Highlights COVID -19 cases now confirmed in multiple countries. assessed the prevalence of comorbidities in infected patients.  comorbidities are risk factors for severe patients compare with Non-severe.J o u r n a l P r e -p r o o f 2  help the health sector guide vulnerable populations and assess the risk of deterioration.Background: An outbreak of Novel Coronavirus in Wuhan, China, the epidemic is more widespread than initially estimated, with cases now confirmed in multiple countries. Aims:The aim of the meta-analysis was to assess the prevalence of comorbidities in the COVID-19 infection patients and the risk of underlying diseases in severe patients compared to non-severe patients. Methods:A literature search was conducted using the databases PubMed, EMBASE, and Web of sciences until February 25, 2020. Risk ratio (OR) and 95% confidence intervals (CIs) were pooled using random-effects models.Results: Eight studies were included in the meta-analysis, including 46248 infected patients. The result showed the most prevalent clinical symptom was fever ( 91±3, 95% CI 86-97% ), followed by cough (67±7, 95% CI 59-76%), fatigue ( 51±0, 95% CI 34-68% ) and dyspnea ( 30±4, 95% CI 21-40%). The most prevalent comorbidity were hypertension (17±7, 95% CI 14-22%) and diabetes ( 8±6, 95% CI 6-11% ), followed by cardiovascular diseases ( 5±4, 95% CI 4-7% ) and respiratory system disease( 2±0, 95% CI 1-3% ). Compared with the Non-severe patient, the pooled odds ratio of hypertension, respiratory system disease, cardiovascular disease in severe patients were (OR 2.36, 95% CI: 1.46-3.83) ,(OR 2.46, 95% CI: 1.76-3.44) and (OR 3.42, 95% CI: 1.88-6.22)respectively. Conclusion:We assessed the prevalence of comorbidities in the COVID-19 infection patients and found underlying disease, including hypertension, respiratory system disease and cardiovascular, may be a risk factor for severe patients compared with Non-severe patients.

Connexin 43 (Cx43), a vital gap junction protein in tumor microenvironment (TME), is a novel molecular target for melanoma chemotherapeutics due to its tumor suppressive function. Dioscin, an herbal steroidal saponin, exerts anti-tumor effects while the underlying mechanism is unclear. Using WB, FACS, and immunofluorescence methodologies, we found dioscin significantly activated the transcription and translation of Cx43 via the retinoid acid signaling pathway and simultaneously enhanced the transporting function of Cx43. Through stimulating Cx43, dioscin remarkably suppressed the migratory and invasive capacities of B16 cells, and notably decreased pluripotency markers of cancer stem cells and epithelial-to-mesenchymal transition in B16 cells and animal tumor tissues. Conversely, dioscin improved the secretion of pro-inflammatory cytokines (IL-6, TNFα, and IL-1β), and the phagocytic capacity of tumor-associated macrophages by increasing M2-to-M1 phenotype transition. More strikingly, even in Cx43 functional deficient B16 and RAW264.7 cells, dioscin still dramatically reversed the aggravated tumor malignancy and reduced macrophage phagocytic activity. Two classical metastasis animal models were utilized in vivo and results showed that dioscin showed significant anti-metastatic effects, which is closely related to the expression of Cx43 either in in situ tumor or metastatic lung nodes. In conclusion, dioscin targets Cx43 to suppress the tumor cell malignancy and activate macrophage sensitivity, thereby targeting melanoma microenvironment.

