Ghrelin improves cognition via activation of the cAMP- CREB signalling pathway in depressed male C57BL/6J mice.

BACKGROUND: Depression leads to a cognitive decline and decreases in ghrelin are observed in depression. Ghrelin affects the level of Brain-derived nerve growth factor (BDNF) through the cAMP-CREB signalling pathway, and lower BDNF levels lead to cognitive decline. Therefore, it is reasonable to assume that in depression, lower ghrelin causes a decrease in BDNF levels and cognitive decline though the cAMP- CREB signalling pathway. METHODS: A total of 120 C57BL/6J male mice were randomly divided into six groups of 20 mice: non-depression groups (sham group, ghrelin group, and ghrelin + (D-lys3)-GHRP-6 group) and depression groups (depression group, depression + ghrelin group and depression + ghrelin + (D-lys3)-GHRP group). A depression mouse model was established by injecting normal saline, ghrelin or ghrelin + (D-lys3) -GHRP-6 into the lateral ventricle of each group. Cognition, hippocampal long-term potentiation (LTP), ghrelin mRNA and protein level, BDNF level and CREB level in the hippocampus were detected. RESULTS: In the depression mouse model groups, all comparison indexes (cognition and hippocampal levels of LTP, ghrelin mRNA and proteins, and BDNF and CREB) had significant negative changes. In the mice with depression, ghrelin or ghrelin + (D-lys3)-GHRP-6 was injected, and all the comparison indicators showed significant positive changes. Supplementation of ghrelin+(D-lys3))-GHRP-6 resulted in more significant positive changes in all comparison indexes than those of ghrelin alone. CONCLUSIONS: In the depression model, lower ghrelin causes hippocampal BDNF to decrease and results in cognitive decline via the cAMP-CREB signalling pathway.

Effects of fastigial nucleus electrostimulation on cardiac nerve regeneration, neurotransmitter release, and malignant arrhythmia inducibility in a post-infarction rat model.

The reduced density of cardiac autonomic nerves plays an important role in malignant arrhythmia after myocardial infarction (MI). Previous studies have shown that there is an interaction between the brain and the heart, and fastigial nucleus electrostimulation (FNS) promotes central nerve regeneration. Whether and how it can promote cardiac nerve regeneration after MI and the underlying mechanisms remain unknown. This study investigated whether FNS promotes cardiac nerve regeneration and reduces malignant arrhythmia inducibility in a post-infarction rat model. Ninety-eight Wistar rats were randomly assigned to Sham control, MI (left anterior descending coronary artery ligation without FNS), FNS (MI plus FNS), and FNL (fastigial nucleus lesion plus FNS plus MI) groups. The frequency of malignant arrhythmia was significantly lower in the FNS group than in the MI and FNL groups. The density of cardiac autonomic nerves was less in the MI group than in the Sham group, which was promoted by FNS. The nerve growth factor (NGF) mRNA expression was downregulated in the MI group compared to the Sham group, which was significantly enhanced by FNS. The expression levels of norepinephrine (NE) and acetylcholine (ACh) were higher and lower respectively in the MI and FNL groups than in the Sham group. After FNS, NE concentration was reduced and Ach level was elevated compared to the MI group. These data suggested that FNS promoted the regeneration of cardiac autonomic nerves and reduced the incidence of malignant arrhythmias in MI rat model. The mechanisms might involve up-regulation of NGF mRNA expression, decrease of NE release and increase of ACh release.

Menin Reduces Parvalbumin Expression and is Required for the Anti-Depressant Function of Ketamine.

