Intra- and Peri-tumoral Radiomics Based on Dynamic Contrast Enhanced-MRI to Identify Lymph Node Metastasis and Prognosis in Intrahepatic Cholangiocarcinoma.

BACKGROUND: Lymph node metastasis (LNM) in patients with intrahepatic cholangiocarcinoma (iCCA) affects treatment strategies and prognosis. However, preoperative imaging is not reliable enough for identifying LNM. PURPOSE: To develop and validate a radiomics nomogram based on dynamic contrast enhanced (DCE)-MR images for identifying LNM and prognosis in iCCA. STUDY TYPE: Retrospective. SUBJECTS: Two hundred four patients with pathologically proven iCCA who underwent curative-intent resection and lymphadenectomy (training cohort: N = 107, internal test cohort: N = 46, and external test cohort: N = 51). FIELD STRENGTH/SEQUENCE: T1- and T2-weighted imaging, diffusion-weighted imaging and DCE imaging at 1.5 T or 3.0 T. ASSESSMENT: Radiomics features were extracted from intra- and peri-tumoral regions on preoperative DCE-MR images. Imaging features were evaluated by three radiologists, and significant variables in univariable and multivariable regression analysis were included in clinical model. The best-performing radiomics signature and clinical characteristics (intrahepatic duct dilatation, MRI-reported LNM) were combined to build a nomogram. Patients were divided into high-risk and low-risk groups based on their nomogram scores (cutoff = 0.341). Patients were followed up for 1-102 months (median 12) after surgery, the overall survival (OS) and recurrence-free survival (RFS) were calculated. STATISTICAL TESTS: Receiver operating characteristic (ROC) curve, calibration, decision curve, Delong test, Kaplan-Meier curves, log rank test. Two tailed P < 0.05 was considered statistically significant. RESULTS: The nomogram incorporating intra- and peri-tumoral radiomics features, intrahepatic duct dilatation and MRI-reported LNM obtained the best discrimination for LNM, with areas under the ROC curves of 0.946, 0.913, and 0.859 in the training, internal, and external test cohorts. In the entire cohort, high-risk patients had significantly lower RFS and OS than low-risk patients. High-risk of LNM was an independent factor of unfavorable OS and RFS. DATA CONCLUSION: The nomogram integrating intra- and peri-tumoral radiomics signatures has potential to identify LNM and prognosis in iCCA. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

DOA Tracking Based on Unscented Transform Multi-Bernoulli Filter in Impulse Noise Environment.

Aiming at the problem of multiple-source direction of arrival (DOA) tracking in impulse noise, this paper models the impulse noise by using the symmetric α stable (SαS) distribution, and proposes a DOA tracking algorithm based on the Unscented Transform Multi-target Multi-Bernoulli (UT-MeMBer) filter framework. In order to overcome the problem of particle decay in particle filtering, UT is adopted to select a group of sigma points with different weights to make them close to the posterior probability density of the state. Since the α stable distribution does not have finite covariance, the Fractional Lower Order Moment (FLOM) matrix of the received array data is employed to replace the covariance matrix to formulate a MUSIC spatial spectra in the MeMBer filter. Further exponential weighting is used to enhance the weight of particles at high likelihood area and obtain a better resampling. Compared with the PASTD algorithm and the MeMBer DOA filter algorithm, the simulation results show that the proposed algorithm can more effectively solve the issue that the DOA and number of target are time-varying. In addition, we present the Sequential Monte Carlo (SMC) implementation of the UT-MeMBer algorithm.

Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1.

