ObjectiveTo establish a new noninvasive， simple， and convenient clinical predictive model by identifying independent predictive factors for rebleeding after endoscopic therapy in cirrhotic patients with esophagogastric variceal bleeding （EGVB）， and to provide a basis for individualized risk assessment and development of clinical intervention strategies. MethodsCirrhotic patients with EGVB who were diagnosed and treated in The First Affiliated Hospital of Xi’an Medical University from September 2018 to October 2023 were enrolled as subjects， and according to whether the patient experienced rebleeding within 1 year after endoscopic therapy， they were divided into rebleeding group with 93 patients and non-rebleeding group with 84 patients. Clinical data were collected and analyzed. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. A Logistic model was established based on the results of the univariate and multivariate analyses， and the receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to assess the accuracy of the model. R software was used to visualize the model by plotting a nomogram， and the Bootstrap method was used for internal validation of the model. ResultsThe multivariate analysis showed that red blood cell count （RBC）， cholinesterase （ChE）， alkaline phosphatase （ALP）， albumin （Alb）， thrombin time （TT）， portal vein trunk diameter， sequential therapy， and primary prevention were independent predictive factors for rebleeding. Based on the results of the multivariate analysis， a logistic model was established as logit（P）=-0.805-1.978×（RBC）+0.001×（ChE）-0.020×（ALP）-0.314×（Alb）+0.567×（TT）+0.428×（portal vein trunk diameter）-2.303×［sequential therapy （yes=1， no=0）］-2.368×［primary prevention （yes=1， no=0）］. The logistic model （AUC=0.928， 95% confidence interval ［CI］： 0.893—0.964， P<0.001） had a better performance in predicting rebleeding than MELD score （AUC=0.603， 95%CI： 0.520—0.687， P=0.003）， Child-Pugh class （AUC=0.650， 95%CI： 0.578—0.722， P=0.001）， and FIB-4 index （AUC=0.587， 95%CI： 0.503—0.671， P=0.045）. The model had an optimal cut-off value of 0.607， a sensitivity of 0.817， and a specificity of 0.817. Internal validation confirmed that the model had good predictive performance and accuracy. ConclusionSequential therapy， implementation of primary prevention， an increase in RBC， and an increase in Alb are protective factors against rebleeding， while prolonged TT and widened main portal vein diameter are risk factors. The logistic model based on these independent predictive factors can predict rebleeding and thus holds promise for clinical application.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

ObjectiveSpinal cord injury (SCI) directly impairs the regulatory function of the autonomic nervous system, induces intestinal dysfunction, and significantly reduces patients’ quality of life. Preclinical studies have shown that electroacupuncture (EA) therapy can regulate the brain-gut axis and is used to treat central nervous system diseases such as major depressive disorder, Alzheimer’s disease and Parkinson’s disease. Recent research has established that fecal microbiota transplantation (FMT) from EA-treated SCI rats restored intestinal motility and colonic morphology. However, it remains unclear whether the regulation of gut microbiota by EA therapy directly contributes to neural repair after SCI. This study aims to explore whether gut microbiota mediates the neuroprotective effect of EA in the treatment of SCI and its possible mechanism. MethodsThe study employed RNA transcriptome analysis of spinal cord tissue to characterize gene expression profiles and to identify key signaling pathways following EA treatment for SCI. Hematoxylin-Eosin (HE) staining and Nissl staining were used to observe the morphological changes in spinal cord tissue. Western blot (WB) and enzyme-linked immunosorbent assay (ELISA) were applied to detect the effects of EA on the expression of proteins related to nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) -dependent pyroptosis. Using 16S rDNA sequencing, the study observed alterations in gut microbiota diversity and community composition in SCI rats. Prior to establishing SCI models, rats were pretreated with an antibiotic cocktail to induce gut dysbiosis, and the effects on intestinal function and spinal cord neural repair were evaluated. FMT was performed to investigate the regulatory effects of post-EA FMT on motor function, general status, liver and spleen indices, and NLRP3-mediated pyroptosis in SCI rats. ResultsEA improved motor function and reduced regulated neuronal cell death in SCI rats. Transcriptomic analysis demonstrated the activation of immune- and inflammation-related pathways post-SCI, including NOD-like receptors, nuclear factor-kappa B(NF-κB), and Toll-like receptor (TLR) pathways. EA primarily influenced intestinal inflammation and autoimmune functions. 16S rDNA sequencing illustrated that EA did not alter the diversity of gut microbiota. However, EA altered the gut microbiota composition in SCI rats, increasing Lactobacillus and Akkermansia genera while rebalancing the Firmicutes/Bacteroidetes ratio. Furthermore, depletion of gut microbiota by antibiotics disrupted the intestinal barrier, reduced the expression of intestinal barrier proteins Zonula Occludens-1 (ZO-1) and Occludin, elevated serum lipopolysaccharide-binding protein (LBP) levels, exacerbated spinal cord tissue damage, and hindered motor function recovery in SCI rats. FMT from donors treated with EA reduced LBP levels in the intestine, blood, and spinal cord of rats, inhibited the TLR4 myeloid differentiation primary response protein 88 (MyD88)-NF‑κB pathway and NLRP3-dependent pyroptosis, and improved motor function. On the other hand, FMT treatment resulted in decreased body weight and food intake, whereas FMT using EA-treated donors effectively alleviated these alterations. ConclusionEA effectively alleviated neuroinflammatory responses in rats with SCI, primarily through regulating the gut microbiota and suppressing the NLRP3-dependent pyroptosis signaling pathway.

Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that severely affects the health of the elderly, marked by its incurability, high prevalence, and extended latency period. The current approach to AD prevention and treatment emphasizes early detection and intervention, particularly during the pre-AD stage of mild cognitive impairment (MCI), which provides an optimal “window of opportunity” for intervention. Clinical detection methods for MCI, such as cerebrospinal fluid monitoring, genetic testing, and imaging diagnostics, are invasive and costly, limiting their broad clinical application. Speech, as a vital cognitive output, offers a new perspective and tool for computer-assisted analysis and screening of cognitive decline. This is because elderly individuals with cognitive decline exhibit distinct characteristics in semantic and audio information, such as reduced lexical richness, decreased speech coherence and conciseness, and declines in speech rate, voice rhythm, and hesitation rates. The objective presence of these semantic and audio characteristics lays the groundwork for computer-based screening of cognitive decline. Speech information is primarily sourced from databases or collected through tasks involving spontaneous speech, semantic fluency, and reading, followed by analysis using computer models. Spontaneous language tasks include dialogues/interviews, event descriptions, narrative recall, and picture descriptions. Semantic fluency tasks assess controlled retrieval of vocabulary items, requiring participants to extract information at the word level during lexical search. Reading tasks involve participants reading a passage aloud. Summarizing past research, the speech characteristics of the elderly can be divided into two major categories: semantic information and audio information. Semantic information focuses on the meaning of speech across different tasks, highlighting differences in vocabulary and text content in cognitive impairment. Overall, discourse pragmatic disorders in AD can be studied along three dimensions: cohesion, coherence, and conciseness. Cohesion mainly examines the use of vocabulary by participants, with a reduction in the use of nouns, pronouns, verbs, and adjectives in AD patients. Coherence assesses the ability of participants to maintain topics, with a decrease in the number of subordinate clauses in AD patients. Conciseness evaluates the information density of participants, with AD patients producing shorter texts with less information compared to normal elderly individuals. Audio information focuses on acoustic features that are difficult for the human ear to detect. There is a significant degradation in temporal parameters in the later stages of cognitive impairment; AD patients require more time to read the same paragraph, have longer vocalization times, and produce more pauses or silent parts in their spontaneous speech signals compared to normal individuals. Researchers have extracted audio and speech features, developing independent systems for each set of features, achieving an accuracy rate of 82% for both, which increases to 86% when both types of features are combined, demonstrating the advantage of integrating audio and speech information. Currently, deep learning and machine learning are the main methods used for information analysis. The overall diagnostic accuracy rate for AD exceeds 80%, and the diagnostic accuracy rate for MCI also exceeds 80%, indicating significant potential. Deep learning techniques require substantial data support, necessitating future expansion of database scale and continuous algorithm upgrades to transition from laboratory research to practical product implementation.