Dysfunction of parvalbumin (PV) neurons is closely involved in depression, however, the detailed mechanism remains unclear. Based on the previous finding that multiple endocrine neoplasia type 1 (Protein: Menin; Gene: Men1) mutation (G503D) is associated with a higher risk of depression, a Menin-G503D mouse model is generated that exhibits heritable depressive-like phenotypes and increases PV expression in brain. This study generates and screens a serial of neuronal specific Men1 deletion mice, and found that PV interneuron Men1 deletion mice (PcKO) exhibit increased cortical PV levels and depressive-like behaviors. Restoration of Menin, knockdown PV expression or inhibition of PV neuronal activity in PV neurons all can ameliorate the depressive-like behaviors of PcKO mice. This study next found that ketamine stabilizes Menin by inhibiting protein kinase A (PKA) activity, which mediates the anti-depressant function of ketamine. These results demonstrate a critical role for Menin in depression, and prove that Menin is key to the antidepressant function of ketamine.

Depression as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies.

BACKGROUND: This study examined whether depression was a risk factor for onset of dementia including Alzheimer's disease (AD), vascular dementia (VD) and any dementia, and mild cognitive impairment (MCI) by using a quantitative meta-analysis of longitudinal studies. METHODS: EMBASE and MEDLINE were searched for articles published up to February 2011. All studies that examined the relationship between depression and the onset of dementia or MCI were included. Pooled relative risk was calculated using fixed-effects models. RESULTS: Twelve studies met our inclusion criteria for this meta-analysis. All subjects were without dementia or MCI at baseline. Four, two, five, and four studies compared the incidence of AD, VD, any dementia, and MCI between subjects with or without depression, respectively. After pooling all the studies, subjects with depression had higher incidence of AD (relative risk (RR):1.66, 95% confidence interval (CI): 1.29-2.14), VD (RR: 1.89, 95% CI: 1.19-3.01), any dementia (RR: 1.55, 95% CI: 1.31-2.83), and MCI (RR: 1.97, 95% CI: 1.53-2.54) than those without depression. CONCLUSIONS: The quantitative meta-analysis showed that depression was a major risk factor for incidence of dementia (including AD, VD, and any dementia) and MCI.

Circadian rhythm of TSH levels in subjects with Alzheimer's disease (AD).

OBJECTIVES: The circadian rhythm of serum thyroid stimulating hormone (TSH) levels in patients with Alzheimer's disease was measured by means of a case-control study. METHODS: Serum samples from cases and controls were collected continuously for 2 days, and then once every 2 h (even number time-point during the first day and odd number time-point in the second). TSH was detected by radioimmunoassay. RESULTS: AD patients had no significant circadian rhythm in serum TSH levels, whereas normal controls did. In normal controls, serum TSH levels from 19:00 to 20:00 were the lowest (19:00, 3.89 ± 0.97 mIU/L; 20:00, 3.76 ± 0.84 mIU/L) and those in the period 2:00-4:00 were the highest (2:00, 6.15 ± 0.94 mIU/L; 3:00, 6.32 ± 1.04 mIU/L; 4:00, 6.39 ± 1.13 mIU/L; F = 6.762, df = 23, P = 0.002). However, in AD patients, 24-h serum TSH levels were 3.80-4.03 mIU/L (F = 0.897, df = 23, P = 0.996). At the 24 time-points, except for the four time-points from 16:00 to 19:00, TSH levels in AD patients were significantly lower than those in normal controls. CONCLUSIONS: The circadian rhythm of serum TSH levels in AD patients did not appear, and their serum TSH levels were significantly lower than those in normal controls. SIGNIFICANCE: The circadian rhythm in serum TSH levels in AD patients differs greatly from that of the general population.

Protective effect of leukemia inhibitory factor on the retinal injury induced by acute ocular hypertension in rats.

