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Modern medicine has made remarkable achievements in safeguarding people's life and health, however, it is increasingly found that in the face of complex diseases, selective targeting of single target is often difficult to produce a comprehensive rehabilitation effect, and is prone to induce drug resistance, toxic side effects. Traditional Chinese medicine (TCM) has a long history of clinical application, and its clinical value in the treatment of complex diseases such as cardiovascular and cerebrovascular diseases, digestive diseases, skin diseases, rheumatism and immunity diseases, and adjuvant treatment of tumors has been proven to have obvious advantages. However, its modern research is relatively lagging behind, and in the face of the aging society and the characteristics of the modern disease spectrum, the traditional knowledge-driven research paradigm seems to be stuck in a bottleneck and difficult to make greater breakthroughs. Focusing on the key issues of TCM development in the new era, the clinical value-oriented strategy becomes to be a new research paradigm of TCM inheritance and innovation development, and dominant diseases would be the focus of the TCM inheritance and innovation development, which has been highly valued in recent years by the TCM academia and the relevant national management departments. Based on the clinical value, a series of policies are formulated for the selection and evaluation of the TCM dominant diseases (TCMDD), and exploratory researches about the clinical efficacy characteristics, the modern scientific connotation interpretation were carried out. The clinical value-oriented research paradigm of TCMDD inheritance and innovation development has been initially formed, which is characterized by strong policy support as the guarantee, systematic and standardized selection and evaluation methods as the driving force, scientific and effective research on internal mechanisms as the expansion, and effective clinical guidelines and principles as the transformation, which is of great value in promoting the high-quality development of the industries and undertaking of TCM. In this paper, the main policy support, selection and evaluation methods, therapeutic effect characterization, and modern scientific connotation research strategies of TCMDD in recent years have been comprehensively sorted out, with a view to providing the healthy and benign development of the research on TCMDD.
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Ischemic stroke (IS) is a severe cerebrovascular disease with a high incidence, mortality, and disability rate. The first-line treatment for IS is the use of recombinant tissue plasminogen activator (r-tPA). Regrettably, numerous patients encounter delays in treatment due to the narrow therapeutic window and the associated risk of hemorrhage. Traditional Chinese medicine (TCM) has exhibited distinct advantages in preventing and treating IS. TCM enhances cerebral microcirculation, alleviates neurological disorders, regulates energy metabolism, mitigates inflammation, reduces oxidative stress injuries, and inhibits apoptosis, thereby mitigating brain damage and preventing IS recurrence. This article summarizes the etiology, pathogenesis, therapeutic strategies, and relationship with modern biology of IS from the perspective of TCM, describes the advantages of TCM in the treatment of IS, and further reviews the pharmacodynamic characteristics and advantages of TCM in the acute and recovery phases of IS as well as in post-stroke complications. Additionally, it offers valuable insights and references for the clinical application of TCM in IS prevention and treatment, as well as for the development of novel drugs.
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Cognitive dysfunction is one of the common central nervous systems (CNS) complications of diabetes mellitus, which seriously affects the quality of life of patients and results in a huge economic burden. The glymphatic system dysfunction mediated by aquaporin-4 (AQP4) loss or redistribution in perivascular astrocyte endfeet plays a crucial role in diabetes-induced cognitive impairment (DCI). However, the mechanism of AQP4 loss or redistribution in the diabetic states remains unclear. Accumulating evidence suggests that peripheral insulin resistance target tissues and CNS communication affect brain homeostasis and that exosomal miRNAs are key mediators. Glucose and lipid metabolism disorder is an important pathological feature of diabetes mellitus, and skeletal muscle, liver and adipose tissue are the key target insulin resistance organs. In this review, the changes in exosomal miRNAs induced by peripheral metabolism disorders in diabetes mellitus were systematically reviewed. We focused on exosomal miRNAs that could induce low AQP4 expression and redistribution in perivascular astrocyte endfeet, which could provide an interorgan communication pathway to illustrate the pathogenesis of DCI. Furthermore, the mechanisms of exosome secretion from peripheral insulin resistance target tissue and absorption to the CNS were summarized, which will be beneficial for proposing novel and feasible strategies to optimize DCI prevention and/or treatment in diabetic patients.
RESUMO
BACKGROUND: Directly percutaneous injection of protein-denaturant hydrochloric acid (PDHA) into tumors can lead to fast killing of tumor, sustained drug release and prevention of in situ recurrence of tumor. However, whether implants can be used combined with denaturant still remains unknown. OBJECTIVE: To investigate the compatibility of fluorouracil implants and PDHA (6 mol/L). DESIGN, TIME AND SETTING: Observational study was performed in the Hefei Industry University between October 2006 and March 2007. MATERIALS: A total of 78 Wistar rats, weighing (200i20) g, half males and half females, were used for testing drug release in vivo. Drugs fluorouracil implants (H20030345; columniform particle, diameter 0.8 mm, length 4 mm; specifications: Fluorouracil 2 mg/particle; batch number: 20060922; meeting the National Drug Quality Standards [WS1-(X-103)-2005Z]) were provided by Wuhu Zhongren Pharmaceutical Company,Ltd. Hydrochloric acid (37%) was analytical reagent. METHODS: 96 tubes of the implants and PDHA were kept at (37.0± 0.5) ℃. Each time, six samples were collected at 1, 8, 16, 24, 96, 120, 168, 240, 360, 432, 480, 528, 600, 720, and 960 hours after incubation. Appearance of the implants was observed by microscope. Stability of fluorouracil in PDHA was determined by HPLC and ultraviolet absorb method. Based on the entering quantity and residual quantity of fluorouracil, the release rates were calculated. MAIN OUTCOME MEASURES: The approximate solubility, stability and morphological change of fluorouracil in denaturant and the corresponding drug release character in both denaturant and rats in vivo. RESULTS: At (37.0±0,5) ℃, the fluorouracil was stable for 960 hours in PDHA, the saturated concentration of fluorouracil was (22.72±0.04) g/L. The appearance of implants was intact. The surface was porous. Compared with the speed of releasing drug in rats, the speed of releasing drug was faster in the early stage of release process and slower in the later stage. The drug release was incomplete. At 1, 24, 96, 360 and 960 hours, the implants' release rates were (11.9±6.7)%, (37.9±5.3)%, (52.6±4.5)%, (75.3±3.8)%, and (85.5±2.1)%, respectively. CONCLUSION: The fluorouracil implants and hydrochloric acid (6 mol/L) are compatible and no influence is detected during the observation.