Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Effects of standardized three-stage rehabilitation combined with edaravone therapy on the neurotrophic state and oxidative stress injury in patients with cerebral infarction

Objective: To investigate the effects of standardized three-stage rehabilitation combined with edaravone therapy on the neurotrophic state and oxidative stress injury in patients with cerebral infarction. Methods: A total of 90 patients with acute cerebral infarction who were treated in the hospital between May 2015 and April 2017 were divided into control group (n=45) and observation group (n=45) by random number table. Control group received edaravone therapy, and observation group received standardized three-stage rehabilitation combined with edaravone therapy. The differences in neurotrophic state and oxidative stress injury were compared between the two groups before and after treatment. Results: There was no statistically significant difference in serum levels of neurotrophic indexes and oxidative stress indexes between the two groups before treatment. After treatment, serum neurotrophic indexes BDNF and NGF levels of observation group were higher than those of control group;serum oxidation indexes AOPPs, LHP and MDA levels were lower than those of control group whereas SOD, CAT and T-AOC levels were higher than those of control group. Conclusion:Standardized three-stage rehabilitation combined with edaravone therapy can effectively optimize the neurotrophic state and inhibit the oxidative stress in patients with cerebral infarction.

Optimizing care for gastric cancer with overt bleeding:Is systemic therapy a valid option?

Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.

Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.

Estimating regional coal resource efficiency in China using three-stage DEA and bootstrap DEA models

Based on three-stage data envelopment analysis(DEA) model estimates of resource utilization efficiency of coal,we selected 29 provinces from China's 2012 input-output data and used the bootstrap DEA model to correct the bias.The results show that the mean overall technical efficiency,pure technical efficiency,and scale efficiency was 0.833,0.998,and 0.711 in 2012,respectively.Moreover,the comprehensive technical efficiency score indicates that the scale is invalid.Area utilization efficiencies for the eastern,central,and western regions were 0.917,0.731,and 0.629,respectively.The results prove that there are significant differences in the distribution of coal resources utilization efficiency across regions.

Neoadjuvant therapy for pancreas cancer: Past lessons and future therapies

Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgeryfirst strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.

Investigation on seismic response of a three-stage soil slope supported by anchor frame structure

Based on a typical prototype of a soil slope in engineering practice, a numerical model of a three-stage soil slope supported by the anchor frame structure was established by means of FLAC3D code. The dynamic responses of three-stage soil slope and frame structure were studied by performing a series of bidirectional Wenchuan motions in terms of the failure mode of three-stage structure, the acceleration of soil slope, the displacement of frame structure, and the anchor stress of frame structure. The response accelerations in both horizontal and vertical directions are the most largely amplified at the slope top of each stage subjected to different shaking cases. The platforms among the stages reduce the amplification effect of response acceleration. The residual displacement of frame structure increases significantly as the intensity of shaking case increases. The frame structure at each stage presents a combined displacement mode consisting of a translation and a rotation around the vertex. The anchor stress of frame structure is mainly increased by the first intense pulse of Wenchuan seismic wave, and it is sensitive to the intensity of shaking case. The anchor stress of frame structure at the first stage is the most considerably enlarged by earthquake loading.

When combination therapy isn't working: Emerging therapies for the management of inflammatory bowel disease

Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and immunomodulators, the therapeutic effect is not universal leaving many people searching for options. The development of newer agents has benefited from advances in the understanding of the pathophysiology of the disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. There is increasing evidence of an important role of the innate immune system and the intestinal epithelium, and the therapeutic paradigm is also shifting from immunosuppression to the reinforcement of the intestinal barrier, and modification of the disease process. In this review, we explore the limitation of current therapy as well as mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials.

Production Efficiency of Two-Oriented Agriculture Based on Three-Stage DEA Model

Two-oriented agriculture was a complex organism coupling production,economics,society and ecology.Its development process was affected by various factors such as producers,nature,society,etc.In order to overcome measurement error of traditional data envelopment analysis caused by ignoring random,three-stage DEA model was studied to remove environmental factors and random effects.On the foundation of this model was two-oriented agriculture comprehensive production efficiency of 14 cities were estimated in Hunan Province in 2008,and brown forth corresponding policy proposals to promote agricultural development.

