ObjectiveTo elucidate the chemical composition of Danshenyin and its blood components in rats after oral administration. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） coupled with PeakView 1.2 software was used to systematically characterize and identify the components of Danshenyin aqueous extract and its migratory components in rat blood after oral administration based on the retention time， quasi-molecular ion peaks， secondary fragmentation ions， and literature reports， and a preliminary compounds identification of Salviae Miltiorrhizae Radix et Rhizoma aqueous extract， the co-decoction of Santali Albi Lignum and Amomi Fructus was carried out to attribute the chemical constituents of the aqueous extract of Danshenyin. ResultsA total of 73 compounds， including 21 phenolic acids， 23 diterpenes， 6 flavonoids， 7 organic acids， 3 volatile oils and 13 others， were identified from the aqueous extract of Danshenyin. And 36 prototypes and 15 metabolites were identified in rat plasma， the major metabolic pathways included reduction， hydration， hydroxylation， demethylation， methylation， sulfation and others， these metabolites were mainly derived from tanshinones and salvianolic acids. ConclusionThe main blood components of the aqueous extract of Danshenyin are salvianolic acids and tanshinones， which may be the material basis of the efficacy. This study can provide reference for pharmacological research， quality control， and clinical application of Danshenyin.

Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

AIM: To predict the core targets and related signaling pathways of Yi-xin-yin oral liquid for the treatment of arrhythmia, heart failure and myocarditis based on UHPLC-Q-TOF/MS, network pharmacology, molecular docking methods, cell experiments, according to the“homotherapy for heteropathy”theory in traditional Chinese medicine. METHODS: UHPLC-Q-TOF / MS was used to analyze and identify the chemical composition of Yi-xin-yin oral liquid Extract and the blood-absorbing components of rats oral administrated with Yi-xin-yin oral liquid extract, which compounds were applied in the databases searching for the potential targets (TCMSP, SwissTargetPrediction) and disease targets (OMIM, Genecard). Venn diagram was used for target intersection, and the subsequent protein-protein interaction network obtained core targets by STRING11.5 database, and then construct a "disease-component-target" network by cytoscape3.9.0. Finally, DAVID database was used to analysis GO function and KEGG enrichment analysis of core targets, and molecular docking validation was performed using Autodock vina software. And, validated with H9c2 cells for potential active ingredients and targets. RESULTS: A total of 156 compounds were identified from Yi - xin-yin Oral Liquid extract; 34 compounds were identified from rat serum, including 6-gin-gerol, isoliquiritigenin, glycyrrhizic acid and other compounds, and 139 intersecting targets were obtained. The KEGG pathway enrichment analysis mainly involved the TNF signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway and so on. The TNF and IL-6 targets were selected for molecular docking with the main compounds, and the docking results were good (less than -5 kcal/mol). In vitro cellular experiments have shown that Yi-xin-yin oral liquid can exert therapeutic effects by regulating TNF and IL-6. CONCLUSION: The main potential active ingredients of Yi-xin-yin oral liquid may be isoliquiritigenin, glycyrrhetinic acid, calycosin-7-glucoside, salvianolic acid B, and 6-gingerol, which mainly act on TNF, IL-6 and other targets to regulate specific signaling pathways and exert therapeutic effects.

ObjectiveTo understand the epidemiological characteristics of syphilis in Ruian City, so as to provide a scientific basis for developing syphilis prevention and control strategies. MethodsDescriptive epidemiological methods were used to investigate the infection status of syphilis cases reported among the permanent resident population in Ruian City from 2014 to 2023, and its epidemiological characteristics were analyzed. ResultsA total of 5 482 syphilis cases were reported in Ruian from 2014 to 2023, with a male-female ratio of 1∶1.47. The average annual incidence rate from 2014 to 2023 was 37.51/100 000, with a declining trend in the incidence rate among females (APC=-4.78%, P<0.05). The incidence of primary and secondary syphilis decreased, while the proportion of latent syphilis cases increased. No cases of congenital syphilis were reported from 2017 to 2023. The majority of cases (60.29%) were reported among individuals aged 20‒<50 years. In terms of occupation, the highest proportion was found among housekeepers and the unemployed, constituting 42.70% the total cases. Dermatology departments reported the most cases in medical institutions, accounting for 33.38% of the total cases. The most likely route of infection was heterosexual transmission, accounting for 85.84%. ConclusionThe incidence of syphilis among females in Ruian City shows a declining trend, but the overall situation remains concerning. Prevention and control efforts should be intensified among key groups and high-risk populations, along with an enhancement on health education to curb the spread of syphilis.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

