Implementing the information system for older adult patients post-discharge self-management: a qualitative study.

BACKGROUND: Discharging older adult patients from the hospital poses risks due to their vulnerable conditions, complex instructions and limited health literacy. Insufficient information about medication side effects adds to patient concerns. To address this, a post-discharge information summary system was developed. While it has shown positive impacts, concerns exist regarding implementation fidelity. OBJECTIVE: This study employed a theory-driven approach to understand health providers' perspectives on effective implementation. METHOD: Individual semi-structured interviews were conducted via telephone with nurses, doctors and pharmacists from local public hospitals. All interviews were audio-recorded and transcribed verbatim. Theoretical Domains Framework (TDF) was applied for direct content analysis. Belief statements were generated by thematic synthesis under each of the TDF domains. RESULTS: A total of 98 participants were interviewed. Out of the 49 belief statements covering eight TDF domains, 19 were determined to be highly relevant to the implementation of the post-discharge information summary system. These TDF domains include knowledge, skills, social/professional role and identity, beliefs about consequences, intentions, memory, attention and decision processes, environmental context and resources and social influences. CONCLUSION: Our study contributes to the understanding of determinants in implementing discharge interventions for older adult patients' self-care. Our findings can inform tailored strategies for frontline staff, including aligning programme rationale with stakeholders, promoting staff engagement through co-creation, reinforcing positive programme outcomes and creating default settings. Future research should employ rigorous quantitative designs to examine the actual impact and relationships among these determinants.

Altered human gut virome in patients undergoing antibiotics therapy for Helicobacter pylori.

Transient gut microbiota alterations have been reported after antibiotic therapy for Helicobacter pylori. However, alteration in the gut virome after H. pylori eradication remains uncertain. Here, we apply metagenomic sequencing to fecal samples of 44 H. pylori-infected patients at baseline, 6-week (N = 44), and 6-month (N = 33) after treatment. Following H. pylori eradication, we discover contraction of the gut virome diversity, separation of virome community with increased community difference, and shifting towards a higher proportion of core virus. While the gut microbiota is altered at 6-week and restored at 6-month, the virome community shows contraction till 6-month after the treatment with enhanced phage-bacteria interactions at 6-week. Multiple courses of antibiotic treatments further lead to lower virus community diversity when compared with treatment naive patients. Our results demonstrate that H. pylori eradication therapies not only result in transient alteration in gut microbiota but also significantly alter the previously less known gut virome community.

A nomogram based on ultrasound radiomics for predicting the invasiveness of cN0 single papillary thyroid microcarcinoma.

Background: Up to 15.3% of papillary thyroid microcarcinoma (PTMC) patients with negative clinical lymph node metastasis (cN0) were confirmed to have pathological lymph node metastasis in level VI. Conventional ultrasound (US) focuses on the characteristics of tumor capsule and the periphery to determine whether the tumor has invasive growth. However, due to its small size, the typical features of invasiveness shown by conventional 2-dimensional (2D) US are not well visualized. US-based radiomics makes use of artificial intelligence and big data to build a model that can help improving diagnostic accuracy and providing prognostic implication of the disease. We hope to establish and assess the value of a nomogram based on US radiomics combined with independent risk factors in predicting the invasiveness of a single PTMC without clinical lymph node metastasis (cN0). Methods: A total of 317 patients with cN0 single PTMC who underwent US examination and operation were included in this retrospective cohort study. Patients were randomly divided into training and testing set in the ratio of 8:2. The US images of all patients were segmented, and the radiomics features were extracted. In the training dataset, the US with features of minimum redundancy maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) were selected and radiomics signatures were then established according to their respective weighting coefficients. Univariate and multivariate logistic regression analyses were employed to generate the risk factors of possible invasive PTMC. The nomogram is then made by combining high risk factors and the radiomics signature. The efficiency of the nomogram was evaluated by the receiver operating characteristic (ROC) curve and calibration curve, and its clinical application value was assessed by decision curve analysis (DCA). The testing dataset was used to validate the model. Results: In the model, seven radiomics features were selected to establish the radiomics signature. A nomogram was made by incorporating clinically independent risk factors and the radiomics signature. Both the ROC curve and calibration curve showed good prediction efficiency. The area under the curve (AUC), accuracy, sensitivity, and specificity of the nomogram in the training data were 0.76 [95% confidence interval (CI): 0.71-0.82], 0.811, 0.914, and 0.727, respectively whereas the results of the testing dataset were 0.71 (95% CI: 0.58-0.84), 0.841, 0.533, and 0.868. As such, the efficacy of the nomogram in predicting the invasiveness of PTMC was subsequently validated by the DCA. Conclusions: Nomogram based on thyroid US radiomics has an excellent predictive value of the potential invasiveness of a single PTMC without clinical lymph node metastasis. With these promising results, it can potentially be the imaging marker used in daily clinical practice.

