Nine compounds were isolated and purified from 90% ethanol extract of Alstonia mairei Lévl by using various chromatographic methods, including silica gel, SephadexLH-20, MCI Gel and ODS column chromatography, combined with semi-preparative liquid phase separation methods. Modern spectroscopic methods (1D and 2D NMR, UV, IR, MS, etc.) were used to identify the structures of the isolated compounds. They were identified as mairoside A (1), 3′,6-di-O-sinaloylsucrose (2), myristic acid (3), methyl myristate (4), ethyl myristate (5), 3,4,5-trimethoxycinnamic acid (6), 3,4,5-trimethoxybenzoic acid (7), vinoline (8), kaempferol-3-O-rutinoside (9), among which compound 1 is a new glycoside, compounds 4 and 5 are new natural products, and the nuclear magnetic data of compound 4 were reported for the first time.

As a new type of production factor that can empower the development of new quality productivity, the data element is an important engine to promote the high quality development of the industry. Traditional Chinese medicine(TCM) dispensing is the most basic work of TCM clinical pharmacy, and its quality directly affects the clinical efficacy of TCM. The integration of data elements and TCM dispensing can stimulate the innovation and vitality of the TCM dispensing industry and promote the high-quality and sustainable development of the industry. A large-scale, detailed, and systematic study on TCM dispensing was conducted. The innovative practice path of data fusion construction in the whole process of TCM dispensing was investigated by integrating the digital resources "nine full activities" of TCM dispensing, creating the digital dictionary of "TCM clinical information data elements", and exploring innovative applications of TCM dispensing driven by data and technology, so as to promote the standardized, digital, and intelligent development of TCM dispensing in medical health services. The research content of this project was successfully selected as the second batch of "Data element×" typical cases of National Data Administration in 2024, which is the only selected case in the field of TCM.
Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal ; Humans

Objective To investigate whether Liuwei Dihuang Pills enhances the antigen cross-presenting ability of dendritic cell(DC)by increasing gap junctional intercellular communication(GJIC),and to explore the mechanisms involved.Methods Western Blot and immunofluorescence were used to observe the effects of Liuwei Dihuang Pills-containing serum on the expression and membrane localisation of gap junction protein connexin43(Cx43)in mouse melanoma cells(B16);Calcein-AM/DiI fluorescence tracer assay was used to observe the effects of Liuwei Dihuang Pills-containing serum on the function of GJIC in B16 cells;flow cytometry was used to observe the role of GJIC in the enhancement of DC antigen presenting ability by Liuwei Dihuang Pills-containing serum;and propidium iodide(PI)/Hoechst staining assay was used to observe the immunocidal effect of CD8+ T-lymphocytes.Results Western Blot and immunofluorescence experiments showed that Liuwei Dihuang Pills-containing serum led to the up-regulation of Cx43 expression;fluorescence tracer experiments proved that the GJIC function of B16 cells was significantly enhanced by Liuwei Dihuang Pills-containing serum;flow cytometry analyses showed that the DC antigen-presenting ability was enhanced by Liuwei Dihuang Pills-containing serum;and the results of PI/Hoechst staining showed that the immuno-killing effect of CD8+T-cells was more significant after the intervention of Liuwei Dihuang Pills-containing serum in B16-OVA.Conclusion Liuwei Dihuang Pills improve the GJIC function by up-regulating the Cx43 expression of melanoma cells,and then enhance the cross-presenting ability of DCs thus activating stronger CD8+ T-cell immunocidal responses.

Objective:To investigate the relationship between heart rate variability(HRV), deceleration capacity(DC) and cardiovascular metabolic disease(CMD) in children and adolescents with normal weight obesity(NWO).Methods:A total of 200 children and adolescents aged 6-17 who underwent normal physical examination in Chengdu Women′s and Children′s Central Hospital from December 2022 to June 2023 were included in this retrospective case-control study.They were divided into the NWO group, normal weight lean(NWL) group, and overweight-obesity(OW-OB) group according to their body mass index(BMI) and body fat percentage(BF%).Fifty children were enrolled into the NWO group; fifty-one children were enrolled into the NWL group; and 99 children were enrolled into the OW-OB group.All the subjects received 24-hour heart monitoring, and their HRV indexes, such as the standard deviation of N-N interval in normal sinus(SDNN), the standard deviation of the mean value N-N intervals every 5-minute(SDANN), the mean of the standard deviations of all N-N intervals for each 5-minute segment of 24 hours(SDNNindex), the root mean square of successive N-N interval difference(rMSSD), the proportion of N-N 50(the successive N-N interval differences>50 ms) in the total number of N-N intervals(pNN50), and DC were automatically calculated.Blood pressure, fasting blood glucose and blood lipids were measured, and the cardiometabolic risk score(CRS) was obtained through the accumulation of relevant factors.The general data, SDNN, SDANN, SDNNindex, rMSSD, pNN50, DC and CRS of the three groups were compared by variance analysis.Spearman correlation and multivariate Logistic regression were used to analyze the risk factors affecting CRS.Results:There was no significant difference in age, gender and other general information among the three groups(all P>0.05).SDNN in the NWO, NWL, and OW-OB groups were(120.88±16.36) ms, (129.07±16.36) ms, and(109.29±16.38) ms, respectively( F=26.231, P<0.001); SDANN were(64.44±11.61) ms, (66.25±8.34) ms, and(61.70±6.85) ms, respectively( F=5.048, P=0.007); rMSSD were(27.02±3.87) ms, (27.51±5.92) ms, and(25.12±6.78) ms, respectively( F=3.328, P=0.038); pNN50 were(12.62±4.04)%, (13.39±2.26)%, and(11.22±2.93)%, respectively( F=9.099, P<0.001); DC were(4.83±0.20) ms, (4.94±0.33) ms, and(4.63±0.28) ms, respectively( F=23.496, P<0.001)and CRS was 0.94±0.87, 0.69±0.19 and 1.57±1.07, respectively( P<0.01).The differences between the three groups were statistically significant.Spearman correlation analysis showed that BMI( r=0.211, P=0.003) and BF%( r=0.558, P<0.001) were significantly positively correlated with CRS, while SDNN( r=-0.258, P<0.001) and DC( r=-0.499, P<0.001) were significantly negatively correlated with CRS.Multivariate Logistic regression analysis showed that BF%(95% CI: 0.098-0.265, P<0.001) and DC(95% CI: -3.962--1.391, P<0.001) were independent risk factors for predicting CMD. Conclusions:Increased BF% and decreased DC are independent risk factors for CMD.Analysis of body composition and HRV in children and adolescents can help to identify potentially high-risk groups more accurately, intervene early, and reduce the risk of CMD.

