A total of 240 patients with rheumatoid arthritis from Jingzhou First People’s Hospital from May 2024 to May 2025 were selected as research subjects.

Inclusion criteria: (1) Patients with rheumatoid arthritis who can tolerate joint aspiration and have no contraindications to treatment with Yixin Sai. (2) Meet the clinical diagnostic criteria for rheumatoid arthritis, all using low-dose glucocorticoids + methotrexate tablets to control the condition. (3) Meet the criteria for rheumatoid arthritis with knee involvement, MSUS ultrasound scores are identical (baseline musculoskeletal ultrasound total score ≥5 points (semi-quantitative scoring system [8]); at least 2 positive ultrasound findings (synovial hyperplasia ≥2 points + blood flow signal ≥1 point or bone erosion ≥1 point); bilateral knee scores difference ≤1 point (if bilateral knee treatment is involved). (4) Approved by the hospital ethics committee, patients and their families provide informed consent and cooperate well.

Exclusion Criteria: (1) Target knee deformity, X-ray showing moderate to severe subchondral bone destruction or joint space <3 mm; (2) Received intra-articular injections of hormones, TNF antagonists, joint replacement, or synovectomy within 8 weeks; (3) Currently suffering from active pulmonary tuberculosis, hepatitis B virus infection; patients with other autoimmune diseases, diabetes, and severe cardiac, hepatic, or renal dysfunction; (4) Pregnant, breastfeeding, or at risk of pregnancy; (5) Individuals with contraindications to puncture.

2.2.1. Patient Grouping

The patients were divided into two groups: the control group of 120 patients received treatment with prednisone tablets 10 mg qd + methotrexate 10mg once a week; the intra-articular injection group of 120 patients received treatment with prednisone tablets 10 mg qd + methotrexate tablets 10mg once a week + combined ultrasound-guided knee joint puncture injection of TNF-α antagonist (Yisepu injection) 25 mg.

2.2.2. Interventional Therapy

Under ultrasound guidance, select an appropriate puncture site. After routine disinfection, draping, and anesthesia, puncture the joint capsule. Use a 5 ml sterile syringe to aspirate any fluid from the joint cavity and then inject 1 ml of Yisai (25 mg/ml). Withdraw the needle and apply pressure to stop bleeding locally, followed by wrapping the joint with an elastic bandage. Instruct the patient to avoid strenuous movement of the joint for one week.

The knee MSUS ultrasound score, serum indicators such as erythrocyte sedimentation rate, C-reactive protein and DAS28 score of the three groups of patients in January, March and June were collected to observe the efficacy of the patients.

Detection Method

Using the Konica Minolta color Doppler ultrasound diagnostic instrument, a 9L4 linear array probe with a frequency of 7 - 12 MHz and MSK conditions was used. The imaging depth and focus were both adjusted to the near field. The wall filter was set to low-pass filtering, the pulse repetition rate was 977 Hz, and the energy Doppler settings were optimized for sensitivity without producing artifacts just below the cortical bone. The patient was placed in a supine position for knee joint examination. The semi-quantitative score [8] of musculoskeletal ultrasound: This was completed by an experienced doctor (with at least 5 years of work experience) from our department, who removed patient information and treatment markers from the original images before performing the knee joint MSUS examination.

Ultrasound semi-quantitative evaluation methods: (1) Synovial hyperplasia, normal is 0 points; synovial hyperplasia limited to the joint angle and not exceeding the line connecting the highest points of the drum membrane is 1 point; synovial hyperplasia extending beyond the highest point of the bone surface but not reaching the shaft is 2 points; synovial hyperplasia extending to the shaft is 3 points; (2) Bone erosion, normal is 0 points; roughness on the cortical surface without defect is 1 point; significant bone defect is 2 points; large bone defect area is 3 points; (3) Joint effusion, normal is 0 points; minimal is 1 point; moderate is 2 points; significant is 3 points; (4) Blood flow signal within the synovium, normal is 0 points; single blood flow signal is 1 point; blood flow signal less than 50% of the synovial area is 2 points; blood flow signal greater than 50% of the synovial area is 3 points. All enrolled patients met the preset homogeneity requirements for baseline MSUS scores (treatment group 7.05 ± 2.16 vs control group 7.10 ± 2.08, P = 0.856), with specific distribution see Table 1.

Laboratory tests: Fasted venous blood was collected from all patients, and C-reactive protein (CRP), ESR, knee MSUS score and DAS28 score were compared between the two groups.

The statistical data were analyzed by SPSS 19.0 statistical software, and the measurement data were expressed as x ± s. The t-test of group design was used to compare the differences, and P < 0.05 was considered as statistically significant.

