Systemic inflammation response index as an emerging biomarker in osteoarthritis patients: a bibliometric and large sample retrospective investigation.

OBJECTIVES: To determine the value of the whole-blood inflammatory response index as an emerging biomarker for the assessment of disease activity in osteoarthritis (OA). METHODS: Extensive analysis of the literature on OA and whole-blood inflammatory indicators were provided through a bibliometric approach. Clinical characteristics and indicators of OA patients and healthy controls (HC) were retrospectively analysed. Four whole-blood inflammatory response indices - neutrophil/lymphocyte count (NLR), platelet/lymphocyte count (PLR), monocyte/lymphocyte count (MLR), and systemic inflammation response index (SIRI), as well as clinical traits like the OA patient's self-perception and immune-inflammatory indicators were analysed for correlations. Cut-off values were determined using receiver operating characteristic (ROC) curves, and they were subsequently employed in logistic regression models to work out whole-blood inflammatory indices and disease activity. RESULTS: The pathophysiology of osteoarthritis has received most of the spotlight in literature studies of OA and whole-blood inflammation indicators. The "inflammation", "osteoarthritis" and "disease activity" were the top 3 key word clusters. Retrospective analysis showed that MLR, NLR, PLR, and SIRI were markedly higher in OA subjects compared to HC subjects. ROC curve consequences manifested that SIRI and NLR could separate OA from healthy controls. NLR, PLR, MLR, and SIRI proved to be related to immune-inflammatory markers, visual analogue scale (VAS) scores, and short-form (SF)-36 scores with regard to correlation analysis and association criteria. Logistic regression manifested that SIRI, NLR, and C-reactive protein (CRP) forecasted disease activity, however, the model that combined SIRI and CRP was superior to CRP alone. CONCLUSIONS: SIRI may serve as a non-invasive, appropriate biomarker to correlate with disease activity.

[Identification of Osteoarthritis Inflamm-Aging Biomarkers by Integrating Bioinformatic Analysis and Machine Learning Strategies and the Clinical Validation]. / ç”Ÿç‰©ä¿¡æ¯å­¦å’Œæœºå™¨å­¦ä¹ ç­–ç•¥è¯†åˆ«éª¨å ³èŠ‚ç‚Žç‚Žæ€§è¡°è€ç”Ÿç‰©æ ‡å¿—ç‰©ä¸Žä¸´åºŠéªŒè¯.

Objective: To identify inflamm-aging related biomarkers in osteoarthritis (OA). Methods: Microarray gene profiles of young and aging OA patients were obtained from the Gene Expression Omnibus (GEO) database and aging-related genes (ARGs) were obtained from the Human Aging Genome Resource (HAGR) database. The differentially expressed genes of young OA and older OA patients were screened and then intersected with ARGs to obtain the aging-related genes of OA. Enrichment analysis was performed to reveal the potential mechanisms of aging-related markers in OA. Three machine learning methods were used to identify core senescence markers of OA and the receiver operating characteristic (ROC) curve was used to assess their diagnostic performance. Peripheral blood mononuclear cells were collected from clinical OA patients to verify the expression of senescence-associated secretory phenotype (SASP) factors and senescence markers. Results: A total of 45 senescence-related markers were obtained, which were mainly involved in the regulation of cellular senescence, the cell cycle, inflammatory response, etc. Through the screening with the three machine learning methods, 5 core senescence biomarkers, including FOXO3, MCL1, SIRT3, STAG1, and S100A13, were obtained. A total of 20 cases of normal controls and 40 cases of OA patients, including 20 cases in the young patient group and 20 in the elderly patient group, were enrolled. Compared with those of the young patient group, C-reactive protein (CRP), interleukin (IL)-6, and IL-1ß levels increased and IL-4 levels decreased in the elderly OA patient group (P<0.01); FOXO3, MCL1, and SIRT3 mRNA expression decreased and STAG1 and S100A13 mRNA expression increased (P<0.01). Pearson correlation analysis demonstrated that the selected markers were associated with some indicators, including erythrocyte sedimentation rate (ESR), IL-1ß, IL-4, CRP, and IL-6. The area under the ROC curve of the 5 core aging genes was always greater than 0.8 and the C-index of the calibration curve in the nomogram prediction model was 0.755, which suggested the good calibration ability of the model. Conclusion: FOXO3, MCL1, SIRT3, STAG1, and S100A13 may serve as novel diagnostic biomolecular markers and potential therapeutic targets for OA inflamm-aging.

ASPM promotes migration and invasion of anaplastic thyroid carcinoma by stabilizing KIF11.

