Objective: To investigate the characteristics of non-alcoholic fatty liver disease (NAFLD) and its associated factors in rheumatoid arthritis (RA) patients. Methods: This cross-sectional study recruited 385 RA patients [including 72 (18.7%) male and 313 (81.3%) female] who received abdominal sonographic examination from August 2015 to May 2021 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. There were 28 RA patients at 16-29 years old and 32, 80, 121, 99, 25 at 30-39, 40-49, 50-59, 60-69, ≥ 70 years old, respectively. Demographic and clinical data were collected including age, gender, history of alcohol consumption, disease duration, body mass index (BMI), waist circumference, blood pressure, RA disease activity indicators and previous medications. Logistic regression analyses were used to identify the associated factors of NAFLD in RA patients. Results: The prevalence of NAFLD was 24.2% (93/385) in RA patients, 26.3% (21/80) in 40-49 age group and 33.1% (40/121) in 50-59 age group. There were 22.1% (85/385) and 3.6% (14/385) RA patients with overweight and obese, in which the prevalence of NAFLD was 45.9% (39/85) and 78.6% (11/14) respectively, which was 2.6 folds and 4.5 folds that of RA patients with normal BMI. Although there was no significant difference of age, gender and RA disease activity indicators between RA patients with or without NAFLD, those with NAFLD had higher proportions of metabolic diseases including obese (11.8% vs. 1.0%), central obesity (47.3% vs. 16.8%), hypertension (45.2% vs. 29.8%) and type 2 diabetes mellitus (24.7% vs. 12.0%), consistent with higher levels of total cholesterol [(5.33±1.31) mmol/L vs. (4.73±1.12) mmol/L], triglyceride [(1.51±1.08) mmol/L vs. (0.98±0.54) mmol/L] and low-density lipoprotein cholesterol [(3.37±0.97) mmol/L vs. (2.97±0.78) mmol/L, all P<0.05]. Multivariate logistic regression analysis showed that BMI (OR=1.314) and triglyceride (OR=1.809) were the independent factors positively associated with NAFLD in RA patients. Conclusion: NAFLD is a common comorbidity in RA patients, especially in those with middle-aged, overweight or obese, which is associated with high BMI or high triglyceride. Screening and management of NAFLD in RA patients especially those with overweight, obese or dyslipidemia should be emphasized.
Adolescent ; Adult ; Aged ; Arthritis, Rheumatoid/epidemiology* ; Cholesterol, LDL ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/epidemiology* ; Obesity/epidemiology* ; Overweight/epidemiology* ; Triglycerides ; Young Adult

Objective:To investigate the correlation between serum β-amyloid (Aβ) 42 level and cognitive impairment in patients with cerebral small vascular disease (CSVD).Methods:Consecutive patients with CSVD admitted to the Affiliated Hospital of Jining Medical University from September 2016 to September 2019 were enrolled retrospectively. Montreal Cognitive Assessment (Chinese edition), Clinical Dementia Rating and Center for Epidemiologic Studies-Depression scale were used for neuropsychological evaluations. According to the diagnostic criteria of mild cognitive impairment, they were divided into cognitive impairment group and normal cognitive function group. Multivariate logistic regression analysis was used to identify the independent risk factors for cognitive impairment in patients with CSVD. Receiver operator characteristic (ROC) curve was used to evaluate the predictive value of serum Aβ42 level for cognitive impairment. Results:A total of 171 patients with CSVD were enrolled. The serum Aβ42 was 2.14±0.56 μg/L. Eight-one patients (47.4%) had cognitive impairment, and 90 (52.6%) had normal cognitive function. Univariate analysis showed that there were significant differences in age, smoking, hypertension, diabetes, history of previous stroke or transient ischemic attack, blood pressure, fasting blood glucose and serum Aβ42 between the cognitive impairment group and the normal cognitive function group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for age, smoking, diabetes, blood pressure and history of previous stroke or transient ischemic attack, serum Aβ42 (odd ratio [ OR] 2.974, 95% confidence interval [ CI] 1.632-6.348; P=0.009), hypertension ( OR 2.063, 95% CI 1.340-5.438; P=0.021) and fasting blood glucose ( OR, 1.598, 95% CI 1.167-4.156; P=0.030) were the independent risk factors for cognitive impairment in patients with CSVD. ROC curve analysis showed that the area under the curve of serum Aβ42 was 0.700 (95% CI 0.619-0.782; P<0.001). The optimal cut-off value was 2.39 μg/L, and the sensitivity and specificity were 56.8% and 80.0%, respectively. Conclusions:Aβ42 is independently correlated with cognitive impairment in patients with CSVD, and can be used to predict cognitive impairment in patients with CSVD.

