[Plasma level of apelin and carotid atherosclerosis in maintenance hemodialysis patients].

OBJECTIVE: To determine the plasma level of apelin in patients of maintenance hemodialysis (MHD) and to explore the relationship between apelin level and carotid atherosclerosis (AS) in MHD patients.
 Methods: A total of 92 MHD patients and 36 sex- and age-matched healthy subjects were enrolled in this study. The plasma level of apelin was evaluated by radiation immunoassay; serum endothelial injury markers including thrombomodulin, von Willebrand factor (vWF), and CD146, and inflammatory factors including high sensitive C-reactive protein (hsCRP), IL-6 and TNF-α were determined by ELISA. Common Carotid arteries intima media thickness (CCA-IMT), cross-sectional calculated intima-media area (cIM area) area and atherosclerotic plaque were measured by non-invasive high-resolution B-mode ultrasonography.
 Results: The plasma levels of apelin was significantly decreased in MHD patients compared with healthy subjects (P<0.01), accompanied with elevated plasma levels of thrombomodulin, vWF, CD146, hsCRP, IL-6 and TNF-α (all P<0.01). The plasma levels of apelinin in MHD patients with carotid artery plaques were obviously lower than those without plaques [(43.16±10.12) pg/mL vs (61.43±16.25) pg/mL, P<0.01]. Plasma level of apelin was inversely related with CCA-IMT and cIM area (r=-0.355 and r=-0.297 respectively, all P<0.01). Multiple stepwise regression analysis showed that plasma level of apelin was an independent risk factor for CCA-IMT and cIM area. 
 Conclusion: The plasma apelin in MHD patients might take part in vascular endothelial injury and the progress of atherosclerosis. It plays an important role in the initiation and development of uremia associated atherosclerosis through elevating inflammatory factors including hsCRP, IL-6 and TNF-α levels.

[Effect of calcitriol on secondary hyperparathyroidism].

OBJECTIVE: To investigate the calcium-phosphate metabolic condition in maintenance hemodialysis patients with chronic kidney disease (CKD), and to observe the effect of large dose calcitriol on secondary hyperparathyroidism (SHPT). METHODS: We tested and compared the serum levels of calcium, phosphate, intact parathyroid hormone (iPTH), and alkaline phosphatase (AKP) in hemodialysis patients at different hemodialysis time (Group A with hemodialysis period ≤3 years and Group B with hemodialysis period >3 years). We also detected those indexes before and after treating SHPT with large dose calcitriol. Twenty SHPT patients were divided into Group I (enlargement of parathyroid gland or nodule detected by color Doppler ultrasound) and Group II (normal parathyroid gland detected by color Doppler ultrasound). RESULTS: In the maintenance hemodialysis patients, the serum phosphate was (2.11±0.38) mmol/L and iPTH was (581.11±487.75) pg/mL. The serum level of iPTH in Group B was higher than that in Group A [(828.13±690.39) pg/mL vs (477.94±324.73) pg/mL, P<0.001]. In Group I, the serum level of iPTH [before vs after: (2471.7±898.3) pg/mL vs (2510.4±825.7) pg/mL] and AKP [before vs after: (524.2±18.8)U/L vs (511.3±19.3)U/L] did not change after the treatment of large dose calcitriol (P>0.05). In Group II, the serum level of iPTH [before vs after: (1358.5±302.8) pg/mL vs (369.3±43.4) pg/mL, P<0.001] and AKP [before vs after: (565.9±23.9)U/L vs (234.8±21.1)U/L, P<0.001] decreased significantly after the treatment of large dose calcitriol. CONCLUSION: Patients with longer time of hemodialysis have a higher level of iPTH. Large dose calcitriol can improve the clinical syndrome of SHPT, and decrease the level of iPTH and AKP in SHPT patients with normal parathyroid gland.

[Expression of Notch3 and hypertensive renal fibrosis].

OBJECTIVE: To examine the expression of notch3 in the kidneys of patients with primary hypertension and rats with spontaneous hypertension, and to explore the relationship of notch3 and hypertension renal fibrosis. METHODS: Thirteen patients with primary hypertension served as a primary hypertension group (HP group), and 15 patients with kidney tumor served as a control group (CP group). The spontaneous hypertensive rats served as a primary hypertension group (SHR group, n=6), and WKY rats served as a control group (WKY group, n=6). Masson stainning was used to examine the collagen in the kidneys in the SHR group and the WKY group. Immunohistochemical staining was used to detect the levels of Notch3 in kidneys of the patients and the rats. The expression of snail mRNA in the kidneys in the SHR group and the WKY group was examined by real-time PCR. RESULTS: Masson staining showed much more collagen in the SHR group than that in the WKY group (P<0.05); the expression of Notch3 in the HP group was much higher than that in the CP group ( 6.741±0.231 vs 0.763±0.358, P<0.01). The expression of Notch3 in the SHR group was much higher than that in the WKY group (5.487±0.774 vs 0.421±0.163, P<0.01), and The expression of snail mRNA was much higher in the SHR group than that in the WKY group (0.996±0.120 vs 0.208±0.090, P<0.01 ). CONCLUSION: Notch3 may be related to the occurrence of hypertension renal fibrosis.