Abnormal spindle-like microcephaly-associated (ASPM) protein is crucial to the mitotic spindle function during cell replication and tumor progression in multiple tumor types. However, the effect of ASPM in anaplastic thyroid carcinoma (ATC) has not yet been understood. The present study is to elucidate the function of ASPM in the migration and invasion of ATC. ASPM expression is incrementally upregulated in ATC tissues and cell lines. Knockout (KO) of ASPM pronouncedly attenuates the migration and invasion of ATC cells. ASPM KO significantly reduces the transcript levels of Vimentin, N-cadherin, and Snail and increases E-cadherin and Occludin, thereby inhibiting epithelial-to-mesenchymal transition (EMT). Mechanistically, ASPM regulates the movement of ATC cells by inhibiting the ubiquitin degradation of KIF11 and thus stabilizing it via direct binding to it. Moreover, xenograft tumors in nude mice proved that KO of ASPM could ameliorate tumorigenesis and tumor growth accompanied by a decreased protein expression of KIF11 and an inhibition of EMT. In conclusion, ASPM is a potentially useful therapeutic target for ATC. Our results also reveal a novel mechanism by which ASPM inhibits the ubiquitin process in KIF11.

Phase Conductance of BiFeO3 Film.

In this work, the local conductance of the tetragonal-like (T-like) and rhombohedral-like (R-like) phases of epitaxial BiFeO3 film is systematically studied via conductive atomic force microscopy. At higher tip voltage, there is a mutual transition between the T-like and R-like phases, which could be attributed to the strain relaxation in the T-like phase induced by electric poling, as well as local polarization switching. The T-like phase exhibits a higher conductance, which is related to the lower interface potential barrier between the tip and film surface. Reversible low- and high-current states in the T-like phase can be tuned by polarization switching. These results will be helpful for designing novel nanoelectronic devices, such as voltage and strain sensors.

A Flexible Magnetic Field Sensor Based on PZT/CFO Bilayer via van der Waals Oxide Heteroepitaxy.

Magnetoelectric (ME) magnetic field sensors utilize ME effects in ferroelectric ferromagnetic layered heterostructures to convert magnetic signals into electrical signals. However, the substrate clamping effect greatly limits the design and fabrication of ME composites with high ME coefficients. To reduce the clamping effect and improve the ME response, a flexible ME sensor based on PbZr0.2Ti0.8O3 (PZT)/CoFe2O4 (CFO) ME bilayered heterostructure was deposited on mica substrates via van der Waals oxide heteroepitaxy. A saturated magnetization of 114.5 emu/cm3 was observed in the bilayers. The flexible sensor exhibited a strong ME coefficient of 6.12 V/cm·Oe. The local ME coupling has been confirmed by the evolution of the ferroelectric domain under applied magnetic fields. The flexible ME sensor possessed a stable response with high sensitivity to both AC and DC weak magnetic fields. A high linearity of 0.9988 and sensitivity of 72.65 mV/Oe of the ME sensor were obtained under flat states. The ME output and limit-of-detection under different bending states showed an inferior trend as the bending radius increased. A flexible proximity sensor has been demonstrated, indicating a promising avenue for wearable device applications and significantly broadening the potential application of the flexible ME magnetic field sensors.

[Identification of Characteristic lncRNA Molecular Markers in Osteoarthritis by Integrating GEO Database and Machine Learning Strategies and Experimental Validation].

Objective: To screen for long non-coding RNA (lncRNA) molecular markers characteristic of osteoarthritis (OA) by utilizing the Gene Expression Omnibus (GEO) database combined with machine learning. Methods: The samples of 185 OA patients and 76 healthy individuals as normal controls were included in the study. GEO datasets were screened for differentially expressed lncRNAs. Three algorithms, the least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE), and random forest (RF), were used to screen for candidate lncRNA models and receiver operating characteristic (ROC) curves were plotted to evaluate the models. We collected the peripheral blood samples of 30 clinical OA patients and 15 health controls and measured the immunoinflammatory indicators. RT-PCR was performed for quantitative analysis of the expression of lncRNA molecular markers in peripheral blood mononuclear cells (PBMC). Pearson analysis was performed to examine the correlation between lncRNA and indicators for inflammation of the immune system. Results: A total of 14 key markers were identified with LASSO, 6 genes were identified with SVM-RFE, and 24 genes were identified with RF. Venn diagram was used to screen for overlapping genes identified with the three algorithms, showing HOTAIR, H19, MIR155 HG, and NKILA to be the overlapping genes. The ROC curves showed that these four lncRNAs all had an area under the curve ( AUC) greater than 0.7. The RT-PCR findings revealed relatively elevated expression of HOTAIR, H19, and MIR155HG and decreased expression of NKILA in the PBMC of OA patients compared with those of the normal group ( P<0.01). The results were consistent with the bioinformatics predictions. Pearson analysis showed that the candidate lncRNAs were correlated with clinical indicators for inflammation. Conclusion: HOTAIR, H19, MIR155 HG, and NKILA can be used as molecular markers for the clinical diagnosis of OA and are correlate with clinical indicators of inflammation of the immune system.

