Zhijun Bao

Cognitive frailty, a novel target for the prevention of elderly dependency

Frailty is a complex and heterogeneous clinical syndrome. Cognitive frailty has been considered as a subtype of frailty. In this study, we refine the definition of cognitive frailty based on existing reports about frailty and the latest progress in cognition research. We obtain evidence from the literature regarding the role of pre-physical frailty in pathological aging. We propose that cognitive impairment of cognitive frailty results from physical or pre-physical frailty and comprises two subtypes: the reversible and the potentially reversible. Reversible cognitive impairment is indicated by subjective cognitive decline (SCD) and/or positive fluid and imaging biomarkers of amyloid-β accumulation and neurodegeneration. Potentially reversible cognitive impairment is MCI (CDR=0.5). Based on the severity of cognitive impairment, it is possible to determine the primary and secondary preventative measures for cognitive frailty. We further determine whether SCD is a component of pre-clinical AD or the early stage of other neurodegenerative diseases, which is required for guiding personal clinical intervention.

Prevalence and factors associated with nonalcoholic fatty liver disease in shanghai work-units

BackgroundsNonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in Asians. However, data on prevalence and factors associated with NAFLD in Asians are lacking. The aim of this study is to investigate the prevalence of NAFLD in Shanghai employees to assess the relationship between NAFLD and age, gender, metabolic risk factors in this studied population.MethodsWe selected 7152 employees of Shanghai work-units. Each of them underwent detailed medical history-taking, physical examination, laboratory assessments and abdominal ultrasonography. The diagnosis of NAFLD was done according to established criteria. Receiver operating characteristics (ROC) curves were applied to detect areas under the ROC curves for each index. Nominal logistic regression analysis was used to estimate the odds ratio for risk factors of NAFLD.ResultsAbout 38.17% employees had NAFLD, more in men than in women. The prevalence of NAFLD increased with increasing age. In both genders, the prevalence of metabolic factors was higher in the NAFLD group. Body max index, waist circumference, weight-to-height ratio, blood pressure, blood glucose, total cholesterol, triglyceride, low density lipoprotein, high density lipoprotein and uric acid were found to have a diagnostic value for NAFLD. Body max index is a better index for diagnosing NAFLD. Uric acid is a new diagnosing index not inferior to lipid metabolic factors. Metabolic factors can increase the risk of NAFLD up to 1.5 ~ 3.8 times.ConclusionsOlder age, male gender, metabolic factors such as obesity, abdominal obesity, dyslipidemia, hypertension or type 2 diabetes are risk factors for NAFLD. Prevalence of NAFLD in Shanghai employees is high. Prevention is extremely important. Those achieve the critical point should have early intervention.

The Neurovascular Protective Effects of Huperzine A on D-Galactose-Induced Inflammatory Damage in the Rat Hippocampus

Background: Chronic administration of <smlcap>D</smlcap>-galactose (<smlcap>D</smlcap>-gal) results in oxidative stress and chronic inflammatory aging. Age-related changes in the brain result in neurovascular damage and blood-brain barrier (BBB) dysfunction. However, little is known regarding <smlcap>D</smlcap>-gal-induced neurovascular damage, as well as the protective effects of huperzine A. Objective: The purpose of this study was to utilize a<smlcap> D</smlcap>-gal-induced rat model to investigate the activation of neurovascular inflammatory damage and apoptosis in the rat hippocampus and to understand whether huperzine A alleviates <smlcap>D</smlcap>-gal-induced neuronal and vascular inflammatory injury. Methods: Aging rats were treated with <smlcap>D</smlcap>-gal (300 mg/kg s.c. for 8 weeks), were coadministered <smlcap>D</smlcap>-gal and huperzine A (<smlcap>D</smlcap>-gal 300 mg/kg and huperzine A 0.1 mg/kg s.c. for 8 weeks) or served as the saline-treated control group rats (same volume of saline given subcutaneously for 8 weeks). Changes in hippocampal morphology and biomarkers of inflammatory damage were analyzed. Results: Our study revealed that chronic administration of <smlcap>D</smlcap>-gal resulted in the activation of glia and vascular endothelial cells and upregulation of mRNA and protein levels of cell-associated adhesion molecules and inflammatory cytokines via nuclear factor (NF)-κB inhibitor degradation and NF-κB nuclear translocation. The inflammatory injury caused significant BBB dysfunction, decreased density of tight junctions (TJs) and apoptosis in the rat hippocampus. Coadministration of huperzine A not only markedly inhibited the <smlcap>D</smlcap>-gal-induced increase in acetylcholinesterase (AChE) activity, but also alleviated <smlcap>D</smlcap>-gal-induced neurovascular damage by inhibiting <smlcap>D</smlcap>-gal-induced NF-κB activation, improving cerebrovascular function and suppressing the <smlcap>D</smlcap>-gal-induced decrease in the density and protein levels of TJs and cell apoptosis. Conclusions: Our findings provided evidence that <smlcap>D</smlcap>-gal induced a proinflammatory phenotype mediated by NF-κB in the rat hippocampus. Moreover, huperzine A suppressed <smlcap>D</smlcap>-gal-induced neurovascular damage and BBB dysfunction, partly by preventing NF-κB nuclear translocation. The inhibiting effect of huperzine A on AChE activity might play an important role in attenuating <smlcap>D</smlcap>-gal-induced inflammatory damage.

