Comparision of Allogeneic Hematopoietic Stem Cell Transplantation between Children with Thalassemia of Different Ages / 中国实验血液学杂志

OBJECTIVE@#To investigate the difference of therapeutic effects on children with thalassemia at different age after hematopoietic stem cell transplantation.@*METHODS@#The clinical data of children with thalassemia treated in our hospital were retrospectively analyzed. The children were divided into 2-5 years old group and 6-12 years old group. The success rate of implantation, transplant-related mortality, GVHD incidence, and other transplant-related complications, as well as thalassemia-free survival (TFS) were compared between the two groups.@*RESULTS@#The incidence of GVHD, hemorrhagic cystitis and severe oral mucositis after transplantation in the 2-5 years old group were significantly lower than those in the 6-12 years old group, while there was no statistically significant difference in the TFS between the two groups.@*CONCLUSION@#Children in the low age (2-5 years old) group show fewer complications and higher quality of life after transplantation, therefore, stem cell transplantation at 2-5 years old is more conducive to rehabilitation of the children with thalassemia.

The Clinical Efficacy of Haploidentical Hematopoietic Stem Cell Transplantation by Using Parental Donors in Patients with Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) by using parental donors on thalassemia patients.@*METHODS@#The 13 thalassemia patients treated by haplo-HSCT using parental donors in our hospital from July 1, 2016, to July 1, 2020 were retrospectively reviewed. Hematopoiesis reconstitution, the incidence of GVHD, infections and the long-term survival of the patients were analyzed.@*RESULTS@#Twelve of the 13 patients were successfully implanted, the success rate of implantation was 92.3%. The median time of neutrophil and platelet engraftment was 12.5 days (range, 9-22 days) and 21 days (range,12-34 days), respectively. One patient achieved primary graft failure. Three (25%) patients developed to acute GVHD (aGVHD) and achieved complete remission after treatment. Chronic GVHD developed in three (25%) patients, one of them was extensive and under treatment, while one patient developed to severe bacterial infection (7.7%). CMV viremia was diagnosed in two patients (15.4%). There were no patients developed to CMV disease. Three (23.1%) patients achieved EB viremia after transplantation, one of them developed to EBV-related lymphocytic proliferative disease, while there were no patients showed invasive fungal infection. At the last follow-up, all patients survived, twelve of them were free from transfusion dependency. There were no transplant-related deaths. Projected overall and thalassemia-free survival at three years was 100% and 92.3%, respectively.@*CONCLUSION@#The transplant protocol of haplo-HSCT by using parental donors in patients with thalassemia has reliable source of donors, high incidence of successful implantation and low incidence of GVHD, which can be used as an effective way to increase the source of donors in children with thalassemia.

Epidemiological characteristics of imported COVID-19 cases in Beijing / 中华流行病学杂志

Objective: To analyze the epidemiological characteristics of imported COVID-19 cases and the effect of vaccination on virus load and disease severity of the cases in Beijing. Methods: The data of the imported COVID-19 cases in Beijing were collected from the National Notifiable Infectious Disease Reporting System of China Information for Disease Control and Prevention and Epidemiology investigation. The data were processed and analyzed by Excel 2010 and SPSS 22.0. Results: From June 1 to September 30, 2021, a total of 171 imported COVID-19 cases were reported in Beijing, of which 66.67% (114/171) were asymptomatic. The cases were mainly from the Philippines, the United Arab Emirates, the United Kingdom and the Russian Federation, accounting for 67.84% (116/171). The male to female ratio of the cases was 2∶1 (114∶57). The median age M (Q1, Q3) of the cases was 28 (23, 36) years. The cases of Chinese accounted for 80.12% (137/171). The sequencing of the whole genome of the virus in 47 imported COVID-19 cases showed that the proportion of Delta variant was 76.60% (36/47). The COVID-19 vaccination coverage rate in the cases was 60.82% (104/171), but the full vaccination coverage rate was 53.80% (92/171). In the imported COVID-19 cases, 13.53% (23/170) were screened to be SARS-CoV-2 nucleic acid positive on the day when they arrived in Beijing, and all the cases were positive for 2019-nCoV nucleic acid within 28 days. The severity of the disease was higher in the unvaccinated group than in the partially vaccinated group and fully vaccinated group (P<0.001). In the unvaccinated group, there were 1 severe case and 1 critical case. The median Ct values M (Q1, Q3) of N gene and ORFlab gene in unvaccinated group were 32.51 (23.23, 36.06) and 32.78 (24.00, 36.38), respectively. There was no significant difference in the median of double-gene Ct value between the partially vaccinated group and the fully vaccinated group. Conclusions: During the study period, most of the imported COVID-19 cases in Beijing were asymptomatic. No matter vaccinated or not, the viral loads in the COVID-19 cases were similar, but the vaccination could reduce the severity of the disease.

