Prospective evaluation of heparin-induced thrombocytopenia expert probability and 4T scores in Chinese patients with suspected heparin-induced thrombocytopenia / 中华医学杂志(英文版)

BACKGROUND@#Diagnosis of heparin-induced thrombocytopenia (HIT) is challenging. This study aimed to compare the diagnostic performance of HIT expert probability (HEP) and 4T scores, and to evaluate the inter-observer reliability for the 4T score in a clinical setting.@*METHODS@#This prospective study included HIT-suspected patients between 2016 and 2018. Three hematologists assessed the HEP and 4T scores. Correlations between scores and anti-platelet factor 4 (anti-PF4)/heparin antibodies were evaluated. Receiver operating characteristic curves and area under the curve (AUC) were used to assess the predictive accuracy of these two scoring models. The intraclass correlation coefficient (ICC) was used to assess the inter-observer agreement of 4T scores between residents and hematologists.@*RESULTS@#Of the 89 subjects included, 22 (24.7%) were positive for anti-PF4/heparin antibody. The correlations between antibody titer and either HEP or 4T scores were similar (r = 0.392, P < 0.01 for the HEP score; r = 0.444, P < 0.01 for the 4T score). No significant difference in the diagnostic performance was displayed between these two scores (AUC for the HEP score: 0.778 vs. AUC for the 4T score: 0.741, P = 0.357). Only 72 4T scores were collected from the residents, with a surprisingly low percentage of observers (43.1%) presenting the four individual item scores which made up their 4T score. The AUC of 4T score assessed by residents and hematologists was 0.657 (95% confidence interval [CI]: 536-0.765) and 0.780 (95% CI: 0.667-0.869, P < 0.05), respectively. The ICC of 4T score between residents and hematologists was 0.49 (95% CI: 0.29-0.65, P < 0.01), demonstrating a fair inter-observer agreement.@*CONCLUSIONS@#The HEP score does not display a better performance for predicting HIT than the 4T score. With the unsatisfactory completion rate, the inter-observer agreement of 4T score in a tertiary hospital is fair, underscoring the necessity for continuing education for physicians.

Prospective evaluation of heparin-induced thrombocytopenia expert probability and 4T scores in Chinese patients with suspected heparin-induced thrombocytopenia / 中华医学杂志(英文版)

Background@#Diagnosis of heparin-induced thrombocytopenia (HIT) is challenging. This study aimed to compare the diagnostic performance of HIT expert probability (HEP) and 4T scores, and to evaluate the inter-observer reliability for the 4T score in a clinical setting.@*Methods@#This prospective study included HIT-suspected patients between 2016 and 2018. Three hematologists assessed the HEP and 4T scores. Correlations between scores and anti-platelet factor 4 (anti-PF4)/heparin antibodies were evaluated. Receiver operating characteristic curves and area under the curve (AUC) were used to assess the predictive accuracy of these two scoring models. The intraclass correlation coefficient (ICC) was used to assess the inter-observer agreement of 4T scores between residents and hematologists.@*Results@#Of the 89 subjects included, 22 (24.7%) were positive for anti-PF4/heparin antibody. The correlations between antibody titer and either HEP or 4T scores were similar (r = 0.392, P < 0.01 for the HEP score; r = 0.444, P < 0.01 for the 4T score). No significant difference in the diagnostic performance was displayed between these two scores (AUC for the HEP score: 0.778 vs. AUC for the 4T score: 0.741, P = 0.357). Only 72 4T scores were collected from the residents, with a surprisingly low percentage of observers (43.1%) presenting the four individual item scores which made up their 4T score. The AUC of 4T score assessed by residents and hematologists was 0.657 (95% confidence interval [CI]: 536–0.765) and 0.780 (95% CI: 0.667–0.869, P < 0.05), respectively. The ICC of 4T score between residents and hematologists was 0.49 (95% CI: 0.29–0.65, P < 0.01), demonstrating a fair inter-observer agreement.@*Conclusions@#The HEP score does not display a better performance for predicting HIT than the 4T score. With the unsatisfactory completion rate, the inter-observer agreement of 4T score in a tertiary hospital is fair, underscoring the necessity for continuing education for physicians.

