Further understanding on osteopetrotic femoral fractures: a case report and literature review.

BACKGROUND: Osteopetrosis is a genetic disease characterized by defects in osteoclast formation and function. There were a few cases of subtrochanteric femur fractures treated with dynamic hip screw (DHS) in patients with osteopetrosis, but unfortunately the healing outcome was rather poor. CASE PRESENTATION: We present our experience for treating a patient with intermediate autosomal recessive osteopetrosis (IRO) suffering from subtrochanteric femur fracture. In this case, we successfully used dynamic hip screw (DHS) internal fixation through meticulous preoperative planning and postoperative care, as well as application of surgical techniques. The patient displayed stable internal fixation with no limitation of activities during follow-up for 15 months. In addition to this case, a review of previous case reports showed an increasing number of case reports demonstrating that surgical treatment-related complications could be avoided preoperatively, intraoperatively, and postoperatively. CONCLUSION: DHS for this patient, who suffered from subtrochanteric fractures with osteopetrosis, was successfully implemented. In the light of a comprehensive literature review, preoperative planning, surgical techniques, and postoperative rehabilitation care can significantly reduce the complications.

MicroRNA-145 Suppresses Osteosarcoma Metastasis via Targeting MMP16.

BACKGROUND: Metastasis is a leading cause of mortality for osteosarcoma (OS) patients, and its molecular pathological mechanisms remain to be elucidated. Previous studies have suggested a significant role of microRNAs (miRNAs) in the control of cancel cell migration and invasion. METHODS: Real-time PCR was used to screen the differentially expressed miRNAs between OS with or without metastasis, and miR-145 underexpression was observed in metastatic OS. Luciferase assay was performed to validate the target gene. RESULTS: Further, we identified three genes, MMP16, ADAM17 and metadherin, as possible targets of miR-145. We identified MMP16 as a target gene of miR-145 and ruled out ADAM17 and metadherin as targets in OS using a dual luciferase reporter system. Subsequently, we determined and compared the expression level of MMP16 in human OS samples and showed that the mRNA and protein levels of MMP16 were significantly up-regulated in primary OS with metastasis compared with those without metastasis. We also altered miR-145 expression by transfecting OS cells with miR-145 mimics or inhibitors. MMP16 expression was similarly downregulated in the cells transfected with miR-145 mimics or MMP16-specific siRNA, and the invasive and migratory capability of those cells was significantly suppressed compared with negative controls. MMP16 expression was consistently significantly upregulated in the cells transfected with miR-145 inhibitors, and the invasive and migratory capability of those cells was significantly promoted compared with negative controls. Conclcusion: Our results suggest that miR-145 functions as a tumor metastasis suppressor gene by down-regulating MMP16 and may be a potential target in osteosarcoma treatment.

Association study of susceptibility loci with specific breast cancer subtypes in Chinese women.

To determine whether recent genome-wide association studies that reported 45 susceptibility loci in European women are also risk factors for breast cancer in Chinese women. We selected and genotyped 40 single nucleotide polymorphisms (SNPs) using the Sequenom iPlex platform in a female Chinese cohort of 2,901 breast cancer cases and 2,789 healthy controls. We evaluated these SNPs with the risk of breast cancer and further by estrogen receptor (ER) status, progestin (PR) status, human epidermal growth factor receptor-2 (HER-2) status, and four breast cancer subtypes (Luminal A type, Luminal B type, HER-2 overexpression type and Basal-like type). We first confirmed that the SNP rs9693444 on 8p12 was associated with breast cancer in Chinese women (P = 6.44 × 10(-4)). Furthermore, we identified four susceptibility loci that were associated with specific tumor subtypes. Statistically significant differences were detected with the association of rs6828523 (4q34.1/ADAM29) with ER-positive breast cancer (P = 1.27 × 10(-3)) and the association of rs4849887 (2q14.2) with PR-positive breast cancer (P = 1.29 × 10(-3)). Of the four breast cancer subtypes, the associations of rs12493607 (3p24.1/TGFBR2) with HER-2 overexpression in breast cancer (P = 1.09 × 10(-3)) and rs11075995 (16q12.2/FTO) with basal-like breast cancer (P = 1.64 × 10(-4)) were statistically significant. This study is the first to show that these 5 susceptibility loci (8p12, 4q34.1/ADAM29, 2q14.2, 3p24.1/TGFBR2, and 16q12.2/FTO) correlate with breast cancer (overall and specific subtypes) in Chinese women, which has improved our understanding of the genetic basis of specific breast cancer subtypes.

