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BACKGROUND: Brachydactyly type E (BDE) is a general term characterized by variable shortening of metacarpals and metatarsals, with phalanges affected frequently. It can occur as an isolated form or part of syndromes and manifest a high degree of phenotypic variability. In this study, we have identified the clinical characteristics and pathogenic causes of a four-generation pedigree with 10 members affected by BDE and short stature. METHODS: After the informed consent was signed, clinical data and peripheral blood samples were collected from available family members. Karyotype analysis, array-CGH, next-generation sequencing, and Sanger sequencing were employed to identity the pathogenic candidate gene. RESULTS: No translocation or microdeletion/duplication was found in karyotype analysis and array-CGH; hence, a novel heterozygous mutation, c.146dupA. p.S50Vfs*22, was detected by next-generation sequencing in PTHLH gene, leading to a premature stop codon. Subsequently, the mutation was confirmed by Sanger sequencing and co-segregation analysis. CONCLUSION: In this study, we described a novel heterozygous mutation (c.146dupA. p.S50Vfs*22) of gene PTHLH in a Chinese family. The mutation could induce a premature stop codon leading to a truncation of the protein. Our study broadened the mutation spectrum of PTHLH in BDE.
Subject(s)
Brachydactyly , Dwarfism , Humans , Brachydactyly/genetics , Codon, Nonsense , Mutation , Parathyroid Hormone-Related Protein/geneticsABSTRACT
Continuous real-time location data is very important in the big data era, but the privacy issues involved is also a considerable topic. It is not only necessary to protect the location privacy at each release moment, but also have to consider the impact of data correlation. Correlated Laplace Mechanism (CLM) is a sophisticated method to implement differential privacy on correlated time series. This paper aims to solve the key problems of applying CLM in continuous location release. Based on the finding that the location increment is approximately stationary in many scenarios, a location correlation estimation method based on the location increment is proposed to solve the problem of nonstationary location data correlation estimation; an adaptive adjustment model for the CLM filter based on parameter quantization idea (QCLM) as well as its effective implementation named QCLM-Lowpass utilizing the lowpass spectral characteristics of location data series is proposed to solve the problem of output deviations due to the undesired transient response of the CLM filter in time-varying environments. Extensive simulations and real data experiments validate the effectiveness of the proposed approach and show that the privacy scheme based on QCLM-Lowpass can offer a better balance between the ability to resist correlation-based attacks and data availability.
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BACKGROUND: Finite element analysis (FEA) was performed to investigate the biomechanical differences between different adjunct fixation methods for oblique lumbar interbody fusion (OLIF) and to further analyze its effect on adjacent segmental degeneration. METHODS: We built a single-segment (Si-segment) finite element model (FEM) for L4-5 and a double-segment (Do-segment) FEM for L3-5. Each complete FEM was supplemented and modified, and both developed two surgical models of OLIF with assisted internal fixation. They were OLIF with posterior bilateral percutaneous pedicle screw (TINA system) fixation (OLIF + BPS) and OLIF with lateral plate system (OLIF + LPS). The range of motion (ROM) and displacement of the vertebral body, cage stress, adjacent segment disc stress, and spinal ligament tension were recorded for the four models during flexion/extension, right/left bending, and right/left rotation by applying follower load. RESULTS: For the BPS and LPS systems in the six postures of flexion, extension, right/left bending, and right/left rotation, the ROM of L4 in the Si-segment FEM were 0.32°/1.83°, 0.33°/1.34°, 0.23°/0.47°, 0.24°/0.45°, 0.33°/0.79°, and 0.34°/0.62°; the ROM of L4 in the Do-segment FEM were 0.39°/2.00°, 0.37°/1.38°, 0.23°/0.47°, 0.21°/0.44°, 0.33°/0.57°, and 0.31°/0.62°, and the ROM of L3 in the Do-segment FEM were 6.03°/7.31°, 2.52°/3.50°, 4.21°/4.38°, 4.21°/4.42°, 2.09°/2.32°, and 2.07°/2.43°. BPS system had less vertebral displacement, less cage maximum stress, and less spinal ligament tension in Si/Do-segment FEM relative to the LPS system. BPS system had a smaller upper adjacent vertebral ROM, greater intervertebral disc stress in terms of left and right bending as well as left and right rotation compared to the LPS system in the L3-4 of the Do-segment FEM. There was little biomechanical difference between the same fixation system in the Si/Do-segment FEM. CONCLUSIONS: Our finite element analysis showed that compared to OLIF + LPS, OLIF + BPS (TINA) is more effective in reducing interbody stress and spinal ligament tension, and it better maintains the stability of the target segment and provides a better fusion environment to resist cage subsidence. However, OLIF + BPS (TINA) may be more likely to cause adjacent segment degeneration than OLIF + LPS.
