Three Novel Heterozygous Mutations of NPHS1 Gene Causing Infants with Congenital Nephrotic Syndrome: Two Chinese (Han) Cases.

BACKGROUND: Congenital nephrotic syndrome (CNS) of the Finnish type (CNF) is an autosomal recessively disorder. NPHS1 gene mutation is the main gene responsible for CNF. This study aimed to explore the clinical manifestations and the characteristics of genetic variation in Chinese patients with CNS. METHODS: A 15-minute-old boy and a 34-day-old girl with CNS were included. NPHS1 gene was detected by next-generation high-throughput sequencing. RESULTS: Patient 1 carried two novel heterozygous mutations of NPHS1 gene, one was c.204delG, p. (Leu69fs) in exon 2 of NPHS1 gene, a heterozygote frameshift mutation; the other was c.3558delT, p. (Gly1187fs) in exon 28, a heterozygote frameshift mutation. Patient 2 carried three heterozygous mutations of NPHS1, among them, c.1561-G>A. p.Asp521Asn in exon 12 is a heterozygous missense mutation. It was identified as possible de novo pathogenicity gene. CONCLUSIONS: Three novel heterozygous mutations of NPHS1 gene were responsible for the patients with CNS and can enlarge the spectrum of NPHS1 gene mutation.

Novel classification and risk model based on ferroptosis-related lncRNAs to predict oncologic outcomes for gastric cancer patients.

Gastric cancer (GC) is a highly heterogeneous malignancy, characterized by high mortality and poor prognosis. Ferroptosis is a newly defined nonapoptotic programmed cell death mechanism that has been implicated in the development of various pathological conditions. We aimed to identify ferroptosis-related long noncoding RNA (lncRNAs) that might be used to predict GC prognosis. The data were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database. Two subtypes, C1 and C2, were identified, which had significant variations in prognosis and immune cell infiltrations. Differentially expressed genes between the subtypes were found to be involved in multiple tumor-associated pathways. Subsequently, a training dataset and a testing dataset were created from the TCGA dataset. A predictive model for GC patients based on six ferroptosis-related lncRNAs (including STX18-AS1, MIR99AHG, LINC01197, LINC00968, LINC00865, and LEF1-AS1) was developed. The model could stratify patients into a high- and low-risk group, showing good predictive performance. The testing dataset, entire TCGA dataset, and GSE62254 cohort both confirmed the predictive value of the model. Compared to the clinical parameters (including gender, age, and grade), the risk model was an independent risk factor for GC patients. Moreover, a nomogram (containing our risk score model and clinical parameters) was constructed, which might provide great potential to improve prediction accuracy. Moreover, the single-sample gene set enrichment analysis revealed that the high-risk group was linked to various signaling pathways involved in the regulation of GC progression. Conclusively, a novel classification and risk model based on ferroptosis-related lncRNAs that can predict oncologic outcomes for GC patients has been developed.

Effect of Hypothermia on Serum Myelin Basic Protein and Tumor Necrosis Factor-α in Neonatal Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: Multiple randomized controlled trials have shown that hypothermia is a safe and effective treatment for neonatal moderate or severe hypoxic-ischemic encephalopathy (HIE). The neuroprotective mechanisms of hypothermia need further study. The aim of this study was to investigate the effect of hypothermia on the serum levels of myelin basic protein (MBP) and tumor necrosis factor-α (TNF-α) as well as neurodevelopmental outcomes in neonatal HIE. STUDY DESIGN: Eighty-five neonates with moderate-to-severe HIE were divided into a hypothermia group (n = 49) and a control group (n = 36). Serum levels of MBP and TNF-α within 6 hours after birth and after 3 days of treatment were determined by enzyme-linked immunosorbent assay, and neurodevelopmental outcome at the age of 12 to 15 months was assessed by using the Gesell development scale. RESULTS: After 3 days of treatment, serum levels of MBP and TNF-α in the control group were not significantly different from levels before treatment (p > 0.05), and serum levels of MBP and TNF-α in the hypothermia group were significantly lower than levels before treatment (p < 0.05). Serum levels of MBP and TNF-α were significantly negatively correlated with developmental quotient (DQ; r = - 0.7945, p = 0.0000; r = - 0.7035, p = 0.0000, respectively). Serum levels of MBP and TNF-α in neurodevelopmentally impaired infants were significantly higher than those in infants with suspected neurodevelopmental impairment and those in neurodevelopmentally normal infants (both p < 0.01). The rate of reduction of neurodevelopmental impairment was higher among infants in the hypothermia group than among those in the control group (χ2 = 16.3900, p < 0.05). CONCLUSION: Hypothermia can reduce serum levels of MBP and TNF-α in neonates with HIE. Inhibiting the release of TNF-α may be one of the mechanisms by which hypothermia protects the myelin sheath. KEY POINTS: · Hypothermia can reduce serum levels of MBP and TNF-α in neonatal HIE.. · Hypothermia improves neurodevelopmental outcomes and reduces the rate of neurodevelopmental impairment.. · Hypothermia is a feasible and effective treatment for neonates with moderate or severe HIE..

