Risk prediction of second primary malignancies in patients after rectal cancer: analysis based on SEER Program.

BACKGROUND: This study will focus on exploring the clinical characteristics of rectal cancer (RC) patients with Second Primary Malignancies (SPMs) and constructing a prognostic nomogram to provide clinical treatment decisions. METHODS: We determined the association between risk factors and overall survival (OS) while establishing a nomogram to forecast the further OS status of these patients via Cox regression analysis. Finally, we evaluated the performance of the prognostic nomogram to predict further OS status. RESULTS: Nine parameters were identified to establish the prognostic nomogram in this study, and, the C-index of the training set and validation set was 0.691 (95%CI, 0.662-0.720) and 0.731 (95%CI, 0.676-0.786), respectively. The calibration curve showed a high agreement between the predicted and actual results, and the receiver operating characteristic (ROC) curves verified the superiority of our model for clinical usefulness. In addition, the nomogram classification could more precisely differentiate risk subgroups and improved the discrimination of SPMs' prognosis. CONCLUSIONS: We systematically explored the clinical characteristics of SPMs after RC and constructed a satisfactory nomogram.

Amidoxime Modified UiO-66@PIM-1 Mixed-Matrix Membranes to Enhance CO2 Separation and Anti-Aging Performance.

Mixed matrix membranes (MMMs) generally have some fatal defects, such as poor compatibility between the two phases leading to non-selective pores. In this work, PIM-1 was chosen as the polymer matrix, and UiO-66 modified with amidoxime (UiO-66-AO) was used as the filler to prepare the MMMs. In the MMMs, the amino and hydroxyl groups on UO-66-AO form a rich hydrogen bond network with the N and O atoms in the polymer PIM-1 chain to improve the compatibility between the polymer matrix and the filler. In addition, the selective adsorption of CO2 by the amidoxime group can promote the transport of CO2 in the membrane, which enhances the gas selectivity. The CO2 permeability and CO2/N2 selectivity of UiO-66-AO@PIM-1 MMMs are increased by 35.2% and 45.2% compared to pure PIM-1 membranes, reaching 7535.5 Barrer and 26.9, surpassing the Robeson Upper Bound (2008) and close to the 2019 Upper Bound. After 38 days of the aging experiment, the CO2 permeability is approximately 74% of the original. The results show that the addition of UiO-66-AO has an obvious effect on improving the aging properties of the membrane. The UiO-66-AO@PIM-1 MMMs have a bright prospect for CO2 separation in the future.

Fabrication of a Cation-Exchange Membrane via the Blending of SPES/N-Phthaloyl Chitosan/MIL-101(Fe) Using Response Surface Methodology for Desalination.

In the present work, a novel mixed matrix cation exchange membrane composed of sulfonated polyether sulfone (SPES), N-phthaloyl chitosan (NPHCs) and MIL-101(Fe) was synthesized using response surface methodology (RSM). The electrochemical and physical properties of the membrane, such as ion exchange capacity, water content, morphology, contact angle, fixed ion concentration and thermal stability were investigated. The RSM based on the Box-Behnken design (BBD) model was employed to simulate and evaluate the influence of preparation conditions on the properties of CEMs. The regression model was validated via the analysis of variance (ANOVA) which exhibited a high reliability and accuracy of the results. Moreover, the experimental data have a good fit and high reproducibility with the predicted results according to the regression analysis. The embedding of MIL-101(Fe) nanoparticles contributed to the improvement of ion selective separation by forming hydrogen bonds with the polymer network in the membrane. The optimum synthesis parameters such as degree of sulfonation (DS), the content of SPES and NPHCs and the content of MIL-101(Fe) were acquired to be 30%, 85:15 and 2%, respectively, and the corresponding desalination rate of the CEMs improved to 136% while the energy consumption reduced to 90%. These results revealed that the RSM was a promising strategy for optimizing the preparation factors of CEMs and other similar multi-response optimization studies.

Influential Mechanism of Natural Organic Matters with Calcium Ion on the Anion Exchange Membrane Fouling Behavior via xDLVO Theory.