Epidemiological characteristics of hand, foot and mouth disease among people aged 6 and over in Beijing, 2011-2020 / 中华流行病学杂志

Objective: To analyze the epidemiological characteristics of hand, foot and mouth disease (HFMD) among people ≥6 years old in Beijing from 2011 to 2020. Methods: The incidence data of HFMD cases from 2011 to 2020 were collected from the National Notifiable Infectious Disease Reporting System of China Information for Disease Control and Prevention and the etiological surveillance of HFMD in 29 sentinel hospitals from 16 districts of Beijing. Descriptive epidemiological methods were used to analyze the distributions, pathogen constituents, and changes of HFMD cases in Beijing people ≥6 years old. Results: From 2011 to 2020, a total of 38 183 cases of HFMD were reported among people ≥6 years old in Beijing, of which 46 (0.12%) cases were severe. The average annual reported incidence was 19.04/100 000. The ratio of males to females were 1.37∶1(22 064∶16 119). The proportion of HFMD in people ≥6 years old increased from 7.56%(2 606/34 488) in 2011 to 24.54% (546/2 225) in 2020. The average incidence of HFMD was higher in Shunyi district, Yanqing district, and Tongzhou district than in other districts in Beijing. The positive rate of enterovirus in sentinel surveillance was 66.78% (1 976/2 959), the proportion of enterovirus group A 71 (EV-A71) was 45.29% (101/223) in 2014, no EV-A71 positive was detected in 2020, and the proportion of Coxsackievirus A 6 (CV-A6) increased from 15.11% (34/225) in 2016 to 81.08% (60/74) in 2020. Conclusions: From 2011 to 2020, the proportion of cases with HFMD in people ≥6 years old in Beijing increased yearly, and the proportion of EV-A71 positive patients decreased basically. Since 2016, CV-A6 has gradually become the dominant pathogen. More attention should be paid to the epidemic situation and dynamic pathogen changes of hand foot mouth disease in people ≥6 years old.

Application of two RT-PCR methods for detection of norovirus in market-sold oysters and norovirus genetic characteristic analysis, a survey conducted in Beijing / 中华流行病学杂志

Objective: To evaluate the application of real-time RT-PCR and semi-nested RT-PCR in the detection of norovirus in oysters and analyzing the genetic characteristics of the isolates. Methods: Real-time fluorescent RT-PCR and semi-nested RT-PCR were used to detect norovirus GⅠ/GⅡ in fresh oysters collected from the markets in Beijing from November 2014 to October 2015. The detection rate of the parallel test was also analyzed. In addition, the reliability of semi-nested RT-PCR was evaluated by agreement rate and consistency test (Kappa value). The positive products of norovirus GⅠ/GⅡ capsid protein region gene by semi-nested RT-PCR were sequenced. Software BioEdit 7.0.9.0 was used for sequence alignment, and software Mega 6.0 was used to construct the evolutionary tree. Results: In 72 samples, the detection rate of norovirus was 31.94% (23/72) by real-time RT-PCR, 38.89% (28/72) by semi-nested RT-PCR and 48.61% (35/72) by parallel test. The coincidence rate of the two methods was 73.61%, a moderate degree (Kappa value =0.43). A total of 13 norovirus strains were successfully sequenced, and 11 strains (7 GⅡ.17 strains, 2 GⅡ. 4 Sydney_ 2012 strains, 1 GⅡ. 1 strain and 1 GⅡ. 21 strain) were obtained from norovirus positive samples by two RT-PCR methods, two strains (1 GⅡ. 17 strain and 1 GⅡ. 3 strain) were obtained from real-time RT-PCR negative samples which were positive for norovirus by semi-nested RT-PCR. The similarity between these strains and reference strains from diarrhea patients, environmental sewage, and shellfish products were 84.4% - 100.0%. Conclusions: The parallel test of norovirus in oysters by two RT-PCR methods can improve the detection rate and detect more genotypes. Norovirus strains in oysters were highly homologous with reference strains from diarrheal patients, environmental sewage, and shellfish products. Therefore, surveillance, prevention and control for norovirus should be carried out in people who have frequent contacts with oysters and related environments.

