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A proximity effect facilitates the penetration of Cooper pairs that permits superconductivity in a normal metal, offering a promising approach to turn heterogeneous materials into superconductors and develop exceptional quantum phenomena. Here, we have systematically investigated proximity-induced anisotropic superconductivity in a monolayer Ni-Pb binary alloy by combining scanning tunneling microscopy/spectroscopy (STM/STS) with theoretical calculations. By means of high-temperature growth, the ( 3 3 × 3 3 ) R 30 o Ni-Pb surface alloy has been fabricated on Pb(111) and the appearance of a domain boundary as well as a structural phase transition can be deduced from a half-unit-cell lattice displacement. Given the high spatial and energy resolution, tunneling conductance (d I /d U ) spectra have resolved the reduced but anisotropic superconducting gap Δ NiPb ≈ 1.0 meV, in stark contrast to the isotropic Δ Pb ≈ 1.3 meV. In addition, the higher density of states at the Fermi energy ( D ( E F )) of the Ni-Pb surface alloy results in an enhancement of coherence peak height. According to the same T c ≈ 7.1 K with Pb(111) from the temperature-dependent Δ NiPb and the short decay length L d ≈ 3.55 nm from the spatially monotonic decrease of Δ NiPb , both results are supportive of a proximity-induced superconductivity. Despite a lack of a bulk counterpart, the atomically thick Ni-Pb bimetallic compound opens a pathway to engineer superconducting properties down to the two-dimensional limit, giving rise to the emergence of anisotropic superconductivity via a proximity effect.

Background: Anti-GQ1b antibody syndrome referred to a clinical spectrum characterized by acute onset of ataxia, ophthalmoplegia and areflexia, while visual deterioration was rarely reported in terms of ocular disorders. This study aimed to describe the clinical characteristics of anti-GQ1b antibody syndrome with visual impairment., Methods: The database at the First Affiliated Hospital of Sun Yat-sen University was searched from 2014 to 2020. Patients with anti-GQ1b IgG were identified and divided into two groups according to the existence of optic neuropathy. Clinical and laboratory data of these subjects between the two groups were collected and analyzed. All patients were followed up by telephone to assess the outcome., Results: A total of 12 patients with seropositive anti-GQ1b antibody were included, 75% of which got antecedent infection. Of these cases, 3 showed visual deterioration accompanied by abnormal orbital magnetic resonance imaging or visual evoked potentials, and the other 9 didn't show any evidence of vision impairment. Patients in the optic neuropathy group presented prominent visual impairments as initial symptoms and were more likely to suffer from facial weakness. There were 4 patients in normal visual acuity group complaining of blurred vision due to intraocular muscle paralysis, which was distinguished by subsequent examination. The combination of glucocorticoids and intravenous immunoglobulin was applied to treat patients with optic neuropathy., Conclusions: This study provides strong evidence that anti-GQ1b antibody syndrome can exhibit visual impairment, which helps further expand the clinical spectrum of anti-GQ1b antibody syndrome. More attention should be paid to the physical and supplementary ophthalmological examination to explore the pathogenesis and treatment of anti-GQ1b antibody syndrome., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Purpose: To investigate the accuracy of 6 intraocular lens (IOL) power calculation formulas in predicting refractive outcomes in extremely long eyes., Setting: Department of Ophthalmology, Far Eastern Memorial Hospital, Taiwan., Design: Retrospective comparative study., Methods: In this retrospective single-center study, we reviewed 70 eyes of 70 patients with axial length (AL) ≥ 28 mm who had received an uneventful 2.2 mm corneal wound phacoemulsification and in-the-bag IOL placement. The actual postoperative refractive results were compared to the predicted refraction calculated with 6 formulas (Haigis, Hoffer Q, Holladay 1, SRK/T, T2, Barrett Universal II formulas) using IOLMaster 500 as optical biometry in the User Group for Laser Interference Biometry (ULIB) constants., Results: Overall, the Haigis and Barrett formulas achieved the lowest level of mean prediction error (PE) and median absolute error (MedAE). Hoffer Q, Holladay 1, SRK/T, and T2 had hyperopic prediction errors ( p < 0.05). The Hoffer Q and Holladay 1 had significantly more MedAE between the 6 formulas. After the mean PE was zeroed out, the MedAE had no significant difference between each group. The absolute error tends to be larger in patients with longer AL. The absolute errors were 30.0-37.1% and 60.0-64.3% within 1.0 D of all patients compared to predicted refraction calculated using various formulas., Conclusion: The Haigis and Barrett Universal II formulas had a better success rate in predicting IOL power in high myopic eyes with AL longer than 28 mm using the ULIB constant in this study. The postoperative refractive results were inferior to the benchmark standards, which indicated that the precision of IOL power calculation in patients with high myopia still required improvement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chu, Huang, Chang, Ho, Hsu, Chang and Wang.)

In this report, 19 boron-containing depsipeptides were synthesized via microwave-assisted Passerini three-component reaction (P-3CR) in an aqueous environment. The linker-free DAHMI fluorescent tagging approach was used on selected boron-containing compounds to study the relationship between their structures and their level of cellular uptake of HEK293 cells. The biological data retrieved from the DAHMI experiments indicated that while the structures of tested compounds may be highly similar, their bio-distribution profile could be vastly distinctive. The reported optimized one-pot synthetic strategy along the linker-free in vitro testing protocol could provide an efficient platform to accelerate the development of boron-containing drugs.

Background: Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are one of the most common outpatient bacterial infections. Although bacterial and host factors are reported to be associated with UTI pathogenesis, little is known about the host age-related differences in bacterial virulence factors and antimicrobial susceptibility., Methods: PCRs were carried out to detect K1 capsule antigen, 15 virulence factors, and phylogenetic groups in E. coli isolates. Antimicrobial susceptibility of selected agents was determined by the disk diffusion method. Isolates were divided into 6 groups based on their host age., Results: The results showed that virulence factors PapGII, PapGIII, Cnf1, Aer, Usp, Iha, OmpT, HlyA, and Sat, had highest frequencies in the host age group 0-3. Phylogenetic group B2 dominated in our isolates (59.6%) followed by group D (20.7%). In addition, 77.4% of strains isolated from 0 to 3 age group belonged to phylogenetic group B2. Antimicrobial susceptibility tests showed that E. coli strains isolated were significantly more resistant to antimicrobial agents as host age increased. Phylogenetic group B2 isolates were more susceptible to antimicrobial agents, compared to A, B1, and D isolates., Conclusion: We found E. coli isolated from elders were more resistant to antimicrobial agents and had less virulence factors., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

We examined the barrier effects against Bemisia tabaci and the potential to control the tomato yellow leaf curl virus (TYLCV) of different tomato-maize intercropping modes. Tomatoes (variety Jinshan 511) were planted at a fixed row distance either as a monoculture or together with maize (variety Xianyu 335) at the distances of 10, 20, and 30 cm. We investigated the viral index for TYLCV and the population density of B. tabaci . Compared with tomato monoculture, the natural barrier established by the maize stabilized the growth environment for tomato. When the maize spacing was 10, 20, and 30 cm, the average temperature of tomato plants from 6:00 to 20:00 decreased by 3.01, 2.26, and 1.45 ℃, the average relative humidity increased by 13.0%, 8.8%, and 6.0%, and the mean light intensity reduced by 26.1%, 20.4%, and 14.5%, respectively. The changes of those factors alleviated the adverse environmental conditions ( i.e ., intense light, high temperature, and lack of moisture) that promote the spread of virus-related diseases during the high-temperature period of the day, with the most effective planting distance for the maize being 10 cm. Our results suggested that the intercropping of tomato and maize had a barrier effect against B. tabaci and was able to control the TYLCV in tomato. When the planting distance for the maize was 10, 20, and 30 cm, the number of B. tabaci was 88.7%, 82.0%, and 73.9% lower than tomato monoculture, respectively. The TYLCV was inhibited, with the viral disease index being decreased by 67.3%, 59.4%, and 44.5%, respectively. Tomato-maize intercropping was also beneficial for tomato plant growth and fruit set, which could enhance tomato yield. Such effect was strengthened under higher maize density.

Background: Monomicrobial necrotizing fasciitis caused by Vibrio vulnificus , Aeromonas hydrophila , and Aeromonas sobria are often associated with high mortality rates. The purpose of this study was to compare the independent predictors related to outcomes between Vibrio vulnificus and Aeromonas species necrotizing fasciitis. Patients and Methods: Monomicrobial necrotizing fasciitis caused by Vibrio vulnificus (60 patients) and Aeromonas species (31 patients) over an 11-year period were reviewed retrospectively. Differences in mortality, patient characteristics, clinical presentations, and laboratory data were compared between the Vibrio vulnificus and Aeromonas species groups, and between the death and the survival subgroups of patients with Aeromonas species. Results: Six patients in the Vibrio vulnificus group (10%) and 11 in the Aeromonas species group (32.3%) died. Fifty-nine patents had bacteremia and 16 patients died (27.1%). Patients who had Vibrio vulnificus had a higher incidence of bacteremia. The patients who had Aeromonas species presenting with bacteremia were significantly associated with death. The death subgroup of patients with Aeromonas necrotizing fasciitis had a higher incidence of bacteremia, higher counts of banded leukocytes, lower platelet counts, lower total lymphocyte counts, and lower serum albumin level than the survival subgroup. Conclusions: Monomicrobial necrotizing fasciitis caused by Aeromonas species was characterized by more fulminating and higher mortality than that of Vibrio vulnificus , even after early fasciotomy and third-generation cephalosporin antibiotic therapy. Those risk factors, such as bacteremia, shock, lower platelet counts, lower albumin levels, and antibiotic resistance were associated with mortality, which should alert clinicians to pay more attention to and aggressively treat those patients with Aeromonas and Vibrio necrotizing fasciitis.

