A novel strategy for the quality control of carbonized Typhae pollen using colorimeter, liquid chromatography-mass spectrometry, and efficacy evaluation coupled with multivariate statistical analysis.

In this study, a novel quality control strategy was proposed, aiming to establish a multivariate specification for the processing step by exploring the correlation between colors, chemical components, and hemostatic effects of the carbonized Typhae pollen (CTP) using multivariate statistical analysis. The CTP samples were stir-fried at different durations. Afterward, the colorimeter and LC-MS techniques were applied to characterize the CTP samples, followed by the determination of bleeding time and clotting time using mice to evaluate their hemostatic effect. Then, principal component analysis, hierarchical cluster analysis, and multi-block partial least squares were used for data analysis on colors, chemical components, and their correlation with the hemostatic effect. Consequently, 13 critical quality attributes (CQAs) of CTP were identified via multivariate statistical analysis-L*, a*, b*, 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, 3-hydroxybenzoic acid, quercetin-3-O-glucoside, azelaic acid, kaempferol-3-O-glucoside, quercetin, naringenin, kaempferol, and isorhamnetin. The multivariate specification method involving the 13 CQAs was developed and visualized in the latent variable space of the partial least squares model, indicating that the proposed method was successfully applied to assess the quality of CTP and the degree of carbonization. Most importantly, this study offers a novel insight into the control of processing for carbonized Chinese herbal medicines.

Downregulation of clusterin expression in human testicular seminoma.

BACKGROUND: Clusterin, a heterodimeric glycoprotein of approximately 80 kDa, exists extensively in human body fluids. The abnormal expression of clusterin is closely related to the occurrence, progression, and prognosis of tumors. Up to now, few studies have focused on clusterin in human testicular cancer. This study describes an extensive exploration of the presence and expression of clusterin in testicular seminoma. METHODS: Tumor tissues and normal testis tissues were collected from 13 patients with testicular seminoma and 16 patients undergoing surgical castration for prostate cancer. Real-time polymerase chain reaction (PCR) was performed to detect the expression difference of clusterin mRNA between testicular seminoma and normal testis. Western blot and immunohistochemical analysis were performed to detect the presence and expression difference of clusterin protein between two groups. RESULTS: Real-time PCR showed the expression of clusterin mRNA in testicular seminoma to be significantly lower than in normal testis (only 13% relative quantification). Western blot analysis indicated marked reductions in the expression of clusterin protein in testicular seminoma. Similar results were observed upon immunohistochemical analysis. CONCLUSION: In testicular seminoma and normal testis, clusterin exists in its heterodimeric secretory isoform. Clusterin expression is significantly lower in testicular seminoma than in normal testis. This is the first comprehensive study of the presence and expression of clusterin in human testicular cancer.

Intracardiac echocardiography Chinese expert consensus.

In recent years, percutaneous catheter interventions have continuously evolved, becoming an essential strategy for interventional diagnosis and treatment of many structural heart diseases and arrhythmias. Along with the increasing complexity of cardiac interventions comes ever more complex demands for intraoperative imaging. Intracardiac echocardiography (ICE) is well-suited for these requirements with real-time imaging, real-time monitoring for intraoperative complications, and a well-tolerated procedure. As a result, ICE is increasingly used many types of cardiac interventions. Given the lack of relevant guidelines at home and abroad and to promote and standardize the clinical applications of ICE, the members of this panel extensively evaluated relevant research findings, and they developed this consensus document after discussions and correlation with front-line clinical work experience, aiming to provide guidance for clinicians and to further improve interventional cardiovascular diagnosis and treatment procedures.

Correlation Between Pulmonary Sclerosing Pneumocytoma Features and MSCT Imaging Manifestations in 34 Patients: Implications for Precision Medicine.

