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Background: Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease (CVD). However, the association between CKD and CVD risk in patients with type 2 diabetes mellitus (T2DM) in China has not yet been well investigated. This study aimed to determine the association of CKD with the risks of coronary heart disease (CHD) and stroke in a Chinese population with T2DM. Methods: A total of 1401 inpatients with T2DM at the Second Affiliated Hospital of Zhejiang University School of Medicine between April 2008 and November 2013 were included in this study. The CKD-Epidemiology Collaboration equation for Asians was used to classify CKD. The UK Prospective Diabetes Study risk engine was used to estimate the risks of CHD and stroke. Results: CHD risk was significantly increased with CKD stage (20.1%, 24.8%, and 34.3% in T2DM patients with no CKD, CKD Stage 1–2, and Stage 3–5, respectively; P < 0.001 for all). The stroke risk was also increased with CKD stage (8.6%, 12.7%, and 25.4% in T2DM patients with no CKD, CKD Stage 1–2, and Stage 3–5, respectively; P < 0.001 for all). Compared with no-CKD group, the odds ratios (ORs) for high CHD risk were 1.7 (P < 0.001) in the CKD Stage 1–2 group and 3.5 (P < 0.001) in the CKD Stage 3–5 group. The corresponding ORs for high stroke risk were 1.9 (P < 0.001) and 8.2 (P < 0.001), respectively. Conclusion: In patients with T2DM, advanced CKD stage was associated with the increased risks of CHD and stroke. Key words: Chronic Kidney Disease; Coronary Disease; Stroke; Diabetes Mellitus

Chemoresistance is common among patients with esophageal squamous cell carcinoma (ESCC). We investigated the effect and mechanism of insulin on enhancing anticancer functions of cisplatin in human esophageal cancer cell line EC9706.The viability of EC9706 cells exposed to cisplatin was assessed using MTT assay. The times T1, when the number of living cells reached a plateau and T2, when the number of living cells reached a new plateau after the addition of insulin were found. T1 and T2 plateau cells were stained by Annexin V-FITC/PI and monodansylcadaverin (MDC). Fluorescent microscopy was used to observe the expression of apoptosis and autophagy intuitively. Apoptotic ratio and fluorescent intensity were analysed by flow cytometry (FCM) quantitatively. Western blotting analysis was used to estimate the protein expression levels of AKT, mTOR, PI3K, PTEN, autophage related indicator LC3-II and autophage related protein Beclin1 changes that occurred in the course of treatment.A larger number of typical autophagosomes were detected in EC9706 cells exposed to cisplatin. Insulin can increase the apoptosis induced by cisplatin. Apoptotic ratio of T1 plateau cells ((32.6 ± 4.3)%) is significantly less than T2 plateau ((47.5 ± 5.6)%). MDC fluorescent intensity at T1 plateau (104.9 ± 13.2) was significantly higher than intensity at T2 plateau (82.6 ± 10.3). After cotreatment with insulin, the expression level of LC3-II, Beclin1 and PTEN in T2 plateau cells were significantly downregulated, but AKT, mTOR and PI3K expressions significantly upregulated compared with T1 plateau.Insulin could enhance cisplatin-induced apoptosis in human esophageal squamous cell carcinoma EC9706 cells related to inhibition of autophagy. The activation of PI3K/Akt/mTOR signaling pathway induced by insulin resulted in the suppression of autophagy in EC9706 cells, which may be attributed to the anticancer effects of cisplatin.

