The compensatory role of T cells from lymph nodes in mice with splenectomy.

The spleen is a vital organ for the immune system, while splenectomy may be necessary for various reasons. However, there is limited research on the impact of splenectomy on T cell function in peripheral lymph nodes as a compensatory mechanism in preventing infections. This study aimed to investigate the characteristics and function of CD8+ and CD4+ T cells in different peripheral lymph nodes during viral infection using a well-established splenectomy model. The results revealed that splenectomy caused an increase in CD8+GP33+ T cells in the mesenteric lymph nodes (MLN). Moreover, we demonstrated that splenectomy resulted in an increase of effector KLRG1+ T cells in the MLN. Additionally, the number of CD4+ cytotoxic T cells (CD4 CTLs) was also elevated in the peripheral lymph nodes of mice with splenectomy. Surprisingly, aged mice exhibited a stronger compensatory ability than adult mice, as evidenced by an increase in effector CD8+ T cells in all peripheral lymph nodes. These findings provide compelling evidence that T cells in MLN play a crucial role in protecting individuals with splenectomy against viral infections. The study offers new insights into understanding the changes in the immune system of individuals with splenectomy and highlights the potential compensatory mechanisms involved by T cells in peripheral lymph nodes.

CD11b + CD43 hi Ly6C lo splenocyte-derived macrophages exacerbate liver fibrosis via spleen-liver axis.

BACKGROUND AND AIMS: Monocyte-derived macrophages (MoMFs), a dominant population of hepatic macrophages under inflammation, play a crucial role in liver fibrosis progression. The spleen serves as an extra monocyte reservoir in inflammatory conditions; however, the precise mechanisms of involvement of the spleen in the pathogenesis of liver fibrosis remain unclear. APPROACH AND RESULTS: By splenectomy and splenocyte transfusion, it was observed that splenic CD11b + cells accumulated intrahepatically as Ly6C lo MoMFs to exacerbate CCl 4 -induced liver fibrosis. The splenocyte migration into the fibrotic liver was further directly visualized by spleen-specific photoconversion with KikGR mice and confirmed by CD45.1 + /CD45.2 + spleen transplantation. Spleen-derived CD11b + cells purified from fibrotic livers were then annotated by single-cell RNA sequencing, and a subtype of CD11b + CD43 hi Ly6C lo splenic monocytes (sM-1s) was identified, which was markedly expanded in both spleens and livers of mice with liver fibrosis. sM-1s exhibited mature feature with high expressions of F4/80, produced much ROS, and manifested preferential migration into livers. Once recruited, sM-1s underwent sequential transformation to sM-2s (highly expressed Mif , Msr1 , Clec4d , and Cstb ) and then to spleen-derived macrophages (sMφs) with macrophage features of higher expressions of CX 3 CR1, F4/80, MHC class II, and CD64 in the fibrotic hepatic milieu. Furthermore, sM-2s and sMφs were demonstrated capable of activating hepatic stellate cells and thus exacerbating liver fibrosis. CONCLUSIONS: CD11b + CD43 hi Ly6C lo splenic monocytes migrate into the liver and shift to macrophages, which account for the exacerbation of liver fibrosis. These findings reveal precise mechanisms of spleen-liver axis in hepatic pathogenesis and shed light on the potential of sM-1 as candidate target for controlling liver diseases.

Assessment of association between the carotid web and dissection in spontaneous internal carotid artery dissection patients using vessel wall MRI.

BACKGROUND: Internal carotid artery dissection (ICAD) is the major cause of ischemic stroke in young to middle-aged people. Recognition of predisposing factors may facilitate in early individual risk prediction and expand treatment. PURPOSE: To evaluate the association between a carotid web and dissection in patients with ICAD using vessel wall magnetic resonance imaging (VW-MRI). MATERIAL AND METHODS: A retrospective study was conducted of 223 patients who underwent VW-MRI. Of these patients, 58 patients with craniocervical artery dissection (CCAD) (33 ICAD and 25 vertebrobasilar artery dissection [VBAD]) were included. The control group (n = 165) consisted of patients without arterial dissection who had undergone VW-MRI . The presence of a carotid web in the posterior aspect of carotid bulb was recorded. The distance between the carotid web and start of dissection in ICA was recorded. RESULTS: The presence of a carotid web showed a significant difference between the ICAD, VBAD, and control groups (19 [57.6%] vs. 5 [20%] vs. 36 [21.8%], respectively; P < 0.001). In multi-nominal analysis, the presence of a carotid web showed a significant difference between the ICAD and VBAD groups and the ICAD and control groups (P < 0.05), with odds ratios of 5.41 (95% confidence interval [CI]=1.634-17.973) and 4.81 (95% CI=2.176-10.651), respectively. Out of 19 ICAD patients with carotid web, 16 had occurrence of dissection in the C1 segment of the ICA with a mean distance of 1.91 ± 1.71 cm from the carotid web. CONCLUSION: Presence of a carotid web was more frequent in patients with ICAD. The carotid web may be one of the predisposing factors for development of dissection in patients with ICAD.

