Deciphering the potential mechanism of Radix Rehmanniae Praeparata for treating cancer-related anemia based on network pharmacology and molecular docking technology

Background:Rehmanniae Radix Praeparata(RRP,Shu Dihuang in Cinese)is a traditional Chinese herb with multiple pharmacological effects and is commonly used to treat blood deficiency syndrome,such as cancer-related anemia(CRA),alone or in combination with other herbs.However,its main active ingredients and mechanisms of action in treating CRA remain unknown.This study aims to elucidate RRP’s potential mechanism and main active components in treating CRA by using network pharmacology and molecular docking technology system.Methods:The main components of RRP were obtained by the TCMSP database and literature search,and active components and potential targets were obtained by the SwissADME and SwissTargetPridiction databases.CRA targets were collected through GeneCards,DisGeNET,and DrugBank databases.Protein-protein interaction networks of potential targets were constructed via STRING 11.5 and analyzed visually with Cytoscape 3.9.1.The Metascape platform was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis,which were subsequently visualized with Cytoscape 3.9.1 or SangerBox platform.Moreover,Autodock Vina was used for the molecular docking of potential targets and main active ingredients that were visualized with PyMOL software.Results:In this study,31 main active ingredients of PPR were screened,and 155 related targets related to CRA were unearthed.Protein-protein interaction results showed that PPR’s core proteins for CRA intervention correlate to STAT3,SRC,MAPK3,MAPK1,PIK3R1,PIK3CA,and AKT.Multiple signaling pathways were closely related to the treatment of CRA intervened by PPR,including the PI3K-Akt signaling pathway,HIF-1 signaling pathway,JAK-STAT3 signaling pathway,TNF-αsignaling,cytokine signaling pathway and NF-kappB signaling pathway,which are closely involved in the proliferation and differentiation of hematopoietic stem cell and inflammatory response.Molecular docking results showed that these potential targets had good conformation with the core active components of RRP for treating CRA.Conclusion:This study revealed RRP’s main active components and potential molecular mechanisms in treating CRA,providing a reference for subsequent basic research.

Efficacy of probiotics or synbiotics for critically ill adult patients:a systematic review and meta-analysis of randomized controlled trials

Background:Microbial dysbiosis in critically ill patients is a leading cause of mortality and septic complications.Probiotics and synbiotics have emerged as novel therapy on gut microbiota to prevent septic complications.However,current evidence on their effects is conflicting.This work aims to systematically review the impact of probiotics or synbiotics in critically ill adult patients.Methods:A comprehensive search of the PubMed,CBM,Embase,CENTRAL,ISI,and CNKI databases was performed to identify randomized controlled trials that evaluate probiotics or synbiotics in critically ill patients.The quality assessment was based on the modified Jadad’s score scale and the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1.The major outcome measure was mortality.Secondary outcomes included incidence of septic complications,sepsis incidence,length of intensive care unit(ICU)stay,incidence of non-septic complication,and ventilator day.Data synthesis was conduct by Review Manager 5.4.Results:A total of 25 randomized controlled trials reporting on 5049 critically ill patients were included.In the intervention group,2520 participants received probiotics or synbiotics,whereas 2529 participants received standard care or placebo.Pooling data from randomized controlled trials demonstrated a significant reduction in the incidence of ventilator-associated pneumonia(VAP)in the treatment group[(risk ratio(RR)0.86;95%confidence interval(CI):0.78-0.95;p<0.003,I^(2)=85%)].However,in the subgroup analysis,the reduction of incidence of VAP was only significant in patients receiving synbiotics(RR=0.61,95%CI:0.47-0.80,p=0.0004,I^(2)=40%)and not significant in those receiving only probiotics(RR=0.91,95%CI:0.82-1.01,p=0.07,I^(2)=65%).Moreover,sepsis incidence of critically ill patients was only significantly reduced by the addition of synbiotics(RR=0.41;95%CI:0.22-0.72,p=0.005,I^(2)=0%).The incidence of ICU-acquired infections was significantly reduced by the synbiotics therapy(RR=0.72;95%CI:0.58-0.89,p=0.0007,I^(2)=79%).There was no significant difference in mortality,diarrhea,or length of ICU stay between the treatment and control groups.Conclusions:Synbiotics is an effective and safe nutrition therapy in reducing septic complications in critically ill patients.However,in such patients,administration of probiotics alone compared with placebo resulted in no difference in the septic complications.

Gut,metabolism and nutritional Support for COVID-19:Experiences from China

There is little research that focuses on the relationship between the gut,metabolism,nutritional support and COVID-19.As a group of Chinese physicians,nutritionists and scientists working on the frontline treating COVID-19 patients,we aim to integrate our experiences and the current clinical evidence to address this pressing issue in this article.Based on our clinical observations and available evidence,we recommend the following practice.Firstly,the Nutritional Risk Screening 2002 tool should be used routinely and periodically;for patients with a score≥3,oral nutritional supplements should be given immediately.Secondly,for patients receiving the antiviral agents lopinavir/ritonavir,gastrointestinal side effects should be monitored for and timely intervention provided.Thirdly,for feeding,the enteral route should be the first choice.In patients undergoing mechanical ventilation,establishing a jejunal route as early as possible can guarantee the feeding target being achieved if gastric dilatation occurs.Fourthly,we suggest a permissive underfeeding strategy for severe/critical patients admitted to the intensive care unit during the first week of admission,with the energy target no more than 20 kcal/kg/day(for those on mechanical ventilation,this target may be lowered to 10–15 kcal/kg/day)and the protein target around 1.0–1.2 g/kg/day.If the inflammatory condition is significantly alleviated,the energy target may be gradually increased to 25–30 kcal/kg/day and the protein target to 1.2–1.5 g/kg/day.Fifthly,supplemental parenteral nutrition should be used with caution.Lastly,omega-3 fatty acids may be used as immunoregulators,intravenous administration of omega-3 fatty emulsion(10 g/day)at an early stage may help to reduce the inflammatory reaction.