Autophagy-Lysosome Pathway in Renal Tubular Epithelial Cells Is Disrupted by Advanced Glycation End Products in Diabetic Nephropathy.

It has been suggested that autophagy protects renal tubular epithelial cells (TECs) from injury in diabetic nephropathy (DN). However, the manner in which the autophagy-lysosome pathway is changed in this state remains unclear. In this study of DN, we investigated the autophagic activity and lysosomal alterations in vivo and in vitro. We found that autophagic vacuoles and SQSTM1-positive proteins accumulated in TECs from patients with DN and in human renal tubular epithelial cell line (HK-2 cells) treated with advanced glycation end products (AGEs), the important factors that involved in the pathogenesis of DN. In HK-2 cells, exposure to AGEs caused a significant increase in autophagosomes but a marked decrease in autolysosomes, and the lysosomal turnover of LC3-II was not observed, although LC3-II puncta were co-localized with the irregular lysosomal-associated membrane protein1 granules after AGEs treatment. Furthermore, lysosomal membrane permeabilization was triggered by AGEs, which likely resulted in a decrease in the enzymatic activities of cathepsin B and cathepsin L, the defective acidification of lysosomes, and suppression of the lysosomal degradation of DQ-ovalbumin. Oxidative stress evoked by AGEs-receptor for AGE interaction likely played an important role in the lysosomal dysfunction. Additionally, ubiquitinated proteins were co-localized with SQSTM1-positive puncta and accumulated in HK-2 cells after exposure to AGEs, indicating blocked degradation of SQSTM1-positive and ubiquitinated aggregates. Taken together, the results show that lysosomal membrane permeabilization and lysosomal dysfunction are triggered by AGEs, which induce autophagic inactivation in TECs from patients with DN. Disruption of the autophagy-lysosome pathway should be focused when studying the mechanisms underlying DN.

Explaining the stability of cooperation in agricultural industry chains based on the institutional theory: Multiple mediating effects of perceived value and trust.

Introduction: Due to the superposition of multiple complex socioeconomic environments and the complexity and uncertainty of the agricultural industry chain itself, the agricultural industry chain has become unstable, jeopardizing its long-term sustainability. Methods: The purpose of this study is to construct and validate a stability mechanism model of cooperative relationships within agricultural industry chains based on the institutional theory. The questionnaire survey method was used for empirical analysis. Results: The results show that imitative pressure, mandatory pressure, and normative pressure have significant positive effects on the stability of cooperative relationships in agricultural industrial chains. Besides, perceived benefits, perceived risks, and trust play composite multiple mediating roles between imitative pressure and cooperation stability, and between normative pressure and cooperation stability in agricultural industrial chains. Perceived benefits and trust play partial mediating roles in the stability of cooperative relationships between mandatory pressure and agricultural industrial chains. Discussion: This study is conducive to further understanding the cooperative psychology of agricultural industry chain operators. And this research can provide a reference for managers to take targeted measures to deal with the instability in the development of agricultural industry chains.

[The effects of positive end-expiratory pressure targeting optimal oxygenation on local gas distribution and inflammation in dogs with acute respiratory distress syndrome].