Subject(s)
Pedicle Screws , Spinal Fusion , Humans , Finite Element Analysis , Lipopolysaccharides , Lumbar Vertebrae/surgery , Spinal Fusion/methods , Biomechanical Phenomena , Range of Motion, ArticularABSTRACT
The abuse of antibiotics leads to an increasing emergence of drug-resistant bacteria, which not only causes a waste of medical resources but also seriously endangers people's health and life safety. Therefore, it is highly desirable to develop an efficient antibacterial strategy to reduce the reliance on traditional antibiotics. Antibacterial photodynamic therapy (aPDT) is regarded as an intriguing antimicrobial method that is less likely to generate drug resistance, but its efficiency still needs to be further improved. Herein, a robust titanium-based metal-organic framework ACM-1 was adopted to support Ag nanoparticles (NPs) to obtain Ag NPs@ACM-1 for boosting antibacterial efficiency via synergistic chemical-photodynamic therapy. Apart from the intrinsic antibacterial nature, Ag NPs largely boost ROS production and thus improve aPDT efficacy. As a consequence, Ag NPs@ACM-1 shows excellent antibacterial activity under visible light illumination, and its minimum bactericidal concentrations (MBCs) against E. coli, S. aureus, and MRSA are as low as 39.1, 39.1, and 62.5 µg mL-1, respectively. Moreover, to expand the practicability of Ag NPs@ACM-1, two (a dense and a loose) Ag NPs@ACM-1 films were readily fabricated by simply dispersing Ag NPs@ACM-1 into heated aqueous solutions of edible agar and sequentially cooling through heating or freeze-drying, respectively. Notably, these two films are mechanically flexible and exhibit excellent antibacterial activities, and their antimicrobial performances can be well retained in their recyclable and remade films. As agar is nontoxic, degradable, inexpensive, and ecosustainable, the dense and loose Ag NPs@ACM-1 films are potent to serve as recyclable and degradable antibacterial plastics and antibacterial dressings, respectively.
Subject(s)
Anti-Infective Agents , Metal Nanoparticles , Metal-Organic Frameworks , Photochemotherapy , Humans , Silver/pharmacology , Titanium/pharmacology , Metal-Organic Frameworks/pharmacology , Staphylococcus aureus , Escherichia coli , Agar , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity TestsABSTRACT
BACKGROUND: Nickel-Titanium shape-memory sawtooth-arm embracing clamps (SSECs) have been used in revision total hip arthroplasties (rTHAs) to protect stem stability. This study was to introduce this technique and report its mid to long-term clinical and radiographic outcomes. METHODS: We retrospectively reviewed all patients implanted with SSECs in our department from January 2008 to December 2015. 41 patients (41 hips) were finally included. Radiographs and Harris hip scores (HHS) were collected. Radiographs were blindly analyzed for evidence of loosening, subsidence and stress shielding. HHS were compared to previous records by student's t tests. The average follow-up period was 9.3 years. RESULTS: All stems were stably fixed with no signs of loosening. The mean stem subsidence was 0.9 mm (range, 0 to 3 mm). Only one patient (2.4%) demonstrated the fourth degree of stress shielding, with the others none or minor bone resorption. The mean HHS at the final follow-up was 84.2 (range, 81 to 91), which was improved from 17.4 (range, 0 to 37) before surgery. No implant failures or re-revisions occurred. Dislocation occurred in 1 case during the follow-up period. CONCLUSIONS: The SSEC protected stem fixation and achieved favorable clinical and radiographic outcomes in this 9-year follow-up study. It offered an additional extramedullary fixation option for surgeons to choose from in treating complex femoral revision arthroplasties.
Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Humans , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/methods , Follow-Up Studies , Retrospective Studies , Prosthesis Design , Reoperation , Prosthesis Failure , Treatment OutcomeABSTRACT
Patients with OA and varus knees are subject to abnormal mechanical environment and objective of this study was to investigate the molecular mechanisms underlying chondrocyte senescence caused by mechanical overloading and the role of Zmpste24-mediated nuclear membrane instability in varus knees. Finite element analysis showed that anteromedial region of tibial plateau experienced the most mechanical stress in an osteoarthritis patient with a varus knee. Immunohistochemistry exhibited lower Zmpste24 expression and higher expression of senescence marker p21 in the anteromedial region. Animal experiments and cell-stretch models also demonstrated an inverse relationship between Zmpste24 and mechanically induced senescence. Zmpste24 overexpression rescued cartilage degeneration and senescence in vitro by scavenging ROS. In conclusion, anteromedial tibial plateau is exposed to abnormal stress in varus knees, downregulation of Zmpste24, and nuclear membrane stability may explain increased senescence in this region. Zmpste24 and nuclear membrane stability are potential targets for treating osteoarthritis caused by abnormal alignment.
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A basic understanding of delayed packet loss is key to successfully applying it to multi-node hopping networks. Given the problem of delayed data loss due to network delay in a hop network environment, we review early time windowing approaches, for which most contributions focus on end-to-end hopping networks. However, they do not apply to the general hopping network environment, where data transmission from the sending host to the receiving host usually requires forwarding at multiple intermediate nodes due to network latency and network cache overflow, which may result in delayed packet loss. To overcome this challenge, we propose a delay time window and a method for estimating the delay time window. By examining the network delays of different data tasks, we obtain network delay estimates for these data tasks, use them as estimates of the delay time window, and validate the estimated results to verify that the results satisfy the delay distribution law. In addition, simulation tests and a discussion of the results were conducted to demonstrate how to maximize the reception of delay groupings. The analysis shows that the method is more general and applicable to multi-node hopping networks than existing time windowing methods.
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Differential privacy (DP) has become a de facto standard to achieve data privacy. However, the utility of DP solutions with the premise of privacy priority is often unacceptable in real-world applications. In this paper, we propose the best-effort differential privacy (B-DP) to promise the preference for utility first and design two new metrics including the point belief degree and the regional average belief degree to evaluate its privacy from a new perspective of preference for privacy. Therein, the preference for privacy and utility is referred to as expected privacy protection (EPP) and expected data utility (EDU), respectively. We also investigate how to realize B-DP with an existing DP mechanism (KRR) and a newly constructed mechanism (EXPQ) in the dynamic check-in data collection and publishing. Extensive experiments on two real-world check-in datasets verify the effectiveness of the concept of B-DP. Our newly constructed EXPQ can also satisfy a better B-DP than KRR to provide a good trade-off between privacy and utility.
