Background: Current guidelines recommend regional anesthesia versus general as a method of choice for women undergoing cesarean deliveries (CS). However, little is known about the surgical times in the operating room ...Background: Current guidelines recommend regional anesthesia versus general as a method of choice for women undergoing cesarean deliveries (CS). However, little is known about the surgical times in the operating room and a choice of anesthesia for cesarean deliveries. Objective: This study was designed to compare times from the arrival to the OR to the delivery of the fetus between regional and general anesthesia along with maternal and fetal outcomes, for patients undergoing cesarean sections for non-reassuring fetal tracing. Study Design: Records were reviewed for patients who underwent cesarean delivery for non-reassuring fetal heart rate tracing from February 2012 to May 2018. A total of 190 charts were selected. Seven patients who received epidural or spinal anesthesia and then converted to general anesthesia (GA) were excluded. The primary outcomes were: 1) entering the operating room to skin incision (min);2) the time from entering the operating room to delivery of the fetus (min). These times were compared among the patients who underwent epidural, spinal and general anesthesia. The secondary criteria included time from skin incision to delivery of the fetus (min), estimated blood loss (ml), Apgars scores, Arterial/venous cord pH, NICU admissions and fetal complications. ANOVA or Kruskal-Wallis Test was used for the continuous variable and Fisher’s exact test was used for the categorical variable to test the differences between groups. Logistic regression model was used for the binary outcomes after adjusting for age, BMI and number of prior laparotomies. Results: Infants in the GA group were delivered significantly faster when compared to epidural and spinal group separately with a P-value of 0.001. The mean time from arrival to OR to delivery of the newborn in GA group was 12.7 minutes, compared to 27 minutes in epidural group and 32.7 minutes in the spinal group. Time intervals from time in the OR to incision and time from incision to delivery of the fetus were also calculated and were significantly shorter in the GA group when compared to spinal and epidural groups, P Conclusion: The induction of general anesthesia for emergency cesarean section resulted in shorter times to delivery compared to spinal and epidural. General anesthesia was associated with lower, albeit not statistically significant Apgar scores and higher NICU admissions, and had similar cord gases compared to neuraxial anesthesia group.展开更多
This study examined the non-medical factors that influence expectant mothers to opt for caesarean deliveries in Ghana. Data on 395 expectant mothers across the ten regions of Ghana who were located in urban, semi-rura...This study examined the non-medical factors that influence expectant mothers to opt for caesarean deliveries in Ghana. Data on 395 expectant mothers across the ten regions of Ghana who were located in urban, semi-rural and rural areas, and spanned a period of five years (from 2012 to 2016) were obtained from the Ghana Health Service. In fitting the logistic regression model, data on 355 expectant mothers (i.e. 89.9% of the data) was assigned to the analysis sample while 40 (i.e. 10.1%) was assigned to the hold-out sample. The hold-out sample together with other statistical measures of overall model fit, pseudo R2 measures and classification accuracy were used to validate the results obtained from the analysis sample. Significance was tested at p = 0.05. Determinants including, educational level of expectant mother, parity of expectant mother, baby’s birth weight, previous caesarean delivery, location of expectant mother, age of expectant mother and, period within the year of childbirth had a significant effect on caesarean delivery. The study recommended that health practitioners should be able to foretell expectant mothers who are likely to undergo caesarean delivery in order for them to prepare financially and psychologically to avoid further complications. Due to the significant positive attitude of women towards caesarean delivery rather than normal delivery, it is necessary to inform them about the advantages of normal delivery and the health hazards associated with caesarean delivery to the mother and child.展开更多
The essential nutrition actions explain nutrition through life cycle approach addressing women’s nutrition during pregnancy and lactation, optimal infant and young children feeding, nutritional care for sick children...The essential nutrition actions explain nutrition through life cycle approach addressing women’s nutrition during pregnancy and lactation, optimal infant and young children feeding, nutritional care for sick children and control of anemia, iodine and vitamin A deficiencies. Essential nutrition action has been implemented and resulted in positive outcome in less developed countries. However, the status of practice and associated factors were not studied in Ethiopia. Thus, institution-based cross-sectional study was conducted to assess the practice of essential nutrition actions in healthcare deliveries of Shebedino District, South Ethiopia. Quantitative data were collected though face-to-face interview with health workers and triangulated with data obtained through in-depth interview with health managers in the district and non-participatory observation of client-provider interaction in health facilities. Data were analyzed using SPSS16.0 software. Descriptive and logistic regression analyses were undertaken. The study revealed that 61 (56.0%) health workers practiced essential nutrition actions. Seventy one (65.1%) health workers were trained on essential nutrition actions. The practice of essential nutrition actions was associated with career structure of the health workers (AOR = 6.79, 95%CI: 2.31, 19.98), essential nutrition actions knowledge of health workers (AOR = 6.87, 95%CI: 2.11, 21.51) and availability of monthly nutrition related report form (AOR = 4.95, 95%CI: 1.46, 16.81). The practice of essential nutrition actions was low. The factors affecting the practice were inadequate training and knowledge of essential nutrition actions, career structure of the health workers and availability of monthly report form. Training should be provided for health workers on essential nutrition actions;moreover, essential nutrition actions indicators should be included in monthly report forms of the health institutions.展开更多
