ObjectiveTo characterize the changes in the overall chemical profile and key index components during nine-time repeating steaming and sun-drying processing of Rhei Radix et Rhizoma， and to reveal the change law of its material basis. MethodsHigh performance liquid chromatography（HPLC） was used to analyze the changes in the overall chemical profile of Rhei Radix et Rhizoma decoction pieces， and the contents of 15 main active components such as chrysophanol-8-O-β-D-glucoside， chrysophanol and gallic acid in the process of nine-time repeating steaming and sun-drying were determined. Combined with chemometrics， the contents and quantity ratio relationships of the glycosides， aglycones and tannins during the processing of Rhei Radix et Rhizoma were analyzed， and the partial least squares-discriminant analysis（PLS-DA） and cluster analysis of the main components in different steaming times were conducted， the statistically significant differential markers were selected with the variable importance in the projection（VIP） value>1. ResultsIn the nine-time repeating steaming and sun-drying process of Rhei Radix et Rhizoma， there were certain regularity in the number and peak area of characteristic peaks and the steaming and sun-drying times， the anthraquinone glycosides and aglycones could be roughly divided into three stages， including rapid change stage， fluctuation change stage and stable stage， and the total amount of tannins showed a decreasing trend. However， the ratios between the three components mentioned above tended to stabilize after five rounds of steaming and sun-drying. The results of PLS-DA and cluster heatmap showed that the content of each component in Rhei Radix et Rhizoma fluctuated greatly during the 1-4 steaming and sun-drying processes， while the content of each component was relatively close during the 5-9 steaming and sun-drying processes. After screening， it was found that chrysophanol， emodin， chrysophanol-8-O-β-D-glucoside， rhein， physcion and emodin-8-O-β-D-glucoside could be used as the index components for distinguishing the processed products of Rhei Radix et Rhizoma with different steaming and sun-drying times. ConclusionThe changes in the properties and efficacy of Rhei Radix et Rhizoma caused by the processing of nine-time repeating steaming and sun-drying are due to the changes in the composition and ratio of various glycosides and complex tannins in this herb， which is also the key to the formation of its characteristic of "purgation with supplement". This study can provide a basis for the research on the processing mechanism of Rhei Radix et Rhizoma and the establishment of processing specifications.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

Objective:To study the experience and efficacy of treating the isolated left vertebral artery (ILVA) during total aortic arch replacement combined with stent-trunk surgery in patients with Stanford type A aortic dissection (TAAD) combined with ILVA.Methods:The clinical data of 21 patients with TAAD combined with ILVA from July 2017 to March 2022 in the First Affiliated Hospital of University of Science and Technology of China were retrospectively analyzed. All patients were treated with ILVA-left common carotid artery transplantation and total arch replacement combined with stent-trunk surgery under moderate hypothermia cardiopulmonary bypass and selective cerebral perfusion (SCP). Among them, aortic root repair surgery was in 15 cases, Bentall surgery in 6 cases, coronary artery bypass grafting performed simultaneously in 2 cases. The surgical details, postoperative complications and length of stay were recorded. The patients were followed up 1 and 12 months after surgery for CTA examination to observe the patency of transplanted ILVA. The follow-up was performed until October 1, 2022, and survival, aorta-related death and ILVA patency rate were recorded.Results:Three hundred and thirty-five TAAD patients were admitted during the same period, including 21 (6.27%) with ILVA. ILVA was reconstructed successfully in all patients. No complications related to ILVA were observed. Three cases died during the perioperative period: 1 case had preoperative myocardial infarction due to coronary artery involvement and the CPB could not be removed after operation; 1 case died of postoperative liver and renal failure due to severe organ hypoperfusion; 1 case suffered from postoperative acute renal failure and died of low cardiac output. The patients did not experience damage to the vagus nerve or recurrent laryngeal nerve, lymphatic leakage, chylothorax, ILVA thrombosis, paraplegia or cerebral vascular complications. The other 18 patients recovered and discharged from hospital. The median duration of follow-up was 30 (6 to 62) months. During the follow-up, aortic-related death did not observe, ILVA was unobstructed, and there were no manifestations of anastomotic stenosis or arterial stenosis.Conclusions:ILVA is a supra-aortic trunk variant, it is not so rare. ILVA may pose additional difficulties during total arch replacement surgery. The clinical effect of prior reconstruction of ILVA by ILVA-LCCA transposition is satisfactory, and it may be a simple and efficient method to complete reconstruction and optimize arch surgery before cardiopulmonary bypass.

Objective It analyzes the equity of pharmacists'allocation in China's healthcare organizations from 2012 to 2021,in order to provide reference for improving the service accessibility of pharmacists.Methods Based on the degree of agglomeration,analyzing the current situation and changing trend of pharmacists'allocation in healthcare organizations among different areas and provinces.Results The current allocation of pharmacists in China's healthcare organizations has not met the requirements.The situation in the eastern economically developed areas is better than that in other areas of the country either by geography or by population.While the western areas are large and sparsely populated,so the accessibility of pharmacist service is poor based on geographical allocation,but the equity is good based on population allocation.In the central area,the accessibility of pharmacist service is better when the allocation is based on geographical,but the equity is worse when the allocation is based on population.Conclusion China should further enrich the team of pharmacists in healthcare organizations to promote the coordinated development of different provinces.Furthermore,it also helps to promote the equity of pharmacists'allocation in China's healthcare organizations.

