Monocyte-Derived Macrophages Aggravate Cardiac Dysfunction After Ischemic Stroke in Mice.

BACKGROUND: Cardiac damage induced by ischemic stroke, such as arrhythmia, cardiac dysfunction, and even cardiac arrest, is referred to as cerebral-cardiac syndrome (CCS). Cardiac macrophages are reported to be closely associated with stroke-induced cardiac damage. However, the role of macrophage subsets in CCS is still unclear due to their heterogeneity. Sympathetic nerves play a significant role in regulating macrophages in cardiovascular disease. However, the role of macrophage subsets and sympathetic nerves in CCS is still unclear. METHODS AND RESULTS: In this study, a middle cerebral artery occlusion mouse model was used to simulate ischemic stroke. ECG and echocardiography were used to assess cardiac function. We used Cx3cr1GFPCcr2RFP mice and NLRP3-deficient mice in combination with Smart-seq2 RNA sequencing to confirm the role of macrophage subsets in CCS. We demonstrated that ischemic stroke-induced cardiac damage is characterized by severe cardiac dysfunction and robust infiltration of monocyte-derived macrophages into the heart. Subsequently, we identified that cardiac monocyte-derived macrophages displayed a proinflammatory profile. We also observed that cardiac dysfunction was rescued in ischemic stroke mice by blocking macrophage infiltration using a CCR2 antagonist and NLRP3-deficient mice. In addition, a cardiac sympathetic nerve retrograde tracer and a sympathectomy method were used to explore the relationship between sympathetic nerves and cardiac macrophages. We found that cardiac sympathetic nerves are significantly activated after ischemic stroke, which contributes to the infiltration of monocyte-derived macrophages and subsequent cardiac dysfunction. CONCLUSIONS: Our findings suggest a potential pathogenesis of CCS involving the cardiac sympathetic nerve-monocyte-derived macrophage axis.

Evolutionary origin and establishment of a dioecious diploid-tetraploid complex.

Polyploids recurrently emerge in angiosperms, but most polyploids are likely to go extinct before establishment due to minority cytotype exclusion, which may be specifically a constraint for dioecious plants. Here we test the hypothesis that a stable sex-determination system and spatial/ecological isolation facilitate the establishment of dioecious polyploids. We determined the ploidy levels of 351 individuals from 28 populations of the dioecious species Salix polyclona, and resequenced 190 individuals of S. polyclona and related taxa for genomic diversity analyses. The ploidy survey revealed a frequency 52% of tetraploids in S. polyclona, and genomic k-mer spectra analyses suggested an autopolyploid origin for them. Comparisons of diploid male and female genomes identified a female heterogametic sex-determining factor on chromosome 15, which probably also acts in the dioecious tetraploids. Phylogenetic analyses revealed two diploid clades and a separate clade/grade of tetraploids with a distinct geographic distribution confined to western and central China, where complex mountain systems create higher levels of environmental heterogeneity. Fossil-calibrated phylogenies showed that the polyploids emerged during 7.6-2.3 million years ago, and population demographic histories largely matched the geological and climatic history of the region. Our results suggest that inheritance of the sex-determining system from the diploid progenitor as intrinsic factor and spatial isolation as extrinsic factor may have facilitated the preservation and establishment of polyploid dioecious populations.

Total femur replacement with 18 years of follow-up: A case report.

BACKGROUND: Osteosarcoma is one of the most common primary malignant bone tumors and is more common in adolescents. The femur is the most common site of osteosarcoma, and many patients require total femur replacement. We reviewed the relevant literature and case findings, summarized and analyzed this case in combination with relevant literature, and in doing so improved the understanding of the technology. CASE SUMMARY: The case we report was a 15-year-old patient who was admitted to the hospital 15 days after the discovery of a right thigh mass. The diagnosis was osteosarcoma of the right femoral shaft. After completion of neoadjuvant chemotherapy and preoperative preparation, total right femoral resection + artificial total femoral replacement was performed. Then, chemotherapy was continued after surgery. The patient recovered well after treatment, and the function of the affected limb was good. No recurrence, metastasis, prosthesis loosening, dislocation, fracture or other complications were found during 18 years of follow-up. At present, the patient can still work and lives normally. The results of the medium- and long-term follow-up were satisfactory. CONCLUSION: Artificial total femur replacement is a feasible limb salvage operation for patients with femoral malignant tumors, and the results of medium- and long-term follow-up are satisfactory.

Isoflurane Attenuates Cerebral Ischaemia-Reperfusion Injury via the TLR4-NLRP3 Signalling Pathway in Diabetic Mice.

