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The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy. Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells. Anti-tumor drugs were developed to induce apoptosis, but some patient’s show apoptosis escape and chemotherapy resistance. Therefore, other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment. Ferroptosis is a newly discovered iron-dependent, non-apoptotic type of cell death that is highly negatively correlated with cancer development. Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis. This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment.

BACKGROUND Enhanced recovery after surgery (ERAS) was introduced in China in 2007. Over time, the scope of ERAS has expanded from abdominal surgery to orthopedics, urology and other fields. Continuous development and research has contributed to progress of ERAS in China. In 2019, to promote the application of ERAS in bone tumor surgery, we formed the “Consensus of Experts on Perioperative Management of Accelerated Rehabilitation in Major Surgery of Bone Tumors in China”. AIM To evaluate the effect of enhanced recovery after bone tumor surgery in perioperative management in China. METHODS One hundred and seven patients who underwent bone tumor surgery at the Second Affiliated Hospital of Xi’an Jiaotong University between May 2019 and April 2021 were randomized into a study group (53 cases) and a control group (54 cases). The study group adopted the ERAS protocol and the control group adopted conventional care. Main outcome measures included postoperative length of stay (LOS), postoperative complications, mortality, and 30-d readmission rates. Secondary outcomes included postoperative visual analog scale (VAS) score of pain, number of blood transfusions, drainage volume in 24 h after operation, patient satisfaction 30 d after discharge, VAS score at 30 d after discharge, and daily standing walking time. RESULTS There were no significant differences in the baseline data, clinical features and surgical site between the two groups. The LOS in the study group with the ERAS protocol was 7.72 ± 3.34 d compared with 10.28 ± 4.27 d in the control group who followed conventional care. The incidence of postoperative nausea and vomiting (PONV) in the study group was 19% and 37% in the control group. The VAS scores of pain on postoperative day 1 (POD1) and POD3 in the study group were 4.79 ± 2.34 and 2.79 ± 1.53 compared with 5.28 ± 3.27 and 3.98 ± 2.27 in the control group. The drainage volume in 24 h after the operation was 124.36 ± 23.43 mL in the study group and 167.43 ± 30.87 mL in the control group. The number of blood transfusions in the study group was also lower. The patient satisfaction rate was higher in the study group than in the control group. CONCLUSION The ERAS protocol in the perioperative period of bone tumor surgery can decrease LOS, PONV, and postoperative pain, blood transfusion and 24-h drainage, improve patient satisfaction and accelerate recovery.

Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from mesoderm during early development that are characterized by high self-renewal ability and multidirectional differentiation potential. These cells are present various tissues in the human body and can be cultured in vitro. Under specific conditions, MSCs can differentiate into osteoblasts, neuron-like cells, adipocytes and muscle cells and so on, therefore, have a great application value in cell replacement therapy and tissue repair. In recent years, the application of MSCs in rheumatic diseases has received increasing attention. On the one hand, MSCs have the ability to differentiate into bone and cartilage cells; on the other hand, these stem cells are also involved in immune regulation, resulting in the alleviation of inflammation and anti-fibrotic properties and the promotion of vascular repair, thus bringing new hope for the treatment of rheumatic diseases. This article reviews the clinical progress in MSC application for the treatment of rheumatic diseases.

Vascular injury is a frequent pathology in coronary artery disease. To repair the vasculature, scientists have found that endothelial progenitor cells (EPCs) have excellent properties associated with angiogenesis. Over time, research on EPCs has made encouraging progress regardless of pathology or clinical technology. This review focuses on the origins and cell markers of EPCs, and the connection between EPCs and coronary artery disease. In addition, we summarized various studies of EPC-capturing stents and EPC infusion therapy, and aim to learn from past technology to predict the future.

Pancreatic cancer (PC) is an aggressive human cancer. Appropriate methods for the diagnosis and treatment of PC have not been found at the genetic level, thus making epigenetics a promising research path in studies of PC. Histone methylation is one of the most complicated types of epigenetic modifications and has proved crucial in the development of PC. Histone methylation is a reversible process regulated by readers, writers, and erasers. Some writers and erasers can be recognized as potential biomarkers and candidate therapeutic targets in PC because of their unusual expression in PC cells compared with normal pancreatic cells. Based on the impact that writers have on the development of PC, some inhibitors of writers have been developed. However, few inhibitors of erasers have been developed and put to clinical use. Meanwhile, there is not enough research on the reader domains. Therefore, the study of erasers and readers is still a promising area. This review focuses on the regulatory mechanism of histone methylation, and the diagnosis and chemotherapy of PC based on it. The future of epigenetic modification in PC research is also discussed.

The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria. As an excellent candidate to overcome antibiotic resistance, antimicrobial peptides (AMPs) that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity. These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action. This comprehensive review provides a broad overview of AMPs from the origin, structural characteristics, mechanisms of action, biological activities to clinical applications. We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics. Supplementary Information The online version contains supplementary material available at 10.1186/s40779-021-00343-2.

BACKGROUND Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix-associated protein. Studies have revealed that SPARC is involved in the cell interaction and function including proliferation, differentiation, and apoptosis. However, the role of SPARC in cancer is controversial, as it was reported as the promoter or suppressor in different cancers. Further, the role of SPARC in lymphoma is unclear. AIM To identify the expression and significance of SPARC in lymphoma, especially in diffuse large B-cell lymphoma (DLBCL). METHODS The expression analysis of SPARC in different cancers was evaluated with Oncomine. The Brune, Eckerle, Piccaluga, Basso, Compagno, Alizadeh, and Rosenwald datasets were included to evaluate the mRNA expression of SPARC in lymphoma. The Cancer Genome Atlas (TCGA)-DLBCL was used to analyze the diagnostic value of SPARC in DLBCL. The Compagno and Brune DLBCL datasets were used for validation. Then, the diagnostic value was evaluated with the receiver operating characteristic (ROC) curve. The Kaplan-Meier plot was conducted with TCGA-DLBCL, and the ROC analysis was performed based on the survival time. Further, the overall survival analysis based on the level of SPARC expression was performed with the GSE4475 and E-TABM-346. The Gene Set Enrichment Analyses (GSEA) was performed to make the underlying mechanism-regulatory networks. RESULTS The pan-cancer analysis of SPARC showed that SPARC was highly expressed in the brain and central nervous system, breast, colon, esophagus, stomach, head and neck, pancreas, and sarcoma, especially in lymphoma. The overexpression of SPARC in lymphoma, especially DLBCL, was confirmed in several datasets. The ROC analysis revealed that SPARC was a valuable diagnostic biomarker. More importantly, compared with DLBCL patients with low SPARC expression, those with higher SPARC expression represented a higher overall survival rate. The ROC analysis showed that SPARC was a favorable prognostic biomarker for DLBCL. Results of the GSEA confirmed that the high expression of SPARC was closely associated with focal adhesion, extracellular matrix receptor interaction, and leukocyte transendothelial migration, which suggested that SPARC may be involved in the regulation of epithelial-mesenchymal transition, KRAS, and myogenesis in DLBCL. CONCLUSION SPARC was highly expressed in DLBCL, and the overexpression of SPARC showed sound diagnostic value. More interestingly, the overexpression of SPARC might be a favorable prognostic biomarker for DLBCL, suggesting that SPARC might be an inducible factor in the development of DLBCL, and inducible SPARC was negative in some oncogenic pathways. All the evidence suggested that inducible SPARC might be a good diagnostic and prognostic biomarker for DLBCL.

