Naps and cardiovascular disease risk in different age and sex groups: evidence from a large community cohort.

STUDY OBJECTIVES: This study examined the relationship between naps and cardiovascular disease (CVD) events or death in different age and sex groups. METHODS: A total of 3069 participants stratified by age (<65, 65-74, and ≥75 years old) and sex, underwent Cox regression analysis to assess nap's impact on CVD risk. Restricted cubic spline plots (RCS) were used for dose-response relationships. RESULTS: Significant age-stratified interactions were found when exploring the associations between nap frequency or duration and CVD events (P interaction = 0.001, 0.036 respectively). Individuals younger than 65 years with higher nap frequency or longer nap duration had a significantly increased risk of CVD events (P < 0.001, P = 0.001 respectively). The age group of 65-74 years showed significant associations between CVD events and nap frequency or nap duration (P = 0.017, 0.016 respectively), together with nap duration and CVD deaths (P = 0.008). In the subgroup of females aged 65-74, significant associations were found between nap frequency or duration and CVD events (P = 0.006, 0.002 respectively). Nap frequency or duration was also significantly associated with CVD deaths (P =0.005, 0.010 respectively). CONCLUSIONS: This study underscores a noteworthy correlation between a higher frequency or longer duration of daytime nap and an increased susceptibility to CVD among individuals aged 65-74 years, particularly in females. However, further research is needed to better understand the underlying mechanisms.

Objective sleep characteristics and hypertension: a community-based cohort study.

Objective: The link between sleep quality and hypertension risk is well-established. However, research on the specific dose-relationship between objective sleep characteristics and hypertension incidence remains limited. This study aims to explore the dose-relationship association between objective sleep characteristics and hypertension incidence. Methods: A community-based prospective cohort study design was employed using data from the Sleep Heart Health Study (SHHS). A total of 2,460 individuals were included in the study, of which 780 had hypertension. Baseline personal characteristics and medical history were collected. Objective sleep characteristics were obtained through polysomnography (PSG). Multivariate logistic regression models were utilized for analysis. Restricted cubic splines (RCS) were used to examine dose-relationship associations. Results: After adjusting for covariates, the percentage of total sleep duration in stage 2 (N2%) was positively associated with hypertension incidence, while the N3% was negatively associated with hypertension incidence Odds ratio (OR) = 1.009, 95% confidence interval (CI) [1.001, 1.018], P = 0.037; OR = 0.987, 95% CI: [0.979, 0.995], P = 0.028, respectively. For every 10% increase in N2 sleep, the risk of developing hypertension increases by 9%, while a 3% decrease in N3 sleep corresponds to a 0.1% increase in the incidence of hypertension. In the subgroup of non-depression, a positive association between N2% and hypertension was significant statistically (OR = 1.012, 95%CI, 1.002, 1.021, P = 0.013, Pinteraction = 0.013). RCS demonstrated that the risk of developing hypertension was lower when N2% ranged from 38% to 58% and rapidly increased thereafter (P = 0.002, non-linear P = 0.040). The lowest risk for hypertension incidence risk of N3% occurring at 25%, and a significant increase below 15% or above 40% (P = 0.001, non-linear P = 0.008). Conclusions: There's a negative association between N3% and the incidence of hypertension, and a positive association between N2% and the incidence of hypertension, particularly among non-depression individuals. These associations exhibit strong non-linear dose-response relationships.

Dl-3-n-Butylphthalide Alleviates Secondary Brain Damage and Improves Working Memory After Stroke in Cynomolgus Monkeys.

