Post-Left Atrium Space Index in Fetuses With Total Anomalous Pulmonary Venous Connection and Other Congenital Heart Diseases.

OBJECTIVES: We aimed to explore the value of the post-left atrium space (PLAS) index in the diagnosis of total anomalous pulmonary venous connection (TAPVC) and the effect of other congenital heart diseases on the PLAS index in the fetus. METHODS: The PLAS index of 69 fetuses with TAPVC was analyzed retrospectively. Approximately 252 healthy fetuses were randomly selected as controls, and 110 cases of intracardiac malformations were randomly selected for comparison. The PLAS index was defined as the ratio of the left atrium-descending aorta distance divided by the descending aorta diameter from the 4-chamber view in the end-systolic phase. RESULTS: There were no significant differences in the PLAS index among the 3 groups of isolated TAPVC subtypes (P > .05), or among the isolated TAPVC group and the simple and complex cardiac anomaly groups (P > .05). Compared with the control group, the PLAS index of the TAPVC group was significantly increased (P < .001). The PLAS index was significantly higher in the TAPVC group than in hypoplastic left heart syndrome, endocardial cushion defect, conotruncal defect, and ventricular septal defect groups (P < .05). The PLAS indices of the hypoplastic left heart syndrome, endocardial cushion defect, and conotruncal defect groups were all higher than that of the control group (P < .05). There was no significant difference in the PLAS index between the ventricular septal defect and control groups (P > .05). CONCLUSIONS: The PLAS index is a sensitive parameter for the diagnosis of fetal TAPVC. There were no significant differences in the PLAS index among different TAPVC types. Complex intracardiac anomalies have an influence on the PLAS index.

Left and right ventricular function detection and myocardial deformation analysis in heart transplant patients with long-time follow-ups.

OBJECTIVE: We try to investigate whether the values of longitudinal strain present differences between the left and right ventricles in long-time follow-ups after heart transplantation (HTx) with dynamic changes in function. METHODS AND RESULTS: Follow-up transthoracic echocardiography was performed in 1- and 3-month and 1- and 5-year follow-ups in 50 "healthy" HTx patients and compared with 26 control subjects. The left ventricle with preserved ejection fraction evaluated by biplane Simpson (control group [CG] vs HT; P > .05) had an obvious reduction in global (CG: -20.49 ± 2.38 vs heart transplant 1 month [HT1m]: -13.06 ± 2.86, heart transplant 3 month [HT3m]: -13.61 ± 2.61, heart transplant 1 year [HT1y]: -13.69 ± 4.56, heart transplant 5 year [HT5y]: -14.41 ± 4.54; P < .001) and horizontal segmental (basal, mid, apical) (P < .001) together with chamber segmental (apical 4-chamber, apical 3-chamber, apical 2-chamber) (P < .001) average strain values. The right ventricle with reduced ventricular function measured by tissue Doppler imaging S' and tricuspid annular plane systolic excursion had a more distinctive reduction in global (CG: -24.53 ± 4.20 vs HT1m: -12.94 ± 5.03, HT3m: -13.68 ± 4.35, HT1y: -14.95 ± 7.50, HT5y: -15.20 ± 6.15; P < .001) with segmental lateral (P < .001) strain values. There were not any significant changes between 1- and 3-month follow-ups of all the values (P > .05). But it could be seen that values increased in 1- and 5-year follow-ups compared with the baseline of 1- and 3-month follow-ups (P < .05). The global and segmental strain of the right ventricle decreased more than that of the left ventricle in all HTx groups, and the strain values were decreased in the HTx groups compared with the CG, with the global decreased change rates being 11%, 10%, 6%, and 8%, respectively. CONCLUSIONS: The strain values decreased after HTx and almost remained stable in the long-time follow-ups. Compared with the CG in both ventricles, they were with preserved or reduced functions. In addition, the deformation values of the right ventricle decreased more than those of the left.

Association between magnetic resonance imaging of carotid artery and coronary stenosis detected by computed tomography angiography.