Introduction: Nasopharyngeal carcinoma (NPC) is an endemic malignancy in Southeast Asia, particularly Southern China. The classical non-keratinising cell type is almost unanimously associated with latent Epstein-Barr virus (EBV) infection. Circulating plasma EBV DNA can be a useful biomarker in various clinical aspects, but comprehensive recommendations and international guidelines are still lacking. We conducted a systematic review of all original articles on the clinical application of plasma EBV DNA for NPC; we further evaluated its strengths and limitations for consideration as standard recommendations. Methods: The search terms 'nasopharyngeal OR nasopharynx', and 'plasma EBV DNA OR cell-free EBV OR cfEBV' were used to identify full-length articles published up to December 2020 in the English literature. Three authors independently reviewed the article titles, removed duplicates and reviewed the remaining articles for eligibility. Results: A total of 81 articles met the eligibility criteria. Based on the levels of evidence and grades of recommendation assessed, it is worth considering the inclusion of plasma EBV DNA in screening, pre-treatment work-up for enhancing prognostication and tailoring of treatment strategy, monitoring during radical treatment, post-treatment surveillance for early detection of relapse, and monitoring during salvage treatment for recurrent or metastatic NPC. One major limitation is the methodology of measurement requiring harmonisation for consistent comparability. Conclusions: The current comprehensive review supports the inclusion of plasma EBV DNA in international guidelines in the clinical aspects listed, but methodological issues must be resolved before global application. 2021 Elsevier Ltd. All rights reserved.

The simplicity of converting medicinal solutions and suspensions into aerosols using mechanical and thermal energy, convenient delivery to the airways allows nebulizers to take a worthy place in the treatment of hospitalized and outpatient patients. Different types of nebulizers are available for use in the home and in medical settings (jet, ultrasound, membrane), and researches show that the performance and characteristics of the aerosol vary between different devices and manufacturers. Jet nebulizers are still the most used devices that do not require coordination of inhale and delivery of aerosol to the respiratory tract. To reduce the consumption of medicinal aerosol and optimize the air flow, virtual valve technology (V.V.T.) is being improved, and breath-actuated nebulizers are being created. The advantage of nebulizer therapy is the ability to apply large doses of medications, use substances that exist only in inhaled form. The choice falls on the nebulizer in cases where the patient can not use other delivery devices, for example, if the patient is unable to coordinate the inhalation and intake of the drug into the respiratory tract, with a severe exacerbation of obstructive disease, in the presence of motor disorders. The optimal delivery device for children of any age, including newborns, is a nebulizer. The most common indication for nebulizer therapy is the delivery of bronchodilators and inhaled corticosteroids for asthma or chronic obstructive pulmonary disease, as well as the treatment of upper respiratory tract diseases, in particular croup in children. An important place is given to nebulizers when it is necessary to prescribe certain mucolytics and antibiotics. In the treatment of emergency conditions, inhalation administration of drugs may be required, including situations when the patient is on mechanical ventilation or has a tracheostomy installed. The significance of nebulizers in the treatment of cystic fibrosis, pulmonary arterial hypertension, and alpha-1-antitrypsin deficiency is being studied. The possibilities of endobronchial delivery of heparin, insulin, and monoclonal antibodies are evaluated.

Background Liver transplantation is the only curative treatment option for end-stage liver disease; however, its use remains limited due to a shortage of suitable organs. In recent years, ex vivo liver machine perfusion has been introduced to liver transplantation, as a means to expand the donor organ pool. Purpose To present a systematic review of prospective clinical studies on ex vivo liver machine perfusion, in order to assess current applications and highlight future directions. Methods A systematic literature search of both PubMed and ISI web of science databases as well as the ClinicalTrials.gov registry was performed. Results Twenty-one articles on prospective clinical trials on ex vivo liver machine perfusion were identified. Out of these, eight reported on hypothermic, eleven on normothermic, and two on sequential perfusion. These trials have demonstrated the safety and feasibility of ex vivo liver machine perfusion in both standard and expanded criteria donors. Currently, there are twelve studies enrolled in the clinicaltrials.gov registry, and these focus on use of ex vivo perfusion in extended criteria donors and declined organs. Conclusion Ex vivo liver machine perfusion seems to be a suitable strategy to expand the donor pool for liver transplantation and holds promise as a platform for reconditioning diseased organs.

Purpose This study aims to evaluate the best possible practice using hybrid volumetric modulated arc therapy (H-VMAT) for hypofractionated radiation therapy of breast cancer. Different combinations of H‑VMAT—a combination of three-dimensional radiotherapy (3D-CRT) and VMAT—were analyzed regarding planning target volume (PTV), dose coverage, and exposure to organs at risk (OAR). Methods Planning computed tomography scans were acquired in deep-inspiration breath-hold. A total of 520 treatment plans were calculated and evaluated for 40 patients, comprising six different H‑VMAT plans and a 3D-CRT plan as reference. H‑VMAT plans consisted of two treatment plans including 3D-CRT and VMAT. During H‑VMAT planning, the use of hard wedge filters (HWF) and beam energies were varied. The reference plans were planned with mixed beam energies and the inclusion/omission of HWF. Results Compared to the reference treatment plans, all H‑VMAT plans showed consistently better PTV dose coverage, conformity, and homogeneity. Additionally, OAR protection was significantly improved with several H‑VMAT combinations (p Conclusion The H‑VMAT technique is an effective possibility for generating homogenous and conformal dose distributions. With the right choice of H‑VMAT combination, superior OAR protection is achieved compared to 3D-CRT.

Antibody drug conjugates (ADCs) normally compose of a humanized antibody and small molecular drug via a chemical linker. After decades of preclinical and clinical studies, a series of ADCs have been widely used for treating specific tumor types in the clinic such as brentuximab vedotin (Adcetris®) for relapsed Hodgkin's lymphoma and systemic anaplastic large cell lymphoma, gemtuzumab ozogamicin (Mylotarg®) for acute myeloid leukemia, ado-trastuzumab emtansine (Kadcyla®) for HER2-positive metastatic breast cancer, inotuzumab ozogamicin (Besponsa®) and most recently polatuzumab vedotin-piiq (Polivy®) for B cell malignancies. More than eighty ADCs have been investigated in different clinical stages from approximately six hundred clinical trials to date. This review summarizes the key elements of ADCs and highlights recent advances of ADCs, as well as important lessons learned from clinical data, and future directions., Graphical abstract Antibody drug conjugates (ADCs), normally composed of a humanized antibody and small molecular drugs via chemical linkers, represent a rapidly growing field for cancer therapy. In this review, we provide an overview of ADCs in preclinical and clinical development, as well as future directions of ADCs.Image 1

The rapid development of metagenomics, metabolomics, and metatranscriptomics provides novel insights into the intestinal microbiota factors linked to inflammatory bowel disease (IBD). Multiple microorganisms play a role in intestinal health; these include bacteria, fungi, and viruses that exist in a dynamic balance to maintain mucosal homeostasis. Perturbations in the intestinal microbiota disrupt mucosal homeostasis and are closely related to IBD in humans and colitis in mice. Therefore, preventing or correcting the imbalance of microbiota may serve as a novel prevention or treatment strategy for IBD. We review the most recent evidence for direct or indirect interventions targeting intestinal microbiota for treatment of IBD in order to overcome the current limitations of IBD therapies and shed light on personalized treatment options.

