Entecavir versus tenofovir for prevention of hepatitis B virus-associated hepatocellular carcinoma after curative resection: study protocol for a randomized, open-label trial.

BACKGROUND: Entecavir and tenofovir disoproxil fumarate (TDF) are standard first-line treatments to prevent viral reactivation and hepatocellular carcinoma (HCC) in individuals chronically infected with the hepatitis B virus (HBV), but the long-term efficacy of the two drugs remains controversial. Also unclear is whether the drugs are effective at preventing viral reactivation or HCC recurrence after hepatectomy to treat HBV-associated HCC. This trial will compare recurrence-free survival, overall survival, viral indicators and adverse events in the long term between patients with HBV-associated HCC who receive entecavir or TDF after curative resection. METHODS: This study is a randomized, open-label trial. A total of 240 participants will be randomized 1:1 into groups receiving TDF or entecavir monotherapy. The two groups will be compared in terms of recurrence-free and overall survival at 1, 3, and 5 years after surgery; adverse events; virological response; rate of alanine transaminase normalization; and seroreactivity at 24 and 48 weeks after surgery. DISCUSSION: This study will compare long-term survival between patients with HBV-associated HCC who receive TDF or entecavir monotherapy. Numerous outcomes related to prognosis will be analyzed and compared in this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02650271. Registered on January 7, 2016.

Physical Activity among Rural Residents in Eastern, Central, and Western Provinces of China: A Cross-Sectional Survey.

Physical activity (PA) in which physical exercise (PE) is an important component is probably the most important intervention for preventing noncommunicable diseases (NCDs). However, few studies on PA and PE of rural residents in China were reported. This study conducted the first population-based cross-sectional survey in three provinces of China in 2021 that examined both PA and PE as well as the associated factors of rural residents. The International Physical Activity Questionnaire Short Form (IPAQ-S) was used, and a total of 3780 rural residents were surveyed. The result showed that 22.2% of the rural residents were physical inactivity and rural residents reporting practice of PE was 54.4%. Binary logistic regression analyses showed that being female, people aged between 15 to 34 years or 60 years old and above, employees of governmental departments/retirees, school students, the unemployed, and people with NCDs were risk factors of PA while ethnic minority groups, smoking, and alcohol consumption were risk factors of PE. Health promotion programme aiming at increasing people's PA in rural China is urgently needed, and it should focus on the population groups of the female, people aged 60 years and above, school students, the unemployed, and people with NCDs.

Condensed Fuzheng extract increases immune function in mice with cyclophosphamide-induced immunosuppression.

Our general purpose was to examine the effect of condensed Fuzheng extract (CFE) on the alleviation of immunosuppression. A mouse model of immunosuppression was established by intraperitoneal injection of CTX. A healthy control group received no CTX and no CFE; different intragastric doses of CFE were administered to three groups of mice for 28 days (4500, 2250, or 1125 mg/kg/day); a negative control received CTX alone, and a positive control received CTX and levamisole hydrochloride. We evaluated the effects of CFE on the immune system organs, cells, and molecules by comparing the different groups. CFE significantly improved immune system organs (spleen and thymus indices and histology), stimulated immune cell activities (number of white blood cells and lymphocytes, phagocytosis of mononuclear phagocytes, proliferation of splenic lymphocytes, antibody formation, and NK cell activity), and increased the levels of immunoglobulins (IgA, IgG, and IgM) and cytokines (IL-2 and IFN-γ). Thus CFE effectively alleviated CTX-mediated immunosuppression and oxidative stress and enhanced the immunological functions of mice.

Gut microbiota metabolic characteristics in coronary artery disease patients with hyperhomocysteine.

Hyperhomocysteine (HHcy) is known as a risk factor for coronary artery disease (CAD). Despite the knowledge that gut microbiota related metabolism pathway shares metabolites with that of Hcy, little has been shown concerning the association between HHcy and gut microbiota. To explore their relationship in the context of CAD, 105 patients and 14 healthy controls were recruited from one single medical center located in Beijing, China. Their serum and fecal samples were collected, with multi-omics analyses performed via LC/MS/MS and 16S rRNA gene V3-V4 region sequencing, respectively. Participants from the prospective cohort were divided into CAD, CAD & HHcy and healthy controls (HC) groups based on the diagnosis and serum Hcy concentration. The results revealed significant different metabolic signatures between CAD and CAD & HHcy groups. CAD patients with HHcy suffered a heavier atherosclerotic burden compared to CAD patients, and the difference was closely associated to betaine-homocysteine S-methyltransferase (BHMT)-related metabolites and trimethylamine N-oxide (TMAO)-related metabolites. Dimethylglycine (DMG) exhibited a strong positive correlation with serum total Hcy (tHcy), and TMAO and trimethylysine (TML) were associated with heavier atherosclerotic burden. Multiple other metabolites were also identified to be related to distinct cardiovascular risk factors. Additionally, Clostridium cluster IV and Butyricimonas were enriched in CAD patients with elevated tHcy. Our study suggested that CAD patients with elevated tHcy were correlated with higher atherosclerotic burden, and the impaired Hcy metabolism and cardiovascular risk were closely associated with BHMT-related metabolites, TMAO-related metabolites and impaired gut microbiota homeostasis.

