[Influencing factors of futile recanalization after endovascular therapy in acute ischemic stroke patients with large vessel occlusions].

Objective: To analyze the influencing factors of futile recanalization after endovascular therapy (EVT) in acute ischemic stroke patients with large vessel occlusions (AIS-LVO). Methods: AIS-LVO patients who underwent EVT with successful recanalization between January 2019 and December 2021 in Neurovascular Center of Changhai Hospital of Naval Medical University were retrospectively selected. Modified Rankin scale (mRS) score 3 months after EVT was used as the prognostic evaluation index, and patients with mRS scores≤2 were classified as the meaningful recanalization group and mRS scores 3-6 as the futile recanalization group. The risk factors, National Institutes of Health stroke scale (NIHSS) score, Glasgow coma scale (GCS) score, Alberta Stroke Program Early CT (ASPECT) score, core infarct volume, etc. in both groups were analyzed, and the influencing factors of futile recanalization after EVT were analyzed by multivariate logistic regression. Continuous variables that do not conform to the normal distribution are represented by [M(Q1,Q3)]. Results: A total of 368 patients meeting the inclusion criteria were collected, including 228 males and 140 females, and aged 68 (61, 77) years. There are 196 patients and 172 patients in the meaningful recanalization and futile recanalization groups, respectively, with the rate of futile recanalization 3 months after EVT of 46.74% (172/368). Comparing the general information and risk factors between the two groups found that the age of patients in the futile recanalization group [71 (65, 79) years] was higher than that in the meaningful recanalization group [65 (59, 72) years]. The baseline NIHSS score [18 (14, 22)] and the rate of not achieving modified Thrombolysis in Cerebral Ischemia grade 3 (mTICI 3) reperfusion (36.1%) were higher in the futile recanalization group than those in the meaningful recanalization group [12 (7, 17) and 19.9%]. The baseline GCS score [11 (9, 13)] was lower in the futile recanalization group than that in the meaningful recanalization group [14 (11, 15)]. The core infarct volume in the futile recanalization group [28 (7, 65) ml] was larger than that in the meaningful recanalization group [6 (0, 17) ml]. The ASPECT score [7 (5, 9)] was lower in the futile recanalization group than that in the meaningful recanalization group [9 (7, 10)]. In addition, the proportion of hypertension, atrial fibrillation, general anesthesia, and symptomatic intracranial hemorrhage was higher in the futile recanalization group (all P<0.05). The time from symptom onset to puncture and from symptom onset to reperfusion was longer in the futile recanalization group (both P<0.05). There were statistically significant differences in trial of Org 10172 in acute stroke treatment (TOAST) classification and the site of occluded blood vessels between the two groups (both P<0.05). Multivariate logistic regression indicated that age ≥80 years(OR=1.935,95%CI: 1.168-3.205), baseline NIHSS score (OR=1.999,95%CI: 1.202-3.325), GCS score (OR=2.299,95%CI: 1.386-3.814), previous stroke history (OR=1.977,95%CI: 1.085-3.604), general anesthesia (OR=1.981,95%CI: 1.143-3.435), not achieving grade 3 recanalization (OR=2.846, 95%CI: 1.575-5.143), ASPECT score<6 (OR=2.616, 95%CI: 1.168-5.857), and core infarct volume>70 ml (OR=2.712, 95%CI: 1.130-6.505) were risk factors for futile recanalization. Conclusion: Age≥80 years, previous stroke history, baseline NIHSS score≥20, GCS score≤8, general anesthesia, ASPECT score<6, core infarct volume>70 ml, and failure to achieve Grade 3 recanalization are independent influencing factors for futile recanalization after endovascular therapy in AIS-LVO patients.

[Evaluation of the right ventricular function in patients with pneumoconiosis by echocardiography].

