Construction and self-activation detection of yeast two-hybrid bait plasmid of human programmed cell death ligand 1 immunoglobulin variable region domain gene / 中国生物制品学杂志

@#Objective To construct a yeast two-hybrid recombinant bait plasmid of human programmed cell death ligand 1(PD-L1)immunoglobulin variable region(IgV)domain gene,detect its expression in yeast and detect the cytotoxicity and self-activation of PD-L1 IgV protein as well as the interaction between PD-L1 IgV and human thioredoxin(hTrx).Methods Human PD-L1 was analyzed by bioinformatics method,and primers were designed to amplify PD-L1 IgV domain based on the coding region of PD-L1 gene registered in NCBI GenBank database. PCR amplification was carried out with pENTERPD-L1 plasmid as template,and then cloned into yeast two-hybrid bait vector pGBKT7. The recombinant bait plasmid and pGBKT7 empty vector were transformed into Y2HGold yeast cells respectively,and the PD-L1 IgV gene and its expression were detected by PCR and Western blot;Meanwhile,the protein toxicity and self-activation of PD-L1 IgV were detected,and the interaction between PD-L1 IgV and hTrx was detected by drip plate method.Results The bioinformatics analysis results of PD-L1 were consistent with related reports. The recombinant bait plasmid pGBKT7-PD-L1 IgV was correctly constructed,and Y2HGold positive clone was obtained,in which PD-L1 IgV was stably expressed. The empty vector pGBKT7 and recombinant bait plasmid pGBKT7-PD-L1 IgV grew well on SD/-Trp and SD/-Trp/X-α-Gal plates with the same colony size and number and white colony,but they did not grow on SD/-Trp/X-α-Gal/AbA plates,which indicated that PD-L1 IgV protein had no toxicity and no self-activation effect on yeast. The results of drip plates test showed that all experimental groups grew well on SD/-Trp/-Leu plate,while only positive control group grew on SD/-Trp/-Leu/X-α-Gal/AbA plate and showed blue color,which indicated that bait protein PD-L1 IgV and hTrx did not self-activate,and there was no interaction between them.Conclusion Recombinant human PD-L1 IgV bait plasmid was successfully constructed. PD-L1 IgV protein showed no toxicity and self-activation effect on yeast cells,and there was no interaction between PD-L1 IgV and hTrx. Subsequently,hTrx can be used to construct a peptide aptamer library,from which peptide aptamers that specifically bind to PD-L1 IgV can be screened.

Minimally Invasive Direct Coronary Artery Bypass and Percutaneous Coronary Intervention Followed by Transcatheter Aortic Valve Implantation: A Promising Concept in High?risk Octogenarians

Objectives: In this article, we present our initial clinical experience with staged minimally invasive direct coronary bypass (MIDCAB), percutaneous coronary intervention (PCI), and transcatheter aortic valve implantation (TAVI) in high?risk octogenarians (Hybrid). Background: The use of percutaneous techniques for managing structural heart diseases, especially in elderly high?risk patients, has revolutionized the treatment of structural heart diseases. These procedures are present predominantly being offered as isolated interventions. The feasibility, clinical benefit, and outcomes of combining these techniques with MIDCAB have not been sufficiently explored and have subsequently been underreported in the contemporary literature. Methods: Four consecutive octogenarians with severe aortic stenosis (AS) and complex coronary artery disease (CAD) that were at high risk for conventional surgery with extracorporeal circulation (ECC) were discussed in our Multidisciplinary Heart Team(MDH). Our MDH consisted of an interventional cardiologist, cardiac surgeon, and cardiac anesthesiologist. A hybrid approach with the alternative strategy comprising of MIDCAB, PCI, and TAVI in a staged fashion was agreed on. All 4 patients had both PCI/stenting and MIDCAB prior to deployment of the TAVI?prosthesis. Results: From January 2019 to December 2020, 4 consecutive patients aged between 83 and 85 (3male/1 female) years were scheduled for MIDCAB/ PCI followed by percutaneous treatment of severe symptomatic AS. Intraoperatively, one patient was converted to full sternotomy, and surgery was performed by off?pump coronary artery bypass grafting. The overall procedural success rate was 100% in all 4 patients with resolution of their initial presenting cardiopulmonary symptoms. There were no severe complications associated with all hybrid procedures. There was no 30?day mortality in all patients. All patients were discharged home with a median hospital stay ranging between 9 and 25days. All patients have since then been followed?up regularly. There was one noncardiac?related mortality at 6?months postsurgery. All other patients were well at 1?year follow?up with improved NewYork Heart Association Class II. Conclusions: In a selected group of elderly, high prohibitive risk patients with CAD and severe symptomatic AS, a staged approach with MIDCAB and PCI followed by TAVI can be safely performed with excellent outcomes. We advocate a MDH?based preliminary evaluation of this patient cohort in selecting suitable patients and appropriate timing of each stage of the hybrid procedure.

