Clinical application of dual-layer spectral CT multi-parameter feature to predict microvascular invasion in hepatocellular carcinoma.

OBJECTIVE: This study aimed to investigate the feasibility of using dual-layer spectral CT multi-parameter feature to predict microvascular invasion of hepatocellular carcinoma. METHODS: This retrospective study enrolled 50 HCC patients who underwent multiphase contrast-enhanced spectral CT studies preoperatively. Combined clinical data, radiological features with spectral CT quantitative parameter were constructed to predict MVI. ROC was applied to identify potential predictors of MVI. The CT values obtained by simulating the conventional CT scans with 70 keV images were compared with those obtained with 40 keV images. RESULTS: 50 hepatocellular carcinomas were detected with 30 lesions (Group A) with microvascular invasion and 20 (Group B) without. There were significant differences in AFP,tumer size, IC, NIC,slope and effective atomic number in AP and ICrr in VP between Group A ((1000(10.875,1000),4.360±0.3105, 1.7750 (1.5350,1.8825) mg/ml, 0.1785 (0.1621,0.2124), 2.0362±0.2108,8.0960±0.1043,0.2830±0.0777) and Group B (4.750(3.325,20.425),3.190±0.2979,1.4700 (1.4500,1.5775) mg/ml, 0.1441 (0.1373,0.1490),1.8601±0.1595, 7.8105±0.7830 and 0.2228±0.0612) (all p < 0.05). Using 0.1586 as the threshold for NIC, one could obtain an area-under-curve (AUC) of 0.875 in ROC to differentiate between tumours with and without microvascular invasion. AUC was 0.625 with CT value at 70 keV and improved to 0.843 at 40 keV. CONCLUSION: Dual-layer spectral CT provides additional quantitative parameters than conventional CT to enhance the differentiation between hepatocellular carcinoma with and without microvascular invasion. Especially, the normalized iodine concentration (NIC) in arterial phase has the greatest potential application value in determining whether microvascular invasion exists, and can offer an important reference for clinical treatment plan and prognosis assessment.

Landscape of gut mucosal immune cells showed gap of follicular or memory B cells into plasma cells in immunological non-responders.

BACKGROUND: The gut is an important site for human immunodeficiency virus (HIV) infection and immune responses. The role of gut mucosal immune cells in immune restoration in patients infected with HIV undergoing antiretroviral therapy remains unclear. METHODS: Ileocytes, including 54 475 immune cells, were obtained from colonoscopic biopsies of five HIV-negative controls, nine immunological responders (IRs), and three immunological non-responders (INRs) and were analyzed using single-cell RNA sequencing. Immunohistochemical assays were performed for validation. The 16S rRNA gene was amplified using PCR in faecal samples to analyze faecal microbiota. Flow cytometry was used to analyze CD4+ T-cell counts and the activation of T cells. RESULTS: This study presents a global transcriptomic profile of the gut mucosal immune cells in patients infected with HIV. Compared with the IRs, the INRs exhibited a lower proportion of gut plasma cells, especially the IGKC+IgA+ plasma cell subpopulation. IGKC+IgA+ plasma cells were negatively associated with enriched f. Prevotellaceae the INRs and negatively correlated with the overactivation of T cells, but they were positively correlated with CD4+ T-cell counts. The INRs exhibited a higher proportion of B cells than the IRs. Follicular and memory B cells were significantly higher in the INRs. Reduced potential was observed in the differentiation of follicular or memory B cells into gut plasma cells in INRs. In addition, the receptor-ligand pairs CD74_MIF and CD74_COPA of memory B/ follicular helper T cells were significantly reduced in the INRs, which may hinder the differentiation of memory and follicular B cells into plasma cells. CONCLUSIONS: Our study shows that plasma cells are dysregulated in INRs and provides an extensive resource for deciphering the immune pathogenesis of HIV in INRs. KEY POINTS: An investigation was carried out at the single-cell-level to analyze gut mucosal immune cells alterations in PLWH after ART. B cells were significantly increased and plasma cells were significantly decreased in the INRs compared to the IRs and NCs. There are gaps in the transition from gut follicular or memory B cellsinto plasma cells in INRs.

