| Objective:Screening of pulmonary nodules is essential to improve the survival rate of lung cancer.However,there is currently no other intervention except long-term imaging follow-up and non-surgical or surgical biopsy,which results in a waste of medical resources to a certain extent and increases the economic burden and psychological pressure of long-term interviewees.Professor Lin Hongsheng’s team has been committed to the prevention and treatment of malignant tumors for a long time.Now we summarize the prescription for the treatment of lung nodules by Professor Lin Hongsheng,explore its mechanism of action,and observe its clinical efficacy,in order to provide reference for the clinical treatment of lung nodules and the prevention and treatment of lung cancer.Methods1.Study 1:Professor Lin Hongsheng’s Prescription Mining for Differentiation and Treatment of Pulmonary NodulesMedical records of lung nodules patients in Professor Lin’s outpatient department who have been treated with TCM intervention for 6 months or more,whose nodules have been stable or reduced,and whose symptoms have been improved by TCM were collected.Effective prescription database was constructed.After the prescription drugs were organized,Aprior model was constructed to finally analyze the associated drug laws and explore the drug core network.2.Study 2:Molecular mechanism of central prescription action in pulmonary nodulesThe active ingredients and their action targets of core prescription drugs,as well as lung nodule related targets,are respectively searched through drug component databases such as TCMSP and disease databases such as Genecards.Using the common target of both drugs as a potential target for drugs to act on pulmonary nodules,construct a protein network,and calculate attribute values to screen out key targets.Use enrichment analysis to analyze and summarize the role of key targets,and ultimately further verify the main active ingredients and key targets through molecular docking.3.Study3:Preliminary study on the effect of core prescription on improving the symptoms of pulmonary nodules36 patients with pulmonary nodules who visited Director Lin Hongsheng’s outpatient Department from December 2022 to January 2023 were treated with core prescription for 1 month,and their symptoms,syndrome scores,anxiety scores,and related adverse reactions before and after medication were evaluated.SPSS 26.0 was used for data processing,and the scoring data were described by mean ± standard deviation,p<0.05 after T-test was considered statistically significant.Results1.Study 1:Professor Lin Hongsheng’s Prescription Mining for Differentiation and Treatment of Pulmonary Nodules(1)General data:152 patients were finally included,and males accounted for 24.34%of the sex;Women accounted for 75.66%.In terms of age,65.13%are 45-64 years old,10.53%are 18-44 years old,and 24.34%are over 65 years old.In terms of smoking history,92.1 1%of patients had no smoking history and 7.89%had smoking history.As for the family history of lung cancer,84.87%of patients had no family history of lung cancer,and 15.13%of patients had a family history of lung cancer.In terms of tumor history,24.07%of patients had no history of related tumors,and the remaining 75.93%had a history of malignant tumors,of which lung cancer accounted for the highest proportion,accounting for 56.17%.In terms of history of respiratory diseases,92.76%of patients did not have respiratory related diseases,and 0.66%,1.32%,1.32%,3.29%and 0.66%had previous history of emphysema,bronchial asthma,chronic obstructive pneumonia,chronic bronchitis and interstitial pneumonia,respectively.(2)Pulmonary nodules:A total of 43 nodules could be described in the chest CT reports provided by 36 patients within the past 1 month.The number of nodules ranged from 1 to multiple,and the multiple was unknown.The 43 describable pulmonary nodules were mainly distributed in the upper lobe of the right lung(30.23%),the lower lobe of the right lung,the middle lobe of the right lung,the upper lobe of the left lung,and the lower lobe of the left lung accounted for 18.60%,20.93%,13.95%,1 1.63%.respectively.The remaining 4.65%were not described in detail.The characteristics of pulmonary nodules were mainly ground glass nodules(44.19%),solid and partial solid accounted for 16.28%and 11.63%,respectively,and the other 27.91%did not describe the nodule characteristics in detail.In the patient,53.49%of pulmonary nodules were less than 6mm,32.56%were 8mm and above,6.89%were between 6 and 8mm.and 6.98%were not described in detail.(3)TCM tongue pulse and symptom type:A total of 280 prescriptions were entered.The tongue texture of patients was mainly red tongue(48.21%)and light red tongue(40.00%).White moss(92.86%)was the main coating on the tongue.The type of pulse were mainly deep and thready pulse(77.86%).The symptoms were mainly pulmonary qi deficiency(29.29%),qi-yin deficiency(25.64%)and pulmonary yin deficiency(16.07%).The symptoms were mainly qi deficiency(49.42%)and yin deficiency(33.50%).(4)Prescription data mining:280 prescriptions involving 118 traditional Chinese medicines.There are 22 Chinese medicines with a frequency of more than 80 times.Professor Lin’s medication was mainly supplementing deficiency medicine(32.22%),followed by antipyretic medicine(20.93%).The medicinal properties were mainly cold(2119 times),warm(1369 times),flat(1184 times).The medicinal flavors were mainly sweet(3194 times),bitter(2748 times),and spicy(1273 times).The main meridians are lung meridians(2261 times),liver meridians(2161 times),stomach meridians(1832 times),spleen meridians(1377 times),heart meridians(1384 times),and kidney meridians(1135 times).Commonly used medicinal pairs are Bran fried bighead atractylodes rhizome-Windbreak,Bran fried bighead atractylodes rhizomeAstragalus mongholicus,etc.Commonly used triangular drug combinations are Ophiopogon japonicus-Asparagus fern-Rhodiola,Windbreak-Bran fried bighead atractylodes rhizome-Astragalus mongholicus,etc.The final core network contains 18 Chinese medicines:Astragalus mongholicus,Ophiopogon japonicus,Bran fried bighead atractylodes rhizome,Bittersweet,windbreak,fingered citron,Asparagus fern.Fritillaria thunbergii,dandelion,Prognosticator,Hedyotis diffusa,Tuckahoe,Chinese trumpet creeper,nidus vespae,Caulis spatholobi,Buckwheat,White peony.2.Study 2:Molecular mechanism of central prescription action in pulmonary nodules(1)Drug active ingredients and target prediction:The core prescription contains 132 drug active ingredients and 599 related genes.According to the ranking of DC values,the main active ingredients were quercetin,β-sitosterol,stigmasterol.kaempferol,luteolin,etc.After constructing a pulmonary nodule active component target network diagram,1 32 active components and 599 target genes generated 73 1 nodes and 2955 edges.