Dendronized chitosan hydrogel with GIT1 to accelerate bone defect repair through increasing local neovascular amount.

Bone defects have long been a major healthcare issue because of the difficulties in regenerating bone mass volume and the high cost of treatment. G protein-coupled receptor kinase 2 interacting protein 1 (GIT1) has been proven to play an important role both in vascular development and in bone fracture healing. In this study, a type of thermoresponsive injectable hydrogel from oligoethylene glycol-based dendronized chitosan (G1-CS) was loaded with GIT1-plasmids (G1-CS/GIT1), and used to fill unicortical bone defects. RT-PCR analysis confirmed that G1-CS/GIT1 enhanced DNA transfection in MSCs both in vitro and in vivo. From the results of micro-CT, RT-PCR and histological analysis, it can be concluded that G1-CS/GIT1 accelerated the bone healing rate and increased the amount of neovascularization around the bone defects. In addition, an adeno-associated virus (AAV)-GIT1 was constructed to transfect mesenchymal stem cells. The results of capillary tube formation assay, immunofluorescence staining and western blot analysis proved that high expression of GIT1 induces mesenchymal stem cells to differentiate into endothelial cells. RT-PCR analysis and capillary tube formation assay confirmed that the Notch signaling pathway was activated in the differentiation process. Overall, we developed an efficient strategy through combination of injectable hydrogel and G1T1 for bone tissue engineering.

Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury.

Spinal cord injury (SCI) is a severe disease of the nervous system that causes irreparable damage and loss of function, for which no effective treatments are available to date. Engineered extracellular vesicles (EVs) carrying therapeutic molecules hold promise as an alternative SCI therapy depending on the specific functionalized EVs and the appropriate engineering strategy. In this study, we demonstrated the design of a drug delivery system of peptide CAQK-modified, siRNA-loaded EVs (C-EVs-siRNA) for SCI-targeted therapy. The peptide CAQK was anchored through a chemical modification to the membranes of EVs isolated from induced neural stem cells (iNSCs). CCL2-siRNA was then loaded into the EVs through electroporation. The modified EVs still maintained the basic properties of EVs and showed favorable targeting and therapeutic effects in vitro and in vivo. C-EVs-siRNA specifically delivered siRNA to the SCI region and was taken up by target cells. C-EVs-siRNA used the inherent anti-inflammatory and neuroreparative functions of iNSCs-derived EVs in synergy with the loaded siRNA, thus enhancing the therapeutic effect against SCI. The combination of targeted modified EVs and siRNA effectively regulated the microenvironmental disturbance after SCI, promoted the transformation of microglia/macrophages from M1 to M2 and limited the negative effects of the inflammatory response and neuronal injury on functional recovery in mice after SCI. Thus, engineered EVs are a potentially feasible and efficacious treatment for SCI, and may also be used to develop targeted treatments for other diseases.

Development and Clinical Trial of a New Orthopedic Surgical Robot for Positioning and Navigation.

Robot-assisted orthopedic surgery has great application prospects, and the accuracy of the robot is the key to its overall performance. The aim of this study was to develop a new orthopedic surgical robot to assist in spinal surgeries and to compare its feasibility and accuracy with the existing orthopedic robot. A new type of high-precision orthopedic surgical robot (Tuoshou) was developed. A multicenter, randomized controlled trial was carried out to compare the Tuoshou with the TiRobot (TINAVI Medical Technologies Co., Ltd., Beijing) to evaluate the accuracy and safety of their navigation and positioning. A total of 112 patients were randomized, and 108 patients completed the study. The position deviation of the Kirschner wire placement in the Tuoshou group was smaller than that in the TiRobot group (p = 0.014). The Tuoshou group was better than the TiRobot group in terms of the pedicle screw insertion accuracy (p = 0.016) and entry point deviation (p < 0.001). No differences were observed in endpoint deviation (p = 0.170), axial deviation (p = 0.170), sagittal deviation (p = 0.324), and spatial deviation (p = 0.299). There was no difference in security indicators. The new orthopedic surgical robot was highly accurate and optimized for clinical practice, making it suitable for clinical application.