BACKGROUND/AIMS: Acute myeloid leukemia (AML) of French-American-British (FAB) subtypes M0 and M1 are both poorly differentiated AML, but their mutational spectrum and molecular characteristics remain unknown. This study aimed to explore the mutational spectrum and prognostic factors of AML-M0 and M1. METHODS: Sixty-five AML patients derived from The Cancer Genome Atlas (TCGA) database were enrolled in this study. Whole-genome sequencing was performed to depict the mutational spectrum of each patient. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), FAB subtypes and the frequencies of known recurrent genetic mutations were described. Survival was estimated using the Kaplan-Meier methods and log-rank test. Univariate and multivariate Cox proportional hazard models were constructed for event-free survival (EFS) and overall survival (OS), using a limited backward elimination procedure. RESULTS: Forty-six patients had more than five recurrent genetic mutations. FLT3 had the highest mutation frequency (n=20, 31%), followed by NPM1 (n=18, 28%), DNMT3A (n=16, 25%), IDH1 (n=14, 22%), IDH2 (n=12, 18%), RUNX1 (n=11, 17%) and TET2 (n=7, 11%). Univariate analysis showed that age ≥60 years and TP53 mutations had adverse effect on EFS (P=0.015, P=0.036, respectively) and OS (P=0.003, P=0.004, respectively), WBC count ≥50×109/L and FLT3-ITD negatively affected EFS (P=0.003, P=0.034, respectively), whereas NPM1 mutations had favorable effect on OS (P=0.035) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on EFS and OS (all P< 0.001). Multivariate analysis suggested that allo-HSCT and NPM1 mutations were independent favorable prognostic factors for EFS and OS (all P< 0.05), WBC count ≥50×109/L was an independent risk factor for EFS (P=0.002) and TP53 mutations for OS (P=0.043). CONCLUSIONS: Our study provided new insights into the mutational spectrum and molecular signatures of AML-M0 and M1. We proposed that FLT3-ITD, NPM1 and TP53 be identified as markers for risk stratification of AML-M0 and M1. Patients with AML-M0 and M1 would likely benefit from allo-HSCT.

The dual induction of apoptosis and autophagy by SZC014, a synthetic oleanolic acid derivative, in gastric cancer cells via NF-κB pathway.

Oleanolic acid (OA) possesses various pharmacological activities, such as antitumor and anti-inflammation; however, its clinical applications are limited by its relatively weak activities and low bioavailability. In this study, we evaluated the cytotoxic activity of seven novel OA derivatives, one of which, SZC014 [2-(pyrrolidine-1-yl) methyl-3-oxo-olean-12-en-28-oic acid], exhibited the strongest antitumor activity; its anticancer effect on gastric cancer cells and action mechanisms were investigated. The viability of OA and seven synthesized derivatives treating gastric cancer cells was detected using tetrazolium (MTT). Among them, SZC014 exhibited the strongest cytotoxic activity against gastric cancer cells (SGC7901, MGC803, and MKN-45). The effect of SZC014 on cell cycle was identified by propidium iodide (PI) staining assay. The cellular apoptosis induced by SZC014 was tested by annexin V/PI. The cellular morphological changes and ultrastructural structures affected by SZC014 were observed and imaged through inverted phase contrast microscope and transmission electron microscopy. Western blotting was performed to explore the expression of proteins associated with apoptosis (caspase 3, caspase 9, Bax, Bcl-2, and Bcl-xL), autophagy (Beclin 1 and ATG 5), and nuclear factor-κB (NF-κB) signal pathway, respectively. The cytotoxic activities of all the seven synthesized OA derivatives were stronger than that of OA against gastric cancer cells. SZC014 exhibited stronger cytotoxic activity than other OA derivatives, inhibited the proliferation of gastric cancer cells, besides, induced G2/M phase cell cycle arrest in SGC7901 cells. Both apoptosis and autophagy were found simultaneously in SZC014-treated SGC7901 cells. Caspase-dependent apoptosis induced by SZC014 was confirmed to be associated with upregulation of Bax and downregulation of Bcl-2 and Bcl-xL, while upregulation of Beclin 1 and ATG 5 was inferred to be involved in SZC014-induced autophagy. Moreover, treating cells with SZC014 resulted in a decrease in phosphorylation of IκBα and NF-κB/p65 and NF-κB/p65 nuclear translocation. The cytotoxic activities of seven OA derivatives were generally stronger than that of OA, among which, SZC014 possessed the most potent anticancer activity in SGC7901 cells and would be a promising chemotherapic agent for the treatment of gastric cancer.

[Ceramide participates in cell programmed death induced by Type II anti-CD20 mAb].