Safety, immunogenicity and protective effect of sequential vaccination with inactivated and recombinant protein COVID-19 vaccine in the elderly: a prospective longitudinal study.

The safety and efficacy of COVID-19 vaccines in the elderly, a high-risk group for severe COVID-19 infection, have not been fully understood. To clarify these issues, this prospective study followed up 157 elderly and 73 young participants for 16 months and compared the safety, immunogenicity, and efficacy of two doses of the inactivated vaccine BBIBP-CorV followed by a booster dose of the recombinant protein vaccine ZF2001. The results showed that this vaccination protocol was safe and tolerable in the elderly. After administering two doses of the BBIBP-CorV, the positivity rates and titers of neutralizing and anti-RBD antibodies in the elderly were significantly lower than those in the young individuals. After the ZF2001 booster dose, the antibody-positive rates in the elderly were comparable to those in the young; however, the antibody titers remained lower. Gender, age, and underlying diseases were independently associated with vaccine immunogenicity in elderly individuals. The pseudovirus neutralization assay showed that, compared with those after receiving two doses of BBIBP-CorV priming, some participants obtained immunological protection against BA.5 and BF.7 after receiving the ZF2001 booster. Breakthrough infection symptoms last longer in the infected elderly and pre-infection antibody titers were negatively associated with the severity of post-infection symptoms. The antibody levels in the elderly increased significantly after breakthrough infection but were still lower than those in the young. Our data suggest that multiple booster vaccinations at short intervals to maintain high antibody levels may be an effective strategy for protecting the elderly against COVID-19.

Investigation of synthetic MRI with quantitative parameters for discriminating axillary lymph nodes status in invasive breast cancer.

OBJECTIVE: To investigate the potential value of quantitative parameters derived from synthetic magnetic resonance imaging (syMRI) for discriminating axillary lymph nodes metastasis (ALNM) in breast cancer patients. MATERIALS AND METHODS: A total of 56 females with histopathologically proven invasive breast cancer who underwent both conventional breast MRI and additional syMRI examinations were enrolled in this study, including 30 patients with ALNM and 26 with non-ALNM. SyMRI has enabled quantification of T1 relaxation time (T1), T2 relaxation time (T2) and proton density (PD). The syMRI quantitative parameters of breast primary tumors before (T1tumor, T2tumor, PDtumor) and after (T1+tumor, T2+tumor, PD+tumor) contrast agent injection were obtained. Similarly, measurements were taken for axillary lymph nodes before (T1LN, T2LN, PDLN) and after (T1+LN, T2+LN, PD+LN) the injection, then theΔT1 (T1-T1+), ΔT2 (T2-T2+), ΔPD (PD-PD+), T1/T2 and T1+/T2+ were calculated. All parameters were compared between ANLM and non-ALNM group. Intraclass correlation coefficient for assessing interobserver agreement. The independent Student's t test or Mann-Whitney U test to determine the relationship between the mean quantitative values and the ALNM. Multivariate logistic regression analyses followed by receiver operating characteristics (ROC) analysis for discriminating ALN status. A P value < 0.05 was considered statistically significant. RESULTS: The short-diameter of lymph nodes (DLN) in ALNM group was significantly longer than that in the non-ALNM group (10.22 ± 3.58 mm vs. 5.28 ± 1.39 mm, P < 0.001). The optimal cutoff value was determined to be 5.78 mm, with an AUC of 0.894 (95 % CI: 0.838-0.939), a sensitivity of 86.7 %, and a specificity of 90.2 %. In syMRI quantitative parameters of breast tumors, T2tumor, ΔT2tumor and ΔPDtumor values showed statistically significant differences between the two groups (P < 0.05). T2tumor value had the best performance in discriminating ALN status (AUC = 0.712), and the optimal cutoff was 90.12 ms, the sensitivity and specificity were 65.0 % and 83.6 % respectively. In terms of syMRI quantitative parameters of lymph nodes, T1LN, T2LN, T1LN/T2LN, T2+LN and ΔT1LN values were significantly different between the two groups (P < 0.05), and their AUCs were 0.785, 0.840, 0.886, 0.702 and 0.754, respectively. Multivariate analyses indicated that the T1LN value was the only independent predictor of ALNM (OR=1.426, 95 % CI: 1.130-1.798, P = 0.039). The diagnostic sensitivity and specificity of T1LN was 86.7 % and 69.4 % respectively at the best cutoff point of 1371.00 ms. The combination of T1LN, T2LN, T1LN/T2LN, ΔT1LN and DLN had better performance for differentiating ALNM and non-ALNM, with AUCs of 0.905, 0.957, 0.964 and 0.897, respectively. CONCLUSION: The quantitative parameters derived from syMRI have certain value for discriminating ALN status in invasive breast cancer, with T2tumor showing the highest diagnostic efficiency among breast lesions parameters. Moreover, T1LN acted as an independent predictor of ALNM.