OBJECTIVE: To examine the clinical effects of Yisui Shengxue Granules () in the treatment of β-thalassemia and explore its mechanism on DNA methylation levels. METHODS: A randomized placebo-controlled double-blinded trial was conducted. Forty patients with β-thalassemia were recruited and distributed randomly by envelope method into an experimental group and a control group, 20 patients in each group. The patients were given Yisui Shengxue Granules in the experimental group and placebo in the control group (12 g/bag three times a day) during a 3-month intervention. Before and after 1, 2, and 3 months of treatment, peripheral intravenous blood was sampled, and blood parameters such as hemoglobin (Hb), red blood cells (RBCs), reticulocytes (Ret), and fetal hemoglobin (HbF) were analyzed. Mononuclear cells from 5 patients, who showed an obvious treatment effect, were isolated by density gradient centrifugation. DNA methylation was analyzed using an Affymetrix USA GeneChip Human Promoter 1.0 Array and Input-promoter 1.0. RESULTS: Compared with pre-treatment, there was an obvious increase in Hb and RBCs counts after 1, 2, and 3 months in the experiment group (P<0.01 or P<0.05). Meanwhile, HbF increased from the 2nd to the 3rd month (P<0.05). In the control group, Hb and RBCs showed no obvioas change. After 3-month treatment, DNA methylation results from 5 patients revealed that there were 24 hypomethylated genes and 3,685 hypermethylated genes compared with pre-treatment. Genes of insulin-like growth factor 1 receptor (IGF1R) and Janus kinase 3 (JAK3) revealed the most relations with other genes (degree: 21) and genes of 1-phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma 2 (PLCG2) and mitogen-activated protein kinase 10 (MAPK10) showed a stronger intermediary role (betweenness centrality=0.04). CONCLUSIONS JAK3 and MAPK10 are two key genes in bone marrow and the lymphatic system, and JAK3 is likely to be related to hematopoietic cytokines in the process of early hematopoiesis. (Registration No. NCT01549080).

OBJECTIVETo analyze the efficacy and side-effects of combination of rabbit antithymocyte globulin (ATG) and cyclosporine A (CsA) as the first-line immunosuppressive therapy (IST) for adult severe aplastic anemia (SAA) patients.

METHODSAdult SAA or very severe aplastic anemia (VSAA) patients treated with rabbit ATG + CsA as first line therapy in our hospital from 2003 to 2008 were retrospectively analysed and the therapeutic response relevant factors were analysed.

RESULTSSeventy-nine patients were enrolled. Of all these patients, 6 died within 3 months after IST. The overall response rate was 82.2% and the median time to transfusion independent was 60 days. The therapeutic response rate in 32 SAA patients (100%) was significantly higher than that in 41 VSAA cases (68.3%) (P = 0.001). Patients with neutrophil response to G-CSF treatment had a higher IST response rate than those without response to G-CSF (100% vs 67.5%, P = 0.001). Sixty-one patients (77.2%) occurred serum sickness reaction. Three patients relapsed and two developed clonal hematological abnormalities after IST. The 3-year overall survival for all the patients was 88.9%.

CONCLUSIONSRabbit ATG in combination with CsA as first-line IST for adult SAA can lead to excellent treatment outcomes with minor adverse effects.

Adolescent ; Adult ; Anemia, Aplastic ; drug therapy ; Animals ; Antilymphocyte Serum ; therapeutic use ; Cyclosporine ; therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male ; Middle Aged ; Rabbits ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the effects of cyclosporine A (CsA) whole-blood concentration on the early response to immunosuppressive therapy (IST) in severe and very severe aplastic anemia (SAA/VSAA).

METHODSNinety SAA/VSAA patients treated with rabbit antithymocyte globulin (ATG) plus CsA as first line therapy in our hospital were retrospectively analysed. CsA levels between the response group and non-response group, and response rates of patients with variant CsA levels were compared respectively.

RESULTS(1) There was no significant difference in the beginning unmodified CsA blood concentration between IST responded and non-responded SAA/VSAA patients. The beginning unmodified C(0) 133.91 ug/L in IST 2-month responders was higher than that of 49.9 ug/L in non-responded SAA patients (P = 0.009); (2) The mean CsA C(0) and C(2) levels during the third month following IST were significantly different in responders and non-responders(197.52 µg/L vs 161.49 µg/L, P = 0.024, and 738.76 µg/L vs 615.46 µg/L, P = 0.009), and no significant difference in other periods of IST (P > 0.05); (3) The response rate (87.5%) was significantly higher in patients with CsA C(0) ≥ 200µg/L the third month following IST than those of 55.6% in patients with CsA C(0) 150 - 200 µg/L (P = 0.023) and 59.3% in patients with CsA C(0) < 150 µg/L (P = 0.046), respectively. The response rate was significantly higher of C(2) ≥ 700 µg/L group than that of C(2) < 700 µg/L group (80.5%vs 55.3%, P = 0.012).

