Acquired immunodeficiency syndrome (AIDS)/human immunodeficiency virus (HIV) patients experience significant increase in their survival and decline in the mortality with the advent of antiretroviral therapy (ART). Nonetheless, ART alone still cannot completely cure AIDS/HIV patients. Furthermore, the virus remains latent in resting CD4+T cells for extended periods, posing a continuous threat to AIDS/HIV patients. Immune checkpoint blockades (ICBs), as a promising immunotherapy, inaugurate new pathways for AIDS/HIV cure or remission given their capability to break down the latency limit of HIV, and promote the regeneration and activation of HIV-specific T cells. However, not all AIDS/HIV patients respond to immune checkpoint inhibitors (ICIs), similar to that encountered in cancer patients, accompanied by the risk of severe immune-related adverse events (irAEs) in some cases. Accordingly, the present study was conducted to explore the possibility of personalized medicine tailored to the host discrepancy, with purposes of achieving better treatment outcomes, higher objective response rates, and fewer irAEs. Strategies for ICIs based on individual differences are documented to be conducive to improving therapeutic outcomes for patients. Therefore, this study intended to improving the therapeutic efficacy of ICIs in AIDS/HIV patients within the context of precision immunotherapy, including monotherapy and combination strategies, as well as the application of predictive biomarkers.

In the context of the rising global prevalence of obesity, traditional intervention measures have proven insufficient to meet the demands of personalized and sustainable health management, necessitating the exploration of innovative solutions through innovative technologies. This study explores how advanced digital technologies, including Internet of Things (IoT) and Artificial Intelligence (AI), can manage weight and enhance full-lifecycle health in individuals with obesity under simulated high-altitude hypoxic conditions (HC). The findings suggest that integrating simulated HC with digital health technologies offers a novel and safe approach to obesity rehabilitation. By leveraging environmental stimuli, real-time monitoring through wearable devices, and intelligent evaluation using large language models (LLMs), this method enables more scientific weight loss, prevents rebound weight gain, and fosters proactive healthy lifestyles, significantly improving weight control outcomes for individuals with obesity. Future research should evaluate the efficacy of simulated HC in weight management and its long-term impact on obesity control. Establishing an integrated framework that combines simulated HC, lifestyle interventions, and smart health ecosystems is crucial for advancing rehabilitative healthcare and addressing the global burden of obesity through digital innovation.

The prognostic significance of preoperative platelet counts among patients with hepatocellular carcinoma (HCC) undergoing curative resection remains controversial. The objective of the current study was to investigate the impact of preoperative platelet count on long-term outcomes after HCC resection. Patients who underwent curative-intent resection for HCC between 2000 and 2021 at 10 hepatobiliary centers in China were retrospectively analyzed. Patients were categorized based on platelet count within 2 weeks before surgery: thrombocytopenia (< 100 × 10⁹/L), normal platelet count (100-299 × 10⁹/L), and thrombocytosis (≥ 300 × 10⁹/L). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). Among 3,116 patients, 655 (21.0%) had thrombocytopenia, 2,374 (76.2%) had normal platelet counts, and 87 (2.8%) had thrombocytosis. The 5-year OS was 52.7%, 56.0%, and 40.2% for thrombocytopenia, normal platelet count, and thrombocytosis groups, respectively (p < 0.001 among the three groups); the corresponding 5-year RFS was 39.3%, 39.3%, and 26.9%, respectively (p = 0.001 among the three groups). Multivariable analysis identified both thrombocytopenia (HR 1.215, 95% CI 1.045-1.413, p = 0.011) and thrombocytosis (HR 1.307, 95% CI 1.130-1.511, p < 0.001) as independent risk factors for worse OS, and thrombocytosis was independently associated with worse RFS (HR 1.523, 95% CI 1.196-1.939, p = 0.001). Both thrombocytopenia and thrombocytosis were associated with worse survival after HCC resection, with thrombocytosis also predicting higher risk of recurrence. Routine preoperative platelet count may serve as a valuable and practical prognostic marker for risk stratification among patients with HCC undergoing resection.

