Infrared laser moxibustion for cancer-related fatigue in breast cancer survivors: a randomized controlled trial.

BACKGROUND: Cancer-related fatigue (CRF) is a pervasive, persistent, and distressing symptom experienced by cancer patients, for which few treatments are available. We investigated the efficacy and safety of infrared laser moxibustion (ILM) for improving fatigue in breast cancer survivors. METHODS: A three-arm, randomized, sham-controlled clinical trial (6-week intervention plus 12-week observational follow-up) was conducted at a tertiary hospital in Shanghai, China. The female breast cancer survivors with moderate to severe fatigue were randomized 2:2:1 to ILM (n = 56) sham ILM (n = 56), and Waitlist control (WLC)(n = 28) groups. Patients in the ILM and sham ILM (SILM) groups received real or sham ILM treatment, 2 sessions per week for 6 weeks, for a total of 12 sessions. The primary outcome was change in the Brief Fatigue Inventory (BFI) score from baseline to week 6 with follow-up until week 18 assessed in the intention-to-treat population. RESULTS: Between June 2018 and July 2021, 273 patients were assessed for eligibility, and 140 patients were finally enrolled and included in the intention-to-treat analysis. Compared with WLC, ILM reduced the average BFI score by 0.9 points (95% CI, 0.3 to 1.6, P = .007) from baseline to week 6, with a difference between the groups of 1.1 points (95% CI, 0.4 to 1.8, P = .002) at week 18. Compared with SILM, ILM treatment resulted in a non-significant reduction in the BFI score (0.4; 95% CI, -0.2 to 0.9, P = .206) from baseline to week 6, while the between-group difference was significant at week 18 (0.7; 95% CI, 0.2 to 1.3, P = .014). No serious adverse events were reported. CONCLUSION: While ILM was found to be safe and to significantly reduce fatigue compared with WLC, its promising efficacy against the sham control needs to be verified in future adequately powered trials. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04144309. Registered 12 June 2018.

The characteristics of registered acupuncture clinical trials enrolling cancer patients.

PURPOSE: This study sought to explore and summarize the global state of acupuncture clinical trials enrolling cancer patients included in international registries to date. METHODS: All relevant trials evaluating acupuncture-related interventions for the treatment of cancer that were registered in 16 trial registries from January 1, 2001, through December 31, 2020, were identified. Subsequent publications related to these trials were additionally retrieved from the PubMed, Cochrane Library, Embase, CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), and Wanfang databases. We compared information included in these registries regarding completed trials with any associated publications, with a focus on study design, sample size, and selective reporting, based on the registered protocol. RESULTS: In total, 222 eligible trials across 19 countries were identified. These trials included 17 specific cancer types and 32 symptoms. The five most common cancer types were breast cancer, head and neck cancer, colorectal cancer, lung cancer, and gastric cancer, accounting for almost half of all registered trials (48.2%). The top five symptoms included in these trials were chemotherapy-induced peripheral neuropathy (CIPN), cancer-related pain, cancer-related fatigue, chemotherapy-induced nausea and vomiting (CINV), and gastrointestinal dysfunction. The overall rate of article publication was low, with publications being associated with just 33.3% of these registered trials. CONCLUSIONS: This review is the first snapshot of the landscape of acupuncture clinical trials registered in international trial registries, providing a methodological basis for the management of common treatment- and disease-related side effects among cancer patients undergoing acupuncture and offering useful information that will guide future acupuncture-focused research.

A cross-sectional study on the association of anxiety and depression with the disease activity of systemic lupus erythematosus.

BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune disease that affects multiple systems and increases the risk of mental disorders such as depression and anxiety. We conducted an observational, single-center, cross-sectional study to investigate the relationship between depression, anxiety, and SLE disease activity. METHODS: The Patient Health Questionnaire 9 (PHQ-9) was used to assess depression, and the 7-item Generalized Anxiety Disorders Scale was used to assess anxiety (GAD-7). Using the chi-square/exact Fisher's tests, socio-demographic data, clinical and other characteristics of SLE patients were compared between depression or anxiety and non-depression/non-anxiety groups. To identify optimal levels of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) for predicting depression or anxiety, receiver-operator curves (ROC) were drawn. RESULTS: Among the 325 patients involved in this study, patients with depression or anxiety had significantly higher SLE activity (p < 0.001), and more frequent musculoskeletal (p < 0.05) and neuropsychiatric symptoms (p < 0.05). Depression and anxiety are more common in the moderate-severe active group than in the inactive-mild active group (depression: OR 3.350, 95%CI 2.015, 5.570, p < 0.001; anxiety: OR 4.085, 95%CI 2.493, 6.692, p < 0.001). The optimal SLEDAI cutoff value of 8.5 predicted depression with a sensitivity of 50.5% and a specificity of 78.4% (AUC 0.660, p < 0.001) and anxiety with a sensitivity of 54.2% and a specificity of 78.4% (AUC 0.684, p < 0.001). CONCLUSION: SLE disease activity is positively associated with the severity of depression and anxiety. Those patients whose SLEDAI scores are greater than 8.5 are more likely to suffer from mental disorders which require additional attention to them.

