Peripheral infusion of allogeneic bone marrow-derived MSCs is safe and convenient for patients with HBV-related ACLF and significantly increases the 24-week survival rate by improving liver function and decreasing the incidence of severe infections. (Hepatology 2017;66:209-219).

Ethnicity and environmental factors could be involved in the heterogeneity of systemic lupus erythematosus (SLE). We conducted this study to define clinical and serologic correlations and autoantibody clusters in SLE patients in South China. We retrospectively reviewed the records of 917 patients with SLE admitted to our hospital between January 2005 and June 2008. We found the following associations between autoantibodies and clinical manifestations to be statistically significant: anti-double-stranded DNA (anti-dsDNA) with higher prevalence of renal disorder, leukopenia, and anemia; anti-Sm with higher prevalence of malar rash/discoid rash, pericarditis, and leukopenia; anti-ribonucleoprotein (anti-RNP) with higher prevalence of Raynaud phenomenon and photosensitivity; anti-deoxyribonucleoprotein (anti-DNP) with higher prevalence of arthritis and lower prevalence of renal disorder; anti-Scl-70 with higher prevalence of anemia and Raynaud phenomenon; anti-Jo-1 with higher prevalence of pericarditis; and anti-centromere with higher prevalence of Raynaud phenomenon. Three autoantibody clusters were identified: Cluster 1 (anti-Ro, anti-Sm, and anti-RNP [Ro/Sm/RNP], with a significantly lower percentage of elderly SLE and higher prevalence of photosensitivity, malar rash/discoid rash, Raynaud phenomenon, and leukopenia); Cluster 2 (anti-Ro [Ro], with a lower percentage of pediatric SLE); and Cluster 3 (the absence of anti-extractable nuclear antigen antibodies [ENA ve], with a lower percentage of adult SLE and lower prevalence of alopecia). In summary, this study not only confirms both anti-dsDNA and anti-Sm as specific markers for classifying SLE, but also demonstrates that photosensitivity is not associated with anti-Ro but with anti-RNP, and a negative association is found between renal disorder and anti-DNP in patients in South China. These results are different from results found in other populations. The higher prevalence of anti-dsDNA and renal disorder results in less difference in the prevalence of anti-dsDNA and renal disorder among the 3 autoantibody clusters in SLE patients in South China, which could be related to ethnicity and widespread industrial pollution in South China.

Dexamethasone cannot improve liver functions and 12-week survival rates of patients with HBV-related ACLF. Age, MELD score, and encephalopathy are independent risk factors.

Background: Conventional prognostic models do not fully reflect the severity of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). This study aimed to establish an effective and convenient nomogram for patients with HBV-related ACLF.Methods: A nomogram was developed based on a retrospective cohort of 1,353 patients treated at the Third Affiliated Hospital of Sun Yat-sen University from January 2010 to June 2016. The predictive accuracy and discriminatory ability of the nomogram were determined by a concordance index (C-index) and calibration curve, and were compared with current scoring systems. The results were validated using an independent retrospective cohort of 669 patients consecutively treated at the same institution from July 2016 to March 2018. This study is registered at ClinicalTrials.gov (NCT03992898).Results: Multivariable analysis of the derivation cohort found that independent predictors of 90-day survival were age, white blood cell (WBC) count, hemoglobin (Hb), aspartate aminotransferase (AST), total bilirubin (TBil), international normalized ratio, serum creatinine (Cr), alpha fetoprotein (AFP), serum sodium (Na), hepatic encephalopathy (HE), pre-existing chronic liver disease(PreLD), and HBV DNA load. All factors were included in the nomogram. The nomogram calibration curve for the probability of 90-day survival indicated that nomogram-based predictions were in good agreement with actual observations. The C-index of the nomogram was 0.790, which was statistically significantly greater than those for the current scoring systems in the derivation cohort (P < 0.001). The results were confirmed in the validation cohort.Conclusions: The proposed nomogram is more accurate in predicting the 90-day survival of patients with HBV-related ACLF than current commonly used methods.

