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.

Immunoglobulin A (IgA) nephropathy is a globally prevalent type of primary glomerulonephritis, characterized by complex symptoms and diverse clinical manifestations. The internationally recognized " multiple hit hypothesis" explains the systemic immune disease features of IgA nephropathy. However, current treatment strategies primarily focus on local pathological changes, inadequately addressing its complex systemic mechanisms. The " qi cycle in round" theory, an integral concept of the academic thought of HUANG Yuanyu, a prominent medical expert from the Qing Dynasty, offers a concise and insightful framework for understanding complex pathologies. For example, this theory provides valuable insights for elucidating the pathogenesis of IgA nephropathy and guiding its clinical management by simplifying intricate systemic processes. This study applies the " qi cycle in round" theory to postulate that patients with IgA nephropathy experience disrupted qi flow owing to spleen-stomach qi deficiency and dampness-heat accumulation. These imbalances manifest as internal symptoms, such as diarrhea; external vulnerability to illness; upper body symptoms, like sore throat; and lower body symptoms, such as hematuria and proteinuria. Pathologically, the condition is characterized by immune complex deposition. This article also emphasizes strategies that prioritize tonifying spleen-stomach qi to enhance the pivotal functions of transportation and transformation. Regulating qi and relieving stagnation are emphasized to harmonize ascending and descending dynamics. Additionally, eliminating turbidity and unblocking collaterals are highlighted to promote qi transformation. These approaches aim to restore the harmonious operation of organ qi dynamics and harmonious qi transformation functions. This study aims to provide a reference for syndrome differentiation and IgA nephropathy treatment using traditional Chinese medicine based on the " qi cycle in round" theory.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To construct a nanoparticle vaccine displaying the prefusion F (preF) protein of respiratory syncytial virus (RSV) using the I53-50 protein nanoparticle platform, and to systematically evaluate its immunogenicity and protective efficacy.Methods:The RSV preF trimer antigen was genetically fused to I53-50A and assembled in vitro with I53-50B to form preF-I53-50 nanoparticles, theoretically displaying 20 preF antigens per particle. The structure and purity were characterized by size-exclusion chromatography, SDS-PAGE, and negative-stain electron microscopy. BALB/c mice were intramuscularly immunized with varying doses (1 μg or 5 μg) of preF antigen or an equimolar amount of preF-I53-50 nanoparticles. Humoral immunity, B-cell responses, and protective efficacy were assessed following intranasal viral challenge.Results:The preF-I53-50 nanoparticles self-assembled into spherical structures (50-60 nm in diameter) with uniformly arrayed antigens. The nanoparticle vaccine enhanced RSV-specific IgG1 and IgG2a antibody responses, promoting a Th1-biased immune profile. At equimolar preF doses, the neutralizing antibody titers induced by 1 μg and 5 μg nanoparticle formulations were 2.8-fold and 2.3-fold higher, respectively, than those elicited by preF alone ( P<0.05). Notably, even the low-dose nanoparticle group outperformed the high-dose preF group (1.6-fold increase). Viral challenge experiments demonstrated that preF-I53-50 effectively suppressed pulmonary viral replication, mitigated pathological damage, and induced stronger germinal center and memory B-cell responses, suggesting enhanced B-cell affinity maturation and long-term immune memory. Conclusion:The preF-I53-50 vaccine improves the immunogenicity and protective efficacy of RSV preF through multivalent antigen display.

