Objective To explore the characteristics of latent profiles of ego depletion in patients with heart failure,and analyze the impacts of these profiles on patients' self-management behavior.Methods 280 heart failure patients who were hospitalized in a tertiary grade A hospital were conveniently selected in Nanjing from April to October 2024 as study subjects.The investigation utilized a general information questionnaire,the Ego-Depletion Scale for Heart Failure Patients,the Self-Management Scale of Heart Failure Patients,and the Chronic Disease Self-Efficacy Scale.The latent profile categories of ego depletion was explored in heart failure patients.Univariate analysis and multiple Logistic regression analysis were used to investigate the influencing factors of different latent profile categories and the impact of each category on patients' self-management levels.Results The ego depletion of 255 heart failure patients could be classified into 3 latent profiles:self-adaptive low depletion group(35.29％),symptom distressed moderate depletion group(43.53％),and social life change high depletion group(21.18％).Multiple Logistic regression analysis showed that residence,primary caregiver,education level,New York Heart Association cardiac function grade,and self-efficacy score were factors influencing the potential profile of ego depletion in heart failure patients(P＜0.05).The comparison of self-management scores among patients in different latent profiles of ego depletion showed statistically significant differences(P＜0.05).Conclusion The level of ego depletion in patients with heart failure is high with significant heterogeneity.Medical staff should pay attention to the heterogeneity and influencing factors of ego depletion in patients with heart failure in time,and develop personalized comprehensive intervention strategies to alleviate ego depletion and improve their self-management levels.

BACKGROUND:It is urgent to improve the study on the molecular mechanism of Ban's Culuan Zhuyun Decoction improving oocyte quality in polycystic ovary syndrome.OBJECTIVE:To observe the effects of Ban's Culuan Zhuyun Decoction on oocyte quality in a mouse model of polycystic ovary syndrome and to explore the underlying mechanisms of its intervention in polycystic ovary syndrome.METHODS:Subcutaneous injection of dehydroepiandrosterone sulfate was used to establish the polycystic ovary syndrome model in 21-day-old female Kunming mice,and the treatment was conducted for 21 consecutive days.The estrous cycle and pregnancy was recorded.ELISA was used to detect serum sex hormone levels.The rate of apoptosis in oocytes was detected using Annexin V staining.The level of reactive oxygen species in oocytes was detected using dichlorodihydrofluorescein diacetate.The condition of spindle bodies and chromosomes in oocytes were detected using the immunofluorescence method.Network pharmacology and molecular docking were used to verify the binding properties of Ban's Culuan Zhuyun Decoction core active components and oocyte maturation-related factors(growth differentiation factor 9 and bone morphogenetic protein 15).Real-time fluorescence quantitative PCR and western blot were used to detect the mRNA and protein expression levels of growth differentiation factor 9 and bone morphogenetic protein 15 in oocytes,respectively.RESULTS AND CONCLUSION:(1)Ban's Culuan Zhuyun Decoction core active components(quercetin,kaempferol,and β-sitosterol)showed good binding activities with growth differentiation factor 9 and bone morphogenetic protein 15.(2)Ban's Culuan Zhuyun Decoction ameliorated the estrous cycle,regulated serum hormone,increased the pregnancy,decreased the rate of apoptosis,declined the level of reactive oxygen species,diminished the rate of abnormal spindle assembly and chromosome loss(P<0.01,P<0.05);and promoted the mRNA and protein expression of growth differentiation factor 9 and bone morphogenetic protein 15(P<0.05).Therefore,Ban's Culuan Zhuyun Decoction may improve the oocyte quality and increase the fertility of polycystic ovary syndrome mice by regulating the gene expression of growth differentiation factor 9 and bone morphogenetic protein 15.

