OBJECTIVE: Therapeutic angiogenesis has become a promising approach for treating ischemic heart disease (IHD). The present study aims to investigate the effects of Qishen Granule (QSG) on angiogenesis in myocardial ischemia (MI) and the potential mechanism. METHODS: In vivo study was conducted on rat model of myocardial infarction. QSG was performed daily at a dose of 2.352 g/kg for four weeks. Cardiac function was assessed by echocardiogram and pro-angiogenic effects were evaluated by Laser Doppler and CD31 expression. Oxygen-glucose deprivation (OGD) was applied in cultured human umbilical vein endothelial cells (HUVECs). Cell viability, wound healing and tube formation assay were used to test functions of HUVECs. ELISA and Western blots were used to assess protein expressions of bone morphogenetic protein 2-delta-like 4-notch homolog 1 (BMP2-Dll4-Notch1) signaling pathway. RESULTS: The results showed that QSG improved heart function, cardiac blood flow and microvessel density in myocardial ischemic rats. In vitro, QSG protected HUVECs by promoting the cell viability and tube formation. QSG upregulated bone morphogenetic protein-2 (BMP2) and downregulated delta-like 4 (Dll4) and notch homolog 1 (Notch1) expressions both in rats and HUVECs. CONCLUSION QSG protected against MI by promoting angiogenesis through BMP2-Dll4-Notch1 pathway. BMP2 might be a promising therapeutic target for IHD.

Objective:To understand the current status of pubertal sexual characteristics development of girls aged 6-18 years in Tongzhou District of Beijing and to compare the differences in sexual characteristics development among girls characterized as thin, normal, overweight, and obese.Methods:A cross-sectional survey was conducted among 2 844 girls aged 6-18 years in Tongzhou District of Beijing from September 2022 to July 2023. The developmental stages of breast and pubic hair were assessed on site, and menarche status was inquired. Weight and height were measured. The girls were subsequently characterized into thin, normal, overweight and obese groups. Basic information (including family and personal history) was obtained through questionnaires. Probit probability unit regression was applied to calculate the age of each Tanner stage of sexual characteristics development and the age of menarche. The χ 2 test was applied to compare the counting data between two or multiple groups. Results:A total of 2 844 girls were surveyed and 2 704 girls met the inclusion criteria, resulting in a valid response rate of 95.1%. Among these girls, 1 105 (40.9%) were aged 6-9 years, 1 053 (38.9%) were aged 10-13 years, and 546 (20.2%) were aged 14-18 years. The of height-for-age Z-score (HAZ), weight-for-age Z-score (WAZ), and body mass index-for-age Z-score (BAZ) were 0.46(-0.23,1.16), 0.69(-0.16,1.67), and 0.67(-0.27,1.73) respectively. The prevalences of thin, overweight, and obesity were respectively 1.7% (45/2 704), 17.3% (467/2 704), and 19.9% (538/2 704), respectively. There were 45 girls in the thin group, 1 654 girls in the normal weight group, 1 005 girls in the overweight and obesity group. The age of Tanner stage breast 2 (B2), Tanner stage pubic hair 2 (P2), and menarche was 9.0 (95% CI 8.9-9.1), 10.5 (95% CI 10.4-10.6), and 11.4 (95% CI 11.3-1.5) years, respectively. The current status of breast and pubic hair maturity in girls with pubertal development shows that 64.6% (1 211/1 874) of these girls had breast development preceding pubic hair development, 32.4% (607/1 874) had concurrent breast and pubic hair development, and 3.0% (56/1 874) had pubic hairs development preceding breast development. The interval age between B2 and B5 was 4.7 (95% CI 4.6-4.8) years, between P2 and P5 was 4.5 (95% CI 4.4-4.6) years, and between B2 and menarche was 2.4 (95% CI 2.3-2.5) years. The ages of sexual characteristics development in overweight and obese groups were earlier than that in normal and thin groups. The ages of B2 in thin, normal, overweight, and obese groups were 10.0 (95% CI 9.5-10.6), 9.3 (95% CI 9.2-9.4), and 8.6 (95% CI 8.4-8.7) years, respectively. The age of menarche in thin, normal, overweight, and obese groups were 13.1 (95% CI 12.4-13.7), 11.6 (95% CI 11.4-11.7), and 11.1 (95% CI 11.0-11.2) years, respectively. The interval ages between B2 and B5 and between P2 and P5 was 4.5 and 4.1 years, respectively in the overweight and obese groups, and those in normal group and thin group was 4.7 and 4.5 years, 4.6 and 4.7 years, respectively. Conclusions:The ages of sexual characteristics development and menarche tend in Tongzhou District of Beijing to be earlier than that being reported of Beijing's survey 20 years ago. Girls characterized as overweight and obese not only start puberty at an earlier age than girls of normal weight, but also have a shorter developmental process.

