Background. Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a common type of liver failure with a high mortality. This study aimed at investigating the safety and efficacy of the combination treatment of plasma exchange (PE) and umbilical cord-derived mesenchymal stem cell (UC-MSCs) transplantation for HBV-ACLF patients.Methods. A total of 110 HBV-ACLF patients treated in our hospital from January 2012 to September 2017 were enrolled into this trial and divided into the control group (n=30), UC-MSC group (n=30), PE group (n=30), and UC-MSC + PE group (n=20) based on their treatments. The hepatic function, coagulation, and virological and immunological markers were assessed at baseline and 30, 60, 90, 180, and 360 days. The endpoint outcomes were death and unfavorable outcome (need for liver transplantation or death).Results. The UC-MSC + PE group had the lowest rates of death and unfavorable outcome at 30 days, 60 days, and 90 days posttreatment among the four groups, but the difference did not reach significances. The multivariate logistic regression analysis demonstrated that hemoglobin, prothrombin activity, and MELD (model for end-stage liver disease) score were the independent factors associated with the unfavorable outcome (allP<0.05). The levels of total bilirubin, alanine aminotransferase, aspartate transaminase, and MELD score were significantly decreased during treatments (allP<0.05).Conclusion. UC-MSCs combined with PE treatment had good safety but cannot significantly improve the short-term prognosis of HBV-ACLF patients with as compared with the single treatment. The long-term efficacy should be further evaluated. This trial is registered with registration no.NCT01724398.

Calreticulin (CRT) exposure on the cell surface is essential for inducing immunogenic cell death by chemotherapy. Recent studies have shown conflicting effects of chemotherapy-induced autophagy on CRT exposure in cancer cells. Our data revealed that surface-exposed CRT (Ecto-CRT) emission was attenuated by inhibition of autophagy at early stages; however, inhibition of autophagy at late stages resulted in increased Ecto-CRT. Furthermore, neither autophagy activation nor endoplasmic reticulum (ER) stress induction alone was sufficient for CRT surface exposure.Moreover, chemotherapeutic agents that only activated autophagy without inducing ER stress could not increase Ecto-CRT; therefore, combined use of an autophagy activator and ER stress inducer could effectively promote CRT translocation to the plasma membrane. Together, our results highlight the potential of the combined use of ER stress inducers and autophagy late-stage inhibitors to reestablish and strengthen both the CRT exposure and immunogenicity of chemotherapeutic agents induced death cells.

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Objective: As a main cellular component within the disc, nucleus pulposus (NP) cells play important roles in disc physiology. However, little is known on the biologic hallmarks of human NP cells. Therefore, the present study aimed to address the features of human NP cells.Methods: Human NP samples were collected from normal cadavers, patients with scoliosis and disc degeneration as normal, disease control and degenerative NP, respectively. The NP samples were studied using transmission electron microscopy and TUNEL assay. Pre-digested NP samples were studied using flow cytometry with PI/Annexin V staining.Results: Both control and degenerative human NP consisted of mainly viable cells with a variety of morphology. Both necrosis and apoptosis were noted in human NP as forms of cell death with increased apoptosis in degenerative NP, which was further confirmed by the TUNEL assay. Phagocytic NP cells had the hallmarks of both stationary macrophages with lysosomes and NP cells with the endoplasmic reticulum. Annulus fibrosus cells have similar morphologic characteristics with NP cells in terms of cell nest, phagocytosis and intracellular organs. Moreover, NP cells with long processes existed in degenerative and scoliotic NP rather than normal NP. When cultured in glucose-free medium, NP cells developed long and thin processes.Conclusion: Human degenerative NP consists of primarily viable cells. We present direct and in vivo evidence that both human annulus fibrosus and NP cells have phagocytic potential. Moreover, NP cells with long processes exist in both scoliotic and degenerative NP with lack of glucose as one of the possible underlying mechanisms.

