Endothelialization of PTFE-covered stents for aneurysms and arteriovenous fistulas created in canine carotid arteries.

To investigate the endothelialization of covered and bare stents deployed in the canine carotid arteries and subclavian arteries for treating experimental aneurysms and arteriovenous fistulas, twenty aneurysms were created in 10 dogs, and 20 fistulas in another 10 dogs. The Willis balloon-expandable covered stent and a self-expandable covered stent were used to treat these lesions, and a self-expandable bare stent was deployed in the subclavian artery for comparison. Followed up for up to 12 months, the gross observation, pathological staining, and scanning electronic microscopic data were analyzed. Two weeks after creation of animal model, thirty self-expandable covered stents and ten balloon-expandable covered stents were deployed. Fifteen bare stents were deployed within the left subclavian arteries. Twenty days after stenting, the aneurysm significantly shrank. At 6 months, the thrombi within the aneurysm cavity were organized. Three to 12 months later, most covered and bare stents were covered by a thin transparent or white layer of endothelial intima. Layers of intima or pseudomembrane were formed on the stent 20-40 days after stent deployment. Over three months, the pseudomembrane became organized, thinner, and merged into the vascular wall. Under scanning electronic microscopy, the surface of covered and bare stents had only deposition of collagen fibers and rare endothelial cells 20-40 days after stenting. From three to ten months, the endothelial cells on the internal surface of stent became mature, with spindle, stripe-like or quasi round morphology along the blood flow direction. Over time, the endothelial cells became mature. In conclusion, three months after deployment in canines' arteries, the self-expandable bare and covered stents have mostly been covered by endothelial cells which become maturer over time, whereas the balloon-expandable covered stents do not have complete coverage of endothelial cells at three months, especially for protruding stent struts and areas. Over time, the endothelialization will become mature.

Risk factors for instent restenosis of sirolimus-coated stents in coronary intervention for patients with unstable angina.

To investigate the instent restenosis rate of sirolimus-coated stents in percutaneous coronary intervention (PCI) and risk factors for in-stent restenosis, patients with unstable angina (UA) caused by coronary artery stenosis were enrolled, and all clinical and imaging data were analyzed. Among 143 enrolled patients with UA aged 35-83 (mean 60.9 ± 10.0) years enrolled, there were 114 (79.7%) male and 29 (20.3%) female patients. Arterial stenosis was present in one coronary artery in 6 (4.2%) patients, in two coronary arteries in 20 (14.0%) patients, in three arteries in 116 (81.1%), and in four coronary arteries in 1 (0.7%) patient. Stenting was successfully performed in all (100%) patients, and 181 stents were deployed. The quantitative flow ratio (QFR) was 0.92 ± 0.03 (range 0.84-0.96) immediately after stenting, and the TIMI was grade 3 in all patients. The diameter of the stents deployed ranged 2.25-4 mm (mean 3.04 ± 0.44) with a length ranging 10 mm to 104 mm (mean 32.73 ± 15.5). Follow-up angiography was performed in all patients with a duration of 1-92 (mean 15.0 ± 18.8) months. Instent restenosis ≥ 50% occurred in 25 (17.5%) patients. In univariate logistic regression analysis, significant (P < 0.05) risk factors for instent restenosis ≥ 50% were QFR (OR 0.036, 95% CI 0.13-0.97), stent diameter (OR 0.43, 95% CI 0.18-0.92), hypertension (OR 3.16, 95% CI 1.02-9.82), smoking (OR 0.31, 95% CI 0.11-0.89), and neutrophil count (OR 2.22, 95% CI 1.10-5.44). In multivariate analysis, QFR (OR 0.02, 95% CI 0.002-0.19), stent diameter (OR 0.06, 95% CI 0.005-0.59), hypertension (OR 6.75, 95% CI 1.83-35.72) and neutrophil count (OR 276.07, 95% CI 12.32-10,959.95) were significant (P < 0.05) independent risk factors for instent restenosis ≥ 50%. In conclusion, certain instent restenosis rates occurs after the sirolimus-eluted coronary stent deployment for the treatment of coronary artery stenosis in patients with UA, and quantitative flow ratio after stenting, stent diameter, hypertension, and neutrophil count are significant risk factors for instent restenosis of the sirolimus-coated stents in coronary intervention.