BACKGROUND:It is urgent to improve the study on the molecular mechanism of Ban's Culuan Zhuyun Decoction improving oocyte quality in polycystic ovary syndrome.OBJECTIVE:To observe the effects of Ban's Culuan Zhuyun Decoction on oocyte quality in a mouse model of polycystic ovary syndrome and to explore the underlying mechanisms of its intervention in polycystic ovary syndrome.METHODS:Subcutaneous injection of dehydroepiandrosterone sulfate was used to establish the polycystic ovary syndrome model in 21-day-old female Kunming mice,and the treatment was conducted for 21 consecutive days.The estrous cycle and pregnancy was recorded.ELISA was used to detect serum sex hormone levels.The rate of apoptosis in oocytes was detected using Annexin V staining.The level of reactive oxygen species in oocytes was detected using dichlorodihydrofluorescein diacetate.The condition of spindle bodies and chromosomes in oocytes were detected using the immunofluorescence method.Network pharmacology and molecular docking were used to verify the binding properties of Ban's Culuan Zhuyun Decoction core active components and oocyte maturation-related factors(growth differentiation factor 9 and bone morphogenetic protein 15).Real-time fluorescence quantitative PCR and western blot were used to detect the mRNA and protein expression levels of growth differentiation factor 9 and bone morphogenetic protein 15 in oocytes,respectively.RESULTS AND CONCLUSION:(1)Ban's Culuan Zhuyun Decoction core active components(quercetin,kaempferol,and β-sitosterol)showed good binding activities with growth differentiation factor 9 and bone morphogenetic protein 15.(2)Ban's Culuan Zhuyun Decoction ameliorated the estrous cycle,regulated serum hormone,increased the pregnancy,decreased the rate of apoptosis,declined the level of reactive oxygen species,diminished the rate of abnormal spindle assembly and chromosome loss(P<0.01,P<0.05);and promoted the mRNA and protein expression of growth differentiation factor 9 and bone morphogenetic protein 15(P<0.05).Therefore,Ban's Culuan Zhuyun Decoction may improve the oocyte quality and increase the fertility of polycystic ovary syndrome mice by regulating the gene expression of growth differentiation factor 9 and bone morphogenetic protein 15.

Objective To explore the characteristics of latent profiles of ego depletion in patients with heart failure,and analyze the impacts of these profiles on patients' self-management behavior.Methods 280 heart failure patients who were hospitalized in a tertiary grade A hospital were conveniently selected in Nanjing from April to October 2024 as study subjects.The investigation utilized a general information questionnaire,the Ego-Depletion Scale for Heart Failure Patients,the Self-Management Scale of Heart Failure Patients,and the Chronic Disease Self-Efficacy Scale.The latent profile categories of ego depletion was explored in heart failure patients.Univariate analysis and multiple Logistic regression analysis were used to investigate the influencing factors of different latent profile categories and the impact of each category on patients' self-management levels.Results The ego depletion of 255 heart failure patients could be classified into 3 latent profiles:self-adaptive low depletion group(35.29％),symptom distressed moderate depletion group(43.53％),and social life change high depletion group(21.18％).Multiple Logistic regression analysis showed that residence,primary caregiver,education level,New York Heart Association cardiac function grade,and self-efficacy score were factors influencing the potential profile of ego depletion in heart failure patients(P＜0.05).The comparison of self-management scores among patients in different latent profiles of ego depletion showed statistically significant differences(P＜0.05).Conclusion The level of ego depletion in patients with heart failure is high with significant heterogeneity.Medical staff should pay attention to the heterogeneity and influencing factors of ego depletion in patients with heart failure in time,and develop personalized comprehensive intervention strategies to alleviate ego depletion and improve their self-management levels.

