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

Sponsor

Dongzhimen Hospital, Beijing (Other)

Overall Status

Recruiting

CT.gov ID

NCT05218122

Collaborator

(none)

340

Enrollment

Location

36.2

Anticipated Duration (Months)

9.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.
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.
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.
To establish a "disease and syndrome cell model" and test relevant indicators to support the above research.
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.

Condition or Disease	Intervention/Treatment	Phase
Knee Osteoarthritis Syndrome Traditional Chinese Medicine	Other: cross-sectional study without intervention

Detailed Description

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.
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.
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.
To establish a "disease and syndrome cell model" and test relevant indicators to support the above research.
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 Design

Study Type:

Observational

Anticipated Enrollment :

340 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Dec 24, 2021

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	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

Arm

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

Outcome Measures

Primary Outcome Measures

the differences of metabonomics [3 years]
The differences of metabonomics in blood, urine and tongue coating will be detected by metabonomics in LKD group, PBS group and NC group.
the differences of metabonomics in the cell models of disease-TCM syndrome [3 years]
The differences of metabonomics in the cell models of disease-TCM syndrome will be detected by metabonomics.
the differences of proteomics in the cell models of disease-TCM syndrome [3 years]
The differences of proteomics in the cell models of disease-TCM syndrome will be detected by proteomics.
the differences of proteomics [3 years]
The differences of proteomics in blood, urine and tongue coating will be detected by proteomics in LKD group, PBS group and NC group.
the differences of transcriptomics [3 years]
The differences of transcriptomics in blood, urine and tongue coating will be detected by transcriptomics in LKD group, PBS group and NC group.
the differences of transcriptomics in the cell models of disease-TCM syndrome [3 years]
The differences of transcriptomics in the cell models of disease-TCM syndrome will be detected by transcriptomics.
the related indexes of TGF- β/ Smad signaling pathway and inflammatory response [3 years]
Histological and pathological examination is used to detect the related indexes of TGF- β/ Smad signaling pathway and inflammatory response.
The clinical TCM scores of LKD [3 years]
The minimum value is 0 and maximum value is 38, and higher scores mean a worse outcome.
The clinical TCM scores of PBS [3 years]
The minimum value is 0 and maximum value is 41, and higher scores mean a worse outcome.
The grading scores of Kellgren Lawrence (K-L) [3 years]
The minimum value is 0 and maximum value is 4, and higher scores mean a worse outcome.
The grading scores of Yulish [3 years]
The minimum value is 0 and maximum value is 4, and higher scores mean a worse outcome.
Clinical data [3 years]
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.
Concentration of BLC (CXCL13) [3 years]
Concentration of BLC (CXCL13) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of BLC (CXCL13) in the cell models of disease-TCM syndrome [3 years]
Concentration of BLC (CXCL13) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of Eotaxin-1 (CCL11) [3 years]
Concentration of Eotaxin-1 (CCL11) will be detected by ELISA will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of Eotaxin-1 (CCL11) in the cell models of disease-TCM syndrome [3 years]
Concentration of Eotaxin-1 (CCL11) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of Eotaxin-2 (MPIF-2/CCL24) [3 years]
Concentration of Eotaxin-2 (MPIF-2/CCL24) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of Eotaxin-2 (MPIF-2/CCL24) in the cell models of disease-TCM syndrome [3 years]
Concentration of Eotaxin-2 (MPIF-2/CCL24) will be detected by ELISA in the cell models of disease-TCM.
Concentration of GCSF [3 years]
Concentration of GCSF will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of GCSF in the cell models of disease-TCM syndrome [3 years]
Concentration of GCSF will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of GM-CSF [3 years]
Concentration of GM-CSF will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of GM-CSF in the cell models of disease-TCM syndrome [3 years]
Concentration of GM-CSF will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of I-309 (TCA-3/CCL1) [3 years]
Concentration of I-309 (TCA-3/CCL1) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of I-309 (TCA-3/CCL1) in the cell models of disease-TCM syndrome [3 years]
Concentration of I-309 (TCA-3/CCL1) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of ICAM-1(CD54) [3 years]
Concentration of ICAM-1(CD54) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of ICAM-1(CD54) in the cell models of disease-TCM syndrome [3 years]
Concentration of ICAM-1(CD54) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IFN-gamma [3 years]
Concentration of IFN-gamma will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IFN-gamma in the cell models of disease-TCM syndrome [3 years]
Concentration of IFN-gamma will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-1 alpha (IL-1 F1) [3 years]
Concentration of IL-1 alpha (IL-1 F1) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-1 alpha (IL-1 F1) in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-1 alpha (IL-1 F1) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-1 beta (IL-1 F2) [3 years]
Concentration of IL-1 beta (IL-1 F2) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-1 beta (IL-1 F2) in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-1 beta (IL-1 F2) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-1 ra (IL-1 F3) [3 years]
Concentration of IL-1 ra (IL-1 F3) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-1 ra (IL-1 F3) in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-1 ra (IL-1 F3) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-2 [3 years]
Concentration of IL-2 will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-2 in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-2 will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-4 [3 years]
Concentration of IL-4 will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-4 in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-4 will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-5 [3 years]
Concentration of IL-5 will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-5 in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-5 will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-6 [3 years]
Concentration of IL-6 will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-6 in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-6 will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-6R [3 years]
Concentration of IL-6R will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-6R in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-6R will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-7 [3 years]
