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Background Paclitaxel is a widely prescribed chemotherapy drug for treating solid tumors. However, paclitaxel-induced peripheral neuropathy (PIPN) is a common adverse effect during paclitaxel treatment, which results in sensory abnormalities and neuropathic pain among patients. Unfortunately, the mechanisms underlying PIPN still remain poorly understood. Long noncoding RNAs (lncRNAs) are novel and promising targets for chronic pain treatment, but their involvement in PIPN still remains unexplored. Methods We established a rat PIPN model by repetitive paclitaxel application. Immunostaining, RNA sequencing (RNA-Seq) and bioinformatics analysis were performed to study glia cell activation and explore lncRNA/mRNA expression profiles in spinal cord dorsal horn (SCDH) of PIPN model rats. qPCR and protein assay were used for further validation. Results PIPN model rats developed long-lasting mechanical and thermal pain hypersensitivities in hind paws, accompanied with astrocyte and microglia activation in SCDH. RNA-Seq identified a total of 814 differentially expressed mRNAs (DEmRNA) (including 467 upregulated and 347 downregulated) and 412 DElncRNAs (including 145 upregulated and 267 downregulated) in SCDH of PIPN model rats vs. control rats. Functional analysis of DEmRNAs and DElncRNAs identified that the most significantly enriched pathways include immune/inflammatory responses and neurotrophin signaling pathways, which are all important mechanisms mediating neuroinflammation, central sensitization, and chronic pain. We further compared our dataset with other published datasets of neuropathic pain and identified a core set of immune response-related genes extensively involved in PIPN and other neuropathic pain conditions. Lastly, a competing RNA network analysis of DElncRNAs and DEmRNAs was performed to identify potential regulatory networks of lncRNAs on mRNA through miRNA sponging. Conclusions Our study provided the transcriptome profiling of DElncRNAs and DEmRNAs and uncovered immune and inflammatory responses were predominant biological events in SCDH of the rat PIPN model. Thus, our study may help to identify promising genes or signaling pathways for PIPN therapeutics.

Abstract Background Nearly 20% novel coronavirus disease 2019 (COVID-19) patients have abnormal coagulation function. Padua prediction score (PPS) is a validated tools for venous thromboembolism (VTE) risk assessment. However, its clinical value in COVID-19 patients evaluation was unclear. Methods We prospectively evaluated the VTE risk of COVID-19 patients using PPS. Demographic and clinical data were collected. Association of PPS with 28-days mortality was analyzed by multivariate logistic regression and Kaplan-Meier analysis. Results 274 continuous patients were enrolled, with total mortality of 17.2%. Patients in high PPS group, with significantly abnormal coagulation, have a higher levels of interleukin 6 (25.27 pg/ml vs.2.55 pg/ml, P < 0.001), prophylactic anticoagulation rate (60.7% vs. 6.5%, P<0.001) and mortality (40.5% vs. 5.9%, P<0.001) as compared with that in low PPS group. Critical patients showed higher PPS (6 score vs. 2 score, P<0.001) than that in severe patients. Multivariate logistic regression revealed the independent risk factors of in-hospital mortality included high PPS (OR: 7.35, 95%CI: 3.08 - 16.01), increased interleukin-6 (OR: 11.79, 95%CI: 5.45 - 26.20) and elevated d-dimer (OR: 4.65, 95%CI: 1.15 - 12.15). Kaplan-Meier analysis indicated patients with higher PPS had a significant survival disadvantage. Prophylactic anticoagulation in higher PPS patients show a mild advantage of mortality but without statistical significance (37.1% vs. 45.7%, P=0.42). Conclusion Higher PPS associated with in-hospital poor prognosis in COVID-19 patients. Prophylactic anticoagulation showed a mild advantage of mortality in COVID-19 patients with higher PPS, but it remain need further investigation.

49Background and Aims: Cumulating observations have indicated that patients with 50 coronavirus disease undergo different patterns of liver impairment. We 51 performed a meta-analysis of published liver manifestations and described the liver 52 damage in Methods: We searched PubMed, Google Scholar, Embase, Cochrane Library, 54 medRxiv, bioRxiv, and three Chinese electronic databases through April 18, 2020, in 55 accordance with the Preferred Reporting Items for Meta-Analyses. We analyzed 56 pooled data on liver chemistries stratified by COVID-19 severity using a fixed or 57 random-effects model. 58Results: In the meta-analysis of 37 studies, which included a total of 6,235 patients, 59 the pooled mean alanine aminotransferase (ALT) was 36.4 IU/L in the severe 60 COVID-19 cases and 27.8 IU/L in the non-severe cases (95% confidence interval [CI]: 61 −9.4 to −5.1, p < 0.0001). The pooled mean aspartate aminotransferase (AST) was 62 46.8 IU/L in the severe cases and 30.4 IU/L in the non-severe cases (95% CI: −15.1 to 63 −10.4, p < 0.0001). Furthermore, regardless of disease severity, the AST level is often 64higher than the ALT level. Compared with the non-severe cases, the severe cases 65 tended to have higher γ-glutamyltransferase levels but lower albumin levels. 66Conclusions: In this meta-analysis, we comprehensively described three patterns of 67 liver impairment related to COVID-19, namely hepatocellular injury, cholestasis, and 68 hepatocellular disfunction, according to COVID-19 severity. Patients with abnormal 69 liver test results are at higher risk of progression to severe disease. Close monitoring 70 of liver chemistries provides an early warning against disease progression. 71 72

