| ObjectiveBased on the mechanism of anti-oxidative stress,to explore the protective mechanism of fire needle therapy on nerve cells of CIPN.Preliminary exploration was carried out through animal experiments and verified in clinical research.At the same time,in the clinical study,to explore the effect of fire needle therapy on the clinical symptoms and quality of life of CIPN.This study is a cross study of oncology and acupuncture and moxibustion,which aims to enrich the subject content of oncology in traditional Chinese medicine.MethodsClinical Trials:(1)case sources:patients from the Cancer Center,Rehabilitation Center,Breast Department and Internal Medicine Department of the first affiliated Hospital of Guangzhou University of traditional Chinese Medicine from January 2020 to December 2021 were collected.A total of 70 cases were enrolled in this study,including 36 cases in the intervention group(basic treatment+fire needle)and 34 cases in the control group(basic treatment).(2)treatment:control group:oral mecobalamin tablets,500ug/tablets,one tablet each time,three times a day;intervention group:fire needle treatment,acupoints:Da zhui,Ming men,Yao yangguan,Ba xie,Ba feng.(3)observation indicators:general data of patients in the group were recorded before treatment,including name,age,sex and contact information;blood samples were collected before and 3 weeks after treatment for laboratory testing,and special observation indicators were:HIF-1a,caspase3.The quality of life was evaluated by telephone questionnaire before treatment,3 weeks after treatment and 3 weeks after treatment(6 weeks after treatment),including KPS score,QLQ-C30,QLQ-CIPN20 and NCICTCAE common adverse events.Animal experiment:(1)40 healthy male SD rats were randomly divided into 4 groups:Control group,Model group,FN group and Sham group,with 10 rats in each group.After adaptive feeding,the CIPN model was established,and the experimental rats were intraperitoneally injected with oxaliplatin at the dose of 4mg per kilogram,twice a week,on the 1st and 4th day of each week for 4 weeks.Pain behavior test was performed at 1 hour after administration.The von-frey filament was used for detection,and the 50%PWT of the experimental rat was calculated according to the up-down method.If the threshold decreased to less than 4G,the experimental rat model could be judged to be successful.(2)Experimental process:1.Grouping intervention:Control group:intraperitoneal injection of the same volume of 5%GS solution;Model group:intraperitoneal injection of oxaliplatin 4mg/kg;FN group:intraperitoneal injection of oxaliplatin 4mg/kg,fire needle treatment on the second day of injection;Sham group:intraperitoneal injection of oxaliplatin 4mg/kg,sham acupuncture treatment on the second day of injection,the number of times was the same as that of FN group.2.Selecting acupoints:Da zhui,Shen shu and Hou hui acupoints of rats were treated.3.Sampling and detection:on the 28th day of modeling,the rats were killed after behavioral examination,and the dorsal root ganglion and peripheral blood were taken.The change trend of 50%foot withdrawal threshold(PWT/g),mechanical pain hypersensitivity rate and hypersensitivity rate were evaluated by pain behavior index,and the protein and gene expression levels of HIF-1a,p53,NF-kB and caspase3 in DRG were detected by Western blotting(Western Blot)and real-time fluorescence quantitative(RT-qPCR).ResultsClinical Trials:In this clinical study,Lingnan fire needle therapy was compared with routine oral neurotrophic drugs,and scale evaluation and laboratory evaluation were used to evaluate the outcome.The evaluation of the scale selected the conventional KPS score,QLQ-C30 and QLQ-CIPN 20 scale.In addition to paying attention to the outcome of somatosensory function in patients with CIPN,we also paid attention to other clinical symptoms caused by chemotherapy,such as fatigue,nausea and vomiting,insomnia,diarrhea and so on.After treatment,there was significant difference in the intervention group compared with that before treatment(P<0.05),but there was no significant difference in the control group,and there was no significant difference between the two groups(P>0.05).During the follow-up,there were significant differences between the two groups compared with those before treatment,and the KPS scores of the tested patients were effectively improved.Although there was no statistical difference between the two groups after treatment,there was a trend of difference between the two groups.During the follow-up,there was a statistical difference between the two groups(P<0.05).Both of the two intervention methods could improve the KPS evaluation,but the intervention group improved more than the control group.QLQ-CIPN20 scale is a more effective and reliable scale specially developed for patients with CIPN.It has three subscales,including the evaluation of sensory,motor and autonomic function.There were significant differences between the two groups after treatment and during follow-up(P<0.05).The difference between the two groups was reflected in sensory function and overall function.After treatment and during follow-up,there was statistical significance between the two groups(P<0.05).It can be inferred that the treatment effect of the intervention group was better than that of the treatment group.QLQ-C30 is divided into three dimensions:functional score,symptom score and overall health evaluation.Fire needle therapy and neurotrophic drug therapy could improve the body,role,emotion,cognition and social function of patients with CIPN.The functional dimensions of the two groups were compared at each evaluation node,and there were only differences in physical function and total health evaluation(P<0.05).After 3 weeks of intervention,there was significant difference in body function between the two groups(P<0.05),and there was significant difference in total health status between the two groups(P<0.05).Among the 9 dimensions of evaluation of quality of life of cancer patients,there was no significant difference between the two groups at each node(P>0.05).In the dimensions of shortness of breath and diarrhea,there was no significant difference between the two groups before and after treatment(P>0.05).In the dimensions of fatigue,insomnia,constipation