[Report content and prenatal diagnosis of non-invasive prenatal testing for sex chromosome aneuploidy].

Objective: To analyze the report content, the methods and results of prenatal diagnosis of high risk of sex chromosome aneuploidy (SCA) in non-invasive prenatal testing (NIPT). Methods: A total of 227 single pregnancy pregnant women who received genetic counseling and invasive prenatal diagnosis at Drum Tower Hospital Affiliated to the Medical School of Nanjing University from January 2015 to April 2022 due to the high risk of SCA suggested by NIPT were collected. The methods and results of prenatal diagnosis were retrospectively analyzed, and the results of chromosome karyotype analysis and chromosome microarray analysis (CMA) were compared. The relationship between NIPT screening and invasive prenatal diagnosis was analyzed. Results: (1) Prenatal diagnosis methods for 277 SCA high risk pregnant women included 73 cases of karyotyping, 41 cases of CMA and 163 cases of karyotyping combined with CMA, of which one case conducted amniocentesis secondly for further fluorescence in situ hybridization (FISH) testing. Results of invasive prenatal diagnosis were normal in 166 cases (59.9%, 166/277), and the abnormal results including one case of 45,X (0.4%, 1/277), 18 cases of 47,XXX (6.5%, 18/277), 36 cases of 47,XXY (13.0%, 36/277), 20 cases of 47,XYY (7.2%, 20/277), 1 case of 48,XXXX (0.4%, 1/277), 20 cases of mosaic SCA (7.2%, 20/277), 5 cases of sex chromosome structural abnormality or large segment abnormality (1.8%, 5/277), and 10 cases of other abnormalities [3.6%, 10/277; including 9 cases of copy number variation (CNV) and 1 case of balanced translocation]. Positive predictive value (PPV) for SCA screening by NIPT was 34.7% (96/277). (2) Among the 163 cases tested by karyotyping combined with CMA, 11 cases (6.7%, 11/163) showed inconsistent results by both methods, including 5 cases of mosaic SCA, 1 case of additional balanced translocation detected by karyotyping and 5 cases of additional CNV detected by CMA. (3) NIPT screening reports included 149 cases of "sex chromosome aneuploidy"(53.8%, 149/277), 54 cases of "number of sex chromosome increased" (19.5%, 54/277), and 74 cases of "number of sex chromosome or X chromosome decreased" (26.7%, 74/277). The PPV of "number of sex chromosome increased" and "number of sex chromosome or X chromosome decreased" were 72.2% (39/54) and 18.9% (14/74), respectively, and the difference was statistically significant (χ2=34.56, P<0.01). Conclusions: NIPT could be served as an important prenatal screening technique of SCA, especially for trisomy and mosaicism, but the PPV is comparatively low. More information of NIPT such as the specific SCA or maternal SCA might help improving the confidence of genetic counseling and thus guide clinic management. Multi technology platforms including karyotyping, CMA and FISH could be considered in the diagnosis of high risk of SCA by NIPT.

[Clinicopathological features and molecular characteristics of tall cell and hobnail variants of papillary thyroid carcinoma].

Objective: To investigate the clinicopathological and molecular genetic characteristics of tall cell variant and hobnail variant of papillary thyroid carcinoma (PTC). Methods: Twenty-one cases of tall cell variant (TCV-PTC) of PTC (TCV-PTC) and ten cases of hobnail variant of PTC (HV-PTC), as the highly aggressive group, were collected from Xuanwu Hospital from August 2009 to August 2015. Twenty-two cases of follicular variant and 21 classical PTC cases were included as control. Relevant clinical and pathologic data were obtained, and in some cases, paraffin samples were selected for gene mutation spectrum analysis using second generation sequencing. Results: There were 18 males and 56 females; 57 patients were younger than 55 years of age, and 17 patients were 55 years or older. The mean tumor size was 1.6 cm for the high-aggressive group (TCV-PTC and HV-PTC), 1.1 cm for the follicular subtype, and 1.6 cm for the classical type. There were 54 cases with thyroid capsule invasion, 24 cases with extra-thyroidal invasion, and 45 patients with lymph node metastases. Regional recurrence occurred in 7 cases, no recurrence in 54 cases, and 13 patients were lost to follow-up. The highly aggressive group was more likely to show extra-thyroidal invasion, lymph node metastases and recurrence than those with classical PTC (P<0.05). Within this cohort, BRAF V600E mutation was detected in 53 cases and TERT promoter mutation in 6 cases. Compared with the single mutation group and no mutation group, BRAF and TERT promoter co-mutation group was more commonly detected in older age, male, larger tumor size and more prone to extra-thyroid invasion (P<0.05). In addition, among BRAF and TERT co-mutation cases, the highly-aggressive group accounted for the highest proportion (5/6). Conclusions: TCV-PTC and HV-PTC, as highly-aggressive variants of PTC, show more aggressive biologic behavior (more lymph node metastasis, external thyroid invasion and recurrences) than the classical and follicular variants of PTC. Coexisting BRAF and TERT promoter mutations may be associated with invasive biologic behavior.

