Characterization of Duodenal Microbiota in Patients with Acute Pancreatitis and Healthy Controls.

OBJECTIVE: The small intestinal bacterial overgrowth (SIBO) in acute pancreatitis correlates with the severity of the disease. However, corresponding studies on the microbial composition of the duodenal mucosa of patients are uncommon. METHODS: Duodenal mucosal biopsies were collected by gastroscopy from 16 patients with mild acute pancreatitis (the Ap group) and 16 healthy individuals (the control group) and subjected to histological studies as well as bacterial 16S rRNA gene sequencing. Caerulein and L-arginine were used to induce mild acute pancreatitis (MAP) and severe acute pancreatitis (SAP) in mice, respectively, and their pancreas and duodenum were collected for histological studies. RESULTS: H&E analysis displayed no significant pathological damage in the descending duodenum of patients with acute pancreatitis compared with that of the controls. Immunofluorescence and Real-time PCR revealed that the expressions of tight junction proteins (TJPs) in duodenal mucosa were decreased in acute pancreatitis. The results of the alpha diversity analysis revealed no significant difference between the two groups, while LEfSe and the random forest revealed a few differences, indicating that the descending duodenum mucosal microbiota changed slightly in patients with mild acute pancreatitis. We observed the pathological changes and the expression of TJPs in the duodenum in the three groups of mice and found that SAP mice had more severe pathological damage in the duodenum. Furthermore, the expression of TJPs in the duodenum was lower in the MAP and SAP groups of mice compared to control mice, but it was similar in both groups. CONCLUSION: Patients with mild acute pancreatitis had mild duodenal barrier dysfunction and slight changes in duodenal mucosal microbiota.

Regional abnormalities of spontaneous brain activity in migraine: A coordinate-based meta-analysis.

Many resting-state functional magnetic resonance imaging (rs-fMRI) studies have explored abnormal regional spontaneous brain activity in migraine. However, these results are inconsistent. To identify the consistent regions with abnormal neural activity, we meta-analyzed these studies. We gathered whole-brain rs-fMRI studies measuring differences in the amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), or regional homogeneity (ReHo) methods. Then, we performed a voxel-wise meta-analysis to identify consistent abnormal neural activity in migraine by anisotropic effect size seed-based d mapping (AES-SDM). To confirm the AES-SDM meta-analysis results, we conducted two meta-analyses: activation likelihood estimation (ALE) and multi-level kernel density analysis (MKDA). We found that migraine showed increased regional neural activities in the bilateral postcentral gyrus (PoCG), left hippocampus (HIP.L), right pons, left superior frontal gyrus (SFG.L), triangular part of right inferior frontal gyrus (IFGtriang.R), right middle frontal gyrus (MFG.R), and left precentral gyrus (PreCG.L) and decreased regional intrinsic brain activities were exhibited in the right angular gyrus (ANG.R), left superior occipital gyrus (SOG.L), right lingual gyrus (LING.R). Moreover, the meta-analysis of ALE further validated the abnormal neural activities in the PoCG, right pons, ANG.R, and HIP. Meta-regression demonstrated that headache intensity was positively associated with the abnormal activities in the HIP.L, ANG.R, and LING.R. These findings suggest that migraine is associated with abnormal spontaneous brain activities of some pain-related regions, which may contribute to a deeper understanding of the neural mechanism of migraine.

The impact of Helicobacter pylori infection and eradication therapy containing minocycline and metronidazole on intestinal microbiota.

BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with remodeling of gut microbiota. Many studies have found H. pylori infection and eradication therapy can alter the gut microbiota. However, few studies explored the impact of eradication therapy containing minocycline and metronidazole on gut microbiota. AIM: The objective of the present study was to explore the changes of gut microbiota after H. pylori infection. Besides, learn more about the dynamic changes of gut microbiota during different stages of eradication treatment containing minocycline, metronidazole, bismuth agents and proton pump inhibitors. METHODS: Sixty stool samples from the patients with H. pylori infection before eradication, 14 and 42 days after eradication, and ten stool samples from non-infected individuals were collected. Subsequently, we performed 16S rRNA gene amplicon sequencing to analyze these samples, and the results were evaluated by using alpha diversity, beta diversity and microbial composition analyses. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was also used to predict the metabolic pathways according to the Kyoto Encyclopedia of Genes and Genomes database. RESULTS: The alpha and beta diversity of the microbiota changed significantly in H. pylori infected individuals, but returned to baseline 42 days after eradication therapy. At the genus level, the abundances of Bacteroidetes, [Ruminococcus]_gnavus_group, Ruminococcaceae_Incertae_Sedis, Tuzzrealla, Butyricicoccus were significantly lower in the H. pylori infected group. Bacterial abundance was also dynamically changing during eradication treatment. In addition, PICRUST analysis found the levels of uronic acid metabolism, uncharacterized transport system, and biosynthesis of unsaturated fatty acids were higher in H. pylori infected individuals than in the non-infected group. CONCLUSIONS: Intestinal microbiota diversity, composition, functional predictions altered significantly after H. pylori infection, and gradually returned to healthy control levels after the application of eradication therapy containing minocycline and metronidazole in one month and a half.

