Eigenvalue problems for fractional differential equations with mixed derivatives and generalized p-Laplacian

This paper reports the investigation of eigenvalue problems for two classes of nonlinear fractional differential equations with generalized p-Laplacian operator involving both Riemann–Liouville fractional derivatives and Caputo fractional derivatives. By means of fixed point theorem on cones, some sufficient conditions are derived for the existence, multiplicity and nonexistence of positive solutions to the boundary value problems. Finally, an example is presented to further verify the correctness of the main theoretical results and illustrate the wide range of their potential applications

Clinical Effects and Safety of Tongxieyaofang on Diarrhea Predominant Irritable Bowel Syndrome: A Meta-Analysis of Randomized Trails

Background. Tongxieyaofang (TXYF), a prescription originated from traditional Chinese medicine (TCM), has been widely used on treating Diarrhea Predominant Irritable Bowel Syndrome (IBS-D). The purpose of this meta-analysis was to investigate whether TXYF was effective and safe for IBS-D. Methods. We searched seven electronic databases including CENTRAL, MEDLINE, PubMed, CNKI, VIP, CBM, and Wanfang Data up to 26 July 2017. Randomized controlled trails (RCTs) were eligible, regardless of blinding. Risk of bias of included trials was evaluated according to the Cochrane Handbook. Results. The total number of participants analyzed in the meta-analysis was 3062, of which 1556 received TXYF, while 1506 received ordinary treatment. The primary outcome was clinical effective rate. Compared with conventional medication which included probiotics, pinaverium bromide, trimebutine, and Oryzanol, TXYF significantly improved the clinical effective rate (n=37, OR: 4.61; 95% CI: 3.67–5.78; P < 0.00001) and decreased the adverse events (n=10, OR: 0.26; 95% CI: 0.08–0.86; P = 0.03). There was not significant association with the score of abdominal pain, defecating frequency, fecal property, and total symptom. Conclusions. We suggested a moderate recommendation for TXYF on IBS-D, due to the fact that the risk of bias of the finally included trails was not high. Considering that all identified studies were not of high qualities and large samples, further rigorously designed and large scale RCTs were necessary to improve the applicability of our study results

Comparative efficacy of vasoactive medications in patients with septic shock: a network meta-analysis of randomized controlled trials

Abstract Background Catecholamines, especially norepinephrine, are the most frequently used vasopressors for treating patients with septic shock. During the recent decades, terlipressin, vasopressin V1A agonist, and even Ca2+ sensitizer were increasingly used by physicians. The aim of this study is to compare the efficacy of such different kinds of vasoactive medications on mortality among patients with septic shock. Methods Relevant randomized controlled trials were identified by searching PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials updated to February 22, 2018. A network meta-analysis was performed to evaluate the effect of different types of vasoactive medications. The primary outcome was 28-day mortality. Intensive care unit (ICU) mortality, hospital and ICU length of stay (LOS), and adverse events were also assessed. Results A total of 43 trials with 5767 patients assessing 17 treatment modalities were included. Treatments ranking based on surface under the cumulative ranking curve values from largest to smallest were NE/DB 85.9%, TP 75.1%, NE/EP 74.6%, PI 74.1%, EP 72.5%, VP 66.1%, NE 59.8%, PE 53.0%, DA 42.1%, DX 38.2%, SP 27.0%, PA 24.3%, EX 22.8%, LE 21.5%, and DB 13.3% for 28-day mortality. Treatments ranking for ICU mortality were TP/NE 86.4%, TP 80.3%, TP/DB/NE 65.7%, VP/NE 62.8%, NE 57.4%, VP 56.5%, PE 48.4%, DA 33.0%, PA 27.5%, LE 22.1%, and DB 9.9%. The incidence of myocardial infarction was reported with NE/EP 3.33% (n = 1 of 30), followed by EP 3.11% (n = 5 of 161), and then VP 3.10% (n = 19 of 613), NE 3.03% (n = 43 of 1417), DA 2.21% (n = 19 of 858), NE/DB 2.01% (n = 4 of 199), LE 1.16% (n = 3 of 258), and PA 0.39% (n = 1 of 257). The incidence of arrhythmia was reported with DA 26.01% (n = 258 of 992), followed by EP 22.98% (n = 37 of 161), and then NE/DB 20.60% (n = 41 of 199), NE/EP 20.0% (n = 6 of 30), NE 8.33% (n = 127 of 1525), LE 5.81% (n = 15 of 258), PA 2.33% (n = 6 of 257), and VP 1.67% (n = 10 of 600). Conclusions The use of norepinephrine plus dobutamine was associated with lower 28-day mortality for septic shock, especially among patients with lower cardiac output

MicroRNA-137 Contributes to Dampened Tumorigenesis in Human Gastric Cancer by Targeting AKT2

<div><p>MiRNAs play important roles in tumorigenesis. This study focused on exploring the effects and regulation mechanism of miRNA-137 on the biological behaviors of gastric cancer. Total RNA was extracted from tissues of 100 patients with gastric cancer and from four gastric cancer cell lines. Expression of miR-137 was detected by real-time PCR from 100 patients. The effects of miR-137 overexpression on gastric cancer cells’ proliferation, apoptosis, migration and invasion ability were investigated in vitro and in vivo. The target gene of miR-137 was predicted by Targetscan on line software, screened by dual luciferase reporter gene assay and demonstrated by western blot. As a result, the expression of miR-137 was significant reduced in gastric cancer cell line HGC-27, HGC-803, SGC-7901 and MKN-45 as well as in gastric cancer tissues compared with GES-1 cell or matched adjacent non-neoplastic tissues (<i>p</i><0.001). The re-introduction of miR-137 into gastric cancer cells was able to inhibit cell proliferation, migration and invasion. The in vivo experiments demonstrated that the miR-137 overexpression can reduce the gastric cancer cell proliferation and metastasis. Bioinformatic and western blot analysis indicated that the miR-137 acted as tumor suppressor roles on gastric cancer cells through targeting AKT2 and further affecting the Bad and GSK-3β. In conclusion, the miR-137 which is frequently down-regulated in gastric cancer is potentially involved in gastric cancer tumorigenesis and metastasis by regulating AKT2 related signal pathways.</p></div