Objective: To investigate right ventricular function in patients with pneumoconiosis, and to provide a basis for quantitative diagnosis and treatment of pneumoconiosis in clinical practice. Methods: A total of 43 patients with pneumoconiosis who were hospitalized consecutively in Shijiazhuang Prevention and Treatment Center for Occupational Diseases from May 2015 to May 2016 were enrolled, and according to the stage of pneumoconiosis, they were divided into stage I group with 16 patients, stage II group with 14 patients, and stage III group with 13 patients. A total of 16 healthy subjects were enrolled as control group. Echocardiography was performed and the relevant parameters were recorded, i.e., right ventricular transverse diameter (RVTD), tricuspid annular plane systolic excursion (TAPSE), and right ventricular myocardial performance index(Tei index). Results: There were significant differences in Tei index and TAPSE between all groups (P <0.05) except between the stage I group and the control group in terms of Tei index (P>0.05) and between the stage I group and the stage II group in terms of TAPSE (P>0.05). Right ventricular Tei index was negatively correlated with TAPSE (r=-0.547,P<0.05). Conclusion: A combination of right ventricular Tei index and TAPSE can be used for early quantitative evaluation of right ventricular function in patients with pneumoconiosis.

[Improved clinical outcome of acute myeloid leukemia with FLT3-ITD mutation treated with sorafenib].

OBJECTIVE: To analyze the efficacy of sorafenib on the treatment of patients diagnosed as acute myeloid leukemia(AML) with FLT3-ITD mutation. METHODS: From January 2012 to February 2015, 42 cases of AML with FLT3-ITD mutation according to MICM (morphology, immunology, cytogenetics and molecular) diagnosis system in our hospital were retrospectively analyzed. Thirty-two cases were refractory to chemotherapy or relapsed, who were treated with sorafenib or combined with chemotherapy. Ten patients relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), who were retreated with sorafenib or combined with donor lymphocyte infusion (DLI) or chemotherapy. In the first group, 13 of 32 patients accepted allo-HSCT. RESULTS: The overall response rate of all 42 patients was 73.8%, including 4 (9.5%) complete molecular remission (CMR), 9 (21.4%) complete remission (CR), 8 (19%) complete remission with incomplete hematologic recovery (CRi), 10 (23.8%) partial remission (PR), and 11 (26.2%) none remission (NR). The response rate of sorafenib alone for 17 patients was 70.6%, and that of sorafenib plus chemotherapy was 66.7% (P=0.555). Thirteen patients who received allo-HSCT included 6 CMR/CR/CRi, 4 PR, and 3 NR before transplant. The 2-year overall survival (OS) rate and progress free survival (PFS) rate in all patients were 36.9% and 28.7%, and the corresponding median time were 18 months and 9 months respectively. The 2-year OS rate in 23 patients who received sorafenib combined with allo-HSCT was superior to that in 19 patients not receiving allo-HSCT (45.5% vs 23.9%, P=0.041), so was PFS rate (44.0% vs 9.7%, P=0.014). Twelve cases died of disease progression, four of infection, and one of chronic graft versus host disease after transplant. CONCLUSIONS: Sorafenib combined with chemotherapy improves response rate of AML patients with FLT3-ITD mutation. Those who are treated with sorafenib plus allo-HSCT obtain better long-term survival.

Relationship between Leukopenia and Intercellular Adhesion Molecules in Graves' Disease.

OBJECTIVE: Changes in soluble intercellular adhesion molecule-1 (sICAM-1) and E-selectin levels as well as leukocyte count were examined in this study to explore the relationship between leukopenia and ICAMs in Graves' disease (GD). METHODS: Fasting blood samples were obtained from 37 GD patients with normal leukocytes and 32 GD patients with leukopenia. Enzyme-linked immunosorbent assay (ELISA) was performed to determine serum sICAM-1 and E-selectin levels for comparison. The same analyses were repeated for the GD patients with leukopenia after glucocorticoid treatment (15 mg/day to 30 mg/day prednisone). RESULTS: The ELISA results showed that E-selectin levels were higher in GD patients with leukopenia than those with normal leukocytes (p < 0.05), but these levels decreased after glucocorticoid (prednisone) treatment (p < 0.05). No significant change in sICAM-1 levels was observed (p = 0.12). Correlation analysis showed that leukocyte count and E-selectin were negatively correlated (r = -0.778; p < 0.05). CONCLUSION: E-selectin may have an important function in GD with leukopenia, and glucocorticoids (prednisone) could decrease E-selectin level, which may be a new therapy target for GD with leukopenia.