Sortilin deletion in the prefrontal cortex and hippocampus ameliorates depressive-like behaviors in mice via regulating ASM/ceramide signaling.

Major depressive disorder (MDD) is a common psychiatric disorder characterized by persistent mood despondency and loss of motivation. Although numerous hypotheses have been proposed, the possible pathogenesis of MDD remains unclear. Several recent studies show that a classic transporter protein, sortilin, is closely associated with depression. In the present study, we investigated the role of sortilin in MDD using a well-established rodent model of depression. Mice were subjected to chronic unpredictable mild stress (CUMS) for 6 weeks. We showed that the expression levels of sortilin were significantly increased in the prefrontal cortex and hippocampus of CUMS mice. The depressive-like behaviors induced by CUMS were alleviated by specific knockdown of sortilin in the prefrontal cortex and hippocampus. We revealed that sortilin facilitated acid sphingomyelinase (ASM)/ceramide signaling, which activated RhoA/ROCK2 signaling, ultimately causing the transformation of dendritic spine dynamics. Specific overexpression of sortilin in the prefrontal cortex and hippocampus induced depressive-like behaviors, which was mitigated by injection of ASM inhibitor SR33557 (4 µg/µL) into the prefrontal cortex and hippocampus. In conclusion, sortilin knockdown in the prefrontal cortex and hippocampus plays an important role in ameliorating depressive-like behavior induced by CUMS, which is mainly evidenced by decreasing the trafficking of ASM from the trans-Golgi network to the lysosome and reducing the ceramide levels. Our results provide a new insight into the pathology of depression, and demonstrate that sortilin may be a potential therapeutic target for MDD.

Cell-free DNA in blood and urine as a diagnostic tool for bladder cancer: a meta-analysis.

OBJECTIVE: To assess the diagnostic performance of cell-free DNA assays in the detection of bladder cancer. PATIENTS AND METHODS: The quality of the studies included in this meta-analysis was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Statistical analyses were performed using the software RevMan 5.3 and Stata 14.0. We assessed the pooled sensitivity and specificity, positive/negative likelihood ratios (PLRs/NLRs), diagnostic odds ratios (DORs), and corresponding 95% confidence intervals (95% CIs). Summary receiver operating characteristic curve (ROC curve) and area under the curve (AUC) were used to summarize the overall test performance. Heterogeneity and publication bias were also examined. RESULTS: Eleven studies included 802 bladder cancer patients and 668 controls met the eligibility criteria. The overall diagnostic accuracy was measured as follows: sensitivity 0.71 (95% CI = 0.64-0.77), specificity 0.78 (95% CI = 0.70-0.85), PLR 3.3 (95% CI = 2.4-54.5), NLR 0.37 (95% CI = 0.30-0.46), DOR 9 (95% CI = 6-14), and AUC 0.80 (95% CI = 0.77-0.83). Subgroup analysis suggested that ethnicity significantly accounted for the heterogeneity of specificity. The Deeks' funnel plot asymmetry test (P = 0.97) suggested no potential publication bias. CONCLUSIONS: Cell-free DNA has a high diagnostic value in bladder cancer.

A highly integrated precision nanomedicine strategy to target esophageal squamous cell cancer molecularly and physically.

The prognosis of esophageal squamous cell carcinoma is poor. We hereby presented a highly integrated and clinically relevant precision nanomedicine strategy to target ESCC molecularly and physically for significant improvement of the treatment efficacy. We firstly identified PI3K overexpression in patient samples and its relation to poor patient survival. With our highly versatile tumor-targeted drug delivery platform (DCM), we were able to load a potent but toxic docetaxel (DTX) and a PI3K inhibitor (AZD8186) with favorable physical properties. The combination of the DTX-DCM and AZD8186-DCM showed a highly efficacious and synergistic anti-tumor effect and decreased hematotoxicity. A pro-apoptotic protein, Bax was significantly upregulated in ESCC cells treated with combination therapy compared to that with monotherapy. This study utilized a highly integrated precision nano-medicine strategy that combines the identification of cancer molecular target from human patients, precision drug delivery and effective combination therapy for the development of better ESCC treatment.

