Alcoholic liver disease (ALD) remains a significant clinical challenge with limited therapeutics. It is strongly associated with sarcopenia, which further worsens the prognosis in liver cirrhosis. Zinc-deficiency is a hallmark of ALD, impairing the liver's antioxidant defenses and alcohol metabolism. Here we identify a chaperone role for MG53/TRIM72 in facilitating crosstalk between zinc and alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH2), acting as a metabolic regulator of muscle-liver communication. In ALD, muscle-derived MG53 is transported to liver and mitigates liver damage. MG53 deficiency exacerbates hepatic zinc-deficiency and impairs ADH and ALDH2 activity, which are reversed by systemic administration of recombinant human MG53 (rhMG53). MG53's B-box motif coordinates zinc interaction with ADH and ALDH2, enhancing their enzymatic activity to clear toxic alcohol byproducts. We developed a bio-derived nanoparticle for co-delivery of rhMG53 and zinc, offering a promising therapeutic approach for ALD. In vivo findings are applicable to the male sex only.

Objective To evaluate the diagnostic performance of combining sonographic features with BRAFV600E mutation for differentiating benign and malignant Bethesda category u2162 thyroid nodules. Methods This retrospective cohort study included 275 patients (278 nodules) diagnosed as Bethesda category u2162 by ultrasound-guided fine needle aspiration cytology (US-FNAC) at First Affiliated Hospital of Army Medical University between January 2020 and December 2024, with final confirmation via surgical pathology or repeated US-FNAC. Nodules were classified as benign or malignant based on pathological results. Diagnostic efficacy of age, sex, 9 sonographic features, ACR TI -RADS score, US-FNAC nuclear morphology, and BRAFV600E mutation was analyzed using multivariate logistic regression. Results Significant differences existed in age, nodule margin, aspect ratio, maximum diameter, echogenicity, Adler blood flow grading, ACR TI-RADS classification, US-FNAC nuclear morphology, and BRAFV600E status between benign and malignant nodules (all Pu0026lt;0.05). Independent risk factors for malignancy included ageu226452 years (OR=7.444), BRAFV600E mutation (OR =108.218), ground-glass nuclei (OR =5.389), and abnormal cervical lymph nodes (OR=13.351, Pu0026lt;0.05). The combined model demonstrated accuracy was 0.823, sensitivity was 0.863, specificity was 0.925, positive predictive value was 0.977, negative predictive value was 0.649, and AUC was 0.955. Conclusion Integration of sonographic features and BRAFV600E mutation provides high diagnostic performance for Bethesda category u2162 thyroid nodules.

Objective: Non-diagnostic thyroid nodules (Bethesda I) account for 5%-20% of all thyroid nodules. Accurate differentiation of benign and malignant nodules can reduce unnecessary surgeries and repeat biopsies. Herein we evaluated the diagnostic efficacy of multigene testing in non-diagnostic thyroid nodules and developed a predictive model integrating molecular and clinical data. Methods: In this prospective cohort study, 1,175 patients with thyroid nodules were evaluated for inclusion, of which 218 patients with Bethesda I nodules met our inclusion criteria. The primary outcome was diagnostic accuracy of molecular testing, and the secondary outcome was the performance of a predictive model integrating molecular and clinical data. Results: Final histopathology identified 165 benign and 53 malignant nodules. Molecular testing detected 10 distinct point mutations and seven gene fusions. Among benign nodules, 147 tested negative and 18 tested positive, whereas 44 malignant nodules tested positive and nine tested negative. In nodules with ultrasound grades 4-5 and fine-needle aspiration cytology (FNAC) results categorized as non-diagnostic, molecular testing achieved sensitivity of 83.00%, specificity of 89.00%, positive predictive value (PPV) of 71.00%, negative predictive value (NPV) of 94.20%, and overall accuracy of 87.60%. The predictive model incorporated 18 clinical and 19 molecular features. Eleven non-zero predictors were selected via least absolute shrinkage and selection operator (LASSO), and the model achieved area under curve (AUC) of 0.95 in the training set and 0.96 in the testing set. Decision curve analysis indicated greater net benefit compared with conventional diagnostic approaches. Conclusions: Molecular testing significantly improved diagnostic accuracy for Bethesda I thyroid nodules. Integrating molecular and clinical data enabled the development of a robust predictive model, facilitating precise, individualized patient management and reducing the need for repeat FNAC and unnecessary surgeries.

