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The use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain. A retrospective cohort study. This study was conducted at one tertiary care hospital in China. We evaluated the records of 51,926 Chinese adults who underwent noncardiac surgery from 2013 to 2022. Patients given a combination of hydroxyethyl starch 130/0.4 and crystalloids were propensity-matched at a 1: 1 ratio of baseline characteristics to patients given only crystalloids (11,725 pairs). Eligible patients were divided into those given a combination of hydroxyethyl starch 130/0.4 and crystalloid during surgery and a reference crystalloid group consisting of patients who were not given any colloid. The primary outcome was the incidence of acute kidney injury. Secondarily, acute kidney injury stage, need for renal replacement therapy, intensive care unit transfer rate, and duration of postoperative hospitalization were considered. After matching, hydroxyethyl starch use [8.5 (IQR: 7.5–10.0) mL/kg] did not increase the incidence of acute kidney injury compared with that in the crystalloid group [2.0 vs. 2.2%, OR: 0.90 (0.74–1.08), P = 0.25]. Nor did hydroxyethyl starch use worsen acute kidney injury stage [OR 0.90 (0.75–1.08), P = 0.26]. No significant differences between the fluid groups were observed in renal replacement therapy [OR 0.60 (0.41–0.90), P = 0.02)] or intensive care unit transfers [OR 1.02 (0.95–1.09), P = 0.53] after Bonferroni correction. Even in a subset of patients at high risk of renal injury, hydroxyethyl starch use was not associated with worse outcomes. Hydroxyethyl starch 130/0.4 use was not significantly associated with a greater incidence of postoperative acute kidney injury compared to receiving crystalloid solutions only. •Hydroxyethyl starch 130/0.4 use was not associated with postoperative acute kidney injury.•Postoperative hospitalization slightly longer in hydroxyethyl starch group by median 0.5 days.•No significant difference was found in RRT incidence or ICU transfers.

Background. This study aimed to evaluate the risk factors of HCC development in patients with hepatitis B virus (HBV)-related DC and who underwent long-term antiviral therapy. Methods. Data from 308 patients with HBV-related DC and long-term antiviral therapy were collected and retrospectively reviewed. Cox regression analysis was used to analyze independent risk factors of HCC development. Results. Data from 129 patients with definite records were analyzed. The median follow-up time was 5 years (range, 1 to 8 years). At the end of the follow-up, 41 (31.8%) patients developed HCC, and the time from DC diagnosis to HCC incidence who received antiviral therapy was 4.4 years (range, 1–7 years). The incidence of HCC was higher in males (30/78, 38.5%) than in females (11/51, 21.6%) (P = 0.04). Patients who developed HCC were significantly older than those who did not develop HCC (P < 0.01). The incidence of HCC in patients receiving nucleoside analogues, nucleotide analogues, and combination therapy was 34.7%, 38.1%, and 33.3%, respectively, and the difference showed no significant differences (P = 0.95). Multivariate Cox regression analysis demonstrated that male gender and age ≥50 years are independent risk factors of HCC development (OR = 2.987 and 2.408; 95% CI (1.301–6.858) and (1.126–5.149); P = 0.01 and 0.02, respectively). Conclusion. The risk of HCC remains to be high in patients with HBV-related DC, especially in males aged ≥50 years.

Metabolic dysfunction‐associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease globally. Previous studies have shown that MASLD is an independent risk factor for chronic kidney disease (CKD), but the variations in estimated glomerular filtration rate (eGFR) levels across countries with different ethnic backgrounds have not been extensively reported. We enrolled 3308 participants with biopsy‐proven MASLD from 34 centers in this multinational study and analyzed the associations between eGFR and histological severity of liver fibrosis in different countries. European participants had lower eGFR levels (92.2 ± 20.7 vs. 104.7 ± 17.3 mL/min/1.73 m2) and significant liver fibrosis (61.4 vs. 32.4%) than Asian individuals. In Asia, Chinese participants had the highest mean eGFR level at 105.8 mL/min/1.73 m2, while Malaysian participants had the lowest at 87.3 mL/min/1.73 m2 (p < 0.001). In Europe, French participants had the highest mean eGFR level at 95.3 mL/min/1.73 m2, while Romanian individuals had the lowest at 81.1 mL/min/1.73 m2 (p < 0.001). eGFR levels were inversely associated with liver fibrosis in Asian individuals (OR: 0.793, 95%CI: 0.685–0.917, p = 0.002), even after adjusting for traditional renal risk factors, but not in Europeans. Our findings provide the basis for further investigation of the burden of MASLD on CKD risk in different countries. A total of 3308 participants with biopsy‐proven MASLD from 34 centers were enrolled in the study. We collected liver biopsy pathological scores and clinical parameters and conducted correlation analysis. We finally found that eGFR levels are inversely associated with liver fibrosis in Asians, even after adjusting for traditional renal risk factors.

