5-HT-treated mouse B cells alleviate ulcerative colitis via RIPK1: Insights from proteomic and phosphoproteomic analyses.

5-hydroxytryptamine (5-HT) exerts various physiological effects on the intestine through different signaling pathways and molecular transmission mechanisms, including pro- and anti-inflammatory effects. Adoptive transfer of regulatory B cells (Bregs) into colitis mice has exhibited significant therapeutic benefits. We aimed to elucidate the mechanism through which 5-HT-treated B cells alleviate ulcerative colitis. To this end, we analyzed the proteomic and phosphoproteomic profiles of 5-HT-stimulated B cells from naïve mice. We identified 3124 phosphorylation sites in proteins via tandem mass tagging and found 110 differential peptides after protein phosphorylation. Furthermore, we obtained three differential proteins, RIPK1, ATXN2l, and Q8C5K5 through integration of both proteomic datasets. We discovered and validated that 5-HT binds to 5-HT7R and increases the expression of RIPK1 in B cells. We propose a theoretical and experimental basis for further research on the RIPK1 signaling pathway, kinase prediction, and phosphorylation sites in ulcerative colitis. SIGNIFICANCE: Some researchers demonstrated that 5-HT can effectively suppress colitis through a variety of molecular mechanisms. Our study discovered and consistently validated the 5-HT/5-HT7R/RIPK1 pathway, further clarifying the molecular mechanism through which 5-HT stimulates B cells to alleviate intestinal inflammation.

5-HT induces regulatory B cells in fighting against inflammation-driven ulcerative colitis.

Serotonin (5-hydroxytryptamine or 5-HT) is a neuroendocrine peptide endowed with immunomodulatory functions. Regulatory B cells (Bregs) play an important role in maintaining intestinal immune homeostasis. We analyzed the differences of 5-HT and Bregs between peripheral blood of ulcerative colitis (UC) and healthy controls (HC). Besides, 5-HT-treated B cells were adoptively transferred into colitis mice to elucidate the role of 5-HT in regulating Bregs. The level of serum 5-HT and IL-10 in UC patients was lower and both were negatively correlated with disease activity. 5-HT7 receptor (5-HT7R) was higher expressed on Bregs in UC. 5-HT promoted IL-10 production in Bregs through the activation of STAT3. And adoptive transfer of 5-HT-treated B cells alleviated intestinal inflammation via inducing IL-10-producing B cells in mice. Our results suggest that 5-HT/5-HT7R signaling pathway facilitate functional Bregs in constraining inflammation in UC, which may be a new potential prospect in the treatment of UC.

Conventional and artificial intelligence-based computed tomography and magnetic resonance imaging quantitative techniques for non-invasive liver fibrosis staging.

Chronic liver disease (CLD) ultimately develops into liver fibrosis and cirrhosis and is a major public health problem globally. The assessment of liver fibrosis is important for patients with CLD for prognostication, treatment decisions, and surveillance. Liver biopsies are traditionally performed to determine the stage of liver fibrosis. However, the risks of complications and technical limitations restrict their application to screening and sequential monitoring in clinical practice. CT and MRI are essential for evaluating cirrhosis-associated complications in patients with CLD, and several non-invasive methods based on them have been proposed. Artificial intelligence (AI) techniques have also been applied to stage liver fibrosis. This review aimed to explore the values of conventional and AI-based CT and MRI quantitative techniques for non-invasive liver fibrosis staging and summarized their diagnostic performance, advantages, and limitations.

Novel, high accuracy models for hepatocellular carcinoma prediction based on longitudinal data and cell-free DNA signatures.

