Renal dysfunction frequently occurs in patients with portal hypertension and is linked to unfavorable clinical outcomes. Transjugular intrahepatic portosystemic shunt (TIPS) has the potential to enhance renal perfusion through portal decompression; however, factors predicting early improvement in renal function remain insufficiently defined. This retrospective, single-center study analyzed 188 consecutive patients with portal hypertension who underwent TIPS. Patients receiving renal replacement therapy or with baseline eGFR < 15 mL/min/1.73 m2 were excluded. The primary endpoint was early renal function improvement, defined as a > 10% reduction in serum creatinine within 7 days. Early renal function improvement was observed in 27.7% of the cohort. Lower baseline eGFR was independently associated with higher probability of improvement (adjusted OR: 0.980, 95% CI: 0.966-0.993; p = 0.004). Neither pre- nor post-TIPS portal venous pressure nor the magnitude of pressure reduction was significantly associated with renal response. Restricted cubic spline analysis indicated a linear inverse relationship between baseline eGFR and improvement probability. The multivariable model demonstrated modest discriminative ability (AUC 0.666). Baseline renal function was associated with early post-TIPS early renal function improvement, whereas intra-procedural portal pressure parameters were not predictive. These findings suggest that early renal function improvement following TIPS may predominantly reflect reversible functional impairment rather than established structural kidney injury.

IntroductionThe temporal dynamics of renal acclimatization during the sub-acute transition to high altitude remain poorly defined. Specifically, the relationship between structural integrity and functional adaptation under sustained hypobaric hypoxia is unclear. This study aims to characterize the time-dependent trajectories of renal remodeling and identify the critical biological window for potential intervention.MethodsMale Sprague-Dawley (SD) rats were randomized to a normobaric normoxia control group or a simulated hypobaric hypoxia group (5,000 m, PO2: 11.3 kPa) for 3, 7, 14, and 28 days (n=6/group). Renal filtration function was assessed via serum creatinine (CRE) and cystatin C (CysC), while tubular injury and systemic inflammation were evaluated using neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18). Structural alterations were quantified through hematoxylin and eosin (H&E) and Periodic Acid-Schiff (PAS) staining, with peritubular capillary (PTC) density assessed via immunohistochemistry. The temporal associations and exploratory biomarker discrimination were analyzed using restricted cubic spline (RCS) regression, Spearman correlation, and receiver operating characteristic (ROC) analyses.ResultsDespite stable gross kidney weight and length throughout the exposure, histological analysis revealed progressive microscopic injury. PTC density exhibited a continuous, time-dependent decline that was significantly inversely correlated with tubular injury scores and medullary congestion. Notably, glomerular morphometry exhibited a distinct biphasic response: an initial significant reduction in glomerular diameter at Day 3, followed by subsequent enlargement peaking at Day 14. Temporally, serum biomarkers showed heterogeneous and exploratory trajectories, whereas histological injury remained more persistent. CysC and CRE showed overall temporal variation, but Tukey-adjusted post hoc comparisons did not identify significant pairwise differences between individual time points. In the exploratory Day 3 ROC analysis, CRE showed no meaningful early discriminatory ability (AUC = 0.486, 95% CI: 0.124–0.848), whereas KIM-1 showed the highest AUC among the examined circulating biomarkers (AUC = 0.861, 95% CI: 0.641–1.000). However, DeLong pairwise comparisons did not remain statistically significant after Tukey correction, and these ROC findings should be interpreted as hypothesis-generating.ConclusionHypobaric hypoxia induces a distinct state of structure-function uncoupling, characterized by persistent microvascular rarefaction that antedates measurable systemic functional decline. The first week of exposure represents a biologically active phase of vascular remodeling and tubular stress. These findings suggest that relying solely on functional markers may underestimate the severity of sub-clinical renal injury in hypoxic environments, highlighting the potential value of integrating structural biomarkers for more accurate risk stratification.

