Use of Extracorporeal Physical Vibration Lithecbole Through Greater Sciatic Foramen for Treatment of Distal Ureteral Calculi.

Introduction: To evaluate the efficacy and safety of performing extracorporeal physical vibrational lithecbole (EPVL) through greater sciatic foramen (GSF) for distal ureteral calculi (DUC) treatment. Materials and Methods: All patients with a diagnosis of DUC (6-10 mm in diameter) were enrolled in this study from October 2018 to May 2020. Patients were randomly divided into three groups receiving EPVL through GSF (Group A, n = 58), or abdominal (Group B, n = 60), or combined with oral use of tamsulosin at 0.4 mg daily (Group C, n = 63). Results: There was no significant difference observed in terms of demographic characteristics or size of stones among the three groups (p > 0.05). Compared with the Groups B and C, patients of the Group A displayed a significantly higher score of comfort, with a significantly decreased number of renal colic attacks or analgesics required (p < 0.01). The stone-free rate also significantly increased after 1 and 2 weeks of treatment (p < 0.01), despite such a significant difference among these groups vanishing after 4 weeks of treatment. Conclusion: EPVL in the prone position uses the GSF as the path and is a safe and effective approach to treat the distal ureteral calculi.

Prediction of Proximal Ureteral Stones Clearance after Shock Wave Lithotripsy Using an Artificial Neural Network.

PURPOSE: The cumulative effect of measurable parameters on proximal ureteral stone clearance followed by the shock wave lithotripsy was assessed via the application of an artificial neural network. METHODS AND PATIENTS: From January 2015 to January 2020, 1182 patients with upper ureteral stone underwent extracorporeal shock wave lithotripsy (ESWL) with supine position. The corresponding significance of each variable inputted in this network was determined by means of Wilk's generalized likelihood ratio test. If the connection weight of a given variable can be set to zero while maximizing the accuracy of the network classification, the variable is not considered an important predictor of stone removal. RESULTS: A total of 1174 cases (excluding 8 cases) were randomly assigned into a training group (813 cases), testing group (270 cases), and keeping group (91 cases). We evaluated artificial neural network analysis to the stone clearance rate of the training group, with a predictive accuracy of 93.2% (482/517 cases). While the predictive accuracy of the stone clearance rate of the training group was 75.3% (223 cases/296 cases). The order of importance of independent variables was stone length > course (d) > patient's age > Stone Width > PH value. CONCLUSION: The neural network possess a huge prediction potential for the invalidation of ESWL.

External physical vibration lithecbole facilitating the expulsion of upper ureteric stones 1.0-2.0 cm after extracorporeal shock wave lithotripsy: a prospective randomized trial.

To observe the efficacy and safety of External Physical Vibration Lithecbole (EPVL) in patients with upper ureteric stones 1.0-2.0 cm after extracorporeal shock wave lithotripsy (ESWL). A total of 271 patients with upper ureteric stones 1.0-2.0 cm were prospectively randomized into two groups. One hundred and twenty-seven cases in the treatment group accepted EPVL therapy and 144 cases as control after ESWL. The stone expulsion status and stone-free rates (SFRs) between two groups were compared at the 1st, 2nd and 4th weekends by imaging examinations. All of 271 patients were randomly assigned to two groups, of which 127 patients were included in the treatment group and 144 in the control group. EPVL was successful in assisting the discharge of stone fragments. The rate of stone expulsion at day 1 in the treatment group was significantly higher than in the control group (79.5% vs. 64.6%, P = 0.006). The SFRs of the 1st weekend (76.3% vs. 61.8%, P = 0.010), the 2nd weekend (88.2% vs. 77.1%, P = 0.017) and the 4th weekend (92.1% vs. 84.0%, P = 0.042) in the treatment group were all significantly higher than that in the control group. However, no statistical significance was found in complications between the two groups (P > 0.05). Furthermore, in the treatment group the patients were treated a mean 4.3 sessions of EPVL. EPVL and ESWL are ideal complementary partners in the treatment of upper ureteric stones 1.0-2.0 cm, satisfying both high SFR and low complication. This method is safe and reproducible in clinical practice, and it also needs large-scale multicenter prospective studies further to prove the above conclusions.

