The N-Myc-responsive lncRNA MILIP promotes DNA double-strand break repair through non-homologous end joining.

The protooncoprotein N-Myc, which is overexpressed in approximately 25% of neuroblastomas as the consequence of MYCN gene amplification, has long been postulated to regulate DNA double-strand break (DSB) repair in neuroblastoma cells, but experimental evidence of this function is presently scant. Here, we show that N-Myc transcriptionally activates the long noncoding RNA MILIP to promote nonhomologous end-joining (NHEJ) DNA repair through facilitating Ku70-Ku80 heterodimerization in neuroblastoma cells. High MILIP expression was associated with poor outcome and appeared as an independent prognostic factor in neuroblastoma patients. Knockdown of MILIP reduced neuroblastoma cell viability through the induction of apoptosis and inhibition of proliferation, retarded neuroblastoma xenograft growth, and sensitized neuroblastoma cells to DNA-damaging therapeutics. The effect of MILIP knockdown was associated with the accumulation of DNA DSBs in neuroblastoma cells largely due to decreased activity of the NHEJ DNA repair pathway. Mechanistical investigations revealed that binding of MILIP to Ku70 and Ku80 increased their heterodimerization, and this was required for MILIP-mediated promotion of NHEJ DNA repair. Disrupting the interaction between MILIP and Ku70 or Ku80 increased DNA DSBs and reduced cell viability with therapeutic potential revealed where targeting MILIP using Gapmers cooperated with the DNA-damaging drug cisplatin to inhibit neuroblastoma growth in vivo. Collectively, our findings identify MILIP as an N-Myc downstream effector critical for activation of the NHEJ DNA repair pathway in neuroblastoma cells, with practical implications of MILIP targeting, alone and in combination with DNA-damaging therapeutics, for neuroblastoma treatment.

Visceral and ectopic fat are more predictively associated with primary liver cancer than overall obesity from genetic sights: A Mendelian randomization study.

Several observational studies have reported an association between obesity and primary liver cancer (PLC), while the causality behind this association and the comparison of the risk effects of different obesity indicators on PLC remain unclear. In this study, we performed two-sample Mendelian randomization (MR) analyses to assess the associations of genetically determined liver fat, visceral adipose tissue (VAT), and body mass index (BMI) with the risk of PLC. The summary statistics of exposures were obtained from two genome-wide association studies (GWASs) based on the UK Biobank (UKB) imaging cohort and the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. GWAS summary statistics for PLC were obtained from FinnGen consortium R7 release data, including 304 PLC cases and 218 488 controls. Inverse-variance weighted (IVW) was used as the primary analysis, and a series of sensitivity analyses were performed to further verify the robustness of these findings. IVW analysis highlighted a significant association of genetically determined liver fat (OR per SD increase: 7.14; 95% CI: 5.10-9.99; P = 2.35E-30) and VAT (OR per SD increase: 5.70; 95% CI: 1.32-24.72; P = .020) with PLC but not of BMI with PLC. The findings were further confirmed by a series of MR methods. No evidence of horizontal pleiotropy between these associations existed. Our study suggested that genetically determined liver fat and VAT rather than BMI were associated with an increased risk of PLC, which suggested that visceral fat distribution is more predictive of the clinical risk of PLC than common in vitro measures.

Mst1 attenuates myocardial ischemia/reperfusion injury following heterotopic heart transplantation in mice through regulating Keap1/Nrf2 axis.