Background:Sustaining self-management is critical for optimizing clinical outcomes in individuals with type 2 diabetes mellitus (T2DM). Although digital health interventions (DHIs) have shown benefits for glycemic control and self-care, much of this evidence has focused on efficacy, and the behavioral mechanisms through which DHIs produce sustained effects remain insufficiently understood. Clarifying these mechanisms could inform the development of theory-driven interventions. Objective:This study examined the longitudinal behavioral pathways through which Artificial Intelligence-based Health Education Accurately Linking System, a WeChat (Tencent)-based digital health program, influences T2DM self-management, using the Extended Multi-Theory Model (MTM) of health behavior change. Methods:An explanatory sequential mixed methods prospective longitudinal cohort study was conducted among adults with T2DM (aged ≥18 y and proficient in WeChat use), recruited from 45 primary health care institutions in Beijing, China, between July 2023 and July 2024. Self-management behavior was assessed as the primary outcome using the Summary of Diabetes Self-Care Activities, and psychosocial determinants using the Extended MTM Scale and the Diabetes-related Skills Scale. Exploratory and confirmatory factor analyses assessed the construct validity of the Extended MTM Scale. Structural equation modeling examined longitudinal pathways among Artificial Intelligence-based Health Education Accurately Linking System users across baseline and 3, 6, and 12 months. For the qualitative phase, a purposive subsample was selected through maximum variation sampling based on baseline glycated hemoglobin; interviews were analyzed thematically until thematic saturation, and integrated with quantitative findings using a joint display. Results:Of the 406 enrolled participants, 391 completed baseline assessments. The Extended MTM Scale demonstrated a 6-factor, 22-item structure with excellent internal consistency (Cronbach α=0.928) and satisfactory construct validity. The structural equation modeling showed satisfactory fit (CFI=0.984, RMSEA=0.036). Changes in the social environment (β=0.23, 95% CI 0.07-0.38; P=.003) and physical environment (β=0.25, 95% CI 0.10-0.40; P=.001) at baseline, and diabetes-related skills at month 6 (β=0.16, 95% CI 0.03-0.29; P=.01), were directly associated with self-management behavior at month 12, whereas behavioral confidence and emotional transformation showed no significant direct effects. Social environment changes were indirectly associated with behavioral confidence through participatory dialogue at month 3 (β=0.20, 95% CI 0.04-0.36; P=.01; β=0.66, 95% CI 0.57-0.74; P<.001). Thematic analysis of 17 interviews identified 3 domains: environmental context, cognitive processes, and attitudes and skills. Environmental factors converged across both data strands, while qualitative data expanded on the cognitive and attitudinal processes underlying sustained self-management. Conclusions:This study is among the first to apply the Extended MTM framework to DHI-supported T2DM self-management, with environmental factors emerging as key drivers alongside selected cognitive, attitudinal, and skills-related processes. Complementing efficacy-focused research, it illuminates the psychosocial pathways underlying sustained self-management and refines the Extended MTM in digital health contexts. These insights can inform the design of theory-driven DHIs in primary care.

To investigate the biological functions of TOP2A in HCC using bioinformatics and single-cell RNA sequencing (scRNA-seq) methods, and to explore the functional consequences of TOP2A in HepG2 and Huh-7 cells with TOP2A knockdown. This study aims to provide new theoretical insights and potential therapeutic targets for the early diagnosis and targeted treatment of HCC. Through the analysis of single-cell RNA sequencing data, the immunological significance of TOP2A and its relationship with the diagnosis and prognosis of HCC were studied. The expression levels of TOP2A in HCC and normal liver epithelial cells were validated using quantitative PCR (QPCR). siRNA technology was employed to interfere with TOP2A expression in HepG2 and Huh7 cells, and a TOP2A knockdown cell line was established. The transfection efficiency of siRNA was measured using QPCR and Western Blotting. The impact of TOP2A knockdown on the proliferation of HCC cells was assessed using the CCK8 assay. The effect of TOP2A on the migration ability of HCC cells was observed through a wound-healing assay. The influence of TOP2A knockdown on the invasive ability of HCC cells was examined using the Transwell assay. The effect of TOP2A knockdown on the apoptosis of HCC cells was evaluated using flow cytometry. This study integrated single-cell RNA sequencing and functional analyses identified TOP2A as a critical oncogenic driver in HCC. TOP2A expression was significantly upregulated in HCC tissues and strongly correlated with poor patient prognosis (P < 0.05). In vitro experiments showed that the efficiency of TOP2A knockdown mediated by siRNA was over 70% (P < 0.05), and it significantly inhibited the proliferation, invasion and migration of HCC cells (P < 0.05), promoted cell apoptosis (P < 0.05). Mechanistically, scRNA-seq revealed that TOP2A may promotes Tmem-to-Tex differentiation through the SPP1-CD44 axis. These findings position TOP2A as both a prognostic biomarker and a potential therapeutic target for overcoming immune evasion in HCC. TOP2A is significantly upregulated in HCC, and its expression level can serve as an independent prognostic biomarker. Knockdown of TOP2A can significantly inhibit the malignant phenotype of HepG2 and Huh7 cells. Moreover, the analysis shows that TOP2A may promote immune escape by modulating the SPP1-CD44 axis and remodeling the immune microenvironment. These findings not only reveal the crucial role of TOP2A in the progression of HCC, but also indicate that it may become a potential target for immunotherapy in HCC, providing a new theoretical basis for improving the precise treatment strategies for HCC patients.

