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The leaf beetle Ophraella communa LeSage (Coleoptera: Chrysomelidae) is an effective biological control agent of the common ragweed. Here, we assembled a chromosome-level genome of the O. communa by combining Illumina, Nanopore, and Hi-C sequencing technologies. The genome size of the final genome assembly is 733.1 Mb, encompassing 17 chromosomes, with an improved contig N50 of 7.05 Mb compared to the original version. Genome annotation reveals 25,873 protein-coding genes, with functional annotations available for 22,084 genes (85.35%). Non-coding sequence annotation identified 204 rRNAs, 626 tRNAs, and 1791 small RNAs. Repetitive elements occupy 414.41 Mb, constituting 57.76% of the genome. This high-quality genome is fundamental for advancing biological control strategies employing O. communa.

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Telangiectasias are the most frequent type of sequelae of infantile hemangiomas after involution. Few studies have reported the treatment of telangiectasias with 595-nm pulsed dye lasers. Therefore, the objective of this study was to assess the efficacy and safety of a 595-nm pulsed dye laser for treating residual telangiectasias following hemangioma involution. This is a retrospective case series that analyzes the medical records and reviews the charts of 22 patients who had undergone 595-nm pulsed dye laser treatment for residual telangiectasias. Pre- and post-treatment digital images were independently assessed, and the changes were scored to ascertain the efficacy of the treatment (0 = no change, 4 = complete improvement). Of the 22 patients, 59.1% experienced complete resolution of telangiectasias following treatment. No serious complications or side effects were reported. The observations indicate that the 595-nm pulsed dye laser is effective and safe for treating residual telangiectasias following hemangioma involution.

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The southwestern region of China is the largest exposed karst area in the world and serves as an important ecological security barrier for the upstream of Yangtze River and Pearl River. Different from the critical zone of non-karst areas, the epikarst, formed by an interwoven network of denudation pores, is the core area of karst critical zone. Water is the most active component that participates in internal material cycle and energy flow within the critical zone. We reviewed relevant research conducted in the southwestern region from three aspects: the characte-rization of critical zone structure, the hydrological processes of soil-epikarst system, and their model simulations. We further proposed potential research hotpots. The main approach involved multi-scale and multi-method integrated observations, as well as interdisciplinary collaboration. Precisely characterizing the eco-hydrological processes of the vegetation-soil-epikarst coupling system was a new trend in the future research. This review would provide scientific reference for further studies on hydrological processes in critical zones and regional hydrological water resource management in karst areas.

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OBJECTIVES: To evaluate the risk factors for postoperative complications in adolescents who undergo primary hypospadias repair and determine the time required for complication detection. METHODS: Our study included patients classified as Tanner stages three to five who underwent primary hypospadias repairs at our hospital from January 2015 to August 2022. The patients' baseline information, clinical characteristics, postoperative complications, and time to complication detection were collected. Cox regression analysis, ROC curves, Kaplan-Meier survival analyses, and the Mann-Whitney U test were used. RESULTS: The study comprised 143 patients, with a median age of 12.58 years. Postoperative complications were experienced by 66 patients. The length of the urethral defect was identified as an independent risk factor for postoperative complications. The ROC curve analysis identified 3 cm as the optimal cutoff value for the length of the urethral defect. The median time to complication detection was 30.5 days (IQR 23 to 209.25). 89.4% of the complications were identified within the first year. Patients with a urethral defect of <3 cm experienced a significantly longer time for the detection of urethral fistula compared to those with a urethral defect of ≥3 cm (p = 0.047). CONCLUSIONS: Our data indicate that adolescents with a urethral defect ≥3 cm have a higher risk of postoperative complications. Although most complications were identified within the first year, conducting long-term follow-ups for adolescents is recommended to identify potential subsequent complications that may arise from persistent urethral alterations.

