combination of RBM38 with mRNAs. Actinomycin D treatment followed by real-time PCR (AcD-qPCR) was used to detect the effect of RBM38 on the stability of target mRNAs.@*RESULTS@#RBM38 in HL-60 cells was overexpressed or inhibited by lentivirus transduction. Overexpressed RBM38 promoted the cell cycle and proliferation of HL-60, while RBM38 knockdown repressed the two processes. RBM38 showed an interaction with FZD1 mRNA and enhancement of its stability.@*CONCLUSION@#RBM38 can regulate cell proliferation of HL-60 by improving the stability of FZD1 mRNA.

Changes of Serum Biomarkers levels in Early Stage of Alcohol-induced Liver Injury in Rats / 中国实验方剂学杂志

Objective:To investigate the dynamic changes of the biomarkers of alcoholic liver injury, including glutamate dehydrogenase(GLDH), α-glutathione-S-transferase(α-GST), purine nucleotide phosphorylase(PNP), and arginine enzyme 1(Arg1), and clarify whether these indexes can be used as early diagnostic biomarkers for alcoholic liver injury. Method:48 Wistar rats were randomly divided into a blank group and a model group, 24 rats in each group, half male and half female. After fasting but except water for 7 h, 50% ethanol/10 mL·kg-1 was given to the model group by intragastric administration and the same volume of normal saline was administered to the blank group. After 1 h, 50% ethanol was again given for once by intragastric administration according to the previous dosage. In the blank group, the same volume of normal saline was administered. After modeling and administration for 6 d, acute alcoholic liver injury model was established. 3 h after the last intragastric administration of alcohol at day 2, 3, 4, 6, six rats (half male and half female) in each group were randomly selected. All the animals were sacrificed to determine the aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP), bilirubin(TBIL), GLDH, α-GST, PNP, and Arg1 levels. Result:As compared with the blank group, the levels of ALT, AST, ALP, TBIL, GLDH, PNP, α-GST and Arg1 in the model group were significantly different (Pα-GST and Arg1 levels were increased earlier and more significantly than ALT and AST levels. Conclusion:GLDH, PNP, α-GST and Arg1 can be used as biomarkers for early detection of alcoholic liver injury.

Changes of CCl4-induced of Liver Injury in Rats for 24 Hours / 中国实验方剂学杂志

Objective:To replicate the animal model of liver injury in rats by using carbon tetrachloride (CCl4), investigate the dynamic changes of early biomarkers of liver injury, namely glutamate dehydrogenase (GLDH), purine nucleotide phosphorylase(PNP), α-dynamic changes of glutathione-S-transferase (α-GST) and arginase 1(Arg1), and provide experimental evidence for early detection of acute liver injury. Method:Forty-eight Wistar rats were randomly divided into a blank group and a model group. The model group was intraperitoneally injected with 10 mL·kg-1 10% CCl4 olive oil solution, fasting but except water. Animals were sacrificed at 3, 6, 12, and 24 h. The serum liver function alanine aminotransferase(ALT), aspartate aminotransferase (AST), bilirubin (TBIL), alkaline phosphatase (ALP) levels, α-GST, Arg1, GLDH, PNP levels, and liver homogenate superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) levels were then detected. Result:As compared with blank group, the levels of ALT, AST, TBIL, α-GST, Arg1, GLDH, PNP and MDA were increased significantly 3 h after administration, and SOD was decreased significantly(Pα-GST, ARG-, GLDH, TBIL, ALP and MDA were increased significantly, while GSH and SOD were decreased significantly (PPα-GST, Arg1, TBIL, ALP and MDA were significantly increased, while GSH and SOD were significantly decreased (PConclusion:α-GST, Arg1, GLDH and PNP have better sensitivity than traditional liver function test indicators, and can be used for early detection of liver injury induced by CCl4 in rats.