Plasma MiR-181b and MiR-194 As Biomarkers for Acute Graft- Versus-Host Disease and Significance of Their Changes / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical correlation of expression level changes of miR-181b and miR-194 to the pathogenesis of acute graft-versus-host disease (aGVHD), and determine plasma miR-181b and miR-194 as the potential biomarkers for aGVHD.@*METHODS@#The plasma samples were collected from 31 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at before HSCT, 15 days after HSCT and onset of aGVHD. The expression levels of miR-181b and miR-194 were detected by quantitative real-time PCR. Receiver-operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to assess the sensitivity and specificity of miRNA biomarkers for the diagnosis of aGVHD.@*RESULTS@#MiR-181b and miR-194 downregulated after treatment were significantly upregulated in the plasma at onset of aGVHD (P0.05). The expressions of plasma miR-181b and miR-194 collected on day 15 after HSCT were significantly upregulated in the patients with aGVHD in comparison with non-GVHD patients (P<0.05). Moreover, these elevated miRNAs were detected before aGVHD. The AUC of miR-181b predicting aGVHD was 0.91±0.05 (specificity was 0.94, sensitivity was 0.69). The AUC of miR-194 predicting aGVHD was 0.91±0.06 (specificity was 0.94, sensitivity was 0.77).@*CONCLUSION@#MiR-181b and miR-194 may serve as early biomarkers for the diagnosis and prognosis of aGVHD.

Efficacy evaluation of modified lamina osteotomy replantation versus traditional lamina osteotomy replantation in treating lumbar disc herniation with lumbar instability / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the clinical effects of modified lamina osteotomy replantation versus traditional lamina osteotomy replantation in the treatment of lumbar disc herniation with lumbar instability.</p><p><b>METHODS</b>The clinical data of 146 patients with unilateral lumbar disc herniation with lumbar instability underwent surgical treatment from March 2008 to March 2013 were retrospectively analyzed. Patients were divided into two groups according to osteotomy replantation pattern. There were 77 patients in the traditional group (underwent traditional lamina osteotomy replantation), including 42 males and 35 females with an average age of (49.4±18.5) years;the lesions occurred on L₄,₅ in 46 cases, on L₅5S₁ in 31 cases. There were 69 patients in modified group (underwent modified lamina osteotomy replantation), including 37 males and 32 females with an average age of (49.8±17.9) years;the lesions occurred on L₄,₅ in 40 cases, on L₅S₁ in 29 cases. The operation time, intraoperative blood loss, complication rate during operation, lamina healing rate, recurrence rate of low back and leg pain were compared between two groups. Visual analogue scales (VAS) and Japanese Orthopadic Association (JOA) scores were used to evaluate the clinical effects.</p><p><b>RESULTS</b>The operation time and intraoperative blood loss were similar between two group (>0.05). There was significantly different in nerve injury rate(5.80% vs 16.9%) and dural injury rate(1.45% vs 9.09%) between modified group and traditional group(<0.05). The recurrent rate of low back pain of modified group was higher (91.30%, 63/69) than that of traditional group (76.62%, 59/77), and the intervertebral fusion rate of modified group was lower(8.70%, 6/69) than that of traditional group (29.9%, 23/77) at 3 years after operation. Postoperative VAS scores of all patients were significantly decreased at 6 months, 1, 2, 3 years, and JOA scores were obviously increased (<0.05). At 1, 2, 3 years after operation, VAS scores of modified group were significantly lower than that of traditional group(<0.05), and JOA scores of modified group were higher than that of traditional group(<0.05).</p><p><b>CONCLUSIONS</b>Modified lamina osteotomy replantation has better long-term efficacy(in the aspect of recurrent rate of low back pain, intervertebral fusion rate, VAS and JOA score at three years follow-up) in treating lumbar disc herniation with instability.</p>