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Objective To analyze the medication rules of Professor HUANG Feng for the treatment of low back pain using data mining methods.Methods The information of prescriptions for the effective cases of outpatients with low back pain treated by Professor HUANG Feng were collected and screened.Microsoft Excel 2019 was used to analyze the frequency of medication and the distribution of properties,flavors and meridian tropism of the drugs in the included prescription.IBM SPSS Modeler 18.0 was used for association rule analysis,and IBM Statistics 26.0 was used for cluster analysis.Results A total of 239 prescriptions and 75 Chinese medicines were included.There were 23 high-frequency Chinese medicines with the medication frequency being or over 20 times,and the top 10 Chinese medicines were Glycyrrhizae Radix et Rhizoma,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma,Zanthoxyli Radix,salt-processed Achyranthis Bidentatae Radix,Rehmanniae Radix,Dipsaci Radix,Coicis Semen,and Salviae Miltiorrhizae Radix et Rhizoma.The medicines were mainly warm in nature,and were sweet,bitter and pungent in flavor.Most of the drugs had the meridian tropism of liver,stomach and spleen meridians.Among the drug combinations obtained from association rule analysis with the top 20 highest support,vinegar-processed Corydalis Rhizoma,Cibotii Rhizoma,Atractylodis Macrocephalae Rhizoma and Zanthoxyli Radix were the core drugs.Cluster analysis yielded 6 clustering combinations.Conclusion For the treatment of low back pain,Professor HUANG Feng follows the principle of"treatment adapting to the climate,individuality,and environment"and"treating the root cause of the disease",usually adopts the drugs for activating blood,moving qi and relieving pain,nourishing the liver and kidney,and also uses the medicines for replenishing qi and strengthening the spleen.The ideas of HUANG Feng for the treatment of low back pain can be used as a reference for the clinical treatment.

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The fruit fly Zeugodacus tau (Diptera: Tephritidae) is a major pest of melons and other cucurbits in Southeast Asia. In this study, we used Illumina, Nanopore, and Hi-C sequencing technologies to assemble a reference genome of Z. tau at the chromosomal level. The assembled genome was 421.79 Mb and consisted of six chromosomes (one X-chromosome + five autosomes). The contig N50 was 4.23 Mb. We identified 20,922 protein-coding genes, of which 17,251 (82.45%) were functionally annotated. Additionally, we found 247 rRNAs, 435 tRNAs, 67 small nuclear RNAs, and 829 small RNAs in the genome. Repetitive elements accounted for 55.30 Mb (13.15%) of the genome. This high-quality genome assembly is valuable for evolutionary and genetic studies of Z. tau and its relative species.

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Background: Surgical site infections (SSIs) that occur after hypospadias repair frequently result in incision healing complications, especially during puberty. This study aimed to evaluate the efficacy of twice-daily pre-operative skin preparation using body wash and povidone-iodine within 48 hours before hypospadias repair with regard to infection rates in adolescents. Patients and Methods: Prospective recruitment included patients in Tanner stages 3 to 5 undergoing hypospadias repair from January 2015 to January 2021. The experimental group comprised patients who performed twice-daily skin preparation with body wash and povidone-iodine within 48 hours before surgery. Surgeons selected either 0.5% or 5% povidone-iodine for skin preparation. The control group comprised a retrospective cohort of hypospadias repair conducted in the preceding five years, where patients performed pre-surgery evening showers using a body wash. Complications were collected over a six-month follow-up period. Results: The study included 90 patients in the 0.5% povidone-iodine group, 92 patients in the 5% povidone-iodine group, and 84 patients in the control group. Differences were observed among the groups in terms of SSI (p = 0.030) and urethral fistula (p = 0.019). In post hoc tests, only the 5% povidone-iodine group demonstrated a diminished incidence of SSI (p = 0.009) and urethral fistula (p = 0.005) in comparison to the control group. Conclusions: Using body wash and 5% povidone-iodine for skin preparation was associated with a reduction in the incidence of SSI and urethral fistula following hypospadias repair in adolescents and may be considered to improve outcomes.