Genetic Diversity and Population Structure of an Arctic Tertiary Relict Tree Endemic to China (Sassafras tzumu) Revealed by Novel Nuclear Microsatellite (nSSR) Markers.

Sassafras tzumu (Hemsl.) Hemsl., as an Arctic Tertiary relict woody species, is an ecologically and economically important deciduous tree endemic to southern China. Nonetheless, the genetic resources and backgrounds of S. tzumu are still lacking and remain largely unclear. Here, we predicted 16,215 candidate polymorphic nuclear microsatellite (nSSR) loci from the assembled nucleus databases of six geographic-distant individuals of S. tzumu via CandiSSR. Among these nSSRs, the di- (75.53%) and tri-nucleotide (19.75%) repeats were the most abundant, and 27 new polymorphic SSRs were developed and characterized in 136 individuals from six natural populations of S. tzumu. The majority of the above 27 SSRs (24 loci, 88.89%) presented moderate polymorphism (mean PIC = 0.356), and the transferability of these markers in other Sassafras species was high (85.19%). A moderately low level of genetic diversity and a high variation (FST = 0.286) of six wild populations of S. tzumu were illuminated by 16 selected polymorphic nSSRs, with the average expected heterozygosity (HE) of 0.430 at the species level and HE ranging from 0.195 to 0.387 at the population level. Meanwhile, a bottleneck effect was shown in two populations. Consistent with the results of the principal coordinate analysis (PCoA) and phylogenetic trees, structure analysis optimally divided these six S. tzumu populations into two clusters, and the further strong population subdivision appeared from K = 2 to K = 5, which corresponded to two evolutionarily significant units (ESUs). Moreover, the significant correlation between genetic and geographic distance was tested by the Mantel test (r = 0.742, p = 0.006), clarifying the effect about isolation by distance (IBD), which could be possibly explained by the low gene flow (Nm = 0.625), a relatively high degree of inbreeding (FIS = 0.166), a relatively large distribution, and mountainous barriers. Above all, our research not only enlarged the useful genetic resources for future studies of population genetics, molecular breeding, and germplasm management of S. tzumu and its siblings but also contributed to proposing scientific conservation strategies and schemes for the better preservation of S. tzumu and other Sassafras (Lauraceae) species.

A Cadaver Feasibility Study of Extradural Contralateral C7 Ventral Root Transfer Technique for Treating Upper Extremity Paralysis.

STUDY DESIGN: A total of 6 formalin-fixed cadavers were included in the cadaver feasibility study. OBJECTIVE: The aim was to ascertain the anatomical feasibility of extradural contralateral C7 ventral root transfer technique by cervical posterior. SUMMARY OF BACKGROUND DATA: Upper limb spastic hemiplegia is a common sequela after stroke. In our previous study, the authors established a method by transferring contralateral C7 dorsal and ventral roots to the corresponding C7 dorsal and ventral roots on the affected side in the cervical posterior. METHODS: In the present study, six formalin-fixed cadavers were dissected to confirm the anatomical feasibility. Experimental anastomosis in cadavers was conducted. The pertinent lengths of the extradural nerve roots were measured. The tissue structures surrounding regions between the extradural CC7 nerve roots and the vertebral artery were observed. The cervical magnetic resonance imaging scans of 60 adults were used to measure the distance between the donor and recipient nerves. RESULTS: Experimental anastomosis showed that the distance between the donor and recipient nerves was approximately 1 cm; the short segment of the sural nerve needed bridging. The distance between both exit sites of the exit of the extradural dura mater was 33.57±1.55 mm. The length of the extradural CC7 ventral root was 22.00±0.98 mm. The ventral distance (vd) and the dorsal distance (dd) in males were 23.98±1.72 mm and 30.85±2.22 mm ( P <0.05), while those in females were 23.28±1.51 mm and 30.03±2.16 mm, respectively. C7 vertebral transverse process, ligaments, and other soft tissues were observed between the vertebral artery and the extradural C7 nerve root. CONCLUSION: Under the premise of less trauma, our study shows that the extradural contralateral C7 ventral root transfer technique, in theory, yields better surgical results, including better recovery of motor function and complete preservation of sensory function. LEVEL OF EVIDENCE: 5.