OBJECTIVE: To evaluate the effects of positive end-expiratory pressure (PEEP) targeting optimal oxygenation on local gas distribution and inflammation in dogs with acute respiratory distress syndrome (ARDS). METHODS: ARDS was induced by saline alveoli-lavage and oleic acid intravenous. The animals were mechanical ventilated 4 h at optimal PEEP titrated by oxygenation. Computed tomography (CT) scans were performed before and after induction of ARDS and at the end the study. NF-κB was measured by electrophoretic mobility shift assay (EMSA), IL-6 and IL-10 were assessed by ELISA. Myeloperoxidase (MPO) and malondialdehyde (MDA) were measured. Pathological changes were examined under optical microscope. RESULTS: (1) Compared to baseline, total lung volumes decreased and nonaerated areas increased significantly after the induction of ARDS in both groups (P < 0.05). Compared with ARDS models, PEEP titrated to achieve optimal oxygenation resulted in greater lung recruitment but was accompanied with hyperinflation, hyperinflation occurred in non-dependent lung. Compared with oleic acid-injured ARDS, the changing of hyperinflated lung areas was increased markedly in saline lavage-injured ARDS (P < 0.05). (2) Compared with right lung ventral lower lobe, lung injury score was lower in right lung upper lobe. Histological injury in right lung dorsal lower lobe was severer than that in right lung upper lobe and right lung ventral lower lobe. NF-κB activation of right lung dorsal lower lobe was markedly higher than right lung upper lobe (P < 0.05). MPO and MDA were much higher with right lung dorsal lower lobe than right lung upper lobe and right lung ventral lower lobe (P < 0.05). Compared with right lung upper lobe and right lung ventral lower lobe, IL-6 and IL-10 increased markedly in right lung dorsal lower lobe (P < 0.05). CONCLUSIONS: Alveolar hyperinflation and aggravated lung injury in non-dependent region were occurred at PEEP targeting optimal oxygenation. Hyperinflation was more common in saline lavage-injured ARDS.

[Effects of the treatment with different fluids on alveolar epithelium barrier in rats with acute lung injury].

OBJECTIVE: To observe the effects of different fluids on alveolar epithelium barrier in rats with acute lung injury (ALI). METHODS: Thirty-six Sprague-Dawley (SD) rats were randomly assigned into six groups with 6 rats in each group. ALI was induced by intravenous injection of lipopolysaccharide(LPS). Rats in all treatment groups were given different fluids and sacrificed after 4 hours. Evans blue dye (EBD) was injected via the femoral vein 30 minutes before death. Tracheobronchial tree was washed with normal saline (NS) after death, and broncho-alveolar lavage fluid (BALF) was collected. Leakage of EBD from blood into BALF (alveolar epithelial permeability) and wet/dry (W/D) ratio were measured. The mRNA expression of surfactant protein-C (SP-C) was assessed by reverse transcription-polymerase chain reaction (RT-PCR). Alveolar epithelium apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL). Lung injury was evaluated by Smith lung injury score. RESULTS: (1) Lung injury scores in LPS and NS groups were significantly higher than in control group (both P < 0.05). Compared with NS group, lung injury scores were significantly lower in 5% albumin (ALB) and 6% hydroxyethyl starch 130/0.4 (HES) groups (both P < 0.05), and there was no significant difference in 4% succinylated gelatin (GEL) group (P > 0.05). No significant difference was found among the latter three groups. (2) W/D ratio in LPS and NS groups were significantly higher than that in control group (both P < 0.05). Compared with NS group, W/D ratios were lower in ALB, HES and GEL groups (all P < 0.05). But it showed no significant difference among the latter three groups. (3) Alveolar epithelial permeability in LPS and NS groups were remarkably higher than that in control group (both P < 0.05). Compared with NS group, the alveolar epithelial permeability were significantly lower in ALB, HES and GEL groups (all P < 0.05). The alveolar epithelial permeability in the latter two groups were significant lower than that in ALB group (both P < 0.05) but higher than that of control group. (4) The SP-C mRNA expression in LPS, NS, ALB and GEL groups were lower than that in control and HES groups (all P < 0.05), but there was no difference between control and HES groups (P > 0.05). (5) Apoptosis index (AI) of alveolar epithelial cell in all the treatment groups were significantly higher than that in control group (all P < 0.05). Compared with NS group, AI were noticeably lower in ALB and HES groups (both P < 0.05). CONCLUSION: Compared with NS, colloid can probably improve the alveolar epithelial permeability and protect the barrier function.

Effects of Hand Exercise on Eating Action in Patients With Alzheimer's Disease.

