A case of spontaneous isolated superior mesenteric arterial dissection with coeliac axis stenosis.

Spontaneous isolated superior mesenteric arterial dissection with coeliac axis stenosis is rare but serious. We report a case of a 54-year-old male with coeliac axis stenosis who presented with acute superior mesenteric arterial dissection, which caused thrombosis of the branches. This is the first report of the full course of treatment using endovascular repair and laparoscopic surgery to deal with spontaneous isolated superior mesenteric arterial dissection combined with coeliac axis stenosis. This approach has been shown to be safe and effective for yielding short-term results.

PER1 promotes functional recovery of mice with hindlimb ischemia by inducing anti-inflammatory macrophage polarization.

Hindlimb ischemia (HLI) is an arterial occlusive disease that exposes the patients to the risk of limb gangrene and loss. Polarization of macrophages is related to HLI-induced inflammation. Period circadian regulator 1 (PER1) is a core component of the circadian clock. We first showed, based upon bioinformatics analysis of microarray data, that PER1 expression was reduced in monocytes from patients with critical limb ischemia. The proximal femoral artery in the left hindlimb of male mice was ligated and then the femoral artery and its collateral branches were removed to establish the HLI mouse model. After modeling, a single intramuscular injection of 1 × 109 pfu Ad-PER1 was performed at the adductor and gastrocnemius muscles. The gastrocnemius muscle tissues were collected at day 0, 3, 7, 14, 21 post-HLI. There was obvious pathological necrosis, accompanied with reduced expression of PER1 in the muscle tissues of HLI mice. Expression of CD68 and CD31 seemed to be corresponded to PER1 in gastrocnemius muscle, implying the potential of PER1 in regulating macrophage-related inflammation and angiogenesis. PER1 overexpression diminished myocyte damage, promoted blood flow restoration and improved behavioral scores of HLI mice. Immunostaining of CD31 and α-SMA revealed that PER1 upregulation reversed HLI-induced decreases in capillary and arteriole density. In vitro, RAW264.7 cells were cultured in hypoxia (1% O2) for 24 h. The percentage of pro-inflammatory CD86+ macrophages (M1 type) was decreased and that of anti-inflammatory CD206+ macrophages (M2 type) was increased when PER1 was overexpressed. Moreover, the expression levels of TNF-α, IL-6 and M1-type marker iNOS were decreased, and levels of IL-10 and M2-type marker Arg-1 were increased by PER1 in gastrocnemius muscle of HLI mice and hypoxia-treated RAW264.7 cells. PER1 might reduce M1 macrophage polarization and promote M2 macrophage polarization, and thus exert anti-inflammatory and pro-angiogenic actions. Our findings suggest that PER1 overexpression promotes functional recovery of mice with HLI through regulating macrophage polarization.

MiR-361-5p exerts tumor-suppressing functions in gastric carcinoma by targeting syndecan-binding protein.

MiR-361-5p, a tumor-related microRNA, has been reported to be implicated in the tumorigenesis and progression of diverse types of human malignancies; however, its role in gastric carcinoma remains unclear. This study aimed to explore the biological role of miR-361-5p in gastric carcinoma and clarify the potential mechanisms involved. In the present study, miR-361-5p was found to be significantly downregulated in both gastric carcinoma tissues and cell lines. Functional studies demonstrated that enhanced expression of miR-361-5p suppressed gastric carcinoma cell proliferation in vitro, inhibited tumor growth in vivo, and induced gastric carcinoma cell apoptosis. Moreover, the tumor-suppressing effects of miR-361-5p in gastric carcinoma were abrogated by the miR-361-5p inhibitor treatment. Notably, syndecan-binding protein was downregulated by miR-361-5p via direct binding to its 3' untranslated region in gastric carcinoma cells. Furthermore, syndecan-binding protein expression was discovered to be markedly upregulated and inversely correlated with miR-361-5p expression in gastric carcinoma tissues. Mechanistic studies revealed that restoring the expression of syndecan-binding protein alleviated miR-361-5p-induced inhibitory effects on proliferation of gastric carcinoma cells. Taken together, these findings suggest that miR-361-5p functions as a tumor suppressor in gastric carcinoma by directly targeting syndecan-binding protein and that miR-361-5p might be a novel therapeutic target for gastric carcinoma.

[Application of intraoperative ultrasound in laparoscopic lymphadenectomy of gastric cancer].

