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1.
ACS Biomater Sci Eng ; 10(6): 3994-4008, 2024 06 10.
Article in English | MEDLINE | ID: mdl-38736179

ABSTRACT

Disruption of the symbiosis of extra/intratumoral metabolism is a good strategy for treating tumors that shuttle resources from the tumor microenvironment. Here, we report a precision treatment strategy for enhancing pyruvic acid and intratumoral acidosis to destroy tumoral metabolic symbiosis to eliminate tumors; this approach is based on PEGylated gold and lactate oxidase-modified aminated dendritic mesoporous silica with lonidamine and ferrous sulfide loading (PEG-Au@DMSNs/FeS/LND@LOX). In the tumor microenvironment, LOX oxidizes lactic acid to produce pyruvate, which represses tumor cell proliferation by inhibiting histone gene expression and induces ferroptosis by partial histone monoubiquitination. In acidic tumor conditions, the nanoparticles release H2S gas and Fe2+ ions, which can inhibit catalase activity to promote the Fenton reaction of Fe2+, resulting in massive ·OH production and ferroptosis via Fe3+. More interestingly, the combination of H2S and LND (a monocarboxylic acid transporter inhibitor) can cause intracellular acidosis by lactate, and protons overaccumulate in cells. Multiple intracellular acidosis is caused by lactate-pyruvate axis disorders. Moreover, H2S provides motive power to intensify the shuttling of nanoparticles in the tumor region. The findings confirm that this nanomedicine system can enable precise antitumor effects by disrupting extra/intratumoral metabolic symbiosis and inducing ferroptosis and represents a promising active drug delivery system candidate for tumor treatment.


Subject(s)
Ferroptosis , Lactic Acid , Pyruvic Acid , Tumor Microenvironment , Ferroptosis/drug effects , Humans , Lactic Acid/metabolism , Animals , Pyruvic Acid/metabolism , Tumor Microenvironment/drug effects , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/therapy , Cell Line, Tumor , Mice , Gold/chemistry , Silicon Dioxide/chemistry , Female , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Mice, Inbred BALB C , Cell Proliferation/drug effects , Mixed Function Oxygenases , Indazoles
2.
Nanoscale ; 16(3): 1282-1290, 2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38126775

ABSTRACT

As emerging nanosystems, nanomotors have been applied in the active treatment of many diseases. In this paper, Pt@chitosan-loaded melatonin asymmetrical nanomaterials embedded with L-serine (S, kidney injury molecule 1-targeting agent) were constructed to alleviate acute kidney injury (AKI). The Janus nanocarriers arrived at the renal injury site via the bloodstream and exhibited high permeability. Because of melatonin distribution in the kidneys combined with H2O2-stimulated O2 release, the administration of the Janus nanosystem resulted in active treatment through the motion of nanomotors by asymmetrical O2 release.


Subject(s)
Acute Kidney Injury , Melatonin , Nanostructures , Humans , Hydrogen Peroxide , Permeability , Acute Kidney Injury/drug therapy
3.
Nanoscale ; 15(14): 6745-6758, 2023 Apr 06.
Article in English | MEDLINE | ID: mdl-36942933

ABSTRACT

Effective drugs that can be quickly delivered to and retained for a long time in the renal tubule are necessary for acute kidney injury (AKI) treatment. In this study, a gold nanoparticle-modified mesoporous silica (Au@MSN-NH2)-camouflaged (methoxyphenyl)(morpholino)phosphinodithioic acid (GYY4137) asymmetrical nanosystem decorated with L-serine (S; an AKI-targeting agent) and D-Arg-dimethylTyr-Lys-Phe-NH2 (TK-SS31; a reactive oxygen species (ROS)-sensitive thioketal linker/mitochondria-targeted antioxidant) was constructed for the treatment of renal tubule and mitochondrial injury as well as the synergistic and active treatment of AKI. Due to the enhanced permeability and retention (EPR) of nanomotors, they could progressively accumulate in renal sites. The asymmetrical nanosystem achieved effective drug distribution in the kidney as well as pH-responsive hydrogen sulfide (H2S) release and ROS-responsive SS31 release, resulting in an active therapeutic effect mediated by nanomotor motion resulting from asymmetrical H2S release.


