Patient self-reported experience and satisfaction with golimumab and etanercept treatments for rheumatic diseases: A cohort study.

Golimumab and etanercept both exhibit good efficacy in treating rheumatic diseases, while the patient self-reported measurement of treatment improvement and injection experience lacks sufficient evidence. Hence, this study aimed to compare the satisfaction with disease improvement and injection experience and the level of injection site reactions (ISRs) between golimumab-treated and etanercept-treated patients with rheumatic diseases. A total of 312 patients with rheumatic diseases were serially enrolled. Among them, 158 patients received golimumab (golimumab group); the other 154 patients were treated with etanercept (etanercept group) according to the actual disease status, physician advice, and patient willingness. Satisfaction with disease improvement was assessed using the 7-point Likert scale; satisfaction with injection experience and level of ISRs were both determined by the 5-point Likert scale. Satisfaction degrees with global injection experience (P = .025), injection device (P = .008), injection frequency (P = .010), and injection convenience (P = .003) were superior in the golimumab group to the etanercept group, while satisfaction degrees with global disease improvement, symptom relief, and speed of action did not vary (all P > .050) between the 2 groups. Discomfort (P = .005), swelling (P < .001), pain (P = .028), and burning (P = .035) levels were lower in the golimumab group than in the etanercept group. In addition, among 56 patients with a history of tumor necrosis factor inhibitor treatment before golimumab, 40 (71.4%) patients preferred golimumab to other tumor necrosis factor inhibitor. After switching to golimumab treatment, the level of ISRs in most patients was reduced or comparable. Golimumab achieves a satisfying injection experience and relieves the level of ISRs over etanercept in patients with rheumatic diseases.

Role and Therapeutic Potential for Targeting Fibroblast Growth Factor 10/FGFR1 in Relapsed Rheumatoid Arthritis.

OBJECTIVE: Fibroblast-like synoviocytes (FLSs) contribute to inflammation and joint damage in rheumatoid arthritis (RA). However, the regulatory mechanisms of FLSs in relapse and remission of RA remain unknown. Identifying FLS heterogeneity and their underlying pathogenic roles may lead to discovering novel disease-modifying antirheumatic drugs. METHODS: Combining single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics, we sequenced six matched synovial tissue samples from three patients with relapse RA and three patients in remission. We analyzed the differences in the transcriptomes of the FLS subsets between the relapse and remitted phases. We validated several key signaling pathways using quantitative real-time PCR (qPCR) and multiplex immunohistochemistry (mIHC). We further targeted the critical signals in vitro and in vivo using the collagen-induced arthritis (CIA) model in rats. RESULTS: Lining and sublining FLS subsets were identified using scRNA-seq. Differential analyses indicated that the fibroblast growth factor (FGF) pathway was highly activated in the lining FLSs from patients with relapse RA for which mIHC confirmed the increased expression of FGF10. Although the type I interferon pathway was also activated in the lining FLSs, in vitro stimulation experiment suggested that it was independent of the FGF10 pathway. FGF10 knockdown by small interfering RNA in FLSs significantly reduced the expression of receptor activator of NF-κB ligand. Moreover, recombinant FGF10 protein enhanced bone erosion in the primary human-derived pannus cell culture, whereas the FGF receptor (FGFR) 1 inhibitor attenuated this process. Finally, administering an FGFR1 inhibitor displayed a therapeutic effect in a CIA rat model. CONCLUSION: The FGF pathway is a critical signaling pathway in relapse RA. Targeted tissue-specific inhibition of FGF10/FGFR1 may provide new opportunities to treat patients with relapse RA.

Spatiotemporal mode-locking and dissipative solitons in multimode fiber lasers.

Multimode fiber (MMF) lasers are emerging as a remarkable testbed to study nonlinear spatiotemporal physics with potential applications spanning from high energy pulse generation, precision measurement to nonlinear microscopy. The underlying mechanism for the generation of ultrashort pulses, which can be understood as a spatiotempoal dissipative soliton (STDS), in the nonlinear multimode resonators is the spatiotemporal mode-locking (STML) with simultaneous synchronization of temporal and spatial modes. In this review, we first introduce the general principles of STML, with an emphasize on the STML dynamics with large intermode dispersion. Then, we present the recent progress of STML, including measurement techniques for STML, exotic nonlinear dynamics of STDS, and mode field engineering in MMF lasers. We conclude by outlining some perspectives that may advance STML in the near future.