The authors on the basis of analytical review of the world literature analyzed the pharmacological activity of melatonin in the aspect of clinical use in COVID-19. Melatonin is traditionally considered a hormone of the pineal gland, which provides the interaction of organism with environment for information about the light regime of the environment. Until recently, the main scope of this drug was various sleep disorders. However, subsequent studies revealed that the melatonin’s ability to exert anticonvulsant, antidepressant, antineoplastic, neuroprotective, antioxidant and anti-gonadotropic effect and have some therapeutic activity for pharmacotherapy of tinnitus, migraine, neurodegenerative diseases, epilepsy, breast cancer, diseases of the respiratory and cardiovascular systems. The article found that a valuable effect of melatonin is its ability to reduce the release of proinflammatory cytokines, thereby reducing the intensity of inflammation and «cytokine storm» in patients with COVID-19. The paper notes that melatonin’s role as antioxidant, reduce the risk of oxidative stress during inflammation, but also as a factor of prevention of the development of «cytokine storm», with the development of which is associated with high risks of mortality at COVID-19. Melatonin is effective in patients hospitalized with COVID-19 by reducing vascular permeability, levels of General anxiety, use of sedatives and improve sleep quality. Found that melatonin can be used in combination with drugs and therapies COVID-19. For example, melatonin and alpha-lipoic acid may decrease kidney damage from oxidative stress caused by a combination of antiviral medications lopinavir/ritonavir. Using melatonin to mitigate medical and social problems in the context of a global pandemic may be substantial and socially responsible measure to preserve and maintain the health of the population. The authors found that the pharmacological activity of melatonin in the aspect of clinical use in COVID-19 is associated with its antioxidant and anti-stress activity that can be used effectively in conditions of coronavirus infection.

Background Nowadays, the latent power of technology, which can offer innovative resolutions to disease diagnosis, has awakened high-level anticipation in the community of patients as well as professionals. An easy-to-use mobile app is developed by us, which is purposefully intended for those patients with glaucoma. Methods A mobile App has been invented for smartphones for the convenient use wherever and whenever. The corresponding experiments carried out by public retinal image database and real captured clinical data reveal the ideal classification accuracy of the App. Also, user feedback evaluation is also carried out in terms of performance test as well as and users’ experience. Results For clinical test using Yanbao App, we found 274 patients for the identification with 648 retinal images to be evaluated by glaucoma classification. Of the 243 glaucoma patients, 191 were screened out with an accuracy of 0.7860 (sensitivity); the number of non-glaucoma patients was 310 of 405, and the accuracy reached 0.7654 (specificity).` The total Accuracy amounted to 0.7731, and the result is close to the test performance obtained on public dataset ORIGA and DRISHTI-GS1. Conclusions Yanbao App can be applied as an innovative approach exploiting mobile technology to enhance the clinicians’ efficiency and a balanced medical resources as well as a provided better tiered medical service system.

The neuronavigation system is a combination of navigation technology and neurosurgery. It can be used to assist in neurosurgery through three-dimensional reconstruction of medical image data, extraction of lesions, optimal surgical path planning, tracking and positioning of surgical instruments, and real-time intraoperative display. Accurate and maximal treatment of lesions, while effectively avoiding secondary injuries to patients during surgery. Therefore, the development and application of neuronavigation systems are reviewed.

Computer vision based patient activity monitoring systems can be attractive for various unobtrusive clinical applications. Such a monitoring system can be developed using movement information derived from the skeleton model of the current body pose, e.g. obtained using a depth camera. Earlier research using estimated skeleton models have been focused mostly on gaming applications. In this paper, we propose CNN-SkelPose as a skeleton model estimation method for clinical applications. CNN-SkelPose uses a trained Convolutional Neural Network to extract both the local and global information from the depth image. CNN-SkelPose outperforms the baseline model of Skeltrack for reliable skeleton model estimation in patient monitoring scenarios. Our results show the inadequacy of existing methods for skeleton model estimation when applied to a clinical scenario and suggests CNN-SkelPose as an improvement towards this application.

The glycoprotein stanniocalcin‐1 functions as a regulatory endocrine hormone that maintains the balance of calcium and phosphorus in bony fish and as a paracrine/autocrine factor involved in many physiological/pathological processes in humans, including carcinogenesis. In this review, we provide an overview of (a) the possible mechanisms through which STC1 affects the malignant properties of cancer, (b) transcriptional and post‐transcriptional regulation pathways of STC1 and (c) the potential clinical relevance of STC1 as a cancer biomarker and even a therapeutic target in the future. Exploring the role of STC1 in cancer development may provide a better understanding of the tumorigenesis process in humans and may facilitate finding an effective therapeutic method against cancer.

Antibiotic resistance represents a key challenge of the 21st century. Since the pipeline of new antibiotics in development is limited, the introduction of alternative antimicrobial strategies is urgently required. Bacteriophage therapy, the use of bacterial viruses to selectively kill bacterial pathogens, is re-emerging as a potential strategy to tackle difficult-to-treat and multidrug-resistant pathogens. The last decade has seen a surge in scientific investigation into bacteriophage therapy, including targeting orthopaedic-device-related infections (ODRIs) in several successful case studies. However, pharmacological data, knowledge on the interplay with the immune system and, especially in ODRIs, the optimal local application strategy and treatment outcomes remain scarce. The present review reports the state-of-the-art in bacteriophage therapy in ODRIs and addresses the hurdles in establishing bacteriophage therapy under good clinical practice guidelines. These hurdles include a lack of data concerning bacteriophage production, processing, administration and dosing, as well as follow-up clinical monitoring reports. To overcome these challenges, an integrated clinical approach is required, supported by comprehensive legislature to enable expansive and correctly implemented clinical trials. ispartof: EUROPEAN CELLS & MATERIALS vol:39 pages:193-210 ispartof: location:Switzerland status: published

Background Patients with severe oligospermia and nonobstructive azoospermia have very limited numbers of viable sperm in their epididymal and testicular samples. Thus, cryopreservation of their sperm is performed to avoid repeated sperm retrievals and to preserve their sperm from any side effects of any treatment regimens. Main body The development of intracytoplasmic sperm injection technology has extended the therapeutic capacity of assisted reproductive technology for men with azoospermia via the surgical or percutaneous isolation of sperm from the testis/epididymis. The conventional cryopreservation techniques are inadequate for preserving individually selected sperm. The technique for freezing single sperm was first developed in 1997 and has been explored from the perspective of frozen carriers, freezing programs, and cryoprotectant formulations. Among these methods, advances in frozen carriers have directly improved single-sperm freezing technology. In this review, we evaluate the different technologies for the cryopreservation of single sperm by discussing the advantages and disadvantages of different freezing methods, their clinical applications, and the outcomes for a range of frozen carriers. Conclusion Our review article describes the latest and current technologies implemented for the cryopreservation of single sperm that could potentially benefit patients with severe oligospermia and who rarely have any sperm in their ejaculate. This review provides a platform to understand the process and pitfalls of single-sperm cryopreservation to ensure further improvements in the cryopreservation technology in future studies.