Ischemia reperfusion (I/R) injury remains a frequent adverse event that accompanies heart transplantation. Oxidative stress and aberrant production of free radicals were regarded as the culprit of cell death and tissue damage in post-transplant IR injury. Mst1 has been identified as a mediator of oxidative stress and Nrf2 regulates anti-oxidative enzymes, however, the interaction between Mst1 and Nrf2 anti-oxidative stress pathway remains to be clarified in the event of cardiac IR injury. Herein, the model of ischemia-reperfusion injury in heterotopic heart transplantation mice was firstly established.. We observed that cardiac IR induced upregulation of Mst1 and activation of Nrf2/HO-1pathway in mice receiving heterotopic heart transplantation. Further Cobalt dichloride-induced oxidative stress model of RAW264.7 macrophage cells were then established to mimic cardiac I/R injury, results showed that exposure to CoCl2 induced the upregulation of Mst1 and activation of Keap1/Nrf2 pathway, and genetic ablation of Mst-1 and inhibition of Keap1/Nrf2 pathway aggravated oxidative damage in those cells. Additional in vivo study showed that transfection of Mst1 shRNA spurred ROS generation and worsened cardiac damage in IR mice. Meanwhile, Mst1-KD mice receiving heart transplantation showed markedly downregulation of Nrf2, HO-1 yet upregulation of Keap1, indicating diminished protective effect against tissue damage caused by IR probably owing to the frustration of Keap1/Nrf2 pathway. Taken together, our findings demonstrated the protective effect of Mst1 from cardiac IR injury via triggering Keap1/Nrf2 axis and suppressing ROS generation, which shed light on the promising role of Mst1 in transitional management of IR injury resulted from cardiac transplantation.

Short- and long-term outcomes of laparoscopic versus open liver resection for large hepatocellular carcinoma: a propensity score study.

PURPOSE: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) remains controversial, especially for tumors larger than 5 cm. We compared the short- and long-term outcomes of laparoscopic and open liver resection (OLR) for large HCC. METHODS: Patients with large HCC after curative hepatectomy were enrolled. To compare the short-term outcomes, propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were performed to reduce the effect of confounding factors, respectively. Subsequently, Cox-regression analyses were conducted to identify the independent risk factors associated with decreased recurrence-free survival (RFS) and poor overall survival (OS). RESULT: There were 265 patients enrolled in the final analysis: 146 who underwent OLR and 119 who underwent LLR. There was no significant difference between the OLR and LLR groups according to PSM and IPTW analysis (all P > 0.05). Multivariable analysis revealed that LLR was not independently associated with poorer OS (HR 1.15, 95% CI 0.80-1.67, P = 0.448) or RFS (HR 1.22, 95% CI 0.88-1.70, P = 0.238). CONCLUSION: There were no significant differences in perioperative complications or long-term prognosis between LLR and OLR for large HCC, which provides evidence for standard laparoscopic surgical practice with adequate surgeon experience and careful patient selection.

Preoperative prediction model for microvascular invasion in HBV-related intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: Preoperative prediction of microvascular invasion (MVI) using a noninvasive method remain unresolved, especially in HBV-related in intrahepatic cholangiocarcinoma (ICC). This study aimed to build and validate a preoperative prediction model for MVI in HBV-related ICC. METHODS: Patients with HBV-associated ICC undergoing curative surgical resection were identified. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors of MVI in the training cohort. Then, a prediction model was built by enrolling the independent risk factors. The predictive performance was validated by receiver operator characteristic curve (ROC) and calibration in the validation cohort. RESULTS: Consecutive 626 patients were identified and randomly divided into the training (418, 67%) and validation (208, 33%) cohorts. Multivariate analysis showed that TBIL, CA19-9, tumor size, tumor number, and preoperative image lymph node metastasis were independently associated with MVI. Then, a model was built by enrolling former fiver risk factors. In the validation cohort, the performance of this model showed good calibration. The area under the curve was 0.874 (95% CI: 0.765-0.894) and 0.729 (95%CI: 0.706-0.751) in the training and validation cohort, respectively. Decision curve analysis showed an obvious net benefit from the model. CONCLUSION: Based on clinical data, an easy model was built for the preoperative prediction of MVI, which can assist clinicians in surgical decision-making and adjuvant therapy.

Successful intravenous thrombolysis for acute ischemic stroke caused by aortic dissection with severe hypofibrinogenemia: a case report and literature review.

