Elucidating the mechanism of action of Radix Angelica sinensis (Oliv.) Diels and Radix Astragalus mongholicus Bunge ultrafiltration extract on radiation-induced myocardial fibrosis based on network pharmacology and experimental research.

Myocardial fibrosis can induce cardiac dysfunction and remodeling. Great attention has been paid to traditional chinese medicine (TCM) 's effectiveness in treating MF. Radix Angelica sinensis (Oliv.) Diels and Radix Astragalus mongholicus Bunge ultrafiltration extract (RAS-RA), which is a key TCM compound preparation, have high efficacy in regulating inflammation. However, studies on its therapeutic effect on radiation-induced myocardial fibrosis (RIMF) are rare. In this study, RAS-RA had therapeutic efficacy in RIMF and elucidated its mechanism of action. First, we formulated the prediction network that described the relation of RAS-RA with RIMF according to data obtained in different databases. Then, we conducted functional enrichment to investigate the functions and pathways associated with potential RIMF targets for RAS-RA. In vivo experiments were also performed to verify these functions and pathways. Second, small animal ultrasound examinations, H&E staining, Masson staining, transmission electron microscopy, Enzyme-linked immunosorbent assay (ELISA), Western-blotting, Immunohistochemical method and biochemical assays were conducted to investigate the possible key anti-RIMF pathway in RAS-RA. In total, 440 targets were detected in those 21 effective components of RAS-RA; meanwhile, 1,646 RIMF-related disease targets were also discovered. After that, PPI network analysis was conducted to identify 20 key targets based on 215 overlap gene targets. As indicated by the gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis results, inflammation and PI3K/AKT/mTOR pathways might have important effects on the therapeutic effects on RIMF. Molecular docking analysis revealed high binding of effective components to targets (affinity < -6 kcal/mol). Based on experimental verification results, RAS-RA greatly mitigated myocardial fibrosis while recovering the cardiac activity of rats caused by X-rays. According to relevant protein expression profiles, the PI3K/AKT/mTOR pathway was important for anti-fibrosis effect of RAS-RA. Experimental studies showed that RAS-RA improved cardiac function, decreased pathological damage and collagen fiber deposition in cardiac tissues, and improved the mitochondrial structure of the heart of rats. RAS-RA also downregulated TNF-α, IL-6, and IL-1ß levels. Additionally, RAS-RA improved the liver and kidney functions and pathological injury of rat kidney and liver tissues, enhanced liver and kidney functions, and protected the liver and kidneys. RAS-RA also increased PI3K, AKT and mTOR protein levels within cardiac tissues and downregulated α-SMA, Collagen I, and Collagen III. The findings of this study suggested that RAS-RA decreased RIMF by suppressing collagen deposition and inflammatory response by inhibiting the PI3K/AKT/mTOR pathway. Thus, RAS-RA was the potential therapeutic agent used to alleviate RIMF.

Therapeutic potential of Angelica sinensis in addressing organ fibrosis: A comprehensive review.

Fibrosis-related diseases (FRD) include conditions like myocardial fibrosis, pulmonary fibrosis, hepatic fibrosis, renal fibrosis, and others. The impact of fibrosis can be severe, causing organ dysfunction, reduced functionality, and even organ failure, leading to significant health issues. Currently, there is a lack of effective modern anti-fibrosis drugs in clinical practice. However, Chinese medicine has a certain beneficial effect on the treatment of such diseases. Angelica sinensis, with its considerable medicinal value, has garnered attention for its anti-fibrosis properties in recent investigations. In the past few years, there has been a growing number of experimental inquiries into the impact of angelica polysaccharide (ASP), angelica water extract, angelica injection, and angelica compound preparation on fibrosis-associated ailments, piquing the interest of researchers. This paper aims to consolidate recent advances in the study of Angelica sinensis for the treatment of fibrosis-related disorders, offering insights for prospective investigations. Literature retrieval included core electronic databases, including Baidu Literature, CNKI, Google-Scholar, PubMed, and Web of Science. The applied search utilized specified keywords to extract relevant information on the pharmacological and phytochemical attributes of plants. The investigation revealed that Angelica sinensis has the potential to impede the advancement of fibrotic diseases by modulating inflammation, oxidative stress, immune responses, and metabolism. ASP, Angelica sinensis extract, Angelica sinensis injection, and Angelica sinensis compound preparation were extensively examined and discussed. These constituents demonstrated significant anti-fibrosis activity. In essence, this review seeks to gain a profound understanding of the role of Angelica sinensis in treating fiber-related diseases. Organ fibrosis manifests in nearly all tissues and organs, posing a critical challenge to global public health due to its widespread occurrence, challenging early diagnosis, and unfavorable prognosis. Despite its prevalence, therapeutic options are limited, and their efficacy is constrained. Over the past few years, numerous studies have explored the protective effects of traditional Chinese medicine on organ fibrosis, with Angelica sinensis standing out as a multifunctional natural remedy. This paper provides a review of organ fibrosis pathogenesis and summarizes the recent two decades' progress in treating fibrosis in various organs such as the liver, lung, kidney, and heart. The review highlights the modulation of relevant signaling pathways through multiple targets and channels by the effective components of Angelica sinensis, whether used as a single medicine or in compound prescriptions.