Patients with chronic kidney disease (CKD) have a greatly enhanced risk of cardiovascular morbidity and mortality. Over the past decade it has come clear that a disturbed calcium-phosphate metabolism, with Fibroblast Growth Factor-23 as a key hormone, is partly accountable for this enhanced risk. Numerous studies have been performed unravelling FGF23s actions and its association with clinical conditions. As FGF23 is strongly associated with adverse outcome it may be a promising biomarker for risk prediction or, even more important, targeting FGF23 may be a strategy to improve patient outcome. This review elaborates on the clinical usefulness of FGF23 measurement. Firstly it discusses the reliability of the FGF23 measurement. Secondly, it evaluates whether FGF23 measurement may lead to improved patient risk classification. Finally, and possibly most importantly, this review evaluates if lowering of FGF23 should be a target for therapy. For this, the review discusses the current evidence indicating that FGF23 may be in the causal pathway to cardiovascular pathology, provides an overview of strategies to lower FGF23 levels and discusses the current evidence concerning the benefit of lowering FGF23.

Cell-free DNA (cfDNA) has pioneered the development of noninvasive prenatal testing and liquid biopsy, its emerging applications include organ transplantation, autoimmune diseases, and many other disorders; size profile of cfDNA is a crucial biological property and is essential for its clinical applications. Therefore, a thorough mastery of the characteristic and potential applications of cfDNA size profile is needed. Methods: Based on the recent researches, we summarized the size profile of cfDNA in pregnant women, tumor patients, transplant recipients and systemic lupus erythematosus (SLE) patients to explore the common features. We also concluded the applications of size profile in pre-analytical phases, analytical phases for novel assays, and preparation of quality control materials (QCMs). Results: The size profile of cfDNA shared common features in different populations, and was distributed as a “ladder” pattern with a dominant peak at ~166 bp. However, cfDNA entailed slightly discrepant characteristics due to specific tissues of origin. The dominant peaks of fetal and maternal cfDNA fragments in pregnant women were at 143 bp and 166 bp, respectively. The plasma cfDNA in tumor patients, transplant recipients, and SLE patients had a peak of around 166 bp. In pre-analytical phases, size profile served as a vital indicator to judge the eligibility of specimens, thus ensuring the successful implementation of assays. More importantly, the size profile had the potential to enrich short fragments, calculate fetal fraction, detect fetal abnormalities, predict tumor progress in analytical phase and to guide the preparation of QCMs. Conclusions: Our finding summarized the characteristics and potential applications of cfDNA size profile, providing clinical researchers with novel assays by the extensive application of cfDNA.

For the past few decades, spinal cord injury (SCI) has been believed to be an incurable traumatic condition, but with recent developments in stem cell biology, the field of regenerative medicine has gained hopeful momentum in the development of a treatment for this challenging pathology. Among the treatment candidates, transplantation of neural precursor cells has gained remarkable attention as a reasonable therapeutic intervention to replace the damaged central nervous system cells and promote functional recovery. Here, we highlight transplantation therapy techniques using induced pluripotent stem cells to treat SCI and review the recent research giving consideration to future clinical applications., Highlights • Transplantation of iPSC-derived neural precursor cells (NPCs) shows beneficial effects for spinal cord injury (SCI). • Because unsafe iPSC-NPC lines can form tumors after grafting, provisions to attenuate this risk are substantially important. • Clinical application for SCI patients using iPSCs will be conducted in the near future.

Nasopharyngeal carcinoma (NPC) is a malignancy that arises from the mucosal epithelium of the nasopharynx, and its prognosis is relatively favorable. The 5-year overall survival rate in patients with locally advanced NPC currently exceeds 80%, but the development of individualized diagnosis and treatment at the molecular level is relatively lacking. Circulating tumor cells (CTCs) is the generic term for tumor cells that are present in the peripheral blood circulation. As a new biomarker with good clinical application prospects, the detection of CTCs has the advantages of being non-invasive, simple, and repeatable. By capturing and detecting CTCs in peripheral blood and monitoring the dynamic variation of its type and quantity, we can assess the biological characteristics of tumor in a timely manner and evaluate the therapeutic effect and prognosis of patients in advance, which will help to develop individualized treatments of tumors. The primary purposes of this review were the clinical application of CTCs in tumor stage determination, treatment efficacy evaluation, and prognosis prediction of NPC. In addition, we estimated the correlation between Epstein-Barr virus infection and CTCs and analyzed the difference in karyotypes and specific markers expressed on CTCs. We believe that our study will provide new insights and biomarkers for the individualized treatment of patients with NPC.

Advanced therapy medicinal products (ATMPs) offer new prospects to improve the treatment of conditions with unmet medical needs. Kidney diseases are a current major health concern with an increasing global prevalence. Chronic renal failure appears after many years of impairment, which opens a temporary window to apply novel therapeutic approaches to delay or halt disease progression. The immunomodulatory, anti-inflammatory, and pro-regenerative properties of mesenchymal stromal cells (MSCs) have sparked interest for their use in cell-based regenerative therapies. Currently, several early-phase clinical trials have been completed and many are ongoing to explore MSC safety and efficacy in a wide range of nephropathies. However, one of the current roadblocks to the clinical translation of MSC therapies relates to the lack of standardization and harmonization of MSC manufacturing protocols, which currently hinders inter-study comparability. Studies have shown that cell culture processing variables can have significant effects on MSC phenotype and functionality, and these are highly variable across laboratories. In addition, heterogeneity within MSC populations is another obstacle. Furthermore, MSCs may be isolated from several sources which adds another variable to the comparative assessment of outcomes. There is now a growing body of literature highlighting unique and distinctive properties of MSCs according to the tissue origin, and that characteristics such as donor, age, sex and underlying medical conditions may alter the therapeutic effect of MSCs. These variables must be taken into consideration when developing a cell therapy product. Having an optimal scale-up strategy for MSC manufacturing is critical for ensuring product quality while minimizing costs and time of production, as well as avoiding potential risks. Ideally, optimal scale-up strategies must be carefully considered and identified during the early stages of development, as making changes later in the bioprocess workflow will require re-optimization and validation, which may have a significant long-term impact on the cost of the therapy. This article provides a summary of important cell culture processing variables to consider in the scale-up of MSC manufacturing as well as giving a comprehensive review of tissue of origin-specific biological characteristics of MSCs and their use in current clinical trials in a range of renal pathologies.

