Compared with traditional therapies for chronic liver disease （CLD）， Bifidobacterium has the characteristics of multi-target intervention， high biosafety， and good host compatibility and provides new strategies for intervention of CLD progression in terms of microecological regulation. Various studies have shown that Bifidobacterium regulates liver homeostasis and exerts a therapeutic effect on CLD by regulating intestinal flora， maintaining antioxidation， promoting energy consumption， alleviating inflammation， improving glycolipid metabolism， and exerting an antitumor effect. This article systematically reviews the studies on Bifidobacterium in the treatment of CLD in China and globally， explores their different mechanisms， and elaborates on the interaction between related signaling pathways （such as the nuclear factor erythroid 2-related factor 2 signaling pathway and the adenosine monophosphate-activated protein kinase signaling pathway） and the liver， in order to provide a basis for probiotic intervention in liver pathology， as well as new ideas for the comprehensive treatment of CLD.

Objective: To understand the awareness of chikungunya fever knowledge and its related factors among medical college students in Baise City, so as to provide a scientific basis to offer relevant courses and special education. Methods: From July to August 2025, 7 286 enrolled medical students were selected by a sampling method from a medical college in Baise City to participate in the questionnaire survey. The questionnaire covered epidemiological characteristics, clinical symptoms, and prevention/control knowledge of chikungunya fever. Statistical analyses including the Chi quare test and multivariate Logistic regression models were performed. Results: The overall awareness rate of chikungunya fever knowledge among the medical students was 18.89%. Among the knowledge items, the awareness rate of "the high incidence season" was the highest (84.05%), while that of "the infectious period" was the lowest (17.80%). Multivariate Logistic regression analysis showed that medical students with female (a OR= 1.37 , 95%CI =1.20- 1.57 ), the age for over 25 years old (a OR=1.76, 95%CI =1.05-2.93), whose father had a middle school educational level (a OR=1.18, 95%CI =1.05-1.31), and majored in preventive medicine (a OR=1.54, 95%CI =1.10-1.67) had relatively higher awareness rates of chikungunya fever knowledge (all P <0.05). In contrast, students of Zhuang ethnicity (a OR= 0.87 , 95%CI =0.76-0.98) and majoring in nursing (a OR=0.74, 95%CI =0.61-0.91) or pharmacy (a OR=0.70, 95%CI =0.52-0.95) had relatively lower awareness rates (all P <0.05). Conclusions The awareness rate of chikungunya fever related knowledge among medical college students in Baise City is relatively low. Schools should take targeted publicity measures to improve medical students awareness.

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: Adrenocortical hormones, particularly 11-oxygenated androgens, are pivotal in female reproductive health and fertility. Standardized detection kits and population-specific reference intervals are lacking in China, hindering related clinical applications. Methods: A HPLC-tandem mass spectrometry (HPLC-MS/MS) pipeline was developed, rigorously validated, and applied to simultaneously quantify corticosterone, cortisone, cortisol, 18-OH cortisol, androstenedione (A4), 11β-hydroxyandrostenedione (11-OH A4), dehydroepiandrosterone, and dehydroepiandrosterone sulfate in serum samples from 455 reproductive-aged women (18–45 yrs) in Guangxi, China. Age-dependent concentration trends were analyzed, and reference intervals stratified by age (2.5th to 97.5th percentiles) were established. Correlations with body-composition metrics, ethnicity, and the menstrual cycle were investigated. Results: The HPLC-MS/MS method demonstrated high precision (intra- and inter-assay CVs < 15%), accuracy, and sensitivity. All eight hormones exhibited significant age-related declines (P < 0.001 for seven hormones; P = 0.001 for 11-OH A4). Notably, 11-OH A4 levels were significantly lower in the 35–45-yr (3.05 nmol/L) and 25–34-yr (3.09 nmol/L) age groups than in the 18–24-yr (3.57 nmol/L) age group, whereas no significant difference was observed between the 35–45-yr and 25–34-yr age groups. Weak negative correlations were observed between the body mass index and corticosterone and cortisone levels, whereas ethnicity and the menstrual cycle showed no significant associations with hormone levels. Conclusions We developed an HPLC-MS/MS-based method for simultaneously quantifying eight adrenocortical hormones, including 11-OH A4, and defined age-specific reference intervals for reproductive-aged Chinese women. These findings advance the clinical utility of adrenocortical hormones in diagnosing and managing reproductive disorders.