Background Cerebral small vessel disease (CSVD) is a major vascular contributor to dementia, cognitive decline, gait impairment, mood disturbance and stroke. Maintenance hemodialysis (MHD) patients have a high CSVD prevalence with poor prognosis. However, the dynamic progressive features and associated risk factors of CSVD in MHD patients remain unclear. We aimed to explore the progression of CSVD subtypes and their associated risk factors in MHD patients. Method This prospective cohort study enrolled MHD patients from January to June 2023 at Beijing Shijitan Hospital. Clinical and dialysis-related data were collected. Transcranial Doppler (TCD) was used to monitor the mean flow velocity (MFV) of the middle cerebral artery during dialysis, and the MFV reduction rate during dialysis was calculated. The cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), and Lacunes on brain magnetic resonance imaging (MRI) were assessed at baseline and at the 12-month follow-up. Multivariate linear regression model was used to analyze the risk factors associated with the progression of CSVD. Results A total of 92 MHD patients were included in this study, with a mean age of (63.21 ± 8.21) years (40–85 years old) and 71 males (77.17%). Compared with baseline, significant progression was observed in CMBs, WMHs and Lacunes at the 12-month follow-up ( p < 0.05). Multivariate linear regression analysis showed that longer dialysis vintage, higher MVF reduction rate, and elevated hsCRP levels were significantly associated with CMBs progression ( B = 0.065, 95% CI : 0.021–0.109, p = 0.004; B = 19.274, 95% CI : 0.379–38.168, p = 0.046; B = 0.311, 95% CI : 0.068–0.554, p = 0.013). Aging and increased MVF reduction rate were associated with WMHs progression ( B = 0.023, 95% CI : 0.006–0.040, p = 0.010; B = 1.352, 95% CI : 0.156–1.636, p = 0.013). In addition, smoking status and diabetes mellitus were significantly linked to lacunars progression ( B = 0.896, 95% CI : 0.156–1.636, p = 0.018; B = 1.230, 95% CI : 0.414–2.045, p = 0.004). Conclusion In addition to age, dialysis vintage, diabetes mellitus and smoking, the reduction in cerebral blood flow during hemodialysis is an independent risk factor for the progression of CSVD in MHD patients.

BackgroundAs a state of metabolic and nutritional derangements, protein-energy wasting (PEW) is highly prevalent and associated with increased morbidity and mortality in hemodialysis patients. Fibroblast growth factor-23 (FGF-23) and Klotho have been proven to contribute to chronic kidney disease-mineral and bone disorder (CKD-MBD) in patients undergoing hemodialysis. Previous evidence suggested that FGF-23 and Klotho may also contribute to the malnutritional status among these patients; however, the inter-relationship between the FGF-23–Klotho axis and PEW remains unclear. Therefore, we conducted this cross-sectional study to evaluate the association between plasma FGF-23 and Klotho levels and PEW in hemodialysis patients and to explore whether these markers could predict the presence of PEW.MethodsPlasma concentrations of FGF-23 and Klotho were measured, and their associations with PEW were assessed. PEW was evaluated based on body weight, muscle mass, biochemical data, and protein and energy intake, according to the 2008 criteria from the International Society of Renal Nutrition and Metabolism (ISRNM).ResultsIn this study, 147 hemodialysis patients (mean age 61.05 ± 13.32 years) were enrolled, of whom 66 (44.90%) had PEW. PEW was significant positively correlated with FGF-23 (r = 0.403, p < 0.001), age (r = 0.225, p = 0.006), C-reactive protein (r = 0.236, p = 0.004), intact parathyroid hormone (r = 0.237, p = 0.004), and single-pool Kt/V (r = 0.170, p = 0.040), while it was negatively correlated with Klotho (r = −0.361, p < 0.001), hemoglobin (r = −0.215, p = 0.009), and serum creatinine (r = −0.278, p = 0.001). Logistic regression analyses showed that plasma FGF-23 and Klotho were independently associated with PEW, even after adjusting for covariables. The area under the ROC curve (AUC) of FGF-23 and Klotho in predicting PEW was 0.734 and 0.710 (p < 0.001), respectively. When the combination of FGF-23 and Klotho was used to predict PEW, its sensitivity was 81.8%, specificity was 60.5%, and the AUC was 0.746.ConclusionPlasma levels of FGF-23 and Klotho are associated with PEW in hemodialysis patients. Higher plasma FGF-23 levels and lower Klotho levels may serve as valuable predictors of PEW in these patients.

