Objective: To explore the mechanism of action of Zangjiangzhi capsule (ZJZC) in treating hyperlipidemia (HLP). Methods: The components of ZJZC were analyzed and identified using ultra-high performance liquid chromatography with Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS/MS). Network pharmacology analysis was used to explore the mechanism of action of ZJZC in HLP treatment. The SwissTargetPrediction database was used to predict compound targets, and GeneCards, DisGeNet, OMIM, and DRUGBANK databases were used to identify HLP-related targets. Protein–protein interaction diagrams were constructed using the STRING database. The targets were subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The “herb-ingredient-target” network was visualized using Cytoscape. Preliminary validation was performed using molecular docking and enzyme-linked immunosorbent assay. Results: Ninety compounds were identified in ZJZC, including 34 flavonoids, 12 phenols, 10 terpenoids, 10 alkaloids, 8 organic acids, 8 anthraquinones, and 9 other compounds. In total, 904 targets were identified for these compounds. Among them, 158 targets intersected with the HLP target network. Network pharmacology analysis showed that MAPK1, PPAR-α, RXRA, HSP90AA1, PIK3R1, AKT1, PIK3CA, IL6, TNF, and ESR1 are the key targets of action. KEGG enrichment analysis identified 164 pathways. Among these, the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis pathways, regulation of lipids in adipocytes, and insulin resistance are related to HLP. Molecular docking showed good affinity between the key targets and ingredients. Further, ZJZC treatment in mice resulted in lower expression of MAPK1 protein and increased expression of PPAR-α protein, which have been shown to be strongly associated with HLP. Conclusions This study showed that ZJZC contains various active ingredients and can modulate multiple targets and pathways associated with HLP, providing evidence at the molecular level for its clinical application in the treatment of HLP.

Objective:To study the effects and mechanisms of anlotinib on the proliferation,migration,invasion,and apoptosis of MYCN-amplified neuroblastomas(NB).Methods:Two MYCN-amplified NB cell lines were treated with varying concentrations of anlotinib.CCK8 and clone formation assays were employed to detect cell proliferation,flow cytometry was used to detect cell apoptosis,scratch tests were performed to determine cell migration,and Transwell assays were used to detect cell invasion.Results:CCK8 assays indicated that anlotinib inhibited proliferation in MYCN-amplified NB cell lines in a concentration-and time-dependent manner.Clone formation assays showed that anlotinib significantly inhibited cell clone formation(P<0.000 1).The results of the apoptosis experiment showed that anlotinib significantly promoted apoptosis in MYCN-amplified NB cell lines(P<0.000 1).Scratch assays showed that anlotinib significantly reduced the migration ability of MYCN-amplified NB cells(P<0.000 1).Transwell assays revealed that anlotinib significantly inhibited the invasive abilities of MYCN-amplified NB cell lines(P<0.000 1).Western blot analysis demonstrated that anlotinib significantly reduced the phosphorylation of VEGFR2 and AKT proteins in MYCN-amplified NB cells.The expression of the key downstream proteins N-cadherin and Bcl-2 was significantly down-regulated,whereas the expression of E-cadherin and Bax was significantly upregulated.Conclusions:Anlotinib markedly inhibits the prolifer-ation,migration,and invasion of MYCN-amplified NB cells and induces apoptosis via the VEGFR2/PI3K/AKT signaling pathway.

Objective:To study the effects and mechanisms of anlotinib on the proliferation,migration,invasion,and apoptosis of MYCN-amplified neuroblastomas(NB).Methods:Two MYCN-amplified NB cell lines were treated with varying concentrations of anlotinib.CCK8 and clone formation assays were employed to detect cell proliferation,flow cytometry was used to detect cell apoptosis,scratch tests were performed to determine cell migration,and Transwell assays were used to detect cell invasion.Results:CCK8 assays indicated that anlotinib inhibited proliferation in MYCN-amplified NB cell lines in a concentration-and time-dependent manner.Clone formation assays showed that anlotinib significantly inhibited cell clone formation(P<0.000 1).The results of the apoptosis experiment showed that anlotinib significantly promoted apoptosis in MYCN-amplified NB cell lines(P<0.000 1).Scratch assays showed that anlotinib significantly reduced the migration ability of MYCN-amplified NB cells(P<0.000 1).Transwell assays revealed that anlotinib significantly inhibited the invasive abilities of MYCN-amplified NB cell lines(P<0.000 1).Western blot analysis demonstrated that anlotinib significantly reduced the phosphorylation of VEGFR2 and AKT proteins in MYCN-amplified NB cells.The expression of the key downstream proteins N-cadherin and Bcl-2 was significantly down-regulated,whereas the expression of E-cadherin and Bax was significantly upregulated.Conclusions:Anlotinib markedly inhibits the prolifer-ation,migration,and invasion of MYCN-amplified NB cells and induces apoptosis via the VEGFR2/PI3K/AKT signaling pathway.

