[Prenatal screening and prenatal diagnosis clinical laboratory diagnostic pathway].

Congenital defects and genetic diseases in the fetus are the focus of prenatal screening and prenatal diagnosis. Obstetrics and gynecology, pediatrics, medical imaging (ultrasound and magnetic resonance imaging), clinical laboratory, pathology, and other disciplines are mostly involved in this multidisciplinary work on maternal and infant health care, which aims to prevent birth defects in strict accordance with laws, regulations, and pertinent industry standards, such as the Notice of the National Health Commission on Issuing the Basic Standards for Prenatal Screening Technical Medical Institutions and the Basic Standards for Prenatal Diagnosis Technical Medical Institutions (Guowei Maternal and Child Letter [2019] No. 297). To further support the implementation of prenatal screening and diagnosis work and streamline workflow, this study has compiled the timing, inspection, and testing procedures of various projects in each link from the standpoint of the disease clinical laboratory diagnostic pathway. This approach improves communication amongst various disciplines in prenatal screening and diagnosis work and offers clinical service quality, and it also helps improve the standard of the birth population and prevent and controll severe birth defects.

High-Flux Neutron Generator Based on Laser-Driven Collisionless Shock Acceleration.

A novel compact high-flux neutron generator with a pitcher-catcher configuration based on laser-driven collisionless shock acceleration (CSA) is proposed and experimentally verified. Different from those that previously relied on target normal sheath acceleration (TNSA), CSA in nature favors not only acceleration of deuterons (instead of hydrogen contaminants) but also increasing of the number of deuterons in the high-energy range, therefore having great advantages for production of high-flux neutron source. The proof-of-principle experiment has observed a typical CSA plateau feature from 2 to 6 MeV in deuteron energy spectrum and measured a forward neutron flux with yield 6.6×10^{7} n/sr from the LiF catcher target, an order of magnitude higher than the compared TNSA case, where the laser intensity is 10^{19} W/cm^{2}. Self-consistent simulations have reproduced the experimental results and predicted that a high-flux forward neutron source with yield up to 5×10^{10} n/sr can be obtained when laser intensity increases to 10^{21} W/cm^{2} under the same laser energy.

[A deep learning segmentation model for detecting caries in molar teeth].

This study aimed to build a home use deep learning segmentation model to identify the scope of caries lesions. A total of 494 caries photographs of molars and premolars collected via endoscopy were selected. Subsequently, these photographs were labeled by physicians and underwent segmentation training by using DeepLabv3+, and then verification and evaluation were performed. The mean accuracy was 0.993, the sensitivity was 0.661, the specificity was 0.997, the Dice coefficient was 0.685, and the intersection over union (IoU) was 0.529. Therefore, the present deep learning segmentation model can identify and segment the scope of caries.

Giant Isolated Attosecond Pulses from Two-Color Laser-Plasma Interactions.

A new regime in the interaction of a two-color (ω,2ω) laser with a nanometer-scale foil is identified, resulting in the emission of extremely intense, isolated attosecond pulses-even in the case of multicycle lasers. For foils irradiated by lasers exceeding the blow-out field strength (i.e., capable of fully separating electrons from the ion background), the addition of a second harmonic field results in the stabilization of the foil up to the blow-out intensity. This is then followed by a sharp transition to transparency that essentially occurs in a single optical cycle. During the transition cycle, a dense, nanometer-scale electron bunch is accelerated to relativistic velocities and emits a single, strong attosecond pulse with a peak intensity approaching that of the laser field.

[Operative treatment of delayed acetabular fractures through combined anterior and Kocher-Langenbeck approaches].

