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An efficient method based on ultrafiltration high-performance liquid chromatography coupled with photodiode array detector and electrospray ionization mass spectrometry for the rapid screening and identified of the ligands for activated from the extract of Trifolium repens L. Five major compounds, namely ononin, daidzein, genistein, formononetin, and biochanin A, were identified as potentially effective inhibitors. Subsequently, the specific binding ligands were separated by stepwise flow rate high-speed countercurrent chromatography and semipreparative high-performance liquid chromatography. This is the first report that T. repens extracts contain potent lipoxidase inhibitors. In summary, we systematically studied the active components in T. repens, evaluated their activity, separated and purified them, and identified their structure. This method is simple, fast, and efficient. It is suitable for the separation and purification of active compounds in T. repens, and provides a theoretical basis and technical platform for the development of natural medicines.

Background and aim Endoscopic submucosal dissection (ESD) has a high en bloc resection rate and is widely performed for large colorectal lesions. However, colorectal ESD is associated with a high frequency of adverse events (AEs), and the efficacy of prophylactic endoscopic closure after ESD for preventing AEs is still controversial. This meta-analysis was conducted to assess the efficacy of closure on AEs following colorectal ESD. Methods We searched PubMed, Embase, and the Cochrane Library for eligible studies. The chi-square-based Q statistics and the I2 test were used to test for heterogeneity. Pooling was conducted using a fixed or random effects model. Results We identified eight eligible studies that compared the effects of closure vs non-closure with respect to delayed bleeding, delayed perforation, and post-ESD coagulation syndrome. Compared with non-closure (5.2%), closure was associated with a lower incidence (0.9%) of delayed bleeding (pooled odd ratios [ORs]:0.19, 95% CI: 0.08-0.49) following ESD. The pooled ORs showed no significant differences in incidence of delayed perforation (pooled OR: 0.22; 95% CI: 0.05-1.03) or post-ESD coagulation syndrome (pooled OR:0.75; 95% CI: 0.26-2.18) between the closure and non-closure groups. Conclusion Prophylactic endoscopic closure may reduce the incidence of delayed bleeding following ESD of colorectal lesions. Future studies are needed to further illuminate risk factors and stratify high risk subjects for a cost-effective preventive strategy.

The study aimed to assess whether caesarean section and nonbreastfeeding can prevent mother-to-child transmission (MTCT) in HBsAg- and HBeAg-positive mothers via a cohort study and a meta-analysis. (1) Pregnant women who were positive for HBsAg and HBeAg and did not receive antiviral treatment during pregnancy were recruited from the First Hospital of Jilin University, Maternal and Child Health Care Center of Jiangsu and Henan from August 2009 to June 2015. Infants received active and passive immunity. (2) In addition, a systematic literature search was performed in the PubMed, Embase, Cochrane, China National Knowledge Infrastructure and Wanfang Chinese databases. The retrieval strategy was [("HBV" or "hepatitis b" or "hepatitis b virus") and ("mother-to-infant transmission" or "vertical transmission")]. Studies were screened, and data were extracted. The fixed-effect model was used to analyse the studies. A total of 852 mothers and 857 newborns were enrolled. At the age of 7 months, 41 infants (4.78%) were positive for HBsAg. Multivariate analysis showed that mothers with higher HBV DNA levels (>108 IU/mL; RR = 3.03, 95% CI: 1.41-6.52) were associated with an increased risk of infection. Although there was no statistical significance, caesarean section (RR = 0.61) and nonbreastfeeding (RR = 0.88) showed a tendency to reduce the risk of infection. (2) A total of 5726 studies were identified. Together with our study, 13 were included in the analysis of delivery mode, and 12 were included in the analysis of feeding mode. The risk of infection in the caesarean section group was lower than that in the vaginal delivery group (RR = 0.58, 95% CI: 0.46-0.74). In the analysis of feeding mode, the risk in the nonbreastfeeding group was significantly lower (RR = 0.74, 95% CI: 0.56-0.98). In conclusion, caesarean section and nonbreastfeeding reduced the risk of MTCT in infants of HBsAg- and HBeAg-positive mothers who did not receive antiviral therapy during pregnancy.