OBJECTIVE: To explore the exact mechanisms of programmed cell death (PCD) induced by Type II anti-CD20 mAb in CD20+ non-Hodgkin lymphoma (NHL) cells, and to provide theoretical basis for anti-tumor ability of new CD20 mAb.
 METHODS: After incubation with Rituximab (a Type I anti-CD20 mAb) and Tositumomab (a Type II anti-CD20 mAb), Raji cells were stained by annexin V & propidium iodide (PI). The ratio of programmed death cells were measured by two channel flow cytometry (FCM). Before the treatment of anti-CD20 mAbs, Raji cells was incubated with a caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (Z-VAD-FMK) and a dihydroceramide synthase inhibitor fumonisin B1 (FB1) for 30 minutes to assess their inhibitory effect on PCD. High performance liquid chromatography (HPLC) was utilized to compare the ratio of programmed death cells between the pretreatment group (treated by Rituximab and Tositumomab) and the non-pretreatment group. The anti-CD20 mAbs-treated Raji cells were collected, and the ceramide levels in the Raji cells in the different pretreatment groups were also examined by HPLC, and the inhibitory effect of FB1 on the changes of ceramide levels in the Raji cells was measured. The Raji cells were incubated with different concentration C2-ceramide, C2-Ceramide-induced PCD was also evaluated by annexin V & PI staining after 16 hours. 
 RESULTS: Tositumomab (10 µg/mL) but not Rituximab (10 µg/mL) can induce significant PCD (28.6±4.2)% in Raji cells, with significant difference (t=26.48, P<0.01), which cannot be blocked by Z-VAD-FMK with a concentration range from 10 to 30 µmol/L (F=3.01, P>0.05). The cellular ceramide levels in Raji cells were significantly elevated after the treatment of Tositumomab (t=28.48, P<0.01). C2-ceramide can significantly induce PCD in Raji cells in a dose-dependent manner with a concentration range from 5 to 40 µmol/L (F=2.71, P>0.05). The dihydroceramide synthase inhibitor FB1 can significantly inhibit the elevated cellular ceramide levels (F=20.18, P<0.01) and cell programmed death induced by Tositumomab (F=17.02, P<0.01).
 CONCLUSION: Type II but not Type I anti-CD20 mAbs can induce caspase independent PCD in CD20+ NHL cells through the elevation of cellular ceramide levels. The PCD is not associated with classic caspase pathway.

Effectiveness and safety of Xuebijing injection for patients with coronavirus disease 2019: a systematic review and Metaanalysis.

OBJECTIVE: To evaluate the effectiveness and safety of Xuebijing injection (XBJ) on coronavirus disease 2019 (COVID-19) in patients. METHODS: Related studies on multiple biological databases and websites were searched up to December 11, 2021 without language and publication time restrictions. Review Manager V.5.3 and Stata 14 software were used for data analysis. RESULTS: Seven studies were finally included. The Metaanalysis showed that compared with the routine treatment alone, XBJ combined with the routine treatment can reduce the 28day mortality ( = 0.3, 95% : 0.12, 0.74), Creactive protein ( = -12.8, 95% : -23.13, 3.46), erythrocyte sedimentation rate ( = -9.32, 95% : -14.66, -3.98) and interleukin-6 (S = -0.6, 95% : -1.04, -0.17) levels and increase the leukocyte ( = 0.73, 95% : 0.42, 1.04) and lymphocyte count ( = 0.18, 95% : 0.07, 0.29) in peripheral blood; additionally, it has no obvious side effects ( = 1.11, 95% : 0.65, 1.9). There was no evidence that the XBJ combined therapy can improve the nucleic acid conversion rate and computed tomography improvement rate of COVID19 patients. CONCLUSIONS: Preliminary evidence suggests that XBJ combined with routine treatment seems to be more effective than routine treatment for patients with COVID19. Limited by the number and quality of included papers, this finding still needs further validation by more studies.

[The efficacy and safety of valproic acid in combination with low dose chemotherapy on intermediate and high-risk myelodysplastic syndrome].

