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.

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 explore the mechanism of Marsdenia tenacissima in the treatment of breast cancer through network pharmacology and experimental verification.Methods Literature retrieval was conducted to obtain the active components of Marsdenia tenacissima.The SwissTargetPrediction database was used to predict the potential targets of these active components.Targets of breast cancer were obtained from GeneCards,GEPIA2,OMIM,PharmGKB and TTD databases.The intersection targets were obtained,and a Marsdenia tenacissima-breast cancer-targets network was constructed using Cytoscape 3.9.0 software.The core targets were identified through protein-protein interaction(PPI)network analysis,followed by GO and KEGG pathway enrichment analysis to screen relevant signaling pathways.Molecular docking validation was performed for the top 10 key targets and major active components.The human breast cancer cell line MDA-MB-231 was treated with Marsdenia tenacissima injection in vitro.Cell proliferation ability was detected by CCK-8 assay and colony formation assay.Cell apoptosis was detected by Calcein-AM/PI staining and flow cytometry.Cell migration ability was detected by Transwell assay.Western blot experiment was used to validate the PI3K-AKT signaling pathway.Results Totally 37 active components and 276 potential targets against breast cancer were screened from Marsdenia tenacissima,including 11alpha-O-Benzoyl-12beta-O-acetyl tenacigenin B,Caffeic acid,Drevogenin A and Kaempferol.25 core targets were screened by PPI network such as AKT1,EGFR,TNF,CTNNB1 and IL-6,which mainly affected the estrogen signaling pathway,ErbB signaling pathway,HIF-1 signaling pathway and PI3K-AKT signaling pathway,etc.The molecular docking results showed that the main active components of Marsdenia tenacissima exhibited good binding activities with the core targets AKT1,ALB,CASP3,ESR1 and TNF.The results of in vitro experiments showed that Marsdenia tenacissima injection could inhibit the proliferation and migration ability of MDA-MB-231 cells(P<0.01,P<0.001)and induce apoptosis(P<0.001),as well as inhibit the activation of PI3K-AKT signaling pathway(P<0.05,P<0.01).Conclusion Marsdenia tenacissima may exert its anti-breast cancer effects through multiple targets and pathways,and the mechanism may be related to the inhibition of PI3K-AKT signaling pathway.

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 evaluate the effectiveness， safety and economics of Aidi injection combined with first-line chemotherapy for non-small cell lung cancer （NSCLC）， and to provide evidence-based reference for clinical drug use and decision. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang databases， VIP and Health Technology Assessment （HTA） related websites， HTA reports， systematic evaluation/meta-analysis and economic evaluations about Aidi injection combined with first-line chemotherapy for NSCLC were collected from the inception to Aug. 2022. After data extraction and quality evaluation， descriptive analysis was performed for the results of included studies. RESULTS A total of 16 pieces of literature were included， involving 1 piece of systematic review， 13 pieces of meta-analysis， 2 pieces of pharmacoeconomic studies. Compared with first-line chemotherapy， Aidi injection combined with first-line chemotherapy could improve response rate and disease control rate， prolonged survival time， improved survival quality， reduced the incidence of nausea and vomiting， leukocytopenia and thrombocytopenia， and improved immune function， but had controversial effects on liver and kidney function. With the payment threshold set by 3 times the national per capita GDP in 2019， Aidi injection combined with first-line chemotherapy had a more economical probability. CONCLUSIONS Aidi injection combined with first-line chemotherapy for NSCLC has good efficacy and safety， and has certain economic benefits. However， given the limited pharmacoeconomic studies included， the economic conclusions obtained need to be carefully interpreted.

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.

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.

OBJECTIVE：To provide reference for pharmacists ’participation in the integrated outpatient treatment in China. METHODS：Using“Pharmacist”“Clinical pharmacist ”“Integrated outpatient ”“Combined outpatient ”“Outpatient department ”as Chinese and English retrieval words ，the related literatures were retrieved from Embase ，PubMed，CNKI，Wanfang and VIP ， retrieval time limit was from the construction of database to July 24，2019. The type ，research method ，service content and the evaluation indexes of the service effectiveness of pharmacists ’participation in the integrated outpatient treatment at home and abroad were compared. RESULTS ：A total of 848 related literatures were retrieved ，including 30 valid ones. From respective of research method ，main foreign method was retrospective research （42.86％），followed by self-control trial （21.43％） and questionnaire survey/telephone research （14.29％）；main domestic method was descriptive research （37.50％），followed by case control（25.00％）and self-control trial （25.00％）. From respective of the types of pharmacists ’participation in the integration of outpatient services ，there were 9 types of pharmacists ’participation in the foreign integrated outpatient treatment ，including cancer or palliative outpatient department ，geriatric outpatient department ，lipid management outpatient department ，AIDS outpatient department， hypertension outpatient department ， etc. Among them ， the proportion of pharmacists participating in cancer orpalliativeoutpatient department was the highest ，being 42.86％. There were 11 types of pharmacists ’participation in the domestic integrated outpatient treatment ， including anticoagu lation （No.ZYCC2019017） outpatient department ， diabetes outpatient department and epilepsy out patient department ，Parkinson’s disease outpatient 38297155。E-mail：lydaishu@163.com department， etc. Foreign pharmacists provided in-depthservices in cancer or palliative outpatient department ， including treatment suggestions ，classification and resolution of drug-related problems ，provision of drug information and pharmacist intervention ，etc.；the contents of pharmaceutical care provided by domestic pharmacists in anticoagulant outpatient department was more in-depth ，including dosage adjustment of anticoagulants，pharmaceutical care ，medication consultation ，medication guidance and education ，etc. For the evaluation of service effect，foreign researches involved 13 kinds of outcome indexes ，including the improvement of clinical indexes ，the reduction of medical cost ，reduction of drug used ，etc. Domestic researches involved 11 kinds of outcome indexes ，including the improvement of medication compliance ，clinical indexes and ADR ，etc. CONCLUSIONS ：The participation of pharmacists in integrated outpatient at home and abroad are mainly chronic diseases ，but also different in their emphasis . The domestic pharmacists and related scholars can improve the research methods ，the types of integrated outpatient services ，service contents and the evaluation indexes of effectiveness of pharmacists.

