摘要：OBJECTIVE:To explore the most effective parameters of Yi Zhi Chan Tuina manipulation for improving peripheral blood ***:A total of 45 volunteers were recruited from Pudong district in Shanghai,China,from October to December 2010,and randomly divided into nine groups using computer-generated random *** received Yi Zhi Chan Tuina manipulation on Chengjin(BL 56) acupoint;each group received a particular combination of manipulation force and treatment *** used a two-factor,three-level factorial design to examine the effects of force and treatment time on changes in popliteal artery average volume flow,pulsatility index,and vessel diameter to determine the optimal parameter *** were assessed at baseline and after Tuina manipulation by interviewers blind to treatment group ***:After manipulation,two of the nine groups showed an increase in popliteal artery volume *** inter-participants effect test showed that for main effect of time,F = 0.331,P = 0.720;for main effect of force,F = 2.934,P = 0.066;and for the force-time interaction effect,F = 1.072,P = 0.385,indicating no interaction between force and ***,a pairwise comparison of the three levels of time showed that a treatment time of 10 min was significantly more effective than that of 2 min(P = 0.024).A pairwise comparison of light force,medium force,and heavy force showed a statistically significant effect for medium force(P = 0.035).CONCLUSION:Yi Zhi Chan Tuina manipulation with vertical force of 9.31 N for 10 min is most effective in improving peripheral circulation.

摘要：Three-dimensional(3D)bioprinting is a powerful approach that enables the fabrication of 3D tissue constructs that retain complex biological ***,the dense hydrogel networks that form after the gelation of bioinks often restrict the migration and proliferation of encapsulated ***,a sacrificial microgel-laden bioink strategy was designed for directly bioprinting constructs with mesoscale pore networks(MPNs)for enhancing nutrient delivery and cell *** sacrificial microgel-laden bioink,which contains cell/gelatin methacryloyl(GelMA)mixture and gelled gelatin microgel,is first thermo-crosslinked to fabricate temporary predesigned cell-laden constructs by extrusion bioprinting onto a cold ***,the construct is permanently stabilized through photo-crosslinking of *** MPNs inside the printed constructs are formed after subsequent dissolution of the gelatin *** MPNs allowed for effective oxygen/nutrient diffusion,facilitating the generation of bioactive ***,osteoblast and human umbilical vein endothelial cells encapsulated in the bioprinted large-scale constructs(≥1 cm)with MPNs showed enhanced bioactivity during *** 3D bioprinting strategy based on the sacrificial microgel-laden bioink provided a facile method to facilitate formation of complex tissue constructs with MPNs and set a foundation for future optimization of MPN-based tissue constructs with applications in diverse areas of tissue engineering.

摘要：The covalent attachment of protein-resistant polymers to therapeutic proteins is a widely used method for extending their in vivo half-lives; however, the effect of molecular weight of polymer on the in vitro and in vivo functions of protein-polymer conjugates has not been well elucidated. Herein we report the effect of molecular weight of poly（oligo（ethylene glycol） methyl ether methacrylate） （POEGMA） on the in vitro and in vivo properties of C-termi- nal interferon-alpha （IFN）-POEGMA conjugates. Increasing the molecular weight of POEGMA decreased the in vitro activity of IFN-ct but increased its thermal stability and in vivo pharmacokinetics. Intriguingly, the in vivo antitumor efficacy of IFN-a was increased by increasing the POEGMA molecular weight from ca. 20 to 60 kDa, but was not further increased by increasing the molecular weight of POEGMA from ca. 60 to 100 kDa due to the neutralization of the improved pharmacokinetics and the reduced in vitro activity. This finding offers a new viewpoint on the molecular size rationale for designing next-generation protein-polymer conjugates, which may benefit patients by reducing admin- istration frequency and adverse reactions, and improving therapeutic efficacy.

