Bangmao Wang

Enteropathy-associated T-cell lymphoma presenting with gastrointestinal tract symptoms: A report of two cases and review of diagnostic challenges and clinicopathological correlation.

The gastrointestinal tract is the most common location for primary extranodal non-Hodgkin lymphoma (NHL) with cases less commonly found in the intestine. The majority of primary intestinal B-cell lymphomas are exophytic, whereas enteropathy-associated T-cell lymphomas present predominantly as thickened plaques, ulcers or strictures. Crohn’s disease (CD) is a chronic inflammatory disease of the intestines with fissures and ulcers, which is difficult for clinicians to diagnose based on endoscopic observations alone. Malignant lymphoma must be considered when clinically diagnosed CD is refractory to medication or when its clinical course becomes aggressive. The current study presents a rare case of primary colon T-cell lymphoma in a 16-year-old male with poor prognosis, as well as a case of gastrointestinal lymphoma occurring in the duodenum and colon in a 62-year-old male with a 10-year history of NHL. It was difficult to determine the diagnosis by a single endoscopic biopsy as the majority of biopsy specimens revealed mixed inflammation within which the lymphoma cells were difficult to identify. The present study indicated that it is important to recognize ulcerative or stenotic lymphoma and to differentiate it from CD as it exhibits a much more aggressive clinical behavior. The correct diagnosis may be confirmed by careful histopathological study and ancillary examination.

Prognostic nomogram incorporating neutrophil-to-lymphocyte ratio for early mortality in decompensated liver cirrhosis

Background: Neutrophil‐to‐lymphocyte ratio (NLR) is a marker of systemic inflammation. However, its predictive utility of 30‐day mortality remains elusive in decompensated cirrhotics. Aims: We aimed to combine NLR and other variables associated with early mortality of cirrhotics with acute insults in to a predictive nomogram. Methods: We retrospectively analyzed 352 decompensated cirrhotics. The 30‐day mortality was regarded as primary outcome. Multivariate Cox analysis was performed, and a NLR‐based nomogram was developed. The performance of nomogram was determined in terms of its calibration, discrimination and clinical usefulness. Serum cytokines were evaluated by Milliplex cytokine assay. Results: On multiple analysis, independent factors for early mortality were albumin, MELD and NLR, which were all selected into the nomogram. The nomogram showed good discrimination, with a concordance index of 0.88. Calibration of the nomogram predicted survival corresponding optimally with the actual outcomes. Decision curve analysis indicated our nomogram was useful in clinical practice. Among circulating cytokines we investigated, IL‐6 and IL‐8 were substantially elevated in cirrhotics compared to healthy subjects. High NLR was positively correlated with the expression of IL‐6 and IL‐8. Conclusion: The proposed nomogram incorporating NLR offered an individualized predictive tool for 30‐day mortality in decompensated cirrhotics. The escalating value of NLR likely implicated excessive inflammatory response.

The Effects of Berberine on Concanavalin A-Induced Autoimmune Hepatitis (AIH) in Mice and the Adenosine 5’-Monophosphate (AMP)-Activated Protein Kinase (AMPK) Pathway

Background Berberine, a herbal extract, has been reported to protect against inflammatory disorders. The adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway can be activated by berberine and inhibited by the synthetic, reversible AMP-competitive inhibitor, Compound C. The aim of this study was to investigate the effects of berberine on concanavalin A (Con A)-induced autoimmune hepatitis (AIH) in mice via the AMPK pathway. Material/Methods BALB/c mice were treated with berberine, with or without Compound C, followed by treatment with Con A. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Liver tissue histology was performed to evaluate hepatic injury and AIH. Cytokine levels in serum and hepatic tissue were measured by enzyme-linked immunoassay (ELISA) and used quantitative polymerase chain reaction (qPCR). Levels of phosphorylated acetyl coenzyme-A carboxylase (ACC), representing AMPK activation, were detected by Western blotting. Results Serum ALT and AST levels were significantly reduced by berberine (100 and 200 mg/kg/day) in mice with Con A-induced hepatitis. Berberine also reduced Con A-induced hepatocyte swelling, cell death, and infiltration of leukocytes. Serum levels of tumor necrosis factor (TNF)-alpha, interferon (IF)-gamma, interleukin (IL)-2, and IL-1beta were reduced by berberine pre-treatment; levels of serum IL-10, an anti-inflammatory cytokine, was elevated. These protective effects of berberine on Con-A-induced AIH were reversed by treatment with Compound C. Conclusions In a murine model of Con A-induced AIH, berberine treatment reduced hepatic injury via activation of the AMPK pathway. Further studies are recommended to determine the potential therapeutic role for berberine in AIH.

