Characteristics of LKDS and PBSS of KOA Based on the Enhancement of Inflammatory Response by TGF-β/Smad Pathway Inhibited

To Explore the Characteristics of LKD Syndrome and PBS Syndrome of Knee Osteoarthritis Which Based on the Enhancement of Inflammatory Response Caused by the Inhibition of TGF-β/Smad Signal Pathway

1. Through research and analysis, the levels of upstream and downstream factors related to TGF-β/Smad signaling pathway and inflammatory response factor related factors in serum, blood cells, articular fluid, urine, tongue covering and discarded tissues after surgery of patients with LKD syndrome and PBS syndrome of knee osteoarthritis were obtained, and the syndrome characteristics were further obtained.
2. Through research and analysis, the index levels of multiple omics detection in serum, blood cells, joint fluid, urine, tongue coating and discarded tissues of patients with LKD syndrome and PBS syndrome of knee osteoarthritis were obtained, and the syndrome characteristics were further obtained.
3. The severity of syndrome was quantified by syndrome score scale and the correlation between the above results and the syndrome score of patients with knee osteoarthritis with LKD syndrome and PBS syndrome was studied in combination with imaging characteristics.
4. To establish a "disease and syndrome cell model" and test relevant indicators to support the above research.
5. Through the analysis of the above research results, the possible mechanism is analyzed to provide an objective basis for the biological basis of the syndrome and relevant evidence for the clinical diagnosis and treatment of knee osteoarthritis with traditional Chinese medicine.

Study Overview

• Status: Recruiting
• Conditions: Syndrome; Knee Osteoarthritis; Traditional Chinese Medicine
• Intervention / Treatment: Other: cross-sectional study without intervention

Detailed Description

1. Through research and analysis, the levels of upstream and downstream factors related to TGF-β/Smad signaling pathway and inflammatory response factor related factors in serum, blood cells, articular fluid, urine, tongue covering and discarded tissues after surgery of patients with liver and kidney deficiency syndrome and phlegm and blood stasis syndrome of knee osteoarthritis were obtained, and the syndrome characteristics were further obtained.
2. Through research and analysis, the index levels of multiple omics detection in serum, blood cells, joint fluid, urine, tongue coating and discarded tissues of patients with liver and kidney deficiency syndrome and phlegm and blood stasis syndrome of knee osteoarthritis were obtained, and the syndrome characteristics were further obtained.
3. The severity of syndrome was quantified by syndrome score scale and the correlation between the above results and the syndrome score of patients with knee osteoarthritis with liver and kidney deficiency syndrome and phlegm and blood stasis syndrome was studied in combination with imaging characteristics.
4. To establish a "disease and syndrome cell model" and test relevant indicators to support the above research.
5. Through the analysis of the above research results, the possible mechanism is analyzed to provide an objective basis for the biological basis of the syndrome and relevant evidence for the clinical diagnosis and treatment of knee osteoarthritis with traditional Chinese medicine.

• Study Type: Observational
• Enrollment (Anticipated): 340

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100700
      • Recruiting
      • Dongzhimen Hospital
      • Contact: Rui Zheng; Phone Number: +8601084012709; Email: yechao@bucm.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Among the outpatients and inpatients in Dongzhimen Hospital of Beijing University of traditional Chinese medicine from December 2021 to August 2024, 150 cases of liver and kidney deficiency syndrome and 300 cases of phlegm and blood stasis syndrome were taken respectively. All patients met the diagnosis of knee osteoarthritis and met the inclusion criteria. Another 40 cases of normal control group were taken.

Description

Inclusion Criteria:

1. Inclusion criteria of liver and kidney deficiency syndrome and phlegm and blood stasis syndrome in knee osteoarthritis

   • Age 20-80 years old, in line with the diagnostic criteria of Western medicine;
   • In accordance with the diagnostic criteria of TCM syndromes, it belongs to liver and kidney deficiency syndrome and phlegm and blood stasis syndrome;
   • Patients who are willing to participate in the survey and have good compliance;
   • Voluntary signing of informed consent;

2. Inclusion criteria of normal control group

   • Age 20-80 years old.
   • Patients who are willing to participate in the survey and have good compliance.
   • It does not meet the diagnostic criteria of knee osteoarthritis.
   • Voluntarily sign informed consent.

