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This study aims to investigate the regulatory effects of Shenling Baizhu Powder(SBP) on cellular autophagy in alcoholic liver disease(ALD) and its intervention effect through the TLR4/NLRP3 pathway. A rat model of chronic ALD was established by gavage of spirits. An ALD cell model was established by stimulating BRL3A cells with alcohol. High-performance liquid chromatography(HPLC) was utilized for the compositional analysis of SBP. Liver tissue from ALD rats underwent hematoxylin-eosin(HE) and oil red O staining for pathological evaluation. Enzyme-linked immunosorbent assay(ELISA) was applied to quantify lipopolysaccharides(LPS), tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β), and interleukin-18(IL-18) levels. Quantitative reverse transcription polymerase chain reaction(qRT-PCR) was conducted to evaluate the mRNA expression of myeloid differentiation factor 88(MyD88) and Toll-like receptor 4(TLR4). The effect of different drugs on BRL3A cell proliferation activity was assessed through CCK-8 analysis. Western blot analysis was performed to examine the protein expression of NOD-like receptor pyrin domain-containing 3(NLRP3), nuclear factor-kappa B P65(NF-κB P65), phosphorylated nuclear factor-kappa B P65(p-P65), caspase-1, P62, Beclin1, and microtubule-associated protein 1 light chain 3(LC3Ⅱ). The results showed that SBP effectively ameliorated hepatic lipid accumulation, reduced liver function, mitigated hepatic tissue inflammation, and reduced levels of LPS, TNF-α, IL-1β, and IL-18. Moreover, SBP exhibited the capacity to modulate hepatic autophagy induced by prolonged alcohol intake through the TLR4/NLRP3 signaling pathway. This modulation resulted in decreased expression of LC3Ⅱ and Beclin1, an elevation in P62 expression, and the promotion of autolysosome formation. These research findings imply that SBP can substantially enhance liver function and mitigate lipid irregularities in the context of chronic ALD. It achieves this by regulating excessive autophagic responses caused by prolonged spirit consumption, primarily through the inhibition of the TLR4/NLRP3 pathway.

Context: Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown., Objective: We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women., Design and Methods: We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments., Results: Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 μM)., Conclusions: This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Oral submucous fibrosis (OSMF) is a kind of chronic, insidious disease, and it is categorized into potentially malignant disorders (PMD), which poses a global and regional problem to public health. It is considered to be a multifactorial disease, such as due to areca nut chewing, trace element disorders, and genetic susceptibility. However, there is still no unanimous conclusion on its pathogenesis, diagnosis, and treatment strategies. Hence, this article provides a comprehensive review and prospect of OSMF research, providing scholars and clinicians with a better perspective and new ideas for the research and treatment of OSMF., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Hui Xu et al.)

Objective: To analyze the clinical characteristics and prognosis of 34 cases of acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITD) and MLL gene rearrangement. Methods: The clinical data of 34 AML patients with FLT3-ITD and MLL gene rearrangement was compared and analyzed for the therapeutic efficacy, prognostic factors when treated with chemotherapy, chemotherapy combined with targeted therapy or allogenic hematopoietic stem cell transplantation (allo-HSCT). Results: Of the thirty-four cases with median age 41 (4-71) years old, 63.6% presented with white blood cells (WBC) greater than 30×10(9)/L, 39.4% greater than 50 × 10(9)/L respectively on admission. M(5) (35.3%) made up the highest proportion. The cytogenetic abnormality reached 61.8%, of which the complex cytogenetic abnormality accounted for 11.8%. Eleven patients (32.35%) had both FLT3-ITD and MLL gene abnormalities. In addition to FLT3 and MLL abnormalities, 23 patients (67.6%) had one or more other gene abnormalities (multiple gene abnormalities). Of the 34 cases, 29.4% patients went into complete remission (CR) after two courses of chemotherapy. 20.6% (7 patients) went into CR after 3 or more courses of chemotherapy. The rate of early relapse in the CR group was 52.9%. Patients with WBC>50×10(9)/L or multiple gene abnormalities had a lower remission rate (7.7%, 5.4%) after two courses of chemotherapy. CR rate for the patients with more than three gene abnormalities was 0. The total 2-year overall survival (OS) in the 34 patients was 28.8% (95% CI 13.5%-46.0%) and the disease-free survival (DFS) was 27.1% (95% CI 12.5%-44.0%). Of the 18 patients treated with chemotherapy alone or chemotherapy combined with targeted therapy, 17 cases died within 2 years and 1 lost follow-up after giving up treatment. For the 16 patients received allo-HSCT, the 3-year OS was 43.4% (95% CI 13.7%-70.4%) and DFS 42.7% (95% CI 13.4%-69.7%). Conclusion: AML patients with FLT3-ITD and MLL gene rearrangement often presented with M(5), accompanied by hyperleukocytosis, cytogenetic or multiple gene abnormalities. Those patients were observed to have low response rate and high early relapse when treated with chemotherapy without allo-HSCT. Patients had multiple gene abnormalities may be an important poor prognostic factor. Allo-HSCT is an effective treatment which could significantly improve the prognosis and survival of AML patients with FLT3-ITD and MLL gene abnormalities.

