| Lung nodules are a common sign on CT screening,and with the continuous advancement and widespread use of modern medical technology,the detection rate of lung nodules is gradually increasing.With a 5-year survival rate of only 19%,lung cancer is the cancer with the greatest incidence and fatality rate in China.The high clinical difficulty in treating patients with advanced lung cancer has highlighted the importance of research into early lung cancer,especially lung nodules.How to predict the nature of lung nodules and diagnose lung cancer early so as to improve prognosis is therefore of great value.The theoretical system and rich clinical experience of TCM have provided new ideas and methods for the treatment of lung nodules.However,the TCM evidence of pulmonary nodules is diverse and complex,and there is a lack of objective studies to support this.A literature review and a clinical trial make up the two primary sections of this study.The review section firstly discusses the clinical management of pulmonary nodules in Chinese and Western medicine and the latest research progress;secondly,the physiological and pathological links between the lung and intestine from the perspective of the intestinal flora,and discusses the theoretical mechanism of "lung-gut correlation" in Chinese medicine.The clinical research part firstly investigates the distribution of different TCM syndromes among patients with pulmonary nodules by conducting a clinical questionnaire survey on their basic information,disease information related to pulmonary nodules and clinical symptoms,and summarises the most common TCM syndromes.Secondly,the clinical prognosis of patients with Yang deficiency pulmonary nodules was investigated in relation to the distribution of intestinal flora and T/B lymphocyte subsets based on the preliminary evidence survey.ObjectiveA combination of objective quantitative and qualitative studies was used to analyse and compare the distribution of TCM evidence patterns in patients with pulmonary nodules,and to explore the factors influencing pulmonary nodules from the perspective of intestinal flora and TB lymphocyte subsets.Research MethodA prospective observational clinical study was used to investigate the cross-section al clinical information of 177 patients with pulmonary nodules attending the wards and outpatient clinics of the Dongfang Hospital of Beijing University of Chinese Medicine between January 2021 and December 2021.General information(gender,age,weight and height,etc.),disease characteristics(nodule size,location,nature,etc.)and information on the four TCM consultations were collected to analyze the most widely distributed TCM evidence types in the lung nodule patient population.Data analysis was performed using SPSS26.0 statistical software.Based on the results of the preliminary evidence survey,biological samples(stool and peripheral blood)were collected from 54 patients with Yang deficiency type lung nodules who attended wards and outpatient clinics at the Dongfang Hospital of Beijing University of Chinese Medicine between January 2022 and December 2022.Two attending TCM oncologists independently judged and summarized a unified opinion on whether the enrolled patients were identified as Yang deficiency patients according to the Guidelines for Clinical Research on New Chinese Medicines.Other clinical information.Exploratory indicators included patients’ intestinal flora diversity and peripheral blood TB lymphocyte subpopulation,which were detected by 16srRNA method and flow cytometric analysis respectively.The intestinal flora biodiversity was analysed by the BioSignal analysis platform(http://cloud.majorbio.com)in subgroups of Yang deficiency patients with different nature of lung nodules and Yang deficiency lung cancer patients,and the TB lymphocyte subpopulation was used as an environmental factor for flora species and inter-sample correlation analysis.Results1.This study showed that the meanage of the patients with lung nodules partici pating in this evidence-based survey was 51.52±12.05 years,with the largest number of patients(66.10%)between the ages of 41 and 65 years;there was no statistically significant difference in the detection rate of lung nodules by gender.2.Among the TCM evidence types involved in the patients with lung nodules in this study,the single evidence type was most common in the general,Yang deficiency,Yin deficiency and Qi stagnation types;the Qi and Yin deficiency,Yang deficiency and Qi stagnation and Qi deficiency and Blood stasis types were most common in the group of patients with compound evidence types.3.In the study of the correlation between the nature of lung nodules and peripheral lymphocyte subsets,there was a statistically significant difference between patients with benign and malignant lung nodules in the absolute values of total lymphocytes and CD3+T cells(P=0.0097,P=0.0245).4.A total of 2427576 valid sequences were obtained for all valid samples,and 1050 OTUs were obtained by OTU species analysis.The alpha diversity of intestinal flora was slightly higher in patients with benign lung nodules than in patients with malignant lung nodules,but not statistically significant(P>0.05).Analysis by PCoA showed significant differences in the composition of the intestinal flora between the three groups studied.ANOSIM and Adonis similarity analysis suggested that the differences between the three groups were significantly greater than the differences within the groups,with high confidence(P=0.027).5.Analysis of the community composition showed a decreasing trend in the proportions of Faecalibacterium spp.in the patient communities of the LX,EX and Cancer groups at 15.01%,5.53%and 1.79%respectively,and a decreasing trend in the proportions of Bifidobacterium spp.at 11.66%,10.65%and 8.89%respectively.In contrast,the proportions of the Bacteroides,Blautia and Escherichia-Shigella spp.showed an increasing trend.The analysis of the differences in flora showed highly significant differences at the genus level between the three groups of patients for Faecalibacterium spp.,Agathobacter,Enterococcus,Lachnoclostridium and Lactobacillus spp.(P<0.05).The abundance of each community of the intestinal flora was generally higher in the LX group than in the EX group,with Lachnoclostridium and Enterococcus spp.being significantly more abundant in the EX group than in the LX group and the differenc es were statistically significant(P<0.001,P<0.05),while the abundance of Agathobact er spp.and Faecalibacterium spp.in the LX group was significantly higher than that in the EX group and the difference was statistically significant(P<0.05).6.The composition of intestinal flora in the three groups was significantly correlated with total lymphocytes(r2=0.2781 P=0.019),Th cells(r2=0.2781 P=0.019),TC cells(r2=0.2189 P=0.045),total B cells(r2=0.5443 P=0.001),total T cells(r2=0.3594 P=0.005)significant correlation and NK cells did not correlate with the structural distribution of the gut microbial community(P>0.05).Conclusion1.The most common TCM evidence types in patients with lung nodules are general,yang deficiency,yin deficiency and qi stagnation;2.Disorders in peripheral blood TB lymphocyte subsets in patients with poor prognosis of pulmonary nodules,with statistically significant differences in total lymphocyte count and total T lymphocyte count;3.Yang-deficient patients with benign lungnodules,patients with malignant lung nodules,and patients with lung cancer all have different intestinal flora compositions and distributions.As the prognosis of lung nodules worsened,the composition of the dominant flora changed dynamically,with a decreasing trend in the proportions of Faecalibacterium,Bifidobacterium,Subdoligranulum and Agathobacter spp.;and an increasing trend in the proportions of Bacteroides,Blautia and Escherichia-Shigella spp.There was also a correlation between human intestinal flora and TB lymphocyte subsets. |