The mechanism underlying the modulatory effect of substance P (SP) on GABA-activated response in rat dorsal root ganglion (DRG) neurons was investigated. In freshly dissociated rat DRG neurons, whole-cell patch-clamp technique was used to record GABA-activated current and sharp electrode intracellular recording technique was used to record GABA-induced membrane depolarization. Application of GABA (1–1000 μmol/L) induced an inward current in a concentration-dependent manner in 114 out of 127 DRG neurons (89.8 %) examined with whole-cell patch-clamp recordings. Bath application of GABA (1–1000 μmol/L) evoked a depolarizing response in 236 out of 257 (91.8%) DRG neurons examined with intracellular recordings. Application of SP (0.001–1 μmol/L) suppressed the GABA-activated inward current and membrane depolarization. The inhibitory effects were concentration-dependent and could be blocked by the selective neurokinin 1 (NK₁) receptors antagonist spantide but not by L659187 and SR142801 (1 μmol/L, n=7), selective antagonists of NK₂ and NK₃. The inhibitory effect of SP was significantly reduced by the calcium chelator BAPTA-AM, phospholipase C (PLC) inhibitor U73122, and PKC inhibitor chelerythrine, respectively. The PKA inhibitor H-89 did not affect the SP effect. Remarkably, the inhibitory effect of SP on GABA-activated current was nearly completely removed by a selective PKC_ε inhibitor epilon-V1-2 but not by safingol and LY333531, selective inhibitors of PKC_α and PKC_β. Our results suggest that NK₁ receptor mediates SP-induced inhibition of GABA-activated current and membrane depolarization by activating intracellular PLC-Ca²⁺-PKC_ε cascade. SP might regulate the excitability of peripheral nociceptors through inhibition of the “pre-synaptic inhibition” evoked by GABA, which may explain its role in pain and neurogenic inflammation.

The purpose of this study was to investigate the potential cardioprotection roles of Rapamycin in anoxia/reoxygenation (A/R) injury of cardiomyocytes through inducing autophagy, and the involvement of PI3k/Akt pathway. We employed simulated A/R of neonatal rat ventricular myocytes (NRVM) as an in vitro model of ischemial/reperfusion (I/R) injury to the heart. NRVM were pretreated with four different concentrations of Rapamycin (20, 50, 100, 150 μmol/L), and pretreated with 10 mmol/L 3-methyladenine (3MA) for inhibiting autophagy during A/R. Then, Western blot analysis was used to examine variation in the expression of LC3-II, LC3-I, Bim, caspase-3, p-PI3KI, PI3KI, p-Akt and Akt. In our model, Rapamycin had a preferential action on autophagy, increasing the expression of LC3-II/LC3-I, whereas decreasing the expression of Bim and caspase-3. Moreover, our results also demonstrated that Rapamycin inhibited the activation of p-PI3KI and enhanced the activation of p-Akt. It is concluded that Rapamycin has a cardioprotection effect by inducing autophagy in a concentration-dependent manner against apopotosis through PI3K/Akt signaling pathway during A/R in NRVM.

This study investigated the relationship between IL-33/ST2 signal pathway gene polymorphisms and myocardial infarction (MI) in Han Chinese. A case-control association analysis was performed on a total of 490 MI patients (MI group) and 929 normal subjects (NC group). Sequenom Mass Array and Taqman genotyping technique were used to analyze the tag single nucleotide polymorphisms (SNPs) in the genes encoding IL-33, ST2, and IL-1RaP (rs11792633, rs1041973 and rs4624606). The results showed that the frequencies of rs4624606 genotypes AA, TT, AT were 0.031, 0.647, 0.322 in MI group and 0.026, 0.712, 0.263 in NC group, and the allele frequencies of A and T were 0.192, 0.808 in MI group and 0.157, 0.843 in NC group. There were significant differences in rs4624606 genotypes and allele frequencies between MI group and NC group (P<0.05). For rs11792633, the allele frequencies of C and T were 0.45, 0.55 in MI group and 0.454, 0.546 in NC group with no significant differences found between the two groups. Compared with genotype CC+TC, rs11792633 genotype TT had an increased risk of hypertension (P<0.05). However, there were no significant differences in the frequencies of rs11792633 genotypes between the two groups. No significant differences were noted in the frequencies of rs1041973 genotype and allele between the two groups. Logistic regression analysis showed that rs4624606 genotypes AT and AA+AT were both significantly associated with MI (AT: OR=1.325, P=0.029, 95% CI=1.03–1.705; AA+AT: OR=1.316, P=0.028, 95% CI=1.03–1.681) after factors such as age, gender, smoking, drinking, body mass index (BMI), triglyceride (TG) and cholesterol were adjusted. Those carrying rs4624606 genotype AT or AA+AT had an increased risk of MI. No associations were found between the polymorphisms of the other two loci with MI. It was concluded that, in the IL33/ST2 signal pathway, the A allele of rs4624606 polymorphism of IL-1RaP gene is a potential independent risk factor for MI, and the genotypes AA+AT and AT are associated with the incidence of MI.

