A Comparison Between Fondaparinux Sodium and Low-Molecular-Weight Heparin in Preventing Patients Undergoing Hip Replacement from Deep Vein Thrombosis.

OBJECTIVES: Total hip arthroplasty (THA) is a highly successful and effective surgery for improving hip functions and relieving pain. However, the lower extremities are prone to deep vein thrombosis (DVT) and swelling after surgery, thereby delaying recovery. In this study, we investigated the preventive effects of fondaparinux sodium (FS) and low-molecular-weight heparin (LMWH) on DVT of the lower extremity after THA. METHODS: Firstly, 60 patients who underwent THA at the First Affiliated Hospital of Wannan Medical College from March 2020 to December 2020 were included. Next, the patients were randomly divided into an LMWH group (n = 30) and an FS group (n = 30). Then, the indexes related to DVT were compared between both groups. RESULTS: Specifically, the differences in baseline data, such as age, gender and body mass index (BMI), between the two groups were not statistically significant. The postoperative weight bearing time of patients in the FS group was much shorter than that in the LMWH group. CONCLUSION: Subcutaneous injection of FS not only exhibits superior effects to LMWH in preventing DVT after THA but also has a correlation with reducing the risk of thrombosis and improving patient symptoms.

Prognostic analysis and nomogram establishment in patients with head and neck myoepithelial carcinoma.

PURPOSE: To further explore the clinicopathological characteristics and determinants of survival of patients with HNMC. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was used to collect the data of patients diagnosed with HNMC from 1975 to 2016. Kaplan-Meier analysis and log-rank testing compared the survival difference. Cox hazard regression models analyzed the survival outcome and prognostic factors. Concordance index (C-index) verified the nomogram. RESULTS: A total of 322 eligible cases were retrieved. The mean age at diagnosis was 61 years old and the male to female ratio was 1:1. The major salivary gland was the most common primary site (72.5%). Patients with adjuvant radiation showed better overall survival (OS) (P < 0.05). Advanced grade, N, M stage and nonsurgery contributed independently to shorter OS, while the advanced N, M stage and nonsurgery contributed independently to shorter disease-specific survival (DSS) (P < 0.05). The C-index of OS-specific nomogram was 0.768 (95% CI 0.726-0.810). CONCLUSIONS: HNMC usually appears in elderly patients and has no gender difference. The 5-year OS and DSS rates are 70% and 79.8%, respectively. Grade, N, M stage and surgery are independent prognostic factors for OS, while N, M stage and surgery are independent prognostic factors for DSS. Compared with the surgery alone, adjuvant radiation appears to offer a significant OS benefit for patients with stage III or IV.

Instance Sequence Queries for Video Instance Segmentation with Transformers.

Existing methods for video instance segmentation (VIS) mostly rely on two strategies: (1) building a sophisticated post-processing to associate frame level segmentation results and (2) modeling a video clip as a 3D spatial-temporal volume with a limit of resolution and length due to memory constraints. In this work, we propose a frame-to-frame method built upon transformers. We use a set of queries, called instance sequence queries (ISQs), to drive the transformer decoder and produce results at each frame. Each query represents one instance in a video clip. By extending the bipartite matching loss to two frames, our training procedure enables the decoder to adjust the ISQs during inference. The consistency of instances is preserved by the corresponding order between query slots and network outputs. As a result, there is no need for complex data association. On TITAN Xp GPU, our method achieves a competitive 34.4% mAP at 33.5 FPS with ResNet-50 and 35.5% mAP at 26.6 FPS with ResNet-101 on the Youtube-VIS dataset.

A piperidinol-containing molecule is active against Mycobacterium tuberculosis by inhibiting the mycolic acid flippase activity of MmpL3.