Atherosclerosis caused by disorders of lipid metabolism is the main pathological basis of atherosclerotic cardiovascular disease.Statins are the cornerstone of lipid-modulating therapy for this type of disease,but in practice there are still some patients with suboptimal lipid management.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors have been gradually applied as a new class of lipid-modulating drugs for the treatment in patients with this type of disease,and recent studies have shown that in addition to regulating lipid metabolism,PCSK9 inhibitors also have potential anti-inflammatory and anti-platelet activation effects.This article sorts out the multiple pharmacological mechanisms of action of PCSK9 inhibitors and the current status of clinical research of PCSK9 inhibitors.Besides,it discusses the factors that may affect the efficacy of PCSK9 inhibitors,in order to provide a reference for the safe and rational medication of PCSK9 inhibitors.

Objective:To investigate the effects of PD-1 monoclonal antibody therapy on the peripheral and local immune microenvironment of patients with microsatellite instability-high(MSI-H)rectal cancer.Methods:Samples of peripheral blood and tumor biopsy were collected from a patient with MSI-H rectal cancer before and after PD-1 monoclonal antibody treatment.The samples were dissociated into single-cell suspensions using a combination of enzymatic and mechanical methods.Immune-related marker expression on peripheral and tumor-infiltrating im-mune cells was analyzed using single-cell mass cytometry(CyTOF).Results:According to the results of CyTOF analysis,CD45+immune cells in the peripheral blood and tumor tissues were categorized into 39 and 34 cell subsets,respectively,before and after PD-1 monoclonal antibody treatment(the correlation is unclear and ambiguous).After PD-1 monoclonal antibody treatment,differences were observed in the relative abundance of immune cell subsets:B cells significantly decreased in the peripheral blood,while B cells and γδT cells significantly increased in the tumor tissue;neutrophils significantly decreased,and the proportion of CD4+TEM cells in T cell subsets significantly increased,whereas CD4+Treg cells significantly decreased.Additionally,there were differences in the expression of immune-related markers in multiple immune cell subsets in both peripheral blood and tumor tissues,with CCR6 showing a significant increase in expression across all subsets,while ICOS and PD-1 expressions in T cell subsets were significantly reduced(the specific tissues for these cells or factors are unclear).Conclusion:After PD-1 monoclonal antibody treatment in MSI-H rectal cancer,changes occurred in the composition of immune cells and the expression of immune-related markers in both peripheral blood and tumor tissues.This study reveals the dynamic adjustment of the immune microenvironment and provides important evidence for understanding the therapeutic mechanism of PD-1 monoclonal antibodies.