Analogous Confinement Effect Enables High Stability and High Capacity Ammonium Storage in Polyaniline@Poly(o-fluoroaniline)@Carbon Layer.

Rechargeable aqueous ammonium ion (NH4 + ) batteries have attracted much attention due to the unique properties of NH4 + . Polyaniline (PA) with outstanding conductivity is a potential cathode material, but it can be oxidized to pernigraniline (PG) rapidly, resulting in its poor stability. In this study, polyaniline@poly(o-fluoroaniline)@carbon layer (PA@POFA@C) is prepared for excellent and durable NH4 + storage. PA@POFA@C exhibits a high capacity of 208 mAh g-1 at 0.2 A g-1 and maintains 126 mAh g-1 at 10 A g-1 . More importantly, an excellent capacity retention rate of 88.24% is achieved after 2000 cycles with ≈100% coulombic efficiency. Spectroscopy studies suggest analogous confinement effect can effectively limit the escape of hydrogen in imine group, and form the hydrogen-restricted region between the PA and POFA layer which can provide H+ for the complete reduction of PG. Meanwhile, the hydrophobic effect of POFA effectively restrains the hydrolysis of PG. Interestingly, the introduction of C layer improves the hydrophilicity of electrode and shortens the activation process, serving as the outermost protective layer of the electrode. Finally, PA@POFA@C achieves desirable electrochemical performances with analogous confinement effect. This research provides ideas for the preparation of advanced polymer electrodes for aqueous NH4 + batteries.

Development and validation of a nomogram to predict cardiac death after radiotherapy for esophageal cancer.

Background: Patients frequently die from cardiac causes after radiotherapy for esophageal cancer. Early detection of cardiac death risk in these patients is crucial to improve clinical decision-making and prognosis. Thus, we modeled the risk of cardiac death after irradiation for esophageal cancer. Methods: A retrospective analysis of 37,599 esophageal cancer cases treated with radiotherapy in the SEER database between 2000 and 2018 was performed. The selected cases were randomly assigned to the model development group (n = 26,320) and model validation group (n = 11,279) at a ratio of 7:3. We identified the risk factors most commonly associated with cardiac death by least absolute shrinkage and selection operator regression analysis (LASSO). The endpoints for model development and validation were 5- and 10-year survival rates. The net clinical benefit of the models was evaluated by decision curve analysis (DCA) and concordance index (C-index). The performance of the models was further assessed by creating a receiver operating characteristic curve (ROC) and calculating the area under the curve (AUC). Kaplan-Meier (K-M) survival analysis was performed on the probability of death. Patients were classified according to death probability thresholds. Five- and ten-year survival rates for the two groups were shown using K-M curves. Results: The major risk factors for cardiac death were age, surgery, year of diagnosis, sequence of surgery and radiotherapy, chemotherapy and a number of tumors, which were used to create the nomogram. The C-indexes of the nomograms were 0.708 and 0.679 for the development and validation groups, respectively. DCA showed the good net clinical benefit of nomograms in predicting 5- and 10-year risk of cardiac death. The model exhibited moderate predictive power for 5- and 10-year cardiac mortality (AUC: 0.833 and 0.854, respectively), and for the development and validation cohorts (AUC: 0.76 and 0.813, respectively). Conclusions: Our nomogram may assist clinicians in making clinical decisions about patients undergoing radiotherapy for esophageal cancer based on early detection of cardiac death risk.

Development and Validation of a Nomogram Model for the Risk of Cardiac Death in Patients Treated with Chemotherapy for Esophageal Cancer.

