Objective To design and evaluate the clinical application efficacy of a novel bilateral-separation endotracheal tube fixation device and provide references for clinical practice.Methods Using convenient sampling,60 patients from the Neurological Intensive Care Unit of a tertiary-level hospital in Zhengzhou were selected from May to December 2024.Patients were randomly divided into an experimental group(n=30)and a control group(n=30).The experimental group utilized the novel bilateral-separation endotracheal tube fixation device,while the control group employed traditional bandage fixation methods.Differences in fixation time,tube displacement,and intubation duration were compared between the 2 groups.Results The experimental group demonstrated significantly shorter tube fixation times compared to the control group(P＜0.05).However,no statistically significant differences were observed between the groups regarding intubation duration and tube displacement(P＞0.05).Conclusion The novel bilateral-separation endotracheal tube fixation device can reduce tube fixation time for patients in neurological intensive care and enhance nurse satisfaction.Despite not showing advantages in preventing tube displacement,the device still presents promising potential for broad clinical application.

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Objective To investigate the pathogenesis of high-altitude cerebral edema(HACE)and develop new therapeutic strategies.Methods Male Sprague-Dawley(SD)rats of 6 weeks old were selected and placed in a hypobaric chamber.The rats were exposed to the high-altitude environment of 7000 m above sea level for 3 days for HACE modeling.Whether the HACE model was successfully established in the rats was evaluated by measuring brain water content,the degree of disruption to the blood-brain barrier(BBB),and brain tissue Nissl staining.The experimental animals were divided into four groups,with 28 rats in each group.The blank control group was exposed to a normobaric and normoxic environment simulating the conditions at 500 m above sea level for 3 d.The other groups,including a model group(the HACE group),a bumetanide group(the positive control group),and a XH-6003 treatment group,were placed at an altitude of 7 000 m above sea level and were injected with normal saline,bumetanide,and XH-6003,a new type of Na-K-2C1 cotransporter 1(NKCC1)inhibitor,via the tail vein,respectively,twice daily for 3 d.The experimental animals were taken out of the hypobaric chamber for testing after 3 d.The primary outcome measures included brain water content,BBB permeability,changes in brain tissue morphology,and the expression levels of aquaporin-4(AQP4)and NKCC1.The secondary outcome measures included behavioral changes,apoptosis,and oxidative stress markers.Results The HACE rat model was successfully established.The model group exhibited increased brain water content(P＜0.0001),BBB disruption(P＜0.0001),impairment in learning skills and memory(P＜0.001),and anxiety/depression-like behaviors(P＜0.01).qPCR results showed significantly increased expression of NKCC1 and AQP4 in the brain tissue of the model group(P＜0.01).Pathology examination revealed neuronal and glial cell damage in the hippocampus of the model group(P＜0.01).Treatment with XH-6003,the NKCC1 inhibitor,reversed brain water content,BBB disruption,and neuronal and glial cell damage to a certain degree(P＜0.05),decreased the expression of NKCC1 and AQP4 in the brain tissue(P＜0.01),and inhibited apoptosis-related proteins.Among the oxidative stress indices,only glutathione(GSH)showed improvement(P＜0.001).Rats treated with XH-6003 showed functional improvement only in the time spent exploring novel objects,while other behavioral outcomes remained unchanged.Conclusion HACE is associated with the activation of the NKCC1/AQP4 pathway.Inhibition of this pathway alleviates brain edema,BBB disruption,and neuronal and glial cell damage.These findings suggest that XH-6003 holds potential as a therapeutic strategy for HACE at the cellular and molecular levels,but its effects in improving HACE-related behavioral disorders warrant further investigation.

Objective To design and evaluate the clinical application efficacy of a novel bilateral-separation endotracheal tube fixation device and provide references for clinical practice.Methods Using convenient sampling,60 patients from the Neurological Intensive Care Unit of a tertiary-level hospital in Zhengzhou were selected from May to December 2024.Patients were randomly divided into an experimental group(n=30)and a control group(n=30).The experimental group utilized the novel bilateral-separation endotracheal tube fixation device,while the control group employed traditional bandage fixation methods.Differences in fixation time,tube displacement,and intubation duration were compared between the 2 groups.Results The experimental group demonstrated significantly shorter tube fixation times compared to the control group(P＜0.05).However,no statistically significant differences were observed between the groups regarding intubation duration and tube displacement(P＞0.05).Conclusion The novel bilateral-separation endotracheal tube fixation device can reduce tube fixation time for patients in neurological intensive care and enhance nurse satisfaction.Despite not showing advantages in preventing tube displacement,the device still presents promising potential for broad clinical application.

With the changing disease spectrum, the incidence of tumors is increasing and tends to occur among the youth. The long-term survival rate of patients with cancer has increased significantly, and attention to their reproductive rights is growing. Surgery, chemotherapy, radiotherapy, immunotherapy, and molecular targeted therapy are the conventional treatment methods for cancer, with each exerting different effects on the fertility of patients. Common fertility preservation techniques currently include sperm cryopreservation, embryo and oocyte cryopreservation, ovarian tissue cryopreservation, uterine transplantation, and assisted reproductive technology. This article systematically summarizes the influence of different antitumor treatments on fertility, as well as the current status and prospects of fertility preservation in patients with cancer. This study aims to improve cooperation between clinical oncologists and reproductive medicine doctors to enhance fertility preservation for patients with cancer.