Objective:To investigate the efficacy and safety of nasal continuous positive airway pressure (NCPAP) combined with inhalation of pulmonary surfactant (PS) using vibrating mesh nebulizers in the treatment of neonatal respiratory distress syndrome (RDS).Methods:A prospective study was performed on premature infants with RDS admitted to the First Affiliated Hospital of Bengbu Medical College between December 2020 and June 2021. They were randomly assigned into vibrating mesh atomization technology group and intubation-surfactant-extubation (INSURE) technology group. The two groups were treated with NCPAP combined with PS. PS in the vibrating mesh atomization technology group was inhaled into the lungs by the new vibrating mesh atomization technology, while PS in the INSURE group was injected into the lungs by endotracheal tube. The pH value, arterial partial pressure of carbon dioxide (PaCO 2), oxygenation index (PaO 2/FiO 2), mechanical ventilation via endotracheal tube (MVET) demand rate, duration of respiratory support, secondary use of PS, complications, and hospital mortality were compared between the two groups. The occurrences of adverse events in the two groups were recorded. Results:A total of 42 preterm infants were finally enrolled, including 20 cases in the vibrating mesh atomization technology group and 22 cases in the INSURE technology group. There were no significant differences in blood gas analysis and PaO 2/FiO 2 before PS administration between the two groups. One hour after PS administration, blood gas analysis and PaO 2/FiO 2 were significantly improved in both groups. Compared with the INSURE technology group, the improvement of PaO 2/FiO 2 was more obvious in the vibrating mesh atomization technology group [mmHg (1 mmHg≈0.133 kPa): 198±34 vs. 173±39, P < 0.05], but no significant difference in pH value or PaCO 2 was found between the two groups. The duration of respiratory support in the vibrating mesh atomization technology group was significantly shorter than that in the INSURE technology group (hours: 96±13 vs. 120±18, P < 0.01), but there was no statistical difference in MVET demand rate [5.0% (1/20) vs. 13.6% (3/22), P > 0.05]. The incidence of periventricular-intraventricular hemorrhage (PVH-IVH) in the vibrating mesh atomization technology group was less than that in the INSURE technology group [0% (0/20) vs. 18.2% (4/22)], but no statistical difference was found ( P > 0.05). No significant differences in the secondary use rate of PS and incidence of bronchopulmonary dysplasia (BPD) or other complications were found between the vibrating mesh atomization technology group and the INSURE technology group [5.0% (1/20) vs. 9.1% (2/22), 5.0% (1/20) vs. 4.5% (1/22), both P > 0.05]. There were no deaths or serious adverse events such as pneumothorax, pulmonary hemorrhage, periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC) in both groups. Conclusion:Compared with the INSURE technique, NCPAP combined with vibrating mesh atomization technology was also effective and safe in the treatment of RDS, which could significantly improve PaO 2/FiO 2 and shorten the duration of respiratory support. Thus, it was worthy of clinical popularization and application.

Objective:To investigate the effect of antidepressant therapy on cellular immunity and quality of life of patients with depression after thoracoscopic radical resection of esophageal cancer.Methods:Between June 2015 to March 2019, our hospital during the period of line thoracoscope comorbid depressive patients, 186 cases of esophageal cancer radical, according to the indicator method were randomly divided into treatment group and the control group (n=93), the treatment group after surgery for antidepressant treatment, the control group did not give any postoperatively in patients with depressive drugs treatment, routine for psychological counseling. Self-rating Depression Scale SDS and Generic Quality of Life Inventory-74 (GQoli-74) were used to evaluate the changes of depression status and Quality of Life in 2 groups before and after treatment. Flow cytometry was used to detect the levels of CD 4+ and CD 8+ subsets in peripheral blood to evaluate the changes of immune system function in 2 groups before and after treatment. Results:After treatment, the SDS score of the treatment group was significantly lower than that before treatment, the difference was statistically significant( P<0.05), while the SDS score of the control group was not significantly changed before and after treatment, the difference was not statistically significant( P>0.05). After antidepressant treatment, CD 4+ and CD 4+ /CD 8+ levels in the immune system in the treatment group were significantly increased, and CD 8+ levels were significantly decreased, with statistical significance ( P<0.05), while CD 4+ , CD 8+ and CD 4+ /CD 8+ levels in the control group were not significantly changed before and after treatment. There was no significant difference ( P>0.05). After treatment, the body function, psychological function, social function, material state and total score of quality of life of patients in the treatment group were significantly improved compared with before treatment, the difference was statistically significant ( P<0.05), while the score of quality of life of patients in the control group was not significantly changed before and after treatment, the difference was not statistically significant ( P>0.05). Conclusion:Antidepressant therapy can significantly improve the depression status of postoperative esophageal cancer patients, and improve the immune system function and quality of life.