OBJECTIVE: To explore the application value of intraoperative ultrasound (IU) in laparoscopic lymphadenectomy of gastric cancer. METHODS: Patients with gastric cancer undergoing laparoscopic radical D2 gastrectomy at General Surgery of the Second Affiliated Hospital of Anhui Medical University between August 2016 and May 2018 were prospectively enrolled and were randomly divided into IU group (n=78) and conventional group (n=91). The conventional group underwent laparoscopy only. In IU group, the laparoscopy examination was followed with intraoperative ultrasound by ultrasound specialist. The lesser curvature, peripheral gastric organs and gastric lymph nodes were scanned. Lymph nodes were considered positive if maximum diameter was greater than 10 mm or internal hyperechoic features and normal oval shape were lost. The postoperative pathological results were used as the gold standard to analyze the sensitivity of positive lymph nodes by IU detection [true positive lymph nodes/(true positive lymph node+false negative lymph nodes)×100%], specificity [true negative lymph nodes/(true negative lymph nodes+false positive lymph nodes)×100%] and the accuracy rate[(true positive lymph nodes+ true negative lymph nodes/total lymph nodes)×100%]. A consistency check between N staging diagnosed by IU and by postoperative pathology was performed with Kappa test(Kappa>0.75 indicating good consistency). Number of dissected lymph node, number of positive lymph node detected by pathology and the operation time were compared between the IU group and the conventional group. RESULTS: Among 169 gastric cancer patients, 95 were males and 74 were females with age of (63±8) years. Among 1 794 lymph nodes detected by IU from 78 patients in IU group, predicted positive lymph nodes were 832 and 740 positive nodes were confirmed by postoperative pathology. True positive lymph nodes were 679 and true negative lymph nodes were 901 by IU, and a total of 1 580 lymph nodes were accurately diagnosed by IU. The sensitivity and specificity of IU for N staging of gastric cancer were 91.8%(679/740) and 85.5%(901/1 054), respectively. Overall accuracy was 88.1%(1 580/1 794), which was in good accordance with postoperative N staging(Kappa=0.758). There was no significant difference in number of lymph node detected between the IU group and conventional group during laparoscopic gastric cancer surgery(23.0±6.9 vs. 22.0±7.7, t=0.880, P=0.380). However, the numbers of lymph nodes in the third station (No.10, No.11, No.12) in the IU group were significantly higher than those in the conventional group [No.10: median 1 (0-1) vs. 0 (0-1), Z=-6.307, P<0.001; No.11: median 1(0-2) vs. 0(0-1), Z=-5.895, P<0.001; No.12: median 1 (0-1) vs. 0 (0-1), Z=-6.693, P<0.001]. There was no significant difference in the number of positive lymph node between IU group and the conventional group(P>0.05), but the number of positive lymph nodes dissected in stage III patients of IU group was significantly higher than that in stage III patients of conventional group (14.6±4.8 vs. 14.0±3.6, t=2.531, P=0.011). The operative time of IU group was(272.0±12.0) minutes, which was significantly longer than (249.0±7.0) minutes of conventional group (t=14.638, P<0.001). However, with the increase of patients undergoing IU, the operation time of IU showed a downward trend. The average operation time of the last 20 patients was 264 minutes, and the average IU time was 15 minutes. CONCLUSIONS: Intraoperative ultrasound is more accurate N-staging of gastric cancer. Although increasing operation time, it is helpful for lymph node dissection in laparoscopic gastric cancer surgery, especially by providing good support for laparoscopic No.10, No.11 and No.12 lymph nodes dissection.

miR-133b acts as a tumor suppressor and negatively regulates ATP citrate lyase via PPARγ in gastric cancer.

MicroRNAs (miRNAs/miRs) are a class of small noncoding RNAs that negatively regulate protein expression by binding to protein-coding mRNAs and suppressing translation. Accumulating evidence suggests that miRNAs are involved in the development and progression of cancer by regulating cancer metabolism. Meanwhile, the cytosolic enzyme ATP citrate lyase (ACLY) is a promising target in the prevention and treatment of cancer. In the present study we revealed by western blot analysis and reverse transcription­quantitative PCR that miR-133b was downregulated in human gastric cancer (GC) tissues and cell lines, while ACLY was upregulated. The overexpression of miR-133b could decrease the proliferation and invasion of MKN-74 cells by inhibiting the expression and activation of ACLY. Furthermore, the nuclear distribution of peroxisome proliferator-activated receptor-γ (PPARγ) in GC tissues and cell lines was markedly decreased, and overexpression of miR-133b could increase the levels of nuclear PPARγ in MKN-74 cells. Additionally, miR-133b decreased the transcriptional activity of ACLY in a PPARγ-dependent manner, as determined by a dual-luciferase reporter assay. These results indicate that miR-133b targets ACLY and inhibits GC cell proliferation by regulating the expression of PPARγ, suggesting that miR-133b may serve as a tumor-suppressive target in GC therapy.