Background The distant metastasis (DM) mode and treatment efficacies in the advanced biliary tract cancer (BTC) were obscure, and a credible evaluation is urgently needed. Method A total of 6348 advanced BTC patients (ICC, intrahepatic cholangiocarcinoma, n = 1762; PHCC, perihilar cholangiocarcinoma, n = 1103; GBC, gallbladder cancer, n = 2580; DCC, distal cholangiocarcinoma, n = 538; AVC, carcinoma of Vater ampulla, n = 365) were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) process was carried out for less bias. Result The proportion of M1 patients in each subtype at first diagnosis was 26.4% (ICC), 37.2% (PHCC), 41. 0% (GBC), 24.5% (DCC), and 12.7% (AVC), and the constitution of DM sites in different subtypes varied apparently. Moreover, the survival of metastasis sites was different (P, Using a large population, we provided a detailed landscape about the DM mode of the advanced biliary tract cancer (BTC), found the survival differences among DM sites, and revealed the different chemotherapy efficacies in the BTC subtypes. The constitution and the survival of the DM sites varied significantly in different subtypes, and the chemotherapy efficacies manifested different among the subtypes.

Background Gallbladder cancer (GC) is a malignant disease characterized with highly cellular heterogeneity and poor prognosis. Determining the intratumoral heterogeneity and microenvironment (TME) can provide novel therapeutic strategies for GC. Methods We performed the single‐cell RNA sequencing on the primary and lymph node metastatic gallbladder tumors and the adjacent normal tissues of five patients. The transcriptomic atlas and ligand–receptor‐based intercellular communication networks of the single cells were characterized. Results The transcriptomic landscape of 24,887 single cells was obtained and characterized as 10 cellular clusters, including epithelial, neuroendocrine tumor cells, T&NK cells, B cells, RGS5+ fibroblasts, POSTN+ fibroblasts, PDGFRA+ fibroblasts, endothelial, myeloid cells, and mast cells. Different types of GC harbored distinct epithelial tumor subpopulations, and squamous cell carcinoma could be differentiated from adenocarcinoma cells. Abundant immune cells infiltrated into adenocarcinoma and squamous cell carcinoma, rather than neuroendocrine neoplasms, which showed significant enrichment of stromal cells. CD4+/FOXP3+ T‐reg and CD4+/CXCL13+ T helper cells with higher exhausting biomarkers, as well as a dynamic lineage transition of tumor‐associated macrophages from CCL20hi/CD163lo, CCL20lo/CD163hi to APOE+, were identified in GC tissues, suggesting the immunosuppressive and tumor‐promoting status of immune cells in TME. Two distinct endothelial cells (KDR+ and ACKR1+), which were involved in angiogenesis and lymphangiogenesis, showed remarkable ligand–receptor interactions with primary GC cells and macrophages in gallbladder tumors. Conclusions This study reveals a widespread reprogramming across multiple cell populations in GC progression, dissects the cellular heterogeneity and interactions in gallbladder TME, and provides potential therapeutic targets for GC., Abundant immune cells in adenocarcinoma and squamous cell carcinoma while stromal cells in neuroendocrine neoplasms were enriched.Immunosuppressive microenvironment characterized as exhausted T cells and APOE+ macrophages.Endothelial cells (KDR+ and ACKR1+) indicated that angiogenesis and lymphangiogenesis were involved in GC.There were remarkable ligand–receptor interactions between endothelial, primary GC cells, and macrophages.

