Objective:To analyze the methylation characteristics of the lymphocyte-specific protein-tyrosine kinase (LCK) promoter region in the peripheral blood circulation of rheumatoid arthritis (RA) patients and its correlation with clinical indicators.Methods:Targeted methylation sequencing was used to compare the methylation levels of 7 CpG sites in the LCK promoter region in the peripheral blood of RA patients with healthy controls (HC) and osteoarthritis (OA) patients. Correlation analysis and ROC curve construction were performed with clinical information.Results:Non-parametric tests revealed that compared with HC [0.53(0.50, 0.57)] and OA patients [0.59(0.54, 0.62), H=47.17, P<0.001], RA patients [0.63(0.59, 0.68)] exhibited an overall increase in methylation levels. Simultaneously, when compared with the HC group [0.38(0.35, 0.41), 0.59(0.55, 0.63), 0.60(0.55, 0.64), 0.59(0.55, 0.63), 0.58(0.53, 0.62), 0.45(0.43, 0.49), 0.57(0.54, 0.61)], the RA group [0.46(0.42, 0.49), 0.70(0.65, 0.75), 0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] showed a significant elevation in methylation levels at CpG sites cg05350315_60, cg05350315_80, cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-5.63, -5.89, -5.91, -5.89, -5.98, -5.95, -5.95, all P<0.001). Compared with the OA group [0.65(0.59, 0.69), 0.65(0.60, 0.69), 0.64(0.58, 0.68), 0.50(0.45, 0.54), 0.63(0.58, 0.67)], the RA group [0.70(0.66, 0.76), 0.70(0.65, 0.75), 0.69(0.64, 0.74), 0.55(0.51, 0.59), 0.68(0.63, 0.73)] exhibited a significant increase in methylation levels at CpG sites cg05350315_95, cg05350315_101, cg05350315_104, cg05350315_128, and cg05350315_142, with statistically significant differences ( Z=-3.56, -3.52, -3.60, -3.67, -3.62; P=0.036, 0.042, 0.031, 0.030, 0.030). Furthermore, Pearson correlation coefficient analysis revealed a positive correlation between the overall methylation level in this region and C-reactive protein (CRP) ( r=0.19, P=0.004) and erythrocyte sedimentation rate ( r=0.14, P=0.035). The overall methylation level of the LCK promoter region in the CRP (low) group [0.63 (0.58, 0.68)] was higher than that in the CRP (high) group [0.65(0.61, 0.70)], with statistically significant differences ( Z=2.60, P=0.009). Finally, by constru-cting a ROC curve, the discriminatory efficacy of peripheral blood LCK promoter region methylation levels for identifying RA patients, especially seronegative RA patients, from HC and OA groups was validated, with an AUC value of 0.78 (95% CI: 0.63, 0.93). Conclusion:This study provides insights into the methylation status and methylation haplotype patterns of the LCK promoter region in the peripheral blood of RA patients. The overall methylation level in this region is positively correlated with the level of inflammation and can be used to differentiate seronegative RA patients from the HC and OA patients.

Cholesterol is an important precursor of many endogenous molecules. Disruption of cholesterol homeostasis can cause many pathological changes, leading to liver and cardiovascular diseases. CYP1A is widely involved in cholesterol metabolic network, but its exact function has not been fully elucidated. Here, we aim to explore how CYP1A regulates cholesterol homeostasis. Our data showed that CYP1A1/2 knockout (KO) rats presented cholesterol deposition in blood and liver. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats. Further studies found that the lipogenesis pathway (LXRα-SREBP1-SCD1) of KO rats was activated, and the key protein of cholesterol ester hydrolysis (CES1) was inhibited. Importantly, lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A. Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

Objective:To investigate the status and influencing factors of quality of life among disabled elderly whose home care services were paid by the long-term care insurance in Guangzhou, in order to provide a scientific evidence for improving their quality of life and improving the long term care insurance system.Methods:A convenience sample of 161 disabled elderly whose home care services were paid by the long-term care insurance were recruited and investigated. A cross-sectional survey was conducted by general information questionnaire, World Health Organization Quality of Life Brief Scale, Barthel Index, Self-rating Depression Scale, Self-rating Anxiety Scale and World Health Organization Happiness Index Scale.Results:The score of the quality of life among disabled elderly was 41.17±7.79. And the score of its four dimensions in descending order: environment, social relationships, psychological and physical with (11.38 ± 2.71), (10.36 ± 3.16), (9.86 ± 2.08), (9.56 ± 1.89) points. The multiple linear regression analysis found that frequencies of outdoor activities per week, frequencies of hospitalization in the past year, subjective well-being, depression and anxiety influenced the quality of life of the disabled elderly( P<0.05). Conclusions:The quality of life of disabled elderly is not optimistic. Nurses in home care institutions should formulate personalized nursing intervention based on influencing factors to improve the quality of life of disabled elderly, while providing a basis for optimizing long-term care insurance policies.

Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.

