Background The use of extracorporeal membrane oxygenation (ECMO) has expanded significantly, especially during the COVID-19 pandemic, but membrane lung (ML) function at high altitudes remains unexplored. This study aimed to determine whether ML oxygen delivery (V’O2ML) capacity during ECMO is lower in high-altitude Xining than at low-altitude Beijing in China. Methods In this prospective observational study, patients who received ECMO were categorized into the Xining or Beijing group based on treatment center. Patients were monitored for ML gas transfer on the third day of ECMO, and clinical outcomes were compared between the two groups. Results Sixty patients were enrolled, 30 in each group. V'O2ML was significantly lower in the Xining group than in the Beijing group (171 [130-203] ml/min vs. 210 [178-255] ml/min, p = 0.002). Mortality at 60 days showed no significant difference, but ML failure was higher in the Xining group (26.7% vs 6.7%, p = 0.038). V'O2ML was positively correlated with post-ML arterial partial pressure of oxygen (PaO2), hemoglobin, and fibrinogen and negatively correlated with D-dimer (all p < 0.001). Older age (OR, 1.075; 95% CI, 1.020-1.132, p = 0.007) and lower V’O2ML capacity (OR, 0.984; 95% CI, 0.974-0.995, p = 0.005) were independent risk factors for 60-day mortality. The optimal V'O2ML cutoff for survival was ≥205ml/min, with higher V'O2ML associated with better outcomes (p < 0.001). Conclusions High altitude is associated with lower V’O2ML capacity during ECMO, although it does not appear to increase short-term mortality. V'O2ML is an essential prognostic factor, and further research with larger cohorts and dynamic monitoring of V'O2ML across different altitudes is recommended. Trial Registration ClinicalTrials.Gov: NCT06152744. Registered 22 November 2023

ETHNOPHARMACOLOGICAL RELEVANCE:Deziyangxin (DZYX) is a classical Tibetan multi-herb prescription recorded in Jing Zhu Ben Cao and traditionally used for conditions characterized by blood stasis, phlegm-heat accumulation, and tumor-like masses. Despite its long-standing clinical use, the pharmacological basis underlying its potential anti-tumor activity remains insufficiently understood. AIM OF THE STUDY:This study aimed to evaluate the anti-tumor efficacy of DZYX in non-small cell lung cancer (NSCLC) and to explore its potential mechanisms with emphasis on tumor immune microenvironment modulation. MATERIALS AND METHODS:Serum pharmacochemistry was performed using LC-MS/MS to identify circulating constituents of DZYX. A syngeneic Lewis lung carcinoma (LLC) mouse model was established in mice, which were treated with DZYX by oral gavage at 78.5 mg/kg or 157 mg/kg for 25 days. Tumor growth and histopathology were evaluated, while transcriptomic analysis, network pharmacology, flow cytometry, and immunohistochemistry were used to investigate molecular pathways and immune cell infiltration. RESULTS:LC-MS/MS identified 167 circulating components derived from DZYX. DZYX treatment significantly suppressed tumor growth and induced tumor necrosis in LLC-bearing mice. Transcriptomic and enrichment analyses indicated modulation of chemokine signaling, T-cell activation, and innate immune pathways. Flow cytometry and immunohistochemistry further demonstrated increased infiltration of CD4+ and CD8+ T cells, NK cells, and B cells within tumor tissues and spleens. Enhanced intratumoral Granzyme B and IFN-γ signals suggested increased cytotoxic immune activity. CONCLUSIONS:DZYX exerts anti-tumor activity in NSCLC associated with remodeling of the tumor immune microenvironment and multi-pathway molecular regulation. These findings provide mechanistic support for the traditional use of DZYX in tumor-related disorders and highlight its potential as an immunomodulatory candidate for lung cancer therapy.

