Coiling Variations for Treatment of Ruptured Intracranial Aneurysms: A Meta-Analytical Comparison of Comaneci-, Stent-, and Balloon-Coiling Assistance Techniques.

BACKGROUND: Wide-necked aneurysms represent a challenge for treatment in the setting of acute subarachnoid hemorrhage. Stent-assisted coiling (SAC) and balloon-assisted coiling (BAC) are well-known techniques for treating wide-necked aneurysms. Comaneci-assisted coiling (CAC) is a newer technique involving temporary stent deployment to assist aneurysm coiling. We aim to present the first meta-analysis comparing these treatments of ruptured aneurysms. METHODS: Following PRISMA guidelines, PubMed and Embase databases were queried from earliest records to July 2022 for literature reporting SAC, BAC, or CAC of ruptured intracranial aneurysms. A meta-analysis of identified articles was performed. RESULTS: Of the 571 articles queried, 64 articles were included. One study reported BAC and SAC, 8 reported BAC, 52 reported SAC, and 3 reported CAC. These studies comprised 3153 patients with 3207 ruptured aneurysms treated with CAC (161 patients and aneurysms), BAC (330 patients and aneurysms), and SAC (2662 patients, 2716 aneurysms). Rates of periprocedural thromboembolic or hemorrhagic complications, overall or procedure-related mortality, immediate complete occlusion, retreatment, and length of angiographic follow-up did not differ significantly between SAC and BAC. Periprocedural thromboembolic (P = 0.03) and hemorrhagic (P = 0.01) complication rates were higher with BAC than CAC. Periprocedural thromboembolic (P = 0.03) and hemorrhagic (P < 0.0001) complication rates were higher with SAC than CAC. Complete aneurysm occlusion rates (P = 0.033) were higher with CAC than BAC. No significant differences were present in CAC versus BAC or SAC retreatment rates. CONCLUSIONS: CAC was associated with lower hemorrhagic and thromboembolic complication rates and demonstrated similar complete occlusion and residual retreatment rates to those for BAC and SAC.

Implantable collamer lens implantation (ICL) versus small incision lenticule extraction (SMILE) in low to moderate myopia: study protocol for a randomized, non-inferiority trial.

BACKGROUND: Implantable collamer lens implantation (ICL) is a form of 'foldable' posterior chamber phakic intraocular lens refractive surgery that generally does not impair cornea and natural accommodation. The potential advantages of the ICL over keratorefractive laser procedures include less induction of higher-order aberrations (HOAs) and enhanced retinal image magnification. On the other hand, small incision lenticule extraction (SMILE), currently, one of the most popular refractive surgery procedures, also offers excellent visual outcomes, particularly for eyes with low to moderate amounts of myopia. The aim of this study is to evaluate whether ICL/TICL (toric ICL) is comparable to SMILE for low to moderate myopia in terms of refractive outcomes at 3 and 18 months post-operatively. METHODS/DESIGN: This is a prospective randomized study. A total of 300 participants will be randomized into two groups, the ICL/TICL group and SMILE group. Eligible participants with spherical equivalent (SE) less than - 6.0 diopter (D) will be recruited. Following randomization, participants will be followed at 1, 3, 6, 12, and 18 months. The primary outcome is the refractive predictability at every postoperative point after surgery, which is the proportion of the number of eyes achieving a postoperative SE within ± 0.5 D and ± 1.0 D of the intended target. Secondary outcome parameters include visual acuity, refraction, adverse events, and quality of vision measurements. DISCUSSION: This trial will provide information on whether ICL has comparable, if not superior, refractive outcomes compared to the established SMILE for low to moderate myopia, thus providing evidence for translation into clinical practice. TRIAL REGISTRATION: Chinese clinical trial registry (ChiCTR) 2200055372. Registered on 08 January 2022.

Rapid detection of SARS-CoV-2 RNA in saliva via Cas13.