The chronic effects of carboxyl-terminal polypeptide of Cardiotrophin-1 (CT-1-CP) on ventricular electrical remodeling were investigated. CT-1-CP, which contains 16 amino acids in sequence of the C-terminal of Cardiotrophin-1, was selected and synthesized, and then administered to Kunming mice (aged 5 weeks) by intraperitoneal injection (500 ng·g⁻¹·day⁻¹) (4 groups, n=10 and female: male=1:1 in each group) for 1, 2, 3 and 4 weeks, respectively. The control group (n=10, female: male=1:1) was injected by physiological saline for 4 weeks. The epicardial monophasic action potential (MAP) was recorded by using a contact-type MAP electrode placed vertically on the left ventricular (LV) epicardium surface, and the electrocardiogram (ECG) signal in lead II was monitored synchronously. ECG intervals (RR, PR, QRS and QT) and the amplitude of MAP (Am), the maximum upstroke velocity (Vmax), as well as action potential durations (APDs) at different repolarization levels (APD₃₀, APD₅₀, APD₇₀, and APD₉₀) of MAP were determined and analyzed in detail. There were no significant differences in RR and P intervals between CT-1-CP-treated groups and control group, but the PR segment and the QRS complex were greater in the former than in the latter (F=2.681 and 5.462 respectively, P<0.05). Though QT interval and the corrected QT interval (QTc) were shorter in CT-1-CP-treated groups than in control group, the QT dispersion (QT_d) of them was greater in the latter than in the former (F=3.090, P<0.05) and increased with the time. The ECG monitoring synchronously with the MAP showed that the compression of MAP electrode on the left ventricular epicardium induced performance similar to myocardium ischemia. As compared with those before chest-opening, the PR segment and QT intervals remained basically unchanged in control group, but prolonged significantly in all CT-1-CP-treated groups and the prolongation of QT intervals increased gradually along with the time of exposure to CT-1-CP. The QRS complex had no significant change in control group, one-week and three-week CT-1-CP-treated groups, but prolonged significantly in two-week and four-week CT-1-CP-treated groups. Interestingly, the QT_d after chest-opening was significantly greater than that before chest-opening in control group (t=5.242, P<0.01), but decreased along with the time in CT-1-CP-treated groups. The mean MAP amplitude, Vmax and APD were greater in CT-1-CP-treated groups than those in control group, and became more obvious along with the time. The APD in four CT-1-CP-treat groups was prolonged mainly in middle to final repolarization phase. The difference among these groups became significant in middle phase (APD₅₀) (F=6.076, P<0.01) and increased furthermore in late and final phases (APD₇₀: F=10.054; APD₉₀: F=18.691, P<0.01) along with the time of injection of CT-1-CP. The chronic action of CT-1-CP might induce the adapting alteration in cardiac conductivity and ventricular repolarization. The amplitude and the Vmax of the anterior LV epicardial MAP increased obviously, and the APD prolonged mainly in late and final phase of repolarization.

This study was aimed to investigate the effect of stress induced by high-intensity exercises on the cardiovascular system. In the epidemiological investigation, 200 subjects (test group) engaged in special high-intensity exercises, and 97 who lived and worked in the same environment and conditions as those in the test group, but did not participate in the exercises served as controls. In the second part of the study, 50 mice were randomly divided into control group, exhaustive swimming group, white noise group, exhaustive swimming plus white noise group, and pioglitazone intervention group. The results showed that the plasma concentrations of the myocardial injury markers heart fatty acid-binding protein (H-FABP), C-reactive protein (CRP), β-endorphin (β-EP) and levels of psychological stress were significantly increased in test group as compared with control group; special high-intensity exercises resulted in a significant elevation of the incidence of cardiac arrhythmias. Animal experiments showed that the plasma levels of corticosterone (CORT) and troponin I (TnI) were raised while the level of SOD was reduced in exhaustive swimming group, white noise group, and exhaustive swimming plus white noise group. The expression levels of PPARγ mRNA and protein were decreased in myocardial tissues in these groups as well. HE staining showed no remarkable change in myocardial tissues in all the groups. Treatment with pioglitazone significantly decreased the plasma levels of TnI and CORT, while increased the level of SOD and the expression levels of PPARγ mRNA and protein. It was concluded that the high-intensity exercises may induce a heavy physical and psychological stress and predispose the subjects to accumulated fatigue and sleep deprivation; high-intensity exercises also increases the incidence of arrhythmias and myocardial injury. PPARγ may be involved in the physical and psychological changes induced by high-intensity exercises.

