[Risk factors for neonatal asphyxia and establishment of a nomogram model for predicting neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture: a multicenter study]. / æ¹–åŒ—æ©æ–½åœŸå®¶æ—è‹—æ—è‡ªæ²»å·žæ–°ç”Ÿå„¿çª’æ¯å±é™©å› ç´ åˆ†æžåŠåˆ—çº¿å›¾é¢„æµ‹æ¨¡åž‹çš„æž„å»ºï¼šä¸€é¡¹å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS: The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.

Adult-Onset Neuronal Ceroid Lipofuscinosis With a Novel DNAJC5 Mutation Exhibits Aberrant Protein Palmitoylation.

Neuronal ceroid lipofuscinosis (NCL) is composed of a group of inherited neurodegenerative diseases, with the hallmark of lipofuscin deposit (a mixture of lipids and proteins with metal materials) inside the lysosomal lumen, which typically emits auto-fluorescence. Adult-onset NCL (ANCL) has been reported to be associated with a mutation in the DNAJC5 gene, including L115R, L116Δ, and the recently identified C124_C133dup mutation. In this study, we reported a novel C128Y mutation in a young Chinese female with ANCL, and this novel mutation caused abnormal palmitoylation and triggered lipofuscin deposits.

microRNA-425 loss mediates amyloid plaque microenvironment heterogeneity and promotes neurodegenerative pathologies.

Different cellular and molecular changes underlie the pathogenesis of Alzheimer's disease (AD). Among these, neuron-specific dysregulation is a necessary event for accumulation of classic pathologies including amyloid plaques. Here, we show that AD-associated pathophysiology including neuronal cell death, inflammatory signaling, and endolysosomal dysfunction is spatially colocalized to amyloid plaques in regions with abnormal microRNA-425 (miR-425) levels and this change leads to focal brain microenvironment heterogeneity, that is, an amyloid plaque-associated microenvironment (APAM). APAM consists of multiple specific neurodegenerative signature pathologies associated with senile plaques that contribute to the heterogeneity and complexity of AD. Remarkably, miR-425, a neuronal-specific regulator decreased in AD brain, maintains a normal spatial transcriptome within brain neurons. We tested the hypothesis that miR-425 loss correlates with enhanced levels of mRNA targets downstream, supporting APAM and AD progression. A miR-425-deficient mouse model has enhanced APP amyloidogenic processing, neuroinflammation, neuron loss, and cognitive impairment. In the APP/PS1 mouse model, intervening with miR-425 supplementation ameliorated APAM changes and memory deficits. This study reveals a novel mechanism of dysregulation of spatial transcriptomic changes in AD brain, identifying a probable neuronal-specific microRNA regulator capable of staving off amyloid pathogenesis. Moreover, our findings provide new insights for developing AD treatment strategies with miRNA oligonucleotide(s).

Successful treatment of hypervirulent Klebsiella pneumoniae bacteremia with combination carbapenem and rifampicin.

Hypervirulent Klebsiella pneumoniae (hvKP) with a high mucus phenotype, can cause liver abscess and extrahepatic invasive infection. The morbidity of hvKP infections has increased recently. Here we describe a case report of septicemia caused by hvKP due to the term septic arthritis of right knee joint in a 29-year-old male. The patient was persistent fever with a peak temperature at 40.6 °C. However, based on the drug sensitivity, the treatment failed frequently. The patient did not improve clinically on susceptible monotherapy antimicrobial. Combination therapy with meropenem and rifampicin (RFP) lead to clinical improvement and discharge.

[A clinical epidemiological investigation of neonatal acute respiratory distress syndrome in southwest Hubei, China].

OBJECTIVE: To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China. METHODS: According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017. RESULTS: A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66). CONCLUSIONS: Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.

[Effect of two manual mixing methods on the accuracy of alginate impression].

