Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective To investigate the risk factors for postoperative anastomotic stenosis in esophageal cancer patients.Methods A total of 200 patients who underwent radical esophageal cancer resection at the First Affiliated Hospital of Dali University from July 2015 to June 2024 were selected as subjects.The patients were divided into stenosis group(n=100)and non-stenosis group(n=100)based on whether they had benign anastomotic stenosis.Comparative analyses were conducted regarding the first feeding time,surgical duration,use of non-linear anastomotic devices,and anastomotic leakage in both groups.The independent risk factors for benign postoperative anastomotic stenosis were systematically evaluated.Results Delayed initial postoperative feeding,non-linear anastomotic devices,anastomotic leakage,and persistent postoperative hypoxemia were identified as risk factors for anastomotic stenosis in esophageal cancer patients after neck anastomosis.Balloon dilation-induced bleeding and early postoperative feeding within 12h served as protective factors(P＜0.05).Conclusion The development of anastomotic stenosis in esophageal cancer patients following neck anastomosis may be associated with delayed initial feeding,non-linear anastomotic devices,anastomotic leakage,and persistent hypoxemia.

A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

Objective:To summarize the best evidence on palliative care for end-stage heart failure patients, so as to provide ideas and references for clinical healthcare professionals and decision-makers.Methods:According to the "6S" evidence pyramid model, clinical decisions, guidelines, expert consensus, and systematic reviews on palliative care for patients with end-stage heart failure were searched from top to bottom in BMJ Best Practice, UpToDate, Joanna Briggs Institute (JBI) Evidence-Based Health Care Center Database, Guidelines International Network, National Guideline Clearinghouse, PubMed, Web of Science, China National Knowledge Infrastructure, WanFang Data, SinoMed, VIP, and other websites and databases. Two researchers evaluated the quality of the literature and extracted information.Results:A total of 15 papers were included, including 4 guidelines, 2 clinical decisions, 7 expert consensus, and 2 randomized controlled trials. Twenty-four pieces of best evidence were developed from 11 aspects of goals, place, team building and training, applicability, key components, assessment, communication and shared decision-making, quality of life improvement, symptom management, psychological and spiritual care, and hospice care.Conclusions:The summarized best evidence on palliative care for patients with end-stage heart failure is scientific and standardized, and can guide healthcare professionals to use the evidence in a targeted way that takes into account the patient's condition and wishes to improve the patient's quality of life.