The fouling mechanism of the anion exchange membrane (AEM) induced by natural organic matter (NOM) in the absence and presence of calcium ions was systematically investigated via the extended Derjaguin-Landau-Verwey-Overbeek (xDLVO) approach. Sodium alginate (SA), humic acid (HA), and bovine serum albumin (BSA) were utilized as model NOM fractions. The results indicated that the presence of calcium ions tremendously aggravated the NOM fouling on the anion exchange membrane because of Ca-NOM complex formation. Furthermore, analysis of the interaction energy between the membrane surface and foulants via xDLVO revealed that short-range acid-base (AB) interaction energy played a significant role in the compositions of interaction energy during the electrodialysis (ED) process. The influence of NOM fractions in the presence of calcium ions on membrane fouling followed the order: SA > BSA > HA. This study demonstrated that the interaction energy was a dominating indicator for evaluating the tendency of anion exchange membranes fouling by natural organic matter.

A preliminary study of KAT2A on cGAS-related immunity in inflammation amplification of systemic lupus erythematosus.

Previous studies demonstrated that cGAS pathway is related to the inflammation amplification in a variety of autoimmune diseases. Lysine acetyltransferase family (KATs) can regulate the nuclear transcription or cytoplasmic activation of cGAS through different mechanisms. However, its role and related immunity patterns in systemic lupus erythematosus (SLE) have not been explored. In this study, RNA-seq and scRNA-seq profiling were performed for peripheral blood mononuclear cells (PBMCs) from patients with SLE. R packages were used for bioinformatic analysis. Cell culture, RT-PCR, western blotting, immunofluorescence, immunohistochemistry, and ELISA were used to explore gene expression in vitro or clinical specimens. Plasmid transfection and mass spectrometry were used to detect protein modifications. Eight acetyltransferase and deacetylase family members with significantly differential expression in SLE were found. Among them, KAT2A was abnormally upregulated and positively correlated with disease activity index. Further, KAT2A-cGAS pathway was aberrantly expressed in specific immune cell subsets in SLE. In vitro studies showed KAT2A modulated cGAS through increasing expression and post-translational modification. Our research provides novel insights for accurately positioning specific immune-cell subgroups in which KAT2A-cGAS reaction mainly works and KAT2A regulation patterns.

The Protective of Baicalin on Myocardial Ischemia-Reperfusion Injury.

BACKGROUND: The aim of this study was to explore the inhibitory effect of baicalin on myocardial apoptosis induced by Ischemia-Reperfusion (I/R). METHODS: Sprague Dawley rats' heart and myocardial cells I/R model were established in vivo and vitro, then 100 mg/kg and 10 µmol/l baicalin were administrated, respectively. The experiment was randomly divided into 4 groups (n=10): Control; I/R; IR+DMEM; and I/R+baicalin groups. Postoperation, the Left Ventricular (LV) End-Diastolic Pressure (LVEDP), the maximum velocity of LV contraction (dP/dtmax) and the maximum velocity of LV diastole (dP/dtmin) were recorded by the transthoracic echocardiography; the myocardial apoptosis percentage was analyzed by Annexin VFITC/ PI and TUNEL staining, and the apoptosis gene and protein were detected by RT-PCR and western blot. Furthermore, the protein expression of the calcium-sensing receptor (CaSR) and ERK1/2 phosphorylation were observed by western blot and Fura-2-acetoxymethyl ester. Moreover, primary rats' cardiomyocytes were cultured and ERK1/2 specific inhibitor PD98059 was added to the culture medium. The cell survival rate, vitality and apoptosis were detected by MTT, lactate dehydrogenase (LDH) and TUNEL staining assay Kit, respectively. RESULTS: Our present study showed that baicalin significantly improved LV hemodynamic parameters and myocardial apoptosis in myocardial I/R injury rats. Furthermore, we found that baicalin could down-regulate the protein expression of CaSR, but up-regulate the protein expression of ERK1/2. Furthermore, when the cells were pretreated with ERK1/2 inhibitor PD98059, the cells survival rate significantly decreased, but LDH activity and apoptosis significantly increased. The results indicated that the effect of baicalin on myocardial I/R injury could be inhibited by ERK1/2 inhibitor. CONCLUSION: In conclusion, our data suggests that baicalin attenuates I/R-induced myocardial injury maybe through the suppression of the CaSR/ERK1/2 signaling pathway.