Genomic characteristics and viral load dynamics of a SARS-CoV-2 Omicron BA.2.2 variant from a hospitalized patient treated with molnupiravir.

We sequenced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from nasal and throat swabs of a hospitalized patient during the fifth wave of coronavirus disease 2019 (COVID-19) pandemic in Hong Kong. Genomic characteristics and viral load dynamics of an Omicron BA.2.2 variant before and after molnupiravir treatment were presented.

T cells: Friends and foes in NASH pathogenesis and hepatocarcinogenesis.

In association with the pandemic spreading of obesity and metabolic syndrome, the prevalence of NAFLD-related HCC is increasing almost exponentially. In recent years, many of the underlining multifactorial causes of NAFLD have been identified, and the cellular mechanisms sustaining disease development have been dissected up to the single-cell level. However, there is still an urgent need to provide clinicians with more therapeutic targets, with particular attention on NAFLD-induced HCC, where immune checkpoint inhibitors do not work as efficiently. Whereas much effort has been invested in elucidating the role of innate immune response in the hepatic NAFLD microenvironment, only in the past decade have novel critical roles been unraveled for T cells in driving chronic inflammation toward HCC. The metabolic and immune microenvironment interact to recreate a tumor-promoting and immune-suppressive terrain, responsible for resistance to anticancer therapy. In this article, we will review the specific functions of several T-cell populations involved in NAFLD and NAFLD-driven HCC. We will illustrate the cellular crosstalk with other immune cells, regulatory networks or stimulatory effects of these interactions, and role of the metabolic microenvironment in influencing immune cell functionality. Finally, we will present the pros and cons of the current therapeutic strategies against NAFLD-related HCC and delineate possible novel approaches for the future.

Application of droplet digital polymerase chain reaction of plasma methylated septin 9 on detection and early monitoring of colorectal cancer.

Methylated septin 9 (SEPT9) has been approved for non-invasive screening of colorectal cancer (CRC), but data on monitoring of CRC is sparse. Droplet digital polymerase chain reaction (ddPCR), with higher detection precision and simpler quantification than conventional PCR, has not been applied in SEPT9 detection. We explored the role of SEPT9 ddPCR for CRC detection and to measure serial SEPT9 levels in blood samples of CRC patients before and 3-month after surgery. SEPT9 methylated ratio, methylated abundance, and CEA levels were all higher in CRC patients than normal controls (all P < 0.05). The area under the curve (AUC) for methylated ratio and abundance to detect CRC was 0.707 and 0.710, respectively. There was an increasing trend for SEPT9 methylated abundance from proximal to distal cancers (P = 0.017). At 3-month after surgery, both methylated abundance and ratio decreased (P = 0.005 and 0.053, respectively), especially methylated abundance in stage III and distal cancer (both P < 0.01). We have developed a ddPCR platform for the quantitative detection of plasma SEPT9 in CRC patients. SEPT9 methylated abundance had an early post-operative decline, which may be useful in monitoring of treatment response.

Metabolism-Associated Epigenetic and Immunoepigenetic Reprogramming in Liver Cancer.

Metabolic reprogramming and epigenetic changes have been characterized as hallmarks of liver cancer. Independently of etiology, oncogenic pathways as well as the availability of different energetic substrates critically influence cellular metabolism, and the resulting perturbations often cause aberrant epigenetic alterations, not only in cancer cells but also in the hepatic tumor microenvironment. Metabolic intermediates serve as crucial substrates for various epigenetic modulations, from post-translational modification of histones to DNA methylation. In turn, epigenetic changes can alter the expression of metabolic genes supporting on the one hand, the increased energetic demand of cancer cells and, on the other hand, influence the activity of tumor-associated immune cell populations. In this review, we will illustrate the most recent findings about metabolic reprogramming in liver cancer. We will focus on the metabolic changes characterizing the tumor microenvironment and on how these alterations impact on epigenetic mechanisms involved in the malignant progression. Furthermore, we will report our current knowledge about the influence of cancer-specific metabolites on epigenetic reprogramming of immune cells and we will highlight how this favors a tumor-permissive immune environment. Finally, we will review the current strategies to target metabolic and epigenetic pathways and their therapeutic potential in liver cancer, alone or in combinatorial approaches.

