Diabetes mellitus is a metabolic disorder syndrome caused by various pathogenic factors leading to imbalance of active substance secretion and endothelial dysfunction, causing macro and micro ...vascular complications. As the most important signal transduction molecule released by endothelium, NO participates in various physiological processes of microcirculation and plays an important role in vascular relaxation regulation. Extensive studies focus on the investigation of the analysis of NO transport in microvessels, RBC motion and its influence on NO transport since they are of extremely importance for understanding the mechanisms of vessel autoregulation and microcirculation lesion. NO transport characteristics are closely associated with hemorheology, hemodynamics and microvascular structure. Nevertheless, up to date, there are limited reports on NO transport characteristics in diabetic mellitus. The purpose of this review is to summarize the current advances in the investigation of NO transport characteristics from cellular to vascular level, which can provide effective ideas for the early diagnosis of vascular complications in diabetes.
•NO is an important vasodilator factor, which can help for assessment of microcirculation dysfunction of type 2 diabetic mellitus.•The paper reviews the modeling work of NO transport in microvessels, RBC movement and its influence on NO transport.•Experimental methodologies targeting measurements of NO concentration are briefly introduced.•The advancements of the modeling and experimental work of NO transport in diabetic mellitus in our group are introduced.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
GATA3 immunostaining is a sensitive marker for mammary and urothelial carcinomas. It is routinely used in surgical pathology during workup of carcinomas of unknown origin. To the best of our ...knowledge, this is the first focused study of GATA3 expression in gallbladder adenocarcinomas. In this study, we evaluated GATA3 expression in 38 gallbladder adenocarcinomas. Eight of 38 (21%) gallbladder adenocarcinomas were positive for GATA3. The expression of GATA3 tended to be moderate to strong when present. It was patchy (<50% positivity) in 4 cases, characterized by discrete clusters or groups of malignant cells with areas of intervening negative tumor cells, whereas it was diffuse (>50% positivity) in the other 4 cases. GATA3 expression did not show any significant correlation with clinicopathologic features such as sex, histologic grade, perineural invasion, vascular invasion, pathologic stage, or distance metastasis. The results of our study show that a subset of gallbladder adenocarcinomas (21%) can be GATA3 positive. Awareness of this phenomenon is important while working up GATA3-positive carcinomas immunohistochemically.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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Hyperoside, an active flavonoid glycoside isolated from many traditional Chinese medicines, has received much attention because of its potential role in osteoporosis treatment. In the ...present study, we investigated the antiosteoporotic role and mechanism of hyperoside on ovariectomized (OVX) mice. Sixty female Kunming mice received one of three treatments orally for 12 weeks: estradiol valerate (0.3 mg/kg body weight/day), hyperoside (20, 40, or 80 mg/kg body weight/day), or vehicle. We found that hyperoside was effective in preventing osteoporosis by increasing bone mineral density, restoring trabecular bone micro-architecture, and enhancing bone strength. Meanwhile, the activities of bone resorption markers, including tartrate-resistant acid phosphatase 5b (TRAP-5b) and C-terminal telopeptide of type I collagen (CTX), were significantly decreased, while the bioactivity of bone formation markers, osteocalcin (OC) and bone-specific alkaline phosphatase (BALP), were significantly increased. Mechanistically, hyperoside reduced the expression of receptor activator of nuclear factor-κB ligand (RANKL), TNF-receptor-associated factor 6 (TRAF6), phosphorylated inhibitor of nuclear factor-κB α (IκBα), NF-kB p65, and nuclear factor of activated T cell cytoplasmic 1 (NFATc1) and promoted the expression of osteoprotegerin (OPG). Therefore, the function of hyperoside might be related to the inhibition of the TRAF-6 mediated RANKL/RANK/NF-κB signaling pathway and the elevation of the OPG/RANKL ratio. These data demonstrated that hyperoside has potential applications as a drug for osteoporosis treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
OBJECTIVE:The purpose was to determine whether obesity surgery is associated with a long-term increased risk of colorectal cancer.
BACKGROUND:Long-term cancer risk after obesity surgery is not well ...characterized. Preliminary epidemiological observations and human tissue biomarker studies recently suggested an increased risk of colorectal cancer after obesity surgery.
METHODS:A nationwide retrospective register-based cohort study in Sweden was conducted in 1980–2009. The long-term risk of colorectal cancer in patients who underwent obesity surgery, and in an obese no surgery cohort, was compared with that of the age-, sex- and calendar year-matched general background population between 1980 and 2009. Obese individuals were stratified into an obesity surgery cohort and an obese no surgery cohort. The standardized incidence ratio (SIR), with 95% confidence interval (CI), was calculated.