Hepatocellular carcinoma (HCC) risk factors and incidence vary globally, but men generally have higher incidence than women. Men also tend to have a worse prognosis in terms of survival period and pathological characteristics. Furthermore, there are notable gender differences in treatment strategies and drug responses. While traditional risk factors such as hepatitis B virus, hepatitis C virus, alcohol consumption, and metabolic syndrome contribute to these differences, the underlying molecular mechanisms remain partly understood. Recent research has focused on elucidating the roles of sex hormones, DNA damage and repair pathways, immune microenvironments, and genetic/epigenetic factors in driving gender-specific disparities. For instance, estrogen receptor signaling has been shown to suppress HCC progression, whereas androgen receptor signaling promotes tumor development. Additionally, immune cells such as tumor-associated macrophages and regulatory T cells exhibit gender-specific patterns, with males typically showing higher levels of immunosuppressive cells. Omics analyses, including genomics, transcriptomics, and proteomics, have further revealed sex-specific differences in gene expression, protein interactions, and metabolic pathways. Despite these advances, significant gaps remain in understanding the interplay between environmental, hormonal, and genetic factors in shaping gender disparities in HCC. Future research should prioritize the identification of novel molecular targets, the development of gender-specific therapeutic strategies, and the integration of multi-omics data to address these disparities. Addressing these challenges will be critical for improving diagnostic, prognostic, and therapeutic outcomes in HCC patients of both sexes.

Stroke remains a leading cause of mortality and long-term disability worldwide, frequently resulting in impairments in motor control, cognition, and emotional regulation. Conventional rehabilitation approaches, while partially effective, often lack individualization and yield suboptimal outcomes. In recent years, brain-computer interface (BCI) technology has emerged as a promising neurorehabilitation tool by decoding neural signals and providing real-time feedback to enhance neuroplasticity. This review systematically explores the use of BCI systems in post-stroke rehabilitation, focusing on three core domains: motor function, cognitive capacity, and emotional regulation. This review outlines the neurophysiological principles underpinning BCI-based motor rehabilitation, including neurofeedback training, Hebbian plasticity, and multimodal feedback strategies. It then examines recent advances in upper limb and gait recovery using BCI integrated with functional electrical stimulation (FES), robotics, and virtual reality (VR). Moreover, it highlights BCI's potential in cognitive and language rehabilitation through EEG-based neurofeedback and the integration of artificial intelligence (AI) and immersive VR environments. In addition, it discusses the role of BCI in monitoring and regulating post-stroke emotional disorders via closed-loop systems. While promising, BCI technologies face challenges related to signal accuracy, device portability, and clinical validation. Future research should prioritize multimodal integration, AI-driven personalization, and large-scale randomized trials to establish long-term efficacy. This review underscores BCI's transformative potential in delivering intelligent, personalized, and cross-domain rehabilitation solutions for stroke survivors.

This study investigates the use of machine learning (ML) models combined with a Synthetic Minority Over-sampling Technique (SMOTE) and its variants to predict perioperative pressure injuries (PIs) in an imbalanced dataset. PIs are a significant healthcare problem, often leading to prolonged hospitalization and increased medical costs. Conventional risk assessment scales are limited in their ability to predict PIs accurately, prompting the exploration of ML techniques to address this challenge.We utilized data from 7,292 patients admitted to a tertiary care hospital in Shanghai between May 2017 and July 2023, with a final dataset of 2,972 patients, including 158 with PIs. Seven ML algorithms—Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), Extreme Gradient Boosting (XGBoost), Extra Trees (ET), K-Nearest Neighbors (KNN), and Decision Trees (DT)—were used in conjunction with SMOTE, SMOTE+ENN, Borderline-SMOTE, ADASYN, and GAN to balance the dataset and improve model performance.Results revealed significant improvements in model performance when SMOTE and its variants were used. For instance, the XGBoost model hadan AUC of 0.996 with SMOTE, compared to 0.800 on raw data. SMOTE+ENN and Borderline-SMOTE further enhanced the models' ability to identify minority classes. External validation indicatedthat XGBoost, RF, and ET exhibited the highest stability and accuracy, with XGBoost having an AUC of 0.977. SHAP analysis revealed that factors such as anesthesia grade, age, and serum albumin levels significantly influenced model predictions.In conclusion, integrating SMOTE with ML algorithms effectively addressed a data imbalance and improved the prediction of perioperative PIs. Future work should focus on refining SMOTE techniques and exploring their application to larger, multi-center datasets to enhance the generalizability of these findings, and especially for diseaseswith a lowincidence.

