BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Osteosarcoma (OS), chondrosarcoma (CS), and Ewing sarcoma (ES) represent primary malignant bone tumors and pose significant challenges in oncology research and clinical management. Conventional research methods, such as two-dimensional (2D) cultured tumor cells and animal models, have limitations in recapitulating the complex tumor microenvironment (TME) and often fail to translate into effective clinical treatments. The advancement of three-dimensional (3D) culture technology has revolutionized the field by enabling the development of in vitro constructed bone tumor models that closely mimic the in vivo TME. These models provide powerful tools for investigating tumor biology, assessing therapeutic responses, and advancing personalized medicine. This comprehensive review summarizes the recent advancements in research on 3D tumor models constructed in vitro for OS, CS, and ES. We discuss the various techniques employed in model construction, their applications, and the challenges and future directions in this field. The integration of advanced technologies and the incorporation of additional cell types hold promise for the development of more sophisticated and physiologically relevant models. As research in this field continues to evolve, we anticipate that these models will play an increasingly crucial role in unraveling the complexities of malignant bone tumors and accelerating the development of novel therapeutic strategies.
Bone Neoplasms/pathology* ; Humans ; Osteosarcoma/pathology* ; Tumor Microenvironment ; Sarcoma, Ewing/pathology* ; Chondrosarcoma/pathology* ; Animals ; Cell Culture Techniques/methods* ; Cell Culture Techniques, Three Dimensional/methods* ; Cell Line, Tumor

ObjectiveTo investigate the mechanism of action of Bushen Huoxue prescription （BSHXP） in regulating premature ovarian failure in rats through the PTEN-induced kinase 1 （PINK1）/Parkinson's protein （Parkin） signaling pathway-mediated mitophagy. MethodsA total of 48 rats were randomly divided into a blank group consisting of eight rats， while the remaining 40 rats underwent modeling. The modeling group was intraperitoneally injected with 4 mg·kg^-1 cisplatin solution， followed by a second injection one week later， for a total of two injections. The estrous cycle was observed through vaginal smears for 14 consecutive days to determine whether the modeling was successful. The successfully modeled rats were randomly divided into a model group， groups receiving low， medium， and high doses of BSHXP at 9.72， 19.44， and 38.88 g·kg^-1·d^-1 （BSHXP-L， BSHXP-M， and BSHXP-H groups）， and a positive control group treated with estradiol valerate （0.09 mg·kg^-1·d^-1）， for 21 consecutive days. The body weight of the rats was measured weekly. After the final administration， rats were anesthetized， and their blood and ovaries were collected. The ovarian weight was measured. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of anti-Müllerian hormone （AMH）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E₂）. Assay kits were used to measure the levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in the rat serum. Hematoxylin-eosin （HE） staining was used to observe the morphological changes in the ovaries. Immunohistochemistry （IHC） was performed to detect microtubule autophagy-related protein 1 light chain 3B（LC3B） protein expression in ovarian tissue， and electron microscopy was employed to examine the mitochondrial and autophagosome changes in the rat ovaries. Western blot was used to detect the protein expression of PINK1， Parkin， LC3B， and p62. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of PINK1， Parkin， LC3B， and p62 in ovarian tissue. ResultsCompared with the blank group， the model group showed significant reductions in body weight， weight gain， and ovarian weight （P<0.01）， along with decreased serum AMH and E₂ levels （P<0.01）， while FSH and LH levels were increased （P<0.01）. Serum MDA levels were significantly increased （P<0.01）， and SOD levels were significantly reduced （P<0.01）. The ovarian tissue structure was disordered， and the zona pellucida was wrinkled into an irregular acidophilic annular object， accompanied by an increased number of closed follicles. Electron microscopy showed mitochondrial swelling， unclear structure， and no obvious autophagosomes and autolysosome structures. The proteins and mRNA expression levels of PINK1， Parkin， LC3B， and p62 in the ovarian tissue were significantly reduced （P<0.01）. Compared with the model group， all treatment groups showed varying degrees of increases in body weight and ovarian weight （P<0.05， P<0.01）. Except for the BSHXP-L group， all treatment groups showed increased body weight gain （P<0.01）. All treatment groups showed significantly increased serum AMH and decreased FSH levels （P<0.01）. Except for the BSHXP group， all treatment groups showed varying degrees of increase and decrease in serum E₂ and LH levels （P<0.05， P<0.01）. All treatment groups showed reduced serum MDA levels （P<0.01）， while the BSHXP-M， BSHXP-H， and the positive control groups demonstrated improved serum SOD levels （P<0.05， P<0.01）. All treatment groups showed an increased number of follicles at all stages， visible mature follicles， and a decreased number of closed follicles. Electron microscopy showed relieved mitochondrial swelling， morphology close to normal， clear structure， and visible formation of autolysosomes in all treatment groups. Additionally， the protein and mRNA expression levels of PINK1， Parkin， LC3B， and p62 in ovarian tissue were significantly increased （P<0.05， P<0.01）. ConclusionBSHXP may improve ovarian function in rats with premature ovarian failure by regulating the PINK1/Parkin signaling pathway， activating mitochondrial autophagy， and reducing oxidative damage.