Inhibiting CB1 receptors improves lipogenesis in an in vitro non-alcoholic fatty liver disease model

BackgroundThe endocannabinoids system (ECs) mediated mainly by CB1 and CB2 receptors plays an important role in non-alcoholic fatty liver disease by regulating lipid metabolism. This study is to further investigate the expression of CB1 and CB2 in the fat accumulation liver cells and to identify possible underlying mechanism by detecting the key lipogenesis factors.MethodsSodium oleate and sodium palmitate were added into the HepG2 cell line for forming fat accumulation liver cell. MTT assay was used to test the cell’s cytotoxicity. The accumulation rate of fat in HepG2 cell was analyzed by the fluorescent staining. The mRNA and protein expression levels of CB1, CB2, SREBP-1c, ChREBP, L-PK, ACC1, FAS, LXRs and RXR were detected by RT-PCR and Western blot before and after the use of the antagonist.ResultsThe receptors of CB1 were expressed in HepG2 cells with low levels while in HepG2 fatty liver cells with higher levels (p < 0.05). However, after the application of antagonist, the expressions were significantly decreased (p < 0.05). The expressions of SREBP-1c, ChREBP and LXRs were detectable in HepG2 cells and the expressions were increased in HepG2 fatty liver cells (p < 0.05). After using the antagonists, the expressions of SREBP-1c, ChREBP, LXRs, ACC1 and FAS were significantly decreased (p < 0.05). But L-PK and RXR changed little in two groups (p > 0.05).ConclusionResults of the present study demonstrated that CB1 receptors had important pathophysiological effects on the formation of fatty liver. CB1 receptors could be regulated by SREBP-1c, ChREBP and LXRs. Therefore, targeting CB1 receptors for the treatment of NAFLD might have a potential application value.

The efficacy of moxifloxacin-based triple therapy in treatment of Helicobacter pylori infection: a systematic review and meta-analysis of randomized clinical trials

Recent evidence shows that moxifloxacin could exert an antimicrobial effect against Helicobacter pylori in both in vitro and in vivo models. To systematically evaluate whether moxifloxacin-containing triple therapy could improve eradication rates and reduce side effects in first-line or second-line anti-H. pylori treatment, eligible articles were identified by searches of electronic databases. We included all randomized trials comparing moxifloxacin-based triple therapy with standard triple or quadruple therapy during H. pylori eradication treatment. Statistical analysis was performed with Review Manager 5.0.10. Subanalysis/sensitivity analysis was also performed. We identified seven randomized trials (n=1263). Pooled H. pylori eradication rates were 79.03% (95%CI: 75.73-82.07) and 68.33% (95%CI: 64.44-72.04) for patients with moxifloxacin-based triple therapy or with standard triple or quadruple therapy, respectively (intention-to-treat analysis). The odds ratio (OR) was 1.82 (95%CI: 1.17-2.81), the occurrence of total side effects was 15.23% (95%CI: 12.58-18.20) and 27.17% (95%CI: 23.64-30.92) for groups with or without moxifloxacin, and the summary OR was 0.45 (95%CI: 0.26-0.77). In subgroup analyses, we noted that the second-line eradication rate in the moxifloxacin group was significantly higher than that in the quadruple therapy group (73.33 vs 60.17%, OR: 1.78, 95%CI: 1.16-2.73, P<0.001). However, there was no difference in first-line eradication treatment. Findings from this meta-analysis suggest that moxifloxacin-based triple therapy is more effective and better tolerated than standard triple or quadruple therapy. Therefore, a moxifloxacin-based triple regimen should be used in the second-line treatment of H. pylori infection.

