[Update points for the 2022 edition of the European Association for the Study of Liver Diseases Clinical Practice Guidelines for the Management of Hepatic Encephalopathy and comparison with China's 2018 edition guidelines].

The European Association for the Study of Liver Diseases issued the "Clinical Practice Guidelines for the Management of Hepatic Encephalopathy" in 2022, which included recommendations for clinical diagnosis, assessment, treatment, management, and prevention. The Society's "Hepatic Encephalopathy Clinical Practice Guidelines in Chronic Liver Disease," which was last published in 2014, and the "Guidelines for the Diagnosis and Treatment of Hepatic Encephalopathy in Cirrhosis," which the Chinese Society of Hepatology, Chinese Medical Association, released in 2018, have certain differences and updates in terms of comparison to terminology, grading and classification, diagnosis, clinical evaluation and treatment, management, and prevention. Herein, the updated points of this guideline and the differences between it and our nation's guidelines are summarized in order to refine and understand the guiding role of the new version of the guideline for the clinical treatment of hepatic encephalopathy and provide aid for standardizing clinical diagnosis and treatment.

Mechanism of liver X receptor α and ATP binding cassette transporter A1 involved in preeclampsia using an optimized deep learning model.

OBJECTIVE: Preeclampsia (PE) is a complex disease-causing multisystem damage. Many genes, environmental factors, and their interactions are involved in the development and progression of PE. The pathogenesis of PE is not fully understood, limiting the prevention and treatment of PE. The aim of this study was to investigate the effect of 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS), an ATP-binding cassette transporter A1 (ABCA1) blocker, on apoM mRNA and protein levels. PATIENTS AND METHODS: The role of liver X receptor α (LXRα) and ABCA1 in the pathogenesis of PE was investigated by optimizing the design of DIDS inhibition based on a deep learning model. RESULTS: The proportion of primipara in the research group, EOPE group, LOPE group, and controls was 59.82%, 65.85%, 56.34%, and 21.43%, respectively. The difference between the research group and the controls was statistically significant (p<0.01). In the clinical data, serum-free triiodothyronine (FT3), gestational age at delivery, high-density lipoprotein cholesterol (HDL-C), hemoglobin (HGB), albumin, and platelet (PLT) in the research group were lower than those in the controls (p<0.05). CONCLUSIONS: ABCA1 is considered to affect apoM mRNA expression, G/HDL-C may increase the risk of LOPE, and overweight or obesity, abnormal glycemic regulation, and hypothyroidism are independent risk factors closely related to the pathogenesis of PE and its subgroups.

[Seroprevalence of the specific antibody against Toxoplasma gondii among patients with hematological diseases].

OBJECTIVE: To investigate the seroprevalence of Toxoplasma gondii infections among patients with hematological diseases, so as to provide insights into improving the prognosis and quality of life among patients with hematological diseases. METHODS: A total of 240 patients with hematological diseases (including 170 patients with hematological tumors and 70 patients with non-tumor hematological diseases) admitted to The Affiliated Hospital of Putian University during the period from January 1, 2021 through October 10, 2023 and 500 healthy volunteers in the hospital during the same period were enrolled. Subjects' demographics and serum samples were collected, and serum specific IgG and IgM antibodies against T. gondii were detected using the chemiluminescence assay, with any of a positive IgG or IgM antibody defined as a positive T. gondii infection. The seroprevalence of specific IgG and IgM antibodies against T. gondii was compared between patients with hematological diseases and healthy volunteers. RESULTS: The mean age (F = 2.034, P > 0.05) and gender distribution (χ2 = 0.462, P > 0.05) were comparable among patients with hematological tumors, patients with non-tumor hematological diseases and healthy volunteers, and there was no significant difference in the proportion of history of cat or dog contacts between patients with hematological diseases and healthy volunteers (χ2 = 0, P > 0.05). The seroprevalence of anti-T. gondii antibody was significantly higher among patients with hematological diseases than among healthy volunteers (15.8% vs. 0.6%; χ2 = 71.902, P < 0.01), and there was a significant difference in the seroprevalence of anti-T. gondii antibody among patients with hematological tumors (18.2%), patients with non-tumor hematological diseases (10.0%) and healthy volunteers (χ2 = 78.327, P < 0.01). The seroprevalence of anti-T. gondii antibody was significantly higher among patients with hematological tumors and non-tumor hematological diseases than among healthy volunteers (both P values < 0.05), while no significant difference was seen in the seroprevalence of anti-T. gondii antibody between patients with hematological tumors and non-tumor hematological diseases (P > 0.05). In addition, the proportion of history of cat or dog contacts was significantly higher among patients with hematological diseases that were positive for serum anti-T. gondii anti-body than among those negative for serum anti-T. gondii antibody (21.1% vs. 5.4%; χ2 = 8.653, P < 0.05). CONCLUSIONS: There is a high seroprevalene rate of T. gondii infections among hematological diseases, which is significantly greater than that among healthy volunteers.