Objective:To investigate the role of hypoxia-induced angiopoietin-like protein 4 (ANGPTL4) expression in experimental choroidal neovascularization (CNV).Methods:Twenty-seven SPF male C57BL/6J mice aged 6-8 weeks were selected.Eighteen of the mice were used to establish a laser-induced CNV model.On the 7th day after laser photocoagulation, success of the modeling was verified using optical coherence tomography angiography (OCTA) and fundus fluorescein angiography (FFA). The retinal pigment epithelium (RPE)-choroid-sclera complex was extracted for protein analysis before modeling and on the 3rd and 7th days after modeling.The relative expression levels of ANGPTL4 and vascular endothelial growth factor (VEGF) at different time points were detected by Western blot.Additionally, frozen sections of mouse eyeballs on day 7 after modeling were prepared and the expression and cellular localization of ANGPTL4 were observed by immunofluorescence.RF/6A cells, derived from monkey choroidal retinal endothelial cells, were treated with 200 μmol/L cobalt chloride (CoCl 2) in the culture medium for 0, 3, 6, and 12 hours.RF/6A cells were also divided into a normal control group, a hypoxia group, and a hypoxia+ si-ANGPTL4 group, and cells were transfected with a plasmid containing si-ANGPTL4 sequence.The relative expression levels of ANGPTL4 and VEGF proteins in each group were detected by Western blot, and the differences in tube formation among the groups were observed by tube formation assay.A total of 27 male C57BL/6J mice were randomly divided into CNV group, CNV+ si-NC group, and CNV+ si-ANGPTL4 group, with 9 mice in each group.In the CNV+ si-NC and CNV+ si-ANGPTL4 groups, si-NC and si-ANGPTL4 were respectively injected into the vitreous cavity after the CNV model was established.Fluorescence leakage in mice was observed by FFA, and the length, thickness and area of CNV was observed using OCTA and immunofluorescence staining of choroidal flat mounts.The relative expression levels of ANGPTL4 and VEGF proteins in each group were detected by Western blot.All animal experiments were conducted in accordance with ARVO Statement on the Use of Animals in Ophthalmic and Vision Research.The experimental protocol was approved by the Affiliated Hospital of Nantong University (No.S20220822-902). Results:Before modeling and on the 3rd and 7th days after modeling, the relative expression levels of ANGPTL4 protein were 1.00±0.00, 1.58±0.05, and 1.90±0.04, respectively, and the relative expression levels of VEGF protein were 1.00±0.00, 1.31±0.05, and 1.84±0.04, respectively, with statistically significant overall differences ( F=528.934, 390.424, both P<0.05). Among them, on the 3rd and 7th days after modeling, the relative expression levels of ANGPTL4 and VEGF proteins were significantly higher in CNV group than in the control group (all P<0.05). The tissues of each layer of the retina were clear in the control group, while neovascularization could be seen growing under the retinal neuroepithelial layer in the CNV group.Compared with the control group, ANGPTL4 expression was significantly increased and colocalized with vascular endothelial cells in the CNV group.After CoCl 2 treatment of RF/6A cells for 3, 6, and 12 hours, the relative expression levels of ANGPTL4 and VEGF proteins were higher than at 0 hour, with statistically significant differences (all P<0.05). Compared with the control group, the relative ANGPTL4 protein expression was increased in the hypoxia group and significantly decreased in the hypoxia+ si-ANGPTL4 group, showing statistically significant differences (both P<0.05). The number of tube formations in the control group, hypoxia group, and hypoxia+ si-ANGPTL4 group were 12.67±1.53, 19.64±1.56, and 17.01±1.04, respectively, with a statistically significant overall difference ( F=33.091, P<0.01). The number of tube formations increased in the hypoxia group and hypoxia+ si-ANGPTL4 group compared with the control group, and the number of tube formations decreased in the hypoxia+ si-ANGPTL4 group compared with the hypoxia group, with statistically significant differences (all P<0.05). Relative expression levels of ANGPTL4 and VEGF proteins were significantly lower in the CNV+ si-ANGPTL4 group than those in the CNV group (both P<0.05). The CNV area was significantly lower in the CNV+ si-ANGPTL4 group than in the CNV group and CNV+ si-NC group (both P<0.05). Conclusions:Hypoxia-induced ANGPTL4 promotes experimental CNV formation in vivo and in vitro.Inhibiting ANGPTL4 can reduce CNV formation and leakage.