Detoxification mechanism of herbicide in Polypogon fugax and its influence on rhizosphere enzyme activities.

The excessive use of chemical herbicides has resulted in evolution of herbicide-resistant weeds. Cytochrome P450 monooxygenases (P450s) are vital detoxification enzymes for herbicide-resistant weeds. Herein, we confirmed a resistant (R) Polypogon fugax population showing resistance to quizalofop-p-ethyl, acetolactate synthase (ALS)-inhibiting herbicide pyroxsulam, and several other ACCase (acetyl-CoA carboxylase)-inhibiting herbicides. Molecular analysis revealed no target-site gene mutations in the R population. Foliar spraying with malathion clearly reversed the quizalofop-p-ethyl phytotoxicity. Higher level of quizalofop-p-ethyl degradation was confirmed in the R population using HPLC analysis. Subsequently, RNA-Seq transcriptome analysis indicated that the overexpression of CYP89A2 gene appeared to be responsible for reducing quizalofop-p-ethyl phytotoxicity. The molecular docking results supported a metabolic effect of CYP89A2 protein on most herbicides tested. Furthermore, we found that low doses of herbicides stimulated the rhizosphere enzyme activities in P. fugax and the increase of rhizosphere dehydrogenase of R population may be related to its resistance mechanism. In summary, our research has shown that metabolic herbicide resistance mediated by CYP89A2, contributes to quizalofop-p-ethyl resistance in P. fugax.

miR-3,178 contributes to the therapeutic action of baicalein against hepatocellular carcinoma cells via modulating HDAC10.

Hepatocellular carcinoma (HCC) is the most common type of hepatic malignancies with high mortality and poor prognosis. Baicalein, one of the major and bioactive flavonoids isolated from Scutellaria baicalensis Georgi, which is reported to have anti-proliferation effect in varying cancers, including HCC, whose underlying molecular mechanism is still largely unknown. In this study, we found that baicalein significantly inhibited proliferation and colony formation, blocked cell cycle, and promoted apoptosis in HCC cells MHCC-97H and SMMC-7721 in vitro and reduced tumor volume and weight in vivo. Increased microRNA (miR)-3,178 levels and decreased histone deacetylase 10 (HDAC10) expression were found in cells treated with baicalein and in patients' HCC tissues. HDAC10 was identified as a target gene of miR-3,178 by luciferase activity and western blot. Both baicalein treatment and overexpression of miR-3,178 could downregulate HDAC10 protein expression and inactivated AKT, MDM2/p53/Bcl2/Bax and FoxO3α/p27/CDK2/Cyclin E1 signal pathways. Not only that, knockdown of miR-3,178 could partly abolish the effects of baicalein and the restoration of HDAC10 could abated miR-3,178-mediated role in HCC cells. Collectively, baicalein inhibits cell viability, blocks cell cycle, and induces apoptosis in HCC cells by regulating the miR-3,178/HDAC10 pathway. This finding indicated that baicalein might be promising for treatment of HCC.

MS-Net: Learning to assess the malignant status of a lung nodule by a radiologist and her peers.