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In developing low-temperature cofired ceramic (LTCC) technology for high-density packaging or advanced packaged electronics, matching the coefficient of thermal expansion (CTE) among the packaged components is a critical challenge to improve reliability. The CTEs of solders and organic laminates are usually larger than 16.0 ppm of °C1-, while most low-permittivity (εr) dielectric ceramics have CTEs of less than 10.0 ppm °C1-. Therefore, a good CTE match between organic laminates and dielectric ceramics is required for further LTCC applications. In this paper, we propose a high-CTE BaSO4-BaF2 LTCC as a potential solution for high-reliability packaged electronics. The BaSO4-BaF2 ceramics have the advantages of a wide low-temperature sintering range (650-850 °C), low loss, temperature stability, and Ag compatibility, ensuring excellent performance in LTCC technology. The 95 wt %BaSO4-5 wt %BaF2 ceramic has a εr of 9.1, a Q × f of 40,100 GHz @11.03 GHz (Q = 1/tan δ), a temperature coefficient of the resonant frequency of -11.2 ppm °C1-, a CTE of +21.8 ppm °C1-, and a thermal conductivity of 1.3 W mK-1 when sintered at 750 °C. Furthermore, a dielectric resonant antenna using BaSO4-BaF2 ceramics, a typically packaged component of LTCC and laminate, was designed and used to verify the excellent performance by a gain of 6.0 dBi at a central frequency of 8.97 GHz and a high radiation efficiency of 90% over a bandwidth of 760 MHz. Good match and low thermal stress were found in the packaged components of BaSO4-BaF2 ceramics, organic laminates, and Sn-based solders by finite element analysis, proving the potential of this LTCC for high-reliability packaged electronics.

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PURPOSE: To establish a parameter-based grading system for evaluating bladder trabeculation (BT). MATERIALS AND METHODS: A retrospective analysis was conducted on children diagnosed with posterior urethral valve (PUV) or neurogenic bladder (NB) who underwent voiding cystourethrogram (VCUG), urodynamic testing, and urological ultrasonography between January 2016 and October 2022. Cases involving urologic surgery, secondary bladder pathology, and an interval of more than 12 months between examinations were excluded. A parameter named Bladder Dispersion (BD) was calculated through fluoroscopic images, and the grading system was developed as follows: BD < 40 (Grade 0), 40 ≤ BD < 60 (Grade 1), 60 ≤ BD < 90 (Grade 2), BD ≥ 90 (Grade 3). Grades 0-1 were classified as low-risk group, while grades 2-3 were classified as high-risk group. Analysis of variance, Kruskal-Wallis test, and Chi-square test were performed to compare urodynamic results and complications across different grades and groups. RESULTS: A total of 74 patients were eligible to participate, which included 46 boys (62.2%) and 28 girls (37.8%), the mean age was 75.18 ± 48.39 months. Among them, 11 (14.9%) were PUV, 50 (67.6%) were NB, and 13 (17.5%) were PUV and NB. Significant differences were observed in maximum detrusor pressure, post-void residual urine ratio, and compliance among grades 0-3. Severe hydronephrosis and histories of urinary tract infection were more prevalent in the high-risk group. CONCLUSION: A reliable grading system with objective standards was proposed which could aid in the assessment of BT severity.

