Upregulated miR-125b mitigates inflammation, astrocyte activation, and dysfunction of spinal cord injury by inactivating the MAPK pathway.

BACKGROUND: Since the abnormal expression of miR-125b in spinal cord injury (SCI) and the regulatory effect of miR-125b on the MAPK pathway have been expounded, we attempt to investigate whether miR-125b exerts a regulatory effect on SCI by modulating the MAPK pathway. METHOD: A SCI rat model was established. The rats were treated with miR-125b antagomir or agomir, and their motor function affected by miR-125b was further detected by Basso-Beattie-Bresnahan (BBB) scoring. The histopathological changes and neuronal loss in the spinal cord were evaluated using hematoxylin-eosin and Nissl staining. Microglia-conditioned medium (MCM) was prepared and further used to treat the astrocytes, the activation of which was evaluated via immunofluorescence staining. The expressions of miR-125b, inflammation-related factors (IL-6, IL-1ß, TNF-α, and IL-10), and MAPK pathway-related proteins (p38, ERK1/2, and JNK1/2 as well as their phosphorylated (p) forms) in the spinal cord, serum, and MCM-treated astrocytes of rats were determined by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay, and Western blot. RESULT: MiR-125b was lowly expressed in SCI-modeled rats. MiR-125b downregulation aggravated the impaired motor function, the disorder within the tissue, astrocyte activation, and neuron loss in the spinal cord tissues of SCI-modeled rats, while miR-125b upregulation did oppositely. MiR-125b downregulation enhanced the levels of IL-6, IL-1ß, TNF-α, p38, p-p38, p-ERK1/2, and p-JNK1/2, whilst reducing that of IL-10. Contrarily, miR-125b upregulation exerted the opposite effects in SCI-modeled rats and MCM-treated astrocytes. CONCLUSION: Up-regulation of miR-125b mitigates inflammation, astrocyte activation, and dysfunction in SCI by inactivating the MAPK pathway.

TRAF2 gene silencing induces proliferation and represses apoptosis of nucleus pulposus cells in rats with intervertebral disc degeneration.

OBJECTIVE: We aim to research the role of TRAF2 silencing in regulating proliferation and apoptosis of nucleus pulposus cells (NIPCs) in rats with intervertebral disc degeneration (IDD) through mediating NF-κB signaling pathway. METHODS: Degenerative disc nucleus pulposus tissues and normal nucleus pulposus tissues were collected to compare the positive expression of TRAF2 protein by immunohistochemistry, and to compare TRAF2, NF-κB (P65) and NF-κB (P50) expression by RT-qPCR and Western blot. A rat model with IDD was replicated using fibrous ring needle method and then treated with TRAF2-siRNA to silence TRAF2. Then, pathological changes and apoptosis in nucleus pulposus tissues were observed. In vitro NIPCs were transfected with TRAF2-siRNA or NF-κB pathway activator (recombinant TNF-α), and then colony formation, proliferation, senescence and apoptosis of NIPCs were determined. RESULTS: Increased TRAF2 and NF-κB were found in nucleus pulposus tissues from IDD patients and rats. Silencing TRAF2 inactivated NF-κB signaling pathway and attenuated pathological damage and apoptosis in nucleus pulposus tissues of rats with IDD. In in-vitro NIPCs, knockdown of TRAF2 resulted in promoted proliferation and colony formation ability while suppressed senescence and apoptosi. The NF-κB pathway activator (recombinant TNF-α) reversed the phenotypic changes of NIPCs resulted from TRAF2 silence. CONCLUSION: Our study demonstrates that TRAF2 is highly expressed in IDD, and silencing of TRAF2 promotes NIPC proliferation and restrains the apoptosis in IDD.

Thyrotoxicosis and osteomalacia: from symptom to pathogenesis.

