Genomic and Transcriptomic Characterization Revealed the High Sensitivity of Targeted Therapy and Immunotherapy in a Subset of Endometrial Stromal Sarcoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The unique chromosomal rearrangements of endometrial stromal sarcoma (ESS) make it possible to distinguish high-grade ESS (HGESS) and low-grade ESS (LGESS) from the molecular perspective. Analysis of ESS at the genomic and transcriptomic levels can help us achieve accurate diagnosis of ESS and provide potential therapy options for ESS patients. @*Materials and Methods@#A total of 36 ESS patients who conducted DNA- and/or RNA-based next-generation sequencing were retrospectively enrolled in this study. The molecular characteristics of ESS at genomic and transcriptomic levels, including mutational spectrum, fusion profiles, gene expression and pathway enrichment analysis and features about immune microenvironment were comprehensively explored. @*Results@#TP53 and DNMT3A mutations were the most frequent mutations. The classical fusions frequently found in HGESS (ZC3H7B-BCOR and NUTM2B-YWHAE) and LGESS (JAZF1-SUZ12) were detected in our cohort. CCND1 was significantly up-regulated in HGESS, while the expression of GPER1 and PGR encoding estrogen receptor (ER) and progesterone receptor (PR) did not differ significantly between HGESS and LGESS. Actionable mutations enriched in homologous recombination repair, cell cycle, and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways were detected in 60% of HGESS patients. Genes with up-regulated expression in HGESS were significantly enriched in five immune-related pathways. Most HGESS patients (85.7%) had positive predictors of immunotherapy efficacy. Moreover, immune microenvironment analysis showed that HGESS had relatively high immune infiltration. The degree of immune infiltration in HGESS patients with ZC3H7B-BCOR fusion was relatively higher than that of those with NUTM2B-YWHAE fusion. @*Conclusion@#This study investigated the molecular characteristics of ESS patients at the genomic and transcriptomic levels and revealed the potentially high sensitivity of targeted therapy and immunotherapy in a subset of HGESS with specific molecular features, providing a basis for guiding decision-making of treatment and the design of future clinical trials on precision therapy.

Outcome of children with T cell acute lymphoblastic leukemia treated with Chinese Children Leukemia Group acute lymphoblastic leukemia (CCLG-ALL) 2008 protocol / 中华儿科杂志

Objective@#To evaluate the efficacy of the Chinese Children′s Leukemia Group (CCLG) acute lymphoblastic leukemia (ALL) 2008 protocol (CCLG-ALL 2008) in the treatment of children′s T-cell acute lymphoblastic leukemia (T-ALL).@*Methods@#Clinical characteristics and outcomes of 84 newly diagnosed T-ALL children (63 males and 21 females) treated with CCLG-ALL 2008 protocol from April 2008 to April 2015 in the Department of Pediatric Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences were analyzed retrospectively. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and event free survival (EFS), and COX regression was used to evaluate the influencing factors of OS and EFS.@*Results@#(1) Baseline data: 84 children were included, 56 cases (67%) of children were younger than 10 years old. Patients whose white blood cell count≥50×109/L ranked 70% (59/84). Karyotype: 58% (49/84) with normal karyotype, 10% (8/84) with abnormality of chromosome 11, 8%(7/84) with abnormality of chromosome 9, 2%(2/84) with abnormality in both chromosome 11 and chromosome 9, 8% (7/84) with other complex karyotypes. Fusion gene: 33%(28/84) were SIL-TAL1 positive. The patients were grouped by CCLG-ALL 2008 risk score, 40% (34/84) were in the intermediate risk group and 60% (50/84) in the high risk group. (2) Treatment efficacy: 84 cases were followed up until May 30, 2018. The follow-up time was 42.0 (0.3-120.0) months. The sensitivity rate of prednisone treatment was 56% (47/84); the complete response (CR) rate after the induction therapy of vincristine+daunoblastina+L-asparaginase+dexamethasone (VDLD)(d 33) was 88% (74/84); the total CR rate after VDLD induction combined with cyclophosphamide+cytarabine+6-mercaptopurine (CAM) treatment (d80) was 94% (79/84); the recurrence rate was 24% (20/84). Among the 20 recurrent cases, there were 13 cases (65%) with ultra-early recurrence (within 18 months after diagnosis), 6 cases (30%) with early recurrence (18 to 36 months after diagnosis); 1 patient (5%) with late recurrence (over 36 months after diagnosis). During the follow-up period, twenty-eight children (33%) died (22 cases with recurrence or suspending treatment without remission, 2 cases with infection, 1 case of sudden death in chemotherapy, 1 patient failed in transplantation, 1 patient with severe cirrhosis, and 1 patient with unknown cause). (3) Kaplan-Meier analysis: the 5-year OS and EFS of the 84 children were (63±6)% and (60±6)% respectively. (4) Efficacy in different risk groups: prednisone sensitivity rates in the two different risk groups were 100% (34/34) and 26% (13/50), respectively (χ2=3.237, P<0.05). The CR rates at the end of VDLD induction therapy (d 33) were 100% (34/34) and 80% (40/50), respectively (χ2=2.767, P<0.05). The recurrence rate of children in the two groups was 12% (4/34) and 32% (16/50), respectively (χ2=4.245, P<0.05).The mortality rates of the two groups were 21% (7/34) and 42% (21/50), respectively (χ2=3.198, P<0.05). Kaplan-Meier analysis showed that the 5-year OS of the two groups were (77±7)% and (53±8)%; and the 5-year EFS of the two groups were (75±8)% and (49±8)% (χ2=4.235, 3.875, both P<0.05) . (5) COX multivariate regression analysis showed that the classification of risk according to CCLG-ALL 2008 was an important factor influencing the prognosis of children with T-ALL (OR=3.313, 95% CI 1.165-9.422, P=0.025).@*Conclusions@#The results of the risk group treatment according to the CCLG-ALL 2008 protocol showed that the long-term survival of children with middle risk was significantly better than that of children at high risk.