Glaucoma is one of the leading causes of irreversible blindness worldwide. As such, neuroprotective therapy is essential for the treatment of this disease. Leukemia inhibitory factor (LIF) is a member of the IL-6 cytokine family and the LIF signaling pathway is considered to be one of the major endogenous factors mediating neuroprotection in the retina. Therefore, the present study aimed to investigate the possible effects of LIF in acute ocular hypertension (AOH). The intraocular pressure in rat eyes was raised to 110 mmHg for 1 h by infusing the anterior chamber with normal saline to establish the AOH model. In the treatment group, LIF was then injected into the vitreous cavity after AOH was ceased. The retinal tissues were obtained after the termination of AOH, and H&E staining was conducted to assess the morphological damage. The number of retinal ganglion cells (RGCs) was counted using the Fluoro-Gold retrograde staining method. TUNEL staining was used to determine the extent of apoptosis among the retinal cells. In addition, the protein expression levels of cleaved caspase-3, poly (ADP-ribose) polymerase (PARP), STAT3 and components of the AKT/mTOR/70-kDa ribosomal protein S6 kinase (p70S6K) signaling pathway were examined by western blotting. The results showed that AOH induced tissue swelling and structural damage in the retina, which were reversed by LIF injection. In the LIF treatment group, RGC loss was significantly inhibited and the quantity of TUNEL-stained cells was also significantly reduced, whereas the expression of cleaved caspase-3 and PARP was decreased. Furthermore, increased phosphorylation of STAT3, AKT, mTOR and p70S6K was observed after LIF treatment. By contrast, pretreatment with the STAT3 inhibitor C188-9 or the PI3K/AKT/mTOR inhibitor LY3023414 reversed the LIF-induced inhibition of RGC loss. These results suggested that exogenous LIF treatment inhibited the retinal damage induced by AOH, which was associated with the activation of STAT3 and mTOR/p70S6K signaling. Therefore, LIF may serve a role in neuroprotection for glaucoma treatment.

Neuroprotective effect of mesenchymal stem cell-derived extracellular vesicles on optic nerve injury in chronic ocular hypertension.

Mesenchymal stem cells have neuroprotective effects that limit damage to the retina and photoreceptors, and which may be mediated by extracellular vesicles (or exosomes) released by mesenchymal stem cells. To investigate the neuroprotective effect of extracellular vesicles derived from umbilical cord mesenchymal stem cells on glaucoma, we established rat models of chronic ocular hypertension by injecting conjunctival fibroblasts into the anterior chamber to mimic optic nerve injury caused by glaucoma. One week after injury, extracellular vesicles derived from umbilical cord-derived mesenchymal stem cells were injected into the vitreous cavity. We found that extracellular vesicles derived from mesenchymal stem cells substantially reduced retinal damage, increased the number of retinal ganglion cells, and inhibited the activation of caspase-3. These findings suggest that mesenchymal stem cell-derived extracellular vesicles can help alleviate optic nerve injury caused by chronic ocular hypertension, and this effect is achieved by inhibiting cell apoptosis.

Age and risk for depression among the elderly: a meta-analysis of the published literature.

OBJECTIVE: The goal of this study was to determine the relationship between age and risk for depression among the old and the oldest old. Method MEDLINE, EMBASE, and the Cochrane Library database were used to identify potential studies. The studies were divided into cross-sectional and longitudinal subsets. For each study, the numbers of the total participants, cases (for cross-sectional study), or incident cases (for longitudinal study) of depression in each age group were extracted and entered into Review Manager 4.2 software. Qualitative meta-analyses of cross-sectional studies and of longitudinal studies were performed. For prevalence and incidence rates of depression, odds risk (OR) and relative risk (RR) were calculated, respectively. RESULTS: The qualitative meta-analyses showed that, compared with younger participants (above vs. below 65 years, above vs. below 70 years, above vs. below 75 years, and above vs. below 80 years), older age groups had a significantly higher risk for depression. (All of the ORs and RRs were significant.) Compared with participants aged 55-89, those aged above 90 years had no higher risk for depression. (Neither the OR nor the RR was significant.) CONCLUSIONS: Despite the methodological limitations of this meta-analysis, older age appears to be an important risk factor for depression in the general elderly population (aged below 80 years), but not in the oldest population (aged above 85 years).