Objective To investigate the mechanism of Qinggan-Huoxue recipe in the treatment of alcoholic liver disease by observing its function on alcoholic liver disease rat fibroblast growth factor -21 (FGF21). Methods The rats were randomly divided into the blank group (n=10), the carbon tetrachloride group (n=10), the model group (n=11), the Qinggan-Huoxue recipe group (n=10), the Qinggan recipe group (n=9) and the Huoxue recipe group (n=10). Except for the blank group and the carbon tetrachloride group, the other rats were given 10 ml/kg alcohol, corn oil and pyrazole mixture (4.5 ml: 2 ml: 25 mg), once a day, 0.3 ml/kg carbon tetrachloride olive oil solution (carbon tetrachloride: olive oil =1: 3) intraperitoneally, and twice a week for 12 weeks to prepare the alcoholic liver disease model. In the ninth week, the Qinggan-Huoxue recipe group was treated with 4.75 g/kg of Qinggan-Huoxue recipe, the Qinggan recipe group was treated with 1.5 g/kg of Qinggan recipe, and the Huoxue recipe group was treated with 3.25 g/kg of Huoxue recipe, once a day, and 28 d for continuous administration. The pathological changes of liver tissue were observed by HE staining and Masson staining. The serum levels of AST and ALT were detected in rats. The changes of FGF21 protein and mRNA expression were detected by immunohistochemistry, Western blotting and fluorescence quantitative PCR. Results Compared with the model group, the liver weight and liver body ratio in the Qinggan recipe group, Qinggan-Huoxue recipe group and Huoxue recipe group were significantly lower (P<0.01). Compared with the model group, the serum ALT (41.95 ± 26.78 U/L, 46.63 ± 21.00 U/L, 37.57 ± 27.85 U/L vs. 138.34 ± 43.35 U/L), AST (102.74 ± 23.55 U/L, 111.50 ± 21.26 U/L, 83.72 ± 37.57 U/L vs. 257.41 ± 162.31 U/L) in the Qinggan recipe group, Qinggan-Huoxue recipe group and Huoxue recipe group significantly decreased (P<0.01 or P<0.05). Compared with the model group, the expression of FGF21 protein (1.19 ± 0.07, 1.24 ± 0.12 vs. 0.92 ± 0.04) in Qinggan recipe group and Qinggan-Huoxue recipe group significantly increased (P<0.05), and the expression of FGF21 mRNA (1.25 ± 0.08 vs. 0.95 ± 0.05) in Qinggan-Huoxue recipe group significantly increased (P<0.05). Conclusions FGF21 plays an important role in the alcoholic liver disease. During the process of liver injury, FGF21 increases continuously. Qinggan-Huoxue recipe can improve the content of FGF21 in the treatment of alcoholic liver disease.

Objective: To investigate the entry points of traditional Chinese clinical pharmacists participating in multidisciplinary team (MDT) to provide reference for more peers and subject development. Methods: According to the daily work of traditional Chi-nese clinical pharmacists in joint multidisciplinary clinic and combining with patients' medication characteristics, traditional Chinese clinical pharmacists carried out works from three aspects including doctors, patients and peers. Results: After the medication was guided by traditional Chinese clinical pharmacists, the effect of medicinal treatment was improved, the patients' medication compliance increased and the incidence of adverse reactions was reduced. Moreover, it brought more ideas to the peers within the discipline in our hospital. Conclusion: Traditional Chinese clinical pharmacists can exploit their advantages to the full to find clinical demands and more entry points in works. At the same time, traditional Chinese clinical pharmacists should enhance related knowledge, professional qualities, and cooperation and communication ability comprehensively.