The importance of IgG4 screening in patients diagnosed with primary sclerosing cholangitis in the past: A case rediagnosed as IgG4-SC after 10 years.

Rationale:While primary sclerosing cholangitis (PSC) has been recognized for decades, immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) has been correctly diagnosed only in recent years. PSC and IgG4-SC show similar clinical symptoms, serologic markers, and imaging results, but the treatment strategies and prognosis of patients differ. Patient concerns:Here, we present the case report of a patient diagnosed with PSC for 10 years and rediagnosed with IgG4-SC recently, to emphasize the importance of screening serum IgG4 levels in patients with previous diagnosis of PSC. Diagnoses:A 57-year-old woman with 10-year history of PSC was hospitalized due to pruritus. In 2004, the patient underwent cholecystectomy and cholangioenterostomy because of unexplained jaundice with pancreatic swelling. In the last 10 years, her liver enzyme levels were continuously elevated. The latest liver function profile showed elevated alanine aminotransferase, aspartate aminotransferase, and total bilirubin. IgG4 was 3.69 (0.03–2.01 g/L). Immunohistochemical staining of the surgical specimen showed >10 IgG4-positive plasma cells per high-power field, and IgG4+/IgG+ plasma cells >40%. Interventions and outcomes:She was treated with prednisone 40 mg once-daily and the dose was gradually tapered. The patient remains well after 18 months. Lessons subsections:Patients with IgG4-SC may be misdiagnosed as PSC due to lack of IgG4 screening. It is important to perform IgG4 screening in patients diagnosed as PSC. Steroid is effective to prevent disease progression in these patients.

Receptor-interacting protein kinase 3 mediates macrophage/monocyte activation in autoimmune hepatitis and regulates interleukin-6 production:

Background The mechanisms of macrophages/monocytes in autoimmune hepatitis (AIH) remain unclear. We investigated the role of receptor-interacting protein kinase 3 (RIP3), a key inflammatory signal adapter, in macrophage/monocyte activation in AIH. Methods Liver tissues and monocytes from patients were collected to evaluate the relationship between macrophage activation and RIP3 by double-immunofluorescence and Western blotting. RAW264.7 macrophages were used to study the regulation of RIP3 signaling on inflammatory cytokines. Results Compared to the hepatic cyst, the majority of accumulated macrophages expressed RIP3 in AIH liver tissues. Moreover, RIP3 expression of monocytes was correlated with the levels of serum hepatic enzyme in AIH. Furthermore, RIP3 signaling was activated by lipopolysaccharide in RAW264.7 macrophages, which was accompanied with upregulated interleukin (IL)-1β, IL-6, and IL-10 and downregulated IL-4 and transforming growth factor-β. Notably, necrostatin-1, the specific inhibitor of the RIP3 signaling pathway, and 6-thioguanine (6-TG), the active metabolite of azathioprine, predominantly reduced IL-6 production compared to other cytokines. Moreover, the gene level of IL-6 was dramatically increased in AIH liver tissues. Conclusions RIP3 signaling is involved in macrophage/monocyte activation in AIH and mediates IL-6 production, and is a novel molecular mechanism of 6-TG, indicating that it might be a promising therapeutic target for AIH treatment.