[Efficacy and safety of chimeric antigen receptor T-cell therapy followed by allogeneic hematopoietic stem cell transplantation in 21 patients with Ph-like acute lymphoblastic leukemia].

Objective: To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) . Methods: Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed. Results: Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients' autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0-2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively (P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions: CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.

Comparison of Aspiration versus Stent Retriever Thrombectomy as the Preferred Strategy for Patients with Acute Terminal Internal Carotid Artery Occlusion: A Propensity Score Matching Analysis.

BACKGROUND AND PURPOSE: There is no consensus on endovascular treatment for terminal ICA. The purpose of this study was to evaluate the comparative safety and efficacy of preferred aspiration thrombectomy and stent retriever thrombectomy for revascularization in patients with isolated terminal ICA occlusion. MATERIALS AND METHODS: We conducted a retrospective analysis of patients with terminal ICA occlusion treated with aspiration thrombectomy or stent retriever thrombectomy in our center, from September 2013 to November 2018. To minimize the case bias, propensity score matching was performed. The primary outcomes were successful reperfusion defined by expanded TICI grades 2b-3 at the end of all endovascular procedures and puncture-to-reperfusion time. RESULTS: A total of 109 consecutive patients with terminal ICA occlusion were divided into the aspiration thrombectomy group (40 patients) and the stent retriever thrombectomy group (69 patients), and 30 patients were included in each group after propensity score matching. The proportion of complete reperfusion was significantly higher in the aspiration thrombectomy group (OR 4.75 [95% CI, 1.10-1.38]; P = .002). The median puncture-to-reperfusion time in the aspiration thrombectomy group was shorter than that in the stent retriever thrombectomy group (38 versus 69 minutes; P = .001). Fewer intracerebral hemorrhage events were recorded in the aspiration thrombectomy group (OR 0.29 [95% CI, 0.09-0.90]; P = .028). No significant differences were observed for good outcomes (OR 1.92 [95% CI, 0.86-4.25]) and mortality (OR 0.84 [95% CI, 0.29-2.44]) at 90 days. CONCLUSIONS: For the treatment of terminal ICA occlusion, aspiration thrombectomy was technically superior to stent retriever thrombectomy in the absence of a balloon guide catheter in achieving successful reperfusion with shorter puncture-to-reperfusion time and procedure-related adverse events.

Epidemiologic and clinical characteristics of 91 hospitalized patients with COVID-19 in Zhejiang, China: a retrospective, multi-centre case series.

BACKGROUND: Recent studies have focused on initial clinical and epidemiological characteristics of the coronavirus disease 2019 (COVID-19), which is the mainly revealing situation in Wuhan, Hubei. AIM: This study aims to reveal more data on the epidemiological and clinical characteristics of COVID-19 patients outside of Wuhan, Zhejiang, China. DESIGN: This study was a retrospective case series. METHODS: Eighty-eight cases of laboratory-confirmed and three cases of clinically confirmed COVID-19 were admitted to five hospitals in Zhejiang province, China. Data were collected from 20 January 2020 to 11 February 2020. RESULTS AND DISCUSSION: Of all 91 patients, 88 (96.70%) were laboratory-confirmed COVID-19 with throat swab samples that tested positive for SARS-Cov-2, three (3.30%) cases were clinically diagnosed. The median age of the patients was 50 (36.5-57) years, and female accounted for 59.34%. In this sample, 40 (43.96%) patients had contracted the disease from local cases, 31 (34.07%) patients had been to Wuhan/Hubei, eight (8.79%) patients had contacted with people from Wuhan, and 11 (12.09%) patients were diagnosed after having flown together in the same flight with no passenger that could later be identified as the source of infection. In particular within the city of Ningbo, 60.52% cases can be traced back to an event held in a temple. The most common symptoms were fever (71.43%), cough (60.44%) and fatigue (43.96%). The median of incubation period was 6 (interquartile range 3-8) days and the median time from the first visit to a doctor to the confirmed diagnosis was 1 (1-2) days. According to the chest computed tomography scans, 67.03% cases had bilateral pneumonia. CONCLUSIONS: Social activity cluster, family cluster and flying alongside with persons already infected with COVID-19 were how people got infected with COVID-19 in Zhejiang.