Diagnostic performance of MRI for assessing axillary lymph node status after neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis.

OBJECTIVE: This systematic review examined the diagnostic performance of magnetic resonance imaging (MRI) for assessing axillary lymph node status (ALNS) after neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science to identify relevant studies and used the QUADAS-2 tool to assess methodological quality of eligible studies. We used STATA version 12.0 to perform data pooling, heterogeneity testing, subgroup analysis, and sensitivity analysis. RESULTS: For the 21 enrolled studies, including 2875 patients, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were respectively 0.63 (95% CI: 0.53-0.72), 0.75 (95% CI: 0.68-0.81), 2.52 (95% CI: 1.98-3.19), 0.50 (95% CI: 0.39-0.63), and 5.08 (95% CI: 3.38-7.63). The AUC was 0.76 (95% CI: 0.72-0.79). I2 values of sensitivity (I2 = 94.41%) and specificity (I2 = 88.97%) were both > 50%. For the initial positive ALN patients, the pooled sensitivity and specificity were 0.64 (95% CI: 0.53-0.75) and 0.74 (95% CI: 0.64-0.82), respectively. Sensitivity analyses by focusing on studies with MRI performed post-NAC, studies using DCE-MRI, or studies with low risk of bias showed similar results to the primary analyses. CONCLUSION: MRI may have suboptimal diagnostic value in assessing ALNS after NAC for breast cancer patients. Due to the inconsistency of NAC regimens, the variability of axillary surgery, and the lack of time interval between MRI and surgery, further studies are needed to confirm our findings. CLINICAL RELEVANCE STATEMENT: Our study provided the diagnostic value of MRI in assessing axillary lymph node status after neoadjuvant chemotherapy for breast cancer patients. KEY POINTS: • MRI may have suboptimal diagnostic value in assessing axillary lymph node status after NAC for general breast cancer patients. • The initial axillary lymph node status has little impact on the diagnostic efficacy of MRI. • The substantial heterogeneity among studies highlights the need for further studies to provide more high-quality evidence in this field.

Characteristics of blood immune cell profile and their correlation with disease progression in patients infected with HIV-1.

BACKGROUND: Antiretroviral therapy (ART) can reduce viral load in individuals infected with human immunodeficiency virus (HIV); however, some HIV-infected individuals still cannot achieve optimal immune recovery even after ART. Hence, we described the profile of peripheral immune cells and explored the association with disease progression in patients infected with HIV-1. METHODS: Mass cytometry analysis was used to characterize the circulating immune cells of 20 treatment-naïve (TNs), 20 immunological non-responders (INRs), 20 immunological responders (IRs), and 10 healthy controls (HCs). Correlation analysis was conducted between cell subpopulation percentages and indicators including HIV-1 cell-associated (CA)-RNA, DNA, CD4+ T cell count, and CD4/CD8 ratio. RESULTS: Global activation, immunosenescence, and exhaustion phenotypes were observed in myeloid cells and T cells from individuals with HIV-1 infection. We also found that specific subsets or clusters of myeloid, CD4+ T, and CD8+ T cells were significantly lost or increased in TN individuals, which could be partially restored after receiving ART. The percentages of several subpopulations correlated with HIV-1 CA-RNA, DNA, CD4+ T cell count, and CD4/CD8 ratio, suggesting that changes in immune cell composition were associated with therapeutic efficacy. CONCLUSION: These data provide a complete profile of immune cell subpopulations or clusters that are associated with disease progression during chronic HIV-1 infection, which will improve understanding regarding the mechanism of incomplete immune recovery in INRs.