摘要：Glioblastoma (GBM) is the most common primary brain malignancy in adults and has a poor prognosis despite standard of care treatment. The mainstay of GBM treatment has relied on maximum surgical resection and chemotherapy and radiation. Cancer immunotherapy has made great strides since the advent of anti-PD-1, anti-CTLA-4, and other immune checkpoint inhibitors. With the advancement of novel therapeutics, more clinical trials for patients have opened as well. An important future direction of clinical trials is the ability to identify appropriate patients to optimize treatment response and minimize toxicities. This review describes considerations in designing future GBM clinical trials in not only immunotherapy but also with other promising treatments. We will discuss factors, such as pseudoprogression, genetic and circulating biomarkers, and the commensal microbiome of patients in the setting of clinical trial design.

摘要：New endoscopic techniques for hemostasis in nonvariceal bleeding were introduced and known methods further improved. Hemospray and Endoclot are two new compounds for topical treatment of bleeding. Initial studies in this area have shown a good hemostatic effect, especially in active large scale oozing bleeding, e.g., tumor bleedings. For further evaluation larger prospective studies comparing the substanced with other methods of endoscopic hemostasis are needed. For localized active arterial bleeding primary injection therapy in the area of bleeding as well as in the four adjacent quadrants offers a good method to reduce bleeding activity. The injection is technically easy to learn and practicable. After bleeding activity is reduced the bleeding source can be localized more clearly for clip application. Today many different through-thescope(TTS) clips are available. The ability to close and reopen a clip can aid towards good positioning at the bleeding site. Even more important is the rotatability of a clip before application. Often multiple TTS clips are required for secure closure of a bleeding vessel. One model has the ability to use three clips in series without changing the applicator. Severe arterial bleeding from vessels larger than 2 mm is often unmanageable with these conventional methods. Here is the over-the-scopeclip system another newly available method. It is similar to the ligation of esophageal varices and involves aspiration of tissue into a transparent cap before closure of the clip. Thus a greater vascular occlusion pressure can be achieved and larger vessels can be treated endoscopically. Patients with severe arterial bleeding from the upper gastrointestinal tract have a very high rate of recurrence after initial endoscopic treatment. These patients should always be managed in an interdisciplinary team of interventional radiologist and surgeons.

摘要：Herein,we report a geometrically well-defined prism assembled by two floxuridine(F)integrated RNA strands as a precise nanomedicine for chemodrug *** to the similarity between chemotherapeutic F and uridine(U),all uridines in the component RNA strands are replaced by F during their in vitro transcription *** specifically designing their sequences,F-containing S-shape tiles with the single-stranded loops are constructed and then further assemble into the RNA prism through T-junction interactions and sticky-end *** present study demonstrates that the F-integrated RNA prism can serve as an efficient platform for chemodrug delivery and anticancer *** believe that the study would help the future development of RNA-based nanomedicine in various applications.

摘要：Background:The nanotechnology boom and the ability to manufacture novel nanomaterials have led to increased production and use of engineered nanoparticles(ENPs).However,the increased use of various ENPs inevitably results in their release in or the contamination of the environment,which poses significant threats to human *** recent years,extraordinary economic and societal benefits of nanoproducts as well as their potential risks have been observed and widely *** estimate whether ENPs are safe from the onset of their manufacturing to their disposal,evaluation of the toxicological effects of ENPs on human exposure,especially on more sensitive and vulnerable sectors of the population(infants and children)is *** sources:Papers were obtained from PubMed,Web of Science,and Google *** search words included:"nanoparticles","infants","children","exposure","toxicity",and all relevant ***:A brief overview was conducted to 1)characterize potential exposure routes of ENPs for infants and children;2)describe the vulnerability and particular needs of infants and children about ENPs exposure;3)investigate the current knowledge about the potential health hazards of ENPs;and 4)provide suggestions for future research and regulations in ENP ***:As the manufacturing and use of ENPs become more widespread,directed and focused studies are necessary to measure actual exposure levels and to determine adverse health consequences in infants and children.