Highly sensitive enumeration of circulating tumor cells in lung cancer patients using a size-based filtration microfluidic chip.

Circulating tumor cells (CTCs) in the peripheral blood could serve as a surrogate marker for the diagnosis of cancer metastasis and for therapeutic evaluation. However, the separation and characterization of CTCs is technically challenging owing to the extremely low number of CTCs present. Here we developed a size-based and high-throughput microfluidic chip, which exploits filtration microchannels to isolate the relatively larger CTCs from the rest of the blood constituents. High isolation efficiency of our microfluidic chip was demonstrated with three lung cancer cell lines spiked in blood samples at an optimal flow rate of 0.4 mL/h. The average recovery rates of 96%, 95% and 92% were obtained for A549, SK-MES-1, and H446, respectively. To clinically validate the chip, we also employed it to isolate CTCs from 59 lung cancer patients. CTCs were detected in 96.7% of patients with the mean number of 18.6 cells/mL, which was significantly higher than normal controls (P<0.05). The work here indicates that the size-based microfluidic platform with the advantage of capturing tumor cells without reliance on cell surface expression markers can provide a novel, inexpensive and effective tool for CTC detection and evaluation of cancer status.

Procyanidins inhibit tumor angiogenesis by crosslinking extracellular matrix.

OBJECTIVE: Procyanidins (PC) are widely available natural polyphenols. The present study is designed to investigate if PC can inhibit angiogenesis in lung adenocarcinoma xenografts through crosslinking vascular extracellular matrix (ECM) and preventing proteolysis by matrix metalloproteinases (MMPs). METHODS: Using the in vitro MMP-2 proteolysis and in vivo subcutaneous implantation models, we investigated if PC crosslinking inhibits MMP-mediated proteolysis. Using a cultured cell detachment assay, an in vitro angiogenesis assay, and a cell proliferation assay, we investigated if PC inhibits MMP-2-mediated endothelial cell detachment, angiogenesis, and cell proliferation, respectively. Using tumor xenografts, we evaluated if PC can inhibit growth of lung adenocarcinoma. RESULTS: PC crosslink vascular ECM proteins, protecting them against proteolysis by MMPs in vitro and in vivo, protecting cultured human umbilical vein endothelial cells from detachment by MMP-2, and inhibiting in vitro angiogenesis. However, PC (0.75-100 µg/ml) did not inhibit vascular and tumor cells proliferation. PC injections (30 mg PC/kg bodyweight) in situ had anticancer effects on xenografts of lung adenocarcinoma, most likely by inhibiting angiogenesis during ECM proteolysis by MMPs. CONCLUSION: The results suggest that PC may be important MMP inhibitors that can be used as therapeutic anticancer agents.

Nano-ELISA for highly sensitive protein detection.

Highly sensitive protein detection method based on nanoparticles and enzyme-linked immunosorbent assays (ELISAs), named Nano-ELISA, was introduced. In this method, the micro-magnetic beads were modified with monoclonal antibody of the target protein p53. Gold nanoparticles (AuNPs) were modified with another monoclonal detector antibody and Horseradish peroxidase (HRP, for signal amplification). The presence of target protein p53 causes the formation of the sandwich structures (magnetic beads-target protein-AuNP probes) through the interaction between the antibodies and the antigen p53. The HRP at the surface of AuNPs catalytically oxidize the substrate and generate optical signals that reflected the quantity of the target protein. Down to 5 pg mL(-1) of protein was detected in less than 2 h with this method. The detection sensitivity of p53 classic ELISA kit is 0.125 ng mL(-1). This method is as simple as ELISA and has higher sensitivity than ELISA, which can potentially be exploited in clinic. This method can be used to detect protein markers of tumors, nervous system or other diseases for early diagnostics.

Microchip-based capillary electrophoresis for determination of lactate dehydrogenase isoenzymes.

