Inhibition of KIF20A enhances the immunotherapeutic effect of hepatocellular carcinoma by enhancing c-Myc ubiquitination.

Immune therapy has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients, yet its efficacy remains limited, underscoring the urgency to identify new therapeutic targets and biomarkers. Here, we investigated the pathological and physiological roles of KIF20A and assess its potential in enhancing HCC treatment efficacy when combined with PD-1 inhibitors. We initially assess KIF20A's oncogenic function using liver-specific KIF20A knockout (Kif20a CKO) mouse models and orthotopic xenografts. Subsequently, we establish a regulatory axis involving KIF20A, FBXW7, and c-Myc, validated through construction of c-Myc splicing mutants. Large-scale clinical immunohistochemistry (IHC) analyses confirm the pathological relevance of the KIF20A-FBXW7-c-Myc axis in HCC. We demonstrate that KIF20A overexpression correlates with poor prognosis in HCC by competitively inhibiting FBXW7-mediated degradation of c-Myc, thereby promoting glycolysis and enhancing tumor proliferation. Conversely, KIF20A downregulation suppresses these effects, impairing tumor growth through c-Myc downregulation. Notably, KIF20A inhibition attenuates c-Myc-induced MMR expression, associated with improved prognosis in HCC patients receiving PD-1 inhibitor therapy. Furthermore, in Kif20a CKO HCC mouse models, we observe synergistic effects between Kif20a knockout and anti-PD-1 antibodies, significantly enhancing immunotherapeutic efficacy against HCC. Our findings suggest that targeting the KIF20A-c-Myc axis could identify HCC patients likely to benefit from anti-PD-1 therapy. In conclusion, we propose that combining KIF20A inhibitors with anti-PD-1 treatment represents a promising therapeutic strategy for HCC, offering new avenues for clinical development and patient stratification.

Skeletal muscle cystathionine γ-lyase deficiency promotes obesity and insulin resistance and results in hyperglycemia and skeletal muscle injury upon HFD in mice.

OBJECTIVES: The objective of this study was to investigate whether skeletal muscle cystathionine γ-lyase (CTH) contributes to high-fat diet (HFD)-induced metabolic disorders using skeletal muscle Cth knockout (CthΔskm) mice. METHODS: The CthΔskm mice and littermate Cth-floxed (Cthf/f) mice were fed with either HFD or chow diet for 13 weeks. Metabolomics and transcriptome analysis were used to assess the impact of CTH deficiency in skeletal muscle. RESULTS: Metabolomics coupled with transcriptome showed that CthΔskm mice displayed impaired energy metabolism and some signaling pathways linked to insulin resistance (IR) in skeletal muscle although the mice had normal insulin sensitivity. HFD led to reduced CTH expression and impaired energy metabolism in skeletal muscle in Cthf/f mice. CTH deficiency and HFD had some common pathways enriched in the aspects of amino acid metabolism, carbon metabolism, and fatty acid metabolism. CthΔskm+HFD mice exhibited increased body weight gain, fasting blood glucose, plasma insulin, and IR, and reduced glucose transporter 4 and CD36 expression in skeletal muscle compared to Cthf/f+HFD mice. Impaired mitochondria and irregular arrangement in myofilament occurred in CthΔskm+HFD mice. Omics analysis showed differential pathways enriched between CthΔskm mice and Cthf/f mice upon HFD. More severity in impaired energy metabolism, reduced AMPK signaling, and increased oxidative stress and ferroptosis occurred in CthΔskm+HFD mice compared to Cthf/f+HFD mice. DISCUSSION: Our results indicate that skeletal muscle CTH expression dysregulation contributes to metabolism disorders upon HFD.

Renal cell carcinoma in an adult-onset ESRD patient with nephronophthisis harboring NPHP3 deletion: A case report.

