Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (I_Na.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC₅₀) values of Mel on transient sodium current (I_Na.T) and specific I_Na.L opener 2 nmol·L^-1 sea anemone toxins II (ATX II) increased I_Na.L were 686.615 and 7.37 μmol·L^-1, respectively. Mel did not affect L-type calcium current (I_Ca.L), transient outward current (I_to), and AP. In addition, 16 μmol·L^-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking I_Na.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).

This study using maltodextrin as raw material, 1%-5% polyvinylpyrrolidone K30 as template agent, 1%-5% ammonium bicarbonate as pore-forming agent, curcumin and ibuprofen as model drugs. Porous maltodextrin was prepared by template and pore-forming agent methods, respectively. The structure and drug delivery behavior of porous maltodextrin prepared by different technologies were comprehensively characterized. The results showed that the porous maltodextrin prepared by pore-forming agent method had larger specific surface area (6.449 4 m²·g^-1) and pore size (32.804 2 nm), which was significantly better than that by template agent method (3.670 2 m²·g^-1, 15.278 5 nm). The adsorption kinetics between porous maltodextrin prepared by pore-forming agent method and curcumin were suitable for quasi-first order adsorption kinetic model, and that between porous maltodextrin and ibuprofen were suitable for quasi-second order adsorption kinetic model. While the adsorption kinetics between porous maltodextrin prepared by template agent method and two model drugs were both suitable for the quasi-first order adsorption kinetic model. In addition, the dissolution behavior analysis showed that the porous maltodextrin prepared by the two technologies can significantly improve the dissolution behavior of insoluble drugs, and the drug release was both carried out by diffusion mechanism, which suitable for the Peppas kinetic release model, but the porous maltodextrin prepared by template agent method had a faster release rate. The change of nozzle diameter had no significant effect on the adsorption process and drug release behavior of porous maltodextrin. In conclusion, the porous maltodextrins prepared by two different technologies were both beneficial to the delivery of insoluble drugs, and the template agent method was the best for delivery of insoluble drugs. This study can provide theoretical basis for the preparation of porous particles, promote the application of porous particles in insoluble drugs, and improve the bioavailability of insoluble drugs.

Objective To investigate the effect of fluid shear(FS)on apoptosis of glomerular epithelial cells(GECs)and the role of Piezo 1 protein in it.Methods GECs(glomerular epithelial cells)of SD rat were cul-tured.Fluid shear stimulation was simulated by a Flexcell-T5000 tensiometer.Apoptosis level was detected by flow cytometry.The expression of Piezo 1 proteins in GECs was detected by immunofluorescence staining.The activating of Piezo 1 channels by fluid shear was observed using Ca2+indicator(Cal-590 AM).The effect of Piezo 1 on apop-tosis in GECs was analyzed after modulating the function or expression of Piezo 1 protein using the chemical activa-tor Yoda1,the inhibitor GsMtx 4 was regulated by lentivirus Lv-shPiezo 1.Results Compared with the blank controlgroup,apoptosis increased in the fluid shear group(P＜0.05).The rate of apoptosis increased with the enhancing of fluid shear strength;Piezo 1 was commonly expressed in GECs.Fluid shear activated Piezo 1 chan-nel and enhanced expression of Piezo 1.The agonist Yoda1 promoted the apoptosis of GECs GsMtx 4 inhibited the apoptosis induced by fluid shear.Lv-shPiezo 1 knocked down the expression of Piezo 1 in GECs and the apoptosis rate of GECs in the knockdown group was reduced as compared to that in the control group and Lv-Ctrl group(P＜0.05).Conclusions Fluid shear may promote apoptosis of GECs by activation of Piezo 1 and by enhancing expression of Piezo 1.

