ObjectiveTo establish a new noninvasive， simple， and convenient clinical predictive model by identifying independent predictive factors for rebleeding after endoscopic therapy in cirrhotic patients with esophagogastric variceal bleeding （EGVB）， and to provide a basis for individualized risk assessment and development of clinical intervention strategies. MethodsCirrhotic patients with EGVB who were diagnosed and treated in The First Affiliated Hospital of Xi’an Medical University from September 2018 to October 2023 were enrolled as subjects， and according to whether the patient experienced rebleeding within 1 year after endoscopic therapy， they were divided into rebleeding group with 93 patients and non-rebleeding group with 84 patients. Clinical data were collected and analyzed. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. A Logistic model was established based on the results of the univariate and multivariate analyses， and the receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to assess the accuracy of the model. R software was used to visualize the model by plotting a nomogram， and the Bootstrap method was used for internal validation of the model. ResultsThe multivariate analysis showed that red blood cell count （RBC）， cholinesterase （ChE）， alkaline phosphatase （ALP）， albumin （Alb）， thrombin time （TT）， portal vein trunk diameter， sequential therapy， and primary prevention were independent predictive factors for rebleeding. Based on the results of the multivariate analysis， a logistic model was established as logit（P）=-0.805-1.978×（RBC）+0.001×（ChE）-0.020×（ALP）-0.314×（Alb）+0.567×（TT）+0.428×（portal vein trunk diameter）-2.303×［sequential therapy （yes=1， no=0）］-2.368×［primary prevention （yes=1， no=0）］. The logistic model （AUC=0.928， 95% confidence interval ［CI］： 0.893—0.964， P<0.001） had a better performance in predicting rebleeding than MELD score （AUC=0.603， 95%CI： 0.520—0.687， P=0.003）， Child-Pugh class （AUC=0.650， 95%CI： 0.578—0.722， P=0.001）， and FIB-4 index （AUC=0.587， 95%CI： 0.503—0.671， P=0.045）. The model had an optimal cut-off value of 0.607， a sensitivity of 0.817， and a specificity of 0.817. Internal validation confirmed that the model had good predictive performance and accuracy. ConclusionSequential therapy， implementation of primary prevention， an increase in RBC， and an increase in Alb are protective factors against rebleeding， while prolonged TT and widened main portal vein diameter are risk factors. The logistic model based on these independent predictive factors can predict rebleeding and thus holds promise for clinical application.

Human papilloma virus (HPV), a cancer-causing DNA virus, is a most common sexually transmitted virus and one of the major public health problems worldwide currently. Although HPV infection is relatively common in men, routine HPV detection is still difficult to be applied in clinical practice due to the lack of standard HPV detection methods and the complexity of its detection. Recent studies have explored the relationship between HPV and genitourinary tumors, revealed different results because of geographic differences, histological subtypes and detection methods, and stressed the importance of clarifying the role of HPV in the development and progression of genitourinary tumors. This review focuses on the complicated relationship of HPV with male genitourinary tumors, reveals its main carcinogenic mechanisms, and presents a new insight into the impact of HPV on the genitourinary system.
Humans ; Male ; Papillomavirus Infections/virology* ; Papillomaviridae ; Urologic Neoplasms/virology*

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.

