Protectin D1 ameliorates non-compressive lumbar disc herniation through SIRT1-mediated CGRP signaling.

Background. Neuro-inflammatory response promotes the initiation and sustenance of lumbar disc herniation (LDH). Protectin D1 (PD1), as a new type of specialized pro-resolving mediator (SPM), can improve the prognosis of various inflammatory diseases. Recent studies have shown that over representation of calcitonin gene-related peptides (CGRP) may activate nociceptive signaling following nerve injury. Silent information regulator 1 (SIRT1) is ubiquitously expressed in the dorsal horn of the spinal cord and plays a role in the pathogenesis of LDH. In this study, we investigated the analgesic effects of PD1 and elucidated the impact of neurogenic inflammation in the pathogenesis of neuropathic pain induced by non-compressive lumbar disc herniation (NCLDH) in a rat model. Methods. NCLDH models were established by applying protruding autologous nucleus pulposus to the L5 Dorsal root ganglion (DRG). PD1, SIRT1 antagonist or agonist, CGRP or antagonist were administered as daily intrathecal injections for three consecutive days postoperatively. Behavioral tests were conducted to assess mechanical and thermal hyperalgesia. The ipsilateral lumbar (L4-6) segment of the spinal dorsal horn was isolated for further analysis. Alterations in the release of SIRT1 and CGRP were explored using western blot and immunofluorescence. Results. Application of protruded nucleus (NP) materials to the DRG induced mechanical and thermal allodynia symptoms, and deregulated the expression of pro-inflammatory and anti-inflammatory cytokines in rats. Intrathecal delivery of PD1 significantly reversed the NCLDH-induced imbalance in neuro-inflammatory response and alleviated the symptoms of mechanical and thermal hyperalgesia. In addition, NP application to the DGRs resulted the spinal upregulation of CGRP and SIRT1 expression, which was almost restored by intrathecal injection of PD1 in a dose-dependent manner. SIRT1 antagonist or agonist and CGRP or antagonist treatment further confirmed the result. Conclusion. Our findings indicate PD1 has a potent analgesic effect, and can modulate neuro-inflammation by regulating SIRT1-mediated CGRP signaling in NCLDH.

Simple Scalable Multimodal Semantic Segmentation Model.

Visual perception is a crucial component of autonomous driving systems. Traditional approaches for autonomous driving visual perception often rely on single-modal methods, and semantic segmentation tasks are accomplished by inputting RGB images. However, for semantic segmentation tasks in autonomous driving visual perception, a more effective strategy involves leveraging multiple modalities, which is because different sensors of the autonomous driving system bring diverse information, and the complementary features among different modalities enhance the robustness of the semantic segmentation modal. Contrary to the intuitive belief that more modalities lead to better accuracy, our research reveals that adding modalities to traditional semantic segmentation models can sometimes decrease precision. Inspired by the residual thinking concept, we propose a multimodal visual perception model which is capable of maintaining or even improving accuracy with the addition of any modality. Our approach is straightforward, using RGB as the main branch and employing the same feature extraction backbone for other modal branches. The modals score module (MSM) evaluates channel and spatial scores of all modality features, measuring their importance for overall semantic segmentation. Subsequently, the modal branches provide additional features to the RGB main branch through the features complementary module (FCM). Leveraging the residual thinking concept further enhances the feature extraction capabilities of all the branches. Through extensive experiments, we derived several conclusions. The integration of certain modalities into traditional semantic segmentation models tends to result in a decline in segmentation accuracy. In contrast, our proposed simple and scalable multimodal model demonstrates the ability to maintain segmentation precision when accommodating any additional modality. Moreover, our approach surpasses some state-of-the-art multimodal semantic segmentation models. Additionally, we conducted ablation experiments on the proposed model, confirming that the application of the proposed MSM, FCM, and the incorporation of residual thinking contribute significantly to the enhancement of the model.

Multi-Camera-Based Universal Measurement Method for 6-DOF of Rigid Bodies in World Coordinate System.