Potential larvicidal bioefficacy of copper sulfide-based hybrid nanoemulsions of eucalyptus oil against Aedes aegypti (Linnaeus)

Background & objectives: Nanotechnology, an emerging field, has acquired considerable attention for the control of vectors. The present study aimed to synthesize, characterize copper sulfide- and eucalyptus oil-based hybrid nanoemulsions and investigate their larvicidal potential against Aedes aegypti by studying larvicidal bioassay, morphological aberrations, histopathological alterations, biochemical analysis and evaluation of risk assessment in non-target organisms. Methods: Hybrid nanoemulsions were prepared by mixing aqueous copper sulfide nanoparticles (CuSNPs) with non-polar eucalyptus oil in five ratios (1:1, 1:2, 1:3, 1:4 and 1:5) by sonication, screened and characterized using Transmission electron microscopy (TEM). Larvicidal activity was recorded and toxicity values were calculated by log-probit method. Morphological, histological and biochemical changes were examined in Aedes aegypti larvae after treatment. Nanohybrids were also tested under simulated conditions and against non-target organism. Results: The nanohybrid ratio of 1:5 was found to be stable after thermodynamic stability tests. TEM studies revealed average size of 90±7.90 nm with globular shape. LC50 and LC90 toxicity values of prepared CuSNPs were calculated out to be 5.00 and 5.81ppm after 24 hours treatment. Effective concentration of prepared nanohybrid (6.5ppm) tested under simulated conditions showed maximum larvicidal mortality after 48 hours of exposure. No toxicity towards the Mesocyclops spp. was observed after treatment of these nanohybrids even up to 21 days. Interpretation & conclusion: Copper sulfide based hybrid nanoemulsions were found to show efficient larvicidal property which can be used for the formulation of ecofriendly bio-larvicide against Aedes aegypti.

Monitoria acadêmica no curso de medicina: o desenvolvimento de um ensino híbrido como estratégia para integrar o discente ingressante em tempos pós pandêmicos: um relato de experiência / Academic monitoring in the medical course: the development of a hybrid teaching as a strategy to integrate the entering student in post-pandemic times: an experience report / Seguimiento académico en la carrera de medicina: el desarrollo de una enseñanza híbrida como estrategia de integración del alumno de nuevo ingreso en tiempos post- pandémicos: relato de una experiencia

No período pós pandêmico o retorno às aulas se deu em modelos distintos, dentre eles, o híbrido, capaz de utilizar da melhor forma os recursos presentes, tanto na educação presencial, quanto na não-presencial. O presente trabalho é um relato de experiência com o objetivo de descrever a participação, como discente monitor, de três acadêmicos do curso de Medicina da Universidade Federal da Integração Latino- Americana no projeto "Monitoria Acadêmica em Programa de Integração Ensino Serviço Comunidade I como estratégia para integrar o estudante ingressante", relatando o uso de ferramentas digitais no ensino híbrido como método de superação das barreiras temporais e espaciais e de engajamento discente. Nesse sentido, evidenciou-se maior flexibilidade de acesso dos discentes ingressantes à monitoria acadêmica pela introdução do ensino híbrido, contribuindo para o processo de adaptação à vida acadêmica. Ainda, o uso de ferramentas digitais se mostrou um facilitador do processo de sistematização e internalização das informações e vivências. Por fim, o fator de maior relevância na integração dos discentes foi a promoção de ambientes abertos a questionamentos com coordenação horizontal e rede de apoio, sejam eles presenciais ou não.

In the post-pandemic period, the return to classes took place in different models, among them the hybrid model, capable of making the best use of the resources present in both face-to-face and non-presential education. The present work is an experi- ence report with the objective of describing the participation, as a student monitor, of three students from the Medicine course of the Federal University of Latin American Integration in the project "Academic Monitoring in the Program for Integration Teaching- Community Service I as a strategy to integrate the entering student", reporting the use of digital tools in hybrid teaching as a method to overcome temporal and spatial barriers and to engage the students. In this sense, there was evidence of greater flexibility of access of the incoming students to academic monitoring through the introduction of hybrid tea- ching, contributing to the process of adaptation to academic life. Still, the use of digital tools proved to be a facilitator of the process of systematization and internalization of information and experiences. Finally, the most relevant factor in the integration of stu- dents was the promotion of open environments with horizontal coordination and support network, whether face-to-face or not.

