The Active Fraction of Polyrhachis vicina Roger (AFPR) activates ERK to cause necroptosis in colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Polyrhachis vicina Roger (P. vicina), a traditional Chinese medicinal animal, has been used to treat rheumatoid arthritis, hepatitis, cancer, and other conditions. Due to its anti-inflammatory properties, our previous pharmacological investigations have demonstrated that it is effective against cancer, depression, and hyperuricemia. Nevertheless, the key active components and targets of P. vicina in cancers are still unexplored. AIM OF THE STUDY: The study aimed to evaluate the pharmacological treatment mechanism of the active fraction of P. vicina (AFPR) in treating colorectal cancer (CRC) and to further reveal its active ingredients and key targets. METHODS: To examine the inhibitory impact of AFPR on CRC growth, tumorigenesis assays, cck-8 assays, colony formation assays, and MMP detection were utilized. The primary components of AFPR were identified by GC-MS analysis. The network pharmacology, molecular docking, qRT-PCR, western blotting, CCK-8 assays, colony formation assay, Hoechst staining, Annexin V-FITC/PI double staining, and MMP detection were performed to pick out the active ingredients and potential key targets of AFPR. The function of Elaidic acid on necroptosis was investigated through siRNA interference and the utilization of inhibitors. Elaidic acid's effectiveness to suppress CRC growth in vivo was assessed using a tumorigenesis experiment. RESULTS: Studies confirmed that AFPR prevented CRC from growing and evoked cell death. Elaidic acid was the main bioactive ingredient in AFPR that targeted ERK. Elaidic acid greatly affected the ability of SW116 cells to form colonies, produce MMP, and undergo necroptosis. Additionally, Elaidic acid promoted necroptosis predominantly by activating ERK/RIPK1/RIPK3/MLKL. CONCLUSION: According to our findings, Elaidic acid is the main active component of AFPR, which induced necroptosis in CRC through the activation of ERK. It represents a promising alternative therapeutic option for CRC. This work provided experimental support for the therapeutic application of P. vicina Roger in the treatment of CRC.

Hypoxia-Induced miR-137 Inhibition Increased Glioblastoma Multiforme Growth and Chemoresistance Through LRP6.

PURPOSE: Glioblastoma multiforme (GBM) is one of the deadliest tumors, which is involved in numerous dysregulated microRNAs including miR-137. However, the mechanism of how miR-137 suppression associated with cancer progression and chemoresistance still remains to be elucidated. METHODS: Quantitative reverse transcriptase-PCR (qRT-PCR), DNA methylation analysis, cell proliferation assay, flow cytometric analysis, invasion assay, in situ tumor formation experiment were performed to test the expression levels and functions of miR-137 in GBM. Bioinformatics analysis, luciferase reporter assay, qRT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry assay were used to identify and verify the target of miR-137. RESULTS: We found that miR-137 was downregulated in primary and recurrent GBM compared with normal brain tissues. Overexpression of miR-137 inhibited cell invasion and enhanced cell chemosensitivity to temozolomide (TMZ) by directly targeting low-density lipoprotein receptor-related protein 6 (LRP6) in GBM. Forced expression of LRP6 cDNA without its 3'-UTR region partly restored the effects of miR-137 in vitro and in vivo. Hypoxia-induced miR-137 methylation was responsible for the miR-137 suppression, leading to the cell chemoresistance and poor prognosis of GBM. CONCLUSIONS: These findings demonstrated the detailed molecular mechanism of miR-137 in regulating GBM growth and chemoresistance in hypoxia microenvironment, suggesting the potentiality of miR-137 as a therapeutic target for GBM.

Active fraction of Polyrhachis vicina Rogers (AFPR) suppressed breast cancer growth and progression via regulating EGR1/lncRNA-NKILA/NF-κB axis.

Breast cancer (BC) is a major contributor of cancer-associated mortality in women. It is essential to find new therapeutic targets and drugs. Polyrhachis vicina Rogers is one of the Traditional Chinese Medicine (TCM). Our previous studies have shown an active fraction of Polyrhachis vicina Rogers (AFPR) has significant anti-inflammatory activity, suggesting its anti-cancer effect. Here, we aimed to explore the inhibitory effects of AFPR on BC and reveal its mechanism. The effects of AFPR on BC were examined by cell proliferation assay, wound healing assay, invasion assay and xenograft assay. Microarray sequencing, qRT-PCR, Western blot, chromatin immunoprecipitation assay and luciferase reporter assay were performed to investigate the regulation of AFPR on related genes and underlying mechanisms. As a result, AFPR suppressed BC cell growth, migration and invasion and inhibited tumor growth. LncRNA NKILA was most prominently upregulated in AFPR-treated MCF7 cells. AFPR inactivated NF-κB signaling pathway via regulating NKILA. Furthermore, AFPR regulated the expression of NKILA by inhibiting its transcript suppressor EGR1. This study firstly indicated that AFPR was a potential inhibitor of BC development via regulating EGR1/NKILA/NF-κB axis.

