Clinical Application Research Articles

Characteristics of moxibustion in Dragon Gate Stone Inscription prescriptions

The Dragon Gate Stone Inscription prescriptions are the earliest surviving stone inscriptions of medical formulas in China, covering various departments such as internal medicine, surgery, gynecology, pediatrics and ophthalmology. By reviewing 28 moxibustion prescriptions recorded in the Dragon Gate Stone Inscriptions, the following application characteristics are summarized: moxibustion mainly treats acute diseases such as mania, deficiency-cold syndrome, and jaundice; in terms of point selection, specific points such as the thirteen ghost points, eight influential points, and front-mu points are used, emphasizing the extraordinary meridians such as governor vessel and conception vessel, as well as specific single acupoints with unique therapeutic effects; in clinical application, it follows the principle of treating according to syndrome differentiation, uses multiple acupoints simultaneously, employs food-medicine homology, and adjusts the moxibustion dosage according to individual conditions. The Dragon Gate Stone Inscription prescriptions reflect that the application of moxibustion therapy during the Northern Wei to Tang Dynasty period had already reached a relatively mature level, indicating a high level of proficiency in moxibustion techniques during that time.

Combination of acupuncture therapy and kinesiotherapy: an example of pain rehabilitation

The effect mechanism and the characteristics of clinical application of the combination of acupuncture therapy and kinesiotherapy are explored for pain rehabilitation. Analgesia of acupuncture therapy and kinesiotherapy is characterized by multiple targets and dimensions. The paper summarizes the effect mechanisms of these two therapies and their synergistic action and investigates the current situation and clinical characteristics of their combination in treatment of musculoskeletal pain, visceral pain and postoperative pain so that the references can be provided for the selection of pain rehabilitation programs.

Probiotics intervention for type 2 diabetes mellitus therapy: a review from proposed mechanisms to future prospects.

Type 2 diabetes mellitus (T2DM) is one of the metabolic diseases with the highest morbidity rates in the world. Probiotics have positive health impacts on human health and a considerable amount of research has demonstrated their beneficial effects in treating T2DM. However, probiotic intervention in T2DM has complex mechanisms because the pathogenesis of T2DM is complex. This review summarized the mechanisms of probiotic intervention in diabetes from the perspective of diabetes pathogenesis. First, the objectives of probiotic intervention in diabetes aimed at the intestinal tract reparative effects, pancreatic function, host metabolism and self-recovery were comprehensively reviewed. Next, we concluded the clinical application status of ingested probiotics in patients with T2DM, and an obvious imbalance exists between theoretical probiotic research and clinical applications. Finally, we summarized the emerging research on probiotic interventions in T2DM and analyzed the literature in this regard, including next-generation probiotics; suggestions for probiotics consumption with the aim of diabetic complications; as well as the association between novel mechanisms of diabetes remission with the potential for probiotic intervention. In conclusion, this review sheds light on the potential role of probiotics, from proposed mechanisms to prospects in relieving T2DM.

Emotion-related Processes Between Parents and Adolescents: Evidence for Bidirectional Effects over Time.

Parent emotion socialization has long been studied in relation to children's socioemotional adjustment. Little attention has been paid to how parents' socialization responses are shaped by youth characteristics over time, such as emotional lability. The present study explored the mutual influence between parent emotion socialization and adolescent emotional lability. Participants were 87 adolescents (M = 14.23 years old, SD = .50; 50 girls) and their parents, who completed questionnaires at three time points from 8th grade through 10th grade. Hierarchical linear modeling demonstrated mutual influences between parent emotion socialization and adolescent emotional lability, with relations moderated by adolescent gender. Increases in parents' reward of negative emotion predicted decreased emotional lability in girls. Parents' increased magnification of negative emotions corresponded to decreased emotional lability in boys. Boys' increases in emotional lability predicted decreased parental magnification of negative emotions over time. Increases in parents' magnification of negative emotions predicted increased emotional lability in girls. Girls' increases in emotional lability corresponded to increased parental magnification over time. There were no longitudinal effects of adolescent emotional lability on parents' reward, override, and punishment of negative emotions. Future directions and clinical applications are discussed.

