Objective To explore and evaluate the adverse drug events(ADE)signals of thromboembolic events induced by cisplatin and carboplatin,and to provide references for clinical safety and rational use of drugs.Methods The cisplatin-and carboplatin-related thromboembolic adverse events reports were collected from the U.S.FDA Adverse Event Reporting System(FAERS)database with the reporting time range from the first quarter of 2004 to the fourth quarter of 2023.Thromboembolic ADR signals were detected using the reporting odds ratio(ROR)method,the medicines and healthcare products regulatory agency(MHRA)method,and the Bayesian confidence propagation neural network(BCPNN)method at the SMQ level and preferred term(PT)level.Results A total of 1 959 cisplatin-related thromboembolism events and 2 524 carboplatin-related thromboembolism events were reported.In terms of gender composition,after excluding reports with unspecified gender,the ratio of male to female was 1.69∶1 for cisplatin and 0.65∶1 for carboplatin.For cisplatin,triple signals were generated at the"thromboembolic events"SMQ level as well as its sub-levels"venous thromboembolic events",and dual signals were generated at the"arterial thromboembolic events"sub-level.However,for carboplatin,dual signals were generated at the"thromboembolic events"SMQ level,and three signals were generated only at the"venous thromboembolic events"sub-level.The PT hierarchy analysis of thromboembolic events revealed that except for"thrombotic microangiopathy"produced single signal,signals generated by cisplatin were all triple signals,among which"aortic thrombosis"(ROR 95%CI lower limit=72.59,IC-2SD=5.93)exhibited the strongest signal intensity.Different from cisplatin,except for"acute myocardial infarction","ischemic stroke",and"cerebral infarction",which generated dual signals,"aortic thrombosis",which generated a single signal,all the other signals produced by carboplatin were triple signals.Additionally,"venous occlusive liver disease"(ROR 95%CI lower limit=11.58,IC-2SD=3.35)displayed the strongest signal intensity.Among various types of thromboembolic events,both cisplatin-and carboplatin-related"pulmonary embolism"and"deep vein thrombosis"were reported the highest number,ranking first and second,respectively.Conclusions In this study,cisplatin and carboplatin were proven to increase the risk of thromboembolic adverse events.Cisplatin was associated with potential risks of"venous thromboembolism"and"arterial thromboembolism",while carboplatin was associated with"venous thromboembolism".Therefore,attention should be paid to the above risks during clinical use.

Objective To explore and evaluate the adverse drug events(ADE)signals of thromboembolic events induced by cisplatin and carboplatin,and to provide references for clinical safety and rational use of drugs.Methods The cisplatin-and carboplatin-related thromboembolic adverse events reports were collected from the U.S.FDA Adverse Event Reporting System(FAERS)database with the reporting time range from the first quarter of 2004 to the fourth quarter of 2023.Thromboembolic ADR signals were detected using the reporting odds ratio(ROR)method,the medicines and healthcare products regulatory agency(MHRA)method,and the Bayesian confidence propagation neural network(BCPNN)method at the SMQ level and preferred term(PT)level.Results A total of 1 959 cisplatin-related thromboembolism events and 2 524 carboplatin-related thromboembolism events were reported.In terms of gender composition,after excluding reports with unspecified gender,the ratio of male to female was 1.69∶1 for cisplatin and 0.65∶1 for carboplatin.For cisplatin,triple signals were generated at the"thromboembolic events"SMQ level as well as its sub-levels"venous thromboembolic events",and dual signals were generated at the"arterial thromboembolic events"sub-level.However,for carboplatin,dual signals were generated at the"thromboembolic events"SMQ level,and three signals were generated only at the"venous thromboembolic events"sub-level.The PT hierarchy analysis of thromboembolic events revealed that except for"thrombotic microangiopathy"produced single signal,signals generated by cisplatin were all triple signals,among which"aortic thrombosis"(ROR 95%CI lower limit=72.59,IC-2SD=5.93)exhibited the strongest signal intensity.Different from cisplatin,except for"acute myocardial infarction","ischemic stroke",and"cerebral infarction",which generated dual signals,"aortic thrombosis",which generated a single signal,all the other signals produced by carboplatin were triple signals.Additionally,"venous occlusive liver disease"(ROR 95%CI lower limit=11.58,IC-2SD=3.35)displayed the strongest signal intensity.Among various types of thromboembolic events,both cisplatin-and carboplatin-related"pulmonary embolism"and"deep vein thrombosis"were reported the highest number,ranking first and second,respectively.Conclusions In this study,cisplatin and carboplatin were proven to increase the risk of thromboembolic adverse events.Cisplatin was associated with potential risks of"venous thromboembolism"and"arterial thromboembolism",while carboplatin was associated with"venous thromboembolism".Therefore,attention should be paid to the above risks during clinical use.

