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.

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.

Objective:To evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and tislelizumab in the treatment of unresectable intrahepatic cholangiocarcinoma (ICC).Methods:The clinical data of 12 patients with unresectable ICC who received HAIC combined with lenvatinib and tislelizumab in the First Affliated Hospital of Soochow University from October 2021 to April 2023 were retrospectively analyzed. HAIC included gemcitabine plus oxaliplatin; this regimen was combined with lenvatinib and tislelizumab within 3-7 days after its initial administration. Relevant laboratory examinations were performed before each cycle of HAIC, and enhanced computed tomography/magnetic resonance imaging examinations were performed every 6-9 weeks. Tumor response to treatment was evaluated using the modified Response Evaluation Criteria in Solid Tumors. The objective response rate, disease control rate, progression-free survival, overall survival, and treatment-related adverse reactions of patients with ICC were statistically analyzed.Results:The objective response rate to HAIC combined with lenvatinib and tislelizumab was 6/12; the disease control rate was 8/12; the median progression-free survival was 11.8 months; and the median overall survival was 14.2 months. Three patients had grade Ⅳ adverse reactions (increased alanine aminotransferase and aspartate aminotransferase thrombocytopenia), while three patients had grade Ⅲ adverse reactions (increased total bilirubin, alanine aminotransferase, and aspartate aminotransferase). The remaining patients had grade Ⅰ-Ⅱ adverse reactions. There were no serious complications related to interventional surgery.Conclusions:Use of HAIC (gemcitabine plus oxaliplatin) combined with lenvatinib and tislelizumab in the treatment of unresectable ICC may be safe and feasible. Preliminary clinical studies have shown that this combination can improve the survival and prognosis of patients with ICC.

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 investi gate the role of clinical pharmacists in the treatment of delayed excretion of acute renal failure （ARF） with epileptic seizure caused by HD-MTX in a patient ，and to provide reference for rational drug use and pharmaceutical care in such type of patients. METHODS ：A patient with diffuse large B-cell lymphoma was given HD-MTX for chemotherapy，and ARF caused by delayed methotrexate excretion occurred on the second day after methotrexate administration. Clinical physicians adjusted the rescue dose and frequency of calcium folinate but the effect was poor. Clinical pharmacists analyzed the causes of delayed methotrexate excretion by reviewing literature and combining with the patient ’s condition. It was suggested to monitor the blood concentration of methotrexate ，strengthen alkalization and hydration ，increase the volume of intravenous sodium bicarbonate from 125 mL to 250 mL，take Sodium bicarbonate tablets orally ，and monitor the pH value of urine （pH value of urine maintained above 7）. In addition ，the pharmacist told the patient to drink water as much as possible to ensure the daily urine output reached 3 000 to 4 000 mL. The blood concentration of methotrexate was 16.14 μmol/L 44 h after administration ，which proved to be excretion delay. The patient had epileptic seizure on the 13th day after methotrexate medication. The physician gave sodium valproate 0.8 g intravenously to control epilepsy. The clinical pharmacist conducted pharmaceutical care for the patient ，and found that the compliance of the patient taking Sodium bicarbonate tablets and Sodium valproate tablets orally was not good ，so medication education and pharmaceutical care were conducted ，then the patient accepted and took the drugs on time. RESULTS ： The physician adopted the suggestions of the pharmacist to monitor the blood concentration of methotrexate and performed symptomatic treatment. The urine volume of the patient increased ，the edema was reduced ，serum creatinine gradually returned to normal，and renal function recovered gradually ；the symptoms of epilepsy was controlled. CONCLUSIONS ：In the treatment process of ARF complicated with epileptic seizure caused by excretion delay of HD-MTX ，the clinical pharmacist assisted physician to improve the treatment plan and conducted pharmaceutical care and medication education for the patient ，therefore ensure the safe and rational use of drugs .

