Increased Cyclic Adenosine Monophosphate Responsive Element is Closely Associated with the Pathogenesis of Drug-resistant Epilepsy.

BACKGROUND: Drug-resistant epilepsy (DRE) is a refractory neurological disorder. There is ample evidence that suggest that γ-aminobutyric acid-a (GABAA) receptors could be one of the mechanisms responsible for the development of drug resistance in epilepsy. It is also known that the cAMP response element binding protein (CREB) plays a possible key role in the transcriptional regulation of GABAA. OBJECTIVE: This study explores the role of CREB in the development of DRE and the effect of CREB on GABA-related receptors in DRE. METHODS: The CREB expression was increased or decreased in the hippocampus of normal rats by lentiviral transfection, who then underwent the lithium-pilocarpine-induced epilepsy model. Phenobarbital (PB) sodium and carbamazepine (CBZ) were used to select a drug-resistant epileptic model. The expression levels of GABAA receptor α1, ß2, and γ2 subunits and CREB protein were measured in the rat hippocampus by western blot and fluorescent quantitative PCR. RESULTS: The frequency and duration of seizures increased in the overexpression group compared to that in the control group. In addition, the severity, frequency, and duration of seizures decreased in the group with decreased expression. The hippocampus analysis of the expression levels of the CREB protein and CREB mRNA yielded similar findings. Altering the CREB protein expression in the rat hippocampus could negatively regulate the expression and transcript levels of GABAA receptors α1, ß2, and γ2, suggesting that CREB may serve as a potential target for the development of treatment protocols and drugs for epilepsy. CONCLUSION: Our study shows that enhanced CREB expression promotes the development of DRE and negatively regulates GABAA receptor levels and that the inhibition of CREB expression may reduce the incidence of DRE.

Case report: Inspiration from a rare fatal heart perforation after percutaneous vertebroplasty.

The principal benefit of employing percutaneous vertebroplasty (PVP) for managing osteoporotic vertebral compression fractures lies in its capacity to facilitate early mobilization in elderly patients, thereby effectively avoiding the potential catastrophic complications associated with prolonged bedridden states. However, bone cement leakage, as the most common complication of PVP, may have fatal consequences. Here, we report a case involving an 85-year-old male patient with L1 vertebral compression fracture who underwent PVP at our hospital and was discharged on the same day of the surgical intervention. Subsequently, the patient experienced symptoms of chest tightness and palpitations. Cardiac ultrasound examination revealed pericardial effusion, while pulmonary computed tomographic angiography (CTA) demonstrated a strip high-density shadow in the right ventricular area. Finally, it was determined that the perforation of the right ventricular wall was caused by bone cement embolism. Through this comprehensive case report, we aim to deepen the understanding of orthopedic doctors on the importance of preventing bone cement leakage.

Impact of inclusive leadership on employees' innovative behavior: A relational silence approach.

Introduction: Although employees' silence is a common phenomenon in organizations, the mediating role of relational silence has not been studied in inclusive leadership and innovative behavior. In this study, based on the theory of social exchange, relational silence is used as a mediating variable to explore the internal mechanisms of inclusive leadership on employees' innovative behavior. Methods: Data from 263 in-service leaders and employees were collected using convenience sampling and analyzed using Amos and SPSS statistical software package via questionnaires distributed to companies in six cities in the Guangdong province of China. Results: The results showed that inclusive leadership has a significant positive predictive effect on employees' innovative behavior (ß = 0.590, p < 0.01), while inclusive leadership is negative and significantly correlated with relational silence (ß = -0.469, p < 0.01). More so, relational silence has a significant negative correlation with employees' innovative behavior (ß = -0.408, p < 0.01), and relational silence partially mediates the relationship between inclusive leadership and employee innovation behavior. Discussion: The mediating role of relational silence between inclusive leadership and employees' innovative behavior is revealed for the first time, theoretically broadening and enriching the connotation of inclusive leadership's influence mechanism on employees' innovative behavior and providing new ideas in practice for constructing inclusive leadership styles, reducing the incidence of relational silence, and evoking employees' innovative behavior.