The treatment effect of Chlamydia trachomatis urogenital infection from 2006 to 2010 in Tianjin / 中华传染病杂志

Objective To investigate the efficacy of widely used antibiotics for urogenital Chlamydia trachomatis infection in recent 5 years.Methods A total of 2 809 cases of Chlamydia trachomatis urogenital infected patients who visited STD clinics of Tianjin Medical University General Hospital from 2006 to 2010 were collected.All the patients had accomplished a course of treatment of azithromycin, minocycline, moxifloxacin or clarithromycin and followed up for 3 months (once every month).Cochran-Armitage trend test was used to analyzed the antibiotics effect changing trends overtime.Results From 2006 to 2010, the etiology clearance rates of azithromycin were 76.70% (79/103), 74.19% (92/124), 74.13% (106/143), 71.43% (100/140) and 70.77% (92/130), respectively;those of minocycline were 75.31% (61/81), 64.67% (97/150), 66.53% (159/239), 65.05% (188/289) and 63.03% (104/165), respectively;those of moxifloxacin were 88.82% (167/188), 86.23% (119/138), 82.96% (185/223), 81.19% (233/287) and 81.03% (158/37), respectively;those of clarithromycin were 82.93% (34/41), 80.49% (33/41), 79.25% (42/53), 78.18% (43/55) and 75.00% (18/24), respectively.Ochran-Armitage trend test showed that antimicrobial efficacy of moxifloxacin for urogenital Chlamydia trachomatis infection rates declined year by year (P0.05).Conclusions The etiology clearance rate of moxifloxacin is the highest but gradually declines by years, and that of azithromycin takes the second place, while the treatment efficacy of minocycline is lower but quite stable.The number of cases treated with clarithromycin is too small to draw a conclusion.

Heterogeneity and clonal evolution in pediatric ETV6-RUNX1+ acute lymphoblastic leukemia by quantitative multigene fluorescence in situ hybridization / 中华血液学杂志

Objective@#To evaluate heterogeneity and clonal evolution in pediatric ETV6-RUNX1+ acute lymphoblastic leukemia (ALL) in China.@*Methods@#Totally 48 children (<14 years) with newly diagnosed ETV6-RUNX1+ ALL in Institute of Hematology and Blood Disease Hospital, CAMS and PUMC, from February 2006 to June 2011 were included. The copy number variations were analyzed by quantitative multigene fluorescence in situ hybridization (QM-FISH) in 48 patients. Non-normal distribution of measurement data were shown with Median (range) , count data were shown with percent (%) . Overall survival and event-free survival were estimated by the Kaplan-Meier method and compared with the log-rank test.@*Results@#Forty-eight patients were tested by QM-FISH. Of 48 patients, 70.8% harbored one clone, 18.8% two subclones, and 10.4% three or more subclones. The clone heterogeneity was detected by two different models: the linear succession model and the branching evolution model. ETV6-RUNX1+ ALL relapse evolved from an ancestral clone or a new clone. The patients relapsed from a new clone got the worse outcome.@*Conclusion@#The clone evolution was detected in pediatric ETV6-RUNX1+ ALL in China. QM-FISH might be helpful to evaluate the outcome of relapsed patients. A new clone was associated with a poorer outcome.