Background: Nephronophthisis (NPHP) is a rare autosomal recessive inherited tubulointerstitial nephropathy, the most prevalent genetic cause of end-stage renal disease (ESRD) in children. Convincing evidence indicated that the overall prevalence of NPHP in adult-onset ESRD is very likely to be an underestimation. Therefore, understanding the genetic background and clinicopathologic features of adult-onset NPHP is warranted. Case presentation: we reported one intriguing case with concurrent NPHP3 c.2694-2_2694-1delAG (splicing) variant and c.1082C > G (p.S361C) variant. A 48-year-old male was admitted to our hospital, complained about renal dysfunction for 10 years, and found right renal space-occupying lesion for 1 week. One of the most interesting clinical features is adult-onset ESRD, which differs from previous cases. Another discovery of this study is that the NPHP harboring NPHP3 deletion may be associated with clear cell renal cell carcinoma. Conclusion: In conclusion, we report two mutations in the NPHP3 gene that cause NPHP with adult-onset ESRD and renal clear cell carcinoma in a Chinese family, enriching the clinical features of NPHP.

[Effect of recombinant human thrombopoietin on platelets in rats with D-galactosamine salt-induced acute liver failure].

OBJECTIVE: To evaluate the effects of recombinant human thrombopoietin (rhTPO) on platelet count (PLT) and liver function in acute liver failure (ALF) rats by observing the dynamic changes of PLT, thrombopoietin (TPO) and liver function during ALF. METHODS: Twenty-four male Sprague-Dawley (SD) rats were divided into model group, TPO group and interleukin-11 (IL-11) group using a random number table method, with eight rats in each group. All rats were intraperitoneally injected with D-galactosamine (D-GalN, 1 500 mg/kg, dosed within 72 hours) to induce the ALF model. After modeling, rats in TPO group was received subcutaneous injection of 15 µg/kg of rhTPO for 5 days, and rats in IL-11 group was received subcutaneous injection of 0.45 mg/kg of IL-11 for 5 days. Venous blood samples were collected before and at 1, 3, 5, 7 and 12 days after molding for whole blood cell detection. The level of TPO in serum was detected by enzyme-linked immunosorbent assay (ELISA). Liver function indexes including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and albumin (ALB) were measured before and at 1, 3 and 5 days after modeling. The rats were sacrificed 12 days after the modeling, and the pathological changes of liver tissue were observed by hematoxylin-eosin (HE) staining. RESULTS: Two rats in each group died within 24-48 hours after modeling. HE staining showed that all three groups of ALF rats showed large flake necrosis of hepatocytes, disorder of hepatic lobular structure, mesh scaffold collapse, hepatic sinus congestion and hemorrhage, and flake infiltration of inflammatory cells on day 12 after modeling. The levels of serum ALT, AST and TBil of rats in each group were significantly increased 1 day after modeling and then decreased. The level of ALB decreased significantly on the first day after modeling and then increased, but there was no significant difference in the trend of liver function indexes among the three groups. PLT in the three groups decreased rapidly on day 1 after modeling, and then recovered gradually with the improvement of liver function. The PLT of the TPO group rose to the peak value 7 days after molding and was significantly higher than that of the model group [PLT (×109/L): 1 673.3±347.5 vs. 855.3±447.0, P < 0.05], while there was no significant difference between the IL-11 group and the model group [PLT (×109/L): 1 350.3±386.6 vs. 855.3±447.0, P > 0.05]. The level of serum TPO of the three groups increased significantly on day 1 after modeling, then decreased, and dropped to the lowest value on day 5, but there was no significant difference in the trend of serum TPO level among the three groups. CONCLUSIONS: PLT in ALF rats decreased rapidly in the early stage and recovered gradually with the improvement of liver function, and the serum TPO level increased first and then decreased. Injection of rhTPO can significantly increase PLT in ALF rats, but has no significant effect on liver function and survival rate.

Deciphering m6A signatures in hepatocellular carcinoma: Single-cell insights, immune landscape, and the protective role of IGFBP3.