Ischaemic stroke is a severe disease worldwide. Restoration of blood flow after ischaemic stroke leads to cerebral ischaemia-reperfusion injury (CIRI). Various operations, such as cardiac surgery with deep hypothermic circulatory arrest, predictably cause cerebral ischaemia. Diabetes is related to the occurrence of perioperative stroke and exacerbates neurological impairment after stroke. Therefore, the choice of anaesthetic drugs has certain clinical significance for patients with diabetes. Isoflurane (ISO) exerts neuroprotective and anti-neuroinflammatory effects in patients without diabetes. However, the role of ISO in cerebral ischaemia in the context of diabetes is still unknown. Toll-like receptor 4 (TLR4) and NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation play important roles in microglia-mediated neuroinflammatory injury. In this study, we treated a diabetic middle cerebral artery occlusion mouse model with ISO. We found that diabetes exacerbated cerebral ischaemia damage and that ISO exerted neuroprotective effects in diabetic mice. Then, we found that ISO decreased TLR4-NLRP3 inflammasome activation in microglia and the excessive autophagy induced by CIRI in diabetic mice. The TLR4-specific agonist CRX-527 reversed the neuroprotective effects of ISO. In summary, our study indicated that ISO exerts neuroprotective effects against the neuroinflammation and autophagy observed during diabetic stroke via the TLR4-NLRP3 signalling pathway.

[Current advances in research of semaphorin 3A:a potential target for the treatment of nospecific low back pain].

Nonspecific low back pain is closely associated with afferent nerve ingrowth into degenerated IVDs and increasing the inflammatory response. Members of the class 3 semaphorins signal their response through two prominent receptors; the NRP (Neuropilin-1) and the Plexin A. Sema3A (Semaphorin3A) is primarily known for their role in modulating neuronal survival as well as neurite outgrowth and guidance via regulation of Sema3A-NRP-1-plexinA signal pathway. Also, sema3A is shown to be conductive to innervate the inner painful degenerated IVDs (Intervertebral discs). Furthermore, sema3A is thought to act as a barrier to endothelial cells survival and migration on vascular endothelial growth factor (VEGF) and inhibition of KLF5-induced (Krüppel-like factor 5) inflammatory mediators within degenerated IVDs. Therefore, Sema3A produce a new perspective of dual-action therapeutic agent for attenuating the regulator of innervation and angiogenesis into degenerated IVDs and inhibition of KLF5-induced inflammation.

Macrophage-NLRP3 Inflammasome Activation Exacerbates Cardiac Dysfunction after Ischemic Stroke in a Mouse Model of Diabetes.

Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.

Association between Nonalcoholic Fatty Liver Disease and Carotid Artery Disease in a Community-Based Chinese Population: A Cross-Sectional Study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases with a high prevalence in the general population. The association between NAFLD and cardiovascular disease has been well addressed in previous studies. However, whether NAFLD is associated with carotid artery disease in a community-based Chinese population remained unclear. The aim of this study was to investigate the association between NAFLD and carotid artery disease. METHODS: A total of 2612 participants (1091 men and 1521 women) aged 40 years and older from Jidong of Tangshan city (China) were selected for this study. NAFLD was diagnosed by abdominal ultrasonography. The presence of carotid stenosis or plaque was evaluated by carotid artery ultrasonography. Logistic regression was used to analyze the association between NAFLD and carotid artery disease. RESULTS: Participants with NAFLD have a higher prevalence of carotid stenosis (12.9% vs. 4.6%) and carotid plaque (21.9% vs. 15.0%) than those without NAFLD. After adjusting for age, gender, smoking status, income, physical activity, diabetes, hypertension, triglyceride, waist-hip ratio, and high-density lipoprotein, NAFLD is significantly associated with carotid stenosis (odds ratio [OR]: 2.06, 95% confidence interval [CI]: 1.45-2.91), but the association between NAFLD and carotid plaque is not statistically significant (OR: 1.10, 95% CI: 0.8-1.40). CONCLUSION: A significant association between NAFLD and carotid stenosis is found in a Chinese population.

[Application of Jintian'ge capsule in treatment of vertebral compression fracture in senile osteoporosis patients].

To study the clinical application of Jintian'ge capsule in treatment of vertebral compression fracture in senile osteoporosis patients. In the study, 69 senile osteoporotic vertebral compression fracture patients hospitalized in our hospital between January 2012 and June 2014 were selected and randomly divided into the control group and the treatment group. Patients in the control group were treated by percutaneous kyphoplasty (PKP), while those in the treatment group were given Jintian'ge capsule in addition to PKP. Efforts were made to visit the patients before the surgery and in three month after that, observe and compared the vertebral height, Cobb's angle, bone density, visual analogue scale (VAS) and Oswestry disability index between patients in the two groups. According to the findings, compared with before the treatment, patients in the two groups showed significant improvements in the vertebral height, Cobb's angle, bone density, VAS and Oswestry disability index three months after the surgery (P < 0.05); During the visit three months after the treatment, compared with the control group, the treatment group showed notable increases in all parameters (P < 0.05), particularly in the vertebral height, VAS and Oswestry disability index (P < 0.05). Based on the above findings, Jintian'ge capsule is applicable in adjuvant therapy after the osteoporotic vertebral compression facture PKP surgery.