The mechanism underlying the protective effects of Acacetin (AC) against sepsis-induced diaphragmatic dysfunction (SIDD) remains to be elucidated. AC is present in several medicinal plants and has many pharmacological effects and has been reported to inhibit ferroptosis. This study aimed to investigate the role of AC in SIDD and clarify related mechanisms. In this study, SIDD models were established in vivo via cecal ligation and puncture (CLP) and in vitro using LPS-stimulated C2C12 cells. AC treatment significantly ameliorated diaphragmatic atrophy and ferroptosis in SIDD in vitro and in vivo. The protein expression levels of PI3K/AKT/NRF2 pathway components and atrophy-related markers were assessed by Western blotting, while the mRNA expression of atrophy-related genes was determined by RT-qPCR. Oxidative stress markers, JC-1 staining, C11-BODIPY staining, transmission electron microscopy, immunohistochemistry, immunofluorescence staining, and inflammatory cytokine assays were performed to assess oxidative stress and ferroptosis-related indicators, thereby verifying the protective role of AC in SIDD. Network pharmacology analysis predicted that AC may protect against SIDD by regulating the PI3K/AKT/NRF2 signaling pathway. Mechanistically, AC treatment restored the reduction of NRF2 expression and nuclear translocation in SIDD, as well as, the levels of downstream SLC7A11, HO-1 and GPX4. Notably, knockdown of NRF2 or administration of LY294002 in vitro, as well as ML385 treatment in vivo, abolished the protective effects of AC against SIDD. Collectively, these findings indicate that ferroptosis and oxidative stress are pivotal in SIDD, and AC was demonstrated to potentially alleviate SIDD by regulating the PI3K/AKT/NRF2 pathway.

Anemia is a frequently encountered condition in critically ill patients, and red blood cell transfusion serves as a critical therapeutic intervention aimed at restoring hemoglobin levels and improving tissue oxygenation. However, the optimal threshold for transfusion remains a subject of controversy, particularly regarding the comparison between restrictive (Hb 7-9 g/dL) and liberal (Hb > 9 g/dL) strategies. However, we should also consider a third option. This method focuses on the individual patient. Doctors adjust care based on the patient's specific symptoms and other health problems. The selection of the appropriate strategy is contingent upon specific clinical conditions, such as sepsis, acute coronary syndrome, or neurological injury. Current evidence and clinical guidelines predominantly favor a restrictive transfusion in hemodynamically stable patients, whereas a liberal strategy may benefit those with underlying cardiovascular disease. This review synthesizes recent trial data and guideline recommendations to facilitate evidence-based and individualized transfusion decision-making in the ICU, aiming to optimize the balance between risks and benefits across diverse critical care settings.

Background:Acacetin (AC) is a flavonoid compound with antiperoxidant, anti-inflammatory, and antiplasmodial activity. However, the solubility of AC is poor and nano acacetin (Nano AC) was synthesized. The intestinal mucosal barrier is impaired in sepsis rats, and the protective effects and mechanism of AC and Nano AC on the intestinal mucosal barrier are unclear. Methods:Cecal ligation and perforation (CLP) was used to induce sepsis in rats, and lipopolysaccharide (LPS)-stimulated intestinal epithelial cells were used to observe the effects of AC and our synthesized Nano AC on the amelioration of intestinal mucosal damage. The molecular docking technique was used to predict the binding energy of AC to thioredoxin reductase 1 (TRX1) signaling pathway proteins. TRX1 inhibitor (PX-12) was employed to elucidate the protective signaling pathway of Nano AC in LPS-stimulated intestinal epithelial cells. Results:Our synthesized Nano AC, with an average particle size of 17.18 ± 0.48 nm and an uptake rate of 95% in intestinal epithelial cells. The maximum binding capacity of AC to TRX1 was -6.82 kcal/mol, supporting the hypothesis that TRX1 is a potential target of AC. AC and Nano AC ameliorated the survival rate, intestinal mucosal damage score, pathological morphology, hepatic and renal function, and myocardial troponin levels, decreased serum levels of pyroptosis-related factors, upregulated TRX1, down-regulated NOD-like receptor protein 3 inflammasome (NLRP3), cysteinyl aspartate specific proteinase-11 (Caspase-11), Gasdermin D (GSDMD) in sepsis rats. They improved mitochondrial morphology and mitochondrial reactive oxygen species (ROS) levels, reduced pyroptosis levels, and upregulated TRX1, which adjusted NLRP3/ Caspase-11/ GSDMD signaling pathway in LPS-stimulated intestinal epithelial cells. Moreover, Nano AC was more effective. Conclusion:AC and Nano-AC can inhibit the NLRP3/Caspase-11/GSDMD signaling pathway by upregulating TRX1 to ameliorate intestinal mucosal injury in sepsis rats, and the effect of Nano AC is more prominent.

