Palladium/XuPhos-catalyzed enantioselective cascade Heck/intermolecular C(sp2)-H alkylation reaction.

Palladium-catalyzed enantioselective domino Heck/intramolecular C-H functionalization reaction, as a valuable strategy for creating molecular diversity, has remained a prominent challenge. Here, we describe a Pd/XuPhos catalyst for asymmetric domino Heck/intermolecular C-H alkylation of unactivated alkenes with diverse polyfluoro- and heteroarenes in a highly chemo- and enantioselective manner. This process enables efficient synthesis of various dihydrobenzofurans, indolines and indanes, which are of interest in pharmaceutical research and other areas. Late-stage modifications of the core structures of natural products are also well showcased. Moreover, synthetic transformations create a valuable platform for preparing a series of functionalized molecules. Several control experiments for mechanistic study are conducted to pursue a further understanding of the reaction.

Influence factors and predictive ability of a risk prediction model for carotid atherosclerosis in a follow-up population / 中华疾病控制杂志

Objective To explore factors influencing the incidence of carotid atherosclerosis in different genders so as to provide reference for the specific prevention of the disease. Methods A nested case-control study was conducted to analyze factors influencing the incidence of carotid atherosclerosis in Jinchang cohort population who were randomly selected through stratified sampling by age and followed up. A risk prediction model was established and the goodness of fit was evaluated by the area under the receiver operator characteristic curve (ROC). Results The standardized incidence of carotid atherosclerosis in this follow-up population was 12.32%, and the incidence rate of males (13.65%) was greater than that of females (11.29%). The difference was statistically significant ( 2=4.267, P<0.001). Age, education, elevated systolic blood pressure, and elevated low-density lipoprotein cholesterol were common risk factors for carotid atherosclerosis in both men and women. Elevated fasting plasma glucose (OR=2.556, 95% CI: 1.618-4.038) and elevated triglyceride (OR=1.535, 95% CI: 1.058-2.227) were only associated with men. Abdominal obesity (OR=1.414, 95% CI: 1.013-1.974) was only associated with women. The area under ROC of male and female prediction models was 0.835 (95% CI: 0.815-0.856) and 0.809 (95% CI: 0.788-0.831), respectively. The sensitivity was 78.0% and 78.9%, the specificity was 78.8% and 73.1%, and the diagnostic coincidence rate was 91.3% and 82.4%, respectively. Conclusions There are different risk factors for carotid atherosclerosis in males and females, and targeted prevention and control measures should be taken according to gender. The risk prediction model established by Logistic regression had certain guiding value.

A Clinical Experience of Laparoscopic Nephrectomy in Primary Hospital / 昆明医科大学学报

Objective To investigate the clinical value and the experience of retroperitoneal laparoscopic nephrectomy in primary hospitals. Methods A retrospective analysis of 20 cases of retroperitoneal nephrectomy performed in the people's hospital of Jianshui from July 2014 to December 2017 and 23 cases of open nephrectomy in the same period as the control group, the two groups of surgery and postoperative recovery were analyzed and compared. Results The two groups of patients were operated successfully. The surgery time of the laparoscopic group was (110.14 ±15.63) min and the control group was (100.33 ±10.58) min. There was no statistical difference between the two groups (P＞0.05). No complications occurred during the follow-up period between the two groups, and the difference was not statistically significant. The intraoperative blood loss in the two groups was (40.63 ±22.21) ml and (80.45 ±38.31) m L respectively, and the difference was statistically significant (P＜ 0.05).The indwelling time of drainage tube in the two groups was (2-3) days and (6-7) days respectively. The difference was statistically significant (P＜ 0.05), and the hospitalization time was (3.2 ±2.2) days and (6.4 ± 3.3) days respectively, the difference was statistically significant (P＜0.05). Conclusions Laparoscopic nephrectomy has the advantages of less trauma, faster recovery and shorter hospital stay. With the improvement of operation technique, it will bring more advantages and be worth popularizing.