Advances of Coagulation Factor XIII / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To provide a comprehensive literature review on roles of coagulation factor XIII (FXIII) in coagulation, wound healing, neoplasm, bone metabolism, and pregnancy.</p><p><b>DATA SOURCES</b>All articles in PubMed with key words "Coagulation factor XIII", "wound", "leukemia", "tumor", "bone," and "pregnancy" with published date from 2001 to 2016 were included in the study. Frequently cited publications before 2000 were also included.</p><p><b>STUDY SELECTION</b>We reviewed the role of FXIII in biologic processes as documented in clinical, animal, and in vitro studies.</p><p><b>RESULTS</b>FXIII, a member of the transglutaminase (TG) family, plays key roles in various biological processes. Besides its well-known function in coagulation, the cross-linking of small molecules catalyzed by FXIII has been found in studies to help promote wound healing, improve bone metabolism, and prevent miscarriages. The study has also shown that FXIII concentration level differs in the blood of patients with leukemia and solid tumors and offers promises as a diagnostic indicator.</p><p><b>CONCLUSIONS</b>FXIII has many more biologic functions besides being known as coagulation factor. The TG activity of FXIII contributes to several processes, including wound healing, bone extracellular matrix stabilization, and the interaction between embryo and decidua of uterus. Further research is needed to elucidate the link between FXIII and leukemia and solid tumors.</p>

Clinical Features of Patients with Castleman's Disease Complicated Systemic Lupus Erythematosus / 中国医学科学院学报

Objective To investigate the clinical features of patients with Castleman's disease (CD) and systemic lupus erythematosus (SLE). Methods According to the diagnostic information between 1994 to 2014 extracted from the database of the Medical Record Department of Peking Union Medical College Hospital (PUMCH),patients with CD and SLE were included. A thorough literature review utilizing the key words of "Castleman's disease","systemic lupus erythematosus","SLE",and "lupus" was performed in PubMed during the same period. Cases with detailed clinical information were included while cases without detailed information were excluded from the analysis of this study. Results Nine patients worldwide were available for analysis [2 cases from PUMCH,accounted for 0.03%(2/6502) of all patients diagnosed as SLE and 1.0% (2/100) of patients diagnosed as CD during the same period] with a male-to-female ratio of2:7. The median age at diagnosis of CD was 39.0 years (range:21- 60 years). All patients were diagnosed as multicentric CD with generalized peripheral lymphadenopathy. Pathologic examination showed a balanced distribution:plasma cell variant:hyaline-vascular variant:mixed variant=3:3:3. Fever was the most common symptom (88.9%,8/9). Blood system was the most commonly involved system (88.9%,8/9) and kidneys were the most commonly involved organ (88.9%,8/9). Autoimmune thrombocytopenia (AITP) was observed in 55.6% (5/9) of patients,which was significantly higher than the general SLE patients (15.0%) (P<0.01). None of the 9 patients had evidence of central nervous system involvement. Conclusions CD complicated by SLE is a rare clinical condition. Compared to the general SLE population,this subgroup of patients may have higher rate of AITP and lower rate of central nervous system involvement.

Risk factors and precautions of inpatient suicide from the perspective of nurses: A qualitative study / 华中科技大学学报（医学）（英德文版）

The risk factors and precautions of inpatient suicide were explored. Thirty suicide victims were drawn from the adverse event reports of suicidal act during hospitalization in a general hospital from 2008 to 2014. Data were gathered from the focus group interviews of twelve nurses who had experienced inpatient suicide. The data were analyzed by using analytical technique based on grounded theory, and software QSR NVIVO8 was used to aid the collation of data. Three main themes of risk factors about inpatient suicide emerged from the analysis: individual value, social factors and environmental factors. The individual value was categorized into different groups such as sense of guilt, hopelessness and low self-esteem. Social factors included two aspects of negative life events and social support. Three themes of precautions about inpatient suicide appeared in this study: evaluation, nursing and information exchange. Evaluation was elaborated from both physical and psychological assessments. This finding extends existing work of risk factors and precautions about inpatient suicide and brings new knowledge about the reasons why inpatients commit suicide.