BACKGROUND: Remote secondary neurodegeneration is associated with poststroke cognitive impairment (PSCI). Dl-3-n-butylphthalide (NBP) improves PSCI clinically. However, whether it ameliorates PSCI by alleviating secondary neurodegeneration remains uncertain. Nonhuman primates provide more relevant models than rodents for human stroke and PSCI. This study investigated the effects of NBP on PSCI and secondary neurodegeneration in cynomolgus monkeys after permanent left middle cerebral artery occlusion (MCAO). METHODS: Thirteen adult male cynomolgus monkeys were randomly assigned to sham (n=4), MCAO+placebo (n=5), and MCAO+NBP groups (n=4). The MCAO+placebo and MCAO+NBP groups received saline and NBP injections intravenously, respectively, starting at 6-hour postsurgery for 2 weeks, followed by soybean oil and NBP orally, respectively, for 10 weeks after MCAO. Infarct size was assessed at week 4 by magnetic resonance imaging. Working memory and executive function were evaluated dynamically using the delayed response task and object retrieval detour task, respectively. Neuron loss, glia proliferation, and neuroinflammation in the ipsilateral dorsal lateral prefrontal cortex, thalamus, and hippocampus were analyzed by immunostaining 12 weeks after MCAO. RESULTS: Infarcts were located in the left middle cerebral artery region, apart from the ipsilateral dorsal lateral prefrontal cortex, thalamus, or hippocampus, with no significant difference between the MCAO+placebo and MCAO+NBP group. Higher success in delayed response task was achieved at weeks 4, 8, and 12 after NBP compared with placebo treatments (P<0.05), but not in the object retrieval detour task (all P>0.05). More neurons and less microglia, astrocytes, CD68-positive microglia, tumor necrosis factor-α, and inducible NO synthase were observed in the ipsilateral dorsal lateral prefrontal cortex and thalamus after 12 weeks of NBP treatment (P<0.05), but not in the hippocampus (P>0.05). CONCLUSIONS: Our findings indicate that NBP improves working memory by alleviating remote secondary neurodegeneration and neuroinflammation in the ipsilateral dorsal lateral prefrontal cortex and thalamus after MCAO in cynomolgus monkeys.

Risk Factors and Prognostic Implications of New-Onset Paroxysmal Atrial Fibrillation in Patients Hospitalized with Intracerebral Hemorrhage.

Objective: We aimed to assess the prevalence and risk factors of new-onset paroxysmal atrial fibrillation (PAF) in patients hospitalized with ICH and determine whether the new-onset PAF had influenced functional outcomes. Methods: We analyzed a database of all consecutive patients with ICH from October 2013 to May 2022. Univariate and multivariable regression analyses were performed to identify risk factors for new-onset PAF in patients with ICH. Multivariate models were also constructed to assess whether the new-onset PAF was an independent predictor of poor functional outcome, as measured using the modified Rankin scale. Results: This study included 650 patients with ICH, among whom 24 patients had new-onset PAF. In the multivariable model, older age (OR per 10-y increase, 2.26 [95% CI, 1.52-3.35]; P<0.001), hematoma volume (OR per 10-mL increase, 1.80 [95% CI, 1.26-2.57]; P=0.001), and heart failure (OR, 21.77 [95% CI, 5.52-85.91]; P<0.001) were independent risk factors for new-onset PAF. In a sensitivity analysis restricted to 428 patients with N-terminal pro-B-type natriuretic peptide (NT-proBNP), older age, larger hematoma volume, heart failure, and increased NT-proBNP were associated with new-onset PAF. After adjusting for baseline variables, new-onset PAF was an independent predictor of poor functional outcome (OR, 10.35 [95% CI, 1.08-98.80]; P=0.042). Conclusion: Older age, larger hematoma volume, and heart failure were independent risk factors for new-onset PAF after ICH. Increased NT-proBNP is correlated with higher risks for new-onset PAF when their information is available at admission. Furthermore, new-onset PAF is a significant predictor of poor functional outcome.

Percutaneous screw fixation assisted by hollow pedicle finder for superior pubic ramus fractures.