In this study,we investigate a forest-based solution representation for split delivery vehicle routing problems(SDVRPs),which have several practical applications and are among the most difficult vehicle routing proble...In this study,we investigate a forest-based solution representation for split delivery vehicle routing problems(SDVRPs),which have several practical applications and are among the most difficult vehicle routing problems.The new solution representation fully reflects the nature of split delivery,and can help reduce the search space when used in heuristic algorithms.Based on the forest structure,we devise three neighborhood search operators.To highlight the effectiveness of this solution representation,we integrate these operators into a standard tabu search framework.We conduct extensive experiments on three main SDVRPs addressed in the literature:The basic SDVRP,the multidepot SDVRP,and the SDVRP with time windows.The experimental results show that the new forest-based solution representation is particularly effective in designing and implementing neighborhood operators,and that our new approach outperforms state-of-the-art algorithms on standard datasets.展开更多
The vehicle routing problem(VRP) is a well-known combinatorial optimization issue in transportation and logistics network systems. There exist several limitations associated with the traditional VRP. Releasing the res...The vehicle routing problem(VRP) is a well-known combinatorial optimization issue in transportation and logistics network systems. There exist several limitations associated with the traditional VRP. Releasing the restricted conditions of traditional VRP has become a research focus in the past few decades. The vehicle routing problem with split deliveries and pickups(VRPSPDP) is particularly proposed to release the constraints on the visiting times per customer and vehicle capacity, that is, to allow the deliveries and pickups for each customer to be simultaneously split more than once. Few studies have focused on the VRPSPDP problem. In this paper we propose a two-stage heuristic method integrating the initial heuristic algorithm and hybrid heuristic algorithm to study the VRPSPDP problem. To validate the proposed algorithm, Solomon benchmark datasets and extended Solomon benchmark datasets were modified to compare with three other popular algorithms. A total of 18 datasets were used to evaluate the effectiveness of the proposed method. The computational results indicated that the proposed algorithm is superior to these three algorithms for VRPSPDP in terms of total travel cost and average loading rate.展开更多
The low efficiency and high cost of fresh agricultural product terminal distribution directly restrict the operation of the entire supply network.To reduce costs and optimize the distribution network,we construct a mi...The low efficiency and high cost of fresh agricultural product terminal distribution directly restrict the operation of the entire supply network.To reduce costs and optimize the distribution network,we construct a mixed integer programmingmodel that comprehensively considers tominimize fixed,transportation,fresh-keeping,time,carbon emissions,and performance incentive costs.We analyzed the performance of traditional rider distribution and robot distribution modes in detail.In addition,the uncertainty of the actual market demand poses a huge threat to the stability of the terminal distribution network.In order to resist uncertain interference,we further extend the model to a robust counterpart form.The results of the simulation show that the instability of random parameters will lead to an increase in the cost.Compared with the traditional rider distribution mode,the robot distribution mode can save 12.7%on logistics costs,and the distribution efficiency is higher.Our research can provide support for the design of planning schemes for transportation enterprise managers.展开更多
The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alz...The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.展开更多
Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and...Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular level.However,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date.Here,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular nanomedicines.Poly(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in macrophages.By adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles.Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over time.Based on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation timelines.More importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in cells.In summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.展开更多
BACKGROUND:Postpartum posttraumatic stress disorder(PTSD)can occur in women who give birth after emergency admission.The identification of risk factors for this condition is crucial for developing effective preventive...BACKGROUND:Postpartum posttraumatic stress disorder(PTSD)can occur in women who give birth after emergency admission.The identification of risk factors for this condition is crucial for developing effective preventive measures.This retrospective study aimed to explore the incidence and risk factors for postpartum PTSD in women who give birth after emergency admission.METHODS:Medical records of women who gave birth after emergency admission were collected between March 2021 and April 2023.The patients’general conditions and perinatal clinical indicators were recorded.The puerperae were divided into PTSD group and control group based on symptom occurrence at six weeks postpartum.Multivariate logistic regression analysis was performed to identify risk factors.RESULTS:A total of 276 puerperae were included,with a PTSD incidence of 20.3% at six weeks postpartum.Multivariate logistic regression analysis identified emergency cesarean section(odds ratio[OR]=2.102;95%confidence interval[CI]:1.114-3.966,P=0.022),admission to the emergency department after midnight(12:00 AM)(OR=2.245;95%CI:1.170-4.305,P<0.001),and cervical dilation(OR=3.203;95%CI:1.670–6.141,P=0.039)as independent risk factors for postpartum PTSD.Analgesia pump use(OR=0.500;95%CI:0.259–0.966,P=0.015)was found to be a protective factor against postpartum PTSD.CONCLUSION:Emergency cesarean section,admission to the emergency department after midnight,and cervical dilation were identified as independent risk factors for postpartum PTSD,while analgesic pump use was a protective factor.These findings provide insights for developing more effective preventive measures for women who give birth after emergency admission.展开更多
