Acute liver failure (ALF) is lack of broadly approved therapeutic strategy except liver transplantation. As a glycogen metabolic intermediate, UDP-glucose (UDP-G) has been considered to accelerate liver repairment. Nevertheless, the role of UDP-G and its receptor P2Y purinoceptor 14 (P2Y₁₄R) in ALF remains unknown. The present study aims to investigate the role and underlying mechanisms of UDP-G/P2Y₁₄R axis in ALF. In this study, hepatic P2Y₁₄R is significantly increased in TAA-induced and partial hepatectomy-induced ALF, while knockout of whole-body P2Y₁₄R aggravates liver failure, manifested by inhibiting β-Catenin-mediated liver regeneration. Consistently, P2Y₁₄R deficiency exhibits impaired liver regeneration in mice suffer partial hepatectomy. Importantly, only hepatocellular specific deletion of P2Y₁₄R (P2Y₁₄R ^flox/flox Alb ^cre/+ ) mice shows a similar phenomenon, rather than stellate cell specific deletion of P2Y₁₄R (P2Y₁₄R ^flox/flox Lrat ^cre/+ ) mice. Mechanistically, P2Y₁₄R induction regulates methylation of Dact-2 through CREB/DNMT3b signals in hepatocytes, subsequently inhibiting the expression of Dact-2 which is a stabilizer of β-Catenin degradation complex, leading to the activation of β-Catenin -mediated liver regeneration. Interestingly, the administration of exogenous UDP-G can accelerate liver regeneration and liver function recovery after partial hepatectomy in hepatocellular carcinoma mice. Together, the findings propose an unrecognized role of P2Y₁₄R in ALF and provide an effective adjuvant strategy for treatment of ALF.

Objective:To investigate the prognostic value of 18F-FDG PET/CT-based habitat radiomics combined with stacking ensemble learning model in overall survival (OS) of patients with hepatocellular carcinoma (HCC). Methods:A total of 136 HCC patients (114 males, 22 females, age (55.3±10.4) years) who underwent 18F-FDG PET/CT before treatment between January 2018 and January 2023 were retrospectively analyzed. Eighty-five cases from Tianjin First Central Hospital and 51 cases from Tianjin Medical University Cancer Institute and Hospital were used as a training cohort and an external validation cohort, respectively. The tumor volume of interest (VOI) was delineated on PET and CT images, and a total of 4 habitats were segmented by using the Otsu algorithm, including PET high ∩ CT low, PET low ∩ CT low, PET high ∩ CT high, and PET low ∩ CT high. After the feature selection, a total of 36 stacking ensemble learning models were established, and the optimal model was selected based on the calculated concordance index (C-index). Moreover, a combined model was developed by integrating the optimal model with clinical information. The predictive efficacy of those models was assessed by time-dependent ROC curves. Results:The model based on PET high ∩ CT high habitat radiomics features with multilayer perceptron (MLP) classifier had the highest C-index (0.770) in the external validation cohort, and it was regarded as the optimal radiomics model. The combined model incorporating this model with clinical information achieved an improved C-index of 0.815 in the external validation cohort. The combined model outperformed the other models for OS prediction, with a time-dependent AUC of 0.919, 0.900, and 0.862 in predicting the 1-year, 2-year, and 3-year OS, respectively. Conclusions:18F-FDG PET/CT-based habitat analysis outperforms traditional radiomics in OS prediction for HCC patients. By integrating the optimal habitat model with the clinical model, the combined model is able to improve the predictive efficacy.

Objective To predict the current and future ecological suitability distribution areas of Scutellariae Radix in Shandong Province at present and in the future;To screen the main environmental factors affecting its suitable distribution;To provide a reference for the protection of wild resources and the site selection artificial planting of Scutellariae Radix.Methods Taking Scutellariae Radix as the research object,based on the MaxEnt model,the potential suitable habitats were predicted using 84 distribution points of and 48 environmental factors of Scutellariae Radix,and the main environmental factors affecting the distribution of Scutellariae Radix were explored.Its potential suitable habitat areas were predicted under four greenhouse gas emission concentration scenarios(SSP126,SSP245,SSP370,and SSP585)for the years 2021-2040,2041-2060,2061-2080 and 2081-2100.Results The MaxEnt model was optimized through feature combination and regularization constant parameters,and its predictive ability was good(AUC value of 0.871).The primary driving environmental factors affecting its distribution were the maximum temperature in the warmest month(bio_05),soil gravel content(cf05)and altitude(elev).Under the current climate conditions,Scutellariae Radix is mainly distributed in the hilly areas of central and southern Shandong and some areas of in the hilly areas of Jiaodong.Under the future climate conditions of SSP126,SSP245,SSP370 and SSP585,the areas of suitable habitat of Scutellariae Radix in Shandong will show a decreasing trend.Except for the SSP126,the medium and high adaptation areas of Scutellariae Radix will disappear in the other three modes.Conclusion The results of this study can provide an important reference for the protection,rational utilization and planting layout of Scutellariae Radix in Shandong Province.

