1.Liquid biopsy in hepatocellular carcinoma: Challenges, advances, and clinical implications
Jaeho PARK ; Yi-Te LEE ; Vatche G. AGOPIAN ; Jessica S LIU ; Ekaterina K. KOLTSOVA ; Sungyong YOU ; Yazhen ZHU ; Hsian-Rong TSENG ; Ju Dong YANG
Clinical and Molecular Hepatology 2025;31(Suppl):S255-S284
Hepatocellular carcinoma (HCC) is an aggressive primary liver malignancy often diagnosed at an advanced stage, resulting in a poor prognosis. Accurate risk stratification and early detection of HCC are critical unmet needs for improving outcomes. Several blood-based biomarkers and imaging tests are available for early detection, prediction, and monitoring of HCC. However, serum protein biomarkers such as alpha-fetoprotein have shown relatively low sensitivity, leading to inaccurate performance. Imaging studies also face limitations related to suboptimal accuracy, high cost, and limited implementation. Recently, liquid biopsy techniques have gained attention for addressing these unmet needs. Liquid biopsy is non-invasive and provides more objective readouts, requiring less reliance on healthcare professional’s skills compared to imaging. Circulating tumor cells, cell-free DNA, and extracellular vesicles are targeted in liquid biopsies as novel biomarkers for HCC. Despite their potential, there are debates regarding the role of these novel biomarkers in the HCC care continuum. This review article aims to discuss the technical challenges, recent technical advancements, advantages and disadvantages of these liquid biopsies, as well as their current clinical application and future directions of liquid biopsy in HCC.
2.A convenient research strategy for functional verification of epigenetic regulators during spermatogenesis.
Shan LI ; Ying YUAN ; Ke-Yu ZHANG ; Yi-Dan GUO ; Lu-Tong WANG ; Xiao-Yuan ZHANG ; Shu ZHANG ; Qi YAN ; Rong ZHANG ; Jie CHEN ; Feng-Tang YANG ; Jing-Rui LI
Asian Journal of Andrology 2025;27(2):261-267
Spermatogenesis is a fundamental process that requires a tightly controlled epigenetic event in spermatogonial stem cells (SSCs). The mechanisms underlying the transition from SSCs to sperm are largely unknown. Most studies utilize gene knockout mice to explain the mechanisms. However, the production of genetically engineered mice is costly and time-consuming. In this study, we presented a convenient research strategy using an RNA interference (RNAi) and testicular transplantation approach. Histone H3 lysine 9 (H3K9) methylation was dynamically regulated during spermatogenesis. As Jumonji domain-containing protein 1A (JMJD1A) and Jumonji domain-containing protein 2C (JMJD2C) demethylases catalyze histone H3 lysine 9 dimethylation (H3K9me2), we firstly analyzed the expression profile of the two demethylases and then investigated their function. Using the convenient research strategy, we showed that normal spermatogenesis is disrupted due to the downregulated expression of both demethylases. These results suggest that this strategy might be a simple and alternative approach for analyzing spermatogenesis relative to the gene knockout mice strategy.
Spermatogenesis/physiology*
;
Animals
;
Male
;
Mice
;
Epigenesis, Genetic
;
Jumonji Domain-Containing Histone Demethylases/metabolism*
;
Histones/metabolism*
;
RNA Interference
;
Testis/metabolism*
;
Methylation
;
Mice, Knockout
;
Histone Demethylases
3.Explanation and interpretation of blood transfusion provisions for children with hematological diseases in the national health standard "Guideline for pediatric transfusion".
Ming-Yi ZHAO ; Rong HUANG ; Rong GUI ; Qing-Nan HE ; Ming-Yan HEI ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jin-Ping LIU ; Jing WANG ; Zhi-Li SHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Ming-Hua YANG
Chinese Journal of Contemporary Pediatrics 2025;27(1):18-25
To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion is one of the most commonly used supportive treatments for children with hematological diseases. This guideline provides guidance and recommendations for blood transfusions in children with aplastic anemia, thalassemia, autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, acute leukemia, myelodysplastic syndromes, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura. This article presents the evidence and interpretation of the blood transfusion provisions for children with hematological diseases in the "Guideline for pediatric transfusion", aiming to assist in the understanding and implementing the blood transfusion section of this guideline.
Humans
;
Child
;
Hematologic Diseases/therapy*
;
Blood Transfusion/standards*
;
Practice Guidelines as Topic
4.Explanation and interpretation of the compilation of blood transfusion provisions for children undergoing hematopoietic stem cell transplantation in the national health standard "Guideline for pediatric transfusion".
Rong HUANG ; Qing-Nan HE ; Ming-Yan HEI ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jin-Ping LIU ; Jing WANG ; Zhi-Li SHAO ; Ming-Yi ZHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Rong GUI ; Ming-Hua YANG
Chinese Journal of Contemporary Pediatrics 2025;27(2):139-143
To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion for children undergoing hematopoietic stem cell transplantation is highly complex and challenging. This guideline provides recommendations on transfusion thresholds and the selection of blood components for these children. This article presents the evidence and interpretation of the transfusion provisions for children undergoing hematopoietic stem cell transplantation, with the aim of enhancing the understanding and implementation of the "Guideline for pediatric transfusion".
