MiR-125b and SATB1-AS1 might be shear stress-mediated therapeutic targets.

The aim of the study was to explore the potential molecular mechanism associated with shear stress on abdominal aortic aneurysm (AAA) progression. This study performed RNA sequencing on AAA patients (SQ), AAA patients after endovascular aneurysm repair (EVAR, SH), and normal controls (NC). Furthermore, we identified the differentially expressed microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNA (cirRNAs) and constructed competing endogenous RNA (ceRNA) networks. Finally, 164 differentially expressed miRNAs, 179 co-differentially expressed lncRNAs, and 440 co-differentially expressed circRNAs among the three groups were obtained. The differentially expressed miRNAs mainly enriched in 325 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Target genes associated with co-differentially expressed genes among the group of SH, SQ, and NC mainly enriched in 66 KEGG pathways. LncRNA-miRNA-mRNA interactions, including 15 lncRNAs, 63 miRNAs and 57 mRNAs, was constructed. CircRNA-miRNA-mRNA ceRNA network included 79 circRNAs, 21 miRNAs, and 49 mRNAs. Among them, KLRC2 and CSTF1, targeted by miR-125b, participated in cell-mediated immunity regulation. MiR-320-related circRNAs and SATB1-AS1 serving as the sponge of miRNAs, such as has-circ-0129245, has-circ-0138746, and has-circ-0139786, were hub genes in ceRNA network. In conclusion, AAA patients might be benefit from EVAR based on various pathways and some molecules, such as miR-125b and SATB1-AS1, related with shear stress.

MiR-137 regulates low-intensity shear stress-induced human aortic endothelial cell apoptosis via JNK/AP-1 signaling.

The objective of this study is to evaluate the role of miR-137 in low-intensity shear stress-induced endoplasmic reticulum (ER) stress and cell apoptosis in human aortic endothelial cells (HAECs). HAECs were transfected with miR-137 mimic, miR-137 inhibitor, or the corresponding negative control and then exposed to pulsatile shear stress in a parallel-plate flow chamber at 1, 2, 5, 10, and 15 dyn/cm2 for 3 h. Real-time polymerase chain reaction was used to detect mRNA expression of miR-137 and SDS22. A dual-luciferase reporter assay was employed to verify the direct interaction between miR-137 and SDS22. The internal morphology of cells and cell apoptosis was assessed by TUNEL staining observed under a transmission electron microscope. Meanwhile, the protein expression of oxidative stress-related, apoptosis-related, and activated c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling-related genes were analyzed by western blotting. Low strength shear stress (0-5 dyn/cm2) caused a negative change of HAEC surface and internal morphology in an intensity-dependent manner, and these changes were gradually weakened when shear stress was increased more than 5 dyn/cm2. Furthermore, low-intensity shear stress promoted oxidative stress response, accelerated cell apoptosis, and upregulated miR-137 expression and JNK/AP-1 signaling in HAECs. MiR-137 directly targets SDS22. Knockdown of miR-137 noticeably reduced activation of JNK/AP-1 signaling, oxidative stress response, and cell apoptosis induced by shear stress. MiR-137 regulated low-intensity shear stress-induced human aortic endothelial cell ER stress and cell apoptosis via JNK/AP-1 signaling.

A Nomogram for Predicting Lymph Nodal Metastases in Patients with Appendiceal Cancers: An Analysis of SEER Database.

BACKGROUNDS: Appendiceal cancers are usually diagnosed after appendectomy accidentally. The need for subsequent right hemicolectomy in these patients was determined by the potential risk of regional lymph node (LN) metastasis. Establishing a nomogram to forecast the potential risk of lymph node metastasis of appendiceal cancer could help in the next step of treatment. METHODS: Patients with appendiceal cancer undergoing surgery was queried in the American cancer database of Surveillance, Epidemiology and End Results database from 2004 to 2016. A nomogram was established based on Logistic regression model. RESULTS: Finally, 3,075 patients were diagnosed with appendectomy cancer from 2004 to 2016. Among them, there were 2028 (65.9%) cases with negative lymph nodes, 1047 (34.1%) cases with positive lymph nodes. Risk factors associated with lymph node metastasis include age, histological type, tissue grade, T stage, distant metastasis, and tumor size. We drew the ROC curves of the training group（0.754, P < 0.001） and the validation group （0.775, P < 0.001） respectively. C-index values of predictions were 0.772 (95%CI, 0.750-0.793) and 0.776 (95%CI, 0.746-0.807), and Brier score were 0.178 and 0.172 in training and validation group respectively. All of them showed excellent performance of the nomogram in our study. CONCLUSION: A new nomogram was created to assess the potential risk of LN metastasis in patients of appendiceal cancer by utilizing age, tumor histology, tumor pathologic grade, tumor size, T-stage, and M-stage. The nomogram could provide a strong reference for the right hemicolectomy and facilitate clinic decision.