The measurement of six-degrees-of-freedom (6-DOF) of rigid bodies plays an important role in many industries, but it often requires the use of professional instruments and software, or has limitations on the shape of measured objects. In this paper, a 6-DOF measurement method based on multi-camera is proposed, which is accomplished using at least two ordinary cameras and is made available for most morphological rigid bodies. First, multi-camera calibration based on Zhang Zhengyou's calibration method is introduced. In addition to the intrinsic and extrinsic parameters of cameras, the pose relationship between the camera coordinate system and the world coordinate system can also be obtained. Secondly, the 6-DOF calculation model of proposed method is gradually analyzed by the matrix analysis method. With the help of control points arranged on the rigid body, the 6-DOF of the rigid body can be calculated by the least square method. Finally, the Phantom 3D high-speed photogrammetry system (P3HPS) with an accuracy of 0.1 mm/m was used to evaluate this method. The experiment results show that the average error of the rotational degrees of freedom (DOF) measurement is less than 1.1 deg, and the average error of the movement DOF measurement is less than 0.007 m. In conclusion, the accuracy of the proposed method meets the requirements.

Inhibition of MicroRNA-9 Improves Fracture Healing by Modulating the Bone Morphogenetic Protein-7 Pathway.

We evaluated the effect of microRNA (miR)-9 inhibition on fracture healing in a rat model of femoral fracture. The rats were divided into sham, negative control and miR-9 inhibitor groups. The miR-9 inhibitor group received 30 pmol/mL inhibitor intrathecally for 8 consecutive weeks following surgery-induced femoral fracture. The effect of miR-9 inhibition on fracture healing was estimated by determining the bone mineral density (BMD) and by performing X-ray analysis of the fractured bone. The serum levels of markers of bone formation were estimated by enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction, and western blotting and immunohistochemical analysis were performed to assess the effect of miR-9 inhibition on fracture healing. The BMD at the fracture site was significantly higher in the miR-9 inhibitor group than in the negative control group. Inhibition of miR-9 blocked the fracture gap and resulted in new callus formation at the fracture site. The serum levels of osteocalcin and bone GLA protein were increased and that of alkaline phosphatase was decreased by inhibition of miR-9 compared to levels in the negative control. However, inhibition of miR-9 significantly increased the mRNA levels of runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 7 (BMP-7) in the bone tissue at the fracture site compared to the negative control group; this result was confirmed by western blotting. In conclusion, -miR-9 inhibition enhanced fracture healing by modulating the BMP-7/Runx2 signalling pathway in a rat model of femoral fracture.

Serine/Threonine Kinase 35, a Target Gene of STAT3, Regulates the Proliferation and Apoptosis of Osteosarcoma Cells.

BACKGROUND/AIMS: Serine/threonine kinase 35 (STK35) may be associated with Parkinson disease and human colorectal cancer, but there have been no reports on the expression levels or roles of STK35 in osteosarcoma. METHODS: STK35 mRNA expression was determined in osteosarcoma and bone cyst tissues by real-time PCR. Cell proliferation and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis, respectively. RESULTS: STK35 was up-regulated in osteosarcoma tissues as indicated by analyzing publicly available expression data (GEO dataset E-MEXP-3628) and real-time PCR analysis on our own cohort. We subsequently investigated the effects of STK35 knockdown on two osteosarcoma cell lines, MG63 and U2OS. STK35 knockdown inhibited the growth of osteosarcoma cells in vitro and in xenograft tumors. Meanwhile, STK35 knockdown enhanced apoptosis. Expression of the active forms and the activity of two major executioner caspases, caspase 3 and caspase 7, were also increased in osteosarcoma cells with STK35 silenced. Additionally, Gene Set Enrichment Analysis (GSEA) identified that the JAK/STAT signaling pathway was positively correlated with STK35 expression. The mRNA expression of STK35 was repressed by STAT3 small interfering RNA (siRNA), but not by siRNA of STAT4, STAT5A or STAT6. A luciferase reporter assay further demonstrated that STAT3 transcriptionally regulated STK35 expression. A chromatin immunoprecipitation (ChIP) assay confirmed the direct recruitment of STAT3 to the STK35 promoter. The promotion effects of STAT3 knockdown on cell apoptosis were partially abolished by STK35 overexpression. Furthermore, STK35 mRNA expression was positively correlated with STAT3 mRNA expression in osteosarcoma tissues by Pearson correlation analysis. CONCLUSIONS: These results collectively reveal that STAT3 regulates the transcription of STK35 in osteosarcoma. STK35 may exert an oncogenic role in osteosarcoma.