(2)Disease targets:2914 disease genes were obtained after screening,deduplication and merger.There are 275 targets in common with the 599 targets of the core prescription.(3)PPI network and core targets:After the PPI network was built,275 points and 6137 edges were obtained.After screening targets with DC value>67,68 core targets and 1896 edges were obtained.According to the DC score,the targets were successively ranked as AKT1,TNF,TP53,IL6,VEGFA,IL1B,JUN,EGFR.STAT3,CASP3,etc.(4)GO and KEGG analysis:Enrichment analysis involves 6785 biological processes,593 cellular components,1212 molecular functions,and 299 KEGG signaling pathways.The main biological processes include positive regulation of cell migration,response to hormones,regulation of cell adhesion,etc.;The main cellular components include membrane rafts,transcriptional regulatory complexes,extracellular matrices,etc.;Molecular functions include transcription factor binding,kinase binding,receptor ligand activity,etc.The KEGG signaling pathway is mainly cancer signaling pathway,human cytomegalovirus infection,glycoproteins,lipids and atherosclerosis in cancer.(5)Molecular docking and visualization:After molecular docking of quercetin,beta-sitosterol,kaempferol,stigmasterol and luteolin with five core targets of AKT1,TNF,IL6,TP53 and VEGFA,the docking scores were between-8.2 and-5.3.3.Study3:Preliminary study on the effect of core prescription on improving the symptoms of pulmonary nodules(1)General information:69.44%of the 36 patients were females.30.56%were males;13.89%were young adults,58.33%were middle-aged,and 27.78%were elderly;69.44%of patients had no family history of lung cancer,and 30.56%had a family history of lung cancer.83.33%of the patients had no smoking history,and 16.67%had a smoking history;50%of patients have a history of malignancy.(2)Pulmonary nodules:A total of 43 nodules can be described in the past 1 month,and the number of nodules was 1 to multiple,and the multiple details are unknown.The 43 described pulmonary nodules were mainly distributed in the upper lobe of the right lung(30.23%),the lower lobe of the right lung(18.60%),the middle lobe of the right lung(20.93%),the upper lobe of the left lung(13.95%),the lower lobe of the left lung(11.63%),and the remaining 4.65%were not described in detail.The characteristics of pulmonary nodules were mainly ground glass nodules(44.19%),solid and partial solid accounted for 16.28%and 11.63%,respectively,and the other 27.91%did not describe the nodule characteristics in detail.In the patient,53.49%of pulmonary nodules were less than 6mm,32.56%were 8mm and above,6.89%were between 6 and 8mm,and 6.98%were not described in detail.(3)Symptom and symptom scores:In the end,1 person fell off,and 35 people completed 1 month of traditional Chinese medicine intervention and symptom severity evaluation.As for symptom score,the total symptom score of patients was significantly decreased compared with that before medication(p<0.01).The scores of fatigue(p<0.01),less qi and lazy speech(p<0.01),dryness of mouth and throat(p<0.05),chest fullness tightness(p<0.05)and chest pain(p<0.05)were significantly reduced.In terms of syndrome scores,compared with before medication,Qi-deficiency(p<0.01)and Yin deficiency(p<0.05)syndrome scores were significantly decreased.(4)Anxiety score:Among the 35 patients who finally completed Chinese medicine for one month,62.86%did not have anxiety before medication,and the remaining 37.14%had different degrees of anxiety.After treatment,anxiety scores of 35 patients were all below 50 points,and significantly decreased compared with before treatment(p<0.01).(5)Adverse reactions:There were no adverse reactions during the patient’s medication.Conclusion1.Professor Lin believes that pulmonary nodules is asthenia in origin and superfluous in superficiality.The deficiency should be qi deficiency and yin deficiency,and the superfluous is mainly phlegm,stasis and poison.In terms of treatment,Professor Lin has implemented the concept of "solidifying the root and clearing the source",specifically,the solid root mainly regulates the formation of the microenvironment of nodules through the aspects of invigorating qi and nourishing yin,and Qingyuan removes pathological products such as stagnation,phlegm dampness,blood stasis,and turbidity by dissolving phlegm,regulating qi,activating blood and using anticancer drugs.Finally,the purpose of preventing pulmonary nodules from progressing is achieved.2.The core prescription may act on multiple targets to exert anti-tumor,anti-inflammatory,anti-viral,modulate immunity,regulate metabolism and other ways to act on lung nodules,and finally play the role of "solid roots and clean source"in preventing and treating malignant changes in lung nodules.3.It was preliminarily observed in this study that the symptoms of patients with pulmonary nodules were mainly concentrated in the aspects of qi deficiency and Yin deficiency,and the severity was mostly mild to moderate.Some patients with pulmonary nodules had mild anxiety.The core prescription of lung nodules has certain clinical effect on improving the symptoms related to Qi deficiency and Yin deficiency and psychological anxiety of patients with lung nodules. |
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