Quantitative assay for Janus kinase 2 (JAK2) mutation in Chinese patients with chronic myeloproliferative disorders.

The Janus kinase 2 (JAK2) V617F mutation has considerably helped understanding of the molecular pathogenesis of chronic myeloproliferative disorders (MPD), hence this study investigated for the first time the mutational status and relative quantitation of JAK2 V617F mRNA in Chinese patients with chronic MPD. The study cohort comprised 123 chronic MPD patients (35 with polycythaemia vera [PV], 85 with essential thrombocythaemia [ET], three with idiopathic myelofibrosis [IMF]). Blood samples examined by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and capillary electrophoresis showed that the prevalence of the JAK2 V617F mutation was 100%, 62.4% and 66.7% in PV, ET and IMF patients, respectively. The proportion of JAK2 V617F mutated mRNA was 89.5% in homozygotes and 57.9% in heterozygotes; 18 PV heterozygous patients showed significantly higher mutated JAK2 mRNA levels than 36 heterozygous ET patients. Six of 93 patients exhibited abnormal karyotypes, but specific chromosomal abnormality was not found. The combination of ARMS-PCR and capillary electrophoresis enables quantitative assay of JAK2 V617F mutation, which helps in chronic MPD diagnosis and estimation of minimal residual disease.

Advanced malignant pleural or peritoneal effusion in patients treated with recombinant adenovirus p53 injection plus cisplatin.

The aim of this study was to evaluate the efficacy of recombinant adenovirus p53 agent (rAd-p53) injection combined with cisplatin (CDDP) for the treatment of malignant pleural or peritoneal effusion. After puncture drainage, patients in the treatment group (n = 27) received intracavitary administration of rAd-p53 (2 x 10(12) virus particles) once a week for 4 weeks. At 48 h after each rAd-p53 injection, patients were given intracavitary administration of cisplatin 60 mg/m(2). This administration procedure continued once a week for 4 weeks. The control group (n = 21) received the same intracavitary therapy as the treatment group but without rAd-p53 therapy. Efficacy was evaluated by clinical observations, computed tomography, tumour markers, Karnofsky score and short-term follow-up. The total effective rates for the treatment group (63.0%) were significantly higher than for the control group (42.9%), suggesting that the treatment group benefited over the control group. In conclusion, rAd-p53 therapy is a safe and effective treatment for advanced malignant pleural or peritoneal effusion.

[Clinical features and curative effect analysis of patients with myeloid neoplasms and RUNX1 mutations].