The primary cause of mortality in esophageal cancer survivors is cardiac death. Early identification of cardiac mortality risk during chemotherapy for esophageal cancer is crucial for improving the prognosis. We developed and validated a nomogram model to identify patients with high cardiac mortality risk after chemotherapy for esophageal cancer for early screening and clinical decision-making. We randomly allocated 37,994 patients with chemotherapy-treated esophageal cancer into two groups using a 7:3 split ratio: model training (n = 26,598) and validation (n = 11,396). 5- and 10-year survival rates were used as endpoints for model training and validation. Decision curve analysis and the consistency index (C-index) were used to evaluate the model's net clinical advantage. Model performance was evaluated using receiver operating characteristic curves and computing the area under the curve (AUC). Kaplan-Meier survival analysis based on the prognostic index was performed. Patient risk was stratified according to the death probability. Age, surgery, sex, and year were most closely related to cardiac death and used to plot the nomograms. The C-index for the training and validation datasets were 0.669 and 0.698, respectively, indicating the nomogram's net clinical advantage in predicting cardiac death risk at 5 and 10 years. The 5- and 10-year AUCs were 0.753 and 0.772 for the training dataset and 0.778 and 0.789 for the validation dataset, respectively. The accuracy of the model in predicting cardiac death risk was moderate. This nomogram can identify patients at risk of cardiac death after chemotherapy for esophageal cancer at an early stage.

Pharmacological action of Hedysarum polysaccharides: a review.

Hedysarum, a traditional Chinese herbal medicine and food with a long history of clinical application, is used to improve health conditions and treat various diseases. Hedysarum polysaccharides (HPS), flavonoids, saponins, and alkaloids, are the primary components of Hedysarum. HPS is the most important natural active ingredient of Hedysarum, which has many pharmacological effects. Currently, HPS exhibits significant promise in drug development for various ailments such as tumors, diabetes, cardiovascular diseases, Alzheimer's disease, and fibrosis. This review paper discusses the extraction, separation, and content determination techniques of HPS, along with the investigation of its chemical constituents. More importantly, we reviewed the anti-inflammatory pharmacological effects of HPS, such as inhibition of inflammatory factors and NF-κB signaling pathway; antitumor activity through apoptosis induction in tumor cells and blocking tumor cell proliferation and metastasis; antioxidant effects; regulation of various cytokines and immune cells; regulation of blood sugar levels, such as in type I and type II diabetes and in diabetic complications; improvement in symptoms of Alzheimer disease; anti-aging and anti-fibrosis properties; and improvement in cerebral ischemia-reperfusion injury. This review paper establishes the theoretical foundation for future studies on the structure, mechanism, and clinical use of HPS.

Early diagnostic value of high-sensitivity cardiac troponin T for cancer treatment-related cardiac dysfunction: a meta-analysis.

Early diagnosis of cancer treatment-related cardiac dysfunction (CTRCD) is important as cancer therapy increases the risk of cardiac dysfunction. High-sensitivity cardiac troponin T (hs-cTnT) is a highly specific marker of myocardial injury. However, its diagnostic value for CTRCD has not been systematically evaluated. This meta-analysis aimed to evaluate whether hs-cTnT could be used as an early diagnostic biomarker for CTRCD. We systematically surveyed PubMed, Embase, Cochrane Library, and Web of Science databases for studies of hs-cTnT for the diagnosis of CTRCD before 1 April 2022. Patients of all ages and all cancer types who underwent echocardiographic left ventricular ejection fraction assessment and blood hs-cTnT and received anticancer therapy (including chemotherapy, radiotherapy, targeted therapy, immune checkpoint inhibitors, and other treatments) were included in this study, resulting in a total of eight studies with 1294 patients. The occurrence of CTRCD was associated with elevated hs-cTnT [sensitivity: 0.78, 95% confidence interval (CI): 0.64-0.88; specificity: 0.75, 95% CI: 0.59-0.86; area under the curve (AUC): 0.83, 95% CI: 0.80-0.86]. We further performed subgroup analysis and found that the AUC of hs-cTnT elevation for the diagnosis of CTRCD increased from 0.83 to 0.90 (95% CI: 0.87-0.92) at 3-6 months, suggesting a higher early diagnostic value of hs-cTnT compared with echocardiography for CTRCD. In terms of clinical applicability, the Fagan plot showed pre-test and post-test probabilities of 51% and 9%, respectively, indicating that hs-cTnT testing can improve the accuracy of clinical diagnosis of CTRCD. However, it was not possible to determine the optimal cut-off value for early diagnosis of CTRCD with hs-cTnT. The Deeks funnel plot was largely symmetrical (P = 0.74); hence, publication bias was not observed. Hs-cTnT allowed early CTRCD diagnosis at 3-6 months. However, further high-quality research is needed to determine the optimal cut-off value for early CTRCD diagnosis with this biomarker.