Genomic Analysis Reveals Specific Patterns of Homozygosity and Heterozygosity in Inbred Pigs

The inbred strain of miniature pig is an ideal model for biomedical research due to its high level of homozygosity. In this study, we investigated genetic diversity, relatedness, homozygosity, and heterozygosity using the Porcine SNP60K BeadChip in both inbred and non-inbred Wuzhishan pigs (WZSPs). Our results from multidimensional scaling, admixture, and phylogenetic analyses indicated that the inbred WZSP, with its unique genetic properties, can be utilized as a novel genetic resource for pig genome studies. Inbreeding depression and run of homozygosity (ROH) analyses revealed an average of 61 and 12 ROH regions in the inbred and non-inbred genomes of WZSPs, respectively. By investigating ROH number, length, and distribution across generations, we further briefly studied the impacts of recombination and demography on ROH in these WZSPs. Finally, we explored the SNPs with higher heterozygosity across generations and their potential functional implications in the inbred WZSP. We detected 56 SNPs showing constant heterozygosity with He = 1 across six generations in inbred pigs, while only one was found in the non-inbred population. Among these SNPs, we observed nine SNPs located in swine RefSeq genes, which were found to be involved in signaling and immune processes. Together, our findings indicate that the inbred-specific pattern of homozygosity and heterozygosity in inbred pigs can offer valuable insights for elucidating the mechanisms of inbreeding in farm animals

miR-137 active cell apoptosis and negatively regulate cell invasion by targeting AKT2.

<p><b>A.</b> AKT2 protein level was assessed in GC cells treated by overexpression of miR-137 and/ or AKT2. <b>B.</b> AKT2 restoration leads to a suppression of apoptosis in GC cells while miR-137 promotes apoptosis. <b>C.</b> AKT2 restoration actives the apoptosis and invasion of GC cells while miR-137 showed opposite effects. Representative images are shown. The normalized ratio of invasive cells is shown in the bottom panels. In Fig 5, “miR-137” represents the cells transfected by miR-137 and pcDNA 3.1 empty vector. “AKT2_oe” represents the cells transfected by AKT2 overexpression vector. “miR-137 +AKT2_oe” represents the cells co-transfected by miR-137 and AKT2 overexpression vector. “Scr” represents the cells transfected with mimic negative control and pcDNA 3.1 empty vector.</p

Overexpression of miR-137 inhibits gastric cancer cell migration and invasion.

<p><b>A.</b> SGC-7901 and HGC-27 cells were not transfected or transfected with miR-137 mimics or scramble for 24 hours, and wounds were made. The relative ratio of wound closure per field is shown. As a result, cells transfected with miR-137 showed a significantly higher migrate speed compared to the control. <b>B.</b> HGC-27 and SGC-7901 cells were not transfected or transfected with miR-137 mimics or scramble for 24 hours, and transwell invasion assay was performed. The relative ratio of invasive cells per field is shown. Magnification for identification of migration is ×400 and invasion is ×40. This result demonstrated that the migration ability of lung cancer cells can be inhibited by miR-137 overexpression. <b>C.</b> Bioluminescentimaging (left) and the number of lung metastasis per mice (middle) showed that the miR-137 can suppress metastasis in vivo. The HE staining showed that the metastasis in mice lung (right).</p

MiR-137 expression in gastric cancer cells and clinical samples.

<p><b>A.</b> MiR-137 expression ingastric cancer cell lines (HGC-27, SGC-7901, SGC-7901 and MKN-45) and gastric epithelial cell (GES-1). <b>B.</b> Four patients diagnosed as gastric cancer by H&E staining (original magnification, x100). <b>C/D.</b> MiR-137 expression in 100 clinical patients. <b>E.</b> Expression levelsof miR-137 in I–II stages (n = 38) versusIII–IV stages (n = 62) of the gastric cancer patients.</p

Overexpression of miR-137 inhibits gastric cancer cell proliferation.

<p><b>A.</b> Real-time PCR was performed to detect the miR-137 expression in HGC-27 and SGC-7901 cells treated with miR-137 mimic or scramble mimic. <b>B.</b> Growth of HGC-27 and SGC-7901 cells was shown after transfection with miR-137 mimic or scramble mimic or no transfection. The growth index was assessed at 0, 1, 2, 3 and 4 days. The bars represent the mean ± SD of three independent experiments (*** means <i>P</i>< 0.001). <b>C.</b> HGC-27and SGC-7901 cells were stained with PE Annexin V and 7-AAD 72 h after treatment with miR-137mimics or scramble. Early apoptotic cells are shown in the right quadrant. <b>D.</b> Representative figure of in vivo experiments. The tumor in miR-137 overexpression group is much smaller than the scramble. <b>E.</b> HE staining of mice tumor. <b>F/G.</b> Tumor volume and weight were calculated and all data are shown as mean ± SD. These results showed that both the tumor volume and weight was significantly reduced by miR-137 overexpression. These result verified that the miR-137 overexpression can suppress tumor growth in vivo (*: <i>p</i><0.05;**: <i>p</i><0.01; ***:<i>p</i><0.001).</p