Complications and long-term in-stent restenosis of endovascular treatment of severe symptomatic intracranial atherosclerotic stenosis and relevant risk factors.

To investigate the complications and in-stent restenosis of endovascular treatment of severe symptomatic intracranial atherosclerotic stenosis and relevant risk factors. Three hundred and fifty-four consecutive patients with intracranial atherosclerotic stenosis (70%-99%) were retrospectively enrolled. The clinical data, treatment outcomes, complications and in-stent restenosis at follow-up were analyzed. The endovascular treatment was composed of balloon dilatation only in 21 (5.93%) patients, and deployment of self-expandable stents in 232 (65.54%), balloon-expandable stents in 75 (21.19%), and both balloon- and self-expandable stents in 26 (7.34%), with a total of 359 stents being successfully deployed at the stenotic location. After treatment, the residual stenosis ranged 9.2%±1.5% (range 7%-19%), which was significantly (P < .05) smaller than that before treatment. Periprocedural complications occurred in 43 patients with a complication rate of 12.15% including arterial dissection in 4 (1.13%) patients, new cerebral infarction in 21 (5.93%), cerebral hemorrhage in 12 (3.3%), and subarachnoid hemorrhage in 6 (1.69%). Hyperlipidemia [odds ratio (OR) 10.35, 95% confidence interval (CI) 4.42-24.28, and P < .0001] and location at the middle cerebral artery (MCA) (OR 4.15, 95% CI 1.92-8.97, and P < .001) were significant (P < .05) risk factors for periprocedural complications, whereas hyperlipidemia (OR 11.28, 95% CI 4.65-30.60, and P < .0001), location at the MCA (or 5.26, 95% CI 2.03-15.08, and P < .001), and angulation (OR 1.02, 95% CI 1.00-1.04, and P = .02) were significant (P < .05) independent risk factors for periprocedural complications. Follow-up was performed in 287 (81.07%) patients at 6 to 36 (28 ± 6.7) months. In-stent restenosis was present in 36 (12.54%), and female sex (OR 2.53, and 95% CI 1.27-5.06) and periprocedural complications (OR 9.18, and 95% CI 3.52-23.96) were significant (P < .05) risk factors for in-stent restenosis, with periprocedural complication (OR 9.61, and 95% CI 3.48-27.23) as the only significant (P < .0001) independent risk factor for in-stent restenosis. A certain rate of periprocedural complications and in-stent stenosis may occur in endovascular treatment of severe intracranial stenosis, and the relevant risk factors may include hyperlipidemia, MCA location, angulation at the stenosis and female sex.

Effects of high-intensity focused ultrasound combined with levonorgestrel-releasing intrauterine system on patients with adenomyosis.

It is very important to treat adenomyosis which may cause infertility, menorrhagia, and dysmenorrhea for women at the reproductive age. High-intensity focused ultrasound (HIFU) is effective in destroying target tumor tissues without damaging the path of the ultrasound beam and surrounding normal tissues. The levonorgestrel-releasing intrauterine system (LN-IUS) is a medical system which is inserted into the uterine to provide medicinal treatment for temporary control of the symptoms caused by adenomyosis. This study was to investigate the effect of HIFU combined with the LN-IUS on adenomyosis. In the HIFU treatment, the parameters of the ultrasound were transmission frequency 0.8 MHz and input power 50-400 W (350 ± 30), and the temperature in the target tissue under these conditions would reach 60-100 °C (85 °C ± 6.3 °C). Size reduction and blood flow signal decrease were used to assess the effect of combined treatment. In this study, 131 patients with adenomyosis treated with HIFU combined with LN-IUS were retrospectively enrolled. The clinical and follow-up data were analyzed. After treatment, the volume of the uterine lesion was significantly decreased with an effective rate of 72.1%, and the adenomyosis blood flow signals were significantly reduced, with an effective rate of 71.3%. At six months, the menstrual cycle was significantly (P < 0.05) decreased from 31.4 ± 3.5 days before treatment to 28.6 ± 1.9 days, the menstrual period was significantly shortened from 7.9 ± 1.2 days before HIFU to 6.5 ± 1.3 days, and the menstrual volume was significantly (P < 0.05) decreased from 100 to 49% ± 13%. The serum hemoglobin significantly (P < 0.05) increased from 90.8 ± 6.2 g/L before treatment to 121.6 ± 10.8 g/L at six months for patients with anemia. Among seventy-two (92.3%) patients who finished the six-month follow-up, sixty-five (90.3%) patients had the dysmenorrhea completely relieved, and the other seven (9.7%) patients had only slight dysmenorrhea which did not affect their daily life. Adverse events occurred in 24 (18.3%) patients without causing severe consequences, including skin burns in two (1.5%) patients, skin swelling in four (3.1%), mild lower abdominal pain and low fever in 15 (11.5%), and subcutaneous induration in three (2.3%). Six months after treatment, no other serious side effects occurred in any patients with follow-up. In conclusions, the use of high-intensity focused ultrasound combined with the levonorgestrel-releasing intrauterine system for the treatment of adenomyosis is safe and effective even though the long-term effect remains to be confirmed.