Objective: To identify and analyze the multi-slice computed tomography (MSCT) imaging manifestations and clinicopathological features of PSP to improve the preoperative and intraoperative diagnosis of the disease. Method: This was a retrospective study conducted on the imaging and clinicopathological data of the PSP patients treated in two major hospitals in China from October 2001 to December 2019. The locations of lung lesions, clinical symptoms, surgical complications, MSCT imaging features, and the corresponding relationship with clinicopathological features were assessed. Then, a new diagnostic approach was defined and used to train imaging and pathological doctors (experimental group). Then, the diagnostic accuracy of the experimental group was evaluated in preoperative and intraoperative diagnosis of PSP. Results: Thirty-four PSP cases were analyzed (mean: 51.42; range: 39-69 years old). The peripheral type was more common, while 92% of the lesions located in the middle lobe of the right lung and the lower lobe of bilateral lungs. The shortest lesion edge-pleura distance ranged 0 to 30 mm and 46% of the lesions (16/34) were attached to the pleura, 62% (21/34) located at 0-5 mm, 92% (31/34) within 20 mm from the pleura. Diameters of the lesions ranged 8.58 to 68.41 mm, while most of them were 20-40 mm. All lesions showed enhancement, and 97% (33/34) were unevenly enhanced. PSP volume was negatively correlated with the total degree of enhancement (r = -0.587, p < 0.01), and the volume difference between the obvious enhancement zone and the slight enhancement zone (r = -0.795, p < 0.01). Welt vessel sign was observed in 61.7% (21/34) of cases, and none of welt vessels entered into the lesions. Vascular-like enhancement area inside the lesion showed no significant correlation with the welt vessels outside the lesion, and no case showed entrance of bronchus into the lesion. The trained experimental group showed significantly greater diagnostic accuracy than the control group. In particular, the accuracy rate of intraoperative frozen section diagnosis was 60% higher in the experimental group than the control group. Conclusion: PSP has characteristic imaging manifestations, which can be utilized to improve the preoperative and intraoperative diagnostic coincidence rate of PSP.

Ectopic atrial tachycardias with early activation at His site: radiofrequency ablation through a retrograde approach.

AIMS: The purpose of this study was to evaluate a retrograde approach for radiofrequency (RF) ablation of ectopic atrial tachycardias (EATs) with an early atrial activation at the His site. METHODS AND RESULTS: This study included 12 patients with EAT. During tachycardia, earliest atrial activation was recorded at the His site at a standard catheter setting. Activation mapping was performed in the right atrium and along the mitral annulus and at the aortic root after retrograde insertion of the ablation catheter over the ascending aorta. In five patients, earliest atrial activation was recorded at the mitral annulus (in two patients at the superior-lateral annulus and in three patients at the inferior-medial annulus). In four of these patients, EAT could be successfully treated by RF ablation through the retrograde approach, whereas in one patient, a transseptal puncture was performed in order to achieve a stable catheter position. In seven patients, RF ablation at the non-coronary aortic sinus eliminated the tachycardia. During a follow-up period of 14 +/- 8 months, there was no tachycardia recurrence. CONCLUSION: In patients with EATs and early atrial activation at the His site, tachycardia may arise in the non-coronary aortic sinus or from the mitral annulus. Radiofrequency energy ablation can be performed through a retrograde approach in the majority of these patients and is safe and effective in eliminating this type of tachycardia.

Alterations of a spectrum of driver genes in female Chinese patients with advanced or metastatic squamous cell carcinoma of the lung.

OBJECTIVES: Female patients with squamous cell carcinomas of the lung (SQCLC) in China differ from male patients in that most females are life-long never/light smokers. We hypothesized that the clinical characteristics and mutation profiles of a spectrum of driver genes in Chinese female patients with advanced SQCLC would also differ from those of male patients. PATIENTS AND METHODS: We examined the pathological subtype of SQCLC retrospectively by immunohistochemistry (IHC) and screened 38 female and 40 male patients with IIIB/IV-stage SQCLC in China from 2009 to 2012. Mutation analyses of EGFR, PIK3CA, KRAS, and PTEN were performed using PCR-based DNA sequencing. FGFR1 amplification and ALK rearrangements were detected by fluorescent in situ hybridization (FISH). A Cox regression model was used to assess the association between clinical features and genomic mutation status. RESULTS: There were significantly fewer female patients with a history of smoking than males (5.3% vs. 90%; P<0.001). A younger average age at diagnosis (54.5 vs. 61 years; P=0.032) and a higher percentage of peripheral-type disease (47.4% vs. 25.0%; P=0.040) were observed in females. No difference in ECOG score, tumor size, metastatic status, or overall survival between females and males was seen. PIK3CA mutations were significantly less common in female patients than males (0/38 vs. 6/40; P=0.026). However, no significant difference in the mutational frequencies of EGFR, KRAS, PTEN, ALK, or FGFR1 was observed between females and males. CONCLUSIONS: Our data demonstrated that female patients with SQCLC are apparently a subtype, with a significantly lower percentage having a smoking history, a younger average age at diagnosis, a higher percentage of peripheral-type disease on radiological presentation, and a lower frequency of PIK3CA mutations. Given the similar survival outcomes between the genders, whether it is a distinct disease entity needs to be studied further in larger populations.

