Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Immunomodulatory cancer therapy is witnessing the rise of viral immunotherapy. The oncolytic influenza A virus, although promising in preclinical investigations, remains to be implemented in clinical practice. Recent progress in genetic engineering, coupled with experiential insights, offers opportunities to enhance the therapeutic efficacy of the influenza A virus. This review explores the use of the influenza virus, its attenuated forms, and associated vaccines in cancer immunotherapy, highlighting their respective advantages and challenges. We further elucidate methods for engineering influenza viruses and innovative approaches to augment them with cytokines or immune checkpoint inhibitors, aiming to maximize their clinical impact. Our goal is to provide insights essential for refining influenza A virus-based viral tumor immunotherapies.
Humans ; Neoplasms/immunology* ; Immunotherapy/trends* ; Influenza A virus/immunology* ; Oncolytic Virotherapy/trends* ; Animals ; Cancer Vaccines/therapeutic use* ; Oncolytic Viruses ; Genetic Engineering ; Immune Checkpoint Inhibitors/therapeutic use*

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Objective:To evaluate the mediating effect of electrocardiographic (ECG) indicators in the association between short-term exposure to fine particulate matter (PM 2.5) and blood pressure and to explore the key PM 2.5 element constituents that produce the mediating effect. Methods:Based on a cross-sectional survey across 10 cities in the Beijing-Tianjin-Hebei region and surrounding areas, PM 2.5 and its element constituents were collected from the nearest air monitoring superstation. Blood pressure and ECG indicators of participants were obtained through physical examinations. A multivariate linear regression was used to evaluate the effect of short-term exposures to PM 2.5 on blood pressure. A mediation analysis was used to identify the mediating effect of ECG indicators in the association between exposure to PM 2.5 and its element constituents and blood pressure. Results:The age of the 1 793 participants was (65.1±13.3) years, and 885 (49.4%) were males. During the study period, the daily mean concentration of PM 2.5 was (70±45) μg/m 3, and the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP) were (139±20), (82±11), (101±13), and (57±17) mmHg (1 mmHg=0.133 kPa), respectively. The results of the multivariate linear regression showed that for every 10 μg/m 3 increase in PM 2.5 on the same day (lag 0), DBP increased by 0.15 (95% CI: 0.02-0.28) mmHg, and PP decreased 0.18 (95% CI: 0.36-0.01) mmHg. The exposure to 14 elemental constituents, such as Ga, Co and Se, was associated with an increase in DBP, while the exposure to 17 elemental constituents, such as Cs, Se and Ag, was associated with a decrease in PP. At lag 0, the PM 2.5-induced increase in DBP was mediated by the QRS interval (mediation percentage of 18.98%), and the PM 2.5-induced decrease in PP was mediated by the QT interval (mediation percentage of -6.31%). The exposure to K, Br, Pb, Zn, Ca, Co, Pd, Cu, and As constituents was associated with increases in DBP mediated by prolonged QRS interval. The exposure to Pb, Zn, K, and As constituents was associated with decreases in PP mediated by prolonged QRS interval. Conclusion:ECG indicators such as QRS interval may mediate the association between short-term exposure to PM 2.5 and its element constituents and blood pressure.

Objective:To assess the effect of short-term exposures to atmospheric fine particulate matter (PM 2.5) and its components on cognitive function in middle-aged and older people aged 40-89 and identify key components that affect cognitive function. Methods:From October 2018 to March 2019, a cross-sectional survey of middle-aged and older people aged 40-89 was conducted across 10 cities in Beijing-Tianjin-Hebei and neighboring regions of China. Data on PM 2.5 and its components were collected from the nearest air supermonitoring stations to the residential addresses. The cognitive function was assessed using the Min-Mental State Examination (MMSE) scale. Multiple linear regression models were used to assess the effect of short-term exposures to PM 2.5 and its components on cognitive function in middle-aged and older people. The restricted cubic spline function was used to fit the exposure-response relationship between different components and changes in MMSE scores. Results:The age of the 1 978 respondents was (65.1±13.4) years, and 976 (49.34%) were males. During the study period, the daily mean concentration of PM 2.5 was (71.2±43.2) μg/m 3, and the MMSE score was (28.2±3.7). The results of the multiple linear regression model showed that short-term exposures to PM 2.5 and its components were associated with cognitive decline in middle-aged and older people after adjusting for confounding factors, and the effect was higher at lag 0-28 days. For an interquartile range (64.3 μg/m 3) increase in PM 2.5 at lag 0-28 d, the MMSE score decreased by 5.91 (95% CI: 0.04, 11.77). For an interquartile range increase in organic carbon (OC), antimony (Sb), chromium (Cr), zinc (Zn), tin (Sn), and cadmium (Cd), the MMSE scores of middle-aged and older people decreased by 5.71 (95% CI: 1.69, 9.73), 4.67 (95% CI: 2.50, 6.84), 4.49 (95% CI: 1.05, 7.92), 3.65 (95% CI: 0.89, 6.42), 2.76 (95% CI: 1.22, 4.30), and 1.72 (95% CI: 0.53, 2.92). Conclusions:Short-term exposures to atmospheric PM 2.5 and its components (OC, Sb, Cr, Zn, Sn, and Cd) are associated with cognitive decline in middle-aged and older people.