Rapid nucleic acid testing is central to infectious disease surveillance. Here, we report an assay for rapid COVID-19 testing and its implementation in a prototype microfluidic device. The assay, which we named DISCoVER (for diagnostics with coronavirus enzymatic reporting), involves extraction-free sample lysis via shelf-stable and low-cost reagents, multiplexed isothermal RNA amplification followed by T7 transcription, and Cas13-mediated cleavage of a quenched fluorophore. The device consists of a single-use gravity-driven microfluidic cartridge inserted into a compact instrument for automated running of the assay and readout of fluorescence within 60 min. DISCoVER can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in saliva with a sensitivity of 40 copies µl-1, and was 94% sensitive and 100% specific when validated (against quantitative PCR) using total RNA extracted from 63 nasal-swab samples (33 SARS-CoV-2-positive, with cycle-threshold values of 13-35). The device correctly identified all tested clinical saliva samples (10 SARS-CoV-2-positive out of 13, with cycle-threshold values of 23-31). Rapid point-of-care nucleic acid testing may broaden the use of molecular diagnostics.

Accelerated RNA detection using tandem CRISPR nucleases.

Direct, amplification-free detection of RNA has the potential to transform molecular diagnostics by enabling simple on-site analysis of human or environmental samples. CRISPR-Cas nucleases offer programmable RNA-guided RNA recognition that triggers cleavage and release of a fluorescent reporter molecule, but long reaction times hamper their detection sensitivity and speed. Here, we show that unrelated CRISPR nucleases can be deployed in tandem to provide both direct RNA sensing and rapid signal generation, thus enabling robust detection of ~30 molecules per µl of RNA in 20 min. Combining RNA-guided Cas13 and Csm6 with a chemically stabilized activator creates a one-step assay that can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA extracted from respiratory swab samples with quantitative reverse transcriptase PCR (qRT-PCR)-derived cycle threshold (Ct) values up to 33, using a compact detector. This Fast Integrated Nuclease Detection In Tandem (FIND-IT) approach enables sensitive, direct RNA detection in a format that is amenable to point-of-care infection diagnosis as well as to a wide range of other diagnostic or research applications.

Accelerated RNA detection using tandem CRISPR nucleases.

Direct, amplification-free detection of RNA has the potential to transform molecular diagnostics by enabling simple on-site analysis of human or environmental samples. CRISPR-Cas nucleases offer programmable RNA-guided recognition of RNA that triggers cleavage and release of a fluorescent reporter molecule1,2, but long reaction times hamper sensitivity and speed when applied to point-of-care testing. Here we show that unrelated CRISPR nucleases can be deployed in tandem to provide both direct RNA sensing and rapid signal generation, thus enabling robust detection of ~30 RNA copies/microliter in 20 minutes. Combining RNA-guided Cas13 and Csm6 with a chemically stabilized activator creates a one-step assay that detected SARS-CoV-2 RNA from nasopharyngeal samples with PCR-derived Ct values up to 29 in microfluidic chips, using a compact imaging system. This Fast Integrated Nuclease Detection In Tandem (FIND-IT) approach enables direct RNA detection in a format amenable to point-of-care infection diagnosis, as well as to a wide range of other diagnostic or research applications.

Accelerated RNA detection using tandem CRISPR nucleases

Direct, amplification-free detection of RNA has the potential to transform molecular diagnostics by enabling simple on-site analysis of human or environmental samples. CRISPR-Cas nucleases offer programmable RNA-guided recognition of RNA that triggers cleavage and release of a fluorescent reporter molecule1,2, but long reaction times hamper sensitivity and speed when applied to point-of-care testing. Here we show that unrelated CRISPR nucleases can be deployed in tandem to provide both direct RNA sensing and rapid signal generation, thus enabling robust detection of [~]30 RNA copies/microliter in 20 minutes. Combining RNA-guided Cas13 and Csm6 with a chemically stabilized activator creates a one-step assay that detected SARS-CoV-2 RNA from nasopharyngeal samples with PCR-derived Ct values up to 29 in microfluidic chips, using a compact imaging system. This Fast Integrated Nuclease Detection In Tandem (FIND-IT) approach enables direct RNA detection in a format amenable to point-of-care infection diagnosis, as well as to a wide range of other diagnostic or research applications.

Liver damage favors the eliminations of HBV integration and clonal hepatocytes in chronic hepatitis B.

