Application of methylation in the diagnosis of ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease, mainly characterized by perifibrocartilage osteitis of the sacroiliac joints and spinal enthesitis. To date, the exact pathogenesis of AS remains elusive. It is generally believed that AS is a multifactorial disease involving genetics, infection, environment, and immunity. Among them, genetic factors are the primary determinants of disease risk and severity. In recent years, epigenetic mechanisms such as DNA methylation have been extensively surveyed with respect to the pathogenesis of AS. This review summarizes the latest research progress of methylation in AS, from whole-genome sequencing to individual differentially methylated gene. And finally, the role of methylase in AS inflammation, autophagy, and osteogenic differentiation was explored. In summary, the results of this review attempt to explain the role of methylation in the occurrence and development of AS and point out the shortcomings of current methylation research, providing directions for subsequent methylation research in AS.

Validation of Jianpi Qingre Tongluo Recipe in Reducing Inflammation and Dyslipidemia in Osteoarthritis via Lnc RNA HOTAIR/APN/PI3K/AKT.

Objective: Jianpi Qingre Tongluo Recipe (JQP) has been widely used in clinical practice, and its anti-Osteoarthritis (OA) effectiveness and specific mechanism have been concerned. This study aims to explore the clinical effect of JQP in reducing inflammation and dyslipidemia in OA and the molecular mechanism. Methods: The clinical efficacy of JQP in OA treatment was assessed through data mining. Through the network pharmacology technology, the interactive network of "active component-target-disease" was developed, the interaction relationship of the related proteins was analyzed, and enrichment analysis of gene pathway biological process was conducted. Molecular docking was carried out with PyMOL and AutodockTools-1.5.7. Finally, cell experiments were used to verify JQP's delay of immune inflammation in OA. Results: We found that JQP could ameliorate the immune inflammatory and lipid metabolism indicators; reduce VAS and SAS score in OA. A total of 98 genes overlapped between target genes of JQP and OA. TNF, IL-6, IL-1ß, and AKT1 shared the highest centrality among all target genes. KEGG analysis unveiled that 98 intersection genes were predominantly enriched in PI3K/AKT pathway in the anti-OA system. In vitro, after peripheral blood mononuclear cell (PBMC) stimulation, inflammatory cytokines imbalances and the expressions of adiponectin (APN) were decreased in osteoarthritis-chondrocytes (OA-CH). Furthermore, JQP-containing serum protected OA-CHs through down-regulating HOTAIR levels, thereby up-regulating APN and depressing PI3K/AKT pathway. Conclusion: This study suggests that JQP might reduce inflammation and improve lipid metabolism of OA by regulating HOTAIR/APN/PI3K/AKT. Our results bring a new solution for OA.

Jianpi Qingre Tongluo Decoction exerted an anti-inflammatory effect on AS by inhibiting the NONHSAT227927.1/JAK2/STAT3 axis.

Purpose: This study aims to determine whether Jianpi Qingre Tongluo Decoction (JQP) alleviates ankylosing spondylitis (AS) inflammation via the NONHSAT227927.1/JAK2/STAT3 axis. Methods: The effect of JQP on immune-inflammatory indicators in AS patients was explored through a combination of data mining, association rule analysis, and random walk model evaluation. Subsequently, network pharmacology and molecular docking were performed to screen out the potential signaling pathway. ELISA, PCR and wb were used to evaluate the effect of JQP on AS-FLS activity and inflammatory factors. The role of NONHSAT227927.1/JAK2/STAT3 combination in inflammation was studied by editing NONHSAT227927.1 and adding the JAK2/STAT3 inhibitor AG490. Involvement of the JAK2/STAT3 pathway was detected by PCR, WB, or immunofluorescence analysis. Results: Retrospective data mining results show that JQP can effectively reduce the immune inflammatory response in AS patients. Through network pharmacology and molecular docking, it is speculated that JQP exerts its effect on AS through the JAK2/STAT3 pathway. Overexpression of NONHSAT227927.1 activated the JAK2/STAT3 pathway and promoted the expression of inflammatory factors, while serum containing JQP reversed the effects of NONHSAT227927.1 overexpression. NONHSAT227927.1 silencing inhibits the proliferation of AS-FLSs, inhibits the levels of inflammatory factors, and reduces the expression of JAK2/STAT3 protein. After adding the pathway blocker AG490, it was observed that the cell viability of AS-FLSs was reduced by inflammatory factors and the levels of JAK2/STAT3 were inhibited. , and overexpression of NONHSAT227927.1 can reverse this trend. Conclusions: JQP exerted an anti-inflammatory effect on AS by inhibiting the NONHSAT227927.1/JAK2/STAT3 axis.