XCR1+ type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are prevalent liver conditions that underlie the development of life-threatening cirrhosis, liver failure and liver cancer. Chronic necro-inflammation is a critical factor in development of NASH, yet the cellular and molecular mechanisms of immune dysregulation in this disease are poorly understood. Here, using single-cell transcriptomic analysis, we comprehensively profiled the immune composition of the mouse liver during NASH. We identified a significant pathology-associated increase in hepatic conventional dendritic cells (cDCs) and further defined their source as NASH-induced boost in cycling of cDC progenitors in the bone marrow. Analysis of blood and liver from patients on the NAFLD/NASH spectrum showed that type 1 cDCs (cDC1) were more abundant and activated in disease. Sequencing of physically interacting cDC-T cell pairs from liver-draining lymph nodes revealed that cDCs in NASH promote inflammatory T cell reprogramming, previously associated with NASH worsening. Finally, depletion of cDC1 in XCR1DTA mice or using anti-XCL1-blocking antibody attenuated liver pathology in NASH mouse models. Overall, our study provides a comprehensive characterization of cDC biology in NASH and identifies XCR1+ cDC1 as an important driver of liver pathology.

Development of salient medication reminders to facilitate information transfer during transition from inpatient to primary care: the Delphi process.

OBJECTIVE: Transitional care is important to successful hospital discharge. Providing patients with a clear and concise summary of medication-related information can help improve outcomes, in particular, among older adults. The present study aimed to propose a framework for the development of salient medication reminders (SMR), which include drug-related risks and precautions, using the Delphi process. DESIGN: Identification of potential SMR statements for 80% of medication types used by older adult patients discharged from geriatric medicine departments, followed by a Delphi survey and expert panel discussion. SETTINGS: Medical and geriatric departments of public hospitals in Hong Kong. PARTICIPANTS: A panel of 13 geriatric medical experts. OUTCOME MEASURE: A Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree) points, scoring item relevance, importance and clarity. The minimum of 70% consensus was required for each statement to be included. RESULTS: The expert panel achieved consensus through the Delphi process on 80 statements for 44 medication entities. Subsequently, the SMR steering group endorsed the inclusion of these statements in the SMR to be disseminated among older adults at the time of discharge from geriatric medicine departments. CONCLUSIONS: The Delphi process contributed to the development of SMR for older adult patients discharged from public hospitals in Hong Kong. Patient experience with and staff response to the SMR were assessed at four hospitals before implementation at all public hospitals.

The Counterintuitive Relationship between Telomerase Activity and Childhood Emotional Abuse: Culture and Complexity.

BACKGROUND: A burgeoning literature has found relationships between telomere length, telomerase activity, and human health and longevity. Although some research links a history of childhood adversity with shortened telomere length, our review found no prior research on the relationship between child maltreatment history and telomerase activity in adulthood. We hypothesized a negative relationship between child maltreatment and telomerase activity and hypothesized that the association would be moderated by sex. METHODS: These relationships were tested on a sample of 262 Hong Kong Chinese adults (200 females versus 62 males) with mild to moderate depression. RESULTS: Counterintuitively, emotional abuse was positively associated with telomerase activity, while other maltreatment types were non-significant. The positive relationship between emotional abuse and telomerase activity was significantly moderated by the sex of the participant. CONCLUSIONS: We advance two possible explanations for this finding (1) a culturally informed resilience explanation and (2) a homeostatic complexity explanation. The two explanations are not mutually exclusive. This trial is registered under Hong Kong Clinical Trial Register number HKCTR-1929. SIGNIFICANCE STATEMENT: Emotional abuse was significantly positively associated with telomerase activity. There are at least two non-mutually exclusive explanations for the findings. Simply put, either (1) in the cultural context of Hong Kong emotional abuse was not a risk factor, and/or (2) the conceptualization of telomerase activity as a straightforward indicator of longevity is overly simplistic. The first story we might term a "resilience explanation" while the second we might call a "homeostatic complexity" story.

Trust as a mediator in the relationship between childhood sexual abuse and IL-6 level in adulthood.

