Design and In Vivo Verification of a CMOS Bone-Guided Cochlear Implant Microsystem.

OBJECTIVE: To develop and verify a CMOS bone-guided cochlear implant (BGCI) microsystem with electrodes placed on the bone surface of the cochlea and the outside of round window for treating high-frequency hearing loss. METHODS: The BGCI microsystem consists of an external unit and an implanted unit. The external system-on-chip is designed to process acoustic signals through an acquisition circuit and an acoustic DSP processor to generate stimulation patterns and commands that are transmitted to the implanted unit through a 13.56 MHz wireless power and bidirectional data telemetry. In the wireless power telemetry, a voltage doubler/tripler (2X/3X) active rectifier is used to enhance the power conversion efficiency and generate 2 and 3 V output voltages. In the wireless data telemetry, phase-locked loop based binary phase-shift keying and load-shift keying modulators/demodulators are adopted for the downlink and uplink data through high-Q coils, respectively. The implanted chip with four-channel high-voltage-tolerant stimulator generates biphasic stimulation currents up to 800 µA. RESULTS: Electrical tests on the fabricated BGCI microsystem have been performed to verify the chip functions. The in vivo animal tests in guinea pigs have shown the evoked third wave of electrically evoked auditory brainstem response waveforms. It is verified that auditory nerves can be successfully stimulated and acoustic hearing can be partially preserved. CONCLUSION AND SIGNIFICANCE: Different from traditional cochlear implants, the proposed BGCI microsystem is less invasive, preserves partially acoustic hearing, and provides an effective alternative for treating high-frequency hearing loss.

Regulated and Functional Expression of the Corepressor MTA3 in Rodent Testis.

Metastasis-associated protein (MTA)3 is a subunit of the Mi-2/nucleosome remodeling and deacetylase protein complex, with relevant roles in the regulation of cancerous epithelial to mesenchymal transition in an estrogen-dependent manner, recently involved in the modulation of different physiological processes. Although these findings connect MTA3 expression with hormonal signaling in various systems, little is known about whether this relationship is conserved in testis where hormonal action is intensive. We, therefore, document here for the first time the expression of Mta3/MTA3 in mammalian testes, where MTA3 protein was identified mainly in interstitial Leydig cells. Testicular levels of Mta3/MTA3 were overtly modulated by pituitary gonadotropins, as well as metabolic signals, such as dexamethasone, T4, and rosiglitazone. In addition, ablation of endogenous Mta3 by short hairpin RNA significantly inhibited human choriogonadotropin/dibutyryl-cAMP (db-cAMP)-stimulated progesterone secretion in MA-10 Leydig cells, whereas overexpression of exogenous MTA3 effectively reversed Mta3 deficiency damaged progesterone production. Moreover, attenuated Mta3 expression positively correlated to the deregulated level of serum testosterone in murine type 2 diabetes mellitus. From a functional standpoint, MTA3 deficiency was involved in insulin-mediated inhibition of testicular steroidogenesis. Our data are the first to disclose the presence and functional role of MTA3 in the testis, where its expression is regulated by developmental, metabolic, and hormonal cues and is closely associated with steroidogenic dysfunction. The current study expands the reproductive dimension of MTA3, which may operate directly at the testicular level to modulate steroidogenic function.

Effects of Sevoflurane Inhalation During Cardiopulmonary Bypass on Pediatric Patients: A Randomized Controlled Clinical Trial.

The effects of sevoflurane inhalation during cardiopulmonary bypass (CPB) on postoperative courses and serum cardiac troponin I (cTnI) concentrations in pediatric patients undergoing cardiac surgery have not been extensively investigated. In this single-center, prospective, randomized trial, an anesthetic regimen containing 2% sevoflurane used throughout the CPB process was compared with a total intravenous anesthesia (TIVA) regimen. One hundred and three patients undergoing congenital heart defect repair with CPB were included in this prospective randomized controlled study. They were randomized into two groups: the sevoflurane group, who received 2% sevoflurane during CPB via an oxygenator, and the control group, who received only an oxygen-air mixture. The pre- and intra-operative parameters were comparable between the two groups. There was a slight but significant increase of arterial diastolic pressure in the sevoflurane group immediately after CPB compared with control patients (46.9 ± 9.3 mm Hg vs. 43.6 ± 8.9 mm Hg; p = 0.033). There was no death in either group. The postoperative ventilation time (in mean [95% confidence interval]) was shorter in the sevoflurane group than that in the control group (26.1 [19.2, 33.0] h vs. 37.7 [24.4, 50.9] h; p = 0.014). The postoperative ICU time, hospital days, and serial serum cTnI concentrations were not significantly different between the two groups. Inhalation of 2% sevoflurane during CPB is beneficial to the recovery of pediatric patients undergoing cardiac surgery but has no significant effect on postoperative cTnI release.