BACKGROUND: Automatically assessing the malignant status of lung nodules based on CTscan images can help reduce the workload of radiologists while improving their diagnostic accuracy. PURPOSE: Despite remarkable progress in the automatic diagnosis of pulmonary nodules by deep learning technologies, two significant problems remain outstanding. First, end-to-end deep learning solutions tend to neglect the empirical (semantic) features accumulated by radiologists and only rely on automatic features discovered by neural networks to provide the final diagnostic results, leading to questionable reliability, and interpretability. Second, inconsistent diagnosis between radiologists, a widely acknowledged phenomenon in clinical settings, is rarely examined and quantitatively explored by existing machine learning approaches. This paper solves these problems. METHODS: We propose a novel deep neural network called MS-Net, which comprises two sequential modules: A feature derivation and initial diagnosis module (FDID), followed by a diagnosis refinement module (DR). Specifically, to take advantage of accumulated empirical features and discovered automatic features, the FDID model of MS-Net first derives a range of perceptible features and provides two initial diagnoses for lung nodules; then, these results are fed to the subsequent DR module to refine the diagnoses further. In addition, to fully consider the individual and panel diagnosis opinions, we propose a new loss function called collaborative loss, which can collaboratively optimize the individual and her peers' opinions to provide a more accurate diagnosis. RESULTS: We evaluate the performance of the proposed MS-Net on the Lung Image Database Consortium image collection (LIDC-IDRI). It achieves 92.4% of accuracy, 92.9% of sensitivity, and 92.0% of specificity when panel labels are the ground truth, which is superior to other state-of-the-art diagnosis models. As a byproduct, the MS-Net can automatically derive a range of semantic features of lung nodules, increasing the interpretability of the final diagnoses. CONCLUSIONS: The proposed MS-Net can provide an automatic and accurate diagnosis of lung nodules, meeting the need for a reliable computer-aided diagnosis system in clinical practice.

Dynamic Changes in Serum Cytokine Profile in Rats with Severe Acute Pancreatitis.

Background and Objectives: Most published research has only investigated a single timepoint after the onset of severe acute pancreatitis (SAP), meaning that they have been unable to observe the relationship between the dynamic changes in cytokines and SAP progression. In this study, we attempted to reveal the relationship between dynamic changes in cytokine expression levels and SAP disease progression and the relationship between cytokines, using continuous large-scale cytokine detection. Materials and Methods: Seventy rats were randomly assigned to control (Con), sham operation (SO) and SAP groups. The SAP group was randomly allocated to five subgroups at 3, 6, 9, 12 and 15 h after the operation. In the SAP group, 5% sodium taurocholate was injected retrograde into the pancreatic bile duct. Animals in the SO group received a similar incision, a turning over of the pancreas. Control animals did not receive any treatment. We observed the survival, ascites fluid amount, pancreatic histopathological scores and serum amylase activity of SAP rats. We used the cytokine microarray to simultaneously detect 90 cytokines and the dynamic changes in one experiment and to analyze the correlation between cytokine expression and disease progression. Results: The mortality of SAP rats increased with an increase in time. Serum amylase activity, pancreatic histopathological scores and ascites fluid amount were time-dependent. Compared with normal rats, 69 cytokines in SAP rats were significantly changed for at least one timepoint, and 49 cytokines were significantly changed at different timepoints after SAP induction. The changes in inflammatory cytokines were significantly upregulated at 6 and 9 h and 12 h and then significantly decreased. Conclusions: The trend of cytokine expression in SAP rats was not consistent with the disease progression. The cytokine-cytokine receptor interaction and MAPK signal's dominant cytokines were always highly expressed at various time points over the course of SAP.

Chronic stress inhibits testosterone synthesis in Leydig cells through mitochondrial damage via Atp5a1.

Stress is one of the leading causes of male infertility, but its exact function in testosterone synthesis has scarcely been reported. We found that adult male rats show a decrease in bodyweight, genital index and serum testosterone level after continual chronic stress for 21 days. Two-dimensional gel electrophoresis (2-DE) and MALDI-TOF-MS analysis identified 10 differentially expressed proteins in stressed rats compared with controls. A strong protein interaction network was found to be centred on Atp5a1 among these proteins. Atp5a1 expression significantly decreased in Leydig cells after chronic stress. Transfection of Atp5a1 siRNAs decreased StAR, CYP11A1, and 17ß-HSD expression by damaging the structure of mitochondria in TM3 cells. This study confirmed that chronic stress plays an important role in testosterone synthesis by regulating Atp5a1 expression in Leydig cells.

Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis.

BACKGROUND & AIMS: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction. METHODS: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. RESULTS: Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses. CONCLUSIONS: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. LAY SUMMARY: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.