Significance of ikaros family zinc finger 1 deletion in pediatric B-acute lymphoblastic leukemia without reproducible cytogenetic abnormalities / 中华儿科杂志

<p><b>OBJECTIVE</b>To identify ikaros family zinc finger1 (IKZF1) deletion in patients with pediatric B cells-acute lymphoblastic leukemia (B-ALL) without reproducible chromosomal abnomalities and further investigate its value in this part of patients' pathogenesis and prognosis.</p><p><b>METHOD</b>The study was approved by the institutional review board of the authors' hospital and informed consent was obtained from the patients and/or their legal guardians. Data of 96 children with B-ALL patients without reproducible cytogenetic abnormalities whose bone marrows specimens were enough for DNA extraction for the detection were retrospectively selected. All the patients were diagnosed and systematically treated according to CCLG-ALL2008 in our hospital from April 2008 to April 2013. The 96 patients were divided into two groups according to the result of IKZF1's detection by multiplex ligation-dependent probe amplification (MLPA): The cases that with any of eight exons of IKZF1 deleted were entered into"Group with IKZF1 deletion"otherwise entered"Group without IKZF1 deletion". Disease free survival (DFS), event-free survival (EFS) and overall survival (OS) were compared between the two groups.</p><p><b>RESULT</b>Nineteen out of 96 B-ALL patients without reproducible cytogenetic abnormalities had IKZF1 deletion (20%). Three of 19 patients with IKZF1 deletions of the whole gene; ten of 19 patients with IKZF1 deletions of exon 1; 4 of 19 patients with IKZF1 deletions of exons 4-7; one of 19 patients with IKZF1 deletions of exons 2-7 and one of 19 patients with IKZF1 deletions of exons 1-6. Whose white blood cell (WBC) ≥ 50 × 10(9)/L inIKZF1 diletion group was more than whthout IKZF1 deletion group(42% vs. 13%, P=0.004). Patients with IKZF1 deletions had a lower 3-year DFS (0.67 ± 0.13 vs. 0.93 ± 0.04, P=0.001); EFS (0.67 ± 0.13 vs. 0.90 ± 0.04, P = 0.012) and OS(0.79 ± 0.09 vs. 0.96 ± 0.02, P=0.010) compared to those without IKZF1 deletions. Excluding the influence of sex, age, WBC count at diagnosis, cerebrospinal fluid state and prednisone response IKZF1 deletion still affected the patients' DFS, EFS and OS ( P<0.05 for all comparisons).</p><p><b>CONCLUSION</b>Some of pediatric B-cell precursor ALL without reproducible cytogenetic abnormalities had been detected to have IKZF1 deletion; IKZF1 deletion is an independent poor prognostic factor in these patients.</p>

Copy number variations in pediatric ETV6/RUNX1 positive acute lymphoblastic leukemia / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the copy number variations (CNVs) in pediatric ETV6/RUNX1 gene positive acute lymphoblastic leukemia(ALL) and its correlation with clinical features and prognosis.</p><p><b>METHOD</b>Totally 141 children (<14 years of age) with newly diagnosed ETV6/RUNX1 positive ALL in Institute of Hematology and Blood Diseases Hospital, were included from January 2006 to November 2012. The CNVs were analyzed by multiplex ligation-dependent probe amplification (MLPA). The survival rate between the patients with CNVs were explored. Overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method and compared with the log-rank test.</p><p><b>RESULT</b>Among the 141 cases, 55.3% (n=78) were boys and 44.7% (n=63) were girls and the median age was 4 (1-13) years. The estimated 5-year DFS rate for the patients was (84±4)%. The estimated 5-year OS rate for the patients was (85±4)%. Ninety-five patients were tested MLPA. CNVs were detected in 73 cases (76.8%). CNVs of genes EBF1(15.8%), CDKN2A/2B(18.9%), PAX5(21.1%), ETV6(54.8%), BTG1(10.5%) were detected in more than 10% of the patients. Among the 95 patients, EBF1 deletions were found in 9 patients and EBF1 amplifications were found in 6 patients; 5-year recurrence-free survival (RFS) was statistically significant among 3 groups (χ(2)=9.809, P=0.007) . PAX5 deletions were found in 13 patients and PAX5 amplifications were found in 7 patients; the difference in 5-year RFS was statistically significant between 3 groups(χ(2)=7.622, P=0.022). ETV6 deletions were found in 39 patients and ETV6 amplifications were found in 13 patients; the difference in 5-year RFS was statistically significant among the 3 groups (χ(2)=11.045, P=0.004).</p><p><b>CONCLUSION</b>The CNVs had prognostic relevance in ETV6/RUNX1 positive ALL.</p>