Dengzhanxixin (DZXX), the dried whole plant of Erigeron breviscapus (Vaniot) Hand.-Mazz., belonging to Compositae and first published in Materia Medica of South Yunnan by Lan Mao in the Ming Dynasty (1368 AD–1644 AD), is included in Medicinal Materials and Decoction Pieces of the 2020 edition of the Pharmacopeia of the People’s Republic of China. Its main chemical components are flavonoids that mainly include flavonoid, flavonols, dihydroflavones, flavonol glycosides, flavonoid glycosides, coffee acyl compounds, and other substances, such as volatile oil compounds, coumarins, aromatic acids, pentacyclic terpenoids, phytosterols, and xanthones. Among them, scutellarin and 1,5-dicoffeoylquininic acid are the main active components of DZXX. DZXX has pharmacological effects, such as improving cerebral and cerebrovascular ischemia, increasing blood flow, inhibiting platelet aggregation, promoting antithrombotic formation, improving microcirculation, reducing blood viscosity, protecting optic nerves, exhibiting anti-inflammatory properties, scavenging free radicals, and eliciting antioxidant activities. It is widely used in the treatment of cardiovascular and cerebrovascular ischemic diseases, kidney diseases, liver diseases, diabetic complications, and glaucoma. Pharmacokinetic studies have shown that the active components of DZXX have a low bioavailability and a high elimination rate in vivo. Nevertheless, its utilization can be improved through liposome preparation and combination with other drugs. Acute and subacute toxicity studies have shown that DZXX is a safe medicinal material widely used in clinical settings. However, its target and drug action mechanism are unclear because of the complexity of its composition. In this paper, the clinical application and pharmacological toxicology of DZXX are reviewed to provide a reference for further studying its active components and action mechanism.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and a leading cause of cancer-related deaths. Due to late diagnosis, early intrahepatic metastasis and nonresponse to systemic treatments, surgical resection and/or biopsy specimens remain the gold standard for disease staging, grading and clinical decision-making. Since only a small amount of tissue was obtained in a needle biopsy, the conventional tissue biopsy is unable to represent tumor heterogeneity in HCC. For this reason, it is imperative to find a new non-invasive and easily available diagnostic tool to detect HCC at an early stage and to monitor HCC recurrence. The past decade has witnessed considerable evolution in the development of liquid biopsy technologies with the emergence of next-generation sequencing. As a liquid biopsy approach, molecular analysis of cell-free DNA (cfDNA), characterized by noninvasiveness and real-time analysis, may accurately represent the tumor burden and comprehensively reflect genetic profile of HCC. Therefore, cfDNA may be used clinically as a predictive biomarker in early diagnosis, outcome assessment, and even molecular typing. In this review, we provide an update on the recent advances made in clinical applications of cfDNA in HCC.

Photodynamic therapy (PDT) has been used as an anti-tumor treatment method for a long time and photosensitizers (PS) can be used in various types of tumors. Originally, light is an effective tool that has been used in the treatment of diseases for ages. The effects of combination of specific dyes with light illumination was demonstrated at the beginning of 20th century and novel PDT approaches have been developed ever since. Main strategies of current studies are to reduce off-target effects and improve pharmacokinetic properties. Given the high interest and vast literature about the topic, approval of PDT as the first drug/device combination by the FDA should come as no surprise. PDT consists of two stages of treatment, combining light energy with a PS in order to destruct tumor cells after activation by light. In general, PDT has fewer side effects and toxicity than chemotherapy and/or radiotherapy. In addition to the purpose of treatment, several types of PSs can be used for diagnostic purposes for tumors. Such approaches are called photodynamic diagnosis (PDD). In this Review, we provide a general overview of the clinical applications of PDT in cancer, including the diagnostic and therapeutic approaches. Assessment of PDT therapeutic efficacy in the clinic will be discussed, since identifying predictors to determine the response to treatment is crucial. In addition, examples of PDT in various types of tumors will be discussed. Furthermore, combination of PDT with other therapy modalities such as chemotherapy, radiotherapy, surgery and immunotherapy will be emphasized, since such approaches seem to be promising in terms of enhancing effectiveness against tumor. The combination of PDT with other treatments may yield better results than by single treatments. Moreover, the utilization of lower doses in a combination therapy setting may cause less side effects and better results than single therapy. A better understanding of the effectiveness of PDT in a combination setting in the clinic as well as the optimization of such complex multimodal treatments may expand the clinical applications of PDT.

Lung cancer is the leading cause of cancer-associated deaths accounting for 24% of all cancer deaths. As a crucial phase of tumor progression, lung cancer metastasis is linked to over 70% of these mortalities. In recent years, exosomes have received increasing research attention in their role in the induction of carcinogenesis and metastasis in the lung. In this review, recent studies on the contribution of exosomes to lung cancer metastasis are discussed, particularly highlighting the role of lung tumor-derived exosomes in immune system evasion, epithelial-mesenchymal transition, and angiogenesis, and their involvement at both the pre-metastatic and metastatic phases. The clinical application of exosomes as therapeutic drug carriers, their role in antitumor drug resistance, and their utility as predictive biomarkers in diagnosis and prognosis are also presented. The metastatic activity, a complex multistep process of cancer cell invasion, survival in blood vessels, attachment and subsequent colonization of the host's organs, is integrated with exosomal effects. Exosomes act as functional mediating factors in cell–cell communication, influencing various steps of the metastatic cascade. To this end, lung cancer cell-derived exosomes enhance cell proliferation, angiogenesis, and metastasis, regulate drug resistance, and antitumor immune activities during lung carcinogenesis, and are currently being explored as an important component in liquid biopsy assessment for diagnosing lung cancer. These nano-sized extracellular vesicles are also being explored as delivery vehicles for therapeutic molecules owing to their unique properties of biocompatibility, circulatory stability, decreased toxicity, and tumor specificity. The current knowledge of the role of exosomes highlights an array of exosome-dependent pathways and cargoes that are ripe for exploiting therapeutic targets to treat lung cancer metastasis, and for predictive value assessment in diagnosis, prognosis, and anti-tumor drug resistance.

Carbon ion radiation therapy (CIRT) is the most advanced radiation therapy (RT) available and offers new opportunities to improve cancer treatment and research. CIRT has a unique physical and biological advantage that allow them to kill tumor cells more accurately and intensively. So far, CIRT has been used in almost all types of malignant tumors, and showed good feasibility, safety and acceptable toxicity, indicating that CIRT has a wide range of development and application prospects. In addition, in order to improve the biological effect of CIRT, scientists are also trying to investigate related sensitizing agents to enhance the killing ability of tumor cells, which has attracted extensive attention. In this review, we tried to systematically review the rationale, advantages and problems, the clinical applications and the sensitizing agents of the CIRT. At the same time, the prospects of the CIRT in were prospected. We hope that this review will help researchers interested in CIRT, sensitizing agents, and radiotherapy to understand their magic more systematically and faster, and provide data reference and support for bioanalysis, clinical medicine, radiotherapy, heavy ion therapy, and nanoparticle diagnostics.

Liver diseases are a major health concern globally, and are associated with poor survival and prognosis of patients. This creates the need for patients to accept the main alternative treatment of liver transplantation to prevent progression to end-stage liver disease. Investigation of the molecular mechanisms underpinning complex liver diseases and their pathology is an emerging goal of stem cell scope. Human induced pluripotent stem cells (hiPSCs) derived from somatic cells are a promising alternative approach to the treatment of liver disease, and a prospective model for studying complex liver diseases. Here, we review hiPSC technology of cell reprogramming and differentiation, and discuss the potential application of hiPSC-derived liver cells, such as hepatocytes and cholangiocytes, in refractory liver-disease modeling and treatment, and drug screening and toxicity testing. We also consider hiPSC safety in clinical applications, based on genomic and epigenetic alterations, tumorigenicity, and immunogenicity.

