Search

Objective: To construct polydopamine (PDA)-based nanoparticles (NPs) for combined chemotherapy (CT) and photothermal therapy (PTT) of thyroid tumors by conjugating doxorubicin (DOX) via Schiff base reaction and decorating with RGD peptide. Methods: PDA NPs were synthesized using dopamine hydrochloride (DA) as the raw material and reacted with DOX-PEG-NH2 to obtain PDA-DOX NPs. Subsequently, RGD peptide was coupled with PDA-DOX NPs for modification. Their size, charge, and shape were characterized using DLS and SEM. The assembly of DOX was verified by ultraviolet–visible spectroscopy (UV–Vis), and the release efficiency of DOX under different pH conditions was calculated. The antitumor effect of RGD@PDA-DOX was validated in KTC-1 cells and tumor-bearing nude mice. Results: The prepared RGD@PDA-DOX exhibited excellent dispersion, stability, and biocompatibility. PDA-DOX possessed superior photothermal conversion efficiency, capable of rapidly elevating the solution temperature within 5 min. In vitro studies revealed that the inhibitory rate of RGD@PDA-DOX combined with 808 nm laser on KTC-1 cells reached 92% (p < 0.05). In vivo experiments demonstrated that RGD@PDA-DOX exhibits no cytotoxicity. The modification with RGD peptides enables RGD@PDA-DOX to target tumor regions and accumulate over an extended period. Additionally, RGD@PDA-DOX, when combined with an 808 nm laser, significantly inhibits tumor growth. Conclusion: RGD@PDA-DOX can effectively accumulate in tumor regions and demonstrates excellent anti-tumor efficacy. It may serve as a feasible approach for the effective treatment of thyroid tumors, providing further evidence and data for clinical translation. [ABSTRACT FROM AUTHOR]

Programmed cell death represents a precisely regulated and active cellular demise, governed by a complex network of specific genes and proteins. The identification of multiple forms of programmed cell death has significantly advanced the understanding of its intricate mechanisms, as demonstrated in recent studies. A thorough grasp of these processes is essential across various biological disciplines and in the study of diseases. Nonetheless, despite notable progress, the exploration of the relationship between programmed cell death and disease, as well as its clinical application, are still in a nascent stage. Therefore, further exploration of programmed cell death and the development of corresponding therapeutic methods and strategies holds substantial potential. Our review provides a detailed examination of the primary mechanisms behind apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis. Following this, the discussion delves into biological functions and diseases associated dysregulated programmed cell death. Finally, we highlight existing and potential therapeutic targets and strategies focused on cancers and neurodegenerative diseases. This review aims to summarize the latest insights on programmed cell death from mechanisms to diseases and provides a more reliable approach for clinical transformation. [ABSTRACT FROM AUTHOR]

Abstract Objective To construct polydopamine (PDA)-based nanoparticles (NPs) for combined chemotherapy (CT) and photothermal therapy (PTT) of thyroid tumors by conjugating doxorubicin (DOX) via Schiff base reaction and decorating with RGD peptide. Methods PDA NPs were synthesized using dopamine hydrochloride (DA) as the raw material and reacted with DOX-PEG-NH2 to obtain PDA-DOX NPs. Subsequently, RGD peptide was coupled with PDA-DOX NPs for modification. Their size, charge, and shape were characterized using DLS and SEM. The assembly of DOX was verified by ultraviolet–visible spectroscopy (UV–Vis), and the release efficiency of DOX under different pH conditions was calculated. The antitumor effect of RGD@PDA-DOX was validated in KTC-1 cells and tumor-bearing nude mice. Results The prepared RGD@PDA-DOX exhibited excellent dispersion, stability, and biocompatibility. PDA-DOX possessed superior photothermal conversion efficiency, capable of rapidly elevating the solution temperature within 5 min. In vitro studies revealed that the inhibitory rate of RGD@PDA-DOX combined with 808 nm laser on KTC-1 cells reached 92% (p

Biomaterials play an integral role in treatment of external auditory canal (EAC) diseases. Regarding the special anatomic structure and physiological characteristics of EAC, careful selection of applicable biomaterials was essential step towards effective management of EAC conditions. The bioactive materials can provide reasonable biocompatibility, reduce risk of host pro-inflammatory response and immune rejection, and promote the healing process. In therapeutic procedure, biomaterials were employed for covering or packing the wound, protection of the damaged tissue, and maintaining of normal structures and functions of the EAC. Therefore, understanding and application of biomaterials was key to obtaining great rehabilitation in therapy of EAC diseases. In clinical practice, biomaterials were recognized as an important part in the treatment of different EAC diseases. The choice of biomaterials was distinct according to the requirements of various diseases. As a result, awareness of property regarding different biomaterials was fundamental for appropriate selection of therapeutic substances in different EAC diseases. In this review, we firstly introduced the characteristics of EAC structures and physiology, and EAC pathologies were summarized secondarily. From the viewpoint of biomaterials, the different materials applied to individual diseases were outlined in categories. Besides, the underlying future of therapeutic EAC biomaterials was discussed.

