Comparison of the efficacy and safety of MAKO robot-assisted total knee arthroplasty versus conventional manual total knee arthroplasty in uncomplicated unilateral total knee arthroplasty a single-centre retrospective analysis.

PURPOSE: To compare the efficacy and safety of MAKO robot-assisted total knee arthroplasty (MA-TKA) with conventional manual total knee arthroplasty (CM-TKA) in patients with end-stage knee osteoarthritis (KOA) during the early postoperative period. METHOD: A retrospective analysis was conducted on 22 patients with KOA who underwent MA-TKA and 26 patients who underwent CM-TKA from April 2023 to July 2023. Hip-knee-ankle angle (HKA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), American Knee Society Score (AKSS), Forgotten Joint Score-12 (FJS-12), visual analogue scale (VAS), and postoperative complications were recorded and compared between the two groups. RESULT: Both groups successfully completed the surgeries. In terms of radiographic parameters, postoperative one month LDFA and HKA in the MA-TKA group were significantly lower than those in the CM-TKA group (P < 0.05). At the one month follow-up, 19 patients (86.4%) in the MA-TKA group had an HKA less than 3°, compared to 20 patients (76.9%) in the CM-TKA group. Clinically, VAS scores at 24 h, 48 h, and 72 h postoperatively were lower in the MA-TKA group both at rest and during activity. At one month and three months postoperatively, AKSS Function Scores and FJS-12 scores in the MA-TKA group were significantly higher than those in the CM-TKA group (P < 0.05). Regarding postoperative complications, no complications occurred in the MA-TKA group, while one patient in the CM-TKA group experienced postoperative knee stiffness, which resolved after physical therapy, with no statistically significant difference (P > 0.05). CONCLUSION: Compared with conventional manual total knee arthroplasty, MAKO robot-assisted TKA demonstrates better short-term clinical efficacy, achieves better alignment planning, and maintains good safety.

The Effectiveness of Tuina in Relieving Pain, Negative Emotions, and Disability in Knee Osteoarthritis: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness of Tuina in relieving the pain, negative emotions, and disability of patients with knee osteoarthritis (KOA). DESIGN: Single-center, parallel, randomized controlled trial. SETTING: Shanghai Guanghua Integrated Chinese and Western Medicine Hospital, Shanghai, China. SUBJECTS: Adult patients with KOA who were able to speak Chinese and self-report symptoms were eligible. METHODS: A total of 104 patients were randomly allocated to receive the 6-week treatment of Tuina (Tuina group) or celecoxib (celecoxib group). Data on pain, negative emotions, and disability were collected at baseline, at week 2, 4, and 6, and follow-up (1 month after the last treatment). The primary outcomes were the pressure pain thresholds. The secondary outcomes were: (1) numerical rating scale at rest and with movement; (2) Hamilton Anxiety Scale; (3) Hamilton Depression Scale; (4) Western Ontario and McMaster Universities Osteoarthritis Index; and (5) clinical effective rate. The adverse events of the trial were evaluated. RESULTS: In total, 99 patients completed the follow-up. Generalized linear mixed models were constructed to analyse the between-group differences. Statistically significant differences were found in the interaction effects (P < .05). In evaluating the group effect, statistical differences were found at week 6 and follow-up (P < .05). Further, all variables showed a time effect (P < .05). A statistical difference in the clinical effective rate was found between the Tuina and celecoxib groups (P < .05). CONCLUSIONS: Tuina produced superior effects for pain, negative emotions, and disability over time, as compared to celecoxib in patients with KOA.

[Effect of Juanbi Qianggu Formula on biological behaviors of fibroblast-like synoviocytes in rheumatoid arthritis by regulating FGFR1 signaling pathway based on network pharmacology and cell function experiments].