This research established a high-performance liquid chromatography(HPLC) method for simultaneous determination of isoorientin, orientin, vitexin, and isovitexin in Commelina communis to conduct content difference analysis and quality evaluation of 62 batches of C. communis from different origins. The HPLC content determination was performed on a Dikma Platisil ODS chromatographic column(4.6 mm×250 mm, 5 μm), with acetonitrile-0.1% formic acid(14∶86) as the mobile phase. The detection wavelength was set at 348 nm, the flow rate was 1.0 mL·min~(-1), and the column temperature was 35 ℃. The differences in origins and quality of 62 batches of C. communis were studied by chemometrics. The results showed that the determination of four components mani-fested a good linear relationship in the range of mass concentration(r>0.999 9), and the average recovery rate was 96.17%-103.0%. The relative standard deviations(RSDs) of precision, stability, and repeatability were all less than 2.0%. The content of four components from high to low was isoorientin>isovitexin>orientin>vitexin. Forty-seven batches of C. communis with clear origins were classified into six categories by chemometrics. C. communis from different origins had different qualities. Generally, C. communis from Western China, Central China, and South of China had superior qualities. The HPLC method established in this study is specific, simple, and efficient, which provides references for the comprehensive evaluation of the quality of C. communis. The chemometrics shows that the qualities of C. communis from different origins are largely different. Isoorientin can be used as an index to determine the content of C. communis, and its content limit should be set no less than 0.023%.
Commelina ; Chemometrics ; Drugs, Chinese Herbal/chemistry* ; China ; Chromatography, High Pressure Liquid/methods*

Paris rugosa(Melanthiaceae) only grows in Yunnan province of China at present, and its chemical constituents have not been systematically studied. In this study, nine compounds, including one new compound pariposide G(1) and eight known compounds of cerin(2), stigmast-4-en-3-one(3), β-ecdysone(4), ophiopogonin C'(5), methyl protogracillin(6), gracillin(7), parissaponin H(8), and parisyunnanoside G(9), were isolated and identified from the ethanol extract of P. rugosa rhizomes by column chromatography methods and semi-preparative high-performance liquid chromatography(HPLC). Compounds 1-9 were isolated from this plant for the first time. The antibacterial and antifungal activities of all the compounds were evaluated. The results showed that ophiopogonin C' had strong inhibitory effects on Candida albicans [MIC_(90)=(4.68±0.01) μmol·L~(-1)] and the fluconazole-resistant strain of C. albicans [MIC_(90)=(4.66±0.02) μmol·L~(-1)].
Anti-Bacterial Agents ; Candida albicans ; China ; Liliaceae ; Melanthiaceae ; Rhizome

Objective:To compare the self-evaluated learning behavior and achievement of eight-year-program clinical medical students on online and offline problem-based learning (PBL), and to provide references and suggestions for successful implementation of online PBL teaching.Methods:During the three semesters of September 2020 to January 2022, a survey was performed on 100 clinical medical students of 2018 eight-year program on online or offline PBL teaching in Xiangya School of Medicine, Central South University. At the end of PBL courses, the students received questionnaires to self-assess their learning behavior and achievement in online or offline PBL teaching. The data were analyzed using the paired rank sum test with the use of SPSS 26.0.Results:Before class, there were no significant differences in learning behaviors including preparation time, communication with classmates, and materials collecting and sorting between students on online and offline PBL teaching ( P>0.05). In class, no significant differences were found in students' initiative of speaking and degree of satisfaction with classmates' speaking between online and offline teaching ( P>0.05), but the students on offline teaching showed significantly better concentration of attention ( Z=-4.24, P<0.001), listening to classmates' speeches ( Z=-3.42, P=0.001), and classmates' interaction ( Z=-3.11, P=0.002) compared with those on online teaching. No significant differences were observed between online and offline PBL teaching in students' self-evaluated learning achievements including improvements in autonomous learning ability, problem-solving ability, and literature inquiry skills ( P>0.05). Conclusion:Students on online PBL teaching have generally as good pre-class preparation and in-class learning performance as those on offline PBL teaching, indicating that the online PBL mode can be well implemented, and it can also ensure almost the same learning achievement as offline teaching.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*