A Modified Frailty Phenotype Used for Identifying Frailty in Health Care Practice: Validation Among Chinese Older Adults.

OBJECTIVES: The study aimed to evaluate a simplified and practical frailty detection tool derived from the Fried frailty phenotype (FFP). This tool was developed to facilitate the identification of frail individuals in constrained settings, addressing the challenges posed by uncertain cutoffs of FFP indicators in prompt frailty assessment. DESIGN: A longitudinal study and a cross-sectional study. SETTINGS AND PARTICIPANTS: A total of 1978 older adults aged 67.4 ± 6.16 years from the China Health and Retirement Longitudinal Study (CHARLS), and 972 older adults aged 72.8 ± 6.75 years from a pilot cross-sectional study conducted in Shanghai communities. METHODS: Frailty was assessed according to the FFP criterion. A Chinese modified frailty phenotype (CMFP) was developed, incorporating specific cutoffs for grip strength and an alternative test for walk speed. The internal consistency reliability, the criterion, and predictive validity of the CMFP were evaluated. RESULTS: The 5-time chair stand test (5t-CST) was significantly associated with the 2.5-m walk test (r = 0.373 in the CHARLS and 0.423 in the pilot study). Each element of the CMFP showed moderate to strong correlations with the total CMFP score and showed Cronbach's alpha of 0.303 and 0.358 in both populations. The Spearman's r and kappa values between the CMFP and the FFP were 0.795 and 0.663 in the CHARLS, and 0.676 and 0.537 in the pilot study. The areas under the curve (AUC) were 0.936 and 0.928 in the 2 studies, respectively. In addition, frailty assessed by the CMFP significantly predicted future incidence of outcomes, including all-cause mortality, activities of daily living (ADL)/instrumental ADL disability, hospitalization, and depression. CONCLUSIONS AND IMPLICATIONS: The study demonstrated the CMFP as a valid tool, particularly highlighting its excellent predictive ability on outcomes. The 5t-CST may act as a viable alternative test for assessing slowness. The CMFP can be systematically integrated into preclinical practice to identify frail individuals, especially within constrained spaces.

Diet and lifestyle behaviours simultaneously act on frailty: it is time to move the threshold of frailty prevention and control forward.

BACKGROUND: To analyse the association among the simultaneous effects of dietary intake, daily life behavioural factors, and frailty outcomes in older Chinese women, we predicted the probability of maintaining physical robustness under a combination of different variables. METHODS: The Fried frailty criterion was used to determine the three groups of "frailty", "pre-frailty", and "robust", and a national epidemiological survey was performed. The three-classification decision tree model was fitted, and the comprehensive performance of the model was evaluated to predict the probability of occurrence of different outcomes. RESULTS: Among the 1,044 participants, 15.9% were frailty and 50.29% were pre-frailty; the overall prevalence first increased and then decreased with age, reaching a peak at 70-74 years of age. Through univariate analysis, filtering, and embedded screening, eight significant variables were identified: staple food, spices, exercise (frequency, intensity, and time), work frequency, self-feeling, and family emotions. In the three-classification decision tree, the values of each evaluation index of Model 3 were relatively average; the accuracy, recall, specificity, precision, and F1 score range were between 75% and 84%, and the AUC was also greater than 0.800, indicating excellent performance and the best interpretability of the results. Model 3 takes exercise time as the root node and contains 6 variables and 10 types, suggesting the impact of the comprehensive effect of these variables on robust and non-robust populations (the predicted probability range is 6.67-93.33%). CONCLUSION: The combined effect of these factors (no exercise or less than 0.5 h of exercise per day, occasional exercise, exercise at low intensity, feeling more tired at work, and eating too many staple foods (> 450 g per day) are more detrimental to maintaining robustness.

Inflection Point Age in the Middle and Older Women - Jiangxi Province, China, 2020-2022.

What is already known about this topic?: Previous studies have predominantly examined the micro-level aspects of women aging inflection points, while macro-level research using big data on the inflection points of aging among middle-aged and elderly women in China is currently limited. What is added by this report?: This study determined the inflection ages for physiological, psychological, social, and total dimensions in middle-aged, young elderly, and elderly women [(48.0-53.2) vs. (66.3-70.0) vs. (78.4-81.2) years old]. What are the implications for public health practice?: This study is important for gaining a deeper understanding of aging, identifying patterns of aging, and implementing targeted interventions to promote the overall health of Chinese women.