BACKGROUND: Pubic ramus fracture was an injury of anterior pelvic ring, the anterior pelvic ring plays an important role in maintaining the stability of the pelvis. The purpose of this study was to investigate the effect and indication of percutaneous retrograde pubic screw fixation assisted by hollow pedicle finder for pubic ramus fractures. METHODS: The clinical data of 68 patients with pubic ramus fracture treated with cannulated screw from March 2008 to March 2020 were retrospectively analyzed. According to the surgical methods, they were divided into traditional surgery group (32 cases in group A, with traditional retrograde pubic screw fixation) and modified surgery group (36 cases in group B, with percutaneous retrograde pubic screw fixation assisted by hollow open circuit device). Operation time, blood loss, incision length, screw length and complications were recorded and compared between the two groups. On the second day after surgery, the maximum fracture displacement over plain radiographs, entrance radiographs and exit radiographs of the pelvis was evaluated according to Matta criteria to evaluate the postoperative fracture reduction. Majeed score was used to evaluate the hip function at 12 months after surgery. RESULTS: The operations were successfully completed in both groups. The operation time, blood loss and incision length in group B were significantly less than those in group A (P < 0.05). There was no significant difference in screw length between the two groups (t = 0.797, P = 0.431). All patients were followed up for 8-38 months (mean 21.8 months). There were no vascular and nerve injury, fracture of internal fixator, screw entry into joint cavity, fracture nonunion and other complications in both groups. The fracture healing time of the two groups was 23.1 ± 2.1 weeks in group A while 22.7 ± 2.1 weeks in group B, respectively, and there was no statistical difference in the fracture healing time between the two groups (P > 0.05). In group A, there were 3 cases of incision infection, 1 case of incision fat liquefaction and 2 cases of lower extremity deep venous thrombosis, and the complication rate was 18.8%. There was only 1 case of lower extremity deep vein thrombosis in group B, and the complication rate was 2.8%, which was significantly lower than that in group A. The fracture in one case after surgery was found to be displaced in group A and no fracture was found in group B. There was no significant difference between the two groups in Matta imaging evaluation on the next day after surgery and Majeed function evaluation at 12 months after surgery (P > 0.05). CONCLUSION: Percutaneous retrograde pubic ramus screw fixation assisted by hollow pedicle finder is effective in the treatment of pelvic pubic ramus fracture. It has the advantages of less incision, shorter operation time, less blood loss and lower incidence of complications compared with traditional methods. However, correct surgical indications should be required when we apply this surgical method.

Altered excitability of motor neuron pathways after stroke: more than upper motor neuron impairments.

BACKGROUND: Previous studies have suggested that impairment occurs in the lower motor neuron (LMN) pathway after stroke, but more research remains to be supported. OBJECTIVE: In this study, we tested the hypotheses: (1) both motor cortex and peripheral nerve pathways have decreased excitability and structural damage after stroke; (2) parameters of transcranial magnetic stimulation motor evoked potentials (TMS-MEP) can be used as predictors of motor function and stroke prognosis. METHODS: We studied five male cynomolgus monkeys with ischaemic stroke. TMS-MEP, cranial MRI, behavioural assessment, neurological scales and pathology were applied. RESULTS: Elevated resting motor threshold (RMT) (p<0.05), decreased TMS-MEP amplitudes (p<0.05) and negative RMT lateralisation were detected in both the affected motor cortex (AMC) and the paretic side median nerve (PMN) at 2 weeks poststroke. Disturbed structure and loose arrangement of myelin sheaths were observed in the PMN through H&E staining and LFB staining at 12 weeks poststroke. The primate Rankin Scale (used for assess the stroke prognosis) scores at 2-12 weeks after middle cerebral artery occlusion were [1, (1; 3)], [1, (1;2)], [1, (1; 1.5)] and [1, (1; 1.5)], respectively. The RMT and RMT lateralisation (AMC) were predictors of stroke prognosis, and the RMT lateralisation of PMN and latency of AMC were predictors of motor impairment. CONCLUSIONS: Both upper motor neuron (UMN) and LMN pathway excitability is reduced after stroke, and structural damage in median nerve 12 weeks after stroke occur. In addition, RMT and RMT lateralisation are predictors of stroke prognosis and motor impairment.

[Effectiveness analysis of medial buttress plate augmented hollow lag screws fixation in combination with sartorius pedicled iliac flap for the treatment of femoral neck fractures in young adults].