Research progress of natural medicine Astragalus mongholicus Bunge in treatment of myocardial fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial fibrosis (MF) is a common pathological manifestation of many cardiovascular diseases at a certain stage, with excessive accumulation of collagen fibers, excessive increase in collagen content, and a significant increase in collagen volume as the main pathological changes. There are currently no effective drugs for the treatment of myocardial fibrosis. Traditional Chinese medicine (TCM), the main component of the medical practice used for more than 5000 years, especially in China, often exerts a wider action spectrum than previously attempted options in treating human diseases. In recent times, the great potential of TCM in the treatment of MF has received much attention. Especially many experimental studies on the treatment of MF by Astragalus mongholicus Bunge have been conducted, and the effect is remarkable, which may provide more comprehensive database and theoretical support for the application of Astragalus mongholicus Bunge in the treatment of MF and could be considered a promising candidate drug for preventing MF. AIM OF THE REVIEW: This review summarizes the chemical components of Astragalus mongholicus Bunge, Astragalus mongholicus Bunge extract, Astragalus mongholicus Bunge single prescription, and Astragalus mongholicus Bunge compound preparation in the treatment of MF, and provides comprehensive information and a reliable basis for the exploration of new treatment strategies of botanical drugs in the therapy of MF. METHODS: The literature information was obtained from the scientific databases on ethnobotany and ethnomedicines (up to August 2022), mainly from the PubMed, Web of Science, and CNKI databases. The experimental studies on the anti-myocardial fibrosis role of the effective active components of Astragalus mongholicus Bunge and the utility of its compound preparation and the involved mechanisms were identified. The search keywords for such work included: "myocardial fibrosis" or "Cardiac fibrosis ", and "Astragalus mongholicus Bunge", "extract," or "herb". RESULTS: Several studies have shown that the effective active components of Astragalus mongholicus Bunge and its formulas, particularly Astragaloside IV, Astragalus polysaccharide, total saponins of Astragalus mongholicus Bunge, triterpenoid saponins of Astragalus mongholicus Bunge, and cycloastragenol, exhibit potential benefits against MF, the mechanisms of which appear to involve the regulation of inflammation, oxidant stress, and pro-fibrotic signaling pathways, etc. Conclusion: These research works have shown the therapeutic benefits of Astragalus mongholicus Bunge in the treatment of MF. However, further research should be undertaken to clarify the unconfirmed chemical composition and regulatory mechanisms, conduct standard clinical trials, and evaluate the possible side effects. The insights in the present review provided rich ideas for developing new anti-MF drugs. THESIS: Myocardial fibrosis (MF) with excessive accumulation of collagen fibers, excessive increase in collagen content, and a significant increase in collagen volume as the main pathological changes is a common pathological manifestation of many cardiovascular diseases at a certain stage, which seriously affects cardiac function. At present, there is still a lack of effective drugs for the treatment of MF. Traditional Chinese medicine (TCM), the main component of the medical practice used for more than 5000 years especially in China, often exerts wider action spectrum than previously attempted options in treating human diseases. In recent times, the great potential of TCM in the treatment of MF has received much attention. Especially many experimental studies on the treatment of MF by Astragalus mongholicus Bunge have been conducted, and the effect is remarkable, which may provide more comprehensive data base and theoretical support for the application of Astragalus mongholicus Bunge in the treatment of MF and could be considered a promising candidate drug for preventing MF.

Role and molecular mechanism of traditional Chinese medicine in preventing cardiotoxicity associated with chemoradiotherapy.