Fatty acids derived from apoptotic chondrocytes fuel macrophages FAO through MSR1 for facilitating BMSCs osteogenic differentiation.

The nonunion following a fracture is associated with severe patient morbidity and economic consequences. Currently, accumulating studies are focusing on the importance of macrophages during fracture repair. However, details regarding the process by which macrophages facilitate endochondral ossification (EO) are largely unknown. In this study, we present evidence that apoptotic chondrocytes (ACs) are not inert corpses awaiting removal, but positively modulate the osteoinductive ability of macrophages. In vivo experiments revealed that fatty acid (FA) metabolic processes up-regulated following EO. In vitro studies further uncovered that FAs derived from ACs are taken up by macrophages mainly through macrophage scavenger receptor 1 (MSR1). Then, our functional experiments confirmed that these exogenous FAs subsequently activate peroxisome proliferator-activated receptor α (PPARα), which further facilitates lipid droplets generation and fatty acid oxidation (FAO). Mechanistically, elevated FAO is involved in up-regulating the osteoinductive effect by generating BMP7 and NAD+/SIRT1/EZH2 axis epigenetically controls BMP7 expression in macrophages cultured with ACs culture medium. Our findings advanced the concept that ACs could promote bone regeneration by regulating metabolic and function reprogram in macrophages and identified macrophage MSR1 represents a valuable target for fracture treatments.

A comparison of robot-assisted and fluoroscopy-assisted kyphoplasty in the treatment of multi-segmental osteoporotic vertebral compression fractures.

Osteoporotic vertebral compression fracture (OVCF) has become a major public health issue that becomes more pressing with increasing global aging. Percutaneous kyphoplasty (PKP) is an effective treatment for OVCF. Robot-assisted PKP has been utilized in recent years to improve accuracy and reduce complications. However, the effectiveness of robot-assisted PKP in the treatment of multi-segmental OVCF has yet to be proved. This study was designed to compare the efficacy of robot-assisted and conventional fluoroscopy-assisted multi-segmental PKP. A total of 30 cases with multi-segmental OVCF between April 2019 and April 2021 were included in this study. Fifteen cases were assigned to the robot-assisted PKP group (robot group) and 15 cases to the conventional fluoroscopy-assisted PKP group (conventional fluoroscopy group). The number of fluoroscopic exposures, fluoroscopic dose, operation time, cement leakage rate, visual analog scale (VAS) score, vertebral kyphosis angle (VKA), and height of fractured vertebral body (HFV) were compared between the 2 groups. The number of fluoroscopic exposures, fluoroscopic doses, and cement leakage rates in the robot group were lower than in the conventional fluoroscopy group ( P<0.05) while the operative time in the robot group was longer than in the conventional fluoroscopy group ( P<0.05). VAS score and VKA were decreased and HFV was increased after surgery in both groups ( P<0.05). Therefore, robot-assisted PKP for the treatment of multi-segmental OVCF can reduce the number of fluoroscopic exposures, fluoroscopic doses, and cement leakage compared to conventional treatment. As such, robot-assisted PKP has good application prospects and is potentially more effective in the treatment of multi-segmental OVCF.

Effectiveness of Tirobot-assisted vertebroplasty in treating thoracolumbar osteoporotic compression fracture.