En el período post-pandémico, el regreso a clases se dio en diferentes mo- delos, entre ellos el híbrido, capaz de aprovechar al máximo los recursos presentes en la enseñanza presencial y no presencial. El presente trabajo es un relato de experiencia con el objetivo de describir la participación, como alumno monitor, de tres estudiantes del curso de Medicina de la Universidad Federal de Integración Latinoamericana en el pro- yecto "Seguimiento Académico en Programa de Integración Docente Servicio Comuni- tario I como estrategia de integración del alumno ingresante", dando cuenta del uso de herramientas digitales en la educación híbrida como método de superación de las barreras temporales y espaciales y de compromiso del alumno. En este sentido, se evidenció una mayor flexibilidad de acceso de los estudiantes al seguimiento académico por la introdu- cción de la enseñanza híbrida, contribuyendo al proceso de adaptación a la vida acadé- mica. Aún así, el uso de herramientas digitales demostró ser un facilitador del proceso de sistematización e internalización de información y experiencias. Finalmente, el factor más relevante en la integración de los estudiantes fue la promoción de ambientes abiertos al cuestionamiento con coordinación horizontal y red de apoyo, presencial o no.

Mechanical behavior of different machinable ceramic crowns using vertical and horizontal preparations: an in-vitro study / Comportamento mecânico de diferentes coroas cerâmicas usináveis usando preparos verticais e horizontais: um estudo in vitro

Objective: the aim of this study was to compare the mechanical behavior of different ceramics when used in thin vertical preparations versus traditional horizontal preparation. Material and Methods: two stainless-steel dies were milled to simulate a minimally invasive vertical preparation (VP) and a traditional horizontal preparation (HP) for an all-ceramic crown of a maxillary first premolar. The stainless-steel dies were duplicated using epoxy resin. Eighty monolithic crowns were milled and divided into 2 groups according to preparation design. Each design group was subdivided into 4 sub-groups according to material (n=10): IPS e.max CAD (lithium disilicate), Bruxzir shaded zirconia (full contour zirconia), CeraSmart (resin nanoceramic) and CEREC Tessera (advanced lithium disilicate). The crowns were cemented on their relevant epoxy resin dies using self-adhesive resin cement. All specimens were subjected to 15,000 thermocycles and then loaded to fracture in a universal testing machine. Data were analyzed using two-way ANOVA and Tukey pair wise comparison test. Results: the fracture resistance mean values of the VP (1344 + 118 N) was significantly lower than the HP design (1646 + 191 N). Ceramic crowns made of full contour zirconia had higher fracture resistance mean values (2842 + 380 N) than advanced lithium disilicate (1272 + 125 N) followed by lithium disilicate crowns (983 + 52 N) and resin nanoceramic (882 + 61 N). Conclusion: both vertical and horizontal preparations, regardless the different ceramic materials, showed clinically acceptable fracture resistance values. (AU)

Objetivo: o objetivo deste estudo foi comparar o comportamento mecânico de diferentes cerâmicas quando utilizadas em preparos verticais finos ou preparos horizontais tradicionais. Material e Métodos: dois modelos de aço inoxidável foram fresados para simular um preparo vertical minimamente invasivo (PV) e um preparo horizontal tradicional (PH) para uma coroa totalmente em cerâmica de um primeiro pré-molar superior. As matrizes de aço inoxidável foram duplicadas usando resina epóxi. Oitenta coroas monolíticas foram fresadas e divididas em 2 grupos de acordo com o desenho do preparo. Cada grupo foi subdividido em 4 subgrupos de acordo com o material (n=10): IPS e.max CAD (dissilicato de lítio), zircônia Bruxzir (zircônia de contorno total), CeraSmart (resina nanocerâmica) e CEREC Tessera (dissilicato de lítio avançado). As coroas foram cimentadas em suas respectivas matrizes de resina epóxi usando cimento resinoso autoadesivo. Todos os espécimes foram submetidos a 15.000 ciclos térmicos e então carregados até a fratura em uma máquina de teste universal. Os dados foram analisados usando ANOVA com dois fatores e teste de comparação por pares de Tukey. Resultados: os valores médios de resistência à fratura do PV (1344 + 118 N) foram significativamente menores do que PH (1646 + 191 N). As coroas de cerâmica feitas de zircônia de contorno total apresentaram maiores valores médios de resistência à fratura (2842 + 380 N) do que dissilicato de lítio avançado (1272 + 125 N), seguido por coroas de dissilicato de lítio (983 + 52 N) e resina nanocerâmica (882 + 61 N). Conclusão: preparos verticais e horizontais, independentemente dos diferentes materiais cerâmicos, apresentaram valores de resistência à fratura clinicamente aceitáveis. (AU)

Application of the "quaternity" hybrid digital teaching method in the standardized residency training of clinical pathology / 中华医学教育探索杂志

