Pulmonary fibrosis is the primary reason for mortality in patients with paraquat (PQ) poisoning. Our previous study demonstrated that epithelial-mesenchymal transition (EMT) had a role in PQ-induced pulmonary fibrosis. However, the role of endoplasmic reticulum (ER) stress in PQ-induced EMT remains clear. The present study aimed to determine the role of ER stress in EMT in PQ-induced pulmonary fibrosis. A549 and RLE-6TN cells were incubated with LY294002 (a PI3K inhibitor) or transfected with protein kinase RNA-like ER kinase (PERK) small interfering RNA (si) for 24 h prior to being exposed to PQ. Next, the expression levels of ER stress-related proteins, PI3K/AKT/GSK-3 beta signaling pathway-related proteins and EMT-related markers were analyzed by performing western blotting, reverse transcription-quantitative PCR and immunofluorescence assays. The results of the present study revealed that the protein expression levels of PERK, phosphorylated (p)-PERK, p-eukaryotic initiation factor 2 (eIF2)alpha were significantly upregulated in the PQ group, whereas p-PI3K, p-AKT and p-GSK-3 beta were significantly upregulated in the sicontrol + PQ group compared with the sicontrol group. In vitro, following transfection with siPERK or treatment with the PI3K inhibitor, the protein expression levels of E-cadherin (an epithelial marker) were upregulated, whereas the protein expression levels of alpha-SMA (a mesenchymal marker) were downregulated. Immunofluorescence analysis revealed that the levels of E-cadherin were markedly upregulated, whereas the levels of alpha-SMA were notably downregulated following transfection with siPERK compared with the sicontrol group. The results of wound healing assay demonstrated that cell migration in the siPERK + PQ group was markedly decreased compared with the sicontrol + PQ group. These indicated that PQ-induced EMT was suppressed after silencing PERK. The expression levels of p-GSK-3 beta, p-AKT and p-PI3K were also markedly downregulated in the siPERK + PQ group compared with the sicontrol + PQ group. In conclusion, the findings of the present study suggested that ER stress may promote EMT through the PERK signaling pathway in PQ-induced pulmonary fibrosis. Thus, ER stress may represent a potential therapeutic target for PQ-induced pulmonary fibrosis.

Hyperoxic acute lung injury (HALI) is caused by prolonged exposure to high oxygen partial pressure. This study was undertaken to investigate the protective effects of oridonin on HALI in a mouse model. Mice were randomly divided into three groups: the control group, HALI group and oridonin (ORI) group. HALI was induced by exposing mice to pure oxygen at 2.5 atmospheres absolute (ATA) for six hours in the HALI and ORI groups. In the ORI group, mice were intraperitoneally injected with ORI at 10 mg/kg twice daily after hyperoxic exposure. Animals were sacrificed 24 hours after the hyperoxia exposure, followed by bronchoalveolar lavage fluid (BALF). Lungs were then collected. Each lung was processed for HE staining and detection of wet-to-dry weight ratio. The lactate dehydrogenase (LDH) activity and protein content of BALF were determined, and the contents of malonaldehyde (MDA), glutathione (GSH), tumor necrosis factor alpha (TNF-?) and interleukin-10 (IL-10) in the lung were measured. Our results showed prolonged exposure to hyperoxia significantly damaged the lung, caused lung edema, increased MDA and TNF-?, and reduced GSH and IL-10 in the lung. However, post-exposure treatment with oridonin was able to improve lung pathology, attenuate lung edema, reduce MDA and TNF-?, and increase GSH and IL-10 in the lung. These findings suggest that oridonin can protect the lung against hyperoxia-induced injury in mice.

随着潜水技术和潜水装备的发展,潜水现场对潜水医生的需求也不断增加,而现实的情况是目前的潜水医生数量不能满足当前的潜水作业需求.因此,潜水医学技士(DMT)应运而生.DMT指接受过潜水医学和现场医疗急救技能培训,具备在潜水现场,包括水下或加压舱内对伤病潜水员实施医疗救护的潜水员.但是,DMT的职责和任务与潜水医生存在明显的差异,这一点也体现在DMT的培训上.该文对DMT的分级培训、参训人员条件、培训的内容和考核要求提出几点看法旨在提升我国DMT培训人员的素质,形成具有鲜明特色的DMT培训模式,早日获得国际同行的认可.