Acute kidney injury (AKI) is a common postoperative complication associated with increased mortality. The transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertension in patients with decompensated cirrhosis; however, the incidence and risk factors for AKI following TIPS in patients with cirrhosis have not been fully elucidated. We aimed to investigate the clinical features of AKI after TIPS in patients with cirrhosis. Data from 384 patients with decompensated cirrhosis who underwent TIPS treatment were retrospectively collected. AKI was defined using the criteria recommended by 2012 the clinical practice guideline of Kidney Disease Improving Global Outcomes (KDIGO). We conducted univariate and multivariate logistic regression analyses to evaluate the risk factors for AKI and the association between AKI and all-cause mortality. Of these 384 cirrhosis patients, 8.3

目的 评价沙库巴曲缬沙坦(SV)治疗老年维持性血液透析(MHD)患者慢性心力衰竭的临床疗效及安全性.方法 纳入2021年1月至12月在我院肾内科就诊的合并慢性心力衰竭的老年MHD患者82例,根据是否服用SV分为治疗组40例和对照组42例,治疗组服用SV治疗,对照组使用血管紧张素转化酶抑制剂或血管紧张素受体阻滞剂治疗,比较2组血压、N末端B型钠尿肽前体(NT-proBNP)及心脏超声指标左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、LVEF,采用多元有序logistic回归分析疗效的影响因素.结果 治疗组治疗后LVEF明显高于对照组,收缩压、舒张压、NT-proBNP、LVEDD、LVESD明显低于对照组(P<0.05).治疗组总有效率明显高于对照组(92.5％vs 64.3％,P<0.01),心力衰竭再住院率明显低于对照组(10.0％vs 28.6％,P<0.05).多元有序logistic回归分析显示,应用SV是影响治疗效果的独立因素(OR=2.166,95％CI:1.093～4.293,P=0.027).2组治疗后高钾血症发生率比较,差异无统计学意义(P>0.05).结论 SV能有效控制合并慢性心力衰竭的老年MHD患者血压,抑制心室重构,改善心脏功能,治疗中应该警惕高钾血症发生.

Objective:To investigate the association between body mass index (BMI) and waist circumference (WC) with all-cause mortality in middle-aged and elderly patients receiving maintenance hemodialysis (MHD).Methods:It was a prospective cohort study. The clinical data of MHD patients aged ≥50 years old from eleven hemodialysis centers from April to June 2017 in Beijing were analyzed. The patients were divided into low BMI group [body mass index (BMI)<18.5 kg/m 2], normal BMI group (18.5 kg/m 2≤BMI <24.0 kg/m 2), overweight group (24.0 kg/m 2≤BMI<28.0 kg/m 2) and obesity group (BMI≥28.0 kg/m 2) by BMI, and central obesity group (male ≥85 cm, female ≥80 cm) and normal WC group (male <85 cm, female <80 cm) by WC. Kaplan-Meier survival analysis method was used to compare the difference of all-cause mortality between those groups. Multivariate Cox regression model was used to analyze the association of BMI and WC with all-cause mortality. Results:A total of 613 MHD patients were enrolled, with age of (63.82±7.14) years old and 258 (42.09%) females. There were 46 (7.50%) patients in the low BMI group, 303 (49.43%) patients in the normal BMI group, 227 (37.03%) patients in the overweight group and 37 (6.04%) patients in the obesity group. In addition, 346 (56.44%) patients were categorized as central obesity. Kaplan-Meier survival analysis results showed that the all-cause mortality rates of low BMI group (log-rank χ2=13.571, P<0.001) and obesity group (log-rank χ2=6.664 P=0.010) were higher than that of normal BMI group, and the all-cause mortality rate of central obesity group was higher than that of normal WC group (log-rank χ2=5.698, P=0.017). Multivariate Cox regression analysis results showed that，besides the low BMI group and obesity group (with normal BMI group as a reference, HR=5.289, 95% CI 2.318-12.067, P<0.001; HR=5.360, 95% CI 2.088-13.760, P<0.001, respectively), normal BMI and overweight combined with central obesity were also independently correlated with all-cause mortality (with normal WC group as a reference, HR=2.605, 95% CI 1.199-5.663, P=0.016; HR=1.787, 95% CI 1.026-3.732, P=0.031, respectively). Conclusions:Lower and higher BMI or combined central obesity are independently associated with all-cause mortality in the middle-aged and elderly patients receiving MHD.

