Structural identification and anti-neuroinflammatory effects of a pectin-arabinoglucuronogalactan complex, AOPB-1-1, isolated from Asparagus officinalis.

Asparagus officinalis L. is a horticultural crop that contains a variety of bioactive compounds with anti-inflammatory effects. Aqueous extracts of A. officinalis can noticeably improve the learning and memory function of model mice. Herein, a pectin-arabinoglucuronogalactan complex (AOPB-1-1) with a relative molecular weight of 90.8 kDa was isolated from A. officinalis. The repeating structural unit of AOPB-1-1 was identified through monosaccharide composition, methylation analysis, uronic acid reduction, partial acid hydrolysis, and nuclear magnetic resonance spectroscopy. AOPB-1-1 contains the rhamnogalacturonan-I (RG-I) domain of pectin polysaccharides (PPs) and arabinoglucuronogalactan (AGG) regions. The backbone of the AGG region is composed of →3,6)-ß-D-Galp-(1→ and →4)-ß-D-Glcp-(1→ residues substituted at the 4-position to the →4)-α-D-GalAp-(1→ residues of the RG-I main chain. The anti-neuroinflammatory activity of AOPB-1-1 suggests that it can significantly reduce the content of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and inhibit the expression of inflammatory genes including cyclooxygenase-2 (COX2), nitric oxide synthase (iNOS), TNF-α, IL-6, and interleukin-1ß (IL-1ß) in LPS-stimulated BV2 cells. Furthermore, its inhibitory effects on TNF-α and IL-6 levels were even better than those of minocycline. The significant anti-neuroinflammatory activity of AOPB-1-1 suggests its applicability as a therapeutic option for the treatment of Alzheimer's disease.

Integration of Ultrathin Hafnium Oxide with a Clean van der Waals Interface for Two-Dimensional Sandwich Heterostructure Electronics.

Integrating high-κ dielectrics with a small equivalent oxide thickness (EOT) with two-dimensional (2D) semiconductors for low-power consumption van der Waals (vdW) heterostructure electronics remains challenging in meeting both interface quality and dielectric property requirements. Here, we demonstrate the integration of ultrathin amorphous HfOx sandwiched within vdW heterostructures by the selective thermal oxidation of HfSe2 precursors. The self-cleaning process ensures a high-quality interface with a low interface state density of 1011-1012 cm-2 eV-1. The synthesized HfOx displays excellent dielectric properties with an EOT of ∼1.5 nm, i.e., a high κ of ∼16, an ultralow leakage current of 10-6 A/cm2, and an impressively high breakdown field of 9.5 MV/cm. This facilitates low-power consumption vdW heterostructure MoS2 transistors, demonstrating steep switching with a low subthreshold swing of 61 mV/decade. This one-step integration of high-κ dielectrics into vdW sandwich heterostructures holds immense potential for developing low-power consumption 2D electronics while meeting comprehensive dielectric requirements.

Global Scientific Trends in Continuous Renal Replacement Therapy from 2000 to 2023: A Bibliometric and Visual Analysis.

INTRODUCTION: Continuous renal replacement therapy (CRRT) is one of the most widely used blood purification and organ support methods in the ICU. However, the development process, the current status, hotspots, and future trends of CRRT remain unclear. METHOD: The WoSCC database was used to analyze CRRT research evolution and theme trends. VOSviewer was used to construct coauthorship, co-occurrence, co-citation, and network visualizations. CiteSpace is used to detect bursts for co-occurrence items. Several important subtopics were reviewed and discussed in more detail. RESULTS: Global publications increased from 56 in 2000 to 398 in 2023, a 710.71% increase. Blood Purification published the most manuscripts, followed by the International Journal of Artificial Organs. The USA, the San Bortolo Hospital, and Bellomo were the most productive and impactful institution, country, and author, respectively. Based on co-occurrence cluster analysis, five clusters emerged: (1) clinical applications and management of CRRT; (2) sepsis and CRRT; (3) CRRT anticoagulant management; (4) CRRT and antibiotic pharmacokinetics and pharmacodynamics; and (5) comparison of CRRT and intermittent hemodialysis. COVID-19, initiation, ECOMO, cefepime, guidelines, cardiogenic shock, biomarker, and outcome were the latest high-frequency keywords or strongest bursts, indicating the emerging frontiers of CRRT. CONCLUSIONS: There has been widespread publication and citation of CRRT research in the past 2 decades. We provide an overview of current trends, global collaboration patterns, basic knowledge, research hotspots, and emerging frontiers.