Safety and Efficacy of Tranexamic Acid in Total Knee Arthroplasty.

BACKGROUND: The prevalence of total knee arthroplasty (TKA) is increasing, which is one of the most frequent operations in orthopedic practice. To further investigate the safe and effective role of using tranexamic acid (TA) in reducing transfusion rate and blood loss in total knee arthroplasty. MATERIAL AND METHODS: This meta-analysis was conducted according to the Cochrane methodology. Twenty-eight superior quality and well designed randomized controlled trials (RCT) were collected to analyze for this study. Patients who had undergone primary unilateral TKA were chosen. The software, RevMan 5.2, was used to analyze collected data. RESULTS: Finally, 28 RCTs were collected to analyze for this study. Total blood loss was dramatically decreased via the application of TA, by a mean of 420 ml [95% CI: -514 to -327]. A significant reduction about blood transfusion rate was also found in patients who received TA. [RD: -0.26, 95%CI: -0.33 to -0.19]. Moreover, no significant differences were found between TA and control groups in incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE). CONCLUSIONS: This meta-analysis demonstrates that the application of TA in TKA could decrease total blood loss and transfusion rate. On the other hand, the application of TA is not associated with high incidence of DVT or other adverse events. TA should be taken into account in routine use in primary knee arthroplasty to benefit the patients.

High extracellular magnesium inhibits mineralized matrix deposition and modulates intracellular calcium signaling in human bone marrow-derived mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have the potential to differentiate into several cell types and provide an attractive source of autologous cells for regenerative medicine. However, their cellular biology is not fully understood. Similar to Ca(2+), extracellular Mg(2+) plays an important role in the functions of the skeletal system. Here, we examined the effects of extracellular Mg(2+) on the deposition of calcium phosphate matrix and Ca(2+) signaling with or without ATP stimulation in human bone marrow-derived mesenchymal stem cells (hBMSCs). We found that high extracellular Mg(2+) concentration ([Mg(2+)]e) inhibited extracellular matrix mineralization in hBMSCs in vitro. hBMSCs also produced a dose-dependent decrease in the frequency of calcium oscillations during [Mg(2+)]e elevation with a slight suppression on oscillation amplitude. In addition, spontaneous ATP release was inhibited under high [Mg(2+)]e levels and exogenous ATP addition stimulated oscillation reappear. Taken together, our results indicate that high [Mg(2+)]e modulates calcium oscillations via suppression of spontaneous ATP release and inactivates purinergic receptors, resulting in decreased extracellular mineralized matrix deposition in hBMSCs. Therefore, the high magnesium environment created by the rapid corrosion of Mg alloys may result in the dysfunction of calcium-dependent physiology processes and be disadvantageous to hBMSCs physiology.

Case Report: Identification of Compound Heterozygous Mutations in a Patient With Late-Onset Glycogen Storage Disease Type II (Pompe Disease).

Pompe disease is an autosomal recessive hereditary lysosomal disorder and correlated with acid α-glucosidase enzyme (GAA) deficiencies, which lead to accumulation of glycogen in all tissues, most notably in skeletal muscles. Adult late-onset Pompe disease (LOPD) is a slowly progressive disease of proximal myopathy with later involvement of the respiratory muscles, resulting in respiratory failure. In this study, we reported a 22-year-old Chinese woman with inability to withstand heavy physical activity since childhood, who presented with respiratory and ambulation weakness in 2 months. On admission, her bilateral upper limbs strength was 4/5 and lower limbs strength was 3/5 according to Medical Research Council (MRC) score. The patient had compound heterozygotes containing a newly identified 4 nt deletion of coding sequence (deletion nt 1411_1414) in one of the acid α-glucosidase alleles and a c.2238G>C (p.Trp746Cys) missense mutation. This deletion has been reported in infant-onset Pompe disease (IOPD) but not LOPD. Intriguingly, this deletion mutation was not found in the patient's family and was considered as pathogenic. Muscle biopsy showed scattered vacuoles with basophilic granules inside the subsarcolemmal area, which were strongly stained by periodic acid-Schiff (PAS). Laboratory tests revealed a significant increase of creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH). GAA level was 9.77 nmol/1 h/mg and was not sufficient for the diagnosis of GAA activity deficiency (0-3.78 nmol/1 h/mg). In summary, mutational analysis of GAA and muscle biopsy are crucial in the diagnosis of Pompe disease.

