Storage of plasma-derived exosomes: evaluation of anticoagulant use and preserving temperatures.

Exosomes carry large cargo of proteins, lipids, and nucleic acids, serving as versatile biomarkers for disease diagnosis and vehicles for drug delivery. However, up to date, no well recognized standard procedures for exosome storage were available for clinical application. This study aimed to determine the optimal storage conditions and the anticoagulants for plasma-derived exosome isolation. Fresh whole blood samples were collected from healthy participants and preserved in four different anticoagulants including sodium citrate (SC1/4), sodium citrate (SC1/9), lithium heparin (LH), or Ethylenediamine tetraacetic acid (EDTA), respectively. Exosomes were extracted from the plasma by differential ultracentrifugation and stored at three different temperatures, 4°C, -20°C or - 80°C for a duration ranging from one week to six months. All plasma samples for storage conditions comparison were pretreated with LH anticoagulant. Exosome features including morphological characteristics, pariticles size diameter, and surface protein profiles (TSG101, CD63, CD81, CD9, CALNEXIN) were assessed by transmission electron microscopy, Nanoparticle Tracking Analysis, and Western Blotting, respectively. Exosomes preserved in LH and SC1/4 group tended to remain intact microstructure with highly abundant protein biomarkers. Exosomes stored at 4°C for short time were prone to be more stable compared to thos at -80°C. Exosomes stored in plasma were superior in terms of ultrastructure, size diameter and surface protein expression to those stored in PBS. In conclusion, plasma-dervied exosome characteristics strictly depend on the anticoagulants and storage temperature and duration.

What is the context? Effective isolation of exosomes is a prerequisite for subsequent investigation into its involvemnt in disease development as well as potentialtherapeutic applications.Anticoagulants, storage temperature and durations might change the microscopical structure, integrity and also the stability of plasma-derived exosomes. However, no internationally recognized standard of exosome storage procedure was available for clinical use.What is new? Our finding evaluated the effect of anticoagulants and storage on plasma exosome characteristics.Exosomes isolated from plasma preserved with Li-heparin and sodium citrate (1/4) showed better physical properties and surface marker protein expression.Isolated exosomes appeared more stable in a short time for 4°C compared to −80°C. Storage of exosomes in plasma showed better physical properties and surface marker protein expression than in PBS.What is the impact? Our findings inform the significance of standardizing procedure of exosome isolation and preservation.

Immunohistochemistry screening for TP53 mutation in myeloid neoplasms in AZF-fixed bone marrow biopsies.

TP53 mutational status in myeloid neoplasms is prognostic and in acute myeloid leukaemia (AML) may lead to alternative induction therapy; therefore, rapid assessment is necessary for precision treatment. Assessment of multiple prognostic genes by next generation sequencing in AML is standard of care, but the turn-around time often cannot support rapid clinical decision making. Studies in haematological neoplasms suggest p53 immunohistochemistry (IHC) correlates with TP53 mutational status, but they have used variable criteria to define TP53 overexpression. p53 IHC was performed and interpreted on AZF-fixed, acid decalcified bone marrow biopsies on 47 cases of clonal myeloid neoplasms with TP53 mutations between 2016 and 2019 and 16 control samples. Results were scored by manual and digital analysis. Most TP53-mutated cases (81%) overexpressed p53 by digital analysis and manual analysis gave similar results. Among the nine TP53-mutated IHC-negative cases, seven (78%) were truncating mutations and two (22%) were single-hit missense mutations. Using a digital cut-off of at least 3% ≥1+ positive nuclei, the sensitivity and specificity are 81% and 100%; cases with loss-of-function mutations were more likely to be negative. In this cohort, p53 immunopositivity correlated with TP53 mutational status, especially missense mutations, with excellent specificity. Truncating TP53 mutations explain most IHC-negative cases, impacting the sensitivity. We demonstrate that p53 IHC can screen for TP53 mutations allowing quicker treatment decisions for most patients. However, not all patients will be identified, so molecular studies are required. Furthermore, cut-offs for positivity vary in the literature, consequently laboratories should independently validate their processes before adopting p53 IHC for clinical use. p53 IHC performs well to screen for TP53 mutations in AZF-fixed bone marrow. Performance in our setting differs from the literature, which shows variability of pre-analytic factors and cut-offs used to screen for TP53 mutations. Each laboratory should validate p53 IHC to screen for TP53 mutations in their unique setting.