Subject(s)
Acute Kidney Injury , Metal Nanoparticles , Nanoparticles , Humans , Reactive Oxygen Species , Gold , Kidney , Hydrogen-Ion Concentration
4.
Transl Androl Urol ; 11(8): 1177-1188, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36092836

ABSTRACT

Background: This study sought to investigate the protective effects of Astragaloside IV (AS-IV) on ischemia-reperfusion (I/R) renal injury based on the keap1-Nrf2/ARE signaling pathway. Methods: A total of 36 male Sprague-Dawley rats (aged: 8 weeks; weighing: 200-220 g) were randomly divided into the following 6 groups (n=6 per group): (I) the control group; (II) the sham operation group; (III) the kidney I/R injury group (the I/R group); (IV) the kidney I/R injury group treated with 2 mg/kg of AS-IV (the low-dose group); (V) the kidney I/R injury group treated with 5 mg/kg of AS-IV (the mid-dose group); and (VI) the kidney I/R injury group treated with 10 mg/kg of AS-IV (the high-dose group). Serum creatinine (CRE), serum urea, malondialdehyde (MDA), and superoxide dismutase (SOD) were examined using enzyme-linked immunoassay kits. Cell apoptosis and the pathological damage to the renal tissue were determined by terminal deoxynucleotidyl transferase dUTP nick end labeling, hematoxylin and eosin, and periodic acid-Schiff (PAS) staining. The immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and western blot methods were used to determine the expression of Nrf2, HO-1, Bcl-2 and Bax in the kidney tissue. Results: In the I/R rat model, the serum CRE level was increased. In the acute kidney injury (AKI) and chronic kidney disease (CKD) models, AS-IV treatment significantly decreased serum CRE levels in a dose-dependent manner. AS-IV treatment also reduced the injury of renal tubular epithelial cells, increased the expression levels of Nrf2 and HO-1, decreased the rate of apoptosis, downregulated the level of MDA, and elevated the activity of SOD. In the CKD rat model, the AS-IV treatment groups had reduced renal tubular epithelial cell injury, increased expression levels of Nrf2 and HO-1, decreased MDA levels, and increased SOD activity compared to the I/R group. Conclusions: AS-IV induced the expression of Nrf2, enhanced the activity of antioxidant enzymes, reduced apoptosis, protected against renal I/R injury, and prevented AKI from transforming into CKD. These findings suggest that AS-IV is a promising drug for treating kidney injury.

5.
BMC Pediatr ; 22(1): 9, 2022 01 03.
Article in English | MEDLINE | ID: mdl-34980023

ABSTRACT

BACKGROUND: Necrotizing enterocolitis (NEC) is a gastrointestinal disease that tends to occur in premature infants. Some features may be associated with an increased probability that preterm infants with NEC will require surgical treatment. This study aimed to identify the factors that increased the probability of surgical treatment in infants with NEC. METHODS: We retrospectively analyzed the data of premature infants with NEC who were hospitalized at The Affiliated Hospital of Qingdao University from April 2011 to April 2021. According to the treatments received, these patients were divided into medical NEC group and surgical NEC group. The perinatal characteristics, clinical manifestations, and laboratory values before the onset of NEC were subjected to univariate and multivariate analyses. RESULTS: A total of 623 preterm infants with NEC (> Bell's stage I) were included in this study, including 350 (56%) who received surgical treatment and 273 (44%) who received conservative medical treatment. Multivariate analysis showed that lower gestational age (P = 0.001, odds ratio (OR) (95% CI) = 0.91[0.86-0.96]), early occurrence of NEC (P = 0.003, OR (95% CI) = 0.86 [0.77-0.95]), hemodynamically significant patent ductus arteriosus (P = 0.003, OR (95% CI) = 7.50 [2.03-28.47]), and low serum bicarbonate (P = 0.043, OR (95% CI) = 0.863 [0.749-0.995]) were associated with an increased probability of surgical treatment in preterm infants with NEC. CONCLUSIONS: Our findings were applied to identify potential predictors for surgical treatment in preterm infants with NEC, which may facilitate early decisive management.


Subject(s)
Ductus Arteriosus, Patent , Enterocolitis, Necrotizing , Infant, Premature, Diseases , Ductus Arteriosus, Patent/drug therapy , Enterocolitis, Necrotizing/epidemiology , Enterocolitis, Necrotizing/surgery , Female , Humans , Infant , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/surgery , Pregnancy , Retrospective Studies
6.
Mol Genet Genomic Med ; 9(8): e1741, 2021 08.
Article in English | MEDLINE | ID: mdl-34240825