(SiFA)SeFe: A Hydrophilic Silicon-Based Fluoride Acceptor Enabling Versatile Peptidic Radiohybrid Tracers.

The radiohybrid (rh) concept to design targeted (and chemically identical) radiotracers for imaging or radionuclide therapy of tumors has gained momentum. For this strategy, a new bifunctional Silicon-based Fluoride Acceptor (SiFA) moiety (SiFA)SeFe was synthesized, endowed with improved hydrophilicity and high versatility of integration into rh-compounds. Preliminary radiolabeling and stability studies under different conditions were conducted using model bioconjugate peptides. Further, three somatostatin receptor 2 (sstR2)-targeted rh-compounds ((SiFA)SeFe-rhTATE1-3, TATE = (Tyr3)-octreotate) were developed. Compound (SiFA)SeFe-rhTATE3, enables labeling with 18F for PET imaging or chelation of 177Lu for therapy. The rh-compounds possess comparable receptor binding affinity and in vitro performance as good as the clinically proven gold standards. SstR2-specificity was further shown for (SiFA)SeFe-rhTATE2 using the chicken chorioallantoic membrane (CAM) model. The biodistribution of two compounds in mice showed high accumulation in tumors and excretion via the kidneys, demonstrating the clinical applicability of the (SiFA)SeFe moiety.

Zinc Coordination Lipid Nanoparticles Co-Delivering Calcium Peroxide and Chelating STING agonist for Enhanced Cancer Metalloimmunotherapy.

Metalloimmunotherapy has achieved great preclinical success against malignant tumors. Nonetheless, the limited immune cell infiltration and impaired immunogenicity within the tumor microenvironment (TME) significantly hinder its translation to clinical applications. In this study, a zinc coordination lipid nanoparticle is developed loaded with calcium peroxide hydrate (CaO2) nanoparticles and the STING agonist diABZI-2, which is termed A-CaO2-Zn-LNP. The release of Zn2+ from the A-CaO2-Zn-LNP and the calcium overload synergistically induced immunogenic cell death (ICD). In addition, CaO2 nanoparticles can consume H+ and release oxygen (O2) under acidic conditions. This treatment increased the pH and alleviated the hypoxia of the TME. Along with cGAS-STING activation by diABZI-2, A-CaO2-Zn-LNP ultimately results in enhanced anti-tumor systemic immunity and long-term immune memory via alleviating the immunosuppressive microenvironment. Taken together, A-CaO2-Zn-LNP offers a new nanoplatform that expands its application for cancer treatment by metalloimmunotheray.

Reference ranges of peripheral-muscle oxygenation in term neonates delivered by Caesarean section during immediate transition after birth.

To establish reference ranges of peripheral-muscle regional oxygen saturation (prSO2) and peripheral fractional tissue oxygen extraction (pFTOE) during the first 15 min after birth in stable term neonates. Secondary outcome parameters of prospective observational studies in healthy term neonates delivered by Caesarean section were analysed. prSO2 was measured on the right forearm using the INVOS 5100C monitor. pFTOE was calculated out of prSO2 and arterial oxygen saturation (SpO2). Centile charts (10th-90th) of prSO2 and pFTOE were defined during the first 15 min after birth. Three-hundred-five term neonates with a mean gestational age and birth weight of 39.0 ± 0.9 weeks and 3321 ± 454 g, respectively, were included. The 50th centiles of prSO2 were 39% (minute two), 52% (minute five), 71% (minute 10), and 73% (minute 15). The 50th centiles of pFTOE were 0.529 (minute two), 0.378 (minute five), 0.237 (minute 10), and 0.231 (minute 15). Reference ranges of prSO2 and pFTOE were established for term neonates delivered by Caesarean section during the immediate transition after birth. These reference ranges increase knowledge of physiological processes taking place immediately after birth and are necessary for possible future clinical applications.

