OBJECTIVETo investigate the frequency and type of PHEX gene mutations in children with X-linked hypophosphatemic rickets (XLH), the possible presence of mutational hot spots, and the relationship between genotype and clinical phenotype.

METHODSClinical data of 10 children with XLH was retrospectively reviewed. The relationship between gene mutation type and severity of XLH was evaluated.

RESULTSPHEX gene mutations were detected in all 10 children with XLH, including 6 cases of missense mutation, 2 cases of splice site mutation, 1 case of frameshift mutation, and 1 case of nonsense mutation. Two new mutations, c.2048T>C and IVS14+1delAG, were found. The type of PHEX gene mutation was not associated with the degree of short stature and leg deformity (P=0.571 and 0.467), and the mutation site was also not associated with the degree of short stature and leg deformity (P=0.400 and 1.000).

CONCLUSIONSMissense mutation is the most common type of PHEX gene mutation in children with XLH, and c.2048T>C and IVS14+1delAG are two new PHEX gene mutations. The type and site of PHEX gene mutation are not associated with the severity of XLH.

Adolescent ; Child ; Child, Preschool ; Familial Hypophosphatemic Rickets ; genetics ; Female ; Humans ; Infant ; Male ; Mutation ; PHEX Phosphate Regulating Neutral Endopeptidase ; genetics ; Retrospective Studies

China ; Cost of Illness ; Demography ; Female ; Humans ; Maternal Mortality ; Poverty Areas

Objective To explore inhibition of amlodipine on myocar-dial cell injury induced by ischemia reperfusion .Methods Thirty Wistar rats were randomly into three groups: sham operation group ( n =10 ) , model group group ( n =10 ) , test group ( 2 mg? kg -1 amlodipine , n=10).The model group and test group were made by ligation of left anterior descending coronary artery to make the model of myocardial ischemia reperfusion.Rats in each group were administered 7 d before ligation.Cell apoptosis was examed by flow dual staining method .The activity of cysteinyl aspartate specific proteinase 3 ( Caspase 3 ) was measured by spectrophotometry .The activation of phosphatidylinositol 3 kinase ( PI3K)/protein kinase B ( AKT) signalling pathway, B-cell lymphoma-2 ( Bcl-2 ) , Bcl-2 associated X protein ( Bax ) were assayed by Western blot .Results Compared to sham operation group on early and late myocardial cell apoptosis , myocardial cell apoptosis with ( 2.34 ±0.35 )%, (3.58 ±0.39 )%, that on early and late myocardial cell apoptosis were increased with ( 15.69 ±1.14 )%, (24.74 ±2.56)%in model group ( P <0.05 ) .Compared to sham operation group on the activity of Bax with (0.18 ±0.01) and Caspase 3 activity with (1.00 ±0.10), the expression of Bax express with (0.62 ±0.06) and Caspase 3 activity with (3.98 ±0.18) in model group were increased (P<0.05).Compared to sham operation group on the expre-ssion of Bcl-2 with (0.99 ±0.10 ) and expression of PI3K with (0.89 ±0.06 ), on the expression of Bcl-2 with (0.14 ±0.01) and expression of PI3K with (0.18 ±0.01) in model group were decreased (P<0.05). Compared to sham operation group on phosphorylation of AKT with ( 0.95 ±0.10 ) , the phosphorylation of AKT in model group with (0.13 ±0.01 ) was decreased ( P<0.05 ).Compared with model group , test group could change the variation on the early and late myocardial cell apoptosis with ( 5.23 ±0.13 )%, ( 8.09 ±0.35 )% while on the Caspase 3 activity with ( 1.47 ±0.14 ) ( P<0.05 ) .Conclusion These results suggested that amlodipine inhibited myocardial ischemia reperfusion injury, which was related to activition PI3K/AKT signal pathway.

OBJECTIVETo analyze the effect of sorafenib as salvage therapy used before and/or after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in refractory relapsed FLT3-positive acute myeloid leukemia (AML).

METHODSA total of 16 patients with refractory relapsed FLT3-positive AML, including 10 refractory relapsed pre-transplantation and 6 relapsed after allo-HSCT, were enrolled in this retrospective study. Sorafenib treatment protocols included sorafenib in combination with chemotherapy inducing remission, and sorafenib monotherapy as mauntenance treatment after complete remission (CR).

RESULTSThirteen of the 16 patients achieved CR after one or two courses of induction therapy, including 7 refractory relapsed pre-transplantation and 6 relapsed after allo-HSCT. With a median follow up of 472 (range, 59-1569) days post-transplantation, 12 patients survived and 4 died. Causes of death included leukemia relapse (n=3) and acute graft-versus-host disease (n=1). The 2-year overall and disease-free survival post-transplantation of the 16 patients were (75.0±10.8) % and (50.5±13.7) % respectively. The main side effect of sorafenib was the skin rash. The incidence of rash was lower in the patients used sorafenib pre-transplantation than those post-transplantation (30.0% vs 75.0%, P=0.043).

