现行指南建议对ALT升高和HBV DNA 阳性慢性乙型肝炎(CHB)患者给予抗病毒治疗.但越来越多的研究表明,血清高正常ALT(0.5～1 倍正常值上限)慢性HBV感染者的肝组织可见显著坏死炎症和/或纤维化,并存在进展性肝病如肝硬化、肝细胞癌、乙型肝炎相关并发症甚至死亡的风险.本文讨论了血清高正常ALT的定义、血清高正常ALT慢性乙型肝炎患者的临床和病毒学特点,以及对此类患者应否启动抗病毒治疗.
The microstructure evolution and grain growth kinetics of the fine-grained extruded Mg-Nd-Zn-Zr alloy were investigated by holding the extruded plate for a wide range of time in the temperature range ...of 470 °C to 530 °C. By observing the optical micrographs, it was found that the material showed abnormal grain growth at the experimental condition of 470 °C × 24 h, and the time point of abnormal grain growth appeared significantly earlier with the increase in the experimental temperature. The evaluation of the second phase content within the alloy indicates that the presence of the second phase contributes to the microstructural stability of the Mg-Nd-Zn-Zr alloy. However, the slow coarsening/dissolution of the second phase is an important cause of abnormal grain growth. Based on the experimental data, the isothermal grain growth kinetic models of the fine-grained extruded Mg-Nd-Zn-Zr alloy were developed based on the Sellars model. The grain growth exponent was in the range of 5.5-8 and decreased gradually with the increase in the experimental temperature. The grain growth activation energy is approximately 150.00 kJ/mol, which is close to the bulk diffusion activation energy of magnesium, indicating that the grain growth is controlled by lattice diffusion. By energy spectrometry (EDS), the compositional changes of the second phase within this alloy at 500 °C were investigated.
The rate of decline in the levels of neutralizing antibodies (NAbs) greatly varies among patients who recover from Coronavirus disease 2019 (COVID-19). However, little is known about factors ...associated with this phenomenon. The objective of this study is to investigate early factors at admission that can influence long-term NAb levels in patients who recovered from COVID-19. A total of 306 individuals who recovered from COVID-19 at the Tongji Hospital, Wuhan, China, were included in this study. The patients were classified into two groups with high (NAb
,
= 153) and low (NAb
,
= 153) levels of NAb, respectively based on the median NAb levels six months after discharge. The majority (300/306, 98.0%) of the COVID-19 convalescents had detected NAbs. The median NAb concentration was 63.1 (34.7, 108.9) AU/mL. Compared with the NAb
group, a larger proportion of the NAb
group received corticosteroids (38.8% vs. 22.4%,
= 0.002) and IVIG therapy (26.5% vs. 16.3%,
= 0.033), and presented with diabetes comorbidity (25.2% vs. 12.2%,
= 0.004); high blood urea (median (IQR): 4.8 (3.7, 6.1) vs. 3.9 (3.5, 5.4) mmol/L;
= 0.017); CRP (31.6 (4.0, 93.7) vs. 16.3 (2.7, 51.4) mg/L;
= 0.027); PCT (0.08 (0.05, 0.17) vs. 0.05 (0.03, 0.09) ng/mL;
= 0.001); SF (838.5 (378.2, 1533.4) vs. 478.5 (222.0, 1133.4) μg/L;
= 0.035); and fibrinogen (5.1 (3.8, 6.4) vs. 4.5 (3.5, 5.7) g/L;
= 0.014) levels, but low SpO
levels (96.0 (92.0, 98.0) vs. 97.0 (94.0, 98.0)%;
= 0.009). The predictive model based on Gaussian mixture models, displayed an average accuracy of 0.7117 in one of the 8191 formulas, and ROC analysis showed an AUC value of 0.715 (0.657-0.772), and specificity and sensitivity were 72.5% and 67.3%, respectively. In conclusion, we found that several factors at admission can contribute to the high level of NAbs in patients after discharge, and constructed a predictive model for long-term NAb levels, which can provide guidance for clinical treatment and monitoring.
