[Doublecortin-like kinase 1 activates Hippo pathway to promote migration, invasion and proliferation of pancreatic cancer cells].

Objective: To explore the mechanism of Doublecortin-like kinase 1 (DCLK1) in promoting cell migration, invasion and proliferation in pancreatic cancer. Methods: The correlation between DCLK1 and Hippo pathway was analyzed using TCGA and GTEx databases and confirmed by fluorescence staining of pancreatic cancer tissue microarrays. At the cellular level, immunofluorescence staining of cell crawls and western blot assays were performed to clarify whether DCLK1 regulates yes associated protein1 (YAP1), a downstream effector of the Hippo pathway. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to analyze the expressions of YAP1 binding transcription factor TEA-DNA binding proteins (TEAD) and downstream malignant behavior-promoting molecules CYR61, EDN1, AREG, and CTGF. Transwell test of the DCLK1-overexpressing cells treated with the Hippo pathway inhibitor Verteporfin was used to examine whether the malignant behavior-promoting ability was blocked. Analysis of changes in the proliferation index of experimental cells used real-time label-free cells. Results: TCGA combined with GTEx data analysis showed that the expressions of DCLK1 and YAP1 molecules in pancreatic cancer tissues were significantly higher than those in adjacent tissues (P<0.05). Moreover, DCLK1was positively correlated with the expressions of many effectors in the Hippo pathway, including LATS1 (r=0.53, P<0.001), LATS2 (r=0.34, P<0.001), MOB1B (r=0.40, P<0.001). In addition, the tissue microarray of pancreatic cancer patients was stained with multicolor fluorescence, indicated that the high expression of DCLK1 in pancreatic cancer patients was accompanied by the up-regulated expression of YAP1. The expression of DCLK1 in pancreatic cancer cell lines was analyzed by the CCLE database. The results showed that the expression of DCLK1 in AsPC-1 and PANC-1 cells was low. Thus, we overexpressed DCLK1 in AsPC-1 and PANC-1 cell lines and found that DCLK1 overexpression in pancreatic cancer cell lines promoted YAP1 expression and accessible to the nucleus. In addition, DCLK1 up-regulated the expression of YAP1 binding transcription factor TEAD and increased the mRNA expression levels of downstream malignant behavior-promoting molecules. Finally, Verteporfin, an inhibitor of the Hippo pathway, could antagonize the cell's malignant behavior-promoting ability mediated by high expression of DCLK1. We found that the number of migrated cells with DCLK1 overexpressing AsPC-1 group was 68.33±7.09, which was significantly higher than 22.00±4.58 of DCLK1 overexpressing cells treated with Verteporfin (P<0.05). Similarly, the migration number of PANC-1 cells overexpressing DCLK1 was 65.66±8.73, which was significantly higher than 37.00±6.00 of the control group and 32.33±9.61 of Hippo pathway inhibitor-treated group (P<0.05). Meanwhile, the number of invasive cells in the DCLK1-overexpressed group was significantly higher than that in the DCLK1 wild-type group cells, while the Verteporfin-treated DCLK1-overexpressed cells showed a significant decrease. In addition, we monitored the cell proliferation index using the real-time cellular analysis (RTCA) assay, and the proliferation index of DCLK1-overexpressed AsPC-1 cells was 0.66±0.04, which was significantly higher than 0.38±0.01 of DCLK1 wild-type AsPC-1 cells (P<0.05) as well as 0.05±0.03 of DCLK1-overexpressed AsPC1 cells treated with Verteporfin (P<0.05). PANC-1 cells showed the same pattern, with a proliferation index of 0.77±0.04 for DCLK1-overexpressed PANC-1 cells, significantly higher than DCLK1-overexpressed PANC1 cells after Verteporfin treatment (0.14±0.05, P<0.05). Conclusion: The expression of DCLK1 is remarkably associated with the Hippo pathway, it promotes the migration, invasion, and proliferation of pancreatic cancer cells by activating the Hippo pathway.

