Progress In Clinical Application Research Articles

Standardisation is the key to the sustained, rapid and healthy development of stem cell-based therapy.

Stem cell-based therapy (SCT) is an important component of regenerative therapy that brings hope to many patients. After decades of development, SCT has made significant progress in the research of various diseases, and the market size has also expanded significantly. The transition of SCT from small-scale, customized experiments to routine clinical practice requires the assistance of standards. Many countries and international organizations around the world have developed corresponding SCT standards, which have effectively promoted the further development of the SCT industry. We conducted a comprehensive literature review to introduce the clinical application progress of SCT and focus on the development status of SCT standardization. We first briefly introduced the types and characteristics of stem cells, and summarized the current clinical application and market development of SCT. Subsequently, we focused on the development status of SCT-related standards as of now from three levels: the International Organization for Standardization (ISO), important international organizations, and national organizations. Finally, we provided perspectives and conclusions on the significance and challenges of SCT standardization. Standardization plays an important role in the sustained, rapid and healthy development of SCT.

Protective mechanism and clinical application of SGLT2 inhibitors in patients with type 2 diabetes mellitus complicated with abnormal liver function

Type 2 diabetes (T2DM) patients with abnormal liver function will further aggravate the complexity of the disease and affect the quality of life of patients. Sodium-glucose cotransporter protein 2 (SGLT2) inhibitors are novel hypoglycemic agents that may produce hepatoprotective effects in patients with T2DM combined with hepatic function abnormalities by improving hyperglycemic toxicity, regulating lipid metabolism, decreasing visceral adiposity, anti-inflammatory, antioxidant and other possible mechanisms. However, the exact mechanism has not been clarified and further studies are still needed. In this article, we reviewed the possible mechanisms of hepatoprotective effects of SGLT2i on patients with T2DM combined with abnormal liver function and the progress of clinical application, in order to providing reference for the rational application of SGLT2i.

Development of Proteasome Inhibitors for Cancer Therapy

Review Development of Proteasome Inhibitors for Cancer Therapy Xu Chen † , Xuan Wu † , Linyan Li, and Xiaoming Zhu * State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR, 999078, China * Correspondence: xmzhu@must.edu.mo Received: 12 January 2024 Accepted: 19 February 2024 Published: 18 March 2024 Abstract: The ubiquitin proteasome system (UPS) is considered a crucial degradation machinery in cellular processes of protein quality control and homeostasis. Dysregulation of the UPS is closely associated with many diseases. The proteasome is a key core component of the UPS, which can prevent the accumulation of misfolded proteins and regulate various cellular processes such as cell cycle, apoptosis, and immune responses. In the past two decades, a total of three proteasome inhibitors have been approved for the treatment of hematological malignancies, including bortezomib, carfilzomib, and ixazomib. Additionally, accumulating reports have suggested that some natural product-derived proteasome inhibitors have been developed as anti-cancer drug candidates. In this review, we summarize the development of proteasome inhibitors as well as the mechanisms involved, clinical application progress, and drug resistance. The natural products of proteasome inhibitors and their future perspectives will also be discussed.

Thiourea‐Cation Chelation Based Hydrogel and its Application as Antibacterial Dressing for the Repair of Diabetic Wound

AbstractFor various chronic wounds, bacterial infection is one of the important reasons that hinder their healing. Ion‐crosslinked antibacterial hydrogel dressings based on Ag+, Cu2+ and Zn2+, have made progress in clinical application. However, the toxicity of released metal ions cannot be ignored. Therefore, how to ensure the antibacterial performance of hydrogel dressing while reducing the amount of metal ions is a major challenge for the fabrication of metal ion based antibacterial hydrogel. In this study, a general method is proposed to design cationic ion‐crosslinked hydrogel based on thiourea groups. Taking the hydrogel formed by mixing thiourea modified hyaluronic acid (H‐ANCSN) with Ag+ (HA‐NCSN/Ag+ hydrogel) as an example, the characteristics and application potential of this kind of hydrogel are thoroughly explored. Due to the strong cationic chelation characteristics of thiourea groups, HA‐NCSN/Ag+ hydrogel can gel at low Ag+ concentration and achieve long‐term slow release of Ag+ at stable concentration to balance the antibacterial and biocompatible properties. Moreover, this dynamic thiourea‐Ag+ crosslinking also endowed the hydrogel with the property of “gelation and encapsulation first, injection to cover wound when necessary”. Then, the mangiferin self‐assembled nanoparticles are loaded into HA‐NCSN/Ag+ hydrogel as the radical oxygen species scavenger.

