Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

Brain metastases are the most common intracranial tumors, and their incidence is increasing with the improvement of systemic treatments and survival rates. Optimal treatment usually requires a multidisciplinary approach, including radiotherapy, surgical resection, chemotherapy, targeted therapy, and immunotherapy. Stereotactic radiotherapy, compared to whole-brain radiotherapy, offers improved local control rates and reduced risk of neurocognitive impairment, and has become a new standard option for the treatment of brain metastases. Additionally, the widespread use of targeted and immune therapies in brain metastases has significantly improved the survival of some patients. This article reviews and integrates recent literature on the treatment of brain metastases and analyzes the role of stereotactic radiotherapy in comprehensive treatment, aiming to provide a reference for the selection of clinical treatment plans.

BackgroundPrevious studies have identified a close relationship among psychological neglect and abuse， negative affect， different stages of adolescence， and suicidal ideation. However， the mechanisms underlying the impact of psychological abuse and neglect on suicidal ideation among left-behind adolescents remain unclear， and this field of research is still in its relative infancy. ObjectiveTo explore the relationship between psychological neglect/abuse and suicidal ideation among left-behind adolescents， as well as the mediating role of negative affect and the moderating effect of different stages of adolescence， so as to provide insights for preventing and intervening suicidal ideation in this population. MethodsFrom November 2021 to May 2022， a cluster random sampling technique was utilized to select 2 309 left-behind adolescents in western China. Assessments were conducted using the Child Psychological Abuse and Neglect Scale （CPANS）， the Positive and Negative Suicide Ideation （PANSI） and the Positive and Negative Affect Schedule for Children （PANAS-C）. Spearman correlation coefficients were calculated across all samples， and Process 4.1 was employed to test the mediating role of negative affect and the moderating role of different stages of adolescence in the pathway linking psychological abuse/neglect to suicidal ideation. ResultsA total of 2 119 left-behind adolescents （mean age： 14.94±1.20 years） completed the study， with males comprising 51.34% （1 088/2 119） and females 48.66% （1 031/2 119）.Among left-behind adolescents， scores on CPANS psychological neglect subscale showed positive correlations with both psychological abuse subscale scores and PANAS-C negative affect subscale scores （r=0.446， 0.496， P<0.01）. Additionally， CPANS psychological neglect and psychological abuse subscale scores were also positively correlated with PANSI scores （r=0.487， 0.508， P<0.01）. Furthermore， PANAS-C negative affect subscale scores demonstrated a positive correlation with PANSI scores （r=0.499， P<0.01）. Negative affect partially mediated the relationship between psychological abuse/psychological neglect and suicidal ideation， with effect sizes of 0.166 （95% CI： 0.141~0.191） and 0.131 （95% CI： 0.112~0.152）. Different stages of adolescence moderated the latter part （negative emotion → suicidal ideation） of the indirect mediation path from psychological neglect to suicidal ideation through negative affect （β=-0.066， P<0.01）. ConclusionBoth psychological neglect and psychological abuse may influence suicidal ideation among left-behind adolescents via negative affect. Moreover， different stages of adolescence may moderate the indirect path from psychological neglect to suicide ideation through negative affect.

Objective To explore the potential cross-sectional categories of health promotion behaviors in patients after PCI and analyze their influencing factors,so as to provide a reference for formulating targeted interventions to improve health promotion behaviors in patients after PCI.Methods A total of 242 patients who underwent PCI surgery in the Department of Cardiovascular Medicine of a tertiary hospital in Sichuan Province from February to May 2024 were selected by convenience sampling method.The general information questionnaire,the health promotion lifestyle scale,the health literacy scale for patients with chronic diseases,and the perceived social support scale were used to conduct the survey.The potential profile analysis of health promotion behaviors in patients after PCI was carried out,and the influencing factors were explored by univariate analysis and multiple logistic regression analysis.Results A total of 230 patients after PCI completed the study.The results of potential profile analysis showed that the health promotion behaviors of patients after PCI could be divided into three potential profiles:"low health promotion-poor behavior group"(n=71,30.9%),"medium health promotion behavior group"(n=53,23.0%),and"high health promotion-positive behavior group"(n=106,46.1%).Logistic regression analysis showed that medical payment methods,the number of chronic diseases,whether they had received chronic disease-related knowledge guidance,health literacy,and social support were the influencing factors of the potential profile of health promotion behaviors of patients after PCI(all P<0.05).Conclusion The health promotion behaviors of patients after PCI have obvious categorical characteristics.Nursing staff should formulate personalized intervention strategies according to the characteristics and influencing factors of each category,improve the health literacy and comprehension of social support of patients after PCI,and then improve their health promotion behaviors.

