AGRP Neurons Project to the Medial Preoptic Area and Modulate Maternal Nest-Building.

AGRP (agouti-related neuropeptide) expressing inhibitory neurons sense caloric needs of an animal to coordinate homeostatic feeding. Recent evidence suggests that AGRP neurons also suppress competing actions and motivations to mediate adaptive behavioral selection during starvation. Here, in adult mice of both sexes we show that AGRP neurons form inhibitory synapses onto ∼30% neurons in the medial preoptic area (mPOA), a region critical for maternal care. Remarkably, optogenetically stimulating AGRP neurons decreases maternal nest-building while minimally affecting pup retrieval, partly recapitulating suppression of maternal behaviors during food restriction. In parallel, optogenetically stimulating AGRP projections to the mPOA or to the paraventricular nucleus of hypothalamus but not to the LHA (lateral hypothalamus area) similarly decreases maternal nest-building. Chemogenetic inhibition of mPOA neurons that express Vgat (vesicular GABA transporter), the population targeted by AGRP terminals, also decreases maternal nest-building. In comparison, chemogenetic inhibition of neurons in the LHA that express vesicular glutamate transporter 2, another hypothalamic neuronal population critical for feeding and innate drives, is ineffective. Importantly, nest-building during low temperature thermal challenge is not affected by optogenetic stimulation of AGRP→mPOA projections. Finally, via optogenetic activation and inhibition we show that distinctive subsets of mPOA Vgat+ neurons likely underlie pup retrieval and maternal nest-building. Together, these results show that AGRP neurons can modulate maternal nest-building, in part through direct projections to the mPOA. This study corroborates other recent discoveries and underscores the broad functions that AGRP neurons play in antagonizing rivalry motivations to modulate behavioral outputs during hunger.SIGNIFICANCE STATEMENT In order for animals to initiate ethologically appropriate behaviors, they must typically decide between behavioral repertoires driven by multiple and often conflicting internal states. How neural pathways underlying individual behaviors interact to coherently modulate behavioral outputs, in particular to achieve a proper balance between behaviors that serve immediate individual needs versus those that benefit the propagation of the species, remains poorly understood. Here, by investigating projections from a neuronal population known to drive hunger behaviors to a brain region critical for maternal care, we show that activation of AGRP→mPOA projections in females dramatically inhibits maternal nest-building while leaving mostly intact pup retrieval behavior. Our findings shed new light on neural organization of behaviors and neural mechanisms that coordinate behavioral selection.

[Meta-analysis of Yinzhihuang oral liquid in treatment of intrahepatic cholestasis of pregnancy].

To systematically review the clinical efficacy and safety of Yinzhihuang oral liquid in the treatment of intrahepatic cholestasis of pregnancy(ICP). Literatures published by June 2016 were searched in databases, such as Medline, Pubmed, Cochrane Library, China National Knowledge Infrastructure(CNKI), Chinese Scientific Journals Full-text Database(VIP), Chinese biomedical literature database(CBM), and Wanfang Database. Randomized controlled trials(RCT) of Yinzhihuang oral liquid were collected according to the inclusion criteria, and the methodological quality of selected literatures was evaluated. The Meta-analysis was conducted by using RevMan 5.3 software. A total of 7 RCTs involving 711 patients were included. The results of Meta-analysis showed that, compared with control group, Yinzhihuang oral liquid significantly alleviated pruritus symptoms[MD=－0.68, 95%CI(－0.95,－041), P<0.000 01], reduced blood biochemical indexes including TBA[MD=－7.23, 95%CI (－10.88,－3.58), P=0.000 1], TB[MD=－1.90, 95%CI(－3.09,－0.70), P=0.002], ALT[MD=－39.08, 95%CI (－56.46,－21.70), P<0.000 1], and CG [MD=－0.71, 95%CI(－0.89,－0.52), P<0.000 01]. In the respect of pregnancy outcome, Yinzhihuang oral liquid can distinctly improve birth weight [MD=430.03, 95%CI (219.28, 640.78), P<0.000 1]. However, there was no significant difference in cesarean section rate [OR=0.93, 95%CI (0.36, 2.36), P=0.87], preterm birth rates [OR=0.63, 95%CI (0.28, 1.42), P=0.26], and neonatal asphyxia rate [OR=0.50, 95%CI (0.18, 1.43), P=0.20]. Yinzhihuang oral liquid showed better efficiency and slighter adverse reaction. However, more rigorously designed, double-blind, randomized controlled trials with large sample size and high quality are required to provide further evidences.

