1.Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation
Meng SHA ; Jun WANG ; Jie CAO ; Zhi-Hui ZOU ; Xiao-ye QU ; Zhi-feng XI ; Chuan SHEN ; Ying TONG ; Jian-jun ZHANG ; Seogsong JEONG ; Qiang XIA
Clinical and Molecular Hepatology 2025;31(Suppl):S285-S300
Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.
2.Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation
Meng SHA ; Jun WANG ; Jie CAO ; Zhi-Hui ZOU ; Xiao-ye QU ; Zhi-feng XI ; Chuan SHEN ; Ying TONG ; Jian-jun ZHANG ; Seogsong JEONG ; Qiang XIA
Clinical and Molecular Hepatology 2025;31(Suppl):S285-S300
Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.
3.Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation
Meng SHA ; Jun WANG ; Jie CAO ; Zhi-Hui ZOU ; Xiao-ye QU ; Zhi-feng XI ; Chuan SHEN ; Ying TONG ; Jian-jun ZHANG ; Seogsong JEONG ; Qiang XIA
Clinical and Molecular Hepatology 2025;31(Suppl):S285-S300
Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.
4.Study on the relationship between multidisciplinary teamwork behavior and organizational factors in tertiary public hospitals in Hangzhou:Based on moderated mediation model
Qiang LI ; Cong WANG ; Jian-Feng LIANG
Chinese Journal of Health Policy 2024;17(2):45-52
Objective:Analyze the impact of organizational factors on multidisciplinary teamwork behavior in tertiary public hospitals in Hangzhou,as well as the role mechanism of team atmosphere and team leadership.Provide suggestions for fully mobilizing their teamwork enthusiasm and improving teamwork efficiency.Methods:From January 2022 to March 2022,a questionnaire survey was conducted on multidisciplinary team members in tertiary public hospitals in Hangzhou using purposive sampling,and a total of 452 valid questionnaires were collected;Use the Process plugin in SPSS 26.0 software to test the moderated mediation model.Results:Positive organizational factors have a positive promoting impact on multidisciplinary teamwork behavior(β = 0.128,P<0.001),team atmosphere plays a mediating role between organizational factors and multidisciplinary teamwork behavior(β =0.063,P<0.001),and team leadership plays a negative moderating role between organizational factors and team atmosphere(β =-0.011,P<0.001).Conclusions:The behavior of multidisciplinary teamwork is influenced by multiple factors such as organizational factors,team atmosphere,and team leadership.Therefore,the hospital should actively explore a long-term operation mechanism for multidisciplinary teamwork that conforms to the characteristics of the hospital,improve top-level design,strengthen organizational investment,create a harmonious cooperation atmosphere within the team,enhance team cohesion,use shared leadership for team decision-making,and grant team members sufficient autonomy and decision-making power.
5.Research progress on endogenous small-molecule phenolics and the proposal of "phenolomics"
Hong-qian KUI ; Chuan-xin LIU ; Qiang WANG ; Hai-feng ZHAI ; Jian-mei HUANG
Acta Pharmaceutica Sinica 2024;59(2):336-349
Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.
6.DNA Polymerase θ: a Multifunctional and Error-prone DNA End Repair Enzyme
Yao WANG ; Guo-Jiang CHEN ; Jian-Nan FENG ; Yan-Chun SHI ; Jing WANG ; Yuan-Qiang ZHENG
Progress in Biochemistry and Biophysics 2024;51(3):493-503
DNA polymerase theta (Polθ), also known as DNA polymerase θ, is the member of the DNA polymerase A family and plays a crucial role in the repair of DNA double-strand breaks (DSB). Polθ has 3 distinct structural domains: the N-terminal helicase-like domain with a conserved sequence, the C-terminal polymerase domain, and the central domain, which is a disordered sequence connecting these two regions. Notably, Polθ is the only known polymerase in eukaryotes that possesses helicase activity. However, it is also an error-prone polymerase. When DNA DSBs occur, a specialized network consisting of at least 4 pathways, including classical-non homologous end joining (C-NHEJ), homologous recombination (HR), single-strand annealing (SSA), and alternative-end joining (Alt-EJ), is responsible for repairing DNA damage caused by DSBs. In the absence of major DNA repair pathways like HR, cells rely on Alt-EJ pathway mediated by Polθ to repair damaged DNA and maintain genomic stability. Nevertheless, due to the low fidelity of Polθ, Alt-EJ repair often leads to errors. Depletion of Polθ has shown to increases DSB formation and compromise genomic stability. Conversely, overexpression of Polθ has been associated with increases DNA damage markers and impairs cell cycle progression. As a result, the impact of Polθ on genome stability remains controversial. Furthermore, overexpression of Polθ is frequently observed in cancer and is associated with a characteristic mutational signature and poor prognosis. Depleting Polθ in an HR-deficient background has been shown to impair cell viability, suggesting a synthetic lethal (SL) relationship between Polθ and HR factors. In recent years, targeted chemotherapy drugs that inhibit tumor growth have gained significant attention. However, off-target effects and drug resistance pose challenges for clinical application, particularly with poly-ADP-ribose polymerase inhibitor (PARPi). Blocking Polθ activity in HR-deficient tumor cells has been found to reverse PARPi resistance, making Polθ a very promising therapeutic target in cancer treatment. The availability of crystal structures for both helicase and polymerase domain has facilitated the design of potent inhibitors of Polθ. Currently, several highly specific and effective small molecule inhibitors targeting Polθ, such as Novobiocin, RP-6685, and ART558, have been reported to effectively block various cancers with HR deficiency. The initial success of these inhibitors points to new directions for treating BRCA1/2-mutated tumors. Additionally, reducing the Alt-EJ repair pathway mediated by Polθ can improve HR repair efficiency and increase the chance of exogenous gene target integration (TI), suggesting potential new applications for Polθ inhibitors. This article reviews the recent research progress on the molecular function of Polθ and its involvement in the Alt-EJ pathway modification mechanism, providing insights for a deeper understanding of this field.