Lidocaine Inhibits Hepatocellular Carcinoma Development by Modulating circ_ITCH/miR-421/CPEB3 Axis.

BACKGROUND: Lidocaine plays an anticancer role in hepatocellular carcinoma. Nevertheless, the mechanism of lidocaine in hepatocellular carcinoma remains largely unclear. AIMS: This study aims to assess the function of lidocaine and explore the potential regulatory mechanism. METHODS: Hepatocellular carcinoma cells were challenged via lidocaine. Cell proliferation, apoptosis, migration, and invasion were detected via colony formation, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, flow cytometry, Western blot, and transwell analyses. Circular RNA itchy E3 ubiquitin protein ligase (circ_ITCH), microRNA-421 (miR-421), and cytoplasmic polyadenylation element-binding protein 3 (CPEB3) abundances were detected via quantitative reverse transcription polymerase chain reaction or Western blot. The relationship between miR-421 and circ_ITCH or CPEB3 was tested via dual-luciferase reporter analysis. The role of circ_ITCH in lidocaine-challenged cell growth in vivo was assessed via xenograft model. RESULTS: Lidocaine inhibited hepatocellular carcinoma cell proliferation by decreasing colony formation and cell viability. Lidocaine suppressed hepatocellular carcinoma cell migration and invasion and promoted apoptosis. circ_ITCH and CPEB3 levels were decreased in hepatocellular carcinoma tissues and cells, and were restored in cells via lidocaine treatment. circ_ITCH knockdown weakened the suppressive effect of lidocaine on hepatocellular carcinoma development, which was abolished via CPEB3 overexpression. circ_ITCH could modulate CPEB3 by competitively binding with miR-421. miR-421 knockdown mitigated the effect of circ_ITCH silence in lidocaine-challenged cells. circ_ITCH knockdown increased xenograft tumor growth. CONCLUSIONS: Lidocaine represses hepatocellular carcinoma cell proliferation, migration, and invasion and promotes apoptosis via regulating circ_ITCH/miR-421/CPEB3 axis, indicating a new insight into the mechanism of lidocaine in hepatocellular carcinoma.

[Correlations of Methylenetetrahydrofolate Reductase Gene Polymorphism and Genomic DNA Hypomethylation Level with Ankylosing Spondylitis].

Objective To investigate the relationship of both DNA methylation level and methylenetrahydrofolate reductase(MTHFR)gene polymorphism with ankylosing spondylitis(AS). Methods Totally 200 Chinese AS patients with HLA-B27(+)and 120 healthy controls were included from Hunan Province.All the cases were diagnosed according to the 1984 modified New York criteria for AS.The DNA methylation was examined by cytosine extension method,while the MTHFR gene C677T polymorphism was analyzed by the polymerase chain reaction(PCR)and restriction fragment length polymorphism(RFLP).The plasma homocysteine(Hcy)level was examined by enzyme-linked immunosorbent assay(ELISA),while the red blood folate level was analyzed by the specific immunoassays. Results The ratio of the T/T genotype mutation in the AS group was significantly higher than in the control group(17.0% vs. 5.0%;χ2=9.874, P=0.002).The plasma homocysteine concentration of AS group was(18.71 ± 2.42)µmol/L,which was significantly higher than that in normal control group [(10.97 ± 2.93)µmol/L](t=24.402, P<0.001).The plasma Hcy concentration of the T/T genotype [(21.70±1.80)µmol/L] was significantly higher than that of the C/C genotype[(18.31±1.94)µmol/L](q=12.088, P=0.01)and the C/T genotype [(17.80±2.18)µmol/L](q=6.496, P=0.01)in the AS group.The DNA methylation level of the T/T genotype in AS group was significantly lower than that in normal control group(t=5.655, P<0.001)and also significantly lower than those of the C/C genotype(t=11.514, P<0.001)and the C/T genotype in AS group(t=10.287, P<0.001). Conclusions In the Han population in Hunan Province,the C677T polymorphism of the MTHFR gene is associated with the onset of AS.The T/T mutation at position 677 of the MTHFR gene is an important influencing factor for hyperhcyemia in the AS patients.The T/T mutation at position 677 of the MTHFR gene is associated with genomic DNA hypomethylation.Thus,hypomethylation of DNA may be one of the pathogenic mechanisms of AS.