Dynamic Changes of Biomarker Levels in Early Stage of Acetaminophen-induced Liver Injury / 中国实验方剂学杂志

Objective:To determine whether glutathione dehydrogenase (GLDH), purine nucleotide phosphorylase (PNP), α-glutathione-S-transferase (α-GST), and arginase 1 (Arg1) can be used as the early biomarkers of drug-induced liver injury by comparing the changes of traditional biomarkers alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), total bilirubin (TBIL) and potential biomarkers GLDH, PNP, α-GST and Arg1 in acetaminophen (APAP)-induced liver injury model rats. Method:The 48 rats were randomly divided into two groups:blank group and model group. 24 rats in each group, half male and half female. The model group received 1 250 mg·kg-1 APAP solution by intragastric administration to establish the drug-induced liver injury. 6 rats (half male and half female) were randomly selected from each group at 3, 6,12 and 24 h after APAP was given to the model group, to detect the levels of ALT, AST, ALP, TBIL, GLDH, PNP, α-GST, Arg1 in serum and levels of GLDH, PNP, α-GST, Arg1 in liver tissue homogenate at each time point Histopathological changes of liver tissues were observed by hematoxylin-eosin (HE) staining. Result:As compared with the blank group, the levels of ALT, AST, ALP, TBIL, GLDH, PNP, α-GST and Arg1 in serum and liver homogenates were significantly increased in model group(PPα-GST and Arg1 levels in serum and liver tissues of rats in the model group were increased earlier and more significantly than ALT and AST levels. Conclusion:GLDH, PNP, α-GST and Arg1 can be used as biomarkers for early detection of drug-induced liver injury.

Influence of nifedipine combined metoprolol on blood pressure and heart rate in hypertensive patients with coronary heart disease / 心血管康复医学杂志

Objective:To study influence of nifedipine combined metoprolol sustained release tablets on blood pressure and heart rate in hypertensive patients with coronary heart disease (CHD).Methods:A total of 120 hypertensive patients with CHD were selected,randomly and equally divided into nifedipine group (n＝60,received nifedipine monotherapy) and combined treatment group (n＝60,received nifedipine combined metoprolol ),both groups were treated for 12 weeks.Blood pressure,heart rate and indexes of heart rate variability (HRV) were measured and compared between two groups.Results:Compared with before treatment,after treatment,there were significant reductions in 24h mean heart rate (24h HR AV) and mean arterial pressure (MAP),P＝0.001 both,and significant rise in standard deviation of normal to normal RR intervals calculated over the 24h period (SDNN),standard devia-tion of normal to normal RR intervals in all 5min segments of the entire recording (SDANN),root-mean square of differences between successive normal to normal intervals (rMSSD) and adjacent normal RR interval difference ＞50ms stroke accounted for a percentage of 24h total RR interval (PNN50) in two groups,P＜ 0.05 or ＜ 0.01.Compared with nifedipine group after treatment,there were significant reductions in 24hmHR [ (69.24 ± 10.67) beats/min vs.(64.08 ± 8.94) beats/min] and MAP [ (98.06 ± 5.18) mmHg vs.(92.64 ± 4.43) mmHg,P＜0.01 all],and significant rise in SDNN [ (113.89 ± 20.93) ms vs.(124.57 ± 25.34) ms,P＜0.05],SDANN [ (108.31 ± 20.26) ms vs.(119.29 ± 19.37) ms,P＝0.001],rMSSD [ (29.67 ± 11.92) ms vs.(36.23 ± 12.34) ms,P＝0.001] and PNN50 [ (11.25 ± 4.03)% vs.(15.37 ± 4.82)%,P＝0.001] in combined treatment group.There was no significant difference in total effective rate between two groups,P＝ 0.272.Conclusion:Nifedipine combined Metoprolol sustained release tablets possesses significant therapeutic effect on hypertensive patients with CHD.It can effectively control heart rate and blood pressure,and contribute to improving HRV and prognosis,which is worth extending.

