To analyze the approval for marketing, drug characteristics, and differences of novel hematological antineoplastic drugs between China and the United States, and provide reference for pharmaceutical management, drug research and development, drug review and approval in China.

The websites of the U.S. Food and Drug Administration (FDA) and the National Medical Products Administration of China and package insert of drug were searched, and the novel hematological antineoplastic drugs approved for marketing in the United States from 1997 to 2021 and China from 1999 to 2021 were collected. The drug names, approval types, approval dates, accelerated drug marketing registration procedures, drug action mechanism and indications were extracted, and the approval status and timeliness of new drugs, as well as the number of approvals for different types of drugs were analyzed.

From 1997 to 2021, a total of 69 novel hematological antineoplastic drugs approved in the United States, which included 42 new molecular entities and 27 new therapeutic biologics. Sixty-five drugs were approved through expedited development and review pathways. From 1999 to 2021, China approved a total of 36 novel hematological antineoplastic drugs, including 24, 11, and 1 for chemical drugs, biologics products, and traditional Chinese medicine, respectively. Twenty-five drugs were approved to use accelerated drug marketing registration procedures. The number of approved drugs in both countries has significantly increased from 2017 to 2021, with 26 (87%) out of 30 novel hematological antineoplastic drugs in the United States being the first global approval drugs, and 8 (32%) out of 25 novel hematological antineoplastic drugs in China being the first global approval drugs, and the average approval time for the other 17 drugs was 6 years later than that of the United States. The novel hematological antineoplastic drugs approved in China covered multiple drug targets, which were closer to the targets of new molecular entities approved in the United States and could be used to treat multiple types of hematology neoplasms. However, the biological targets were still limited compared with the United States, which mainly used for lymphoid tissue tumors. There were no drugs used for myeloid tumors, and the types were relatively single. From 2017 to 2021, among the 17 novel hematological antineoplastic drugs approved for marketing in China had been approved in the United States, only 6 drugs had the same indications as the United States, and one drug had more indications than the United States.

In recent years, the number of novel hematological antineoplastic drugs approved for marketing in China has significantly increased. Diverse accelerated drug marketing registration procedures has been used for the review and approval of novel hematological antineoplastic drugs. The target types of approved novel hematological antineoplastic drugs have increased, but the timeliness of new drug review and approval and the international influence of domestic drugs still need to be enhanced. The research and development of domestic novel hematological antineoplastic drugs should avoid single target aggregation, and pay attention to the exploration of new indications of drugs and new combined treatment schemes.

To investigate the effective dose of esketamine inhibiting responses to gastroscopy insertion when combined with propofol in patients of different ages.

Patients scheduled for painless gastroscopy were selected and divided into three groups according to different ages: youth group (aged 1 - 40 years), middle age group (aged 41 - 64 years), and elderly group (aged 65 - 80 years). All patients were given propofol 1.5 mg·kg^-1 combined with esketamine under intravenous anesthesia, dose of esketamine was determined by up-and-down sequential method, the initial dose of esketamine set at 0.2 mg·kg^-1, and the common ratio of esketamine dose in adjacent patients was 1.1. When the response to gastroscopy insertion was positive reaction, the dose of esketamine was increased in the next patient, and decreased vice versa. The test ended after 7 crossovers were obtained. Probit analysis was used to calculate the median effective dose (ED₅₀), 95% effective dose (ED₉₅), and the corresponding 95% confidence interval (CI). Vital signs, awakening time, and the occurrence of adverse reactions were recorded.

The effective dose of esketamine inhibiting responses to gastroscopy insertion in patients of different ages when combined with propofol 1.5 mg·kg^-1: the ED₅₀ of the young group was 0.192 mg·kg^-1 (95% CI: 0.181 to 0.202 mg·kg^-1), ED₉₅ was 0.209 mg·kg^-1 (95% CI: 0.200 to 0.255 mg·kg^-1) ; the ED₅₀ of the middle age group was 0.157 mg·kg^-1 (95% CI: 0.106 to 0.183 mg·kg^-1), ED₉₅ was 0.202 mg·kg^-1 (95% CI: 0.179 to 0.576 mg·kg^-1) ; the ED₅₀ was 0.113 mg·kg^-1 (95% CI: 0.085 to 0.131 mg·kg^-1) and ED₉₅ was 0.150 mg·kg^-1 (95% CI: 0.131 to 0.303 mg·kg^-1) in the elderly group. There were 2 cases of hypotension and 1 case of respiratory depression in the elderly group, while there were no significant adverse reactions in the other two groups.

When combined with propofol 1.5 mg·kg^-1, the ED₅₀ and ED₉₅ of esketamine inhibiting response to gastroscopy insertion in patients of different ages show decreasing trends with age.

To investigate the efficacy and safety of edaravone and dexborneol in the treatment of acute cerebral infarction.