Association of serum uric acid with Pro12Ala polymorphism in PPAR-γ2 among Chinese nonagenarians/centenarians.

BACKGROUND AND AIMS: In previous studies, Pro12Ala polymorphism in peroxisome proliferator- activated receptors gamma 2 (PPAR-γ2) was shown to be associated with both longevity and metabolic syndrome, which was closely related with hyperuricemia. We examined long-lived subjects (≥90 years), to ascertain whether the polymorphism is associated with the level of serum uric acid (SUA). METHODS: The present study analysed data from a survey conducted in 2005 on all residents aged 90 years or more in a district with 2,311,709 inhabitants. RESULTS: The sample comprised 669 unrelated Chinese participants (aged 90-108 years, mean: 93.54±3.53 years; 67.2% women). The genotype frequencies of the Pro12Ala polymorphism were 0% Ala12Ala and 9.0% Pro12Ala, 91.0% Pro12Pro. Between men or women, and between subjects who were or were not 12Ala carriers, neither in SUA levels nor the prevalence of hyperuricemia were significant. Between subjects with and without hyperuricemia, the difference in prevalence of 12Ala carriers was also non-significant. Unadjusted and adjusted multiple logistic regressions showed that the odds ratios (OR) for hyperuricemia were not associated with Pro12Ala polymorphism in PPAR-γ2. CONCLUSIONS: In Chinese nonagenarians and centenarians, SUA levels are not associated with polymorphism in PPAR-γ2.

A Machine Learning Method for the Quantitative Detection of Adulterated Meat Using a MOS-Based E-Nose.

Meat adulteration is a global problem which undermines market fairness and harms people with allergies or certain religious beliefs. In this study, a novel framework in which a one-dimensional convolutional neural network (1DCNN) serves as a backbone and a random forest regressor (RFR) serves as a regressor, named 1DCNN-RFR, is proposed for the quantitative detection of beef adulterated with pork using electronic nose (E-nose) data. The 1DCNN backbone extracted a sufficient number of features from a multichannel input matrix converted from the raw E-nose data. The RFR improved the regression performance due to its strong prediction ability. The effectiveness of the 1DCNN-RFR framework was verified by comparing it with four other models (support vector regression model (SVR), RFR, backpropagation neural network (BPNN), and 1DCNN). The proposed 1DCNN-RFR framework performed best in the quantitative detection of beef adulterated with pork. This study indicated that the proposed 1DCNN-RFR framework could be used as an effective tool for the quantitative detection of meat adulteration.

The association of nonalcoholic fatty liver disease with bone mineral density in type 2 diabetes.

OBJECTIVE: We examined the association between nonalcoholic fatty liver disease and lumbar spine bone mineral density in individuals with and without type 2 diabetes. METHODS: The lumbar BMD of 1088 subjects was measured using dual-energy X-ray absorptiometry (DXA). Liver fat content was quantified via B-mode ultrasound. Multivariable linear regression was used to study the association between NAFLD and lumbar BMD in participants with and without T2DM. RESULTS: The lumbar BMD in the T2DM group and the non-diabetes group was higher in the NAFLD group than in the non-NAFLD group (P < 0.001). Multivariate regression analysis in the T2DM group showed that after adjusting for confounders, the positive association between lumbar spine BMD and NAFLD remained (P = 0.027). In the non-diabetes group, after adjusting for confounders, the association between NAFLD and lumbar spine BMD disappeared. CONCLUSIONS: The relationship between nonalcoholic fatty liver disease and lumbar bone mineral density may differ in individuals with and without diabetes. The effect of nonalcoholic fatty liver disease on bone mineral density needs to be evaluated in different clinical contexts.

Cognitive function and risk for depression in old age: a meta-analysis of published literature.