PKD regulates mitophagy to prevent oxidative stress and mitochondrial dysfunction during mouse oocyte maturation.

Mitochondria play dominant roles in various cellular processes such as energy production, apoptosis, calcium homeostasis, and oxidation-reduction balance. Maintaining mitochondrial quality through mitophagy is essential, especially as its impairment leads to the accumulation of dysfunctional mitochondria in aging oocytes. Our previous research revealed that PKD expression decreases in aging oocytes, and its inhibition negatively impacts oocyte quality. Given PKD's role in autophagy mechanisms, this study investigates whether PKD regulates mitophagy to maintain mitochondrial function and support oocyte maturation. When fully grown oocytes were treated with CID755673, a potent PKD inhibitor, we observed meiosis arrest at the metaphase I stage, along with decreased spindle stability. Our results demonstrate an association with mitochondrial dysfunction, including reduced ATP production and fluctuations in Ca2+ homeostasis, which ultimately lead to increased ROS accumulation, stimulating oxidative stress-induced apoptosis and DNA damage. Further research has revealed that these phenomena result from PKD inhibition, which affects the phosphorylation of ULK, thereby reducing autophagy levels. Additionally, PKD inhibition leads to decreased Parkin expression, which directly and negatively affects mitophagy. These defects result in the accumulation of damaged mitochondria in oocytes, which is the primary cause of mitochondrial dysfunction. Taken together, these findings suggest that PKD regulates mitophagy to support mitochondrial function and mouse oocyte maturation, offering insights into potential targets for improving oocyte quality and addressing mitochondrial-related diseases in aging females.

Harnessing the potential of long non-coding RNAs in breast cancer: from etiology to treatment resistance and clinical applications.

Breast cancer (BC) is the most common malignancy among women and a leading cause of cancer-related deaths of females worldwide. It is a complex and molecularly heterogeneous disease, with various subtypes that require different treatment strategies. Despite advances in high-resolution single-cell and multinomial technologies, distant metastasis and therapeutic resistance remain major challenges for BC treatment. Long non-coding RNAs (lncRNAs) are non-coding RNAs with more than 200 nucleotides in length. They act as competing endogenous RNAs (ceRNAs) to regulate post-transcriptional gene stability and modulate protein-protein, protein-DNA, and protein-RNA interactions to regulate various biological processes. Emerging evidence suggests that lncRNAs play essential roles in human cancers, including BC. In this review, we focus on the roles and mechanisms of lncRNAs in BC progression, metastasis, and treatment resistance, and discuss their potential value as therapeutic targets. Specifically, we summarize how lncRNAs are involved in the initiation and progression of BC, as well as their roles in metastasis and the development of therapeutic resistance. We also recapitulate the potential of lncRNAs as diagnostic biomarkers and discuss their potential use in personalized medicine. Finally, we provide lncRNA-based strategies to promote the prognosis of breast cancer patients in clinical settings, including the development of novel lncRNA-targeted therapies.

Secure State Estimation of Nonlinear Cyber-Physical Systems Against DoS Attacks: A Multiobserver Approach.

This article focuses on the problem of secure state estimation for cyber-physical systems (CPSs), whose physical plants are modeled as nonlinear strict-feedback systems. The measured output is sent to the designed observer over a wireless communication network subject to denial-of-service (DoS) attacks. Due to the energy constraints of the attackers, the attack duration is upper bounded. Under DoS attacks, the transmission is prevented, which worsens the estimation accuracy of the existing nonlinear observers significantly. To maintain the estimation performance, a novel multiobserver scheme and a switched algorithm are proposed by introducing the hold-input mechanism and the cascade observer technique. In comparison to the existing results, where the estimation error systems may be unstable during the attack time interval, the estimation error of the designed observer converges exponentially, such that the estimation performance is improved effectively. Finally, the theoretical findings are illustrated by simulation results.

Sexually dimorphic effects of estrogen receptor 2 deletion in the dorsal raphe nucleus on emotional behaviors.