BACKGROUND & AIMS: Current hepatocellular carcinoma (HCC) risk scores do not reflect changes in HCC risk resulting from liver disease progression/regression over time. We aimed to develop and validate two novel prediction models using multivariate longitudinal data, with or without cell-free DNA (cfDNA) signatures. METHODS: A total of 13,728 patients from two nationwide multicenter prospective observational cohorts, the majority of whom had chronic hepatitis B, were enrolled. aMAP score, as one of the most promising HCC prediction models, was evaluated for each patient. Low-pass whole-genome sequencing was used to derive multi-modal cfDNA fragmentomics features. A longitudinal discriminant analysis algorithm was used to model longitudinal profiles of patient biomarkers and estimate the risk of HCC development. RESULTS: We developed and externally validated two novel HCC prediction models with a greater accuracy, termed aMAP-2 and aMAP-2 Plus scores. The aMAP-2 score, calculated with longitudinal data on the aMAP score and alpha-fetoprotein values during an up to 8-year follow-up, performed superbly in the training and external validation cohorts (AUC 0.83-0.84). The aMAP-2 score showed further improvement and accurately divided aMAP-defined high-risk patients into two groups with 5-year cumulative HCC incidences of 23.4% and 4.1%, respectively (p = 0.0065). The aMAP-2 Plus score, which incorporates cfDNA signatures (nucleosome, fragment and motif scores), optimized the prediction of HCC development, especially for patients with cirrhosis (AUC 0.85-0.89). Importantly, the stepwise approach (aMAP -> aMAP-2 -> aMAP-2 Plus) stratified patients with cirrhosis into two groups, comprising 90% and 10% of the cohort, with an annual HCC incidence of 0.8% and 12.5%, respectively (p <0.0001). CONCLUSIONS: aMAP-2 and aMAP-2 Plus scores are highly accurate in predicting HCC. The stepwise application of aMAP scores provides an improved enrichment strategy, identifying patients at a high risk of HCC, which could effectively guide individualized HCC surveillance. IMPACT AND IMPLICATIONS: In this multicenter nationwide cohort study, we developed and externally validated two novel hepatocellular carcinoma (HCC) risk prediction models (called aMAP-2 and aMAP-2 Plus scores), using longitudinal discriminant analysis algorithm and longitudinal data (i.e., aMAP and alpha-fetoprotein) with or without the addition of cell-free DNA signatures, based on 13,728 patients from 61 centers across mainland China. Our findings demonstrated that the performance of aMAP-2 and aMAP-2 Plus scores was markedly better than the original aMAP score, and any other existing HCC risk scores across all subsets, especially for patients with cirrhosis. More importantly, the stepwise application of aMAP scores (aMAP -> aMAP-2 -> aMAP-2 Plus) provides an improved enrichment strategy, identifying patients at high risk of HCC, which could effectively guide individualized HCC surveillance.

Systemic inflammatory regulators and risk of acute-on-chronic liver failure: A bidirectional mendelian-randomization study.

Inflammation plays a role in the pathogenesis of acute-on-chronic liver failure (ACLF), however, whether there is a causal relationship between inflammation and ACLF remains unclear. A two-sample Mendelian randomization (MR) approach was used to investigate the causal relationship between systemic inflammatory regulators and ACLF. The study analyzed 41 cytokines and growth factors from 8,293 individuals extracted from a genome-wide association study (GWAS) meta-analysis database involving 253 ACLF cases and 456,095 controls. Our results showed that lower stem cell factor (SCF) levels, lower basic fibroblast growth factor (bFGF) levels and higher Interleukin-13 (IL-13) levels were associated with an increased risk of ACLF (OR = 0.486, 95% CI = 0.264-0.892, p = 0.020; OR = 0.323, 95% CI = 0.107-0.972, p = 0.044; OR = 1.492, 95% CI = 1.111-2.004, p = 0.008, respectively). In addition, genetically predicted ACLF did not affect the expression of systemic inflammatory regulators. Our results indicate that cytokines play a crucial role in the pathogenesis of ACLF. Further studies are needed to determine whether these biomarkers can be used to prevent and treat ACLF.

Effectiveness of inactivated COVID-19 vaccines against mild disease, pneumonia, and severe disease among persons infected with SARS-CoV-2 Omicron variant: real-world study in Jilin Province, China.