Mesenchymal stromal cell-derived exosomes improve pulmonary hypertension through inhibition of pulmonary vascular remodeling.

BACKGROUND: Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling, right ventricular hypertrophy and failure. So far no effective treatment exists for this disease; hence, novel approaches are urgently needed. The aim of the present research was to observe the treatment effect of mesenchymal stromal cell derived exosomes and reveal the mechanism. METHODS: Monocrotaline (MCT)-induced PH in rats and hypoxia-induced cell damage model were established, respectively. Exosomes derived from the supernatant of human umbilical cord mesenchymal stem cells (MSC-exo) were injected into MCT-PH model rat or added into the cells cultured medium. Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot methods were used in vivo and vitro. RESULTS: The results showed that MSC-exo could significantly attenuate right ventricular (RV) hypertrophy and pulmonary vascular remodelling in MCT-PH rats. In the cell culture experiments, we found that MSC-exo could significantly inhibit hypoxia-induced pulmonary arterial endothelial cell (PAEC) apoptosis and pulmonary arterial smooth muscle cells (PASMC) proliferation. Furthermore, the pulmonary arterioles endothelial-to-mesenchymal transition (EndMT) was obviously suppressed. Moreover, the present study suggest that MSC-exo can significantly upregulate the expression of Wnt5a in MCT-PH rats and hypoxic pulmonary vascular cells. Furthermore, with Wnt5a gene silencing, the therapeutic effect of MSC-exo against hypoxia injury was restrained. CONCLUSIONS: Synthetically, our data provide a strong evidence for the therapeutic of MSC-exo on PH, more importantly, we confirmed that the mechanism was associated with up-regulation of the expression of Wnt5a. These results offer a theoretical basis for clinical prevention and treatment of PH.

[Expression of MCP-1 in renal tissues of patients with IgA nephropathy].

OBJECTIVE: To investigate the differential expression of monocyte chemoattractant protein-1 (MCP-1) in renal biopsy tissues of patients with IgA nephropathy, and to analyse the association between these 2 markers and their effect on various pathologic types of IgA nephropathy. METHODS: According to pathologic type, 88 renal biopsy tissues of patients with IgA nephropathy were divided into 4 groups:a minimal change group,a mesangial proliferative glomerulonephritis group, a focal sclerosing glomerulonephritis group, and a diffused sclerosing glomerulonephritis group. Immunohistochemical staining was used to detect the in situ expression of MCP-1 and CD68 on renal biopsy tissues. The expression levels were semi-quantified by image analysis and clinical data were collected from the patients. RESULTS: The differences in glomerular MCP-1 expressions were not statistically significant among all groups, while the tubulointerstitial MCP-1 expressions were statistically different among the 4 groups, with the average scores of 1.43+/-0.60, 5.98+/-0.92, 10.60+/-0.76 and 11.65+/-0.39 for minimal change group, mesangial proliferative glomerulonephritis group, focal sclerotic glomerulonephritis, and diffused sclerotic glomerulonephritis group, respectively. The tubular and interstitial CD68 scores were 0.75+/-0.71, 5.87+/-0.96, 10.42+/-0.61, and 11.40+/-0.49 for the 4 groups, with significant differences in both MCP-1 and CD68 among the 4 groups. Correlation analysis indicated a positive correlation between tubulointerstitial MCP-1 and CD68 (r=0.688, P<0.01). MCP-1 in tubulointerstitial was significantly correlated with 24 h urinary protein excretion(r=0.531, P<0.01). CONCLUSION: MCP-1 plays a critical role in macrophage infiltration in the kidney. MCP-1 is associated with the severity of tubulointerstitial damage and clinical prognosis.