Acta Academiae Medicinae Sinica

ABSTRACT:The diversity of diagnostic criteria of idiopathic thrombocytopenic purpura (ITP) makes it difficult to compare clinical trial results and exchange clinical experiences. To address this issue, an ITP international working group convened a consensus conference in Italy in October 2007, and some new consensuses concerning the terminology, definition, phases,grading of severity, prognosis, and treatment were achived. The treatment of ITP has been dramatically improved along with the introduction of novel therapeutic agents. Rituximab, a monoclonal anti-CD20 antibody that is able to deplete autoantibody-producing B lymphocytes, has been widely applied because of its high efficacy and safety. Recent evidences suggest that decreased platelet production may also contribute to the development of ITP. Therefore, novel thrombopoiesis-stimulating agents such as thrombopoietin-receptor agonists Romiplostim and Eltrombopag have become new therapeutic options for ITP.

ABSTRACT:Objective To investigate fms-like tyrosine kinase 3 (FLT3) mutation in patients with acute lymphoblastic leukemia (ALL) and its clinical significance. Methods FLT3 mutation-internal tandem duplication (FLT3-ITD) and FLT3 mutation in the tyrosine kinase domain (FLT3-TKD) were detected using polymerase chain reaction (PCR) in the genomic DNA of 61 ALL patients and 7 healthy volunteers (as reference group). The PCR products of these patients who were detected with FLT3-ITD or FLT3-TKD were sent for sequence analysis. Results In all these 61 ALL patients，FLT3-ITDs were identified in 2 patients and FLT3-TKD were identified in one patient. Conclusion FLT3-ITD and FLT3-TKD exist in a small proportion of ALL patients.

ABSTRACT:Objective To investigate the effects of gossypol acetate on proliferation and apoptosis in Raji lymphoblastoid cells and explore the possible mechanism. Methods Trypan blue staining and ethylthiazolyldiphenyl-tetrazolium bromide（MTT） assay were performed to measure the effect of gossypol acetate on the growth of Raji cells. The morphologic changes were observed with Wright’s staining assay. Apoptosis was identified by agarose-gel electrophoresis and annexin V-FITC marked flow cytometry (FCM) analysis. The distribution of cell cycle, apoptosis rate, and Bcl-2 protein expression were analyzed by FCM. Caspase-3 activity was detected by colorimetric assay. Results Gossypol acetate inhibited proliferation and induced apoptosis of Raji cells at concentration higher than 5 μmol/L. The effects were both dose- and time- dependent. Cycle analysis indicated the alteration of cell cycle and G0/G1 arrest. The activation of Caspase-3 was observed by colorimetric assay. The results of flow cytometry showed that the down-regulation of Bcl-2 protein expression and the activation of Caspase-3 seemed to occur simultaneously. Conclusion sGossypol acetate can inhibit the growth of Raji cells and induce their apoptosis. The mechanism may be related to the alteration of cell cycle and the down-regulation of Bcl-2 protein expression.

ABSTRACT:Objective To study the genotype distribution and the effects of killer immunoglobulin- like receptors（KIR） and human leukocyte antigen (HLA) classⅠligand on related donor hematopoietic stem cell transplantation （HSCT). MetholdsThe genotypes of donor/ recipient HLA-Cw and donor KIR were determined by polymerase chain reaction-sequence specific primer（PCR-SSP）in 87 cases of related donor HSCT (40 cases were haploidentical HSCT, and the remaining 47 cases were HLA-identital sibling HSCT). Results A1l the donors possessed KIR2DL1, 2DL2/L3, 2DL4, 3DL2, and 3DL3, and 96.6% of donors possessed 3DL1. The rate of activating KIRs varied. 97.7% of the recipients expressed C1, while the rates of C2, Bw4, and HLA-A3/A11 were different. In haploidentical HSCT, KIR-HLA-mismatched group included 34 cases and the matched group included 6 cases. HLA-HLA-mismatched group included 31 cases and the matched group included 9 cases. In matched sibling donor HSCT, KIR-HLA-mismatched group included 42 cases and the matched group included 5 cases. KIR-HLA-mismatched group had higher 2-year disease-free survival (DFS) rate compared with KIR-HLA-matched group ［(71.5±6.5)% vs. (50.0±10.7)%，P＜0.05］. Conclusion sThe rate of activating KIR is lower than inhibitory KIRs. Inhibitory KIR2DL1, 3DL1, and 3DL2 may play key roles in the natural killer cell alloreactivity. The DFS rate is higher in KIR-HLA-mismatched group than in KIR-HLA-matched group in related donor HSCT.

