Longitudinal observation of intraocular pressure variations with acute altitude changes.

BACKGROUND: Higher intraocular pressure (IOP) is a major risk factor for developing glaucoma, and the leading cause of irreversible blindness worldwide. High altitude (HA) may be involved in IOP, but the reported results were conflicting. Ascent to HA directly by plane from low altitude regions is an acute, effortless exposure. However, the effects of such exposure to different altitudes on IOP have rarely been reported. AIM: To investigate changes in IOP after rapid effortless exposure to HA in stages and compare it with systemic parameters. METHODS: Fifty-eight healthy subjects (116 eyes) were divided into three groups: 17 low-altitude (LA) residents [44 m above sea level (ASL)], 22 HA residents (2261 m ASL) and 19 very HA (VHA) residents (3750 m ASL). The LA group flew to HA first. Three days later, they flew with the HA group to VHA where both groups stayed for 2 d. Then, the LA group flew back to HA and stayed for 1 d before flying back to 44 m. IOP, oxygen saturation (SpO2) and pulse rate were measured. The linear mixed model was used to compare repeated measurements. RESULTS: IOP in the LA group significantly decreased from 18.41 ± 2.40 mmHg at 44 m to 13.60 ± 3.68 mmHg at 2261 m ASL (P < 0.001), and then to 11.85 ± 2.48 mmHg at 3750 m ASL (P = 0.036 compared to IOP at 2261 m ASL) and partially recovered to 13.47 ± 2.57 mmHg upon return to 44 m. IOP in the LA group at HA and VHA was comparable to that in the local residents (12.2 ± 2.4 mmHg for HA,11.5 ± 1.8 mmHg for VHA). IOP was positively associated with SpO2. CONCLUSION: IOP in the LA group gradually reduced as altitude elevated in stages and became comparable to IOP in local residents. Hypoxia may be associated with IOP, which deserves further study.

Identification of the Functional Autophagy-Regulatory Domain in HCLS1-Associated Protein X-1 That Resists Against Oxidative Stress.

HCLS1 Associated Protein X-1 (HAX1) promotes cell survival through attenuation of the damaged signals from endoplasmic reticulum and mitochondria, which are known as prominent intracellular compartments for the autophagic process under stress conditions. This study investigates whether autophagy can be upregulated in response to HAX1 overexpression and identifies the functional motif in HAX1 responsible for the autophagic induction. Autophagosome accumulation, mitochondrial membrane potential (Δψm), and apoptosis were assessed in HEK293 cells post transduction with full-length or truncated HAX1-encoding genes, while empty vector-transduced cells served as control. Upon the oxidative stress, the enhanced autophagy induction was observed in cells overexpressing HAX1, as well as HAX1 truncations that encode peptide segments ranging from amino acids 127-180 (AA127-180). This protective response was further supported by flow cytometry and Western Blot results, in which oxidative stress-induced Δψm dissipation and the programmed cell death were suppressed in HAX1-overexpressing cells, associated with reduced DNA fragmentation and decreased Caspase-9 cleavage. Interestingly, the HAX1-induced autophagy response was abrogated when AA127-180 was removed, compromising the antiapoptotic effects upon oxidative stress. Overall, these data indicate that autophagy induction is involved in HAX1-induced cell protective mechanism, and AA127-180 serves as the functional autophagy-regulatory domain of this antiapoptotic protein.

Paracrine effect of CXCR4-overexpressing mesenchymal stem cells on ischemic heart injury.

It has been reported that CXCR4-overexpressing mesenchymal stem cells (MSCCX4 ) can repair heart tissue post myocardial infarction. This study aims to investigate the MSCCX4-derived paracrine cardio-protective signaling in the presence of myocardial infarction. Mesenchymal stem cells (MSCs) were divided into 3 groups: MSC only, MSCCX4 , and CXCR4 gene-specific siRNA-transduced MSC. Mesenchymal stem cells were exposed to hypoxia, and then MSCs-conditioned culture medium was incubated with neonatal and adult cardiomyocytes, respectively. Cell proliferation-regulating genes were assessed by real-time polymerase chain reaction (RT-PCR). In vitro: The number of cardiomyocytes undergoing DNA synthesis, cytokinesis, and mitosis was increased to a greater extent in MSCCX4 medium-treated group than control group, while this proproliferative effect was reduced in CXCR4 gene-specific siRNA-transduced MSC-treated cells. Accordingly, the maximal enhancement of vascular endothelial growth factor, cyclin 2, and transforming growth factor-ß2 was observed in hypoxia-exposed MSCCX4 . In vivo: MSCs were labeled with enhanced green fluorescent protein (EGFP) and engrafted into injured myocardium in rats. The number of EGFP and CD31 positive cells in the MSCCX4 group was significantly increased than other 2 groups, associated with the reduced left ventricular (LV) fibrosis, the increased LV free wall thickness, the enhanced angiogenesis, and the improved contractile function. CXCR4 overexpression can mobilize MSCs into ischemic area, whereby these cells can promoted angiogenesis and alleviate LV remodeling via paracrine signaling mechanism.

[Bundle program of treatment for acute severe type high altitude disease].

OBJECTIVE: To discuss Bundle treatment of the acute severe type high altitude disease. METHODS: The prospective and randomized controlled trial was conducted. Two hundred and three patients with high altitude pulmonary edema (HAPE) or high altitude cerebral edema (HACE) met inclusion criteria were included, and were randomly divided into Bundle treatment group (n = 125) and conventional treatment control group (n = 78). Critical patients with multiple organ dysfunction syndrome (MODS) were admitted to intensive care unit (ICU); with respiratory failure or serious hypoxia of the patients were given mechanical ventilation (invasive or noninvasive); fluid resuscitation and vasoactive agents were given in the unstable hemodynamics patients; diuretics and continuous veno-venous hemofiltration were given in acute renal dysfunction or failure. The gastrointestinal bleeding and blood coagulation disorders were concerned. The hospital stay time, cure rate and mortality were compared according to the stages and classification of HAPE or HACE among two groups. RESULTS: The hospital stay time was significantly decreased 1.66 days in the Bundle treatment group (days: 5.28 ± 3.17) compared with conventional treatment control group (6.94 ± 4.05, P < 0.05), the cure rate was significantly increased 7.06% (96.80% vs. 89.74%, P < 0.05), mortality of severe and fatal patients were decreased 5.59% and 31.15%, the mortality of patients in Bundle treatment group was significantly lower than conventional treatment control group (3.20% vs. 10.26%, P < 0.05). CONCLUSION: The standardized treatment which was integrated with plateau medicine and critical care medicine can effectively reduce the mortality of critical or severe patients with HAPE or HACE.