Background: As the emerging of structural imbalance characterized by surging demand and insufficient high-quality supply in China’s health management system, smart health management services become a novel measure to address this gap. Smart health management services refer to the health monitoring, assessment and intervention with support of information communication and artificial intelligence technologies. Objective: To systematically analyze the current status, needs, and influencing factors of the using of smart health management services and devices among China’s adults, thereby providing evidence support and suggestions for its development. Methods: A mixed-methods design was employed, combining quantitative and qualitative research methods. In the quantitative section, participants aged 18 years and above were selected by a stratified cluster random sampling method, their intentions and behaviors in utilizing smart health management services were analyzed by structural equation model (SEM).In the qualitative research section, 13 interviewees were selected for semi-structured, one-on-one interviews, the findings were analyzed by grounded theory coding. Quantitative and qualitative findings were integrated using an explanatory sequential mixed-methods framework. Results: A total of 2786 adults participated the questionnaire survey with a response rate of 96.07 %. Of them, 13 participants agreed to attend the semi-structured, one-on-one interviews. The main findings are as follows: (1) 37.7 % of the adult participants used smart health management devices. The use rate presents decline with increasing age, and lower use among older adults. (2)The demand for smart health management systems shows a diversified trend, and significant differences between age groups. Overall, participants believe that certain basic functions of the smart health systems, such as health monitoring, are needed, and they hope that it can answer questions raised by users. Qualitative study further revealed that participants' needs for smart health systems are in line with Maslow's Hierarchy of Needs, which includes needs at various levels from ''basic life safety and health security'' to ''active learning and self-actualization.'' Young participants prefer the support function for basic preventive activities and optimization of lifestyle; older participants then are more concerned about whether the system has practical functions for disease management. (3)The average using willingness was moderately high (62.68 ± 20.65). In the SEM, behavioral attitude emerged as the strongest predictor of willingness of use(β=0.568, P < 0.001), followed by subjective norms (β = 0.103, P < 0.001) and media motivation (β = 0.094, P < 0.001). Electronic health literacy exerted significant indirect effects on both willingness (β = 0.045, P < 0.001) and behavior (β=0.051, P < 0.001) via media motivation, while perceived behavioral control influenced them indirectly (β = 0.014 and 0.016, both P < 0.001). Living in urban areas positively affected both willingness(β = 0.056, P < 0.001) and behavior (β = 0.125, P < 0.001). Health insurance coverage significantly promoted willingness (β = 0.039, P < 0.001). (4)Qualitative findings revealed multiple barriers to using, including high costs, product quality concerns, discomfort during using, and security issues. Attitudes toward smart health management devices were polarized, positive or negative evaluations stemmed directly from experience, perceived benefits, and device intelligence level, whereas neutral users tended to discontinue use due to a lack of perceived value. In addition, personal beliefs and cultural values strongly influenced individuals’ acceptance. Conclusion: The study identified a distinct pattern of “high wish and low use” among adults regarding smart health management services. Both using behavior and demand pattern exhibited clear age-specific differences and were shaped by a number of factors. To bridge the gap between willingness to use and actual using behavior, future efforts should focus on age-appropriate design, precision implementation, and collaboration with primary care facilities, thereby enhancing adults’ capacity for actively managing their health.