Treatment outcome of childhood standard-risk and median-risk acute lymphoblastic leukemia with CCLG-2008 protocol / 中华儿科杂志

<p><b>OBJECTIVE</b>To estimate the significance of the adjustment of acute lymphoblastic leukemia (ALL) risk group by monitoring minimal residual disease(MRD).</p><p><b>METHOD</b>Totally 285 children ALL patients who were diagnosed and systematically treated according to CCLG-2008 in Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC, from April 2008 to August 2011 were prospectively selected. Among these cases, 62.8% (n = 179) were boys and 37.2% (n = 106) were girls and the median age was 5.3(0.5-14.0). The patients who were at high-risk group initially were excluded. The grouping of cases: the patients were divided into two groups according to the dates of initial diagnosis. Group I had 126 patients who were initially diagnosed between April 2008 and December 2009 in whom therapeutic regimen was not adjusted by reassignment of risk group by MRD. Group II had 159 patients who were initially diagnosed between January 2010 and August 2011 whose therapeutic regimen was adjusted by reassignment of risk group by MRD at specific time (33rd day of induction chemotherapy and 12 weeks after the beginning of chemotherapy). MP-FCM Coulter FC-500 was used in the detection of MRD.</p><p><b>RESULT</b>Among these 285 patients, 94.0% (n = 268) were diagnosed as B-lineage acute lymphoblastic leukemia and 6.0% (n = 17) were T-lineage acute lymphoblastic leukemia. In group I, 61.9% (n = 78) patients belonged to low-risk group, 38.1% (n = 48) median-risk; in group II, before the adjustment, the rates of the low-risk group and median-risk group were 68.6% (n = 109) and 31.4% (n = 50) , respectively, while after the adjustment they were altered to 53.5% (n = 85) and 39.6% (n = 63) , furthermore 6.9% (n = 11) patients went into the high-risk group. Both groups were followed up for 2.5 years after their diagnoses, the disease of 7.4% (n = 21) patients relapsed, and the rates of two groups were 12.7% (n = 16) and 3.1% (n = 5) respectively, P = 0.009. The rate of serious infection (such as sepsis, pulmonary infection) of all these patients was 32.3% (92/285) , there was no significant difference between the two groups [28.6% (36/126) vs.35.2% (56/159) , P = 0.392]. The mortality of all these patients was 6.7% (19/285) , and that of group I was higher than that of group II [10.3% (13/126) vs. 3.8% (6/159) , P = 0.044]. The 2.5 years overall survival (OS), event-free survival (EFS) and disease-free survival (DFS) of group I were all lower than those of group II in Kaplan-Meier survivorship analysis (all P < 0.05). The two groups were followed up for 2.5 years after their diagnoses, after elimination of the confounding influence of sex, age, FAB subtype, WBC count, ratio of blast cells in bone marrow at diagnosed, chromosome karyotype and fusion gene, reassignment of risk group by MRD was used to calculate the OS, EFS and DFS of ALL patients (all P < 0.05). After the adjustment the risk group was more significant in the assessment of prognosis.</p><p><b>CONCLUSION</b>The reassignment of risk group in low and median risk groups children with acute lymphoblastic leukemia by MRD did not increase the rate of serious infection but could reduce the relapse rate and mortality, and was beneficial to increase the patients' OS, EFS and DFS.</p>

Immunosuppressive therapy using antithymocyte globulin and cyclosporin A with or without human granulocyte colony-stimulating factor in children with acquired severe aplastic anemia / 中华儿科杂志