Protective effect of amlodipine combined enalapril antihypertension on renal function in aged EH +CHD patients / 心血管康复医学杂志

Objective:To study influence of amlodipine combined enalapril antihypertensive therapy on renal function in aged patients with essential hypertension (EH) complicated coronary heart disease (CHD).Methods:A total of 120 aged EH + CHD patients in our hospital from Feb 2014 to Apr 2016 were enrolled.Patients were randomly and equally divided into amlodipine group,enalapril group and combined treatment group (received amlodipine com-bined enalapril treatment ),all groups were treated for 12 weeks.Total effective rate,standard-reaching condition of blood pressure,urinary albumin excretion rate (UAER),levels of serum creatinine (Scr),cystatin C (CysC) and blood urea nitrogen (BUN) before and after treatment,and incidence of adverse reactions were measured and com-pared among three groups.Results:There was no significant difference in total effective rate among three groups,P＝0.139.Compared with amlodipine group and enalapril group,there was significant reduction in standard-reaching time of blood pressure [ (10.84 ± 2.79) months vs.(10.75 ± 3.31) months vs.(8.20 ± 1.46) months] in com-bined treatment group,P＝0.001 all.Compared with before treatment,after 12-week treatment,there were sig-nificant reductions in UAER,levels of Scr,serum CysC and BUN in amlodipine group and combined treatment group,P＜0.05 or ＜ 0.01;compared with amlodipine group and enalapril group after 12-week treatment,there were significant reductions in UAER [(130.55 ± 12.72) μg/min vs.(135.63 ± 17.64) μg/min vs.(112.25 ± 13.34) μg/min],levels of Scr [ (79.32 ± 6.13) μmol/L vs.(80.25 ± 5.97) μmol/L vs.(68.04 ± 5.56) μmol/L],serum CysC [ (1.14 ± 0.23) mg/L vs.(1.21 ± 0.26) mg/L vs.(0.76 ± 0.17) mg/L] and BUN [ (5.16 ± 1.13) mmol/L vs.(5.79 ± 1.03) mmol/L vs.(4.23 ± 0.56) mmol/L] in combined treatment group,and BUN level of amlodip-ine group was significantly lower than that of enalapril group,P＜0.05 or ＜0.01.There was no significant differ-ence in incidence rate of adverse reactions during treatment among three groups,P＝0.757.Conclusion:Small dose amlodipine combined enalapril is effective on controlling blood pressure in aged EH + CHD patients.Compared with monotherapy,it possesses better protection on renal function with high safety,which is worth extending.

Correlation between expressions of stromal cell-derived factor 1α and osteoprotegerin and bone disease in multiple myeloma / 白血病·淋巴瘤

Objective To understand the correlation of expression levels of serum stromal cell-derived factor 1α (SDF-1α), osteoprotegerin (OPG) and β2microglobulin (β2-MG) in patients with multiple myeloma (MM) with or without myeloma bone disease (MBD). Methods Eighty patients with MM who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2014 to June 2017 were selected; all of the patients met the international diagnostic criteria for MM. According to the symptoms such as bone pain, the patients were divided into group with MBD (45 cases) and group without MBD (35 cases). Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of SDF-1α and OPG, and radioimmunoassay was used to detect the expression of MM major prognostic indicator β2-MG. The MBD score was evaluated in 45 patients selected by random number table after sacroiliac joint X-ray and three-dimensional bone reconstruction. The χ 2test was used to compare the categorical variables; the two independent sample t-test was used to compare the continuous variables that conformed to the normal distribution between two groups, and the Pearson method was used for the correlation analysis. Results The expression level of serum SDF-1α in the group with MBD was significantly higher than that in the group without MBD [0.31±0.17) pg/ml vs. (0.18±0.06) pg/ml], and the difference was statistically significant (t ＝-4.21, P < 0.001). The expression level of serum OPG in the group with MBD was significantly lower than that in the group without MBD [(0.73±0.50) pg/ml vs. (1.08±0.31) pg/ml], and the difference was statistically significant (t＝ 3.62, P< 0.001). Pearson analysis showed that β2-MG level in the group was positively correlated with SDF-1α level (r＝ 0.84, P< 0.001), and negatively correlated with OPG level (r＝ -0.48, P<0.001). The β2-MG level in the group without MBD did not show a correlation with the SDF-1α and OPG levels. Conclusions In the serum of patients with MBD, the expression levels of β2-MG and SDF-1α are increased, and the expression level of OPG is decreased. SDF-1α and OPG may be new clinical biochemical indicators for diagnosis, treatment and prognosis assessment in MBD.