ObjectiveTo investigate the mechanism of action of Bushen Huoxue prescription （BSHXP） in regulating premature ovarian failure in rats through the PTEN-induced kinase 1 （PINK1）/Parkinson's protein （Parkin） signaling pathway-mediated mitophagy. MethodsA total of 48 rats were randomly divided into a blank group consisting of eight rats， while the remaining 40 rats underwent modeling. The modeling group was intraperitoneally injected with 4 mg·kg^-1 cisplatin solution， followed by a second injection one week later， for a total of two injections. The estrous cycle was observed through vaginal smears for 14 consecutive days to determine whether the modeling was successful. The successfully modeled rats were randomly divided into a model group， groups receiving low， medium， and high doses of BSHXP at 9.72， 19.44， and 38.88 g·kg^-1·d^-1 （BSHXP-L， BSHXP-M， and BSHXP-H groups）， and a positive control group treated with estradiol valerate （0.09 mg·kg^-1·d^-1）， for 21 consecutive days. The body weight of the rats was measured weekly. After the final administration， rats were anesthetized， and their blood and ovaries were collected. The ovarian weight was measured. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of anti-Müllerian hormone （AMH）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E₂）. Assay kits were used to measure the levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in the rat serum. Hematoxylin-eosin （HE） staining was used to observe the morphological changes in the ovaries. Immunohistochemistry （IHC） was performed to detect microtubule autophagy-related protein 1 light chain 3B（LC3B） protein expression in ovarian tissue， and electron microscopy was employed to examine the mitochondrial and autophagosome changes in the rat ovaries. Western blot was used to detect the protein expression of PINK1， Parkin， LC3B， and p62. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of PINK1， Parkin， LC3B， and p62 in ovarian tissue. ResultsCompared with the blank group， the model group showed significant reductions in body weight， weight gain， and ovarian weight （P<0.01）， along with decreased serum AMH and E₂ levels （P<0.01）， while FSH and LH levels were increased （P<0.01）. Serum MDA levels were significantly increased （P<0.01）， and SOD levels were significantly reduced （P<0.01）. The ovarian tissue structure was disordered， and the zona pellucida was wrinkled into an irregular acidophilic annular object， accompanied by an increased number of closed follicles. Electron microscopy showed mitochondrial swelling， unclear structure， and no obvious autophagosomes and autolysosome structures. The proteins and mRNA expression levels of PINK1， Parkin， LC3B， and p62 in the ovarian tissue were significantly reduced （P<0.01）. Compared with the model group， all treatment groups showed varying degrees of increases in body weight and ovarian weight （P<0.05， P<0.01）. Except for the BSHXP-L group， all treatment groups showed increased body weight gain （P<0.01）. All treatment groups showed significantly increased serum AMH and decreased FSH levels （P<0.01）. Except for the BSHXP group， all treatment groups showed varying degrees of increase and decrease in serum E₂ and LH levels （P<0.05， P<0.01）. All treatment groups showed reduced serum MDA levels （P<0.01）， while the BSHXP-M， BSHXP-H， and the positive control groups demonstrated improved serum SOD levels （P<0.05， P<0.01）. All treatment groups showed an increased number of follicles at all stages， visible mature follicles， and a decreased number of closed follicles. Electron microscopy showed relieved mitochondrial swelling， morphology close to normal， clear structure， and visible formation of autolysosomes in all treatment groups. Additionally， the protein and mRNA expression levels of PINK1， Parkin， LC3B， and p62 in ovarian tissue were significantly increased （P<0.05， P<0.01）. ConclusionBSHXP may improve ovarian function in rats with premature ovarian failure by regulating the PINK1/Parkin signaling pathway， activating mitochondrial autophagy， and reducing oxidative damage.