Observation of giant room-temperature anisotropic magnetoresistance in the topological insulator ß-Ag2Te.

Achieving room-temperature high anisotropic magnetoresistance ratios is highly desirable for magnetic sensors with scaled supply voltages and high sensitivities. However, the ratios in heterojunction-free thin films are currently limited to only a few percent at room temperature. Here, we observe a high anisotropic magnetoresistance ratio of -39% and a giant planar Hall effect (520 µΩ⋅cm) at room temperature under 9 T in ß-Ag2Te crystals grown by chemical vapor deposition. We propose a theoretical model of anisotropic scattering - induced by a Dirac cone tilt and modulated by intrinsic properties of effective mass and sound velocity - as a possible origin. Moreover, small-size angle sensors with a Wheatstone bridge configuration were fabricated using the synthesized ß-Ag2Te crystals. The sensors exhibited high output response (240 mV/V), high angle sensitivity (4.2 mV/V/°) and small angle error (<1°). Our work translates the developments in topological insulators to a broader impact on practical applications such as high-field magnetic and angle sensors.

Brain-Type Glycogen Phosphorylase (PYGB) in the Pathologies of Diseases: A Systematic Review.

Glycogen metabolism is a form of crucial metabolic reprogramming in cells. PYGB, the brain-type glycogen phosphorylase (GP), serves as the rate-limiting enzyme of glycogen catabolism. Evidence is mounting for the association of PYGB with diverse human diseases. This review covers the advancements in PYGB research across a range of diseases, including cancer, cardiovascular diseases, metabolic diseases, nervous system diseases, and other diseases, providing a succinct overview of how PYGB functions as a critical factor in both physiological and pathological processes. We present the latest progress in PYGB in the diagnosis and treatment of various diseases and discuss the current limitations and future prospects of this novel and promising target.

Above-Room-Temperature Ferromagnetism in Copper-Doped Two-Dimensional Chromium-Based Nanosheets.

Two-dimensional ferromagnetic materials (2D-FMs) are expected to become ideal candidates for low-power, high-density information storage in next-generation spintronics devices due to their atomically ultrathin and intriguing magnetic properties. However, 2D-FMs with room-temperature Curie temperatures (Tc) are still rarely reported, which greatly hinders their research progress and practical applications. Herein, ultrathin Cu-doped Cr7Te8 FMs were successfully prepared and can achieve above-room-temperature ferromagnetism with perpendicular magnetic anisotropy via a facile chemical vapor deposition (CVD) method, which can be controlled down to an atomic thin layer of ∼3.4 nm. STEM-EDX quantitative analysis shows that the proportion of Cu to metal atoms is ∼5%. Moreover, based on the anomalous Hall effect (AHE) measurements in a six-terminal Hall bar device without any encapsulation as well as an out-of-plane magnetic field, the maximum Tc achieved ∼315 K when the thickness of the sample is ∼28.8 nm; even the ultrathin 7.6 nm sample possessed a near-room-temperature Tc of ∼275 K. Meanwhile, theoretical calculations elucidated the mechanism of the ferromagnetic enhancement of Cu-doped Cr7Te8 nanosheets. More importantly, the ferromagnetism of CVD-synthesized Cu-doped CrSe nanosheets can also be maintained above room temperature. Our work broadens the scope on room-temperature ferromagnets and their heterojunctions, promoting fundamental research and practical applications in next-generation spintronics.

Xiaotan Sanjie recipe, a compound Chinese herbal medicine, inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation.