Ultrafast and selective capture of 99TcO4-/ReO4- from wastewater by hyper-branched quaternary ammonium group-functionalized resin.

99Tc primarily exists high mobility in the natural aqueous environment due to its extremely high solubility and non-complexing features, which can easily cause radioactive pollution. We herein report a general strategy for constructing a novel resin (SiPAN-PEI) with multiple positive charges nitrogen, exhibiting ultrafast adsorption kinetics (< 3 min), superior adsorption capacities (463.96 mg g-1), and excellent selectivity in the presence of excess competitive anions, which exceed those of most commercial resins. Moreover, based on impressive structure stability in extreme conditions, SiPAN-PEI can still maintain superior adsorption abilities after suffering irradiation, calcination, and immersion in strong acid. In addition, the separation performance kept excellently after five loading-washing-eluting cycles and the total adsorption ratio can still reach 97 %. Outstandingly, SiPAN-PEI can remove most of ReO4- from simulated nuclear wastewater through a sequential injection automatic separation system and can reduce the concentration of ReO4- to the maximum concentration standard set by the World Health Organization (WHO) in a short time. Leveraging density functional theory calculations and other characteristics clearly elucidated adsorption mechanism of anion-exchange between Cl- and TcO4-/ReO4-. In terms of superior adsorption property, SiPAN-PEI is demonstrated to be a pretty candidate for 99Tc elimination from wastewater.

Interlayer Coupling in Anisotropic/Isotropic Van der Waals Heterostructures of ReS2 and WS2.

Van der Waals (vdW) heterostructures are composed of atomically thin layers assembled through weak (vdW) force, which have opened a new era for integrating materials with distinct properties and specific applications. However, few studies have focused on whether and how anisotropic materials affect heterostructure system. The study introduces anisotropic and isotropic materials in a heterojunction system to change the in-plane symmetry, offering a new degree of freedom for modulating its properties. The sample is fabricated by manually stacking ReS2 and WS2 flakes prepared by mechanical exfoliation. Raman spectra and photoluminescence measurements confirm the formation of an effective heterojunction, indicating interlayer coupling of the system. The anisotropy and asymmetry of the WS2 -ReS2 heterostructure system can be adjusted by the introduction of isotropic WS2 and anisotropic ReS2 , which can be proved by the change of the polarized Raman pattern. In the transient absorption measurement, the transient absorption spectra of WS2 -ReS2 heterostructure are red-shifted compared to those of WS2 monolayer, and the charge transfer is observed in the heterostructure. These results show the potential of anisotropic 2D materials in anisotropy modulation of heterostructures, which may promote future electronic or photonic application.

Prevalence of developmental dysplasia of the hip (DDH) in infants: a systematic review and meta-analysis.

OBJECTIVE: To estimate the prevalence of developmental dysplasia of the hip (DDH) in infants with a systematic review and meta-analysis. METHOD: A literature search was conducted in April 2023, using databases such as Cochrane Library, PubMed, MEDLINE, CNKI, and SinoMed, without language restrictions. Eligible studies included cross-sectional studies reporting the prevalence of DDH among infants aged 0-12 months. Two independent reviewers manually selected and coded the studies, with any disagreements resolved by a third reviewer. Meta-analysis was performed using a random-effects model to calculate the prevalence of DDH. Regression analysis examined the trend of DDH prevalence, and stratification analysis explored heterogeneity between studies. RESULTS: A total of 65 studies involving 3 451 682 infants were included in the meta-analysis. None of the studies were classified as high quality, four were medium-to-high quality, 50 were low-to-medium quality, and eight were low quality. The pooled prevalence of DDH was 1.40% (95% CI: 0.86 to 2.28, I2=100%), and prevalence of dysplasia, subluxation, and dislocation was 1.45% (95% CI: 0.93 to 2.24, I2=97%), 0.37% (95% CI: 0.22 to 0.60, I2=94%), and 0.21% (95% CI: 0.13 to 0.34, I2=92%), respectively. Notably, the overall prevalence has a slight upward trend in the last three decades (ß=0.24, p=0.35), but the dysplasia was downward trend (ß=-0.48, p<0.01). Girls have higher risk of DDH than boys (1.46% vs 0.66%; Q=5.83, df=1, p=0.02). There were no significant differences based on gender, country, setting, or screening technique. CONCLUSION: The prevalence of DDH among infants is approximately one in a 100, with girls being at higher risk. Though the prevalence of dysplasia has decreased, there is a slight upward trend in overall DDH. Therefore, routine screening for DDH in infants is recommended to prevent more serious developmental problems.