Impact of one-child on body mass index and percentage of body fat in primary school students: a longitudinal study / 上海交通大学学报（医学版）

Objective·To evaluate the impact of one-child on body mass index (BMI), and percentage of body fat in primary school students. Methods·All the sample was recruited from 5 elementary schools in Gaohang Town, Shanghai, China. The baseline data of height, body weight, and percentage of body fat was obtained in 2013, and re-measured in 2014 and 2015, respectively. Birth weight, breast feeding, diet and time for physical activities of each children and the highest education level, height, and body weight of their parents were also collected by a self-completed questionnaire. Logistic regression and Mix model was used to analyze the relationship between one-child and BMI, BMI-Z score, and percentage of body fat. Results·A total number of 2515 (1323 boys and 1192 girls) primary school students completed the study and entered the analysis. The percent of one child in this study population was 72.0％ (1812/2515). BMI-Z score, time for physical activities, parental education level, and maternal BMI were higher, while the rate of breast feeding was lower in one-child group compared to non-one-child group. The results of Logistic regression showed boys (compared to girls), macrosomia ( ≥4000g vs normal birth weight), overweight father and mother (compared to normal BMI) were risk factors for overweight. The factor of one-child didn't increase the risk of overweight (OR=1.119, 95％ CI 0.911-1.374). After potential con-founders adjusted, the annual increase of BMI (β=0.028, 95％ CI -0.045-0.100), BMI-Z score (β=0.002, 95％CI -0.034-0.037) and percentage of body fat (β=0.013, 95％ CI -0.181-0.207) showed no obvious difference between the two groups. Conclusion·One-child factor showed no obvious relationship with BMI, BMI-Z score and percentage of body fat in primary school students.

Notch1 Gene Silenced by RNAi Inhibits Oncogenicity of Myeloma Cell Line / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Notch1 gene silencing by RNA interference on oncogenicity of multiple myeloma cells in NOD/SCID mice.</p><p><b>METHODS</b>Targeting-silenced Notch1 gene was target-sotenced by transfection of Notch1-shRNA in multiple myeloma RPMI8226 cells of NOD/SCID mouse myeloma models, and the change of the volume and speed of oncogenicity in myeloma mouse models were evaluated after Notch1 gene silencing, and ELISA was used to detect the serum expression level of IL-6 and VEGF in the tumor-bearing mice.</p><p><b>RESULTS</b>After Notch1 gene was silenced by Notch1-shRNA, the speed of tumor formation was significantly inhibited and the tumor volume was reduced in the tumor-bearing mice, as compared with the control group, and the difference was statistically significant (P<0.05). The serum level of IL-6 and VEGF in the tumor-bearing mice significantly decreased in comparison with the control group (P<0.05 ).</p><p><b>CONCLUSION</b>The oncogenicity of myeloma cells in the models NOD/SCID mouse myeloma is significantly inhibited by Notch1 gene-silencing, and its mechanism may relate with the decreased secretory level of IL-6 and VEGF after Notch1 gene silencing. Notch1 gene silencing can be used as a new strategy to treat multiple myeloma.</p>