Objective To compare the effects of preserving and releasing the inferior pulmonary ligament (IPL) during thoracoscopic right upper lobe apical segment resection for non-small cell lung cancer patients, and to explore appropriate management methods for intraoperative IPL. Methods According to the prospective and open principle, the patients with non-small cell lung cancer who underwent thoracoscopic right upper lobe apical segment resection in the Cardiothoracic Surgery Department of Ningbo Second Hospital from January 2020 to November 2022 were selected and divided into two groups: a release group (receiving IPL release during thoracoscopic right upper lobe apical segment resection) and a retention group (receiving the same right upper lobe apical segment resection, but retaining IPL during operation). The clinical data of the two groups were compared. Results A total of 70 patients were included in this study, including 33 males and 37 females, aged 35-76 years. There were 35 patients in the release group with an average age of (57.02±9.25) years; 35 patients in the retention group with an average age of (56.81±9.94) years. The surgical time in the release group was statistically longer than that in the retention group (P=0.017). There was no statistical difference between the two groups in terms of intraoperative bleeding, duration of postoperative air leakage, time to achieve lung recruitment, drainage flow rate of the chest tube, retention time of the chest tube, incidence of postoperative complications, postoperative hospitalization days, or residual cavity rate one month after the surgery (P>0.05). Conclusion Compared to releasing IPL during thoracoscopic right upper lobe apical segment resection, preserving IPL can simplify surgical procedures, shorten surgical time and reduce trauma, and does not increase postoperative adverse effects. This further reflects the concept of minimally invasive surgery and can be applied to clinical practice.

Objective:To observe and analyze the correlations between aqueous humor cytokine concentrations and disorganization of retinal inner layers (DRIL), as well as postoperative visual acuity, in patients with idiopathic epiretinal membrane (iERM).Methods:A prospective clinical study. From November 2022 to October 2024, 40 eyes of 40 patients diagnosed with iERM at Ophthalmology Center of Zhejiang Provincial People's Hospital (Affiliated People's Hospital) underwent cataract surgery alone or combined with pars plana vitrectomy (iERM group) were enrolled; 19 eyes of 19 patients undergoing cataract surgery alone during the same period served as the control group. All eyes underwent best-corrected visual acuity (BCVA) testing and swept-source optical coherence tomography (SS-OCT). BCVA was assessed using a logarithmic visual acuity chart and converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis. Central macular thickness (CMT) was measured using SS-OCT. The iERM group was further subdivided into DRIL-positive and DRIL-negative subgroups (21 eyes and 19 eyes, respectively), based on the presence or absence of DRIL. Aqueous humor samples were collected preoperatively from eyes in both the iERM and control groups. Concentrations of transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, platelet-derived growth factor (PDGF)-AB, hepatocyte growth factor, fibroblast growth factor, vascular endothelial growth factor-A (VEGF-A), placental growth factor (PLGF), glial cell line-derived neurotrophic factor (GDNF), intercellular adhesion molecule-1 (ICAM-1), angiopoietin (Ang)-1, Ang-2, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. Follow-up examinations using the same equipment and methods were performed at 1 month postoperatively. Aqueous cytokine levels were compared between the iERM group, control group, DRIL-positive subgroup, and DRIL-negative subgroup. Correlations between aqueous cytokine levels in the iERM group and BCVA or CMT were also analyzed. Intergroup comparisons utilized the Mann-Whitney U test; correlations between variables were assessed using Spearman's rank correlation analysis. Results:Compared to the control group, the iERM group exhibited significantly higher aqueous concentrations of TGF-β1, TGF-β3, PDGF-AB, PLGF, GDNF, ICAM-1, Ang-1, and TNF-α ( P<0.05). Compared to the DRIL-negative subgroup, the DRIL-positive subgroup showed significantly elevated aqueous concentrations of TGF-β3, PDGF-AB, PLGF, GDNF, ICAM-1, Ang-1, Ang-2, TNF-α, and IL-6 ( P<0.05). Significant differences were observed in logMAR BCVA ( P=0.028) and CMT ( P<0.001) within the iERM group between preoperative and 1-month postoperative measurements. LogMAR BCVA differed significantly between the DRIL-positive and DRIL-negative subgroups ( P=0.048). Correlation analysis revealed that baseline aqueous levels of VEGF-A and IL-6 in eyes with DRIL were positively correlated with postoperative BCVA ( r=0.324, 0.452; P=0.042, 0.003). No significant correlation was found between CMT and any cytokine ( P>0.05). Conclusions:Aqueous humor cytokines are closely associated with DRIL in iERM patients. IL-6 and VEGF-A may serve as potential predictive biomarkers for early postoperative visual recovery.