Decreased AGGF1 facilitates the progression of placenta accreta spectrum via mediating the P53 signaling pathway under the regulation of miR-1296-5p.

Placenta accreta spectrum (PAS), an emerging health issue worldwide, is the major causative factor of maternal morbidity and mortality in modern obstetrics, but limited studies have contributed to our understanding of the molecular biology of PAS. This study addressed the expression of AGGF1 and its specific role in the etiology of PAS. The expression of AGGF1 in the placentas of PAS was determined by quantitative PCR, western blot and immunohistochemistry. CCK-8 assay, wound healing assay, Transwell invasion assay and flow cytometry assay were performed to monitor cell proliferation, migration, invasion and apoptosis. The interaction between miR-1296-5p and AGGF1 was detected by dual-luciferase reporter gene assay. Results showed that the mRNA and protein expression of AGGF1 was decremented in placental tissues of PAS patients, compared with samples from women with placenta previa and normal pregnant women. Downregulation of AGGF1 promoted cell proliferation, invasion and migration, inhibited apoptosis in vitro, decreased P53 and Bax expression, and simultaneously increased Bcl-2 expression, whereas overexpression of AGGF1 had the opposite results. Additionally, the dual-luciferase assay confirmed AGGF1 as a target gene of miR-1296-5p in placental tissues of PAS. Particularly, miR-1296-5p fostered HTR8/SVneo cell proliferation, invasion, repression of apoptosis and regulation of P53 signaling axis by downregulating AGGF1 expression. Collectively, our study accentuated that downregulation of placental AGGF1 promoted trophoblast over-invasion by mediating the P53 signaling pathway under the regulation of miR-1296-5p.

Safety and effects of endovascular treatment of basilar tip aneurysms in patients with moyamoya diseases.

The effect and safety of endovascular treatment of basilar tip aneurysms associated with moyamoya disease are unknown. This study was to investigate the safety and effect of endovascular treatment of basilar tip aneurysms associated with moyamoya disease. Patients with moyamoya disease concurrent with basilar tip aneurysms were retrospectively enrolled and treated with endovascular embolization. The clinical and angiographic data were analyzed. Thirty patients with a basilar tip aneurysm were enrolled, including 8 (26.67%) male and 22 (73.33%) female patients aged 38 to 72 years (mean 54.4 ± 8.15). Endovascular treatment was successfully performed in 29 (96.67%) patients but failed in 1 (3.33%). Immediately after embolization, aneurysm occlusion degree was Raymond-Roy grade I in 26 (89.66%), grade II in 2 (6.90%), and grade III in 1 (3.45%). Intraprocedural complications occurred in 2 (10%) patients, including aneurysm rupture in 1 (3.33%), leading to death of the patient, and stent thrombosis in 2 (6.67%) which was successfully treated with thrombolysis. At discharge, good clinical outcome (modified Rankin Scale 0-2) was achieved in 29 (96.67%) and death in 1 (3.03%). Follow-up was performed 6 to 26 months (median 15) in 27 (93.1%) patients. Aneurysm occlusion degree was Raymond-Roy grade I in 21 (77.78%) patients, grade II in 4 (14.81%), and grade III in 2 (7.41%), not significantly (P = .67) different from those immediately after embolization. Aneurysm recurrence was found in 4 patients (14.81%). The clinical outcome was modified Rankin Scale 0 to 2 in all 27 patients, not significantly different from that at discharge. Endovascular embolization can be performed safely and effectively for basilar tip aneurysms associated with moyamoya disease even though more advanced embolization techniques are necessary.