This study aimed to explore the molecular mechanism of Juanbi Qianggu Formula(JBQGF), an empirical formula formulated by the prestigious doctor in traditional Chinese medicine, in the treatment of rheumatoid arthritis based on network pharmacology and cell function experiments. The main active components and targets of JBQGF were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Encyclopedia of Traditional Chinese Medicine(ETCM), and the core targets underwent functional enrichment analysis and signaling pathway analysis. Cytoscape 3.6.0 was used to construct a visualized "active component-target-signaling pathway" network of JBQGF. After screening, nine potential pathways of JBQGF were obtained, mainly including G protein-coupled receptor signaling pathway and tyrosine kinase receptor signaling pathway. As previously indicated, the fibroblast growth factor receptor 1(FGFR1) signaling pathway was highly activated in active fibroblast-like synoviocytes(FLS) in rheumatoid arthritis, and cell and animal experiments demonstrated that inhibition of the FGFR1 signaling pathway could significantly reduce joint inflammation and joint destruction in collagen-induced arthritis(CIA) rats. In terms of the tyrosine kinase receptor signal transduction pathway, the analysis of its target genes revealed that FGFR1 might be a potential target of JBQGF for rheumatoid arthritis treatment. The biological effect of JBQGF by inhibiting FGFR1 phosphorylation was preliminarily verified by Western blot, Transwell invasion assay, and pannus erosion assay, thereby inhibiting matrix metalloproteinase 2(MMP2) and receptor activator of nuclear factor-κB ligand(RANKL) and suppressing the invasion of fibroblasts in rheumatoid arthritis and erosive effect of pannus bone. This study provides ideas for searching potential targets of rheumatoid arthritis treatment and TCM drugs through network pharmacology.

[Effect of 28-day administration of Psoraleae Fructus water extract on early liver injury in rats].

This study aims to investigate the hepatotoxicity of Psoraleae Fructus water extract and the underlying mechanism in rats. Forty-eight rats were randomly assigned into four groups: a blank group and low-(BZGL, 6.25 g·kg~(-1)), medium-(BGZM, 12.5 g·kg~(-1)), and high-dose(BGZH, 25 g·kg~(-1)) Psoraleae Fructus water extract groups. The rats were treated for 28 days, and toxicity and mortality were observed daily. After 28 days, the rats were sacrificed, and the body weight, liver index, and liver-to-brain ratio were calculated. The morphological changes in the liver tissue were observed, and the serum levels of related biochemical indicators were measured. The results showed that compared with the blank group, Psoraleae Fructus water extracts of different doses decreased the body weight, increased the liver index and liver-to-brain ratio, and caused liver hypertrophy and pathological changes. Pathological examination revealed that the rats in Psoraleae Fructus water extract groups had bile duct hyperplasia, inflammatory cell infiltration, and liver cell fibrosis. Compared with the blank group, BGZL elevated the levels of alanine transaminase(ALT), α-glutathione S-transferase(α-GST), and total bile acid(TBA)(P<0.05), and BGZM and BGZH elevated the levels of ALT, TBA, α-GST, γ-glutamyl transferase(γ-GT), purine nucleoside phosphorylase(PNP), ornithine carbamoyltransferase(OCT), and arginase(ArgI)(P<0.05). Compared with the blank group, Psoraleae Fructus water extracts of different doses down-regulated the mRNA and protein levels of bile salt export pump(BSEP) and farnesoid X receptor(FXR) and up-regulated the mRNA and protein levels of tumor necrosis factor-α(TNF-α), nuclear factor kappaB(NF-κB), and cholesterol 7 alpha-hydroxylase(CYP7A1)(P<0.05). The results suggested that Psoraleae Fructus water extract caused toxicity in rats, showing a dose-toxicity relationship. Psoraleae Fructus water extract may cause liver damage, which may be due to its effect on liver bile acid secretion and induction of inflammation.

Geriatric Nutritional Risk Index as a Prognostic Factor of Patients with Non-Small Cell Lung Cancer: A Meta-Analysis.