[Antiproliferative effects of LY294002 on MCL Jeko-1 cell line and its mechanism].

This study was aimed to investigate the effects of LY294002, a specific inhibitor of phosphatidylinositol 3-kinase, on growth and apoptosis of MCL Jeko-1 cell line and its mechanism. The proliferation inhibitory rate of Jeko-1 cells treated by different doses of LY294002 was assayed by MTT method; the level of apoptosis of Jeko-1 cells was detected by flow cytometry; the expression level of apoptosis-related protein Cyclin D1, Bcl-2, procaspase-3 and PI3K/Akt signaling pathway protein phosphorylated-Akt (p-Akt), phosphorylated-TOR (p-mTOR), phosphorylated-P70S6K (p-P70S6K) phosphorylated-Akt (p-Akt) in Jeko-1 cells were determined by Western blot. The results showed that the growth of Jeko-1 cell line was inhibited by LY294002. The apoptosis rates of Jeko-1 cells treated with 0, 5, 10 and 20 µmol/L of LY294002 for 24 hours were (3.25 ± 1.27)%, (11.34 ± 2.35)%, (22.81 ± 2.74)%, (43.61 ± 3.48)% respectively, the difference between them was statistically significant (P < 0.01). Phosphorylation levels of PI3K/Akt signaling pathway protein p-Akt, p-mTOR, p-P70S6K decreased, the expression of apoptosis-related protein cyclin D1, Bcl-2, procaspase-3 was down-regulated.It is concluded that the LY294002 can inhibit Jeko-1 cell proliferation, which may be realized through down-regulating the phosphorylation level of p-Akt, p-mTOR, p-P70S6K, inhibiting the P13k/Akt signaling pathway, and promoting the cell apoptosis.

[Preliminary investigation of animal model of tibial defection fracture made by drilling hole method ].

OBJECTIVE: To compare the differences in damage degree, healing time and healing process between two animal models of defection fracture and provide the research data for the establishment of a new animal model. METHODS: Sixty male SPF Spragur-Dawley rats were divided randomly into control group, sawing group and drilling hole group, with 20 rats in each group. Animals of drilling hole group were treated with hone drill and made an 1 mm hole on tibial plateau animals of sawing group were treated with saw and made an 3 mm defection on tibial plateau; nothing to do in animals of control group. The rats were respectively killed at 2nd, 4th weeks after operation, bone density, bone ash quantity, contents of bone Ca, P were detected. RESULTS: At the 2nd week after operation, bone density, bone ash quantity, contents of bone Ca, P in drilling hole group and sawing group were significantly lower than that of the control group (P < 0.05 or P < 0.01). Two animal models of drilling hole group and sawing group were similar in X-ray films and pathology investigations. At the 4th week after operation, there were no significant defference in bone density and bone ash quantity among three groups (P > 0.05). Rats of sawing group showed more poroma and inflammatory infiltration in histological examination. CONCLUSION: Drilling hole method and sawing method could be used to make animal model of defection fracture, two methods showed similar damage degree, healing time and healing process, hut drilling hole method have advantages of simple operation, easily control damage degree and less inflammatory infiltration and bone disunion.

[Case-control studies between two methods of minimally invasive surgery and traditional open operation for thoracolumbar fractures].

OBJECTIVE: To investigate the surgical therapeutic result of thoracolumbar fracture treated by two minimally invasive surgery or by traditional open operation. METHODS: From June 2004 to April 2010, 76 patients (45 males and 31 females, with an average age of 36.4 years, ranging from 21 to 58 years) with thoracolumbar fracture were divided into three groups. In group A, 24 patients were treated with minimally invasive internal fixation by endoscope. In group B, 20 patients were treated by Sextant percutaneous pedicle screws fiaxation. In group C, 32 patients were performed with traditional open fixation surgery. The perioperative index and radiographic factor were compared among the three groups. RESULTS: All patients were followed-up for 1 year in average. The internal fixation devices were taken out averaged 1 year after operation,there were no complications related to the internal fixaton systems. The perioperative index of groups A and B including the incision size, surgical blood loss, surgical draining loss, hospital stay time and post-operation VAS score were significant smaller than group C (P < 0.05). The Cobb's angle, sagittal index, and anterior height of the fracture vertebral body were all significantly different between pre-operation and post-operation in each group (P < 0.05). CONCLUSION: These two methods of minimally invasive surgical treatments are effective and safe for patients with thoracolumbar fracture,because of less damage to muscles, less blood loss and quicker recovery, compared to the traditional open operation.