BACKGROUND: We assessed the relationship between cognitive impairment (including mild cognitive impairment with no signs of dementia, and dementia) and risk for depression in old age (60 years and older). METHODS: MEDLINE, EMBASE and the Cochrane Library database were used to identify potential studies. All of the clinical studies that produced data on the association between cognitive function and risk of depression among individuals aged 55 years or older were identified and included in this review. The studies were classified into cross-sectional and longitudinal subsets. The quantitative meta-analysis of cross-sectional and longitudinal studies were performed. For prevalence and incidence rates of depression, odds risk (OR) and relative risk (RR) were calculated, respectively. RESULTS: Since all but two studies found in the search were for individuals aged 60 years or over, we assessed and reported on results for this larger group only. In this review we included 13 cross-sectional and four prospective longitudinal studies. The quantitative meta-analysis showed that, in old age, individuals with non-dementia cognitive impairment had neither significant higher prevalence nor incidence rates of depression than those without (odds risk (OR): 1.48, 95% confidence intervals (95% CI): 0.87-2.52; relative risk (RR): 1.12, 95% CI: 0.62-2.01). In old age, individuals with dementia had both significant higher prevalence and incidence rates of depression than those without (OR: 1.82, 95% CI: 1.15-2.89; RR: 3.92, 95% CI: 1.93-7.99). CONCLUSIONS: Despite the methodological limitations of this meta-analysis, we found that in old age, there was no association between depression and cognitive impairment with no dementia; however, there was a definite association between depression and dementia and thus dementia might be a risk for depression.

Human Umbilical Cord-Mesenchymal Stem Cells Survive and Migrate within the Vitreous Cavity and Ameliorate Retinal Damage in a Novel Rat Model of Chronic Glaucoma.

Glaucoma is the leading cause of irreversible blindness worldwide, and pathologically elevated intraocular pressure (IOP) is the major risk factor. Neuroprotection is one of the potential therapies for glaucomatous retinal damage. Intravitreal mesenchymal stem cell (MSC) transplantation provides a viable therapeutic option, and human umbilical cord- (hUC-) MSCs are attractive candidates for cell-based neuroprotection. Here, we investigated the ability of transplanted hUC-MSCs to survive and migrate within the vitreous cavity and their neuroprotective effects on chronic glaucomatous retina. For this, we developed a chronic ocular hypertension (COH) rat model through the intracameral injection of allogeneic Tenon's fibroblasts. Green fluorescent protein-transduced hUC-MSCs were then injected into the vitreous cavity one week after COH induction. Results showed that a moderate IOP elevation lasted for two months. Transplanted hUC-MSCs migrated toward the area of damaged retina, but did not penetrate into the retina. The hUC-MSCs survived for at least eight weeks in the vitreous cavity. Moreover, the hUC-MSCs were efficient at decreasing the loss of retinal ganglion cells; retinal damage was attenuated through the inhibition of apoptosis. In this study, we have developed a novel COH rat model and demonstrated the prolonged neuroprotective potential of intravitreal hUC-MSCs in chronic glaucoma.

Fibrinogen, fibrin degradation products and risk of sarcopenia.

BACKGROUND & AIMS: Increasing data suggests that chronic low-grade inflammation plays an important role on development of sarcopenia. The present study was designed to identify the association between fibrinogen, fibrin degradation products (FDP) and sarcopenia risk in hospitalized old patients. METHODS: A total of 437 patients were enrolled in this cross-sectional study (148 with sarcopenia and 289 without sarcopenia). Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Body composition, grip strength and gait speed were performed to participants. Fibrinogen, FDP levels were measured. Logistic regression analyses were carried out to assess the association between fibrinogen and sarcopenia, between FDP and sarcopenia, respectively. RESULTS: Compared to non-sarcopenic patients, fibrinogen and FDP levels were found to be higher in the sarcopenic group (3.07 g/L vs 2.79 g/L, 1.75 µg/mL vs 1.00 µg/mL, respectively, p < 0.05). Multiple linear regression analysis showed a significant negative association between fibrinogen and gait speed (ß: -0.164, p = 0.008), and muscle strength (ß: -0.231, p < 0.001). Multivariable logistic regression analysis showed that fibrinogen and FDP were independently associated with sarcopenia (odds ratio 1.32 [95% confidence interval 1.03, 1.70], p = 0.009; odds ratio 1.07 [95% confidence interval 1.01, 1.19], p = 0.049, respectively). ROC curve revealed that the cutoff values of fibrinogen and FDP to predict sarcopenia risk were 2.54 g/L and 1.15 µg/mL, respectively. CONCLUSIONS: In hospitalized old patients, serum fibrinogen and FDP levels are elevated in sarcopenia patients than those without sarcopenia. Fibrinogen and FDP are associated with sarcopenia in a concentration-dependent manner.