High altitude pulmonary edema (HAPE) is a common respiratory disease in the high altitude area, which is rapid and harmful. We firstly conducted a case-control study to assess the potential association of CYP4F2 gene polymorphisms with HAPE susceptibility in the Chinese Han population. The study recruited 238 patients with HAPE and 230 healthy controls in Northwest China. Genomic DNA was extracted from blood samples, and gene polymorphisms were detected using the Agena MassARRAY platform. Odds ratios (ORs), 95% confidence intervals (95% CIs), and P-value were used to evaluate the relationship between HAPE risk and CYP4F2 gene polymorphisms. Multi-factor dimension reduction (MDR) was used to assess the optimal interaction of CYP4F2 gene polymorphisms on HAPE risk. We found rs3093193 was shown to reduce the risk of HAPE (OR = 0.70, 95% CI = 0.52–0.93, P = 0.014), while rs12459936 was increased the susceptibility to HAPE (OR = 2.08, 95% CI = 1.33–3.26, P = 0.001). Age stratified analysis revealed that rs3093193 and rs12459936 were correlated with HAPE risk in people at age > 32 years old, and rs3093193 and rs3093110 were correlated with the HAPE risk in people at age ≤ 32 years old. Gender stratification analysis was found that rs3093193, rs12459936, and rs3093110 were all related to HAPE risk in males. A combination of rs12459936 and rs3093110 was the best multi-loci model with the highest testing accuracy. Our study is the first to provide the association between CYP4F2 gene polymorphisms and HAPE risk in the Chinese Han population.

目的 分析重症肺炎革兰阴性菌分离株的耐药性及碳青霉烯酶耐药基因携带情况,为临床治疗提供依据.方法 选取2016年1月-2021年7月青海大学附属医院收治的81例革兰阴性菌感染所致重症肺炎患者,分析检出革兰阴性菌的分布特征及耐药性,聚合酶链式反应(PCR)检测碳青霉烯酶耐药基因携带情况.结果 81例患者共分离出157株病原菌,鲍氏不动杆菌、肺炎克雷伯菌、铜绿假单胞菌为主要致病菌,分别占比46.50％、26.75％、12.10％;鲍氏不动杆菌对氨苄西林、氨曲南耐药率均为100.00％,对碳青霉烯类抗菌药物耐药率均为60.27％;铜绿假单胞菌对氨苄西林、哌拉西林耐药率均为100.00％,对碳青霉烯类抗菌药物耐药率均为57.89％;肺炎克雷伯菌对氨苄西林、头孢西丁、妥布霉素、头孢曲松耐药率均为100.00％,对碳青霉烯类抗菌药物耐药率均为35.71％;共检出碳青霉烯酶耐药菌株70株,KPC、OXA23、OXA51、NDM及VIM-2耐药基因携带率分别为 21.43％(15/70)、47.14％(33/70)、47.14％(33/70)、7.14％(5/70)、4.29％(3/70).结论 革兰阴性菌中鲍氏不动杆菌、肺炎克雷伯菌、铜绿假单胞菌为重症肺炎患者感染的主要致病菌,且KPC、OXA23、OXA51基因的携带可能是以上致病菌耐碳青霉烯类药物的主要机制.

Background Hypoxaemia plays an important role in the development of pulmonary artery hypertension (PAH). Patients with acute respiratory distress syndrome (ARDS) in a high-altitude area have different pathophysiological characteristics from those patients in the plains. The goal of our study was to explore the clinical characteristics of PAH secondary to ARDS in a high-altitude area.Methods This was a prospective study conducted in the affiliated Hospital of Qinghai University. Two investigators independently assessed pulmonary artery pressure (PAP) and right ventricular function by transthoracic echocardiography. Basic information and clinical data of the patients who were enrolled were collected. A multivariable logistic regression model was used to evaluate the risk factors for PAH secondary to ARDS in the high-altitude area.Results The incidence of PAH secondary to ARDS within 48 hours in the high-altitude area was 44.19%. Partial pressure of oxygen/fraction of inspired oxygen <165.13 mm Hg was an independent risk factor for PAH secondary to ARDS in the high-altitude area. Compared with the normal PAP group, the right ventricular basal dimensions were significantly larger and the right ventricular tricuspid annular plane systolic excursion was lower in the PAH group (right ventricular basal dimensions: 45.47±2.60 vs 40.67±6.12 mm, p=0.019; tricuspid annular plane systolic excursion (TAPSE): 1.82±0.40 vs 2.09±0.32 cm, p=0.021). The ratio of TAPSE to systolic PAP was lower in the PAH group (0.03±0.01 vs 0.08±0.03 cm/mm Hg, p<0.001).Conclusions The incidence of PAH in patients with ARDS in our study is high. PAH secondary to ARDS in a high-altitude area could cause right ventricular dysfunction.Trial registration number NCT05166759.

