Dip coating of shear-thinning particulate suspensions.

Dip coating a planar substrate with a suspension of particles in a shear-thinning liquid will entrain particles in the liquid film, facilitating filtration and sorting of particles. Experiments were performed for both monodisperse and bidisperse particle suspensions of shear-thinning Xanthan Gum solutions. Particle entrainment occurs when the coating thickness at the stagnation point of the thin film flow is larger than the particle diameter. A model is developed to predict the entrainment criteria using lubrication theory applied to an Ostwald power-law fluid which yields a modified Landau-Levich-Derjaguin (LLD) law governing the coating film thickness that depends upon a properly defined capillary number Ca. The critical withdrawal velocity for particle entrainment depends upon the particle size and fluid rheology through a relationship between Ca and the bond number Bo, which agrees well with our model predictions and prior experimental results of A. Sauret et al. Phys. Rev. Fluids, 2019, 4, 054303 for the limiting case of Newtonian suspensions. Single particle entrainment and particle clustering is observed for monodisperse suspensions, which depends on Ca and the particle volume fraction ϕ. In bidisperse suspensions, particle sorting can occur whereby only the smaller particles are entrained in the film over an active filtration range of Ca and Bo, which also agrees well with our model predictions.

Exercise to socialize? Bidirectional relationships between physical activity and loneliness in middle-aged and older American adults.

Physical inactivity and loneliness are both associated with health risks and can affect each other through various social and behavioral mechanisms. However, current evidence on this relationship is equivocal and mostly based on cross-sectional data. This longitudinal study aimed to determine whether current levels of physical activity (moderate and vigorous intensity) and loneliness are associated with future respective states of themselves and each other. We used data from waves 6-14 (2002-2018) of the Health and Retirement Study (n = 20 134) in a mixed-effects and random-intercept cross-lagged panel model. Analysis showed that current loneliness and physical activity were associated with each future respective state. Additionally, weekly participation in moderate-intensity, but not vigorous-intensity, physical activity was associated with a lower likelihood of becoming lonely in the future (relative risk [RR] = 0.94; 95% CI, 0.90-0.99). However, changes in physical activity were not associated with deviation from a person's typical level of loneliness (for vigorous intensity, mean deviation [MD] = 0.00; 95% CI: -0.04 to 0.03; for moderate-intensity, MD = 0.01; 95% CI: -0.03 to 0.04). Loneliness was not associated with moderate- or vigorous-intensity physical activity in subsequent waves. This suggests that while lower physical activity levels can be associated with future loneliness, changing levels of physical activity has little impact on loneliness at the individual level.

Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

The Joint Effect of Body Mass Index and Serum Lipid Levels on Incident Dementia among Community-Dwelling Older Adults.

OBJECTIVES: This study aimed to explore the joint effect of body mass index (BMI) and serum lipids levels on incident dementia. METHODS: We prospectively followed up with 1,627 dementia-free community residents aged ≥60 for 5.7 years on average. At baseline, weight, and height were measured, and total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were detected in serum. Demographic characteristics were collected through questionnaires. Dementia was based on consensus diagnosis of neurologists and neuropsychologists using DSM-IV criteria. Additive Cox proportional model was used to assess the exposure-response relationship between BMI and serum lipid levels and dementia risk. Interactions and further classifications of BMI and serum lipid levels were further presented by bivariate surface models and decision-tree models. RESULTS: The joint effects of TC with BMI, TG with BMI, and LDL-C with BMI on the risk of incident dementia shared a similar pattern, different from their independent exposure-response curves. The joint effect of HDL-C with BMI showed an S-surface but without statistical significance. Participants with TC<5.4 mmol/L and BMI<21 kg/m2 (Hazard Ratio(HR) 1.93, 95% Confidence Interval (CI) 1.05-3.53), TC<5.4 mmol/L and BMI≥21 kg/m2 (HR 1.73, 95% CI 1.09-2.72), and TC≥5.4 mmol/L and BMI<21 kg/m2 (HR 4.02, 95% CI 2.10-7.71) were identified to have the increased risk of incident dementia compared to those with TC≥5.4 mmol/L and BMI≥21 kg/m2. Participants with TG<1.7 mmol/L and BMI<21 kg/m2 had an increased risk of incident dementia compared to those with TG≥1.7 mmol/L and BMI≥21 kg/m2 (HR 1.98, 95%CI 1.17-3.3). Participants with LDL-C≥3.3 mmol/L and BMI<21 kg/m2 were identified to have an increased risk of incident dementia compared to those with LDL-C≥3.3 mmol/L and BMI≥21 kg/m2 (HR 3.33, 95%CI 1.64-6.78). CONCLUSIONS: Our study showed that low BMI combined with low or high levels of serum lipids may increase the risk of dementia among older adults. This finding suggests the potential impacts of these two metabolic indexes on the risk of dementia.