Current study findings concerning changes in the renin-angiotensin system (RAS) in cases of hyperoxic acute lung injury (HALI) have shown conflicting results. This study aimed to detect the angiotensin II (Ang II) and angiotensin-converting enzyme (ACE) in a rat HALI model. Healthy male Sprague-Dawley rats were randomly assigned into three groups: the control group, HALI group and hyperbaric oxygen preconditioning (HBO2-PC) group. HALI was induced by exposure to pure oxygen at 250 kPa for six hours. In the HBO2-PC group, rats were exposed to oxygen at 250 kPa for 60 minutes twice daily for two consecutive days; HALI was induced at 24 hours after the last oxygen exposure. After HALI, the lung, spleen and liver were harvested for HE staining and pathological examination. At one hour and 18 hours after HALI, the blood, liver, lung and spleen were collected for the detection of Ang II and ACE contents by enzyme-linked immunosorbent assay. Pathological examination showed the lung was significantly damaged and characteristics of HALI were observed, but there were no significant pathological changes in the liver and spleen. After HALI, Ang II and ACE contents of different tissues increased progressively over time, but HBO2-PC group showed reductions in the Ang II and ACE contents to a certain extent, especially at 18 hours after injury. These findings suggest prolonged hyperoxia exposure may activate the RAS, which may be associated with the pathogenesis of HALI. HBO2-PC has a limited capability to inhibit RAS activation.

OBJECTIVE:To explore the possible effects of rapid decompression on the activity and function of vascular endothelial cells in vitro.METHODS:Human umbilical vein endothelial cell (HUVEC) cultures were exposed at 7 atmospheres absolute (atm abs) air for two hours before decompression. Two decompression profiles were used at the rate of 30 atm abs min-1 (rapid decompression) or 1 atm abs min-1 (normal decompression). Three hours after decompression, cell activity was detected by cell counting kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) activity assay; cell permeability was measured by electrical resistance determinations. Twelve hours after decompression, cell apoptosis was detected by flow cytometry with Annexin V FITC/PI double staining.RESULTS:There was no significant statistical difference between rapid and normal decompression groups in all the determined parameters (P=0.59, 0.87, 0.86 and 0.81, respectively).CONCLUSIONS:HUVECs endure rapid decompression well from 7 atm abs at the rate of 30 atm abs min-1, or the current determinations are not sensitive enough to reveal the possible injuries. Further research with more sensitive indexes is warranted to reveal the possible effects and mechanisms.

Hyperoxic acute lung injury (HALI) refers to the damage to the lungs secondary to exposure to elevated oxygen partial pressure. HALI has been a concern in clinical practice with the development of deep diving and the use of normobaric as well as hyperbaric oxygen in clinical practice. Although the pathogenesis of HALI has been extensively studied, the findings are still controversial. Nitric oxide (NO) is an intercellular messenger and has been considered as a signaling molecule involved in many physiological and pathological processes. Although the role of NO in the occurrence and development of pulmonary diseases including HALI has been extensively studied, the findings on the role of NO in HALI are conflicting. Moreover, inhalation of NO has been approved as a therapeutic strategy for several diseases. In this paper, we briefly summarize the role of NO in the pathogenesis of HALI and the therapeutic potential of inhaled NO in HALI.

Decompression sickness (DCS) is a specific diving injury which sometimes may be life-threatening. Previous studies suggested that simvastatin (SIM) can protect against pathological inflammation and tissue damage. This study aimed to investigate whether SIM pretreatment could exert its beneficial effects on DCS. SIM was administered orally to adult male Sprague-Dawley rats for two weeks (2 mg/kg/day), then rats were subjected to a simulated dive at 700 kPa air pressure for 100 minutes before rapid decompression. After 30 minutes of symptom observation, lung tissue and blood samples were collected for further analysis. Compared to the vehicle-control, SIM pretreatment significantly decreased the incidence of DCS and ameliorated all parameters of pulmonary injuries, including lung dry/wet weight ratio, bronchoalveolar lavage fluid protein concentration, lung tissue malondialdehyde level and morphology. Moreover, SIM pretreatment abolished increases in systemic and pulmonary inflammation by reducing tumor necrosis factor-α levels in blood plasma and lung tissue. The results indicate that SIM may offer a novel pharmacological protection against injuries in DCS rats by inhibiting inflammatory responses. Further study is needed to understand the exact mechanisms.