Effect of SARS-CoV-2 Breakthrough Infection on HIV Reservoirs and T-Cell Immune Recovery in 3-Dose Vaccinated People Living with HIV.

People living with human immunodeficiency virus (PLWH) are a vulnerable population with a higher risk of severe coronavirus disease 2019 (COVID-19); therefore, vaccination is recommended as a priority. Data on viral reservoirs and immunologic outcomes for PLWH breakthrough infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently limited. In this study, we investigated the effects of SARS-CoV-2 breakthrough infection on hematological parameters, human immunodeficiency virus (HIV) reservoir size, and T-cell recovery in PLWH receiving antiretroviral therapy (ART) after SARS-CoV-2 booster vaccination. The results indicated that during breakthrough infection, booster vaccination with homologous and heterologous vaccines was safe in PLWH after receiving two doses of inactivated vaccination. The absolute CD4 counts decreased in the heterologous group, whereas the CD8 counts decreased in the homologous booster group after breakthrough infection in PLWH. Breakthrough infection increased HIV reservoirs and was associated with increased T-cell activation in PLWH who received virally suppressed ART and a 3-dose vaccination. According to our data, the breakthrough infection of SARS-CoV-2 may put PLWH at a greater risk for increased HIV reservoirs, even if these individuals were virally suppressed with ART after 3-dose SARS-CoV-2 vaccination.

Severe intestinal barrier damage in HIV-infected immunological non-responders.

The intestinal epithelial barrier plays an important role during human immunodeficiency virus (HIV) disease progression. However, the extent to which the intestinal epithelial barrier is damaged in immunological non-responders (INRs) and immunological responders (IRs) is largely unknown. In this study, we investigated and compared the levels of intestinal gland damage and related molecules, including the tight junction protein claudin-1, apoptosis marker caspase-3, HIV DNA, CD4+ T cell count, and inflammation marker tumor necrosis factor-α (TNF-α) among the IRs (n = 10), INRs (n = 8), and healthy controls (HCs, n = 7). Intestinal damage was not completely restored in both INRs and IRs and was more serious in INRs than that in IRs. Moreover, intestinal damage was positively correlated with HIV DNA levels and negatively correlated with CD4+ T cell counts. These results provide insight into understanding the characteristics of intestinal epithelial barrier damage between IRs and INRs.

Abnormal blood microbiota profiles are associated with inflammation and immune restoration in HIV/AIDS individuals.

IMPORTANCE: The characteristics of blood microbiota in HIV-infected individuals and their relevance to disease progression are still unknown, despite alterations in gut microbiota diversity and composition in HIV-infected individuals. Here, we present evidence of increased blood microbiota diversity in HIV-infected individuals, which may result from gut microbiota translocation. Also, we identify a group of microbes, Porphyromonas gingivalis, Prevotella sp. CAG:5226, Eubacterium sp. CAG:251, Phascolarctobacterium succinatutens, Anaerobutyricum hallii, Prevotella sp. AM34-19LB, and Phocaeicola plebeius, which are linked to poor immunological recovery. This work provides a scientific foundation toward therapeutic strategies targeting blood microbiota for immune recovery of HIV infection.

The Imbalance Between Intestinal Th17 and Treg Cells Is Associated with an Incomplete Immune Reconstitution During Long-Term Antiretroviral Therapy in Patients with HIV.

