Objective:To analyze the international status and level of clinical trial quality in China, and explore the advantages and value of scientific regulation of clinical research quality in China.Methods:The data is sourced from the relevant reports publicly released by the National Medical Products Administration (NMPA), the inspection reports and announcements published by the Center for Food and Drug Inspection of the NMPA, the inspection data displayed on the official website of the U.S. Food and Drug Administration (FDA), as well as clinical diagnosis and treatment guidelines issued by the National Comprehensive Cancer Network (NCCN) of United States and the Chinese Society of Clinical Oncology (CSCO) (data as of July 21, 2023). This data provides an analysis of the regulatory status of the implementation of clinical drug trials in China, inspection data, and the approval and market entry of new oncology drugs and feedback from their practical application.Results:The clinical trial quality inspection systems of China and the United States are generally aligned, with similar inspection subjects, focus areas, and public disclosure pathways. However, each has its characteristics in terms of inspection targets and types. The quality of clinical trial data in China has been continuously improving. Between 2009-2015 and 2016-July 2023, China underwent 25 and 20 FDA Bioresearch Monitoring (BIMO) inspections, respectively. The inspection results showing "No Action Indicated" (NAI) improved from 48.0% to 85.0%, while "Voluntary Action Indicated" (VAI) decreased from 44.0% to 15.0%. Official Action Indicated (OAI) measures were required in 2009 and 2012. Compared to the 2009-2015 period, there has been a clear upward trend in the quality of clinical trial data since 2016. From 2016 to July 2023, the number of new oncology drugs developed by Chinese pharmaceutical companies and included in professional guidelines has steadily increased. Specifically, 37 drugs (58.7%) were included in the 2022 edition of the CSCO guidelines, and 15 drugs (23.8%) were included in the 2023 edition of the NCCN guidelines, with 10 of these drugs featured in both guidelines.Conclusions:The implementation quality of clinical trials in China has gained a certain level of international recognition and competitiveness. This progress is attributed to national macro-level guidance, a unique institutional model, and clinical practices aligned with international standards. In the future, it will be necessary to further strengthen the scientific regulatory system and enhance clinical research capabilities to continue advancing the high-quality development of clinical trials.

Objective:To analyze the international status and level of clinical trial quality in China, and explore the advantages and value of scientific regulation of clinical research quality in China.Methods:The data is sourced from the relevant reports publicly released by the National Medical Products Administration (NMPA), the inspection reports and announcements published by the Center for Food and Drug Inspection of the NMPA, the inspection data displayed on the official website of the U.S. Food and Drug Administration (FDA), as well as clinical diagnosis and treatment guidelines issued by the National Comprehensive Cancer Network (NCCN) of United States and the Chinese Society of Clinical Oncology (CSCO) (data as of July 21, 2023). This data provides an analysis of the regulatory status of the implementation of clinical drug trials in China, inspection data, and the approval and market entry of new oncology drugs and feedback from their practical application.Results:The clinical trial quality inspection systems of China and the United States are generally aligned, with similar inspection subjects, focus areas, and public disclosure pathways. However, each has its characteristics in terms of inspection targets and types. The quality of clinical trial data in China has been continuously improving. Between 2009-2015 and 2016-July 2023, China underwent 25 and 20 FDA Bioresearch Monitoring (BIMO) inspections, respectively. The inspection results showing "No Action Indicated" (NAI) improved from 48.0% to 85.0%, while "Voluntary Action Indicated" (VAI) decreased from 44.0% to 15.0%. Official Action Indicated (OAI) measures were required in 2009 and 2012. Compared to the 2009-2015 period, there has been a clear upward trend in the quality of clinical trial data since 2016. From 2016 to July 2023, the number of new oncology drugs developed by Chinese pharmaceutical companies and included in professional guidelines has steadily increased. Specifically, 37 drugs (58.7%) were included in the 2022 edition of the CSCO guidelines, and 15 drugs (23.8%) were included in the 2023 edition of the NCCN guidelines, with 10 of these drugs featured in both guidelines.Conclusions:The implementation quality of clinical trials in China has gained a certain level of international recognition and competitiveness. This progress is attributed to national macro-level guidance, a unique institutional model, and clinical practices aligned with international standards. In the future, it will be necessary to further strengthen the scientific regulatory system and enhance clinical research capabilities to continue advancing the high-quality development of clinical trials.