We aim to investigate whether a popular hand exercise could be used to improve the action of eating in patients with Alzheimer's disease (AD). A 6-month intervention was conducted in 60 patients with AD who live in a nursing home. They were divided into hand exercise and control groups. Patients of the control group maintained their daily routine. The improvement of Edinburgh Feeding Evaluation in Dementia scale in hand exercise group was significantly greater than in the control group ( P = .003). Significant differences in time of autonomous eating and time of simulated eating between patients in the hand exercise and control groups ( P < .05) were noted. The improvements in accuracy of eating action and coordination of eating action from baseline were significant in hand exercise group compared to the control group ( P = .020 and .014, respectively). Hand exercise is a safe and effective intervention to improve the feeding and eating of people with AD.

Managing congestion at visitor hotspots using park-level use level data: Case study of a Chinese World Heritage Site.

Tourist congestion at hot spots has been a major management concern for UNESCO World Heritage Sites and other iconic protected areas. A growing number of heritage sites employ technologies, such as cameras and electronic ticket-checking systems, to monitor user levels, but data collected by these monitoring technologies are often under-utilized. In this study, we illustrated how to integrate data from hot spots by camera-captured monitoring and entrance counts to manage use levels at a World Heritage Site in Southeastern China. 6,930 photos of a congestion hotspot (scenic outlook on a trail) were collected within the park at a 10-minute interval over 105 days from January to November 2017. The entrance counts were used to predict daily average and maximum use level at the hotspots. Results showed that the average use level at the congestion hotspot did not exceed the use limit mandated by the park administration agency. However, from 9:20 am to 12:00 pm, the use level at hotspots exceeded visitor preferred use level. Visitor use level was significantly higher at the hotspot during a major Chinese "Golden Week". The daily entrance counts significantly predicted the average and maximum use level at the hotspot. Based on our findings, park managers can achieve the management goals by permitting the corresponding number of visitors passing the entrances. The gap manifested the complexities in visitor capacity management at high-use World Heritage Sites and other protected areas and calls for innovative monitoring and management strategies.

[Effects of recruitment maneuvers in prone position for pulmonary or extra-pulmonary acute respiratory distress syndrome on hemodynamics in dog].

OBJECTIVE: To evaluate the effect of recruitment maneuvers in prone positioning on hemodynamic in dogs with acute respiratory distress syndrome (ARDS) of pulmonary or extra pulmonary origin. METHODS: Forty-eight mongrel dogs were randomly divided into 8 groups with six dogs in each group. Hydrochloric acid was instilled into trachea to reproduce pulmonary ARDS (ARDSp) and oleic acid was intravenously injected to produce extra-pulmonary ARDS (ARDSe). ARDSp and ARDSe dogs were divided into conventional mechanical ventilation group (group A), prone-position ventilation group (group B), sustained inflation (SI) group (group C) and prone-position ventilation + SI group (group D) respectively. Hemodynamic parameters were monitored before injury and 0, 2 and 5 hours after ARDS was reproduced. RESULTS: (1) In group A and group C, central venous pressure (CVP) increased significantly at 5 hours after ARDSp. Five hours after the establishment of ARDSp, pulmonary arterial wedge pressure (PAWP) increased in group C and group D. Mean pulmonary arterial pressure (MPAP) increased remarkably in group A, group C and group D at 2 hours and 5 hours after onset of ARDSp. In group C, intrathoracic blood volume index (ITBI) decreased at 5 hours after the onset of ARDSp. In all the four groups, extravascular lung water index (EVLWI) increased sharply at 0, 2 and 5 hours after onset of ARDSp. In group B and group C, cardiac index (CI) decreased to a greater extent at 2 and 5 hours after onset of ARDSp. CI decreased at 2 hours after onset of ARDSp in group D with statistically significant difference at different time points (all P<0.05). (2) In all four groups, EVLWI increased sharply at 0, 2 and 5 hours after onset of ARDSe. In ARDSe model, there was no significant difference in other hemodynamic parameters between groups (all P>0.05). CONCLUSION: There are less influence on hemodynamics when SI is performed in prone position, and it is even more significantly so in ARDS dogs.