Objective:The clinical symptoms of children with global developmental delay (GDD) were analyzed to provide the scientific basis for the intervention of children with GDD.Methods:The results of the neuro-psychobehavioral scale were collected from 32 511 children with GDD from June 2020 to November 2023. Inclusion criteria: Children diagnosed with GDD according to the Diagnostic and Statistical Manual of Mental Disorders-V, ages 0.0 to 4.9 years. Exclusion criteria: children with common hearing impairment and visual impairment. The Chi-square tests were used for statistical analysis.Results:There were more boys than girls with GDD in outpatient clinics (68.2% vs. 31.8%). Among the children, the proportion of developmental delay in 5, 4, 3, and 2 domains was 31.1%, 23.4%, 22.9% and 22.6% respectively. The rate of delay in 2-3 domains was lower in boys (41.9%) than in girls (53.1%). The rate of delay in 4-5 domains was higher in boys (58.1%) than in girls (46.9%) ( χ2=352.11, P<0.001). Overall, outpatient GDD decreased with age. From 1.0-1.9 to 4.0-4.9 years of age, the proportion of children with developmental delay in 5 domains increased with age (18.2%, 36.4%, 43.9%, 52.4%). Among children aged 0.0-0.9 years, the proportion of 2 domains of developmental delay was higher (33.4%).Among children aged 1.0-1.9 years, the proportion of 2-3 domains of developmental delay was higher (30.7%). Among children aged 2.0-, 3.0-, 4.0-4.9 years, the proportion of developmental delay in 5 domains was higher (36.4%, 43.9%, 52.4%). In children with GDD, the fine motor delay occurred most frequently (85.1%), followed by social self-care (83.9%), language (79.0%), adaptation (62.3%), and gross motor (52.8%). The frequency of developmental delays in fine motor, adaptability, language, and social self-care in boys was higher than that in girls ( χ2=161.37, χ2=41.10, χ2=320.90, χ2=238.54, all P<0.001). The age groups with the highest delay incidence of gross motor, fine motor, adaptability, language, and social self-care were: 4.0-4.9 years (70.6%), 3.0-3.9 years (97.4%), 4.0-4.9 years (81.2%), 2.0-2.9 years (90.9%),2.0-2.9 years (95.4%). The proportions of fine motor delay in GDD children aged 0.0-0.9, 3.0-3.9 and 4.0-4.9 years were (74.5%, 97.4%, 96.8%) and the proportions of social self-care delay in GDD children aged 1.0- and 2.0-2.9 years were (92.1%, 95.4%). Peripheral and mild developmental delays were predominant in children with GDD. The proportion of severe language delay (6.4%) was higher than that in other fields. Conclusions:The proportion of GDD children with developmental delay in 4-5 domains was 54.5%. The most frequent domain of delay was fine motor. The frequencies of developmental delays in fine motor skills, adaptability, language, and social self-care in boys were higher than in girls. Most of the developmental delays in GDD children were marginal and mild. The rate of severe developmental delay in language was higher than in other domains.

Objective:To analyze the key β-amyloid protein (Aβ) deposition in brain regions affecting the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD).Methods:Based on the positron emission tomography data of Aβ in the Alzheimer's disease neuroimaging initiative database, the penalized generalized estimating equation (PGEE) and the mixed effects regression forest algorithm (MERF) were used to conduct dimensionality reduction analysis on 164 brain regions with Aβ deposition. Additionally, a multivariate longitudinal data joint model was used to screen the key Aβ deposition brain regions that influence the progression from MCI to AD.Results:Five key brain regions were commonly screened out by the PGEE and MERF models, they were the right prefrontal orbital cortex, the left superior temporal sulcus shore cortex, the right medial orbitofrontal cortex, the left putamen, and the right transverse temporal cortex, respectively. The results of the multivariate longitudinal data joint model based on these 5 Aβ deposition brain regions showed that, except the left superior temporal sulcus shore cortex, the longitudinal change trajectories of the other 4 Aβ deposition brain regions all affected the progression from MCI to AD ( P<0.05). Conclusion:The Aβ deposition in the right prefrontal orbital cortex, right medial orbitofrontal cortex, left putamen and right transverse temporal cortex affect the progression from MCI to AD.

Objective To explore the clinical value of mini-incision combined with balloon dilatation under the guidance of miniprobe echoendoscope in the treatment of refractory benign esophageal stenosis.Methods From October 2019 to October 2023,30 cases of esophageal early cancer with esophageal scar stenosis after endoscopic submucosal dissection(ESD)were selected and randomly divided into study group(miniprobe echoendoscope guided small incision+balloon dilatation,15 cases)and control group[esophageal radial incision(ERI),15 cases],EUS in the study group judged the hierarchical structure of esophageal wall before operation,and excluded those with esophageal cancer recurrence and submucosal invasive growth.According to miniprobe echoendoscope,the length of scar segment and the scope of scar ring lumen were defined,and the location and length of pre-incision were defined,and then balloon was used to expand step by step.The short-term postoperative complications,Stooler dysphagia scale score and restenosis rate of the two groups were observed,and the feasibility,safety and efficacy were evaluated.Results The incidence of short-term postoperative complications 6.7％in the study group was significantly lower than that 46.7％in the control group,the difference was statistically significant(P＜0.05),and the Stooler dysphagia scale score were(1.133±0.990)and(1.600±0.737)in the study group at 1 and 2 months after operation with significantly lower than those(2.067±1.033)and(2.467±0.915)in the control group,the differences were statistically significant(P＜0.05).Two months after operation,the restenosis rate was 13.3％,which was significantly lower than that 46.7％of the control group,the difference was statistically significant(P＜0.05),and the scar thickness under miniprobe echoendoscope(2.113±0.887)mm was significantly thinner than that(3.353±1.468)mm of the control group,the difference was statistically significant(P＜0.05).Conclusion Preoperative miniprobe echoendoscope evaluation,can accurately locate lesions,endoscopic mini-incision combined with balloon mechanical expansion are safe and effective,with less pain and fewer postoperative complication.