Targeting Notch1 Gene Inhibits the Proliferation of Multiple Myeloma Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Notch1 gene silencing on the proliferation and apoptosis of multiple myeloma cells, and to find the new targets for the treatment of multiple myeloma.</p><p><b>METHODS</b>Notch1-shRNA targeted silencing Notch1 gene was transfected into multiple myeloma RPMI8226 cells, the CCK-8 and flow cytometry were used to detect the proliferation and apoptosis of myeloma cells after Notch1-shRNA transfection, the real-time fluorescence quantitative PCR was used to analyze expression level of Notch1 mRNA, and the Western blot were used to detect the expression level of Notch1 signaling pathway-related protein, such as Hes-1, Jagged-1, Jagged-2, BCL-2, PTEN, AKT and P-AKT.</p><p><b>RESULTS</b>The mRNA and protein expression levels of Notch1-shRNA transfected cells were significantly inhibited in the experimental group assayed by real time fluorescence quantitative PCR and Western blot, the mRNA and protein expression level were down-regulated to 66% + 0.1%, 88% + 3.4% respectively, as compared with the control group(P<0.05). CCK-8 results confirmed that the cell proliferation rate was significantly decreased in the experimental group 48 hours after transfection. Flow cytometry results showed that the cell apoptosis rate was significantly higher in the experimental group than that in the control group. The expression levels of downstream protein Hes1, p-AKT and BCL-2 were decreased, the level of PTEN increased significantly after Notch1 gene silencing.</p><p><b>CONCLUSION</b>Notch1 gene silencing by transfection of Notch1-shRNA can inhibit the proliferation of myeloma cells and induce their apoptosis, and its mechanism is related to the activation of PTEN gene and p-AKT signaling. Notch1 signal can be used as a potential target for multiple myeloma therapy.</p>

Research Progress on the Drug Resistance Mechanism of Acute Myeloid Leukemia Mediated by the MicroRNA -Review / 中国实验血液学杂志

The acute myeloid leukemia is a very common malignant tumor of hematopoietic system, which is seriously harmful to human health. The long-term survival rate of routine chemotherapy is not satisfactory, especially in the high risk patients. Resistance to chemotherapy drugs is one of the major reasons, which causes the refractorines and relapse of the acute myeloid leukemia. The microRNA found in eukaryote is an endogenous non-coding micromolecular signle-stranded RNA of 19 to 25 nt. The miRNA can degrade the specific RNA or inhibit its translation through combining to 3' untranslated regions of the specific RNA, which contributes to regulate the expression of the target gene. There are already some evidences showing that the disorder of miRNA plays an important role in the genesis and progress of the tumors. Recently, more and more researches suggest that the miRNA is also important in the genesis of drug resistance to tumors. This review summarizes the research progress and the major mechanism of drug-resistance mediated by the miRNA in AML, including multiple drug resistance, cell cycle and the tolerance to apoptosis, all of which are associated with ABC transport protein.

Effect of Hedgehog Signaling Pathway Abnormality on Chemothe-rapeutic Resistance of Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the correlation between the excessive activation of Hedgehog signal and the drug resistance of multiple myeloma.</p><p><b>METHODS</b>The resistant cell line RPMI 8226/R of multiple myeloma was established by an ascending concentration gradient method. The experiment consisted of 4 groups: RPMI8226/R, RPMI8226/S, GANT61+RPMI8226/R and GANT61+RPMI8226/S. The CCK-8 (cell counting kit-8) assay was used to detect the cell proliferation inhibition rate in 4 groups; the RT-PCR was used to detect the expression of Gli1, Gli2, Shh, Ihh, Smo and Sufu in the RPMI8226/S and RPMI8226/R cells. The Western blot was used to detect the expression of the resistant protein Cyclin D1, P21 and BCL-2 and MDR-related signaling pathways protein p-Akt, p-MAPK and STAT3 in the RPMI8226/S and RPMI8226/R cells. After adding different concentration of GANT61, the Western blot was used to detect the expression of Gli2 in RPMI8226/R and RPMI8226/S cells.</p><p><b>RESULTS</b>The expression of Shh, Ihh, Smo Gli2 was enhanced significantly in the RPMI8226/R cells, but the expression of Sufu inhibitor was reduced, the expression level of related protein in Hedgehog signaling pathway was significanly higher in RPMI8226/R than that in RPMI8226/S. After theatment of GANT61 in vitro, the expression level of Gli2 in multiple myelom cells obviously decreased, the decreasing effect of GANT61 on Gli2 expression in RPMI8226/R cells was more significant than that in RPMI8226/S cells. The sensitivity of RPMI8226/R cells to DOX after treatment with GANT61 (IC) was risen from 7.11±0.061 µmol/L to 0.99±0.053 µmol/L, the corresponding cell resistance index decreased from 5.51 to 1.69.</p><p><b>CONCLUSION</b>the activation of Hedgehog signaling pathway is closely related with the resistance of multiple myeloma cells, and GANT61 can block the Hedgehog signaling pathway, thus Hedgehog signaling may be used as a new target for multiple myeloma treatment.</p>

