[Efficiency of electrocardiogram monitor for positioning the catheter tip in the central catheter placement via lower extremity veins in neonates: a randomized controlled study]. / å¿ƒç”µç›‘æŠ¤ä»ªåœ¨æ–°ç”Ÿå„¿ç»ä¸‹è‚¢é™è„‰ç½®å ¥ä¸­å¿ƒé™è„‰å¯¼ç®¡ä¸­å®šä½æ•ˆæžœçš„éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the efficiency of electrocardiogram (ECG) monitor for positioning the catheter tip in the placement of peripherally inserted central venous catheterization (PICC) via lower extremity veins in neonates. METHODS: A total of 120 neonates who were admitted to the neonatal intensive care unit from January 2020 to January 2022 and received PICC via lower extremity veins were enrolled and divided into a control group and an observation group using a random number table (n=60 each). The neonates in the control group were given body surface measurement and postoperative chest X-ray localization, and those in the observation group were given body surface measurement, ECG-guided positioning, and postoperative chest X-ray localization. The two groups were compared in terms of general information, one-time success rate of PICC placement, and time spent on PICC placement, and the efficiency of ECG-guided positioning was evaluated. RESULTS: Compared with the control group, the observation group had a higher one-time success rate of PICC placement (92% vs 75%; P<0.05) and a shorter time spent on PICC placement [(26.5±3.0) min vs (31.8±2.8) min; P<0.05]. ECG-guided positioning had a sensitivity of 90.9% and a specificity of 100% in the PICC placement via lower extremity veins in neonates. CONCLUSIONS: ECG monitor helps to determine the position of catheter tip in the PICC placement via lower extremity veins in neonates and can improve the one-time success rate of PICC placement and reduce the time spent on PICC placement, with a good positioning efficiency.

[RCT of Reduction in Catheter-Related Complications by Using Intracavitary Electrocardiogram-Assisted Guidance in Neonatal PICC Placement].

OBJECTIVE: To investigate the effect of intracavitary electrocardiogram (IC-ECG) guidance on peripherally inserted central catheter (PICC) related complications in neonatal patients. METHODS: A total of 210 neonatal patients were included in the study. They were admitted to the Neonatal Intensive Care Unit, Sichuan Provincial People's Hosptial between January, 2017 and December, 2019 and had PICC lines were placed in their upper limbs. The patients were randomly assigned to the observation group, which had PICC placement through conventional anatomical landmark guidance combined with IC-ECG guidance ( n=105) or to the control group, which had PICC placement through only conventional anatomical landmark guidance ( n=105) for PICC catheter tip positioning. Patient baseline data and data on subsequent catheter-related complications of the two groups were collected and compared. RESULTS: There were no significant difference between the two groups in sex composition, gestational age, postnatal days on the day of PICC placement, duration of PICC placement, disease profile, and the site of puncture ( P>0.05). The observation group showed a significantly lower overall incidence of catheter-related complications (3.8%), compared to that of the control group (21.9%) ( P<0.05). The observation group showed significantly lower incidence of phlebitis and arrhthmia compared to that of the control group ( P<0.05). CONCLUSION: A combination of anatomical landmark guidance and IC-ECG guidance to assist the placement of PICC decreases catheter-related complications.

An interpretation of "congenital hypothyroidism: a 2020-2021 consensus guidelines update-an ENDO-European Reference Network initiative endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology". / 《2020~2021å¹´æ¬§æ´²å† åˆ†æ³Œå‚è€ƒç½‘å ±è¯†æŒ‡å—ï¼šå ˆå¤©æ€§ç”²çŠ¶è ºåŠŸèƒ½å‡ä½Žç—‡ã€‹è§£è¯».

Congenital hypothyroidism is one of the common diseases causing delayed intelligence development and growth retardation in children. In 2021, the ENDO-European Reference Network updated the practice guidelines for the diagnosis and management of congenital hypothyroidism. The guidelines give a comprehensive and detailed description of the screening, diagnosis, and management of congenital hypothyroidism in neonates. This article gives an interpretation of the guidelines in order to provide a reference for clinicians in China.

Accuracy and Safety Study of Intracavitary Electrocardiographic Guidance for Peripherally Inserted Central Catheter Placement in Neonates.