[High Expression of Multidrug Resistance Gene-1 Can Aggravate Resistance to Methotrexate in Rheumatoid Arthritis Patients].

Objective To explore the role of multidrug resistance gene-1(MDR1)gene in methotrexate(MTX)resistance in patients with rheumatoid arthritis(RA).Methods Fibroblast-like synoviocytes(FLS)from RA patients were infected with recombinant adenovirus Ad-EGFP-MDR1 in vitro to obtain MDR1 over-expressed RA FLS.The transcription level of MDR1 gene and the expression level of its coding product P-glycoprotein(P-gp) rotein were detected by real-time PCR and Western blot analysis.The efflux function was verified by rhodamine 123 efflux assay.The resistance to MTX was detected by MTT assay.Results RA FLS were infected with recombinant adenovirus Ad-EGFP-MDR1;72 hours later,the particles size in MDR1 over-expressed RA FLS increased,the cell volume became larger,and the growth rate decreased.The transcription level of MDR1(1.4325±0.3924 vs.0.0650±0.0070;t=6.035,P=0.004),the expression level of P-gp protein(1.8667±0.2857 vs. 0.9367±0.0551;t=5.536,P=0.005),and the ability of extracellular rhodamine 123(979.43±196.81 vs.1680.06±147.04;t=-4.940,P=0.008) in MDR1 over-expressed RA FLS were significantly higher than those of negative virus control RA-FLS,and the survival rate of MDR1 over-expressed RA FLS was significantly increased at each concentration of MTX(P<0.05).Conclusion The high expression of MDR1 can affect the efflux ability to MTX by up-regulating the expression of P-gp,thus enhancing the drug resistance to MTX in RA FLS.

[Meta Analysis of Risks of Cardiocerebral Vascular Events in Patients with Primary Biliary Cholangitis].

To systematically evaluate the risks of cardiocerebral vascular events in patients with primary biliary cholangitis(PBC). Methods We carried out a Meta analysis by RevMan 5.3 software to investigate literatureon the risk of cardiocerebral vascular events in patients with PBC and controls. Results Compared with non-PBC controls,PBC patients had significantly higher risk of coronary events(RR=1.56,P=0.0002);however,the risk of cerebrovascular events showed no significant difference between these two groups(RR=1.01,P=0.94).Subgroup analysis demonstrated a significantly lower risk of transient ischemic attack or carotid stenosis in PBC patients(RR=0.63,P=0.03);however,there was no significant difference in the risk of stroke(RR=1.11,P=0.40). Conclusion Patients with PBC have an increased risk of coronary events but may have a lower risk of transient ischemic attack or carotid stenosis.

[Clinical effect of tocilizumab on patients with severe active rheumatoid arthritis].

OBJECTIVE: To evaluate therapeutic effects and adverse reactions of tocilizumab on patients with severe active rheumatoid arthritis (RA).
 Methods: Twelve patients with severe refractory RA were treated with tocilizumab. The clinical and laboratory indices and the side effects were recorded after treatment.
 Results: The clinical and laboratory indices and the disease activity score 28 (DAS28) were observed in all patients, which were significantly improved after TCZ therapy (P<0.05), and no obvious adverse reactions were found.
 Conclusion: Tocilizumab can effectively relieve the symptoms and improve the conditions of severe active RA.

