Cadmium exposure impairs pancreatic ß-cell function and exaggerates diabetes by disrupting lipid metabolism.

Cadmium is known as an environmental pollutant that contributes to pancreatic damage and the pathogenesis of diabetes. However, less attention has been devoted to elucidating the mechanisms underlying Cd-induced pancreatic ß-cell dysfunction and the role of Cd toxicity in the development of diabetes. In this study, we demonstrated that exposure to Cd caused remarkable pancreatic ß-cell dysfunction and death, both in vitro and in vivo. Lipidomic analysis of Cd-exposed pancreatic ß-cells using high-resolution mass spectrometry revealed that Cd exposure altered the profile and abundance of lipids. Cd exposure induced intracellular lipid accumulation, promoted lipid biogenesis, elevated pro-inflammatory lipid contents and inhibited lipid degradation. Furthermore, Cd exposure upregulated the expression levels of TNF-α, IL-1ß and IL-6 in pancreatic ß-cells and elevated the TNF-α, IL1-ß and IL-6 levels in the serum and pancreas. Taken together, the results of our study demonstrated that environmental relevant Cd exposure causes pro-inflammatory lipids elevation and insulin secretion dysfunction in ß-cells and hence exaggerates diabetes development. Combined exposure to environmental hazardous chemicals might markedly increase the probability of developing diabetes in humans. This study provides new metabolic and pharmacological targets for antagonizing Cd toxicity.

Early Activation of Myeloid-Derived Suppressor Cells Participate in Sepsis-Induced Immune Suppression via PD-L1/PD-1 Axis.

Background: Myeloid derived suppressor cells (MDSCs) have been reported to keep elevating during sepsis. The current study was performed to investigate the immunosuppressive effect of MDSCs and their subsets with the underlying mechanisms. Methods: The immunosuppressive status was manifested by the apoptosis of splenocytes, quantity of T cells and PD-1 expression. The dynamics of quantity and PD-L1 level of MDSCs and the subsets were determined over time. The subset of MDSCs with high PD-L1 level was co-cultured with T cells to observe the suppressive effect. Results: Abdominal abscess was observed after 7 days post-sepsis. Five biomarkers related to organ functions were all significantly higher in the CLP group. The survival rate was consistent with the middle grade severity of sepsis model. Apoptosis of splenocytes increased over time during sepsis; CD4 + T cell decreased from day 1 post-sepsis; CD8+ T cells significantly reduced at day 7. The PD-1 expression in spleen was upregulated from an early stage of sepsis, and negatively related with the quantity of T cells. MDSCs were low at day 1 post-sepsis, but increased to a high level later; the dynamics of PMN-MDSC was similar to MDSCs. PD-L1 on MDSCs was highest at day 1 post-sepsis; PMN-MDSC was the main subset expressing PD-L1. The PMN-MDSC with high PD-L1 expression level extracted on day 1 after surgery from CLP mice significantly inhibited the proliferation of T cells. Conclusions: Sepsis-induced immunosuppression is initiated from a very early stage, a high expression level of PD-L1 on MDSCs and the main subset, PMN-MDSC might play a critical role suppressive role on T cells through PD-L1/PD-1 axis.

The life-saving emergency thoracic endovascular aorta repair management on suspected aortoesophageal foreign body injury.

BACKGROUND: Fatal aortic rupture caused by esophageal foreign body (EFB), is associated with a high mortality, but can be prevented by thoracic endovascular aorta repair (TEVAR) that performed increasingly as technology improves. This study aims to investigate the cause, management and prognosis of suspected penetrating aortoesophageal foreign body injury. METHODS: Twelve cases who met the criteria were enrolled in this study. The demographic and clinical data were reviewed for evaluating the characteristics of EFB. RESULTS: Among 12 cases enrolled, 7 were males and 5 were females, with an age 27-86 years. The distance of EFB from aorta (DFA) of 7 cases were less than or equal to 0 mm, 5 cases were 0-2 mm. Eleven cases were managed with TEVAR, only one case was with open surgery standby but finally treated by flexible endoscopy (FE) successfully, without TEVAR. In group with TEVAR, EFB of 7 cases were successfully removed by rigid endoscopy (RE), and one of them was failed at the first RE treatment. EFB of 2 cases were successfully removed by open surgery with TEVAR, and other 9 cases were managed by endoscopies with TEVAR. The mean length of stay of hospitalization (LOS) and length of ICU stay of patients treated by open surgery with TEVAR (18.50±2.12 days and 5.50±0.71 days) was significantly longer than those of patients treated by endoscopy with TEVAR (7.00±2.74 days and 1.33±1.12 days, P<0.001 and P=0.001, respectively). Five cases had severe complications. CONCLUSION: Rational application of TEVAR can be a life-saving management for aortoesophageal foreign body injury, and jointed with endoscopy is safe and effective with a shorter length of ICU or total hospital stay.