ABSTRACT

BACKGROUND: Despite the increasing number of reports on the analysis of ATP7B variants, reports on carrier screening for Wilson's disease (WD, OMIM:277900) are rare. METHODS: Peripheral blood samples were collected from 42 patients from Qingdao Women and Children's Hospital diagnosed with WD for direct sequencing of ATP7B gene. Twelve hotspot variants of ATP7B were selected for carrier screening in Qingdao area based on an analysis of information related to ATP7B variants and literature reports in China. We screened 5012 dried blood spots (DBSs) from asymptomatic newborns in Qingdao area to estimate carrier frequency. DNA was extracted from dried blood spots. Gene sequencing was performed using multiplex polymerase chain reaction (PCR) combined with second-generation sequencing. The carrier frequency of each hotspot variant was calculated using the count data (expressed as number of carriers (%) obtained by direct counting. RESULTS: The carrier frequency of 12 hotspot variants was 1.46% (95% CI: 1.16-1.83%). The ATP7B variant with the highest carrier frequency was c.2333G>T, accounting for 54.79% of all variants screened, followed by c.2975C>T and c.2621C>T, accounting for 17.81% and 15.07% of all variants screened, respectively. CONCLUSION: Carrier frequency of ATP7B gene pathogenic variants is high in the population in Qingdao area.


Subject(s)
Copper-Transporting ATPases/genetics , Gene Frequency , Hepatolenticular Degeneration/genetics , Polymorphism, Single Nucleotide , China , Genetic Carrier Screening/statistics & numerical data , Humans , Mutation
7.
Front Endocrinol (Lausanne) ; 12: 604028, 2021.
Article in English | MEDLINE | ID: mdl-33859614

ABSTRACT

Objectives: To evaluate the clinical and economic consequences of continuous subcutaneous insulin infusion (CSII) vs. multiple daily injections (MDI) in children and adolescents with type 1 diabetes mellitus (T1DM) from a public health care system in developed areas of developing country, considering changes in glycemic Control, daily insulin requirements, lipid profile, body mass index (BMI), frequency of severe hypoglycemia and Diabetic Ketoacidosis (DKA) and diabetic complications. Methods: This was a retrospective cohort study of children and adolescents with T1DM. Data were collected at baseline and the end of every year including glycated hemoglobin (HbA1c), insulin dose, lipid profile, blood pressure, and adverse events (severe hypoglycemia and DKA). The Cost-effectiveness analysis was performed using the IQVIA CORE Diabetes Model (CDM) to simulate diabetes progression by utilizing the clinical data obtained from the two groups. The main outcome measures were Life Expectancy, Quality adjusted life years (QALYs), Total Costs and Incremental Costs and Effectiveness Ratio (ICER) of CSII compared with MDI in Chinese pediatric patients with T1DM in Qingdao City (60 years). Results: Mean HbA1c values and daily insulin doses were significantly lower in those receiving CSII therapy throughout follow-up. Mean direct lifetime costs were ¥ 67,137 higher with CSII treatment than with MDI for pediatric patients. Treatment with CSII was associated with an improvement in life expectancy of 0.41 years for pediatric patients compared with MDI based on CORE diabetes model simulation. The corresponding gains in QALYs were 0.42. These data produced corresponding ICER is ¥ 161,815 per QALY for pediatric T1DM patients in Qingdao. Sensitivity analyses suggested that our base-case assumptions were mostly robust. Conclusions: CSII is associated with improved long-term clinical outcomes compared with MDI. Based on this model analysis, CSII appears to be more cost-effective for the Qingdao TIDM pediatric population and health care system.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Insulin Infusion Systems , Insulin/administration & dosage , Adolescent , Child , Child, Preschool , China/epidemiology , Cohort Studies , Cost-Benefit Analysis , Delivery of Health Care/economics , Delivery of Health Care/organization & administration , Diabetes Mellitus, Type 1/economics , Diabetes Mellitus, Type 1/epidemiology , Drug Administration Schedule , Female , Humans , Injections, Subcutaneous , Insulin/economics , Insulin Infusion Systems/economics , Male , Public Health/economics , Retrospective Studies , Treatment Outcome
8.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(2): 116-120, 2021 Feb.
Article in Chinese | MEDLINE | ID: mdl-33627203