Diffuse pigmented villonodular synovitis treated with arthroscopic total synovial peel.

BACKGROUND: Diffuse pigmented villonodular synovitis (PVNS) is prone to recurrence after surgery, and it is difficult to achieve a long-term complete cure. OBJECTIVE: To reduce the recurrence rate of PVNS, the author pioneered the arthroscopic total synovial peel (ATSP). METHODS: From March 2014 to July 2020, a total of 19 patients (6 males and 13 females) with diffuse PVNS of the knee were treated in our department and underwent ATSP. It's 'peel' rather than simple excision. This method is similar to peeling bark. Relapse rates and functional scores were determined, with follow-ups ranging from 12 to 72 months, on average 36 months. RESULTS: Treatment efficacy was assessed by imaging and functional scores. Imaging results indicated a recurrence rate of 10.5%. In patients without recurrence, the visual analog score (VAS) decreased from 4.76 ± 2.02 preoperatively to 1.56 ± 1.15 postoperatively. The Tegner-Lysholm knee function score (TLS) score increased from 67.76 ± 15.64 preoperatively to 90.32 ± 8.32 postoperatively. Compared with the literature, ATSP significantly reduces the postoperative recurrence rate of diffuse PVNS. The preliminarily findings suggest that this approach could greatly reduce the recurrence rate of postoperative PVNS in follow-up studies. CONCLUSION: This approach may be a viable option for treating diffuse PVNS via arthroscopy and is worthy of clinical consideration.

Evaluation of a Functional Single Nucleotide Polymorphism of the SARS-CoV-2 Receptor ACE2 That Is Potentially Involved in Long COVID.

Since the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, SARS-CoV-2 has led to a global coronavirus disease 2019 (COVID-19) pandemic. A better understanding of the SARS-CoV-2 receptor ACE2 at the genetic level would help combat COVID-19, particularly for long COVID. We performed a genetic analysis of ACE2 and searched for its common potential single nucleotide polymorphisms (SNPs) with minor allele frequency >0.05 in both European and Chinese populations that would contribute to ACE2 gene expression variation. We thought that the variation of the ACE2 expression would be an important biological feature that would strongly affect COVID-19 symptoms, such as "brain fog", which is highlighted by the fact that ACE2 acts as a major cellular receptor for SARS-CoV-2 attachment and is highly expressed in brain tissues. Based on the human GTEx gene expression database, we found rs2106809 exhibited a significant correlation with the ACE2 expression among multiple brain and artery tissues. This expression correlation was replicated in an independent European brain eQTL database, Braineac. rs2106809*G also displays significantly higher frequency in Asian populations than in Europeans and displays a protective effect (p = 0.047) against COVID-19 hospitalization when comparing hospitalized COVID-19 cases with non-hospitalized COVID-19 or SARS-CoV-2 test-negative samples with European ancestry from the UK Biobank. Furthermore, we experimentally demonstrated that rs2106809*G could upregulate the transcriptional activity of ACE2. Therefore, integrative analysis and functional experiment strongly support that ACE2 SNP rs2106809 is a functional brain eQTL and its potential involvement in long COVID, which warrants further investigation.

Artificial Dermal Scaffold Loaded with Platelet-Rich Plasma Promotes Wound Healing in Pigs by Favoring Angiogenesis.

BACKGROUND The development of artificial dermis provides a new therapeutic method for full-thickness skin defects. However, the slow regeneration of blood vessels in the wound site still cannot be solved perfectly. In our study, we combined platelet-rich plasma (PRP) with Lando® artificial dermal scaffold to promote vascular regeneration and wound healing in pigs. MATERIAL AND METHODS First, PRP was compounded with the artificial dermal scaffold. Then, this material was co-cultured with human vascular endothelial cells (HUVECs) and the growth and proliferation of HUVECs were assessed. Bama miniature pigs wound models were fabricated, the materials were transplanted into the skin defect, and wound healing and blood vessel regeneration were assessed by HE staining and CD31 immunohistochemistry. RESULTS Scanning electron microscopy (SEM) showed that PRP formed round particles on the surface of the artificial dermis material. Cell co-culture experiments showed that the PRP composite artificial dermal scaffold can promote the growth and proliferation of HUVECs. CCK8 experiments demonstrated that the number of cells in the PRP composites group on days 2, 3, 4, and 5 was higher than that in the material alone group (P<0.01). The results of animal experiments showed that PRP composite artificial dermal material can promote wound healing. Histological staining and immunohistochemical staining indicated that the PRP composites group promoted epithelial tissue thickening and blood vessel regeneration in wounds (P<0.001). CONCLUSIONS Our experimental results showed that the artificial dermal scaffold loaded with platelet-rich plasma can promote the revascularization of wounds and accelerated wound healing.