Fibroblast-like synoviocytes (FLSs) are the predominant effector cells in the pathological progression of rheumatoid arthritis (RA). Therefore, elucidating the underlying molecular mechanism of the biologic behaviors in RA-FLSs will be helpful in developing the potent targets for the treatment of RA. We have previously documented that the tumor-like biologic behaviors of RA-FLSs are exacerbated by urokinase-type plasminogen activator receptor (uPAR), a specifically up-regulated receptor in RA-FLSs.Here, we investigate the further mechanism of uPAR and clarify its function in RA-FLSs. We demonstrate that miR-221-3p positively correlates to uPAR and regulates uPAR level in RA-FLSs. Simultaneously, one long noncoding RNA, nuclear paraspeckle assembly transcript 1_1 (NEAT1_1) is identified, which can predictively target miR-221-3p at three sites, indicating a strong possibility of being a competing endogenous RNA in RA-FLSs. Interestingly, NEAT1_1 and miR-221-3p can colocate in the nucleus and cytoplasm in RA-FLSs. Importantly, NEAT1_1 can act as a rheostat for the miR-221-3p/uPAR axis and the downstream JAK signaling. In line with the biologic function, NEAT1_1 negatively regulates the tumor-like characters, and cytokine secretions of RA-FLSs. Collectively, our data provide new insight into the mechanisms of NEAT1_1 in modulating RA-FLSs tumor-like behaviors. The targeting of NEAT1_1 and miR-221-3p/uPAR axis may have a promising therapeutic role in patients with RA.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory in joints. Invasive pannus is a characteristic pathological feature of RA. RA fibroblast-like synoviocytes (FLSs) are showed tumor-like biological characters that facilitate pannus generation. Importantly, it has been documented that extracellular vesicle (EVs) derived microRNAs have a vital role of angiogenesis in various immune inflammatory diseases. However, whether RA FLSs derived EVs can facilitate angiogenesis and the underlying mechanism is undefined. Herein, we aim to investigate the key role of RA FLSs derived EVs on angiogenesis in endothelial cells (ECs). We indicate that RA FLSs derived EVs promote ECs angiogenesis by enhancing migration and tube formation of ECs in vitro. Also, we confirm that RA FLSs derived EVs can significantly facilitate ECs angiogenesis with a matrigel angiogenesis mice model. In terms of the mechanisms, both RNAs and proteins in EVs play roles in promoting ECs angiogenesis, but the RNA parts are more fundamental in this process. By combining microRNA sequencing and qPCR results, miR-1972 is identified to facilitate ECs angiogenesis. The blockage of miR-1972 significantly abrogated the angiogenesis stimulative ability of RA FLSs derived EVs in ECs, while the overexpression of miR-1972 reversed the effect in ECs. Specifically, the p53 level is decreased, and the phosphorylated mTOR is upregulated in miR-1972 overexpressed ECs, indicating that miR-1972 expedites angiogenesis through p53/mTOR pathway. Collectively, RA FLSs derived EVs can promote ECs angiogenesis via miR-1972 targeted p53/mTOR signaling, targeting on RA FLSs derived EVs or miR-1972 provides a promising strategy for the treatment of patients with RA.

Background: Ventriculoperitoneal (VP) shunting in cryptococcal meningitis (CM) patients with high intracranial pressure (ICP) has been studied extensively. Methods: A total of 74 CM patients with ICP were identified, including 27 patients with or without ventriculomegaly receiving VP shunting. Results: Through retrospective analysis, there was an obvious decline in ICP as well as Cryptococcus count after VP shunting. Damage to the cranial nerves was improved after the surgery. For those patients receiving VP shunting, there was an obvious decline in ICP as well as Cryptococcus count, with less usage of mannitol. Hydrocephalus or ventriculomegaly was improved, and both the clearance time of Cryptococcus and the hospitalization time were shortened (p < 0.05). The complications of VP shunting were not common. Conclusions: For patients diagnosed with CM and with apparent ICP, VP shunting can be considered regardless of whether there is damage to the cranial nerves or hydrocephaly.

Macrophages are an important component of the human immune system and play a key role in the immune response, which can protect the body against infection and regulate the development of tissue inflammation. Some studies found that macrophages can produce extracellular traps (ETs) under various conditions of stimulation. ETs are web-like structures that consist of proteins and DNA. ETs are thought to immobilize and kill microorganisms, as well as play an important role in tissue damage, inflammatory progression, and autoimmune diseases. In this review, the structure, identification, mechanism, and research progress of macrophage extracellular traps (METs) in related diseases are reviewed.