Study of the Growth Mechanism of Solution-Synthesized Symmetric Tellurium Nanoflakes at Atomic Resolution.

As a new member of 2D materials, 2D tellurium (Te) has recently attracted much attention due to its intriguing properties. Through hydrothermal processing, 2D Te with tunable thickness and size has been realized, and its growth mechanism has also been studied. However, the tailored growth of 2D Te nanoflakes with symmetrical morphologies and interfacial moiré fringes has never been reported. Here, 2D Te nanoflakes have been prepared using the hydrothermal method, and mirror-symmetrical shapes (including "V-shape," "heart-shape," and "paper airplane-shape") with obvious moiré fringes in the middle of the nanoflakes are observed. Comprehensive transmission electron microscopy (TEM) techniques are utilized for structural characterization of these nanoflakes, especially the moiré fringes in the symmetry axis region of the nanoflakes. The systematic analyses of the moiré fringes and the observation of obvious overlapping edges of the composing nanoflakes from the cross-sectional samples reveal the possible mechanism of morphological evolution for these symmetrical nanoflakes. These details may fill the research gap in the controllable growth of 2D Te nanomaterials, pave the way for the fabrication of 2D Te moiré superlattices and in-plane homojunctions, and promote their future versatile applications.

180° Ferroelectric Stripe Nanodomains in BiFeO3 Thin Films.

There is growing evidence that domain walls in ferroics can possess emergent properties that are absent in the bulk. For example, 180° ferroelectric domain walls in the ferroelectric-antiferromagnetic BiFeO3 are particularly interesting because they have been predicted to possess a range of intriguing behaviors, including electronic conduction and enhanced magnetization. To date, however, ordered arrays of such domain structures have not been reported. Here, we report the observation of 180° stripe nanodomains in (110)-oriented BiFeO3 thin films grown on orthorhombic GdScO3 (010)O substrates and their impact on exchange coupling to metallic ferromagnets. Nanoscale ferroelectric 180° stripe domains with {112̅} domain walls were observed in films <32 nm thick. With increasing film thickness, we observed a domain structure crossover from the depolarization field-driven 180° stripe nanodomains to 71° ferroelastic domains determined by the elastic energy. These 180° domain walls (which are typically cylindrical or meandering in nature due to a lack of strong anisotropy associated with the energy of such walls) are found to be highly ordered. Additional studies of Co0.9Fe0.1/BiFeO3 heterostructures reveal exchange bias and exchange enhancement in heterostructures based on BiFeO3 with 180° domain walls and an absence of exchange bias in heterostructures based on BiFeO3 with 71° domain walls; suggesting that the 180° domain walls could be the possible source for pinned uncompensated spins that give rise to exchange bias. This is further confirmed by X-ray circular magnetic dichroism studies, which demonstrate that films with predominantly 180° domain walls have larger magnetization than those with primarily 71° domain walls. Our results could be useful to extract the structure of domain walls and to explore domain wall functionalities in BiFeO3.

[Exploration of the mechanism of xinfeng capsule in the treatment of ankylosing spondylitis based on B and T lymphocyte attenuator and oxidative stress].