OBJECTIVE: To evaluate the efficacy and adverse effect of valproic acid (VPA) in combination with low dose chemotherapy on intermediate and high-risk myelodysplastic syndrome. METHODS: A total of 41 patients with intermediate (34) and high-risk (7) myelodysplastic syndrome were retrospectively analyzed. Among them, 19 patients received low dose chemotherapy regimen and 22 received low dose chemotherapy plus VPA. Low dose chemotherapy regimen included: homoharringtonine, 1 - 2 mg×m(-2)×d(-1) intravenously, 14 - 28 d; aclarubicin, 5 - 7 mg×m(-2)×d(-1) intravenously, 1 - 8 d, 15 - 23 d; cytarabine 15 mg/m(2) subcutaneously once every 12 h, 14 - 21 d; and subcutaneously use of granulocyte colony-stimulating factor 200 µg·m(-2)×d(-1) when neutrophil deficiency. The outcome and adverse effect were recorded after the treatment. RESULTS: The overall response rate in the low dose chemotherapy regimen group was 47.4% (9/19), 6 patients (31.6%) achieved complete response (CR). The overall response rate in the VPA group was 77.2% (17/22), 9 patients (40.9%) achieved CR. The overall response rate of the low dose chemotherapy in combination with VPA group was significantly higher than that in the low dose chemotherapy group (P < 0.05) while no difference was found in CR rate. The adverse effect of the low dose chemotherapy in combination with VPA regimen was tolerated. CONCLUSION: With acceptable adverse effect, the low dose chemotherapy in combination with VPA regimen is effective for the treatment of intermediate and high-risk myelodysplastic syndrome. Long-term outcome needs further investigation.

Down-regulation of miR-203a by lncRNA PVT1 in multiple myeloma promotes cell proliferation.

INTRODUCTION: Emerging evidence has indicated that long non-coding RNAs (lncRNAs) play vital roles in multiple myeloma (MM) development and progression. However, the underlying mechanism of PVT1 in MM remains unclear. MATERIAL AND METHODS: QRT-PCR was used to detect the expression of PVT1 and miR-203a in MM samples and cell lines. The effects of PVT1 on MM cell proliferation and apoptosis were determined by CCK8 assay and flow cytometer assay, respectively. Bioinformatics methods were used to identify the downstream target miRNAs of PVT1. RESULTS: We found that the expression of PVT1 was upregulated in MM samples and cell lines (p < 0.05), while the expression of miR-203a was downregulated in MM samples and cell lines (p < 0.05). There was a negative correlation between PVT1 expression and miR-203a expression in MM samples (p < 0.05). In in vitro function assays, we found that PVT1 inhibition suppressed MM cell proliferation and induced MM cell apoptosis (p < 0.05). The bioinformatics approach predicted that PVT1 sponge miR-203a would modulate MM cells. Rescue experiments confirmed the recovering roles of miR-203a for PVT1 on MM progression. CONCLUSIONS: In the present study, we found that lncRNA PVT1 could promote MM cell proliferation and induce cell apoptosis by inhibiting miR-203a expression. Therefore, PVT1 may represent a potential therapeutic target for the treatment of MM patients.

Antitumor effect of triptolide in T-cell lymphoblastic lymphoma by inhibiting cell viability, invasion, and epithelial-mesenchymal transition via regulating the PI3K/AKT/mTOR pathway.

INTRODUCTION: T-cell lymphoblastic lymphoma (T-LBL) is a widely disseminated disease worldwide. Triptolide (TPL) is purified from Chinese herb and displays anti-inflammatory, anti-fertility, anti-tumor and immunosuppressive effects. MATERIALS AND METHODS: Here, in vitro and in vivo experiments were conducted to investigate the anti-tumor effect of TPL treatment in T-LBL and the potential mechanism in T-LBL progression. RESULTS: TPL inhibited cell proliferation of T-LBL cells (Jurkat cells and Molt-3 cells) in a dose-dependent manner. Flow cytometry analysis showed that cell apoptosis rate was increased by TPL treatment. TPL also up-regulated the expression of Caspase-3, Bax and down-regulated the expression of Bcl-2, indicating that TPL promoted apoptosis in Jurkat cells. Moreover, TPL inhibited invasion ability of Jurkat cells and down-regulated the expression of MMP-3 and MMP-9 in a dose-dependent manner. The expression of Snail, Slug, Twist and Integrin αVß6 was decreased and the expression of E-cadherin was increased by TPL treatment, indicating that TPL inhibited EMT of Jurkat cells. Apart from that, TPL treatment attenuated the phoslevels of PI3K, Akt and mTOR and suppressed AKT activation compared with control group, suggesting that TPL inhibited PI3K/Akt/mTOR signal pathway in T-LBL. In vivo experiments showed that TPL inhibited tumor growth of T-LBL and promoted apoptosis of tumor cells. The expression of PCNA, Bcl-2, Snail, p-PI3K, p-Akt and mTOR was suppressed by TPL in a dose-dependent manner, suggesting that TPL suppressed tumor growth and promoted apoptosis of tumor cells by inhibiting PI3K/Akt/mTOR signal pathway in T-LBL. CONCLUSION: In conclusion, TPL exerted anti-tumor effect in T-LBL by inhibiting cell viability, invasion and EMT via regulating the PI3K/AKT/mTOR pathway.

