Geniposide Alleviates Glucocorticoid-Induced Inhibition of Osteogenic Differentiation in MC3T3-E1 Cells by ERK Pathway

Glucocorticoid (GC) therapy is the leading cause of secondary osteoporosis and the therapeutic and preventative drugs for GC-induced osteoporosis are limited. In this study, we investigated the protective effects of geniposide on dexamethasone (DEX)-induced osteogenic inhibition in MC3T3-E1 cells. The results showed that there was no obvious toxicity on MC3T3-E1 cells when geniposide was used at the doses ranging from 1 to 75 μM. In DEX-treated MC3T3-E1 cells, geniposide promoted the alkaline phosphatase (ALP) activity and the mineralization. In addition, geniposide also significantly increased the mRNA and protein expression of osteopontin (OPN), Runt-related transcription factor 2 (Runx2), and Osterix (Osx) in DEX-treated MC3T3-E1 cells. Furthermore, geniposide activated ERK pathway in DEX-treated MC3T3-E1 cells. The ERK activation inhibitor U0126 and glucagon-like peptide-1 (GLP-1) receptor antagonist exendin 9-39 abolished the geniposide-induced activation of ERK and inhibited the protective effect of geniposide. Taken together, our study revealed that geniposide alleviated GC-induced osteogenic suppression in MC3T3-E1 cells. The effect of geniposide was at least partially associated with activating ERK signaling pathway via GLP-1 receptor. Geniposide might be a potential therapeutic agent for GC-induced osteoporosis

The unique immune ecosystems in pediatric brain tumors: integrating single-cell and bulk RNA-sequencing

BackgroundThe significant progress of immune therapy in non-central nervous system tumors has sparked interest in employing the same strategy for adult brain tumors. However, the advancement of immunotherapy in pediatric central nervous system (CNS) tumors is not yet on par. Currently, there is a lack of comprehensive comparative studies investigating the immune ecosystem in pediatric and adult CNS tumors at a high-resolution single-cell level.MethodsIn this study, we comprehensively analyzed over 0.3 million cells from 171 samples, encompassing adult gliomas (IDH wild type and IDH mutation) as well as four major types of pediatric brain tumors (medulloblastoma (MB), ependymoma (EPN), H3K27M-mutation (DIPG), and pediatric IDH-mutation glioma (P-IDH-M)). Our approach involved integrating publicly available and newly generated single-cell datasets. We compared the immune landscapes in different brain tumors, as well as the detailed functional phenotypes of T-cell and myeloid subpopulations. Through single-cell analysis, we identified gene sets associated with major cell types in the tumor microenvironment (gene features from single-cell data, scFes) and compared them with existing gene sets such as GSEA and xCell. The CBTTC and external GEO cohort was used to analyze and validate the immune-stromal-tumor patterns in pediatric brain tumors which might potentially respond to the immunotherapy.ResultsFrom the perspective of single-cell analysis, it was observed that major pediatric brain tumors (MB, EPN, P-IDH-M, DIPG) exhibited lower immune contents compared with adult gliomas. Additionally, these pediatric brain tumors displayed diverse immunophenotypes, particularly in regard to myeloid cells. Notably, the presence of HLA-enriched myeloid cells in MB was found to be independently associated with prognosis. Moreover, the scFes, when compared with commonly used gene features, demonstrated superior performance in independent single-cell datasets across various tumor types. Furthermore, our study revealed the existence of heterogeneous immune ecosystems at the bulk-RNA sequencing level among different brain tumor types. In addition, we identified several immune-stromal-tumor patterns that could potentially exhibit significant responses to conventional immune checkpoint inhibitors.ConclusionThe single-cell technique provides a rational path to deeply understand the unique immune ecosystem of pediatric brain tumors. In spite of the traditional attitudes of “cold” tumor towards pediatric brain tumor, the immune-stroma-tumor patterns identified in this study suggest the feasibility of immune checkpoint inhibitors and pave the way for the upcoming tide of immunotherapy in pediatric brain tumors

Investigation on the Energy-Absorbing Properties of Bionic Spider Web Structure

In recent years, spider webs have received significant attention due to their exceptional mechanical properties, including strength, toughness, elasticity, and robustness. Among these spider webs, the orb web is a prevalent type. An orb web’s main framework consists of radial and spiral threads, with elastic and sticky threads used to capture prey. This paper proposes a bionic orb web model to investigate the energy-absorbing properties of a bionic spider web structure. The model considers structural parameters such as radial line length, radial line cross-sectional diameter, number of spiral lines, spiral spacing, and spiral cross-sectional diameter. These parameters are evaluated to assess the energy absorption capability of the bionic spider web structure. Simulation results reveal that the impact of the radial line length and spiral cross-sectional diameter on the energy absorption of the spider web is more significant compared to the radial line cross-sectional diameter, the number of spiral lines, and spiral spacing. Specifically, within a radial line length range of 60–80 mm, the total absorbed energy of a spider web is inversely proportional to the radial line length of the web. Moreover, the number of spiral lines and spiral spacing of the spider web, when within the range of 6–10 turns and 4–5.5 mm, respectively, are proportional to the total energy absorbed. A regression equation is derived to predict the optimal combination of structural parameters for maximum energy absorption. The optimal parameters are determined as follows: radial line length of 63.48 mm, radial line cross-sectional diameter of 0.46 mm, ten spiral lines, spiral spacing of 5.39 mm, and spiral cross-sectional diameter of 0.48 mm