ABSTRACT:Objective To investigate the effects of arsenic pentaoxide（As2O5）on the proliferation and apoptosis of endothelial cells and compare the effect of As2O5 and arsenic trioxide（As2O3）in vitro. Methods Human umbilical vein endothelial cells (HUVEC) were incubated with or without As2O5 or As2O3 for a certain period. The proliferation profile of HUVEC was determined by methyl thiazolyl tetrazolium (MTT) method. The apoptosis of HUVEC was detected by microscopy and flow cytometry (FCM). Results As shown by MTT assay, the viabilities of HUVEC were (72.5±13.8)%, (52.9±6.2)%, (15.0±12.8)%, and (13.8±13.2)%, respectively, in 0.5, 1.0, 5.0, and 10.0 mg/L As2O5 groups, of which the viabilities of HUVEC at 1.0, 5.0, and 10.0 mg/L of As2O5 were significantly lower than controls (P=0.006, 0.007, and 0.008)； however, the viability was not significantly different between 5.0 and 10.0 mg/L As2O5 groups (P=0.119). In 1.0 mg/L As2O5 group, the cell viabilities were (88.4±6.3)%, (53.1±8.8)%, (30.7±7.9)%, and (16.3±4.6)%, respectively, at 24, 48, 72, and 96 h, of which the cell viabilities at 48, 72, and 96 h were significantly lower than controls (P=0.042, 0.025, and 0.012). As2O5-induced apoptosis of HUVEC was observed by phase contrast microscope and flow cytometry with Annexin V/PI staining. After 48 hours of incubation, the IC50s of As2O5 and As2O3 were 1.1 and 0.3 mg/L, respectively. Conclusion sAs2O5 can inhibit the proliferation of HUVEC and the minimum effective concentration is 1 mg/L. Apoptosis is the main way that As2O5 induces the death of HUVEC. The inhibitory effect of As2O5 on HUVEC is weaker than that of As2O3.

ABSTRACT:Objective To investigate the chromosomal abnormalities and evaluate the prognostic value of post-remission chemotherapy in children with t(8;21) acute myeloid leukemia (AML). Methods The diagnosis of AML and its subtyping were performed using morphological,immunological, and cytogenetic methodologies in 79 children. Induction therapies included homoharringtonine and cytarabine (HA), daunorubicin and cytarabine(DA), or homoharringtonine and daunorubicin and cytarabine(HAD).Allogeneic stem cell transplantation or 5-6 cycles of intensive chemotherapy was performed after remission therapy. Results Additional chromosomal abnormalities, including loss of sex chromosome (n=40, 50.6%）, del(9q) (n=9, 11.4%), and complex abnormality (n=7, 8.9%) were identified in 55 patients (69.6%). Three patients had more than 90 chromatosomes and duplicate t(8;21)tetraploid karyotype, and their prognoses were poor. The complete remission (CR) rates were 81.7% (49/60) and 94.8% (55/58), respectively, after one and two cycles of induction chemotherapy. The 3-year event-free survival rate (EFS), disease-free survival rate (DFS), and overall survival rate (OS) were (26.2±6.8)%, (31.3±6.7)%, and (27.6±6.6)%, respectively. Twenty-nine patients received 5 or more cycles of chemotherapy after CR and demonstrated an improved 3-year DFS ［(51.7±9.3)%］. The 3-year DFS was not significantly differently in patients with or without additional abnormalities other than sex chromosome(P=0.36).Post-remission consolidation by high dose cytarabine (HDAC) was significantly superior to standard chemotherapy (66.7% vs. 27.3%，P=0.03). Conclusion sMost children with t(8;21)AML have additional chromosomal abnormalities, although they do not affect the prognosis and long-term survival. Few patients have more than 90 chromatosomes and duplicate t(8;21)tetraploid karyotype, which may result in poor prognosis. Childhood t(8;21) AML usually has high CR rate with relatively good prognosis, and post-remission consolidation by HDAC can improve the survival.