Exclusion Criteria:

• Complications affecting joints, such as psoriasis, syphilitic neuropathy, brown yellow disease, metabolic bone disease, etc;
• There were rheumatoid arthritis and ankylosing spondylitis;
• Late disabled and incapacitated;
• Pregnant or lactating women;
• Mentally ill.
• As long as one of the above 5 articles is met, it shall be excluded.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
LKD syndrome; liver and kidney deficiency syndrome	Other: cross-sectional study without intervention; cross-sectional study without intervention
PBS syndrome; phlegm and blood stasis syndrome	Other: cross-sectional study without intervention; cross-sectional study without intervention
NC group; Normal Control group	Other: cross-sectional study without intervention; cross-sectional study without intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the differences of metabonomics	The differences of metabonomics in blood, urine and tongue coating will be detected by metabonomics in LKD group, PBS group and NC group.	3 years
the differences of metabonomics in the cell models of disease-TCM syndrome	The differences of metabonomics in the cell models of disease-TCM syndrome will be detected by metabonomics.	3 years
the differences of proteomics in the cell models of disease-TCM syndrome	The differences of proteomics in the cell models of disease-TCM syndrome will be detected by proteomics.	3 years
the differences of proteomics	The differences of proteomics in blood, urine and tongue coating will be detected by proteomics in LKD group, PBS group and NC group.	3 years
the differences of transcriptomics	The differences of transcriptomics in blood, urine and tongue coating will be detected by transcriptomics in LKD group, PBS group and NC group.	3 years
the differences of transcriptomics in the cell models of disease-TCM syndrome	The differences of transcriptomics in the cell models of disease-TCM syndrome will be detected by transcriptomics.	3 years
the related indexes of TGF- β/ Smad signaling pathway and inflammatory response	Histological and pathological examination is used to detect the related indexes of TGF- β/ Smad signaling pathway and inflammatory response.	3 years
The clinical TCM scores of LKD	The minimum value is 0 and maximum value is 38, and higher scores mean a worse outcome.	3 years
The clinical TCM scores of PBS	The minimum value is 0 and maximum value is 41, and higher scores mean a worse outcome.	3 years
The grading scores of Kellgren Lawrence (K-L)	The minimum value is 0 and maximum value is 4, and higher scores mean a worse outcome.	3 years
The grading scores of Yulish	The minimum value is 0 and maximum value is 4, and higher scores mean a worse outcome.	3 years
Clinical data	Collect clinical data and formulate a unified questionnaire, including the name, age, gender, outpatient / inpatient number, past history, current medical history, imaging images and other relevant data of patients with knee osteoarthritis.	3 years
Concentration of BLC (CXCL13)	Concentration of BLC (CXCL13) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of BLC (CXCL13) in the cell models of disease-TCM syndrome	Concentration of BLC (CXCL13) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of Eotaxin-1 (CCL11)	Concentration of Eotaxin-1 (CCL11) will be detected by ELISA will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of Eotaxin-1 (CCL11) in the cell models of disease-TCM syndrome	Concentration of Eotaxin-1 (CCL11) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of Eotaxin-2 (MPIF-2/CCL24)	Concentration of Eotaxin-2 (MPIF-2/CCL24) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of Eotaxin-2 (MPIF-2/CCL24) in the cell models of disease-TCM syndrome	Concentration of Eotaxin-2 (MPIF-2/CCL24) will be detected by ELISA in the cell models of disease-TCM.	3 years
Concentration of GCSF	Concentration of GCSF will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of GCSF in the cell models of disease-TCM syndrome	Concentration of GCSF will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of GM-CSF	Concentration of GM-CSF will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of GM-CSF in the cell models of disease-TCM syndrome	Concentration of GM-CSF will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of I-309 (TCA-3/CCL1)	Concentration of I-309 (TCA-3/CCL1) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of I-309 (TCA-3/CCL1) in the cell models of disease-TCM syndrome	Concentration of I-309 (TCA-3/CCL1) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of ICAM-1(CD54)	Concentration of ICAM-1(CD54) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of ICAM-1(CD54) in the cell models of disease-TCM syndrome	Concentration of ICAM-1(CD54) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IFN-gamma	Concentration of IFN-gamma