[Effectiveness of tofacitinib combined with iguratimod in the treatment of difficult-to-treat moderate-to-severe rheumatoid arthritis].

OBJECTIVE: To investigate the efficacy and safety of iguratimod combined with tofacitinib in patients with difficult-to-treat moderate-to-severe rheumatoid arthritis (RA). METHODS: In this prospective clinical study, 30 patients with difficult-to-treat moderate-to-severe RA who attended the Department of Rheumatology and Immunology of Shanxi Province Fenyang Hospital from September 2021 to June 2022 were selected. Twenty-three patients enrollment had been treated with 2 or more conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) for more than 6 months. At least, methotrexate or leflunomide was included. Seven patients were treated with conventional synthetic DMARDs combined with tumor necrosis factor antagonists. Because all the patients had not reached the target of treatment, the combination treatment regimen of DMARDs was changed to iguratimod and tofacitinib. The observation period was 12 weeks. Clinical data were collected before and after treatment. At the end of 4 weeks, 8 weeks and 12 weeks, the clinical data were collected such as swollen joints count (SJC), tender joints count (TJC), time of morning stiffness, clinical disease activity index (CDAI), health status assessment questionnaire (HAQ), and 28-joint disease activity score (DAS28) were included. We collected laboratory indicators, recorded the patient's medication, and observed some changes to see if any adverse drug reactions occurred during the treatment. RESULTS: There were significant differences in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), platelet (PLT), SJC, TJC, DAS28 based on ESR(DAS28-ESR), time of morning stiffness, HAQ, CDAI, and anti-cyclic citrullinated peptide antibody before and after treatment. The differences had statistical significance (P < 0.05). There was no statistical differences in globulin before and after treatment (P>0.05). During the treatment of iguratimod combined with tofacitinib, there was no serious adverse reactions such as leukopenia, significant elevation of liver enzymes, allergy or thromboemblolic events that occurred in all the patients. CONCLUSION: Iguratimod combined with tofacitinib in the treatment of difficult-to-treat moderate-to-severe RA may have efficacy. The machanism was improving the patients' recent clinical symptoms by reducing inflammatory indexes. This combination treatment regimen with iguratimod and tofacitinib has a good safety profile.

Poor cardiovascular health status among Chinese women.

BACKGROUND: Systematic investigation and analysis of cardiovascular health status (CVHS) of Chinese women is rare. This study aimed to assess CVHS and atherosclerotic cardiovascular disease (ASCVD) burden in the Chinese women physicians (CWP) and community-based non-physician cohort (NPC). METHODS: In this prospective, multicenter, observational study, CVHS using the American Heart Association (AHA) defined 7 metrics (such as smoking and fasting glucose) and ASCVD risk factors including hypertension, hyperlipidemia and type-2 diabetes were evaluated in CWP compared with NPC. RESULTS: Of 5832 CWP with a mean age of 44 ± 7 years, only 1.2% achieved the ideal CVHS and 90.1% showed at least 1 of the 7 AHA CVHS metrics at a poor level. Total CVHS score was significantly decreased and ASCVD risk burden was increased in postmenopausal subjects in CWP although ideal CVHS was not significantly influenced by menopause. Compared to 2596 NPC, fewer CWP had ≥ 2 risk factors (8% vs. 27%, P < 0.001); CWP scored significantly higher on healthy factors, a composite of total cholesterol, blood pressure, fasting glucose (P < 0.001), but, poorly on healthy behaviors (P < 0.001), specifically in the physical activity component; CWP also showed significantly higher levels of awareness and rates of treatment for hypertension and hyperlipidemia, but, not for type-2 diabetes. CONCLUSION: Chinese women's cardiovascular health is far from ideal and risk intervention is sub-optimal. Women physicians had lower ASCVD burden, scored higher in healthy factors, but, took part in less physical activity than the non-physician cohort. These results call for population-specific early and improved risk intervention.

The relationship between serum fibroblast growth factor 23, Klotho, and lumbar spine bone mineral density in northern Chinese postmenopausal women.

