OBJECTIVE:To investigate the efficacy of Longteng Tongluo recipe(龙藤通络方,LTTL)combined with threestep analgesia for the treatment of lung cancer pain,and the changes in serum miRNA expressions before-and after trea...OBJECTIVE:To investigate the efficacy of Longteng Tongluo recipe(龙藤通络方,LTTL)combined with threestep analgesia for the treatment of lung cancer pain,and the changes in serum miRNA expressions before-and after treatment with LTTL and its correlation with lung cancer pain.The possible mechanism underlying LTTL effects on the treatment of lung cancer pain was conducted.METHODS:The pilot study was conducted at the oncology ward of the Yueyang Hospital and the Longhua Hospital between March 2018 and October 2019.A prospective,single-blind,placebo controlled,randomized clinical trial of LTTL or placebo combined with three-step analgesia treatments were administered to 24 cancer pain patients diagnosed with lung cancer.Analgesic efficacy was investigated as the primary outcome.Equivalent morphine consumption and numerical rating scale(NRS)scores were used as the secondary outcome.In the present study,we utilized deep sequencing techniques to compare the differential miRNA expressions in serum samples obtained from two groups:the lung cancer pain treatment group(LTTL+three-step analgesia)and the control group(placebo+three-step analgesia).Next,we employed the target prediction database to investigate the target genes for differential miRNA expressions and Gene Ontology(GO)analysis along with Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to examine the roles and the major biochemical and signaling pathways related to the differentially expressed target genes,respectively.RESULTS:LTTL treatment significantly reduces the NRS score(P=0.021)as compared to those before treatment,along with significant reductions in the total morphine equivalent consumption(P=0.007)and the average daily equivalent morphine consumption(P=0.003)as opposed to the control group.The expressions of 31 miRNAs differed considerably between the two groups of patients(≥2 times up-modulated or down-regulated between these groups,P<0.05).For instance,the miRNAs expression levels for patients before treatment(has-miR-2110 and has-miR-7d-3p)were significantly enhanced as compared to the healthy people,after LTTL treatment,the expressions of miR-2110 and miR-7d-3p in patients with lung cancer pain reduced significantly.Studies show that the above two miRNAs were significantly associated with lung cancer pain,which could mediate lung cancer pain.Furthermore,we identified 355 genes as potential targets of the 31 differentially expressed miRNAs.Pathway enrichment analyses using KEGG and GO analysis indicated that these target genes may play a crucial role in the development and modulation of lung cancer pain.CONCLUSION:LTTL demonstrated a discernible impact on alleviating lung cancer pain and its mechanism of action may be related to the downregulation of has-miR-2110 and has-miR-7d-3p expressions.This pilot study provides support for further exploration of LTTL in patients with lung cancer pain.展开更多
基金a Special Clinical Research Initiative for the Health Business Sponsored by the Shanghai Municipal Health Commission:a Multicenter Randomized Controlled Clinical Study of Longteng Tongluo Recipe for the Treatment of Lung Cancer Pain(202040155)Xinglin Youth Talent Training System of Shanghai University of Traditional Chinese Medicine Xinglin Young Scholars:Study The Mechanism of Longteng Tongluo Recipe in Cancer Pain based on The Theory of Tonifying Yuan Qi and Detoxification(RC-2017-02-02)+2 种基金the Shanghai Municipal Science and Technology Commission's Special Biomedical Technology Support Plan:External Treatment of Cancer Pain of Traditional Chinese Medicine to Promote Percutaneous Absorption of Ultrasound Instrument(20S31904100)Science and Technology Commission of Shanghai Municipality:Shanghai Clinical Research Center of Traditional Chinese Medicine Oncology(21MC1930500)Science Foundation of Yueyang Hospital:Discussion on the Anti-apoptotic Effect of Qidongning Prescription on Lung Cancer Based on Energy Metabolismin Disorder of Mitochondria(2021yygq05)。
文摘OBJECTIVE:To investigate the efficacy of Longteng Tongluo recipe(龙藤通络方,LTTL)combined with threestep analgesia for the treatment of lung cancer pain,and the changes in serum miRNA expressions before-and after treatment with LTTL and its correlation with lung cancer pain.The possible mechanism underlying LTTL effects on the treatment of lung cancer pain was conducted.METHODS:The pilot study was conducted at the oncology ward of the Yueyang Hospital and the Longhua Hospital between March 2018 and October 2019.A prospective,single-blind,placebo controlled,randomized clinical trial of LTTL or placebo combined with three-step analgesia treatments were administered to 24 cancer pain patients diagnosed with lung cancer.Analgesic efficacy was investigated as the primary outcome.Equivalent morphine consumption and numerical rating scale(NRS)scores were used as the secondary outcome.In the present study,we utilized deep sequencing techniques to compare the differential miRNA expressions in serum samples obtained from two groups:the lung cancer pain treatment group(LTTL+three-step analgesia)and the control group(placebo+three-step analgesia).Next,we employed the target prediction database to investigate the target genes for differential miRNA expressions and Gene Ontology(GO)analysis along with Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to examine the roles and the major biochemical and signaling pathways related to the differentially expressed target genes,respectively.RESULTS:LTTL treatment significantly reduces the NRS score(P=0.021)as compared to those before treatment,along with significant reductions in the total morphine equivalent consumption(P=0.007)and the average daily equivalent morphine consumption(P=0.003)as opposed to the control group.The expressions of 31 miRNAs differed considerably between the two groups of patients(≥2 times up-modulated or down-regulated between these groups,P<0.05).For instance,the miRNAs expression levels for patients before treatment(has-miR-2110 and has-miR-7d-3p)were significantly enhanced as compared to the healthy people,after LTTL treatment,the expressions of miR-2110 and miR-7d-3p in patients with lung cancer pain reduced significantly.Studies show that the above two miRNAs were significantly associated with lung cancer pain,which could mediate lung cancer pain.Furthermore,we identified 355 genes as potential targets of the 31 differentially expressed miRNAs.Pathway enrichment analyses using KEGG and GO analysis indicated that these target genes may play a crucial role in the development and modulation of lung cancer pain.CONCLUSION:LTTL demonstrated a discernible impact on alleviating lung cancer pain and its mechanism of action may be related to the downregulation of has-miR-2110 and has-miR-7d-3p expressions.This pilot study provides support for further exploration of LTTL in patients with lung cancer pain.