A 49-year-old female patient took febuxostat 20 mg once daily orally due to chronic kidney disease and hyperuricemia. On day 9 of medication, the patient developed facial hot flashes, and then purplish red maculopapules gradually appeared on the head, face, trunk, and both lower limbs. The rash were aggravated and spread gradually all over the body, involving the eyes, mouth, and vaginal mucosa. Lysis blisters appeared at the waist, and the area of epidermalysis was less than 10%. Laboratory tests showed white blood cell count 2.1×10 9/L, neutrophil count 1.7×10 9/L, hemoglobin 59 g/L, platelet count 97×10 9/L, C-reactive protein 105.6 mg/L; serum creatinine 1 062 μmol/L, and uric acid 647 μmol/L; human leukocyte antigen B*5801 allele was positive. Severe erythema multiforme induced by febuxostat was considered. Febuxostat was stopped immediately and treatments including protective isolation care, methylprednisolone, immunoglobulin, hemodialysis combined with hemoperfusion were given. On day 16 of treatments, black scab was found on the lip mucosa, and 30% skin scab peeled off. After 19 days of treatments, most of the scabs of whole body fell off, and new skin was visible. Laboratory tests showed that white blood cell count and platelet count returned to normal, C-reactive protein was 2.41 mg/L, serum creatinine was 582 μmol/L, and uric acid was 424 μmol/L.

The clinical data of a 64-year-old patient with adrenocortical adenoma complicated with inferior vena cava tumor thrombus(IVCTT) were retrospectively analyzed. The patient was admitted becourse of intermittent dizziness for 4 months. CT examination revealed right adrenal tumor, and IVCTT was found in operation. Adrenal cortical adenoma needs to be distinguished from adrenal cortical carcinoma pathologically. Preoperative color Doppler ultrasonography, CT angiography or inferior vena cava angiography can confirm the diagnosis of IVCTT and tumor thrombus grade, and different surgical methods should be selected according to tumor thrombus grade.

A 49-year-old female patient took febuxostat 20 mg once daily orally due to chronic kidney disease and hyperuricemia. On day 9 of medication, the patient developed facial hot flashes, and then purplish red maculopapules gradually appeared on the head, face, trunk, and both lower limbs. The rash were aggravated and spread gradually all over the body, involving the eyes, mouth, and vaginal mucosa. Lysis blisters appeared at the waist, and the area of epidermalysis was less than 10%. Laboratory tests showed white blood cell count 2.1×10 9/L, neutrophil count 1.7×10 9/L, hemoglobin 59 g/L, platelet count 97×10 9/L, C-reactive protein 105.6 mg/L; serum creatinine 1 062 μmol/L, and uric acid 647 μmol/L; human leukocyte antigen B*5801 allele was positive. Severe erythema multiforme induced by febuxostat was considered. Febuxostat was stopped immediately and treatments including protective isolation care, methylprednisolone, immunoglobulin, hemodialysis combined with hemoperfusion were given. On day 16 of treatments, black scab was found on the lip mucosa, and 30% skin scab peeled off. After 19 days of treatments, most of the scabs of whole body fell off, and new skin was visible. Laboratory tests showed that white blood cell count and platelet count returned to normal, C-reactive protein was 2.41 mg/L, serum creatinine was 582 μmol/L, and uric acid was 424 μmol/L.

Objective: To investigate the application of single-molecule PCR (SM-PCR) in the detection of plasma ctDNA for the treat-ment of patients with advanced lung adenocarcinoma. Methods: In total, 30 patients diagnosed with advanced lung adenocarcinoma were enrolled between June 2017 and May 2018. ctDNA fragments of the target genes (EGFR, KRAS, BRAF, ALK, HER2, and TP53) from the blood samples were enriched by SM-PCR, and DNA libraries were prepared. Finally, a high-throughput sequencing was performed. The EGFR detection of tumor tissue samples was performed using real-time fluorescence PCR based on the amplification refractory mutation system (ARMS) and consistency in the results of EGFR mutation detection in the plasma and tissue was compared. Results:The results of both the methods were consistent (Kappa=0.867, P<0.001). The McNemar's test also indicated that the results are not statistically different (P=0.500). Conclusions: SM-PCR can be used for the detection of plasma EGFR mutations. The target detection sites are more comprehensive and multiple mutations can be detected at the same time. Results of the analysis are more precise and can be absolutely quantified.

In recent years, the number of advanced non-small cell lung cancer (NSCLC) patients has gradually increased, and the treatment methods have also been significantly increased. However, there are no standard treatment plans at home and abroad for third-line and above patients who are refractory to targeted therapy epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) or chemotherapy. The clinical treatment effect is also not satisfactory. Anlotinib is a novel TKI targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit. ALTER0303 trail, phase III study has demonstrated that Anlotinib significantly prolonged overall survival (OS) and progression-free survival (PFS) in advanced NSCLC patients as 3rd line treatment.Here we report a case of advanced lung adenocarcinoma harboring KRAS mutation treated with Anlotinib.
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Adenocarcinoma ; drug therapy ; enzymology ; genetics ; pathology ; Adenocarcinoma of Lung ; Aged ; Antineoplastic Agents ; therapeutic use ; Humans ; Indoles ; therapeutic use ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; pathology ; Male ; Mutation ; Proto-Oncogene Proteins p21(ras) ; genetics ; metabolism ; Quinolines ; therapeutic use