Based on the limitations of certain conditions in the traditional clinical pathology teaching, this paper puts forward the "quaternity" hybrid digital teaching reform practice of clinical medicine, imaging, anatomy and pathology content. This teaching method can optimize the teaching process and improve the teaching efficiency. The specific advantages of this teaching method are as follows: the digital materials of different modules of clinical practice, imaging, anatomy and pathology are integrated to make the teaching content more perfect; it is helpful to improve the cognition of resident doctors on the pathological characteristics and the overall characteristics of the disease, and promote their thinking ability of clinicopathological integration; the combination of hybrid digital teaching and various teaching methods, including clinical pathology discussion, makes teaching more free and is conducive to classroom learning and self-learning. This paper discussed the construction and application of the "quaternity " hybrid digital teaching mode, and provided new ideas and methods for clinical pathology teaching and talent training.

Comparison of faculty and student evaluations of the hybrid teaching of orthopedics during the COVID-19 pandemic

Background@#In the face of the COVID-19 pandemic and a country-wide lockdown, the University of the Philippines College of Medicine halted face-to-face teaching in exchange for online learning for its students. For the Learning Unit VI students, clinical rotations shifted to hybrid activities to continue learning activities while minimizing exposure risk. The Philippine General Hospital Department of Orthopedics introduced the following hybrid activities in its curriculum for Learning Unit VI students: 1) Online Lectures, 2) Online Departmental Conference, 3) Online Division Rounds, 4) Online SGDs, 5) Written Case, 6) Online Exams, 7) Preceptorship, Demo, Return Demo, and 8) Online OSCE. The department used a variety of platforms including synchronous sessions, asynchronous pre-recorded lectures, and face-to-face teaching, as appropriate. @*Objectives@#The study compared the faculty and student course evaluations of activities in the hybrid ORTHO 251 course. @*Methodology@#Faculty and students were asked to evaluate each activity according to the Course Evaluation By Students (CEBS), the standard questionnaire used by the college, to determine the overall rating of each activity as well as any differences between the two groups. @*Results@#The hybrid activities conducted in the ORTHO 251 course were rated as good or excellent by the faculty and students, with differences in a few activities. Consultants rated online exams as being less effectively integrated and that there was inadequate time allotment for online SGDs, written cases, and online exams. Meanwhile, students rated all activities higher in terms of stimulating self-directed learning. @*Conclusion@#With good to excellent outcomes, this study found that it has at least satisfactorily matched the learning platform to the learning component. While knowledge may be taught via asynchronous recorded lectures or reading materials, attitude and thinking processes are better formed through synchronous discussion. Skills in medical education, including Orthopedics, are still best taught via face-to-face demoreturn demo. With this information, the department can investigate the causes of these differences and improve on the identified weaknesses.

The Performance of Graduation from Traditional Growing Rods with Apical Control Technique in Patients with Congenital Early-Onset Scoliosis / 罕见病研究

  Objective  Different from other etiologies of early-onset scoliosis (EOS), congenital early-onset scoliosis (CEOS) is mainly linked to vertebral anomalies, such as formation failures and segmentation failures at the apex segments. So far, there is little research on CEOS patients who have completed traditional growing rods (TGR) treatment, and the initial outcomes of TGR with or without apical control technique (ACT) are different. Therefore, we compared the "final" results of CEOS patients who completed TGR treatment with or without ACT.  Methods  We conducted a retrospective study of CEOS patients who completed TGR treatment from 2007—2020. They either had final fusion or were followed up after reaching skeletal maturity. We split the patients into two groups based on whether they had ACT with TGR or not. The ACT-TGR group had apical vertebrectomy/hemivertebrectomy with short fusion and TGR. The TGR-only group had only TGR. We looked at their demographic features, radiographic measurements, and complications.  Results  This study enrolled 46 CEOS patients, of which 13 patients were in the ACT-TGR group and 33 patients in the TGR group. The ACT-TGR group had a longer distraction interval (1.17 years vs. 0.75 years). The ACT-TGR group had a larger preoperative main curve [87.00(63.50, 98.00)], but the residual curve degrees were comparable between the two groups at the last follow-up (P=0.354). At the last follow-up, the T1-12 and T1-S1 heights were similar between the two groups. The ACT-TGR group had a lower number of implant-related complications per patient (0.77 vs. 1.48). Three patients in the ACT-TGR group underwent final fusion, while 17 patients in the TGR group underwent final fusion (P=0.060).  Conclusions  Both ACT-TGR and traditional TGR coud effectively correct deformity and preserve spinal growth in CEOS patients. ACT-TGR had a better corrective effect on patients with severe deformity and did not have a significant impact on spinal height. For patients with acceptable correction, spontaneous fusion and without implant failure, retaining the implant and continuing observation could be a strategy for graduating from growing rod treatment.