Objective: To investigate the survival and prognostic factors of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) for patients with myeloid neoplasms and RUNX1 mutations. Methods: From July 2014 to April 2018, the clinical data of forty-two AML/MDS patients with RUNX1 mutations in the First Affiliated Hospital of Soochow University were retrospectively analyzed. The clinical characteristic features and distribution of the mutations frequently observed with RUNX1 mutations were summarized, the prognosis of allo-HSCT for these patients was also analyzed. Results: Among 42 AML/MDS patients with RUNX1 mutations, 27 were male, 15 were female. The median age was 43.5 (16-68) years old. There are 31 patients in allo-HSCT group and 11 patients in chemotherapy group. RUNX1 mutations co-occurred with many other gene mutations, the most frequent mutations were FLT3 (26.2%, 11/42) . Interestingly, FLT3 mutations only occurred in AML patients compared with MDS patients (P=0.014) . ASXL1 (25%, 3/12) mutations were observed as the most frequent co-mutations in MDS patients. One-year overall survival (OS) , disease-free survival (DFS) of allo-HSCT and chemotherapy patients were (70.6±9.0) %, (61.0±9.4) % and (34.4±16.7) %, (22.4±15.3) %, respectively. When OS and DFS between allo-HSCT and chemotherapy patients were compared, significant differences (χ(2)=4.843, 4.320, P<0.05) were showed. In univariate analysis, transplant age >45 years was a negative effect for OS [HR=4.819 (95% CI 1.145-20.283) , P=0.032] and DFS [HR=5.945 (95% CI 1.715-20.604) , P=0.005]. Also, complex chromosome karyotype abnormality was a negative effect for OS [HR=5.572 (95%CI 1.104-28.113) , P=0.038]. Conclusion: Transplant age (>45 years) and complex chromosome karyotype abnormality were negative prognostic factors in allo-HSCT for myeloid neoplasms patients with RUNX1 mutations.

[Clinical significance of expressions of EVI1 and BRE genes in 47 acute leukemia patients with MLL rearrangement].

Objective: To investigate the overexpression frequencies of BRE and EVI1, the correlation between BRE and EVI1 expressions and their possible clinical implications in 11q23/MLL rearrangement acute leukemia. Methods: Cytogenetic examination of bone marrow cells was performed by short-term culture method. R-banding technique was used for karyotype analysis. 47 patients were detected by interphase fluorescence in situ hybridization (FISH) with dual-color break apart MLL probe. The expressions of EVI1 and BRE genes were detected by real time quantitative reverse transcription polymerase chain reaction (RQ-PCR) . The correlation and prognostic significance were statistically tested. Results: 11q23/MLL rearrangements were confirmed by karyotyping and FISH, respectively in 47 patients. According to immunophenotypic analyses of 37 patients, 5 patients showed positive for CD19, CD79a or CD10, 1 for CD7; the others for CD33, CD13, CD14 and CD15, and 16 of them for CD34. Of the 47 patients, 18 patients showed EVI1 overexpression and most of them presented with t (6;11) and M(4)/M(5). The EVI1 expression was high in t (6;11) or t (9;11) subgroup comparable with levels observed in normal subgroup (P=0.038, 0.022, respectively) . 15 patients showed high BRE expression, and most of them presented with t (9;11) and M(4)/M(5). High BRE expression was found in t (4;11) , t (6;11) , t (9;11) and t (11;19) subgroups, respectively by comparing with normal subgroup. The BRE expression was higher in t (4;11) (P=0.004) or t (9;11) (P=0.012) subgroup than in t (6;11) subgroup. Patients with EVI1 overexpression had a short survival compared with those with low EVI1 expression (P=0.049) and it also did in t (9;11) subgroup (P=0.024) . Patients with t (9;11) and high BRE expression had a long survival compared with those with t (9;11) and low BRE expression (P=0.024) . Conclusion: The EVI1 overexpression was significantly frequent in acute leukemia patients with 11q23/MLL rearranged, especially within t (6;11) subgroup and M(4)/M(5), which was associated with an inferior outcome. High BRE expression was observed frequently in 11q23/MLL-rearranged acute leukemia especially within t (9;11) subgroup and M(5).

[Critical roles of matrix metalloproteinases secreted by leukemic cells in the pathogenesis of central nervous system leukemia].