OBJECTIVE: To explore changes of B and T lymphocyte attenuator (BTLA), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAOC), reactive oxygen species (ROS), reactive nitrogen species (RNS), malondialdehyde (MDA) in ankylosing spondylitis (AS) patients, and the effect of Xinfeng Capsule (XFC) on them. METHODS: Totally 120 AS patients were assigned to two groups according to random digit table method, the XFC group (3 XFC pills each time, 3 times a day) and the SASP group (4 SASP tablets each time, twice a day), 60 in each group. All patients were treated for 3 months. Another 60 healthy subjects were recruited as a healthy control group. The expression frequency and activation levels of BTLA were detected using flow cytometry. Serum oxidative stress indices (such as SOD and CAT, TAOC, ROS, RNS, MDA) and contents of cytokines [tumor necrosis factor α (TNF-α), IL-1ß, IL-4, and IL-10] were detected using enzyme-linked immunoassay (ELISA). Erythrocyte sedimentation rate (ESR) was detected using Westergren method. High-sensitivity C-reactive protein (Hs-CRP) was detected using HITACHI 7060 type automatic biochemical analyzer. Clinical efficacies of ASAS 20 and BASDAI50 were assessed using VAS. Correlation analysis between scoring for quality of life and BTLA expression frequency was performed. RESULTS: (1) Clinical efficacies of ASAS 20 and BASDAI50 were significantly better in the XFC group than in the SASP group (P < 0.01). (2) Compared with the healthy control group, BTLA expressions in the peripheral blood of AS patients decreased significantly (P <0. 05); SOD, CAT, and TAOC values significantly decreased (P < 0.01, P < 0.05); ROS, RNS, and MDA values significantly increased (P < 0.01, P < 0.05); TNF-α, IL-1ß, ESR, and Hs-CRP values significantly increased (P < 0.01); IL-4 and IL-10 values decreased significantly (P < 0.01, P < 0.05). (3) Compared with pre-treatment in the same group, BTLA/CD19 + B, BTLA/CD24 + B, SOD, TAOC, IL-4, SF-36 [physical functioning (PF), social functioning (SF), role limitation due to physical problems (RP), role limitation due to emotional problems (RE), body pain (BP), mental health (MH), vitality (VT), general health (GH)] were significantly elevated; ROS, MDA, TNF-α, ESR, Hs- CRP, VAS, BASDAI and BASFI, BAS-G were significantly lower in the peripheral blood of the two groups after treatment (P < 0.01, P < 0.05). Better effect was shown in the XFC group in elevating BTLA/CD19+ B, BTLA/CD24 + B, SOD, TAOC, IL-10, BP, MH, VT, and SF; and lowering ROS, IL-1ß, MDA, TNF-α, ESR, Hs-CRP, VAS, BASDAI, BASFI, and BAS-G (P < 0.01, P < 0.05). (4) Pearson correlation analysis showed, BTLA/CD19 + B expression of the peripheral blood was positively correlated with SOD, CAT, TAOC, IL-4, IL-10, GH, RP, BP, and SF (r = 0.431, 0.325, 0.318, 0.316, 0.348, 0.314, 0.358, 0.318, 0.326, respectively, P < 0.05, P < 0.01), while it was negative correlated with ROS, MDA, TNF-α, IL-1ß, ESR, VAS, and BASDAI (r = -0.342, -0.368, -0.334, -0.354, -0.324, -0.372, -0.342, respectively, P < 0.05, P < 0.01). BTLA/CD24 B expression of the peripheral blood was positively correlated with SOD, TAOC, IL-4, IL-10, GH, RP, BP, SF, RE, MH, VT (r = 0.358, 0.352, 0.372, 0.436, 0.435, 0.326, 0.352, 0.345, 0.326, 0.343, 0.332, respectively, P < 0.05, P < 0.01), while it was negative correlated with ROS, RNS, MDA, ESR, Hs-CRP, VAS, BASDAI, and BASFI (r = -0.447, -0.336, -0.405, -0. 395, -0. 358, -0.436, -0.338, -0.425, respectively, P < 0.05, P < 0.01). CONCLUSION: XFC could improve BTLA expression in the peripheral blood of AS patients, negatively regulate activation and proliferation of B cells, and reduce abnormal immune responses and oxidative stress injury, thereby effectively alleviating joint stiffness and pain.

Xinfeng capsule improves pulmonary function in ankylosing spondylitis patients via NF-ΚB-iNOS-NO signaling pathway.

OBJECTIVE: To study changes in the nuclear factor-κB p65 (NF-κB p65)-inducible nitric oxide synthase (iNOS)-nitric oxide (NO) signaling pathway and the effects of Xinfeng capsules (XFC) in patients with ankylosing spondylitis (AS). METHODS: One hundred twenty patients with AS were randomly divided into an XFC group and a Salazopyrin group. Sixty health subjects were included as a normal control group. In the two treatment groups, pulmonary functional parameters, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), maximal voluntary ventilation (MVV), peak expiratory flow (PEF), forced expiratory flow at 25% of forced vital capacity (FEF25), forced expiratory flow at 50% of forced vital capacity (FEF50), and forced expiratory flow at 75% of forced vital capacity (FEF75) were determined. Enzyme linked immunosorbent assays were used for detection of the serum oxidative stress indexes, NF-κB p65, iNOS, NO, reactive oxygen species (ROS), reactive nitrogen species (RNS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), total antioxidative capacity (TAOC) and interleukin-4 (IL-4), IL-10, IL-1ß, and tumor necrosis factor-α (TNF-α) contents. Westergren's method was used for determination of erythrocyte sedimentation rate (ESR). High-sensitivity C-reactive protein (Hs-CRP) was detected with a 7060 full-automatic biochemical analyzer (Hitachi, Japan). RESULTS: The clinical therapeutic effect in the XFC group was significantly superior to that in the Salazopyrin group (P < 0.01). Compared with the normal control group, FEV1, MVV, PEF, FEF50, FEF75, SOD, CAT, TAOC, IL-4, IL-10 were significantly lower, and NF-κB p65, iNOS, NO, ROS, RNS, MDA, IL-1ß, TNF-α, ESR, and Hs-CRP significantly higher in patients with AS (P < 0.01 or P < 0.05). Compared with before treatment, FEV1, MVV, PEF, FEF50, FEF75, SOD, CAT, TAOC, IL-4, and IL-10 were significantly increased, and NF-κB p65, iNOS, NO, ROS, RNS, MDA, IL-1ß, TNF-α, ESR, CRP, visual analog scales (VAS), Bath ankylosing spondylitis disease active index, Bath ankylosing spondylitis functional index, and Bath ankylosing spondylitis global index significantly decreased in the two treatment groups after treatment (P <. 0.01 or P < 0.05), with significant differences between the XFC and Salazopyrin groups (P < 0.01 or P < 0.05). Spearman correlation analysis indicated that FEV1, MWVV, PEF, FEF50, and FEF75 were positively correlated with SOD, CAT, TAOC, IL-4, and IL-10, and were negatively correlated with NF-κB p65, iNOS, NO, ROS, RNS, MDA, IL-13, TNF-α, ESR, and CRP. CONCLUSION: Patients with AS have local pathologic changes in the spinal cord and other joints. They also have decreased pulmonary function, which is negatively correlated with the NF-κB-iNOS-NO signaling pathway, oxidative indexes, and inflammatory factors. XFC improves rigidity and pain in spinal joints and other symptoms, laboratory indexes, and pulmonary function. The mechanism is possibly related to inhibition of the NF-KB-iNOS-NO signaling pathway.