BACKGROUND: Percutaneous kyphoplasty is the main method in the treatment of thoracolumbar osteoporotic compression fractures. However, much radiation exposure during the operation harms the health of surgeons and patients. In addition, the accuracy of this surgery still needs to be improved. This study aimed to assess the radiation exposure and clinical efficacy of Tirobot-assisted vertebroplasty in treating thoracolumbar osteoporotic compression fracture. METHODS: Included in this retrospective cohort study were 60 patients (60-90 years) who had undergone unilateral vertebroplasty for thoracolumbar osteoporotic compression fracture at our hospital between June 2019 and June 2020. All showed no systemic diseases and were assigned to Tirobot group (treated with Tirobot-assisted approach) and control group (treated with traditional approach). Fluoroscopic frequency, operative duration, length of stay (LOS), post-operative complications (cement leakage, infection, and thrombosis), and pre-operative and pre-discharge indexes (VAS score, JOA score, and Cobb's angle) were compared. RESULTS: The fluoroscopic frequency (P < 0.001) and post-operative complications (P = 0.035) in Tirobot group were significantly lower than those in control group. The operative duration and LOS in the Tirobot group were shorter than those in the control group, but the differences were not statistically significant (P = 0.183). Pre-discharge VAS score and Cobb's angle decreased, and JOA increased after surgeries in both groups. These three indexes showed a significant difference after surgery in each group (P < 0.001), but not between groups (PVAS = 0.175, PCobb's = 0.585, PJOA = 0.448). CONCLUSION: The Tirobot-assisted vertebroplasty can reduce surgery-related trauma, post-operative complications, and patients' and operators' exposure to radiation. As a safe and effective strategy, this surgery can realize the quick recovery from thoracolumbar osteoporotic compression fracture.

Population Pharmacokinetics of Caspofungin and Dosing Optimization in Children With Allogeneic Hematopoietic Stem Cell Transplantation.

Caspofungin is the first echinocandin antifungal agent that licented for pediatric use in invasive candidiasis and aspergillosis. In this study, we evaluated the population pharmacokinetics of caspofungin and investigate appropriate dosing optimization against Candida spp. in children with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in order to improve therapeutic efficacy. All participants received a recommended caspofungin 70 mg/m2 loading dose followed by 50 mg/m2 maintenance dose. A one-compartment model with first-order elimination was best fitted the data from 48 pediatric patients. Body surface area and aspartate aminotransferase had significant influence on caspofungin clearance from covariate analysis. Our results reviewed that dose adjustment is not necessary in patients with mild liver dysfunction. Monte Carlo simulations were performed using pharmacokinetic data from our study to evaluate the probability of target attainment (PTA) of caspofungin regimen in terms of AUC24/MIC targets against Candida spp. The results of simulations predicted that a caspofungin 70 mg/m2 at first dose, 50 mg/m2 of daily dose may have a high probability of successful outcome against C. albicans and C. glabrata whilst 60 mg/m2 maintenance dose was required for fungistatic target against C. parapsilosis but may be not sufficient to achieve optimal fungicidal activity. Caspofungin standard regimen had high probability of successful outcome against C. albicans (MIC ⩽ 0.25 mg/L) and C. glabrata (MIC ⩽ 0.5 mg/L) but insufficient for C. parapsilosis with MIC > 0.25 mg/L. That may provide an evidence based support to caspofungin individualized administration and decrease the risk of therapeutic failure in allo-HSCT pediatric patients.

Spontaneous Cervical Intradural Disc Herniation Presenting withBrown-Sequard Syndrome at C6-C7 level.

INTRODUCTION: Intradural disc herniation is a rare disease and it accounts for 0.26-0.30% of all herniated discs. Little was known about intradural disc herniation in the previous studies. CASE REPORT: Here, we report a 49-year-old male patient with Brown-Sequard syndrome caused by spontaneous cervical intradural disc herniation at C6-C7 level. CONCLUSIONS: It is difficult to be diagnosed before the surgery through computed tomography scans, myelograms, and magnetic resonance image scans. Once it was diagnosed, an operation should be performed.

Neural stem cell small extracellular vesicle-based delivery of 14-3-3t reduces apoptosis and neuroinflammation following traumatic spinal cord injury by enhancing autophagy by targeting Beclin-1.