The Main Bottleneck for Non-Metastatic Pancreatic Adenocarcinoma in Past Decades: A Population-Based Analysis.

BACKGROUND Despite recent advancements in surgical techniques, chemotherapy, and radiotherapy, the 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) remains an unsatisfactory ~8%. MATERIAL AND METHODS Data were extracted to identify patients with non-metastatic pancreatic adenocarcinoma diagnosed in the periods 1988-1996 and 2010-2014 in the Surveillance, Epidemiology, and End Results (SEER) database. The statistical analyses were performed with the log-rank test, Pearson's chi-square test, propensity score matching, and Cox regression model. RESULTS The hazard ratio (HR) of surgery was reduced from 0.454 to 0.302 in Cox regression modeling, and there was no overlapping about the 95% confidence intervals (CI) of surgery between the 2 periods. The HR values of radiotherapy, which were new prognostic factor for resectable PDAC in 2010-2014, were reduced in both the resectable and unresectable groups. The upgraded chemotherapy regimen reduced the HR values from 0.738 to 0.689 in all PADC patients, and from 0.656 to 0.588 in unresectable PDAC. The log-rank test results showed that advances in surgery significantly improved the median survival from 13 months to 32 months. Radiotherapeutic and chemotherapeutic advancements extended median survival by 12 months and 11 months, respectively, in resectable PDAC. The median survivals were extended by 3 months for both of radiotherapy and chemotherapy in unresectable PDAC. CONCLUSIONS The development of chemotherapy and radiotherapy has been slow, especially for unresectable PDAC. Although advances in surgery contributed significantly to improved survival for resectable PDAC, lack of early diagnostic tools, which lead to low resection rates, remain a barrier for all PDAC patients.

Effect of neoadjuvant radiotherapy on survival of non-metastatic pancreatic ductal adenocarcinoma: a SEER database analysis.

BACKGROUND: Neoadjuvant radiotherapy has been shown to improve marginal negative resection and local control of Pancreatic Ductal Adenocarcinoma (PDAC). However, whether it improves overall survival (OS) in patients with non-metastatic PDAC remains controversial. Therefore, the purpose of this study was to analyze the benefits of only surgery, neoadjuvant radiotherapy, adjuvant radiotherapy, and surgery plus chemotherapy for OS in patients with non-metastatic PDAC. METHODS: PDAC diagnosed by surgical histopathology in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016 was selected. Kaplan-Meier analysis was used to compare the prognosis of patients with different treatments. Cox proportional risk model was used to analyze independent predictors of OS. Propensity score matching (PSM) was used to analyze the tumor prognosis of different treatment methods. RESULTS: Before PSM analysis, the OS of surgery plus chemotherapy (HRs = 0.896, 95%CIs, 0.827-0.970; P = 0.007) were significantly better than the other three treatments for stage T1-3N0M0 PDAC patients. For stage T1-3N + M0 patients, adjuvant radiotherapy (HRs = 0.613, 95% CIs, 0.579-0.649; P < 0.001) had significantly better OS than surgery plus chemotherapy and neoadjuvant radiotherapy. For stage T4N0M0 patients, neoadjuvant radiotherapy (HRs = 0.482, 95% CIs, 0.347-0.670; P < 0.001) had significantly better OS than surgery plus chemotherapy and adjuvant radiotherapy. For stage T4N + M0 patients, neoadjuvant radiotherapy (HRs = 0.338, 95% CIs, 0.215-0.532; P < 0.001) had significantly longer OS than adjuvant radiotherapy and surgery plus chemotherapy. Even after PSM, Chemotherapy plus surgery was still the best treatment for T1-3N0M0 patients. Postoperative adjuvant radiotherapy had the best prognosis among T1-3N + M0 patients, and neoadjuvant radiotherapy was the best treatment for T4 patients. CONCLUSIONS: For patients with non-metastatic PDAC, neoadjuvant radiotherapy, adjuvant radiotherapy and surgery plus chemotherapy were superior to only surgery in OS. For patients with stage T4 non-metastatic PDAC, neoadjuvant radiotherapy had the potential to be strongly recommended over adjuvant radiotherapy and surgery plus chemotherapy. However, neoadjuvant radiotherapy failed to benefit the survival of T1-3N0M0 stage patients, and surgery plus chemotherapy was preferred. For T1-3N + M0, neoadjuvant radiotherapy had no obvious advantage over adjuvant radiotherapy or surgery plus chemotherapy in OS, and adjuvant radiotherapy was more recommended.