ABSTRACT

OBJECTIVE: To study the clinical effect of continuous subcutaneous insulin infusion (CSⅡ) versus multiple daily injection (MDI) on blood glucose control in children with type 1 diabetes mellitus (T1DM). METHODS: A retrospective analysis was performed on the medical data of 91 children with T1DM who were treated with CSⅡ for more than 1 year and 75 children with T1DM who were treated with MDI. The two groups were compared in terms of glycosylated hemoglobin (HbA1C) and the recurrence of diabetic ketoacidosis (DKA) to evaluate the difference in the efficacy during the 3-year follow-up. A survey was conducted for the children in the CSⅡ group and their family members to investigate the degree of satisfaction with insulin pump. RESULTS: There was no significant difference in age, sex, and course of diabetes between the CSⅡ and MDI groups at disease onset and in the first year, the second year, and the third year of follow-up (P > 0.05). There was no significant difference in the HbA1C level between the two groups at disease onset (P > 0.05), but in the first year of follow-up, the CSⅡ group had a significantly lower HbA1C level than the MDI group (P=0.04). There was no significant difference in the HbA1C level between the two groups in the second year and the third year of follow-up (P > 0.05). The CSⅡ group had a higher proportion of children with HbA1C < 7.5% than the MDI group in the first year, the second year, and the third year of follow-up (P > 0.05). Within the 3 years of follow-up, 2 children in the CSⅡ group and 8 in the MDI group experienced the recurrence of DKA. In the third year of follow-up, there was no significant difference in blood pressure and blood lipids between the CSⅡ and MDI groups (P > 0.05). Most children and their family members (87%) were satisfied with CSⅡ treatment. CONCLUSIONS: Children with T1DM treated with CSⅡ have a better control of blood glucose than those treated with MDI, and children and their family members are satisfied with CSⅡ treatment. Therefore, it holds promise for clinical application.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetic Ketoacidosis , Insulins , Child , Diabetes Mellitus, Type 1/drug therapy , Follow-Up Studies , Humans , Retrospective Studies
9.
J Surg Res ; 259: 458-464, 2021 03.
Article in English | MEDLINE | ID: mdl-33059908

ABSTRACT

BACKGROUND: Perioperative complications are common during the surgical treatment of pediatric retroperitoneal teratoma (RPT). Some clinical and radiographic features could be associated with perioperative complications. This study was designed to identify the factors associated with such complications. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of RPT patients who underwent surgical treatment at the Department of Pediatric Surgery of The Affiliated Hospital of Qingdao University between January 2008 and January 2020, including demographics, imaging data, intraoperative findings, perioperative complications, pathological data, and outcomes. RESULTS: A total of 91 patients were included in this study, including 30 boys and 61 girls. Of these, 71 patients (78%) were 1 y old or younger. Thirty-eight patients (41%) had perioperative complications (44 intraoperative and 7 postoperative). Preoperative imaging studies showed that the tumor distorted adjacent arteries, veins, and organs in all patients. More veins and organs were displaced and distorted by the tumor in patients who had perioperative complications. Multivariate analysis showed that the number of organs compressed and distorted by the tumor was significantly related to perioperative complications (odds ratio 1.69, 95% confidence interval 1.19-2.41). CONCLUSIONS: Surgical treatment of RPT is complex and challenging. As majority are benign, a complete excision is usually curative. The number of organs compressed and distorted by the tumor is positively related to perioperative complications.


Subject(s)
Intraoperative Complications/epidemiology , Postoperative Complications/epidemiology , Retroperitoneal Neoplasms/surgery , Teratoma/surgery , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Intraoperative Complications/etiology , Intraoperative Complications/prevention & control , Male , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Retroperitoneal Neoplasms/blood supply , Retroperitoneal Neoplasms/diagnosis , Retroperitoneal Neoplasms/pathology , Retroperitoneal Space/diagnostic imaging , Retroperitoneal Space/surgery , Retrospective Studies , Risk Factors , Teratoma/blood supply , Teratoma/diagnosis , Teratoma/pathology , Treatment Outcome
10.
Medicine (Baltimore) ; 99(34): e21635, 2020 Aug 21.
Article in English | MEDLINE | ID: mdl-32846772

ABSTRACT

INTRODUCTION: The present study is carried out to review the clinical data and gene detection results of a pediatric patient with short stature, and to summarize the relationship between clinical phenotype and genotype of the child with Aggrecan (ACAN) gene mutation. PATIENT CONCERNS: Our study was started with the observation and follow-up of a 5-year-4-month-old full-term child with short stature accompanied by central precocious puberty (CPP). DIAGNOSIS: Gene sequencing showed that there was a new heterozygous mutation C.2164C >G(p.P722A) in exon 11 of ACAN gene, which was inherited from her father. INTERVENTIONS: The child was treated by growth hormone for 6 months with mild growth, and accelerated bone age (BA) after the presence of precocious puberty. The child was diagnosed with CPP, and was provided with combined gonadotropinreleasing hormone (GnRH) therapy. OUTCOMES: The height of the pediatric patient was 99.4 cm (-3.13SDS) on admission, which was 111.9 cm (-2.08SDS) at the age of 6 years and 10 months, with a growth rate of 8.1 cm/year. There was no significant increase in BA of the pediatric patient after 1 year of follow-up. CONCLUSION: Literature review indicated that the clinical manifestations of ACAN gene mutation are the most common in idiopathic short stature, most of which are familial inheritance and can also be sporadic. Some children may also have osteoarthritis, disc herniation or degeneration. In most cases, children may have advanced BA, and retardation of BA is also found in some cases. To sum up, growth hormone combined with GnRH analogue treatment can effectively improve body height of children by postponing their adolescence. Meanwhile, ACAN gene mutation shall be considered for small-for-gestational-age children without significant growth catch-up and with family history.


