lncRNA HHIP-AS1/HHIP modulates osteogenic differentiation of BM-MSCs by regulating Hedgehog signaling pathway.

BACKGROUND: lncRNA, a type of non-coding RNA, plays an important role in the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs). In this study, lncRNA and mRNA microarrays were performed to study the change of gene expression during osteogenic differentiation of BM-MSCs. We focused on Hedgehog interacting protein (HHIP), because HHIP mRNA and lncRNA HHIP-AS1 were gradually down-regulated on days 0, 7, and 14 during osteogenic differentiation. In addition, the gene coding lncRNA HHIP-AS1 is located on the anti-sense of Hhip gene, implying the potential interaction between lncRNA HHIP-AS1 and HHIP mRNA. METHODS: BM-MSCs with over-expressed or silenced lncRNA HHIP-AS1 were constructed to explore the biological role of HHIP-AS1 in osteogenic differentiation. BM-MSCs were lysed to determine the alkaline phosphatase activity. Fluorescence in situ hybridization and immunofluorescence were performed to analyze HHIP-AS1, HHIP, RUNX2 and osteocalcin. RESULTS: Overexpression of lncRNA HHIP-AS1 increased HHIP expression, which suppressed Hedgehog signaling pathway, as indicated by the reduction of SMO, Gli1 and Gli2. The suppression of Hedgehog signal was associated with the inhibited osteogenesis. HHIP knockdown abolished the suppression of osteogenesis induced by lncRNA HHIP-AS1 overexpression. Through binding to HHIP mRNA, lncRNA HHIP-AS1 recruited ELAVL1 to HHIP mRNA, whereby increasing the mRNA stability and the protein level. CONCLUSIONS: This study revealed that down-regulation of HHIP due to lncRNA HHIP-AS1 reduction promoted the osteogenic differentiation of BM-MSCs though removing the suppression of Hedgehog signal.

Meta-Analysis on the Anesthetic Effects of Remifentanil plus Dexmedetomidine versus Remifentanil Alone in Cardiac Surgery.

In this study, we performed a meta-analysis to investigate the anesthesia effects of remifentanil plus dexmedetomidine versus remifentanil alone in cardiac surgery. Literature search was performed on PubMed, Web of Science, Embase, China Knowledge Infrastructure, Wanfang Data, and other databases for relevant literature published in English or Chinese before October 2021. A total of 17 studies, consisting of 1350 patients, were included in this study. Of these, 10 studies showed that remifentanil plus dexmedetomidine had a good anesthesia effect in cardiac surgery (OR = 3.61, 95% CI: 1.73, 7.52, P < 0.001), and 8 studies showed that the Ramsay score test of anesthesia (SMD = 0.88; 95% CI: -0.77, 2.53; P < 0.001) in the experimental group was better than that in the control group. In addition, changes in the hemodynamic heart rate (SMD = -0.74; 95% CI: -1.41, -0.07; P < 0.001) and mean arterial pressure (SMD = -0.18; 95% CI: -0.72, 0.36; P < 0.001) of the two groups of anesthesia were counted in 17 studies, which also showed that the anesthesia effect of remifentanil plus dexmedetomidine was good. Thus, remifentanil plus dexmedetomidine may be a more promising option for cardiac surgery anesthesia than remifentanil alone.

RP11-867G2.8 promotes EMT and chordoma malignant phenotypes by enhancing FUT4 mRNA stability and translation.

Chordoma is a rare bone tumor, and the recurrence rate of chordoma is high, the treatment is difficult, and the prognosis is poor. Therefore, it is of great significance to find key target genes for the treatment of chordoma. Microarray was used to analyze the significant gene associated with chordoma. Western blot and RT-PCR were used to detect protein and mRNA expression levels of RP11-867G2.8 and FUT4. Fluorescence in situ hybridization (FISH) assay was used to locate the position of RP11-867G2.8 in chordoma cells. MTT assay, colony formation assay, transwell assay and Xenograft Mouse Model were used to clarify the function of RP11-867G2.8 and FUT4. RNA pull-down, RNA immunoprecipitation, RNA stability assay and polysome profiling analysis were used to clarify the relationship between RP11-867G2.8 and FUT4. We found that RP11-867G2.8 is highly expressed in chordoma tissues and cells, and RP11-867G2.8 overexpression promotes the malignant biological behavior of chordoma cells. RP11-867G2.8 overexpression alters the expression pattern of genes modulating signaling pathway. FUT4 is accumulated in chordoma tissues, and RP11-867G2.8 is antisense RNA of FUT4. RP11-867G2.8 can bind to FUT4 mRNA, increasing FUT4 mRNA stability and facilitating translation of FUT4. RP11-867G2.8 binds to EIF4B and PABPC1, which increases the translation of FUT4. Further studies found that FUT4 silence counteracts the effect of RP11-867G2.8 in vivo and in vitro. Our results suggest that RP11-867G2.8 promotes the development and progression of chordoma by up-regulating the expression of FUT4.