Thyroid hormones have a direct effect on bone mineral homeostasis, leading to increased bone mineral resorption and calcium loss through the kidneys. Osteomalacia is conceptualized as a disorder of bone tissue characterized by inadequate or delayed mineralization of osteoid in mature cortical and spongy bone, and is associated with thyrotoxicosis. This article assessed the impact of thyrotoxicosis on the occurrence and development of osteomalacia for better diagnosis and treatment of the disease. We searched databases such as Pubmed with "osteomalacia" and "thyrotoxicosis", 15 papers were found; with "osteopenia" or "osteomalacia" or "osteoporosis" and "thyrotoxicosis", 129 papers were found. The causes of osteomalacia include insufficient intake of calcium, phosphorus and vitamin D, impaired absorption and metabolism of vitamin D, kidney diseases (nephrotic syndrome, chronic renal failure, renal tubular acidosis, Fanconi syndrome, etc.), hereditary and neoplastic hypophosphatemia, and other diseases such as heavy metal poisoning, high fluoride intake. At present, the pathogenesis of osteomalacia caused by thyrotoxicosis are mainly attributed to catabolism of vitamin D, vitamin D deficiency and mechanisms underlying calcium metabolism disorder. Since thyrotoxicosis can cause osteopenia and may coexist with osteomalacia, attention should be given to the changes of alkaline phosphatase, liver function and clinical symptoms. If necessary, chest X-ray and pelvic X-ray should be carried out to find out potential osteomalacia for timely treatment to avoid the occurrence of fracture and even deformity.

Endometrial adenocarcinoma metastatic to the pituitary gland: a case report and literature review.

Pituitary metastases are rare, and metastatic pituitary lesions originating from endometrial adenocarcinoma are extremely rare. These lesions can be mistaken for pituitary adenomas and their diagnosis can be very difficult. Pituitary metastases mostly affect the posterior lobe and patients may develop diabetes insipidus. Patients with endometrial cancer complicated with diabetes, including poor glycemic control, may also suffer from thirst, making it more difficult to diagnose diabetes insipidus. A 68-year-old woman who was being followed-up for primary endometrial adenocarcinoma was admitted for gradually worsened polyuria and polydipsia. Her laboratory findings were compatible with diabetes insipidus. Magnetic resonance imaging revealed thickening of the pituitary stalk, involvement of the superior pituitary gland, and disappearance of hyperintensity in the posterior lobe, indicating pituitary metastasis. Increased urine output and oral fluid intake in a patient with a diagnosis of carcinoma may indicate possible pituitary metastasis, and the hormonal insufficiency should be corrected to improve the patient's quality of life.

Partial Recovery of Limb Function Following End-to-Side Screw Anastomosis of Phrenic Nerve in Rats with Brachial Plexus Injury.

BACKGROUND Brachial plexus injury (BPI), a severe nervous system injury, is a leading cause of functional damages of the affected upper limb. Patients with BPI manifested with motor weakness or paralysis, sensory deficits, and pain. We established a BPI rat model to explore the in vivo effect of end-to-side screw anastomosis (ETSSA) of phrenic nerve on the recovery of limb function after BPI. MATERIAL AND METHODS After modeling, rats were treated with end-to-side anastomosis (ETSA) and ETSSA respectively. After 1 and 3 months, the behavioral changes of rats were observed using the Terzis grooming test, and the compound muscle action potential (CMAP) and muscle tension of biceps brachii were detected. The muscle weight recovery rate (MWRR) and cross-sectional area recovery rate (CARR) were calculated. Toluidine blue staining was used to observe the myelinated nerve fibers in the proximal phrenic nerve and distal musculocutaneous nerve of suture. The ratio of regenerated nerve traversing rate (NTR) was counted and motor endplate area of biceps brachii was measured. RESULTS The rats treated with ETSA and ETSSA exhibited elevated grading of Terzis grooming test with time. Although both the ETSSA and ETSA can reduce the MWRR, CARR and motor endplate area in BPI rats, ETSSA showed a better influence on the latency delayed rate (LDR) and amplitude recovery rate (ARR) of CMAP, muscular tension recovery rate (MTRR), MWRR, number of regenerated myelinated nerve fibers, NTR, and motor endplate area in BPI rats. CONCLUSIONS Our study provided evidence that ETSSA can restore the limb function recovery to a greater extent, and accelerate the regeneration of nerve fibers in rats with BPI; the effect of ETSSA was better than that of ETSA.