Landscape of adenosine pathway and immune checkpoint dual blockade in NSCLC: progress in basic research and clinical application.

Lung cancer poses a global threat to human health, while common cancer treatments (chemotherapy and targeted therapies) have limited efficacy. Immunotherapy offers hope of sustained remission for many patients with lung cancer, but a significant proportion of patients fail to respond to treatment owing to immune resistance. There is extensive evidence to suggest the immunosuppressive microenvironment as the cause of this treatment failure. Numerous studies have suggested that the adenosine (ADO) pathway plays an important role in the formation of an immunosuppressive microenvironment and may be a key factor in the development of immune resistance in EGFR-mutant cell lung cancer. Inhibition of this pathway may therefore be a potential target to achieve effective reversal of ADO pathway-mediated immune resistance. Recently, an increasing number of clinical trials have begun to address the broad prospects of using the ADO pathway as an immunotherapeutic strategy. However, few researchers have summarized the theoretical basis and clinical rationale of the ADO pathway and immune checkpoint dual blockade in a systematic and detailed manner, particularly in lung cancer. As such, a timely review of the potential value of the ADO pathway in combination with immunotherapy strategies for lung cancer is warranted. This comprehensive review first describes the role of ADO in the formation of a lung tumor-induced immunosuppressive microenvironment, discusses the key mechanisms of ADO inhibitors in reversing lung immunosuppression, and highlights recent evidence from preclinical and clinical studies of ADO inhibitors combined with immune checkpoint blockers to improve the lung cancer immunosuppressive microenvironment.

The Effects of Structural & Materials Design on the Mechanisms of Tissue Integration with the 3D Printed Polyether-Ether-Ketone Cranial Implants in Vivo

3D printed polyether-ether-ketone (PEEK) implant has become a popular clinical alternative to implants made of titanium alloy for cranial bone substitutes due to its bone-match properties, however its biological inert hindered the progress of clinical applications of such material. To enhance the tissue integration capability of PEEK implants and promote their long-term stability, cranial implants of gradient porous structures were designed and manufactured via fused filament fabrication (FFF) 3D printing technology in both PEEK and PEEK/HA composites materials, then functionally evaluation of the implants on the tissue in-growth and the osteointegration mechanisms was conducted via animal tests. The 3D printed PEEK scaffold was found to have 2–5 folds of the compressive strength to those of the natural cranial bone. The in vivo studies verified that the porous PEEK/HA scaffold could effectively induce the bone ingrowth to form a stable biointegration boundary surrounding the host bone tissue after 4 weeks of implantation. Moreover, the PEEK/HA scaffold showed no significant advantages in improving the soft tissue in-growth, only making its distribution more evenly. It is also interestingly to find out that the vertically connective pores throughout the implant did not enhance the tissue binding force even though it did promote the nutrient transportation. In conclusion, the use of PEEK/HA composite material and a well-designed porous structure was proved to be an effective approach to improve the biointegration between the implant and host tissues.

Reviewing the evolutive ACQ-to-AIE transformation of photosensitizers for phototheranostics.

