Trajectories network analysis of chronic diseases among middle-aged and older adults: evidence from the China Health and Retirement Longitudinal Study (CHARLS).

BACKGROUND: Given the increased risk of chronic diseases and comorbidity among middle-aged and older adults in China, it is pivotal to identify the disease trajectory of developing chronic multimorbidity and address the temporal correlation among chronic diseases. METHOD: The data of 15895 participants from the China Health and Retirement Longitudinal Study (CHARLS 2011 - 2018) were analyzed in the current study. Binomial tests and the conditional logistic regression model were conducted to estimate the associations among 14 chronic diseases, and the disease trajectory network analysis was adopted to visualize the relationships. RESULTS: The analysis showed that hypertension is the most prevalent disease among the 14 chronic conditions, with the highest cumulative incidence among all chronic diseases. In the disease trajectory network, arthritis was found to be the starting point, and digestive diseases, hypertension, heart diseases, and dyslipidemia were at the center, while memory-related disease (MRD), stroke, and diabetes were at the periphery of the network. CONCLUSIONS: With the chronic disease trajectory network analysis, we found that arthritis was prone to the occurrence and development of various other diseases. In addition, patients of heart diseases/hypertension/digestive disease/dyslipidemia were under higher risk of developing other chronic conditions. For patients with multimorbidity, early prevention can preclude them from developing into poorer conditions, such as stroke, MRD, and diabetes. By identifying the trajectory network of chronic disease, the results provided critical insights for developing early prevention and individualized support services to reduce disease burden and improve patients' quality of life.

Hepatitis B virus genotype is an independent prognostic factor of telbivudine and tenofovir treatment in hepatitis B surface antigen-positive pregnant women.

To investigate whether HBV genotype influences the effect of tenofovir and telbivudine on HBV DNA and RNA levels in HBsAg-positive pregnant women. This was a retrospective study of 74 HBsAg-positive pregnant women in Guizhou of China. All patients were treated with telbivudine or tenofovir from 12 weeks of pregnancy and HBV infection to the date of delivery. Blood samples were collected at 12-24, 28-32, and 36-40 weeks of pregnancy for the measurement of genotype, HBsAg, hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA, and liver function, including alanine transaminase, aspartate transaminase, total bilirubin, total bile acids, cholinesterase, alkaline phosphatase (ALP), and gamma-glutamyl transferase. All women with HBsAg were followed up. The HBV genotype was B in 64.9% and C in 35.1%. There were 37 patients of telbivudine and tenofovir group respectively. The telbivudine and tenofovir groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log10(HBV DNA), and log10(HBV RNA). Compared with baseline (12-24 weeks), telbivudine group showed a significant increase in ALP and significant reductions in HBsAg, HBeAg, log10(HBV DNA), and log10(HBV RNA) at 36-40 weeks (p < .05). Tenofovir group exhibited a significant increase in ALP and significant reductions in HBeAg, log10(HBV DNA), and log10(HBV RNA) at 36-40 weeks, compared with baseline (p < .05). HBV genotype (B vs. C) was independently associated with HBV DNA change after therapy (p = .005). In telbivudine group, log10 (HBV DNA) increased from 3.38 (2.00-7.30) to 7.43 (4.68-8.70). In tenofovir group, log10 (HBV DNA) decreased from 7.52 (3.32-8.70) to 2.98 (2.00-5.01). HBV genotype was independently associated with HBV DNA change response to telbivudine or tenofovir in pregnant women with hepatitis B. These findings might be helpful for risk assessment regarding vertical transmission of HBV in HBeAg-positive mothers treated with nucleos(t)ide analogues.

The mediating and interacting role of physical activity and sedentary behavior between diabetes and depression in people with obesity in United States.

AIMS: Sufficient physical activity (PA) and less sedentary behavior (SB) have antidepressant effects, however the amount of PA varies according to weight status in adults with diabetes. Given that depression is a common complication of diabetes, we aimed to quantify to what extent the effects of diabetes on the risk of depression were explained by SB or insufficient PA in adults with and without obesity. METHODS: Data were collected from the 2007-2016 National Health and Nutrition Examination Survey (NHANES), which included 22,304 participants aged 20 years or older. The mediation and interaction were evaluated by the four-way effect decomposition method. RESULTS: In individuals suffering from obesity, diabetes, SB, and insufficient moderate and vigorous intensity recreational activity were associated with an increased risk of depression. The increased relative risk of diabetes on depression could be decomposed into a reference interaction (96.78%), a mediated interaction (5.07%), and a pure indirect effect (2.48%), with insufficient moderate-intensity recreational activity as a potential mediator. SB attributed a proportion of 89.21% for the controlled direct effect and 3.64% for pure indirect effect. CONCLUSION: Adults with obesity and diabetes are encouraged to increase moderate-intensity recreational activity and reduce SB, which can greatly prevent the occurrence of depression.

The effects of physical activity and sedentary behavior in the associations between cardiovascular diseases and depression: A four-way decomposition.

