Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Objective To study the effect of Febuxostat on NALP3 inflammasome in chronic gouty arthri-tis. Methods A total of 89 patients with chronic gouty arthritis and 50 healthy cases were enrolled in this study and 89 patients were divided into Benzbromarone group,Allopurinol group,Febuxostat group and placebo group. The expression of NALP3 inflammasome mRNA and the protein were detected by RT-PCR and Western blot. Re-sults The levels of Uric Acid,NALP3,ASC and caspase-1 mRNA in chronic gouty arthritis patients were higher than those in healthy cases before treatment(#P = 0.000);the level of NALP3 in benzbromarone and allopurinol group had no change after treatment(*P<0.05).The levels of NALP3 mRNA and caspase-1 mRNA in Febuxostat group were lower but the level of ASC mRNA was higher than those in other groups after treatment(*P < 0.05). Conclusions NALP3 inflammatory may be associated with chronic gouty arthritis. Febuxostat can effectively re-duce the level of Uric Acid,and affect the function of NALP3 inflammasome.

Objective To investigate the prognostic significance of extended resection for locally advanced colorectal carcinoma. Methods Clinical data of 960 cases of colorectal cancer hospitalized for surgery between Jan 1995 and Dec 2002 were reviewed, and complication rates, perioperative mortality, 5-year survival were calcualated, prognostic factors were analyzed using Cox regression model. Results Sixty-six patients with locally advanced colorectal carcinoma were treated with extended resection, accounting for 6.9% of the total cases. Surgical complication rate in this subgroup was 27.3% (18/66), relatively higher than that of conventional resection for colorectal carcinoma (?~2 =8.82, P=0.002). The perioperative mortality was zero. Pathology showed that carcinoma invasion into the adjacent organs resected en bloc was 31% (27/88), the 5-year survival rate was 62%. The tumor spreading into the adjacent organ (Wald=7.42,P=0.005) and lymph node status (Wald=4.55, P=0.035) were found to be the independent prognostic factors. Conclusions Extended resection for locally advanced colorectal carcinoma resulted in a favorable prognosis. Postoperative complication was relatively high, but still acceptable.