Network pharmacology-based analysis of heat clearing and detoxifying drug JC724 on the treatment of colorectal cancer

BACKGROUND Heat-clearing and detoxifying drugs has protective effect on colorectal cancer(CRC).Given the complicated features of Traditional Chinese medicine formulas,network pharmacology is an effective approach for studying the multiple interactions between drugs and diseases.AIM To systematically explore the anticancer mechanism of heat-clearing and detoxifying drug JC724.METHODS This study obtained the active compounds and their targets in JC724 from Traditional Chinese Medicine System Pharmacology Database.In addition,the CRC targets were obtained from Drugbank,TTD,DisGeNET and GeneCards databases.We performed transcriptome analysis of differentially expressed genes in CRC treated with JC724.Venn diagram was used to screen the JC724-CRC intersection targets as candidate targets.Core targets were selected by proteinprotein interaction network and herb ingredient-target-disease network analysis.The functional and pathway of core targets were analysed by enrichment analysis.RESULTS We found 174 active ingredients and 283 compound targets from JC724.940 CRC-related targets were reserved from the four databases and 304 CRC differentially expressed genes were obtained by transcriptome analysis.We constructed the network and found that the five core ingredients were quercetin,βBeta sitosterol,wogonin,kaempferol and baicalein.The core JC724-CRC targets were CYP1A1,HMOX1,CXCL8,NQO1 and FOSL1.JC724 acts on multiple signaling pathways associated with CRC,including the Nrf2 signaling pathway,oxidative stress,and the IL-17 signaling pathway.CONCLUSION In this study,we systematically analyzed the active ingredients,core targets and main mechanisms of JC724 in the treatment of CRC.This study could bring a new perspective to the heat-clearing and detoxifying therapy of CRC.

Extension Protocol for the Investigation on Nutrition Status and Clinical Outcome of Patients with Common Cancers in China(INSCOC)Study:2021 update

Background Malnutrition is common in patients with cancer,and this adversely affects the survival and quality of life of patients.Chinese Society for Nutritional Oncology issued a multi-center,large-scale,long-term follow-up prospective study,the Investigation on Nutrition Status and Clinical Outcome of Patients with Common Cancers in China(INSCOC study)since 2013.This is an extension to the previous 2013-2020 study protocol.This study still sought to:①address the prognostic impact of nutritional factors and quality of life on cancer patient survival;②describe the overall and cancer-specific incidence and/or distribution of malnutrition and different measurements of patient quality of life.Methods and study design This is an observational,multi-centered,hospital-based prospective cohort study.Data collection will be performed at baseline(within 48 hours after patient admission),during the hospital stay and 30 days after hospital admission.Follow-up will be conducted for 1-20 years after enrollment.The primary outcome will be the all-cause mortality/overall survival,and secondary outcomes will be the length of hospital stay and costs of hospitalization.Study factors will include demographic characteristics,tumor characteristics,information about chronic diseases,hematological measurements(e.g.,red blood cell count,total lymphocyte counts,hemoglobin,albumin,prealbumin,creatinine,C-reactive protein,IL-6),anthropometric measurements(e.g.,height,weight,arm circumference,arm muscle circumference,triceps skinfold thickness,and waist circumference),body composition parameters,PG-SGA scores,quality of life(as indicated by the QLQ-C30 questionnaire),muscle mass(as indicated by the calf circumference),muscle strength(as indicated by the handgrip strength),muscle function(as indicated by the six-meter walking speed test)and physical status assessments(as indicated by the Karnofsky Performance Status scores).This clinical study protocol was approved by local Ethics Committees of all the participating hospitals.Written informed consent is required for each subject included.Discussion This multi-center,large-scale,long-term follow up prospective study will help improve the diagnosis of malnutrition in cancer patients and identify the risk factors associated with adverse clinical outcomes.The anticipated results of this study will highlight the need for a truly scientific appraisal of nutrition therapy in Chinese oncology populations,and finally help treat the potentially reversible elements of malnutrition in cancer patients to improve their clinical outcomes in the future.

Hemolysis attributed to high dose vitamin C:Two case reports

BACKGROUND High-dose vitamin C treatment(HVCT)can reduce the adverse effect of chemotherapy and enhance the effect of antitumor therapy,which has been considered one of the safest alternative treatments.However,the severity of its adverse effects may have been underestimated.The most serious adverse effect is hemolysis,which may result in acute kidney injury or death.Although glucose-6-phosphate dehydrogenase(G6PD)deficiency is considered to be the main cause,the probability and pathological mechanism are not completely understood,leading to a lack of effective and standardized treatment methods.CASE SUMMARY Two patients with colorectal cancer developed hemolytic anemia after using 1 g/kg HVCT.In contrast to previous cases,the lowest hemoglobin level in the two cases was<50 g/L,which was lower than previously reported.This may be because Case 1 had chronic hepatitis B for many years,which caused abnormal liver reserve function,and Case 2 had grade II bone marrow suppression.Both patients improved and were discharged after blood replacement therapy.Our cases had the most severe degree of hemolysis but the best prognosis,suggesting that our treatment may be helpful for rescue of drug-induced hemolysis.This is the first review of the literature on hemolysis caused by HVCT,and we found that all patients with G6PD deficiency developed hemolysis after HVCT.CONCLUSION G6PD deficiency should be considered as a contraindication to HVCT,and it is not recommended for patients with bone marrow suppression,moderate-tosevere anemia,hematopoietic abnormalities,or abnormal liver and kidney function.Early blood purification and steroid therapy may avoid acute kidney injury or death caused by HVCT-related hemolytic anemia.

AIWW:a new nutrition-screening tool for the oncologic population

Malnutrition is a common comorbidity among patients with cancer.However,no nutrition-screening tool has been recognized in this population.A quick and easy screening tool for nutrition with high sensitivity and easy-to-use is needed.Based on the previous 25 nutrition-screening tools,the Delphi method was made by the members of the Chinese Society of Nutritional Oncology to choose the most useful item from each category.According to these results,we built a nutrition-screening tool named age,intake,weight,and walking(AIWW).Malnutrition was defined based on the scored patient-generated subjective global assessment(PG-SGA).Concurrent validity was evaluated using the Kendall tau coefficient and kappa consistency between the malnutrition risks of AIWW,nutritional risk screening 2002(NRS-2002),and malnutrition screening tool(MST).Clinical benefit was calculated by the decision curve analysis(DCA),integrated discrimination improvement(IDI),and continuous net reclassification improvement(c NRI).A total of 11,360 patients(male,n=6,024(53.0%)were included in the final study cohort,and 6,363 patients had malnutrition based on PG-SGA.Based on AIWW,NRS-2002,and MST,7,545,3,469,and1,840 patients were at risk of malnutrition,respectively.The sensitivities of AIWW,NRS-2002,and MST risks were 0.910,0.531,and 0.285,and the specificities were 0.768,0.946,and 0.975.The Kendall tau coefficients of AIWW,NRS-2002,and MST risks were 0.588,0.501,and 0.326,respectively.The area under the curve of AIWW,NRS-2002,and MST risks were0.785,0.739,and 0.630,respectively.The IDI,c NRI,and DCA showed that AIWW is non-inferior to NRS-2002(IDI:0.002(-0.009,0.013),c NRI:-0.015(-0.049,0.020)).AIWW scores can also predict the survival of patients with cancer.The missed diagnosis rates of AIWW,NRS-2002,and MST were 0.09%,49.0%,and 73.2%,respectively.AIWW showed a better nutritionscreening effect than NRS-2002 and MST for patients with cancer and could be recommended as an alternative nutritionscreening tool for this population.