RNA m6 methyladenosine (m6A) modifications impact tumor biology and immune processes, particularly in hepatocellular malignant tumors. Using a consensus clustering algorithm on 371 hepatocellular carcinoma (HCC) samples, we identified three m6A-modified subtypes and correlated them with positive tumor microenvironment (TME) markers for distinct immune phenotypes. Stratifying patients based on m6A scores revealed a low presentation group with better immune penetration, lower tumor mutation load, and increased expression of immune checkpoint markers like CTLA-4 and PD-1, suggesting enhanced responsiveness to immunization therapy. A machine-learning model of 23 m6A genes was constructed. Single-cell analysis revealed a surprising enrichment of IGFBP3 in astrocytes, prompting the exploration of associated signaling pathways. Experimental verification shows that IGFBP3 is significantly enhanced in normal tissues, while immunohistochemical analysis shows that its expression is lower in tumor tissues, indicating its protective effect in HCC and a good prognosis. Importantly, high IGFBP3 expression is associated with better outcomes in patients receiving immunotherapy. Moreover, cytotoxic T lymphocyte (CTL) experiments have confirmed that high expression of IGFBP3 is associated with stronger T cell-killing ability. In summary, the comprehensive evaluation of m6A modification, immune characteristics, and single-cell analysis in this study not only revealed the TME of HCC but also made significant contributions to the progress of personalized HCC immunotherapy targeting IGFBP3. This study provides a solid theoretical foundation for clinical translation and emphasizes its potential impact on developing effective treatment strategies.

Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy.

Four major studies (Checkmate577, Keynote-590, Checkmate649 and Attraction-4) of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy, represented by anti-programmed death protein (PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer, from the aspects of proof of concept, long-term survival, overall survival rate and progression-free survival. For unresectable or inoperable nonmetastatic esophageal cancer, concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines. Because its curative effect is still not ideal, it is necessary to explore radical radiotherapy and chemotherapy in the future, and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1. This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

Achieving Complete Tumor Clearance: A Minimalist Manganese Hydrogel for Magnetic Resonance Imaging-Guided Synergetic Microwave Ablation and Chemodynamic Therapy.

The combination of microwave ablation (MWA) and chemodynamic therapy (CDT) presents a promising strategy for complete eradication of residual tumor after MWA. However, it remains challenging and urgent to develop a facile, biocompatible, and imaging-guided platform for the achievement of this goal. Herein, a minimalist manganese hydrogel (ALG-Mn hydrogel) is proposed for synergistic MWA and CDT to completely eradicate tumor in vivo. The ALG-Mn hydrogel is prepared using a simple mixing method and exhibits excellent syringeability, remarkable microwave sensitivity, and potent Fenton-like activity. By assisting in MWA procedures, the ALG-Mn hydrogel enables both elimination of primary tumor mass through enhanced MWA efficacy and eradication of potential residual tumor tissues via robust CDT. This approach achieves complete tumor clearance without additional drug loading. Furthermore, the paramagnetic Mn2+ component allows real-time dynamic visualization of the ALG-Mn hydrogel at the tumor site via magnetic resonance imaging. To the best of knowledge, the proposed ALG-Mn hydrogel represents the minimalist biocompatible platform for imaging-guided synergistic MWA and CDT toward achieving complete tumor clearance.

Cytokine profiles and virological markers highlight distinctive immune statuses, and effectivenesses and limitations of NAs across different courses of chronic HBV infection.