Subject(s)
Aggrecans/genetics , Dwarfism/genetics , Puberty, Precocious/genetics , Child, Preschool , Dwarfism/complications , Female , Follow-Up Studies , Genotype , Humans , Phenotype , Puberty, Precocious/complications
11.
AMB Express ; 10(1): 104, 2020 Jun 01.
Article in English | MEDLINE | ID: mdl-32488691

ABSTRACT

Maslinic acid is an active member of pentacyclic triterpenes predominantly found in dietary plants including hawthorn berries and olive fruit skins. It has been reported to show immense pharmacological and biological importance including anticancer property. This research was initiated to explore the anticancer potential of maslinic acid against human neuroblastoma. The effects of maslinic acid on cellular apoptosis, ROS generation, cell migration and invasion, caspase activation and targeting MAPK/ERK signaling pathway were investigated. The proliferation percentage was calculated by performing of MTT assay. AO/EB and annexin V/PI staining assays along with western blotting were used to monitor the apoptosis and expressions of apoptosis connected proteins. Spectrofluorometry was used for ROS monitoring. To assess the anti-metastatic effects of maslinic acid on neuroblastoma cells, transwell chambers assays for migration as well as invasion were executed. Western blotting was implemented to establish the expressions of MAPK/ERK signaling pathway connected proteins. Results evidenced remarkable anticancer potential of maslinic acid against human neuroblastoma. It induced dose as well as time reliant anti-proliferative effects against SHSY-5Y cells selectively. The underlying mechanism of cancer suppressive effects of maslinic acid was found to mediate via caspase-dependent apoptosis. Further, ROS production amplified terrifically with exposure of SHSY-5Y to higher maslinic acid doses. Cell migration and invasion in SHSY-5Y cells were both reduced remarkably by maslinic acid. Finally, the activity of proteins associated with MAPK/ERK signaling pathway was found to be significantly reduced with increasing maslinic acid doses. In conclusion, it was observed that maslinic acid possesses a great anti-neuroblastoma potential and could be considered for its chemotherapy provided further investigations are recommended.

12.
Life Sci ; 256: 117985, 2020 Sep 01.
Article in English | MEDLINE | ID: mdl-32562692

ABSTRACT

AIMS: To assess the combination therapy of anti-CD20 mabs and adenovirus-mediated interleukin-10 (IL-10) gene delivery on the prevention of type 1 diabetes (T1D) in non-obese diabetes (NOD) mice. MAIN METHODS: In present study, we simultaneously blocked the B cell interactions and recovered the Th cell subset proportion by using through anti-CD20 Mab and adenovirus-mediated gene delivery of IL-10, respectively. After 9 consecutive days of combination therapy, various measurements, including hematoxylin-eosin staining (HE), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling assay (TUNEL), immunohistochemistry, ELISA, PCR and western blot were applied to further assess the efficacy. KEY FINDINGS: The results suggested that the combination intervention reduced the T1D-associated morbidity of NOD mice, promote insulin secretion, control blood glucose and ease pancreatitis. Moreover, the combination therapy might play a protective role in pancreatic ß cells by suppressing the expression of TNF-α and Fas, blocking the Caspase-8 and Caspase-3 apoptotic pathways and activating the Bcl-2 anti-apoptotic pathway. Finally, the combination intervention may up-regulate the gene expression of CK-19 and PDX-1 and further accelerate the differentiation and proliferation of pancreatic ß cells. SIGNIFICANCE: Therefore, the combination intervention with anti-CD20 mabs and the IL-10 gene plays a role in the prevention of T1D to some extent in NOD mice.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antigens, CD20/administration & dosage , Apoptosis/drug effects , Diabetes Mellitus, Type 1/drug therapy , Interleukin-10/administration & dosage , Pancreatitis/drug therapy , Adenoviridae/genetics , Animals , Antibodies, Monoclonal/genetics , Antigens, CD20/genetics , Apoptosis/genetics , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/pathology , Drug Therapy, Combination , Female , Interleukin-10/genetics , Male , Mice , Mice, Inbred NOD , Pancreatitis/genetics , Pancreatitis/pathology
13.
Surg Radiol Anat ; 42(12): 1467-1473, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32424682