Objective: To observe the effects of matrix metalloproteinases (MMP)-2 and MMP-9 secreted by leukemic cells on tight junction proteins ZO-1, claudin-5 and occluding and the permeability of the blood-brain barrier (BBB) and explore the mechanisms of MMP-2 and MMP-9 in leukemic cell infiltration of the central nervous system (CNS). Methods: The mRNA expressions of MMP-2 and MMP-9 in leukemic cell lines SHI-1, HL-60 and U937 were detected by quantitative RT-PCR. The MMP inhibitor GM6001 was used to inhibit the secretion of MMP-2 and MMP-9. RNA interference (RNAi) was used to knock down the expression of MMP-2 and MMP-9. Zymography was used to analyze the secretion of MMP-2 and MMP-9 in the supernatant of different leukemia cell lines treated or untreated with drugs, as well as the RNAi-treated cells. An in vitro BBB model composed of human brain microvascular endothelial cells (BMVECs) was developed on a Matrigel-based insert. Cell invasion through a barrier of Matrigel-based human basement membrane and the BMVECs-based human BBB barrier was assayed to measure the invasive capacity and the capacity to breakdown the BBB of different leukemia cell lines treated or untreated with drugs, as well as the RNAi-treated cells. The morphologic changes of BMVECs after co-culture with different leukemia cell lines treated or untreated with drugs, as well as the RNAi-treated cells in vitro BBB models were observed by invert microscopy and tight junction proteins in these BMVECs were analyzed with a laser-scanning confocal microscope. Results: ①The mRNA expression in different leukemic cell lines shown a pronounced transcription of MMP-2 and - 9, and the transcriptional level in SHI-1 cells was the highest among all leukemic cell lines tested (P<0.01). The data of activities of MMP-2 and -9 were consistent with the results of mRNA expression and SHI-1 displayed higher capacity of invasion (P<0.01). ②After incubation 24h with different leukemic cells, the BMVECs disrupted to loss cell-cell contacts and grew in single cell. Confocal imaging showed down-regulations of ZO-1, claudin-5 and occluding accompanied by the disruption of BBB in vitro models. SHI-1 cells had stronger alterations to BMVECs, tight junction proteins and the permeability of the BBB than HL-60 and U937 cells. However, GM6001 and the knock-down of MMP-2 and MMP-9 altered the responses of BBB. They reduced the degradation of three tight junction proteins with a decreased permeability of BBB. Conclusion: MMP-2 and MMP-9 secreted by leukemic cells could disrupt the BBB by degrading the tight junction proteins ZO-1, claudin-5 and occluding, which contributed the infiltration of leukemic cell into CNS.

[Electroencephalogram power development of cognitive function at age 7 to 12 years: a comparative study between attention deficit hyperactivity disorder and healthy children].

Objective: To compare brain electrical cognitive tasks and brain development between study about 7 to 12 years old attention deficit hyperactivity disorder (ADHD) and normal children. Method: Prospectic case-control study was used. A total of 110 children with ADHD (63 boys and 47 girls) and 116 normal children (66 boys and 50 girls), were enrolled in this study. The electroencephalogram (EEG) was recorded when attention tasks were conducted, the EEG power was extracted from the original data and comparatively analyzed the absolute power (θ, α, ß spectrum) and relative power (θ/total, α/total, θ/α, θ/ß). Result: (1) Absolute power: ADHD children θ absolute power was higher than that of normal children in Pz lead ((52±28)vs. (40±30)µV2, t=3.906, P<0.05), with statistical significance. (2) Relative power: θ/total, θ/α, θ/ß in ADHD are higher than normal children(0.23±0.07 vs. 0.20±0.05, 1.35±0.76 vs. 1.00±0.56, 4.75±2.49 vs. 3.56±2.08, t=2.900 and 3.954 and 3.901, P=0.004 and 0.000 and 0.000), α/total in ADHD is lower (0.21±0.09 vs. 0.24±0.10, t=-2.517, P=0.013). (3) The comparative study of the development of EEG power θ/ß between ADHD and normal children showed age-related correlation in both groups (r=-0.378 and -0.398, P=0.000 for both). Conclusion: ADHD children's EEG power on slow spectrum was higher than that of the normal children, it was more significant in the parietal region than in frontal region. With the increase of age, the θ relative power in ADHD and normal children gradually declined, in the normal children it linearly related, but in ADHD there was no significant regularity. θ/ß can be used as a sensitive index to assess ADHD children's cognitive function.