Background: To identify the correlation among female age, cellular aging markers, and aneuploidy rate in in vitro fertilization (IVF) and the preimplantation genetic test for aneuploidy (PGT-A) cycles. Methods: This is a prospective cohort study recruiting 110 infertile women between August 2017 and July 2018. They were divided into young-age (<38 years, n = 60) and advanced-age (≥38 years, n = 50) groups. Peripheral leukocytes were assessed, and the granulosa cells were pooled during oocyte pickup. Mitochondrial DNA (mtDNA) copy number and telomere length (TL) were measured using real-time polymerase chain reaction. PGT-A was performed on the NGS platform. Results: mtDNA copy number and TL were positively correlated in both leukocytes (rho = 0.477, p < 0.001) and granulosa cells (rho = 0.361, p < 0.001), but the two parameters in leukocytes were not correlated with those in granulosa cells. In the young-age group, TL in the granulosa cells was the only factor correlated with the aneuploidy rate (rho = −0.283, p = 0.044), whereas in the advanced-age group, age was the main factor (rho = 0.358, p = 0.018). Conclusions: TL in the granulosa cells was negatively correlated with the aneuploidy rate in the young-age group, supporting the application of PGT-A in younger women.

Objective: To investigate the protective effect of edaravone on chlorpyrifos-induced neuronal apoptosis and its mitochondrial mechanism. Methods: Under the principle of randomization and double-blindness, the rats were divided into control group, chlorpyrifos group, and edaravone group ( n =6). The rats in edaravone group were treated with edaravone (10 mg/1.6 ml/kg, ip.) 1 h after chlorpyrifos injection. After continuous injection of chlorpyrifos and edaravone for 28 days, the learning and memory abilities of the rats were tested by open field and water maze tests. The rat brain tissue was collected after cardiac perfusion, and the neuronal damage in the hippocampus of the brain was detected by HE staining and the mitochondrial and nuclear damage were observed by transmission electron microscopy. The contents of Na + -K + -ATPase and ATP were measured to evaluate mitochondrial damage. The expression of mitochondrial fission protein DRP1 and phosphorylation at Ser 637 of DRP1 were determined by immunohistochemistry and immunoblotting. Results: Compared with the control group, the total movement distance and average speed of the rats in the chlorpyrifos group were decreased significantly within 3 minutes of the open field test ( P ＜0.01), and the escape latency within 1 minute of the water maze test was prolonged significantly. The number of platform crossings was reduced significantly ( P ＜0.01), the activity of ATPase in brain tissue was decreased significantly ( P ＜0.01) , the content of ATP and the phosphorylation level of Ser637 of mitochondrial DRP1 were decreased significantly ( P ＜0.05, P ＜0.01). After edaravone treatment, the total movement distance and average speed of rats in the open field test were increased ( P ＜0.05), the latency in the water maze test was decreased, and the number of crossing platforms was increased ( P ＜0.01), brain pathological sections showed that nerve cells were arranged neatly, nucleus and mitochondrial damage was significantly improved, the activity of ATPase in brain tissue was increased ( P ＜0.01), the levels of ATP and mitochondrial DRP1 Ser637 phosphorylation increased ( P ＜0.05, P ＜0.01). Conclusion: Edaravone alleviates chlorpyrifos-induced brain injury in rats by promoting the phosphorylation of DRP1 at Ser637.

Background and Aims: The itemization difference of patient-reported outcome (PRO) in hepatitis patients with different etiologies remains elusive in Asia. We aimed to assess the characteristics and the difference of health-related quality of life (HRQoL) in chronic hepatitis B (CHB), chronic hepatitis C (CHC), and non-alcoholic fatty liver disease (NAFLD) patients., Methods: We conducted the study in an outpatient setting. The 36-Item Short Form Health Survey (SF-36) was completed by the patients upon the initial diagnosis and recruitment for a long-term follow-up purpose. The PRO results were also assessed by disease severity., Results: There were 244 patients (198 males) of CHB, 54 patients (29 males) of CHC, and 129 patients (85 males) of NAFLD, respectively. CHC patient had the mean score of 67.1 ± 23.3 in physical component summary (PCS) of the SF-36 health survey, which was significantly lower than CHB patients (76.4 ± 19.5), and NAFLD patients (77.5 ± 13.7), respectively (p = 0.001). The significantly lower performance of PCS in CHC patients was mainly attributed to the lower performance in physical functioning and bodily pain components. Higher fibrosis 4 index scores were significantly associated with lower PCS scores in all patient groups. There was no significant difference of mean mental component summary (MCS) between groups. However, NAFLD patients had significantly lower mental health scores than other groups (p = 0.02)., Conclusions: The significant difference of HRQoL exists in hepatitis patients with different etiologies. Disease severity leads to a lower PCS performance., Competing Interests: The authors have declared that no competing interests exist.

CCCTC-binding factor (CTCF) is critical to three-dimensional genome organization. Upon differentiation, CTCF insulates active and repressed genes within Hox gene clusters. We conducted a genome-wide CRISPR knockout (KO) screen to identify genes required for CTCF-boundary activity at the HoxA cluster, complemented by biochemical approaches. Among the candidates, we identified Myc-associated zinc-finger protein (MAZ) as a cofactor in CTCF insulation. MAZ colocalizes with CTCF at chromatin borders and, similar to CTCF, interacts with the cohesin subunit RAD21. MAZ KO disrupts gene expression and local contacts within topologically associating domains. Similar to CTCF motif deletions, MAZ motif deletions lead to derepression of posterior Hox genes immediately after CTCF boundaries upon differentiation, giving rise to homeotic transformations in mouse. Thus, MAZ is a factor contributing to appropriate insulation, gene expression and genomic architecture during development., (© 2022. The Author(s).)

Background: The presence of only morphologically poor embryos (MPEs) on day3 is common in autologous in vitro fertilization (IVF), particularly among p Tel: 886-7-7317123 Ext. 8916. Fax: 886-7-7322915.atients who have advanced maternal age or are poor responders. However, there are limited data regarding the disposition of embryos from patients who only produced MPEs on day3. The present study was designed to investigate the possible benefits of extended culturing MPEs. Try to detect whether the extended culture (day4 or day5 culture) can improve the live birth rate per cycle?, Methods: This retrospective, observational, single-center, cohort study examined 224 IVF/intracytoplasmic sperm injection (ICSI) cycles between January 2010 and June 2015, in which women only produced MPEs on day3. A total of 544 MPEs were analyzed. The defines a day3 embryo as an MPE if it fails to develop to eight cells, blastomeres of equal size, and less than 20% cytoplasmic fragments. Of the 224 cycles, 89 (39.7%) underwent fresh embryo transfer on day3, and 135 (60.3%) underwent extended culture. Of the 135 extended cultures, 54 cycles (40.0%) experienced day4, or day5 embryo transfer, 16 cycles (11.9%) had all embryos frozen, and 65 cycles (48.1%) had total embryo arrest., Results: Analysis of patient baseline demographic data, cycle characteristics, and cycle outcomes for day3 transfer group and extended culture group indicated that a higher body mass index in the day3 transfer group was the only significant difference (p = 0.006). Both fresh transfer groups had low live birth rates (LBRs) (4.5% vs. 7.4% p = 0.46). After extended culture, 65 cycles (48.1%) were cancelled because the embryos exhibited developmental arrest and 70 cycles (51.9%) grew to day4 or day5. Thirteen frozen embryo transfer (FET) cycles and 22 frozen blastocysts derived from MPEs were thawed. There were more high-quality embryos (p < 0.001), higher implantation rates (IRs) (p = 0.038), and higher LBRs (p = 0.042) for embryos that underwent FET cycles. MPES in extended culture transfer have favorable survival than MPES in day3 transfer., Conclusion: The extended culture of MPEs in fresh transfer cycles did not increase the LBR. However, younger females with the extended culture of MPEs followed by FET resulted in significantly higher LBRs and may be a feasible strategy to improve outcomes for patients with poor embryo quality. However, day3 embryo transfer may be a better choice if a fresh transfer is unrestricted and avoid the cycle cancellation. Extended culture may decrease to the transfer of developmental potential arrest embryos to patients., Competing Interests: Conflicts of interest The authors declare that they have no competing interests., (Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Scarce data are available on in-hospital hepatitis C virus (HCV) micro-elimination strategies. This pilot study was prospectively conducted to assess the outcomes of HCV in-hospital micro-elimination program (HCV-HELP) in a single center in Taiwan., Methods: The study included the HCV reflex test for plans A (hospital personnel), B (outpatient surveillance), C (a call-back system for anti-HCV+ patients), and D (surveillance of cancer patients prior to chemotherapy). The primary outcome measurement was that > 80% of eligible patients were enrolled in linkage-to-treat; the secondary outcome measurement was the surveillance efficacy., Results: We recruited 930, 6072, 2376 and 233 participants into plans A, B, C, and D, respectively, from Oct 2020 to May 2021. The anti-HCV-seropositivity prevalences were 0.22% for plan A, 4.3% for B, and 3.9% for D. Two staff members were identified as HCV-viremic in plan A; these staff members successfully achieved a sustained virological response (SVR). We identified 39, 95 and 2 HCV-viremic patients in plans B, C, and D, respectively. Of these 138 HCV-viremic patients, 135 (97.8%) received direct-acting antiviral therapy, and 134 achieved SVR. Two 4-month phases were stratified to compare efficacies in the liver clinic. In the late phase, the adjusted number of HCV-viremic patients was 4.36/10,000 outpatient visits (90/200,689), which was 3.18-fold higher than that of the early phase (1.37/10,000 outpatient visits [30/212,658], odds ratio 3.18; 95% confidence interval 2.10-4.81, p < 0.0001)., Conclusion: HCV micro-elimination is achievable at the hospital level as per the structured HCV-HELP study., (© 2021. Asian Pacific Association for the Study of the Liver.)

