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Neuroblastoma (NB), as the most common extracranial solid tumor in childhood, is one of the critical culprits affecting children's health. Given the heterogeneity and invisibility of NB tumors, the existing diagnostic and therapeutic approaches are inadequate and ineffective in early screening and prognostic improvement. With the rapid innovation and development of nanotechnology, nanomedicines have attracted widespread attention in the field of oncology research for their excellent physiological and chemical properties. In this review, we first explored the current common obstacles in the diagnosis and treatment of NB. Then we comprehensively summarized the advancements in nanotechnology-based multimodal synergistic diagnosis and treatment of NB and elucidate the underlying mechanisms. In addition, a discussion of the pending challenges in biocompatibility and toxicity of nanomedicine was conducted. Finally, we described the development and application status of nanomaterials against some of the recognized targets in the field of NB research, and pointed out prospects for nanomedicine-based precision diagnosis and therapy of NB. [ABSTRACT FROM AUTHOR]

Accurate and rapid diagnosis of COVID-19 suspected cases plays a crucial role in timely quarantine and medical treatment. Developing a deep learning-based model for automatic COVID-19 diagnosis on chest CT is helpful to counter the outbreak of SARS-CoV-2. A weakly-supervised deep learning framework was developed using 3D CT volumes for COVID-19 classification and lesion localization. For each patient, the lung region was segmented using a pre-trained UNet; then the segmented 3D lung region was fed into a 3D deep neural network to predict the probability of COVID-19 infectious; the COVID-19 lesions are localized by combining the activation regions in the classification network and the unsupervised connected components. 499 CT volumes were used for training and 131 CT volumes were used for testing. Our algorithm obtained 0.959 ROC AUC and 0.976 PR AUC. When using a probability threshold of 0.5 to classify COVID-positive and COVID-negative, the algorithm obtained an accuracy of 0.901, a positive predictive value of 0.840 and a very high negative predictive value of 0.982. The algorithm took only 1.93 seconds to process a single patient’s CT volume using a dedicated GPU. Our weakly-supervised deep learning model can accurately predict the COVID-19 infectious probability and discover lesion regions in chest CT without the need for annotating the lesions for training. The easily-trained and high-performance deep learning algorithm provides a fast way to identify COVID-19 patients, which is beneficial to control the outbreak of SARS-CoV-2. The developed deep learning software is available at https://github.com/sydney0zq/covid-19-detection. [ABSTRACT FROM AUTHOR]

Ischemic stroke is characterized by permanent or transient obstruction of blood flow, which initiates a cascading pathological process, starting from acute ATP loss and ionic imbalance to subsequent membrane depolarization, glutamate excitotoxicity, and calcium overload. These initial events are followed by neuroinflammation and oxidative stress, eventually causing neuronal neurosis and apoptosis. Complicated interplays exist between these steps happening across various stages, which not only represent the complicated nature of ischemic pathology but also warrant a detailed delineation of the underlying molecular mechanisms to develop better therapeutic options. In the present study, we examined the neuroprotective effects of polydatin against ischemic brain injury using a rat model of permanent middle cerebral artery occlusion (MCAO). Our results demonstrated that polydatin treatment reduced the infarction volume and mitigated the neurobehavioral deficits, sequentially rescued neuronal apoptosis. Ischemic stroke induced an elevation of neuroinflammation and reactive oxygen species, which could be attenuated by polydatin via the reduced activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. In addition, polydatin upregulated the endogenous antioxidant nuclear factor erythroid 2-related factor 2, heme oxygenase-1, the thioredoxin pathway, and eventually reversed ischemic-stroke-induced elevation of ROS and inflammation in ischemic cortical tissue. The diverse and broad actions of polydatin suggested that it could be a multiple targeting neuroprotective agent in ameliorating the detrimental effects of MCAO, such as neuroinflammation, oxidative stress, and neuronal apoptosis. As repetitive clinical trials of neuroprotectants targeting a single step of stroke pathological process have failed previously, our results suggested that a neuroprotective strategy of acting at different stages may be more advantageous to intervene in the vicious cycles in MCAO. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effects of human parathyroid hormone (1-34) (PTH1-34; PTH) plus menaquinone-4 (vitamin K2; MK) on the osseous integration of hydroxyapatite (HA)-coated implants in osteoporotic rats. Ovariectomized female Sprague-Dawley rats were used for the study. Twelve weeks after bilateral ovariectomy, HA-coated titanium implants were inserted bilaterally in the femoral medullary canal of the remaining 40 ovariectomized rats. All animals were then randomly assigned to four groups: Control, MK, PTH and PTH + MK. The rats from groups MK, PTH and PTH + MK received vitamin K2 (30 mg/kg/day), PTH1-34 (60 μg/kg, three times a week), or both for 12 weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA and the bilateral femurs of rats were harvested for evaluation. The combination of PTH and MK clearly increased the serum levels of Gla-OC (a specific marker for bone formation) compared to PTH or MK alone. The results of our study indicated that all treated groups had increased new bone formation around the surface of implants and increased push-out force compared to Control. In addition, PTH + MK treatment showed the strongest effects in histological, micro-computed tomography and biomechanical tests. In summary, our results confirm that treatment with PTH1-34 and MK together may have a therapeutic advantage over PTH or MK monotherapy on bone healing around HA-coated implants in osteoporotic rats. [ABSTRACT FROM AUTHOR]

