Objective: Coronavirus Disease 2019 (COVID-19) is a pandemic. This systematic review compares mortality risk factors including clinical, demographic and laboratory features of COVID-19, Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The aim is to provide new strategies for COVID-19 prevention and treatment. Methods: We performed a systematic review with meta-analysis, using five databases to compare the predictors of death for COVID-19, SARS and MERS. A random-effects model meta-analysis calculated odds ratios (OR) and 95% confidence intervals (95% CI). Results: 845 articles up through 11/4/2020 were retrieved, but only 28 studies were included in this meta-analysis. The results showed that males had a higher likelihood of death than females (OR = 1.82, 95% CI 1.56-2.13). Age (OR = 7.86, 95% CI 5.46-11.29), diabetes comorbidity (OR = 3.73, 95% CI 2.35-5.90), chronic lung disease (OR = 3.43, 95% CI 1.80-6.52) and hypertension (OR = 3.38, 95% CI 2.45-4.67) were the mortality risk factors. The laboratory indicators lactic dehydrogenase (OR = 37.52, 95% CI 24.68-57.03), C-reactive protein (OR = 12.11, 95% CI 5.24-27.98), and neutrophils (OR = 17.56, 95% CI 10.67-28.90) had stronger correlations with COVID-19 mortality than with SARS or MERS mortality. Consolidation and ground-glass opacity imaging features were similar among COVID-19, SARS, and MERS patients. Conclusions: COVID-19 s mortality factors are similar to those of SARS and MERS. Age and laboratory indicators could be effective predictors of COVID-19 mortality outcomes.

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Matrine is a component of the traditional Chinese medical herb Sophora flavescens Ait, which is widely used to treat diseases such as viral hepatitis, cardiac arrhythmia and skin inflammations. As indicated by previous reports, the molecular mechanism of matrine's anti-cancer effect has been poorly clarified. In this study, we used both in vitro and in vivo models to investigate matrine's antitumor effect and its possible molecular mechanisms. Murine hepatocellular carcinoma H22 cells were cultured in the presence of matrine at various concentrations (0.2 - 2.0 mg/mL). A dose-dependent antiproliferation effect was observed. The 50 % inhibitory concentration (IC (50)) was 0.6 mg/mL. Antiproliferation effects of matrine were associated with an increase in cells arrested in the G (1) phase of the cell cycle. Morphological changes, flow cytometric analysis and expression of the proapoptotic protein Bax indicated that this anticancer effect was mediated via apoptosis. In vivo antitumor efficacy was evaluated following S. C. inoculation of H22 cells in BALB/c mice. Matrine administrated I. P. resulted in strong in vivo anticancer activity. Our results showed that seven doses of matrine at 50 mg/kg/dose inhibited 60.7 % of tumor growth. Transmission electron microscope (TEM) analysis and histoimmunochemical staining for Bcl-2 and Bax proteins also indicated induction of apoptosis in tumor tissues by matrine. Taken together, our results demonstrate that matrine possesses strong antitumor activities in vitro and in vivo. Inhibition of cell proliferation and induction of apoptosis are the likely mechanisms responsible for matrine's antitumor activities.

Background: Absolute handgrip strength has been correlated with metabolic profile and metabolic disease. Whether relative handgrip strength is also associated with metabolic disease has not been assessed. This study aimed at assessing the association of relative handgrip strength with metabolic profile and metabolic disease in the general population in China.Methods: Data were derived from an ongoing cross-sectional survey of the 2013 National Physical and Health in Shanxi Province, which involved 5520 participants. Multiple linear regression or multiple logistic regression analysis were used to assess the association of absolute/relative handgrip strength with the metabolic profile, preclinical, and established stages of metabolic diseases.Results: This study revealed that relative handgrip strength, that is when normalized to BMI, was associated with: (1) in both genders for more favorable blood lipid levels of high-density lipoprotein cholesterol [males: b = 0.19 (0.15, 0.23); females: b = 0.22 (0.17, 0.28)], low-density lipoprotein cholesterol [males: b = −0.14 (−0.23, −0.05); females: b = −0.19 (−0.31, −0.18)], triglycerides [males: b = −0.58 (−0.74, −0.43); females: b = −0.55 (−0.74, −0.36)] and total cholesterol [males: b = −0.20 (−0.31, −0.10); females: b = −0.19 (−0.32, −0.06)]; and better serum glucose levels in males [b = −0.30 (−0.46, −0.15)]. (2) lower risk of impaired fasting glucose in males {third quartile [OR = 0.66 (0.45–0.95)] and fourth quartile [OR = 0.46 (0.30–0.71)] vs. first quartile} and dyslipidemia in both genders {third quartile [males: OR = 0.65 (0.48–0.87); females: OR = 0.68 (0.53–0.86)] and fourth quartile [males: OR = 0.47 (0.35–0.64); females: OR = 0.47(0.36–0.61)] vs. first quartile}. (3) lower risk of hyperlipidemia in both genders third quartile [males: OR = 0.66 (0.50–0.87); females: OR = 0.57 (0.43–0.75)] and fourth quartile [males: OR = 0.35 (0.26–0.47); females: OR = 0.51 (0.38–0.70)] vs. first quartile. However, contrary to relative handgrip strength, higher absolute handgrip strength was associated with unfavorable metabolic profiles and higher risk of metabolic diseases. These paradoxical associations were retained even after adjusted for BMI by employed a multivariate analysis.Conclusion: We conclude that measurement of relative handgrip strength can be used as a reasonable clinical predictor of metabolic health and disease.