OBJECTIVE: To evaluate the effectiveness of medial buttress plate augmented hollow lag screws fixation in combination with sartorius pedicled iliac flap for the treatment of femoral neck fractures in young adults. METHODS: The clinical data of 11 young adult patients with femoral neck fractures between February 2013 and February 2019 were analyzed retrospectively. There were 7 males and 4 females with a mean age of 45 years (range, 32-58 years). Fractures were caused by falling from height in 6 cases, by traffic accident in 4 cases, and by sports injury in 1 case. There were 7 cases in the left hip and 4 cases in the right hip. The mean Pauwels angle was 64° (range, 55°-75°). All patients were treated by medial buttress plate augmented hollow lag screws fixation and sartorius pedicled iliac flap. The X-ray film of pelvis, lateral X-ray film of hip joint, CT scan and three-dimensional reconstruction of hip joint were taken after operation to assess fracture healing and position of the internal fixators. The postoperative hip function was evaluated according to the Harris score. RESULTS: All the incisions healed by first intention, and no complication such as incision infection and lateral femoral cutaneous nerve injury happened. Re-examination on the second day after operation showed that reduction and fixation of fractures was good. All patients were followed up 18-36 months (mean, 29 months). All fractures achieved bony union. The time of bony union was 16-23 weeks, with an average of 18.2 weeks. One patient (9.1%) got osteonecrosis of the femoral head (ONFH) at 30 months after operation. At last follow-up, Harris score was used to evaluate hip joint function, 9 cases were excellent, 1 case was good, 1 case was fair, and the excellent and good rate was 90.9%. CONCLUSION: Medial buttress plate augmented hollow lag screws fixation in combination with sartorius pedicled iliac flap for the treatment of femoral neck fractures in young adults has the advantage of strong biomechanical stability and can effectively improve the blood supply of femoral head and neck, which subsequently reduce the incidence of ONFH. However, the surgical indication should be fully considered.

Clinical outcomes of doubled-suture Nice knot augmented plate fixation in the treatment of comminuted midshaft clavicle fracture.

BACKGROUND: Free bone fragments were difficult to be fixed in many comminuted midshaft clavicle fractures, and the absence of cortical alignment in comminuted fractures had direct influence on the stability of fixation. This survey was performed to assess the efficacy of doubled-suture Nice knot augmented plate fixation in the treatment of comminuted midshaft clavicle fractures. METHODS: Between 2013 and 2018, all patients with comminuted midshaft clavicle fractures treated with doubled-suture Nice knot augmented plate fixation were retrospectively reviewed and included in this research. Demographic data of the patients, characteristics of the fractures, intraoperative parameters and follow-up data of the patients were evaluated and summarized. RESULTS: A total of 56 patients were included in this study. The mean follow-up time was 25.6 months (range, 12-60 months). The number of male patients was 38 (67.9 %) and of the female patients was 18 (32.1 %). The average age of all patients was 47.89 ± 16.5 years. The mean time of surgery was 85.6 ± 24.0 min. The average length of incision was 9.2 ± 1.9 cm. The number of doubled-suture Nice knot applied ranged from 1 to 5 knots. All the patients reached bone union after the treatment. There was no implant failure or neurovascular injury observed. And most of the patients showed good functional outcome. CONCLUSIONS: The doubled-suture Nice knot could provide reliable fixation for small bone fragments in comminuted clavicle fractures. Combination of the doubled-suture Nice knot and plate screws fixation was a safe and effective method in comminuted midshaft clavicle fractures treatment.

Aspirin Therapy in Cardiovascular Disease with Glucose-6-Phosphate Dehydrogenase Deficiency, Safe or Not?

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect, which may present as acute hemolysis, neonatal jaundice, or chronic hemolysis. Ingestion of fava beans, as well as infection and certain drugs, are the most typical causes of acute hemolysis in people with G6PD deficiency. Aspirin, the cornerstone in current therapies for the prevention of cardiovascular disease (CVD), is occasionally reported to induce acute hemolysis in G6PD-deficient individuals. G6PD deficiency is typically asymptomatic and many CVD patients with this enzyme defect start to take long-term aspirin therapy without G6PD activity examination; however, no consensus on the safety of aspirin in this population has been reached. A few studies have reported on this issue and produced contradictory results. In this review, we discuss the possible mechanisms of aspirin-induced hemolysis, and summarize clinical evidence regarding the safety of aspirin in subjects with G6PD deficiency.

The independent risks and specific biomarker of breast cancer-related ischemic stroke.