Exploring the mechanism of luteolin improving immune and inflammatory responses in systemic sclerosis based on systems biology and cell experiments.

There is a growing trend of applying traditional Chinese medicine (TCM) to treat immune diseases. This study reveals the possible mechanism of luteolin, an active ingredient in the core prescription of TCM, in alleviating systemic sclerosis (SSc) inflammation. Bibliometrics was performed to retrieve the core keywords of SSc inflammation. The key inflammatory indicators in the serum samples of 50 SSc patients were detected by ELISA. Data mining was applied for correlation analysis, association rule analysis, and binary logistic regression analysis on the clinical indicators and medication of 50 SSc patients before and after treatment to determine the core prescription. Network pharmacology was used for identifying candidate genes and pathways; molecular docking was conducted to determine the core monomer components of the prescription, providing a basis for subsequent in vitro molecular mechanism research. The effect of luteolin on SSc-human dermal fibroblasts (HDF) viability and inflammatory factors was evaluated by means of ELISA, RT-PCR, and Western blot. The role of TNF in inflammation was explored by using a TNF overexpression vector, NF-κB inhibitor (PKM2), and SSc-HDF. The involvement of TNF/NF-κB pathway was validated by RT-PCR, Western blot, and immunofluorescence. TCM treatment partially corrected the inflammatory changes in SSc patients, indicating its anti-inflammatory effects in the body. Atractylodes, Yam, Astragalus root, Poria cocos, Pinellia ternata, Salvia miltiorrhiza, Safflower, Cassia twig, and Angelica were identified as the core prescriptions for improving inflammatory indicators. Luteolin was the main active ingredient in the prescription and showed a strong binding energy with TNF and NF-κB. Luteolin exerted anti-inflammatory effects in vitro by reducing inflammatory cytokines in SSc-HDF and inhibiting the activation of TNF/NF-κB. Mechanistically, luteolin inhibited the activation of the TNF/NF-κB pathway in SSc-HDF, as manifested by an increase in extranuclear p-P65 and TNF but a decrease in intranuclear p-P65. Interestingly, the addition of PKM2 augmented the therapeutic function of luteolin against inflammation in SSc-HDF. Our study showed the TCM alleviates the inflammatory response of SSc by inhibiting the activation of the TNF/NF-κB pathway and is an effective therapeutic agent for the treatment of SSc.

The Independent Value of Neutrophil to Lymphocyte Ratio in Gouty Arthritis: A Narrative Review.

Since the incidence of gouty arthritis (GA) exhibits yearly increases, accurate assessment and early treatment have significant values for improving disease conditions and monitoring prognosis. Neutrophil to lymphocyte ratio (NLR) is a common indicator in blood routine, which has the characteristics of easy access and low cost. In recent years, NLR has been proven to be an effective indicator for guiding the diagnosis, treatment, and prognosis of various diseases. Moreover, NLR has varying degrees of relationship with various inflammatory biomarkers, which can affect and reflect the inflammatory response in the body. This paper reviews the independent value of NLR for GA and its underlying molecular pathological mechanisms, intending to contribute to the further application of NLR.

[Correlation between traditional Chinese medicine and reduced risk of readmission in rheumatoid arthritis patients with hypoproteinemia:a retrospective cohort study].