It is critical to determine the real-world performance of vaccines against coronavirus disease 2019 (COVID-19) so that appropriate treatments and policies can be implemented. There was a rapid wave of infections by the Omicron variant in Jilin Province (China) during spring 2022. We examined the effectiveness of inactivated vaccines against Omicron using real-world data from this epidemic. This retrospective case-case study of vaccine effectiveness (VE) examined infected patients who were quarantined and treated from April 16 to June 8, 2022 and responded to an electronic questionnaire. Data were analyzed by univariable and multivariable analyses. A total of 2968 cases with SARS-CoV-2 infections (asymptomatic: 1061, mild disease: 1763, pneumonia: 126, severe disease: 18) were enrolled in the study. Multivariable regression indicated that the risk for pneumonia or severe disease was greater in those who were older or had underlying diseases, but was less in those who received COVID-19 vaccines. Relative to no vaccination, VE against the composite of pneumonia and severe disease was significant for those who received 2 doses (60.1%, 95%CI: 40.0%, 73.5%) or 3 doses (68.1%, 95%CI: 44.6%, 81.7%), and VE was similar in the subgroups of males and females. However, VE against the composite of all three classes of symptomatic diseases was not significant overall, nor after stratification by sex. There was no statistical difference in the VE of vaccines from different manufacturers. The inactivated COVID-19 vaccines protected patients against pneumonia and severe disease from Omicron infection, and booster vaccination enhanced this effect.

Association of Nirmatrelvir/Ritonavir Treatment on Upper Respiratory Severe Acute Respiratory Syndrome Coronavirus 2 Reverse Transcription-Polymerase Chain Reaction (SARS-Cov-2 RT-PCR) Negative Conversion Rates Among High-Risk Patients With Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Acceleration of negative respiratory conversion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19) might reduce viral transmission. Nirmatrelvir/ritonavir is a new antiviral agent recently approved for treatment of COVID-19 that has the potential to facilitate negative conversion. METHODS: A cohort of hospitalized adult patients with mild-to-moderate COVID-19 who had a high risk for progression to severe disease were studied. These patients presented with COVID-19 symptoms between 5 March and 5 April 2022. The time from positive to negative upper respiratory reverse transcription-polymerase chain reaction (RT-PCR) conversion was assessed by Kaplan-Meier plots and Cox proportional hazards regression with the adjustment for patients' baseline demographic and clinical characteristics. RESULTS: There were 258 patients treated with nirmatrelvir/ritonavir and 224 nontreated patients who had mild-to-moderate COVID-19. The median (interquartile range) time for patients who converted from positive to negative RT-PCR was 10 days (7-12 days) in patients treated ≤5 days after symptom onset and 17 days (12-21 days) in nontreated patients. The proportions of patients with a negative conversion at day 15 were 89.7% and 42.0% in treated patients and nontreated patients, corresponding to a hazard ratio of 4.33 (95% confidence interval, 3.31-5.65). Adjustment for baseline differences between the groups had little effect on the association. Subgroup analysis on treated patients suggests that time to negative conversion did not vary with the patients' baseline characteristics. CONCLUSIONS: This cohort study of high-risk patients with mild-to-moderate COVID-19 found an association between nirmatrelvir/ritonavir treatment and accelerated negative RT-PCR respiratory SARS-CoV-2 conversion that might reduce the risk of viral shedding and disease transmission.

Case Report: A rare case of young adult progressive familial intrahepatic cholestasis-type 3 with a novel heterozygous pathogenic variant of ABCB4.

Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a rare autosomal recessive disorder with poor prognosis. It is caused by pathogenic variants of the ATP binding cassette subfamily B member 4 (ABCB4) gene and usually progresses from chronic cholestasis with or without jaundice to portal hypertension and end-stage liver disease within the first to second decade of life. Few reported PFIC-3 patients presented with atypical clinical symptoms, therefore, often misdiagnosed if without family history. Herein, we report a 16-year-old male who was admitted to our hospital due to acute episodes of jaundice and intense pruritus, subsequently progressed to end-stage liver disease. Laboratory examinations showed no evidence of liver injury caused by viral, autoimmune, drug or liver tumors. Ursodeoxycholic acid and dexamethasone did not relieve his symptoms and he underwent liver transplantation successfully. Targeted next-generation sequencing identified that the patient was a compound heterozygote for two missense mutations (c.959C > T/c.1429C > A) in the ABCB4 gene. The mutation c.1429C > A (p.Q477K) is a novel heterozygous mutation. We constructed a three-dimensional model of this novel pathogenic variant using the SWISS MODEL program and found that the patient's ABCB4 protein is an ATP hydrolysis deficient mutant. The postoperative pathological diagnosis showed intrahepatic cholestasis with progression to cirrhosis. Negative liver tissue immunohistochemistry of MDR3 was found in the explanted liver. The patient was diagnosed with PFIC-3, and his symptoms improved dramatically with liver transplantation. In conclusion, for young patients with acute cholestasis, pruritus, jaundice, growth retardation, and enlargement of the liver and spleen, the possibility of inherited metabolic liver diseases should be considered, detailed medical and family history should be collected, and metabolic screening tests as well as gene tests are necessary for correct diagnosis. Increasing the coverage of PFIC3 is meaningful and thus can improve the current understanding of this disease.

Myeloid-Derived Suppressor Cells in Patients With Acute Pancreatitis With Increased Inhibitory Function.

Acute pancreatitis (AP) is pancreatic or systemic inflammation without or with motion organ dysfunction. Severe acute pancreatitis (SAP) is the main cause of death for patients with AP. A pro-/anti-inflammatory imbalance is considered the key regulation of disease severity. However, the real mechanism of SAP remains unclear. This study aimed to identify the frequency and specific roll of myeloid-derived suppressor cell (MDSC) in AP. We evaluated MDSC frequency and disease severity by analyzing MDSCs in the peripheral blood of healthy controls (HCs) and patients with mild acute pancreatitis (MAP) and SAP by flow cytometry. We also compared the frequency and inhibitory ability of MDSCs from HCs and SAP, and finally detected the reason for the difference in inhibitory ability. AP was marked by expansion of MDSCs as well as its subsets, granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (M-MDSCs). The proportion of MDSC in the peripheral blood mononuclear cells of patients with AP was increased and positively correlated with AP severity. The frequency of MDSC was decreased after treatment compared with pre-treatment. CD3+ T cells were remarkably inhibited by MDSC derived from the patients with SAP. In the expression of arginase-1 (Arg-1) and reactive oxygen species (ROS), the MDSCs from patients with SAP increased. These findings demonstrated that MDSCs expanded in the peripheral blood in patients with AP, especially in those with SAP. Moreover, the inhibitory ability of MDSCs was increased in the patients with SAP compared with that in the HCs. The enhanced suppressive function was possibly caused by an overexpression of Arg-1 and ROS.

Effect of cold snare polypectomy for small colorectal polyps.

BACKGROUND: Colorectal cancer remains a considerable challenge in healthcare nowadays. Approximately 60%-80% of colorectal cancer is caused by intestinal polyps, and resection of intestinal polyps has been proved to reduce the incidence of colorectal cancer. The vast majority of intestinal polyps can be found during colonoscopy and removed endoscopically. Therefore, more attention has been paid to the development of endoscopic resection of intestinal polyps. In this study, we compared the efficacy and safety of cold snare polypectomy (CSP) and hot snare polypectomy (HSP). AIM: To investigate the efficacy and safety of CSP and HSP for colorectal polyps. METHODS: Between January and December 2020, 301 patients with colorectal polyps 4-9 mm in diameter were treated with endoscopic therapy in our hospital, and were divided into the CSP group (n = 154) and HSP group (n = 147). The operating time, incidence of bleeding and perforation, use of titanium clips, and complete resection rate were compared between the two groups. RESULTS: We included 249 patients (301 polyps). No differences in gender, age, and polyp size, location, shape and type were observed between the CSP and HSP groups, and the resection rates in these two groups were 93.4% and 94.5%, respectively, with no significant difference. The use of titanium clips was 15.6% and 95.9%, the operating time was 3.2 ± 0.5 min and 5.6 ± 0.8 min, the delayed bleeding rate was 0% and 2.0%, and delayed perforation was 0% and 0.7%, in the CSP and HSP groups, respectively. CONCLUSION: For sessile colorectal polyps < 10 mm, CSP had the same resection rate of impaired tissue integrity as traditional HSP had. The rate of complications was lower in the CSP group. CSP is a safe and effective method for polypectomy.