Background: Acute myocardial infarction (AMI) is a common disease leading threat to human health around the world. Here we aimed to explore new biomarkers and potential therapeutic targets in AMI through adopting integrated bioinformatics tools. Methods: The gene expression Omnibus (GEO) database was used to obtain genes data of AMI and no-AMI whole blood. Furthermore, differentially expressed genes (DEGs) were screened using the “Limma” package in R 3.6.1 software. Functional and pathway enrichment analyses of DEGs were performed via “Bioconductor” and “GOplot” package in R 3.6.1 software. In order to screen hub DEGs, the STRING version 11.0 database, Cytoscape and molecular complex detection (MCODE) were applied. Correlation among the hub DEGs was evaluated using Pearson's correlation analysis. Results: By performing DEGs analysis, 289 upregulated and 62 downregulated DEGs were successfully identified from GSE66360, respectively. And they were mainly enriched in the terms of neutrophil activation, immune response, cytokine, nuclear factor kappa-B (NF-κB) signaling pathway, IL-17 signaling pathway, and tumor necrosis factor (TNF) signaling pathway. Based on the data of protein–protein interaction (PPI), the top 10 hub genes were ranked, including interleukin-8 (CXCL8), TNF, N-formyl peptide receptor 2 (FPR2), growth-regulated alpha protein (CXCL1), transcription factor AP-1 (JUN), interleukin-1 beta (IL1B), platelet basic protein (PPBP), matrix metalloproteinase-9 (MMP9), toll-like receptor 2 (TLR2), and high affinity immunoglobulin epsilon receptor subunit gamma (FCER1G). What's more, the results of correlation analysis demonstrated that there was positive correlation between the 10 hub DEGs. Conclusion: Ten DEGs were identified as potential candidate diagnostic biomarkers for patients with AMI in present study. However, further experiments are needed to confirm the functional pathways and hub genes associated with AMI.

Lung adenocarcinoma (LAC), predominant subclassfication of lung cancer, leads high incidence and mortality annually worldwide. During the premalignant transition from lung adenomas to LAC, cellular senescence is regard as a critical physiological barrier against tumor progression. Nevertheless, the role of senescence in tumorigenesis is controversial and few senescence inducers are extensively determined. In this study, we used two classical cell lines A549 and H1299 and two NSCLC xenograft models on Balb/c-nude mice to reveal the pro-senescence effects of shikonin and the corresponding underlying mechanism in LAC. Shikonin, a pure compound isolated from the herbal medicine Lithospermum erythrorhizon, remarkably stimulated cellular senescence including increased SAHF formation, enlarged cellular morphology, and induced SA-β-Gal positive staining. Further mechanism study revealed that the pro-senescence effect of shikonin was dependent on the increased intercellular ROS generation, which subsequently triggered DNA damage-p53/p21waf axis without activating oncogenes such as Ras and MEK-1. Meanwhile, Kdm2b, an H3K36me2-specific demethylase effectively suppressed ROS generation, was also notably suppressed by shikonin treatment. Moreover, shikonin at 10 mg/kg significantly inhibited tumor weights by 55.84% and 50.98% in A549 and H1299 xenograft model, respectively (P < 0.05) through activating cellular senescence. Our study suggested that shikonin, a ROS-dependent senescence inducer, could serve as a promising agent for further lung cancer treatment.

The tumor suppressor protein p53 plays an important role in the development and progression of colon cancer, and the subcellular organelle localization directly affects its function. Wogonin (5,7-dihydroxy-8-methoxyflavone), a mono-flavonoid extracted from root of Scutellaria baicalensis Georgi, possesses acceptable toxicity and has been used in colorectal cancer (CRC) chemoprevention in pre-clinical trials by oncologist. However, the underlying anti-colon cancer mechanisms of wogonin are not yet fully understood. In the present study, the effect of wogonin on the initiation and development of colitis-associated cancer through p53 nuclear translocation was explored. AOM-DSS CRC animal model and human CRC HCT-116 cell model were used to evaluate the in vivo and in vitro anti-colon cancer action of wogonin. We observed that wogonin showed a dramaticlly preventive effect on colon cancer. Our results showed that wogonin caused apoptotic cell death in human CRC HCT-116 cell through increased endoplasmic reticulum (ER) stress. Meanwhile, excessive ER stress facilitated the cytoplasmic localization of p53 through increasing phosphor-p53 at S315 and S376 sites, induced caspase-dependent apoptosis and inhibited autophagy. Furthermore, we verified the chemoprevention effect and toxicity of wogonin in vivo by utilizing an AOM-DSS colon cancer animal model. We found that wogonin not only reduced tumor multiplicity, preserved colon length to normal (6.79 ± 0.34 to 7.41 ± 0.56, P < 0.05) but also didn’t induce side effects on various organs. In conclusion, these results explain the anti-tumor effect of wogonin in CRC and suggest wogonin as a potential therapeutic candidate for the therapeutic strategy in CRC treatment.