Mycobacterium tuberculosis, the causative agent of tuberculosis, remains a major human pathogen, and current treatment options to combat this disease are under threat because of the emergence of multidrug-resistant and extensively drug-resistant tuberculosis. High-throughput whole-cell screening of an extensive compound library has recently identified a piperidinol-containing molecule, PIPD1, as a potent lead compound against M. tuberculosis Herein, we show that PIPD1 and related analogs exert in vitro bactericidal activity against the M. tuberculosis strain mc26230 and also against a panel of multidrug-resistant and extensively drug-resistant clinical isolates of M. tuberculosis, suggesting that PIPD1's mode of action differs from those of most first- and second-line anti-tubercular drugs. Selection and DNA sequencing of PIPD1-resistant mycobacterial mutants revealed the presence of single-nucleotide polymorphisms in mmpL3, encoding an inner membrane-associated mycolic acid flippase in M. tuberculosis Results from functional assays with spheroplasts derived from a M. smegmatis strain lacking the endogenous mmpL3 gene but harboring the M. tuberculosis mmpL3 homolog indicated that PIPD1 inhibits the MmpL3-driven translocation of trehalose monomycolate across the inner membrane without altering the proton motive force. Using a predictive structural model of MmpL3 from M. tuberculosis, docking studies revealed a PIPD1-binding cavity recently found to accommodate different inhibitors in M. smegmatis MmpL3. In conclusion, our findings have uncovered bactericidal activity of a new chemical scaffold. Its anti-tubercular activity is mediated by direct inhibition of the flippase activity of MmpL3 rather than by inhibition of the inner membrane proton motive force, significantly advancing our understanding of MmpL3-targeted inhibition in mycobacteria.

MmpL3 is the flippase for mycolic acids in mycobacteria.

The defining feature of the mycobacterial outer membrane (OM) is the presence of mycolic acids (MAs), which, in part, render the bilayer extremely hydrophobic and impermeable to external insults, including many antibiotics. Although the biosynthetic pathway of MAs is well studied, the mechanism(s) by which these lipids are transported across the cell envelope is(are) much less known. Mycobacterial membrane protein Large 3 (MmpL3), an essential inner membrane (IM) protein, is implicated in MA transport, but its exact function has not been elucidated. It is believed to be the cellular target of several antimycobacterial compounds; however, evidence for direct inhibition of MmpL3 activity is also lacking. Here, we establish that MmpL3 is the MA flippase at the IM of mycobacteria and is the molecular target of BM212, a 1,5-diarylpyrrole compound. We develop assays that selectively access mycolates on the surface of Mycobacterium smegmatis spheroplasts, allowing us to monitor flipping of MAs across the IM. Using these assays, we establish the mechanism of action of BM212 as a potent MmpL3 inhibitor, and use it as a molecular probe to demonstrate the requirement for functional MmpL3 in the transport of MAs across the IM. Finally, we show that BM212 binds MmpL3 directly and inhibits its activity. Our work provides fundamental insights into OM biogenesis and MA transport in mycobacteria. Furthermore, our assays serve as an important platform for accelerating the validation of small molecules that target MmpL3, and their development as future antituberculosis drugs.

Single-dose local administration of parathyroid hormone (1-34, PTH) with ß-tricalcium phosphate/collagen (ß-TCP/COL) enhances bone defect healing in ovariectomized rats.

Parathyroid hormone (1-34, PTH) combined ß-tricalcium phosphate (ß-TCP) achieves stable bone regeneration without cell transplantation in previous studies. Recently, with the development of tissue engineering slow release technology, PTH used locally to promote bone defect healing become possible. This study by virtue of collagen with a combination of drugs and has a slow release properties, and investigated bone regeneration by ß-TCP/collagen (ß-TCP/COL) with the single local administration of PTH. After the creation of a rodent critical-sized femoral metaphyseal bone defect, ß-TCP/COL was prepared by mixing sieved granules of ß-TCP and atelocollagen for medical use, then ß-TCP/COL with dripped PTH solution (1.0 µg) was implanted into the defect of OVX rats until death at 4 and 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, and biomechanics. The results of our study show that single-dose local administration of PTH combined local usage of ß-TCP/COL can increase the healing of defects in OVX rats. Furthermore, treatments with single-dose local administration of PTH and ß-TCP/COL showed a stronger effect on accelerating the local bone formation than ß-TCP/COL used alone. The results from our study demonstrate that combination of single-dose local administration of PTH and ß-TCP/COL had an additive effect on local bone formation in osteoporosis rats.

Prevention of ovariectomy-induced osteoporosis in rats : Comparative study of zoledronic acid, parathyroid hormone (1-34) and strontium ranelate.