One of the leading therapies for acute lymphoblastic leukemia (ALL) is the chemotherapeutic agent PEGylated E. coli-derived-l-asparaginase (PEG-ASNase). Due to the high risk of dose-limiting liver injury, characterized by clinically elevated levels of hepatic transaminases, PEG-ASNase therapy is generally avoided in adult patients. Our preclinical investigations have indicated that PEG-ASNase-induced liver injury is associated with the release of free fatty acids (FFAs) from white adipose tissue (WAT), suggesting potential lipotoxic effects. However, it remains uncertain whether PEG-ASNase directly induces hepatotoxicity or sensitizes hepatocytes to FFA-induced toxicity. Our results show that PEG-ASNase treatment results in hepatocyte apoptosis and lipid peroxidation. Ex vivo and in vitro studies in mouse and human WAT suggest that PEG-ASNase induces the expression of adipose triglyceride lipase (ATGL), activates the lipase, and stimulates adipose tissue lipolysis, suggesting that the FFAs from WAT may contribute to the observed liver injury. Moreover, treatment with PEG-ASNase sensitizes hepatocytes to FFA-induced lipotoxicity. Mechanistically, our RNA-sequencing (RNA-seq) analyses reveal that PEG-ASNase-induced sensitization to lipotoxicity is accompanied by the induction of Cyp2e1. We demonstrated that this sensitization effect is attenuated by both pharmacological and genetic inhibition of Cyp2e1. Our findings suggest that PEG-ASNase therapy induces WAT lipolysis and sensitizes hepatocytes to hepatic lipotoxicity in a Cyp2e1-dependent manner.

Methods: Thirty patients with PDVO of the lumbar or thoracic spine treated with transforaminal interbody debridement and fusion (TIDF) with AIBG between March 2014 and May 2022 were reviewed (AIBG group). For comparative analysis, 28 PDVO patients who underwent TIDF without AIBG between January 2009 and June 2011 were enrolled (non-AIBG group). The minimum follow-up duration was 2 years. Clinical characteristics and surgical indications were comparable in the two groups. C-reactive protein (CRP) levels and the postoperative antibiotics course were compared between the two groups. Results: Surgical treatment for PDVO resulted in clinical improvement and adequate infection control. Despite the shorter postoperative intravenous antibiotic duration (mean: 19.0 days vs. 39.8 days), the AIBG group had significantly lower CRP levels at postoperative 4 and 6 weeks. The mean Visual Analog Scale pain scores improved from 7.3 preoperatively to 2.2 at 6 weeks postoperatively. The average angle correction at the last follow-up was 7.9°. Conclusions TIDF with AIBG for PDVO can achieve local infection control with a faster reduction in CRP levels, leading to a shorter antibiotic duration.

Purpose: Plasmablastic lymphoma (PBL) is a rare, aggressive lymphoma that is characterized by terminal B-cell differ‑ entiation. In the West, PBL usually occurs in patients with immunodeficiencies, particularly those induced by human immunodeficiency virus (HIV) infection. We investigated the clinicopathological features of PBL at a single institute in Taiwan, where HIV infection is rare. Methods: This retrospective chart review identified PBL cases that were treated at a single institute in southern Tai‑ wan between 2008 and 2024. Results: We identified nine patients (four males and five females; median age 71 years). Of the eight patients tested for HIV, only one tested positive. Pathologically, the tumors showed plasmablastic morphology and immunopheno‑ type, and three (33%) cases tested positive for Epstein–Barr virus. Six (67%) patients presented with Stage IV disease, including five (56%) with malignant effusion. Six patients were treated with chemotherapy and the remaining three received only supportive care. During a median follow-up of 10 months, five patients died of progressive disease, two died of unrelated diseases, and two were alive with PBL relapse. Conclusion In Taiwan, PBL constitutes a rare and aggressive clinical condition and is frequently associated with malignant effusion. In contrast to Western patients, the PBL in most patients from Taiwan was unrelated to HIV infection.