Curculigo orchioides polysaccharide COP70-1 stimulates osteogenic differentiation of MC3T3-E1 cells by activating the BMP and Wnt signaling pathways.

The crude polysaccharide CO70 isolated from Curculigo orchioides could alleviate ovariectomy-induced osteoporosis in rats. To clarify the bioactive components, a new heteropolysaccharide (COP70-1) was purified from CO70 in this study, which was consisted of ß-D-Manp-(1→, →4)-α-D-Glcp-(1→, →4)-ß-D-Manp-(1→, →3,4)-ß-D-Manp-(1→, →4,6)-ß-D-Manp-(1→, and →4,6)-α-D-Galp-(1→. COP70-1 significantly promoted the osteoblastic differentiation of MC3T3-E1 cells through improving alkaline phosphatase activity, the deposition of calcium as well as up-regulating the expression of osteogenic markers (RUNX2, OSX, BSP, OCN, and OPN). Furthermore, COP70-1 stimulated the expression of critical transcription factors of the BMP and Wnt pathways, including BMP2, p-SMAD1, active-ß-catenin, p-GSK-3ß, and LEF-1. In addition, LDN (BMP pathway inhibitor) and DKK-1 (Wnt pathway inhibitor) suppressed the COP70-1-induced osteogenic differentiation of MC3T3-E1 cells. Therefore, COP70-1 was one of the bioactive constituents of C. orchioides for targeting osteoblasts to treat osteoporosis by triggering BMP/Smad and Wnt/ß-catenin pathways.

Influences of Jujube Witches' Broom (JWB) Phytoplasma Infection and Oxytetracycline Hydrochloride Treatment on the Gene Expression Profiling in Jujube.

Jujube witches' broom disease (JWB), caused by Candidatus Phytoplasma ziziphi, is the most destructive phytoplasma disease threatening the jujube industry. Tetracycline derivatives treatments have been validated to be capable of recovering jujube trees from phytoplasma infection. In this study, we reported that oxytetracycline hydrochloride (OTC-HCl) trunk injection treatment could recover more than 86% of mild JWB-diseased trees. In order to explore the underlying molecular mechanism, comparative transcriptomic analysis of healthy control (C group), JWB-diseased (D group) and OTC-HCl treated JWB-diseased (T group) jujube leaves was performed. In total, 755 differentially expressed genes (DEGs), including 488 in 'C vs. D', 345 in 'D vs. T' and 94 in 'C vs. T', were identified. Gene enrichment analysis revealed that these DEGs were mainly involved in DNA and RNA metabolisms, signaling, photosynthesis, plant hormone metabolism and transduction, primary and secondary metabolisms, their transportations, etc. Notably, most of the DEGs identified in 'C vs. D' displayed adverse change patterns in 'D vs. T', suggesting that the expression of these genes was restored after OTC-HCl treatment. Our study revealed the influences of JWB phytoplasma infection and OTC-HCl treatment on gene expression profiling in jujube and would be helpful for understanding the chemotherapy effects of OTC-HCl on JWB-diseased jujube.

Construction and Manipulation of Serial Gradient Dilution Array on a Microfluidic Slipchip for Screening and Characterizing Inhibitors against Human Pancreatic Lipase.