[Angiotensin II type 2 receptor expression and its modulation in angiotensin II induced acute lung injury in rat].

OBJECTIVE: To study the effect of angiotensin II (Ang II) and losartan, which is an angiotensin II type 1 receptor (AT1R) antagonist, on expression of AT2R in rat lung and the relationship between AT2R with acute lung injury (ALI). METHODS: Twenty-four Sprague-Dawley (SD) rats were randomly divided into normal group, Ang II group, Ang II + losartan group and losartan group, with 6 rats in each group. Normal group and Ang II group were treated with continuous subcutaneous injection of normal saline (NS, 1 microg.kg(-1).min(-1)) or Ang II (1 microg.kg(-1).min(-1)) for 72 hours respectively. Ang II + losartan group was gavaged with losartan (10 mg.kg(-1) .d(-1)) 24 hours before and during the 72 hours' continuous subcutaneous injection of Ang II for a duration of 4 days. In losartan group rats were gavaged with losartan (10 mg.kg(-1).d(-1)) for 4 days only. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were employed to measure AT2R mRNA and protein. The pathology of the rat pulmonary was scored. RESULTS: Smith's score of pathology in Ang II group [(3.33+/-1.14) scores] was significantly higher than that of the normal group [(0.73+/-0.09) scores], while it was significantly lower in Ang II + losartan group [(1.98+/-0.30) scores] than that of Ang II group. Smith's score of pathology in losartan group was [(0.95+/-0.20) scores]. The differences among four groups showed significant statistical difference (P<0.05 or P<0.01). AT2R mRNA in Ang II group [(47.90+/-9.88)%] was significantly lower than that of normal group [(86.33+/-5.90)%], while it was significantly higher in Ang II + losartan group [(90.63+/-19.66)%] than Ang II group . AT2R mRNA of losartan group was (68.65+/-4.88)% . The differences among four groups had significant statistical difference (P<0.05 or P<0.01). While on protein level showed no statistically significant difference among the four groups. The values of AT2R were (78.80+/- 41.26)%, (68.98+/-23.93)%, (68.13+/-23.23)% and (70.15+/-17.16)%, respectively. CONCLUSION: Ang II could induce ALI and downregulate AT2R mRNA expression in the lung of ALI rats, whereas losartan acts as a positive regulator. AT2R seems to present lung protection in ALI.

[Clinical Trial of Electroacupuncture Treatment for Relieving Stress Responses in Patients Undergoing Gastrointestinal Surgery].

OBJECTIVE: To observe the therapeutic effect of electroacupuncture (EA) at Zusanli (ST 36) and Neiguan (PC 6) on stress responses of patients undergoing gastrointestinal surgery. METHODS: A total of 40 patients undergoing gastrointestinal surgery were randomized into conventional treatment group (control) and EA group (n＝20 in each group). Patients of the EA group received conventional treatment (pre- and post-surgical fasting, measures for gastrointestinal decompression, parenteral nutrition support, and patient controlled analgesia pump, etc.) and EA stimulation (2 Hz, 30 min) of bilateral ST 36 and PC 6 (twice after surgery, at an interval of 6 h), and patients of the control group received conventional treatment only. The visual analogue scale (VAS) score was used to assess the patients' pain severity and the blood glucose levels were detected once every 4－6 h within 24 h after operation. Serum cortisol (Cort) and adrenocorticotropic hormone (ACTH) levels were detected by chemiluminescence method, and serum D-lactic acid level (for assessing gastrointestinal mucosal injury) was assayed by ELISA. RESULTS: After the treatment, the levels of serum Cort, ACTH, D-lactate acid and the highest blood glucose were significantly lower in the EA group than those in the control group (P<0.05, P<0.01), suggesting a reduction of stress reactions after EA. But no significant difference was found between the control and EA groups in the VAS score (P>0.05). CONCLUSION: EA at ST 36 and PC 6 can alleviate stress responses and reduce intestinal mucosal damage in patients undergoing gastrointestinal surgery.