Retrospective observational analysis of esophageal foreign bodies: a novel characterization based on shape.

This single-center retrospective study aims to investigate the clinical features of esophageal foreign bodies (EFBs) and determine the influence of EFB shapes on management and prognosis. A total of 427 patients aged 13 to 95 years with suspected EFB ingestion were enrolled between January 2013 and June 2018, 183 of whom were male. EFBs were divided into six shapes: pin (n = 161), sheet (n = 97), trident (n = 51), spindle (n = 66), irregular (n = 46), and sphere (n = 6). Spindle-shaped EFBs correlated with a significantly higher rate of perforation and severe complications (P < 0.001 and P = 0.021, respectively) than any other EFB shape, while sheet-shaped EFBs were linked to less severe complications (P = 0.006). The number of pressure points was provided to stratify the risk of poor prognosis for each shape. EFBs with only two pressure points (pin and spindle EFBs) required more advanced management strategies and were correlated with a higher number of patients suffering esophageal perforation (27.11%) and severe complications (12.44%) when compared with other shapes (χ2 = 11.149 and P = 0.001; χ2 = 5.901 and P = 0.015, respectively). Spindle shape was an independent risk factor for poor prognosis, and contributed a more clinical risk than the pin shape. In conclusion, clinical features, management, perforation rate, and severe complications differed based on EFB shape. The EFBs with two pressure points, especially the spindle-shaped EFBs, were more dangerous compared with those with more pressure points.

Bioinspired Shear-Flow-Driven Layer-by-Layer in Situ Self-Assembly.

Layer-by-layer (LbL) assembly is widely applied as a coating technique for the nanoscale control of architecture and related properties. However, its translational applications are limited by the time-consuming and laborious nature of the process. Inspired by the blood-clotting process, herein, we develop a shear-flow-driven LbL (SF-LbL) self-assembly approach that accelerates the adsorption rate of macromolecules by mechanically configuring the polymer chain via a coil-stretch transition, which effectively simplifies and speeds the diffusion-controlled assembly process. The structural characteristics and surface homogeneity of the SF-LbL films are improved, and diverse three-dimensional structures can be achieved. Functional SF-LbL-assembled surfaces for corneal modification are successfully fabricated, and the surface of wounded rat corneas and skin can be directly decorated in situ with SF-LbL nanofilms due to the advantages of this approach. Furthermore, in situ SF-LbL self-assembly has promise as a simple approach for the wound dressing for interventional therapeutics in the clinic, as illustrated by the successful in situ fabrication of drug-free layers consisting of chitosan and heparin on the dorsal skin of diabetic mice to rescue defective wound healing. This bioinspired self-assembly approach is expected to provide a robust and versatile platform with which to explore the surface engineering of nanofilms in science, engineering, and medicine.

Predictive value of the maximum serum creatinine value and growth rate in acute paraquat poisoning patients.

This retrospective and a single-center study evaluated the prognostic value of the maximum serum creatinine value (maxCr) and the maximum serum creatinine growth rate (Vmax) after paraquat (PQ) ingestion. One hundred and seventy-one patients with PQ poisoning were treated with a uniform protocol. Demographic variables, clinical manifestations, relevant laboratory data, maxCr and Vmax of all patients were recorded and calculated. The time after PQ ingestion of maxCr and Vmax were also recorded. Vmax and MaxCr exhibited statistically significant differences between the survivor (n = 53) and death (n = 118) groups. Vmax appeared earlier in the death group than the survivor group. Regard to the receiver operating characteristic (ROC) curve analysis, Vmax had an AUC of 0.861 (95% CI, 0.801-0.921) and the optimal cut-off value of 6.21 µmol/(L·h) (sensitivity, 76.3%; specificity, 81.1%). MaxCr had an area under the curve (AUC) of 0.821 (95% CI, 0.752-0.889) and the optimal cut-off value of 225.5 µmol/L (sensitivity, 82.2%; specificity, 67.9%). The comparison of the AUC in the two parameters showed no significant difference, but Vmax appeared earlier than maxCr. Based on binary logistic regression analysis, MaxCr and Vmax both showed strong predictive powers for evaluating the prognosis of acute PQ poisoning patients.