Comparison of laboratory parameters in mild vs. severe cases and died vs. survived patients with COVID-19: systematic review and meta-analysis.

Background: This study aimed to summarize the available data on the association between the severity of (COVID-19) and routine blood indicators, inflammatory, biochemical parameters and coagulation parameter. Methods: A literature search was conducted of PubMed, EMBASE, and Web of Sciences, CNKI, WanFang database providing relevant data. Random-effects meta-analysis was used to pool effect sizes. Results: In patients with severe symptoms, interleukin-6, [IL-6; standardized mean difference (SMD) =1.15, 95% confidence interval (95% CI): 1.01, 1.29, P<0.001, n=1,121], interleukin-10 (IL-10; SMD =0.92, 95% CI: 0.75, 1.08, P<0.001, n=782), interleukin-4 (IL-4; SMD =0.2, 95% CI: 0.01, 0.39, P=0.04, n=500), procalcitonin (PCT; SMD =1.16, 95% CI: 0.99, 1.33, P<0.001, n=734), C-reactive protein (CRP; SMD =1.42, 95% CI: 1.27, 1.57, P<0.001, n=1,286), serum amyloid A (SAA; SMD =2.82, 95% CI: 2.53, 3.11, P<0.001, n=502) neutrophil count (SMD =0.63, 95% CI: 0.44, 0.82, P<0.001, n=558), alanine aminotransferase (ALT; SMD =2.72, 95% CI: 2.43, 3.02, P<0.001, n=538), aspartate aminotransferase (AST; SMD =2.75, 95% CI: 2.37, 3.12, P<0.001, n=313), lactate dehydrogenase (LDH; SMD =4.01, 95% CI: 3.79, 4.24, P<0.001, n=1,055), creatine kinase (CK; SMD =2.62, 95% CI: 2.2, 3.03, P<0.001, n=230;), CK-MB isoenzyme (CK-MB; SMD =3.07, 95% CI: 2.81, 3.34, P<0.001, n=600, activated partial thromboplastin time (APTT; SMD =0.63, 95% CI: 0.39, 0.87, P<0.001, n=351), and prothrombin time (P-T; SMD =1.83, 95% CI: 1.55, 2.11, P<0.001, n=351) were significantly higher than in patients with mild symptoms. On the contrary, lymphocyte count (SMD =-1.04, 95% CI: -1.21, -0.86, P<0.001, n=805) platelets (SMD =-1.47, 95% CI: -1.7, -1.24, P<0.001, n=653), monocyte count (SMD =-0.56, 95% CI: -0.8, -0.32, P<0.001, n=403), and albumin (SMD =-2.95, 95% CI: -3.21, -2.7, P<0.001, n=637) was significantly lower in patients with severe symptoms than in patients with mild symptoms. IL-6 (SMD =2.62, 95% CI: 2.15, 3.09, P<0.001, n=185), PCT (SMD =0.2, 95% CI: 0.16, 0.23, P<0.001, n=156), creatinine (SMD =2.29, 95% CI: 1.87, 2.7, P<0.001, n=213), and neutrophil counts (SMD =2.77, 95% CI: 2.38, 3.16, P<0.001, n=260) in patients with COVID-19 in the death group were significantly higher than that in patients in the survival group, while the lymphocyte count was significantly lower. Conclusions: In summary, current evidence show that those laboratory indicators are associated with the severity of COVID-19 and thus could be used as prognostic risk stratification of patients with COVID-19.

A systematic review on the application of vascular endothelial growth factors in preeclampsia.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is a disease associated with elevated blood pressure during pregnancy, accounting for 5-10% of all pregnancies, which includes: gestational hypertension, preeclampsia (PE), eclampsia, chronic hypertension with superimposed PE and chronic hypertension. PE is the most prevalent type of HDP that seriously threatens the life and health of mothers and infants. In-depth exploration of the pathogenesis can play an early role in predicting the disease. METHODS: A literature search was conducted in PubMed, Embase, Google Scholar, and other databases in the article. It was investigated by searching for literature published between 1993 and March 2021; the subject terms included-"vascular endothelial growth factor", "preeclampsia", and "pathogenesis". In the article, the inclusion criteria of literature should meet the definition of PE. It was excluded as reviews, case reports, narrative reviews, and publications that lack key information. RESULTS: Vascular endothelial growth factor (VEGF) family factor research provides pivotal value for early clinical prediction of PE. Soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) became a marker for early prediction of PE. Through the included 51 articles, the analysis of VEGF in PE and its pathway factors was summarized to clarify the pathogenesis further and provide innovative ideas for future research directions and clinical diagnosis. DISCUSSION: A systematic review of the VEGF family in the pathogenesis of PE was concluded in the study to find angiogenesis markers of PE from the pathogenesis of the available literature. Therefore, early intervention of clinical diseases could reduce maternal complications and ensure the maximum health of mothers and babies. There are differences in the research results of factors in the VEGF family, and further research is needed to provide accurate clinical evidence.