The serum intact parathyroid hormone (iPTH) is associated with the prognosis of hemodialysis (HD) patients, however, its optimal range for reducing mortality remains inconsistent. We designed a prospective cohort study of 346 incident HD patients to assess the association between different serum iPTH level and mortality. According to the Kidney Disease Outcomes Quality Initiative (K/DOQI) international guidelines (2003), we divided patients into three groups (iPTH < 150 pg/mL, 150–300 pg/mL and >300 pg/mL). During the median follow-up of 58 months, 157 patients (45.38%) died. Multivariate Cox regression analysis showed that iPTH < 150 pg/mL and >300 pg/mL were associated with all-cause and cardiovascular mortality. Then, we performed a sensitivity analysis of patients divided into 6 serum PTH levels groups according to the folds of the K/DOQI target range. Multivariate Cox regression analysis showed that patients with serum iPTH ≥750 pg/mL, 600–749 pg/mL, 450–599 pg/mL had significantly higher risk of all-cause and cardiovascular mortality compared with those with serum iPTH in the range of 150–299 pg/mL. The association between serum iPTH and mortality shows a U-shaped curve. The optimal serum iPTH level which confers the lowest risk of all-cause and cardiovascular mortality could range from 150 pg/mL to 450 pg/mL in this group of incident HD patients.

目的 分析维持性血液透析患者骨折事件发生的相关风险因素.方法 选取2017年1—3月首都医科大学附属北京世纪坛医院血液净化中心的198例维持性血液透析患者作为研究对象,回顾性收集患者临床及实验室资料并随访3年,按照是否发生骨折分为非骨折组和骨折组.比较两组患者的临床资料[性别、年龄、体质指数(BMI)等]及血红蛋白、血清白蛋白、总胆固醇、三酰甘油、血清校正钙、血磷、血清全段甲状旁腺激素(iPTH)、高敏C反应蛋白(hs-CRP)等实验室指标的差异,采用二元Logistic回归方法分析骨折事件发生的风险因素.结果 198例血液透析患者中,发生骨折40例,骨折发生率为6.73/100个病人年.骨折组患者的女性比例、年龄、iPTH<150 ng/L患者比例以及血清hs-CRP水平显著高于非骨折组;应用活性维生素D的比例、BMI、血清白蛋白水平以及150 ng/L≤iPTH<300 ng/L患者比例显著低于非骨折组(均P<0.05).多因素Logistic回归分析结果显示:高龄(每增加10岁)(OR=1.650,95％CI 1.069～2.544,P=0.022)、女性(OR=3.170,95％CI 1.281～7.848,P=0.013)、低血清白蛋白(每降低5 g/L)(OR=2.192,95％CI 1.254～3.832,P=0.006)、iPTH<150 ng/L(OR=5.785,95％CI 1.797～18.628,P=0.003)和iPTH≥300 ng/L(OR=5.914,95％CI 1.484～23.573,P=0.012)是骨折的独立风险因素,维生素D的使用(OR=0.215,95％CI 0.059～0.785,P=0.020)是其保护因素.结论 女性、高龄、iPTH水平异常降低或升高、低血清白蛋白是血液透析患者骨折的独立风险因素,活性维生素D的使用是其保护因素.