Nanoformulated paclitaxel and AZD9291 synergistically eradicate non-small-cell lung cancers in vivo.

AIM: This study aims to develop new nanoformulations of EGFR T790M targeted inhibitor AZD9291 and paclitaxel (PTX) for combination therapy of lung cancer. MATERIALS & METHODS: We prepared and characterized PTX- and AZD9291-loaded disulfide cross-linking micelles (DCMs), and evaluate their combination effect and toxicity in vitro and in lung cancer-bearing mice. RESULTS: Drug-loaded DCMs were relatively small in size, and possessed glutathione-responsive drug release. The combination of PTX-DCMs and AZD92921-DCMs exhibited strong synergistic effects in both cell line and in vivo without additional toxicity. Molecular studies demonstrated the synergistic modification in both IKB-α/NF-κB/Bcl-2 and EGFR/Akt pathways. CONCLUSION: The combination of DCM-loaded AZD9291 and PTX could potentially offer more effective and less toxicity treatment options for lung cancer patients.

[Adsorption Behavior of Pb(â ¡) Ion Imprinted Magnetic Composite Adsorbent in Aqueous Solution by FAAS].

Pb(Ⅱ) Ion Imprinted Magnetic Composite Adsorbent (Pb(Ⅱ)-MICA) was prepared for the quick separation of Pb(Ⅱ) from aqueous solutions by bulk polymenrization with chitosan as the functional monomer, the magnetic iron oxide nano-particles as carrier and epichlorohydrin as the cross-link agent. The Pb(Ⅱ)-MICA and MNICA were characterized by FTIR. The Effects of the adsorption process including pH, contact time, initial concentration and temperature were investigated by FAAS. It was found that with the increasing of PH value, the adsorption capacity of Pb(Ⅱ)-MICA for Pb(Ⅱ) reached the peak in the range of pH 5.0～6.0. The maximum adsorption capacity was 32.48 mg·g-1 when the adsorption time was up to 120 min. The relative selectivity coefficient of Pb(Ⅱ) and other metal ion on Pb(Ⅱ) -MICA were 28.11, 91.14, 76.54, 33.06 times compared with MNICA. The results show that the Pb(Ⅱ)-MICA displayed strong affinity for Pb(Ⅱ) in the solution and exhibited selectivity for Pb(Ⅱ) ion in the presence of Cu2+，Cd2+，Ni2+ and Zn2+. The Langmuir adsorption isotherm models were fit to the adsorption equilibrium data well (r2=1, the saturation adsorption capacities were 33.87 mg·g-1). The adsorption dynamics and thermodynamics of Pb(Ⅱ) -MICA for Pb(Ⅱ) were investigated, the results indicated a Langmuir mono-layer mode process of Pb(Ⅱ) on the Pb(Ⅱ)-MICA was dominated by chemical action. An exothermic and spontaneous adsorption process of Pb(Ⅱ) on the Pb(Ⅱ)-MICA was driven by enthalpy.

[Synthesis of crosslinked polymer containing beta-cyclodextrin and its adsorption for Pb2+ and Zn2+ studied by AAS].

Crosslinked copolymer(AA/beta-CD-AA/ABE) containing beta-cyclodextrin was synthesized by microwave heating with acylation, allyl-biphenyl-ether(ABE), crylic acid(AA) as monomer and N, N-methylenebisacrylamide (MBA) as cross-linking agent, and characterized by means of FTIR. The adsorption of Pb2+ and Zn2+ on the synthesized copolymer and the factors (adsorption time, pH and temperature) which affect the adsorption capacity were investigated by atomic absorption spectrometry (AAS) as the detection means. The results show that the optimum experimental conditions of adsorption: 35 degrees C, 2 h and pH 2-3, adsorbance Q for Pb2+ reached maximum 29.5 mg x g(-1); 30 degrees C, 3 h and pH 3-4, adsorbance Q for Zn2+ reached maximum 43.7 mg x g(-1); the adsorption equilibriums for Pb2+ and Zn2+ fit the Freundlich on the whole.