Background: Prisoners are at risk of hepatitis C virus (HCV) infection, especially among the people who inject drugs (PWID). We implemented an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic direct-acting antivirals (DAA) regimen, 12 wk of sofosbuvir/velpatasvir, in a PWID-dominant prison in Taiwan., Aim: To implement an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic DAA regimen in a PWID-dominant prison in Taiwan., Methods: HCV-viremic patients were recruited for onsite treatment program for HCV micro-elimination with a pangenotypic DAA regimen, 12 wk of sofosbuvir/ velpatasvir, from two cohorts in Penghu Prison, either identified by mass screen or in outpatient clinics, in September 2019. Another group of HCV-viremic patients identified sporadically in outpatient clinics before mass screening were enrolled as a control group. The primary endpoint was sustained virological response (SVR12, defined as undetectable HCV ribonucleic acid (RNA) 12 wk after end-of-treatment)., Results: A total of 212 HCV-viremic subjects were recruited for HCV micro-elimination campaign; 91 patients treated with sofosbuvir/Ledipasvir or glecaprevir/ pibrentasvir before mass screening were enrolled as a control. The HCV micro-elimination group had significantly lower proportion of diabetes, hypertension, hyperlipidemia, advanced fibrosis and chronic kidney diseases, but higher levels of HCV RNA. The SVR12 rate was comparable between the HCV micro-elimination and control groups, 95.8% (203/212) vs 94.5% (86/91), respectively, in intent-to-treat analysis, and 100% (203/203) vs 98.9% (86/87), respectively, in per-protocol analysis. There was no virological failure, treatment discontinuation, and serious adverse event among sofosbuvir/velpatasvir-treated patients in the HCV micro-elimination group., Conclusion: Outreach mass screening followed by immediate onsite treatment with a simplified pangenotypic DAA regimen, sofosbuvir/velpatasvir, provides successful strategies toward HCV micro-elimination among prisoners., Competing Interests: Conflict-of-interest statement: No author had reported a potential conflict of interest relevant to this work., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: To investigate the diagnostic abilities of the perfusion density (PD) and structural thickness parameters in the peripapillary and macular regions measured by optical coherence tomography angiography (OCTA) and optical coherence tomography (OCT) and to test if their diagnostic abilities of early glaucoma are different between highly myopic (HM) and non-highly myopic (NHM) patients. Methods: A total of 75 glaucoma patients and 65 controls were included in the analyses. The glaucoma detection abilities of macular PD and peripapillary PD, along with macular ganglion cell-inner plexiform layer (mGCIPL) thickness and peripapillary retinal nerve fiber layer (pRNFL) thicknesses were compared between the HM and NHM group. Diagnostic ability was assessed by area under the receiver operating characteristics (AUC) curves, adjusted by age, axial length, and signal strength. Results: The diagnostic ability of macular PD and mGCIPL thickness had no significant difference in both HM and NHM groups. However, the diagnostic ability of peripapillary PD except in the temporal section was significantly lower in the HM group than in the NHM group (all p < 0.05). The diagnostic ability of the superior, nasal, and average pRNFL thickness was also significantly lower in the HM group than in the NHM group (all p < 0.05). Conclusion: This study demonstrated that although peripapillary PD and macular PD were both significantly reduced in patients with highly myopia, the diagnostic ability of peripapillary PD in HM patients was significantly lower than that in NHM patients, while macular PD was not. Macular OCTA along with OCT imaging should be included in the imaging algorithm in early glaucoma diagnosis in highly myopic patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chang, Wang, Wang, Huang and Hsu.)

Background: Chronic hepatitis C virus (HCV) infection induces profound alterations in the cytokine and chemokine signatures in peripheral blood. Clearance of HCV by antivirals results in host immune modification, which may interfere with immune-mediated cancer surveillance. Identifying HCV patients who remain at risk of hepatocellular carcinoma (HCC) following HCV eradication remains an unmet need. We hypothesized that antiviral therapy-induced immune reconstruction may be relevant to HCC development., Aim: To investigate the impact of differential dynamics of cytokine expression on the development of HCC following successful antiviral therapy., Methods: One hundred treatment-naïve HCV patients with advanced fibrosis (F3/4) treated with direct-acting antivirals (DAAs) or peginterferon/ribavirin who achieved sustained virologic response [SVR, defined as undetectable HCV RNA throughout 12 wk (SVR12) for the DAA group or 24 wk (SVR24) for the interferon group after completion of antiviral therapy] were enrolled since 2003. The primary endpoint was the development of new-onset HCC. Standard HCC surveillance (abdominal ultrasound and α-fetoprotein) was performed every six months during the follow-up. Overall, 64 serum cytokines were detected by the multiplex immunoassay at baseline and 24 wk after end-of-treatment., Results: HCC developed in 12 of the 97 patients over 459 person-years after HCV eradication. In univariate analysis, the Fibrosis-4 index (FIB-4), hemoglobin A1c (HbA1c), the dynamics of tumor necrosis factor-α (TNF-α), and TNF-like weak inducer of apoptosis (TWEAK) after antiviral therapy were significant HCC predictors. The multivariate Cox regression model showed that ΔTNF-α (≤ -5.7 pg/mL) was the most important risk factor for HCC (HR = 11.54, 95%CI: 2.27-58.72, P = 0.003 in overall cases; HR = 9.98, 95%CI: 1.88-52.87, P = 0.007 in the interferon group). An HCC predictive model comprising FIB-4, HbA1c, ΔTNF-α, and ΔTWEAK had excellent performance, with 3-, 5-, 10-, and 13-year areas under the curve of 0.882, 0.864, 0.903, and 1.000, respectively. The 5-year accumulative risks of HCC were 0%, 16.9%, and 40.0% in the low-, intermediate-, and high-risk groups, respectively., Conclusion: Downregulation of serum TNF-α significantly increases the risk of HCC after HCV eradication. A predictive model consisting of cytokine kinetics could ameliorate personalized HCC surveillance strategies for post-SVR HCV patients., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: To understand how human papillomavirus (HPV) screening results, HPV-related knowledge and attitudes are related to vaccination intention in three cost ranges and the actual vaccination behavior in a community sample of men who have sex with men (MSM)., Methods: MSM aged 20 years of age or older were recruited between October 2015 and May 2016 from community health centers that provide HIV testing and consultation services in Southern Taiwan and on social media. MSM were seen at baseline and again at 6 months after baseline in a cohort study. The baseline study included 253 individuals; 182 of them returned for the 6th-month follow-up. At each visit, MSM were asked to receive HPV screening and filled out a questionnaire. Structural equation modeling was used to test whether attitudinal factors and HPV screening results from the baseline affect their self-reported actual vaccine uptake at the in 6 th -month follow-up., Results: Our research included 171 participants from the cohort because they had full information of the study variables (mean ± SD age = 29.21 ± 6.18). Our model showed good model fit using indices such as the comparative fit index (value = 0.998) and root mean square error of approximation (value = 0.013). HPV knowledge can predict those who have intention to take up HPV vaccine no matter what the price (p = .02), and then predict vaccine uptake at the follow-up (p < .001). A positive HPV screening result can predict vaccine uptake at the follow-up (p = .004)., Conclusion: Our findings highlight the impact of vaccine price and HPV screening results on the intention and uptake of HPV vaccine. It is important to raise awareness of HPV in male populations. Clinicians and health educators should establish a safe and private environment for male patients for inquiring about HPV vaccine and HPV-related cancers., (© 2021. The Author(s).)

Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110-CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure. Here, we reveal that the linear ubiquitin chain assembly complex (LUBAC) plays an essential role in ciliogenesis by targeting the CP110-CEP97 complex. LUBAC specifically generates linear ubiquitin chains on CP110, which is required for CP110 removal from the mother centriole in ciliogenesis. We further identify that a pre-mRNA splicing factor, PRPF8, at the distal end of the mother centriole acts as the receptor of the linear ubiquitin chains to facilitate CP110 removal at the initial stage of ciliogenesis. Thus, our study reveals a direct mechanism of regulating CP110 removal in ciliogenesis and implicates the E3 ligase LUBAC as a potential therapy target of cilia-associated diseases, including ciliopathies and cancers., (© 2021 Shen et al.)