Laminar shear stress alters endothelial KCa2.3 expression in H9c2 cells partially via regulating the PI3K/Akt/p300 axis.

In cardiac tissues, myoblast atrial myocytes continue to be exposed to mechanical forces including shear stress. However, little is known about the effects of shear stress on atrial myocytes, particularly on ion channel function, in association with disease. The present study demonstrated that the Ca2+­activated K+ channel (KCa)2.3 serves a vital role in regulating arterial tone. As increased intracellular Ca2+ levels and activation of histone acetyltransferase p300 (p300) are early responses to laminar shear stress (LSS) that result in the transcriptional activation of genes, the role of p300 and the phosphoinositide3­kinase (PI3K)/protein kinase B (Akt) pathway, an intracellular pathway that promotes the growth and proliferation rather than the differentiation of adult cells, in the LSS­dependent regulation of KCa2.3 in cardiac myoblasts was examined. In cultured H9c2 cells, exposure to LSS (15 dyn/cm2) for 12 h markedly increased KCa2.3 mRNA expression. Inhibiting PI3K attenuated the LSS­induced increases in the expression and channel activity of KCa2.3, and decreased the phosphorylation levels of p300. The upregulation of these channels was abolished by the inhibition of Akt through decreasing p300 phosphorylation. ChIP assays indicated that p300 was recruited to the promoter region of the KCa2.3 gene. Therefore, the PI3K/Akt/p300 axis serves a crucial role in the LSS­dependent induction of KCa2.3 expression, by regulating cardiac myoblast function and adaptation to hemodynamic changes. The key novel insights gained from the present study are: i) KCa2.3 was upregulated in patients with atrial fibrillation (AF) and in patients with AF combined with mitral value disease; ii) LSS induced a profound upregulation of KCa2.3 mRNA and protein expression in H9c2 cells; iii) PI3K activation was associated with LSS­induced upregulation of the KCa2.3 channel; iv) PI3K activation was mediated by PI3K/Akt­dependent Akt activation; and v) LSS induction of KCa2.3 involved the binding of p300 to transcription factors in the promoter region of the KCa2.3 gene.

[Comparison of effects of acupuncture-assisted anesthesia with different acupoint combination in gynecologic laparoscopy operation].

OBJECTIVE: To explore the best acupoint combination of acupuncture-assisted anesthesia in gynecologic laparoscopy operation. METHODS: Ninety patients, with American Society of Anesthesiologists (ASA) physical status I - II, and scheduled for elective gynecologic laparoscopy operation, were randomly divided into 3 groups, 30 cases in each group. Group I received only general anesthesia, group II and group III received general anesthesia after Han's acupoint nerve stimulator (HANS) administered for 30 min, bilateral Zusanli (ST 36) and Sanyinjiao (SP 6) were selected for group II, and bilateral Hegu (LI 4) and Taichong (LR 3) were selected for group III. During operation, the concentration of Seveflurine was adjusted to maintain NTS at D1-D2. The change of ETsev value was recorded, the heart rate (HR) and blood pressure (BP) were observed, and the time from the end of operation to extubation, awake time were recorded adverse events such as restlessness, shivering, postoperative pain, nausea and vomiting, cases of respiratory depression, the analepsia quality, the time of first anus exhaust, the awaking of patient in operation and satisfactory of patients after surgery were recorded so as to evaluate the effect of acupuncture anesthesia. RESULTS: Compared with group I, the ETsev in group II was decreased 35% (P < 0.05), group ifi was decreased 25% (P < 0.05), with a significant difference between group II and group III (P < 0.05). BP and HR had more stability in group II and group III, the best in group II. As for the time from the end of operation to extubation and the time from the end of operation to open the eye on command, group I was the longest (all P < 0.05), group III was longer, group II was the shortest. The score of restlessness, postoperative pain, vomiting and in analepsia were the highest in group I (all P < 0.05), higher in group III and the lowest in group II. Consciousness score was lowest in group I (P < 0.05). As for the satisfactory of patient after operation, it was higher in group II and group IIII (both P < 0.05 ) than group I. The time of first anus exhaust in group II and group III were significantly shorter than that in group I (both P < 0.05). CONCLUSION: Han's acupoint nerve stimulator has a certain adjuvant action for general anesthesia and analgesia and acupuncture point combination with both Zusanli (ST 36)and Sanyinjiao (SP 6) have the best effect in gynecologic laparoscopy operation. It can decrease the dosage of anaesthetic, has a stable effect on HR and BP during the surgery and has a better quality of analepsia.