OBJECTIVE: To investigate the correlation between carotid artery stenosis (CAS) measured by magnetic resonance imaging (MRI) and the coronary stenosis (CS) determined by computed tomography angiography (CTA). METHODS: In this prospective study, 42 subjects diagnosed with coronary artery disease (CAD) underwent MRI and CTA examinations. The severity degree and number of CAS, the score, detection rate and type of carotid plaque, and also the severity degree and number of CS were assessed. Spearman's rank correlation test was used to evaluate the correlation between CAS and CS. RESULTS: CS was detected in 42 (100%) subjects, while CAS was detected in 36 (85.7%) subjects. Distribution of CAS severity grades in multiple-vessel group was significantly different from other groups, which with more moderate and severe stenosis (p < 0.05). A positive and significant correlation between the CAS severity and CS severity (r = 0.612, p < 0.05), and the number of involved coronary vessels (r = 0.572, p < 0.05) were observed, respectively. Both detection rate (r = 0.587, p < 0.05) and score (r = 0.735, p < 0.05) of carotid plaque showed a good correlation with the number of involved coronary vessels. After carotid MRI, 71 carotid plaques were detected in 42 subjects, with an incidence rate of 9.9% in subjects with mild CS, 18.3% in moderate CS and 71.8% in severe CS. CONCLUSION: Correlation between CAS measured by MRI and CS determined by CTA was identified in present study. These results indicated that the non-invasive CAS evaluation employing the MRI may be clinically useful for the assessment of CS.

Left ventricular dyssynchrony in coronary artery disease patients without regional wall-motion abnormality: Correlation with Gensini score.

OBJECTIVES: Our study investigated left ventricular dyssynchrony (LVD) in coronary artery disease (CAD) patients without regional wall-motion abnormality (RWMA) by three-dimensional echocardiography (3-DE) and explored the relationship between LVD and severity of CAD as assessed by the Gensini score (GS). METHODS: Sixty-one patients with a confirmed diagnosis of CAD by coronary angiography (CAG) were enrolled. We quantified LVD parameters, including the left ventricular segments (16, 12, and 6) standard deviation of the time to minimum systolic volume (TmsvSD-16, TmsvSD-12, and TmsvSD-6) and the systolic dyssynchrony index in regions 16, 12, and 6 (16R-SDI, 12R-SDI, 6R-SDI) using 3-DE. The severity of coronary atherosclerotic lesions was evaluated by the GS system on the basis of CAG findings. We further divided all patients into three groups according to the tertiles of GS: low-GS ≤20, mid-GS >20 and ≤48, and high-GS >48. The differences of LVD values among the three groups were compared, and the associations between LVD parameters and GS were analyzed. RESULTS: Coronary artery disease patients demonstrated increased LVD parameters compared with healthy controls. TmsvSD12, 16R-SDI, and 6R-SDI were prolonged in the high-GS group compared with the low- and mid-GS groups. 16R-SDI was positively correlated with the GS, and multivariate regression analysis showed that 16R-SDI was an independent predictor of the GS. 16R-SDI above 10.7% had a sensitivity of 84.21% and a specificity of 92.86% for identifying high-GS. CONCLUSION: Three-dimensional echocardiography is a noninvasive technique to detect LVD in non-RWMA CAD patients, and the parameter 16R-SDI was significantly correlated with CAD severity.

A Dynamic Model for Predicting Outcome in Patients with HBV Related Acute-On-Chronic Liver Failure.

INTRODUCTION AND AIM: Accurately predicting the prognosis of individual patient is crucial in the management of ACLF. We aimed to establish a specific prognostic model for HBV-related ACLF patients treated with nucleoside analog (NA). MATERIAL AND METHODS: We prospectively collected 205 ACLF cases diagnosed according to the APASL criteria. A dynamic prognostic model based on APASL criteria was established and validated. To demonstrate that the model is also applicable to those within EASL criteria, we divided the patients into two groups: met APASL criteria only (group A, n = 123); met both APASL and EASL criteria (group B, n = 82). Its prognostic accuracy was also compared with chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score in group B. RESULTS: The model is: R = 0.94 x Bilirubin + 0.53 x evolution of Bilirubin - 0.45 x PT-A - 0.22 x evolution in PT-A -0.1 x PLT + 10 x anti-HBe. The area under receiver operating characteristic curve (AUC) of the model for predicting 90-day mortality was 0.86, which was significantly higher than that of model for end stage liver disease(MELD), MELD-Na, CLIF-SOFA, ΔMELD (7d) and ΔMELD-Na (7d), ΔCLIF- SOFA(7d) (all p < 0.01). The AUC of our model in the validation group was 0.79 which was superior to MELD (0.45) CLIF-SOFA (0.53) score in group B patients (p < 0.01). CONCLUSION: In conclusion, the model was superior to the conventional methods in predicting the outcomes of patients with HBV related ACLF treated with NA. It is the first description of a novel prognostic model using consecutive data in patients with HBV-induced acute-on-chronic liver failure (ACLF) treated by nucleoside analogs.

