This study was to build a canine portal hypertension model by intra-portal administration of high polymer material polyurethane and organic solvent tetrahydrofuran mixed solutions in order to evaluate the effectiveness of the model. Twelve local crossbreed dogs were selected randomly, with intra-portal administration of 8% (weight/volume) polyurethane- tetrahydrofuran solutions through an incision in the upper abdomen to build the portal hypertension model. We measured the portal vein pressure before modeling, during modeling, and four-, eight-, and twelve- weeks after modeling, respectively. Then we evaluated the effectiveness of the model comparing values of data with those data obtained before modeling started, which were regarded as the normal values. The results showed that the portal vein pressure rose by 2. 5 times after the solution administrated instantly as much as that before modeling, and maintained at 1. 5 times after 4 weeks. This method presents an easy operation, low animal mortality and reliable model of portal hypertension. Its less abdominal adhesions and its ability in keeping normal anatomic structure specially make it suit for surgical research of portal hypertension.
Animals ; Disease Models, Animal ; Dogs ; Furans ; adverse effects ; Hypertension, Portal ; Polyurethanes ; adverse effects ; Portal Vein ; physiopathology

In this study, chemistry, biology and pharmacology were combinated to screen pseudoallergenic substances of Shuang-huanglian injection (SHLI) so that to establish a scientific and systematic approach to screen pseudoallergenic substances of traditional Chinese medicine injections. The mouse pseudoallergic reaction models were used to screen the pseudoallergic reaction of SHLI's intermediate extract and the intermediate extract's component or ingredient. Among the three intermediates of Shuanghuanglian injection (extract of Scutellaria baicalensis, extract of Lonicera japonica, extract of Forsythia suspensa) , pseudoallergic action of Forsythia suspensa was the strongest, Forsythia suspesnsa's pseudoallergic reaction mainly associated with the composition with largerchemical polarity. Further it was found that forsythiaside A and arctiin which existed in the the composition with largerchemical polarity caused obvious pseudoallergic reactions. SHLI with removal forsythoside A with the technology of HPLC-MS displayed reduced pseudoallergic reaction and a significant improved safety. This study provided a scientific basis for SHLI process improvements and also offered idea and research foundation for screening pseudoallergenic substances injections in other TCM injections.
Animals ; Drug Hypersensitivity ; etiology ; Drugs, Chinese Herbal ; adverse effects ; analysis ; Furans ; adverse effects ; Glucosides ; adverse effects ; Glycosides ; adverse effects ; Injections ; Male ; Mice ; Mice, Inbred ICR

Objective: To explore the efficacy and safety of real-world eribulin in the treatment of metastatic breast cancer. Methods: From December 2019 to December 2020, patients with advanced breast cancer were selected from Beijing Chaoyang District Sanhuan Cancer Hospital, Shandong Cancer Hospital, Peking University Cancer Hospital, Baotou Cancer Hospital, Shengjing Hospital Affiliated to China Medical University, and Cancer Hospital of Chinese Academy of Medical Sciences. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: The median progression-free survival (PFS) of 77 patients was 5 months, the objective response rate (ORR) was 33.8%, and the disease control rate (DCR) was 71.4%. The ORR of patients with triple-negative breast cancer was 23.1%, and the DCR was 57.7%; the ORR of patients with Luminal breast cancer was 40.0%, and the DCR was 77.8%; the ORR of patients with HER-2 overexpression breast cancer was 33.3%, and the DCR was 83.3%. ORR of 50.0% and DCR of 66.7% for patients treated with eribulin as first to second line treatment, ORR of 29.4% and DCR of 76.5% for patients treated with third to fourth line and ORR of 28.6% and DCR of 71.4% for patients treated with five to eleven line. The ORR of patients in the eribulin monotherapy group was 40.0% and the DCR was 66.0%; the ORR of patients in the combination chemotherapy or targeted therapy group was 22.2% and the DCR was 81.5%. Patients with a history of treatment with paclitaxel, docetaxel, or albumin paclitaxel during the adjuvant phase or after recurrent metastasis had an ORR of 32.9% and a DCR of 69.9% when treated with eribulin. The treatment efficacy is an independent prognostic factor affecting patient survival (P<0.001). The main adverse reactions in the whole group of patients were Grade Ⅲ-Ⅳ neutrophil decline [29.9% (23/77)], and other adverse reactions were Grade Ⅲ-Ⅳ fatigue [5.2% (4/77)], Grade Ⅲ-Ⅳ peripheral nerve abnormality [2.6% (2/77)] and Grade Ⅲ-Ⅳ alopecia [2.6% (2/77)]. Conclusions: Eribulin still has good antitumor activity against various molecular subtypes of breast cancer and advanced breast cancer that has failed multiple lines of chemotherapy, and the adverse effects can be controlled, so it has a good clinical application value.
Breast Neoplasms/pathology* ; Female ; Furans/adverse effects* ; Humans ; Ketones/adverse effects* ; Paclitaxel/adverse effects* ; Treatment Outcome ; Triple Negative Breast Neoplasms/drug therapy*