Tibial tunnel enlargement and joint instability after anterior cruciate ligament reconstruction. A prospective comparison between autograft and allograft

Abstract Purpose: To investigate tibial tunnel widening and knee instability after ACL reconstruction with hamstring autograft or irradiated soft tissue allograft. Methods: Eight-two patients were divided into two groups: autograft group and allograft group. Radiographic and clinical evaluations were performed. Results: Seventy patients were followed up with median of 36.3 months (range 36-38 months). Tibial tunnel widening was at or greater than 30% for nine patients in the autograft group and 15 patients in the allograft group (P = 0.0417). The average percentage of tibial tunnel widening was 26.7 ± 4.0 % and 29.7 ± 5.3 % in autograft and allograft groups, respectively (P = 0.0090). Knee range of motion was not affected by the reconstruction operation or different grafts. Thigh atrophy improved significantly within 24 months after ACL reconstructions in both groups. ACL reconstruction with the allograft leaded to less knee stability than that with the autograft from one year after operation (P = 0.0023). There was no significant difference between two groups with respect to Lysholm score (P = 0.1925) and Tegner score (P =0 .0918) at the final follow-up. Conclusion: The allograft group reported significantly more tibial tunnel widening and knee instability compared with the autograft group.

Vitamin K intake and the risk of fractures: A meta-analysis.

The association between dietary vitamin K intake and the risk of fractures is controversial. Therefore we perform a meta-analysis of cohort or nested case-control studies to investigate the relationship between dietary vitamin K intake and the risk of fractures. A comprehensive search of PubMed and EMBASE (to July 11, 2016) was performed to identify cohort or nested case-control studies providing quantitative estimates between dietary vitamin K intake and the risk of fractures. Summary relative risk (RRs) with corresponding 95% confidence intervals (CIs) were pooled by using a random-effects model. Four cohort studies and one nested case-control study, with a total of 1114 fractures cases and 80,982 participants, were included in our meta-analysis. Vitamin K intake in all included studies refers exclusively to the intake of phylloquinone (vitamin K1), which is the predominant form of vitamin K in foods. We observed a statistically significant inverse association between dietary vitamin K intake and risk of fractures (highest vs. the lowest intake, RR = 0.78, 95% CI: 0.56-0.99; I = 59.2%, P for heterogeneity = .04). Dose-response analysis indicated that the pooled RR of fracture for an increase of 50 µg dietary vitamin K intake per day was 0.97 (95% CI: 0.95-0.99) without heterogeneity among studies (I = 25.9%, P for heterogeneity = .25). When stratified by follow-up duration, the RR of fracture for dietary vitamin K intake was 0.76 (95% CI: 0.58-0.93) in studies with more than 10 years of follow-up. Our study suggests that higher dietary vitamin K intake may moderately decrease the risk of fractures.

Tibial tunnel enlargement and joint instability after anterior cruciate ligament reconstruction. A prospective comparison between autograft and allograft.

PURPOSE: To investigate tibial tunnel widening and knee instability after ACL reconstruction with hamstring autograft or irradiated soft tissue allograft. METHODS: Eight-two patients were divided into two groups: autograft group and allograft group. Radiographic and clinical evaluations were performed. RESULTS: Seventy patients were followed up with median of 36.3 months (range 36-38 months). Tibial tunnel widening was at or greater than 30% for nine patients in the autograft group and 15 patients in the allograft group (P = 0.0417). The average percentage of tibial tunnel widening was 26.7 ± 4.0 % and 29.7 ± 5.3 % in autograft and allograft groups, respectively (P = 0.0090). Knee range of motion was not affected by the reconstruction operation or different grafts. Thigh atrophy improved significantly within 24 months after ACL reconstructions in both groups. ACL reconstruction with the allograft leaded to less knee stability than that with the autograft from one year after operation (P = 0.0023). There was no significant difference between two groups with respect to Lysholm score (P = 0.1925) and Tegner score (P =0 .0918) at the final follow-up. CONCLUSION: The allograft group reported significantly more tibial tunnel widening and knee instability compared with the autograft group.

