Standardization of Methods for Early Diagnosis and On-Site Treatment of High-Altitude Pulmonary Edema

High-altitude pulmonary edema (HAPE) is a life-threatening disease of high altitude that often affects nonacclimatized apparently healthy individuals who rapidly ascend to high altitude. Early detection, early diagnosis, and early treatment are essential to maintain the safety of people who ascend to high altitude, such as construction workers and tourists. In this paper, I discuss various methods and criteria that can be used for the early diagnosis and prediction of HAPE. I also discuss the preventive strategies and options for on-site treatment. My objective is to improve the understanding of HAPE and to highlight the need for prevention, early diagnosis, and early treatment of HAPE to improve the safety of individuals ascending to high altitude

Mouse Model Established by Early Renal Transplantation After Skin Allograft Sensitization Mimics Clinical Antibody-Mediated Rejection

Antibody-mediated rejection (AMR) is the main barrier to renal graft survival, and mouse renal AMR models are important to study this process. Current mouse models are established by priming the recipient to donor skin for over 7 days before kidney transplantation. The robustness of AMR in these cases is too strong to mimic clinical AMR and it is unclear why altering the priming times ranging from 7 to 91 days fails to reduce the AMR potency in these models. In the present study, we found that the donor-recipient combination and skin graft size were determinants of donor-specific antibody (DSA) development patterns after skin transplantation. DSA-IgG was sustained for over 100 days after skin challenge, accounting for an identical AMR robustness upon different skin priming times over 7 days. However, decreasing the skin priming time within 7 days attenuated the robustness of subsequent renal allograft AMR in C3H to Balb/c mice. Four-day skin priming guaranteed that recipients develop acute renal AMR mixed with a high ratio of graft-infiltrating macrophages, renal grafts survived for a mean of 6.4 ± 2.1 days, characterized by typical AMR histological changes, such as glomerulitis, peritubular capillary (PTC) dilation, and capillaritis, deposition of IgG and C3d in PTCs, but less prevalence of microthrombus, whereas the cellular rejection histological change of tubulitis was absent to mild. With this scheme, we also found that the renal AMR model can be developed using common mouse strains such as C57BL/6 and Balb/c, with mean prolonged renal graft survival times of 14.4 ± 5.0 days. Finally, we proved that donor-matched skin challenge after kidney transplantation did not strongly affect DSA development and kidney graft outcome. These findings may facilitate an understanding and establishment of mouse renal allograft AMR models and promote AMR-associated studies

A Randomly-Controlled Study on the Cardiac Function at the Early Stage of Return to the Plains after Short-Term Exposure to High Altitude

High altitude acclimatization and adaptation mechanisms have been well clarified, however, high altitude de-adaptation mechanism remains unclear. In this study, we conducted a controlled study on cardiac functions in 96 healthy young male who rapidly entered the high altitude (3700 m) and returned to the plains (1500 m) after 50 days. Ninety eight healthy male who remained at low altitude were recruited as control group. The mean pulmonary arterial pressure (mPAP), left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), cardiac function index (Tei index) were tested. Levels of serum creatine kinase isoform MB (CK-MB), lactate dehydrogenase isoenzyme-1 (LDH-1), endothelin-1 (ET-1), nitrogen oxide (NO), serum hypoxia-inducible factor-1α (HIF-1α), 8-iso-prostaglandin F2α (8-iso PGF2α), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured at an altitude of 3700 m and 1500 m respectively. The results showed that after short-term exposure to high altitude mPAP and Tei index increased significantly, while LVEF and LVFS decreased significantly. These changes were positively correlated with altitude. On the 15th day after the subjects returned to low altitude, mPAP, LVEF and LVFS levels returned to the same level as those of the control subjects, but the Tei index in the returned subjects was still significantly higher than that in the control subjects (P<0.01). We also found that changes in Tei index was positively correlated with mPAP, ET-1, HIF-1α and 8-iso PGF2α levels, and negatively correlated with the level of NO, LVEF, LVFS, CK-MB and LDH-1. These findings suggest that cardiac function de-adapts when returning to the plains after short-term exposure to high altitude and the function recovery takes a relatively long time

Role of TLR4/NF-κB in damage to intestinal mucosa barrier function and bacterial translocation in rats exposed to hypoxia.