With the improvement of micromanufacturing technology and the further elucidation of the propulsion mechanism, the manufacture and application of micro/nanomotors have made great progress. However, the application of micro/nanomotors in translational medicine is still in its infancy, and the promise of its research remains to be fully realized. In this paper, the preparation status of micro/nanomotors and their application prospects in translational medicine were reviewed. The representative micro/nanomotors and their clinical application value were introduced. In addition, this paper also analyzes the possible reasons for the low clinical conversion rate of micro/nanomotors and proposes the current challenges and future prospects to indicate a direction for their translational application in medicine. [ABSTRACT FROM AUTHOR]

Abstract Programmed cell death represents a precisely regulated and active cellular demise, governed by a complex network of specific genes and proteins. The identification of multiple forms of programmed cell death has significantly advanced the understanding of its intricate mechanisms, as demonstrated in recent studies. A thorough grasp of these processes is essential across various biological disciplines and in the study of diseases. Nonetheless, despite notable progress, the exploration of the relationship between programmed cell death and disease, as well as its clinical application, are still in a nascent stage. Therefore, further exploration of programmed cell death and the development of corresponding therapeutic methods and strategies holds substantial potential. Our review provides a detailed examination of the primary mechanisms behind apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis. Following this, the discussion delves into biological functions and diseases associated dysregulated programmed cell death. Finally, we highlight existing and potential therapeutic targets and strategies focused on cancers and neurodegenerative diseases. This review aims to summarize the latest insights on programmed cell death from mechanisms to diseases and provides a more reliable approach for clinical transformation.

Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.

With the development of clinical, basic medicine and metabolomics, intestinal flora has gradually become a focus of research and has been used in the diagnosis and treatment of several intestinal diseases. Lactobacillus can produce and regulate a variety of intestinal metabolites, and participate in lipid metabolism, thrombosis, inflammation and oxidative stress, and even ferroptosis, which may have an impact on the occurrence and development of cardiovascular diseases. This article reviews the role of lactobacillus in the regulation of metabolism, involvement in the pathophysiological mechanism of myocardial infarction and its clinical application in acute myocardial infarction, providing a new reference for the prevention and treatment of AMI. [ABSTRACT FROM AUTHOR]

Phototherapy (PT), including photodynamic therapy (PDT) and photothermal therapy (PTT), has recently achieved significant advances in antitumor and antiinfection therapy. Sonodynamic therapy (SDT), as a novel noninvasive therapy with a deeper penetration depth (>8 cm), fewer side effects and non-phototoxicity than PT, has drawn much attention in recent years. However, both PT and SDT have intrinsic limitations. By combining PT with SDT, the dualmodel therapy with advanced sensitizers overcome the intrinsic limitations and show higher efficacy than traditional monotherapy. Moreover, the photo-diagnosis modality could be easily integrated into synergistic therapy so that the sensitizer acts as a tracer for fluorescence/photoacoustic imaging, and the treatment process is visualized in a way that SDT combined with other therapies cannot achieve. This review summarizes the advanced sensitizers and the application of combination therapy, and explores the improvement strategies for promoting clinical transformation. [Display omitted] [ABSTRACT FROM AUTHOR]

The advantages of clinical application of 3D printing technology in orthopaedics have been gradually explored, showing a trend of vigorous development. However, throughout the country, there are still few hospitals and orthopedic surgeons who can apply 3D printing technology at a high level. This manuscript summarizes the application type, technical level, application field, clinical value, development conditions and application status of 3D printing technology in orthopaedic clinical application, analyzes the technical points and possible risks that should be paid attention to in the whole process of orthopaedic clinical application, and discusses the role of technology supply side, demand side and regulation side in the clinical promotion of 3D printing orthopaedics. The main reasons for the uneven development of 3D printing technology in various parts of the country are mainly due to the differences of technical mastery and application environment, while the crux of negative impact mainly lies in the insufficient understanding of doctors, lagging charging policy and indifference of the service market, which provide guidance in the popularization and application of 3D printing technology in orthopaedic clinic.

