Acidity is a hallmark of malignant tumor, representing a very efficient mechanism of chemoresistance. Proton pump inhibitors (PPI) at high dosage have been shown to sensitize chemoresistant human ...tumor cells and tumors to cytotoxic molecules. The aim of this pilot study was to investigate the efficacy of PPI in improving the clinical outcome of docetaxel + cisplatin regimen in patients with metastatic breast cancer (MBC).
Patients enrolled were randomly assigned to three arms: Arm A, docetaxel 75 mg/m(2) followed by cisplatin 75 mg/m(2) on d4, repeated every 21 days with a maximum of 6 cycles; Arm B, the same chemotherapy preceded by three days esomeprazole (ESOM) 80 mg p.o. bid, beginning on d1 repeated weekly. Weekly intermittent administration of ESOM (3 days on 4 days off) was maintained up to maximum 66 weeks; Arm C, the same as Arm B with the only difference being dose of ESOM at 100 mg p.o. bid. The primary endpoint was response rate.
Ninety-four patients were randomly assigned and underwent at least one injection of chemotherapy. Response rates for arm A, B and C were 46.9, 71.0, and 64.5 %, respectively. Median TTP for arm A (n = 32), B (n = 31), C (n = 31) were 8.7, 9.4, and 9.7 months, respectively. A significant difference was observed between patients who had taken PPI and who not with ORR (67.7 % vs. 46.9 %, p = 0.049) and median TTP (9.7 months vs. 8.7 months, p = 0.045) corrected. Exploratory analysis showed that among 15 patients with triple negative breast cancer (TNBC), this difference was bigger with median TTP of 10.7 and 5.8 months, respectively (p = 0.011). PPI combination showed a marked effect on OS as well, while with a borderline significance (29.9 vs. 19.2 months, p = 0.090). No additional toxicity was observed with PPI.
The results of this pilot clinical trial showed that intermittent high dose PPI enhance the antitumor effects of chemotherapy in MBC patients without evidence of additional toxicity, which requires urgent validation in a multicenter, randomized, phase III trial.
Clinicaltrials.gov identifier: NCT01069081 .
Traumatic brain injury (TBI) is a dominant cause of death and permanent disability worldwide. Although TBI could significantly increase the proliferation of adult neural stem cells in the ...hippocampus, the survival and maturation of newborn cells is markedly low. Increasing evidence suggests that the secretome derived from mesenchymal stem cells (MSCs) would be an ideal alternative to MSC transplantation. The successive and microenvironmentally responsive secretion in MSCs may be critical for the functional benefits provided by transplanted MSCs after TBI. Therefore, it is reasonable to hypothesize that the signaling molecules secreted in response to local tissue damage can further facilitate the therapeutic effect of the MSC secretome. To simulate the complex microenvironment in the injured brain well, we used traumatically injured brain tissue extracts to pretreat umbilical cord mesenchymal stem cells (UCMSCs) in vitro and stereotaxically injected the secretome from traumatic injury‐preconditioned UCMSCs into the dentate gyrus of the hippocampus in a rat severe TBI model. The results revealed that compared with the normal secretome, the traumatic injury‐preconditioned secretome could significantly further promote the differentiation, migration, and maturation of newborn cells in the dentate gyrus and ultimately improve cognitive function after TBI. Cytokine antibody array suggested that the increased benefits of secretome administration were attributable to the newly produced proteins and up‐regulated molecules from the MSC secretome preconditioned by a traumatically injured microenvironment. Our study utilized the traumatic injury‐preconditioned secretome to amplify neurogenesis and improve cognitive recovery, suggesting this method may be a novel and safer candidate for nerve repair.
Cover Image for this issue: doi: 10.1111/jnc.14741
To most closely replicate the complex microenvironment in injured brain, we used extract of traumatic brain tissue to preconditioning umbilical cord mesenchymal stem cells (MSCs) in vitro, and stereotaxically injected these secretome into dentate gyrus of hippocampus in a rat severe Traumatic brain injury (TBI) model. We observed that traumatically preconditioning secretome could significantly further promote the differentiation, migration and maturation of newborn cells in dentate gyrus, and finally improved the cognitive function after TBI. Our study utilized the injury‐preconditioning secretome to inducibly amplify the neurogenesis and cognitive recovery, which can offers a novel and safer candidate for nerve repair.
Open Science: This manuscript was awarded with the Open Materials Badge
For more information see: https://cos.io/our-services/open-science-badges/
Cover Image for this issue: doi: 10.1111/jnc.14741
Abstract
Defect engineering is an effective strategy to improve the activity of two-dimensional molybdenum disulfide base planes toward electrocatalytic hydrogen evolution reaction. Here, we report a ...Frenkel-defected monolayer MoS
2
catalyst, in which a fraction of Mo atoms in MoS
2
spontaneously leave their places in the lattice, creating vacancies and becoming interstitials by lodging in nearby locations. Unique charge distributions are introduced in the MoS
2
surface planes, and those interstitial Mo atoms are more conducive to H adsorption, thus greatly promoting the HER activity of monolayer MoS
2
base planes. At the current density of 10 mA cm
−2
, the optimal Frenkel-defected monolayer MoS
2
exhibits a lower overpotential (164 mV) than either pristine monolayer MoS
2
surface plane (358 mV) or Pt-single-atom doped MoS
2
(211 mV). This work provides insights into the structure-property relationship of point-defected MoS
2
and highlights the advantages of Frenkel defects in tuning the catalytic performance of MoS
2
materials.
