Objective To establish a transgenic mouse model of facioscapulohumeral muscular dystrophy(FSHD)using tamoxifen induction and Myf6-CreERT2 and FLExDUX4 mice.Methods Dual transgenic(M6D4/+)mice were generated by crossbreeding Myf6-CreERT2 hemizygous and FLExDUX4 hemizygous mice.Full-length DUX4(DUX4-fl)expression was induced by tamoxifen starting at 3 weeks old.The disease model was evaluated at 9 weeks old by assessing changes in body mass,four-limb strength,inverted screen test,skeletal muscle weight ratio,hematoxylin/eosin,Picrosirius Red,and immunofluorescent staining of skeletal muscle paraffin sections,quantitative real-time polymerase chain reaction(RT-PCR),and RNA-sequencing(RNA-seq)of skeletal muscle.Results Dual transgenic heterozygous mice(M6D4/+)were successfully obtained.These mice exhibited significant physiological and pathological changes at 9 weeks,including delayed weight gain,reduced four-limb strength and endurance,decreased skeletal muscle weight ratio,and increases in centrally nucleated muscle fibers and fibrosis.Expression levels of DUX4 and its targeted genes were significantly up-regulated in skeletal muscle,as demonstrated by RT-PCR.RNA-seq revealed up-regulation of immune regulation-,interleukin-6,and tumor necrosis factor-related genes and down-regulation of skeletal muscle development-and differentiation-related genes.Conclusions M6D4/+mice effectively simulated the skeletal muscle phenotype of FSHD and thus provide a good animal model for research into the pathogenesis,intervention,and treatment of FSHD.

Objective To establish a transgenic mouse model of facioscapulohumeral muscular dystrophy(FSHD)using tamoxifen induction and Myf6-CreERT2 and FLExDUX4 mice.Methods Dual transgenic(M6D4/+)mice were generated by crossbreeding Myf6-CreERT2 hemizygous and FLExDUX4 hemizygous mice.Full-length DUX4(DUX4-fl)expression was induced by tamoxifen starting at 3 weeks old.The disease model was evaluated at 9 weeks old by assessing changes in body mass,four-limb strength,inverted screen test,skeletal muscle weight ratio,hematoxylin/eosin,Picrosirius Red,and immunofluorescent staining of skeletal muscle paraffin sections,quantitative real-time polymerase chain reaction(RT-PCR),and RNA-sequencing(RNA-seq)of skeletal muscle.Results Dual transgenic heterozygous mice(M6D4/+)were successfully obtained.These mice exhibited significant physiological and pathological changes at 9 weeks,including delayed weight gain,reduced four-limb strength and endurance,decreased skeletal muscle weight ratio,and increases in centrally nucleated muscle fibers and fibrosis.Expression levels of DUX4 and its targeted genes were significantly up-regulated in skeletal muscle,as demonstrated by RT-PCR.RNA-seq revealed up-regulation of immune regulation-,interleukin-6,and tumor necrosis factor-related genes and down-regulation of skeletal muscle development-and differentiation-related genes.Conclusions M6D4/+mice effectively simulated the skeletal muscle phenotype of FSHD and thus provide a good animal model for research into the pathogenesis,intervention,and treatment of FSHD.

The effects of mangiferin on uric acid excretion, kidney function and related renal transporters were investigated in hyperuricemic mice induced by potassium oxonate. Mice were divided into normal control group, and 5 hyperuricemic groups with model control, 50, 100, and 200 mg x kg(-1) mangiferin, and 5 mg x kg(-1) allopurinol. Mice were administered by gavage once daily with 250 mg x kg(-1) potassium oxonate for seven consecutive days to create the model. And 3 doses of mangiferin were orally initiated on the day 1 h after potassium oxonate was given, separately. Serum uric acid, creatinine and urea nitrogon levels, as well as urinary uric acid creatinine levels were measured. Mouse uromodulin (mUMOD) levels in serum, urine and kidney were determined by ELISA method. The mRNA and protein levels of related renal transporters were assayed by RT-PCR and Western blotting methods, respectively. Compared to model group, mangiferin significantly reduced serum uric acid, creatinine and urea nitrogon levels, increased 24 h uric acid and creatinine excretion, and fractional excretion of uric acid in hyperuricemic mice, exhibiting uric acid excretion enhancement and kidney function improvement. Mangiferin was found to down-regulate mRNA and protein levels of urate transporter 1 (mURAT1) and glucose transporter 9 (mGLUT9), as well as up-regulate organic anion transporter 1 (mOAT1) in the kidney of hyperuricemic mice. These findings suggested that mangiferin might enhance uric acid excretion and in turn reduce serum uric acid level through the decrease of uric acid reabsorption and the increase of uric acid secretion in hyperuricemic mice. Moreover, mangiferin remarkably up-regulated expression levels of renal organic cation and carnitine transporters (mOCT1, mOCT2, mOCTN1 and mOCTN2), increased urine mUMOD levels, as well as decreased serum and kidney mUMOD levels in hyperuricemic mice, which might be involved in mangiferin-mediated renal protective action.

[Objective]To evaluate the effects of Austin surgery for mild and moderate juvenile hallux valgus. [Method]From November 2005 to Januuary 2007,16 juvenile hallux valgus patients(28 feet)with average of 17.8 years(range,17 to 19 years)were treated with Austin surgery.The X-ray films of all patients were obtained before operation,and twelve months,fifteen months after operation.The hallus valgus angle,intermetatarsal angle,proximal articular set angle,and distal articular set angle were measured and analyzed on radiographs.The surgical outcome was evaluated combined with the Gu Xiang-jie's score.All pamameters were statistically analyzed. [Result]All the patients were completely followed up.Hallax valgus angle reduced from 26.3?1.19 to 11.7?0.40,intermetatarsal angle reduced from 14.1?0.82 to 7.2?0.85,proximal articular set angle from 12.7?0.28 to 6.4?0.54(all P

[Objective]To evaluate the effect of transverse arch reconstruction by modified Youngswick osteotomy on young and middle-aged hallux valgus. [Methods]From November 2005 to November 2008,25 female(36 feet) hallux valgus patients with the average age of 37.7years old(range 22 to 49 years old) were treated surgically.All feet had hypemobility of the first tarsometatarsal joint and collapse of the transverse arch of the foot.In the operation,the first metatarsal head was pushed laterally,downward and rotated downward.Modified McBride procedure was used on the correction for hallux valgus deformity.The X-ray films of all patients were obtained before operation,and 12 months after operation.The hallus valgus angle and intertatarsal angle were measured and analyzed on radiographs.The surgical outcome was evaluated combined with the Gu Xiang-jie's score.All pamameters were statistically analyzed.All cases were followed-up regularly.[Results]Twenty-one cases(28 feet) were followed-up for averaged 15.9 month.Hallax valgus angle reduced from 26.8??1.07? to 11.1??0.29?,intertatarsal angle reduced from 14.9??1.36? preoperatively to 8.3??1.19? postoperatively.The painful callus beneath the forefoot was alleviated or diminished obviously in all cases.Based on Gu Xiangjie'score,the subjective assessments were given as excellent in 16 feet,good in 7 feet,and fair in 5 feet.The good to excellent result was 82.1%.[Conclusion]For the hallux valgus with hypermobility of the first tarsometatarsal joint and transversal arch collapse,modified Youngswick surgery can recover the transverse arch,correct first metatarsal adduct abnormality,and regain the weight-bearing function of the first metatarsal head.Modified Youngswick surgery is an ideal choice for young and middle-aged hallux valgus because of less complications and reliable surgery outcomes.