Recently, the use of the pharmacological agents strontium ranelate (SR), parathyroid hormone (1-34, PTH) and zoledronic acid (ZA) has come to prominence for the treatment of osteoporosis due to their ability to prevent bone loss in osteoporotic patients. Although much emphasis has been placed on using pharmacological agents for the prevention of disease, much less attention has been placed on which one is more effective. There is still no direct comparative study on these three drugs. The aim of the present study was to investigate the effect of SR, PTH, ZA on preventing ovariectomy-induced osteoporosis in rats. After bilateral ovariectomy the rats randomly received vehicle, SR (500 mg/kg body weight/day, orally), PTH (20 µg/kg/day, subcutaneously) or a single injection of ZA (0.1 mg/kg, i.v.) until death at 12 weeks. The distal femurs were harvested for evaluation of bone metabolism. The rats treated with ZA demonstrated the highest levels of new bone formation as assessed by microcomputed tomography (CT), biomechanical strength, histological analysis and bone metabolism. Furthermore, PTH and SR showed a stronger effect on improving trabecular bone mass at 12 weeks. The results from the present study demonstrate that systemic administration of PTH, SR and ZA could prevent bone loss, while a single dose of ZA has a better effect on preventing ovariectomy-induced osteoporosis than either PTH or SR.

Long intergenic non-protein coding RNA 115 (Linc00115): A notable oncogene in human malignancies.

Long noncoding RNAs (LncRNAs) are RNA transcripts ranging from 200 to 1000 nucleotides that have emerged as critical regulators of gene expression. Growing evidence highlights their involvement in tumor development. In particular, long intergenic non-protein coding RNA115 (Linc00115) has been identified as an oncogene across various human malignancies, with aberrant expression strongly linked to poor clinical outcomes in cancer patients. This review aims to delve into the expression patterns of Linc00115 and elucidate the underlying molecular mechanisms behind its oncogenic properties. Moreover, we discuss the potential utility of Linc00115 as a valuable diagnostic and prognostic biomarker in cancer.

CRISPR/Cas9-mediated silencing of CD44: unveiling the role of hyaluronic acid-mediated interactions in cancer drug resistance.

A comprehensive overview of CD44 (CD44 Molecule (Indian Blood Group)), a cell surface glycoprotein, and its interaction with hyaluronic acid (HA) in drug resistance mechanisms across various types of cancer is provided, where CRISPR/Cas9 gene editing was utilized to silence CD44 expression and examine its impact on cancer cell behavior, migration, invasion, proliferation, and drug sensitivity. The significance of the HA-CD44 axis in tumor microenvironment (TME) delivery and its implications in specific cancer types, the influence of CD44 variants and the KHDRBS3 (KH RNA Binding Domain Containing, Signal Transduction Associated 3) gene on cancer progression and drug resistance, and the potential of targeting HA-mediated pathways using CRISPR/Cas9 gene editing technology to overcome drug resistance in cancer were also highlighted.

Chinese students' perceptions of social networks and their academic engagement in technology-enhanced classrooms.

Using social networks as one of the new instruments of information and communication technologies in recent years has gained popularity. Social networks are used in various political, social, cultural, and educational fields. In education, students increasingly use social networks to create and maintain social relationships and support informal learning methods. The current study investigated the relationship between the use of social networks and academic engagement in Chinese EFL language learners. Using a convenience sampling method, the researcher invited 591 EFL students from Guangdong Province, China to participate in the study. The participants consisted of 307 male learners and 284 female learners, of whom 345 (58.38 %) were B.A., 234 (39.59 %) were M.D. and 2.03 % were Ph.D. To obtain the necessary data, the researcher employed two questionnaires. The researcher distributed the questionnaires that were Social Network Usage Questionnaire and Academic Engagement Questionnaire to the participants. Employing the multivariate regression method and Pearson correlation coefficient in SPSS and Amos, the researcher analyzed the collected data. The results show that there is a significant and positive association between learners' social network usage, their ethnographic factor (age), and their academic engagement. However, other ethnographic factors such as gender and educational level do not affect learners' social networks usage. Also, there is a significant and positive association between the amount of use of social networks for entertainment and components of academic engagement which are cognitive, emotional, and socio-behavioral factors. The use of technology, especially the use of social networks, enhances learners' academic engagement and increases their motivation, energy, and mastering abilities. They provide the ability to easy access for all learners and provide personalized/individual course materials.