Higher Cerebral Small Vessel Disease Burden in Patients With Small Intracerebral Hemorrhage.

Objective: To investigate the association between cerebral small vessel disease (SVD) and hematoma volume in primary intracerebral hemorrhage (ICH). Methods: Patients from a prospective ICH cohort were enrolled. Admission and follow-up CT scan within 72 h after onset were reviewed to calculate the final hematoma volume. We evaluated cortical superficial siderosis and the global SVD score, including white matter hyperintensities, lacunes, enlarged perivascular space, and cerebral microbleeds on MRI. We conducted the multivariate logistic regression analyses to explore the association between SVD markers and small ICH, as well as hematoma volume. Hematoma location was stratified into lobar and non-lobar for subgroup analysis. Results: A total of 187 patients with primary ICH (mean age 62.4 ± 13.4 years, 67.9% male) were enrolled. 94 (50.2%) patients had small ICH. The multivariate logistic regression analysis showed an association between global SVD score and small ICH [adjusted odds ratio (aOR) 1.27, 95% CI 1.03-1.57, p = 0.027] and a trend of higher global SVD score towards non-lobar small ICH (aOR 1.23, 95% CI 0.95-1.58, p = 0.122). In the multivariate linear regression analysis, global SVD score was inversely related to hematoma volume of all ICH (ß = -0.084, 95% CI -0.142 to -0.025, p = 0.005) and non-lobar ICH (ß = -0.112, 95% CI -0.186 to -0.037, p = 0.004). Lacune (ß = -0.245, 95% CI -0.487 to -0.004, p = 0.046) was associated with lower non-lobar ICH volume. Conclusion: Global SVD score is associated with small ICH and inversely correlated with hematoma volume. This finding predominantly exists in non-lobar ICH.

Genetic screening for hypertension and COVID-19 reveals functional variation of SPEG potentially associated with severe COVID-19 in women.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to more than 6.4 million deaths worldwide. The prevalent comorbidity between hypertension and severe COVID-19 suggests common genetic factors may affect the outcome of both diseases. As both hypertension and severe COVID-19 demonstrate sex-biased prevalence, common genetic factors between the two diseases may display sex-biased differential associations. By evaluating COVID-19 association signals of 172-candidate hypertension single nucleotide polymorphisms (SNPs) derived from more than 1 million European individuals in two sex-stratified severe COVID-19 genome-wide association studies from UK BioBank with European ancestry, we revealed one functional cis expression quantitative trait locus of SPEG (rs12474050) showing sex-biased association with severe COVID-19 in women. The risk allele rs12474050*T associates with higher blood pressure. In our study, we found it is significantly correlated with lower SPEG expression in muscle-skeletal but with higher expression in both brain cerebellum and cerebellar hemisphere. Additionally, nominal significances were detected for the association between rs12474050*T and lower SPEG expression in both heart left ventricle and atrial appendage; among these tissues, the SPEG expression is nominally significantly higher in females than in males. Further analysis revealed SPEG is mainly expressed in cardiomyocytes in heart and is upregulated upon SARS-CoV-2 infection, with significantly higher upregulation of SPEG only observed in female but not in male COVID-19 patients compared to both normal female and male individuals, suggesting upregulation of SPEG is a female-specific protective mechanism against COVID-19 induced heart damage. Taken together, our analyses suggest the involvement of SPEG in both hypertension and severe COVID-19 in women, which provides new insights for sex-biased effect of severe COVID-19 in women.

The role of carbonic anhydrase III and autophagy in type 2 diabetes with cardio-cerebrovascular disease.