ABSTRACT:Objective To measure the telomere length in patients with bone marrow failure syndrome （BMF） using fluorescence in situ hybridization and flow cytometry （Flow-FISH). Methods Blood samples were collected from 8 patients with BMF. Telomere lengths of mononucleared cells from 8 BMF patients and granulocytes from 3 of these 8 BMF patients (all these 3 patients were suffered from aplastic anemia) were measured using Flow-FISH, and the results were compared with those of normal controls. Telomere lengths were measured by Southern blot in 3 patients, and the results were compared with those obtained from Flow-FISH. Results Among these 8 BMF patients, 5 have decreased telomere length in their mononucleared cells. However, different white cell subgroups, specifically mononucleated cells and granulocytes, have different degree of telomere shortening. In 3 BMF patients who underwent both Flow-FISH and Southern blot, 2 patients had consistent measurement results. Conclusion Flow-FISH can be used for the measurement of telomere length in Chinese patients with BMF.

ABSTRACT:Objective To compare the sensitivity and practicability of modified Bethesda assay and Nijmegen assay in detecting factor Ⅷ (FⅧ) inhibitor. Methods Modified Bethesda assay and Nijmegen assay were used to screen FⅧ inhibitors in 237 patients with hemophilia A. The buffer plus universal coagulation reference plasma (UCRP) was used to establish a standard curve for FⅧ: C assay in modified Bethesda method, instead of Nijmegen plasma plus FⅧ deficiency plasma in Nijmegen method. The cutoff value for positive FⅧ inhibitors is ≥0.6 BU/ml. Results The positive rate of FⅧ inhibitors was 5.5% (n=13) when using modified Bethesda assay and was 8.4% (n=20） when using Nijmegen assay (P>0.05). Conclusion Modified standard Bethesda assay is a convenient and feasible method for detecting FⅧ inhibitors.

ABSTRACT:Objective To compare the efficacy and adverse effects between arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL). Methods The clinical data of 71 patients with newly diagnosed APL were retrospectively analyzed. Two groups were classified according to the induction regimens, namely ATO group (n=41) and ATRA group (n=30). The complete remission (CR) rate and the time to CR were compared between these two groups. Results The CR rate was 97.5% in ATO group and 93.3% in ATRA group (P>0.05). The median time to CR was 29 days (21-45 days) in ATO group, which was significantly shorter than 38.5 days (24-63 days) in ATRA group (P<0.001). Retinoic acid syndrome occurred in 52.9% of patients treated with ATRA, which affected the further use of ATRA. Conclusion sBoth ATO and ATRA have high response rates for newly diagnosed patients with APL. Compared with ATRA, ATO induction therapy has shorter time to achieve CR and less adverse effects, and therefore may be the first-line therapy for APL.

ABSTRACT:Objective To explore the feasible age limits in Chinese elderly patients with non-Hodgkin’s lymphoma (NHL). Methods The clinical data of 507 patients with NHL who were admitted to Peking Union Medical College Hospital (PUMCH) from January 1990 to December 2007 were retrospectively analyzed. They were further followed up by reviewing medical records or by phone. The deadline of follow-up was October 2008. Results The 5-year/8-year overall survival （OS） rates were 64.6%/45.7%，53.0%/44.1%，32.8%/17.5%，40.0%/22.8%, and 19.8%/0, respectively, in patients aged ＜60 years, 60-64 years, 65-69 years, 70-74 years, and ≥75 years. The OS rate was significantly different between patients aged ≥75 years and other age groups, and between patients aged 65-70 years and patients younger than 60 years (P<0.05). Only age， serum albumin， and hemoglobin affected the survival status in elderly NHL patients. Conclusion Sixty-five years can be regarded as the age limit in Chinese NHL patients.

ABSTRACT:Objective To explore the clinical value of blood concentration monitoring during high-dose methotrexate (MTX) treatment. Methods High-dose MTX(1.5-9.0g) was infused to 105 patients with acute lymphoblastic leukemia or lymphoma, and then the blood MTX concentration was measured by fluorescence polarization immune assay( FPIA) 44 hours after the start of administration. The procedure was repeated every 6-12 hours until the concentration was less than 0.1μmol/L. Results Forty-four hours after the start of administration, the blood MTX concentration(CMTX/44h)was ≥5μmol/L in 6 patients（2.8％） and was between 1 and 5μmol/L in 23 patients（10.6％). CMTX/44h≥1μmol/L was more common in patients received 5.0g MTX. No severe adverse event was observed in all patients. Conclusion sBlood MTX concentration is different after high-dose MTX treatment due to individual metabolic differences, and therefore it is clinically important to monitor blood concentration of MTX. Elimination delay is more common in patients receive 5.0g MTX. Application of high-dose MTX therapy under the monitoring of blood MTX concentration is safe and feasible.