This study aimed to explore the correlation between traditional Chinese medicine(TCM) and reduced risk of readmission in patients having rheumatoid arthritis with hypoproteinemia(RA-H). A retrospective cohort study was conducted on 2 437 rheumatoid arthritis patients in the information system database of the First Affiliated Hospital of Anhui University of Chinese Medicine from 2014 to 2021, and 476 of them were found to have hypoproteinemia. The patients were divided into TCM users and non-TCM users by propensity score matching. Exposure was defined as the use of oral Chinese patent medicine or herbal decoction for ≥1 month. Cox regression analysis was performed to explore the risk factors of clinical indicators of rheumatoid arthritis. Additionally, the use of TCM during hospitalization was analyzed, and analysis of association rules was conducted to investigate the correlation between TCM, improvement of indicators and readmission of patients. Kaplan-Meier survival curve was plotted to compare the readmission rate of TCM users and non-TCM users. It was found the readmission rate of RA-H patients was significantly higher than that of RA patients. By propensity score matching, 232 RA-H patients were divided into TCM group(116 cases) and non-TCM group(116 cases). Compared with the conditions in the non-TCM group, the readmission rate of the TCM group was lowered(P<0.01), and the readmission rate of middle-aged and elderly patients was higher than that of young patients(P<0.01). Old age was a risk factor for readmission of RA-H patients, while TCM, albumin(ALB) and total protein(TP) were the protective factors. During hospitalization, the TCMs used for RA-H patients were mainly divided into types of activating blood and resolving stasis, relaxing sinew and dredging collaterals, clearing heat and detoxifying, and invigorating spleen and resolving dampness. The improvement of rheumatoid factor(RF), immunoglobulin G(IgG), erythrocyte sedimentation rate(ESR), C-reactive protein(CRP) and ALB was closely related to TCM. On the basis of western medicine treatment, the application of TCM could reduce the readmission rate of RA-H patients, and longer use of TCM indicated lower readmission rate.

Chinese herbal compound Huangqin Qingrechubi capsule reduces lipid metabolism disorder and inflammatory response in gouty arthritis via the LncRNA H19/APN/PI3K/AKT cascade.

CONTEXT: Gouty arthritis (GA) is a characteristically inflammatory disease often associated with lipid metabolism disorder. Huangqin Qingrechubi capsule (HQC) has been used for the treatment of GA. OBJECTIVE: To explore the mechanism of HQC in the treatment of GA. MATERIALS AND METHODS: A total of 30 GA patients (GA group) and 30 healthy subjects [normal control (NC) group] were recruited. The GA group was treated with HQC (3.6 g/d) for 10 days. Lipid metabolism and inflammation indexes were detected. Five herbal names of HQC, or 'gouty arthritis', 'hyperlipidemia' and 'inflammation' were used as key words to search related databases for network pharmacological analysis. Subsequently, GA-fibroblast-like synoviocytes (FLSs) were stimulated with GA-peripheral blood mononuclear cells (PBMCs) (3:1) and treated with HQC drug-containing serum (20%). RT-qPCR, Western blot, and ELISA were conducted to further explore the mechanism of HQC in improving GA. RESULTS: In clinical observation, HQC decreased the expression of lncRNA H19 and IL-1ß, and increased the expression of adiponectin (APN) and IL-4 in the GA group (about half). Through network pharmacology, the PI3K/AKT signaling pathway was identified. Cell experiments showed that HQC treatment reduced the viability of GA-FLSs (49.61%), up-regulated the expression of IL-4 (155.18%), IL-10 (165.13%), and APN (31.24%), and down-regulated the expression of lncRNA H19 (33.70%), IL-1ß (64.70%), TNF-α (78.32%), p-PI3K (48.80%), and p-AKT (53.48%). DISCUSSION AND CONCLUSIONS: HQC improved lipid metabolism disorder and inflammatory response of GA by regulating the lncRNA H19/APN/PI3K/AKT. Maintaining the stability of lipid metabolism may be an effective way to alleviate GA.