Background: To summarize the distribution of pathogenic bacteria in elderly Chinese patients with pneumonia and provide guidance for the clinical application of antibiotics.Methods: The electronic databases of PubMed, Embase, Cochrane library, and China National Knowledge Infrastructure were searched. The primary outcomes included the prevalence of gram-positive cocci, gram-negative bacilli, and fungus. The summary prevalence and 95% confidence interval (CI) were calculated using the random-effects model.Results: A total of 17 retrospective studies reporting a total of 5,729 elderly patients with pneumonia were selected for final analysis. The summary prevalence of gram-positive cocci was 25% (95% CI: 20–30%; p < 0.001), whereas the prevalence of gram-negative bacilli was 56% (95% CI: 46–67%; p < 0.001). Moreover, the pooled prevalence of fungus in elderly patients with pneumonia was 11% (95% CI: 8–14%; p < 0.001). The most common gram-positive cocci were Staphylococcus aureus (ES: 8%; 95% CI: 6–11%; p Streptococcus hemolyticus (ES: 7%; 95% CI: 6–8%; p < 0.001), and Streptococcus pneumoniae (ES: 5%; 95% CI: 3–7%; p < 0.001). Pseudomonas aeruginosa (ES: 18%; 95% CI: 14–22%; p Klebsiella pneumoniae (ES: 14%; 95% CI: 11–18%; p Candida albicans in elderly patients with pneumonia was 6% (95% CI: 5–8%; p < 0.001).Conclusions: The findings demonstrated the comprehensive distribution of pathogenic bacteria in elderly Chinese patients with pneumonia, which could guide further antibiotic therapies.

Breast cancer (BC) is the most frequent cancer among women worldwide and is the leading cause of cancer-related deaths in women. Cancer cells with stem cell-like features and tumor-initiating potential contribute to drug resistance, tumor recurrence, and metastasis. To achieve better clinical outcomes, it is crucial to eradicate both bulk BC cells and breast cancer stem cells (BCSCs). Salinomycin, a monocarboxylic polyether antibiotic isolated from Streptomyces albus, can precisely kill cancer stem cells (CSCs), particularly BCSCs, by various mechanisms, including apoptosis, autophagy, and necrosis. There is increasing evidence that salinomycin can inhibit cell proliferation, invasion, and migration in BC and reverse the immune-inhibitory microenvironment to prevent tumor growth and metastasis. Therefore, salinomycin is a promising therapeutic drug for BC. In this review, we summarize established mechanisms by which salinomycin protects against BC and discuss its future clinical applications.

Optical coherence tomography angiography (OCTA) is the most relevant evolution based on optical coherence tomography (OCT). OCTA can present ocular vasculature, show detailed morphology for assessment, and quantify vessel parameters without intravenous dye agent. Research on the anterior segment OCTA (AS-OCTA) is only in its initial phase, and its advances in clinical diagnosis and treatment efficacy evaluations require a detailed comparison to traditional imaging methods. In this review of AS-OCTA, we summarize its technical features, imaging advances, current clinical applications in various eye diseases, as well as its limitations and potential future directions. AS-OCTA offers potential advantages in ophthalmic imaging, and with further development it could become a common tool in the near future.

Circulating Tumor Cells (CTCs) are cancer cells that split away from the primary tumor and appear in the circulatory system as singular units or clusters, which was first reported by Dr. Thomas Ashworth in 1869. CTCs migrate and implantation occurs at a new site, in a process commonly known as tumor metastasis. In the case of breast cancer, the tumor cells often migrate into locations such as the lungs, brain, and bones, even during the early stages, and this is a notable characteristic of breast cancer. Survival rates have increased significantly over the past few decades because of progress made in radiology and tissue biopsy, making early detection and diagnosis of breast cancer possible. However, liquid biopsy, particularly that involving the collection of CTCs, is a non-invasive method to detect tumor cells in the circulatory system, which can be easily isolated from human plasma, serum, and other body fluids. Compared to traditional tissue biopsies, fluid sample collection has the advantages of being readily available and more acceptable to the patient. It can also detect tumor cells in blood earlier and in smaller numbers, possibly allowing for diagnosis prior to any tumor detection using imaging methods. Because of the scarcity of CTCs circulating in blood vessels (only a few CTCs among billions of erythrocytes and leukocytes), thorough but accurate detection methods are particularly important for further clinical applications.

The umbilical cord has been proved to be an easy-access, reliable, and useful source of mesenchymal stem cells (MSC) for clinical applications due to its primitive, immunomodulatory, non-immunogenic, secretory and paracrine, migratory, proliferative, and multipotent properties. This set of characteristics has recently attracted great research interest in the fields of nanotechnology and regenerative medicine and cellular therapy. Accumulating evidence supports a pronounced therapeutic potential of MSC in many different pathologies, from hematology to immunology, wound-healing, tissue regeneration, and oncology. Diabetes mellitus, branded the epidemic of the century, is considered a chronic metabolic disorder, representing a major burden for health system sustainability and an important public health challenge to modern societies. The available treatments for type 2 diabetes mellitus (T2DM) still rely mainly on combinations of oral antidiabetic agents with lifestyle and nutritional adjustments. Despite the continuous development of novel and better hypoglycemic drugs, their efficacy is limited in the installment and progression of silent T2DM complications. T2DM comorbidities and mortality rates still make it a serious, common, costly, and long-term manageable disease. Recently, experimental models, preclinical observations, and clinical studies have provided some insights and preliminary promising results using umbilical cord MSCs to treat and manage diabetes. This review focuses on the latest research and applications of human-derived umbilical cord MSC in the treatment and management of T2DM, exploring and systematizing the key effects of both umbilical cord MSC and its factor-rich secretome accordingly with the major complications associated to T2DM.

Cancer has become the leading cause of death in recent years. As great advances in medical treatment, emerging therapies of various cancers have been developed. Current treatments include surgery, radiotherapy, chemotherapy, immunotherapy, and targeted therapy. Aptamers are synthetic ssDNA or RNA. They can bind tightly to target molecules due to their unique tertiary structure. It is easy for aptamers to be screened, synthesized, programmed, and chemically modified. Aptamers are emerging targeted drugs that hold great potentials, called therapeutic aptamers. There are few types of therapeutic aptamers that have already been approved by the US Food and Drug Administration (FDA) for disease treatment. Now more and more therapeutic aptamers are in the stage of preclinical research or clinical trials. This review summarized the screening and development of therapeutic aptamers against different types of cancer cells.