A hybrid home rehabilitation program for Moyamoya Disease to facilitate return to work and functional independence: A case report from a developing country during the COVID-19 pandemic

@#A 35-year-old female, right-handed, non-hypertensive, and non-diabetic Filipino presented with decreased verbal output and weakness of the right upper and lower extremities during the peak of the COVID-19 pandemic. Cerebral angiography showed bilateral steno-occlusive disease, which was consistent with Moyamoya disease. She underwent inpatient rehabilitation consisting of physical, occupational, and speech therapy. Rehabilitation posthospital discharge was continued using a hybrid rehabilitation approach with a mixed in-person home rehabilitation and remote telerehabilitation. The hybrid approach helped ensure continuity of rehabilitation care, minimize travel and exposure to the hospital or community amid the COVID-19 risks, and reduce costs, without entirely losing the benefits that could only be obtained from hands-on therapeutic evaluation and treatment. After six months of hybrid rehabilitation, the patient was able to return to work and regain functional independence.

Peripheral brain access in small group discussion in anatomy

Background and Objective@#The pandemic has forced medical education to adopt online and hybrid set-ups, and this has greatly changed the way human anatomy is taught. Course-required knowledge can be accessed using raw references like original publications, collected reviews such as those found in books, as well as in shorter versions like summaries, and in online or electronic applications or software. With readily accessible online physical materials and human resources in anatomy, the value of learning by seeking out verifiable information to answer a real time query may change the current method of teaching and assessment of outcome-based learning in a heavy-recall subject such as human anatomy. For the student, sources of information or instruction are termed the “peripheral brain”. The objective of this study is to describe the medical students’ method in accessing medical information during a hybrid small group discussion.@*Methods@#In a modified hybrid laboratory set-up, a class of 200 students were divided into 18 groups, with two students in each group acting as laboratory dissector, who will broadcast their in-person classroom activities to the group members via zoom. The groups rotated in nine specimen stations consisting of soft-embalmed cadavers, plastinated specimen, models, bones, and VH dissector™ virtual dissector. Students were allowed to use any type of resources to accomplish the following tasks: 1) look for listed structures, 2) identify landmarks, and 3) describe functions. A Google sheet survey was administered a month after the activity on the following domains: search strategy, targeted references, and verifiability of information. @*Results@#There were 110 students with age range of 19-27 years old, who participated in the study. Their most accessed reference is still personally prepared notes, followed by electronic books. When using ebooks, the first thing students reported exploring is the table of contents, followed by the search button. If doing online search, the key word used is the structure or function of interest. In group dynamics, students prefer to divide the work and assign tasks to each member, instead of collectively and simultaneously discussing a topic. For them, the most important characteristic of a reliable peripheral brain is that it is the recommended reference, followed by how current the reference is, i.e., published in the last 3 to 5 years. Interestingly, for most students, the information must be acquired in 5 minutes, which is contrary to the preferred mode of reference. Artificial intelligence may enhance SGDs according to most of the students. In accessing peripheral brain, Google is perceived as the quickest, books are most reliable, and Pubmed is the most up-to-date. Most of the students preferred pre-assigned questions or tasks during SGDs, with equal distribution of work. Giving and receiving remote instructions is not a problem. Dealing with a difficult group member is important, but is not a problem in hybrid discussion. @*Conclusion@#The survey results provide valuable insight on learning strategies used by the current generation of medical students, who have started medical school during the pandemic and are used to online teachinglearning modes of instruction. These findings can be exploited in designing course activities. The concept of peripheral brain in small group discussions can be formally introduced to students learning anatomy to utilize modern technology in enhancing knowledge.

Robot-assisted minimally invasive coronary artery bypass in treating multi-vessel coronary artery disease: A retrospective study in a single center / 中国胸心血管外科临床杂志