<p><b>OBJECTIVE</b>To compare the efficacy and safety of four different regimens for pediatric severe aplastic anemia (SAA) with immuno-suppressive therapy (IST) with or without combined human granulocyte colony-stimulating factor (G-CSF).</p><p><b>METHOD</b>The authors retrospectively analyzed 105 children with SAA treated with IST with or without G-CSF in the hospital from February 2000 to September 2010. Regimen A, without G-CSF in the whole treatment, was used to treat Group A patients, n = 27; Regimen B, G-CSF, was initiated in Group B, n = 24, before the IST until hematologic recovery; Regimen C, G-CSF, was used together with the IST for Group C patients, n = 24, until hematologic recovery; Regimen D,G-CSF was used for Group D, n = 30, after the end of IST until hematologic recovery. The response rate, relapse rate, mortality, infection rate, infection-related death rate, risk of evolving into MDS/AML, survival rate, factors affecting the time of event-free survival and so on.</p><p><b>RESULT</b>(1) The response (CR+PR) rates 4, 6, 12 and 24 months after IST of the whole series of 105 SAA children were 50.5% (7.6%+42.9%) , 60.0% (21.9%+38.1%) , 67.6% (38.1%+29.5%) and 69.5% (40.0%+29.5%) respectively. The 2-year survival rate was 90.5%; the follow-up of the patients for 13 years showed that the whole survival rate was 87.6%. (2) The differences of the response rates 4, 6, 12 and 24 months after IST of the 4 groups were not significant (P > 0.05). (3) No significant differences were found in the mortalities 4, 6, 12 and 24 months among the 4 groups (P > 0.05). (4) Of the 105 patients, 4 children had relapsed disease in the period of time from 6 to 24 months after IST. All the four patients belonged to the groups with G-CSF. (5) The use of G-CSF could not decrease the infection period before IST (day) (P = 0.273), and it had no impact on the infection rate after IST (P = 0.066). It did not reduce the rates of septicemia and infectious shock. And to the infection-related death rate no significant conclusion can be made. (6) Follow up of the patients for 13 years, showed that 2 had the evolution to MDS/AML in the 105 patients and the two children belonged to the groups with G-CSF. (7) Kaplan-meier curve analysis did not show any differences in the survival rates of the four groups. (8) Cox regression analysis showed that the use of G-CSF had no benefit to the patients' long term survival. While the age of diagnosis and the infection history before IST were significantly related to the patients' long term survival.</p><p><b>CONCLUSION</b>The use of G-CSF did not contribute to the early response and could not reduce the infection rate, infection-related death rate and the patients' long term survival. There were no significant differences in the survival rates of the four groups. Attention should be paid to the risk of the evolution to MDS/AML.</p>

Efficacy observation of polyethylene glycol conjugated asparaginase for induction treatment of children with newly diagnosed acute lymphoblastic leukemia / 中华儿科杂志

<p><b>OBJECTIVE</b>To observe the efficacy of polyethylene glycol conjugated asparaginase (peg-asp) for induction treatment of children with newly diagnosed acute lymphoblastic leukemia (ALL).</p><p><b>METHOD</b>A total of 268 newly diagnosed children with ALL enrolled in CCLG-2008 from January, 2010 to August, 2012 were analyzed. Patients received either native Escherichia coli asparaginase or pegaspargase along with multiagent chemotherapy during remission induction treatment. Status of bone marrow aspiration was assessed on day 15, day 33 (M1, M2, M3).</p><p><b>RESULT</b>Of the 268 patients stratified, 37.3% (n = 100) were SR, 32.1% (n = 86) were IR, and 31.6% (n = 82) were HR; 159 patients received native Escherichia coli asparaginase and 109 patients received pegaspargase. Characteristics of two groups in age, sex, blood count at diagnosis, immunophenotype and response to prednisolone had no significant difference (P > 0.05). Bone marrow status on day 15 in pegaspargase group was M1 in 70 (64.2%) cases, M2 in 23 (21.1%) and M3 in 16 (14.7%), while in native Escherichia coli asparaginase group, M1 in 112 (70.4%) cases, M2 in 21 (13.2%) and M3 in 26 (16.4%), respectively (χ(2) = 2.938, P = 0.230). Bone marrow status on day 33 was M1 in 105 (96.3%), M2 in 3 (2.8%) and M3 in 1 (0.9%) in pegaspargase group, while it was M1 in 154 (96.9%) cases, M2 in 5 (3.1%) and M3 in native Escherichia coli asparaginase group, respectively (χ(2) = 1.494, P = 0.474).</p><p><b>CONCLUSION</b>Domestic pegaspargase of our country can achieve the similar efficacy in induction treatment for ALL patients as compared with native Escherichia coli asparaginase. The drug could be considered as not only the choice for allergic patients but also a first-line alternative for new patients.</p>