A total of 120 patients with acute cerebral infarction for intravenous thrombolysis were selected, and were treated with alteplase 0.9 mg·kg^-1 for thrombolysis. Then they were divided into control group and study group (n=60 in each group). The study group received intravenous infusion of 37.5 mg of edaravone and dexborneol injection after thrombolysis, once every 12 hours, for a course of ≤14 days. The baseline data, National Institutes of Health Stroke Scale (NIHSS) scores before and after thrombolysis at 30 minutes, 24 hours and 7 days, modified Rankin Scale (mRS) scores before and after thrombolysis at 24 hours and 7 days, the levels of hypersensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6) before and after thrombolysis at 7 days, and the occurrence of adverse events were observed.

After 30 minutes of thrombolysis, the NIHSS scores of the two groups were significantly reduced compared with before thrombolysis (P<0.05), and there was no significant difference between the groups (P>0.05). At 24 hours and 7 days after thrombolysis, the NIHSS and mRS scores of the two groups were significantly lower than before thrombolysis, and the study group was lower than the control group (P<0.05). The total effective rates of the study group and the control group were 80% and 63%, respectively, with significant differences between the two groups (P<0.05). At 7 days after thrombolysis, the levels of hsCRP and IL-6 in the two groups were significantly lower than those before thrombolysis (P<0.05), while the study group was significantly lower than the control group (P<0.05). During the thrombolysis process, the adverse reactions in the study group and control group were 20% and 22%, respectively, with no significant difference between the two groups (P>0.05).

The clinical efficacy of edaravone and dexborneol combined with alteplase in the treatment of acute cerebral infarction is better than that of alteplase alone, and does not increase the risk of thrombolytic therapy.

Based on real world data and machine learning technology, a predictive model of progression free survival (PFS) of patients with breast cancer treated with lapatinib was constructed.

A retrospective collection of 150 patients admitted to the Fudan University Shanghai Cancer Center from July 2016 to June 2017 was conducted. The outcome indicator of the prediction model was whether the patient’s PFS was ≤ 1 year. Using sequential forward selection algorithms for feature selection, and comparing the predictive performance of 9 algorithms for building models, including extreme gradient boost (XGBoost), classification boost (CatBoost), random forest (RF), light gradient boost (LightGBM), gradient boost decision tree (GBDT), logistic regression (LR), support vector regression (SVR), artificial neural network (ANN), and TabNet.

Important variables included medication regimen, age, frequency of chemotherapy, anthracycline drugs, platinum drugs, estrogen receptor, disease stage, and number of metastatic sites. The XGBoost model had the best prediction performance, with a prediction accuracy of 93% and a recall rate of 87% for PFS≤1 year. And a prediction accuracy was 71%, and a recall rate was 83% for PFS > 1 year.

The performance and robustness of the prognosis prediction model for patients with breast cancer treated with lapatinib established are good, which can provide a better auxiliary decision-making basis for clinical treatment of breast cancer.

To explore the clinical characteristics of levosimendan-induced arrhythmia, analyze the possible risk factors, and establish a prediction model.

Clinical data of 643 discharged patients treated with levosimendan in a 3rd Grade Class A hospital from October 2020 to June 2022 were retrospectively collected and the time and type of arrhythmia were analyzed. Logistic regression analysis and ROC curve analysis were used to construct and evaluate the prediction model. Clinical data from another 69 patients were collected to verify the accuracy of the model.

Among 643 discharged patients, 94 cases (14.6%) had arrhythmias, of which 82 cases (87%) occurred during infusion and 2 days after infusion, and atrial fibrillation (32%) was the most common. Multivariate logistic regression analysis showed that the lowest blood potassium within 5 days after medication, left ventricular end-diastolic diameter (LV), and micropump velocity > 0.2 μg·kg^-1·min^-1 were independent risk factors for levosimendan-induced arrhythmia (all P<0.05), with the prediction model formula logit (P) =2.821-0.873× lowest serum potassium within 5 days after medication (0: >3.89mmol·L^-1; 1:≤3.89 mmol·L^-1) +0.697×LV (0:≤55 mm; 1: > 55 mm) -1.054× micropump speed >0.2 μg·kg^-1·min^-1 (0: no; 1: yes).When the cutoff value of logit (P) was 0.91, the area under the ROC curve was 0.672 (95% confidence interval: 0.627 to 0.715, P<0.001). The accuracy of the internal verification prediction model was 83%.

The incidence of arrhythmia induced by levosimendan is high, and ECG monitoring should be strengthened within 2 days after infusion. Blood potassium and micropump speed within 5 days after medication are controllable factors, and intervention should be strengthened to reduce the incidence of arrhythmia.

To establish a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of blood drug concentrations of nirmatrelvir and ritonavir in human plasma and apply it to therapeutic drug monitoring (TDM).