ABSTRACT:Objective To evaluate the efficacy and safety of high-dose dexamethasone-based regiments in newly diagnosed multiple myeloma patients with renal impairment. Methods The clinical data of 22 patients with newly diagnosed multiple myeloma patients with renal impairment who received high-dose dexamethasone-based regiments from August 2006 to August 2008 in Peking Union Medical College Hospital were retro- spectively reviewed. Results After receiving a median 4 cycles of high-dose dexamethasone-based regiments, renal impairment was reversed in 7 patients (31.8%) with a median time to reversal of 31 days. Sixteen patients (72.7%) achieved overall response, including 7 patients (31.8%) had complete remission / near complete remission. The grade 3 or 4 adverse events included neutropenia (13.6%), infections (22.7%), peripheral neuropathy (9.1%), and ileus (4.5%). Conclusion The high-dose dexamethasone-based regiments are safe and effective for newly diagnosed multiple myeloma patients with renal impairment.

ABSTRACT:Objective To analyze the clinical features and prognosis of patients with Castleman’s disease (CD). Methods Clinical and pathological data of 49 patients with CD diagnosed in Peking Union Medical College Hospital from January 1990 to December 2007 were retrospectively analyzed. Results In patients with unicentric CD (UCD), hyaline vascular type had the highest percentage (88.2%, 15/17), which was significantly higher than that of either plasma cell type (5.9%, 1/17) or mixed cell type (5.9%, 1/17) (P<0.05). In patients with multicentric CD (MCD), there were no significant differences among the percentages of different histopathologic types. In contrast to patients with UCD, patients with MCD were relatively older and had more typical clinical features, more frequent complications, and more frequent abnormal laboratory results. Twenty patients with UCD achieved complete remission (CR) after surgery, and their complications also disappeared one month later. Twenty-three out of 29 patients with MCD were treated with chemotherapy; only 6 patients achieved CR and 9 achieved partial remission (PR), and the overall response rate was 65.2%. Two patients who initially did not responded to chemotherapy achieved CR after the addition of rituximab. Conclusion sThe clinical features of CD are multifarious and nonspecific, and diagnosis is exclusively depended on histopathology. UCD has a good prognosis after surgery, while MCD often poorly responds to chemotherapy and has a relatively poor prognosis. New drugs and clinical trials are needed to improve the outcome of MCD.

ABSTRACT:Objective To summarize the clinical features of invasive pulmonary fungal infection (IPFI) secondary to malignant blood diseases (MBD). Methods We retrospectively analyzed the clinical data of 52 patients with IPFI secondary to MBD admitted to Peking Union Medical College Hospital from January 1995 to December 2008. Results The incidences of IPFI secondary to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), non-Hodgkin’s lymphoma (NHL), and aplastic anemia(AA) were 4.6%, 3.2%, 2.8%, and 2.5%, respectively. In patients with IPFI secondary to AML, 88.5% (23/26) of the patients suffered from the infections during the non-remission (NR) period (including relapse), and 11.5% (3/26) in the complete-remission(CR) period. In all the patients with IPFI secondary to malignant blood diseases, 86.5% (45/52) of MBD were neutropenic or agranulocytic, and 67.3%(35/52) had been treated with broad-spectrum antibiotics for more than 96 hours before anti-fungal therapy. The total mortality after anti-fungal therapy was 13.7% (7/51). More than half of patients with fluconazol or itraconazole as the first-line therapy had to switch to other medicines because of poor infection control. Conclusion sIPFI secondary to MBD is most common in AML patients. Patients with NR of AML, neutropenia or agranulocytosis, and long-term broad-spectrum anti-biotics usage are susceptible to IPFI. Fluconazol and itraconazole have low efficacy, and other more potent anti-fungal medicines should be considered.