The pre-mRNAs splicing is important mechanisms of hepatocellular carcinoma (HCC) progression. Hence, this study aimed to explore the function and corresponding mechanisms of small nuclear ribonucleoprotein polypeptide A (SNRPA), a vital RNAs splicing molecule, in HCC. Here, the University of Alabama at Birmingham CANcer data analysis portal (UALCAN), western blotting, and immunohistochemistry indicated that SNRPA levels were elevated in HCC tissues. Moreover, high expression of SNRPA was correlated with unfavorable clinicopathologic features and poor survival in HCC patients. A series of in vitro and in vivo gain/loss-of-function experiments reported that SNRPA promoted the proliferation of HCC cells. Integrated nanopore full-length cDNA sequencing and RNA-binding protein immunoprecipitation sequencing revealed that B7 homologue 6 (B7-H6) was a potential target of SNRPA. Subsequently, western blotting and flow cytometry showed that SNRPA activated B7-H6-STAT3/AKT signaling axis in HCC cells with promotion of G1-S transition in the cell cycle and inhibition of cell apoptosis. Mechanistically, RNA-binding protein immunoprecipitation and polymerase chain reaction with using exon-exon and exon-intron junction primers revealed that SNRPA facilitated B7-H6 pre-mRNA maturation by binding to it directly and contributing to its intron 2 splicing. Moreover, drug sensitivity test found that SNRPA induced HCC cell resistance to lenvatinib. Finally, restoration experiments demonstrated that the effects of SNRPA on HCC cells relied on B7- H6 expression. Taken together, SNRPA promotes HCC growth and lenvatinib resistance via B7-H6-STAT3/AKT axis through facilitating B7-H6 pre-mRNA maturation by maintaining its intron 2 splicing. Thus, SNRPA may be a promising target for HCC therapy and lenvatinib resistance reversion.

Colorectal cancer liver metastasis (CRLM) remains the leading cause of mortality among colorectal cancer (CRC) patients, with more than half eventually developing hepatic metastases. Achieving long-term survival in CRLM necessitates early detection, robust stratification, and precision treatment tailored to individual classifications. These processes encompass critical aspects such as tumor staging, predictive modeling of therapeutic responses, and risk stratification for survival outcomes. The rapid evolution of artificial intelligence (AI) has ushered in unprecedented opportunities to address these challenges, offering transformative potential for clinical oncology. This review summarizes the current methodologies for CRLM grading and classification, alongside a detailed discussion of the machine learning models commonly used in oncology and AI-driven applications. It also highlights recent advances in using AI to refine CRLM subtyping and precision medicine approaches, underscoring the indispensable role of interdisciplinary collaboration between clinical oncology and the computational sciences in driving innovation and improving patient outcomes in metastatic colorectal cancer.