BACKGROUND: Intravenous thrombolysis (IVT) for acute brain infarctions caused by aortic dissection (AD) may lead to fatal outcomes; thus, it should be ruled out, especially if hypofibrinogenemia occurs after IVT. Successful management of AD-related acute brain infarction with hypofibrinogenemia after IVT has not been reported previously. CASE REPORT: An 84-year-old woman developed sudden left limb weakness and aphasia for almost 4 h. Alteplase was administered intravenously immediately after cerebral hemorrhage was ruled out by emergent head computed tomography (CT). An anomaly suspected to be AD was detected during subsequent routine chest CT, which was confirmed by CT angiography to be a thoracoabdominal aortic dissecting aneurysm (DeBakey type I). Severe hypofibrinogenemia was also noted. After effective blood pressure control, intramuscular injection of vitamin K, and rehydration therapy, her brain cell metabolism improved, hemiplegia improved slightly, and hypofibrinogenemia recovered gradually. The patient's cerebral hemorrhage did not progress, there was no chest pain or no aggravation of hemiplegia, and the fibrinogen level gradually returned to normal. The condition was stable during hospitalization. At 1.5 months after discharge, the patient showed minimal change in condition. CONCLUSION: The symptoms of AD may be nonspecific and latent. IVT may be allowed to perform for some patients with AD related ischemical stroke, And IVT can improve the neural symptoms of AD-related ischemic stroke, but close monitoring is needed to avoid aneurysm rupture. Fibrinogen levels should also be monitored periodically after IVT for early detection of hypofibrinogenemia.

Beijing Friendship Hospital Osteoporosis Self-Assessment Tool for Elderly Male (BFH-OSTM) vs Fracture Risk Assessment Tool (FRAX) for identifying painful new osteoporotic vertebral fractures in older Chinese men: a cross-sectional study.

BACKGROUND: To compare the validation of four tools for identifying painful new osteoporotic vertebral compression fractures (PNOVCFs) in older Chinese men: bone mineral density (BMD), Asian osteoporosis self-assessment tool (OSTA), World Health Organization fracture risk assessment tool (FRAX) (without BMD) and Beijing Friendship Hospital Osteoporosis Self-Assessment Tool (BFH-OSTM). METHODS: A cross sectional study was conducted from 2013 to 2019. A total of 846 men aged ≥50 were included and were divided into two groups: Fracture Group (patients with PNOVCFs underwent percutaneous vertebroplasty surgery) and Non-Fracture Group (community dwelled subjects for healthy examination). All subjects accepted a dual-energy X-ray BMD test and a structured questionnaire. The results of BMD, OSTA, FRAX and BFH-OSTM scores were assessed and receiver-operating characteristic (ROC) curves were generated to compare the validity of four tools for identifying PNOVCFs. Optimal cutoff points, sensitivity, specificity, and areas under the ROC curves (AUCs) were determined. RESULTS: There were significant differences including BMD T score (femoral neck, total hip and L1-L4), OSTA, FRAX and BFH-OSTM scores between Fracture group and Non-fracture group. Compared to BMD and OSTA, BFH-OSTM and FRAX had better predictive value, the sensitivity, specificity and AUC value are 0.841, 81.29%, 70.67% and 0.796, 74.85%, 78.52%, respectively. Compared with FRAX, the BFH-OSTM has a better AUC value. CONCLUSIONS: Both BFH-OSTM and FRAX can be used to identify POVCFs, However, BFH-OSTM model may be a more simple and effective tool to identify the risk of POVCFs in Chinese elderly men.

Diagnosis and surgical treatment of primary isolated aggressive lumbar myeloid sarcoma: a rare case report and review of the literatures.