Heavy Metal Assessment among Chinese Nonferrous Metal-exposed Workers from the Jinchang Cohort Study / 生物医学与环境科学（英文）

Environmental exposure to heavy metals has been linked to a wide range of human health hazards. We detected the levels of 15 metals in urine samples from 500 representative sub-samples in an ongoing occupational cohort study (Jinchang Cohort) to directly evaluate metal exposure levels. Fifteen metals, namely As, Ba, Be, Cd, Cs, Cr, Co, Cu, Pb, Mn, Ni, Se, Tl, U, and Zn, were detected by inductively coupled plasma quadruple mass spectrometry. The results showed that median creatinine adjustment and geometric mean urinary metal levels were higher in the heavy metal-exposed group, except Se and Zn, than other reported general or occupational populations. Further studies should address the effects of heavy metals on human health.

Anatomical double bundle reconstruction of medial patellofemoral ligament with allograft tendon in the treatment of patellar dislocations / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the clinical therapeutic results of allograft tendon for anatomical reconstruction of medial patellofemoral ligament (MPFL) for the treatment of patellar dislocations.</p><p><b>METHODS</b>From September 2008 to June 2013, 16 patients with patellar dislocation underwent MPFL reconstructions. There were 2 males and 14 females, aged 11 to 27 years old (16 years old on average). Patellar dislocations occurred in 11 left and 5 right knees. The disease course ranged from 3 to 10 years. The frequency of dislocation ranged from 9 to 33 times (19 times on average). Affected knee joints showed patellar instability; the range of action for patella obviously increased. The X-ray films showed patellar dislocation. The preoperative Q angle was (36 ± 9)°, and the congruence angle was (63 ± 18)°. Reconstruction was performed via allograft tendon. Allograft tendon was fixed through the superomedial pole of the patella, and the other end was fixed at the natural MPFL insertion site near the medial femoral condyle with an interference screw in a bone tunnel. All the patients were evaluated postoperatively; Kujala patellofemoral scores, objective knee function, complications, and reoperations were assessed.</p><p><b>RESULTS</b>Primary healing was achieved in all cases. No infection or necrosis and absorption of grafts was observed. All the patients were followed up for an average of 16.4 months (ranged, 10 to 24 months) postoperatively. At the latest follow-up, all the patients had no pain, swelling and patellar instability; neither patella redislocation nor fracture occurred. The X-ray films showed good position of tunnel 6 months after operation, and the congruence angle was (5 ± 9)°, showing statistically significant difference when compared with preoperation (P < 0.05). The postoperative Q angle was (17 ± 8)°, the Kujala knee function score improved significantly from 45.20 ± 9.20 to 89.30 ± 6.40 at the latest follow-up, showing statistically significant difference (P < 0.05).</p><p><b>CONCLUSION</b>MPFL reconstruction improves clinical symptoms. Anatomical MPFL reconstruction is effective for patellar dislocation, and it offers good recovery of the premorbid patella mechanics. The interference screw provides firm fixation. Allograft can avoid the graft harvest site morbidity, but it increases the cost of the surgery.</p>

Dynamic Changes in DNA Damage and Repair Biomarkers with Employment Length among Nickel Smelting Workers / 生物医学与环境科学（英文）

Our study explored the dynamic changes in and the relationship between the DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the DNA repair marker 8-hydroxyguanine DNA glycosidase 1 (hOGG1) according to the length of occupational employment in nickel smelting workers. One hundred forty nickel-exposed smelting workers and 140 age-matched unexposed office workers were selected from the Jinchang cohort. The 8-OHdG levels in smelting workers was significantly higher than in office workers (Z=-8.688, P<0.05) and the 8-OHdG levels among nickel smelting workers in the 10-14 y employment length category was significantly higher than among all peers. The hOGG1 levels among smelting workers were significantly lower than those of non-exposed workers (Z=-8.948, P<0.05). There were significant differences between employment length and hOGG1 levels, with subjects employed in nickel smelting for 10-14 y showing the highest levels of hOGG1. Correlation analysis showed positive correlations between 8-OHdG and hOGG1 levels (r=0.413; P<0.01). DNA damage was increased with employment length among nickel smelting workers and was related to the inhibition of hOGG1 repair capacity.

