Study on the correlation between the distribution of Traditional Chinese Medicine syndrome elements and salivary microbiota in patients with pulmonary nodules_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

XIANG Hongxia ¹ , HE Jiawei ¹ , TAN Shiyan ¹ , YOU Ting ³ , FU Xi ^1,2 , YOU Fengming ^1,2 , SHI Wei ⁴ ,  MA Qiong ¹ ,  REN Yifeng ^1,2

1. Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, P. R. China;
2. TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, P. R. China;
3. Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;
4. Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;

Corresponding author：

MA Qiong, Email: ryftcm.dr@yahoo.com; REN Yifeng, Email: Maqiong.Dr@outlook.com

Keywords：

Psulmonary nodules; high-throughput 16S rRNA sequencing; Traditional Chinese Medicine (TCM) syndrome elements; salivary microbiota

DOI：

10.7507/1007-4848.202406034

Video：

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Objective This study aimed to analyze the differences between the distribution of Traditional Chinese Medicine (TCM) syndrome elements and salivary microbiota between the individuals with pulmonary nodules and those without. Additionally, it seeked to explore the potential correlation between the distribution of Traditional Chinese Medicine (TCM) syndrome elements and salivary microbiota in patients with pulmonary nodules. Methods We retrospectively recruited 173 patients with pulmonary nodules (PN) and 40 healthy controls (HC). The four diagnostic information was collected from all participants, and syndrome differentiation method was used to analyze the distribution of Traditional Chinese Medicine (TCM) syndrome elements in both groups. Saliva samples were obtained from the subjects for 16S rRNA high-throughput sequencing to obtain differential microbiota and to explore the correlation between Traditional Chinese Medicine (TCM) syndrome elements and salivary microbiota in the evolution of the pulmonary nodule disease. Results The study found that in the PN group, the primary Traditional Chinese Medicine (TCM) syndrome elements related to disease location were the lung and liver, and the primary Traditional Chinese Medicine (TCM) syndrome elements related to disease nature were yin deficiency and phlegm. In the HC group, the primary Traditional Chinese Medicine (TCM) syndrome elements related to disease location were the lung and spleen, and the primary Traditional Chinese Medicine (TCM) syndrome elements related to disease nature were dampness and qi deficiency. There were differences between the two groups in the distribution of Traditional Chinese Medicine (TCM) syndrome elements related to disease location (lung, liver, kidney, exterior, heart) and disease nature (yin deficiency, phlegm, qi stagnation, qi deficiency, dampness, blood deficiency, heat, blood stasis) (P<0.05). The species abundance of the salivary microbiota was higher in the PN group than that in the HC group (P<0.05), and there were significant differences in community composition between the two groups (P<0.05). Correlation analysis using multiple methods, including Mantel test network heatmap analysis and Spearman correlation analysis and so on, showed that in the PN group, Prevotella and Porphyromonas were positively correlated with disease location in the lung, and Porphyromonas and Granulicatella were positively correlated with disease nature in yin deficiency (P<0.05). Conclusion The study concludes that there are notable differences in the distribution of Traditional Chinese Medicine (TCM) syndrome elements and the species abundance and composition of salivary microbiota between patients with pulmonary nodules and healthy individuals. The distinct external syndrome manifestations in patients with pulmonary nodules, compared to healthy individuals, may be a cascade event triggered by changes in the salivary microbiota. The dual correlation of Porphyromonas with both disease location and nature suggests that changes in its abundance may serve as an objective indicator for the improvement of symptoms in patients with yin deficiency-type pulmonary nodules.