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases among the elderly people. The T2DM increases the risk of cardio-cerebrovascular disease (CCD), and the main pathological change of the CCD is atherosclerosis (AS). Meanwhile, the carbonic anhydrases (CAs) are involved in the formation and progression of plaques in AS. However, the exact physiological mechanism of carbonic anhydrase III (CAIII) has not been clear yet, and there are also no correlation study between CAIII protein and T2DM with CCD. The 8-week old diabetic mice (db/db-/- mice) and wild-type mice (wt mice) were feed by a normal diet till 32 weeks, and detected the carotid artery vascular opening angle using the method of biomechanics; The changes of cerebral cortex and myocardium were watched by the ultrastructure, and the autophagy were observed by electron microscope; The tissue structure, inflammation and cell injury were observed by Hematoxylin and eosin (HE) staining; The apoptosis of cells were observed by TUNEL staining; The protein levels of CAIII, IL-17, p53 were detected by immunohistochemical and Western Blot, and the Beclin-1, LC3, NF-κB were detected by Western Blot. All statistical analysis is performed using PRISM software. Compared with wt mice, db/db-/- mice' carotid artery open angle increased significantly. Electron microscope results indicated that autophagy in db/db-/- mice cerebral cortex and heart tissue decreased and intracellular organelle ultrastructure were damaged. HE staining indicated that, db/db-/- mice' cerebral cortex and heart tissue stained lighter, inflammatory cells infiltration, cell edema were obvious, myocardial fibers were disorder, and myocardial cells showed different degrees of degeneration. Compared with wt mice, TUNEL staining showed that there was obviously increase in db/db-/- mice cortex and heart tissue cell apoptosis. The results of immunohistochemistry and Western Blot indicated that CAIII, Beclin-1 and LC3II/I expression levels conspicuously decreased in cortex and heart tissue of db/db-/- mice, and the expression level of IL-17, NF-κB and p53 obviously increased. The carotid artery' vascular stiffness was increased and which was probably related with formation of AS in diabetic mice. And the autophagy participated in the occurrence and development of diabetic CCD. CAIII protein might somehow be involved in the regulation of autophagy probably through affecting cell apoptosis and inflammation, but the underlying mechanism remains to be further studied.

Protein post-translational modifications after spinal cord injury.

Deficits in intrinsic neuronal capacities in the spinal cord, a lack of growth support, and suppression of axonal outgrowth by inhibitory molecules mean that spinal cord injury almost always has devastating consequences. As such, one of the primary targets for the treatment of spinal cord injury is to develop strategies to antagonize extrinsic or intrinsic axonal growth-inhibitory factors or enhance the factors that support axonal growth. Among these factors, a series of individual protein level disorders have been identified during the generation of axons following spinal cord injury. Moreover, an increasing number of studies have indicated that post-translational modifications of these proteins have important implications for axonal growth. Some researchers have discovered a variety of post-translational modifications after spinal cord injury, such as tyrosination, acetylation, and phosphorylation. In this review, we reviewed the post-translational modifications for axonal growth, functional recovery, and neuropathic pain after spinal cord injury, a better understanding of which may elucidate the dynamic change of spinal cord injury-related molecules and facilitate the development of a new therapeutic strategy for spinal cord injury.

Hematoma Ventricle Distance on Computed Tomography Predicts Poor Outcome in Intracerebral Hemorrhage.

OBJECTIVE: To investigate the relationship between hematoma ventricle distance (HVD) and clinical outcome in patients with intracerebral hemorrhage (ICH). METHODS: We prospectively enrolled consecutive patients with ICH in a tertiary academic hospital between July 2011 and April 2018. We retrospectively reviewed images for all patients receiving a computed tomography (CT) within 6 h after onset of symptoms and at least one follow-up CT scan within 36 h. The minimum distance of hematoma border to nearest ventricle was measured as HVD. Youden index was used to evaluate the cutoff of HVD predicting functional outcome. Logistic regression model was used to assess the HVD data and clinical poor outcome (modified Rankin Scale 4-6) at 90 days. RESULTS: A total of 325 patients were included in our final analysis. The median HVD was 2.4 mm (interquartile range, 0-5.7 mm), and 119 (36.6%) patients had poor functional outcome at 3 months. After adjusting for age, admission Glasgow coma scale, intraventricular hemorrhage, baseline ICH volume, admission systolic blood pressure, blood glucose, hematoma expansion, withdrawal of care, and hypertension, HVD ≤ 2.5 mm was associated with increased odds of clinical poor outcome [odd ratio, 3.59, (95%CI = 1.72-7.50); p = 0.001] in multivariable logistic regression analysis. CONCLUSION: Hematoma ventricle distance allows physicians to quickly select and stratify patients in clinical trials and thereby serve as a novel and useful addition to predict ICH prognosis.