OBJECTIVES: Changes in serum protein levels of fibroblast growth factor 23 (FGF23) and Klotho resulting from bone metabolism are still controversial. The purpose of this study was to observe the relationship between FGF23 and Klotho serum proteins and lumbar spine bone mineral density (LBMD) in northern Chinese postmenopausal women. METHODS: This was a community-based cross-sectional study carried out in Shenyang, a northern Chinese city. The study included 355 postmenopausal women with an average age of 62.92 ±â€Š8.78 years. FGF23 and Klotho serum proteins were measured using a sandwich enzyme immunoassay. LBMD was examined using dual-energy X-ray absorptiometry. Pearson's correlation and regression analyses were performed to investigate the associations among them. RESULTS: The LgKlotho was positively correlated with LBMD (r = 0.105). There was a linear relationship between LgKlotho serum levels and LBMD (P = 0.007) after adjusting for BMI, and the relationship still existed after adjustments for many confounding variables (P = 0.045), including age, BMI, systolic blood pressure, diastolic blood pressure, total protein, total bilirubin, high-density lipoprotein cholesterol, fasting blood glucose, serum calcium, estimated glomerular filtration rate, serum uric acid, estradiol, cigarette smoking, alcohol consumption, milk intake, calcium and vitamin D supplements, physical exercise, and fracture history in postmenopausal women. FGF23 serum levels were, however, not significantly associated with LBMD. CONCLUSIONS: Klotho was positively correlated with LBMD, and there was a linear relationship between Klotho serum protein levels and LBMD; however, the levels of serum Klotho were not independently associated with reduced LBMD in northern Chinese postmenopausal women. Moreover, serum FGF23 levels were not significantly related to LBMD in this sample population.

Central Blood Pressure Parameters Correlate with Cardiac Structure and Function in Healthy Chinese Individuals without Cardiovascular Disease.

PURPOSE: To explore the relationship between central blood pressure (BP) parameters and cardiac structure and function parameters in healthy individuals. METHODS: Four hundred Chinese participants with no overt cardiovascular disease participated in this study. One hundred and seventy-one participants (42.8%) were male and the mean age was 60 years. Central BP was measured with the SphygmoCor system. Cardiac structure and function were assessed by echocardiography. RESULTS: We showed a significant association of left atrial volume and left ventricular mass index (LVMI) with brachial and central systolic BP (SBP) and pulse pressure (PP; r = 0.189-0.0.39, p < 0.001). Left ventricular diastolic function and the E/A ratio were significantly associated with brachial and central BP (r = 0.228-0.469, p < 0.001). Multivariate regression analysis revealed that central SBP and PP were independently correlated with LVMI after normalization for age and other confounding variables (sex, body mass index, smoking, and alcohol intake, and the levels of triglycerides, high-density lipoprotein, low-density lipoprotein, creatinine, uric acid, fasting blood glucose, log C-reactive protein, and fibrinogen. However, only central SBP was found to be independently correlated with the E/A ratio. CONCLUSIONS: Cardiac structure and diastolic function were associated with brachial and central BP. However, after normalization, cardiac structure parameters were independently correlated with central SBP and PP. Diastolic function was the only cardiac function parameter that correlated with central SBP.

Association between the age-related decline in renal function and lumbar spine bone mineral density in healthy Chinese postmenopausal women.