PURPOSE: The effect of clockwise mixing method and clockwise combined eight-shaped mixing method on the accuracy of alginate impression was compared. METHODS: From march to April 2018, 40 dental restoration cases in the Department of Stomatology, Zhoupu Hospital, Pudong District, Shanghai were selected. Two nurses and the same doctor treated 40 patients with single crown porcelain restoration. Two sets of models were taken by two kinds of mixing methods, which were divided into experimental group and control group. Clockwise manual mixing method was used in the control group to take the model, while clockwise combined eight-shaped mixing method was used in the experimental group to take the model. SPSS 24.0 software package was used for Mann-Whitney rank sum test. RESULTS: The same high-grade technician used a magnifying glass to observe the prepared impression, recorded the shoulder print, the sulcus wing and bubble generation, and comprehensively evaluated the impression quality. A comparison was made between the two groups, Z=-4.634, P<0.001, and the difference was statistically significant. Among them, the ratio of excellent quality of the clockwise combined eight-shaped mixing method (77.5%) was significantly higher than that of the clockwise mixing method (10%), and the proportion of level IV unqualification (2.5%) was significantly lower than that of the clockwise mixing method (27.5%). CONCLUSIONS: The quality of impression using clockwise combined eight-shaped mixing method is higher than that of the clockwise method, which improves the success rate of the mold and reduces the discomfort caused by repeated impression. Application of this technique is helpful to the promotion of occult knowledge among nurses.

miR-425 deficiency promotes necroptosis and dopaminergic neurodegeneration in Parkinson's disease.

A major hallmark of Parkinson's disease (PD) is the degeneration of dopaminergic neurons in the substantia nigra, and the causative mechanism is thought to be the activation of programmed neuronal death. Necroptosis is a regulated process of cell death triggered by RIPK1. Although the pathophysiology of PD has been studied extensively, the cellular mechanism underlying dopaminergic neuron death remains unclear. In this study, we detected a specific miRNA, miR-425, in response to MPTP toxicity and dopaminergic degeneration. In MPTP-treated mice, we observed necroptosis activation and miR-425 deficiency in the substantia nigra, which is correlated with dopaminergic neuron loss. This miRNA targeted RIPK1 transcripts and promoted the phosphorylation of MLKL and necroptosis. Similarly, in the brains of PD patients, miR-425 deficiency and necroptosis activation were also confirmed in dopaminergic neuron. Furthermore, we found that genetic knockdown of miR-425 aggravated MPTP-induced motor deficits and dopaminergic neurodegeneration via early upregulation of necroptotic genes. Intracerebral miR-425 mimics (AgomiR-425) treatment attenuated necroptosis activation and dopaminergic neuron loss, and improved locomotor behaviors. In conclusion, our study suggests that miR-425 deficiency triggers necroptosis of dopaminergic neurons, and targeting miR-425 in MPTP-treated mice restored dysfunctional dopaminergic neurodegeneration and ameliorated behavioral deficits. These findings identify brain delivery of miR-425 as a potential therapeutic approach for the treatment of PD.

Rho-associated coiled-coil kinase 1 activation mediates amyloid precursor protein site-specific Ser655 phosphorylation and triggers amyloid pathology.

Rho-associated coiled-coil kinase 1 (ROCK1) is proposed to be implicated in Aß suppression; however, the role for ROCK1 in amyloidogenic metabolism of amyloid precursor protein (APP) to produce Aß was unknown. In the present study, we showed that ROCK1 kinase activity and its APP binding were enhanced in AD brain, resulting in increased ß-secretase cleavage of APP. Furthermore, we firstly confirmed that APP served as a substrate for ROCK1 and its major phosphorylation site was located at Ser655. The increased level of APP Ser655 phosphorylation was observed in the brain of APP/PS1 mice and AD patients compared to controls. Moreover, blockade of APP Ser655 phosphorylation, or inhibition of ROCK1 activity with either shRNA knockdown or Y-27632, ameliorated amyloid pathology and improved learning and memory in APP/PS1 mice. These findings suggest that activated ROCK1 targets APP Ser655 phosphorylation, which promotes amyloid processing and pathology. Inhibition of ROCK1 could be a potential therapeutic approach for AD.

The association between body lead levels and childhood rickets: A meta-analysis based on Chinese cohort.

China has serious lead pollution and a high incidence of childhood rickets. High lead levels have been reported in childhood rickets, but the results were inconsistent.To evaluate the association between body lead levels and childhood rickets.After a systematic literature search, we identified 15 studies determining body lead levels between rickets children and healthy controls, and 4 studies focusing on the cases of different disease severity. Standard mean differences (SMD) and the corresponding 95% confidence intervals (CI) were pooled to compare the lead levels between different groups.Sixteen case-control studies were included with a total of 5082 cases and 6054 controls. Compared with healthy controls, the body lead levels in rickets children were significantly higher (SMD (95%CI): 0.67 (0.41-0.93)), and subgroup analyses showed consistent results. The cases with moderate-to-severe disease activity also had a significantly higher lead level than mild-to-moderate cases (SMD (95%CI): 0.64 (0.31-0.97)).This meta-analysis suggested an association between body lead levels and childhood rickets, and lead exposure might be a risk factor for rickets.