CD151 is a member of the tetraspanin family that is implicated as a promoter of pathological or physiological angiogenesis. C-Met is expressed on a variety of cells including vascular endothelial cells (VECs) and up-regulated during angiogenesis. In this study, we investigated whether CD151 regulated migration, proliferation, tube formation and angiogenesis of human umbilical VECs (HUVECs) with activation of C-Met. Moreover, we studied whether CD151 could affect the angiogenic molecules such as nitric oxide (NO), vascular cell adhesion molecule-1 (VCAM-1) and vascular endothelial growth factor (VEGF). The expression of CD151 was determined by Western blotting. The cell proliferation assay was performed using the cell counting kit-8 (CCK-8) method and cell migration was assessed in microchemotaxis chambers by using fetal bovine serum (FBS) as the chemotactic stimulus. The angiogenic molecules were evaluated using ELISA. The NO level was detected using NO detection kit. The potential involvement of various signaling pathways was explored using relevant antibodies. We found that proliferation, migration and tube formation of HUVECs were promoted by CD151 with activation of C-Met, FAK and CDC42, while they were suppressed with CD151 knockdown by RNAi. Similarly, the levels of NO, VCAM-1 and VEGF in HUVECs were increased by CD151, but they were inhibited with CD151 knockdown by RNAi. These data suggested that CD151 could promote migration, proliferation, tube formation and angiogenesis of HUVECs, which was possibly related to the C-Met signaling pathways.

In order to clarify the potential role of calcium sensing receptor (CaSR), a typical G protein coupled receptor (GPCR), in hyperglacemia-induced macroangiopathy, experimental hyperglycemia models in vivo and in vitro were prepared. Firstly, SD rats were divided into control group (n=10) and diabetes group (n=10), and diabetic model was induced via high-fat diet feeding and streptozotocin (STZ, 30 mg/kg) injection. Hydroxyproline level, determined via Choramnie T oxidation method, in vessel wall in diabetic rats was 30% more than that in control group. The gene transcription and expression levels were detected by real-time PCR and Western blotting, respectively. Both of collagen I and III mRNA levels in diabetic aorta were nearly twice those in normal aorta. The cleaved caspase-3 and −9 were elevated 1.5 and 2.5 times respectively in diabetic vascular cells. As compared with controls, mRNA and protein levels of CaSR in aorta were increased by 3 and 1.5 times in diabetes group. The expression levels of Bax as well as pro-apoptotic kinases (phospho-p38 and phosphor-JNK) were also increased 2, 0.5 and 0.5 times respectively in diabetic rats. To further validate the involvement of CaSR in cell apoptosis and explore the potential mechanism, the endothelial cell line (human umbilical vascular endothelial cells, HUVECs) was stimulated with high concentration of glucose (33 mmol/L) to mimic hyperglycemia in vitro. Cell-based assays also showed that the CaSR level and key apoptotic proteins (cleaved caspase-3 and −9, Bax, phospho-p38 and phosphor-JNK) were elevated in response to stimulation, and inhibition of CaSR by using specific inhibitor (NPS-2143, 10 μmol/L) could protect cells against apoptosis. Our results demonstrated that CaSR might take important part in the development of diabetic macroangiopathy through promoting cell apoptosis induced by hyperglycemia.

The correlations between the clinicopathological features and the long-term outcomes of renal amyloidosis (RA) were analyzed with a view to develop strategies for improving diagnosis and prognosis of RA. We retrospectively reviewed the clinicopathological characteristics of 47 patients diagnosed with RA between 2004 and 2014 at the Wuhan Union Hospital. The data on the renal histology, clinical manifestations, and prognosis of RA patients were retrieved from the hospital records and characteristic patterns were identified. The histological changes in the kidneys were correlated with the clinical manifestations of RA. Additionally, most RA patients in this study had decreased serum levels of κ light chain and increased urine levels of κ and λ light chains as well as presence of M-protein in the urine and serum. Patients with early RA showed no specific pathognomonic symptoms. Bleeding associated with diagnostic renal biopsy was rare. We recommend that the routine work-up of patients aged over 40 years and presenting with non-diabetic nephropathy includes the non-invasive tests for the measurement of serum and urine levels of κ and λ light chains as well as protein electrophoresis tests for the presence of urinary and serum M-protein. Additionally, such patients should undergo renal biopsy screening with Cong-red staining to ensure early diagnosis of RA and improve their survival, since the risk of hemorrhage related to renal biopsy screening is low at early stages of RA.

The purpose of this study was to observe the expression of LINGO-1 after cerebral ischemia, investigate the effects of retinoic acid (RA) on the expression of LINGO-1 and GAP-43, and the number of synapses, and to emplore the repressive effect of LINGO-1 on neural regeneration after cerebral ischemia. The model of permanent focal cerebral ischemia was established by the modified suture method of middle cerebral artery occlusion (MCAO) in Sprague-Dawley (SD) rats. The expression of LINGO-1 was detected by Western blotting and that of GAP-43 by immunohistochemistry. The number of synapses was observed by transmission electron microscopy. The SD rats were divided into three groups: sham operation (sham) group, cerebral ischemia (CI) group and RA treatment (RA) group. The results showed that the expression level of LINGO-1 at 7th day after MCAO in sham, CI and RA groups was 0.266±0.019, 1.215±0.063 and 0.702±0.081, respectively (P<0.01). The number of Gap-43-positive nerve cells at 7th day after MCAO in sham, CI and RA group was 0, 59.08±1.76 and 76.20±3.12 per high power field, respectively (P<0.05). The number of synapses at 7th day after MCAO was 8.42±0.13, 1.74±0.37 and 5.39±0.26 per μm², respectively (P<0.05). It is concluded that LINGO-1 expression is up-regulated after cerebral ischemia, and RA inhibits the expression of LINGO-1, promotes the expression of GAP-43 and increases the number of synapses. It suggests that LINGO-1 may be involved in the pathogenesis of cerebral ischemia, which may provide an experimenal basis for LINGO-1 antogonist, RA, for the treatment of cerebral ischemia.