The effect of JuanBiQiangGu granules in combination with methotrexate on joint inflammation in rheumatoid arthritis: a randomized controlled trial.

Background: Rheumatoid arthritis (RA) joint inflammation severely affects joint function and quality of life in patients and leads to joint deformities and limb disability. The non-steroidal anti-inflammatory drugs used in the treatment of RA do not fully control the progression of joint inflammation and bone destruction and have notable adverse reactions. Traditional Chinese medicine formula JuanBiQiangGu Granules (JBQG) are commonly used for the treatment of RA inflammation and delay of bone destruction, but has not been evaluated through high-quality clinical studies. There is a pressing need for well-designed, randomized, parallel, controlled clinical studies to evaluate the exact effect of JBQG on RA joint inflammation and improvement of patient quality of life. Methods: This is a randomized, parallel, controlled clinical study in which 144 patients with rheumatoid arthritis who met the inclusion criteria were randomly assigned to 2 groups in a 1:1 ratio. The JBQG group received methotrexate 7.5 mg qw and JBQG granules 8 mg tid, while the MTX group received methotrexate 7.5 mg qw. The endpoint was 12 weeks after treatment. Relevant indices at baseline, 4 weeks, 8 weeks, and 12 weeks after treatment were observed and recorded, and DAS28-ESR, HAQ-DI, and Sharp scores were recorded for each patient. Blood samples were collected to test for CRP, ESR, TNF-α, IL-1ß, IL-6, IL-17, and INF-γ, and adverse reactions and liver and kidney function (AST, ALT, Cr, BUN) were recorded for safety assessment. After 12 weeks of treatment, the effect of JBQG granules on disease activity, improvement in bone damage, and patient quality of life scores and safety in RA patients were evaluated. Results: A total of 144 subjects completed treatment (71 in the JBQG group and 73 in the MTX group) and were included in the analysis. At baseline, there were no significant differences between the groups in terms of the observed indicators (p > 0.05). After treatment, 76.06% of patients in the JBQG group had DAS28-ESR levels below or equal to Low, including 45.07% in Remission and 5.63% in High, compared to 53.1% in the MTX group below or equal to Low, 12.33% in Remission, and 17.81% in High. CRP was significantly reduced (8.54 ± 5.87 vs. 11.86 ± 7.92, p < 0.05, p = 0.005), ESR was significantly reduced (15.1 ± 6.11 vs. 21.96 ± 9.19, p < 0.0001), TNF-α was significantly reduced (1.44 ± 0.83 vs. 1.85 ± 1.07, p < 0.05, p = 0.011), IL-17 was significantly reduced (0.53 ± 0.33 vs. 0.71 ± 0.38, p < 0.05, p = 0.004), and INF-γ was significantly reduced (3.2 ± 1.51 vs. 3.89 ± 1.77, p < 0.05, p = 0.014). The median (IQR) OPG in the JBQG group was 2.54 (2.21-3.01), significantly higher than in the MTX group 2.06 (1.81-2.32), p < 0.0001), and the median (IQR) ß-CTX in the JBQG group was 0.4 (0.32-0.43), significantly lower than in the MTX group 0.55 (0.47-0.67), p < 0.0001). The median (IQR) VSA scores were 2 (1-3), a decrease from 3 (2-4) in the MTX group (p < 0.0001). The median (IQR) Sharp scores were 1 (1-2), a decrease from 2 (1-2) in the MTX group, but the difference was not statistically significant (p > 0.05, p = 0.28). The median (IQR) HAQ-DI scores were 11 (8-16), significantly lower than in the MTX group 26 (16-30) (p < 0.0001). The median (IQR) AST in the JBQG group was 16 (12-20), with a significant difference compared to the MTX group 19 (13-25) (p < 0.01, p = 0.004); the median (IQR) ALT in the JBQG group was 14 (10-18), with a significant difference compared to the MTX group 16 (11-22.5) (p < 0.05, p = 0.015). There were no statistically significant differences in Cr or BUN (p > 0.05). Conclusion: JuanBiQiangGu Granules can be used to treat patients with rheumatoid arthritis, alleviate joint inflammation, reduce the incidence of adverse reactions to methotrexate, and has good safety. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/index.html; identifier: ChiCTR2100046373.

Electroacupuncture alleviates pain after total knee arthroplasty through regulating neuroplasticity: A resting-state functional magnetic resonance imaging study.