Cardiotoxicity is a serious complication of cancer therapy. It is the second leading cause of morbidity and mortality in cancer survivors and is associated with a variety of factors, including oxidative stress, inflammation, apoptosis, autophagy, endoplasmic reticulum stress, and abnormal myocardial energy metabolism. A number of studies have shown that traditional Chinese medicine (TCM) can mitigate chemoradiotherapy-associated cardiotoxicity via these pathways. Therefore, this study reviews the effects and molecular mechanisms of TCM on chemoradiotherapy-related cardiotoxicity. In this study, we searched PubMed for basic studies on the anti-cardiotoxicity of TCM in the past 5 years and summarized their results. Angelica Sinensis, Astragalus membranaceus Bunge, Danshinone IIA sulfonate sodium (STS), Astragaloside (AS), Resveratrol, Ginsenoside, Quercetin, Danggui Buxue Decoction (DBD), Shengxian decoction (SXT), Compound Danshen Dripping Pill (CDDP), Qishen Huanwu Capsule (QSHWC), Angelica Sinensis and Astragalus membranaceus Bunge Ultrafiltration Extract (AS-AM),Shenmai injection (SMI), Xinmailong (XML), and nearly 60 other herbs, herbal monomers, herbal soups and herbal compound preparations were found to be effective as complementary or alternative treatments. These preparations reduced chemoradiotherapy-induced cardiotoxicity through various pathways such as anti-oxidative stress, anti-inflammation, alleviating endoplasmic reticulum stress, regulation of apoptosis and autophagy, and improvement of myocardial energy metabolism. However, few clinical trials have been conducted on these therapies, and these trials can provide stronger evidence-based support for TCM.

Finite element comparative analysis of three different internal fixation methods in the treatment of Pauwels type III femoral neck fractures.

BACKGROUND: Comparison of 4 cannulated lag screws (3 inverted triangular cannulated screws + anti-rotating screws;4 CLS), dynamic hip screws + derotational screws (DHS + DS), and femoral neck fixation system (FNS) in the treatment of Biomechanical properties of middle-aged Pauwels type III femoral neck fractures. METHODS: The femur CT data of a healthy young volunteer was selected and imported into Mimics software to construct a three-dimensional model of a normal femur. Pauwels type III femoral neck fractures were simulated according to the 70° fracture line. Use Geomagic and SolidWorks software to optimize and build CLS, DHS + DS, and FNS fracture internal fixation models. Finally, Ansys software was used to analyze the stress distribution, peak value, and maximum displacement of the proximal fracture fragment and internal fixation; the displacement distribution, and peak value of the fracture surface at the fracture end. RESULTS: ① The stress peaks of the proximal fracture fragments in the three groups were concentrated near the femoral calcar. The peak stress of the FNS group was the largest, and the DHS + DS group was the smallest. ②The displacement of the fracture fragments was all located at the top of the femur. The peak displacement of the FNS group was the largest, and the DHS + DS group was the smallest. ③ The internal fixation stress of the three groups is concentrated in the middle part of the device. The stress distribution of the first two groups of models is more uniform than that of FNS. The peak stress of FNS is the largest and the CLS is the smallest. ④ The internal fixed displacements are all located at the top of the model. The peak displacement of the CLS is the largest, and the DHS + DS is the smallest. ⑤ The displacement of the fracture surface is in the upper part of the fractured end. The peak displacement of the FNS group was the largest, and the DHS + DS group was the smallest. CONCLUSION: Compared with the other two internal fixation methods, dynamic hip screw + derotational screw (DHS + DS) showed good biomechanical stability. When Pauwels type III femoral neck fracture occurs in young adults, DHS + DS can be given priority as the preferred treatment for this type of fracture.

Correlation Between the MTHFR C677T Genotype and Coronary Heart Disease in Populations from Gansu, China.

This study was designed to evaluate the relationship between polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and coronary heart disease (CHD) in populations from the Gansu region of China. The MTHFR C677T polymorphism genotypes from 209 patients with CHD, as confirmed by coronary angiography, and 212 non-CHD control patients were identified using PCR gold magnetic particle chromatography. We simultaneously evaluated homocysteine (Hcy) and folate levels in these samples using biochemical methods. The TT genotype of the MTHFR C677T locus was significantly more frequent in the CHD group than in the control, while the CC genotype was significantly less frequent in CHD patients than in non-CHD patients (p < 0.05). In addition, biochemical analysis revealed that the serum Hcy levels increased, and folate levels decreased in the TT genotype. Logistic regression analysis showed that this correlation was independent of nationality, sex, age, body mass index, medical history, and blood lipid level (p < 0.05). The occurrence of the TT genotype at the MTHFR C677T locus was closely associated with CHD in the Gansu population and may serve as a biomarker of increased risk for this disease.

Research Progress of Traditional Chinese Medicine in Treatment of Myocardial fibrosis.