Impairment of rigidity sensing caused by mutant TP53 gain of function in osteosarcoma.

Osteosarcoma (OS) is the most common primary malignant pediatric bone tumor and is characterized by high heterogeneity. Studies have revealed a wide range of phenotypic differences among OS cell lines in terms of their in vivo tumorigenicity and in vitro colony-forming abilities. However, the underlying molecular mechanism of these discrepancies remains unclear. The potential role of mechanotransduction in tumorigenicity is of particular interest. To this end, we tested the tumorigenicity and anoikis resistance of OS cell lines both in vitro and in vivo. We utilized a sphere culture model, a soft agar assay, and soft and rigid hydrogel surface culture models to investigate the function of rigidity sensing in the tumorigenicity of OS cells. Additionally, we quantified the expression of sensor proteins, including four kinases and seven cytoskeletal proteins, in OS cell lines. The upstream core transcription factors of rigidity-sensing proteins were further investigated. We detected anoikis resistance in transformed OS cells. The mechanosensing function of transformed OS cells was also impaired, with general downregulation of rigidity-sensing components. We identified toggling between normal and transformed growth based on the expression pattern of rigidity-sensing proteins in OS cells. We further uncovered a novel TP53 mutation (R156P) in transformed OS cells, which acquired gain of function to inhibit rigidity sensing, thus sustaining transformed growth. Our findings suggest a fundamental role of rigidity-sensing components in OS tumorigenicity as mechanotransduction elements through which cells can sense their physical microenvironment. In addition, the gain of function of mutant TP53 appears to serve as an executor for such malignant programs.

Comparison of the Early Results of Lateral Direct Anterior Approach (L-DAA) and Traditional Posterolateral Approach (PLA) in Hip Arthroplasty.

OBJECTIVE: To evaluate the early results of lateral direct anterior approach (L-DAA) and traditional posterolateral approach (PLA) in hip arthroplasty. METHODS: A total of 24 patients who underwent hip replacement from 2018 to 2021 were divided into PLA group (N = 12) and L-DAA group (N = 12) according to the method of random table number. Outcomes were evaluated between the two groups. RESULTS: The length of incision was shorter; the amount of bleeding was less in the L-DAA group than that in the PLA group. The visual analogue scale (Vas) pain scores for the L-DAA group were significantly lower than that for the PLA group at 24 h, 72 h, and 1 month after operation, and Harris hip scores in the L-DAA group were significantly high in the PLA group at 1 month after operation. In addition, there are no statistically significant differences in acetabular anteversion, abduction, and angle between the two groups. CONCLUSION: L-DAA was superior to PLA for early recovery after hip arthroplasty.

Potency Increase of Spiroketal Analogs of Membrane Inserting Indolyl Mannich Base Antimycobacterials Is Due to Acquisition of MmpL3 Inhibition.

Chemistry campaigns identified amphiphilic indolyl Mannich bases as novel membrane-permeabilizing antimycobacterials. Spiroketal analogs of this series showed increased potency, and the lead compound 1 displayed efficacy in a mouse model of tuberculosis. Yet the mechanism by which the spiroketal moiety accomplished the potency "jump" remained unknown. Consistent with its membrane-permeabilizing mechanism, no resistant mutants could be isolated against indolyl Mannich base 2 lacking the spiroketal moiety. In contrast, mutations resistant against spiroketal analog 1 were obtained in mycobacterial membrane protein large 3 (MmpL3), a proton motive force (PMF)-dependent mycolate transporter. Thus, we hypothesized that the potency jump observed for 1 may be due to MmpL3 inhibition acquired by the addition of the spiroketal moiety. Here we showed that 1 inhibited MmpL3 flippase activity without loss of the PMF, colocalized with MmpL3tb-GFP in intact organisms, and yielded a consistent docking pose within the "common inhibitor binding pocket" of MmpL3. The presence of the spiroketal motif in 1 ostensibly augmented its interaction with MmpL3, an outcome not observed in the nonspiroketal analog 2, which displayed no cross-resistance to mmpL3 mutants, dissipated the PMF, and docked poorly in the MmpL3 binding pocket. Surprisingly, 2 inhibited MmpL3 flippase activity, which may be an epiphenomenon arising from its wider membrane disruptive effects. Hence, we conclude that the potency increase associated with the spiroketal analog 1 is linked to the acquisition of a second mechanism, MmpL3 inhibition. In contrast, the nonspiroketal analog 2 acts pleiotropically, affecting several cell membrane-embedded targets, including MmpL3, through its membrane permeabilizing and depolarizing effects.