The purpose of this study is to investigate the accuracy and safety of intracavitary electrocardiogram (IC-ECG) guidance for the localization of peripherally inserted central catheter (PICC) in neonatal patients. A total of 160 neonatal patients were randomly assigned to receive either anthropometric measurement combined with IC-ECG guidance (n = 80) or conventional anatomical landmark guidance (n = 80) for PICC catheter tip positioning. The catheter tip position was confirmed by postinsertion radiograph and data were interpreted by independent radiologists. Subsequent catheter-related complications of neonates between 2 groups were also compared. The first-attempt target rate was 95.0% (95% confidence interval, 90.1%-99.9%) in IC-ECG-guided PICCs, significantly higher than 78.8% (95% confidence interval, 69.6%-87.9%) in the anatomical landmark guidance group (P < .05). In contrast, IC-ECG-guided PICCs provided a significantly lower overall incidence of the catheter-related complications (3.75%), compared with those guided by anatomical landmarks only (23.75%). Thus, combined use of anatomical landmark and IC-ECG guidance improved the first-attempt target rate of PICC placement and decreased catheter-related complications. These findings indicated a superior accuracy and safety of IC-ECG guidance to conventional anatomical landmark method in neonatal PICC practice.

[Investigation of Lentiviral Vectors Based Integrin ß8 RNAi System in Neonatal Rats' Brain].

OBJECTIVE: To construct lentiviral vectors expressing pSicoR-ß8 shRNA and evaluate its efficiency of RNA interference in neonatal rats' brain. METHODS: Plasmid vectors pSicoR-ß8 shRNA and pSicoR-control,as well as lentiviral packaging system pDM2G,g/p RRE and pRSV Rev were amplified respectively and plasmid DNA was identified by restriction enzyme digestion. Lentiviral packaging system and expressing vector pSicoR-ß8 shRNA/pSicoR-control were co-transfected into packaging cell line 293T. Lentiviral particles expressing ß8-shRNA or control sequence packaged and secreted by 293T were collected,concentrated by PEG-it,and viral titers were assayed by 50% tissue culture infective dose (TCID50). RNAi for integrin ß8 in neonatal rats' brain was performed by intraventricular injection of lentivirus expressing ß8-shRNA and rats received lentivirus expressing ß8-shRNA were served as control. Green fluorescent protein (GFP) expression after intraventricular injection of GFP-Lentivirus was observed under fluorescence microscope,ß8 mRNA and ß8 protein expression were detected by RT-PCR and Western blot respectively,all of which were performed to evaluate the RNAi efficiency and to choose the optimal time for intervention. RESULTS: Restrictive endonuclease digestion and agarose gel electrophoresis showed plasmids as same as the expected size. Lentiviral titers for LV-control after concentration was 1.0×108 PFU/mL,and for LV-ß8 shRNA 5.0×108 PFU/mL.One day after intraventricular injection of lentiviral vectors containing GFP sequence,lenticivirus genome was integrated into host cells and emitted green fluorescence. A relatively strong green fluorescence could be observed in brain slides 2 d,3 d and 5 d after intraventricular injection. Western blot and RT-PCR demonstrated a maximum inhibition happened 3 d after intraventricular injection of LV-ß8 shRNA,the inhibitory rate for ß8 mRNA and ß8 protein were 56% and 51%,respectively. CONCLUSION: Lentiviral vectors expressing ß8-shRNA are successfully constructed and lentiviral mediated ß8-RNAi is successfully applied for in vivo use.

[Efficiency of electrocardiogram monitor for positioning the catheter tip in peripherally inserted central catheter placement in neonates].

OBJECTIVE: To study the efficiency of electrocardiogram (ECG) monitor for positioning the catheter tip in the placement of peripherally inserted central catheter (PICC) in neonates. METHODS: A total of 160 neonates who were admitted to the neonatal intensive care unit (NICU) from January 2015 to December 2017 and underwent the PICC placement via the veins of upper extremity were enrolled. They were randomly divided into an observation group and a control group, with 80 neonates in each group. The neonates in the control group were given body surface measurement and postoperative X-ray localization, while those in the observation group were given body surface measurement, ECG localization, and postoperative X-ray localization. The two groups were compared in terms of general information, one-time success rate of PICC placement, and time spent on PICC placement. RESULTS: There were no significant differences between the two groups in sex composition, gestational age, age in days at the time of PICC placement, disease type, and site of puncture (P>0.05). Compared with the control group, the observation group had a significantly higher one-time success rate of PICC placement (95% vs 79%; P<0.05) and a significantly shorter time spent on PICC placement (P<0.05). Localization under an ECG monitor during PICC placement had a sensitivity of 97% and a specificity of 100%. CONCLUSIONS: During the PICC placement in neonates, the use of ECG monitor to determine the position of catheter tip can improve the one-time success rate of placement and reduce the time spent on placement.