Prevalence and Predictors of Chronic Pain with Two-Year Follow-Up After Knee Arthroplasty.

Background: Pain relief is the most important issue in the long-term outcome of arthroplasty surgery, with nearly one-third of patients still suffered persistent pain and caused dissatisfaction after the surgery. Methods: A total of 713 patients underwent primary elective primary TKA and UKA were included consecutively between July 2018 and December 2019, using binary logistic method to analyze the data. Results: The prevalence of CPSP at rest and on movement at 2-year was 12.1% and 37.7% respectively after primary knee arthroplasty and CPSP at rest factors included: age above 80 (odds ratio [OR]= 6.72, 95% confidence interval [CI] 1.58 to 28.56), BMI above 30 (2.339, 1.02 to 5.383), and moderate to severe pain variables: preoperative pain, (1.95, 1.11 to 3.41); APSP on movement, 4.9 (2.31-10.6); and follow-up contralateral knee pain-at-rest scores (12.6, 5.5 to 28.5). Factors associated with presence of CPSP on movement included: no smoking (2.59, 1.07 to 6.26); and moderate to severe pain variables: preoperative pain, (1.57, 1.073 to 2.30); APSP at rest, (1.85, 1.13 to 3.02); APSP on movement, 6.11 (3.82 to 9.78); and follow-up contralateral knee pain-on-movement scores, 3.22 (2.08 to 5.00). Factors to occurrence of moderate to severe CPSP on movement include: presence of COPD (12.20, 2.19 to 67.98); and moderate to severe pain variables: preoperative pain (2.36, 1.32 to 4.23); APSP on movement (4.68, 1.95 to 11.25); and follow-up contralateral knee pain-on-movement scores (2.71, 1.66 to 4.42). Conclusion: Prevention strategies should be targeted to different types of pain, and the comorbidity of COPD undergoing knee arthroplasty should receive early identification and attention.

Osteogenic differentiation of GFP-labeled human umbilical cord blood derived mesenchymal stem cells after cryopreservation.

The osteogenic capacity of human umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) has been demonstrated both in vitro and in vivo. Therefore, cell labeling and storage are becoming necessary for researching the potential therapeutic use of UCB-MSCs for bone tissue engineering. The aim of this study was to determine the effect of cryopreservation on the osteogenic differentiation of green fluorescent protein (GFP)-marked UCB-MSCs in vitro. MSCs were isolated from full-term human UCB, expanded, transfected with the GFP gene, and then cryopreserved in liquid nitrogen for 4 weeks. After thawing, cell surface antigen markers and osteogenic potential were analyzed, and the luminescence of these cells was observed by fluorescence microscopy. The results demonstrate that cryopreservation has no effect on the cell phenotype, GFP expression or osteogenic differentiation of UCB-MSCs, showing that cryopreserved GFP-labeled UCB-MSCs might be applied for bone tissue engineering.

Outcomes, and factors affecting outcomes, following shoulder hemiarthroplasty for proximal humeral fracture repair.

BACKGROUND: Hemiarthroplasty has been applied to treat proximal humeral fracture with variable outcomes. The purpose of this retrospective study was to assess factors affecting outcome in patients following hemiarthroplasty for proximal humeral fracture (PHF) repair. METHODS: Patients with proximal humeral fractures treated over a 6-year period were included. Indications for hemiarthroplasty were severe three-part fractures associated with osteoporosis; four-part fractures with or without dislocation; splitting of the humeral head, or >45% collapse of the humeral head. Surgery outcome and postoperative complications were main outcome measures in this study. RESULTS: Thirty-three of 47 patients were included in the final analysis (mean age 64.3 years, range 43-82). Mean postoperative follow-up was 44.4 (range 36-57) months. Postoperative complications (shoulder dislocation, mild shoulder subluxation, heterotopic ossification) occurred in seven patients. Healing of the greater and lesser tubercles was abnormal or poor in 18 patients. These patients had significantly higher pain scores (4.0 ± 1.1 vs. 2.2 ± 1.1) and significantly lower capacities for active lifting (79.3 ± 9.6 vs. 121.7 ± 24.3), external rotation (20.7 ± 3.7 vs. 39.2 ± 10.3), and Neer scores (79.2 ± 5.7 vs. 90.6 ± 3.6) versus patients who exhibited complete healing (all P < 0.001). Patient age, type of surgical approach, and fracture type were not major influencers of outcome. CONCLUSION: In conclusion, the healing of the greater and lesser tubercles is the major determinant of outcome following hemiarthroplasty for PHF repair.

