Chromosome 1q21 gains confer inferior outcomes in multiple myeloma treated with bortezomib but copy number variation and percentage of plasma cells involved have no additional prognostic value.

Chromosome 1q21 aberrations have not been yet been made part of routine clinical tests and their effect in multiple myeloma is still under investigation. The prognostic value of copy number variation and percentage of plasma cells involved have remained unclear. In the present study, we analyzed the prognostic value of 1q21 in a series of 290 cases of newly diagnosed multiple myeloma treated in a prospective, non-randomized clinical trial (BDH 2008/02). We found that incidence of 1q21 aberration increased at relapse, but its copy numbers and proportion of cells involved did not change. Gains of 1q21 had no impact on survival in patients receiving thalidomide-based treatment but conferred a significantly inferior prognosis in patients under bortezomib-based chemotherapy and was an independent adverse prognostic factor for progression free survival (HR 3.831; 95%CI: 2.125-6.907; P<0.001) and overall survival (HR 3.245; 95%CI: 1.555-6.773; P=0.002). Strikingly, our results showed that the copy number variation and clone size harboring 1q21 gains carried no additional prognostic value and patients with 1q21 gains did not benefit significantly from regimens incorporating bortezomib. Our results indicate that three copies of 1q21 and 20% of plasma cells with this abnormality were enough to confer bortezomib resistance. Therefore, chromosome 1q21 gains should be considered a high-risk feature in multiple myeloma receiving bortezomib therapy.

[Anatomical characteristics of the pelvic floor muscles in young nulliparous women based on three-dimensional MRI].

OBJECTIVE: To analyse anatomical characteristics of the pelvic floor in young nulliparous volunteers based on three-dimensional MRI. METHODS: Thin-slice MRI was performed in 25 young nulliparous volunteers in Southern Medical University, MRI were imported into Mimics 10.01 for 3D reconstruction.Using 3D models we measured follow indicators: the levator ani muscle volume (LVOL) , levator plate angle (LPA), levator hiatus width (LH-W)and length (LH-L), distance between symphysis and levator sling muscle (LSG). RESULTS: (1) 25 cases of pelvic three-dimensional models was successfully constructed, including the pelvis, pelvic organs and the pelvic floor muscles (including the ischial coccyx muscle, levator ani muscle and its various components, perineal muscles), the models could be able to clearly reflect the level of the pelvic floor muscles; (2) 25 cases of levator ani muscle measurement results:LVOL: (34 ± 6) cm(3), LPA: (43 ± 4) °, LH-W: (33 ± 4) mm, LH-L: (54 ± 5) mm, left LSG: (18.8 ± 2.5) mm, right LSG: (18.3 ± 2.5) mm. CONCLUSIONS: It is an effective way to use the computer to reconstruct the 3D model of female pelvic floor muscles using MRI data set. The quantitative analysis of levator ani muscle three-dimensional model can be assessed pelvic floor function, which is of great value in clinical practice.It is helpful to understand the pelvic floor disorders pathogenesis, clinical diagnosis, treatment options and treatment evaluation to provide reference standards.

The influence of the closing and opening muscle groups of jaw condyle biomechanics after mandible bilateral sagittal split ramus osteotomy.

OBJECTIVE: To investigate the influence of the closing and opening muscle groups of the jaw on mandibular stability after mandibular bilateral sagittal split ramus osteotomy (BSSRO). MATERIALS AND METHODS: To establish finite element models of four conditions (the normal mandible, preoperative mandibular prognathism, postoperative (BSSRO) mandibular prognathism, and mandibular prognathism following virtual BSSRO), we imported Digital Imaging and Communications in Medicine (DICOM) data into three-dimensional reconstruction software. Finite element analysis software and statistical software were used for analysis of the condylar stress distribution as a function of condylar position during the actions of jaw closing and jaw opening muscle groups. RESULTS: The stress distribution of the normal mandibular bilateral condyle was statistically different from the normal mandibular condyle, indicating that bilateral structures are asymmetrical. There was a significant difference in stress distributions with condyle position between healthy control patients and patients prior to mandibular prognathism surgery (P<0.05). There was no significant difference in stress distributions between the normal mandible and the mandible following virtual surgery or real mandibular prognathism surgery. Additionally, there was no significant difference at 6 months after mandibular prognathism surgery (P>0.05). CONCLUSIONS: Bilateral structures of the normal mandible were asymmetrical. After mandibular bilateral sagittal split ramus osteotomy, variation of the force arms of closing and opening muscle groups of the jaw was one of the major factors influencing mandibular stability. Virtual surgery is a promising strategy for preoperative planning to improve surgical success and reduce complications.

Effect of tetrandrine on the TGF-ß-induced smad signal transduction pathway in human hypertrophic scar fibroblasts in vitro.

PURPOSE: To evaluate in vitro effects of tetrandrine on the TGF-ß-induced smad signal transduction pathway and cellular function altered by tetrandrine in human hypertrophic scar fibroblasts (HSFs). METHODS: HSFs were exposed to four different treatments (control, tetrandrine, TGF-ß(1) and mixture). After 48 h culture, expression of TGF-ß1, Smad2 and Smad7 were examined using reverse transcription PCR and Western blotting. To evaluate cellular function alteration, morphological changes of HSFs were observed under an inverted microscope, expression of type I and III collagen were tested by immunocytochemistry, and cell cycles were analyzed by flow cytometry. RESULTS: Expression of Smad7 increased while expression of Smad2 and TGF-ß1 mRNA decreased in HSFs with tetrandrine. In addition, type I and III collagen was suppressed and S phase of the cell cycle markedly shortened in HSFs by tetrandrine. CONCLUSIONS: These results suggest that tetrandrine inhibits HSFs at least partially through induction of Smad7 and decrement of Smad2 resulting in inhibition of TGF-ß1 transcription and its intracellular signaling, which led to reduction of type I and III collagen production and suppression of cell reproductive activity.