Tumor‐infiltrating neutrophils (TIN) carry out quite significant but opposite functions in different cancers, and their function in biliary cancer has not been fully characterized. To investigate the prognostic significance of TIN in biliary cancer, a training set (n = 118) and a validation set (n = 127) were involved in this study. TIN were evaluated by immunohistochemical staining of CD66b, and then defined as low (neutrophils

We are glad to respond to the concerns of Drs. Levy and Terrault about our articles on the mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in HBeAg-positive mothers. We agree with Drs. Levy and Terrault that antiviral therapy of HBV during pregnancy could effectively decrease the MTCT, and this strategy has been recommended by WHO for pregnant women with a high viral load. However, the long-term influences of the abrupt cessation of antiretroviral drugs in mothers and prenatal exposure to antiviral drugs in newborns are not completely understood and are still under investigation. And not all pregnant mothers would accept this regiment due to the medication availability and individual willingness. It makes sense to study the influential factors on MTCT among mothers with high-risk transmission but not taking antiviral drugs. Despite the relatively large number of subjects included in our cohort (N = 857), post hoc power computation shows that the test efficacy is far from adequate to detect the association between delivery mode or feeding type and HBV MTCT. Therefore, we summarized the relevant studies to reach a relatively reasonable conclusion in HBsAg- and HBeAg-positive pregnant mothers not taking antiviral drugs. We provide an alternative option for HBsAg- and HBeAg-positive pregnant mothers who cannot access or defer to antiviral therapy during pregnancy to reduce the risk of HBV transmission to their offspring.

In this paper, the strain error of subset-based two-dimensional digital image correlation (DIC) is theoretically derived. Analytical solutions are provided to estimate the strain error. A dimensionless factor is proposed, namely the overlap magnifier, which reveals the dependency of the strain error on the DIC regularisation parameters, that is, subset size, step size and strain window size. The derived equations are validated numerically and experimentally. The estimated random strain error is in good accordance with the experimental data. The proposed derivation can be readily extended to stereo DIC.

This study presents a theoretical uncertainty quantification of displacement measurements by subset-based 2D-digital image correlation. A generalized solution to estimate the random error of displacement measurement is presented. The obtained solution suggests that the random error of displacement measurements is determined by the image noise, the summation of the intensity gradient in a subset, the subpixel part of displacement, and the interpolation scheme. The proposed method is validated with virtual digital image correlation tests.

In this work, we describe the evaluation of the stability and pharmacokinetics of cabazitaxel-loaded lipid microspheres (CTX-LM) prepared by high-pressure homogenization. Investigation of the physicochemical stability under different homogenization cycles and diverse sterilization times confirmed that 8 cycles at 800 bar and 121°C for 8 min were the optimal technological parameters. The beneficial effect of cholesterol on the physical stability of CTX-LM was confirmed and its mechanism of action was identified. The stability of CTX-LM using an aqueous isotonic glucose solution as a diluting agent was greater compared with using 0.9% NaCl solution as a result of an electric charge effect. CTX-LM are stable under freeze-thaw conditions and should not be exposed to high temperatures and protected from light during storage. Furthermore, all the changes in parameters were within an acceptable range at 4°C within 9 months, which supported the good long-term stability of CTX-LM. Finally, to compare the pharmacokinetics of CTX-LM with cabazitaxel-solution in vivo, a rapid, accurate UPLC-MS/MS method was developed and used to determine cabazitaxel in rat plasma after a single intravenous administration of 4 mg/kg. An obviously larger area under the curve (AUC) of CTX-LM was observed than that of CTX-solution, which will improve the antitumor efficacy of cabazitaxel. Practical applications: As a novel semisynthetic taxane, cabazitaxel has shown antitumour activity in a broad range of cell-lines and tumor models and has been approved in combination with prednisone for the treatment of patients with castration-resistant metastatic prostate cancer. However, serious undesirable effects in humans, such as anaphylactoid hypersensitivity reactions and peripheral neuropathy were produced by the addition of polysorbate 80 to commercial products. In this paper, CTX-LM was prepared by high-pressure homogenization in order to overcome the above drawbacks. The good stability and markedly higher AUC of CTX-LM may hasten their passage from a pre-clinical phase to a clinical trial phase and allow their production on a large scale. In this paper, cabazitaxel lipid microspheres exhibited a great stability and had a higher AUC than cabazitaxel solution.