Associations of anxiety with discomfort and tolerance in Chinese patients undergoing esophagogastroduodenoscopy.

OBJECTIVES: To evaluate the associations of pre-endoscopy anxiety with discomfort and tolerance in patients undergoing unsedated esophagogastroduodenoscopy (EGD). METHODS: This is a hospital-based cohort study of 348 patients undergoing routine, non-advanced EGD without sedation. The primary outcomes were discomfort and tolerance. The anxiety before endoscopy was evaluated with a 10-point visual analogue scale (VAS). The associations of pre-endoscopy anxiety with the outcomes were evaluated with logistic regression adjusting for potential confounders like age, sex, and body mass index. RESULTS: Seventy patients reported severe discomfort and 56 patients reported poor tolerance after endoscopy. The risk of severe discomfort increased with pre-endoscopy anxiety and reached a platform around 7-10 points. Compared with the participants with low pre-endoscopy anxiety, those with moderate (adjusted odds ratio [OR] 2.70, 95% confidence interval [CI] 1.17 to 6.22) and high level of anxiety (adjusted OR 6.87, 95% CI 2.16 to 21.79) were associated with a gradual increase in the risk of severe discomfort (P-trend < 0.001). The association between pre-endoscopy anxiety and tolerance was linear, with an adjusted OR of 1.67(95% CI 1.33 to 2.08) for a 1-score increase in pre-endoscopy anxiety VAS. The associations were not modified by age, sex, pharyngitis, duration of endoscopy, and diameter of the endoscope. CONCLUSIONS: Pre-endoscopy anxiety was an independent predictor of severe discomfort and poor tolerance in Chinese patients undergoing unsedated EGD. Our findings suggested the importance of the management of anxiety to reduce adverse endoscopic experience and taking high level of anxiety as an indication for sedation.

Proton pump inhibitors for preventing non-steroidal anti-inflammatory drug induced gastrointestinal toxicity: a systematic review.

OBJECTIVE: Proton pump inhibitors (PPIs) are recommended for preventing gastrointestinal lesions induced by non-steroidal anti-inflammatory drugs (NSAIDs). We performed this study: (1) to evaluate the effectiveness and safety of PPIs, (2) to explore the association between effectiveness and potential influential factors, and (3) to investigate the comparative effect of different PPIs. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched to identify randomized controlled trials comparing different classes of PPIs, or comparing PPIs with placebo, H2 receptor antagonists or misoprostol in NSAIDs users. Both pairwise meta-analysis and Bayesian network meta-analysis were performed. RESULTS: Analyses were based on 12,532 participants from 31 trials. PPIs were significantly more effective than placebo in reducing ulcer complications (relative risk [RR] = 0.29; 95% confidence interval [CI], 0.20 to 0.42) and endoscopic peptic ulcers (RR = 0.27; 95% CI, 0.22 to 0.33), with no subgroup differences according to class of NSAIDs, ulcer risk, history of previous ulcer disease, Helicobacter pylori infection, or age. To prevent one ulcer complication, 10 high risk patients and 268 moderate risk patients need PPI therapy. Network meta-analysis indicated that the effectiveness of different PPIs in reducing ulcer complications and endoscopic peptic ulcers is generally similar. PPIs significantly reduced gastrointestinal adverse events and the related withdrawals compared to placebo; there is no difference in safety between different PPIs. CONCLUSIONS: PPIs are effective and safe in preventing peptic ulcers and complications in a wide spectrum of patients requiring NSAID therapy. There is no major difference in the comparative effectiveness and safety between different PPIs.

Network Meta-Analysis Comparing Relatively Selective COX-2 Inhibitors Versus Coxibs for the Prevention of NSAID-Induced Gastrointestinal Injury.