Circulating Serum MicroRNA as Diagnostic Biomarkers for Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the diagnostic value of circulating serum miRNA for multiple myeloma.</p><p><b>METHODS</b>Forty blood samples from patients with multiple myeloma were collected from July 2013 to June 2014 in Department of Hematology, Zhongshan Hospital Affiliated to Xiamen University. The real-time quantitative PCR was performed to detect the serum expression levels of miRNAs (miR-29a, miR-155, miR-16 and miR-92a) circulating in the different stages of patients with multiple myeloma and evaluate the diagnostic value for patients with multiple myeloma.</p><p><b>RESULTS</b>The serum level of miR-29a significantly increased in newly diagnosed patients as compared to healthy donor (P<0.01), serum miR-155 levels were significantly lower as compared with healthy donor(P<0.001); The ratio of miR-29a and miR-155 was an effective biomarker for distinguishing multiple myeloma from healthy donor, their sensitivity and specificity were 80.8% and 83.3% respectively for myeloma diagnosis. the change of miR-29a expression was consistent with the changes of bone marrow plasma cells and M protein levels.</p><p><b>CONCLUSION</b>These circulating serum microRNA, such as miR-29a, miR-155 and miR-16, may serve as potential diagnostic biomarkers for multiple myeloma, and the ratio of miR-29a/miR-155 may serve as a most useful biomarker for myeloma diagnosis.</p>

Toxicology and bioactivities of CO-releasing molecules based on cobalt complexes / 药学学报

Complexes containing cobalt and carbon monoxide ligands, CO releasing molecules (CORMs), have the potential of anti-tumor and anti-inflammatory. In this paper, three hybrid CORMs 1-3 were synthesized and tested for their toxicology in vivo and bioactivities. The results suggest that the complexes have a long half-life in the range of 43-53 min; their oral LD50 to mouse are between 1 500 mg·kg-1 and 5 000 mg·kg-1. After the successive administration, complex 1 exhibited a toxic activity in rats' liver, and induced an injury to liver cells. Complex 1 had a strong growth inhibition activity (IC50 36.20 μmol·L-1 and 39.25 μmol·L-1) in both HeLa cells and HepG2 cells, complex 2 displayed a lower activity in the inhibition of HeLa cells proliferation than the control 5-FU (IC50 114.19 μmol·L-1), but had a higher activity in the inhibition of HepG2 cells than the control 5-FU (IC50 171.34 μmol·L-1). The anti-inflammatory study suggests that all of them reduce intracellular nitrite level, complexes 1 and 2 have a stronger activity than complex 3. Their anti-inflammatory activity attributes to the CO molecules of the CORMs, which was confirmed by comparison with the corresponding ligand.

Effects of DNMT1 Gene Silencing on Methylation of SOCS-1 Gene in Myeloma Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of DNA methyhransferase l (DNMT1) gene silencing on methylation of suppressor of cytokine signaling (SOCS-1) in multiple myeloma RPMI 8226 cells.</p><p><b>METHODS</b>Recombinant plasmid pshRNA-DNMTl was transfected into multiple myeloma RPMI 8226 cells by lipofectamine 2000. RT-PCR and Western blot were used to detect the mRNA and protein expression of DNMTl in RPMI 8226 cells respectively before and after transfection. Methylation-specific polymerase chain reaction was used to detect the methylation level change of SOCS-1 gene in RPMI8226 cells transfected.</p><p><b>RESULTS</b>DNMTl targeted short hairpin RNA(shRNA) was successfully inserted into the plasmid vector pshRNA. RT-PCR results showed that the relative mRNA expression level of DNMTI gene in RPMI 8226 cells transfected with pshRNA was 0.176±0.004 which was significantly lower than that in cells transfected by empty vector (0.956±0.033, P<0.01). Western blot analysis showed that the relative expression level of DNMT1 protein of RPMI 8226 cells transfected by pshRNA was 0.065±0.014, which was significantly lower than that in transfected cells by empty vector(0.415±0.027) (P<0.05). These results indicated that the recombinant plasmid pshRNA could effectively knock down the expression of DNMT1 gene in RPMI 8226 cells. Methylation analysis showed that the methylation level of SOCS-1 gene was obviously reduced after transfection.</p><p><b>CONCLUSION</b>DNMT1 gene in RPMI 8226 cell can be silenced by shRNA. DNMT1 gene silencing can significantly induce SOCS-1 gene hypomethylation, which indicates that DNMT1 may play an important role in the process of SOCS-1 hypermethylation.</p>