Ethyl pyruvate (EP) is a simple aliphatic ester of the metabolic intermediate pyruvate that has been demonstrated to be a potent anti-inflammatory agent in a variety of in vivo and in vitro model systems. However, the protective effects and mechanisms underlying the actions of EP against endothelial cell (EC) inflammatory injury are not fully understood. Previous studies have confirmed that endoplasmic reticulum stress (ERS) plays an important role in regulating the pathological process of EC inflammation. In this study, our aim was to explore the effects of EP on tumor necrosis factor-α (TNF-α)-induced inflammatory injury in human umbilical vein endothelial cells (HUVECs) and to explore the role of ERS in this process. TNF-α treatment not only significantly increased the adhesion of monocytes to HUVECs and inflammatory cytokine (sICAM1, sE-selectin, MCP-1 and IL-8) production in cell culture supernatants but it also increased ICAM and MMP9 protein expression in HUVECs. TNF-α also effectively increased the ERS-related molecules in HUVECs (GRP78, ATF4, caspase12 and p-PERK). EP treatment effectively reversed the effects of the TNF-α-induced adhesion of monocytes on HUVECs, inflammatory cytokines and ERS-related molecules. Furthermore, thapsigargin (THA, an ERS inducer) attenuated the protective effects of EP against TNF-α-induced inflammatory injury and ERS. The PERK siRNA treatment not only inhibited ERS-related molecules but also mimicked the protective effects of EP to decrease TNF-α-induced inflammatory injury. In summary, we have demonstrated for the first time that EP can effectively reduce vascular endothelial inflammation and that this effect at least in part depends on the attenuation of ERS.

Hyperbaric oxygen therapy is one of the most widely used clinical interventions to counteract insufficient pulmonary oxygen delivery in patients with severe lung injury. However, prolonged exposure to hyperoxia leads to inflammation and acute lung injury. This study aimed to investigate the protective effect of hydrogen sulfide on hyperbaric hyperoxia-induced lung injury. Rats were intraperitoneally treated with sodium hydrosulphide (NaHS) at 28 μmol/kg immediately before hyperoxia exposure and then exposed to pure oxygen at 2.5 atmospheres absolute (atm abs) with continuous ventilation for six hours, Immediately after hyperoxia exposure, rats were sacrificed via anesthesia. The bronchoalveolar lavage fluid (BALF) was harvested for the detection of protein concentration and IL-1 content, and the lungs were collected for HE staining, TUNEL staining and detection of wet/dry weight ratio. Our results showed hyperbaric hyperoixa exposure could significantly damage the lung (HE staining), increase the protein and IL-13 in the BALF, elevate the wet/dry Weight ratio and raise the TUNEL positive cells. However, pre-treatment with hydrogen sulfide improved the lung morphology, reduced the TUNEL positive cells and attenuated the lung inflammation (reduction in IL-13 of BALF and HE staining). Taken together, our findings indicate that hydrogen sulfide pretreatment may exert protective effects on hyperbaric hyperoxia-induced lung injury.

This study was undertaken to investigate the effect of edaravone inhalation on inflammasome activation in a rat hyperoxia-induced lung injury (HILI) model. Sprague Dawley rats (n = 61) were randomly assigned into three groups: Control group, HILI group and Edaravone (Eda) group. Rats in the Control group breathed room air, but those in the HILI group and Eda group were exposed to pure oxygen at 2.5 atmospheres absolute (atm abs) for six hours. Immediately after HILI, rats in the Eda group received inhalation of aerosol edaravone at 0.5 mg/ml for 30 minutes. Twenty-four hours later, rats were sacrificed. The bronchoalveolar lavage fluid (BALF) and lungs were obtained for detection of oxidative stress, IL-1beta, IL-18 and caspase-1; the lungs were collected for HE staining and TUNEL staining. The pathological features of the lungs of rats in the Eda group were significantly improved when compared with the HILI group, accompanied by reduction in apoptotic cells. In addition, in the Eda group, the malonyldialdehyde (MDA) was reduced and total antioxidant capacity (T-AOC) was increased significantly in the lung and BALF when compared with the HILI group (P < 0.05 for both). Moreover, the contents of IL-1beta, IL-18 and caspase-1 in the lung and BALF, downstream factors of inflammasome, were also dramatically lower in the Eda group than in the HILI group (P < 0.05 for all). These findings suggest that edaravone may inhibit inflammasome activation due to its anti-oxidative capacity exerting a protective effect on HILI.