CHANGES OF WNT/B-CATENIN SIGNALING AND DIFFERENTIATION POTENTIAL OF BONE MARROW MESENCHYMAL STEM CELLS IN PROCESS OF BONE LOSS IN OVARIECTOMIZED RATS.

BACKGROUND: In vitro studies of the changes about osteoblastogenesis and adipogenesis potential of BMSCs were not clear. As it is the critical pathway for osteogenic differentiation and bone formation, whether or not Wnt/ß-catenin signalling is involved in the changes of osteogenic and adipogenic potential of BMSCs and participates in bone content decrease of ovariectomized (OVX)osteoporosis rats has been rarely reported. MATERIAL/METHODS: BMSCs from femurs of ovariectomzed rats were isolated and cultured in vitro. The proliferation potential of BMSCs was analysed by CCK-8 assays . Osteoblastic and adipogenic differentiation potential of the BMSCs was assessed by ALP activity assay, Alizarin red S staining, Oil red O staining and RT-PCR analysis. RESULTS: The results demonstrated that BMSCs from bilateral ovariectomization rats were endowed with lower proliferation and osteoblastic differentiation potential but higher adipogenic potential than the control group in vitro. In addition, ß-catenin was found to have been decreased in OVX BMSCs, indicating that Wnt/ß-catenin signalling pathways were suppressed in OVX BMSCs . CONCLUSIONS: Results suggested that changes in the Wnt canonical signalling pathway may be related to imbalances of osteogenic and adipogenic potential of BMSCs, and this may be an important factor related to bone content decrease in ovariectomized osteoporosis rats.

Diagnostic potential of urinary monocyte chemoattractant protein-1 for Alzheimer's disease and amnestic mild cognitive impairment.

BACKGROUND AND PURPOSE: The chemokine monocyte chemoattractant protein-1 (MCP-1) is involved in the pathogenesis of Alzheimer's disease (AD). This study aimed to investigate whether urinary MCP-1 can distinguish patients with AD, patients with amnestic mild cognitive impairment (aMCI) and cognitively normal (CN) subjects. METHODS: A total of 754 participants, including 97 patients with AD, 50 patients with aMCI and 84 age- and sex-matched CN controls as well as a cohort of 523 CN subjects of different ages, were enrolled from five hospitals located in different areas of China. Urinary MCP-1 levels were determined using enzyme-linked immunosorbent assays. The correlations between urinary MCP-1 levels and cognition test scores or age were analysed. The optimal diagnostic sensitivity and specificity were determined using receiver operating characteristic curve analysis. RESULTS: In the cohort of CN subjects of different ages, urinary MCP-1 levels increased with ageing and were correlated with age. The urinary MCP-1 levels were higher in females than in males. In the cohort composed of patients with AD, aMCI and age- and sex-matched CN controls, urinary MCP-1 levels were significantly higher in patients with AD and aMCI than in CN controls. There were no differences in urine MCP-1 levels between the AD group and the aMCI group. The urinary MCP-1 levels were correlated with the Mini-Mental State Examination scores and age, and were able to differentiate patients with AD and aMCI from CN subjects. CONCLUSIONS: Urinary MCP-1 is a potential biomarker for the diagnosis of AD and aMCI.