Neonate with Congenital Thrombotic Thrombocytopenic Purpura: a Case Report of a de novo Compound Heterozygote Mutation in ADAMTS13 Gene and Review of Literature.

BACKGROUND: Congenital thrombotic thrombocytopenic purpura (TTP) is rare and is prone to misdiagnosis or missed diagnosis in clinical. The relationship between genotype and phenotype needs further study. METHODS: A 15-hour-old Chinese girl develops jaundice. Her platelet counts suddenly decreases with bleeding spots on the left side of chest, upper abdomen, and bilateral groin on the fourth day after birth. The plasma ADAMTS13 activity and inhibitor are detected by residual collagen binding assay. ADAMTS 13 gene is detected by next generation sequencing. RESULTS: The plasma ADAMTS13 activity of the patient is shown to be severely deficient, but without inhibitor. Gene sequencing analysis shows that the patient carries a compound heterozygote mutation of ADAMTS13 gene, one is c.1564T>C, p.(Cys522Arg) on exon 13 of the ADAMTS13 gene, a heterozygote missense mutation. It is identified as a de novo suspected pathological variation. The other is c.330+1G>A on intron 3 of the ADAMTS13 gene, a heterozygote splicing mutation. Her father and elder sister carry c.1564T>C, p.(Cys522Arg) on exon 13 of the ADAMTS13 gene, a heterozygote missense mutations. Her mother carries c.330+1G>A on intron 3 of the ADAMTS13 gene, a heterozygote splicing mutation. CONCLUSIONS: The deficiency of ADAMTS13 caused by one heterozygote missense mutation and the other heterozygote splicing mutation are responsible for the episode of this congenital TTP patient.

A Case Report of Primary Neonatal Hypocholinesterase Caused by Homozygous Frameshift Mutation of the utyrylcholinesterase (BCHE) Gene and Review of Literature.

BACKGROUND: Primary neonatal hypocholinesterase is rare; its genetic pattern and mutation still need to be further studied. METHODS: The patient and his parents are studied using next-generation sequencing technology. RESULTS: A boy one day after birth is admitted to the Neonatal Intensive Care Unit at our hospital after experiencing intermittent vomiting for 12 hours. The patient's serum cholinesterase level (113 - 283 U/L) is lower than normal value (4,000 - 12,600 U/L). Many factors of low serum cholinesterase are excluded. We highly suspect that it may be related to congenital factors. Molecular genetic test results show that the patient carried the BCHE gene (NM_000055.2) and has homozygous frameshift mutations at exon 2 c.401dupA (p.Asn134fs) of chromosome 3q26. It is a pathogenicity mutation. This locus mutation belongs to a novel pathogenic mutation. As a result of this mutation, the 134th amino acid Asn began to frameshift and the translation is terminated early. It can cause the Encoding of protein to truncate and lose its normal function. His parents' serum cholinesterase levels (father: 5,135 U/L; mother: 4,367 U/L) are in the normal value range, but his parents carried a heterozygous BCHE gene. CONCLUSIONS: This study suggests that gene sequence detection should be carried out early in hypocholinesterase of nknown cause in neonates. This study can not only improve understanding of the etiology and pathological mechanism of hypocholinesterase, but also it can enlarge the hypocholinesterase gene mutation spectrum.

Neonatal Crohn's disease with Oral ulcer as the first symptom caused by a compound heterozygote mutation in IL-10RA: a case report.