A review: artificial intelligence in image-guided spinal surgery.

Due to the complex anatomy of the spine and the intricate surgical procedures involved, spinal surgery demands a high level of technical expertise from surgeons. The clinical application of image-guided spinal surgery has significantly enhanced lesion visualization, reduced operation time, and improved surgical outcomes. This article reviews the latest advancements in deep learning and artificial intelligence in image-guided spinal surgery, aiming to provide references and guidance for surgeons, engineers, and researchers involved in this field. Our analysis indicates that image-guided spinal surgery, augmented by artificial intelligence, outperforms traditional spinal surgery techniques. Moving forward, it is imperative to collect a more expansive dataset to further ensure the procedural safety of such surgeries. These insights carry significant implications for the integration of artificial intelligence in the medical field, ultimately poised to enhance the proficiency of surgeons and improve surgical outcomes.

(+)4-cholesten-3-one/sodium alginate/gelatin hydrogel for full-thickness wound repair and skin regeneration.

(+)4-cholesten-3-one has been proved to have potential wound healing effect in the process of wound regeneration. This study aimed to evaluate the effect of (+)4-cholesten-3-one/sodium alginate/gelatin on skin injury and reveal its potential molecular mechanism. First, we prepared sodium alginate/gelatin hydrogel (SA/Gel hydrogel) with different ratios and tested their characteristics. Based on these results, different concentrations of (+)4-cholesten-3-one were added into SA/Gel hydrogel. A full-thickness skin injury model was successfully established to evaluate wound healing activityin vivo. HE staining and Masson staining were used to evaluate the thickness of granulation tissue and collagen deposition level. Immunohistochemical staining and immunofluorescence staining were applied to detect the level of revascularization and proliferation in each group of wounds. Western blot, quantitative-PCR and immunofluorescence staining were used to detect the expression of proteins related to Wnt/β-catenin signaling pathway in each group of wounds.In vitroresults showed that the hydrogel not only created a 3D structure for cell adhesion and growth, but also exhibited good swelling ability, excellent degradability and favorable bio-compatibility. Most importantly,in vivoexperiments further indicated that (+)4-cholesten-3-one/SA/Gel hydrogel effectively enhanced wound healing. The effectiveness is due to its superior abilities in accelerating healing process, granulation tissue regeneration, collagen deposition, promoting angiogenesis, tissue proliferation, as well as fibroblast activation and differentiation. The underlying mechanism was related to the Wnt/β-catenin signaling pathway. This study highlighted that (+)4-cholesten-3-one/SA/Gel hydrogel holds promise as a wound healing dressing in future clinical applications.

Cloning and Functional Characterization of Novel Human Neutralizing Anti-IFN-α and Anti-IFN-β Antibodies.

Type I IFNs play a pivotal role in immune response modulation, yet dysregulation is implicated in various disorders. Therefore, it is crucial to develop tools that facilitate the understanding of their mechanism of action and enable the development of more effective anti-IFN therapeutic strategies. In this study, we isolated, cloned, and characterized anti-IFN-α and anti-IFN-β Abs from PBMCs of individuals treated with IFN-α or IFN-β, harboring confirmed neutralizing Abs. Clones AH07856 and AH07857 were identified as neutralizing anti-IFN-α-specific with inhibition against IFN-α2a, -α2b, and -αK subtypes. Clones AH07859 and AH07866 were identified as neutralizing anti-IFN-β1a-specific signaling and able to block lipopolysaccharide or S100 calcium-binding protein A14-induced IFN-β signaling effects. Cloned Abs bind rhesus but not murine IFNs. The specificity of inhibition between IFN-α and IFN-β suggests potential for diverse research and clinical applications.

A Guide to Chemical Considerations for the Pre-Clinical Development of Oligonucleotides.