Reliability and validity testing of the ASSIST functional performance index.

Reliability and validity testing of the ASSIST Functional Performance Index (AFPI) was conducted, focusing on persons with physical disabilities (PwPD). The AFPI was iteratively developed to assess persons' needs for Mainstream Smart Home Technologies (MSHT) as Assistive Technology (AT) and to measure the impact of a service delivery model for MSHT. The AFPI consists of 46 items organized by functional domains. A total of N = 22 PwPD completed the AFPI twice. The median response time between these two time points was four days. Test-retest reliability of overall scores was assessed using the Intraclass Correlation Coefficient model (ICC, 3.1). The weighted kappa coefficient was applied to conduct an item analysis, demonstrating moderate to substantial agreement in all but one of the items. During the second administration, validity was established by correlating the number of hours of assistance and total AFPI scores with the SCI-FI Self-Care and Basic Mobility Short Form Questionnaires. Results indicate that the AFPI demonstrates good to very good validity as an assessment tool and outcome measure in recommending and evaluating the impact of MSHT for PwPD. Future studies, including more participants and persons with cognitive and sensory disabilities, may further establish the clinical utility of the AFPI.

[Soybean isoflavones alleviate cerebral ischemia/reperfusion injury in rats by inhibiting ferroptosis and inflammatory cascade reaction].

OBJECTIVE: To explore the mechanism that mediates the effect of soybean isoflavones (SI) against cerebral ischemia/reperfusion (I/R) injury in light of the regulation of regional cerebral blood flow (rCBF), ferroptosis, inflammatory response and blood-brain barrier (BBB) permeability. METHODS: A total of 120 male SD rats were equally randomized into sham-operated group (Sham group), cerebral I/R injury group and SI pretreatment group (SI group). Focal cerebral I/R injury was induced in the latter two groups using a modified monofilament occlusion technique, and the intraoperative changes of real-time cerebral cortex blood flow were monitored using a laser Doppler flowmeter (LDF). The postoperative changes of cerebral pathological morphology and the ultrastructure of the neurons and the BBB were observed with optical and transmission electron microscopy. The neurological deficits of the rats was assessed, and the severities of cerebral infarction, brain edema and BBB disruption were quantified. The contents of Fe2+, GSH, MDA and MPO in the ischemic penumbra were determined with spectrophotometric tests. Serum levels of TNF-α and IL-1ßwere analyzed using ELISA, and the expressions of GPX4, MMP-9 and occludin around the lesion were detected with Western blotting and immunohistochemistry. RESULTS: The rCBF was sharply reduced in the rats in I/R group and SI group after successful insertion of the monofilament. Compared with those in Sham group, the rats in I/R group showed significantly increased neurological deficit scores, cerebral infarction volume, brain water content and Evans blue permeability (P < 0.01), decreased Fe2+ level, increased MDA level, decreased GSH content and GPX4 expression (P < 0.01), increased MPO content and serum levels of TNF-α and IL-1ß (P < 0.01), increased MMP-9 expression and lowered occludin expression (P < 0.01). All these changes were significantly ameliorated in rats pretreated with IS prior to I/R injury (P < 0.05 or 0.01). CONCLUSION: SI preconditioning reduces cerebral I/R injury in rats possibly by improving rCBF, inhibiting ferroptosis and inflammatory response and protecting the BBB.