The extract of Ginkgo biloba leaves tablets, ginaton, is widely used in treating ischemic cerebrovascular disease in the clinic. This study aimed to investigate the expression of aquaporin-1 (AQP-1) in rat lung with ischemia/reperfusion injury after pretreatment with ginaton, and whether the pretreatment with ginaton reduces the acute lung injury caused by ischemia/reperfusion injury.Adult Wistar rats were divided into two groups. Some rats were used as donors (n = 20), the others as recipients (n = 20). Left lungs of donor rats were used for the isolated lung reperfusion model, which perfused only with low potassium dextran (LPD) solution as group A (n = 10); the others were pretreated with ginaton before reperfusion as group C (n = 10). Right lung of donor rat without any treatment was used as a control group (group B and group D, n = 10 for each group). After the model was established, the expression of AQP-1 in the lung tissues was examined by immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction.Immunohistochemical examination revealed that AQP-1 was expressed in endothelia. Immunoblotting demonstrated that the relative gray values of AQP-1 protein in groups A and C were 0.65±0.06, 0.88±0.11, respectively. The relative gray values of the mRNA expression in groups A and C were 0.30±0.08, 0.49±0.11, respectively. The expression of AQP-1 protein and mRNA in group C was significantly higher than in group A (P0. 05).The pretreatment with ginaton can reduce the acute lung injury caused by ischemia/reperfusion.

Tracheostomy should be considered to replace endotracheal intubation in patients requiring prolonged mechanical ventilation (MV). However, the optimal timing for tracheostomy is still a topic of debate. The present study aimed to investigate whether early percutaneous dilational tracheostomy (PDT) can reduce duration of MV, and to further verify whether early PDT can reduce sedative use, shorten intensive care unit (ICU) stay, decrease the incidence of ventilator associated pneumonia (VAP), and increase successful weaning and ICU discharge rate.A prospective, randomized controlled trial was carried out in a surgical ICU from July 2008 to June 2011 in adult patients anticipated requiring prolonged MV via endotracheal intubation. Patients meeting the inclusion criteria were randomly assigned to the early PDT group or the late PDT group on day 3 of MV. The patients in the early PDT group were tracheostomized with PDT on day 3 of MV. The patients in the late PDT group were tracheostomized with PDT on day 15 of MV if they still needed MV. The primary endpoint was ventilator-free days at day 28 after randomization. The secondary endpoints were sedation-free days, ICU-free days, successful weaning and ICU discharge rate, and incidence of VAP at day 28 after randomization. The cumulative 60-day incidence of death after randomization was also analyzed.Total 119 patients were randomized to either the early PDT group (n = 58) or the late PDT group (n = 61). The ventilator-free days was significantly increased in the early PDT group than in the late PDT group ((9.57 ± 5.64) vs. (7.38 ± 6.17) days, P0.05). The sedation-free days and ICU-free days were also significantly increased in the early PDT group than in the late PDT group (20.84 ± 2.35 vs. 17.05 ± 2.30 days, P0.05; and 8.0 (interquartile range (IQR): 5.0 - 12.0) vs. 3.0 (IQR: 0 - 12.0) days, P0.001 respectively). The successful weaning and ICU discharge rate was significantly higher in early PDT group than in late PDT group (74.1% vs. 55.7%, P0.05; and 67.2% vs. 47.5%, P0.05 respectively). VAP was observed in 17 patients (29.3%) in early PDT group and in 30 patients (49.2%) in late PDT group (P0.05). There was no significant difference between the two groups in the cumulative 60-day incidence of death after randomization (P = 0.949).The early PDT resulted in more ventilator-free, sedation-free, and ICU-free days, higher successful weaning and ICU discharge rate, and lower incidence of VAP, but did not change the cumulative 60-day incidence of death in the patients' anticipated requiring prolonged mechanical ventilation.

