OBJECTIVE To clarify the roles and functions of full-time pharmacists in the management of early-phase clinical trials of antineoplastic drugs， and to provide theoretical and practical support for their transformation from traditional drug managers to multi-dimensional roles in clinical research. METHODS Combined with relevant regulations such as the Good Clinical Practice （GCP） （2020 Edition）， and based on the clinical practice experience of the Phase Ⅰ Clinical Ward in our hospital， this study systematically sorted out full-time pharmacists’ roles and functions in early-phase clinical trials of antineoplastic drugs， and explored the core challenges and optimization pathways for role transformation and capacity-building of domestic full-time clinical trial pharmacists. RESULTS & CONCLUSIONS Full-time pharmacists assumed multiple roles in early-phase clinical trials of antineoplastic drugs， including providing pharmaceutical support for protocol design， implementing whole-process standardized management of clinical trial drugs， ensuring medication safety for clinical trial subjects/participants， conducting quality control throughout the clinical trial process， and serving as a bridge for interdisciplinary collaboration and communication. Currently， there are challenges in this field in China， such as unclear roles， an imperfect capacity building system， and insufficient regulatory support. This paper proposes that by establishing a standardized role framework， clarifying the core responsibilities and authorities of full-time pharmacists， and leveraging cutting-edge technologies to provide comprehensive support for their roles， so as to fully harness their pharmaceutical expertise and contribute to the standardization and efficiency of the antineoplastic new drug development process.

By analyzing the current application of multi-modal data in the diagnosis of gastric "inflammation-cancer" transformation， this study explored the feasibility and strategies for constructing a disease-syndrome integrated diagnosis and treatment system. Based on traditional Chinese medicine （TCM） phenomics， we proposed utilizing multi-modal data from literature research， cross-sectional studies， and cohort follow-ups， combined with artificial intelligence technology， to establish a multi-dimensional diagnostic and treatment index system. This approach aims to uncover the complex pathogenesis and transformation patterns of gastric "inflammation-cancer" progression. Additionally， by dynamically collecting TCM four-diagnostic information and modern medical diagnostic information through a long-term follow-up system， we developed three major modules including information extraction， multi-modal phenotypic modeling， and information output， to make it enable real-world clinical data-driven long-term follow-up and treatment of chronic atrophic gastritis. This system can provide technical support for clinical diagnosis， treatment evaluation， and research， while also offering insights and methods for intelligent TCM diagnosis.

Phase Ⅰ clinical trials play a crucial role in the research and development of new drugs, serving as the initial studies to assess their safety, tolerability, effectiveness, and pharmacokinetic properties in humans. These trials involve uncertainties regarding safety and efficacy. Comprehensive management of all aspects of phase Ⅰ clinical trials for anti-tumor drugs is crucial to protect the rights and safety of participants. This article provides an in-depth analysis of the key points and precautions necessary for effective quality control throughout the process. The analysis is informed by guidelines such as the “Good Clinical Practice for Drugs” “Key Points and Judgment Principles for Drug Registration Verification” “Key Points and Judgment Principles for Supervision and Inspection of Drug Clinical Trial Institutions” and the standard operating procedures for quality control of the center. Topics discussed include informed consent, inclusion criteria, experimental drugs, biological samples, adverse events, and serious adverse events. The goal is to standardize quality control in phase Ⅰ clinical trials of anti-tumor drugs, ensure the authenticity and reliability of clinical trial data, and protect the rights and safety of participants.

BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*

BACKGROUND: Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV). METHODS: We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development. RESULTS: We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron. CONCLUSION Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Child ; Humans ; Neurodevelopmental Disorders/epidemiology* ; Genetic Testing ; Phenotype ; Brain/pathology* ; Genetic Background ; SOX Transcription Factors/genetics*

Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; Logistic Models ; Phenotype ; Risk Factors

Objective:To explore the latest progress of oncology drug clinical trials in China under COVID-19, as well as to provide decision-making evidence for related stakeholders. Research progress of oncology drug trials and approved cancer drugs in China in 2020 were systematically summarized and compared with 2019.Methods:Information Disclosure Platform for Drug Clinical Studies and China Food and Drug Administration Query System for Domestic and Imported Drug were searched for registered clinical trials and approved oncology drugs, respectively. The trial scope, stage, drug type, effect and mechanism of domestic and global pharmaceutical enterprises were compared between 2019 and 2020.Results:A total of 722 cancer drug trials registered in China in 2020, with an annual growth rate of 52.3%, accounting for 28.3% of all registered trials. Among them, 603 (83.5%) trials were initiated by domestic pharmaceutical enterprises, and 105 (14.5%) were international multicenter trials, phase I trials accounted for 44.5%. For all those trials, there were 458 cancer drug varieties, with an annual growth rate of 36.7%, and 361 (85.8%) were developed by domestic enterprises. Most of the investigational products were therapeutic innovative drugs (77.1%), major in tumor treatment (92.8%). In terms of mechanism, targeted drugs were the most popular, accounting for 76.6%, and programmed cell death-1 (PD-1) and epithelial growth factor receptor (EGFR) were the most common targets. In addition, there were 19 anticancer drugs from 17 companies approved in China in 2019, with 10 drugs from domestic companies. Lung cancer and breast cancer are the most common indications for both registered trials and marketed drugs. No statistically significant differences were found between 2020 and 2019 in terms of the distribution of trial sponsor, scope and stage, as well as the distribution of drug type, effect and mechanism ( P>0.05). Conclusions:During the Covid-19 epidemic period, clinical trials of oncology drugs in China progress smoothly and maintain a high growth rate. Series of innovative products obtained by domestic enterprises in 2020 is the main driving force of development of oncology drug clinical trials in China.