Sex differences in emotional behaviors and affective disorders have been widely noted, of which sexually dimorphic secretion of gonadal steroid hormones such as estrogen is suspected to play a role. However, the underlying neural mechanisms remain poorly understood. We noted that the expression of estrogen receptor 2 (Esr2, or ERß), a key mediator of estrogen signaling in the brain, was enriched in the dorsal raphe nucleus (DRN), a region involved in emotion regulation. To investigate whether DRN Esr2 expression confers sex-specific susceptibility or vulnerability in emotional behaviors, we generated a conditional allele of Esr2 that allowed for site-specific deletion of Esr2 in the DRN via local injection of Cre-expressing viruses. DRN-specific Esr2 deletion mildly increased anxiety behaviors in females, as shown by decreased time spent in the center zone of an open field in knockout females. By contrast, DRN Esr2 deletion had no effects on anxiety levels in males, as demonstrated by knockout males spending comparable time in the center zone of an open field and open arms of an elevated-plus maze. Furthermore, in the tail suspension test, DRN Esr2 deletion reduced immobility, a depression-like behavior, in a male-biased manner. Together, these results reveal sex-specific functions of DRN Esr2 in regulating emotional behaviors and suggest targeted manipulation of DRN Esr2 signaling as a potential therapeutic strategy to treat sex-biased affective disorders.

Prognostic value of T cell immunoglobulin and mucin-domain containing-3 expression in upper gastrointestinal tract tumors: A meta-analysis.

BACKGROUND: There is a lack of robust prognostic markers for upper gastrointestinal (GI) tract cancers, including esophageal, gastric, and esophagogastric junction cancers. T cell immunoglobulin and mucin-domain containing-3 (TIM3) plays a key immunomodulatory role and is linked to the prognosis of various cancers. However, the significance of TIM3 in upper GI tract tumors is still uncertain. AIM: To investigate the prognostic value of TIM3 expression in upper GI tract tumors. METHODS: A literature search was conducted on the PubMed, Embase, and Web of Science databases for relevant studies published until June 2023. After screening and quality assessment, studies that met the criteria were included in the meta-analysis. Statistical methods were used for the pooled analysis to assess the association of TIM3 expression in upper GI tract tumors with the prognosis and clinicopathological parameters. The results were reported with the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Nine studies involving 2556 patients with upper GI tract cancer were included. High TIM3 expression was associated with a worse prognosis in upper GI tract cancer (HR: 1.17, 95%CI: 1.01-1.36). Positive expression of TIM3 in gastric cancer was correlated with the T and N stage, but the difference was not statistically significant. However, TIM3 overexpression was significantly correlated with the TNM stage (odds ratio: 1.21, 95%CI: 0.63-2.33; P < 0.05). TIM3 expression showed no association with the other clinicopathological parameters. CONCLUSION: High expression of TIM3 in the upper GI tract cancer is associated with a worse prognosis and advanced T or N stages, indicating its potential value as a prognostic biomarker. These findings may provide a basis for the personalized treatment of upper GI tract cancers.

Secure State Estimation With Switched Compensation Mechanism Against DoS Attacks.

This article is concerned with the secure state estimation problem for cyber-physical systems under intermittent denial-of-service (DoS) attacks. Based on a switching scheme and the cascade observer technique, a novel resilient state observer with a switched compensation mechanism is designed. Moreover, a quantitative relationship between the resilience against DoS attacks and the design parameters is revealed. Compared with the existing results, where only the boundedness of the estimation error is guaranteed under DoS attacks, the exponential convergence of the estimation error is achieved by employing the proposed observer scheme, such that the estimation performance is improved. More specifically, in the disturbance-free case, it is proven that the state estimation error converges exponentially to 0 despite the existence of DoS attacks. Finally, simulation results are provided to illustrate the effectiveness and merits of the proposed methods.

Design and synthesis of marine sesterterpene analogues as novel estrogen receptor α degraders for breast cancer treatment.

Targeted protein degradation using small molecules is an intriguing strategy for drug development. The marine sesterterpene compound MHO7 had been reported to be a potential ERα degradation agent. In order to further improve its biological activity, two series of novel MHO7 derivatives with long side chains were designed and identified as novel selective estrogen receptor down-regulators (SERDs). The growth inhibition activity of the novel SERD compounds were significantly affected by the type and length of the side chain. Most of the derivatives were significantly more potent than MHO7 against both drug-sensitive and drug-resistant breast cancer cells. Among them, compound 16a, with IC50 values of 0.41 µM against MCF-7 cell lines and 9.6-fold stronger than MHO7, was the most potential molecule. A whole-genome transcriptomic analysis of MCF-7 cells revealed that the mechanism of 16a against MCF-7 cell was similar with that of MHO7. The estrogen signaling pathway was the most affected among the disturbed genes, but the ERα degradation activity of 16a was observed higher than that of MHO7. Other effects of 16a were confirmed similar with MHO7, which means that the basic mechanisms of the derivatives are the same with the ophiobolin backbone, i.e. the degradation of ERα is mediated via proteasome-mediated process, the induction of apoptosis and the cell cycle arrest at the G1 phase. Meanwhile, a decrease of mitochondrial membrane potential and an increase of cellular ROS were also detected. Based on these results, as a novel modified ophiobolin derived compound, 16a may warrant further exploitation as a promising SERD candidate agent for the treatment of breast cancer.