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2.	Kim YW, Kang HR, Kwon BS, et al. Low-dose chest computed tomographic screening and invasive diagnosis of pulmonary nodules for lung cancer in never-smokers. Eur Respir J, 2020, 56(5): 2000177.
3.	Wu Z, Wang F, Cao W, et al. Lung cancer risk prediction models based on pulmonary nodules: A systematic review. Thorac Cancer, 2022, 13(5): 664-677.
4.	Liu YB, Zhang XM, Jiang LD, et al. Clinical obser'vation on the methods of benefiting lung, promoting blood circulation, eliminating phlegm anddispersing stagnation in treating 187 cases of pulmonary nodules. Chin J Trad Chin Med Pharm, 2020, 35(2): 992-994.
5.	Yu MW, Zhang HR, Zhang XH, et al. Expert consensus on clinical diseases responding specifically to Traditional Chinese Medicine pulmonary nodules. Chin J Experiment Trad Med Form, 2024, 30(6): 238-245.
6.	Li X, Liu S, Wang XQ, et al. Advantages and considerations of Traditional Chinese Medicine in preventing and treating pulmonary nodules, J Bas Chin Med, 2023, 29(11): 1814-1817.
7.	Yang GW, Zhang XH, Zhang HR, et al. Expert consensus on whole-process management of pulmonary nodules with integrated Traditional Chinese Medicine and western medicine. Chin Jf Experiment Trad Med Form, 2024, 30(1): 149-159.
8.	Mochizuki T, I kari K, Yano K, et al. Five-year incidence of common comorbidities, such as hypertension, dyslipidemia, diabetes mellitus, cardiovascular disease, cerebrovascular disease and cancer, in older Japanese patients with rheumatoid arthritis. Geriatr Gerontol Int, 2019, 19(7): 577-581.
9.	Li KX, Study on the Distribution of Syndromes and Syndrome Elements of Chronic Gastritis and Their Correlation with Cold-Heat Syndromes and Tongue Coating Microbiota. Beijing: Beiing University of Chinese Medicine, 2021.
10.	Toumazis I, Bastani M, Han SS, et al. Risk-based lung cancer screening: A systematic review. Lung Cancer, 2020, 147: 154-186.
11.	Tuganbaev T, Yoshida K, Honda K. The effects of oral microbiota on health. Science, 2022, 376(6596): 934-936.
12.	Natalini JG, Singh S, Segal LN. The dynamic lung microbiome in health and disease. Nat Rev Microbiol, 2023, 21(4): 222-235.
13.	Li R, Li J, Zhou X. Lung microbiome: New insights into the pathogenesis of respiratory diseases. Signal Transduct Target Ther, 2024, 9(1): 19.
14.	Ren YF, Ma Q, Zeng X, et al. Saliva-microbiome-derived signatures: Expected to become a potential biomarker for pulmonary nodules (MCEPN-1). BMC Microbiol, 2024, 24(1): 132.
15.	Li MZ, Chen QL, Chen QF, et al. Exploration on the significance of TCM syndrome differentiation in micro index from syndrome elements differentiation principle, Chin J Trad Chin Med Pharm, 2021, 36(11): 6285-6288.
16.	Huang YY, Lin XJ, Li XH, et al. Study on the correlation between the distribution of traditional Chinese medicine syndrome elements and intestinal flora in different atrophic areas of chronic atrophic gastritis. China Journal of Traditional Chin Med Pharm, 2024, 39(1): 435-439.
17.	Shen R, Li MF, Peng YH, et al. Study on the correlation between the formation of spleen-stomach deficiency syndromeand tongue coating microbiota in patients with gastric cancer. J Nanjing University Trad Chin Med, 2020, 36(2): 221-228.
18.	Zhang X, Bai L, Jin F, et al. Interpretation of chinese expert consensus on the diagnosis and treatment of pulmonary nodules(2018 version). Chin J Tuber Resp Dis, 2018, 41(10): 763-771.
19.	Zhu WF. Fundamentals of Traditional Chinese Medicine diagnosis and differential diagnosis. Beijing: People's Medical Publishing House, 2008. 88-90.
20.	Jiang PY. Study on the distribution characteristics of Traditional Chinese Medicine Syndromes in pulmonary nodules. Beijing: Beijing University of Chinese Medicine, 2021.
21.	Zhou J, Wang YH, Li ZM, et al. Discussion on the pathogenesis of pulmonary nodules "deficiency of lung qi and obstruction of lung collaterals by toxin" under the guidance of collateral disease theory. China Medical Herald, 2020, 17(28): 133-136.
22.	Huang J, Huang J. Microbial biomarkers for lung cancer: current understandings and limitations. J Clin Med, 2022, 11(24): 7298.
23.	Liu S, Zhou X, Peng X, et al. Porphyromonas gingivalis promotes immunoevasion of oral cancer by protecting cancer from macrophage attack. J Immunol, 2020, 205(1): 282-289.
24.	Shi J, Yang Y, Xie H, et al. Association of oral microbiota with lung cancer risk in a low-income population in the Southeastern USA. Cancer Causes Control, 2021, 32: 1423-1432.