目的 探讨老年血液透析患者臂踝动脉脉搏波传导速度(brachial-ankle pulse wave velocity,baPWV)与认知功能障碍的相关性.方法 选择2019年1?3月首都医科大学附属北京世纪坛医院及北京市南口医院的血液透析患者266例,根据中文版蒙特利尔认知评估量表(Montreal cognitive assessment,MoCA)评分将患者分为认知功能正常组88例(MoCA≥26分)和认知功能障碍组178例(MoCA＜26分).收集相关临床资料,采用多因素logis-tic回归分析影响因素,用ROC曲线分析baPWV的预测效能.结果 与认知功能正常组比较,认知功能障碍组年龄、糖尿病和脑卒中比例、baPWV水平更高,透析时间更长,受教育程度和血红蛋白更低(P＜0.01).多元logistic回归显示,年龄、受教育程度、糖尿病、透析时间、血红蛋白、baPWV与认知功能障碍独立相关(OR=1.09,95％CI:1.04～1.14、OR=0.84,95％CI:0.73?0.97、OR=3.72,95％CI:1.60～8.68、OR=1.03,95％CI:1.01?1.04、OR=0.94,95％CI:0.91?0.97、OR=1.38,95％CI:1.23～1.56,P＜0.05,P＜0.01).baPWV评估患者认知功能的ROC曲线下面积为0.793,临界值为15.30 m/s(P＜0.01).结论 baPWV增高是老年血液透析患者认知功能障碍发生的独立风险因素,该指标对认知功能障碍具有较佳的预测作用.

Objective:To explore the related risk factors of aortic arch calcification (AoAC) and the relationship between AoAC and long-term outcome in maintenance hemodialysis patients.Methods:The patients who underwent hemodialysis in the Blood Purification Center of Beijing Shijitan Hospital Affiliated to Capital Medical University from March to June 2015 were recruited. Calcification of the aortic arch was estimated with plain chest radiology. The patients were divided into AoAC group and no-AoAC group. Multivariate binary logistic regression was used to analyze the influencing factors of AoAC. Kaplan-Meier analysis and Cox regression model were used to examine the association between AoAC and adverse prognostic events (all-cause death and cardiovascular events).Results:There were 157 hemodialysis patients included in this study, with age of (62.63±15.05) years (30-90 years old) and 85 males (54.14%). The median follow-up time was 54(20, 54) months. There were 99 cases (63.06%) in AoAC group and 58 cases (36.94%) in no-AoAC group. The age, proportion of diabetes history, serum corrected calcium and triglyceride levels in AoAC group were higher than those in no-AoAC group (all P<0.05), while the proportion of using active vitamin D, serum albumin and intact parathyroid hormone level were lower than those in no-AoAC group (all P<0.05). Multivariate logistic regression analysis showed that older age ( OR=1.109, 95% CI 1.067-1.152, P<0.001), diabetes ( OR=4.110, 95% CI 1.551-10.890, P=0.004), longer dialysis duration ( OR=1.026, 95% CI 1.010-1.043, P=0.001), higher systolic pressure ( OR=1.039, 95% CI 1.012-1.067, P=0.005) and higher triglycerides levels ( OR=1.932, 95% CI 1.148-3.125, P=0.013) were the independent risk factors of AoAC, and higher hemoglobin was a protective factor ( OR=0.967, 95% CI 0.938-0.998, P=0.035) of AoAC. Sixty-three cases (63.64%) died, and 78 cases (78.79%) had cardiovascular events in AoAC group. Fourteen cases (24.14%) died, and 12 cases (20.69%) had cardiovascular events in no-AoAC group. Kaplan-Meier analysis showed higher incidence rate of all-cause death (Log-rank χ2=22.499, P<0.001) and cardiovascular events (Log-rank χ2=50.797, P<0.001) in patients with AoAC. Multivariate Cox regression analysis showed AoAC was the independent risk factor of all-cause death ( HR=2.003, 95% CI 1.039-3.859, P=0.038) and cardiovascular events ( HR=5.642, 95% CI 3.003-10.600, P<0.001). Conclusions:Older age, diabetes mellitus, longer dialysis duration, hypertension, higher triglyceride levels and lower hemoglobin are significantly associated with AoAC. AoAC is the independent risk factor of all-cause death and cardiovascular events in maintenance hemodialysis patients.