Reservoir operation optimization is a technical measure for flood control and is beneficial owing to its reasonable and reliable control and application of existing water conservancy and hydropower ...hubs, while ensuring dam safety and flood control, as well as the normal operation of power supply and water supply. Considering the beneficial functions of reservoirs, namely flood control and ecological protection, this paper firstly established a two-objective optimal operation model for the reservoir group in the middle reaches of the Yellow River. We aim to maximize the average output of the cascade reservoir group and minimize the average change in ecological flow during the operation period under efficient sediment transport conditions, with the coordination degree of water and sediment as the constraints of reservoir discharge flows. The paper aims to construct an evaluation index system for reservoir operation schemes, apply a combined approach of objective and subjective evaluations, and introduce the gray target and cumulative prospect theories. By uniformly quantifying the established scheme evaluation index system, screening the reservoir operation schemes with the fuzzy evaluation method, and selecting the recommended scheme for each typical year, this paper provides a new scientific formulation of the operation schemes of reservoirs in the middle reaches of the Yellow River. The selected schemes are compared with actual data, demonstrating the effectiveness of joint reservoir operation and for multidimensional benefits in terms of power generation, ecology, and flood control.
has been identified as the causal gene for primary microcephaly type 1, a neurodevelopmental disorder characterized by reduced brain size and delayed growth. As a multifunction protein, MCPH1 has ...been reported to repress the expression of TERT and interact with transcriptional regulator E2F1. However, it remains unclear whether MCPH1 regulates brain development through its transcriptional regulation function. This study showed that the knockout of
in mice leads to delayed growth as early as the embryo stage E11.5. Transcriptome analysis (RNA-seq) revealed that the deletion of
resulted in changes in the expression levels of a limited number of genes. Although the expression of some of E2F1 targets, such as
and
, was affected, the differentially expressed genes (DEGs) were not significantly enriched as E2F1 target genes. Further investigations showed that primary and immortalized
knockout mouse embryonic fibroblasts (MEFs) exhibited cell cycle arrest and cellular senescence phenotype. Interestingly, the upregulation of p19ARF was detected in
knockout MEFs, and silencing
restored the cell cycle and growth arrest to wild-type levels. Our findings suggested it is unlikely that MCPH1 regulates neurodevelopment through E2F1-mediated transcriptional regulation, and p19ARF-dependent cell cycle arrest and cellular senescence may contribute to the developmental abnormalities observed in primary microcephaly.
: Depression is a sickening psychiatric condition that is prevalent worldwide. To manage depression, the underlying modes of antidepressant effect of herbals are important to be explored for the ...development of natural drugs. Tiansi Liquid is a traditional Chinese medicine (TCM) that is prescribed for the management of depression, however its underlying mechanism of action is still uncertain. The purpose of this study was to systematically investigate the pharmacological mode of action of a herbal formula used in TCM for the treatment of depression.
: Based on literature search, an ingredients-targets database was developed for Tiansi Liquid, followed by the identification of targets related to depression. The interaction between these targets was evaluated on the basis of protein-protein interaction network constructed by STITCH and gene ontology (GO) enrichment analysis using ClueGO plugin.
: As a result of literature search, 57 components in Tiansi Liquid formula and 106 potential targets of these ingredients were retrieved. A careful screening of these targets led to the identification of 42 potential targets associated with depression. Ultimately, 327 GO terms were found by analysis of gene functional annotation clusters and abundance value of these targets. Most of these terms were found to be closely related to depression. A significant number of protein targets such as IL10, MAPK1, PTGS2, AKT1, APOE, PPARA, MAPK1, MIF, NOS3 and TNF-α were found to be involved in the functioning of Tiansi Liquid against depression.
: The findings elaborate that Tiansi Liquid can be utilized to manage depression, however, multiple molecular mechanisms of action could be proposed for this effect. The observed core mechanisms could be the sensory perception of pain, regulation of lipid transport and lipopolysaccharide-mediated signaling pathway.
This paper proposes a new water transfer triggering mechanism for multi-reservoir system to divert water from abundant to scarce regions with a constant diversion flow in an inter-basin water ...transfer-supply project. Taking into account of the uncertain nature of inflow, the storage of reservoir is taken as a signal for decision-making to indicate water abundance or water scarcity. In this study, a set of rule curves based on storage of donor reservoir and storage of recipient reservoir are used together to determine when to start water transfer. To initiate water diversion to each recipient reservoir effectively, several water transfer rule curves of the donor reservoir are set for each recipient reservoir respectively in the multi-reservoir system with one donor reservoir and several recipient reservoirs, which is the main difference in comparison with other water transfer triggering mechanisms. In addition, a systematic framework is developed to integrate the water transfer rule curves with hedging rule curves to simultaneously solve the water transfer and water supply problems, since they interact with each other during the operation process. In order to verify the utility of the new water transfer triggering mechanism, an inter-basin water transfer-supply project in China is used as a case study and an improved particle swarm optimization algorithm (IPSO) with a simulation model is adopted for optimizing the decision variables. The results show that the proposed water transfer triggering mechanism can improve the operation performances of the inter-basin system.