Objective It analyzes the equity of pharmacists'allocation in China's healthcare organizations from 2012 to 2021,in order to provide reference for improving the service accessibility of pharmacists.Methods Based on the degree of agglomeration,analyzing the current situation and changing trend of pharmacists'allocation in healthcare organizations among different areas and provinces.Results The current allocation of pharmacists in China's healthcare organizations has not met the requirements.The situation in the eastern economically developed areas is better than that in other areas of the country either by geography or by population.While the western areas are large and sparsely populated,so the accessibility of pharmacist service is poor based on geographical allocation,but the equity is good based on population allocation.In the central area,the accessibility of pharmacist service is better when the allocation is based on geographical,but the equity is worse when the allocation is based on population.Conclusion China should further enrich the team of pharmacists in healthcare organizations to promote the coordinated development of different provinces.Furthermore,it also helps to promote the equity of pharmacists'allocation in China's healthcare organizations.

Objective It analyzes the equity of pharmacists'allocation in China's healthcare organizations from 2012 to 2021,in order to provide reference for improving the service accessibility of pharmacists.Methods Based on the degree of agglomeration,analyzing the current situation and changing trend of pharmacists'allocation in healthcare organizations among different areas and provinces.Results The current allocation of pharmacists in China's healthcare organizations has not met the requirements.The situation in the eastern economically developed areas is better than that in other areas of the country either by geography or by population.While the western areas are large and sparsely populated,so the accessibility of pharmacist service is poor based on geographical allocation,but the equity is good based on population allocation.In the central area,the accessibility of pharmacist service is better when the allocation is based on geographical,but the equity is worse when the allocation is based on population.Conclusion China should further enrich the team of pharmacists in healthcare organizations to promote the coordinated development of different provinces.Furthermore,it also helps to promote the equity of pharmacists'allocation in China's healthcare organizations.

Objective It analyzes the equity of pharmacists'allocation in China's healthcare organizations from 2012 to 2021,in order to provide reference for improving the service accessibility of pharmacists.Methods Based on the degree of agglomeration,analyzing the current situation and changing trend of pharmacists'allocation in healthcare organizations among different areas and provinces.Results The current allocation of pharmacists in China's healthcare organizations has not met the requirements.The situation in the eastern economically developed areas is better than that in other areas of the country either by geography or by population.While the western areas are large and sparsely populated,so the accessibility of pharmacist service is poor based on geographical allocation,but the equity is good based on population allocation.In the central area,the accessibility of pharmacist service is better when the allocation is based on geographical,but the equity is worse when the allocation is based on population.Conclusion China should further enrich the team of pharmacists in healthcare organizations to promote the coordinated development of different provinces.Furthermore,it also helps to promote the equity of pharmacists'allocation in China's healthcare organizations.

Objective It analyzes the equity of pharmacists'allocation in China's healthcare organizations from 2012 to 2021,in order to provide reference for improving the service accessibility of pharmacists.Methods Based on the degree of agglomeration,analyzing the current situation and changing trend of pharmacists'allocation in healthcare organizations among different areas and provinces.Results The current allocation of pharmacists in China's healthcare organizations has not met the requirements.The situation in the eastern economically developed areas is better than that in other areas of the country either by geography or by population.While the western areas are large and sparsely populated,so the accessibility of pharmacist service is poor based on geographical allocation,but the equity is good based on population allocation.In the central area,the accessibility of pharmacist service is better when the allocation is based on geographical,but the equity is worse when the allocation is based on population.Conclusion China should further enrich the team of pharmacists in healthcare organizations to promote the coordinated development of different provinces.Furthermore,it also helps to promote the equity of pharmacists'allocation in China's healthcare organizations.

Objective It analyzes the equity of pharmacists'allocation in China's healthcare organizations from 2012 to 2021,in order to provide reference for improving the service accessibility of pharmacists.Methods Based on the degree of agglomeration,analyzing the current situation and changing trend of pharmacists'allocation in healthcare organizations among different areas and provinces.Results The current allocation of pharmacists in China's healthcare organizations has not met the requirements.The situation in the eastern economically developed areas is better than that in other areas of the country either by geography or by population.While the western areas are large and sparsely populated,so the accessibility of pharmacist service is poor based on geographical allocation,but the equity is good based on population allocation.In the central area,the accessibility of pharmacist service is better when the allocation is based on geographical,but the equity is worse when the allocation is based on population.Conclusion China should further enrich the team of pharmacists in healthcare organizations to promote the coordinated development of different provinces.Furthermore,it also helps to promote the equity of pharmacists'allocation in China's healthcare organizations.