Mechanisms of Tripterygium wilfordii Hook F on treating rheumatoid arthritis explored by network pharmacology analysis and molecular docking.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory and disabling disease that imposes significant economic and social costs. Tripterygium wilfordii Hook F (TwHF) has a long history of use in traditional Chinese medicine for treating joint disorders, and it has been shown to be cost-effective in treating RA, but its exact mechanism is unknown. Objective: The goal of the network pharmacology analysis and molecular docking was to investigate the potential active compounds and associated anti-RA mechanisms of TwHF. Methods: TCMSP and UniProt databases were searched for active compounds and related targets of TwHF. PharmGKB, DrugBank, OMIM, TTD, and the Human Gene Databases were used to identify RA-related targets. The intersected RA and TwHF targets were entered into the STRING database to create a protein-protein interaction network. R software was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking technology was used to analyze the optimal effective components from TwHF for docking with the selected target gene. Results: Following screening and duplicate removal, a total of 51 active compounds and 96 potential targets were chosen. The PPI network revealed that the target proteins are CXCL8, CXCL6, STAT3, STAT1, JUN, PPARG, TP53, IL14, MMP9, VEGFA, RELA, CASP3, PTGS2, IFNG, AKT1, FOS, ICAM1, and MAPK14. The results of the GO enrichment analysis focused primarily on the response to lipopolysaccharide, the response to molecules of bacterial origin, and the response to drugs. The KEGG results indicated that the mechanisms were closely related to lipid and atherosclerosis, chemical carcinogenesis-receptor activation, Kaposi sarcoma-associated, herpesvirus infection, hepatitis B, fluid shear stress and atherosclerosis, IL-17 signaling pathways, Th17-cell differentiation, and so on, all of which are involved in angiogenesis, immune cell chemotaxis, and inflammatory responses. Molecular docking results suggested that triptolide was the appropriate PTGS1, PTGS2, and TNF inhibitors. Conclusion: Our findings provide an essential role and basis for further immune inflammatory studies into the molecular mechanisms of TwHF and PTGS1, PTGS2, and TNF inhibitor development in RA.

TPE-embedded butterfly bis-crown ether with controllable conformation and supramolecular chiroptical property.

Understanding how subtle structural differences between macrocyclic conformational isomers impact their properties and separation has garnered increasing attention in the field of supramolecular synthetic chemistry. In this work, a series of tetraphenylene (TPE)-embedded butterfly bis-crown ether macrocycles (BCE[n], n = 4-7), comprising two crown ether side rings and a TPE core, are synthesized through intramolecular McMurry coupling. Unexpectedly, the presence of flexible oligoethylene chains with varying lengths are found to influence molecular conformation via multiple intramolecular interactions, resulting in the formation of two stabilized conformers with specific semi-rigid symmetric/asymmetric structures (sym-BCE[n] and asym-BCE[n], n = 5, 6). Moreover, it is noteworthy that neither symmetric nor asymmetric conformers are present in the more rigid BCE[4] or the more flexible BCE[7]. Interestingly, these conformers display distinct fluorescence properties and host-guest binding abilities, and only sym-BCE[5] can serve as a host for chiral polymer binding, resulting in the formation of chiral supramolecular assemblies through host-guest interaction induced chirality. Moreover, both circular dichroism and circularly polarized luminescence signals of the obtained assemblies can be switched off by the addition of sodium ion, suggesting potential applications in the field of dynamic chiral materials.

[Expression of survivin in rheumatoid arthritis].

OBJECTIVE: To detect the correlation between survivin and rheumatoid arthritis (RA) to determine the possible mechanism of RA and multidrug resistance in refractory rheumatoid arthritis (RRA). METHODS: We collected 15 normal controls, 35 early untreated RA patients, 20 effectively treated RA patients and 25 RRA patients according to selection standard. The expression of survivin in the peripheral blood lymphocytes was detected by immunocytochemical method. RESULTS: There was significant difference in the survivin expression in the peripheral blood lymphocytes between the early untreated and normal control group (χ(2)=29.59, P<0.01). The survivin expression in the peripheral blood lymphocytes of effectively treated RA group slightly elevated, but had no significant difference with the normal control group (χ(2)=1.591, P>0.05). The survivin expression in the peripheral blood lymphocytes of the RRA group was significantly stronger than in the effectively treated RA group (χ(2)=24.35, P<0.01), and normal control group (χ(2)=26.53, P<0.01), with no significant difference compared with early untreated group (χ(2)=0.014,P>0.05). CONCLUSION: Survivin has an influential role in the occurrence and development of rheumatism arthritis. Survivin might be involved in refractory multidrug resistance of RA and be one of the multidrug resistance mechanism of RRA.