OBJECTIVE: Xiaotan Sanjie recipe (XTSJ), a Chinese herbal compound medicine, exerts a significant inhibitory effect on gastric cancer (GC) metastasis. This work investigated the mechanism underlying the XTSJ-mediated inhibition of GC metastasis. METHODS: The effect of XTSJ on GC metastasis and the associated mechanism were investigated in vitro, using GC cell lines, and in vivo, using a GC mouse model, by focusing on the expression of Glc-N-Ac-transferase V (GnT-V; encoded by MGAT5). RESULTS: The migration and invasion ability of GC cells decreased significantly after XTSJ administration, which confirmed the efficacy of XTSJ in treating GC in vitro. XTSJ increased the accumulation of E-cadherin at junctions between GC cells, which was reversed by MGAT5 overexpression. XTSJ administration and MGAT5 knockdown alleviated the structural abnormality of the cell-cell junctions, while MGAT5 overexpression had the opposite effect. MGAT5 knockdown and XTSJ treatment also significantly increased the accumulation of proteins associated with the E-cadherin-mediated adherens junction complex. Furthermore, the expression of MGAT5 was significantly lower in the lungs of BGC-823-MGAT5 + XTSJ mice than in those of BGC-823-MGAT5 + solvent mice, indicating that the ability of gastric tumors to metastasize to the lung was decreased in vivo following XTSJ treatment. CONCLUSION: XTSJ prevented GC metastasis by inhibiting the GnT-V-mediated E-cadherin glycosylation and promoting the E-cadherin accumulation at cell-cell junctions. Please cite this article as: Huang N, He HW, He YY, Gu W, Xu MJ, Liu L. Xiaotan Sanjie recipe, a compound Chinese herbal medicine, inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation. J Integr Med. 2023; 21(6): 561-574.

Vertically grown ultrathin Bi2SiO5 as high-κ single-crystalline gate dielectric.

Single-crystalline high-κ dielectric materials are desired for the development of future two-dimensional (2D) electronic devices. However, curent 2D gate insulators still face challenges, such as insufficient dielectric constant and difficult to obtain free-standing and transferrable ultrathin films. Here, we demonstrate that ultrathin Bi2SiO5 crystals grown by chemical vapor deposition (CVD) can serve as excellent gate dielectric layers for 2D semiconductors, showing a high dielectric constant (>30) and large band gap (~3.8 eV). Unlike other 2D insulators synthesized via in-plane CVD on substrates, vertically grown Bi2SiO5 can be easily transferred onto other substrates by polymer-free mechanical pressing, which greatly facilitates its ideal van der Waals integration with few-layer MoS2 as high-κ dielectrics and screening layers. The Bi2SiO5 gated MoS2 field-effect transistors exhibit an ignorable hysteresis (~3 mV) and low drain induced barrier lowering (~5 mV/V). Our work suggests vertically grown Bi2SiO5 nanoflakes as promising candidates to improve the performance of 2D electronic devices.

The Discovery of a High-Mobility Two-Dimensional Bismuth Oxyselenide Semiconductor and Its Application in Nonvolatile Neuromorphic Devices.

The development of two-dimensional (2D) electronics is always accompanied by the discovery of 2D semiconductors with high mobility and specific crystal structures, which may bring revolutionary breakthrough on proof-of-concept devices and physics. Here, Bi3O2.5Se2, a 2D bismuth oxyselenide semiconductor with non-neutral layered crystal structure is discovered. Ultrathin Bi3O2.5Se2 films are readily synthesized by chemical vapor deposition, displaying tunable band gaps and high room-temperature field-effect mobility of >220 cm2 V-1 s-1. Moreover, the as-synthesized Bi3O2.5Se2 nanoplates were fabricated into top-gated transistors with a simple device configuration, whose carrier density can be reversibly regulated in the range of 1014 cm-2 just by a facile method of electrostatic doping at room temperature. These features enable it to be functionalized into nonvolatile synaptic transistors with ultralow operating energy consumption (∼0.5 fJ), high repeatability, low operating voltage (0.1 V), and long retention time. Our work extends the family of bismuth oxyselenide 2D semicondutors.

Receptor for hyaluronan-mediated motility (RHAMM) defines an invasive niche associated with tumor progression and predicts poor outcomes in breast cancer patients.

Breast cancer invasion and metastasis result from a complex interplay between tumor cells and the tumor microenvironment (TME). Key oncogenic changes in the TME include aberrant synthesis, processing, and signaling of hyaluronan (HA). Hyaluronan-mediated motility receptor (RHAMM, CD168; HMMR) is an HA receptor enabling tumor cells to sense and respond to this aberrant TME during breast cancer progression. Previous studies have associated RHAMM expression with breast tumor progression; however, cause and effect mechanisms are incompletely established. Focused gene expression analysis of an internal breast cancer patient cohort confirmed that increased RHAMM expression correlates with aggressive clinicopathological features. To probe mechanisms, we developed a novel 27-gene RHAMM-related signature (RRS) by intersecting differentially expressed genes in lymph node (LN)-positive patient cases with the transcriptome of a RHAMM-dependent model of cell transformation, which we validated in an independent cohort. We demonstrate that the RRS predicts for poor survival and is enriched for cell cycle and TME-interaction pathways. Further analyses using CRISPR/Cas9-generated RHAMM-/- breast cancer cells provided direct evidence that RHAMM promotes invasion in vitro and in vivo. Immunohistochemistry studies highlighted heterogeneous RHAMM protein expression, and spatial transcriptomics associated the RRS with RHAMM-high microanatomic foci. We conclude that RHAMM upregulation leads to the formation of 'invasive niches', which are enriched in RRS-related pathways that drive invasion and could be targeted to limit invasive progression and improve patient outcomes. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Activated Carbon with Ultrahigh Specific Surface Derived from Bamboo Shoot Shell through K2FeO4 Oxidative Pyrolysis for Adsorption of Methylene Blue.