Childhood sexual abuse (CSA) has been shown to predict the coupling of depression and inflammation in adulthood. Trust within intimate relationships, a core element in marital relations, has been shown to predict positive physical and mental health outcomes, but the mediating role of trust in partners in the association between CSA and inflammation in adulthood requires further study. The present study aimed to examine the impact of CSA on inflammatory biomarkers (IL-6 and IL-1ß) in adults with depression and the mediating role of trust. A cross-sectional survey data set of adults presenting with mood and sleep disturbance was used in the analysis. CSA demonstrated a significant negative correlation with IL-6 level (r = -0.28, p<0. 01) in adults with clinically significant depression, while trust showed a significant positive correlation with IL-6 level (r = 0.36, p < .01). Sobel test and bootstrapping revealed a significant mediating role for trust between CSA and IL-6 level. CSA and trust in partners were revealed to have significant associations with IL-6 level in adulthood. Counterintuitively, the directions of association were not those expected. Trust played a mediating role between CSA and adulthood levels of IL-6. Plausible explanations for these counterintuitive findings are discussed.

Combined Use of Common Fecal and Blood Markers for Detection of Endoscopically Active Inflammatory Bowel Disease.

INTRODUCTION: Monitoring of disease activity is essential in patients with inflammatory bowel disease. Although endoscopic remission is the ideal therapeutic goal, noninvasive biomarkers (blood and fecal) are more acceptable to patients and are less costly. We evaluated the performance of combinations of fecal and blood markers on the detection of endoscopically active disease. METHODS: Patients with ulcerative colitis (UC) or Crohn's disease (CD) on stable medications were recruited. Blood markers included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), albumin, platelet count (PLT), and hemoglobin. Fecal biomarkers included fecal calprotectin (FCT) and fecal immunochemical test (FIT). These markers were compared with the endoscopic Mayo score for UC and the Simple Endoscopic Score for CD. RESULTS: One hundred thirteen patients (mean age 44.7 years, 63.7% men, 54.9% patients with UC and 45.1% patients with CD) were recruited. FCT correlated well with FIT (r = 0.58), CRP (r = 0.56), ESR (r = 0.40), albumin (r = -0.54), PLT (r = 0.61), and hemoglobin (r = -0.35; all Ps < 0.001). Among 66 patients with endoscopic evaluation, 39.4% with endoscopically active disease had higher FCT, FIT, CRP, ESR, PLT, lower albumin, and hemoglobin compared with those in endoscopic remission (all Ps < 0.01). All 7 markers demonstrated good area under receiver operating characteristics (>0.7), with FCT being the best (0.91) for endoscopically active disease. Combining FCT and FIT improved the specificity to 95%, but the sensitivity decreased to 65.4%. In the subgroup analysis of UC, adding PLT to FIT improved the sensitivity and specificity to 100% and 90.9%, respectively. DISCUSSION: The combined use of fecal biomarkers and blood indexes is superior to the use of fecal biomarkers alone in identifying endoscopically active disease.

Impact of Locally Adopted Simulation-Based Crew Resource Management Training on Patient Safety Culture: Comparison Between Operating Room Personnel and General Health Care Populations Pre and Post Course.

Crew resource management (CRM) was introduced to enhance patient safety and reduce medical errors through multidisciplinary learning experience. This study investigates the impact of locally adopted simulation-based CRM training on participants' perceptions and knowledge. A 32-item web-based questionnaire was administered pre course, 1 month, and 1 year post course to assess changes in perceptions and knowledge. Another 12-item paper-based questionnaire was administered immediately post course to assess reactions. Among 712 participants analyzed, 165 were operating room staff. The majority agreed that the training is useful and relevant in daily practice. All participants showed significant improvements in perception and knowledge 1 month post course; however, these improvements declined 1 year post course. The CRM course is associated with satisfactory reaction (Kirkpatrick level 1) and improvement in attitude and knowledge (level 2) toward patient safety. However, the effect may be short-lived and regular refresher courses should be mandatory to sustain momentum of ongoing change.

Methylated Septin 9 and Carcinoembryonic Antigen for Serological Diagnosis and Monitoring of Patients with Colorectal Cancer After Surgery.

With the increasing incidence and mortality of colorectal cancer (CRC), early and accurate diagnosis is of paramount priority to combat this cancer. Epigenetic alterations such as DNA methylation are innovative biomarkers for CRC, due to their stability, frequency, and accessibility in bodily fluids. In this study, blood samples were prospectively collected from patients before and after operation for CRC for determination of methylated septin 9 (mSEPT9) and compared to carcinoembryonic antigen (CEA). The sensitivity of using mSEPT9 methylation status for diagnosing CRC was significantly higher than using elevated CEA levels (73.2% vs 48.2%; p value < 0.001). The sensitivities of both tests increased with higher tumor staging (P = 0.004 and 0.04 respectively). Combined mSEPT9 and CEA had higher accuracy than single CEA or mSEPT9 (P = 0.009 and 0.532 separately). An increase in the methylation level of mSEPT9 detected in the post-operative samples was associated with a higher mortality rate (15.2% vs 1.8%; P = 0.024) and the presence of metastasis (27.3% vs 7.0%; P = 0.013). mSEPT9 was more sensitive than CEA for diagnosing CRC, and combined mSEPT9 and CEA was more accurate. After curative resection, detection of increased mSEPT9 methylation level may indicate adverse outcomes.