Reduced cerebral blood flow in Alzheimer's disease (AD) may occur in early AD, which contributes to the pathogenesis and/or pathological progression of AD. Reversing this deficit may have therapeutic potential. Certain traditional Chinese herbal medicines (e.g., Saponin and its major component Xueshuantong [XST]) increase blood flow in humans, but whether they could be effective in treating AD patients has not been tested. We found that systemic XST injection elevated cerebral blood flow in APP/PS1 transgenic mice using two-photon time-lapse imaging in the same microvessels before and after injection. Subchronic XST treatment led to improved spatial learning and memory and motor performance in the APP/PS1 mice, suggesting improved neural plasticity and functions. Two-photon time lapse imaging of the same plaques revealed a reduction in plaque size after XST treatment. In addition, western blots experiments showed that XST treatment led to reduced processing of amyloid-β protein precursor (AβPP) and enhanced clearance of amyloid-β (Aβ) without altering the total level of AβPP. We also found increased synapse density in the immediate vicinity of amyloid plaques, suggesting enhanced synaptic function. We conclude that targeting cerebral blood flow can be an effective strategy in treating AD. [ABSTRACT FROM AUTHOR]

Background: The reductions of perioperative blood loss and inflammatory response are important in total knee arthroplasty. Tranexamic acid reduced blood loss and the inflammatory response in several studies. However, the effect of epinephrine administration plus tranexamic acid has not been intensively investigated, to our knowledge. In this study, we evaluated whether the combined administration of low-dose epinephrine plus tranexamic acid reduced perioperative blood loss or inflammatory response further compared with tranexamic acid alone.Methods: This randomized placebo-controlled trial consisted of 179 consecutive patients who underwent primary total knee arthroplasty. Patients were randomized into 3 interventions: Group IV received intravenous low-dose epinephrine plus tranexamic acid, Group TP received topical diluted epinephrine plus tranexamic acid, and Group CT received tranexamic acid alone. The primary outcome was perioperative blood loss on postoperative day 1. Secondary outcomes included perioperative blood loss on postoperative day 3, coagulation and fibrinolysis parameters (measured by thromboelastography), inflammatory cytokine levels, transfusion values (rate and volume), thromboembolic complications, length of hospital stay, wound score, range of motion, and Hospital for Special Surgery (HSS) score.Results: The mean calculated total blood loss (and standard deviation) in Group IV was 348.1 ± 158.2 mL on postoperative day 1 and 458.0 ± 183.4 mL on postoperative day 3, which were significantly reduced (p < 0.05) compared with Group TP at 420.5 ± 188.4 mL on postoperative day 1 and 531.1 ± 231.4 mL on postoperative day 3 and Group CT at 520.4 ± 228.4 mL on postoperative day 1 and 633.7 ± 237.3 mL on postoperative day 3. Intravenous low-dose epinephrine exhibited a net anti-inflammatory activity in total knee arthroplasty and did not induce an obvious hypercoagulable status. Transfusion values were significantly reduced (p < 0.05) in Group IV, but no significant differences were observed in the incidence of thromboembolic complications, wound score, range of motion, and HSS score among the 3 groups (p > 0.05).Conclusions: The combined administration of low-dose epinephrine and tranexamic acid demonstrated an increased effect in reducing perioperative blood loss and the inflammatory response compared with tranexamic acid alone, with no apparent increased incidence of thromboembolic and other complications.Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Objectives. Several animal studies have demonstrated the positive effects of platelet-rich plasma (PRP) on disc degeneration retardation. The present meta-analysis was to verify the efficacy of PRP in retarding disc degeneration in animal. Methods. Relevant studies were identified and evaluated according to our inclusion and exclusion criteria. The standardized mean difference (SMD) and related 95% confidence interval (95% CI) were estimated to assess PRP efficiency. Results. In total, eleven studies were included in this meta-analysis. Significant differences were found in the PRP treatment group, which showed increased disc height (SMD = 2.66, 95% CI: 1.86, 3.47, p=0.000), increased MRI T2 signal intensity (SMD = −3.29, 95% CI: −4.44, −2.13, p=0.000), and decreased histological degeneration grade (SMD = −4.28, 95% CI: −5.26, −3.30, p=0.000). However, no significant increase in collagen II expression was found (SMD = 25389.74, 95% CI: −27585.72, 78365.21, p=0.348). Apart from the subgroup analysis of the disc height based on animal species (pig) and disc degeneration model (chymopapain induction), other subgroup analysis based on animal species (rabbit and rat), study design, disc degeneration model, and follow-up period demonstrated that PRP treatment can significantly restore disc height and increase MRI T2 signal intensity. Conclusions. PRP treatment is potentially effective in restoring disc height of rodent rabbit and rat, reducing histological degeneration grade, and increasing MRI T2 image signal. PRP injection may be promising therapy for retarding disc degeneration. [ABSTRACT FROM AUTHOR]

China is a country with a high tuberculosis (TB) burden. Spinal TB is one reason for the resurgence of TB in China. The objective of this study was to investigate the clinical and epidemiological features of patients with spinal TB in a teaching hospital of Southwest China. The study group comprised 967 patients with spinal TB who were admitted to the authors' institution from 1999 to 2013. Demographic characteristics, prevalence of symptoms and clinical manifestations, prevalence of multidrug resistance and extensive drug resistance of spinal TB, management and outcome, and incidence of complications were recorded and analyzed. The patients included 473 women and 494 men with a mean age of 35.86±15.68 years. The most common presentation of spinal TB was back pain, followed by night sweats and fever. The thoracic spine was the most commonly involved level, followed by the lumbar spine and cervical spine. The incidence of neurological involvement in spinal TB is 33.3%. Noncontiguous spinal TB was seen in 3.41% of cases. The incidence of concomitant pulmonary TB was 14.37%. A total of 740 patients were successfully treated with surgery and anti-TB drugs. No mortality was related to spinal TB. Spinal TB increased every year from 1999 to 2013 in Southwest China. Back pain is the most common clinical symptom, and the thoracic spine is the vertebral body most often involved. The most commonly used first- and second-line anti-TB drugs are isoniazid and levofloxacin, respectively. [Orthopedics.2016; 39(5):e838-e843.]. [ABSTRACT FROM AUTHOR]