Obesity is one of the foremost public health concerns. Human pancreatic lipase (hPL), a crucial digestive enzyme responsible for the digestion of dietary lipids in humans, has been validated as an important therapeutic target for preventing and treating obesity. The serial dilution technique is commonly used to generate solutions with different concentrations and can be easily modified for drug screening. Conventional serial gradient dilution is often performed with tedious multiple manual pipetting steps, where it is difficult to precisely control fluidic volumes at low microliter levels. Herein, we presented a microfluidic SlipChip that enabled formation and manipulation of serial dilution array in an instrument-free manner. With simple slipping steps, the compound solution could be diluted to seven gradients with the dilution ratio of 1:1 and co-incubated with the enzyme (hPL)-substrate system for screening the anti-hPL potentials. To ensure complete mixing of solution and diluent during continuous dilution, we established a numerical simulation model and conducted an ink mixing experiment to determine the mixing time. Furthermore, we also demonstrated the serial dilution ability of the proposed SlipChip using standard fluorescent dye. As a proof of concept, we tested this microfluidic SlipChip using one marketed anti-obesity drug (Orlistat) and two natural products (1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose (PGG) and sciadopitysin) with anti-hPL potentials. The IC50 values of these agents were calculated as 11.69 nM, 8.22 nM and 0.80 µM, for Orlistat, PGG and sciadopitysin, respectively, which were consistent with the results obtained by conventional biochemical assay.

Controllable Oxidation of ZrS2 to Prepare High-κ, Single-Crystal m-ZrO2 for 2D Electronics.

High-κ materials that exhibit large permittivity and band gaps are needed as gate dielectrics to enhance capacitance and prevent leakage current in downsized technology nodes. Among these, monoclinic ZrO2 (m-ZrO2 ) shows good potential because of its inertness and high-κ with respect to SiO2 , but a method to produce ultrathin single crystal is lacking. Here, the controllable preparation of ultrathin m-ZrO2 single crystals via the in situ thermal oxidation of ZrS2 is achieved. As-grown m-ZrO2 presents an equivalent oxide thickness of ≈0.29 nm, a high dielectric constant of ≈19, and a breakdown voltage (EBD ) of ≈7.22 MV cm-1 . MoS2 field effect transistor (FET) by using m-ZrO2 as a dielectric layer shows comparable mobility to that using SiO2 dielectric. The ultraclean interface of m-ZrO2 /MoS2 and high crystalline quality of m-ZrO2 lead to negligible hysteresis in transfer curves. Single crystal m-ZrO2 dielectric shows potential application in digital complementary metal oxidesemiconductor (CMOS) logic FET.

Ultrafast and selective separation of 99mTc from molybdenum matrix using DBDGA deliberately tailored macrocyclic crown-ethers.

Technetium-99m (99mTc) is an important medical radionuclide. Due to the crisis in supply of molybdenum-99 (99Mo), production of 99mTc directly via the 100Mo (p, 2 n) reaction by cyclotron was proposed. In this process, the most critical challenge is to rapidly and efficiently separate 99mTc from high concentration of molybdenum. In this work, a novel ligand, bis(N,N-dibutyldiglycolamide)dibenzo-18-crown-6 (BisDBDGA-DB18C6) was successfully synthesized and used for extraction of TcO4- /ReO4- from molybdenum. The results demonstrated that BisDBDGA-DB18C6 expressed excellent selectivity for TcO4- with a high separation factor of 1.6 × 105 against Mo, a fast extraction kinetic (within 45 s), and a high extraction capacity of 211 mmol ReO4- (99TcO4-)/per mole of extractant. The extraction mechanism was proposed as a co-interaction of macrocyclic crown ether and N,N-dibutyldiglycolamide group through slope analysis, FT-IR, ESI-MS, 1H NMR titration and theory calculations. Importantly, 99Tc in the organic phase can be quantitatively (> 99%) and easily back-extracted using deionized water, which can be directly used for medical applications.

Sequential Separation of Iodine Species in Nitric Acid Media for Speciation Analysis of 129I in a PUREX Process of Spent Nuclear Fuel Reprocessing.

For efficient and accurate speciation analysis of 129I in the nitric acid solution of spent nuclear fuel in its reprocessing process, a sequential procedure for stepwise separation of different iodine species in 3 mol/L HNO3 was proposed based on the solvent extraction using CCl4 and mesitylene. Molecular iodine (I2) was first separated by solvent extraction using CCl4, and iodide (I-) remaining in the aqueous phase was oxidized to I2 by adding NaNO2 and then extracted to mesitylene. Finally, iodate (IO3-) was reduced to I2 using NH2OH·HCl and extracted to mesitylene. The separation efficiency of 98-99% for tracer amounts of 129I2, 129I-, and 129IO3- in 3 mol/L HNO3 and less than 2% crossover among different iodine species were achieved. The extraction process and mechanism of different iodine species in CCl4 and mesitylene were investigated, and the problem of crossover of different iodine species due to the low extraction efficiency of low concentration of iodine in nitric acid solution was solved. A direct transfer of IO3- from HNO3 to the mesitylene phase without conversion to I2 was observed, which was attributed to the iodination of mesitylene in the HNO3 medium. Addition of a stable iodine species carrier and repeated extraction significantly improved the separation efficiency of iodine species, making their quantitative separation achievable. This method provides an approach for speciation analysis of 129I in the acidic spent nuclear fuel solution, enabling us to investigate and control the behavior of volatile 129I in the spent nuclear fuel reprocessing process.