High blood galectin-3 level associated with risk of frailty in aging.

Background: Frailty is one of the most problematic expressions of population aging, but its underlying mechanism has not been fully elucidated. Circulating galectin-3 (Gal-3) is involved in the pathogenesis of many age-related diseases. This study aims to explore the influence of circulating Gal-3 on the regulation of frailty and aging and to identify the potential mechanism further. Methods: In this cross-sectional analysis, the Fried frailty phenotype (FP) was assessed among 149 community elderly residents in Shanghai. Peripheral blood mononuclear cells (PBMCs) were isolated by the Ficoll-Paque density gradient method, and differentially expressed genes (DEGs) encoding transcription factors in frailty were detected by Illumina and bioinformatics analyzed with R software. Gene Ontology (GO) enrichment analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to explore the functional roles of these DEGs and the target genes related to frailty phenotypes. The serum Gal-3 concentration was tested by enzyme-linked immunosorbent assay (ELISA). Mouse frailty phenotype was used to construct an in vivo model of frailty, after which the serum levels of circulating Gal-3 and its gene expression levels in mouse tissues were determined. Results: Participants' mean age was 72.04 ± 7.05 years. In total, 21.48% were frail and 36.91% were pre-frail. The mean serum Gal-3 concentration was 46.34 ± 17.99 ng/mL in frail participants, 32.30 ± 8.14 ng/mL in pre-frail participants, and 26.00 ± 5.87 ng/mL in non-frail individuals (p < 0.001). Significant positive correlations between serum Gal-3 level and FP score, SARC-F score, C-reactive protein (CRP), interleukin-6, etc., were observed. In addition, the KEGG pathway and GO enrichment analyses showed that 265 DEGs in PBMCs of frail participants were mainly related to inflammatory response, translation, RNA binding, protein binding, ribosome, and primary immunodeficiency. LGALS3 was identified as the overlapping gene between frailty-related DEGs and aging-related DEGs. The elevated serum Gal-3 concentration in the in vivo model of frailty was consistent with the results in participants. Conclusion: In both community-dwelling older adults and aged mice, serum Gal-3 concentration was positively correlated with frailty. This circulating mediator may be a promising indicator of frailty. Clinical trial registration: Chinese Clinical Trial Registry identifier, ChiCTR2000036399.

ACE2 negatively regulates the Warburg effect and suppresses hepatocellular carcinoma progression via reducing ROS-HIF1α activity.

Aerobic glycolysis has pleiotropic roles in the pathogenesis of hepatocellular carcinoma (HCC). Emerging studies revealed key promoters of aerobic glycolysis, however, little is known about its negative regulators in HCC. In this study, an integrative analysis identifies a repertoire of differentially expressed genes (DNASE1L3, SLC22A1, ACE2, CES3, CCL14, GYS2, ADH4, and CFHR3) that are inversely associated with the glycolytic phenotype in HCC. ACE2, a member of the rennin-angiotensin system, is revealed to be downregulated in HCC and predicts a poor prognosis. ACE2 overexpression significantly inhibits the glycolytic flux as evidenced by reduced glucose uptake, lactate release, extracellular acidification rate, and the expression of glycolytic genes. Opposite results are noticed in loss-of-function studies. Mechanistically, ACE2 metabolizes Ang II to Ang-(1-7), which activates Mas receptor and leads to the phosphorylation of Src homology 2-containing inositol phosphatase 2 (SHP-2). SHP2 activation further blocks reactive oxygen species (ROS)-HIF1α signaling. Addition of Ang-(1-7) or the antioxidant N-acetylcysteine compromises in vivo additive tumor growth and aerobic glycolysis induced by ACE2 knockdown. Moreover, growth advantages afforded by ACE2 knockdown are largely glycolysis-dependent. In clinical settings, a close link between ACE2 expression and HIF1α or the phosphorated level of SHP2 is found. Overexpression of ACE2 significantly retards tumor growth in patient-derived xenograft model. Collectively, our findings suggest that ACE2 is a negative glycolytic regulator, and targeting the ACE2/Ang-(1-7)/Mas receptor/ROS/HIF1α axis may be a promising therapeutic strategy for HCC treatment.