Evaluation of four physical examinations in diagnosis of complete rupture of anterior cruciate ligament / 上海交通大学学报（医学版）

Objective· To estimate the value of four physical examination methods in the diagnosis of anterior cruciate ligament complete rupture. Methods · A retrospective study was conducted on 100 patients who underwent surgical treatment for knee joint injury from July 11, 2016 to June 10, 2017. They received four physical examinations including Lachman test, anterior drawer test, lever sign test and pivot shift test. The results of the arthroscopy inspections were used as gold standard. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, accuracy and other parameter of four physical examinations were comprehensively discussed. Results · Arthroscopic examination confirmed that 81 patients had complete rupture of anterior cruciate ligament. The sensitivities of anterior drawer test, lever test, pivot shift test and Lachman test were 87.7%, 100.0%, 97.5% and 96.3%, and the specificities were 84.2%, 78.9%, 73.7% and 63.2%, respectively. The positive predictive values were 95.9%, 95.3%, 94.0% and 91.8%, while the negative predictive values were 61.5%, 100.0%, 87.5% and 80.0%, respectively. The accuracies were 87%, 96%, 93% and 90%, respectively. The positive likelihood ratios were 5.6, 4.7, 3.7 and 2.6, while the negative ones were 0.1, 0, 0 and 0.1, respectively. Conclusion · Anterior drawer test is the most effective in diagnosing the complete rupture of the anterior cruciate ligament, while lever sign test is the most effective in excluding one. Lever sign test is the most sensitive and easy to operate, especially for fresh bruise, acute injury, limb swelling and obesity, with high diagnostic value.

Progress of miR-214 and miR-135b in multiple myeloma bone disease / 肿瘤研究与临床

Multiple myeloma (MM) originates from malignant plasma cells, leading to multiple destructive lytic bone lesions that occur in more than 80%of MM patients. MicroRNAs have been reported to be involved in the development of bone lesions in MM. However, it is still unclear that microRNAs can be considered as diagnostic and prognostic biomarkers for bone lesions. MiR-214 and miR-135b may participate in the pathogenesis of bone marrow, which has shown a certain guiding significance in its prognosis. This paper will introduce the relationship between miR-214, miR-135b and myeloma bone disease.

The effect and influence factor analysis ofⅠandⅡ stage DLBCL patients who receive radiotherapy after chemotherapy / 中国医学装备

Objective:To study the effect and influence factor analysis of DLBCL patient with early stage who receive radiotherapy after chemotherapy.Methods: 374 cases of patients with DLBCL was selected from January 2010 to December 2015 in our hospital. By random number table method, the patients were divided into CHOP group (n=104), R-CHOP+RT group (n=93), R-CHOP group (n=80), CHOP+RT group (n=97). CHOP chemotherapy was given to all patients, 180 patients received radiotherapy after chemotherapy, and 169 patients received rituximab. Survival rates were compared between the 4 groups.Results: The survival rate of R-CHOP group in 12 months, 24 months, 50 months and 100 months were lower than R-CHOP+RT group, but the difference was not statistically significant in twelfth months(x2=2.02,P>0.05). The differences of 24 months, 50 months and 100 months were statistically significant (x2=4.08,x2=4.03,x2=8.79;P0.05); The survival rate of CHOP group in 50 months and 100th months was lower than CHOP+RT, but the difference was no significant difference (x2=1.62,x2=0.03;P>0.05). Smoking index, whether the use of rituximab, the age associated with the survival of patients, the difference was statistically significant.Conclusion: Early DLBCL patients with R-CHOP and radiotherapy combined treatment can be effective in patients with survival, while the use of rituximab chemotherapy, in addition to smoking on the prognosis of patients with serious adverse effects.