Enhanced removal of radioactive iodine anions from wastewater using modified bentonite: Experimental and theoretical study.

Efficient and cost-effective removal of radioactive iodine anions from contaminated water has become a crucial task and a great challenge for waste treatment and environmental remediation. Herein, we present hexadecylpyridinium chloride monohydrate modified bentonite (HDPy-bent) for the efficient and selective removal of iodine anions (I- and IO3-) from contaminated water. Batch experiments showed that HDPy-bent could remove more than 95% of I- and IO3- within 10 min, and had maximum I- and IO3- adsorption capacities of 80.0 and 50.2 mg/g, respectively. Competitive experiments indicated that HDPy-bent exhibited excellent I- and IO3- selectivity in the excessive presence of common concomitant anions including PO43-, SO42-, HCO3-, NO3-, Cl- (maximum mole ratio of anions vs iodine anions was ∼50,000). An anion exchange mechanism was proposed for the selective adsorption of iodine anions. Optimal adsorption structure of HDPy+/I- (IO3-) at atomic level and driving forces of the I- (IO3-) adsorption were calculated by density functional theory (DFT) simulations. Moreover, the good durability and reusability of the HDPy-bent has been demonstrated with 5 adsorption-desorption cycles. Dynamic column experiment also demonstrated that HDPy-bent exhibited excellent removal and fractional recovery capabilities towards I- and IO3- from simulated groundwater and environmental water samples. In conclusion, this work presents a promising adsorbent material for the decontamination of radioactive iodine anions from wastewater on a large scale.

Controlling Carrier Transport in Vertical MoTe2/MoS2 van der Waals Heterostructures.

Two-dimensional (2D) transition-metal dichalcogenide (TMDC)-based semiconducting van der Waals (vdW) heterostructures are considered as potential candidates for next-generation nanoelectronics due to their unique and tunable properties. Controlling the carrier type and band alignment in 2D TMDCs and their vdW heterostructures is critical for realizing heterojunctions with the desired performances and functionalities. In this report, controlling the carrier type and band alignment in a vertical MoTe2/MoS2 heterojunction is presented via thickness engineering and surface charge transfer doping. A highly rectifying p-n diode and a nonrectifying n-n junction are obtained with different MoTe2 thicknesses due to their different doping conditions. A vertical tunnel diode is subsequently achieved with a controlled oxygen plasma treatment, which selectively induces degenerate p-type doping to MoTe2, whereas the intrinsic n-type characteristic of MoS2 is maintained during the treatment. These techniques to realize multifunctional diodes are universal and applicable to emerging nanoelectronics based on 2D materials.

Charge-Ferroelectric Transition in Ultrathin Na0.5 Bi4.5 Ti4 O15 Flakes Probed via a Dual-Gated Full van der Waals Transistor.

Ferroelectric field-effect transistors (FeFETs) have recently attracted enormous attention owing to their applications in nonvolatile memories and low-power logic electronics. However, the current mainstream thin-film-based ferroelectrics lack good compatibility with the emergent 2D van der Waals (vdW) heterostructures. In this work, the synthesis of thin ferroelectric Na0.5 Bi4.5 Ti4 O15 (NBIT) flakes by a molten-salt method is reported. With a dry-transferred NBIT flake serving as the top-gate dielectric, dual-gate molybdenum disulfide (MoS2 ) FeFETs are fabricated in a full vdW stacking structure. Barrier-free graphene contacts allow the investigation of intrinsic carrier transport of MoS2 governed by lattice scattering. Thanks to the high dielectric constant of ≈94 in NBIT, a metal to insulator transition with a high electron concentration of 3.0 × 1013 cm-2 is achieved in MoS2 under top-gate modulation. The electron field-effect mobility as high as 182 cm2 V-1 s-1 at 88 K is obtained. The as-fabricated MoS2 FeFET exhibits clockwise hysteresis transfer curves that originate from charge trapping/release with either top-gate or back-gate modulation. Interestingly, hysteresis behavior can be controlled from clockwise to counterclockwise using dual-gate. A multifunctional device utilizing this unique property of NBIT, which is switchable electrostatically between short-term memory and nonvolatile ferroelectric memory, is envisaged.