Serological analysis of allergic components of house dust mite provides more insight in epidemiological characteristics and clinical symptom development in North China.

Background: House dust mite (HDM) is the most common airborne source causing complex allergy symptoms. There are geographic differences in the allergen molecule sensitization profiles. Serological testing with allergen components may provide more clues for diagnosis and clinical management. Objective: This study aims to investigate the sensitization profile of eight HDM allergen components in a large number of patients enrolled in the clinic and to analyze the relation of gender, age, and clinical symptoms in North China. Methods: The 548 serum samples of HDM-allergic patients (ImmunoCAP® d1 or d2 IgE ≥0.35) were collected in Beijing City and divided in four different age groups and three allergic symptoms. The specific IgE of HDM allergenic components, Der p 1/Der f 1, Der p 2/Der f 2, Der p 7, Der p 10, Der p 21, and Der p 23, was measured using the micro-arrayed allergen test kit developed by Hangzhou Zheda Dixun Biological Gene Engineering Co., Ltd. The new system was validated by comparing to single-component Der p 1, Der p 2, and Der p 23 tests by ImmunoCAP in 39 sera. The epidemiological study of these IgE profiles and the relation to age and clinical phenotypes were analyzed. Results: A greater proportion of male patients was in the younger age groups, while more female patients were in the adult groups. Both the sIgE levels and the positive rates (approximately 60%) against Der p 1/Der f 1 and Der p 2/Der f 2 were higher than for the Der p 7, Der p 10, and Der p 21 components (below 25%). The Der f 1 and Der p 2 positive rates were higher in 2-12-year-old children. The Der p 2 and Der f 2 IgE levels and positive rates were higher in the allergic rhinitis group. The positive rates of Der p 10 increased significantly with age. Der p 21 is relevant in allergic dermatitis symptom, while Der p 23 contributes to asthma development. Conclusion: HDM groups 1 and 2 were the major sensitizing allergens, with group 2 being the most important component relevant to respiratory symptoms in North China. The Der p 10 sensitization tends to increase with age. Der p 21 and Der p 23 might be associated with the development of allergic skin disease and asthma, respectively. Multiple allergen sensitizations increased the risk of allergic asthma.

Are need for affect and cognition culture dependent? Implications for global public health campaigns: a cross-sectional study.

BACKGROUND: Cultural differences in affective and cognitive intrinsic motivation could pose challenges for global public health campaigns, which use cognitive or affective goals to evoke desired attitudes and proactive health-promoting actions. This study aimed to identify cross-cultural differences in affective and cognitive intrinsic motivation and discuss the potential value of this information for public health promotion. METHODS: A cross-sectional survey using cross-culturally validated need for affect (NFA) and need for cognition (NFC) scales was carried out among 1166 Chinese participants, and the results were compared with published data from 980 American participants. Additionally, we assessed a highly prevalent symbolic geriatric health condition, hearing loss, in 500 Chinese community-dwelling seniors. The Chinese NFA scale was developed following the translation-back translation procedure, and the psychometric evaluation was performed by applying confirmatory factor analysis (CFA), exploratory structural equation modeling (ESEM), correlation analysis and multigroup invariance test. MANOVA and Hedge's g statistic were employed to compare the NFA and NFC levels between individuals from different countries and between Chinese seniors with and without hearing loss. The relation of early hearing intervention intention to NFA and NFC was also explored in the Chinese sample. RESULTS: A basic two-factor model of NFA adequately fit the sample data from Chinese and American cultures. The questionnaire demonstrated reasonable invariance of the factor structure and factor loadings across the groups. Those in the primary Chinese sample had lower NFA and NFC than their American peers. This difference held in the senior sample. Moreover, Chinese seniors with hearing loss had even lower NFA and NFC than those without hearing loss. Their early hearing intervention intention was low but was associated with intrinsic motivation. CONCLUSIONS: The Need for Affect (NFA) construct may be generalized beyond its Western origins. There was a general lack of affective and cognitive intrinsic motivation in Chinese individuals, particularly in seniors with hearing loss, compared with their American peers. These differences point to a potential challenge in framing effective messages for some cultures in the geriatric public health domain. Ideally, recognizing and understanding this challenge will inspire the consideration of novel persuasive strategies for these audiences.

