Biomedical subjects

Wei Guo

Publications and source records attributed to Wei Guo.

9 recordsLinked to original sources

PubMed2026

An AI-assisted Clinical Decision Support System for Green Classification of Cystocele on Dynamic Transperineal Ultrasound.

Green classification of cystocele on dynamic transperineal ultrasound (TPUS) remains operator-dependent because it requires manual frame selection and landmark-based assessment of the Valsalva maneuver. We developed a workflow-oriented AI-assisted clinical decision support system for automated urethrovesical junction localization and dynamic Green classification and prospectively evaluated its standalone and reader-support performance. This diagnostic accuracy and reader study included 881 patients from a tertiary referral hospital, comprising a retrospective development cohort (n = 688) and an independent prospective test cohort (n = 193). A nested subset of 67 prospective patients was used for a reader study involving two junior and two intermediate radiologists under unaided and AI-assisted conditions. In the complete prospective test cohort, Green-AttGRU achieved a macro-averaged AUC of 0.939 (95% CI, 0.897-0.971) and an overall accuracy of 0.902 (95% CI, 0.860-0.943). In the reader study, overall accuracy increased from 0.761 to 0.821 without AI to 0.851-0.881 with AI, while macro-F1 increased from 0.660 to 0.777 to 0.820-0.860. Overall inter-reader agreement increased from a Fleiss' κ of 0.453 to 0.786, and pooled median interpretation time decreased from 26.7 s to 9.9 s. These findings support the preliminary feasibility of the system as a workflow-oriented decision-support tool for dynamic TPUS interpretation.

Humans↗

PubMed2026

Rumen DNA virome plasticity and viral metabolic potential are associated with seasonal adaptation in grazing yak and cattle on the Qinghai-Tibet Plateau.

BACKGROUND: As a diverse and abundant component of the rumen ecosystem, viruses interact with other microorganisms and are thought to influence microbial metabolism and host productivity. However, how the rumen virome responds to seasonal fluctuations in extreme environments remains poorly understood. Here, metagenomic analyses were used to investigate temporal dynamics of viral diversity, functional potential, and virus-host associations in the rumen virome of yak and cattle on the Qinghai-Tibet Plateau across warm and cold seasons. RESULTS: Rumen viral communities exhibited pronounced seasonal variation in both yaks and cattle, with higher alpha diversity observed during the cold season than in the warm season. Across seasons, the yak rumen virome showed greater alpha diversity and community stability than that of cattle. In total, 27,353 temperate and 31,976 virulent viral operational taxonomic units (vOTUs) were identified, predominantly belonging to the class Caudoviricetes. These viruses were linked to microbial hosts spanning 24 bacterial and 8 archaeal phyla, with Bacteroidota and Bacillota representing the dominant lineages. Virus-host associations were more numerous in the cold season and showed distinct host-specific patterns between yaks and cattle. Cold-season virome exhibited reduced diversity of anti-defense genes and enrichment of auxiliary metabolic genes (AMGs) associated with fatty acid metabolism and hemicellulose degradation. Notably, greater divergence between yaks and cattle was observed during the cold season: the yak rumen virome was enriched in pathways related to amino acid, lipid, and energy metabolism, as well as cellulose-degrading CAZyme families, whereas the cattle rumen virome showed enrichment in general carbohydrate metabolism and replication and repair processes. CONCLUSION: Seasonal plasticity of rumen DNA virome and pronounced interspecific divergence between yaks and cattle provide insight into their distinct microbial processes in the harsh environment of the Qinghai-Tibet Plateau. These findings suggest that the rumen DNA virome exhibits complex ecological and functional responses to seasonal variation and may be associated with host-microbiome interactions and nutrient utilization under environmental stress. This study highlights the ecological relevance of rumen viral genomes in understanding virus-microbiome interactions, microbial adaptation, and nutrient utilization in high-altitude ruminants.

Auxiliary metabolic genes↗

PubMed2026

Genomic and One Health insights into Vibrio parahaemolyticus from environmental, seafood and clinical sources.

