BACKGROUND:Ammonia poisoning is considered to be the main hypothesis for the pathogenesis of hepatic encephalopathy.Ammonia can lead to psychiatric and cognitive behavioral disorders,although the specific pathological molecular mechanisms remain unclear.OBJECTIVE:To investigate the effects of ammonia poisoning on cognitive behavior and hippocampal neuronal synapses in mice.METHODS:Thirty-two C57BL/6J mice were randomly divided into a normal control group and an ammonium chloride group,with 16 mice in each group.Normal saline was injected intraperitoneally in the control group,and ammonium chloride(10 mmol/kg)was injected intraperitoneally in the ammonium chloride group to construct a model of ammonia poisoning,once a day.After 7 days of ammonium chloride intervention,blood samples were collected from the hearts of six mice in each group for blood ammonia concentration detection.Behavioral experiments,including the open field test,novel object recognition test,and Y-maze test,were performed to assess mental and cognitive-behavioral changes in mice.Finally,hippocampal tissues were extracted for western blot analysis to detect the expression levels of synaptophysin and postsynaptic density protein-95 in hippocampal neurons.RESULTS AND CONCLUSION:The blood ammonia concentration was significantly elevated in the ammonium chloride group compared with the control group(P＜0.05).Mice in the ammonium chloride group showed anxiety-like behavior and disinhibition phenomenon,and a significant decrease in recognition memory and working memory ability.Western blot results revealed that the expression of synaptophysin and postsynaptic density protein-95 protein in hippocampal neurons in the ammonium chloride group was lower than that in the control group(P＜0.05).To conclude,ammonia poisoning can induce hippocampal neuronal synaptic damage,leading to psychiatric and cognitive behavioral abnormalities in mice.

BACKGROUND:Ammonia poisoning is considered to be the main hypothesis for the pathogenesis of hepatic encephalopathy.Ammonia can lead to psychiatric and cognitive behavioral disorders,although the specific pathological molecular mechanisms remain unclear.OBJECTIVE:To investigate the effects of ammonia poisoning on cognitive behavior and hippocampal neuronal synapses in mice.METHODS:Thirty-two C57BL/6J mice were randomly divided into a normal control group and an ammonium chloride group,with 16 mice in each group.Normal saline was injected intraperitoneally in the control group,and ammonium chloride(10 mmol/kg)was injected intraperitoneally in the ammonium chloride group to construct a model of ammonia poisoning,once a day.After 7 days of ammonium chloride intervention,blood samples were collected from the hearts of six mice in each group for blood ammonia concentration detection.Behavioral experiments,including the open field test,novel object recognition test,and Y-maze test,were performed to assess mental and cognitive-behavioral changes in mice.Finally,hippocampal tissues were extracted for western blot analysis to detect the expression levels of synaptophysin and postsynaptic density protein-95 in hippocampal neurons.RESULTS AND CONCLUSION:The blood ammonia concentration was significantly elevated in the ammonium chloride group compared with the control group(P＜0.05).Mice in the ammonium chloride group showed anxiety-like behavior and disinhibition phenomenon,and a significant decrease in recognition memory and working memory ability.Western blot results revealed that the expression of synaptophysin and postsynaptic density protein-95 protein in hippocampal neurons in the ammonium chloride group was lower than that in the control group(P＜0.05).To conclude,ammonia poisoning can induce hippocampal neuronal synaptic damage,leading to psychiatric and cognitive behavioral abnormalities in mice.

Purpose: The optimal sequencing of targeted therapies and the role of primary tumor resection (PTR) in KRAS wild-type metastatic colorectal cancer (mCRC) remain unclear. This study compared survival outcomes in patients treated with first-line cetuximab plus FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) versus bevacizumab plus FOLFIRI, followed by second-line oxaliplatin-based chemotherapy and later-line trifluridine/tipiracil or regorafenib. Methods: This retrospective cohort study used Taiwan’s National Health Insurance Research Database and the Taiwan Cancer Registry. Patients diagnosed with mCRC between 2013 and 2019 were included if they received first-line cetuximab or bevacizumab plus FOLFIRI, followed by later-line trifluridine/tipiracil or regorafenib. Patients were stratified by PTR status. Primary endpoints were overall survival and survival during trifluridine/tipiracil or regorafenib treatment. Secondary endpoints included time to treatment discontinuation (TTD) and TTD during trifluridine/tipiracil or regorafenib therapy. Stabilized inverse probability of treatment weighting was used for adjustment. Results: Among 559 patients, 278 were assigned to the non-PTR group and 281 to the PTR group. In the non-PTR group, the cetuximab cohort demonstrated significantly longer survival during trifluridine/tipiracil or regorafenib therapy (6.2 months vs. 4.9 months; hazard ratio [HR], 0.72) and longer TTD1 (the interval between initiation of first-line therapy and the start of second-line chemotherapy; 11.8 months vs. 9.5 months; HR, 0.67) than the bevacizumab cohort. Survival differences between regimens were less pronounced among patients who underwent PTR. Conclusion First-line cetuximab plus FOLFIRI may confer a survival advantage over bevacizumab in patients with KRAS wild-type mCRC without PTR, including during later-line therapy with trifluridine/tipiracil or regorafenib, whereas bevacizumab appears to provide more consistent benefits in those with PTR.