Relating Translation Efficiency to Protein Networks Provides Evolutionary Insights in Shewanella and Its Implications for Extracellular Electron Transfer.

Shewanella species are well-known for their extracellular electron transfer (EET) capacity, by which these microorganisms can transfer the electrons from intracellular environment to extracellular space for the reduction of the extracellular insoluble electron acceptors. Using a time-stamped data for the paired protein-mRNA, we investigate the impact of differential translation on the EET process of Shewanella oneidensis MR-1. Firstly, differentially translated proteins when O2 levels are switched from high-O2 to low-O2 are identified by using a soft clustering method, 629 up-regulated translated proteins and 767 down-regulated translated proteins are considered to reflect the changes from inactivated to activated EET process. Then, we showed that the degrees of connectivity of differentially translated proteins were significantly larger than those of non-differentially translated proteins, and thereby these differentially translated proteins will be more important in the protein networks. After that, we networked these differentially translated proteins to construct the differentially translated sub-networks, and discussed the most important proteins that are involved in the EET process with the help of centralization analysis of these differentially translated networks. Furthermore, we also studied the differentially translated operonic genes. Taking together, this work searches the key proteins that potentially activated the EET process from a translational efficiency viewpoint.

[The relationship between Ruishou Ben'i Zenkushuu and the medical writings of the Zhu Zhengheng].

Ruishou Ben'i Zenkushuu(,The Nine Tenths of the the Differnetiation of Similar Syndromes) was compiled by Doctor Yuehu, a Japanese monk, in 1452. This book had important implications for the spread to Japan of Chinese medical ideas and theories by Li Dongyuan and Zhu Danxi. This paper analyzed the citation of Chinese medical books in Ruishou Ben'i Zenkushuu and found that the name of Zhu Danxi appeared frequently in this book.Based on the data from the sources of Danxi's medical ideas and theories cited in the book, this paper illuminates the close connection with the medicine ideas and theories of Danxi, and clarifies the story that Yuehu once studied Chinese medicine from Yu Tuan. Research on the sources of the ideas in Ruishou Ben'i Zenkushuu is helpful tracing back historically the spread of the ideas and theories of Danxi in Japan.

A two-in-one Janus NIR-II AIEgen with balanced absorption and emission for image-guided precision surgery.

Fluorescence imaging in the near-infrared II (NIR-II, 1000-1700 nm) region opens up new avenues for biological systems due to suppressed scattering and low autofluorescence at longer-wavelength photons. Nonetheless, the development of organic NIR-II fluorophores is still limited mainly due to the shortage of efficient molecular design strategy. Herein, we propose an approach of designing Janus NIR-II fluorophores by introducing electronic donors with distinct properties into one molecule. As a proof-of-concept, fluorescent dye 2 TT-m, oC6B with both twisted and planar electronic donors displayed balanced absorption and emission which were absent in its parent compound. The key design strategy for Janus molecule is that it combines the merits of intense absorption from planar architecture and high fluorescence quantum yield from twisted motif. The resulting 2 TT-m, oC6B nanoparticles exhibit a high molar absorptivity of 1.12 ⨯104 M-1 cm-1 at 808 nm and a NIR-II quantum yield of 3.7%, displaying a typical aggregation-induced emission (AIE) attribute. The highly bright and stable 2 TT-m, oC6B nanoparticles assured NIR-II image-guided cancer surgery to resect submillimeter tumor nodules. The present study may inspire further development of molecular design philosophy for highly bright NIR-II fluorophores for biomedical applications.

Hsa_circ_0007534 knockdown represses the development of colorectal cancer cells through regulating miR-613/SLC25A22 axis.

The article "Hsa_circ_0007534 knockdown represses the development of colorectal cancer cells through regulating miR-613/SLC25A22 axis, by D.-Y. Ding, D. Wang, Z.-B. Shu, published in Eur Rev Med Pharmacol Sci 2020; 24 (6): 3004-3022-DOI: 10.26355/eurrev_202003_20665-PMID: 32271418" has been withdrawn from the authors stating that "the findings are not reliable. The dosage was significantly low. The results can be misleading to many readers". The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20665.