Objective:To investigate the effects of enriched environments on behavioral development at toddler period of preterm who had experienced early repeated operative pain.Methods:A cross-sectional study was conducted. A total of 80 high-risk preterm children of 2 years of age, who had experienced repeated pain stimuli in the neonatal intensive care unit (NICU), were enrolled as preterm group from the High-risk Children Clinic of Children′s Hospital of Nanjing Medical University from October 2016 to March 2021. Furthermore, 39 full-term healthy children, aged 2 years, who were undergoing routine check-ups during the same period, were selected as the full-term group. The preterm group was further divided into preterm intervention group and preterm non-intervention group based on the implementation of enriched environment interventions. Data of neonatal characteristics from 3 groups were collected. Growth and development indicators at the age of 2 years were measured. Neuropsychological development evaluated by Gesell developmental scale. Behavioral development evaluated by child behavior check list. The salivary cortisol levels in response to novelty (baseline, task, end) were collected. The family environment, including maternal parenting pressure, were evaluated through a survey questionnaire. One-way ANOVA and least significant difference (LSD) tests were used to compare physical development, maternal parenting stress, Gesell neuropsychological development, and behavioral problems among the 3 groups. A repeated-ANOVA and LSD tests were employed to compare the patterns of salivary cortisol secretion. Pearson correlation analysis was used to explore the influencing factors related to neuropsychological and behavioral development and cortisol level.Results:There were 44 cases in the preterm intervention group (17 males, gestational age of (31.3±2.8) weeks), and 36 in the preterm non-intervention group (29 males, gestational age of (32.5±2.6) weeks). The full-term group consisted of 39 children (23 males, gestational age of (39.3±2.1) weeks). At 2 years of age, the height, weight, and head circumference of the preterm intervention group and non-intervention group were all lower than those of the full-term group (all P<0.05).The Gesell developmental schedule showed that the preterm non-intervention group scored all lower in gross motor, fine motor, adaptive, language and personal-social domains compared to the full-term group (91±7 vs. 97±6, 88±9 vs. 94±6, 89±8 vs. 99±8, 84±10 vs. 100±15, 89±7 vs. 95±6), with statistical significance (all P<0.01). The preterm intervention group scored all higher than the preterm non-intervention group in gross motor, fine motor, adaptive and language domains (all P<0.05), with no significant difference compared to the full-term group (all P>0.05). The number of needle painful procedures during hospitalization in NICU of the non-intervention group was negatively correlated to the adaptive development quotient ( r=-0.48, P<0.05). Furthermore, the preterm non-intervention group exhibited higher scores in social withdrawal, depression, somatic complaints, aggression, and destructive behaviors compare to the full-term group and preterm intervention group ( F=8.07, 5.67, 7.72, 7.90, 7.06; all P<0.05); while the preterm intervention group showed no significant difference compared to full-term group (all P>0.05). Behavioral problems (social withdrawal and depression) in the preterm non-intervention group were positively correlated with maternal parenting stress ( r=0.66, 0.50; both P<0.05). In response to novel visual stimuli and cognitive challenges, the preterm non-intervention group had significantly higher salivary cortisol levels compared to the full-term group ( P=0.006), which were negatively correlated with the frequency of early painful procedures ( r=-0.83, -0.80; both P<0.01). There was no significant difference in cortisol secretion pattern between the intervention group and the full-term group ( P=0.772). Conclusion:Enriched environmental interventions can improve neuropsychological development, decrease behavioral problems, and down-regulate consistent high cortisol response to task in preterm infants who have experienced repeated procedural pain in the NICU by the age of 2 years.