Bilateral plate fixation for type C distal humerus fractures: experience at a single institution.

Type C fractures of the distal humerus are difficult to treat and typically require open anatomical reduction and internal fixation. Here we describe our experience treating patients with type C distal humerus fractures using a trans-olecranon approach with bilateral plate fixation. Fifty-six patients (30 males, 26 females; mean age 49.8 years) were treated over a period of six years. Thirteen fractures were open and 43 closed; all were caused by falls or traffic accidents. All operations were performed successfully with no intraoperative complications. Mean duration of follow-up was 30 months (range 6-70). Mean duration of fracture healing was 2.8 months (range 2-4). Forty-seven out of 56 patients (84%) suffered no postoperative complications. One patient exhibited symptoms of ulnar nerve injury following surgery (nine exhibited symptoms before and after surgery). Two patients had mild cubitus varus deformities, four delayed olecranon osteotomy site healing, and two heterotopic ossifications. In summary, complications were minimal and outcomes satisfactory in patients with type C distal humerus fractures who underwent bilateral plate fixation via a trans-olecranon approach.

Peripheral FGFR1 Regulates Myofascial Pain in Rats via the PI3K/AKT Pathway.

Myofascial pain syndrome (MPS) is a type of skeletal pain identified by myofascial trigger points (MTrPs). The formation of MTrPs is linked to muscle damage. The fibroblast growth factor receptor (FGFR1) has been found to cause pain sensitivity while repairing tissue damage. The aim of the current study was to explore the mechanism of FGFR1 in MTrPs. We used a RayBio human phosphorylation array kit to measure p-FGFR1 levels in human control subjects and patients with MTrPs. P-FGFR1 was upregulated in the patients with MTrPs. Then a rat model of MPS was established by a blunt strike on the left gastrocnemius muscles (GM) and eccentric-exercise for 8 weeks with 4 weeks of recovery. After establishing the MPS model, the morphology of the GM changed, and the differently augmented sizes of round fibers (contracture knots) in the transverse section and fusiform shapes in the longitudinal section were clearly seen in the rats with myofascial pain. The expression of p-FGFR1 was upregulated on the peripheral nerves and dorsal root ganglion neurons in the MTrPs group. The spinal Fos protein expression was increased in the MTrPs group. Additionally, the mechanical pain threshold was reduced, and the expression of FGF2, p-FGFR1, PI3K-p110γ, and p-AKT increased in the MTrPs group. PD173074 increased the mechanical pain threshold of the MTrPs group, and inhibited the expression of p-FGFR1, PI3K-p110γ, and p-AKT. Moreover, LY294002 increased the mechanical pain threshold of the MTrPs group. These findings suggest that FGFR1 may regulate myofascial pain in rats through the PI3K/AKT pathway.

Inhibition of Peripheral ERK Signaling Ameliorates Persistent Muscle Pain Around Trigger Points in Rats.