Metal Exposure and Risk of Diabetes and Prediabetes among Chinese Occupational Workers / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study the association between metal exposure and risk of diabetes and prediabetes among Chinese workers exposed to metals.</p><p><b>METHODS</b>We used data obtained from the baseline survey of the Jinchang Cohort Study of workers in Jinchang Industry, the largest nickel production company in China. A total of 42,122 workers ⋝20 years of age were included in the study. A standardized, structured questionnaire was used to collect epidemiological information. Physical examinations and laboratory tests were conducted to evaluate the health status of the participants and to measure various biomarkers including blood sugar, lipids, and urinary metal concentrations. Logistic regression was used to study the association between occupational groups categorized according to the measured metal levels (office workers, low-level; mining/production workers, mid-level; and smelting/refining workers, high-level) and risk of diabetes and prediabetes.</p><p><b>RESULTS</b>The overall prevalence of diabetes and prediabetes was 7.5% and 16.8%, respectively. The adjusted odds ratios for diabetes among mining/production workers and smelting/refining workers compared to office workers were 1.5 (95% CI: 1.3, 1.7) and 3.8 (95% CI: 3.4, 4.3), respectively. No association was observed between these occupational groups and prediabetes in this study.</p><p><b>CONCLUSION</b>Occupations associated with higher levels of metal exposure were associated with an increased risk of diabetes in this cohort. More studies are needed to confirm this observed association.</p>

Value of bone marrow biopsy histopathological finding in diagnosing myelodysplastic syndrome / 重庆医学

Objective To evaluate the value of plastic-embedded bone marrow (BM ) biopsy sections in diagnosing myelodysplas-tic syndrome(MDS) .Methods HGF and Gomori stained .Glycol methacrylate(GMA) embedded BM biopsy specimens were detec-ted from 125 MDS patients with 25 cases in good health as control .Dyshematopoiesis and abnormal stroma cell responses were se-lected as main observed projects .Results Bone marrow biopsy sections gave an exact assessment of cellularity ,19 cases (15 .2% ) showed a decrease of cellularity as hypocellular MDS .66 cases(52 .8% ) of these cases did show abnormal localization of erythro-blastic clusters ,biopsy of 64(62% ) of low risk group 103 cases did show abnormal localization of immature precursors such as blasts and promyelocytes(ALIP positive) .Numeration of megakaryocytes and mast cells within 1mm2 acre of BM tissue were all much in MDS group than in control group .Gomori′s stain revealed moderate increase in reticulin fibres in 65 cases ,10 cases(8 .0% ) showed degree of myelofibrosis were + + + as hyperfibrotic MDS .Among 125 cases ,33 cases(26 .4% ) of bone marrow biopsies showed different types of erythrocytic and granulocytic immature cells with unusual intrasinusoidal bone marrow infiltration .Con-clusion It is clear that GMA embedded BM biopsy section is helpful in making diagnosis of MDS ,and has important clinical appli-cation value .

Nickel-exposed workers in China: a cohort study / 生物医学与环境科学（英文）

There are more than 50 000 workers in Jinchuan Group Co, Ltd (JNMC). Since all staff in JNMC are eligible for a medical examination every two years, only 23 484 nickel-exposed subjects who participated in medical examination were included in this study. Their data, collected from June 22, 2011 to September 28, 2012, in a comprehensive epidemiological survey and during medical examinations, permitted an extensive evaluation of the relation between metal exposure, gene, epigenetics and risk of human diseases. Their lifestyle investigation showed that the overall prevalence of current smokers, alcohol drinkers, and tea drinkers was 39.1%, 19.7%, and 55.2%, respectively. The prevalence of hypertension, allergic rhinitis and cholecystitis , the top 3 prevalent diseases, was 11.7%, 11.0%, and 8.9%, respectively.