An in vivo study of hypoxia-inducible factor-1α signaling in ginsenoside Rg1-mediated brain repair after hypoxia/ischemia brain injury.

BACKGROUND: Hypoxia/ischemia (HI) brain injury is a common central nervous system insult in newborns. Studies have demonstrated bioactivity of ginsenoside Rg1 in increasing neural viability and promoting angiogenesis. However, there are few reports on roles of Rg1 in brain repair of neonatal HI, and the mechanisms involved are unclear. METHODS: a neonatal HI model was established by a modified Rice-Vannucci model (RVM) and pups received ginsenoside Rg1 or monosialotetrahexosyl ganglioside (GM1) treatment. Neurological function and pathologic damage of rats were evaluated. Cellular apoptosis was detected with Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Immunohistochemistry for von willebrand factor (vwf) was used to label micro vessels. Expression levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and cleaved caspase 3 (CC3) were detected by western blot. RESULTS: Both Rg1 and GM1 reduced neurological impairment and pathologic damage after HI by enhancing neural survival. Rg1, but not GM1, could also facilitate angiogenesis after HI. These pharmacological effects of Rg1 may be attributed to regulation of expression level of VEGF and CC3 and HIF-1α signaling pathway was involved. CONCLUSION: Rg1 plays a neuroprotective role in brain repair following neonatal HI, and HIF-1α is a potential target for therapeutic intervention in neonates with HI brain injury.

[Clinical features of respiratory distress syndrome in neonates of different gestational ages].

OBJECTIVE: To study clinical features of respiratory distress syndrome (RDS) in neonates of different gestational ages (GA). METHODS: According to GA, 133 neonates with RDS were classified into GA <34 weeks group (n=66), GA 34-36 weeks group (late preterm neonates; n=31), and GA ≥37 weeks group (full-term neonates; n=36). The mothers' medical history during pregnancy and the condition of the neonates at birth were retrospectively analyzed, and the clinical data were compared between groups. RESULTS: Prenatal corticosteroids supplementation in the GA <34 weeks group was more common than that in the GA 34-36 weeks group (P<0.05). Compared with the GA ≥37 weeks group and the GA 34-36 weeks group, the GA <34 weeks group showed a significantly lower rate of primary diseases, a significantly later time of the development of dyspnea (P<0.05), and a higher rate of intraventricular hemorrhage (P<0.05). Serum albumin levels in the GA <34 weeks group were significantly lower than in the GA ≥37 weeks group (P<0.05). The GA ≥37 weeks group and the GA 34-36 weeks group showed a significantly higher reuse rate of pulmonary surfactant (P<0.05). Use of high-frequency oscillatory ventilation was more common in the GA ≥37 weeks group compared with the GA <34 weeks group (P<0.05). CONCLUSIONS: The clinical features of RDS are different across neonates of different GA, suggesting that the pathogenesis of RDS may be different in neonates of different GA.

Peripherally inserted central catheter related pericardial effusion/cardiac tamponade in neonates: Analysis of two cases and literature review.

RATIONALE: Peripherally inserted central catheter (PICC)-related pericardial effusion/cardiac tamponade is a rare but fatal complication which cause a high mortality if not timely diagnosed and treated. However, the atypical manifestations and the rapid deterioration present challenges for neonatologists, and there has been limited investigation reported globally to date. Furthermore, a systematic review and comprehensive summary of clinical management are lacking. The significance of this article lies in emphasizing the importance of maintaining vigilance in high-risk neonates and implementing effective management strategies for PICC-related pericardial effusion/cardiac tamponade, thereby contributing to saving more lives. PATIENT CONCERNS: In the current report, we discuss 2 cases of neonatal pericardial effusion/cardiac tamponade following PICC catheterization. DIAGNOSIS: The first case was diagnosed based on forensic autopsy and the second case was diagnosed by bedside echocardiography. INTERVENTIONS AND OUTCOMES: The first case was treated conservatively and the second case underwent pericardiocentesis, unfortunately both were died. LESSONS: Once sudden hemodynamic or respiratory abnormalities are detected in neonates with PICC placement, particularly in the preterm infants, prompt diagnosis by cardiac ultrasound is required to verify pericardial effusion/cardiac tamponade and immediate pericardiocentesis or pericardiotomy is necessary to improve survival.