High-altitude pulmonary edema (HAPE) is a common acute altitude sickness. This study was designed to investigate the effect of MIR17HG polymorphisms on HAPE risk in the Chinese population. The Agena MassARRAY platform was used to genotype six single-nucleotide polymorphisms (SNPs) in the MIR17HG gene in 244 HAPE patients and 243 non-HAPE controls. The odds ratio (OR) and 95% confidence interval were used to evaluate the association between each MIR17HG polymorphisms and the risk of HAPE under a polygenetic model. Statistical analysis was performed using the χ2 test. Multifactor dimensionality reduction (MDR) analysis was used to analyze the impacts of SNP–SNP interactions on the risk of HAPE. According to the allele model, the HAPE risk of people with the rs7318578 A allele of MIR17HG was lower than that of people with the C allele (OR 0.74, p = 0.036).Logistic regression analysis of four models for all selected MIR17HG SNPs showed significant differences in the frequencies of rs7318578 (OR 0.74, p = 0.037) and rs17735387 (OR 1.51, p = 0.036) between cases and controls. The results of the sex stratification analysis showed that among males, rs17735387 in the MIR17HG gene is associated with an increased risk of HAPE. MDR analysis showed that the best combination model was a three-locus model incorporating rs72640334, rs7318578, and rs7336610. This study revealed the correlations between rs7318578 and rs17735387 on the MIR17HG gene and the risk of HAPE in the Chinese population, providing a theoretical basis for the early screening, prevention, and diagnosis of HAPE in high-risk populations.

BackgroundAcute respiratory distress syndrome（ARDS） is a common respiratory critical illness. The high altitude hypoxic environment has a great influence on its occurrence and development. Now we lack clear diagnostic definition of high altitude acute respiratory distress syndrome.To verify the application value of Berlin Definition plateau criteria of Acute Respiratory Distress Syndrome in Xining , Qinghai ( 2261m).MethodsRetrospective analysis of the clinical data of ARDS patients admitted to the Department of Critical Care Medicine of the Affiliated Hospital of Qinghai University from January 2018 to December 2018. The severity was divided according to the Berlin definition, the plateau standard, and the Zhang standard, and the differences of three standards were compared.ResultsIn this study, 512 patients with mechanical ventilation were selected. 229 patients who met the criteria of Berlin Definition plateau criteria , including 107 patients with mild ARDS (46.72%), 84 moderate patients (36.68%) and 38 severe ARDS patients (16.59%). Among 253 meet Berlin definition patients , 49(19.77%) were mild,148(58.50%) were moderate,and 56 (22.13%) were severe ARDS. There are 204 patients that meet Zhang criteria, among the 204 enrolled patients, 87(42.65%) were ALI and 117(57.35%) were ARDS. The AUROC of the Berlin Definition, the Plateau criteria and Zhang criteria were 0.6675 (95% CI 0.5866-0.7484), 0.6216 (95%CI 0.5317-0.7116) and 0.6050 (95% CI 0.5084-0.7016).ConclusionFor Xining, Qinghai, the Berlin Definition Plateau oxygenation index correction criteria can distinguish the severity of ARDS , but it needs to be enlarged and confirmed by multicenter clinical studies.