To effectively remove methylene blue (MB) from dye wastewater, a novel activated carbon (BAC) was manufactured through co-pyrolysis of bamboo shoot shell and K2FeO4. The activation process was optimized to a temperature of 750 °C and an activation time of 90 min based on its excellent adsorption capacity of 560.94 mg/g with a yield of 10.03%. The physicochemical and adsorption properties of BACs were investigated. The BAC had an ultrahigh specific surface area of 2327.7 cm2/g and abundant active functional groups. The adsorption mechanisms included chemisorption and physisorption. The Freundlich model could be used to describe the isothermal adsorption of MB. The kinetics confirmed that the adsorption of MB belonged to the pseudo-second-order model. Intra-particle diffusion was the main rate-limiting step. The thermodynamic study showed that the adsorption process was endothermic and temperature was beneficial for the improvement of adsorption property. Furthermore, the removal rate of MB was 63.5% after three cycles. The BAC will have great potential for commercial development for purifying dye wastewater.

Pyrolysis self-activation: An environmentally friendly method to transform biowaste into activated carbon for arsenic removal.

A green method for production of activated carbon and combustible gas was introduced. Without any external reagents and gases, the H2O and CO2 produced by the pyrolysis of bamboo shoot shells were used as activators. The prepared activated carbon had good arsenic adsorption properties with the maximum adsorption capacities of 10.9 mg/g for As(III) and 16.0 mg/g for As(V). The gaseous products were mostly CO and H2, with higher heating value of 11.7 MJ/Nm3. Thermogravimetric experiments were performed in N2, H2O and CO2 atmospheres to simulate the self-activation process and investigate the self-activation mechanism. This work will help to improve the competitiveness of self-activation technology and reduce the production cost of activated carbon.

High Mobility and Quantum Oscillations in Semiconducting Bi2O2Te Nanosheets Grown by Chemical Vapor Deposition.

Bi2O2Te has the smallest effective mass and preferable carrier mobility in the Bi2O2X (X = S, Se, Te) family. However, compared to the widely explored Bi2O2Se, the studies on Bi2O2Te are very rare, probably attributed to the lack of efficient ways to achieve the growth of ultrathin films. Herein, ultrathin Bi2O2Te crystals were successfully synthesized by a trace amount of O2-assisted chemical vapor deposition (CVD) method, enabling the observation of ultrahigh low-temperature Hall mobility of >20 000 cm2 V-1 s-1, pronounced Shubnikov-de Haas quantum oscillations, and small effective mass of ∼0.10 m0. Furthermore, few nm thick CVD-grown Bi2O2Te crystals showed high room-temperature Hall mobility (up to 500 cm2 V-1 s-1) both in nonencapsulated and top-gated device configurations and preserved the intrinsic semiconducting behavior with Ion/Ioff ∼ 103 at 300 K and >106 at 80 K. Our work uncovers the veil of semiconducting Bi2O2Te with high mobility and brings new blood into Bi2O2X family.

Molecular characterization of biphenotypic epithelioid and plexiform melanoma with deep penetrating nevus-like features.

