Cyclin-dependent kinase(CDK)4/6 inhibitors plus endocrine therapy represents the standard first-line treatment for patients with hormone receptor-positive,human epidermal growth factor receptor 2(HER2)-negative advanced breast cancer.The introduction of CDK4/6 inhibitors has significantly improved the prognosis of breast cancer patients.However,it has also brought new clinical challenges,such as disease progression and treatment resistance in many patients.Currently,there is a lack of standardized subsequent treatment options for patients whose disease progresses after CDK4/6 inhibitor combined with endocrine therapy.Endocrine therapy resistance can lead to tumor progression through estrogen receptor(ESR)-dependent or ESR-independent pathways.Novel endocrine agents have the potential to benefit breast cancer patients harboring ESR1 mutations.Patients with alterations in the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway may be particularly sensitive to targeted inhibitors of this pathway.Furthermore,newly approved or investigational antibody-drug conjugate(ADC),immunotherapy-based combinations,and novel cell cycle inhibitors have demonstrated promising anti-tumor activities.Precision medicine-based combination strategies not only expand clinical treatment options but also enable physicians to make personalized treatment decisions for patients.Biomarker-driven precision therapeutic strategies have emerged as a critical area of treatment development in the post-CDK4/6 inhibitor era.

Objective:To explore the current dietary patterns and influencing factors of patients with coronary heart disease (CHD) in severe cold regions, aiming to provide scientific evidence for developing targeted dietary interventions.Methods:A total of 340 patients with CHD who visited the Department of Cardiology at the Second Affiliated Hospital of Harbin Medical University between September and December 2023 were selected using convenience sampling. Patients were assessed using a general information questionnaire, Semi-Quantitative Food Frequency Questionnaire, Food Choice Questionnaire, Nutritional Knowledge Questionnaire, 7-Item Generalized Anxiety Disorder Scale, and Patient Health Questionnaire-9.Results:A total of 340 questionnaires were distributed, and 333 valid questionnaires were collected, with an effective response rate of 97.94% (333/340). Two dietary patterns were identified among patients with CHD in severe cold regions: a "fruit-nut-dairy" dietary pattern and a "meat-seafood-grain" dietary pattern. Factors influencing the "fruit-nut-dairy" dietary pattern included gender, nutritional knowledge, and food choice motivations such as accessibility, sensory appeal, brand and packaging, and emotional dimensions ( P<0.05). Factors influencing the "meat-seafood-grain" dietary pattern included body mass index (BMI), living alone or not, monthly income, and food choice motivations such as convenience, health attributes, sensory appeal, and price ( P<0.05) . Conclusions:When providing dietary interventions for CHD patients, targeted control of factors such as gender, BMI, living alone or not, monthly income, nutritional knowledge, and key elements of food choice motivations may optimize patients' irrational dietary structures and reduce adverse disease outcomes.

Cyclin-dependent kinase(CDK)4/6 inhibitors plus endocrine therapy represents the standard first-line treatment for patients with hormone receptor-positive,human epidermal growth factor receptor 2(HER2)-negative advanced breast cancer.The introduction of CDK4/6 inhibitors has significantly improved the prognosis of breast cancer patients.However,it has also brought new clinical challenges,such as disease progression and treatment resistance in many patients.Currently,there is a lack of standardized subsequent treatment options for patients whose disease progresses after CDK4/6 inhibitor combined with endocrine therapy.Endocrine therapy resistance can lead to tumor progression through estrogen receptor(ESR)-dependent or ESR-independent pathways.Novel endocrine agents have the potential to benefit breast cancer patients harboring ESR1 mutations.Patients with alterations in the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway may be particularly sensitive to targeted inhibitors of this pathway.Furthermore,newly approved or investigational antibody-drug conjugate(ADC),immunotherapy-based combinations,and novel cell cycle inhibitors have demonstrated promising anti-tumor activities.Precision medicine-based combination strategies not only expand clinical treatment options but also enable physicians to make personalized treatment decisions for patients.Biomarker-driven precision therapeutic strategies have emerged as a critical area of treatment development in the post-CDK4/6 inhibitor era.

Objective:To explore the current dietary patterns and influencing factors of patients with coronary heart disease (CHD) in severe cold regions, aiming to provide scientific evidence for developing targeted dietary interventions.Methods:A total of 340 patients with CHD who visited the Department of Cardiology at the Second Affiliated Hospital of Harbin Medical University between September and December 2023 were selected using convenience sampling. Patients were assessed using a general information questionnaire, Semi-Quantitative Food Frequency Questionnaire, Food Choice Questionnaire, Nutritional Knowledge Questionnaire, 7-Item Generalized Anxiety Disorder Scale, and Patient Health Questionnaire-9.Results:A total of 340 questionnaires were distributed, and 333 valid questionnaires were collected, with an effective response rate of 97.94% (333/340). Two dietary patterns were identified among patients with CHD in severe cold regions: a "fruit-nut-dairy" dietary pattern and a "meat-seafood-grain" dietary pattern. Factors influencing the "fruit-nut-dairy" dietary pattern included gender, nutritional knowledge, and food choice motivations such as accessibility, sensory appeal, brand and packaging, and emotional dimensions ( P<0.05). Factors influencing the "meat-seafood-grain" dietary pattern included body mass index (BMI), living alone or not, monthly income, and food choice motivations such as convenience, health attributes, sensory appeal, and price ( P<0.05) . Conclusions:When providing dietary interventions for CHD patients, targeted control of factors such as gender, BMI, living alone or not, monthly income, nutritional knowledge, and key elements of food choice motivations may optimize patients' irrational dietary structures and reduce adverse disease outcomes.

OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective:To compare the teaching effect of basic medical integrated courses and clinical medical integrated courses based on organ system with the traditional teaching model based on discipline,so as to provide theoretical reference for training medical talents.Methods:The program of integration of basic medical courses and clinical medical courses was formulated.The current clinical medical students who participated in the medical licensing examination were selected as the research objects under the three teaching models of basic and clinical medical integrated courses,clinical medical integrated courses,and discipline-based courses.The students'scores of comprehensive basic medicine,comprehensive clinical medicine,and medical licensing examination were analyzed to preliminarily evaluate the implementation effect of the integrated teaching model of basic medicine and clinical medicine.Result:There was no significant difference in the examination scores of students under the three teaching modes.Conclusion:The organ system-based integrated teaching model has no significant effect on students'academic performance in the short term.

Early screening for neonatal jaundice has always been essential to neonatal health care. In recent years, there have been advancements and updates in the methods and equipment employed for early screening of neonatal jaundice, including visual assessment, icterometer, point-of-care testing of serum bilirubin, jaundice screening utilizing smartphone applications, and end-tidal carbon monoxide detection. This article reviews the relevant research and progress associated with the methods above, aiming to offer a reference and guidance for scientific research and clinical practices.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.