Background and objective: Cancer is a life-threatening disease worldwide and current standard therapy cannot fulfill all clinical needs. Chinese herbal injections have been widely used for cancer in Chinese and Western hospitals in China. This study aimed to apply evidence mapping in order to provide an overview of the clinical application of Chinese herbal injections in cancer care based on randomized controlled trials, systematic reviews, and meta-analyses.Methods and results: Seven databases were systematically searched for eligible randomized controlled trials, systematic reviews, and meta-analyses for ten Chinese herbal injections used in cancer treatment and covered in the Chinese national essential health insurance program. Excel 2016 and RStudio were used to integrate and process the data.In total 366 randomized controlled trials and 48 systematic reviews and meta-analyses were included in the evidence mapping of herbal medicines including; Compound Kushen, Shenqi Fuzheng, Aidi, Kangai, Kanglaite, Xiaoaiping, Cinobufacin, Brucea javanica oil emulsion, Polyporus polysaccharide injection, and Astragalus polysaccharide for injection. Health insurance restricts the scope of clinical application for these herbal injections. The numbers of studies published increased, especially around 2013–2015. The most studied cancer types were lung cancer (118, 32.2%), colorectal cancer (39, 10.7%), and gastric cancer (39, 10.7%), and the most used injections were Compound Kushen (78, 21.3%), Shenqi Fuzheng (76, 20.8%), and Aidi (63, 17.2%). The most consistently reported benefits were observed for Compound Kushen, Shenqi Fuzheng, Aidi, and Kangai for tumor response, quality of life, myelosuppression, and enhancing immunity.Conclusion: The current evidence mapping provides an overview of the outcomes and effects of Chinese herbal injections used in cancer care, and offers information on their clinical application which warrants further evidence-based research in order to inform clinical and policy decision-making.

Botulinum toxin (BTX) is used in various ways such as temporarily resolving muscular problems in musculoskeletal temporomandibular disorders, inducing a decrease in bruxism through a change in muscular patterns in a patient’s bruxism, and solving problems in patients with tension headache. And also, BTX is widely used in cosmetic applications for the treatment of facial wrinkles after local injection, but conditions such as temporomandibular joint disorders, headache, and neuropathic facial pain could be treated with this drug. In this report, we will discuss the clinical use of BTX for facial wrinkle, intraoral ulcer, and cranio-maxillofacial pain with previous studies and share our case.

This special issue of Brain Circulation presents cutting-edge research discoveries in stem cell-based regenerative medicine. Each article highlights recent advances in the fields of neurodegeneration and regenerative medicine. The selected contributions offer the groundwork for translating stem cell therapy to the clinic for treating central nervous system disorders. This issue is dedicated to Dr. Teng Ma, who passed away on May 18, 2019. Dr. Ma devoted a significant portion of his life in advancing biomedical engineering, including the utility of 3-dimensional bioreactor and magnetic resonance imaging, as a key element of the biological and therapeutic applications of stem cells for neurological disorders. Dr. Ma's research vision is celebrated in this compilation of ten articles on stem cell-based regenerative medicine.

Context Brainstem tumour surgery is difficult, and accidents can easily occur. Objective To explore the effect of dexmedetomidine hydrochloride on brainstem tumour surgery. Design, setting and participants A total of 60 patients with brainstem tumours successfully operated on by our hospital from March 2016 to March 2018 were selected as subjects. Interventions These patients were randomised into two groups: the research group (n = 30) and control group (n = 30). Patients in the control group were given propofol together with a placebo (0.9% sodium chloride solution) to maintain anaesthesia after general anaesthesia, while patients in the research group were supplemented with dexmedetomidine hydrochloride. Main outcome measure Awakening time, overall stability of various indicators in the operation and adverse reactions during the awakening period were observed. Results The results revealed that patients in the research group had a longer awakening time, higher mean stability rate, higher effective rate and less incidence of adverse reactions during the awakening period than the control group; the differences were all statistically significant (P

Summary Limited visualization of the fetal heart and vessels by fetal ultrasound due to suboptimal fetal position, patient habitus and skeletal calcification may lead to missed diagnosis, overdiagnosis and parental uncertainty. Counselling and delivery planning may in those cases also be tentative. The recent fetal cardiac magnetic resonance (CMR) reconstruction method utilizing tiny golden‐angle iGRASP (iterative Golden‐angle RAdial Sparse Parallel MRI) allows for cine imaging of the fetal heart for use in clinical practice. This case describes an unbalanced common atrioventricular canal where limited ultrasound image quality and visibility of the aortic arch precluded confirming or ruling out presence of a ventricular septal defect. Need of prostaglandins or neonatal intervention was thus uncertain. Cardiovascular magnetic resonance imaging confirmed ultrasound findings and added value by ruling out a significant ventricular septal defect and diagnosing arch hypoplasia. This confirmed the need of patient relocation for delivery at a paediatric cardiothoracic surgery centre and prostaglandins could be initiated before the standard postnatal ultrasound. The applied CMR method can thus improve diagnosis of complicated fetal cardiac malformation and has direct clinical impact.

Background: Intestinal ischemia reperfusion injury is a frequent clinical damage, in which the oxidative stress and inflammation play an important role. Interleukin-1 receptor antagonist (IL-1Ra) is a natural anti-inflammatory factor, however, its effect on intestinal ischemia reperfusion injury remains unclear. Methods: The rat model of intestinal I/R was induced by occlusion (for 60 min) and reopening (for 60 min) of superior mesenteric artery. The rats were randomly divided into the following 5 groups: sham-operation(S), model (I/R),10 mg/kgIL-1Ra + I/R (C1),20 mg/kgIL-1Ra + I/R (C2), and30 mg/kgIL-1Ra + I/R (C3). Results: In this study it was the first time to confirm that IL-1Ra had a significant protection against the intestinal ischemia reperfusion injury. IL-1Ra not only effectively inhibited the expression of inflammatory factors (such as IL-1β, IL-6 and TNF-α) and the activation of neutrophil in intestinal tissues, but also decreased the death of intestinal cells and the damages of intestinal tissues. Interestingly, besides anti-inflammation effect, it was also found that IL-1Ra possessed a significant inhibitory effect on the oxidative stress caused by ischemia/reperfusion injury. Furthermore, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1), and the phosphorylation level of Nrf2 were greatly promoted by IL-1Ra. At the same time, IL-1Ra inhibited the mitogen-activated protein kinase (MAPKs) pathway. Conclusion: IL-1Ra had the protective effect against intestinal ischemia reperfusion injury, its mechanism included anti-inflammation and anti-oxidative stress in which the Nrf2/HO-1 pathway played an important role. The above-mentioned results may extend the clinical application of IL-1Ra in the treatment of intestinal ischemia reperfusion injury. Keywords: Interleukin 1 receptor antagonist (IL-1Ra), Intestinal ischemia reperfusion injury, Protective effect, Nrf2/HO-1, Clinical application

International audience; Following the basis of tissue engineering (Cells-Scaffold-Bioactive molecules), regenerative endodontic has emerged as a new concept of dental treatment. Clinical procedures have been proposed by endodontic practitioners willing to promote regenerative therapy. Preserving pulp vitality was a first approach. Later procedures aimed to regenerate a vascularized pulp in necrotic root canals. However, there is still no protocol allowing an effective regeneration of necrotic pulp tissue either in immature or mature teeth. This review explores in vitro and preclinical concepts developed during the last decade, especially the potential use of stem cells, bioactive molecules, and scaffolds, and makes a comparison with the goals achieved so far in clinical practice. Regeneration of pulp-like tissue has been shown in various experimental conditions. However, the appropriate techniques are currently in a developmental stage. The ideal combination of scaffolds and growth factors to obtain a complete regeneration of the pulp-dentin complex is still unknown. The use of stem cells, especially from pulp origin, sounds promising for pulp regeneration therapy, but it has not been applied so far for clinical endodontics, in case of necrotic teeth. The gap observed between the hope raised from in vitro experiments and the reality of endodontic treatments suggests that clinical success may be achieved without external stem cell application. Therefore, procedures using the concept of cell homing, through evoked bleeding that permit to recreate a living tissue that mimics the original pulp has been proposed. Perspectives for pulp tissue engineering in the near future include a better control of clinical parameters and pragmatic approach of the experimental results (autologous stem cells from cell homing, controlled release of growth factors). In the coming years, this therapeutic strategy will probably become a clinical reality, even for mature necrotic teeth.