Effective drugs for the treatment of myocardial fibrosis (MF) are lacking. Traditional Chinese medicine (TCM) has garnered increasing attention in recent years for the prevention and treatment of myocardial fibrosis. This Article describes the pathogenesis of myocardial fibrosis from the modern medicine, along with the research progress. Reports suggest that Chinese medicine may play a role in ameliorating myocardial fibrosis through different regulatory mechanisms such as reduction of inflammatory reaction and oxidative stress, inhibition of cardiac fibroblast activation, reduction in extracellular matrix, renin-angiotensin-aldosterone system regulation, transforming growth Factor-ß1 (TGF-ß1) expression downregulation, TGF-ß1/Smad signalling pathway regulation, and microRNA expression regulation. Therefore, traditional Chinese medicine serves as a valuable source of candidate drugs for exploration of the mechanism of occurrence and development, along with clinical prevention and treatment of MF.

A multi-scale UAV image matching method applied to large-scale landslide reconstruction.

Three-dimensional (3D) sparse reconstruction of landslide topography based on unmanned aerial vehicle (UAV) images has been widely used for landslide monitoring and geomorphological analysis. In order to solve the isolated island phenomenon caused by multi-scale image matching, which means that there is no connection between the images of different scales, we herein propose a method that selects UAV image pairs based on image retrieval. In this method, sparse reconstruction was obtained via the sequential structure-from-motion (SfM) pipeline. First, principal component analysis (PCA) was used to reduce high-dimensional features to low-dimensional features to improve the efficiency of retrieval vocabulary construction. Second, by calculating the query depth threshold and discarding the invalid image pairs, we improved the efficiency of image matching. Third, the connected network of the dataset was constructed based on the initial matching of image pairs. The lost multi-scale image pairs were identified and matched through the image query between the connection components, which further improved the integrity of image matching. Our experimental results show that, compared with the traditional image retrieval method, the efficiency of the proposed method is improved by 25.9%.

Laser Spot Center Location Method for Chinese Spaceborne GF-7 Footprint Camera.

The Gaofen-7 (GF-7) satellite is equipped with two area array sensor footprint cameras to capture the laser altimeter spot. In order to establish a direct correspondence between the laser data and the stereo image data, a new method is proposed to fit the center of the spot using the brightness difference between the spot image and the footprint image. First, the geometric registration between the spot image and the footprint image is completed based on feature matching or template matching. Then, the brightness values between the two images are extracted from the corresponding image position to form a measurement, and the least squares adjustment method is used to calculate the parameters of the brightness conversion model between the spot image and the footprint image. Finally, according to the registration relationship, the center of the identified spots is respectively positioned in the footprint images, so that the laser spots are accurately identified in the along-track stereo footprint images. The experimental results show that the spot error of this method is less than 0.7 pixel, which has higher reliability and stability, and can be used for a GF-7 satellite footprint camera.

Prevalence, Risk Factors, and Complaints Screening Tool Exploration of Subjective Cognitive Decline in a Large Cohort of the Chinese Population.

BACKGROUND: Substantial studies have reported the prevalence and the affecting factors of subjective cognitive decline (SCD). The complaints screening scale has also been used for probing. However, little is known in China. OBJECTIVE: To investigate the prevalence and risk factors of SCD, and explore an SCD complaints screening scale in China. METHODS: Stratified cluster random sampling was conducted. 2,689 residents aged 60-80 years completed questionnaire 1. 814 residents were included for clinical and neuropsychological evaluations. Two standards were used to make the diagnosis of mild cognitive impairment (MCI) and SCD, and a preliminary screening rate comparison was carried out. Finally, we assessed the risk factors of SCD and the correlation between the SCD-questionnaire 9 (SCD-Q9) and the Auditory Verbal Learning Test-Long Delay Free Recall (AVLT-LR). RESULTS: 1) Standard 1 (ADNI2): the prevalence of SCD was 18.8% (95% CI = 14.7-22.9%) and zero conformed to six criteria (SCD plus). 2) Standard 2 (Jak/Bondi): the prevalence of SCD was 14.4% (95% CI = 10.7-18.1%). 3) Standard 1 had a relatively higher "false" positive rate, whereas Standard 2 had higher "false" negative rate. 4) Age, low education, fewer close friends, and daily drinking were independent risk factors for SCD progressing to MCI. 5) Total points of SCD-Q9 were negatively correlated to the value of AVLT-LR. CONCLUSIONS: The prevalence of SCD is high in the ShunYi District in Beijing, China. Age, low education, less social support, and daily drinking are independent risk factors. The brief SCD-Q9 can be used as a reference.