Background and Aims: Regorafenib has demonstrated its survival benefit for unresectable hepatocellular carcinoma (uHCC) patients in a phase III clinical trial. We aimed to assess the efficacy and tolerability of regorafenib and the predictors of treatment outcomes in Taiwanese patients., Methods: We analyzed the survival, best overall response, predictors of treatment outcomes, and safety for uHCC patients who had tumor progression on sorafenib therapy and received regorafenib as salvage therapy between March 2018 and November 2020., Results: Eighty-six patients with uHCC were enrolled (median age, 66.5 years; 76.7% male). The median regorafenib treatment duration was 4.0 months (95% confidence interval [CI], 3.6-4.6). The most frequently reported adverse events were hand-foot skin reaction (44.2%), diarrhea (36.0%), and fatigue (29.1%). No unpredictable toxicity was observed during treatment. The median overall survival (OS) with regorafenib was 12.4 months (95% CI, 7.8-17.0) and the median progression-free survival (PFS) was 4.2 months (95% CI, 3.7-4.7). Of 82 patients with regorafenib responses assessable, 4 patients (4.9%) achieved a partial response, and 33 (40.2%) had stable disease, leading to a disease control rate (DCR) of 45.1% (n = 37). Patients possessing baseline AFP < 400 ng/ml exhibited a markedly longer median OS, median PFS, and higher DCR compared with their counterparts (15.7 vs. 8.1 months, 4.6 vs. 3.7 months, 60.9% vs. 27.5%, respectively). Despite possessing high baseline AFP levels, patients with early AFP response (>10% reduction at 4 weeks or >20% reduction at 8 weeks after regorafenib administration) exhibited comparable treatment outcomes to those with baseline AFP < 400 ng/ml., Conclusions: The results of this real-world study verified the tolerability and efficacy of regorafenib treatment for uHCC patients who failed prior sorafenib therapy, especially for those with lower baseline AFP levels or with early AFP response., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Avoiding aneuploid embryo transfers has been shown to improve pregnancy outcomes in patients with implantation failure and pregnancy loss. This retrospective cohort study aims to analyze the correlation of time-lapse (TL)-based variables and numeric blastocyst morphological scores (TLBMSs) with different mosaic levels. In total, 918 biopsied blastocysts with time-lapse assessments at a uniform time-point were subjected to next-generation sequencing-based preimplantation genetic testing for aneuploidy. In consideration of patient- and cycle-related confounding factors, all redefined blastocyst morphology components of low-grade blastocysts, that is, expansion levels (odds ratio [OR] = 0.388, 95% confidence interval [CI] = 0.217-0.695; OR = 0.328, 95% CI = 0.181-0.596; OR = 0.343, 95% CI = 0.179-0.657), inner cell mass grades (OR = 0.563, 95% CI = 0.333-0.962; OR = 0.35, 95% CI = 0.211-0.58; OR = 0.497, 95% CI = 0.274-0.9), and trophectoderm grades (OR = 0.29, 95% CI = 0.178-0.473; OR = 0.242, 95% CI = 0.143-0.411; OR = 0.3, 95% CI = 0.162-0.554), were less correlated with mosaic levels ≤20%, <50%, and ≤80% as compared with those of top-grade blastocysts ( p < 0.05). After converting blastocyst morphology grades into scores, high TLBMSs were associated with greater probabilities of mosaic levels ≤20% (OR = 1.326, 95% CI = 1.187-1.481), <50% (OR = 1.425, 95% CI = 1.262-1.608), and ≤80% (OR = 1.351, 95% CI = 1.186-1.539) ( p < 0.001). The prediction abilities of TLBMSs were similar for mosaic levels ≤20% (AUC = 0.604, 95% CI = 0.565-0.642), <50% (AUC = 0.634, 95% CI = 0.598-0.671), and ≤80% (AUC = 0.617, 95% CI = 0.576-0.658). In conclusion, detailed evaluation with TL monitoring at the specific time window reveals that redefined blastocyst morphology components and converted numeric TLBMSs are significantly correlated with all of the threshold levels of mosaicism. However, the performance of TLBMSs to differentiate blastocysts with aberrant ploidy risk remains perfectible., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Lee, Huang, Chen, Ho, Cheng, Lin, Chen, Lee and Lee.)

Objective: HCV prevails in uremic haemodialysis patients. The current study aimed to achieve HCV microelimination in haemodialysis centres through a comprehensive outreach programme., Design: The ERASE-C Campaign is an outreach programme for the screening, diagnosis and group treatment of HCV encompassing 2323 uremic patients and 353 medical staff members from 18 haemodialysis centres. HCV-viremic subjects were linked to care for directly acting antiviral therapy or received on-site sofosbuvir/velpatasvir therapy. The objectives were HCV microelimination (>80% reduction of the HCV-viremic rate 24 weeks after the end of the campaign in centres with ≥90% of the HCV-viremic patients treated) and 'No-C HD' (no HCV-viremic subjects at the end of follow-up)., Results: At the preinterventional screening, 178 (7.7%) uremic patients and 2 (0.6%) staff members were HCV-viremic. Among them, 146 (83.9%) uremic patients received anti-HCV therapy (41 link-to-care; 105 on-site sofosbuvir/velpatasvir). The rates of sustained virological response (SVR12, undetectable HCV RNA 12 weeks after the end of treatment) in the full analysis set and per-protocol population were 89.5% (94/105) and 100% (86/86), respectively, in the on-site treatment group, which were comparable with the rates of 92.7% (38/41) and 100% (38/38), respectively, in the link-to-care group. Eventually, the HCV-viremic rate decreased to 0.9% (18/1,953), yielding an 88.3% reduction from baseline. HCV microelimination and 'No-C HD' were achieved in 92.3% (12/13) and 38.9% (7/18) of the haemodialysis centres, respectively., Conclusion: Outreach strategies with mass screenings and on-site group treatment greatly facilitated HCV microelimination in the haemodialysis population., Clinicaltrialsgov Identifier: NCT03803410 and NCT03891550., Competing Interests: Competing interests: M-LY: research support from Abbvie, Abbott, BMS, Gilead, Merck and Roche. Consultant for Abbvie, Abbott, Ascletis, BMS, Gilead, J&J, Merck, Novartis, Pharmaessential and Roche. Speaker for Abbvie, Abbott, Ascletis, BMS, Gilead, Merck, Pharmaessential and Roche. C-FH: speaker for Abbvie, BMS, Gilead, Merck and Roche., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Osteoporotic intertrochanteric fractures often have postoperative complications despite a perfect reduction and an optimal fixation. We describe a simple technique using bone substitute augmentation and hypothesize that this method would prevent excessive sliding of the lag screw and potential subsequent complications., Methods: Between January 2009 and July 2017, patients with osteoporotic intertrochanteric fractures who were treated with a dynamic hip screw (DHS) were enrolled in this retrospective cohort study. DHS group patients received conventional DHS treatment and BSA-DHS group patients received bone-substitute augmented DHS treatment. Factors such as demographics, Parker and Palmer mobility scores, health-related quality of life (HRQoL) scores (short-form Health Survey-12 Physical Component Summary [SF-12-PCS], and SF-12 Mental Component Summary [SF-12-MCS]), morbidities, mortality, and radiographic outcomes were compared., Results: We enrolled 85 patients: DHS group = 37 and BSA-DHS group = 48. There was significant lag-screw sliding (mean: 9 mm and 3 mm, p < 0.001), varus collapse (mean: 7° and 3°, p < 0.001), and femoral shortening (mean: 10 mm and 3 mm, p < 0.001) in the DHS group compared to the BSA-DHS group. The ability to get around the house was significantly different between the DHS and BSA-DHS groups (p = 0.031) at 3 months. Postoperative scores were not significantly different after 6, 9 or 12 months, however. Scores for the ability to get out of the house and to go shopping and the SF-12-PCS were significantly worse in the DHS group at 3 and 6 months. Malunion and lag-screw cutout were also significantly worse in the DHS group (p = 0.037 and p = 0.033, respectively)., Conclusions: Bone-substitute augmentation appears effective to prevent typical postoperative complications experienced by the DHS group patients, and to improve functional outcomes. Additional prospective randomized large-scale cohort studies are necessary to confirm this conclusion., Level of Evidence: Therapeutic Level III., Competing Interests: Conflicts of interest All authors declare that they have no competing interests., (Copyright © 2020 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Computation of convolutional neural network (CNN) requires a significant amount of memory access, which leads to lots of energy consumption. As the increase of neural network scale, this phenomenon is further obvious, the energy consumption of memory access and data migration between on-chip buffer and off-chip DRAM is even much more than the computation energy on processing element array (PE array). In order to reduce the energy consumption of memory access, a better dataflow to maximize data reuse and minimize data migration between on-chip buffer and external DRAM is important. Especially, the dimension of input feature map (ifmap) and filter weight are much different for each layer of the neural network. Hardware resources may not be effectively utilized if the array architecture and dataflow cannot be reconfigured layer by layer according to their ifmap dimension and filter dimension, and result in a large quantity of data migration on certain layers. However, a thorough exploration of all possible configurations is time consuming and meaningless. In this paper, we propose a quick and efficient methodology to adapt the configuration of PE array architecture, buffer assignment, dataflow and reuse methodology layer by layer with the given CNN architecture and hardware resource. In addition, we make an exploration on the different combinations of configuration issues to investigate their effectiveness and can be used as a guide to speed up the thorough exploration process.