Loco-regional therapies for patients with hepatocellular carcinoma awaiting liver transplantation: Selecting an optimal therapy

Hepatocellular carcinoma(HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation(LT) is considered the most feasible pathway to cure. Resection- even with favorable survival- is associated with a fairly high rate of recurrence, perhaps since most HCCs occur in the setting of cirrhosis. LT offers the advantage of removing not only the cancer but the diseased liver from which the cancer has arisen, and LT outperforms resection for survival with selected patients. Since time waiting for LT is time during which HCC can progress, locoregional therapy(LRT) is widely employed by transplant centers. The purpose of LRT is either to bridge patients to LT by preventing progression and waitlist dropout, or to downstage patients who slightly exceed standard eligibility criteria initially but can fall within it after treatment. Transarterial chemoembolization and radiofrequency ablation have been the most widely utilized LRTs to date, with favorable efficacy and safety as a bridge to LT(and for the former, as a downstaging modality). The list of potentially effective LRTs has expanded in recent years, and includes transarterial chemoembolization with drug-eluting beads, radioembolization and novel forms of extracorporal therapy. Herein we appraise the various LRT modalities for HCC, and their potential roles in specific clinical scenarios in patients awaiting LT.

An Analysis of Operational Efficiency of Agricultural Insurance Agency:Based on Three-Stage DEA Model

From the perspective of agricultural insurance agency,this paper focuses on the study of operational efficiency of agricultural insurance agency,and analyzes the operational efficiency of agricultural insurance agency and its influencing factors,in order to improve the operational efficiency of agricultural insurance agency,better supply agricultural insurance and achieve the policy effect of agricultural insurance.The results of this paper are as follows:( i) Either comprehensive operational efficiency or scale efficiency of Chinese-funded agency is higher than that of foreign-funded agency,but its pure technical efficiency is lower than that of foreign-funded agency,indicating that the managerial decision ability of Chinese-funded agency is weaker than that of foreign-funded agency,and needs to be improved;( ii) The operational efficiency of professional agricultural insurance agency is higher than that of comprehensive agricultural insurance agency,and the agricultural insurance agency is greatly affected by environmental factors;( iii) The operating time of agricultural insurance agency is proportional to its operational efficiency;( iv) The quality of employees is positively correlated with the capital and cost input difference,but negatively correlated with the difference in the number of employees. Therefore,it is necessary to pay attention to the improvement of employees' working efficiency while laying emphasis on employees' quality.

Contribution to the Optimization of the Transient Stability of an Electric Power Transmission Network Using a Universal Power Flow Compensator Controlled by a Three-Stage Inverter

The use of an electrical network as close as possible to its limits can lead to its instability in the event of a high amplitude disturbance. The damping of system oscillations can be achieved by conventional means of voltage and speed regulation but also by FACTS (Flexible AC Transmission Systems) devices, which are increasingly used in power networks. In this work, optimal control coordination between a hybrid power flow controller and a three-level inverter was used to improve the transient stability of a transmission line. The UPFC is a combination of a serial compensator (SSSC) and a parallel compensator (STATCOM) both connected to a DC-LINK DC bus. The SSSC acts as a voltage source for the network and injects a voltage that can be adjusted in phase and amplitude in addition to the network voltage;the STATCOM acts as a current source. The approach used is tested in the Matlab Simulink environment on a single machine network. Optimal controller tuning gives a better transient stability improvement by reducing the transport angle oscillations from 248.17% to 9.85%.

Improving Bandwidth of Three-Stage Electro-Hydraulic Servo Valve Based on Speed-Feedback

In order to improve the dynamic response bandwidth of three-stage electro-hydraulic servo valve,a new method,speed-feedback control is presented in this paper.The construction and principle of three-stage electro-hydraulic servo valve are explained,and the mathematical model of three-stage electro-hydraulic servo valve is built in frequency domain.Experimental and simulation results show that the bandwidth compared with proportional control is improved under speed-feedback control.Moreover,the research results play an important role in developing high performance three-stage electro-hydraulic servo valve.

Numerical Simulation of Enhanced Oil-Water Separation in a Three-Stage Double-Stirring Extraction Tank

Numerical simulation of enhanced fluid flow characteristics in a three-stage double-stirring extraction tank was conducted with the coupling of an Eulerian multiphase flow model and a Morsi-Alexander interphase drag force model. Results show that the addition of a stirring device into the settler can efficiently reduce the volume fraction of out-of-phase impurity in the outlet, and accelerate the settling separation of oil-water mixture. Such addition can also effectively break down the oil-water-wrapped liquid droplets coming from the mixer, inhibit reflux from the outlet, and improve the oil-water separation. The addition of a stirring device induces ignorable power consumption compared with that by the mixer, and can thus facilitate the commercialized promotion of this novel equipment.