PURPOSE: The characteristics of cytokine/chemokine(CK) profiles across different courses of chronic hepatitis B virus infection and the effects of NAs antiviral therapy on cytokine profiles remain unclear. METHODS: This report provides evidence from 383 patients with chronic HBV infection. The Luminex multiple cytokine detection technology was used to detect CK profiles. The predictive power of CKs across course of disease was assessedusing univariate analyses and with receiver operating characteristic (ROC) curves. RESULTS: Compared to healthy control (HC), expression levels of interleukin 6 (IL)-6, IL-8, IL-21, matrix metalloproteinases (MMP)-2 and tumor necrosis factor receptor (TNFR)-1 showed a significant increasing trend during chronic HBV infection. IL-23 and IL-33 increased respectively in chronic hepatitis B patients (CHB). interferon (IFN)-gamma and TNF-α changed significantly only in liver cirrhosis (LC) patients. Whereas, myeloid-related markers decreased dramatically in those with hepatocellular carcinoma (HCC). The ROC result suggests that combining IL-6, IL-8, CXCL9 and CXCL13 into a nomogram has closely correlation with HCC during chronic HBV infection. In addition, nucleotide analogues (NAs) antiviral treatments are capable of recoveringnormal liver functions and significantly reducing the viral loads, however, they seem to have a limited effect in changing CKs, especially specific antiviral factors. CONCLUSION: The differential CK and virological markers may serve as potential indicators of distinct immune statuses in chronic HBV infection. They also underscore the varying efficacy and limitations of NAs antiviral therapies. This next step would to break new ground in the optimization of current anti-HBV treatment programs although this requires further research.

Refinement and validation of a comprehensive clinical diagnostic model (GAMAD) based on gender, age, multitarget circulating tumour DNA methylation signature and commonly used serological biomarkers for early detection of hepatocellular carcinoma: a multicentre, prospective observational study protocol.

INTRODUCTION: Prompt detection of hepatocellular carcinoma (HCC) in patients with chronic liver diseases is critical for enhancing prognosis. Existing imaging techniques and serum markers fall short of clinical needs. This study aims to establish a non-invasive diagnostic model for early HCC detection in the Chinese population. METHODS AND ANALYSIS: This prospective, multicentre, observational study will enrol 2000 participants, including HCC patients, those with chronic liver diseases (hepatitis, cirrhosis and benign liver space-occupying lesions), and healthy individuals. The study will collect demographic data and blood samples, which will be used to test α-fetoprotein (AFP), des-γ-carboxy-prothrombin (DCP) and circulating tumour DNA (ctDNA) methylation. The GAMAD (Gender+Age+Methylation+AFP+DCP) model involving gender, age, ctDNA methylation signature, AFP and DCP will be developed and blindly validated in training and validation sets (1400 and 600 cases, respectively). Primary endpoints include sensitivity, specificity and accuracy (receiver operating characteristic curves; area under the curve value) of GAMAD for HCC and/or high-risk HCC groups. Secondary endpoints involve comparing GAMAD with the established GALAD (Gender+Age+AFP-L3+AFP+DCP) model and each blood index (AFP, DCP and methylation signature) to evaluate: (1) GAMAD's clinical utility for HCC patients in all stages according to different staging systems; (2) GAMAD's discrimination ability for patients in various subgroups, including liver cirrhosis (LC) related HCC and LC, hepatitis B virus (HBV) related HCC and HBV, hepatitis C virus (HCV) related HCC and HCV, and non-alcoholic fatty liver disease (NAFLD) related HCC and NAFLD. ETHICS AND DISSEMINATION: This trial has been approved by the Medical Ethics Committees of the First Hospital of Jilin University (#22K073-001), the Eastern Hepatobiliary Surgery Hospital, Naval Medical University (#EHBHKY2023-H0003-P001) and Tianjin Third Central Hospital (#IRB2023-007-01). All participants in the trial will provide written informed consent. Results of this study will be disseminated in peer-reviewed scientific journals and at conferences nationally and internationally. TRIAL REGISTRATION NUMBER: NCT05626985.

Male Breast Cancer: Three Case Reports and a Literature Review.

INTRODUCTION: Male breast cancer (MBC) accounts for 0.5%-1% of all breast cancers diagnosed worldwide. However, its biological characteristics can be distinguished from that of female breast cancer (FBC). CASE REPRESENTATION: The diagnostic and treatment approaches for MBC are mainly similar to that of FBC due to the lack of male breast cancer-related studies, clinical trials, and literature. An increasing number of retrospective and prospective studies have been conducted to clarify the individualized care for MBC. Herein, we report three cases of advanced MBC to describe the diagnostic approaches, treatment process, and survival prognosis. CONCLUSION: MBC patients had older age, later stage at first diagnosis, higher expression of hormone receptors, and poor prognosis. A literature review was conducted to determine the incidence, risk factors, disease features, diagnosis, treatment, survival, and management of MBC.