[Clinical characteristics and prognosis of 46 patients with macrofocal multiple myeloma].

The clinical characteristics, laboratory results, response to treatment, and prognosis of 46 macrofocal multiple myeloma(MFMM) patients at our center from January 2013 to December 2019 were analyzed retrospectively. The other 92 patients were selected as matched-controls based on diagnostic period and treatment. Among the 1 137 MM patients, 46 patients met the definition criteria of MFMM (4.0%), with median age 56 years, which was not statistically different from whole MM population (P=0.066). According to the international staging system (ISS) and Revised ISS, the proportion of patients with advanced stage in MFMM group was less common than that of controls (P<0.05). More plasmacytomas in MFMM patients were presented (43.5% vs. 18.5%, P<0.05). Regarding cytogenetic abnormalities, there were minor patients manifesting high-risk features in MFMM group (15.8% vs. 32.2%, P=0.058). Translocation(11;14) could be detected in 32.4% MFMM patients and 9.4% typical myeloma patients (P<0.05). The treatment regimens were comparable. As to the best response of treatment, the complete response (CR) rate in MFMM group was significantly higher than that of controls (78.3% vs. 60.9%, P<0.05). The median follow-up time was 37.9 months. The median progression-free survival in MFMM and control groups were 77.5 vs. 39.8 months, respectively (P<0.05). The overall survival (OS) of MFMM patients was significantly longer (not reached vs. 68.2 months, P<0.05).

[Efficacy and prognosis of newly diagnosed multiple myeloma patients treated with bortezomib, lenalidomide and dexamethasone].

Objective: To evaluate the efficacy of VRD (bortezomib+lenalidomide+dexamethasone) in newly diagnosed multiple myeloma (NDMM) patients as well as the effect of the regimen on the long-term prognosis. Methods: The clinical characteristics, survival rates, response rates and minimal residual disease (MRD) of patients with NDMM at Institute of Hematology & Blood Diseases Hospital from January 1, 2013 to January 1, 2020 were retrospectively analyzed. Subgroup analysis was also performed among groups according to the cytogenetics and autologous stem cell transplantation (ASCT) of patients. Results: A total of 87 patients were retrospectively analyzed. The age[M(Q1,Q3)] of all patients was 56 (51, 61) years and males and females accounted for 58.6% (51/87) and 41.4% (36/87), respectively. The overall response rate (ORR) was 95.9% (71/74) after 2 courses of induction therapy, with 13.5% (10/74) achieving the deep response [complete response (CR) or better] and 51.3% (38/74) of patients achieving a very good partial response (VGPR) or better. After 4 courses of induction therapy, the ORR achieved 95.2% (60/63), and the proportions of the deep response and VGPR or better grew up to 46.0% (29/63) and 77.7% (49/63). According to the treatment, the patients (≤65 years old) were divided into transplantation group and non-transplantation group. After the induction therapy, 88.8% (32/36) of patients in the transplantation group achieved VGPR or better, and 55.5% (20/36) reached the deep response. After the transplantation, the proportion increased to 97.1% (34/35) and 77.2% (27/35), respectively(88.8% vs 97.1%,P=0.174;55.5% vs 77.2%,P=0.055), with the rate of undetectable MRD increasing from 44.4% (16/36) to 77.8% (28/36) (P=0.004). In the non-transplantation group, 74.2% (23/31) of patients achieved VGPR or better after 4 courses of induction therapy, 35.5% (11/31) of the patients achieved deep response and the rate of undetectable MRD was 37.0% (10/27). Compared with the non-transplantation group, transplantation was associated with a higher rate of complete response (89.5% vs 53.1%, P<0.001) and a lower rate of MRD detection(78.4% vs 55.2%, P=0.045). The median follow-up time of all patients was 26.3 months (20.8, 33.8). The median progression-free survival and overall survival were not reached. The three-year PFS and OS rates were 78.4% and 87.2%, respectively. None of the standard-risk group, the high-risk group, the transplantation group and non-transplantation group achieved the median PFS and OS. Conclusions: VRD regimen has a promising efficacy and results in a substantial survival benefit. ASCT after VRD induction therapy is associated with higher rate of deep response, higher rate of undetectable MRD and longer survival.