will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IFN-gamma in the cell models of disease-TCM syndrome	Concentration of IFN-gamma will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-1 alpha (IL-1 F1)	Concentration of IL-1 alpha (IL-1 F1) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-1 alpha (IL-1 F1) in the cell models of disease-TCM syndrome	Concentration of IL-1 alpha (IL-1 F1) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-1 beta (IL-1 F2)	Concentration of IL-1 beta (IL-1 F2) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-1 beta (IL-1 F2) in the cell models of disease-TCM syndrome	Concentration of IL-1 beta (IL-1 F2) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-1 ra (IL-1 F3)	Concentration of IL-1 ra (IL-1 F3) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-1 ra (IL-1 F3) in the cell models of disease-TCM syndrome	Concentration of IL-1 ra (IL-1 F3) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-2	Concentration of IL-2 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-2 in the cell models of disease-TCM syndrome	Concentration of IL-2 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-4	Concentration of IL-4 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-4 in the cell models of disease-TCM syndrome	Concentration of IL-4 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-5	Concentration of IL-5 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-5 in the cell models of disease-TCM syndrome	Concentration of IL-5 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-6	Concentration of IL-6 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-6 in the cell models of disease-TCM syndrome	Concentration of IL-6 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-6R	Concentration of IL-6R will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-6R in the cell models of disease-TCM syndrome	Concentration of IL-6R will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-7	Concentration of IL-7 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-7 in the cell models of disease-TCM syndrome	Concentration of IL-7 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-8(CXCL8)	Concentration of IL-8(CXCL8) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-8(CXCL8) in the cell models of disease-TCM syndrome	Concentration of IL-8(CXCL8) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-10	Concentration of IL-10 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-10 in the cell models of disease-TCM syndrome	Concentration of IL-10 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-11	Concentration of IL-11 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-11 in the cell models of disease-TCM syndrome	Concentration of IL-11 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-12 p40	Concentration of IL-12 p40 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-12 p40 in the cell models of disease-TCM syndrome	Concentration of IL-12 p40 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-12 p70	Concentration of IL-12 p70 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-12 p70 in the cell models of disease-TCM syndrome	Concentration of IL-12 p70 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-13	Concentration of IL-13 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-13 in the cell models of disease-TCM syndrome	Concentration of IL-13 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-15	Concentration of IL-15 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-15 in the cell models of disease-TCM syndrome	Concentration of IL-15 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-16	Concentration of IL-16 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-16 in the cell models of disease-TCM syndrome	Concentration of IL-16 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of IL-17A	Concentration of IL-17A will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of IL-17A in the cell models of disease-TCM syndrome	Concentration of IL-17A will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of MCP-1 (CCL2)	Concentration of MCP-1 (CCL2) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of MCP-1 (CCL2) in the cell models of disease-TCM syndrome	Concentration of MCP-1 (CCL2) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of M-CSF	Concentration of M-CSF will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of M-CSF in the cell models of disease-TCM syndrome	Concentration of M-CSF will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of MIG (CXCL9)	Concentration of MIG (CXCL9) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of MIG (CXCL9) in the cell models of disease-TCM syndrome	Concentration of MIG (CXCL9) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of MIP-1	Concentration of MIP-1 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of MIP-1 in the cell models of disease-TCM syndrome	