COVID-19 epidemic in New York City: development of an age group-specific mathematical model to predict the outcome of various vaccination strategies.

BACKGROUND: Since December 14, 2020, New York City (NYC) has started the first batch of COVID-19 vaccines. However, the shortage of vaccines is currently an inevitable problem. Therefore, optimizing the age-specific COVID-19 vaccination is an important issue that needs to be addressed as a priority. OBJECTIVE: Combined with the reported COVID-19 data in NYC, this study aimed to construct a mathematical model with five age groups to estimate the impact of age-specific vaccination on reducing the prevalence of COVID-19. METHODS: We proposed an age-structured mathematical model and estimated the unknown parameters based on the method of Markov Chain Monte Carlo (MCMC). We also calibrated our model by using three different types of reported COVID-19 data in NYC. Moreover, we evaluated the reduced cumulative number of deaths and new infections with different vaccine allocation strategies. RESULTS: Compared with the current vaccination strategy in NYC, if we gradually increased the vaccination coverage rate for only one age groups from March 1, 2021 such that the vaccination coverage rate would reach to 40% by June 1, 2021, then as of June 1, 2021, the cumulative deaths in the 75-100 age group would be reduced the most, about 72 fewer deaths per increased 100,000 vaccinated individuals, and the cumulative new infections in the 0-17 age group would be reduced the most, about 21,591 fewer new infections per increased 100,000 vaccinated individuals. If we gradually increased the vaccination coverage rate for two age groups from March 1, 2021 such that the vaccination coverage rate would reach to 40% by June 1, 2021, then as of June 1, 2021, the cumulative deaths in the 65-100 age group would be reduced the most, about 36 fewer deaths per increased 100,000 vaccinated individuals, and the cumulative new infections in the 0-44 age group would be reduced the most, about 17,515 fewer new infections per increased 100,000 vaccinated individuals. In addition, if we had an additional 100,000 doses of vaccine for 0-17 and 75-100 age groups as of June 1, 2021, then the allocation of 80% to the 0-17 age group and 20% to the 75-100 age group would reduce the maximum numbers of new infections and deaths simultaneously in NYC. CONCLUSIONS: The COVID-19 burden including deaths and new infections would decrease with increasing vaccination coverage rate. Priority vaccination to the elderly and adolescents would minimize both deaths and new infections.

The Evolution and Disparities of Online Attitudes Toward COVID-19 Vaccines: Year-long Longitudinal and Cross-sectional Study.

BACKGROUND: Due to the urgency caused by the COVID-19 pandemic worldwide, vaccine manufacturers have to shorten and parallel the development steps to accelerate COVID-19 vaccine production. Although all usual safety and efficacy monitoring mechanisms remain in place, varied attitudes toward the new vaccines have arisen among different population groups. OBJECTIVE: This study aimed to discern the evolution and disparities of attitudes toward COVID-19 vaccines among various population groups through the study of large-scale tweets spanning over a whole year. METHODS: We collected over 1.4 billion tweets from June 2020 to July 2021, which cover some critical phases concerning the development and inoculation of COVID-19 vaccines worldwide. We first developed a data mining model that incorporates a series of deep learning algorithms for inferring a range of individual characteristics, both in reality and in cyberspace, as well as sentiments and emotions expressed in tweets. We further conducted an observational study, including an overall analysis, a longitudinal study, and a cross-sectional study, to collectively explore the attitudes of major population groups. RESULTS: Our study derived 3 main findings. First, the whole population's attentiveness toward vaccines was strongly correlated (Pearson r=0.9512) with official COVID-19 statistics, including confirmed cases and deaths. Such attentiveness was also noticeably influenced by major vaccine-related events. Second, after the beginning of large-scale vaccine inoculation, the sentiments of all population groups stabilized, followed by a considerably pessimistic trend after June 2021. Third, attitude disparities toward vaccines existed among population groups defined by 8 different demographic characteristics. By crossing the 2 dimensions of attitude, we found that among population groups carrying low sentiments, some had high attentiveness ratios, such as males and individuals aged ≥40 years, while some had low attentiveness ratios, such as individuals aged ≤18 years, those with occupations of the 3rd category, those with account age <5 years, and those with follower number <500. These findings can be used as a guide in deciding who should be given more attention and what kinds of help to give to alleviate the concerns about vaccines. CONCLUSIONS: This study tracked the year-long evolution of attitudes toward COVID-19 vaccines among various population groups defined by 8 demographic characteristics, through which significant disparities in attitudes along multiple dimensions were revealed. According to these findings, it is suggested that governments and public health organizations should provide targeted interventions to address different concerns, especially among males, older people, and other individuals with low levels of education, low awareness of news, low income, and light use of social media. Moreover, public health authorities may consider cooperating with Twitter users having high levels of social influence to promote the acceptance of COVID-19 vaccines among all population groups.