目的 基于Rho/Rho-kinase信号通路探讨丙泊酚减轻大鼠脑缺血再灌注损伤的效果.方法 SD大鼠100只分成:对照组、模型组、丙泊酚低、中、高剂量组(20.0、40.0、80.0 mg/kg),模型组、丙泊酚低、中、高剂量组建立脑缺血再灌注损伤模型,建模成功后,丙泊酚低、中、高剂量组给予相应剂量丙泊酚灌胃,对照组和模型组给予等体积生理盐水,持续给予4周,实验结束后,对每只大鼠进行神经功能缺损评分,行贴纸去除及平衡木行走实验,对大鼠海马区进行病理评分,同时测定大鼠脑组织中Rho、Rho-kinase mRNA和蛋白水平.结果 模型组神经功能缺损评分、双侧贴纸去除时间、平衡木过杆时间、海马组织病理评分、脑组织海马区Rho、Rho-kinase mRNA和蛋白表达水平明显高于对照组(P<0.05);丙泊酚各剂量组神经功能缺损评分、双侧贴纸去除时间、平衡木过杆时间、海马组织病理评分、脑组织海马区Rho、Rho-kinase mRNA和蛋白表达水平明显低于模型组(P<0.05);且随着丙泊酚给药剂量的增加,神经功能缺损评分、双侧贴纸去除时间、平衡木过杆时间、海马组织病理评分、脑组织海马区Rho、Rho-kinase mRNA和蛋白表达水平逐渐降低,剂量-效应关系明显(P<0.05).对照组海马区神经元细胞完整,排列紧密;模型组海马区神经元排列松散,细胞深染固缩,有片状坏死,神经细胞间质隔离;丙泊酚高剂组神经元细胞趋于正常;丙泊酚中、低剂量组较模型组而言,神经细胞疏松、固缩程度轻,神经元细胞核仁清楚可见.结论 丙泊酚能减轻大鼠脑缺血再灌注神经功能损伤;其机制与丙泊酚能抑制Rho、Rho-kinase mRNA和蛋白的表达进而抑制Rho/Rho-kinase信号通路的激活有关.

Extracorporeal membrane oxygenation (ECMO) is an extracorporeal life support technology with partial cardiopulmonary replacement function. It plays a more important role in all kinds of critical diseases that need extracorporeal life support. Qinghai belongs to the plateau area, with an average altitude of more than 3000 meters. Under such special environment of hypoxia and low pressure, the pathophysiology and clinical manifestations of serious cardiopulmonary diseases such as respiratory, circulatory failure, acute respiratory distress syndrome, high altitude pulmonary edema, acute myocardial infarction and fulminant myocarditis are different from those in the plain area, so as the treatment. Although medical resources and technology in Qinghai are relatively backward, ECMO technology has made great progress in recent years, and 31 cases have been completed so far. We now summarize the application of ECMO technology in Qinghai Province, so that ECMO technology would had a better application and development in the plateau area.

Background: CYP4F2 is potentially associated with High altitude pulmonary edema (HAPE) risk by regulating inflammatory mediator leukotriene B4 and arachidonic acid. However, the role of CYP4F2 in HAPE susceptibility remains unknown. For the first time, we conducted a case-control study to assess the potential association of CYP4F2 gene variants (rs3093193, rs12459936, rs3093144 and rs3093110) with HAPE susceptibility in Chinese Han population. Methods : The study included 238 BC patients and 230 healthy controls from northwest China. The polymorphisms selected in CYP4F2 gene were genotyped by Agena MassARRAY system. Odds ratios (ORs), 95% confidence intervals (95% CIs), and P values were used to evaluate the relationship between the two. Results : In the allele model and genotype model of the overall analysis, rs3093193 was shown to reduce the risk of HAPE ( P ＜ 0.05), while rs12459936 increased susceptibility to HAPE ( P ＜ 0.05). Age stratified analysis revealed that rs3093193 and rs12459936 were correlated with HAPE risk at age > 32 years ( P ＜ 0.05), and rs3093193 and rs3093110 were correlated with the HAPE risk at age ≤ 32 years ( P ＜ 0.05). Gender stratification analysis found that rs3093193, rs12459936 and rs3093110 were all related to HAPE risk in males ( P ＜ 0.05). Haplotype analysis illuminated that GCCG and CTC could increase HAPE risk at age ≤ 32 years and males, respectively ( P ＜ 0.05). Conclusions : Our research confirmed that CYP4F2 genes polymorphisms were implicated in HAPE susceptibility in Chinese Han population.