Retraction notice to "30MO ORIENT-3: A randomized, open-label, phase III study of sintilimab versus docetaxel in previously treated advanced/metastatic squamous non-small cell lung cancer (sqNSCLC)": [Annals of Oncology Volume 31, Supplement 7, December 2020, Page S1428].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article was retracted at the request of the authors. The authors of this abstract have advised that full agreement between authors and sponsors on publication of the abstract has not been reached and they are therefore unable to publish this data at present.

[The effect of anti-VEGF therapy on the expression levels of TGF-ß and related microRNAs in the vitreous of patients with proliferative diabetic retinopathy].

Objective: To investigate the effect of anti-vascular endothelial growth factor (VEGF) therapy on the expression levels of transforming growth factor-beta (TGF-ß) and its related microRNAs in the vitreous of patients with proliferative diabetic retinopathy (PDR). Methods: This cross-sectional study included 67 patients (67 eyes), 38 males and 29 females, aged (54.37±11.70) years, who underwent vitrectomy from June 2020 to February 2021. There were 45 PDR patients (45 eyes), including 29 patients (29 eyes) without anti-VEGF therapy in the disease group and 16 patients (16 eyes) who were admitted at 7 days after anti-VEGF therapy in the treatment group. The other 22 idiopathic macular hole patients (22 eyes) were in the negative control group. The microRNA (hsa-miR-24-3p and hsa-miR-197-3p) levels in the vitreous of 36 patients (12 cases randomly chosen from each group) were detected by quantitative reverse transcription polymerase chain reaction. The levels of TGF-ß and VEGF-A in the vitreous of 67 patients were detected by enzyme-linked immunosorbent assay. Target gene prediction of hsa-miR-24-3p and hsa-miR-197-3p was performed on RNAhybrid, miRanda and TargetScan7.2 databases, and pathway enrichment analyses were conducted for all target mRNAs. One-way ANOVA was used to compare the levels of growth factors and microRNAs among the three groups, and the least significant difference method was used for multiple comparisons between groups. Pearson correlation test was used to analyze the correlation between growth factors and microRNAs. Results: The expression levels of VEGF-A, TGF-ß, hsa-miR-24-3p and hsa-miR-197-3p were (158.15±17.72) pg/ml, (640.47±24.80) pg/ml, 0.81±0.11 and 1.07±0.15 in the control group, (1 047.54±26.61) pg/ml, (3 553.17±92.61) pg/ml, 8.50±2.33 and 12.23±3.38 in the disease group, and (778.10±27.73) pg/ml, (3 376.02±78.83) pg/ml, 4.54±0.67 and 3.90±0.65 in the treatment group, respectively. All indicators were significantly higher in the disease group than those in the control group (F=355.581, 440.538, 7.546 and 7.546; all P<0.05). The expression levels of VEGF-A, hsa-miR-24-3p and hsa-miR-197-3p in the treatment group were significantly lower than those in the disease group (all P<0.05). The concentration of TGF-ß was not statistically significantly lower in the treatment group compared to the disease group. The concentrations of VEGF-A and TGF-ß were significantly positively correlated with the expression levels of hsa-miR-24-3p and hsa-miR-197-3p in the vitreous of randomly chosen 36 patients (r=0.48, 0.51, 0.40 and 0.42; all P<0.05). Pathway enrichment analysis showed that some target mRNAs of hsa-miR-24-3p and hsa-miR-197-3p were involved in VEGF and TGF-ß signal pathways. Conclusions: In the vitreous of patients with PDR, hsa-miR-24-3p and hsa-miR-197-3p were positively related to VEGF-A and TGF-ß, and may be potential risk factors. Anti-VEGF treatment can significantly reduce the expression level of TGF-ß-related microRNAs, namely hsa-miR-24-3p and hsa-miR-197-3p, but cannot effectively reduce the concentration of TGF-ß, suggesting that combined anti-TGF treatment may be beneficial for delaying the progression of PDR. Furthermore, it may be a new research direction of PDR to validate the target mRNAs of hsa-miR-24-3p and hsa-miR-197-3p involved in VEGF and TGF-ß signal pathways. (Chin J Ophthalmol, 2021, 57: 922-929).