Cecropin-P17, an analog of Cecropin B, inhibits human hepatocellular carcinoma cell HepG-2 proliferation via regulation of ROS, Caspase, Bax, and Bcl-2.

Cecropin-P17 is a peptide derived from Cecropin B. In this study, we investigated the effects and relative mechanisms of Cecropin-P17 in a human liver cancer cell line (HepG-2) in vitro and in vivo. A cell viability assay, Annexin V/propidium iodide assay, western blot, flow cytometry, quantitative real-time polymerase chain reaction, and a tumor-xenograft model were applied to elucidate the mechanism exerted by Cecropin-P17 on HepG-2 cells. Cecropin-P17 significantly inhibited the proliferation of HepG-2 cells and demonstrated low cytotoxicity to normal liver cells in vitro. The apoptotic rate of HepG-2 cells was increased after Cecropin-P17 treatment together with increased production of reactive oxygen species. Moreover, Cecropin-P17 stimulated caspase-3, caspase-9, and Bax and inhibited Bcl-2 on both the transcriptional and translational levels. Finally, Cecropin-P17 significantly suppressed tumor growth in a HepG-2-bearing nude mouse model. All of these results indicated that Cecropin-P17 could be a potential agent for the treatment of liver cancer.

FOXA1 positively regulates gene expression by changing gene methylation status in human breast cancer MCF-7 cells.

OBJECTIVE: DNA methylation is an important epigenetic modification with tumor suppressor gene silencing in cancer. The mechanisms underlying DNA methylation patterns are still poorly understood. This study aims to evaluate the potential value of FOXA1 for controlling gene CpG island methylation in breast cancer. METHODS: FOXA1 was down-regulated by transfection with siRNA and up-regulated by transfection with plasmid in MCF-7 cell lines. The DNA methylation and mRNA levels were examined by qMSP and qRT-PCR. The cell proliferation and apoptosis was detected by MTT and Flow cytometry. RESULTS: Suppression of FOXA1 enhanced the methylation status of DAPK, MGMT, RASSF1A, p53, and depressed mRNA levels of these tumor suppressor genes, whereas over-expression of FOXA1 showed the opposite effects. DNMT1, DNMT3A and DNMT3B mRNA were up-regulated by siRNA knock-down of FOXA1. At the same time, FOXA1 suppression promoted cell growth and inhibited apoptosis. CONCLUSIONS: FOXA1 may be associated with methylation of the tumor suppressor genes promoter through changing DNMTs expression. FOXA1 could be a potential demethylation target for prevention and treatment of breast cancer.

Potential health risks of heavy metals in cultivated topsoil and grain, including correlations with human primary liver, lung and gastric cancer, in Anhui province, Eastern China.

Environmental exposure to heavy metals is a well-known risk factor for cancers. To evaluate potential health risks of heavy metals (Cr, Cd, Pb, As and Hg) and Se in cultivated topsoil and grains, we investigated the concentrations of Hg, As and Se using atomic fluorescence spectrometry and Cr, Cd and Pb using inductive coupled plasma emission spectrometry (ICP-MS). We also analyzed human cancer tissues for heavy metals. Potential health risks for local residents were evaluated by calculating the hazard index (HI) and the total carcinogenic risk (TCR) for soil heavy metals and the target hazard quotient (THQ) and the carcinogenic risk (CR) for grain heavy metals. A bioconcentration factor (BCF) was applied to quantify the bioaccumulation of heavy metals. Our results demonstrated that the mean concentrations of heavy metals in soil were all within the safety limits set by FAO/WHO and Chinese regulations; however, the mean concentrations of Cr and Hg in grain exceeded the safety limits. HI and TCR for soil heavy metals were all within acceptable levels, but the THQ for four grain heavy metals exceeded the target value of 1 (Cr, 2.64; Pb, 1.41; As, 1.24; Hg, 1.07; Cd, 0.39). The grain CR for Cr, Pb and As exceeded the accepted risk level of 10(-6). BCF values indicated that the bioaccumulation capacity decreased in the following sequence: Hg>Se>Cd>Cr>Pb>As. We also observed statistically significant correlations of topsoil Pb concentration with human gastric cancer and grain Hg with human liver cancer. Therefore, long-term low dose exposure of heavy metals may play a key role in tumorigenesis, and it may not be necessary to accumulate a high concentration of heavy metals in the human body for those metals to induce tumorigenesis.

[Effects of batroxobin and electric cauterization on vascular remodeling of rabbit with a removal of carotid arterial adventitia].