Precise visualization and ROS-dependent photodynamic therapy of colorectal cancer with a novel mitochondrial viscosity photosensitive fluorescent probe.

BACKGROUND: Colorectal cancer (CRC) is a prominent global cancer with high mortality rates among human beings. Efficient diagnosis and treatment have always been a challenge for CRC management. Fluorescence guided cancer therapy, which combines diagnosis with therapy into one platform, has brought a new chance for achieving precise cancer theranostics. Among this, photosensitizers, applied in photodynamic therapy (PDT), given the integration of real-time imaging capacity and efficacious treatment feasibility, show great potential to serve as remarkable tools. Although much effort has been put into constructing photosensitizers for locating and destroying CRC cells, it is still in high need to develop novel photosensitizers to attain specific detection and fulfil effective therapy. METHODS: Probe HTI was rational synthesized for the diagnosis and treatment of CRC. Spectrometric determination was carried out first, followed by the 1O2 generation ability test. Then, HTI was displayed in distinguishing CRC cells from normal cells Further, the PDT effect of the photosensitizer was studied in vitro. Additionally, HTI was used in CRC BALB/c nude mice model to validate its viscosity labelling and tumor suppression characteristics. RESULTS: We successfully fabricated a mitochondrial targeting probe, HTI, together with remarkable viscosity sensitivity, ultralow background interference, and excellent 1O2 generation capacity. HTI was favorably applied to the viscosity detection, displaying a 11-fold fluorescent intensity enhancement in solvents from 1.57 cp to 2043 cp. Then, it was demonstrated that HTI could distinguish CRC cells from normal cells upon the difference in mitochondrial viscosity. Moreover, HTI was qualified for producing 1O2 with high efficiency in cells, supported by the sparkling signals of DCFH after incubation with HTI under light irradiation. More importantly, the viscosity labelling and tumor suppression performance in CRC CDX model was determined, enriching the multifunctional validation of HTI in vivo. CONCLUSIONS: In this study, HTI was demonstrated to show a sensitive response to mitochondrial viscosity and possess a high 1O2 generation capacity. Both in vitro cell imaging and in vivo tumor treatment trials proved that HTI was effectively served as a robust scaffold for tumor labeling and CRC cells clearance. This breakthrough discovery held immense potential for advancing the early diagnosis and management of CRC through PDT. By leveraging HTI's properties, medical professionals could benefit from improved diagnostic accuracy and targeted treatment in CRC management, ultimately leading to enhanced patient outcomes.

Fosinopril and valsartan intervention in gene expression of Klotho, MMP-9, TIMP-1, and PAI-1 in the kidney of spontaneously hypertensive rats.

OBJECTIVE: To determine the role of fosinopril and valsartan intervention in Klotho, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor (PAI-1) gene expression in hypertensive renal interstitial fibrosis (RIF) in the kidney tissue of spontaneously hypertensive rats (SHR). METHODS: We randomly divided 20 male 22-week-old SHR into 4 groups (5 in each group): a hypertension group (SHR group), a fosinopril group [Fos group, 10 mg/( kg · d) gavage], a valsartan group [Val group, 10 mg/( kg · d) gavage], and a fosinopril plus valsartan group [Fos + Val group, fosinopril 10 mg/( kg · d) + valsartan 50 mg/( kg · d) gavage]. Another five 22-week-old male Wistar Kyoto rats (WKY) were used as controls. Through monitoring the weight of the rats, tail artery pressure, 24-hour urine protein by fosinopril and/or valsartan intervention after the 8-week trial. RT-PCR and Western blot were used to detect the mRNA and protein expression of Klotho, MMP-9, TIMP-1, and PAI-1 in the kidneys. RESULTS: RT-PCR showed that in the SHR group, Klotho mRNA and protein expression were significantly decreased(P<0.01), while mRNA and protein expression of MMP-9, TIMP-1, and PAI-1 were significantly higher compared with the WKY group(P<0.01). With fosinopril and / or valsartan intervention, Klotho mRNA expression in the Fos group (P<0.01), Fos + Val group (P<0.01), Val group (P<0.05), Klotho protein expression in the Fos group(P<0.05), Fos + Val group (P<0.05), Val group (P<0.01), were significantly increased compared with those in the SHR group. The mRNA and protein expression of MMP-9, TIMP-1, and PAI-1 in the Fos group, Val group, and Fos + Val group were significantly lower than those in the SHR group (P<0.01). The expression of Klotho mRNA had negative correlation with the expression of MMP-9 mRNA (r= -0.864, P<0.01), TIMP-1 mRNA (r=-0.725, P<0.01) and PAI-1 mRNA (r=-0.785, P<0.01). The Klotho protein expression had negative correlation with the expression of MMP-9 protein (r=-0.614, P<0.05), TIMP-1 protein (r=-0.579, P<0.05), and PAI-1 protein (r=-0.552, P<0.05). CONCLUSION: Anti-aging gene Klotho and the genes related with extracellular matrix degradation gene MMP-9, TIMP-1, PAI-1 are involved in hypertensive renal injury. The expression of Klotho and MMP-9, TIMP-1, and PAI-1 is closely correlated. Fosinopril and valsartan which increase the Klotho mRNA and protein expression can alter the expression of Klotho-MMPs/TIMPs, which may be the main mechanism to prevent interstitial fibrosis.