Intraventricular Hemorrhage Growth: Definition, Prevalence and Association with Hematoma Expansion and Prognosis.

BACKGROUND/OBJECTIVES: The objective of this study is to propose a definition of intraventricular hemorrhage (IVH) growth and to investigate whether IVH growth is associated with ICH expansion and functional outcome. METHODS: We performed a prospective observational study of ICH patients between July 2011 and March 2017 in a tertiary hospital. Patients were included if they had a baseline CT scan within 6 h after onset of symptoms and a follow-up CT within 36 h. IVH growth was defined as either any newly occurring intraventricular bleeding on follow-up CT scan in patients without baseline IVH or an increase in IVH volume ≥ 1 mL on follow-up CT scan in patients with initial IVH. Poor outcome was defined as modified Rankin Scale score of 3-6 at 90 days. The association between IVH growth and functional outcome was assessed by using multivariable logistic regression analysis. RESULTS: IVH growth was observed in 59 (19.5%) of 303 patients. Patients with IVH growth had larger baseline hematoma volume, higher NIHSS score and lower GCS score than those without. Of 44 patients who had concurrent IVH growth and hematoma growth, 41 (93.2%) had poor functional outcome at 3-month follow-up. IVH growth (adjusted OR 4.15, 95% CI 1.31-13.20; P = 0.016) was an independent predictor of poor functional outcome (mRS 3-6) at 3 months in multivariable analysis. CONCLUSION: IVH growth is not uncommon and independently predicts poor outcome in ICH patients. It may serve as a promising therapeutic target for intervention.

Activating PPARγ Increases NQO1 and γ-GCS Expression via Nrf2 in Thrombin-activated Microglia.

The present study aimed to explore the molecular mechanisms underlying the increase of nicotinamide adenine dinucleotide phosphate:quinine oxidoreductase 1 (NQO1) and γ-glutamylcysteine synthetase (γ-GCS) in brain tissues after intracerebral hemorrhage (ICH). The microglial cells obtained from newborn rats were cultured and then randomly divided into the normal control group (NC group), model control group (MC group), rosiglitazone (RSG) intervention group (RSG group), retinoic-acid intervention group (RSG+RA group), and sulforaphane group (RSG+SF group). The expression levels of NQO1, γ-GCS, and nuclear factor E2-related factor 2 (Nrf2) were measured by real-time polymerase chain reaction (RT-PCR) and Western blotting, respectively. The results showed that the levels of NQO1, γ-GCS and Nrf2 were significantly increased in the MC group and the RSG group as compared with those in the NC group (P<0.01). They were found to be markedly decreased in the RSG+RA group and increased in the RSG+SF group when compared with those in the MC group or the RSG group (P<0.01). The RSG+SF group displayed the highest levels of NQO1, γ-GCS, and Nrf2 among the five groups. In conclusion, a medium dose of RSG increased the anti-oxidative ability of thrombin-activated microglia by increasing the expression of NQO1 and γ-GCS. The molecular mechanisms underlying the increase of NQO1 and γ-GCS in thrombin-activated microglia may be associated with the activation of Nrf2.

Benign Intracerebral Hemorrhage: A Population at Low Risk for Hematoma Growth and Poor Outcome.