Objective:To study the genotype distribution of drug-related gene polymorphism of methotrexate (MTX) and leflunomide (LEF) in patients with rheumatoid arthritis (RA).Methods:The genotyping results of RA patients' MTX and LEF related genes(MTHFR677C/T, MTHFR1298A/C, ABCB13435T/C, DHODH19C/A and CYP1A2734C/A) detected in Shanghai Guanghua Hospital from December 2018 to May2019 and drug-related adverse effect were statisticallyanalyzed. The independence of allele distribution was tested by Hardy-Weinberg test. Counting data of genotypes and allele frequencies among the groups were analyzed by the chi-square test. Measurement data were showed as Mean±SD deviation. The network between incidence of adverse events and genotypes of patients was analyzed by cytoscape software. Results:Genotype distribution in 151 patients was consistent with Hardy-Weinberg genetic balance ( P>0.05), and genotype and allele distribution of each gene showed no statistical difference in gender ( P>0.05). The results showed that the most common genotype in RA were that genotypes of the good response with moderate resistance to MTX (MTHFR677CC/MTHFR1298AA/ABCB13435CT) (16 cases, 13.5%) and the good response with moderate side effect risk to LEF(DHODH19CC/CYP1A2734AC) (25 cases, 28.4%). According to the distribution frequency of alleles, the incidence of high side effects caused by MTX combined with LEF was predicted to be 2.9%, which was close to 1.8% of the actual genotypes of patients. The types and proportion of clinical adverse reactions in patients were retrospectively analyzed and the correlation network analysis was conducted with the genotype analysis results. It was found that the incidence rates of adverse reactions were liver injury (35.4%, 35/99), leukopenia (14.1%, 14/99), thrombocytopenia (2.0%, 2/99), and skin rash (1.0%, 1/99) from the top to the bottom. The top two genotypes that were related to the occurence of adverse events were MTHFR677CT/MTHFR1298AA/ABCB13435CT and DHODH19CA/CYP1A2734AC, respectively, which verified the consistency between drug-related genotype and clinical manifestations in RA patients. Conclusion:Our results suggested that genotype in RA patients is closely related to drug efficacy and adverse events. 2.9% of RA patients need to stop taking MTX and LEF due to high MTX resistance and poor MTX response and increased toxicity when combined with LEF, in which the proportion of liver injury is the highest.

Hyperuricemia/gout is a common metabolic disease in China, which is a serious threat to people′s health. In clinical practice, the standardization of prevention and diagnosis and the rate of treat-to-target need to be improved. There is still a lack of education for the patients about the understanding of clinical guidelines, the disease knowledge and the importance of cooperating with doctors to carry out diagnosis and treatment. From the most concerned issues of the patients, we established the hyperuricemia/gout patient practice guideline working group with multidisciplinary physicians and patients. Seventeen opinions, as the hyperuricemia/gout patient practice guidelines, are proposed in accordance with the relevant principles of the "WHO guidelines development manual" , and with the international normative process, aiming to improve the patients compliance, improve the level of health management of the disease.

In recent years, the clinical guidelines for the diagnosis and treatment of rheumatoid arthritis (RA) have been constantly updated. Among the general principles, it is particularly emphasized that, in order to improve the ratio of treat to target(T2T) of RA, doctors and patients should work together to negotiate the details of the guidelines. Therefore, it is important for patients to further understand the disease and clinical guidelines of RA, and to better cooperate with doctors. This study was based on the most concerned issues of RA patients and international standard procedure of guideline study, we organized the working group and introduce the following 16 recommendations constituting the RA patients′ practice guidelines.

Objective:To explore the real experience of family caregiver in providing care service and receiving home care organizational management after the disabled aged enjoyed the long-term care insurance so as to provide a scientific basis for standardizing the long-term care insurance home care service.Methods:From July to September 2019, this study selected 14 family caregivers of the home disabled aged enjoying the long-term care insurance in Guangzhou by purposive sampling to carry out the semi-structured interview so as to understand the personal feelings and suggestions of interviewees on long-term care insurance home care service. Colaizzi phenomenological analysis was used to data analysis.Results:A total of two themes were abstracted including the harvest of family caregiver and insufficient management model.Conclusions:Long-term care insurance home care service is instrumental in reducing the economic burden, care burden of family caregivers, and promoting the normative development of home care service. However, there is insufficient management model of family caregivers which needs to be improved.

Objective To observe the clinical efficacy of electroacupuncture plus oral administration ofZeling Guanjie Xiaozhong Heji in treating rheumatoid arthritis (RA) due to liver-kidney yin deficiency.Method Totally 126 patients with active RA due to liver-kidney yin deficiency were randomized into a treatment group and a control group, 63 cases in each group. The control group was prescribed with orally taking Methotrexate tablets and Leflunomide tablets, while the treatment group was intervened by electroacupuncture plus oral administration ofZeling Guanjie Xiaozhong Heji in addition to the medications given to the control group. The Disease Activity Score 28 (DAS28) was evaluated before and after intervention, and the therapeutic efficacies were compared based on the criteria of the American College of Rheumatoid (ACR) and syndrome of traditional Chinese medicine (TCM).Result The ACR total effective rate was 87.3% in the treatment group versus 65.1% in the control group, and the difference was statistically significant (P<0.01). The total effective rate based on TCM syndrome was 87.3% in the treatment group versus 73.0% in the control group, and the difference was statistically significant (P<0.05). There was a significant difference in comparing the DAS28 score between the two groups after intervention (P<0.01).Conclusion Electroacupuncture plus oral administration of Chinese medication and western medication is an effective approach in treating RA due to liver-kidney yin deficiency, and it can significantly enhance the therapeutic efficacy based on ACR20 and TCM syndrome.