INTRODUCTION: Adverse childhood experiences (ACEs) are associated with significant long-term impacts, yet few interventions specifically target ACE exposure, especially in Asian populations. Anchor, Singapore's first home visitation programme, addresses maltreat-ment among preschool children. This study evaluated Anchor's impact on children's developmental and behavioural outcomes. METHOD: We conducted a prospective evaluation of children under 4 years assessed for maltreatment from November 2019 to July 2023. Developmental and behavioural progress was measured every 6 months using the Ages and Stages Questionnaires (ASQ-3) and ASQ:Social-Emotional (ASQ:SE-2), and annually using the Child Behaviour Checklist (CBCL). RESULTS: The results of 125 children (mean age 20.0 months, 48% female) were analysed. The mean length of stay in programme was 21.2 (7.3) months. At baseline, 92 (73.6%) children were at risk of develop-mental delay and 25 (31.7%) children aged ≥18 months had behavioural concerns. The programme was associated with significant improvements in gross motor (P=0.002) and fine motor (P=0.001) domains of the ASQ-3 and internalising problem scale (P=0.001) of the CBCL. CONCLUSION Anchor effectively enhances develop-mental and behavioural outcomes for children exposed to maltreatment. Targeted early intervention through such programmes can mitigate adverse impacts, optimising developmental trajectories and potentially reducing the long-term clinical and economic burdens associated with ACEs.
Humans ; Female ; Male ; Child Abuse/therapy* ; Child, Preschool ; Singapore ; House Calls ; Infant ; Prospective Studies ; Child Development ; Developmental Disabilities/epidemiology* ; Program Evaluation ; Child Behavior Disorders ; Child Behavior

INTRODUCTION: Paediatric sexual assault (SA) victims should be assessed for post-exposure prophylaxis (PEP) to mitigate the risk of sexually transmitted infections (STIs). We describe the clinical characteristics of children and young persons (CYPs) presenting with SA at KK Women's and Children's Hospital in Singapore, viral PEP (human immunodeficiency virus [HIV] and hepatitis B virus [HBV]) prescribing practices, and STI evaluation at follow-up. METHOD: Medical records of CYPs ≤16 years who presented with SA between January 2022 and August 2023 were reviewed, including assault and assailant characteristics, baseline and follow-up STI screening, PEP prescription, adherence and follow-up attendance. CYPs with SA in the preceding 72 hours by HIV-positive or HIV-status unknown assailants with high-risk characteris-tics were eligible for HIV PEP. RESULTS: We analysed 278 CYPs who made 292 SA visits. There were 40 (13.7%) CYPs eligible for HIV PEP, of whom 29 (82.9%) received it. Among those tested at baseline, 9% and 34.9% of CYPs tested positive for Chlamydia trachomatis and Gardnerella vaginalis, respectively. None tested positive for Neisseria gonorrhoeae, Trichomonas vaginalis, HIV, HBV or hepatitis C. Majority of CYPs tested were HBV non-immune (n=167, 67.6%); only 77 (46.1%) received the vaccine. Out of 27 CYPs eligible for HBV PEP with immunoglobulin, only 21 (77.7%) received immunoglobulin. A total of 37 CYPs received HIV PEP, including 8 who were retrospectively deemed ineligible. Only 10 (27%) completed the course. Overall, 153 (57.7%) CYPs attended follow-up, and none seroconverted for HIV or HBV. CONCLUSION We report suboptimal rates of HBV post-exposure vaccination, and low compliance to HIV PEP and follow-up among paediatric SA victims. Factors contri-buting to poor compliance should be examined to optimise care for this vulnerable population.
Humans ; Post-Exposure Prophylaxis/methods* ; Female ; Child ; Adolescent ; Singapore/epidemiology* ; HIV Infections/prevention & control* ; Male ; Sexually Transmitted Diseases/epidemiology* ; Retrospective Studies ; Hepatitis B/prevention & control* ; Follow-Up Studies ; Child, Preschool ; Sex Offenses/statistics & numerical data* ; Child Abuse, Sexual