Treatment of distal femur nonunion with bone defect by less invasive stabilization system and fibular strut graft / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the therapeutic effects of less invasive stabilization system distal femur (LISS-DF) combined with fibular struts graft for distal femur nonunions and bone defects.</p><p><b>METHODS</b>A total of 12 patients with distal femur nonunion and bone defect were underwent revision operation with locked plating, plus a nonvascularized autologous fibular strut bone graft from June 2007 to September 2014, including 10 males and 2 females with an average age of (56.2±14.1) years old ranging from 30 to 77 years old. The mean time from the initial trauma to the last revision operation was (16.4±5.5) months (ranged from 9 to 26 months). All cases were atrophic nonunions according to Weber-Cech classification and type B1 (bone loss) according to Paley classification. All patients were followed up and evaluated with clinical and imaging results. The KSS (American Knee Society Score) scores including knee clinical score and knee functional score were compared before and after the treatment.</p><p><b>RESULTS</b>All patients were followed up from 12 to 17 months with an average of (13.7±1.9) months. All nonunions healed with an average time of (6.2±1.3) months (ranged from 4 to 8 months). The average range of movement (ROM) of the knee was improved from (67.1±29.6)° preoperatively to (102.5±13.6)° at the last follow up. KSS scores including knee pain, range of motion, clinical and functional score were significantly different before and after operation. No such complications as infection, hardware loosening or breakage occurred postoperatively.</p><p><b>CONCLUSIONS</b>LIFF-DF fixation and autologous fibular strut bone graft facilitated the successful treatment of distal femur nonunions with bone defects.</p>

Research progress of primary extramedullary plasmacytoma / 国际肿瘤学杂志

Extramedullary plasmacytoma (EMP) is a rare tumor characterized by proliferation of monoclonal plasma cells,often occurs in the head and neck,followed by gastrointestinal and skin.Diagnosis is based on biopsy,which is the only accurate and reliable method.EMP is needed to discriminate with similar diseases.Radiotherapy is the preferred treatment method of EMP,because it has a higher radiation sensitivity.Sometime we can choose comprehensive treatment because of illness need.Hematopoietic stem cell transplantation is not as the preferred treatment option because of transplant rejection.

Chemical constituents from the twigs and leaves of Harrisonia perforate / 药学学报

This study was performed to investigate the chemical constituents in the twigs and leaves of Harrisonia perforate. Six compounds were isolated from the 95% EtOH extract of the twigs and leaves of Harrisonia perforate by silica gel, ODS, Sephadex LH-20 column chromatographies and preparative HPLC. On the basis of chemical properties and spectra data, these compounds were identified as harriperfin E (1), kihadanin A (2), kihadanin B (3), 6α-acetoxyobacunol acetate (4), gardaubryone C (5), and β-sitosterol methyl ether (6), respectively. Compound 1 is a new chromone, and compounds 2-6 are isolated from this plant for the first time.