@#Objective    To evaluate the early and mid-term results of robot-assisted coronary artery bypass grafting (RACAB) in the treatment of multi-vessel coronary artery disease (MV-CAD). Methods     Patients with MV-CAD who underwent RACAB from April 2018 to December 2021 in our hospital were included. Patients who underwent hybrid coronary revascularization (HCR) which combined RACAB with percutaneous coronary intervention were allocated to a HCR-RACAB group, and patients who underwent multi-vessel RACAB were allocated to a MV-RACAB group. Perioperative and follow-up data were collected and compared between the two groups. Results     A total of 102 patients were included, including 81 males and 21 females with a mean age of 61.7±10.8 years. Two (2.0%) patients were transferred to conventional CABG due to sudden ventricular fibrillation and pleura adhesion. In the remaining 100 patients who underwent RACAB, 100 left internal mammary arteries (LIMA) and 46 right internal mammary arteries (RIMA) were harvested with a 100.0% success rate. Besides, all patients undergoing RACAB achieved LIMA/RIMA-left anterior descending branch reconstruction, with an average number of 2.5±0.6 target vessels revascularized by stent or graft. One patient had perioperative myocardial infarction with an outcome of death. The incidence of major perioperative adverse events was 1.0%. There was no perioperative stroke or re-sternotomy for hemostasis. The mean follow-up time was 28.2 months, with a follow-up rate of 99.0% and an overall major adverse cardiac and cerebrovascular event (MACCE) rate of 7.0%, including 3 all-cause deaths (3.0%), 2 strokes (2.0%) and 3 re-revascularizations (3.0%). The HCR-RACAB group had fewer red blood cell transfusion (P=0.030) and intraoperative blood loss (P=0.037) compared with the MV-RACAB group, and there was no statistical difference in the incidence of major perioperative adverse events or MACCE between the two groups during the follow-up period (P>0.05). Conclusion    RACAB can be safely applied in the treatment of MV-CAD with good early and mid-term outcomes. High-quality harvesting of LIMA/RIMA and aortic no-touch technique are crucial to achieve these results.

Screening and optimization of the formulation of human recombinant neutrophil inhibitory factor and hirulog hybrid for injection / 中国生物制品学杂志

@#Objective To screen and optimize the formulation and technology of human recombinant neutrophil inhibitory factor and hirulog hybrid(TNHH)for injection,and investigate its stability.Methods Based on the results of the single factor experiment,with the pH range,mannitol dosage and povidone K30 dosage as independent variables,and the content of high molecular protein as response value,the response surface design(CCF)test was used to analyze the effects of the respective variables and their interaction on the content of high molecular protein in TNHH for injection to screen out the optimal formulation. In order to facilitate the operation,the optimal formulation was adjusted to prepare three batches of samples in pilot scale,which were placed at 40 ℃,75% relative humidity(RH)for 2,4 weeks and 2 ～ 8 ℃ for 3,6 months,respectively. The samples were taken and the appearance,pH,purity of reversed phase-high performance liquid chromatography(RP-HPLC)and purity of size exclusion chromatography-high performance liquid chromatography(SECHPLC)were detected to verify the stability of this formulation and process.Results The optimal formulation was pH 4. 982 6,mannitol 7. 986 4% and povidone K30 1. 902 7%,which was finally adjusted to pH 5. 0,mannitol 8. 0% and povidone K302. 0%. The TNHH preparation for injection prepared by the optimized prescription and process were stable in quality and met the clinical medication requirements.Conclusion The optimum formulation of TNHH preparation for injection is reasonable in the process and suitable for industrial production.

Lipid-polymer hybrid nanoparticle with cell-distinct drug release for treatment of stemness-derived resistant tumor

Drug resistance presents one of the major causes for the failure of cancer chemotherapy. Cancer stem-like cells (CSCs), a population of self-renewal cells with high tumorigenicity and innate chemoresistance, can survive conventional chemotherapy and generate increased resistance. Here, we develop a lipid-polymer hybrid nanoparticle for co-delivery and cell-distinct release of the differentiation-inducing agent, all-trans retinoic acid and the chemotherapeutic drug, doxorubicin to overcome the CSC-associated chemoresistance. The hybrid nanoparticles achieve differential release of the combined drugs in the CSCs and bulk tumor cells by responding to their specific intracellular signal variation. In the hypoxic CSCs, ATRA is released to induce differentiation of the CSCs, and in the differentiating CSCs with decreased chemoresistance, DOX is released upon elevation of reactive oxygen species to cause subsequent cell death. In the bulk tumor cells, the drugs are released synchronously upon the hypoxic and oxidative conditions to exert potent anticancer effect. This cell-distinct drug release enhances the synergistic therapeutic efficacy of ATRA and DOX with different anticancer mechanism. We show that treatment with the hybrid nanoparticle efficiently inhibit the tumor growth and metastasis of the CSC-enriched triple negative breast cancer in the mouse models.