Complex regional pain syndrome type-I (CRPS-I) is chronic neurological disorder accompanied with devastating pain. Most conventional medical treatments lack effectiveness, making CRPS-I a challenging clinical condition. Electroacupuncture (EA) showed effectiveness in alleviating the pain symptoms of CRPS-I patients. However, the molecular mechanisms underlying EA's therapeutic effect are still not well-understood. Here, we established the rat chronic post-ischemic pain (CPIP) model to mimic CRPS-I and performed repetitive EA on bilateral hind limbs of the CPIP model rats. We then performed RNA-sequencing (RNA-Seq) to study the differences in gene expression, gene networks, and molecular pathways in ipsilateral DRGs innervating the hind limb of the CPIP model rats with and without repetitive EA treatment. Our results found that repetitive EA treatment significantly alleviated mechanical allodynia in bilateral hind limbs of CPIP model rats. RNA-Seq analysis indicated that EA modulated the expression of multiple genes and gene networks in the DRGs of CPIP model rats. Further bioinformatics analysis identified the up-regulation of an array of genes involved in biological process such as neutrophil chemotaxis and immune response in the DRGs of CPIP model rats after EA treatment. Thus, these results suggest that EA may alleviate pain response in CPIP model rats via regulating multiple genes. Our work may help to further advance the understandings of the molecular mechanisms underlying EA's therapeutic effects on CRPS-I and help to identify novel targets for CRPS-I treatment.

Although abnormal liver chemistries are linked to a higher risk of coronavirus disease 2019 (COVID-19)-related death, liver manifestations may be diverse and even confusing. Thus, we performed a meta-analysis of published liver manifestations and described the liver damage in patients with COVID-19 who died or discharged alive. We searched PubMed, Google Scholar, medRxiv, bioRxiv, the Cochrane Library, Embase, and three Chinese electronic databases through April 22, 2020. We analyzed pooled data on liver chemistries stratified by the main clinical outcome of COVID-19, using a fixed or random-effects model. In our meta-analysis of 19 studies, which included a total of 4,103 patients, the pooled mean alanine aminotransferase and aspartate aminotransferase levels were, respectively, 31.7 IU/L and 51.0 IU/L in the patients with COVID-19 who died and 27.7 IU/L and 32.9 IU/L in those discharged alive (both P < 0.0001). Compared with the patients discharged alive, those who died tended to have lower albumin levels but longer prothrombin time and higher international normalized ratio. Conclusion: In this meta-analysis, according to the main clinical outcome of COVID-19, we comprehensively describe three patterns of liver impairment related to COVID-19: hepatocellular injury, cholestasis, and hepatocellular disfunction. The patients who died from COVID-19 tended to have different liver chemistries from those discharged alive. Special caution should be given to the patients with a relatively higher index of liver chemistries. (Hepatology Communications 2020;0:1-12). C oronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a nonsegmented positive-sense RNA virus with an envelope belonging to the family Coronaviridae. The coronavirus is widely distributed in humans and other mammals. In the past 20 years, the coronavirus has caused several localized epidemics and even global pandemics, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the ongoing COVID-19 pandemic. Worldwide, the spread and upward trend of COVID-19 have accelerated dramatically. According to the situation report released by the World Health Organization (WHO), as of April 25, 2020, 2,719,897 COVID-19 cases were confirmed globally, with a fatality rate of 6.9%. (1) In response to the emerging threat, the WHO declared a Public Health Emergency of International Concern

49Background and Aims: Although abnormal liver chemistries are linked to higher 50 risk of death related to coronavirus disease , liver manifestations may be 51 diverse and even confused. Thus, we performed a meta-analysis of published liver 52 manifestations and described the liver damage in COVID-19 patients with death or 53 survival. 54Methods: We searched PubMed, Google Scholar, medRxiv, bioRxiv, Cochrane 55 Library, Embase, and three Chinese electronic databases through April 22, 2020. We 56 analyzed pooled data on liver chemistries stratified by the main clinical outcome of 57 COVID-19 using a fixed or random-effects model. 58Results: In the meta-analysis of 18 studies, which included a total of 2,862 patients,

Background: Mirror-image pain (MIP), which develops from the healthy body region contralateral to the actual injured site, is a mysterious pain phenomenon accompanying many chronic pain conditions, such as complex regional pain syndrome (CRPS). However, the pathogenesis of MIP still remains largely unknown. The purpose of this study is to perform an expression profiling to identify genes related to MIP in an animal model of CRPS-I. Methods: We established a rat chronic post-ischemic pain (CPIP) model to mimic human CRPS-I. RNA-sequencing (RNA-Seq), bioinformatics, qPCR, immunostaining, and animal behavioral assays were used to screen potential genes in the contralateral dorsal root ganglia (DRG) that may be involved in MIP. Results: The CPIP model rats developed robust and persistent MIP in contralateral hind paws. Bilateral DRG neurons did not exhibit obvious neuronal damage. RNA-Seq of contralateral DRG from CPIP model rats identified a total 527 differentially expressed genes (DEGs) vs sham rats. The expression changes of several representative DEGs were further verified by qPCR. Bioinformatics analysis indicated that the immune system process, innate immune response, and cell adhesion were among the mostly enriched biological processes, which are important processes involved in pain sensitization, neuroinflammation, and chronic pain. We further identified DEGs potentially involved in pain mechanisms or enriched in small-to medium-sized sensory neurons or TRPV1-lineage nociceptors. By comparing with published datasets summarizing genes enriched in pain mechanisms, we sorted out a core set of genes which might contribute to nociception and the pain mechanism in MIP. Conclusion:We provided by far the first study to profile gene expression changes and pathway analysis of contralateral DRG for the studying of MIP mechanisms. This work may provide novel insights into understanding the mysterious mechanisms underlying MIP.