Effects of strontium-modified calcium phosphate cement combined with bone morphogenetic protein-2 on osteoporotic bone defects healing in rats.

The objective of the present study was to incorporate strontium into calcium phosphate cement combined with a lower single-dose local administration of bone morphogenetic protein-2 to enhance its in vivo biodegradation and bone tissue growth. After the creation of a rodent critical-sized femoral metaphyseal bone defect, strontium-modified calcium phosphate cement was prepared by mixing sieved granules of calcium phosphate cement and 5% SrCO3 for medical use, and then strontium-modified calcium phosphate cement with dripped bone morphogenetic protein-2 solution (5 µg) was implanted into the defect of OVX rats until death at eight weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, and biomechanics. The results of our study show that a lower single-dose local administration of bone morphogenetic protein-2 combined local usage of strontium-modified calcium phosphate cement can increase the healing of defects in OVX rats. Furthermore, treatments with single-dose local administration of bone morphogenetic protein-2 and strontium-modified calcium phosphate cement showed a stronger effect on accelerating the local bone formation than calcium phosphate cement and strontium-modified calcium phosphate cement used alone. The results from our study demonstrate that combination of a lower single-dose local administration of bone morphogenetic protein-2 and strontium-modified calcium phosphate cement had an additive effect on local bone formation in osteoporosis rats.

Novel Acetamide Indirectly Targets Mycobacterial Transporter MmpL3 by Proton Motive Force Disruption.

To identify novel inhibitors of Mycobacterium tuberculosis cell envelope biosynthesis, we employed a two-step approach. First, we screened the diverse synthetic small molecule 71,544-compound Enamine library for growth inhibitors using the non-pathogenic surrogate Mycobacterium bovis BCG as screening strain and turbidity as readout. Second, 16 confirmed hits were tested for their ability to induce the cell envelope stress responsive promoter piniBAC controlling expression of red fluorescent protein in an M. bovis BCG reporter strain. Using a fluorescence readout, the acetamide E11 was identified. Resistant mutant selection and whole genome sequencing revealed the mycolic acid transporter Mmpl3 as a candidate target of E11. Biochemical analysis using mycobacterial spheroplasts and various membrane assays suggest that E11 indirectly inhibits MmpL3-facilitated translocation of trehalose monomycolates by proton motive force disruption. E11 showed potent bactericidal activity against growing and non-growing M. tuberculosis, low cytotoxic, and hemolytic activity and a dynamic structure activity relationship. In addition to activity against M. tuberculosis, E11 was active against the non-tuberculous mycobacterium M. abscessus, an emerging opportunistic pathogen. In conclusion, we identified a novel bactericidal anti-mycobacterial lead compound targeting MmpL3 providing an attractive starting point for optimization.

[EFFECT OF TIME-RELATED ADMINISTRATION OF METHOTREXATE ON SPINAL CORD INJURY-INDUCED NEURAL CELL APOPTOSIS IN RATS].