BACKGROUND: HBV integration is suspected to be an obstinate risk factor for hepatocellular carcinoma (HCC) in the era of antiviral therapy. Integration events start to occur in the immunotolerance phase, but their fates in the immune clearance phase have not yet been clarified. Here, we report the influences of liver damage on HBV integration and clonal hepatocyte expansion in patients with chronic hepatitis B (CHB). METHODS: HBV integration breakpoints in liver biopsy samples from 54 CHB patients were detected using a modified next-generation sequencing assay. RESULTS: A total of 3729 (69 per sample) integration breakpoints were found in the human genome, including some hotspot genes and KEGG pathways, especially in patients with abnormal transaminases. The number of breakpoint types, an integration risk parameter, was negatively correlated with HBV DNA load and transaminase levels. The average, maximum and total frequencies of given breakpoint types, parameters of clonal hepatocyte expansion, were negatively correlated with HBV DNA load, transaminase levels and liver inflammation activity grade score. The HBV DNA load and inflammation activity grade score were further found to be positively correlated with transaminase levels. Moreover, nucleos(t)ide analog (NUC) treatment that normalized transaminases nonsignificantly reduced the types, but significantly increased the average frequency and negated the enrichments of integration breakpoints. CONCLUSION: Liver damage mainly removed the inventories of viral integration and clonal hepatocytes in CHB. NUC treatment may have reduced HBV integration but clearly increased clonal hepatocyte expansion, which may explain why HCC risk cannot be ruled out by NUC treatment.

Rapid, point-of-care molecular diagnostics with Cas13.

Rapid nucleic acid testing is a critical component of a robust infrastructure for increased disease surveillance. Here, we report a microfluidic platform for point-of-care, CRISPR-based molecular diagnostics. We first developed a nucleic acid test which pairs distinct mechanisms of DNA and RNA amplification optimized for high sensitivity and rapid kinetics, linked to Cas13 detection for specificity. We combined this workflow with an extraction-free sample lysis protocol using shelf-stable reagents that are widely available at low cost, and a multiplexed human gene control for calling negative test results. As a proof-of-concept, we demonstrate sensitivity down to 40 copies/µL of SARS-CoV-2 in unextracted saliva within 35 minutes, and validated the test on total RNA extracted from patient nasal swabs with a range of qPCR Ct values from 13-35. To enable sample-to-answer testing, we integrated this diagnostic reaction with a single-use, gravity-driven microfluidic cartridge followed by real-time fluorescent detection in a compact companion instrument. We envision this approach for Diagnostics with Coronavirus Enzymatic Reporting (DISCoVER) will incentivize frequent, fast, and easy testing.

[Quality evaluation of Gastrodiae Rhizoma standard decoction based on UPLC fingerprint and quantitative analysis multi-components method].

To establish the quantitative analysis multi-components with a single-marker(QAMS) method for six components and fingerprint of standard decoction of Gastrodiae Rhizoma, verify the accuracy and feasibility of the method, and evaluate the quality of standard decoction. Based on UPLC with gastrodin as the internal standard, relative correction factors of p-hydroxybenzyl alcohol, parishin E, parishin B, parishin C, parishin A and gastrodin were determined by investigating the column temperature, flow rate, chromatographic columns and multi-point concentration correction. The total contents in 18 batches of standard decoction of Gastrodiae Rhizoma and the similarity were determined to calculate the similarity. The results of standard curve method, external standard one-point method and quantitative analysis multi-components with a single-marker(QAMS) were compared, and the results showed that there was no significant difference among these three methods. By analyzing the results of standard decoctions from different origins, it can be seen that the quality of Gastrodia standard decoctions derived from Anhui and Yunnan was better, followed by Shaanxi and Hubei, and relatively poor in Gansu, with similarities all above 0.90 in the fingerprints. Therefore, the QAMS method that can measure the contents of gastrodin, p-hydroxybenzyl alcohol, parishin E, parishin B, parishin C and parishin A in standard decoction of Gastrodiae Rhizoma combined with fingerprint is accurate, feasible and fast, which can be used to evaluate the quality of standard decoction of Gastrodiae Rhizoma, and also provide a reference for the research on the quality standards of raw materials for Gastrodiae Rhizoma prepared slices and alike.

Rapid detection of SARS-CoV-2 with Cas13

Rapid nucleic acid testing is a critical component of a robust infrastructure for increased disease surveillance. Here, we report a microfluidic platform for point-of-care, CRISPR-based molecular diagnostics. We first developed a nucleic acid test which pairs distinct mechanisms of DNA and RNA amplification optimized for high sensitivity and rapid kinetics, linked to Cas13 detection for specificity. We combined this workflow with an extraction-free sample lysis protocol using shelf-stable reagents that are widely available at low cost, and a multiplexed human gene control for calling negative test results. As a proof-of-concept, we demonstrate sensitivity down to 40 copies/L of SARS-CoV-2 in unextracted saliva within 35 minutes, and validated the test on total RNA extracted from patient nasal swabs with a range of qPCR Ct values from 13-35. To enable sample-to-answer testing, we integrated this diagnostic reaction with a single-use, gravity-driven microfluidic cartridge followed by real-time fluorescent detection in a compact companion instrument. We envision this approach for Diagnostics with Coronavirus Enzymatic Reporting (DISCoVER) will incentivize frequent, fast, and easy testing.