Objectives: . Idiopathic sudden sensorineural hearing loss (ISSNHL) is a significant cause of hearing loss. Intratympanic steroid injection (ITSI) is commonly used as an initial or salvage treatment; however, the lack of a standardized treatment protocol has resulted in variability in clinical practice. In addition, no efficient prediction model currently exists to support personalized management. Therefore, this study aimed to develop tailored management strategies for ISSNHL using a machine-learning model. Methods: . This retrospective multicenter cohort study was conducted between January 2015 and December 2020, with data analysis performed between January 2021 and March 2024. Patients were selected based on the International Classification of Diseases, 10th Revision criteria for ISSNHL, along with relevant medication and procedure codes. Patients with pure-tone audiogram results not meeting ISSNHL criteria, better initial hearing in the affected ear, an identifiable etiology, no post-treatment audiogram, or delayed treatment (>6 weeks) were excluded. We included 770 patients diagnosed with ISSNHL who received ITSI. The primary outcome was the area under the receiver operating characteristic curve for prediction performance. Recovery status was determined using the last pure-tone audiogram. Modeling was conducted on the Quanta for Medical Care AI platform using five machine-learning algorithms and a nested cross-validation framework, in which feature selection and hyperparameter tuning were performed in the inner folds and model performance was evaluated in the outer folds. Results: . A random forest classifier outperformed the other models in predicting hearing outcomes, achieving an area under the receiver operating characteristic curve of 0.788. Time to ITSI was the most influential treatment-related factor, with ITSI administered within 10 days of hearing loss being associated with better outcomes. This model can be used to provide personalized prognostic estimates under different treatment protocols. Conclusion . The machine-learning-based prediction model facilitates personalized treatment strategies and timely treatment adjustments for ISSNHL, thereby optimizing the likelihood of complete recovery.

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 explore the risk factors and alterations in functional connectivity of brain networks in end-stage renal disease （ESRD） patients complicated by frailty. MethodsA total of 84 patients with ESRD were enrolled and divided into the frailty group （31 cases） and non-frailty group （53 cases） according to the Chinese version of the Tilburg Frailty Indicator （TFI）. Cranial magnetic resonance imaging （MRI） data， neuropsychological test results and clinical data were collected for all subjects. Logistic regression analysis was used to explore risk factors for frailty in ESRD patients， and image preprocessing and independent component analysis were performed to compare differences in brain network functional connectivity between the two groups. ResultsLogistic regression analysis showed that high blood urea nitrogen level， depression， malnutrition， and sleep disturbance were risk factors for frailty in patients with ESRD （P<0.05）， while a higher level of education served as a protective factor （P<0.05）. Compared with the non-frailty group， the frailty group exhibited significantly weakened functional connectivity between the sensorimotor network and the visual network （P<0.05）. ConclusionHigh levels of blood urea nitrogen， depression， malnutrition， and sleep disorders can increase the risk of frailty in patients with end-stage renal disease （ESRD）， while a higher educational level may reduce this risk. Patients with ESRD complicated by frailty exhibit a significant decrease in functional connectivity between the sensorimotor network （SMN） and visual network （VN）， which provides novel imaging evidence for exploring the central neural mechanisms underlying the development of frailty in ESRD patients.