Tumor heterogeneity is a relevant hallmark of melanoma due to the high mutation burden and immunogenicity commonly encountered. Heterogeneity at the histologic level frequently corresponds to heterogeneity at the molecular level. A better understanding of this feature of malignancy can help refine the development of predictive biomarkers and to define more effective targeted therapies. Here, we describe a case of melanoma displaying a dual phenotype: a DPN-like/plexiform portion in conjunction with a conventional epithelioid morphology. Molecular studies revealed shared BRAF and PTEN mutations in both components but a CTNNB1 mutation was exclusively found in the DPN-like area of the tumor, consistent with the distinct morphology observed. There was considerable heterogeneity in sequence variants identified in the two regions. Gene expression analysis highlighted differentially regulated genes between the two histologies, including a relevant cluster of genes in the receptor tyrosine kinase (RTK) family and related signaling pathways upregulated in the DPN-like/plexiform area.

Thermal Characteristics of Ash from Bamboo and Masson Pine Blends: Influence of Mixing Ratio and Heating Rate.

Thermal characteristics and kinetic parameters of ash from bamboo and masson pine blends with different mixing ratios were investigated using a thermogravimetric analyzer at different heating rates. The results showed that bamboo ash had lower fusion temperatures than the ash of masson pine. Mixing ratios and heating rates had a significant impact on the thermal characteristics and activation energy of ash samples. There was a synergistic interaction of chemical compositions in the bamboo and masson pine ashes. The mass loss of ash samples increased with the increase in the bamboo content of the blends. All ash samples had the maximum activation energy at the heating rate of 20 °C/min. The activation energy had a good linear correlation with mixing ratios at high conversion and heating rates. The optimum blend was suggested as 20% bamboo/80% masson pine due to its high activation energy. The results of this study are helpful to design a combustion system of bamboo and masson pine blends.

Characterization of the complete chloroplast genome of Melaleuca cajuputi subsp. cumingiana (Myrtaceae).

Plants in the genus Melaleuca have been widely used as traditional medicine mainly because of their broad spectrum antimicrobial activity. In this study, we reported the complete chloroplast genome of Melaleuca cajuputi subsp. cumingiana. The chloroplast genome of this species is 158,855 bp in length, including a pair of inverted repeat regions (IRs) (26,727 bp) that is divided by a large single-copy (LSC) area (87,338 bp) and a small single-copy (SSC) area (18,063 bp). The circular chloroplast genome of M. cajuputi subsp. cumingiana contains 135 unique genes, composing of 87 protein-coding genes, 40 tRNA genes, and eight rRNA genes. Phylogenetic analysis indicates that M. cajuputi subsp. cumingiana was clustered with species in the tribe Melaleuceae. This complete chloroplast genome of M. cajuputi subsp. cumingiana will provide a powerful tool to accelerate breeding, biotechnological and phylogenetic study.

Gene Expression and Mutational Profile in BAP-1 Inactivated Melanocytic Lesions of Progressive Malignancy from a Patient with Multiple Lesions.

BAP-1 (BRCA1-associated protein 1) inactivated melanocytic lesions are a group of familial or sporadic lesions with unique histology and molecular features. They are of great clinical interest, at least in part due to the potential for malignant transformation and association with a familial cancer predisposition syndrome. Here, we describe a patient with multiple spatially and temporally distinct melanocytic lesions with loss of BAP1 expression by immunohistochemistry. RNA sequencing was performed on three independent lesions spanning the morphologic spectrum: a benign nevus, an atypical tumor, and a melanoma arising from a pre-existing BAP1-inactivated nevus. The three lesions demonstrated largely distinct gene expression and mutational profiles. Gene expression analysis revealed that genes involved in receptor protein kinase pathways were progressively upregulated from nevus to melanoma. Moreover, a clear enrichment of genes regulated in response to UV radiation was found in the melanoma from this patient, as well as upregulation of MAPK pathway-related genes and several transcription factors related to melanomagenesis.

Epidermal growth factor receptor as a molecular determinant of glioblastoma response to dopamine receptor D2 inhibitors.