Objective:To investigate the influencing factors and perinatal outcomes associated with monozygotic twins (MZT) following elective single embryo transfer (eSET) via in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Methods:A retrospective cohort study was conducted on 12 079 patients who achieved pregnancy after undergoing IVF/ICSI-eSET at Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between January 2015 and September 2023. Patients were stratified into two groups based on ultrasound findings 30 d post-transfer: singleton pregnancy group and MZT pregnancy group. Finally, 300 MZT and 1 500 single pregnancies, which were randomly matched according to 1∶5 were included by study period. General patients' characteristics, embryo-related factors, and perinatal outcomes were compared between the two groups. A multivariate logistic regression model was employed to identify risk factors for MZT after single embryo transfer, adjusting for potential confounding variables.Results:The incidence of twin pregnancy following single embryo transfer was 2.48% (300/12 079), which was higher than that of naturally conceived monozygotic twin pregnancy. No significant difference was found in baseline characteristics between the two groups (all P>0.05). The blastocyst transfer rate was higher in the MZT pregnancy group [93.3% (280/300)] than in the singleton pregnancy group [88.8% (1 332/1 500), P=0.022]. Multivariate logistic regression analysis also showed that blastocyst transfer was associated with an increased risk of MZT ( OR=0.552, P=0.016, 95% CI: 0.341-0.894). Analysis of blastocyst cycles showed that the risk of MZT was higher when transferring high-quality blastocysts [79.6% (223/280) vs. 67.8% (903/1 332), P<0.001], where as a trophectoderm (TE) grading of C [20.4% (57/280) vs. 32.2% (429/1 332), P<0.001] had a lower risk of MZT. After adjusting for confounding factors, the risk of MZT was found to increase with the transfer of blastocysts with a B-grade inner cell mass (ICM) ( OR=0.601, P=0.001, 95% CI: 0.442-0.819) and A/B grade TE (grade A: OR=2.951, P<0.001, 95% CI: 1.980-4.399; grade B: OR=1.840, P<0.001, 95% CI: 1.315-2.576). The risk of complications during pregnancy [47.7% (143/300) vs. 19.3% (289/1 500), P<0.001], preterm labor [55.1% (140/254) vs. 7.4% (101/1 368), P<0.001], and the risk of stillbirth [3.7% (11/300) vs. 1.5% (22/1 500), P=0.016] were significantly higher in the MZT pregnancy group than in the singleton pregnancy group. Conclusion:Assisted reproductive technology may contribute to the risk of MZT. Transfer of blastocysts, particularly those with loose ICM arrangement and dense TE arrangement, appears to increase the risk of MZT in patients undergoing eSET.

With excellent energy spectrum imaging capabilities and high spatial resolution,photon counting detector(PCD)-CT is gradually applied in imaging evaluation on abdominal organs,including livers,pancreas,kidneys,gastrointestinal tract and so on,significantly improve the detection of small abdominal lesions and low-contrast abnormalities while reducing both iodine contrast agents dosage and radiation exposure.The technical characteristics and clinical applications of PCD-CT,as well as its advancements in abdominal imaging were reviewed in this article.

Objective:To measure the distance between the fetal bladder neck and the rectal end using prenatal MRI and analyze the developmental patterns of this distance and the gender differences in the second and third trimesters of pregnancy.Methods:This retrospective cohort study involved fetuses born at Guangzhou Women and Children's Medical Center, Guangzhou Medical University after regular prenatal examinations from January 2019 to December 2022 and confirmed to have typical anorectal structures after birth. These fetuses had undergone prenatal MRI examinations for reasons other than abdominal issues. The morphology of the fetuses' colons, rectums, and bladders was observed, and the vertical distance between the bladder neck and the rectal end was measured on sagittal T1weighted imaging. Differences in the distance between male and female fetuses were analyzed. The fetuses were divided into five groups based on their gestational age at the time of MRI examination (23-24 weeks, >24-26 weeks, >26-28 weeks, >28- 30 weeks, and >30-32 weeks), and the changes in the distance with gestational age were analyzed. Statistical analysis was performed using t-test, Kruskal-Wallis test, and Spearman correlation analysis. Pairwise comparisons among multiple groups were conducted using the Bonferroni method. Results:(1) A total of 142 fetuses were included in this study, all of which were singletons, with 73 males (51.4%) and 69 females (48.6%). The gestational age at the MRI examination was 28 weeks (26-30 weeks). (2) All fetuses had meconium filling the entire rectum and colon, with the rectal end located 0.570-2.610 cm below the bladder neck. (3) The distance between the bladder neck and the rectal end was shorter in male fetuses than in female fetuses [(1.140±0.261) vs. (1.519±0.405) cm, t=－6.58, P<0.001]. (4) In female fetuses, four pairs of groups showed statistically significant differences in the distance (23-24 weeks group vs. >26-28 weeks, >28- 30 weeks, and >30-32 weeks groups, and >24-26 weeks group vs. >30-32 weeks group). However, only two groups of male fetuses (23-24 weeks group vs. >28-30 weeks group) had statistically significant differences in the distance (all P<0.005). (5) The distance was moderately correlated with gestational age in male fetuses ( r=0.42, P<0.001), but they were strongly correlated in female fetuses ( r=0.66, P<0.001). Conclusions:The distance between the bladder neck and the rectal end in fetuses shows certain developmental patterns and gender differences in pregnancy's second and third trimesters. The correlation between the value and gestational age is stronger in female fetuses.