Objective To investigate the role and potential mechanism of glutathione peroxidase 3 (GPX3) in ischemia-reperfusion injury (IRI) during kidney transplantation. Methods C57BL/6 mice were divided into four groups according to different interventions: sham operation group (Sham group), kidney transplantation group (KT group), kidney transplantation + GPX3 overexpression group (KT+GPX3 group) and kidney transplantation + GPX3 overexpression + reactive oxygen species (ROS) agonist group (KT+GPX3+CADD522 group). Twenty-four hours after model establishment, inferior vena cava blood was collected to detect blood urea nitrogen (BUN) and serum creatinine (Scr). Left renal tissues were harvested for immunofluorescence staining to detect ROS and NADPH oxidase 2 (NOX2). Enzyme-linked immunosorbent assay (ELISA) was performed to measure neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), tumor necrosis factor (TNF) -α and interleukin (IL)-1β. Western blotting was used to detect myeloperoxidase (MPO) and citrullinated histone H3 (CitH3). Results Compared with the Sham group, the expression level of GPX3 was decreased in the KT group; compared with the KT group, GPX3 expression was increased in the KT+GPX3 group; compared with the KT+GPX3 group, GPX3 expression was reduced in the KT+GPX3+CADD522 group (all P<0.05). Compared with the Sham group, the levels of Scr, BUN, NGAL and KIM-1 were elevated in the KT group; compared with the KT group, the above indicators were decreased in the KT+GPX3 group; compared with the KT+GPX3 group, the levels of Scr, BUN, NGAL and KIM-1 were increased in the KT+GPX3+CADD522 group (all P<0.05). Compared with the Sham group, the expression levels of NOX2 and ROS were increased in the KT group; compared with the KT group, NOX2 and ROS levels were decreased in the KT+GPX3 group; compared with the KT+GPX3 group, NOX2 and ROS levels were upregulated in the KT+GPX3+CADD522 group (all P<0.05). Compared with the Sham group, the expression levels of MPO and CitH3 were increased in the KT group; compared with the KT group, MPO and CitH3 levels were decreased in the KT+GPX3 group; compared with the KT+GPX3 group, MPO and CitH3 levels were increased in the KT+GPX3+CADD522 group (all P<0.05). Compared with the Sham group, the expression levels of TNF-α and IL-1β were increased in the KT group; compared with the KT group, TNF-α and IL-1β levels were decreased in the KT+GPX3 group; compared with the KT+GPX3 group, TNF-α and IL-1β levels were increased in the KT+GPX3+CADD522 group (all P<0.05). Conclusions GPX3 may alleviate renal tissue inflammation by inhibiting ROS-mediated neutrophil extracellular trap (NET) formation, thereby attenuating IRI in renal transplantation.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.
Atrial Fibrillation/physiopathology* ; Humans ; Acupuncture Therapy ; Vagus Nerve/physiology* ; Animals

Endothelial dysfunction is one of the early triggers of vascular remodeling during pulmonary hypertension (PH) with complex predisposing mechanisms, mainly via an unbalanced generation of vasoactive factors, increased expression of growth factors, prothrombotic elements, and inflammatory markers. Conventional treatment regimens are restricted to a single therapeutic pathway, which usually leads to limited clinical outcomes. Combination therapies targeting multiple cells and several signaling pathways are increasingly adopted in PH treatment. Herein, inspired by the cocrystal pleomorphism theory, we prepared rod-shaped nanococrystals of the endothelin-1 (ET-1) receptor antagonist (bosentan, BST) and the anti-inflammatory drug (andrographolide, AG) for targeting the pulmonary endothelium and alleviating PH. The 525 nm-sized co-delivery system displayed a rod-like morphology, preferentially accumulated in the pulmonary endothelium and alleviated pulmonary artery (PA) remodeling. A three-week treatment with the preparation significantly alleviated the monocrotaline (MCT)- or Sugen 5416/hypoxia (SuHx)-induced PH by reducing the pulmonary artery pressure, increasing the survival rate, improving the hemodynamics, and inhibiting vascular remodeling. Mechanistically, the nanococrystals collaboratively repaired endothelial dysfunction by suppressing the pathways of ET-1/NF-κB/ICAM-1/TNF-α/IL-6. In conclusion, the cocrystal-based strategy offers a promising approach for constructing co-delivery systems. The developed rod-shaped nanococrystals effectively target the pulmonary endothelium and relieve experimental PH.