and economic difficulties,the two groups were followed up 3 weeks after intervention,which were significantly different from those before treatment(P<0.05),but there was significant statistical significance in the intervention group after treatment(P<0.05).In the dimension of loss of appetite,there was no difference between the two groups before and after treatment(P<0.05).After 3 weeks of intervention,there was significant difference in the intervention group compared with that before treatment(P<0.05).In the dimension of nausea and vomiting,there was no significant difference between the two groups after treatment(P>0.05).After 3 weeks of intervention,there was significant difference between the two groups(P<0.05).In the dimension of pain,there were significant differences in the intervention group after treatment and during follow-up compared with those before treatment(P<0.05),but there was no difference in the control group(P>0.05).Animal experiment:In this experiment,the animal model of CIPN was treated with fire needle intervention on D11.It was found that the body weight of rats in 1FN group could be increased after intervention,and the weight curve of rats injected with oxaliplatin was fitted.The body weight of rats in model group did not increase significantly,but some rats showed continuous weight loss.2 Fire has a certain therapeutic effect on CIPN,which can improve the neuropathic pain caused by CIPN and reduce the rate of hyperalgesia and hyperalgesia in the model.After administration of oxaliplatin in 3model,FN and sham,the expression of HIF-la in healthy rats increased significantly,while the expression of HIF-la in FN and sham decreased after intervention.One hour after injection,the pain behavior of experimental rats was detected,and the change trend of 50%pwt in rats was studied.after the third intraperitoneal injection of oxaliplatin in D8,the 50%pwt threshold of rats decreased to less than 4g,and the animal model of CIPN was established successfully.Fire needle intervention was performed 1 hour after injection of D11,and pain behavior test was performed 1 hour after intervention.From the behavioral results,it can be seen that both FN and sham have therapeutic effect on CIPN animal model,and the treatment of FN is statistically significant,which is more obvious than that of sham.After intervention,the 50%pwt threshold range of FN and sham showed an upward trend.After the successful modeling of D8,the 50%pwt threshold of control was significantly higher than that of model,FN and sham,and the threshold curve was separated.The 50%pwt threshold curve of FN increased at the beginning of D15,and the threshold curve of FN group was significantly higher than that of model and sham,respectively.FN appeared threshold curve separation from model and sham.Starting from D18,the 50%pwt threshold curve of sham increased,and there was significant difference between sham and model.The threshold curve of sham was separated from that of model.Von-Frey fiber 4G stimulated rat foot lifting reaction,which was a mechanical stimulation pain hypersensitivity reaction,and 15g stimulation rat foot lifting response,that is,mechanical stimulation hyperalgesia reaction.After intervention,the rate of pain hypersensitivity in FN group and sham group decreased,and the trend of FN was more obvious.After the successful establishment of D8,control was significantly higher than model,FN and sham,and the hypersensitivity curve was separated successfully.at the beginning of D11,the hypersensitivity curve of FN decreased,which was not significantly different from that of model and sham,but the hypersensitivity curve of D18FN decreased steadily,but there was no statistical difference compared with model and sham.After intervention,the rate of hyperalgesia in FN group and sham group decreased.After the successful establishment of D8,control was significantly higher than model,FN and sham,and the allergic reaction(rate)curve of FN reached the peak at D8 and decreased slowly until D25,which was statistically significant compared with model(P<0.05).After administration of oxaliplatin in model,FN and sham,the expression of HIF-1a in healthy rats increased significantly,while the expression of HIF-1a in FN and sham decreased after intervention.In addition,through the detection of NF-kB,p53 and caspase3 proteins,it was found that they changed in the same direction with HIF-1a,which maybe related to the expression of NF-kB and p53 induced by oxaliplatin and accelerated the apoptosis of nerve cells.Similarly,the expression of NF-kB and p53 in FN and sham decreased after intervention.ConclusionFire needle therapy has a certain therapeutic effect on CIPN,which can improve the neuropathic pain caused by CIPN and reduce the rate of hyperalgesia and hyperalgesia in the model.Through the detection of NFkB,p53 and caspase3 proteins,it was found that they changed in the same direction with HIF-1a,which may be related to the expression of NF-kB and p53 induced by oxaliplatin and accelerated the apoptosis of nerve cells.Similarly,the expression of NF-kB and p53 in FN and sham decreased after intervention.Lingnan fire needle therapy was compared with routine oral neurotrophic drugs,and scale evaluation and laboratory evaluation were used to evaluate the outcome.The evaluation of the scale selected the conventional KPS score,QLQ-C30 and QLQ-CIPN20 scale.In addition to paying attention to the outcome of somatosensory function in patients with CIPN,we also paid attention to other clinical symptoms caused by chemotherapy,such as fatigue,nausea and vomiting,insomnia,diarrhea and so on.Both of the two intervention methods can improve CIPN,and can improve the physical,role,emotional,cognitive and social functions of CIPN patients,but the intervention group has a greater degree of improvement than the control group.In the dimensions of shortness of breath and diarrhea,there was no difference between the two groups.Both groups can improve fatigue,insomnia,constipation,economic difficulties,loss of appetite,nausea and vomiting,and the intervention group has a better effect.In the pain dimension,the intervention group has outstanding performance,and the improvement effect is the most prominent. |
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