Application Prospects and Prospect of Metabolomics in the Identification of Sudden Cardiac Death.

ABSTRACT: In cases of sudden death, the prevention of sudden cardiac death and the analysis of the cause of death after sudden cardiac death have always been a difficult problem. Therefore, clinical research and forensic pathological identification of sudden cardiac death are of great significance. In recent years, metabolomics has gradually developed into a popular field of life science research. The detection of "metabolic fingerprints" of biological fluids can provide an important basis for early diagnosis of diseases and the discovery of potential biomarkers. This article reviews the current research status of sudden cardiac death and the research on metabolomics of cardiovascular diseases that is closely related to sudden cardiac death and analyzes the application prospects of metabolomics in the identification of the cause of sudden cardiac death.

RETRACTED: ORIENT-3: A randomized, open-label, phase III study of sintilimab versus docetaxel in previously treated advanced/metastatic squamous non-small cell lung cancer (sqNSCLC).

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article was retracted at the request of the authors. The authors of this abstract have advised that full agreement between authors and sponsors on publication of the abstract has not been reached and they are therefore unable to publish this data at present.

Development of predictive nomograms for clinical use to quantify the risk of isolating resistance prone organisms in patients with infected foot ulcers.

Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) have been considered prevalent pathogens in foot infections. However, whether empiric therapy directed against these organisms is necessary, and in whom to consider treatment, is rather unclear. The aim of this study was to develop predictive algorithms for forecasting the probability of isolating these organisms in the infected wounds of patients in a population where the prevalence of resistant pathogens is low. This was a retrospective study of regression model-based risk factor analysis that included 140 patients who presented with infected, culture positive foot ulcers to two urban hospitals. A total of 307 bacteria were identified, most frequently MRSA (11.1%). P. aeruginosa prevalence was 6.5%. In the multivariable analysis, amputation (odds ratio (OR) 5.75, 95% confidence interval (CI) 1.48-27.63), renal disease (OR 5.46, 95% CI 1.43-25.16) and gangrene (OR 2.78, 95% CI 0.82-9.59) were identified as risk factors associated with higher while diabetes (OR 0.07, 95% CI 0.01-0.34) and Infectious Diseases Society of America infection severity >3 (OR 0.18, 95% CI 0.03-0.65) were associated with lower odds of P. aeruginosa isolation (C statistic 0.81). Similar analysis for MRSA showed that amputation was associated with significantly lower (OR 0.29, 95% CI 0.09-0.79) risk, while history of MRSA infection (OR 5.63, 95% CI 1.56-20.63) and osteomyelitis (OR 2.523, 95% CI 1.00-6.79) was associated with higher odds of isolation (C statistic 0.69). We developed two predictive nomograms with reasonable to strong ability to discriminate between patients who were likely of being infected with P. aeruginosa or MRSA and those who were not. These analyses confirm the association of some, but also question the significance of other frequently described risk factors in predicting the isolation of these organisms.

[Comorbidity of Chronic Obstructive Pulmonary Disease and Cardiovascular Diseases: Place of Therapy with Modern ß-Adrenoblockers].