The aim of this study was to investigate the possible beneficial effects of Fenofibrate on renal ischemia-reperfusion injury (IRI) in mice and its potential mechanism. IRI was induced by bilateral renal ischemia for 60 min followed by reperfusion for 24 h. Eighteen male C57BL/6 mice were randomly divided into three groups: sham-operated group (sham), IRI+saline group (IRI group), IRI+Fenofibrate (FEN) group. Normal saline or Fenofibrate (3 mg/kg) was intravenously injected 60 min before renal ischemia in IRI group and FEN group, respectively. Blood samples and renal tissues were collected at the end of reperfusion. The renal function, histopathologic changes, and the expression levels of pro-inflammatory cytokines [interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α) and IL-6] in serum and renal tissue homogenate were assessed. Moreover, the effects of Fenofibrate on activating phosphoinositide 3 kinase/protein kinase B (PI3K/Akt) signaling and peroxisome proliferator-activated receptor-α (PPAR-α) were also measured in renal IRI. The results showed that plasma levels of blood urea nitrogen and creatinine, histopathologic scores and the expression levels of TNF-α, IL-8 and IL-6 were significantly lower in FEN group than in IRI group. Moreover, Fenofibrate pretreatment could further induce PI3K/Akt signal pathway and PPAR-α activation following renal IRI. These findings indicated PPAR-α activation by Fenofibrate exerts protective effects on renal IRI in mice by suppressing inflammation via PI3K/Akt activation. Thus, Fenofibrate could be a novel therapeutic alternative in renal IRI.

Systemic lupus erythematosus (SLE) and clear cell renal cell carcinoma (CC-RCC) are serious disorders and usually fatal, and always accompanied with pathological changes in the kidney. Signal-induced proliferation-associated protein 1 (SIPA-1) is a Rap1GTPase activating protein (Rap1GAP) expressed in the normal distal and collecting tubules of the murine kidney. Lupus-like autoimmune disease and leukemia have been observed in SIPA-1 deficient mice, suggesting a pathological relevance of SIPA-1 to SLE and carcinoma in human being. The expression pattern of SIPA-1 is as yet undefined and the pathogenesis of these diseases in humans remains elusive. In this study, we used both immunohistochemistry and quantum dot (QD)-based immunofluorescence staining to investigate the expression of SIPA-1 in renal specimens from SLE and CC-RCC patients. MTT assay and Western blotting were employed to evaluate the effects of SIPA-1 overexpression on the proliferation and apoptosis of renal cell lines. Semi-quantitative reverse transcriptase-PCR (RT-PCR) was applied to examine the changes of hypoxia-inducible factor-1α (HIF-1α) mRNA level. Results showed that SIPA-1 was highly expressed in the proximal and collecting tubules of nephrons in SLE patients compared to normal ones, and similar results were obtained in the specimens of CC-RCC patients. Although SIPA-1 overexpression did not affect cellular proliferation and apoptosis of both human 786-O renal cell carcinoma cells and rat NRK-52E renal epithelial cell lines, RT-PCR results showed that HIF-1α mRNA level was down-regulated by SIPA-1 overexpression in 786-O cells. These findings suggest that SIPA-1 may play critical roles in the pathological changes in kidney, and might provide a new biomarker to aid in the diagnosis of SLE and CC-RCC.