Hypoxia-dependent expression of MAP17 coordinates the Warburg effect to tumor growth in hepatocellular carcinoma.

BACKGROUND: Reprogrammed glucose metabolism, also known as the Warburg effect, which is essential for tumor progression, is regarded as a hallmark of cancer. MAP17, a small 17-kDa non-glycosylated membrane protein, is frequently dysregulated in human cancers. However, its role in hepatocellular carcinoma (HCC) remains largely unknown. METHODS: Immunohistochemistry was used to analyze the expression pattern of MAP17 in HCC. Loss-of-function and gain-of-function studies were performed to investigate the oncogenic roles of MAP17 in vitro and in vivo. RNA sequencing, co-immunoprecipitation, immunofluorescence and western blotting were used to study the molecular mechanism of MAP17 affecting the tumor growth and glycolytic phenotype of HCC. RESULTS: An integrative analysis showed that MAP17, a small 17-kDa non-glycosylated membrane protein, is significantly related to the glycolytic phenotype of hepatocellular carcinoma (HCC). Firstly, we found that MAP17 expression is hypoxia-dependent and predicts a poor prognosis in HCC. Genetic silencing of MAP17 reduced the rate of glucose uptake, lactate release, extracellular acidification rate, and expression of glycolytic genes. Ectopic expression of wild type MAP17 but not its PDZ binding domain mutant MAP17-PDZm increased tumor glycolysis. Further research showed that MAP17 knockdown markedly retarded in vivo tumor growth in HCC. Importantly, attenuation of tumor glycolysis by galactose largely hijacked the growth-promoting role of MAP17 in HCC cells. RNA sequencing analysis revealed that MAP17 knockdown leads to transcriptional changes in the ROS metabolic process, cell surface receptor signaling, cell communication, mitotic cell cycle progression, and regulation of cell differentiation. Mechanistically, MAP17 exerted an increased tumoral phenotype associated with an increase in reactive oxygen species (ROS), which activates downstream effectors AKT and HIF1α to enhance the Warburg effect. In HCC clinical samples, there is a close correlation between MAP17 expression and HIF1α or phosphorated level of AKT. CONCLUSIONS: Our results show that MAP17 is a novel glycolytic regulator, and targeting MAP17/ROS pathway may be an alternative approach for the prevention and treatment of HCC.

Radiomics signature on CECT as a predictive factor for invasiveness of lung adenocarcinoma manifesting as subcentimeter ground glass nodules.

Controversy and challenges remain regarding the cognition of lung adenocarcinomas presented as subcentimeter ground glass nodules (GGNs). Postoperative lymphatic involvement or intrapulmonary metastasis is found in approximately 15% to 20% of these cases. This study aimed to develop and validate a radiomics signature to identify the invasiveness of lung adenocarcinoma appearing as subcentimeter ground glass nodules. We retrospectively enrolled 318 subcentimeter GGNs with histopathology-confirmed adenocarcinomas in situ (AIS), minimally invasive adenocarcinomas (MIA) and invasive adenocarcinomas (IAC). The radiomics features were extracted from manual segmentation based on contrast-enhanced CT (CECT) and non-contrast enhanced CT (NCECT) images after imaging preprocessing. The Lasso algorithm was applied to construct radiomics signatures. The predictive performance of radiomics models was evaluated by receiver operating characteristic (ROC) analysis. A radiographic-radiomics combined nomogram was developed to evaluate its clinical utility. The radiomics signature on CECT (AUC: 0.896 [95% CI 0.815-0.977]) performed better than the radiomics signature on NCECT data (AUC: 0.851[95% CI 0.712-0.989]) in the validation set. An individualized prediction nomogram was developed using radiomics model on CECT and radiographic model including type, shape and vascular change. The C index of the nomogram was 0.915 in the training set and 0.881 in the validation set, demonstrating good discrimination. Decision curve analysis (DCA) revealed that the proposed model was clinically useful. The radiomics signature built on CECT could provide additional benefit to promote the preoperative prediction of invasiveness in patients with subcentimeter lung adenocarcinomas.