OBJECTIVETo study the effect of arctiin on mouse podocyte epithelial-mesenchymal transition (EMT) induced by advanced oxidation protein products (AOPP).

METHODSMouse podocytes were stimulated by 200 µg/ml AOPP for 24 h in the presence of 50, 100, 200, and 400 µmol/L arctiin. The expressions of α-smooth muscle actin, Grp78 and CHOP were detected using Western blotting.

RESULTThe expressions of α-SMA, Grp78 and CHOP were inhibited by arctiin, showing a dose-dependent effect within a given range of arctiin concentration.

CONCLUSIONAOPP causes endoplasmic reticulum stress to induce EMT of mouse podocytes, and arctiin can decrease EMT by alleviating the stress. This finding sheds light on a new scope of research of renal fibrosis.

Actins ; metabolism ; Advanced Oxidation Protein Products ; adverse effects ; Animals ; Cell Line ; Endoplasmic Reticulum Stress ; drug effects ; Epithelial-Mesenchymal Transition ; drug effects ; Furans ; pharmacology ; Glucosides ; pharmacology ; Heat-Shock Proteins ; metabolism ; Mice ; Podocytes ; metabolism ; pathology ; Transcription Factor CHOP ; metabolism

OBJECTIVETo investigate the effect of arctiin on advanced oxidation protein product (AOPP)-induced epithelial-to-mesenchymal transition (EMT) in tubular cells and explore the mechanisms underlying this effect.

METHODSHuman proximal tubular cells (HK-2 cells) were treated with bovine serum albumin (BSA) or AOPPs in the presence or absence of arctiin. The expressions of E-cadherin, vimentin, and GRP78 at the protein and mRNA levels in the cells were examined using Western blotting and quantitative real-time PCR. The level of reactive oxygen species (ROS) was measured by flow cytometry with DCFH-DA as the fluorescent probe.

RESULTSCompared with BSA-treated cells, the cells treated with AOPPs showed decreased expression of epithelial cell marker E-cadherin and overexpression of mesenchymal marker vimentin and endoplasmic reticulum stress marker GRP78 with an increased ROS level. These changes induced by AOPPs were partly inhibited by arctiin.

CONCLUSIONArctiin can ameliorate AOPP-induced EMT in tubular cells by inhibiting endoplasmic reticulum stress, and oxidative stress response may participate in this process.

Advanced Oxidation Protein Products ; adverse effects ; Cadherins ; metabolism ; Cell Line ; Endoplasmic Reticulum Stress ; Epithelial Cells ; cytology ; drug effects ; Epithelial-Mesenchymal Transition ; Furans ; pharmacology ; Glucosides ; pharmacology ; Heat-Shock Proteins ; metabolism ; Humans ; Kidney Tubules ; cytology ; drug effects ; Oxidative Stress ; Reactive Oxygen Species ; metabolism ; Vimentin ; metabolism