ABSTRACT:Objective To screen for factor Ⅷ inhibitor in patients with hemophilia A (HA) and explore the environmental risk factors for inhibitor development. Methods Totally 265 patients with HA were enrolled, including 107 consecutive inpatients and outpatients in Peking Union Medical College Hospital from April 2003 to April 2007 and 158 patients newly recruited from other hospitals. FⅧ:C activity was measured by one-stage coagulation assay. FⅧ inhibitor was determined using Bethesda method. Results In 265 HA patients, FⅧ inhibitor was detected in 22 patients (8.3%). Nine of them (86.4%) were low responders (inhibitor titers ≤5000BU/L), 3 (13.6%) were high responders (the titers>5000BU/L). The frequency of FⅧ inhibitor was 50% in the patients aged over 50 years，which was significantly higher than those in other age groups（P=0.000). Among 158 newly recruited patients with full clinical data, the frequency of FⅧ inhibitor was 12.8% in patients who had received infusion of FⅧ products for more than 12 doses on average each year, while it was 5.8% in whom the infusion doses were less than 12（P=0.156). The frequency of FⅧ inhibitor was 28.5% in patients with a history of continuous infusion of FⅧ products whereas it was only 1.6% in patients without such history（P=0.000). In patients who exposed to multiple-branded or single-branded FⅧ products, the frequencies of FⅧ inhibitor were 9.3% and 3.9%, respectively（P=0.229). Conclusion The development of factor Ⅷ inhibitor in patients with hemophilia A may be related to the age and the history of continuous infusion of FⅧ products.

ABSTRACT:Objective To explore the effects of selenium and/or iodine deficiency on chondrocyte apoptosis in articular cartilage in rats. Methods Forty-eight Spraguee-Dawley rats were randomly divided into selenium deficiency group, iodine deficiency group, combined selenium and iodine deficiency group, and control group. Chondrocyte apoptosis was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling（TUNEL） method, and Bcl-2 and Bax in articular cartilage were stained by immunohistochemistry in F3 generation of rats. Results In articular cartilage, the positive rate of apoptotic chondrocytes stained by TUNEL in the upper and middle zones in selenium deficiency group, iodine deficiency group, and combined selenium and iodine deficiency group（all P<0.05） were significantly higher than that in control group. The apoptotic chondrocytes were prominent in the middle zone. The positive percentage of chondrocytes apoptosis was not significantly different among these three groups（P>0.05). Compared with the control group, the expressions of both Bcl-2 and Bax were significantly higher in the upper and middle zone in the selenium deficiency group, iodine deficiency group, and combined selenium and iodine deficiency group（all P<0.05）; however, the expressions of Bcl-2 and Bax were not significantly different among these three groups（P>0.05). Conclusion Selenium and/or iodine deficiency may induce chondrocyte apoptosis.

ABSTRACT:Objective To explore the angiogenesis and its maturation of hepatocellular carcinoma (HCC) and its correlation with deoxyhemoglobin parameters R2* and T2* values and the lesion/muscle R2*, T2* ratio by using noninvasive magnetic resonance imaging (MRI). Methods T2*, R2* values and the lesion/muscle R2*, T2* ratio in tumor periphery and center were calculated via series T2* images in a total of 31 patients with surgically and pathologically confirmed HCC. After surgery, all sections were obtained from the specimen periphery in accordance with the MR analyzed areas. Continuous slices of each lesion were stained with hematoxylin-eosin (HE), and immunohistochemical staining was performed in vascular endothelial growth factor（VEGF）, Flk-1, proliferating cell nuclear antigen （PCNA）, CD34, and alpha smooth muscle actin (SMA). The expressions of VEGF, Flk-1, and PCNA index (PI) were evaluated. According to CD34 and SMA, some vascular parameters, including number, mean vessel area, total vessel area, circumference, diameter, distance between adjacent vessels, and variety index of microvessel and mature vessel, were calculated with a computed analysis system. The amounts of arterioles and veinlets, mature vessel index, and mean perfused fraction (mPF) were also recorded. All vessel parameters were compared with the calculated values of MRI. Results R2* value or lesion/muscle R2* ratio decreased and T2* value or the lesion/muscle T2* ratio increased in HCC when compared with hepatic parenchyma (P<0.05); however, those values between lesion periphery and center and among different pathological grades were not significantly different (P>0.05). T2* value and the lesion/muscle T2* ratio significantly decreased when the expression of VEGF was positive (P<0.05). T2* value was negatively correlated with microvessel amount (P=0.047，r=-0.639), while T2* value and the lesion/muscle T2* ratio were positively correlated with mPF (P=0.040，r=0.655; P=0.048，r=0.640, respectively). R2* value was also positively correlated with mean area(P=0.028，r=0.688), total area (P=0.021，r=0.712) or circumference (P=0.037，r=0.663)of microvessel, and negatively correlated with mPF (P=0.024，r=-0.702). Meanwhile, the lesion/muscle R2* ratio was positively correlated with mean area (P=0.043, r=0.647) and circumference (P=0.026, r=0.694)of microvessels. Conclusion R2* or T2* value may be influenced by the variation of deoxyhemoglobin caused by the heterogeneity of angiogenesis.