Objective: To discuss the clinical outcomes of treating delayed acetabular fractures by combined anterior and posterior approach. Methods: A retrospective analysis was conducted of 31 delayed acetabular fractures from February 2012 to February 2017 in the First Affiliated Hospital of Chongqing Medical University, including 18 males and 13 females with age of 48.5 years(23 to 67 years) .The injury to the operation time was 35.9 days(22 to 183 days). Of these 31 cases, there were 6 cases of transverse and posterior wall fracture, 8 cases with anterior column+ posterior half transverse fracture, 12 cases with double column fracture and 5 cases of "T" type fracture according to Letournel-Judet classification.All fractures were treated combined anterior and Kocher-Langenbeck approaches, including 13 cases of ilioinguinal approach+ Kocher-Langenbeck(K-L approach), 4 cases of extensile acetabular approach, 7 cases of stoppa approach + K-L approach and 7 cases of side rectus femoris approach.Correlation was analyzed by Pearson correlation regression testing. Results: Follow up to August 2017, all patients were followed up with 36.0 months(from 6 to 55 months). As calculated, the restorational effect was positively with result of the X-ray film and the clinical effect(r=0.823, 0.856; both P<0.05). The evaluation was conducted with Matta's reduction criteria: there were 11 cases classified as anatomic reduction(35.5%), 13 cases as satisfactory reduction(41.9%), and 7 cases as unsatisfactory reduction(22.6%). Excellent and good rate was 77.4%. Functional reductions were categorized by the standard of Matta hip score: 8 excellent cases(25.8%), 11 good cases(35.5%), 8 fail cases(25.8%), and 4 poor cases(12.9%). Conclusion: The treatment of delayed acetabular fracture by combined anterior and posterior approach can fully exposure the anterior and posterior acetabular fcloumns, which is beneficial to the release and fixation of the old acetabular fractures.

EFFECTS OF Wnt / ß-CATENIN SIGNALING PATHWAY AND STAR D7 ON TESTOSTERONE SYNTHESIS.

BACKGROUND: This study aimed to assess the mechanism through which Wnt/ beta - catenin signaling pathway, and StarD7, prometes testosterone synthesis, and to explore a new pathway for the regulation of testosterone synthesis. ANIMALS AND METHODS: Leydig cells were isolated from male Sprague-Dawley rats divided into four groups and treated with Annexin 5 in concentration of 0, 0.1, 1 and 10 nmol/L. Testosterone secretion, expression of StarD7, StarD7 mRNA, ß-catenin and changes of ß - catenin localization in Leydig cells of testis of rats were tested in the four groups. RESULTS: mRNA and protein levels of StarD7 and ß-catenin increased significantly, upon stimulation with 1 nmol/L annexin 5. Accumulation of ß-catenin inside the cells and the nucleus, was observed by immunofluorescence staining, in cells treated with annexin 5. These findings indicate a possible role of StarD7 and ß-catenin in the process of annexin5-mediated stimulation of testosterone synthesis. CONCLUSIONS: Wnt/ß-catenin signaling pathway and StarD7 are involved in the process of annexin5 stimulation of testosterone synthesis. Activation of Wnt/ ß-catenin signaling pathway by Annexin5, and increase in StarD7 expression lead to elevated expression of key regulatory enzymes in testosterone synthesis, thus promoting testosterone synthesis.

Association of genetic polymorphisms of de novo nucleotide biosynthesis with increased CHD susceptibility in the northern Chinese population.

Congenital heart disease (CHD) is one of most prevalent birth defects in the world. However, the underlying molecular mechanism(s) have not been fully understood. Here we report that increased CHD susceptibility is associated with genetic polymorphisms for de novo nucleotide biosynthesis in northern Chinese population, which has been reported with lower plasma folate levels. Nine tagSNPs of four genes (GART, ATIC, MTHFD1 and SHMT1) in de novo nucleotide biosynthesis were sequenced in 802 sporadic CHD patients and 1093 controls from two Han Chinese populations, located in north China (Shandong) and South China (Shanghai), respectively. Six SNPs were found to be significantly associated with CHDs or septation defects only in the Shandong population dataset, but none displayed significant association with any CHDs in the Shanghai population dataset as well as in the combined dataset. We also showed that the minor A allele of rs7279549 in GART reduced transcriptional activity and displayed lower affinity for unknown transcription factor(s), demonstrating the allele is a functional risk factor for CHD in Shandong population. Our study indicates that dysregulation of de novo nucleotide biosynthesis pathway may conditionally contribute to CHD pathogenesis in northern Chinese.

Achieving Stable Radiation Pressure Acceleration of Heavy Ions via Successive Electron Replenishment from Ionization of a High-Z Material Coating.

A method to achieve stable radiation pressure acceleration (RPA) of heavy ions from laser-irradiated ultrathin foils is proposed, where a high-Z material coating in front is used. The coated high-Z material, acting as a moving electron repository, continuously replenishes the accelerating heavy ion foil with comoving electrons in the light-sail acceleration stage due to its successive ionization under laser fields with Gaussian temporal profile. As a result, the detrimental effects such as foil deformation and electron loss induced by the Rayleigh-Taylor-like and other instabilities in RPA are significantly offset and suppressed so that stable acceleration of heavy ions are maintained. Particle-in-cell simulations show that a monoenergetic Al^{13+} beam with peak energy 3.8 GeV and particle number 10^{10} (charge >20 nC) can be obtained at intensity 10^{22} W/cm^{2}.