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Background: CELSR2 is postulated to be a receptor involved in contact-mediated communication; however, the specific function of this particular member has not been determined in hepatocellular carcinoma (HCC). Methods: Here, we explored the expression and function of CELSR2 in HCC patients through data mining and examined the results using clinical samples and in vitro experiments. Results: It was found that CELSR2 mRNA and protein expression levels were significantly higher in cancerous tissue than in normal tissue. The increased mRNA expression of CELSR2 was significantly associated with overall survival (OS) in HCC patients. Moreover, the genetic alteration rate of CELSR2 gene in HCC can reach 8%, and these alterations would deeply influence its neighboring genes, then jointly affecting the occurrence and development of tumor through cell adhesion and numerous common carcinogenic pathways. Our in vitro results indicated that the depletion of CELSR2 inhibited liver cancer cell proliferation and invasion. Univariate and multivariate Cox regression analyses showed that CELSR2 could be viewed as an independent risk factor for HCC patients.Conclusions: This study demonstrated that data mining could efficiently reveal the roles of CELSR2 in HCC and its potential regulatory networks. The CELSR2 protein level may serve as a novel prognostic biomarker for HCC.

Background Hypertension is a known risk factor for multiple chronic diseases. Existing literature on the association between frequency of spicy food consumption and hypertension shows mixed findings. Methods The analyses are based on the Tongxiang baseline dataset of the China Kadoorie Biobank prospective study, including data from electronic questionnaires, physical measurements and blood sample collection. A total of 53,916 participants aged 30–79 years were included in the final analysis. Multivariable logistic regression was used to estimate the association of spicy food consumption with hypertension, and multiple linear regression was performed to explore the association of spicy food consumption with systolic and diastolic blood pressure. Results Of the 53,916 participants, 23,921 had prevalent hypertension. 12.3% of participants reported consuming spicy food weekly. Among female participants, after adjusting for socio-demographic status, lifestyle factors, BMI, waist circumference, sleep duration and snoring, when compared with females who never consumed spicy food, the odds ratios (95% CI) for hypertension were 1.02 (0.96–1.08), 0.90 (0.79–1.01), and 0.88 (0.78–0.99), respectively, for females who consumed spicy food less than once weekly, 1–2 times weekly, and ≥ 3 times weekly (Ptrend = 0.04). The corresponding odds ratios for males were 1.02 (0.95–1.09), 1.07 (0.95–1.20), and 0.91 (0.81–1.01), respectively (Ptrend = 0.39). Among current alcohol drinkers, compared to participants who never consumed spicy food, the odds ratio (95% CI) for hypertension among participants consuming spicy food daily was 0.98 (0.80–1.20). The corresponding figure for non-current drinkers was 0.72 (0.62–0.84). The association was stronger among non-current alcohol drinkers than among current drinkers (Pheterogeneity = 0.02). Conclusions Frequency of spicy food consumption is inversely associated with hypertension in females, but not in males.

Abstract. The aim of the present study was to investigate the overexpression and significance of ribosomal L1 domain containing 1 (RSL1D1) in prostate cancer (PCA). The present study performed immunohistochemical analysis on the tissues of 138 patients with pathologically confirmed PCA. The patients were followed up for a median of 87 months. In addition, 50 patients with benign prostatic hyperplasia (BPH) were enrolled in the present study as a control group. Of the 138 PCA tissue samples, 124 (89.9%) expressed RSL1D1, while 4 out of the 50 (8.0%) BPH tissues expressed RSL1D1. The present study defined a high RSL1D1 expression level as the relative gene expression that was equal to or higher than the median, and low expression as the gene expression lower than the median. The pathological stage of patients with PCA (≥pT3a vs. pT2c) and the Gleason scores of patients (≥7 vs. <7) were associated with RSL1D1 expression (χ 2 =4.809 and 14.703; P=0.028 and P<0.0001, respectively) and a high expression of RSL1D1 (χ 2 =10.294 and 17.520; P=0.001 and P<0.0001, respectively). Kaplan-Meier curve analysis demonstrated that the biochemical recurrence (BCR)-free survival rate of the patients was increased in patients without RSL1D1 expression (P=0.0046), in those with low RSL1D1 expression (P<0.0001) and in those without RSL1D1 expression in the mesenchyme (P=0.006) compared with those patients with no expression, low expression and no mesenchymal expression, respectively. A high expression level of RSL1D1 was demonstrated to be an independent prognostic factor of BCR in patients with PCA using Cox regression analysis. Overall, the present study demonstrated that RSL1D1 expression was associated with PCA, and that it may aid in the improvement of diagnosis, prognosis and risk stratification of patients with PCA.