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This study aims to explore the influence mechanism of personal initiative on the overall emergency management ability of enterprises so as to put forward effective measures to improve the emergency management ability. Based on social interaction theory and feature activation theory, the concepts of organizational support theory, executive power, and political skills were introduced to construct a corresponding theoretical model. We collected data through an online questionnaire to test this model via structural equation model analysis and regression analysis, with 208 participants of varying backgrounds. The results show that personal initiative can strengthen enterprise emergency management ability. The mediating effect of executive power between personal initiative and emergency management ability of enterprise has also been proved. In addition, the two adjustment variables of political skills and perceived organizational support both have a positive impact on the improvement of personal initiative and execution. Therefore, in order to improve the enterprise emergency management ability, it is suggested that enterprises should give full play to the personal initiative and improve the individual and overall executive power. The conclusion of this paper can provide new methodological support for improving emergency management ability.
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We sought to investigate the outcomes of posterior-only approach using polyetheretherketone (PEEK) cage combined with single-segment instrumentation (modified-approach) for mono-segment lumbar tuberculosis in children. Between February 2008 and August 2017 in our hospital, 18 children with single-segment lumbar tuberculosis enrolled in this study were treated by modified-approach. Medical records and radiographs were retrospectively analyzed. Mean follow-up time was 54.6 ± 12.1 months. No severe complications were noted to have occurred. Measures indicated there was satisfactory bone fusion for all patients. Mean Cobb angles were significantly decreased from preoperative angle (19.8° ± 13.1°) to those both postoperatively (- 4.9° ± 7.6°) and at final follow-up (- 3.5° ± 7.3°) (both P < 0.05), with a mean angle loss of 1.7° ± 0.9°. The erythrocyte sedimentation rate (ESR) returned to normal levels for all patients within 3 months postoperatively. All patients had significant postoperative improvement in neurological performance. The modified-approach was an effective and feasible treatment option for mono-segment children with lumbar tuberculosis. Such procedures can likely help patients by increasing retainment of lumbar mobility and reducing invasiveness.
Subject(s)
Benzophenones/therapeutic use , Lumbar Vertebrae/surgery , Lumbosacral Region/surgery , Polymers/therapeutic use , Tuberculosis, Spinal/surgery , Adolescent , Child , Female , Humans , Male , Postoperative Period , Radiography/methods , Plastic Surgery Procedures/methods , Retrospective Studies , Spinal Fusion/methods , Thoracic Vertebrae/surgery , Treatment OutcomeABSTRACT
Metastatic castration-resistant prostate cancer (mCRPC) is the lethal stage and the leading cause of death in prostate cancer patients, among which bone metastasis is the most common site. Here in this article, we downloaded the gene expression data and clinical information from online dataset. We found that prostate cancer metastasis in bone is prone to have higher prostate-specific antigen (PSA) and longer time on first-line androgen receptor signaling inhibitors (ARSI). A total of 1,263 differentially expressed genes (DEGs) were identified and results of functional enrichment analysis indicated the enrichment in categories related to cell migration, cancer related pathways and metabolism. We identified the top 20 hub genes from the PPI network and analyzed the clinical characteristics correlated with these hub genes. Finally, we analyzed the immune cell abundance ratio of each sample in different groups. Our results reveal the different clinical characteristics, the immune cell infiltration pattern in different sites of mCRPC, and identify multiple critical related genes and pathways, which provides basis for individualized treatment.
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Osteosarcoma is the most prevalent primary bone malignancy in adolescents, and ferroptosis is implicated in its pathogenesis. MicroRNA (miR)-1287-5p plays critical roles in multiple human cancers, and the present study aims to investigate the role and underlying mechanisms of miR-1287-5p in regulating ferroptosis and osteosarcoma progression. Human osteosarcoma cell lines were treated with the mimic, inhibitor or matched controls of miR-1287-5p. Cell viability, colony formation, cell death ratio and ferroptosis were determined. miR-1287-5p expression was downregulated in human osteosarcoma, but upregulated upon ferroptotic stimulation. Overexpression of miR-1287-5p significantly induced, while inhibition of miR-1287-5p suppressed ferroptosis of osteosarcoma cells, thereby modulating cell viability and colony formation. Mechanistic studies indicated that miR-1287-5p directly bound to the 3'-untranslated region of glutathione peroxidase 4 (GPX4) to inhibit its protein level and activity, and that GPX4 overexpression completely abolished the miR-1287-5p mimic-mediated ferroptotic induction and tumor suppression. Moreover, the miR-1287-5p mimic dramatically sensitized human osteosarcoma cells to cisplatin chemotherapy. Our findings prove that miR-1287-5p promotes ferroptosis of osteosarcoma cells through inhibiting GPX4, identifying an adjuvant and even alternative method for the treatment of human osteosarcoma.