Abstract Background: High altitude pulmonary edema (HAPE) is a severe form of acute mountain sickness (AMS). The results of existing studies have shown that the onset of HAPE has obvious ethnic specificity and personal susceptibility, suggesting that the occurrence of HAPE is related to genetic factors. Therefore, six polymorphisms on MIR17HG were selected to investigate the effect of mutations on MIR17HG on HAPE in Chinese Han population.Materials and Methods: 487 healthy participants (244 participants had high altitude pulmonary edema, as the case group; and 243 participants had no symptoms of HAPE, as the control group) were genotyped via the Agena MassARRAY, and the relationship between polymorphisms on MIR17HG and HAPE risk was evaluated using a χ2 test with an odds ratio (OR) and 95% confidence intervals (CIs) in multiple genetic models.Results: In the allele model, we observed that lower risk (OR = 0.74, 95%CI: 0.56 - 0.98, p = 0.036) of the A allele for rs7318578 on the MIR17HG compared with the people with the C allele. Logistic regression analysis of four models for all selected MIR17HG SNPs between cases and controls showed significant differences for rs7318578 (OR = 0.74, 95%CI: 0.56 – 0.98, p = 0.037) and rs17735387 (OR = 1.51, 95%CI: 1.03 – 2.21, p = 0.036) in the HAPE population.Conclusion: rs7318578 and rs17735387 on MIR17HG were associated with the genetic susceptibility of HAPE in Chinese Han population.

Abstract Background Esophageal cancer (EC) is the leading cause of cancer‐related mortality worldwide. The underlying genetic risk factors remain unclear. The association between gene growth hormone receptor (GHR) and phospholipase C epsilon 1 (PLCE1) polymorphisms and the EC risk were identified in this study. Methods A total of 506 EC cases and 507 controls were included in this research. Two SNPs (rs6898743 of GHR and rs2274223 of PLCE1) were selected and genotyped. The associations between gene polymorphisms and the EC risk were assessed by logistic regression analysis. The databases RegulomeDB, GTEx, and UALCAN were used for functional annotations. Results In the allelic frequencies analysis, the rs6898743 of GHR was associated with decreased susceptibility of EC (OR = 0.83, 95% CI: 0.70–1.00, p = 0.049), while rs2274223 of PLCE1 was associated with increased 0.25‐fold EC risk (OR = 1.25, 95% CI: 1.02–1.53, p = 0.037). The “GC” genotype of rs6898743 was associated with a 0.24‐fold decreased risk of EC under co‐dominant model (OR = 0.76, 95% CI: 0.58–0.99, p = 0.046), and the “GA” genotype of rs2274223 was associated with increased EC risk under co‐dominant model (OR = 1.36, 95% CI: 1.04–1.77, p = 0.023). Using GTEx database, rs2274223 was found to be significant associated with increased PLCE1 expression (p = 4.1 × 10−7) in esophagus muscularis. The UALCAN database demonstrated that the GHR gene was under‐expressed in esophageal cancer tissues (p = 0.017). Conclusion The gene GHR and PLCE1 polymorphisms are associated with EC in the general population and the results need to be verified in future.

目的 探讨高原地区危重患者不同剂量右美托咪定镇静对血流动力学的影响.方法 选取2014年1月-2016年6月我院ICU收治的60例需要持续镇静的危重患者,按照随机数字表法分为非负荷剂量组(N组)和负荷剂量组(L组),应用无创血流动力学监测仪Nicom持续监测HR、MAP、CO、CI、SV、TPRI.结果 两组T1时间点HR、MAP、CO相比有明显差异(P<0.05);TPRI在T1、T2时点有明显差异(P<0.05);包括SV在内其余均无明显差异(P>0.05).两组各观察时点与T0点相比HR、MAP、TPRI均下降,SV均上升(P<0.05),CO、CI无明显差异(P>0.05).结论 对于高海拔地区危重病人来说,给予负荷剂量右美托咪定虽可维持良好的镇静效果,但对血流动力学影响明显;而持续泵入非负荷剂量右美托咪定较负荷剂量对患者的血流动力学影响较小,且可维持良好的镇静效果.

ELANE (Elastase, Neutrophil Expressed), which has been identified as an oncogene in various tumors, is associated with neutropenia, both cyclic and autosomal dominant forms. However, little is known about ELANE on leukemia progression. To better understand the role of ELANE in leukemia progression, the expression level of ELANE, as well as correlation and survival analyses, was performed in patients with leukemia. Gene expression of ELANE on the normal monocytes and myeloid leukemia samples was obtained and compared via Oncomine. Correlation of ELANE and proto-oncogenes includes MYC and TP53 was assessed. The clinical prognostic value of ELANE was found to be elevated using Metzeler Acute myeloid leukemia microarray. As a result, ELANE was found to be highly expressed in the leukemia samples compared to normal monocytes. ELANE was found to be positively correlated with MYC expression, whereas it was negatively correlated with TP53 expression. Additionally, high expression of ELANE was associated with a relatively shorter survival time in leukemia patients, suggesting that ELANE is an oncogene in leukemia development. In conclusion, ELANE acts as a pro-oncogene in leukemia, which provides a potential therapeutic target.