Vibrio parahaemolyticus is a leading cause of seafood-borne gastroenteritis worldwide, with climate warming facilitating its spread to high-latitude areas. In this study, we analyzed 212 genomes of environmental and seafood-associated isolates collected from seven cities in Zhejiang Province, China (2019-2024), alongside 228 clinical genomes from public databases. The 212 isolates were assigned to 172 sequence types (STs), with ST490 being the most frequent (5/212, 2.36%). Forty-four serotypes were identified, dominated by OL3:KUT (12.68%). High ST and serotype diversity were observed across different sample types and sources, with median pairwise single nucleotide polymorphisms (SNPs) ranging from 57,431 to 58,378, indicating comparable genetic diversity across groups. All isolates carried tlh and T3SS1 but lacked tdh and T3SS2. Resistance rates against ampicillin and cefazolin were 54.72% (116/212) and 44.34% (94/212), respectively, with multidrug resistance (MDR) detected in nine isolates, predominantly from seafood (7/9). A total of 63 distinct antimicrobial resistance genes (ARGs) spanning seven classes were identified. Isolates from aquaculture farms and wet markets exhibited greater resistance category diversity and higher ARG carriage than those from coastal or riverine sites. In contrast, the 228 clinical isolates harbored only 25 ARGs across two classes, with a significantly lower proportion of isolates carrying multiple ARG classes (0.44% vs. 6.13%, P < 0.001). Human isolates formed tighter phylogenetic clusters, although a minority were closely related to environmental/foodborne strains. Overall, our findings demonstrate the genetic diversity and resistance potential of V. parahaemolyticus across environmental, seafood, and clinical sources, highlighting the importance of the One Health approach to comprehensive public health risk assessment.

Vibrio parahaemolyticus↗

PubMed2026

A phase 2 study of encorafenib in combination with binimetinib for Chinese participants with BRAFV600E mutated metastatic non-small cell lung cancer: Results from the OCEAN II study.

PURPOSE: The ongoing OCEAN II study (ClinicalTrials.gov identifier: NCT05195632) evaluates encorafenib in combination with binimetinib (E+B) in Chinese participants with BRAFV600E-mutated metastatic non-small cell lung cancer (NSCLC). METHODS: Participants with metastatic unresectable stage IV BRAFV600E-mutated NSCLC (treatment-naïve or with prior systemic therapy excluding BRAF/MEK-inhibitors), were enrolled in a phase 2 study with two parts: safety lead-in (SLI) and pivotal part (PP). Participants received daily oral encorafenib (450mg) and twice daily oral binimetinib (90mg total). Primary endpoints were dose-limiting toxicities (DLT) during SLI and confirmed objective response rate by independent central review (cORR-ICR) during PP. Secondary endpoints were other measures of efficacy, safety, and pharmacokinetics. RESULTS: In total, 63 participants were enrolled. One DLT (non-serious Grade 3 lipase increased) during SLI considered possibly related to E+B resolved without intervention, supporting initiation of PP. Pre-defined statistical efficacy criteria on the first 50 participants were met. In the main analysis, cORR-ICRwas59% (95%CI 45-72). At a later ad hoc analysis, cORR-ICR was 61% (95%CI 47-74), disease control rate 87% (95%CI 75-95). Medians (95%CI) were, time-to-response 1.8 months, duration of response 17.5 months, progression-free survival 13.8 months (7.5-not estimable), overall survival 27.9 months (14.7-30.0). 98.4% of participants experienced ≥1 treatment-related TEAE, and 55.6% had any Grade ≥3 TEAE. Nine (14.3%) participants discontinued any drug due to adverse events. CONCLUSION: These data confirm the clinical benefit of E+B in Chinese participants with BRAFV600E-mNSCLC, a population with distinct genomic and disease characteristics. No new safety concerns were identified in Chinese participants.

Adult↗

PubMed2026

Epigenetic safety of in vitro maturation in PCOS: genome-wide DNA methylation profiling of cord blood from a randomized controlled trial.