Surgical correction of anomalous origin of one pulmonary artery without grafts in infants.

OBJECTIVE: To review the experiences in repairing the anomalous origin of one pulmonary artery in infants. METHODS: From March 2005 to May 2010, 11 infants diagnosed with anomalous origin of one pulmonary artery underwent surgical treatment. Their mean age was 12.7 months (two months to three years), and their mean body weight was 7.1 kg (4 to 13 kg). Seven patients had anomalous origin of the right pulmonary artery, and four patients had anomalous origin of the left pulmonary artery. All 11 patients had an intracardiac anomaly or vascular malformations as well as pulmonary hypertension. A median sternotomy and cardiopulmonary bypass (CPB) were used in all 11 patients. The mean follow-up was 20.5 months (6 to 60 months). RESULTS: The operation time was 169 to 293 min (231 ± 55 min), the CPB time was 87 to 210 min (138 ± 47 min), and the aortic cross-clamp time was 45 to 133 min (86 ± 28 min). There was one hospital death (mortality 9%) in a patient with tetralogy of Fallot who had low cardiac output after the operation. In all cases, there was no application of artificial or homologous grafts. All surviving patients had satisfactory early to midterm results except for one patient with mild pulmonary stenosis. CONCLUSION: The surgical correction of anomalous origin of one pulmonary artery without artificial or homologous grafts has satisfactory early to midterm results in infants.

Acute hyperglycaemia enhances oxidative stress and aggravates myocardial ischaemia/reperfusion injury: role of thioredoxin-interacting protein.

Hyperglycaemia during acute myocardial infarction is common and associated with increased mortality. Thioredoxin-interacting protein (Txnip) is a modulator of cellular redox state and contributes to cell apoptosis. This study aimed to investigate whether or not hyperglycaemia enhances Txnip expression in myocardial ischaemia/reperfusion (MI/R) and consequently exacerbates MI/R injury. Rats were subjected to 30 min. of left coronary artery ligation followed by 4 hrs of reperfusion and treated with saline or high glucose (HG, 500 g/l, 4 ml/kg/h intravenously). In vitro study was performed on cultured rat cardiomyocytes subjected to simulated ischaemia/reperfusion (SI/R) and incubated with HG (25 mM) or normal glucose (5.6 mM) medium. In vivo HG infusion during MI/R significantly impaired cardiac function, aggravated myocardial injury and increased cardiac oxidative stress. Meanwhile, Txnip expression was enhanced whereas thioredoxin activity was inhibited following HG treatment in ischaemia/reperfusion (I/R) hearts. In addition, HG activated p38 MAPK and inhibited Akt in I/R hearts. In cultured cardiomyocytes subjected to SI/R, HG incubation stimulated Txnip expression and reduced thioredoxin activity. Overexpression of Txnip enhanced HG-induced superoxide generation and aggravated cardiomyocyte apoptosis, whereas Txnip RNAi significantly blunted the deleterious effects of HG. Moreover, inhibition of p38 MAPK or activation of Akt markedly blocked HG-induced Txnip expression in I/R cardiomyocytes. Most importantly, intramyocardial injection of Txnip siRNA markedly decreased Txnip expression and alleviated MI/R injury in HG-treated rats. Hyperglycaemia enhances myocardial Txnip expression, possibly through reciprocally modulating p38 MAPK and Akt activation, leading to aggravated oxidative stress and subsequently, amplification of cardiac injury following MI/R.

The myocardial protective effects of a moderate-potassium blood cardioplegia in pediatric cardiac surgery: a randomized controlled trial.

