Objective To understand the driver gene mutation status in patients with non-small cell lung cancer (NSCLC) in Xi'an City, and to analyze the association with environmental exposure factors. Methods A total of 305 NSCLC patients admitted to the First Affiliated Hospital of the Air Force Medical University from January 2019 to December 2023 were included. The driver gene mutation status was observed, and the relationship with environmental exposure factors was analyzed. Results The driver gene mutation rate of 305 patients was 46.89%, with EGFR gene mutation accounting for the highest proportion, and 4 cases of gene co-mutations were detected. There was a difference in gender among patients with different single drive gene mutations (P<0.05), and the proportion of EGFR in women was significantly higher (P<0.05). Univariate analysis showed that there were statistical differences in family history, smoking history, long-term cooking history, and fried smoked food intake between patients with driver gene mutation and patients without driver gene mutation (P<0.05). Logistic regression analysis suggested that long-term cooking history (OR=2.392), and fried smoked food intake (OR=2.849) were the environmental exposure factors affecting EGFR gene mutation (P<0.05), and smoking history (OR=1.377) was an environmental exposure factor of KRAS gene mutation (P<0.05). Conclusion EGFR gene mutation accounts for the highest proportion of NSCLC patients in Xi'an City, and is mainly female. Long-term cooking history, and fried smoked food intake are related to EGFR gene mutation. There is a certain association between smoking history and KRAS gene mutation.

In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

OBJECTIVE To analyze and identify the metabolites of pirtobrutinib （PTN） in rats， and clarify the possible metabolic pathways of PTN in rats. METHODS Six rats were intragastrically administered with 10 mg/kg PTN suspension. Blood samples were collected from the rats 30 minutes before administration and at 0.25， 0.5， 1， 2， 4， 6， 8， 12， 24 hours after administration. Urine and feces samples were collected 12 hours before administration and 24 hours after administration. UHPLC- Orbitrap Exploris 240 system combined with Compound Discoverer 3.0 and Xcalibur 2.0 software were adopted for structural identification and metabolic pathway analysis of PTN metabolites in rat plasma， urine， and feces. RESULTS A total of 29 PTN metabolites were identified， including 17， 19 and 22 metabolites in plasma， urine and feces， respectively. The metabolic pathways of PTN mainly included oxidation， sulfation， glucuronidation， etc.， and its metabolites were mostly combination products of two or more different metabolic forms. In detail， a total of 26 metabolites were associated with phase Ⅰ metabolic reactions （14 oxidation metabolites， 9 reduction/dehydrogenation metabolites， 8 demethylation metabolites， and 5 hydrolysis metabolites）. Meanwhile， a total of 20 products were involved in phase Ⅱ metabolites （14 sulfation metabolites and 8 glucuronic acid binding metabolites）. CONCLUSIONS PTN exhibits a diverse range of metabolites in rat fecal samples， with the primary metabolic pathways being oxidation， sulfation， glucuronidation， and others.

BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Objective To construct a perioperative blood pressure management plan for patients undergoing carotid artery stenting(CAS)and evaluate its application effectiveness,and to provide references for clinical practice.Methods The relevant literature on perioperative blood pressure management for CAS patients was retrieved from domestic and foreign databases,and a preliminary draft of a perioperative blood pressure management plan for CAS patients was constructed.The preliminary draft was discussed and modified through expert meetings,and 2 rounds of expert inquiries were conducted using the Delphi method from June 2023 to August 2023 to determine the final plan.32 patients who received CAS in the neurology department of a tertiary comprehensive hospital in Zhejiang Province were selected from May to July 2024 as an experimental group,and 33 patients who received CAS in the same ward from January to March 2024 as a control group.The experimental group applied the constructed CAS patient perioperative blood pressure management plan,while the control group applied routine perioperative nursing measures.The incidence of postoperative hypertension,postoperative hypotension,and postoperative adverse events was compared between 2 groups.Results A total of 13 experts completed 2 rounds of inquiries.The effective questionnaire response rate for the second round of inquiry was 100％,with an authority coefficient of 0.897.The coefficients of variation for the importance and feasibility scores of each item were 0～0.19 and 0～0.18,respectively,and the Kendall harmony coefficients were 0.224 and 0.201,respectively(P＜0.05).The final construction plan includes 3 primary indicators,15 secondary indicators,and 40 tertiary indicators.Ultimately,32 cases were included in the experimental group and 33 cases in the control group.The incidence of postoperative hypertension,postoperative hypotension,and adverse events in the experimental group was lower than that in the control group,and the difference was statistically significant(P＜0.05).Conclusion The perioperative blood pressure management plan for CAS patients constructed in this study has good scientificity and practicality,which can improve the stability of patients'perioperative blood pressure and reduce the occurrence of adverse events.

Objective To explore the longitudinal changes of symptoms after discharge in patients with daytime lung cancer surgery by factor analysis,in order to strengthen nursing countermeasures and improve the quality of life of patients.Methods Patients who underwent day surgery in the thoracic surgery department of a tertiary general hospital in Zhejiang Province from October 2023 to January 2024 were selected using convenience sampling.On the 1st,3rd,14th and 30th day after discharge,the general information questionnaire and the postoperative symptom inventory for patients with lung cancer were used for investigation.Exploratory factor analysis was performed to extract the symptom clusters.Results A total of 227 patients were followed up in this study,including 19 shed cases and 2 excluded cases,and 206 patients were finally included.The percentage of the 9 major symptoms of patients with daytime lung cancer surgery after discharge showed dynamic changes.The highest percentage symptom on the 1st day after discharge was pain in 197 cases(95.63％).The highest percentage on the 30th day after discharge was cough in 129 cases(62.62％).The results of exploratory factor analysis were P＜0.001 and KMO＞0.500 for Bartlett's test of sphericity on days 1,3,and 14 after discharge,except for P=0.874 and KMO=0.495 on day 30,with digestive and respiratory symptom clusters on day 1;respiratory,digestive,and fatigue symptom clusters on day 3;fatigue and respiratory symptom clusters on day 14.Conclusion The single symptom and symptom clusters of patients with daytime lung cancer surgery after discharge showed dynamic changes at different time points.Therefore,in clinical work,targeted intervention strategies should be adopted,and precise symptom management should be implemented according to the characteristics of symptom clusters in different periods of discharge of patients undergoing daytime lung cancer surgery,so as to reduce the symptom burden of patients.