BACKGROUND: In vitro maturation (IVM) provides a safer alternative to conventional in vitro fertilization (IVF) for women with polycystic ovary syndrome (PCOS) by mitigating the risk of ovarian hyperstimulation. However, concerns persist regarding whether IVM perturbs epigenetic reprogramming in the offspring. Current evidence is constrained by candidate-gene approaches or a lack of parental controls. This study aimed to evaluate the genome-wide DNA methylation safety of IVM compared with conventional IVF using a rigorous trio-based design. METHODS: This secondary epigenetic analysis was nested within a randomized controlled trial (RCT) (ClinicalTrials.gov: NCT03463772). We included 10 nuclear families (trios), comprising five IVM-conceived and five IVF-conceived singleton offspring alongside their biological parents. Both groups utilized a uniform freeze-only single-blastocyst transfer strategy to minimize hormonal confounding. Genomic DNA from umbilical cord blood (UCB) and parental peripheral blood was analyzed using reduced representation bisulfite sequencing (RRBS). Genome-wide methylation patterns and differentially methylated regions (DMRs) were subsequently compared between the groups. RESULTS: Clinical characteristics were comparable between the IVM and IVF groups. Genome-wide analyses demonstrated high concordance in UCB methylation patterns, revealing no significant differences in global CpG methylation levels or distributions across key genomic features (promoters, CpG islands, and gene bodies). Only three rare DMRs were identified in UCB (representing ~ 0.0001% of the genome), none of which mapped to imprinted or developmentally critical loci. Furthermore, methylation variability remained consistent between the groups. CONCLUSIONS: Our findings provide robust mechanistic evidence supporting the epigenetic safety of IVM. The remarkable stability of the neonatal methylome confirms that specific IVM conditions do not compromise early developmental programming, thereby endorsing IVM as a safe and viable alternative for women with PCOS. TRIAL REGISTRATION: ClinicalTrials.gov registry, NCT03463772. Registered on March 13, 2018.

Humans↗

PubMed2026

40 Hz light flickering alleviates chronic pain via adenosine signaling in the retina-amygdala pathway.

Chronic pain affects over 20% of the global population, yet frontline treatments remain limited in efficacy and are often hampered by serious side effects. In search of novel and effective neuromodulation alternatives, we discovered that 40 Hz flickering light effectively alleviates inflammatory and neuropathic pain in mice. We identified the retina-central amygdala (CeA) pathway as a critical conduit for the analgesic effects of 40 Hz flickering light. Using circuit-specific manipulations, we demonstrated that activation of the retina-CeA pathway is both sufficient to mimic and necessary to mediate the analgesic outcomes of 40 Hz light stimulation. In terms of mechanism, we found that 40 Hz light flickering significantly increases extracellular adenosine levels in the CeA. Local pharmacological blockade of equilibrative nucleoside transporters prevented this adenosine increase and abolished the analgesic effects of 40 Hz light flickering, whereas focal adenosine infusion phenocopied the light-induced analgesia. Both interventions required A2A receptor signaling to suppress nociceptive responses. Furthermore, we found that hyperalgesia could be destabilized in the CeA and reversed by 40 Hz light stimulation or adenosine infusion, mirroring memory reconsolidation processes and implicating the CeA as a key locus for pain memory erasure. Collectively, our findings demonstrate the multifaceted therapeutic benefits of 40 Hz light flickering as a novel non-invasive approach for pain management and reveal a distinct retina-CeA circuit and adenosine signaling mechanism for control of chronic pain and pain memory.

Animals↗

PubMed2026

Machine Learning-Based Preoperative Predicting TERT Promoter Mutation and EGFR Gene Amplification Phenotype in IDH Wild-Type Glioblastoma Using Advanced MR Habitat Imaging.