Peritoneal dialysis catheter surgery has been used in clinical treatment for nearly 40 years, and open surgery under local anesthesia is the conventional method. However, catheter displacement after open surgery is still the thorny issue during our clinical practice. Then the reset surgery is often required to be taken again. Nowadays, laparoscopic peritoneal dialysis catheter draws our attention due to its advantages of accurate positioning, smaller incision, and less pain, and its clinical application has been limited. While laparoscopic surgery is recognized, there are few relevant studies on whether there is difference during the catheter reset process between the two surgical approaches. In this study, we mainly discussed the rate of secondary catheter migration, the incidence of complications after catheter reset for two surgical approaches and the hospital stay as well as the total clinical cost for the two surgical approaches. In this study, we retrospectively analyzed 25 cases of end-stage renal disease, who received catheterization for peritoneal dialysis and regular peritoneal dialysis in our hospital from March 2010 to December 2013, and had a medical history of catheter migration. We collected the relevant clinical data for all patients. Fifteen patients selected laparoscopic catheter reset, and 10 patients selected the traditional surgical method for catheter reset by themselves. For all patients enrolled, we analyzed the incidence of secondary catheter migration and postoperative complications, hospitalization time, and total cost for different methods of reset. Through the studies above, we found that laparoscopic peritoneal dialysis catheter surgery offered accurate catheter location and a small incision that was easy to heal. Besides, the incidence of postoperative complications for the laparoscopic surgery was lower than that for traditional surgical approach for catheter reset. The average hospitalization time for laparoscopic surgery was shorter than that for the traditional surgical approach. The total cost of laparoscopic surgery was more than that of the traditional surgery. Therefore, the rational application of a laparoscopic peritoneal dialysis catheter and reset surgery can increase the success rate of peritoneal dialysis, reduce the complications, shorten hospitalization time of patients, and thus enhance patient’s confidence to stick it out.

This study investigated the protective effect of ATP on skeletal muscle satellite cells damaged by H₂O₂ in neonatal rats and the possible mechanism. The skeletal muscle satellite cells were randomly divided into four groups: normal group, model group (cells treated with 0.1 mmol/L H₂O₂ for 50 s), protection group (cells treated with 16, 8, 4, 2, 1, 0.5, or 0.25 mmol/L ATP for 24 h, and then with 0.1 mmol/L H₂O₂ for 50 s), proliferation group (cells treated with 16, 8, 4, 2, 1, 0.5, or 0.25 mmol/L ATP for 24 h). MTT assay, FITC+PI+DAPI fluorescent staining, Giemsa staining and immunofluorescence were performed to examine cell viability and apoptosis, and apoptosis-related proteins. The results showed that the survival rate of skeletal muscle satellite cells was decreased and the apoptosis rate was increased after H₂O₂ treatment (P<0.01). Different doses of ATP had different effects on skeletal muscle satellite cells damaged by H₂O₂: the survival rate of muscle satellite cells treated with ATP at 4, 2, or 1 mmol/L was increased. The protective effect was most profound on cells treated with 2 mmol/L ATP. Immunofluorescence showed that ATP could increase the number of Bcl-2-positive cells (P<0.01) and decrease the number of the Bax-positive cells (P<0.01). It was concluded that ATP could protect skeletal muscle satellite cells against H₂O₂ damage in neonatal rats, which may be attributed to the up-regulation of the expression of Bcl-2 and down-regulation of Bax, resulting in the suppression of apoptosis.

Formaldehyde (FA) is a ubiquitous toxic organic compound, and it has been regarded as a leukemogen. However, the mechanisms by which FA induces bone marrow toxicity remain unclear. The present study was aimed to examine the bone marrow toxicity caused by FA and the mechanism involving the expression changes of peroxiredoxin3 (Prx3) in this process. The mice were divided into four groups with 6 mice per group. Animals in the control group were exposed to ambient air and those in the FA groups to different concentrations of FA (20, 40, 80 mg/m³) for 15 days in the separate inhalation chambers, 2 h a day. At the end of the 15-day experimental period, all mice were killed. Bone marrow cells were obtained. The level of hydrogen peroxide (H₂O₂), the apoptosis rate, and the activities and protein expression levels of caspase-3 and caspase-9 were determined by biochemical assay, flow cytometry and immunohistochemistry, respectively; DNA damage and Prx3 expression levels were measured by single cell gel eletrophoresis immunohistochemistry and Western blotting, respectively. The results showed that the H₂O₂ level and cell apoptosis rate were significantly increased in FA groups relative to the control group. Caspase-3 and caspase-9 activities and their protein expression levels were markedly increased as well. Additionally, FA also increased the rate of DNA damage and the expression level of Prx3 compared with control group. Our study suggested that a certain concentration of FA causes the bone marrow toxicity by regulating the expression of Prx3.

Patients with acute-on-chronic hepatitis B liver failure (HBV-ACLF) show high morbidity and mortality. Independent prognostic predictors of short-term HBV-ACLF mortality include the Child-Turcotte-Pugh (CTP) score, the model for end-stage liver disease (MELD) score, other MELD-based indices and the dynamic changes in these indices. The aims of this study were to evaluate the existing prognostic scores in a large cohort of HBV-ACLF patients and create a new predictive model. We retrospectively reviewed 392 HBV-ACLF patients from December 2008 to November 2011 and evaluated their 3-month survival. The predictive accuracy of CTP, MELD and MELD-based indices and the dynamic changes in the MELD-related scores (Δ scoring systems) upon admission and after two weeks of treatment were compared using the area under the receiver operating characteristic (ROC) curve method. Life-threatening factors and a series of bio-clinical parameters were studied by univariate and multivariate analyses. Among the existing scores, MELD had the best predictive ability. However, our new regression model provided an area under the curve of 0.930±0.0161 (95% CI: 0.869 to 0.943), which was significantly larger than that obtained with the MELD score at admission and after two weeks of treatment as well as with the dynamic changes of the MELD score (0.819, 0.921, and 0.826, respectively) (Z=3.542, P=0.0004). In a large cohort of patients retrospectively reviewed for this study, our prognostic model was superior to the MELD score and is, therefore, a promising predictor of short-term survival in patients with HBV-ACLF.