25.	Vogtmann E, Hua X, Yu G, et al. The oral microbiome and lung cancer risk: An analysis of 3 prospective cohort studies. JNCI-J Natl Cancer Inst, 2022, 114: 1501-1510.
26.	Zeng W, Zhao C, Yu M, et al. Alterations of lung microbiota in patients with non-small cell lung cancer. Bioengineered, 2022, 13(3): 6665-6677.
27.	Chen Y, Zhou R, Yi Z, et al. Porphyromonas gingivalis induced inflammatory responses and promoted apoptosis in lung epithelial cells infected with H1N1 via the Bcl-2/Bax/Caspase-3 signaling pathway. Mol Med Rep, 2018, 18: 97-104.
28.	Chen Y. The tongue coaling microbiome in lung cancer patients as revealed by nex-generaion sequencing. Wuhu: Wannan Medical college, 2016.
29.	Yan X, Yang M, Liu J, et al. Discovery and validation of potential bacterial biomarkers for lung cancer. Am J Cancer Res, 2015, 5(10): 3111-3122.
30.	Hosgood HD, Sapkota AR, Rothman N, et al. The potential role of lung microbiota in lung cancer attributed to household coal burning exposures. Environ Mol Mutagen, 2014, 55(8): 643-651.
31.	Tuominen H, Rautava J. Oral Microbiota and Cancer Development. Pathobiology, 2021, 88(2): 116-126.
32.	Shi T, Wang J, Dong J, et al. Periodontopathogens Porphyromonas gingivalis and fusobacterium nucleatum and their roles in the progression of respiratory diseases. Pathogens, 2023, 12(9): 1110.
33.	Liu S, Zhou X, Peng X, et al. Porphyromonas gingivalis promotes immunoevasion of oral cancer by protecting cancer from macrophage attack. J Immunol, 2020, 205(1): 282-289.
34.	Jinas DE, Reuland DS, Reddy SM, et al. Screening for lung cancer with low-dose computed tomography: updated evidence report and systematic review for the US preventive services task force. Jama, 2021, 325(10): 971-987.
35.	Lovly CM. Expanding horizons for treatment of early-stage lung cancer. N Engl J Med, 2022, 386(21): 2050-2051.
36.	Oyunbileg B. Comparative Study of Syndrome Differentiation and Tongue Coating Microbiota in Patients with Chronic Atrophic Gastritis in China and Mongolia. Beijing: Beijing University of Chinese Medicine, 2022.
37.	Shan XJ, Sun ZY, Zhou P, et al. Study on disease-syndrome distribution law of intestinal flora lmbalance based on literature review. J Bas Chin Med, 2022, 28(4): 571-574+662.
38.	Zhang K. The Traditional Chinese Medicine expression of defensive Qi and immune cells. Hubei J Trad Chin Med, 2001, 23(3): 3-4.
39.	Wen C, Zheng Z, Shao T, et al. Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis. Genome Biol, 2017, 18(1): 142.
40.	Chopra A, Shiheido-Watanabe Y, Eberhard J. Editorial: Porphyromonas gingivalis: molecular mechanisms of invasion, immune evasion, and dysbiosis. Front Cell Infect Microbiol, 2023, 13: 1289103.
41.	Liu YW, Yuan X, Sun W, et al. Clinical significance and prognostic value of Porphyromonas gingivalis infection in lung cancer. J Jinan University(Natural Science & Medicine Edition), 2020, 41(3): 260-267.
42.	Zhao Y, Ye Q, Feng Y, et al. Prevotella genus and its related NOD-like receptor signaling pathway in young males with stage Ⅲ periodontitis. Front Microbiol, 2022, 13: 1049525.
43.	Zhang JH, Chen YC, Xu N, et al. Interpretation of the mechanism of Yu's Herbal Tea in the treatment of inflammation based on network pharmacology and molecular dockin. Special Wild Economic Animal and Plant Research, 2024, 46(01): 62-71.
44.	Hong BY, Sobue T, Choquette L, et al. Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis. Microbiome, 2019, 7(1): 66.
45.	Eriksson K, Lundmark A, Delgado LF, et al. Salivary microbiota and host-inflammatory Responses in periodontitis affected individuals with and without rheumatoid arthritis. Front Cell Infect Microbiol, 2022, 12: 841139.
46.	Scanu M, Toto F, Petito V, et al. An integrative multi-omic analysis defines gut microbiota, mycobiota, and metabolic fingerprints in ulcerative colitis patients. Front Cell Infect Microbiol, 2024, 14: 1366192.
47.	Bhardwaj RG, Al-Khabbaz A, Karched M. Cytokine induction of peripheral blood mononuclear cells by biofilms and biofilm supernatants of Granulicatella and Abiotrophia spp. Microb Pathog, 2018, 114: 90-94.
48.	Irfan M, Delgado ZR, Frias-lopez J. The Oral Microbiome and Cancer. Front Immunol, 2020, 11: 591088.
49.	Watanabe N, Yokoe S, Ogata Y, et al. Exposure to Porphyromonas gingivalis induces production of proinflammatory cytokine via TLR2 from human respiratory epithelial cells. J Clin Med, 2020, 9(11): 3433.
50.	Liu YT, Li M, Ma ZP. Treatment of the inflammatory microenyironment of pulmonary nodules from phlegm. J Changchun University Chin Med, 2020, 36(4): 620-623.