Background and Aim: Hepatitis B virus (HBV) surface antigen (HBsAg) seroreversion usually occurs during immunosuppressive therapy. The risk and factors of HBsAg seroreversion from resolved HBV infection in the general population remained unclear., Methods: This retrospective study enrolled subjects with resolved HBV infection and who had received at least two times of screening in a longitudinal community screening program. HBsAg, hepatitis B surface antibody (anti-HBs), and hepatitis C virus antibody (anti-HCV) were tested every time in all subjects. The primary endpoint was HBsAg seroreversion., Results: Of the 7630 subjects enrolled, 5158 (67.6%) subjects had positive anti-HBs at baseline. HBsAg seroreversion occurred in 84 subjects during 42 815-person-year follow-up with an annual incidence of 0.2% and a 10-year cumulative risk of 1.9%. Anti-HBV treatment-experienced subjects had a significantly higher risk of HBsAg seroreversion than anti-HBV treatment-naive subjects (83/310 [26.8%] vs 1/7320 [0.01%], P < 0.001). Lower rates of positive anti-HBs and anti-HCV were observed in anti-HBV treatment-experienced subjects who developed HBsAg seroreversion. Both positive anti-HBs (hazard ratio/95% confidence interval: 0.56/0.348-0.903, P = 0.017) and positive anti-HCV (hazard ratio/95% confidence interval: 0.08/0.030-0.234, P < 0.001) were independent factors of HBsAg seroreversion in anti-HBV treatment-experienced subjects. Less than 5% of the HBsAg seroreverters had clinical hepatitis flare at HBsAg seroreversion. The HBsAg titer was low, and only transient reappeared in most of the HBsAg seroreverters., Conclusions: Subjects with resolved HBV infection were at a minimal risk of HBsAg seroreversion, unless with prior anti-HBV treatment experience. Fortunately, even with a reappearance of HBsAg, it was transient and clinically non-relevant., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The term big kidney-little kidney syndrome in cats has been used for many years, but the definitions are not consistent and relevant research is limited., Objective: To determine the factors that differ between normal and BKLK cats, as well as to develop models for predicting the 30-day survival of cats with ureteral obstruction (UO)., Animals: Sixteen healthy cats and 64 cats with BKLK., Methods: Retrospective study. To define BKLK by reference to data from clinically healthy cats. The demographic and clinicopathological data among groups were statistically analyzed., Results: Big kidney-little kidney syndrome cats had higher blood urea nitrogen (BUN) (median [interquartile range] 69 [28-162] vs 21 [19-24] mg/dL, P < .001), creatinine (5.6 [1.9-13.3] vs 1.3 [1.05-1.40] mg/dL, P < .001), and white blood cells (10 800 [7700-17 500] vs 6500 [4875-9350] /μL, P < .001) and lower hematocrit (32.8 [27.1-38.4] vs 39.1 [38.1-40.4]%, P < .001), urine specific gravity (1.011 [1.009-1.016] vs 1.049 [1.044-1.057], P < .001) and pH (5.88 [5.49-6.44] vs 6.68 [6.00-7.18], P = .001) compared to the control cats. A lower body temperature (BT; 38.1 [37.9-38.2] vs 38.7 [38.3-39.2]°C, P = .009), higher BUN (189 [150-252] vs 91 [36-170] mg/dL, P = .04), and creatinine (15.4 [13.3-17.4] vs 9.0 [3.1-14.2] mg/dL, P = .03) were found among the UO cats that were not 30-day survivors. A combination of BUN, phosphorus, and BT can predict 30-day survival among UO cats with an area under receiver operating characteristic curve of 0.863. (P = .01)., Conclusion: An increase in the length difference between kidneys can indicate UO, but cannot predict outcome for BKLK cats., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

The increasing numbers of infections caused by multidrug-resistant (MDR) pathogens highlight the urgent need for new alternatives to conventional antibiotics. Antimicrobial peptides have the potential to be promising alternatives to antibiotics because of their effective bactericidal activity and highly selective toxicity. The present study was conducted to investigate the antibacterial, antibiofilm, and anti-adhesion activities of different CTP peptides (CTP: the original hybrid peptide cathelicidin 2 (1-13)-thymopentin (TP5); CTP-NH 2 : C-terminal amidated derivative of cathelicidin 2 (1-13)-TP5; CTPQ: glutamine added at the C-terminus of cathelicidin 2 (1-13)-TP5) by determining the minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), propidium iodide uptake, and analysis by scanning electron microscopy, transmission electron microscopy, and confocal laser scanning microscopy). The results showed that CTPs had broad-spectrum antibacterial activity against different gram-positive and gram-negative bacteria, with MICs against the tested strains varying from 2 to 64 μg/mL. CTPs at the MBC (2 × MIC 64 μg/mL) showed strong bactericidal effects on a standard methicillin-resistant Staphylococcus aureus strain ATCC 43300 after co-incubation for 6 h through disruption of the bacterial membrane. In addition, CTPs at 2 × MIC also displayed effective inhibition activity of several S. aureus strains with a 40-90% decrease in biofilm formation by killing the bacteria embedded in the biofilms. CTPs had low cytotoxicity on the intestinal porcine epithelial cell line (IPEC-J2) and could significantly decrease the rate of adhesion of S. aureus ATCC 43300 on IPEC-J2 cells. The current study proved that CTPs have effective antibacterial, antibiofilm, and anti-adhesion activities. Overall, this study contributes to our understanding of the possible antibacterial and antibiofilm mechanisms of CTPs, which might be an effective anti-MDR drug candidate.

Background: Histidine-tryptophan-ketoglutarate (HTK) is a solution commonly used for organ transplantation. However, there is no certified fixed regimen for on-pump heart surgery in neonates. We aimed to retrospectively evaluate the outcomes related to different HTK dosages and to analyze the safety of high-dosage perfusion., Methods: A total of 146 neonates who underwent on-pump heart surgery with single-shot HTK perfusion were divided into two groups according to HTK dosages: a standard-dose (SD) group (n = 63, 40 mL/kg < HTK ≤ 60 mL/kg) and a high-dose (HD) group (n = 83, HTK >60 mL/kg). Propensity score matching (PSM) was performed to control confounding bias., Results: The SD group had a higher weight (3.7 ± 0.4 vs. 3.4 ± 0.4 kg, P < 0.0001), a lower proportion of complete transposition of the great artery (69.8% vs. 85.5%, P = 0.022), a lower cardiopulmonary bypass (CPB) time (123.5 [108.0, 136.0] vs. 132.5 [114.8, 152.5] min, P = 0.034), and a lower aortic x-clamp time (82.9 ± 27.1 vs. 95.5 ± 26.0 min, P = 0.005). After PSM, 44 patients were assigned to each group; baseline characteristics and CPB parameters between the two groups were comparable. There were no significant differences in peri-CPB blood product consumption after PSM (P > 0.05). The incidences of post-operative complications were not significantly different between the two groups. There were no significant differences in ventilation time, intensive care unit stay, and post-operative hospital stay (P > 0.05). Follow-up echocardiography outcomes at 1 month, 3 to 6 months, and 1 year showed that left ventricular ejection fraction and end-diastolic dimension were comparable between the two groups., Conclusions: In neonatal on-pump cardiac surgery patients, single-shot HD (>60 mL/kg) HTK perfusion had a comparable heart protection effect and short-term post-operative prognosis as standard dosage perfusion of 40 to 60 mL/kg. Thus, this study provides supporting evidence of the safety of HD HTK perfusion., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Along with the rapid development of sensing systems and wireless transmission technology, the scope of application of the IoT has substantially increased, and research and innovation that integrate artificial intelligence. This study integrated civil engineering and electrical engineering to establish a universal and modularized long-term sensing system. Aiming at positive construction in civil engineering, the campus of National Taipei University of Technology was used as the experimental site as a green campus. This paper focused on the cooling effect of the green roof and the temperature difference of the solar panel to effectively isolate the direct sunlight on the roof of the building. To achieve long-term monitoring, energy consumption must be minimized. Considering that the distance between sensor nodes in the experimental site was over dozens of feet, LoRa transmission technology was selected for data transmission. LoRa only consumes a small amount of energy during data transmission, and it can freely switch between work modes, achieving optimal power utilization efficiency. The greening-related research results indicated that the shade from solar panels on the rooftop could effectively reduce the temperature increase caused by direct sunlight on concrete surfaces. The temperature reduction effect was positively correlated with whether the solar panels provided shade. After 1 week of monitoring, we observed that having plants on the rooftop for greening negatively correlated with temperature reduction efficiency. Permeable pavement on the ground was positively correlated with temperature reduction efficiency. However, its temperature reduction efficiency was inferior to that of solar panel shading. The temperature difference between high-rise buildings and the ground was approximately 1-2 °C. At the same elevation, the temperature difference between buildings with and without greening was approximately 0.8 °C. Regarding the sensing system designed for this site, both hardware and software could be flexibly set according to the research purposes, precision requirements of the sites, and the measurement scope, thereby enabling their application in more fields.

Six new cadinane-type sesquiterpenoids, named Chimnitensin A-F (1-6) were isolated from the leaves of Chimonanthus nitens Oliv. Their structures were elucidated by comprehensive spectroscopic analyses and comparison with structurally related known analogues. In vitro MTT assay showed that all six compounds had cytotoxicity against two selected human breast cancer cell lines (MDA-MB-468 and MDA-MB-231), which indicate their potential of developing into anticancer drugs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To evaluate the efficacy of shared decision-making (SDM) intervention among patients with lumbar degenerative diseases (LDDs) in terms of decision self-efficacy, control preferences, SDM process, decision satisfaction, and conflict., Methods: A total of 130 outpatients with LDDs recruited from orthopedic or rehabilitation clinics were randomly assigned to the SDM intervention (n = 67) or comparison (n = 63) groups. Patients in the intervention group received decision aids (DAs) with decision coaching and those in controlled group received standard educational materials from a health educator. The primary outcome was decision self-efficacy, and secondary outcomes were control preference, SDM process, conflict, and satisfaction., Results: The SDM intervention significantly improved decision self-efficacy (mean difference [MD] = 7.1, 95% confidence interval [CI]: 1.7-12.5, partial η 2 = 0.05) and reduced conflict (MD = -7.0, 95% CI: -12.2 to -1.9, partial η 2 = 0.06), especially in patients without family involvement, compared with the health education group. However, no significant between-group differences were observed in other outcomes., Conclusion: SDM intervention improved SDM self-efficacy and reduced conflict in patients with LDDs., Practice Implications: Clinicians can integrate DAs and decision coaching in SDM conversations. SDM intervention seems to engage patients in decision-making, especially those without family involvement., Competing Interests: Declarations of Interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Cancer stem cells (CSCs) are key regulators in the processes of tumor initiation, progression, and recurrence. The mechanism that maintains their stemness remains enigmatic, although the role of several long noncoding RNAs (lncRNAs) has been highlighted in the pancreatic cancer stem cells (PCSCs). In this study, we first established that PCSCs overexpressing lncRNA NORAD, and then investigated the effects of NORAD on the maintenance of PCSC stemness., Methods: Expression of lncRNA NORAD, miR-202-5p and ANP32E in PC tissues and cell lines was quantified after RNA isolation. Dual-luciferase reporter assay, RNA pull-down and RIP assays were performed to verify the interactions among NORAD, miR-202-5p and ANP32E. We then carried out gain- and loss-of function of miR-202-5p, ANP32E and NORAD in PANC-1 cell line, followed by measurement of the aldehyde dehydrogenase activity, cell viability, apoptosis, cell cycle distribution, colony formation, self-renewal ability and tumorigenicity of PC cells., Results: LncRNA NORAD and ANP32E were upregulated in PC tissues and cells, whereas the miR-202-5p level was down-regulated. LncRNA NORAD competitively bound to miR-202-5p, and promoted the expression of the miR-202-5p target gene ANP32E thereby promoting PC cell viability, proliferation, and self-renewal ability in vitro, as well as facilitating tumorigenesis of PCSCs in vivo., Conclusion: Overall, lncRNA NORAD upregulates ANP32E expression by competitively binding to miR-202-5, which accelerates the proliferation and self-renewal of PCSCs., (© 2021. The Author(s).)