Microneedles are a patient-friendly technique for delivering drugs to the site of action in place of traditional oral and injectable administration. Silk fibroin represents an interesting polymeric biomaterial because of its mechanical properties, thermal stability, biocompatibility and possibility of control via genetic engineering. This review focuses on the critical research progress of silk fibroin microneedles since their inception, analyzes in detail the structure and properties of silk fibroin, the types of silk fibroin microneedles, drug delivery applications and clinical trials, and summarizes the future development trend in this field. It also proposes the future research direction of silk fibroin microneedles, including increasing drug loading doses and enriching drug loading types as well as exploring silk fibroin microneedles with stimulation-responsive drug release functions. The safety and effectiveness of silk fibroin microneedles should be further verified in clinical trials at different stages. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a lethal malignancy worldwide. Exosomes are extracellular vesicles derived from the endosomal pathway of nearly all cells and can be found in body fluids. They can be considered an intercellular system in the human body that can mediate near- and long-distance intercellular communication due to their features and functions. Investigations have revealed that exosomes are participated in different processes, physiologically and pathologically, especially in cancer. However, the clinical value of exosomes and their mechanisms of action in CRC are unclear and have not been systematically assessed. The purpose of this review is to discuss how exosomes play a role in the occurrence and development of CRC, with a particular focus on the functions and underlying mechanisms of tumor-derived exosomes as well as non-tumor-derived exosomes. We also describe the evidence that exosomes can be used as diagnostic and prognostic markers for CRC. In addition, the possibilities of exosomes in CRC clinical transformation are also discussed.

Xiaobin Shang,1,&ast; Yan Fang,2,&ast; Wenqiang Xin,3 Hongbo You1 1Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 352000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbo You, Email hongboyou2014@outlook.comAbstract: Osteoarthritis (OA) is a whole joint disease characterized by synovitis, cartilage destruction, and subchondral bone sclerosis and cyst. Despite decades’ study, effective treatment is rare for this chronic disease. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptosis bodies, are nano-sized vesicles with a cargo containing biologically active agents, such as nucleic acids, lipids, and proteins. As a group of short non-coding RNAs, microRNAs (miRNAs) can be delivered by parental cells secreted EVs. Negatively regulate the target mRNAs at the posttranscriptional level and regulate gene expression in recipient cells without modifying gene sequence. Recently, most studies focused on the function of EVs mediated miRNAs in the pathophysiological process of OA. However, all kinds of EVs specific and OA specific factors might influence the administration of EVs-miRNAs, especially the precise quantitative management. As a result, the flourishing of current research about EVs in the laboratory might not promote the relevant clinical transformation in OA treatment. In this review, we reviewed the present application of EVs-miRNAs in the therapeutic of OA and further analyzed the potential factors that might influence its application. Further progress in the quantitative management of EVs-miRNAs would accelerate the clinical transformation of miRNAs enriched EVs in the OA field.Keywords: osteoarthritis, extracellular vesicles, microRNAs, quantitative management, clinical transformation

Background: Patient-derived xenograft (PDX) models have shown a great efficiency in preclinical and translational applications. Gastrointestinal (GI) tumors have a strong heterogeneity, and the engraftment rate of PDX models remarkably vary. However, the clinicopathological and molecular characteristics affecting the engraftment rate still remain elusive. Methods: A total of 312 fresh tumor tissue samples from patients with GI cancer were implanted into immunodeficient mice. The median follow-up time of patients was 37 months. Patients' characteristics were compared in terms of PDX growth and overall survival. PDX models of 3-6 generations were used for drug evaluation. Results: In total, 171 (54.8%, 171/312) PDX models were established, including 85 PDX models of colorectal cancer, 21 PDX models of esophageal cancer, and 65 PDX models of gastric cancer. Other than tumor site, histology, differentiation degree, and serum alpha-fetoprotein (AFP) level, no significant differences were found between transplantation of xenografts and patients' characteristics. For patients who had undergone neoadjuvant therapy, the incidence of tumor formation was higher in those with progressive disease (PD) or stable disease (SD). In gastric cancer, the results showed a higher transplantation rate in deficient mismatch repair (dMMR) tumors, and Ki-67 could be an important factor affecting the engraftment rate. The gene mutation status of RAS and BRAF, two important molecular markers in colorectal cancer, showed a high degree of consistency between patients' tumors and PDXs. However, no significant effects of these two mutations on PDX engraftment rate were observed. More importantly, in this study although KRAS mutations were detected in two clinical cases, evident tumor inhibition was still observed after cetuximab treatment in both PDX models and patients. Conclusion: A large-scale PDXmodel including 171 caseswas successfully established for GI tumors in our center. The relationship between clinicopathological and molecular features and engraftment rates were clarified. Furthermore, this resource provides us with profound insights into tumor heterogeneity, making these models valuable for PDX-guided treatment decisions, and offering the PDX model as a great tool for personalized treatment and translation research. [ABSTRACT FROM AUTHOR]