Concentration of MIP-1 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of alpha (CCL3) in the cell models of disease-TCM syndrome	Concentration of alpha (CCL3) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of alpha (CCL3)	Concentration of alpha (CCL3) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of MIP-1 beta (CCL4)	Concentration of MIP-1 beta (CCL4) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of MIP-1 beta (CCL4) in the cell models of disease-TCM syndrome	Concentration of MIP-1 beta (CCL4) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of MIP-1 delta (CCL15)	Concentration of MIP-1 delta (CCL15) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of MIP-1 delta (CCL15) in the cell models of disease-TCM syndrome	Concentration of MIP-1 delta (CCL15) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of PDGF-BB	Concentration of PDGF-BB will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of PDGF-BB in the cell models of disease-TCM syndrome	Concentration of PDGF-BB will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of RANTES (CCL5)	Concentration of RANTES (CCL5) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of RANTES (CCL5) in the cell models of disease-TCM syndrome	Concentration of RANTES (CCL5) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of TIMP-1	Concentration of TIMP-1 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of TIMP-1 in the cell models of disease-TCM syndrome	Concentration of TIMP-1 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of TIMP-2	Concentration of TIMP-2 will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of TIMP-2 in the cell models of disease-TCM syndrome	Concentration of TIMP-2 will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of TNF alpha	Concentration of TNF alpha will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of TNF alpha in the cell models of disease-TCM syndrome	Concentration of TNF alpha will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of TNF beta (TNFSF1B)	Concentration of TNF beta (TNFSF1B) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of TNF beta (TNFSF1B) in the cell models of disease-TCM syndrome	Concentration of TNF beta (TNFSF1B) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of TNF RI (TNFRSF1A)	Concentration of TNF RI (TNFRSF1A) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of TNF RI (TNFRSF1A) in the cell models of disease-TCM syndrome	Concentration of TNF RI (TNFRSF1A) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of TNF RII(TNFRSF1B)	Concentration of TNF RII(TNFRSF1B) will be detected by ELISA in LKD group, PBS group and NC group.	3 years
Concentration of TNF RII(TNFRSF1B) in the cell models of disease-TCM syndrome	Concentration of TNF RII(TNFRSF1B) will be detected by ELISA in the cell models of disease-TCM syndrome.	3 years
Concentration of Signaling pathway indicator	Concentration of Signaling pathway indicator will be detected by ELISA, metabonomics, proteomics, transcriptomics in LKD group, PBS group and NC group.	3 years
Concentration of Signaling pathway indicator in the cell models of disease-TCM syndrome	Concentration of Signaling pathway indicator will be detected by ELISA, metabonomics, proteomics, transcriptomics in the cell models of disease-TCM syndrome.	3 years
Concentration of Routine Blood Examination （Concentration of WBC, LYMPH%, MONO, NEUT%, LYMPH, MONO%, NEUT, BASO%, BASO, MCH, MCHC,ROW-CV, MPV, PLT, PDW, EO%, P-LCR, RBC, Hb, HCT）	LKD group, PBS group and NC group's Routine Blood Examination will be detect by automated hematology analyzer.	3 years
Concentration of Blood Biochemistry (Concentration of TC, TG, HDL-C, LDL-C, Urea, Cr, UA, GLu, ALT, AST, TP, ALB, ALP, GGT, TBIL, DBIL, Mg, K, Na, Cl, Ca, P, Fe, CO2)	LKD group, PBS group and NC group's Blood Biochemistry will be detect by automatic biochemical analyzer.	3 years
Concentration of Routine Urine Examination (Concentration of LEU, NIT, PRO, GLU-U, KET, URO, BIL, PH-U, SG, BLU)	LKD group, PBS group and NC group's Routine Urine Examination will be detect by Urine analyzer.	3 years

Collaborators and Investigators

• Sponsor: Dongzhimen Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2021
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: December 27, 2021
• First Submitted That Met QC Criteria: January 28, 2022
• First Posted (Actual): February 1, 2022

Study Record Updates

• Last Update Posted (Actual): February 1, 2022
• Last Update Submitted That Met QC Criteria: January 28, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: knee osteoarthritis; traditional Chinese medicine; syndrome; TGF-β/Smad signaling pathway; disease and syndrome cell model
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Syndrome; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: 2021DZMEC-139-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No