Chronic obstructive pulmonary disease (COPD) is the fourth largest cause of worldwide mortality.  Presence of comorbidities is registered in 96% of COPD patients. The most important of these are cardiovascular diseases (coronary artery disease, arterial hypertension, chronic heart failure), which contribute to COPD patients' mortality in every third case. COPD and cardiovascular diseases have common risk factors and pathogenesis mechanisms. Cardioselective beta-blockers reduce morbidity risk and frequency of COPD exacerbation, are effective and safe in treatment of COPD patients.

[Phrenic nerve stimulation protects against mechanical ventilation-induced diaphragmatic dysfunction through myogenic regulatory factors].

Objective: To explore the protective effect of electrical stimulation of phrenic nerve on diaphragmatic function during mechanical ventilation. Methods: Forty healthy adult SD rats were randomly divided into 5 groups: blank control group (BC), spontaneous breathing group (SB), electrical stimulation group (ES), mechanical ventilation group (MV), and electrical stimulation and mechanical ventilation group (MS). The rats in each group were treated for 18 h except for the BC group. After treatment, the diaphragm muscle tissue was obtained and the diaphragm contractility including peak-to-peak value(Vpp) and maximum rate of contraction(+ dT/dt max) were measured. Expression of MyoD and myogenin were detected. Results: Except for the ES and the MS groups, there was a significant difference for peak-to-peak value (Vpp) between each 2 groups (P<0.05). Expression levels of MyoD in treatment groups were also significantly different (P<0.05). Expressions of MS(Q-PCR 2(-ΔΔCt) value: 11.66±2.80) and MV(Q-PCR 2(-ΔΔCt) value: 40.89±24.71) in the treatment group were significantly different (P<0.05). The expression of myogenin in the MS and the MV groups were significantly different from those of the BC group(P<0.05), however there was no significant difference between the MS(Q-PCR 2(-ΔΔCt) value: 2.58±2.75) and the MV group(Q-PCR 2(-ΔΔCt) value: 1.63±0.71). Conclusions: Electrical stimulation of the phrenic nerve can change the expression level of MyoD and myogenin to offset mechanical ventilation induced diaphragmatic function damage, and therefore plays a protective effect on the diaphragm.

[Anticoagulant Therapy in Elderly Patients With Atrial Fibrillation].

Is this paper discuss problems of selection of anticoagulant therapy in elderly patients with atrial fibrillation, use of unreasonably low doses of anticoagulants, their risks and adherence to therapy is discussed in the paper.

Optimization and Control of Agent-Based Models in Biology: A Perspective.

Agent-based models (ABMs) have become an increasingly important mode of inquiry for the life sciences. They are particularly valuable for systems that are not understood well enough to build an equation-based model. These advantages, however, are counterbalanced by the difficulty of analyzing and using ABMs, due to the lack of the type of mathematical tools available for more traditional models, which leaves simulation as the primary approach. As models become large, simulation becomes challenging. This paper proposes a novel approach to two mathematical aspects of ABMs, optimization and control, and it presents a few first steps outlining how one might carry out this approach. Rather than viewing the ABM as a model, it is to be viewed as a surrogate for the actual system. For a given optimization or control problem (which may change over time), the surrogate system is modeled instead, using data from the ABM and a modeling framework for which ready-made mathematical tools exist, such as differential equations, or for which control strategies can explored more easily. Once the optimization problem is solved for the model of the surrogate, it is then lifted to the surrogate and tested. The final step is to lift the optimization solution from the surrogate system to the actual system. This program is illustrated with published work, using two relatively simple ABMs as a demonstration, Sugarscape and a consumer-resource ABM. Specific techniques discussed include dimension reduction and approximation of an ABM by difference equations as well systems of PDEs, related to certain specific control objectives. This demonstration illustrates the very challenging mathematical problems that need to be solved before this approach can be realistically applied to complex and large ABMs, current and future. The paper outlines a research program to address them.