Risk factors and precautions of inpatient suicide from the perspective of nurses: A qualitative study / 华中科技大学学报（医学）（英德文版）

The risk factors and precautions of inpatient suicide were explored. Thirty suicide victims were drawn from the adverse event reports of suicidal act during hospitalization in a general hospital from 2008 to 2014. Data were gathered from the focus group interviews of twelve nurses who had experienced inpatient suicide. The data were analyzed by using analytical technique based on grounded theory, and software QSR NVIVO8 was used to aid the collation of data. Three main themes of risk factors about inpatient suicide emerged from the analysis: individual value, social factors and environmental factors. The individual value was categorized into different groups such as sense of guilt, hopelessness and low self-esteem. Social factors included two aspects of negative life events and social support. Three themes of precautions about inpatient suicide appeared in this study: evaluation, nursing and information exchange. Evaluation was elaborated from both physical and psychological assessments. This finding extends existing work of risk factors and precautions about inpatient suicide and brings new knowledge about the reasons why inpatients commit suicide.

Prevalence and features of pathogenic bacteria in the department of hematology without bone marrow transplantation in Peking Union Medical College Hospital from 2010 to 2012 / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the incidence, pathogens, and clinical features of infection in consecutive cases from 2010 to 2012 in Peking Union Medical College Hospital.</p><p><b>METHOD</b>The incidence, pathogen, treatment, and outcomes of patients with hematological diseases who had positive findings of bacterium in their samples from 2010 to 2012 were retrospectively analyzed.</p><p><b>RESULTS</b>There were 449 positive samples (5.8%) from 4 890 patients during this period, among which 388 were proved to be with pathogenic bacteria. Samples separated from patients with community-aquired infections accounted for 8.4% of all positive samples. Most community-aquired infections were caused by Gram-negative bacteria (75%), although no multidrug-resistant bacteria was observed. Samples separated from patients with nosocomial infections accounted for 91.6% of all positive samples. Respiratory tract (49.4%) and peripheral blood (32.6%) were the most common samples with positive results. Skin soft tissues (10.4%), and urine (3.7%) were less common samples. Most of the pathogenic bacteria of the nosocomial infections were Gram-negative (66.9%). The most common Gram-negative bacteria included Escherichia coli (13.8%), Pseudomonas aeruginosa (12.1%), and Klebsiella pneumonia (12.1%), while Staphylococcus aureus (10.4%), Enterococcus faecium (7.0%), and Staphylococcus epidermidis (5.1%) were the most common Gram-positive bacteria. Gram-negative bacteria consisted of most of sputum samples and peripheral blood samples. Samples from the surface of skin wound and anal swab were composed largely by Gram-positive bacteria (63.8%). The detection rates of extended-spectrum beta-lactamase-producing Klebsiella pneumonia/Klebsiella oxytoca, Escherichia coli, and Proteus mirabilis were 24.0%, 87.9% and 38.4%, respectively. The resistance to Acinetobacter baumannii was serious. Multidrug-resistant, extensive drug resistant and pan drug resistant A. baumannii acountted for 74% of all A. Baumannii infections. Stenotrophomonas maltophilia showed low resistance to sulfamethoxazole/trimethoprim, levofloxacin and minocycline. Also, 22 methicillin-resistant Staphylococcus aureus and 9 methicillin-resistant Staphylococcus Epidermidis were detected, which were only sensitive to vancomycin, teicoplanin, and linezolid. All patients were treated in the haematology wards and most of them were under agranulocytosis or immunosuppression. Finally, 22 patients reached clinical recovery through anti-infective therapy, whereas 49 patients died. Among those deaths, 42 patients attributed to severe infections and infection-associated complications. Fourteen of all the deaths might be infected with drug-resistance bacteria. There were 61 samples proved to be bacteria colonization. Nonfermenters such as Acinetobacter baumannii and Stenotrophomonas maltophilia made up for a large amount of bacteria colonization.</p><p><b>CONCLUSIONS</b>The pathogens of nosocomial infections in the hematology ward are mainly Gram-negative bacteria. The incidences and pathogens vary from different infection sites. Nosocomial infection still has a higher mortality rate. Once nonfermenters are detected positive, the pathogenic or colonial bacteria should be distinguished.</p>

Exploring the pathogenesis and therapy of liver cancer from "damp-heat insidious pathogen" to "cancer toxin" / 中国中西医结合杂志