Neural stem cell-derived small extracellular vesicles (NSC-sEVs) play an important role in the repair of tissue damage. Our previous in vitro and in vivo studies found that preconditioning with NSC-sEVs promoted the recovery of functional behaviors following spinal cord injury by activating autophagy. However, the underlying mechanisms for such observations remain unclear. In this study, we further explored the mechanisms by which NSC-sEVs repair spinal cord injury via autophagy. We found that NSC-sEVs contain 14-3-3t protein, of which the overexpression or knockdown enhanced and decreased autophagy, respectively. In addition, 14-3-3t overexpression enhanced the anti-apoptotic and anti-inflammatory effects of NSC-sEVs, further promoting functional behavior recovery following spinal cord injury. The overexpression of 14-3-3t was used to further validate the in vivo results through a series of in vitro experiments. Conversely, knockdown of 14-3-3t attenuated the anti-apoptotic and anti-inflammatory effects of NSC-sEVs. Further studies also confirmed that NSC-sEVs increased Beclin-1 expression, with which 14-3-3t interacted and promoted its localization to autophagosome precursors. In this study, we found that NSC-sEVs deliver 14-3-3t, which interacts with Beclin-1 to activate autophagy. Our results indicate that 14-3-3t acts via a newly-discovered mechanism for the activation of autophagy by NSC-sEVs.

Effect of zoledronic acid on lumbar spinal fusion in osteoporotic patients.

PURPOSE: To investigate the effect of zoledronic acid (ZA) on lumbar spinal fusion in patients with osteoporosis. METHODS: This retrospective study includes 94 osteoporotic patients suffering from lumbar degenerative diseases or lumbar fracture who underwent lumbar spinal fusion in our institution from January 2013 to August 2014. They were divided into ZA group and control group according to whether the patient received ZA infusion or not. The patients in ZA group were given 5 mg intravenous ZA at the 3rd-5th days after operation. All patients took daily oral supplement of 600 mg calcium carbonate and 800 IU vitamin D during the follow-up after operation. The Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), and Short Form 36 (SF-36) scores were recorded preoperatively and post-operatively to evaluate the clinic outcomes; the spinal fusion was assessed by X-ray or CT Scan. RESULTS: 64 patients finished the final follow-up, including 30 patients in ZA group and 34 patients in control group. No significant difference was observed in gender, age, and preoperative BMI VAS, ODI, and SF-36 scores between the two groups (P > 0.05). The post-operative VAS and ODI scores decreased rapidly at 3 and 6 months, but rose back slightly at 12 and 24 months in both groups. On the contrary, post-operative SF-36 scores increased rapidly at 3 and 6 months, while fell back slightly at 12 and 24 months, with a statistically significant difference between the two groups at 12 months, but not at 3 and 6 month post-operation. The spinal fusion rate in ZA group was 90% at 6 months, 92% at 12 months, while it was 75% at 6 months, 92.86% at 12 months in control group, significantly different between the two groups at 12 months, but not at 6 months. In the whole follow-up period, adjacent vertebral compressing fracture occurred in five patients in control group, none in ZA group. No pedicle screw loosening was observed in ZA group, with six in control group. CONCLUSIONS: Zoledronic acid accelerates spinal fusion, shortens the time of fusion without changing fusion rate, and also decreases the risk of adjacent vertebral compressing fracture and the rate of pedicle screw loosening, resulting in the improvement of clinical outcomes and quality of life.

Surgical trauma and low-dose methylprednisolone modulate the severity of the acute-phase response induced by zoledronic acid infusion.

The aim of the present study was to investigate risk factors for the development of an acute-phase response (APR) associated with the initial zoledronic acid (ZA) infusion in patients undergoing surgery, and to assess whether its onset may be reduced by post-dose administration of low-dose methylprednisolone (MP) or acetaminophen. A retrospective study of patients with osteoporosis who attended the departments of orthopedics and endocrinology of a single hospital and received 5 mg ZA was conducted; the patients included surgical and non-surgical cases. A total of 450 ZA-naïve patients who were treated with acetaminophen following ZA infusion were stratified based on whether they suffered APR (APR+) or not (APR-). In addition, 155 of the aforementioned acetaminophen-treated patients (acetaminophen group) were compared with another 32 patients from the orthopedic department who were treated with MP immediately following ZA infusion (MP group). Inflammatory marker levels were significantly higher in APR+ patients than in APR- patients, and the odds ratios of experiencing APR following minimally invasive or open surgery were found to be 3.54 (P<0.001) and 5.71 (P<0.001), respectively, compared with non-surgical intervention after multiple adjustments. C-reactive protein levels prior to dosing were positively correlated with body temperature (r=0.023; P<0.001). The severity of APR also exhibited a negative correlation with 23-hydroxyvitamin D3 levels (r=-0.006; P<0.05). Patients treated with MP following surgery and ZA infusion had a significantly lower incidence of APR compared with those treated with acetaminophen (6.3 vs. 62.6%; P<0.05). However, no significant differences were observed in bone mineral density between the MP and acetaminophen groups at 12 months post-surgery. The results of the present study suggest that surgical trauma serves a key role in ZA-associated APR, and low-dose MP may a suitable post-dose treatment to manage the symptoms of APR in patients undergoing surgery.