ABSTRACT:Objective To study the mechanism of endothelial Rho/Rho kinase in extravascular migration of fibrosarcoma cell. Methods We used an in vitro model of fibrosarcoma cell transmigration across a monolayer of human umbilical vein endothelial cell（HUVEC） cultured on collagen gel to observe extravascular migration of fibrosarcoma cells, and then calculated the electrical resistance of HUVEC monolayer and endothelial myosin light chain(MLC) phosphorylation in extravascular migration of fibrosarcoma cells. Results Fibrosarcoma cells migrated through endothelial cells into collagen gel. The electrical resistance of a HUVEC monolayer reduced and endothelial MLC phosphorylation enhanced in the extravascular migration of fibrosarcoma cells. Endothelial Rho inhibitor(C3 transferase) and Rho kinase inhibitor(Y-27632) inhibited the extravascular migration of fibrosarcoma cells and inhibited the reduction of electrical resistance of a HUVEC monolayer and the enhancement of endothelial MLC phosphorylation in extravascular migration of fibrosarcoma cells. Conclusion Endothelial Rho/Rho kinase may regulate fibrosarcoma cell transendothelial migration through MLC phosphorylation.

ABSTRACT:Objective To investigate the effects of emodin on expression of cytokines induced by lipopolysaccharide (LPS) in cultured human corneal fibroblasts in vitro. Methods Primary human corneal fibroblasts of passages 4 were used in this research. Cells were treated with 10 μg/L LPS for 1, 2, 4, or 8 hours, which were pretreated with or without emodin for 30 minutes before LPS challenge. The degeneration of inhibitor of κB-α (IκB-α) and the effect of emodin on it were analyzed by Western blot analysis with a specific antibody. The cellular abundance of the mRNA of interleukin (IL)-6 and IL-8 from corneal fibroblasts under different conditions was determined by reverse transcriptase polymerase chain reaction (RT-PCR). Results Compared with cells without LPS treatment, IκB-α level significantly decreased in every time point after LPS challenge (P<0.01). Emodin inhibited the LPS-induced degeneration of IκB-α by corneal fibroblasts in a dose-dependent manner (P<0.05). Compared with cells without LPS treatment, the expressions of IL-6 and IL-8 mRNA significantly increased in every time point after LPS challenge (P<0.01). At the same time, the expressions of the mRNA of IL-6 and IL-8 induced by LPS in corneal fibroblasts were also inhibited by emodin in a dose-dependent manner (P<0.05). Conclusion Emodin can inhibit the expressions of IL-6 and IL-8 mRNA induced by LPS in corneal fibroblasts, which maybe via inhibiting the degeneration of IκB-α and suppressing the activation of nuclear factor-κB.

ABSTRACT:Objective To explore the efficacy of intraperitoneally injected epirubicin（EPI）-loaded poly(d,l)-lactic acid （PLA）microspheres(MS) alone or combined with free epirubicin(FEPI)in treating hepatocellular carcinoma(HCC) in mice. Methods Mice that were transplanted with H22 ascites HCC were randomized into seven groups, which were intraperitoneally injected with blank microspheres, normal saline, three different doses of microspheres (9,18,and 36 mg/kg EPI), FEPI (9 mg/kg), and the combination (microspheres with EPI 4.5 mg/kg + FEPI 4.5 mg/kg). The survival time of all animals was recorded. he rates of increase in life span of all the treatment groups were calculated. Results EPI-PLA-MS significantly prolonged the survival time of HCC mice in a dose-dependent manner, with a maximal tolerated dose (MTD) of 18 - 36 mg/kg. The combination group had the highest average survival time, median survival time, and rate of increase in life span, which were (40.0±16.9) days, 33.5 days, and 222.58%, respectively. Conclusion EPI-PLA-MS combined with FEPI is highly effective in treating HCC in mice when intraperitoneally injected.

ABSTRACT:Objective To explore the relationship between neuroretinal rim area (RA)/retinal nerve fiber layer(RNFL) thickness and differential light sensitivity (DLS) in visual field in primary open angle glaucoma (POAG). Methods Fifty-one eyes of 51 patients with POAG were examined with HRTⅡ, GDx VCC, and Octopus 101 for RA, RNFL thickness, and DLS. Their correlations were evaluated with linear and logarithmic regression models globally and for individual sectors. Results In all the considered patients, visual field DLS was significantly correlated with neuroretinal RA or RNFL thickness globally and in individual sectors. Logarithmic fits were significantly better than linear fits for the global data and in most sectors. In preperimetric glaucoma, such correlations were weak and linear (R2=0.01-0.26). However, in perimetric glaucoma, the correlations were much stronger and curvilinear model gave the better fit (R2=0.15-0.84). Neuroretinal RA and RNFL thickness were linearly correlated. Conclusion Neuroretinal RA, RNFL thickness, and DLS in visual field were well correlated in POAG.

