Assessing the interplay between off-target promiscuity, cytotoxicity, and tolerability in rodents to improve the safety profile of novel anti-malarial plasmepsin X inhibitors.

Within drug development, high off-target promiscuity as well as potent cytotoxicity, are associated with a high attrition rate. We investigated the safety profile of novel plasmepsin X (PMX) inhibitors for the treatment of malaria. In our screening cascade, a total of 249 PMX compounds were profiled in a panel of in vitro secondary pharmacology assays containing 44 targets (SafetyScreen44™ panel) and in a cytotoxicity assay in HepG2 cells using ATP as an endpoint. Six of the lead compounds were subsequently tested in a 7-day rat toxicology study, and/or in a cardiovascular study in guinea pigs. Overall, compounds with high cytotoxicity in HepG2 cells correlated with high promiscuity (off-target hit rate >20%) in the SafetyScreen44™ panel and were associated with poor tolerability in vivo (decedents, morbidity, adverse clinical signs, or severe cardiovascular effects). Some side effects observed in rats or guinea pigs could putatively be linked with hits in the secondary pharmacological profiling, such as the M1 or M2 muscarinic acetylcholine receptor, opioid µ and/or κreceptors or hERG/CaV1.2/Na+ channels, which were common to > 50% the compounds tested in vivo. In summary, compounds showing high cytotoxicity and high promiscuity are likely to be poorly tolerated in vivo. However, such associations do not necessarily imply a causal relationship. Identifying the targets that cause these undesirable effects is key for early safety risk assessment. A tiered approach, based on a set of in vitro assays, helps selecting the compounds with highest likelihood of success to proceed to in vivo toxicology studies.

Deliberative process of health technology reassessment by health technology assessment agency in Korea.

In 2019, the National Evidence-based Healthcare Collaborating Agency (NECA) in Korea established a health technology reassessment (HTR) system to manage the life cycle of health technologies and develop operational measures promoting the efficient use of healthcare resources. The purpose of this study is to introduce the detailed implementation process and practical functional methods of the HTR implemented by NECA.The HTR is a structured multidisciplinary method for analyzing health technologies currently used in the healthcare system based on the latest information on parameters, such as clinical safety, effectiveness, and cost-effectiveness of optimizing the use of healthcare resources as well as social and ethical issues. All decision-making stages of the HTR are carefully reviewed and transparently managed. The HTR committee makes significant decisions, and the subcommittee decides the details related to the assessment process.Since the pilot began in 2018, 262 cases have been reassessed, of which, 126 cases (48.1 percent) were health services not covered by the National Health Insurance (NHI). Over the past 5 years, approximately 130 recommendations for the in-use technologies were determined by the HTR committee. In the near future, it will be necessary to officially develop and establish a Korean HTR system and a legal foundation to optimize the NHI system.

[Safety considerations for the clinical application of recombinant human growth hormone]. / é‡ç»„äººç”Ÿé•¿æ¿€ç´ ä¸´åºŠåº”ç”¨çš„å®‰å ¨æ€§æ€è€ƒ.

Recombinant human growth hormone (rhGH) is an effective therapeutic drug for improving short stature. Currently, rhGH can be used for various causes of short stature, including growth hormone deficiency, and the expansion of its clinical application has raised concerns about its safety. Based on existing evidence, when rhGH is used in a standardized manner for physiological replacement therapy, its safety profile is favorable. In clinical practice, attention should be focused on short-term safety during rhGH treatment, with the combination of literature evidence and clinical experience. There is still no definitive conclusion on the long-term safety due to insufficient duration of rhGH treatment. This paper reviews the possible adverse events that may occur during rhGH treatment and their risk control measures, aiming to help clinical physicians understand the overall safety of rhGH treatment and improve its clinical standardization.

Developing an integrated clinical decision support system for the early identification and management of kidney disease-building cross-sectoral partnerships.