Objective To clarify the concept of caregiver fatigue in an aging society and to provide references in the elderly people nursing.Methods Literature on caregiver fatigue was systematically retrieved from databases of China National Knowledge Infrastructure(CNKI),Wanfang Data,Chinese Biomedical Literature Database,PubMed,EMbase,Scopus,and Web of Science from the inception to June 15th 2024.Walker and Avant's framework for concept analysis was performed to analyse the retrieved literature.Results Forty-one papers were included in the study.Caregiver fatigue was identified to comprise of five defining attributes:simultaneous physical and psychological burden,subjective perception,changing over time,negative impact arising from caregiving,and negative impact on both caregivers and care recipients.Antecedents included three perspectives:caregiver-related,care-recipient-related and environmental,The consequences included an impact on both the caregiver and the person being cared for.Empirical assessment indicators of fatigue include the checklist individual strength(CIS)and the fatigue assessment instrument(FAI)and fatigue scale-14(FS-14,FS-14).Conclusion Walker and Avant's conceptual analysis identifies five attributes of caregiver fatigue.Nurses should pay attention to and evaluate the degree of caregiver fatigue from multiple perspectives,thereby effectively identifying and intervening in the fatigue as early as possible.

Objective:To investigate the neuroprotective effect of vanillin on experimental autoimmune encephalomyelitis(EAE)rats by regulating C-X-C motif chemokine ligand 12(CXCL12)/chemokine(C-X-C motif)receptor(CXCR4)signaling path-way.Methods:A total of 50 rats were injected with 400 μl guinea pig spinal cord and water in oil mixture of complete Freund's adju-vant to establish EAE rat model,and were divided into model group,low-dose vanillin group(50 mg/kg),medium-dose vanillin group(100 mg/kg),high-dose vanillin group(200 mg/kg)and positive drug group(5 mg/kg prednisone acetate),another 10 rats were only injected with the mixture of the same amount of normal saline and complete Freud adjuvant as control group,since the first day of mod-eling,all rats were given corresponding drugs by gavage for 16 consecutive days,and after modeling,rats in each group were scored for neurological function every day;HE and LFB staining were used to observe the pathology and demyelination of spinal cord in rats;levels of serum TNF-α,IL-1β and IL-6 were detected by ELISA;immunohistochemistry was used to detect expressions of CD68 and Iba-1 in spinal cord of rats;Western blot was used to detect expressions of CXCL12 and CXCR4 proteins in spinal cord of rats.Results:Compared with control group,rats in model group showed obvious infiltration of inflammatory cells,a large number of inflammatory cells gathered around the small blood vessels,and the structure of myelin sheath in spinal cord of rats was abnormal,accompanied by a large number of myelin sheath loss,the neurological function score,inflammatory infiltration score and demyelination score of spinal cord,serum TNF-α,IL-1β and IL-6 levels,spinal cord CD68 and Iba-1 proteins,CXCL12 and CXCR4 proteins expressions in-creased obviously(P<0.05);compared with model group,inflammatory cell infiltration and myelin sheath loss of rats in low,medium and high doses groups and positive drug group were obviously alleviated,neurological function score,inflammatory infiltration score and demyelination score of spinal cord,serum TNF-α,IL-1β and IL-6 levels,and expressions of CD68 and Iba-1 proteins in spinal cord decreased obviously(P<0.05),while expressions of CXCL12 and CXCR4 proteins in spinal cord further increased(P<0.05).Conclusion:Vanillin inhibits inflammatory response and alleviates nerve injury in EAE rats,and its mechanism may be related to acti-vation of CXCL12/CXCR4 signaling pathway.