Background: The World Health Organization published the 2019 Integrated Care for Older People (ICOPE) framework to guide, assess, and promote the intrinsic capacity (IC) of older adults, referring to their physical and mental health. This study aims to investigate the relationship between IC and frailty among older adults. Methods: This cross-sectional study was conducted in a medical center in Taiwan in 2021. Two hundred ten patients over 65 admitted to the geriatric ward were invited to participate. The questionnaire included an IC measure, Fried Frailty Scale, and demographic items. The IC measure was ascertained using the six domains of ICOPE (cognition, mobility, nutrition, visual, hearing, and depressive symptoms). The Fried Frailty Scale was used to categorize participants as robust (Fried Frailty Scale=0), prefrail (Fried Frailty Scale=1-2), or frail (Fried Frailty Scale ≥3). Multinomial logistic regression was used to analyze the association between individual ICOPE domains and frailty stages, while adjusting for confounders. Results: Among the participants, 39.0% were prefrail, and 28.6% were frail. Limited mobility and depressive symptoms were significantly associated with prefrail (adjusted odds ratio [aOR]=4.44, 95% confidence interval [CI] 1.82–10.82; aOR=8.41, 95% CI 1.75–40.37) and frail (aOR=11.57, 95% CI 3.63–36.93; aOR=13.77, 95% CI 2.62–72.49) individuals, respectively. Malnutrition (aOR=4.01, 95% CI 1.18–13.62) and hearing loss (aOR=4.37, 95% CI 1.09–19.66) were significantly associated with frail older adults. Conclusion Limited mobility and depressive symptoms occurring at the prefrail stage could be used as assessment items for early detection of prefrail.

To report two cases of psychiatric symptoms associated with zonisamide, an antiepileptic drug, and raise clinical awareness of this potential adverse effect. Two male patients with epilepsy treated with zonisamide were retrospectively analyzed. Case 1 (25 years old) developed acute emotional and behavioral abnormalities (e.g., insomnia, aggression, incoherent speech) after switching from sodium valproate to zonisamide (200 mg/day). Case 2 (48 years old) had long-term zonisamide use (≥5 years) with persistent treatment-resistant psychotic symptoms (e.g., delusions, command hallucinations). Clinical courses, medication adjustments, and symptom responses were documented. In Case 1, psychiatric symptoms resolved after discontinuing zonisamide and switching to sodium valproate, with improved mood stability and reduced impulsivity. In Case 2, despite escalating antipsychotic medications (risperidone, clozapine), psychotic symptoms persisted, likely due to ongoing zonisamide use. Both cases highlighted zonisamide’s potential to exacerbate or induce psychiatric manifestations, possibly via mechanisms involving sodium/calcium channel inhibition and neurotransmitter dysregulation (e.g., dopamine, serotonin). Zonisamide can cause or worsen psychiatric symptoms, particularly in vulnerable individuals. Clinicians should monitor for mental health changes during zonisamide treatment and consider drug discontinuation or substitution with alternative antiepileptics (e.g., sodium valproate) if psychiatric adverse effects emerge. Awareness of this association is crucial to avoid misdiagnosis and optimize epilepsy management.

