Aim To investigate the effect of Xuefu Zhuyu decoction on transforming growth factor-β1(TGF-β1 ) -induced endothelial-to-mesenchymal transition (EndMT) of pulmonary microvascular endothelial cells ( PMVEC), and further analyze the mechanism related to the TGF-β1/Smad signaling pathway. Method To construct an EndMT cell model, PMVEC was treated with TGF-β1 (5 μg · L

We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC₅₀) and selectivity index (SI) values of 2.36 μmol·L^-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (K_D) value of 1.36 μmol·L^-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

Objective To investigate the relationship between the expression of long non-coding RNA HOXA-AS2(lncRNA HOXA-AS2),long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1),and long non-coding RNA CRNDE(lncRNA CRNDE)in endometrial carcinoma and the clinical pathological character-istics and prognosis of patients.Methods Collect samples of endometrial carcinoma cancer tissues and adja-cent tissues excised during surgery from 119 endometrial carcinoma patients admitted to a hospital from Octo-ber 2017 to February 2020.The relative expression levels of HOXA-AS2,FOXD2-AS1 and CRNDE in tissues were retrospectively analyzed,as well as their relationship with clinicopathological features and 3-year survival rate of patients.Results The relative expression levels of HOXA-AS2,FOXD2-AS1 and CRNDE in cancer tissues of endometrial carcinoma patients were higher than those in adjacent tissues,with statistical signifi-cance(P＜0.05).The relative expression levels of HOXA-AS2,FOXD2-AS1 and CRNDE in cancer tissues of endometrial carcinoma patients were positively correlated(rHOXA-As2 vs.FOXD2-AS1=0.384,P=0.001;rHoXA-AS2 vs.CRNDE=0.576,P＜0.001;rFoXD2-AS1 vs.CRNDE=0.326,P=0.003).In the HOXA-AS2,FOXD2-AS1 and CRNDE high expression group,the proportion of patients with international federation of gynecology and ob-stetrics(FIGO)stage Ⅲ+Ⅳ,lymph node metastasis,deep infiltration and low differentiation was higher than that in the low expression group,with statistical significance(P＜0.05).The 3-year survival rate of low HOXA-AS2 expression group in endometrial cancer patients(52/60,86.67％)was higher than that of high HOXA-AS2 expression group(40/59,67.79％),the difference was statistically significant(x2=6.039,P＜0.05).The 3-year survival rate of patients with endometrial cancer with low FOXD2-AS1 expression group(53/59,89.83％)was higher than that of patients with endometrial cancer with high FOXD2-AS1 expression group(39/60,65.00％),and the difference was statistically significant(x2=10.456,P＜0.05).The 3-year sur-vival rate of low CRNDE expression group in endometrial cancer patients(51/60,85.00％)was higher than that of high CRNDE expression group(41/59,69.49％),and the difference was statistically significant(x2=4.079,P＜0.05).HOXA-AS2,FOXD2-AS1,and CRNDE were risk factors for death in endometrial carcinoma patients(P＜0.05).Conclusion The expression of HOXA-AS2,FOXD2-AS1,and CRNDE in endometrial carcinoma cancer tissue is closely related to the clinical pathological characteristics and prognosis of patients.

ObjectiveExosomes are microvesicles which could be secreted by all cell types with diameters between 30 and 150 nm. It was widely distributed in body fluids including blood, urine, and breast milk. Exosomes are considered as potential biomarkers and drug carriers by reason of containing nucleic acids, lipids, proteins and other bioactive molecules. Milk-derived exosomes have been widely used as drug delivery carriers to treat targeted diseases with a lower cost, higher biocompatibility and lower immunogenicity. Until now, there is no research about the milk-derived exosomes phosphorylation to reveal the difference of protein phosphorylation in different species of milk. To investigate the pathways and proteins with specific functions, phosphorylated proteomic analysis of milk-derived exosomes from different species is performed, and provide new ideas for exploring diversified treatments of disease. MethodsWhey and exosomes derived from bovine, porcine and caprine milk were performed for proteomics and phosphoproteomics analysis. The relationship between milk exosome proteins from different species and signaling pathways were analyzed using bioinformatics tools. ResultsA total of 4 191 global proteins, 1 640 phosphoproteins and 4 064 phosphosites were identified from 3 species of milk-derived exosomes, and the exosome proteins and phosphoproteins from different species were significantly higher than those of whey. Meanwhile, some special pathways were enriched like Fcγ-mediated phagocytosis from bovine exosomes, pathways related with neural and immune system from caprine exosomes, positive and negative regulation of multiple activities from porcine exosomes. ConclusionIn this study, the proteomic and phosphoproteomic analyses of exosomes and whey from bovine, porcine and caprine milk were carried out to reveal the difference of composition and related signaling pathways of milk exosome from different species. These results provided powerful support for the application of exosomes from different milk sources in the field of disease treatment.