May Measurement Month 2019: an analysis of blood pressure screening results from China.

To report the blood pressure (BP) data obtained in the May Measurement Month (MMM) 2019 in China. Study participants were recruited if ≥18 years of age and had ideally not had their BP measured for ≥1 year. BP was measured three times consecutively with a 1-min interval in the sitting position, using a validated electronic BP monitor. Trained volunteer investigators administered a questionnaire to collect information on lifestyle, medical history, and use of medications. The measurement was performed in 238 387 participants in 250 sites across 31 China provinces. The majority of screening took place in hospitals or clinics (78.7%), with 17.1% in outdoor public areas and 4.2% in other settings. The study participants included 127 853 women (53.6%) and had a mean (±SD) age of 48.9 ± 16.2 years. The mean (of readings two and three) systolic/diastolic BP was 121.8/73.8 mmHg. In all hypertensive patients (n = 66 181, 27.8%), the awareness, treatment, and control rates of hypertension were 51.5%, 48.4%, and 29.1%, respectively. Linear regression models showed differences in systolic and diastolic BP according to sex and age and several other major characteristics, such as previous stroke, myocardial infarction, and diabetes mellitus, antihypertensive medication use and known hypertension, previous hypertension in pregnancy and current pregnancy, alcohol intake and current smoking, and body mass index. The MMM 2019 campaign has been successful in measuring BP in a large member of participants in China.

Neutrophil extracellular traps exacerbate coagulation and endothelial damage in patients with essential hypertension and hyperhomocysteinemia.

Patients with essential hypertension (EH) and hyperhomocysteinemia (HHCY) suffer from more increased thrombotic events than those in EH alone. However, the underlying mechanisms for this effect are not well understood. This study hypothesized that neutrophil extracellular trap (NET) releasing may be triggered by HHCY in patients in EH, thereby predisposing them to a more hypercoagulable state. Using a modified-capture enzyme-linked immunosorbent assay (ELISA) method, we observed that cell-free DNA (CF-DNA) and myeloperoxidase DNA (MPO-DNA) in patients With EH and HHCY were significantly higher. The NET formation was also positively correlated with homocysteine levels, neutrophil-lymphocyte ratio (NLR), and hypercoagulable markers (thrombin-antithrombin complex, D-dimers). Furthermore, neutrophils from patients in EH with HHCY were found to be predisposed to amplified NET release when compared to patients in EH without HHCY or CTR. Coagulation function assays showed that NETs in patients With EH and HHCY resulted in a significantly increased ability to generate thrombin and fibrin than in those in EH without HHCY or CTR. These procoagulant effects of NETs in patients With EH and HHCY were markedly inhibited (approximately 70%) by the cleavage of NETs with DNase I. Isolated NETs from patients With EH and HHCY neutrophils also exerted a strong cytotoxic effect on endothelial cells (ECs), converted them to apoptosis. This study revealed a previously unrecognized association between the hypercoagulable state and neutrophils in patients With EH and HHCY. Therefore, blocking NETs may represent a new therapeutic objective for preventing thrombosis in these patients.

Quercetin prevents necroptosis of oligodendrocytes by inhibiting macrophages/microglia polarization to M1 phenotype after spinal cord injury in rats.