Studies assessing the gut mucosal immune balance in HIV-infected patients using intestinal samples are scarce. In this study, we used intestinal mucosal specimens from the ileocecal region of seven immunological nonresponders (INRs), nine immunological responders (IRs), and six HIV-negative controls. We investigated T helper 17 (Th17) and T regulatory (Treg) cell counts and their ratio, zonula occludens-1 (ZO-1), intestinal fatty acid-binding protein (I-FABP), tumor necrosis factor-α, CD4+ T cell counts, HIV DNA, and cell-associated HIV RNA. The results showed that INRs had lower Th17 and higher Treg cell counts than IR, resulting in a significant difference in the Th17/Treg ratio between IRs and INRs. In addition, INRs had lower ZO-1 and higher I-FABP levels than IRs. The Th17/Treg ratio was positively associated with ZO-1 and negatively associated with I-FABP levels. There was a positive correlation between Th17/Treg ratio and CD4+ T cell counts and a negative correlation between the Th17/Treg ratio and HIV DNA in the intestine. Our study suggests that the imbalance of Th17/Treg in the intestine is a characteristic of incomplete immune reconstitution to antiretroviral therapy and is associated with intestinal damage.

Knockout of OsNRAMP5 enhances rice tolerance to cadmium toxicity in response to varying external cadmium concentrations via distinct mechanisms.

OsNRAMP5 is a transporter responsible for cadmium (Cd) and manganese (Mn) uptake and root-to-shoot translocation of Mn in rice plants. Knockout of OsNRAMP5 is regarded as an effective approach to minimize Cd uptake and accumulation in rice. It is vital to evaluate the effects of knocking out OsNRAMP5 on Cd and Mn accumulation, as well as Cd tolerance of rice plants in response to varying environmental Cd concentrations, and to uncover the underlying mechanism, which until now, has remained largely unexplored. This study showed that knockout of OsNRAMP5 decreased Cd uptake, but simultaneously facilitated Cd translocation from roots to shoots. The effect of OsNRAMP5 knockout on reducing root Cd uptake weakened, however its effect on improving root-to-shoot Cd translocation was constant with increasing environmental Cd concentrations. As a result, its mutation dramatically reduced Cd accumulation in shoots under low and moderate Cd stress, but inversely increased that under high Cd conditions. Interestingly, Cd tolerance of its knockout mutants was persistently enhanced, irrespective of lower or higher Cd concentrations in shoots, compared with that of wild-type plants. Knockout of OsNRAMP5 mitigated Cd toxicity by dramatically diminishing Cd uptake at low or moderate external Cd concentrations. Remarkably, its knockout effectively complemented deficient mineral nutrients in shoots, thereby indirectly enhancing rice tolerance to severe Cd stress. Additionally, its mutation conferred preferential delivery of Mn to young leaves and grains. These results have important implications for the application of the OsNRAMP5 mutation in mitigating Cd toxicity and lowering the risk of excessive Cd accumulation in rice grains.

Synchronous double primary hepatocellular carcinoma and intrahepatic cholangiocarcinoma: A case report and review of the literature.

RATIONALE: Presence of synchronous double hepatocelluar carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) (sdpHCC-ICC) located separately within a single liver is extremely rare. The purpose of this study is to investigate the clinical, imaging, pathological characteristics, and prognosis of patients with sdpHCC-ICC, in order to enhance our understanding of the disease and improve diagnostic and therapeutic effect. PATIENT CONCERNS: A 49-year-old, female with the diagnosis of hepatitis B virus with obvious liver cirrhosis, was admitted to our hospital. On admission, the levels of α-fetoprotein and carbohydrate antigen 19-9 were found to be elevated. Abdominal ultrasonography and enhanced computed tomography revealed 2 solid masses located in segments (S) 4 and 6 of the liver, with malignant behaviors. DIAGNOSES: In the light of above investigations, preoperative diagnosis of multiple primary hepatocellular carcinomas was made. INTERVENTION: Hepatic resection of both segments was done. The resected specimens revealed the presence of well-defined tumors in segments 4 and 6 measuring 5.0 cm and 2.5 cm respectively. OUTCOMES: Histopathological examination confirmed the tumor of the 4th segment to be moderately and poorly differentiated ICC, and the tumor of the 6th segment to be poorly differentiated HCC. Immunohistochemically, the ICC in S4 was positive for CK19 and negative for Heppar-1, whereas the HCC in S6 was positive for Heppar-1 and negative for CK19. Unfortunately, metastasis to multiple organs and lymph nodes were observed 3 months later. The patient died of liver failure 16 months after surgery. LESSONS: The clinical characteristics of sdpHCC-ICC are usually atypical and nonspecific making its preoperative diagnosis quite difficult. Hepatitis B virus and hepatitis C virus infection were both the independent risk factor for the development of sdpHCC-ICC. In patients with chronic liver disease, careful observation with imaging is of utmost necessity. Tumor markers may also play a valuable role in the diagnosis. The definite diagnosis depends on pathological examination. Hepatic resection is considered the most effective mode of treatment. The prognosis of synchronous occurrence of double hepatic cancers is worse than either HCC or ICC, and the origin of the disease needs further study.