Role of mammalian target of rapamycin in hypoxic or ischemic brain injury: potential neuroprotection and limitations.

Hypoxic or ischemic stress causes serious brain injury via various pathologic mechanisms including suppressed protein synthesis, neuronal apoptosis, and the release of neurotoxic substances. Many neuroprotective treatments of hypoxic or ischemic brain injury rely on these pathologic mechanisms. The mammalian target of rapamycin (mTOR), an atypical Ser/Thr protein kinase, could be a novel therapeutic target. mTOR plays a critical role in regulating many activities such as protein synthesis, cell growth, and cell death. Furthermore, mTOR could promote angiogenesis, neuronal regeneration, and synaptic plasticity, reduce neuronal apoptosis, and remove neurotoxic substances, which are all closely associated with the repair and survival mechanisms of hypoxic or ischemic brain injury. Although there is currently controversy with regard to regulating the activation of mTOR, the effective neuroprotective functions resulting from mTOR activation have been confirmed by various studies. Considering the potential capability for mTOR in regulating the repair and survival mechanisms of hypoxic or ischemic brain injury, mTOR may be a novel target for neuroprotective treatment.

How to survive a periviable birth baby with birth weight of 450g: A case report.

RATIONALE: An increasing number of periviable birth newborns (PVBs) have emerged with concurrent growing high-risk pregnancy. To date, postnatal management of PVBs remains one of the most challenging issues and limited studies have been reported. PATIENT CONCERNS: A female baby born at 230/7 weeks of gestation with birth weight of 450g. DIAGNOSIS: PVB baby, respiratory distress syndrome (RDS), ventilator associated pneumonia (VAP), intraventricular hemorrhage (IVH), metabolic bone disease of prematurity (MBDP), transient hypothyroxinemia of prematurity (THOP), bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP). INTERVENTIONS: Individualized treatment and intensive care, including neonatal resuscitation, effective respiratory and circulatory support, venous access and nutrition, prevention and treatment of infection, management of endocrine and metabolic problems, individualized nursing such as developmental supportive care, integrated oral motor interventions, skin care, family-integrated-care, etc were performed according to existing literature. OUTCOMES: The baby was discharged home after 138 days of hospitalization with body weight of 2700 g, a full oral feed achieved, and without any requirement of respiratory support or oxygen supply. Now she is 38-month-old, with no significant long-term adverse sequelae. LESSONS: Our case expands the experience and knowledges of individualized and intensive management of PVB babies in their early life days, which increase PVBs' survival and improves their prognosis.

Telomerase reverse transcriptase upregulation attenuates astrocyte proliferation and promotes neuronal survival in the hypoxic-ischemic rat brain.

BACKGROUND AND PURPOSE: Telomerase reverse transcriptase (TERT) is tightly related to the resistance of cells to stress and injury. However, little is known about the roles of TERT in the nervous system. We try to investigate the effects of TERT on the function of astrocytes in developing rat brains subjected to hypoxia-ischemia. METHODS: TERT expression was detected in rat brains with hypoxia-ischemia. In in vitro study, the function of astrocytes with TERT overexpression was measured, and the effects of astrocyte on neuronal apoptosis were examined. Moreover, overexpression or inhibition of TERT was conducted in vivo by gene transduction. Astrocyte proliferation was examined through Ki67 staining. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining and brain infarct volume calculation were used to detect neuronal injury. RESULTS: Both TERT mRNA and protein were upregulated in neurons within 2 days but shifted to astrocytes at Day 3 after hypoxia-ischemia. Astrocyte proliferation was inhibited with TERT overexpression due to the upregulation of cell-cycle regulatory protein p15. Meanwhile, the apoptosis of neurons increased, whereas neurons were cocultured with conditioned media from astrocytes with TERT inhibition compared with TERT overexpression due to the decrease of neurotrophin-3 expression in astrocytes. Furthermore, Ki67-positive astrocytes and neuronal injury were found to be inhibited in TERT-overexpressing rat brains with hypoxia-ischemia. CONCLUSIONS: TERT attenuates astrocyte proliferation and promotes neuronal survival in the developing rat brain after hypoxia-ischemia, partly through its enhancement of p15 and neurotrophin-3 expression in astrocytes.

