As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

ObjectiveTo understand the current status of Cronobacter sakazakii (Cronobacter spp.) infection and its molecular epidemiological characteristics among patients with diarrhea, so as to provide evidence for the prevention and control of diarrhea disease caused by infection with Cronobacter spp. in Changping District, Beijing. Methods760 stool samples were collected from the diarrhea patients in a sentinel hospital in 2019, for the detection of Cronobacter spp., Salmonella, diarrheogenic Escherichia coli (DEC), and Vibrio Parahaemolyticus. Meanwhile, drug sensitivity experiment and pulsed-field gel electrophoresis (PFGE) typing analysis were conducted on the Cronobacter spp. strains isolated. ResultsA total of 20 Cronobacter spp. strains (2.63%) were isolated, with a lower detection rate than that of Salmonella and Vibrio Parahaemolyticus (χ²=9.052, P=0.011). However, there were no statistically significant differences between the detection rates in Cronobacter spp. and DEC (χ²=1.076, P=0.300). Seasonal characterization analysis showed that Cronobacter spp. could be detected in spring (1.00%), summer (4.17%), autumn (3.00%) and winter (1.67%), and the differences were statistically significant (χ²=662.700, P<0.001). The PFGE analysis showed that 20 PFGE banding patterns were found in 20 Cronobacter spp. strains, with a similarity coefficient ranging from 56.30% to 90.09% and a diverse PFGE banding pattern. The drug sensitivity experiment results showed that 18 (90.00%) strains were resistant to cefazolin, and2 (10.00%) strains were intermediate. While, as for cefoxitin, 2 (10.00%) strains were resistant to it, and 5 (25.00%) strains were intermediate. All the 20 strains were 100.00% sensitive to the other 11 antibiotics. ConclusionIn the study, Cronobacter spp. is detected in all seasons through the year, with a high resistance rate to cefazolin, no multi-drug resistant bacteria appeared, and diverse PFGE banding patterns.

Objective:To investigate the effect of semaglutide on the metabolomics of obese patients with type 2 diabetes mellitus (T2DM) complicated by metabolic-associated fatty liver disease (MAFLD).Methods:A prospective non-randomized controlled study was conducted. Obese patients with T2DM complicated by MAFLD who attended the Department of Endocrinology of Shijiazhuang People′s Hospital from October 2022 to June 2023 were selected as the semaglutide group, and healthy individuals from the physical examination center were selected as the control group. Clinical data of both groups were collected. The semaglutide group was subcutaneously injected with semaglutide following a basic hypoglycemic regimen (starting dose of 0.25 mg once a week, which was changed to 0.5 mg once a week after 1 week for 12 weeks). Liquid chromatography-tandem mass spectrometry was used for qualitative and quantitative analyses of plasma metabolites, and multivariate analysis methods were used to analyze the metabolomics data.Results:In total, 69 patients in the semaglutide group completed the treatment, with 49 males (71%) and a median age of 46 (36, 54) years, and the healthy control group consisted of 100 individuals, with 38 males (38%) and a median age of 40 (35, 45) years. The body mass index and levels of fasting blood glucose, alanine aminotransferase, and interleukin-6 (IL-6) in the semaglutide group before treatment were significantly higher than those in the control group (all P<0.001). The body mass index [23.65 (22.33, 24.45) vs. 28.72 (27.50, 32.07) kg/m 2], liver stiffness measurement [1.61 (0.91, 2.00) vs. 5.78 (5.51, 6.10) kPa], and homeostasis model assessment of insulin resistance index [5.10 (2.90, 7.95) vs. 9.00 (6.25, 11.80)] in the semaglutide group were significantly lower after treatment than before treatment (all P<0.001), and the blood glucose, blood lipid, liver function indicator, and IL-6 levels all significantly decreased after treatment. Metabolomics analysis revealed that there were 219 differential metabolites (131 up-regulated and 88 down-regulated) between the semaglutide group ( n=27) before treatment and the control group ( n=12), with glycerophospholipids and free fatty acids being significantly up-regulated. The semaglutide group showed 203 differential metabolites (121 up-regulated and 82 down-regulated) after treatment compared with before, with significant down-regulation of long-chain fatty acids and significant up-regulation of metabolites including carnitines, branched-chain amino acids, and taurine. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differential metabolites identified before and after semaglutide treatment were involved in several signaling pathways, such as biosynthesis of unsaturated fatty acids, linoleic acid metabolism, aldosterone synthesis and secretion, and the mTOR signaling pathway, etc. Conclusion:Semaglutide alters the serum metabolite levels in obese patients with T2DM complicated by MAFLD.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective In this study,2,4-dinitrochlorobenzene(DNCB)was used to induce the establishment of an atopic dermatitis(AD)model in BALB/c homozygous mice to simulate the skin inflammatory complications in patients with clinical malignancies.Methods BALB/c mice were divided into different groups:negative control group(NC group),model group(MODEL group),atopic dermatitis group(AD group),and dexamethasone group(DEX group).After the mice in MODEL group and DEX group were inoculated with S-180 tumor cells in the axilla,MODEL group,AD group and DEX group were stimulated with DNCB on the dorsal skin and the ear to establish an animal model of atopic dermatitis in tumor-bearing mice.Changes in body weight were observed and recorded,the dorsal skin condition of mice was assessed after the last administration of the drug,the spleen was taken to calculate the spleen coefficient,the difference in the mass of mouse ear slices was determined to calculate the degree of auricular swelling and the rate of inhibition of swelling,and histopathological tests were performed on the dorsal skin tissues to detect the levels of IgE,TNF-α,IL-4,and IL-17 in the serum using an ELISA assay.Results Compared with the NC group,the skin of mice in the MODEL and AD groups showed erythematous,papular,scaly and mossy changes,accompanied by weight loss,and a significant increase in splenic coefficient and auricular swelling.Pathologic findings showed an incomplete skin structure,a significant increase in skin thickness,a large infiltration of inflammatory cells,and an increase in the number of mast cells.Serum levels of IgE,TNF-α,IL-4 and IL-17 were increased.Compared with the MODEL group,the DEX group showed an improvement in all the assays.Conclusions DNCB excitation can successfully establish an animal model of AD in hormonal mice,which is drug-controllable,which provides a useful scientific tool for conducting scientific research related to malignant tumors and skin inflammation.