Oligonucleotide therapeutics, a pioneering category of modern medicinal drugs, are at the forefront of utilizing innate mechanisms to modulate gene expression. With 18 oligonucleotide-based FDA-approved medicines currently available for treating various clinical conditions, this field showcases an innovative potential yet to be fully explored. Factors such as purity, formulation, and endotoxin levels profoundly influence the efficacy and safety of these therapeutics. Therefore, a thorough understanding of the chemical factors essential for producing high-quality oligonucleotides for preclinical studies is crucial in their development for further clinical application. This paper serves as a concise guide to these chemical considerations, aiming to inspire and equip researchers with the necessary knowledge to advance in this exciting and innovative field.

Molecular Mechanism of P53 Peptide Permeation through Lipid Membranes from Solid-State NMR Spectroscopy and Molecular Dynamics Simulations.

Macrocyclic peptides show promise in targeting high-value therapeutically relevant binding sites due to their high affinity and specificity. However, their clinical application is often hindered by low membrane permeability, which limits their effectiveness against intracellular targets. Previous studies focused on peptide conformations in various solvents, leaving a gap in understanding their interactions with and translocation through lipid bilayers. Addressing this, our study explores the membrane interactions of stapled peptides, a subclass of macrocyclic peptides, using solid-state nuclear magnetic resonance (ssNMR) spectroscopy and molecular dynamics (MD) simulations. We conducted ssNMR measurements on ATSP-7041M, a prototypical stapled peptide, to understand its interaction with lipid membranes, leading to an MD-informed model for peptide membrane permeation. Our findings reveal that ATSP-7041M adopts a stable α-helical structure upon membrane binding, facilitated by a cation-π interaction between its phenylalanine side chain and the lipid headgroup. This interaction makes the membrane-bound state energetically favorable, facilitating membrane affinity and insertion. The bound peptide displayed asymmetric insertion depths, with the C-terminus penetrating deeper (approximately 9 Å) than the N-terminus (approximately 4.3 Å) relative to the lipid headgroups. Contrary to expectations, peptide dynamics was not hindered by membrane binding and exhibited rapid motions similar to cell-penetrating peptides. These dynamic interactions and peptide-lipid affinity appear to be crucial for membrane permeation. MD simulations indicated a thermodynamically stable transmembrane conformation of ATSP-7041M, reducing the energy barrier for translocation. Our study offers an in silico view of ATSP-7041M's translocation from the extracellular to the intracellular region, highlighting the significance of peptide-lipid interactions and dynamics in enabling peptide transit through membranes.

Evaluating the role of large language models in inflammatory bowel disease patient information

This letter evaluates the article by Gravina et al on ChatGPT’s potential in providing medical information for inflammatory bowel disease patients. While promising, it highlights the need for advanced techniques like reasoning + action and retrieval-augmented generation to improve accuracy and reliability. Emphasizing that simple question and answer testing is insufficient, it calls for more nuanced evaluation methods to truly gauge large language models’ capabilities in clinical applications.

Automated remote sleep monitoring needs uncertainty quantification.

Wearable electroencephalography devices emerge as a cost-effective and ergonomic alternative to gold-standard polysomnography, paving the way for better health monitoring and sleep disorder screening. Machine learning allows to automate sleep stage classification, but trust and reliability issues have hampered its adoption in clinical applications. Estimating uncertainty is a crucial factor in enhancing reliability by identifying regions of heightened and diminished confidence. In this study, we used an uncertainty-centred machine learning pipeline, U-PASS, to automate sleep staging in a challenging real-world dataset of single-channel electroencephalography and accelerometry collected with a wearable device from an elderly population. We were able to effectively limit the uncertainty of our machine learning model and to reliably inform clinical experts of which predictions were uncertain to improve the machine learning model's reliability. This increased the five-stage sleep-scoring accuracy of a state-of-the-art machine learning model from 63.9% to 71.2% on our dataset. Remarkably, the machine learning approach outperformed the human expert in interpreting these wearable data. Manual review by sleep specialists, without specific training for sleep staging on wearable electroencephalography, proved ineffective. The clinical utility of this automated remote monitoring system was also demonstrated, establishing a strong correlation between the predicted sleep parameters and the reference polysomnography parameters, and reproducing known correlations with the apnea-hypopnea index. In essence, this work presents a promising avenue to revolutionize remote patient care through the power of machine learning by the use of an automated data-processing pipeline enhanced with uncertainty estimation.