Synthesis and structure-activity relationship study of a potent MHO7 analogue as potential anti-triple negative breast cancer agent.

Triple-negative breast cancer (TNBC) is the most aggressive, high recurrence and metastatic breast cancer subtype. There are few safe and effective therapeutic drugs for treatment of TNBC. The marine natural product MHO7 has been determined to be a potential antitumor agent. However, its moderate activity and complex structure hampered its clinical application. In this study, a series of novel derivatives with modification on C24 of MHO7 were first synthesized. Some of the analogues were significantly more potent than MHO7 against all selected breast cancer cell lines. Among them, compound 4m had the best activity, and its IC50 value against TNBC was up to 0.51 µM. A whole-genome transcriptomic analysis shown that the mechanism of compound 4m against TNBC cells was similar with that of parent compound MHO7. Subsequent cellular mechanism studies showed that compound 4m could induce apoptosis of MDA-MB-231 cells through mitochondria pathway and cause G1 phase arrest. Moreover, 4m could disrupt the expressions of MAPK/Akt pathway-associated proteins (p-p38 and p-Akt) and remarkably increase the ratio of Bax to Bcl-2 and activate cleaved caspase 3/9/PARP. Importantly, 4m could influence the expression of Smad 7, and p-Smad 3 to inhibit TNBC cells metastasis. Stability assays in rat plasma and liver microsomes indicated that 4m still have room for further optimization. And the results of the online molinspiration software predicted that 4m has desirable physicochemical properties but some properties still have violation from the Lipinski rule of five. Overall, the modification on C24 of MHO7 was a promising way for developing novel anti-TNBC agents with considerable potential for optimization.

A circuit from the ventral subiculum to anterior hypothalamic nucleus GABAergic neurons essential for anxiety-like behavioral avoidance.

Behavioral observations suggest a connection between anxiety and predator defense, but the underlying neural mechanisms remain unclear. Here we examine the role of the anterior hypothalamic nucleus (AHN), a node in the predator defense network, in anxiety-like behaviors. By in vivo recordings in male mice, we find that activity of AHN GABAergic (AHNVgat+) neurons shows individually stable increases when animals approach unfamiliar objects in an open field (OF) or when they explore the open-arm of an elevated plus-maze (EPM). Moreover, object-evoked AHN activity overlap with predator cue responses and correlate with the object and open-arm avoidance. Crucially, exploration-triggered optogenetic inhibition of AHNVgat+ neurons reduces object and open-arm avoidance. Furthermore, retrograde viral tracing identifies the ventral subiculum (vSub) of the hippocampal formation as a significant input to AHNVgat+ neurons in driving avoidance behaviors in anxiogenic situations. Thus, convergent activation of AHNVgat+ neurons serves as a shared mechanism between anxiety and predator defense to promote behavioral avoidance.

Fibroblast A20 governs fibrosis susceptibility and its repression by DREAM promotes fibrosis in multiple organs.

In addition to autoimmune and inflammatory diseases, variants of the TNFAIP3 gene encoding the ubiquitin-editing enzyme A20 are also associated with fibrosis in systemic sclerosis (SSc). However, it remains unclear how genetic factors contribute to SSc pathogenesis, and which cell types drive the disease due to SSc-specific genetic alterations. We therefore characterize the expression, function, and role of A20, and its negative transcriptional regulator DREAM, in patients with SSc and disease models. Levels of A20 are significantly reduced in SSc skin and lungs, while DREAM is elevated. In isolated fibroblasts, A20 mitigates ex vivo profibrotic responses. Mice haploinsufficient for A20, or harboring fibroblasts-specific A20 deletion, recapitulate major pathological features of SSc, whereas DREAM-null mice with elevated A20 expression are protected. In DREAM-null fibroblasts, TGF-ß induces the expression of A20, compared to wild-type fibroblasts. An anti-fibrotic small molecule targeting cellular adiponectin receptors stimulates A20 expression in vitro in wild-type but not A20-deficient fibroblasts and in bleomycin-treated mice. Thus, A20 has a novel cell-intrinsic function in restraining fibroblast activation, and together with DREAM, constitutes a critical regulatory network governing the fibrotic process in SSc. A20 and DREAM represent novel druggable targets for fibrosis therapy.