Subject(s)
Bone Neoplasms , Ferroptosis , MicroRNAs , Osteosarcoma , Bone Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Cisplatin/pharmacology , Ferroptosis/genetics , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Osteosarcoma/geneticsABSTRACT
The social system can spread tightly coupled complex practices under the context that members of the social system do not have the shared experience that enables them to coordinate within longstanding tight formal organizations. To promote the understanding of such a process, and given the possibility for other members in the social system to cheat and adopt pro-environment behavior, we draw on the organizational justice literature and the perspective of justice enforceability, and construal level theory, to develop a conceptual model in which the impact of social members' perceived psychological distance on their response to other social members adoption of pro-environmental behaviors (PEBs) is contingent on their perception of justice enforceability and cognitive appraisals (positive, not significant) towards other social members' adoption of PEBs. We find that when social members perceive that the adoption of pro-environment behaviors is justice-enforceable, their cognitive appraisals of other social members' adoption of PEBs is high, and then the more proximal the psychological distance they perceive, the stronger they will react to other social members' adoption of PEBs. Further, they will adopt and enact such behaviors, otherwise, they would be unwilling to adopt and enact such behaviors. So, uneven perceived psychological distance of social members can harm their adoption and the spread of pro-environment behavior. We tested our model in a survey study. Results show that the proposed model is supported, and our understanding is enhanced about how social members' willingness to adopt and spread pro-environment behavior is contingent on their perceptions of justice enforceability. This paper is comprised of five parts, of which include an introduction, a part on the theory and hypothesis, data and methods, results and discussion, and conclusion.
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The neuroinflammation following traumatic spinal cord injury (SCI) is a critical process that impacts both the injury and the recovery of spinal cord parenchyma. Infiltrating regulatory T (Treg) cells are potent anti-inflammatory cells that restrain post-SCI neuroinflammation. To understand the molecular mechanisms underlying the activity of infiltrating Treg cells, we used a mouse spinal cord compression injury model to analyze the role of Sirtuins (SIRTs) in the modulation of infiltrating Treg cell functions. We found that the expressions of SIRT4 and SIRT6 were up-regulated in infiltrating Treg cells. Using lentivirus-mediated gene expression or RNA interference, we revealed that SIRT4 substantially inhibited the expression of Foxp3, interleukin-10, and transforming growth factor-ß in Treg cells, whereas SIRT6 had little effect on Treg cells. Consistently, SIRT4 overexpression weakened the suppressive effect of Treg cells on lipopolysaccharide-stimulated spinal cord CD11b+ myeloid cells. Knock-down of SIRT4 enhanced the anti-inflammatory activity of infiltrating Treg cells in the parenchyma of injured spinal cords. Additionally, SIRT4 overexpression blocked in vitro Treg cell generation from conventional T cells. Furthermore, SIRT4 down-regulated 5' AMP-activated protein kinase (AMPK) signaling in Treg cells, whereas the AMPK agonist AICAR restored the expression of Foxp3 and interleukin-10 in SIRT4-overexpressing Treg cells. In conclusion, our research unveils a new mechanism by which the post-SCI neuroinflammation is regulated.