[Expression of macrophage migration inhibitory factor gene in placenta tissue and its correlation with gestational diabetes mellitus].

Objective: To investigate the relationship between the expression of macrophage migration inhibitory factor (MIF) gene and the incidence of gestational diabetes mellitus (GDM) in Chinese Han population in northern China. Method: This study was consisted of 126 GDM women and 150 cases of healthy subjects who came from the obstetrics department of Maternity Hospital of Qingdao University and Maternity and Child Care Hospital of Donggang District of Rizhao. The protein expression of MIF in placenta tissue was detected by Western blot method. The blood glucose, insulin levels and other clinical physicochemical index were tested. The differences of MIF, fasting blood-glucose (FBG), fasting insulin (FIN) and the homeostasis model assessment of insulin resistance (HOMA-IR) were compared between the two groups of pregnant women. Result: The level of MIF protein in GDM group (0.85±0.10) was higher than that in healthy pregnant group (0.12±0.09), with significant difference (P<0.001). Insulin resistance index in GDM group were higher than that in healthy pregnant group, with significant difference (P<0.001). Conclusion: The expression of MIF in placental tissues of GDM women was increased and correlated with insulin resistance in GDM patients, suggesting that MIF may play an important role in the occurrence and development of GDM.

Generation of Superponderomotive Electrons in Multipicosecond Interactions of Kilojoule Laser Beams with Solid-Density Plasmas.

The interaction of a multipicosecond, kilojoule laser pulse with a surface of a solid target has been shown to produce electrons with energies far beyond the free-electron ponderomotive limit m_{e}c^{2}a_{0}^{2}/2. Particle-in-cell simulations indicate that an increase in the pulse duration from 1 to 10 ps leads to the formation of a low-density shelf (about 10% of the critical density). The shelf extends over 100 µm toward the vacuum side, with a nonstationary potential barrier forming in that area. Electrons reflected from the barrier gain superponderomotive energy from the potential. Some electrons experience an even greater energy gain due to ponderomotive acceleration when their "dephasing rate" R=γ-p_{x}/m_{e}c drops well below unity, thus increasing acceleration by a factor of 1/R. Both 1D and 2D simulations indicate that these mechanisms are responsible for the generation of extensive thermal distributions with T_{e}>10 MeV and a high-energy cutoff of hundreds of MeV.

Self-Consistent Simulation of Transport and Energy Deposition of Intense Laser-Accelerated Proton Beams in Solid-Density Matter.

The first self-consistent hybrid particle-in-cell (PIC) simulation of intense proton beam transport and energy deposition in solid-density matter is presented. Both the individual proton slowing-down and the collective beam-plasma interaction effects are taken into account with a new dynamic proton stopping power module that has been added to a hybrid PIC code. In this module, the target local stopping power can be updated at each time step based on its thermodynamic state. For intense proton beams, the reduction of target stopping power from the cold condition due to continuous proton heating eventually leads to broadening of the particle range and energy deposition far beyond the Bragg peak. For tightly focused beams, large magnetic field growth in collective interactions results in self-focusing of the beam and much stronger localized heating of the target.

An enzyme-linked immunosorbent assay for detection of pyrene and related polycyclic aromatic hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) can form DNA-binding compounds that show genotoxicity and carcinogenicity. Pyrene, as a PAH, was covalently linked to carrier protein bovine serum albumin and ovalbumin. A monoclonal antibody (McAb) was produced that showed high cross-reactivity values with chrysene (169.73%), benzo[a]pyrene (693.34%), benzo[a]anthracene (16.36%), and indeno[1,2,3-cd]pyrene (40.96%) and showed no significant cross-reactivity values with other homologues (<0.1%). A competitive enzyme-linked immunosorbent assay (ELISA) was developed for detection of pyrene and some homologues in water samples. The detection limit of the assay was 65.08 pg ml(-1). The average recoveries of PAHs from tap water, lake water, and mineral water were 99.13, 99.74, and 99.19%, respectively, indicating that matrices of water samples do not interfere with the assay. The results demonstrated that the developed ELISA seems to be a potential method for monitoring of pyrene and some homologous PAHs in water samples.

Cross-priming amplification targeting the coagulase gene for rapid detection of coagulase-positive Staphylococci.