Purpose: This retrospective study aimed to compare the efficacy of intravitreal ranibizumab (IVR) and intravitreal dexamethasone implant (IDI) for pseudophakic vitrectomized eyes with diabetic macular edema (DME) in a single institution., Methods: Pseudophakic vitrectomized eyes with treatment-naïve center-involved DME were enrolled, with one eye in each patient. They were divided into two groups: one group receiving IDI every 3 to 4 months and another group receiving IVR using 3 monthly plus treat-and-extend injections, all with monthly follow-up for 6 months. Switch of intravitreal drugs or deferred macular laser was not allowed. Primary outcome measures included change in central foveal thickness (CFT) in 1 mm by spectral-domain optical coherence tomography and best-corrected visual acuity (BCVA) at Month 6., Results: Twenty-two eyes were included in the IDI group and 26 eyes in the IVR group. The baseline demographics, glycosylated hemoglobin level, intraocular pressure (IOP), BCVA, and CFT did not significantly differ ( p > 0.05). Compared to baseline data, CFT decreased and BCVA improved significantly after either IDI or IVR at Month 6 ( p < 0.05). Significantly better mean final BCVA (0.38 logMAR vs. 0.62 logMAR, p =0.04), more mean visual gain (-0.30 logMAR vs. -0.15 logMAR, p =0.02), lower mean final CFT (310.9  μ m vs. 384.2  μ m, p =0.04), and larger mean CFT decrease (-150.0  μ m vs. -60.1  μ m, p =0.03) were found in the IDI group compared to those in the IVR group. A smaller mean treatment number (2.6 vs. 5.6, p < 0.001) and higher rate of postinjection ocular hypertension requiring topical hypotensive agent therapy (27.3% vs. 0%, p =0.0002) were demonstrated in the IDI group than those in the IVR group., Conclusion: We concluded that IDI and IVR can both effectively treat vitrectomized eyes with DME. Dexamethasone implants had significantly better visual/anatomical improvement, smaller treatment number, and higher rate of elevated IOP after injection than IVR in pseudophakic vitrectomized eyes with DME in a 6-month period., Competing Interests: All authors have no proprietary or commercial interest in any materials discussed in this article. The authors declare no competing financial and/or nonfinancial interests in relation to this study and manuscript., (Copyright © 2021 Jia-Kang Wang et al.)

Escherichia coli causing urinary tract infections (UTIs) are one of the most common outpatient bacterial infections. This study aimed to compare the characteristics of E. coli isolated from UTI patients in a single medical center in 2009-2010 (n = 504) and 2020 (n = 340). The antimicrobial susceptibility of E. coli was determined by the disk diffusion method. PCRs were conducted to detect phylogenetic groups, ST131, K1 capsule antigen, and 15 virulence factors. Phylogenetic group B2 dominated in our 2009-2010 and 2020 isolates. Moreover, no phylogenetic group E strains were isolated in 2020. E. coli isolates in 2020 were more susceptible to amoxicillin, ampicillin/sulbactam, cefuroxime, cefmetazole, ceftazidime, cefoxitin, tetracycline, and sulfamethoxazole/trimethoprim, compared to the isolates in 2009-2010. Extensively drug-resistant (XDR)- E. coli in 2009-2010 were detected in groups B1 (5 isolates), B2 (12 isolates), F (8 isolates), and unknown (1 isolate). In 2020, XDR- E. coli were only detected in groups A (2 isolates), B2 (5 isolates), D (1 isolate), and F (4 isolates). The prevalence of virulence factor genes aer and fimH were higher in E. coli in 2009-2010 compared to those in 2020. In contrast, afa and sat showed higher frequencies in E. coli isolates in 2020 compared to E. coli in 2009-2010.

Background: With the development of the economy and improvements in living standards, the incidences of diabetes mellitus (DM) and diabetic retinopathy (DR), which is a complication of DM, are on the rise., Aim: To analyze early DR in patients with macular zone changes in biological images using optical coherence tomography angiography., Methods: A prospective case study was performed on 59 participants: 35 healthy eyes (control group), 35 eyes with diabetes but no DR group (no DR group), and 35 eyes with mild DR (NPDR group). All quantitative comparisons of parameters, including the fovea vascularity area, circularity index, and vascular complexity parameters, were performed using a biological image analysis software., Results: The foveal avascular zone (FAZ) area, FAZ circularity index, number of branches in the area, and the total of the single branches' length in the area was 0.366 ± 0.031, 0.834 ± 0.037, 3241.8 ± 268.3, and 3.860 × 10 7 ± 0.194 × 10 7 , and 0.421 ± 0.030, 0.739 ± 0.023, 2956.6 ± 476.4, and 3.177 × 10 7 ± 0.161 × 10 7 in the no DR group and the NPDR group, respectively, which were significantly different from the corresponding parameters of the control group ( P < 0.05). Moreover, there were significant differences between these two groups ( P < 0.05)., Conclusion: This study shows that early microcirculation changes in the macular area of the retina is associated with disease progression. Early changes in DR can be analyzed using optical coherence tomography angiography., Competing Interests: Conflict-of-interest statement: None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Despite the success in developing various pharmaceutical formulations, most of the active pharmaceutical ingredients (APIs)/drugs, according to the Biopharmaceutics Classification System (BCS), often suffer from various intrinsic limitations of solubility and permeability, substantially hindering their bioavailability in vivo. Regardless of the fact that the availability of different particle fabrication approaches (top-down and bottom-up) towards pharmaceutical manufacturing, the supercritical fluid (SCF) technology has emerged as one of the highly effective substitutes due to the environmentally benign nature and processing convenience, as well as the economically promising character of SCFs. The exceptional features of SCFs have endowed the fabrication of various APIs either solely or in combination with the compatible supramolecular species towards achieving improved drug delivery. Operating such APIs in high-pressure conditions often results in arbitrary-sized particulate forms, ranging from micron-sized to sub-micron/nano-sized particles. Comparatively, these SCF-processed particles offer enhanced tailorable physicochemical and morphological properties (size, shape, and surface), as well as improved performance efficacy (bioavailability and therapy) over the unprocessed APIs. Although the "carrier-based" delivery is practical among diverse delivery systems, the direct fabrication of APIs into suitable particulate forms, referred to as "carrier-free" delivery, has increased attention towards improving the bioavailability and conveying a high payload of the APIs. This review gives a comprehensive emphasis on the SCF-assisted fabrication of diverse APIs towards exploring their great potential in drug delivery. Initially, we discuss various challenges of drug delivery and particle fabrication approaches. Further, different supercritical carbon dioxide (SC-CO 2 )-based fabrication approaches depending on the character of SCFs are explicitly described, highlighting their advantages and suitability in processing diverse APIs. Then, we provide detailed insights on various processing factors affecting the properties and morphology of SCF-processed APIs and their pharmaceutical applications, emphasizing their performance efficacy when administered through multiple routes of administration. Finally, we summarize this compilation with exciting perspectives based on the lessons learned so far and moving forward in terms of challenges and opportunities in the scale-up and clinical translation of these drugs using this innovative technology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) is a heterogeneous tumor with an increased incidence worldwide accompanied by high mortality and dismal prognosis. Emerging evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes possess protective effects against various human diseases by transporting microRNAs (miRNAs or miRs). We aimed to explore the role of exosomal miR-15a derived from MSCs and its related mechanisms in HCC. Exosomes were isolated from transduced MSCs and co-incubated with Hep3B and Huh7 cells. miR-15a expression was examined by RT-qPCR in HCC cells, MSCs, and secreted exosomes. CCK-8, transwell, and flow cytometry were used to detect the effects of miR-15a or spalt-like transcription factor 4 (SALL4) on cell proliferative, migrating, invasive, and apoptotic properties. A dual-luciferase reporter gene assay was performed to validate the predicted targeting relationship of miR-15a with SALL4. Finally, in vivo experiments in nude mice were implemented to assess the impact of exosome-delivered miR-15a on HCC. The exosomes from MSCs restrained HCC cell proliferative, migrating, and invasive potentials, and accelerated their apoptosis. miR-15a was expressed at low levels in HCC cells and could bind to SALL4, thus curtailing the proliferative, migrating, and invasive abilities of HCC cells. Exosomes successfully delivered miR-15a to HCC cells. Exosomal miR-15a depressed tumorigenicity and metastasis of HCC tumors in vivo. Overall, exosomal miR-15a from MSCs can downregulate SALL4 expression and thereby retard HCC development., (© 2021. The Author(s).)