Geriatric nutritional risk index (GNRI), a newly developed indicator of nutritional status retrieved by serum albumin concentration and ideal body weight, has been suggested as a prognostic factor for various malignancies. The aim of the study was to summarize the prognostic role of GNRI for patients with non-small cell lung cancer (NSCLC) in a meta-analysis. Cohort studies evaluating the relationship between GNRI at baseline and survival OF NSCLC were retrieved by search of PubMed, Embase, and Web of Science databases from inception to January 12, 2022. A conservative random-effect model incorporating the possible influence of between-study heterogeneity was used to pool the results. Eleven cohorts including 2865 patients with NSCLC were included. Compared to those with higher GNRI, NSCLC patients with lower GNRI were associated with poorer overall survival [OS, hazard ratio (HR): 2.39, 95% CI: 1.97-2.91, p<0.001; I2=29%), progression-free survival (HR: 1.94, 95% CI: 1.52-2.47, p<0.001; I2=29%), and cancer-specific survival (HR: 2.59, 95% CI: 1.55-4.35, p<0.001; I2=0%). Subgroup analyses showed that the significant association between lower GNRI and worse OS in patients with NSCLC was not affected by study characteristics including study location, design, cancer stage, treatment, or follow-up durations (p for subgroup effects all<0.001). In conclusion, a lower GNRI in patients with NSCLC may be a predictor of poor survival. Nutritional status indicated by GNRI may be important for the prognostic prediction of patients with NSCLC.

An efficient approach for the synthesis of 1,2-dihydroxanthones enabled by one-pot Claisen condensation/cyclization reactions.

1,2-Dihydroxanthones (DHXs) are core structures of natural products and useful building blocks in organic synthesis. So far, they have been less studied. In this report, a mild, efficient and green method for the synthesis of 1,2-dihydroxanthones has been developed in one pot through Claisen condensation and O-cyclization under waste-induced relay catalysis with minimum organic solvents. The by-product (HMDS or NH3·H2O) of the first step turned out to be the promoter for the second step, which could efficiently proceed in aqueous media without the addition of other catalysts. The reactions using trifluoroethyl salicylates could be performed under mild conditions to ensure the generation of vulnerable DHXs in high yields. The substrate scope is very broad regardless of the substituent type and its position on the structure. Specifically, the versatility of DHXs was demonstrated by their conversion to xanthones and other complex structures.

Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rheumatoid arthritis: a randomized controlled study.

BACKGROUND: We aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA). METHODS: For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50-75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay. RESULTS: The mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P <  0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05). CONCLUSION: In patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR1900025013 ).

LncRNA HOTAIR-mediated Wnt/ß-catenin network modeling to predict and validate therapeutic targets for cartilage damage.

BACKGROUND: Cartilage damage is a crucial feature involved in several pathological conditions characterized by joint disorders, such as osteoarthritis and rheumatoid arthritis. Accumulated evidences showed that Wnt/ß-catenin pathway plays a role in the pathogenesis of cartilage damage. In addition, it is experimentally documented that lncRNA (long non-coding RNA) HOTAIR plays a key role in the regulation of Wnt/ß-catenin pathway based on directly decreased WIF-1 expression. Further, it is reported that Wnt/ß-catenin pathway is a potent pathway to regulate the expression of MMP-13, which is responsible for degradation of collagen type II in articular cartilage. It is increasingly recognized that systems modeling approach provides an opportunity to understand the complex relationships and direct quantitative analysis of dynamic network in various diseases. RESULTS: A dynamic network of lncRNA HOTAIR-mediated Wnt/ß-catenin pathway regulating MMP-13 is developed to investigate the dynamic mechanism of the network involved in the pathogenesis of cartilage damage. Based on the network modeling, the potential therapeutic intervention point Axin is predicted and confirmed by the experimental validation. CONCLUSIONS: Our study provides a promising strategy for revealing potential dynamic mechanism and assessing potential targets which contribute to the prevention of the pathological conditions related to cartilage damage.

The autoantibody response to cyclic citrullinated collagen type II peptides in rheumatoid arthritis.

OBJECTIVES: The detection of anti-citrullinated peptide antibodies (ACPAs) is a serological hallmark of RA. Autoantibodies reactive with collagen type II (CII) are present in RA sera and synovial fluid and are potentially pathogenic. Here, we investigate the prevalence and specificity of the autoantibody responses to defined citrullinated cyclic peptides derived from CII in a China RA cohort. METHODS: Using bead-based multiplex assay, we examined the presence of autoantibodies binding to 54 cyclic 17-mer citrullinated CII peptides, encompassing all citrullinate epitopes in CII, and the corresponding unmodified peptides in 415 RA patients, in addition to 304 patients with OA. Furthermore, the autoantibody responses to a selected set of 10 cyclic citrullinated peptides were also examined in 203 healthy individuals. RESULTS: Autoantibody responses to cyclic citrullinated CII peptides were higher in RA patients as compared with OA patients or healthy individuals, whereas little or negligible antibody responses to cyclic unmodified CII peptides were observed. Interestingly, several novel citrullinated CII epitopes were identified. Antibodies to these novel citrullinated CII epitopes showed not only substantial overlapping reactivities but also had unique specificities. CONCLUSION: We found a high prevalence of autoantibodies against cyclic citrullinated CII in the sera of patients in a China RA cohort. The present study revealed heterogeneous binding patterns against novel citrullinated CII epitopes, which may help to stratify RA patients into different subgroups.