Photodynamic therapy (PDT) represents an emerging noninvasive treatment technique for cancers and various nonmalignant diseases, including infections. During the process of PDT, the physical and chemical properties of photosensitizers (PSs) critically determine the effectiveness of PDT. Traditional PSs have made great progress in clinical applications. One of the challenges is that traditional PSs suffer from aggregation-caused quenching (ACQ) due to their discotic structures. Recently, aggregation-induced emission PSs (AIE-PSs) with a twisted propeller-shaped conformation have been widely concerned because of high reactive oxygen species (ROS) generation efficiency, strong fluorescence efficiency, and resistance to photobleaching. However, AIE-PSs also have some disadvantages, such as short absorption wavelengths and insufficient molar absorption coefficient. When the advantages and disadvantages of AIE-PSs and ACQ-PSs are complementary, combining ACQ-PSs and AIE-PSs is a "win-to-win" strategy. As far as we know, the conversion of traditional representative ACQ-PSs to AIE-PSs for phototheranostics has not been reviewed. In the review, we summarize the recent progress on the ACQ-to-AIE transformation of PSs and the strategies to achieve desirable theranostic applications. The review would be helpful to design more efficient ACQ-AIE-PSs in the future and to accelerate the development and clinical application of PDT.

Characterization of the Chemical Constituents in Radix gentianae by Ultra-High Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry.

Radix gentianae (RG) is a traditional Chinese medicine used for the treatment of acute and chronic hepatitis in clinic. However, the chemical profile of RG is still unconfirmed, which hindered the progress of pharmacological study and clinical application. In this study, ultra-high performance liquid chromatography together with quadrupole time-of-flight mass spectrometry techniques were employed to separate and characterize the chemical constituents in RG. Under the optimized conditions, a total of 60 compounds were rapidly identified or tentatively characterized. Results indicated that iridoid glucosides, flavonoids, organic acids, amino acids, saccharides and nucleosides were major constituents in RG. It is concluded the established method can help to clarify the substance basis and provide useful information for ascertaining the bioactive constituents and action mechanism of RG.

Classification of cancer cells at the sub-cellular level by phonon microscopy using deep learning

There is a consensus about the strong correlation between the elasticity of cells and tissue and their normal, dysplastic, and cancerous states. However, developments in cell mechanics have not seen significant progress in clinical applications. In this work, we explore the possibility of using phonon acoustics for this purpose. We used phonon microscopy to obtain a measure of the elastic properties between cancerous and normal breast cells. Utilising the raw time-resolved phonon-derived data (300 k individual inputs), we employed a deep learning technique to differentiate between MDA-MB-231 and MCF10a cell lines. We achieved a 93% accuracy using a single phonon measurement in a volume of approximately 2.5 μm3. We also investigated means for classification based on a physical model that suggest the presence of unidentified mechanical markers. We have successfully created a compact sensor design as a proof of principle, demonstrating its compatibility for use with needles and endoscopes, opening up exciting possibilities for future applications.

Advances in the preclinical and clinical research of proteolysis targeting chimera

Proteolysis targeting chimera (PROTAC) refers to heterobifunctional small molecules that can simultaneously bind an E3 ubiquitin ligase and a target protein, enabling specific degradation of the target protein with the aid of the ubiquitin proteasome system. At present, most PROTAC drugs are in the clinical trial stage, and the ligands are mainly non-covalent compounds. PROTAC drugs have the advantage of overcoming drug resistance and degrading "undruggable" target proteins, but non-covalent ligands could lead to the hook effect that undermines drug efficacy. With its own advantages, covalent ligands can avoid the occurrence of this phenomenon, which is of great help to the development of PROTAC. This review summarizes the progress in preclinical and clinical research and application of PROTAC molecules targeting three different classes of protein targets, including intranuclear, transmembrane, and cytosolic proteins. We also offer perspective discussions to provide research ideas and references for the future development of PROTAC.

