Systematic characterization and identification of the chemical constituents of the Schisandra chinensis decoction based on a hybrid scanning technique of UHPLC/IM-QTOF-MS / 药学学报

italic>Schisandra chinensis is a traditional Chinese medicine with the functions of reinforcing deficiency, strengthening, and inducing astringency, appliable to treat the chronic cough and deficiency in breath, palpitation, and insomnia, etc. A hybrid mass spectrometry scanning strategy (high-definition data-independent/data-dependent acquisition, HDDIDDA), enabling the ion mobility separation and alternating data-independent acquisition/data-dependent acquisition, was established, which, in combination with in-house library-driven automatic peak annotation workflows facilitated by the UNIFI software, was utilized to systematically characterize the multi-classes of chemical components from S. chinensis. The use of an HSS T3 column (100 mm × 2.1 mm, 1.8 μm), 0.1% formic acid in H2O-acetonitrile as the mobile phase running at the flow rate of 0.3 mL·min-1, and column temperature at 35 ℃, could enable good separation of the S. chinensis components within 42 min. HDDIDDA scan in both the positive and negative ion modes was employed for data acquisition. Based on the automatic peak annotation, reference standards comparison, MS2 data interpretation, and literature analysis, we were able to identify or tentatively characterize 105 compounds in the S. chinensis decoction, involving 56 terpenoids, 42 lignans, five glycosides, one organic acid, and one flavonoid. HDDIDDA scanning can improve the coverage of data acquisition and improve the accuracy of identification, while CCS prediction analysis provides the possibility to distinguish isomers by the ion mobility technology. The results provide reference for the intelligent material basis research of TCM.

Case Study on Deductive Teaching of "Doctor-patient Communication" / 中国医学伦理学

By introducing the connotation of deductive teaching and analyzing the significance of early contact clinical course of "doctor-patient communication", the author reinterpreted the educational concept of deductive teaching combined with the characteristics of medical humanities, and reformed the early contact clinical course of "doctor-patient communication" by introducing deductive teaching method. Taking the early contact clinical course of "doctor-patient communication" of a medical university as an example, the teaching framework was designed to share experience from three aspects: teaching content, teaching process and teaching effect evaluation. At the same time, combined with the characteristics of the course and the needs of students, found out the problems encountered in the teaching process, and put forward constructive opinions and strategies, in order to provide theoretical and practical reference for the teaching of medical humanities course.

Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H2O2-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H+ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H2O2-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

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.

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.

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.

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.

Effects of R-loops on Genome Stability / 中国生物化学与分子生物学报

The R-loop is a three-stranded nucleic acid structure, which consists of a RNA: DNA hybrid and a DNA single strand. R-loop can be divided into two types: physiological and pathological. The physiological R-loop is involved in many physiological processes such as DNA replication, transcription, and gene expression regulation, while the pathological R-loop induces DNA damage and genome rearrangement. There are many factors that affect the formation of R-loops. Unregulated R-loops destroy genomic stability by interfering with DNA replication and double-strand DNA break repair, and can cause cancer. Therefore, the regulation of R-loops is very important. RNA/ DNA helicase Senataxin (SETX), DEAD-box helicase 5 (DDX5), ribonuclease H (RNase H) and DNA topoisomerase I (topo) play an important role in regulating the balance of R-loops in vivo. Among them, SETX is one of the most characteristic R-loop decomposing enzymes, which can dissolve the R-loops produced during transcriptional termination sites, replication-transcriptional conflicts and DNA damage repair. Senataxin mutations will lead to ataxia with eye movement apraxia type 2 (AOA2) and amyotrophic lateral sclerosis type 4 (ALS4). Currently there are still many unsolved issues, although many in-depth studies of R-loops have been carried out. Therefore, the structure and function of physiological and pathological R-loops still need to be further explored. This review mainly focuses on the definition and classification of R-loops, the factors that affect the formation of R-loops, the influence of R-loops on genomic stability and R-loop-related diseases, and explores the possibility of using R-loops as a therapeutic target in the future.

Visual Detection of Plant Viral RNA Based on Gold Nanoparticles and Hybrid Chain Reaction / 中国生物化学与分子生物学报

The harm of plant virus disease is serious, which significantly restricts the sustainable development of agriculture and can cause huge economic losses. Monitoring plant health and early detection of viral pathogens are essential to reduce the spread of disease. Therefore, in order to realize the early detection of plant viral diseases in the field, a sensitive, specific and efficient colorimetric visual technique for plant viral RNA was designed by combining the colorimetric method based on gold nanoparticles (AuNPs) and hybrid chain reaction (HCR). In this study, tobacco mosaic virus (TMV) was used as a model to design two hairpin structures H1/ H2 with single-stranded tails based on TMV-specific conserved fragments. TMV could open the hairpin structure to alternately form long double-straight DNA. The binding difference between AuNPs and two nucleic acid states before and after HCR reaction resulted in colorimetric signal generation, thus realizing visual detection of TMV. After optimizing the concentration of Tris-HAc, the concentration of hairpin structure and the reaction time of HCR, the best detection conditions were obtained. The sensitivity and specificity of the technique were analyzed and real samples were tested under optimal conditions. The results showed that the absorbance ratio of AuNPs (A

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.

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.

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.