Clinical Effect and Prognosis of Off-Pump Minimally Invasive Direct Coronary Artery Bypass.

BACKGROUND Coronary artery bypass grafting (CABG) is a common procedure to circumvent the obstruction of coronary arteries when stents are unsuitable. CABG is a very traumatic surgery that requires redirecting blood flow to an external pump. Thus, this procedure has many risks during and after surgery, and minimizing these risks would greatly benefit the patients. MATERIAL AND METHODS We selected 126 patients with coronary artery syndrome and who were unsuitable for stent percutaneous coronary intervention. The observation group received minimally invasive direct coronary artery bypass (MIDCAB), while the control group was treated with off-pump CABG. RESULTS Blood markers and echocardiography before and after treatment improved equally in both groups. Neither group exhibited obvious adverse reactions, or liver and kidney function damage. However, surgical bleeding and postoperative observation days were significantly reduced in the MIDCAB group. Death and cardiac shock at the end of follow-up were significantly lower in the MIDCAB group. CONCLUSIONS Overall, the clinical benefits of MIDCAB and OP-CABG were similar, but MIDCAB significantly reduced postoperative hospital stay and intraoperative blood transfusion, and improved clinical prognosis.

Cyr61 participates in the pathogenesis of rheumatoid arthritis via promoting MMP-3 expression by fibroblast-like synoviocytes.

OBJECTIVES: The aim of this study was to investigate the effect and potential mechanism of Cysteine-rich 61 (Cyr61) on stimulating MMP-3 expression by fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients. METHODS: Primarily cultured RA FLS were treated with exogenous Cyr61 protein or Cyr61-siRNA, then, MMP-3 expression was analyzed by real-time PCR, western blotting and ELISA. Signal transduction pathways in Cyr61-induced MMP-3 production were examined by real-time PCR, western blotting, confocal microscopy, luciferase reporter assay. Mice with collagen-induced arthritis (CIA) were treated with anti-Cyr61 monoclonal antibodies (mAb), or IgG1 as control and MMP-3 in the joint was detected by IHC, real-time PCR and western blotting. RESULTS: High expressed MMP-3 and Cyr61 were positively correlated in RA ST; Cyr61 stimulated MMP-3 production in FLS of RA patients in an IL-1ß and TNF-α independent manner. Cyr61 induced MMP-3 could further enhance the invasive ability of RA FLS. Mechanistically, we found that Cyr61 promoted MMP-3 production via the P38, JNK-dependent AP-1 signaling pathway. Blockage of Cyr61 function with monoclonal antibody could decrease MMP-3 expression in the joints of CIA mice. CONCLUSION: This study provides new evidence that Cyr61 participates in RA pathogenesis not only as a pro-inflammatory factor but also plays a key role in bone erosion via promoting MMP-3 expression. We suggest that targeting of Cyr61 may represent a potential strategy in RA treatment.

Molecular Insight into Gut Microbiota and Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic, inflammatory, and autoimmune disorder. Gut microbiota play an important role in the etiology of RA. With the considerable progress made in next-generation sequencing techniques, the identified gut microbiota difference between RA patients and healthy individuals provides an updated overview of the association between gut microbiota and RA. We reviewed the reported correlation and underlying molecular mechanisms among gut microbiota, the immune system, and RA. It has become known that gut microbiota contribute to the pathogenesis of RA via multiple molecular mechanisms. The progressive understanding of the dynamic interaction between gut microbiota and their host will help in establishing a highly individualized management for each RA patient, and achieve a better efficacy in clinical practice, or even discovering new drugs for RA.