BACKGROUND: Myeloid sarcoma is a rare, extramedullary, solid tumor derived from immature myeloid cell precursors. It is most frequently accompanied by acute myelogenous leukemia, though infrequently found in non-acute myelogenous leukemia patients. The tumor may involve any part of the body, but the lumbar spine is seldom involved. The present case study aims to understand the diagnosis and surgical treatment of a rare primary isolated myeloid sarcoma of the lumbar spine causing aggressive spinal cord compression in a non-acute myelogenous leukemia patient. CASE PRESENTATION: A 29-year-old man complained of an aggressive radiating pain to the lower extremities and moderate dysuria with a Visual Analogue Scale score that gradually increased from 3 to 8. Lumbar enhanced magnetic resonance imaging and computed tomography revealed a lumbar canal lesion at lumbar spine L2 to L4 with spinal cord compression. A whole body bone scan with fused single photon emission computed tomography/computed tomography demonstrated abnormal 99mTc-methylene diphosphonate accumulation in the L3 lamina and spinous process. No evidence of infection or hematology disease was observed in laboratory tests. Due to rapid progression of the symptoms and lack of a clear diagnosis, decompression surgery was performed immediately. During the operation, an approximately 6.0 × 2.5 × 1.2 cm monolithic, fusiform, soft mass in the epidural space and associated lesion tissues were completely resected. The radiating pain was relieved immediately and the dysuria disappeared within 1 week. Intraoperative pathological frozen section analysis revealed a hematopoietic malignant tumor and postoperative immunohistochemistry examination confirmed the diagnosis of myeloid sarcoma. CONCLUSIONS: The primary isolated aggressive lumbar myeloid sarcoma is rarely seen, the specific symptoms and related medical history are unclear. Surgery and hematological treatment are effective for understanding and recognizing this rare tumor.

Non-linear dose-response relation between urinary levels of nicotine and its metabolites and cognitive impairment among an elderly population in China.

BACKGROUND: Active smoking and exposure to environmental tobacco smoke may be related to cognitive function decline. We assessed the associations of urinary levels of nicotine and its metabolites with cognitive function. METHODS: A total of 553 elder adults at high risk of cognitive impairment and 2212 gender- and age-matched individuals at low risk of cognitive impairment were selected at a ratio of 1: 4 from the remained individuals (n = 6771) who completed the baseline survey of the Shenzhen Ageing-Related Disorder Cohort, after excluding those with either Alzheimer's disease, Parkinson's syndrome or stroke as well as those with missing data on variables (including active and passive smoking status, Mini-Cog score). Urinary levels of nicotine and its metabolites and cognitive function for all individuals were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) and assessed using the Mini-Cog test, respectively. Associations of urinary levels of nicotine and its metabolites with cognitive function were analyzed by conditional logistic regression models. RESULTS: Individuals in the highest tertile of urinary OHCotGluc (OR: 1.52, 95%CI: 1.19-1.93) or NNO (OR: 1.50, 95%CI: 1.16-1.93) levels as well as in the second tertile of urinary ∑Nic level (OR: 1.43, 95%CI: 1.13-1.82) were at higher risk of cognitive impairment compared with those in the corresponding lowest tertile. Restricted cubic spline models revealed the non-linear dose-response relationships between urinary levels of OHCotGluc, NNO or ∑Nic and the risk of cognitive impairment. CONCLUSIONS: Urinary levels of OHCotGluc, NNO or ∑Nic exhibited a non-linear dose-response relationship with cognitive function in the urban elderly.

Rapid human-derived iPSC osteogenesis combined with three-dimensionally printed Ti6Al4V scaffolds for the repair of bone defects.

Human-induced pluripotent stem cells (iPSCs) are an alternative source of mesenchymal stem cells used for bone regeneration. However, the current osteogenically induced methods for iPSCs are slow and complex. We have used retinoic acid (RA) to induce osteogenic iPSCs within 10 days and assess whether a rapid differentiation could improve the osteogenic potential of the three-dimensionally printed Ti6Al4V (3DTi) scaffolds. First, the osteogenic differentiation of iPSCs was induced with RA, and the osteogenic potential of iPSCs was evaluated using standard assays. In addition, a 5-mm mandibular bone defect was generated in rats and was repaired with 3DTi scaffolds that were seeded with iPSC-induced osteoblasts. The capacity of seeded scaffolds for the enhancement of bone regeneration in vivo was assessed. Finally, we tested the potential mechanisms of RA-dependent iPSC bone induction and its effect on the Wnt/ß-catenin pathway. The results showed that iPSCs could form osteocytes within 10 days. Animal experiments confirmed that rapid osteo-induced iPSCs could enhance the bone regeneration and osteointegration capacity of the 3DTi scaffolds. Mechanistically, RA could activate the AKT/GSK3ß/ß-catenin pathway during the process of iPSCs osteogenesis. The rapid osteoinduction of iPSCs combined with 3DTi scaffolds is a safe, effective, and reproducible method for repairing mandibular bone defects.