BACKGROUND: We investigated the myocardial protective effect of a moderate-potassium cold blood cardioplegic solution (K+, 10 mmol/L) in pediatric cardiac surgery. METHODS: Sixty-eight pediatric patients with congenital heart disease and undergoing open heart surgery with cardiopulmonary bypass were randomly allocated to the high potassium (HP [K+, 20 mmol/L, n=31]) cold blood cardioplegia group or the moderate potassium (MP [K+, 10 mmol/L, n=37]) cold blood cardioplegia group. Heart arresting time, rhythm recovery time, mechanical ventilation time, inotropic drug use in the intensive care unit, perioperative serum cardiac troponin I concentrations, morbidities, and mortalities were compared between the two groups. RESULTS: There were no differences in cardiopulmonary bypass time, aorta cross-clamping time, cardioplegia volume, lowest body temperature during cardiopulmonary bypass, total volume of cardioplegia delivered, hematocrit value, and fluid output during the operation between the two groups. However, there was a longer arresting time and a shorter rhythm recovery time in the MP group (35.6±2.4 s, and 30.8±3.1 s) when compared with that in the HP group (24.7±2.7 s, and 42.0±4.0 s, both p<0.05). The total mediastinal drainage volume, the length of stay in the intensive care unit, the postoperative inotropic drug use, and the postoperative hospital time were similar between the two groups, but the number of patients with a long postoperative mechanical ventilation time (>24 hours) in the MP group (6 of 36) was less than that in HP group (13 of 30; p<0.05). At 1 hour, 3 hours, and 6 hours after myocardium reperfusion, the serum concentration of cardiac troponin I significantly decreased in the MP group (in ng/mL: 15.18±3.57, 24.83±4.91, and 19.62±3.93, respectively) when compared with that in the HP group (in ng/mL: 32.67±5.31, 39.26±7.43, and 30.52±5.17, respectively, p<0.05). CONCLUSIONS: The present study demonstrated that the M (10 mmol/L) cold blood cardioplegia formula is associated with better myocardial protective effects when compared with conventional HP cardioplegia in pediatric patients.

Different neuroprotection and therapeutic time windows by two specific diazepam regimens on retinal ganglion cells after optic nerve transection in adult rats.

PURPOSE: To compare neuroprotection and therapeutic time windows of two diazepam regimens on retinal ganglion cells (RGCs) after rat optic nerve transection (ONT). METHODS: Adult rats received initial intraperitoneal diazepam injections 30 minutes before left ONT, followed by daily diazepam (regimen-A) or every 8 hours for 3 days (regimen-B) until they were killed at day 7 or 14. Initial diazepam in regimen-A and regimen-B was delayed to 3, 6, 7, 9, 10, 12 and 6, 7, 8, 9, 10, 12 hours after ONT and these animals survived for 7 days. The effect of daily combinational uses of diazepam and bicuculline was assayed at 7 days. RESULTS: Regimen-A induced higher RGC densities than those in control and regimen-B groups at day 7, but lower density than regimen-B did at day 14. When initial diazepam was delayed beyond 6 or 8 hours after ONT with regimen-A and regimen-B, the promoting effects of diazepam on RGC densities disappeared. Bicuculline completely inhibited the protection of diazepam. CONCLUSIONS: Prolonged neuroprotection on RGCs at day 14 and extended therapeutic time window for 8 hours can be achieved by regimen-B, while regimen-A induces a stronger neuroprotection at day 7. Diazepam neuroprotection is mediated through GABAA receptor.

[Gene expression of Notch1 and Jagged1 in children with acute leukemia].

OBJECTIVE: To study the gene expression of Notch1 and Jagged1 in children with acute leukemia (AL) and their possible roles in the pathogenesis of AL. METHODS: Mononuclear cells from bone marrow or peripheral blood of 47 children with AL and 20 controls (normal children or children with nonmalignant hematologic disease) were collected from February 2009 to July 2011. A two-step method to semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the gene expression of Notch1 and Jagged1. Of the 47 children with AL, there were 26 cases of B-ALL, 6 cases of T-ALL and 15 cases of AML. RESULTS: The positive expression rate of Notch1 in the ALL and AML groups was higher than in the control group (P<0.05). The expression level of Notch1 in T-ALL children was higher than in B-ALL children (P<0.01). The positive expression rate of Jagged1 in the ALL and AML groups was not significantly different from the control group, however, the expression level of Jagged1 in the ALL and AML groups was higher than in the control group (P<0.05). CONCLUSIONS: There are significant differences in the gene expression of Notch1 between children with different types of ALL, and a higher expression of Notch1 relates to T-ALL. The activation of Notch1 signal is common in children with AL. The abnormal gene expression of Notch1 in children with AML shows the role of Notch1 in AML. The gene expression of Jagged1 in children with ALL or AML is abnormal, and this needs to be confirmed by further research.

Notch1 signaling pathway participates in cancer invasion by regulating MMPs in lingual squamous cell carcinoma.

Some studies show the Notch signaling pathway may participate in carcinoma invasion and metastasis. However, the mechanisms by which Notch1 mediates cell invasion and migration, especially in lingual squamous cell carcinoma, are not yet known. In the current study, we demonstrated for the first time the anti-invasion and anti-metastasis effect of down-regulation of Notch1 in lingual squamous cell carcinoma. Down-regulation of Notch1 could be an effective approach for inhibition of the expression of matrix metalloproteinase (MMP)-2 and MMP-9 resulting in the inhibition of invasion and metastasis, which could be useful for devising novel preventive and therapeutic strategies for lingual squamous cell carcinoma.