Before treatment, there were no statistically significant differences in various knee ultrasound evaluation indicators between the two groups (P > 0.05). At 3 and 6 months post-treatment, the synovial hyperplasia, bone erosion, joint effusion, and synovial blood flow signal scores of patients in the intra-articular injection group were significantly lower than those in the control group, with statistically significant differences (P < 0.05) see Table 1.

Table 1. Comparison of ultrasound evaluation indexes of knee joints in two groups of patients (x ± s, points).

Note: * indicates that compared with the pre-treatment of the same group, P < 0.05; repeated measurement ANOVA was used for inter-group comparison.

There was no significant difference in serum CRP and ESR levels between the two groups before treatment (P > 0.05). After treatment, the CRP and ESR levels of patients in the joint cavity injection group were significantly lower than those in the control group, and the difference was statistically significant (P < 0.05) See Table 2.

Table 2. Comparison of serological indexes between the two groups.

Note: * indicates compared with the same group before treatment, P < 0.05; data are expressed as M (P25, P75); inter-group comparison is Mann-Whitney U test.

There was no significant difference in DAS28 score between the two groups before treatment (P > 0.05). After treatment, the DAS28 score of patients in the joint cavity injection group was significantly lower than that of the control group, and the difference was statistically significant (P < 0.05) see Table 3.

Table 3. Comparison of DAS28 scores between the two groups (x ± s, points).

Note: * indicates that compared with the pre-treatment of the same group, P < 0.05; inter-group comparison was performed by independent sample t-test.

Table 4. Comparison of adverse reactions in the two groups [case (%)].

Note: χ² test was used for inter-group comparison.

During the treatment, no serious adverse reactions (events leading to hospitalization, loss of function or life-threatening events) occurred in either group. No injection-related adverse reactions occurred in the joint cavity injection group, and there was no statistically significant difference in the incidence of adverse reactions between the two groups (P > 0.05) see Table 4.

Traditional joint aspiration techniques primarily rely on the doctor’s experience and tactile sense, which can be somewhat blind, leading to inaccurate drug injection and increasing the risk of complications. Ultrasound-guided joint aspiration technology enables “visual” manipulation, allowing doctors to accurately select puncture sites under ultrasound guidance, observe the drug injection process, and ensure precise delivery into the joint cavity, thereby enhancing the accuracy and safety of the injection [9]. The results of this study show that patients in the joint aspiration group did not experience significant adverse reactions during treatment, further confirming the safety of ultrasound-guided joint aspiration.

TNF-α is an important pro-inflammatory cytokine that plays a crucial role in the pathogenesis of rheumatoid arthritis. TNF-α promotes the proliferation of synovial fibroblasts through the activation of the NF-κB pathway [6]. In this study, the reduced score of synovial blood flow signals may be associated with local inhibition of VEGF secretion. TNF-α antagonists can specifically bind to TNF-α, blocking its biological activity and thus inhibiting inflammatory responses and reducing joint damage [10]. The results of this study indicate that intra-articular injection of TNF-α antagonists can significantly improve patients’ knee MSUS ultrasound scores, serological markers, and DAS28 scores, demonstrating the significant efficacy of TNF-α antagonists in the treatment of rheumatoid arthritis.

Musculoskeletal ultrasound, as a non-invasive diagnostic method, can clearly display the structure and lesions of joints, making it valuable for the diagnosis, treatment, and efficacy evaluation of rheumatoid arthritis [11]. This study used a semi-quantitative scoring method with musculoskeletal ultrasound to assess patients’ knee joints. The results showed that the MSUS ultrasound scores of the knee joints in the intra-articular injection group significantly improved at both 3 months and 6 months post-treatment, indicating that musculoskeletal ultrasound can accurately reflect changes in the patient’s condition, providing an objective basis for clinical treatment.

This study has certain limitations. First, the sample size is relatively small, and the observation period was short; a 6-month follow-up is insufficient to evaluate cartilage repair (a follow-up of at least 12 months with MRI is required), which may affect the reliability of the results. Second, this study only observed the efficacy and safety of TNF-α antagonists injected into the knee joint cavity, and further research is needed for their efficacy in other joints. Additionally, this study did not follow up on patients’ long-term outcomes, and future studies with larger samples and longer durations are needed to further validate the efficacy and safety of TNF-α antagonists injected under ultrasound guidance into the joint cavity.

Although strict MSUS scoring criteria were used to ensure baseline comparability, the lack of more accurate blood flow quantification methods such as dynamic enhanced ultrasound may affect the sensitivity of activity assessment. Future studies could combine angiographic ultrasound to improve stratification accuracy.