1. Chinese Medical Education Association Lung Cancer Medical Education Committee, China Lung Cancer Coalition in Thoracic Surgery, Chinese Anti-Cancer Association Tumor Ablation Therapy Professional Committee, et al. Chinese Expert Consensus on Multidisciplinary Diagnosis and Treatment of Multiple Ground-Glass Nodular Lung Cancer (2024 version). Chin J Intern Med, 2024, 63(2): 153-169.
2. Kim YW, Kang HR, Kwon BS, et al. Low-dose chest computed tomographic screening and invasive diagnosis of pulmonary nodules for lung cancer in never-smokers. Eur Respir J, 2020, 56(5): 2000177.
3. Wu Z, Wang F, Cao W, et al. Lung cancer risk prediction models based on pulmonary nodules: A systematic review. Thorac Cancer, 2022, 13(5): 664-677.
4. Liu YB, Zhang XM, Jiang LD, et al. Clinical obser'vation on the methods of benefiting lung, promoting blood circulation, eliminating phlegm anddispersing stagnation in treating 187 cases of pulmonary nodules. Chin J Trad Chin Med Pharm, 2020, 35(2): 992-994.
5. Yu MW, Zhang HR, Zhang XH, et al. Expert consensus on clinical diseases responding specifically to Traditional Chinese Medicine pulmonary nodules. Chin J Experiment Trad Med Form, 2024, 30(6): 238-245.
6. Li X, Liu S, Wang XQ, et al. Advantages and considerations of Traditional Chinese Medicine in preventing and treating pulmonary nodules, J Bas Chin Med, 2023, 29(11): 1814-1817.
7. Yang GW, Zhang XH, Zhang HR, et al. Expert consensus on whole-process management of pulmonary nodules with integrated Traditional Chinese Medicine and western medicine. Chin Jf Experiment Trad Med Form, 2024, 30(1): 149-159.
8. Mochizuki T, I kari K, Yano K, et al. Five-year incidence of common comorbidities, such as hypertension, dyslipidemia, diabetes mellitus, cardiovascular disease, cerebrovascular disease and cancer, in older Japanese patients with rheumatoid arthritis. Geriatr Gerontol Int, 2019, 19(7): 577-581.
9. Li KX, Study on the Distribution of Syndromes and Syndrome Elements of Chronic Gastritis and Their Correlation with Cold-Heat Syndromes and Tongue Coating Microbiota. Beijing: Beiing University of Chinese Medicine, 2021.
10. Toumazis I, Bastani M, Han SS, et al. Risk-based lung cancer screening: A systematic review. Lung Cancer, 2020, 147: 154-186.
11. Tuganbaev T, Yoshida K, Honda K. The effects of oral microbiota on health. Science, 2022, 376(6596): 934-936.
12. Natalini JG, Singh S, Segal LN. The dynamic lung microbiome in health and disease. Nat Rev Microbiol, 2023, 21(4): 222-235.
13. Li R, Li J, Zhou X. Lung microbiome: New insights into the pathogenesis of respiratory diseases. Signal Transduct Target Ther, 2024, 9(1): 19.
14. Ren YF, Ma Q, Zeng X, et al. Saliva-microbiome-derived signatures: Expected to become a potential biomarker for pulmonary nodules (MCEPN-1). BMC Microbiol, 2024, 24(1): 132.
15. Li MZ, Chen QL, Chen QF, et al. Exploration on the significance of TCM syndrome differentiation in micro index from syndrome elements differentiation principle, Chin J Trad Chin Med Pharm, 2021, 36(11): 6285-6288.
16. Huang YY, Lin XJ, Li XH, et al. Study on the correlation between the distribution of traditional Chinese medicine syndrome elements and intestinal flora in different atrophic areas of chronic atrophic gastritis. China Journal of Traditional Chin Med Pharm, 2024, 39(1): 435-439.