Child, Maternal and Demographic Factors Influencing Caregiver-Reported Autistic Trait Symptomatology in Toddlers.

Current research on children's autistic traits in the general population relies predominantly on caregiver-report, yet the extent to which individual, caregiver or demographic characteristics are associated with informants' ratings has not been sufficiently explored. In this study, caregivers of 396 Singaporean two-year-olds from a birth cohort study completed the Quantitative Checklist for Autism in Toddlers. Children's gender, cognitive functioning and birth order, maternal age, and ethnic group membership were not significant predictors of caregiver-reported autistic traits. Poorer child language development and higher maternal depressive symptoms significantly predicted more social-communicative autistic traits, while lower maternal education predicted more behavioural autistic traits. Children's language and informants' educational level and depressive symptomatology may need to be considered in caregiver-reports of autistic traits.

Wetting behavior of water on silicon carbide polar surfaces.

Technically important wide band-gap semiconductors such as GaN, AlN, ZnO and SiC are crystallized in polar structures. Taking SiC as an example, we investigate the effect of surface polarity on the wetting behavior by water using experiments and molecular dynamic simulations. It is found that the contact angle (CA) of deionized water on the carbon-face (C-face) is significantly larger than that on the silicon-face (Si-face) for both 6H-SiC and 4H-SiC, while the CA of tetrachloromethane is almost the same on these two faces. This finding clearly indicates that polar interactions between water and SiC induce such a large difference in the CA. Extensive molecular dynamics simulations suggest that a larger CA on the C-face than that on the Si-face is resulted from the different charge agglomeration on the two faces. These results will not only be helpful in improving the state of the art processes such as rinsing and wet etching in device fabrication, but also offer a reliable method to determine the polarity of SiC crystals quickly, simply, accurately and nondestructively, which is easily extendable for the measurement of other polar crystals.

The psychometric properties of the Quantitative-Checklist for Autism in Toddlers (Q-CHAT) as a measure of autistic traits in a community sample of Singaporean infants and toddlers.

BACKGROUND: There is growing research evidence that subclinical autistic traits are elevated in relatives of individuals with autism spectrum disorder (ASD), continuously distributed in the general population and likely to share common etiology with ASD. A number of measures have been developed to assess autistic traits quantitatively in unselected samples. So far, the Quantitative-Checklist for Autism in Toddlers (Q-CHAT) is one of very few measures developed for use with toddlers as young as 18 months, but little is known about its measurement properties and factor structure. METHODS: The present study examined internal consistency, factor structure, test-retest stability, and convergent validity of the Q-CHAT in a sample of toddlers in Singapore whose caregivers completed the Q-CHAT at 18 (n = 368) and 24 months (n = 396). RESULTS: Three factors were derived accounting for 38.1 % of the variance: social/communication traits, non-social/behavioral traits, and a speech/language factor. Internal consistency was suboptimal for the total and speech/language scores, but acceptable for the social/communication and non-social/behavioral factor scores. Scores were generally stable between 18 and 24 months. Convergent validity was found with the Pervasive Developmental Disorders subscale of the Child Behavior Checklist (CBCL) completed by caregivers when their children were 24 months. Q-CHAT total scores in this sample were higher than those reported in other unselected samples from the UK. CONCLUSIONS: The Q-CHAT was found to have a three-factor structure, acceptable internal consistency for its two main factor scores (social/communication and non-social/behavioral), normally distributed scores in an unselected sample, and similar structure and measurement properties as those reported in other published studies. Findings are discussed in relation to existing literature and future directions for the validation of the Q-CHAT.

The effect of N-acetyl-glucosamine on stratum corneum desquamation and water content in human skin.

