Background Low doses of febuxostat or benzbromarone are widely used in Asian countries, but lacking studies to compare the efficacy and safety of the two urate-lowering drugs. Methods To compare the efficacy and safety of low-dose febuxostat with low-dose benzbromarone in patients with primary gout, a randomized controlled, open-label trial was performed among male patients with primary gout for urate-lowering therapy (ULT) in a dedicated gout clinic in China. Randomization was carried out by a third-party institution according to random number table. Patients were randomly assigned 1:1 to febuxostat group (Feb group) (20 mg daily) or benzbromarone group (Ben group) (25 mg daily) and treated for 12 weeks. General information and biochemical data were collected at baseline and at every visit monthly. Clinical characteristics before and after the ULT were analyzed in the two groups by SPSS and EmpowerStats software. Results Two hundred forty patients were enrolled and randomized in the two groups, with 214 patients completing 12 weeks’ ULT (105 in the Feb group and 109 in the Ben group). After 12 weeks, substantial percentages of patients in both Feb and Ben group achieved the target serum uric acid (sUA) (< 360 μmol/L) and serum urate levels were reduced significantly for both groups (Feb 39.5% and 156.83 μmol/L vs. Ben 35.7% and 163.99 μmol/L). Multivariate analysis suggests baseline sUA level and renal function were associated with the outcome of the rate of achieving target sUA (RAT). Sub-group analysis suggests low doses of febuxostat and benzbromarone rendered better RAT for patients with sUA < 540 μmol/L and creatinine clearance rate (Ccr) ≤ 110 mL min −1 1.73 m −2 at baseline. The drugs were well tolerated, and the incidence of gout flares in Feb group was similar with that in Ben group (22.85% vs. 33.94%). Conclusion Overall, febuxostat 20 mg daily and benzbromarone 25 mg daily reduced sUA, and gout patients with sUA level < 540 μmol/L or Ccr ≤ 110 mL min −1 1.73 m −2 at baseline had better chance to achieve target uric acid levels. The current study suggests sUA level and renal function are key factors to consider when recommending low doses of febuxostat and benzbromarone to gout patients. Trial registration Registered with ChiCTR, No. ChiCTR1800019352 (retrospectively registered).

Systemic inflammation is involved in vascular calcification and cardiovascular disease which is the leading cause of mortality in rheumatoid arthritis (RA). A high level of serum interleukin (IL)-6 plays a key role in local and systemic inflammation in RA. However, the underlying mechanisms remain unclear. We established a human umbilical artery smooth muscle cell (HUASMC) culturing method to investigate the possible role of IL-6 on vascular calcification. HUASMCs were obtained from umbilical arteries of healthy neonates. To detect calcification effects, HUASMCs were treated with (experimental group) or without (control group) recombinant human (rh) IL-6. The calcium deposition stain and calcium concentrations were measured, as well as the mRNA and protein levels of the regulating factor of osteogenic differentiation-bone morphogenetic protein (BMP) 2 and those calcifying related molecules including bone-specific alkaline phosphatase (BAP), osteoprotegerin (OPG), and osteopontin (OPN). Our study showed that rhIL-6 induced calcification of HUASMCs in a time- and dose-dependent manner, and upregulated expressions of BMP2, BAP, OPG, and OPN of HUASMCs. We then used the anti-BMP2 siRNA to knockdown the expression of endogenous BMP2 to confirm its role. HUASMCs were transfected with negative siRNA (control group) or the valid anti-BMP2 siRNA (experimental group) before they were treated with rhIL-6. Cells transfected with negative siRNA without IL-6 stimulating served as the blank group. The results showed that anti-BMP2 siRNA markedly decreased expressions of BMP2, BAP, OPG, and OPN, and also partly reduced the calcification of HUASMCs induced by rhIL-6. Collectively, according to our study, rhIL-6 could induce the extracellular calcification and osteogenic differentiation of human artery smooth muscle cells through upregulating endogenous BMP2 in vitro. This may be one of the underlying mechanisms of the overwhelming vascular calcification in RA.

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Hyperuricemia (HU) is a cause of gout. Clinical studies show a link between HU and cardiovascular disease. However, the role of soluble serum urate (SU) on atherosclerosis development remains elusive. We aimed to use a new HU mouse model [Uricase/Uox knockout (KO)] to further investigate the relationship between HU and atherosclerosis. A mouse model by perivascular collar placement of induced carotid atherosclerosis was established in male Uox‐ KO mice. The Uox‐ KO mice had elevated SU levels and enhanced levels of atherosclerosis inflammatory response proteins. In contrast, Uox‐ KO mice with carotid atherosclerosis showed severe neointimal changes in histology staining consistent with increases in intimal area and increases in proliferating cell nuclear antigen (PCNA)‐ and F4/80‐positive cells. Allopurinol reduced neointimal areas induced by the perivascular collar in hyperuricemic mice, accompanied by decreased expression of PCNA‐ and F4/80‐positive cells. Urate‐lowering treatment alleviated atherosclerosis inflammatory response factors and reactive oxygen species (ROS) intensities in both collar placement Uox‐ KO mice and urate‐stimulated human umbilical vein endothelial cells (HUVECs). In vitro results using HUVECs showed ROS was induced by urate and ROS induction was abrogated using antioxidants. These data demonstrate that urate per se does not trigger atherosclerosis intima lesions in male mice. Urate worsens carotid neointimal lesions induced by the perivascular collar and urate‐lowering therapy partially abrogates the effects. The current study warrants clinical studies on the possible benefits of urate‐lowering therapy in atherosclerosis patients with HU.