[Effects of dimethyloxalyl glycine on hypoxic-ischemic brain damage in newborn rats].

OBJECTIVE: To investigate the effects of dimethyloxalyl glycine on hypoxic-ischemic brain damage in newborn rats. METHODS: Forty eight postnatal day 10 SD rats were divided into 3 groups, including sham surgery group, hypoxic-ischemic group and DMOG treated group. The brain tissues were collected at 4, 8, 24 and 72 hours after the hypoxic-ischemic treatment. The expressions of hypoxia inducible factor-1alpha (HIF-1alfa) protein and anti apoptoticprotein cleaved caspase 3 (CC3) were detected by immunohistochemistry. The apoptotic cells were detected by TUNEL staining. RESULTS: The expression level of HIF-1alpha was significantly higher in DMOG treated group than in hypoxic-ischemic group. While the expression level of CC3 was lower and the number of tunel positive cells was fewer in DMOG treated group than that in hypoxic-ischemic group. CONCLUSION: Dimethyloxalyl glycine may play a neuro-protective role in hypoxic-ischemic brain damage in newborn rats by stabilizing HIF-1alpha.

[Risk factors for patent ductus arteriosus in neonates].

OBJECTIVE: To identify the risk factors for patent ductus arteriosus (PDA) in neonates. METHODS: Fifty infants with PDA and 100 infants without PDA were enrolled. Chi-square test, Student's t test and the linear correlation analysis were used to study the clinical data. Logistic regression analysis was used to investigate the independent risk factors for PDA. RESULTS: The prevalence of PDA was negatively correlated with the gestation age (r=-0.03, P<0.05) and birth weight (r=-0.04, P<0.05). Oxygen inhalation was a protective factor for the development of PDA. Fetal distress, meconium-stained amniotic fluid, oligohydramnios, cord entanglement, 1 minute Apgar score <8, maternal infection and hypoxic-ischemic encephalopathy were the independent risk factors for the development of PDA. CONCLUSIONS: The incidence of PDA can be reduced by preventing maternal infection, premature birth, low birth weight and hypoxia.

[Risk factors on the occurrence and prognosis of neonatal hyaline membrane disease].

OBJECTIVE: To identify risk factors with related to the occurrence and prognosis of neonatal hyaline membrane disease (HMD) and to develop effective measures to prevent and treat the disease. METHODS: A case control (1 : 4 paired) study was undertaken, with 62 neonates with HMD as a case group paired with 248 sick neonates without HMD and respiratory disorders as a control group. The controls were matched with the cases by admission time (+/- 7 d), birth weight (+/- 200 g) and gestational age (+/- 3 d). All of the patients came from the neonatal intensive care unit (NICU) in the West China Second University Hospital from June 2008 to January 2009. Conditional logistic regression analysis was performed to identify risk factors associated with the development and prognosis of HMD. RESULTS: Fetal distress, placenta previa, preeclampsia, placental abruption, maternal diabetes, and multiple births were identified as risk factors associated with the development of HMD, with an OR 10.459, 9.382, 8.884, 7.817, 7.727, and 7.217, respectively (P < 0.05). The Cochran Armitage trend test showed that the mortality of HMD decreased with the increase of gestational age and birth weight (P < 0.05). The mortality of HMD increased significantly in the patients with complication such as pulmonary hemorrhage, respiratory failure, neonatal asphyxia, and gastrointestinal hemorrhage (P < 0.05). CONCLUSION: Prevention of premature birth and treatment with high risk pregnancy and complications can reduce the mortality of HMD.

COVID-19: Considerations for Children and Families During the Pandemic.

Coronavirus disease 2019 (COVID-19), a fatal virus caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a pandemic across the world. Despite early concerns, children appear to be less susceptible to acquiring SARS-CoV-2 and manifest minor clinical symptoms compared with adults. However, there still exists a risk of physical and psychological health problems in children and their families. In this review, we summarize the existing information about the mechanism of SARS-CoV-2 infection, the epidemiology of COVID-19, and the clinical manifestations, treatments, and further considerations regarding COVID-19 in children.

In vitro effects of hypoxia-inducible factor 1alpha on the biological characteristics of the SiHa uterine cervix cancer cell line.