Alpha-hydroxy acids have been used topically to treat skin for both dermatological and cosmetic problems for many years. Though there are many known benefits of the use of alpha-hydroxy acids on skin, there have been recent reports that topical treatments with alpha-hydroxy acids increase skin damage resulting from UVB. Additionally, high concentrations of alpha-hydroxy acids by themselves have also been found to cause skin irritation. In order to find alternatives to alpha-hydroxy acids, we investigated a variety of amino sugar compounds that were previously reported to inhibit the reaggregation of dissociated corneocytes by modulating cellular adhesion. In vivo, we observed that topical treatments with a formulation containing N-acetyl-glucosamine (NAG) led to an increase in skin moisturization, a decrease in skin flakiness, and the normalization of stratum corneum exfoliation. In vitro, we observed an upregulation of differentiation markers, keratin 10 and involucrin, in keratinocytes treated with NAG. CD44 is a lectin cell adhesion molecule that is also expressed in keratinocytes. Amino sugars such as NAG may competitively bind to CD44, modulating keratinocyte cellular adhesion. We hypothesize that these amino sugars modulate keratinocyte cellular adhesion and differentiation, leading to the normalization of stratum corneum exfoliation. We propose the use of amino sugars such as NAG as alternative compounds to replace the use of alpha-hydroxy acids in skin care.

Normal human keratinocytes pretreated with damaged mRNA are resistant to UVB damage and exhibit increased DNA repair.

Treatment of normal human keratinocytes with UVC-irradiated rabbit globin mRNA 24 h before and after UVB exposure increased the survival of the human keratinocytes. We also observed that UVC-damaged mRNA reduced the formation of sunburn cells in skin models. We next tested the effects of UVC-damaged mRNA on cellular repair of DNA. DNA repair was evaluated using 2 assay methods. The first method used a damaged plasmid that is transfected back into the cell where it is repaired by the host cell repair mechanism. In these experiments, we observed that externally added UVC-damaged rabbit globin mRNA enhanced the repair of a plasmid transfected into the host keratinocyte cells. The second method used to determine the effects on DNA repair was direct immunostaining for thymidine-thymidine dimers (TT dimers) in histological sections of the skin models. Skin models were irradiated with UVB and then fixed immediately or after 24 h and stained for TT dimers. UVB irradiation immediately caused an increase in the number of stained keratinocytes in the skin. The number of stained cells decreased in skin fixed 24 h after UVB. This is due to repair of the TT dimers and their removal. Sections of skin models pretreated with UV-damaged mRNA exhibit greater removal of these TT dimers after 24 h. The above evidence suggests that damaged mRNA can trigger a host cell DNA repair pathway.

How does a normal human cell become a cancer cell?

The mechanism by which cells become cancerous has been studied in several different species and cell types. Here, we will focus on the mechanism by which a normal human cell becomes a cancer cell and specifically discuss genes that researchers have used to transform cells. Studying how those genes affect cellular immortalization and transformation will help researchers understand more about cancer biology, find new treatments for cancer and/or improve cell survival during gene therapy.

On the existence and stability of liquid water on the surface of mars today.

The recent discovery of high concentrations of hydrogen just below the surface of Mars' polar regions by Mars Odyssey has enlivened the debate about past or present life on Mars. The prevailing assumption prior to the discovery was that the liquid water essential for its existence is absent. That assumption was based largely on the calculation of heat and mass transfer coefficients or theoretical climate models. This research uses an experimental approach to determine the feasibility of liquid water under martian conditions, setting the stage for a more empirical approach to the question of life on Mars. Experiments were conducted in three parts: Liquid water's existence was confirmed by droplets observed under martian conditions in part 1; the evolution of frost melting on the surface of various rocks under martian conditions was observed in part 2; and the evaporation rate of water in Petri dishes under Mars-like conditions was determined and compared with the theoretical predictions of various investigators in part 3. The results led to the conclusion that liquid water can be stable for extended periods of time on the martian surface under present-day conditions.

Temperature-jump investigations of the kinetics of hydrogel nanoparticle volume phase transitions.