AIM: The main chemical components of Yufang Fangji II (Hubei Fang) of COVID-19 were studied systematically and combined with network pharmacology to provide a reference for the study of its effective substances. METHODS: Ultra high-performance liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-Q-TOF/MS) was applied to identify the absorbed components of the prescription in rat plasma. TCMSP database and Swiss Target Prediction data platform were used to predict the target of the identified blood components, and network visualization software Cytoscape 3.7.2 was used draw the association network diagram, and GO enrichment analysis and KEGG pathway enrichment analysis were conducted for the key targets. With the help of CB-Dock online molecular docking platform, the molecular docking of key targets and blood entering compounds was carried out, and the docking combination with good affinity value was displayed by ligplot software to verify the preventive effect of Yufang Fangji II on COVID-19. RESULTS: A total of 52 chemical components identified in the prescription, in which 13 components were absorbed in the rat plasma as the prototype, and they were from Astragalus membranaceus, Atractylodes macrocephala, Saposhnikoviae Radix, Lonicerae Japonicae Flos, and Citri Reticulatae Pericarpium, respectively. These compounds were recognized to act on 17 core targets, including mapk3, TNF and other targets related to inflammation, MPO and other targets related to oxidative stress, VEGFR, KDR and other targets related to vascular endothelium. The results of molecular docking showed that the absorbed components had good binding activity with the key targets. CONCLUSION: Compounds in Yufang Fangji II are involved in regulating inflammation, oxidative stress, vascular and cellular physiological activities, which have preventive effects on COVID-19 through regulating IL-17, PI3K Akt, MAPK and other pathways.

ObjectiveTo investigate the value of ABCR clinical scoring system in guiding repeated transcatheter arterial chemoembolization (TACE) therapy for patients with hepatocellular carcinoma (HCC) and the treatment strategies for patients with an ABCR score of 1-3. MethodsThe patients with HCC who underwent TACE in The First Affiliated Hospital of Soochow University from January 2008 to December 2017 were enrolled. In order to investigate the effect of repeated TACE in patients with different ABCR scores, 229 patients who underwent repeated TACE consecutively (at least twice, without systemic therapy) were enrolled as group A, which was further divided into group A1 with 92 patients (an ABCR score of ≤0), group A2 with 78 patients (an ABCR score of 1-3), and group A3 with 59 patients (an ABCR score of ≥4). In order to investigate the survival time of patients with an ABCR score of 1-3 who received different regimens after first TACE therapy, 118 patients with an ABCR score of 1-3 who received TACE for the first time were enrolled as group B, which was further divided into group B1 with 78 patients (treated with TACE after first TACE therapy), group B2 with 21 patients (treated with TACE combined with sorafenib), and group B3 with 19 patients (treated with sorafenib alone). The survival of the above groups of patients were analyzed. The Fisher’s exact test was used for comparison of categorical data between groups, the Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison of survival time between groups. ResultsThe median survival time was 320 months (95% confidence interval ［CI］: 27.7-36.3) in group A1, 10.3 months (95%CI: 8.4-12.2) in group A2, and 4.6 months (95%CI: 3.7-5.5) in group A3. Group A1 had a better survival time than group A2 (χ2=106.99, P＜0.01), and group A2 had a better survival time than group A3 (χ2=49.66, P＜0.01). The median survival time was 10.3 months (95%CI: 8.4-12.2) in group B1, 14.8 months (95%CI: 7.8-21.8) in group B2, and 6.0 months (95%CI: 4.6-7.4) in group B3, and group B2 had a better survival time than group B1 (χ2=6.80, P＜0.01) and group B3 (χ2=29.89, P＜0.01). ConclusionThe ABCR score has a certain guiding significance for the treatment of HCC patients. Repeated TACE may be considered for patients with an ABCR score of ≤0, while patients with an ABCR score of ≥4 may not benefit from further TACE therapy, and TACE combined with sorafenib might bring maximum benefits to patients with an ABCR score of 1-3.