ABSTRACT

PURPOSE: To study the variations of the right branch of the hepatic portal vein in children. METHODS: A total of 810 children's abdominal CT images were reconstructed with three-dimensional (3D) simulation software, Variations of the right branch of the hepatic portal vein were analyzed and classified. RESULTS: The most common anatomy (type A) was seen in 355 patients (43.83%). Trifurcation in the right anterior portal vein (type B) variation was seen in 250 cases (30.86%). The right posterior portal vein arched without obvious branching (type C) was seen in 71 cases (8.77%). There were 134 special variants (16.54%) named type D, including 14 cases (1.73%) with the right anterior branch in four sub-branches, 13 cases (1.60%) in one trunk and multiple sub-branches, 92 cases (11.36%) originating from the left trunk of the portal vein, and 15 cases (1.85%) with the VI segment of the portal vein originating from the right anterior branch of the portal vein. CONCLUSION: Variations in the right branch of the hepatic portal vein seems to be very frequent. Recognition of such variations is important in the preoperative evaluation of children with surgery planned, because these variations may have implications for anatomy-guided liver resection and for planning the operative approach.


Subject(s)
Anatomic Variation , Portal Vein/anatomy & histology , Adolescent , Child , Child, Preschool , Female , Humans , Imaging, Three-Dimensional , Infant , Male , Portal Vein/diagnostic imaging , Retrospective Studies , Tomography, Spiral Computed
14.
Indian Pediatr ; 56(9): 792-794, 2019 09 15.
Article in English | MEDLINE | ID: mdl-31638014

ABSTRACT

BACKGROUND: Bainbridge-Ropers syndrome is a rare autosomal dominant genetic disorder. CASE CHARACTERISTICS: A 26-day-old neonate presented with feeding difficulties, excessive sleeping, and hirsutism over forehead and lumbosacral skin. OUTCOME: Whole-exome sequencing identified a novel nonsense mutation. MESSAGE: We report a novel mutation in a Chinese neonate with Bainbridge-Ropers syndrome.


Subject(s)
Codon, Nonsense , Craniofacial Abnormalities/diagnosis , Disorders of Excessive Somnolence/diagnosis , Muscle Hypotonia/diagnosis , Psychomotor Disorders/diagnosis , Transcription Factors/genetics , Craniofacial Abnormalities/genetics , Disorders of Excessive Somnolence/genetics , Failure to Thrive/diagnosis , Failure to Thrive/genetics , Female , Genetic Markers , Hirsutism/diagnosis , Hirsutism/genetics , Humans , Infant, Newborn , Muscle Hypotonia/genetics , Psychomotor Disorders/genetics , Syndrome
15.
Pharmacology ; 104(5-6): 258-266, 2019.
Article in English | MEDLINE | ID: mdl-31344701

ABSTRACT

Diabetic nephropathy (DN) is a chronic complication of diabetes, and thus the present investigation evaluates the nephroprotective effect of anemonin against streptozotocin (STZ)-induced DN rats. Diabetes was induced by intraperitoneal administration of STZ (50 mg/kg) on day 2 and 3 postnatal, and rats were kept as such for the duration of 12 weeks. Thereafter, rats were treated with anemonin 75 and 150 mg/kg per oral for the period 4 week which means between the period of 12-16 weeks. Effect of anemonin was estimated by determining the blood glucose, markers of nephropathy, and mediators of inflammation in the serum and activity of tumor necrosis factor-α (TNF-α)converting enzyme (TACE) in the kidney tissue of DN rats. Moreover, reverse transcriptase polymerase chain reaction and western blot assay were determined in the kidney tissue homogenate of DN rats. Histopathology study was done by Periodic acid-Schiff's and masson staining for the pathological changes and apoptosis of podocytes in the kidney tissue of DN rats. Moreover, production of reactive oxygen species (ROS) was estimated in the kidney tissue by 2',7'-dichlorofluorescein staining. Data of study reveal that anemonin significantly reduces (p < 0.01) the blood glucose and markers of renal injury in the serum and urine of DN rats. There was a reduction in the level of cytokines in the serum, and production of ROS and activity of TACE were reduced in the kidney tissue of the anemonin-treated group than in the DN group. Expression of iRhom-2, TACE, TNF-α, and inducible nitric oxide synthase protein and histopathology of kidney tissue were attenuated in the anemonin-treated group in DN rats. In conclusion, data of study reveal that treatment with anemonin ameliorates progression of renal injury by regulating TACE/iRhom-2 signaling pathway.