17. Shen R, Li MF, Peng YH, et al. Study on the correlation between the formation of spleen-stomach deficiency syndromeand tongue coating microbiota in patients with gastric cancer. J Nanjing University Trad Chin Med, 2020, 36(2): 221-228.
18. Zhang X, Bai L, Jin F, et al. Interpretation of chinese expert consensus on the diagnosis and treatment of pulmonary nodules(2018 version). Chin J Tuber Resp Dis, 2018, 41(10): 763-771.
19. Zhu WF. Fundamentals of Traditional Chinese Medicine diagnosis and differential diagnosis. Beijing: People's Medical Publishing House, 2008. 88-90.
20. Jiang PY. Study on the distribution characteristics of Traditional Chinese Medicine Syndromes in pulmonary nodules. Beijing: Beijing University of Chinese Medicine, 2021.
21. Zhou J, Wang YH, Li ZM, et al. Discussion on the pathogenesis of pulmonary nodules "deficiency of lung qi and obstruction of lung collaterals by toxin" under the guidance of collateral disease theory. China Medical Herald, 2020, 17(28): 133-136.
22. Huang J, Huang J. Microbial biomarkers for lung cancer: current understandings and limitations. J Clin Med, 2022, 11(24): 7298.
23. Liu S, Zhou X, Peng X, et al. Porphyromonas gingivalis promotes immunoevasion of oral cancer by protecting cancer from macrophage attack. J Immunol, 2020, 205(1): 282-289.
24. Shi J, Yang Y, Xie H, et al. Association of oral microbiota with lung cancer risk in a low-income population in the Southeastern USA. Cancer Causes Control, 2021, 32: 1423-1432.
25. Vogtmann E, Hua X, Yu G, et al. The oral microbiome and lung cancer risk: An analysis of 3 prospective cohort studies. JNCI-J Natl Cancer Inst, 2022, 114: 1501-1510.
26. Zeng W, Zhao C, Yu M, et al. Alterations of lung microbiota in patients with non-small cell lung cancer. Bioengineered, 2022, 13(3): 6665-6677.
27. Chen Y, Zhou R, Yi Z, et al. Porphyromonas gingivalis induced inflammatory responses and promoted apoptosis in lung epithelial cells infected with H1N1 via the Bcl-2/Bax/Caspase-3 signaling pathway. Mol Med Rep, 2018, 18: 97-104.
28. Chen Y. The tongue coaling microbiome in lung cancer patients as revealed by nex-generaion sequencing. Wuhu: Wannan Medical college, 2016.
29. Yan X, Yang M, Liu J, et al. Discovery and validation of potential bacterial biomarkers for lung cancer. Am J Cancer Res, 2015, 5(10): 3111-3122.
30. Hosgood HD, Sapkota AR, Rothman N, et al. The potential role of lung microbiota in lung cancer attributed to household coal burning exposures. Environ Mol Mutagen, 2014, 55(8): 643-651.
31. Tuominen H, Rautava J. Oral Microbiota and Cancer Development. Pathobiology, 2021, 88(2): 116-126.
32. Shi T, Wang J, Dong J, et al. Periodontopathogens Porphyromonas gingivalis and fusobacterium nucleatum and their roles in the progression of respiratory diseases. Pathogens, 2023, 12(9): 1110.
33. Liu S, Zhou X, Peng X, et al. Porphyromonas gingivalis promotes immunoevasion of oral cancer by protecting cancer from macrophage attack. J Immunol, 2020, 205(1): 282-289.
34. Jinas DE, Reuland DS, Reddy SM, et al. Screening for lung cancer with low-dose computed tomography: updated evidence report and systematic review for the US preventive services task force. Jama, 2021, 325(10): 971-987.