Age-related decline in skeletal muscle mass and function among elderly men and women in Shanghai, China: a cross sectional study.

OBJECTIVE To investigate the relationship of muscle mass and muscle function with age. METHODS AND STUDY DESIGN The study including 415 participants (aged 60-99 years). Upper (UMM) and lower (LMM) limbs muscle mass and whole body fat free mass (FFM) were measured by bioelectrical impedance analysis. The appendicular skeletal muscle mass (ASM) index (ASM/height2) was calculated. Muscle function was assessed by measuring hand grip strength (HGS) and gait speed. RESULTS Using ASM index cutoff values we found that higher prevalence of sarcopenia in women than in men (33.5% vs 23.6%, p=0.025). In the upper limb, HGS (β=-0.809) declined more rapidly with age than did UMM (β=-0.592) in men, but not in women (β=-0.389 and β=-0.486 respectively). In the lower limb, gait speed declined more rapidly than LMM in both men (β=-0.683 vs β=-0.442) and women (β=-1.00 vs β=-0.461). The variance of UMM explained 28-29% of the variance of HGS, and LMM explained 7-8% of the variance of gait speed in women and men respectively. In addition to the common predictors (BMI and age), the specific predictors were smoking, exercise and education for FFM and ASM, and smoking, drinking and exercise for HGS (p<0.05). CONCLUSIONS Loss of muscle function is greater than the decline of muscle mass particularly in the upper limbs in men. However, women are more prone to have low muscle mass than the men. Exercise programs need to be designed gender specifically.

Hyperlipidemic versus normal-lipid acute necrotic pancreatitis: proteomic analysis using an animal model.

Objectives Hyperlipidemia is associated with a variety of pancreatic diseases. However, the underlying pathophysiology and molecular mechanisms between hyperlipidemia and acute pancreatitis remain undefined. Gel electrophoresis and mass spectrometry can be used in proteomic analysis to elucidate these mechanisms. Methods A comparative proteomic analysis was conducted to identify proteins that were altered in pancreases of hyperlipidemic acute necrotic pancreatitis rats compared with those of normal-lipid acute necrotic pancreatitis rats. A comparative proteomic approach using a hyperlipidemic rat model was used. Results Thirty-nine differentially expressed proteins were significantly changed in pancreatic samples from hyperlipidemic acute necrotic pancreatitis rats. Differentially expressed proteins in hyperlipidemic pancreatitis include pancreatic proteolytic enzymes, such as lipase, amylase, carboxypolypeptidase, and &agr;-1-antiproteinase; endoplasmic reticulum stress–related proteins; and calcium influx–related proteins including protein disulfide isomerase, calreticulin, annexin A, glucose-regulated protein 78, heat shock protein 60, and peroxiredoxin. Other proteins associated with DNA replication and damage repair, apoptosis, cell metabolism, circulatory dysfunction, and signal transduction were identified in hyperlipidemic pancreatitis. Conclusions Hyperlipidemia intensifies acute necrotic pancreatitis through various ways. These enzymes may be putative biomarkers of hyperlipidemic acute necrotic pancreatitis.