The dynamics of the deswelling and swelling processes in thermoresponsive poly-N-isopropylacrylamide (pNIPAm) hydrogel nanoparticles have been studied by using time-resolved transmittance measurements, in combination with a nanosecond laser-induced temperature-jump (T-jump) technique. A decrease in the solution transmittance associated with deswelling of the particles has been observed as the solution temperature traverses the volume phase transition temperature of the particles. Upon inducing the T-jump, the deswelling transition only occurs in a small percentage (<10%) of the particle volume, which was found to be a thin periphery layer of the particles. The particle deswelling occurs on the microsecond time scale, and as shown previously, the collapse time can be tuned via adding small amounts of hydrophobic component to the particle shell. In contrast, the reswelling of the particles was thermodynamically controlled by bath equilibration, and only small differences in particle reswelling kinetics were found due to sluggish heat dissipation (millisecond time scale) from the sample cell.

Human keratinocytes respond to osmotic stress by p38 map kinase regulated induction of HSP70 and HSP27.

Human skin is exposed to an environment that varies in humidity from 100 to 0%, leading to seasonal variations in the condition of the skin. Exposure to a low humidity environment creates an osmotic gradient across the stratum corneum, which is known to modulate cutaneous barrier function. Heat shock proteins protect against stress-induced destabilization of proteins. We investigated whether osmotic shock (sorbitol) induced a heat shock protein response in normal human keratinocytes, and used heat shock as a positive control. Both heat shock and osmotic stress (200 and 300 mM sorbitol) clearly induced heat shock proteins 70 and 27 mRNA levels. The induction of heat shock protein 70 mRNA levels by osmotic stress peaked at 16 h and persisted until 24 h, whereas upregulation of heat shock protein 70 mRNA levels by heat peaked at 2 h and returned to baseline levels by 6 h. Sorbitol also increased heat shock protein 70 levels in a concentration-dependent manner. The kinetics of heat shock protein 27 mRNA induction by osmotic stress and heat were similar with peak induction at 6 h. The mitogen activated protein kinase family of proteins plays an important part in the coordination of gene responses to various stress conditions. We have demonstrated that the p38 mitogen activated protein kinase was strongly activated by 200 mM and 300 mM sorbitol. The specific p38 mitogen activated protein kinase inhibitor PD169316 almost completely blocked heat shock protein 70 mRNA induction by 200 mM and 300 mM sorbitol and completely suppressed heat shock protein 27 mRNA induction with 200 mM sorbitol. PD169316 also counteracted upregulation of heat shock protein 70 levels by sorbitol. These data indicate that keratinocytes respond to osmotic stress by p38 mitogen activated protein kinase regulated induction of heat shock proteins. This molecular pathway may be relevant for the mechanisms regulating the response of human skin to variations in environmental humidity.

Involvement of Wnt signaling pathway in murine medulloblastoma induced by human neurotropic JC virus.

By using the early genome of the human neurotropic polyomavirus, JCV, we have created transgenic animals that develop cerebellar primitive neuroectodermal tumors which model human medulloblastoma. Expression of T-antigen was found in some, but not all, tumor cells, and examination of the clonal cell lines derived from the tumor population showed enhanced tumorigenicity of cells expressing T-antigen in comparison to T-antigen negative cells. Considering the earlier notion on the potential involvement of beta-catenin with human medulloblastoma, we investigated various components of the Wnt signaling pathway including beta-catenin, its partner transcription factor, LEF-1, and their downstream target gene c-myc in these two cell populations. Immunohistochemical staining of the cells revealed enhanced nuclear appearance of beta-catenin in T-antigen positive cells. Results from Western blot showed higher levels of beta-catenin and LEF-1 in T-antigen positive cells in comparison to those in T-antigen negative cells. The enhanced level of LEF-1 expression correlated with the increase in DNA binding activity of this protein in nuclear extracts of T-antigen positive cells. Results from Northern and Western blot analyses revealed that the level of c-myc expression is augmented both at the RNA and protein levels in T-antigen positive cells. These observations corroborated results from transfection studies indicating the ability of JCV T-antigen to stimulate c-myc promoter activity. Further, co-transfection experiments revealed that the amount of c-myc and T-antigen protein in tumor cells may dictate the activity of JCV early promoter in these cells. These observations are interesting in light of recent discoveries on the association of JCV with human medulloblastoma and suggest that communication between JCV and the Wnt pathway may be an important event in the genesis of these tumors.