Background To define benign intracerebral hemorrhage ( ICH ) and to investigate the association between benign ICH , hematoma expansion, and functional outcome. Methods and Results We analyzed a prospectively collected cohort of patients with ICH, who presented within 6 hours of symptom onset between July 2011 and February 2017 to a tertiary teaching hospital. Follow-up computed tomographic scanning was performed within 36 hours after initial computed tomographic scanning. Benign ICH was operationally defined as homogeneous and regularly shaped small ICH . The presence of benign ICH was judged by 2 independent reviewers (Q.L., W.Y.) on the basis of the admission computed tomographic scan. Functional independence was defined as a modified Rankin Scale score of 0 to 2 at 3 months. The associations between benign ICH , hematoma expansion, and functional outcome were assessed by using multivariable logistic regression analyses. A total of 288 patients with ICH were included. Benign ICH was found in 48 patients (16.7%). None of the patients with benign ICH had early hematoma expansion. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of benign ICH for predicting functional independence at 3 months were 30.7%, 96.6%, 90.0%, 60.0%, and 0.637, respectively. Conclusions Patients with benign ICH are at low risk of hematoma expansion and poor outcome. These patients may be safe for less intensive monitoring and are unlikely to benefit from therapies aimed at preventing ICH expansion.

Apolipoprotein E Gene Polymorphisms Are Risk Factors for Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-analysis.

Intracerebral hemorrhage (ICH) is a serious clinical disease with high morbidity, whose pathogenesis might be related to apolipoprotein E (APOE) gene polymorphisms. To comprehensively evaluate the risk factors for ICH occurrence, we performed a meta-analysis. We searched online databases to identify eligible studies based on the relationship between APOE genetic polymorphisms and ICH occurrence risk. Specific and pooled odds ratios (ORs) were calculated and by assessing small study bias, we drew the relationship between APOE polymorphisms and ICH risk. We included 15 eligible studies in our study containing a total of 1642 ICH samples and 5545 normal controls. The comparison of ɛ4 and ɛ3 APOE genotypes revealed that specific and pooled ORs showed a significantly increased odds ratio in ICH patients with the ɛ4 genotype, indicating that ɛ4 gene is a risk factor for ICH occurrence, and the heterogeneity is acceptable. Similarly, it was found that the ɛ2 genotype also contributed to the incidence rate of ICH. However, after the subgroup analysis by ethnicity, this APOE genetic polymorphism acted as a harmful factor only in white populations, but did not show an effect in Asian populations. It was suggested that both ε2 and ε4 APOE alleles were risk factors for ICH in general. They were risk factors in white populations only, neither had a detectable effect in Asian populations after subgroup analysing by ethnicity.

Expansion-Prone Hematoma: Defining a Population at High Risk of Hematoma Growth and Poor Outcome.

BACKGROUND: Noncontrast computed tomography (CT) markers are increasingly used for predicting hematoma expansion. The aim of our study was to investigate the predictive value of expansion-prone hematoma in predicting hematoma expansion and outcome in patients with intracerebral hemorrhage (ICH). METHODS: Between July 2011 and January 2017, ICH patients who underwent baseline CT scan within 6 h of symptoms onset and follow-up CT scan were recruited into the study. Expansion-prone hematoma was defined as the presence of one or more of the following imaging markers: blend sign, black hole sign, or island sign. The diagnostic performance of blend sign, black hole sign, island sign, and expansion-prone hematoma in predicting hematoma expansion was assessed. Predictors of hematoma growth and poor outcome were analyzed using multivariable logistical regression analysis. RESULTS: A total of 282 patients were included in our final analysis. Of 88 patients with early hematoma growth, 69 (78.4%) had expansion-prone hematoma. Expansion-prone hematoma had a higher sensitivity and accuracy for predicting hematoma expansion and poor outcome when compared with any single imaging marker. After adjustment for potential confounders, expansion-prone hematoma independently predicted hematoma expansion (OR 28.33; 95% CI 12.95-61.98) and poor outcome (OR 5.67; 95% CI 2.82-11.40) in multivariable logistic model. CONCLUSION: Expansion-prone hematoma seems to be a better predictor than any single noncontrast CT marker for predicting hematoma expansion and poor outcome. Considering the high risk of hematoma expansion in these patients, expansion-prone hematoma may be a potential therapeutic target for anti-expansion treatment in future clinical studies.

