Clinical features of patients undergoing hemodialysis with COVID-19.

Hemodialysis patients are susceptible to coronavirus disease 2019 (COVID-19). The aim of this study was to describe the epidemiological, clinical characteristics, and mortality-related risk factors for those who undergoing hemodialysis with COVID-19. We conducted a retrospective study. A total of 49 hemodialysis patients with COVID-19 (Group 1) and 74 uninfected patients (Group 2) were included. For patients in Group 1, we found the median age was 62 years (36-89 years), 59.3% were male, and the median dialysis vintage was 26 months. Twenty-eight patients (57%) had three or more comorbidities and two patients (4%) died. The most common symptoms were fever (32.7%) and dry cough (46.9%), while nine patients (18.4%) were asymptomatic. Blood routine tests indicated lymphocytopenia, the proportion of lymphocyte subsets was generally reduced, and chest CT scans showed ground-glass opacity (45.8%) and patchy shadowing (35.4%). However, these findings were not specific to hemodialysis patients with COVID-19, and similar manifestations could be found in patients without SARS-CoV-2 infection. In conclusion, for hemodialysis patients with COVID-19, lymphocytopenia and ground-glass opacities or patchy opacities were common but not specific to them, early active treatment and interventions against nosocomial infection can significantly reduce the mortality and the risk of SARS-CoV-2 infection.

Identification and Validation of a Novel Clinical Signature to Predict the Prognosis in Confirmed Coronavirus Disease 2019 Patients.

BACKGROUND: Our aim in this study was to identify a prognostic biomarker to predict the disease prognosis and reduce the mortality rate of coronavirus disease 2019 (COVID-19), which has caused a worldwide pandemic. METHODS: COVID-19 patients were randomly divided into training and test groups. Univariate and multivariate Cox regression analyses were performed to identify the disease prognosis signature, which was selected to establish a risk model in the training group. The disease prognosis signature of COVID-19 was validated in the test group. RESULTS: The signature of COVID-19 was combined with the following 5 indicators: neutrophil count, lymphocyte count, procalcitonin, age, and C-reactive protein. The signature stratified patients into high- and low-risk groups with significantly relevant disease prognosis (log-rank test, P < .001) in the training group. The survival analysis indicated that the high-risk group displayed substantially lower survival probability than the low-risk group (log-rank test, P < .001). The area under the receiver operating characteristic (ROC) curve showed that the signature of COVID-19 displayed the highest predictive accuracy regarding disease prognosis, which was 0.955 in the training group and 0.945 in the test group. The ROC analysis of both groups demonstrated that the predictive ability of the signature surpassed the use of each of the 5 indicators alone. CONCLUSIONS: The signature of COVID-19 presents a novel predictor and prognostic biomarker for closely monitoring patients and providing timely treatment for those who are severely or critically ill.

Lipoxin A4 suppresses angiotensin II type 1 receptor autoantibody in preeclampsia via modulating caspase-1.

Preeclampsia (PE) remains a leading cause of maternal and neonatal morbidity and mortality. Numerous studies have shown that women with PE develop autoantibody, termed angiotensin II type 1 receptor autoantibody (AT1-AA), and key features of the disease result from it. Emerging evidence has indicated that inflammatory cell necrosis, such as pyroptosis, could lead to autoantigen exposure and stimulate autoantibody production. Caspase-1, the central enzyme of inflammasome and key target of pyroptosis, may play roles in AT1R exposure and AT1-AA production. Exploring endogenous regulator that could inhibit AT1-AA production by targeting pyroptosis will be essential for treating PE. Lipoxin A4 (LXA4), endogenous dual anti-inflammatory and proresolving lipid mediator, may inhibit AT1-AA production via modulating caspase-1. Thus, we explore whether caspase-1 is essential for AT1-AA production and LXA4 inhibits AT1-AA via modulating caspase-1. PE patients and mice developed AT1-AA associated with caspase-1 activation. Caspase-1 deletion leaded to AT1-AA decrease in PE mice. Consistent with these findings, we confirmed caspase-1 activation, trophoblast pyroptosis and AT1R exposure in PE mice and trophoblast model, while caspase-1 deficiency showed decreased trophoblast pyroptosis and AT1R exposure in vitro and in vivo. Interestingly, LXA4 could suppress AT1-AA production via regulating caspase-1 as well as enhancing phagocytosis of dead trophoblasts by macrophages. These results suggest that caspase-1 promotes AT1-AA production via inducing trophoblast pyroptosis and AT1R exposure, while LXA4 suppresses AT1-AA production via modulating caspase-1, supporting caspase-1 serving as a therapeutic target for attenuating AT1-AA and LXA4 protecting patients from AT1-AA and PE.