Parity and the risk of incident dementia: a COSMIC study.

AIMS: To investigate the association between parity and the risk of incident dementia in women. METHODS: We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)). RESULTS: Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02-1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1-4 parities (HR = 1.30, 95% CI = 1.02-1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02-1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00-2.55), but the risk of AD was not significantly associated with parity. CONCLUSIONS: Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.

[Inner hair cells loss by carboplatin and the changes of cochlear compound action potential in chinchillas].

Objective: To measure the cochlear compound action potential (CAP) and the densities of hair cells (HCs) along the whole length of the basilar membrane (BM) in adult chinchillas. And to investigate the relationship between the severity of inner hair cells (IHCs) loss and the changes of CAP by using carboplatin-cochlear lesion model. Methods: Totally 18 chinchillas were recruited after ontological evaluation. They were randomly divided into three groups (with 6 subjects in each), A: control, B and C: legion groups treated with one or two shot(s) of carboplatin respectively (76 mg/kg in one shot, i.p., one-week interval between the two shots). Endpoint tests were performed 30 days after the carboplatin treatment in groups B and C, and matched time in group A. A sliver-ball electrode was placed into round window niche via hypotympanic approach in anesthetized chinchilla. CAP was measured in response to clicks and tone burst of 0.5, 1, 2, 4, 8, 16 kHz respectively under anesthesia. CAP amplitudes and thresholds were measured and compared across the groups. After the recording, the whole cochlea surface preparation was made and the HCs were stained in histochemistry against substrate of succinate dehydrogenase (SDH). Images were taken with high-resolution digital camera under light microscope and across the whole cochlea. The length of the basilar membrane (BM) and the number of both IHCs and OHCs were counted. The HC density was calculated as the number of HCs per 10% BM length. Results: The CAP thresholds were (7.1±2.6), (25.4±5.0), (24.6±5.4), (10.4±5.0), (0.4±1.4), (4.2±6.3) and (17.1±14.1) dB SPL (from 6 subjects in group A, n=12 ears) corresponding to stimuli of Click and 0.5, 1, 2, 4, 8, 16 kHz tone bursts respectively. The total number of cochlear HCs were measured as (8 936±643) (x±s) and the average length of the BMs was (17.73±1.012) mm from the six subjects in the group A (n=12 ears). The HC density was found to be varied slightly across the BM. There was no significant CAP threshold difference between the control (group A) and the group B, which received one shot of carboplatin. However, the maximal CAP amplitude was reduced by 40% in the group B and compared with group A. Correspondingly, approximately 40% loss of IHCs were seen. In contrast, a significant CAP threshold shift was seen in subjects receiving two shots of carboplatin (group C), which was accompanied by a loss of 90% IHCs. Conclusions: The CAP thresholds of adult chinchillas show typical open-V shape with the lowest values at 2, 4, and 8 kHz. IHC loss by carboplatin in certain degree is well correlated with CAP amplitude reduction, but does not change the threshold when inner hair cell loss reaches 40%, however, if inner hair cell loss exceeds 80%, the threshold shift of CAP will be inevitable.

Genomic Signature of Mismatch Repair Deficiency in Areca Nut-Related Oral Cancer.

