Tumor immunotherapy has been a research hotspot in the field of tumor therapy in recent years,especially the successful development and application of immune checkpoint inhibitors,which has brought tumor immunotherapy into a new era.Unlike conventional treatment methods,such as chemotherapy,radiotherapy,and targeted therapy which directly affect tumor cells,immune checkpoint inhibitors block tumor immune environment checkpoint pathways and stimulate tumor-specific T cell functions to achieve anti-tumor effects.However,the clinical efficacy evaluation of immune checkpoint blockers still faces many challenges,and the solid tumor evaluation criteria(response evaluation criteria in solid tumors,RECIST)applicable to traditional chemotherapy drugs cannot accurately assess the efficacy of immunotherapy.Immune-related response criteria need further research.

Labor pain is a kind of severe pain the lying-in women of natural childbirth must undergo. The labor quality is decided by the tolerance to pain. Acupuncture analgesia for labor pain has been increasingly concerned and applied by more and more clinical workers because of its safety and efficacy. By summarizing and analyzing the choice and applications of various factors of acupuncture analgesia for labor pain such as acupoint selection, instrument analgesic coefficient, and the needling techniques in acupuncture analgesia for labor pain in the recent 12 years, this study aims to provide a theoretical foundation for the clinical application of acupuncture analgesia for labor pain.

Abstract Capillary electrophoresis based systematic evolution of ligands via exponential enrichment (CE-SELEX) was reported as a homogeneous efficient method for high-affinity selection of aptamer, with several merits involving screening in free solution without nonspecific binding, capable of high-efficient separation, low-sample consumption, and saving money. There are few studies regarding the aptamer selection against small molecule using CE-SELEX, resulting from the aspects of less binding sites and the negligible variety of its complex with nucleic acid in the electrophoretic mobility. In this study, we performed the aptamer selection towards a small molecule target of clenbuterol hydrochloride (Clen) by CE-SELEX. In brief, Clen were first incubated with an 80 nt ssDNA library, and CZE-UV approach was used to separate complex and random ssDNA. The complex was then collected into a vial followed by PCR amplification. Through three round selections, the third library was selected to clone and ten sequences were finally obtained. The dissociation constant ( K d ) of three potential candidates (Apt 4, Apt 7 and Apt 12) were determined by CE-LIF, and showed high affinities of 9.315 × 10 −7 M, 1.040 × 10 −6 M and 1.143 × 10 −5 M, respectively. The result of m-Fold software analysis showed that the above three sequences could form stem-loop structure, and the Apt 4 gave the lowest free energy and the most stable structure. Using salbutamol as a control, three selected aptamers were verified with high specificity. Graphical abstract Clen were first incubated with an 80 nt ssDNA library, and CZE-UV approach was used to separate complex and random ssDNA. The complex was then collected into a vial followed by PCR amplification. Through three round selections, the third library was selected to clone and ten sequences were finally obtained. Aptamer affinity and specificity were analyzed and compared by AuNPs colorimetry, GO-capillary electrophoresis. Using salbutamol as a control, three selected aptamers were verified with high affinity and specificity.

Based on the principle of virtual work, an updated Lagrangian finite element formulation for the geometrical large deformation analysis of galloping of the iced conductor in an overhead transmission line is developed. In numerical simulation, a threenode isoparametric cable element with three translational and one torsional degrees-offreedom at each node is used to discretize the transmission line. The nonlinear dynamic system equation is solved with the Newmark time integration method and the Newton-Raphson nonlinear iteration. Numerical examples demonstrate the efficiency of the presented method and the developed finite element program. A new possible galloping mode, which may reflect the saturation phenomenon of a nonlinear dynamic system, is discovered under the condition that the lowest order of vertical natural frequency of the transmission line is approximately two times of the horizontal one.

This paper presents a new test to distinguish between meaningful and non-meaningful HMM-modeled activity patterns in human activity recognition systems. Operating as a hypothesis test, alternative models are generated from available classes and the decision is based on a likelihood ratio test (LRT). The proposed test differs from traditional LRTs in two aspects. Firstly, the likelihood ratio, which is called pairwise likelihood ratio (PLR), is based on each pair of HMMs. Models for non-meaningful patterns are not required. Secondly, the distribution of the likelihood ratios, rather than a fixed threshold, is used as the measurement. Multiple measurements from multiple PLR tests are combined to improve the rejection accuracy. The advantage of the proposed test is that the establishment of such a test relies only on the meaningful samples. [All rights reserved Elsevier].