BACKGROUND: The burden of chronic conditions is growing in Australia with people in remote areas experiencing high rates of disease, especially kidney disease. Health care in remote areas of the Northern Territory (NT) is complicated by a mobile population, high staff turnover, poor communication between health services and complex comorbid health conditions requiring multidisciplinary care. AIM: This paper aims to describe the collaborative process between research, government and non-government health services to develop an integrated clinical decision support system to improve patient care. METHODS: Building on established partnerships in the government and Aboriginal Community-Controlled Health Service (ACCHS) sectors, we developed a novel digital clinical decision support system for people at risk of developing kidney disease (due to hypertension, diabetes, cardiovascular disease) or with kidney disease. A cross-organisational and multidisciplinary Steering Committee has overseen the design, development and implementation stages. Further, the system's design and functionality were strongly informed by experts (Clinical Reference Group and Technical Working Group), health service providers, and end-user feedback through a formative evaluation. RESULTS: We established data sharing agreements with 11 ACCHS to link patient level data with 56 government primary health services and six hospitals. Electronic Health Record (EHR) data, based on agreed criteria, is automatically and securely transferred from 15 existing EHR platforms. Through clinician-determined algorithms, the system assists clinicians to diagnose, monitor and provide guideline-based care for individuals, as well as service-level risk stratification and alerts for clinically significant events. CONCLUSION: Disconnected health services and separate EHRs result in information gaps and a health and safety risk, particularly for patients who access multiple health services. However, barriers to clinical data sharing between health services still exist. In this first phase, we report how robust partnerships and effective governance processes can overcome these barriers to support clinical decision making and contribute to holistic care.

An Integrated Approach to the Anti-Inflammatory, Antioxidant, and Genotoxic Potential of Portuguese Traditional Preparations from the Bark of Anacardium occidentale L.

Anacardium occidentale L. stem bark Traditional Herbal Preparations (AoBTHPs) are widely used in traditional medicine to treat inflammatory conditions, such as diabetes. The present study aims to evaluate the anti-inflammatory, antioxidant, and genotoxic potential of red and white Portuguese AoBTHPs. Using a carrageenan-induced rat paw edema model, a significant anti-edema effect was observed for all tested doses of white AoBTHP (40.2, 71.5, and 127.0 mg/kg) and the two highest doses of red AoB THP (71.5 and 127.0 mg/kg). The anti-edema effect of red AoBTHP's highest dose was much more effective than indomethacin 10 mg/kg, Trolox 30 mg/kg, and Tempol 30 mg/kg. In DPPH, FRAP, and TAC using the phosphomolybdenum method, both types of AoBTHPs showed similar antioxidant activity and no genotoxicity up to 5000 µg/plate in the Ames test. The LC-UV/DAD-ESI/MS fingerprint allowed the identification of gallic and protocatechuic acids as the two main marker compounds and the presence of catechin, epicatechin, epigallocatechin gallate, and ellagic acid in both AoBTHPs. The obtained results support the validation of red and white AoB and their THPs as anti-inflammatory agents and contribute to the possible development of promising new therapeutic options to treat inflammatory conditions.

Next-generation therapeutics for rare genetic disorders.

The therapeutic potential of the human genome has been explored through the development of next-generation therapeutics, which have had a high impact on treating genetic disorders. Classical treatments have traditionally focused on common diseases that require repeated treatments. However, with the recent advancements in the development of nucleic acids, utilizing DNA and RNA to modify or correct gene expression in genetic disorders, there has been a paradigm shift in the treatment of rare diseases, offering more potential one-time cure options. Advanced technologies that use CRISPR-Cas 9, antisense oligonucleotides, siRNA, miRNA, and aptamers are promising tools that have achieved successful breakthroughs in the treatment of various genetic disorders. The advancement in the chemistry of these molecules has improved their efficacy, reduced toxicity, and expanded their clinical use across a wide range of tissues in various categories of human disorders. However, challenges persist regarding the safety and efficacy of these advanced technologies in translating into clinical practice. This review mainly focuses on the potential therapies for rare genetic diseases and considers how next-generation techniques enable drug development to achieve long-lasting curative effects through gene inhibition, replacement, and editing.

Digital Health Safety Matters: A Promising Practice Study into the Adoption of Patient Safety Guidelines in Australia.

A foundation for digitally enabling healthier living is the safe development and use of technology. The practice of digital health safety has emerged from patient harm attributed to failing technologies. The study aimed to investigate how to adopt and implement digital health safety guidelines at scale. Data was collected through an online survey, semi-structured interviews, focus groups, document review, and data mining of artefacts. The findings of this study capture the emerging practice from Australia in a way that offers insights into the problem of practice, patient safety practice, safety culture, and socio-technical factors. The research findings contribute to better understanding of the complexities of balancing digital innovation with patient safety. The four recommendations from the study and the provision of a logic model will support the audience to implement actions toward a safer digital health ecology.