Use of xinfeng capsule to treat abarticular pathologic changes in patients with rheumatoid arthritis.

OBJECTIVE: To observe the influence of Xinfengcapsule (XFC) on abarticular pathologic changes (APCs) and other indices of patients with rheumatoid arthritis (RA) and explore the mechanism of action of XFC in improving such changes. METHODS: Three-hundred RA patients were divided randomly into a treatment group (n = 150) and control group (n = 150). A normal control (NC) group (n = 90) was also created. Changes in cardiac function, pulmonary function, anemia indices and platelet parameters of RA patients were measured. Curative effects of the two groups were compared, and comparison carried out with the NC group. RESULTS: In 300 RA patients, late diastolic peak flow velocity (A peak) was much higher (P < 0.01) and early diastolic peak flow velocity (E peak), E/A, and left ventricular fraction shortening much lower(P < 0.01) than those in the NC group. Vital capacity (VC), forced vital capacity in one second, forced vitalcapacity (FVC), maximal voluntary ventilation (MVV), maximal expiratory flow in 50% of VC (FEF50) and FEF75 were lowered remarkably (P < 0.05 or P < 0.01). Platelet count (PLT), plateletcrit (PCT) and mean platelet volume (MPV) increased markedly (P < 0.05 or P < 0.01), and hemoglobin (Hb) level decreased significantly (P < 0.05). After XFC treatment, the A peak and PLT and PCT were much lower (P < 0.05), and E/A and the number of red blood cells as well as Hb level were much higher (P < 0.05), as were FVC, MVV and FEF50 (P < 0.05 or P < 0.01), in the treatment group than those in the NC group. Total score of pain and swelling in joints, uric-acid level and high-sensitivity C-reactive protein level were much lower, and superoxide dismutase level as well as the number of CD4 + CD25+ regulation T cells (Treg) and CD4+ CD25+ CD127- Treg were much higher (P < 0.05 or P < 0.01) in the treatment group than those in the NC group. CONCLUSION: RA patients with pathologic changes in joints also suffer from lower cardiac and pulmonary functions and from parameters of anemia and platelet factors. XFC can improve the symptoms of RA patients, ameliorate their cardiac and pulmonary functions and reduce the parameters of anemia and platelet factors. XFC lowers the immune inflammatory reaction to improve APCs in RA patients.

Ultrahigh sensitive and rapid-response self-powered flexible pressure sensor based on sandwiched piezoelectric composites.

Flexible sensors and actuators are the basis for realizing the Internet of Everything. This study identifies specific interfacial polarization and filler dispersion challenges in flexible sensors. A novel sandwich-structured flexible sensor with polydimethylsiloxane (PDMS)-filled Nb2CTx as the interlayer and poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)]-filled barium titanate (BTO) as the upper and lower layers was designed and fabricated. The thickness of the interlayer was optimized to be 6.2 µm, resulting in an ultrahigh sensitivity of 16.05 V/N and ultrashort response time of 626 µs. The interlayer achieved an oriented arrangement of the dipoles in the upper and lower piezoelectric films through interfacial polarization, enhancing the piezoelectric output and sensitivity. The proposed mechanism was confirmed by the dielectric properties, local piezoelectric response, cross-sectional potential simulation, and interfacial electrical calculations. Additionally, the sensor effectively distinguishes various body movements, facial micro-expressions, and throat vibrations during vocalization, and can be applied to ultrahigh-sensitive self-powered flexible piezoelectric pressure sensors.