BACKGROUND:Previous studies have found that for postmenopausal osteoporosis patients,the Bushen Jianpi Formula can help regulate serum osteoclast-and osteoblast-related factors and intestinal flora levels,improve clinical symptoms of patients and further improve efficacy.OBJECTIVE:To investigate the effect of Bushen Jianpi Formula on bone metabolism and bone microarchitecture in ovariectomized rats.METHODS:Twenty-four female SD rats were randomly divided into four groups by random number table method:sham operation group(n=6)was subjected to periovarian fat removal,and bilateral ovariectomy was performed in model group(n=6),alendronate group(n=6),and Bushen Jianpi Formula group(n=6).Five days after modeling,the Bushen Jianpi Formula group was given Bushen Jianpi Formula by intragastric administration(once a day).The alendronate sodium group was given alendronate by intragastric administration(once a week).The sham operation group and model group were given an equal volume of normal saline by intragastric administration(once a day)for 12 consecutive weeks.After intragastric administration,serum levels of procollagen Ⅰ N-terminal peptide,β-isomerized C-terminal telopeptide of type Ⅰ collagen degradation product,and tumor necrosis factor α were detected.The distal femur microstructure was detected by Micro-CT.The femoral tissue morphology was observed by hematoxylin-eosin staining.The expression of type Ⅰ collagen and tumor necrosis factorα in the femur was detected by immunohistochemical staining.RESULTS AND CONCLUSION:(1)The serum ELISA test showed that compared with the sham operation group,the level of procollagen Ⅰ N-terminal peptide in the model group decreased(P＜0.05),and the levels of degradation products of β-isomerized C-terminal telopeptide of type Ⅰ collagen and tumor necrosis factor α increased(P＜0.05).Compared with the model group,the levels of the procollagen Ⅰ N-terminal peptide in the Bushen Jianpi Formula group and the alendronate sodium group increased(P＜0.05),and the levels of β-isomerized C-terminal telopeptide of type Ⅰ collagen degradation products and tumor necrosis factor α decreased(P＜0.05).(2)Micro-CT three-dimensional reconstruction showed that compared with the sham operation group,the number of bone trabeculae in the model group was significantly reduced,the continuity was worsened,and the gaps were increased.Both alendronate sodium and Bushen Jianpi Formula had a positive improvement effect on this phenomenon.(3)Hematoxylin-eosin staining showed that compared with the sham operation group,the number of bone trabeculae in the model group was reduced and the shape became thinner,and the network structure was destroyed.Compared with the model group,the number of bone trabeculae in the Bushen Jianpi Formula group and the alendronate sodium group increased,the shape became thicker,and the reticular structure was restored.(4)Immunohistochemical staining showed that compared with the sham operation group,the expression of type Ⅰ collagen was reduced and tumor necrosis factor α expression was increased in the model group.Compared with the model group,the expression of type Ⅰ collagen increased and the expression of tumor necrosis factor α decreased in the Bushen Jianpi Formula group and the alendronate sodium group.The results show that the Bushen Jianpi Formula can effectively improve bone metabolism and bone microstructure in ovariectomized rats.

Objective To investigate the value of MRI of the sternal end of clavicle in bone age assessment in Chinese population,especially its applicability in the determination of criminal responsible age.Methods A total of 431 patients aged from 10.00 to 29.99 years with neck or chest MRI were retrospectively collected.According to the Schmeling grading method,the epiphyseal development of the clavicle MRI was divided into five grades.The consistency of methods was evaluated.The correlation and general descriptive analysis between MRI grades and age was analyzed.The sex difference was analyzed.Curve fitting was used to establish a nonlinear model between age and grades.Results The grades of clavicle MRI showed a significant age-related trend(Figure 2),and the correlation was 0.861(0.887 in males and 0.840 in females).Except for grade 1,there was no significant difference between males and females in other grades.The minimum age of male grade 3 was greater than 14 years old,and the minimum age of female grade 3 was greater than 16 years old.The minimum age in grade 4 and grade 5 was over 18 years old in both sexes.The best curve fitting model was cubic model for both sexes(R2=0.805 for men and 0.722 for women).Conclusion Clavicle MRI can be used for the assessment of bone age in Chinese population.Complete epiphyseal plate closure can be used as a reliable indicator for the determination of age at 18 years old,and it is expected to achieve radiation-free forensic bone age assessment.

Objective To explore the potential cross-sectional categories of health promotion behaviors in patients after PCI and analyze their influencing factors,so as to provide a reference for formulating targeted interventions to improve health promotion behaviors in patients after PCI.Methods A total of 242 patients who underwent PCI surgery in the Department of Cardiovascular Medicine of a tertiary hospital in Sichuan Province from February to May 2024 were selected by convenience sampling method.The general information questionnaire,the health promotion lifestyle scale,the health literacy scale for patients with chronic diseases,and the perceived social support scale were used to conduct the survey.The potential profile analysis of health promotion behaviors in patients after PCI was carried out,and the influencing factors were explored by univariate analysis and multiple logistic regression analysis.Results A total of 230 patients after PCI completed the study.The results of potential profile analysis showed that the health promotion behaviors of patients after PCI could be divided into three potential profiles:"low health promotion-poor behavior group"(n=71,30.9%),"medium health promotion behavior group"(n=53,23.0%),and"high health promotion-positive behavior group"(n=106,46.1%).Logistic regression analysis showed that medical payment methods,the number of chronic diseases,whether they had received chronic disease-related knowledge guidance,health literacy,and social support were the influencing factors of the potential profile of health promotion behaviors of patients after PCI(all P<0.05).Conclusion The health promotion behaviors of patients after PCI have obvious categorical characteristics.Nursing staff should formulate personalized intervention strategies according to the characteristics and influencing factors of each category,improve the health literacy and comprehension of social support of patients after PCI,and then improve their health promotion behaviors.

