Intratumour microbiome of pancreatic cancer

Pancreatic cancer is a high mortality malignancy with almost equal mortality and morbidity rates.Both normal and tumour tissues of the pancreas were previously considered sterile.In recent years,with the development of technologies for highthroughput sequencing,a variety of studies have revealed that pancreatic cancer tissues contain small amounts of bacteria and fungi.The intratumour microbiome is being revealed as an influential contributor to carcinogenesis.The intratumour microbiome has been identified as a crucial factor for pancreatic cancer progression,diagnosis,and treatment,chemotherapy resistance,and immune response.A better understanding of the biology of the intratumour microbiome of pancreatic cancer contributes to the establishment of better early cancer screening and treatment strategies.This review focuses on the possible origins of the intratumour microbiome in pancreatic cancer,the intratumour localization,the interaction with the tumour microenvironment,and strategies for improving the outcome of pancreatic cancer treatment.Thus,this review offers new perspectives for improving the prognosis of pancreatic cancer.

Immuno-oncology-microbiome axis of gastrointestinal malignancy

Research on the relationship between the microbiome and cancer has been controversial for centuries.Recent works have discovered that the intratumor microbiome is an important component of the tumor microenvironment(TME).Intratumor bacteria,the most studied intratumor microbiome,are mainly localized in tumor cells and immune cells.As the largest bacterial reservoir in human body,the gut microbiome may be one of the sources of the intratumor microbiome in gastrointestinal malignancies.An increasing number of studies have shown that the gut and intratumor microbiome play an important role in regulating the immune tone of tumors.Moreover,it has been recently proposed that the gut and intratumor microbiome can influence tumor progression by modulating host metabolism and the immune and immune tone of the TME,which is defined as the immuno-oncology-microbiome(IOM)axis.The proposal of the IOM axis provides a new target for the tumor microbiome and tumor immunity.This review aims to reveal the mechanism and progress of the gut and intratumor microbiome in gastrointestinal malignancies such as esophageal cancer,gastric cancer,liver cancer,colorectal cancer and pancreatic cancer by exploring the IOM axis.Providing new insights into the research related to gastrointestinal malignancies.

Percolation transitions in edge-coupled interdependent networks with directed dependency links

We propose a model of edge-coupled interdependent networks with directed dependency links(EINDDLs)and develop the theoretical analysis framework of this model based on the self-consistent probabilities method.The phase transition behaviors and parameter thresholds of this model under random attacks are analyzed theoretically on both random regular(RR)networks and Erd¨os-Renyi(ER)networks,and computer simulations are performed to verify the results.In this EINDDL model,a fractionβof connectivity links within network B depends on network A and a fraction(1-β)of connectivity links within network A depends on network B.It is found that randomly removing a fraction(1-p)of connectivity links in network A at the initial state,network A exhibits different types of phase transitions(first order,second order and hybrid).Network B is rarely affected by cascading failure whenβis small,and network B will gradually converge from the first-order to the second-order phase transition asβincreases.We present the critical values ofβfor the phase change process of networks A and B,and give the critical values of p andβfor network B at the critical point of collapse.Furthermore,a cascading prevention strategy is proposed.The findings are of great significance for understanding the robustness of EINDDLs.

CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric carcinoma

AIM To investigate the role of CXC chemokine receptor(CXCR)-7 and CXCL12 in lymph node and liver metastasis of gastric carcinoma.METHODS In 160 cases of gastric cancer, the expression of CXCR7 and CXCL12 in tumor and matched tumoradjacent non-cancer tissues, in the lymph nodes around the stomach and in the liver was detected using immunohistochemistry to analyze the relationship between CXCR7/CXCL12 expression and clinicopathological features and to determine whether CXCR7 and CXCL12 constitute a biological axis to promote lymph node and liver metastasis of gastric cancer. Furthermore, the CXCR7 gene was silenced and overexpressed in human gastric cancer SGC-7901 cells, and cell proliferation, migration and invasiveness were measured by the MTT, wound healing and Transwell assays, respectively. RESULTS CXCR7 expression was up-regulated in gastric cancer tissues(P = 0.011). CXCR7/CXCL12 expression was significantly related to poor tumor differentiation, high tumor stage and lymph node(r = 0.338, P = 0.000) and liver metastasis(r = 0.629, P = 0.000). The expression of CXCL12 in lymph node and liver metastasis was higher than that in primary gastric cancer tissues(χ2 = 6.669, P = 0.010; χ2 = 25379, P = 0.000), and the expression of CXCL12 in lymph node and liver metastasis of gastric cancer was consistent with the positive expression of CXCR7 in primary gastric cancer(r = 0.338, P = 0.000; r = 0.629, P = 0.000). Overexpression of the CXCR7 gene promoted cell proliferation, migration and invasion. Silencing of the CXCR7 gene suppressed SGC-7901 cell proliferation, migration and invasion. Human gastric cancer cell lines expressed CXCR7 and showed vigorous proliferation and migratory responses to CXCL12.CONCLUSION The CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric cancer. CXCR7 is considered a potential therapeutic target for the treatment of gastric cancer.