Objective In order to observe the therapeutic effect of Eight Battle Points for simple obesity.

Abstract The interaction of gatifloxacin (HGA) with bovine serum albumin (BSA) at 15 and 37 °C has been investigated by fluorescence quenching spectroscopy in aqueous solution. The bimolecular quenching rate constant was determined by Stern-Volmer curves and the values were Kq=9.28×1012 L·mol−1·s−1 (15 °C) and Kq=8.51×1012 L·mol−1·s−1 (37 °C). The results showed that the fluorescence quenching mechanism of BSA by HGA was a static quenching procedure. The thermodynamic parameters indicated that electrostatic forces played major role in the interaction of BSA with HGA. Studies on the relationship between the concentration of HGA and the fluorescence intensity of BSA >showed that BSA and HGA bound at the molar ratio 1:1 and the equilibrium constant K0 was 6.80×104 L·mol−1. The binding distances between BSA and HGA and the energy transfer efficiency were obtained based on the FÖrster's theory.

Objective:Several studies indicated that many factors have relationship with the metastatic sites of advanced breast cancer.This retrospective study investigated the high risk factors which related to the different metastatic sites of stage IV breast cancer.Patients and methods:From January 2003 to December 2005 a total of 387 consecutive breast cancer patients were retrospectively analyzed.The relationships between different categorical variables and breast cancer were identified by Chi-square tests.Results:The high risk factors of metastatic breast cancer included the overexpression of HER-2 and lymph nodes invasion.The overexpression of HER-2 and lymph nodes invasion had a significantly difference between metastatic breast cancer and breast cancer without metastasis(P=0.018,P<0.001,respectively).As for metastatic breast cancer patients with only one single metastatic organ,the overexpression of HER-2 had a significantly high positive rate in patients with visceral metastases when compared with bone metastasis(P=0.045).Conclusion:The overexpression of HER-2 and lymph nodes invasion significantly influenced the metastasis of breast cancer.Overexpression of Her-2 was high risk factors for breast cancer developed to visceral metastases disease.

Objectives. Hua-Zheng-Hui-Sheng-Dan (HZHSD) was used as an experimental model to explore research methods of large formulae in traditional Chinese medicine (TCM) using current molecular biology approaches. Materials and Methods. The trypan blue exclusion assay was used to determine cell viability and cell numbers. Flow cytometry was used to assess cell cycle distribution and apoptosis. The concentration of cyclin D1 was analyzed by enzyme-linked immunosorbent assay. The median effect principle was used in drug combination studies. An orthogonal experimental design was used to estimate the effects of each herb at different concentrations. The HeLa xenograft mouse model was used to compare the antitumor activity of drugs in vivo. Results. Among the 35 herbs that comprise HZHSD, Radix Rehmanniae Preparata (RRP), Caesalpinia sappan (CS), Evodia rutaecarpa (ER), Folium Artemisiae Argyi (FAA), Leonurus japonicus Houtt (LJH), Tumeric (Tu), Radix Paeoniae Alba (RPA), and Trogopterus Dung (TD) effectively inhibited the proliferation of HeLa and SKOV3 cells. Only RRR had an effect on HeLa and SKOV3 cell viability. According to the median effect principle, Angelica sinensis (Oliv.) (AS), Tabanus (Ta), and Pollen Typhae (PT), which were proven to have a significant synergistic inhibitory effect on the proliferation of HeLa cells, were added to the original eight positive herbs. The combination of RPA and AS had a synergistic effect on inducing cell cycle S phase arrest and decreasing intracellular cyclin D1 in HeLa cells. By orthogonal experimental design, LJH and Tu were considered unnecessary herbs. The small formula (SHZHSD) consisted of RPA, AS, RRR, Ta., TD, PT, ER, CS, and FAA and was able to inhibit cell proliferation and induce cell apoptosis. The antitumor effects of HZHSD and SHZHSD were also compared in vivo. Conclusions. Through molecular biology approaches both in vitro and in vivo, research into single drugs, and analysis using the median effect principle and orthogonal experimental design, the small formula (SHZHSD) was determined from the original formula (HZHSD). SHZHSD exhibited superior antitumor activity compared with the original formula both in vitro and in vivo.