Objective:To explore the latest progress of oncology drug clinical trials in China under COVID-19, as well as to provide decision-making evidence for related stakeholders. Research progress of oncology drug trials and approved cancer drugs in China in 2020 were systematically summarized and compared with 2019.Methods:Information Disclosure Platform for Drug Clinical Studies and China Food and Drug Administration Query System for Domestic and Imported Drug were searched for registered clinical trials and approved oncology drugs, respectively. The trial scope, stage, drug type, effect and mechanism of domestic and global pharmaceutical enterprises were compared between 2019 and 2020.Results:A total of 722 cancer drug trials registered in China in 2020, with an annual growth rate of 52.3%, accounting for 28.3% of all registered trials. Among them, 603 (83.5%) trials were initiated by domestic pharmaceutical enterprises, and 105 (14.5%) were international multicenter trials, phase I trials accounted for 44.5%. For all those trials, there were 458 cancer drug varieties, with an annual growth rate of 36.7%, and 361 (85.8%) were developed by domestic enterprises. Most of the investigational products were therapeutic innovative drugs (77.1%), major in tumor treatment (92.8%). In terms of mechanism, targeted drugs were the most popular, accounting for 76.6%, and programmed cell death-1 (PD-1) and epithelial growth factor receptor (EGFR) were the most common targets. In addition, there were 19 anticancer drugs from 17 companies approved in China in 2019, with 10 drugs from domestic companies. Lung cancer and breast cancer are the most common indications for both registered trials and marketed drugs. No statistically significant differences were found between 2020 and 2019 in terms of the distribution of trial sponsor, scope and stage, as well as the distribution of drug type, effect and mechanism ( P>0.05). Conclusions:During the Covid-19 epidemic period, clinical trials of oncology drugs in China progress smoothly and maintain a high growth rate. Series of innovative products obtained by domestic enterprises in 2020 is the main driving force of development of oncology drug clinical trials in China.

Objective:To explore the feasibility of using Double FLASH coronary CTA (CCTA) to evaluate myocardial blood perfusion based on the original Patlak Plots.Methods:A total of 50 subjects with non-ischemic heart disease were prospectively included in the study who received dynamic myocardial CT perfusion (CTP) and Double FLASH CTA scans in General Hospital of Tianjin Medical University from January 2018 to January 2020 due to coronary heart disease or suspected coronary heart disease. The age of the enrolled patients was at least 18 years old and there was no moderate or above stenosis on CTA. The dynamic CTP images were analyzed by using CTP analysis software on FRONTIER platform to calculate the CTP derived MBF (MBF CTP). While the CTA derived MBF (MBF CTA) was calculated from the CT attenuation values of both aorta and myocardium segments on two scanning time set of Double FLASH CTA which were measured by two independent radiologists. Pearson correlation and Bland-Altman analysis were used to compare the results of MBF CTP and MBF CTA. Results:There was a strong linear correlation between MBF CTP and MBF CTA measurements. In the mid anteroseptal level: MBF CTA=0.936MBF CTP-11.999, r2=0.600, P<0.01. In the mid anterolateral level: MBF CTA=1.010MBF CTP-9.206, r2=0.448, P<0.01. In the apex: MBF CTA=0.822MBF CTP+16.904, r2=0.375, P<0.01. Bland-Altman analysis also showed there were no significant differences between MBF CTP and MBF CTA measurements. Compared with dynamic CTP scan, Double FLASH CTA mode significantly reduced the radiation dose [(4.33±1.89) mSv vs. (1.38±0.19) mSv, t=4.378, P=0.030]. Conclusions:This study validated the feasibility and accuracy of the MBF CTA measurement based on the theory of Patlak Plots only using Double FLASH CTA images. This method might have the potential to expand the clinical application of one-stop CTP examination for simultaneously evaluating coronary artery and myocardial ischemia in the clinic.

Objective:To deliver understanding of the latest research progress on clinical trials and approval of dermatological drugs in China in 2020.Methods:A registration and information disclosure platform for drug clinical studies and a query system for domestic and imported drugs in the National Medical Products Administration of China were searched for registered clinical trials and approved dermatological drugs, respectively. The number and stages of clinical trials, indications and classification of involved products, and listed dermatological drugs in 2020 were summarized and depicted.Results:There were 157 dermatological drug trials registered in China in 2020, accounting for 6.16% of all the 2 548 clinical drug trials, including 127 (80.9%) initiated by Chinese pharmaceutical enterprises and 25 (15.9%) international multicenter trials. Among the 127 drug trials initiated by Chinese pharmaceutical enterprises, bioequivalence trials were mostly common, accounting for 55.9% (71/127) . Compared with global pharmaceutical enterprises, domestic pharmaceutical companies initiated significantly decreased proportions of international multicenter trials (1.9% [3/157] vs. 14.0% [22/157], P < 0.001) , but significantly increased proportions of phaseⅠclinical trials and bioequivalence trials (24.4% [31/127] vs. 10.0% [3/30], 55.9% [71/127] vs. 0, respectively, both P < 0.001) . Totally, 90 kinds of dermatological drug were involved in all the trials, psoriasis, atopic dermatitis and melanoma were the most common indications, and innovative drugs accounted for 53.3% (48/90) ; the proportion of innovative drugs was significantly lower in domestic pharmaceutical companies than in global pharmaceutical companies (43.2% [32/74] vs. 16/16, P < 0.001) . In addition, 28 dermatological drugs developed by 22 pharmaceutical companies were approved in China in 2020, of which 21 drugs were developed by domestic pharmaceutical companies. Conclusion:Clinical drug trials carried out by domestic pharmaceutical companies mostly focus on generic drugs, and it is still necessary for domestic pharmaceutical companies to further improve the innovation ability.