ObjectiveTo evaluate the quality of clinical practice guidelines and expert consensus statements on knee osteoarthritis （KOA） based on the Appraisal of Guidelines for Research & Evaluation Ⅱ （AGREE Ⅱ）， thus providing a new perspective for clinical selection as well as guideline development and updating. MethodsA systematic search was conducted for KOA-related guidelines and consensus statements published from November 1， 2019 to December 31， 2025. The databases and platforms searched included CNKI， VIP， Wanfang Data， PubMed， Web of Science， the National Institute for Health and Care Excellence （NICE）， SinoMed， Yimaitong， and relevant official websites. Two researchers independently screened the literature， and four researchers used AGREE Ⅱ to score the included documents and completed the quality appraisal after reaching a unified understanding. Subgroup analyses were further performed according to developing organization， document type， medical approach， funding status， and region of development， and longitudinal comparisons were conducted by year of publication. ResultsA total of 23 guidelines and consensus statements were included. The standardized scores of the six AGREE Ⅱ domains， from the highest to the lowest， were clarity of presentation ［（70.36±8.13）%］， scope and purpose ［（67.46 ± 11.44）%］， editorial independence ［（64.50±20.01）%］， rigor of development ［（62.24±15.26）%］， stakeholder involvement ［（55.73±10.29）%］， and applicability ［（53.89±13.17）%］. In terms of overall recommendation， 6 documents were rated as grade A and 17 as grade B. Stratified analyses showed that professional organizations scored higher than comprehensive organizations. The overall scores of traditional Chinese medicine/integrative medicine and Western medicine guidelines （or consensus statements） were similar. Guidelines scored higher than consensus statements. The overall scores were similar between documents with reported funding and those without reported funding. International guidelines scored higher than domestic guidelines. Longitudinal comparisons showed that the largest number of documents was published in 2021. The overall scores were higher in 2021—2022， and some domain scores declined in 2023—2024. Overall， the quality of recent guidelines and consensus statements for KOA showed slight fluctuations， without a clear linear trend. ConclusionThe included guidelines and consensus statements for KOA can generally serve as references for clinical practice. However， the quality across domains remains uneven， and stakeholder involvement and applicability are still weak domains. Future guideline development and updating should further improve methodological standardization and transparency in reporting.

Objective To establish an animal model of osteoporosis combined with liver cirrhosis and conduct preliminary investigation into the effect of liver cirrhosis on bone loss in mice and the underlying mechanisms.Methods The experimental animals were 25 6-week-old female C57BL/6 mice with a body weight of approximately 20-22 g.A comorbidity model of liver cirrhosis and osteoporosis was established in the mice by ovariectomy combined with carbon tetrachloride(CCl4)induction.The mice were randomly assigned to 4 groups(n=5 in each group),including a control group,a liver cirrhosis group,an osteoporosis group,and a cirrhosis and osteoporosis comorbidity group.Pathological changes in the liver were observed via HE staining,Sirius Red staining,and serum liver function indicators.Bone mass and morphological changes were assessed using micro-CT and HE staining.ELISA,Western blot,and immunohistochemistry were performed to assess the expression of insulin-like growth factor-1(IGF-1)in serum and liver tissues.An additional IGF-1 intervention group was established to investigate the potential role of IGF-1 in the comorbidity of liver cirrhosis and osteoporosis,and changes in bone mass and morphology were analyzed via micro-CT and HE staining.Results Compared with the control and osteoporosis groups,the liver cirrhosis and cirrhosis-osteoporosis comorbidity groups exhibited significant inflammatory cell infiltration and collagen fiber deposition in liver tissues,along with markedly increased serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBIL)(P＜0.05).According to the Micro-CT and HE staining results,the cirrhosis-osteoporosis comorbidity group showed reduced bone mass and decreased trabecular numbers in the distal femur compared to those in the osteoporosis group,with the differences being statistically significant(P＜0.05).ELISA,Western blot,and immunohistochemistry demonstrated significantly reduced expression of IGF-1 in the liver and serum of the cirrhosis-osteoporosis comorbidity group(P＜0.05).Notably,exogenous IGF-1 treatment restored bone mass in mice with liver cirrhosis combined with osteoporosis(P＜0.05).Conclusion Through ovariectomy combined with CCl4 induction,a mouse model of liver cirrhosis combined with osteoporosis was successfully established.IGF-1 may serve as a potential molecular mechanism and therapeutic target mediating the liver cirrhosis-osteoporosis comorbidity.

Objective To explore the correlation between glycolysis related indexes of peripheral blood mononuclear cells(PBMCs)[glucose transporter 1(GLUT1),fructose-2,6-diphosphatase 3(PFKFB3)and lactate kinase M2(PKM2)]and intracranial pressure and clinical prognosis of patients with hypertensive cerebral hemorrhage(HICH)who broke into the ventricle.Methods 85 HICH patients hospitalized in our hospital from January 2021 to June 2022 were retrospectively collected as the research participants.The levels of PKM2,GLUT1 and PFKFB3 in PBMCs were analyzed by enzyme-linked immunosorbent assay kit.Six months after the onset of HICH,the short-term outcome was evaluated by modified Rankin scale(mRS),and the patients were divided into good prognosis(mRS score≤2)and poor prognosis(mRS score≥3).Results The levels of PKM2,PFKFB3 and GLUT1 in PBMCs of HICH patients with ventricular rupture were further lower than those of the patients without ventricular rupture(P<0.05).Six months after discharge,8 patients(22.9%)with HICH in non-ventricular rupture group had poor prognosis,while 28 patients(56.0%)with HICH in ventricular rupture group had poor prognosis,and the difference was statistically significant(χ2=9.263,P=0.002).Compared with the group with good prognosis,the levels of PKM2 and GLUT1 in PBMCs of HICH patients with poor prognosis were lower(P<0.05).Compared with the good prognosis group,the levels of PKM2 and GLUT1 in PBMCs of HICH patients with poor prognosis group were lower in HICH patients with ventricular rupture(P<0.05).In HICH patients who broke into the ventricle,the AUC of PKM2 and GLUT1 in predicting the poor prognosis of HICH patients were 0.879(95%CI:0.807～0.951)and 0.897(95%CI:0.831～0.963),respectively.Conclusion The levels of PKM2 and GLUT1 in PBMCs of patients with HICH breaking into ventricles decrease significantly,and are negatively correlated with intracranial pressure,which can be used to predict the short-term prognosis of the patients.