OBJECTIVE: To evaluate the effect of time-related administration of methotrexate (MTX) on neural cell apoptosis in rats after spinal cord injury (SCI) so as to investigate its potential neuroprotective mechanism and appropriate administration time. METHODS: A total of 120 male Sprague Dawley rats, 247-286 g in weight, were randomly divided into 4 groups (n=30): sham group (group A), control group (group B), MTX treating group (group C), and MTX prophylaxis group (group D). The SCI model was established in the rats of groups B, C, and D by improved Allen method, and just laminectomy was performed in group A. MTX (0.5 mg/kg) was administered with tail vein injection at 1, 6, 12, 18, and 24 hours after injury in group C, and at 30 minutes before injury and at 6, 12, 18, and 24 hours after injury in group D; the equivalence saline was injected at 1, 6, 12, 18, and 24 hours after injury in groups A and B. Basso-Beattie- Bresnahan (BBB) score was used to evaluate the neural function at 1, 3, 7, 14, and 21 days after injury, HE staining to observe histological changes, immunohistochemical staining and TUNEL method to measure the expression of Caspase-3 and neural cells apoptosis, respectively. RESULTS: Ten rats died during the experiment in groups B, C, and D; 25 rats in each group were included into the experiments at last. BBB score of group A was significantly higher than that of groups B, C, and D at all time points after injury (P<0.05). BBB score of groups C and D were significantly higher than that of group B at 3, 7, 14, and 21 days (P < 0.05), and BBB score of group D was significantly higher than that of group C at 3, 7, and 14 days (P < 0.05). The histological observation showed normal structure of spinal cord at all time points after injury in group A. While the degree of SCI in group D was lighter than that in groups B and C, and group C was lighter than group B. At 14 days after injury, the degree of SCI in groups B, C, and D tend to keep the same. The number of Caspase-3 and TUNEL positive cells of groups B, C, and D was significantly more than that of group A at all time points after injury (P < 0.05), group B was significantly more than groups C and D (P < 0.05). The number of Caspase-3 positive cells of group C was significantly more than that of group D at 3, 7, and 14 days (P < 0.05). While the number of TUNEL positive cells of group C was significantly more than that of group D at 3 and 7 days (P < 0.05). And the number of Caspase-3 positive cells and TUNEL positive cells was positively correlated in groups B, C, and D (P < 0.05) at 1, 3, 7, 14, and 21 days after injury. CONCLUSION: Low-dose MTX may effectively reduce the degree of the secondary injury of spinal cord by reducing the nerve cell apoptosis. Better effect can be obtained when MTX is used as prevent method than as a way of treatment.

Inhibition of inflammatory cytokines after early decompression may mediate recovery of neurological function in rats with spinal cord injury.

A variety of inflammatory cytokines are involved in spinal cord injury and influence the recovery of neuronal function. In the present study, we established a rat model of acute spinal cord injury by cerclage. The cerclage suture was released 8 or 72 hours later, to simulate decompression surgery. Neurological function was evaluated behaviorally for 3 weeks after surgery, and tumor necrosis factor α immunoreactivity and apoptosis were quantified in the region of injury. Rats that underwent decompression surgery had significantly weaker immunoreactivity of tumor necrosis factor α and significantly fewer apoptotic cells, and showed faster improvement of locomotor function than animals in which decompression surgery was not performed. Decompression at 8 hours resulted in significantly faster recovery than that at 72 hours. These data indicate that early decompression may improve neurological function after spinal cord injury by inhibiting the expression of tumor necrosis factor α.

Identification of differentially expressed microRNAs involved in non-traumatic osteonecrosis through microRNA expression profiling.

Accumulating evidence has recently indicated a vital role of microRNAs (miRNAs) in the development of various bone diseases. However, the biological role of miRNAs in the pathogenesis of non-traumatic osteonecrosis of femoral head (ONFH) has not yet been investigated. The present study aimed to profile the differential miRNA expression between non-traumatic ONFH and femoral neck fracture and to develop further understanding of the molecular mechanisms involved in the pathogenesis of non-traumatic ONFH. Femoral heads from 4 patients with non-traumatic ONFH and 4 with femoral neck fracture were used to analyze the miRNA expression profiles in bone tissue using the Exiqon miRCURY™ LNA Array (v.18.0). The results of miRNA microarray analysis were further confirmed by real-time quantitative polymerase chain reaction (qPCR). The differentially expressed miRNA target genes and signaling pathways involved were predicted by bioinformatics analysis. MiRNA microarray chip analysis revealed that 22 miRNAs were significantly up-regulated and 17 were significantly down-regulated in the non-traumatic ONFH samples compared with the femoral neck fracture samples. The real-time qPCR also confirmed the microarray data. Bioinformatics analysis demonstrated that toll-like receptor (TLR), neurotrophin and NOD-like receptor signaling pathway were most likely to be regulated by these differential miRNAs. This miRNA microarray study reveals significant differences in miRNA expression between patients with non-traumatic ONFH and those with femoral neck fracture. Our data also manifests that the signaling pathways regulated by these differentially expressed miRNAs might be important in the pathogenesis of non-traumatic ONFH.