Visual outcomes and corneal biomechanics after V4c implantable collamer lens implantation in subclinical keratoconus.

PURPOSE: To quantitatively evaluate the safety, efficacy, stability, predictability, and corneal biomechanical parameters after V4c implantable collamer lens (ICL) implantation in subclinical keratoconus. SETTING: Xi'an AIER Eye Hospital, Xi'an, China. DESIGN: Retrospective case series. METHODS: Patients undergoing V4c ICL/toric ICL implantation were examined. Scheimpflug tomography (Pentacam) was used to measure the Belin-Ambrosio enhanced ectasia total deviation index. Dynamic Scheimpflug biomechanical analysis (CorVis ST) was used to measure the corneal biomechanical parameters and Corvis Biomechanical Index. The Tomographic and Biomechanical Index was measured by combined Pentacam with CorVis ST. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction, and adverse effects were also investigated. RESULTS: A total of 60 eyes of 60 patients (mean age ± SD, 27.21 ± 7.24 years) were included. The mean preoperative UDVA and CDVA were 1.08 ± 0.25 and 0.12 ± 0.04 logarithm of the minimum angle of resolution (logMAR) (20/230 and 20/28 Snellen VA), respectively. After 2 years, the mean postoperative UDVA and CDVA were 0.01 ± 0.06 and -0.05 ± 0.03 logMAR (20/20 and 20/18 Snellen VA), respectively. The mean difference between the intended and achieved spherical equivalent (SE) was -0.08 ± 0.47 diopter (D), and the SE was within ±1.00 D of the intended correction in 57 eyes (95%), and 58 eyes (97%) had astigmatism less than 0.50 D. The refractive results were stable 2 years postoperatively, and the corneal biomechanical parameters returned to their preoperative levels at 3 months. CONCLUSIONS: The V4c ICL/toric ICL in subclinical keratoconus offered predictable correction of SE refractive error. Refractive results and corneal biomechanics were stable at the 2-year follow-up.

Autophagy in intracellular bacterial infection.

Autophagy is a conserved intracellular degradation process enclosing the bulk of cytosolic components for lysosomal degradation to maintain cellular homeostasis. Accumulating evidences showed that a specialized form of autophagy, known as xenophagy, could serve as an innate immune response to defend against pathogens invading inside the host cells. Correspondingly, infectious pathogens have developed a variety of strategies to disarm xenophagy, leading to a prolonged and persistent intracellular colonization. In this review, we first summarize the current knowledge about the general mechanisms of intracellular bacterial infections and xenophagy. We then focus on the ongoing battle between these two processes.

The Virus Bioresistor: Wiring Virus Particles for the Direct, Label-Free Detection of Target Proteins.

The virus bioresistor (VBR) is a chemiresistor that directly transfers information from virus particles to an electrical circuit. Specifically, the VBR enables the label-free detection of a target protein that is recognized and bound by filamentous M13 virus particles, each with dimensions of 6 nm ( w) × 1 µm ( l), entrained in an ultrathin (∼250 nm) composite virus-polymer resistor. Signal produced by the specific binding of virus to target molecules is monitored using the electrical impedance of the VBR: The VBR presents a complex impedance that is modeled by an equivalent circuit containing just three circuit elements: a solution resistance ( Rsoln), a channel resistance ( RVBR), and an interfacial capacitance ( CVBR). The value of RVBR, measured across 5 orders of magnitude in frequency, is increased by the specific recognition and binding of a target protein to the virus particles in the resistor, producing a signal Δ RVBR. The VBR concept is demonstrated using a model system in which human serum albumin (HSA, 66 kDa) is detected in a phosphate buffer solution. The VBR cleanly discriminates between a change in the electrical resistance of the buffer, measured by Rsoln, and selective binding of HSA to virus particles, measured by RVBR. The Δ RVBR induced by HSA binding is as high as 200 Ω, contributing to low sensor-to-sensor coefficients-of-variation (<15%) across the entire calibration curve for HSA from 7.5 nM to 900 nM. The response time for the VBR is 3-30 s.