Induction of 9-cis-epoxycarotenoid dioxygenase in Arabidopsis thaliana seeds enhances seed dormancy.

Full understanding of mechanisms that control seed dormancy and germination remains elusive. Whereas it has been proposed that translational control plays a predominant role in germination, other studies suggest the importance of specific gene expression patterns in imbibed seeds. Transgenic plants were developed to permit conditional expression of a gene encoding 9-cis-epoxycarotenoid dioxygenase 6 (NCED6), a rate-limiting enzyme in abscisic acid (ABA) biosynthesis, using the ecdysone receptor-based plant gene switch system and the ligand methoxyfenozide. Induction of NCED6 during imbibition increased ABA levels more than 20-fold and was sufficient to prevent seed germination. Germination suppression was prevented by fluridone, an inhibitor of ABA biosynthesis. In another study, induction of the NCED6 gene in transgenic seeds of nondormant mutants tt3 and tt4 reestablished seed dormancy. Furthermore, inducing expression of NCED6 during seed development suppressed vivipary, precocious germination of developing seeds. These results indicate that expression of a hormone metabolism gene in seeds can be a sole determinant of dormancy. This study opens the possibility of developing a robust technology to suppress or promote seed germination through engineering pathways of hormone metabolism.

Optimal intensity shock wave promotes the adhesion and migration of rat osteoblasts via integrin ß1-mediated expression of phosphorylated focal adhesion kinase.

To search for factors promoting bone fracture repair, we investigated the effects of extracorporeal shock wave (ESW) on the adhesion, spreading, and migration of osteoblasts and its specific underlying cellular mechanisms. After a single period of stimulation by 10 kV (500 impulses) of shock wave (SW), the adhesion rate was increased as compared with the vehicle control. The data from both wound healing and transwell tests confirmed an acceleration in the migration of osteoblasts by SW treatment. RT-PCR, flow cytometry, and Western blotting showed that SW rapidly increased the surface expression of α5 and ß1 subunit integrins, indicating that integrin ß1 acted as an early signal for ESW-induced osteoblast adhesion and migration. It has also been found that a significant elevation occurred in the expression of phosphorylated ß-catenin and focal adhesion kinase (FAK) at the site of tyrosine 397 in response to SW stimulation after the increasing expression of the integrin ß1 molecule. When siRNAs of integrin α5 and ß1 subunit were added, the level of FAK phosphorylation elevated by SW declined. Interestingly, the adhesion and migration of osteoblasts were decreased when these siRNA reagents as well as the ERK1/2 signaling pathway inhibitors, U0126 and PD98059, were present. Further studies demonstrated that U0126 could inhibit the downstream integrin-dependent signaling pathways, such as the FAK signaling pathway, whereas it had no influence on the synthesis of integrin ß1 molecule. In conclusion, these data suggest that ESW promotes the adhesion and migration of osteoblasts via integrin ß1-mediated expression of phosphorylated FAK at the Tyr-397 site; in addition, ERK1/2 are also important for osteoblast adhesion, spreading, migration, and integrin expression.

Chemotherapy-induced prospective memory impairment in patients with breast cancer.