The Effects of Cinobufagin on Hepatocellular Carcinoma Cells Enhanced by MRT68921, an Autophagy Inhibitor.

Cinobufagin, a cardiotonic steroid derived from toad venom extracts, exhibits significant anticancer properties by inhibiting Na[Formula: see text]/K[Formula: see text]-ATPase in cancer cells. It is frequently used in clinical settings to treat advanced-stage cancer patients, improving their quality of life and survival time. However, its long-term use can result in multidrug resistance to other chemotherapy drugs, and the exact mechanism underlying this effect remains unknown. Therefore, this study explores the molecular mechanism underlying the anticancer effects of cinobufagin in hepatocellular carcinomas (HCCs), specifically in HepG2 and Huh-7 cells. As determined using transcriptome analysis, cinobufagin-triggered protective autophagy suppressed cell apoptosis in liver cancer HepG2 and Huh-7 cells by inhibiting the phosphoinositide-3-Kinase (PI3K)-AKT serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR) pathway. Cinobufagin-inhibited cell proliferation, induced apoptosis, and generated cell autophagy by upregulating the expression of MAP1 light chain 3 protein II, Beclin1, and autophagy-related protein 12-5. In addition, the autophagy inhibitor MRT68921 improved the antiproliferative and proapoptotic effects of cinobufagin in the studied cell lines. Overall, this study suggests that combining cinobufagin with an autophagy inhibitor can effectively treat HCC, providing a potential strategy for cancer therapy.

Combat Against Gynecological Cancers with Blood Vessels as Entry Point: Anti-Angiogenic Drugs, Clinical Trials and Pre-Clinical Nano-Delivery Platforms.

Angiogenesis is an essential mechanism for the progression of gynecological cancers. Although approved anti-angiogenic drugs have demonstrated clinical efficacy in treating gynecological cancers, the full potential of therapeutic strategies based on tumor blood vessels has not yet been realized. This review summarizes the latest angiogenesis mechanisms involved in the progression of gynecological cancers and discusses the current clinical practice of approved anti-angiogenic drugs and related clinical trials. Given the close relationship between gynecological cancers and blood vessels, we highlight more delicate strategies for regulating tumor vessels, including wise drug combinations and smart nano-delivery platforms to achieve highly efficient drug delivery and overall vessel microenvironment regulation. We also address current challenges and future opportunities in this field. We aim to generate interest in therapeutic strategies that target blood vessels as a key entry point and offer new potential and inspiration for combating gynecological cancers.

Ce Site in Amorphous Iron Oxyhydroxide Nanosheet toward Enhanced Electrochemical Water Oxidation.

Iron oxyhydroxide has been considered an auspicious electrocatalyst for the oxygen evolution reaction (OER) in alkaline water electrolysis due to its suitable electronic structure and abundant reserves. However, Fe-based materials seriously suffer from the tradeoff between activity and stability at a high current density above 100 mA cm-2 . In this work, the Ce atom is introduced into the amorphous iron oxyhydroxide (i.e., CeFeOx Hy ) nanosheet to simultaneously improve the intrinsic electrocatalytic activity and stability for OER through regulating the redox property of iron oxyhydroxide. In particular, the Ce substitution leads to the distorted octahedral crystal structure of CeFeOx Hy , along with a regulated coordination site. The CeFeOx Hy electrode exhibits a low overpotential of 250 mV at 100 mA cm-2 with a small Tafel slope of 35.1 mVdec-1 . Moreover, the CeFeOx Hy electrode can continuously work for 300 h at 100 mA cm-2 . When applying the CeFeOx Hy nanosheet electrode as the anode and coupling it with the platinum mesh cathode, the cell voltage for overall water splitting can be lowered to 1.47 V at 10 mA cm-2 . This work offers a design strategy for highly active, low-cost, and durable material through interfacing high valent metals with earth-abundant oxides/hydroxides.