The incidence of LN-prRLN metastasis was lower than other central lymph nodes, as well as lymph nodes anterior to right recurrent laryngeal nerve. When there were multiple foci of tumors, or the tumor was larger than 1 cm, or central or lateral LN metastasis was indicated by preoperative ultrasound or confirmed by intraoperative frozen sections, it is strongly recommended that exploration and dissection of the LN-prRLN should only be performed by experienced surgeons.

BackgroundB lymphocyte hyperactivity is a main characteristic of systemic lupus erythematosus (SLE), and B lymphocytes play a prominent pathogenic role in the development and progression of SLE. The aim of this study was to investigate the role of Sirtuin 1 (Sirt1) in B lymphocytes.Material/MethodsMouse B lymphocytes BaF3 was transfected with Sirt1 vector or shRNA against Sirt1. Then the transfected cells viability and apoptosis were respectively determined by MTT assay and flow cytometry. In addition, the mRNA levels of three pro-inflammatory cytokines and p53 were detected by RT-PCR. Furthermore, the expression levels of nuclear factor-kappa B (NF-κB) pathway proteins were measured by Western blot.ResultsOverexpression of Sirt1 significantly increased cell proliferation (p<0.05 or p<0.01) and significantly suppressed apoptosis (p<0.05). The mRNA level expressions of interleukin 1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α) were significantly upregulated (p<0.05 or p<0.01), whereas p53 was significantly downregulated (p<0.05) by Sirt1 overexpression. In addition, the inhibitory subunit of NF-κB (IκBα) and p65 were significantly activated and phosphorylated (p<0.01 or p<0.001), and B-Cell CLL/Lymphoma 3 (Bcl-3) was significantly upregulated (p<0.05) by Sirt1 overexpression.ConclusionsThese results suggested that Sirt1 overexpression could promote BaF3 cell proliferation, inhibit apoptosis, and upregulate pro-inflammatory cytokines. The NF-κB pathway might be involved in these effects of Sirt1 on BaF3 cells, and Sirt1 might be a potential risk factor of SLE.

Objective: To compare the influence of breast-conserving surgery (BCS) and modified radical mastectomy (MRM) on the psychological state of breast cancer patients. Methods: Patients receiving MRM or BCS, and fulfilling the study criteria, were recruited. Patients were required to complete a self-reporting inventory (SCL-90) on admission and 6 months after surgery and a self-rating depression scale (SDS) when discharged from hospital and 6 months after surgery. Results: A total of 70 patients received MRM and 50 BCS. Compared with the national standard, patients suffered to some extent psychological problems on admission, at discharge from hospital and at 6 months after surgery. Patients received BCS had a higher score of SDS compared with those with MRM when discharged from hospital. However, 6 months after surgery, SDS score increased in MRM and decreased in the BCS group, so the difference was significant. Conclusion: The short-term psychological state of patients receiving BCS is worse than that with MRM but superior to MRM 6 months postoperatively. BCS imposed less influence on long term psychological state of breast cancer patients compared with MRM.

BackgroundIntrahepatic subcapsular hematoma (ISH) is an extremely rare, life-threatening complication after laparoscopic cholecystectomy (LC). Only few cases have been reported. Herein, we reported a rare giant ISH after LC and summarized all of the reported cases.Case presentationA 32-year old woman with recurrent acute cholecystitis for one year, underwent elective LC without intra-operative complications and was discharged 2 days after operation. On the next day after discharge, she developed severe right upper abdominal pain and was sent to our emergency department. The computed tomography scan showed a 10.9 × 12.5 × 6.6 cm ISH in the right liver without free fluid and the hemoglobin dropped to 86 g/l from 127 g/l. Postoperative hemorrhagic shock and a giant ISH after LC were diagnosed. After fluid resuscitation, the hemodynamic was still unstable and the hemoglobin kept dropping. An emergency laparoscopic exploration was performed and the ISH was confirmed, however no active bleeding point was found. A drainage tube was placed under liver for early warning of rupture. Patient was discharged home 10 days after readmission.ConclusionsGiant ISH is an extremely rare, life-threatening complication after LC. This case showed that the need to consider this rare complication in patients suffering abdominal pain after LC and timely and correct diagnosis and treatment were crucial to saving the lives of the patients.