INTRODUCTION: We aimed to evaluate the efficacy of electroacupuncture in relieving acute pain after total knee arthroplasty (TKA) and related mechanism. METHODS: In this randomized, single-blind, and sham-acupuncture controlled study. Forty patients with postoperative acute pain were recruited and randomly divided electroacupuncture group (n = 20) and sham-acupuncture group (n = 20) from November 2020 to October 2021. All patients received electroacupuncture or sham-acupuncture for 5 days after TKA. Their brain regions were scanned with resting-state functional magnetic resonance imaging before and after intervention. Pain was scaled. Another 40 matched healthy controls underwent scanning once. The amplitude of low-frequency fluctuation (ALFF) values was compared. Pearson's correlation analysis was utilized to explore the correlation of ALFF with clinical variables in patients after intervention. RESULTS: Compared with the HCs, patients with acute pain following TKA had significantly decreased ALFF value in right middle frontal gyrus, right supplementary motor area, bilateral precuneus, right calcarine fissure and surrounding cortex, and left triangular part of inferior frontal gyrus (false discovery rate corrected p < .05). Patients had higher ALFF value in bilateral precuneus, right cuneus, right angular gyrus, bilateral middle occipital gyrus, and left middle temporal gyrus after electroacupuncture (AlphaSim corrected p < .01). Correlation analysis revealed that the change (postoperative day 7 to postoperative day 3) of ALFF in bilateral precuneus were negatively correlated with the change of NRS scores (r = -0.706; p = .002; 95% CI = -0.890 to -0.323) in EA group. CONCLUSIONS: The functional activities of related brain regions decreased in patients with acute pain after TKA. The enhancement of the functional activity of precuneus may be the neurobiological mechanism of electroacupuncture in treating pain following TKA.

Self-starting spatiotemporal mode-locking using Mamyshev regenerators.

Bridging multi-mode fibers and Mamyshev regenerators holds promise for pulse energy scaling in fiber lasers. However, initialization of a multi-mode Mamyshev oscillator remains a practical challenge. Here we report self-starting spatiotemporal mode-locking (STML) in a multi-mode Mamyshev oscillator without active assistance. The first initialized mode-locking is unstable, but stable STML can be attained by increasing the filter separation. Simulations verify the capability of reaching self-starting STML using Mamyshev regenerators and unveil the effect of filter separation on the self-starting ability.

Expanded CD1c+CD163+ DC3 Population in Synovial Tissues Is Associated with Disease Progression of Osteoarthritis.

The mechanisms underlying osteoarthritis (OA) have recently been hypothesized to involve a dysfunctional immune system. In this study, we collected synovium, synovial fluid (SF), and peripheral blood from 21 patients. Mononuclear cells were characterized using FCM. H&E staining and mIHC histological assessment of synovium were performed. Cytokine levels in the SF were measured using ELISA. We observed similar frequencies of immune cells in the synovium and SF, which were enriched in DCs. Notably, CD1c+CD163+ DC3s were expanded in the synovium and SF. Furthermore, we found that DC3s were primarily located within the ectopic lymphoid-like structure (ELLS) in close proximity to CD8+ T cells. Finally, the level of TNF-α and IL12p70 in the SF correlated with the severity of OA. These data suggest that OA is an immune system-related disease and that DC3s may play an active role in OA progression by promoting ELLS formation and inflammatory responses.

Cerebral mechanism of opposing needling for managing acute pain after unilateral total knee arthroplasty: study protocol for a randomized, sham-controlled clinical trial.