7.Role of Hedgehog signaling pathway in muscle bone symbiosis in osteo-sarcopenia
Yan-Dong LIU ; Qiang DENG ; Zhong-Feng LI ; Ran-Dong PENG ; Yu-Rong WANG ; Jia-Ming LI ; Ping-Yi MA ; Jian-Qiang DU
The Chinese Journal of Clinical Pharmacology 2024;40(16):2433-2437
This article elaborates on the complex cross-talk and close relationship between muscles and bones involved in this disease,as well as its pathogenesis.It also summarizes that the difficulty of its treatment lies in the need to simultaneously consider both muscles and bones.And elaborated on the key role of the Hedgehog signaling pathway in embryonic development,tissue morphology establishment,and human tissue regeneration and repair.Investigated the remodeling effect of the Hedgehog signaling pathway on skeletal muscle from three aspects:Proliferation and differentiation of muscle stem cells,precursor cell and muscle fiber generation,inhibition of inflammation,and regulation of immunity;this article elucidates the role of the Hedgehog signaling pathway in bone reconstruction from two aspects.
8.Investigation of Adductive Characteristics of Sulfur Mustards with Active Thiols
Meng-Yao ZHANG ; Jin-Long CAI ; Meng-Qiang GONG ; Bin XU ; Jian-Feng WU ; Hai-Xia WU ; Jian-Wei XIE
Chinese Journal of Analytical Chemistry 2024;52(7):995-1003,中插30-中插34
An analytical method based on ultra high performance liquid chromatography-high resolution tandem mass spectrometry(UHPLC-HRMS/MS)and high performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-TQ MS)was established to reveal the characteristics of various sulfur mustard analogs with different active thiol molecules in CWC Schedule 1.A.04.Firstly,the toxic agents were prepared by micro-directed synthesis,and then the differences of the reactivity and abundance of formed adducts between different sulfur mustards and glutathione(GSH),cysteine(Cys)and N-acetylcysteine(NAC)in incubation solution,plasma and cell were investigated,respectively.The results indicated that all target sulfur mustards could react with three kinds of thiol molecules.The content of Cys and sulfur mustard adducts in plasma was higher than that of GSH and sulfur mustard adducts,while NAC and sulfur mustard adducts might have fewer types of adducts due to low content or poor mass spectrometry response.Additionally,the content of GSH and sulfur mustard adducts in exposed cells was higher than that of Cys,which should be due to the significant difference in the content of thiol molecules in plasma and cells.