ABSTRACT:Objective To investigate the delayed cardioprotection induced by remifentanil in intact rat ischemia-reperfusion (I/R) models. Methods Totally 42 adult male Wistar rats weighing 200-300 g were randomly divided into 7 groups (n=6 in each group)：In Group Ⅰ, rats were injected with normal saline via tail vein，performed with the regimen of 3×5-min intravenous (IV) infusion at a rate of 0.1 ml&#8226;kg-1&#8226;min-1 24 h before I/R；In Group Ⅱ, rats were treated according to the same experimental protocols as in GroupⅠ except receiving additional naloxone (0.1 mg/kg) 10 minutes before normal saline pretreatment; In Groups Ⅲ, Ⅳ, Ⅴ, and Ⅵ, rats were treated with remifentanil via tail vein，performed with the regime of 3×5-min IV infusion at a rate of 2 μg&#8226;kg-1&#8226;min-1 12 h, 24 h, 48 h, and 72 h before I/R; In Group Ⅶ, the rats were treated according to the same experimental protocols as in Group Ⅳ except that they received additional naloxone (0.1 mg/kg) 10 minutes before remifentanil pretreatment. Heart rate（HR），mean arterial pressure (MAP), and a lead Ⅱ electrocardiogram were continuously monitored during IR process. To determine plasma concentration of creatine kinase myocardial isoenzyme-MB (CK-MB), arterial blood samples were obtained immediately before ischemia，and at the end of ischemia and reperfusion. After a 120-min reperfusion, heart was removed for the measurement of myocardial infarct size. Infarct size（IS） was expressed as percentage of the area at risk. Results HR, MAP, and rate-pressure product were not significantly different at each time points among all groups (P>0.05). Compared with Group Ⅰ, plasma concentrations of CK-MB at the end of ischemia and reperfusion and myocardial infarct size were significantly lower in Groups Ⅳ and Ⅴ (P<0.05). Compared with Group Ⅳ, plasma concentrations of CK-MB at the end of ischemia and reperfusion were significantly higher and myocardial infarct size was significantly larger in Group Ⅶ (P<0.05). Conclusion Remifentanil preconditioning induces delayed cardioprotection in intact rat ischemia-reperfusion model, which may be triggered via opioid receptors.

ABSTRACT:Objective To investigate the prevalence of cervical cancer, breast cancer, and reproductive tract infection (RTI) among women living in a county of China, identify these women’s recognition about these three diseases and their attitude toward the screening, and evaluate the feasibility of the packaging screening program in rural areas in China. Methods In this cross-sectional study, women aged 30-59 living in Xiang- yuan County, Shanxi Province, were surveyed by questionnaires and screened with visual inspection of cervix, breast clinic examination, and combined clinical examination and laboratory tests for RTI. Results Totally 630 women underwent interviews and packaging screening. The prevalences of cervical precancerous lesion, breast benign disease, and RTI were 0.2%, 14.0%, and 53.2%, respectively. No cancer case was found. The percentages of women knowing cervical cancer, breast cancer, and RTI as common diseases in women were 70.5%, 63.5%, and 52.9% after health education. Up to 92.5% of women preferred packaging screening to screening for single disease; however, they were not willing to pay the screening at current high cost. Conclusion sThe prevalences of breast benign disease and RTI are relatively high among women in rual areas in China. The women’s recognition about these three diseases is moderately good. The packaging screening program is well accepted and feasible in rural areas.

ABSTRACT:Objective To evaluate the role of multislice spiral computed tomography (MSCT) reconstruction technique in evaluation of living kidney donors. Methods From January 2006 to January 2009, six living kidney donors (3 men and 3 women, mean age 50.1 years) in Peking Union Medical Hospital underwent preoperative MSCT scanning to observe renal parenchyma, renal vessels, and collecting system. The 64-slice spiral CT scan technology was used for reconstruction of renal vascular and collection system, with maximum intensity projection (MIP), curved planar reformation (CPR), and volume rendering (VR). Surgical data of the 6 cases were followed up and the results of surgery served as controls. Results Seven renal arteries, including 1 right accessory artery, appeared at MSCT. Six renal veins, renal pelvis, and ureters were observed. All of their left kidneys were surgically resected and successfully transplanted into recipients. The operational findings were consistent with MSCT findings, with the accuracy of 100%. Conclusion sMSCT is an important technique for the comprehensive evaluation of living kidney donors. The technique deserves to be further applied.