To facilitate the preparation of lipid microspheres, norcantharimide, a C14 alkyl chain derivative of norcantharidin, was synthesized and its physicochemical properties were investigated. The N-14NCTDA loaded lipid microspheres (N-14NCTDA LMs) were prepared by a high-pressure homogenization method and characterized in terms of size, zeta-potential, encapsulation efficiency and stability. The apparent oil–water partition coefficient of N-14NCTDA (Log P > 2) was considerably enhanced in comparison to NCTD (Log P (−1.06), pH = 7.4). After optimization of the lipid microsphere formulation, the particle size distribution, zeta-potential and entrapment efficacy were determined to be 189.2 ± 49.8 nm, −26.78 ± 1.03 mV, and 98.4 ± 0.38%, respectively. High physical and chemical stability was demonstrated in accelerated stability test. A pharmacokinetic study was carried out in rats after intravenous administration of N-14NCTDA LMs and N-14NCTDA solution. Their pharmacokinetic profiles were similar with no significant differences in main parameters. Nevertheless, it was noteworthy that a greatly prolonged half-life and higher Vss was obtained for N-14NCTDA LMs compared with NCTD loaded lipid microspheres (NCTD LMs). Therefore, the N-14NCTDA LMs with high encapsulation efficiency and high stability are superior for the treatment of cancer, not only due to reduced venous irritation, but also due to prolonged half-life. Practical applications: Norcantharidin (NCTD) has been shown to be effective against cancer, especially against primary hepatic carcinoma, but its application is limited by severe renal toxicity and short half-life. Compared to common injection preparations, lipid microspheres loaded with NCTD lead to greatly reduced venous irritation but problems with low encapsulation efficiency, short half-life and high kidney toxicity have not been solved. N-14NCTDA is a new synthetic chemotherapeutic agent, which displayed good broad spectrum cytotoxicity compared with NCTD. In this preformulation study we show that N-14NCTDA is a promising alternative to NCTD. Significantly enhanced stability and prolonged half-life were obtained for N-14NCTDA LMs compared with NCDT LMs.

Cortex Phellodendri is a typical Chinese herb with a large number of alkaloids existing in all parts of it. The most common methods for screening and isolating alkaloids are mostly labor intensive and time consuming. In this study, a new assay based upon ultrafiltration liquid chromatography was developed for the rapid screening of ligands for α-glucosidase and xanthine oxidase. The C. Phellodendri extract was found to contain two alkaloids with both α-glucosidase- and xanthine oxidase binding activities and one lactone with α-glucosidase-binding activity. Subsequently, with the help of high-speed countercurrent chromatography, the specific binding ligands including palmatine, berberine, and obaculactone with purities of 97.38, 96.12, and 96.08%, respectively, were successfully separated. An optimized low-toxicity two-phase solvent system composed of ethyl acetate/n-butanol/ethanol/water (3.5:1.7:0.5:5, v/v/v/v) was used to isolate the three compounds mentioned above from C. Phellodendri. The targeted compounds were identified by liquid chromatography coupled with mass spectrometry and NMR spectroscopy. Therefore, ultrafiltration liquid chromatography combined with high-speed countercurrent chromatography is not only a powerful tool for screening and isolating α-glucosidase and xanthine oxidase inhibitors in complex samples but is also a useful platform for discovering bioactive compounds for the prevention and treatment of diabetes mellitus and gout.

A multi-camera stereo digital image correlation (MC-DIC) set-up is presented to obtain full displacement and strain fields of a sheet-metal specimen subjected to an Erichsen test. The set-up is composed of several conventional stereo DIC systems (two camera set-up), each of which tracks the deformation of an aspect of the specimen. The individual measurements, including the geometries and the displacements, are then converted to the same reference frame to integrate into a global view. Afterwards, the strain is calculated based on the composed displacement field. It is found that the geometry and the displacement fields of the bulged specimen are ideally stitched, and smooth strain fields are obtained. The influences of the reference frame transformation and the stitching procedure on the MC-DIC measurement are investigated. A rigid motion test is performed to validate the displacement measurement. It is discussed that the global field is more reliable than the individual measurements for this test set-up.