Background The outbreak of the coronavirus disease 2019 (Covid‐19) has shown a global spreading trend. Early and effective predictors of clinical outcomes are urgently needed to improve management of Covid‐19 patients. Objective The aim of the present study was to evaluate whether elevated D‐dimer levels could predict mortality in patients with Covid‐19. Methods Patients with laboratory confirmed Covid‐19 were retrospective enrolled in Wuhan Asia General Hospital from January 12, 2020, to March 15, 2020. D‐dimer levels on admission and death events were collected to calculate the optimum cutoff using receiver operating characteristic curves. According to the cutoff, the subjects were divided into two groups. Then the in‐hospital mortality between two groups were compared to assess the predictive value of D‐dimer level. Results A total of 343 eligible patients were enrolled in the study. The optimum cutoff value of D‐dimer to predict in‐hospital mortality was 2.0 µg/mL with a sensitivity of 92.3% and a specificity of 83.3%. There were 67 patients with D‐dimer ≥2.0 µg/mL, and 267 patients with D‐dimer <2.0 µg/mL on admission. 13 deaths occurred during hospitalization. Patients with D‐dimer levels ≥2.0 µg/mL had a higher incidence of mortality when comparing with those who with D‐dimer levels <2.0 µg/mL (12/67 vs 1/267, P < .001; hazard ratio, 51.5; 95% confidence interval, 12.9‐206.7). Conclusions D‐dimer on admission greater than 2.0 µg/mL (fourfold increase) could effectively predict in‐hospital mortality in patients with Covid‐19, which indicated D‐dimer could be an early and helpful marker to improve management of Covid‐19 patients. (Chinese Clinical Trial Registry: ChiCTR2000031428).

Recently, it was shown that hepatocyte DNA synthesis after partial hepatectomy (PH) is impaired in interleukin-6-deficient (IL-6 ؊/؊ ) mice, which results in significantly delayed, but eventual, recovery of normal liver weight, compared with the IL-6 ؉/؉ controls. Four possible compensatory mechanisms might explain this phenomenon: 1) hepatocyte hypertrophy; 2) activation of the oval cell compartment and subsequent maturation to hepatocytes; 3) non-oval biliary epithelial cell (BEC) proliferation; and/or 4) differential rates of apoptotic cell death in the regenerating liver. These hypotheses were tested by subjecting IL-6 ؊/؊ and IL-6 ؉/؉ mice to PH and determining sequential liver weight, histology, hepatocyte and BEC 5Ј-bromo-2Ј-deoxyuridine (BrdU) labeling, liver DNA content, ␣-fetoprotein (AFP) mRNA production, and apoptosis at several time points after PH. Consistent with previous studies, we show that the absence of IL-6 significantly impairs hepatocyte DNA synthesis and delays liver weight recovery after PH, but the defect observed in this study is less severe than that previously reported, and no excess mortality, massive necrosis on histology, nor differences in liver injury test are seen. Interestingly, the IL-6 ؊/؊ mice show more hepatocyte BrdU pulse labeling than the IL-6 ؉/؉ controls at 24 hours, but less at 36, 48, and 60 hours. Continuous BrdU infusion up to 60 hours after PH showed a cumulative hepatocyte labeling index of 79.5% in IL-6 ؉/؉ mice and 70.8% in IL-6 ؊/؊ mice, respectively (P F .03). However, despite a lower labeling index and significantly delayed weight recovery, hepatic mass was equally restored in the two groups by 96 hours. There was no evidence of oval cell proliferation in the IL-6 ؊/؊ mice, as determined by routine histology and AFP mRNA analysis, and non-oval BEC proliferation was also slightly impaired in the IL-6 ؊/؊ mice compared with the IL-6 ؉/؉ mice. In addition, liver DNA content per gram of liver showed an increase compared with normal at 60 hours in both groups, but by 96 hours, there was no difference between the two groups. Thus, neither oval cell nor BEC proliferation, nor hepatocyte hypertrophy, could account for the eventual equivalent weight recovery. There was, however, a difference between the two groups in the rate of apoptosis. In normal livers of both IL-6 ؊/؊ and IL-6 ؉/؉ mice, apoptotic cells were uncommon, and even fewer such cells were detected at 24, 36, and 48 hours after PH. Between 60 and 96 hours after PH, a wave of apoptosis spread through the livers of both groups. The number of apoptotic cells was directly proportional to the magnitude of hepatocyte BrdU labeling and liver DNA content after PH, and the difference between the nadir of apoptosis at 24 hours and the peak at 96 hours was greater for the IL-6 ؉/؉ mice. In addition, a direct comparison between the two groups at 96 hours showed that hepatocyte apoptosis was significantly lower in the IL-6 ؊/؊ versus the IL-6 ؉/؉ mice (P F .02). Treatment of the IL-6 ؊/؊ mice with rIL-6 completely r...