Breast cancer liver metastasis (BCLM) presents a critical challenge in breast cancer treatment and has substantial epidemiological and clinical significance. Receptor status is pivotal in managing both primary breast cancer and its liver metastases. Moreover, shifts in these statuses can have a profound impact on patient treatment strategies and prognoses. Research has indicated that there is significant heterogeneity in receptor status between primary breast cancer and liver metastases. This variation may be influenced by a multitude of factors, such as therapeutic pressure, inherent tumor heterogeneity, clonal evolution, and the unique microenvironment of the liver. Changes in the receptor status of BCLM are crucial for adjusting treatment strategies, and liver biopsy plays an important role in the treatment process. Directions for future research targeting changes in receptor status include in-depth study of molecular mechanisms, combined treatment strategies for receptor status reversal, development of artificial intelligence deep learning models to predict receptor status in liver metastases, and clinical research on new drug development and combination therapies. That research will provide more precise treatment strategies for patients with BCLM and improve their prognosis.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by β-amyloid accumulation, tau pathology, and impaired metabolic waste clearance. Recent evidence suggests that meningeal lymphatic vessels (MLVs) contribute significantly to the drainage of cerebrospinal and interstitial fluid. Deep cervical lymphaticovenous anastomosis (LVA), a microsurgical technique designed to enhance this drainage, has been proposed as a potential therapeutic strategy for AD. Preliminary findings from exploratory studies in China indicate possible cognitive and biomarker improvements, but current evidence is limited by small sample sizes, non-randomized designs, and methodological variability. Without standardized protocols and rigorous clinical validation, the broader applicability of LVA remains uncertain. Further investigation through multicenter, controlled trials is essential to objectively assessing its safety, efficacy, and clinical relevance in the management of AD.

One of the challenges of laparoscopic liver resection (LLR) is the exposure of the surgical field. We propose a new surgical approach to better expose the right liver, stretching of the ligamentum teres hepatis (SLTH), and we evaluated its clinical feasibility and limitations through a study analyzing relevant cases. Clinicopathologic data on patients who underwent laparoscopic right partial hepatectomy (LRPH) at our center were retrospectively collected, and subjects were 276 patients with liver space-occupying lesions who met the selection criteria and who underwent the new surgical approach (SLTH) or the conventional surgical approach (no stretching of the ligamentum teres hepatis, or NSLTH). After 1:1 propensity score matching (PSM), 102 patients in each cohort were selected for further analysis. There were no significant differences in the operating time or the duration of postoperative hospitalization between the SLTH cohort and the NSLTH cohort. The duration of detachment of the hepatic parenchyma and the duration of hepatic portal occlusion were significantly shorter in the SLTH cohort than in the NSLTH cohort. The intraoperative blood loss in the SLTH cohort was significantly less than that in the NSLTH cohort. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly lower in the SLTH cohort than in the NSLTH cohort on day 5 postoperatively. Results confirmed that SLTH is a simple, safe, effective, and highly reproducible technique for the treatment of LRPH. SLTH may help to perform LRPH by increasing the level of laparoscopic exposure of the right liver and reducing bleeding and operating time.

The human gut microbiome is increasingly recognized as important to health and disease, influencing immune function, metabolism, mental health, and chronic illnesses. Two widely used, cost-effective, and fast approaches for analyzing gut microbial communities are shallow shotgun metagenomic sequencing (SSMS) and full-length 16S rDNA sequencing. This study compares these methods across 43 stool samples, revealing notable differences in taxonomic and species-level detection. At the genus level, Bacteroides was most abundant in both methods, with Faecalibacterium showing similar trends but Prevotella was more abundant in full-length 16S rDNA. Genera such as Alistipes and Akkermansia were more frequently detected by full-length 16S rDNA, whereas Eubacterium and Roseburia were more prevalent in SSMS. At the species level, Faecalibacterium prausnitzii, a key indicator of gut health, was abundant across both datasets, while Bacteroides vulgatus was more frequently detected by SSMS. Species within Parabacteroides and Bacteroides were primarily detected by 16S rDNA, contrasting with higher SSMS detection of Prevotella copri and Oscillibacter valericigenes. LEfSe analysis identified 18 species (9 species in each method) with significantly different detection between methods, underscoring the impact of methodological choice on microbial diversity and abundance. Differences in classification databases, such as Ribosomal Database Project (RDP) for 16S rDNA and Kraken2 for SSMS, further highlight the influence of database selection on outcomes. These findings emphasize the importance of carefully selecting sequencing methods and bioinformatics tools in microbiome research, as each approach demonstrates unique strengths and limitations in capturing microbial diversity and relative abundances.