Hepatoprotective effect of apolipoprotein A4 against carbon tetrachloride induced acute liver injury through mediating hepatic antioxidant and inflammation response in mice.

Apolipoprotein A4 (ApoA4) regulates lipid and glucose metabolism and exerts anti-inflammatory effects in atherogenesis and colitis. The present study explored the presumed protective role of ApoA4 in carbon tetrachloride (CCl4)-induced acute liver injury (ALI) in mice. The ALI model in wild type (WT), ApoA4 knock-out (ApoA4-KO) and ApoA4 transgenic (ApoA4-TG) mice was induced by a single intraperitoneal administration of CCl4. Liver and blood were harvested from mice to assess liver functions, immunohistological changes, immune cell populations and cytokine profiles. ApoA4 deficiency aggravated, and ApoA4 overexpression alleviated CCl4-inflicted liver damage by controlling levels of anti-oxidant enzymes. ApoA4 deletion increased the recruitment of monocytes/macrophages into the injured liver and upregulated the plasma levels of IL-6, TNF-α and MCP-1, but lower IL-10 and IFN-γ. ApoA4 over-expression rescued this effect and resulted in lower percentages of monocytes/macrophages and dendritic cells, the ratio of blood pro-inflammatory to anti-inflammatory monocytes and reduced plasma concentrations of IL-6, but enhanced IL-10 and IFN-γ. We propose ApoA4 as a potential new therapeutic target for the management of liver damage.

MiR-3663-3p participates in the anti-hepatocellular carcinoma proliferation activity of baicalein by targeting SH3GL1 and negatively regulating EGFR/ERK/NF-κB signaling.

Baicalein is a purified flavonoid that exhibits anticancer effects in hepatocellular carcinoma (HCC). However, its underlying molecular mechanisms remain largely unclear. In this study, we found that baicalein inhibited HCC cell growth, induced apoptosis, and blocked cell cycle arrest at the S phase in vitro, as well as reduced HCC tumor volume and weight in vivo. Quantitative reverse transcriptase-PCR (qRT-PCR) results suggested that miR-3663-3p was downregulated in HCC tissues. After baicalein treatment, miR-3663-3p expression was upregulated in HCC cells. Transfection of miR-3663-3p suppressed HCC cell proliferation and colony formation, increased the proportion of apoptotic cells in vitro, and reduced the volume and weight of tumors in vivo. The results of dual-luciferase reporter assay showed that miR-3663-3p could directly bind to the 3'-UTR of SH3GL1. SH3GL1 overexpression partly reduced the growth-inhibiting effect of miR-3663-3p. Both baicalein treatment and miR-3663-3p overexpression downregulated the expression of SH3GL1 and inactivated the Erk1/2, p-NF-κB/p65, and EGFR signaling pathways. Overall, our data suggest that baicalein may act as a novel HCC suppressor, and that the miR-3663-3p/SH3GL1/EGFR/ERK/NF-κB pathway plays a vital role in HCC progression. Thus, baicalein treatment or miR-3663-3p induction may be a promising strategy for HCC therapy.

Protective Role of C3aR (C3a Anaphylatoxin Receptor) Against Atherosclerosis in Atherosclerosis-Prone Mice.