Objective To construct a perioperative blood pressure management plan for patients undergoing carotid artery stenting(CAS)and evaluate its application effectiveness,and to provide references for clinical practice.Methods The relevant literature on perioperative blood pressure management for CAS patients was retrieved from domestic and foreign databases,and a preliminary draft of a perioperative blood pressure management plan for CAS patients was constructed.The preliminary draft was discussed and modified through expert meetings,and 2 rounds of expert inquiries were conducted using the Delphi method from June 2023 to August 2023 to determine the final plan.32 patients who received CAS in the neurology department of a tertiary comprehensive hospital in Zhejiang Province were selected from May to July 2024 as an experimental group,and 33 patients who received CAS in the same ward from January to March 2024 as a control group.The experimental group applied the constructed CAS patient perioperative blood pressure management plan,while the control group applied routine perioperative nursing measures.The incidence of postoperative hypertension,postoperative hypotension,and postoperative adverse events was compared between 2 groups.Results A total of 13 experts completed 2 rounds of inquiries.The effective questionnaire response rate for the second round of inquiry was 100％,with an authority coefficient of 0.897.The coefficients of variation for the importance and feasibility scores of each item were 0～0.19 and 0～0.18,respectively,and the Kendall harmony coefficients were 0.224 and 0.201,respectively(P＜0.05).The final construction plan includes 3 primary indicators,15 secondary indicators,and 40 tertiary indicators.Ultimately,32 cases were included in the experimental group and 33 cases in the control group.The incidence of postoperative hypertension,postoperative hypotension,and adverse events in the experimental group was lower than that in the control group,and the difference was statistically significant(P＜0.05).Conclusion The perioperative blood pressure management plan for CAS patients constructed in this study has good scientificity and practicality,which can improve the stability of patients'perioperative blood pressure and reduce the occurrence of adverse events.

Objective To explore the longitudinal changes of symptoms after discharge in patients with daytime lung cancer surgery by factor analysis,in order to strengthen nursing countermeasures and improve the quality of life of patients.Methods Patients who underwent day surgery in the thoracic surgery department of a tertiary general hospital in Zhejiang Province from October 2023 to January 2024 were selected using convenience sampling.On the 1st,3rd,14th and 30th day after discharge,the general information questionnaire and the postoperative symptom inventory for patients with lung cancer were used for investigation.Exploratory factor analysis was performed to extract the symptom clusters.Results A total of 227 patients were followed up in this study,including 19 shed cases and 2 excluded cases,and 206 patients were finally included.The percentage of the 9 major symptoms of patients with daytime lung cancer surgery after discharge showed dynamic changes.The highest percentage symptom on the 1st day after discharge was pain in 197 cases(95.63％).The highest percentage on the 30th day after discharge was cough in 129 cases(62.62％).The results of exploratory factor analysis were P＜0.001 and KMO＞0.500 for Bartlett's test of sphericity on days 1,3,and 14 after discharge,except for P=0.874 and KMO=0.495 on day 30,with digestive and respiratory symptom clusters on day 1;respiratory,digestive,and fatigue symptom clusters on day 3;fatigue and respiratory symptom clusters on day 14.Conclusion The single symptom and symptom clusters of patients with daytime lung cancer surgery after discharge showed dynamic changes at different time points.Therefore,in clinical work,targeted intervention strategies should be adopted,and precise symptom management should be implemented according to the characteristics of symptom clusters in different periods of discharge of patients undergoing daytime lung cancer surgery,so as to reduce the symptom burden of patients.

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77's therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.

As the central organ of metabolism, the liver plays a pivotal role in the regulation of the synthesis and metabolism of various nutrients within the body. Ferroptosis, as a newly discovered type of programmed cell death caused by the accumulation of iron-dependent lipid peroxides, is involved in the physiological and pathological processes of a variety of acute and chronic liver diseases. Ferroptosis can accelerate the pathogenetic process of acute liver injury, metabolic associated fatty liver disease, alcoholic liver disease, viral hepatitis, and autoimmune hepatitis; while it can slower disease progression in advanced liver fibrosis and hepatocellular carcinoma. This suggests that targeted regulation of ferroptosis may impact the occurrence and development of various liver diseases. This article reviews the latest research progress of ferroptosis in various liver diseases, including acute liver injury, metabolic associated fatty liver disease, alcoholic liver disease, viral hepatitis, autoimmune hepatitis, liver fibrosis and hepatocellular carcinoma. It aims to provide insights for the prevention and treatment of acute and chronic liver diseases through targeting ferroptosis.
Humans ; Liver Diseases/etiology* ; Ferroptosis/physiology* ; Liver Neoplasms/pathology* ; Carcinoma, Hepatocellular/pathology* ; Liver Cirrhosis/etiology* ; Liver/pathology* ; Hepatitis, Autoimmune/metabolism* ; Liver Diseases, Alcoholic/metabolism*