ObjectiveThe traditional Chinese medicine Strychnos nux-vomica L. (SN) has the clinical effect of reducing swelling and relieving pain; however, SN is toxic due to its alkaloid components. Little is known about the endogenous metabolic changes induced by SN toxicity in rats and their potential effects on the metabolic dysregulation of intestinal microbiota. Therefore, toxicological investigation of SN is of great significance to its safety assessment. In this study, the toxic mechanisms of SN were explored using a combination of metabonomics and 16S rRNA gene sequencing. MethodsThe toxic dose, intensity, and target organ of SN were determined in rats using acute, cumulative, and subacute toxicity tests. UHPLC-MS was used to analyze the serum, liver, and renal samples of rats after intragastric SN administration. The decision tree and K Nearest Neighbor (KNN) model were established based on the bootstrap aggregation (bagging) algorithm to classify the omics data. After samples were extracted from rat feces, the high-throughput sequencing platform was used to analyze the 16S rRNA V3-V4 region of bacteria. ResultsThe bagging algorithm improved the accuracy of sample classification. Twelve biomarkers were identified, where their metabolic dysregulation may be responsible for SN toxicity in vivo. Several types of bacteria such as Bacteroidetes, Anaerostipes, Oscillospira and Bilophila, were demonstrated to be closely related to physiological indices of renal and liver function, indicating that SN-induced liver and kidney damage may be related to the disturbance of these intestinal bacteria. ConclusionThe toxicity mechanism of SN was revealed in vivo, which provides a scientific basis for the safe and rational clinical use of SN.

Objective To explore the difference in efficacy of metoprolol versus ivabradine in the treatment of postural orthostatic tachycardia syndrome(POTS)in the elderly after COVID-19 infection.Methods A total of 110 patients diagnosed with POTS at our department from Decem-ber 1,2022 to January 31,2023 were included.According to their drug regimen,they were divided into metoprolol group(62 patients)and ivabradine group(48 patients).On the 28th day of out-patient follow-up,the resting heart rate,heart rate of 10 min of standing,symptom disappearance rate,hospitalization rate,and mortality rate were compared between the two groups.Results On the 28th day of treatment,the resting heart rate and postural heart rate for 10 min were decreased in both groups when compared with the levels at initial diagnosis(P＜0.01).And there were no significant differences in the two types of heart rate between the two groups on the 28th day(71.0±7.0 vs 72.1±7.0,P=0.401;76.5±7.2 vs 77.4±7.6,P=0.573).No obvious differences were observed between the two groups in symptom disappearance rate,hospitalization rate,or mortality rate(88.7％vs 89.6％,3.2％vs2.1％,0％vs 0％,P＞0.05).Conclusion Metoprolol and ivabradine can effectively treat POTS in the elderly patients after COVID-19 infection.