Subject(s)
Forkhead Transcription Factors/metabolism , Mitochondrial Proteins/metabolism , Sirtuins/metabolism , Spinal Cord Injuries/metabolism , T-Lymphocytes, Regulatory/immunology , Adenylate Kinase/metabolism , Animals , Cells, Cultured , Disease Models, Animal , Forkhead Transcription Factors/genetics , Humans , Lymphocyte Activation , Mice , Mice, Inbred C57BL , Mice, Transgenic , Mitochondrial Proteins/genetics , Neurogenic Inflammation , RNA, Small Interfering/genetics , Signal Transduction , Sirtuins/genetics , Spinal Cord Injuries/immunology , Up-RegulationABSTRACT
OBJECTIVE: To compare the cervical sagittal balance and surgical outcomes between anterior cervical discectomy and fusion (ACDF) and hybrid decompression and fusion (HDF; 1-level corpectomy combined with 1-level discectomy) for consecutive 3-level cervical spondylotic myelopathy (CSM). METHODS: From January 2013 to June 2016, 82 patients with 3-level CSM who underwent ACDF (n = 40) and HDF (n = 42) were retrospectively reviewed. Perioperative parameters, clinical outcomes, and radiologic sagittal alignment were analyzed and compared. RESULTS: Patients were followed up for 35.5 ± 6.5 months (range, 25-53 months). All patients had achieved significant improvement in Neck Disability Index and Japanese Orthopedic Association scores after operation, with similar clinical outcomes between both groups (P > 0.05). In the ACDF group, 2 patients were found with axial symptoms, and 1 with hoarseness. In the HDF group, 5 patients were found with axial symptoms, 1 with hoarseness, 1 with dysphagia, and 1 with pseudarthrosis. The ACDF group had less operation time and bleeding compared with the HDF group (P < 0.05). The restoration of segmental and C2-7 lordosis were significantly greater in the ACDF group than the HDF group (P < 0.05). The C2-7 sagittal vertical axis and T1 slope minus C2-7 lordosis decreased in the ACDF group at final follow-up (P < 0.05); however, there was no obvious change in those of the HDF group (P > 0.05). CONCLUSIONS: Both ACDF and HDF were safe and effective for the treatment of 3-level CSM. ACDF showed superiority to HDF in terms of less blood loss, shorter operation time, and better postoperative sagittal balance.
Subject(s)
Decompression, Surgical/methods , Diskectomy/methods , Spinal Cord Diseases/surgery , Spinal Fusion/methods , Spondylosis/surgery , Adult , Aged , Bone Plates , Disability Evaluation , Female , Humans , Lordosis/surgery , Male , Middle Aged , Operative Time , Retrospective Studies , Spondylosis/diagnostic imaging , Treatment OutcomeABSTRACT
OBJECTIVE: To assess whether preoperative T1 slope and cervical lordosis mismatching affect the surgical outcomes of patients with cervical spondylotic myelopathy (CSM) after laminoplasty. METHODS: A total of 85 patients with CSM who underwent unilateral open-door laminoplasty between January 2013 and May 2017 were retrospectively reviewed. Based on preoperative T1 slope and C2-C7 lordosis matching, the patients were divided into 2 groups: the match group and the mismatch group. The T1 slope minus C2-C7 lordosis (T1S-CL) <20° was defined as matching. Radiographic parameters included T1 slope, C2-C7 lordosis, C2-C7 sagittal vertical axis (SVA), and T1S-CL. Clinical outcomes were based on the Neck Disability Index (NDI) and Japanese Orthopedic Association (JOA) scores. RESULTS: The preoperative T1S-CL had significant correlation with T1 slope (r = 0.283), C2-C7 lordosis (r = -0.611), and C2-C7 SVA (r = 0.331). At the final follow-up, patients in the mismatch group had a higher incidence of postoperative cervical kyphosis (P = 0.007) and C2-C7 SVA >40 mm (P = 0.043). The mismatch group also had greater â³C2-C7 lordosis (P = 0.028), â³C2-C7 SVA (P = 0.042), and â³T1S-CL (P = 0.044). Comparison of clinical outcomes revealed that patients in the match group had better NDI and JOA recovery (P < 0.05). CONCLUSIONS: T1S-CL is a clinically relevant parameter for surgical decision making because patients with T1S-CL mismatching are more likely to have postoperative kyphotic alignment changes and cervical sagittal imbalance. Laminoplasty might not be a suitable option for patients with T1S-CL mismatching.