The diagnostic performance of diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging in evaluating the pathological response of breast cancer to neoadjuvant chemotherapy: A meta-analysis.

PURPOSE: To evaluate and compare the diagnostic performance of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the pathological response of breast cancer to neoadjuvant chemotherapy (NAC). METHODS: We searched PubMed, EMBASE, Cochrane Library, and Web of Science systematically to identify relevant studies from inception to December 2020. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess the methodological quality of the included studies. We extracted sufficient data to construct 2 × 2 tables and then used STATA 12.0 to perform data pooling, heterogeneity testing, meta-regression analysis and subgroup analysis. RESULTS: A total of 41 articles were enrolled in this study, including 27 studies (2107 patients) on DCE-MRI and 23 studies (1321 patients) on DWI. The pooled sensitivity and specificity of DCE-MRI were 0.75 and 0.79, and the pooled sensitivity and specificity of DWI were 0.77 and 0.75. There was no significant difference in sensitivity (P = 0.598) and specificity (P = 0.218) ​​between DCE-MRI and DWI. And meta-regression analysis showed that both magnetic field strength and the time of examination had significant effects on heterogeneity. CONCLUSIONS: DWI might be a potential substitute for DCE-MRI in predicting the pathological response of breast cancer to NAC as there was no significant difference in the diagnostic performance between the two. However, considering that not all included studies directly compared the diagnostic performance of DWI and DCE-MRI in the same patients and the heterogeneity of the included studies, caution should be exercised in applying our results.

LjaFGD: Lonicera japonica functional genomics database.

Lonicera japonica Thunb., a traditional Chinese herb, has been used for treating human diseases for thousands of years. Recently, the genome of L. japonica has been decoded, providing valuable information for research into gene function. However, no comprehensive database for gene functional analysis and mining is available for L. japonica. We therefore constructed LjaFGD (www.gzybioinformatics.cn/LjaFGD and bioinformatics.cau.edu.cn/LjaFGD), a database for analyzing and comparing gene function in L. japonica. We constructed a gene co-expression network based on 77 RNA-seq samples, and then annotated genes of L. japonica by alignment against protein sequences from public databases. We also introduced several tools for gene functional analysis, including Blast, motif analysis, gene set enrichment analysis, heatmap analysis, and JBrowse. Our co-expression network revealed that MYB and WRKY transcription factor family genes were co-expressed with genes encoding key enzymes in the biosynthesis of chlorogenic acid and luteolin in L. japonica. We used flavonol synthase 1 (LjFLS1) as an example to show the reliability and applicability of our database. LjaFGD and its various associated tools will provide researchers with an accessible platform for retrieving functional information on L. japonica genes to further biological discovery.

Patient hematology during hospitalization for viral pneumonia caused by SARS-CoV-2 and non-SARS-CoV-2 agents: a retrospective study.