Cooperative utilization of multidimensional resources including cache, power and spectrum in satellite-terrestrial integrated networks(STINs) can provide a feasible approach for massive streaming media content deliver...Cooperative utilization of multidimensional resources including cache, power and spectrum in satellite-terrestrial integrated networks(STINs) can provide a feasible approach for massive streaming media content delivery over the seamless global coverage area. However, the on-board supportable resources of a single satellite are extremely limited and lack of interaction with others. In this paper, we design a network model with two-layered cache deployment, i.e., satellite layer and ground base station layer, and two types of sharing links, i.e., terrestrial-satellite sharing(TSS) links and inter-satellite sharing(ISS) links, to enhance the capability of cooperative delivery over STINs. Thus, we use rateless codes for the content divided-packet transmission, and derive the total energy efficiency(EE) in the whole transmission procedure, which is defined as the ratio of traffic offloading and energy consumption. We formulate two optimization problems about maximizing EE in different sharing scenarios(only TSS and TSS-ISS),and propose two optimized algorithms to obtain the optimal content placement matrixes, respectively.Simulation results demonstrate that, enabling sharing links with optimized cache placement have more than 2 times improvement of EE performance than other traditional placement schemes. Particularly, TSS-ISS schemes have the higher EE performance than only TSS schemes under the conditions of enough number of satellites and smaller inter-satellite distances.展开更多
Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescen...Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.展开更多
Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none o...Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.展开更多
In this paper,a dynamic modeling method of motor driven electromechanical system is presented,and the uncertainty quantification of mechanism motion is investigated based on this method.The main contribution is to pro...In this paper,a dynamic modeling method of motor driven electromechanical system is presented,and the uncertainty quantification of mechanism motion is investigated based on this method.The main contribution is to propose a novel mechanism-motor coupling dynamic modeling method,in which the relationship between mechanism motion and motor rotation is established according to the geometric coordination of the system.The advantages of this include establishing intuitive coupling between the mechanism and motor,facilitating the discussion for the influence of both mechanical and electrical parameters on the mechanism,and enabling dynamic simulation with controller to take the randomness of the electric load into account.Dynamic simulation considering feedback control of ammunition delivery system is carried out,and the feasibility of the model is verified experimentally.Based on probability density evolution theory,we comprehensively discuss the effects of system parameters on mechanism motion from the perspective of uncertainty quantization.Our work can not only provide guidance for engineering design of ammunition delivery mechanism,but also provide theoretical support for modeling and uncertainty quantification research of mechatronics system.展开更多
The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) ...The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) and sudden sensorineural hearing loss (SSHL).Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin.Dexamethasone was constantly released for at least 16 d at a stable level after 7d in protocol 1 (low-dose),while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2(high-dose).There were significant differences among the time points in Protocol 2 (p<0.01,ANOVA),and the exponential model with the formula y=15.299*e~(-0.483*t) fits the association.The estimated concentration of dexamethasone released on 7 d in protocol 2 was slightly lower than that observed in protocol 1.The fibrin sealant is capable of constantly releasing dexamethasone with adjustable dynamics.Targeted and minimally invasive administration of the material can be achieved in the clinic by sequential injections of the fluids using a soft-tipped catheter.展开更多
The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of...The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of non-involved tissues to cytotoxic agents.Mesenchymal stromal cells(MSC)represent a group of undifferentiated multipotent cells presenting wide self-renewal features and the capacity to differentiate into an assortment of mesenchymal family cells.During the last year,they have been proposed as natural carriers for the selective release of antitumor drugs to malignant cll,s thus optimizing cytotoxic action on cancer cll,while significantly reducing adverse side efect on healthy cells.MSC chemotherapeutic drug loading and delivery is an encouraging new area of cell therapy for several tumors,especially for those with unsatisfactory prognosis and limited treatment options available.Although some experim ental models have been sucesfuly developed,phase I dinical studies are needed to confirm this potential application of cell therapy,in particular in the case of primary and secondary lung cancers.展开更多
Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone ...Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.展开更多