Integrating clinical data mining, network analysis and experimental validation reveal the anti-inflammatory mechanism of Huangqin Qingre Chubi Capsule in rheumatoid arthritis treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Qingre Chubi Capsule (HQC) is a Chinese medicinal compound used for the treatment of damp-heat pattern rheumatism, guided by the traditional Chinese medicine syndrome differentiation practice. HQC has been used in the clinical treatment of rheumatic diseases for more than 20 years with remarkable efficacy. HQC has been experimentally shown to exert anti-arthritic effects via the Wnt signaling pathway. AIM OF THE STUDY: This study used clinical data mining, network analysis, and in vitro and in vivo tests to investigate the anti-arthritic and possible anti-inflammatory mechanism of HQC. Specifically, emphasis was placed on the function of the hsa_circ_0091,685/EIF4A3/IL-17 axis in the anti-inflammatory process. MATERIALS AND METHODS: A random walk model was used to evaluate the effects of HQC on clinical immune inflammatory marker function in patients with RA. Network analysis was used to predict the potential target genes and pathways of HQC. Hematoxylin & eosin, safranin O-fast green and toluidine blue staining, immunohistochemistry, and transmission electron microscopy were performed to evaluate the anti-arthritic effects of HQC in rat models. Cell Counting Kit-8 assay, quantitative real-time polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, and RNA pull-down were used to study the anti-proliferation and anti-inflammatory mechanisms of HQC. RESULTS: Patients with RA who underwent HQC treatment showed a significant reduction in inflammatory response levels, according to retrospective clinical study. Network analysis revealed that HQC potentially targeted genes and pathways related to inflammation, especially IL-6, IL-17, TNF-α, IL-23, and IL-17 signaling pathway. Animal experiments showed that HQC inhibits inflammation through the IL-17 signaling pathway in rat models. Cellular experiments showed that HQC-containing serum inhibited the inflammatory response in patients with RA-FLS or RA by blocking hsa_circ_0091,685 and EIF4A3 expression. CONCLUSION: In RA patients, HQC reduces the inflammatory response. The antiproliferative and anti-inflammatory qualities of HQC are responsible for its therapeutic impact. The suppression of the hsa_circ_0091,685/EIF4A3/IL-17 axis was linked to these favorable outcomes.

Association between traditional Chinese Medicine and osteoarthritis outcome: A 5-year matched cohort study.

Objective: The aim of this study was to investigate the relationship between Traditional Chinese medicine (TCM) and pain reduction, hospital readmission, and joint replacement in patients with osteoarthritis (OA). Chinese herbal medicine (CHM) prescription patterns were further analyzed to confirm the association with prognosis and quality of life in OA patients. Methods: We retrospectively followed 3,850 hospitalized patients with osteoarthritis between January 2018 and December 2022 using the hospital's HIS system. Propensity score matching (PSM) was used for data matching. Cox's proportional risk model was used to assess the impact of various factors on the outcomes of patients with OA, including pain worsening, readmission, and joint replacement. The Kaplan-Meier survival curve was applied to determine the impact of TCM intervention time on patient outcomes. Data mining methods including association rules, cluster analysis, and random walks have been used to assess the efficacy of TCM. Results: The utilization rate of TCM in OA patients was 67.01% (2,511/3,747). After PSM matching, 1,228 TCM non-user patients and 1,228 TCM user patients were eventually included. The outcomes of pain worsening, re-admission rate, and joint replacement rate of the TCM non-user group were observably higher than those of the TCM user group with OA (p < 0.05). Based on the Cox proportional risk model, TCM is an independent protective factor. Compared with non-TCM users, TCM users had 58.4% lower rates of pain, 51.1% lower rates of re-admission, and 42% lower rates of joint replacement. In addition, patients in the high-exposure subgroup (TCM＞24 months) had a markedly lower risk of outcome events than those in the low-exposure subgroup (TCM ≤24 months). Data mining methods have shown that TCM therapy can significantly improve immune-inflammatory indices, VAS scores, and SF-36 scale scores in OA patients. Conclusion: s TCM acts as a protective factor to improve the prognosis of patients with OA, and the benefits of long-term use of herbal medicines are even greater.

The Diagnostic Features of Peripheral Blood Biomarkers in Identifying Osteoarthritis Individuals: Machine Learning Strategies and Clinical Evidence.