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BACKGROUND: Radical resection remains an effective strategy for patients with hepatocellular carcinoma (HCC). Unfortunately, the postoperative early recurrence (recurrence within 2 years) rate is still high. AIM: To develop a radiomics model based on preoperative contrast-enhanced computed tomography (CECT) to evaluate early recurrence in HCC patients with a single tumour. METHODS: We enrolled a total of 402 HCC patients from two centres who were diagnosed with a single tumour and underwent radical resection. First, the features from the portal venous and arterial phases of CECT were extracted based on the region of interest, and the early recurrence-related radiomics features were selected via the least absolute shrinkage and selection operator proportional hazards model (LASSO Cox) to determine radiomics scores for each patient. Then, the clinicopathologic data were combined to develop a model to predict early recurrence by Cox regression. Finally, we evaluated the prediction performance of this model by multiple methods. RESULTS: A total of 1915 radiomics features were extracted from CECT images, and 31 of them were used to determine the radiomics scores, which showed a significant difference between the early recurrence and nonearly recurrence groups. Univariate and multivariate Cox regression analyses showed that radiomics scores and serum alpha-fetoprotein were independent indicators, and they were used to develop a combined model to predict early recurrence. The area under the receiver operating characteristic curve values for the training and validation cohorts were 0.77 and 0.74, respectively, while the C-indices were 0.712 and 0.674, respectively. The calibration curves and decision curve analysis showed satisfactory accuracy and clinical utilities. Kaplan-Meier curves based on recurrence-free survival and overall survival showed significant differences. CONCLUSION: The preoperative radiomics model was shown to be effective for predicting early recurrence among HCC patients with a single tumour.

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BACKGROUND: Serum alanine aminotransferase (ALT) levels are often considered a marker to evaluate liver disease and its severity. AIM: To investigate the association between ALT levels and all-cause and cause-specific mortality in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: The Third National Health and Nutrition Examination Survey (NHANES-III) from 1988 to 1994 and NHANES-III-related mortality data from 2019 onward were used to obtain the necessary data for the study. NAFLD was defined as hepatic steatosis, as diagnosed by ultrasound, with no other liver diseases. ALT levels were categorized into four groups according to the different recommended upper limits of normal (ULN) in men and women: < 0.5 ULN, 0.5-1 ULN, 1-2 ULN, and ≥ 2 ULN. The hazard ratios for all-cause mortality and cause-specific mortality were analyzed using the Cox proportional hazard model. RESULTS: Multivariate logistic regression analysis demonstrated that the odds ratio of NAFLD correlated positively with increased serum ALT levels. In patients with NAFLD, all-cause mortality and cardiovascular mortality were the highest when ALT was < 0.5 ULN, yet cancer-related mortality was the highest when ALT was ≥ 2 ULN. The same results could be found in both men and women. Univariate analysis showed that severe NAFLD with normal ALT levels had the highest all-cause and cause-specific mortality, but the difference was not statistically significant after adjustment for age and multivariate factors. CONCLUSION: The risk of NAFLD was positively correlated with ALT level, but all-cause and cardiovascular mortality were the highest when ALT was < 0.5 ULN. Regardless of the severity of NAFLD, normal or lower ALT levels were associated with higher mortality than elevated ALT levels. Clinicians should be aware that high ALT levels indicate liver injury, but low ALT levels are associated with a higher risk of death.

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Background: Inconsistent relationships have been shown between cigarette smoking and hypospadias in offspring. The purpose of this study was to summarize epidemiological evidence to evaluate the relationship between parental smoking and the risk of hypospadias. Methods: Up until October 2022, PubMed, EMBASE, Web of Science, and the Cochrane Library were systematically searched for qualified research. The summary RRs and 95% CIs were calculated using either a fixed-effects or a random-effects model. There were subgroup analyses undertaken to identify potential sources of heterogeneity. Results: 44 studies with 16,637,830 participants were included in our meta-analysis. Overall, maternal active smoking [risk ratio (RR) = 0.94; 95% confidence interval (CI): 0.90-0.99; P < 0.01] was significantly associated with the risk of hypospadias. And neither paternal smoking (RR = 1.00; 95% CI: 0.86-1.15) nor maternal passive smoking (RR = 0.91; 95% CI: 0.60-1.23) was associated with the risk of hypospadias. Conclusion: Our study discovered an association between maternal active smoking and a decreased risk of hypospadias, which may be due to the effect of smoking on androgen. However, as numerous studies have proved that cigarette smoking during pregnancy increases the risk of overall birth abnormalities in offspring, quitting cigarettes before pregnancy positively influences the health of offspring and should be advocated worldwide. Systematic review registration: [www.crd.york.ac.uk/prospero], identifier [CRD42022319378].