Objective This study compared Chinese herbal injections (CHIs) plus chemotherapy with chemotherapy alone in terms of clinical efficacy and safety for treating patients with esophageal cancer (EC). Methods Randomized controlled trials (RCTs) of CHIs combined with chemotherapy for treating EC published in English and Chinese databases were identified. The main outcomes were clinical efficacy, performance status, and adverse reactions. Random-effects models were fitted to calculate the odds ratios and 95% confidence intervals for all pair-wise comparisons. Results In total, 29 RCTs of eight CHIs were included in this study. The results of cluster analysis demonstrated that Compound Kushen injection plus chemotherapy was the optimal choice for improving the clinical efficacy rate. Shenfu injection was associated with a relatively high performance status. Compound Kushen injection and Shenfu injection were inferior to other CHIs in terms of preventing leukopenia and gastrointestinal side effects. Conclusions The combination of Compound Kushen injection with chemotherapy could improve efficacy and reduce adverse drug reactions versus chemotherapy alone in patients with EC.

Sinomenine hydrochloride (SH) is an ideal drug for the treatment of rheumatoid arthritis and osteoarthritis. However, high plasma concentration of systemically administered SH can release histamine, which can cause rash and gastrointestinal side effects. Topical delivery can increase SH concentration in the synovial fluid without high plasma level, thus minimizing systemic side effects. However, passive diffusion of SH was found to be inefficient because of the presence of the stratum corneum layer. Therefore, an effective method is required to compensate for the low efficiency of SH passive diffusion. In this study, transdermal experiments in vitro and clinical tests were utilized to explore the optimized parameters for electroporation of topical delivery for SH. Fluorescence experiment and hematoxylin and eosin staining analysis were performed to reveal the mechanism by which electroporation promoted permeation. In vitro, optimized electroporation parameters were 3 KHz, exponential waveform, and intensity 10. Using these parameters, transdermal permeation of SH was increased by 1.9–10.1 fold in mice skin and by 1.6–47.1 fold in miniature pig skin compared with passive diffusion. After the electroporation stimulation, the intercellular intervals and epidermal cracks in the skin increased. In clinical tests, SH concentration in synovial fluid was 20.84 ng/mL after treatment with electroporation. Therefore, electroporation with optimized parameters could significantly enhance transdermal permeation of SH. The mechanism by which electroporation promoted permeation was that the electronic pulses made the skin structure looser. To summarize, electroporation may be an effective complementary method for transdermal permeation of SH. The controlled release of electroporation may be a promising clinical method for transdermal drug administration.

In this paper, we investigate the performance of the non-orthogonal multiple access (NOMA) system with incremental relaying, where the relay is employed with amplify-and-forward (AF) or decode-and-forward (DF) protocols. To characterize the outage behaviors of the incremental cooperative NOMA (ICN) system, new closed-form expressions of both exact and asymptotic outage probability for two users are derived. In addition, the performance of the conventional cooperative NOMA (CCN) system is analyzed as a benchmark for the the purpose of comparison. We confirm that the outage performance of the distant user is enhanced when ICN system is employed. Numerical results are presented to demonstrate that (1) the near user of the ICN system achieves better outage behavior than that of the CCN system in the low signal-to-noise ratio (SNR) region; (2) the outage performance of distant user for the DF-based ICN system is superior to that of the AF-based ICN system when the system works in cooperative NOMA transmission mode; and (3) in the low SNR, the throughput of the ICN system is higher than that of the CCN system. authors of [9] have researched the performance of a downlink single-cell NOMA network when assuming imperfect channel state information (CSI) and second-order statistics. Furthermore, the authors in [10] consider the scenario that each user only feedback one bit of its CSI to a base station (BS) and analyzed the outage performance. Apart from these researches, there are a lot of studies on improving the secrecy performance of multiple users [11,12], where the external and internal eavesdropping scenarios have been considered. Up to now, NOMA has been extended to cooperative communication systems [13, 14], as the higher diversity and extended coverage can be obtained in wireless networks. The authors have analyzed the outage performance of NOMA system with decode and forward (DF) relay employing full-duplex (FD) and half-duplex (HD) mode, where the near user was selected as a relay to deliver information and improve transmission reliability of distance users [15]. Inspired by this, simultaneous wireless information and