Individuals who reside at high altitudes for extended periods or those who visit these regions briefly frequently experience high-altitude response,which triggers a series of physiological and pathological changes in the body,ultimately causing altitude sickness.One of the most critical features of high-altitude environments is hypoxia.Recent studies have demonstrated that hypoxia-inducible factor 1(HIF-1)plays a central role in mediating the body's response to hypoxic conditions at high altitudes.HIF-1,a heterodimeric transcription factor composed of an oxygen-sensitive subunit α(HIF-1α)and a constitutively expressed subunit β(HIF-1β),directly regulates the expression of multiple target genes,thereby modulating various physiological processes essential for cellular adaptation to hypoxia.According to a substantial body of research,aberrant expression of HIF-1 is implicated in the pathogenesis and progression of various diseases,including altitude sickness,cardiovascular disorders,neurological conditions,inflammatory diseases,cognitive impairment,immune dysregulation,and cancer.In this review,we provided an in-depth examination of the structural characteristics and regulatory mechanisms governing HIF-1 expression,discussed its downstream target genes,and highlighted the inhibitors currently under development.Additionally,we summarized the pivotal role and underlying mechanisms of HIF-1 in the development of altitude sickness,particularly its regulatory role in the pathophysiological processes of high-altitude pulmonary edema(HAPE),high-altitude cerebral edema(HACE),and high-altitude pulmonary hypertension(HAPH).Through a thorough examination of the role of HIF-1,we aim to provide a theoretical foundation and potential therapeutic targets for the prevention and treatment of altitude sickness.

Idiopathic pulmonary fibrosis (IPF) is a common chronic interstitial fibrotic disease. During the fibrosis process, myofibroblasts are abnormally activated, collagen is deposited in large quantities and the biomechanical characteristics of lung tissue are significantly altered. In this paper, a systematic review about the changes in lung tissues, cellular biomechanical properties and biomechanical signals during the process of IPF was presented, and the in vitro reproduction of biomechanical features and therapeutic strategies for targeting biomechanics wassummarized, so as to provide references for clinical prevention and treatment of IPF.

Objective:To evaluate the effect of remifentanil on mitogen-activated protein kinase (MAPK) signaling pathway during intestinal epithelial cell apoptosis induced by intestinal ischemia-reperfusion (I/R) in rats.Methods:Thirty-six clean grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, aged 2 months, were divided into 3 groups ( n=12 each) by a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group) and remifentanil group (R group). Intestinal I/R was produced by occlusion of superior mesenteric artery for 1 h followed by reperfusion in anesthetized rats.At 30 min before ischemia, 0.2 μg·kg -1·min -1 of remifentanil was infused intravenously for 5 min , followed by infusion of normal saline for 5 min, repeating for 3 cycles in group R. At 2 h of reperfusion, blood samples were collected from right ventricle to measure the concentration of diamine oxidase (DAO). The animals were then sacrificed and the intestinal tissues were obtained for examination of pathological changes and scored according to Chiu, for calculation of intestinal epithelial cell apoptosis rate (by TUNEL), for determination of the expression of phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated p38 MAPK (p-p38 MAPK), cleaved caspase-3 and nuclear factor kappa B p65 (NF-κB p65) in nucleoprotein and for calculation of p-ERK/ERK ratio, p-JNK/JNK ratio and p-p38 MAPK/p38 MAPK ratio in the intestinal tissues. Results:Compared with group Sham, Chiu′s scores, serum DAO concentration, apoptosis rate, p-ERK/ERK ratio, p-JNK/JNK ratio and p-p38 MAPK/p38 MAPK ratio and the expression of cleaved caspase-3 and NF-κB p65 in the intestinal tissues were significantly increased in group I/R, and Chiu′s scores was increased ( P<0.05), and no significant change was found in serum DAO concentration, apoptosis rate, p-ERK/ERK ratio, p-JNK/JNK ratio, p-p38 MAPK/p38 MAPK ratio and the expression of cleaved caspase-3 and NF-κB p65 in the intestinal tissues in group R ( P>0.05). Compared with group I/R, Chiu′s scores, apoptosis rate, serum DAO concentration, p-ERK/ERK ratio and expression of cleaved caspase-3 and NF-κB p65 were significantly decreased in group R ( P<0.05). Conclusion:The mechanism by which remifentanil inhibits intestinal epithelial cell apoptosis induced by intestinal I/R is related to promoting activation of ERK in rats.

