Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c.163G>C (p.Val55Leu) mutation in FKBP5 (encodes FK506-binding protein 51, FKBP51) associated with PDB using whole-exome sequencing. Mutant FKBP51 enhanced the Akt phosphorylation and kinase activity in cells. A study of osteoclast function using FKBP51V55L KI transgenic mice proved that osteoclast precursors from FKBP51V55L mice were hyperresponsive to RANKL, and osteoclasts derived from FKBP51V55L mice displayed more intensive bone resorbing activity than did FKBP51WT controls. The osteoclast-specific molecules tartrate-resistant acid phosphatase, osteoclast-associated receptor and transcription factor NFATC1 were increased in bone marrow-derived monocyte/macrophage cells (BMMs) from FKBP51V55L mice during osteoclast differentiation. However, c-fos expression showed no significant difference in the wild-type and mutant groups. Akt phosphorylation in FKBP51V55L BMMs was elevated in response to RANKL. In contrast, IκB degradation, ERK phosphorylation and LC3II expression showed no difference in wild-type and mutant BMMs. Micro-CT analysis revealed an intensive trabecular bone resorption pattern in FKBP51V55L mice, and suspicious osteolytic bone lesions were noted in three-dimensional reconstruction of distal femurs from mutant mice. These results demonstrate that the mutant FKBP51V55L promotes osteoclastogenesis and function, which could subsequently participate in PDB development.
Acid Phosphatase ; Animals ; Asian Continental Ancestry Group ; Bone Diseases, Metabolic ; Bone Remodeling ; Bone Resorption ; Femur ; Humans ; Mice ; Mice, Transgenic ; Osteitis Deformans* ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Phosphorylation ; Phosphotransferases ; Tacrolimus Binding Proteins ; Transcription Factors

OBJECTIVE:To observe the occurrence of paclitaxel(PTX)-induced muscle soreness and therapeutic efficacy and safety of diclofenac sodium. METHODS:Among 84 patients with malignant tumor receiving PTX chemotherapy,56 patients suf-fered from PTX-induced muscle soreness,among which 22 female patients suffered from medium and severe muscle soreness and then were randomly divided into group A and B,with 11 cases in each group. Group A was given Diclofenac sodium sustained-re-lease tablet 75 mg orally,once a day;group B was given Paracetamol and tramadol hydrochloride tablets one tablet orally,once a day,and then given Promethazine hydrochloride injection 100 mg subcutaneously,2-3 times a day when muscle soreness could not be born. Treatment course of both groups lasted for 5 d. The distribution of muscle soreness were observed. The onset time and dura-tion of muscle soreness were also observed as well as pain relief and the occurrence of ADR in group A and B. RESULTS:Among 84 cases,the incidence of muscle soreness was 66.67%,among which mild pain accounted for 23.81%,moderate pain accounted for 13.10%,and severe pain accounted for 29.76%. Among 56 patients with muscle soreness,earliest muscle soreness occurred on the day of medication,and most of muscle soreness occurred on 1-3 days after medication,mainly manifesting as sore,activity limitation when severe,associated with fatigue. The pain relief rate of group A and B were 100%,but the incidence of adverse re-actions in group A was significantly lower than group B,with statistical significances(P<0.05).CONCLUSIONS:Diclofenac sodi-um is similar to paracetamol and tramadol hydrochloride in the treatment of PTX-induced muscle soreness,but it is better than paracetamol and tramadol hydrochloride in safety.

Objective: To study the compatible stability of cyclophosphamide (CTX) and Mesna admixture for injection in 4 commonly used infusions (5% glucose injection,0.9% sodium chloride injection,fructose injection and xylitol injection) at different temperatures.Methods: An HPLC method was adopted to determine the contents of CTX for injection in 24h respectively under 5℃ and 25℃.The appearance and pH value of the admixture were investigated.Results: No significant changes of appearance, pH value or content of the admixture were found out in 24h under 5℃ and 25℃.Conclusion: CTX and Mesna admixture for injection is compatible with the 4 commonly used infusions under 5℃ and 25℃ for clinical use in 24 h.