BACKGROUND:Perioperative stroke is a devastating surgical complication associated with high mortality rates. The goals of our study were to identify the predictors of postoperative stroke and to explore the possible role of intraoperative hypotension (IOH). METHODS:Medical records of patients undergoing non-cardiovascular, non-neurological surgery at Ningbo No.2 Hospital (January 1st, 2012-December 31st, 2023) were retrospectively analyzed. Logistic regression was used to screen for independent risk factors. The nomogram is used for the visualization of the model. RESULTS:This retrospective cohort study included 574,102 patients. Among 419,358 patients from 2012 to 2019, 848 (0.2 %) experienced postoperative stroke; cancer-related surgeries increased this incidence by 67 % (P < 0.001). In the cancer subgroup (multivariate analysis), significant predictors included age, history of stroke, atrial fibrillation, renal failure, elevated preoperative D-Dimer, and sustained IOH (>40 % decrease in mean arterial pressure [MAP] from baseline for >15 min) (all P < 0.05). Furthermore, the nomogram model developed based on the above variables demonstrated effective performance in predicting the occurrence of postoperative stroke in both the training set (January 1st, 2012-December 31st, 2019; n = 65,312) and the validation set (January 1st, 2020-December 31st, 2023; n = 28,326), with areas under the curve (AUCs) of 0.843 and 0.852, respectively. CONCLUSION:This study confirms that cancer-related surgeries significantly increase postoperative stroke risk and demonstrates IOH's independent association in this subgroup. A validated nomogram provides an effective tool for prediction.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC). This multicenter case-control study aimed to elucidate the clinicopathological features and prognosis of patients with resectable HAS. This retrospective study included 1387 GC patients treated at Ningbo No. 2 Hospital between January 2016 and December 2023, among whom 23 were HAS cases and incorporated 61 HAS patients from three external centers. Prognostic factors were analyzed using the Cox proportional hazards model. Propensity score matching (PSM) at a ratio of 4:1 and Kaplan-Meier survival curves were employed for analysis. The prevalence of HAS in this cohort was 1.1%. Among the 84 HAS patients with a median follow-up of 28 months, 47.6% had serum alpha-fetoprotein (AFP) levels exceeding 20 ng/mL. During the follow-up period, 44.0% of patients experienced relapses, predominantly through hepatic metastasis (62.2%). Univariate and multivariate analyses identified preoperative serum AFP levels between 200-500 ng/mL and TNM stages III/IV as independent prognostic factors for overall survival (OS). Elevated preoperative levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and TNM stages III/IV were independently associated with poorer disease-free survival (DFS). Conversely, open surgery and a Ki-67 proliferation index exceeding 50% were found to act as protective factors for both OS and DFS, with postoperative chemotherapy improving OS outcomes. After PSM adjustment, the analysis included 248 non-HAS patients and 62 HAS patients, revealing significantly better OS (P=0.043) and DFS (P=0.009) among non-HAS patients. Open radical surgery followed by adjuvant chemotherapy is recommended for the treatment of resectable HAS. Overall, patients with HAS exhibit a less favorable prognosis compared to those with non-HAS.

AIMS:To investigate the global, regional, and national burden and risk factors of type 2 diabetes mellitus (T2DM) among older adults aged ≥65 years from 1990 to 2021, with projections to 2040. MATERIALS AND METHODS:Using the Global Burden of Disease database, this study analysed global, regional, and national T2DM burden and risk factors across sex, age groups, and Socio-Demographic Index (SDI) levels. Annual percentage changes were calculated, and predictions used a Bayesian age-period-cohort model. RESULTS:Among older adults aged ≥65 years, the global age-standardized prevalence and mortality of T2DM rose by 1.9% and 0.32% per year, respectively, from 1990 to 2021. T2DM's proportion of total disability-adjusted life years (DALYs) and mortality from all diseases increased, as did its share of T2DM cases across all age groups. Mortality rose fastest in the 85-89 group (0.52% annually). High SDI regions exhibited the highest prevalence, whereas lower SDI correlated with higher mortality rates. Eastern Europe and Uzbekistan experienced the fastest DALYs growth. The global burden of T2DM in older adults is projected to continue increasing by 2040. Globally, high body mass index contributed most to T2DM burden, while high temperature and sugar-sweetened beverages (SSBs) showed the fastest-growing DALYs rates. The fastest-growing risk factor in high-SDI regions was sugar-sweetened beverages, while high temperature was the fastest-growing risk in low-SDI regions. CONCLUSIONS:Diabetes cases among older adults have tripled globally since 1990 and are projected to keep increasing. Wealthier nations face diet-related risks, while poorer regions are more affected by environmental factors. Region-specific prevention strategies are urgently needed.

