Congenital heart disease (CHD) is a congenital malformation resulting from abnormal embryonic development of the heart and great vessels, accounting for approximately 25% of all congenital malformations. Children with CHD are often complicated by short stature. Although surgical treatment can improve their growth and development to a certain extent, some children still experience growth retardation after surgery. Recombinant human growth hormone (rhGH) is the main drug for treating short stature, but its efficacy and safety in the treatment of patients with concomitant CHD warrant further investigation. This article reports six cases of children with CHD and short stature who were treated with rhGH. Through a literature review, we summarize and discuss the therapeutic efficacy, follow-up experiences, and adverse reactions of rhGH treatment, aiming to provide references for clinicians in applying rhGH to treat patients with CHD and short stature.

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals ; Disease Models, Animal ; Mice ; Pneumonia/genetics* ; Medicine, Chinese Traditional ; Male ; Humans ; Cytokines/immunology* ; Female ; Lipopolysaccharides/adverse effects* ; Lung/drug effects* ; Drugs, Chinese Herbal ; Ovalbumin ; Mice, Inbred BALB C

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

ObjectiveTo investigate the mechanism of salvianolic acid F （Sal F） in repairing the high glucose-induced injury in human kidney-2 （HK-2） cells via the B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）/cysteinyl aspartate-specific proteinase 3 （Caspase-3）/gasdermin-E （GSDME） pathway. MethodThe cell counting kit-8 （CCK-8） was used to measure the relative viability of HK-2 cells exposed to high glucose and different concentrations （2.5， 5， 10， 20 μmol·L^-1） of Sal F and the relative viability of HK-2 cells treated with Sal F for different time periods. The levels of lactate dehydrogenase （LDH） and interleukin-1β （IL-1β） in the supernatant of the cell culture were measured by the LDH assay kit and enzyme-linked immunosorbent assay （ELISA） kit， respectively. Flow cytometry combined with Annexin V-FITC/propidium iodide （PI） and Hoechst 33342/PI staining was employed to reveal the proportion of PI-positive HK-2 cells exposed to high glucose. Western blotting was employed to determine the protein levels of Bax， Bcl-2， cytochrome C， cysteinyl aspartate-specific proteinase （Caspase）-9， Caspase-3， and GSDME in the HK-2 cells exposed to high glucose and treated with Sal F. The 2，7-dichlorodihydrofluorescein diacetate fluorescence probe （DCFH-DA） and mitochondrial membrane potential assay kit （JC-1） were used to determine the production of reactive oxygen species （ROS） and the mitochondrial membrane potential in the HK-2 cells exposed to high glucose and treated with Sal F. ResultCompared with the blank group， the model group showed decreased cell viability （P<0.01）， elevated levels LDH and IL-1β， increased proportion of PI-positive cells （P<0.01）， up-regulated protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME （P<0.01）， down-regulated protein level of Bcl-2 （P<0.01）， decreased mitochondrial membrane potential， and excessive ROS accumulation. Compared with the model group， Sal F repaired the high glucose-induced injury in HK-2 cells （P<0.05）， lowered the levels of LDH and IL-1β （P<0.05， P<0.01）， and decreased the proportion of PI-positive cells （P<0.01）. In addition， Sal F down-regulated the protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME and up-regulated the protein level of Bcl-2 （P<0.05， P<0.01）， increased the mitochondrial membrane potential， and decreased the accumulation of ROS in HK-2 cells. ConclusionSal F can reduce the production of ROS， restore the balance of mitochondrial membrane potential， and inhibit pyroptosis via the Bax/Caspase-3/GSDME signaling pathway to repair the high glucose-induced injury in HK-2 cells.

Objective To investigate the effects of Sinensetin on intestinal mucosal dysfunction in mice with ulcerative colitis by inhibiting iron death pathway.Methods C57BL/6 mice were randomly divided into control group,model group,positive group and low,medium,high dose experimental groups.UC model was established in all groups except control group.At the same time,control group and model group were given the same amount of 0.9％NaCl by intragastric administration;low,medium and high dose experimental groups were given intragastric administration of 10,20 and 40 mg·kg-1 sinensetin;positive group was given intragastric administration of 50 mg·kg-1mesalazine,once a day,for 14 days.The general condition,colon length,intestinal weight index,disease activity index(DAI)and mucosal damage index(CMDI)scores of mice were observed.D-lactic acid content(D-LA),diamine oxidase(DAO),interleukin-1 β(IL-1 β),interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)were detected by the kit.The expression of compact connecting closure protein(Occludin),tight junction protein-1(Claudin-1),non-glycosylated xCT(SLC7A11)and glutathione peroxidase 4(GPX4)were detected by Western blot.Results The serum DAO of control group,model group and low,medium,high dose experimental groups were(9.23±1.28),(34.61±3.95),(29.36±3.34),(23.41±2.74)and(16.75±2.57)U·mL-1,respectively;serum D-LA were(7.04±1.71),(18.25±1.05),(15.14±1.56),(11.43±1.70)and(8.93±1.56)ng·mL-1,respectively;the expression of Occludin protein were 0.89±0.08,0.25±0.05,0.37±0.03,0.48±0.05 and 0.66±0.07,respectively;the expression of Claudin-1 protein were 0.83±0.09,0.33±0.05,0.47±0.05,0.59±0.06 and 0.72±0.07,respectively;GPX4 protein expression were 0.85±0.06,0.23±0.05,0.36±0.04,0.53±0.06 and 0.72±0.08,respectively;SLC7A11 protein expressions were 0.95±0.06,0.30±0.04,0.42±0.05,0.65±0.05 and 0.84±0.05,respectively.There was statistical significance between control group and model group(all P＜0.05).There were significant differences in the above indexes between model group and low,medium,high dose experimental groups(all P＜0.05).Conclusion Sinensetin can inhibit iron death pathway and improve intestinal mucosal dysfunction in mice with ulcerative colitis.