Prevalence of metabolic syndrome in Chinese nickel-exposed workers / 生物医学与环境科学（英文）

The prevalence of metabolic syndrome (MS) was investigated in Chinese nickel-exposed workers. A total of 35 104 subjects were enrolled in this study. The age-adjusted prevalence of MS, BMI⋝25, diabetes, hypertension, and abnormal lipid was 13.9%, 29.5%, 12.8%, 27.5%, and 47.1%, respectively. The prevalence of BMI⋝25, hyperglycemia, and hypertension increased with the age of males and females, and was higher in males than in females (37.1% vs 21.5%, 15.9% vs 12.1%, 35.0% vs 24.3%, 54.3% vs 40.4%).

Stady on the clinical characteristics of 10 patients with idiopathic cytopenia of undetermined significance / 重庆医学

Objective To analyze the clinical and pathologic features in patients with ldiopathic cytopenia of undetermined signif-icance (ICUS) ,and provide the diagnostic basis .Methods 10 ICUS patients who did not fulfil minimal diagnostic criteria for MDS but suffered from constant (>6 months) progressive cytopenia ,with no marked dysplasia (<10% in three-major cell lineages) and abnormal karyotype were reported .Results 2 of 10 patients transited to MDS ,bone marrow review showed that ≥2 cells appeared diagnostic pathology development .Karyotype analysis showed that 1 case was still normal ,1 case lost a normal chromosome 20 (20q-) ,the rest 8 cases had been efollowed up for 6 to 25 months and still maintain ICUS .Conclusion Patients with MDS who fail to meet the diagnostic criteria of ICUS ,must carry out regular follow-up .There are some patients can transition to public MDS after a certain incubation period ,in fact it is Pre-MDS or MDS-early before ,which shows that ICUS should cause clinical attention ,so that avoid missed diagnosis .

Correlation between clinical outcome of 115 patients with idiopathic thrombocytopenic purpura and megakaryocyte counts in bone marrow biopsy / 中国实验血液学杂志

The aim of study was to explore the influence of the number of megakaryocytes in bone marrow smear and trephine biopsy on clinical outcome of idiopathic thrombocytopenic purpura (ITP). The clinical outcome of 115 patients with ITP was compared by different clinical subtype, number of blood platelet, number of megakaryocyte in bone marrow smear and trephine biopsy. The results showed that: (1) the clinical outcome of acute ITP was better than that of chronic ITP, the short clinical outcome of acute ITP and chronic ITP were 86.6% vs 60.4% respectively (p < 0.01), the long clinical outcome of them were 82.5% vs 68.9% respectively (p < 0.05); (2) different number of blood platelet at occurrence of diseases had no obviously influence on clinical outcome of patients with ITP; (3) all cases were subgrouped according to number of megakaryocyte in bone marrow smear, the number of megakaryocyte in bone marrow smear less than 7/4.5 cm(2) was defined as group I, the number of megakaryocyte between 7/4.5 cm(2) to 35/4.5 cm(2) was defined as group II, and the number of megakaryocyte in bone marrow smear greater than 35/4.5 cm(2) was defined as group III. The effective rates of 3 groups in short term treatment were 53.3%, 73.8% and 86.2% respectively, and there were statistical difference between these 3 groups (p < 0.01), the effective rates of these 3 groups in long term treatment were 42.8%, 84.6% and 85.5% respectively, and there was no statistical different between group II and group III (p > 0.05), but both had statistical difference, as compared with group I (p < 0.01). (4) all cases were subgrouped by the number of megakaryocyte in trephine biopsy on time of disease occurrence, the number of megakaryocyte in bone marrow smear less than 8/mm(2) was defined as group I, the number of megakaryocyte between 8/mm(2) to 15/mm(2) was defined as group II, the number of megakaryocyte greater than 15/mm(2) was defined as group III. The effective rate of these 3 groups in short term treatment were 53.8%, 85.0% and 90.3% respectively, group II and III had no statistical difference each other (p > 0.05), but both groups had statistical difference as compared with group I (p < 0.01). Effective rate of these 3 groups in long term treatment were 33.3%, 63.1% and 87.9% respectively, and there were statistical difference between them (p < 0.01). (5) the number of blood platelet at time of disease occurrence was not related to number of megakaryocyte in bone marrow smear and in trephine biopsy section(r = 0.31, p > 0.05; r = 0.41, p > 0.05). The number of megakaryocyte in bone marrow smear had positive correlation to that in trephine biopsy slides (r = 0.52, p < 0.01). In case to use single factor Logistic regression, the results showed that number of megakaryocyte in bone marrow smear and trephine biopsy had obvious influence on long term treatment of ITP. It is concluded that the number of megakaryocyte in trephine biopsy can be used as a available supplement method for bone smear, and can forecast the therapeutic effect of patients with ITP.