Construction and evaluation of liposomal drug delivery system for an ALK/HDACs dual-targeted inhibitor with sustained release and enhanced antitumor effect.

ALK/HDACs dual target inhibitor (PT-54) was a 2,4-pyrimidinediamine derivative synthesized based on the pharmacophore merged strategy that inhibits both anaplastic lymphoma kinase (ALK) and histone deacetylases (HDACs), which has demonstrated significant efficacy in treating multiple cancers. However, its poor solubility in water limited its clinical application. In this study, we prepared PT-54 liposomes (PT-54-LPs) by the membrane hydration method to overcome this defect. The encapsulation efficiency (EE) and particle size were used as evaluation indicators to explore the preparation conditions of PT-54-LPs. The morphology, particle size, EE, drug loading content (DLC), drug release properties, and stability of PT-54-LPs were further investigated. In vitro drug release studies showed that PT-54-LPs exhibited significant slow-release properties compared with free PT-54. PT-54-LPs also showed better tumor inhibitory effects than free PT-54 without significant adverse effects. These results suggested that PT-54-LPs displayed sustained drug release and significantly improved the tumor selectivity of PT-54. Thus, PT-54-LPs showed significant promise in enhancing anticancer efficiency.

Quality and Safety Considerations for Therapeutic Products Based on Extracellular Vesicles.

Extracellular vesicles (EVs) serve as an intrinsic system for delivering functional molecules within our body, playing significant roles in diverse physiological phenomena and diseases. Both native and engineered EVs are currently the subject of extensive research as promising therapeutics and drug delivery systems, primarily due to their remarkable attributes, such as targeting capabilities, biocompatibility, and low immunogenicity and mutagenicity. Nevertheless, their clinical application is still a long way off owing to multiple limitations. In this context, the Science Board of the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan has conducted a comprehensive assessment to identify the current issues related to the quality and safety of EV-based therapeutic products. Furthermore, we have presented several examples of the state-of-the-art methodologies employed in EV manufacturing, along with guidelines for critical processes, such as production, purification, characterization, quality evaluation and control, safety assessment, and clinical development and evaluation of EV-based therapeutics. These endeavors aim to facilitate the clinical application of EVs and pave the way for their transformative impact in healthcare.

The Translational Medicine of 2030: Bedside to Biosphere.

For over two decades, translational medicine has accelerated basic science discovery into clinical application using a bench-to-bedside framework. Given that climate change represents the single greatest health threat facing humanity, the authors propose extending this framework to now include bedside to the biosphere. Several potential opportunities in clinical operations, research, and advocacy using this framework are provided. In addition, we propose that technology assessment studies of diagnostic imaging measure planetary outcomes alongside patient outcomes.

Rhodiola and Salidroside Attenuate Oxidative Stress-Triggered H9c2 Cardiomyoblast Apoptosis Through IGF1R-Induced ERK1/2 Activation.