A rare lumbar pyogenic spondylodiscitis caused by staphylococcus caprae with initial misdiagnosis: case report and literature review.

BACKGROUND: Staphylococcus caprae (Sc) is an uncommon causative organism for human. Lumbar pyogenic spondylodiscitis (LPS) of Sc is extremely rare and only a few cases have been reported. As far as we know, there is no specific literature on the diagnosis and treatment for LPS of Sc with L5 nerve root irritation. CASE PRESENTATION: A 65-year-old male patient complained of chronic low back pain for 10 years, acute worsening with radiating pain to left lower extremity over a month. Physical examination revealed tenderness point on his low back, 3/5 dorsiflexor strength in his left 1st toe and decreased sensation of pin prick over the left lateral shank and medial dorsal foot. The individual was initially misdiagnosed with lumbar disc herniation (LDH) without further examination in outpatient, which was then found to be LPS of Sc with L5 nerve root irritation after admission to our hospital. Magnetic resonance images (MRI) of lumbar spine exhibited inflammation signal at L4-L5 level of the vertebral body and disc with hypointense on T1-weighted images (T1-WI) and hyperintense on T2-weighted images (T2-WI). The causative organism was confirmed by the culture of irrigation fluid obtained from L5 vertebrae by needle puncture. After systemic conservative treatment including using sensitive antimicrobial agents and immobilization, the rare infection was finally cured. The patient also showed a satisfactory recovery during the 36-month follow-up period. CONCLUSIONS: Confirming the diagnosis and identifying the causative organism as soon as possible is the key point for the treatment of LPS. LPS of Sc causing nerve root irritation is rare but curable with early diagnosis and proper therapy. The culture of irrigation fluid obtained from vertebrae by needle puncture may be an effective and sensitive attempt for potential infection of spine to identify the causative organism at early stage of the disease.

An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED.

Polycomb repressive complex 2 (PRC2) consists of three core subunits, EZH2, EED and SUZ12, and plays pivotal roles in transcriptional regulation. The catalytic subunit EZH2 methylates histone H3 lysine 27 (H3K27), and its activity is further enhanced by the binding of EED to trimethylated H3K27 (H3K27me3). Small-molecule inhibitors that compete with the cofactor S-adenosylmethionine (SAM) have been reported. Here we report the discovery of EED226, a potent and selective PRC2 inhibitor that directly binds to the H3K27me3 binding pocket of EED. EED226 induces a conformational change upon binding EED, leading to loss of PRC2 activity. EED226 shows similar activity to SAM-competitive inhibitors in blocking H3K27 methylation of PRC2 target genes and inducing regression of human lymphoma xenograft tumors. Interestingly, EED226 also effectively inhibits PRC2 containing a mutant EZH2 protein resistant to SAM-competitive inhibitors. Together, we show that EED226 inhibits PRC2 activity via an allosteric mechanism and offers an opportunity for treatment of PRC2-dependent cancers.

Comparison of clinical outcomes of expansive open-door laminoplasty with unilateral or bilateral fixation and fusion for treating cervical spondylotic myelopathy: a multi-center prospective study.