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The olfactory system plays a key role in various insect behaviors, and odorant-binding proteins participate in the first step of the olfactory process. Ophraella communa Lesage is an oligophagous phytophagous insect that is a specific biological control agent for Ambrosia artemisiifolia L. The leaf beetle must identify and locate A. artemisiifolia through olfaction; however, its odorant-binding protein (OBP) function has not yet been reported. In this study, OcomOBP7 was cloned, and its tissue expression profile and binding ability were analyzed using RT-qPCR and fluorescence binding assays, respectively. Sequence analysis demonstrated that OcomOBP7 belongs to the classical OBP family. The RT-qPCR results showed that OcomOBP7 was specifically expressed in the antennae, indicating that OcomOBP7 may be involved in chemical communication. The fluorescence binding assay showed that OcomOBP7 has an extensive binding ability to alkenes. The electroantennography experiments showed that O. communa antennal response to α-pinene and ocimene decreased significantly after interference because the two odors specifically bound to OcomOBP7. In summary, α-pinene and ocimene are odorant ligands corresponding to OcomOBP7, indicating that OcomOBP7 is involved in the chemical recognition of A. artemisiifolia. Our study lays a theoretical foundation for research into O. communa attractants, which is helpful for the better biological control of A. artemisiifolia by O. communa.

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Conductive hydrogel (CH) as flexible electrophysiology interface has become the new trend of bioelectronics, but still challenging in synergizing the biocompatibility, mechanics and comprehensive electrical performance. Hyaluronic acid (HA), featured with abundant active sites for personalized-modification and well-known biocompatibility, is one of the alterative candidates. The obstacle lies in the unstable conductivity from the ionic conduction, and the electronic conduction by embedding conductive nanoparticles (NPs) is likely to result in inhomogeneous CH with poor stretchability and discontinuous conductive network. Herein, inspired by catechol chemistry, dopamine (DA)-modified HA was homogeneously composited with DA-modified poly (3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS, named PP), to produce particle-free conductive hydrogel (HA-DA-PP). The DA-introduced multiple bondings in HA network and PP molecules brought aqueous conductive PP into HA hydrogel to form a homogeneous crosslinking network, imparted the flexible stretchability. By accurately regulation, HA-DA-PP achieved high stretchability with large tensile deformation (over 470 %) in the category of natural polymer-based hydrogels. Moreover, the interaction between DA and PP (conformational transition and charge transfer) could effectively enhance the hydrogel's conductivity. Consequently, HA-DA-PP hydrogel showed high sensibility to human movement, epidermal and in vivo electrophysiological signals monitoring. Overall, DA-mediated multiple bonding is a powerful strategy for constructing CH with high performance for bioelectronics.

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In the era of antiviral therapy, the main goal of treatment has shifted from the persistent inhibition of hepatitis B virus (HBV) replication to the pursuit of serological clearance of HBs surface antigen (HBsAg). Based on the life cycle of HBV, HBsAg originates from covalently closed circular DNA (cccDNA) and integrated HBV DNA, thus reflecting their transcriptional activity. Complete HBsAg loss may mean elimination or persistent inactivity of the HBV genome including cccDNA and integrated HBV DNA. HBsAg loss improves the recovery of abnormal immune function, which in turn, may further promote the clearance of residual viruses. Combined with functional cure and the great improvement of clinical outcomes, the continuous seroclearance of high-sensitivity quantitative HBsAg may represent the complete cure of chronic hepatitis B (CHB). For many other risk factors besides HBV itself, patients with HBsAg loss still need regular monitoring. In this review, we summarized the evolution of CHB treatment, the origin of serum HBsAg, the pattern of HBsAg seroclearance, and the effect of HBsAg loss on immune function and disease outcomes. In addition, we discuss the significance of high-sensitivity HBsAg detection and its possibility as a surrogate of complete cure.