Reduced lysosomal clearance of autophagosomes promotes survival and colonization of Helicobacter pylori.

Evasion of autophagy is key for intracellular survival of bacteria in host cells, but its involvement in persistent infection by Helicobacter pylori, a bacterium identified to invade gastric epithelial cells, remains obscure. The aim of this study was to functionally characterize the role of autophagy in H. pylori infection. Autophagy was assayed in H. pylori-infected human gastric epithelium and the functional role of autophagy was determined via genetic or pharmacological ablation of autophagy in mouse and cell line models of H. pylori infection. Here, we showed that H. pylori inhibited lysosomal function and thereby promoted the accumulation of autophagosomes in gastric epithelial cells. Importantly, inhibiting autophagosome formation by pharmacological inhibitors or genetic ablation of BECN1 or ATG5 reduced H. pylori intracellular survival, whereas inhibition of lysosomal functions exerted an opposite effect. Further experiments demonstrated that H. pylori inhibited lysosomal acidification and the retrograde trafficking of mannose-6-phosphate receptors, both of which are known to positively regulate lysosomal function. We conclude that H. pylori subverts autophagy into a pro-survival mechanism through inhibition of lysosomal clearance of autophagosomes. Disruption of autophagosome formation offers a novel strategy to reduce H. pylori colonization in human stomachs. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The Historical Progression From ADL Scrutiny to IADL to Advanced ADL: Assessing Functional Status in the Earliest Stages of Dementia.

Background: Decrements in instrumental activities (IADL) have been observed in the prodromal phase of dementia. Given the long predementia stage in neurodegenerative diseases, it has been proposed that subtle functional changes may precede clinical IADL impairment. Incorporating more challenging advanced ADLs (eg, volunteer work) into the assessment process may increase the sensitivity of functional measures, thus expanding the window for monitoring or interventions. Methods: Longitudinal cohort study was used (follow-ups, 18-24 month), with subjects aged 60 and older (n = 3,635). To elucidate the relationship between cognitive ability and functional status we employed an IADL scale with an extended range (ADL-extended; includes IADL but also more challenging advanced ADLs) that meets item response theory properties of dimensionality, monotonicity, and item hierarchy. Procedures involved (a) a dynamic change model employed to inspect the temporal relationship between ADL-extended and cognitive status and (b) Cox proportional hazards to assess the risk of incident dementia based on ADL-extended scores. Results: Growth curve modeling: baseline ADL-extended was significantly associated with all four cognitive domains investigated. Worse baseline ADL-extended was associated with more rapid declines in speed/executive function, and worse baseline memory was associated with more rapid declines in ADL-extended; a concurrent association was found for language and ADL-extended. Cox model: the risk of dementia was decreased for each additional ADL-extended item endorsed (hazard ratio [HR], 0.85; 95% confidence interval = 0.81-0.90). Conclusions: An increased risk of dementia could be observed in the ADL-extended items, which reflects an area of the functional continuum beyond IADL competencies.

Payload hardware and experimental protocol development to enable future testing of the effect of space microgravity on the resistance to gentamicin of uropathogenic Escherichia coli and its σs-deficient mutant.

Human immune response is compromised and bacteria can become more antibiotic resistant in space microgravity (MG). We report that under low-shear modeled microgravity (LSMMG), stationary-phase uropathogenic Escherichia coli (UPEC) become more resistant to gentamicin (Gm), and that this increase is dependent on the presence of σs (a transcription regulator encoded by the rpoS gene). UPEC causes urinary tract infections (UTIs), reported to afflict astronauts; Gm is a standard treatment, so these findings could impact astronaut health. Because LSMMG findings can differ from MG, we report preparations to examine UPEC's Gm sensitivity during spaceflight using the E. coli Anti-Microbial Satellite (EcAMSat) as a free-flying "nanosatellite" in low Earth orbit. Within EcAMSat's payload, a 48-microwell fluidic card contains and supports study of bacterial cultures at constant temperature; optical absorbance changes in cell suspensions are made at three wavelengths for each microwell and a fluid-delivery system provides growth medium and predefined Gm concentrations. Performance characterization is reported here for spaceflight prototypes of this payload system. Using conventional microtiter plates, we show that Alamar Blue (AB) absorbance changes can assess the Gm effect on E. coli viability, permitting telemetric transfer of the spaceflight data to Earth. Laboratory results using payload prototypes are consistent with wellplate and flask findings of differential sensitivity of UPEC and its ∆rpoS strain to Gm. if σs plays the same role in space MG as in LSMMG and Earth gravity, countermeasures discovered in recent Earth studies (aimed at weakening the UPEC antioxidant defense) to control UPEC infections would prove useful also in space flights. Further, EcAMSat results should clarify inconsistencies from previous space experiments on bacterial antibiotic sensitivity and other issues.

