OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected by glycogen storage disease (GSD) type Ia with gout as the first manifestation. METHODS: Clinical and biochemical data of the pedigree were collected. Available members of the pedigree were subjected to gene sequencing, and the result was analyzed by bioinformatics software. The pedigree was followed up for five years. RESULTS: The proband was a young female manifesting recurrent gout flare, hypoglycemia, and hypertriglyceridemia. One of her younger brothers also presented with dysplasia and hepatic adenoma. Gene sequencing revealed that the proband and her younger brother both harbored c.1022T>A (p.I1e341Asn) and c.230+5G>A compound heterozygous variants of the G6PC gene , which were inherited from their father and mother, respectively. Among these, the c.230+5G>A is an intron region variant which was unreported previously, and bioinformatics analysis showed that it may impact mRNA splicing of the gene. The proband was treated with raw corn starch, allopurinol, and fenofibrate. Gout was well controlled, and she had given birth to a baby girl without GSD. CONCLUSION GSD Ia should be considered among young gout patients with hypoglycemia and hepatomegaly, for which gene sequencing is warranted. GSD Ia has a good prognosis after comprehensive treatment with diet and medicine.
China ; Female ; Glycogen Storage Disease Type I ; Gout/genetics* ; Humans ; Hypoglycemia ; Male ; Pedigree ; Symptom Flare Up

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 improve the awareness of cholesterol crystal embolism syndrome (CCE) inrheumatologists.Methods:The clinical characteristics of 40 Chinese CCE patients admitted to our department (one case) were summarize and in the literature (thirty-nine cases) were reviewed.Results:Among these 40 patients, 87.5%(35/40) were male and the mean age was (68±6) years. All patients suffered from athero-sclerosis and 87.5%(35/40) of them had precipitating factors such as endovascular intervention, vascular surgery, anticoagulant, or thrombolytic therapy. The clinical manifestations included renal insufficiency (90.0%, 36/40), blue toe syndrome (82.5%, 33/40), ulceration or gangrene (25.0%, 10/40), and livedo reticularis (15%, 6/40). Acute phase reactant was tested in 25 cases, of whom 84.0%(21/25) showed elevated C-reactive protein (CRP) and 56.0%(14/25) showed elevated erythrocyte sedimentation rate (ESR).Conclusion:Rheumatologists should be alert that CCE is one of the differential diagnosis of systemic vasculitis, especially for patients with severe atherosclerosis.

Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.

【Objective】To explore clinical manifestations and features of renal uric acid excretion in gout patients with obesity.【Methods】Totally 228 primary gout patients were enrolled and divided into three groups according to body mass index（BMI）. Clinical and fasting blood biochemical analysis data were collected. Indices of renal uric acid excretion were calculated according to 24 h urinary uric acid and urinary creatinine.【Results】The obese group（n = 44）was younger than overweight group（n = 88）and non-overweight group（n = 96）［43（32，57）years vs 55（45，65）years，58（45，67）years］，with earlier onset age［37（26，48）years vs 48（38，59）years］，higher serum uric acid［594（522，697）μmol/L vs 511（372，653）μmol/L］and had more hypercholesterolemia（56.8% vs 31.3%）and low density lipoproteinemia（59.1% vs 47.9%）compared with non-overweight group. The ratio of hypertriglyceridemia（43.5% and 37.5% vs 17.7%）and metabolic syndrome（50.0% and 36.4% vs 12.5%）in the overweight and obese group were both higher than non- overweight group. Fraction excretion of uric acid（FEUA）in obese group［5.5（3.6，7.4）% vs 7.0（5.2，9.8）%］was lower than non-overweight group，and the glomerular filtration load of uric acid［5.3（4.2，7.5）mg·min- 1 ·1.73 m- 2 vs 3.5（2.2，5.2）mg·min-1·1.73 m-2］in obese group was higher than that in non-overweight group（All P < 0.0167）. Multivariate regression analysis showed that overweight or obesity were negatively correlated with FEUA（All P < 0.05）.【Conclusion】High uric acid load of serum and glomerular filtration in gout patients with obesity may be due to the relative insufficiency of renal uric acid excretion.

Phytochemical investigation of the leaves and twigs of Callicarpa cathayana led to the isolation of six new clerodane diterpenoids, cathayanalactones A-F (1-6), together with seven analogues (7-13). Their structures were established by extensive NMR analyses together with experimental and calculated ECD spectra analyses. Compounds 1, 2, 3, 7 and 11 showed inhibitory activities on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells.

Objective To investigate clinical characteristics and renal uric acid excretion in early-onset gout patients.Methods Consecutive inpatients with primary gout were recruited between 2013 and 2017.The patients with gout onset younger than 30 were defined as early-onset group while the others were enrolled as control group.Clinical characteristics and uric acid (UA) indicators were compared between two groups.Results Among 202 recruited patients,the early-onset group included 36 patients (17.8％).Compared with control group,the early-onset group presented more patients with obesity [13 patients (36.1％) vs.22 patients (13.3％),P＜0.05],significantly higher serum UA level [(634± 124)μmol/L vs.(527± 169).μmol/L] and glomerular load of UA[(7.2±2.8)mg· min-1 · 1.73m-2 vs.(4.4±2.2)mg· min-1 · 1.73m-2] and estimated glomerular filtration rate (GFR) [(83±21)ml· min-1 · 1.73m-2 vs.(67±21)ml· min-1 · 1.73m-2] (all P＜ 0.05),lower fractional excretion of UA [4.4％ (3.4％,6.1％) vs.7.2％ (5.2％,9.6％),P＜0.05],whereas 24h urinary UA excretion was comparable [(2 788±882)l,μmol/1.73m2 vs.(2 645±1 140)μmol/1.73m2,P=0.274].Subgroup analysis of patients without chronic kidney disease showed significantly lower fractional excretion of UA in the early-onset group [4.5％(3.3％,6.1％) vs.6.7％ (5.1％,8.7％),P＜0.05].Logistic regression analysis showed that obesity (OR=3.25) and fractional excretion of UA less than 7％ (OR=9.01,all P＜0.05) were risk factors of gout early onset.Conclusion The gout patients with early-onset younger than 30 present high serum and glomerular load of uric acid which might be due to obesity and relative under-excretion of renal uric acid.