From a macro-level analysis of the attributes and pathogenic features of HBV, the main pathogenic factor for chronic liver diseases including viral hepatitis, cirrhosis, and liver cancer, the concept of damp-heat insidious pathogen was obtained, according to which, in-depth discussions were undertaken. Adopting syndrome typing of Wei (defense), qi (vital energy), Ying (nutrients), and blood, the pathogens leading to different syndromes as well as new products such as pathological "sputum", "stasis" in the disease process were understood, and then, the pathological "sputum" and "stasis", as the hub, playing a role in chronic lesions of the liver collateral were explained. Finally the pathological "sputum" and "stasis" blend and form cancer toxin. Through a comprehensive understanding of the development of chronic liver diseases, it is clear that damp-heat insidious pathogen, as its initiating factor, always exists in the whole process. We summed up heat clearing, dampness resolving, and detoxification was the principle for treating chronic liver disease.

Aitongxiao recipe regulated survivin and Bcl- 2 in rats' transplanted hepatoma carcinoma cell / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the main mechanisms of Aitongxiao Recipe (ATXR) for anti-tumor at the molecular level, and to clarify different efficient drugs' roles in anti-tumor, thus in-depth explaining the objectivity and substance of "cancer toxic" theory.</p><p><b>METHODS</b>Walker-256 tumor strain was used for Wistar rat transplanted liver cancer modeling. After successful modeling rats were randomly divided into 5 groups, i. e., the ATXP group, the qi regulating and blood circulating group (as the assembled I group), the heat clearing and detoxification group (as the assembled II group), the body resistance strengthening and cultivating group (as the assembled III group), and the model group, 10 in each group. Corresponding medication was given to rats in each group for 14 successive days. Finally rats were sacrificed and the tumor mass was taken out. The apoptosis rate and the cell cycle of tumor cells were detected by flow cytometry Annexin V/PI. The protein and mRNA expressions of Bcl-2 and survivin were detected using immunohistochemistry and real-time fluorescent quantitative PCR.</p><p><b>RESULTS</b>(1) The apoptosis of hepatoma carcinoma cells could be obviously promoted in the ATXP group. The cell cycle could also be affected, making major cells arrest at G0/G1 phase. The proliferation of hepatoma carcinoma cells was effectively prevented. The efficacy in the assembled II group was in line with that in the ATXP group with no statistical difference (P>0.05). It was also effective in the assembled III group, but its efficacy was not as good as that in the former two groups, showing statistical difference (P<0.01). (2) ATXP could obviously down-regulate the protein and mRNA expressions of Bcl-2 and survivin in hepatoma carcinoma cells. Drugs for heat clearing and detoxification showed significant effects on down-regulating the protein and mRNA expressions of Bcl-2 and survivin in hepatoma carcinoma cells. Their effects were similar to that of ATXP (P>0.05). The effects of drugs for body resistance strengthening and cultivating were not as good as the former two, showing statistical difference (P<0.01). Drugs for blood circulating and stasis removing could up-regulate the protein and mRNA expressions of Bcl-2 and survivin to some extent.</p><p><b>CONCLUSIONS</b>(1) ATXP could increase the apoptosis ratio of hepatoma carcinoma cells obviously through down-regulating the protein and mRNA expressions of Bcl-2 and survivin, thus inhibiting their proliferation. (2) Drugs for heat clearing and detoxification played the most important roles in ATXP. The evil heat and dampness (damp-heat insidious pathogen) is the most fundamental carcinogenic factors. The insufficiency of vital qi is also one of the pathogenic factors. The mechanisms of phlegm, stasis, and other pathological products are not clear and await further studies.</p>

Recombinant activated factor VII in hemophagocytic lymphohistiocytosis with disseminated intravascular coagulation / 中华医学杂志(英文版)

Hemophagocytic lymphohistiocytosis (HLH) is a lifethreatening disorder due to hyperinflammation resulting in infiltration of different organs with extensive hemophagocytosis. Severe coagulopathy was one of the main reasons for death in HLH. Over secretion of plasminogen activator by activated macrophages leads to hyperfibrinolysis. We reported a 36-year-old woman who was diagnosed as HLH probably secondary to lymphoma. Massive bleeding from gut and retroperitoneal area were not able to be controlled by conventional hemostatic treatments. This patient received one dose recombinant activated factor VII (rFVIIa) 3.6 mg (70 μg/kg). Hemostatic effect was achieved in 0.5 hour and lasted 24 hours. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were quickly corrected to normal ranges. Fibrinogen level elevated from 0.5 g/L before using rFVIIa to 1.8 g/L 20 hours after. Although dexamethasone and etopside were administrated to treat HLH, this patient died from septic shock after persistent neutropenia. This suggests that rFVIIa may be effective in the management of intractable hemorrhage in patients with HLH.