Objective:To develop a robotic digestive endoscope system (RDES) and to evaluate its feasibility, safety and control performance by experiments.Methods:The RDES was designed based on the master-slave control system, which consisted of 3 parts: the integrated endoscope, including a knob and button robotic control system integrated with a gastroscope; the robotic mechanical arm system, including the base and arm, as well as the endoscopic advance-retreat control device (force-feedback function was designed) and the endoscopic axial rotation control device; the control console, including a master manipulator and an image monitor. The operator sit far away from the endoscope and controlled the master manipulator to bend the end of the endoscope and to control advance, retract and rotation of the endoscope. The air supply, water supply, suction, figure fixing and motion scaling switching was realized by pressing buttons on the master manipulator. In the endoscopy experiments performed on live pigs, 5 physicians each were in the beginner and advanced groups. Each operator operated RDES and traditional endoscope (2 weeks interval) to perform porcine gastroscopy 6 times, comparing the examination time. In the experiment of endoscopic circle drawing on the inner wall of the simulated stomach model, each operator in the two groups operated RDES 1∶1 motion scaling, 5∶1 motion scaling and ordinary endoscope to complete endoscopic circle drawing 6 times, comparing the completion time, accuracy (i.e. trajectory deviation) and workload.Results:RDES was operated normally with good force feedback function. All porcine in vivo gastroscopies were successful, without mucosal injury, bleeding or perforation. In beginner and advanced groups, the examination time of both RDES and ordinary endoscopy tended to decrease as the number of operations increased, but the decrease in time was greater for operating RDES than for operating ordinary endoscope (beginner group P=0.033; advanced group P=0.023). In the beginner group, the operators operating RDES with 1∶1 motion scaling or 5∶1 motion scaling to complete endoscopic circle drawing had shorter completion time [1.68 (1.40, 2.17) min, 1.73 (1.47, 2.37) min VS 4.13 (2.27, 5.16) min, H=32.506, P<0.001], better trajectory deviation (0.50±0.11 mm, 0.46±0.11 mm VS 0.82±0.26 mm, F=38.999, P<0.001], and less workload [42.00 (30.00, 50.33) points, 43.33 (35.33, 54.00) points VS 52.67 (48.67, 63.33) points, H=20.056, P<0.001] than operating ordinary endoscope. In the advanced group, the operators operating RDES with 1∶1 or 5∶1 motion scaling to complete endoscopic circle drawing had longer completion time than operating ordinary endoscope [1.72 (1.37, 2.53) min, 1.57 (1.25, 2.58) min VS 1.15 (0.86, 1.58) min, H=13.233, P=0.001], but trajectory deviation [0.47 (0.13, 0.57) mm, 0.44 (0.39, 0.58) mm VS 0.52 (0.42, 0.59) mm, H=3.202, P=0.202] and workload (44.62±21.77 points, 41.24±12.57 points VS 44.71±17.92 points, F=0.369, P=0.693) were not different from those of the ordinary endoscope. Conclusion:The RDES enables remote control, greatly reducing the endoscopists' workload. Additionally, it gives full play to the cooperative motion function of the large and small endoscopic knobs, making the control more flexible. Finally, it increases motion scaling switching function to make the control of endoscope more flexible and more accurate. It is also easy for beginners to learn and master, and can shorten the training period. So it can provide the possibility of remote endoscopic control and fully automated robotic endoscope.

Objective The contents of 11 nucleosides and base components in 10 batches of samples from 5 provinces(cities)including Chongqing,Yunnan and Shaanxi were determined,and the differences in nucleosides and base components in Fritillaria taipaiensis were compared by chemometric analysis,and the quality was comprehensively evaluated,so as to provide a reference for the cultivation of excellent varieties and the selection of medicinal materials.Methods Nucleoside and base components were extracted from Fritillaria taipaiensis by ultrasonication in aqueous solutions,and the content of each component was determined by HPLC-DAD method.The origin was classified by principal component analysis(PCA)and hierarchical cluster analysis(HCA).Partial least squares discriminant analysis(PLS-DA)was used to determine the differentiated index components in Fritillaria taipaiensis.Then the differences in the contents of the index components among samples from different origins were compared.Results It was found that 11 nucleoside and base components differed significantly among different origins of Fritillaria taipaiensis.Principal component analysis and hierarchical cluster analysis indicated that all samples could be clustered into 4 categories.Five characteristic components,including uracil,cytosine,uridine,inosine,and adenosine,were identified by PLS-DA.The nucleosides and bases in samples from Chongqing and Hubei were relatively high,and the quality of the samples was comparatively superior.Conclusion This method is simple,reproducible,accurate and reliable.It has screened out the index nucleoside and base components in the identification of Fritillaria taipaiensis of different origins,which can be used to initially elucidate the differences of samples between different origins.Additionally,it can better reflect the quality of Fritillaria taipaiensis,and can provide reference for the selection of procurement origin and the quality control for Fritillaria taipaiensis.