BACKGROUND: The present study evaluated the clinical outcomes and safety of expansive open-door laminoplasty, when securing with C4 - C6 lateral mass screw and fusion. METHODS: A total of 110 patients with cervical spondylotic myelopathy (CSM) were enrolled. There were 88 male and 22 female, with mean age at 60.55 ± 10.95 years. All of the patients underwent expansive open-door laminoplasty with unilateral or bilateral C4-6 lateral mass screws fixation and fusion. Clinical data, including age, gender, operation-related information, pre- and post-operation Japanese Orthopedic Association (JOA) scores, and cervical curvatures were collected. RESULTS: The mean follow-up time of the cohort was 13.61 ± 9.53 months. Among the 110 patients, 33 of them were allocated to Unilateral group, and 77 of them were in Bilateral group. The mean JOA score of the 110 patients before surgery was 10.07 ± 2.39, and the score was improved significantly to 12.85 ± 2.45 after surgery. There were no reported cases of neurological deterioration or symptom worsening. Patients in both the Unilateral group and Bilateral groups had significant improvement of JOA scores. Among all patients, the most frequently observed complications were axial symptoms (n = 7). The average preoperative cervical curvature among all patients was 15.17 ± 5.26, and the post-surgery curvature was 14.41 ± 4.29. Similar observations were found between Unilateral and Bilateral groups. CONCLUSION: The modified surgical approach provided satisfactory clinical outcome in patients with CSM. The unilateral and bilateral fixation appeared to provide similar outcomes, in terms of cervical curvature maintenance and improvement of clinical symptoms. However, the examination of the exact differences between the two fixation methods await further biomechanical studies.

"Targeted Percutaneous Vertebroplasty" Versus Traditional Percutaneous Vertebroplasty for Osteoporotic Vertebral Compression Fracture.

Objective. In this randomized, nonblinded, controlled study, the feasibility and precision of "targeted percutaneous vertebroplasty" ("targeted PVP") for osteoporotic vertebral compression fracture (OVCF) was evaluated. Methods. A total of 42 patients, aged 50 to 87 years, with OVCF were randomly divided into 2 groups: A and B. Group A underwent "targeted PVP," and group B underwent traditional PVP with the guidance of C-arm fluoroscopy. Fluoroscopy times for skin puncture points (FTSPP), total radiation doses (TRD), total fluoroscopy times (TFT), and operation time were set as the main evaluation indicators. Results. FTSPP (1.52 ± 0.51 in group A vs 6.62 ± 2.58 in group B, U < .001), TRD (6.26 ± 1.51 in group A vs 11.32 ± 4.21 in group B, P < .001), TFT (16.57 ± 2.79 in group A vs 26.05 ± 6.18 in group B, P < .001), and operation time (20.05 ± 3.38 in group A vs 25.43 ±5.11 in group B, U < .001) were statistically different in the 2 groups. The incidence of cement leakage that occurred in group A (1/21, 4.76%) was significantly less than that in group B (9/21, 42.9%, P < 0.05). Conclusions. "Targeted PVP" may achieve (1) less skin positioning fluoroscopy times, less total fluoroscopy times and dose, shorter operation time, which is more precise than traditional PVP; (2) less incidence of cement leakage; and (3) visualization of the fractured vertebra, which is probably more valuable for the treatment of complicated OVCF patients.

SETDB1 modulates PRC2 activity at developmental genes independently of H3K9 trimethylation in mouse ES cells.

SETDB1, a histone methyltransferase responsible for methylation of histone H3 lysine 9 (H3K9), is involved in maintenance of embryonic stem (ES) cells and early embryonic development of the mouse. However, how SETDB1 regulates gene expression during development is largely unknown. Here, we characterized genome-wide SETDB1 binding and H3K9 trimethylation (H3K9me3) profiles in mouse ES cells and uncovered two distinct classes of SETDB1 binding sites, termed solo and ensemble peaks. The solo peaks were devoid of H3K9me3 and enriched near developmental regulators while the ensemble peaks were associated with H3K9me3. A subset of the SETDB1 solo peaks, particularly those near neural development-related genes, was found to be associated with Polycomb Repressive Complex 2 (PRC2) as well as PRC2-interacting proteins JARID2 and MTF2. Genetic deletion of Setdb1 reduced EZH2 binding as well as histone 3 lysine 27 (H3K27) trimethylation level at SETDB1 solo peaks and facilitated neural differentiation. Furthermore, we found that H3K27me3 inhibits SETDB1 methyltransferase activity. The currently identified reciprocal action between SETDB1 and PRC2 reveals a novel mechanism underlying ES cell pluripotency and differentiation regulation.