Efficacy and safety of anagrelide in treatment of essential thrombocythemia: multicenter, randomized controlled clinical trial / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of anagrelide in essential thrombocythemia (ET).</p><p><b>METHODS</b>Patients who diagnosed as ET according to the World Health Organization classification were enrolled. Each patient was assigned to take anagrelide hydrochloride capsule or hydroxyurea tablet by random 1∶1 ratio. Dose of anagrelide started at 2 mg/d, then increased gradually and the maximum dose was 10 mg/d until the platelet counts dropped to (100-400) × 10⁹/L, one month later gradually reduced to maintain dose. The dose of hydroxyurea was 1000 mg/d at beginning, then increased gradually, when platelet counts dropped to (100-400)×10⁹/L and kept for one month, reduced to maintain dose as 10 mg·kg⁻¹·d⁻¹. The observation period was 12 weeks.</p><p><b>RESULTS</b>A total of 222 patients were enrolled in seventeen centers (including 113 patients treated with anagrelide and 109 with hydroxyurea). Therapy efficacy can be evaluated in 198 patients (including 97 patients administered with anagrelide and 101 with hydroxyurea). At 12th weeks of therapy, the hematologic remission rate was 87.63% (85/97) in anagrelide group and 88.12% (89/107) in hydroxyurea group, the differences between the two groups were not significant (P=0.173). Treatment with anagrelide lowered the platelet counts by a median of 393 (362-1 339) × 10⁹/L from a median of 827 (562-1657) × 109/L at the beginning of the observation to 400(127-1130)×10⁹/L after 12 weeks (P<0.001), which were similar to the treatment result of hydroxyurea by a median drop of 398 (597-1846)× 10⁹/L (P=0.982). The median time to achieving response of anagrelide group was 7 (3-14) days, superior to that of hydroxyurea for 21 (14-28) significantly (P=0.003). Frequency of anagrelide related adverse events was 65.49 % (74/113), including cardiopalmus (36.28% ), headache (21.24% ), fatigue (14.16% ) and dizzy (11.50% ).</p><p><b>CONCLUSION</b>Anagrelide was effective in patients with ET which had similar hematologic remission rate to hydroxyurea and could take effect more quickly than hydroxyurea. Incidence of adverse events was undifferentiated between anagrelide and hydroxyurea, but anagrelide treatment had tolerable adverse effects and no hematologic toxicity.</p>

Homoharringtonine contributes to imatinib sensitivity in chronic myeloid leukemia cell lines / 中国肿瘤临床

Objective: To investigate the mechanism responsible for homoharringtonine (HHT), which contributes to imatinib (IM) sensitivity in the chronic myeloid leukemia (CML) cell line. Methods:We established cell lines from a patient with CML at the time of first diagnosis and relapse phase, and designated the cell lines as NPHA1 and NPHA2, respectively. Stable underexpressed EphB4 cells (NPHA2-EphB4-sh) were obtained. Leukemia cell lines were incubated with HHT. The activated signal proteins in cells were tested by Western blot. Results:EphB4 was overexpressed in IM-resistant NPHA2 compared with the NPHA1 cell line. However, the expression of EphB4 mRNA and protein were significantly decreased in knockdown NPHA2-EphB4-sh cells compared with the NPHA2 and NPHA1 (P<0.001) cell lines. NPHA2-EphB4-sh cells were sensitive to IM (IC50:0.93 mg/L), and NPHA2 showed IM re-sistance (IC50 : 5.45 mg/L) (P<0.001). However, co-stimulation with HHT+IM decreased IC50 of NPHA2 cells to 1.17 mg/L (P<0.001). Meanwhile, phospho-Rac1/cdc42 was significantly increased in NPHA2 cells compared with NPHA2-EphB4-sh (P<0.001). HHT blocked the expression of EphB4/RhoA. Conclusion: The overexpression of EphB4 contributed to IM resistance in CML line cells. EphB4/RhoA may be a new marker of IM resistance. HHT with IM yielded more treatment advantages than IM alone by blocking EphB4/RhoA pathways.