OBJECTIVE To provide a reference for the implementation and high-quality development of hospital medication reconciliation. METHODS A semi-structured questionnaire was designed to investigate the implementation of drug reconciliation services in medical institutions before and after the release of 5 standards such as Standard for Medication Reconciliation Services in Medical Institutions（“standards” for short，in 2021 and 2022）. Descriptive statistical analysis was conducted on the survey results. RESULTS After the promulgation of the standards， the medication reconciliation service rate of all types of medical institutions increased from 15.10% （434/2 874） in 2021 to 27.84%（363/1 304） in 2022. In 2022， in the 363 medical institutions providing drug reconciliation services， the median number of pharmacists involved in drug reconciliation was 6. The participation rate of pharmacists in standardized training for drug reconciliation services was 75.00%， among which the participation rate of third-class hospitals was higher， reaching 85.71%. The main stages covered by medication reconciliation services included patient admission， transfer between departments， and discharge. The main problems found in the service included repeated medication （252， 69.42%）， inappropriate usage and dosage （228， 62.81%）， drug interactions and adverse reactions （218， E-mail：cputianxin@163.com 60.06%）. Only 69 institutions （19.01%） had a separate electronic information recording system， while 48 institutions 58516003。E-mail：zhenjiancun@vip.163.com （13.22%） had established comprehensive quality management and evaluation improvement systems. In terms of value embodiment， 141 institutions （38.84%） did not provide any form of compensation to relevant pharmacists. “Closely linked to enhancing patient satisfaction and improving services” was the most significant experience influencing medication reconciliation work（192， 52.89%）， while “the shortage of talent which meet the relevant requirements” stands as the primary challenge faced by medical institutions at all levels（238， 65.56%）. CONCLUSIONS The release of the standards has effectively improved the development rate of medication reconciliation in national medical institutions. However， there is still room for improvement in various aspects， including the allocation of personnel for medication reconciliation services， service content， information management， and the construction of quality control and evaluation systems.

OBJECTIVE To investigate the development and current status of medication education in domestic medical institutions， aiming to provide reference and suggestions for better development of medication education. METHODS The online questionnaire survey was conducted in March 2023 to investigate the implementation of medication education in medical institutions at all levels nationwide； descriptive analysis and influencing factors analysis were conducted. RESULTS A total of 1 368 questionnaires were recycled， 1 304 of which were effective questionnaires， with the effective rate of 95.32%. The average rate of providing medication education was 73.62% in medical institutions nationwide， 76.05%， 67.68% and 73.76% respectively in Eastern， Central and Western regions， 87.11%， 60.57% and 46.32% respectively in tertiary， secondary and primary medical institutions. The commonest place and way of carrying out medication education were dispensing window and oral instructions， and both were more diverse in tertiary medical institutions， compared with second and primary medical institutions. The median annual service volume of medication education in medical institutions PUMCH-A- at all levels was 500 people； the higher the level of medical institutions， the larger the annual service volume of medication education （P＝0.023）. More than half of medical institutions didn’t have any form of compensation for medication education， which was mostly reflected in the workload of medical institutions with compensation. Grade of medical institutions， degree of information and automation were the major influencing factors of carrying out medication education. CONCLUSIONS The ratio of carrying out medication education is improved in the central region in China in recent years， compared with 2019； while that of primary institutions in all regions is at a low level and should be improved. The place of carrying out medication education should be set according to the characteristics of medical institutions， and medication education forms should be enriched as much as possible. The quantity and quality of medication education talents still need to be improved. Compensation for pharmaceutical care should be continually explored and implemented to prompt high-quality and sustainable development of medication education.