Endogenous Parathyroid Hormone Promotes Fracture Healing by Increasing Expression of BMPR2 through cAMP/PKA/CREB Pathway in Mice.

BACKGROUND/AIMS: Endogenous parathyroid hormone (PTH) plays an important role in fracture healing. This study investigated whether endogenous PTH regulates fracture healing by bone morphogenetic protein (BMP) and/or the transforming growth factor-ß (TGF-ß) signaling pathway. METHODS: Eight-week-old wild-type (WT) and PTH-knockout (PTH KO) male mice were selected, and models of open right-femoral fracture were constructed. Fracture healing and callus characteristics of mice in the two groups were compared by X-ray, micro-computed tomography, histological, and immunohistochemical examinations. Bone marrow mesenchymal stem cells (BMMSCs) of 8-week-old WT and PTHKO male mice were obtained and induced into osteoblasts and chondrocytes. RESULTS: We found that expression levels of Runt-related transcription factor (RUNX2), bone morphogenetic protein-receptor-type Ⅱ (BMPR2), phosphorylated Smad 1/5/8, and phosphorylated cyclic adenosine monophosphate-responsive element binding protein (CREB) in the callus of PTHKO mice were significantly decreased, whereas no significant difference in expression of SOX9, TGF-ßR2,or pSMAD2/3 was observed between PTHKO and WT mice. Additionally, the activity of osteoblast alkaline phosphatase was low at 7 days post-induction, and was upregulated by addition of PTH or dibutyryl cyclic adenosine monophosphate (dbcAMP) to the cell culture. Furthermore, H89 (protein kinase A inhibitor)eliminated the simulating effects of PTH and dbcAMP, and a low concentration of cyclic adenosine monophosphate (cAMP) was observed in PTHKO mouse BMMSCs. CONCLUSION: These results suggested that endogenous PTH enhanced BMPR2 expression by a cAMP/PKA/CREB pathway in osteoblasts, and increased RUNX2 expression through transduction of the BMP/pSMAD1/5/8 signaling pathway.

Correlation Analysis Between Modic Change of Cervical Vertebrae and Intramedullary High Signal Intensity.

PURPOSE: Clinical studies have shown that endplate Modic change in the cervical spine and intramedullary high signal intensity often occurs simultaneously. We aimed to investigate whether there is a correlation between Modic change and intramedullary high signal intensity, and to explore the possible risk factors. MATERIALS AND METHODS: In total, 133 patients with cervical spondylotic myelopathy treated at the First Affiliated Hospital of Nanjing Medical University between May 2009 and March 2013 were enrolled in the study. Preoperative cervical magnetic resonance imaging and radiographs in hyperextension and hyperflexion were analyzed. With regard to magnetic resonance imaging, all patients were classified into groups according to Modic change types and intramedullary high signal intensity; the ratio of spinal cord compression reflected the degree of spinal stenosis. For plain radiographs, total range of motion (ROM) and segmental ROM of the cervical vertebrae were measured. RESULTS: Modic change of the cervical vertebral endplate and intramedullary high signal intensity demonstrated a significantly positive correlation. In patients with Modic change and intramedullary high signal intensity, the segmental angle of motion of the cervical vertebrae in hyperextension, cervical segmental ROM, and ratio of spinal cord compression were significantly higher than in patients without Modic change and intramedullary high signal intensity. CONCLUSIONS: The occurrence of Modic change and intramedullary high signal intensity are related to cervical instability and spinal canal stenosis. Severe disc protrusion may cause an increase of ROM in cervical hyperextension. Such patients are more prone to Modic change of the cervical vertebral endplate and intramedullary high signal intensity.