Experimental and clinical characteristics in myelodysplastic syndrome patients with or without HLA-DR15 allele.

We studied the effects of the presence of the HLA-DR15 allele on the experimental and clinical features of myelodysplastic syndrome (MDS) by assessing the clinical data of 136 patients with MDS. We observed that the frequency of HLA-DR15 expression in MDS patients (38.7%) was significantly higher than that in the healthy controls (p < 0.01). We noted the following observations with regard to disease progression: None of the 46 HLA-DR15 positive patients with international prognostic scoring system (IPSS) scores or=1.5 and the presence of >or=5% blasts in the bone marrow in the DR15-positive patients were lower than the corresponding findings in the DR15-negative patients. In addition, we also recorded the following observations with regard to bone marrow (BM) failure: The bicytopenia/pancytopenia ratio in the DR15-positive patients was higher than that in the DR15-negative patients (92.4 vs. 78.3%; p = 0.029). The peripheral-neutrophil count and the platelet count in the DR15-positive patients were lower than those in the DR15-negative patients (p = 0.028 and p = 0.011, respectively). Moreover, hypocellularity was more easily detectable in the DR15-positive patients (26.4 vs. 16.9%). In addition, the BM CD4+ lymphocyte count and the CD4/CD8 ratio in the DR15-positive patients were higher than the corresponding values in the DR15-negative patients (p < 0.05 for both). However, there were no significant differences between the polarization of T-helper (T(h)) and T-cytotoxic (T(c)) cells and the cytokine levels in these two patient groups. We concluded that the presence of the HLA-DR15 allele is indicative of a genetic susceptibility to MDS and, the presence of the HLA-DR15 allele showed less association with disease progression and greater association with BM failure.

Diagnosis of unknown nonhematological tumors by bone marrow biopsy: a retrospective analysis of 10,112 samples.

PURPOSE: To investigate how unselected bone marrow (BM) biopsy examinations could help in the diagnosis of clinically unknown nonhematological tumors. METHODS: 10,112 plastic-embedded BM biopsy sections were retrospectively analyzed. In the analysis we focused on the following aspects: (1) the frequency of BM involvement arising from clinically unknown nonhematological malignancies, (2) the clinical indication for BM biopsy examination in cases with tumor BM metastasis, (3) the primary sites of the metastatic tumors, and (4) the advantage of plastic-embedded biopsy sections over paraffin-embedded samples and the complementarity of biopsy with aspiration smears. RESULTS: Of the 10,112 BM samples analyzed, 101 (1.0%) were interpreted as being nonhematological tumor metastases. In cases with metastatic tumors, the nonhemocyte-related changes, such as skeletal pain (25%) and bone destruction (5%), were considerably higher than in those without metastasis (3.7 and 0.32%, respectively; P < 0.001). Primary lesions were documented antemortem in 50 of the 101 biopsy-positive cases (49.5%); the most frequent being in the lung, gastric tract, and breast. Using this assay, a higher incidence of metastatic tumors was detected when compared with previously reported paraffin-embedded samples. The frequency of metastatic tumors based on aspiration smears when the positive results for biopsy sections were used as a reference was 74.3%. All the 101 sections with metastatic tumors showed various degrees of myelofibrosis. CONCLUSIONS: We concluded that the routine BM biopsy examination is helpful in detecting insidious metastatic nonhematological malignancies. Skeletal pain and bone destruction are critical indications for susceptible patients to undergo BM examination. Plastic embedding of biopsy sections appears to be more sensitive than the paraffin embedding of samples and is an excellent complementation to isolated aspiration smears.