Mutational spectrum and prognostic stratification of intermediate-risk acute myeloid leukemia.

The mutational spectrum and prognostic stratification of intermediate-risk acute myeloid leukemia (IR-AML), which accounts for a substantial number of AML, are unclear. In order to explore the prognostic significance of the mutational spectrum in IR-AML, 106 IR-AML patients were collected from The Cancer Genome Atlas database. Sixty-two patients underwent chemotherapy-only, forty-four proceeded to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Fifty-five patients had more than five recurrent genetic mutations. NPM1 had the highest mutation frequency, followed by DNMT3A, FLT3, RUNX1, IDH2, IDH1, and TET2. In all patients, allo-HSCT was an independent favorable factor for EFS and OS (P = 0.036, P = 0.001, respectively); age ≥60 years, FLT3-ITD and mutations in DNMT3A and RUNX1 were independent risk factors for survival (all P < 0.05). In the chemotherapy-only group, multivariate analysis showed that age ≥60 years was an independent risk factor for EFS and OS (P = 0.008, P = 0.017, respectively). In the allo-HSCT group, multivariate analysis indicated that MLL-PTD was an independent risk fact for EFS (P = 0.037), FLT3-ITD and RUNX1 mutations independently contributed to poor OS (P = 0.035, P = 0.014, respectively). In conclusion, older age was an important risk factor for IR-AML patients undergoing chemotherapy-only; FLT3-ITD, MLL-PTD and RUNX1 mutations were significant risk factors for IR-AML patients who received allo-HSCT.

Prognostic significance of microRNA-99a in acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation.

Overexpression of microRNA-99a (miR-99a) have been associated with adverse prognosis in acute myeloid leukemia (AML). Nevertheless, whether it also predicts poor outcome in post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) AML patients remains unclear. To further elucidate the prognostic value of miR-99a, 74 AML patients with miR-99a expression report who underwent allo-HSCT from The Cancer Genome Atlas database were identified and grouped into either miR-99ahigh or miR-99alow based on their miR-99a expression levels relative to the median. Two groups had similar clinical and molecular characteristics except that miR-99ahigh group had fewer patients of the French-American-British M4 subtype (P = 0.018) and more frequent CEBPA mutations (P = 0.005). Univariate analysis indicated that high miR-99a expression was unfavorable for both event-free survival (EFS) and overall survival (OS; P = 0.029; P = 0.012, respectively). Multivariate analysis suggested that high miR-99a expression was an independent risk factor for both EFS and OS in AML patients who underwent allo-HSCT [hazard ratio (HR) 1.909, 95% confidence interval (CI) 1.043-3.494, P = 0.036 and HR 2.179, 95% CI 1.192-3.982, P = 0.011, respectively]. Our results further proved that high miR-99a expression could predict worse outcome in AML patients, even in those who underwent intensive post-remission therapy such as allo-HCST.

Nine-year changes in intraocular pressure: the Barbados Eye Studies.

OBJECTIVE: To describe temporal changes in intraocular pressure (IOP) and associated risk factors after 9 years of follow-up in a population of African descent. METHODS: Changes in IOP were evaluated in 2298 participants without glaucoma or IOP-lowering treatment at baseline. Risk factor analyses used a multiple regression approach with mixed effects, which accounted for intereye correlation. RESULTS: The mean 9-year change in IOP was small, with relatively large dispersion (mean +/- SD, 0.4 +/- 4.0 mm Hg). Only 6.5% of persons with IOP of 21 mm Hg or less at baseline had elevated IOP greater than 21 mm Hg after 9 years. Mean IOP increases were largest in persons aged 50 to 59 years at baseline (mean +/- SD, 0.9 +/- 4.3 mm Hg), whereas IOP decreased in persons 70 years or older (mean +/- SD, -0.6 +/- 4.2 mm Hg). In multivariate analyses, IOP changes were positively associated with male sex, hypertension, diabetes history, and higher systolic and diastolic blood pressure at baseline, as well as with increases in blood pressure throughout 9 years (P<.05). CONCLUSIONS: After long-term follow-up, minimal changes in IOP were observed in this African-origin population. The consistent relationships of hypertension and diabetes to IOP, a major glaucoma risk factor, underscore the public health importance of controlling these systemic conditions in black populations, where glaucoma incidence is high.

