BACKGROUNDMultiple epiphysis dysplasia (MED) is a common skeletal dysplasia with a significant locus heterogeneity. In the majority of clinically defined cases, mutations have been identified in the gene encoding cartilage algometric matrix protein (COMP).

METHODSFive patients were included in the study. Linkage analysis and mutation analysis of the COMP gene were conducted in the patients and their family members.

RESULTSWe have identified a novel mutation in axon 14 of COMP gene in the family.

CONCLUSIONSThis mutation produced a severe MED phenotype with marked short stature, early onset osteoarthritis, and remarkable radiographic changes. Our results extended the range of disease-causing mutations in COMP gene and contributed more information about relationship between mutations and phenotype.

Adolescent ; Asian Continental Ancestry Group ; Cartilage Oligomeric Matrix Protein ; genetics ; Female ; Humans ; Male ; Osteochondrodysplasias ; genetics ; Pedigree ; Point Mutation ; genetics

BACKGROUNDCyclosporine A (CsA) has been widely used in the treatment of aplastic anemia (AA), but the application of CsA was limited in patients who had liver diseases or abnormal liver function due to its liver toxicity. Glycyrrhizin has long been used in China in the treatment of various liver diseases to lower transaminases. In this study, we observed the efficacy and safety of glycyrrhizic acid combined with CsA in the treatment of newly diagnosed patients with non-severe AA (NSAA).

METHODSA total number of 76 patients with newly diagnosed NSAA were enrolled into the study at our hospital between July 2005 and June 2010. The patients were divided randomly into two groups: the glycyrrhizin-treatment group (group A) and the control group (group B) with 38 patients in each group. All patients received 3 - 5 mg×kg(-1)×d(-1) CsA for at least 4 months and were treated either with or without glycyrrhizin for 4 months.

RESULTSsixty-eight patients were eligible for evaluation. In the control group, 9.09% patients (n = 3) achieved a complete response while 51.52% (n = 17) attained a partial response. The overall response rate was 60.61% (n = 20). The remaining 13 patients (39.39%) did not have any response. In the glycyrrhizin-treatment group, complete response rate was 20% (n = 7) and partial response rate was 62.86% (n = 22). The overall response rate was 82.86% (n = 29) and the non-response rate was 17.14% (n = 6). Response rate was significantly increased with the addition of glycyrrhizin to CsA compared with CsA alone (P < 0.05).

CONCLUSIONThe combination of glycyrrhizin and cyclosporine regimen was an effective treatment for NSAA in terms of improvement of response rate, reduction in CsA-related liver injury, and attenuation of severity of nausea and other adverse events in the treatment of patients with NSAA.

Adolescent ; Adult ; Aged ; Anemia, Aplastic ; drug therapy ; immunology ; Cyclosporine ; administration & dosage ; adverse effects ; Drug Therapy, Combination ; Female ; Glycyrrhizic Acid ; administration & dosage ; adverse effects ; Humans ; Interferon-gamma ; blood ; Interleukin-2 ; blood ; Male ; Middle Aged

Hematopoietic stromal cells, being the essential ingredient of the hematopoietic microenvironment, play very important roles in the control and regulation of self-renewal, proliferation and differentiation of hematopoietic stem cells (HSC) via complex interactions of cell-cell, cell-humoral and cell-extracellular matrix. Evidence from in vivo experiment has proved that HSC derived from normal mice could reconstitute hematopoiesis of mice with HSC defects but failed to reconstitute hematopoiesis of those mice with microenvironment defects, showing the importance of hematopoietic microenvironment in the maintenance of hematopoiesis in vivo. A well-known long-term culture (LTC) system established by Dexter demonstrated in another way that stromal cell layer in the system could support ex vivo hematopoiesis for several months, even more than one year under the optimal conditions. It, however, has not been demonstrated that what is the key elements and in which way the ex vivo hematopoiesis could be maintained for so long time. As the inventions for the large-scale screening methodologies the suppression subtractive hybridization (SSH) was chosen for the screening differentially expressed genes expressed by LTC cultured stromal cells but not by the uncultured bone marrow cells (BMC). mRNA extracted from both cultured adherent cells (tester) and BMC (driver) were hybridized according to the protocol provided by CLONTECH. Total of 130 clones differentially expressed by cultured cells were randomly picked up and 106 ESTs were obtained after sequencing. They represent 26 identical or similar genes and 7 novel genes after the bioinformatics analysis. 5 of the novel genes with the entire open reading frame, without functional clues, have been cloned into the mammalian expression vectors and the functions of them in the control of proliferation and differentiation of HSC will be further exploring. The most interesting discovery is that 3 novel genes have signal peptides, implying the potential discovery of novel growth factors as 80% known growth factors have signal peptides. Our experimental results suggest that: (a) based on the results of subtractive efficiency, the SSH could be a reliable method to screen differentially expressed genes; (b) gene expression may be regulated by multiple factors, even conditioning-dependent, in this experiment the genes expressed by bone marrow stromal cells are LTC-cultivation inducible; (c) it is possible to find interesting genes or special gene after relatively large-scale screen.
Animals ; Cells, Cultured ; DNA, Complementary ; genetics ; metabolism ; Deoxyribonucleases, Type II Site-Specific ; metabolism ; Expressed Sequence Tags ; Female ; Gene Expression Profiling ; Hematopoietic Stem Cells ; cytology ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Polymerase Chain Reaction ; RNA, Messenger ; genetics ; metabolism ; Stromal Cells ; cytology ; metabolism