Epicardial fat volume evaluated with multidetector computed tomography and other risk factors for prevalence of three-vessel coronary lesions.

PURPOSE: To retrospectively investigate the epicardial fat volume with multidetector computed tomography (MDCT) and other risk factors for the prevalence of three-vessel coronary lesion. MATERIALS AND METHODS: MDCT was performed on 424 subjects with or without three-vessel coronary lesion. Blood was tested for triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A (ApoA), apolipoprotein B (ApoB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipoprotein a, and fasting blood glucose. RESULTS: Among all the subjects, a significant (P < 0.05) negative linear correlation existed between age and ALT or ALT/AST. The epicardial fat had a significant (P < 0.05) negative linear correlation with HDL and Apo A but a positive correlation with age and ApoB/ApoA. The epicardial fat volume and the fasting blood glucose were significantly (P = 0.001) greater in the patients than in the control group, whereas HDL and Apo A were both significantly (P < 0.0001) smaller in the patients than in the control groups. A significant prediction value (P < 0.05) existed in age increase, male gender, epicardial fat increase, low HDL, high LDL, and elevated fasting blood glucose. CONCLUSION: Three-vessel coronary lesions are more prevalent in subjects with greater volume of epicardial fat and in male gender.

[A rare case of dicentric ring chromosome and derivative ring chromosome Chimera].

OBJECTIVE: Utilize high-resolution chromosome analysis and microarray detection to determine the genetic etiology of infertility of a 32-year old female patient. METHODS: The peripheral blood of the patient was cultured for high-resolution chromosome G and C banding karyotype analysis, and then 750K SNP-Array chip detection was performed. RESULTS: Karyotype analysis results showed that the patient's karyotype was 45,XX,-13 [7]/46,XX,r(13) (p13q34) [185]/46,XX,dic r(13;13)(p13q34;p13q34) [14]/ 47,XX,+der(13;13;13;13) (p13q34;p13q34;p13q34; p13q34), dic r(13;13) [1]/ 46,XX [3]. The microarray results showed that the patient had a 3.3 Mb deletion in the 13q34 segment of chromosome 13, which may be related to infertility. CONCLUSION: Infertility of the patient reported in this article may be related to the deletion of chromosome segment (13q34-qter).

MiR-383-5p promotes apoptosis of ovarian granulosa cells by targeting CIRP through the PI3K/AKT signaling pathway.

PURPOSE: To detect miR-383-5p and cold-inducible RNA binding protein (CIRBP, CIRP) expression in patients with polycystic ovary syndrome (PCOS) and explore the mechanism underlying their effect on apoptosis in ovarian granulosa cells (GCs). METHODS: GCs were extracted from follicular fluid from 101 patients. MiR-383-5p and CIRP expression were assessed by quantitative real time polymerase chain reaction analysis. Correlation between them was assessed by Spearman correlation analysis. The potential of using miR-383-5p expression for discriminating PCOS and non-PCOS patients was predicted by receiver operating characteristic curve analysis. Proliferation and apoptosis of KGN cells transfected for miR-383-5p overexpression or knockdown was evaluated using cell counting kit-8 assay, flow cytometry, and western blot analysis. CIRP was identified as a direct target of miR-383-5p, and verified by dual-luciferase reporter assay. RESULTS: The expression level of miR-383-5p was decreased and CIRP mRNA was increased in PCOS patients. The expression of miR-383-5p was correlated negatively with body-mass index, basal luteinizing hormone and testosterone levels, luteinizing hormone/follicle-stimulating hormone ratio, and the number of retrieved and metaphase II oocytes. MiR-383-5p had sufficient potential for prediction of PCOS. There was a negative correlation between the expression of miR-383-5p and CIRP. Overexpression of miR-383-5p enhanced the apoptosis of KGN cells. CIRP reversed the effect of miR-383-5p on promotion of apoptosis. MiR-383-5p mimics could suppress the PI3K/AKT signaling pathway, which was activated by the CIRP overexpressing plasmid. CONCLUSIONS: MiR-383-5p promoted apoptosis of ovarian GCs through the PI3K/AKT signaling pathway by targeting CIRP.