BACKGROUND: Hematological comparison of coronavirus disease (COVID-19) and other viral pneumonias can provide insights into COVID-19 treatment. METHODS: In this retrospective case-control single-center study, we compared the data of 126 patients with viral pneumonia during different outbreaks [severe acute respiratory syndrome (SARS) in 2003, influenza A (H1N1) in 2009, human adenovirus type 7 in 2018, and COVID-19 in 2020]. RESULTS: One of the COVID-19 characteristics was a continuous decline in the hemoglobin level. The neutrophil count was related to the aggravation of COVID-19 and SARS. Thrombocytopenia occurred in patients with SARS and severe COVID-19 even at the recovery stage. Lymphocytes were related to the entire course of adenovirus infection, recovery of COVID-19, and disease development of SARS. CONCLUSIONS: Dynamic changes in hematological counts could provide a reference for the pathogenesis and prognosis of pneumonia caused by respiratory viruses in clinics.

Diagnostic role of 18F-FDG PET/MRI in the TNM staging of breast cancer: a systematic review and meta-analysis.

BACKGROUND: To investigate the value of 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) in diagnosing local tumor invasion (T stage), evaluating regional lymph node involvement (N stage), and detecting distant metastasis (M stage) in breast cancer patients. METHODS: A comprehensive computer search and manual search were performed to select any potentially eligible studies that evaluated the diagnostic efficacy of 18F-FDG PET/MRI in the tumor-node-metastasis (TNM) staging of breast cancer. Data from the included studies were extracted to calculate the pooled sensitivity, specificity, and area under the curve (AUC) to evaluate the value of 18F-FDG PET/MRI in TNM staging. Quality and publication bias were also assessed in this meta-analysis. RESULTS: Based on seven studies, the pooled sensitivity, specificity and AUC for the diagnosis of T stage were 91% (95% CI: 84-96%), 91% (95% CI: 81-96%), and 0.96 (95% CI: 0.94-0.98), respectively. For N stage evaluation, four studies were included, with values of 94% (95% CI: 83-98%), 90% (95% CI: 81-95%), and 0.96 (95% CI: 0.94-0.97). For M stage detection, five studies were evaluated, with values of 98% (95% CI: 96-99%), 96% (95% CI: 83-99%), and 0.99 (95% CI: 0.98-1.00). CONCLUSIONS: 18F-FDG PET/MRI demonstrates higher diagnostic value in the TNM staging of breast cancer and can serve as an effective and promising imaging biomarker for future evaluation of TNM stage in breast cancer patients.

Filovirus VP24 Proteins Differentially Regulate RIG-I and MDA5-Dependent Type I and III Interferon Promoter Activation.

Filovirus family consists of highly pathogenic viruses that have caused fatal outbreaks especially in many African countries. Previously, research focus has been on Ebola, Sudan and Marburg viruses leaving other filoviruses less well studied. Filoviruses, in general, pose a significant global threat since they are highly virulent and potentially transmissible between humans causing sporadic infections and local or widespread epidemics. Filoviruses have the ability to downregulate innate immunity, and especially viral protein 24 (VP24), VP35 and VP40 have variably been shown to interfere with interferon (IFN) gene expression and signaling. Here we systematically analyzed the ability of VP24 proteins of nine filovirus family members to interfere with retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated antigen 5 (MDA5) induced IFN-ß and IFN-λ1 promoter activation. All VP24 proteins were localized both in the cell cytoplasm and nucleus in variable amounts. VP24 proteins of Zaire and Sudan ebolaviruses, Lloviu, Taï Forest, Reston, Marburg and Bundibugyo viruses (EBOV, SUDV, LLOV, TAFV, RESTV, MARV and BDBV, respectively) were found to inhibit both RIG-I and MDA5 stimulated IFN-ß and IFN-λ1 promoter activation. The inhibition takes place downstream of interferon regulatory factor 3 phosphorylation suggesting the inhibition to occur in the nucleus. VP24 proteins of Mengla (MLAV) or Bombali viruses (BOMV) did not inhibit IFN-ß or IFN-λ1 promoter activation. Six ebolavirus VP24s and Lloviu VP24 bound tightly, whereas MARV and MLAV VP24s bound weakly, to importin α5, the subtype that regulates the nuclear import of STAT complexes. MARV and MLAV VP24 binding to importin α5 was very weak. Our data provides new information on the innate immune inhibitory mechanisms of filovirus VP24 proteins, which may contribute to the pathogenesis of filovirus infections.