目的 探讨老年血液透析患者血清全段甲状旁腺激素(iPTH)水平与心脑血管事件(CCVE)相关性.方法 选择2015年1?3月在我院规律血液透析的老年患者134例,根据血清iPTH水平分为低水平组(iPTH＜150.00 ng/L);中水平组(iPTH 150.00～300.00ng/L);高水平组(iPTH＞300.00 ng/L).随访5年,观察各组CCVE发生情况,用Kaplan-Meier生存曲线及Cox回归模型评价血清iPTH水平与CCVE的关系.结果 低水平组年龄、糖尿病比例高于中水平组和高水平组;血清白蛋白、血磷、服用活性维生素D比例低于中水平组和高水平组(P＜0.05,P＜0.01).Kaplan-Meier生存分析显示,血清iPTH低水平组和高水平组CCVE发生率显著高于中水平组(80.00％和67.50％vs 46.15％,x2=13.897,Plog-rank=0.001).多因素Cox回归分析显示,低水平组和高水平组患者CCVE发生风险是中水平组的1.992倍(95％CI:1.120～3.544,P =0.019)和2.216倍(95％CI:1.209?4.060,P=0.010).结论 血清iPTH降低或升高均是老年血液透析患者CCVE发生的独立危险因素.

BACKGROUND:M10 is a derivative of Myricetin by adding a hydrophilic glycosylation group. Our previous study revealed that M10 by oral administration prevented colitis-associated colonic cancer (CAC) through attenuating endoplasmic reticulum stress in mice. In current study, we evaluated the inhibitory effects of M10 on ulcerative colitis in mice model, the mechanism of M10 in preventing colitis was further investigated.METHODS:Mice model of ulcerative colitis was induced by continuous oral dextran sodium sulfate (DSS). M10 was given gavage once a day for 12 consecutive weeks. Disease activity index (DAI) was recorded by analyzing the symptoms of colitis. Intestinal barrier was analyzed by the Immunofluorescence staining assay. The structure of microvilli of intestinal epithelial cells was analyzed under Transmission electron microscopy (TEM). TEM assay was also performed to determine the formation of necroptosis in the colonic epithelium with ulcerative colitis. We performed Western blotting assay to analyze the IL-6 and NF-κB pathways, as well as the cytokine cascades related to TNF-α signaling pathway during necroptosis.RESULTS:M10 by oral administration demonstrated a prevention of ulcerative colitis, showing a significant decrease of DAI as compared to the model mice. Pathological analysis indicated that M10 attenuated the degree of colonic inflammation in colonic tissues. M10 restored the structures of intestinal barrier damaged by DSS. M10 prevented the activation of the IL-6 and NF-κB signaling pathways in the inflamed colonic epithelium. Further, M10 prevented necroptosis in the inflamed colonic mucosal cells through down-regulating the TNF-α pathway. Importantly, M10 demonstrated higher activities in preventing ulcerative colitis than Myricetin and control drug Mesalazine.CONCLUSIONS:Myricetin derivative M10 prevents chronic ulcerative colitis through inhibiting necroptosis. M10 could be developed as a promising drug for the treatment of chronic ulcerative colitis.

As ZnO nanoparticles have been applied in many fields, their biological risks on human health, of course, are worthy of our attention. Whether ZnO NPs have the risk and how colonic cells respond to the invaded ZnO NPs are still unknown. Herein, we evaluated the biological effects of ZnO NPs on colonic mucosal cells by in vitro and in vivo methods. IMCE cells, with APC mutation but phenotypically normal, demonstrated hyperproliferation through activating the CXCR2/NF-κB/STAT3/ERK and AKT pathways when exposed to ZnO NPs for 24 h. Long-term exposure of ZnO NPs resulted in the malignant transformation of IMCE cells, showing the morphological changes, anchorage-independent cell growth ability. Importantly, IMCE cells exposed to ZnO NPs subcutaneously grew and induced tumorigenesis in nude mice. In conclusion, exposure of ZnO NPs could induce malignant transformation of colonic mucosal cells through the CXCR2/NF-κB/STAT3/ERK and AKT pathways. We suggest that it was necessary to consider using the precautionary principle for gastrointestinal contact nanomaterials.