Objective:To explore the causal relationship between blood metabolites and keloids.Methods:The study was a two-sample bidirectional Mendelian randomization (MR) analysis-based study. Blood metabolites of 7 824 adult volunteers and 8 299 participants and data related to 481 912 keloid patients were obtained from the genome-wide association studies (GWAS) Catalog database. Single nucleotide polymorphisms (SNPs) significantly associated with blood metabolites and keloids were screened for inclusion as instrumental variables in the MR analysis by setting a significance threshold of P<1.0×10 -5, chain imbalance analysis [ r2 = 0.001, kilobase pairs (kb) = 10, 000)], and the F statistic ( F≥10) . Five method of MR analysis, i.e., inverse variance weighting (IVW) as the main method and MR-Egger regression, weighted median, simple modeling, and weighted modeling as auxiliary method, were used to analyze the causal relationship between blood metabolites (exposure factors) and keloids (outcome variables) . Sensitivity analyses were performed on eligible blood metabolite SNPs to assess the reliability and stability of the findings: heterogeneity was assessed by Cochran Q-test and MR-Egger regression test, MR Egger intercept test to rule out horizontal pleiotropy, leave-one-out test to determine if the presence of a single SNP significantly affected the result of the MR analyses, MR-PRESSO method was used to test for outliers of SNPs, which were corrected by false discovery rate (FDR) (FDR <0.2) to control the false positive rate. Reverse MR analysis was performed with keloid as the exposure factor, and blood metabolites screened by the aforementioned MR analysis were used as outcome variables for effect analysis and sensitivity analysis. The data were analyzed using R 4.3.2 software and the TwoSampleMR program package therein, and the causal effect values of the MR analysis were expressed as the ratio ( OR) and 95% CI, with P<0.05 being considered as a statistically significant difference, i. e., the evidence of a potential causal effect was substantial. Forest plots, funnel plots, and scatter plots were constructed to visualize the result of MR analysis and sensitivity analysis. Results:A total of 1 400 blood metabolites with 34 843 SNPs were obtained from the GWAS Catalog database, all of which were consistent with the hypothesis that genetic variants are closely associated with exposure factors; a total of 24 197 210 SNPs were obtained from the keloid dataset. IVW analysis revealed that one blood metabolite, succinyl taurine (16 ∶ 1n-7), had 28 SNPs with keloid with a causal relationship ( OR=1.13, 95% CI 1.06-1.19, P<0.001, FDR=0.070) ; MR-Egger regression method ( OR = 1.11, 95% CI 1.04-1.19, P=0.005), weighted median method ( OR = 1.11, 95% CI 1.02-1.20, P=0.014) and weighted modeling method ( OR=1.12, 95% CI 1.04 to 1.20, P=0.004) analyses also showed that succinyl taurine (16 ∶ 1n-7) was a risk factor for keloid disease; the result of the simple modeling method only showed that the causal relationship between succinyl taurine (16 ∶ 1n-7) and keloid disease was not significant ( OR=1.10, 95% CI 0.85-1.41, P=0.485) . MR overall analysis showed a significant positive causal relationship between succinyl taurine (16 ∶ 1n-7) and keloid, i.e., elevated levels of succinyl taurine (16 ∶ 1n-7) were associated with an increased risk of keloid disease. Cochran Q-test ( Q = 26.98, P=0.465), MR-Egger regression test ( Q = 26.65, P = 0.428), MR-Egger intercept test ( P = 0.574), and MR-PRESSO composite test ( P=0.569) showed that there was no heterogeneity and horizontal pleiotropy among SNPs ( P>0.05) ; the leave-one-out test confirmed that individual SNPs did not have a significant effect on the overall result, indicating that the result had reliability and stability. The inverse MR analysis suggested that there was no causal relationship between keloid on succinyl taurine (16 ∶ 1n-7) (IVW: OR=0.98, 95% CI 0.93-1.04, P=0.490) . Conclusions:There is a significant positive causal relationship between the blood metabolite succinyl taurine (16 ∶ 1n-7) and keloids, and succinyl taurine (16 ∶ 1n-7) is a risk factor for keloid disease.