NPM1 and CEBPA mutations in pediatric cytogenetically normal acute myeloid leukemia / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the frequency of the nucleophosmin (NPM1) gene and the CCAAT/enhancer binding protein α gene (CEBPA) through polymerase chain reaction (PCR) array in pediatric patients with cytogenetically normal acute myeloid leukemia (CN-AML) and explore the clinical significances of these mutations.</p><p><b>METHOD</b>Between August 2009 and December 2012, 30 children (<16 years old) with newly diagnosed CN-AML were included. The clinical characteristics were analyzed in these patients. PCR combined with direct sequencing was used to detect NPM1, CEBPA gene mutations. All the data were statistically analyzed using SPSS17.0 software.</p><p><b>RESULT</b>The gene mutations were detected in each of the 30 patients. NPM1 mutation was positive in three patients (10%) with type A mutation, while CEBPA mutation was positive in two patients (6.7%) with double mutations (TAD, bZIP) . Besides, FLT3/ITD mutation was positive in three patients. Patients with NPM1 or FLT3/ITD had a significantly elevated diagnostic WBC count with a median diagnostic WBC count of 102.80×10(9)/L compared with 18.56×10(9)/L for the patients without mutations(t = 2.353, P = 0.043), as well as the marrow blast percentage (94.0% vs. 80.0%, t = 3.804, P = 0.002). The complete remission was achieved in all the 3 patients with NPM1 mutations and 2 patients with CEBPA mutations. All the patients with these mutations also achieved 2-year event-free survival (EFS) and 2-year overall survival (OS), while 2-year EFS and 2-year OS of the other patients were (40.1 ± 11.2)% and (51.8 ± 10.9)% (P = 0.044, 0.091, respectively).</p><p><b>CONCLUSION</b>NPM1 and CEBPA mutations may indicate a favorable prognosis in pediatric CN-AML.</p>

Outcomes of treatment of Chlamydia trachomatis infection with azithromycin: an evaluation by different criteria / 中华皮肤科杂志

ObjectiveTo compare the recovery rates calculated according to different criteriain patients with urogenital Chlamydia trachomatis (Ct) infection after treatment with azithromycin. Methods Clinical data on outpatients who were diagnosed with urogenital Ct infection and treated with azithromycin in the sexually transmitted disease(STD) outpatient clinic of Tianjin Medical University General Hospital were retrospectively reviewed. Recovery rates were calculated according to the improvement of symptom and (or) reexamination results of Ct at 1,5 and 9 weeks after the end of treatment.ResultsSignificant differences were observed between the recovery rates calculated according to symptom improvement and those according to laboratory reexamination results.No obvious correlation existed between the presence of symptom and positive reexamination results.The recovery rates calculated according to the second reexamination result differed significantly from those according to the first reexamination result,but were similar to those according to the third reexamination result. ConclusionsThe cure of Ct infection should be determined according to laboratory test results,and two times of reexamination at 1 and 5 weeks after the final treatment are recommended.

Polymorphism of HLA-D QA1 alleles in Chinese Han patients with persistent Chlamydia trachomatis genital infection / 中华皮肤科杂志

ObjectiveTo analyze the association of HLA-DQA1 gene polymorphism with persistent Chlamydia trachomatis genital infection.Methods Blood samples were collected from 80 patients with persistent genital Chlamydial infection,80 patients with common genital Chlamydial infection(who tested negative for Chlamydia trachomatis after one course of standard systemic treatment) and 80 normal human controls.HLA-DQA1 alleles were genotyped by PCR followed by gene sequencing.ResultsThe frequency of HLA-DQA1*0102 allele and HLA-DQA1*0501 allele was 22.5％ and 5.0％ respectively in patients with persistent genital Chlamydial infection,5％ and 20％ respectively in those with common genital Chlamydial infection,2.5％ and 17.5％ respectively in normal human controls.Compared with the patients with common genital Chlamydial infection and controls,the patients with persistent genital Chlamydial infection had a higher frequency of HLA-DQA1*0102(x2 =14.6286,P ＜ 0.001 ),but a lower frequency of DQA1*0501 (x2 =6.2598,P ＜ 0.05).ConclusionsHLA-DQA1*0102 allele may be a susceptible gene or closely linked with the susceptible genes of persistent genital Chlamydial infection.HLA-DQA1*0501 allele may have protective effects against persistent genital Chlamydial infection.

Effects of neural stem cell transplantation on hippocampus synaptophysin expression and learning memory abilities of Alzheimer disease rats / 中国组织工程研究

BACKGROUND:Previous studies have demonstrated that transplanted neural stem cells can survive and proliferate in the brain of Alzheimer disease(AD)rats,however,it is poorly understood whether it can rebuild the nerve tracts by substituting the injured or dead neurons and improve learning and memory abilities.Synaptophysin is one of the important markers of synaptic rebuilding.OBJECTIVE:To observe the effects of neural stem cell transplantation on synaptophysin expression in hippocampus and learning and memory abilities of AD rats.METHODS:Sprague Dawley rats were randomly divided into the normal control,AD model,2-week-transplantation and 4-week-transplantation groups.All rats were established AD models except that in the normal control group.Neural stem cells were isolated from the dentate gyrus of hippocampus of newborn rats,labeled with Hoechst33258,and then transplanted into CA1 region of hippocampus of rats in the 2-week-transplantation and 4-week-transplantation groups.The behavioral testing in the rats was performed using Y-maze trial.Nissl staining and synaptophysin immunohistochemistry were detected after the rats were sacrificed.The same volume of stroke-physiological saline solution was injected into rats in the AD models group using the identical methods.There was no treatment in the normal control group.RESULTS AND CONCLUSION:①The cells number in the hippocampal CA1 region of the 2-week-transplantation and 4-week-transplantation groups were increased than that of AD model group,but were still less than that of the normal control group(P ＜ 0.05).There was no significantly difference between the absorbance values of 2-or 4-week-transplantation group and control group(P ＞ 0.05).②The absorbance values of the 2-week-transplantation and 4-week-transplantation were significantly greater than that of the control and AD model groups(P ＜ 0.05).③The learning and memory abilities in 2-and 4-week-transplantation group enhanced obviously and their correct reaction rates improved evidently,which was found statistically significant difference from AD model group(P ＜ 0.05),while no statistically significant difference from control group(P ＞ 0.05).The transplanted neural stem cells may promote the synaptic rebuilding and improve learning and memory abilities in AD rats.