AIM: This retrospective study was designed to investigate the independent risks and specific biomarker for breast cancer-related ischemic stroke (BCRS). METHODS: Clinical features and laboratory findings were compared between BCRS group and breast cancer group without stroke, and further multivariate analyses were performed to predict independent risks factors for BCRS patients. A receiver operator characteristic (ROC) curve analysis was configured to estimate the diagnostic efficacy of each independent risk and the product of these risks and to obtain the optimal cut-off value of diagnosis, which was termed the BCRS Index. RESULTS: BCRS patients had elevated plasma D-dimer and CA153 levels and platelet-to-lymphocyte ratio (PLR), as well as more patients received endocrine therapy (all p ＜ 0.05). Moreover, multivariate analysis revealed that D-dimer levels (odds ratio [OR]: 1.002; 95% confidence interval [CI]: 1.001-1.003; p = 0.000), CA153 levels (OR: 1.005; 95% CI: 1.001-1.008; p = 0.007), PLR (OR: 1.010; 95% CI: 1.004-1.015; p = 0.001), and endocrine therapy (OR: 1.268; 95% CI: 1.087-1.479; p = 0.003) were identified as independent risks of BCRS. Furthermore, ROC analysis displayed that the product of risks had the best diagnostic efficacy, of which the area under the curve was 0.846 ± 0.28. The optimum cut-off point was 2.37 × 106/mL, which was termed the BCRS Index with higher diagnostic accuracy and validity. CONCLUSIONS: Endocrine therapy, as well as elevated plasma D-dimer and CA153 levels and PLR values may be independent risks for BCRS. Furthermore, BCRS Index should be served as a novel specific biomarker for BCRS, which is useful to distinguish BCRS for clinicians.

[Effect of screw blade position on proximal femoral nail anti-rotation internal fixation for unstable intertrochanteric fractures in the elderly].

OBJECTIVE: To investigate the effect of the screw blade position on the effectiveness of proximal femoral nail anti-rotation (PFNA) internal fixation for unstable intertrochanteric fractures in the elderly. METHODS: A clinical data of 131 elderly patients with unstable intertrochanteric fractures who were treated with PFNA internal fixation between January 2010 and January 2017 was retrospectively analyzed. According to the anteroposterior X-ray films, the screw blades were placed in the middle of the femoral neck in 72 patients (group A) and at one-third of the femoral neck in 59 patients (group B). There was no significant difference between the two groups ( P>0.05) in the gender, age, bone density, classification of fractures, other medical diseases, and the time between injury and operation. Multiple treatment indexes were analyzed, including complications, hip Harris score, the healing status of fracture, tip-apex distance (TAD), and the height of the tail nail. RESULTS: All patients were followed up 11-14 months, with an average of 12.1 months. All incisions healed by first intention with no complications. All fractures healed and no significant difference in bone healing time between the two groups ( Z=-0.190, P=0.849). At 6 months after operation, TAD was (2.23±0.07) cm in group A and (2.85±0.12) cm in group B, showing significant difference ( t=-47.643, P=0.000); and the height of the tail nail was (1.72±0.14) cm in group A and (0.53±0.26) cm in group B, showing significant difference ( t=31.031, P=0.000). According to the Harris score, the hip functions were rated as excellent in 48 cases, good in 15 cases, and poor in 9 cases in group A, while as excellent in 38 cases, good in 16 cases, and poor in 5 cases in group B, with no significant difference between the two groups ( Z=-0.075, P=0.941). CONCLUSION: For the unstable intertrochanteric fracture in the elderly, the PFNA internal fixation with appropriated TAD and the screw blades placed in the middle or at one-third of the femoral neck can obtain good effectiveness.

Adjacent two-level anterior cervical discectomy and fusion versus one-level corpectomy and fusion in cervical spondylotic myelopathy: Analysis of perioperative parameters and sagittal balance.