Cartilage is solid connective tissue that recovers slowly from injury,and pain and dysfunction from cartilage damage affect many people.The treatment of cartilage injury is clinically challenging and there is no optimal solution,which is a hot research topic at present.With the rapid development of 3D printing technology in recent years,3D bioprinting can better mimic the complex microstructure of cartilage tissue and thus enabling the anatomy and functional regeneration of damaged cartilage.This article reviews the methods of 3D printing used to mimic cartilage structures,the selection of cells and biological factors,and the development of bioinks and advances in scaffold structures,with an emphasis on how 3D printing structure provides bioactive cargos in each stage to enhance the effect.Finally,clinical applications and future development of simulated cartilage printing are introduced,which are expected to provide new insights into this field and guide other researchers who are engaged in cartilage repair.

Cartilage is solid connective tissue that recovers slowly from injury, and pain and dysfunction from cartilage damage affect many people. The treatment of cartilage injury is clinically challenging and there is no optimal solution, which is a hot research topic at present. With the rapid development of 3D printing technology in recent years, 3D bioprinting can better mimic the complex microstructure of cartilage tissue and thus enabling the anatomy and functional regeneration of damaged cartilage. This article reviews the methods of 3D printing used to mimic cartilage structures, the selection of cells and biological factors, and the development of bioinks and advances in scaffold structures, with an emphasis on how 3D printing structure provides bioactive cargos in each stage to enhance the effect. Finally, clinical applications and future development of simulated cartilage printing are introduced, which are expected to provide new insights into this field and guide other researchers who are engaged in cartilage repair.

Na⁺/H⁺ antiporter (NHX) gene subfamily plays an important role in plant response to salt stress. In this study, we identified the NHX gene family members of Chinese cabbage and analyzed the expression patterns of BrNHXs gene in response to abiotic stresses such as high temperature, low temperature, drought and salt stress. The results showed that there were 9 members of the NHX gene family in Chinese cabbage, which were distributed on 6 chromosomes respectively. The number of amino acids was 513-1 154 aa, the relative molecular weight was 56 804.22-127 856.66 kDa, the isoelectric point was 5.35-7.68. Members of BrNHX gene family mainly existed in vacuoles, the gene structure is complete, and the number of exons is 11-22. The secondary structures of the proteins encoded by the NHX gene family in Chinese cabbage had alpha helix, beta turn and random coil, and the alpha helix occurred more frequently. Quantitative real-time PCR (qRT-PCR) analysis showed that the gene family members had different responses to high temperature, low temperature, drought and salt stress, and their expression levels differed significantly in different time periods. BrNHX02 and BrNHX09 had the most significant responses to these four stresses, and their expression levels were significantly up-regulated at 72 h after treatments, which could be used as candidate genes to further verify their functions.
Genome, Plant ; Multigene Family ; Stress, Physiological/genetics* ; Brassica/metabolism* ; Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/metabolism*

Objective:To establish a patient-derived xenograft (PDX) humanized mouse model for hepatoblastoma in children. In addition, compare the biological consistency between successfully modeled PDX tumors and primary tumors in children while comparing and analyzing the influence of PDX model modeling success as a key factor.Methods:A PDX tumor model was constructed from fresh tumor tissue samples from 39 children with hepatoblastoma. The tumor growth time and volume size were recorded in detail. Simultaneously, 39 children’s data were collected for experimental and clinical analysis. The difference in tumorigenesis rate between different parameters was analyzed by χ2 test (categorical variable). Continuous variables with a normal distribution were compared using the t-test. Results:After cell passage and pathological diagnosis, 21 cases of hepatoblastoma PDX models were successfully constructed, with a success rate of 53.8% (21/39). Tumor samples from each generation of successfully modeled PDX models had pathology results that were consistent with those of the corresponding primary tumors. The analysis of the key factors affecting the tumor formation rate of PDX revealed that the metastasis rate was more successful in primary tumors than in liver in situ tumors (7/8 vs. 14/31, P = 0.049). However, there was no significant difference between tumor formation rates and pathological subtypes. According to the PDX tumor formation group comparison between the primary tumor and the metastatic tumor, there was no statistically significant difference between the two groups in terms of tumor formation time and tumor volume. Hematoxylin-eosin staining in hepatoblastoma’s PDX mouse was consistent with the primary tumor. Immunohistochemistry positivity rates of four proteins, namely hepatocyte antigen (Hepatocyte), phosphatidylinositol glycan 3, β-catenin, and alpha-fetoprotein, in primary tumor tissues and PDX mouse models were 100% vs. 100%, 100% vs. 95.24%, 100% vs. 100%, and 95.24% vs. 85.71%, respectively. Conclusion:A PDX mouse model for hepatoblastoma has been successfully established in children. The tumor formation rate is high, with metastatic tumors having a higher tumor formation rate than primary tumors and transplanted tumors retaining the biological characteristics of primary tumors.