Traditional Chinese Medicine Compound Preparations Are Associated with Low Disease-Related Complication Rates in Patients with Rheumatoid Arthritis: A Retrospective Cohort Study of 11,074 Patients.

Objective: To evaluate whether traditional Chinese medicine compound preparations (TCMCPs) are associated with rheumatoid arthritis- (RA-) related complications (including readmission, Sjogren's syndrome, surgical treatment, and all-cause death) in patients with RA. Methods: Clinical outcome data were retrospectively collected from patients with RA discharged from the Department of Rheumatology and Immunology of the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2009 to June 2021. The propensity score matching method was used to match baseline data. Multivariate analysis was conducted to analyze sex, age, the incidence of hypertension, diabetes, and hyperlipidemia and identify the risk of readmission, Sjogren's syndrome, surgical treatment, and all-cause death. Users of TCMCP and nonusers of TCMCP were defined as the TCMCP and non-TCMCP groups, respectively. Results: A total of 11,074 patients with RA were included in the study. The median follow-up time was 54.85 months. After propensity score matching, the baseline data of TCMCP users corresponded with those of non-TCMCP users, with 3517 cases in each group. Retrospective analysis revealed that TCMCP significantly reduced clinical, immune, and inflammatory indices in patients with RA, and these indices were highly correlated. Notably, the composite endpoint prognosis for treatment failure in TCMCP users was better than that in non-TCMCP users (HR = 0.75 (0.71-0.80)). The risk of RA-related complications in TCMCP users with high-exposure intensity (HR = 0.669 (0.650-0.751)) and medium-exposure intensity (HR = 0.796 (0.691-0.918)) was significantly lower than those in non-TCMCP users. An increase in exposure intensity was associated with a concomitant decrease in the risk of RA-related complications. Conclusion: The use of TCMCPs, as well as long-term exposure to TCMCPs, may lower RA-related complications, including readmission, Sjogren's syndrome, surgical treatment, and all-cause death, in patients with RA.

Correlation analysis of differentially expressed long non-coding RNA HOTAIR with PTEN/PI3K/AKT pathway and inflammation in patients with osteoarthritis and the effect of baicalin intervention.

OBJECTIVE: This study aims to investigate the correlation of long non-coding RNA HOX transcript antisense RNA (lncRNA HOTAIR) with the PTEN/PI3K/AKT pathway and clinical-related indicators in osteoarthritis (OA) and determine the effect of baicalin intervention. METHODS: The levels of clinical lipid metabolism indexes and immune-inflammatory indexes in OA patients and normal controls was detected. OA chondrocytes (OA-CHs) were induced with peripheral blood mononuclear cells (PBMCs), followed by baicalin treatment (50 ug/mL). RT-qPCR was performed to measure lncRNA HOTAIR expression. The levels of inflammatory cytokines and adiponectin were detected using ELISA kits. CCK-8 assay was used to assess the viability of CHs. The related protein expression was measured using Western blot analysis. RESULTS: LncRNA HOTAIR might act as a biomarker of OA in vivo. LncRNA HOTAIR was positively correlated with TC, hs-CRP, IgA, TNF-α, and VAS score. Overexpression of lncRNA HOTAIR in vitro inhibited cell proliferation, reduced IL-10 and PTEN expression, but augmented TNF-α, p-PI3K, and p-AKT proteins in OA-CHs stimulated by OA-PBMCs. The changes of above indexes were also observed in OA-CHs stimulated by OA-PBMCs treated with si-lncRNA HOTAIR or baicalin, implying the synergistic effects of baicalin and lncRNA HOTAIR silencing on OA. CONCLUSIONS: Conclusively, lncRNA HOTAIR was highly expressed in OA-CHs, which facilitated OA inflammatory responses by orchestrating inflammatory cytokines and the PTEN/PI3K/AKT pathway. Baicalin exerted therapeutic effects by inhibiting the expression of lncRNA HOTAIR, decreasing the protein levels of p-PI3K and p-AKT, and increasing the protein levels of PTEN, APN, and ADIPOR1.