The effect of high frequency oscillatory ventilation (HFOV) at early stage on hemodynamic parameters, extravascular lung water (EVLW), lung capillary permeability, CC16 and sICAM-1 in piglets with pulmonary or extrapulmonary acute respiratory distress syndrome (ARDS) was explored. Central vein pressure (CVP) and pulse indicator continuous cardiac output (PiCCO) were monitored in 12 anesthetized and intubated healthy piglets. Pulmonary ARDS (ARDSp) and extrapulmonary ARDS (ARDSexp) models were respectively established by lung lavage of saline solution and intravenous injection of oleic acid. Then the piglets received HFOV for 4 h. EVLW index (EVLWI), EVLW/intratroracic blood volume (ITBV) and pulmonary vascular permeability index (PVPI) were measured before and after modeling (T0 and T1), and T2 (1 h), T3 (2 h), T4 (3 h) and T5 (4 h) after HFOV. CC16 and sICAM-1 were also detected at T1 and T5. Results showed at T1, T3, T4 and T5, EVLWI was increased more significantly in ARDSp group than in ARDSexp group (P<0.05). The EVLWI in ARDSp group was increased at T1 (P=0.008), and sustained continuously within 2 h (P=0.679, P=0.216), but decreased at T4 (P=0.007) and T5 (P=0.037). The EVLWI in ARDSexp group was also increased at T1 (P=0.003), but significantly decreased at T3 (P=0.002) and T4 (P=0.019). PVPI was increased after modeling in both two groups (P=0.004, P=0.012), but there was no significant change within 4 h (T5) under HFOV in ARDSp group, while PVPI showed the increasing trends at first, then decreased in ARDSexp group after HFOV. The changes of EVLW/ITBV were similar to those of PVPI. No significant differences were found in ΔEVLWI (P=0.13), ΔPVPI (P=0.28) and ΔEVLW/ITBV between the two groups (P=0.63). The significant decreases in both CC16 and sICAM-1 were found in both two groups 4 h after HFOV, but there was no significant difference between the two groups. It was concluded that EVLWI and lung capillary permeability were markedly increased in ARDSp and ARDSexp groups. EVLW could be decreased 4 h after the HFOV treatment. HFOV, EVLW/ITBV and PVPI were increased slightly at first, and then decreased in ARDSexp group, while in ARDSp group no significant difference was found after modeling. No significant differences were found in the decreases in EVLW and lung capillary permeability 4 h after HFOV.

This study was aimed to explore prevention and treatment of hemorrhage during laparoscopic splenectomy plus devascularization (LSD) for portal hypertension by modified and simplified operation. From June 2012 to June 2014, LSD was performed on 138 patients with portal hypertension. The patients were allocated into two groups: earlier stage (ES) group, in which 45 patients received traditional LSD from June 2012 to Sep. 2012; later stage (LS) group, in which 93 patients underwent modified LSD from Jan. 2013 to June 2014. Perioperative variables were compared between the two groups. Laparoscopic operations were successfully performed in all but two patients in ES group who were converted to laparotomy (total conversion rate: 1.4%). There was no perioperative death or reoperation, and all patients recovered and were discharged from hospital with no serious complications in the six months of postoperative follow-up. The average time in the ES group was longer than that in the LS group (335.1 min vs. 201.3 min, P<0.05). LS group outperformed ES group in terms of blood loss (705.4 mL vs. 910.4 mL, P<0.05). The average operation time to oral diet intake after surgery (40.5 h vs. 50.3 h, P<0.05) and postoperative hospital stay (7.4 d vs. 9.0 days, P<0.05) were much less in the LS group than in the ES group. The overall complication rate (4.3 % vs. 11.1 %, P<0.05) and conversion rate (0% vs. 4.4%, P<0.05) were lower in the LS group than in the ES group. It was concluded that prevention and treatment of hemorrhage are the key points of LSD for portal hypertension. By creating a tunnel above the splenic pedicle and a tunnel behind the lower esophagus, the simplified and modified LSD can reduce hemorrhage and improve success of surgery dramatically, and splenomegaly and severe varices are not contraindications.