BACKGROUND: Opposing needling is a unique method used in acupuncture therapy to relieve pain, acting on the side contralateral to the pain. Although opposing needling has been used to treat pain in various diseases, it is not clear how opposing needling affects the activity of the central nervous system to relieve acute pain. We herein present the protocol for a randomized sham-controlled clinical trial aiming to explore the cerebral mechanism of opposing needling for managing acute pain after unilateral total knee arthroplasty (TKA). METHODS: This is a randomized sham-controlled single-blind clinical trial. Patients will be allocated randomly to two parallel groups (A: opposing electroacupuncture group; B: sham opposing electroacupuncture group). The Yinlingquan (SP9), Yanglingquan (GB34), Futu (ST32), and Zusanli (ST36) acupoints will be used as the opposing needling sites in both groups. In group A, the healthy lower limbs will receive electroacupuncture, while in group B, the healthy lower limbs will receive sham electroacupuncture. At 72 h after unilateral TKA, patients in both groups will begin treatment once per day for 3 days. Functional magnetic resonance imaging will be performed on all patients before the intervention, after unilateral TKA, and at the end of the intervention to detect changes in brain activity. Changes in pressure pain thresholds will be used as the main outcome for the improvement of knee joint pain. Secondary outcome indicators will include the visual analogue scale (including pain during rest and activity) and a 4-m walking test. Surface electromyography, additional analgesia use, the self-rating anxiety scale, and the self-rating depression scale will be used as additional outcome indices. DISCUSSION: The results will reveal the influence of opposing needling on cerebral activity in patients with acute pain after unilateral TKA and the possible relationship between cerebral activity changes and improvement of clinical variables, which may indicate the central mechanism of opposing needling in managing acute pain after unilateral TKA. TRIAL REGISTRATION: Study on the brain central mechanism of opposing needling analgesia after total kneearthroplasty based on multimodal MRI ChiCTR2100042429 . Registered on January 21, 2021.

Risk factors of cervical cancer among ethnic minorities in Yunnan Province, China: a case-control study.

BACKGROUND: Cervical cancer is a common malignant tumor of the female reproductive system in the world, which is a serious threat to women's life and health. According to the latest report, the incidence of cervical cancer is 11.42 per 100 000, and the mortality rate is 3.77 per 100 000 in Yunnan Province, which is still higher than the national average. Although there have been some relevant studies on the risk factors of cervical cancer in recent years, research on ethnic minorities is lacking in Yunnan Province. OBJECTIVE: To analyze and explore the related risk factors of cervical cancer in women of ethnic minorities in Yunnan Province, to provide the scientific basis for the development of cervical cancer prevention and control strategies and measures in this region. METHODS: In total 1119 cervical cancer patients diagnosed by histopathology at the Yunnan Cancer Center (Yunnan Cancer Hospital) from January 2010 to December 2019 were selected as the case group. According to the 1:1 matching principle of the case-control study, 1119 patients with nonmalignant tumors of the same nationality, the same hospital, age difference less than 3 years old, were selected as the control group. Univariate and multivariate conditional logistic regression were used for statistical analysis. RESULTS: Basic medical insurance for rural residents (OR = 3.659; P = 0.003), human papilloma virus (HPV) infection (OR = 90.030; P < 0.001) and concurrent reproductive tract infections (OR = 1.992; P = 0.047) were risk factors for cervical cancer. Late first marriage(OR = 0.881; P = 0.032), the number of normal childbirths ≤2 (OR = 0.480, P = 0.033) and contraception (OR = 0.291; P = 0.002) were positive factors for cervical cancer. CONCLUSION: The high incidence of cervical cancer in Yunnan minority women is the result of many factors: HPV infection is the highest risk factor for cervical cancer, women with reproductive tract infections and basic medical insurance for rural residents have a higher risk for cervical cancer; Late first marriage, the number of deliveries ≤2 and contraception are positive factors for cervical cancer.

Microbial inoculations improved rice yields by altering the presence of soil rare bacteria.

Microbial inoculation is a promising way to improve crop yields in an eco-friendly and economic manner. However, the effects of inoculation on soil resident rare species, representing most of the diversity, are still not well documented and need further assessment. Here, we conducted a pot experiment to test the effects of single-strain and co-inoculants of Rhodopseudomonas palustris and Bacillus subtilis on soil rare and abundant bacteria through sequencing 16S ribosomal RNA gene amplicons. The results showed that microbial inoculations significantly improved the rice yields up to 17.73 %, and R. palustris and B. subtilis co-inoculation showed synergistic effects on rice yields. The inoculations exerted significant modification in soil bacterial community structure, with a more pronounced influence on the rare community than the abundant. The large shifts in rare community structure induced the increase of beneficial rare members and enhanced the membrane transporters and signal transduction together with the increase of some essential metabolism pathways. According to the random forest modeling, relative abundance of the subgroups of rare and abundant communities could explain 61.37-63.09 % of the variations in the rice yields. Structural equation modeling further demonstrated the potential predominant role of rare bacteria in impacting the crop yields (r = 0.95). Overall, our study proved the effectiveness of the co-inoculant in promoting the rice yields through mediating the soil rare bacteria of microbial community. These findings expand current understanding of the microbial inoculation impacts on subsequent crop yield and the underlying microbial mechanisms in agricultural ecosystem.