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INTRODUCTION: As a common autoimmune disease with the characteristic of early complication, primary biliary cholangitis (PBC) leads to an increasing number of mortalities among people with end-stage liver disease (ESLD) waiting for liver transplantation. Ursodeoxycholic acid (UDCA) is the only approved first-line medicine for PBC, and a good response to treatment could acquire an ideal prognosis. Patients with poor UDCA response usually have more adverse outcomes and worse survival, therefore, the management of this group become a major consideration. AREAS COVERED: Due to the complexity of race and environment for PBC, different criteria for UDCA response exhibit various predictive performances. Factors affecting UDCA response conditions include gender, age, ethnicity, serum indicators, auto-antibodies, and autoimmune comorbidities, while no agreement has been reached. In this review, we mainly focus on cellular senescence, immune-mediated damage, and vitamin D deficiency as possible mechanisms for UDCA non-responders. EXPERT OPINION: The pathogenesis of PBC has yet to be clarified. Immunology-related mechanisms and therapy targets ought to be the main effort made for further study. Irrespective of the response condition, UDCA is recommended for routine administration in all PBC patients without contraindication. Ongoing clinical trials of second-line and additional therapy exhibit promising prospects.

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The chemical components of Xin'an famous prescription Ershen Zhenwu Decoction (ESZWD) are still unclear. The results showed that ESZWD could significantly reduce left ventricular end diastolic diameter, decrease N-terminal pro-brain natriuretic peptide (NT-proBNP), angiotensinII, aldosterone, reactive oxygen species, and malondialdehyde, increase serum superoxide dismutase, while had no significant effect on inflammatory factors. Ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) analysis detected 30 prototype components in model rats' serum, mainly including alkaloids, saponins, terpenoids, tanshinones, phenols. UPLC-MS/MS successfully detected the pharmacokinetic parameters of four components, and correlation analysis shows that there are negative correlations between four compounds and serum NT-proBNP. Thirty components of ESZWD may play a therapeutic role in chronic heart failure with heart-kidney Yang deficiency (CHF-HKYd) by improving myocardial injury, reducing oxidative stress levels, and inhibiting activation of the RAAS system in rats. Salsolinol, aconitine, paeoniflorin, and miltrione are equipped with potential characteristics as pharmacodynamic substances for ESZWD in treating CHF-HKYd. Additionally, the constituents of ESZWD in CHF-HKYd rats are different from normal rats, which provided a reference for the selection of subjects for further study.

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BACKGROUND: Noninvasive, practical, and convenient means of detection for the prediction of liver fibrosis and cirrhosis in China are greatly needed. AIM: To develop a precise noninvasive test to stage liver fibrosis and cirrhosis. METHODS: With liver biopsy as the gold standard, we established a new index, [alkaline phosphatase (U/L) + gamma-glutamyl transpeptidase (U/L)/platelet (109/L) (AGPR)], to predict liver fibrosis and cirrhosis. In addition, we compared the area under the receiver operating characteristic curve (AUROC) of AGPR, gamma-glutamyl transpeptidase to platelet ratio, aspartate transaminase to platelet ratio index, and FIB-4 and evaluated the accuracy of these routine laboratory indices in predicting liver fibrosis and cirrhosis. RESULTS: Correlation analysis revealed a significant positive correlation between AGPR and liver fibrosis stage (P < 0.001). In the training cohort, the AUROC of AGPR was 0.83 (95%CI: 0.78-0.87) for predicting fibrosis (≥ F2), 0.84 (95%CI: 0.79-0.88) for predicting extensive fibrosis (≥ F3), and 0.87 (95%CI: 0.83-0.91) for predicting cirrhosis (F4). In the validation cohort, the AUROCs of AGPR to predict ≥ F2, ≥ F3 and F4 were 0.83 (95%CI: 0.77-0.88), 0.83 (95%CI: 0.77-0.89), and 0.84 (95%CI: 0.78-0.89), respectively. CONCLUSION: The AGPR index should become a new, simple, accurate, and noninvasive marker to predict liver fibrosis and cirrhosis in chronic hepatitis B patients.