Xinfeng capsule inhibits inflammation and oxidative stress in rheumatoid arthritis by up-regulating LINC00638 and activating Nrf2/HO-1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xinfeng capsule is a traditional Chinese medicine compound, which has been clinically used for more than 20 years in the treatment of rheumatoid arthritis (RA), ankylosing spondylitis, osteoarthritis and its extracurricular lesions. However, the molecular role of XFC in the treatment of RA remains unclear. OBJECTIVE: This study aims to explore the efficacy and potential mechanism of XFC through retrospective data mining analysis, animal experiments and cell experiments. METHODS: The effect of XFC on clinical laboratory indexes of RA patients was observed using data mining techniques combined with association rule analysis and a random walk model. Afterwards, a rat model of adjuvant arthritis (AA) was established with Freund's complete adjuvant, followed by the observation of pathological changes in synovial tissues and the ultrastructure of synoviocytes. A RA cell model was constructed by inducing fibroblast-like synoviocytes (FLSs) with tumor necrosis factor-alpha (TNF-α) to assess the effects of XFC-containing serum on inflammation and oxidative stress through long non-coding RNA LINC00638. RESULTS: In retrospective data mining, XFC effectively reduced immune inflammation and increase the level of antioxidant enzymes in RA patients. Subsequently, animal experiments showed that XFC significantly repressed immune inflammation, oxidative stress, synovial hyperplasia, and cartilage destruction, while improving the ultrastructure of synoviocytes in AA rats. XFC-containing serum diminished the proliferation of TNF-α-induced RA-FLSs, increased LINC00638 expression (P＜0.01), decreased interleukin-6 (IL-6), IL-17, reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels (P＜0.01), and increased the protein expression of nuclear factor erythrocyte 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and superoxide dismutase 2 (SOD2) (P＜0.01). Furthermore, rescue experiments manifested that XFC-containing serum reversed the effects of silencing LINC00638 on inflammation and oxidative stress in RA-FLSs. CONCLUSION: XFC inhibits inflammation and oxidative stress in RA by up-regulating LINC00638 and activating Nrf2/HO-1 pathway.

Traditional Chinese Medicine Is Associated with Reduced Risk of Readmission in Rheumatoid Arthritis Patients with Anemia: A Retrospective Cohort Study.

Objective: This study aimed to analyze the effect of traditional Chinese medicine (TCM) on the risk of readmission for rheumatoid arthritis (RA) patients with anemia. Methods: In this study, 893 hospitalized RA patients were followed up by telephone. A retrospective cohort study was conducted using propensity score matching (PSM). The Cox proportional hazards model was used to assess the influence of various factors on the risk of readmission for RA patients with anemia. The Kaplan-Meier survival curve was utilized to analyze the effect of TCM intervention time on readmission. Results: The incidence of anemia was 58.08% (471/811) in RA patients. After 1 : 1 PSM, 328 RA patients with anemia and 328 RA patients without anemia were finally included in our study. The readmission rate of anemia patients was higher than that of patients without anemia (P < 0.01). The readmission rate of RA patients with anemia was obviously lower in the TCM group than in the non-TCM group (P < 0.01). The Cox proportional hazards model showed TCM as an independent protective factor as it decreased the risk of readmission by 50% (HR = 0.50, 95% CI = 0.27-0.94, P=0.03) in RA patients with anemia. In addition, the risk of readmission was dramatically diminished in the high-exposure subgroup (TCM > 12 months) compared with the low-exposure subgroup (TCM ≤ 12 months) (log-rank P=0.016). Conclusion: TCM, as a protective factor, is associated with a reduced risk of readmission in RA patients with anemia.

Efficacy and Safety of Qinpi Tongfeng Formula in the Treatment of Acute Gouty Arthritis: A Double-Blind, Double-Dummy, Multicenter, Randomized Controlled Trial.