Berberine Protects Secondary Injury in Mice with Traumatic Brain Injury Through Anti-oxidative and Anti-inflammatory Modulation.

Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide. Novel and effective therapy is needed to prevent the secondary spread of damage beyond the initial injury. The aim of this study was to investigate whether berberine has a neuroprotective effect on secondary injury post-TBI, and to explore its potential mechanism in this protection. The mice were randomly divided into Sham-saline, TBI-saline and TBI-Berberine (50 mg/kg). TBI was induced by Feeney's weight-drop technique. Saline or berberine was administered via oral gavage starting 1 h post-TBI and continuously for 21 days. Motor coordination, spatial learning and memory were assessed using beam-walking test and Morris water maze test, respectively. Brain sections were processed for lesion volume assessment, and expression of neuronal nuclei (NeuN), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), 8-hydroxy-2-deoxyguanosine (8-OHdG), ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) were detected via immunohistochemistry and immunofluorescence. There were statistically significant improvement in motor coordination, spatial learning and memory in the TBI-Berberine group, compared to the TBI-saline group. Treatment with berberine significantly reduced cortical lesion volume, neuronal loss, COX-2, iNOS and 8-OHdG expression in both the cortical lesion border zone (LBZ) and ipsilateral hippocampal CA1 region (CA1), compared to TBI-saline. Berberine treatment also significantly decreased Iba1- and GFAP-positive cell number in both the cortical LBZ and ipsilateral CA1, relative to saline controls. These results indicated that berberine exerted neuroprotective effects on secondary injury in mice with TBI probably through anti-oxidative and anti-inflammatory properties.

Potential roles of microRNAs and their target genes in human multiple myeloma.

OBJECTIVES: The etiology of multiple myeloma (MM) is unknown and it remains incurable. We sought to elucidate the mechanisms underlying miRNAs involvement in MM pathogenesis. METHODS: Public mRNA and miRNA expression datasets for MM were collected from the Gene Expression Omnibus database. By integrated bioinformatics analysis, the expression signatures were identified and the miRNA-mRNA interaction network was constructed. The potential functions of target genes were then explored by functional enrichment analysis. RESULTS: Totally, 839 differentially expressed mRNAs and six differentially expressed miRNAs were identified. The context of miRNAs-mediated genes regulatory network consisted of 288 possible miRNA-mRNA target pairs. The hub miRNA was hsa-miR-92a, which can serve as the indicator for MM disease status. Another miRNA, hsa-miR-148a, could be useful for prognosis of MM. Functional annotation revealed that the miRNA targets may play important roles in viral infection and proteasome. Moreover, miRNA targets may be involved in renal cell carcinoma and other nervous system disease such as Huntington's disease, Alzheimer's disease and Parkinson's disease, which may be subsequent complications of MM. CONCLUSIONS: Infections could be a leading cause for the morbidity of MM patients. The crucial protein degradation machinery may be essential in the pathogenesis of MM.

[Effects of posterior lumbar spinal fusion on the stability of unstable lumbar segment and biomechanical properties of adjacent segments: a finite element study].