BACKGROUND: Negative effects of cardiovascular diseases (CVDs) on depression have been reported, but the relative contribution of physical activity (PA) and sedentary behavior (SB) to such effects remains unclear. Our objective was to precisely quantify the effects modified or mediated by PA and SB using the recently developed four-way effect decomposition. METHODS: Our analysis included 22,117 adults (aged≥20 years) participating in the 2007-2016 National Health and Nutrition Examination Survey (NHANES). Depression was assessed by the Patient Health Questionnaire-9. Moderate recreational activity (MRA), moderate work activity (MWA), and walk or bicycle for transportation, were measured by the Global Physical Activity Questionnaire (GPAQ). A four-way decomposition was applied with PA and SB as mediator to decompose the total effects of CVDs on depression into four components: controlled direct effect (CDE), pure indirect effect (PIE), reference interaction (INTref), and mediated interaction effect (INTmed). RESULTS: There were statistically significant associations between CVDs, MRA, and depression, with the adjusted odds ratios (95% confidence intervals) of being 1.73 (1.42~2.30), 1.81 (1.42~2.30), respectively. With MRA as a mediator, there were interaction and mediation effects in the associations between CVDs and depression, and the proportions attributable of INTref, INTmed, and PIE were 94.08% (P<0.001), 3.92% (P = 0.007), and 1.68% (P = 0.006), respectively. Furthermore, the mediation effect was statistically significant in females rather than males. CONCLUSIONS: MRA strongly modified and mediated the effects of CVDs on depression, especially in females. Our results suggested that sufficient MRA (at least 150 min per week) was considered as requirement for preventing depression in CVDs patients in females.

Efficacy and Safety of Direct Oral Anticoagulants in Elderly Patients With Atrial Fibrillation: A Network Meta-Analysis.

Background: Direct oral anticoagulants (DOACs) have been widely used in patients with atrial fibrillation (AF) for antithrombotic prophylaxis, which were shown to have a favorable risk-benefit profile. However, there are no guidelines for the use of DOACs in elderly patients (aged ≥75 years) with AF, which creates uncertainty about the optimal antithrombotic treatment in these patients. Methods: After comprehensively searching Embase, PubMed, and Cochrane databases, five phase III randomized controlled trials involving 28,137 elderly participants were included in this study. The efficacy outcome was stroke or systemic embolism, and the safety outcome was major bleeding. We conducted a network meta-analysis by using a Bayesian random-effect model for the first time to evaluate the efficacy and safety of main DOACs (apixaban, edoxaban, rivaroxaban, and dabigatran) and warfarin in elderly patients with AF. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were used to assess the effect of drugs on efficacy and safety. The rank probabilities were used to reflect the hierarchy of drugs, and a larger rank probability value symbolized a better rank of drugs. Results: In the prophylaxis of stroke or systemic embolism, apixaban was found to be the best among DOACs compared to warfarin (HR, 0.71; 95% CI: 0.33-1.50), though this finding was not statistically significant. Apixaban ranked the best (rank probabilities, 41.2%) in efficacy of drugs, followed by rivaroxaban, edoxaban, dabigatran, and warfarin (rank probabilities, 31.8, 15.9, 10.9, and 0.2%, respectively). In reducing the risk of major bleeding, apixaban was found to be the best among DOACs too, compared to warfarin (HR, 0.64; 95% CI: 0.33-1.30), though this finding was not statistically significant. In safety, apixaban ranked the best (rank probabilities, 71.4%), followed by edoxaban, dabigatran, warfarin, and rivaroxaban (rank probabilities, 21.0, 5.8, 0.9, and 0.8%, respectively). Conclusions: DOACs showed a lower incidence of stroke/systemic embolism and major bleeding compared with warfarin in antithrombotic therapy in elderly patients (aged ≥75 years), with apixaban being the best of those interventions. Therefore, apixaban should be given priority as an anticoagulant in stroke prevention for elderly patients with AF.

Bone morphogenetic protein-7 represses hepatic stellate cell activation and liver fibrosis via regulation of TGF-ß/Smad signaling pathway.