Background Micro- and nanoplastic pollution has become a global environmental problem. Nanoplastics in the environment are still hard to detect because of analysis technology limitations. It is believed that when microplastics are found in the environment, more undetected nanoplastics are around. The current “microplastic exposure” is in fact the mixture of micro- and nanoplastic exposures. Therefore, the biological interaction between organisms among different sizes of micro- and nanoplastics should not be neglected. Results We measured the biodistribution of three polystyrene (PS) particles (50 nm PS, PS50; 500 nm PS, PS500; 5000 nm PS, PS5000) under single and co-exposure conditions in mice. We explored the underlying mechanisms by investigating the effects on three major components of the intestinal barrier (the mucus layer, tight junctions and the epithelial cells) in four intestine segments (duodenum, jejunum, ileum and colon) of mice. We found that the amounts of both PS500 and PS5000 increased when they were co-exposed with PS50 for 24 h in the mice. These increased amounts were due primarily to the increased permeability in the mouse intestines. We also confirmed there was a combined toxicity of PS50 and PS500 in the mouse intestines. This manifested as the mixture of PS50 and PS500 causing more severe dysfunction of the intestinal barrier than that caused by PS50 or PS500 alone. We found that the combined toxicity of PS micro- and nanoplastics on intestinal barrier dysfunction was caused primarily by reactive oxygen species (ROS)-mediated epithelial cell apoptosis in the mice. These findings were further confirmed by an oxidants or antioxidants pretreatment study. In addition, the combined toxicity of PS micro- and nanoplastics was also found in the mice after a 28-day repeated dose exposure. Conclusions There is a combined toxicity of PS50 and PS500 in the mouse intestines, which was caused primarily by ROS-mediated epithelial cell apoptosis in the mice. Considering that most recent studies on PS micro- and nanoplastics have been conducted using a single particle size, the health risks of exposure to PS micro- and nanoplastics on organisms may be underestimated.

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It is reported that matrine, one of the major effective compounds isolated from the root of Sophora flavescens Ait., has anti-leukemia activity. In this study, we find that the treatment of leukemia U937 cells with matrine results in induction of apoptosis. Analysis of the mechanism underling this apoptotic event showed activation of caspases-9, -3, and -7, and release of cytochrome C from mitochondria to cytosol, and cleavage of poly(ADP-ribose) polymerase. Matrine did not alter the level of bcl-2 and bcl-xL as well as bax. In addition, no correlation was found between matrine administration and activation of the three major MAPK subfamilies (Erk1/2, p38, JNK/SAPK). The results indicate that matrine induces apoptosis in U937 cells via a cytochrome C-triggered caspase activation pathway.

Abstract:The dry root of Sophora flavescens Ait. (SF) has long been used in a variety of Chinese herbal formulations to treat patients with cancer. Alkaloids are commonly known to present in SF as main active constituents. Here, we report that among the six characterized SF-derived quinolizidine alkaloids including sophoridine, aloperine, sophocarpine, matrine, oxymatrine and cytisine, aloperine exerted the most potent in vitro cytotoxic activity against the human cancer cell lines and oxymatrine exhibited selective anti-cancer activity against hepatocellular carcinoma HepG2 cells. Analysis of DNA fragmentation and PARP cleavage revealed that aloperine treatment for 48 hr induced apoptosis in HL-60 cells. In addition, autophagic formation of acidic vacuole was also observed in HL-60 cells exposed to aloperine. These results suggest that aloperine may be a novel contributor to the anti-cancer properties of SF.The dry root of Sophora flavescens Ait. (SF) (Leguminosae), also referred to as Kushen, has a long history of use in a variety of traditional Chinese medicine herbal formulations to treat a range of diseases, including cancer, viral hepatitis, cardiac arrhythmia and skin diseases [1-4]. As higher percentage of alkaloids is found in SF (3.3%), SF alkaloids have received much attention in the past decades in China as the bioactive substances [5,6]. For example, SF alkaloids are demonstrated to be the potential chemopreventive and chemotherapeutic agents, and they contribute to the therapeutic anti-cancer activity of SF. Alkaloids injection prepared from SF has been approved to treat patients with cancer by the Chinese State Food and Drug Administration (SFDA) in 1992. Clinical studies have demonstrated that the injection is a safe and effective remedy for the treatment of various types of cancer [7,8].Quinolizidine alkaloids have been identified to be the major components of SF alkaloids [9]. Quinolizidine alkaloids represent about 2% of the known alkaloids from plants [10], and most of them were initially noticed as constituents of plants poisonous to humans and livestock. However, accumulated evidence indicates that some of them exhibit potentially useful pharmacological properties like anti-cancer, anti-bacterium, anti-virus, anti-inflammation and pain relief [11]. Quinolizidine alkaloids can be divided into more than six structural groups such as matrine-type, aloperinetype and cytisine-type. Matrine-type alkaloids such as matrine, oxymatrine, sophocarpine and sophoridine are commonly purified from SF [9]. Although previous studies demonstrate that matrine-type alkaloids mediate growth inhibition in different types of cancer cells, the reported IC 50 values are generally not lower than 0.5 mM [12][13][14][15][16]. It seems that the alkaloids other than matrine-type may contribute to the anti-neoplastic activities of SF alkaloids. Previous reports indicate that both aloperine and cytisine are also the characterized components in SF [9,17,18], but inspection of the literature data reveals that the potential ...