The purpose of this study was to investigate whether the ERK signaling pathway was involved in ameliorating chronic myofascial hyperalgesia from contused gastrocnemius muscle in rats. We established an animal model associated with myofascial pain syndrome and described the mechanism of muscle pain in an animal model. Changes in the mechanical pain threshold were observed 0.5, 1, 2, 3, 4, 5, 8, 12, 18, and 24 h after ERK inhibitor injection around myofascial trigger points (MTrPs) of the gastrocnemius muscle in rats. Morphological changes in gastrocnemius muscle cells were observed by hematoxylin and eosin (H&E) staining. ERK signaling pathway activation was detected through immunohistochemistry and Western blotting. The main morphological characteristics of injured muscle fibers around MTrPs include gathered circular or elliptical shapes of different sizes in the cross-section and continuous inflated and tapering fibers in the longitudinal section. After intramuscular injection of U0126 (ERK inhibitor), the mechanical pain threshold significantly increased. The reduction in mechanical hyperalgesia was accompanied by reduced ERK protein phosphorylation, myosin light chain kinase (MLCK) protein, p-MLC protein expression, and the cross-sectional area of skeletal muscle cells around MTrPs. An ERK inhibitor contributed to the attenuation of mechanical hyperalgesia in the rat myofascial pain model, and the increase in pain threshold may be related to MLCK downregulation and other related contraction-associated proteins by ERK.

Ideal intraarticular application dose of tranexamic acid in primary total knee arthroplasty: a prospective, randomized and controlled study.

BACKGROUND: Combined use of tranexamic acid (TXA) via intravenous (IV) and intraarticular (IA) routes is more effective in reducing blood loss than any single route in primary total knee arthroplasty (TKA), but the optimal dose of topical administration remains controversial. The aim of this study was to evaluate the efficacy and safety of different combined administration strategies and to determine an ideal IA application dose of TXA. METHODS: A total of 180 patients who underwent primary TKA were randomized to four groups (groups A/B/C/D) with the same single IV dose of 1 g TXA preoperatively and four different IA doses after wound closure: group A (0 g), group B (1 g), group C (2 g), and group D (4 g). The primary outcome measures included wound blood drainage, hemoglobin (Hb) concentration, and blood transfusion. The secondary outcome measures included wound complications, deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE). RESULTS: A total of 165 patients finished at least 3 months of follow-up visits. The amount of 48-hour blood drainage and calculated total blood loss in four groups decreased with the increased dose of TXA injected via IA route, and no difference was observed between groups C and D (P=0.6237 and P=0.9923, respectively). Hb was significantly higher in groups C and D than in groups A and B at postoperative day 1, 3 and 7, respectively (P<0.0001). Hb in group A was significantly lower than that in groups C and D at 1 month after surgery, whereas no intergroup difference was found in other groups. No intergroup difference was observed regarding DVT, PE or wound complications. CONCLUSIONS: The topical injection of 2 g TXA may have reached the "ceiling effect" of local use. A preoperative IV dose of 1 g TXA combined with an IA dose of 2 g TXA could be an optimal combination regimen.

[Treatment of AO/OTA type 31-A3 intertrochanteric fracture with proximal femoral nail antirotation combined with mini plate reconstruction of lateral femoral wall].

OBJECTIVE: To explore the effectiveness of proximal femoral nail antirotation (PFNA) combined with mini plate for reconstruction of lateral femoral wall in the treatment of type AO/Orthopaedic Trauma Association (AO/OTA) type 31-A3 intertrochanteric fracture. METHODS: The clinical data of 70 elderly patients with AO/OTA type 31-A3 intertrochanteric fracture treated between January 2013 and January 2018 were retrospectively analyzed. They were divided into group A (PFNA alone, 35 cases) and group B (PFNA combined with mini plate reconstruction of lateral femoral wall, 35 cases). There was no significant difference in the general data of gender, age, side, cause of injury, time from injury to operation between the two groups ( P>0.05). The operation time, intraoperative blood loss, fracture healing time, postoperative complications, and the tip apex distance (TAD) at 2 months after operation were recorded and compared between the two groups. Harris hip score was used to evaluate the function at 12 months after operation. RESULTS: Both groups were followed up 9-21 months, with an average of 16.6 months. The operation time and intraoperative blood loss in group A were significantly less than those in group B ( P<0.05); there was no significant difference in TAD between the two groups at 2 months after operation ( t=0.096, P=0.462). There were 5 complications (14.3%) occurred in group A, including 2 cases of blade perforating from the hip joint, 2 cases of screw back out, and 1 case of bone nonunion; only 1 case (2.9%) in group B had screw back out after operation; there was no significant difference in the incidence of complications between the two groups ( χ 2=2.917, P=0.088). All the fracture healed in group B, and 1 patient in group A suffered bone nonunion and eventually main nail fracture. The healing time of fracture in group A [(15.6±2.7) weeks] was significantly longer than that in group B [(12.5±2.5) weeks], showing significant difference ( t=2.064, P=0.023). At 12 months after operation, according to Harris score, the results were excellent in 5 cases, good in 9 cases, fair in 13 cases, and poor in 8 cases in group A, the qualified rate (Harris score>70) was 77.14%; and the results were excellent in 7 cases, good in 11 cases, fair in 16 cases, and poor in 1 case in group B, the qualified rate was 97.14%; there was significant difference in the qualified rate between the two groups ( χ 2=6.248, P=0.012). CONCLUSION: Compared with PFNA alone, the treatment of AO/OTA type 31-A3 intertrochanteric fracture with PFNA combined with mini plate reconstruction of lateral femoral wall can significantly reduce postoperative complications, promote fracture healing, and improve functional recovery of patients after operation.