The objective of this study was to analyze the prevalence of drug-resistant HBV mutants in patients with treatment failure during the past seven years (2010–2016). 4055 HBV-infected patients who underwent HBV polymerase gene mutation test from 2010 to 2016 were enrolled. The nucleos(t)ide analogues (NAs) resistance mutation positions, including rtL180, rtA181, rtT184, rtS202, rtM204, rtI233, rtN236, rtI169, rtV173, and rtM250 were analyzed. Genotypic resistance mutations were detected in 30.8% (1248/4055) of the patients with treatment failure. Rates of drug-resistant mutations associated with LAM, ADV, ETV, and multidrug were 27.23% (1104/4055), 9.67% (392/4055), 3.69% (150/4055), and 0.79% (32/4055). Among the primary NA-resistant mutations, rtM204I (13.44%, 545/4055) occurred more frequently, followed by rtM204V, rtN236T, rtA181T, and rtA181V. For single-base mutations, rtL180M and rtA181V increased gradually during the past seven years, while rtM204I/V and rtN236T decreased after 2015. The development of drug-resistant mutations positively correlated with the consumption of ETV (r = 0.964, P = 0.002), and weakly correlated with that of LAM (r = 0.679, P = 0.109) and ADV (r = 0.429, P = 0.354). Moreover, single-base mutation rtA181V and multi-base mutations (rtL180M + M204I and rtL180M + M204V + M204I) were more common in HBV genotype C than those in genotype B (1.94% vs. 0.66%, 1.84% vs. 0.16%, 1.02% vs. 0.16%, respectively). NA-related mutations in HBV RT region increased in the past seven years, especially for LAM. Frequencies of rtL180M and rtA181T/V increased gradually in the past seven years, to which we should pay more attention.

Considerable studies indicate huperzine A is a promising natural product to suppress neuronal damages induced by β-amyloid (Aβ), a key pathogenic event in the Alzheimer's disease (AD). As an extension, the present study for the first time explored whether the beneficial profiles of huperzine A against oligomeric Aβ(42) induced neurotoxicity are associated with the accumulation and detrimental function of intraneuronal/mitochondrial Aβ, on the basis of the emerging evidence that intracellular Aβ is more relevant to AD progression as compared with extracellular Aβ. Huperzine A treatment was shown to significantly attenuate the neurotoxicity of oligomeric Aβ(42), as demonstrated by increased neuronal viability. Interestingly, our results proved that exogenous Aβ(42) could accumulate intraneuronally in a dose- and time-dependent manner, while huperzine A treatment markedly reduced the level of intracellular Aβ(42). Moreover, huperzine A treatment rescued mitochondrial dysfunction induced by oligomeric Aβ(42), including adenosine triphosphate (ATP) reduction, reactive oxygen species (ROS) overproduction and membrane potential depolarization. Further study demonstrated that huperzine A also significantly reduced the level of Aβ(42) in the mitochondria-enriched subcellular fractions, as well as the Aβ(42) fluorescent signals colocalized with mitochondrial marker. This study indicates that interfering intracellular Aβ especially mitochondrial Aβ accumulation, together with ameliorating Aβ-associated mitochondrial dysfunction, may contribute to the protective effects of huperzine A against Aβ neurotoxicity. Above results may shed more light on the pharmacological mechanisms of huperzine A and provide important clues for discovering novel therapeutic strategies for AD.

Considerable studies indicate huperzine A is a promising natural product to suppress neuronal damages induced by [beta]-amyloid (A[beta]), a key pathogenic event in the Alzheimer's disease (AD). As an extension, the present study for the first time explored whether the beneficial profiles of huperzine A against oligomeric A[beta].sub.42 induced neurotoxicity are associated with the accumulation and detrimental function of intraneuronal/mitochondrial A[beta], on the basis of the emerging evidence that intracellular A[beta] is more relevant to AD progression as compared with extracellular A[beta]. Huperzine A treatment was shown to significantly attenuate the neurotoxicity of oligomeric A[beta].sub.42, as demonstrated by increased neuronal viability. Interestingly, our results proved that exogenous A[beta].sub.42 could accumulate intraneuronally in a dose- and time-dependent manner, while huperzine A treatment markedly reduced the level of intracellular A[beta].sub.42 . Moreover, huperzine A treatment rescued mitochondrial dysfunction induced by oligomeric A[beta].sub.42, including adenosine triphosphate (ATP) reduction, reactive oxygen species (ROS) overproduction and membrane potential depolarization. Further study demonstrated that huperzine A also significantly reduced the level of A[beta].sub.42 in the mitochondria-enriched subcellular fractions, as well as the A[beta].sub.42 fluorescent signals colocalized with mitochondrial marker. This study indicates that interfering intracellular A[beta] especially mitochondrial A[beta] accumulation, together with ameliorating A[beta]-associated mitochondrial dysfunction, may contribute to the protective effects of huperzine A against A[beta] neurotoxicity. Above results may shed more light on the pharmacological mechanisms of huperzine A and provide important clues for discovering novel therapeutic strategies for AD.