[Prospective cohort study of fetal nuchal translucency in first-trimester and pregnancy outcome].

Objective: To explore the relationship between fetal nuchal translucency (NT) in the first trimester and pregnancy outcome. Methods: A prospective cohort study was conducted in Nanjjing Drum Tower Hospital from December 2015 to December 2018, 4 958 singleton pregnant women were enrolled to screen fetal ultrasound structure and serology in the first trimester, ultrasound in the second trimester and neonatus physical examination 28 days after birth. According to the results of NT, 167 cases of fetus with increased NT (≥3.0 mm) and 4 791 cases of normal NT were divided, moreover, 86 cases with isolate increased NT and 81 cases of increased NT combined with structural abnormality. The prognosis of fetuses with different NT thickness was analyzed, and the pregnancy outcome of fetuses with isolate increased NT or combined with structural abnormality were analyzed. In the first trimester, if the fetal structure was abnormal or the serological screening result was high risk, the chromosomal microarray analysis (CMA) would be performed by chorionic villus sampling to determine the prenatal diagnosis. Results: (1) The pregnancy outcome for fetus of normal NT: there were 4 791 cases with normal NT. Totally, 4 726 cases with normal NT and no structural abnormalities were screened out in the firsttrimester. In this group, 5 cases of aneuploidies were diagnosed based on high risk of maternal serum biomarkers and 83 cases of structural abnormalities were screened out in the subsequent ultrasound scan and the neonatal examination. Another 65 cases with normal NT present complicated with structural anomalies were screened out in the first trimester and 4 cases were diagnosed as aneuploidies. (2) The pregnancy outcome for fetus of isolate increased NT: 66 (76.7%, 66/86) cases of isolated increased NT were performed CMA, 3 cases were diagnosed as trisomy 21 and terminated pregnancy. Another 4 cases were terminated pregnancy privately without cytogenetic diagnosis. No further anomalies were found in 79 cases till 6 to 21 months postnatally. (3) The pregnancy outcome for fetus of increased NT with structural anomalies: increased NT present with structural anomalies were screened out by detailed anomaly scan in the first trimester and 32 of them were confirmed as aneuploidies. In this group, 70 cases terminated pregnancy, 2 cases had spontaneous miscarriages and 9 cases had liveborns (1 newborn was found ventricular septal defect). (4) The pregnancy outcome for fetus of increased NT with or without structural anomalies: the percentage of aneuploidies in fetuses with isolated increased NT (3.5%, 3/86) was significantly lower than those with structural abnormalities (39.5%,32/81). The healthy survival rate in fetuses with isolated increased NT (91.9%,79/86) was significantly higher than those with structural abnormalities (9.9%, 8/81). Conclusions: A detailed first-trimester anomaly scan could improve prenatal screening efficiency of birth defects. Compared to the fetuses with increased NT combined with structural abnormalities, the healthy survival rate of fetuses with isolated increased NT based on detailed first-trimester anomaly scan is higher and the percentage of fetal aneuploidies is lower.

Detection of serum procalcitonin and hypersensitive C-reactive protein in patients with pneumonia and sepsis.