[The clinical features of patients with lymphoplasmacytic diseases harboring MyD88 L265P mutation].

Objective: To explore the clinical features of lymphoplasmacytic diseases with MyD88 L265P mutation. Methods: To analyze the distribution of MYD88 L265P mutation in patients with lymphoplasmacytic diseases by using of ARMS PCR-CE. Results: There were 25(30.9%) MyD88 L265P mutated patients in 81 patients. The mutation was frequently observed in 14 patients with WM (77.8%, 14/18), 2 patients with lymphoplasmacytic lymphoma (66.7%, 2/3), 1 acute lymphocytic leukemia patient (50.0%, 1/2), 3 multiple myeloma patients (30.0%, 3/10), 1 patient with monoclonal gammopathy of undetermined significance (25%, 1/4), 3 patients with chronic lymphocytic leukemia (13.0%, 3/23) and 1 lymphoma patient (4.8%, 1/21). 20 (80%, 20/25) patients were identified with IgM subtype. Compared with wild-type group of 56 cases, mutated patients were older (median age: 67 years vs 55 years, P< 0.001), with lower WBC count (median count: 5.23 × 109/L vs 10.80 × 109/L, P=0.001), lower HGB level (median count: 85 g/L vs 119 g/L, P<0.001). Conclusion: MyD88 L265P mutation was mainly observed in patients with IgM subtype lymphoplasmacytic diseases, and Waldenstrom' s macroglobulinemia was the most common disease. Compared with the wild-type group, patients with MyD88 L265P mutation were older and had lower WBC count, lower level of HGB. However, further studies were needed to test the prognostic value of MyD88 L265P mutation.

A homologue of the mammalian multidrug resistance gene (mdr) is functionally expressed in the intestine of Xenopus laevis.

P-glycoprotein is an integral membrane protein that functions in multidrug resistance (MDR) cells as a drug efflux pump to maintain intracellular concentrations of antitumor drugs below cytotoxic levels. A homologue of the mammalian mdr gene has been isolated and characterized from Xenopus laevis (Xe-mdr). The cDNA was isolated from a tadpole cDNA library using the full length mouse mdrlb cDNA as a probe. The Xe-mdr encodes a protein that is 66% identical to the mouse mdrlb and 68% identical to the human mdrl. The predicted structure of the Xe-mdr gene product identifies twelve membrane spanning domains and two ATP binding sites both of which are the hallmark of the ABC (ATP binding cassette) transporters. Xe-mdr mRNA is expressed as a single message of 4.5 kb and is found predominantly in the intestine. Xe-mdr message is increased 3- to 4-fold in the ileum compared to the rest of the small intestine. In situ hybridization of sequential sections from the small intestine localized the expression of the Xe-mdr to the cells lining the lumenal epithelium. Brush border membrane vesicles prepared from the small intestine of Xenopus laevis effluxed vinblastine in an ATP-dependent manner. Efflux was decreased by verapamil, a known inhibitor of P-glycoprotein function. These studies indicate that the structure of Xe-mdr has been conserved and suggest that the protein has a role in maintaining the function of the normal intestine in Xenopus.

Analysis of MDR1 expression in normal and malignant endometrium by reverse transcription-polymerase chain reaction and immunohistochemistry.