Assessment of Left Ventricular Myocardial Viability by 3-Dimensional Speckle-Tracking Echocardiography in Patients With Myocardial Infarction.

OBJECTIVES: To determine whether 3-dimensional (3D) speckle-tracking echocardiography could provide a new way to assess myocardial viability in patients with myocardial infarction (MI). METHODS: Forty-five patients with MI underwent routine echocardiography, 2-dimensional (2D) speckle-tracking echocardiography, and 3D speckle-tracking echocardiography. Radionuclide myocardial perfusion/metabolic imaging was used as a reference standard to define viable and nonviable myocardia. RESULTS: Among 720 myocardial segments in 45 patients, 368 showed abnormal motion on routine echocardiography; 204 of 368 were categorized as viable on single-photon emission computed tomography/positron emission tomography (SPECT/PET), whereas 164 were defined as nonviable; 300 normal segments on SPECT/PET among 352 segments without abnormal motion on routine echocardiography were categorized as a control group. The radial, longitudinal, 3D, and area strain on 3D speckle-tracking echocardiography had significant differences between control and nonviable groups (P < .001), whereas none of the parameters had significant differences between control and viable groups. There were no significant differences in circumferential, radial, and longitudinal peak systolic strain from 2D speckle-tracking echocardiography between viable and nonviable groups. Although there was no significant difference in circumferential strain between the groups, radial and longitudinal strain from 3D speckle-tracking echocardiography decreased significantly in the nonviable group. Moreover, 3D and area strain values were lower in the nonviable segments than the viable segments. By receiver operating characteristic analysis, radial strain from 3D speckle-tracking echocardiography with a cutoff of 11.1% had sensitivity of 95.1% and specificity of 53.4% for viable segments; longitudinal strain with a cutoff of 14.3% had sensitivity of 65.2% and specificity of 65.7%; 3D strain with a cutoff of 17.4% had sensitivity of 70.6% and specificity of 77.2%; and area strain with a cutoff of 23.2% had sensitivity of 91.5% and specificity of 82.8%. CONCLUSIONS: Three-dimensional speckle-tracking echocardiography might have potential for detection of myocardial viability in patients with cardiac dysfunction due to MI.

Summary of the best evidence for prehabilitation management of patients with non-small cell lung cancer.

Objective: This study adopts an evidence-based methodology to establish a comprehensive theory foundation for preoperative prehabilitation management in non-small cell lung cancer (NSCLC) patients. Methods: A systematic literature review linked to prehabilitation management for NSCLC patients was conducted, utilizing reputable databases such as UpToDate, BMJ Best Practice, UK NICE, SIGN, GIN, Joanna Briggs Institute Library, Cochrane Library, Web of Science, Embase, OVID evidence-based database, PubMed, Chinese Wanfang database, CNKI, CBM, ATS, BTS, AACVPR, and EACTS. The search encompassed articles, including clinical decision-making, guidelines, evidence summaries, expert consensuses, and systematic reviews, from the inception of databases up to March 31st, 2023. Two researchers performed quality assessment of the literature and subsequent evidence extraction. Results: Nineteen articles were included, comprising five guidelines, three expert consensuses, seven systematic reviews, and four randomized controlled trials. A total of 41 pieces of evidence were summarized, addressing key aspects such as the multidisciplinary team, appropriate patient population, prehabilitation modes, timing of prehabilitation, prehabilitation assessment, prehabilitation content, quality control, and effectiveness evaluation. Conclusions: The synthesis of the best evidence for prehabilitation management in NSCLC patients provides a solid evidence-based foundation for its implementation. It is recommended that healthcare professionals conduct thorough patient evaluations, optimize and integrate medical resources, and collaboratively engage in interdisciplinarity efforts to develop and implement personalized and multimodal prehabilitation plans.