A novel prognostic score for acute-on-chronic hepatitis B liver failure / 华中科技大学学报（医学）（英德文版）

Patients with acute-on-chronic hepatitis B liver failure (HBV-ACLF) show high morbidity and mortality. Independent prognostic predictors of short-term HBV-ACLF mortality include the Child-Turcotte-Pugh (CTP) score, the model for end-stage liver disease (MELD) score, other MELD-based indices and the dynamic changes in these indices. The aims of this study were to evaluate the existing prognostic scores in a large cohort of HBV-ACLF patients and create a new predictive model. We retrospectively reviewed 392 HBV-ACLF patients from December 2008 to November 2011 and evaluated their 3-month survival. The predictive accuracy of CTP, MELD and MELD-based indices and the dynamic changes in the MELD-related scores (Δ scoring systems) upon admission and after two weeks of treatment were compared using the area under the receiver operating characteristic (ROC) curve method. Life-threatening factors and a series of bio-clinical parameters were studied by univariate and multivariate analyses. Among the existing scores, MELD had the best predictive ability. However, our new regression model provided an area under the curve of 0.930±0.0161 (95% CI: 0.869 to 0.943), which was significantly larger than that obtained with the MELD score at admission and after two weeks of treatment as well as with the dynamic changes of the MELD score (0.819, 0.921, and 0.826, respectively) (Z=3.542, P=0.0004). In a large cohort of patients retrospectively reviewed for this study, our prognostic model was superior to the MELD score and is, therefore, a promising predictor of short-term survival in patients with HBV-ACLF.

A novel prognostic score for acute-on-chronic hepatitis B liver failure / 华中科技大学学报（医学）（英德文版）

Patients with acute-on-chronic hepatitis B liver failure (HBV-ACLF) show high morbidity and mortality. Independent prognostic predictors of short-term HBV-ACLF mortality include the Child-Turcotte-Pugh (CTP) score, the model for end-stage liver disease (MELD) score, other MELD-based indices and the dynamic changes in these indices. The aims of this study were to evaluate the existing prognostic scores in a large cohort of HBV-ACLF patients and create a new predictive model. We retrospectively reviewed 392 HBV-ACLF patients from December 2008 to November 2011 and evaluated their 3-month survival. The predictive accuracy of CTP, MELD and MELD-based indices and the dynamic changes in the MELD-related scores (Δ scoring systems) upon admission and after two weeks of treatment were compared using the area under the receiver operating characteristic (ROC) curve method. Life-threatening factors and a series of bio-clinical parameters were studied by univariate and multivariate analyses. Among the existing scores, MELD had the best predictive ability. However, our new regression model provided an area under the curve of 0.930 ± 0.0161 (95% CI: 0.869 to 0.943), which was significantly larger than that obtained with the MELD score at admission and after two weeks of treatment as well as with the dynamic changes of the MELD score (0.819, 0.921, and 0.826, respectively) (Z=3.542, P=0.0004). In a large cohort of patients retrospectively reviewed for this study, our prognostic model was superior to the MELD score and is, therefore, a promising predictor of short-term survival in patients with HBV-ACLF.