Synergic effects of bexarotene and TRAIL on apoptosis of leukemic cell line KG1a / 上海交通大学学报（医学版）

Objective To explore the effects and mechanism of bexarotene in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on apoptosis of leukemic cell line KG1a. Methods KG1a cells at logarithmic growth phase were obtained, and were divided into TRAIL group, bexarotene group, 300 ng/mL TRAIL in combination with bexarotene group and 2.0 μmol/L bexaroten in combination with TRAIL group. Cell apoptosis rate was detected in each group by flow cytometry. Flow cytometry was also employed to determine the apoptosis rates of KG1a cells after treatment with bexarotene and TRAIL in different sequences. The expression of Fas associated death domain-like IL-1 beta converting enzyme inhibitory protein (c-FLIP) was detected by Western blotting. Results There was no significant difference in cell apoptosis rates between TRAIL group and bexarotene group of each concentration (except for bexarotene 2.0 μmol/L) (P > 0.05). The cell apoptosis rates of 300 ng/mL TRAIL in combination with bexarotene group and 2.0 μmol/L bexaroten in combination with TRAIL group were significantly higher than those in TRAIL group and bexarotene group of each corresponding concentration (P <0.01). Sequential analysis revealed that bexarotene could reverse the resistance of KG1a cells to TRAIL (P < 0.001). Compared with single use of 2.0 μmol/L bexarotene or 300 ng/mL TRAIL, combination use could significantly down-regulated the expression of c-FLIP (P < 0.05). Conclusion Bexarotene can significantly enhance the apoptosis of KG1a cells induced by TRAIL, which may be attributed to the down-regulation of c-FLIP expression.

Preliminary study of biological characteristics of myelodysplastic syndromes clonal cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the biological difference of clonal cells between myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).</p><p><b>METHOD</b>Bone marrow (BM) clonal cells (which had cytogenetic markers detected by FISH assay) and blasts were quantitatively analysed in 51 MDS and 11 AML patients. The clonal cell percentage in orthochromatic normoblasts, granulocytes and megakaryocytes were assayed. The biological functions for phagocytosis and oxidation of MDS peripheral blood (PB) neutrophils were compared with that of normal controls.</p><p><b>RESULTS</b>Almost all MDS patients BM had a higher clonal cell percentage (mean 48.2%) than blasts percentage (mean 6.7%) (P < 0.01), but with the subtype of MDS advancing this percentage gap was closing up, and in 11 AML patients no such gap was observed. This gap in MDS patients with + 8 abnormality was smaller than in those with 5q -. In MDS BM, clonal cells were detected in segmented granulocytes (mean 45.9%), orthochromatic normoblasts (mean 46.0%) and mature megakaryocytes (mean 38.0%). In Addition, an approximate amount of clonal cells with the same karyotype abnormality in BM were detected in MDS PB (mean 37.3% in blood vs 48.6% in marrow). Functional analysis showed that the neutrophils in MDS PB could exert nearly normal physiological functions (P > 0.05), but those from AML could not as compared to healthy donors (P < 0.01).</p><p><b>CONCLUSION</b>There is a significant difference in the biological features between MDS and AML clonal cells.</p>