INTRODUCTION: Hypoxia-inducible factor 1alpha (HIF-1alpha) regulates the transcription of many genes involved in key aspects of cancer biology. The aim of our study was to explore the effects of HIF-1alpha on the biological characteristics of the uterine cervix cancer (UCC) cell line SiHa, such as proliferation, apoptosis, and migration under normoxia and hypoxia. METHODS: Full-length HIF-1alpha (fL HIF-1alpha) and dominant-negative HIF-1alpha (dn HIF-1alpha) were transfected into UCC SiHa cells. The expression of HIF-1alpha and its targets such as vascular endothelial growth factor (VEGF), CXC chemokine receptor 4 (CXCR4), and human growth and transformation-dependent protein (HGTD-P) was detected by immunocytochemistry, Western blot, and semiquantitative reverse transcription-polymerase chain reaction. Cell proliferation, apoptosis, and migration were surveyed by methyl thiazolyl tetrazolium assay, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining, and scratching test. RESULTS: The expression of HIF-1alpha increased in fL HIF-1alpha but not in dn HIF-1alpha SiHa cells. Consistently, the expression of HIF-1alpha target genes such as VEGF, CXCR4, and HGTD-P increased in fL HIF-1alpha-transfected SiHa cells but decreased in dn HIF-1alpha-transfected SiHa cells. The UCC cells transfected with fL HIF-1alpha had increased cellular proliferation and migration. However, the inhibition of HIF-1alpha through dn HIF-1alpha attenuated cell proliferation and migration under both normoxia and hypoxia. CONCLUSIONS: Hypoxia-inducible factor 1alpha affects the proliferation, apoptosis, and migration of UCC SiHa cells in part by regulating the expression of its target genes such as VEGF, HGTD-P, and CXCR4. Targeting HIF-1alpha may be a promising strategy for molecular therapy for UCC.

[Effect of dominant negative HIF-1alpha (dn HIF-1alpha) on biological characteristics of uterine cervix cancer cells].

OBJECTIVE: To explore the effect of dominant negative HIF-1alpha (dn HIF-1alpha) on biological characteristics of uterine cervix cancer cell SiHa and elucidate the related mechanism. METHODS: pcDNA3. 1-dn HIF-1alpha was transfected into SiHa cells. The expression of HIF-1alpha and VEGF protein were detected by immunocytochemical method and Western Blotting. The growth proliferation of cells was surveyed by the MTT assay and cell apoptosis was detected through TUNEL after treated with CoCl2, meanwhile the results were compared with the group transfected with mock plasmid and untransfected group. RESULTS: After successfully transfected with relevant plasmid, there's no obvious difference of expression of HIF-1alpha among dn HIF-1alpha group, pcDNA3. 1 group, and untransfected group, however the expression of VEGF of dn HIF-1alpha group was significantly lower than that of the others (P < 0. 05). The proliferation ability of dn HIF-1alpha group was obviously lower than that of the other two (P < 0.05), whether it was under normoxia or chemical hypoxia induced by CoCl2. The characteristic apoptotic morphology was most significantly apparent in dn HIF-1alpha group among these three (P < 0.05). CONCLUSION: Domain negative HIF-1alpha can inhibit the proliferation of uterine cervix cancer cell and accelerate its apoptosis under hypoxia induced by CoCl2, as well as decrease the expression of VEGF protein. The implications of all this were that the domain negative HIF-1alpha may play an important role in the therapy of uterine cervix cancer.

[ROLE OF EXTRACELLULAR SIGNAL-RELATED PROTEIN KINASE 1/2 PATHWAY IN GINSENOSIDE Rg1 MEDIATED ANTI-APOPTOTIC EFFECT ON NEURON AFTER HYPOXIA ISCHEMIA BRAIN DAMAGE IN NEONATAL RATS].