OBJECTIVE: Emerging evidence suggests that C3aR (C3a anaphylatoxin receptor) signaling has protective roles in various inflammatory-related diseases. However, its role in atherosclerosis has been unknown. The purpose of the study was to investigate the possible protective role of C3aR in aortic atherosclerosis and explore molecular and cellular mechanisms involved in the protection. Approach and Results: C3ar-/-/Apoe-/- mice were generated by cross-breeding of atherosclerosis-prone Apoe-/- mice and C3ar-/- mice. C3ar-/-/Apoe-/- mice and Apoe-/- mice (as a control) underwent high-fat diet for 16 weeks were assessed for (1) atherosclerotic plaque burden, (2) aortic tissue inflammation, (3) recruitment of CD11b+ leukocytes into atherosclerotic lesions, and (4) systemic inflammatory responses. Compared with Apoe-/- mice, C3ar-/-/Apoe-/- mice developed more severe atherosclerosis. In addition, C3ar-/-/Apoe-/- mice have increased local production of proinflammatory mediators (eg, CCL2 [chemokine (C-C motif) ligand 2], TNF [tumor necrosis factor]-α) and infiltration of monocyte/macrophage in aortic tissue, and their lesional macrophages displayed an M1-like phenotype. Local pathological changes were associated with enhanced systemic inflammatory responses (ie, elevated plasma levels of CCL2 and TNF-α, increased circulating inflammatory cells). In vitro analyses using peritoneal macrophages showed that C3a stimulation resulted in upregulation of M2-associated signaling and molecules, but suppression of M1-associated signaling and molecules, supporting the roles of C3a/C3aR axis in mediating anti-inflammatory response and promoting M2 macrophage polarization. CONCLUSIONS: Our findings demonstrate a protective role for C3aR in the development of atherosclerosis and suggest that C3aR confers the protection through C3a/C3aR axis-mediated negative regulation of proinflammatory responses and modulation of macrophage toward the anti-inflammatory phenotype.

High hepatitis C virus cure rates with approved interferon-free direct-acting antivirals among diverse mainland Chinese patients including genotypes 3a and 3b.

BACKGROUND AND AIM: Globally, China has the highest chronic hepatitis C (CHC) burden, but its real-world direct-acting antiviral (DAA) data are limited. Our aim is to investigate the real-world outcome of China Food and Drug Administration-approved DAA therapies across mainland China including those with genotype (GT) 3. METHODS: The REAL-C is a multinational real-world interferon-free DAA-treated CHC registry of several mainland China and other Asian centers. We evaluated the sustained virological response rate 12 weeks after end of treatment (SVR12), adverse events, and treatment effect on liver function and fibrosis (fibrosis-4 index). RESULTS: We analyzed 859 DAA-treated CHC patients (6/1/2017-5/30/2019) from 12 mainland China centers (three municipalities and nine provinces): median age 52, 49.9% male, 33.1% cirrhosis, 95% treatment naïve, and 2.5% HBsAg+ . The most common GT was GT1b (523, 62.2%), followed by GT2a (156, 18.5%), GT3b (74, 8.8%), GT3a (41, 4.9%), and GT6 (37, 4.4%). SVR12 rates were 98.0% overall (95% confidence interval 96.9-98.8%), 98.1% for GT1b, 96.8% GT2a, 100% GT3a, 97.3% GT3b, and 100% GT6. Baseline cirrhosis and male sex but not prior treatment history, renal dysfunction, age, and GTs were associated with SVR12. For both cirrhotic and non-cirrhotic patients, there were significant improvement in liver function tests, alpha fetoprotein, and fibrosis-4 index with SVR12. Serious adverse events were rare (1.1%) with only nine patients discontinuing therapy prematurely and anemia being the most common adverse event (13.1%, mostly with ribavirin). CONCLUSIONS: In real-world Chinese patients with diverse GTs, Chinese Food and Drug Administration-approved interferon-free DAAs were well tolerated, provided high cure rates (98.0% overall) including GT3a/3b, and led to improvement of liver function.

Understanding Concerns, Sentiments, and Disparities Among Population Groups During the COVID-19 Pandemic Via Twitter Data Mining: Large-scale Cross-sectional Study.