Research progress in clinical application and pharmacological effect of Yiyi Fuzi Baijiang Powder

Yiyi Fuzi Baijiang Powder(YFBP), originating from Synopsis of the Golden Chamber, is a classic prescription composed of Coicis Semen, Aconiti Lateralis Radix Praeparata, and Patriniae Herba for the treatment of abscesses and pus discharge. This article presented a systematic analysis of the clinical application of YFBP, including the indicated diseases, the number of cases, efficacy, dosage, administration methods, and compatibility with other drugs. The analysis reveals that YFBP has a wide range of clinical applications. It is commonly used, often with modifications or in combination with western medicine, for diseases in the fields of gastroente-rology, gynecology, urology, dermatology, and others. And most of the Traditional Chinese Medicine(TCM) evidence involved in these diseases are damp-heat evudence. The prescription shows rich variations in clinical administration methods, and most of which are the treatment of aqueous decoction of it. The therapeutic effect is also significant, and the total effective rate of clinical treatment is re-latively high. Additionally, this article summarized the pharmacological research on YFBP and found that it possessed various pharmacological effects, including anti-inflammatory, antioxidant, anticancer, and immune-modulating properties. Finally, correlation analysis was conducted on the main diseases, TCM types, prescription doses, pharmacological effects and action targets of YFBP, which to show the relationship between these five aspects in a visual form, reflecting the relationship between its clinical application and modern pharmacological effects. These findings provide a reference basis for further development and research on YFBP.

Nuclear medicine radiomics in digestive system tumors: Concept, applications, challenges, and future perspectives.

Radiomics aims to develop novel biomarkers and provide relevant deeper subvisual information about pathology, immunophenotype, and tumor microenvironment. It uses automated or semiautomated quantitative analysis of high-dimensional images to improve characterization, diagnosis, and prognosis. Recent years have seen a rapid increase in radiomics applications in nuclear medicine, leading to some promising research results in digestive system oncology, which have been driven by big data analysis and the development of artificial intelligence. Although radiomics advances one step further toward the non-invasive precision medical analysis, it is still a step away from clinical application and faces many challenges. This review article summarizes the available literature on digestive system tumors regarding radiomics in nuclear medicine. First, we describe the workflow and steps involved in radiomics analysis. Subsequently, we discuss the progress in clinical application regarding the utilization of radiomics for distinguishing between various diseases and evaluating their prognosis, and demonstrate how radiomics advances this field. Finally, we offer our viewpoint on how the field can progress by addressing the challenges facing clinical implementation.

Twelve Years of Genome-Wide Association Studies of Human Protein N-Glycosylation

Most human-secreted and membrane-bound proteins have covalently attached oligosaccharide chains or glycans. Glycosylation influences the physical and chemical properties of proteins, as well as their biological functions. Unsurprisingly, alterations in protein glycosylation have been implicated in a growing number of human diseases, and glycans are increasingly being considered as potential therapeutic targets, an essential part of therapeutics, and biomarkers. Although glycosylation pathways are biochemically well-studied, little is known about the networks of genes that guide the cell- and tissue-specific regulation of these biochemical reactions in humans in vivo. The lack of a detailed understanding of the mechanisms regulating glycome variation and linking the glycome to human health and disease is slowing progress in clinical applications of human glycobiology. Two of the tools that can provide much sought-after knowledge of human in vivo glycobiology are human genetics and genomics, which offer a powerful data-driven agnostic approach for dissecting the biology of complex traits. This review summarizes the current state of human populational glycogenomics. In Section 1, we provide a brief overview of the N-glycan’s structural organization, and in Section 2, we give a description of the major blood plasma glycoproteins. Next, in Section 3, we summarize, systemize, and generalize the results from current N-glycosylation genome-wide association studies (GWASs) that provide novel knowledge of the genetic regulation of the populational variation of glycosylation. Until now, such studies have been limited to an analysis of the human blood plasma N-glycome and the N-glycosylation of immunoglobulin G and transferrin. While these three glycomes make up a rather limited set compared with the enormous multitude of glycomes of different tissues and glycoproteins, the study of these three does allow for powerful analysis and generalization. Finally, in Section 4, we turn to genes in the established loci, paying particular attention to genes with strong support in Section 5. At the end of the review, in Sections 6 and 7, we describe special cases of interest in light of new discoveries, focusing on possible mechanisms of action and biological targets of genetic variation that have been implicated in human protein N-glycosylation.