Objective To evaluate the role of peroxisome proliferator-activated receptor gamma (PPARγ) in exogenous protectin D1 ( PD1)-induced reduction of endotoxin-induced acute lung injury (ALI) in mice. Methods Thirty-two clean-grade healthy male BABL∕C mice, weighing 20-25 g, aged 6-8 weeks, were divided into 4 groups (n＝8 each) using a random number table method: sham operation group (group S), ALI group, PD1 group and PPARγ antagonist GW9662 group. Mice underwent oral tra-cheal intubation, normal saline was instilled, and 1 h later normal saline was injected via the tail vein in group S. Mice underwent oral tracheal intubation, lipopolysaccharide (LPS) 3 mg∕kg was instilled, and 1 h later normal saline was injected via the tail vein in group ALI. Mice underwent oral tracheal intubation, LPS 3 mg∕kg was instilled, and 1 h later PD1 200 ng was injected via the tail vein in group PD1. Mice un-derwent oral tracheal intubation, LPS 3 mg∕kg was instilled, and 1 h later GW9662 1 mg∕kg and PD1 200 ng were injected via the tail vein in group GW9662. Mice were sacrificed at 24 h after intratracheal instilla-tion of LPS, the left lung was lavaged with phosphate buffer solution, and the broncho-alveolar lavage fluid (BALF) was collected for determination of neutrophil count and concentrations of interleukin-1beta ( IL-1β), tumor necrosis factor-alpha ( TNF-α) and IL-6 ( by enzyme-linked immunosorbent assay). Right lung tissues were obtained and cut into sections which were stained with haematoxylin and eosin and exam-ined with a light microscope for microscopic examination of the pathological changes which were scored (lung injury score) and for determination of the expression of PPARγ in lung tissues. Results Compared with group S, the neutrophil counts in BALF, concentrations of IL-1β, TNF-α and IL-6 and lung injury score were significantly increased, and the expression of PPARγ was down-regulated in group ALI ( P＜0. 01). Compared with group ALI, the neutrophil counts in BALF, concentrations of IL-1β, TNF-α and IL-6 and lung injury score were significantly decreased, and the expression of PPARγ was up-regulated in group PD1 (P＜0. 01). Compared with group PD1, the neutrophil counts in BALF, concentrations of IL-1β, TNF-α and IL-6 and lung injury score were significantly increased, and the expression of PPARγ was down-regulated in group GW9662 ( P＜0. 01). Conclusion PPARγ activation is involved in exogenous protectin D1-induced reduction of LPS-induced ALI in mice.

Objective:To investigate the effect of Manchu medicine north-Schisandra chinensis polysaccharide (NSCP) on the human neutrophils treated by lipopolysaccharide (LPS) cultivated in vitro,and to elucidate its anti inflammatory mechanism.Methods:The neutrophilic inflammatory cell model was established with LPS.The experiment included control group,LPS group (1.0 mg · L-1) and NSCP group (1.25,2.50 and 5.00 g · L-1),the cells in NSCP group were first treated with LPS for 60 min,and then treated with different concentrations of NSCP.The levels of TNF-α in neutrophils were measured with ELISA and the apoptotic rates were detected by flow cytometry.Results:The level of TNF-a in LPS group was increased compared with control group (P＜0.05).The level of TNF-α in NSCP group was decreased compared with LPS group (P＜0.05).The apoptotic rate in LPS group was decreased compared with control group (P＜0.05);the apoptotic rates in NSCP group were increased with the increasing of time and dose,and the best effect was found 16 h after treatment with 5 g · L-1NSCP:the apoptotic rate in NSCP group was significantly increased compared with LPS group (P＜0.05).Conclusion:NSCP can perform the anti-inflammation effect through the suppression of LPS-induced TNF-α secretion in neutrophils and the promotion of neutrophils apoptosis.