Gene expression of transforming growth factor beta-1 in tendon healing / 中国组织工程研究

BACKGROUND: We have paid more attention on the effects of growth factors on tendon healing and adhesion formation, especially on the correlation of transforming growth factor with tissue adhesion and scar formation. OBJECTIVE: To investigate the expression of transforming growth factor beta-1 mRNA in the zone Ⅱ flexor tendon of wound-healing rabbit models. DESIGN: Randomized controlled animal study. SETTING: Department of Orthopaedics, Affiliated Hospital of Medical College, Qingdao University. MATERIALS: Sixty clean adult New Zealand white rabbits weighting 4.0-4.5 kg, of either sex, were provided by Qingdao Animal Experimental Center. Left forelimbs of each animal were as experimental side, and right forelimbs of each animal were as control. There were 6 time points, namely at days 1, 7, 14, 21, 28 and 56, 10 rabbits in each time point. Of the 10 rabbits, 6 rabbits received the in situ hybridization and 4 rabbits received the immunohistochemical staining. Animal intervention met the animal ethical standard. METHODS: Experiments were performed at the Animal Experimental Center of Hospital Affiliated to Medical College of Qingdao University from September 2005 to July 2006. After anesthesia, each rabbit underwent complete transection of the profundus middle flexor tendon in zone Ⅱ, and then the tendon was repaired by the Kessler method. Rabbits in the control group did not receive any intervention. Rabbits were anesthetized and killed 1, 7, 14, 21, 28 and 56 days after the surgery. Skin was incised along the original incision at the experimental sides to obtain tendons and tendon sheaths. The same measurements were performed in the control group. MAIN OUTCOME MEASURES: Tenocytes and tendon sheath cells were detected with the in situ hybridization and the immunohistochemical staining to observe the expression of transforming growth factor beta-1. RESULTS: Sixty rabbits were involved in the result analysis. ①The in situ hybridization results: Expression of transforming growth factor beta-1 mRNA was increased at day 1 after tendon injury in the experimental group, reached a peak at days 14-21 after tendon injury, reduced at day 28 and was still in a high level at day 56. Expression of transforming growth factor beta-1 mRNA was high in tendon sheath cells around the repaired region. At the same time point, the expression of transforming growth factor beta-1 mRNA was higher in tendon sheath cells than in tenocytes. Low expression of transforming growth factor beta-1 mRNA was found in tenocytes and tendon sheath cells in the control group. The expression of transforming growth factor beta-1 mRNA in tenocytes and tendon sheath cells was higher in the experimental group than in the control group at each time point (P ＜ 0.05). ②Immunohistochemical staining results: Expression of transforming growth factor beta-1 protein was elevated at day 1 after the surgery, reached the peak at days 14-21 and was still in a high level at day 56 in the experimental group. Low expression of transforming growth factor beta-1 protein was seen in the control group. CONCLUSION: The normal uninjured tenocytes and tendon sheath cells produce transforming growth factor beta-1. The cytokine is activated in the injured tendon. The increase of this cytokine in both tenocytes and tendon sheath fibroblasts are coincidence with both extrinsic and intrinsic mechanisms for tendon repair.