RESULTS:Of 77,111 obese patients, 15,095 constituted the obesity surgery cohort and 62,016 constituted the obese no surgery cohort. In the obesity surgery cohort, we observed 70 patients with colorectal cancer, rendering an overall SIR of 1.60 (95% CI 1.25–2.02). The SIR for colorectal cancer increased with length of time after surgery, with a SIR of 2.00 (95% CI 1.48–2.64) after 10 years or more. In contrast, the overall SIR in the obese no surgery cohort (containing 373 colorectal cancers) was 1.26 (95% CI 1.14–1.40) and remained stable with increasing follow-up time.
CONCLUSIONS:Obesity surgery seems to be associated with an increased risk of colorectal cancer over time. These findings would prompt evaluation of colonoscopy surveillance for the increasingly large population who undergo obesity surgery.
Diabetes is frequently associated with structural and functional impairment of the microcirculation. Blood perfusion is an important indicator of both physiological and pathological conditions of the ...microcirculation. Given that temperature is closely related to blood perfusion and is more easily measured, blood perfusion can be estimated from variations in skin temperature using an inverse method.
The aim of this paper was to develop a thermal analysis method for estimation of blood perfusion and apply it in the assessment of skin blood perfusion in diabetic rats. First, diabetes was induced in the rat models of the experimental group. Skin temperature from the rats left hind paws was measured during a 10-min local heating period followed by a 15-min cooling period. A simple one-dimensional heat transfer model, including an arteriolar vessel node, was used to describe the skin heat transfer process. The blood perfusion of the arteriole was estimated by correlating the calculated skin temperature with known experimental temperatures using a genetic algorithm. The results indicated that the average blood perfusion in the control group was higher during local heating and decreased faster during the cooling period, showing dynamic responses to the thermal stimuli. In contrast, the blood perfusion of diabetic rats was reduced compared with that of the control rats during the heating phase and the rate of decrease in perfusion during the cooling stage was similarly reduced, implying a slower response to thermal stimulation in these rats. It is interesting to note that diabetic rats fed a normal diet showed a similar blood perfusion pattern to that in the control rats, implying that diet may be important in the treatment of diabetes-associated microvascular dysfunction.
•The variations of the skin blood perfusion rates during and after heating were estimated using a genetic algorithm.•The blood perfusion rates of normal rats are considerably large during heating and they decrease promptly after power off.•The blood perfusion rates of some diabetic rats in the heating stage are significantly lower than those of normal rats.•The ratio of power-off-phase to power-on-phase blood perfusion rates of some diabetic rats is higher.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In this paper, we analyze the 180 stocks which have the potential influence on the Shanghai Stock Exchange (SSE). First, we use the stock closing prices from January 1, 2005 to June 19, 2015 to ...calculate logarithmic the correlation coefficient and then build the stock market model by threshold method. Secondly, according to different networks under different thresholds, we find out the potential influence stocks on the basis of local structural centrality. Finally, by comparing the accuracy of similarity index of the local information and path in the link prediction method, we demonstrate that there are best similarity index to predict the probability for nodes connection in the different stock networks.
OBJECTIVE:To compare key outcomes after transcatheter arterial embolization (TAE) with conventional surgery for peptic ulcer bleeding when endoscopic intervention fails to achieve hemostasis.
...BACKGROUND:Mortality in peptic ulcer bleeding remains high, especially in patients who require surgical treatment.
METHODS:A population-based cohort study in Stockholm, Sweden, in 2000 to 2014, assessing the main outcome all-cause mortality and the secondary outcomes re-bleeding, re-intervention, length of hospitalization, and complications, was conducted. Data were taken from well-maintained registries and medical records. Multivariable Cox-regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, ulcer history, comorbidity, and calendar period were considered.
RESULTS:Included were 282 patients, 97 in the TAE group and 185 in the surgery group. Compared with the surgery group, the overall hazard of death was 34% decreased in the TAE group (adjusted HR 0.66, 95% CI 0.46–0.96). The corresponding HRs for mortality within 30 days, 90 days, 1 year, and 5 years were 0.70 (95% CI 0.37–1.35), 0.69 (95% CI 0.38–1.26), 0.88 (95% CI 0.53–1.47), and 0.67 (95% CI 0.45–1.00), respectively. The risk of re-bleeding was higher after TAE compared with surgery (HR 2.48, 95% CI 1.33–4.62). The median length of hospital stay was shorter in the TAE group—8 versus 16 days—acceleration factor 0.59 (95% CI 0.45–0.77) and the risk of complications was lower (8.3% vs 32.2%; P < 0.0001).
CONCLUSIONS:This study indicates that TAE compares favorably with surgery regarding prognosis after refractory peptic ulcer bleeding, and the shorter length of hospital stay and fewer complications outweigh a higher risk of re-bleeding. TAE could be recommended as first-line treatment for these patients.