The new generation of artificial intelligence technology,represented by deep learning,has emerged as a crucial driving force in the advancement of new drug research and development.This article creatively proposes a workflow named"Molecular Factory"for the design and optimization of drug molecules based on artificial intelligence technology.This workflow integrates intelligent molecular generation models,high-performance molecular docking algorithms,and accurate protein-ligand binding affinity prediction methods.It has been integrated as a core module into DrugFlow,a one-stop drug design software platform,providing a comprehensive set of mature solutions for the discovery and optimization of lead compounds.Utilizing the"Molecular Factory"module,we conducted the research of second-generation inhibitors against Menin that can combat drug resistance.Through the integration of computational and experimental approaches,we rapidly identified multiple promising compounds.Among them,compound RG-10 exhibited the IC50 values of 9.681 nmol/L,233.2 nmol/L,and 40.09 nmol/L against the wild-type Menin,M327I mutant,and T349M mutant,respectively.Compared to the positive reference molecule SNDX-5613,which has entered Phase Ⅱ clinical trials,RG-10 demonstrated significantly enhanced inhibitory activity against the M327I and T349M mutants.These findings fully demonstrate the unique advantages of the"Molecular Factory"technology in practical drug design and development scenarios.It can rapidly and efficiently generate high-quality active molecules targeting specific protein structures,holding significant value and profound implications for advancing new drug discovery.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective To understand the epidemic characteristics of heart failure in Guangzhou, and to provide a basis for the prevention and control of heart failure. Methods The information of patients hospitalized for heart failure in Guangzhou from January 1, 2017 to December 31, 2021 was collected, and t test, rank sum test, and χ² test were used to analyze the differences of central tendency and composition ratio. Results From 2017 to 2021, there were 6 823 hospitalized patients with heart failure in Guangzhou, with 8,716 hospitalizations and 849 deaths. The average age of hospitalization was 78.50 ±10.48 years old. Male patients were younger than female patients (P<0.001), and females died 3.86 years later than males on average (P<0.001). The number of hospitalizations for males (4 251 person times, accounting for 48.77%) was less than that for females (4 465 person times, accounting for 51.23%), and the number of hospitalizations for urban registered residence (7 346 person times, accounting for 84.28%) was much more than that for rural registered residence (1 370 person times, accounting for 15.72%). The number of hospitalizations in the fourth quarter was the largest. The combined rates of coronary heart disease, hypertension, type 2 diabetes, chronic obstructive pulmonary disease and hyperlipidemia were 58.65%, 69.52%, 34.92%, 10.69% and 10.23% respectively. There were differences in age, registered residence, residential area and complications among patients with acute and chronic heart failure (P<0.05). Conclusion The mortality of patients with heart failure in Guangzhou is high, and the distribution characteristics of acute and chronic heart failure is different. Corresponding preventive measures should be taken for different groups to reduce the disease burden and improve the quality of life.

Objective:To evaluate the prognostic value of pretreatment systemic immune-inflammation index (SII) and lactate dehydrogenase (LDH) in non-metastatic nasopharyngeal carcinoma (NPC).Methods:We retrospectively collected the data of 839 patients with non-metastatic NPC from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Sun Yat-sen University Cancer Center between January 2007 and October 2015. All patients received intensity modulated radiation based treatment. Optimal cutoff value of SII and LDH were determined by X-title software. The association between SII, LDH and clinical prognosis of non-metastatic NPC patients were analyzed. Kaplan-Meier method was used for survival analysis, and Log rank test was used for comparison