BACKGROUND AND PURPOSE: The telomerase reverse transcriptase (TERT) gene promoter mutation is a crucial factor for identifying an isocitrate dehydrogenase (IDH) wild-type glioblastoma with poor prognosis, and the epidermal growth factor receptor (EGFR) amplification may be a potential prognostic factor. The purpose of this study was to investigate the value of the tumor habitats imaging model on advanced MRI in predicting TERT promoter mutation and EGFR gene amplification phenotype of IDH wild-type glioblastoma. MATERIALS AND METHODS: One hundred seventy-nine patients with pretreatment conventional MRI, DWI, and DSC-PWI were included. The data were divided into the training set (n=112), test set (n=29), and time-independent validation set (n=38). Based on the ADC and CBV map, the solid tumor area was split into several habitat subregions using the k-means clustering algorithm (hypovascular hypercellular area, hypervascular area, and hypovascular hypocellular area). In the training set, TERT promoter mutation and EGFR gene amplification phenotype prediction models were constructed using the random forest method. The reliability of prediction models was validated in the test and the time-independent validation sets. Receiver operating characteristic (ROC) curve analysis, calibration curve, and decision curve analysis (DCA) were used. RESULTS: The area under the curve (AUC) of the training, test, and validation sets of the TERT promoter prediction model was 0.877, 0.783, and 0.796, respectively. The accuracy of the TERT promoter prediction model was 82.1%, 75.9%, and 76.3%, respectively. The AUCs of the 3 sets for the EGFR gene amplification status prediction model were 0.877, 0.784, and 0.878, respectively. The accuracy of the EGFR gene amplification status prediction model was 79.5%, 75.9%, and 89.5%, respectively. Moreover, the prediction probability of these models was in good agreement with the actual result. CONCLUSIONS: The tumor habitat imaging model based on advanced MRI was useful for accurately predicting TERT promoter mutation and EGFR amplification status in IDH wild-type glioblastoma.

Humans↗

PubMed2025

GATA2 promotes cervical cancer progression under the transcriptional activation of TRIP4.

The continued rise in recurrence and mortality rates of cervical cancer suggests the need to find novel therapeutic targets. Previous studies suggest that TRIP4 acts as a transcription factor to regulate cervical carcinogenesis and progression. Our aim was to explore whether the key downstream genes of TRIP4 functions same as TRIP4 in promoting cervical cancer development. We analyzed and confirmed the downstream targets of TRIP4 by RNA sequencing in cervical cancer cells with TRIP4 knockdown. The expression correlation between TRIP4 and GATA2 and the effect of GATA2 on cervical cancer cell growth were determined respectively by Western Blot, Scratch, Spheroid, and MTT analyses. Pulldown and ChIP experiments were performed to analyze the binding of TRIP4 to the promoter of GATA2. The clinical significance of GATA2 and TRIP4 expression in cervical cancer patients was analyzed by tissue microarray staining. GATA2 was highly expressed in cervical cancer tissues. Knockdown of GATA2 inhibited the growth, metastasis and stemness of cervical cancer cells and sensitized cervical cancer cells to radiation therapy. The inhibitory effect of TRIP4 knockdown on cervical cancer cells was rescued by GATA2 overexpression. Furthermore, TRIP4 could bind to the specific GATA2 promoter region, thereby activating its transcription. Clinical tissue microarray analysis indicated that the expression of TRIP4 and GATA2 was positively correlated, and high expression of both predicted a poor prognosis in cervical cancer patients. Our study demonstrated that GATA2 functions as the key downstream target of TRIP4 to promote cervical cancer progression and effective intervention of TRIP4/GATA2 signaling is expected to be developed as potential cervical cancer therapeutic strategy.

Humans↗

PubMed2021

Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma.

Little is known about the transcriptomic plasticity and adaptive mechanisms of circulating tumor cells (CTCs) during hematogeneous dissemination. Here we interrogate the transcriptome of 113 single CTCs from 4 different vascular sites, including hepatic vein (HV), peripheral artery (PA), peripheral vein (PV) and portal vein (PoV) using single-cell full-length RNA sequencing in hepatocellular carcinoma (HCC) patients. We reveal that the transcriptional dynamics of CTCs were associated with stress response, cell cycle and immune-evasion signaling during hematogeneous transportation. Besides, we identify chemokine CCL5 as an important mediator for CTC immune evasion. Mechanistically, overexpression of CCL5 in CTCs is transcriptionally regulated by p38-MAX signaling, which recruites regulatory T cells (Tregs) to facilitate immune escape and metastatic seeding of CTCs. Collectively, our results reveal a previously unappreciated spatial heterogeneity and an immune-escape mechanism of CTC, which may aid in designing new anti-metastasis therapeutic strategies in HCC.

Aged↗