AIM: To investigate the effects of rosiglitazone on fibroblast-like synoviocyte ( FLS )-induced osteoclastogenesis in rheumatoid arthritis ( RA) and the related mechanism.METHODS: RA-FLS were cocultured with peripheral blood monocytes from healthy volunteers in the presence of macrophage colony-stimulating factor ( M-CSF) and rosiglitazone.Osteoclasts were assayed by tartrate-resistant acid phosphatase ( TRAP) staining.Resorption lacunae area was identified by toluidine blue staining and quantified by image analysis software.The mRNA expression of RANKL and OPG was evaluated by real-time PCR, and the protein levels of RANKL, OPG, p-ERK, p-p38 and p-JNK were measured by Western blot.RESULTS:Compared with control group ( without rosiglitazone treatment) , rosiglitazone at concentration of 15 μmol/L significantly decreased the number of osteoclasts (P<0.01) and resorption lacunae area (P<0.05).The expression of RANKL at mRNA and protein levels was significantly down-regulated by rosiglitazone at concentration of 15μmol/L, while the mRNA and protein expression of OPG was up-regulated (P<0.01).Rosiglitazone (15 μmol/L) sig-nificantly decreased the protein level of p-ERK ( P<0.05 ) , but not the protein level of p-p38 or p-JNK ( P>0.05 ) . CONCLUSION:Rosiglitazone inhibits RA-FLS-induced osteoclast formation and its resorption activity by down-regulating RANKL expression and ERK phosphorylation, suggesting that rosiglitazone may inhibit RA osteoclastogenesis and bone re-sorption.

Objective To observe the efficacy and safety of tocilizumab on patients with refractory rheumatoid arthritis (RA).Methods Eighteen RA patients who were refractory to disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor-α (TNF-α) antagonist were treated with tocilizumab were included into this study.Their clinical disease activity indices,Hospital Anxiety and Depression Scale (HADS)and safety were evaluated regularly.Statistical analysis was conducted with Mann-Whitney U test and x2 test.Results According to clinical disease activity index,44％(8/18) of patients reached treatment target 2 weeks after the first infusion of tocilizumab,and 78％ (14/18) reached treatment target after three infusions of tocilizumab.Fifty-six percent (10/18) of patients had anxiety and 22％ (4/18) had depressive symptoms at baseline.After three infusions of tocilizumab,6％(1/18) had anxiety symptoms and 11％(2/18) had depressive symptoms.The adverse effects included upper respiratory tract infection,aminotransferase elevation and neutropenia (3 patients,respectively).Conclusion Tocilizumab can rapidly and significantly improve the disease activity and psychological state with good tolerance and safety,which can be applied to Chinese refractory RA patients who failed with DMARDs or TNF-α antagonist.

Objective To investigate the dynamic expression and significance of B cell lymphoma (Bcl) 6 in fibroblast-like synoviocytes (FLS) induced osteoclast differentiation and activation in rheumatoid arthritis (RA) patients.Methods RA-FLS were co-cultured with peripheral blood monocytes (PBMCs) from healthy volunteers in the medium containing M-CSF.Bcl6 protein and mRNA in osteoclasts and their precursors were determined by immunofluorescence and Real-time PCR at day 0,7,14 and 21,respectively.Osteoclasts were identified by tartrate-resistant acid phosphatase (TRAP) staining.Bone resorption activity of osteoclasts was determined by bone slices stained with toluidine blue.Kruskal-Wallis H and Bonferroni were used for statistical analysis.Results ① Immunofluorescence staining and TRAP staining showed that Bcl6 protein was mainly expressed in the nuclei of PBMCs.After co-cultured with RA-FLS for 7 days,some PBMCs differentiated into macrophages and a few differentiated to TRAP-positive multinucleated osteoclasts,and the total Bcl6 protein expression in osteoclasts and their precursors were increased.At day 14,the total Bcl6 protein expression was increased further.At day 21,the Bcl6 protein expression in nuclei of osteoclasts was decreased while PBMCs were differentiated into osteoclasts,and total Bcl6 protein expression was decreased.②Real-time PCR showed that Bcl6 mRNA expression in osteoclasts and their precursors at day 7 tended to increase than that at day 0 (x2=3.429,P＞0.05).At day 14 after co-cultured with RA-FLS,Bcl6 mRNA expression in osteoclasts and their precursors was significantly higher than that at day 0 (x2=5.333,P=0.045).At day 21,the expression of Bcl6 mRNA was significantly lower than that at day 14 (x2=6.023,P=0.038).Conclusion Bcl6 may be involved in osteoclast differentiation and activation,and may play a role in the inflammatory status in the process of differentiation from PBMCs to macrophages.Further studies are needed to establish the mechanisms.