OBJECTIVE:This study uses the technology acceptance model (TAM) as the theoretical framework to explore the predicting factors of intention to adopt wearable activity trackers and the actual wearing behavior among Chinese type 2 diabetes mellitus (T2DM) patients over 50 with different personality traits. METHODS:The wearable activity tracker (WAT) was freely distributed to T2DM patients recruited from 22 community health service stations affiliating to four community health service centers in Beijing. A questionnaire survey was conducted to examine predicting factors of adoption intention after a week's try-on. Actual wearing behavior for 30-day was obtained from the exclusive cloud. Latent profile analysis was used to explore personality portraits. Structural equation modeling (SEM) was used to analyze the data. RESULTS:A total of 668 patients (age over 50) with T2DM were included in the analysis. According to the latent profile analysis, the T2DM patients in this study could be classified into four personality profiles: Negative, Anxious, Introverted-Stable (IS), and Active-Responsible (AR). The results of SEM indicated that perceived ease of use (PEOU, β = 0.37, P < 0.01), perceived usefulness (PU, β = 0.31, P < 0.01), social image (SI,β = 0.11, P < 0.01), and privacy concerns (PC, β = -0.50, P < 0.01) directly influenced behavioral intention. Neuroticism positively influenced SI (β = 0.18, P < 0.01). Conscientiousness and openness positively impacted PEOU (β = 0.20, P < 0.01; β = 0.09, P < 0.05). Agreeableness negatively influenced PC (β = -0.17, P < 0.01). Openness and extraversion positively impacted individual innovation(β = 0.15, P < 0.01; β = 0.17, P < 0.01). CONCLUSIONS:Adoption intentions of WAT was the main factor influencing the actual wearing behavior of older patients with T2DM. PEOU, PU, and SI were the main facilitators of adoption intention, while PC was the main barrier. Different personality traits have their particular path of influence on WAT adoption intentions. It is recommended that future interventions with new devices or technologies for older patients with T2DM be carried out according to the preferences and needs of patients with different personality traits, such as product ease of use, innovativeness, and aesthetics, to promote patients' intention and actual use behaviors.

ImportanceGastric cancer, including gastroesophageal junction cancer, is one of the most commonly diagnosed cancers worldwide, with high mortality. Sugemalimab is a fully human anti–programmed death-ligand 1 (PD-L1) antibody. The combination of sugemalimab and chemotherapy showed promising antitumor activity and safety in a phase 1b study among patients with treatment-naive, unresectable, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma. This combination was further evaluated in the GEMSTONE-303 phase 3 trial.ObjectiveTo evaluate the efficacy of sugemalimab in combination with capecitabine and oxaliplatin (CAPOX) compared with placebo plus CAPOX as first-line treatment for patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma with PD-L1 combined positive score (CPS) of 5 or greater.Design, Setting, and ParticipantsGEMSTONE 303 is a phase 3, randomized, double-blind, placebo-controlled study conducted at 54 sites in China that enrolled patients from April 9, 2019, through December 29, 2021, with follow-up to July 9, 2023. A total of 479 eligible patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma with PD-L1 CPS of 5 or greater who did not receive any prior systemic therapy were randomized.InterventionPatients received sugemalimab (1200 mg intravenously) (n = 241) or placebo (n = 238) every 3 weeks for up to 24 months, plus CAPOX every 3 weeks for up to 6 cycles.Main outcomes and MeasuresPrimary outcomes were overall survival and investigator-assessed progression-free survival.ResultsBaseline characteristics were well balanced between the 2 groups. Most patients were male (71.4% in sugemalimab group, 74.8% in placebo group). Median follow-up was 25.1 months in the sugemalimab group and 26.3 months in the placebo group. The sugemalimab group demonstrated significant improvements in overall survival (median, 15.6 months [95% CI, 13.3-17.8] vs 12.6 months [95% CI, 10.6-14.1]; hazard ratio, 0.75 [95% CI, 0.61-0.92]; P = .006) and progression-free survival (median, 7.6 months [95% CI, 6.4-7.9] vs 6.1 months [95% CI, 5.1-6.4]; hazard ratio, 0.66 [95% CI, 0.54-0.81]; P < .001). Grade 3 or higher treatment-related adverse events occurred in 53.9% of patients in the sugemalimab group and 50.6% in the placebo group.Conclusions and RelevanceSugemalimab plus chemotherapy significantly prolonged overall survival and progression-free survival with a manageable safety profile in previously untreated patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.Trial RegistrationClinicalTrials.gov Identifier: NCT03802591

Acute intrahepatic lymphangiectasia (IHL) is a pathologic condition characterized by abnormal dilation of the intrahepatic lymphatic vessels and related lymphedema, often resulting from impaired lymphatic drainage. Iatrogenic/non-iatrogenic abdominal injury and hepatic malignant neoplasms are the most common etiology of IHL. It is relatively common following liver transplantation, typically due to surgical manipulation or transient obstruction. In most cases, it is self-limiting and asymptomatic, requiring no specific intervention. To date, there have been no reports of IHL causing severe complications graded Clavien-Dindo III or higher. We report a case of acute IHL following liver transplantation that induced biliary and portal vein stenosis in the graft liver. This 51-year-old male patient with hepatitis B virus-related hepatocellular carcinoma developed acute IHL in the early posttransplant period, presenting with elevated alanine aminotransferase and bilirubin, diagnosed through imaging findings and cyst fluid analysis. Interventions included cyst aspiration, endoscopic biliary stenting, and percutaneous portal vein stenting due to biliary obstruction and portal vein stenosis. Liver function normalized, leading to discharge on postoperative day 60. At 5-month follow-up, imaging confirmed restored vascular and biliary patency, with sustained normal function over 8 months.