Objective:To explore the value of the vesical imaging-reporting and data system (VI-RADS) score based on multiparametric MRI (mpMRI) combined with quantitative tumor MRI parameters in assessing the muscle invasion of bladder cancer.Methods:The study was a case-control study. The data of 87 bladder cancer patients confirmed by pathology who underwent mpMRI of the bladder were retrospectively collected from the First Medical Center of Chinese PLA General Hospital between January 2019 and April 2023 The pathological findings were used as the gold standard to categorize them into the muscle invasive bladder cancer (MIBC) group (29 cases) and non-muscle invasive bladder cancer (NMIBC) group (58 cases). Quantitative parameters were measured based on preoperative mpMRI images, including the length of tumor bladder wall contact, the perpendicular distance between the bladder tumor and the tangent of the bladder wall, the maximal diameter of the bladder tumor, and the volume of the bladder tumor. Bladder cancer was classified according to the VI-RADS scoring criteria. The Mann-Whitney U test was used for intergroup comparisons. Multivariate logistic regression analysis was performed to obtain the independent risk factors related to muscle invasion of bladder cancer and to establish the model. The receiver operating characteristic curves were analyzed for MRI quantitative parameters and logistic regression models, and area under the curve (AUC) comparisons were performed using the DeLong test. Results:The differences in tumor bladder wall contact length, perpendicular distance from the tumor to the tangent line of the bladder wall, maximum diameter, bladder tumor volume, and the VI-RADS scores were statistically significant between the MIBC group and the NMIBC group ( P<0.05). Multifactorial logistic regression analysis showed that tumor bladder wall contact length ( OR=21.07, 95% CI 3.56-124.89, P=0.001) and VI-RADS score ( OR=11.90, 95% CI 3.53-40.12, P<0.001) were the independent risk factors for evaluating the muscle invasion of bladder cancer. The difference between the VI-RADS score and the tumor bladder wall contact length for assessing muscular infiltration of bladder cancer had AUCs of 0.802 (95% CI 0.704-0.899) and 0.759 (95% CI 0.652-0.865). The combined model of VI-RADS score combined with tumor bladder wall contact length had an AUC of 0.891 (95% CI 0.812-0.970), which was higher than the diagnostic efficacy of applying tumor bladder wall contact length or VI-RADS score alone ( Z=3.05, 2.37, P=0.002, 0.018). Conclusion:Tumor contact length with the bladder wall is an independent risk factor for assessing muscle invasion of bladder cancer and the combination of VI-RADS score may enhances diagnostic accuracy.

Objective To identify the multi-dimensional needs of symptom management for oral cancer patients based on the journey map,and provide references for optimizing the symptom management of oral cancer patients.Methods From September 2023 to March 2024,the purposive sampling was used to select 15 perioperative oral cancer patients from a tertiary A general hospital in Zhengzhou for semi-structured interviews.The content analysis method was used to analyze the data and create a patient journey map.Results According to the time axis of diagnosis and treatment,the symptom management of patients with oral cancer was subdivided into 22 themes including identifying abnormal symptoms,clarifying diagnosis,anxiety,fear and uncertainty,guilt,high-risk behavioral inertia solidification,diagnostic trust crisis and so on from 3 dimensions of task,emotion,and pain point,and a journey map was formed.Conclusion The journey of symptom management for patients with oral cancer is long and complex,and the needs of patients'physiological and psychological symptom management are dynamically changing.In the future,the digital intelligence of big data technology can be combined to achieve whole-process,personalized and precise symptom management to improve the quality of life of oral cancer patients.