Cancer is a severe threat to human life and health.The over-activation of oncogenes is the main reason for poor treatment and prognosis of cancer patients.Most of these over-activated oncogenes are protein tyrosine kinase(PTK).Among many PTKs,non-receptor tyrosine kinase(NRTK)is an important signaling molecule that regulates cell proliferation and migration as the primary driver of intracellular signaling pathway transduction.Targeting NRTK has become the focus and difficulty in developing anti-tumor drugs.Traditional Chinese medicine(TCM),with its characteristics of multi-channel,multi-link,multi-target,and low toxicity,plays a significant advantage in treating adjuvant tumors.So far,it has been found various traditional TCM monomers can inhibit NRTK from playing an anti-tumor role.This review summarized the part of Src,Jak,Abl,Fak families,the prominent members of NRTK in tumor progression,as well as the TCM monomers acting on these members.We aimed to provide a theoretical basis for the anti-tumor therapy targeting NRTK and a reference for the search for TCM monomer inhibitors of NRTK.

Tumor-associated macrophages (TAMs), a crucial component of the tumor microenvironment (TME), are closely associated to the growth, invasion, metastasis, and prognosis of breast cancer. Targeting TAMs is considered to be a potential new strategy for improving the therapeutic efficacy of breast cancer. TAMs interact with breast cancer cells and influence the development and progression of various breast cancer subtypes through multiple pathways, including the secretion of proteins, cytokines, chemokines, and exosomes. Anti-breast cancer drugs targeting TAMs and emerging therapies are continually being discovered. This article explores the effects and mechanisms of TAMs in different breast cancer subtypes, examines the anti-breast cancer effects of herbal extracts and their active ingredients targeting TAMs, and introduces new technologies such as nano-agents, gene therapy, and immunocellular therapy that target TAMs. These therapeutic strategies targeting TAMs may be critical in improving the therapeutic efficacy and prognosis of breast cancer patients.
Humans ; Breast Neoplasms/pathology* ; Female ; Tumor-Associated Macrophages/drug effects* ; Tumor Microenvironment/drug effects* ; Animals ; Molecular Targeted Therapy/methods*

Objective To investigate the effects and potential mechanisms of Marsdeniae Tenacissimae Caulis(Tongguanteng)injection and extract in human osteosarcoma cells proliferation,migration,invasion,and apoptosis.Methods MNNG/HOS,Saos-2 osteosarcoma cells,and normal bone marrow mesenchymal stem cells(BMSC)were cultured in vitro.Cells were incubated with different concentrations of Tongguanteng injection and Tongguanteng extract(40,60,80 mg/mL).Cell proliferation was evaluated by CCK-8 assay and plate colony formation assay.Cell migration and invasion were evaluated by scratch assay and Transwell assay.Cell apoptosis was evaluated by Hoechst33342 staining and Annexin-V/PI double staining assay.Bax,Bcl-2 and Caspase-3 mRNA expression were detected using RT-qPCR.The protein expressions of JAK1,p-JAK1,STAT3,p-STAT3 and MMP9 were detected by Western blot.Results Compared with the control group,both Tongguanteng injection and extract significantly decreased the survival rate of MNNG/HOS and Saos-2 cells,inhibited cell clone formation,migration,and invasion,induced cell apoptosis(P<0.05,P<0.01),promoted Bax mRNA and protein expression,inhibited Bcl-2 mRNA and protein expression,and up-regulated Caspase-3 mRNA and Cleaved Caspase-3 protein expression.Tongguanteng injection could significantly down-regulate the expressions of p-JAK1,p-STAT3 and MMP9 protein expression in Saos-2 cells(P<0.05,P<0.01).Conclusion Both Tongguanteng injection and Tongguanteng extract can significantly inhibit proliferation,migration and invasion of human osteosarcoma MNNG/HOS and Saos-2 cells,and induce apoptosis,with no significant difference in anti-tumor effect.The mechanism may be related to the inhibition of the activation of JAK1/STAT3 signaling pathway.