Porcine anti-human lymphocyte globulin plus cyclosporine A therapy for severe aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of porcine anti-human lymphocyte globulin (P-ALG) plus cyclosporine A (CsA) therapy for severe aplastic anemia (SAA).</p><p><b>METHODS</b>Forty-eight SAA patients (31 males, 17 females) including 17 very severe aplastic anemias (vSAA) were treated with ALG plus CsA between 1999 to 2009 in our hospital and the outcomes were analyzed retrospectively for early mortality, response rate and quality, survival rate, toxicity and complications.</p><p><b>RESULTS</b>The median age was 28 (13 - 64) years. The interval from diagnosis to treatment was 45 days. The median neutrophil count at diagnosis was 0.178 × 10(9)/L. Overall response was 83.3% (54.2% complete, 29.2% partial) with a median time of 90 (23 - 380) days. 10.4% died of infection within 30 days mainly of fungi infection. Only 1 patient relapsed 2 years after treatment. No clonal disease was found. The 1.5-year survival rate was 87.5%. vSAAs had less response, higher early mortality and less survival (64.7%, 29.4% and 51.8%, respectively) compared to that of SAA (93.5%, 0, 100%, respectively, P < 0.05). Grouped patients with different age, gender, intervals between diagnosis and treatment and pre-existing infections had similar response. The main side effects were fever and skin rash (52.1%), serum sickness (16.7%), impaired liver function (60.4%) and hemorrhage (2.1%). No treatment-related mortality was found.</p><p><b>CONCLUSION</b>P-ALG plus CsA is an ideal and well tolerated treatment for SAA but not for vSAA.</p>

Anti-glioma effect of combination of bFGF-siRNA and Vpr in nude mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the anti-glioma effect of recombinant adenovirus mediated combined gene therapy of bFGF-siRNA and HIV1-Vpr in vivo.</p><p><b>METHODS</b>Mouse glioma model was established by injecting 5 × 10(6) LN229 cells into BALB/c-nu nude mice. 30 nude mice were randomly divided into 5 groups: the negative control group, mock group, bFGF-siRNA group, Vpr group and combined therapy group, which at regular intervals were injected with PBS, rAd5-null, rAd5-bFGF-siRNA, rAd5-Vpr, rAd5-bFGF-siRNA plus rAd5-Vpr, respectively. The tumor volume was recorded every third day to draw a growth curve. After four weeks treatment, the mice were killed and specimens were taken. HE, immunohistochemical and TUNEL staining were performed to observe the cell morphology, detect the changes of relevant target proteins and cell apoptosis, respectively. Also the ultrastructural changes were observed by electron microscopy.</p><p><b>RESULTS</b>The tumor growth inhibition rates were 36.9%, 37.2% and 58.6% in the bFGF-siRNA group, Vpr group and combined therapy group, respectively, and the combined therapy group showed the most significant effect (P < 0.05). Also the results of HE, immunohistochemical and TUNEL staining revealed that the combined therapy group had the best effects on proliferation inhibition and apoptosis induced in glioma cells (P < 0.05). The most significant ultrastructural changes were observed in the combined therapy group.</p><p><b>CONCLUSION</b>The combined gene therapy of bFGF-siRNA with Vpr shows a prominent and synergistic anti-glioma effect compared with that of mono-gene therapy in nude mice.</p>

Value of reticulated platelet counts in identifying thrombocytopenia aetiology / 中国实验血液学杂志