ObjectiveHyperbaric oxygen (HBO) preconditioning (HBO-PC) has been testified to have protective effects on spinal cord injury (SCI). However, the mechanisms remain enigmatic. The present study aimed to explore the effects of HBO-PC on primary rat spinal neurons against oxidative injury and oxygen-glucose deprivation (OGD) and the relationship with heat shock proteins (HSPs).MethodsPrimary rat spinal neurons after 7 days of culture were used in this study. HSPs were detected in rat spinal neurons following a single exposure to HBO at different time points by Western blot. Using lactate dehydrogenase release assay and cell counting kit-8 assay, the injuries induced by hydrogen peroxide (H2O2) insult or OGD were determined and compared among neurons treated with HBO-PC with or without HSP inhibitors.ResultsThe results of Western blot showed that HSP27, HSP70 and HSP90 have a slight but not significant increase in primary neurons following HBO exposure. However, HSP32 expression significantly increased and reached highest at 12 h following HBO exposure. HBO-PC significantly increased the cell viability and decreased the medium lactate dehydrogenase content in cultures treated with H2O2 or OGD. Pretreatment with zinc protoporphyrin IX, a specific inhibitor of HSP32, significantly blocked the protective effects of HBO-PC.ConclusionsThese results suggest that HBO-PC could protect rat spinal neurons in vitro against oxidative injury and OGD mostly by up-regulating of HSP32 expression.

Oxygen therapy is one of the most widely used clinical interventions to counteract insufficient pulmonary oxygen delivery in patients with severe lung injury. However, prolonged exposure to hyperoxia at elevated partial pressure leads to inflammation and acute lung injury. The population at risk for this condition has markedly increased with the advent of efficient systems for delivery of high concentrations of oxygen in hospitals. Thus, the therapy of hyperoxia-induced lung injury has been a focus in studies of pediatrics and pulmonary medicine. In this paper, we briefly summarized the advances in the therapies of hyperoxia-induced lung injury on the basis of its pathogenesis. We hope our summary will help provide evidence for further investigation of therapeutic measures for hyperoxia-induced lung injury.

Mechanical ventilation with large tidal volumes can increase lung alveolar permeability and initiate inflammatory responses, termed ventilator-induced lung injury (VILI). VILI is characterized by an influx of inflammatory cells, increased pulmonary permeability, and endothelial and epithelial cell death. But the underlying molecular mechanisms that regulate VILI remain unclear. The purpose of this study was to investigate the mechanisms that regulate pulmonary endothelial barrier in an animal model of VILI. These data suggest that SC5b-9, as the production of the complement activation, causes increase in rat pulmonary microvascular permeability by inducing activation of RhoA and subsequent phosphorylation of myosin light chain and contraction of endothelial cells, resulting in gap formation. In general, the complement-mediated increase in pulmonary microvascular permeability may participate in VILI.

Oxygen is indispensable for all aerobic organisms and has become one of the most widely used therapeutic agents. Currently, oxygen not only is applied in the treatment of diseases, but becomes a modality for the prevention of some diseases. Hyperoxia preconditioning with normobaric or hyperbaric oxygen has been found to be protective in some diseases in several animal models and clinical trials. Currently, investigators pay increasing attention to the application of hyperoxia preconditioning in the prevention of common neurological diseases, and encouraging effectiveness has been achieved. In the present short review, we briefly described the development, application and mechanisms of hyperoxia preconditioning in the neurology, and the issues in future application of hyperoxia preconditioning were also proposed.

Xenon is one of noble gases and has been recognized as an anesthetic for more than 50 years. Xenon possesses many of the characteristics of an ideal anesthetic, but it is not widely applied in clinical practice mainly because of its high cost. In recent years, numerous studies have demonstrated that xenon as an anesthetic can exert neuroprotective and cardioprotective effects in different models. Moreover, xenon has been applied in the preconditioning, and the neuroprotective and cardioprotective effects of xenon preconditioning have been investigated in a lot of studies in which some mechanisms related to these protections are proposed. In this review, we summarized these mechanisms and the biological effects of xenon preconditioning.

Decompression sickness (DCS) is a major concern in diving and space walk. Hyperbaric oxygen (HBO) preconditioning has been proved to enhance tolerance to DCS via nitric oxide. Heat-shock protein (HSP) 70 was also found to have protective effects against DCS. We hypothesized that the beneficial effects of HBO preconditioning on DCS was related to levels of elevated HSP70. HSPs (70, 27 and 90) expressed in tissues of spinal cord and lung in rats was detected at different time points following HBO exposure by Western blot. HSP27 and HSP90 showed a slight but not significant increase after HBO. HSP70 increased and reached highest at 18 h following exposure before decreasing. Then rats were exposed to HBO and subjected to simulated air dive and rapid decompression to induce DCS 18 h after HBO. The severity of DCS, along with levels of HSP70 expression, as well as the extent of oxidative and apoptotic parameters in the lung and spinal cord were compared among different groups of rats pretreated with HBO, HBO plus NG-nitro-L-arginine-methyl ester (l-NAME), HBO plus quercetin or normobaric air. HBO preconditioning significantly reduced the morbidity of DCS (from 66.7% to 36.7%), reduced levels of oxidation (malondialdehyde, 8-hydroxyguanine and hydrogen peroxide) and apoptosis (caspase-3 and 9 activities and the number of apoptotic cells). l-NAME or quercetin eliminated most of the beneficial effects of HBO on DCS, and counteracted the stimulation of HSP70 by HBO. Bubbles in pulmonary artery were detected using ultrasound imaging to observe the possible effect of HBO preconditioning on DCS bubble formation. The amounts of bubbles in rats pretreated with HBO or air showed no difference. These results suggest that HSP70 was involved in the beneficial effects of HBO on DCS in rats, suspected be by the antioxidation and antiapoptosis effects.