Homeostasis and energy and substance metabolism reprogramming shape various tumor microenvironment to sustain cancer stemness, self-plasticity and treatment resistance. Aiming at them, a lipid-based pharmaceutical loaded with CaO₂ and glucose oxidase (GOx) (LipoCaO₂/GOx, LCG) has been obtained to disrupt calcium homeostasis and interfere with glycometabolism. The loaded GOx can decompose glucose into H₂O₂ and gluconic acid, thus competing with anaerobic glycolysis to hamper lactic acid (LA) secretion. The obtained gluconic acid further deprives CaO₂ to produce H₂O₂ and release Ca²⁺, disrupting Ca²⁺ homeostasis, which synergizes with GOx-mediated glycometabolism interference to deplete glutathione (GSH) and yield reactive oxygen species (ROS). Systematical experiments reveal that these sequential multifaceted events unlocked by Ca²⁺ homeostasis disruption and glycometabolism interference, ROS production and LA inhibition, successfully enhance cancer immunogenic deaths of breast cancer cells, hamper regulatory T cells (Tregs) infiltration and promote CD8⁺ T recruitment, which receives a considerably-inhibited outcome against breast cancer progression. Collectively, this calcium homeostasis disruption glycometabolism interference strategy effectively combines ion interference therapy with starvation therapy to eventually evoke an effective anti-tumor immune environment, which represents in the field of biomedical research.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective:To evaluate the effect of anterior quadratus lumborum block at the lateral supra-arcuate ligament on the postoperative pulmonary function in patients undergoing robot-assisted laparoscopic radical prostatectomy under general anesthesia.Methods:Seventy-two American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients, aged 50-80 yr, with body mass index of 18.5-27.9 kg/m 2, scheduled for elective robot-assisted laparoscopic radical prostatectomy under general anesthesia, were divided into 2 groups ( n=36 each) using a random number table method: control group and observation group. After induction of general anesthesia, observation group underwent anterior quadratus lumborum block at the lateral supra-arcuate ligament under ultrasound guidance, with 20 ml of 0.375% ropivacaine administered on each side. Control group only received total intravenous anesthesia. Postoperative analgesia was provided by patient-controlled intravenous analgesia until 48 h after operation, and intravenous dezocine was administered as rescue analgesic when the visual analogue scale score at rest≥4. Pulmonary function was assessed at 1 day before surgery and 1-7 days after surgery. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1), maximal mid-expiratory flow rate (FEF 25%-75%), and time to recovery of 80% predicted pulmonary function were recorded. Arterial blood gas analysis was performed at 1 day before surgery and 1-3 days after surgery, and SpO 2, PaO 2 and PaCO 2 were recorded. The consumption of intraoperative remifentanil, effective pressing times of patient-controlled analgesia, and the number of patients required rescue analgesia were recorded. Postoperative pulmonary complications within 7 days after operation and re-hospitalization within 30 days were recorded. The time to first flatus, postoperative length of hospital stay and occurrence of adverse reactions (dizziness, nausea, vomiting) within 3 days after surgery were also recorded. Results:Compared with control group, FVC, FEV 1 and FEF 25%-75% were significantly increased postoperatively, the time to recovery of 80% FVC, FEV 1 and FEF 25%-75% was shortened, postoperative SpO 2 and PaO 2 were increased, postoperative PaCO 2 was decreased, the consumption of intraoperative remifentanil, effective pressing times of patient-controlled analgesia, and the number of patients required rescue analgesia were reduced, the postoperative time to first flatus and length of hospital stay were shortened, and the incidence of adverse reactions and pulmonary complications was decreased ( P<0.05). Conclusions:Anterior quadratus lumborum block at the lateral supra-arcuate ligament can improve postoperative pulmonary function, reduce adverse reactions, and promote early recovery for the patients undergoing robot-assisted laparoscopic radical prostatectomy under general anesthesia.

Objective To investigate the effect of ultrasound-guided anterior quadratus lumborum block at lateral supra-arcuate ligament on postoperative analgesia and inflammation response in elderly patients undergoing robot-assisted laparoscopic radical prostatectomy.Methods A total of 60 elderly patients who had undergone robot-assisted laparoscopic radical prostatectomy from June 2022 to June 2023 were randomly divided into a group of ultra-sound-guided anterior quadratus lumborum block at lateral supra-arcuate ligament combined with general anesthesia(observation group,n = 30)and a general anesthesia group(control group,n = 30).Both groups received patient-controlled intravenous analgesia after surgery.The first compression time of an analgesic pump and the numbers of effective compression and remedial analgesia were recorded.The VAS scores at postsurgical hours 2,12,24,and 48 during rest and coughing were recorded.Interleukin-6(IL-6)and systemic immunoinflammatory index(SII)at one day before surgery and two hours,one day and three days after surgery were recorded.Anal exhaust time,length of postoperative hospital stay and occurrence of adverse reactions were recorded.Results The observation group,as compared with the control group,had significantly longer first compression time of an analgesic pump and had fewer numbers of effective compressions and remedial analgesic administrations(P<0.05).The VAS scores during rest and coughing in the observation group were lower than those in the control group at postsurgical hours 2,12,24,and 48(P<0.05).As compared with one day before surgery,both IL-6 and SII in the two groups increased at 2 hours,1,and 3 days after surgery,but the changes in the observation group were lower than those in the control group(P<0.05).As compared with the control group,the observation group had shorter anal exhaust time and length of postoperative hospital stay,and a lower incidence of adverse reactions(P<0.05).Conclusions Ultrasound-guided anterior quadratus lumborum block at lateral supra-arcuate ligament can provide better postoperative analgesia,reduce inflammatory response and accelerate postoperative recovery in elderly patients undergoing robot-assisted laparoscopic radical prostatectomy.