Dynasore Improves Motor Function Recovery via Inhibition of Neuronal Apoptosis and Astrocytic Proliferation after Spinal Cord Injury in Rats.

Spinal cord injury (SCI) is a common and devastating central nervous system insult which lacks efficient treatment. Our previous experimental findings indicated that dynamin-related protein 1 (Drp1) mediates mitochondrial fission during SCI, and inhibition of Drp1 plays a significant protective effect after SCI in rats. Dynasore inhibits GTPase activity at both the plasma membrane (dynamin 1, 2) and the mitochondria membrane (Drp1). The aim of the present study was to investigate the beneficial effects of dynasore on SCI and its underlying mechanism in a rat model. Sprague-Dawley rats were randomly assigned to sham, SCI, and 1, 10, and 30 mg dynasore groups. The rat model of SCI was established using an established Allen's model. Dynasore was administered via intraperitoneal injection immediately. Results of motor functional test indicated that dynasore ameliorated the motor dysfunction greatly at 3, 7, and 10 days after SCI in rats (P < 0.05). Results of western blot showed that dynasore has remarkably reduced the expressions of Drp1, dynamin 1, and dynamin 2 and, moreover, decreased the Bax, cytochrome C, and active Caspase-3 expressions, but increased the expressions of Bcl-2 at 3 days after SCI (P < 0.05). Notably, the upregulation of proliferating cell nuclear antigen (PCNA) and glial fibrillary acidic protein (GAFP) are inhibited by dynasore at 3 days after SCI (P < 0.05). Results of immunofluorescent double labeling showed that there were less apoptotic neurons and proliferative astrocytes in the dynasore groups compared with SCI group (P < 0.05). Finally, histological assessment via Nissl staining demonstrated that the dynasore groups exhibited a significantly greater number of surviving neurons compared with the SCI group (P < 0.05). This neuroprotective effect was dose-dependent (P < 0.05). To our knowledge, this is the first study to indicate that dynasore significantly enhances motor function which may be by inhibiting the activation of neuronal mitochondrial apoptotic pathway and astrocytic proliferation in rats after SCI.

MicroRNA-494 inhibits proliferation and metastasis of osteosarcoma through repressing insulin receptor substrate-1.

Despite microRNA-494 (miR-494) has a well-established role in many types of cancer; the biological function and potential mechanism of miR-494 in human osteosarcoma (OS) has not been elucidated. The aim of this study was therefore to investigate the role and underlying mechanism of miR-494 expression in osteosarcoma. Here, we found that miR-494 was significantly decreased in OS tissues and cell lines compared to the adjacent noncancerous bone tissues (P<0.01) and human normal osteoblast cells (NHOst) (P<0.05), respectively. Functional assays demonstrated that ectopic overexpression of miR-494 could significantly inhibit cell proliferation, colony formation, migration and invasion in vitro, as well as suppress tumor growth in nude mice model. Further integrative and functional studies suggested insulin receptor substrate 1 (IRS1) as a target gene of miR-494 in OS cells. IRS1 expression was upregulated, and inversely correlated with miR-494 expression in clinical OS tissues (r=-0.589, P=0.001). Moreover, downregulation of IRS1 had similar the inhibition effect on cell proliferation, colony formation, migration and invasion of miR-494 overexpression. Overexpresion of miR-494 obviously decreased AKT signal pathway activation. These findings suggested that miR-494 functioned as a tumor suppressor in OS, at least in part, by targeting IRS1.

Acetyl-L-carnitineameliorates mitochondrial damage and apoptosis following spinal cord injury in rats.

Acetyl-l-carnitine (ALC) facilitates the entry and exit of fatty acids from mitochondria and plays an essential role in energy metabolism. Although ALC is known to exert neuroprotective effects in multiple neurological diseases, its effects on spinal cord injury (SCI)-induced mitochondrial impairments and apoptosis remain unclear. In this study, we aimed to evaluate the putative effects of ALC on mitochondrial dysfunction and apoptosis induced by SCI in a rodent model. Our results indicate that SCI elicits dynamic alternations in the expression of mitochondria-related proteins. Transmission electron microscopy analysis showed that ALC administration abrogated key ultrastructural abnormalities in mitochondria at 24h after SCI by maintaining mitochondrial length, reducing the number of damaged mitochondria, and reversing mitochondrial score (P<0.05 compared with SCI group). In addition, ALC administration maintained the mitochondrial membrane potential and mitochondrial Na(+)-K(+)-ATPase activity following SCI (P<0.05 compared with SCI group). ALC administration reversed the downregulation of mitofusin 1 (Mfn1), Mfn2, Bcl-2, and the upregulation of dynamin-related protein 1 (Drp1), mitochondrial fission 1 (Fis1), Bcl-2-associated X protein (Bax) and cytosol cytochrome c (cyto-CytC) induced by SCI (P<0.05 compared with SCI group). Finally ALC administration greatly reduced the percentage of apoptotic cells compared with the SCI group (P<0.01). In conclusion, our findings demonstrated that ALC ameliorated SCI-induced mitochondrial structural alternations, mitochondrial dysfunction, and apoptosis.