AIMS: To develop and evaluate cross-priming amplification (CPA) combined with immuno-blotting for the detection of coagulase-positive Staphylococci including Staphylococcus aureus. METHODS AND RESULTS: Twenty-four sets of cross and detection primers were designed according to four sequences of coagulase gene in Staph. aureus. The most specific primer pair was screened out for the next amplification and interaction. The specificity was evaluated in a total of 53 species of Staph. aureus and non-Staph. aureus. Two red lines indicating positive were always observed on the BioHelix Express strip for 12 subspecies of Staph. aureus. In contrast, only one signal line showing negative results was detected in all of non-Staph. aureus samples. The limit of detection (LOD) of CPA was 3·6 ± 2·7 fg for the genomic DNA, which is about 100 and 10 times sensitive than those of PCR and loop-mediated isothermal amplification respectively. For the pure culture of Staph. aureus and milk powders, the LODs of CPA were about 1·34 CFU per reaction and 5·2 ± 3·7 CFU per 100 g of milk powder respectively. The CPA method was also successfully applied to evaluate the contamination of Staph. aureus in 318 samples of daily food. CONCLUSIONS: CPA is a very sensitive and rapid method to detect Staph. aureus by simple laboratory instrument. SIGNIFICANCE AND IMPACT OF THE STUDY: It is the first report on the application of the CPA with immuno-blotting for detection of coagulase-positive Staphylococci including Staph. aureus.

Efficiency of live attenuated and inactivated rabies viruses in prophylactic and post exposure vaccination against the street virus strain.

Rabies remains an enigmatic and widely discussed global infectious disease and causes an increasing number of deaths. The currently used highly effective prophylactic and post exposure (p.e.) vaccination depends solely upon inexpensive, effective and safe vaccines to counteract the spread of the disease. In this study, the potential of an attenuated Chinese rabies vaccine (SRV9) strain in prophylactic and p.e. vaccination against the street strain of rabies virus (RV) was evaluated in mice. Prophylactic vaccination consisting of one intramuscular (i.m.) dose of SRV9 protected 100% of mice from intracerebral (i.c.) challenge with a lethal dose of the street virus. The latter was detected in the brain of mice at day 6 post challenge by RT-PCR. Post exposure vaccination was performed at days 1, 2, 3, 4, 5 and 6 post infection (p.i.) with either SRV9 or inactivated rabies vaccine. The survival rates after i.m. inoculation of SRV9 at the indicated days were 70%, 50%, 30%, 20%, 10%, and 0%, respectively; the corresponding survival rates for the inactivated rabies vaccine were 30%, 20%, 10%, 0%, 0%, and 0%, respectively. However, 100%, 90%, 70%, 50%, 20%, 10%, and 10% of mice survived after i.c. inoculation of SRV9 at the indicated days. The increased permeability of the blood-brain barrier and the infiltration of CD19+ B cells into the central nervous system after i.c. inoculation of SRV9 are regarded as prerequisites for the clearance of the street virus. The obtained data suggest that SRV9 is a promising candidate for prophylactic and p.e. vaccination against rabies infection and that it exhibits a potential for the control of rabies in China.

Frequency and clinical outcomes of ESKAPE bacteremia in solid organ transplantation and the risk factors for mortality.

BACKGROUND: Although bacteremias caused by the 6 ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) have recently been highlighted as a serious complication in solid organ transplant (SOT), more information is urgently needed. We sought to investigate the frequency and clinical outcomes of ESKAPE bacteremia in SOT and determine the risk factors for mortality. METHODS: A retrospective analysis of bacteremia after SOT was reviewed. Risk factors for mortality caused by ESKAPE bacteremia were identified. RESULTS: Eighty-four episodes of bacteremia were caused by ESKAPE strains. Of these strains, 41 were caused by resistant ESKAPE (rESKAPE) organisms. The only factor for bacteremia-related mortality independently associated with ESKAPE was septic shock (odds ratio [OR] = 21.017, 95% confidence interval [CI] = 5.038-87.682, P < 0.001). The factors for bacteremia-related mortality independently associated with rESKAPE bacteremia were septic shock (OR = 16.558, 95% CI = 6.620-104.668, P = 0.003) and age ≥40 years (OR = 7.521, 95% CI = 1.196-47.292, P = 0.031). CONCLUSIONS: To improve the outcomes of transplantation, more effective therapeutic treatments are of paramount importance when older SOT recipients with bacteremia due to ESKAPE/rESKAPE organisms present with septic shock.