Hydroxypropylcellulose Coating to Improve Graft-to-Bone Healing for Anterior Cruciate Ligament Reconstruction.

An anterior cruciate ligament (ACL) injury is one of the most common injuries in sports, and ACL reconstruction with an artificial ligament is a good treatment for quick recovery. However, current artificial ligaments made of polyethylene terephthalate (PET) are still associated with some problems due to the hydrophobic nature and low biological induction activity of PET. Many efforts have been used to improve the biocompatibility of PET in recent years, and our previous work has shown that surface modification is an effective strategy. Here, a hydroxypropylcellulose (HPC) coating was applied on the surface of a PET artificial ligament order to improve its biocompatibility. The effects of the HPC coating on PET artificial ligament graft-bone healing was investigated in vitro using bone marrow stromal cells (BMSCs), fibroblasts, and RSC-364 cells as well as in vivo in a beagle dog model of ACL reconstruction. HPC was coated successfully on the PET and significantly promoted cell growth, adhesion, and capability of osteogenic differentiation compared to the PET graft without HPC coating. In vivo, the HPC coating significantly enhanced ligament tissue regeneration. Moreover, higher expression of some bone-formation- and ligament-tissue-regeneration-contributing proteins and cell factors, such as COL1, BMP-7, COL3, OCN, RUNX2, TGF-ß1, and VEGF, was observed on the HPC-coated PET artificial ligament in comparison with the pure PET artificial ligament. In conclusion, HPC coating can significantly improve the cytocompatibility and graft-to-bone healing of a PET artificial ligament for ACL reconstruction.

MicroRNA­218 promotes prostaglandin E2 to inhibit osteogenic differentiation in synovial mesenchymal stem cells by targeting 15­hydroxyprostaglandin dehydrogenase [NAD(+)].

The chondrogenic differentiation of synovial mesenchymal stem cells (SMSCs) is regulated by essential transcription factors and signaling cascades. However, the precise mechanisms involved in this process remain unclear. MicroRNAs (miRs/miRNAs) are undersized non­coding RNAs responsible for the post­transcriptional regulation of gene expression, by binding to the 3'­untranslated regions (3'­UTRs) of their target mRNAs. miRNAs may constitute a promising tool to regulate SMSC differentiation and to advance the controlled differentiation of SMSCs in therapeutic applications. The aim of the present study was to examine the role of miR­218 in SMSC differentiation towards chondrocytes. The present study comparatively analyzed the expression profile of known miRNAs and specific target genes in SMSCs between early and late differentiation stages. Western blotting and reverse transcription­quantitative polymerase chain reaction analysis of gene expression demonstrated the upregulation of 15­hydroxyprostaglandin dehydrogenase [NAD(+)] (15­HPGD), prostaglandin E2 (PGE2) and rate limiting enzymes responsible for the synthesis of PGE2 precursors throughout chondrogenesis. Through correlation analysis, it was observed that there was a significant association between miR­128, 15­HPGD gene expression, 15­HPGD protein expression and microsomal prostaglandin E synthase 1. Further experiments demonstrated that miR­218 decreased PGE2 concentration by binding to the 3'­UTR of 15­HPGD. Using an immunofluorescence reporting system, it was observed that miR­218 regulated the expression of 15­HPGD during the differentiation of SMSCs into cartilage, and subsequently inhibited osteogenesis during chondrogenesis by acting on the 3'UTR of 15­HPGD. Therefore, miR­218 may be an important regulator targeting osteogenic factors and modulating cartilage formation and differentiation. The results of the present study provided a novel insight beneficial to cellular manipulation methods during cartilage regeneration, and in cartilage tissue engineering research.