All-stage targeted therapy for the brain metastasis from triple-negative breast cancer

Brain metastasis is a common and serious complication of breast cancer, which is commonly associated with poor survival and prognosis. In particular, the treatment of brain metastasis from triple-negative breast cancer (BM-TNBC) has to face the distinct therapeutic challenges from tumor heterogeneity, circulating tumor cells (CTCs), blood-brain barrier (BBB) and blood-tumor barrier (BTB), which is in unmet clinical needs. Herein, combining with the advantages of synthetic and natural targeting moieties, we develop a "Y-shaped" peptide pVAP-decorated platelet-hybrid liposome drug delivery system to address the all-stage targeted drug delivery for the whole progression of BM-TNBC. Inherited from the activated platelet, the hybrid liposomes still retain the native affinity toward CTCs. Further, the peptide-mediated targeting to breast cancer cells and transport across BBB/BTB are demonstrated in vitro and in vivo. The resultant delivery platform significantly improves the drug accumulation both in orthotopic breast tumors and brain metastatic lesions, and eventually exhibits an outperformance in the inhibition of BM-TNBC compared with the free drug. Overall, this work provides a promising prospect for the comprehensive treatment of BM-TNBC, which could be generalized to other cell types or used in imaging platforms in the future.

Application of continuous nursing based on hybrid electronic platform and fragmented time concept in out-of-hospital rehabilitation of patients with anterior cruciate ligament reconstruction / 中国实用护理杂志

Objective:To explore the application effect of continuous nursing based on hybrid electronic platform and fragmentation time in the out-of-hospital rehabilitation of patients with anterior cruciate ligament reconstruction.Methods:This was a randomized controlled study. From April 2020 to October 2021, a total of 90 patients undergoing anterior cruciate ligament reconstruction in Weifang People′s Hospital were selected as the research objects by convenience sampling. Forty patients from April to December 2020 were selected as control group, and 45 patients from January to October 2021 were selected as intervention group. The control group implemented routine discharge guidance and follow-up, while the intervention group was given continuous nursing plan based on the concept of hybrid electronic platform and fragmented time. Before operation and 1, 3 and 6 months after operation, the knee range of motion and Lysholm score of patients in the two groups were analyzed. At 1, 3 and 6 months after operation, the rehabilitation exercise compliance score, self-efficacy score and knee stability examination of the two groups were analyzed.Results:A total of 41 patients in each group completed the study. At 1 month after operation, the knee range of motion, Lysholm score, rehabilitation exercise compliance score and self-efficacy score of intervention group were (96.46 ±3.58) ° and (53.54 ± 6.57), (69.17 ± 6.27), (4.01 ± 0.38) points, respectively. In the control group, they were (89.02 ± 4.22)° and (45.02 ± 7.61), (56.78 ± 8.45), (3.61 ± 0.42) points. At 3 months after operation, they were (136.83 ± 4.30)° and (72.76 ± 4.96), (60.71 ± 5.87), (4.97 ± 0.32) points in the intervention group, (133.54 ± 3.58)° and (69.83 ± 6.65), (56.73 ± 8.57), (4.83 ± 0.45) points in the control group, respectively. At 6 months after operation, they were (139.39 ± 1.99)° and (85.61 ± 6.11), (57.71 ± 7.41), (6.58 ± 0.96) points in the intervention group, (138.29 ± 2.65)° and (81.80 ± 6.38), (47.90 ± 6.02), (6.35 ± 1.23) points in the control group, respectively. The knee range of motion, Lysholm score and rehabilitation exercise compliance score of the intervention group were better than those of the control group at 1, 3 and 6 months after operation, and the differences were statistically significant ( t values were 2.12-8.61, all P<0.05). The self-efficacy score of the intervention group was higher than that of the control group at 1 month after operation, and the difference was statistically significant ( t=4.57, P<0.05). Conclusions:The continuous nursing program based on hybrid electronic platform and fragmented time can improve the knee function of patients with anterior cruciate ligament reconstruction in the early postoperative period, improve the compliance of rehabilitation exercise and the level of early self-efficacy.

Research progress in the application of hybrid cell membrane biomimetic nano-drug delivery system in cancer treatment / 国际生物医学工程杂志

The biomimetic strategy of using the cell membrane-coated nanoparticles can retain the physical and chemical properties of the nanoparticles and show the biological characteristics of the source cell membrane, which can further enhance the role of the nanodrug in tumor treatment. A hybrid cell membrane is the fusion of two or more different types of cell membranes. A hybrid cell membrane can endow nanoparticles with multiple biofunctions derived from the source cells compared with a single cell membrane. Hybrid cell membranes provide a foundation to stimulate extensive research into multifunctional biomimetic nano-drug delivery system (NDDS), which is expected to broaden the application of biomimetic nanotechnology in drug delivery systems. In this review paper, the types of hybrid cell membrane used to construct nano-drug delivery systems, the preparation and characterization methods, and cancer treatment research progress in recent years were reviewed.