CONCLUSIONSorafenib used as salvage therapy befor and/or after transplantation for refractory relapsed FLT3-positive AML could reduce the relapse rate and improve the survival.

Antineoplastic Agents ; therapeutic use ; Disease-Free Survival ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; genetics ; therapy ; Mutation ; Niacinamide ; analogs & derivatives ; therapeutic use ; Phenylurea Compounds ; therapeutic use ; Recurrence ; Remission Induction ; Retrospective Studies ; Salvage Therapy ; Treatment Outcome ; fms-Like Tyrosine Kinase 3 ; genetics

OBJECTIVETo analyze mutation types, clinical features, and treatment outcomes of cobalamin C (cblC) type combined methylmalonic aciduria and homocystinuria (MMA-HC) and to investigate the relationship of genotypes with clinical phenotypes and outcomes.

METHODSThe clinical data of 16 Chinese children diagnosed with cblC type MMA-HC by gene analysis were retrospectively analyzed. According to the onset age, the patients were classified into early onset (≤1 year) and late onset (>1 year). According to the clinical phenotype, the patients were classified into mild, moderate, and severe groups. All the patients were treated with vitamin B12 (cyanocobalamin) or hydroxocobalamin, betaine, folate, vitamin B6, and L-carnitine.

RESULTSFifteen patients belonged to the early onset type, including 11 in the severe group and 4 in the moderate group. The remaining one belonged to the late onset type. Seven reported mutations and two novel mutations (c.445_446delTG and c.349G>c) were detected. The c.609G>A and c.658_660delAAG were the most common mutations detected in 13 (81%) out of 16 patients. The genotype caused by compound heterozygous mutations of these two alleles (c.609 G>A/c.658_660delAAG) was the most common in the patients, detected in 4 (25%) out of 16 patients. Patients with this genotype had severe microcephaly and eye diseases and these clinical manifestations were not improved after the treatment. The patient with late-onset cblC type MMA-HC had normal clinical phenotypes after treatment. In the 15 early onset patients, the more severe the clinical phenotype, the worse the treatment outcome.

CONCLUSIONSThe cblC type MMA-HC mainly manifests as early onset in China and c.609G >A and c.658_660delAAG are the most common mutations causing this disease. The clinical phenotypes are associated with the outcomes in children with cblC type MMA-HC.

Child ; Child, Preschool ; Female ; Genotype ; Homocystinuria ; genetics ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation ; Phenotype ; Vitamin B 12 Deficiency ; congenital ; genetics

This study was aimed to evaluate the proliferation-associated antigen Ki-67 expression in diffuse large B cell lymphoma (DLBCL) and its clinical significance. The Ki-67 expression and its correlation with prognosis in 50 patients with DLBCL treated with rituximab plus CHOP (R-CHOP) between January 2008 and December 2010 were analyzed retrospectively. The results indicated that there was no significant relationship between Ki-67 expression and clinical features, including age, sex, staging, B symptoms, LDH level, IPI, extranodal site involvement, presence of bulky tumors (>10 cm in diameter), bone marrow involvement, GCG nor GCB type, or response to first line treatment. The median survival was 50 months and 15 months in low Ki-67 expression group (<85%) and in high Ki-67 expression group ( ≥ 85%) respectively. The overall survival (OS) and progress-free survival (PFS) in low Ki-67 expression group were obviously longer than that in high Ki-67 expression group (P = 0.001; P = 0.027). In univariate analysis, the clinical factors associated with OS included Ann Arbor staging and Ki-67 expression. The clinical factors associated with PFS included Ann Arbor staging. IPI and Ki-67 expression. In multivariate analysis. The Ki-67 expression level was an independent prognostic factor for OS (HR = 4.90; 95% CI, 1.456-16.511; P = 0.0103). It is concluded that Ki-67 expression level seems to be an effective marker for evaluation of DLBCL prognosis.
Adult ; Aged ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Humans ; Ki-67 Antigen ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; metabolism ; pathology ; Male ; Middle Aged ; Prednisone ; therapeutic use ; Prognosis ; Retrospective Studies ; Vincristine ; therapeutic use ; Young Adult

Objective To investigate the prevalence, common clinical symptoms and complications, transmission routes and media of brucellosis among human in the city of Songyuan in Jilin province, and to provide practical basis for brucellosis intervention and related control measures. Methods Use self-designed questionnaire to collect information from outpatients in brucellosis clinic in Songyuan Center for Disease Control and Prevention from January to June 2009, and to analyze the related data from the survey: prevalence, time and geographical distribution, clinical symptom, transmission route and media. Results Of the total 620 cases investigated, there were 284 patients accounting for 45.8% (284/620), 75 suspected patients accounting for 12.1% (75/620), 13stealth patients accounting for 2.1% (13/620) and 248 negative people accounting for 40.0% (248/640). Main common symptoms of the patients were fever[66.5%( 189/284)], muscle and joint pain[38.7%( 110/284)],fatigue[27.5%(78/284)], hyperhidrosis[25.0%(71/284)]and low back pain[17.3%(49/284)]. The patients group had a significantly higher prevalence of mucocutaneous infection, contacting infected animal abortion flow,fur, soil, faeces and dust than the uninfected group(χ2 value were 27.12, 22.75, 8.90, 6.65, 6.39, 6.39, all P< 0.01 or < 0.05). Conclusions The positive rate of brucellosis in the brucellosis clinic of Songyuan city is high,and patients have typical symptoms. We should take comprehensive control measures to protect the high-risk group and reduce the local infectivety.