Fibroblast growth factor 21 (FGF21) regulates many crucial biological processes in human and mammals, particularly metabolic modulation and protective effect after injury. Therefore, determining complex regulatory mechanisms and elucidating the signaling pathway may greatly promote the prevention, diagnosis, and treatment of related injury and metabolic diseases. This review focused on the metabolic modulation and protective effect of FGF21 and summarized the molecular mechanisms and clinical research developments.

Introduction Coronavirus disease 2019 (COVID‐19) has spread all over the world showing high transmissibility. Many studies have proposed diverse diagnostic methods based on deep learning using chest X‐ray images focusing on performance improvement. In reviewing them, this study noticed that evaluation results might be influenced by dataset organization. Therefore, this study identified whether the high‐performance values can prove the clinical application potential. Methods This study selected chest X‐ray image databases which have been widely applied in previous studies. One database includes images for COVID‐19, while the others consist of normal and pneumonia images. Then, the COVID‐19 classification model was designed and trained on diverse database compositions and evaluated using confusion matrix‐based metrics. Also, each database was analyzed by graphical representation methods. Results The performance was significantly different according to dataset composition. Overall, higher performance was identified on the dataset organized with different databases for each class, compared with the dataset from same database. Also, there were significant differences in the image characteristics between different databases. Conclusions The experimental results indicate that model may be trained based on differences of the image characteristics between databases and not on lesion features. This shows that evaluation metrics can be influenced by dataset organization, and high metric values would not directly mean the potential for clinical application. These emphasize the importance of suitable dataset organization for applying COVID‐19 diagnosis methods to real clinical sites. Radiologists should sufficiently understand about this issue as actual user of these methods.

Simple Summary Precise identification and annotation of mutations are of utmost importance in clinical oncology. Insights of the DNA sequence can provide meaningful knowledge to unravel the underlying genetics of disease. Hence, tailoring of personalized medicine often relies on specific genomic alteration for treatment efficacy. The aim of this review is to highlight that sequencing harbors much more than just four nucleotides. Moreover, the gradual transition from first to second generation sequencing technologies has led to awareness for choosing the most appropriate bioinformatic analytic tools based on the aim, quality and demand for a specific purpose. Thus, the same raw data can lead to various results reflecting the intrinsic features of different datamining pipelines. Abstract Data analysis has become a crucial aspect in clinical oncology to interpret output from next-generation sequencing-based testing. NGS being able to resolve billions of sequencing reactions in a few days has consequently increased the demand for tools to handle and analyze such large data sets. Many tools have been developed since the advent of NGS, featuring their own peculiarities. Increased awareness when interpreting alterations in the genome is therefore of utmost importance, as the same data using different tools can provide diverse outcomes. Hence, it is crucial to evaluate and validate bioinformatic pipelines in clinical settings. Moreover, personalized medicine implies treatment targeting efficacy of biological drugs for specific genomic alterations. Here, we focused on different sequencing technologies, features underlying the genome complexity, and bioinformatic tools that can impact the final annotation. Additionally, we discuss the clinical demand and design for implementing NGS.

Stroke is the leading cause of death worldwide, and its treatment remains a challenge. Complex pathological processes are involved in stroke, which causes a reduction in the supply of oxygen and energy to the brain that triggers subsequent cascade events, such as oxidative stress, inflammatory responses and apoptosis, resulting in brain injury. Stroke is a devastating disease for which there are few treatments, but physical rehabilitation can help improve stroke recovery. Although there are very few treatments for stroke patients, the discovery of fibroblast growth factors (FGFs) in mammals has led to the finding that FGFs can effectively treat stroke in animal models. As presented in this review, FGFs play essential roles by functioning as homeostatic factors and controlling cells and hormones involved in metabolism. They could be used as effective therapeutic agents for stroke. In this review, we will discuss the pharmacological actions of FGFs on multiple targets, including their ability to directly promote neuron survival, enhance angiogenesis, protect against blood-brain barrier (BBB) disruption, and regulate microglial modulation, in the treatment of ischemic stroke and their theoretical mechanisms and actions, as well as the therapeutic potential and limitations of FGFs for the clinical treatment of stroke.

The morbidity and mortality caused by invasive fungal infections are increasing across the globe due to developments in transplant surgery, the use of immunosuppressive agents, and the emergence of drug-resistant fungal strains, which has led to a challenge in terms of treatment due to the limitations of three classes of drugs. Hence, it is imperative to establish effective strategies to identify and design new antifungal drugs. Drug repurposing is a potential way of expanding the application of existing drugs. Recently, various existing drugs have been shown to be useful in the prevention and treatment of invasive fungi. In this review, we summarize the currently used antifungal agents. In addition, the most up-to-date information on the effectiveness of existing drugs with antifungal activity is discussed. Moreover, the antifungal mechanisms of existing drugs are highlighted. These data will provide valuable knowledge to stimulate further investigation and clinical application in this field. Key points • Conventional antifungal agents have limitations due to the occurrence of drug-resistant strains. • Non-antifungal drugs act as antifungal agents in various ways toward different targets. • Non-antifungal drugs with antifungal activity are demonstrated as effective antifungal strategies.

ObjectivesWhole exome sequencing (WES) has been widely used to detect genetic disorders in critically ill children. Relevant data are lacking in pediatric intensive care units (PICUs) of China. This study aimed to investigate the spectrum of monogenic disorders, the diagnostic yield and clinical utility of WES from a PICU in a large children’s hospital of China.MethodsFrom July 2017 to February 2020, WES was performed in 169 critically ill children with suspected monogenic diseases in the PICU of Beijing Children’s Hospital. The clinical features, human phenotype ontology (HPO) terms, and assessment of clinical impact were analyzed.ResultsThe media age of the enrolled children was 10.5 months (range, 1 month to 14.8 years). After WES, a total of 43 patients (25%) were diagnosed with monogenic disorders. The most common categories of diseases were metabolic disease (33%), neuromuscular disease (19%), and multiple deformities (14%). The diagnosis yield of children with “metabolism/homeostasis disorder” and “growth delay” or “ocular anomalies” was higher than that of children without these features. In addition, the diagnosis rate increased when more features were observed in children. The results of WES had an impact on the treatment for 30 cases (70%): (1) change of treatment (n= 11), (2) disease monitoring initiation (n= 18), (3) other systemic evaluation (n= 3), (4) family intervention (n= 2), and (5) rehabilitation and redirection of care toward palliative care (n= 12).ConclusionWES can be used as an effective diagnostic tool in the PICU of China and has an important impact on the treatment of patients with suspected monogenic conditions.