This study was to evaluate the role of reticulated platelets (RP) assay in the distinguishing the different causes of thrombocytopenia. The RP and immature platelet fraction (IPF) were stained by a nucleic acid-specific dye oxazine, and assayed by XE-2100 blood cell counter with an upgraded software in the reticulocyte/optical platelet channel. RP and IPF were measured in 137 thrombocytopenic patients and 187 normal controls. The results showed that the mean IPF was 1.07% in normal controls, and 10.28% in 109 patients with immune thrombocytopenia (p<0.01), RP absolute value in ITP group was higher than that in control group, there was significant difference between them (p=0.036). The mean IPF was 10.47% in patients with primary immune thrombocytopenia (PITP), and 9.45% in patients with secondary ITP (SITP). There was no significant difference of IPF between PITP and SITP group (p=0.635), but IPF in these 2 groups both were significantly higher than the normal controls. The mean IPF in 28 thrombocytopenic patients with hypocellular marrow was 2.37%. There was no difference of IPF between thrombocytopenic patients with hypocellular marrow and the normal controls (p=0.252), but the absolute counts of RP in the former was significantly lower than in the latter (p<0.05). The IPF cut-off for a diagnosis of thrombocytopenia with hypercellular marrow was 2.45%, the sensitivity was 92.7% and specificity 94.1%. It is concluded that the whole-blood IPF measurement by XE-2100 blood cell counter is an useful screening test to differentiate patients with thrombocytopenia of different causes. An IPF above 2.45% has both a high sensitivity and specificity for a diagnosis of thrombocytopenia with a hypercellular marrow.

Effect of arsenic pentaoxide on proliferation and apoptosis of human umbilical vein endothelial cell / 中国医学科学院学报

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>As2O5 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.</p>

Comparison of modified Bethesda assay and Nijmegen assay in detecting FVII inhibitor in patients with hemophilia A / 中国医学科学院学报

<p><b>OBJECTIVE</b>To compare the sensitivity and practicability of modified Bethesda assay and Nijmegen assay in detecting factor VIII (FVIII) inhibitor.</p><p><b>METHODS</b>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 > or = 0.6 BU/ml.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>Modified standard Bethesda assay is a convenient and feasible method for detecting FVIII inhibitors.</p>

Comparison of efficacy and adverse effects between arsenic trioxide and all-trans retinoic acid in patients with acute promyelocytic leukemia / 中国医学科学院学报

<p><b>OBJECTIVE</b>To compare the efficacy and adverse effects between arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>Both 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.</p>

Prognostic differences among different age limits in Chinese elderly patients with non-Hodgkin's lymphoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the feasible age limits in Chinese elderly patients with non-Hodgkin's lymphoma (NHL).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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 > or = 75 years. The OS rate was significantly different between patients aged > or = 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.</p><p><b>CONCLUSION</b>Sixty-five years can be regarded as the age limit in Chinese NHL patients.</p>

Blood concentration monitoring during high-dose methotrexate treatment / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the clinical value of blood concentration monitoring during high-dose methotrexate (MTX) treatment.</p><p><b>METHODS</b>High-dose MTX (1.5-9.0 g) 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 0.1 micromol/L.</p><p><b>RESULTS</b>Forty-four hours after the start of administration, the blood MTX concentration (C(MTX/44h)) was > or = 5 micromol/L in 6 patients (2.8%) and was between 1 and 5 micromol/L in 23 patients (10.6%). C(MTX/44h) > or = 1 micromol/L was more common in patients received 5.0 g MTX. No severe adverse event was observed in all patients.</p><p><b>CONCLUSIONS</b>Blood 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 5.0 g MTX. Application of high-dose MTX therapy under the monitoring of blood MTX concentration is safe and feasible.</p>

Clinical features and prognosis in 49 patients with Castleman's disease / 中国医学科学院学报

<p><b>OBJECTIVE</b>To analyze the clinical features and prognosis of patients with Castleman's disease (CD).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>In patients with uni-centric 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.</p><p><b>CONCLUSIONS</b>The 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.</p>

Clinical features of invasive pulmonary fungal infection secondary to malignant blood diseases / 中国医学科学院学报

<p><b>OBJECTIVE</b>To summarize the clinical features of invasive pulmonary fungal infection (IPFI) secondary to malignant blood diseases (MBD).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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 fluconazole or itraconazole as the first-line therapy had to switch to other medicines because of poor infection control.</p><p><b>CONCLUSIONS</b>IPFI secondary to MBD is most common in AML patients. Patients with NR of AML, neutropenia or agranulocytosis, and long-term broad-spectrum antibiotics usage are susceptible to IPFI. Fluconazole and itraconazole have low efficacy, and other more potent anti-fungal medicines should be considered.</p>