CONCLUSIONSThe CsA concentration related to the early IST response. The third month CsA concentrations was the most important for the response and maintaining CsA levels with C(0) ≥ 200 µg/L and C(2) ≥ 700 µg/L may improve the response to IST in SAA/VSAA.

Adolescent ; Adult ; Anemia, Aplastic ; blood ; therapy ; Child ; Child, Preschool ; Cyclosporine ; blood ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate bone marrow hematopoietic cells genetic instability (BMHCGI) in patients with aplastic anemia (AA) and to explore its influence on immunosupressive therapy for AA and significance on late clonal hematologic disorders.

METHODSGenetic instability of bone marrow mononuclear cells (BMMNC) was measured by Comet assay. The relationship between bone marrow failure parameters and genetic instability results was evaluated. The reciprocity of genetic instability and treatment responses to immunosuppressive therapy (IST) was investigated.

RESULTSComet assay parameters \[tail moment (TM), olive TM (OTM), comet %\] of AA patients were significantly higher than that of control group (P < 0.05). There was no statistic correlation of comet parameters of severe AA (SAA) BM hematopoietic cells with age, gender and peripheral blood cell count (P > 0.05). For the treatment response rate at six months after IST there was no statistical difference between comet cells of < 21.64% and of >/= 21.64%, and so did between OTM < 1.58 and >/= 1.58 in SAA patients. IST had no effect on SAA BMHCGI, whereas, the Comet%, TM and OTM in SAA PR patients and Comet% in CR patients were significantly decreased than those before treatment. Comet parameters of two SAA patients were significantly increased before the development of clonal cytogenetic abnormalities.

CONCLUSIONSIncreased BMHCGI may be one of the elements in the pathogenetic mechanisms in AA. The genetic instability is irrelevant to the SAA patients overall response rate of IST at six months, but IST can alleviate the genetic instabilities in responded SAA patients.

Anemia, Aplastic ; therapy ; Blood Cell Count ; Bone Marrow Cells ; Humans ; Immunosuppression ; Pancytopenia

OBJECTIVETo analyse the efficacy and side-effects of rabbit antithymocyte globulin (ATG) and cyclosporin A (CsA) as the first-line therapy for childhood severe aplastic anemia (SAA).

METHODSSeventy-one childhood SAA patients treated with rabbit ATG + CsA as first line therapy were retrospectively analysed.

RESULTSSeventy-one SAA patients, including 38 SAA and 33 very severe aplastic anemia (VSAA), were enrolled. The median age was 12 years. Of these patients, 3 died within 3 months after the immunosuppressive therapy (IST). The overall response rate was 67.6% (46/68) and the median time to transfusion independent was 53 days. Thirty-three patients (48.5%) obtained remission in 3 months after the IST and 45 (67.2%) in 6 months. The response rates were 57.7% (15/26), 56.5% (13/23) and 94.7% (18/19) for patients less than 10 years old, 10 - 15 year-old and 15 - 18 year-old, respectively. Sixty patients suffered from serum sickness on the IST. Three patients relapsed and another 3 unrespond patients received retreatment of IST, and one patient progressed to myelodysplastic syndromes (MDS).

CONCLUSIONRabbit ATG in combination with CsA as first line therapy for childhood SAA/VSAA can lead to overall response rate of 67.6% with minor adverse effects.

Anemia, Aplastic ; therapy ; Animals ; Antilymphocyte Serum ; Cyclosporine ; therapeutic use ; Humans ; Immunosuppressive Agents ; therapeutic use ; Rabbits ; Treatment Outcome

OBJECTIVETo investigate the impact of immunosuppressive therapy (IST) on genetic instabilities of bone marrow hematopoietic cells (BMHCs) in patients with aplastic anemia (AA).

METHODSComet assay as used to detect genetic instabilities of hematopoietic cells from patients, and the percent of DNA in comet tail (TDNA), tail length (TL), tail moment (TM), olive tail moment (OTM) and the rate of comet cells were measured. BMHCs from AA patients were examined with comet assay before and after IST, and the results were compared with those from controls.