Incidence and risk of thromboembolism associated with bevacizumab in patients with non-small cell lung carcinoma.

BACKGROUND: Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), is effective for the treatment of advanced non-small cell lung cancer (NSCLC). However, severe adverse events (AEs) have been reported in NSCLC patients treated with bevacizumab. Currently, the contribution of Bevacizumab to thromboembolism is still controversial. We conducted a study to determine the overall risk and incidence of thromboembolism with bevacizumab in NSCLC patients. METHODS: Electronic databases such as the PubMed, Web of Science and Cochrane Library were searched for related trials. Statistical analyses were conducted to calculate the overall incidence rates, odds ratios (ORs), and 95% confidence intervals (CIs) by using either random-effect or fixed-effect models depending on the heterogeneity. We also used trial sequence analysis (TSA) to verify the pooled result. RESULTS: A total of 3,555 subjects from nine studies were included. The overall incidence of thromboembolism events in NSCLC patients treated with bevacizumab was 4.8% (95% CI: 1.9-7.7%). Without bevacizumab, this incidence was 2.9% (95% CI: 0.6-5.1%). Bevacizumab use was associated with a significantly increased risk in thromboembolism events (OR =1.74; 95% CI: 1.15-2.62; P=0.008). Subgroup analysis based on the doses showed that bevacizumab administered at 15 mg/kg (OR =1.81; 95% CI: 1.14-2.86; P=0.012), but not 7.5 mg/kg (OR =1.32; 95% CI: 0.78-2.24; P=0.296), increased the risk of thromboembolism. CONCLUSIONS: Bevacizumab is associated with a significantly increased risk of thromboembolism development in NSCLC patients. It may have dose-toxicity relationship and low dose of bevacizumab may be a better choice for NSCLC patients, with equal efficacy and low hazard of thromboembolism events.

EGb761 improves the cognitive function of elderly db/db-/- diabetic mice by regulating the beclin-1 and NF-κB signaling pathways.

To assess whether EGb761 could protect elderly diabetic mice with cognitive disorders and explore the role of beclin-1-mediated autophagy in these protective effects. Two-month-old male db/db-/- mice and wild-type C57/BL6 mice were randomly divided into six groups: db/db-/- control, db/db-/- 50 mg, db/db-/- 100 mg, wild-type (WT) control, WT 50 mg, and WT 100 mg. EGb761 (50 mg/kg or 100 mg/kg of bodyweight) was given by gavage once a day for 1 month from the age of 6 months. Y-maze and social choice tests were performed at 8th months. The blood pressure was measured. The imaging changes in the brain were measured using magnetic resonance imaging (MRI). The expression and distribution of beclin-1, LC3, and NF-κB were detected using immunohistochemistry staining and western blotting. Ultrastructure alterations in the hippocampus were observed using transmission electron microscopy. Compared with WT mice, the learning ability, memory and overall cognitive function of db/db-/- mice decreased (P < 0.05), and EGb761 could significantly improve the learning and memory function of db/db-/- mice (P < 0.05). EGb761 significantly improved systolic blood pressure in db/db-/- mice (P < 0.01). In addition, fMRI-bold showed a decline in the hippocampus of mice in the db/db-/- group compared with WT. EGb761 could improve these above changes. Immunohistochemistry staining and western blotting confirmed that EGb761 significantly increased beclin-1 and reduced LC3-II/I levels in the brains of db/db-/- mice (P < 0.05). NF-κB levels were obviously higher in the db/db-/- group than that in the WT group, and EGb761 significantly reduced NF-κB levels in db/db-/- mice (P < 0.05). There was a trend of increased autophagosomes in db/db-/- mice, but EGb761 did not change obviously the number of autophagosomes. Compared with normal aged WT mice, aging db/db-/- mice had more common complications of cerebral small vessel disease and cognitive dysfunction. EGb761 could significantly improve the cognitive function of aging db/db-/- mice via a mechanism that may involve the regulation of beclin-1, LC3, and NF-κB.

G-CSF and cognitive dysfunction in elderly diabetic mice with cerebral small vessel disease: Preventive intervention effects and underlying mechanisms.