Traditional Chinese Medicine Yimucao Injection Combined with Western Medicine for Preventing Postpartum Hemorrhage after Cesarean Section: A Systematic Review and Meta-Analysis

Objective. Yimucao injection combined with several contraction uterus drugs is in use for preventing postpartum hemorrhage after cesarean section. The present study is a meta-analysis comparing the efficacy and safety of these drugs. Methods. PubMed, Cochrane Library, Embase, the China National Knowledge Infrastructure (CNKI), the Chinese Biomedical Database (CBM), VIP, and Wanfang database were searched until June 2018. We selected RCTs of Yimucao injection combined with western medicine for preventing postpartum hemorrhage and study quality was assessed using the revised Cochrane risk of bias tool. Forty-eight RCTs are comprised of 7,330 participants. Results. The overall response rate of Yimucao injection combined with western medicine as a class (OR=4.19, 95%CI=2.83, 6.20, P<0.00001) was found to be significantly improved than western medicine alone. Yimucao injection combined with western medicine group could significantly reduce blood loss in intraoperative (SMD= -1.15, 95%CI= -1.43, -0.87, P<0.00001), compared with control group. The treatment group could significantly reduce postpartum blood loss within 2 hours (SMD= -1.73, 95%CI= -2.01, -1.46, P<0.00001) and had a significantly lower blood loss within 24 hours (SMD= -1.92, 95%CI= -2.21, -1.63, P<0.00001) than control group. Additionally, in terms of the safety, Yimucao injection group reduced the risk of adverse events in the course of prevention than the western medicine group. Conclusions. This study demonstrated that Yimucao injection combined with western medicine may be more effective for preventing postpartum hemorrhage after cesarean section. However, high-quality and large multicenter randomized clinical trials will be needed to prove the consequence in the further

Therapeutic Evidence of Human Mesenchymal Stem Cell Transplantation for Cerebral Palsy: A Meta-Analysis of Randomized Controlled Trials

Cerebral palsy (CP) is a kind of movement and posture disorder syndrome in early childhood. In recent years, human mesenchymal stem cell (hMSC) transplantation has become a promising therapeutic strategy for CP. However, clinical evidence is still limited and controversial about clinical efficacy of hMSC therapy for CP. Our aim is to evaluate the efficacy and safety of hMSC transplantation for children with CP using a meta-analysis of randomized controlled trials (RCTs). We conducted a systematic literature search including Embase, PubMed, ClinicalTrials.gov, Cochrane Controlled Trials Register databases, Chinese Clinical Trial Registry, and Web of Science from building database to February 2020. We used Cochrane bias risk assessment for the included studies. The result of pooled analysis showed that hMSC therapy significantly increased gross motor function measure (GMFM) scores (standardized mean difference SMD=1.10, 95%CI=0.66‐1.53, P<0.00001, high-quality evidence) and comprehensive function assessment (CFA) (SMD=1.30, 95%CI=0.71‐1.90, P<0.0001, high-quality evidence) in children with CP, compared with the control group. In the subgroup analysis, the results showed that hMSC therapy significantly increased GMFM scores of 3, 6, and 12 months and CFA of 3, 6, and 12 months. Adverse event (AE) of upper respiratory infection, diarrhea, and constipation was not statistically significant between the two groups. This meta-analysis synthesized the primary outcomes and suggested that hMSC therapy is beneficial, effective, and safe in improving GMFM scores and CFA scores in children with CP. In addition, subgroup analysis showed that hMSC therapy has a lasting positive benefit for CP in 3, 6, and 12 months

Efficacy and Safety of the Injection of the Traditional Chinese Medicine Puerarin for the Treatment of Diabetic Peripheral Neuropathy: A Systematic Review and Meta-Analysis of 53 Randomized Controlled Trials

Objective. The injection of the traditional Chinese patent medicine puerarin has been widely used in the treatment of various diseases such as angina pectoris or ischemic stroke. We aim to evaluate the efficacy and safety of puerarin injection for the treatment of diabetic peripheral neuropathy (DPN). Methods. A systematic literature search was performed in seven medical databases from their inception until June 2017. 53 studies with RCTs, totaling 3284 patients, were included in this meta-analysis. The included studies were assessed by the Cochrane risk of bias and analyzed by Review Manager 5.3 software. Results. The meta-analysis showed that puerarin injection for the treatment of DPN was significantly better compared with the control group in terms of the total effective rate. The result showed that puerarin injection for the treatment of DPN can significantly increase the probability of sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity (MNCV) of the median and peroneal nerves. Conclusions. This meta-analysis demonstrated that puerarin injection may be more effective and safe for the treatment of DPN. However, further and higher quality RCTs are required to prove its efficacy and provide meaningful evidence for clinical treatment due to the poor methodological quality