Knockdown of Mythimna separata chitinase genes via bacterial expression and oral delivery of RNAi effectors.

BACKGROUND: RNAi (RNA interference) is a technology for silencing of target genes via sequence-specific manner. RNAi technology has been used for development of anti-pathogenic crops. In 2007, development of transgenic plants resistant to insect herbivore using RNAi technology was first reported, leading to a burst of efforts aimed at exploitation of RNAi mechanism and control strategy against variety of insect species based on this technique. Mythimna separata belongs to noctuidae family of lepidoptera and is posing threat to crops of economic importance. Recently, outbreaks of M. separata severely threatens corn production in Northern China, calling for new control approaches. RESULTS: Chitinase genes were chosen as the target genes as they were expressed predominantly in the gut tissue and were reported to be ideal silencing targets in several insect species. Interfering sequences against the target genes were cloned into the L4440 vector to produce sequence specific dsRNAs (double-stranded RNAs). Recombinant L4440 vectors were transformed into Escherichia coli strain HT115 (DE3) which was defective in dsRNA degradation activity, so preserving the dsRNA from degradation by cellular machinery. The bacteria were mixed with artificial diet and were fed to M. separata. We showed that oral delivery of bacterially expressed dsRNA would lead to RNAi effects in the recipient insect. Quantitative real-time PCR results showed that expression level of target MseChi1 and MseChi2 genes in gut tissue of M. separata were down-regulated after oral delivery of engineered bacteria expressing the corresponding dsRNA. Sequence-specific siRNA (small interfering RNA) was detected in recipient insects, supporting the existence of siRNA-mediated silencing effects in M. separata. Furthermore, knockdown of MseChi1 and MseChi2 resulted in increased mortality and reduced body weight of the feeding larvae. CONCLUSION: We reported a simple and low cost experimental procedure to silence M. separata endogenous gene expression. Our research provides both an experimental foundation for using RNAi technology to control M. separata and also a useful research tool for loss-of-function study of important developmental and regulatory genes in this insect species.

Silencing of Target Chitinase Genes via Oral Delivery of dsRNA Caused Lethal Phenotypic Effects in Mythimna separata (Lepidoptera: Noctuidae).

Mythimna separata walker (Lepidoptera: Noctuidae) is a polyphagous, migratory corn pest. Outbreak of M. separata has led to severe damage to corn production recently in China. RNAi (RNA interference) is a gene silencing technology applied both in model and non-model organisms, and it is especially useful for the latter in which the reverse genetic research tools are not available. RNAi approach was broadly investigated in many plant pathogens and was used for the generation of anti-pest transgenic plants. We are proposing to use this technology to silence M. separata endogenous genes, thereby, providing a biocontrol method for this insect. Feeding of dsRNAs for target Chitinase genes resulted in substantial decreases of their transcript levels in M. separata. Furthermore, silencing of target Chitinase genes led to phenotypic effects such as reduced body weight and increased mortality. Our study provided both reverse genetic research tool and potential control strategy for this insect species.

Silencing of Mythimna separata chitinase genes via oral delivery of in planta-expressed RNAi effectors from a recombinant plant virus.

OBJECTIVES: To evaluate transient expression of RNA interference (RNAi) effectors in Nicotiana benthamiana plants by using recombinant virus vectors and also oral delivery of the effectors for silencing of Mythimna separata endogenous gene expression. RESULTS: Mythimna separata is a serious pest of corn production in China. To evaluate RNAi approaches to target specific RNAs in M. separate, we cloned fragments of the M. separata chitinase sequences into a virus vector in order to produce RNAi effectors during virus infection and replication in plants. When the infected plants were fed to M. separata, expression levels of target MseChi1 and MseChi2 genes were down-regulated by 76 and 45 %, respectively, and sequence-specific siRNAs were detected in recipient insects. RNAi-based silencing of chitinase genes also led to body weight decreases by 43 %. CONCLUSION: Our research demonstrates target mRNA knockdown and suggests a promising application for controlling of M. separata by in planta expression of RNAi effectors using a recombinant plant virus.