Subject(s)
Cervical Vertebrae/diagnostic imaging , Laminoplasty/trends , Lordosis/diagnostic imaging , Preoperative Care/methods , Spondylosis/diagnostic imaging , Adult , Aged , Cervical Vertebrae/surgery , Female , Follow-Up Studies , Humans , Laminoplasty/methods , Lordosis/surgery , Male , Middle Aged , Retrospective Studies , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/surgery , Spondylosis/surgery , Treatment OutcomeABSTRACT
Clofazimine (CFZ) is a promising candidate drug for use in the management of multidrug-resistant tuberculosis (MDR-TB) patients. In this study, the minimum inhibitory concentration (MIC) method and checkerboard method were used to investigate potential synergies between CFZ and moxifloxacin (MOX) or capreomycin (CAP). Thirty Mycobacterium tuberculosis strains were collected, including 13 MDR strains, 2 extensively drug-resistant (XDR) strains, 3 pan-sensitive strains and 12 strains resistant to other drugs. When the minimum fractional inhibitory concentration indexes (FICIs) were calculated, synergy was found in 21 (70.00%) M. tuberculosis strains against the CFZ/CAP combination and 29 (96.67%) against the CFZ/MOX combination. When the maximum FICIs were calculated, 10 of 15 MDR/XDR strains and 2 of 15 other drug-resistant or pan-sensitive strains showed antagonism against the CFZ/CAP combination, whilst 8 of 15 MDR/XDR strains and 1 of 15 other drug-resistant or pan-sensitive strains showed antagonism against the CFZ/MOX combination, respectively. In conclusion, these findings demonstrate that the combination of CFZ and MOX shows better synergism than the combination of CFZ and CAP. The MDR/XDR isolates are more likely to show antagonism than the other drug-resistant or pan-sensitive strains in both the CFZ/MOX and CFZ/CAP combinations. CFZ in combination with MOX may be a promising drug regimen for the treatment of MDR-TB, particularly for susceptible M. tuberculosis infections.
Subject(s)
Antitubercular Agents/therapeutic use , Capreomycin/therapeutic use , Clofazimine/therapeutic use , Moxifloxacin/therapeutic use , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , China , Drug Synergism , Drug Therapy, Combination/methods , Humans , Microbial Sensitivity Tests , Mycobacterium tuberculosis/isolation & purificationABSTRACT
DESIGN: This a retrospective study in single centre. OBJECTIVE: The objective of this retrospective clinical study is to compare the long-term clinical efficacy of posterior long-segment and short-segment fixation with single-stage transpedicular debridement and fusion for the treatment of thoracolumbar spinal tuberculosis in adults. METHODS: Sixty-six cases of thoracolumbar tuberculosis were treated by single-stage transpedicular debridement, bone graft fusion, and pedicle screw fixation. Thirty-five cases were under long-segment fixation (group A) and 31 cases were under short-segment fixation (group B). These patients were followed up for a minimum of five years. The clinical and radiographic results for these patients were analyzed and compared. RESULTS: All 66 patients were completely cured during the follow-up. All patients had significant improvement of neurological condition and visual analogue scale pain scores at the final follow-up. The average operation duration and blood loss in group A were more than that in group B. Kyphosis Cobb angle of both groups was significantly corrected after surgical management. The correction rate of Cobb angle in group A was significantly higher than that in group B at the time of immediate post-operative period or the last follow-up (P < 0.05). The correction loss of group A was significantly less than that in group B (P < 0.05). CONCLUSION: Both posterior long-segment and short-segment pedicle screw fixations for the treatment of thoracolumbar spinal tuberculosis have significant effects in the correction of kyphosis and the improvement of neurological function. Although the blood loss and operation time of long-segment fixation were more than that of short-segment fixation, long-segment fixation was superior to the short-segment fixation in the correction of kyphosis and the maintenance of spinal stability, especially in the prevention of long-term correction loss.