Influence of γ-irradiation and oxygen conditions on the diffusion of I-125 in crushed Beishan granite.

The diffusion of iodine (labeled with 125I-) in compacted Beishan granite (BsG) was investigated using the in-diffusion capillary method at pH ~2.0 to ~11.0 under oxygen and irradiation conditions. With the advantages of simple and easy operation of the capillary diffusion devices, this work makes a preliminary investigation on the irradiation condition that cannot be performed by the traditional diffusion experiment. In this study, Da values of 125I as a tracer in the form of iodide were determined to investigate and assess the influence of irradiation and oxygen conditions, which must be considered in-situ environment of the geologic repository. The results indicate that capillary method is a simple and efficient method to study the diffusion behavior of radionuclides, which is a relatively feasible to quickly obtain the diffusion coefficient, especially for some special conditions, e.g., oxygen and irradiation conditions. The diffusion results showed that Da values of 125I- range from 1.4 × 10-10 to 1.5 × 10-9 m2∙s-1, which was much faster than other nuclides, such as 79Se (10-11 m2∙s-1). The batch adsorption experiments in this paper and related studies showed that the sorption could be neglected, i.e., 125I- is a weak adsorbent nuclide. Its diffusion and sorption process were hardly affected by pH、oxygen and irradiation conditions, which is very different from 79Se. Besides, ionic strength has a significant impact on the diffusion rate of 125I-, which is closely related to the double electric layer. Overall, this study indicates that natural BsG couldn't greatly attenuate the mobility of 125I- in the deep geologic repository and new retardation method or materials need to be explored.

Chemoradiation versus oesophagectomy for locally advanced oesophageal cancer in Chinese patients: study protocol for a randomised controlled trial.

BACKGROUND: Surgery is the gold standard treatment for local advanced disease, while definitive concurrent chemoradiotherapy (DCRT) is recommended for those who are medically unable to tolerate major surgery or medically fit patients who decline surgery. The primary aim of this trial is to compare the outcomes in Chinese patients with oesophageal squamous cell cancer with locally advanced resectable disease who have received either surgery or DCRT. METHODS/DESIGN: One hundred ninety-six patients with T1bN + M0 or T2-4aN0-2 M0 oesophageal squamous cell cancer will be randomised to the DCRT group or the surgery group. In the DCRT group, patients will be given intensity-modulated radiation therapy (IMRT) with 50 Gy/25 fractions and basic chemotherapy with 5-fluorouracil regimens. In the surgery group, patients will receive neoadjuvant chemoradiotherapy (NCRT) and standard oesophagectomy. Five years of follow-up will be scheduled for patients. The primary endpoints are 2-year/5-year overall survival; the secondary endpoints are 2-year/5-year progression-free survival, treatment-related adverse events and the patients' quality of life. The main evaluation methods include oesophagoscopy, endoscopic ultrasonography and biopsy, oesophageal barium meal, computed tomography, positron emission tomography-computed tomography, blood tests and questionnaires. DISCUSSION: The preponderant oesophageal cancer pathology type is dramatically different in western Caucasian and Asian oesophageal cancer patients: Caucasian patients present with 80% adenocarcinomas, and Asians patients present with 95% squamous cell carcinomas. This phenomenon needs more in-depth studies to elucidate the differences in these populations. Based on the results of this study, we will show whether DCRT will benefit patients more than oesophagectomy. This study will contribute more evidence to the management of oesophageal squamous cell cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02972372 . Registered on 26 November 2016.

Circulating microRNAs as novel potential diagnostic biomarkers for ovarian cancer: a systematic review and updated meta-analysis.