Ethnopharmacological relevance: Tongxinluo (TXL), which is a Chinese medicine rooted from traditional used herbs, has been used in clinic to treat cardiovascular and cerebrovascular diseases. However, it remains unknown whether TXL alleviates low pressure hypoxic pulmonary hypertension.Aim of the study: Here, we aimed to observe the influence of TXL on pulmonary hypertension in a rat model that exposed to high altitude environment characterized by low pressure hypoxia.Materials and methods: A total of 32 male Sprague-Dawley rats were divided into four groups: control group (normal pressure and normoxia), pulmonary hypertension group (PAH, the parameter is equal to that in altitude 5000 m), TXL group (rats living in environment equal to that at altitude of 5000 m received TXL treatment), vardenafil group (VDNF, rats living in environment equal to that altitude of 5000 m received vardenafil treatment). The high altitude environment was created in chamber by adjusting the inner pressure and oxygen content concomitantly. Before entering the chamber, the TXL group was given TXL (1.2 g kg(-1) d(-1)) for 28 days, and the VDNF group was given VDNF (0.1 g kg(-1) d(-1)) for 28 days. After 28 days, the mean pulmonary artery pressure (mPAP) and right ventricular pressure was measured using right heart catheterization. The weight of the right ventricle (RV), left ventricle (LV) and interventricular septum (IVS) was measured, and the right ventricular mass index was calculated. Lung tissue was subjected to hematoxylin and elastic fiber staining, and the medial wall thickness (MT), medial wall cross-sectional area (MA), MT%, and MA% were measured. Proliferative activity within the pulmonary arteries was quantified by Ki67staining.Results: After 28 days, as compared with that in normal control group, animals living in the chamber (PAH group) showed a significant increase in mPAP(47.5 mmHg versus 18 mmHg), RV/LV+IVS (0.45 versus 0.21) and MA% (78% versus 44%), respectively. Administration of TXL resulted in a significant decrease of 20 mmHg in mPAP, returning of RV/LV+IVS to 0.27, and a 40% reduction in MT% compared with that in PAH group. In the VDNF group, RV/LV+IVS and MT% was 0.268 and 38.77, significantly lower than that in PAH group. While, mPAP increased by 12.5 mmHg with treatment by VDNF. In contrast to the PAH group, alpha- Smooth Muscle Actin (alpha-SMA reduced by 19% in the TXL group (p=0.005) and 16% in the VDNF group (p=0.01). Ki67 expression in the VDNF group was significantly lower than the PAH group (P < 0.01). Ki67 expression in the TXL group was significantly lower than the PAH group (P < 0.01). Compared with the VDNF group, the indexes above reduced in the TXL group. Our results indicate that TXL significantly reduces pulmonary artery pressure, right ventricular hypertrophy, pulmonary small artery wall thickness, and luminal stenosis. In addition, smooth muscle proliferation markedly decreased and muscular artery decreased. However, TXL was unable to restore parameters to control levels.Conclusions: The automatic-adjusted low pressure hypoxic chamber was capable of establishing a pulmonary hypertension rat model at an altitude of 5000 m. Compared with VDNF, TXL decreased mPAP and right ventricular hypertrophy index (RVHI) in the pulmonary hypertension rat model, and prevented vascular remodeling by reducing small pulmonary artery thickening, smooth muscle thickening and proliferation. Thus, TXL may be a potential treatment for pulmonary hypertension.