OBJECTIVETo investigate the therapeutic effect of infrared radiation (IR) on the skin scald in rats.

METHODSThirty-nine male Wistar rats were used in the study, and they were randomly divided into normal control (C, n = 13), scald (S, n = 13, no treatment after scalding) and treatment (T, n = 13, with IR radiation treatment for 5 days since 2nd post scalding day (PSD) groups. The rats in S and T groups were subjected to deep partial thickness scalding on the back. The cutaneous tissue samples from rat wound in each group were harvested on the 3rd and 7th PSD for pathomorphological examination. DNA synthesis in wound tissue was analyzed by 3H-TdR incorporation method, and the vascular permeability in cutaneous tissue, degree of tissue edema and MDA content were determined by corresponding methods.

RESULTSEpidermal exfoliation, cutaneous ulcer, follicular atrophy and damage, and massive formation of collagen were identified in the skin wound of rats in S group on the 7th PSD compared with C group. The skin in T group was smooth with slight atrophy and a few collagen fibers in follicles. The 3H-TdR incorporation amount in the rats in T group (1856.33 +/- 343.81 cpm/mg) on the 7th PSD was significantly higher than that in S group (1353.95 +/- 274.48 cpm/mg) (P < 0.01). The tissue permeability, edema degree and MDA content in the cutaneous tissue in S group were obviously higher than those in group C, while these indices were markedly lower in T group when compared with those in S group (P < 0.01-0.001).

CONCLUSIONTreatment with IR seemed to be beneficial to the promotion of skin tissue metabolism and tissue repair.

Animals ; Burns ; metabolism ; pathology ; radiotherapy ; Infrared Rays ; therapeutic use ; Male ; Malondialdehyde ; analysis ; Rats ; Rats, Wistar

Chuangxinmycin (CM) from Actinoplanes tsinanensis was an antibiotic discovered by Chinese scientists about 40 years ago. It contains a new heterocyclic system of indole fused with dihydrothiopyran, whose biosynthetic mechanism remains unclear. CM is used as an oral medicine in the treatment of bacterial infections in China. The simple structure makes CM as an attractive candidate of structure modification for improvement of antibacterial activity. Recently, we analyzed the secondary metabolites of Actinoplanes tsinanensis CPCC 200056, a CM producing strain, as a natural CM analogue. We discovered the first natural CM analogue 3-demethylchuangxinmycin (DCM) as a new natural product. Compared to CM, DCM exhibited a much weaker activity in the inhibition of the bacterial strains tested. The finding provides valuable information for the structure-activity relationship in the biosynthesis of CM.
Anti-Bacterial Agents ; chemistry ; isolation & purification ; China ; Indoles ; chemistry ; isolation & purification ; Micromonosporaceae ; chemistry ; Structure-Activity Relationship

Objective: To observe the blood perfusion volume variation pattern in the body surface microcirculation at the Yuan-Primary and the Xi-Cleft points during the menstrual cycle in female college students with moderate constitution under normal physiological state of the uterus; to explore the specific laws of the body surface microcirculation at the Yuan-Primary and Xi-Cleft points in response to the uterine qi and blood changes under normal physiological conditions, and to provide the experimental basis for the specificity of acupoints reflecting the uterine function. Methods: Forty-three healthy and moderate constitution female college students with regular menstrual cycles, without dysmenorrhea and not yet giving birth were recruited. Bilateral Yuan-Primary points [Taichong (LR 3), Taibai (SP 3) and Taixi (KI 3)] and Xi-Cleft points [Zhongdu (LR 6), Diji (SP 8) and Shuiquan (KI 5)], belonging to the three yin meridians of foot and adjacent to the spinal cord segment of the uterus, were selected as the detection acupoints; the crossing point of the three yin meridians of foot [Sanyinjiao (SP 6)], the uterus-related meridian acupoint [Xuehai (SP 10)], the uterus-non-related meridian acupoint [Xuanzhong (GB 39)], and the non-meridian non-acupoint point were selected as the control points. The laser speckle blood flow imaging technique was used to monitor the blood perfusion volume in skin microcirculation at the above points at the menstrual, follicular, ovulatory, and luteal phases of the subjects. Results: The blood perfusion volume in the body surface microcirculation at the right Zhongdu (LR 6) at the ovulatory phase was higher than that at the menstrual, follicular and luteal phases (all P<0.05); there was no significant difference in the microcirculation blood perfusion volume at the other points among different phases (all P>0.05). Conclusion: The blood perfusion volume in the body surface microcirculation at Zhongdu (LR 6), the Xi-Cleft point of the Liver Meridian, shows a specific response to qi and blood changes in the uterus of women with moderate constitution.