35. Lovly CM. Expanding horizons for treatment of early-stage lung cancer. N Engl J Med, 2022, 386(21): 2050-2051.
36. Oyunbileg B. Comparative Study of Syndrome Differentiation and Tongue Coating Microbiota in Patients with Chronic Atrophic Gastritis in China and Mongolia. Beijing: Beijing University of Chinese Medicine, 2022.
37. Shan XJ, Sun ZY, Zhou P, et al. Study on disease-syndrome distribution law of intestinal flora lmbalance based on literature review. J Bas Chin Med, 2022, 28(4): 571-574+662.
38. Zhang K. The Traditional Chinese Medicine expression of defensive Qi and immune cells. Hubei J Trad Chin Med, 2001, 23(3): 3-4.
39. Wen C, Zheng Z, Shao T, et al. Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis. Genome Biol, 2017, 18(1): 142.
40. Chopra A, Shiheido-Watanabe Y, Eberhard J. Editorial: Porphyromonas gingivalis: molecular mechanisms of invasion, immune evasion, and dysbiosis. Front Cell Infect Microbiol, 2023, 13: 1289103.
41. Liu YW, Yuan X, Sun W, et al. Clinical significance and prognostic value of Porphyromonas gingivalis infection in lung cancer. J Jinan University(Natural Science & Medicine Edition), 2020, 41(3): 260-267.
42. Zhao Y, Ye Q, Feng Y, et al. Prevotella genus and its related NOD-like receptor signaling pathway in young males with stage Ⅲ periodontitis. Front Microbiol, 2022, 13: 1049525.
43. Zhang JH, Chen YC, Xu N, et al. Interpretation of the mechanism of Yu's Herbal Tea in the treatment of inflammation based on network pharmacology and molecular dockin. Special Wild Economic Animal and Plant Research, 2024, 46(01): 62-71.
44. Hong BY, Sobue T, Choquette L, et al. Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis. Microbiome, 2019, 7(1): 66.
45. Eriksson K, Lundmark A, Delgado LF, et al. Salivary microbiota and host-inflammatory Responses in periodontitis affected individuals with and without rheumatoid arthritis. Front Cell Infect Microbiol, 2022, 12: 841139.
46. Scanu M, Toto F, Petito V, et al. An integrative multi-omic analysis defines gut microbiota, mycobiota, and metabolic fingerprints in ulcerative colitis patients. Front Cell Infect Microbiol, 2024, 14: 1366192.
47. Bhardwaj RG, Al-Khabbaz A, Karched M. Cytokine induction of peripheral blood mononuclear cells by biofilms and biofilm supernatants of Granulicatella and Abiotrophia spp. Microb Pathog, 2018, 114: 90-94.
48. Irfan M, Delgado ZR, Frias-lopez J. The Oral Microbiome and Cancer. Front Immunol, 2020, 11: 591088.
49. Watanabe N, Yokoe S, Ogata Y, et al. Exposure to Porphyromonas gingivalis induces production of proinflammatory cytokine via TLR2 from human respiratory epithelial cells. J Clin Med, 2020, 9(11): 3433.
50. Liu YT, Li M, Ma ZP. Treatment of the inflammatory microenyironment of pulmonary nodules from phlegm. J Changchun University Chin Med, 2020, 36(4): 620-623.

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Latest ArticlesStudy on the correlation between the distribution of Traditional Chinese Medicine syndrome elements and salivary microbiota in patients with pulmonary nodules

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