Objective: Traditional Chinese medicine (TCM) has certain curative effect against acute gouty arthritis (AGA), but it lacks high-quality evidence-based studies. In this randomized controlled trial, we try to evaluate the clinical efficacy and safety of Qinpi Tongfeng Formula (QPTFF) in the treatment of AGA. Methods: One hundred and fourteen patients with AGA (damp heat accumulation syndrome) who met the inclusion and exclusion criteria were randomly divided into treatment group and control group in a ratio of 1 : 1. Patients in the treatment group were treated with QPTFF, and patients in the control group were treated with diclofenac sodium sustained-release tablets for 7 days. The primary outcome measure was the change in visual analog scale (VAS) score for pain from the baseline to day 8. The secondary outcome measures were joint symptom score, TCM syndrome score, total effective rate, pain cure rate, complete pain relief time, patient satisfaction score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum uric acid level. The safety outcome measures were routine blood test, urinalysis, liver function including alanine aminotransferase and aspartate aminotransferase, renal function including blood urea nitrogen and serum creatinine, and the rate of treatment-related adverse events (TRAEs). Results: 105 patients with 53 in the treatment group and 52 in the control group completed the 7-day treatment. There was no significant difference between two groups in demographic characteristics, VAS score for pain, joint symptom score, TCM syndrome score, ESR, CRP, and serum uric acid level before enrollment at baseline (based on both the full analysis set (FAS) and per protocol set (PPS), P > 0.05). The 95% confidence interval of the difference between the eighth and first VAS score for pain of the two groups was (-0.57, 0.42) in FAS and (-0.48, 0.47) in PPS. The lower bound of both FAS and PPS is greater than the bound value of -0.7. On day 8, there was no significant difference between the two groups in joint symptom score, TCM syndrome score, total effective rate, pain cure rate, complete pain relief time, patient satisfaction score, ESR, and CRP (FAS and PPS, P > 0.05). The serum uric acid level and TRAEs in the treatment group were significantly lower than those in the control group (FAS and PPS, P < 0.05). Conclusions: QPTFF could alleviate the symptoms of patients with AGA, which is not inferior to diclofenac sodium sustained-release tablets in analgesic. Moreover, QPTFF overmatches diclofenac sodium sustained-release tablets in decreasing serum uric acid level and TRAEs. Therefore, the results provide reliable foundation for QPTTF in the treatment of AGA. Trial Registration. This study protocol was registered in Chinese Clinical Trial Registry (registration number: ChiCTR2100050638).

Overexpression of long noncoding RNA LINC00638 inhibits inflammation and oxidative stress in rheumatoid arthritis fibroblast-like synoviocytes by regulating the Nrf2/HO-1 pathway.

BACKGROUND: Abnormal expression of long noncoding RNAs (lncRNAs) is involved in several autoimmune diseases including rheumatoid arthritis (RA). In this study, we intended to explore the expression of lncRNA LINC00638 in RA and its potential mechanism of action related to inflammation and oxidative stress. METHODS: The level of LINC00638 in the peripheral blood mononuclear cells (PBMCs) obtained from 45 RA patients and 30 normal controls was analyzed and its correlation with clinical indicators was investigated. In vitro, we used tumor necrosis factor-α to stimulate fibroblast-like synoviocytes (FLS) of RA patients for cell based experiments. Subsequently, the overexpressed plasmid and small interfering RNA of LINC00638 were designed. Furthermore, we further analyzed the potential effects of LINC00638 on the proliferation and migration of RA-FLS and the nuclear factor erythrocyte derived 2 related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. RESULTS: LINC00638 expression was found to be significantly decreased in PBMCs of RA patients, and it was negatively correlated with erythrocyte sedimentation rate, interleukin (IL)-17, reactive oxygen species (ROS), and disease activity scores for 28 joints (DAS28). Overexpression of LINC00638 activated the Nrf2/HO-1 pathway, markedly decreased the expressions of IL-6, IL-17, IL-23, ROS, as well as malondialdehyde, increased the total antioxidant capacity, and attenuated the proliferation and migration of RA-FLS, while silencing of LINC00638 reversed these manifestations. CONCLUSIONS: LINC00638 was found to be expressed at low levels in RA patients and was associated with immune inflammation, oxidative stress, and disease activity. Overexpression of LINC00638 can reduce the proliferation as well as migration of RA-FLS, and activate the Nrf2/HO-1 pathway to inhibit the inflammation and oxidative stress.