Interfacial nonradiative energy transfer in responsive core-shell hydrogel nanoparticles.

Fluorescently labeled core-shell latex particles composed mainly of the thermoresponsive polymer poly-N-isopropylacrylamide (p-NIPAm) have been synthesized such that an energy transfer donor (phenanthrene) and an energy transfer acceptor (anthracene) are covalently localized in the core and shell, respectively. When the thermally induced particle deswelling is interrogated by photon correlation spectroscopy (PCS), a continuous (non-first order) phase transition is observed. Conversely, when the nonradiative energy transfer (NRET) efficiency is used to probe the collapse of these same particles, the phase transition event is observed to occur over a much smaller temperature range and approaches first-order (discontinuous) behavior. Furthermore, core-shell particles with differing shell thicknesses display identical phase transition temperatures when PCS is used to monitor the transition, while NRET measurements show a clear increase in collapse temperature as the shell thickness is increased. These apparently contradictory results are discussed in terms of a radial phase coexistence that exists in the microgel particles, which arises from a similarly radial inhomogeneity in the cross-linker concentration. The prospects for the NRET technique as a molecular-scale probe of nanostructured microgels are also discussed.

Tunable swelling kinetics in core--shell hydrogel nanoparticles.

Thermoresponsive, core--shell poly-N-isopropylacrylamide (p-NIPAm) nanoparticles (microgels) have been synthesized by seed and feed precipitation polymerization, and the influence of chemical differentiation between the core and shell polymers on the phase transition kinetics and thermodynamics has been examined. The results suggest that the core--shell architecture is a powerful one for the design of colloidal "smart gels" with tunable properties. To examine these materials, differential scanning calorimetry (DSC), (1)H NMR, and temperature-programmed photon correlation spectroscopy (TP-PCS) have been employed. These measurements show that the addition of small concentrations of a hydrophobic monomer (butyl methacrylate, BMA) into the particle shell produces large decreases in the rate of thermo-induced particle collapse. Conversely, these low levels of hydrophobic modification do not perturb the thermodynamics of the particle phase transition. When these results are examined in light of previous studies of macroscopic hydrogels, they suggest that the formation of a thin, stable skin layer at the particle exterior during the early stages of particle collapse is the rate limiting factor in particle deswelling. Finally, the hydrophobicity (BMA content) of the shell determines the magnitude of the hydrogel collapse rate, while the thickness of the BMA containing region does not impact the observed kinetics. Together, these results suggest that control over the kinetics of microgel deswelling events can be accomplished simply by modification of the particle periphery, and therefore do not require homogeneous modification of the entire polymer structure.

Successful separation of apoptosis and necrosis pathways in HaCaT keratinocyte cells induced by UVB irradiation.

UVB irradiation can induce apoptotic, necrotic, and differentiation pathways in normal human keratinocytes. The present study was undertaken to determine at what dose of UVB each of these pathways is induced and whether these pathways are distinct or overlapping. We have observed that UVB induces fragmentation of DNA in human HaCaT keratinocytes, in a bimodal manner. Low doses of UVB, 5-20 mJ/cm2, increase the levels of apoptosis as shown by increased levels of fragmented DNA, Fas, PARP, and FasL protein, and the number of apoptotic cells as assessed by FACS analysis. At higher doses of UVB (20 and 30 mJ/cm2) the number of apoptotic cells becomes reduced, as does the amount of Fas, PARP, and FasL protein. At these higher doses, cell viability is decreased as measured by DNA synthesis (BrdU labeling) neutral red uptake, which represents an increasing necrotic phenotype. Expression of markers of keratinocyte differentiation, involucrin, keratin K1, and keratin K10, are also observed to decrease with increasing UVB dose. These changes are accompanied by a further increase in DNA fragmentation. We conclude that low doses of UVB (5-20 mJ/cm2) induced an apoptotic pathway, whereas increasing doses (greater than 20 mJ/cm2) of UVB produce a direct necrotic effect and inhibit terminal differentiation.