[Significance and case analysis of FMR1 mutation screening during early and middle pregnancy].

OBJECTIVE: To screen for mutations of fragile X mental retardation 1 (FMR1) gene during early and middle pregnancy and provide prenatal diagnosis for those carrying high-risk CGG trinucleotide expansions. METHODS: Peripheral blood samples of 2316 pregnant women at 12 to 21(+6) gestational weeks were collected for the extraction of genomic DNA. CGG repeats of the FMR1 gene were detected by fluorescence PCR and capillary electrophoresis. Genetic counseling and prenatal diagnosis were provided for 3 women carrying the premutations. RESULTS: The carrier rate of CGG repeats of the FMR1 gene was 1 in 178 for the intermediate type and 1 in 772 for the premutation types. The highest frequency allele of CGG was 29 repeats, which accounted for 49.29%, followed by 30 repeats (28.56%) and 36 repeats (8.83%). In case 1, the fetus had a karyotype of 45,X, in addition with premutation type of CGG expansion of the FMR1 gene. Following genetic counseling, the couple chose to terminate the pregnancy through induced labor. The numbers of CGG repeats were respectively 70/- and 29/30 for the husband and wife. In case 2, amniocentesis was performed at 20 weeks of gestation. The number of CGG repeats of the FMR1 gene was 29/-. No abnormality was found in the fetal karyotype and chromosomal copy number variations. The couple chose to continue with the pregnancy. Case 3 refused prenatal diagnosis after genetic counseling and gave birth to a girl at full term, who had a birth weight of 2440 g and no obvious abnormality found during follow-up. CONCLUSION: Pregnant women should be screened for FMR1 gene mutations during early and middle pregnancy, and those with high-risk CGG expansions should undergo prenatal diagnosis, genetic counseling and family study.

[Prenatal diagnosis and genetic counseling in two pedigrees affected with infantile polycystic kidney disease due to PKHD1 gene mutations].

OBJECTIVE: To detect potential mutations of the PKHD1 gene in two pedigrees affected with infantile polycystic kidney disease. METHODS: Clinical data and peripheral venous blood samples were collected from the probands and their parents as well as fetal amniotic fluid cells. Genome DNA was extracted from the peripheral blood samples and amniotic fluid cells. Exons 32 and 61 of the PKHD1 gene were amplified with PCR and subjected to direct sequencing. RESULTS: The proband of pedigree 1 was found to carry c.4274T>G (p.Leu1425Arg) mutation in exon 32 and c.10445G>C (p.Arg3482Pro) mutation in exon 61 of the PKHD1 gene, which were inherited from her father and mother, respectively. The fetus has carried the c.4274T>G (p.Leu1425Arg) mutation. In pedigree 2, the wife and her husband had respectively carried a heterozygous c.5979_5981delTGG mutation and a c.9455delA mutation of the PKHD1 gene. No chromosomal aberration was found in the umbilical blood sample, but the genetic testing of their fetus was failed. Based on software prediction, all of the 4 mutations were predicted to be pathogenic. CONCLUSION: PKHD1 c.4274T>G (p.Leu1425Arg), c.10445G>C (p.Arg3482Pro), c.5979_5981delTGG and c.9455delA were likely to be pathogenic mutations. The results have facilitated genetic counseling and prenatal diagnosis for the two pedigrees.

Potential of Punica granatum biochar to adsorb Cu(II) in soil.