Subject(s)
Debridement/methods , Fracture Fixation, Internal/methods , Spinal Fusion/methods , Tuberculosis, Spinal/surgery , Adult , Aged , Debridement/adverse effects , Female , Follow-Up Studies , Fracture Fixation, Internal/adverse effects , Humans , Kyphosis/surgery , Lumbar Vertebrae/surgery , Male , Middle Aged , Operative Time , Pedicle Screws/adverse effects , Retrospective Studies , Spinal Fusion/adverse effects , Thoracic Vertebrae/surgery , Treatment Outcome , Tuberculosis, Spinal/complications , Young AdultABSTRACT
Wip1 has been shown to correlate with the metastasis/invasion of several tumors. This study was designed to investigate the clinical significance and biological function of Wip1 in intrahepatic cholangiocarcinoma (ICC). The expression of Wip1 was investigated in sixty human ICC biopsy samples by immunohistochemistry. Transient and stable knockdown of Wip1 in two human ICC cells (ICC-9810 and SSP25) were established using short hairpin RNA expression vector. Immunohistochemistry revealed that Wip1 was up-regulated in human ICC tissues (47/60, 78.3%). High levels of Wip1 in human ICC correlated with metastasis to the lymph metastasis (P=0.022). Genetic depletion of Wip1 in ICC cells resulted in significantly inhibited proliferation and invasion compared with controls. Most importantly, Wip1 down-regulation impaired tumor migration capacity of ICC cells in vivo. Subsequent investigations revealed that matrix metalloproteinase-2 (MMP-2) is an important target of Wip1. Consistently, in human ICC tissues, Wip1 level was positively correlated with MMP-2 expression. Taken together, our founding indicates that Wip1 may be a crucial regulator in the tumorigenicity and invasion of human ICC, Wip1 exerts its pro-invasion function at least in part through the MMP-2 signaling pathway, suggesting Wip1 as a potential therapeutic target for ICC.
ABSTRACT
BACKGROUND: The aim of this paper was to retrospectively analyze the clinical efficacy and feasibility of thoracic and lumbar spinal tuberculosis treated by single-stage posterior debridement, interbody fusion with titanium mesh cages (TMC), and combined short-segment instrumentation. METHODS: Fifteen patients with no more than two vertebral bodies involving thoracic and lumbar tuberculosis were collected from January 2006 to January 2010, performed by single-stage posterior debridement, interbody fusion with TMC and posterior short-segment fixation. The clinical efficacy was evaluated based on the data of the 10-point Visual Analogue Scale (VAS), neurological status, kyphosis angle, erythrocyte sedimentation rate, and C-reactive protein, which were collected at a certain time. RESULTS: The average duration of surgery was 135 minutes. All the patients were followed up for a period ranging from 18 to 48 months (mean 28.9±6.44 months). The VAS score was improved from 8.47±1.13 (range 7-10) before surgery to 2.1±1.7 (range 0-2) after surgery. Correction of segmental kyphotic deformity was 24.2±6.59°. Neither the postoperative change of the position of titanium mesh cage nor any posterior instrumentation failure was recorded. The situation of 13 patients with incomplete neurologic lesions before surgery was improved after surgery. CONCLUSIONS: Patients with thoracic and lumbar spinal tuberculosis can be successfully treated by posterior debridement, interbody fusion with TMC combining short-segment instrumentation. The presence of the TMC anteriorly at the site of tubercular spondylitis has no negative influence on the course of infection healing, and additionally they stabilize the affected segment maintaining sufficient sagittal profile.