The complete mitochondrial genome of Paramesotriton chinensis (Caudata: Salamandridae) and phylogenetic studies of Paramesotriton.

The complete mitochondrial genome of the Asian warty newt Paramesotriton chinensis was sequenced. The complete mitogenome of P. chinensis is a circular double-stranded DNA sequence that is 16,361 bp long and was biased toward A + T content at 61.3% (33.0% A, 28.3% T, 23.9% C, and 14.7% G). The complete mitogenome of P. chinensis consists of 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), 1 ribosomal RNAs (16S rRNA), and 1 putative control region. This study presented the complete mitogenome of P. chinensis and provided essential and important DNA molecular data for further phylogenetic and evolutionary analysis for genus Paramesotriton.

Desipramine improves depression-like behavior and working memory by up-regulating p-CREB in Alzheimer's disease associated mice.

Aggregation of amyloid [Formula: see text] protein (A[Formula: see text] and progressive loss of memory are the main characteristics of Alzheimer's disease (AD). It is noteworthy that approximately 40% of AD patients have depressive symptom. The close correlation between cognitive deficits and mental depression suggests a possibility that antidepression treatment might be beneficial to cognitive improvement in AD. The present study, by using tail-suspension test (TST), forced swimming, alternative electro-stimulus Y maze test and immunohistochemistry, examined the neuroprotective effects of desipramine, a newer generation tricyclic antidepressants (TCA), and investigated its possible molecular mechanism. The results showed that: (1) intra-hippocampal injection of A[Formula: see text] induced depression-like behavior and associative learning deficits in mice, with an increased mean immobility time in tail-suspension and forced swimming test and an increased mean error times in Y maze test; (2) after treatment with desipramine (10[Formula: see text]mg/kg, i.p.), the average immobility time significantly decreased, from [Formula: see text][Formula: see text]s in A[Formula: see text] group to [Formula: see text][Formula: see text]s in A[Formula: see text] plus desipramine group ([Formula: see text]) in TST and from [Formula: see text][Formula: see text]s to [Formula: see text][Formula: see text]s ([Formula: see text] or 9, [Formula: see text]) in forced swimming test, respectively;the mean error times of mice in Y maze test also significantly decreased, from [Formula: see text] in A[Formula: see text] group to [Formula: see text] in A[Formula: see text] plus desipramine group ([Formula: see text], [Formula: see text]); (3) desipramine administration significantly prevented against A[Formula: see text]-induced down-regulation of phosphorylated cAMP response element binding protein (p-CREB) in the hippocampus. These results indicate that A[Formula: see text] could concurrently mimic the depression-like behavior and working memory disorder in mice, while desipramine could effectively reverse both the deficits induced by A[Formula: see text]. The neuroprotection of desipramine may be involved in the up-regulation of p-CREB level in the hippocampus of mice.

Evaluation of surgical outcome of Jack vertebral dilator kyphoplasty for osteoporotic vertebral compression fracture-clinical experience of 218 cases.