OBJECTIVES: The relationship between the decline of renal function and bone mineral density (BMD) in healthy populations is not well-researched. The aim of this study was to investigate the association between the age-related decline in renal function and lumbar spine BMD (LBMD) in a community-based cross-sectional study of 390 healthy postmenopausal women (mean age 62.97 ±â€Š8.79 years) from Shenyang, China. METHODS: Dual-energy x-ray absorptiometry was used to measure LBMD. Estimated glomerular filtration rate (eGFR) was calculated using a modified Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for Asians and the CKD-EPI serum creatinine-cystatin c equation. Pearson's correlation analysis and binary logistic regression were used to evaluate associations. RESULTS: The eGFR-ASIA and eGFR-Scys were positively correlated with LBMD (r = 0.120 and r = 0.108, respectively). After adjustments for numerous potential confounders, the odds ratio for participants with LBMD decline in eGFR-ASIA quartile 3 group and 4 group were 2.45 (95% confidence interval [CI] 1.12-5.38, P < 0.05) and 3.89 (95% CI 1.55-9.76, P < 0.01), respectively, with P = 0.003 for the trend in eGFR-ASIA compared with the lowest quartile 1 group of eGFR-ASIA, where the odds ratio of eGFR-Scys for the quartile of 3 and 4 groups were 2.47 (95% CI 1.09-5.62, P < 0.05) and 2.63 (95% CI 1.10-6.29, P < 0.05), respectively, with P = 0.016 for the trend in eGFR-Scys compared with the lowest quartile 1 group of eGFR-Scys. CONCLUSIONS: The renal function decline was independently associated with decreased LBMD, and it was possible that the age-related decline in kidney function was an independent risk factor for decreased LBMD in healthy Chinese postmenopausal women.

A correlation study of telomere length in peripheral blood leukocytes and kidney function with age.

The current study aimed to investigate the association between telomere length in peripheral blood leukocytes and kidney function in various age groups of a healthy population. A total of 139 healthy individuals were divided into five groups according to their age: 35­44, 45­54, 55­64, 65­74 and >75 years old. Peripheral blood leukocytes were obtained and the telomere restriction fragment (TRF) length was assayed using a digoxigenin­labeled hybridization probe in Southern blot assays. Laboratory assays of kidney function were also performed. A correlation was observed between TRF length and age (r=­0.314, P<0.001), with the telomere length of the individuals >75 years group being significantly shorter than the telomere length of the 35­44, 45­54 and 55­64 years age groups (P<0.05). By contrast, the TRF length for males versus females did not differ for any of the age groups, while a correlation was observed between TRF length and serum levels of cystatin C (r=­0.195, P<0.05). There was also a correlation between TRF length and glomerular filtration rate (r=­0.184, P<0.05). The current study demonstrated that in this cohort, leukocyte telomere length reduced with age and was correlated with serum levels of cystatin C and glomerular filtration rate. Therefore, TRF length is associated with kidney function and may serve as a marker of aging.

Select aging biomarkers based on telomere length and chronological age to build a biological age equation.

The purpose of this study is to build a biological age (BA) equation combining telomere length with chronological age (CA) and associated aging biomarkers. In total, 139 healthy volunteers were recruited from a Chinese Han cohort in Beijing. A genetic index, renal function indices, cardiovascular function indices, brain function indices, and oxidative stress and inflammation indices (C-reactive protein [CRP]) were measured and analyzed. A BA equation was proposed based on selected parameters, with terminal telomere restriction fragment (TRF) and CA as the two principal components. The selected aging markers included mitral annulus peak E anterior wall (MVEA), intima-media thickness (IMT), cystatin C (CYSC), D-dimer (DD), and digital symbol test (DST). The BA equation was: BA = −2.281TRF + 26.321CYSC + 0.025DD − 104.419MVEA + 34.863IMT − 0.265DST + 0.305CA + 26.346. To conclude, telomere length and CA as double benchmarks may be a new method to build a BA.

Associations between bone mineral density and subclinical atherosclerosis: a cross-sectional study of a Chinese population.