ObjectiveTo analyze the causes of occupational acute 1,2-dichloroethane (1,2-DCE) poisoning accident during the use of polyurethane grouting materials for waterproof plugging operation in the construction industry. Methods By combining the clinical symptoms of the patient, worksite survey of occupational health and workplace occupational hazards monitoring method, the cause of an occupational acute 1,2-DCE poisoning accident was investigated at a construction site during the use of polyurethane grouting material for waterproofing and plugging operations. Results The patient was engaged in waterproof grouting work using polyurethane grouting material. The main volatile organic components in the raw materials were 1,2-DCE, with traces of dichloromethane, methyl acetate and others. The result of post-incident on-site investigation showed that the short-term exposure concentration of 1,2-DCE in the workplace air was 578.70 mg/m³, which was more than 30 times higher than the national occupational health standard limit. The mass concentration of 1,2-DCE in the patient's blood was 230 μg/L. Combined with the patient's occupational hazard exposure history, clinical manifestations, worksite survey of occupational health, and laboratory test results, according to GBZ 39-2016 Diagnosis of Occupational Acute 1,2-Dichloroethane Poisoning, this incident was diagnosed as a severe occupational acute 1,2-DCE poisoning event caused by the use of inferior polyurethane grouting material. Conclusion The excessive concentration of 1,2-DCE in the workplace air is the main cause of this poisoning accident. Construction sites with confined space operations should improve various occupational health management systems, occupational health engineering protective facilities, and personal protective equipment must be provided for workers.

Objective:To screen and verify the key radioresistance genes regulated by m6A methylation in nasopharyngeal carcinoma (NPC) based on the chip data and cell experiments.Methods:The microarray data of NPC radioresistance genes, m6A regulated genes and mRNA expression profiles of NPC genes were downloaded from Gene Expression Omnibus (GEO) database. The differential genes were screened and statistically analyzed by R software. The biological processes, signal pathways and interaction networks of these genes were analyzed by bioinformatics. The m6A regulatory factors were knocked down and the radioresistant strains were constructed. The above m6A differential radioresistant genes of NPC were screened and verified by real-time reverse transcription PCR (qRT-PCR) and Western blot. The m6A modification of screened genes and their direct binding ability with methyltransferase 3 (METTL3) were verified by methylated RNA immunoprecipitation qPCR (MeRIP-qPCR). The siRNA of selected genes was transfected into NPC cells, and after treatment with ionizing radiation, cell proliferation was detected by CCK-8 assay and EdU, apoptosis and cell cycle were detected by flow cytometry, and radiosensitivity was detected by clone formation assay. The trend of differences in the abundance of Fe 2+ and lipid peroxidation between the control and EGLN3 knockdown groups after ionizing radiation treatment was compared by paired t-test. Results:Chip data GSE48501 intersected with GSE200792 and GSE53819 to obtain 6 differential genes, including EGLN3, FOSL2, ADM, JUN, VEGFA and PRDM1. The target genes of EGLN3 and FOSL2 were further screened by TNMplot and KMplot, etc. The mRNA of the target genes directly bound to METTL3 and were subjected to its mediated modification of m6A. The target genes were up-regulated in the parental cells after irradiation in a dose and time gradient manner, which were also significantly up-regulated in radioresistant cells. After EGLN3 and FOSL2 were down regulated, the proliferation activity of NPC cells was more significantly decreased after irradiation, and the radiosensitization ratio was statistically significant compared with that of NPC cells without EGLN3 and FOSL2 down-regulation. After irradiation, EGLN3 down-regulated NPC cells significantly down-regulated glutathione peroxidase 4 (GPX4) expression, increased the abundance of Fe 2+ and lipid peroxidation, which played a role in radiosensitization by inducing ferroptosis. Conclusions:EGLN3 and FOSL2 play a role in radioresistance in NPC through METTL3 mediated m6A methylation. Down-regulation of EGLN3 combined with ionizing radiation can increase the intracellular Fe 2+ abundance and lipid peroxidation and down-reuglate the expression of GPX4 in NPC cells, which can enhance radiosensitization for NPC radiotherapy by the ferroptosis pathway.