A systematic review comparing the safety, cost and carbon footprint of disposable and reusable laparoscopic devices.

INTRODUCTION: The objective of this systematic review of the literature is to compare a selection of currently utilized disposable and reusable laparoscopic medical devices in terms of safety (1st criteria), cost and carbon footprint. MATERIAL AND METHODS: A search was carried out on electronic databases for articles published up until 6 May 2022. The eligible works were prospective (randomized or not) or retrospective clinical or medical-economic comparative studies having compared disposable scissors, trocars, and mechanical endoscopic staplers to the same instruments in reusable. Two different independent examiners extracted the relevant data. RESULTS: Among the 2882 articles found, 156 abstracts were retained for examination. After comprehensive analysis concerning the safety and effectiveness of the instruments, we included four articles. A study on trocars highlighted increased vascular complications with disposable instruments, and another study found more perioperative incidents with a hybrid stapler as opposed to a disposable stapler. As regards cost analysis, we included 11 studies, all of which showed significantly higher costs with disposable instruments. The results of the one study on carbon footprints showed that hybrid instruments leave four times less of a carbon footprint than disposable instruments. CONCLUSION: The literature on the theme remains extremely limited. Our review demonstrated that from a medical and economic standpoint, reusable medical instruments, particularly trocars, presented appreciable advantages. While there exist few data on the ecological impact, those that do exist are unmistakably favorable to reusable instruments.

Assessment of knowledge, attitude and practice for oxygen therapy among medical staff at the Colonial War Memorial Hospital in Fiji.

BACKGROUND: Oxygen therapy (OT) is a commonly prescribed essential medicine for people of all ages in the management of hypoxia. The adverse effects of inappropriate OT supplementation may be underestimated by health professionals and lead to poor health outcomes among hospitalised patients. Knowledge, attitude and practice (KAP) assessments of medical staff members to OT guidelines are essential to ensure optimal patient care. AIMS: To perform a KAP assessment of OT administration among doctors and nurses employed at the national hospital of Fiji in 2021. METHODS: Prospective cross-sectional study design. KAP assessment was performed with an online questionnaire and clinical observation. RESULTS: The study population (N = 116) consisted of doctors (20.7%) and nurses (79.3%) representing the acute medical, burns, cardiac care, intensive care, surgical and postanaesthetic recovery units. Overall, the proportion of participants who obtained a good score (>70%) was 87% for knowledge, 87.93% for attitudes and 84% for practice. Best knowledge scores were obtained for general OT indications (71%) and scenarios where immediate oxygen application is required (70%). Lowest knowledge scores were for OT contraindications (14%) and oxygen saturation for acute myocardial infarction (32%), asthma (36%) and healthy newborns (43%). The most positive attitudes were in response to the statement that OT guidelines are essential (96%). A total of 78 (80.4%) patients were being cared for with good OT practice. CONCLUSIONS: Good KAP scores were obtained for medical staff in Fiji regarding OT administration. Ongoing professional education activities should include updated training of OT contraindications and optimal oxygen saturation levels for special patient groups.

Clinical safety and tolerability evaluation of Withania somnifera (L.) Dunal (Ashwagandha) root extract in healthy human volunteers.

BACKGROUND: Withania somnifera (L.) Dunal, known as Ashwagandha, is an adaptogen with significant importance in Ayurveda for its potential health benefits in strength ('balavardhan') and muscle growth ('mamsavardhan'). Despite numerous studies on its efficacy, limited research is reported on its clinical safety and tolerability in healthy individuals. OBJECTIVE: This research evaluated the tolerability and safety of standardized Withania somnifera root extract (WSE) capsules (AgeVel®/Witholytin®) at 1000 mg/day dose upon oral administration in healthy male participants. METHOD: A non-randomized, open-label, single-treatment clinical study included eighteen healthy male participants aged 18 to 60. The participants were administered a dose of 500 mg of the WSE capsules twice daily for four weeks. Each capsule contained not less than 7.50 mg of total withanolides. The study evaluated various indicators in a cohort of healthy participants throughout the trial, including vital signs, organ function tests, urine analysis, X-ray and ECG, cardiorespiratory endurance, body fat percentage, lean body weight, adverse events profile, and tolerability of the WSE capsules. RESULTS: The participant's physical, hematological, and biochemical characteristics were normal, and no significant alterations or irregularities were observed in safety metrics like liver, kidney, and thyroid functions after administering AgeVel®/Witholytin®. CONCLUSION: This study found that healthy male participants could consume a standardized WSE at a daily dosage of 1000 mg for four weeks without any adverse effects. Future research should focus on long-term safety assessments in male and female participants.

