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*

To systemically evaluate the efficacy and safety of Gingko Ketone Ester Dropping Pills in treating angina pectoris and co-ronary heart disease. CNKI, Wanfang, SinoMed, PubMed, Cochrane Library and EMbase databases were retrieved on computer, and the randomized clinical trial(RCT) on Gingko Ketone Ester Dropping Pills in treating angina pectoris and coronary heart disease, which were published from the database establishment to December 31, 2019, were comprehensively collected. Literature screening, data extraction and quality evaluation were conducted independently by two researchers according to inclusion and exclusion criteria. Literature methodology quality evaluation was conducted with use of the Cochrane Handbook 5.3.0(bias risk assessment tool). Meta-analysis was performed with RevMan 5.3.0 software. A total of 10 RCTs were included. The results of the Meta-analysis showed that as compared with conventional Western medicine alone, the application of Gingko Ketone Ester Dropping Pills combined with conventional Western medicine treatment further improved the total effective rate and electrocardiogram effect(RR=1.43,95%CI[1.20,1.71],P<0.000 1). There were statistically significant differences in the number of angina attacks, the duration of angina and the amount of nitroglycerin used. In terms of safety indicators, four studies reported adverse reactions in the experimental group, including facial flu-shing, tachycardia, dizziness, dyspnea, nausea and other symptoms. Based on the existing findings, in the treatment of angina pectoris and coronary heart disease, Gingko Ketone Ester Dropping Pills combined with conventional Western medicine can improve the clinical total effective rate, electrocardiogram effect, number of angina attacks, duration of angina and the amount of nitroglycerin used. However, in the included studies, due to some methodological quality problems which would impact the reliability of literature results more high-quality randomized controlled trials are still needed for further verification.
Angina Pectoris/drug therapy* ; Coronary Disease/drug therapy* ; Drugs, Chinese Herbal/adverse effects* ; Esters ; Ginkgo biloba ; Humans ; Ketones/adverse effects* ; Randomized Controlled Trials as Topic ; Reproducibility of Results

AIMTo search for new compounds with strong anti-inflammatory activity and low gastrointestinal (GI) side effects.

METHODSA series of p-(methanesulfonyl) styrene-linked cyclic ketone derivatives were synthesized. Their anti-inflammatory activities against xylene-induced mice ear swelling and carrageenan-induced rat paw edema were evaluated, and their GI side effects in the rats were examined.

RESULTSNine target compounds (ZA(1-9)) were obtained, and their structures were determined by IR, 1HNMR, MS and elemental analysis. Compared with controls diclofenac (DC) and rofecoxib (RC) , ZA(3, 5-9) showed no significant difference in anti-inflammatory activity against xylene-induced ear swelling in mice. ZA(3, 7, 8) showed potency comparable to DC and RC (P > 0.05) and ZA6 was more potent than DC and RC (P < 0.05) in the treatment of carrageenan-induced rat paw edema. ZA(3, 5-9) showed less GI side effects than DC (P < 0.05, P < 0.01) and no significant difference compared with RC (P > 0.05).

CONCLUSIONp-(Methanesulfonyl) styrene-linked cyclic ketone derivatives showed strong anti-inflammatory activity but few GI side effects and deserve to be further investigated.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; chemical synthesis ; chemistry ; Carrageenan ; Edema ; chemically induced ; drug therapy ; Ketones ; chemical synthesis ; chemistry ; Mice ; Peptic Ulcer ; drug therapy ; Rats ; Structure-Activity Relationship ; Styrenes ; chemical synthesis ; chemistry