With the continuous development and improvement of the social system and structure, the scope of functions of colleges and universities, as market subjects, in participating in market activities ...continues to expand, and the logos of colleges and universities, as intangible assets of colleges and universities, can be transformed into tangible assets in market activities, and the economic value generated by them has brought considerable benefits to many speculators. The ensuing intellectual property rights dispute about the college logo is becoming more and more fierce. The Outline for Building a strong Intellectual Property Country (2021-2035) clearly proposes to strengthen the construction of an intellectual property protection system, which also provides a reference direction and expected construction for intellectual property protection in universities. This paper will make a simple analysis of the infringement of college logos through case analysis and literature review, and put forward corresponding objective and feasible solutions.
Accurately evaluating minimal residual disease (MRD) could facilitate early intervention and personalized adjuvant therapies. Here, using ultradeep targeted next-generation sequencing (NGS), we ...evaluate the clinical utility of circulating tumor DNA (ctDNA) for dynamic recurrence risk and adjuvant chemotherapy (ACT) benefit prediction in resected non-small cell lung cancer (NSCLC). Both postsurgical and post-ACT ctDNA positivity are significantly associated with worse recurrence-free survival. In stage II-III patients, the postsurgical ctDNA positive group benefit from ACT, while ctDNA negative patients have a low risk of relapse regardless of whether or not ACT is administered. During disease surveillance, ctDNA positivity precedes radiological recurrence by a median of 88 days. Using joint modeling of longitudinal ctDNA analysis and time-to-recurrence, we accurately predict patients' postsurgical 12-month and 15-month recurrence status. Our findings reveal longitudinal ctDNA analysis as a promising tool to detect MRD in NSCLC, and we show pioneering work of using postsurgical ctDNA status to guide ACT and applying joint modeling to dynamically predict recurrence risk, although the results need to be further confirmed in future studies.
Background. Patients with chronic hepatitis B (CHB) concomitant with nonalcoholic fatty liver disease (NAFLD) are increasing. Objectives. To identify pathological features that can be used to ...differentiate between chronic inflammation caused by CHB and that caused by NAFLD. Methods. Patients with CHB (n=31) needing antiviral treatment, NAFLD (n=50), or CHB-NAFLD (n=51) who underwent biopsy were retrospectively enrolled. Pathological characteristics of chronic inflammation were evaluated using the METAVIR scoring system. The rates of three pathological characteristics were first compared in patients with NAFLD and those with CHB, then compared after fibrosis matching, and were finally compared in CHB-NAFLD patients with different viral loads. Results. The rates of interface hepatitis over grade 2 and fibrosis over grade 2 were significantly higher in the CHB group than in the NAFLD group (100% vs. 4% and 80.6% vs. 22%; both P<0.0001), while no significant difference was observed in the rate of lobular inflammation over grade 2 between the two groups. After fibrosis matching, in patients with F0–2 fibrosis, the rate of interface hepatitis over grade 2 in CHB was significantly higher than that in NAFLD (100% vs. 0%; P<0.0001). In CHB-NAFLD patients with F0–2 fibrosis, the rate of interface hepatitis over grade 2 in cases with a high viral load was significantly higher than cases with a low viral load (66.6% vs. 0%; P<0.0001). The rate of lobular inflammation showed no difference between groups. Conclusion. Interface hepatitis over grade 2 can be used for the differential diagnosis of chronic inflammation associated with CHB or NAFLD in the early stage.
Marine-derived
fungi are productive sources of structurally unique and diverse bioactive secondary metabolites, representing a hot topic in natural product research. This review describes structural ...diversity, bioactivities and statistical research of 452 new natural products from marine-derived
fungi covering 2021 to 2023. Sediments are the main sources of marine-derived
fungi for producing nearly 56% new natural products. Polyketides, alkaloids, and terpenoids displayed diverse biological activities and are the major contributors to antibacterial activity, cytotoxicity, anti-inflammatory and enzyme inhibitory capacities. Polyketides had higher proportions of new bioactive compounds in new compounds than other chemical classes. The characteristics of studies in recent years are presented.
The development of n-type high-performance PbTe thermoelectric materials for matching its p-type counterparts is an urgent matter to expand its practical applications. Here, we introduce Ag2Te into ...n-type Pb0.975Cr0.025Te for achieving a high peak figure of merit of 1.5 at 773 K. Such a high value is attributed to the synergistic optimization of carrier and phonon transports by Ag2Te introducing and the dynamic doping of Ag. From the detailed structure and property analysis, we found that Ag2Te nanoprecipitates establish coherent interfaces and hence potential barriers with the matrix to induce energy-dependent carrier scattering and maintain relatively high carrier mobility, leading to an optimal electrical-transport properties over a wide temperature range. Moreover, we employ comprehensive electron microscopy investigations and approximate Debye-Callaway model to reveal the origin of the significantly reduced lattice thermal conductivity in Ag2Te-alloyed Pb0.975Cr0.025Te. The strategies used here provide an effective method for designing high-performance thermoelectric material systems.