Background: Degenerative cervical myelopathy (DCM) is an all-encompassing term that includes cervical spondylotic myelopathy (CSM), ossification of the posterior longitudinal ligament (OPLL), and other spinal abnormalities that cause cervical cord compression. It is unclear whether surgery is equally effective and safe for patients with OPLL as it is for those with other forms of DCM. The purpose of this study was to compare surgical outcomes of patients with OPLL and those with other forms of DCM.Methods: Four hundred and seventy-nine patients with symptomatic DCM were prospectively enrolled in the CSM-International study at sixteen sites. Patients' functional status was evaluated using the modified Japanese Orthopaedic Association scale (mJOA) and the Nurick score. Quality of life was assessed using patient-reported outcome measures, including the Neck Disability Index (NDI) and the Short Form (SF)-36. Postoperative functional and quality-of-life outcomes were assessed at two years of follow-up, and scores were compared between patients with and without OPLL.Results: Of 479 patients, 135 (28.2%) had radiographic evidence of OPLL, and 344 (71.8%) had other forms of DCM. The two groups did not differ significantly in demographics, surgical approach, or baseline myelopathy severity. Patients with OPLL achieved similar functional outcomes by two years following surgery compared with patients with other forms of DCM. With respect to quality of life, the NDI and most of the subscales of the SF-36 were not different between the two diagnostic groups. There was a higher risk of perioperative complications in the OPLL group (p = 0.054), although this relationship did not reach statistical significance. Rates of neurological complications did not differ significantly between diagnostic groups.Conclusions: Surgical decompression for the treatment of OPLL resulted in improvements in functional status and quality of life comparable to those seen in patients with other forms of DCM. Patients with OPLL were at a higher risk of perioperative complications than patients with other forms of DCM. [ABSTRACT FROM AUTHOR]

The effect of human parathyroid hormone 1-34 (PTH) and simvastatin (SIM) alone could promote bone healing in osteoporotic implant fixation, but there are no reports about the combined use of PTH and SIM for promotion of bone healing around implant in osteoporotic settings. This study aims to investigate effects of PTH + SIM on implant stabilization in osteopenic rats. Fourteen weeks after chronically fed a low protein diet, osteopenic rats randomly received implants. Subsequently, the animals were randomly divided into four groups: Control, SIM, PTH and PTH + SIM. Then all rats from groups PTH, SIM and PTH + SIM received PTH (40 μg/kg, three times a week), SIM (25 mg/kg, daily), or both for 12 weeks. The results of our study indicated that all treatments promoted bone healing around implant compared to Control, but PTH + SIM treatment showed significantly stronger effects than PTH or SIM alone in histological, micro-CT, and biomechanical tests. The results indicated additive effects of PTH and SIM on implant fixation in osteoporotic rats. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine (TCM) performs a good clinical practice and is showing a bright future in the treatment of diabetes mellitus (DM). TCM treatment has certain advantages of less toxicity and/or side effects, and herbs could provide multiple therapeutic effects. Berberine (BBR) is a classical natural medicine. In this review, we summarize the application of BBR in the treatment of DM from two aspects. First, modern pharmacological effects of BBR on glucose metabolism are summarized, such as improving insulin resistance, promoting insulin secretion, inhibiting gluconeogenesis in liver, stimulating glycolysis in peripheral tissue cells, modulating gut microbiota, reducing intestinal absorption of glucose, and regulating lipid metabolism. BBR is used to treat diabetic nephropathy (DPN), diabetic neuropathy (DN), and diabetic cardiomyopathy due to its antioxidant and anti-inflammatory activities. Second, the clinical application of BBR is reviewed, such as listing some clinical trials on the effectiveness and safety of BBR, explaining applicable stage and syndrome, the reasonable dose and dose formulation, and the toxicity and/or side effects. This review provides scientific evidence about BBR, as well as introducing some traditional Chinese medical theory and clinical experience, in order to guide clinician to use BBR more suitably and reasonably. [ABSTRACT FROM AUTHOR]

Background: To investigate the association between the single nucleotide polymorphism (SNP) of hypoxia-inducible factor1 α (HIF-1α) and the susceptibility to cervical spondylotic myelopathy (CSM) and its outcome after surgical treatment. Method: A total of 230 CSM patients and 284 healthy controls were recruited. All patients received anterior cervical corpectomy and fusion (ACF) and were followed for 12 months. The genotypes for two HIF-1α variants (1772C>T and 1790G>A) were determined. Results: In the present study, we found that the HIF-1α polymorphism at 1790G>A significantly affects the susceptibility to CSM and its clinical features, including severity and onset age. In addition, the 1790A>G polymorphism also determines the prognosis of CSM patients after ACF treatment. The GG genotype of 1790G>A polymorphism is associated with a higher risk to develop CSM, higher severity and earlier onset age. More importantly, we found that the 1790G>A polymorphism determines the clinical outcome in CSM patients who underwent ACF treatment. Conclusion: Our findings suggest that the HIF-1α 1790G>A polymorphism is associated with the susceptibility to CSM and can be used as predictor for the clinical outcome in CSM patients receiving ACF treatment. [ABSTRACT FROM AUTHOR]