OBJECTIVE: This study aimed to investigate the event-based prospective memory (EBPM) and time-based prospective memory (TBPM) in chemotherapy-induced cognitive impairment in patients with breast cancer. METHODS: Forty patients with breast cancer who underwent adjuvant chemotherapy and 40 age-matched and education-matched healthy women were administered with a battery of neuropsychological tests including EBPM and TBPM tasks. RESULTS: A significant difference between breast cancer patients and controls was found in the scores on the mini-mental state examination (t = -11.684, p < 0.01), verbal fluency test (t = -7.939, p < 0.01), and digit span (t = -2.538, p < 0.05). Compared with healthy controls, breast cancer patients exhibited a poorer performance on EBPM (t = -7.096, p < 0.01) but not on TBPM (t = -1.921, p > 0.05). CONCLUSIONS: Our results suggest that breast cancer patients who had undergone adjuvant chemotherapy show deficits in EBPM but not in TBPM.

Impact of dyslipidemia on the severity of symptomatic lumbar spine degeneration: A retrospective clinical study.

Background: Lumbar intervertebral disc degeneration (IVDD) is an important cause of low back pain or sciatica, and metabolic factors play an important role. However, little is known about the relationship of dyslipidemia to the risk of intervertebral disc degeneration (IVDD). This study aimed to assess the impact of serum lipid levels on the severity of lumbar disc degeneration and to investigate its association with endplate inflammation. Methods: We conducted a case retrospective study in which a total of 302 hospitalized Chinese patients were recruited, of whom 188 (112 males and 76 females; mean age: 51.66 years) were without underlying disease, while the remaining 114 patients (51 males and 63 females; mean age: 62.75 years) had underlying diseases. We examined fasting serum lipid levels for total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Magnetic resonance imaging (MRI) was used to determine endplate inflammation. Pfirrmann grading and Weishaupt grading were used to evaluate the severity of intervertebral disc degeneration and facet joint degeneration, respectively. Results: There was no difference in age, gender, and general BMI between the two groups (P > 0.05), but there were significantly high levels in TC, LDL-C, and LDL-C/HDL-C (P = 0.04, P = 0.013, P = 0.01, respectively). TG and HDL-C showed no significant difference (P = 0.064, P = 0.336, respectively). The multivariate logistic regression model showed that age was a risk factor for the occurrence of endplate inflammation. In the group without underlying diseases, age, but not other indicators, was a risk factor for the occurrence of endplate inflammation (P < 0.01), In the group with underlying diseases, none of the patient indicators was directly related to the occurrence of endplate inflammation (P > 0.05). A nonlinear machine learning model was used to measure the contribution of each factor to the disease outcome and to analyze the effect between the top three contributing factors and the outcome variables. In patients without underlying diseases, the top three factors contributing to the severity grading of intervertebral disc degeneration were age (32.9%), high-density lipoproteins (20.7%), and triglycerides (11.8%). For the severity grading of facet joint degeneration, the top three contributing factors were age (27.7%), high-density lipoproteins (19.4%), and triglycerides (14.6%). For patients with underlying diseases, the top three factors contributing to intervertebral disc degeneration were age (25.4%), BMI (15.3%), and low-density lipoprotein/high-density lipoprotein ratio (13.9%). In terms of degree classification for facet joint degeneration, the top three contributing factors were age (17.5%), BMI (17.2%), and total cholesterol (16.7%). Conclusion: This study shows that age, high-density lipoprotein, and triglycerides affect the degree of degeneration in patients with symptomatic lumbar degeneration without underlying diseases. Age and BMI are two major factors affecting the severity of degeneration in patients with underlying diseases, and dyslipidemia is a secondary factor. However, there is no clear association between dyslipidemia and the occurrence of endplate inflammation in either group.

Stromal cell-derived factor-1 may play pivotal role in distraction-stimulated neovascularization of diabetic foot ulcer.

