Pseudolaric acid B induces apoptosis associated with the mitochondrial and PI3K/AKT/mTOR pathways in triple­negative breast cancer.

Pseudolaric acid B (PAB), a diterpene acid isolated from the root bark of Pseudolarix kaempferi, has been shown to exert strong antitumor properties. The aim of the present study was to investigate the mechanisms underlying the proposed antitumor properties of PAB in the triple­negative breast cancer cells, MDA­MB­231. The cell processes evaluated included cell proliferation by Cell Counting Kit­8 assay, colony formation and EdU assay, apoptosis by Annexin V­FITC/PI apoptosis assay, cell migration by Transwell migration assay and invasion by Transwell invasion assay. PAB significantly inhibited the proliferation of MDA­MB­231 cells through a mechanism that was considered to be associated with cell cycle arrest at the G2/M phase. There was decreased protein expression levels of CDK1 and cyclin B1 and increased protein expression levels of p53 and p21. However, there were no well­defined inhibitory effects on the normal breast cell line MCF10A. PAB also triggered apoptosis in a concentration­dependent manner through the mitochondrial apoptosis pathway. It caused collapse of mitochondrial membrane potential, accumulation of reactive oxygen species and release of cytochrome c, as well as upregulation of cleaved caspase­3, cleaved caspase­9, cleaved PARP and Bax, and downregulation of Bcl­2 and Bcl­xl. The migration and invasion ability of MDA­MB­231 cells were inhibited by decreasing the expression levels of the epithelial­mesenchymal transition­related markers N­cadherin and vimentin and increasing the expression of E­cadherin. Moreover, the expression levels of PI3K (p110ß), phosphorylated (p)­AKT (ser473) and p­mTOR (ser2448) were downregulated and LY294002, a PI3K inhibitor, could interact additively with PAB to induce apoptosis of MDA­MB­231 cells. Overall, the present results demonstrated that PAB induced apoptosis via mitochondrial apoptosis and the PI3K/AKT/mTOR pathway in triple­negative breast cancer. It also inhibited cellular proliferation, migration and invasion, suggesting that PAB may be a useful phytomedicine for the treatment of triple­negative breast cancer.

Modified Xiaochaihu Decoction for gastroesophageal reflux disease: A randomized double-simulation controlled trial.

BACKGROUND: Gastroesophageal reflux disease (GERD) has a high prevalence worldwide, and its incidence is increasing annually. Modified Xiaochaihu Decoction (MXD) could relieve the symptoms of GERD, but the effects of MXD on GERD manifestations and relapse prevention need to be further explained. Therefore, we performed a prospective, double-blind, and double-simulation study. AIM: To verify the efficacy of MXD for GERD and its effect on esophageal motility. METHODS: Using randomization, double-blinding, and a simulation design, 288 participants with GERD were randomized to the treatment group and control group and received herbs (MXD) plus omeprazole simulation and omeprazole plus herbs simulation, respectively, for 4 wk. The GERD-Q scale score and esophageal manometry were measured at baseline, after treatment, and at 1 mo and 3 mo follow-up visits when medication was complete to evaluate recurrence indicators. RESULTS: The GERD-Q scale score in both groups decreased significantly compared to those before treatment (P < 0.01). However, no significant difference was observed between the two groups (P > 0.05). Esophageal manometry showed that participants with lower esophageal sphincter pressure reduction and the proportion of ineffective swallowing (more than 50%) improved in both groups from baseline (P < 0.01), especially in the treatment group (P < 0.05). The percentage of small intermittent contractions, large intermittent contractions, and increased pre-phase contractions in the treatment group significantly improved compared with baseline (P < 0.05) but did not improve in the control group (P > 0.05). There was no significant difference between the groups after treatment (P > 0.05). The percentage of weak esophageal contractility (distal contractile integral < 450 mmHg·s·cm), improved in both groups (P < 0.01), but no significant difference was observed between the groups after treatment (P > 0.05). The relapse rate in the treatment group was lower than that in the control group at the 1 mo (P < 0.01) and 3 mo follow-up (P < 0.05). CONCLUSION: MXD has a similar therapeutic effect to omeprazole in mild-to-moderate GERD. The therapeutic effect may be related to increased pressure in the lower esophageal sphincter and reduced ineffective swallowing.

Post-marketing Re-evaluation of Tongxiening Granules () in Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Multi-center, Randomized, Double-Blind, Double-Dummy and Positive Control Trial.

OBJECTIVE: To evaluate the efficacy and safety of Tongxiening Granules (, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D). METHODS: A randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated. RESULTS: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05). CONCLUSION: Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415).

The impact of FLT3 mutations on treatment response and survival in Chinese de novo AML patients.

OBJECTIVE: Two distinct forms of FMS-like tyrosine kinase 3 (FLT3) mutations, internal tandem duplication (ITD) in the juxtamembrane domain and point mutation within the activation loop of the tyrosine kinase domain (TKD), have been identified in considerable number of patients with AML. This study was aimed to analyze the impacts of these mutations on clinical outcomes, and assess the efficacy of different therapeutic regimens (allo-HSCT, sorafenib, or conventional chemotherapy) for AML patients with FLT3 mutations after the standard induction therapy. MATERIALS AND METHODS: We analyzed DNA samples from 158 consecutive de novo AML patients (18-60 years, excluding APL) with FLT3 mutations between July 2010 and October 2015. RESULTS: We found that AML patients with FLT3-TKD mutations have more favorable clinical outcomes than those with FLT3-ITD mutations. We also found that allo-HSCT therapy subgroup achieved longer OS and RFS than non-allo-HSCT therapy subgroup for FLT3-ITD positive patients (p < 0.001, p = 0.071). However, compared with the clinical outcomes in non-primary refractory patients, sorafenib did not show an obvious beneficial effect for the primary refractory patients. Further study on a large scale is still recommended. CONCLUSIONS: FLT3-TKD-mutated AML patients have more favorable clinical outcomes than those with FLT3-ITD mutations. Allo-HSCT therapy subgroup achieved longer OS and RFS than non-allo-HSCT therapy subgroup for FLT3-ITD positive patients. Compared with the clinical outcomes in non-primary refractory patients, sorafenib did not show an obvious beneficial effect for the primary refractory patients.

[Clinical observation on auricular-plaster therapy combined with chiropractics for treatment of emaciation in children].

OBJECTIVE: To search for a non-medicine therapy for infant emaciation. METHODS: The observation group of 55 cases were treated with auricular point sticking combined with chiropractics. For the auricular point sticking therapy, vaccaria seeds were stuck at 9 points such as small intestine, Shenmen, spleen, endocrine, and others, and replaced once every 5 days, 10 days constituting one course. Chiropractics: knead or massage the muscles from lumbosacral area upward to Dazhui (GV 14). The control group were treated with oral administration of pepsin mixture, 10 mL after meals, thrice each day. They were treated for 5 courses. RESULTS: Of the 55 cases in the observation group, 7 were cured, 20 markedly effective, 24 effective and 4 ineffective, with a total effective rate of 92.7%, and among the 23 cases in the control group, 2 cases were cured, 7 markedly effective, 8 effective and 6 ineffective, with a total effective rate of 73.9%. CONCLUSION: Auricular point sticking combined with chiropractics is a better non-medicine therapy for emaciation in children.