Objective: To investigate the association of gene polymorphisms of Toll-like receptor 3 (TLR3)-1377C/T and expression of TLR3 with the susceptibility to enterovirus 71 (EV71) encephalitis in children., Methods: A total of 187 children with EV71 infection (59 children in the encephalitis group and 128 in the non-encephalitis group) and 232 children who underwent physical examination were enrolled in the case-control study. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the TLR3-1377C/T gene polymorphisms. ELISA was used to measure the serum level of TLR3., Results: There were no significant differences in the genotype and allele frequencies of TLR3-1377C/T between the non-encephalitis group and the encephalitis group. Compared with the control group, the encephalitis group and the non-encephalitis group had significant increases in the serum level of TLR3 (P<0.05), and the non-encephalitis group had the highest level (P<0.05). The encephalitis group had a significantly higher EV71 viral load than the non-encephalitis group (P<0.01). The children aged <1 year or ≥1 year in the encephalitis group and the non-encephalitis group had significant increases in the serum level of TLR3 compared with their counterparts in the control group (P<0.05), and the children aged <1 year or ≥1 year in the non-encephalitis group had a significantly higher serum level of TLR3 than those in the encephalitis group (P<0.05). In the encephalitis group, the children aged ≥1 year had a significantly higher TLR3 concentration than those aged <1 year (P<0.05), and there were no significant differences in the TLR3 concentration between the children aged ≥1 year and <1 year in the non-encephalitis group and the control group. In the encephalitis group, the proportion of children aged <1 year was significantly higher than those aged ≥1 year (P<0.05)., Conclusions: The TLR3-1377C/T gene polymorphisms are not significantly associated with the development of EV71 encephalitis. Low expression of TLR3 might weaken the inhibitory effect on virus replication and promote the development of EV71 encephalitis. The deficiency in the expression of TLR3 in serum after EV71 infection might be an important factor for the development of encephalitis in infants.

Objective: To investigate the concentrations and clinical significance of secreted frizzled-related protein-1(SFRP1) insaliva and gingival crevicular fluid of patients with oral submucous fibrosis (OSF) as well as the expression of SFRP1 in patients' OSF buccal mucosa. Methods: Twenty OSF patients aged 20 to 40 years old were recruited and randomly divided into two experimental groups, of which were triamcinolone acetonide group and combined triamcinolone acetonide and salvia miltiorrhiza group, respectively. Ten healthy volunteers matchable in sex and age with the patients were recruited as control group. Concentrations of SFRP1 in saliva and gingival crevicular fluid were detected by enzyme-linked immunosorbent assay before and after a continuous treatment of 4 weeks. The visual analogue scale(VAS) pain scores and opening size were also recorded. The expression of SFRP1 in samples from OSF patients' buccal mucosa was also detected using immunohistochemical method. SPSS 16.0 was applied to analyze the results of the experiments. Results: The concentrations of SFRP1 in saliva and gingival crevicular fluid before treatment were (105.8±27.6) ng/L and (84.7±33.2) ng/L in triamcinolone acetonide group, and (86.6±23.2) ng/L and (97.0±23.2) ng/L in combining group, which were both significantly lower( P< 0.01) than that in normal group([153.0±32.8] ng/L and [157.5±31.1] ng/L), respectively. The positive expression rate of SFRP1 in OSF group(10%[2/20]) was significantly lower than that of the control group(10/10)( P< 0.01). After the treatment for 4 weeks, the concentrations of SFRP1 increased to (141.2±35.3) ng/L and (130.6±31.3) ng/L in triamcinolone acetonide group, and to (148.5±65.9) ng/L and (123.0±27.4) ng/L in combining group, which were both significantly higher than those of pre-treatment, respectively( P< 0.01). Conclusions: The concentrations of SFRP1 in saliva and gingival crevicular fluid of OSF patients, which positively corelated to the expression of SFRP1 in OSF patients' buccal mucosa, were significantly lower than that of normal individuals and increased significantly after treatments of local injections of triamcinolone acetonide only or combined with salvia miltiorrhiza.