Protective effect of telmisartan on rats with renal failure and its mechanism

Objective:To study the protective effect of telmisartan on rats with renal failure and its mechanism.Methods:60 Wistar rats were chosen as study objective,and were divided into4 groups randomly:15 in group A(sham operation group).15 in group B(model group),15 in group C(telmisartan group) and 15 in group D(telmisartan+GW9962 group).The difference of survival rate,blood-urine biochemical indexes,renal pathological change,and the expression level of PPAR γ and nNOS were ompared.Results:After 12 weeks,the survival rate of group A was 93.33% (14/15),that of group B was 46.67% (7/15),that of group C was86.67% (13/15),that of group D was 60.00% (9/15),and the difference among 4 groups had statistical significance(P<0.05).After 1 week,the difference of Scr,that of BUN and that of24 h protein urine among 4 groups was not statistical significant(P>0.05);after 3 weeks,6 weeks and 12 weeks,these difference was statistical significant(P<0.05).The difference of blood-urine biochemical indexes,that of renal pathological change,and that of the expression level of PPAR γ and nNOS was statistical significant(P<0.05).Conclusions:Telmisartan has protective effect on renal failure caused by 5/6 nephrectomy,which might be relative to the expression level of PPAR γ and nNOS.

Brain protection of AC in PTZ-induced epileptic rats

Objective:To investigate the neuroprotective effect and mechanism of Acteoside(AC)on brain injury in epileptic rats.Methods:30 Sprague-Dawlay rats(SPF grade,healthy males,about 200g)were randomly divided into epilepsy group,AC group and blank control group.The epileptic group and the AC group were given 28 days of intraperitoneal injection of pentaerythritazine(PTZ),and the remaining groups were given normal saline injection.The changes of electroencephalogram(EEG),learning and memory ability,pathological changes of brain tissue,superoxide dismutase(SOD)and malondialdehyde(MDA)were observed in all rats.Results:Compared with the epilepsy group,the AC group showed significantly reduced degeneration and necrosis of nerve cells in brain tissue,significantly improved learning and memory ability,and the EEG was dominated by wavelet and slow wave,replacing the typical spike and spike waves.SOD increased and MDA decreased in oxygen radical(P<0.05).Conclusions:Epilepsy are closely related to Oxidative stress.AC can play a protective role in the brain by improving EEG,learning and memory ability,regulating changes in SOD and MDA content,and inhibiting the generation of oxygen free radicals.

PTSD:Past,present and future implications for China

There has been a long history since human beings began to realize the existence of post-traumatic symptoms.Posttraumatic stress disorder(PTSD),a diagnostic category adopted in 1980 in the Diagnostic and Statistical Manual of Mental Disorders-III,described typical clusters of psychiatric symptoms occurring after traumatic events.Abundant researches have helped deepen the understanding of PTSD in terms of epidemiological features,biological mechanisms,and treatment options.The prevalence of PTSD in general population ranged from 6.4%to 7.8%and was significantly higher among groups who underwent major public traumatic events.There has been a long way in the studies of animal models and genetic characteristics of PTSD.However,the high comorbidity with other stress-related psychiatric disorders and complexity in the pathogenesis of PTSD hindered the effort to find specific biological targets for PTSD.Neuroimage was widely used to elucidate the underlying neurophysiological mechanisms of PTSD.Functional MRI studies have showed that PTSD was linked to medial prefrontal cortex,anterior cingulate cortex and sub-cortical structures like amygdala and hippocampus,and to explore the functional connectivity among these brain areas which might reveal the possible neurobiological mechanism related to PTSD symptoms.For now,cognitive behavior therapy-based psychotherapy,including combination with adjunctive medication,showed evident treatment effects on PTSD.The emergence of more effective PTSD pharmacotherapies awaits novel biomarkers from further fundamental research.Several natural disasters and emergencies have inevitably increased the possibility of suffering from PTSD in the last two decades,making it critical to strengthen PTSD research in China.To boost PTSD study in China,the following suggestions might be helpful:(1)establishing a national psychological trauma recover project,and(2)exploring the mechanisms of PTSD with joint effort and strengthening the indigenized treatment of PTSD.

Constraining self-interacting dark matter with the full dataset of PandaX-II

Self-interacting dark matter(SIDM)is a leading candidate proposed to solve discrepancies between predictions of the prevailing cold dark matter theory and observations of galaxies.Many SIDM models predict the existence of a light force carrier that mediates strong dark matter self-interactions.If the mediator couples to the standard model particles,it could produce characteristic signals in dark matter direct detection experiments.We report searches for signals of SIDM models with a light mediator using the full dataset of the PandaX-II experiment,basing on a total exposure of 132 tonne-days.No significant excess over background is found,and our likelihood analysis leads to a strong upper limit on the dark matter-nucleon coupling strength.We further combine the PandaX-II constraints and those from observations of the light element abundances in the early universe,and show that direct detection and cosmological probes can provide complementary constraints on dark matter models with a light mediator.