Oxidative stress is a pivotal factor in the pathogenesis of various cardiovascular diseases. Rhodiola, a traditional Chinese medicine, is recognized for its potent antioxidant properties. Salidroside, a phenylpropanoid glycoside derived from Rhodiola rosea, has shown remarkable antioxidant capabilities. This study aimed to elucidate the potential protective mechanisms of Rhodiola and salidroside against H2O2-induced cardiac apoptosis in H9c2 cardiomyoblast cells. H9c2 cells were exposed to H2O2 for 4 h, and subsequently treated with Rhodiola or salidroside for 24 h. Cell viability and apoptotic pathways were assessed. The involvement of insulin-like growth factor 1 receptor (IGF1R) and the activation of extracellular regulated protein kinases 1/2 (ERK1/2) were investigated. H2O2 (100 μM) exposure significantly induced cardiac apoptosis in H9c2 cells. However, treatment with Rhodiola (12.5, 25, and 50 μg/mL) and salidroside (0.1, 1, and 10 nM) effectively attenuated H2O2-induced cytotoxicity and apoptosis. This protective effect was associated with IGF1R-activated phosphorylation of ERK1/2, leading to the inhibition of Fas-dependent proteins, HIF-1α, Bax, and Bak expression in H9c2 cells. The images from hematoxylin and eosin staining and immunofluorescence assays also revealed the protective effects of Rhodiola and salidroside in H9c2 cells against oxidative damage. Our findings suggest that Rhodiola and salidroside possess antioxidative properties that mitigate H2O2-induced apoptosis in H9c2 cells. The protective mechanisms involve the activation of IGF1R and subsequent phosphorylation of ERK1/2. These results propose Rhodiola and salidroside as potential therapeutic agents for cardiomyocyte cytotoxicity and apoptosis induced by oxidative stress in heart diseases. Future studies may explore their clinical applications in cardiac health.

Thermoresponsive On-Demand Adhesion and Detachment of a Polyurethane-Urea Bioadhesive.

The development of bioadhesives with strong adhesion and on-demand adhesion-detachment behavior is still critically important and challenging for facilitating painless and damage-free removal in clinical applications. In this work, for the first time, we report the easy fabrication of novel polyurethane-urea (PUU)-based bioadhesives with thermoresponsive on-demand adhesion and detachment behavior. The PUU copolymer was synthesized by a simple copolymerization of low-molecular-weight, hydrophilic, and biocompatible poly(ethylene glycol), glyceryl monolaurate (GML, a special chain extender with a long side hydrophobic alkyl group), and isophorone diisocyanate (IPDI). Here, GML was expected to not only adjust the temperature-dependent adhesion behavior but also act as an internal plasticizer. By simple adjustment of the water content, the adhesion strength of the 15 wt % water-containing PUU film toward porcine skin is as high as 55 kPa with an adhesion energy of 128 J/m2 at 37 °C. The adhesion strength dramatically decreases to only 3 kPa at 10 °C, exhibiting switching efficiency as high as 0.95. Furthermore, the present PUU-based adhesive also shows good on-demand underwater adhesion and detachment with a cell viability close to 100%. We propose that biomaterial research fields, especially novel PUU/polyurethane (PU)-based functional materials and bioadhesives, could benefit from such a novel thermoresponsive copolymer with outstanding mechanical and functional performances and an easy synthesis and scaled-up process as described in this article.

The current therapeutic cancer vaccines landscape in non-small cell lung cancer.

Currently, conventional immunotherapies for the treatment of non-small cell lung cancer (NSCLC) have low response rates and benefit only a minority of patients, particularly those with advanced disease, so novel therapeutic strategies are urgent deeded. Therapeutic cancer vaccines, a form of active immunotherapy, harness potential to activate the adaptive immune system against tumor cells via antigen cross-presentation. Cancer vaccines can establish enduring immune memory and guard against recurrences. Vaccine-induced tumor cell death prompts antigen epitope spreading, activating functional T cells and thereby sustaining a cancer-immunity cycle. The success of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rendered cancer vaccines a promising avenue, especially when combined with immunotherapy or chemoradiotherapy for NSCLC. This review delves into the intricate antitumor immune mechanisms underlying therapeutic cancer vaccines, enumerates the tumor antigen spectrum of NSCLC, discusses different cancer vaccines progress and summarizes relevant clinical trials. Additionally, we analyze the combination strategies, current limitations, and future prospects of cancer vaccines in NSCLC treatment, aiming to offer fresh insights for their clinical application in managing NSCLC. Overall, cancer vaccines offer promising potential for NSCLC treatment, particularly combining with chemoradiotherapy or immunotherapy could further improve survival in advanced patients. Exploring inhaled vaccines or prophylactic vaccines represents a crucial research avenue.