9.Multi-parametric MRI radiomics-based nomogram model for predicting the lymphovascular space invasion of endometrial endometrioid adenocarcinoma
Xiao-Liang MA ; Min-Hua SHEN ; Feng-Hua MA ; Guo-Fu ZHANG ; Jian-Jun ZHOU ; Meng-Su ZENG ; Jin-Wei QIANG
Fudan University Journal of Medical Sciences 2024;51(3):306-314,322
Objective To investigate the feasibility and value of a multi-parametric MRI radiomics-based nomogram model for pretreatment predicting the lymphovascular space invasion(LVSI)of endometrial endometrioid adenocarcinoma(EEA).Methods Preoperative MRI and baseline clinical characteristics of 205 EEA patients were prospectively collected from Oct 2020 to Jan 2022 in the Obstetrics and Gynecology Hospital,Fudan University,and randomly divided into training set(n=123)and validation set(n=82)in a 6∶4 ratio.The whole-tumor region of interest was manually drawn on T2-weighted imaging,diffusion-weighted imaging(apparent diffusion coefficient),and dynamic contrast-enhanced MRI,respectively,for radiomics features extraction.In the training set,univariate and multivariate Logistic regression analysis were used to select independent clinical predictors of LVSI(+)and construct the clinical model.The least absolute shrinkage and selection operator(LASSO)regression and multivariate Logistic regression analysis were used to select optimal radiomics features to form a radiomics signature.A combined nomogram model was established by integrating clinical independent predictors and the radiomics signature,and validated in the validation set.The predicting performance and clinical net benefit were evaluated by using the area under the receiver operating characteristic curve(AUC)and clinical decision curve analysis,respectively.Results Of the 205 EEA cases,144 cases were LVSI(-)and 61 cases were LVSI(+).Menopausal status,CA125,and CA199 were independent clinical predictors for the LVSI(+),and contributing to a clinical model with AUCs of 0.714(training)and 0.731(validation).From 8 240 extracted radiomics features,five were selected to construct a MRI radiomics signature after de-redundancy and LASSO dimensionality reduction,yielding AUCs of 0.860(training)and 0.759(validation).The combined nomogram model showed AUCs of 0.887(training)and 0.807(validation),outperforming others and achieving maximum clinical benefit in a large range of threshold probability in both training and validation sets.Conclusion The multi-parametric MRI-based nomogram model has the potential for pretreatment predicting the LVSI status of EEA,providing valuable information for clinical management decision-making and improving patient's clinical benefits.
10.Comparison of pediatric pelvic fractures and associated injuries caused by different types of road traffic accidents
Bao-Jian SONG ; Qiang WANG ; Wei FENG ; Dan-Jiang ZHU ; Xue-Jun ZHANG
Chinese Journal of Traumatology 2024;27(6):372-379
Purpose::To explore the clinical characteristics of pediatric pelvic fracturs caused by traffic accidents and to analyze the accompanying injuries and complications.Methods::A total of 222 cases involved traffic accidents was enrolled in this case-control study. The data of children with pelvic fractures caused by traffic accidents who were admitted to our hospital from January 2006 to December 2021 were analyzed retrospectively. Sex, age, Tile classification, abbreviated injury scale score, injury severity score, mortality, and accompanying injuries were studied. The ANOVA was used for measurement data, and the non-parametric rank sum test was used for non-normally distributed data. The Fisher's exact probability method was used for the count data.Results::Of all enrolled cases, 140 are boys and 82 are girls, including 144 cases aged < 6 years, 65 aged between 6 and 12 years, and 13 aged > 12 years. Depending on the injury mechanism, there are 15 cases involving pedestrians vs. motorcycles (PVM), 91 cases involving pedestrians vs. passenger cars (PVC), 78 cases involving pedestrians vs. commercial vehicles (PVV), and 38 cases involving motor vehicles vs. motor vehicles (MVM). Associated injuries are reported in 198 cases (89.2%), primarily involving the abdomen injury in 144 cases (64.9%), and lower limb injury in 99 cases (44.6%). PVV injury involves longer hospital stay ( p =0.004). Intensive care unit admission rate is significantly higher in the MVM group than in other groups ( p =0.004). Head injury ( p =0.001) and face injury ( p =0.037) are more common in the MVM group, whereas abdominal injury ( p =0.048) and lower limb injury ( p =0.037) are more common in the PVV group. In the MVM group, the brain injury ( p =0.004) and femoral neck injury ( p =0.044) are more common. In the PVM group, the mediastinum ( p =0.004), ear ( p =0.009), lumbar vertebrae ( p =0.008), and spinal cord ( p =0.011) are the most vulnerable regions, while in the PVV group, the perineum ( p < 0.001), urethra ( p =0.001), rectum ( p =0.006), anus ( p =0.004), and lower limb soft tissues ( p =0.024) are the most vulnerable regions. Children aged > 12 years have higher pelvic abbreviated injury scale scores ( p =0.019). There are significant differences in the classification of pelvic fractures among children < 6, 6 -12, and > 12 years of age, with Tile C being more likely to occur in children > 12 years of age ( p =0.033). Children aged > 12 years are more likely to sustain injuries to the spleen ( p =0.022), kidneys ( p =0.019), pancreas ( p < 0.001), lumbar vertebrae ( p =0.013), and sacrum ( p =0.024). The MVM group has the highest complication rate ( p =0.003). Conclusion::PVC is the leading cause of the abdomen and lower extremities injury and has the most concomitant injuries. Different traffic injuries often lead to different associated injuries. Older children are more likely to sustain more severe pelvic fractures and peripelvic organs injuries. The MVM group has the highest extent of injury and complication rates.

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