Long noncoding RNA ROR promotes breast cancer by regulating the TGF-ß pathway.

BACKGROUND: Breast cancer is the leading cause of oncological mortality among women. Efficient detection of cancer cells in an early stage and potent therapeutic agents targeting metastatic tumors are highly needed to improve survival rates. Emerging evidence indicates that lncRNAs (long noncoding RNAs) are critical regulators of fundamental cellular processes in a variety of tumors including breast cancer. The functional details of these regulatory elements, however, remain largely unexplored. METHODS: In this study, lncRNA ROR (linc-ROR) was examined by real-time PCR in different breast cancer cell lines and breast tumor tissues/non-tumor tissues were collected from both breast cancer patients and healthy controls. Linc-ROR was knockdown in breast cancer cell lines and the effects on cell proliferation, migration and invasion were tested both in vitro and in vivo tumor model. Effects of linc-ROR knockdown on TGF-ß signaling pathway were investigated by Western blot. RESULTS: Our studies have suggested that linc-ROR, a critical factor for embryonic stem cell maintenance, probably acts as an oncogenic factor in breast cancer cells, causing poor prognostic outcomes. Overexpression of linc-ROR seems to be responsible for promoting proliferation and invasion of cancer cells as well as tumor growth in nude mice. The regulatory action of linc-ROR can affect the activity of the TGF-ß signaling pathway, which has been proven critical for mammary development and breast cancer. CONCLUSIONS: The results have highlighted the potential importance of linc-ROR in the progression of advanced breast cancer, and thus will stimulate efforts in the development of novel diagnostic and therapeutic strategies.

[Impact of JNK inhibitor XG-102 in a diet-induced rat model of non-alcoholic steatohepatitis].

OBJECTIVE: To observe the impact of the JNK inhibitor XG-102 in a diet-induced rat model of non-alcoholic steatohepatitis. METHODS: Forty-eight Sprague-Dawley male rats were subjected to a percutaneous superior mesenteric vein retention catheter operation and fed with a standard diet for 10 days, after which the rats were randomly divided into the following three groups: normal control (NC) group; high-fat (HF) model group; XG-102 treatment group. The HF group was fed an HF diet and treated with 0.9% sodium chloride for 16 weeks. The XG-102 group was fed an HF diet for 16 weeks and simultaneously treated with XG-102 (1 mg/kg) once per day for 4 weeks. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), homeostasis model of assessment insulin resistance (HOMA-IR) and tumor necrosis factor-alpha (TNFa) were measured. Liver histological changes were observed. The protein expressions of phospho-c-Jun and cleaved caspase-3 were detected by western blotting. RESULTS: Compared with the NC group, the HF group showed significantly higher levels of serum ALT, AST, TC, TG, HOMA-IR and TNFa (P<0.05). Compared with the HF group, the XG-102 group showed significantly lower levels of serum ALT, AST, TC, TG, HOMA-IR and TNFa (P<0.05). The HF group also showed significantly higher protein expression of phospho-c-Jun and cleaved caspase-3 than the NC group (P<0.05) and the XG-102 group (P<0.05). CONCLUSION: The JNK inhibitor XG-102 may ameliorate lipid metabolism, reduce insulin resistance, decrease liver injury and inhibit hepatocytes apoptosis.