BACKGROUND: Oligodendrocytes (OLs) death after spinal cord injury (SCI) contributes to demyelination, even leading to a permanent neurological deficit. Besides apoptosis, our previous study demonstrated that OLs underwent receptor-interacting serine-threonine kinase 3(RIP3)/mixed lineage kinase domain-like protein (MLKL)-mediated necroptosis. Considering that necroptosis is always accompanied with pro-inflammatory response and quercetin has long been used as anti-inflammatory agent, in the present study we investigated whether quercetin could inhibit necroptosis of OLs and suppress the M1 macrophages/microglia-mediated immune response after SCI as well as the possible mechanism. METHODS: In this study, we applied quercetin, an important flavonoid component of various herbs, to treat rats with SCI and rats injected with saline were employed as the control group. Locomotor functional recovery was evaluated using Basso-Beattie-Bresnahan (BBB) scoring and rump-height Index (RHI) assay. In vivo, the necroptosis, apoptosis, and regeneration of OLs were detected by immunohistochemistry, 5'-bromo-2'-deoxyuridine (BrdU) incorporation. The loss of myelin and axons after SCI were evaluated by Luxol fast blue (LFB) staining, immunohistochemistry, and electron microscopic study. The polarization of macrophages/microglia after SCI and the underlying mechanisms were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. In vitro, the ATP and reactive oxygen species (ROS) level examination, propidium iodide (PI) labeling, and Western blotting were used to analyze the necroptosis of cultured OLs, while the signaling pathways-mediated polarization of cultured macrophages/microglia was detected by qRT-PCR and Western blotting. RESULTS: We demonstrated that quercetin treatment improved functional recovery in rats after SCI. We then found that quercetin significantly reduced necroptosis of OLs after SCI without influencing apoptosis and regeneration of OLs. Meanwhile, myelin loss and axon loss were also significantly reduced in quercetin-treated rats, as compared to SCI + saline control. Further, we revealed that quercetin could suppress macrophages/microglia polarized to M1 phenotype through inhibition of STAT1 and NF-κB pathway in vivo and in vitro, which contributes to the decreased necroptosis of OLs. CONCLUSIONS: Quercetin treatment alleviated necroptosis of OLs partially by inhibiting M1 macrophages/microglia polarization after SCI. Our findings suggest that necroptosis of OLs may be a potential therapeutic target for clinical SCI.

Posterolateral decompression, bone graft fusion, posterior instrumentation, and local continuous chemotherapy in the surgical treatment of thoracic spinal tuberculosis.

To investigate the clinical efficacy of surgical treatment for thoracic spinal tuberculosis with kyphosis deformity via posterolateral debridement, fusion, posterior instrumentation and local continuous chemotherapy. A total of 25 patients with thoracic tuberculosis received surgery by posterolateral decompression, fusion, posterior instrumentation, and postural drainage with local continuous chemotherapy between June 2009 and October 2011. The clinical outcomes was evaluated using statistical analysis about deformity correction, bone fusion, neurologic status, and the visual analog score (VAS) and erythrocyte sedimentation rate (ESR). All of 25 patients were followed up for 39.0 ±â€Š10.7 months (range, 24-60 months) postoperatively. There was no recurrence of tuberculosis, breakage and looseness of internal fixation. Bony fusion was achieved in all cases with 6.7 ±â€Š1.9 months. The values of ESR recovered to normal within 6 months postoperatively. All patients with neurological deficit had significant improvement at the final follow-up. The average preoperative Cobb angles were significantly decreased to 12.2 ±â€Š2.9° (range, 8-17°) postoperatively, and at final follow-up were 12.9 ±â€Š2.7°. Our results showed that single-stage posterolateral debridement fusion, posterior instrumentation and local continuous chemotherapy can be expected to yield satisfactory clinical and radiographic outcomes in patients with thoracic spinal tuberculosis.

The reasons and clinical treatments of postoperative relapse of Pott's disease.