Sepsis, a systemic inflammatory response syndrome induced by infection, has high rates of morbidity and mortality. Pneumonia is a major cause for sepsis; however, pneumonia complicated by sepsis is a difficult clinical diagnosis. To assess the clinical relevance of serum procalcitonin (PCT) and hypersensitive C-reactive protein (hs-CRP) in early diagnosis of pneumonia complicated by sepsis, 220 patients with pneumonia who were admitted to hospital from July 2015 to July 2016 were enrolled in this study. The patients were divided into non-sepsis (N=82), mild sepsis (N=97), severe sepsis (N=23), and septic shock (N=18) groups. The patients were also divided into a survival group (N=186) and a death group (N=34) according to their prognosis at 2 weeks. The PCT and hs-CRP levels and Acute Physiology and Chronic Health Evaluation-II (APACHE-II) scores of the two groups were evaluated. The PCT level and APACHE-II score showed a progressively increasing tendency in the non-sepsis, mild sepsis, severe sepsis, and septic shock group; the differences between all pairs of groups were significant (P less than 0.05). The hs-CRP level was significantly lower in the non-sepsis group than in the other groups (P less than 0.05), but differences among the other groups were not significant (P>0.05). The areas under the receiver operating characteristic curves of PCT and hs-CRP for diagnosis of pneumonia complicated by mild and severe sepsis were 0.841 and 0.817, respectively. The optimal cut-off points for pneumonia and sepsis were ≥0.5 ng/mL and ≥55 mg/L, respectively; the sensitivity and specificity were 71.42% and 82.13%, and 75.04% and 53.61%, respectively. The sensitivity and specificity of diagnosis based on PCT and hs-CRP were 89.32% and 85.68%, respectively. PCT and hs-CRP are used to assess the severity of pneumonia in combination with sepsis in new-borns, but PCT is more strongly related to the severity of sepsis than is hs-CRP. Detection of PCT in combination with hs-CRP facilitates the early diagnosis of pneumonia and sepsis in new-borns, as well as monitoring of the treatment response and prediction of the prognosis.

Size-dependent mechanical properties of axial and radial mixed AlN/GaN nanostructure.

In this paper, continuum multiscale models are proposed to describe the size-dependent mechanical properties of two kinds of heterogeneous nanostructures: radially heterogeneous nanowires and longitudinally heterogeneous nanolaminates. In both cases, the continuum models involve additional surface/interface energies, which allow capturing size effects. Several models of imperfect interface models, like coherent and spring-layer ones, are shown to respectively capture the size effects, which are reported by first-principles calculations performed on heterogeneous nanostructures. In each case, a procedure is proposed to identify the parameters of the surface/interface model in the continuum framework, based on first-principles calculations performed on slab systems. The obtained continuum models allow avoiding full computations on atomistic models, which are not affordable for large sizes (diameters, layer thickness). An increase of the overall stiffness for both kinds of heterogeneous AlN/GaN nanostructures with the decrease of the dimensions is evidenced. The continuum models are then compared with full first-principles calculations to demonstrate their accuracy and their ability to capture size effects.

Four-dimensional micro-building blocks.

Four-dimensional (4D) printing relies on multimaterial printing, reinforcement patterns, or micro/nanofibrous additives as programmable tools to achieve desired shape reconfigurations. However, existing programming approaches still follow the so-called origami design principle to generate reconfigurable structures by self-folding stacked 2D materials, particularly at small scales. Here, we propose a programmable modular design that directly constructs 3D reconfigurable microstructures capable of sophisticated 3D-to-3D shape transformations by assembling 4D micro-building blocks. 4D direct laser writing is used to print two-photon polymerizable, stimuli-responsive hydrogels to construct building blocks at micrometer scales. Denavit-Hartenberg (DH) parameters, used to define robotic arm kinematics, are introduced as guidelines for how to assemble the micro-building blocks and plan the 3D motion of assembled chain blocks. Last, a 3D-printed microscaled transformer capable of changing its shape from a race car to a humanoid robot is devised and fabricated using the DH parameters to guide the motion of various assembled compartments.

[A case of Okur-Chung syndrome caused by CSNK2A1 gene variation and review of literature].