The purpose of this study is to investigate the mediating role of exercise value cognition between family function (FF) and exercise behavior and the moderating role of an only-child status. A questionnaire survey was conducted on 504 Chinese college students using the FF scale, the exercise value cognition scale, and the exercise behavior scale. The analysis yielded four main findings. (1) There are significant differences between an only-child and a non-only-child for negative exercise behavior and FF. The only-child group has a higher average FF score and a lower average negative exercise score. (2) Exercise behavior and four of its dimensions-exercise autonomy, attention control, exercise planning, and situational induction-are each significantly positively correlated with FF and exercise value cognition. (3) FF is a significantly positive predictor of exercise behavior, both directly and through exercise value cognition, which plays a partial mediating role. (4) Only-child status significantly moderates the mediating effect of exercise value cognition in the link between FF and exercise behavior. The intergroup differences mainly manifest in the influence of FF on exercise behavior and the influence of exercise value cognition on exercise behavior. In the only-child subsample, exercise value cognition plays a complete mediating role. The results of the current study demonstrated the important role that FF and exercise value cognition played in promoting the exercise behavior of college students. These findings have important implications for exercise behavior in adolescents by maintaining sound communication between family members and developing a healthy lifestyle or value cognition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Wu, Yang and Li.)

Background: For women undergoing in vitro fertilization (IVF), the clinical benefit of embryo transfer at the blastocyst stage (Day 5) versus cleavage stage (Day 3) remains controversial. The purpose of this study is to compare the implantation rate, clinical pregnancy rate and odds of live birth of Day 3 and Day 5 embryo transfer, and more importantly, to address the issue that patients were chosen to receive either transfer protocol due to their underlying clinical characteristics, i.e., confounding by indication., Methods: We conducted a retrospective cohort study of 9,090 IVF cycles collected by Lee Women's Hospital in Taichung, Taiwan from 1998 to 2014. We utilized the method of propensity score matching to mimic a randomized controlled trial (RCT) where each patient with Day 5 transfer was matched by another patient with Day 3 transfer with respect to other clinical characteristics. Implantation rate, clinical pregnancy rate, and odds of live birth were compared for women underwent Day 5 transfer and Day 3 transfer to estimate the causal effects. We further investigated the causal effects in subgroups by stratifying age and anti-Mullerian hormone (AMH)., Results: Our analyses uncovered an evidence of a significant difference in implantation rate (p=0.04) favoring Day 5 transfer, and showed that Day 3 and Day 5 transfers made no difference in both odds of live birth (p=0.27) and clinical pregnancy rate (p=0.11). With the increase of gestational age, the trend toward non-significance of embryo transfer day in our result appeared to be consistent for subgroups stratified by age and AMH, while all analyses stratified by age and AMH were not statistically significant., Conclusions: We conclude that for women without strong indications for Day 3 or Day 5 transfer, there is a small significant difference in implantation rate in favor of Day 5 transfer. However, the two protocols have indistinguishable outcomes on odds of live birth and clinical pregnancy rate., (© 2021. The Author(s).)

Objective: The purpose of this review was to evaluate the effects of sling exercise on pain intensity, disability, and health-related quality of life in adults with neck pain., Methods: The Cochrane Central Register of Controlled Trials, EMBASE, Physiotherapy Evidence Database (PEDro), and 6 other databases were searched from inception to July 2020. The reference lists of relevant articles to identify additional trials were also screened. Randomized controlled trials were included if they investigated the effects of sling suspension therapy in patients with neck pain, including mechanical neck disorders, cervicogenic headache, and neck disorders with radicular findings. Studies were required to be published in English or Chinese. The methodological quality and levels of evidence of studies were assessed using the PEDro scale and the Grading of Recommendations Assessment, Development and Evaluation approach, respectively. The random-effects model was used to perform meta-analyses., Results: Eleven randomized controlled trials were included (n = 595). The mean total PEDro score was 4.64 (SD = 1.21) of 10, which indicated a fair methodological quality. The intervention groups showed significant improvements in pain intensity (SMD = -1.23; 95% CI = -1.88 to -0.58) immediately postintervention compared with the control groups. No significant effects were found for disability, cervical range of motion, and health-related quality of life. However, sensitivity analyses revealed significant short-term improvements in pain intensity, disability, and cervical range of motion and sustained effects on disability at intermediate-term follow-up., Conclusion: Sling exercise appears to be beneficial for improvements in pain intensity (moderate- to low-level evidence) among patients with neck pain. However, no definitive conclusion could be made regarding the effect of sling exercise for neck pain due to methodological limitations and high heterogeneity in the included studies., Impact: This review provides overall moderate- to very low-level evidence for health care professionals who may consider including sling exercise in the intervention program for patients with neck pain., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Cardiac flow closely interact with function, however, the correlation of right ventricular (RV) flow and function remains unknown, thus our objective is to observe right ventricular flow with four-dimensional phase-contrast cardiovascular magnetic resonance imaging (4D flow CMR) in patients with pulmonary arterial hypertension (PAH) and to analyze flow components with RV function and hemodynamics., Methods: This study retrospectively enrolled 30 patients with PAH (mean age: 49±13 years, 16 females) and 14 age- and sex-matched healthy volunteers as controls (mean age: 44±12 years, 9 females). All patients who underwent CMR and right heart catheterization (RHC) within 1 week between January 2019 and July 2020 were included. Hemodynamics were measured with RHC. RV flow components, including the percentages of direct flow (RVPDF), retained inflow (RVPRI), delayed ejection flow (RVPDEF) and residual volume (RVPRVo) were quantified using 4D flow CMR. The associations between RV flow components and other CMR metrics, clinical data, and hemodynamics were analyzed by Spearman's correlation analysis., Results: In patients with PAH, RVPDF was decreased and RVPRVo was increased compared with the normal control group. The sum of RVPDF and RVPDEF RV was significantly correlated with RV ejection fraction (RVEF) (r=0.802, P<0.001), and there was no notable difference between RVEF and the sum of RVPDF and RVPDEF (t=0.251, P=0.831). Both RVPDF and RVPRVo were correlated (in opposite directions) with the RV end-diastolic volume index, RV end-systolic volume index, RV global longitudinal strain, and RVEF. RVPDF was negatively correlated with pulmonary vascular resistance (PVR), and positively correlated with cardiac output and cardiac index. RVPRVo was positively correlated with PVR and negatively correlated with cardiac output and cardiac index., Conclusions: RV blood flow components qualified with 4D flow CMR is a valuable noninvasive method for the assessment of RV function and hemodynamics in patients with PAH., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-20-1267). The authors have no conflicts of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Recent studies have emphasized microRNAs (miRs) as crucial regulators in the occurrence and development of pancreatic cancer that continues to be one of the deadliest malignancies with few effective therapies. The study aimed to investigate the functional role of miR-873 and its associated mechanism to unravel the biological characteristics of pancreatic cancer stem cells in tumor growth. The expression patterns of pleckstrin-2 (PLEK2) and miR-873 were detected in the pancreatic cancer tissues. Then to further investigate specific role of miR-873, the pancreatic cancer stem cells were treated with miR-873 mimic, PLEK2, small interfering RNA against PLEK2, LY294002 (inhibitor of phosphatidylinositol 3-kinase/protein kinase B [PI3K/AKT] pathway) to detect the relative gene expression as well as their effects on cell self-renewal, proliferation and apoptosis. Finally, the tumor formation in nude mice was measured to verify the preceding results in vivo. Pancreatic cancer tissues exhibited a decline of miR-873 expression and an enhancement of PLEK2 expression. miR-873 targeted PLEK2 and downregulated its expression, leading to inhibition of PI3K/AKT pathway. Overexpressed miR-873 or silenced PLEK2 inhibited the self-renewal and proliferation while promoting the apoptosis of pancreatic cancer stem cells. Tumor formation was inhibited by overexpressed miR-873 or silenced PLEK2 in nude mice. Overall, miR-873 can suppress the self-renewal and proliferation of pancreatic cancer stem cells by blocking PLEK2-dependent PI3K/AKT pathway. Hence, this study contributes to understanding the role of miR-873 in pancreatic cancer stem cells and its underlying molecular mechanisms to aid in the development of effective pancreatic cancer therapeutics., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Aim: Hemodialysis patients are at increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Both HBV and HCV infections lead to risks of end-stage liver diseases and extrahepatic manifestations. This study aimed to investigate hepatic and extrahepatic comorbidities in hemodialysis patients with HBV or HCV infections compared with those without viral hepatitis., Methods: A total of 1910 hemodialysis patients, including 159 HCV viremic patients (HCV group), 217 seropositive for HBV surface antigen (HBsAg, HBV group) and 1534 seronegative for both anti-HCV and HBsAg (non-B and non-C [NBNC] group), from 23 hemodialysis centers were enrolled. Comorbidities were classified into 10 categories by the International Classification of Diseases-10th Revision., Results: Among the 1910 patients, the mean age was 64.6 years, and 52.7% were male patients. A total of 1834 (96%) patients had at least one comorbidity, and the mean number of comorbidities was 2.9 ± 1.5 per person. The three most common comorbidities were hypertension, diabetes, and ischemic heart diseases. The mean number of comorbidities per person was significantly higher in the HCV group (3.3 ± 1.7) than in the HBV (2.7 ± 1.5, P < 0.001) and NBNC groups (2.9 ± 1.5, P = 0.004), mainly due to the higher prevalence of ischemic heart disease, respiratory disorders, and mental/behavioral disorders. The HBV and NBNC groups exhibited comparable burdens of comorbidities., Conclusions: Hemodialysis patients had a high prevalence of multiple comorbidities. Hemodialysis patients with HCV exhibited a higher burden of comorbidities, especially ischemic heart diseases, respiratory disorders, and mental/behavioral disorders, than HBV and NBNC patients did., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

As organ-specific three-dimensional cell clusters derived from cancer tissue or cancer-specific stem cells, cancer-derived organoids are organized in the same manner of the cell sorting and spatial lineage restriction in vivo, making them ideal for simulating the characteristics of cancer and the heterogeneity of cancer cells in vivo. Besides the applications as a new in vitro model to study the physiological characteristics of normal tissues and organs, organoids are also used for in vivo cancer cell characterization, anti-cancer drug screening, and precision medicine. However, organoid cultures are not without limitations, i.e., the lack of nerves, blood vessels, and immune cells. As a result, organoids could not fully replicate the characteristics of organs but partially simulate the disease process. This review attempts to provide insights into the organoid models for cancer precision medicine., (Copyright © 2021. Published by Elsevier Inc.)