OBJECTIVES: The optimal surgical strategy for cervical spondylotic myelopathy (CSM) remains controversial; thus, the current study was designed to compare the outcomes of two different anterior approach surgeries for two-level CSM, namely, adjacent two-level anterior cervical discectomy and fusion (ACDF) and one-level anterior cervical corpectomy and fusion (ACCF). PATIENTS AND METHODS: A total of 53 patients who underwent adjacent two-level ACDF and 68 patients who underwent one-level ACCF in the Spinal Surgery Department from January 2010 to October 2017 were retrospectively analyzed. Independent sample t tests and chi-square tests were used to compare perioperative parameters (hospital stays, bleeding amounts and operation times), clinical parameters (Neck Disability Index scores and Visual Analog Scale scores for neck and arm pain), and radiologic parameters (difference in segmental height, T1 slope, C2-7 sagittal vertical axis, C2-7 lordosis, segmental angle, and fusion rate). RESULTS: The length of hospital stay (p < 0.01), bleeding amount (p < 0.01), operation time (p < 0.001) and difference in segmental height (p < 0.001) were significantly greater in the ACCF group than in the ACDF group, whereas C2-7 lordosis (p < 0.05) and the segmental angle (p < 0.001) were significantly lower in the ACCF group than in the ACDF group. Other parameters were not significantly different between the two groups. CONCLUSION: Both ACDF and ACCF provided satisfactory clinical outcomes and fusion rates for CSM. However, adjacent two-level ACDF was associated with shorter hospital stays, less blood loss, shorter operative times, fewer differences in segmental height and greater improvement in segmental lordotic curvature. On most occasions, when either surgical method could be selected, adjacent two-level ACDF as a surgical treatment for CSM may be a worthwhile alternative method to one-level ACCF.

The modified anterior ellipsoidal cap titanium cable tension band for comminuted patellar fractures.

PURPOSE: The purpose of this study was to assess the outcomes in a series of patients, who underwent cerclage and figure-of-eight tension band wiring using a single titanium cable for comminuted patellar fractures. METHODS: We describe a modified tension band technique using a single titanium cable to create an ellipsoidal cap structure that combines the circumferential and figure-of-eight wrapping in the fixation of closed Association for the Study of Internal Fixation/Orthopaedic Trauma Association 34C2 and 34C3 patellar fractures. We retrospectively reviewed 25 patients (16 males and 9 females, mean age 54 years) who underwent the described fixation technique between 2015 and 2017. Postoperative function was evaluated using the Böstman score. RESULTS: At the mean follow-up of 25 months (range 17-39 months), the mean Böstman score was 27.3 ± 2.6 points (range 23-30). Eighteen patients (72%) had excellent results (score ≥28); seven patients (28%) had good results (score 20-27); and no patients had an unsatisfactory result (score < 20). All surgical incisions healed without major wound complications. Two patients reported minor complications (soft tissue irritation, cellulitis). No patients demonstrated loss of reduction or implant failure during the follow-up period. CONCLUSION: The modified anterior ellipsoidal cap tension band using a single titanium cable created an effective tension band structure in the treatment of comminuted patella fractures. It is a simple operative technique that produced a stable fixation construct, which allowed early functional rehabilitation and weight-bearing with a high rate of excellent outcomes at 2 years after surgery.

[Effectiveness analysis of distal radius microplate locking plate for treatment of displaced fracture of medial clavicle].

OBJECTIVE: To investigate and evaluate the effectiveness of the distal radius microplate locking plate for the treatment of displaced fracture of medial clavicle. METHODS: Between January 2013 and June 2017, 18 cases of obvious displaced fracture of medial clavicle were treated with distal radius microlocking plate. There were 10 males and 8 females, with an average age of 51.4 years (range, 18-88 years). Causes of injury included traffic accident injury in 15 cases, heavy object injury in 3 cases; all of them were closed injury. According to Edinburgh classification, 15 cases were ⅠB1 type and 3 cases were ⅠB2 type. Fracture displacement was 12-21 mm (mean, 16.3 mm). The time from injury to operation was 3-7 days (mean, 4.3 days). After operation, the clinical healing and complications of fracture were observed, and shoulder function was evaluated according to Rockwood's scoring criteria. RESULTS: No incisional infection, neurovascular injury, or other early complications occurred. All 18 patients were followed up 8-15 months (mean, 12 months). All fractures reached clinical osseous union, and the healing time was 8-24 weeks (mean, 16.6 weeks). Postoperative plate loosening occurred in 1 case, which was removed surgically, while other patients did not suffer from complications such as bone nonunion, displacement, internal fixator loosening, and loss of reduction. At last follow-up, according to Rockwood's scoring criteria, the results were excellent in 12 cases and good in 6 cases. CONCLUSION: The distal radius microplate locking plate is effective for the treatment of displaced medial clavicle fracture, which has few complications, and is feasible for early functional exercise, and is helpful for the recovery of shoulder joint function.