Currently 2 difference classes of cyclooxygenase (COX)-2 inhibitors, coxibs and relatively selective COX-2 inhibitors, are available for patients requiring nonsteroidal anti-inflammatory drug (NSAID) therapy; their gastroprotective effect is hardly directly compared. The aim of this study was to compare the gastroprotective effect of relatively selective COX-2 inhibitors with coxibs. MEDLINE, EMBASE, and the Cochrane Library (from their inception to March 2015) were searched for potential eligible studies. We included randomized controlled trials comparing coxibs (celecoxib, etoricoxib, parecoxib, and lumiracoxib), relatively selective COX-2 inhibitors (nabumetone, meloxicam, and etodolac), and nonselective NSAIDs with a study duration ≥ 4 weeks. Comparative effectiveness and safety data were pooled by Bayesian network meta-analysis. The primary outcomes were ulcer complications and symptomatic ulcer. Summary effect-size was calculated as risk ratio (RR), together with the 95% confidence interval (CI). This study included 36 trials with a total of 112,351 participants. Network meta-analyses indicated no significant difference between relatively selective COX-2 inhibitors and coxibs regarding ulcer complications (RR, 1.38; 95% CI, 0.47-3.27), symptomatic ulcer (RR, 1.02; 95% CI, 0.09-3.92), and endoscopic ulcer (RR, 1.18; 95% CI, 0.37-2.96). Network meta-analyses adjusting potential influential factors (age, sex, previous ulcer disease, and follow-up time), and sensitivity analyses did not reveal any major change to the main results. Network meta-analyses suggested that relatively selective COX-2 inhibitors and coxibs were associated with comparable incidences of total adverse events (AEs) (RR, 1.09; 95% CI, 0.93-1.31), gastrointestinal AEs (RR, 1.04; 95% CI, 0.87-1.25), total withdrawals (RR, 1.00; 95% CI, 0.74-1.33), and gastrointestinal AE-related withdrawals (RR, 1.02; 95% CI, 0.57-1.74). Relatively selective COX-2 inhibitors appear to be associated with similar gastroprotective effect and tolerability as coxibs. Owing to the indirectness of the comparisons, future research is required to confirm the study conclusion.

[Open high tibial osteotomy through small incision with annular external fixator for treating genu varum deformity].

OBJECTIVE: To evaluate the outcomes of open high tibial osteotomy through small incision with annular external fixator for treating genu varum deformity. METHODS: We reviewed 8 cases of open high proximal tibia osteotomy through small incision with annular external fixator for patients (10 knees) with genu varum due to high tibia varum. The patients were followed up 1, 2, 3, 6, 12, 24 and 36 months after the operations. Data about infection, healing, varus angle, knee distance and Insall-Salvati index were retrieved and analysed. RESULTS: The patients had a mean varus angle of 15. 3 degrees +/- 2. 3 degrees (range, 10 degrees - 28 degrees) before the operations. The operations were all recorded as successful following a (29. 3 +/- 3. 1) month (range, 24-36 months) post-operation follow-up, with external fixator remaining stable and no instrument failures. The bones were healed at an average of (11. 2 +/- 1. 5) weeks (range, 8-12 weeks) and there was no nonunion or delayed union. The operations reduced varus angle of the knees to - 1. 1 degrees +/- 0. 6 degrees (range, - 7 degrees - 3 degrees ), indicating a significant improvement compared to that of the preoperations. There were 2 cases of superficial pin infections. CONCLUSION: Open high tibial osteotomy through small incision with annular external fixator has good fixation stability and satisfactory clinical outcomes with little complications for treating patients with genu varum deformity.

Meta-analysis comparing total hip arthroplasty with hemiarthroplasty in the treatment of displaced femoral neck fractures in patients over 70 years old.

OBJECTIVE: Total hip arthroplasty (THA) and hemiarthroplasty (HA) are effective methods currently used to treat femoral neck fracture in elderly patients, but the two options remain controversial in patients over 70 years old. The main purpose of our study was to determine whether THA or HA is a superior treatment of femoral fractures involving a displaced neck in patients who are over 70 years of age. METHODS: A computer-based online search of Medline (1970-2011), PubMed (1977-2011), and the Cochrane Central Register of Controlled Trials (2002-2011) was conducted. Six relevant randomized controlled trials with a total of 739 patients were included for the final analysis. The analysis was performed with software RevMan 5.0. RESULTS: We found that compared with THA, HA needed shorter average time and lost less blood. While over the long-term follow-up, THA patients exhibited significantly less pain and better function and were less likely to require a revision hip surgery. Postoperative infection was equally common among HA and THA patients. CONCLUSIONS: The significant differences in outcomes suggest that THA is a valuable treatment option for active elderly hip fracture individuals. However, patients who are older, impaired or institutionalized benefit from HA.

[Reconstruction of the three-dimensional structure of senile plaques in Alzheimer disease].

Senile plaques are one of the major neuropathological features of Alzheimer's disease (AD). Aggregation of Amyloid beta-protein(A beta) in senile plaques is related to the pathogenesis of AD, so it is very important for the studies on the prevention of A beta deposition and on trying to disaggregate the senile plaques, aimed at treatment and prevention of the AD. In this report, the three-dimension structures of senile plaques are reconstructed by AVS software by using immunohistochemical method and MATLAB software. The diffuse plaques and classical plaques in hippocampus all have complicated porous structures; no core structures were present in diffuse plaques, and the deposition density of A beta in this kind of plaque diminishes from interior region to the microenvironment. The deposition density of A beta was highest in the central region of classical plaques, while was lowest in the region around central, and was intermediate in the extreme region of this kind of plaques. The method of reconstruction of three-dimension structure of senile plaques helps studying on dynamics of senile plaques, and it is also important for the studies on the pathogenesis of AD.