Despite the continued high prevalence of colorectal cancer in the Western world, recent years have witnessed a decline in its mortality rate, largely attributable to the sustained advancement of multimodal treatment modalities for metastatic patients. One persisting issue is lack of consensus between different centres and multidisciplinary teams regarding definition of resectability, the duration of chemotherapy treatment, and surgical strategy. This narrative review outlines current multimodal treatment of patients with colon cancer metastatic to the liver and/or lung in different clinical scenarios. Currently, there are multiple multimodal strategies that can be employed to enhance resectability in these patients. These include novel and sophisticated target therapies (such as novel immunotherapeutic modalities and micro RNAs), complex resections utilising parenchyma-sparing techniques, liver transplantation, and cytoreductive strategies in patients for whom a curative option is not feasible. It is the responsibility of the scientific community to establish standardised protocols across different centres, based on the most recent evidence, while maintaining a high degree of personalisation of treatment for each individual patient. It seems likely that artificial intelligence (AI) will play a significant role in achieving this goal.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, neuroinflammation, and endoplasmic reticulum (ER) stress. In recent years, exosomes have garnered significant attention as a potential therapeutic tool for neurodegenerative diseases. This study, for the first time, investigates the neuroprotective effects of exosomes derived from olfactory mucosa mesenchymal stem cells (OM-MSCs-Exos) in AD and further explore the potential role of low-density lipoprotein receptor-related protein 1 (LRP1) in this process. Using an Aβ1-42-induced AD mouse model, we observed that OM-MSCs-Exos significantly improved cognitive function in behavioral tests, reduced neuroinflammatory responses, alleviated ER stress, and decreased neuronal apoptosis. Further analysis revealed that OM-MSCs-Exos exert neuroprotective effects by modulating the activation of microglia and astrocytes and influencing the ER stress response, a process that may involve LRP1. Although these findings support the potential neuroprotective effects of OM-MSCs-Exos, further studies are required to explore their long-term stability, dose dependency, and immunogenicity to assess their feasibility for clinical applications.

Distant metastasis after hepatectomy for hepatocellular carcinoma (HCC) significantly impairs long-term outcome. This study aimed to identify patterns, risk factors, and develop a prediction model for distant metastasis at first recurrence following HCC resection. This multi-center retrospective study included patients undergoing curative hepatectomy for HCC. Risk factors for distant metastasis were identified using Cox regression. A nomogram was constructed and validated using the concordance index (C-index) and calibration curves. Among 2,705 patients, 1,507 experienced recurrence, with 342 (22.7 per cent) developing distant metastasis. Common metastatic sites included extrahepatic vessels (36.2 per cent), lungs (26.0 per cent), and lymph nodes (20.8 per cent). Patients with distant metastasis had significantly worse 5-year overall survival compared to those with intrahepatic recurrence (9.1 versus 41.1 per cent, p < 0.001). Independent risk factors included preoperative tumor rupture, tumor size over 5.0 cm, multiple tumors, satellite nodules, macro- and microvascular invasion, narrow resection margin, and intraoperative blood transfusion. The nomogram demonstrated excellent discrimination (C-index > 0.85) and accurately stratified patients into three risk categories. In conclusion, distant metastasis at first recurrence following HCC resection was associated with poor prognosis. The proposed nomogram facilitates accurate prediction of distant metastasis, potentially informing personalized postoperative monitoring and interventions for high-risk patients.