[Minimally invasive trochanteric antegrade nail fixation for the treatment of intertrochanteric fractures of femur in elder].

OBJECTIVE: To evaluate the clinical effect of minimally invasive Trochanteric Antegrade Nail (TAN) for the treatment of intertrochanteric fractures of femur in elder. METHODS: From January 2005 to June 2008, 80 patients with intertrochanteric fractures of femur were treated with minimally invasive fixation of Trochanteric Antegrade Nail. There were 16 males and 64 females with an average age of 75 years ranging from 65 to 93 years. According to Evans classification, there were 8 cases of type I, 32 of type II, 30 of type III, 6 of type IV and 4 of type V. After the operation of minimally invasive Trochanteric Antegrade Nail fixation,patients begun to do the continuous passive motion (CPM) and active motion of the injured hip joint and knee joint. RESULTS: All patients were followed from 5 to 18 months with an average of 10 months. All factures were healing in time from 10 to 14 weeks with none screw breakage. Proximal screw exiting out about 0.5 cm occurred in 3 patients without obvert symptom. Three patients appeared lower limb deep venous thrombosis and were cured with medicine. According to the scales of Sanders, pain score was 9.08 +/- 1.19, ambulation score 8.85l +/- 1.09, function score 9.10 +/- 1.27, muscle strength score 9.13 +/- 1.18, daily life score 8.91 +/- l.07, X-ray evaluation score 9.34 +/- 1.09, so as the results were excellent in 56 cases, good in 20, poor in 4. CONCLUSION: With the advantage of mini-invasion, operative convenience and stable fixation, minimally invasive TAN fixation is an effective method for intertrochanteric fractures in elder.

Endoscopic third ventriculostomy in the management of communicating hydrocephalus: a preliminary study.

OBJECT: The purpose of this study was to elucidate the efficacy of endoscopic third ventriculostomy (ETV), the procedure's indications, and prognosis after treatment in patients with communicating hydrocephalus. METHODS: Between August 2002 and January 2007, 32 ETVs were performed in 32 patients with communicating hydrocephalus (24 men and 8 women) at the authors' institution. The patients ranged in age from 25 to 82 years old (mean 61.4 years), and had a follow-up of 2-53 months (mean 14 months). The patients were divided into 2 groups according to the results of preoperative tests. The first group included 17 patients with idiopathic normal-pressure hydrocephalus, and the second group included 15 patients with secondary communicating hydrocephalus who experienced meningitis, spontaneous subarachnoid hemorrhage, or hypertensive intracranial hemorrhage. Both univariate and multivariate statistical analyses were performed to assess the prognostic relevance of the cause of communicating hydrocephalus, the preoperative Kiefer scale score, and hydrodynamic findings in predicting the results after ETV. RESULTS: Excellent results were achieved in 25% of patients, good results in 40.6%, satisfactory in 12.5%, and poor in 21.9% of patients. The authors found that the preoperative Kiefer score and the patient's age had a high correlation with overall ETV outcome. Nineteen patients (59.3%) with comparatively mild symptoms (Kiefer Score 0-10) had a favorable course after ETV. Three patients in this group showed a satisfactory course, and 1 had a poor course. Among patients with Kiefer scores of 11-21 points, 6 (46%) had a favorable course, 1 (8%) a satisfactory one, and 6 (46%) had no relief from symptoms at all. Fourteen (88%) of 16 patients < 65 years of age had a favorable course after ETV. However, only 7 of 16 patients (44%) > 65 years showed definite improvement after ETV. Among the Kiefer score indicators, the preoperative mental state played an important role in predicting ETV outcome. The results of this test imply that the relative risk of ETV failure in a patient with a concentration disorder is about 2 times that in a patient without. Of the 7 patients with secondary communicating hydrocephalus who had elevated intracranial pressure (range 205-265 mm H2O), 5 patients had a favorable result from ETV. Meanwhile, in the same group, 5 (63%) of 8 patients with normal intracranial pressure had an excellent or good result. In comparing the findings on cine MR imaging before and after surgery, there was evidence of a decrease in the velocity and quantity of cerebrospinal fluid flow in the aqueduct after ETV. CONCLUSIONS: The new hydrodynamic concept of hydrocephalus opens the possibility that ETV may be an effective treatment for communicating hydrocephalus. It thus constitutes an interchangeable alternative to shunting. Patient age, analysis of the causes of hydrocephalus, and mental state evaluation play important roles in outcome prediction in patients with communicating hydrocephalus who undergo ETV. Randomized clinical studies are needed to explore further the role of this treatment in communicating hydrocephalus therapy.