BACKGROUND: Osteoporotic vertebral compression fracture is a serious complication of osteoporosis. Various vertebral kyphoplasty surgeries, which have their own unique features, are commonly used for osteoporotic vertebral compression fracture. Based on the anatomic property of the thoracolumbar vertebral pedicle that its horizontal diameter is twice that of the vertical diameter, we designed Jack vertebral dilator for better restoration of the vertebral height by manipulating the mechanical force. METHODS: A total of 218 patients (236 vertebrae) with osteoporotic vertebral compression fracture were treated with Jack vertebral dilator. Surgery was successfully completed in all cases, and all the 218 patients were followed up for an average of 14.2 months (range 3 to 30 months). RESULTS: Bone cement leakage occurred in 12 cases, but no symptoms were reported. No other complications were noticed. The VAS scores were 8.2 ± 1.3, 1.7 ± 0.9, and 1.8 ± 0.8 and the ODI was 78.2 ± 13.3 %, 18.5 ± 7.3 %, and 20.9 ± 6.8 % before surgery and 1 week after surgery and at the final follow-up, respectively. The anterior vertebral body height was 19.3 ± 3.2, 25.1 ± 2.6, and 24.9 ± 2.6 mm and the central vertebral body height was 18.7 ± 3.0, 24.8 ± 3.0, and 24.5 ± 2.9 mm before surgery and 1 week after surgery and at the final follow-up, respectively. Cobb angle was 16.2° ± 6.6°, 8.1° ± 5.6°, and 8.5° ± 5.6° before surgery and 1 week after surgery and at the final follow-up, respectively. CONCLUSIONS: Jack vertebral dilator kyphoplasty for osteoporotic vertebral compression fracture is safe, feasible, and effective and has the prospect of further broad application in the future.

An MRI-based feasibility study of unilateral percutaneous vertebroplasty.

BACKGROUND: Percutaneous vertebroplasty (PVP) has been demonstrated to be effective in the treatment of osteoporotic fracture. The bilateral pedicular approach is the most frequently used method. However, unilateral PVP is becoming increasingly more attractive for surgeons because of its numerous benefits, including lower radiation exposure, less tissue injury, and less bone cement leakage. The purpose of this study was to investigate the anatomical feasibility of unilateral PVP by exploring the differences in the puncture success rate of the unilateral pedicular approach among different lumbar segments, between men and women, and between the left and right sides. METHODS: Punctures were simulated on magnetic resonance imaging scans of 200 patients (100 men, 100 women) at a maximum angle via a pedicular approach. The distance between the entry point and the midline of the vertebral body, the maximum puncture angle, the puncture success value, and the puncture success rate were measured and compared among different lumbar levels, between the two sexes, and between the left and right sides. RESULTS: The maximum puncture distance between the entry point and the midline gradually increased from L1 to L5, and the maximum puncture angle showed the same tendency from L1 to L5. The puncture success values for L3 and L4 were higher than those for the other lumbar levels (L1, 31.53 ± 34.45; L2, 42.15 ± 28.06; L3, 56.21 ± 18.30; L4, 56.20 ± 12.93; and L5, 48.01 ± 6.88). The puncture success rates varied from 69.5 to 98.0 % among the different lumbar levels; L3 and L4 were the two highest (L3, 95.5 %; L4, 98.0 %). There were significant differences in these measurements between men and women and between the left and right sides. CONCLUSIONS: PVP with the unilateral puncture approach appears more likely to succeed at L3 to L5 than at L1 and L2. The unilateral approach might be more suitable for men than women at levels other than L5. Additionally, the left pedicular approach might be optimal for unilateral PVP procedures.

Surgical outcomes of mini-open Wiltse approach and conventional open approach in patients with single-segment thoracolumbar fractures without neurologic injury.

This study aimed to introduce a novel mini-open pedicle screw fixation technique via Wiltse approach, and compared it with the traditional posterior open method. A total of 72 cases of single-segment thoracolumbar fractures without neurologic injury underwent pedicle screw fixation via two different approaches. Among them, 37 patients were treated using posterior open surgery, and 35 patients received mini-open operation via Wiltse approach. Crew placement accuracy rate, operative time, blood loss, postoperative drainage, postoperative hospitalization time, radiation exposure time, postoperative improvement in R value, Cobb's angle and visual analog scale (VAS) scores of the two methods were compared. There were no significant differences in the accuracy rate of pedicle screw placement, radiation exposure and postoperative R value and Cobb's angle improvement between the two groups. However, the mini-open method had obvious advantages over the conventional open method in operative time, blood loss, postoperative drainage, postoperative hospitalization time, and postoperative improvement in VAS. The mini-open pedicle screw technique could be applied in treatment of single-segment thoracolumbar fracture without neurologic injury and had advantages of less tissue trauma, short operative and rehabilitative time on the premise of guaranteed accuracy rate and no increased radiation exposure.