Objective To predict the current and future ecological suitability distribution areas of Scutellariae Radix in Shandong Province at present and in the future;To screen the main environmental factors affecting its suitable distribution;To provide a reference for the protection of wild resources and the site selection artificial planting of Scutellariae Radix.Methods Taking Scutellariae Radix as the research object,based on the MaxEnt model,the potential suitable habitats were predicted using 84 distribution points of and 48 environmental factors of Scutellariae Radix,and the main environmental factors affecting the distribution of Scutellariae Radix were explored.Its potential suitable habitat areas were predicted under four greenhouse gas emission concentration scenarios(SSP126,SSP245,SSP370,and SSP585)for the years 2021-2040,2041-2060,2061-2080 and 2081-2100.Results The MaxEnt model was optimized through feature combination and regularization constant parameters,and its predictive ability was good(AUC value of 0.871).The primary driving environmental factors affecting its distribution were the maximum temperature in the warmest month(bio_05),soil gravel content(cf05)and altitude(elev).Under the current climate conditions,Scutellariae Radix is mainly distributed in the hilly areas of central and southern Shandong and some areas of in the hilly areas of Jiaodong.Under the future climate conditions of SSP126,SSP245,SSP370 and SSP585,the areas of suitable habitat of Scutellariae Radix in Shandong will show a decreasing trend.Except for the SSP126,the medium and high adaptation areas of Scutellariae Radix will disappear in the other three modes.Conclusion The results of this study can provide an important reference for the protection,rational utilization and planting layout of Scutellariae Radix in Shandong Province.

Objective:To investigate the prognostic value of 18F-FDG PET/CT-based habitat radiomics combined with stacking ensemble learning model in overall survival (OS) of patients with hepatocellular carcinoma (HCC). Methods:A total of 136 HCC patients (114 males, 22 females, age (55.3±10.4) years) who underwent 18F-FDG PET/CT before treatment between January 2018 and January 2023 were retrospectively analyzed. Eighty-five cases from Tianjin First Central Hospital and 51 cases from Tianjin Medical University Cancer Institute and Hospital were used as a training cohort and an external validation cohort, respectively. The tumor volume of interest (VOI) was delineated on PET and CT images, and a total of 4 habitats were segmented by using the Otsu algorithm, including PET high ∩ CT low, PET low ∩ CT low, PET high ∩ CT high, and PET low ∩ CT high. After the feature selection, a total of 36 stacking ensemble learning models were established, and the optimal model was selected based on the calculated concordance index (C-index). Moreover, a combined model was developed by integrating the optimal model with clinical information. The predictive efficacy of those models was assessed by time-dependent ROC curves. Results:The model based on PET high ∩ CT high habitat radiomics features with multilayer perceptron (MLP) classifier had the highest C-index (0.770) in the external validation cohort, and it was regarded as the optimal radiomics model. The combined model incorporating this model with clinical information achieved an improved C-index of 0.815 in the external validation cohort. The combined model outperformed the other models for OS prediction, with a time-dependent AUC of 0.919, 0.900, and 0.862 in predicting the 1-year, 2-year, and 3-year OS, respectively. Conclusions:18F-FDG PET/CT-based habitat analysis outperforms traditional radiomics in OS prediction for HCC patients. By integrating the optimal habitat model with the clinical model, the combined model is able to improve the predictive efficacy.

Objective: To evaluate the mutation rates of homologous recombination repair (HRR) genes and the impact of these mutations on the clinical characteristics of metastatic endometrial cancer (EC). Methods: Somatic DNA from 895 patients with metastatic EC in the Memorial Sloan Kettering-Metastatic Events and Tropisms cohort was assessed for mutations in 10 HRR genes (BRCA1, BRCA2, ATM, BARD1, BRIP1, PALB2, RAD51C, RAD51D, CHEK2, and CDK12).The correlation between the mutation status of HRR genes and the clinical characteristics of patients with metastatic EC was evaluated. Results: Somatic mutations in HRR genes were detected in 106 (11.8%) patients with metastatic EC. Compared with nonmutation carriers, a greater proportion of carriers had endometrioid carcinoma (76.4% vs. 50.3%, p<0.001). Regarding the TCGA classification, the proportions of the POLE-ultramutated (POLEmut) and mismatch repair-deficient (dMMR) subtypes were significantly greater among mutation carriers than noncarriers (20.8% vs.0.4%, p<0.001; 34.9% vs. 11.9%, p<0.001, respectively). The carriers had a significantly lower frequency of TP53 mutations than noncarriers (25.5% vs. 54.1%, p<0.001). Fewer mutation carriers than noncarriers had intra-abdominal and lung metastases (41.5% vs.54.2%, p=0.014; 19.8% vs. 30.3%, p=0.026, respectively). The mutation status of HRR genes did not significantly affect the overall survival of patients with metastatic EC. Conclusion Somatic HRR mutations are detected in 11.8% of metastatic EC. Compared with noncarriers, HRR mutation carriers in metastatic EC have higher proportions of endometrioid carcinoma, POLEmut, and dMMR subtypes, and unique metastatic patterns.However, the prognoses are similar regardless of HRR status.