Nujiangexathone A, a Novel Compound Derived from Garcinia nujiangensis, Induces Caspase-Dependent Apoptosis in Cervical Cancer through the ROS/JNK Pathway.

Nujiangexathone A (NJXA), a novel compound derived from Garcinia nujiangensis, has been demonstrated to inhibit the proliferation of several human cancer cell lines. This study is the first to demonstrate the apoptosis inductive activities of NJXA and the possible underlying mechanisms. Our results demonstrated that NJXA inhibited colony formation by HeLa and SiHa cells in a dose-dependent manner. An Annexin V-FITC/PI staining assay showed that NJXA strongly triggered apoptosis in a dose-dependent manner. Western blotting analyses showed that NJXA induced the caspase-dependent apoptosis of HeLa and SiHa cells by triggering a series of events, including changes in the levels of Bcl-2 family proteins, cytochrome c release, caspase-3 activation, and chromosome fragmentation. Furthermore, we demonstrated that NJXA induced cell apoptosis by activating the reactive oxygen species (ROS)-mediated JNK signaling pathway. Consistent with this finding, a ROS scavenger, N-acetyl-l-cysteine (NAC, 10 mM), hindered NJXA-induced apoptosis and attenuated the sensitivity of HeLa and SiHa cells to NJXA. In vivo results further confirmed that the tumor inhibitory effect of NJXA was partially through the induction of apoptosis. Taken together, our results demonstrated that NJXA induced the apoptosis of HeLa and SiHa cells through the ROS/JNK signaling pathway, indicating that NJXA could be important candidate for the clinical treatment of cervical cancer.

Cyr61 participates in the pathogenesis of rheumatoid arthritis by promoting proIL-1ß production by fibroblast-like synoviocytes through an AKT-dependent NF-κB signaling pathway.

IL-1ß plays a major role in the development of rheumatoid arthritis (RA). We previously showed that Cyr61 participates in RA pathogenesis as a proinflammatory factor. Here, we found that the levels of IL-1ß and Cyr61 were higher in RA SF than in osteoarthritis (OA) SF. IL-1ß mRNA and proIL-1ß protein levels were remarkably increased in Cyr61-stimulated FLS; however, IL-1ß was hardly detectable in the supernatant. We also found that the level of adenosine triphosphate (ATP) in SF and ST was significantly increased in RA patients and that the level of IL-1ß in supernatants from Cyr61-activated FLS increased significantly when we added exogenous ATP to the culture. Mechanistically, Cyr61 induced proIL-1ß production in FLS via the AKT-dependent NF-κB signaling pathway, and ATP caused Cyr61-induced proIL-1ß to generate IL-1ß in a caspase-1-dependent manner. Our results reveal a novel role of Cyr61 in RA that involves the promotion of proIL-1ß production in FLS.

Exogenous IFN-beta regulates the RANKL-c-Fos-IFN-beta signaling pathway in the collagen antibody-induced arthritis model.

BACKGROUND: Although a variety of drugs have been used to treat the symptoms of rheumatoid arthritis (RA), none of them are able to cure the disease. Interferon ß (IFN-ß) has pleiotropic effects on RA, but whether it can be used to treat RA remains globally controversial. Thus, in this study we tested the effects of IFN-ß on RA patients and on collagen antibody-induced arthritis (CAIA) model mice. METHODS: The cytokine and auto-antibody expression profiles in the serum and synovial fluid (SF) from RA patients were assessed using enzyme-linked immunosorbent assay (ELISA) and compared with the results from osteoarthritis (OA) patients. Exogenous IFN-ß was administered to RA patients and CAIA model mice, and the therapeutic effects were evaluated. Endogenous IFN-ß expression in the joint bones of CAIA model mice was evaluated by quantitative real-time PCR (qRT-PCR). The effects of exogenous IFN-ß on CAIA model mice were assessed using a clinical scoring system, hematoxylin eosin and safranin-O with fast green counterstain histology, molybdenum target X-ray, and tartrate-resistant acid phosphatase (TRAP) staining. The RANKL-RANK signaling pathway was analyzed using qRT-PCR. The RAW 264.7 cell line was differentiated into osteoclasts with RANKL stimulation and then treated with exogenous IFN-ß. RESULTS: The expression of inflammatory cytokines (IFN-γ, IL-17, MMP-3, and RANKL) and auto-antibodies (CII antibodies, RF-IgM, and anti-CCP/GPI) were significantly higher in RA compared with OA patients. After IFN-ß intervention, some clinical symptoms in RA patients were partially alleviated, and the expression of IFN-γ, IL-17, MMP-3, and OPG) returned to normal levels. In the CAIA model, the expression of endogenous IFN-ß in the joint bones was decreased. After IFN-ß administration, the arthritis scores were decreased; synovial inflammation, cartilage, and bone destruction were clearly attenuated; and the expression of c-Fos and NFATc1 were reduced, while RANKL and TRAF6 expression was unchanged. In addition, exogenous IFN-ß directly inhibited RANKL-induced osteoclastogenesis. CONCLUSIONS: Exogenous IFN-ß administration immunomodulates CAIA, may reduce joint inflammation and, perhaps more importantly, bone destruction by inhibiting the RANKL-c-Fos signaling pathway. Exogenous IFN-ß intervention should be selectively used on RA patients because it may only be useful for RA patients with low endogenous IFN-ß expression.