Identification of Serum Biomarkers for Ischemic Penumbra by iTRAQ-Based Quantitative Proteomics Analysis.

PURPOSE: Ischemic penumbra is the main therapeutic target for acute ischemic stroke. The aim in this study is to investigate the potential serum biomarkers of penumbra that could fulfill a complementary role in the acute stroke clinical decision-making process. EXPERIMENTAL DESIGN: An established focal cerebral ischemia model is applied in rats. Using isobaric tags for relative and absolute quantitation combined with liquid chromatography-tandem mass spectrometry, the global expression profiles of proteins in ischemic penumbra tissue and serum from rats subjected to different ischemic times are identified and quantified. Candidate biomarkers are screened out with bioinformatics analysis and further validated by western blotting. RESULTS: Herein, a total of 4568 proteins in the penumbra and 1915 proteins in the serum are identified. Two proteins related to the penumbra, RHOA, and CDC42, are screened out through an integrative analysis. The expression levels of RHOA and CDC42 in the penumbra and serum gradually increase synchronously with the prolonged ischemia time. CONCLUSIONS AND CLINICAL RELEVANCE: The study provides the results of a proteomic analysis to identify serum biomarkers of the penumbra. Upregulation of RHOA and CDC42 may be useful for the early assessment of ischemic penumbra and could serve as potential serum biomarkers.

Leptin attenuates cerebral ischemic injury in rats by modulating the mitochondrial electron transport chain via the mitochondrial STAT3 pathway.

BACKGROUND: According to recent studies, leptin may exert a neuroprotective function by affecting the phosphorylation of signal transducer and activator of transcription 3 (STAT3). During stress, STAT3 regulates mitochondrial oxidative stress and reduces apoptosis. OBJECTIVE: In the present study, we hypothesized that leptin increases STAT3 phosphorylation in the mitochondria and protects against mitochondrial oxidative stress in rats subjected to permanent middle cerebral artery occlusion (MCAO). RESULTS: Leptin reduced reactive oxygen species (ROS) production, and we confirmed that the mechanism underlying this change involved the enzymatic activities of mitochondrial respiratory chain complexes I and II. In addition, leptin increased the level of STAT3 Ser727 phosphorylation in the mitochondria. CONCLUSIONS: Based on these results, leptin may regulate mitochondrial respiratory chain enzymatic activities via mitochondria-targeted STAT3 to reduce ROS production and protect brain tissues from mitochondrial oxidative stress during cerebral ischemia.

Decreased miR-146a expression in acute ischemic stroke directly targets the Fbxl10 mRNA and is involved in modulating apoptosis.

BACKGROUND: miR-146a, a strong pro-apoptotic factor in some pathophysiological processes, is reported to be involved in ischemic stroke (IS), though its role remains unclear. Fbxl10 is an active anti-apoptotic factor and a predicted target of miR-146a. We hypothesized that dysregulation of miR-146a contributes to ischemic injury by targeting Fbxl10. METHODS: Circulating miRNAs were detected by miRNA microarray and qRT-PCR. miR-146a targets were predicted using bioinformatics and confirmed with a dual luciferase reporter assay. We used an in vitro ischemic model of oxygen-glucose deprivation and reperfusion (OGD/R) to mimic cerebral ischemia/reperfusion (I/R) conditions. Expression of miR-146a, Fbxl10 and Bcl2l2 mRNAs, and Fbxl10 and Bcl2l2 proteins was verified by qRT-PCR and Western blotting. The effects of miR-146a on neuronal cell apoptosis were evaluated by flow cytometry. RESULTS: A significant reduction in miR-146a expression was observed in acute ischemic stroke (AIS). A dual-luciferase reporter assay showed that Fbxl10, but not Bcl2l2, is a target of miR-146a. Transfection with miR-146a mimics promoted apoptosis in SK-N-SH cells and significantly reduced expression of Fbxl10. Conversely, miR-146a inhibition attenuated OGD/R-induced neuronal cell death and significantly up-regulated Fbxl10 expression. CONCLUSIONS: miR-146a expression was significantly down-regulated in AIS, and Fbxl10 was identified as a target of miR-146a. Moreover, up-regulation of Fbxl10, a miR-146a target, likely protects neurons from ischemic death.