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BACKGROUND: Osteoarthritis (OA), caused by the destruction of joint cartilage, is the most prevalent form of arthritis, causing pain and stiffness in joints among millions of patients worldwide. Increasing evidence suggests that non-coding RNAs, including circular RNAs, play important roles in the pathogenesis of OA, but the precise signaling pathway is still unclear. METHODS: To study OA, we established a mouse model by the destabilized medial meniscus (DMM) surgery and used IL-1ß stimulated human cell line C28/I2 as an in vitro study. To further study the role of circSPI1_005 in regulating cell proliferation and apoptosis, EdU staining and FACS-based (fluorescence-activated cell sorting) apoptosis examination were performed after the manipulation of the expression of circSPI1_005. Also, bioinformatics predictions were conducted to analyze the downstream microRNAs of circSPI1_005 and the protein regulated by circSPI1_005. The luciferase assay and the RNA immunoprecipitation (RIP) assay were used to confirm the binding between circSPI1_005 and the predicted microRNA. To verify the role of circSPI1_005 in regulating OA in vivo, we also over-expressed circSPI1_005 by injecting AAV into previously injured knees to improve the OA symptoms. RESULTS: In this study, we found that circSPI1_005 was significantly down-regulated in IL-1ß treated chondrocyte cell lines and cartilage tissues of the OA mouse model. Overexpression of circSPI1_005 ameliorated OA by increasing proliferation and inhibiting apoptosis, and knockdown of circSPI1_005 in chondrocytes mimicked OA phenotypes. Bioinformatics study showed circSPI1_005 could sponge to miR-370-3p, and mechanistic studies confirmed the functional binding between circSPI1_005 and miR-370-3p. Furthermore, we conducted a TargetScan analysis and found that MAP3K9 (mitogen-activated protein kinase kinase kinase 9) could be the downstream protein effector. The expression level of MAP3K9 was regulated by miR-370-3p and overexpression of MAP3K9 could efficiently ameliorate OA. Also, we over-expressed circSPI1_005 in vivo and found that the cartilage surface in the OA mouse model was improved with overexpression of circSPI1_005. CONCLUSIONS: Collectively, circSPI1_005 could sponge to miR-370-3p to regulate the expression of MAP3K9, ameliorating the progression of osteoarthritis.

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AIM: To explore the efficacy of conbercept after switching from bevacizumab/ranibizumab in eyes of central retinal vein occlusion (CRVO) through optical coherence tomography angiography (OCTA). METHODS: Patients with prior treatment of a minimum of three consecutive intravitreal injections of either bevacizumab or ranibizumab, followed by injection of conbercept, were recruited. The minimal follow-up period after switching was 12mo. Central retinal thickness (CRT), best-corrected visual acuity (BCVA), the interval of injections was reviewed. Perfusion density (PD) and vascular length density (VLD) of superficial and deep capillary plexus were acquired from OCTA images before and after switching. RESULTS: Twenty-four eyes were included. CRT significantly decreased from 460.71±153.23 µm (before switching) to 283.92±38.27 µm at the end of follow-up (P<0.001). However, BCVA gained to some extent (from 0.98±0.33 to 0.76±0.42 logMAR) but the difference was not significant (P=0.070). After switching to conbercept the injection interval extended from 5.2±2.3wk to 8.3±3.9wk (P=0.012). At the end of follow-up, PD of deep retinal layer decreased significantly compared with before switching (from 34.62%±5.27% to 33.26%±5.82%, P=0.016), similar result was found in VLD of deep retinal layer but not in PD or VLD in superficial layer. CONCLUSION: In cases of refractory macular edema secondary to CRVO, switching to conbercept improves macular thickness and extends interval of injection. Retinal microvasculature cannot improve with treatment of conbercept.