Diabetic foot ulcer (DFU) has become a major medical, social and economic concern worldwide. It is highly desirable to develop promising new solutions to effectively and appropriately treat DFU. In recent years, investigators have used an innovative technology called proximal tibial cortex transverse distraction (PTCTD) to treat DFU and have achieved satisfactory results in terms of improved wound healing and circumvention of amputation as a consequence of enhanced neovascularization and perfusion of the ulcerated feet after the operation, but the underlying mechanism has not been explored. Previous studies have suggested that in addition to stimulating osteogenesis, bone distraction also facilitates neovascularization, which may be associated with the chemokine stromal cell-derived factor-1 (SDF-1). As an important member of the chemokine family, SDF-1 is primarily responsible for the homing and migration of endothelial progenitor cells (EPCs) or bone marrow-derived mesenchymal stem cells (BMSCs), and plays a central role in the process of neovascularization. In vivo or in vitro experiments show that bone distraction can induce the expression of SDF-1 and increase its plasma concentration. Moreover, some researchers have found that an insufficient level of SDF-1 in the circulation and wounds of patients with DFU can lead to impaired neovascularization. Therefore, we believe that SDF-1 plays an important role in promoting neovascularization of DFU as a result of bone distraction. We summarize the currently relevant literature to put forward an undisclosed but meaningful mechanism of bone distraction in the treatment of DFU.

Radiolysis of carbamazepine by electron beam: Roles of transient reactive species and biotoxicity of final reaction solutions on rotifer Philodina sp.

Electron beam (EB) has proven to be an effective advanced oxidation reduction process (AORP) to degrade the psychiatric drug carbamazepine (CBZ); however, the degradation mechanism and the toxicity of the final reaction solutions to aquatic microorganisms needed further investigation. In this study, CBZ was eventually degraded and even mineralized by EB treatment, where the degradation of CBZ followed the pseudo-first-order kinetics with R2 > 0.98. Acidic conditions, presence of an additional oxidant (2.5 mmol L-1 H2O2), and O2/air-saturated conditions improved the degradation efficiency of CBZ, as well as the radiation chemical yield (G-value defined as the efficiency of the irradiation process). Concentrations of transient reactive species (TRS) caused by EB were quantified under different conditions at doses of 0.956 and 3.17 kGy, and the apparent quantum yield of CBZ degradation was in the order of OH > H > eaq-. However, the contribution of these species to CBZ degradation was in the order of OH > eaq- >H due to the generation of only a small amount of H. Findings regarding the changes of in CBZ degradation intermediates, short-chain fatty acids (SCFAs), and total organic carbon showed that CBZ can gradually be mineralized into CO2/CO32-, H2O, and NH3/NH4+ by the EB process. Additionally, an excellent rotifer survival rate after 5-day culturing in the reaction solutions resulting from 5-kGy treatment indicated that EB can be a safe AORP to mineralize CBZ in solution. These findings provide scientific proof for the EB being an effective AORP for removal of psychiatric drugs from aqueous solutions, laying the foundation for future remediation research.

The efficacy and safety of denosumab in postmenopausal women with osteoporosis previously treated with bisphosphonates: A review.

OBJECTIVE: The objective of this study was to assess the efficacy and safety of denosumab therapy in osteoporotic postmenopausal women who were previously treated with bisphosphonates. METHODS: Meta-analyses of four available randomised controlled trials that compared osteoporotic patients who switched to denosumab from bisphosphonates (n â€‹= â€‹1416) and those who continued bisphosphonates therapy (n â€‹= â€‹1411) were included. RESULTS: The increase in bone mineral density (BMD) of both the spine and hip was significantly higher in patients who shifted to denosumab than in those who continued bisphosphonates. Despite the incidence of adverse events (AEs) and fractures being comparable, treatment withdrawal owing to AEs was significantly less frequent in the denosumab group. CONCLUSION: The outcomes and treatment compliance were improved in postmenopausal osteoporotic women who shifted to denosumab from bisphosphonates. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The replacement of bisphosphonates with denosumab may lead to better therapeutic efficacy and fewer adherence barriers â€‹than those with continued usage of bisphosphonates, which in the future may guide the choice of drug therapy in clinics.