[Grey scale and power Doppler ultrasonographic assessment of bone erosion and disease activity in early rheumatoid arthritis].

OBJECTIVE: To evaluate the sensitivity and predictive value of grey scale and power Doppler ultrasound assessment of bone erosionin disease activity in patients with early rheumatoid arthritis (RA). METHODS: Fifty-six patients with early RA underwent blinded sequential clinical, laboratory and ultrasound assessments, and at the same time 20 of these patients underwent X-ray and enhanced MRI. For each patient, 28-joint disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and health assessment questionnaire (HAQ) were recorded. The presence of bone erosion and synovitis was investigated in 28 joints by gray-scale and power Doppler ultrasonography. The ultrasound joint count and index for active synovitis with power Doppler signal were calculated. RESULTS: The number of bone erosions detected by ultrasonography was 5.7 times that of X-ray, while both MRI and ultrasonography were consistent (91.5%). The number of synovitis detected by ultrasonography was 1.6 times as much as by physical examination, and consistent MRI (95.7%). PDUS parameters demonstrated a highly significant correlation with DAS28, ESR and CRP, while a negative correlation with HAQ. CONCLUSION: Grey scale and power Doppler ultrasonography is a sensitive and reliable method to assess bone erosion and inflammatory activity in early RA. PDUS findings may have a predictive value in disease activity.

[Meta analysis of infection risks of anti-TNF-α treatment in rheumatoid arthritis].

OBJECTIVE: To systematically evaluate the risks of anti-TNF-α treatment-associated infection, severe infection and tuberculosis in rheumatoid arthritis (RA) patients, and to reduce the infection incidences associated with anti-TNF-α therapy. METHODS: We used Meta analysis to systematically review randomized controlled trials on anti- TNF-α treatment associated risks of infection, severe infection and tuberculosis in RA patients. RESULTS: Although no statistically significant differences were detected in TB risk between anit- TNF-α treatment and the control group (0.5% vs 0.07%; P=0.27, OR=1.85, 95% CI: 0.62-5.52), there still existed a clinically obvious elevation of TB risk in monoclonal anti-TNF-α treatment, which was illustrated by the results that no TB case was reported in the etanercept group, but 11 TBs in 2050 infliximab-treated cases, and 3 TBs in 722 adalimumab-treated cases. The total infection and severe infection risks were also significantly higher in patients receiving anti-TNF-α treatment (P<0.05). Subanalysis revealed that etanercept showed no significantly higher infection or severe infection risk than control group (P>0.05), while both kinds of monoclonal antibodies of TNF-α blockers showed a significantly elevated infection or severe infection risks (P<0.05). High doses of anti-TNF-α treatment were associated with statistically increased risks of severe infection (6.0% vs 2.8%, P=0.04, OR=1.68, 95% CI: 1.02-2.78). CONCLUSION: The TB risk of anti-TNF-α treatment deserves close attention, especially in places with high rate of BCG vaccination and MTb infection. Monoclonal anti-TNF-α treatment brings higher risks of infection and severe infection than soluble TNF-α receptor.

Effect of Moxibustion Combined With Cisplatin on Tumor Microenvironment Hypoxia and Vascular Normalization in Lewis Lung Cancer Mice.

PURPOSE: This study was developed to evaluate the effects of moxibustion on tumor microenvironmental hypoxia in a murine model of Lewis lung carcinoma (LLC). METHODS: Twenty-four tumor-bearing mice were randomized into tumor group (T), tumor + cisplatin group (TC), tumor + moxibustion group (TM), and tumor + cisplatin + moxibustion group (TMC) (n = 6/group). Six age-matched C57BL/6 mice were employed as control group (Ctrl). A tumor model was established by implanting LLC cells into the right flank of each mouse. Animals in the TM group received moxibustion treatment at the ST36 (bilateral) and GV4 acupoints on the day of visible tumor formation. Moxibustion treatment was performed every other day for a total of 7 sessions. Animals in the TC group were intraperitoneally injected with cisplatin (3 mg/kg) on day 3 after visible tumor formation, and this treatment was performed every 3 days for 4 times. Animals in the TMC group underwent combined moxibustion and chemotherapy treatment, following the same conditions as outlined above. Following treatment, the concentrations of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), CD31, and Ki67 were measured using ELISA, Western blot, and immunohistochemical staining. RESULTS: Compared to the tumor group, treatment in the TM, TC, and TCM groups resulted in varying reductions in tumor growth (P < .001 or P < .05), while tumor microenvironmental hypoxia was alleviated as evidenced by the downregulation of HIF-1α, VEGFA, and CD31(P < .001-P < .05). CONCLUSION: Our results suggest that a combined approach of moxibustion and cisplatin can alleviate intratumoral hypoxia, promote vascular normalization, and slow the growth of LLC tumors in mice.