Objective: To summarize the clinical features and gene variation characteristics of a child with Okur-Chung syndrome caused by CSNK2A1 gene variation. Methods: The medical records of one patient who was diagnosed with Okur-Chung syndrome in Department of Pediatrics, Xiangya Hospital of Central South University in July 2018 were analyzed. Using "CSNK2A1" gene as the keyword, relevant information about CSNK2A1 gene was searched at CNKI, Wangfang Data, OMIM, PubMed, ClinVar, Decipher (until August 2018). The characteristics of CSNK2A1 gene variation and the clinical phenotype of children with Okur-Chung syndrome were summarized. Results: The boy, 1 year and 8 months old, was sent to hospital at the age of 1 year and 6 months because of delayed growth for more than 1 year. He was susceptible to cough while eating or drinking. He was also suffering from constipation and poor sleep. Physical examination showed that his body weight was 10.2 kg, microcephalus, broad nasal bridge, micrognathia and hypotonia were observed. Whole exome-sequencing test identified a de novo heterozygous variation c.524A>G (p.D175G) in CSNK2A1 gene. This was the first case report of CSNK2A1 gene variation in the mainland of China. So far, a total of 52 cases were reported worldwide (52 single nucleotide variants), including 35 cases in 7 articles, 9 cases in Decipher database and 14 cases in ClinVar database, 6 of which were also reported in PubMed. In previously reported 52 cases, there were 48 missense variants, whereas, splice and frameshift variations were found in 3 cases and 1 case, respectively. Among the variation sites, p.K198R was the most common sites (12 cases), followed by p.R47 (6 cases), p.R80H (4 cases) and p.S51 (4 cases). Among these 52 cases, only 27 cases have been elaborately described in other studies, so the clinical characteristics were summarized in 28 cases eventually (including 27 cases in the articles and this patient), 27 of whom presented severe intellectual disability or global development delay, 1 case with mild language development delay, and 19 had hypotonia; 8 had autism spectrum disorders, 5 had attention deficit hyperactivity disorder, and 9 had sleep problems. 20 had dysmorphic facial features, 10 of them had microcephalus. 16 had failure to thrive or short stature, 12 had gastrointestinal or oromotor problem, 5 had immunological problem, and 4 had skin abnormalities. Conclusions: The main clinical feature of patients with CSNK2A1 gene variations is intellectual disability with multiple systems involved, such as microcephalus, abnormal facial shape and hypotonia. The variation of CSNK2A1 gene is the cause of Okur-Chung syndrome. Missense variation is the main cause, and P. K198R is the hotspot variation.

CA916798 affects growth and metastasis of androgen-dependent prostate cancer cells.

OBJECTIVE: Abnormal activation of androgen receptor (AR) signaling pathway is a critical pathogenic mechanism and therapeutic target for prostate cancer (PCa). The CA916798 is a tumor-associated gene and may be regulated by the androgen-AR pathway. This study aims to investigate the function of CA916798 in the growth and metastasis of androgen-dependent PCa cells. MATERIALS AND METHODS: CA916798 expression in PCa cell lines was investigated. LNCap cells were divided into 4 groups: LNCap, LNCap+ Dihydrotestosterone (DHT), LNCap+DHT+siCA916798, and LNCap+DHT+siRA group. CA916798 expressions in LNCap cells treated with siCA917698 or siAR were examined. The viability, apoptosis, migration, and invasion of PCa cells were examined. Dual luciferase and ChIP assays were used to examine the interaction between the AR and CA916798. RESULTS: Endogenous CA916798 mRNA levels in PC3 cells were significantly higher than those in LNCap cells (p < 0.05). However, CA916798 was androgen-sensitive in LNCap cells, but not in PC-3 cells. Dual luciferase and ChIP assays showed that AR could specifically bind to the promoter regions of the CA916798. Knockdown of CA916798 (LNCap+DHT+siCA916798) and AR (LNCap+DHT+siAR) resulted in decreased cell viability, migration, and invasion, while it induced apoptosis and G1 cell cycle arrest in LNCap cells. CONCLUSIONS: DHT could initiate the transcription of CA916798, which further mediates the androgen-AR signaling pathway-dependent cell growth and metastasis of the prostate cancer cell line LNCap.

Texture evolution and mechanical behaviour of irradiated face-centred cubic metals.

A physically based theoretical model is proposed to investigate the mechanical behaviour and crystallographic texture evolution of irradiated face-centred cubic metals. This model is capable of capturing the main features of irradiated polycrystalline materials including irradiation hardening, post-yield softening and plasticity localization. Numerical results show a good agreement with experimental data for both unirradiated and irradiated stress-strain relationships. The study of crystallographic texture reveals that the initial randomly distributed texture of unirradiated metals under tensile loading can evolve into a mixture of [111] and [100] textures. Regarding the irradiated case, crystallographic texture develops in a different way, and an extra part of [110] texture evolves into [100] and [111] textures. Thus, [100] and [111] textures become dominant more quickly compared with those of the unirradiated case for the reason that [100] and [111]-oriented crystals have higher strength, and their plastic deformation behaviours are more active than other oriented crystals. It can be concluded that irradiation-induced defects can affect both the mechanical behaviour and texture evolution of metals, both of which are closely related to irradiation hardening.

Strain distributions in nano-onions with uniform and non-uniform compositions.

Nano-onions are ellipsoidal or spherical particles consisting of a core surrounded by concentric shells of nanometre size. Nano-onions produced by self-assembly and colloidal techniques have different structures and compositions, and thus differ in the state of strains. The mismatch of the thermal expansion coefficients and lattice constants between neighbouring shells induces stress/strain fields in the core and shells, which in turn affect their physical/mechanical properties and/or the properties of the composites containing them. In this paper, the strains in embedded and free-standing nano-onions with uniform and non-uniform compositions are studied in detail. It is found that the strains in the nano-onions can be modified by adjusting their compositions and structures. The results are useful for the band structure engineering of semiconductor nano-onions.