Objectives: The mechanisms of ischemic stroke severity and early neurologic deterioration (END) are not fully understood. The aim of the present study was to investigate the association of six variants in MMP‐9 gene with ischemic stroke severity and the risk for END in ischemic stroke (IS) patients with atrial fibrillation (AF). Methods: This was a multi‐center, prospective, observational study of 615 acute IS patients with AF admitted to six participating hospitals between June 2016 and October 2017. Ischemic stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score on admission. END was defined as an increase of four or more points in NIHSS within 10 days of admission. Six variants of MMP‐9 gene were examined using mass spectrometry. Results: Among the 615 enrolled patients, 112 (18.2%) patients presented with moderate or severe stroke (NIHSS score ≥16), and 108 (17.6%) patients suffered from END within 10 days of admission. Multiple logistic analysis showed that prestroke antiplatelet therapy, prestroke anticoagulant therapy, rs3918242 CT/TT, and rs3787268 AG/GG were independent predictors for stroke severity. Cox proportional hazard regression revealed that diabetes mellitus, prestroke antiplatelet therapy, prestroke anticoagulant therapy, rs1056628 AC/CC, and rs3918242 CT/TT were independently associated with the risk of END. Conclusions: The incidence of moderate or severe stroke and END was very common in acute IS patients with AF. MMP‐9 polymorphisms were independently associated with severe stroke and higher risk of END, and prestroke antithrombotic treatment was associated with less severe stroke and lower risk of END in patients with AF. [ABSTRACT FROM AUTHOR]

Over the last several decades, both the academic and therapeutic fields have seen significant progress in the delivery of drugs to the inner ear due to recent delivery methods established for the systemic administration of drugs in inner ear treatment. Novel technologies such as nanoparticles and hydrogels are being investigated, in addition to the traditional treatment methods. Intracochlear devices, which utilize current developments in microsystems technology, are on the horizon of inner ear drug delivery methods and are designed to provide medicine directly into the inner ear. These devices are used for stem cell treatment, RNA interference, and the delivery of neurotrophic factors and steroids during cochlear implantation. An in-depth analysis of artificial neural networks (ANNs) in pharmaceutical research may be found in ANNs for Drug Delivery, Design, and Disposition. This prediction tool has a great deal of promise to assist researchers in more successfully designing, developing, and delivering successful medications because of its capacity to learn and self-correct in a very complicated environment. ANN achieved a high level of accuracy exceeding 0.90, along with a sensitivity of 95% and a specificity of 100%, in accurately distinguishing illness. Additionally, the ANN model provided nearly perfect measures of 0.99%. Nanoparticles exhibit potential as a viable therapeutic approach for bacterial infections that are challenging to manage, such as otitis media. The utilization of ANNs has the potential to enhance the effectiveness of nanoparticle therapy, particularly in the realm of automated identification of otitis media. Polymeric nanoparticles have demonstrated effectiveness in the treatment of prevalent bacterial infections in pediatric patients, suggesting significant potential for forthcoming therapeutic interventions. Finally, this study is based on a research of how inner ear diseases have been treated in the last ten years (2012–2022) using machine learning. • Cutting-edge analysis: Nanotech and AI revolutionize Inner Ear Disease treatment. • Optimizing drug delivery: Novel approaches for inner ear treatment. • Enhancing seismic behavior: Hybrid damping systems for braced frames. • Predictive tool: Artificial Neural Networks optimize damper distribution. • Promising outcomes: Metallic shear dampers and nanomaterials in inner ear therapy. [ABSTRACT FROM AUTHOR]