Metabonomic analysis of fatty acids in seminal plasma between healthy and asthenozoospermic men based on gas chromatography mass spectrometry.

The mechanism of asthenozoospermia remains unclear. The knowledge of the metabolism of fatty acids in seminal plasma is important and meaningful for the pathological study of asthenozoospermia. We present an optimised assay of extraction and derivatisation followed by GC/MS to analyse metabolites, especially fatty acids, in seminal plasma from healthy and asthenozoospermic men. Eighty-nine peaks including 17 kinds of fatty acids were analysed and identified in the chromatogram. The GC/MS data were analysed using t test, fold change and partial least squares discriminant analysis to explore the potential biomarkers of asthenozoospermia. Seven metabolites in asthenozoospermic group were found to be significantly different from those in the normal group (with p < .05, fold change >1.2 and variable importance for projection >1). Of which, high levels of oleic acid and palmitic acid in seminal plasma from asthenozoospermic men may indicate a membrane metabolism disorder in spermatozoa and the lack of valine in the asthenozoospermic group may contribute to poor sperm motility. The results may facilitate the understanding of the role of fatty acids and amino acids in asthenozoospermia and provide solid foundation for further pathological study of asthenozoospermia.

[Treatment of complicated intra-articular distal radius fractures with extended flexor carpi radialis approach].

OBJECTIVE: To discuss the effect of treatment of complicated intra-articular distal radius fractures with extended flexor carpi radialis approach. METHODS: A retrospective analysis of 38 cases with fresh complicated intra-articular distal radius fractures treated by using extended flexor carpi radialis approach in our hospital from October 2012 to March 2015, with 25 males and 13 females. The average age was (52.76±8.62) years (32-64 years). The average time to surgery was (5.42±1.91) d (3-10 d), with left wrist 17 cases and right wrist 21 cases. All the patients were with C3 distal radius fractures according to Association for the Study of Internal Fixation (AO/ASIF) classification. The follow-up was conducted 1, 2, 3, 6, and 12 months after operation, including AP and lateral X-ray, wrist extension and flexion, radial deviation and ulnar deviation, forearm pronation and supination, and grip strength. At the end of 6 and 12 months after operation, all the patients were evaluated by using the modified Garland-Werley score and patient rated wrist evaluation (PRWE). RESULTS: All the patients got good bone union, and their follow-up time was more than 12 months. The average follow-up time was (16.37±2.85) months (12-22 months). The score of modified Garland-Werley evaluation 6 months postoperation was 5.37±2.82, excellent and good rate was 84.21%, the score of modified Garland-Werley evaluation 12 months postoperation was 5.03±2.60, excellent and good rate was 86.84%. The score of PRWE 6 months postoperation was 15.82±8.38, the score of PRWE 12 months postoperation was 12.17±7.58. CONCLUSION: The extended flexor carpi radialis approach is effective for the treatment of complicated intra-articular distal radius fractures and can avoid the complications of volar and dorsal combination approach.

[Value of heart rate as an optimum index in evaluating physical labor intensity].

Objective: To investigate the possibility of heart rate as an optimum index for evaluating physical labor intensity. Methods: From September to October, 2015, a total of 111 male young adults were selected as study subjects. A cycle ergometer was used for exercise at different intensities (20, 40, 60, 80, 100, 120, 140, 160, and 180 W) , and the exercise at each intensity lasted for 6 minutes. The subjects wore the K4b2 portable cardiopulmonary function testing instrument for the real-time monitoring of heart rate (HR) , pulmonary ventilation volume (Ve) , oxygen consumption (VO(2)) , and energy metabolic rate (E) . The origin software was used for correlation and regression analyses of HR, Ve, VO(2), and E collected at different intensities to establish Ve-HR, VO(2)-HR, and E-HR regression equations. Results: At different intensities, HR was positively correlated with Ve, VO(2), and E (r=0.8985, 0.8733, and 0.8973, all P<0.01) . There was a significant difference in the R(2) value of Ve-HR, VO(2)-HR, and E-HR regression equations (R(2)=0.8070, 0.7625, and 0.8049, all P <0.01) . The validation results showed that there was no significant difference between the calculated values and the measured ones (P>0.05) . Conclusion: HR can replace Ve, VO(2), and E and be used as an optimum index for evaluating physical labor intensity.