Literature about postoperative relapse of Pott's disease is rare. Accordingly, the risk factors and clinical treatments for postoperative relapse of Pott's disease remain controversial. In order to evaluate the clinical outcomes of surgical treatment of postoperative Pott's disease relapse, and to investigate its optimal therapeutic procedures with respect to focal characteristics, we performed a retrospective review of clinical and radiographic data that were prospectively collected between July 2008 and May 2014 from 753 consecutive spinal tubercular patients including 67 patients who were diagnosed and treated as postoperative relapse of Pott's disease in our hospital. Apart from 9 patients being treated conservatively, the remaining 58 cases received surgery in our series. Specifically, 12 cases underwent anterior debridement, interbody fusion with instrumentation; 15 cases received posterior instrumentation anterior debridement, and bone grafting; 10 cases underwent posterior decompression, bone grafting, and instrumentation; 7 cases with debridement, 5 with debridement and sinus resection. Nine cases received percutaneous drainage and low-dose local continuous chemotherapy. Clinical outcomes before and after treatment were evaluated with statistical analysis based on hematologic and radiographic examinations, bone fusion, and neurologic status. Patients were followed-up for a mean of 39.2 ±â€Š8.2 months (range, 24-60 months). Postoperatively, the erythrocyte sedimentation rate (ESR) became normal within 4-6 months in all patients, and solid bone fusion was achieved within 8 months. Patients exhibited significant improvements in neurological deficits postoperatively, while the visual analog scale for pain showed significant improvements in all patients at final follow-up. The outcomes of follow-up showed that the reasons for postoperative relapse of Pott's disease were multiple. Individualized therapeutic methods should be chosen in accordance with the patient's general condition, recurrence focal characteristic, surgeon's experience, but above all is administration of appropriate chemotherapy.

Posterior surgical treatment of ankylosing spondylitis with spinal tuberculosis: A case series and long-term follow-up.

This retrospective cohort study aimed to evaluate the clinical outcomes of posterior surgical treatment of ankylosing spondylitis (AS) with spinal tuberculosis (STB). This was a retrospective study including 12 patients treated between January 2004 and April 2014 for AS with STB at our department. All patients underwent 1-stage posterior internal fixation, debridement, and bone fusion. The patients were evaluated based on the American Spinal Injury Association (ASIA), kyphotic Cobb angle, and the visual analog score (VAS). All patients were followed up for an average of 42.7 ±â€Š13.2 months after surgery and bone fusion was achieved 6.8 ±â€Š1.3 months. According to ASIA, 2 cases were rated as Grade D, 10 cases were Grade E at last follow-up. The average preoperative Cobb angle was 26.7 ±â€Š7.6° (range 15-36) and the average postoperative Cobb angle was 7.8 ±â€Š1.2° (range 6-9). The mean latest follow-up Cobb angle was 9.1 ±â€Š1.0° (range 6-10). Compared with the average preoperative Cobb angle, there were significant differences regarding the kyphotic Cobb angle measured postoperatively and at final follow-up (P < .05). The VAS significantly was considerably improved between the preoperative and the last clinical visits. These positive results demonstrate that 1-stage surgical treatment for AS with STB by posterior debridement, fusion, and instrumentation can be an effective and feasible treatment method for this specific condition. It should be noted that it is necessary to carry out antiosteoporosis treatment and perform long-segmental instrumentation in order to obtain spinal stabilization.

The clinical outcomes and surgical strategy for cervical spine tuberculosis: A retrospective study in 78 cases.

Literature on the treatment of cervical spinal tuberculosis (CSTB) is uncommon, the surgical approaches to cervical spinal tuberculosis were controversial. The aim of the study was to evaluate the clinical outcomes of 3 surgical techniques in CSTB patients, and to determine the most appropriate approach for CSTB patients. Between April 2006 and June 2012, we performed a retrospective review of clinical and radiographic data that were collected from 850 consecutive spinal tubercular patients, including 87 patients who were diagnosed and treated for CSTB in our hospital. Apart from 9 patients being treated conservatively, the remainder (78 cases) underwent surgery by anterior debridement, interbody fusion and instrumentation (A group), posterior instrumentation and anterior debridement, fusion and instrumentation in a single or two-stage operation (AP group), or posterior debridement, fusion and posterior instrumentation (P group). The patients were evaluated preoperatively and postoperatively on the basis of hematologic, radiographic examinations, and neurologic function. The 78 patients were followed up for a mean duration of 41.2 ±â€Š7.2 months (range, 24-65 months). Postoperatively, the preoperative erythrocyte sedimentation rate (ESR) value returned to normal within 3 to 6 months in all patients, and solid bone fusion was achieved in 3 to 8 months. The patients exhibited significant improvement in deformity and neurological deficit postoperatively, while the visual analog scale for pain showed significant improvement in all patients at the last follow up visit. The follow-up outcomes demonstrated that all 3 surgical methods were viable management options for CSTB. Individualized therapeutic strategies should be selected according to the patient's general condition, focal characteristics, and the surgeon's experience.

One-stage surgical management for lumber brucella spondylitis with anterior debridement, autogenous graft, and instrumentation.