Rats withdrawn from ethanol rapidly re-acquire membrane tolerance after resumption of ethanol feeding.

The time course for the re-acquisition of membrane tolerance to the disordering effects of ethanol in vitro has been determined for liver microsomes obtained from chronically ethanol-fed rats that were withdrawn from ethanol for 2-4 days (during which tolerance is lost) followed by resumption of ethanol feeding. Naive rats require 28-35 days of chronic ethanol feeding to develop membrane tolerance. Microsomal membranes regain partial sensitivity to ethanol disordering after 2-3 days of withdrawal and regain the complete sensitivity observed in membranes from untreated control rats after 4 days of withdrawal. The period of ethanol re-feeding required for the re-acquisition of membrane tolerance was dependent on the withdrawal period, with tolerance appearing sooner if the withdrawal period was shorter. The time course for the re-development of tolerance in previously tolerant animals was considerably faster (4-14 days) than in naive rats being administered the ethanol diet for the first time (35 days). Microsomes from rats that were withdrawn for 2 days (which retained partial tolerance) and then re-fed the ethanolic-diet required only 4 days to re-acquire membrane tolerance. Microsomes from rats withdrawn 3 days required 8 days and those withdrawn 4 days required 15 days for full tolerance to re-develop. The same time-course for the re-acquisition of membrane tolerance was observed in either intact microsomes or in liposomes prepared from extracted microsomal total phospholipids. Phosphatidylinositol (PI) has previously been reported to be responsible for conferring membrane tolerance to liver microsomes in ethanol-fed rats (Taraschi, T.F., Ellingson, J.S., Wu, A., Zimmerman, R. and Rubin, E. (1986) Proc. Natl. Acad. Sci. USA 83, 9398-9402). The time course for re-acquisition of membrane tolerance by liver microsomes following ethanol withdrawal and resumption of ethanol feeding correlated with the ability of PI to confer tolerance.

Sodium selenite inhibits leukemia HL-60 cell proliferation and induces cell apoptosis by enhancing the phosphorylation of JNK1 and increasing the expression of p21 and p27.

Selenium is an essential trace element and has shown chemopreventive or therapeutic activities on human solid cancers; however, whether it has anticancer effects on leukemia has not yet been elucidated. The present study was designed to determine the role of selenium on HL-60 human promyelocytic leukemia cells. We found that 100 nM of sodium selenite (Se) had no significant effects on cell proliferation, apoptosis and the cell cycle; however, a higher concentration of 250 nM of Se significantly inhibited cell proliferation, promoted apoptosis and induced cell cycle arrest at the S phase after 48 h of treatment (P<0.05), thus demonstrating the anticancer activities of selenium in leukemia. However, the decrease in c-Jun NH2-terminal kinase 1 (JNK1) expression by targeting JNK1 using small interfering RNA attenuated the inhibitory effects of Se on cell proliferation and the induction of apoptosis. Mechanistic studies showed that the anticancer activities of Se were associated with the enhanced phosphorylation of JNK1 and the increased expression of the cell cycle regulators, p21 and p27, as well as the downregulation of cyclin D1. Our data provide further evidence that the appropriate concentration of selenium has therapeutic potential in leukemia.

The immunoglobulin light chain locus of the turkey, Meleagris gallopavo.