The SARS epidemic is breaking out worldwide. To select suitable herbal drugs for clinical uses is important and urgent amongst the controversial treatment proposals. Nine pharmacological experimental models were used to evaluate the comprehensive efficacy of traditional Chinese remedies by cross validation in different institutes. Eight drugs were optimized for controlling different symptoms of SARS.
Animals ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; isolation & purification ; therapeutic use ; Humans ; Multiple Organ Failure ; prevention & control ; Phytotherapy ; Plants, Medicinal ; chemistry ; Severe Acute Respiratory Syndrome ; drug therapy

BACKGROUNDPseudoachondroplasia (PSACH) is an autosomal-dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein (COMP). Clinical diagnosis of PSACH is based primarily on family history, physical examination, and radiographic evaluation. There is evidence that decreased serum COMP concentration may serve as a diagnostic marker in PSACH. Here, we investigated the role of this gene and the serum COMP concentration in Chinese patients with PSACH.

METHODSA family with three patients and a sporadic case were recruited. Genomic and phenotypic data were recorded. The diagnosis of PSACH was made on the base of clinical evaluation. The genomic DNA was extracted from peripheral blood leukocytes. The 8-19 exons and flanking intron-exon boundary sequences of COMP were amplified by polymerase chain reaction (PCR) and screened for mutation by direct DNA sequencing. Serum COMP concentrations of 4 patients and age-compatible control group of 20 unrelated healthy subjects were analyzed on the basis of an ELISA Kit for human cartilage oligomeric matrix protein.

RESULTSA deletion (c.1447-1455del) was identified in exon 13 in the sporadic case. The mean serum COMP concentrations of four patients (3.12+/-2.28) were significantly lower than those of control group (10.86+/-2.21, P<0.05). There was no overlap in the distribution of serum COMP concentration between PSACH patients and controls.

CONCLUSIONSMutations in COMP gene are responsible for the PSACH. Serum COMP concentration may be suggested as an additional diagnostic marker to aid clinical findings in suspected cases of PSACH.

Cartilage Oligomeric Matrix Protein ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Exons ; genetics ; Extracellular Matrix Proteins ; blood ; genetics ; Female ; Glycoproteins ; blood ; genetics ; Humans ; Male ; Matrilin Proteins ; Mutation ; Osteochondrodysplasias ; blood ; genetics ; Pedigree ; Polymerase Chain Reaction

OBJECTIVETo compare the efficacy and safety of BD regimen combined with cyclophosphamide(CTX) and pirarubicin chemotherapy(P-CAD) for patients with relapse/refractory multiple myeloma(MM).

METHODSTwenty-eight cases of relapse/refractory MM were enrolled in a group of P-CAD regimen, 36 cases of relapse/retractory MM treated with BD were used as controls. The therapeutic efficacy and adverse reactions of 2 regimens for patients with relapse/retractory MM were compared and analyzed.

RESULTSThe overall response rate (CR+NCR+PR+MR) of the 28 cases treated with P-CAD regimen was 85.7%, and the response rate (CR+PR) was 75.0%. The median progression-free survival time were 16.1 months, and the average survival time were 30.6 months, while the overall response rate of the 36 patients treated with BD regimen was 63.9%, and the response rate was 55.6%. The median progression-free survival time were 13.7 months, and the average survival time were 26.7 months. The adverse reactions of 2 groups included gastrointestinal reactions, peripheral neuropathy, fatigue, skin rashes, leucopenia and thrombocytopenia, and they were all well tolerated.

CONCLUSIONBD regimen combined with cyclophosphamide and pirarubicin chemotherapy can improve the response rate of patients with relapse/refractory multiple myeloma, and shows the trend of prolonging PFS and survival times. Patients were well tolerated, and this regimen is a new choice in treatment of relapse/refractory MM.

Objective::To explore the clinical efficacy of modified Sanzi Yangqintang combined with colon hydrotherapy in the treatment of non-alcoholic fatty liver disease (NAFLD) with phlegm-dampness. Method::Totally 100 patients with NAFLD were selected and randomly divided into treatment group (50 cases) and control group (50 cases). Both groups were orally given silybin and glycyrrhizic acid diamine capsules.The treatment group was also added with modified Sanzi Yangqintang and colon hydrotherapy.The treatment lasted for 7 days.The control group was also added with saline colon hydrotherapy.Main traditional Chinese medicine (TCM) syndrome scores and liver function indexes before and after treatment [alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamate transpeptidase (GGT)], blood lipid routine [cholesterol (TCH), triglyceride (TG)], inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], FibroScan measurement [liver stiffness measurement (LSM), controlled attenuation parameters (CAP)], uric acid and body weight changes were observed.Adverse reactions were observed, and the patient's medication safety was evaluated. Result::TCM syndrome score, liver enzyme index, blood lipid index, inflammatory factor index, FibroScan CAP, uric acid and body weight of the two groups were significantly reduced than those before treatment(P<0.05, P<0.01) .There was no significant difference in liver enzymes, TCH, IL-6 and LSM between treatment group and control group.And TCM syndrome scores, UA, TNF-α, FibroScan CAP decreased were significantly different from control group (P<0.05). Conclusion::Modified Sanzi Yangqintang combined with colon hydrotherapy can not only alleviate NAFLD with phlegm-dampness symptoms, but also significantly reduce triglyceride, tumor necrosis factor and FibroScan CAP and body mass, with certain clinical efficacy in a short term.