目的 探讨过表达血红素加氧酶-1(Heme Oxygenase-1,HO-1)对低氧训练小鼠骨骼肌纤维组成的影响.方法 将8 w雄性过表达HO-1转基因小鼠和野生小鼠分为6组:野生小鼠低氧静息组(C)、过表达HO-1转基因小鼠低氧静息组(H)、野生小鼠低氧训练30 d组(C+T30)、野生小鼠低氧训练60 d组(C+T60)、过表达HO-1转基因小鼠低氧训练30 d组(H +T30)和过表达HO-1转基因小鼠低氧训练60 d组(H+T60).低氧训练(海拔2261m.20m/min,坡度5°,60min/d,5d/w,30d和60d)结束后记录各组小鼠力竭运动时间;行ATP酶染色后计算各型肌纤维的面积百分比;用real time PCR、western blot法检测骨骼肌肌红蛋白(myoglobin)及PGC-1α表达量.结果 与各自静息组相比,低氧训练30 d组和60 d组小鼠力竭运动时间均延长(P＜0.05);与野生小鼠相比,过表达HO-1的转基因小鼠经低氧训练后力竭运动时间延长显著(P＜0.01).与C组相比,C+ T60组小鼠红肌纤维增多(P＜0.05);与H组相比,H+T30组和H+T60组小鼠红肌纤维均显著增多(P＜0.01);过表达HO-1转基因小鼠经过低氧训练后红肌纤维较野生小鼠增多显著(P＜0.01).与静息组小鼠相比,低氧训练后各组小鼠骨骼肌中myoglobin的表达增加(P＜0.05),同时伴随PGC-1α表达增加(P＜0.05),尤以过表达HO-1小鼠显著(P＜0.05).结论 过表达HO-1在低氧训练中可显著提高小鼠运动耐力,其机制可能是HO-1通过增加PGC-1α的表达促进骨骼肌红肌纤维增加实现的.

背景:近年对低氧训练机制的研究主要围绕低氧训练对机体血液系统的调节作用展开,但结果具有两面性,提示还有非血液系统调节机制.目的:探讨血红素加氧酶1在低氧训练中对小鼠骨骼肌线粒体含量及生物合成的调节作用.方法:SPF级8周龄雄性过表达血红素加氧酶1转基因小鼠20只,野生型小鼠20只,由兰州大学医学院提供.2种小鼠分别被随机分为2组(共4组):野生小鼠低氧静息组、野生小鼠低氧训练组、转基因小鼠低氧静息组和转基因小鼠低氧训练组.低氧训练组小鼠在青海大学基础医学研究中心进行跑台运动(速度20 m/min,坡度5°,60 min/d,5 d/周,共4周).各组小鼠均于末次训练结束3 d后行速度20 m/min,坡度5°持续跑台运动并记录各组小鼠力竭运动时间,电镜检测骨骼肌线粒体数量,JC-1荧光探针检测线粒体膜电位,萤光素酶发光法检测线粒体ATP合成活性,Western blot检测骨骼肌血红素加氧酶1、COX IV和PGC-1α蛋白表达量.结果与结论:①与野生小鼠低氧静息组相比,野生小鼠低氧训练组和转基因小鼠低氧训练组力竭运动时间增加,线粒体数目略有增多,线粒体膜电位和ATP合成增加,血红素加氧酶1、COX IV和PGC-1α蛋白表达量增加;②与野生小鼠低氧训练组相比,转基因小鼠低氧训练组力竭运动时间明显增加,线粒体数目显著增多,线粒体膜电位和ATP合成增加,COX IV和PGC-1α蛋白表达量显著增加;③结果说明,血红素加氧酶1在低氧训练中具有延长小鼠力竭运动时间的作用,其机制可能与增加骨骼肌线粒体数量和生物合成有关.