BACKGROUND: Liver fibrosis is a refractory disease whose persistence can eventually induce cirrhosis or even liver cancer. Early liver fibrosis is reversible by intervention. As a member of the transforming growth factor-beta (TGF-ß) superfamily, bone morphogenetic protein 7 (BMP7) has anti-liver fibrosis functions. However, little is known about BMP7 expression changes and its potential regulatory mechanism as well as the relationship between BMP7 and TGF-ß during liver fibrosis. In addition, the mechanism underlying the anti-liver fibrosis function of BMP7 needs to be further explored. AIM: To investigate changes in the dynamic expression of BMP7 during liver fibrosis, interactions between BMP7 and TGF-ß1, and possible mechanisms underlying the anti-liver fibrosis function of BMP7. METHODS: Changes in BMP7 expression during liver fibrosis and the interaction between BMP7 and TGF-ß1 in mice were observed. Exogenous BMP7 was used to treat mouse primary hepatic stellate cells (HSCs) to observe its effect on activation, migration, and proliferation of HSCs and explore the possible mechanism underlying the anti-liver fibrosis function of BMP7. Mice with liver fibrosis received exogenous BMP7 intervention to observe improvement of liver fibrosis by using Masson's trichrome staining and detecting the expression of the HSC activation indicator alpha-smooth muscle actin (α-SMA) and the collagen formation associated protein type I collagen (Col I). Changes in the dynamic expression of BMP7 during liver fibrosis in the human body were further observed. RESULTS: In the process of liver fibrosis induced by carbon tetrachloride (CCl4) in mice, BMP7 protein expression first increased, followed by a decrease; there was a similar trend in the human body. This process was accompanied by a sustained increase in TGF-ß1 protein expression. In vitro experiment results showed that TGF-ß1 inhibited BMP7 expression in a time- and dose-dependent manner. In contrast, high doses of exogenous BMP7 inhibited TGF-ß1-induced activation, migration, and proliferation of HSCs; this inhibitory effect was associated with upregulation of pSmad1/5/8 and downregulation of phosphorylation of Smad3 and p38 by BMP7. In vivo experiment results showed that exogenous BMP7 improved liver fibrosis in mice. CONCLUSION: During liver fibrosis, BMP7 protein expression first increases and then decreases. This changing trend is associated with inhibition of BMP7 expression by sustained upregulation of TGF-ß1 in a time- and dose-dependent manner. Exogenous BMP7 could selectively regulate TGF-ß/Smad pathway-associated factors to inhibit activation, migration, and proliferation of HSCs and exert anti-liver fibrosis functions. Exogenous BMP7 has the potential to be used as an anti-liver fibrosis drug.

Ferulic acid attenuates liver fibrosis and hepatic stellate cell activation via inhibition of TGF-ß/Smad signaling pathway.

PURPOSE: Liver fibrosis is a worldwide health issue. Development of effective new drugs for treatment of this disease is of great importance. This study investigated the therapeutic effects of ferulic acid on liver fibrosis in vitro and in vivo. MATERIALS AND METHODS: Human hepatic stellate cell line (HSC) LX-2 was used for in vitro assays. Transforming growth factor ß1 (TGF-ß1) was used to induce hepatic fibrosis in LX-2 cells. Western blot was used to detect protein levels of collagen I, fibronectin, α-smooth muscle actin (SMA), p-Smad2, p-Smad3, p-p38, and p-JNK. Gene expression was measured by RT-qPCR. Fluorescence staining was used to determine localization of Smad4. CCl4-induced hepatic fibrosis in SD rats was used as an in vivo model. Histological features were detected by hematoxylin and eosin staining. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hexadecenoic acid (HA), and hydroxyproline (Hyp) were measured by ELISA. RESULTS: TGF-ß1 treatment significantly increased levels of collagen I, fibronectin, α-SMA, p-Smad2, p-Smad3, and Smad4 in LX-2 cells. Ferulic acid improved TGF-ß1-induced hepatic fibrosis via regulation of the TGF-ß1/Smad pathway. Consistent with in vitro data, CCl4 caused severe hepatic fibrosis in SD rats, as determined by ALT, AST, HA, and Hyp upregulation. Protein levels of p-Smad2 and p-Smad3 in liver tissues were significantly increased following treatment with CCl4. All CCL4-induced changes were markedly attenuated by ferulic acid treatment. CONCLUSION: Ferulic acid potently improved hepatic fibrosis via inhibition of the TGF-ß1/Smad pathway in vitro and in vivo. These findings provided evidence for potential use of ferulic acid to treat or prevent liver fibrosis.

[Eighty three cases of post transfusion HCV infection: a 10-year follow up].

OBJECTIVE: To find out clinical characteristics and natural history of post transfusion HCV infection. METHODS: 83 subjects who have received the blood from a same blood donor from January 1998 to July 2002 were investigated by the method combining cross-sectional study with retrospective study. HCV-antibody, HCV RNA, liver function, abdomen B-ultrasound and Fibroscan were detected. RESULTS: The HCV-antibody were all positive. The HCV RNA of 56 out of the 83 cases were positive. The chronicity rates of hepatis C were 76.3% (29/38) in male patients and 60.00% (27/45) in female patients respectively, without significant difference (X² = 2.99, P = 0.11). The average age of the HCV RNA positive patients was (36.54 ± 14.37) years old. The average age of the HCV RNA negative patients was (27.43 ± 12.51) years old. A significant difference (T = -2.41, P = 0.018) existed between. The HCV genotype was type1b. Among the HCV RNA positive patients,10 cases were with mild asthenia, anorexia and abdominal distention, 9 cases with increased serum ALT, 12 cases.with chronic hepatitis and 1 case was diagnosed with decompensated liver cirrhosis. CONCLUSION: The clinical manifestations of HCV infection are occult and chronic. The chronicity rate is related to gender and the age when infection was caught.