OBJECTIVE: To investigate the clinical and genetic characteristics of neonatal Crohn's disease (CD), improve recognition of neonatal CD, and reduce the number of patients that are missed or misdiagnosed. METHODS: A 10-day-old Chinese girl with oral ulcers was admitted to the Department of Neonatology. She later developed a rash and perianal disease, but without diarrhea and stool abnormalities. The patient and her parents underwent next-generation sequencing. RESULTS: The results showed that the patient carries a compound heterozygous mutation in the interleukin-10 receptor A (IL-10RA) (NM_001558.3) gene. One heterozygous mutation was c.301 c > T, P. (Arg 101 Trp) in exon 3 of IL-10RA (a missense mutation), and the other was c. 537G > A, P. (Thr 179 =) in exon 4 of IL 10RA (a synonymous mutation). The patient's father also carries the c.301 c > T, P. (Arg 101 Trp) heterozygous mutation in exon 3 of IL-10RA, whereas her mother carries the c.537G > A, P. (Thr 179 =) heterozygous mutation in exon 4 of IL-10RA. CONCLUSIONS: The results show that a compound heterozygous mutation in IL-10RA is associated with neonatal CD. Oral ulcers with a rash and perianal disease may be an early symptom of neonatal CD; therefore, such patients should undergo genetic identification as soon as possible.

SATB2-Associated Syndrome: a Case Report of a De Novo Nonsense Mutation in SATB2 from China and Review of Literature.

BACKGROUND: To study the clinical and genetic features from a Chinese child with SATB2-associated syndrome (SAS) and review of literature. METHODS: The girl, 2 years 3 months old, is admitted to the Department of Pediatric Rehabilitation in our hospital. This patient has mental retardation, language development disorder, cleft palate II0, micrognathia, malocclusion, irritability and bilateral oblique palpebral fissure as a clinical manifestation and is treated for 3 months. RESULTS: Gesell Development Scale (GDS) evaluation displays the patient's action capacity: gross motor 13.4, DQ 41%; fine motor 14.1, DQ 44%; adaptive behavior: DA 15.2, DQ 47%; speech capacity: DA 8.8; DQ 27%; person capacity: DA 11.7, DQ, 36%. Bayley Scale evaluation displays MDI < 50 and PDI < 50. Sleep EEG showed bilateral frontal pole - frontal - central - anterior temporal area presents in sharp wave, sharp and slow wave synchronization issue. A brain MRI showed that signal T2 is strengthened in the internal capsule hind leg. Flake T2FLATR high signal can been showed in the periventricular area of the parietal lobe in bilateral hemisphere. Molecular studies showed the patient carries a de novo nonsense mutation c.1285G>A (p.R429X) in SATB2. CONCLUSIONS: SATB2 mutation is not detected in the parents of the subjects. This study is important to further study the clinical features of SATB2-associated syndrome and to enlarge the SATB2 mutation spectrum.

Predictive Value of Neurodevelopmental Outcome and Serum Tau Protein Level in Neonates with Hypoxic Ischemic Encephalopathy.

BACKGROUND: Tau protein is s specific protein expressed by neurons in the central nervous system. Elevated serum Tau protein is associated with many diseases of the central nervous system. The serum Tau protein level in neonates with hypoxic ischemic encephalopathy (HIE) is still poorly understood. METHODS: Forty-one human neonates with HIE and thirty-five healthy neonates (control group) within 24 hours after birth were studied. Tau protein in serum was detected by enzyme-linked immunosorbent assay. Neurological outcome was assessed at 9 months of age according to the Gesell developmental scale. RESULTS: Tau protein in serum was significantly higher in the HIE group than in the control group (p < 0.01), in neonates with severe HIE than neonates with moderate HIE (p < 0.01), and in infants with neurodevelopmental retardation compared with those with normal neurodevelopment (p < 0.01). The result of this study showed an obvious negative correlation between the serum Tau protein level and development quotients of neonates with HIE (rs = -0.6172, p < 0.01). Receiver operator characteristic curve analysis showed that Tau protein (cutoff value 933.04 pg/mL) was a predictor of neurodevelopmental retardation outcome (AUC value = 0.860 (95% CI: 0.736 - 0.983, p < 0.01), sensitivity 100%, specificity 70.8%). CONCLUSIONS: Serum Tau protein level within 24 hours after birth can be used as a marker for the early diagnosis of neonatal HIE and predicting neurodevelopmental outcomes.