Binary solid solutions 0.7BiFeO 3-0.3BaTiO 3-xwt.% MnO2 (x=0, 0.2, 0.3, and 0.5) were prepared by a traditional ceramic process. All ceramic samples show single perovskite phase. The effect of manganese doping on structure, dielectric, ferroelectric and ferromagnetic properties, and resistivity was investigated. Results show that Mn-dopant can improve the sintering ability of the materials when MnO 2 content is below 0.3 wt.%. When MnO 2 content exceeds 0.3 wt.%, the sintering ability is weakened and the phase structure of 0.7BiFeO 3-0.3BaTiO 3 solid solution changes from rhombohedral into tetragonal phase. With increasing concentration of MnO 2, the resistivity increases at first and then decreases. Whereas the coercive electric field decreases at first and then increases, the remanent magnetization Mr increases and the coercive magnetic field decreases. [All rights reserved Elsevier].

0.7Bi(Fe 1-xCr x)O 3-0.1BaTiO 3-0.2PbTiO 3 (x = 0, 0.1, 0.2, 0.3) solid solutions were prepared by the traditional ceramic process. X-ray diffraction results revealed that the samples with x = 0-0.3 showed pure perovskite structure. Frequency and temperature dependences of dielectric constants and dielectric loss of the samples were investigated. Both dielectric constant and the loss tangent increased at given frequencies (100 Hz-1 MHz), while the Curie temperature of the solid solutions decreased with increasing Cr content. Room temperature magnetic hysteresis loops indicated that an appropriate amount of Cr could improve magnetization of the solid solutions. [All rights reserved Elsevier].

The interaction of 1-phenyl-3-(coumarin-6-yl)sulfonylurea (SU22) with bovine serum albumin (BSA) has been investigated by fluorescence quenching spectroscopy combined with UV-absorption, circular dichroism (CD), Fourier transform infrared (FT-IR) spectroscopy techniques under simulative physiological conditions for the first time. Fluorescence data and UV-absorption spectra revealed that the quenching mechanism of fluorescence of BSA by SU22 was a static quenching process and the number of binding sites was about 0.8858; the thermodynamic parameters (ΔG = −29.23 kJ mol−1, ΔH = −47.48 kJ mol−1, and ΔS = −61.24 J mol−1 K−1) explained that hydrogen bond and Van der Waals interaction were the main binding force stabilizing the complex. The binding average distance between SU22 and BSA was obtained (3.20 nm) on the basis of the Förster’s theory. In addition, The CD spectra and FT-IR spectra have proved that BSA secondary structure changed in the presence of SU22 in aqueous solution.

The interaction of 1-phenyl-3-(coumarin-6-yl)sulfonylurea (SU22) with bovine serum albumin (BSA) has been investigated by fluorescence quenching spectroscopy combined with UV-absorption, circular dichroism (CD), Fourier transform infrared (FT-IR) spectroscopy techniques under simulative physiological conditions for the first time. Fluorescence data and UV-absorption spectra revealed that the quenching mechanism of fluorescence of BSA by SU22 was a static quenching process and the number of binding sites was about 0.8858; the thermodynamic parameters (ΔG = −29.23 kJ mol−1, ΔH = −47.48 kJ mol−1, and ΔS = −61.24 J mol−1 K−1) explained that hydrogen bond and Van der Waals interaction were the main binding force stabilizing the complex. The binding average distance between SU22 and BSA was obtained (3.20 nm) on the basis of the Förster’s theory. In addition, The CD spectra and FT-IR spectra have proved that BSA secondary structure changed in the presence of SU22 in aqueous solution.

The present invention relates to pharmaceutical formulations comprising the protein kinase inhibitor, MP470, and methods of using same in treating conditions involving undesirable cell proliferation, such as cancer.