Comparison of therapeutic effect between thalidomide with and without alkylating agents on patients with new-onset multiple myeloma / 肿瘤研究与临床

Objective To compare the efficacy and toxicity of thalidomide-COMP (T-COMP) and thalidomide-VAD (T-VAD) regimens in previously untreated multiple myeloma (MM) patients.Methods Forty-nine newly diagnosed MM patients were randomly allocated to either A group (thalidomide-MP/-COMP,19 cases) or B group (thalidomide-VAD,30 cases).All patients received thalidomide 200 mg p.o.daily.Patients in group A received additionally vincristine 0.4 mg i.v.on day 1-4,cyclophosphamide 200 mg i.v.on day 1-4,melphalan 4 mg tid p.o.on days 1-5,prednisone 60 mg p.o.daily on days 1-5.Patients in group B received additionally vincristine 0.4 mg i.v.on day 1-4 and epirubicin 10 mg/m2 i.v.,on day 1-4 and dexamethasone 40 mg p.o.daily on days 1-4,9-12 and 17-20 for the first cycle and on days 1-4 for the next three cycles.Treatment was administered every 28 days.The therapeutic response was evaluated based on the International Myeloma Working Group Criteria (IMWG 2006) after the treatment.The toxicity was graded according to NCI common terminology criteria for adverse events v 3.0.Results On an intention-to-treat basis,at least partial therapeutic response was observed.The rates were 73.7 ％ and 53.3 ％ in group A and B respectively (x2 =2.029,P =0.154).Overall survival (OS) rate at 2 years were 52.6 ％ (10/19) in group A and 53.3 ％ (16/30) in group B,respectively (x2 =2.468,P =0.116).Considering overall toxicity,constipation,peripheral neuropathy,dizziness/somnolence,skin rash and edema were significantly higher in group B compared with group A,but the incidence of toxicities grade 3-4 was low and similar in both arms.Conclusion The overall response rate of T-MP/T-COMP regimen is similar with that of T-VAD regimen,suggesting this regimen cannot be chosen as the first treatment for patients with non-implantation therapy.

Recent advances on treatment of primary central nervous system lymphoma / 白血病·淋巴瘤

Primary CNS lymphoma (PCNSL) is a rare malignancy with peculiar clinical and biologic features,aggressive course,and unsatisfactory outcome.the particular microenvironment of this malignancy,and sanctuary sites where tumor cells grow undisturbed, strongly affects treatment efficacy. The execution of prospective trials is also difficult because of the rarity of the tumor and the impaired general condition and poor performance status of patients. Chemotherapy is indispensable for the treatment of PCNSL. High-dose methotrexate is the most effctive drug.PCNSL is sensitive to irradiation,but responses to radiotherapy alone are short-lived. MTX-based chemotherapy followed by whole-brain radiotherapy prolonged survival but is associated with delayed neurotoxicity especially in patients older than 60 years. A new approach is attempted to treat PCNSL with chemotherapy alone with defered radiotherapy in old patients with similar survival rencenfly. High-dose chemotherapy with autologous stem cell transplantation HDC/ASCT yielded promising results for recurent PCNSL.Clinical investigation with Temozolomide or rituximab have been reported.Further studies with these new drugs are needed.

Therapeutic effects of high-dose dexamethasone combined with thalidomide and bortezomib on renal function in patients newly diagnosed multiple myeloma / 白血病·淋巴瘤

Objective To assess the efficacy of high dose dexamethasone combined with bortezomib and thalidomide in multiple myeloma (MM) patients with acute renal failure.Methods 23 newly diagoosed MM patients with acute renal failure were treated with high dose dexamethasone combined with bortezomib and thalidomide.Results Reversal of renal failure was documented in 58.3 ％ (7/12) of those severe renal failure patients and 81.8 ％ (9/11) of renal failure patients.Renal function was reversed in 69.5 ％ (16/23) of all patients.The total response rate for MM was 60.9 ％ (14/23).The median time to response was 2 (1-5) months. Overall survival (OS) at 3 years was 56.5 ％ and the median survival time was 34.4 months.Conclusion Renal failure was reversible in the majority of newly diagnosed MM patients treated with highdose dexamethasone containing regimens.The addition of novel agents thalidomide and (or) bortezomib is safe and induces a more rapid renal failure reversal compared with routine chemotherapy.