A Unique Orogenic System with Three-Stage Rapakivi Granites in the World：Proterozoic,Palaeozoic and Mesozoic Rapakivi Granites in the China Central Orogenic System

Objective Rapakivi granites,characterized by rapakivi texture,Atype granite feature and an anorogenic setting,commonly occur in the Proterozoic of the Northern Hemisphere（Fig.la）.Recently,more and more Phanerozoic rapakivi granite suites have been identified and some even occur in orogenic belts.Significantly,three-stage,Proterozoic.

Advances in radiotherapy and targeted therapies for rectal cancer

The last decade witnessed a significant progress in understanding the biology and immunology of colorectal cancer alongside with the technical innovations in radiotherapy.The stepwise implementation of intensitymodulated and image-guided radiation therapy by means of megavolt computed tomography and helical tomotherapy enabled us to anatomically sculpt dose delivery,reducing treatment related toxicity.In addition,the administration of a simultaneous integrated boost offers excellent local control rates.The novel challenge is the development of treatment strategies for medically inoperable patient and organ preserving approaches.However,distant control remains unsatisfactory and indicates an urgent need for biomarkers that predict the risk of tumor spread.The expected benefit of target?ed therapies that exploit the tumor genome alone is so far hindered by high cost techniques and pharmaceuticals,hence hardly justifying rather modest improvements in patient outcomes.On the other hand,the immune landscape of colorectal cancer is now better clarified with regard to the immunosuppressive network that promotes immune escape.Both N2 neutrophils and myeloid-derived suppressor cells(MDSC)emerge as useful clinical biomarkers of poor prognosis,while the growing list of anti-MDSC agents shows promising ability to boost antitumor T-cell immunity in preclinical settings.Therefore,integration of genetic and immune biomarkers is the next logical step towards effective targeted therapies in the context of personalized cancer treatment.

Combining chemotherapy and targeted therapies in metastatic colorectal cancer

Colorectal cancer remains one of the major causes of cancer death worldwide. During the past years, the development of new effective treatment options has led to a considerable improvement in the outcome of this disease. The advent of agents such as capecitabine, irinotecan, oxaliplatin, cetuximab and bevacizumab has translated into median survival times in the range of 2 years. Intense efforts have focused on identifying novel agents targeting specific growth factor receptors, critical signal transduction pathways or mediators of angiogenesis. In addition, several clinical trials have suggested that some of these molecularly targeted drugs can be safely and effectively used in combination with conventional chemotherapy. In this article we review various treatment options combining cytotoxic and targeted therapies currently available for patients with metastatic colorectal cancer.

A Comparative Study on the Land Use Efficiency of Three Urban Agglomerations-Based on the Three-Stage DEA Model

This paper uses a three-stage DEA model to measure the land use efficiency of the three major urban agglomerations in the Yangtze River Delta,Beijing-Tianjin-Hebei,and the Pearl River Delta from 2007 to 2018.The following conclusions are drawn through research:first,the urban land use efficiency of the three major urban agglomerations in the Yangtze River Delta,Beijing-Tianjin-Hebei,and the Pearl River Delta all showed a downward trend,with the rates of decline being 6.06%,2.86%,and 24.34%respectively.In particular,the Pearl River Delta urban agglomeration had the largest decline.Second,the overall urban land use efficiency of the Beijing-Tianjin-Hebei urban agglomeration is relatively high,and the amount of redundancy is relatively small.The rate of decline is significantly lower than the urban land use efficiency of the two major urban agglomerations in the Yangtze River Delta and the Pearl River Delta.The land use efficiency of the Yangtze River Delta and Pearl River Delta urban agglomerations is in a state of continuous decline.Third,the proportion of cities with the effectiveness of returns to scale of urban land use efficiency in the three major urban agglomerations has decreased by 10.53%,10%,and 33.34%,respectively.The Pearl River Delta has the largest decline.Fourth,the land use efficiency of the Yangtze River Delta urban agglomeration is quite different.The central-peripheral phenomenon is evident for the Beijing-Tianjin-Hebei urban agglomerations and the Pearl River Delta urban agglomerations.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of literature

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.