Sex differences in risk factors of uncomplicated colonic diverticulosis in a metropolitan area from Northern China

As the world’s most populated and rapidly aging country, there is limited information on sex-related differences in factors regarding uncomplicated colonic diverticulosis in China. We aimed to investigate sex differences in individual risk factor in a northern metropolis. Patients with colonic diverticulosis who underwent indicated colonoscopy were queried with respect to medical history and demographic features. Demographic information, life style factors and co-morbidities were retrieved from a prospective dataset. Multiple regression analyses were performed to determine precipitating factors of diverticula. Of 4,386 enrolled patients, colonic diverticulosis were detected in 218 cases (4.97%). Multiple logistic regression analysis implicated increasing age (OR = 1.05, 95%CI 1.03–1.06, P < 0.001), red meat ≥100 g/d (OR = 2.53, 95%CI 1.72–3.70, P < 0.001), smoking (OR = 2.14, 95%CI 1.05–4.33, P = 0.035), rheumatologic diseases (OR = 3.38, 95%CI 1.09–10.5, P = 0.035) and NSAIDs (OR = 2.11, 95%CI 1.12–3.97, P = 0.020) were significantly associated with diverticulosis in men, whilst advancing age (OR = 1.03, 95%CI 1.01–1.05, P = 0.013), BMI (OR = 1.12, 95%CI 1.04–1.19, P = 0.001), smoking (OR = 10.2, 95%CI 2.81–37.4, P < 0.001), rheumatologic diseases (OR = 8.04, 95%CI 3.05–21.2, P < 0.001), hypertension (OR = 1.76, 95%CI 1.01–3.06, P = 0.047), colonic polyps (OR = 3.12, 95%CI 1.82–5.36, P < 0.001) and antihypertensive medications (OR = 2.99, 95%CI 1.66–5.39, P < 0.001) in women. In conclusion, it is pivotal to take account of differentially sex-related factors in regard to the development of uncomplicated colonic diverticulosis.

miR-181a regulates Th17 cells distribution via up-regulated BCL-2 in primary biliary cholangitis

Background Primary biliary cholangitis (PBC) is an autoimmune liver disease characterised by destruction of small intrahepatic bile ducts. Recent studies suggest that miRNAs play a critical role in the pathogenesis of liver diseases. However the role served by miRNAs in the pathogenesis of PBC is still not clear. Methods The differentially expressed genes and miRNAs were identified by bioinformatics analysis. Gene ontology and KEGG pathway analyses were conducted to explore the function of the differentially expressed genes. miRNA target genes were predicted using miRecords. The differentially expressed genes and miRNAs were validated by qRT‐PCR in PBC patients along with healthy controls and chronic hepatitis B patients as control. Flow cytometric analysis was conducted to identify the Th17 and Treg cells frequency. Results 15 differentially expressed miRNAs and 1897 mRNAs were identified from the profile. miR‐181a was validated as the differentially expressed miRNA. BCL‐2 and CDKN1B were predicted as the target gene of miR‐181a and validated differentially expressed in PBC patients. However, only BCL‐2 was negative correlated with miR‐181a. The Th17 cells frequency was increased in PBC patients while the Treg cells frequency was decreased. Moreover, the expression of BCL‐2 was positive correlated with Th17 cells frequency. Conclusion Down‐regulated miR‐181a in CD4+ T cells may decrease apoptosis of Th17 cells via up‐regulated BCL‐2 in the pathogenesis of PBC. HighlightsThe expression of miR‐181a was down‐regulated in PBC patients.BCL‐2 was up‐regulated in PBC patients and negatively correlated with miR‐181a.Th17 cells frequency was increased in PBC patients and positively correlated with BCL‐2.

External validation and improvement of LiFe score as a prediction tool in critically ill cirrhosis patients: External validation of the LiFe score

The LiFe (liver, injury, failure, evaluation) score, calculated according to arterial lactate, total bilirubin, and international normalized ratio (INR), is a novel score for risk prediction in intensive care unit (ICU) patients with cirrhosis. The present study aimed to externally validate and optimize the LiFe score for predicting outcomes in critically ill cirrhosis patients.