CONTEXT: The significance of associations between bone mineral density (BMD) and atherosclerosis in the Asian population is less clear. OBJECTIVE: The aim of this study was to explore the population-level associations between BMD and subclinical atherosclerosis. DESIGN AND SETTING: This was a community-based cross-sectional study conducted in Shenyang, China. PARTICIPANTS: A total of 385 Chinese women and men aged 37-87 years were studied. MAIN OUTCOME MEASURES: The BMD was measured at the total hip and lumbar spine using dual-energy x-ray absorptiometry. The ankle-brachial index (ABI), pulse wave velocity (PWV), and carotid intima-media thickness (CIMT) were measured to assess atherosclerosis. Multiple regression analysis was applied to study the associations. Multicolinearity was examined using the variance inflation factor, condition index, and variance proportions. Factor analysis and principal component regression were used to remove the problem of multicolinearity. RESULTS: The differences of ABI, PWV, and CIMT among the normal BMD, osteopenia, and osteoporosis groups were not found. Total hip BMD was correlated with ABI in women after adjustment for age (r = 0.156). Sex-specific regression models included adjustment for age, body mass index, cigarette smoking, alcohol consumption, menopausal status (women), systolic blood pressure, diastolic blood pressure, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, serum uric acid, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and fibrinogen. Total hip BMD was associated with ABI in women after adjustment for age (per SD decrease in ABI: -0.130 g/cm(2), P = .022), but the association was borderline significant after full adjustment (P = .045). Total hip BMD and lumbar spine BMD were not associated with ABI, PWV, and CIMT after full adjustment in participants without a fracture history. The risk of osteoporosis was not associated with ABI, PWV, and CIMT. CONCLUSIONS: Low BMD is not associated with subclinical atherosclerosis as assessed by ABI, PWV, and CIMT.

[Estimation of individual biological aging and individualized evaluation of biomarkers of aging in healthy people].

OBJECTIVE: To estimate the degree of biological aging for healthy people by the biological age score equation and observe the differences of various aging biomarkers so as to provide targets for clinical anti-aging intervention. METHODS: A total of 2876 subjects aged 30 - 98 years old were recruited from 3 Chinese cities in 2003. After screening, 852 healthy subjects were finally selected and assigned into 4 groups according to ages: young group (< 45 yr), middle-aged group (45 - 59 yr), young-elder group (60 - 74 yr) and elder group (≥ 75 yr). They received a total of 108 physical, morphological, physiologic and biochemical examinations. The biological age score equation was employed to compute the individual biological age scores for all subjects. Then the biological age score was taken as a dependent variable and the chronological age as an independent variable for linear regression. Based on the confidence interval with ± 1 standard deviation of regression line, they were divided into 3 groups (delayed aging, normal aging and early aging). According to the chronological ages and degrees of aging, two-way analysis of variance was conducted for the following 7 biomarkers: end diastolic velocity (EDV), intima-media thickness (IMT), ratio of peak velocity of early filling to atrial filling (E/A), mitral valve annulus lateral wall of peak velocity of early filling (MVEL), arterial pulse pressure (PP), fibrinogen (FIB) and cystatin C (CYSC). At the same time, the differences of 7 biomarkers were observed in different aging groups in 4 age groups. RESULTS: (1) A comparison of biological age score: there were no significant differences in chronological age among 3 biological aging groups in same chronological age groups. However, there were some significant differences in biological age score (young group: F = 91.8, P < 0.01; middle-aged group: F = 134.5, P < 0.01; young-elder group: F = 199.5, P < 0.01; elder group: F = 82.1, P < 0.01). (2) Two-way analysis of variance (aging groups and chronological age groups for biomarkers): there were significant differences of 7 biomarkers in different chronological age groups and different aging groups. (3) A comparison of biomarkers among aging groups: there were significant differences in PP among 3 aging groups in 4 age groups. PP increased significantly in early aging group to normal aging group and delayed aging group (young group: 49.0 ± 6.9, 37.6 ± 6.4, 30.8 ± 7.6 mm Hg, F = 93.2, P < 0.01; middle-aged group: 52.9 ± 7.3, 44.3 ± 5.9, 32.7 ± 8.4 mm Hg, F = 125.7, P < 0.01; young-elder group: 61.9 ± 7.6, 51.6 ± 6.6, 37.1 ± 8.7 mm Hg, F = 196.5, P < 0.01; elder group: 72.2 ± 13.7, 61.1 ± 6.8, 43.8 ± 10.8 mm Hg, F = 60.2, P < 0.01). There were significant differences in EDV among 3 aging groups in 4 age groups. EDV increased significantly in early aging group to normal aging group and delayed aging group. There were significant changes in IMT, MVEL, E/A, CYSC and FIB among aging groups in different age groups. CONCLUSION: (1) Biological age score plays an essential role in the evaluation of aging. Based on individual evaluation of biological age score, the degrees of aging can be categorized by grouping so that a clinician may provide clinical anti-aging interventions within the target groups. (2) The above 7 biomarkers are competent for the evaluation of aging. They can not only be used to construct biological age score equation, but also provide clinical targeted interventions for aging.