Outcomes of community-based and home-based pulmonary rehabilitation for pneumoconiosis patients: a retrospective study.

BACKGROUND: Pneumoconiosis patients receive community-based or home-based pulmonary rehabilitation (PR) for symptom management and enhancement of physical and mental well-being. This study aimed to review the clinical benefits of community-based rehabilitation programmes (CBRP) and home-based rehabilitation programmes (HBRP) for PR of pneumoconiosis patients. METHODS: Archival data of pneumoconiosis patients who participated in CBRP and HBRP between 2008 and 2011 was analysed. There were 155 and 26 patients in the CBRP and HBRP respectively. The outcome measures used in the pre- and post-tests were Knowledge, Health Survey Short Form-12 (SF-12), Hospital Anxiety and Depression Scale (HADS), 6-Min Walk Test (6MWT), and Chronic Respiratory Questionnaire (CRQ). Paired t-tests and the Analysis of Covariance (ANCOVA) using the patients' baseline lung functions as the covariates were performed to examine the changes in the outcomes after completing the programmes. Hierarchical multiple regression analyses were used to examine the relationships between patient's programme participation factors and different scores of the outcome measures. RESULTS: After controlling for patients' baseline lung capacities, significant improvements were revealed among patients participated in CBRP in the scores of the 6MWT, Knowledge, HADS, SF-12 PCS, and CRQ emotion and mastery. The different scores in the Knowledge and HADS were correlated with the patients' levels of programme participation. In contrast, significant improvements were only found in the scores of the Knowledge and 6MWT among patients who participated in HBRP. The gain scores of the 6MWT were correlated with the patients' levels of programme participation. CONCLUSIONS: Both CBRP and HBRP benefited patients' levels of exercise tolerance and knowledge about the disease. CBRP provided greater benefits to patients' mental and psychosocial needs. In contrast, HBRP was found to improve patients' physical function, but did not have significant impacts on patients' mental health and health-related quality of life. The attendance of patients and the participation of their relatives in treatment sessions were important factors in enhancing the positive effects of CBRP and HBRP. These positive outcomes confirm the value of pulmonary rehabilitation programmes for community-dwelling pneumoconiosis patients.

Managing serious clinical deterioration in a tertiary hospital in Hong Kong: from indicators development to multiple measures in reducing the rates.

RATIONALE, AIMS AND OBJECTIVES: Timely detection and management of acutely deteriorating patients can save lives. Tuen Mun Hospital (TMH), a 1800-bed acute tertiary hospital serving more than 1.06 million populations in Hong Kong, is exploring to quantitatively monitor serious clinical deterioration (SCD) and uses it to guide patient care improvement initiatives. METHODS: Literature review on definition and measurement of SCD was conducted. Monthly SCD rates of TMH were first calculated according to the published methodology and benchmarked against those of international centres. A refined composite clinical indicator good for local use was compiled. In the second phase, p-control charts of SCD have been plotted based on cumulative data. RESULTS: TMH's performance was comparable with that of international centres. SCD on p-control charts has been plotting since January 2013. There were peaks in all 4 SCD rates during the winter surge period in 2013-2014. In the third phase, multiple measures have been taking to reduce the SCD rates including targeting the 3 main factors of winter surge situation. We are delighted to observe that the pattern did not repeat in the rate of cardiac arrest without do not attempt cardiopulmonary resuscitation (DNACPR) and rate of death without DNACPR in the same period in 2014-2015. CONCLUSIONS: SCD becomes a clinical governance tool to monitor the performance of clinical teams in treating acutely deteriorating patients in TMH. Any abnormal patterns or indications of special cause variations in the control charts would alert leaders to look for root causes of special cause variations and manage accordingly. We hope that this project will extend to corporate level and become a sustainable clinical indicator to guide audits, quality improvement initiatives and strategic planning.

DNA protective effect of ginseng and the antagonistic effect of Chinese turnip: A supplementation study.