OBJECTIVE: To investigate the anti-apoptotic effect of ginsenoside Rg1 in neonatal rats with hypoxia ischemia brain damage (HIBD), and to explore the possible signaling pathway involved in anti-apoptosis. METHODS: Forty-eight 10-day-old Sprague Dawley (SD) rats (weighing 17-21 g, male or female) were randomly allocated into 4 groups (12 rats in each group): sham-operation group (sham group), HIBD group (HI group), HIBD+ginsenoside Rg1 group (HI+Rg1 group), and HIBD+ginsenoside Rg1+U0126 group (HI+Rg1+U0126 group). SD rats in HI group, HI+Rg1 group, and HI+Rg1+U0126 group underwent ligation of the right common carotid artery (CCA) and hypoxic ventilation (8%O2+92%N2) for 2.5 hours to prepare the HIBD model, and rats in sham group underwent only separation of the right CCA. SD rats in HI+Rg1+U0126 group received intraventricular injection of 5 µL phosphate buffer saline (PBS) containing U0126 (25 µg/kg) at 1 hour before HIBD, and rats in the other three groups received intraventricular injection of PBS at the same time. The rats in HI+Rg1 group and HI+Rg1+U0126 group received intraperitoneal injection of 0.1 mL normal saline (NS) containing Rg1 (40 mg/kg) at immediate after HIBD, while rats in HI group and sham group received intraperitoneal injection of 0.1 mL NS at immediate after HIBD. At 4 and 24 hours after HIBD, the right hemisphere and hippocampus were collected to detect the protein expression and distribution of extracellular signal-related protein kinase 1/2 (Erk1/2), phospho-Erk1/2 (p-Erk1/2), hypoxia inducible factor 1α (HIF-1α), and cleaved Caspase-3 (CC3) by Western blot and immunohistochemistry staining. TUNEL staining was used to evaluate neural apoptosis in situ. RESULTS: Western blot results showed that there were expressions of Erk1/2, p-ERK1/2, HIF-1α, and CC3 proteins at 4 and 24 hours after HIBD in each group. The expressions of HIF-1α and CC3 protein at 4 and 24 hours, and expression of p-Erk1/2 protein at 4 hours were significantly increased in HI group when compared with sham group (P<0.05). When compared with HI group, the expressions of p-Erk1/2 and HIF-1α protein in HI+Rg1 group were significantly increased (P<0.05), while the expression of CC3 protein was significantly decreased at 4 and 24 hours (P<0.05). When compared with HI+Rg1 group, the expressions of p-Erk1/2 and HIF-1α proteins in HI+Rg1+U0126 group were significantly decreased (P<0.05), while expression of CC3 protein was significantly increased at 4 and 24 hours (P<0.05). There was no significant difference in Erk1/2 protein expression between groups at different time points (P>0.05). Immunohistochemistry staining displayed that HIF-1α and CC3 proteins mainly distributed in the nucleus and cytoplasma, while Erk1/2 and p-Erk1/2 proteins mainly distributed in the cytoplasma. The expression levels of protein by immunohistochemistry results were similar to the results by Western blot. TUNEL staining showed that the apoptotic neurons were characterized by yellow or brown particle in the nucleus. The apoptotic index (AI) of neurons at 4 and 24 hours was significantly increased in HI group when compared with sham group (P<0.05), and the AI of neurons was significantly decreased in HI+Rg1 group when compared with HI group and HI+Rg1+U0126 group at 24 hours (P<0.05). CONCLUSIONS: Rg1 could enhance HIBD induced HIF-1α expression and inhibit activation of Caspase-3 by Erk1/2 signaling pathway, and play an anti-apoptotic role in neonatal rats with HIBD.

Biological characteristics of prostate cancer cells are regulated by hypoxia-inducible factor 1α

Hypoxia-inducible factor (HIF)-1α has been reported to be associated with malignancy in a number of types of cancer. However, the role of HIF-1 α in the regulation of prostate cancer (PCa) growth has yet to be elucidated. The present study aimed to investigate the effect of HIF-1α on the biological characteristics of the PCa PC3 cell line. Full-length (fL) HIF-1α and dominant-negative (dn) HIF-1α were transfected into PC3 cells. The expression of HIF-1α and its downstream genes, including vascular endothelial growth factor (VEGF), erythropoietin (EPO) and CXC chemokine receptor 4 (CXCR4), were detected using western blot analysis. Cell proliferation, apoptosis and migration were assessed using MTT, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Boyden chamber assays. The expression of VEGF, EPO and CXCR4 was found to be upregulated in the fL HIF-1α-transfected PC3 cells and downregulated in the dn HIF-1α-transfected PC3 cells. The overexpression of HIF-1α was observed to enhance cell proliferation and migration and decrease docetaxol-induced cell apoptosis. However, dn HIF-1α was found to attenuate cell proliferation and migration, and promote docetaxol-induced cell apoptosis. These findings indicate that HIF-1α regulates the proliferation, apoptosis and migration of PC3 cells, at least in part, by regulating the expression of its target genes, including VEGF, EPO and CXCR4. Thus, the use of HIF-1α inhibitors may be a promising therapy for the treatment of PCa.