OBJECTIVE: To explore the topical hemostatic effects of batroxobin (BX) and electric cauterization (EC) on capillary hemorrhage of rabbit with a removal of carotid arterial adventitia. METHODS: A total of 27 New Zealand rabbits were randomly divided into control, BX and EC groups. Each group received BX (2 kU/L), EC (power = 40 W) and saline for topical hemostasis after a removal of carotid arterial adventitia and blunt dissection. The animals were euthanized by 0, 14 and 28 d post-operation. The specimens of adventitia removal section were divided into three parts for histology (hematoxylin and eosin, MASSON & transmission electron microscope), immunohistochemistry (IHC) [monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF)] and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: At Day 28 post-operation, the remodeling index, stenotic rate and collagen fiber density of BX and EC groups were (0.753 ± 0.0739) and (0.618 ± 0.0989), (0.298 ± 0.030)% and (0.363 ± 0.039)%, (15.4 ± 3.5)% and (23.4 ± 5.1)% respectively. There was statistically significant difference between two groups (P < 0.05) while no difference existed between hemocoagulase and control groups. The results of electron microscopy showed that the atrial fibroblasts of EC group increased markedly versus BX group. As demonstrated by RT-PCR and IHC, the expressions of MCP-1, TGF-ß1 and VEGF in BX group were lower than those in EC group (P < 0.05) while no difference versus the control group. CONCLUSION: As a safe and effective topical hemostatic method, BX can effectively decrease inflammation response and reduce vascular remodeling and narrowing in rabbits with a removal of carotid arterial adventitia. And its effect mimic closely natural conditions.

Hemocoagulase atrox reduces vascular modeling in rabbit carotid artery adventitia.

OBJECTIVE: This study aimed to compare the effects of hemocoagulase atrox and cauterization hemostasis on intimal hyperplasia and explore the effect of hemocoagulase atrox on vascular modeling in rabbit carotid artery adventitia. METHODS: A total of 27 rabbits were randomly divided into 3 groups (0d, 14d, 28d). They were anaesthetized using an intramuscular injection of phenobarbital sodium (1 ml/kg). The left and right common carotid arteries were exposed and capillary hemorrhaged after blunt dissection of the adventitia layers of common carotid arteries. Nine rabbits in each group were again randomly divided into 3 groups, in which animals were respectively treated with hemocoagulase (2 U/ml), cauterization (power = 40 w) and saline (as control). Groups of animals were euthanized at 0, 14 and 28 days after surgery. The samples were equally divided in the middle of the adventitia removal section to obtain equal parts for histologic, immunohistochemical and molecular biologic analysis. The vascular repair after adventitial stripping was observed by HE staining, Masson staining and transmission electron microscopy. The expression of carotid MCP-1, PCNA, TGF-ß1, α-SMA and VEGF were measured at different time points by RT-PCR and immunohistochemical staining. RESULTS: HE staining and Masson staining showed that hemocoagulase atrox had a significantly stronger effect on reducing intimal hyperplasia than the cauterization after 14 and 28 days. The results of RT-PCR showed that the expression of MCP-1, TGF-ß1, α-SMA and VEGF in hemocoagulase atrox-treated animals were lower than that of cauterization-treated animals. CONCLUSION: Our results suggested that hemocoagulase atrox as a topical hemostatic is safety and efficiently and it can accelerate adventitia restoration and decrease intimal proliferation.

[The topically hemostatic effects of batroxobin on the carotid arteries adventitia removal rabbit].

OBJECTIVE: To observe the topically hemostatic effects of batroxobin (BX) in different concentrations on the carotid arteries adventitia removal rabbit. METHODS: 18 rabbits were removed vascular adventitia by collagenase digestion and mechanical dissection, causing capillary hemorrhage. Then all of them were randomly divided into 6 groups: blank control, negative control group, 0.5, 1, 2 and 4 kU/L (U/ml) BX group. The hemostatic time and bleeding volume were observed to compare the hemostatic effect of each group. Haematoxylin-eosin, Masson staining and immunohistochemistry were performed to assure adventitia removed. RESULTS: It was feasible to remove vascular adventitia with collagenase digestion and mechanical dissection. The hemostatic time and bleeding volume were significantly different (P < 0.05) from 0.5 U/ml BX group [(97 ± 20)s,(0.102 ± 0.013)g/cm(2)] of the negative control group[(143 ± 33)s,(0.130 ± 0.023) g/cm(2)]. With the increase of BX concentration, there was a significant difference (P < 0.05) between 2 U/ml BX group (32 ± 13,0.056 ± 0.015) and 1 U/ml BX group (32 ± 13,0.056 ± 0.015), but there was no statistical significance (P > 0.05) between 2 U/ml BX group and 4 U/ml BX group (28 ± 14,0.053 ± 0.012). Thus, the best topical hemostatic concentration of BX was 2 U/ml. CONCLUSION: The topical hemostatic effect of batroxobin is reliable in small area of blood oozing.