AIM: The aim of this clinical study is to provide scientific evidence for supporting traditional Chinese application and usage to the patients. For this purpose, we tested the ability if Panax ginseng extract to lower oxidative damage to nuclear DNA in human lymphocytes by comparing the effect of cooked Chinese turnip on this effect. MATERIALS AND METHODS: Seven healthy subjects (4 males and 3 females from 37 to 60 years) participated two occasions which were at least 2 weeks apart. About 2 mL of fasting blood sample for baseline measurement was taken on arrival. They were requested to ingest the content of 5 ginseng capsules in 200 mL water. The subject remained fasting for 2 h until the second blood sample taken. In the other occasion, the experiment was repeated except a piece of cooked turnip (10 g) was taken with the ginseng extract. The two occasions could be interchanged. Comet assay was performed on two specimens on the same day for the evaluation of lymphocytic DNA damage with or without oxidative stress. RESULTS: For the group with ginseng supplementation, there was a significant decrease in comet score for hydrogen peroxide (H2O2) treatment over the 2-h period while no change in DNA damage for unstressed sample. For the group with ginseng together with turnip supplementation, there was no significant difference in comet score for both H2O2 treatment and phosphate-buffered saline treatment. Ginseng extract could reduce DNA damage mediated by H2O2 effectively, but this protection effect was antagonized by the ingestion of cooked turnip at the same time. CONCLUSION: In the current study, commercial ginseng extract was used for supplementing volunteers. Ginseng extract could protect DNA from oxidative stress in vivo while turnip diminished the protection.

Impact of Death Work on Self: Existential and Emotional Challenges and Coping of Palliative Care Professionals.

Palliative care professionals, such as social workers, often work with death and bereavement. They need to cope with the challenges on "self" in working with death, such as coping with their own emotions and existential queries. In this study, the authors explore the impact of death work on the self of palliative care professionals and how they perceive and cope with the challenges of self in death work by conducting a qualitative study. Participants were recruited from the palliative care units of hospitals in Hong Kong. In-depth interviews were conducted with 22 palliative care professionals: five physicians, 11 nurses, and six social workers. Interviews were transcribed to text for analysis. Emotional challenges (for example, aroused emotional distress from work) and existential challenges (for example, shattered basic assumptions on life and death) were identified as key themes. Similarly, emotional coping (for example, accepting and managing personal emotions) and existential coping (for example, rebuilding and actualizing life-and-death assumptions) strategies were identified. This study enhances the understanding of how palliative care professionals perceive and cope with the challenges of death work on the self. Findings may provide insights into how training can be conducted to enhance professionals' self-competence in facing these challenges.

Cyclooxygenase-1 serves a vital hepato-protective function in chemically induced acute liver injury.

Cyclooxygenase-1 (COX-1) is the constitutive form of the COX enzyme family, which produces bioactive lipids called prostanoids. Although the role of COX-2 in liver diseases has been studied, little is known about the function of COX-1 in liver injury. We aimed to investigate the role and mechanism of COX-1 in acute liver injury. Carbon tetrachloride (CCl(4)) was administered to induce acute liver injury in wild-type or COX-1-deficient mice. Both genetic (partially or completely) deletion of COX-1 expression and pharmacological inhibition of COX-1 activity in mice exacerbated acute liver injury induced by CCl(4), revealing the (1) histopathological changes and increased serum levels of aminotransferases; (2) oxidative stress in the liver partly through the action of cytochrome P450 2E1-dependent pathway; (3) enhanced inflammatory and chemoattractive responses with increased number of activated macrophages; and (4) increased apoptosis through both intrinsic and extrinsic apoptotic pathways. These pathological changes were partly through the modulation of transcription factor-dependent pathways (eg, NF-κB and C/EBP-α). Pre-treatment with prostaglandin E2 (PGE(2)) or 5-lipoxygenase (5-LO) inhibitor in homozygous COX-1 knockout mice significantly ameliorated CCl(4)-induced hepatic injury. In addition, level of hepato-protective molecules (eg, OSM and OSMR) and associated liver regeneration pathway were significantly inhibited by the deficiency of COX-1 but restored by the addition of PGE(2) or the inhibition of 5-LO. Furthermore, the alternative arachidonic acid metabolism pathway of 5-LO, which induced additional inflammation in the liver, was activated in response to the deficiency of COX-1. In conclusion, basal expression of COX-1 is essential for the protection of liver against chemical-induced hepatotoxicity and required for hepatic homeostatic maintenance.