Concentration of IL-7 will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-7 in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-7 will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-8(CXCL8) [3 years]
Concentration of IL-8(CXCL8) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-8(CXCL8) in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-8(CXCL8) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-10 [3 years]
Concentration of IL-10 will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-10 in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-10 will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-11 [3 years]
Concentration of IL-11 will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-11 in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-11 will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-12 p40 [3 years]
Concentration of IL-12 p40 will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-12 p40 in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-12 p40 will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-12 p70 [3 years]
Concentration of IL-12 p70 will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-12 p70 in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-12 p70 will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-13 [3 years]
Concentration of IL-13 will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-13 in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-13 will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-15 [3 years]
Concentration of IL-15 will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-15 in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-15 will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-16 [3 years]
Concentration of IL-16 will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-16 in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-16 will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of IL-17A [3 years]
Concentration of IL-17A will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of IL-17A in the cell models of disease-TCM syndrome [3 years]
Concentration of IL-17A will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of MCP-1 (CCL2) [3 years]
Concentration of MCP-1 (CCL2) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of MCP-1 (CCL2) in the cell models of disease-TCM syndrome [3 years]
Concentration of MCP-1 (CCL2) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of M-CSF [3 years]
Concentration of M-CSF will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of M-CSF in the cell models of disease-TCM syndrome [3 years]
Concentration of M-CSF will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of MIG (CXCL9) [3 years]
Concentration of MIG (CXCL9) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of MIG (CXCL9) in the cell models of disease-TCM syndrome [3 years]
Concentration of MIG (CXCL9) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of MIP-1 [3 years]
Concentration of MIP-1 will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of MIP-1 in the cell models of disease-TCM syndrome [3 years]
Concentration of MIP-1 will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of alpha (CCL3) in the cell models of disease-TCM syndrome [3 years]
Concentration of alpha (CCL3) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of alpha (CCL3) [3 years]
Concentration of alpha (CCL3) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of MIP-1 beta (CCL4) [3 years]
Concentration of MIP-1 beta (CCL4) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of MIP-1 beta (CCL4) in the cell models of disease-TCM syndrome [3 years]
Concentration of MIP-1 beta (CCL4) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of MIP-1 delta (CCL15) [3 years]
Concentration of MIP-1 delta (CCL15) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of MIP-1 delta (CCL15) in the cell models of disease-TCM syndrome [3 years]
Concentration of MIP-1 delta (CCL15) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of PDGF-BB [3 years]
Concentration of PDGF-BB will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of PDGF-BB in the cell models of disease-TCM syndrome [3 years]
Concentration of PDGF-BB will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of RANTES (CCL5) [3 years]
Concentration of RANTES (CCL5) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of RANTES (CCL5) in the cell models of disease-TCM syndrome [3 years]
Concentration of RANTES (CCL5) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of TIMP-1 [3 years]
Concentration of TIMP-1 will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of TIMP-1 in the cell models of disease-TCM syndrome [3 years]
Concentration of TIMP-1 will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of TIMP-2 [3 years]
Concentration of TIMP-2 will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of TIMP-2 in the cell models of disease-TCM syndrome [3 years]
Concentration of TIMP-2 will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of TNF alpha [3 years]
Concentration of TNF alpha will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of TNF alpha in the cell models of disease-TCM syndrome [3 years]
Concentration of TNF alpha will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of TNF beta (TNFSF1B) [3 years]
Concentration of TNF beta (TNFSF1B) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of TNF beta (TNFSF1B) in the cell models of disease-TCM syndrome [3 years]
Concentration of TNF beta (TNFSF1B) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of TNF RI (TNFRSF1A) [3 years]
Concentration of TNF RI (TNFRSF1A) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of TNF RI (TNFRSF1A) in the cell models of disease-TCM syndrome [3 years]
Concentration of TNF RI (TNFRSF1A) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of TNF RII(TNFRSF1B) [3 years]
Concentration of TNF RII(TNFRSF1B) will be detected by ELISA in LKD group, PBS group and NC group.
Concentration of TNF RII(TNFRSF1B) in the cell models of disease-TCM syndrome [3 years]
Concentration of TNF RII(TNFRSF1B) will be detected by ELISA in the cell models of disease-TCM syndrome.
Concentration of Signaling pathway indicator [3 years]
Concentration of Signaling pathway indicator will be detected by ELISA, metabonomics, proteomics, transcriptomics in LKD group, PBS group and NC group.
Concentration of Signaling pathway indicator in the cell models of disease-TCM syndrome [3 years]
Concentration of Signaling pathway indicator will be detected by ELISA, metabonomics, proteomics, transcriptomics in the cell models of disease-TCM syndrome.
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） [3 years]
LKD group, PBS group and NC group's Routine Blood Examination will be detect by automated hematology analyzer.
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) [3 years]
LKD group, PBS group and NC group's Blood Biochemistry will be detect by automatic biochemical analyzer.
Concentration of Routine Urine Examination (Concentration of LEU, NIT, PRO, GLU-U, KET, URO, BIL, PH-U, SG, BLU) [3 years]
LKD group, PBS group and NC group's Routine Urine Examination will be detect by Urine analyzer.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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;

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.