A qualitative study on the clinical safety and user experiences of female condoms for anal intercourse among men who have sex with men in Shanghai, China.

Objective: This qualitative study aimed to understand the clinical safety, efficacy, and receptiveness of using the female condom (FC) during anal intercourse among men who have sex with men (MSM). Methods: Subjects for this study were recruited from a two-group crossover trial among MSM in Shanghai. The trial consisted of two phases, each including the use of condoms (FC vs. male condom), questionnaires, and in-depth one-on-one interviews. The two phases were separated by a washout period of 4 weeks. The minimum sample size for this study was determined in accordance with the principle of "information saturation." The qualitative data were organized and analyzed using ATLAS.ti version 7. Results: A total of 26 participants from the MSM population were recruited for this study, with 10 assuming the insertive role (i.e., "1"), 8 assuming the receptive role (i.e., "0"), and 8 being versatile (i.e., "0.5"). Each participant completed the crossover trial comprising two phases. The cumulative usage of FCs and male condoms (MCs) amounted to 115 and 127 times, respectively. During the reported sexual encounters, no participants reported incidents of condom rupture, slippage, or other malfunctions. A few participants reported experiencing slight chafing pain, primarily put forward by "0" participants. Apart from those reports, no instances of bleeding, swelling, or allergic reactions were reported. The efficiency of FC in disease prevention, the sexual partner's willingness to use FC, the freshness of FC, and positive sexual experiences were the main reasons for the consistent use of FC for anal sex. Discomfort and pain during sexual activity, the loose design and thick material of FCs, and difficulties in placing FCs were the major obstacles to FC use among MSM. The elements referring to the forehead exhibited varied in importance among "1,", "0," and "0.5" participants. Regarding the willingness to use the FC in the future anal intercourse, 61.54% of participants expressed a positive inclination, 23.08% were uncertain, and 15.38% stated that they would not. "A better sense of security during anal sex" was the main factor affecting willingness among "0" participants and "the sexual pleasure that the FC brought" among "1" participants. Improving the design and technology of FCs and increasing the frequency of use and practice might improve the use skills, which will favor the willingness to use FCs among the MSM population. Conclusion: FCs received positive user feedback from study participants, but distinctions were found in individuals in different sexual roles. Large-scale quantitative studies are needed to evaluate the clinical safety of the FC and its effectiveness in preventing the transmission of STDs during anal intercourse.

Tumor Treating Fields (TTFields) demonstrate antiviral functions in vitro, and safety for application to COVID-19 patients in a pilot clinical study.

Coronaviruses are the causative agents of several recent outbreaks, including the COVID-19 pandemic. One therapeutic approach is blocking viral binding to the host receptor. As binding largely depends on electrostatic interactions, we hypothesized possible inhibition of viral infection through application of electric fields, and tested the effectiveness of Tumor Treating Fields (TTFields), a clinically approved cancer treatment based on delivery of electric fields. In preclinical models, TTFields were found to inhibit coronavirus infection and replication, leading to lower viral secretion and higher cell survival, and to formation of progeny virions with lower infectivity, overall demonstrating antiviral activity. In a pilot clinical study (NCT04953234), TTFields therapy was safe for patients with severe COVID-19, also demonstrating preliminary effectiveness data, that correlated with higher device usage.

Análisis modal de fallos y efectos en las transferencias de pacientes de urgencias a hospitalización / Patient transfers from emergency departments to other in-hospital areas: a failure mode and effects analysis