BACKGROUND:Anti-epidermal growth factor receptor monoclonal antibodies like cetuximab and panitumumab have revolutionized colorectal cancer therapy, but their benefits are offset by limiting toxicities that require precise prevention strategies. METHODS:We interrogated the FDA Adverse Event Reporting System (2004 Q1-2025 Q2) to map agent-specific toxicity signatures across age, sex and reporter strata under a multi-algorithm disproportionality framework. Four convergent metrics were required to declare a signal; demographic modifiers (age and sex) and reporter lens (medical vs non-medical personnel) were integrated. RESULTS:20920 cetuximab and 10280 panitumumab reports with single primary suspect status were identified. Cetuximab generated an early, age-independent AE burst: 54.4 % of events arose within 30 days. Panitumumab showed a protracted profile with only 40.8 % of events in the first month yet 5.4 % reported after one year versus 2.7 % for cetuximab. Panitumumab carried a higher fatality rate and disproportionately intense cutaneous signals, whereas cetuximab dominated radiation-synergy domains such as radiation skin injury. Age stratification revealed ≥65-year panitumumab users faced a 1.5-fold higher hypomagnesaemia ROR than younger patients; women reported higher dermatitis acneiform ROR values on panitumumab compared with cetuximab. Non-medical reporters amplified cetuximab radiation mucositis ROR to 3374.22, whereas panitumumab skin-toxicity ROR climbed to 958.54. CONCLUSION:Cetuximab and panitumumab exhibit divergent, demography-modulated safety narratives. Cetuximab amplifies acute radio-toxicity whereas panitumumab elicits a quantitatively stronger, more persistent mucocutaneous and electrolyte injury that is magnified by female sex, advancing age, and non-medical reporters reporting. These population-specific pharmacovigilance signatures refine risk-benefit assessments and should inform individualized monitoring strategies in precision oncology.

Background: With the number of internet users booming, problematic internet use (PIU) has become a public health threat. This study aims to figure out the inter-relationships between PIU symptoms and personality traits with network-based analysis among young people and to discuss the gender difference in the above networks. Methods: Based on a national cross-sectional study in 2022, 4655 Chinese adolescents and young adults aged 14 to 25 were included. We adopted the 6-item Short-Form Problematic Internet Use Questionnaire (PIUQ-SF-6) and the 10-item version of the Big Five Inventory (BFI-10) to measure PIU and personality traits, respectively. Network analysis was used to identify influential nodes and edges and compare the network models between male and female participants. Results: The mean age of 4655 participants was 19.84, and 52.1 % (2424) of them were females. There are differences in age and gender between participants with and without PIU (P < 0.05). The network of personality and PIU showed that 22 out of the 28 edges were estimated to be nonzero, and "obsession-neuroticism" was the strongest positive edge between the two communities. Central symptoms (i.e., "obsession" and "control disorder") and bridge symptoms (i.e., "obsession" and "neuroticism") have been identified. Gender differences existed in network global strength: female = 3.71, male = 3.18 (p < 0.001). Limitations: The cross-sectional study needs more evidence to build causal inference. Conclusions: The results of PIU-personality networks may contribute to the personalized prevention and treatment of PIU. The gender difference in PIU-personality networks also requires more attention and discussion.

BACKGROUND:Identifying molecular subtypes of breast cancer (BC) is of great significance in selecting optimal treatment strategy. Different molecular subtypes of BC have various vascular distribution characteristics. Contrast-enhanced ultrasound (CEUS) can dynamically display the microcirculation of tumor. This study intends to explore the conventional ultrasound and CEUS characteristics of different molecular subtypes of BC.METHODS:During this prospective study, 86 patients with BC who were divided into Luminal A (LA), Luminal B (LB), HER2 over-expression (H2), and triple-negative (TN). The CEUS qualitative and quantitative characteristics of BC with different molecular subtypes was explored, as well as the conventional ultrasound features. In addition, the diagnostic efficiency of CEUS quantitative parameters in differentiating molecular subtypes of BC was analyzed.RESULTS:Our study found that the Adler grade differed significantly among 4 molecular subtypes (P < .05). The enhancement speed, enhancement degree and size after enhancement of 4 molecular subtypes were statistically different (P < .05). The wash in slope (WIS), peak intensity (PI), and wash-in area under the curve (WiAUC) differed significantly among 4 subtypes (P < .05). The diagnostic efficiency of PI was better for detecting LA and H2 subtype with the areas under the receiver operating characteristic curve was 0.778 and 0.734, respectively.CONCLUSION:Different molecular subtypes of BC have different CEUS and conventional ultrasound characteristics. CEUS can provide valuable imaging basis for precise clinical diagnosis and individualized therapy of BC with different molecular subtypes.