In this paper the water absorption properties of polyethylene shrink tape were analyzed for long-distance pipeline. In the water absorption experiments, the normal and high temperature type heat shrinkable tape from six different manufacturers were respectively immersed in water range from 24 h to 28 d. The results show that the water absorption of the normal and high temperature type heat shrinkable tape was steady under the condition of 144 h. Once exceeding 144h, the water absorption increased gradually. Furthermore, the glue layer of heat shrinkable tape had a greater impact on water absorption. And the water absorption of glue layer of heat shrinkable tape decreased with an increase of the hot glue layer thickness,

Considerable studies indicate huperzine A is a promising natural product to suppress neuronal damages induced by beta -amyloid (A beta ), a key pathogenic event in the Alzheimer's disease (AD). As an extension, the present study for the first time explored whether the beneficial profiles of huperzine A against oligomeric A beta 42 induced neurotoxicity are associated with the accumulation and detrimental function of intraneuronal/mitochondrial A beta , on the basis of the emerging evidence that intracellular A beta is more relevant to AD progression as compared with extracellular A beta . Huperzine A treatment was shown to significantly attenuate the neurotoxicity of oligomeric A beta 42, as demonstrated by increased neuronal viability. Interestingly, our results proved that exogenous A beta 42 could accumulate intraneuronally in a dose- and time-dependent manner, while huperzine A treatment markedly reduced the level of intracellular A beta 42. Moreover, huperzine A treatment rescued mitochondrial dysfunction induced by oligomeric A beta 42, including adenosine triphosphate (ATP) reduction, reactive oxygen species (ROS) overproduction and membrane potential depolarization. Further study demonstrated that huperzine A also significantly reduced the level of A beta 42 in the mitochondria-enriched subcellular fractions, as well as the A beta 42 fluorescent signals colocalized with mitochondrial marker. This study indicates that interfering intracellular A beta especially mitochondrial A beta accumulation, together with ameliorating A beta -associated mitochondrial dysfunction, may contribute to the protective effects of huperzine A against A beta neurotoxicity. Above results may shed more light on the pharmacological mechanisms of huperzine A and provide important clues for discovering novel therapeutic strategies for AD.

Aim： To study the conformational changes of Aβ42 and discover novel inhibitors of both Aβ42 aggregation and β-secretase （BACE1）. Methods： A molecular dynamics （MD） simulation at a microsecond level was performed to explore stable conformations of Aβ42 monomer in aqueous solution. Subsequently, structure-based virtual screening was used to search for inhibitors of both Aβ42 aggregation and BACE1. Protein purification and in vitro activity assays were performed to validate the inhibition of the compounds identified via virtual screening. Results： The initial α-helical conformation of Aβ42, which was unstable in aqueous solution, turned into a β-sheet mixed with a coil structure through a transient and fully random coil. The conformation of Aβ42 mainly comprising β-sheets and coils structure was used for further virtual screening. Five compounds were identified as inhibitors for Aβ42 aggregation, and one of them, AE-848, was discovered to be a dual inhibitor of both Aβ42 aggregation and BACE1, with IC50 values of 36.95 μmol/L and 22.70 μmol/L, respectively. Conclusion： A helical to β-sheet conformational change in Aβ42 occurred in a 1.8 microsecond MD simulation. The resulting β-sheet structure of the peptide is an appropriate conformation for the virtual screening of inhibitors against Aβ42 aggregation. Five compounds were identified as inhibitors of Aβ42 aggregation by in vitro activity assays. It was particularly interesting to discover a dual inhibitor that targets both Aβ42 aggregation and BACE1, the two crucial players in the pathogenesis of Alzheimer＇s disease.

During embryogenesis, the liver is the site of hepatogenesis and hematopoiesis and contains many cell lineages derived from the endoderm and mesoderm. However, the characteristics and developmental programs of many of these cell lineages remain unclear, especially in humans. Here, we performed single-cell RNA sequencing of whole human and mouse fetal livers throughout development. We identified four cell lineage families of endoderm-derived, erythroid, non-erythroid hematopoietic, and mesoderm-derived non-hematopoietic cells, and defined the developmental pathways of the major cell lineage families. In both humans and mice, we identified novel markers of hepatic lineages and an ID3 + subpopulation of hepatoblasts as well as verified that hepatoblast differentiation follows the “default-directed” model. Additionally, we found that human but not mouse fetal hepatocytes display heterogeneity associated with expression of metabolism-related genes. We described the developmental process of erythroid progenitor cells during human and mouse hematopoiesis. Moreover, despite the general conservation of cell differentiation programs between species, we observed different cell lineage compositions during hematopoiesis in the human and mouse fetal livers. Taken together, these results reveal the dynamic cell landscape of fetal liver development and illustrate the similarities and differences in liver development between species, providing an extensive resource for inducing various liver cell lineages in vitro.