Central neurocytomas (CNs), initially asymptomatic, sometimes become huge before detection. We described and analyzed the clinical, radiological, operational and outcome data of 13 cases of huge intraventricular CNs, and discussed the treatment strategies in this study. All huge CNs (n=13) in our study were located in bilateral lateral ventricle with diameter ≥5.0 cm and had a broad-based attachment to at least one side of the ventricle wall. All patients received craniotomy to remove the tumor through transcallosal or transcortical approach and CNs were of typical histologic and immunohistochemical features. Adjuvant therapies including conventional radiation therapy (RT) or gamma knife radiosurgery (GKRS) were also performed postoperatively. Transcallosal and transcortical approaches were used in 8 and 5 patients, respectively. Two patients died within one month after operation and 3 patients with gross total resection (GTR) were additionally given a decompressive craniectomy (DC) and/or ventriculoperitoneal shunt (VPS) as the salvage therapy. Six patients received GTR(+RT) and 7 patients received subtotal resection (STR)(+GKRS). Eight patients suffered serious complications such as hydrocephalus, paralysis and seizure after operation, and patients who underwent GTR showed worse functional outcome [less Karnofsky performance scale (KPS) scores] than those having STR(+GKRS) during the follow-up period. The clinical outcome of huge CNs seemed not to be favorable as that described in previous reports. Surgical resection for huge CNs should be meticulously considered to guarantee the maximum safety. Better results were achieved in STR(+GKRS) compared with GTR(+RT) for huge CNs, suggesting that STR(+GKRS) may be a better treatment choice. The recurrent or residual tumor can be treated with GKRS effectively.

The lentivirus-mediated uPA interference in the proliferation, apoptosis, and secretion of osteoarthritic chondrocytes was examined in this study. Cells were obtained from the cartilage tissues of New Zealand white rabbits. They were cultured with interleukin (IL)-1β (10 ng/mL) for 24 h and then divided into three groups: uPA-siRNA group (cells transfected with uPA-siRNA lentiviruses), blank control group (untreated cells), and negative control group (cells transfected with empty vectors). Western blotting and real-time quantitative reverse transcription-PCR (RT-QPCR) were performed to detect the protein and mRNA expression levels of uPA, MMP-1, MMP-3, MMP-9, MMP-10, MMP-13 and MMP-14 in osteoarthritic chondrocytes. Cell Counting Kit-8, flow cytometry, and colony formation assay were used to examine the proliferation and apoptosis of chondrocytes. The results showed that after uPA-siRNA transfection, the protein and mRNA expression levels of uPA, MMP-1, MMP-3, MMP-9, MMP-10, MMP-13, and MMP-14 were significantly decreased (P<0.05 for MMP-1, MMP-9, MMP-10 and MMP-14, P<0.01 for uPA, MMP-3 and MMP-13). Cell proliferation and colony formation rate were significantly higher and the cell apoptosis rate was significantly lower in uPA-siRNA group than in control groups (P<0.01). The proportion of cells in G₀/G₁ phase was markedly increased and that in the S phase decreased, and the cell cycle was arrested at the G₁/S phase in the control group. In the uPA-siRNA group, the proportion of cells in the S phase was significantly increased, resulting in a different proportion of cells in cell cycle phase (P<0.01). It was suggested that the down-regulation of uPA gene could inhibit the expression of MMPs protein and cell apoptosis, increase the proliferation and colony formation of osteoarthritic chondrocytes.

Glutamate (Glu) is the major afferent excitatory neurotransmitter in the auditory system, and excessive Glu may play an important role in cochlear dysfunction. It is unclear how excessive Glu plays roles in cochlear dysfunction in cochlear organotypic cultures. In this study neonatal rat cochlear organotypic cultures were prepared, and then the cochlear tissues were incubated with a new medium containing specific concentrations of Glu (0.1, 0.5, 1, 10 or 20 mmol/L) for 24 h, or incubated with the medium containing a concentration of 20 mmol/L Glu for 6, 12, 24 or 72 h, respectively. It was found that when the cochlear tissues were cultured for 24 h, the inner hair cells (IHCs) were damaged at the concentration of 0.5 mmol/L Glu, and with the increases of the concentrations, the injury was gradually aggravated, and 20 mmol/L Glu resulted in the significant loss of IHCs. In the 20 mmol/L Glu groups, the stereocilia bundles were missing or disarrayed on a few IHCs after culture for 6 h and the damage effect was time-dependent. The missing of IHCs was more significant in the basal turn of the cochlea than in the middle turn of the cochlea under the same concentration of Glu exposure. These results suggest that excessive exogenous Glu affects the morphology of IHCs, but not affects the outer hair cells (OHCs) in cochlear organotypic cultures, and the excitotoxic effects are different on IHCs of different parts of the cochlea under the same concentration of Glu exposure.

This study investigated the expression of lung surfactant proteins SP-B and SP-C, and their modulating factors TTF-1 and PLAGL2 in the fetal lung of rats with fetal growth restriction (FGR). The rat FGR model was established by prenatal hypoxia in the first stage of pregnancy, 180 rats for experiment served as hypoxia group, and 197 healthy rats served as normal control group. The FGR incidence in hypoxia was compared with that in normal control group. The histological changes in the fetal lung were observed under the light microscope and electronic microscope in two groups. The SP-B, SP-C, TTF-1 and PLAGL2 proteins were determined in the fetal lung of two groups immunohistochemically. The expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and mRNA in the fetal lung of two groups were detected by using Western blotting and RT-PCR respectively. The FGR rat model was successfully established by using hypoxia. Pathologically the fetal lung developed slowly, and the expression levels of SP-B, SP-C, TTF-1 and PLAGL2 protein and mRNA in the fetal lung were significantly reduced in hypoxia group as compared with those in normal control group. It was suggested that maternal hypoxia in the first stage of pregnancy could induce FGR, and reduce the expression of SP-B and SP-C, resulting in the disorder of fetal lung development and maturation.