Areca nut (AN) chewing contributes to an increase of oral squamous cell carcinoma (OSCC) cases in South and Southeast Asia; however, genomic events underlying the carcinogenesis process of AN-related OSCC remain unclear. Here, we comprehensively describe the genomic and transcriptome alterations of 113 Chinese OSCC patients (89 AN related and 24 AN negative) by whole-exome sequencing and RNA sequencing, and we compared the genomic differences between AN-related and AN-negative samples by integrating sequencing data of 325 OSCC patients from The Cancer Genome Atlas database and 50 from a published Taiwanese study. We identified 11 significantly mutated genes for OSCC, including 4 novel ones (ATG2A, WEE1, DST, and TSC2), of which WEE1 and ATG2A mutated with significantly higher rates in AN-related samples (P = 0.04 and P = 0.003, respectively). Mutational signature analysis revealed that AN-related OSCCs were specially characterized by the genomic signature of mismatch repair deficiency (dMMR), which could also predict the prognosis status of AN-related OSCC. In addition, an elevated PD-L1 expression was also observed in both AN-related patients (P = 3.71 × 10-11) and those with a high dMMR level (P = 1.99 × 10-4). Further differential expression analysis and in vitro experiments confirmed the role of dMMR in the development of OSCC induced by AN exposure. Taken together, this study first revealed the molecular profiles and highlighted the role of dMMR in AN-related OSCC among the Chinese population and identified that AN-related OSCC may represent a potential cohort for effective anti-PD-1/L1 immunotherapy.

Hsa_circ_0007534 knockdown represses the development of colorectal cancer cells through regulating miR-613/SLC25A22 axis.

OBJECTIVE: Colorectal cancer (CRC) is a common tumor around the world. Circular RNAs (circRNAs) have been reported to be related to the development of CRC. However, the detailed mechanism is complicated. This study aimed to reveal the functional mechanism of circ_0007534 in CRC. PATIENTS AND METHODS: Quantitative real time polymerase chain reation (qRT-PCR) and Western blot assay were performed to analyze gene expression. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay were carried out to determine cell proliferation ability. Furthermore, cell migratory and invasive abilities were assessed by transwell assay. Glycolytic metabolism was examined via the measurements of extracellular acidification rate (ECAR), glucose consumption, and lactate production. Also, the interaction between circ_0007534 or solute carrier family 25 member 22 (SLC25A22) and miR-613 was predicted and confirmed by starBase v2.0 and the Dual-Luciferase reporter assay, respectively. Mouse xenograft was performed to investigate the effect of circ_0007534 on tumor growth in vivo. RESULTS: Circ_0007534 and SLC25A22 levels were upregulated, and miR-613 level was downregulated in CRC tissues/cells. Circ_0007534 knockdown repressed CRC cell proliferation, colony formation, migration, invasion, and glycolysis. Interestingly, Circ_0007534 targeted miR-613, and miR-613 targeted SLC25A22. Circ_0007534 exerted its function by repressing miR-613 expression, and miR-613 exerted its function via inhibiting SLC25A22 expression. Also, Circ_0007534 repressed miR-613 expression to upregulate SLC25A22 level. Circ_0007534 depletion repressed tumor growth in vivo. CONCLUSIONS: We demonstrated that circ_0007534 knockdown suppressed the growth of CRC cells by regulating miR-613/SLC25A22 axis, providing potential target for the treatment of CRC.

Novel oral multifunctional antioxidant prevents noise-induced hearing loss and hair cell loss.

Oxidative stress is a major contributor to noise-induced hearing loss, the most common cause of hearing loss among military personnel and young adults. HK-2 is a potent, orally-active, multifunctional, redox-modulating drug that has been shown to protect against a wide range of neurological disorders with no observed side effects. HK-2 protected cochlear HEI-OC1 cells against various forms of experimentally-induced oxidative stressors similar to those observed during and after intense noise exposure. The mechanisms by which HK-2 protects cells is twofold, first by its ability to reduce oxidative stress generated by free radicals, and second, by its ability to complex biologically active transition metals such as Fe+2, thus reducing their availability to participate in the Fenton reaction where highly toxic hydroxyl radicals are generated. For the rat in vivo studies, HK-2 provided significant protection against noise-induced hearing loss and hair cell loss. Noise-induced hearing loss was induced by an 8-16 kHz octave band noises presented for 8 h/d for 21 days at an intensity of 95 dB SPL. In the Prevention study, HK-2 was administered orally beginning 5 days before the start of the noise and ending 10 days after the noise. Treatment with HK-2 dose-dependently reduced the amount of noise-induced hearing impairment, reflected in the cochlear compound action potential, and noise-induced hair cell loss. In a subsequent Rescue experiment in which HK-2 was administered for 10 days starting after the noise was turned off, HK-2 also significantly reduced the amount of hearing impairment, but the effect size was substantially less than in the Prevention studies. HK-2 alone did not adversely affect HEI-OC1 cell viability, nor did it cause any adverse changes in rat body weight, behavior, cochlear function or hair cell integrity. Thus, HK-2 is a novel, safe, orally-deliverable and highly effective otoprotective compound with considerable potential for preventing hearing loss from noise and other hearing disorders linked to excessive oxidative stress.