Objective:To explore the causal relationship between blood metabolites and keloids.Methods:The study was a two-sample bidirectional Mendelian randomization (MR) analysis-based study. Blood metabolites of 7 824 adult volunteers and 8 299 participants and data related to 481 912 keloid patients were obtained from the genome-wide association studies (GWAS) Catalog database. Single nucleotide polymorphisms (SNPs) significantly associated with blood metabolites and keloids were screened for inclusion as instrumental variables in the MR analysis by setting a significance threshold of P<1.0×10 -5, chain imbalance analysis [ r2 = 0.001, kilobase pairs (kb) = 10, 000)], and the F statistic ( F≥10) . Five method of MR analysis, i.e., inverse variance weighting (IVW) as the main method and MR-Egger regression, weighted median, simple modeling, and weighted modeling as auxiliary method, were used to analyze the causal relationship between blood metabolites (exposure factors) and keloids (outcome variables) . Sensitivity analyses were performed on eligible blood metabolite SNPs to assess the reliability and stability of the findings: heterogeneity was assessed by Cochran Q-test and MR-Egger regression test, MR Egger intercept test to rule out horizontal pleiotropy, leave-one-out test to determine if the presence of a single SNP significantly affected the result of the MR analyses, MR-PRESSO method was used to test for outliers of SNPs, which were corrected by false discovery rate (FDR) (FDR <0.2) to control the false positive rate. Reverse MR analysis was performed with keloid as the exposure factor, and blood metabolites screened by the aforementioned MR analysis were used as outcome variables for effect analysis and sensitivity analysis. The data were analyzed using R 4.3.2 software and the TwoSampleMR program package therein, and the causal effect values of the MR analysis were expressed as the ratio ( OR) and 95% CI, with P<0.05 being considered as a statistically significant difference, i. e., the evidence of a potential causal effect was substantial. Forest plots, funnel plots, and scatter plots were constructed to visualize the result of MR analysis and sensitivity analysis. Results:A total of 1 400 blood metabolites with 34 843 SNPs were obtained from the GWAS Catalog database, all of which were consistent with the hypothesis that genetic variants are closely associated with exposure factors; a total of 24 197 210 SNPs were obtained from the keloid dataset. IVW analysis revealed that one blood metabolite, succinyl taurine (16 ∶ 1n-7), had 28 SNPs with keloid with a causal relationship ( OR=1.13, 95% CI 1.06-1.19, P<0.001, FDR=0.070) ; MR-Egger regression method ( OR = 1.11, 95% CI 1.04-1.19, P=0.005), weighted median method ( OR = 1.11, 95% CI 1.02-1.20, P=0.014) and weighted modeling method ( OR=1.12, 95% CI 1.04 to 1.20, P=0.004) analyses also showed that succinyl taurine (16 ∶ 1n-7) was a risk factor for keloid disease; the result of the simple modeling method only showed that the causal relationship between succinyl taurine (16 ∶ 1n-7) and keloid disease was not significant ( OR=1.10, 95% CI 0.85-1.41, P=0.485) . MR overall analysis showed a significant positive causal relationship between succinyl taurine (16 ∶ 1n-7) and keloid, i.e., elevated levels of succinyl taurine (16 ∶ 1n-7) were associated with an increased risk of keloid disease. Cochran Q-test ( Q = 26.98, P=0.465), MR-Egger regression test ( Q = 26.65, P = 0.428), MR-Egger intercept test ( P = 0.574), and MR-PRESSO composite test ( P=0.569) showed that there was no heterogeneity and horizontal pleiotropy among SNPs ( P>0.05) ; the leave-one-out test confirmed that individual SNPs did not have a significant effect on the overall result, indicating that the result had reliability and stability. The inverse MR analysis suggested that there was no causal relationship between keloid on succinyl taurine (16 ∶ 1n-7) (IVW: OR=0.98, 95% CI 0.93-1.04, P=0.490) . Conclusions:There is a significant positive causal relationship between the blood metabolite succinyl taurine (16 ∶ 1n-7) and keloids, and succinyl taurine (16 ∶ 1n-7) is a risk factor for keloid disease.