[Posterior short-segment fixation with undermining decompress for upper lumbar burst fractures].

OBJECTIVE: To observe clinical effects of posterior short-segment fixation with undermining decompress by posterior ligament complex for the treatment of upper lumbar burst fractures. METHODS: From October 2010 to March 2013,23 patients with upper lumbar burst fractures (Denis B type) were treated by posterior short-segment fixation with undermining decompress by posterior ligament complex. There were 18 males and 5 females aged from 26 to 64 years old with an average of 45.7 years old. Twelve patients were caused by falling down, 5 cases were caused by traffic accident, 4 cases were the bruise injury caused by heavy object and 2 cases were caused by other injury. Fourteen patients were L1 fracture and 9 patients were L2 fracture. Thirteen patients were combined with nerve injuries (degree D according to ASIA classification). Internal fixation were removed from 12 to 20 months with an average of 14.3 months. JOA scores and imaging changes were recorded and compared at different time points. RESULTS: All patients were followed up from 18 to 24 months with an average of 20.4 months. Thirteen patients with nerve injuries were completely recovered at 3 to 6 months after operation. JOA score at 1 year after operation was 20.63 ± 0.92, and 20.38 ± 1.06 at 3 months after removal of internal fixation,which were improved obviously than 9.90 ± 2.73 at 3 months after operation. (P > 0.05) Anterior height of injured vertebrae, vertebral body angle and local Cobb angle was (95.0 ± 0.53)%, (2.78 ± 1.36) and (2.43 ± 1.52) °respectively, and improved obviously than that of before operation (P < 0.05). There was no statistical significance in JOA scores at 3 months after removal of internal fixation and 1 year after operation (P > 0.05). CONCLUSION: posterior short-segment fixation with undermining decompress by posterior ligament complex for the treatment of upper lumbar burst fractures has advantages of minimally invasive, could effective recover vertebrae height, maintain stability of spine, decrease low back pain. It is a safe and effective operative method.

The cell death and DNA damages caused by the Tet-On regulating HSV-tk/GCV suicide gene system in MCF-7 cells.

Ganciclovir (GCV) affects the molecular mechanism of cell death and DNA damage by the rAAV (recombinant adeno-associated virus)-mediated Tet-On/HSV-tk/GCV suicide gene system in human breast cancer cell line MCF-7. A rAAV/TRE/Tet-On/HSV-tk combining a Tet-On regulating system and a suicide gene HSV-tk was used to transfect human breast cancer cell line MCF-7, and therapeutic effects on this system were studied. Afterwards, we used RT-PCR, western blotting, and a modified comet-assay to explore the potential mechanism of the HSV-tk/GCV suicide gene system in breast cancer treatments. MTT assay has shown that the cell number of GCV+rAAV+Dox group was significantly decreased compared with that of other groups after treatment and flow cytometric analysis detected that there was a substantial increase of S phase cells in this group, which means the HSV-tk/GCV suicide gene system probably works on the cell cycle. RT-PCR detected the expression level of p21 increased and PCNA had an opposite trend. Western blotting detected the protein expression of p21 and p53 increased and PCNA, CDK1, cyclin B decreased in GCV+rAAV+Dox group. The modified comet-assay shown that the very small extra fragments generated by the GCV+rAAV+Dox group treatment are visible as a small cloud extending from the comet in the direction of electrophoresis. The therapeutic mechanism of the HSV-tk/GCV suicide gene system on human breast cancer cell line MCF-7 is probably by upregulating the expression of p21 through a p53-dependent DNA damage signalling pathway, leading the decrease of protein expression of PCNA, cyclin B, CDK1 in MCF-7 cells and promoting the cell cycle arrest at G1/S phase. In summary, the HSV-tk/GCV suicide gene system arouses the death of MCF-7 cells from blocking the cell cycle and DNA damage.