Autologous Stem Cell Therapy in Critical Limb Ischemia: A Meta-Analysis of Randomized Controlled Trials

Objective. Critical limb ischemia (CLI) is the most dangerous stage of peripheral artery disease (PAD). Many basic researches and clinical treatment had been focused on stem cell transplantation for CLI. This systematic review was performed to review evidence for safety and efficacy of autologous stem cell therapy in CLI. Methods. A systematic literature search was performed in the SinoMed, PubMed, Embase, ClinicalTrials.gov, and Cochrane Controlled Trials Register databases from building database to January 2018. Results. Meta-analysis showed that cell therapy significantly increased the probability of ulcer healing (RR = 1.73, 95% CI = 1.45–2.06), angiogenesis (RR = 5.91, 95% CI = 2.49–14.02), and reduced the amputation rates (RR = 0.59, 95% CI = 0.46–0.76). Ankle-brachial index (ABI) (MD = 0.13, 95% CI = 0.11–0.15), TcO2 (MD = 12.22, 95% CI = 5.03–19.41), and pain-free walking distance (MD = 144.84, 95% CI = 53.03–236.66) were significantly better in the cell therapy group than in the control group (P<0.01). Conclusions. The results of this meta-analysis indicate that autologous stem cell therapy is safe and effective in CLI. However, higher quality and larger RCTs are required for further investigation to support clinical application of stem cell transplantation

A Novel Evaluation Method of Construction Homogeneity for Asphalt Pavement Based on the Characteristic of Component Distribution

To effectively evaluate the construction homogeneity of asphalt pavement, the tomography image of a core sample of asphalt pavement was obtained via industrial computed tomography (CT) equipment. According to the characteristics of CT images, an improved separation algorithm based on annular partition and Nobuyuki Otsu (OTSU) threshold segmentation was proposed. Based on the distribution of aggregates, voids and asphalt mortar, and the area ratio of each part in the CT images inside the pavement, a novel evaluation method for the distribution homogeneity of asphalt pavement components was put forward, and the validity of the evaluation index was also verified. The results show that the aggregates, voids and asphalt mortar in CT images can be effectively segmented by annular partition combined with the OTSU threshold separation algorithm. By superimposing the segmented image on the original image, the segmentation and identification effects of aggregates, voids and asphalt mortar in the CT image are confirmed. Compared with a non-segregated specimen, the average values of the horizontal heterogeneity coefficients of high, medium, light and fine-aggregate-segregated mixtures increased by 72.0%, 48.3%, 34.7% and 16.1%, respectively, where the change range is in accordance with the segregation degrees of several mixtures. The indirect tensile strength of fine-aggregate-, light-, medium- and high-segregated asphalt mixtures decreased by 8.3%, 16.7%, 25.0% and 45.8%, respectively, when compared with the non-segregated asphalt mixture. The index of the vertical heterogeneity coefficient has good correlation with the indirect tensile strength of segregated asphalt mixtures. The construction quality homogeneity of asphalt pavement in different regions can be reliably evaluated by the horizontal heterogeneity coefficient and vertical heterogeneity coefficient

Thermal simulation of microelectrode machining process during block electrical discharge grinding

Electrical discharge machining is widely used in aerospace industries, semiconductor applications, micro-electromechanical systems, and other fields of the machining of micro-holes, micro-shafts, and micro-structures due to non-contact stress during the electrical discharge machining process. In the electrical discharge machining process, the machining precision of electrical discharge machining depends on the dimensional precision of the tool electrode, therefore, the machining process of microelectrode has attracted growing concern. In this study, a thermal model of the microelectrode machining process was proposed to simulate the formation process of microelectrode based on the temperature distribution during block electrical discharge grinding of the microelectrode process. According to the microelectrode machining process, the thermal model considers the main influential factors such as random distribution of discharge points, time-dependent discharge channel radius, Gauss heat source, phase transformation latent heat, etc. Through the thermal simulation analysis, the temperature distribution and the dynamic spark-erosion process of the microelectrode based on random repetitive spark discharges were obtained during block electrical discharge grinding of the microelectrode. Besides, it is found that the maximum temperature value and discharge crater volume of the electrode surface fluctuate and gradually decrease with the increase of discharge times. In addition, the effect of pulse width on the machining process of microelectrode was investigated by numerical simulation and block electrical discharge grinding of microelectrode experiment. The results indicated that the crater volume and the maximum temperature value on the surface of the microelectrode increased with the increase of pulse width. The formation process of microelectrode was considered a significant indicator to determine the machining precision and machining efficiency of the electrical discharge machining process