Microbial community succession during decomposition has been proven to be a useful tool for postmortem interval (PMI) estimation. Numerous studies have shown that the intestinal microbial community ...presented chronological changes after death and was stable in terrestrial corpses with different causes of death. However, the postmortem pattern of intestinal microbial community succession in cadavers retrieved from water remains unclear. For immersed corpses, the postmortem submersion interval (PMSI) is a useful indicator of PMI. To provide reliable estimates of PMSI in forensic investigations, we investigated the gut microbial community succession of corpses submersed in freshwater and explored its potential application in forensic investigation. In this study, the intestinal microbial community of mouse submersed in freshwater that died of drowning or CO
asphyxia (i.e., postmortem submersion) were characterized by 16S rDNA amplification and high-throughput sequencing, followed by bioinformatic analyses. The results demonstrated that the chronological changes in intestinal bacterial communities were not different between the drowning and postmortem submersion groups. α-diversity decreased significantly within 14 days of decomposition in both groups, and the β-diversity bacterial community structure ordinated chronologically, inferring the functional pathway and phenotype. To estimate PMSI, a regression model was established by random forest (RF) algorithm based on the succession of postmortem microbiota. Furthermore, 15 genera, including
,
, and others, were selected as candidate biomarkers to set up a concise predicted model, which provided a prediction of PMSI MAE (± SE) = 0.818 (± 0.165) d. Overall, our present study provides evidence that intestinal microbial community succession would be a valuable marker to estimate the PMSI of corpses submerged in an aquatic habitat.
Intestinal mycobiome dysbiosis plays an important role in the advancement of HIV- and HCV-infected patients. Co-infection with HCV is an important risk factor for exacerbating immune activation in ...HIV-infected patients, and gut fungal microbial dysbiosis plays an important role. However, no systematic study has been conducted on the intestinal fungal microbiome of HIV/HCV co-infected patients to date. Patients infected with HIV and HCV, either alone or in combination, and healthy volunteers were included. Stool samples were collected for fungal ITS sequencing and for further mycobiome statistical analysis. We found that the abundance of fungal species significantly decreased in the HIV/HCV co-infection group compared to in the healthy control group, while no significant differences were found in the mono-infection groups. Low-CD4 + T-cell patients in the HIV group and high-ALT-level patients in the HCV group were discovered to have a more chaotic fungal community. Furthermore, the opportunistic pathogenic fungal profiles and fungal inter-correlations in the co-infection group became less characteristic but more complicated than those in the mono-infection groups. Intestinal fungal dysregulation occurs in HIV- and HCV-infected patients, and this dysregulation is further complicated in HIV/HCV co-infected patients.
Our study aimed to determine the impact of HIV coinfection on the natural progression of liver disease in treatment-naive HCV-infected patients. From 2009 to 2017, we tracked non-invasive markers of ...liver fibrosis and end-stage liver disease (ESLD)-associated mortality among HCV mono-infected and HIV/HCV coinfected patients in an impoverished village in China. The study cohort consisted of 355 HBsAg-negative and anti-HCV (+) or anti-HIV (+) patients recruited in July 2009, 164 of whom were diagnosed with HIV-1 infection. The surviving patients were re-evaluated in August 2017. During the follow-up, the disease status, liver biochemical, and non-invasive indicators of liver fibrosis (APRI and FIB-4) were measured. The transaminases ALT and AST were significantly higher in HIV-positive HCV resolvers (HIV+ HCVr) than in HIV-negative HCV resolvers (HCVr) (p = 0.019 and p < 0.0001, respectively). APRI and FIB-4 scores of HIV-positive chronic HCV carriers (HIV+ HCVc) were significantly higher than in HIV-negative chronic HCV carriers (HCVc) (p < 0.001). Similarly, APRI and FIB-4 scores were higher in the HIV+ HCVr group than in the HCVr group (ps < 0.001). From 2009 to 2017, the levels of ALT (p = 0.006), AST (p = 0.003), APRI (p = 0.015), and FIB-4 (p = 0.025) were significantly elevated in the HIV/HCV coinfected patients with CD4+ T counts below 500 cells/l. ESLD-related mortality was significantly greater in HIV/HCV-infected cases than in HCV mono-infected patients (73.3% vs. 31.3%, p = 0.009) among patients (n = 45) who died between 2009 and 2017 during follow-up. These findings suggest a higher risk of ESLD-related death and rapid progression of liver fibrosis in HIV/HCV coinfected individuals compared with HCV mono-infected patients. During HIV/HCV coinfection, HIV infection may aggravate HCV-associated liver injury.
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