Objective: Network analysis was used to explore the complex inter-relationships between social participation activities and depressive symptoms among the Chinese older population, and the differences in network structures among different genders, age groups, and urban-rural residency would be compared. Methods: Based on the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), 12,043 people aged 65 to 105 were included. The 10-item Center for Epidemiologic Studies Depression (CES-D) Scale was used to assess depressive symptoms and 10 types of social participation activities were collected, including housework, tai-chi, square dancing, visiting and interacting with friends, garden work, reading newspapers or books, raising domestic animals, playing cards or mahjong, watching TV or listening to radio, and organized social activities. R 4.2.1 software was used to estimate the network model and calculate strength and bridge strength. Results: 21.60% (2,601/12,043) of the participants had depressive symptoms. The total social participation score was negatively associated with depressive symptoms after adjusting for sociodemographic factors. The network of social participation and depressive symptoms showed that "D9 (Inability to get going)" and "S9 (Watching TV and/or listening to the radio)" had the highest strength within depressive symptoms and social participation communities, respectively, and "S1 (Housework)", "S9 (Watching TV and/or listening to the radio)", and "D5 (Hopelessness)" were the most prominent bridging nodes between the two communities. Most edges linking the two communities were negative. "S5 (Graden work) - D5 (Hopelessness)" and "S6 (Reading newspapers/books) - D4 (Everything was an effort)" were the top 2 strongest negative edges. Older females had significantly denser network structures than older males. Compared to older people aged 65-80, the age group 81-105 showed higher network global strength. Conclusions: This study provides novel insights into the complex relationships between social participation and depressive symptoms. Except for doing housework, other social participation activities were found to be protective for depression levels. Different nursing strategies should be taken to prevent and alleviate depressive symptoms for different genders and older people of different ages. (c) 2024 The authors. Published by Elsevier B.V. on behalf of the Chinese Nursing Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background Chatbots can provide immediate assistance tailored to patients' needs, making them suitable for sustained accompanying interventions. Nevertheless, there is currently no evidence regarding their acceptability by hypertensive patients and the factors influencing the acceptability in the real-world. Existing evaluation scales often focus solely on the technology itself, overlooking the patients' perspective. Utilizing mixed methods can offer a more comprehensive exploration of influencing factors, laying the groundwork for the future integration of artificial intelligence in chronic disease management practices. Methods The mixed methods will provide a holistic view to understand the effectiveness and acceptability of the intervention. Participants will either receive the standard primary health care or obtain a chatbot speaker. The speaker can provide timely reminders, on-demand consultations, personalized data recording, knowledge broadcasts, as well as entertainment features such as telling jokes. The quantitative part will be conducted as a quasi-randomized controlled trial in community in Beijing. And the convergent design will be adopted. When patients use the speaker for 1 month, scales will be used to measure patients' intention to use the speaker. At the same time, semi-structured interviews will be conducted to explore patients' feelings and influencing factors of using speakers. Data on socio-demography, physical examination, blood pressure, acceptability and self-management behavior will be collected at baseline, as well as 1,3,6, and 12 months later. Furthermore, the cloud database will continuously collect patients’ interactions with the speaker. The primary outcome is the efficacy of the chatbot on blood pressure control. The secondary outcome includes the acceptability of the chatbot speaker and the changes of self-management behavior. Discussion Artificial intelligence-based chatbot speaker not only caters to patients' self-management needs at home but also effectively organizes intricate and detailed knowledge system for patients with hypertension through a knowledge graph. Patients can promptly access information that aligns with their specific requirements, promoting proactive self-management and playing a crucial role in disease management. This study will serve as a foundation for the application of artificial intelligence technology in chronic disease management, paving the way for further exploration on enhancing the communicative impact of artificial intelligence technology. Trial registration: Biomedical Ethics Committee of Peking University: IRB00001052-21106, 2021/10/14; Clinical Trials: ChiCTR2100050578,2021/08/29.