Objective: To understand the performance of 2019-nCoV nucleic acid detection in screening of contacts of COVID-19 cases in same flights and provide evidence for the effective screening of persons at high risk for the infection in domestic flights. Methods: The information of passengers who took same domestic flights with COVID-19 cases in China from April 1, 2020 to April 30, 2022 were retrospectively collected,and χ² test was used to analyze positive nucleic acid detection rates in the passengers in different times before the onsets of the index cases, in different seat rows and in epidemic periods of different 2019-nCoV variants. Results: During the study period, a total of 433 index cases were identified among 23 548 passengers in 370 flights. Subsequently, 72 positive cases of 2019-nCoV nucleic acid were detected in the passengers, in whom 57 were accompanying persons of the index cases. Further analysis of the another 15 passengers who tested positive for the nucleic acid showed that 86.67% of them had onsets or positive detections within 3 days after the diagnosis of the index cases, and the boarding times were all within 4 days before the onsets of the index cases. The positive detection rate in the passengers who seated in first three rows before and after the index cases was 0.15% (95%CI: 0.08%-0.27%), significantly higher than in the passengers in other rows (0.04%, 95%CI: 0.02%-0.10%, P=0.007),and there was no significant difference in the positive detection rate among the passengers in each of the 3 rows before and after the index cases (P=0.577). No significant differences were found in the positive detection rate in the passengers, except the accompanying persons, among the epidemics caused by different 2019-nCoV variants (P=0.565). During the Omicron epidemic period, all the positive detections in the passengers, except the accompanying persons, were within 3 days before the onset of the index cases. Conclusions: The screening test of 2019-nCoV nucleic acid can be conducted in the passengers took the same flights within 4 days before the onsets of the index cases on board. Passengers who seated within 3 rows from the index cases can considered as the close contacts at high risk for 2019-nCoV, for whom screening should be conducted first and special managements are needed. The passengers in other rows can be classified as general risk persons for screening and management.
Humans ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; China ; Nucleic Acids

Objective:A structural equation model of the influencing factors on caregiver preparedness at discharge of patients with chronic heart failure was constructed based on the individual and family self-management theory, and the main paths influencing caregiver preparedness were explored.Methods:This study was a cross-sectional survey. A total of 345 caregivers of patients with chronic heart failure who were hospitalized in the Fourth Affiliated Hospital of China Medical University from October 2020 to August 2021 were selected as research objects by convenience sampling method, and they were investigated by Caregiver Preparedness Scale, Family APGAR Index, Herth Hope Index, Social Support-Rating Scale, Simplified Coping Style Questionnaire. The influencing factors on caregiver preparedness at discharge of patients with chronic heart failure were analyzed.Results:The total score of Caregiver Preparedness Scale, Family APGAR Index, Herth Hope Index, Social Support-Rating Scale, and Positive and Negative Coping Subscale of Simplified Coping Style Questionnaire in patients with chronic heart failure was (20.79 ± 4.92), (8.05 ± 1.43), (35.34 ± 4.47), (43.89 ± 6.56), (24.38 ± 5.21), (11.21 ± 4.26) points. Caregiver preparedness in patients with chronic heart failure was positively correlated with family function, hope, positive coping and social support ( r values were 0.213-0.383, all P<0.01), and negatively correlated with negative coping ( r=-0.546, P<0.01). Family function and social support in patients with chronic heart failure could directly or indirectly affect caregiver preparedness (total effect value: 0.380, 0.212), hope and negative coping directly affected caregiver preparedness (total effect value: 0.200, -0.433), and could account for 39% of the total variation in caregiver preparedness. Conclusions:Caregiver preparedness of patients with chronic heart failure needs further improvement. The effective ways to improve caregiver preparedness are to pay attention to family function, improve hope level, increase social support and reduce negative coping.

Chronic heart failure is the end stage of heart diseases caused by multiple causes. Myocardial cell injury is the key cause of cardiac function deterioration. Ferroptosis, an iron-dependent programmed death mode, is characterized by iron overload and excessive accumulation of lipid peroxides. Studies have demonstrated that inhibiting ferroptosis has a protective effect on myocardial cells. The theory of "harmful hyperactivity and responding inhibition" is an important rule developed by physicians to explain the generation and restriction of the five elements and the pathological imbalance of the human body, and can guide medication. Correlating with the nature, humans need to rely on the law of responding inhibition to maintain the harmony of five Zang-organs and the steady state of Fu-organs. The pathogenesis of ferroptosis in chronic heart failure highly coincides with the process of failing to "inhibition and hyperactivity becoming harmful". The initial factor of ferroptosis is the deficiency of heart Qi, which results in the inability to maintain the balance of cardiomyocyte redox system. The involvement of the five Zang-organs leads to the loss of distribution of body fluid and blood. As a result, the phlegm turbidity, blood stasis, and water retention in the meridians occur, which are manifested as the accumulation of iron and lipid peroxides, which is the aggravating factor of ferroptosis. The two factors interact with each other, leading to the spiral development and thus aggravating heart failure. According to the traditional Chinese medicine(TCM) pathogenesis of ferroptosis, the authors try to treat the chronic heart failure by stages in accordance with the general principle of restraining excess and alleviating hyperactivity. The early-stage treatment should "nourish heart Qi, regulate the five Zang-organs, so as to restrain excess". The middle-stage treatment should "active blood, resolve phlegm, dispel pathogen, and eliminate turbidity", so as to alleviate hyperactivity. The late-stage treatment should "warm Yang, replenish Qi, active blood, and excrete water". Following the characteristics of pathogenesis, the TCM intervention can reduce iron accumulation and promote the clearance of lipid peroxide, thus inhibiting ferroptosis and improving cardiac function.
Humans ; Ferroptosis ; Lipid Peroxides ; Medicine, Chinese Traditional ; Heart Failure/drug therapy* ; Chronic Disease ; Iron ; Water

The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.
Polysorbates/chemistry* ; Flavonoids ; Pueraria ; Surface-Active Agents/chemistry* ; Ethanol ; Emulsions ; Particle Size ; Solubility