Interference effect of epigallocatechin-3-gallate on targets of nuclear factor kappaB signal transduction pathways activated by EB virus encoded latent membrane protein 1.

AIM: To elucidate the interference effect of epigallocatechin-3-gallate (EGCG) on targets of nuclear factor kappaB (NF-kappaB) signal transduction pathway activated by EB virus encoded latent membrane protein 1 (LMP1) in nasopharyngeal carcinoma (NPC) cell lines. METHODS: The survival rates of CNE1 and CNE-LMP1 cell lines after the EGCG treatment were determined by MTT assay. NF-kappaB activation in CNE1 and CNE-LMP1 cells after EGCG treatment was analyzed by promoter luciferase reporter system. And then nuclear translocation of NF-kappaB (p65) after the EGCG treatment was analyzed by immunofluorescence and western blotting. Meanwhile, the changes of IkappaBalpha phosphorylation were observed after the EGCG treatment. EGFR promoter activity was analyzed by promoter luciferase reporter system and EGFR phosphorylation was observed by western blotting after the EGCG treatment. RESULTS: EGCG inhibited the survival rates of CNE1 and CNE-LMP1 cells and NF-kappaB activation caused by LMP1 in CNE-LMP1 cells. EGCG also suppressed the nuclear translocation of NF-kappaB (p65) and IkappaBalpha phosphorylation. Meanwhile, EGCG inhibited EGFR promoter activity and EGFR phosphorylation. CONCLUSIONS: EGCG inhibited not only the dose-dependent survival rate of NPC cells, but also the dose-dependent activation of NF-kappaB. This inhibition of LMP1-caused NF-kappaB activation was mediated via the phosphorylative degradation of its inhibitory protein IkappaBalpha, and then EGCG inhibited EGFR activity which was a downstream gene from NF-kappaB. This study suggests that interference effect of EGCG on targets of signal transduction pathway plays an important role in the anticancer function.

The effect of placebo adherence on reducing cardiovascular mortality: a meta-analysis.

OBJECTIVE: We aim to demonstrate the effect of placebo adherence on reducing CV mortality. BACKGROUNDS: Good adherence, whether to drug or placebo treatment, is associated with lower CV mortality. However, current evidence for the positive effect of placebo adherence on reducing CV mortality is relatively weak. METHODS: We conducted a fixed-effect meta-analysis of eight randomized clinical trials to evaluate the effect of placebo adherence on reducing CV mortality. We made a comparison between good placebo adherence and poor drug adherence. RESULTS: Compared with poor adherence to drug treatment, good adherence to placebo treatment was associated with lower CV mortality (OR = 0.68, 95% CI 0.60-0.77). CONCLUSION: Good adherence to placebo has a positive effect on reducing CV mortality. The effect of adherence on reducing CV mortality may be independent of the drug effect.

New evidences for fractalkine/CX3CL1 involved in substantia nigral microglial activation and behavioral changes in a rat model of Parkinson's disease.

Activated microglia are instrumental to neurodegeneration in Parkinson's disease (PD). Fractalkine, as an exclusive ligand for CX3CR1 expressed on microglia, has recently been reported to be released out by neurons, and induce microglial activation as a neuron-to-glia signal in the spinal cord. However, the role of fractalkine-induced microglial activation in PD remains unknown. In our study, we injected 1-methyl-4-phenylpyridinium (MPP(+)) into unilateral substantia nigra (SN) which induced ipsilateral endogenous fractalkine expression on neuron and observe the increase of CX3CR1 expression in response to MPP(+) by Western blotting analysis. Moreover, pre-administration of anti-CX3CR1 neutralizing antibody which potentially blocked microglial activation can promote rotation behaviors. To further investigate the role of fractalkine in PD, we injected exogenous fractalkine in unilateral SN, and observed microglial activation, dopaminergic cell depletion, and motor dysfunction. All these effects can be totally abolished by cerebroventricular administration of anti-CX3CR1. Intracerebroventricular administration of minocycline, a selective microglia inhibitor, can prevent fractalkine-induced rotation behaviors, and inhibit dopaminergic neurons from degeneration in the way of dose-dependent. Our studies demonstrate that fractalkine-induced microglial activation plays an important role in the development of PD, and provide an evidence of fractalkine and CX3CR1 as new therapeutic targets for PD treatment.