Literature reporting on lumber brucella spondylitis (LBS) is rare, therefore, the purpose of this study was to evaluate the outcomes of one-stage surgical management for lumber brucella spondylitis by anterior debridement, autogenous grafts, and instrumentation. This was a retrospective cohort study including 16 patients with lumber brucella spondylitis by treated from January 2009 to October 2011 in our department. All cases underwent one-stage anterior internal fixation, debridement, and bone fusion; clinical and radiographic results were analyzed and compared. All patients were followed up for an average of 35.3 ±â€Š8.1 months (range, 24-48 months). Brucella spondylitis was completely cured in all patients with bone fusion achieved in 4.8 ±â€Š1.3 months. Visual analog scale (VAS) scores were significantly improved between the preoperative and last follow-up visit and neurological function classification showed significant improvement after surgical intervention. Preoperatively, the Cobb angle was 20.7 ±â€Š9.8°, and measured 8.1 ±â€Š1.3° at the last follow-up visit. The outcomes of follow-up demonstrated that one-stage surgical treatment with anterior debridement, fusion, and instrumentation can be an effective and feasible treatment method for lumber brucella spondylitis.

(­)­Epicatechin protects against myocardial ischemia­induced cardiac injury via activation of the PTEN/PI3K/AKT pathway.

Flavonol (­)­epicatechin (EPI) is primarily contained in green tea (Camellia sinensis) and cocoa beans (Theobroma cacao), and has been demonstrated to be beneficial for the health of the cardiovascular system. However, the effect and the underlying mechanism of EPI on myocardial ischemia induced cardiac injury has not yet been determined. Therefore, the present study aimed to detect whether EPI inhibited myocardial ischemia injury. An in vivo mouse myocardial ischemia model was induced by the ligation of left descending coronary artery for 7 days. EPI (1 mg/kg/day) was administrated 10 days prior to myocardial ischemia operation. The in vitro mouse myocardial ischemia model was induced by cultivating neonatal mouse cardiomyocytes under anoxia condition for 12 h. Cardiomyocytes were treated with EPI (5 µM) for 1 h and then incubated under anoxia conditions. Mouse hearts and cultured cardiomyocytes were used for hematoxylin­eosin, masson, ultrasonography, terminal dUTP nick end­labeling, immunofluorescence, western blotting and MTT assays. Results revealed that myocardial ischemia­induced mouse cardiac injury was significantly inhibited by EPI, as evidenced by decreased myocardial apoptosis, cardiac fibrosis and myocardial hypertrophy and improved cardiac function. In addition, it was confirmed that EPI serves a protective effect against myocardial ischemia via the phosphatase and tensin homolog (PTEN)/phosphoinositide 3­kinase (PI3K)/protein kinase B (AKT) signaling pathway, which was reversed by the PI3K inhibitor, LY294002. The protective role of EPI in myocardial apoptosis was further confirmed on mouse cardiomyocytes following anoxia treatment in vitro. In conclusion, the data suggested that EPI protects against myocardial ischemia induced cardiac injury through the PTEN/PI3K/AKT signaling pathway in vivo and in vitro, which may provide clinical therapeutic approaches and targets for cardiac ischemia injury.

Inhibitory effect of wild-type P53 gene transfer on graft coronary artery disease.

OBJECTIVE: The aim of the present study was to investigate the inhibitory effect of wild-type P53 gene transfer on graft coronary artery disease (GCAD) after heart transplantation and the underlying mechanisms. METHODS: A rat model of heterotopic heart transplantation was established using Wistar rats as donors and Sprague-Dawley (SD) rats as recipients. The donor hearts were collected and perfused, via the coronary artery, with 800 µl of recombinant adenovirus carrying the P53 gene (Ad-P53). Thirty minutes later, heart transplant was performed. At 5 d after the transplant surgery, the expression of the exogenous P53 gene and protein in the coronary artery tissues of the donor hearts was examined. At 28 d after the transplant surgery, tissues were collected from the transplanted hearts. The degree of coronary artery stenosis was examined, and apoptosis of the coronary artery smooth muscle cells in the donor hearts was analysed. In addition, histological changes in the vital organs of the recipient rats and the levels of serum biochemical indicators in the rats were also examined. RESULTS: The exogenous gene was successfully transferred into donor heart tissues and the coronary artery and was highly expressed. At 28 d after the transplant surgery, the ratio of tunica intima thickness to tunica media thickness (I/M) and the ratio of wall thickness to the lumen diameter of the coronary artery were decreased in the Ad-P53 group compared to those in the Ad-LacZ group and the control group (P < 0.05). A terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay revealed that the percentage of apoptotic coronary artery smooth muscle cells in the donor hearts was significantly increased in the Ad-P53 group compared to that in the Ad-LacZ group and the control group (P < 0.01). The wild-type P53 gene had no effect on the morphology and functions of the vital organs of the recipient rats. CONCLUSIONS: P53 gene transfer inhibits coronary artery intimal hyperplasia and reduces the degree of luminal stenosis in transplanted hearts. The inhibitory effect may be related to the wild-type P53 gene-induced apoptosis of vascular smooth muscle cells and inhibition of vascular smooth muscle cell proliferation. This approach is effective and safe and may have good prospects for clinical application.