The study focuses on the development of biocompatible and stable FA-functionalized nanocrystalline cellulose(NCC)as a potential drug delivery system for targeting folate receptor-positive cancer cells.The FA-functiona...The study focuses on the development of biocompatible and stable FA-functionalized nanocrystalline cellulose(NCC)as a potential drug delivery system for targeting folate receptor-positive cancer cells.The FA-functionalized NCCs were synthesized through a series of chemical reactions,resulting in nanoparticles with favorable properties for biomedical applications.The microstructural analysis revealed that the functionalized NCCs maintained their rod-shaped morphology and displayed hydrodynamic diameters suitable for evading the mononuclear phagocytic system while being large enough to target tumor tissues.Importantly,these nanoparticles possessed a negative surface charge,enhancing their stability and repelling potential aggregation.The binding specificity of FA-functionalized NCCs to folate receptor-positive cancer cells was demonstrated through various assays.The free folic acid inhibition assay showed approximately 30%decrease in the binding of functionalized NCCs in the presence of just 5 mM free FA,confirming their selectivity for folate receptor-positive cells.Confocal microscopy further validated this specificity,as only cancer cells displayed significant binding of functionalized NCCs.Crucially,biocompatibility tests revealed that both NCCs and FA-functionalized NCCs had minimal effects on red blood cells,and they did not induce erythrocyte aggregation.Furthermore,cell viability assays demonstrated functionalized NCCs have selective cytotoxicity against colorectal cancer cells HT-29 and SW-620(68%–88%cell viability)while sparing noncancerous colon cells CCD-18Co(81%–97%cell viability).In summary,FA-functionalized NCCs exhibit promising characteristics for targeted drug delivery in cancer therapy.Their biocompatibility,stability,and selective cytotoxicity make them an attractive option for delivering therapeutic agents to folate receptor-positive cancer cells,potentially improving the effectiveness of cancer treatments while minimizing harm to healthy tissues.展开更多
Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk...Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk1/CTX-Lip).Methods:Physical and chemical properties of Rk1/CTX-Lip were investigated.We evaluated the biological functions of Rk1/CTXLip,both in vitro and in vivo.A subcutaneous prostate cancer(RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors.Simultaneously,a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip.Finally,biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated.Results:We successfully prepared Rk1/CTX-Lip,achieving high CTX encapsulation efficiency(97.24±0.75)%and physical stability.Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis,effective tumor tissue targeting,and a significant reduction(>50%)in average tumor volume compared with Chol/CTX-Lip.Moreover,it relieved the concurrent infection burden and effectively regulated immune organs and cells,demonstrating superior biocompatibility.Conclusion:Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.展开更多
Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a p...Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.展开更多
BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL system...BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical practice.In this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic’s 670G HCL in real-world clinical practice.AIM To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D.METHODS We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1C:7.6%±0.8%)who were treated with HCL at Joslin Clinic from 2017 to 2019.We measured A1C and percent of glucose time-in-range(%TIR)at baseline and 12 months.We measured percent time in auto mode(%TiAM)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management.RESULTS At 12 mo,A1C decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAM was only 64.3%±32.8%and was not associated with A1C,%TIR or PROs.PROs,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(P<0.001).Hypoglycemia fear survey/worry scale decreased significantly by 24.9%(P<0.000);Problem Areas In Diabetes reduced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes.WHO-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HCL system.Finally,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration of sleep from baseline to 12 mo.CONCLUSION The use of HCL in real-world clinical practice for one year was associated with significant improvements in A1C,%TIR,physical functioning,hypoglycemia fear,emotional distress,and emotional burden related to diabetes management.However,these changes were not associated with time in auto mode.展开更多
文摘Background: Current guidelines recommend regional anesthesia versus general as a method of choice for women undergoing cesarean deliveries (CS). However, little is known about the surgical times in the operating room and a choice of anesthesia for cesarean deliveries. Objective: This study was designed to compare times from the arrival to the OR to the delivery of the fetus between regional and general anesthesia along with maternal and fetal outcomes, for patients undergoing cesarean sections for non-reassuring fetal tracing. Study Design: Records were reviewed for patients who underwent cesarean delivery for non-reassuring fetal heart rate tracing from February 2012 to May 2018. A total of 190 charts were selected. Seven patients who received epidural or spinal anesthesia and then converted to general anesthesia (GA) were excluded. The primary outcomes were: 1) entering the operating room to skin incision (min);2) the time from entering the operating room to delivery of the fetus (min). These times were compared among the patients who underwent epidural, spinal and general anesthesia. The secondary criteria included time from skin incision to delivery of the fetus (min), estimated blood loss (ml), Apgars scores, Arterial/venous cord pH, NICU admissions and fetal complications. ANOVA or Kruskal-Wallis Test was used for the continuous variable and Fisher’s exact test was used for the categorical variable to test the differences between groups. Logistic regression model was used for the binary outcomes after adjusting for age, BMI and number of prior laparotomies. Results: Infants in the GA group were delivered significantly faster when compared to epidural and spinal group separately with a P-value of 0.001. The mean time from arrival to OR to delivery of the newborn in GA group was 12.7 minutes, compared to 27 minutes in epidural group and 32.7 minutes in the spinal group. Time intervals from time in the OR to incision and time from incision to delivery of the fetus were also calculated and were significantly shorter in the GA group when compared to spinal and epidural groups, P Conclusion: The induction of general anesthesia for emergency cesarean section resulted in shorter times to delivery compared to spinal and epidural. General anesthesia was associated with lower, albeit not statistically significant Apgar scores and higher NICU admissions, and had similar cord gases compared to neuraxial anesthesia group.