Association of the MDR1 3435 polymorphism in patients with refractory rheumatoid arthritis in a Chinese population.

To evaluate whether the multidrug resistance gene 1 (MDR1) exon 26 polymorphisms are associated with the refractory rheumatoid arthritis (RRA). The study was carried out on two hundred and twenty-three patients with RA treated and one hundred and three normal controls. The RA treated were divided into two groups according the response to disease-modifying antirheumatic drugs (DMARDs). There were 108 patients in the effective group and 115 patients in the ineffective group. Genotypes of the C3435T polymorphism were determined by polymerase chain reaction followed by restriction digestion (PCR-RFLP). There were significant differences in the genotype frequency and allele frequency among three groups. Compared to responders and controls, the nonresponders carried more CC genotype (χ(2) = 5.306, P = 0.021; χ(2) = 7.810, P = 0.005) and more C allele (χ(2) = 6.601, P = 0.010; χ(2) = 12.172, P = 0.000). But, there were no statistically significant differences in genotype nor allele frequency between RA and healthy controls. The results from our study suggest that the C3435T MDR1 gene polymorphism may not be related with the RA susceptibility, but may influence the efficacy of RA therapy with DMARDs, and the 3435CC genotype may be related with RRA.

Concurrence of malignant fibrohistiocytoma and Takayasu arteritis: a case report.

Takayasu arteritis (TA) is a type of systemic large-vessel vasculitis that usually affects the aorta and its major branches. It remains unrecognized owing to delayed diagnosis (Boltin et al. in Rheumatol Int 27(10):985-987, 2007) and non-characteristic clinical features. It has been described in association with many autoimmune diseases, such as inflammatory digestive tract diseases. However, report of TA associated with tumors, especially malignant tumors, are rare. We here presented a case diagnosed by both Takayasu arteritis and malignant fibrous histiocytoma, from which we learned not only clinical lessons, but also consensus of relationships between these two diseases.

Efficacy and safety of Janus kinase inhibitors in patients with ankylosing spondylitis: A systematic review and meta-analysis.

OBJECTIVES: To assess the efficacy and safety of janus kinase (JAK) inhibitors in the treatment of ankylosing spondylitis (AS). METHODS: We searched the PubMed and Cochrane Central Register of Controlled Trials to Nov 1, 2021. We included all randomized controlled trials (RCTs) evaluating JAK inhibitors in the treatment of AS. Two reviewers independently selected studies, extracted data and assessed the risk of bias. RESULTS: Four RCT studies with 779 participants were included in the meta-analysis. Compared with placebo group, percentages of participants achieving responses of Assessment of spondyloarthritis international society(ASAS) 20, ASAS 40, ASAS 5/6, Bath AS disease activity index (BASDAI) 50 were significantly higher in JAK inhibitor group respectively; changes from baseline in AS disease activity score using C-reactive protein(ASDAS-CRP), Maastricht AS enthesitis score (MASES), AS Quality of Life (ASQoL) score, short-form-36 health survey physical component summary (SF-36 PCS) score, BASDAI, Bath AS functional index (BASFI), Bath AS metrology index (BASMI), Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) score, SPARCC joint score and Work Productivity and Activity Impairment (WPAI) Overall Work Impairment score showed significant improvements in JAK inhibitor group. The incidence of adverse events (AEs) and severe adverse events (SAEs) showed no significant differences between the JAK inhibitor and placebo groups. CONCLUSIONS: JAK inhibitors showed a satisfactory and promising efficacy in the treatment of active AS not only in mitigating disease activity, but also substantially improving patient's physical function, emotional well-being and social participation. The results of this meta-analysis provide solid evidence for JAK inhibitor as a novel therapeutic strategy for patients with active AS.

[Effects of resveratrol on proliferation and apoptosis of TNF-alpha induced rheumatoid arthritis fibroblast-like synoviocytes].