Background: Large-for-size syndrome (LFSS) is an uncommon but potentially lethal complication following adult liver transplantation (LT). Reduced-size liver transplantation (RSLT) is considered a valuable alternative to delayed fascial closure or mesh closure for preventing LFSS. In this article, we report a successful adult-to-adult RSLT case with in situ right posterior graft sectionectomy using three-dimensional (3D) computer-assisted planning. This case is unique, as it employed preoperative planned in situ right posterior segmental resection (iRPS). Case Description: A short and slim, 69-year-old woman was admitted to Daping Hospital in January, 2023. The patient had previously been diagnosed with hepatitis B virus (HBV)-related hepatocellular carcinoma and acute-on-chronic liver failure. She had received 1 month of hepatoprotective and anti-HBV treatment before being admitted to Daping Hospital, and she had not suffered from any episodes of encephalopathy or upper gastrointestinal bleeding. The physical examination revealed moderate yellow staining of the skin and sclera, abdominal distension, shifting dullness, and pitting edema of the lower limbs. The laboratory test results revealed high serum total bilirubin (TBil) (121.2 mu mol/L) and a long prothrombin time (PT) (23.4 s). Computed tomography (CT) showed a 3.4 cm x 2.9 cm nodule in segment V of the liver without macrovascular invasion. Due to the patient's poor liver function, conventional anti-tumor therapies (e.g., surgical resection, transcatheter arterial chemoembolization, and radiofrequency ablation) could not be used, and LT was the only feasible treatment for the patient. The graft volume (GV) of the allocated liver was measured by computed tomography volumetry (CTV). The estimated graft-recipient weight ratio (GRWR) was 3.8%, and the estimated graft weight/right anteroposterior ratio (GW/RAP) was 120.2, which indicated that the donor liver size was severely mismatched with the recipient's abdominal cavity. After meticulous surgical planning using a 3D simulation implanting model, an in situ right posterior graft sectionectomy was performed, and the reduced-size graft was successfully implanted in the recipient. The post-transplant course was uneventful. At the 12-month follow-up, the patient had an excellent quality of life, and no signs of tumor recurrence. Conclusions: In situ right posterior graft sectionectomy is a feasible and effective strategy for preventing LFSS, especially if there is a size discrepancy between the donor liver anteroposterior dimensions and the recipient's lower right hemithorax. Accurate preoperative surgical planning is the key element in the success of the proposed size-reduction strategies.

Background To investigate the role and mechanism of liver parenchyma transection in accelerating the regeneration of future liver remnants in rats with portal vein ligation (PVL). Methods Rats were randomly divided into the PVL group (90% PVL at the caudate lobe, right lobe , left lateral lobe and left median lobe), associating liver partition and portal vein ligation for staged hepatectomy (portal vein ligation with complete liver parenchyma transection [ALPPS]) group (90% PVL with 80 to 90% liver parenchyma transection), PVL + partial liver partition (PLP) group (90% PVL with 30 to 50% liver parenchyma transection), PVL + partition in the ligated lobe (PLL) group (90% PVL with 40 to 60% liver parenchyma transection in the portal vein ligated lobe), PVL + partition in the remnant lobe (PRL) group (90% PVL with 40 to 60% liver parenchyma transection in the remnant lobe), PVL + radiofrequency ablation (RFA) group (90% PVL with splenic ablation) and sham operation (sham) group. The animals were killed at 4 time points of postoperative days 1, 3, 5, and 7. Six rats were killed at each time point, with 24 rats in each group. The weights of the future liver remnant and whole liver were measured. Serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin were analyzed by using an automatic biochemical analyzer. Serum tumor necrosis factor-α, interleukin-6, and hepatocyte growth factor were measured by enzyme-linked immunosorbent assay. The expression of cell proliferating nuclear antigen (Ki67) and phosphorylated histone H3 was detected by immunohistochemistry, and the positive rate was calculated. Results The ALPPS group displayed the highest FLR weight to body weight ratio compared with that of the other groups (P < .05), and the partial liver split (PVL + PLP) group also displayed higher remnant weight to body weight ratio than the ectopic liver split (PVL + PLL and PVL + PRL) groups (P < .05). During the first 7 days after surgery the cytokine levels of the ALPPS, PVL + PLP, PVL + PLL and PVL + PRL groups were comparable (P > .05). The PVL + PLP, PVL + PLL, PVL + PRL and PVL + RFA groups showed similar necrotic areas in the portal vein ligated lobe (P > .05). A hemodynamic study revealed that a liver split along the demarcation line could further increase the portal pressure of the FLR and both the split site and completeness were associated with portal hemodynamic alternations and liver hypertrophy. Extrahepatic organ injury (eg, spleen ablation) also has a significant impact on portal hemodynamics and liver regeneration. Conclusion Complete liver splitting along the demarcation line induced higher portal vein pressure and more rapid FLR hypertrophy than partial or ectopic liver splitting after PVL. The portal hemodynamic alterations after liver split rather than inflammatory cytokine release may be the major cause of ALPPS-induced rapid liver hypertrophy.