Objective To investigate the effect of vardenafil on high altitude pulmonary hypertension in rats, and the possible mechanism thereof. Methods Thirty rats were randomly divided into three groups:control group with normal-pres?sure and normal-oxygen (group C), pulmonary hypertension group with low-pressure and low-oxygen (group P), and the group treated by vardenafil in low-pressure and low-oxygen condition (group V). The rats of group P and group V were ex?posed to low-pressure and low-oxygen condition in an auto-modulating hypobaric and hypoxic cabin to simulate 5 000 m high altitude environment (air pressure 50 kPa, oxygen concentration 10%) for 8 hours daily. Vardenafil (1 mg/kg) was given by gastrogavage to rats in group V once daily for 4 weeks, while the isodose distilled water was given by gastrogavage to rats in group C and group P. The mean pulmonary arterial pressure and right ventricular mass index were measured respectively after 4-week treatment. Morphologic changes of peripheral pulmonary artery were detected by light microscope. The serum levels of nitric oxide (NO) and endothelin-1 (ET-1) were detected as well. Results The pulmonary arterial pressure and right ventricular mass index were significantly higher in group P than those of group C and group V (P<0.05). The ratio of vascular medial wall thickness to external diameter (WT%) and the ratio of pulmonary artery wall area to tube area (WA%) were significantly increased in group P than those of group C and group V (P<0.05). Furthermore, the serum level of NO was significantly lower in group P than that of group C and group V, but the serum level of ET-1 was significantly increased compared with that of group C and group V (P<0.05). Conclusion Vardenafil can effectively reduce the pulmonary arteri?al pressure, and attenuate pulmonary vessels and right ventricle remodeling induced by high altitude pulmonary hypertension.

目的：观察不同时间服用雷米普利对患者血压水平及异常血压昼夜节律（非杓型）的作用，探讨患者最佳服药方式。方法选择非杓型高血压患者144例，随机分为晨起服药组和睡前服药组，晨起服药组7∶00，睡前服药组晚8∶00早给予雷米普利5 mg／d口服，分别于6个月、12个月复查24 h动态血压监测。观察两组血压变化、恢复杓型血压节律情况及晨峰血压。结果两组用药后24 h平均收缩压（ SBP）及舒张压（ DBP）均低于用药前（P＜0．05），但睡前服药组较晨起服药组晨峰血压下降更明显（P＜0．05）。结论不同时间服用雷米普利均能达到降压效果，但非杓型高血压患者夜间服药有利于恢复杓型血压节律，控制血压晨峰现象。

Objective:To study the effect of Tongxinluo on HIF-1α in rats with hypobaric and hypoxia pulmonary hypertension.Method:30 male SD rats weighing 200-250 g were randomly divided into three groups:control group with normal pressure and normal oxygen(control group),pulmonary hypertension group with low-pressure and low-oxygen(model group),and the group treated by Tongxinluo in low-pressure and low-oxygen condition(Tongxinluo intervention group).Each group included 10 rats.Auto-modulating hypobaric and hypoxic cabin was used to simulate 5000 mhigh altitude environment(air pressure 50 kpa,oxygen concentration 10%).Tongxinluo(1.2g/kg crude drug)was given by gastrogavage to rats in Tongxinluo intervention group once daily.Control group were exposed to normal-pressure and normal-oxygen in the same laboratory environment.4 weeks later,the mean pulmonary arterial pressure(mPAP)and right ventricular(RV)mass index were measured.Concentrations of HIF-1α,VEGF and ET-1 in blood were detected.Results:Compared with control group,mPAP,RV mass index and the levels of HIF-1α,VEGF,ET-1 in model group were significantly increased(P<0.05).Compared with model group,rats of Tongxinluo intervention group showed lower mPAP and RV mass index,and the levels of HIF-1α,VEGF and ET-1 decreased remarkably(P<0.05).There was no significant difference between control group and Tongxinluo intervention group in right ventricular hypertrophy index and the levels of serum HIF-1α and ET-1(P>0.05).Conclusion:Tongxinluo may influence the occurrence and development of hypobaric and hypoxia pulmonary hypertension by downregulated the level of HIF-1α.

目的：观察西地那非治疗肺动脉高压（ PAH）的效果及其对患者生活质量的影响。方法选择PAH患者98例，给予口服西地那非（20 mg，3次/d）6个月，给药前后分别进行超声心动图、6分钟步行试验（6MWT）及生活质量调查问卷SF-36评分等。结果与治疗前比较，治疗后6MWT延长，超声心动图中的左心房直径、三尖瓣环收缩偏移数值、左心室射血分数增加，Tei指数、右心室直径、右心房直径、肺动脉收缩压降低，P均＜0．05；SF-36评分8个领域中的5项均得到提高，P均＜0．05。结论西地那非治疗PAH有效，且可明显改善患者生活质量。