The interleukin-6 (IL-6)/gp-80 and hepatocyte growth factor (HGF)/met ligand/receptor systems have been shown to stimulate biliary epithelial cell (BEC) DNA synthesis in vitro. The mRNA and protein production of these two in vitro mitogens were mapped in vivo during the first week after bile duct ligation (BDL) when peak BEC DNA synthesis is seen. Changes around the biliary tree were compared with those seen in the peripheral liver using a combination of Northern blotting and a unique biliary tree isolation technique, in which the bile ducts and the surrounding portal stroma and inflammatory cells are separated from the hepatocytes by perfusion digestion. Further localization was performed with in situ hybridization and immunohistochemistry. In the normal liver, there is low-level expression of HGF mRNA by periportal stellate cells, and HGF protein localizes to these cells and to neutrophils; extracellular HGF protein is present in the bile. There is no detectable IL-6 mRNA by Northern analysis or IL-6 protein expression in the normal liver, but both met and IL-6 receptor (IL-6R) mRNA are detectable; met mRNA is expressed strongly in the biliary tree, and met protein is expressed weakly on hepatocytes and strongly on BEC. IL-6R mRNA is weakly expressed in the biliary tree, and IL-6R protein is detectable on hepatocytes, with a periportal-to-perivenular gradient, but not on BEC. During the first 3 days after BDL, HGF mRNA expression is increased in both the biliary tree and in the peripheral liver, and production is localized to stellate cells, periductal neutrophils, and stromal cells, which typically accompany the proliferating ductules. IL-6 mRNA and protein were detected only near the biliary tree after BDL, and not in the peripheral liver, and the production was localized to periductal hematolymphoid cells, which had the morphological appearance of macrophages and/or dendritic cells. There is also a distinct up-regulation of met and gp-80 mRNA and protein in the biliary tree, which is stronger than that seen in the peripheral liver. Met protein expression is increased, and IL-6R(gp-80) protein is induced on the proliferating BEC, consistent with the participation of both the HGF/met and IL-6/gp-80 systems in the early phases of type I ductular reactions. These observations show that periductal hematolymphoid and stromal cells are the source of BEC growth factors, and receptors for these factors are up-regulated on BEC during active ductular proliferation. Complex interactions between the inflammatory, stromal, and BEC results in a dysmorphogenic repair response that eventually leads to cirrhosis. (HEPATOLOGY 1998;28:1260-1268.)

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Abstract:We report on the high power amplification of 1064nm linearlypolarized laser in all-fiber polarization-maintained MOPA, which can operate at output power level of 1.3kW. The main amplifier was pumped with six 915nm laser diodes, and the slope efficiency is 65.3%. The beam quality (M 2 ) was measured to be <1.2 at full power operation. The polarization extinction rate of the fiber amplifier was measured to be above 94% before mode instabilities (MI) sets in, which reduced to about 90% after the onset of MI. Power scaling capability of strategies for suppressing MI is analyzed based on a novel semi-analytical model, the theoretical results of which agree with the experimental results. It shows that mitigating MI by coiling the gain fiber is an effective and practical way in standard double-cladding large mode area fiber, and, by tight coiling of the gain fiber to the radius of 5.5cm, the MI threshold can be increased to 3 times higher than that without coiling or loose coiling. Experimental study has been carried out to verify the idea, which has proved that MI was suppressed successfully in the amplifier by tight coiling.