Validation and psychometric properties of the self-efficacy for Appropriate Medication Use Scale in elderly Chinese patients.

Background Self-efficacy for appropriate medication use is an important construct when evaluating the optimal use of medications. However, no instrument that assesses this construct in elderly Chinese patients has been shown to have valid psychometric properties. Objective To investigate the psychometric properties of the Chinese version of the self-efficacy for Appropriate Medication Use Scale in elderly patients with type 2 diabetes. Setting Geriatric patients were recruited from the endocrinology department of a tertiary hospital in Shanghai, China. Method Self-efficacy was assessed by the Chinese version of the Self-Efficacy for Appropriate Medication Use Scale in subjects who were at least 65 years old. Exploratory and confirmatory factor analyses were used to develop a psychometrically sound model of the scale. Main outcome measures Internal and test-retest reliability; convergent and discriminant validity of the scale; model fit indices of the factor model. Results The two-factor model of the self-efficacy for Appropriate Medication Use Scale was not suitable for elderly patients with respect to both item factor loadings and model fit indices. Conceptually overlapping scale items emerged when the scale was used in these patients. The final model developed appeared to achieve an ideal model fit and presented acceptable convergent and discriminant validity. Conclusions This study presented a Chinese version of the self-efficacy for Appropriate Medication Use Scale with psychometrically sound properties that will enable pharmacists, nurses and physicians to prospectively evaluate the impact of medication self-efficacy on a variety of health outcomes in elderly patients with type 2 diabetes.

Benzo[a]pyrene might be transported by a TonB-dependent transporter in Novosphingobium pentaromativorans US6-1.

Sphingomonads are well known for their ability to efficiently degrade polycyclic aromatic hydrocarbons (PAHs), but little is known about the mechanism of PAH uptake and transport across the cell membrane. RNA sequencing analysis of a sphingomonad, Novosphingobium pentaromativorans US6-1 showed that 38 TonB-dependent transporter (TBDT) genes were significantly upregulated under 5-ring PAH-benzo[a]pyrene (BaP) stress. In order to reveal whether TBDTs are involved in uptake and transport BaP in US6-1, the key TBDT genes were deleted to generate mutants. The results showed that the growth status of these mutants was not different from that of the wild-type strains, but the PAH degradation ability decreased, especially for the mutant strain Δtbdt-11, which did not encode the tbdt-11 gene. Meanwhile, the cell surface hydrophobicity (CSH) of Δtbdt-11 was found to be significantly lower than that of the wild-type strain under BaP stress. Furthermore, the transcriptional activity of genes encoding PAH degradative enzymes was found to be greatly reduced in Δtbdt-11. Confocal microscopy observations showed that US6-1 could transport BaP across the outer membrane, but this transport capacity was significantly reduced in Δtbdt-11 and wild-type US6-1 treated with PMF uncoupler, further confirming that the tbdt-11 gene was associated with PAH active transport.

Impact of a low-carbohydrate and high-fiber diet on nonalcoholic fatty liver disease.

BACKGROUND AND OBJECTIVES: To study the effects of a low-carbohydrate and high-fiber diet and education on patients with nonalcoholic fatty liver disease. METHODS AND STUDY DESIGN: We randomly divided 44 patients with nonalcoholic fatty liver disease into two groups: low-carbohydrate and high-fiber diet and education (intervention group), and education alone (control group). Liver and kidney function, fasting plasma glucose, insulin resistance index, body composition, and controlled attenuation parameter were detected before and after the intervention. RESULTS: After 2 months, the body fat, body weight, abdominal circumference, and visceral fat area, fasting plasma glucose, insulin resistance index, and levels of serum alanine aminotransferase, aspartate transaminase, uric acid, and insulin of the intervention group were significantly lower than before (p<0.05). In the female intervention group, the insulin resistance index and levels of serum alanine aminotransferase, uric acid, triglyceride, fasting plasma glucose, and C-peptide were lower and the level of serum high-density lipoprotein cholesterol was higher than in the female control group (p<0.05). In the male intervention group, the levels of serum alanine aminotransferase, triglyceride, and fasting plasma glucose were lower and the level of serum high-density lipoprotein cholesterol was higher compared with the male control group (p<0.05). CONCLUSIONS: A low-carbohydrate and high-fiber diet and education can effectively reduce the body weight and body fat of patients with nonalcoholic fatty liver disease and improve metabolic indicators such as liver enzymes, blood glucose, blood lipid, and uric acid. Our female patients showed significantly better improvement in the indicators than our male patients.