Dermatologic toxicities associated with targeted therapies may impact drug intolerance and predict drug response, among which rash is most frequently reported and well delineated. However, the profile and effect of non-rash dermatologic toxicity are not fully understood. We identified stage-IV non-small cell lung cancer patients diagnosed at Mayo Clinic in 2006-2019 and systematically analyzed demographics, targeted agents, toxicity, response, and survival outcomes of patients who received targeted therapy. Five toxicity subgroups-none, only non-rash dermatologic, concurrent non-rash and rash (concurrent) dermatologic, only rash, and others-were compared; multivariable survival analyses employed Cox Proportional Hazard models. This study included 533 patients who had taken targeted therapies: 36 (6.8%) had no toxicity, 26 (4.9%) only non-rash dermatologic, 193 (36.2%) only rash, 134 (25.1%) concurrent dermatologic, 144 (27.0%) other toxicities. Non-rash dermatologic toxicities predominately included xerosis (12.8%), pruritus (8.5%), paronychia (7.0%). Rash was the most frequent (59.4%) and the earliest occurring (21 median onset days [MOD]) dermatologic toxicity; paronychia was the latest (69 MOD) occurring. In 329 epidermal growth factor receptor inhibitors-treated patients with dermatologic toxicity, mild toxicity occurred the most frequently in patients with only non-rash (81.8%), then those with only rash (64.8%), and the least in the concurrent (50.4%, P=0.013). Patients with concurrent dermatologic toxicities had a significantly higher response rate (67.9%) than those with only non-rash (53.8%) or only rash (41.1%, p < 0.001). Multivariable analysis demonstrated concurrent dermatologic toxicity independently predicted a lower risk of death (harzard ratio [HR] 0.48 [0.30-0.77], p < 0.001). Compared to rash, non-rash dermatologic toxicity might be a stronger predictor of better treatment response and longer survival in patients who received targeted therapy.

Immune checkpoint inhibitors (ICIs) have been widely used in various types of cancer, but they have also led to a significant number of adverse events, including ICI-induced immune-mediated hepatitis (IMH). This study aimed to explore the risk factors for IMH in patients treated with ICIs and to develop and validate a new nomogram model to predict the risk of IMH. Detailed information was collected between January 1, 2020, and December 31, 2023. Univariate logistic regression analysis was used to assess the impact of each clinical variable on the occurrence of IMH, followed by stepwise multivariate logistic regression analysis to determine independent risk factors for IMH. A nomogram model was constructed based on the results of the multivariate analysis. The performance of the nomogram model was evaluated via the area under the receiver operating characteristic curve (AUC), calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) analysis. A total of 216 (8.82%) patients developed IMH. According to stepwise multivariate logistic analysis, hepatic metastasis, the TNM stage, the WBC count, LYM, ALT, TBIL, ALB, GLB, and ADA were identified as risk factors for IMH. The AUC for the nomogram model was 0.817 in the training set and 0.737 in the validation set. The calibration curves, DCA results, and CIC results indicated that the nomogram model had good predictive accuracy and clinical utility. The nomogram model is intuitive and straightforward, making it highly suitable for rapid assessment of the risk of IMH in patients receiving ICI therapy in clinical practice. Implementing this model enables early adoption of preventive and therapeutic strategies, ultimately reducing the likelihood of immune-related adverse events (IRAEs), and especially IMH.

Syphilis, a chronic infection caused by Treponema pallidum, is experiencing a global resurgence, posing significant public health challenges. This study examined the escalating trends of syphilis in the United States, China, and some other countries highlighting the impact of the COVID-19 pandemic, changes in sexual behavior, coinfection with the other infectious diseases such as AIDs, and the role of public health funding. The analysis revealed a stark increase in syphilis cases, particularly among high-risk groups such as men who have sex with men (MSM). China's National Syphilis Control Program (NSCP), initiated in 2010, is a comprehensive approach to syphilis management that incorporates health education, access to testing and treatment, partner notification, safe sex promotion, community interventions, and stigma reduction. The success of the NSCP in reducing early syphilis incidence rates and congenital syphilis in Guangdong Province, that may be served as a model for international syphilis control efforts. This study highlights the necessity for targeted public health interventions and the importance of robust healthcare infrastructure in combating the syphilis epidemic.