BACKGROUND: There are ongoing clinical trials exploring the efficacy of dopamine receptor D2 (DRD2) inhibition against glioblastomas, the most common primary brain tumor. Here we examine potential molecular determinants of this efficacy. METHODS: The Cancer Genome Atlas glioblastoma database and other published mRNA profiles were used to analyze the DRD2 and epidermal growth factor receptor (EGFR) expression pattern. In vitro and in vivo responses to DRD2 inhibitors were determined using patient-derived xenograft (PDX) glioblastoma models. Immunohistochemical studies were performed on clinically annotated glioblastoma samples derived from patients treated with ONC201. RESULTS: Analysis of clinical glioblastoma specimens derived from independent patient cohorts revealed an inverse correlation between EGFR and DRD2 mRNA expression, with implication that signaling mediated by these proteins shares overlapping functions. In independent panels of PDX glioblastoma lines, high EGFR expression was associated with poor in vitro and in vivo response to DRD2 inhibitors, including haloperidol and ONC201. Moreover, ectopic expression of a constitutively active EGFR, variant (v)III, suppressed glioblastoma sensitivity to ONC201. DRD2 expression positively correlated with expression of rate-limiting enzymes for dopamine synthesis as well as dopamine secretion, suggesting contribution of autocrine DRD2 signaling. Analysis of specimens from patients treated with ONC201 (n = 15) showed an inverse correlation between the intensity of EGFR staining and clinical response. The median overall survival for patients with high and low EGFR staining was 162 and 373 days, respectively (0.037). CONCLUSIONS: High EGFR expression is a determinant of poor glioblastoma response to DRD2. This finding should inform future clinical trial designs.

[Chiral order inorganic mesoporous silica used as stationary phase in gas chromatography].

Chiral mesoporous materials have widely applications in chiral separation, asymmetric catalysis, and chiral sensing. Chiral order inorganic mesoporous silica (COIMS) is a kind of chiral materials with high order mesoporous structure not containing organic component. Here we report that a COIMS diluted with a polysiloxane OV-1701 was explored as a novel stationary phase for capillary gas chromatography. The COIMS was synthesized from D-phenylalanine chiral source, and its separation properties of the chiral column were investigated. Eight enantiomers including chiral alcohols, dialcohols, esters and amino acid derivative have been resolved on the coated capillary column. In addition, COIMS chiral column also exhibits good selectivity for the separations of linear alkanes and alcohols. This work indicates that the column has the advantages of high temperature resistance and short analysis time, so it has great potential to develop it as a chiral stationary phase at high temperature.

A novel chiral inorganic mesoporous silica used as a stationary phase in GC.

Chiral mesoporous silica (CMS) has attracted widespread attention because of some unique properties, such as high surface area, uniformly structured nanoscale cavities, and excellent chemical and thermal stability. In this work, we report the utilization of a CMS as the stationary phase for the separation of racemates in gas chromatography (GC). A CMS-coated capillary column was fabricated by a dynamic coating method. Eighteen racemates belonging to different classes of organic compounds were separated on this column, including chiral alcohols, aldehydes, ketones, organic acids, halohydrocarbons, alkenes, alcohol amines, epoxides, and amino acid derivatives. In addition, linear alkanes, alcohols, and aromatic hydrocarbons have also been resolved.

Comparison of Frame-Based Versus Frameless Intracranial Stereotactic Biopsy: Systematic Review and Meta-Analysis.

BACKGROUND: Frame-based stereotaxy has generally been considered the reference standard for brain biopsies. However, frameless stereotaxy might expedite the efficiency of the clinical work flow. Conflicting findings have been reported regarding the relative efficacy and safety of frame-based and frameless needle biopsy of brain lesions. We performed a meta-analysis of the reported data to compare the relative efficacy, safety, and time efficiency of frame-based and frameless stereotactic needle biopsy. METHODS: The PubMed database was searched for studies comparing frame-based and frameless biopsy. Of the 5248 reports found, 15 were included in the present meta-analysis. RESULTS: The 15 studies included in the present meta-analysis included 2400 patients. Our analysis found no statistically significant differences between frame-based and frameless biopsy in the diagnostic yield (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.71-1.41), morbidity (OR, 1.13; 95% CI, 0.76-1.66), mortality (OR, 0.94; 95% CI, 0.40-2.17), postbiopsy hemorrhage (OR, 1.16; 95% CI, 0.68-1.96), and postbiopsy neurological deficit (OR, 1.01; 95% CI, 0.62-1.65). The results from our integrated analysis indicated that frameless biopsies are associated with a shorter procedural time relative to frame-based biopsy (standard difference in the mean, 0.64; 95% CI, 0.24-1.04; P = 0.002; I2 [Higgins inconsistency index] = 86.66%). CONCLUSIONS: The results from our meta-analysis suggest no significant differences exist between frame-based and frameless biopsy in diagnostic yield, morbidity, and mortality. Frameless biopsy is associated with shorter procedural times relative to frame-based biopsy. We have also discussed the relative merits of frame-based and frameless biopsies.