Biochar as a promising adsorbent to remove heavy metals has attracted much attention globally. One of the potential adsorbents is biochar derived from punica granatum peels, a growing but often wasted resource in tropical countries. However, the immobilization capacity of punica granatum peel biochar is not known. This study investigated the physicochemical properties of punica granatum peel boichars pyrolyzed at 300 °C and 600 °C (referred as BC300 and BC600), and the efficiency and mechanisms of Cu(II) adsorption of five types of material treatments: BC300, BC600, soil only, and soils with biochar amendment BC300 and BC600, respectively, at the rate of 1% of the soil by weight. The results show that BC300 had higher yield, volatile matter content and organic carbon content, and larger pore diameter, but less ash content, surface area, pH, and cation exchange capacity than BC600. The Cu(II) adsorption capacity onto biochars and soils with biochar were greatly influenced by initial ion concentration and contact time. The Cu(II) adsorption capacity of biochar, independent of pyrolysis temperature, was around 52 mg g-1. The adsorption capacity of the soil amended with biochar nearly doubled (29.85 mg g-1) compared to that of the original soil (14.99 mg g-1), indicating superb synergetic adsorption capacity of the biochar-amended soils. The adsorption isotherms showed monolayer adsorption of Cu(II) on biochar, and co-existence of monolayer and multilayer adsorption in soils with or without biochar amendment. Results also suggest that the adsorption process is spontaneous and endothermic, and the rate-limiting phase of the sorption process is primarily chemical. This study demonstrates punica granatum peel biochar has a great potential as an adsorbent for Cu(II) removal in soil.

Downregulation of microRNA-425-5p suppresses cervical cancer tumorigenesis by targeting AIFM1.

Although microRNA-425-5p (miR-425-5p) has been previously revealed to be upregulated in cervical cancer, the cellular function of miR-425-5p in cervical cancer remains unknown. The aim of the current study was to investigate the cellular function of miR-425-5p and its underlying mechanism in cervical cancer. Reverse transcription-quantitative polymerase chain reaction was used to measure miR-425-5p expression in several cervical cancer cell lines. TargetScan bioinformatics analysis was used to predict apoptosis-inducing factor mitochondria-associated 1 (AIFM1) as a novel target of miR-425-5p, and this was verified by dual-luciferase reporter assay. Furthermore, cell transfections were used to investigate the role of miR-425-5p in cervical cancer. The effect of miR-425-5p on cell viability and apoptosis in HeLa cells was detected by MTT assay and flow cytometry, respectively. The present study demonstrated that miR-425-5p was significantly upregulated in cervical cancer cell lines. In addition, AIFM1 was identified as a direct target of miR-425-5p and negatively regulated by miR-425-5p. Downregulation of miR-425-5p inhibited HeLa cell viability and induced cell apoptosis. Furthermore, downregulation of miR-425-5p significantly increased the protein and mRNA expression levels of cytochrome c, caspase-3, caspase-9 and DNA damage regulated autophagy modulator 1. The effects of miR-425-5p inhibition on HeLa cell viability and apoptosis were significantly reversed by AIFM1 knockdown. In conclusion, the present study demonstrated that miR-425-5p was upregulated in cervical cancer, and downregulation of miR-425-5p inhibited cervical cancer cell growth by targeting AIFM1.

Tanshinone l exhibits anticancer effects in human endometrial carcinoma HEC-1-A cells via mitochondrial mediated apoptosis, cell cycle arrest and inhibition of JAK/STAT signalling pathway.

PURPOSE: Tanshinone I is an important plant-derived natural product that has been reported to exert impressive bioactivities, including antiproliferative effects against different types of cancer cells. In this study the anticancer effects of tanshinone I were examined on human endometrial cancer cells along with its mechanism of anticancer action. METHODS: Antiproliferative activity and apoptosis were investigated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide] and DAPI (4',6-diamidino- 2-phenylindole) staining, respectively. Effects on reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were estimated by flow cytometry and western blotting was performed to examine the effect of tanshinone I on JAK/STAT signalling pathway proteins. RESULTS: The results of this study revealed that tanshinone I inhibited the proliferation of the human endometrial carcinoma HEC-1-A cells in a dose-dependent manner. The IC50 of tanshinone I was 20 µM. The antiproliferative effects were due to induction of apoptosis in human endometrial carcinoma HEC-1-A cells. Tanshinone I also caused increase the ROS levels in these cells which was linked with the reduction the MMP levels. Tanshinone I also modulated the expression of JAK/STAT signalling pathway proteins. CONCLUSION: In conclusion, tanshinone I may prove beneficial in the development of systemic therapy for endometrial carcinoma and deserves further research including its in vivo anticancer effects which shall be our future research work in this project.