Expression of LINC00638 in rheumatoid arthritis patients with damp-heat obstruction syndrome and the regulatory mechanisms for inflammation and oxidative stress. / ç±»é£Žæ¹¿å ³èŠ‚ç‚Žæ¹¿çƒ­ç—¹é˜»è¯æ‚£è€ LINC00638çš„è¡¨è¾¾åŠå ¶è°ƒæŽ§ç‚Žç—‡å’Œæ°§åŒ–åº”æ¿€çš„æœºåˆ¶.

OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and joint destruction. Both inflammatory response and oxidative stress contribute to the pathogenesis of RA. Oxidative damage can induce and aggravate the imbalance of immune inflammation and promote cell and tissue damage. In this study, the expression of long non-coding RNA (lncRNA) LINC00638 in peripheral blood of patients with RA damp-heat arthralgia syndrome was observed, and the correlation between LINC00638 and disease activity, immune inflammation and oxidative stress indicator was investigated. Subsequently, the mechanisms for LINC00638 in regulating the inflammatory response and oxidative stress in RA fibroblast-like synoviocyte (FLS) under the condition of overexpression and interference were further explored. METHODS: In this study, 48 RA patients with damp-heat arthralgia syndrome and 27 normal healthy subjects, who came from Department of Rheumatology, First Affiliated Hospital of Anhui University of Chinese Medicine, were included; and they were divided into a RA group and a control group. The expression of LINC00638 in peripheral blood mononuclear cells (PBMC) from the subjects was detected by real-time PCR. Enzyme linked immunosorbent assay (ELISA) was used to detect serum interleukin (IL)-10, IL-17, tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2) expression. Spearman method was used to study the relationship between LINC00638 and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP), and to observe the relation between LINC00638 and the Disease Activity Score of 28 Joint (DAS28), Quantitative Score of Damp Heat Syndrome, Visual Analogue Scale (VAS), Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS). RA-FLS was induced by RA-PBMC, and the RA in vitro cell experimental model was established. LINC00638 overexpression plasmid and small interfering RNA (siRNA) were constructed and transfected into RA-FLS. The cell experiments were divided into 4 groups: a pcDNA3. 1- control group, a pcDNA3.1-LINC00638 group, a siRNA-control group, and a siRNA-LINC00638 group. The transfection efficiency of overexpression plasmid and siRNA was detected by real-time PCR, the expression of TNF-α and IL-10 was detected by ELISA, and the expression of antioxidant proteins HO-1 and SOD2 was detected by immunofluorescence. RESULTS: Compared with the control group, the expression of LINC00638 in the RA group was lower (P<0.01). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of LINC00638 was 0.9271. The DAS28 in RA group was 5.70 (5.40-6.50), the Quantitative Score of Damp-heat Syndrome was 20.0 (17.0-23.0), and the VAS score was 7.0 (6.3-8.0). Compared with the control group, the ESR, CRP, RF, anti-CCP, SAS and SDS scores in the RA group were significantly increased (all P<0.01). Spearman correlation analysis showed that: LINC00638 was negatively correlated with ESR (r=-0.532, P<0.01), CRP (r=-0.367, P<0.05), TNF-α (r=-0.375, P<0.01), MDA (r= -0.295, P<0.05), DAS28 (r=-0.450, P<0.01), and which was positively correlated with SOD2 (r=0.370, P<0.05). After the induction of RA-FLS, the expression level of LINC00638 was significantly decreased (P<0.01), indicating that the stimulation of PBMC could effectively reduce the expression of LINC00638 in RA-FLS, so the experimental model of RA-FLS-induced by PBMC was utilized. Compared with the pcDNA3.1-control group, the expressions of LINC00638, IL-10, SOD2, and HO-1 in the pcDNA3.1-LINC00638 group were significantly increased (all P<0.01), and the expression of TNF-α was decreased (P<0.01). Compared with siRNA-control group, LINC00638, IL-10, SOD2 and HO-1 in the siRNA-LINC00638 group were significantly decreased (all P<0.01), and TNF-α was significantly increased (P<0.01). CONCLUSIONS: LINC00638 is down-regulated in the peripheral blood of RA patients with damp-heat arthralgia syndrome, which is correlated with disease activity, immune inflammation and oxidative stress. Overexpression of LINC00638 can down-regulate pro-inflammatory factors, up-regulate anti-inflammatory factors, and increase antioxidant enzyme activity, thereby improving inflammation and oxidative stress in RA. LINC00638 is the differential lncRNA obtained by the research group's previous high-throughput sequencing of the whole transcriptome of peripheral blood PBMCs in RA patients and validation of clinical samples. In order to deepen the molecular biology research of this gene, the microRNA and mRNA targeted by LINC00638 can be further studied from the perspective of competing endogenous RNAs.