[Application of continuous renal replacement therapy in the rescue of MODS patients].

OBJECTIVE: To investigate the effect of continuous renal replacement therapy (CRRT) on patients with emergency and serious diseases. METHODS: The patients were divided into 2 groups: Group A [71 patients with multiple organ dysfunction syndrome (MODS)] were treated by CRRT for 175 times. Group B (30 patients) were treated with common hematodialysis (HD). Blood urea nitrogen (BUN), serum creatinine (Scr), natrem (Na(+)), kalium (K(+)), chlorine (Clj), power of hydrogen (pH), bicarbonate (HCO3-), carbon dioxide partial pressure (PCO(2)), and oxygen pressure (PO(2)) were measured before and after the treatment. RESULTS: After the treatment, all patients' general state of health, water-electrolyte and acid base disorder were improved. The levels of BUN, Scr, K(+) (All P(s)<0.01), and Na(+) (P<0.05 in Group A, P<0.01 in Group B) were all lower and the levels of CO(2)CP (P<0.01 in Group A, P<0.05 in Group B) were higher than that before the pretherapy in both Group A and Group B. There was significant difference on the levels of BUN, Scr, K(+)(All P(s)<0.01), Cl(-) and CO(2)CP (All P(s)<0.05) between Group A and Group B, which indicated the therapeutic effect in Group A was better than that in Group B. Furthermore, the levels of pH, PO(2) and HCO(3)(-) were higher (P<0.01) and PCO(2) was lower (P<0.05) obviously than that before the CRRT in 30 patients with acute respiratory distress syndrome (ARDS) in Group A. Among the 9 patients with poisoning, 7 were alleviated completely and 2 died after the CRRT plus hemoperfusion (HP). The survival time of patients was lengthened in Group A. No blood or bleed aggravation occurred in patients with bleeding inclination or 48 h before the operation after using the method of heparin soaking the blood filter. CONCLUSION: CRRT has better curative effect on removing the toxin effectively, rapidly correcting the turbulence of water electrolyte and sour-alkali balance for patients compare with HD. At the same time, it can increase the level of PO(2) and reduce CO(2) retention, improve the lung function and brain edema, and increase the patient's survival rate. Using CRRT as early as possible is very important and it can improve the prognosis of the patients who had MODS or other dangers because the death rate of MODS patients is very high.

Improvement of awareness, treatment and control of hypertension among chronic kidney disease patients in China from 1999 to 2005.

Controlling hypertension is important to protect renal function and prevent cardiovascular disease in chronic kidney disease (CKD) patients. However, data on hypertension awareness, treatment and control among CKD patients are limited. Two nationwide surveys were conducted in China in 1999-2000 and 2004-2005 among, respectively, 1328 and 1244 adult, non-dialysis, hypertensive CKD patients, to assess the status of hypertension awareness, treatment and control and associated factors. A standard questionnaire was adopted, and blood pressure (BP) was measured by trained staff according to a standard protocol in both surveys. Compared with the data from 1999-2000, the data from 2004-2005 showed increased awareness (87.2 vs. 75.7%, P<0.001), treatment (85.9 vs. 80.4%, P=0.001) and control (30.0 vs. 21.1%, P<0.001, by the general threshold of BP<140/90 mm Hg; 7.7 vs. 5.9%, P=0.075, by an optimal threshold of BP<130/80 mm Hg) of hypertension. The odds ratios for general BP control were 1.4 (95% confidence index (CI), 1.1-1.7) for female gender, 1.1 (95% CI, 1.0-1.1) for high estimated glomerular filtration rate, 1.3 (95% CI, 1.1-1.6) for treatment in a local hospital, 2.8 (95% CI, 2.0-3.9) for hypertension awareness and 1.7 (95% CI, 1.4-1.9) for combined treatment. General physicians from local hospitals made greater contributions to the total improvement. Lack of treatment was mainly due to patients not recognizing the necessity for it. This is the first report of hypertension awareness, treatment and control among hypertensive CKD patients from a developing country. Improvement of awareness and general control of hypertension were demonstrated. Education of both physicians and patients regarding optimal BP control should be reinforced in the future.