OBJECTIVE:To provide reference for perioperative rational application of antibiotics in gynecologicalⅡandⅢinci-sion surgery. METHODS:The perioperative patients of typeⅡandⅢincision surgery were collected from our hospital during Jul.-Dec. 2013-Jul.-Dec.2014,and then divided into pre-rectification group and post-rectification group. The prophylactic application of antibiotics in 2 groups were analyzed statistically. RESULTS:After rectification,rational rate of prophylactic medication in-creased from 5.38% to 89.69%(P<0.01);rational rate of prophylactic medication time increased from 11.83% to 91.75%(P<0.01);prophylactic medication duration decreased from (12 ± 2.1)d to(5.5 ± 1.9)d(P<0.01);after rectification,both total drug cost and drug cost per capita decreased significantly (P<0.01);postoperative infection rate showed no significant change before and after rectification (P>0.05). After rectification,usage and dosage of β-lactam antibiotics were in line with pharmacokinetics, Intravenous drip was adjusted from once a day to twice a day,and its rational rate increased significantly compared to before rectifi-cation(P<0.05). CONCLUSIONS:The antibiotics special rectification activities significantly promote the rationality of periopera-tive prophylactic application of antibiotics in gynaecologyⅡandⅢincision surgery of our hospital,reduce adverse drug reactions and resistant strains due to irrational use of drugs,and decrease the drug cost.

PURPOSE: SNF2L belongs to Imitation Switch family and plays an essential role in neural tissues and gonads. In our previous studies, we have demonstrated that the basal transcription of human SNF2L gene is regulated by two cis-elements, cAMP response element (CRE)- and Sp1-binding sites. Recent studies suggested that cyclic adenosine monophosphate (cAMP) stimulation significantly up-regulated SNF2L expression in ovarian granulose cells. These data suggested that protein kinase-mediated signal pathways might also regulate SNF2L expression in neural cells. We therefore investigated the effects of agents that activate protein kinases A on SNF2L gene expression in neural cells. MATERIALS AND METHODS: To increase intracellular cAMP levels, all neural cells were treated with forskolin and dbcAMP, two cAMP response activators. We exmined the effects of cAMP on the promoter activity of human SNF2L gene by luciferase reporter gene assays, and further examined the effects of cAMP on endogenous SNF2L mRNA levels by qPCR. RESULTS: Transient expression of a luciferase fusion gene under the control of the SNF2L promoter was significantly increased by treatment of rat primary neurons with forskolin or dbcAMP, but not PC12, C6 and SH-SY5Y cells. Consistently, treatment with forskolin or dbcAMP could enhance endogenous SNF2L mRNA levels also only in rat primary neurons. CONCLUSION: These results suggest that the CRE consensus sequence in the SNF2L proximal promoter most likely confers constitutive activation and regulation by cAMP in neural cells.
Animals ; Bucladesine/pharmacology ; Cell Line ; Colforsin/pharmacology ; Cyclic AMP/*metabolism ; DNA-Binding Proteins/chemistry/*genetics/metabolism ; *Gene Expression Regulation ; Humans ; Luciferases/analysis ; Neurons/*metabolism ; PC12 Cells ; Promoter Regions, Genetic ; RNA, Messenger/metabolism ; Rats ; Rats, Wistar ; Recombinant Fusion Proteins/analysis ; *Response Elements ; Transcription Factors/chemistry/*genetics/metabolism

Objective To study the frequency of cystic fibrosis transmembrane conductance regulator(CFTR)mutations in patients with congenital bilateral absence of vas deferens(CBAVD).Methods Eighty-five CBAVD patients were collected from May 2007 to May 2009.The diagnosis of CBAVD included azoospermia,normal of 4 sex hormone items,absence of seminal vesicle,normal volume of testicular and epididymis dilated siltation.And 85 normal fertile men served as controls.Genomic DNA was isolated from peripheral blood.The mutations of CFTR exons 10,11 were detected by PCR-single strand conformation polymorphism,and direct sequencing was performed on 85 cases of CBAVD and the control males.Results Of the 85 CBAVD,10 cases(11.8％)exhibited an abnormal CFTR gene mutation,with 4 cases I556V,2 cases M469V,and 1 case of E527N,A F508,L558S,S485C.No mutations were detected in 85 controls.There was a significant difference between the 2 groups(x2 =8.606,P =0.003).Conclusions CBAVD might be caused by the CFTR mutations.The frequencies and the spectrum of CFTR mutations might be different from those Caucasian population in the west country.