Neuronavigation-assisted trajectory planning for deep brain biopsy with susceptibility-weighted imaging.

BACKGROUND: Susceptibility-weighted imaging (SWI) exploits susceptibility differences between tissues to enhance contrast in magnetic resonance imaging to enable the visualization of small blood vessels that are difficult to detect by other contrast agents. This study explored the value of SWI-based planning for neuronavigation-guided deep brain biopsies to reduce the incidence of post-surgical complications. METHODS: The cohort of 84 patients was divided into 41 biopsies performed aided by SWI (SWI group) and 43 biopsies based on conventional T1w-Gd-based imaging (T1w-Gd group). Biopsy targets were determined using magnetic resonance spectroscopy (MRS) before the operation, and the safest trajectory was selected based on preoperative images of blood vessels. RESULTS: Within 24 h of surgery, there was no radiographically identified bleeding, no blood extravasation and no clinical intracranial hypertension in the SWI group. Only one patient (2.5 %) with basal ganglia lymphoma developed transient hemiparesis after biopsy, who later recovered after undergoing symptomatic treatment. Complication rates in the SWI group were lower than in the T1w-Gd group, where a 7 % morbidity rate was encountered with one patient developing a permanent neurological deficit and two showing biopsy-associated hemorrhages. SWI imaging yielded a better visualization of subcortical vessels and deep-seated brain structures. CONCLUSIONS: SWI-based imaging revealed significantly better visualization of small-caliber vasculature that was not detectable on conventional T1w-Gd imaging, minimizing damage to the brain and reducing postoperative complications. Furthermore, MRS can contribute significantly to target selection to improve the yield of image-guided biopsies.

[The Role of Notch Signaling Pathway in Adult Patients with Epstein-Barr Virus-induced Infectious Mononucleosis].

OBJECTIVE: To investigate the changes of Notch signaling molecules and Th22 cells in adult patients with infectious mononucleosis (IM), and assess the regulatory function of Notch signaling inhibition to Th22 cells. METHODS: Forty-two IM patients and twenty-one healthy controls were enrolled in this study. Their peripheral blood was collected, from which plasma and peripheral blood mononuclear cells (PBMCs) were isolated. Plasma interleukin (IL)-17 and IL-22 were measured by enzyme-linked immunosorbent assay. The percentages of CD3+ CD4+ IL-17+ Th17 cells and CD3+ CD4+ IL-22+ Th22 cells were investigated by flow cytometry. The mRNA relative levels corresponding to Th17 transcription factor retinoic acid related orphan receptor γt (RORγt), Th22 transcription factor aryl hydrocarbon receptor (AhR), and Notch signaling pathway molecules (including Notch receptors, Notch ligands, Notch downstream molecules) were semi-quantified by real-time PCR. CD4+ T cells were purified and stimulated with γ-secretase inhibitor (GSI). Cellular proliferation, Th17 and Th22 percentage, IL-17 and IL-22 secretion, transcription factor mRNA were measured in response to GSI stimulation. RESULTS: The relative expression levels of Notch1 and Notch2 mRNA in PBMCs of IM group were 13.58±3.18 and 4.73±1.16, respectively, which were significantly higher than 1.09±0.12 and 1.07±0.15 in PBMCs of control group (both P < 0.001). However, there were no significant differences in relative expression levels of Notch3 and Notch4 mRNA between IM group and control group (P >0.05). The relative expression levels of Notch ligands (including DLL1 and Jagged1 ) mRNA and Notch downstream molecules (including Hes1, Hes5, and Hey1 ) were increased in IM group compared with control group (all P < 0.001). In IM group, the Th17 and Th22 percentage were 5.03%±1.15% and 4.48%±1.29%, respectively, which were both higher than 4.36%±0.82% and 3.83%±0.55% in control group (both P < 0.05). In IM group, the IL-17 and IL-22 level were (301.1±53.82) and (101.2±16.45) pg/ml, respectively, which were both higher than (237.2±72.18) and (84.75±11.83) pg/ml in control group (both P < 0.001). In IM group, the relative expression levels of RORγt and AhR mRNA were 1.25±0.22 and 1.21±0.12, respectively, which were both higher than 0.99±0.15 and 1.04±0.11 in control group (both P < 0.001). There were no remarkable differences in CD4+ T cell proliferation, Th17 percentage, IL-17 secretion, and relative expression level of RORγt mRNA between cells with GSI stimulation and without GSI stimulation (P >0.05). GSI stimulation reduced Th22 percentage, IL-22 secretion, and relative expression level of AhR mRNA compared with non-stimulation (all P < 0.05). CONCLUSION: Notch signaling pathway regulates IL-22 secretion by CD4+ T cells via AhR in IM patients. Notch-AhR-Th22 pathway may take part in the pathogenesis of IM.