Lymphoepithelioma­Like Cholangiocarcinoma with Hepatitis C Virus Infection Treated by Microwave Ablation: A Literature Review and Case Report.

Background: Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare type of intrahepatic tumor that is poorly understood. It is not associated with specific physical findings and is usually diagnosed incidentally, resulting in tumors that are often large-sized at diagnosis. At present, the main treatment approach is surgical resection. Case Presentation: Here, we report the case of a patient with LELCC treated with microwave ablation (MWA). Our patient was a Chinese man with chronic hepatitis C and a 51 mm-diameter intrahepatic tumor. Despite blood testing, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging, and abdominal ultrasound, the tumor was not well diagnosed. However, the histopathological findings of ultrasound-guided percutaneous tumor biopsy led to a diagnosis of LELCC. The patient was treated with MWA, and no new lesions had occurred at 9 months after treatment. Conclusion: To our knowledge, this is the first patient with LELCC treated using MWA. Our experience suggests that MWA is an effective new therapeutic method for this disease.

Case Report: Pediatric Hepatic Rhabdomyosarcoma With Maximum Lifetime.

Primary intrahepatic rhabdomyosarcoma is an extremely rare malignant tumor. Here, we describe a case of embryonal rhabdomyosarcoma of the liver in a 7-year-old boy without any symptoms. Serologically, the patient showed abnormal levels of serum tumor markers and liver function. Imaging revealed a large mass in the left lobe of the liver and no lesions elsewhere. At first, the patient was misdiagnosed by percutaneous liver biopsy as having clear cell sarcoma. However, the final diagnosis was established to be hepatic embryonal rhabdomyosarcoma based on postoperative histopathology and typical immunohistochemical staining, which was positive for desmin and myogenin. For treatment, the patient received two cycles of preoperative chemotherapy, prophylactic radiotherapy, and 13 cycles of combined postoperative chemotherapy. Routine follow-ups after all treatment conducted by imaging examinations showed no sign of recurrence or metastasis over 13 months, and the patient survives more than 38 months since initial diagnosis. To our knowledge, this patient is the first with hepatic rhabdomyosarcoma to receive neoadjuvant chemotherapy (preoperative chemotherapy) combined with relative comprehensive treatment and achieve a favorable result.

Dual-Role of Cholesterol-25-Hydroxylase in Regulating Hepatitis B Virus Infection and Replication.