Prophylactic Antitumor Effect of Mixed Heat Shock Proteins/Peptides in Mouse Sarcoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>To develop a vaccine-based immunotherapy for sarcoma, we evaluated a mixture of heat shock proteins (mHSPs) as a vaccine for sarcoma treatment in a mouse model. Heat shock protein/peptides (HSP/Ps) are autoimmune factors that can induce both adaptive and innate immune responses; HSP/Ps isolated from tumors can induce antitumor immune activity when used as vaccines.</p><p><b>METHODS</b>In this study, we evaluated the effects of mHSP/Ps on prophylactic antitumor immunity. We extracted mHSP/Ps, including HSP60, HSP70, GP96, and HSP110, from the mouse sarcoma cell lines S180 and MCA207 using chromatography. The immunity induced by mHSP/Ps was assessed using flow cytometry, ELISPOT, lactate dehydrogenase release, and enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>Of S180 sarcoma-bearing mice immunized with mHSP/Ps isolated from S180 cells, 41.2% showed tumor regression and long-term survival, with a tumor growth inhibition rate of 82.3% at 30 days. Of MCA207 sarcoma-bearing mice immunized with mHSP/Ps isolated from MCA207 cells, 50% showed tumor regression and long-term survival with a tumor growth inhibition rate of 79.3%. All control mice died within 40 days. The proportions of natural killer cells, CD8+, and interferon-γ-secreting cells and tumor-specific cytotoxic T-lymphocyte activity were increased in the immunized group.</p><p><b>CONCLUSIONS</b>Vaccination with a polyvalent mHSP/P cancer vaccine can induce an immunological response and a marked antitumor response to autologous tumors. This mHSP/P vaccine exerted greater antitumor effects than did HSP70, HSP60, or tumor lysates alone.</p>

Molecular mechanism of Doxorubicin resistance in multiple myeloma cell line / 中国实验血液学杂志

This study was aimed to investigate the molecular mechanism of doxorubicin resistance in multiple myeloma cell line and certify the effect of Notch signal over-expression on drug resistance of myeloma cells. The doxorubicin RPMI 8226 cell line (RPMI8226/DOX) was established by culturing 8226 cells with continuous low concentration and intermittent gradually-increasing-concentration of doxorubicin in vitro, the mRNA expression of Notch2,Jagged1, Jagged2, HES1 were measured by RT-PCR and the P-170 protein expression was detected by Western blot in RPMI 8226 cell line; the changes of IL-6 and VEGF were tested by ELISA. The results showed that the Notch mRNA expression (Notch2, Jagged1, Jagged2 increased gradually along with the increase of chemotherapeutic drug resistance, but the expression of HESI mRNA gradually decreased along with the increase of drug resistance. The expression level of P-170 protein was upregulated gradually along with the increase of drug resistance. The level of VEGF and IL-6 in culture supernatants of RPMI8226/DOX was higher than that in RPMI 8226. It is concluded that the establishment of RPMI 8226/DOX cell line is a useful model to analyze the mechanism of chemotherapeutic drug resistance in multiple myeloma, Notch activation is closely correlated with the drug resistance of multiple myeloma and Notch signaling may to be used as a new target for multiple myeloma treatment.

Lyme Borreliosis-associated Risk Factors in Residents of Beijing Suburbs: a Preliminary Case-control Study / 生物医学与环境科学（英文）

A population-based case-control study was conducted to evaluate the relative factors in the environments, agricultural works, outdoor activities, and the effectiveness of Lyme borreliosis (LB)- associated personal protective measures in Beijing. Thirty-four cases and 272 controls were personally interviewed by well-trained interviewers. Venous blood samples were taken from each subject. Sowing or harvesting in summer (OR=2.571, 95% CI: 1.109-5.962), living in house with weeding in the yard (OR=2.247, 95% CI: 1.062-4.755), and residence at the plain area (OR=2.630, 95% CI: 1.050-6.588) were the independent relative factors for seropositive LB. Wearing long pants and clothes with cuffs was the only protective behavior against tick bite (OR=0.186, 95% CI: 0.041-0.846). The findings showed that local farmers were easily infected with LB and almost no protective measure was taken against LB infection. Infection with LB was easier in residents of plain regions. Pets raising and outdoor activities were not the risk factors for infection with LB. Further studies are needed to fully understand the risk of infection with LB in China.