OBJECTIVE: To observe the effect of resveratrol (Res) on in vitro proliferation and apoptosis of TNF-alpha induced rheumatoid arthritis fibroblast-like synoviocytes (RA FLS), and further to investigate the PI3 K/Akt/BAD signal mechanism. METHOD: The inhibition rate of RA FLS was examined by MTT assay. Cell cycle and the amount of apoptotic cells was measured by flow cytometry. PI3K/Akt/BAD signal transduction proteins expression was measured by western blot. RESULT: The living cells measured by MTT dose and time-dependently reduced in Res groups. In Res groups, the fraction of living cells in the S-phase and G2/M-phase decreased respectively, while that in G1-phase increased, the difference was statistically significant compared with the TNF-alpha group (P < 0.05). Flow cytometry demonstrated that the apoptosis rate increased with increased Res concentration. Res inhibited TNF-alpha induced phosphorylation of Akt and BAD in RA FLS. CONCLUSION: Res can inhibit RA FLS proliferation and induce apoptosis through inhibition of PI3K/Akt/BAD signalling pathway. Res may provide a new therapeutic approach in treatment of RA.

Inhibition of miR-16 enhances the sensitivity of fibroblast-like synovial cells to methotrexate by restraining MDR1/P-gp expression via NF-κB pathway.

MicroRNAs (miRNAs) are demonstrated to contribute to the regulation of drug resistance in a number of diseases. Nevertheless, little is known about the role and the underlying mechanism of miR-16 in rheumatoid arthritis (RA) methotrexate resistance. In this study, we firstly examined the miR-16 expression in the serum and synovial fluid from RA patients who were unresponsive to methotrexate monotherapy (UR-MTX patients) and responsive RA patients (R-MTX patients). Secondly, the miR-16 expression was measured in both fibroblast-like synovial cells (FLS) and methotrexate resistance RA-FLS cells (FLS-MTX). FLS cells used in this study were isolated from synovial tissue specimens obtained from patients with RA who underwent total joint replacement. FLS-MTX cells were conducted by gradually increasing the concentration of methotrexate in the medium. The construction of FLS-MTX cells was confirmed by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay. Thirdly, in order to further investigate the role of miR-16 in FLS-MTX cells, we introduced miR-16 inhibitor into FLS-MTX cells to knockdown the expression of miR-16, used fluorescence quantitative PCR to detect the inhibition efficiency. The effects of miR-16 inhibition on cell viability, cell cycle arrest and apoptosis in FLS-MTX cells were monitored with MTT and flow cytometry analysis, respectively. And the regulation of miR-16 on P-glycoprotein (P-gp) was performed using qRT-PCR, western blotting, and immunofluorescence staining. Fourthly, ammonium pyrrolidinedithiocarbamate (PDTC), a NF-κB pathway inhibitor, was applied to verify the mechanism by which miR-16 involved in to regulate the P-gp expression, and thus contributing to the methotrexate resistance in FLS-MTX cells. MiR-16 was upregulated in the in serum and synovial fluid from UR-MTX patients as well as in FLS-MTX cells. Inhibition of miR-16 re-sensitized the FLS-MTX cells to methotrexate by suppressing the cell viability, cell promoting cycle arrest at G0/G1 phase and enhancing apoptosis. Knockdown of miR-16 significantly reduced MDR1 mRNA expression and P-gp protein expression in FLS-MTX cells. Furthermore, inhibition of NF-κB pathway by PDTC reinforced the effect of miR-16 knockdown on P-gp expression, cell viability, cell cycle arrest and apoptosis. In conclusion, our study illustrated that inhibition of miR-16 in FLS-MTX cells alleviated methotrexate resistance by inhibiting MDR1/P-gp expression through inactivation of the NF-κB pathway.

Application of omics in predicting anti-TNF efficacy in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by progressive joint erosion. Tumor necrosis factor (TNF) antagonists are the most widely used biological disease-modifying anti-rheumatic drug in RA. However, there continue to be one third of RA patients who have poor or no response to TNF antagonists. Following consideration of the uncertainty of therapeutic effects and the high price of TNF antagonists, it is worthy to predict the treatment responses before anti-TNF therapy. According to the comparisons between the responders and non-responders to TNF antagonists by omic technologies, such as genomics, transcriptomics, proteomics, and metabolomics, rheumatologists are eager to find significant biomarkers to predict the effect of TNF antagonists in order to optimize the personalized treatment in RA.