A parsimonious approach for screening moderate-to-profound hearing loss in a community-dwelling geriatric population based on a decision tree analysis.

BACKGROUND: Hearing loss is one of the most common modifiable factors associated with cognitive and functional decline in geriatric populations. An accurate, easy-to-apply, and inexpensive hearing screening method is needed to detect hearing loss in community-dwelling elderly people, intervene early and reduce the negative consequences and burden of untreated hearing loss on individuals, families and society. However, available hearing screening tools do not adequately meet the need for large-scale geriatric hearing detection due to several barriers, including time, personnel training and equipment costs. This study aimed to propose an efficient method that could potentially satisfy this need. METHODS: In total, 1793 participants (≥60 years) were recruited to undertake a standard audiometric air conduction pure tone test at 4 frequencies (0.5-4 kHz). Audiometric data from one community were used to train the decision tree model and generate a pure tone screening rule to classify people with or without moderate or more serious hearing impairment. Audiometric data from another community were used to validate the tree model. RESULTS: In the decision tree analysis, 2 kHz and 0.5 kHz were found to be the most important frequencies for hearing severity classification. The tree model suggested a simple two-step screening procedure in which a 42 dB HL tone at 2 kHz is presented first, followed by a 47 dB HL tone at 0.5 kHz, depending on the individual's response to the first tone. This approach achieved an accuracy of 91.20% (91.92%), a sensitivity of 95.35% (93.50%) and a specificity of 86.85% (90.56%) in the training dataset (testing dataset). CONCLUSIONS: A simple two-step screening procedure using the two tones (2 kHz and 0.5 kHz) selected by the decision tree analysis can be applied to screen moderate-to-profound hearing loss in a community-based geriatric population in Shanghai. The decision tree analysis is useful in determining the optimal hearing screening criteria for local elderly populations. Implanting the pair of tones into a well-calibrated sound generator may create a simple, practical and time-efficient screening tool with high accuracy that is readily available at healthcare centers of all levels, thereby facilitating the initiation of extensive nationwide hearing screening in older adults.

Circadian Clock Genes in the Metabolism of Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a common disease, which is characterized by the accumulation of triglycerides in the hepatocytes without excess alcohol intake. Circadian rhythms can participate in lipid, glucose, and cholesterol metabolism and are closely related to metabolism seen in this disease. Circadian clock genes can modulate liver lipid metabolism. Desynchrony of circadian rhythms and the influences imparted by external environmental stimuli can increase morbidity. By contrast, synchronizing circadian rhythms can help to alleviate the metabolic disturbance seen in NAFLD. In this review, we have discussed the current research connections that exist between the circadian clock and the metabolism of NAFLD, and we have specifically focused on the key circadian clock genes, Bmal1, Clock, Rev-Erbs, Rors, Pers, Crys, Nocturnin, and DECs.

Huperzine A attenuates nonalcoholic fatty liver disease by regulating hepatocyte senescence and apoptosis: an in vitro study.