The declining fertility has emerged as a significant concern impacting national welfare, with obesity identified as a major contributing factor. In the hypothalamus, gonadotropin-releasing hormone(GnRH) neurons release GnRH, which regulates the secretion of estrogen and testosterone via the hypothalamic-pituitary-gonadal(HPG) axis, thereby influencing sexual development and fertility. The proper function of GnRH neurons is crucial for maintaining normal sexual development and fertility. Research indicates that obesity can impact GnRH neuron function through several pathways, such as disrupting pulsatile secretion core kisspeptin neurons, causing imbalance in energy sensing and metabolic factor secretion, and triggering hypothalamic inflammation. These pathways directly or indirectly influence GnRH neuron function in the hypothalamus, which ultimately affects sexual development and impairs fertility. Therefore, this review consolidates recent advancements in understanding the mechanisms by which obesity induces dysfunction in hypothalamic GnRH neurons, offering new perspectives for early clinical interventions aimed at enhancing fertility outcomes in obese individuals.

In recent years, organ donation has developed rapidly in China, whereas the brain death criteria have not been confirmed by relevant legislation. In this article, the current legislation situation of brain death criteria at home and abroad, and the current criteria for determination of death for organ donation after citizen's death in China were introduced. The necessity of legislation of brain death criteria in China was discussed from the perspective of organ donation, and suggestions on the form and content of brain death criteria legislation were proposed based on the actual national conditions, aiming to provide reference for the legislation of brain death criteria.

Objective To explore the key initiatives and effective methods for preparing the constructions of emergency-oriented hospitals under COVID-19 pandemic. Methods The wartime mechanism was strengthened by adhering to unified leadership, trengthening the top-level design and clarifying the division of responsibilities. Objective management was used as a means to take into account the key of personnel allocation and training, prevention and control of hospital infection, transformation of contagious ward, logistic support, equipment and material supply and construction of system and process. Results The preparations and constructions of the emergency-oriented hospitals were completed in 72 hours，which passed the acceptance and inspections from infection control experts，who appraised our work to be “the highest in difficulty, the fastest in project progress and the highest in quality". Totally, upon to the preparations，14 medical teams were set up and the layout process reestablishment of 14 wards was completed, the installation and preparation of nearly 10000 sets/pieces of medical equipment and medical materials were completed as well and more than 80 work systems and process systems for 9 major modules were established. Conclusion The preparations and constructions of emergency-oriented hospitals should be performed upon the thorough implementation of the decisions and arrangements by the municipal Party committee and the municipal government, insisting on the wartime thinking and establishment of high-quality management team and effective goal management focusing on details and actual needs of medical staff.

Objective: To study the value of unmethylated cytosine guanine dinucleotide oligodeoxynucleotide (DSP30) and IL-2 in the conventional cytogenetic (CA) detection of the chromosomal aberrations in chronic lymphocytic leukemia (CLL) . Methods: Bone marrow or peripheral blood cells of CLL patients were cultured with DSP30 plus IL-2 for 72 h, following which R-banding analysis was conducted. Fluorescence in situ hybridization (FISH) was performed in 85 patients. CA results were compared with data obtained by FISH. Results: Among 89 CLL patients, the success rate of chromosome analysis was 94.38% (84/89) . Clonal aberrations were detected in 51 patients (51/84, 60.71%) . Of them, 27 (27/51, 52.94%) were complex karyotype. Among 85 CLL patients tested by FISH, chromosomal abnormalities were detected in 74 (74/85, 87.06%) patients, of which 2 (2/74) patients were complex karyotypes, accounting for 2.70%. Of the 85 CLL patients examined by FISH, 50 had abnormal karyotype analysis, 30 had normal karyotype, 5 failed to have chromosome analysis. Among them, 25 cases showed clonal aberrations by FISH assay but normal by CA, and 4 cases were normal by FISH but displayed aberrations in chromosome analysis, and totally 78 (91.76%) cases with abnormality detected by the combination of the two methods. The frequency of 13q- abnormality detected by FISH was significantly higher than that by CA analysis (69.41%vs 16.67%, P<0.001) , while the frequency of 11q-,+12 and 17p- detected by two methods showed no significant difference (P>0.05) . The detection rate of complex abnormalities in conventional karyotype analysis was higher than that in FISH (50.98%vs 2.70%) . In addition, 11 low-risk and 9 intermediate-risk patients according to FISH results showed complex karyotype by cytogenetics, and were classified into high-risk cytogenetic subgroup. Conclusion DSP30 and IL-2 are effective in improving the detection rate of CA in CLL patients (60.71%) and CA is more effective to detect complex karyotype. However, FISH had a higher overall abnormality detection rate (87.06%) than CA, especially for 13q-. The combination of CA and FISH not only enhanced the detection rate of clonal aberrations to 91.76%, but also provided more precise prognosis stratification for CLL patients, thus to provide more information for clinical implication.