Echogenic alteration in the raphe nuclei measured by transcranial sonography in patients with Parkinson disease and depression.

BACKGROUND: Recently, several studies using transcranial sonography (TCS) have demonstrated reduced echogenicity of the mesencephalic midline in unipolar depression and patients with comorbid depression and Parkinson disease (PD). However, there is no consensus on the conclusion that raphe nuclei (RN) hypoechogenicity is associated with depression in PD. The methods used in previous studies lack quantitative and objective indicators to some extent; therefore, the present study used the level of platelet 5-hydroxytryptamine (5-HT) as an objective indicator of depression. Additionally, the reason for the reduced echogenicity of the brainstem raphe is still unclear. OBJECTIVES: The purpose of the present study was to assess the correlation between alterations in RN echogenicity and depressive symptoms in patients with PD using transcranial sonography (TCS). This information could provide a meaningful clinical reference for the antidiastole between depressive symptoms in PD and unipolar depression in patients with PD in whom depressive symptoms occur before motor symptoms. METHODS: TCS was performed in patients with PD, patients with PD and depression, patients with depression and no PD, and healthy controls. Using the red nucleus as a reference, the RN was rated from grades 0 to 1 (grade 0: invisible, slightly echogenic, or interrupted RN; grade 1: hyperechogenicity in the RN observed as a continuous line). RESULTS: The rate of abnormal RN (grade 0) was found to be 16.67% in patients with PD (5/30) and 14.29% in healthy controls (4/28). The presence of abnormal RN was significantly higher (χ = 15.983, P < .05) in patients with depression and PD (40%, 12/30) and in patients with depression only (58.33%, 14/24) than in those without depression and healthy controls. No correlation was found between RN changes and depression severity (P > .05). There were no statistical differences in the concentration of platelet serotonin among the 4 groups (P > .05). CONCLUSIONS: TCS of the mesencephalic midline may be useful for detecting depression, which is an early symptom of PD. However, further neuropathological studies are needed to understand the principles underlying the use of platelet serotonin as a peripheral biomarker, as well as the connection between PD and depression.

Comment on: Macronutrient Intake and Risk of Crohn's Disease: Systematic Review and Dose-Response: Meta-Analysis of Epidemiological Studies, Nutrients 2017, 9, 500.

We read with great interest the article by Zeng et al. recently published in Nutrients [1].[...].

The development prospection of HDAC inhibitors as a potential therapeutic direction in Alzheimer's disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is associated with learning and memory impairment in the elderly. Recent studies have found that treating AD in the way of chromatin remodeling via histone acetylation is a promising therapeutic regimen. In a number of recent studies, inhibitors of histone deacetylase (HDACs) have been found to be a novel promising therapeutic agents for neurological disorders, particularly for AD and other neurodegenerative diseases. Although HDAC inhibitors have the ability to ameliorate cognitive impairment, successful treatments in the classic AD animal model are rarely translated into clinical trials. As for the reduction of unwanted side effects, the development of HDAC inhibitors with increased isoform selectivity or seeking other directions is a key issue that needs to be addressed. The review focused on literatures on epigenetic mechanisms in recent years, especially on histone acetylation in terms of the enhancement of specificity, efficacy and avoiding side effects for treating AD.

Numerical study on the lubrication performance of compression ring-cylinder liner system with spherical dimples.

The effects of surface texture on the lubrication performance of a compression ring-cylinder liner system are studied in this paper. By considering the surface roughness of the compression ring and cylinder liner, a mixed lubrication model is presented to investigate the tribological behaviors of a barrel-shaped compression ring-cylinder liner system with spherical dimples on the liner. In order to determine the rupture and reformulation positions of fluid film accurately, the Jacoboson-Floberg-Olsson (JFO) cavitation boundary condition is applied to the mixed lubrication model for ensuring the mass-conservative law. On this basis, the minimum oil film thickness and average friction forces in the compression ring-cylinder liner system are investigated under the engine-like conditions by changing the dimple area density, radius, and depth. The wear load, average friction forces, and power loss of the compression ring-cylinder liner system with and without dimples are also compared for different compression ring face profiles. The results show that the spherical dimples can produce a larger reduction of friction in mixed lubrication region, and reduce power loss significantly in the middle of the strokes. In addition, higher reduction percentages of average friction forces and wear are obtained for smaller crown height or larger axial width.