Hepatitis B virus (HBV)-related diseases are among the major diseases that affect millions of people worldwide. These diseases are difficult to eradicate and thus pose a serious global health challenge. There is an urgent need to understand the cross talk mechanism between HBV and the host. Cholesterol-25-hydroxylase (CH25H) and its enzymatic product, 25-hydroxycholesterol (25HC), were previously shown to exhibit effective broad-spectrum antiviral activity. However, the role of CH25H in the regulation of HBV infection and replication remains unclear. The present study reported increased expression of CH25H in HBV-infected patients compared to healthy subjects. Importantly, higher expression of CH25H expression was found to be associated with low HBV replication. Additionally, the present study aimed to identify CH25H mutants, which would lack hydroxylase activity but retain antiviral activity toward HBV infection and replication. Interestingly, it was observed that both CH25H and its mutants interacted with HBx protein and inhibited nuclear translocation of HBx. In particular, CH25H interacted with the C-terminal region of HBx, while transmembrane region 3 of CH25H was found to be critical for CH25H-HBx interaction and inhibition of HBV replication. The study results suggested that 25HC promoted HBV infection but not HBV replication. Thus, the results of the present study suggested the involvement of a dual mechanism in CH25H-mediated regulation of HBV replication. The study clearly demonstrated cross talk between HBV and the host through CH25H-HBx axis. IMPORTANCE The enzymatic product of CH25H, 25-hydroxycholesterol (25HC), has been previously shown to play a critical role in the blockage of the cell-virus fusion in response to viral infection. However, our study indicates a dual role of CH25H in regulating HBV. We find the CH25H-mediated inhibition of HBV replication is independent on its enzyme activity and CH25H binds to HBx and inhibits HBx nucleus translocation. We are interested to find out 25HC promotes HBV infection.

Tenofovir disoproxil fumarate for multiple nucleos(t)ide analogues treatment failure hepatitis B: Is monotherapy enough?

BACKGROUND AND AIM: Tenofovir disoproxil fumarate (TDF) is a first-line treatment for chronic hepatitis B virus (HBV) infection for its high potency and a low rate of drug resistance. This study investigated the efficacy and safety of TDF in Chinese patients with chronic hepatitis B (CHB) infection after treatment failure with multiple nucleos(t)ide analogues (NAs). METHODS: Patients included were aged 18-65 years, with treatment failure with multiple NAs (serum HBV DNA > 200 IU/mL after more than two different NA treatments). The primary endpoint was proportion of patients with serum HBV DNA < 20 IU/mL at Week 144 of TDF monotherapy. Secondary endpoints and safety were also assessed. RESULTS: Overall, 213 patients were enrolled. At Week 144, mean HBV DNA decreased significantly from baseline (4.4 vs 1.4 log10 IU/mL), with 77.0% patients (95% confidence interval: 71.1, 82.9) achieving serum HBV DNA < 20 IU/mL. Three (1.4%) patients experienced virological breakthrough during TDF monotherapy, without hepatitis flare. At Week 144, 15.3% and 4.7% patients (hepatitis B e antigen [HBeAg]-positive at baseline) experienced HBeAg loss and HBeAg seroconversion, respectively; 68.3% patients achieved normalized alanine aminotransferase levels. Overall, 58.7% patients experienced more than one adverse event (AE). Most common AEs were upper respiratory tract infection and blood creatine phosphokinase increase; 8.5% patients experienced study drug-related AEs; 9.4% patients experienced serious AEs (none were TDF-related). Among renal safety parameters, overall trend of mean serum phosphorous level remained stable, while mean estimated glomerular filtration rate increased slightly. CONCLUSIONS: Tenofovir disoproxil fumarate monotherapy is efficacious in CHB patients with multiple NAs treatment failure with no new safety findings.

The Interplay Among HIV, LINE-1, and the Interferon Signaling System.

Human immunodeficiency viruses (HIVs) are retroviruses that replicate effectively in human CD4+ cells and cause the development of acquired immune deficiency syndrome (AIDS). On the other hand, type 1 long interspersed elements (LINE-1s or L1s) are the only active retroelements that can replicate autonomously in human cells. They, along with other active yet nonautonomous retroelements, have been associated with autoimmune diseases. There are many similarities between HIV and LINE-1. Being derived (or evolved) from ancient retroviruses, both HIV and LINE-1 replicate through a process termed reverse transcription, activate endogenous DNA and RNA sensors, trigger innate immune activation to promote interferon (IFN) expression, and are suppressed by protein products of interferon-stimulated genes (ISGs). However, these similarities make it difficult to decipher or even speculate the relationship between HIV and LINE-1, especially regarding the involvement of the IFN signaling system. In this review, we summarize previous findings on the relationships between HIV and innate immune activation as well as between LINE-1 and IFN upregulation. We also attempt to elucidate the interplay among HIV, LINE-1, and the IFN signaling system in hopes of guiding future research directions for viral suppression and immune regulation.

