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 explore the mechanism by which soybean isoflavone(SI)reduces calcium overload induced by cerebral ischemia-reperfusion(I/R).Methods Forty-eight SD rats were randomized into 4 groups to receive sham operation,cerebral middle artery occlusion for 2 h followed by 24 h of reperfusion(I/R model group),or injection of adeno-associated virus carrying Frizzled-2 siRNA or empty viral vector into the lateral cerebral ventricle after modeling.Western blotting was used to examine Frizzled-2 knockdown efficiency and changes in protein expressions in the Wnt/Ca2+signaling pathway.Calcium levels and pathological changes in the ischemic penumbra(IP)were measured using calcium chromogenic assay and HE staining,respectively.Another 72 SD randomly allocated for sham operation,I/R modeling,or soy isoflavones pretreatment before modeling were examined for regional cerebral blood flow using a Doppler flowmeter,and the cerebral infarct volume was assessed using TTC staining.Pathologies in the IP area were evaluated using HE and Nissl staining,and ROS level,Ca2+level,cell apoptosis,and intracellular calcium concentration were analyzed using immunofluorescence assay or flow cytometry;the protein expressions of Wnt5a,Frizzled-2,and P-CaMK II in the IP were detected with Western blotting and immunohistochemistry.Results In rats with cerebral I/R,Frizzled-2 knockdown significantly lowered calcium concentration(P<0.001)and the expression levels of Wnt5a,Frizzled-2,and P-CaMK II in the IP area.In soy isoflavones-pretreated rats,calcium concentration,ROS and MDA levels,cell apoptosis rate,cerebral infarct volume,and expression levels of Wnt/Ca2+signaling pathway-related proteins were all significantly lower while SOD level was higher than those in rats in I/R model group.Conclusion Soy isoflavones can mitigate calcium overload in rats with cerebral I/R by inhibiting the Wnt/Ca2+signaling pathway.

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.

From the perspectives of traditional Chinese medicine （TCM） information knowledge base and assisted decision-making knowledge base， the construction status， quality evaluation status and existing problems of current TCM knowledge bases have been sorted out. And based on the quality evaluation strategies and dimensions of know-ledge bases in other disciplines， the evaluation indexes for TCM knowledge base is discussed， and the evaluation framework is initially formed， providing ideas for the improvement of the TCM knowledge base evaluation system. In terms of the evaluation indexes， there are basic evaluation dimensions which include data sources， data collection， and data application. The specific evaluation dimension of the information-based knowledge base is data quality， while that of the assisted decision-making knowledge base is data matching. Except for the data application dimension which counts the valid data items in the database for calculation， other indexes are scored based on the qualitative evaluation of "yes"， "no" or "unknown". The basic evaluation score and the specific evaluation score are added to obtain the total score. The knowledge base is graded according to the score， and the results are presented in the form of grade plus number.

Objective: To investigate the comorbidity of myopia and scoliosis among primary and secondary school students in Tianjin, and to analyze the school environment risk factors contributing to these health issues, so as to provide a scientific basis for development effective prevention measures. Methods: A total of 41 654 primary and secondary school students from 16 districts of Tianjin were selected by stratified random cluster sampling from September to October 2023 to screen for myopia and scoliosis. Univariate analysis was performed to examine the data, followed by a bivariate multivariate Logistic regression model and cumulative effect analysis to explore the influencing factors of their comorbidity. Results: In 2023, the prevalence of comorbidity of screening positive myopia and scoliosis among primary and secondary school students in Tianjin was 2.65%. The prevalence was higher in suburban areas (3.26%) compared to urban areas (2.02%), higher among females (3.81%) compared to males (1.59%), and highest in high school students (6.17%) compared to middle school (4.19%) and primary school students (0.44%) (χ2=62.23, 198.69, 953.19, P<0.01). Logistic regression analysis showed that the number of physical education classes ≥3 per week, the number of eye health exercises at school ≥2 per day, outdoor activities between classes, teachers reminding to pay attention to reading and writing posture and strict eye standing posture were negatively correlated with the comorbidity of screening positive myopia and scoliosis (OR=0.66, 0.77, 0.71, 0.78, 0.74, P<0.05). Reading or electronic screen while lying or lying on the stomach was positively associated with the comorbidity of screening positive myopia and scoliosis (OR=1.77, P<0.05). Cumulative effect analysis showed that the cumulative score (4-7, 7-9, ≥10) was negatively correlated with the comorbidity of screening positive of myopia and scoliosis (OR=0.65, 0.55, 0.52, P<0.05). Conclusions The school environment support and students personal behavior habits in school are related to the comorbidity of comorbidity of screening positive myopia and scoliosis. Prevention and control of myopia and scoliosis should improve the environmental factors related to students health in school.