Selective laser trabeculoplasty (SLT) is a useful treatment for intraocular pressure (IOP) control. However, there are only a few reports which compare the outcomes of SLT between primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). We compared the efficacy of SLT for patients with PACG following phacoemulsification with POAG receiving maximal medical therapy (MMT). Consecutive glaucoma patients followed up for at least 1 year after SLT were retrospectively evaluated and IOP reductions at 6 months and 12 months were analyzed. Seventy-six patients were included in the analyses. The baseline IOPs in the POAG and PACG group were 18.5 ± 3.3 mmHg and 16.9 ± 2.5 mmHg, respectively, with 2.8 ± 0.9 and 2.7 ± 0.8 types of IOP lowering medication. The average IOP at the 6-month and 12-month follow-up after SLT was significantly decreased and comparable in both the POAG and PACG groups. For those with a low baseline IOP, the effect of SLT on IOP reduction at 12 months was significantly better in the PACG than in the POAG group ( p = 0.003). IOP reduction at 6 and 12 months after SLT was significantly greater in those with a high baseline IOP than those with a low baseline IOP ( p < 0.0065). In summary, the one-year efficacy of SLT was equivalent in POAG and pseudophakic PACG patients receiving MMT; however, SLT was more effective in eyes with PACG than eyes with POAG when focusing on those with a lower baseline IOP.

Chemotherapy is one of the main treatments for cancer, especially for advanced cancer patients. In the past decade, significant progress has been made with the research into the molecular mechanisms of cancer cells and the precision medicine. The treatment on cancer patients has gradually changed from cytotoxic chemotherapy to precise treatment strategy. Research into anticancer drugs has also changed from killing effects on all cells to targeting drugs for target genes. Besides, researchers have developed the understanding of the abnormal physiological function, related genomics, epigenetics, and proteomics of cancer cells with cancer genome sequencing, epigenetic research, and proteomic research. These technologies and related research have accelerated the development of related cancer drugs. In this review, we summarize the research progress of anticancer drugs, the current challenges, and future opportunities., Competing Interests: None., (AJCR Copyright © 2021.)

Background & Aims: Hepatocellular carcinoma (HCC) is a fatal disease characterized by vast molecular heterogeneity. Although major advances in tumour genetics has led to the identification of new biomarkers, the prognosis of patients with HCC remains dismal., Methods: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blot (WB) were used to evaluate meiosis-specific nuclear structural 1 (MNS1) expression in HCC cells. Immunohistochemistry staining was used to evaluate MNS1 expression in HCC tissues. Clinical significance of MNS1 was evaluated by Cox regression analysis. Transwell assays were conducted to assess cells migration ability. Cell counting kit-8 and colony formation assays were performed to detect cells proliferation ability. NOD/SCID/γc(null) (NOG) mice model was adopted to investigate functions of MNS1 in vivo., Results: The expression of MNS1, which is elevated in most HCC tissues, correlated with poor survival in HCC patients. Functional experiments revealed the oncogenic role of MNS1, which promotes HCC growth and metastasis through AKT-dependent modulation of β-catenin. β-Catenin expression was crucial for MNS1's oncogenic effects. MNS1 indirectly translocated β-catenin from the cytoplasm to the nucleus via the MNS1-GSK3β axis., Conclusions: MNS1 promotes HCC growth and metastasis via activating PI3K/AKT signalling and may serve as an important prognostic biomarker as well as potential novel therapeutic target for HCC., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We examined the effect of microRNA-320b (miR-320b) on tumor growth and angiogenesis in lung cancer and also determined its downstream molecular mechanisms. Lung cancer tissues and adjacent non-cancerous tissues were collected from 66 patients with lung cancer. miR-320b expression was experimentally determined to be expressed at low level in cancer tissues. The results of gain-of-function experiments suggested that miR-320b overexpression suppressed cancer cell invasion, tube formation, tumor volume and angiogenesis in xenografted nude mice. Hepatocyte nuclear factor 4 gamma (HNF4G) was identified as a target of miR-320b based on in silico analysis. Dual-luciferase reporter gene assays further identified the binding relationship between HNF4G and miR-320b. Lung cancer tissues exhibited increased expression of HNF4G and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Meanwhile, HNF4G knockdown suppressed IGF2BP2 expression, thereby repressing cancer cell invasion and tube formation. Furthermore, IGF2BP2 modified m6A to increase the expression of thymidine kinase 1 (TK1), thus promoting angiogenesis. In nude mice, restoration of TK1 reversed the suppressive effect of miR-320b overexpression on tumor growth rate and CD31 expression. In conclusion, miR-320b suppresses lung cancer growth and angiogenesis by inhibiting HNF4G, IGF2BP2 and TK1., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Uraemic patients undergoing haemodialysis are at high risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We aimed to evaluate the evolutionary seroprevalence of viral hepatitis and the gap in HCV care cascades in this special population by a large-scale surveillance study in Taiwan. Uraemic patients on maintenance haemodialysis from 22 sites (FORMOSA-LIKE group) in 2012 (n = 1,680) and 2019 (n = 2,326) were recruited for this study. The distributions and sequential changes of viral hepatitis markers were analysed. The prevalence of anti-HCV antibody and hepatitis B surface antigen (HBsAg) seropositivity was 13.6% (316/2326) and 11.5% (267/2326), respectively, in 2019 compared with 17.3% (290/1680, P = .002) and 13.6% (229/1680, P = .046), respectively, in 2012. The HCV-viremic rate among anti-HCV-seropositive patients was significantly lower in 2019 than in 2012 (56.3% [178/316] vs. 73.8% [214/290], P < .001). The HCV treatment rate increased from 2.3% (5/217) in 2012 to 21.7% (49/226) in 2019 (P < .001). In the sequential analysis of the 490 patients who participated in both screens, 17 of the 55 HCV-viremic patients became HCV RNA seronegative, including 13 by antivirals and four spontaneously. By contrast, one anti-HCV-seropositive but nonviremic patient became viremic, and six anti-HCV-seronegative patients became anti-HCV-seropositive in 2019. The annual incidence of new HCV was 0.2%/year. Seven HBsAg-seropositive patients experienced HBsAg loss (1.25%/year). Two patients had new anti-HBc seropositivity (new HBV exposure: 0.57%/year). The seroprevalence of viral hepatitis decreased in an 8-year follow-up but remained prevalent, and the treatment of HCV infection was underutilized in uraemic patients. Additional efforts are needed to enhance the HCV treatment uptake of uraemic patients. Clinical Trial IDs: NCT03803410, NCT01766895., (© 2021 John Wiley & Sons Ltd.)

Hepatocellular carcinoma (HCC) remains an extremely lethal disease worldwide. High-throughput methods have revealed global transcriptome dysregulation; however, a comprehensive investigation of the complexity and behavioral characteristics of the competing endogenous RNA (ceRNA) network in HCC is lacking. In this study, we extracted the transcriptome (RNA) sequencing data of 371 HCC patients from The Cancer Genome Atlas platform. With the comparison of the high Myc expression (Myc high ) tumor and low Myc expression (Myc low ) tumor groups in HCC, we identified 1,125 differentially expressed (DE) mRNAs, 589 long non-coding RNAs (lncRNAs), and 93 microRNAs (miRNAs). DE RNAs predicted the interactions necessary to construct an associated Myc ceRNA network, including 19 DE lncRNAs, 5 miRNAs, and 72 mRNAs. We identified a significant signature (long intergenic non-protein-coding [LINC] RNA 2691 [LINC02691] and LINC02499) that effectively predicted overall survival and had protective effects. The target genes of microRNA (miR)-212-3p predicted to intersect with DE mRNAs included SEC14-like protein 2 (SEC14L2) and solute carrier family 6 member 1 (SLC6A1), which were strongly correlated with survival and prognosis. With the use of the lncRNA-miRNA-mRNA axis, we constructed a ceRNA network containing four lncRNAs (LINC02691, LINC02499, LINC01354, and NAV2 antisense RNA 4), one miRNA (miR-212-3p), and two mRNAs (SEC14L2 and SLC6A1). Overall, we successfully constructed a mutually regulated ceRNA network and identified potential precision-targeted therapies and prognostic biomarkers., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)