[Effectiveness of cerclage and a figure-of-eight tension band by a single titanium wire in treatment of patellar fracture].

Objective: To estimate the outcome of cerclage followed by a figure-of-eight tension band with a single titanium wire for the treatment of patellar fracture. Methods: A retrospective analysis was made on the clinical data of 46 patients with patellar fractures treated between June 2012 and November 2014. There were 30 males and 16 females, aged 20-86 years (mean, 54 years). The fracture causes included falling in 27 cases, traffic accident in 16 cases, and knock in 3 cases. There were 41 cases of closed fractures and 5 cases of open fracture. The injury located at the left side in 24 cases and the right side in 22 cases. According to AO classification, fracture was rated as type 34-A in 3 cases, as type 34-B in 1 case, as type 34-C1 in 7 cases, as type 34-C2 in 13 cases, and as type 34-C3 in 22 cases. The time between injury and operation ranged 1-12 days (mean, 3.7 days). During operations, a single titanium wire was used to pass around the patellar, followed a figure-of-eight wrapping, to tight and fix at the tension of 35 kg. Results: All incisions healed primarily. The patients were followed up 20.6 months on average (range, 6-24 months). Partial wire loosening was found in 2 cases, irritation of skin or soft tissue in 1 case. The X-ray examination showed bony healing at 3 months after operation, without breakage of titanium wire. The internal fixation was removed in 38 cases at 12 months after operation. According to the Böstman rating score, the mean score was 28.34 (range, 24-30) at 12 months after ope-ration; the results were excellent in 42 cases and good in 4 cases, with an excellent and good rate of 100%. Conclusion: For patellar fracture, cerclage followed by a figure-of-eight tension band with a single titanium wire is able to achieve an effective stability and to allow early motion for patient with less complication.

MicroRNA-146a down-regulation correlates with neuroprotection and targets pro-apoptotic genes in cerebral ischemic injury in vitro.

MicroRNAs (miRNAs) are short, non-coding RNAs that negatively regulate target gene expression, and play an important role in cerebral ischemic injury. MiR-146a has been reported to be highly related to cell invasion, metastasis, immunity, inflammation and apoptosis. Previous studies have indicated that miR-146a can either inhibit or promote apoptosis through different pathophysiological processes. In our previous study, miR-146a in the blood was down-regulated during acute ischemic stroke. However, the connection between miR-146a and acute cerebral ischemic injury and the mechanism underlying the connection remain unclear. Here, we aimed to investigate the role of miR-146a and its possible target genes in human SK-N-SH cells subjected to 16h of oxygen-glucose deprivation and 12h of reperfusion (OGD/R) injury. Cells were transfected with miR-146a mimic or inhibitor to alter the expression of miR-146a. MiR-146a in the SK-N-SH cells was down-regulated after OGD/R injury. Moreover, bioinformatics analysis and dual luciferase assays demonstrated that miR-146a directly recognized the 3'-UTR of the pro-apoptotic genes, Caspase7 and Bcl-2-associated transcription factor 1 (Bclaf1). Furthermore, miR-146a over-expression effectively decreased the mRNA and protein expression of Caspase7 and Bclaf1, and aggravated OGD/R-induced cell apoptosis; in contrast, miR-146a down-regulation was neuroprotective. In conclusion, our study revealed that miR-146a contributes to OGD/R injury in vitro, while negatively regulating the pro-apoptotic genes, Caspase7 and Bclaf1. This special mechanism provides new insight into miRNA regulatory networks. In addition, miR-146a may offer a potential therapeutic approach to cerebral ischemic injury.