OBJECTIVE: This study was undertaken to detect if free fatty acids (FFA) induce hepatocyte senescence in L-02 cells and if huperzine A has an anti-aging effect in fatty liver cells. METHODS: L-02 cells were treated with a FFA mixture (oleate/palmitate, at 3:0, 2:1, 1:1, 1:2 and 0:3 ratios) at different concentrations. Cell viability and fat accumulation rate were assessed by a Cell Counting Kit 8 and Nile Red staining, respectively. The mixture with the highest cell viability and fat accumulation rate was selected to continue with the following experiment. The L-02 cells were divided into five groups, including the control group, FFA group, FFA + 0.1 µmol/L huperzine A (LH) group, FFA + 1.0 µmol/L huperzine A (MH) group and FFA + 10 µmol/L huperzine A (HH) group, and were cultured for 24 h. The expression of senescence-associated ß-galactosidase (SA-ß-gal) was detected by an SA-ß-gal staining kit. The expression levels of aging genes were measured by qRT-PCR. The expression levels of apoptosis proteins were detected by a Western blot. ELISA kits were used to detect inflammatory factors and oxidative stress products. The expression of nuclear factor (NF-κB) and IκBα were detected by immunofluorescence. RESULTS: The FFA mixture (oleate/palmitate, at a 2:1 ratio) of 0.5 mmol/L had the highest cell viability and fat accumulation rate, which was preferable for establishing an in vitro fatty liver model. The expression of inflammatory factors (TNF-α and IL-6) and oxidants Malonaldehyde (MDA), 4-hydroxynonenal (HNE) and reactive oxygen species (ROS) also increased in the L-02 fatty liver cells. The expression levels of aging markers and aging genes, such as SA-ß-gal, p16, p21, p53 and pRb, increased more in the L-02 fatty liver cells than in the L-02 cells. The total levels of the apoptosis-associated proteins Bcl2, Bax, Bax/Bcl-2, CyCt and cleaved caspase 9 were also upregulated in the L-02 fatty liver cells. All of the above genes and proteins were downregulated in the huperzine A and FFA co-treatment group. In the L-02 fatty liver cells, the expression of IκBα decreased, while the expression of NF-κB increased. After the huperzine A and FFA co-treatment, the expression of IκBα increased, while the expression of NF-κB decreased. CONCLUSION: Fatty liver cells showed an obvious senescence and apoptosis phenomenon. Huperzine A suppressed hepatocyte senescence, and it might exert its anti-aging effect via the NF-κB pathway.

Heliangin inhibited lipopolysaccharide-induced inflammation through signaling NF-κB pathway on LPS-induced RAW 264.7 cells.

The heliangin is a natural agent mainly isolated from Helianthus tuberosus L. (Asteraceae). In order to investigate the anti-inflammatory effect of heliangin, several typical models in vivo and in vitro were performed. The RAW264.7 mouse macrophages cells were employed in vitro and dexamethasone were conducted as positive. The cytotoxicity results of heliangin on RAW 264.7 cells provided the safety in vitro for further study. The mRNA of TNF-α, IL-6, iNOS and COX-2 were degraded under heliangin exposure in LPS-stimulated RAW 264.7 cells. The protein expression of iNOS, COX-2 were decreased via heliangin exposure in a dose-dependent manner. Heliangin inhibited TNF-α, NO, IL-6 and PGE2 expression levels in macrophage cells lysate. The immunocytochemistry assay showed the fluorescence image of heliangin treatment intercepted the p65 translocation process from outside to inside of nuclei triggered by LPS. Moreover, we founded that MAPK and NF-κB signaling pathway play important roles in heliangin's activity on RAW264.7 cells. Secondly, the acute toxic study results of heliangin manifested the safety in vivo. Heliangin exerted anti-inflammation effect in a xylene-induced ear swelling in BALB/C mice and carrageenan-induced paw edema model in SD rats. The cytokines levels (TNF-α, IL-6 and PGE2) were decreased. The paw tissue immunochemistry assay demonstrated the IL-6 protein level changes in carrageenan-induced paw edema model under heliangin administration.

Long-term lifestyle interventions in middle-aged and elderly men with nonalcoholic fatty liver disease: a randomized controlled trial.

Nonalcoholic fatty liver disease (NAFLD), a metabolic disorder related to insulin resistance and metabolic syndrome, has become a public health concern. Currently, the principal therapeutic modalities targeting NAFLD are lifestyle interventions. However, the efficacy of long-term lifestyle interventions in managing NAFLD remains largely unexplored. This study aimed to evaluate the efficacy of long-term lifestyle interventions in middle-aged and elderly men with NAFLD. All 280 eligible patients were randomized to the control or test group. Patients in the test group received counseling on diet and exercise from 2 physicians every 3 months via a phone call. Patients in the control group received only counseling in annual checkups without regular intervention. After the 2-year periodic intervention, body weight, abdominal circumference, ALT, TCH, LDL-C and HDL-C decreased in the test group. Specifically, the fatty liver index (FLI) and NAFLD-fibrosis score (NAFLD-FS) reduced markedly in the test group. However, in the control group, there was only a significant decrease in LDL-C, HDL-C and NAFLD-FS (P < 0.001). The liver steatosis grade of the test group decreased significantly, while it increased in the control group. In NAFLD, long-term lifestyle interventions exert an anti-obesity effect and attenuate liver dysfunction and steatosis.