Cyr61 induces IL-6 production by fibroblast-like synoviocytes promoting Th17 differentiation in rheumatoid arthritis.

Cysteine-rich protein 61 (Cyr61)/CCN1 is a product of an immediate early gene and functions in mediating cell adhesion and inducing cell migration. We previously showed that increased production of Cyr61 by fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) promotes FLS proliferation and participates in RA pathogenesis with the IL-17-dependent pathway. However, whether Cyr61 in turn regulates Th17 cell differentiation and further enhances inflammation of RA remained unknown. In the current study, we explored the potential role of Cyr61 as a proinflammatory factor in RA pathogenesis. We found that Cyr61 treatment dramatically induced IL-6 production in FLS isolated from RA patients. Moreover, IL-6 production was attenuated by Cyr61 knockdown in FLS. Mechanistically, we showed that Cyr61 activated IL-6 production via the αvß5/Akt/NF-κB signaling pathway. Further, using a coculture system consisting of purified CD4(+) T cells and RA FLS, we found that RA FLS stimulated Th17 differentiation, and the pro-Th17 differentiation effect of RA FLS can be attenuated or stimulated by Cyr61 RNA interference or addition of exogenous Cyr61, respectively. Finally, using the collagen-induced arthritis animal model, we showed that treatment with the anti-Cyr61 mAb led to reduction of IL-6 levels, decrease of Th17 response, and attenuation of inflammation and disease progression in vivo. Taken together, our results reveal a novel role of Cyr61 in promoting Th17 development in RA via upregulation of IL-6 production by FLS, thus adding a new layer into the functional interplay between FLS and Th17 in RA pathogenesis. Our study also suggests that targeting of Cyr61 may represent a novel strategy in RA treatment.

A novel diagnostic model based on lncRNA PTPRE expression, neutrophil count and red blood cell distribution width for diagnosis of seronegative rheumatoid arthritis.

Diagnosis of seronegative rheumatoid arthritis (SNRA) is difficult due to the lack of diagnostic markers. The study aims to construct a novel diagnostic model based on long noncoding RNAs (lncRNAs) expression and laboratory indicators to provide a new idea for diagnostic methods of SNRA. Differentially expressed lncRNAs in peripheral blood cells of RA patients were screened through eukaryotic long noncoding RNA sequencing and validated by quantitative real-time PCR. Meanwhile, the correlation between lncRNAs expression and laboratory indicators was analyzed. The diagnostic value was evaluated by receiver operating characteristic curve analysis. Finally, combined with laboratory indicators, a diagnostic model for SNRA was constructed based on logistic regression and visualized by nomogram. Expression of ADGRE5, FAM157A, PTPN6 and PTPRE in peripheral blood was significantly increased in RA than healthy donors. Meanwhile, we analyzed the relationship between lncRNAs and erythrocyte sedimentation rate, C-reactive protein and CD4 + T cell-related cytokines and transcription factors. Results showed that FAM157A and PTPN6 were positively related to RORγt, and negatively related to GATA3. Moreover, PTPRE has potential discrimination ability between SNRA and healthy donor (AUC = 0.6709). Finally, we constructed a diagnostic model based on PTPRE, neutrophil count and red blood cell distribution width (RDW). The AUC of the model was 0.939 and well-fitted calibration curves. Decision curve analysis indicated the model had better predict performance in SNRA diagnosis. Our study constructed a novel diagnostic model based on PTPRE, neutrophil count and RDW which may serve as a potential tool for the diagnosis of SNRA.