To date, most jawed vertebrate species encode more than one immunoglobulin light (IgL) chain isotypes. It has been shown that several bird species (chickens, white Pekin or domestic duck, and zebra finches) exclusively express lambda isotype. We analyze here the genomic organization of another bird species turkey IgL genes based on the recently released genome data. The turkey IgL locus located on chromosome 17 spans approximately 75.2kb and contains a single functional V(λ) gene, twenty V(λ) pseudogenes, and a single functional J(λ)-C(λ) block. These data suggest that the genomic organization of bird IgL chain genes seems to be conserved. Ten cDNA clones from turkey Igλ chain containing almost full-length V(λ), J(λ) and C(λ) segments were acquired. The comparison of V(λ) cDNA sequences to all the germline V(λ) segments suggests that turkey species may be generating IgL chain diversity by gene conversion and somatic hypermutation like the chicken. This study provides insights into the immunoglobulin light chain genes in another bird species.

[Effect of recombinant human interleukin 11 on recovery of platelets after peripheral blood hematopoietic stem cell transplantation].

The aim of this study was to explore the effect of recombinant human interleukin 11 (rhIL-11) on platelet recovery after peripheral blood hematopoietic stem cell transplantation and its side-effects. 20 patients with hematologic malignancies treated by allogeneic peripheral blood stem cell transplantation (PBSCT) were randomly divided into test and control groups. The patients in test group were treated with rhIL-11 since the day 6 after PBSCT, while the patients in control group were given supporting treatment. The results showed that the average time of the platelet to recover to 20 x 10(9)/L was 22.8 days in test group and 27.3 days in control group (p < 0.01). The average time for platelet to recover to 50 x 10(9)/L was 25.7 days in test group, and 32.3 days in control group (p < 0.01). The average number of megakaryocytes was 15.6 in test group, and 7.8 in control group on day 30 after PBSCT (p < 0.01). In conclusion, the rhIL-11 is able to accelerate platelet recovery after peripheral blood hematopoietic stem cell transplantation.

Clinical manifestations, laboratory findings and complications of pediatric scrub typhus in eastern Taiwan.

BACKGROUND: Scrub typhus is a clinically important endemic disease in Taiwan. The aims of this study were to analyze the clinical manifestations, laboratory data and complications of pediatric scrub typhus in eastern Taiwan. PATIENTS AND METHODS: We searched medical records for all patients with scrub typhus who were hospitalized between 1992 and 2002 at the Taitung branch of Mackay Memorial Hospital, Taiwan. Records of children under the age of 18 with a confirmed diagnosis were selected for retrospective review. RESULTS: During the study period, 145 patients fulfilled the diagnostic criteria for scrub typhus, of whom 106 (73%) were adults and 39 (27%) were children. The mean age of the children was 7.6+/-4.6 years. The most common clinical manifestations of pediatric scrub typhus were fever (n=39; 100%), cough (n=28; 72%), anorexia (72%), eschar (69%), chill (67%) and lymphadenopathy (64%). The most common complications were hepatic dysfunction (77%) and pneumonitis (54%). Three children (8%) required intensive care, but the overall survival rate was 97%. One child died with multi-organ failure within 8 hours after admission. CONCLUSION: Scrub typhus should be considered in children with fever and hepatic dysfunction, particularly in those with a history of environmental exposure in an endemic area for scrub typhus. The presence of an eschar offers an important diagnostic clue, but not for all cases. Children with scrub typhus may develop serious complications and may even die if appropriate treatment is not given. Doxycycline is an effective antibiotic for pediatric scrub typhus in Taiwan.

Cardiovascular and respiratory considerations with pharmacotherapy of glaucoma and ocular hypertension.

Glaucoma and ocular hypertension are highly prevalent conditions in individuals over the age of 40 and are commonly seen together in patients with cardiovascular disease. Many of the antiglaucoma medications, when systemically absorbed, affect the sympathetic and parasympathetic nervous systems of patients and can cause cardiovascular toxicity. Such adverse effects are frequently associated with the long-term use of potentially toxic agents in elderly people, who are most prone to chronic eye disease. Moreover, patients may not associate their symptoms with the topical eye medications, and consequently may not report adverse drug effects. Drug-drug interactions can also occur when patients are taking medications for both cardiovascular disease and glaucoma. In this review, the systemic toxicity of these agents is reviewed, along with possible drug-drug interactions. Mention is made of other antiglaucoma medications used alone and in combination with topical beta-blockers. Identification of genetic loci-a bold new step toward glaucoma treatment-is mentioned briefly at the end of the article.