文摘This study examined the non-medical factors that influence expectant mothers to opt for caesarean deliveries in Ghana. Data on 395 expectant mothers across the ten regions of Ghana who were located in urban, semi-rural and rural areas, and spanned a period of five years (from 2012 to 2016) were obtained from the Ghana Health Service. In fitting the logistic regression model, data on 355 expectant mothers (i.e. 89.9% of the data) was assigned to the analysis sample while 40 (i.e. 10.1%) was assigned to the hold-out sample. The hold-out sample together with other statistical measures of overall model fit, pseudo R2 measures and classification accuracy were used to validate the results obtained from the analysis sample. Significance was tested at p = 0.05. Determinants including, educational level of expectant mother, parity of expectant mother, baby’s birth weight, previous caesarean delivery, location of expectant mother, age of expectant mother and, period within the year of childbirth had a significant effect on caesarean delivery. The study recommended that health practitioners should be able to foretell expectant mothers who are likely to undergo caesarean delivery in order for them to prepare financially and psychologically to avoid further complications. Due to the significant positive attitude of women towards caesarean delivery rather than normal delivery, it is necessary to inform them about the advantages of normal delivery and the health hazards associated with caesarean delivery to the mother and child.
文摘The essential nutrition actions explain nutrition through life cycle approach addressing women’s nutrition during pregnancy and lactation, optimal infant and young children feeding, nutritional care for sick children and control of anemia, iodine and vitamin A deficiencies. Essential nutrition action has been implemented and resulted in positive outcome in less developed countries. However, the status of practice and associated factors were not studied in Ethiopia. Thus, institution-based cross-sectional study was conducted to assess the practice of essential nutrition actions in healthcare deliveries of Shebedino District, South Ethiopia. Quantitative data were collected though face-to-face interview with health workers and triangulated with data obtained through in-depth interview with health managers in the district and non-participatory observation of client-provider interaction in health facilities. Data were analyzed using SPSS16.0 software. Descriptive and logistic regression analyses were undertaken. The study revealed that 61 (56.0%) health workers practiced essential nutrition actions. Seventy one (65.1%) health workers were trained on essential nutrition actions. The practice of essential nutrition actions was associated with career structure of the health workers (AOR = 6.79, 95%CI: 2.31, 19.98), essential nutrition actions knowledge of health workers (AOR = 6.87, 95%CI: 2.11, 21.51) and availability of monthly nutrition related report form (AOR = 4.95, 95%CI: 1.46, 16.81). The practice of essential nutrition actions was low. The factors affecting the practice were inadequate training and knowledge of essential nutrition actions, career structure of the health workers and availability of monthly report form. Training should be provided for health workers on essential nutrition actions;moreover, essential nutrition actions indicators should be included in monthly report forms of the health institutions.
文摘In this study,we investigate a forest-based solution representation for split delivery vehicle routing problems(SDVRPs),which have several practical applications and are among the most difficult vehicle routing problems.The new solution representation fully reflects the nature of split delivery,and can help reduce the search space when used in heuristic algorithms.Based on the forest structure,we devise three neighborhood search operators.To highlight the effectiveness of this solution representation,we integrate these operators into a standard tabu search framework.We conduct extensive experiments on three main SDVRPs addressed in the literature:The basic SDVRP,the multidepot SDVRP,and the SDVRP with time windows.The experimental results show that the new forest-based solution representation is particularly effective in designing and implementing neighborhood operators,and that our new approach outperforms state-of-the-art algorithms on standard datasets.
基金Project supported by the National Natural Science Foundation of China(No.51138003)the National Social Science Foundation of Chongqing of China(No.2013YBJJ035)
文摘The vehicle routing problem(VRP) is a well-known combinatorial optimization issue in transportation and logistics network systems. There exist several limitations associated with the traditional VRP. Releasing the restricted conditions of traditional VRP has become a research focus in the past few decades. The vehicle routing problem with split deliveries and pickups(VRPSPDP) is particularly proposed to release the constraints on the visiting times per customer and vehicle capacity, that is, to allow the deliveries and pickups for each customer to be simultaneously split more than once. Few studies have focused on the VRPSPDP problem. In this paper we propose a two-stage heuristic method integrating the initial heuristic algorithm and hybrid heuristic algorithm to study the VRPSPDP problem. To validate the proposed algorithm, Solomon benchmark datasets and extended Solomon benchmark datasets were modified to compare with three other popular algorithms. A total of 18 datasets were used to evaluate the effectiveness of the proposed method. The computational results indicated that the proposed algorithm is superior to these three algorithms for VRPSPDP in terms of total travel cost and average loading rate.