Altered brain activity in end-stage knee osteoarthritis revealed by resting-state functional magnetic resonance imaging.

INTRODUCTION: Knee osteoarthritis (KOA) is characterized by a degenerative change of knee cartilage and secondary bone hyperplasia, resulting in pain, stiffness, and abnormal walking gait. Long-term chronic pain causes considerable cortical plasticity alternations in patients. However, the brain structural and functional alterations associated with the pathological changes in knee joints of end-stage KOA patients remain unclear. This study aimed to analyze the structural and functional connectivity alterations in end-stage KOA to comprehensively understand the main brain-associated mechanisms underlying its development and progression. METHODS: In this study, 37 patients with KOA and 37 demographically matched healthy controls (HCs) were enrolled. Alternations in gray matter (GM) volume in patients with KOA were determined using voxel-based morphometry. The region with the largest GM volume alteration was selected as the region of interest to calculate the voxel-wise resting-state functional connectivity (rs-FC) in the two groups. Pearson's correlation coefficient was used to analyze the correlation between clinical measures and GM volume alternations in patients with KOA. RESULTS: Compared with HCs, patients with KOAs exhibited significantly decreased GM volumes in the left middle temporal gyrus (left-MTG) and the left inferior temporal gyrus. Results of the voxel-wise rs-FC analysis revealed that compared with HCs, patients with KOA had decreased left-MTG rs-FC to the right dorsolateral superior frontal gyrus, left middle frontal gyrus, and left medial superior frontal gyrus. GM volume in the left-MTG was negatively correlated with the Western Ontario and McMaster Universities Arthritis Index in patients with KOA (r = -0.393, p = .016). CONCLUSION: Structural remodeling and functional connectivity alterations may be one of the central brain mechanisms associated with end-stage KOA.

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 ).

Vector quartic solitons in birefringent fibers.

We theoretically investigated the vector properties of quartic solitons in a pure fourth-order-dispersion birefringent fiber and a quartic-dispersion-dominant mode-locked fiber laser. We found that, compared with scalar pure quartic solitons, a vector quartic soliton (VQS) in the birefringent fiber still preserves the Gaussian shape, except for the distinctions of reduced peak power, central frequency offset, slight frequency chirp, and mitigated oscillatory tails. We also demonstrated that pulse shaping in the mode-locked laser cavity could explicitly facilitate the formation of Kelly sidebands and distortion of oscillatory tails. Furthermore, dynamical evolutions of quartic group-velocity-locked and polarization-rotating vector solitons were obtained to enrich the nonlinear community of VQSs. We believe that our elaborate findings will bring insights into both the fundamental understanding and potential applications of VQSs.

Effect of Multiple Doses of Intravenous Tranexamic Acid on Perioperative Blood Loss in Total Knee Arthroplasty: A Randomized Controlled Study.

OBJECTIVE: To identify the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) following primary total knee arthroplasty (TKA) with a tourniquet. METHODS: This is a single-blind randomized controlled study that recruited osteoarthritis patients who had undergone primary unilateral TKA from May 2019 to May 2020 at our medical center. A total of 300 patients were randomly divided into three groups to receive: one dose (1 g) of IV-TXA before skin incision combined with one dose (1.5 g) of intra-articular tranexamic acid（IA-TXA) followed by a single dose of IV-TXA (1 g) for 3 h (group A); two doses of IV-TXA (1 g) for 3 and 6 h (group B); or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group C) postoperatively. TKA with a tourniquet was performed by the same surgical team. The primary outcomes were total blood cell loss (TBL), hidden blood loss (HBL), maximum hemoglobin (Hb) drop, and transfusion rate. Secondary outcomes were levels of C-reactive protein (CRP) and D-dimer, and the incidence of postoperative complications. One-way analysis of variance, subgroup analysis, and multivariate correlation analysis were used to calculate the differences among the three groups. RESULTS: The study included 56 male and 244 female patients aged 60-80 years. The mean TBL, the mean HBL, and the maximum Hb drop in group C (471.2 ± 190.6 mL, 428.4 ± 190.3 mL, and 21.2 ± 3.8 g/L, respectively) were significantly lower than those in groups B (563.4 ± 224.6 mL, P = 0.030; 519.9 ± 226.4 mL, P = 0.033; and 23.2 ± 4.1 g/L, P = 0.001, respectively), and A (651.6 ± 254.1 mL, P < 0.001; 607.1 ± 254.3 mL, P < 0.001; and 25.1 ± 4.3 g/L, P < 0.001, respectively). No transfusions were required. The postoperative acute inflammatory reaction was less problematic for patients in Group C, and the incidence of thromboembolic events was similar among the groups (P > 0.05). In addition, there were positive correlations between the HBL and the tourniquet inflation time (r = 0.844, P < 0.001). Similarly, the level of CRP on POD1 (r = 0.393, P < 0.001) and POD3 (r = 0.149, P = 0.010), and the level of D-dimer on POD1 (r = 0.382, P < 0.001) were positively correlated with the HBL. CONCLUSION: Three doses of postoperative IV-TXA decreased blood loss and diminished the postoperative inflammatory and fibrinolytic response more than a single dose or two doses in elderly patients following TKA without increasing the incidence of adverse events.