Subject(s)
ADAM17 Protein/metabolism , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/drug therapy , Furans/therapeutic use , Intracellular Signaling Peptides and Proteins/metabolism , Protective Agents/therapeutic use , ADAM17 Protein/genetics , Animals , Animals, Newborn , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetic Nephropathies/genetics , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Furans/pharmacology , Intracellular Signaling Peptides and Proteins/genetics , Kidney/drug effects , Kidney/metabolism , Oxidative Stress/drug effects , Protective Agents/pharmacology , Rats, Sprague-Dawley , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
16.
Sci Rep ; 5: 11394, 2015 Jun 22.
Article in English | MEDLINE | ID: mdl-26096712

ABSTRACT

Interleukin-6 (IL-6) plays a contributory role in the progression and severity of many forms of cancer; it however remains unclear whether the relevance between circulating IL-6 and cancer is causal. We therefore meta-analyzed published articles in this regard using IL-6 gene -174G/C variant as an instrument. Seventy-eight and six articles were eligible for the association of -174G/C variant with cancer and circulating IL-6, respectively. Overall analyses failed to identify any significance between -174G/C and cancer risk. In Asians, carriers of the -174CC genotype had an 1.95-fold increased cancer risk compared with the -174GG genotype carriers (P = 0.009). By cancer type, significance was only attained for liver cancer with the -174C allele conferring a reduced risk under allelic (odds ratio or OR = 0.74; P = 0.001), homozygous genotypic (OR = 0.59; P = 0.029) and dominant (OR = 0.67; P = 0.004) models. Carriers of the -174CC genotype (weighted mean difference or WMD = -4.23 pg/mL; P < 0.001) and -174C allele (WMD = -3.43 pg/mL; P < 0.001) had circulating IL-6 reduced significantly compared with the non-carriers. In further Mendelian randomization analysis, a reduction of 1 pg/mL in circulating IL-6 was significantly associated with an 12% reduced risk of liver cancer. Long-term genetically-reduced circulating IL-6 might be causally associated with a lower risk of liver cancer.


Subject(s)
Interleukin-6/blood , Interleukin-6/genetics , Liver Neoplasms/blood , Liver Neoplasms/genetics , Asian People , Genetic Predisposition to Disease , Genotype , Humans , Liver Neoplasms/epidemiology , Polymorphism, Single Nucleotide , Random Allocation
17.
J Cardiovasc Pharmacol ; 65(5): 480-4, 2015 May.
Article in English | MEDLINE | ID: mdl-25945865

ABSTRACT

OBJECTIVE: To observe the changes of serum heart-type fatty acid-binding protein (h-FABP) and brain natriuretic peptide (BNP) in children with chronic heart failure (CHF) and evaluate the effects of carvedilol. METHODS: A total of 36 patients with CHF, including 17 of endocardial fibroelastosis and 19 of dilated cardiomyopathy, were enrolled and were randomly divided into a carvedilol treatment group (group A) and a conventional treatment group (group B). Group A (n = 16) was treated with carvedilol and conventional treatment and group B (n = 20) was managed with conventional treatment only. Thirty healthy children were enrolled as controls. The concentrations of serum h-FABP and BNP were measured by enzyme-linked immunosorbent assay, and the left ventricular end-systolic diameter, left ventricular end-diastolic diameter, left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and cardiac index (CI) were measured by echocardiography. RESULTS: The concentrations of serum h-FABP and BNP in patients with CHF were significantly higher than in the control group (21.7 ± 4.3 ng/mL vs. 6.3 ± 1.7 ng/mL, 582.4 ± 180.6 pg/mL vs.31.2 ± 9.8 pg/mL, all P < 0.01), positively correlated with the degree of heart failure (all P < 0.01), and were both higher in groups endocardial fibroelastosis and dilated cardiomyopathy than in the control group (all P < 0.01), but there was no statistically significant difference between the 2 groups (P > 0.05). h-FABP concentration in patients with CHF was positively correlated with BNP (r = 0.78, P < 0.01) but negatively correlated with LVEF, LVFS, and CI (r = -0.65, -0.64, and -0.71, respectively; all P < 0.01). BNP concentration was also negatively correlated with LVEF, LVFS, and CI (r = -0.75, -0.61, and -0.79, respectively; all P<0.01). After treatment with carvedilol, the serum concentrations of h-FABP and BNP in group A were lower than in group B, and the magnitude of heart rate reduction, improvement of LVEF, LVFS, and CI, and reduction of left ventricular end-systolic diameter and left ventricular end-diastolic diameter in group A were all greater than in group B (all P < 0.01). Treatment with carvedilol had no adverse events. CONCLUSIONS: Serum concentrations of h-FABP and BNP can be used as biomarkers to evaluate the severity of heart failure, and carvedilol can significantly improve heart function in children with CHF.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Carbazoles/therapeutic use , Fatty Acid-Binding Proteins/blood , Heart Failure/drug therapy , Natriuretic Peptide, Brain/blood , Propanolamines/therapeutic use , Ventricular Function, Left/drug effects , Adrenergic beta-Antagonists/adverse effects , Age Factors , Biomarkers/blood , Carbazoles/adverse effects , Carvedilol , Child , Child, Preschool , China , Chronic Disease , Echocardiography , Enzyme-Linked Immunosorbent Assay , Fatty Acid Binding Protein 3 , Female , Heart Failure/blood , Heart Failure/diagnosis , Heart Failure/physiopathology , Humans , Infant , Male , Myocardial Contraction/drug effects , Predictive Value of Tests , Propanolamines/adverse effects , Severity of Illness Index , Stroke Volume/drug effects , Treatment Outcome
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 15(2): 99-101, 2013 Feb.
Article in Chinese | MEDLINE | ID: mdl-23428121