BACKGROUND: People with osteoarthritis place a huge burden on society. Early diagnosis is essential to prevent disease progression and to select the best treatment strategy more effectively. In this study, the aim was to examine the diagnostic features and clinical value of peripheral blood biomarkers for osteoarthritis. OBJECTIVE: The goal of this project was to investigate the diagnostic features of peripheral blood and immune cell infiltration in osteoarthritis (OA). METHODS: Two eligible datasets (GSE63359 and GSE48556) were obtained from the GEO database to discern differentially expressed genes (DEGs). The machine learning strategy was employed to filtrate diagnostic biomarkers for OA. Additional verification was implemented by collecting clinical samples of OA. The CIBERSORT website estimated relative subsets of RNA transcripts to evaluate the immune-inflammatory states of OA. The link between specific DEGs and clinical immune-inflammatory markers was found by correlation analysis. RESULTS: Overall, 67 robust DEGs were identified. The nuclear receptor subfamily 2 group C member 2 (NR2C2), transcription factor 4 (TCF4), stromal antigen 1 (STAG1), and interleukin 18 receptor accessory protein (IL18RAP) were identified as effective diagnostic markers of OA in peripheral blood. All four diagnostic markers showed significant increases in expression in OA. Analysis of immune cell infiltration revealed that macrophages are involved in the occurrence of OA. Candidate diagnostic markers were correlated with clinical immune-inflammatory indicators of OA patients. CONCLUSION: We highlight that DEGs associated with immune inflammation (NR2C2, TCF4, STAG1, and IL18RAP) may be potential biomarkers for peripheral blood in OA, which are also associated with clinical immune-inflammatory indicators.

Regulation of autophagy by circular RNAs in rheumatoid arthritis: Potential targets of action.

Previous studies have shown that autophagic pathogenesis of rheumatoid arthritis (RA) is regulated by circular RNAs (circRNAs), which accelerate bone damage by participating in the immune inflammatory response. Therefore, exploring the mechanisms underlying circRNA regulation of autophagy is essential for maintaining homeostasis of the skeletal microenvironment in RA and may improve our understanding of the specific pathways involved in the development of therapeutics. In this review, we discuss autophagic imbalance in RA and the regulatory mechanisms of circRNAs. We also explore possible targets for circRNA regulation of autophagy in RA, which may provide us with improved knowledge regarding the pathogenesis of RA.

Long Noncoding RNA LINC01614 is a Diagnostic and Prognostic Marker for Breast Cancer.

BACKGROUND: The long intergenic non-coding RNA 01614 (LINC01614) is aberrantly expressed in various malignancies, suggesting its role in oncogenesis. However, it has not been well studied in breast cancer. METHODS: The cancer genome atlas databases (TCGA) and public database of breast cancer gene-expression miner (bc-GenExMiner) were utilized to analyze the prognostic role of LINC01614 in breast cancer. Kaplan-Meier, and Cox regression analyses were conducted for survival analysis. Nomograms were built to predict survival. We used deconvolution-based methods, such as TIMER (Tumor Immune Estimation Resource) and CIBERSORT (cell-type identification by estimating relative subsets of RNA transcripts), to explore the relationship between LINC01614 and immune cell characteristics. RESULTS: The very abnormal expression of LINC01614 was found in 14 types of malignancy, including breast cancer. The LINC01614 was significantly overexpressed in human epidermal growth factor receptor 2 (HER2)+, estrogen receptor (ER)+, progesterone receptor (PR)+, and non-triple negative breast cancer (non-TNBC). According to survival analysis, the higher expression of LINC01614 was related with poor survival. The co-expressed genes analysis exhibited that LINC01614 was closely associated with the collagen-associated process and phosphoinositide 3-kinases-protein kinase B (PI3K-Akt) signaling pathway. Moreover, this study has explored the association among LINC01614 expression, tumor-infiltrating immune cells, and the efficacy of chemotherapeutics. CONCLUSIONS: Our data reveal the expression pattern of LINC01614 in breast carcinoma with different molecular subtypes. The results also indicated that the LINC01614 could be a novel diagnostic and prognostic marker for breast carcinoma.

Huangqin Qingre Chubi Capsule is Associated with Reduced Risk of Readmission in Patients with Rheumatoid Arthritis: A Real-World Retrospective Cohort Study.