Catheter-based percutaneous coronary intervention has become a crucial approach for treating obstructive coronary artery disease and is widely applied in clinical practice.Although the new generation of drug-eluting stents(DES)has significantly reduced the incidence of post-procedur-al restenosis and improved long-term clinical outcomes,in-stent restenosis(ISR)remains one of the key challenges affecting the long-term efficacy of percutaneous coronary intervention.Recent studies have demonstrated that DES still have certain inherent limitations.From the metallic stent platform,drug coating to the polymer carrier,each component may exert varying degrees of biological effects on the vascular intima.Optical coherence tomography(OCT),as a high-resolution intravascular imaging technique,has shown significant value in the mechanism research,etiological diagnosis,and clinical classification of ISR.It can clearly identify the tissue composition and morphological characteristics of ISR,providing a precise basis for the formulation of individualized treatment strategies.This review aimed to systematically search the existing literature,comprehensively review the clinical and patho-logical features of ISR after DES implantation,focus on the OCT-based ISR classification system,and summarize the current treatment strategies and latest advances for ISR.

OBJECTIVE: To explore the possible mechanism by which the "Zhibian" (BL54) toward "Shuidao" (ST28) acupuncture improves ovarian function in mice with poor ovarian response (POR) by observing its effect on gut microbiota. METHODS: A total of 35 SPF-grade C57BL/6 female mice were screened for normal estrous cycles using vaginal smears, and 30 mice were selected. Ten mice were assigned to the blank group, while the remaining mice were used to establish the POR model by intragastric administration of tripterygium wilfordii suspension. The successfully modeled mice were randomly divided into a model group and an acupuncture group, with 10 mice in each group. After modeling, the acupuncture group received the "Zhibian" (BL54) toward "Shuidao" (ST28) acupuncture method once daily for 20 minutes per session. Ovulation induction began the day after the intervention, and samples were collected after ovulation induction. Vaginal cytology was used to observe estrous cycle changes, and the number of oocytes obtained, ovarian wet weight, and ovarian index were recorded. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH) were detected using ELISA. HE staining was used to observe ovarian histology. Gut microbiota was analyzed using 16S rRNA gene sequencing technology. Western blot was used to detect the relative protein expression levels of Occludin and zonula occludens-1 (ZO-1) in colonic tissue. Correlation analysis was conducted among serum hormone indexes, the number of oocytes obtained, ovarian index and gut microbiota. RESULTS: Compared with the blank group, the model group showed a higher estrous cycle disorder rate (P<0.01), increased serum FSH and LH levels, and a higher LH/FSH ratio (P<0.01), while the number of oocytes obtained, ovarian wet weight, ovarian index, and serum E2 and AMH levels were significantly reduced (P<0.01). Compared with the model group, the acupuncture group showed a lower estrous cycle disorder rate (P<0.01), decreased serum FSH and LH levels, and a lower LH/FSH ratio (P<0.01), along with an increased number of oocytes obtained, higher ovarian wet weight, ovarian index, and elevated serum AMH and E2 levels (P<0.01, P<0.05). The blank group had a large number of well-developed primordial follicles, with abundant and closely arranged follicles at various stages. In the model group, there was a significant increase in the number of atretic follicles, a reduction in the number of follicles at various stages, and loosely arranged ovarian tissue. Compared with the blank group, the model group showed a significant decrease in the number of normal follicles (P<0.01) and an increase in the number of atretic follicles (P<0.01). The acupuncture group showed a reduction in atretic follicles and an increase in the number of follicles at various stages compared with the model group, with a significant increase in normal follicles (P<0.01) and a decrease in atretic follicles (P<0.01). Compared with the blank group, the model group exhibited reduced gut microbiota diversity and richness, with significantly lower Chao1 and Shannon indices (P<0.01), and a greater clustering distance from the blank group. The model group also showed an increase in the relative abundance of Firmicutes_D, Verrucomicrobiota, Paramuribaculum, Dubosiella, and Muribaculum (P<0.01, P<0.05), while the relative abundance of Firmicutes_A and the relative protein expression of Occludin and ZO-1 in colonic tissue were decreased (P<0.01). Compared with the model group, the acupuncture group showed improved gut microbiota diversity and richness, with increased Chao1 and Shannon indices (P<0.05), and a clustering distance closer to the blank group. The acupuncture group exhibited reduced relative abundance of Firmicutes_D, Verrucomicrobiota, and Muribaculum (P<0.05, P<0.01), while the relative abundance of Firmicutes_A and the relative protein expression of Occludin and ZO-1 were significantly increased (P<0.01, P<0.05). Correlation analysis indicated a relationship between gut microbiota and serum hormone indicators, as well as the ovarian index. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that the metabolic pathways of the intersecting species were related to amino acid biosynthesis and nucleotide metabolism. CONCLUSION The "Zhibian" (BL54) toward "Shuidao" (ST28) acupuncture method improves ovarian function in POR mice, and its mechanism may be related to regulating gut microbiota structure and maintaining intestinal barrier homeostasis.
Animals ; Female ; Gastrointestinal Microbiome ; Mice ; Acupuncture Therapy ; Mice, Inbred C57BL ; Humans ; Ovary/physiopathology* ; Acupuncture Points ; Follicle Stimulating Hormone/metabolism* ; Luteinizing Hormone/metabolism* ; Estrous Cycle ; Anti-Mullerian Hormone/blood*