Limbic system plasticity after electroacupuncture intervention in knee osteoarthritis rats.

Knee osteoarthritis (KOA) is characterized by debilitating pain. Electroacupuncture (EA), a traditional Chinese medical therapy, has shown promise in KOA pain management. This study investigated the therapeutic potential of EA in KOA and its impact on limbic system neural plasticity. Sixteen rats were randomly assigned into two groups: EA group and sham-EA group. EA or sham-EA interventions were administered at acupoints ST32 (Futu) and ST36 (Zusanli) for three weeks. Post-intervention resting-state fMRI was scanned, assessing parameters including Amplitude of low frequency fluctuations (ALFF), regional homogeneity (ReHo), functional connectivity (FC) and nodal characterizations of network within limbic system. The results showed that EA was strategically directed towards the limbic system, resulting in discernible alterations in neural activity, FC, and network characteristics. Our findings demonstrate that EA had a significant impact on the limbic system neural plasticity in rats with KOA, presenting a novel nonpharmacological approach for KOA treatment.

Application of 3D bioprinting technology apply to assessing Dangguiniantongtang (DGNT) decoctions in arthritis.

The aim of this study was to develop a three-dimensional (3D) cell model in order to evaluate the effectiveness of a traditional Chinese medicine decoction in the treatment of arthritis. Chondrocytes (ATDC5) and osteoblasts (MC3T3-E1) were 3D printed separately using methacryloyl gelatin (GelMA) hydrogel bioinks to mimic the natural 3D cell environment. Both cell types showed good biocompatibility in GelMA. Lipopolysaccharide (LPS) was added to the cell models to create inflammation models, which resulted in increased expression of inflammatory factors IL-1ß, TNF-α, iNOS, and IL-6, and decreased expression of cell functional genes such as Collagen II (COLII), transcription factor SOX-9 (Sox9), Aggrecan, alkaline phosphatase (ALP), RUNX family transcription factor 2 (Runx2), Collagen I (COLI), Osteopontin (OPN), and bone morphogenetic protein-2 (BMP-2). The created inflammation model was then used to evaluate the effectiveness of Dangguiniantongtang (DGNT) decoctions. The results showed that DGNT reduced the expression of inflammatory factors and increased the expression of functional genes in the cell model. In summary, this study established a 3D cell model to assess the effectiveness of traditional Chinese medicine (TCM) decoctions, characterized the gene expression profile of the inflammatory state model, and provided a practical reference for future research on TCM efficacy evaluation for arthritis treatment.

Hemisphere lateralization of graph theoretical network in end-stage knee osteoarthritis patients.

Hemisphere functional lateralization is a prominent feature of the human brain. However, it is not known whether hemispheric lateralization features are altered in end-stage knee osteoarthritis (esKOA). In this study, we performed resting-state functional magnetic imaging on 46 esKOA patients and 31 healthy controls (HCs) and compared with the global and inter-hemisphere network to clarify the hemispheric functional network lateralization characteristics of patients. A correlation analysis was performed to explore the relationship between the inter-hemispheric network parameters and clinical features of patients. The node attributes were analyzed to explore the factors changing in the hemisphere network function lateralization in patients. We found that patients and HCs exhibited "small-world" brain network topology. Clustering coefficient increased in patients compared with that in HCs. The hemisphere difference in inter-hemispheric parameters including assortativity, global efficiency, local efficiency, clustering coefficients, small-worldness, and shortest path length. The pain course and intensity of esKOA were positively correlated with the right hemispheric lateralization in local efficiency, clustering coefficients, and the small-worldness, respectively. The significant alterations of several nodal properties were demonstrated within group in pain-cognition, pain-emotion, and pain regulation circuits. The abnormal lateralization inter-hemisphere network may be caused by the destruction of regional network properties.