AIMS: Although cognitive dysfunction is a common neurological complication in elderly patients with diabetes, the mechanisms underlying this relationship remain unclear, and effective preventive interventions have yet to be developed. Thus, this study investigated the preventive effects and mechanisms of action associated with granulocyte colony-stimulating factor (G-CSF) on cognitive dysfunction in elderly diabetic mice with cerebral small vessel disease. METHODS: This study included 40 male db/db diabetic and wild-type (WT) mice that were categorized into the following four groups at the age of 3 weeks: db/db group (DG), db/db+G-CSF group (DGG), WT group (WG), and WT+G-CSF group (WGG). The mice were fed normal diets for 4 months and then given G-CSF (75 µg/kg) via intraperitoneal injections for 1 month. At 7.5 months of age, the cognitive abilities of the mice were assessed with the Y-maze test and the Social Choice Test; body weight, blood pressure (BP), and blood glucose measurements were obtained throughout the study. Brain imaging and blood oxygen level-dependent (BOLD) contrast imaging analyses were performed with a small animal magnetic resonance imaging (MRI) system, autophagosome levels were detected with a transmission electron microscope (TEM), hippocampal neurons were assessed with hematoxylin and eosin (HE) staining, and protein expressions and distributions were evaluated using immunohistochemistry and Western blot analyses. RESULTS: (i) The body weight and blood glucose levels of the DG and DGG mice were significantly higher than those of the WG and WGG mice; (ii) social choice and spatial memory capabilities were significantly reduced in DG mice but were recovered by G-CSF in DGG mice; (iii) the MRI scans revealed multiple lacunar lesions and apparent hippocampal atrophy in the brains of DG mice, but G-CSF reduced the number of lacunar lesions and ameliorated hippocampal atrophy; (iv) the MRI-BOLD scans showed a downward trend in whole-brain activity and reductions in the connectivities of the hippocampus and amygdala with subcortical structures in DG mice, but G-CSF clearly improved the altered brain activity as well as the connectivity of the hippocampus in DGG mice; (v) HE staining revealed fewer neurons in the hippocampus in DG mice; (vi) TEM analyses revealed significantly fewer autophagosomes in the hippocampi of DG mice, but G-CSF did not increase these numbers; (vii) there were significant reductions in mechanistic target of rapamycin (mTOR) and LC3-phosphatidylethanolamine conjugate (LC3)-II/I levels in the hippocampi of DG mice, whereas p62 was upregulated, and G-CSF significantly enhanced the levels of Beclin1, mTOR, and LC-II/I in DGG mice; and (viii) G-CSF significantly reversed increases in nuclear factor κB (NF-κB) protein levels in DG but not in WG mice. CONCLUSIONS: In this study, aged diabetic mice were prone to cognitive dysfunction and cerebral small vessel disease. However, administration of G-CSF significantly improved cognitive function in elderly db/db diabetic mice, and this change was likely related to the regulation of autophagy and NF-κB signaling pathways.

[Degradation Characteristics of Spectral Analysis of Straw Nursery Containers in Situ Soil Culture].

This paper aimed to reveal the degradation behavior of a new type of biodegradable containers. The biodegradable containers, which was made of modified soybean adhesive and straw, was processed in situ biodegradation under natural condition. The physicochemical property and microstructure of straw nursery containers treated and untreated were characterized with Cellulose Tester, Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscope - Energy Dispersive X-ray Spectroscopy (SEM-EDS), and Thermo-gravimetry Analysis (TGA), respectively. The results indicated that the content of cellulose, hemicellulose and lignin of treated specimen decreased to 21.43%, 21.41% and 9.54% from 29.03%, 30.44% and 12.52%, respectively, comparing with those of untreated straw nursery container. FTIR analysis revealed that the ester and fat bond have been ruptured, and the aromatic characteristic peak became weakened. SEM-EDS spectrum showed the microfibril chain in the container has been fragmentation, and the soybean adhesive was also degradation. The surface of container appeared oxidization degradation. TGA analysis showed that a large number of small molecules have been produced in the process of degradation and the thermo-stability of treated samples improved.