The efficacy of Xiangmei Pills on rats with ulcerative colitis(UC) was investigated by characterizing the spectrum of the active chemical components of Xiangmei Pills. Rapid identification and classification of the main chemical components were performed,and the therapeutic effects of Xiangmei Pills on the proteins and intestinal flora of UC rats were analyzed to explore the mechanism of its action in treating UC. Fifty SD rats were acclimatized to feeding for 3 d and randomly divided into blank group, model group,mesalazine group(0. 4 g·kg~(-1)), low-dose group of Xiangmei Pills(1. 89 g·kg~(-1)), and high-dose group of Xiangmei Pills(5. 67 g·kg~(-1)), with 10 rats in each group. 5% dextrose sodium sulfate(DSS) was given by gavage to induce the male SD rat model with UC,and the corresponding medicinal solution was given by gavage after 10 days, respectively. The therapeutic effect of Xiangmei Pills on rats with UC was evaluated according to body mass, disease activity index(DAI), and hematoxylin-eosin(HE) staining, and the histopathological changes in the colon were observed. Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) technique was used to rapidly and accurately identify the main chemical constituents of Xiangmei Pills. Immunohistochemistry was used to detect the expression of aryl hydrocarbon receptor(AhR),interferon-γ(IFN-γ), mucin-2(MUC-2), and cytochrome P450 1A1(CYP1A1) in colon tissue. Interleukin-22(IL-22) expression in colon tissue was detected by immunofluorescence. The 16S r DNA high-throughput sequencing technique was used to study the modulatory effects of Xiangmei Pills on the intestinal flora structure of rats with UC. Pharmacodynamic results showed that compared with that of the blank group, the colon tissue of the model group was congested, and ulcers were visible in the mucosa; compared with that in the model group, the histopathology of the colon of the rats with UC in the groups of Xiangmei Pills were improved, with scattered ulcers and reduced inflammatory cell infiltration. Chemical analysis showed that a total of 45 components were identified by mass spectrometry information, including 15 phenolic acids, 8 coumarins, 15 organic acids, 3 amino acids, 2 flavonoids, and 2 other components. Compared with those in the blank group, the levels of Ah R, CYP1A1, MUC-2, and IL-22 proteins in the colon tissue of rats in the model group were significantly decreased, and the level of IFN-γ protein was significantly increased; the intestinal flora of rats in the model group was disorganized, with a decrease in the abundance of the flora; the relative abundance of Bacteroidetes,unclassified genera of Ascomycetes, Prevotella of the Prevotella family, and Prevotella decreased significantly, and that of Firmicutes decreased, but the difference was not statistically significant. The relative abundance of Bacteroidetes, Bifidobacterium, and Lactobacillus increased significantly. Compared with those of the model group, the levels of Ah R, CYP1A1, MUC-2, and IL-22proteins in the colonic tissue of the groups of Xiangmei Pills were significantly higher, and the levels of IFN-γ proteins were significantly lower. The recovery of the intestinal flora was accelerated, and the diversity of the intestinal flora was significantly increased. The relative abundance of Bacteroidetes was significantly increased, and that of unclassified genera of Ascomycetes,Lactobacillus, Prevotella of the Prevotella family, and Prevotella was significantly increased. The relative abundance of Bacteroidetes and Bifidobacterium was significantly decreased. This study demonstrated that Xiangmei Pills can effectively treat UC, mainly through the phenolic acid and organic acid components to stimulate the intestinal barrier, regulate protein expression and the relative abundance and diversity of intestinal flora, and play a role in the treatment of UC.
Animals ; Colitis, Ulcerative/metabolism* ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Male ; Rats ; Gastrointestinal Microbiome/genetics* ; Chromatography, High Pressure Liquid ; Humans ; Mass Spectrometry ; RNA, Ribosomal, 16S/genetics* ; Bacteria/drug effects*