This article describes a novel microchip-based capillary electrophoresis and oncolumn enzymatic reaction analysis protocol for lactate dehydrogenase (LDH) isoenzymes with a home-made xenon lamp-induced fluorescence detection system. A microchip integrated with a temperature-control unit is designed and fabricated for low-temperature electrophoretic separation of LDH isoenzymes, optimal enzyme reaction temperature control, and product detection. A four-step operation and temperature control are employed for the determination of LDH activity by on-chip monitoring of the amount of incubation product of NADH during the fixed incubation period and at a fixed temperature. Experiments on the determination of LDH standard sample and serum LDH isoenzymes from a healthy adult donor are carried out. The results are comparable with those obtained by conventional CE. Shorter analysis times and a more stable and lower background baseline can be achieved. The efficient separation of different LDH forms indicates the potential of microfluidic devices for isoenzyme assay.

Effects of human locus control region elements HS2 and HS3 on human beta-globin gene expression in transgenic mouse.

The locus control region (LCR) is the most important cis-element in the regulation of beta-globin gene expression. DNaseI-hypersensitive site (HS) 2 and HS3 are two significant components of beta-LCR. To examine the effect of HS2, HS3, and HS2-HS3 (combination of HS2 and HS3) on the spatial and temporal expression of the human beta-globin gene, we have produced transgenic mice with constructs, in which the gene encoding enhanced green fluorescent protein (EGFP) is driven by beta-globin promoter and under the control of HS2, HS3, and HS2-HS3, respectively. The results showed that HS2 and HS3 each had the same enhancement activity in regulation of beta-globin gene expression in transgenic mice. When HS2 and HS3 were in combination (HS2-HS3), the two cis-elements showed a marked synergy in regulating beta-globin gene spatial and temporal expression as well as its expression level in transgenic mice although the EGFP expression varied largely among different transgenic mouse litters. The results also showed that HS2 was able to confer beta-globin gene expression in embryonic yolk sac, fetal liver, and adult bone marrow, which was not developmentally stage-specific, while HS3 could confer the same beta-globin gene expression in the adult. Thus, HS3 was different from HS2, the former being more important for specific expression of beta-globin gene in the developmental stages and the switch of gamma-->beta-globin genes. Our results indicate that the mechanism of gamma-->beta switch could be best explained by the "divided model."

[A study of the effect of locus control region elements HS2 and HS3 on beta-globin gene expression].

HS2 and HS3 are important elements of human beta-globin locus control region (LCR). To study the effect of HS2, HS3, and HS2-HS3 on human beta-globin gene expression, a series of expression cassettes were constructed, in which the reporter gene encoding the enhanced green fluorescent protein (EGFP) was driven by the beta-globin promotor and under the control of HS2, HS3, and HS2-HS3. These constructs were transfected transiently into MEL and K562 cell lines mediated with liposome and their expression was measured with FACS as well as semi-quantitative RT-PCR method. The results showed that 3.2-kb HS2 could significantly enhance the activity of beta-globin promotor in MEL and K562 cells, while 3-kb HS3 could do only in MEL cells. There was no synergistic function in transient expression in the cassettes with the combination of HS2 and HS3 in MEL and K562 cells.

[A study of inductive effect of hemin on expression of the beta-globin genes in K562 cells].

The recombinant plasmid HG was constructed,in which the reporter gene encoding the enhanced green fluorescent protein (EGFP) was driven by the beta-globin promoter and regulated under the HS2 element. The inductive effect of hemin on the expression of the beta-globin gene and transiently transfected beta-globin genes in K562 cells was analysed by FACS as well as RT-PCR method. The results showed that the level of gamma and beta-globin gene mRNA in K562 cells increased significantly after 24,48 and 72 hours induced with 30 micromol/LHm.And this inductive effect was stronger after 24 and 48 hours. Furthermore,the transient expression of plasmid HG in K562 cells increased significantly with hemin induction. These results indicated that the mechanism of inductive erythroid differentiation with hemin may be correlated with mechanism of gamma-->beta-globin gene.