Background Context: Degenerative cervical myelopathy (DCM) is a progressive degenerative spine disease and the most common cause of spinal cord impairment in adults worldwide. Few studies have reported on regional variations in demographics, clinical presentation, disease causation, and surgical effectiveness.Purpose: The objective of this study was to evaluate differences in demographics, causative pathology, management strategies, surgical outcomes, length of hospital stay, and complications across four geographic regions.Study Design/setting: This is a multicenter international prospective cohort study.Patient Sample: This study includes a total of 757 symptomatic patients with DCM undergoing surgical decompression of the cervical spine.Outcome Measures: The outcome measures are the Neck Disability Index (NDI), the Short Form 36 version 2 (SF-36v2), the modified Japanese Orthopaedic Association (mJOA) scale, and the Nurick grade.Materials and Methods: The baseline characteristics, disease causation, surgical approaches, and outcomes at 12 and 24 months were compared among four regions: Europe, Asia Pacific, Latin America, and North America.Results: Patients from Europe and North America were, on average, older than those from Latin America and Asia Pacific (p=.0055). Patients from Latin America had a significantly longer duration of symptoms than those from the other three regions (p<.0001). The most frequent causes of myelopathy were spondylosis and disc herniation. Ossification of the posterior longitudinal ligament was most prevalent in Asia Pacific (35.33%) and in Europe (31.75%), and hypertrophy of the ligamentum flavum was most prevalent in Latin America (61.25%). Surgical approaches varied by region; the majority of cases in Europe (71.43%), Asia Pacific (60.67%), and North America (59.10%) were managed anteriorly, whereas the posterior approach was more common in Latin America (66.25%). At the 24-month follow-up, patients from North America and Asia Pacific exhibited greater improvements in mJOA and Nurick scores than those from Europe and Latin America. Patients from Asia Pacific and Latin America demonstrated the most improvement on the NDI and SF-36v2 PCS. The longest duration of hospital stay was in Asia Pacific (14.16 days), and the highest rate of complications (34.9%) was reported in Europe.Conclusions: Regional differences in demographics, causation, and surgical approaches are significant for patients with DCM. Despite these variations, surgical decompression for DCM appears effective in all regions. Observed differences in the extent of postoperative improvements among the regions should encourage the standardization of care across centers and the development of international guidelines for the management of DCM. [ABSTRACT FROM AUTHOR]

Background Context: It remains unclear whether cervical laminoplasty (LP) offers advantages over cervical laminectomy and fusion (LF) in patients undergoing posterior decompression for degenerative cervical myelopathy (DCM).Purpose: The objective of this study is to compare outcomes of LP and LF.Study Design/setting: This is a multicenter international prospective cohort study.Patient Sample: A total of 266 surgically treated symptomatic DCM patients undergoing cervical decompression using LP (N=100) or LF (N=166) were included.Outcome Measures: The outcome measures were the modified Japanese Orthopaedic Association score (mJOA), Nurick grade, Neck Disability Index (NDI), Short-Form 36v2 (SF36v2), length of hospital stay, length of stay in the intensive care unit, treatment complications, and reoperations.Methods: Differences in outcomes between the LP and LF groups were analyzed by analysis of variance and analysis of covariance. The dependent variable in all analyses was the change score between baseline and 24-month follow-up, and the independent variable was surgical procedure (LP or LF). In the analysis of covariance, outcomes were compared between cohorts while adjusting for gender, age, smoking, number of operative levels, duration of symptoms, geographic region, and baseline scores.Results: There were no differences in age, gender, smoking status, number of operated levels, and baseline Nurick, NDI, and SF36v2 scores between the LP and LF groups. Preoperative mJOA was lower in the LP compared with the LF group (11.52±2.77 and 12.30±2.85, respectively, p=.0297). Patients in both groups showed significant improvements in mJOA, Nurick grade, NDI, and SF36v2 physical and mental health component scores 24 months after surgery (p<.0001). At 24 months, mJOA scores improved by 3.49 (95% confidence interval [CI]: 2.84, 4.13) in the LP group compared with 2.39 (95% CI: 1.91, 2.86) in the LF group (p=.0069). Nurick grades improved by 1.57 (95% CI: 1.23, 1.90) in the LP group and 1.18 (95% CI: 0.92, 1.44) in the LF group (p=.0770). There were no differences between the groups with respect to NDI and SF36v2 outcomes. After adjustment for preoperative characteristics, surgical factors and geographic region, the differences in mJOA between surgical groups were no longer significant. The rate of treatment-related complications in the LF group was 28.31% compared with 21.00% in the LP group (p=.1079).Conclusions: Both LP and LF are effective at improving clinical disease severity, functional status, and quality of life in patients with DCM. In an unadjusted analysis, patients treated with LP achieved greater improvements on the mJOA at 24-month follow-up than those who received LF; however, these differences were insignificant following adjustment for relevant confounders. [ABSTRACT FROM AUTHOR]