OBJECTIVE To investigate the distribution and drug resistance of multidrug-resistant bacteria in the neonatal intensive care unit of a three-A children's hospital in Henan Province,and to provide reference for ational drug use in clinical practice.METHODS Clinical specimens from hospitalized newborns in neonatal intensive care unit from a three-A children's hospital from Jan.1,2019 to Dec.31,2023 were subjected to etiological exam-ination and drug sensitivity test,and to analyze the distribution and drug resistance of multidrug-resistant bacteri-a in hospitalized newborns.RESULTS During the 5-year period,1139 strains of multidrug-resistant bacteria were i-solated,including 229 gram-positive bacteria(20.11％)and 910 gram-negative bacteria(79.89％).There were 92 strains of methicillin-resistant Staphylococcus aureus(MRSA)(accounting for 8.08％),57 strains(accounting for 5.00％)of methicillin-resistant coagulase-negative Staphylococcus epidermidis and 28 strains(accounting for 2.46％)of methicillin-resistant coagulase-negative human Staphylococcus.370 strains(accounting for 32.48)of carbapenem-resistant Klebsiella pneumoniae(CRKP),268 strains(accounting for 23.53％)of extenspectrum β-lactamase-producing Escherichia coli and 85 strains(accounting for 7.46％)of K.pneumoniae,there were 767 sputum specimens(67.34％),160 blood specimens from peripheral intravenous puncture and central venous cath-eterization(PICC)(14.05％),63 bronchoalveolar lavage fluid specimens(5.53％),29 secretion specimens(eye and wound secretions)(2.54％),and 120 other specimens(10.54％).K.pneumoniae and E.coli producing su-per-broad spectrum β-lactamase,CRKP and MRSA were the main drug-resistant bacteria.CONCLUSION The sit-uation of drug resistance in neonatal intensive care unit is serious,therefore monitoring bacterial resistance should be strengthened according to the clinical laboratory results,and antibiotics should be applied rationally.

Objective:To explore the current therapeutic status of rhythm control versus rate control in elderly patients with atrial fibrillation(AF)and the related factors that may influence treatment decisions.Methods:A retrospective study was conducted on AF patients aged ≥75 years old who were hospitalized in the Healthcare Department of Beijing Hospital from January 2010 to May 2020.The patients were grouped and compared according to whether they underwent rhythm control or rate control.Multivariate logistic regression analysis was used to investigate the factors that may influence the treatment decision of rhythm control or rate control.Results:A total of 167 patients was included, with a median age of 90 years old.Among them, 21 patients(12.6%)received rhythm control, and 109 patients(65.3%)received rate control.Compared with the group not receiving rhythm control, the rhythm control group had a younger age, higher BMI, higher diastolic blood pressure, a higher proportion of multiple medication use, a lower proportion of chronic kidney disease stage 3 or above, and higher hemoglobin levels(all P<0.05). Compared with the group not receiving rate control, the rate control group had a lower proportion of paroxysmal AF, a faster resting ventricular rate, a higher proportion of smoking history, a higher proportion of multiple medication use, coronary heart disease, pacemaker treatment, chronic obstructive pulmonary disease and/or asthma, and a lower proportion of cognitive impairment(all P<0.05). Multivariate logistic regression analysis revealed that multiple drug use( OR=11.578, 95% CI: 1.341-99.993, P=0.026)was positively associated with rhythm control therapy, while chronic kidney disease stage 3 or above( OR=0.248, 95% CI: 0.063-0.968, P=0.045)was negatively associated with rhythm control therapy.For rate control therapy, multiple drug use( OR=5.056, 95% CI: 2.253-11.347, P<0.001), resting ventricular rate( OR =1.033, 95% CI: 1.005-1.062, P=0.021), and chronic obstructive pulmonary disease(COPD)and/or asthma( OR=2.739, 95% CI: 1.124-6.672, P=0.027)showed positive associations. Conclusions:The application rate of rhythm control therapy is low in elderly AF patients, and ventricular rate control is the main treatment.Complex clinical conditions are the main constraints, and it is urgent to optimize individualized strategies based on prospective studies and develop new treatment techniques to improve clinical practice.