Multiple-dose tranexamic acid for perioperative blood loss in total knee arthroplasty in patients with rheumatoid arthritis：a single-blinded, randomised, parallel-controlled study protocol in China.

INTRODUCTION: This clinical trial is designed to evaluate the effect of multiple-dose tranexamic acid (TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA). METHODS AND ANALYSIS: A randomised, single-blinded, parallel-controlled study will be designed. Patients with RA (age 50-75 years) undergoing unilateral primary end-stage total knee arthroplasty will be randomly divided into group A or group B. Group A will be treated with one dose of TXA (1 g; intravenous injection 3 hours postsurgery) and group B with three doses (1 g; intravenous injection at 3, 6 and 12 hours postsurgery) after surgery. The primary outcomes will be evaluated with blood loss, maximum haemoglobin drop and transfusion rate. The secondary outcomes will be evaluated with knee function and complications. ETHICS AND DISSEMINATION: The Shanghai Guanghua Hospital of Integrated Traditional Chinese Medicine and Western Medicine Ethics Committee approved in this study in July 2019. Informed consent will be obtained from all participants. Results of the trial will be published in the Dryad and repository in a peer-reviewed journal. Additionally, deidentified data collected and analysed for this study will be available for review from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: ChiCTR1900025013.

Using electroacupuncture to recover muscle strength in patients with knee osteoarthritis after total knee arthroplasty: a study protocol for a double-blinded, randomized, and placebo-controlled trial.

BACKGROUND: Total knee arthroplasty (TKA) is a gold standard for patients with terminal term gonarthrosis for reducing pain, correcting deformities, and regaining stability. However, post-TKA muscle strength recovery is often difficult. Although electroacupuncture (EA) enhances lower extremity muscle strength of the lower extremity, there is limited evidence regarding its effect on lower extremity muscle strength in post-TKA patients. Consequently, this trial intends to evaluate the efficacy of post-TKA EA on the recovery of lower extremity muscle strength, specifically, during the early post-TKA period. METHODS/DESIGN: This is a double-blinded, randomized, and controlled trial. It will be conducted between August 2020 and December 2020. Ninety-four participants with KOA who have undergone unilateral TKA will be randomized into a treatment (EA) group and a control (sham EA) group. The former and latter groups will receive EA and sham EA, respectively, at ST37, ST36, SP10, and SP9 acupoints. The participants will undergo ten treatment sessions over 2 weeks (5 sessions per week). The primary outcomes will include changes in muscle strength and the Hospital for Special Surgery score at the second week from baseline (pre-op 1 day or POD 3). The secondary outcomes will include a 4-m walk test, numerical rating scale score, the Hamilton Anxiety Scale score, and additional analgesia use. Additional outcomes will include the incidence of analgesia-related side effects and the participant satisfaction rate. Participant blinding will also be assessed where they will be asked to guess whether they received EA after the latest intervention. Adverse EA events will be documented and assessed throughout the trial. DISCUSSION: EA is helpful for post-TKA recovery and enhancement of lower limb muscle strength. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027806 . Registered on 29 November 2019.

Buildup dynamics of asynchronous vector solitons in a polarization-multiplexed dual-comb fiber laser.