Mediating Effect of the NLR on the Relationship Between HbA1c and Left Atrial Stiffness in Overweight Patients With Hypertension.

BACKGROUND: We aimed to investigate the association between hemoglobin A1c (HbA1c) and left atrial (LA) stiffness in patients with hypertension and to explore the mediating effect of the neutrophil/lymphocyte ratio (NLR) on this association. METHODS: Essential hypertensive patients (n = 292) aged 18-83 years were enrolled and divided into two groups based on the LA stiffness index (LASI): Group I (LASI ≤ 0.32, n = 146) and Group II (LASI > 0.32, n = 146). The LASI was defined as the ratio of early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') to LA reservoir strain. Multivariate linear regression analysis was performed to determine the independent predictors of the LASI. RESULTS: Age, BMI, SBP, HbA1c, CRP, and NLR were significantly greater in Group II than in Group I (P < 0.05). Additionally, Group II had a greater LA volume index (LAVI), left ventricular mass index (LVMI), and early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') and lower LA reservoir, conduit, and booster pump strains than Group I (P < 0.001). Univariate and multivariate linear regression models revealed that age, SBP, HbA1c, and the NLR were independently associated with the LASI. Further mediation analysis was performed to determine the mediating effect of the NLR on the association between HbA1c and the LASI and revealed that the NLR had a mediating role only in overweight hypertensive patients, and the proportion of the mediating effect was 21.9%. CONCLUSIONS: The NLR was independently correlated with the LASI and played a mediating role in the relationship between HbA1c and the LASI in overweight hypertensive patients.

Mechanism studies for relativistic attosecond electron bunches from laser-illuminated nanotargets.

To find a way to control the electron-bunching process and the bunch-emitting directions when an ultraintense, linearly polarized laser pulse interacts with a nanoscale target, we explored the mechanisms for the periodical generation of relativistic attosecond electron bunches. By comparing the simulation results of three different target geometries, the results show that for nanofoil target, limiting the transverse target size to a small value and increasing the longitudinal size to a certain extent is an effective way to improve the total electron quantity in a single bunch. Then the subfemtosecond electronic dynamics when an ultrashort ultraintense laser grazing propagates along a nanofoil target was analyzed through particle-in-cell simulations and semiclassical analyses, which shows the detailed dynamics of the electron acceleration, radiation, and bunching process in the laser field. The analyses also show that the charge separation field produced by the ions plays a key role in the generation of electron bunches, which can be used to control the quantity of the corresponding attosecond radiation bunches by adjusting the length of the nanofoil target.

Dominance of radiation pressure in ion acceleration with linearly polarized pulses at intensities of 10(21) W cm(-2).

A novel regime is proposed where, by employing linearly polarized laser pulses at intensities 10(21) W cm(-2) (2 orders of magnitude lower than discussed in previous work [T. Esirkepov et al., Phys. Rev. Lett. 92, 175003 (2004)]), ions are dominantly accelerated from ultrathin foils by the radiation pressure and have monoenergetic spectra. In this regime, ions accelerated from the hole-boring process quickly catch up with the ions accelerated by target normal sheath acceleration, and they then join in a single bunch, undergoing a hybrid light-sail-target normal sheath acceleration. Under an appropriate coupling condition between foil thickness, laser intensity, and pulse duration, laser radiation pressure can be dominant in this hybrid acceleration. Two-dimensional particle-in-cell simulations show that 1.26 GeV quasimonoenergetic C(6+) beams are obtained by linearly polarized laser pulses at intensities of 10(21) W cm(-2).

Ion acceleration in multispecies targets driven by intense laser radiation pressure.

The acceleration of ions from ultrathin foils has been investigated by using 250 TW, subpicosecond laser pulses, focused to intensities of up to 3 × 10(20) W cm(-2). The ion spectra show the appearance of narrow-band features for protons and carbon ions peaked at higher energies (in the 5-10 MeV/nucleon range) and with significantly higher flux than previously reported. The spectral features and their scaling with laser and target parameters provide evidence of a multispecies scenario of radiation pressure acceleration in the light sail mode, as confirmed by analytical estimates and 2D particle-in-cell simulations. The scaling indicates that monoenergetic peaks with more than 100 MeV/nucleon are obtainable with moderate improvements of the target and laser characteristics, which are within reach of ongoing technical developments.