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.

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.

Objective:To construct a prediction model for the prognosis of breast cancer patients with long non-coding RNA expression characteristics.Methods:To construct a long non-coding RNA(LncRNA) model for predicting the prognosis of breast cancer patients.Methods Analyzing LncRNA expression profiles and clinical characteristics of 1 081 breast cancer patients in the cancer genome atlas (TCGA) database.Performing differential expression analysis and univariate analysis on 112 paired breast cancer and normal breast tissues′ transcriptome sequencing data in the TCGA database, and screened for differentially expressed (DELncRNAs) that significantly correlated with the prognosis of BRCA (To reduce batch effects, sequencing data has been normalized using the DESeq function). One thousand eighty-one breast cancer patients were randomly divided into two groups: training set (541) and validation set (540). Performing Cox proportional hazard regression using DELncRNAs and establishing a multi-LncRNA prognosis model in the training set, followed by proportional hazards assumption test(PH assumption test). Patients were divided into high-risk and low-risk groups based on calculated risk score.Kaplan-Meier method was used for survival analysis, and 540 patients′ data were used for validation.To evaluate the prognostic value of the model in patients with squamous cell carcinoma of the lung and hepatocarcinoma in TCGA database.Gene Set Enrichment Analysis (GSEA) was used to analyze the specific mechanism of lncrna affecting the survival of patients.Results:There were 2815 differentially expressed genes screened by transcriptome sequencing, 91 of which were significantly related to the prognosis of breast cancer patients ( P<0.05). Based on the Cox regression analysis of 91 delncrna expression data from 541 breast cancer patients in training set, a Cox proportional risk regression model was constructed based on 5 LncRNA (training set AUC=0.746, validation set AUC=0.650): AC004551.1, MTOR-AS1, KCNAB1-AS2, FAM230G and LINC01283, and PH assumption test( P=0.388). K-M survival analysis showed that the survival time of high-risk group was significantly worse than that of low-risk group (median survival time: 7.049 and 12.21 years, HR 0.367, 95% CI0.228-0.597, P<0.001), and the survival time of high-risk group was significantly shorter than that of low-risk group (median survival time: 7.57 and 10.85 years, HR 0.412, 95% CI0.214-0.793, P<0.001). Similar prediction results were also obtained in other cancer species of TCGA: lung squamous cell carcinoma ( HR 0.604, 95% CI0.383-0.951, P=0.007) and liver cell carcinoma ( HR 0.551, 95% CI0.307-0.987, P=0.011). GSEA results suggested that the expression patterns of the above five LncRNA were related to the cell cycle regulation of tumor cells. Conclusion:The prognostic model constructed based on expression profile of AC004551.1, MTOR-AS1, KCNAB1-AS2, FAM230G and LINC01283 can be used to predict the prognosis of breast cancer patients, which is helpful to further guide clinical treatment.

Objective:To evaluate the biomechanical performance of our self-designed anatomical plate for posterolateral tibial plateau in comparison with conventional plates for treatment of posterolateral tibial plateau fractures.Methods:A novel anatomic plate for posterolateral tibial plateau was designed according to the data measured in the superior fibular capitulum and 3D CT segmentation. Twenty-four knee joints were obtained from 12 freshly frozen adult cadavers to make models of posterolateral tibial plateau fracture. The models were divided into 3 groups( n=8). In group A, fixation was simulated via the supra-fibular-head approach after autogenous iliac bone-graft by our self-designed anatomic plate for posterolateral tibial plateau; in group B, fixation was simulated via the posterior tibial approach after autogenous iliac bone-graft by a small T-plate; in group C, fixation was simulated via the supra-fibular-head approach after autogenous iliac bone-graft by a normal L-plate. Biomechanical tests were carried out in the 3 groups to measure the vertical displacements of split bone fragment under the vertical compression loads of 500 N, 1,000 N and 1,500 N and the maximum compression upon failure of internal fixation (compressed displacemen t=3 mm). Results:At the vertical compression loads of 500 N, 1,000 N and 1,500 N, the vertical displacements of split bone fragment showed significant differences among the 3 groups ( P<0.05); there was a significant difference between group C and groups A and B, respectively ( P<0.05), but an insignificant difference between group A and group B ( P>0.05) though group A performed slightly better. In terms of the maximum compression upon failure of internal fixation, significant differences existed among the 3 groups ( P<0.05); there was a significant difference between group C and groups A and B, respectively ( P< 0.05), but an insignificant difference between group A and group B ( P>0.05). Conclusions:Our self-designed anatomic plate for posterolateral tibial plateau can firmly fixate the fracture fragments of posterolateral condyle.

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.