Human Mesenchymal Stem Cells and Innovative Scaffolds for Bone Tissue Engineering Applications.

Stem cell-based therapy is a significant topic in regenerative medicine, with a predominant role being played by human mesenchymal stem cells (hMSCs). The hMSCs have been shown to be suitable in regenerative medicine for the treatment of bone tissue. In the last few years, the average lifespan of our population has gradually increased. The need of biocompatible materials, which exhibit high performances, such as efficiency in bone regeneration, has been highlighted by aging. Current studies emphasize the benefit of using biomimetic biomaterials, also known as scaffolds, for bone grafts to speed up bone repair at the fracture site. For the healing of injured bone and bone regeneration, regenerative medicine techniques utilizing a combination of these biomaterials, together with cells and bioactive substances, have drawn a great interest. Cell therapy, based on the use of hMSCs, alongside materials for the healing of damaged bone, has obtained promising results. In this work, several aspects of cell biology, tissue engineering, and biomaterials applied to bone healing/regrowth will be considered. In addition, the role of hMSCs in these fields and recent progress in clinical applications are discussed. Impact Statement The restoration of large bone defects is both a challenging clinical issue and a socioeconomic problem on a global scale. Different therapeutic approaches have been proposed for human mesenchymal stem cells (hMSCs), considering their paracrine effect and potential differentiation into osteoblasts. However, different limitations are still to be overcome in using hMSCs as a therapeutic opportunity in bone fracture repair, including hMSC administration methods. To identify a suitable hMSC delivery system, new strategies have been proposed using innovative biomaterials. This review provides an update of the literature on hMSC/scaffold clinical applications for the management of bone fractures.

An overview and update of CO2 laser‑assisted sclerectomy surgery in primary open angle glaucoma (Review).

Glaucoma is the second leading cause of blindness worldwide. The proportion of cases of primary open-angle glaucoma (POAG) in China is gradually increasing. Glaucoma surgery has become more effective, safer, minimally invasive and personalized over the years. CO2 laser-assisted sclerectomy surgery (CLASS) is a minimally invasive glaucoma treatment. CLASS has recently been used to gradually lower intraocular pressure (IOP) in patients with POAG, pseudocapsular detachment syndrome and secondary glaucoma. In this operation, precise ablation of dry tissue followed by photocoagulation and effective absorption of water and percolating aqueous humor using CO2 laser are performed, and the IOP is lowered by the laser ablation of the deep sclera and the outer wall of the Schlemm's canal, facilitating the drainage of the aqueous humor. Compared with other filtering surgeries, CLASS has a shorter learning curve, lower technical difficulty and higher safety. The present study reviews the clinical application progress, safety and effectiveness of CLASS.

Bacteria derived extracellular vesicles in the pathogenesis and treatment of gastrointestinal tumours.

Extracellular vesicles are fundamentally significant in the communication between cells. Outer Membrane Vesicles(OMVs) are a special kind of EVs produced by Gram-negative bacteria, which are minute exosome-like particles budding from the outer membrane, which have been found to play essential roles in diverse bacterial life events, including regulation of microbial interactions, pathogenesis promotion, stress responses and biofilm formation. Recently, and more researches have explored the substantial potentials of EVs as natural functional nanoparticles in the bioengineering applications in infectious diseases, cardiovascular diseases, autoimmune diseases and neurological diseases, such as antibacterial therapy, cancer drugs and immunoadjuvants, with several candidates in clinical trials showing promising efficacy. However, due to the poor understanding of sources, membrane structures and biogenesis mechanisms of EVs, progress in clinical applications still remains timid. In this review, we summarize the latest findings of EVs, especially in gastrointestinal tract tumours, to provide a comprehensive introduction of EVs in tumorigenesis and therapeutics.