A solution-processed ternary copper halide thin films for air-stable and deep-ultraviolet-sensitive photodetector.

Recently, the newly emerging lead-halide perovskites have received tremendous attention in the photodetection field because of their intrinsic large light absorption and high well-balanced carrier transport characteristics. Unfortunately, the issue of instability and the existence of toxic lead cations have greatly restricted their practical applications and future commercialization. Furthermore, the previous studies on perovskite photodetectors mainly operate in visible and near-infrared light region, and there are practically no relevant reports aimed at the deep-ultraviolet (DUV) region. In this study, an air-stable and DUV-sensitive photoconductive detector was demonstrated with a solution-processed ternary copper halides Cs3Cu2I5 thin films as the light absorber. The proposed photodetector is very sensitive to wavelengths of light below 320 nm and unresponsive to the visible light. Because of the high material integrity and large surface coverage of the Cs3Cu2I5 thin films, the detector presents an outstanding photodetection performance with a photoresponsivity of ∼17.8 A W-1, specific detectivity of 1.12 × 1012 Jones, and fast response speed of 465/897 µs, superior to previously reported DUV photodetectors based on other material systems. Unlike traditional lead-halide perovskites, the lead-free Cs3Cu2I5 shows remarkable stability against heat, UV light, and environmental oxygen/moisture. Thus, the unsealed photodetector demonstrates good operation stability for 11 h of continuous running in open air. Even after 80-day storage in ambient air, its photodetection capability can nearly be maintained. The results suggest that non-toxic Cs3Cu2I5 could be a potential candidate for stable and environment friendly DUV detectors, enabling an assembly of optoelectronic systems in the future.

Specific Hypothalamic Neurons Required for Sensing Conspecific Male Cues Relevant to Inter-male Aggression.

The hypothalamus regulates innate social interactions, but how hypothalamic neurons transduce sex-related sensory signals emitted by conspecifics to trigger appropriate behaviors remains unclear. Here, we addressed this issue by identifying specific hypothalamic neurons required for sensing conspecific male cues relevant to inter-male aggression. By in vivo recording of neuronal activities in behaving mice, we showed that neurons expressing dopamine transporter (DAT+) in the ventral premammillary nucleus (PMv) of the hypothalamus responded to male urine cues in a vomeronasal organ (VNO)-dependent manner in naive males. Retrograde trans-synaptic tracing further revealed a specific group of neurons in the bed nucleus of the stria terminalis (BNST) that convey male-relevant signals from VNO to PMv. Inhibition of PMvDAT+ neurons abolished the preference for male urine cues and reduced inter-male attacks, while activation of these neurons promoted urine marking and aggression. Thus, PMvDAT+ neurons exemplify a hypothalamic node that transforms sex-related chemo-signals into recognition and behaviors.

Adaptive Fault Estimation for T-S Fuzzy Interconnected Systems Based on Persistent Excitation Condition via Reference Signals.

This paper is concerned with the fault estimation (FE) problem for a class of interconnected nonlinear systems described by Takagi-Sugeno fuzzy models. Different from the existing FE approaches, where the reference inputs are always viewed as external disturbances, the considered reference signals are injected directly in the controller to excite the system states to ensure persistent excitation condition. Within this framework, a bank of distributed adaptive observers are then designed to effectively estimate the actuator fault parameters even in the presence of nonlinear interconnections. Moreover, in the disturbance-free case, by employing graph theory, a global Lyapunov function is constructed such that the corresponding fault parameter estimate errors are proved to be asymptotically convergent provided that the interconnected strengths are less than a given constant. Finally, two simulation examples are provided to demonstrate the validity of the presented FE scheme.

The expressions and significance of B7-H3 and CTLA-4 in the clinical stages of non-small-cell lung cancer.