Mechanical properties for irradiated face-centred cubic nanocrystalline metals.

In this paper, a self-consistent plasticity theory is proposed to model the mechanical behaviours of irradiated face-centred cubic nanocrystalline metals. At the grain level, a tensorial crystal model with both irradiation and grain size effects is applied for the grain interior (GI), whereas both grain boundary (GB) sliding with irradiation effect and GB diffusion are considered in modelling the behaviours of GBs. The elastic-viscoplastic self-consistent method with considering grain size distribution is developed to transit the microscopic behaviour of individual grains to the macroscopic properties of nanocrystals (NCs). The proposed theory is applied to model the mechanical properties of irradiated NC copper, and the feasibility and efficiency have been validated by comparing with experimental data. Numerical results show that: (i) irradiation-induced defects can lead to irradiation hardening in the GIs, but the hardening effect decreases with the grain size due to the increasing absorption of defects by GBs. Meanwhile, the absorbed defects would make the GBs softer than the unirradiated case. (ii) There exists a critical grain size for irradiated NC metals, which separates the grain size into the irradiation hardening dominant region (above the critical size) and irradiation softening dominant region (below the critical size). (iii) The distribution of grain size has a significant influence on the mechanical behaviours of both irradiated and unirradiated NCs. The proposed model can offer a valid theoretical foundation to study the irradiation effect on NC materials.

[Immunohistochemical quantitative study of glial fibrillary acid protein and vimentin of astrocytomas].

Two different types of intermediate filaments, vimentin (VIM) and glial fibrillary acidic protein (GFAP) were studied by immunohistochemical quantitative analysis using image analyser in 25 cases of astrocytomas, grade II to IV. The results showed that the VIM and GFAP distribution patterns were similar in all cases of astrocytomas, but the expression of VIM in poorly differentiated astrocytoma (grade III and IV) being more frequent and intense than in well differentiated astrocytomas (grade II), the expression of GFAP in well differentiated astrocytomas (grade II) is more frequent and intense than in poorly differentiated astrocytomas (grade III and IV). We suggest that there is a negative relation between the reaction of GFAP and the degree of malignancy in astrocytomas and a positive correlation between reaction of VIM and the degree of malignancy in astrocytomas.

[High-performance dynamic ECG review & analysis system].

This paper describes the design of a high-performance dynamic ECG Review & Analysis system used for not only clinical diagnosis but also medical research. A new ECG pattern classifier with Variable Area Template is applied to improve the quantity of ECG analysis results, while the optimized software design ensures the other performances. The results show that this system has higher performance than the old ones and is valuable for medical research.

Graphene-coated atomic force microscope tips for reliable nanoscale electrical characterization.

Graphene single-layer films are grown by chemical vapor deposition and transferred onto commercially available conductive tips for atomic force microscopy. Graphene-coated tips are much more resistant to both high currents and frictions than commercially available, metal-varnished, conductive atomic force microscopy tips, leading to much larger lifetimes and more reliable imaging due to a lower tip-sample interaction.

Microstructures and mechanical properties of silks of silkworm and honeybee.

Natural silks as important biomaterials have wide applications in scaffolds for tissues, biocompatible coatings and drug delivery, etc. In this paper, we report on the microstructures and mechanical properties of honeybee and silkworm silks. The microstructures and mechanical properties of these natural silks are measured by environment scanning electron microscopy (ESEM), scanning probe microscopy (SPM), tensile tests, and nanoindentation. It is found that the honeybee silk appears as a single fiber with a circular cross-section and has a much finer and smoother texture than the silkworm silk. The honeybee silk exhibits a distinct linear and brittle elastic feature with an elastic modulus of 6.5GPa and a breaking strain of 3.8%, whereas the silkworm silk possesses a nonlinear and hierarchical failure character with an initial elastic modulus of 8.9GPa and a breaking strain of 15.7%. Moreover, the nanoindentation measurements show that the honeybee silk exhibits much less anisotropy than the silkworm silk. The ratio of the longitudinal modulus to the transverse modulus of the honeybee silk is 2.0, whereas that of the silkworm silk is 18.9. The different structural and mechanical properties of the honeybee and silkworm silks are likely a result of their specific biological functions.