The accuracy of circulating microRNA-21 in the diagnosis of colorectal cancer: a systematic review and meta-analysis.

AIM: The accuracy and clinical value of circulating microRNA-21 (miR-21) were assessed as a novel diagnostic biomarker of colorectal cancer (CRC). METHOD: Medline/PubMed, EMBASE, the Cochrane Library databases and grey literature (Google scholar; British Library) were searched up to 29 September 2014 for eligible studies of the association between blood-based miR-21 and a diagnosis of CRC. Quality Assessment of Diagnostic Accuracy Studies (QUADAS) was employed to assess the quality of the included studies by two investigators. Stata12.0 and Meta-DiSc1.4 software were applied to test the heterogeneity using Cochran's Q test and I(2) statistics and to perform the meta-analysis. RESULTS: Seven studies with 676 CRC patients and 417 controls were included in the meta-analysis. All were of high quality (QUADAS scores 12 or 13). For miR-21, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio to predict CRC were 75% [95% confidence interval (CI) 63-83%], 84% (95% CI 79-87%), 4.61 (95% CI 3.38-6.29), 0.30 (95% CI 0.20-0.46) and 16.89 (95% CI 7.56-37.73) after using a random-effects model analysis. The area under the summary receiver operating characteristic curve was 0.86 (95% CI 0.83-0.89). CONCLUSION: The results suggest that circulating miR-21 is a biomarker with moderate sensitivity and specificity for CRC.

Population pharmacokinetics of rifampin in the treatment of Mycobacterium tuberculosis in Asian elephants.

The objective of this study was to develop a population pharmacokinetic model for rifampin in elephants. Rifampin concentration data from three sources were pooled to provide a total of 233 oral concentrations from 37 Asian elephants. The population pharmacokinetic models were created using Monolix (version 4.2). Simulations were conducted using ModelRisk. We examined the influence of age, food, sex, and weight as model covariates. We further optimized the dosing of rifampin based upon simulations using the population pharmacokinetic model. Rifampin pharmacokinetics were best described by a one-compartment open model including first-order absorption with a lag time and first-order elimination. Body weight was a significant covariate for volume of distribution, and food intake was a significant covariate for lag time. The median Cmax of 6.07 µg/mL was below the target range of 8-24 µg/mL. Monte Carlo simulations predicted the highest treatable MIC of 0.25 µg/mL with the current initial dosing recommendation of 10 mg/kg, based upon a previously published target AUC0-24/MIC > 271 (fAUC > 41). Simulations from the population model indicate that the current dose of 10 mg/kg may be adequate for MICs up to 0.25 µg/mL. While the targeted AUC/MIC may be adequate for most MICs, the median Cmax for all elephants is below the human and elephant targeted ranges.

Seedling performance of Phragmites australis (Cav.) Trin ex. Steudel in the presence of arbuscular mycorrhizal fungi.