Plasma samples were precipitated, and the mobile phase consisted of 0.1% formic acid aqueous solution (phase A) and acetonitrile (phase B). Isocratic elution was used with a flow rate of 0.3 mL·min^-1, a column temperature of 40 ℃, and an EC-C18 chromatographic column. Multiple reaction monitoring was conducted in positive ion mode.

The ion channels used for quantitative analysis were m/z 500 → 110 (nirmatrelvir), m/z 721.2 →296.3 (ritonavir), and m/z 614.4 → 421 (internal standard remdesivir). In human plasma, nirmatrelvir showed good linearity in the range of 0.01 to 10 µg·mL^-1, while ritonavir exhibited good linearity in the range of 0.01 to 2.0 µg·mL^-1. The extraction recoveries were 79.56% to 89.91% for nirmatrelvir and 82.03% to 89.56% for ritonavir. The RSD values for intra-day and inter-day precision were all less than 15%, and the stability was satisfactory. The developed method was applied to measure the blood drug concentrations of 34 patients after oral administration of Paxlovid, which ranged from 1.04 to 18.0 µg·mL^-1.

The HPLC-MS/MS method established in this study is rapid, highly sensitive, and accurate, and it can be applied to monitor the therapeutic drug concentration monitoring of COVID-19 patients after taking Paxlovid.

To explore the main active components, targets and pathways of anti-liver fibrosis of Mori fructus by network pharmacology and animal experiment, and to explore its potential mechanism of Mori fructus against liver fibrosis.

The main active components and corresponding targets of Mori fructus were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and the target information was converted into target gene by Uniprot database. The targets of inflammatory disease were predicted in OMIM database and GeneCards database, and the targets of inflammatory genes were obtained. The network diagram of component-target-pathway was constructed using Cytoscape 3.7.2 software. Protein protein interaction (PPI) network was constructed using the String database and Cytoscape 3.7.2 software, and Gene Ontology (GO) biological process analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Fifty Kunming mice were randomly divided into six groups, including normal group, model group and low, medium and high dose of total flavonoids from Mori fructus (75,150, 300 mg·kg^-1) groups. The liver fibrosis model of mice was induced by carbon tetrachloride, and the serum biochemical indexes and predicted inflammatory indexes were detected. The histopathological changes of liver were observed, and the expression of matrix metalloproteinase 9 (MMP9) protein in liver tissue was detected by immunohistochemical method.

The main anti-inflammation components of Mori fructus include cyanin, quercetin, morin and β-carotene.There were 80 potential anti-inflammatory targets, and the PPI network mainly includes interleukin (IL) -6, tumor necrosis factor (TNF), protein kinase B (AKT) 1, albumin (ALB), vascular endothelial growth factor (VEGFA) and MMP9 and other core targets. The pathways involved mainly include fluid shear stress and atherosclerosis, pathways in cancer, lipid and atherosclerosis, Janus kinase/signal transducer and activator of transcription (JAK-STAT), etc. Animal experimental results showed that compared with the normal group, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum, the contents of IL-6 and TNF-α in liver tissue as well as the expression of MMP9 protein in the model group were significantly increased (P < 0.01). Compared with the model group, the levels of ALT and AST in serum, the contents of IL-6 and TNF-α and the protein expression of MMP9 protein in liver tissue were decreased (P < 0.05) and the degree of liver injury was alleviated in different doses of total flavonoids from Mori fructus.

Mori fructus has anti-liver fibrosis effects on IL-6, TNF-α, MMP9 and other targets through active components such as anthocyanin and quercetin, which are mainly related to phosphoinositide 3 kinase (PI3K) /AKT, JAK-STAT, and other signaling pathways. Its mechanism of liver protection may be related to the reduction of inflammatory reaction and the down-regulation of the protein expression of MMP9.

To establish the rational clinical application standard of Tanreqing injection, providing reference for rational clinical application of Tanreqing injection.

Based on the drug instructions of Tanreqing injection and referring to the Basic Principles of Clinical Application of Traditional Chinese Medicine Injections, professional guidelines and relevant literatures, the rules for evaluating the rationality of clinical application of Tanreqing injection including 11 indicators such as indications, usage and dosage, and solvent selection were formulated. The analytic hierarchical model (AHM) method was used to evaluate and analyze 198 archived medical records of Tanreqing injection from January to December 2021 in our hospital.

The main problems in the unreasonable application of Tanreqing injection included the duration of treatment, indications, usage and dosage, drug combination, etc. Among the 198 cases, 24 cases (12.1%) had a medical record score ( MRS) ≥90，44 cases (22.2%) had a score of 80≤MRS < 90, 82 cases (41.5%) had a score of 60≤MRS < 80, and 48 cases (24.2%) had a score of MRS < 60.

The use of Tanreqing injection in our hospital is basically reasonable, but there are still some problems in terms of treatment course, usage and dosage, drug combination, indications, etc. The AHM method is simple and practical, which provides a new method for the evaluation of the drug rational application.