Apoptosis in hippocampal neurons and change of mitogen-activated protein kinases expression in rats with sleep deprivation / 中国组织工程研究

BACKGROUND: Mitogen-activated protein kinases (MAPKs) is a group of protein kinase related with neuronal apoptosis. Sleep derivation can lead to neuronal apoptosis.OBJECTIVE: To observe change and possible significance of MAPKs in rats after sleep deprivation.DESIGN: Prospective study with complete randomization.SETTING:Research Room of Nerve, Department of Physiology, Zhengzhou University.MATERIALS: The experiment was performed at Zhengzhou University from June 2000 to October 2002. Totally 24 adult healthy SD rats were selected.METHODS: A total of 24 rats were randomly assigned into rapid eye movement (REM) sleep deprivation group, REM sleep deprivation control group and normal control group with 8 rats in each group. The rats in the sleep deprivation group received successive sleep deprivationfor 72 hours from 8:00in the morning. The rats in the normal control group were fed in the rearing cage, having normal sleep-awareness cycle. Their morphological change was observed. Another 24 rats were grouped as above and determined with MAPKs. Morphological change of neurons in hippocampus of rats after sleep deprivation was observed with terminal dUTP nick end-labelling (TUNEL)staining. Changes of activity of extracellular signal-regulated kinase (ERK)and expression of c-Jun N-terminal kinase (JNK) were observed.MAIN OUTCOME MEASURES: ①Morphological change of hippocampal neuron in rats after sleep derivation was observed. ②Changes of expressions of ERK and JNK in hippocampal neuron were observed.RESULTS: ①Morphological change of hippocarnpal neuron: A mass of apoptotic positive cells appeared in CA1 and CA3 regions of rats in the REM sleep deprivation group, mainly distributed in pyramidal layer of hippocampus. A few apoptotic cells appeared in CA2 region. Seldom apoptotic cells appeared in the CA4 region. There was no significant positive cell in hippocampal tissue sections of the normal control group and REM sleep deprivation control group. ②Change of ERK activity: It was significantly lower in the REM sleep deprivation group than the REM sleep deprivation control group and normal control group (1 764.00±941.56,6 139.67±2 863.62,566.700±2 763.41 ,t=3.211 1,0.986 3,P ＜ 0.05). ③JNK positive expression: It was markedly higher in the REM sleep deprivation group than the REM sleep deprivation control group and normal control group (87.5%, 25%, 75%, t=3.412 1, P＜0.05).CONCLUSION: The sleep deprivation can cause change of MAPKs activity, which may be related with neuron apoptosis.

The effect of selective estrogen receptor modulator,raloxifene on the gene expression of endothelin-1 in vascular endothelial cells and the relationship with estrogen receptor / 中华老年医学杂志

Objective To investigate the effect of raloxifene on the mRNA expression of endothelin-1 in vascular endothelial cells and assess the role of estrogen receptor. Methods Bovine carotid endothelial cells were pretreated with 10nM raloxifene for 24 hours, then total RNA was harvested and Northern blotting was performed to investigate the effect of raloxifene on the mRNA expression of endothelin-1. Furthermore, estrogen receptor inhibitor, 100nM ICI 182 780 was used to pretreat the cells together with raloxifene and the expression of endothelin-1 was observed too. Results The mRNA expression of endothelin-1 in bovine carotid endothelial cells was inhibited significantly by pretreatment with raloxifene and this effect could be blocked by ICI182 780 (0.16?0.05 vs 0.39?0.07, P

Changes of MAPKs expression in rat hippocampal neurons after sleep deprivation / 中国病理生理杂志

AIM: To explore the change and the possible role of MAPKs in rat hippocampus neuron after sleep deprivation. METHODS: The morphology of hippocampus neuron after sleep derivation was observed by TUNEL and HE staining, the activity of ERK was assayed by ?-liquid scintillation counting and the expression of JNK was detected by Western blot. RESULTS: In paradoxical sleep deprivation (PSD) group, the number of apoptotic cells in hippocampus was increased. The scores of ERK activity were (1 764.00)?941.56. Compared with control groups, the ERK activity was obviously decreased (P

Identification of Cornu Cervi Pantotrichum by X-ray diffraction fourier fingerprint pattern / 中成药

AIM:To develop a new identification and analyfical method for Cornu Cervi Pantotrichum . METHODS: Powder X ray diffraction Fourier fingerprint pattern was adopted. RESULTS: The reference X ray diffraction Fourier fingerprint pattern and characteristic diffraction peaks of Cornu Cervi Pantotrichum were obtained by three samples of Cornu Cervi Pantotrichum and one sample of Cornu Cervi Pantotrichum . CONCLUSION: This method can be used for identification of Cornu Cervi Pantotrichum .

Identification on pheretima by X-Ray diffraction Fourier pattern method / 中成药

Objective: To develop a new identification and analysis method of crude drug Pheretima . Method: Powders of pheretima were identified by means of X ray differacion Fourier pattern. Results: Experiments and analysis were carried out on five samples of pheretima. The standard X ray diffraction Fourier pattern and characteristic diffraction peaks of Pheretima were obtained.Conclusion: This method can be used for identification on crude drug Pheretima .