Severe liver dysfunction in pregnancy (SLDP) is rare but serious complications with high mortality rate. This study compared the effectiveness and safety of double-balloon catheter versus intra-amniotic injection of ethacridine lactate for the termination of second trimester pregnancy in patients with SLD. A total of 55 patients with indications of labor induction were enrolled and analyzed by retrospective control analysis method. Twenty-three cases adopted Cook double balloon dilation as Cook group, and 32 cases received intra-amniotic injection of ethacridine lactate as EL group. The primary outcome was evaluated by successful abortion rate and the difference in the induction-to-abortion interval. Secondary outcomes included liver function recovery and the frequency of adverse events. Both Cook and EL regimens were effective, with successful abortion rate of 87.0% and 93.8%, respectively (P=0.639). The induction-to-delivery interval was similar between Cook group and EL group (38.1±21.5 vs. 41.3±17.4, P=0.543). The liver disease status was more severe in Cook group than in EL group, but it did not show any significant difference after pregnancy termination between the two groups and the improvement rate also did not show any significant difference. Both treatments were safe and there was no significant difference in bleeding and cervical laceration adverse events between the two groups. Our study firstly compared double-balloon catheter and ethacridine lactate for the induction of labor in women with SLD during second trimester pregnancy.

The effects of the balance changes of pigment epithelium growth factor (PEDF) and vascular endothelial growth factor (VEGF) in whole-body and retinal tissue on rats with oxygen-induced retinopathy were investigated. Forty-eight neonatal SD rats at the age of 7 days were randomly divided into 4 groups. The neonatal rats in experimental groups were exposed to 75% to 80% oxygen for 5 days and then to normal air, and those in control groups were kept feeding in normal air. At the age of 17 and 22 days, all the neonatal rats received retina angiography with FITC-dextran and the pathological changes of retinal vessels and perfusion were observed. HE staining of the tissue section and the number counting of endothelial cells extending beyond the inner limiting membrane were performed to evaluate the endothelial proliferation. Immunohistochemistry was applied to detect the expression of PEDF and VEGF in retinal tissue, and ELISA to detect their expression in serum. A hypoxic-ischemic proliferation of retina and more endothelial cells extending beyond the inner limiting membrane were found in the neonatal rats in both experimental groups of 17-day old and 22-day old as compared with those in control group with the difference being statistically significant (P<0.01). VEGF staining of the rats in the 17-day old experimental group was significantly stronger, with an increasing positive rate, than that of the rats in the 17-day old control group (P<0.01). PEDF staining of the rats of 22 days old was weaker than that of the rats of 17 days old in the experimental groups (P<0.01). There was no significant difference in serum VEGF concentration among all groups (P>0.05). The serum PEDF concentration in the rats of 17 days old in experimental group was decreased significantly as compared with that in the rats of 17 days old in control group (P<0.01), and in experimental groups, the serum PEDF concentration of the rats of 22 days old was increased as compared with that of the rats of 17 days old (P<0.01). In conclusion, the obviously decreased serum PEDF concentration and the abnormal enhanced expression of VEGF density in local retinal tissue broke down the balance of PEDF/VEGF in whole-body or local tissues, which might play an important role in retinal vascular proliferation.

China bears a large burden of global maternal mortality, and the largest burden of maternal deaths in China is in poor western provinces. This study aimed to investigate the trends in maternal mortality and its associated factors in Guizhou province of western China between 1996 and 2009, and examine differences between minority and non-minority counties. A population-based, longitudinal, retrospective study was performed in a poor western province of China with a considerably large ethnic minority population. All 86 counties/districts of Guizhou were included with population at county, township and village level. Maternal mortality data were collected from routine reporting database of Guizhou Provincial Health Bureau. Trend and comparative analyses and multivariate linear regression analyses were performed using SPSS 17.0. Maternal mortality ratio (MMR) and its change over time, differences between ethnic groups were analyzed. A declining trend in maternal mortality and rising trend in hospital delivery in Guizhou was observed; ethnic differences between two ethnic groups persisted. The reduction in maternal mortality between 1996 and 2009 was related with increased gross domestic product, decreased male illiteracy rate, and increased hospital delivery rate. We found the declining trends in maternal mortality in Guizhou with persisting ethnic differences. The declining trends are related with economic development, hospital delivery and male illiteracy. Effective health education on maternal health is urgently needed for the minority groups, and basic education for the new generation should be enhanced to eradicate the illiteracy.