Positive association between musclin and insulin resistance in obesity: evidence of a human study and an animal experiment.

BACKGROUND: Musclin is a novel skeletal muscle-derived secretory factor considered to be a potent regulator of the glucose metabolism and therefore may contribute to the pathogenesis of obesity and insulin resistance (IR). METHODS: To test this hypothesis, we examined the plasma musclin levels in overweight/obese subjects and lean controls. Rats on a high fat diet (HFD) were used as the annimal model of obesity. Radioimmunoassay and western blot were used to determine musclin levels in plasma and skeletal muscle. RESULTS: According to radioimmunoassays,the overweight/obese subjects exhibited elevated musclin plasma levels compared with the lean controls (89.49 ± 19.00 ng/L vs 80.39 ± 16.35 ng/L, P < 0.01). The musclin levels were positively correlated with triglyceride, fasting plasma glucose, and homeostasis model assessment of IR levels. These observations were confirmed with a high-fat diet(HFD) rat model. HFD rats also exhibited increased musclin immunoreactivity in plasma (P < 0.01) and in skeletal muscle (P < 0.05), as well as increased musclin mRNA levels in skeletal muscle (P < 0.01). Musclin incubation significantly inhibited muscles 3H-2-DG uptake in the normal diet(ND) group (P < 0.01). The protein expression of glucose transporter type 4 was significantly down regulated by 30% (P < 0.05) in the ND group after soleusmuscle was incubated with musclin compared with the control. Musclin incubation also increased the protein levels of glucose-regulated protein (GRP)78 and GRP94 by 146.8 and 54% (both P < 0.05), respectively, in ND rats. CONCLUSIONS: Our data support the hypothesis that musclin has a strong relationship with obesity-associated IR by impairing the glucose metabolism and, at least in part, through causing endoplasmic reticulum stress.

Increased circulating levels of musclin in newly diagnosed type 2 diabetic patients.

BACKGROUND: Musclin is a newly identified skeletal muscle-derived secretory factor, which has been recently characterized as a stimulator that induces insulin resistance in mice. However, the pathophysiological role of musclin in humans remains poorly understood. The aim of this study was to explore the potential correlations between musclin plasma levels and various metabolic parameters in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: In this hospital-based study, plasma samples were collected from the enrolled individuals, including 38 newly diagnosed, treatment-naive type 2 diabetes mellitus patients and 41 age- and gender-matched control subjects. Plasma musclin levels were examined by radioimmunoassay. RESULTS: Compared with the control group, musclin plasma levels were significantly higher in untreated type 2 diabetes mellitus patients. Musclin levels in the plasma of newly diagnosed type 2 diabetes mellitus patients were positively correlated with fasting plasma glucose, haemoglobin A1c, serum insulin, triglycerides and homeostasis model assessment of insulin resistance. Furthermore, multivariate logistic regression analysis showed that the level of musclin was associated with the presence of type 2 diabetes mellitus. Receiver operating characteristic curve analysis yielded an area under the curve for musclin of 0.718 in type 2 diabetes mellitus. CONCLUSION: The circulating concentration of musclin was significantly increased in type 2 diabetes mellitus patients. Our results suggest that musclin has a strong relationship with insulin resistance in type 2 diabetes mellitus.

Comparison of Three Surgical Approaches for Thoracic Spinal Tuberculosis in Adult: Minimum 5-Year Follow Up.