Association between body mass index and cognitive function among Chinese nonagenarians/centenarians.

AIMS: We examined the individual association between body mass index (BMI) and cognitive function among the very elderly. METHODS: The present study analyzed data from a survey that was conducted on all residents aged 90 years or more from a district which had 2,311,709 inhabitants in 2005. The subjects were divided into 4 groups according to quartiles of BMI (<16.6, 16.6-18.9, 18.9-21.1 and >21.1), and according to classification criteria of underweight, normal weight, overweight and obesity in BMI (<18.5, 18.5-23.0, 23.0-27.5 and >27.5), respectively. RESULTS: The subjects included in the statistical analysis were 211 men and 427 women. Those in the 3rd quartile of BMI (18.9-21.1) had higher cognitive function scores (p < 0.001) and were less likely to present possible dementia (p = 0.016) than the others. However, there was no difference in cognitive function scores (p = 0.350) or prevalence of possible dementia (p = 0.263) among obesity, overweight, normal weight and underweight groups. CONCLUSIONS: Concerning longevity in Chinese, there is an association between BMI and cognitive function. BMI of around 20 (18.9-21.1) is associated with the lowest risk of prevalence of possible dementia and the highest cognitive function scores.

Relationship between anti-fibrotic effect of Panax notoginseng saponins and serum cytokines in rat hepatic fibrosis.

The aim of this study was to investigate the relationship between anti-fibrotic effect of Panax notoginseng saponins (PNS) and serum cytokines in rat hepatic fibrosis. Hepatic fibrosis induced by carbon tetrachloride (CCl(4)) was studied in animal models using SD rats. Liver index, serum alanine amino transferase (ALT), aspartate amino transferase (AST), transforming growth factor-beta1 (TGF-beta1), tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured, respectively. Liver index and the degree of liver fibrosis were also determined. Our results showed that the levels of ALT, AST and liver index in PNS-treated group were markedly lower than those in model group. PNS therapy also significantly attenuated the degree of hepatic fibrosis, collagen area and collagen area percent in liver tissue. Furthermore, the levels of serum TGF-beta1, TNF-alpha and IL-6 were strikingly reduced in PNS-treated group compared with model group while the production of IL-10 was up-regulated. These findings demonstrate that PNS has certain therapeutic effects on hepatic fibrosis probably by immunoregulating the imbalance between pro-fibrotic and anti-fibrotic cytokines.

Association of cognitive impairment with serum lipid/lipoprotein among Chinese nonagenarians and centenarians.