Abnormal polarization of T lymphocyte induces negative hematopoietic regulation in myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore polarization of T lymphocyte and its relationship with apoptosis of marrow cells in patients with myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>Measurements of Th1, Th2, Tc1, Tc2 subsets in bone marrows from 34 patients with MDS and 13 normal controls were performed by flow cytometry. INF-gamma and TNF-alpha in marrow serum were determined by ELISA (Enzyme-linked immunosorbent assay). Apoptosis index of marrow cells was detected by TUNEL (TdT-mediated dUTP nick end labeling). Correlations between Th1, Th2, Tc1, Tc2 subsets and INF-gamma, TNF-alpha levels as well as apoptosis index were analyzed, and relationship between TNF-alpha, INF-gamma levels and apoptosis index was also investigated.</p><p><b>RESULTS</b>(1) The percentage of Th1 cells [(10.1 +/- 1.6)%], Tc1 cells [(24.0 +/- 3.6)%] and Tc1/Tc2 ratio (50.0 +/- 11.1) was significantly increased in patients with MDS than in normal controls [(4.0 +/- 0.5)%, (5.8 +/- 0.6)% and 13.4 +/- 2.7, respectively]. Levels of INF-gamma [(58.6 +/- 21.7) microg/L] and TNF-alpha [(15.7 +/- 3.8) microg/L] in marrow serum of MDS patients was markedly elevated compared to normal controls [0 and (0.3 +/- 0.2) microg/L, respectively]. An increased apoptosis index of nucleated cells was observed in MDS patients [(7.8 +/- 1.5)%] as compared to controls [(2.1 +/- 0.3)%, P < 0.05]. The Th1 cell percentage showed a positive correlation with the levels of INF-gamma and TNF-alpha (r = 0.38, P < 0.05 and r = 0.39, P < 0.05, respectively), and with apoptotic index of nucleated marrow cells in MDS patients (r = 0.33, P < 0.05). Furthermore, a positive correlation was observed between INF-gamma, TNF-alpha levels and apoptotic index of marrow cells (r = 0.74, P < 0.01 and r = 0.73, P < 0.01, respectively). (2) Th1, Tc1 cells and Tc1/Tc2 ratio in MDS-RCMD patients was markedly elevated (P < 0.01) but did not in RCMD-RS, RAEB-1 and RAEB-2 patients as compared to normal controls. (3) An elevation in the percentages of Th1, Tcl and Tc1/ Tc2 ratio was detected in patients with IPSS lower-risk but did not in higher-risk group as compared to controls. (4) Increased Th1 and Tc1 percentages and Th1/Th2 and Tc1/Tc2 ratios were observed in RCMD patients with normal karyotype, but did not in those with abnormal karyotype. Conclusions Th1/Th2 and Tc1/Tc2 in bone marrow of MDS patients were unbalanced, polarizing to type I reaction especially in patients with RCMD subtype, IPSS lower-risk and normal karyotype. The increased Th1 cells in bone marrow may account for the increased apoptosis of nucleated marrow cells in MDS, through proapoptotic cytokines such as INF-gamma and TNF-alpha.</p>

Expression of type 1 insulin-like growth factor receptor in marrow nucleated cells in malignant hematological disorders: correlation with apoptosis.

To verify the expression of type 1 insulin-like growth factor receptor (IGF-IR) and its impact on hematopoietic cells apoptosis in myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML), marrow samples from 16 patients with MDS and 16 patients with AML were examined along with 16 healthy donors as controls. Immunocytochemical methods (alkaline phosphatase anti-alkaline phosphatase) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (fluorescence) were used simultaneously on nucleated cell cytospins. The ratio of IGF-IR positive cells and apoptotic cells as well as the relationship between them were then analyzed separately. A quantitative real-time reverse transcriptase-polymerase chain reaction (PCR) was administrated for six MDS cases and two normal controls to validate IGF-IR expression detected by immunochemistry. In our assay, IGF-IR appeared to have higher to lower expression rate in turn from AML (86.8+/-13.8%) to MDS (56.8+/-14.3%) and then to normal controls (40.4+/-9.6%) (P<0.01 between each group). In MDS nucleated cells, IGF-IR showed stronger expression in refractory anemia with excess blasts (RAEB)/RAEB in transformation/chronic myelomonocytic leukemia subgroup when compared to RA/RA with ringed sideroblasts cases (64.1+/-3.2 vs 53.5+/-16.2%) (P>0.05). Nucleated cells from MDS marrow underwent more apoptosis (5.4+/-3.0%) than that in normal marrow (1.2+/-0.9%) (P<0.01) and AML marrow (0.3+/-0.4%) (also, P<0.01 between each compared group). For both AML and MDS cases, apoptotic signals presented mainly in individual IGF-IR negative cells (9.0+/-4.8%) and less so in IGF-IR positive cells (1.4+/-2.4%) (P<0.01). When analyzed by groups, cell number with IGF-IR expression showed a negative correlation to apoptotic cells amount (r=-0.852; P<0.01) but positive correlation to their blast count (r=0.677; P<0.01). Outcome from real-time quantitative PCR appeared to have a trend of enhanced IGF-IR expression in advanced MDS subtypes. In conclusion, overexpression of IGF-IR existed in hematopoietic cells in MDS and AML marrows, which appeared to be contributed to disease progress.

Induction chemotherapy with low-dose homoharringtonine, cytarabine, and granulocyte colony-stimulating factor priming in patients with advanced myelodysplastic syndrome or post-myelody splastic syndrome acute myeloid leukemia / 中国医师进修杂志

20?10~9/L. This regimen was given for one course for induction, and was followed by conventional chemotherapy as maintenance or consolidation when complete remission(CR) achieved, or succeeding with other treatment when no response could be observed. Results Six patients achieved CR (54.5%) and one achieved partial remission (PR)(9.1%) with one course of treatment. Among 6 of 11 patients with CR, 5 relapsed at 2,3,6,8 and 16 months respectively. Three relapsed patients were retreated with the same protocol but achieved only one partial responses. Nine of the 11 patients had been died and their mean survival (since induction chemotherapy) was 9.2 months. Infectious complications during cytopenia were less serious than conventional chemotherapy withno treatment-related.Conclusion This moderate intensity protocol with G-CSF priming is effective and safe but remissions are of short duration.

Cytotoxicity of IFN-gamma-activated dendritic cells to freshly isolated acute myeloid leukemia cells / 中国实验血液学杂志

To investigate the tumoricidal activity of dendritic cell (DC) stimulated by interferon-gamma (IFN-gamma) against freshly isolated myeloid leukemia cells and its mechanism, the peripheral blood monocytes collected from healthy donors were cocultured with interleukin-4 and granulocyte-macrophage colony-stimulating factor in medium to induce DC for 7 days. After 12 hour culture in the absence or presence of IFN-gamma, the changes of costimulatory molecules were analyzed with flow cytometry. To assay the cytotoxicity of DC against freshly isolated acute myeloid cells, they were cocultured at various effector-to-target ratio for 18 hours, then the percentage of tumoricidal activity was measured with (51)Cr release assay. To explore the mechanism of DC-mediated cytotoxicity, the change of DC surface or intracellular protein expression of Fas ligand (Fas L), TNF-alpha and TNF related apoptosis-inducing ligand (TRAIL) were analyzed with flow cytometry. The results showed that IFN-gamma enhanced cytotoxicity of DC against AML cells was (33.8 +/- 1.6)% at E:T as 20:1, compared with unstimulated DC (P < 0.05); IFN-gamma up-regulated expression of costimulatory molecules of DC surface such as CD86 and CD83; after stimulation with IFN-gamma, expression of intracellular TRAIL of DC was significantly enhanced, but expression of TRAIL on cell surface of DC was low; while the significant changes of Fas L and TNF-alpha expression neither on cell surface or in cells were not observed before or after stimulation with IFN-gamma. It is concluded that DC stimulated by IFN-gamma exhibit tumoricidal activity against AML cells. The cytotoxicity is partially related to maturation of DC and TRAIL inducing apoptosis, but not associated with death domain-independent mechanism of Fas L and TNF-alpha.