Biomechanical Study on Contiguous Three-Level Cervical Hybrid Surgery and Anterior Cervical Discectomy and Fusion / 医用生物力学

Objective To compare the biomechanical effects of contiguous three-level cervical Hybrid surgery[anterior cervical discectomy and fusion (ACDF) + cervical disc arthroplasty ( CDA)] and three-level ACDF. Methods The finite element model of C1-T1 cervical-thoracic spine was developed based on CT data. Three models were simulated by the implantation of Prestige LP and Zero-P prostheses, including two Hybrid models (AFA, Prestige LP implanted at C3-4 and C5-6 segments and Zero-P implanted at C4-5 segment; FAF, Zero-P implanted at C3-4 and C5-6 segments and Prestige LP implanted at C4-5 segment) and three-level ACDF model(FFF). The changes in range of motion (ROM) of adjacent levels during flexion, extension, lateral bending and axial rotation, the overall ROM, as well as the intradiscal pressure ( IDP) and facet contact force ( FCF) of adjacent levels were compared. Results The ROM in adjacent levels and the overall ROM of the AFA modelwere closer to the intact model, and the maximum increases in the ROM of the adjacent levels for the FAF and FFF models were 15. 0% and 23. 4% , respectively. For AFA, FAF and FFF models, the maximum increases in the maximum IDP of adjacent levels were 19. 0% , 66. 7% , 147. 6% , and the maximum increases in FCF were 17. 4% , 55. 7% , 80. 1% , respectively. Conclusions This study provides biomechanical basis for three-level cervical Hybrid surgery in treating patients with the contiguous three-level cervical degenerative disc disease.

Advance on small molecule self-assembled nano-drug delivery system / 药学学报

Since the application of biomedical nanotechnology in the field of drug delivery breathes new life into the research and development of high-end innovative agents, a substantial number of novel nano-drug delivery systems (nano-DDSs) have been successively developed and applied in the clinical practice. Among them, small molecule pure drug and prodrug-based nanoassemblies have grasped great attention, owing to the facile fabrication, ultrahigh drug loading and feasible industrial production. Herein, we provide an overview on the latest updates of small-molecule nanoassemblies. Firstly, the self-assembled prodrug-based nano-DDSs are introduced, including nanoassemblies formed by amphiphilic monomeric prodrugs, hydrophobic monomeric prodrugs and dimer monomeric prodrugs. Then, the recent advances on nanoassemblies of small molecule pure chemical drugs and biological drugs are presented. Furthermore, carrier-free small-molecule hybrid nanoassemblies of pure drugs and/or prodrugs are summarized and analyzed. Finally, the rational design, application prospects and clinical challenges of small-molecule self-assembled nano-DDSs are discussed and highlighted. This review aims to provide scientific reference for constructing the next generation of nanomedicines.

Identification of anti-Mycobacterium tuberculosis agents targeting the interaction of bacterial division proteins FtsZ and SepFe

Tuberculosis (TB) is one of the deadly diseases caused by Mycobacterium tuberculosis (Mtb), which presents a significant public health challenge. Treatment of TB relies on the combination of several anti-TB drugs to create shorter and safer regimens. Therefore, new anti-TB agents working by different mechanisms are urgently needed. FtsZ, a tubulin-like protein with GTPase activity, forms a dynamic Z-ring in cell division. Most of FtsZ inhibitors are designed to inhibit GTPase activity. In Mtb, the function of Z-ring is modulated by SepF, a FtsZ binding protein. The FtsZ/SepF interaction is essential for FtsZ bundling and localization at the site of division. Here, we established a yeast two-hybrid based screening system to identify inhibitors of FtsZ/SepF interaction in M. tuberculosis. Using this system, we found compound T0349 showing strong anti-Mtb activity but with low toxicity to other bacteria strains and mice. Moreover, we have demonstrated that T0349 binds specifically to SepF to block FtsZ/SepF interaction by GST pull-down, fluorescence polarization (FP), surface plasmon resonance (SPR) and CRISPRi knockdown assays. Furthermore, T0349 can inhibit bacterial cell division by inducing filamentation and abnormal septum. Our data demonstrated that FtsZ/SepF interaction is a promising anti-TB drug target for identifying agents with novel mechanisms.

mRNA delivery in cancer immunotherapy

Messenger RNA (mRNA) has drawn much attention in the medical field. Through various treatment approaches including protein replacement therapies, gene editing, and cell engineering, mRNA is becoming a potential therapeutic strategy for cancers. However, delivery of mRNA into targeted organs and cells can be challenging due to the unstable nature of its naked form and the low cellular uptake. Therefore, in addition to mRNA modification, efforts have been devoted to developing nanoparticles for mRNA delivery. In this review, we introduce four categories of nanoparticle platform systems: lipid, polymer, lipid-polymer hybrid, and protein/peptide-mediated nanoparticles, together with their roles in facilitating mRNA-based cancer immunotherapies. We also highlight promising treatment regimens and their clinical translation.