Increased Tim-3+ monocytes/macrophages are associated with disease severity in patients with IgA nephropathy.

T-cell immunoglobulin and mucin-domain-containing protein-3 (Tim-3) plays multiple important roles in immune response and participates in the pathogenesis of various inflammatory diseases by regulating macrophage polarization. However, its functions in the development of IgA nephropathy (IgAN) are still unclear. In this study, changes in the relative levels of Tim-3+ monocytes/macrophages in peripheral blood and renal tissue, and their clinical significance in patients with IgAN were investigated. The expression of CD68 and Tim-3 in macrophages from patients with IgAN was determined via immunohistochemistry and immunofluorescence staining assays. Peripheral blood of 48 patients with biopsy-proven IgAN and 18 healthy controls (HCs) was collected to determine the frequency of circulating CD14+Tim-3+ cells using flow cytometry, before and after 24 weeks of prednisolone treatment. Serum interleukin (IL)-10 and tumor necrosis factor α (TNF-α) levels were measured using enzyme-linked immunosorbent assays. The potential association between clinical signs and Tim-3+ monocytes/macrophages was analyzed. The percentages of circulating CD14+Tim-3+ monocytes were higher in samples from patients with IgAN than in those from HCs and were positively associated with the pathological features (segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis) of IgAN, according to the Oxford classification. Tissue staining assays revealed cells positive for both CD68 and Tim-3 in tubulointerstitial lesions of IgAN patients. In addition, elevated levels of serum IL-10 and TNF-α were detected in these patients in comparison to HCs. Furthermore, the frequency of circulating CD14+Tim-3+ monocytes had a positive correlation with levels of 24-h urinary protein and serum IL-10, and was negatively associated with renal function. After 24 weeks of treatment with prednisolone, the percentages of CD14+Tim-3+ cells were significantly reduced. In summary, our findings indicate that Tim-3+ monocytes/macrophages might be involved in the pathogenesisof IgAN and could be used as a potential indicator to evaluate disease severity.

Neutrophils Modulate Fibrogenesis in Chronic Pulmonary Diseases.

Chronic inflammatory pulmonary diseases are characterized by recurrent and persistent inflammation of the airways, commonly associated with poor clinical outcomes. Although their etiologies vary tremendously, airway neutrophilia is a common feature of these diseases. Neutrophils, as vital regulators linking innate and adaptive immune systems, are a double-edged sword in the immune response of the lung involving mechanisms such as phagocytosis, degranulation, neutrophil extracellular trap formation, exosome secretion, release of cytokines and chemokines, and autophagy. Although neutrophils serve as strong defenders against extracellular pathogens, neutrophils and their components can trigger various cascades leading to inflammation and fibrogenesis. Here, we review current studies to elucidate the versatile roles of neutrophils in chronic pulmonary inflammatory diseases and describe the common pathogenesis of these diseases. This may provide new insights into therapeutic strategies for chronic lung diseases.

Novel Immune Subsets and Related Cytokines: Emerging Players in the Progression of Liver Fibrosis.