The second near-infrared window (NIR-II) fluorescence imaging has been widely adopted in basic scientific research and preclinical applications due to its exceptional spatiotemporal resolution and deep tissue penetration. Among the various fluorescent agents, organic small-molecule fluorophores are considered the most promising candidates for clinical translation, owing to their well-defined chemical structures, tunable optical properties, and excellent biocompatibility. However, many currently available NIR-II fluorophores exhibit an "always-on" fluorescence signal, which leads to background noise and compromises diagnostic accuracy during disease detection. Developing NIR-II activatable organic small-molecule fluorescent probes (AOSFPs) for accurately reporting pathological changes is key to advancing NIR-II fluorescence imaging toward clinical application. This review summarizes the rational design strategies for NIR-II AOSFPs based on four core structures (cyanine, hemicyanine, xanthene, and BODIPY). These NIR-II AOSFPs hold substantial potential for clinical translation. Furthermore, the recent advances in NIR-II AOSFPs for NIR-II bioimaging are comprehensively reviewed, offering clear guidance and direction for their further development. Finally, the prospective efforts to advance NIR-II AOSFPs for clinical applications are outlined., (© 2024 Wiley‐VCH GmbH.)

Psoriasis is an immune-mediated, chronic, inflammatory systemic disorder with a decrease onthe quality of life. The interleukin-23 (IL-23)/IL-17 axis plays a crucial role in the pathogenesis of psoriasis. Im‐mune cells and various cytokines are involved, including interferon-α (IFN-α), tumor necrosis factor-α (TNF-α),IFN-γ, IL-12, IL-22, IL-23 and IL-17. Based on elucidated pathogenesis, biologics targeting TNF-α, IL-23, andIL-17 have been approved in the treatment of psoriasis and achieved satisfying efficacy. However, it' s still farfrom complete cure. At present, more therapeutic targets are under research or in clinical trials, such as JAK-STATpathway, aryl hydrocarbon receptor and Rho-associated kinase. This review summarizes therapeutic targets andbiologics of psoriasis and provides a reference for the clinical transformation of promising therapeutic targets.

Magnesium (Mg) is the fourth most abundant element in the human body and is important in terms of specific osteogenesis functions. Here, we provide a comprehensive review of the use of magnesium-based biomaterials (MBs) in bone reconstruction. We review the history of MBs and their excellent biocompatibility, biodegradability and osteopromotive properties, highlighting them as candidates for a new generation of biodegradable orthopedic implants. In particular, the results reported in the field-specific literature (280 articles) in recent decades are dissected with respect to the extensive variety of MBs for orthopedic applications, including Mg/Mg alloys, bioglasses, bioceramics, and polymer materials. We also summarize the osteogenic mechanism of MBs, including a detailed section on the physiological process, namely, the enhanced osteogenesis, promotion of osteoblast adhesion and motility, immunomodulation, and enhanced angiogenesis. Moreover, the merits and limitations of current bone grafts and substitutes are compared. The objective of this review is to reveal the strong potential of MBs for their use as agents in bone repair and regeneration and to highlight issues that impede their clinical translation. Finally, the development and challenges of MBs for transplanted orthopedic materials are discussed.

The therapeutic efficacy of drugs is determined, to a certain extent, by the efficiency of drug delivery. The low efficiency of drug delivery systems (DDSs) is frequently associated with serious toxic side effects and can even prove fatal in certain cases. With the rapid development of technology, drug delivery has evolved from using traditional frameworks to using nano DDSs (NDDSs), endogenous biomaterials DDSs (EBDDSs), and living cell DDSs (LCDDSs). LCDDSs are receiving widespread attention from researchers at present owing to the unique advantages of living cells in targeted drug delivery, including their excellent biocompatibility properties, low immunogenicity, unique biological properties and functions, and role in the treatment of diseases. However, the theoretical basis and techniques involved in the application of LCDDSs have not been extensively summarized to date. Therefore, this review comprehensively summarizes the properties and applications of living cells, elaborates the various drug loading approaches and controlled drug release, and discusses the results of clinical trials. The review also discusses the current shortcomings and prospects for the future development of LCDDSs, which will serve as highly valuable insights for the development and clinical transformation of LCDDSs in the future., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: The emergency department (ED) is a primary entry point of hospitals but does not have a system to identify and consult palliative care (PC) early in patients who meet criteria. Objectives: To determine the measurable effects of an ED PC consultation on patients who meet criteria, hypothesizing that ED PC consultation would lead to decreased average length of stay (ALOS), average direct cost per patient, decreased number of surgeries, and radiological tests performed per patient. Materials and Methods: A physician-led data-driven evidence-based algorithm was designed and piloted with implementation in two hospitals during January–March 2019 in Orlando, FL. A retrospective review of health record data was completed, comparing patients receiving PC consultation ordered in the ED versus those ordered after admission. Results: ED patients (n = 662) met PC criteria. PC consultation was ordered in ED for 80 (12.1%) cases. The following outcomes were lower for patients who received ED PC consultation than those who did not: ALOS by 6.4 days (6.74 vs. 13.14 days; p < 0.001), in-hospital mortality (12.5% vs. 19.1%; p = 0.11), surgery (11% vs. 37%; p < 0.01), radiological tests per patient (4.01 vs. 10.57; p < 0.001), and average direct cost per patient ($7,193 vs. $22,354). However, 30-day hospital revisit rates were relatively higher in those who did receive ED PC consultation than those who did not (20% vs. 13% p = 0.15). Conclusions: In this pilot project, PC patients can be identified in the ED with an algorithm that leads to earlier consultation and improved patient outcomes. Larger research trials are needed to replicate this strategy and results. [ABSTRACT FROM AUTHOR]