Meta-Analysis on Microdiscectomy and Sequestrectomy for Lumbar Disc Herniation.

PURPOSE: Lumbar disc herniation (LDH) is a common cause of low back pain and mainly occurs in patients aged 24 to 45 years. To further compare the efficacy of microdiscectomy and sequestrectomy, we made quantitative evaluation of clinical studies published so far by meta-analysis in order to provide information for clinical decision. METHODS: Literatures reporting randomized controlled studies that compared the efficacy of microdiscectomy and sequestrectomy for LDH were retrieved from major databases using predefined inclusion and exclusion criteria. RESULTS: Meta-analysis showed that microdiscectomy resulted in higher low back pain VAS score (standard mean difference, SMD = 0.86, 95% confidential interval, CI: 0.19, 1.53; P = 0.01) and there was not statistically significant difference in the incidence of re-operation (odd ratio, OR = 0.85, 95% CI: 0.46, 1.85; P = 0.60) and neuropathic pain VAS scores (SMD = 0.51, 95% CI: -0.16, 1.18; P = 0.14) between the methods. CONCLUSION: Both microdiscectomy and sequestrectomy had good curative results in the treatment of LDH. In low back pain VAS score, the former was better than the latter, while in the analgesic usage rate, the latter was superior to the former. In clinical practice, the choice of surgical method should be considered on the basis of actual situations.

Parathyroid hormone plus alendronate in osteoporosis: a meta-analysis of randomized controlled trials.

BACKGROUND: Parathyroid hormone (PTH) increases both bone formation (BMD) and bone resorption, whereas alendronate reduces bone resorption. It is possible that the combination therapy of PTH with alendronate will enhance their effects on BMD. Therefore, we conducted this meta-analysis to evaluate the efficacy of the combination therapy of PTH with alendronate in the treatment of patients with osteoporosis. METHODS: A comprehensive literature search of PubMed, Embase, and Web of Science was conducted to identify relative studies. Eligible studies were randomized controlled trials (RCT), which assessed the efficacy of combination therapy in patients with osteoporosis. The outcomes included the mean percent increases in BMD of lumbar spine, femoral neck, total hip, and distal radius. Weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated using of random-effects or fixed-effects model, depending on the heterogeneity between the included studies. RESULTS: Six RCTs with a total number of 833 patients were included in this meta-analysis. The pooled estimates showed that, the combination therapy of PTH with alendronate resulted in a higher mean percent change of increased BMD in distal radius (WMD = 2.45, 95% CI: 1.58, 3.31; P = 0.000), but not in lumbar spine (WMD = -0.83, 95% CI: -3.48, 1.81; P = 0.538), femoral neck (WMD = -0.99, 95% CI: -2.04, 0.07; P = 0.068), and total hip (WMD = -0.06, 95% CI: -0.93, 0.81; P = 0.892). The subgroup analysis based on the dosage and schedule of PTH, study duration, gender of patients, and anabolic agents, were conducted. And results revealed that among the patients in the combination therapy group, greater increases in the spine BMD were observed when the PTH was administered with a dosage of 20 µg (WMD = 2.33, 95% CI: 1.24, 3.43; P = 0.000), or the treatment duration lasted more than 12 months (WMD = 2.23, 95% CI: 1.00, 3.47; P = 0.000), or the combination therapy was used in osteoporosis women (WMD = 1.58, 95% CI: 0.63, 2.53; P = 0.001). However, the combination of PTH of 40 µg with alendronate produced a decrease in the BMD at spine (WMD = -4.56, 95% CI: -7.56, -1.56; P = 0.003) and femoral neck (WMD = -5.82, 95% CI: -9.91, -1.72; P = 0.005). CONCLUSION: Our findings indicated that the addition of alendronate to PTH in the treatment of osteoporosis, reduced the ability of PTH therapy to increase the BMD at the lumbar spine, femoral neck, and total hip.