文摘The low efficiency and high cost of fresh agricultural product terminal distribution directly restrict the operation of the entire supply network.To reduce costs and optimize the distribution network,we construct a mixed integer programmingmodel that comprehensively considers tominimize fixed,transportation,fresh-keeping,time,carbon emissions,and performance incentive costs.We analyzed the performance of traditional rider distribution and robot distribution modes in detail.In addition,the uncertainty of the actual market demand poses a huge threat to the stability of the terminal distribution network.In order to resist uncertain interference,we further extend the model to a robust counterpart form.The results of the simulation show that the instability of random parameters will lead to an increase in the cost.Compared with the traditional rider distribution mode,the robot distribution mode can save 12.7%on logistics costs,and the distribution efficiency is higher.Our research can provide support for the design of planning schemes for transportation enterprise managers.
基金supported by the National Natural Science Foundation of China,Nos.82072051 and 81771964(both to JG)the Natural Science Foundation of Shanghai Municipal Science and Technology Commission,No.22ZR147750(to YY)+2 种基金Science and Technology Support Projects in Biomedicine Field of Shanghai Science and Technology Commission,No.19441907500(to YY)Innovative Clinical Research Project of Changzheng Hospital,No.2020 YLCYJ-Y02(to YY)Characteristic Medical Service Project for the Army of Changzheng Hospital,No.2020 CZWJFW12(to YY)。
文摘The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.
基金supported by Natural Science Foundation of Beijing Municipality(L212013)National Key Research and Development Program of China(No.2022YFA1206104)+2 种基金AI+Health Collaborative Innovation Cultivation Project(Z211100003521002)National Natural Science Foundation of China(81971718,82073786,81872809,U20A20412,81821004)Beijing Natural Science Foundation(7222020).
文摘Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular level.However,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date.Here,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular nanomedicines.Poly(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in macrophages.By adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles.Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over time.Based on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation timelines.More importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in cells.In summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.
基金Science and Technology Development Plan Project of Suzhou(SKJYD2021035)Science and Technology Development Plan Project of Suzhou(SKJYD2022078)The Key Project Research Fund of the Second Affiliated Hospital of Wannan Medical College(YK2023Z04)。
文摘BACKGROUND:Postpartum posttraumatic stress disorder(PTSD)can occur in women who give birth after emergency admission.The identification of risk factors for this condition is crucial for developing effective preventive measures.This retrospective study aimed to explore the incidence and risk factors for postpartum PTSD in women who give birth after emergency admission.METHODS:Medical records of women who gave birth after emergency admission were collected between March 2021 and April 2023.The patients’general conditions and perinatal clinical indicators were recorded.The puerperae were divided into PTSD group and control group based on symptom occurrence at six weeks postpartum.Multivariate logistic regression analysis was performed to identify risk factors.RESULTS:A total of 276 puerperae were included,with a PTSD incidence of 20.3% at six weeks postpartum.Multivariate logistic regression analysis identified emergency cesarean section(odds ratio[OR]=2.102;95%confidence interval[CI]:1.114-3.966,P=0.022),admission to the emergency department after midnight(12:00 AM)(OR=2.245;95%CI:1.170-4.305,P<0.001),and cervical dilation(OR=3.203;95%CI:1.670–6.141,P=0.039)as independent risk factors for postpartum PTSD.Analgesia pump use(OR=0.500;95%CI:0.259–0.966,P=0.015)was found to be a protective factor against postpartum PTSD.CONCLUSION:Emergency cesarean section,admission to the emergency department after midnight,and cervical dilation were identified as independent risk factors for postpartum PTSD,while analgesic pump use was a protective factor.These findings provide insights for developing more effective preventive measures for women who give birth after emergency admission.
基金supported by National Natural Sciences Foundation of China(No.62271165,62027802,61831008)the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515030297,2021A1515011572)Shenzhen Science and Technology Program ZDSYS20210623091808025,Stable Support Plan Program GXWD20231129102638002.
文摘Cooperative utilization of multidimensional resources including cache, power and spectrum in satellite-terrestrial integrated networks(STINs) can provide a feasible approach for massive streaming media content delivery over the seamless global coverage area. However, the on-board supportable resources of a single satellite are extremely limited and lack of interaction with others. In this paper, we design a network model with two-layered cache deployment, i.e., satellite layer and ground base station layer, and two types of sharing links, i.e., terrestrial-satellite sharing(TSS) links and inter-satellite sharing(ISS) links, to enhance the capability of cooperative delivery over STINs. Thus, we use rateless codes for the content divided-packet transmission, and derive the total energy efficiency(EE) in the whole transmission procedure, which is defined as the ratio of traffic offloading and energy consumption. We formulate two optimization problems about maximizing EE in different sharing scenarios(only TSS and TSS-ISS),and propose two optimized algorithms to obtain the optimal content placement matrixes, respectively.Simulation results demonstrate that, enabling sharing links with optimized cache placement have more than 2 times improvement of EE performance than other traditional placement schemes. Particularly, TSS-ISS schemes have the higher EE performance than only TSS schemes under the conditions of enough number of satellites and smaller inter-satellite distances.