Serum Levels of ApoA1 and ApoA2 Are Associated with Cognitive Status in Older Men

Background. Advancing age, chronic inflammation, oxidative damage, and disorders of lipid metabolism are positively linked to the late-life cognitive impairment. Serum biomarkers may be associated with the cognitive status in older men. Methods. 440 old male subjects with different cognitive functions were recruited to investigate probable serum markers. Pearson Chi-Squared test, univariate analysis, and multivariate logistic regression analysis were performed to evaluate biomarkers which may be associated with cognitive status. Results. Levels of fundus atherosclerosis (AS) (P < 0.001), age (P < 0.001), serum biomarkers peroxidase (POD) (P = 0.026) and interleukin-6 (IL-6) (P = 0.001), serum levels of high-density lipoprotein cholesterol (HDL-C) (P < 0.001), apolipoprotein A2 (ApoA2) (P = 0.001), and ApoC2 (P = 0.005) showed significant differences. Compared to group 3, ApoA1 in group 1 (OR = 1.30, 95% CI 1.01–1.67) and group 2 (OR = 1.47, 95% CI 1.11–1.94) were higher, while ApoA2 were lower (group 1: OR = 0.43, 95% CI 0.18–1.02; group 2: OR = 0.21, 95% CI 0.08–0.54) after adjusting for control variables. Conclusion. The results demonstrated that age, AS levels, POD, IL-6, HDL-C, ApoA2, and ApoC2 were significantly related to cognitive status. Moreover, ApoA1 and ApoA2 were independently associated with cognitive impairment and late-life dementia.

Two-week triple therapy has a higher Helicobacter pylori eradication rate than 1-week therapy: A single-center randomized study.

Background and Aim: To evaluate a high effective and practical regimen for the eradication of Helicobacter pylori infection. Patients and Methods: The 298 patients with H. pylori infection, diagnosed by biopsies performed during the endoscopy, were randomized into two groups. Group 1: Treated for one week with a combination of omeprazole, amoxicillin, and clarithromycin (OAC), named by OAC-1 group (n = 143); Group 2: OAC-2 group (n = 155) treated for two weeks with OAC. The OAC-1 group was treated with triple therapy of omeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg bid for 1 week. OAC-2 group was treated likewise, but for two weeks. A13 C-urea breath test was used to monitor H. pylori after four to eight weeks following therapy. Results: The eradication of infection was 55% and 68% in the OAC-1 and OAC-2 groups, respectively. Moreover, the eradication rates in the two groups were 63% and 75%, respectively. Compared with the OAC-1 group, the efficacy of treatment in the OAC-2 group is significantly higher (P < 0.05). Conclusion: Two-week OAC regimen yields a higher eradication rate of H. pylori, which might be a practical regimen for the eradication of H. pylori.

The Histone Demethylase KDM4D Promotes Hepatic Fibrogenesis by Modulating Toll-Like Receptor 4 Signaling Pathway

Accumulating evidence has revealed the pivotal role of epigenetic regulation in the pathogenesis of liver disease. However, the epigenetic mechanism that accounts for hepatic stellate cells (HSCs) activation in liver fibrosis remains largely unknown. In this study, primary HSCs were used to screen the differentially expressed histone H3 lysine methyltransferases and demethylases during HSC activation. KDM4D was identified as a remarkable up-regulated histone H3 demethylase during HSC activation. The overexpression profile of KDM4D was further confirmed in three fibrosis animal models and human fibrotic liver tissues. In vitro genetic silencing of Kdm4d impaired the collagen gel contraction and migration capacity of primary HSCs. In established CCl4-induced mice model, Kdm4d knockdown inhibited fibrosis progression, and promoted fibrosis reversal, with enhanced thinning and splitting of fibrotic septa, as well as a dramatic decrease in collagen area. Whole gene transcriptome analysis showed the regulatory role of KDM4D in Toll-Like Receptor (TLR) signaling pathway. Mechanistically, KDM4D catalyzed histone 3 on lysine 9 (H3K9) di-, and tri-demethylation, which promoted TLR4 expression, and subsequently prompted liver fibrogenesis by activating NF-κB signaling pathways. KDM4D facilitates TLR4 transcription through demethylation of H3K9, thus activating TLR4/NF-κB signaling pathways in HSCs, contributing to HSC activation and collagen crosslinking, further, hepatic fibrosis progression.