A diabetogenic high fat diet (HFD) can be used to induce insulin resistance and obesity in animal models; however, its effects on bone are unknown. We investigated the effects of long term HFD on ...bone in ovariectomized (OVX) female rats. We used 12-week-old female rats divided randomly into four groups: sham operation (sham), sham operation with HFD (SHFD), OVX and OVX with HFD (OVX + HFD). Ovaries were removed in the OVX and OVX + HFD groups and the SHFD and OVX + HFD groups were fed a HFD for 28 weeks. Serum estrogen, testosterone, lipid, adiponectin, leptin, tartrate-resistant acid phosphatase (TRAP) and N-mid fragment of osteocalcin (N-MID-OT) levels were measured. Structure, apoptosis and specific transcription factors in bone were evaluated using pathologic, densitometric and immunohistochemical analysis. Body weight, serum leptin, TRAP and testosterone levels were increased, while serum N-MID-OT, estrogen and adiponectin levels were decreased in the SHFD, OVX and OVX + HFD groups. Expression of BCL2-associated X protein, caspase-3, matrix metalloproteinase-9 and calcitonin was increased, while bone mineral density (BMD) and content (BMC) in femurs and lumbar spine, and expression of B cell lymphoma 2, type 1 collagen and osteocalcin were decreased in the bones of the SHFD, OVX and OVX + HFD groups. All indices were greatest in the OVX + HFD group and HFD produced a detrimental effect on bone in both normal and OVX rats, which may be due to increased apoptosis in bone and increased leptin and decreased adiponectin levels in serum. The effects of HFD and OVX may be synergistic.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Obesity is associated with hypertriglyceridemia and elevated circulating free fatty acids (FFA), resulting in endothelial dysfunction. Endoplasmic reticulum (ER) stress has been implicated in many of ...these processes. To determine if ER stress participates in palmitate-induced apoptosis, we investigated the effects of diet-induced obesity and palmitate on mouse aortic endothelial cells (MAEC) in vivo and in vitro.
Male C57BL/6 mice were fed standard chow diets (SCD) or high-calorie and high-cholesterol diets (HCD) for 3months. Insulin resistance was detected, and the serum, including proinflammatory indices and markers of endothelial function, was also analyzed. The ultrastructure and apoptosis of the endothelial cells in the thoracic aorta were observed. The primary MAEC were separated and treated with palmitate at different concentrations or different times respectively to observe any changes in cellular proliferation, intracellular reactive oxygen species (ROS) levels and apoptosis. Finally, the ER stress markers C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) were analyzed.
HCD-fed obese mice became inflammation-activated and insulin-resistant. Swollen mitochondria, expanded ER and apoptosis in the endothelial cells of the thoracic aorta were observed in HCD-fed mice. Palmitate inhibited cell proliferation, increased production of ROS and induced apoptosis in MAEC. CHOP was overexpressed and shifted into the nucleus (mainly), while the expression of GRP78 was upregulated in the palmitate-treated MAEC.
Our results indicate that diet-induced obesity results in endothelial dysfunction in vivo, and that oxidative and ER stress may be involved in apoptosis induced by the palmitate in vitro.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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Danzhi jiangtang capsule (DJC) is mainly used to treat type 2 diabetes mellitus and vascular complication. Our aim was to investigate whether the protective effects of DJC by oral ...administration on high-fat diet (HFD) and palmitic acid-induced damages of endothelial cells are related to oxidative stress and endoplasmic reticulum (ER) stress. Male Sprague-Dawley rats were randomly divided into standard chow diet (SCD), HFD, HFD plus DJC-low dose (HFD + DJCL) and HFD plus DJC-high dose treatment groups (HFD + DJCH). The latter three groups were given HFD feeding for three months, then the HFD + DJCL and HFD + DJCH rats were treated with DJC (500 and 1000 mg/kg/day) via gavage for another two months respectively. Endothelium-dependent relaxations induced by acetylcholine were observed in isolated rat thoracic aortic ring preparation. Malondialdehyde (MDA), total-antioxidant capacity (T-AOC), superoxide dismutase (SOD), interleukin 1β (IL-1β), tumour necrosis factor α (TNFα), free fatty acids (FFA), endothelin-1 (ET-1) and nitric oxide (NO) levels in serum were assayed. The pathological changes, protein expression of endothelial NO synthase (eNOS), phosphorylated eNOS (p-eNOS) and ER stress-related genes in the thoracic aorta were measured. Human umbilical vein endothelial cells (HUVEC) were treated with serum-medicated DJC and then with palmitic acid to detect the reactive oxygen species (ROS) levels and C/EBP homologous protein (CHOP) distribution, expression of p-eNOS and ER stress-related genes. DJC therapy exhibited a potent antioxidant activity and effectively prevented the endothelial dysfunction (ED) manifested by promoting p-eNOS expression and enhancing NO release, decreasing lipid deposition (Oil-red O staining, CPT1b and ACC) and inflammation (IL-1β, TNFα, CD68 and p-JNK), alleviating oxidative and ER stress, and decreasing the apoptosis of endothelial cells (TUNEL, BCL-2 and BAX) induced by HFD and palmitic acid respectively. These findings suggest that the administration of DJC had endothelial protective effects against HFD-induced ED, inflammation and apoptosis by alleviating lipid deposition, oxidative and ER stress.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP