Chronic hepatitis B (CHB) poses a major global public health challenge and is a leading cause of cirrhosis and liver cancer. Hepatic steatosis is common in individuals with CHB compared to the non-CHB population and is particularly prevalent in hepatitis B virus (HBV)-endemic regions, affecting about one-third of CHB patients. The interaction between hepatic steatosis and CHB-related disease progression is complex and still under debate. Evidence demonstrates that co-existing steatosis may worsen liver fibrosis while paradoxically increasing the likelihood of achieving better HBV control. In particular, despite the association of steatotic liver disease (SLD) with lower HBV viral loads and higher rates of HBsAg seroclearance, the coexistence of CHB and SLD can potentially accelerate liver disease progression. Factors such as fat deposition, lipotoxicity, oxidative stress, and chronic inflammation in SLD may foster a pro-fibrotic and pro-carcinogenic environment, accelerating the disease progression. Additionally, loss of global DNA methylation, changes in the immune microenvironment, and genetic susceptibility further contribute to the development of CHB-related cirrhosis and hepatocellular carcinoma (HCC). This review examines the mechanisms driving liver disease progression and the heightened risk of cirrhosis and HCC in patients with concurrent CHB and steatotic liver disease, underscoring the importance of prioritizing antiviral therapy for CHB in addition to addressing SLD.

Chronic hepatitis B (CHB) poses a major global public health challenge and is a leading cause of cirrhosis and liver cancer. Hepatic steatosis is common in individuals with CHB compared to the non-CHB population and is particularly prevalent in hepatitis B virus (HBV)-endemic regions, affecting about one-third of CHB patients. The interaction between hepatic steatosis and CHB-related disease progression is complex and still under debate. Evidence demonstrates that co-existing steatosis may worsen liver fibrosis while paradoxically increasing the likelihood of achieving better HBV control. In particular, despite the association of steatotic liver disease (SLD) with lower HBV viral loads and higher rates of HBsAg seroclearance, the coexistence of CHB and SLD can potentially accelerate liver disease progression. Factors such as fat deposition, lipotoxicity, oxidative stress, and chronic inflammation in SLD may foster a pro-fibrotic and pro-carcinogenic environment, accelerating the disease progression. Additionally, loss of global DNA methylation, changes in the immune microenvironment, and genetic susceptibility further contribute to the development of CHB-related cirrhosis and hepatocellular carcinoma (HCC). This review examines the mechanisms driving liver disease progression and the heightened risk of cirrhosis and HCC in patients with concurrent CHB and steatotic liver disease, underscoring the importance of prioritizing antiviral therapy for CHB in addition to addressing SLD.

Chronic hepatitis B (CHB) poses a major global public health challenge and is a leading cause of cirrhosis and liver cancer. Hepatic steatosis is common in individuals with CHB compared to the non-CHB population and is particularly prevalent in hepatitis B virus (HBV)-endemic regions, affecting about one-third of CHB patients. The interaction between hepatic steatosis and CHB-related disease progression is complex and still under debate. Evidence demonstrates that co-existing steatosis may worsen liver fibrosis while paradoxically increasing the likelihood of achieving better HBV control. In particular, despite the association of steatotic liver disease (SLD) with lower HBV viral loads and higher rates of HBsAg seroclearance, the coexistence of CHB and SLD can potentially accelerate liver disease progression. Factors such as fat deposition, lipotoxicity, oxidative stress, and chronic inflammation in SLD may foster a pro-fibrotic and pro-carcinogenic environment, accelerating the disease progression. Additionally, loss of global DNA methylation, changes in the immune microenvironment, and genetic susceptibility further contribute to the development of CHB-related cirrhosis and hepatocellular carcinoma (HCC). This review examines the mechanisms driving liver disease progression and the heightened risk of cirrhosis and HCC in patients with concurrent CHB and steatotic liver disease, underscoring the importance of prioritizing antiviral therapy for CHB in addition to addressing SLD.

Pharmacotranscriptomic profiles, which capture drug-induced changes in gene expression, offer vast potential for computational drug discovery and are widely used in modern medicine. However, current computational approaches neglected the associations within gene‒gene functional networks and unrevealed the systematic relationship between drug efficacy and the reversal effect. Here, we developed a new genome-scale functional module (GSFM) transformation framework to quantitatively evaluate drug efficacy for in silico drug discovery. GSFM employs four biologically interpretable quantifiers: GSFM_Up, GSFM_Down, GSFM_ssGSEA, and GSFM_TF to comprehensively evaluate the multi-dimension activities of each functional module (FM) at gene-level, pathway-level, and transcriptional regulatory network-level. Through a data transformation strategy, GSFM effectively converts noisy and potentially unreliable gene expression data into a more dependable FM active matrix, significantly outperforming other methods in terms of both robustness and accuracy. Besides, we found a positive correlation between RS_GSFM and drug efficacy, suggesting that RS_GSFM could serve as representative measure of drug efficacy. Furthermore, we identified WYE-354, perhexiline, and NTNCB as candidate therapeutic agents for the treatment of breast-invasive carcinoma, lung adenocarcinoma, and castration-resistant prostate cancer, respectively. The results from in vitro and in vivo experiments have validated that all identified compounds exhibit potent anti-tumor effects, providing proof-of-concept for our computational approach.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

JMJD1C (Jumonji Domain Containing 1C), a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with different genetic mutations, representing a therapeutic opportunity with broad application. Yet how JMJD1C regulates the leukemic programs of various AML cells is largely unexplored. Here we show that JMJD1C interacts with the master hematopoietic transcription factor RUNX1, which thereby recruits JMJD1C to the genome to facilitate a RUNX1-driven transcriptional program that supports leukemic cell survival. The underlying mechanism hinges on the long N-terminal disordered region of JMJD1C, which harbors two inseparable abilities: condensate formation and direct interaction with RUNX1. This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias.
Core Binding Factor Alpha 2 Subunit/genetics* ; Humans ; Leukemia, Myeloid, Acute/pathology* ; Jumonji Domain-Containing Histone Demethylases/chemistry* ; Gene Expression Regulation, Leukemic ; Oxidoreductases, N-Demethylating/genetics* ; Cell Line, Tumor

Objective: To understand trends and related factors influencing overweight and obesity among primary and secondary school students in Tianjin, so as to provide a basis for formulating overweight and obesity prevention and control strategies. Methods: In September of each year from 2019 to 2023, a survey was conducted among 197 707 primary and secondary school students in 16 districts of Tianjin through a stratified random cluster sampling method. Physical examination was carried out in accordance with the Technical Standard for Physical examination for Student, and overweight and obesity survey was carried out. Basic information, smoking, drinking, diet, physical exercise, and sleep status were collected through questionnaire surveys. Results: The detection rates of overweight and obesity among primary and secondary school students in Tianjin from 2019 to 2023 were 39.07%, 43.33%, 41.54%, 43.92%, and 40.24%, respectively，showing an increasing trend(χ2trend=7.96,P<0.01). The detection rates of overweight increased in both vocational high schools and suburban counties (χ2trends=9.08, 47.18, P<0.01). The detection rates of obesity increased among both male and female students, in primary and vocational high schools and suburban counties (χ2trends=108.34, 15.99, 7.32, 10.95, 14.75, P<0.01). Multivariate Logistic regression analysis showed that smoking, drinking, unhealthful diet, and lack of proper physical exercise had a higher risk of obesity among primary and secondary school students (OR=1.26, 1.13, 1.08, 1.21, P<0.05). Stratified analysis showed that the risk of obesity was higher among boys with unhealthful and moderate lifestyle habits, as well as primary school students with unhealthful lifestyle habits (OR=1.15, 1.11, 1.27, P<0.05). Boys, girls and primary school students with unhealthful lifestyle habits, girls and ordinary high school students with moderate lifestyle habits had higher risk of being overweight (OR=1.14, 1.32, 1.21, 1.18, 1.40, P<0.05). Conclusions The detection rates of overweight and obesity among primary and secondary school students in Tianjin shows an increasing trend. Comprehensive lifestyle should be implemented to better prevent and control the risk of overweight and obesity.