Global myocardial work in coronary artery disease patients without regional wall motion abnormality: Correlation with Gensini-score.

BACKGROUND: Early detection of coronary atherosclerotic diseases (CAD) without regional wall motion abnormality (RWMA) is important for improving the outcome of cardiovascular events. Global myocardial work (GMW), including global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global myocardial work efficiency (GWE), offer comprehensive quantitative assessment of myocardial function in CAD. HYPOTHESIS: We hypothesized that GMW could provide incremental value in detecting CAD without RWMA. METHODS: One hundred and twenty-four patients referred for coronary angiography (CAG) without resting RWMA were enrolled in this study. Global longitudinal strain (GLS), GWI, GCW, GWW, GWE were quantified. The severity of coronary lesions was evaluated by Gensini score (GS) based on CAG. We further divided CAG-confirmed CAD patients into three subgroups according to the tertiles of GS: low 0 < GS ≤ 17, mid 17 < GS ≤ 38, and high GS > 38. RESULTS: Compared with control, CAD patients showed decreased GLS, GWE, GWI, GCW but an increased GWW. Compared to low-GS group, GWW was increased in the mid-GS group. GLS, GWE, GWI and GCW were decreased in the high-GS group while GWW was increased. Receiver operator characteristic curve analysis demonstrated that GWE was the most powerful predictor of high-GS and was superior to GLS. GWE under 92.0% had the optimal sensitivity and specificity for identifying high-GS. CONCLUSION: The proposed GWE, which outperformed the conventional GLS, could be considered as a potential predictive indicator to help to detect severe coronary disease in non-RWMA CAD patients.

[Viable myocardium evaluation by two dimensional speckle tracking imaging combined with adenosine stress echocardiography].

OBJECTIVE: Regional left ventricular (LV) function could be detected by measuring peak-systolic strain by speckle tracking imaging (STI). We evaluated the value of STI combined with adenosine stress echocardiography on assessing myocardial viability in patients with myocardial infarction (MI). METHODS: Two dimensional echocardiography was performed at rest and after adenosine stress echocardiography (infused at 140 µg×kg(-1)×min(-1) over a period of 6 min) in 39 stable patients with previous MI. Peak-systolic (Speak-sys) circumferential strain, radial strain and longitudinal strain were assessed by STI. Radionuclide myocardial perfusion/metabolic imaging served as the "gold standard" to detection of myocardial viability. RESULTS: (1) There were 215 viable and 153 non-viable regions among 368 abnormal motion segments out of 624 segments in 39 MI patients according to radionuclide imaging results. (2) Speak-sys was similar between viable and nonviable myocardium at rest (all P > 0.05). After adenosine infusion, radial Speak-sys [(37.98 ± 5.45)% vs. (30.22 ± 5.47)%], longitudinal Speak-sys [(-23.71 ± 4.53)% vs. (-17.52 ± 4.34)%] increased significantly (P < 0.05)in viable segments compared to baseline levels and were significantly higher than in nonviable segments radial Speak-sys [(37.98 ± 5.45)% vs. (30.12 ± 5.37)%] and longitudinal Speak-sys [(-23.71 ± 4.53)% vs. (-16.95 ± 4.62)%] (P < 0.05), while remained unchanged in nonviable segments before and after adenosine infusion. Circumferential Speak-sys was similar before and after adenosine infusion in both viable and nonviable segments (all P > 0.05). (3) Delta radial strain change > 9.8% has a sensitivity of 82.3% and a specificity of 81.1% whereas a delta change of longitudinal strain > 16.5% has a sensitivity of 83.5% and a specificity of 92.3% for detecting viable segments. CONCLUSIONS: Speckle tracking imaging combined with adenosine stress echocardiography could serve as a new and reliable method of assessing myocardial viability.

Spider venom-derived peptide JZTX-14 prevents migration and invasion of breast cancer cells via inhibition of sodium channels.