摘要：Objective： Injury and deficiency of the lacrimal duct epithelium （LDE） can lead to a variety of lacrimal diseases. The purpose of this study was to characterize potential candidate cells for constructing a tissue-engineered LDE. Methods： Different areas of the conjunctiva and lacrimal duct tissue were removed from male adult New Zealand white rabbits for histological evaluation. Hematoxylin and eosin staining and immunohistochemical staining of cytokeratin AEI＋AE3, cytokeratin 4, Ki-67, and MUC5AC were observed by light microscopy. The surface morphologies of different epithelial tissues and cellular structures were examined using field-emission scanning electron microscopy and transmission electron microscopy. Epithelial cells were isolated from tissues and identified by specific markers. In vitro, proliferative ability and Western blot analyses of the proliferating cell nuclear antigen （PCNA） of different epithelial cells cultured in identical environments were investigated and compared. Results： Histologically, the epithelial specific markers, cytokeratin AEI＋AE3 and cytokeratin 4, were expressed in the conjunctiva epithelium and the LDE. Notably, highly proliferative cells stained with Ki-67 were concentrated under the epithelium in a dome structure of the posterior palpebral conjunctiva. Differentiated goblet cells were also found to a lesser extent in this region. Primary palpebral and fornical conjunctival epithelial cells （PFCECs）, bulbar conjunctival epithelial cells （BCECs）, and lacrimal duct epithelial cells （LDECs） were successfully separated from tissues. In vitro, rabbit PFCECs and LDECs grew faster and expressed more PCNA than BCECs. Conclusions： PFCECs are anatomically similar to LDECs. They also have similar morphological characteristics, immune phenotypes, and proliferation features. PFCECs are therefore potential candidate cells to replace LDECs in tissue engineering to treat lacrimal duct diseases.

摘要：Miniature devices comprising stimulus-responsive hydrogels with high environmental adaptability are now considered competitive candidates in the fields of biomedicine,precise sensors,and tunable *** and advanced fabricationmethods are critical formaximizing the application capabilities ofminiature ***-based three-dimensional(3D)printing technology offers the advantages of a wide range of applicable materials,high processing accuracy,and strong 3D fabrication capability,which is suitable for the development of miniature devices with various *** paper summarizes and highlights the recent advances in light-based 3D-printed miniaturized devices,with a focus on the latest breakthroughs in lightbased fabrication technologies,smart stimulus-responsive hydrogels,and tunable miniature devices for the fields of miniature cargo manipulation,targeted drug and cell delivery,active scaffolds,environmental sensing,and optical ***,the challenges in the transition of tunable miniaturized devices from the laboratory to practical engineering applications are *** opportunities that will promote the development of tunable microdevices are elaborated,contributing to their improved understanding of these miniature devices and further realizing their practical applications in various fields.

摘要：Advances in biomimetic three-dimensional(3D) melanoma models have brought new prospects of drug screening and disease modeling, since their physiological relevancy for recapitulating in vivo tumor architectures is more accurate than traditional two-dimensional(2D) cell culture. Gelatin methacryloyl(GelMA) is widely used as a tissue-engineered scaffold hydrogel for 3D cell culture. In the present study, an in vitro 3D malignant melanoma model based on Gel MA was fabricated to evaluate the efficiency of hypericin(Hy)-loaded microemulsion(ME) in photodynamic therapy against melanoma. The ME was produced by the spontaneous emulsification method to enhance the bioavailability of Hy at tumor sites. Hy-loaded MEs were applied to a 3D malignant melanoma model made using 6% Gel MA and the co-culture of B16F10 and Balb/c 3T3 cells,followed by crosslinking using violet light(403 nm). The observation revealed excellent cell viability and the presence of F-actin cytoskeleton network. Hy-loaded MEs exhibited higher phototoxicity and cell accumulation(about threefold) than free Hy, and the cells cultured in the 3D system displayed lower susceptibility(about 2.5-fold) than those in 2D *** findings indicate that the developed MEs are potential delivery carriers for Hy;furthermore, Gel MA hydrogel-based modeling in polydimethylsiloxane(PDMS) molds is a user-friendly and cost-effective in vitro platform to investigate drug penetration and provide a basis for evaluating nanocarrier efficiency for skin cancer and other skin-related diseases.