基金supported by Dalian Youth Science and Technology Star Project(2020RQ121)the National Science Fund for Distinguished Young Scholars of China(31925031)+1 种基金Doctoral Scientific Research Foundation of Liaoning Province(2020-BS-211)Liaoning Province Education Administration(J2020101)。
文摘Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.
基金supported by the 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant,No.2020LKSFG02C(to Qiang Fang and SG)the National Natural Science Foundation of China,No.82201511(to SG)+1 种基金the Guangdong Basic and Applied Basic Research Foundation,Nos.2021A1515110873(to SG),2022A1515110139(to TW)the Medical Scientific Research Foundation of Guangdong Province,No.A2022077(to SG)。
文摘Spinal cord injury is a severe insult to the central nervous system that causes persisting neurological deficits.The currently available treatments involve surgical,medical,and rehabilitative strategies.However,none of these techniques can markedly reverse neurological deficits.Recently,extracellular vesicles from various cell sources have been applied to different models of spinal cord injury,thereby generating new cell-free therapies for the treatment of spinal cord injury.However,the use of extracellular vesicles alone is still associated with some notable shortcomings,such as their uncertainty in targeting damaged spinal cord tissues and inability to provide structural support to damaged axons.Therefore,this paper reviews the latest combined strategies for the use of extracellular vesicle-based technology for spinal cord injury,including the combination of extracellular vesicles with nanoparticles,exogenous drugs and/or biological scaffold materials,which facilitate the targeting ability of extracellular vesicles and the combinatorial effects with extracellular vesicles.We also highlight issues relating to the clinical transformation of these extracellular vesicle-based combination strategies for the treatment of spinal cord injury.
基金supported by the National Natural Science Foundation of China(Grant Nos.11472137 and U2141246)。
文摘In this paper,a dynamic modeling method of motor driven electromechanical system is presented,and the uncertainty quantification of mechanism motion is investigated based on this method.The main contribution is to propose a novel mechanism-motor coupling dynamic modeling method,in which the relationship between mechanism motion and motor rotation is established according to the geometric coordination of the system.The advantages of this include establishing intuitive coupling between the mechanism and motor,facilitating the discussion for the influence of both mechanical and electrical parameters on the mechanism,and enabling dynamic simulation with controller to take the randomness of the electric load into account.Dynamic simulation considering feedback control of ammunition delivery system is carried out,and the feasibility of the model is verified experimentally.Based on probability density evolution theory,we comprehensively discuss the effects of system parameters on mechanism motion from the perspective of uncertainty quantization.Our work can not only provide guidance for engineering design of ammunition delivery mechanism,but also provide theoretical support for modeling and uncertainty quantification research of mechatronics system.
基金supported by the National Natural Science Foundation of China(81771006)。
文摘The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) and sudden sensorineural hearing loss (SSHL).Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin.Dexamethasone was constantly released for at least 16 d at a stable level after 7d in protocol 1 (low-dose),while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2(high-dose).There were significant differences among the time points in Protocol 2 (p<0.01,ANOVA),and the exponential model with the formula y=15.299*e~(-0.483*t) fits the association.The estimated concentration of dexamethasone released on 7 d in protocol 2 was slightly lower than that observed in protocol 1.The fibrin sealant is capable of constantly releasing dexamethasone with adjustable dynamics.Targeted and minimally invasive administration of the material can be achieved in the clinic by sequential injections of the fluids using a soft-tipped catheter.
文摘The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues,thus incrementing drug effects and,at the same time,reducing the damage of non-involved tissues to cytotoxic agents.Mesenchymal stromal cells(MSC)represent a group of undifferentiated multipotent cells presenting wide self-renewal features and the capacity to differentiate into an assortment of mesenchymal family cells.During the last year,they have been proposed as natural carriers for the selective release of antitumor drugs to malignant cll,s thus optimizing cytotoxic action on cancer cll,while significantly reducing adverse side efect on healthy cells.MSC chemotherapeutic drug loading and delivery is an encouraging new area of cell therapy for several tumors,especially for those with unsatisfactory prognosis and limited treatment options available.Although some experim ental models have been sucesfuly developed,phase I dinical studies are needed to confirm this potential application of cell therapy,in particular in the case of primary and secondary lung cancers.