Association between kidney and cardiac diastolic function in Chinese subjects without overt disease: correlation with ageing and inflammatory markers.

BACKGROUND: Age-related changes in kidney structure and function have been well documented. This study aimed to assess the relationship between declines of normal ageing-related kidney function and cardiac diastolic function in a healthy Chinese population. MATERIALS AND METHODS: A total of 852 healthy adults aged 30-98 years were enrolled and divided into four groups according to quartiles of estimated glomerular filtration rate (eGFR) and cystatin C (CYSC). Cardiac diastolic function was measured by ratio of peak velocity of early filling to peak velocity of atrial filling (E/A), which was derived by B-mode echocardiography. Lower E/A was defined as measures under the 25th percentile of sample distribution (0·784). RESULTS: Age was significantly associated with eGFR (r = -0·102, P < 0·01), CYSC (r = 0·544, P < 0·01) and E/A (r = -0·381, P < 0·01). Binary logistic regression analysis revealed that second, third and fourth quartile groups of CYSC and fourth quartile of eGFR were significantly associated with lower E/A in an unadjusted model. However, these associations were lost after full adjustment. CONCLUSIONS: Our results confirm that ageing is a major factor contributing to declines in both kidney and cardiac diastolic function in a healthy population. Adjustment for covariates, however, showed that normal ageing-related declines in kidney function and cardiac diastolic function are not independently linked.

[Correlation of cardiovascular risk factors versus glomerular filtration rate in healthy population].

OBJECTIVE: To evaluate the relationship between cardiovascular risk factors and glomerular filtration rate in healthy population. METHODS: A community-based cross-sectional study was conducted in Shenyang. The Framingham sex-specific risk equation was employed to evaluate the cardiovascular risk factors of 501 healthy study objects, calculate Framingham risk score and estimate the risk of 10-year coronary heart disease (CHD). A total of 501 study subjects were then divided into 3 groups according to 10-year CHD risk: low risk group (< 10%), moderate risk group (10% -20%) and high risk group ( > 20%). Study subjects were also divided into 5 groups according to age: < or = 44 years old; 45 - 54 years old; 55 - 64 years old; 65 - 74 years old and > or = 75 years old. The Cockcroft-Gault equation (GFR(CG)), abbreviated MDRD equation (GFR(MDRD1)) and modified MDRD equation (GFR(MDRD2)) were used to estimate glomerular filtration rate (GFR). Glomerular filtration rate (GFR) were compared among different risk groups and correlation coefficients between Framingham risk score and glomerular filtration rate calculated. RESULTS: GFR(CC), GFR(MDRD1) and GFR(MDRD2) in the low risk group was [(103 +/- 27) ml x min(-1) GFR(MDRD2) in moderate risk group all decreased [(84 +/- 24) ml x min(-1) x (1.73 m2) (-1), (101 +/- 27) ml x min(-1) x (1.73 m2) (-1), (124 +/- 33)ml x min(-1) (1.73 m2) (-1), all P < 0.01]. GFR(CG), GFR(MDRD1) and GFR(MR(MDRD2) in the high risk group all decreased [(71 +/- 15) ml x min(-1) (1.73 m2) (-1), (88 +/- 15) ml x min(-1) x (1.73 m2)(-1), (109 +/-18)ml x min(-1) x (1.73 m2) (-1), all P < 0.01]. The GFR(CG), GFR(MDRD1) and GFR(MDRD2) in the high risk group all decreased compared with the moderate risk group (P < 0.05). There was a significantly inverse correlation between Framingham risk score and GFR with the Pearson correlation coefficient -0.586 (GFR(CG), P < 0.01) and -0.449 (GFR(MDRD1) and GFR(MDRD2), P < 0.01). CONCLUSION: There is an inverse correlation between cardiovascular risk factors and GFR in healthy population. With the increasing of risk factors and their severity, Framingham risk score increases and GFR decreases.