ABSTRACT:Objective To evaluate the efficacy and safety of thrombolytic therapy with urokinase after systemic-pulmonary shunt. Methods Six patients who had thrombosis after systemic-pulmonary shunt were enrolled in this study. At the background of administration of the heparin at a dose of 0.2-0.3 U&#8226;kg-1&#8226;min-1, urokinase was intravenously administered with a loading dose of 15-20 U&#8226;kg-1&#8226;min-1 and a locked time period of 30 minutes, and then the dose was incessantly decreased to 4-10 U&#8226;kg-1&#8226;min-1. In addition to echocardiography (ECG), arterial partial pressure of oxygen/ inspired oxygen fraction (PaO2/FiO2),fibrinogen,activated partial thromboplastin time, and prothrombin time were determined to assess the clinical efficacy and side effects. Results The thrombolytic therapy with urokinase showed clinical effectiveness within 1 or 2 hours in all 6 patients. Efficiency of this therapy reached 100% during 12 to 24 hours. In 5 patients, the PaO2/FiO2 were over 50% higher than the early postoperative values. One patient received a second operation due to the excessively increased pulmonary blood flow. In 2 patients, pleural and mediastinal drainages increased when the thrombolytic therapy with urokinase began; however, they decreased after the urokinase dosages were adjusted. Conclusion It is feasible to use the thrombolytic therapy with proper dosage of urokinase after systemic-pulmonary shunt.

ABSTRACT:Elderly patients with acute myeloid leukemia (AML) tolerate intensive chemotherapy poorly and usually have poor prognosis. For elderly patients in good physical condition and without severe dysfunction of major organs, standard intensive induction chemotherapy is superior to non-intensive treatment or best supportive care alone. However, low-dose chemotherapy as post-remission treatment has more advantages than intensive chemotherapy. Intensive chemotherapy is not suitable for patients with unfavorable karyotypes, and genetic analysis is needed for individualized therapy regimen. Gemtuzumab ozogamicin may improve the survival of elderly patients who are intolerant to standard chemotherapy. Some patients may benefit from the transplantation of allogeneic stem cells after reduced-intensity conditioning.

ABSTRACT:Castleman’s disease (CD) is a rare lymphoproliferative disorder. The etiology of CD may involve viral infection，abnormal modulation of cytokines, and angiogenesis. Human herpes virus (HHV)-8 infection and interleukin-6(IL-6) overexpression may play key roles in the development of CD. Treatment options include surgical excision，radiation therapy, chemotherapy, antiviral therapy, and targeted therapy. No standardized treatment has been established for multicentric CD and the treatment efficacy usually is poor. Among newly available agents, the effectiveness of antiviral therapy against HHV-8 is unclear; anti-CD20 and anti-IL-6 receptor monoclonal antibodies have shown promising efficacy; thalidomide and bortezomib have shown their initial efficacy.

ABSTRACT:Aspirin is an important antithrombotic agent. However, its clinical benefit is impaired by aspirin resistance. The term of “aspirin resistance” usually refers to laboratory resistance. It can be identified by measuring thromboxane A2 or thromboxane-dependent platelet function. Clinical trials have shown that laboratory aspirin resistance is correlated with vascular events.

ABSTRACT:Idiopathic myelofibros is a Philadelphia-negative chronic myeloproliferative disorder. Potentially curative therapies, such as stem-cell transplantation, are reserved only for a minority of patients. Currently palliative therapies such as androgen and hydroxycarbamide are commonly used but with poor results. Thalidomide has anti-angiogenic effect and also can inhibit cytokines, and therefore plays a certain role in the treatment of a subset of idiopathic myelofibros.

ABSTRACT:Paraneoplastic pemphigus (PNP) is an autoimmune blistering skin disease associated with neoplasmas. Clinically, it is characterized by severe mucosal erosions and various cutaneous lesions. Suprabasal acantholysis and cleft with scattered necrotic keratinocytes are the unique histopathological features of PNP. The pathogenic autoantibodies existed in PNP sera, and their production was correlated with the associated tumor. Early detection and resection of the tumor are essential for the treatment of the disease.