Performance of LC/MS/MS in Analyzing Multiple Amino Acids and Acylcarnitines in Dried Blood Spot of Very Low Birth Weight, Low Birth Weight, and Normal Weight Neonates.

BACKGROUND: Amino acid (AA) and acylcarnitine (AC) are important biomarkers of protein and fatty acid metabolism. Examining their levels in newborns may reveal multiple inherited metabolic diseases. However, they have rarely been assessed in very low birth weight (VLBW) neonates, low birth weight (LBW) neonates and rarely been compared with normal weight (NW) neonates. The aim of the study was to identify the AA and AC profiles in dried blood spot (DBS) specimens of LBW and VLBW neonates, then compare with NW neonates, and make a contribution to the determination of cutoff values of VLBW and LBW neonates. METHODS: Liquid Chromatography tandem mass spectrometry (LC/MS/MS) is an excellent tool for quantitatively detecting AA and AC profiles. This article verified the precision, accuracy, and linearity of the LC/MS/MS method in AA and AC detection, then analyzed AA and AC profiles in DBS of VLBW, LBW and NW neonates, and compared the difference of AA and AC in the three groups. RESULTS: The results showed that the LC/MS/MS method had wide linear range, satisfied precision and reproducibility in detecting AA and AC in DBS specimens; most AA and AC concentrations significantly correlated with birth weight in DBS samples (p < 0.05). CONCLUSIONS: The results suggested that VLBW and LBW neonates have different metabolic or nutritional status with NW neonates and different AA and AC cutoffs should be defined for them to reduce the risk of false-positive cases.

Microneedles Integrated with ZnO Quantum-Dot-Capped Mesoporous Bioactive Glasses for Glucose-Mediated Insulin Delivery.

A self-responsive insulin delivery system is highly desirable because of its high sensitivity dependent on blood glucose levels. Herein, a smart pH-triggered and glucose-mediated transdermal delivery system, insulin-loaded and ZnO quantum dots (ZnO QDs) capped mesoporous bioactive glasses (MBGs) integrated with microneedles (MNs), was developed to achieve control and painless administration. ZnO QDs as a promise pH-responsive switch were employed to cap the nanopores of MBGs via electrostatic interaction. The drug (insulin) and glucose-responsive factor (glucose oxidase/catalase, GOx/CAT) were sealed into the pores of MBGs. GOx/CAT in the MBGs could catalyze glucose to form gluconic acid, resulting decrease in the local pH. The ZnO QDs on the surface of the MBGs could be dissolved in the acidic condition, leading to disassembly of the pH-sensitive MBGs and then release of preloaded insulin from the MBGs. As a result of administration in a diabetic model, an excellent hypoglycemic effect and lower hypoglycemia risk were obtained. These results indicate that as-prepared pH-triggered and glucose-mediated transdermal delivery systems have hopeful applications in the treatment of diabetes.

Increased bone morphogenetic protein-6 in follicular fluid and granulosa cells may correlate with fertilization and embryo quality in humans.

Bone morphogenetic protein-6 (BMP-6), which is a member of the transforming growth factor-ß superfamily, is associated with the regulation of bone development and various physiological processes. In the present study, the expression of BMP-6 in follicular fluid and granulosa cells (GCs) from pregnant and non-pregnant patients was explored. A total of 44 pregnant patients (pregnant group) and 36 non-pregnant patients (non-pregnant group) were recruited for the present study. The expression of BMP-6 was detected using western blotting and reverse transcription-quantitative polymerase chain reaction. The expression of BMP-6 was significantly higher at the protein level (P<0.01) in follicular fluid obtained from the pregnant group compared with that from the non-pregnant group. The mRNA and protein expression of BMP-6 in GCs were significantly upregulated in the pregnant group compared with the non-pregnant group (both P<0.01). These results suggest that high expression of BMP-6 in pregnant women may be a novel biomarker for the fertility process.