Non-heart-beating donor lung has been a promising source of lung transplantation. Many studies on non-heart-beating donor lungs are based on animal lung transplantation. In this study, we assessed by organ bath the effect of one-hour warm ischemia on the non-heart-beating donor lung in terms of the integrity of contractile and relaxant functions and tissue structures of pulmonic arteries and bronchi.Sixteen Swedish pigs were randomly classified into two groups: heart-beating donor group and 1-hour warm ischemia non-heart-beating donor group. Pulmonic and bronchial rings were taken from the isolated left lungs of the pigs. The pulmonic rings were stimulated by U-46619 (5.7 mol/L) and acetylcholine (10(-4) mmol/L) to assess the contractile abilities of smooth muscle and the endothelium-dependent relaxation response, respectively. As such, acetylcholine (10(-5) mmol/L) and natrium arachidonic acid (0.01%) were used to detect the contraction of bronchial smooth muscle and epithelium-dependent relaxation response. Meanwhile, the variances of precontraction tension of control groups were recorded to measure whether there was spontaneous relaxation during endothelium/epithelium-dependent relaxation course. Finally, papaverine solution (10(-4) mmol/L) was used to detect the non-endothelium/epithelium-dependent relaxant abilities of pulmonic and bronchial smooth muscles.There was no significant difference in the tension values of precontraction of pulmonic rings (P0.05), endothelium-dependent relaxation (P0.05), precontraction of bronchial rings (P0.05) and epithelium-dependent relaxation (P0.05) between the heart-beating donor group and the 1-hour warm ischemia non-heart-beating donor group. And the pulmonic and bronchial rings of each subgroup B had no spontaneous relaxation. Finally, papaverine solution relaxed the smooth muscle of all the rings completely.The results of this experiment suggest that the contractile and relaxant functions and tissue structures of pulmonic arteries and bronchi are not damaged after warm ischemia for 1 hour, and support the further study of non-heart-beating donor lung.

The optimal timing to start continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) patients has not been accurately established. The recently proposed risk, injury, failure, loss, end-stage kidney disease (RIFLE) criteria for diagnosis and classification of AKI may provide a method for clinicians to decide the "optimal timing" for starting CRRT under uniform guidelines. The present study aimed: (1) to analyze the correlation between RIFLE stage at the start of CRRT and 90-day survival rate after CRRT start, (2) to further investigate the correlation of RIFLE stage with the malignant kidney outcome in the 90-day survivors, and (3) to determine the influence of the timing of CRRT defined by RIFLE classification on the 90-day survival and malignant kidney outcome in 90-day survivors.A retrospective cohort analysis was performed on the data of 106 critically ill patients with AKI, treated with CRRT during a 6-year period in a university affiliated surgical intensive care unit (SICU). Information such as sex, age, RIFLE stage, sepsis, sepsis-related organ failure assessment (SOFA) score, number of organ failures before CRRT, CRRT time during SICU, survival, and kidney outcome conditions at 90 days after CRRT start was collected. According to their baseline severity of AKI at the start of CRRT, the patients were assigned to three groups according to the increasing severity of RIFLE stages: RIFLE-R (risk of renal dysfunction, R), RIFLE-I (injury to the kidney, I) and RIFLE-F (failure of kidney function, F) using RIFLE criteria. The malignant kidney outcome was classified as RIFLE-L (loss of kidney function, L) or RIFLE-E (end-stage kidney disease, E) using RIFLE criteria. The correlation between RIFLE stage and 90-day survival rate was analyzed among these three RIFLE-categorized groups. Additionally, the association between RIFLE stage and the malignant kidney outcome (RIFLE-L + RIFLF-E) in the 90-day survivors was analyzed.Fifty-three of the overall 106 patients survived to 90 days after the start of CRRT. There were 16, 22 and 68 patients in RIFLE-R, RIFLE-I and RIFLE-F groups respectively with corresponding 90-day survival rate of 75.0% (12/16), 63.6% (14/22) and 39.7% (27/68) (P0.01, compared among groups). The percentage of the malignant kidney outcome of 90-day survivors in the RIFLE-R, RIFLE-I, and RIFLE-F groups was 16.7% (2/12), 21.4% (3/14) and 55.6% (15/27), respectively (P for trend0.01). After adjustment for other baseline risk factors, the relative risk (RR) for the 90-day mortality significantly increased with baseline RIFLE stage. Patients in RIFLE-F had a higher RR of 1.96 (95% confidence interval (CI): 1.06 - 3.62) than patients in RIFLE-I (RR: 1.09, 95% CI: 0.55 - 2.15) compared with patients in RIFLE-R (P for trend0.01). Similarly, baseline RIFLE stage also significantly correlated with the odds ratio (OR) for the malignant kidney outcome in 90-day survivors (P for trend0.05). Ninety-day survivors in the RIFLE-F group had a borderline significantly highest OR of 6.88 (95% CI: 0.85 - 55.67).The RIFLE classification may be used to predict 90-day survival after starting CRRT and the malignant kidney outcome of 90-day survivors in the critically ill patients with AKI treated with CRRT. Starting CRRT prior to RIFLE-F stage may be the optimal timing. Prospective, multi-center, randomized controlled trials are needed to confirm its predictive value in these patients.

Background Previous studies have shown that oncosis in malignant tumors might be related to cellular energy supply. The aim of this study was to detect oncosis in human esophageal squamous cell carcinoma (ESCC), and to investigate its relationship with apoptosis and microvessel density (MVD). Methods ESCC specimens were obtained from 30 patients with ESCC after surgery. Transmission electron microscopy, TUNEL, and immunohistochemistry were used to detect oncosis, apoptosis, and MVD. The relation of oncosis to apoptosis and MVD was analyzed by ANOVA, t test, and q test using SPSS 10.0. Results Transmission electron microscopy revealed both oncosis and apoptosis in the ECSS tissues. About 10% of the TUNEL-positive cells, which were considered apoptotic cells, showed the characteristics of oncosis. In the areas, where oncotic cells accumulated, apoptotic cells were rare; contrarily, where apoptotic cells gathered, oncotic cells were sparse. Compared with the tissues with a high MVD, the number of oncotic cells was increased and that of apoptotic cells was decreased in the tissues with a low MVD. Conclusions Cellular oncosis can be detected in human ESCC tissues. The distribution of oncotic cells presents a close relationship with cellular apoptosis and MVD. Oncosis might be induced by poor blood supply.

Basic fibroblast growth factor (bFGF) plays important roles in retina degeneration, light injury, mechanical injury, especially in retina ischemia-reperfusion injury (RIRI). This study was to investigate the therapeutical effect of bFGF on RIRI and its mechanisms.Experimental RIRI was induced by increasing intraocular pressure (IOP) in the eyes of 48 rats. These rats were divided into normal control, ischemia-reperfusion and bFGF-treated groups. Histological and ultrastructural changes of in the retina of different groups were observed, and the number of retinal ganglion cells (RGCs) was quantitatively analyzed under microscopy. Apoptotic cells were detected using the TdT-dUTP terminal nick-end labeling (TUNEL) method. The expression of caspase-3 was determined by streptavidin peroxidase (SP) immunohistochemistry. Atomic absorption spectrum method was used to evaluate the intracellular calcium changes.At the early stage of retinal ischemia-reperfusion injury, retina edema in the treated group was significantly eliminated compared with the untreated ischemic animals. RGCs in the bFGF-treated group was more than those in the untreated ischemic group during the post-reperfusion stages. In ischemic group, apoptotic cells could be found at 6th hour after reperfusion and reached the peak at 24 hours. At 72nd hour no apoptotic cells could be found.The changes in caspase-3 expression had a similar manner. The intracellular calcium of rat retina began to increase at 1st hour, reached the peak at 24 hours, and began to decrease at 72 hours. The change of the three markers in the treatment group showed a similar pattern, but they were all relatively less obvious.Apoptosis may play a vital role in RIRI. bFGF may has therapeutical effects on RIRI by inhibiting the increase of intracellular calcium and caspase-3 expression.

To evaluate the methods used to diagnose and surgically treat ruptured aneurysm in sinus of Valsalva (RASV).Thirty-seven hospitalized patients with ruptured aneurysms in the sinus of Valsalva from September 1981 to April 2001, including 21 cases (56.7%) of RASV associated with ventricular septal defects (VSD) and 11 (29.7%) with aortic valvular prolapse were given surgical interventions. Under hypothermia and extracorporeal circulation, we successfully performed the surgical correction of RASV for all 37 patients VSD repair in 21 patients, aortic valvuloplasty in 6 and aortic valvular replacement in 2.There was no hospital deaths among these patients, although residual shunting occurred in two patients and acute renal failure was found one. Follow-up study of one month to 20 years in the patients undergoing repair of RASV revealed that the mostly individuals treated with operation obtained satisfactory cardiac function.Correct diagnosis of ruptured aneurysm in sinus of Valsalva should be confirmed immediately and surgical correction should be carried out as soon as possible.