Mechanism of miRNA-based Aconitum leucostomum Worosch. Monomer inhibition of bone marrow-derived dendritic cell maturation.

Delvestidine (DLTD) is a monomeric compound isolated from Aconitum leucostomum Worosch, a widely used medicine for local treatment of rheumatoid arthritis (RA). Studies have shown that Aconitum leucostomum Worosch. can inhibit maturation of bone marrow-derived dendritic cells (BMDCs). Further, microRNAs (miRNAs) have regulatory effects on DC maturity and function. However, the mechanism underlying DLTD effects on DC maturity and RA remains to be elucidated. This study investigated whether DLTD-mediated inhibition of DC maturation is regulated by miRNAs. LPS-induced mature BMDCs were treated with DLTD for 48 h. CD80 and CD86 expression on BMDCs was detected by flow cytometry, and levels of inflammatory factors IL-6, IL-23, IL-1ß, and TNF-α were detected by ELISA and PCR. Further, gene expression and miRNA expression profiles were investigated by bioinformatics analysis and verified by PCR. DLTD was found to inhibit CD80 and CD86 expression on the surface of BMDCs and secretion of inflammatory factors IL-6, IL-23, IL-1ß, and TNF-α. In total, 54 differentially expressed miRNAs were detected, including 29 up-regulated and 25 down-regulated miRNAs after DLTD treatment. Analysis of biological information revealed that the differentially expressed target genes mainly regulated biological processes, including cell differentiation, cell cycle, and protein kinase complexes. Additionally, miR-511-3p downstream targets Calcr, Fzd10, and Eps8, were closely related to BMDCs maturation. DLTD may induce BMDCs maturity through regulation of miRNAs that affect Calcr, Fzd10, and Eps8 gene signals.

LX2343 alleviates cognitive impairments in AD model rats by inhibiting oxidative stress-induced neuronal apoptosis and tauopathy.

Alzheimer's disease (AD) is a progressive neurodegenerative disease leading to the irreversible loss of brain neurons and cognitive abilities, and the vicious interplay between oxidative stress (OS) and tauopathy is believed to be one of the major players in AD development. Here, we demonstrated the capability of the small molecule N-(1,3-benzodioxol-5-yl)-2-[5-chloro-2-methoxy(phenylsulfonyl)anilino]acetamide (LX2343) to ameliorate the cognitive dysfunction of AD model rats by inhibiting OS-induced neuronal apoptosis and tauopathy. Streptozotocin (STZ) was used to induce OS in neuronal cells in vitro and in AD model rats that were made by intracerebroventricular injection of STZ (3 mg/kg, bilaterally), and Morris water maze test was used to evaluate the cognitive dysfunction in ICV-STZ rats. Treatment with LX2343 (5-20 µmol/L) significantly attenuated STZ-induced apoptosis in SH-SY5Y cells and mouse primary cortical neurons by alleviating OS and inhibiting the JNK/p38 and pro-apoptotic pathways. LX2343 was able to restore the integrity of mitochondrial function and morphology, increase ATP biosynthesis, and reduce ROS accumulation in the neuronal cells. In addition, LX2343 was found to be a non-ATP competitive GSK-3ß inhibitor with IC50 of 1.84±0.07 µmol/L, and it potently inhibited tau hyperphosphorylation in the neuronal cells. In ICV-STZ rats, administration of LX2343 (7, 21 mg·kg-1·d-1, ip, for 5 weeks) efficiently improved their cognitive deficits. LX2343 ameliorates the cognitive dysfunction in the AD model rats by suppressing OS-induced neuronal apoptosis and tauopathy, thus highlighting the potential of LX2343 for the treatment of AD.

Berberine protects against lipopolysaccharide-induced intestinal injury in mice via alpha 2 adrenoceptor-independent mechanisms.