Objetivo: Este estudio analiza en profundidad el proceso de transferencia de pacientes de urgencias a hospitalización y posibles fallos para evitar problemas de seguridad mediante la identificación de líneas de mejora. Método: Se conformó un grupo de trabajo multidisciplinar compuesto por profesionales asistenciales de urgencias y hospitalización de adultos que, mediante la metodología de análisis modal de fallos y efectos (AMFE), analizó pormenorizadamente el proceso de transferencia de pacientes de urgencias a hospitalización. Para los puntos críticos identificados se estableció el índice de prioridad del riesgo (IPR) en base a su gravedad, probabilidad de aparición y de detección. Resultados: Se identificaron 8 subprocesos y 14 puntos críticos que podrían generar fallos en el proceso de transferencia. Los aspectos relacionados con la administración de medicamentos y el proceso de identificación fueron los que obtuvieron mayores puntuaciones de IPR. Para todos ellos se establecieron acciones de mejora. Se elaboró un procedimiento específico de transferencia de pacientes entre estas áreas y un listado de verificación de ingresos en hospitalización. Conclusiones: Con la metodología AMFE se ha conseguido desgranar un proceso de especial vulnerabilidad como es la transferencia de pacientes de urgencias a hospitalización y definir acciones de mejora en aras de incrementar la seguridad de los pacientes. (AU)

Objectives: To perform an in-depth analysis of the process of transferring patients from an emergency department (ED) to other areas inside a hospital and identify possible points of failure and risk so that strategies for improvement can be developed. Methods: We formed a multidisciplinary group of ED and other personnel working with hospitalized adults. The group applied failure mode and effects analysis (FMEA) to understand the in-hospital transfer processes. A risk priority scoring system was then established to assess the seriousness of each risk and the likelihood it would appear and be detected. Results: We identified 8 transfer subprocesses and 14 critical points at which failures could occur. Processes related to administering medications and identifying patients were the components that received the highest risk priority scores. Improvement strategies were established for all risks. The group created a specific protocol for in-hospital transfers and a checklist to use during handovers. Conclusion: The FMEA method helped the group to identify points when there is risk of failure during patient transfers and to define ways to improve patient safety. (AU)

Patient transfers from emergency departments to other in-hospital areas: a failure mode and effects analysis. / Análisis modal de fallos y efectos en las transferencias de pacientes de urgencias a hospitalización.

OBJECTIVES: To perform an in-depth analysis of the process of transferring patients from an emergency department (ED) to other areas inside a hospital and identify possible points of failure and risk so that strategies for improvement can be developed. MATERIAL AND METHODS: We formed a multidisciplinary group of ED and other personnel working with hospitalized adults. The group applied failure mode and effects analysis (FMEA) to understand the in-hospital transfer processes. A risk priority scoring system was then established to assess the seriousness of each risk and the likelihood it would appear and be detected. RESULTS: We identified 8 transfer subprocesses and 14 critical points at which failures could occur. Processes related to administering medications and identifying patients were the components that received the highest risk priority scores. Improvement strategies were established for all risks. The group created a specific protocol for in-hospital transfers and a checklist to use during handovers. CONCLUSION: The FMEA method helped the group to identify points when there is risk of failure during patient transfers and to define ways to improve patient safety.

OBJETIVO: Este estudio analiza en profundidad el proceso de transferencia de pacientes de urgencias a hospitalización y posibles fallos para evitar problemas de seguridad mediante la identificación de líneas de mejora. METODO: Se conformó un grupo de trabajo multidisciplinar compuesto por profesionales asistenciales de urgencias y hospitalización de adultos que, mediante la metodología de análisis modal de fallos y efectos (AMFE), analizó pormenorizadamente el proceso de transferencia de pacientes de urgencias a hospitalización. Para los puntos críticos identificados se estableció el índice de prioridad del riesgo (IPR) en base a su gravedad, probabilidad de aparición y de detección. RESULTADOS: Se identificaron 8 subprocesos y 14 puntos críticos que podrían generar fallos en el proceso de transferencia. Los aspectos relacionados con la administración de medicamentos y el proceso de identificación fueron los que obtuvieron mayores puntuaciones de IPR. Para todos ellos se establecieron acciones de mejora. Se elaboró un procedimiento específico de transferencia de pacientes entre estas áreas y un listado de verificación de ingresos en hospitalización. CONCLUSIONES: Con la metodología AMFE se ha conseguido desgranar un proceso de especial vulnerabilidad como es la transferencia de pacientes de urgencias a hospitalización y definir acciones de mejora en aras de incrementar la seguridad de los pacientes.

Developing a Core Outcome Set for Assessing Clinical Safety Outcomes of Prostate Cancer in Clinical Trials of Traditional Chinese Medicine: Protocol for a Mixed Methods Study.