基金supported by the National Natural Science Foundation of China(#81872220 and#81703437)Xinjiang Uygur Autonomous Region Science and Technology Support Project(#2020E0290)+4 种基金Basic Public Welfare Research Project of Zhejiang Province(#LGF18H160034,LGC21B050011 and#LGF20H300012),Science and Technology Bureau of Jiaxing(2020AY10021)Key Research and Development and Transformation project of Qinghai Province(2021-SF-C20)Dutch Cancer Foundation(KWF project#10666)a Zhejiang Provincial Foreign Expert Program Grant,Zhejiang Provincial Key Natural Science Foundation of China(#Z20H160031)and Jiaxing Key Laboratory of Oncological Photodynamic Therapy and Targeted Drug Research,and“Innovative Jiaxing·Excellent Talent Support Program”-Top Talents in Technological Innovation.
文摘Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.
基金funded by Ministry of Higher Education(MOHE),Malaysia-Prototype Development Research Grant Scheme,Grant Number PRGS/1/2020/STG05/UM/02/1.
文摘The study focuses on the development of biocompatible and stable FA-functionalized nanocrystalline cellulose(NCC)as a potential drug delivery system for targeting folate receptor-positive cancer cells.The FA-functionalized NCCs were synthesized through a series of chemical reactions,resulting in nanoparticles with favorable properties for biomedical applications.The microstructural analysis revealed that the functionalized NCCs maintained their rod-shaped morphology and displayed hydrodynamic diameters suitable for evading the mononuclear phagocytic system while being large enough to target tumor tissues.Importantly,these nanoparticles possessed a negative surface charge,enhancing their stability and repelling potential aggregation.The binding specificity of FA-functionalized NCCs to folate receptor-positive cancer cells was demonstrated through various assays.The free folic acid inhibition assay showed approximately 30%decrease in the binding of functionalized NCCs in the presence of just 5 mM free FA,confirming their selectivity for folate receptor-positive cells.Confocal microscopy further validated this specificity,as only cancer cells displayed significant binding of functionalized NCCs.Crucially,biocompatibility tests revealed that both NCCs and FA-functionalized NCCs had minimal effects on red blood cells,and they did not induce erythrocyte aggregation.Furthermore,cell viability assays demonstrated functionalized NCCs have selective cytotoxicity against colorectal cancer cells HT-29 and SW-620(68%–88%cell viability)while sparing noncancerous colon cells CCD-18Co(81%–97%cell viability).In summary,FA-functionalized NCCs exhibit promising characteristics for targeted drug delivery in cancer therapy.Their biocompatibility,stability,and selective cytotoxicity make them an attractive option for delivering therapeutic agents to folate receptor-positive cancer cells,potentially improving the effectiveness of cancer treatments while minimizing harm to healthy tissues.
基金supported by the National Natural Science Foundation of China(82373808)Chongqing Natural Science Foundation(cstc2021jcyj-bshX0125)+1 种基金Fundamental Research Funds for the Central Universities(SWURC2020001)the project for Chongqing University Innovation Research Group,Chongqing Education Committee(CXQT20006).
文摘Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk1/CTX-Lip).Methods:Physical and chemical properties of Rk1/CTX-Lip were investigated.We evaluated the biological functions of Rk1/CTXLip,both in vitro and in vivo.A subcutaneous prostate cancer(RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors.Simultaneously,a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip.Finally,biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated.Results:We successfully prepared Rk1/CTX-Lip,achieving high CTX encapsulation efficiency(97.24±0.75)%and physical stability.Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis,effective tumor tissue targeting,and a significant reduction(>50%)in average tumor volume compared with Chol/CTX-Lip.Moreover,it relieved the concurrent infection burden and effectively regulated immune organs and cells,demonstrating superior biocompatibility.Conclusion:Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.
基金supported by the National Key Research and Development Program of China,Nos.2017YFE0122900(to BH),2019YFA0110800(to WL),2019YFA0903802(to YW),2021YFA1101604(to LW),2018YFA0108502(to LF),and 2020YFA0804003(to JW)the National Natural Science Foundation of China,Nos.31621004(to WL,BH)and 31970821(to YW)+1 种基金CAS Project for Young Scientists in Basic Research,No.YSBR-041(to YW)Joint Funds of the National Natural Science Foundation of China,No.U21A20396(to BH)。
文摘Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.
文摘BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical practice.In this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic’s 670G HCL in real-world clinical practice.AIM To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D.METHODS We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1C:7.6%±0.8%)who were treated with HCL at Joslin Clinic from 2017 to 2019.We measured A1C and percent of glucose time-in-range(%TIR)at baseline and 12 months.We measured percent time in auto mode(%TiAM)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management.RESULTS At 12 mo,A1C decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAM was only 64.3%±32.8%and was not associated with A1C,%TIR or PROs.PROs,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(P<0.001).Hypoglycemia fear survey/worry scale decreased significantly by 24.9%(P<0.000);Problem Areas In Diabetes reduced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes.WHO-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HCL system.Finally,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration of sleep from baseline to 12 mo.CONCLUSION The use of HCL in real-world clinical practice for one year was associated with significant improvements in A1C,%TIR,physical functioning,hypoglycemia fear,emotional distress,and emotional burden related to diabetes management.However,these changes were not associated with time in auto mode.