AIMS: Arbuscular mycorrhizal (AM) fungus-plant symbiosis may induce morphological, physiological and/or biochemical changes in the host plants. This study was performed to investigate the effects of AM fungi on Phragmites australis (Cav.) Trin ex. Steudel. METHODS AND RESULTS: Funnelliformis mosseae and Rhizophagus irregularis were chosen as inocula, and detailed attributes related to seedling performance (from seed to five-leaf stage), rhizospheric conditions and micro-organisms were measured and compared. Both of the chosen AM fungal inocula accelerated seed germination and enhanced growth and development, especially in the underground tissues, of seedlings. Specifically, AM fungal colonization improved the photosynthetic efficiency, rhizospheric soil respiration and absorption of certain nutrients in Ph. australis seedlings as well as the rhizospheric microbial metabolic activity and richness in different extents. However, the decreased metabolic diversity suggested that the effects of AM fungi on rhizospheric microbial communities are specific and selective. CONCLUSIONS: As a whole, F. mosseae showed greater improvements in the performance of Ph. australis seedlings than R. irregularis. In addition, the potential applications of AM fungi as a 'bio-accelerator', 'biofortifier', and 'bio-enhancer' in phyto-rhizoremediation have been discussed. SIGNIFICANCE AND IMPACT OF THE STUDY: The main findings could preliminarily reveal the mechanisms behind AM fungus-plant symbioses and could be referred to when optimizing combined phyto-rhizoremediation before practical applications take place.

Three novel single nucleotide polymorphisms of the 3-hydroxy-3-methylglutaryl coenzyme A reductase gene associated with egg-production in chicken.

Different single-strand conformation polymorphism (SSCP) patterns of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) gene amplified by six pairs of primers were sequenced. Comparisons among the six nucleotide sequences of three genotypes revealed three base substitutions (G-789-A, C-937-G, and A-2316-C) in the HMGCR gene. The genotypes of single nucleotide polymorphism 1 (SNP1) and SNP3 were significantly associated with the number of eggs (P < 0.01), and the different genotypes of SNP2 did not significantly influence the number of eggs. The genotypes of all three SNPs were not related to the hatching rate of fertilized eggs (P > 0.05). Of the three SNPs of the HMGCR gene, those genotypes with lower plasma very low-density lipoprotein (VLDL) concentrations had higher egg production. The 300-day egg production of the six studied haplotypes showed three levels (P < 0.01). The ADE and ACE haplotypes showed lower egg production than the other haplotypes. The ADE haplotype had the highest plasma VLDL concentration, and the ACE haplotype had the lowest plasma VLDL concentration. We concluded that specific variants of the HMGCR gene are associated with chicken egg production, and haplotypes with higher and lower plasma VLDL concentrations showed lower egg production than other haplotypes.

Foetal and neonatal outcomes in first-trimester pregnant women exposed to abdominal or lumbar radiodiagnostic procedures without administration of radionucleotides.

BACKGROUND/AIM: Little is known about exposures to low radiation doses in the first trimester of pregnancy and deterministic adverse effects in the offspring, and risks are extrapolated from catastrophic events or from exposures to radiotherapy. The study aimed to assess the foetal and neonatal outcomes of pregnant women exposed to radiodiagnostic procedures with abdominal or lumbar irradiation. METHODS: In a prospective cohort design, we studied the foetal and neonatal outcomes in 115 singleton pregnant women who required abdominal or lumbar radiodiagnostic procedures without the administration of radionucleotides, and in 527 age-matched (± 2 years) control pregnant women. RESULTS: In the exposed group, lumbar spine radiography (33.9%), plain abdominal radiography (16.5%) and upper gastrointestinal tract radiography with abdominal irradiation (15.7%) were the most common radiodiagnostic procedures. Major congenital malformations were identified in two (1.9%) babies born in the exposed group and in two (0.4%) babies born in the control group (odds ratio = 4.7; 95% confidence interval 0.7-33.6; P = 0.15). The rest of the foetal and neonatal outcomes was similar in the two groups except by a marginally higher rate of admissions to the neonatal intensive care unit among babies born to exposed women (odds ratio = 2.9; 95% confidence interval 1.0-9.4; P = 0.06). CONCLUSION: Our results indicate that X-ray and computed tomography scan exposure involving abdominal irradiation without the administration of radionucleotides is not associated with adverse foetal and neonatal deterministic outcomes. Efforts are required to reduce the use of radiodiagnostic procedures for general check-ups in childbearing age women.