BACKGROUND: Since the beginning of the COVID-19 pandemic in late 2019, its far-reaching impacts have been witnessed globally across all aspects of human life, such as health, economy, politics, and education. Such widely penetrating impacts cast significant and profound burdens on all population groups, incurring varied concerns and sentiments among them. OBJECTIVE: This study aims to identify the concerns, sentiments, and disparities of various population groups during the COVID-19 pandemic through a cross-sectional study conducted via large-scale Twitter data mining infoveillance. METHODS: This study consisted of three steps: first, tweets posted during the pandemic were collected and preprocessed on a large scale; second, the key population attributes, concerns, sentiments, and emotions were extracted via a collection of natural language processing procedures; third, multiple analyses were conducted to reveal concerns, sentiments, and disparities among population groups during the pandemic. Overall, this study implemented a quick, effective, and economical approach for analyzing population-level disparities during a public health event. The source code developed in this study was released for free public use at GitHub. RESULTS: A total of 1,015,655 original English tweets posted from August 7 to 12, 2020, were acquired and analyzed to obtain the following results. Organizations were significantly more concerned about COVID-19 (odds ratio [OR] 3.48, 95% CI 3.39-3.58) and expressed more fear and depression emotions than individuals. Females were less concerned about COVID-19 (OR 0.73, 95% CI 0.71-0.75) and expressed less fear and depression emotions than males. Among all age groups (ie, ≤18, 19-29, 30-39, and ≥40 years of age), the attention ORs of COVID-19 fear and depression increased significantly with age. It is worth noting that not all females paid less attention to COVID-19 than males. In the age group of 40 years or older, females were more concerned than males, especially regarding the economic and education topics. In addition, males 40 years or older and 18 years or younger were the least positive. Lastly, in all sentiment analyses, the sentiment polarities regarding political topics were always the lowest among the five topics of concern across all population groups. CONCLUSIONS: Through large-scale Twitter data mining, this study revealed that meaningful differences regarding concerns and sentiments about COVID-19-related topics existed among population groups during the study period. Therefore, specialized and varied attention and support are needed for different population groups. In addition, the efficient analysis method implemented by our publicly released code can be utilized to dynamically track the evolution of each population group during the pandemic or any other major event for better informed public health research and interventions.

Silencing of long noncoding RNA HOXD-AS1 inhibits proliferation, cell cycle progression, migration and invasion of hepatocellular carcinoma cells through MEK/ERK pathway.

Accumulating findings reveal that long noncoding RNAs (lncRNAs) as crucial regulatory molecules serve vital functions in the progression of hepatocellular carcinoma (HCC). This study aims to investigate the biological roles and mechanisms of lncRNA HOXD cluster antisense RNA 1 (HOXD-AS1) in HCC cells based on transcriptome analysis. The Cancer Genome Atlas data analysis and experimental validation showed that HOXD-AS1 was increased in HCC tissues/cell lines and positively relevant to histologic grade. The subcellular localization results indicated HOXD-AS1 was dispersed both in the nucleus as well as the cytoplasm of HCC cells. In vitro loss-of-function experiments revealed that silencing of HOXD-AS1 could dramatically suppress the proliferation, migration, and invasion, and induce S or/and G2/M phase cell cycle arrest as well as apoptosis of Bel-7402 and MHCC97H cells accompanying the changes in expression levels of cyclin B1, cyclin D1, BCL-2, BAX, and MMP2. In vivo assay also showed that HOXD-AS1 silencing could markedly reduce xenograft tumor volume and weight of HCC cells. Transcriptome and bioinformatic analysis indicated that a total of 1103 genes were significantly altered by HOXD-AS1 silencing, of which 132 genes exhibited a significant correlation with HOXD-AS1 expression in HCC tissues. Gene Ontology (GO) enrichment analysis revealed differentially expressed genes were remarkably enriched in several cancer-related biological processes (cell proliferation, cell cycle, apoptosis, migration, angiogenesis, and hypoxic response). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that HOXD-AS1 has the potential to affect p53, tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK) pathway, and Western blot results further validated that HOXD-AS1 silencing could inhibit the MEK/ERK pathway in Bel-7402 cells. Collectively, HOXD-AS1, as an oncogenic lncRNA, might exert crucial functions in HCC progression and serve as a potential diagnostic biomarker and therapeutic target for HCC.

Ring1 promotes the transformation of hepatic progenitor cells into cancer stem cells through the Wnt/ß-catenin signaling pathway.

