Protective effect of dexmedetomidine on lung injury during one-lung ventilation in elderly patients undergoing radical esophagectomy

Abstract This study investigated the protective effect of dexmedetomidine (Dex) on lung injury during one-lung ventilation (OLV) in elderly patients undergoing radical esophagectomy with remote ischemic preconditioning (RIPC). Fifty-four esophageal cancer patients undergoing radical esophagectomy were divided into control, RIPC and RIPC+Dex group. During the anesthesia and ventilation in surgery, the RIPC was performed in RIPC group, and the intravenous infusion of Dex based on RIPC was conducted in RIPC+Dex group. At the time immediately before OLV beginning (T1), 60 min of OLV (T2) and end of surgery (T3), the oxygenation index (OI) and respiratory index (RI) were recorded, and the serum superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) levels were determined. Results showed that, compared with RIPC group, in RIPC+Dex group the OI at T2 and T3 increased, the RI at T2 and T3 decreased, the serum SOD level at T3 increased, the serum MDA level at T3 decreased, the serum TNF-α and IL-6 levels at T2 and T3 decreased (all P < 0.05). In conclusion, for elderly patients undergoing radical esophagectomy with RIPC, Dex can effectively inhibit the oxidative stress and inflammatory response during OLV, thus alleviating the lung injury and reducing the postoperative complications.

Knockdown of VDAC1 alleviates the cognitive dysfunction secondary to sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE) is a serious and diffuse cerebral dysregulation with a high morbidity and mortality caused by sepsis. Mitophagy plays an important role in SAE, and microglial phagocytosis of apoptotic cells (efferocytosis) is the core of the brain regenerative response. Voltage dependent anion channel (VDAC1) is an important regulator of mitophagy. However, it remains unknown whether VDAC1 influences SAE progression by regulating mitophagy and efferocytosis. Herein, we explored the mechanism where knockdown of VDAC1 alleviated the cognitive dysfunction caused by sepsis-associated encephalopathy and further elucidated the underlying molecular mechanisms. SAE model in mice was established through caecal ligation and puncture (CLP). The increased mitophagy and decreased efferocytosis were observed by the transmission electron microscope (TEM) in the SAE model. Besides, immunoblot tests showed an interaction between autophagy and efferocytosis. Further behavior tests and TEM results indicated that knockdown of VDAC1 alleviated the cognitive dysfunction by decreasing the autophagy and increasing the efferocytosis in a PINK1/Parkin-dependent manner. Based on these results, we conclude that knockdown of VDAC1 alleviates the cognitive dysfunction in the CLP-induced SAE mouse model.

The long-term environmental risks from the aging of organochlorine pesticide lindane.

Although increased contact time (aging) of pesticides in the soil decreases their bioavailability, this does not mean that the bound residues formed during the aging process pose fewer risk to the soil environment. Here the earthworm Eisenia fetida was exposed to organochlorine pesticide lindane in soil under different durations of lindane aging and exposure. The results of de novo RNA sequencing followed by molecular and biochemical validations demonstrated the aged lindane showed a different tendency to disrupt acetylcholine (ACh) transmission with the effects of fresh lindane to gamma-aminobutyric acid. Using own-developed earthworm activity test, we confirmed aged lindane prompted earthworms to exclusively exhibit a significant hypoactivity in locomotion, which could be explained by the inhibition of Ach system. This study suggested that the toxicity of pesticides would not depend solely on their free state components, and the awareness of long-term environmental risks from the bound states needs to be raised.

A sensitive optical-based test method for the locomotor activity of earthworms.

The outdated test methodologies for terrestrial animals have limited the progress of soil ecotoxicology to some extent. To improve the behavioral testing of earthworms, a terrestrial model animal, a sensitive optical-based method for detecting locomotor activity was established. The method measured the fine quantified position offsets of each earthworm in place of a conventional overall response rate, which provided the feasibility for accurate analyses and comparisons. By setting appropriate thresholds, the time proportions of medium and burst states (mid-burdur%) could be an optimized endpoint with an ideal balance in output stability and sensitivity. In addition, we chose the head-end, which is the most flexible part of the earthworm, other than whole body to further elevate the sensitivity in indicating the changed traits. Using octopamine, serotonin, and a serial-dose of lindane exposure, the practice credibility of the test method was validated. Our developed locomotor test method overcame the innate characteristics of the earthworm, and was expected to provide a powerful phenotypic tool for ecological and ecotoxicological studies using earthworms and similar invertebrates.

Bioaccumulation, distribution and elimination of lindane in Eisenia foetida: The aging effect.

Soil aging will influence the chemical speciation of pesticides, thus affecting the uptake route to be bioavailable to the organism. So far, studies on the possible effects of the uptake route on the distribution and elimination of pesticides in the organism that also considers effects of aging are limited. In our study, Eisenia fetida was exposed to 4.5 mg kg-1 lindane aging for 0, 30 and 180 d, and the accumulation, distribution and elimination of lindane in the earthworms were analyzed. The results showed that the 6 h Tenax-extracted fraction exhibited a good linear correlation with the lindane accumulated in the earthworms. With aging time increasing, the bioaccumulation of lindane decreased and the accumulative balance was more easily reached in the earthworms. Lindane distributions were found in the whole earthworm and the proportions of lindane content at sub-organism level and the mass distribution of each fraction were similar for 0 d and 180 d aged groups. The foregut accumulated the highest content of lindane (20%) relative to its low mass distribution proportion (10%). The elimination rate of lindane in the earthworms decreased with aging time extending. Our conclusion was that the 6 h Tenax extraction could be used to assess the bioavailability of aging lindane. Although soil aging decreased the bioavailability of lindane, the soil-bound lindane entered the earthworm through dietary route would take longer to depurate from the organisms than free lindane, which implied the potential ecological risk of bound pesticide residues.

Seasonal variation in air particulate matter (PM10) exposure-induced ischemia-like injuries in the rat brain.

Epidemiological studies imply a significantly positive association between particulate matter (PM) level and ischemic stroke hospitalization. However, considering that PM10 is highly heterogeneous and varies with season within the same location, existing experimental evidence remained low. In the present study, we first treated Wistar rats with PM10 samples collected from different seasons in Taiyuan, a typically coal-burning city of China, and determined ischemia-related markers in the cortex. The results indicated that PM10 exposure caused endothelial dysfunction, inflammatory response, and neuro-functional impairment similar to that of cerebral ischemia with season-dependent properties, and the winter sample presented the most obvious injuries. Then, we detected the chemical composition of PM10 samples followed by analysis of their correlation with the above biomarkers and found that winter PM10, characterized by higher polycyclic aromatic hydrocarbons (PAHs) and carbon load, played the major role in causing brain ischemia-like injuries among different season samples. Furthermore, by setting up an ischemic neuron model in vitro, we confirmed that winter PM10 presented the most serious aggravation on ischemia-produced injury outcome. This study provides experimental evidence for clarifying the association between season-dependent PM10 pollution in the atmospheric environment and an increased risk of ischemia-like injuries.