Xenon is one of noble gases and has been recognized as an anesthetic for more than 50 years. Xenon possesses many of the characteristics of an ideal anesthetic, but it is not widely applied in clinical practice mainly because of its high cost. In recent years, numerous studies have demonstrated that xenon as an anesthetic can exert neuroprotective and cardioprotective effects in different models. Moreover, xenon has been applied in the preconditioning, and the neuroprotective and cardioprotective effects of xenon preconditioning have been investigated in a lot of studies in which some mechanisms related to these protections are proposed. In this review, we summarized these mechanisms and the biological effects of xenon preconditioning.

Hyperbaric oxygen (HBO) therapy refers to the breathing ofpure oxygen while in a sealed chamber that has been pres-surized at 1.5 to 3 times normal atmospheric pressure. Todate, HBO therapy has been applied in a series of diseaseswith potential hypoxia including decompression sickness,carbonmonoxidepoisoning,gasgangrene,osteomyelitis,andso on (http://en.wikipedia.org/wiki/Hyperbaric_medicine).However, cancer is not an indication for hyperbaric oxygenin both USA and China.Recently, Moen and Stuhr reviewed the evidence on theinfluence of HBO on cancers in past 9 years [1]. Their con-clusionwasconsistentwithtwoprevioussystemicreviewsonHBO and cancer that the use of HBO in patients with malig-nanciesisconsideredsafe.Inthisreview,theysummarizedtherelationship between hypoxia and cancer and the influence ofHBO on cell survival, angiogenesis, metastasis, chemothera-py,andradiotherapy.Finally,theyreviewedtheeffectofHBOon cancer cells of different types. Although they proposedsome explanations on the effects of HBO on cancers, themechanisms are more complex than we expected.HBO, hypoxia, and angiogenesisIt has been accepted that HBO can increase the dissolvedoxygen significantly, which may rectify the hypoxia incancers. However, HBO is often used once or twice dailyfor patients, and a hypoxic environment may form betweentwo exposures. As shown in this review, hypoxia is essentialfor the progression of cancers and related to the angiogen-esis. In addition, some studies have also shown that HBOtherapy can improve the angiogenesis after ischemic injury.Our previous study also revealed that HBO pretreatment canincrease the expression of hypoxia-inducible factor and itsdownstream factor vascular endothelial growth factor [2]which is a potent pro-angiogenic factor. Thus, HBO seemsto exert promotive effect on cancer growth.HBO and metastasisMetastasis is a complex process involving local cancer cellinvasion, entry into the blood or lymph vessels, and re-penetration and colonization at a distant site [3]. Theintegrity of vascular basement membrane (VBM) iscrucial for the cancer cell invasion. Suzuki et al. foundthat HBO enhanced transendothelial permeability in ratbrains [4]. In addition, HBO preconditioning was foundto increase the expression of matrix metalloproteinase(MMP) [5] which is may break the VBM. This maypotentiate the cancer cell invasion. Of interest, HBOtherapy may reduce the insult-induced expression ofMMP [6]. Thus, whether the effect of HBO on VBMintegrity depends on the microenvironment is not clear.If so, this may partially explain the absence of influenceof HBO on the metastasis of cancers.HBO and cancer stem cellsCancer stem cells (CSCs) are cancer cells that possesscharacteristics associated with normal stem cells, specifically

目前,医学教育改革要求构建知识、能力和素质三位一体的新型培养模式。单一的第一课堂已经很难满足这样的要求,内容丰富、形式多样的第二课堂已经成为高等教育不可或缺的组成。《潜水医学》是一门实践性很强的学科,其第二课堂也不同于其他的医学学科。近年来,在本科生第二课堂带教上进行了一些有益的尝试,在培养学生的科研思维能力、锻炼学生的实践能力、提升学生的创新能力和强化学生的团队精神上有一定的体会。