Polarization-multiplexed dual-comb fiber lasers enable significant applications in dual-comb spectroscopy and optical sensing. However, the complexity of the underlying formation dynamics of dual-comb solitons has not been unveiled so far. Here, we capture the real-time spectral evolutions of both vector solitons from the initial fluctuations, with the help of the time-stretch dispersive Fourier transform technique. Both vector solitons experience the relaxation oscillation, quasi-mode-locking, beating dynamics, and mode locking, accompanying central wavelength shifts in opposite directions, which might be induced by the gain saturation during their buildup processes. Moreover, polarization-dependent gain in the gain fiber leads to the different buildup time of both vector solitons. Our findings open new perspectives for dual-comb buildup dynamics and might impact laser design for applications.

Downregulation of lncRNA ITSN1-2 correlates with decreased disease risk and activity of rheumatoid arthritis (RA), and reduces RA fibroblast-like synoviocytes proliferation and inflammation via inhibiting NOD2/RIP2 signaling pathway.

This study aimed to investigate the effect of lnc-ITSN1-2 knockdown on cell proliferation, apoptosis, inflammation and mRNA expression patterns in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), and the correlation of its synovium tissue expression with disease risk, inflammatory cytokines and disease activity of RA. Control shRNA plasmids and lnc-ITSN1-2 shRNA plasmids were transfected into RA FLS, and then cell proliferation, apoptosis, inflammatory cytokines expressions were evaluated. Subsequently, mRNA sequencing and bioinformatics analyses were conducted, and rescue experiment of nucleotide-binding oligomerization domain 2 (NOD2) mRNA overexpression on alleviating the functions of lnc-ITSN1-2 was performed. Additionally, lnc-ITSN1-2 and NOD2 mRNA expressions in synovial tissue in 30 RA patients and 15 controls were measured. Lnc-ITSN1-2 expression was increased in RA FLS compared with normal FLS. Lnc-ITSN1-2 knockdown inhibited RA FLS proliferation and inflammation while promoted RA FLS apoptosis. mRNA sequencing and bioinformatics analyses revealed 144 upregulated and 98 downregulated genes by lnc-ITSN1-2 knockdown, which were enriched in regulating inflammatory responses and cytokines related pathways. NOD2 was selected for rescue experiment, which disclosed that upregulating NOD2 alleviated the effect of lnc-ITSN1-2 knockdown on cell proliferation, apoptosis and inflammation in RA FLS. In addition, synovial tissue lnc-ITSN1-2 positively associated with NOD2 mRNA, and both of them positively correlated with disease risk, inflammation and activity of RA. Downregulation of lnc-ITSN1-2 correlates with decreased disease risk and activity of RA, and reduces RA FLS proliferation and inflammation via regulating NOD2/RIP2 signaling pathway.

Circulating lnc-ITSN1-2 expression presents a high value in diagnosis of rheumatoid arthritis and correlates with disease activity.

This study was aimed to investigate the correlation of lnc-ITSN1-2, lnc-APOC3-2 and lnc-AL355149.1 expressions in plasma by qPCR with rheumatoid arthritis (RA) risk and disease activity. 30 RA patients and 30 health controls (HC) were enrolled in this study. Plasma sample were collected from RA patients before any treatment carried out and HCs. Top 3 RA related long non-coding RNAs (lncRNAs) (lnc-ITSN1-2, lnc-APOC3-2 and lnc-AL355149.1) were selected by a computational framework prediction. The expression of lnc-ITSN1-2, lnc-APOC3-2 and lnc-AL355149.1 were determined by qPCR method. Age (P=0.350) and gender (P=0.542) were similar between RA patients and HCs. lnc-ITSN1-2 level was extremely increased in RA patients compared with HCs (P<0.001), while both lnc-APOC3-2 and lnc-AL355149.1 expressions were numerically higher in RA patients but with no statistical significance (P=0.152 and P=0.139 respectively). Receiver Operating Characteristic (ROC) curves were performed and we found lnc-ITSN1-2 disclosed a great diagnostic value for RA with area under curve (AUC) 0.898, 95% CI 0.813-0.983, and sensitivity was 90.0% and specificity was 80.0% respectively at the best cut-off point. In addition, plasma lnc-ITSN1-2 level was illuminated to be positively associated with erythrocyte sedimentation rate (ESR) (P=0.049), C-reactive protein (CRP) (P<0.001) and disease activity score in 28 joints (DAS28) (P=0.007). Circulating lnc-ITSN1-2 expression was observed to be a novel and convincing biomarker for RA diagnosis as well as disease management.

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.