Corneal Nerve Regeneration after Self-Retained Cryopreserved Amniotic Membrane in Dry Eye Disease.

PURPOSE: To evaluate the efficacy of self-retained cryopreserved amniotic membrane (CAM) in promoting corneal nerve regeneration and improving corneal sensitivity in dry eye disease (DED). METHODS: In this prospective randomized clinical trial, subjects with DED were randomized to receive CAM (study group) or conventional maximum treatment (control). Changes in signs and symptoms, corneal sensitivity, topography, and in vivo confocal microscopy (IVCM) were evaluated at baseline, 1 month, and 3 months. RESULTS: Twenty subjects (age 66.9 ± 8.9) were enrolled and 17 completed all follow-up visits. Signs and symptoms were significantly improved in the study group yet remained constant in the control. IVCM showed a significant increase in corneal nerve density in the study group (12,241 ± 5083 µm/mm2 at baseline, 16,364 ± 3734 µm/mm2 at 1 month, and 18,827 ± 5453 µm/mm2 at 3 months, p = 0.015) but was unchanged in the control. This improvement was accompanied with a significant increase in corneal sensitivity (3.25 ± 0.6 cm at baseline, 5.2 ± 0.5 cm at 1 month, and 5.6 ± 0.4 cm at 3 months, p < 0.001) and corneal topography only in the study group. CONCLUSIONS: Self-retained CAM is a promising therapy for corneal nerve regeneration and accelerated recovery of the ocular surface health in patients with DED. The study is registered at clinicaltrials.gov with trial identifier: NCT02764814.

Glucose-regulated protein 78 demonstrates antiviral effects but is more suitable for hepatocellular carcinoma prevention in hepatitis B.

BACKGROUND: Hepatitis B virus (HBV) is the leading cause of liver cirrhosis and hepatocellular carcinoma in Asia and Africa. Existing antivirals cannot cure HBV or eliminate risk of hepatocellular carcinoma. Glucose-regulated protein 78 (GRP78) can inhibit HBV replication, but promote virion secretion and hepatocellular cancer cell invasion. For these reasons, the overall effect of GRP78 on HBV production and whether to utilize the HBV replication-inhibitory effect of GRP78 up-regulation or the hepatocellular cancer cell invasion-inhibitory effect of its down-regulation were further investigated in order to improve the efficacy of current antiviral therapy. METHODS: GRP78 regulations in HepG2.2.15 cells were conducted by transfections of expressing vector and small interfering RNA, respectively. The changes in HBV replication, hepatitis B e antigen (HBeAg) synthesis and hepatoma cell motility were monitored. RESULTS: GRP78 overall decreased HBV production due to its HBV replication-inhibitory effect time-dependently overwhelming virion secretion-promoting effect in HepG2.2.15 cells. Unlike the parental cells (HepG2), HepG2.2.15 cells demonstrated decreased expressions of the major genes in the interferon-ß1-dependent pathway. Moreover, the expressions of these genes were not affected by GRP78 regulations. However, GRP78 was found to inhibit HBeAg secretion and to increase the retro-transportation of capsid assembly-interfering HBeAg precursor from the endoplasmic reticulum into the cytosol where new viral nucleocapsids formed. Furthermore, GRP78 overexpression promoted wound healing process (the motility) of HepG2.2.15 cells. In contrast, GRP78 knockdown enhanced HBV replication and HBeAg secretion, but they were abolished by entecavir and furin inhibitor, respectively. CONCLUSIONS: GRP78 mainly demonstrates anti-HBV effects, reducing HBV production and HBeAg secretion. With due regard to the hepatocellular cancer invasion risk of the overexpression and the rectifiability of the unpleasant effects of the knockdown, GRP78 down-regulation may be more suitable to serve as an additive strategy to cover the hepatocellular cancer prevention shortage of current antiviral therapy in the future.