BACKGROUND: Among the common malignant tumors in men worldwide, the incidence of prostate cancer ranks second to lung cancer. This disease will bring an economic burden to patients and their families and can reduce the quality of life of patients. Researchers have conducted numerous clinical trials on the efficacy and safety of different interventions in the treatment of prostate cancer with traditional Chinese medicine (TCM) combined with standard treatment regimens. However, the currently published clinical trials exhibit inconsistent and irregular reporting of outcome measures. OBJECTIVE: The objective of this paper is to emphasize the need for a core outcome set (COS) to facilitate future prostate cancer research, aiming to improve the quality of trials and generate high-quality evidence. METHODS: This mixed methods project has three phases, as follows: (1) a scoping review of the literature to identify outcomes that have been reported in clinical trials and systematic reviews of interventions involving TCM for the treatment of prostate cancer as well as a qualitative component using interviews to obtain the views of patients with prostate cancer, their families, and their caregivers who have a history of TCM treatment; (2) a Delphi survey among stakeholders to prioritize the core outcomes-Participants will include traditional Chinese and Western medicine clinicians in prostate cancer-related directions, nurses, and methodology experts who will participate in 2 rounds of the Delphi method expert consultation to score each outcome in the list of outcome indicators; and (3) a face-to-face consensus meeting to discuss and agree on the final COS for the application of TCM in the treatment of prostate cancer. RESULTS: The protocol has been registered in PROSPERO (CRD42022356184) before the start of the review process, and we will initiate the review on August 1, 2023; results should be expected by September 1, 2023. The Delphi survey among stakeholders is expected to start in October 2023. CONCLUSIONS: The development of a core outcome set for assessing clinical safety outcomes of prostate cancer in clinical trials of TCM will provide a significant first step to assist Chinese doctors, researchers, and policy makers. TRIAL REGISTRATION: PROSPERO CRD42022356184; https://tinyurl.com/ysakz74r. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/46794.

La calidad en medicina como obligación deontológica / Quality in medicine as a deontological requirement

La práctica médica tiene dos dimensiones fundamentales una la científica, y otra la humana, y en ambas es esencial el compromiso del médico. La deontología médica, como rama de la ética que se ocupa de los deberes y obligaciones de los médicos, plasma en los códigos de deontología los principios y están dares éticos de obligado cumplimiento, a fin de que la práctica médica pueda garantizar que los pacientes reciban una atención médica de calidad, y que se les trate con dignidad y respeto. En diciembre del año 2022 el Consejo General de Colegios Oficiales de Médicos de España publicó una nueva versión del Código de Deontología Médica español que pretende, entre otros fines, normativizar una asistencia médica de calidad científica y humana. Práctica médica sustentada en medicina con base científica, lex artis médica, seguridad del paciente, responsabilidad profesional, honestidad e integridad son algunos de los aspectos que en este documento actualizado de deontología médica enmarcan y define el quehacer del médico para un desempeño de medicina con calidad (AU)

Medical practice has two main dimensions, one scientific and the other human, and in both, the com mitment of the doctor is essential. Medical deontology, as a branch of ethics that deals with the duties and obligations of doctors, embodies in the codes of deontology the ethical principles and standards of mandatory compliance. From this point, medical practice should guarantee that patients receive an quality medical care, and to be treated with dignity and respect. In December 2022, the General Council of Official Medical Associations of Spain published a new version of the Spanish Code of Medical Ethics that aims, among other purposes, to standardize medical care of scientific and human quality. Medical practice sup ported by scientifically-based medicine, lex artis médica, patient safety, professional responsibility, honesty and integrity are some of the aspects that in this updated document of medical ethics frame and define the work of the doctor for a performance of medicine with quality (AU)

[Problems and thoughts in clinical safety evaluation of traditional Chinese medicine].

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.

Procoagulant Activity of Umbilical Cord-Derived Mesenchymal Stromal Cells' Extracellular Vesicles (MSC-EVs).

Many cell types, including cancer cells, release tissue factor (TF)-exposing extracellular vesicles (EVs). It is unknown whether MSC-EVs pose a thromboembolism risk due to TF expression. Knowing that MSCs express TF and are procoagulant, we hypothesize that MSC-EVs also might. Here, we examined the expression of TF and the procoagulant activity of MSC-EVs and the impact of EV isolation methods and cell culture expansion on EV yield, characterization, and potential risk using a design of experiments methodology. MSC-EVs were found to express TF and have procoagulant activity. Thus, when MSC-derived EVs are employed as a therapeutic agent, one might consider TF, procoagulant activity, and thromboembolism risk and take steps to prevent them.