A biochemical feedback signal for hypothermia treatment for neonatal hypoxic-ischemic encephalopathy: focusing on central nervous system proteins in biofluids.

Hypothermia has been widely used to treat moderate to severe neonatal hypoxic-ischemic encephalopathy (HIE), yet evaluating the effects of hypothermia relies on clinical neurology, neuroimaging, amplitude-integrated electroencephalography, and follow-up data on patient outcomes. Biomarkers of brain injury have been considered for estimating the effects of hypothermia. Proteins specific to the central nervous system (CNS) are components of nervous tissue, and once the CNS is damaged, these proteins are released into biofluids (cerebrospinal fluid, blood, urine, tears, saliva), and they can be used as markers of brain damage. Clinical reports have shown that CNS-specific marker proteins (CNSPs) were early expressed in biofluids after brain damage and formed unique biochemical profiles. As a result, these markers may serve as an indicator for screening brain injury in infants, monitoring disease progression, identifying damage region of brain, and assessing the efficacy of neuroprotective measures. In clinical work, we have found that there are few reports on using CNSPs as biological signals in hypothermia for neonatal HIE. The aim of this article is to review the classification, origin, biochemical composition, and physiological function of CNSPs with changes in their expression levels after hypothermia for neonatal HIE. Hopefully, this review will improve the awareness of CNSPs among pediatricians, and encourage future studies exploring the mechanisms behind the effects of hypothermia on these CNSPs, in order to reduce the adverse outcome of neonatal HIE.

A clinical warning in the treatment of chlorfenapyr poisoning.

Chlorfenapyr, an arylpyrrole-based insecticide, disrupts mitochondrial oxidative phosphorylation to deprive the target organism of energy. Chlorfenapyr poisoning in humans causes distinct clinical signs such as hyperhidrosis, malignant hyperthermia, rhabdomyolysis, and delayed neurological symptoms that worsen over time and can be fatal. When treating acute chlorfenapyr poisoning, physicians must consider the latent period and not assume that a patient is safe after an initial response to treatment. It is important to take measures before sudden, fatal symptoms appear. This paper presents three cases of chlorfenapyr poisoning as a warning for physicians to understand its clinical course and treatment.

Study on serum Tau protein level and neurodevelopmental outcome of placental abruption with neonatal hypoxic-ischemic encephalopathy.

Objective: The aim of this study was to explore differences in serum Tau protein levels and neurodevelopmental prognoses of placental abruption or umbilical cord around neck with hypoxic-ischemic encephalopathy (HIE).Methods: Forty neonates with moderate/severe HIE divided into placental abruption with HIE group (placental abruption with hypoxic-ischemic encephalopathy (PA-HIE) group) (n = 18) and umbilical cord around the neck with HIE group (umbilical cord around the neck with hypoxic-ischemic encephalopathy (UCAN-HIE) group) (n = 22). Healthy term newborns comprised the control group (n = 35). Serum Tau protein levels were measured using an enzyme-linked immunosorbent assay 24 hours (3.50 hours [1.00-24.00]) after birth. Neurodevelopment outcomes were assessed based on the Gesell Developmental Scale at 9 months of age.Results: Serum Tau protein levels were significantly higher in 40 cases (1013 pg/ml [538.04-1190.42]) than in the control group (106.41 pg/ml [64.55-154.71], p = .0001). Serum Tau protein levels in the PA-HIE group (1024.46 pg/ml [657.88-1190.42]) were significantly higher than those in the UCAN-HIE group (892.78 pg/ml [538.04-1179.50], p = .0149). The development quotient score in the PA-HIE group (67.0 [47.0-90.0]) was significantly lower than that in the UCAN-HIE group (81.5 [52.6-100.0]) (p = .0028). The component ratio of neurodevelopmental retardation in the PA-HIE group (44.45%) was significantly higher than that in the UCAN-HIE group (22.73%) (X2 = 13.3138, p = .0013).Conclusions: Compared with the UCAN-HIE group, the serum Tau protein level and the component ratio of neurodevelopmental retardation were significantly higher in the PA-HIE group.