of survival rates between groups. Propensity score matching (PSM) analysis was carried out to minimize the effects of confounding factors. The risk stratification model of prognosis by combining N stage, SII and LDH was constructed to compare the prognosis of patients in high risk group, middle risk group and low risk group, and the receiver operating characteristic (ROC) curve analysis was used to evaluate its prognostic value.Results:The optimal cutoff value of SII is 447.2×10 9/L for predicting the 5-year overall survival (OS) of NPC patients, and the best cutoff value of LDH is 198.9 U/L. The proportion of patients with stage T3-4 and stage III-IVB in high SII group was higher than that in low SII group ( P<0.001). Multivariate Cox regression analysis showed that N stage, SII and LDH were independent factors of OS, progression-free survival (PFS) and distant metastasis-free survival (DMFS) of NPC patients (N stage, HR=1.705, 95% CI: 1.247-2.332; HR=1.755, 95% CI: 1.342-2.295; HR=2.161, 95% CI: 1.515-3.082. SII, HR=1.525, 95% CI: 1.097-2.119; HR=1.518, 95% CI: 1.150-2.004; HR=1.837, 95% CI: 1.272-2.653. LDH, HR=2.041, 95% CI: 1.403-2.968; HR=1.725, 95% CI: 1.233-2.414; HR=2.492, 95% CI: 1.690-3.672, respectively). After PSM, SII was still an independent prognostic factor of OS, PFS and DMFS in NPC patients ( HR=1.52, 95% CI: 1.09-2.12; HR=1.52, 95% CI: 1.15-2.00; HR=1.82, 95% CI: 1.26-2.63, respectively). Combined with N 2-3 stage, SII (>447.2×10 9/L), and LDH (>198.9 U/L), patients were divided into high-(3 risk factors), intermediate- (2 risk factors) and low-risk (0-1 risk factors) groups. The 5-year OS rates of patients in low-, intermediate- and high-risk groups were 86.1%, 79.8% and 41.2% respectively, the 5-year PFS rates were 80.7%, 70.2% and 33.9% respectively, and the 5-year DMFS rates were 88.9%, 79.2% and 47.5% respectively. There were significant differences in OS, PFS and DMFS among these three groups ( P<0.001). Distant metastasis was the main failure pattern in low-, intermediate- and high-risk groups, and the highest rate of distant metastasis was 83.3% (15/31) in high-risk group. ROC curve of the risk stratification model for predicting 5-year OS of NPC patients is 0.610, which is higher than TNM stage (0.609), SII (0.574) and LDH (0.558). Conclusions:Pretreatment SII and LDH are significantly correlated with the prognosis of patients with non-metastatic NPC. The combination of SII, LDH and N stage can stratify the prognostic risk of NPC patients. The risk stratification model can enhance the accuracy of prognosis.

Objective:To evaluate the prognostic value of pretreatment systemic immune-inflammation index (SII) and lactate dehydrogenase (LDH) in non-metastatic nasopharyngeal carcinoma (NPC).Methods:We retrospectively collected the data of 839 patients with non-metastatic NPC from National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Sun Yat-sen University Cancer Center between January 2007 and October 2015. All patients received intensity modulated radiation based treatment. Optimal cutoff value of SII and LDH were determined by X-title software. The association between SII, LDH and clinical prognosis of non-metastatic NPC patients were analyzed. Kaplan-Meier method was used for survival analysis, and Log rank test was used for comparison of survival rates between groups. Propensity score matching (PSM) analysis was carried out to minimize the effects of confounding factors. The risk stratification model of prognosis by combining N stage, SII and LDH was constructed to compare the prognosis of patients in high risk group, middle risk group and low risk group, and the receiver operating characteristic (ROC) curve analysis was used to evaluate its prognostic value.Results:The optimal cutoff value of SII is 447.2×10 9/L for predicting the 5-year overall survival (OS) of NPC patients, and the best cutoff value of LDH is 198.9 U/L. The proportion of patients with stage T3-4 and stage III-IVB in high SII group was higher than that in low SII group ( P<0.001). Multivariate Cox regression analysis showed that N stage, SII and LDH were independent factors of OS, progression-free survival (PFS) and distant metastasis-free survival (DMFS) of NPC patients (N stage, HR=1.705, 95% CI: 1.247-2.332; HR=1.755, 