INTRODUCTION: We aimed to understand the awareness and attitudes of elderly Southeast Asians towards telehealth services during the coronavirus disease 2019 (COVID-19) pandemic in this study. METHODS: In this qualitative study, 78 individuals from Singapore (51.3% female, mean age 73.0 ± 7.6 years) were interviewed via telephone between 13 May 2020 and 9 June 2020 during Singapore's first COVID-19 'circuit breaker'. Participants were asked to describe their understanding of telehealth, their experience of and willingness to utilise these services, and the barriers and facilitators underlying their decision. Transcripts were analysed using thematic analysis, guided by the United Theory of Acceptance Use of Technology framework. RESULTS: Of the 78 participants, 24 (30.8%) were able to describe the range of telehealth services available and 15 (19.2%) had previously utilised these services. Conversely, 14 (17.9%) participants thought that telehealth comprised solely home medication delivery and 50 (51.3%) participants did not know about telehealth. Despite the advantages offered by telehealth services, participants preferred in-person consultations due to a perceived lack of human interaction and accuracy of diagnoses, poor digital literacy and a lack of access to telehealth-capable devices. CONCLUSION Our results showed poor overall awareness of the range of telehealth services available among elderly Asian individuals, with many harbouring erroneous views regarding their use. These data suggest that public health education campaigns are needed to improve awareness of and correct negative perceptions towards telehealth services in elderly Asians.
Humans ; COVID-19/epidemiology* ; Female ; Telemedicine ; Aged ; Male ; Singapore/epidemiology* ; Qualitative Research ; Health Knowledge, Attitudes, Practice ; SARS-CoV-2 ; Aged, 80 and over ; Middle Aged ; Pandemics ; Awareness ; Asian People ; Southeast Asian People

INTRODUCTION: The rising rate of adolescent suicide, and the burden of self-harm and mental health disorders, pose significant threats to Singapore's future health outcomes and human potential. This study sought to examine the risk profile and healthcare utilisation patterns of Singaporean adolescents who presented to the emergency department (ED) for suicidal or self-harm behaviour. METHOD: A retrospective review of medical records for patients aged 10 to 19 years who visited Singapore's KK Women's and Children's Hospital ED for suicidal or self-harm attempts from January to December 2021 was conducted. RESULTS: A total of 221 patients were identified, with a predominance of female patients (85.5%) over males (14.5%). The mean age was 14.2 ± 1.4 years. Intentional drug overdose (52.0%) was the most commonly used method. Significantly more females presented for intentional paracetamol overdose (46.6% versus [vs] 28.1%, P=0.049), whereas jumping from a height was more common among males (18.8% vs 5.8%, P=0.022). The most frequently observed mental health challenges were stress-related and emotional coping difficulties (50.7%), followed by mood and anxiety symptoms (53.4%). A history of self-harm and suicidal behaviours were the most common psychosocial risk factors. Within the year prior to their ED presentation, 15.4% had accessed healthcare services for mild medical ailments, 19.5% for medically unexplained symptoms, and 17.2% for previous self-harm or suicide attempts. CONCLUSION Most cases involved psychosocial and emotional regulation difficulties, some of which displayed sex-specific patterns, rather than complex psychiatric disorders. The identified predictive factors can help inform Singapore's National Mental Health and Well-being Strategy, to guide targeted and transdiagnostic interventions in schools and community settings.
Humans ; Adolescent ; Singapore/epidemiology* ; Female ; Male ; Suicide, Attempted/psychology* ; Emergency Service, Hospital/statistics & numerical data* ; Self-Injurious Behavior/psychology* ; Retrospective Studies ; Child ; Young Adult ; Drug Overdose/epidemiology* ; Risk Factors ; Acetaminophen/poisoning* ; Patient Acceptance of Health Care/statistics & numerical data* ; Sex Factors