Liver fibrosis is a pathological process caused by persistent chronic injury of the liver. Kupffer cells, natural killer (NK) cells, NKT cells, and dendritic cells (DCs), which are in close contact with T and B cells, serve to bridge innate and adaptive immunity in the liver. Meanwhile, an imbalanced inflammatory response constitutes a challenge in liver disease. The dichotomous roles of novel immune cells, including T helper 17 (Th17), regulatory T cells (Tregs), mucosa-associated invariant T cells (MAIT), and innate lymphoid cells (ILCs) in liver fibrosis have gradually been revealed. These cells not only induce damage during liver fibrosis but also promote tissue repair. Hence, immune cells have unique, and often opposing, roles during the various stages of fibrosis. Due to this heterogeneity, the treatment, or reversal of fibrosis through the target of immune cells have attracted much attention. Moreover, activation of hepatic stellate cells (HSCs) constitutes the core of fibrosis. This activation is regulated by various immune mediators, including Th17, Th22, and Th9, MAIT, ILCs, and γδ T cells, as well as their related cytokines. Thus, liver fibrosis results from the complex interaction of these immune mediators, thereby complicating the ability to elucidate the mechanisms of action elicited by each cell type. Future developments in biotechnology will certainly aid in this feat to inform the design of novel therapeutic targets. Therefore, the aim of this review was to summarize the role of specific immune cells in liver fibrosis, as well as biomarkers and treatment methods related to these cells.

Increased red cell distribution width predicts severity of drug-induced liver injury: a retrospective study.

We used a retrospective study design to evaluated the predictive value of red cell distribution width (RDW) for drug-induced liver injury (DILI) severity in Chinese patients with liver biopsy to assist with early DILI management. We included 164 DILI patients with complete laboratory information and medical history. We compared outcomes of 36 patients with severe DILI with outcomes of a control group of 128 patients with mild-to-moderate DILI. Multivariate analyses of risk factors for severe liver injury in Chinese patients with DILI revealed an estimated adjusted odds ratio (AOR) (95% CI) of 4.938 (1.088-22.412) in patients with drinking. Risk for serious liver injury was also increased significantly in patients with dyslipidemia [AOR (95% CI) 3.926 (1.282-12.026)], higher serum total bile acid (TBA) levels [AOR (95% CI) 1.014 (1.009-1.020)] and higher RDW [AOR (95% CI) 1.582 (1.261-1.986)]. The result for area under the curve of 0.905 for TBA levels indicated this variable had high diagnostic performance for predicting DILI severity. Based on an area under the curve value of 0.855, RDW also had superior diagnostic performance in prediction of DILI severity. This performance was not significantly different compared with TBA and was superior compared with other variables, which had area under values ranging from poor to failure (0.527-0.714).The risk for severe DILI was associated with drinking, dyslipidemia, higher TBA levels and RDW values. This study found that RDW and TBA levels were predictors of DILI severity in Chinese patients.

Large leiomyoma of lower esophagus diagnosed by endoscopic ultrasonography-fine needle aspiration: A case report.

BACKGROUND: Benign esophageal tumors are rare accounting for < 1% of esophageal tumors; two-thirds of which are leiomyomas. Esophageal leiomyoma is a benign tumor derived from mesenchymal tissue that is completely muscularly differentiated. Most esophageal leiomyomas are < 5 cm. Esophageal leiomyomas > 5 cm are rare. We describe a case of a large esophageal leiomyoma involving the cardia and diaphragm. CASE SUMMARY: A 35-year-old woman presented to the doctor because of a choking sensation after eating. Physical examination showed no positive signs. Gastroscopy indicated an uplifted change in the cardia. Enhanced computed tomography revealed space-occupying lesions in the lower part of the esophagus and cardia, which were likely to be malignant. Positron emission tomography-computed tomography showed increased metabolism of soft tissue masses in the lower esophagus and near the cardia. Malignant lesions were considered, and mesenchymal tumors were not excluded. Endoscopic ultrasonography was performed to examine a hypoechoic mass in the lower esophagus, which was unclear from the esophageal wall. Clinical evaluation suggested diagnosis of esophageal and cardiac stromal tumors. Finally, histological specimens obtained by endoscopic ultrasonography- fine needle aspiration suggested leiomyoma. The patient underwent laparoscopic local resection of the tumor. The postoperative pathological diagnosis was leiomyoma. CONCLUSION: Endoscopic ultrasonography-fine needle aspiration is necessary for the diagnosis of gastrointestinal leiomyomas. It provides a strong basis for diagnosis of gastrointestinal tumors of unknown nature and origin.