[Identification of a novel SLC26A4 mutation in a child with enlarge vestibular aqueduct syndrome].

OBJECTIVE: To analyze mutations of SLC26A4 gene and explore their origins for a patient with enlarge vestibuar aqueduct syndrome. METHODS: Clinical data and peripheral venous blood samples were collected from the patient and her parents. Genome DNA was extracted from the peripheral blood. All of the 21 exons of the SLC26A4 gene were amplified with PCR and subjected to directly sequencing. RESULTS: The patient was found to have carried two mutant alleles of the SLC26A4 gene, namely c.1522A to G and c.1229C to T, which were inherited from her father and mother, respectively. CONCLUSION: SLC26A4 c.1522A to G is likely to be a pathogenic mutation. Above results may facilitate genetic counseling and prenatal diagnosis for this family.

Association of Vasculogenic Mimicry Formation and CD133 Expression with Poor Prognosis in Ovarian Cancer.

AIMS: This study was conducted to investigate the association of vasculogenic mimicry (VM) formation and CD133 expression with the clinical outcomes of patients with ovarian cancer. METHODS: This retrospective study was performed in 120 ovarian carcinoma samples. VM formation and CD133 expression was identified with CD31/periodic acid-Schiff double-staining and CD133 immunohistochemical staining. Collected clinical and pathological data included age at diagnosis, histologic type, tumor grade, tumor stage, lymph node metastases and response to chemotherapy. The overall survival time was calculated. RESULTS: VM was identified in 52 (43%) of 120 ovarian carcinoma tissues and CD133 expression was found in 56 (47%) cases. Both VM formation and CD133 expression were associated with advanced tumor stage, high-grade carcinoma and non-response to chemotherapy (p < 0.05). They were also associated with shorter overall survival time (p < 0.05) by log-rank test. Combined marker of VM formation and CD133 expression was associated with high-grade ovarian carcinoma, late-stage disease, non-response to chemotherapy and shorter overall survival time (p < 0.05). CONCLUSIONS: VM formation and CD133 expression can provide additional prognostic information for patients with ovarian cancer. Combined marker of VM formation and CD133 expression may be a potent predictor for poor prognosis for patients with ovarian cancer.

A study of deafness-related genetic mutations as a basis for strategies to prevent hereditary hearing loss in Hebei, China.

Hearing loss is the most common sensory disorder, and at least 50% of cases are due to a genetic etiology. Two-thirds of individuals with congenital deafness are nonsyndromic. Among the nonsyndromic forms, the large majority are monogenic autosomal recessive traits. The current work summarizes mutations in the GJB2, SLC26A4, 12SrRNA, and GJB3 and their prevalence in 318 students with autosomal recessive nonsyndromic hearing loss at schools for the deaf or special needs schools in 9 cities in Hebei Province, China. Deafness gene mutations were identified in 137 students via a gene chip, time-of-flight mass spectrometry, fluorescence quantitative PCR, and gene sequencing. Mutations were detected at a rate of 43.08%. A homozygous mutation of the GJB2 gene was found in 16 students (5.03%), a heterozygous mutation of that gene was found in 38 (11.95%), a homozygous mutation of the SLC26A4 gene was found in 22 (6.92%), a heterozygous mutation of that gene was found in 59 (18.55%), and a heterozygous mutation of the mitochondrial 12SrRNA gene was found in 2 (0.63%). In addition, there were 15 families in which a student's parents had normal hearing. Compound heterozygous mutations of the GJB2 gene were found in 3 families (20%) and mutations of the SLC26A4 gene were found in 9 (60%). Thus, this study has provided a molecular diagnostic basis for the causes of deafness, and this study has also provided a scientific basis for the early prevention of and intervention in deafness.