The proliferation of hepatic progenitor cells (HPCs) is observed in reactive conditions of the liver and primary liver cancers. Ring1 as a member of polycomb-group proteins which play vital roles in carcinogenesis and stem cell self-renewal was increased in HCC patients and promoted proliferation and survival of cancer cell by degrading p53. However, the mechanisms of Ring1 driving the progression of hepatocarcinogenesis have not been elucidated. In this study, forced expression Ring1 and Ring1 siRNA lentiviral vectors were utilized to stably overexpression and silence Ring1 in HPC cell line (WB-F344), respectively. Our finding indicated that overexpression of Ring1 in HPCs promoted colony formation, cell multiplication, and invasion in vitro, conversely depletion of Ring1 repressed the biological functions of HPCs relative to controls. The expression of ß-catenin was upregulated in the HPCs with overexpression of Ring1, and the correlation analysis also showed that ß-catenin and Ring1 had a significant correlation in the liver cancer tissues and adjacent tissues. The activation of the Wnt/ß-catenin signaling pathway significantly increased the expression of liver cancer stem cells related (LCSCs)-related molecular markers CD90 and EpCAM, which led to the transformation of HPCs into LCSCs. Most importantly, the injection of HPCs with overexpressed Ring1 into the subcutaneous of nude mice leads to the formation of poorly differentiated HCC neoplasm. Our findings elucidate that overexpression of Ring1 the activated Wnt/ß-catenin signaling pathway and drove the transformation of HPCs into cancer stem cell-like cells, suggesting Ring1 has extraordinary potential in early diagnosis of HCC.

A New Role for the Spleen: Aggravation of the Systemic Inflammatory Response in Rats with Severe Acute Pancreatitis.

Little is known about the role of the spleen in mediating systemic inflammatory responses in severe acute pancreatitis (SAP). We investigated the role played by the spleen in rats after SAP induction. Splenectomy was performed at designated time points after SAP induction. Pancreatic tissue and serum samples were collected and subjected to histologic, immunohistochemical, and immunologic analyses. After SAP induction, the splenic immune response was enhanced during SAP progression, as shown by the increased diameter of the splenic periarterial lymphatic sheath and the thickness of the splenic marginal zone. Rats with splenectomy developed acute pancreatitis more slowly than rats without splenectomy. In addition, pancreatic tissues of rats with splenectomy contained lower levels of serum amylase, tumor necrosis factor-α, and IL-6 and exhibited less acinar cell death, leukocyte infiltration, and interstitial edema than those of rats without splenectomy. Compared with splenectomy alone, cotreatment with splenectomy and the administration of splenic cells originating from a rat with SAP 12 hours after induction increased systemic inflammation in SAP rats. Splenic factors exacerbated SAP-associated liver and lung injury and accentuated intestinal mucosal barrier dysfunction. Splenectomy altered the serum cytokine profile in rats with SAP. In a rat model of SAP, the spleen exacerbated the systematic inflammatory responses and injury to multiple organs, indicating a new role for the spleen in SAP.

Concordance between treatment recommendations provided by IBM Watson for Oncology and a multidisciplinary tumor board for breast cancer in China.

OBJECTIVE: Watson for Oncology (WFO), an artificial intelligence from IBM Corporation, can provide a treatment plan by analyzing patient's disease characteristics. The present study was performed to examine the concordance between treatment recommendations proposed by WFO and the multidisciplinary tumor board at our center. The aim was to explore the feasibility of using WFO for breast cancer cases in China and to ascertain the ways to make WFO more suitable for Chinese patients with breast cancer. METHODS: Data from 302 breast cancer patients treated at the Second Affiliated Hospital of Xi'an Jiaotong University between October 2016 and February 2018 was retrieved and retrospectively analyzed by WFO. The recommendations were divided into 'recommended', 'considered' and 'not recommended' groups. Results were considered concordant when oncologists' recommendations were categorized as 'recommended' or 'for consideration' by WFO. RESULTS: The concordance rate of 200 subjects with postoperative adjuvant therapy was 77%. However, the rate was 27.5% in the remaining 102 cases with metastatic disease receiving either first-line or no treatment. Further analysis demonstrated that inconsistencies were mainly due to different choices of chemotherapy regimens. Subgroup study indicates that tumor stage, receptor status and age also had influences at the concordance rate. CONCLUSION: The results of this study suggest that WFO is a promising artificial intelligence system for the treatment of breast cancer. These findings can also serve as a reference framework for the inclusion of artificial intelligence in the ongoing medical reform in China.