Humans
;
Hematopoietic Stem Cell Transplantation
;
Child
;
Blood Transfusion/standards*
;
Practice Guidelines as Topic
5.Explanation and interpretation of blood transfusion provisions for critically ill and severely bleeding pediatric patients in the national health standard "Guideline for pediatric transfusion".
Rong HUANG ; Qing-Nan HE ; Ming-Yan HEI ; Ming-Hua YANG ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jin-Ping LIU ; Jing WANG ; Zhi-Li SHAO ; Ming-Yi ZHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Rong GUI
Chinese Journal of Contemporary Pediatrics 2025;27(4):395-403
To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Critically ill children often present with anemia and have a higher demand for transfusions compared to other pediatric patients. This guideline provides guidance and recommendations for blood transfusions in cases of general critical illness, septic shock, acute brain injury, extracorporeal membrane oxygenation, non-life-threatening bleeding, and hemorrhagic shock. This article interprets the background and evidence of the blood transfusion provisions for critically ill and severely bleeding children in the "Guideline for pediatric transfusion", aiming to enhance understanding and implementation of this aspect of the guidelines. Citation:Chinese Journal of Contemporary Pediatrics, 2025, 27(4): 395-403.
Humans
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Critical Illness
;
Blood Transfusion/standards*
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Child
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Hemorrhage/therapy*
;
Practice Guidelines as Topic
6.Explanation and interpretation of blood transfusion provisions for children undergoing cardiac surgery in the national health standard "Guideline for pediatric transfusion".
Rong HUANG ; Qing-Nan HE ; Ming-Yan HEI ; Ming-Hua YANG ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jing WANG ; Zhi-Li SHAO ; Ming-Yi ZHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Rong GUI ; Jin-Ping LIU
Chinese Journal of Contemporary Pediatrics 2025;27(7):778-785
To guide clinical blood transfusion practices in pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Children undergoing cardiac surgery are at high risk of bleeding, and the causes of perioperative anemia and coagulation disorders in neonates and children are complex and varied, often necessitating the transfusion of allogeneic blood components. This guideline provides direction and recommendations for specific measures in blood management for children undergoing cardiac surgery before, during, and after surgery. This article interprets the background and evidence for the formulation of the blood transfusion provisions for children undergoing cardiac surgery, hoping to facilitate the understanding and implementation of this guideline.
Humans
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Cardiac Surgical Procedures
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Blood Transfusion/standards*
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Child
;
Practice Guidelines as Topic
7.Clinical and genetic analysis of a patient with FSIP2 compound heterozygous variants causing multiple morphological abnormalities of sperm flagella.
Yao-Qi CHEN ; Li-Qi XU ; Yi-Bo DAI ; Liang-Yu YAO ; Shen-Ming YANG ; Lu-Yu HUANG ; Xi YANG ; Yi YU ; Jing-Ming YANG ; Ke-Rong WU
National Journal of Andrology 2025;31(5):395-402
OBJECTIVE:
The aim of this study is to analyze the clinical features and genetic etiology of a patient with multiple morphological abnormalities of the sperm flagella (MMAF) retrospectively.
METHODS:
A severely oligospermic patient from the Reproductive Center of the First Affiliated Hospital of Ningbo University was selected as the study subject. Clinical data and examination results were collected. High-throughput sequencing and bioinformatics were used to analyze the genetic etiology. And Sanger sequencing was employed to validate findings in the family. Transmission electron microscopy (TEM) was used to observe the sperm ultrastructure, and immunofluorescence analysis was performed to examine the localization of FSIP2 protein in the sperm.
RESULTS:
The patient presented with severe oligospermia, and sperm morphology displayed MMAF. TEM revealed fibrous sheath and 9+2 microtubule structural disruptions in the sperm. Sequencing identified compound heterozygous variants in the FSIP2 gene (c.17798C > T, c.5927T > G), inherited from the father and mother, respectively. According to the guidelines of the American College of Medical Genetics and Genomics, the variants were classified as pathogenic. The patient's spouse underwent intracytoplasmic single sperm injection, resulting in one embryo, but no clinical pregnancy occurred after embryo transfer.
CONCLUSION
This study reported the mutation of FSIP2 gene c.17798C > T, c.5927T > G in a patient with MMAF. These findings expand the mutational spectrum of the FSIP2 gene and provide insights for genetic and assisted reproductive counseling for patients with MMAF.
Humans
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Male
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Sperm Tail/pathology*
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Heterozygote
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Oligospermia/genetics*
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Spermatozoa
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Mutation
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Infertility, Male/genetics*
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Adult
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Pedigree
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Retrospective Studies
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Sperm Injections, Intracytoplasmic
8.Predictive value of bpMRI for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L.