Neonatal hypoxic-ischemic encephalopathy: emerging therapeutic strategies based on pathophysiologic phases of the injury.

Neonatal hypoxic ischemic encephalopathy (HIE) is an important cause of neonatal death and disability. At present, there is no unified standard and specialized treatment method for neonatal HIE. In clinical practice, we have found that a gap remains between preclinical medical research and clinical application in the treatment of neonatal HIE. To promote an organic combination of preclinical research and clinical application, we propose the different phases as intervention targets, based on the pathophysiologic changes in phases I, II, and III of neonatal HIE; moreover, we suggest transformative medicine as a principle that may improve the therapeutic effect by blocking the progression of the disease to an irreversible stage. For instance, in phase I, mild hypothermia, free radical scavenger (erythropoietin, hydrogen-rich saline), excitatory amino acid receptor blocker, and neuroprotective agents should be administered to neonates with moderate/severe HIE; in phase II, following phase I treatment, anti-inflammatory agents, neuroprotective or nerve regeneration agents, and stem cell transplantation should be administered to patients; in phase III, anti-inflammatory agents, neuroprotective or nerve regeneration agents, and stem cell transplantation should be administered to patients. As soon as the patient's condition has stabilized, acupuncture, massage, and rehabilitation training should be performed. Following further study of stem cells, stem cell transplantation is expected to become the most promising therapeutic candidate for treatment of severe neonatal HIE with its sequelae.

Rare double heterozygosity for poly A(A〉 G) and CD17(A〉 T) of beta thalassemia intermedia in a Chinese family.

Beta thalassemia is a hereditary disorder resulted from mutations in the ß globin gene leading to alpha/beta imbalance, ineffective erythropoiesis, and chronic anemia. Three types have been defined, based on the degree of reduced beta-globin chain synthesis and clinical phenotype: major, intermedia and minor (heterozygote carrier state). Beta thalassemia intermedia is characterized by heterogeneity for the wide clinical spectrum of various genotypes and a wide range of presentations. The genotypes of beta thalassemia intermedia are much complicated referring to ß+/ß+,ß+/ß0, Hb E/ß0, ß0/ß0 compounding alpha thalassemia and so on. In this present case, we reported a rare beta thalassemia intermedia genotype of double heterozygosity for poly A (A〉 G) and CD17(A〉 T) indicated of ß+/ß0 in a Chinese family.

Effect of erythropoietin combined with hypothermia on serum tau protein levels and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy.

Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic encephalopathy, many neonatal patients die or suffer from severe neurological dysfunction. Erythropoietin is considered one of the most promising neuroprotective agents. We hypothesized that erythropoietin combined with hypothermia will improve efficacy of neonatal hypoxic-ischemic encephalopathy treatment. In this study, 41 neonates with moderate/severe hypoxic-ischemic encephalopathy were randomly divided into a control group (hypothermia alone for 72 hours, n = 20) and erythropoietin group (hypothermia + erythropoietin 200 IU/kg for 10 days, n = 21). Our results show that compared with the control group, serum tau protein levels were lower and neonatal behavioral neurological assessment scores higher in the erythropoietin group at 8 and 12 days. However, neurodevelopmental outcome was similar between the two groups at 9 months of age. These findings suggest that erythropoietin combined with hypothermia reduces serum tau protein levels and improves neonatal behavioral neurology outcome but does not affect long-term neurodevelopmental outcome.

[Analysis of the mode of inheritance in familial bronchial asthma].

To study the mode of inheritance of familial bronchial asthma and to understand the population genetics laws of bronchial asthma, Families with a family history of bronchial asthma in Handan region were investigated using group research method. The xi2 test of the degree of coincidence between the expected and observed values was analyzed by pedigree analysis and the "Smith" agonic revise method. The incidence rate within the 72 families pedigree with familial bronchial asthma, including 109 core pedigrees, is 0.46. Analysis shows a tendency towards single gene inheritance. Pedigree analysis reveals that it is consistent with autosome dominant inheritance. Analysis of the D- x dd marriage with the "Smith" analytical method supports this conclusion (xi2 = 3.181, P > 0.05) and further hints there exists genetic heterogeneity, i.e. different modes of inheritance among different marriage types. Our results can offer the reference to the prevention, diagnosis and treatment of familial bronchial asthma.

