Abstract
The aim of this study was to investigate the clinical value of the platelet-to-lymphocyte ratio (PLR) in rheumatoid arthritis (RA) and the effects of Xin'an Jianpi Tongbi Formulation (XAJPF) [containing Xinfeng Capsule (XFC) and Huangqinqingrechubi Capsule (HQC)] on the Self-Perception of Patient (SPP) - a multidimensional construct encompassing patient-reported outcomes and traditional Chinese medicine (TCM) syndrome evaluations - and laboratory indices in patients with RA. A cohort study design was used, and the study data were obtained from RA patients admitted to the Department of Rheumatology of the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from February 2024 to March 2025. General information (gender, age, BMI, disease duration, co-morbidities), PLR (platelets/Lymphocyte), laboratory indicators [mean platelet volume (MPV), platelet distribution width (PDW), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), hypersensitive C-reactive protein (hs-CRP), alanine aminotransferase (ALT), aspartate transaminase (AST), serum creatinine (Scr), blood urea nitrogen (BUN)], and SPP indicators were collected through the medical record system. The SPP scales included the MOS item short from health survey (SF-36), visual analogue scale (VAS), Self-Rating Anxiety scale (SAS), Self-Rating Depression scale (SDS), Chinese medicine evidence scores (cold-dampness syndrome [CDS], syndrome of dampness-heat [SDH], syndrome of blood stasis [SBS], and syndrome of dampness stagnancy due to spleen deficiency [SDSSD]). Correlation analysis was used to study the correlation between PLR and laboratory indicators and SPP indicators. Binary Logistics regression models were used to assess the risk and protective factors for SPP changes in RA patients. Mediation analysis was used to investigate the mediating role that PLR acted as in the improvement of SPP by XAJPF. Association rule analysis was used to explore the association of PLR reduction with other laboratory indices and SPP improvement, as well as the association of XAJPF treatment with improvement in SPP indices and laboratory indices in RA patients. Finally, subgroup analyses were used to observe the effects of different exposure levels on SPP indicators and laboratory indicators in RA patients. The results of correlation analysis showed a significant negative correlation between PLR and BP, VT, SF, and MH, and a significant positive correlation with VAS, Chinese patient-eported activity index with rheumatoid arthritis (CPRI-RA), SAS, SDS, SDH, and SDSSD. There were 183 and 185 RA patients in the non-exposed (XAJPF Unused) and exposed groups (XAJPF Used), respectively. Compared with pretreatment, the levels of PF, RP, BP, GH, VT, SF, RE and MH increased and the levels of VAS, CPRI-RA, SAS, SDS, CDS, SDH, SDSSD and SBS decreased in both groups after treatment. The levels of PLR, MPV, PDW, ESR, RF and hs-CRP in laboratory indices were decreased. Liver and kidney function parameters remained within the normal range despite transient, statistically significant increases in alanine aminotransferase (ALT) and aspartate transaminase (AST). In addition, the improvements in PF, RP, BP, VT, RE, MH, VAS, CPRI-RA, SAS, SDS, CDS, SDH, SDSSD, and SBS were significantly greater in the exposed group than in the non-exposed group. Inflammatory markers (hs-CRP, ESR, RF, PLR) improved similarly in both groups. Binary logistic regression analysis showed that use of XAJPF was a protective factor for improvement in GH, VT, SF, RE, and SDSSD, and improvement in PLR was a protective factor for improvement in PF, GH, VT, SDS, and SDSSD. In the mediation analysis, PLR and XAJPF played a partial mediating role in improving GH and VT, and a complete mediating role in improving SDSSD. Association rule analysis showed that PLR reduction was associated with improvement in other laboratory indicators and SPP indicators, and the application of XAJPF was associated with improvement in PF, RP, BP, VT, RE, MH, VAS, CPRI-RA, SAS, SDS, CDS, SDH, SDSSD, SBS, PLR, MPV, PDW, ESR, RF, and hs-CRP Highly correlated. Subgroup analyses showed that there were 36 and 149 RA patients in the high-exposure and low-exposure groups, respectively, and that compared with the pretreatment period, both groups had elevated levels of PF, RP, BP, GH, VT, SF, RE, and MH, and increased levels of VAS, CPRI-RA, SAS, SDS, CDS, SDH, SDSSD, SBS, PLR, MPV, PDW, ESR, and RF, hs-CRP were reduced. In addition to this, exploratory analysis suggested that VT, MH, CPRI-RA, SDS, and SDH improved more significantly in the high-exposure group compared to the low-exposure group after treatment. However, the smaller sample size of the high-exposure group (n = 36) necessitates cautious interpretation of these findings. PLR in RA patients is correlated with SPP and laboratory parameters. XAJPF treatment can significantly improve SPP indicators. Inflammatory markers improved similarly in both XAJPF and control groups. XAJPF may improve VT, GH, and SDSSD partly through reducing PLR. Exploratory analysis suggested that high-exposure regimens might offer additional benefits for VT, MH, CPRI-RA, SDS, and SDH, warranting further confirmation.