This Guangzhou retrospective study revealed that proper use of corticosteroid in confirmed critical SARS resulted in lowered mortality and shorter hospitalization stay, and was not associated with significant secondary lower respiratory infection and other complications.

Tiotropium resulted in a higher FEV than placebo at 24 months and ameliorated the annual decline in the FEV after bronchodilator use in patients with COPD of GOLD stage 1 or 2. (Funded by Boehringer Ingelheim and others; Tie-COPD ClinicalTrials.gov number, NCT01455129 .).

BackgroundNicotinamide riboside (NR) is a nicotinamide adenine dinucleotide (NAD+) precursor which is present in foods such as milk and beer. It was reported that NR can prevent obesity, increase longevity, and promote liver regeneration. However, whether NR can prevent ethanol-induced liver injuries is not known. This study aimed to explore the effect of NR on ethanol induced liver injuries and the underlying mechanisms.MethodsWe fed C57BL/6 J mice with Lieber-DeCarli ethanol liquid diet with or without 400 mg/kg·bw NR for 16 days. Liver injuries and SirT1-PGC-1α-mitochondrial function were analyzed. In in vitro experiments, HepG2 cells (CYP2E1 over-expressing cells) were incubated with ethanol ± 0.5 mmol/L NR. Lipid accumulation and mitochondrial function were compared. SirT1 knockdown in HepG2 cells were further applied to confirm the role of SirT1 in the protection of NR on lipid accumulation.ResultsWe found that ethanol significantly decreased the expression and activity of hepatic SirT1 and induced abnormal expression of enzymes of lipid metabolism in mice. Both in vivo and in vitro experiments showed that NR activated SirT1 through increasing NAD+ levels, decreased oxidative stress, increased deacetylation of PGC-1α and mitochondrial function. In SirT1 knockdown HepG2 cells, NR lost its ability in enhancing mitochondrial function, and its protection against lipid accumulation induced by ethanol.ConclusionsNR can protect against ethanol induced liver injuries via replenishing NAD+, reducing oxidative stress, and activating SirT1-PGC-1α-mitochondrial biosynthesis. Our data indicate that SirT1 plays an important role in the protection of NR against lipid accumulation and mitochondrial dysfunctions induced by ethanol.

MRI can clearly demonstrate shape, margin, internal components and surrounding tissues. Different subtypes of retroperitoneal liposarcoma exhibited varying MRI features, depending on tumor histological components. MRI should be an ideal method for diagnosing retroperitoneal liposarcoma.

Although chimeric antigen receptor (CAR)-engineered T cells have shown great success in the treatment of B cell malignancies, this strategy has limited efficacy in patients with solid tumors. In mouse CAR-T cells, IL-7 and CCL19 expression have been demonstrated to improve T cell infiltration and CAR-T cell survival in mouse tumors. Therefore, in the current study, we engineered human CAR-T cells to secrete human IL-7 and CCL19 (7 × 19) and found that these 7 × 19 CAR-T cells showed enhanced capacities of expansion and migration in vitro. Furthermore, 7 × 19 CAR-T cells showed superior tumor suppression ability compared to conventional CAR-T cells in xenografts of hepatocellular carcinoma (HCC) cell lines, primary HCC tissue samples and pancreatic carcinoma (PC) cell lines. We then initiated a phase 1 clinical trial in advanced HCC/PC/ovarian carcinoma (OC) patients with glypican-3 (GPC3) or mesothelin (MSLN) expression. In a patient with advanced HCC, anti-GPC3-7 × 19 CAR-T treatment resulted in complete tumor disappearance 30 days post intratumor injection. In a patient with advanced PC, anti-MSLN-7 × 19 CAR-T treatment resulted in almost complete tumor disappearance 240 days post-intravenous infusion. Our results demonstrated that the incorporation of 7 × 19 into CAR-T cells significantly enhanced the antitumor activity against human solid tumor. Trial registration: NCT03198546. Registered 26 June 2017, https://clinicaltrials.gov/ct2/show/NCT03198546?term=NCT03198546&draw=2&rank=1

The aim of the present study was to determine the role of hydrogen sulfide (H2S) in improving myocardial fibrosis and its effects on oxidative stress, endoplasmic reticulum (ER) stress and cell apoptosis in diabetic rats, by regulating the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. A total of 40 male Sprague-Dawley rats were randomly divided into four groups (n=10) as follows: Normal (control group), diabetes mellitus [streptozotocin (STZ) group], diabetes mellitus treated with H2S (STZ + H2S group), and normal rats treated with H2S (H2S group). Diabetes in rats was induced by intra-peritoneal (i.p.) injection of STZ at a dose of 40 mg/kg. NaHS (100 µmol/kg, i.p.), which was used as an exogenous donor of H2S, was administered to rats in the STZ + H2S and H2S groups. After 8 weeks, the pathological morphological changes in myocardial fibers were observed following hematoxylin and eosin and Masson's trichrome staining. Apoptosis of myocardial tissue was analyzed by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Oxidative stress was evaluated through detecting the content of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), glutathione (GSH) and superoxide dismutase (SOD) in the myocardial cells by ELISA. The expression of collagen III, matrix metalloproteinase (MMP)8, MMP14, tissue inhibitor of metalloproteinase (TIMP)2, transforming growth factor (TGF)-β, cystathionine-γ-lyase (CSE), eukaryotic initiation factor 2α (eIF2α), GRP94, Bcl-2, caspase-3, tumor necrosis factor (TNF)-α, nuclear factor-κB (NF-κB) and proteins related to the JAK/STAT pathway, was detected by western blot analysis. The results indicated that the array of myocardial cells was markedly disordered in STZ group rats; compared with the control group, both myocardial interstitial fibrosis and the deposition of collagen III were increased. Furthermore, the expression ratio of MMPs/TIMPs was dysregulated, while the expression levels of TGF-β, eIF2α, GRP94, caspase-3, TNF-α, NF-κB, MDA and 4-HNE were significantly increased. Furthermore, the expressions of JAK-1/2 and STAT1/3/5/6 were also markedly upregulated, while those of CSE, SOD, GSH and Bcl-2 were downregulated. Compared with the STZ group, these changes were reversed in the STZ + H2S group. The results of the present study demonstrated that H2S can improve myocardial fibrosis in diabetic rats, and the underlying mechanism may be associated with the downregulation of the JAK/STAT signaling pathway, thereby suppressing oxidative stress and ER stress, inflammatory reaction and cell apoptosis.

Nowadays, there has been an increase in the number of people with chronic wounds, which has resulted in serious health problems worldwide. The rate-limiting stage of chronic wound healing has...

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