RESULTSComet parameters from 91 AA patients including TDNA, TL, TM, OTM comet cell percentage were (5.0 +/- 4.0)%, 11.3 +/- 7.2, 1.7 +/- 2.0, 1.5 +/- 1.4, (16.8 +/- 13.7)%, respectively, which were significantly higher than those from control group (P < 0.05). There were statistical differences between the comet parameters of severe AA (SAA)/non-SAA (NSAA) and those of control group (P < 0.05), but no difference in the comet parameters between SAA and NSAA patients (P > 0.05). The TDNA, TL, TM, OTM and comet cells percentage were (4.4 +/- 3.6)%, 10.4 +/- 7.5, 1.4 +/- 1.6, 1.3 +/- 1.4 and (20.2 +/- 21.2)%, respectively at 3 months after IST in 53 SAA patients and were (3.7 +/- 3.3)%, 10.0 +/- 7.2, 1.2 +/- 1.8, 1.1 +/- 1.3 and (18.5 +/- 19.0)% respectively at 6 months after IST in 30 SAA patients, being no statistical difference from those of 58 SAA patients before IST (P values were all > 0.05).

CONCLUSIONBMHCs of AA had inherent genetic instabilities which were not increased by recent IST. It indicated that there was no correlation between IST and the development of clonal hematologic disorders in AA.

Adolescent ; Adult ; Anemia, Aplastic ; genetics ; therapy ; Child ; Child, Preschool ; Comet Assay ; Female ; Genomic Instability ; Hematopoietic Stem Cells ; cytology ; metabolism ; Humans ; Immunosuppression ; Immunosuppressive Agents ; therapeutic use ; Male ; Middle Aged ; Young Adult

OBJECTIVETo analyze the characteristics of acquired pure red cell aplasia (PRCA) secondary to T cell large granular lymphocyte leukemia (T-LGLL).

METHODSFourteen patients with T-LGLL associated with PRCA between 2000 and 2006 in our hospital were retrospectively analyzed.

RESULTSThe median age at diagnosis was 61 years with equal gender distribution. The PRCA had indolent process, mainly presenting with anemia. Of the 14 patients, 9 had mild to moderate splenomegaly, one hepatomegaly and one lymphadenopathy. The median Hb level was 61.5 g/L and the median WBC count 4.3 x 10(9)/L. The median percentage and count of LGL in peripheral blood were 0.36 and 1.9 x 10(9)/L respectively. The median percentage of LGL in BM was 0.165 (0.085 - 0.410). Some patients had serologic abnormalities. All the 12 cases with available bone marrow cell cytogenetics showed normal karyotypes. With cyclosporine A or glucocorticoid immunosuppressive therapy, the overall response was 91%.

CONCLUSIONT-LGLL was one of the major causes of acquired PRCA. This type of PRCA has the similar clinical and laboratory feature to that of other type of PRCA and has a good response to immunosuppressive therapy.

Adult ; Aged ; Female ; Humans ; Leukemia, Large Granular Lymphocytic ; complications ; Male ; Middle Aged ; Red-Cell Aplasia, Pure ; complications ; Retrospective Studies

OBJECTIVETo study the bone marrow microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression and their clinical significance in patients with aplastic anemia (AA).

METHODSBone marrow biopsies in 51 newly diagnosed patients with AA were evaluated the MVD and VEGF expression by immunostaining with anti-factor VIII related antigen and VEGF monoclonal antibodies at regular time points after immunosuppressive therapy (IT).

RESULTSThe mean bone marrow MVD in AA group was 5.5 +/- 3.5, being significantly lower than that in normal control group (8.7 +/- 3.4, P < 0.05). MVDs of SAA and NSAA patients were 7.4 +/- 2.9 and 4.3 +/- 3.4, respectively, being significantly different (P < 0.01). The VEGF expression in AA group was significantly lower than that in control group [(6.7 +/- 8.4)% vs (14.7 +/- 6.1)%, P < 0.01], but there was no difference between SAA and NSAA. Bone marrow MVD and VEGF were significantly increased after IT in 22 responded AA patients.

CONCLUSIONBone marrow MVD and VEGF expression are low in AA patients which may be one of pathophysiologic mechanisms of bone marrow failure in AA. Proangiogenic and ameliorating microcirculation agents together with IT might accelerate the recovery of hematopoiesis in AA patients.

Adolescent ; Adult ; Anemia, Aplastic ; metabolism ; pathology ; Bone Marrow ; blood supply ; metabolism ; Child ; Female ; Humans ; Male ; Microvessels ; pathology ; Middle Aged ; Neovascularization, Pathologic ; Vascular Endothelial Growth Factor A ; metabolism