HSV-tk/GCV gene therapy mediated by EBV-LMP1 for EBV-associated cancer.

BACKGROUND: To investigate the feasibility of gene therapy in treating Epstein-Barr virus (EBV)-associated cancer by employing the suicide gene, herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV), which uses the signaling pathway through the HIV-long terminal repeat (LTR) gene which is expressed from a nuclear factor-kappaB (NF-kappaB)-binding motif-containing promoter that is regulated by EBV-latent membrane protein 1 (LMP1) via NF-kappaB. METHODS: First, we constructed the plasmid pVLTR-tk, which was regulated by EBV-LMP1 via NF-kappaB, and then investigated the cytotoxic effect of the pVLTR-tk/GCV on cancer cells, using MTT assays, clonogenic assays, flow cytometry, and animal experiments. RESULTS: The activation of TK was increased after transfection of the pVLTR-tk into the EBV-LMP1 positive cells. After GCV treatment, the clonogenicity and survival of the cells substantially declined, and a bystander effect was also observed. The LMP1 positive cells exhibited remarkable apoptosis following pVLTR-tk/GCV treatment, and the pVLTR-tk/GCV restrained tumor growth in vivo for EBV-LMP1 positive cancers. CONCLUSION: The pVLTR-tk/GCV suicide gene system may be used as a new gene targeting strategy for EBV-associated cancer.

Study and implementation of a novel ultrasound imaging technique combining digital beamforming with synthetical aperture.

Aiming at higher performances and lower cost of an ultrasonic imaging system, a novel digital imaging approach was proposed, which combines the dual beamforming technique to double frame rate with the synthetical aperture technique to halve receive channels. Besides theoretical analyses and simulations, its hardware implementation was discussed in detail, embodied and finally tested on a real ultrasonic imaging system. The experimental results show that with this approach, system cost can be remarkably reduced without lowering the frame rate and image quality.

Detection of Impedance Cardioaraphy's Characteristic Points Based on Wavelet Transform.

With observation that singularities of a multi-scale wavelet transform result are related to discontinuities of the signal, a novel wavelet transform based method is proposed in this paper for detection of biomedical signals' characteristic points. For impedance cardiography signals, characteristic points of the signal dz/dt, including its peaks, start-point and end-point of ventricular ejection are detected and located by using singularities of wavelet transform (e.g., crossover points, maxima, minima). Experiment results showed validity of the approach.

Epstein-Barr virus LMP1 initiates cell proliferation and apoptosis inhibition via regulating expression of Survivin in nasopharyngeal carcinoma.

UNLABELLED: Pathways controling cell proliferation and cell survival require flexible adaptation to environmental stress. Our previous studies showed that latent membrane protein1 (LMP1) encoded by Epstein-Barr virus (EBV) could trigger the expression of Survivin, an apoptosis inhibitor and essential regulator of mitosis. The aim of the work was to analyze the role of Survivin signal pathway in mediating effects triggered by LMP1. METHODS: Tet-on LMP1 HNE2, a tetracycline-regulated LMP1-expression nasopharyngeal carcinoma cell line, was used as cell model. The subcellular location of Survivin was detected by indirect immunofluorescence and Western-blotting assay. Using Ab-knock-out and gene transfection, we introduced anti-sense PS-ODN-Survivin and anti-body to Survivin into the Tet-on LMP1 HNE2, and then the apoptosis and the proliferation of cells were analyzed by flow cytometry, cell colony formation and detection of caspase-3. The results show that upon induction of LMP1 expression, the expression of Survivin in nucleus, level of phosphorylated retinoblastoma gene (Rb), the number of cells in S stage of cell cycle, and the cell colony formation rate were higher than those without LMP1 induction; if the expression of Survivin and the nucleus translocation of Survivin were knocked by introduction of anti-sense PS-ODN-Survivin and anti-Survivin-antibodies respectively, apoptosis rates and the activity of caspase-3 increased. CONCLUSION: LMP1 could trigger the nucleus translocation of Survivin, which led to the shift of S stage and cell proliferation. LMP1 may promote cell proliferation and inhibits apoptosis via Survivin signal pathway.