Neonatal hypoxic ischemic encephalopathy-related biomarkers in serum and cerebrospinal fluid.

Neonatal hypoxic ischemic encephalopathy (HIE) is a common disease caused by perinatal asphyxia, a major cause of neonatal death, neurological behavior, and long-term disability. Currently, the diagnosis and prognosis of neonatal HIE are based on nervous system clinical manifestations, imaging and electrophysiological examination. These take time and late diagnosis allows brain injury to occur in newborns, so that infants of many brain injury missed the best treatment time, left with varying degrees of neurological sequelae. The use of biomarkers to monitor brain injury and evaluate neuroprotective effects might allow the early intervention and treatment of neonatal HIE to reduce mortality rates. This study reviewed the mechanism of neonatal hypoxic ischemic encephalopathy in relation to numerous brain-related biomarkers including NSE, S-100ß, GFAP, UCH-L1, Tau protein, miRNA, LDH, and CK-BB. In early diagnosis of neonatal HIE, S-100ß and activin A seems to be better biomarkers. Biomarkers with the greatest potential to predict long-term neurologic handicap of neonates with HIE are GFAP and UCH-L1 and when combined with other markers or brain imaging can increase the detection rate of HIE. Tau protein is a unique biological component of nervous tissues, and might have value for neonatal HIE diagnosis. Combination of more than two biological markers should be a future research direction.

Immunoexpression and prognostic role of p53 in different subtypes of epithelial ovarian carcinoma.

We sought to investigate the significance of p53 expression for epithelial ovarian carcinoma. In this study, we used immunohistochemical method to investigate the expression patterns of p53 in different subtypes of epithelial ovarian carcinoma. We found that the expressions of p53 protein in epithelial ovarian cancer (pituita, serosity and intima) were 88.9%, 75% and 100%, respectively, while the recurrence rates among three cancer subtypes were significantly different (33.3%, 12.5% and 0%, respectively; P < 0.05). Compared with patients without lymph node metastasis, the expression of p53 in patients with lymph node metastasis was significantly strong (68.75% and 100%, respectively; P < 0.05). However, the recurrence rate in the patients with lymph node metastasis (40%) was higher than that without lymph node metastasis (6.25%, P < 0.05). The expressions of p53 protein in ovarian cancer between I-II (25%) stage and II-IV stage (100%) were significantly different (P < 0.05), and the recurrence rates between the two groups were significantly different (0% and 31.25%, respectively, P < 0.05). Therefore, p53 protein has an intimate relationship with the malignant degree and the prognosis of ovarian cancer.

Autophagy induced by baicalin involves downregulation of CD147 in SMMC-7721 cells in vitro.

Baicalin has been demonstrated to exert anticancer effects mainly through induction of tumor cell apoptosis and cell cycle arrest. However, the precise mechanisms underlying its anticancer role remain to be elucidated. In the present study, we investigated whether autophagy was involved in the anticancer activity of baicalin in the human hepatocellular carcinoma (HCC) cell line SMMC-7721 and the possible molecular mechanisms. Our data showed that the viability of SMMC-7721 cells was significantly inhibited by baicalin in a dose- and time-dependent manner. Alongside apoptosis, autophagy was also induced by baicalin dose- and time-dependently with the involvement of the autophagy-associated protein Βeclin 1. Moreover, we demonstrated that cell death induced by baicalin was significantly inhibited by the apoptosis inhibitor z-DEVD-fmk or the autophagy inhibitor 3-MA, respectively. In addition, we found that CD147, a key molecule related both to apoptosis and autophagy, was markedly downregulated at the protein level in SMMC-7721 cells treated with baicalin. Collectively, this is the first study to suggest that baicalin induces autophagic cell death in SMMC-7721 cells, which involves the downregulation of CD147. Our study reveals a new mechanism for the anticancer effects of baicalin and puts forward a potential crucial role of CD147 in baicalin-induced cancer cell death.