Nav1.5 channel is crucial for the proliferation and migration of breast cancer cells. In this study, we investigated the anticancer effect of JZTX-14, a natural peptide considered an effective antagonist of Nav1.5. First, we successfully isolated and purified the 31 amino acid peptide JZTX-14 containing three pairs of disulfide bonds from spider venom and synthesised JZTX-14 by solid phase synthesis. We then predicted their physiochemical properties and structures in the peptide database. Further, we investigated the effects of natural and synthetic JZTX-14 on the proliferation and migration of MDA-MB-231 breast cancer cells via modulation of sodium current through the Nav1.5 channel. The results showed that both synthetic and natural JZTX-14 inhibited Nav1.5 currents, indicating the successful synthesis of JZTX-14. However, JZTX-14 did not affect MDA-MB-231 cell proliferation but inhibited its migration. Transcriptome analysis revealed that JZTX-14 downregulated S100A4 and FBXO2 and upregulated SERPINB2 in MDA-MB-231 cells. Western blot analysis demonstrated an increased level of the epithelial marker, E-cadherin, and decreased levels of the mesenchymal markers, N-cadherin and vimentin, and matrix metalloproteinase (MMP2), indicating the possible underlying mechanism of the inhibition of MDA-MB-231 cell migration by JZTX-14. This study provides a new target for inhibiting breast cancer metastasis and identifies a potent natural peptide for treating Triple-negative breast cancer.

An effective fingerprint orientation field estimation method using differential values of grayscale intensity.

Fingerprint orientation field (OF) estimation is important for basic fingerprint image processing and impacts the accuracy of fingerprint image enhancements, such as Gabor filters. In this article, we introduce an OF estimation algorithm based on differential values of grayscale intensity and examine the accuracy and reliability of the proposed algorithm by applying it to fingerprint images processed using Gaussian blurring and the Gaussian white noise process. The experimental results indicate that the OF estimation reliability of the proposed algorithm is higher than the gradient-based method and the power spectral density (PSD) based method in low quality fingerprints. The proposed algorithm is especially useful in noisy fingerprint images, where the OF estimation reliability of the algorithm is 6.46% and 32.93% higher than the gradient-based method and the PSD-based method, respectively.

The Enhanced Thermal Stability of (Mg0.95Ni0.05)2TiO4 Dielectric Ceramics Modified by a Multi-Phase Method.

The thermal stability of (Mg0.95Ni0.05)2TiO4 dielectric ceramics has been improved by mixing with CaTiO3 phases owing to higher positive temperature coefficients. The pure (Mg0.95Ni0.05)2TiO4 and the mixture phase systems of CaTiO3-modified (Mg0.95Ni0.05)2TiO4 were verified by XRD diffraction patterns to ensure the crystallite of different phases. The microstructures of the CaTiO3-modified (Mg0.95Ni0.05)2TiO4 were observed by SEM and EDS to investigate the relation between element ratios and grains. As a result, it can be seen that the thermal stability of the CaTiO3-modified (Mg0.95Ni0.05)2TiO4 can be effectively enhanced, compared with the pure (Mg0.95Ni0.05)2TiO4. Moreover, the radio frequency dielectric performances of CaTiO3-modified (Mg0.95Ni0.05)2TiO4 dielectric ceramics are strongly dependent upon the density and the morphology of the specimens. The champion sample with the ratio of (Mg0.95Ni0.05)2TiO4 and CaTiO3 of 0.92:0.08 showed an εr value of 19.2, an Qf value of 108,200 GHz, and a τf value of -4.8 ppm/°C, which may encourage (Mg0.95Ni0.05)2TiO4 ceramics to broaden the range of novel applications and match the requirements of 5G or next-generation communication systems.

Disrupting the intermolecular self-association of Itk enhances T cell signaling.

The Tec family tyrosine kinase (Itk), is a key component of the TCR signaling pathway. Biochemical studies have shown that Itk activation requires recruitment of Itk to the membrane via its pleckstrin homology domain, phosphorylation of Itk by the Src kinase, Lck, and binding of Itk to the SLP-76/LAT adapter complex. However, the regulation of Itk enzymatic activity by Itk domain interactions is not yet well understood. In this study, we show that full-length Itk self-associates in an intermolecular fashion. Using this information, we have designed an Itk variant that exhibits reduced self-association but maintains normal binding to exogenous ligands via each of its regulatory domains. When expressed in insect cells, the Itk substrate phospholipase Cgamma1 is phosphorylated more efficiently by the Itk variant than by wild-type Itk. Furthermore, expression of the Itk variant in primary murine T cells induced higher ERK activation and increased calcium flux following TCR stimulation compared with that of wild-type Itk. Our results indicate that the Tec kinase Itk is negatively regulated by intermolecular clustering and that disruption of this clustering leads to increased Itk kinase activity following TCR stimulation.