Objective·To systematically review the effectiveness of actigraphy on the evaluation of circadian rhythm characteristics in patients with depression.Methods·A systematic literature search was conducted in PubMed,Embase,Web of Science,Cochrane Library,PsycINFO,CNKI,WanFang Data,and Chinese biomedical literature database(CBM),from the inception of each database to May 5th,2023.Case control studies that used actigraphy to evaluate circadian rhythms in patients with depression and compared them with healthy controls were collected.Literature was screened according to the inclusion and exclusion criteria,and the quality of the included literature was evaluated by using the Newcastle-Ottawa Scale.The meta-analysis was performed by using RevMan 5.4 software.Results·A total of 9 articles were included,including 390 patients with depression and 288 healthy controls.The meta-analysis showed that the MESOR(midline statistic of rhythm)(SMD=-0.29,95%CI-0.51 ?-0.07,P=0.009)of the circadian cosine function in patients with depression was lower than that in healthy controls;sleep onset(MD=33.06,95%CI 14.90 ? 51.23,P=0.000)and sleep offset(MD=53.80,95%CI 22.38 ? 85.23,P=0.000)were later in patients with depression than those in healthy controls;no statistical difference was found in the activity level of the most active 10 hours(SMD=-0.26,95%CI-0.52 ? 0.01,P=0.060)between patients with depression and healthy controls,although there was a trend for lower activity in patients with depression;no statistical difference was found in the acrophase(MD=25.33,95%CI-12.41 ? 63.06,P=0.190)of the circadian cosine function between patients with depression and healthy controls;no clear statistical significance of the difference was found in the amplitude(SMD=-0.14,95%CI-0.42 ? 0.14,P=0.340)and the activity level of the least active 5 hours(SMD=0.31,95%CI-0.10 ? 0.71,P=0.140)between patients with depression and healthy controls.Conclusion·Actigraphy can reflect circadian rhythm disruption in patients with depression to some extent,but the limited number of included studies and inconsistencies in the study populations and methodologies have affected the quality and results of the analyses.More high-quality clinical trials are needed to provide evidence.

The anterior disc displacement (ADD) leads to temporomandibular joint osteoarthritis (TMJOA) and mandibular growth retardation in adolescents. To investigate the potential functional role of fibrocartilage stem cells (FCSCs) during the process, a surgical ADD-TMJOA mouse model was established. From 1 week after model generation, ADD mice exhibited aggravated mandibular growth retardation with osteoarthritis (OA)-like joint cartilage degeneration, manifesting with impaired chondrogenic differentiation and loss of subchondral bone homeostasis. Lineage tracing using Gli1-CreER⁺; Tm^fl/-mice and Sox9-CreER⁺;Tm^fl/-mice showed that ADD interfered with the chondrogenic capacity of Gli1⁺ FCSCs as well as osteogenic differentiation of Sox9⁺ lineage, mainly in the middle zone of TMJ cartilage. Then, a surgically induced disc reposition (DR) mouse model was generated. The inhibited FCSCs capacity was significantly alleviated by DR treatment in ADD mice. And both the ADD mice and adolescent ADD patients had significantly relieved OA phenotype and improved condylar growth after DR treatment. In conclusion, ADD-TMJOA leads to impaired chondrogenic progenitor capacity and osteogenesis differentiation of FCSCs lineage, resulting in cartilage degeneration and loss of subchondral bone homeostasis, finally causing TMJ growth retardation. DR at an early stage could significantly alleviate cartilage degeneration and restore TMJ cartilage growth potential.
Animals ; Mice ; Osteogenesis ; Zinc Finger Protein GLI1 ; Fibrocartilage ; Temporomandibular Joint ; Disease Models, Animal ; Osteoarthritis ; Stem Cells ; Growth Disorders

Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. In this study, we aimed to develop and validate a model of oxidative stress injury for predicting BD. Data were collected from 1252 BD and 1359 MDD patients, including 64 MDD patients identified as converting to BD from 2009 through 2018. 30 variables from a randomly-selected subsample of 1827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, and prealbumin), sex hormones, cytokines, thyroid and liver function, and glycolipid metabolism. Univariate analyses and the Least Absolute Shrinkage and Selection Operator were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct a model for predicting bipolar disorder by oxidative stress biomarkers (BIOS) on a nomogram. Internal validation was assessed in the remaining 784 patients (30%), and independent external validation was done with data from 3797 matched patients from five other hospitals in China. 10 predictors, mainly oxidative stress markers, were shown on the nomogram. The BIOS model showed good discrimination in the training sample, with an AUC of 75.1% (95% CI: 72.9%-77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was good both in internal validation (AUC 72.1%, 68.6%-75.6%) and external validation (AUC 65.7%, 63.9%-67.5%). In this study, we developed a nomogram centered on oxidative stress injury, which could help in the individualized prediction of BD. For better real-world practice, a set of measurements, especially on oxidative stress markers, should be emphasized using big data in psychiatry.
Biomarkers/metabolism* ; Bipolar Disorder/metabolism* ; Depressive Disorder, Major/diagnosis* ; Early Diagnosis ; Humans ; Oxidative Stress

Classic hypothalamic-pituitary-end-organ feedback loops – the hypothalamic-pituitary-adrenal axis (HPAA), hypothalamic-pituitary-thyroidal axis (HPTA), and hypothalamic-pituitary-gonadal axis (HPGA) – are associated with the neuroendocrine and immune systems in major depressive disorder (MDD). Female patients with MDD present with evident neuroendocrine and immunological changes. Glucocorticoid, thyroid hormone, and reproductive steroid levels fluctuate with menstrual cycles, which might lead to glucocorticoid receptor resistance, impairment of triiodothyronine conversion, and sex hormone secretion disorders. In this review, we summarize the independent and interactive functions of these three axes in female MDD patients. The similar molecular structure of steroids implies an interrelationship between the hypothalamic-pituitary-end-organ axes and the competitive inhibitory effects at the receptor level, especially when considering the HPAA and HPGA.

Major depressive disorder (MDD), also referred to as depression, is one of the most common psychiatric disorders with a high economic burden. The etiology of depression is still not clear, but it is generally believed that MDD is a multifactorial disease caused by the interaction of social, psychological, and biological aspects. Therefore, there is no exact pathological theory that can independently explain its pathogenesis, involving genetics, neurobiology, and neuroimaging. At present, there are many treatment measures for patients with depression, including drug therapy, psychotherapy, and neuromodulation technology. In recent years, great progress has been made in the development of new antidepressants, some of which have been applied in the clinic. This article mainly reviews the research progress, pathogenesis, and treatment of MDD.

A correction to this paper has been published: https://doi.org/10.1007/s12264-021-00694-9.

Orthodontic resident training has a long history abroad. Its purpose is to teach general practitioners in dentistry about basic knowledge and operating standards and to lay a solid foundation for the normalization and standardization of techniques. Osaka Dental University, established in 1911, is one of the oldest dental higher education facilities in Japan and Asia. Its systematic orthodontic resident training program has specific characteristics, including a thorough foundation in basic training, sufficient practice time in clinical work, and an emphasis on both clinical thinking ability and technical detail mastery. Recently, orthodontic resident training programs in China have achieved significant progress in a short period. In this manuscript, we introduce the orthodontic training program of Osaka Dental University in terms of enrollment, training arrangements, orthodontic basic education and clinical training in order to offer a reference for the continuous improvement of the standardized training system for resident doctors of stomatology in China.