Introduction: Several techniques have been described to treat tibial fractures, which respectively remains defects. This article presents a novel intra- and extramedullary fixation technique: percutaneous external fixator combined with titanium elastic nails (EF-TENs system). The purpose of this study is to introduce this new minimally invasive surgical technique and selective treatment of tibial fractures, particularly in segmental fractures, diaphysis fractures accompanied with distal or proximal bone subfissure, or fractures with poor soft-tissue problems.Methods: Following ethical approval, thirty-two patients with tibial fractures were treated by the EF-TENs system between January 2010 and December 2012. The follow-up studies included clinical and radiographic examinations. All relevant outcomes were recorded during follow-up.Results: All thirty-two patients were achieved follow-ups. According to the AO classification, 3 Type A, 9 Type B and 20 Type C fractures were included respectively. According to the Anderson-Gustilo classification, there were 5 Type Grade II, 3 Type Grade IIIA and 2 Type Grade IIIB. Among 32 patients, 8 of them were segmental fractures. 12 fractures accompanied with bone subfissure. Results showed no nonunion case, with an average time of 23.7 weeks (range, 14-32 weeks). Among them, there were 3/32 delayed union patients and 0/32 malunion case. 4/32 patients developed a pin track infection and no patient suffered deep infection. The external fixator was removed with a mean time of 16.7 weeks (range, 10-26 weeks). Moreover, only 1/32 patient suffered with the restricted ROM of ankle, none with the restricted ROM of knee.Conclusion: This preliminary study indicated that the EF-TENs system, as a novel intra- and extramedullary fixation technique, had substantial effects on selective treatment of tibial fractures. [ABSTRACT FROM AUTHOR]

The effect of human parathyroid hormone 1-34 (PTH) and simvastatin (SIM) alone could promote bone healing in osteoporotic osseous integration of the implant, but there are no reports about the combined use of PTH and SIM for promotion of bone healing around implant in osteoporotic settings still limited. This study aims to investigate effects of PTH+SIM on osseous integration of the implant in OVX rats. Female Sprague-Dawley rats were used for this study. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into four groups: group control; group SIM; group PTH and group PTH+SIM. Afterwards, all OVX rats received hydroxyapatite (HA)-coated titanium rods (external diameter and length are 1.5mm and 20mm) in the femoral medullary canal. Subsequently, the animals from group SIM, group PTH and group PTH+SIM received human parathyroid hormone 1-34 (60μg/kg, three times a week), SIM (5mg/kg daily), or both for 12 weeks. Implants were inserted bilaterally in all animals until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. All groups increased new bone formation around the surface of titanium rods and push-out force; group PTH+SIM showed the strongest effects on new bone formation and biomechanical strength. Additionally, these are significant difference observed in bone formation and push-out force between groups SIM and PTH. This finding suggests that intermittent administration of PTH or SIM alone has an effect to increase new bone formation on the surface of HA-coated implants in the osteoporotic condition, and the additive effects of combination PTH and SIM on osseous integration of the implant in OVX rats. [ABSTRACT FROM AUTHOR]

The multifactorial pathogenesis of Alzheimer’s disease (AD) implicates that multi-target-directed ligands (MTDLs) intervention may represent a promising therapy for AD. Amyloid-β (Aβ) aggregation and oxidative stress, two prominent neuropathological hallmarks in patients, play crucial roles in the neurotoxic cascade of this disease. In the present study, a series of novel (−)-meptazinol–melatonin hybrids were designed, synthesized and biologically characterized as potential MTDLs against AD. Among them, hybrids 7 – 7c displayed higher dual inhibitory potency toward cholinesterases (ChEs) and better oxygen radical absorbance capacity (ORAC) than the parental drugs. Furthermore, compound 7c could effectively inhibit Aβ self-aggregation, showed favorable safety and the blood–brain barrier (BBB) permeability. Therefore, 7c may serve as a valuable candidate that is worthy of further investigations in the treatment of AD. [ABSTRACT FROM AUTHOR]