ABSTRACT

OBJECTIVE: To study serum levels of heart-type fatty acid-binding protein (h-FABP) in children with chronic heart failure (CHF), and the correlation between heart function and the level of h-FABP, with the aim of studying the significance of h-FABP in CHF. METHODS: Thirty-six children with CHF, including 16 cases of endocardial fibroelastosis (EFE) and 20 cases of dilated cardiomyopathy (DCM) were enrolled in the study. Thirty healthy children sevred as the control group. Serum levels of h-FABP were determined using ELISA, and left ventricular ejection fraction (LVEF), cardiac index (CI) and fractional shortening of the left ventricle (LVSF) were measured by two-dimensional echocardiography in the CHF group. RESULTS: Mean levels of h-FABP in the CHF group were significantly higher than in the control group (21.7±4.3 ng/mL vs 6.2±1.7 ng/mL; P<0.01). The worse the heart function, the higher the h-FABP levels (P<0.01). Mean levels of h-FABP in both the EFE and DCM groups were significantly higher than in the control group (P<0.01). Serum h-FABP concentrations were negatively correlated with LVEF, CI and LVSF (r=-0.65, -0.64 and -0.71 respectively; P<0.01) in the CHF group. CONCLUSIONS: Serum h-FABP levels increase in children with CHF and are closely related to the severity of the condition. Serum h-FABP levels can be used as a biomarker for the diagnosis of heart failure and the evaluation of its severity.


Subject(s)
Fatty Acid-Binding Proteins/blood , Heart Failure/blood , Cardiomyopathy, Dilated/blood , Child , Child, Preschool , Chronic Disease , Endocardial Fibroelastosis/blood , Fatty Acid Binding Protein 3 , Female , Heart Failure/physiopathology , Humans , Infant , Male , Severity of Illness Index
19.
Article in Chinese | MEDLINE | ID: mdl-22338229

ABSTRACT

OBJECTIVE: To discuss the epidemiological and clinical characteristics of the hospitalized children with hand foot and mouth disease (HFMD) in Yantai area. METHODS: Epidemiological and clinical data of HFMD children from 2009 to 2010 were summarized and analyzed retrospectively. RESULTS: Most of the infected (94.6%) were under 5 years old and the ratio between male and female was 1.5: 1. Oral mucosal pox or ulcer as well as hand and foot rashes were observed in all 931 patients. Fever and neurological disorders occurred in 840 (90.2%) and 121 (13.0%) patients respectively. The incidence was positively correlated with air temperature (r = 0.887, P < 0.001), with a peak in April to September (88.9%). The ratio of children from countryside, total duration of fever, serum concentration of c-reacting protein (CRP) and fasting blood glucose (FBG) were significantly higher in severe cases than in those mild ones. Multivariate analysis showed longer mean duration of fever( Odds ratio [OR], 1.491; 95% confidence interval [ CI] 1.170-1.901; P = 0.001) and hyperglycemia (OR, 1.124; 95% CI 1.016-1.245; P = 0.024) were independent risk factors of severity. CONCLUSION: Children younger than 5 years old are susceptible to HFMD and most cases occur in April to September. The monthly incidence is positively correlated with temperature of that month. Longer duration of fever and hyperglycemia are independent risk factors for severity. Most cases could have a favorable prognosis after timely diagnosis and proper intervention.


Subject(s)
Hand, Foot and Mouth Disease/epidemiology , Adolescent , Child , Child, Preschool , China/epidemiology , Epidemiologic Studies , Female , Humans , Incidence , Infant , Male , Retrospective Studies , Seasons , Temperature
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