OBJECTIVE To mine the safety signals of FOLFOX scheme and FOLFIRI scheme-induced hepatotoxicity， and to provide reference for the selection of clinical rational treatment plan and the prevention and treatment of drug adverse reaction （ADR）. METHODS Reporting odds ratio method and proportion report ratio method were used to analyze adverse drug event （ADE） reports of FOLFOX scheme and FOLFIRI scheme in FDA adverse event reporting system during January 1， 2004-June 30， 2022. The potential safety signals of FOLFOX scheme and FOLFIRI scheme-induced hepatotoxicity were mined. RESULTS The amounts of ADE reports related to FOLFOX scheme and FOLFIRI scheme were respectively 3 454 and 1 359； the proportions of male and female patients involved were 1.50∶1 and 1.67∶1 in these two schemes， respectively. The top five countries with the largest number of reports were the United States， Japan， France， Italy and the United Kingdom， respectively accounting for 58.48% and 53.79% of the total reported cases. More than 90% of patients took no more than 5 drugs in combination， the proportion of patients receiving FOLFOX scheme and FOLFIRI scheme combined with anti-angiogenic drugs or epidermal growth factor receptor inhibitors was 45.45% and 86.82%， respectively. Totally 443 ADE reports of FOLFOX scheme-induced hepatotoxicity were collected， and 22 ADR signals were generated， including hepatic sinusoidal obstruction syndrome， nodular regenerative hyperplasia， drug-induced liver injury， blood bilirubin increased， etc. Totally 128 ADE reports of FOLFIRI scheme- induced hepatotoxicity were reported， and 9 ADR signals were generated， including blood bilirubin increased， hepatotoxicity， steatohepatitis， hepatic steatosis， etc. CONCLUSIONS FOLFOX scheme and FOLFIRI scheme can cause different types of hepatotoxicity. Clinical drug monitoring should be strengthened to guarantee drug safety.

Objective To analyze the main active components and potential molecular mechanism of Sophora flavescens against breast cancer based on network pharmacology and molecular docking. Methods The chemical constituents were collected and screened by TCMSP, ETCM database and literature review. The targets of active ingredients were predicted by Swiss Target Prediction database. Breast cancer-related targets were collected by GeneCards, TTD, Drugbank and OMIM. The anti-breast cancer targets of Sophora flavescens were screened by Venny 2.1.0 software. Cytoscape software was used to construct the network diagram of Sophora flavescens-key active ingredients-targets. STRING database was used to analyze the common targets, and PPI network diagram was constructed. GO function enrichment analysis and KEGG pathway enrichment analysis of key target proteins were performed by DAVID database and Hiplot online platform. Schrodinger software was used to calculate the molecular docking between the active ingredients and targets. Molecular biological methods were used to verify the key targets. Results A total of 36 active components with clear structures were screened from Sophora flavescens. 70 anti-breast cancer targets of Sophora flavescens were screened out. 12 core targets including EGFR, AKT1, ESR1, SRC, CYP19A1, AR and ABCB1 participate in endocrine resistance, EGFR tyrosine kinase inhibitors and estrogen signaling pathways in breast cancer. Moreover, the docking score between the core component and the key target AR is the highest. In vitro experiments showed that the extract of Sophora flavescens can inhibit the proliferation of breast cancer cells, induce cell apoptosis and up-regulate AR protein expression. Conclusion It was revealed that Sophora flavescens plays an anti-breast cancer role by regulating complex biological processes through multiple components acting on multiple targets and signaling pathways. The upregulation of AR protein by Sophora flavescens may become a new therapeutic strategy for the treatment of breast cancer.