OBJECT: Ovarian cancer is the primary cause of cancer-associated deaths among gynaecological malignancies. Increasing evidence suggests that microRNAs may be potential biomarkers for the diagnosis and prognosis of cancer. In this study, we conducted a systematic review and meta-analysis to summarize the global research and to evaluate the overall diagnostic accuracy of miRNAs in detecting ovarian cancer. METHODS: A systematic literature search was conducted for relevant studies through July 20, 2017, in English databases (CENTRAL, MEDLINE, and EMBASE), the Grey reference database and Chinese databases. Statistical analysis was conducted using OpenMetaAnalyst, STATA 14.0 and RevMan 5.3. Pooled sensitivity, specificity, and other parameters were used to assess the overall miRNA assay performance using a bivariate random-effects model (BRM). Meta-regression and subgroup analyses were performed to dissect the heterogeneity. Sensitivity analysis was performed to assess the robustness of our analysis, and the publication bias of the selected studies was assessed using Deeks' funnel plot asymmetry test. RESULTS: Thirteen articles described 33 studies, including 1081 patients with ovarian cancer and 518 controls. The pooled results were as follows: sensitivity, 0.89 (95% CI: 0.84-0.93); specificity, 0.64 (95% CI: 0.56-0.72); positive likelihood ratio, 2.18 (95% CI: 1.89-2.51); negative likelihood ratio, 0.15 (95% CI: 0.11-0.22); and diagnostic odds ratio (DOR), 13.21 (95% CI: 9.00-19.38). We conducted subgroup analyses based on ethnicity, research design, and miRNA profiling and found that multiple miRNA panels were more accurate in detecting ovarian cancer, with a combined DOR of 30.06 (95% CI: 8.58-105.37). CONCLUSION: Per the meta-analysis, circulating miRNAs may be novel and non-invasive biomarkers for detecting ovarian cancer, particularly multiple miRNA panels, which have potential diagnostic value as screening tools in clinical practice.

Cell-free DNA in blood and urine as a diagnostic tool for bladder cancer: a meta-analysis.

OBJECTIVE: To assess the diagnostic performance of cell-free DNA assays in the detection of bladder cancer. PATIENTS AND METHODS: The quality of the studies included in this meta-analysis was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Statistical analyses were performed using the software RevMan 5.3 and Stata 14.0. We assessed the pooled sensitivity and specificity, positive/negative likelihood ratios (PLRs/NLRs), diagnostic odds ratios (DORs), and corresponding 95% confidence intervals (95% CIs). Summary receiver operating characteristic curve (ROC curve) and area under the curve (AUC) were used to summarize the overall test performance. Heterogeneity and publication bias were also examined. RESULTS: Eleven studies included 802 bladder cancer patients and 668 controls met the eligibility criteria. The overall diagnostic accuracy was measured as follows: sensitivity 0.71 (95% CI = 0.64-0.77), specificity 0.78 (95% CI = 0.70-0.85), PLR 3.3 (95% CI = 2.4-54.5), NLR 0.37 (95% CI = 0.30-0.46), DOR 9 (95% CI = 6-14), and AUC 0.80 (95% CI = 0.77-0.83). Subgroup analysis suggested that ethnicity significantly accounted for the heterogeneity of specificity. The Deeks' funnel plot asymmetry test (P = 0.97) suggested no potential publication bias. CONCLUSIONS: Cell-free DNA has a high diagnostic value in bladder cancer.

A highly integrated precision nanomedicine strategy to target esophageal squamous cell cancer molecularly and physically.

The prognosis of esophageal squamous cell carcinoma is poor. We hereby presented a highly integrated and clinically relevant precision nanomedicine strategy to target ESCC molecularly and physically for significant improvement of the treatment efficacy. We firstly identified PI3K overexpression in patient samples and its relation to poor patient survival. With our highly versatile tumor-targeted drug delivery platform (DCM), we were able to load a potent but toxic docetaxel (DTX) and a PI3K inhibitor (AZD8186) with favorable physical properties. The combination of the DTX-DCM and AZD8186-DCM showed a highly efficacious and synergistic anti-tumor effect and decreased hematotoxicity. A pro-apoptotic protein, Bax was significantly upregulated in ESCC cells treated with combination therapy compared to that with monotherapy. This study utilized a highly integrated precision nano-medicine strategy that combines the identification of cancer molecular target from human patients, precision drug delivery and effective combination therapy for the development of better ESCC treatment.