The association of cognitive impairment with abnormal levels of serum lipid/lipoprotein in the elderly, in whom there are differences between the old aged 65-84 years and the oldest old aged 85 years or above, has been confirmed by previous studies. However, there are no relevant data from a Chinese oldest old population. In the present study, we observed an association of cognitive impairment with abnormal levels of serum lipid/lipoprotein among very old people using a Chinese cohort aged 90-108 years. The population included 709 unrelated Chinese nonagenarians and centenarians (67.8% women, mean age 93.8 years). The mean score of cognitive function (measured with the 30-item Mini-Mental State Examination, MMSE) was 14.9 (SD 6.0). Comparing abnormal with normal levels of serum lipid/lipoprotein (including triglycerides, total cholesterol, high-density lipoprotein and low-density lipoprotein), in both genders, the odds ratio of cognitive impairment was statistically insignificant. There were no significant differences in levels of lipid/lipoprotein between subjects with and without cognitive impairment. Pearson correlation showed that MMSE scores were not significantly correlated with levels of lipid/lipoprotein. In summary, we found that levels of serum lipid/lipoprotein were not directly correlated with cognitive impairment among Chinese nonagenarians and centenarians.

Association of cognitive impairment with smoking, alcohol consumption, tea consumption, and exercise among Chinese nonagenarians/centenarians.

PURPOSE: In the present study, we observed the association of cognitive impairment with current/former habits of smoking, alcohol consumption, tea consumption, and exercise among very old people using a Chinese cohort aged 90 to 108 years. METHODS: A cross-sectional study. RESULTS: The sample included 681 unrelated Chinese nonagenarians/centenarians (67.25% women). In men, compared with subjects without cognitive impairment, those with cognitive impairment had significantly higher prevalence of habits of smoking (P=0.048 and 0.004, for former/current, respectively) and alcohol consumption (P=0.003 and 0.049, for former/current, respectively) but had significantly lower prevalence of habits of tea consumption (P=0.041 and 0.044, for former/current, respectively) and current exercise (P=0.020). Subjects with habits of smoking had significantly lower cognitive function scores than those without these habits (mean difference=1.78 and 1.69, P=0.029 and 0.035, for former/current, respectively), but subjects with habit of current exercise had significantly higher cognitive function scores than those without this habit (mean difference=1.53, P=0.038). However, in women, there were no significant differences in prevalence of these habits between subjects with and without cognitive impairment and also no significant differences in cognitive function scores between subjects with and without these habits. Only current smoking habits in men had a significant odds ratio for cognitive impairment (odds ratio, 2.125; 95% confidence interval, 1.186-3.998). CONCLUSIONS: Among nonagenarians/centenarians, in men, there are associations of cognitive impairment with habits of former/current smoking and current exercise, as well as indefinite associations with habits of alcohol and tea consumption. Smoking may have a significant negative impact on cognitive function, but current exercise significantly improve cognitive function. However, in women, there are no associations of cognitive impairment with all the habits.

[Study on the change of myocardial cell and matrix in the rats with insulin resistance and type 2 diabetes mellitus].

OBJECTIVE: To explore the injury of insulin resistance on cardiac muscle cell and matrix, and the relationship between insulin resistance and diabetic cardiomyopathy. METHODS: Twenty four Wistar rats of 6 months were randomly divided into normal control (N), insulin resistance group (I), diabetic group (D). Euglycemic insulin clamp technique (EICT) was used to determine insulin resistance (IR). Cadiocyte apoptosis was evaluated by TUNEL. Heart weight (HW) and body weight (BW) were measured to calculate HW/BW. Ultra-microstructure of cardiac muscle cell and structure of heart was observed. Masson dyeing, hydroxyproline detection and immunohistochemistry were used to measure the levels of collagen protein. RESULTS: Compared with controls, GIR decreased remarkably in D group and I group (P < 0.01). The number of apoptosis cell in I group was lower than that of D group (P < 0.01), and higher than that of N group (P < 0.01). Injury change of ultramicrostructure of myocardial cell was observed in the rats with type 2 diabetes mellitus or insulin resistance. Interstitial fibrosis of heart occurred in D group and I group. Content of Hydroxyproline, the level of I , III type of collagen, and the total level of collagen in I group were lower than those in D group, and higher than those in N group (P < 0.05). CONCLUSION: Insulin resistance in the rats with type 2 diabetes mellitus or insulin resistance can injury myocardial cell and matrix.