Peripheral nerve injuries (PNIs) frequently occur due to various factors, including mechanical trauma such as accidents or tool-related incidents, as well as complications arising from diseases like tumor resection. These injuries frequently result in persistent numbness, impaired motor and sensory functions, neuropathic pain, or even paralysis, which can impose a significant financial burden on patients due to outcomes that often fall short of expectations. The most frequently employed clinical treatment for PNIs involves either direct sutures of the severed ends or bridging the proximal and distal stumps using autologous nerve grafts. However, autologous nerve transplantation may result in sensory and motor functional loss at the donor site, as well as neuroma formation and scarring. Transplantation of Schwann cells/Schwann cell-like cells has emerged as a promising cellular therapy to reconstruct the microenvironment and facilitate peripheral nerve regeneration. In this review, we summarize the role of Schwann cells and recent advances in Schwann cell therapy in peripheral nerve regeneration. We summarize current techniques used in cell therapy, including cell injection, 3D-printed scaffolds for cell delivery, cell encapsulation techniques, as well as the cell types employed in experiments, experimental models, and research findings. At the end of the paper, we summarize the challenges and advantages of various cells (including ESCs, iPSCs, and BMSCs) in clinical cell therapy. Our goal is to provide the theoretical and experimental basis for future treatments targeting peripheral nerves, highlighting the potential of cell therapy and tissue engineering as invaluable resources for promoting nerve regeneration. [Display omitted] • Multi-dimensionally explore the role of Schwann cells in the process of peripheral nerve regeneration. • Summarize the signaling pathways of nerve regeneration. • Summarize the latest cellular therapeutic techniques, materials and cell types for nerve regeneration at the laboratory level. • Comprehensively provide the hurdles in clinical conversion of cell therapy. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is the fifth-ranked cancer worldwide with a relatively low five-year survival rate. Long non-coding RNAs are a group of RNAs with remarkable aberrant expression which could act on multiple bioprocesses and ultimately impact upon tumor proliferation, invasion, migration, metastasis, apoptosis, and therapy resistance in cancer cells including hepatocellular carcinoma cells. In recent years, long non-coding RNAs have been reported to be indispensable targets in clinical target therapy to stop the growth of cancer and prolong the lifespan of patients with hepatocellular carcinoma. In this review, we enumerate the signaling pathways and life activities affected by long non-coding RNAs in hepatocellular carcinoma cells to illustrate the role of long non-coding RNAs in the development and therapy resistance of hepatocellular carcinoma.

Hepatocellular carcinoma is the fifth-ranked cancer worldwide with a relatively low five-year survival rate. Long non-coding RNAs are a group of RNAs with remarkable aberrant expression which could act on multiple bioprocesses and ultimately impact upon tumor proliferation, invasion, migration, metastasis, apoptosis, and therapy resistance in cancer cells including hepatocellular carcinoma cells. In recent years, long non-coding RNAs have been reported to be indispensable targets in clinical target therapy to stop the growth of cancer and prolong the lifespan of patients with hepatocellular carcinoma. In this review, we enumerate the signaling pathways and life activities affected by long non-coding RNAs in hepatocellular carcinoma cells to illustrate the role of long non-coding RNAs in the development and therapy resistance of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Magnesium (Mg) is the fourth most abundant element in the human body and is important in terms of specific osteogenesis functions. Here, we provide a comprehensive review of the use of magnesium-based biomaterials (MBs) in bone reconstruction. We review the history of MBs and their excellent biocompatibility, biodegradability and osteopromotive properties, highlighting them as candidates for a new generation of biodegradable orthopedic implants. In particular, the results reported in the field-specific literature (280 articles) in recent decades are dissected with respect to the extensive variety of MBs for orthopedic applications, including Mg/Mg alloys, bioglasses, bioceramics, and polymer materials. We also summarize the osteogenic mechanism of MBs, including a detailed section on the physiological process, namely, the enhanced osteogenesis, promotion of osteoblast adhesion and motility, immunomodulation, and enhanced angiogenesis. Moreover, the merits and limitations of current bone grafts and substitutes are compared. The objective of this review is to reveal the strong potential of MBs for their use as agents in bone repair and regeneration and to highlight issues that impede their clinical translation. Finally, the development and challenges of MBs for transplanted orthopedic materials are discussed. [ABSTRACT FROM AUTHOR]

Due to the outbreak of novel coronavirus pneumonia, messenger RNA (mRNA) technology has attracted heated attention. A specific, safe, and efficient mRNA delivery system is needed. Lipid nanocarriers have become attractive carriers for mRNA delivery due to their high delivery efficiency, few side effects, and easy modification to change their structures and functions. To achieve the desired biological effect, lipid nanocarriers must reach the designated location for effective drug delivery. Therefore, the effects of the composition of lipid nanocarriers on their key properties are briefly reviewed. In addition, the progress of smart drug delivery by changing the composition of lipid nanocarriers is summarized, and the importance of component design and structure is emphasized. Subsequently, this review summarizes the latest progress in lipid nanocarrier-based mRNA technology and provides corresponding strategies for its current challenges, putting forward valuable information for the future design of lipid nanocarriers and mRNA., (© 2024 Wiley‐VCH GmbH.)

Although histologic analysis is the gold standard for diagnosing follicular lymphoma (FL) transformation, many patients are diagnosed with transformation by clinical factors as biopsy specimens often cannot be obtained. Despite the frequency of clinical diagnosis, no clinical assessment tool has yet been established for FL transformation in the rituximab era. We derived and validated a transformation scoring system (TSS) based on retrospective analyses of 126 patients with biopsy‐proven FL and histologic transformation (HT) at two hospitals of the National Cancer Center of Japan. In the derivation set (76 patients), the detailed analyses of the clinical characteristics at disease progression showed that lactate dehydrogenase (LDH) elevation, focal lymph nodal (LN) enlargement, hemoglobin <12 g/dl, and poor performance status (PS) (2‐4) were associated with HT. The weights of these variables were decided based on the regression coefficients. Next, we constructed a TSS encompassing the above four factors: LDH, (> upper limit of normal [ULN], ≤ULN ×2) (1 point), (≥ULN ×2) (2 points); focal LN enlargement, (≥3 cm, <7 cm) (1 point), (≥7 cm) (2 points); hemoglobin <12 g/dl (1 point); poor PS (2 points). We identified a high positive predictive value (PPV) (96.4%) and negative predictive value (NPV) (85.4%) for diagnosing HT when a cutoff score of 2 was selected for our TSS. In an external validation set (50 patients), the probability of HT was high with scores ≥2 (PPV, 93.3%; NPV, 82.9%). We developed a TSS that offers a simple, yet, valuable tool, for diagnosing HT, especially in patients who cannot undergo biopsy. [ABSTRACT FROM AUTHOR]

BACKGROUND: With the in-depth investigation of stem cells and better understanding of kidney ischemia/reperfusion injury, stem cell therapy for renal ischemia/reperfusion injury in animal experiments have been developed extensively, and have achieved certain advance. Therefore, it is necessary to conduct a systematic evaluation to explore the specific efficacy of stem cell therapy for renal ischemia/reperfusion injury. OBJECTIVE: To systematically evaluate the effects of stem cells on the function and structure of the kidney and the immune function of the body and the feasibility of transformation into clinical practice based on the animal experiments. METHODS: Databases of PubMed, Web of Science, Embase, CNKI, VIP and WanFang were searched by computer, and the search time was limited before May 2019. The literature was screened independently by two researchers, and the data were extracted. SYRCLE animal experiment bias risk assessment tool was used to evaluate the methodological quality of the study, and the evidence quality was evaluated using CERQual tool. RESULTS AND CONCLUSION: Finally, 17 animal experiments were included, but there was great clinical heterogeneity among the studies. Therefore, we performed a qualitative description. Compared with the placebo group, the renal function (serum creatinine and blood urea nitrogen level), immune status and renal tissue injury in the stem cell therapy group were improved. But the evidence quality of the six outcome indexes was “low”, and there was a certain risk of bias in the study. The exact efficacy of stem cells and the need for further clinical research cannot be determined due to the problems in experimental design and quality of evidence. Therefore, prior to the inception of clinical trial, high-quality pre-clinical study is necessary to further evaluate the effect of stem cells on renal ischemia/reperfusion injury and the feasibility of clinical transformation to reduce the risk of clinical transformation. [ABSTRACT FROM AUTHOR]

The biomedical research and healthcare delivery communities have increasingly come to focus their attention on the role of data and computation in order to improve the quality, safety, costs, and outcomes of both wellness promotion and care delivery. Depending on the scale of such efforts, and the environments in which they are situated, they are referred to variably as personalized or precision medicine, population health, clinical transformation, value-driven care, or value-based transformation. Despite the original intent of many efforts and publications that have sought to define personalized, precision, or data-driven approaches to improving health and wellness, the use of such terminology in current practice often treats said activities as discrete areas of endeavor within minimal cross-linkage across or between scales of inquiry. We believe that this current state creates numerous barriers that are preventing the advancement of relevant science, practice, and policy. As such, we believe that it is necessary to amplify and reaffirm our collective understanding that these fields share common means of inquiry, differentiated only by the units of measure being utilized, their sources of data, and the manner in which they are executed. Therefore, in this perspective, we explore and focus attention on such commonalities and then present a conceptual framework that links constituent activities into an integrated model that we refer to as a precision healthcare system. The presentation of this framework is intended to provide the basis for the types of shared, broad-based, and descriptive language needed to reference and realize such a framework. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are gaining recognition as potential therapeutic agents due to their small size, ability to target a wide range of genes, and significant role in disease progression. However, despite their promising potential, nearly half of the miRNA drugs developed for therapeutic purposes have been discontinued or put on hold, and none have advanced to phase III clinical trials. The development of miRNA therapeutics has faced obstacles such as difficulties in validating miRNA targets, conflicting evidence regarding competition and saturation effects, challenges in miRNA delivery, and determining appropriate dosages. These hurdles primarily arise from the intricate functional complexity of miRNAs. Acupuncture, a distinct, complementary therapy, offers a promising avenue to overcome these barriers, particularly by addressing the fundamental issue of preserving functional complexity through acupuncture regulatory networks. The acupuncture regulatory network consists of three main components: the acupoint network, the neuro-endocrine-immune (NEI) network, and the disease network. These networks represent the processes of information transformation, amplification, and conduction that occur during acupuncture. Notably, miRNAs serve as essential mediators and shared biological language within these interconnected networks. Harnessing the therapeutic potential of acupuncture-derived miRNAs can help reduce the time and economic resources required for miRNA drug development and alleviate the current developmental challenges miRNA therapeutics face. This review provides an interdisciplinary perspective by summarizing the interactions between miRNAs, their targets, and the three acupuncture regulatory networks mentioned earlier. The aim is to illuminate the challenges and opportunities in developing miRNA therapeutics. This review paper presents a comprehensive overview of miRNAs, their interactions with acupuncture regulatory networks, and their potential as therapeutic agents. By bridging the miRNA research and acupuncture fields, we aim to offer valuable insights into the obstacles and prospects of developing miRNA therapeutics. [ABSTRACT FROM AUTHOR]

This paper presents the results of a comparative study of the clinical symptoms of emotional burnout syndrome among 84 elderly women working in the specialty of physicians and 48 women who have officially ceased working in this specialty. The findings suggest that emotional burnout syndrome can take place in the elderly and is most closely associated with continued professional activity. The cessation of this working activity leads to stress, often with the subsequent development of posttraumatic stress disorder and stressinduced diseases. However, in this case, the clinical symptoms of emotional burnout syndrome do not disappear but are only transformed with joining of various psychosomatic disorders. Thus, the elderly who suffer from emotional burnout syndrome are a risk group as regards the formation and development of stress-associated diseases and require close attendance within the compulsory program of medical examination. [ABSTRACT FROM AUTHOR]

Luminescent monitoring of endogenous hydrogen peroxide (H 2 O 2 ) in tumors is conducive to understanding metastasis and developing novel therapeutics. The clinical transformation is obstructed by the limited light penetration depth, toxicity of nano-probes, and lack of long-term monitoring modes of up to days or months. New monitoring modes are introduced via specific probes and implantable devices, which can achieve real-time monitoring with a readout frequency of 0.01 s or long-term monitoring for months to years. Near-infrared dye-sensitized upconversion nanoparticles (UCNPs) are fabricated as the luminescent probes, and the specificity to reactive oxygen species is subtly regulated by the self-assembled monolayers on the surfaces of UCNPs. Combined with the passive implanted system, a 20-day monitoring of H 2 O 2 in the rat model of ovarian cancer with peritoneal metastasis is achieved, in which the limited light penetration depth and toxicity of nano-probes are circumvented. The developed monitoring modes show great potential in accelerating the clinical transformation of nano-probes and biochemical detection methods., (© 2023 Wiley-VCH GmbH.)

A review of the article "Quality Improvement into Practice" about quality improvement (QI) in nephrology nursing that was published in a 2020 issue is presented.

Background: Since the 2020 COVID-19 Pandemic struck the healthcare industry, there has been a rapidly evolving and escalating situation across the globe that lead healthcare organizations to embrace changes at an accelerated rate1. Hamad Medical Corporation (HMC) had to cope with an overwhelming number of patients being admitted to Acute Care areas during early 2021. When four HMC tertiary and secondary care hospitals were already at full capacity with COVID-19 patients, there was a need for another hospital like Al Wakra Hospital (AWH) to step up. AWH was a multi-specialty hospital attending to patients from all age groups with varying intensity levels in its Outpatient, Inpatient, and Critical Care Units. This article encompasses the journey of AWH from an acute care hospital to a COVID-19 facility receiving adult and obstetric COVID-19 patients from April 5th, 2021. Methods: The preparation involved rigorous risk assessment, brainstorming, and modification of patient care pathways and services (Table 1). A Series of Risk Assessment rounds were conducted. The transformation encompassed areas inclusive of, but are not limited to, the creation and implementation of clinical pathways, drop off and pick up points for ambulances, wayfinding creation, online/point-of-care/face-to-face education, installation of antigen testing/Sharps box/wall-mounted hand rubs/ACRYLIC screens, staff exposure interviews and test scheduling, personal protective equipment (PPE) availability, H2O2 vapor disinfection, and healthcare-associated infections surveillance2. Clinical pathways were well thought out to ensure the prevention of cross-contamination between patients3. Results: This transformation (Table1) demonstrated that successful change ensuring patient and staff safety can be achieved in a matter of days based on an organization's determination and comprehensive strategic planning, redesigning strategies that are effective, efficient, and befitting the need of time. Conclusion: A well-formulated infrastructure, prompt reallocation of resources, staff dedication, teamwork, proactive risk assessment, and continuous collaborative efforts paved the road to the successful clinical transformation of AWH. [ABSTRACT FROM AUTHOR]

The inflammatory response plays an important role in the onset, development and prognosis of inflammatory diseases and a variety of chronic diseases. Long-term uncontrolled inflammatory response may lead to dysfunction or loss of organ tissue function. Clinical practice and evidence-based medicine suggest that acupuncture can effectively alleviate the inflammatory status of various inflammatory diseases and chronic diseases. Stimulation of acupoints related to internal organs and target organs can initiate neuromodulation by modulating the microenvironment of acupoints. After integration of acupuncture stimulus information in the central nervous system, neurotransmitters, hormones, etc. are released and ultimately act on immune cells through neuro-endocrine-immune pathways, such as the vagus-mediated cholinergic anti-inflammatory pathway, vagus nerve-adrenal medullary-dopamine pathway, somatic sympathetic nerve pathway, and hypothalamic-pituitary-adrenal axis, etc. Ultimately, the intracellular signaling pathways and polarization balance of monocytes/macrophages and T cell subsets are regulated and the immune homeo-stasis of target organs of the body realizes. Therefore, we proposed that the anti-inflammatory action of acupuncture may be one of the universal therapeutic strategies for multiple diseases, and a powerful interpretation of acupuncture in regulating the balance of yin and yang. The elucidation of its anti-inflammatory action rules and mechanism may better realize the clinical transformation of acupuncture and moxibustion precision treatment.

The radiation therapy (RT) department at the British Columbia Cancer Agency - Vancouver Island Centre (VIC) is responsible for delivering radiation treatments to cancer patients from Vancouver Island, which has a population base of approximately 750,000. The purpose of this analysis is to examine a process transformation project undertaken by a VIC clinical champion using a sociotechnical approach and identify factors that influenced the project outcome. Beginning in January 2009, a radiation oncologist at VIC initiated a project to transform the clinical process of generating prescriptions for radiation therapy. The project objective was to replace the paper-based process for radiation therapy (RT) prescriptions with an electronic process to achieve benefits such as increased legibility, accuracy, and accessibility of prescriptions. The electronic prescription (e-Rx) process was designed and developed by health informatics students from the University of Victoria, and the new process was trialed and implemented for approximately half of the new patients seen by the VIC RT department. This pilot implementation was brought to a halt two weeks later, due to concerns raised by the RT department. Using a sociotechnical approach, the authors identify several factors that negatively impacted the project's successful implementation: lack of leadership endorsement and organizational strategy, insufficient formal and informal organizational power of the clinical champion, underestimation of complexity, and inadequate management of the implementation process. Although these factors have been well documented in the literature for large-scale system implementation projects, understanding the way by which they influence smaller-scale process transformation projects in highly specialized clinical settings may help future project managers and coordinators to set such projects up for success. [ABSTRACT FROM AUTHOR]

Healthcare technology continues to advance and be implemented in healthcare organizations. Nurse executives must strategically evaluate the effectiveness of each proposed system or device using a strategic planning process. Clinical information systems, computer-chip-based clinical monitoring devices, advanced Web-based applications with remote, wireless communication devices, clinical decision support software -- all compete for capital and registered nurse salary dollars. The concept of clinical transformation is developed with new models of care delivery being supported by technology rather than driving care delivery. Senior nursing leadership's role in clinical transformation and healthcare technology implementation is developed. Proposed standards, expert group action, business and consumer groups, and legislation are reviewed as strategic drivers in the development of an electronic health record and healthcare technology: A matrix of advancing technology and strategic decision-making parameters are outlined. [ABSTRACT FROM AUTHOR]