BACKGROUND:Previous studies have found that for postmenopausal osteoporosis patients,the Bushen Jianpi Formula can help regulate serum osteoclast-and osteoblast-related factors and intestinal flora levels,improve clinical symptoms of patients and further improve efficacy.OBJECTIVE:To investigate the effect of Bushen Jianpi Formula on bone metabolism and bone microarchitecture in ovariectomized rats.METHODS:Twenty-four female SD rats were randomly divided into four groups by random number table method:sham operation group(n=6)was subjected to periovarian fat removal,and bilateral ovariectomy was performed in model group(n=6),alendronate group(n=6),and Bushen Jianpi Formula group(n=6).Five days after modeling,the Bushen Jianpi Formula group was given Bushen Jianpi Formula by intragastric administration(once a day).The alendronate sodium group was given alendronate by intragastric administration(once a week).The sham operation group and model group were given an equal volume of normal saline by intragastric administration(once a day)for 12 consecutive weeks.After intragastric administration,serum levels of procollagen Ⅰ N-terminal peptide,β-isomerized C-terminal telopeptide of type Ⅰ collagen degradation product,and tumor necrosis factor α were detected.The distal femur microstructure was detected by Micro-CT.The femoral tissue morphology was observed by hematoxylin-eosin staining.The expression of type Ⅰ collagen and tumor necrosis factorα in the femur was detected by immunohistochemical staining.RESULTS AND CONCLUSION:(1)The serum ELISA test showed that compared with the sham operation group,the level of procollagen Ⅰ N-terminal peptide in the model group decreased(P＜0.05),and the levels of degradation products of β-isomerized C-terminal telopeptide of type Ⅰ collagen and tumor necrosis factor α increased(P＜0.05).Compared with the model group,the levels of the procollagen Ⅰ N-terminal peptide in the Bushen Jianpi Formula group and the alendronate sodium group increased(P＜0.05),and the levels of β-isomerized C-terminal telopeptide of type Ⅰ collagen degradation products and tumor necrosis factor α decreased(P＜0.05).(2)Micro-CT three-dimensional reconstruction showed that compared with the sham operation group,the number of bone trabeculae in the model group was significantly reduced,the continuity was worsened,and the gaps were increased.Both alendronate sodium and Bushen Jianpi Formula had a positive improvement effect on this phenomenon.(3)Hematoxylin-eosin staining showed that compared with the sham operation group,the number of bone trabeculae in the model group was reduced and the shape became thinner,and the network structure was destroyed.Compared with the model group,the number of bone trabeculae in the Bushen Jianpi Formula group and the alendronate sodium group increased,the shape became thicker,and the reticular structure was restored.(4)Immunohistochemical staining showed that compared with the sham operation group,the expression of type Ⅰ collagen was reduced and tumor necrosis factor α expression was increased in the model group.Compared with the model group,the expression of type Ⅰ collagen increased and the expression of tumor necrosis factor α decreased in the Bushen Jianpi Formula group and the alendronate sodium group.The results show that the Bushen Jianpi Formula can effectively improve bone metabolism and bone microstructure in ovariectomized rats.

Objective To investigate the value of MRI of the sternal end of clavicle in bone age assessment in Chinese population,especially its applicability in the determination of criminal responsible age.Methods A total of 431 patients aged from 10.00 to 29.99 years with neck or chest MRI were retrospectively collected.According to the Schmeling grading method,the epiphyseal development of the clavicle MRI was divided into five grades.The consistency of methods was evaluated.The correlation and general descriptive analysis between MRI grades and age was analyzed.The sex difference was analyzed.Curve fitting was used to establish a nonlinear model between age and grades.Results The grades of clavicle MRI showed a significant age-related trend(Figure 2),and the correlation was 0.861(0.887 in males and 0.840 in females).Except for grade 1,there was no significant difference between males and females in other grades.The minimum age of male grade 3 was greater than 14 years old,and the minimum age of female grade 3 was greater than 16 years old.The minimum age in grade 4 and grade 5 was over 18 years old in both sexes.The best curve fitting model was cubic model for both sexes(R2=0.805 for men and 0.722 for women).Conclusion Clavicle MRI can be used for the assessment of bone age in Chinese population.Complete epiphyseal plate closure can be used as a reliable indicator for the determination of age at 18 years old,and it is expected to achieve radiation-free forensic bone age assessment.