[Effects of bone marrow mesenchymal stem cells transplantation on expression of vascular endothelial growth factor gene and angiogenesis after spinal cord injury in rats].

OBJECTIVE: To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on the motor function recovery, the expression of vascular endothelial growth factor (VEGF) gene, and angiogenesis after spinal cord injury (SCI) in rats, and to explore the treatment mechanism of BMSCs in SCI. METHODS: BMSCs were isolated and cultured from the marrow of 5 Wistar rats (4 weeks old) and the 3rd-4th passage cells were prepared for the experiment. A total of 87 adult female Wistar rats (weighing 220-250 g) were randomly divided into 3 groups: sham-operated group (group A, n=21), DMEM group (group B, n=33), BMSCs group (group C, n=33). A laminectomy was only performed at T8-10 levels in group A. The SCI models were established by modified Nystrom's compression method in groups B and C, and BMSCs and DMEM were injected in groups B and C respectively at 30 minutes after SCI. Basso-Beattie-Bresnahan (BBB) score was used for the motor function recovery at 3, 7, 14, and 28 days, RT-PCR for the VEGF mRNA at 1, 3, and 5 days, and immunohistochemical staining for angiogenesis at 3, 7, 14, and 28 days. RESULTS: In groups B and C, the hindlimb locomotor function was improved at different degrees with time, showing significant difference in BBB score between groups B, C and group A (P < 0.05). At 28 days, the BBB score in group C was significantly higher than that in group B (P < 0.05) and there was no significant difference between groups B and C (P > 0.05) at 3, 7, and 14 days after transplantation. The numbers of microvessels in the ventral horns of gray matter around SCI in groups B and C were significantly lower than that in group C (P < 0.05) at 3 days, but there was no significant difference at 7, 14, and 28 days after transplantation (P > 0.05). There was no significant difference in the number of microvessels between group C and group B (P > 0.05) at 3 and 7 days, but the number of microvessels in group C was significantly higher than that in group B (P < 0.05) at 14 and 28 days after transplantation. However, there was no significant difference in the number of microvessels in the white matter around SCI in 3 groups at different time points after transplantation (P > 0.05). The RT-PCR results showed that VEGF mRNA expressed at a low level in group A. Compared with group A, the expression level of VEGF mRNA in groups B and C increased at 1 day and reached the peak at 3 days, then decreased at 5 days after transplantation; and the expression of VEGF mRNA was significantly higher in groups B and C than in group A (P < 0.05), and in group C than in group B (P < 0.05) at 1, 3, and 5 days. CONCLUSION: BMSCs may promote the motor function recovery by up-regulating VEGF mRNA expression and increasing angiogenesis in the spinal cord after SCI in rats.

[Repair of peripheral nerve gap with the use of tissue engineering scaffold complex].

OBJECTIVE: To study the feasibility to repair the peripheral nerve gap with tissue engineering scaffold complex that is composed of medical biodegradable material agarose hydrogel and nerve growth factor (NGF). METHODS: Chitosan tube containing agarose hydrogel and NGF was transplanted to bridge a 10 mm gap of injured sciatic nerve in rat. Chitosan duct without agarose hydrogel and NGF was used as negative control, while autograft nerve as positive control. Sixteen weeks after operation, the regeneration of nerve fiber was observed with morphological and immunohistochemistrical methods. RESULT: The number and diameter of regenerating nerve fibers bridged by the scaffold complex of agarose hydrogel and NGF were better than negative control group (P < 0.01) and reached the level of autograft nerve group. CONCLUSIONS: The new type of tissue engineering scaffold complex of agarose hydrogel and NGF may provide a microenvironment, as well as autograft nerve, to promote nerve regeneration. This technique may benefit patients with nerve injury in the future.