Objective:To analyze the viral nucleic acid and cytokines in 12 children with 2019-nCoV infection.Methods:Clinical and laboratory data of the children diagnosed with 2019-nCoV infection in Guangzhou Women and Children′s Medical Center from January to April 2020 were retrospectively analyzed. Throat and anal swabs were collected on alternate days for the detection of 2019-nCoV nucleic acid by fluorescence quantitative PCR. Flow cytometry was used to detect serum cytokines including IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL-22, TNF-α and TNF-β during the early (both throat and anal swab tests were positive), the intermediate (throat swab test was negative, while anal swab test remained positive), and the convalescence (both throat and anal swab tests were negative) stages of infection.Results:A total of 12 children were enrolled in this study. The male-to-female ratio was 5∶1. The average age was (7.0±4.3) years. There were two asymptomatic, five mild and five common cases. No severe or critical cases were involved. Initially, throat and anal swab nucleic acid tests were simultaneously positive in nine children newly diagnosed in our hospital and the median time of viral shedding in throat swab was longer than that in throat swab [32 (4.5, 45.0) d vs 3 (2, 9) d, Z=11.0, P=0.010]. The median difference of viral shedding time between anal swab and pharyngeal swab was 25.5 (1.5, 42.8) d. The overall levels of serum cytokines IL-17A, IL -4 and IL-5 in different stages of the disease (early, intermediate and convalescence stage) were statistically different ( Z or F, P values were 8.33, 0.016; 5.36, 0.010 and 6.56, 0.004, respectively), and a significant increase was observed in the intermediate stage of infection. IL-17F, IL-2 and IL-22 were all increased during the infection, but there was no significant statistical difference among the three stages ( P>0.05). Conclusions:It was noted that intestinal viral shedding needed a longer time. Although the infectivity has not been determined, higher requirements have been put forward for disease prevention and control. Cytokines secreted by Th2 and Th17 cells were involved in the immune response in children with non-severe 2019-nCoV infection. Monitoring viral shedding and cytokine changes in pediatric patients would be conducive to disease assessment.

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 get a knowledge of the current status of organ donation and utilization after citizen's death in Wuxi District, and thereby provide ideas and basis for further development of organ donation work in local areas. Methods Clinical data from 151 organ donors, included 37 successful donors and 114 potential donors, were retrospectively analyzed. The reasons for donation failure of potential donors were analyzed. The general information for successful donors was collected. And the information on organ donation and organ utilization in successful donors were analyzed. Results Among the 151 organ donors, 37 were successful donors, with the conversion rate reaching 24.5%. For the 114 donors with failed organ donation, the reasons for failure included family disagreement, failure to meet donation status criteria, insufficient evaluation time, and unresolved work injury disputes. The categories for organ donation included 34 cases of donation after brain death followed by cardiac death (DBCD), 3 cases of donation after brain death (DBD), and no case of donation after cardiac death (DCD). The reasons for death of donors includes 19 cases of craniocerebral trauma, 14 cases of stroke and 4 cases of others. Among the 37 cases of successful donors, the majority were floating population. A total of 154 major organs and tissues were donated, of which 124 were major organs. The number of major organs and tissues donated per citizen was (4.2± 1.6) and the number of major organs donated per citizen was (3.4± 1.1). The utilization rate of the 154 donated organs reached 96.7% (149/154), with Nanjing, Wuxi, Suzhou and Changzhou ranking the top 4 of organ distribution. Conclusions The rate for successful organ donation and conversion after citizen's death is low in Wuxi District. The organ donation work networks in local areas should be established. And organ donation promotion efforts and skills training for coordinators should be developed.

OBJECTIVE: To explore the clinical and laboratory characteristics of 5 patients with myeloid leukemia and t(12;22)(p13;q12). METHODS: Bone marrow cells were cultured for 24 h and analyzed by standard R-banding. Rearrangement of the MN1 gene was detected by fluorescence in situ hybridization (FISH) using dual color break-apart MN1 probes. MN1-ETV6 and ETV6-MN1 fusion genes were detected by reverse transcription polymerase chain reaction (RT-PCR). And the products were subjected to direct sequencing. RESULTS: Among the 5 patients, 2 had AML-M0, 2 had AML-M4, and 1 had CMML at the initial diagnosis. t(12;22)(p13;q12) was the primary abnormality among all patients. Rearrangements of MN1 gene were detected by FISH in all patients. MN1-ETV6 and ETV6-MN1 fusion genes were detected respectively in 4 and 3 patients. CONCLUSION t(12;22)(p13;q12) is a rare but recurrent chromosomal abnormality in myeloid leukemia, and is related to poor prognosis. allo-SCT is valuable for patients with t(12;22)(p13;q12).
Chromosome Banding ; Chromosomes, Human, Pair 12 ; Chromosomes, Human, Pair 22 ; Cytogenetics ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myeloid ; genetics ; Oncogene Proteins, Fusion ; Translocation, Genetic