Objective To optimize the manufacture process for Zhibai Anshen oral liquid. Methods The orthogonal designed experiments were conducted to monitor the effects of three factors on the content of mangiferin. The three factors included the amount of water, extraction time and alcohol precipitation concentration. Six month accelerated stability study and twelve month long term stability study were performed. Results Optimum percolation process was boiling the mixture with 10 times of water for 1 hour, followed by deposition with 60% alcohol. Conclusion This optimized process can be used for mass production.

[Abstract] Objective:ToinvestigatetheroleofmiR-125a-5pininducingthegefitinib(Gef)-resistance of non-small cell lung carcinoma (NSCLC) cells and its possible mechanism. Methods: Human NSCLC drug-resistant cell line A549/GR and NSCLC cell line A549 were chosen for this study. miR-125a-5p mimic, miR-125a-5p inhibitor, pcDNA3.1-APAF1 and empty vector pcDNA3.1 were transfected into A549/GR cells. The expression level of miR-125a-5p in cell lines was detected by qPCR. MTT, Transwell and Flow cytometry were used to detect the effects of Gef on proliferation, migration and apoptosis of cell lines, respectively. The targeting relationship between miR-125a-5p and APAF1 (apoptotic peptidase activating factor 1) was verified by Dual-luciferase reporter gene system. In addition, the expression of APAF1 protein in A549/GR cells was detected by Western blotting. The expression levels of caspase-3 and caspase-9 were assessed by colorimetry. Results: Expression level of miR-125a-5p was upregulated significantly in Gefresistant A549/GR cells (P<0.01). AndtheinfluencesofGefonA549/GRcellswereenhancedby knockdown of miR-125a-5p, including inhibiting cell proliferation and migration (all P<0.05) and inducing apoptosis (P<0.01). Dual luciferase reporter gene assay confirmed that miR-125a-5p targeted APAF1 and negatively regulated its expression. Furthermore, by targetedly downregulating APAF1, miR-125a-5p alleviated the inhibition of proliferation and migration (all P<0.05) and promotion of apoptosis (P<0.05) of A549/GR cells caused by Gef, and attenuated Gef-induced upregulation of apoptosis-related proteins caspase-3 and caspase-9 (all P<0.05). Conclusion: miR-125a-5p promotes Gef-resistance of A549/GR cells, and the underlying mechanisms are promotion of proliferation, migration and inhibition of apoptosis of non-small cell lung cancer cells by targetingAPAF1.

Objective:To investigate the effects of sodium arsenite (NaAsO 2) on the expression of sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator activated receptor α (PPARα) and fatty acid synthase (FAS) in human liver cells (L-02 cells). Methods:L-02 cells were cultured in vitro, and exposed to NaAsO 2 at 0 (control), 2, 4, 8, 16, 32, 64 and 128 μmol/L for 24 h, respectively, and the cell survival rate was determined by CCK-8 method. And a fitting curve was made to calculate the half inhibitory concentration (IC 50), subsequent experiments were carried out with 0, 1/8, 1/4 and 1/2 of IC 50 as arsenic exposure doses. Glycerol phosphate oxidase-catalase (GPO-PAP) method was used to detect the content of triglyceride (TG) in cells; the mRNA expression levels of SREBP-1c, PPARα and FAS were detected by Real-time PCR; and the protein expression levels of SREBP-1c and PPARα were detected by Western blotting. Results:The cell survival rates of 8, 16, 32, 64 and 128 μmol/L NaAsO 2 groups [(92.000 ± 1.414)%, (91.000 ± 0.000)%, (76.500 ± 0.707)%, (53.000 ± 1.412)%, (47.000 ± 1.412)%] were significantly lower than that of the control group [(100.000 ± 0.000)%, P < 0.01]. The IC 50 was 64 μmol/L, and subsequent experiments were conducted with 0 (control), 8, 16 and 32 μmol/L NaAsO 2, respectively. Compared with the control group [(1.000 ± 0.000) mmol/g prot], TG contents of 8, 16 and 32 μmol/L NaAsO 2 groups [(0.691 ± 0.064), (0.474 ± 0.162), (0.184 ± 0.045) mmol/g prot] were significant decreased ( P < 0.01). Compared with the control group, the mRNA expression levels of SREBP-1c, PPARα, FAS, and the protein expression levels of SREBP-1c and PPARα in NaAsO 2 groups were significantly decreased ( P < 0.01 or < 0.05). Correlation analysis showed that NaAsO 2 content was negatively correlated with TG content, SREBP-1c and PPARα protein expression levels ( r =-0.954,- 0.875,-0.965, P < 0.01). Conclusion:NaAsO 2 can reduce the TG content and the expression of lipid metabolism related genes SREBP-1c, PPARα and FAS in L-02 cells, suggesting that arsenic-induced liver injury can cause lipid metabolism disorders.