[Evaluation of clinical safety and diagnostic efficacy of domestic liver-specific magnetic resonance contrast agent (gadoxetate disodium)].

Objective: To evaluate the clinical safety and diagnostic efficacy of domestic gadoxetate disodium (GdEOBDTPA). Methods: The imaging data from patients with space-occupying liver lesions who underwent GdEOBDTPA enhanced magnetic resonance examination at West China Hospital of Sichuan University between January 2020 and September 2020 were analyzed retrospectively. Clinical indicators were evaluated by the incidental condition of transient severe respiratory motion artifacts (TSM) in the arterial phase to assess the safety profile.The differences in quantitative and qualitative indicators for the risk factors of TSM in the arterial phase between the TSM group and the non-TSM group were compared by t-test and χ2 test. Observational indicators of the accuracy of diagnostic procedures: The 2018 version of the Liver Imaging Reporting and Data System (LI-RADS) was used to evaluate the main signs, auxiliary signs, and LR grades of lesions. Postoperative pathological findings were used as the gold standard for evaluating and diagnosing hepatocellular carcinoma (HCC). Simultaneously, the relative enhancement degree of the liver, the contrast between the lesion and the liver, and the cholangiography in the hepatobiliary phase were evaluated. The McNemar test was used to compare the differences in the diagnostic efficiency of physician 1 and physician 2 in the diagnosis of hepatocellular carcinoma according to the 2018 version of LI-RADS. Results: A total of 114 cases were included in this study. The incidence rate of TSM was 9.6% (11/114). Age [(53.8 ± 11.3) years vs. (55.4 ± 15.4) years, t = 0.465, P = 0.497], body weight [(65.8 ± 11.1) kg vs. (60.8 ± 7.6) kg, t = 1.468, P = 0.228], body mass index [(23.9 ± 3.1) kg/m(2) vs. (23.4 ± 3.0) kg/m(2), t = 0.171, P = 0.680], liver cirrhosis ratio (39 cases vs. 4 cases, χ (2) =1.776, P = 0.183), proportion of mild to moderate pleural effusion (32 cases vs. 4 cases, χ (2) = 0.000, P = 0.986), and proportion of mild to moderate ascites (47 cases vs. 5 cases χ (2) = 0.000, P = 0.991) had no statistically significant difference between the groups of non-TSM and TSM patients. According to the 2018 version of LI-RADS for the LR5 category, there was no statistically significant difference between the two physicians' HCC diagnoses in terms of sensitivity (91.4% vs.86.4%, χ (2) = 1.500, P = 0.219), specificity (72.7 % vs. 69.7%, χ (2) = 0.000, P = 1.000), positive predictive value (89.2% vs. 87.5%, χ (2) = 2.250, P = 0.125), negative predictive value (77.4% vs. 67.6%, χ (2) = 2.250, P = 0.125), and accuracy (86.0% vs. 81.6%, χ (2) = 0.131, P = 0.125). According to physicians 1 and 2 film review results, 91.2% (104/114) and 89.5% (102/114) of the contrast agent were discharged into the common bile duct or duodenum, respectively. In addition, 86.0% (98/114) of the patients had good liver enhancement, and 91.2% (104/114) of the lesions showed low signals relative to the liver background. Conclusion: Domestic gadoxetate disodium has a good clinical safety profile and diagnostic efficacy.

Advances in the phytochemical screening and biological potential of propolis.

Propolis is a natural resinous product collected from different parts of plants by bees and mixed with their salivary secretions. The occurrence of more than 180 different chemotypes has flavonoids, phenolic acids, esters, and phenolic aldehydes, as well as balsamic resins, beeswax, pollen, and essential and aromatic oils, among others. Its biological potential documented throughout the world justifies the need, from time to time, to organize reviews on the subject, with the intention of gathering and informing about the update on propolis. In this review (CRD42020212971), phytochemical advances, in vitro, in vivo, and clinical biological assays of pharmacological interest are showcased. The focus of this work is to present propolis clinical safety assays, antitumor, analgesic, antioxidant, anti-inflammatory, and antimicrobial activities. This literature review highlights propolis' promising biological activity, as it also suggests that studies associating propolis with nanotechnology should be further explored for enhanced bioprocessing applications.