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. A 13C-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.

Association of polymorphisms in survivin gene with the risk of hepatocellular carcinoma in Chinese han population: a case control study.

BACKGROUND: Survivin, one of the strongest apoptosis inhibitors, plays a critical role in the development and progression of hepatocellular carcinoma (HCC). By comparison, relatively little is known about the effect of survivin gene polymorphisms on HCC susceptibility. Our study aimed to investigate the association of survivin gene polymorphisms with the risk of HCC in Chinese han population. METHODS: A case-control study was conducted in Chinese han population consisting of 178 HCC cases and 196 cancer-free controls. Information on demographic data and related risk factors was collected for all subjects. Polymorphisms of the survivin gene, including three loci of rs8073069, rs9904341 and rs1042489, were selected and genotyped by a polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) technique. Association analysis of genotypes/alleles and haplotypes from these loci with the risk of HCC was conducted under different genetic models. RESULTS: Using univariate analysis of rs8073069, rs9904341 and rs1042489 under different genetic models, no statistically significant difference was found in genotype or allele distribution of HCC cases relative to the controls (P > 0.05). Linkage disequilibrium (LD) analysis showed that these loci were in LD. Multivariate logistic regression indicated that with no G-C-T haplotype as reference, the haplotype of G-C-T from these loci was associated with a lower risk for HCC under the recessive model (OR = 0.46, 95% confidence interval (CI): 0.24~0.90, P = 0.023). Both HBsAg+ and the medical history of viral hepatitis type B were risk factors for HCC. However, no statistically significant haplotype-environment interaction existed. CONCLUSIONS: No association between rs8073069, rs9904341 or rs1042489 in survivin gene and the risk of HCC is found in Chinese han population, but rs8073069G-rs9904341C- rs1042489T is perhaps a protective haplotype for HCC.

[Analysis of time trend of hepatocellular carcinoma mortality in Haimen city of Jiangsu province from 1993 to 2006].

OBJECTIVE: To predict the trend of hepatocellular carcinoma (HCC) mortality and investigate the features of its mortality including age, period, and birth cohort in males living in Haimen city of Jiangsu province, China. METHODS: Grey model (GM) was modeled using standardized mortality rate (SMR) of HCC from 1993 to 2006, and was applied to predicting SMR until 2012. Based on the mortality density (MD) for a four-year period, the goodness-of-fit of models and comparisons between models were evaluated so as to obtain the best one among these models including the effects of intercept, age-period-cohort (APC), age-period (AP), age-cohort (AC), period-cohort(PC), and APC. Both APC full model and the best model were used to estimate effects of age, period, and cohort on HCC mortality. In addition, MD form 2005 to 2012 was predicted by the best model. RESULTS: Predictions based on GM (1,1) showed that SMR was 48.578 pre 100 000 population (relative error=-1.267%) in 2007 year, which declined between 2008 and 2012. The lowest value was 45.578 pre 100 000 people (in the 2012 year). The results of fitted models and comparisons between models showed that AP model was the best one (ΔG(2) = 9.065, AIC = 202.544). The curvatures of the effects of the three factors from APC model suggested that significances existed in changes of curvatures of 36.5 - 40.5 years old-(-0.368) and 64.5 - 68.5 years old-(-0.489) as well as in the change of 1956 - 1959 birth cohort (C(2)(1949.5, 1967.5) = -0.492). The estimation of relative risks for AP model showed that the age effects were upward to 64.5 - 68.5 years old-, then downward; and that the period effects were found to be declined between 1993 and 2004. Predictions based on AP model suggested the decrease of HCC mortality. CONCLUSION: The slightly decreasing trend of HCC mortality for males might be explained by age, period and a minor birth cohort effects in Haimen of China.