STUDY DESIGN: Retrospective study. OBJECTIVE: To assess the minimum 5-year follow up outcomes of the surgical management of adults with thoracic tuberculosis by comparing posterior only (PO), anterior only (AO), and combined posterior and anterior (AP) surgical approaches. SUMMARY OF BACKGROUND DATA: Surgeons use multiple methods to treat spinal tuberculosis, including an anterior, posterior, and combined anterior and posterior approach. However, there are a few reports comparing the mid- and long-term outcomes of these surgical methods. METHODS: The medical records for 184 patients treated for thoracic tuberculosis between January 2003 and November 2010 were retrospectively reviewed. Among them, 62 patients were treated with a single-stage posterior debridement and interbody fusion with instrumentation (Group A), 65 patients with posterior instrumentation, anterior debridement, and bone graft in a single or two-stage procedure (Group B), and 57 patients with anterior debridement and strut grafting with instrumentation (Group C). Operative time, blood loss, Visual Analog Scale for pain, complications, recovery of neurological function, Cobb angle, correction rate, and loss angle were compared among all groups. RESULTS: Groups A, B, and C were followed for 72.7 ±â€Š3.8 months, 74.3 ±â€Š4.2 months, and 73.6 ±â€Š4.5 months, respectively. The operative time, blood loss, and rate of complications for Group A were significantly less than Groups B and C (P < 0.05). The correction rate and loss angle were superior in Groups A and B compared with C, whereas the Visual Analog Scale for pain and fusion time showed no statistically significant difference among the groups (P > 0.05). CONCLUSION: For patients with thoracic tuberculosis, use of the AO approach should be limited. Although the AP approach produced satisfactory outcomes, it remains more traumatic. Therefore, the PO approach is recommended, not only because it achieves good results, but because it has reduced complications, operative time, and blood loss. LEVEL OF EVIDENCE: 3.

Cortistatin Improves Cardiac Function After Acute Myocardial Infarction in Rats by Suppressing Myocardial Apoptosis and Endoplasmic Reticulum Stress.

OBJECTIVES:: The endoplasmic reticulum (ER) stress-induced apoptotic pathway is associated with the development of acute myocardial infarction (AMI). Cortistatin (CST) is a novel bioactive peptide that inhibits apoptosis-related injury. Therefore, we investigated the cardioprotective effects and potential mechanisms of CST in a rat model of AMI. METHODS:: Male Wistar rats were randomly divided into sham, AMI, and AMI + CST groups. Cardiac function and the degree of infarction were evaluated by echocardiography, cardiac troponin I activity, and 2,3,5-triphenyl-2H-tetrazolium chloride staining after 7 days. The expression of CST, ER stress markers, and apoptotic markers was examined using immunohistochemistry and Western blotting. RESULTS:: Compared to the AMI group, the AMI + CST group exhibited markedly better cardiac function and a lower degree of infarction. Electron microscopy and terminal deoxynucleotidyl transferase dUTP nick end labeling confirmed that myocardial apoptosis occurred after AMI. Cortistatin treatment reduced the expression of caspase 3, cleaved caspase 3, and Bax (proapoptotic proteins) and promoted the expression of Bcl-2 (antiapoptotic protein). In addition, the reduced expression of glucose-regulated protein 94 (GRP94), glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding proteins homologous protein, and caspase 12 indicated that ER stress and the apoptotic pathway associated with ER stress were suppressed. CONCLUSIONS:: Exogenous CST has a notable cardioprotective effect after AMI in a rat model in that it improves cardiac function by suppressing ER stress and myocardial apoptosis.

Liraglutide attenuates the osteoblastic differentiation of MC3T3­E1 cells by modulating AMPK/mTOR signaling.