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 will enhance their effects on BMD. Therefore, we conducted this meta-analysis to evaluate the efficacy of the combination therapy in osteoporosis. METHODS: A comprehensive literature search of Pubmed, Embase, and Web of Science was conducted to identify relative studies. The outcomes included the mean percent increases in BMD of lumbar spine, femoral neck, total hip, and distal radius. A fixed-effects model or random-effects was used to pool the estimates according to the heterogeneity. RESULTS: Six RCTs with a total number of 833 patients were included in this meta-analysis. The pooled estimates showed that, the combination therapy resulted in a higher mean percent change of increased BMD in distal radius (WMD = 2.45, 95%CI: 1.58, 3.31; 0.000), but not in lumbar spine (WMD = -0.83, 95%CI: -3.48, 1.81; p = .538), femoral neck (WMD = -0.99, 95%CI: -2.04, 0.07; p = .068), and total hip (WMD = -0.06, 95%CI: -0.93, 0.81; p = .892). Subgroup analysis 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 = .000), or the treatment duration lasted more than 12 months (WMD = 2.23, 95%CI: 1.00, 3.47; p = .000), or the combination therapy was used in osteoporosis women (WMD = 1.58, 95%CI: 0.63, 2.53; p = .001). CONCLUSION: Our findings indicated that combination therapy in the treatment of osteoporosis, reduced the ability of PTH therapy to increase the BMD at the lumbar spine, femoral neck, and total hip.

The association between the ACTN3 R577X polymorphism and noncontact acute ankle sprains.

Ankle sprains are one of the most severe musculoskeletal soft tissue injuries during physical activity. Although many risk factors have been offered, it is unclear why some individuals develop noncontact ankle sprains when participating in comparable levels of physical exertion under identical environmental conditions and others do not. The ACTN3 gene that encodes the α-actinin-3 protein, which is, only expressed in the Z line of fast glycolytic muscle fibres was found to associate with power/strength performance. The aim of this study was therefore to investigate whether the ACTN3 gene polymorphism is associated with noncontact acute ankle sprains. One hundred and forty-two participants with clinically diagnosed noncontact acute ankle sprains as well as 280 physically active controls participants without any history of ankle sprains were included in this case-control genetic association study. The RR genotype (odds ratio (OR) = 0.56; 95% confidence interval (CI), 0.32-0.65, P = 0.011) and R allele (OR = 0.64; 95% CI, 0.37-0.68, P = 0.002) of the ACTN3 were significantly low-represented in the acute ankle sprains group compared with the control group. The ACTN3 R577X is associated with acute ankle sprains in Chinese participants in this study. This is the first study to suggest that an individual with a RR genotype is at a decreased risk of acute ankle sprains.

Polymorphism of the low-density lipoprotein receptor-related protein 5 gene and fracture risk.

Several molecular epidemiological studies have been conducted to examine the association between low-density lipoprotein receptor-related proteins (LRP5) Ala1330Val polymorphism and fracture; however, the conclusions remained controversial. We therefore performed an extensive meta-analysis on 10 published studies with 184479 subjects. Electronic databases, including PubMed, Excerpta Medica Database (EMBASE), Cochrane, Elsevier Science Direct and China National Knowledge Infrastructure (CNKI) databases were searched. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using random-effects models. LRP5 Ala1330Val polymorphism was associated with a significantly increased risk of fracture (OR = 1.10; 95% CI, 1.06-1.14; I(2) = 29%). We also found that this polymorphism increased fracture risk in Caucasians. In the subgroup analysis according to gender, women was significantly associated with risk of fracture. In the subgroup analysis by type of fracture, LRP5 Ala1330Val polymorphism showed increased osteoporotic fracture risk. In conclusion, this meta-analysis suggested that an increased risk of fracture was associated with the LRP5 Ala1330Val polymorphism.