In order to explore a suitable pathway for the scientific and technological achievement transformation at prefecture-level public hospitals, in October 2020, a prefecture-level tertiary hospital carried out the " 3+ 3+ 3" mode for scientific and technological innovation and achievement transformation. A three-level management structure was established, consisting of the ministry of science and education, the working group on the transformation of scientific and technological achievements, and the leading group. Three management systems were improved and formulated, including the " measures for reimbursement and rewards of scientific and technological achievements ", the " measures for intellectual property management", and the " implementation plan for promoting the transfer and transformation of scientific and technological achievements". The management measures for the three stages of intellectual property protection, incubation of scientific and technological achievements, and transfer and transformation of achievements were improved. These measures provided organizational support, institutional support, and feasible paths for this practice. After nearly three years of practice, hospitals had reduced the number of low-quality patent applications, and the number and amount of scientific and technological achievements transformed increased from 1 achievement and 10 000 yuan in 2020 to 9 achievements and 320 000 yuan in 2022. This exploration could provide a reference for the transfer and transformation of professional scientific and technological achievements in prefecture-level public hospitals in China.

Paclitaxel is the first-line chemotherapy drug for a variety of cancers. However， the paclitaxel resistance greatly reduced the efficacy in the later treatment stage， which seriously increased the mortality and recurrence rate of cancer and limited the clinical application of paclitaxel. At present， Chinese medicine compound prescription， proprietary Chinese medicine， and Chinese medicine injection are widely used as the adjuvant chemotherapy drugs for the treatment of cancer in clinic. Chinese medicine has shown unique advantages in improving the efficacy of chemotherapy drugs and the prognosis of chemotherapy， and reducing the toxic and side effects. However， the specific mechanism and effective monomer composition of Chinese medicine for reversing the resistance of chemotherapy drugs are unclear， and the application of Chinese medicine in different types of cancer is also limited， which are worthy of further exploration. This review summarized the composition of Chinese medicine monomer with synergistic antitumor effect combined with paclitaxel in recent years. The specific mechanism and pharmacological activities of Chinese medicine monomer reversing paclitaxel resistance were classified. This review found that through acting on the membrane transport protein， Chinese medicine monomer promoted the accumulation of paclitaxel in tumor cells， inhibited the expressions of protein and metabolic enzyme related to multidrug resistance and the metabolism of paclitaxel， and regulated the levels of apoptosis genes and factors and apoptosis-related pathways to promote the inhibitory effect of paclitaxel on cell proliferation. Chinese medicine monomer also significantly improved paclitaxel chemotherapy sensitivity by regulating the expression levels of micro ribonucleic acid （microRNA） and long non-coding ribonucleic acid RNA （lncRNA）， inhibiting the characteristics of tumor stem cells and tumor metabolic reprogramming， improving tumor microenvironment， and triggering tumor cell death autophagy and oxidative stress response. This review provides a theoretical basis for clarifying the specific anti-tumor mechanism of Chinese medicine monomer combined with paclitaxel， which is of great significance for the development of new Chinese medicine and the clinical research of the drugs combined with paclitaxel， and has certain value for the application of Chinese medicine combined with other chemotherapy drugs.

Side effects from targeted drugs remain a serious concern.One reason is the nonselective binding of a drug to unintended proteins such as its paralogs,which are highly homologous in sequences and have similar structures and drug-binding pockets.To identify targetable differences between paralogs,we analyzed two types (type-Ⅰ and type-Ⅱ) of functional divergence between two paralogs in the known target protein receptor family G-protein coupled receptors (GPCRs) at the amino acid level.Paralogous protein receptors in glucagon-like subfamily,glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R),exhibit divergence in ligands and are clinically validated drug targets for type 2 diabetes.Our data showed that type-Ⅱ amino acids were significantly enriched in the binding sites of antagonist MK-0893 to GCGR,which had a radical shift in physicochemical properties between GCGR and GLP-1R.We also examined the role of type-Ⅰ amino acids between GCGR and GLP-1R.The divergent features between GCGR and GLP-1R paralogs may be helpful in their discrimination,thus enabling the identification of binding sites to reduce undesirable side effects and increase the target specificity of drugs.