Advancement in transporter-oriented nanoplatforms for cancer therapy.

Except for cell-surface receptors, a range of transporters have been exploited as targets for the delivery of novel anti-tumour nanomaterials. Transporters, which are essential for delivering nutrients for the biosynthesis of mammalian cells, are significantly expressed in a range of tumour types; their expression is mostly tissue- and site-specific. The unique functional and expression characteristics of transporters make them ideal targets for mediating the selective delivery of nanomaterials to cancer cells, thus promoting cell accumulation, and enhancing the penetration of nanomaterials into biological barriers before they can specifically target cancer cells. In this review, we discuss the unique function of cancer-related transporters in the initiation and development of tumours, as well as the use of transporter-targeted nanocarriers in tumour-targeting therapy. First, the expression of various transporters in tumorigenesis and development is reviewed; this is followed by a discussion of the latest advances in targeted drug delivery strategies based on transporter nanocarriers. Finally, we review the molecular mechanisms and targeting efficiency of transporter-mediated nanocarriers. This review provides a state-of-the-art synthesis of this discipline and will facilitate the generation of new concepts for the design of highly efficacious and tumour-targeting nanocarriers.

Predictive Value of Ablative Margin Assessment After Microwave Ablation for Local Tumor Progression in Medium and Large Hepatocellular Carcinoma: Computed Tomography-Computed Tomography Image Fusion Method Versus Side-by-Side Method.

OBJECTIVE: This study aimed to explore the feasibility and predictive value for local tumor progression (LTP) of the computed tomography (CT)-CT image fusion method versus side-by-side method to assess ablative margin (AM) in hepatocellular carcinoma ≥3 cm in diameter. MATERIALS AND METHODS: We selected patients with hepatocellular carcinoma ≥3 cm in diameter who underwent microwave ablation and had complete tumor ablation. We used the CT-CT image fusion method and side-by-side method to assess AM separately and divided the lesions into 3 groups: group I, minimum ablative margin (min-AM) <0 mm (the ablation zone did not fully cover the tumor); group II, 0 mm ≤ min-AM <5 mm; and group III, min-AM ≥5 mm. RESULTS: A total of 71 patients involving 71 lesions were included. The κ coefficient for the agreement between the CT-CT image fusion method and the side-by-side method in assessing min-AM was 0.14 (P = 0.028). Cumulative LTP rate was significantly different between groups by min-AM from the CT-CT image fusion method (P < 0.05) but not by min-AM from the side-by-side method (P = 0.807). Seventeen of the 20 LTP lesions were located at min-AM on fused CT images, with consistency rate of 85%. CONCLUSIONS: Compared with the side-by-side method, the CT-CT image fusion method is more accurate in assessing the AM of eccentrically ablated lesions and shows better predictive value for LTP. The min-AM based on CT-CT image fusion assessment is an important influencing factor for LTP.

Photocatalytic co-production of hydrogen gas and N-benzylidenebenzylamine over high-quality 2D layered In4/3P2Se6 nanosheets.

The concurrent photocatalytic synthesis of hydrogen gas and high-valued chemicals over two-dimensional semiconductors is extremely attractive to alleviate global energy and environmental concerns through directly using sunlight. Herein, a novel layered In4/3P2Se6 nanosheet is synthesized by a space confined chemical vapor conversion method, and it acts as a dual-functional photocatalyst to deliver the co-production of hydrogen gas and N-benzylidenebenzylamine from water reduction and selective benzylamine oxidation. The simultaneous yield of hydrogen gas and N-benzylidenebenzylamine is 895 µmol g-1 and 681 µmol g-1, respectively, within 16-hour continuous reaction involving a small amount of water in acetonitrile solvent. Moreover, 97.4% N-benzylidenebenzylamine selectivity from benzylamine oxidation can be achieved with continuous 10 hour-reaction only in acetonitrile solvent under ambient conditions. Further in situ electron paramagnetic resonance measurements and reaction optimization tests reveal that the reaction mechanism strongly relies on the conditions over the In4/3P2Se6 nanosheet photocatalyst.