OBJECTIVE: To explore the effects of posterolateral lumbar fusion (PLF) and posterior lumbar interbody fusion (PLIF) on the stability of postoperative unstable single lumbar segment and the biomechanical alterations of the adjacent segments. METHODS: A finite element model of L3-S1 segments with a single segmental degeneration at the L4-5 level was established, and the model of L4-5 segmental instability after posterior laminectomy and facetectomy was also established, in which laminar and interior 2/3 area of bilateral facet joints were resected. Physical loads were applied to the models and the changes of the range of motion (ROM) at L4-5 level in different models were recorded at the condition of flexion, extension, lateral bending and rotation. PLF and PLIF were performed on postoperative unstable model respectively, the changes of the ROM at L4-5 level, the ROM and the stress on the adjacent discs in different models were recorded. RESULTS: Compared to the unstable model, the L4-5 segmental stability was restored after PLF or PLIF. The ROMs of L3-4 and L5-S1 levels were similar to the preoperative unstable model. The stress on adjacent discs (L3-4 and L5-S1) was increased significantly, and maximum stress distribution changed and concentrated in the anterior annulus fiber in the two fusion models. There was no significant difference of the maximum stress on adjacent discs between PLF and PLIF models [(1.056 ± 0.061) mPa vs (1.070 ± 0.075) mPa; (1.147 ± 0.055) mPa vs (1.162 ± 0.075)mPa, P>0.05]. CONCLUSIONS: Lumbar segmental stability after posterior laminectomy and facetectomy can be recovered by both PLF and PLIF. Both PLF and PLIF may increase the possibility of adjacent segment degeneration because of the augmentation of maximum stress on adjacent discs.

[Investigation of osteoporosis prevalence and osteoporosis-related clinical risk factors among healthy elderly male].

OBJECTIVE: To investigate the osteoporosis prevalence and osteoporosis-related clinical risk factors among healthy elderly male. METHODS: A cross-sectional study was conducted from January 2014 to October 2014. Healthy elderly male aged 50 and above from Beijing WangZuo Community who had completed the questionnaire we made were enrolled in this study and accepted bone mineral density (BMD) testing by dual energy X-ray absorptiometry. Subjects were classified as the osteoporosis group (OP group) and the non-osteoporosis group (Non-OP group) according to the WHO criteria, of which osteoporosis was defined arbitrarily when any T-score was -2.5 standard deviations or less at femoral neck, total hip or lumbar spine (L1-4). The clinical risk factors of each subject including age, body weight, Body Mass Index (BMI), previous fragility fracture history, smoking, alcohol abuse, glucocorticoid therapy and other capable clinical risk factors were collected and compared in OP group and Non-OP group. RESULTS: In the 346 cases of elderly healthy men, 18.5% had osteoporosis, 55.5% had osteopenia and 26.0% were normal. Femoral neck's and total hip's BMD level decreased with increasing age. However, the trend was not found at lumbar spine site. There appeared to be a significant difference in BMD standard between lumbar vertebral and total hip when compared with age-matched cohorts (P<0.05). Weight, BMI, previous fragility fracture history and smoking were found significant differences between OP group and Non-OP group (P<0.05). CONCLUSIONS: The prevalence of osteoporosis in healthy older men should not be ignored. Low BMI and weight, previous fragility fracture history and smoking history were clinical risk factors of OP in this population.

[Association of body mass index and male primary osteoporosis].

OBJECTIVE: To explore the association between body mass index (BMI) and male primary osteoporosis (OP) in a Chinese Han population. METHODS: The association of BMI with OP was assessed in 276 Chinese healthy aged males for physical examination. They were classified into OP, osteopenia and normal groups according to the World Health Organization (WHO) criteria, i.e. OP was defined arbitrarily when any T-score was -2.5 standard deviations or less at femoral neck, total hip or lumbar spine (L1-4) site. We also classified the subjects as different BMI groups of low weight, normal weight, overweight and obesity. The prevalence of OP was compared among different BMI groups. We determined the sensitivity, specificity and area under the curve of receiver operating characteristic (ROC) for validating the valuation of BMI to predict male primary OP. RESULTS: Among them, 6/12 had OP in the low weight group, 17.36% (21/121) in the normal group and 12.59% (18/143) in the overweight and obesity group. And the difference was significant. The analysis of ROC curve showed that BMI was of limited value in predicting OP (P > 0.05). CONCLUSION: BMI has a positive correlation with male OP. The value of BMI is limited for predicting OP in males. And the relevant factors associated with male OP should to be further studied.