Extracellular vesicles (EVs) function as potent mediators of intercellular communication for many in vivo processes, contributing to both health and disease related conditions. Given their biological origins and diverse functionality from correspondingly unique “cargo” compositions, both endogenous and modified EVs are garnering attention as promising therapeutic modalities and vehicles for targeted therapeutic delivery applications. Their diversity in composition, however, has revealed a significant need for more comprehensive analytical-based characterization methods, and manufacturing processes that are consistent and scalable. In this review, we explore the dynamic landscape of EV research and development efforts, ranging from novel isolation approaches, to their analytical assessment through novel characterization techniques, and to their production by industrial-scale manufacturing process considerations. Expanding the horizon of these topics to EVs for in-human applications, we underscore the need for stringent development and adherence to Good Manufacturing Practice (GMP) guidelines. Wherein, the intricate interplay of raw materials, production in bioreactors, and isolation practices, along with analytical assessments compliant with the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines, in conjunction with reference standard materials, collectively pave the way for standardized and consistent GMP production processes.

Animals ; Monkeypox/drug therapy* ; Antiviral Agents/therapeutic use* ; Phosphoric Monoester Hydrolases/therapeutic use* ; Macaca fascicularis

OBJECTIVE To provide reference for scientifi c and standardized development of clinical comprehensive evaluation of drugs in China. METHODS Guided by the theory of total quality management （TQM），drawing lessons from the successful experience of the British and German conducting evaluation ，combining with plan-do-check-act cycle and other quality management methods and tools ，drug clinical comprehensive evaluation of total quality management system was constructed in accordance with the requirements for our country related policy and local practice. RESULTS & CONCLUSIONS To construct total quality management system of clinical comprehensive evaluation of drugs in China from 5 aspects of organization system ，management process，assessment system ，evaluation and supervision platform ，support and guarantee mechanism. The organization system included national ，provincial and medical institutions ；management process should focus on the key links in the 3 stages of theme selection，evaluation and implementation ，and result transformation and application ；assessment system ，evaluation and supervision platform，support and guarantee mechanism should be established together so as to further improve the scientificity ，rationality， practicality and standardization of total quality management of clinical comprehensive evaluation of drugs. The development of total quality management is an effective starting point to promote the continual improvement of the drug clinical comprehensive evaluation；relevant government departments and the implementation of evaluation of medical institutions should further set up quality management consciousness ，establish report quality feedback mechanism and the results co-constructing and sharing mechanism and strengthen professional personnel training and innovation synergy regulation mode to ensure that the authenticity and reliability of evaluation results.

Background: The use of translaminar screws may serve as a viable salvage method for complicated cases. To our understanding, the study of the feasibility of translaminar screw insertion in the actual entire subaxial cervical spine has not been carried out yet. The purpose of this study was to report the feasibility of translaminar screw insertion in the entire subaxial cervical spine. Methods: Eighteen cadaveric spines were harvested from C3 to C7 and 1-mm computed tomography (CT) scans and three-dimensional reconstructions were created to exclude any bony anomaly. Thirty anatomically intact segments were collected (C3, 2; C4, 3; C5, 3; C6, 8; and C7, 14), and randomly arranged. Twenty-one segments were physically separated at each vertebral level (group S), while 9 segments were not separated from the vertebral column and left in situ (group N–S). CT measurement of lamina thickness was done for both group S and group N–S, and manual measurement of various length and angle was done for group S only. Using the trajectory proposed by the previous studies, translaminar screws were placed at each level. Screw diameter was the same or 0.5 mm larger than the proposed diameter based on CT measurement. Post-insertion CT was performed. Cortical breakage was checked either visually or by CT. Results: When 1° and 2° screws of the same size were used, medial cortex breakage was found 13% and 33% of the time, respectively. C7 was relatively safer than the other levels. With larger-sized screws, medial cortex breakage was found in 47% and 46% of 1° and 2° screws, respectively. There were no facet injuries due to the screws in group N–S. Conclusions Translaminar screw insertion in the subaxial cervical spine is feasible only when the lamina is thick enough to avoid any breakage that could lead to further complications. The authors do not recommend inserting translaminar screws in the subaxial cervical spine except in some salvage cases in the presence of a thick lamina.

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.
Adenocarcinoma of Lung/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Carcinoma, Squamous Cell/genetics* ; Genetic Heterogeneity ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Lung Neoplasms/genetics* ; Polymorphism, Single Nucleotide

Arsenic/toxicity* ; Bangladesh ; Female ; Humans ; Infant, Newborn ; Pregnancy ; Premature Birth/chemically induced* ; Rural Population ; Zinc

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low. Genetic risk associations of relevance to Asia include human leucocyte antigen (HLA)-B*1502 with carbamazepine SCAR, and HLA-B*5801 with allopurinol SCAR in some Asian ethnic groups. There remains a lack of safe and accurate diagnostic tests for antituberculous drug allergy, other than relatively high-risk desensitization regimes to first-line antituberculous therapy. NSAID hypersensitivity is common among both adults and children in Asia, with regional differences in phenotype especially among adults. Low dose aspirin desensitization is an important therapeutic modality in individuals with cross-reactive NSAID hypersensitivity and coronary artery disease following percutaneous coronary intervention. Skin testing allows patients with radiocontrast media hypersensitivity to confirm the suspected agent and test for alternatives, especially when contrasted scans are needed for future monitoring of disease relapse or progression, especially cancers.
Adult ; Allopurinol ; Anaphylaxis ; Anti-Bacterial Agents ; Asia ; Asian Continental Ancestry Group ; Aspirin ; Asthma ; Carbamazepine ; Child ; Cicatrix ; Contrast Media ; Coronary Artery Disease ; Diagnostic Tests, Routine ; Drug Hypersensitivity ; Ethnic Groups ; Humans ; Hypersensitivity ; Penicillins ; Percutaneous Coronary Intervention ; Phenotype ; Recurrence ; Skin Tests

Genetics ; Laboratories ; Technology ; standards ; United States

As a novel intervention, whole body periodic acceleration (WBPA) shows a variety of benefits to the cardiovascular system, such as reducing pulmonary arteria hypertension (PAH), improving coronary flow reserve (CFR) and increasing blood perfusion of organs as well as tissues. The underlying mechanisms of WBPA may lie in the increase of blood flow rate and endothelium shear stress, activation of phosphoinositide 3-kinase/serine threonine kinase (PI3K-Akt) and mitogen extracellular signal regulated kinases/extracellular signal regulated kinase (MEK-ERK1/2) signal pathway and the release of nitric oxide.