The purpose of this study was to quantitate the expression of human MDR1 mRNA levels in normal endometrium and in endometrial carcinoma and to determine the association of MDR1 levels with prognostic indicators. Endometrial samples from 43 postmenopausal patients with endometrial carcinoma and 38 patients (controls) with benign disease undergoing hysterectomy were snap-frozen. MDR1 levels were determined by quantitative reverse transcription-PCR (RT-PCR) and compared to sensitive and resistant cell lines. Immunohistochemistry was done with MM4.17, an anti-MDR1 antibody, on paraffin sections, and the results were compared to those obtained from RT-PCR. Data was analyzed using the Kruskal-Wallis and Bonferroni tests, setting the P value at 0.05. In both postmenopausal endometrial tissue and tumors, MDR1 expression was localized to the epithelial cell layer. Comparison of immunohistochemistry and RT-PCR results demonstrated a correlation of 80%. In control patients, MDR1 expression was significantly higher in postmenopausal endometrium (n = 15) than in the proliferative premenopausal endometrium (n = 15; P = 0.0024). MDR1 expression in all tumors was lower than that measured in the postmenopausal controls. Between each tumor group, there was no significant difference in the MDR1 levels observed. MDR1 expression was significantly lower in patients with high nuclear grade (n = 18) tumors when compared to patients with low nuclear grade (n = 14; P = 0.04) tumors. Comparison of MDR1 levels with multiple prognostic indicators for endometrial cancer was only significant for nuclear grade. The data indicate that MDR1 expression is not a major component of the drug resistance observed in primary endometrial tumors.

Taxol: mechanisms of action and resistance.

Information on the mechanisms of action and of resistance to Taxol, as well as new data from our laboratory on the promoter regions of the genes that encode P-glycoprotein in a murine Taxol-resistant cell line, is discussed. Taxol induces the formation of stable bundles of microtubules, thereby interfering with the normal function of cellular microtubules. The drug can induce the multidrug-resistance (MDR) phenotype that includes the overproduction of P-glycoprotein, a membrane glycoprotein that acts as a drug efflux pump. In human tumors resistant to Taxol, P-glycoprotein could be responsible for maintaining the drug below cytotoxic levels. Analyses of the MDR promoters that are involved in P-glycoprotein expression and overproduction revealed an interesting recombination event in a Taxol-resistant cell line. As an important new clinical agent for the treatment of malignancies, Taxol requires further mechanistic investigations at the preclinical level.

Structure-activity profiles of eleutherobin analogs and their cross-resistance in Taxol-resistant cell lines.

PURPOSE: Eleutherobin, a natural product, is an antimitotic agent that promotes the polymerization of stable microtubules. Although its mechanism of action is similar to that of Taxol, its structure is distinct. A structure-activity profile of synthetic eleutherobin derivatives that have modifications at C3, C8 and C15 was undertaken to define the structural requirements for microtubule stabilization and cross-resistance in Taxol-resistant cell lines. METHODS: The biological activity of five eleutherobin analogs was assessed using three techniques: (1) cytotoxicity and drug-resistance in three paired Taxol-sensitive and -resistant cell lines; (2) polymerization of microtubule protein in vitro in the absence of GTP and (3) induction of microtubule bundle formation in NIH3T3 cells. RESULTS: Eleutherobin had an IC50 value comparable to that of Taxol, whereas neoeleutherobin, which has a carbohydrate domain that is enantiomeric with that of the parent compound, was less cytotoxic and had 69% of the maximum microtubule polymerization ability of eleutherobin. Both of these compounds exhibited cross-resistance in MDRI-expressing cell lines. Removal or replacement of the C15 sugar moiety resulted in reduced microtubule polymerization and cytotoxicity compared to eleutherobin and loss of cross-resistance in the cell lines SKVLB and J7-T3-1.6, both of which express high levels of P-glycoprotein. By contrast, removal of the urocanic acid group at C8 resulted in virtually complete abrogation of biological activity. The compound lost its ability to polymerize microtubules, and its cytotoxicity was reduced by a minimum of 2000-fold in lung carcinoma A549 cells. CONCLUSIONS: Removal or modification of the sugar moiety alters the cytotoxic potency of eleutherobin and its pattern of cross-resistance in Taxol-resistant cells, although such compounds retain a small percentage of the microtubule-stabilizing activity of eleutherobin. The N(1)-methylurocanic acid moiety of eleutherobin, or perhaps some other substituent at the C8 position, is essential for Taxol-like activity. These findings will be important for the future design and the synthesis of new and more potent eleutherobin derivatives.