BACKGROUND: To evaluate the clinical efficacy of three-level anterior cervical arthrodesis with polyethyletherketone (PEEK) cages and plate fixation for aged and osteoporotic patients with degenerative cervical spinal disorders. METHODS: Twenty one patients, who had undergone three-level anterior cervical arthrodesis with a cage and plate construct for degenerative cervical spinal disorder from November 2001 to April 2007 and were followed up for at least two years, were enrolled in this study. The mean age was 71.7 years and the mean T-score using the bone mineral density was -2.8 SD. The fusion rate, change in cervical lordosis, adjacent segment degeneration were analyzed by plain radiographs and computed tomography, and the complications were assessed by the medical records. The clinical outcomes were analyzed using the SF-36 physical composite score (PCS) and neck disability index (NDI). RESULTS: Radiological fusion was observed at a mean of 12.3 weeks (range, 10 to 15 weeks) after surgery. The average angle of cervical lordosis was 5degrees preoperatively, 17.6degrees postoperatively and 16.5degrees at the last follow-up. Degenerative changes in the adjacent segments occurred in 3 patients (14.3%), but revision surgery was unnecessary. In terms of instrument-related complications, there was cage subsidence in 5 patients (23.8%) with an average of 2.8 mm, and loosening of the plate and screw occurred in 3 patients (14.3%) but there were no clinical problems. The SF-36 PCS before surgery, second postoperative week and at the last follow-up was 29.5, 43.1, and 66.2, respectively. The respective NDI was 55.3, 24.6, and 15.9. CONCLUSIONS: For aged and osteoporotic patients with degenerative cervical spinal disorders, three-level anterior cervical arthrodesis with PEEK cages and plate fixation reduced the pseudarthrosis and adjacent segment degeneration and improved the clinical outcomes. This method is considered to be a relatively safe and effective treatment modality.
Aged ; Aged, 80 and over ; Biocompatible Materials ; *Bone Plates/adverse effects ; Bone Screws/adverse effects ; Cervical Vertebrae/radiography/*surgery ; Diskectomy ; Female ; Follow-Up Studies ; Humans ; Ketones ; Lordosis/pathology ; Male ; Radiculopathy/surgery ; Severity of Illness Index ; Spinal Cord Diseases/surgery ; Spinal Diseases/*surgery ; Spinal Fusion/adverse effects/*methods ; Treatment Outcome

To test the hypothesis that exogenous purified angiotensin II (ANG) might cause apoptosis of alveolar epithelial cells (AECs) and acute lung injury, male Wistar rats were intratracheally instilled with purified ANG (10 mumol/L), ANG plus the caspase inhibitor ZVAD-fmk (60 mumol/L), ANG plus the ANG receptor AT1 antagonist losartan (LOS, 100 mumol/L) or sterile phosphate-buffered saline (PBS) vehicle alone. Six or 20 h later, the lungs were lavaged in situ for determination of bronchoalveolar lavage (BAL) fluid content of hemoglobin (Hb) and fluorescent (BODIPY)-albumin, a bolus of which was injected intravenously 15 min prior to BAL. Terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) revealed that instillation of ANG, but not PBS alone, increased labeling of fragmented DNA in bronchiolar epithelial cells and in AECs (P<0.05) at 6 h post-ANG. Increased TUNEL was abrogated by concurrent instillation of ZVAD-fmk or LOS. Significant increased numbers of caspase-positive cells were observed by anti-caspase 3 immunolabeling after instillation of ANG (P<0.01); the same doses of LOS or ZVAD-fmk that blocked TUNEL also blocked the activation of caspase 3 (P<0.01). Intratracheal instillation of ANG also remarkably increased BAL BODIPY-albumin (P< 0.01) and Hb (P<0.05), both of which were eliminated by ZVAD-fmk or LOS. These data indicate that exposure of AECs to ANG in vivo is sufficient to induce apoptosis and alveolar epithelial barrier injury mediated by ANG receptor AT1.
Amino Acid Chloromethyl Ketones ; pharmacology ; Angiotensin II ; adverse effects ; Angiotensin II Type 1 Receptor Blockers ; pharmacology ; Animals ; Apoptosis ; Caspase 3 ; metabolism ; Caspase Inhibitors ; pharmacology ; Epithelial Cells ; pathology ; Losartan ; pharmacology ; Lung Injury ; chemically induced ; pathology ; Male ; Rats ; Rats, Wistar ; Receptor, Angiotensin, Type 1 ; metabolism