Objective: To investigate the tendency of obesity and depressive symptoms in middle school students in Tianjin, so as to provide a reference for exploring the clustering patterns of health risk behaviors and their effects on obesity and depressive symptoms. Methods: A stratified cluster sampling method was used to investigate the obesity, depressive symptoms and health risk behaviors of middle school students from 16 counties of Tianjin from 2019 to 2023. The latent classes analysis was used to classify health risk behaviors. The χ 2 test and Logistic regression were used to analyze the effects of different categories on obesity and depression symptoms. Results: The obesity detection rate of middle school students in Tianjin from 2019 to 2023 first increased ( 20.90% in 2019, 23.35% in 2020) and then decreased and gradually stabilized (2021-2023:22.20%-22.69%), and the detection rate of depressive symptoms showed a decreasing trend (from 21.65% to 14.92%). The detection rate of comorbidity of obesity and depressive symptoms first increased (4.62% in 2019, 4.66% in 2020) and then gradually decreased to 3.43% in 2023, and the rate was higher in boys than in girls and higher in urban areas than in suburban areas. Latent category analysis classified health risk behaviors into four categories: lack of exercise group, poor behaviors such as sleep group, poor diet group and healthy group. After adjusting for demographic characteristics,the results of Logistic regression analysis showed that the co-occurrence risk of obesity and depression symptoms among the top three groups of middle school students were 1.35( OR=1.35, 95%CI =1.15-1.58), 4.20( OR=4.20, 95%CI =3.50-5.04), and 1.84( OR=1.84, 95%CI =1.40-2.38)times, compared to the healthy group ( P <0.05). Conclusions From 2019 to 2023, the comorbidity rate of obesity and depression among middle school students in Tianjin increased first and then decreased gradually. Interventions should be made in the aspects of exercise, diet, sleep and other behaviors.

Objective:To search, screen and summarize the best evidence of screening and management of patients with post-stroke fatigue, and to provide basis for early identification of clinical staff.Methods:According to the "6S" pyramid model, the system searches for relevant evidence on post stroke fatigue screening and management from UpToDate, BMJ Best Practice, International Guidelines Collaboration Network, New Zealand Guidelines Collaboration Group, Ontario Registered Nurses Association website, Scottish Interhospital Guidelines Network, Joanna Briggs Institute Evidence Based Health Care Center database, and Yimaitong, National Stroke Foundation, Stroke Association, National Stroke Center, Cochrane Library, PubMed, Embase, CINAHL, CNKI, WanFang Datebase, VIP and CBM from January 2013 to March 2023 regarding screening and management of post stroke fatigue patients. Researchers screen literature, evaluate quality, and summarize evidence.Results:Fifteen articles were selected, including 1 clinical decision, 3 guidelines, 3 expert consensus, 2 evidence summary, 5 systematic review and 1 randomized controlled trial. A total of 22 best evidence items were summarized from seven aspects of screening assessment, risk factors, psychosocial intervention, activity and rest, health education, complementary therapy, and follow-up.Conclusions:The study summarized the best evidence for the screening and management of patients with post-stroke fatigue, so as to provide a more scientific and systematic approach to the management of post-stroke fatigue and provide a reference for improving the long-term quality of life of stroke patients.

Objective To investigate the genetic association between nonalcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM)using bidirectional two-sample Mendelian randomization(MR),as well as the causal relationship between NAFLD and T2DM across different body mass index(BMI)categories.Methods The data were derived from genome-wide association studies conducted in European populations,with a sample size of 32 941 cases for NAFLD,312 646 cases for T2DM,and 681 275 cases for BMI.The univariate and multivariate MR methods were used to assess the bidirectional causal relationship between NAFLD and T2DM in the general population and across different BMI subtypes.The methods of inverse-variance weighting,MR-Egger regression,constrained maximum likelihood and model averaging,and weighted median were used to conduct the MR analysis,and MR-Pleiotropy Residual Sum and Outlier,radial MR,the MR-Egger intercept method,and the Cochrane Q test were used for sensitivity analysis.Results The univariate MR analysis revealed a bidirectional causal relationship between NAFLD and T2DM in the general population(forward analysis:odds ratio[OR]=9.75,95%confidence interval[CI]:2.57-37.00,P＜0.001;reverse analysis:OR=1.01,95%CI:1.00-1.01,P＜0.01).After adjustment for BMI,the multivariate MR analysis showed that the causal relationship between NAFLD and T2DM remained significant in the general population(OR=33.12,95%CI:7.57-144.95,P＜0.000 1).The subgroup analysis showed a causal relationship between NAFLD and T2DM across all BMI subtypes(lean subgroup:OR=12.19,95%CI:3.35-44.40,P＜0.001;overweight subgroup:OR=4.30,95%CI:1.69-10.92,P＜0.01;obese subgroup:OR=1.67,95%CI:1.14-2.44,P＜0.01).Conclusion This study reveals the causal relationship between NAFLD and T2DM in the general population of NAFLD and across different BMI subtypes from a genetic perspective.