The theory of rough set was applied to the law of compatibility of categorized formulas research, and the decision rules model of the law of compatibility of categorized formulas was set up in order to explore the correlation between the compatibility of the categorized formula and the syndrome indexes. Based on this model, the core herbs of categorized formula were obtained through attribute reduction, the interaction of each herb in categorized formula could be analyzed by the effective decision rules, and the efficacy of the categorized formula could be predicted by decision rules. It would be very significant to optimize the compatibility of categorized formula and guide the clinical-practice.
Drug Interactions ; Drug Prescriptions ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Medicine, Chinese Traditional ; methods ; Models, Theoretical

Prediction on pharmacodynamic action of categorized formulas is presented with the theory of support vector regression (SVR) in this paper. A prediction model of pharmacodynamic action of categorized formulas based on SVR was set up in order to predict the law of the compatibility of the categorized formulas. Pharmacodynamic action of various categorized formulas could be predicted based on this model. It is very significient to optimize the compatibility of categorized formulas and clinical practice. This model was applied to the research of the law of compatibility in three categorized formulas for tonifying kidney yang which contains shenqi pill, yougui pill and yougui drink. As indicated in the model prediction, pharmacodynamic actions of several compatibilities of the categorized formulas are superior to that of the three original formulas for tonifying kidney yang.
Algorithms ; Drug Synergism ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; administration & dosage ; Models, Theoretical ; Support Vector Machine

Objective To investigate the correlation of single nucleotide polymorphisms( SNP) of rs228648 and rs2890565 in urotensin Ⅱ (UTS2)gene with polycystic ovary syndrome(PCOS). Methods The genotypes of two SNPs in UTS2 gene were determined through polymerase chain reaction Tin-shift genotyping method. 101 Chinese Han families trios in Shandong Province consisting of fathers,mothers,and affected daughters with PCOS and 105 healthy women were recruited. The physiological and biochemical parameters including serum follicular stimulating hormone(FSH),luteinizing hormone( LH),testosterone,fasting plasma glucose,and insulin were also measured. Results The distributions of three genotypes and two alleles of SNP rs228648 in UTS2 gene were similar between PCOS group and control group. The distributions of genotypes of SNP rs2890565 in UTS2 gene differed significantly between PCOS group and control group (P<0. 05). The frequency of A allele of SNP rs2890565 in UTS2 gene was significantly higher in PCOS group than that in control group( P<0.05). Transmission disequilibrium test(TDT) did not show significantly biased transmission of two different alleles from parents to affected daughters at rs228648 locus (P>0. 05) ,but showed an excess transmission of A allele from heterozygous parents to affected offspring at rs2890565 locus (P<0. 05). The carriers with GG genotype of SNP rs228648 had significantly higher HOMA-IR compared to those with AA and AG genotypes. The carriers with AA or AG genotype of SNP rs2890565 had significantly higher fasting plasma glucose and fasting insulin compared to those with GG genotypes. HOMA-IR in cases with AA genotype was significantly higher than that with GG genotype. Conclusions There is no association of SNP rs228648 with PCOS, but exists association with insulin resistance. The genetic polymorphism of UTS2 gene rs2890565 may be associated with PCOS,and the higher frequency of A allele is likely to contribute to PCOS.

In order to explore the influence of psychological stress on the reproductive axis, we started with the original data of biology from animal experiments, then we conducted the factor analysis of 6 important bio-regulatory factors and established the Factor Analysis Model for the endocrine network of reproduction axis under psychological stress. Based on the biological data obtained from animal experiments, it is found that, compared with the relationship seen in the factor analysis model in normal condition, the relationship among the biological factors is more complicated. The key factor, GnRH, has lost its strong regulating action on the subordinate factors, especially on E2; on the other hand, beta-EP has very strong regulating action on E2, and E2 is controlled mainly by beta-EP.
Animals ; Estradiol ; blood ; physiology ; Female ; Follicle Stimulating Hormone ; blood ; physiology ; Gonadotropin-Releasing Hormone ; blood ; physiology ; Models, Biological ; Neurosecretory Systems ; physiology ; Rats ; Reproduction ; physiology ; Stress, Psychological ; metabolism ; physiopathology ; beta-Endorphin ; blood ; physiology