Estrogen, through binding to its receptors in the female endometrium, promotes the proliferation, differentiation, and angiogenesis of endometrial stromal cells, thereby playing a critical role in endometrial injury repair, regeneration, and the prevention and treatment of intrauterine adhesions. Currently, various estrogen-based pharmaceutical formulations are applied in clinical practice, and the development of related products is progressively advancing. This review systematically outlines the etiology of endometrial injury and the mechanisms by which estrogen facilitates endometrial repair and regeneration. Furthermore, it highlights recent research progress and clinical applications of estrogen-based therapies in endometrial regeneration, aiming to provide a valuable reference for relevant scientific research and clinical practice.

Background::An evidence gap still exists regarding the efficacy and safety of tegoprazan in patients with erosive esophagitis (EE) in China. This study aimed to verify the efficacy and safety of tegoprazan vs. esomeprazole in patients with EE in China. Methods::This study was a multicenter, randomized, double-blind, parallel, active-controlled, non-inferiority phase III trial of patients with EE randomized 1:1 to tegoprazan 50 mg/day vs. esomeprazole 40 mg/day. This study was conducted in 32 sites between October 24, 2018 and October 18, 2019. The primary endpoint was the cumulative endoscopic healing rate at week 8. The secondary endpoint included endoscopic healing rate at week 4, changes in the reflux disease questionnaire (RDQ) and gastroesophageal reflux disease health-related quality of life (GERD-HRQL) scores, and symptom improvement. Results::A total of 261 patients were randomized: 132 to the tegoprazan group and 129 to the esomeprazole group. The cumulative endoscopic healing rate at 8 weeks in the tegoprazan group was non-inferior to that of the esomeprazole group (91.1% vs. 92.8%, difference: -1.7%, 95% confidence interval [CI]: -8.5%, 5.0%, P = 0.008). There were no statistically significant differences in the changes in RDQ (total, severity, and frequency) and GERD-HRQL scores between the two groups (all P >0.05). The percentages of days without symptoms, including daytime and nighttime symptoms based on patients' diaries, were similar between the two groups (all P >0.05). In the tegoprazan and esomeprazole groups, 71.5% (93/130) and 61.7% (79/128) of the participants reported adverse events (AEs), 2.3% and 0 experienced serious AEs, while 70.0% and 60.2% had treatment-emergent AEs, respectively. Conclusion::Tegoprazan 50 mg/day demonstrated non-inferior efficacy in healing EE, symptom improvement, and quality of life, and it has similar tolerability compared with esomeprazole 40 mg/day.

Objective:To evaluate the mediating effect of electrocardiographic (ECG) indicators in the association between short-term exposure to fine particulate matter (PM 2.5) and blood pressure and to explore the key PM 2.5 element constituents that produce the mediating effect. Methods:Based on a cross-sectional survey across 10 cities in the Beijing-Tianjin-Hebei region and surrounding areas, PM 2.5 and its element constituents were collected from the nearest air monitoring superstation. Blood pressure and ECG indicators of participants were obtained through physical examinations. A multivariate linear regression was used to evaluate the effect of short-term exposures to PM 2.5 on blood pressure. A mediation analysis was used to identify the mediating effect of ECG indicators in the association between exposure to PM 2.5 and its element constituents and blood pressure. Results:The age of the 1 793 participants was (65.1±13.3) years, and 885 (49.4%) were males. During the study period, the daily mean concentration of PM 2.5 was (70±45) μg/m 3, and the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP) were (139±20), (82±11), (101±13), and (57±17) mmHg (1 mmHg=0.133 kPa), respectively. The results of the multivariate linear regression showed that for every 10 μg/m 3 increase in PM 2.5 on the same day (lag 0), DBP increased by 0.15 (95% CI: 0.02-0.28) mmHg, and PP decreased 0.18 (95% CI: 0.36-0.01) mmHg. The exposure to 14 elemental constituents, such as Ga, Co and Se, was associated with an increase in DBP, while the exposure to 17 elemental constituents, such as Cs, Se and Ag, was associated with a decrease in PP. At lag 0, the PM 2.5-induced increase in DBP was mediated by the QRS interval (mediation percentage of 18.98%), and the PM 2.5-induced decrease in PP was mediated by the QT interval (mediation percentage of -6.31%). The exposure to K, Br, Pb, Zn, Ca, Co, Pd, Cu, and As constituents was associated with increases in DBP mediated by prolonged QRS interval. The exposure to Pb, Zn, K, and As constituents was associated with decreases in PP mediated by prolonged QRS interval. Conclusion:ECG indicators such as QRS interval may mediate the association between short-term exposure to PM 2.5 and its element constituents and blood pressure.