Clinic value of two-dimensional speckle tracking combined with adenosine stress echocardiography for assessment of myocardial viability.

BACKGROUND: To evaluate whether myocardial strain under adenosine stress calculated from two-dimensional echocardiography by automatic frame-by-frame tracking of natural acoustic markers enables objective description of myocardial viability in clinic. METHODS AND RESULTS: Two-dimensional echocardiography and two-dimensional speckle tracking imaging (2D STI) at rest were performed first and once again after adenosine was infused at 140 ug/kg/min over a period of 6 minutes in 36 stable patients with previous myocardial infarction. Then radionuclide myocardial perfusion/metabolic imaging served as the "gold standard" to define myocardial viability was given in all patients within 1 day. Two-dimensional speckle tracking images were acquired at rest and after adenosine administration. An automatic frame-by-frame tracking system of natural acoustic echocardiographic markers was used to calculate 2D strain variables including peak-systolic circumferential strain (CS(peak-sys)), radial strain (RS(peak-sys)), and longitudinal strain (LS(peak-sys)). Those segments with abnormal motion from visual assessment of two-dimensional echocardiography were selected for further study. As a result, 126 regions were viable whereas 194 were nonviable among 320 abnormal motion segments in 36 patients according to radionuclide imaging. At rest, there were no significant changes of 2D strain between the viable and nonviable myocardium. After adenosine administration (140 ug/kg/min), CS(peak-sys) had a little change of the viable myocardium while RS(peak-sys) and LS(peak-sys) increased significantly compared with those at rest. In nonviable group, CS(peak-sys), RS(peak-sys), and LS(peak-sys) had no significant changes during adenosine administration. After adenosine administration, RS(peak-sys) and LS(peak-sys) in viable group increased significantly compared with nonviable group. Obtained strain data were highly reproducible and affected in small intraobserver and interobserver variabilities. A change of radial strain more than 9.5% has a sensitivity of 83.9% and a specificity of 81.4% for viable whereas a change of longitudinal strain more than 14.6% allowed a sensitivity of 86.7% and a specificity of 90.2%. CONCLUSIONS: 2D STI combined with adenosine stress echocardiography could provide a new and reliable method to identify myocardium viability.

[Development of glipizide push-pull osmotic pump controlled release tablets by using expert system and artificial neural network].

The purpose of this study is to develop glipizide push-pull osmotic pump (PPOP) tablets by using a formulation design expert system and an artificial neural network (ANN). Firstly, the expert system for the formulation design of osmotic pump of poor water-soluble drug was employed to design the formulation of glipizide PPOP, taking the dissolution test results of Glucotrol XL as the goal. Then glipizide PPOP was prepared according to the designed formulations and the in vitro dissolution was carried out. And in vivo evaluation was carried out between the samples which were similar to Glucotrol XL and the Glucotrol XL in Beagle dogs. The range of the factors of formulation and procedure, which could influence the drug release, was optimized using artificial neural network. Finally, the design space was found. It was found that the target formulation which was similar to Glucotrol XL in dissolution test could be obtained in a short period by using the expert system. The samples which were similar to Glucotrol XL were bio-equivalent to the Glucotrol XL in Beagle dogs. The design space of the key parameter coating weight gain was 9.5%-12.0%. It could be concluded that a well controlled product of glipizide PPOP was developed since the dissolution test standard of our product was more strict than that of Glucotrol XL.

Experimental results and mathematical formulation of non-spinning stone-skipping process.

Following a previously published paper in studying stone-skipping processes, detailed experimental figures are revealed in this paper. A mathematical model is also provided to explain the observed phenomena and measured data. The model separates the skipping process into several stages. It emphasizes, in particular, a hitting stage and a sliding stage, and also includes capillary-gravity wave resistance in its formulation. During these two stages, scale analysis is applied first to evaluate the relative importance among various forces acting on the stone. After reasonable simplification, a numerical algorithm is established to depict motion of the stone starting from its first hit of water to final sink. The total number of skips under specified initial throwing conditions can be predicted accordingly. The agreement between the analytical and experimental results indicates the applicability of the proposed model.