Factors influencing the Sharp score of 1057 patients with rheumatoid arthritis and anemia: a retrospective study.

OBJECTIVE: This study examined the relationship of the Sharp score with demographic factors and clinical immune-inflammatory markers in patients with anemia in rheumatoid arthritis (RA). METHODS: The clinical data of 1057 patients with RA and anemia and 1006 patients with RA without anemia were retrospectively analyzed. Spearman's correlation coefficient analysis, association rule analysis, and logistic regression were used to study the relationships between the Sharp score and influencing factors in patients with RA and anemia. RESULTS: The incidence of anemia was 51.24% (1057/2063), and mild anemia accounted for 81.93% (866/1057) of cases. Spearman's correlation coefficient and association rule analyses revealed that the Sharp score of patients with RA and anemia was correlated with immune-inflammatory response and anemia. Logistic regression analysis illustrated that advanced age (>60 years), female, low serum iron levels, C-reactive protein positivity, and immunoglobulin A positivity were risk factors for a high Sharp score (>28.25) in patients with RA and anemia. CONCLUSION: The Sharp score is closely related to clinical disease activity and anemia, and it should be considered in the treatment strategy of patients with RA and anemia.

[Nimotuzumab in combination with chemotherapy for patients with malignant gliomas].

OBJECTIVE: Nimotuzumab is a humanized monoclonal antibody targeted against epidermal growth factor receptor (EGFR). Recent clinical studies show that patients with malignant gliomas could benefit from nimotuzumab treatment. The aim of the present study was to evaluate the efficacy and side effects of nimotuzumab in combination with chemotherapy for patients with malignant gliomas. METHODS: The patients received 200 mg of nimotuzumab infusion intravenously over 60 minutes once weekly for the first eight weeks and then once every two weeks until unacceptable toxicity or tumor progression occurred. Individualized chemotherapy was administered based on O(6)-methylguanine-DNA methyltransferase (MGMT) expression and previous chemotherapy responses in combined with nimotuzumab. RESULTS: Fourteen patients received a total of 122 times of nimotuzumab ranging from 2 to 20 (median 7.5 times). Combined chemotherapy regimens included: continuous 21-day temozolomide (10 cases), standard 5-day temozolomide (2 cases), teniposide plus cisplatin (1 case), and teniposide plus nimustine (1 case). Partial response (PR) and stable disease (SD) were found in 3 patients (21.4%)and 6 patients (42.9%), respectively. Disease control rate (PR + SD) was 64.3%. The median progression-free survival (PFS) was 4 months (95%CI: 0.7 - 7.3) and PFS at 6 months was 30.6%. The most common toxicities include grade I-II neutropenia (2 cases), thrombocytopenia (2 cases), lymphopenia (1 case), nausea and vomitting (3 case) and asymptomatic transaminase increase (1 case). One patient developed grade IV neutropenia and thrombocytopenia. One patient developed nimotuzumab-related acneiform rash. CONCLUSIONS: Nimotuzumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and the toxicities are well tolerable, therefore, worth further investigation.