Describing immune factors associated with Hepatitis B surface antigen loss: A nested case-control study of a Chinese sample from Wuwei City.

Background: Hepatitis B surface antigen (HBsAg) loss is considered a functional cure for chronic hepatitis B (CHB), however, several factors influence HBsAg loss. Methods: 29 CHB patients who had achieved HBsAg loss, were selected and 58 CHB patients with persistent HBsAg were matched, according to gender and age (+/- 3 years). Logistic regression and restricted cubic spline (RCS) modelling were performed. Results: Multivariate-adjusted logistic regression, based on stepwise selection, showed that baseline HBsAg levels negatively correlated with HBsAg loss (odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.98-0.99). Interferon treatment positively related with HBsAg loss (OR = 7.99, 95%CI = 1.62-44.88). After adjusting for age, HBsAg level, ALT level, HBeAg status and interferon treatment, MMP-1 (OR = 0.66, 95%CI = 0.44-0.97), CXCL9 (OR = 0.96, 95%CI = 0.93-0.99) and TNF-R1 (OR = 0.97, 95%CI = 0.94-0.99) baseline levels all negatively correlated with HBsAg loss. Our multivariate-adjusted RCS model showed that baseline CXCL10 was associated with HBsAg loss although the relationship was "U-shaped". Conclusions: Cytokines such as MMP-1, CXCL9, CXCL10 and TNF-R1 are important factors which influence HBsAg loss. It may be possible to develop a nomogram which intercalates these factors; however, further research should consider immune processes involved in HBsAg loss.

Associations of left renal vein entrapment with IgA nephropathy and Henoch-Schönlein purpura nephritis.

OBJECTIVES: The aims of the study were to identify whether left renal vein (LRV) entrapment was more prevalent in IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) compared with other types of renal diseases, and the association of LRV entrapment with glomerular incidental IgA and galactose-deficient-IgA1 (Gd-IgA1) deposition. METHODS: A total of 797 patients with biopsy-proven kidney diseases have been screened for LRV entrapment by color Doppler ultrasound, and the prevalence of LRV entrapment in different types of renal diseases were then analyzed. Propensity score matching analysis was used to adjust for age, gender, and body mass index. Immunostaining of Gd-IgA1 with KM55 was performed in paraffin-embedded sections of renal biopsy specimens. RESULTS: LRV entrapment was diagnosed in 47 patients (6%) with several kinds of renal diseases in our cohort. A total of 32 (68%) LRV entrapments were combined with expanded IgAN (idiopathic IgAN and HSPN). The prevalence of LRV entrapment in expanded IgAN was significantly higher than that in non-expanded IgAN (17 vs. 2%, p < 0.001), even after adjustment for age, gender, and body mass index by propensity score matching analysis (13 vs. 2%, p < 0.001). Removing expanded IgAN and LN, glomerular incidental IgA deposition was observed to be significantly more common in patients with LRV entrapment compared with patients without it (43 vs. 9%, p < 0.001). Furthermore, in glomerular diseases with incidental IgA deposits, significantly much larger proportion of patients with LRV entrapment were positive for glomerular Gd-IgA1 in contrast to patients without LRV entrapment (5/5 vs. 5/17, p = 0.01). CONCLUSIONS: LRV entrapment coexisted with several kinds of renal diseases, with a significantly higher prevalence in patients with idiopathic IgAN and HSPN. In patients of LN and IgAN-unrelated disease with LRV entrapment, glomerular IgA and Gd-IgA1 deposition was more common compared with patients without LRV entrapment.

Risk Stratification and Distribution of Hepatocellular Carcinomas in CEUS and CT/MRI LI-RADS: A Meta-Analysis.