Lai DONG ; Rong-Jie SHI ; Jin-Wei SHANG ; Zhi-Yi SHEN ; Kai-Yu ZHANG ; Cheng-Long ZHANG ; Bin YANG ; Tian-Bao HUANG ; Ya-Min WANG ; Rui-Zhe ZHAO ; Wei XIA ; Shang-Qian WANG ; Gong CHENG ; Li-Xin HUA
National Journal of Andrology 2025;31(5):426-431
Objective: The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods: The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results: Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62-24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16-17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12-3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion: For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans
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Male
;
Prostatic Neoplasms/diagnostic imaging*
;
Lymphatic Metastasis
;
Retrospective Studies
;
Nomograms
;
Prostate-Specific Antigen/blood*
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Lymph Nodes/pathology*
;
Pelvis
;
Predictive Value of Tests
;
Prostatectomy
;
Lymph Node Excision
;
Risk Factors
;
Magnetic Resonance Imaging
;
Logistic Models
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Middle Aged
;
Aged
9.Plastrum Testudinis Stimulates Bone Formation through Wnt/β-catenin Signaling Pathway Regulated by miR-214.
Qing LIN ; Bi-Yi ZHAO ; Xiao-Yun LI ; Wei-Peng SUN ; Hong-Hao HUANG ; Yu-Mei YANG ; Hao-Yu WANG ; Xiao-Feng ZHU ; Li YANG ; Rong-Hua ZHANG
Chinese journal of integrative medicine 2025;31(8):707-716
OBJECTIVE:
To investigate the Wnt signaling pathway and miRNAs mechanism of extracts of Plastrum Testudinis (PT) in the treatment of osteoporosis (OP).
METHODS:
Thirty female Sprague Dawley rats were randomly divided into 5 groups by random number table method, including sham group, ovariectomized group (OVX), ovariectomized groups treated with high-, medium-, and low-dose PT (160, 80, 40 mg/kg per day, respectively), with 6 rats in each group. Except for the sham group, the other rats underwent bilateral ovariectomy to simulate OP and received PT by oral gavage for 10 consecutive weeks. After treatment, bone mineral density was measured by dual-energy X-ray absorptiometry; bone microstructure was analyzed by micro-computed tomography and hematoxylin and eosin staining; and the expressions of osteogenic differentiation-related factors were detected by immunochemistry, Western blot, and quantitative polymerase chain reaction. In addition, Dickkopf-1 (Dkk-1) was used to inhibit the Wnt signaling pathway in bone marrow mesenchymal stem cells (BMSCs) and miRNA overexpression was used to evaluate the effect of miR-214 on the osteogenic differentiation of BMSCs. Subsequently, PT extract was used to rescue the effects of Dkk-1 and miR-214, and its impacts on the osteogenic differentiation-related factors of BMSCs were evaluated.
RESULTS:
PT-M and PT-L significantly reduced the weight gain in OVX rats (P<0.05). PT also regulated the bone mass and bone microarchitecture of the femur in OVX rats, and increased the expressions of bone formation-related factors including alkaline phosphatase, bone morphogenetic protein type 2, collagen type I alpha 1, and runt-related transcription factor 2 when compared with the OVX group (P<0.05 or P<0.01). Meanwhile, different doses of PT significantly rescued the inhibition of Wnt signaling pathway-related factors in OVX rats, and increased the mRNA or protein expressions of Wnt3a, β-catenin, glycogen synthase kinase-3β, and low-density lipoprotein receptor-related protein 5 (P<0.05 or P<0.01). PT stimulated the osteogenic differentiation of BMSCs inhibited by Dkk-1 and activated the Wnt signaling pathway. In addition, the expression of miR-214 was decreased in OVX rats (P<0.01), and it was negatively correlated with the osteogenic differentiation of BMSCs (P<0.01). MiR-214 mimic inhibited Wnt signaling pathway in BMSCs (P<0.05 or P<0.01). Conversely, PT effectively counteracted the effect of miR-214 mimic, thereby activating the Wnt signaling pathway and stimulating osteogenic differentiation in BMSCs (P<0.05 or P<0.01).
CONCLUSION
PT stimulates bone formation in OVX rats through β-catenin-mediated Wnt signaling pathway, which may be related to inhibiting miR-214 in BMSCs.
Animals
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MicroRNAs/genetics*
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Female
;
Rats, Sprague-Dawley
;
Wnt Signaling Pathway/genetics*
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Osteogenesis/genetics*
;
Mesenchymal Stem Cells/cytology*
;
Cell Differentiation/drug effects*
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Bone Density/drug effects*
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Ovariectomy
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Osteoporosis/drug therapy*
;
beta Catenin/metabolism*
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Rats
;
Intercellular Signaling Peptides and Proteins/metabolism*
;
Drugs, Chinese Herbal/pharmacology*
10.Psychological stress-activated NR3C1/NUPR1 axis promotes ovarian tumor metastasis.
Bin LIU ; Wen-Zhe DENG ; Wen-Hua HU ; Rong-Xi LU ; Qing-Yu ZHANG ; Chen-Feng GAO ; Xiao-Jie HUANG ; Wei-Guo LIAO ; Jin GAO ; Yang LIU ; Hiroshi KURIHARA ; Yi-Fang LI ; Xu-Hui ZHANG ; Yan-Ping WU ; Lei LIANG ; Rong-Rong HE
Acta Pharmaceutica Sinica B 2025;15(6):3149-3162
Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

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