Liraglutide, a synthetic analogue of glucagon-like peptide­1, is utilized in the treatment of type 2 diabetes and obesity. Liraglutide has been previously demonstrated to prevent osteoblastic differentiation of human vascular smooth muscle cells, resulting in the slowing of arterial calcification, however, its effect on bone formation remains unclear. The present study investigated the effect of liraglutide on osteoblastic differentiation using Alizarin Red S staining, and examined the molecular mechanisms underlying the regulatory effect by western blot analysis. The present study demonstrated that protein expression levels of phosphorylated adenosine monophosphate­activated protein kinase (p­AMPK) were downregulated in MC3T3­E1 cells during osteoblastic differentiation in commercial osteogenic differentiation medium, whereas protein expression levels of transforming growth factor­ß (TGF­ß) and phosphorylated mammalian target of rapamycin (p­mTOR) increased. Liraglutide was subsequently demonstrated to dose­dependently attenuate the osteoblastic differentiation of MC3T3­E1 cells, to upregulate p­AMPK, and downregulate p­mTOR and TGF­ß protein expression levels. Treatment with an AMPK­specific inhibitor, Compound C, eradicated the effect of liraglutide on osteoblastic differentiation, and p­mTOR and TGF­ß downregulation. An mTOR activator, MHY1485, also abolished the inhibitory effect of liraglutide on osteoblastic differentiation, and resulted in p­mTOR and TGF­ß downregulation, but did not attenuate the liraglutide­induced increase in p­AMPK protein expression levels. The results of the present study demonstrate that liraglutide attenuates osteoblastic differentiation of MC3T3­E1 cells via modulation of AMPK/mTOR signaling. The present study revealed a novel function of liraglutide, which contributes to the understanding of its pharmacological and physiological effects in clinical settings.

MicroRNA-377 Mediates Cardiomyocyte Apoptosis Induced by Cyclosporin A.

Cyclosporin A (CsA) is a potent immunosuppressant that has wide clinical applications for autoimmune disorders and prevention of rejection in organ transplantation. However, its liver, kidney, and heart toxicity has limited its use. In this study, we investigated the mechanism by which CsA induced cardiomyocyte apoptosis. Through microarray analysis, we found that the expression of microRNA (miR)-377 was regulated by CsA. Ectopic overexpression of miR-377 led to increased apoptosis in cardiomyocytes, as evidenced by an increased number of apoptotic cells, increased levels of proapoptotic proteins, decreased levels of antiapoptotic proteins, and elevated caspase pathway activity. We also found that miR-377 was required for CsA-induced apoptosis, because inhibition of miR-377 expression markedly reduced the ability of CsA to induce cardiomyocyte apoptosis. In addition, we identified XIAP and NRP2 as direct targets for miR-377. The expression levels of these 2 antiapoptotic proteins were negatively regulated by miR-377, as well as by CsA both in vitro and in vivo. Our data suggested that CsA induced cardiomyocyte apoptosis through the miR-377-XIAP/NRP2 axis.

Comparison between the antero-posterior and posterior only approaches for treating thoracolumbar tuberculosis (T10-L2) with kyphosis in children: a minimum 3-year follow-up.

PURPOSE: There are few papers in the literature comparing outcomes between antero-posterior and posterior-only approaches for treating thoracolumbar tuberculosis (T10­L2) in children. METHODS: We performed a retrospective review of 47 children who were diagnosed and treated as thoracolumbar tuberculosis (T10­L2) in our department from January 2005 to June 2009. Forty-seven cases of thoracolumbar tuberculosis were treated by two different surgical approaches. All the cases were divided into two groups: 25 cases in group A underwent one-stage posterior debridement, transforaminal fusion, and instrumentation, and 22 cases in group B underwent anterior debridement, bone graft, and posterior instrumentation in a single- or two-stage procedure. Two approaches were compared in terms of average operative time, blood loss, hospitalizations, bony fusion, intraoperative and postoperative complications, the Oswestry disability index score, neurological status, and the angle of kyphosis. RESULTS: All 47 patients (24 M/23F), averaged 9.1 ± 2.6 years old (range 5 to 14 years), who were followed up for mean of 49.3 ± 8.6 months (range 36 to 65 months). Spinal tuberculosis (TB) was completely cured, and the grafted bones were fused in 9 months in all cases. It was obviously that the average operative time, blood loss, hospitalization, and complication rate of group A was less than those of group B. Good clinical outcomes were achieved in both groups. CONCLUSIONS: Both the antero-posterior and posterior approaches can effectively heal T10­L2 vertebral tuberculosis, but the average surgical time, blood loss, complications, and hospital stay following the posterior approach are prominently less than those following the antero-posterior approach. It might be a better surgical treatment for thoracic spinal tuberculosis in children with poor health status, especially for cases in early phase of bone destruction and/or mild and moderate kyphosis.