ROCK1 Is Associated with Alzheimer's Disease-Specific Plaques, as well as Enhances Autophagosome Formation But not Autophagic Aß Clearance.

Alzheimer's disease (AD) is the most prevalent form of late-life dementia in the population, characterized by amyloid plaque formation and increased tau deposition, which is modulated by Rho-associated coiled-coil kinase 1 (ROCK1). In this study, we further analyze whether ROCK1 regulates the metabolism of amyloid precursor protein (APP). We show that ROCK1 is colocalized with mature amyloid-ß (Aß) plaques in patients with AD, in that ROCK1 enhances the amyloidogenic pathway, and that ROCK1 mediated autophagy enhances the intracellular buildup of Aß in a cell model of AD (confirmed by increased ROCK1 and decreased Beclin 1 protein levels, with neuronal autophagosome accumulation in prefrontal cortex of AD APP/PS1 mouse model). In vitro over-expression of ROCK1 leads to a decrease in Aß secretion and an increase in the expression of autophagy-related molecules. ROCK1 interacts with Beclin1, an autophagy initiator, and enhances the intracellular accumulation of Aß. Reciprocally, overexpression of APP/Aß promotes ROCK1 expression. Our data suggest ROCK1 participates in regulating Aß secretion, APP shedding and autophagosome accumulation, and that ROCK1, rather than other kinases, is more likely to be a targetable enzyme for AD therapy.

Design and Hardware Implementation of a New Chaotic Secure Communication Technique.

In this paper, a scheme for chaotic modulation secure communication is proposed based on chaotic synchronization of an improved Lorenz system. For the first time, the intensity limit and stability of the transmitted signal, the characteristics of broadband and the requirements for accuracy of electronic components are presented by Multisim simulation. In addition, some improvements are made on the measurement method and the proposed experimental circuit in order to facilitate the experiments of chaotic synchronization, chaotic non-synchronization, experiment without signal and experiment with signal. To illustrate the effectiveness of the proposed scheme, some numerical simulations are presented. Then, the proposed chaotic secure communication circuit is implemented through analog electronic circuit, which is characterized by its high accuracy and good robustness.

MicroRNA-146a represses LRP2 translation and leads to cell apoptosis in Alzheimer's disease.

MicroRNA regulation of transcript expression has been reported in patients with Alzheimer's disease (AD). Here, we investigate the role of microRNA-146a (miRNA-146a), a brain-enriched miRNA, which is upregulated in AD patients. Through analysis of predicted targets of miRNA-146a, low-density lipoprotein receptor-related protein-2 (Lrp2), a member of the LDLR family that is known to play a protective role in AD, was identified. Overexpression of miRNA-146a in SH-SY5Y cells significantly decreased Lrp2 expression, resulting in a reduction of Akt activation and induction of proapoptotic caspase-3, thereby increasing cell apoptosis. Thus, specific miRNA-146a regulation may contribute to AD by downregulating the Lrp2/Akt pathway.

MicroRNA-146a suppresses ROCK1 allowing hyperphosphorylation of tau in Alzheimer's disease.

MicroRNA-146a is upregulated in the brains of patients with Alzheimer's disease (AD). Here, we show that the rho-associated, coiled-coil containing protein kinase 1 (ROCK1) is a target of microRNA-146a in neural cells. Knockdown of ROCK1 mimicked the effects of microRNA-146a overexpression and induced abnormal tau phosphorylation, which was associated with inhibition of phosphorylation of the phosphatase and tensin homolog (PTEN). The ROCK1/PTEN pathway has been implicated in the neuronal hyperphosphorylation of tau that occurs in AD. To determine the function of ROCK1 in AD, brain tissue from 17 donors with low, intermediate or high probability of AD pathology were obtained and analyzed. Data showed that ROCK1 protein levels were reduced and ROCK1 colocalised with hyperphosphorylated tau in early neurofibrillary tangles. Intra-hippocampal delivery of a microRNA-146a specific inhibitor (antagomir) into 5xFAD mice showed enhanced hippocampal levels of ROCK1 protein and repressed tau hyperphosphorylation, partly restoring memory function in the 5xFAD mice. Our in vitro and in vivo results confirm that dysregulation of microRNA-146a biogenesis contributes to tau hyperphosphorylation and AD pathogenesis, and inhibition of this microRNA could be a viable novel in vivo therapy for AD.