The aim of this study was to analyze the expressions and significance of B7-H3 and CTLA-4 in the clinical stages of non-small-cell lung cancer (NSCLC). Seventy patients with NSCLC who underwent surgical resection or biopsy between January 2016 and February 2018 were enrolled. Among them, 30 were cases of paracancerous tissues and were assigned to the control group (CON). These cases were analyzed using immunochemical methods. Of the 70 cases, 48 were of adenocarcinoma, 19 were of squamous cell carcinoma, and 3 were of adenosquamous carcinoma. The expression rates of B7-H3 and CTLA-4 in the observation group (OBS) were 64.2% and 57.1% respectively, and those in the CON group were 6.7% and 0%, respectively (χ2=27.988, 28.571, P<0.001). The expression levels of B7-H3 and CTLA-4 in patients with poor differentiation, in stages III-IV, or with lymph node metastasis were significantly higher than those in patients with good-to-moderate differentiation, in stages I-II, and without lymph node metastasis (P<0.05). There was a positive correlation between the expressions of B7-H3 and CTLA-4 in the OBS group (r=0.74, P<0.05). B7-H3 and CTLA-4 are highly expressed and positively correlated with each other in NSCLC patients and are also closely related to clinical stages.

Association between B vitamins and schizophrenia: A population-based case-control study.

To explore the association between schizophrenia and six types of B vitamins, including choline, biotin, riboflavin, pyridoxamine, pyridoxine and nicotinamide, based on the hydrophilic interaction liquid chromatography column (HILIC) Liquid Chromatography-Mass Spectrometry (LC-MS) platform. We conducted the case-control study between November 2015 and September 2016 in Weifang, Shandong Province, China. Blood samples from 128 cases of schizophrenia and 101 controls were collected, and B vitamin were measured by LC-MS coupled with HILIC. The HILIC UPLC-MS based analysis of serum B vitamins levels from 128 cases (30 cases with first-episode, 98 cases with relapse) and 101 controls were performed. The results indicated that lower pyridoxine level and schizophrenia was related. (total cases versus controls: ß= -0.215, 95% CI: -0.271, -0.125, p < 0.001; first-episode cases versus controls: ß = -0.190, 95% CI: -0.277, -0.103, p < 0.001). Higher nicotinamide level was also associated with schizophrenia after adjusting confounders (ß = 0.343, 95% CI: 0.022, 0.664, p = 0.036). Other four B vitamins, including biotin, riboflavin, pridoxamine and choline, were showed no statistically difference in cases versus controls, first episode cases versus relapse cases. Two types of B Vitamins, pyridoxine and nicotinamide, show significant association with the schizophrenia.

Clinical features of acute hepatitis E super-infections on chronic hepatitis B.

AIM: To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B (CHB) superimposed with hepatitis E virus (HEV). METHODS: This retrospective cohort study included 228 patients with acute HEV infection (showing clinical acute hepatitis symptomology and positivity for anti-HEV immunoglobulin M) with underlying CHB (confirmed by positivity for hepatitis B surface antigen and/or hepatitis B virus (HBV) DNA over 6 mo) who had been admitted to the Shanghai Public Health Clinical Center, which represents the regional tertiary hospital for infectious diseases in Shanghai city, China. Data for adverse outcomes were collected, and included severe liver diseases (defined as liver failure and/or acute liver decompensation) and liver-related mortality. Logistic regression modeling was performed to determine the risk factors for adverse outcomes. RESULTS: The symptoms caused by superimposed acute hepatitis E (AHE) were much more severe in cirrhotic patients (n = 94) than in non-cirrhotic patients (n = 134), as evidenced by significantly higher liver complications (77.7% vs 28.4%, P < 0.001) and mortality rate (21.3% vs 7.5%, P = 0.002). Most of the cirrhotic patients (n = 85, 90.4%) had no prior decompensation. Among the non-cirrhotic patients, superimposed AHE caused progressively more severe diseases that corresponded with the CHB disease stages, from immune tolerant to immune reactivation phases. Few risk factors were identified in the cirrhotic patients, but risk factors for non-cirrhotic patients were found to be intermediate HBV DNA levels (OR: 5.1, P = 0.012), alcohol consumption (OR: 6.4, P = 0.020), and underlying diabetes (OR: 7.5, P = 0.003) and kidney diseases (OR: 12.7, P = 0.005). Only 28.7% of the cirrhotic patients and 9.0% of the non-cirrhotic patients had received anti-HBV therapy previously and, in all cases, the efficacy had been suboptimal. CONCLUSION: CHB-related cirrhosis and intermediate HBV DNA level were associated with severe disease in superinfected patients, and successful antiviral treatment might counter this outcome.