The role of Toll-like receptor 4 (TLR4)/nuclear factor-kappa-B (NF-κB) in intestinal mucosal barrier damage and bacterial translocation under hypoxic exposure is unclear. Here, we investigated their role using an acute hypobaric hypoxia model. Adult Sprague-Dawley rats were divided into control (C), hypoxia (H), hypoxia+NF-κB inhibitor pyrrolidinedithiocarbamic acid (PDTC) (100 mg. kg) (HP), hypoxia+0.5 mg/kg lipopolysaccharide (HPL), and hypoxia+PDTC+LPS (HPL) group. Except control group, other four groups were placed in a hypobaric chamber set at 7000 m. Samples were collected at 72 h after pressure reduction. Damage in ultrastructure of the intestinal tract was examined by transmission electron microscopy and bacterial translocation was detected by cultivation. Kinetic turbidimetric assay was used to measure the serum LPS.ELISA was performed to detect TNF-α and IL-6 serum concentrations. Fluorescent quantitative RT-PCR was used to measure TLR4 mRNA levels was measured using quantitative RT-PCR and protein of NF-κB p65 was measured by western blotting. Different degrees of intestinal mucosa damage were observed in groups H and HL. The damage was significantly alleviated after blockage of the TLR4/NF-κB signaling pathway. PDTC- treatment also reversed hyoxia- and LPS-induced bacterial translocation rate and increased serum levels of LPS, TNF-α, and IL-6. TLR4 mRNA levels and NF-κB p65 expression were consistent with the serum factor results. This study suggested that TLR4 and NF-κB expression increased in rat intestinal tissues after acute hypoxia exposure. PDTC-treatment reversed TLR4 and NF-κB upregulation and alleviated damage to the intestinal tract and bacterial translocation. Thus, the TLR4/NF-κB signaling pathway may be critical to the mechanism underlying hypoxia-induced damage to intestinal barrier function and bacterial translocation

Modeling of interfacial and bulk charge transfer in dye-sensitized solar cells

A simple, first-principles mathematical model has been developed to analyze the effect of interfacial and bulk charge transfer on the power output characteristics of dye-sensitized solar cells (DSSCs). Under steady state operating conditions, the Butler-Volmer equation and Schottky barrier model were applied to evaluate the voltage loss at counter electrode/electrolyte and TiO2/TCO interfaces, respectively. Experimental data acquired from typical DSSCs tested in our laboratory have been used to validate the theoretical J–V characteristics predicted by the present model. Compared to the conventional diffusion model, the present model fitted the experimental J–V curve more accurately at high voltages (0.65–0.8 V). Parametric studies were conducted to analyze the effect of series resistance, shunt resistance, interfacial overpotential, as well as difference between the conduction band and formal redox potentials on DSSCs’ performance. Simulated results show that a “lower-limit” of shunt resistance (103 Ωcm2) is necessary to guarantee a maximized efficiency. The model predicts a linear relationship between open circuit voltage (Voc) and photoanode temperature (T) with a slope of −1 mV/°C, which is close to the experimental data reported in literature. Additionally, it is observed that a small value of overpotential (2.2 mV) occurs at the short-circuit condition (Jsc = 10.5 mA/cm2), which is in a close agreement with Volmer-Butler equation. This observation suggests that, compared to the maximum attainable voltage (700 mV), the overpotential values are small and can be neglected for platinum catalyst based DSSCs

Changes in the ultrastructure of rat intestinal microvilli and interstitial space.

<p><b>A</b> In the group C, La³⁺ particles were distributed in the lumen of the small intestine. The number and structure of microvilli were normal. No La³⁺ particles were found in the intercellular space. TEM, ×15,000. <b>B</b> In the H group, the TJs between epithelial cells were expanded. La³⁺ particles were observed in the intercellular space and TJs. TEM, ×15,000. <b>C</b> In the H group, atrophy and the sloughing of some small intestinal microvilli were observed. Swelling of mitochondria, endoplasmic reticulum, part of the regional organizations is completely dissolved.. TEM, ×8900. <b>D</b> In the HP group, La³⁺ particles were observed in the lumen of the intestine. The number of epithelial microvilli was reduced, some microvilli damage,organelle ultrastructure basic normal. No La³⁺ sediment was observed in the intercellular space. TEM, ×15,000. <b>E</b> In the HLgroup, Intestinal epithelial cell necrosis, microvilli destruction collapse, organelle dissolution, a large number of La³⁺ particles into the tissue space and cytoplasm. TEM, ×15,000. <b>F</b> In the HPL group, microvilli structure is normal, a small amount of of La³⁺ particles attached to the surface of microvilli, and no La³⁺ particles were found in organizational gap and TJs.TEM, ×15,000.</p

WB detection of protein expressions of NF-κB p65 and occluding.

<p><b>A</b> WB result for NF-κB p65 and occludin. <b>B</b> Quantification for expression of NF-κB p65 protein. <b>C</b> Quantification for expression of occludin protein. ^a<i>P</i><0.01 compared to group C; ^b<i>P</i><0.01 compared to group H; ^c<i>P</i><0.01 compared to group HL.</p

Rate of bacterial translocation in rats from different groups.

<p>Note:</p>a<p><i>P</i><0.01 compared to group C;</p>b<p><i>P</i><0.01 compared to group H;</p>c<p><i>P</i><0.01 compared to group HL.</p