Purpose: The therapeutic effects of Huangqin Qingre Chubi (HQC) in rheumatoid arthritis (RA) have been documented. However, there is a lack of real-world clinical evidence supporting its efficacy. Methods: Patients diagnosed with RA were recruited from the First Affiliated Hospital of the Anhui University of Chinese Medicine. Patient information was obtained from the hospital's database. Propensity score matching (PSM), Kaplan-Meier curve, and Cox proportional hazards model were used to control confounding factors and analyze the factors influencing readmission. Association rule analysis and random walk evaluation models were used to evaluate the correlations among HQC treatment, inflammation indicators, and self-perception of patients (SPP) scale. Results: After PSM, 3423 patients were enrolled, with 1142 in the HQC group and 2281 in the non-HQC group. The readmission risk of the HQC group was significantly lower than that of the non-HQC group. Combined univariate and multivariate analysis results revealed that risk factors for readmission were age >60 years, female sex, hypertension, chronic gastritis, and elevated levels of laboratory indices, including anticyclic citrullinated peptide and complement component 3 (C3) and C4. HQC, disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs, and glucocorticoid therapy were protective factors for readmission. HQC treatment was closely associated with improvements in many factors, including erythrocyte sedimentation rate, C-reactive protein, C3, rheumatoid factor levels, visual analog scale, depression self-assessment scale, and patient-reported activity index scores with RA. Conclusion: HQC treatment can reduce the risk of readmission and significantly improve immune inflammatory indicators and SPP in patients with RA, with no risk of hepatorenal toxicity.

Caffeic acid phenethyl ester suppresses metastasis of breast cancer cells by inactivating FGFR1 via MD2.

BACKGROUND: Tumor metastasis is the main cause of death for breast cancer patients. Caffeic acid phenethyl ester (CAPE) has strong anti-tumor effects with very low toxicity and may be a potential candidate drug. However, the anti-metastatic effect and molecular mechanism of CAPE on breast cancer need more research. METHODS: MCF-7 and MDA-MB-231 breast cancer cells were used here. Wound healing and Transwell assay were used for migration and invasion detection. Western blot and RT-qPCR were carried out for the epithelial-to-myofibroblast transformation (EMT) process investigation. Western blot and immunofluorescence were performed for fibroblast growth factor receptor1 (FGFR1) phosphorylation and nuclear transfer detection. Co-immunoprecipitation was used for the FGFR1/myeloid differentiation protein2 (MD2) complex investigation. RESULTS: Our results suggested that CAPE blocks the migration, invasion, and EMT process of breast cancer cells. Mechanistically, CAPE inhibits FGFR1 phosphorylation and nuclear transfer while overexpression of FGFR1 reduces the anti-metastasis effect of CAPE. Further, we found that FGFR1 is bound to MD2, and silencing MD2 inhibits FGFR1 phosphorylation and nuclear transfer as well as cell migration and invasion. CONCLUSION: This study illustrated that CAPE restrained FGFR1 activation and nuclear transfer through MD2/FGFR1 complex inhibition and showed good inhibitory effects on the metastasis of breast cancer cells.

Identification and validation of the microRNAs and hub genes for pancreatic ductal adenocarcinoma by an integrated bioinformatic analysis.

Background: In the progression of pancreatic ductal adenocarcinoma (PDAC), aberrant micro RNAs (miRNAs) expression plays a crucial role. This study sought to identify and validate the key miRNAs and potential target genes involved in PDAC. A bioinformatic analysis was conducted to determine their potential use as biomarkers and therapeutic targets. Methods: Gene profiling data sets (GSE41372 and GSE32688) were retrieved from the Gene Expression Omnibus database. Differentially expressed miRNAs (DEMs) with a P value <0.05, and |fold change| >2 was identified. The prognostic value of the DEMs was accessed using the online server Kaplan-Meier plotter. Further, gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using DAVID 6.7. The protein-protein interaction analyses were conducted with STRING, and miRNA-hub gene networks were constructed using Cytoscape software. The PDAC cells were transfected with miRNA inhibitors or mimics. Cell Counting Kit-8 assays and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to examine cell proliferation and apoptosis, respectively. Wound-healing assays were performed to evaluate cell migration. Results: Three DEMs (hsa-miR-21-5p, hsa-miR-135b-5p, and hsa-miR-222-3p) were identified. High expression levels of hsa-miR-21-5p, hsa-miR-135b-5p, or hsa-miR-222-3p predicted poor overall survival in PDAC patients. The pathway analysis revealed that the predicted target genes of the DEMs were closely related to several signaling pathways (including 'pathways in cancer', 'miRNAs in cancer', 'platinum drug resistance', 'lipid and atherosclerosis', and 'MAPK signaling pathway'). The MYC proto-oncogene (MYC), phosphate and tensin homolog gene (PTEN), poly(ADP-ribose) polymerase 1 (PARP1), von Hippel-Lindau (VHL), and fork head box p3 (FOXP3) were identified as potential target genes. The inhibition of hsa-miR-21-5p, hsa-miR-135b-5p, or hsa-miR-222-3p expression decreased cell proliferation. The overexpression of hsa-miR-21-5p, hsa-miR-135b-5p, or hsa-miR-222-3p facilitated PDAC cell migration. Conclusions: This study constructed the miRNA-hub gene network, which provides novel insights into the PDAC progression. Although further research is required, our results offer clues for new potential prognostic markers and therapeutic targets of PDAC.