AIM: To investigate the mechanisms responsible for the protective action of berberine (Ber) against gut damage in endotoxemic mice. METHODS: Male BALB/c mice were administered intragastrically with distilled water (0.1 mL/10 g), Ber (50 mg/kg) alone, yohimbine (2 mg/kg) alone, or Ber (50 mg/kg) in combination with yohimbine (2 mg/kg) for 3 d. On the third day, lipopolysaccharide (LPS, 18 mg/kg) or normal saline was intraperitoneally injected one hour after the intragastric administration. Following the treatment, intestinal injury in the ileum was histopathologically accessed; enterocyte apoptosis was examined using TUNEL method; Toll-like receptor 4 (TLR4) mRNA expression was measured using RT-PCR assay; inhibitor protein-κBα (I-κBα) phosphorylation and myeloperoxidase content were examined using Western blloting. The macrophage inflammatory protein-2 (MIP-2) production was measured using ELISA assay. RESULTS: Mice challenged with LPS caused extensive ileum injury, including a significantly increased injury score, decreased intestinal villus height, reduced gut mucosal weight and increased intestinal permeability. Furthermore, LPS significantly induced enterocyte apoptosis, increased TLR4 mRNA expression, I-κBα phosphorylation, MIP-2 production and myeloperoxidase content in the ileum. Pretreatment with Ber significantly alleviated all the alterations in the ileum in the endotoxemic mice. Pretreatment with the α2-adrenoceptor antagonist yohimbine did not block the protective action of Ber against LPS-induced intestinal injury. In addition, treatment with yohimbine alone did not prevent LPS-induced intestinal injury. CONCLUSION: Pretreatment with Ber provides significant protection against LPS-induced intestinal injury in mice, via reducing enterocyte apoptosis, inhibiting the TLR4-nuclear factor κB-MIP-2 pathway and decreasing neutrophil infiltration that are independent of α2-adrenoceptors.

Pretreatment with berberine and yohimbine protects against LPS-induced myocardial dysfunction via inhibition of cardiac I-[kappa]B[alpha] phosphorylation and apoptosis in mice.

Myocardial dysfunction is a common complication in sepsis and significantly contributes to the mortality of patients with septic shock. Our previous study demonstrated that pretreatment with berberine (Ber) protected against the lethality induced by LPS, which was enhanced by yohimbine, an [alpha]2-adrenergic receptor antagonist, and Ber combined with yohimbine also improved survival in mice subjected to cecal ligation and puncture. However, no studies have examined whether Ber and yohimbine reduce LPS-induced myocardial dysfunction. Here, we report that pretreatment with Ber, Ber combined with yohimbine, or yohimbine significantly reduced LPS-induced cardiac dysfunction in mice. LPS-provoked cardiac apoptosis, I-[kappa]B[alpha] phosphorylation, IL-1[beta], TNF-[alpha], and NO production were attenuated by pretreatment with Ber and/or yohimbine, whereas cardiac Toll-like receptor 4 mRNA expression, malondialdehyde content, and superoxide dismutase activity were not affected. These data demonstrate for the first time that pretreatment with Ber and/or yohimbine prevents LPS-induced myocardial dysfunction in mice through inhibiting myocardial apoptosis, cardiac I-[kappa]B[alpha] phosphorylation, and TNF-[alpha], IL-1[beta], and NO production, suggesting that activation of [alpha]2-adrenergic receptor in vivo may be responsible at least in part for LPS-induced cardiac dysfunction, and Ber in combination with yohimbine may be a potential agent for preventing cardiac dysfunction during sepsis.

The interfacial dilational properties of hydrophobically modified associating polyacrylamide studied by the interfacial tension relaxation method at an oil-water interface.

The interfacial dilational viscoelastic properties of hydrophobically associating block copolymer composed of acrylamide (AM) and a low amount of 2-phenoxylethyl acrylate (POEA) (<1.0 mol%) at the octane-water interfaces were studied by means of the interfacial tension relaxation method. The dependencies of interfacial dilational elasticity and viscous component on the dilational frequency were investigated. The interaction of hydrophobically associating block copolymer [P(AM/POEA)] with sodium dodecyl sulfate (SDS) has been explored. The results show that at lower frequency, the dilational elasticity for different concentration copolymer is close to zero; at higher frequency, the dilational elasticity shows no change with increased frequency; At moderate frequency (10(-3)-1 Hz), the dilational elasticity decreased with a decrease in the dilational frequency. The results show that the hydrophobic groups of [P(AM/POEA)] chains can be associated by inter- or intrachain liaisons in water solution. The dilational viscous component for P(AM/POEA) comes forth a different maximum value at different frequencies when the polymer concentration is different. It is generally believed that the dilational viscous component reflects the summation of the various microscopic relaxation processes at and near the interface and different relaxation processes have different characteristic frequencies. The spectrum of dilational viscous component may appear more than once maximum values at different frequencies. The influence of SDS on the limiting dilational elasticity and viscous component for polymer solution was elucidated. For 5000 ppm polymer solution, the limiting dilational elasticity decreased with an increase in SDS concentration. The dilational viscous component passed through a maximum value with a rise in the dilational frequency, which appeared at different frequency when SDS concentration is different; and the higher is the concentration, the lower is the dilational frequency. It can be explained that macromolecules may be substituted by SDS molecules in the interface and the interaction of molecules decrease, which makes the limiting dilational elasticity decrease. For 200 ppm polymer solution, the limiting dilational elasticity increased firstly and then decreased with SDS concentration increasing. This may be explained that the interfacial polymer concentration is so low that SDS molecules absorbed in the interface dominate dilational properties of the interfacial film even at very low SDS concentration. However, SDS molecules can gradually substitute the polymer molecules in the interface with a rise in SDS concentration, which results in the decrease in the limiting dilational elasticity.