Cardiac Shock Wave Therapy in Cardiovascular Diseases

Cardiovascular disease is one of the leading causes of death worldwide, placing a huge burden on patients and healthcare systems. Cardiac shock wave (CSW) technology is a non-invasive treatment method. In recent years, some scholars have discovered that extracorporeal shock wave can improve cardiovascular ischemic lesions. This article reviews the latest progress in basic research and clinical application of cardiac shock wave technology in cardiovascular medicine and reviews its efficacy and potential mechanisms in different diseases. First, the principle of shock waves and their application potential in cardiovascular medicine are introduced. Then, from the aspects of basic research and clinical application, the mechanism and clinical efficacy of shock waves in cardiovascular diseases such as coronary heart disease, myocardial ischemia-reperfusion injury, atrial fibrillation, atherosclerosis, and coronary artery calcification are discussed, as well as its advantages and limitations. Animal experiments and clinical studies have found that low-energy extracorporeal shock waves can upregulate the expression of vascular endothelial growth factors, promote angiogenesis, promote nitric oxide production, increase local blood perfusion, significantly reduce angina symptoms, and improve left ventricular function and remodeling. Finally, the future development trend of shock wave technology is prospected. This review provides an introduction to the properties, biomechanical effects, treatment mechanisms of cardiovascular diseases, research status and development prospects of extracorporeal shock waves. Keywords: Cardiac shock Wave Therapy, Cardiovascular diseases, ESWT

Research progress on prostate-specific membrane antigen ligand positron emission tomography imaging of prostate cancer

Prostate cancer is the most common malignant tumor in male urinary system, and the morbidity and mortality rate are increasing year by year. Traditional imaging examinations have some limitations in the diagnosis of prostate cancer, and the advent of molecular imaging probes and imaging technology have provided new ideas for the integration of diagnosis and treatment of prostate cancer. In recent years, prostate-specific membrane antigen (PSMA) has attracted much attention as a target for imaging and treatment of prostate cancer. PSMA ligand positron emission tomography (PET) has important reference value in the diagnosis, initial staging, detection of biochemical recurrence and metastasis, clinical decision-making guidance and efficacy evaluation of prostate cancer. This article briefly reviews the clinical research and application progress on PSMA ligand PET imaging in prostate cancer in recent years, so as to raise the efficiency of clinical applications.

Rapid identification, quantitation, and antioxidant activity evaluation of the components in Guanxin Shutong capsule with liquid chromatography and mass spectrometry

Guanxin Shutong capsule (GSC) is a traditional Chinese medicinal prescription used in the treatment of coronary heart disease (CHD) and angina pectoris in clinic. However, the chemical profile of GSC is still uncovered, which hindered the progress of pharmacological study and clinical application. Herein, high performance liquid chromatography (HPLC) together with high resolution mass spectrometry (HR-MS) techniques were employed to analyze the quality consistency and to identify chemical components in GSC. As a result, a total of 111 compounds were tentatively annotated. Quantitative analysis based on HPLC-ultraviolet detection (UV) was performed for 6 main components and fingerprints of 10 different batches of GSC were established. The developed method was validated for linearity, precision, repeatability, stability, and recovery. The quality evaluation and similarity analysis of the 10 batches were also performed. Furthermore, in vitro antioxidant activity assays demonstrated that GSC exhibited potential DPPH and hydroxyl radical scavenging capacities. Especially, salvianolic acids showed the strongest free radical scavenging capacities, which might be the main component for quality control of GSC.

Clinical application progress of subjective visual vertical test

Subjective visual vertical test is considered as an effective technique to evaluate otolith organ function and central pathway of gravity perception. This test is non-invasive, easy to operate and has little stimulation. At present, there are few such studies in China. This paper reviews the concept, measurement principle and method, influencing factors, application, advantages and disadvantages of subjective visual vertical test.