HMGA1-mediated miR-671-5p targets APC to promote metastasis of clear cell renal cell carcinoma through Wnt signaling.

This study aimed to investigate the effect of miR-671-5p on metastasis of clear cell renal cell carcinoma (ccRCC) and underlying mechanism involved. The migration and invasion of ccRCC cells were determined by transwell and boyden assays in vitro and in vivo. Genes mRNA and protein expression were detected by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. The target gene of miRNA was confirmed by luciferase reporter assays. Transcriptional regulation of miRNA by transcription factor was detected by chromatin immunoprecipitation assay (ChIP). The expression of miRNA in clinical specimens were detected by in situ hybridization (ISH). miR-671-5p promoted migration and invasion of ccRCC in vivo and in vitro. Moreover, miR-671-5p directly targeted APC to activate Wnt signaling, thus inducing the epithelial-mesenchymal transition (EMT) in ccRCC. Intriguingly, miR-671-5p expression was transcriptionally enhanced by HMGA1. Consistently, bioinformatics analysis suggested that HMGA1 was positively correlated with miR-671 expression, however, miR-671 was negatively correlated with APC. In situ hybridization analysis showed that miR-671-5p was upregulated in ccRCC compared with paracarcinoma and correlated with poor prognosis of ccRCC patients. In addition, univariate and multivariate analysis indicated that miR-671-5p expression was an independent prognostic factor for overall survival in ccRCC patients. Our data suggest that miR-671-5p is a tumor enhancer in regulating of ccRCC metastasis, and miR-671-5p may be utilized as a factor for the clinical diagnosis and prognosis of ccRCC.

[Role of a liver pathology standardized scoring system in the diagnosis of congenital biliary atresia and its relationship with prognosis].

Objective: To evaluate the diagnostic value of a histologic scoring system in congenital biliary atresia and its prognostic relevance. Methods: From January 2017 to June 2018 at Children's Hospital of Fudan University, 172 wedge liver biopsy specimens were obtained from infants with neonatal cholestasis [119 patients with congenital biliary atresia (CBA) and 53 patients with non-obstructive cholestasis as control]. A pathologist, single-blinded to the final diagnosis, made the histological diagnosis individually based on an 8-feature (portal ductal proliferation, bile duct reaction, bile plugs in portal ductules, liver fibrosis, edema in portal region, cholestasis, inflammatory cells infiltration in portal region, and ductal plate malformation), 21-point scoring system. Results: The main pathologic changes of biliary atresia were hepatocyte cholestasis, hyperplasia of bile ducts, fibrosis and infiltration of inflammatory cells in the portal area. There were significant difference in the degree of portal edema, bile duct hyperplasia and fibrosis between two groups (P<0.01). In addition, there were characteristic bile duct thrombosis in 97.5%(116/119) of the cases and abnormal development of bile duct plate in 9.2%(11/119) of the cases. Compared with non-CBA infant cholestasis group, the difference was statistically significant (P<0.05). The scoring system has high sensitivity, specificity (both 94.1%) and accuracy (94.3%) in the diagnosis of CBA. A score equal to or more than 11 points supported a diagnosis of CBA; whereas a score less than 11 points might suggest cholestasis. The degree of hepatic fibrosis and ductal plate malformation were related to prognosis. Conclusions: The liver pathology scoring system (8-feature, 21-point) is more accurate in diagnosing CBA than previous methods, which may guide the clinicopathological diagnosis. This histological scoring system also helps to assess the prognosis of CBA.