[Design push-pull osmotic pump tablets of famotidine based on an expert system for the formulation design of osmotic pump of poor water-soluble drug].

The purpose of this study is to design push-pull osmotic pump (PPOP) tablets of famotidine using the expert system for the formulation design of osmotic pump of poor water-soluble drug which had been established by the authors. Firstly, the parameters which were requisite of the system input were obtained from literatures and experimental tests. Then the parameters were input into the system, and the program was run. The system displayed the designed formulations sequential. Finally, famotidine PPOP was prepared according to the designed formulations and the in vitro dissolution was carried out. It was found out that the target formulation of famotidine PPOP which could release for 24 hours was obtained in a very short period. Meanwhile, the practicability of the established expert system was proved.

[Improved therapeutic effectiveness by combining recombinant human RhoB with low-dose cisplatin in human lung cancer in nude mice].

OBJECTIVE: To determine the antitumor effects of the recombinant human RhoB with low-dose cisplatin in lung carcinoma models. METHODS: The pVITRO2-RhoB recombinant was constructed and transfected into A549 cells. Its expression and the inhibition effect to the A549 cells were observed models. A549 lung carcinoma mice were treated with either RhoB or cisplatin or both agents together. And the change of tumor size, the survive time of mice, the apoptosis of tumor were also observed. RESULTS: The pVITRO2-RhoB recombinant was constructed successfully. This recombinant could inhibit the growth and promote the apoptosis of A594 in vitro. Mice treated with RhoB or low-dose cisplatin treatment individually resulted in tumor inhibition to a certain extent. Mice treated with combination of RhoB and low-dose cisplatin resulted in synergistic antitumor activity with more effective tumor inhibition (P < 0.05) and longer survival (P < 0.05). TUNEL analysis of tumors exhibited that RhoB in combination with cisplatin led to the increased rate of apoptosis (P < 0.05). CONCLUSION: Our data demonstrated that RhoB could increase the sensitivity of lung carcinoma to cisplatin, resulting in enhanced anti-tumor activity. These results suggest that combination with recombinant human RhoB with chemotherapy drugs may be an effective approach in the treatment of lung carcinoma.

Clinical utility of a serum biomarker panel in distinguishing prostate cancer from benign prostate hyperplasia.

Prostate-specific antigen (PSA) screening for prostate cancer (PCa) is limited by the lack of specificity but is further complicated in the benign prostatic hyperplasia (BPH) population which also exhibit elevated PSA, representing a clear unmet need to distinguish BPH from PCa. Herein, we evaluated the utility of FLNA IP-MRM, age, and prostate volume to stratify men with BPH from those with PCa. Diagnostic performance of the biomarker panel was better than PSA alone in discriminating patients with negative biopsy from those with PCa, as well as those who have had multiple prior biopsies (AUC 0.75 and 0.87 compared to AUC of PSA alone 0.55 and 0.57 for patients who have had single compared to multiple negative biopsies, respectively). Of interest, in patients with PCa, the panel demonstrated improved performance than PSA alone in those with Gleason scores of 5-7 (AUC 0.76 vs. 0.56) and Gleason scores of 8-10 (AUC 0.74 vs. 0.47). With Gleason scores (8-10), the negative predictive value of the panel is 0.97, indicating potential to limit false negatives in aggressive cancers. Together, these data demonstrate the ability of the biomarker panel to perform better than PSA alone in men with BPH, thus preventing unnecessary biopsies.

A QuikChange-like method to realize efficient blunt-ended DNA directional cloning and site-directed mutagenesis simultaneously.

Here we present a QuikChange-like method to efficiently realize blunt-ended DNA cloning and conveniently introduce a site-directed mutation to recombinant plasmid at the same time. After blunt-ended DNA ligation and transformation, the plasmid DNA mixture is extracted from pooled transformants and directly used as template for PCR amplification with a pair of complementary mutagenic primers. With this method, sam1 gene was inserted into pUC19 vector by blunt-end ligation, and a unique restriction site Spe I was introduced to the recombinant plasmid at the same time. The randomly selected transformants were analyzed by DNA sequencing, and most of the clones were found to have correct sequences. However, no correct construct was found from randomly selected transformants after traditional blunt-ended DNA ligation and transformation.