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Ag2Te nanoprecipitates introduce dynamic doping, energy filtering, and intense phonon scattering to simultaneously optimize the electrical and thermal properties of n-type Ag2Te-alloyed Pb0.975Cr0.025Te, leading to a realization of high thermoelectric performance.
•Dynamic doping and energy filtering of Ag2Te nanoprecipitates optimize carrier transport.•A comprehensive investigation of the phonon scattering sources in Ag2Te-alloyed Pb0.975Cr0.025Te.•Remarkable peak ZT of ~1.5 is achieved in Pb0.975Cr0.025Te-1.5% Ag2Te.
Copper-containing bioactive glass/eggshell membrane nanocomposites with uniform BG nanocoatings (thickness: 40nm) improving antibacterial activity, angiogenic ability of HUVECs in vitro and wound ...healing quality in vivo. Display omitted
Effectively stimulating angiogenesis and avoiding wound infection are great challenges in wound care management. Designing new healing dressings with requisite angiogenic capacity and antibacterial performance is of particular significance. In order to achieve this aim, we prepared a copper (Cu)-containing bioactive glass nanocoating (40–50nm) with uniform nanostructure on natural eggshell membrane (Cu-BG/ESM) by the pulsed laser deposition (PLD) technique. The surface physicochemical properties including hydrophilicity and hardness of ESM were significantly improved after depositing Cu-BG nanocoatings. Meanwhile, 5Cu-BG/ESM films containing 5mol% Cu stimulated proangiogenesis by improving vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α protein secretion as well as angiogenesis-related gene expression (VEGF, HIF-1α, VEGF receptor 2 (KDR) and endothelial nitric oxide (eNos)) of human umbilical vein endothelial cells (HUVECs). When used to treat full-thickness skin defects in mice, 5Cu-BG/ESM films enhanced the healing quality as confirmed by the significantly improved angiogenesis (as indicated by CD31 expression) and formation of continuous and uniform epidermis layer in vivo. Furthermore, 5Cu-BG/ESM films could maintain a sustained release of Cu2+ ions and distinctly inhibited the viability of bacteria (Escherichia coli). The results indicate that Cu2+ ions released from Cu-BG/ESM nanocomposite films play an important role for improving both angiogenesis and antibacterial activity and the prepared nanocomposite films combined Cu-containing BG nanocoatings with ESM are a promising biomaterial for wound healing application.
Designing new healing dressings with requisite angiogenic capacity and antibacterial performance is of particular significance in wound care management. In our study, we successfully prepared copper-containing bioactive glass/eggshell membrane (Cu-BG/ESM) nanocomposites with uniform bioactive glass nanocoatings by using pulsed laser deposition (PLD) technology. Due to the deposited Cu-BG nanocoatings on the surface of ESM, Cu-BG/ESM nanocomposites possessed significantly improved physicochemical and biological properties, including surface hydrophilicity, hardness, antibacterial ability, angiogenesis rate in vitro and wound healing quality in vivo as compared to pure ESM and BG/ESM films. Our study showed that prepared nanocoatings on Cu-BG/ESM nanocomposites offer a beneficial carrier for sustained release of Cu2+ ions which played a key role for improving both angiogenesis and antibacterial activity. The prepared nanocomposites combined Cu-containing BG nanocoatings with ESM are a promising biomaterial for wound healing application.
Objective
We aimed to analyze the risk factors and to establish a predictive tool for the occurrence of bloodstream infections (BSI) in patients with cirrhosis.
Methods
A total of 2888 patients with ...cirrhosis were retrospectively included. Multivariate analysis for risk factors of BSI were tested using logistic regression. Multivariate logistic regression was validated using five-fold cross-validation.
Results
Variables that were independently associated with incidence of BSI were white blood cell count (odds ratio OR = 1.094, 95% confidence interval CI 1.063–1.127), C-reactive protein (OR = 1.005, 95% CI 1.002–1.008), total bilirubin (OR = 1.003, 95% CI 1.002–1.004), and previous antimicrobial exposure (OR = 4.556, 95% CI 3.369–6.160); albumin (OR = 0.904, 95% CI 0.883–0.926), platelet count (OR = 0.996, 95% CI 0.994–0.998), and serum creatinine (OR = 0.989, 95% CI 0.985–0.994) were associated with lower odds of BSI. The area under receiver operating characteristic (ROC) curve of the risk assessment scale was 0.850, and its sensitivity and specificity were 0.762 and 0.801, respectively. There was no significant difference between the ROC curves of cross-validation and risk assessment.
Conclusions
We developed a predictive tool for BSI in patients with cirrhosis, which could help with early identification of such episodes at admission, to improve outcome in these patients.
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