95% CI: 1.342-2.295; HR=2.161, 95% CI: 1.515-3.082. SII, HR=1.525, 95% CI: 1.097-2.119; HR=1.518, 95% CI: 1.150-2.004; HR=1.837, 95% CI: 1.272-2.653. LDH, HR=2.041, 95% CI: 1.403-2.968; HR=1.725, 95% CI: 1.233-2.414; HR=2.492, 95% CI: 1.690-3.672, respectively). After PSM, SII was still an independent prognostic factor of OS, PFS and DMFS in NPC patients ( HR=1.52, 95% CI: 1.09-2.12; HR=1.52, 95% CI: 1.15-2.00; HR=1.82, 95% CI: 1.26-2.63, respectively). Combined with N 2-3 stage, SII (>447.2×10 9/L), and LDH (>198.9 U/L), patients were divided into high-(3 risk factors), intermediate- (2 risk factors) and low-risk (0-1 risk factors) groups. The 5-year OS rates of patients in low-, intermediate- and high-risk groups were 86.1%, 79.8% and 41.2% respectively, the 5-year PFS rates were 80.7%, 70.2% and 33.9% respectively, and the 5-year DMFS rates were 88.9%, 79.2% and 47.5% respectively. There were significant differences in OS, PFS and DMFS among these three groups ( P<0.001). Distant metastasis was the main failure pattern in low-, intermediate- and high-risk groups, and the highest rate of distant metastasis was 83.3% (15/31) in high-risk group. ROC curve of the risk stratification model for predicting 5-year OS of NPC patients is 0.610, which is higher than TNM stage (0.609), SII (0.574) and LDH (0.558). Conclusions:Pretreatment SII and LDH are significantly correlated with the prognosis of patients with non-metastatic NPC. The combination of SII, LDH and N stage can stratify the prognostic risk of NPC patients. The risk stratification model can enhance the accuracy of prognosis.

Objective:To identify the population who can obtain clinical benefit from concurrent chemoradiotherapy through the survival analysis during concurrent chemoradiotherapy in different subgroups.Methods:All data from a phase Ⅲ randomized controlled clinical trial were collected to compare the efficacy between preoperative concurrent chemoradiotherapy and preoperative radiotherapy from 2002 to 2012 in Cancer Hospital of the Chinese Academy of Medical Sciences. A total of 222 patients received radiation therapy with a median dose of 69.96 Gy (27.56-76.00 Gy). The cisplatin chemotherapy regimen was adopted and the median dose was 250 mg (100-570 mg). In total, 98 patients received intensity-modulated radiotherapy (IMRT). The survival analysis was conducted with Kaplan- Meier method and univariate analysis was performed with log-rank test. The multivariate prognostic analysis was conducted with Cox’s regression model. Results:The median follow-up time was 59 months (7-139 months). Among them, 104 patients were assigned in the chemoradiotherapy group and 118 patients in the radiotherapy alone group. The local and regional recurrence rates did not significantly differ between two groups (both P>0.05), while chemoradiotherapy tended to decrease the distant metastasis rate compared with the radiotherapy alone (14.4% vs. 24.6, P=0.058). Univariate analysis showed that concurrent chemoradiotherapy significantly increased the local recurrence-free survival in the early N stage subgroup ( P=0.009), and there was an increasing trend in patients aged≤55 years and female patients ( P=0.052, 0.066). The distant metastasis-free survival was significantly improved in T 4( P=0.048), N 3( P=0.005), non-IMRT treatment ( P=0.001) and hypopharyngeal carcinoma ( P=0.004) subgroups, there was an increasing trend in male ( P=0.064), high-and moderate-grade squamous cell carcinoma ( P=0.076) and non-surgical treatment subgroups ( P=0.063). Multivariate analyses showed that concurrent chemoradiotherapy significantly prolonged the progression-free survival and overall survival in patients aged≤55 years ( P=0.017 and 0.039), women ( P=0.041 and 0.039), high-and moderate-grade squamous cell carcinoma ( P=0.006 and 0.022), N 3 stage ( P=0.001 and 0.017), non-surgical treatment ( P=0.007 and 0.033) and non-IMRT treatment subgroups ( P=0.030 and 0.024), and it significantly increased the progression-free survival in patients with hypopharyngeal carcinoma ( P=0.022). Conclusion:Concurrent chemoradiotherapy can be actively delivered for young age, female, high-and moderate-grade squamous cell carcinoma, N 3 stage, non-surgical treatment and non-IMRT treatment patients.