The increasing operating pressure of large public hospitals has forced hospitals to focus on opening up income sources and reducing expenditure.The purchase and maintenance of medical equipment is one of the important economic activities of hospi-tals.However,there are problems in large public hospitals,such as the argumentation for equipment acquisition ignoring evaluation of operational efficiency,the costing model that leads to a lack of willingness of departments to purchase equipment,and the lack of standard processes and systems for renting medical equipment among departments.Based on this,it explores the establishment of a medical equipment sharing operation mechanism in large public hospitals,promotes the improvement of the efficiency of medical equipment use in large public hospitals by establishing a medical equipment sharing center,standardizing the purchase of shared equipment,entering shared equipment information,setting up shared equipment leasing specifications,and clarifying the equipment return process and maintenance,so as to effectively control hospital operating costs,and help the high-quality development of public hospitals.

The increasing operating pressure of large public hospitals has forced hospitals to focus on opening up income sources and reducing expenditure.The purchase and maintenance of medical equipment is one of the important economic activities of hospi-tals.However,there are problems in large public hospitals,such as the argumentation for equipment acquisition ignoring evaluation of operational efficiency,the costing model that leads to a lack of willingness of departments to purchase equipment,and the lack of standard processes and systems for renting medical equipment among departments.Based on this,it explores the establishment of a medical equipment sharing operation mechanism in large public hospitals,promotes the improvement of the efficiency of medical equipment use in large public hospitals by establishing a medical equipment sharing center,standardizing the purchase of shared equipment,entering shared equipment information,setting up shared equipment leasing specifications,and clarifying the equipment return process and maintenance,so as to effectively control hospital operating costs,and help the high-quality development of public hospitals.

The increasing operating pressure of large public hospitals has forced hospitals to focus on opening up income sources and reducing expenditure.The purchase and maintenance of medical equipment is one of the important economic activities of hospi-tals.However,there are problems in large public hospitals,such as the argumentation for equipment acquisition ignoring evaluation of operational efficiency,the costing model that leads to a lack of willingness of departments to purchase equipment,and the lack of standard processes and systems for renting medical equipment among departments.Based on this,it explores the establishment of a medical equipment sharing operation mechanism in large public hospitals,promotes the improvement of the efficiency of medical equipment use in large public hospitals by establishing a medical equipment sharing center,standardizing the purchase of shared equipment,entering shared equipment information,setting up shared equipment leasing specifications,and clarifying the equipment return process and maintenance,so as to effectively control hospital operating costs,and help the high-quality development of public hospitals.

The increasing operating pressure of large public hospitals has forced hospitals to focus on opening up income sources and reducing expenditure.The purchase and maintenance of medical equipment is one of the important economic activities of hospi-tals.However,there are problems in large public hospitals,such as the argumentation for equipment acquisition ignoring evaluation of operational efficiency,the costing model that leads to a lack of willingness of departments to purchase equipment,and the lack of standard processes and systems for renting medical equipment among departments.Based on this,it explores the establishment of a medical equipment sharing operation mechanism in large public hospitals,promotes the improvement of the efficiency of medical equipment use in large public hospitals by establishing a medical equipment sharing center,standardizing the purchase of shared equipment,entering shared equipment information,setting up shared equipment leasing specifications,and clarifying the equipment return process and maintenance,so as to effectively control hospital operating costs,and help the high-quality development of public hospitals.

The increasing operating pressure of large public hospitals has forced hospitals to focus on opening up income sources and reducing expenditure.The purchase and maintenance of medical equipment is one of the important economic activities of hospi-tals.However,there are problems in large public hospitals,such as the argumentation for equipment acquisition ignoring evaluation of operational efficiency,the costing model that leads to a lack of willingness of departments to purchase equipment,and the lack of standard processes and systems for renting medical equipment among departments.Based on this,it explores the establishment of a medical equipment sharing operation mechanism in large public hospitals,promotes the improvement of the efficiency of medical equipment use in large public hospitals by establishing a medical equipment sharing center,standardizing the purchase of shared equipment,entering shared equipment information,setting up shared equipment leasing specifications,and clarifying the equipment return process and maintenance,so as to effectively control hospital operating costs,and help the high-quality development of public hospitals.