Metabolic defects in splenic B cell compartments from patients with liver cirrhosis.

Liver cirrhosis is associated with defective vaccine responses and increased infections. Dysregulated B cell compartments in cirrhotic patients have been noticed but not well characterized, especially in the spleen. Here, we comprehensively investigated B cell perturbations from the spleens and peripheral blood of cirrhotic patients. We found that liver cirrhosis significantly depleted both switched and nonswitched splenic memory B cells, which was further confirmed histologically. Bulk RNA-seq revealed significant metabolic defects as the potential mechanism for the impaired splenic B cell functions. Functionally, the splenic memory B cells from cirrhotic patients showed strong metabolic defects and reduced proliferation compared with those from healthy controls. Thus, liver cirrhosis extensively disturbs the splenic and peripheral B cell compartments, which may contribute to defective humoral immunity during liver cirrhosis.

Single-cell RNA sequencing reveals the heterogeneity of liver-resident immune cells in human.

The liver plays a critical role in both immune defense and tolerance in the body. The liver-resident immune cells (LrICs) determine the immune properties, but the unique composition and heterogeneity of these cells are incompletely understood. Here, we dissect the diversity of LrICs by a comprehensive transcriptomic profiling using the unbiased single-cell RNA-sequencing (scRNA-seq). A total of 70, 706 of CD45+ immune cells from the paired liver perfusion, spleen and peripheral blood as references were profiled. We identified more than 30 discrete cell populations comprising 13 of T and NK cell, 7 of B cell, 4 of plasma cell, and 8 of myeloid cell subsets in human liver and donor-paired spleen and blood, and characterized their tissue distribution, gene expression and functional modules. Especially, four of CXCR6+ T and NK cell subsets were found to be present preferentially in the liver, where they manifested heterogeneity, distinct function and prominent homeostatic proliferation. We propose a universal category system of T and NK cells based on distinct chemokine receptors, confirmed subsequently by phenotype, transcriptional factors and functionality. We also identified adaptive changes by the spleen and liver-derived monocyte and macrophage populations. Finally, we give a global glimpse on B cell and plasma cell subsets in human spleen and liver. We, therefore, reveal the heterogeneity and functional diversity of LrICs in human. This study presents comprehensively the landscape of LrICs and will enable further study on their roles in various human diseases.

ZINC TRANSPORTER5 and ZINC TRANSPORTER9 Function Synergistically in Zinc/Cadmium Uptake.

The elements Zinc (Zn) and cadmium (Cd) have similar chemical and physical properties, but contrasting physiological effects in higher organisms. In plants, Zn/Cd transport is mediated by various transporter proteins belonging to different families. In this study, we functionally characterized two Zn transporter genes in rice (Oryza sativa), ZINC TRANSPORTER5 (OsZIP5) and ZINC TRANSPORTER9 (OsZIP9), which are tandem duplicates and act synergistically in Zn/Cd uptake. Both genes encode plasma membrane-localized proteins with influx transporter activity. The expression profiles of OsZIP5 and OsZIP9 overlap in the root epidermis and respond to the local Zn status in the root. However, OsZIP9 is also regulated by systemic signals of Zn status from the shoot. OsZIP5 functions redundantly to OsZIP9, but has a relatively weaker effect. Plants with the knockout mutations oszip5, oszip9, or oszip5oszip9 show impaired Zn/Cd uptake. The decreased Zn/Cd levels and growth retardation in the oszip5 mutant are less severe than in the oszip9 mutant. However, the double mutant oszip5oszip9 showed an enhanced Zn deficiency phenotype compared with the single mutants, and few double-knockout plants were able to survive the entire growth cycle without excessive Zn supply. Transgenic plants overexpressing OsZIP9 had markedly enhanced Zn/Cd levels in the aboveground tissues and brown rice. The results of our study fill a gap in current knowledge of Zn uptake and improve our understanding of Zn/Cd accumulation in rice.