Evaluating the effect of methotrexate on the rate of renal fibrosis by elastography and fibrosis-related gene expression.

Methotrexate is mainly used to treat diseases such as rheumatoid arthritis (RA), but its potential for nephrotoxicity has always been a significant concern on the use of this medication. This study aimed to determine the rate of renal fibrosis using transient elastography and its relationship with cumulative dose and duration of drug use in patients with rheumatoid arthritis treated with methotrexate. TGFß gene expression was also assessed for further evaluation. Patients with rheumatoid arthritis who received methotrexate for more than six months were included. Renal fibrosis was determined by measuring the stiffness of the kidney by elastography (FiberScan Device). RA patients were divided into two groups based on kidney stiffness measurement with and without renal fibrosis, and demographic, clinical, and biochemical parameters were compared to investigate the relationship between cumulative dose and duration of methotrexate treatment and renal fibrosis. Also, in this study, 50 controls (healthy people) and 50 cases (RA patients) were used to evaluate the expression of the TGFß gene by real-time PCR method. The existence of kidney fibrosis was observed in 10 patients. There was no significant relationship between renal fibrosis and the cumulative dose (P = 0.21) and duration of methotrexate (P = 0.30). Multivariate regression analysis showed that the chances of developing renal fibrosis in patients increase with increasing serum ALT levels (P = 0.01). The results of the TGFß gene expression showed that the expression of this gene in the group of RA patients with fibrosis was higher than the control group (healthy people) and the group of RA patients without fibrosis (P <0.01). These results showed that evaluation of renal fibrosis by elastography method is recommended for scanning RA patients while they are being treated with methotrexate, which is also confirmed by the results of the fibrosis-related-gene expression.

Altered Functional Connectivity Between the Cerebellum and the Cortico-Striato-Thalamo-Cortical Circuit in Obsessive-Compulsive Disorder.

Background: Altered resting-state functional connectivity of the cerebellum in obsessive-compulsive disorder (OCD) has been previously reported. However, the previous study investigating cerebellar-cerebral functional connectivity relied on a priori-defined seeds from specific networks. In this study, we aimed to explore the connectivity alterations of the cerebellum in OCD under resting-state conditions with a hypothesis-free approach. Methods: Thirty patients with OCD and 26 healthy controls (HCs) underwent functional magnetic resonance imaging (fMRI) scanning at resting state. Regional cerebral function was evaluated by measuring the fraction of amplitude of low-frequency fluctuation (fALFF). Regions with mean fALFF (mfALFF) alterations were used as seeds in seed correlation analysis (SCA). An independent samples t test was used to compare the differences in mfALFF and functional connection (FC) between the two groups. Pearson correlation analysis was performed to identify the association between functional neural correlates and OCD symptom severity evaluated using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Results: Compared with the HC group, the OCD group showed significantly increased mfALFF values in bilateral cerebellar. The results of FC analysis showed weakened connectivity among the left Crus II, lobule VIII, and right striatum and between the right lobule VIII and the right striatum, and cingulate in the OCD group compared with the HC group. Some of the abovementioned results were associated with symptom severity. Conclusions: OCD patients showed abnormal spontaneous cerebellar activity and weakened functional connectivity between the cerebellum and the cortico-striato-thalamo-cortical (CSTC) circuit (striatum and cingulate), suggesting that the cerebellum may play an essential role in the pathophysiology of OCD.

[The lipid peroxidation mechanism initiated by ischemia-reperfusion injury during renal transplantation].

OBJECTIVE: To explore the mechanism of acute ischemia-reperfusion injury (IRI) to renal-transplant METHODS: A total of 12 Chinese Sichuan White Pigs (SWPs) (2-3 months old, 17.5 +/- 4.6 kg, with clear family background) were used. 3 pairs of them with better tissue typing were subjected to renal allotransplantation. The other SWPs were allocated to renal autotransplantation. We assessed the SWPs' kidney function, serum superoxide dismutase (SOD) and malonaldehyde (MDA) after transplantation so as to shed light on the possible mechanism of IRI and to find out good detecting methods which could monitor IRI. RESULTS: Serum creatinine and urea increased in 2 days of postoperation and then returned to normal in both groups except the pigs that suffered from acute tubular necrosis or acute rejection. The concentrations of serum MDA and SOD began to increase 2 days after operation (P < 0.05). More increase of serum MDA and less increase of SOD were detected in renal allotransplant groups than in renal autotransplant groups (P < 0.05). The concentration of serum SOD and MDA were correlated (r = 0.961). CONCLUSION: IRI could initiate lipid peroxidation. IRI could be a single factor or be synergistic with immunologic factors to injure the transplanted organs.