[Expression of cdx2 gene in pediatric patients with leukemia and its clinical significance].

This study was aimed to investigate the expression of cdx2 gene in pediatric patients with acute leukemia and its clinical implication. The bone marrow and peripheral blood were collected from 33 newly diagnosed pediatric patients with acute leukemia, the cdx2 gene expression in each AL subtypes and normal controls was detected by RT-PCR, the relationship between cdx2 expression and response to treatment was observed. The results showed that the expression of cdx2 was positive in 25 out of 30 AL cases (83.3%), to be exact, in 20 of 21 ALL cases (95.2%) and in 5 of 9 AML cases (55.6%), which showed statistical difference (p < 0.05). The cdx2 mRNA could be detected also in 1 of 3 CML cases. However, no expression of cdx2 was observed in all normal control which revealed significant difference between patient group and normal control group. 21 AL patients with cdx2 positive expression (17 ALL and 4 AML patients) and 4 AL patients with cxd2 negative expression (1 ALL and 3 AML patients) all reached complete remission (CR) after treatment, which showed no correlation with CR rate. 8 patients with positive cdx2 expression were followed up. As a result, the cdx2 positive expression at initial diagnosis of patients remained positive at reaching CR, but it gradually turned to negative along with prolonging of CR, while the cdx2 negative expression at initial diagnosis of patients remained negative at CR in bone marrow level. It is concluded that cdx2 positive expression is observed in the majority of pediatric AL patients, even positive rate in ALL patients is higher than that in AML patients, while the cdx2 expression also can be observed in CML patients. The cdx2 positive expression is not related to the CR rate in AL patients.

Evidence for heterogeneity of astrocyte de-differentiation in vitro: astrocytes transform into intermediate precursor cells following induction of ACM from scratch-insulted astrocytes.

Our previous study definitely demonstrated that the mature astrocytes could undergo a de-differentiation process and further transform into pluripotential neural stem cells (NSCs), which might well arise from the effect of diffusible factors released from scratch-insulted astrocytes. However, these neurospheres passaged from one neurosphere-derived from de-differentiated astrocytes possessed a completely distinct characteristic in the differentiation behavior, namely heterogeneity of differentiation. The heterogeneity in cell differentiation has become a crucial but elusive issue. In this study, we show that purified astrocytes could de-differentiate into intermediate precursor cells (IPCs) with addition of scratch-insulted astrocyte-conditioned medium (ACM) to the culture, which can express NG2 and A2B5, the IPCs markers. Apart from the number of NG2(+) and A2B5(+) cells, the percentage of proliferative cells as labeled with BrdU progressively increased with prolonged culture period ranging from 1 to 10 days. Meanwhile, the protein level of A2B5 in cells also increased significantly. These results revealed that not all astrocytes could de-differentiate fully into NSCs directly when induced by ACM, rather they generated intermediate or more restricted precursor cells that might undergo progressive de-differentiation to generate NSCs.

[Genetic diversity of human Parvovirus B19 VP1 unique region].

OBJECTIVE: Human Parvovirus B19 (HPV B19) is a small (23 nm), non-enveloped DNA virus found in 1974. It has been proved that HPV B19 is associated with a variety of childhood diseases, such as erythema infectious, transient aplastic crisis, aplastic anemia, idiopathic thrombocytopenic purpura and arthropathy, etc. There have been no any effective vaccines to prevent HPV B19 infection so far. The HPV B19 genome is composed of 5.6 kb single strand DNA. This genome encodes a nonstructural protein NS1, two structural proteins VP1 and VP2. Most neutralizing linear epitopes of HPV B19 cluster in the VP1 unique and VP1-VP2 junction regions. Only proteins encoded by genes of the VP1 unique and VP1-VP2 junction regions can stimulate bodies to produce protective antibodies. Aim of the present study was to get the VP1 unique region gene of HPV B19 and to analyze the genetic diversity so as to further study its function and application. METHODS: The VP1 unique region gene of HPV B19 was amplified from the serum of a child with idiopathic thrombocytopenic purpura by PCR. The purified PCR product was cloned into pGEM-T easy vector and transfected into the host strain E. coli (DH5 alpha). Positive clones were chosen and then the target gene was sequenced. RESULTS: The target gene sequence of HPV B19 VP1 unique region was amplified and cloned successfully. It had 705 nucleotides. Compared with the relevant sequences published in Genbank, the sequencing results were revealed with two nucleotides changes in the HPV B19 VP1 unique region, but their coding amino acid were not changed. CONCLUSION: It is suggested that genetic diversity exists in the VP1 unique region of HPV B19. Construction of the recombinant plasmid of HPV B19 VP1 unique region gene might benefit to further study.