Background: CEUS LI-RADS and CT/MRI LI-RADS have been used in clinical practice for several years. However, there is a lack of evidence-based study to compare the proportion of hepatocellular carcinomas (HCCs) in each category and the distribution of HCCs of these two categorization systems. Purpose: The purpose of this study was to compare the proportion of HCCs between corresponding CEUS LI-RADS and CT/MRI LI-RADS categories and the distribution of HCCs and non-HCC malignancies in each category. Methods: We searched PubMed, Embase, and Cochrane Central databases from January 2014 to December 2021. The proportion of HCCs and non-HCC malignancies and the corresponding sensitivity, specificity, accuracy, diagnostic odds ratio (DOR), and area under the curve (AUC) of the LR-5 and LR-M categories were determined using a random-effect model. Results: A total of 43 studies were included. The proportion of HCCs in CEUS LR-5 was 96%, and that in CECT/MRI LR-5 was 95% (p > 0.05). The proportion of non-HCC malignancy in CEUS LR-M was lower than that of CT/MRI LR-M (35% vs. 58%, p = 0.01). The sensitivity, specificity, and accuracy of CEUS LR-5 for HCCs were 73%, 92%, and 78%, respectively, and of CT/MRI LR-5 for HCCs, 69%, 92%, and 76%, respectively. Conclusion: With the upshift of the LI-RADS category, the proportion of HCCs increased. CEUS LR-3 has a lower risk of HCCs than CT/MRI LR-3. CEUS LR-5 and CT/MRI LR-5 have a similar diagnostic performance for HCCs. CEUS LR-M has a higher proportion of HCCs and a lower proportion of non-HCC malignancies compared with CT/MRI LR-M.

Combination of CT/MRI LI-RADS with CEUS can improve the diagnostic performance for HCCs.

BACKGROUND & AIMS: To compare the classifications for focal liver lesions smaller than 3 cm by the CEUS and CT/MRI LI-RADS and explore the discrepancy between the two classifications strategies. METHODS: Focal liver lesions with a size smaller than 3 cm undergoing CEUS and CT/MRI (MR required on a 3.0 T magnet) within 1 month were enrolled. Each nodule was categorized according to the CEUS LI-RADS v2017 (usLI-RADS) and CT/MRI LI-RADS v2018. Intermodality agreement between the usLI-RADS and LI-RADS for CT/MRI was assessed. The reasons for inconsistent classifications by the CEUS and CT/MRI LI-RADS were clarified. RESULTS: A total of 213 lesions were included. The positive predictive value (PPV) for HCCs of LR-3, 4 and 5 were 57.1% (95% CI: 32.6-78.6), 75.0% (95% CI: 62.3-84.5) and 94.2% (95% CI: 88.9-97.0) for CT/MRI and 37.5% (95% CI: 18.5-61.4), 56.0% (95% CI: 37.1-73.3) and 97.9% (95% CI: 94.1-99.3) for CEUS, respectively. CECT/MRI and CEUS LI-RADS had a poor agreement in classification with a kappa value of 0.254 (P < 0.001). 84 lesions (39.4%) were classified inconsistently in CT/MRI and CEUS LI-RADS. 40 lesions classified as LR-3 or LR-4 by CT/MRI were upgraded by CEUS. 21 lesions classified as LR-4 or LR-5 by CT/MRI were downgraded by CEUS. We reclassified the lesion in CT/MRI LR-3 and LR-4 by CEUS. The PPVs for HCCs in reclassified LR-3, LR-4 and LR-5 were 27.3% (95% CI: 9.7-56.6), 41.7% (95% CI: 26.2-69.0) and 94.2% (95% CI: 89.3-97.0), respectively, which decreased the incidences of HCCs in CT/MRI LR-3 and LR-4. CONCLUSION: Lesions in CT/MRI LR-3 and 4 have a higher probability of being HCCs than those in usLR-3 and 4, respectively. Reclassification of lesions in CT/MRI LR-3 and 4 using CEUS can help the corresponding HCCs get a definite diagnosis.