OBJECTIVE: To assess the clinical value of non-invasive prenatal testing (NIPT) for the screening of trisomy and copy number variations (CNVs) of chromosomes 21, 18 and 13. METHODS: From January 2015 to December 2019, 40 628 pregnant women underwent NIPT testing using high-throughput sequencing and bioinformatics analysis to test the cell-free fetal DNA in maternal plasma. High-risk pregnant women underwent invasive prenatal diagnosis, while low-risk ones were followed up by telephone. RESULTS: The three most common indications included intermediate risk of serological screening, high risk of serological screening and advanced maternal age. Among all pregnant women, 257 cases were detected as trisomy 21, 18 and 13 (170, 49 and 38 cases, respectively). 227 cases chose invasive prenatal diagnosis, with respectively 122, 28 and 10 cases confirmed. The positive predictive value (PPV) was 81.33% (122/150), 65.12% (28/43), 29.41% (10/34), respectively. Two false negative cases of trisomy 18 were found during follow-up. Meanwhile, NIPT has detected 46 cases (15, 16 and 15 cases, respectively) CNVs on chromosomes 21, 18 and 13, among which 37 cases underwent invasive prenatal diagnosis. There were 5, 3 and 5 positive cases, which yielded a PPV of 41.67% (5/12), 25%(3/12) and 33.33%(5/15), respectively. Two other chromosome CNVs were accidentally discovered among the false positive samples. CONCLUSION The incidence of chromosomal abnormalities in the serological screening high-risk group was 52.02%, which was significantly higher than other groups. NIPT has a high sensitivity and specificity for the screening of trisomies 21, 18 and 13, while its accuracy for detecting CNVs of chromosomes 21, 18 and 13 needs to be improved. As a screening method, NIPT has a great clinical value, though there are still limitations of false positive and false negative results.Comprehensive pre- and post-test genetic counseling should be provided to the patients.
Aneuploidy ; Chromosome Disorders/genetics* ; Chromosomes ; DNA Copy Number Variations ; Down Syndrome/genetics* ; Female ; Humans ; Pregnancy ; Prenatal Diagnosis ; Trisomy/genetics* ; Trisomy 18 Syndrome/genetics*

Neutrophilic granule protein (NGP) was previously reported as a granular protein of neutrophils in mouse, but the function has not been known clearly. We found the presence of the possible signal peptide in NGP and validated this protein is circulating in the bloodstream. In our findings, NGP is being modified post-translationally in Golgi apparatus and endoplasmic reticulum, which is a universal character of secretory molecules with a signal peptide. The secreted NGP protein could be detected both in vitro and in vivo. NGP has sequence similarity with an antimicrobial protein cathelicidin, and we observed the aspect of inflammation of NGP. Interestingly, NGP interacts with the complex of LPS and LPS binding protein (LBP). This interaction blocks the binding of the complex of LPS and LBP to TLR4 and the downstream inflammatory signals. Furthermore, the inhibitory function of NGP against the inflammatory effect of LPS could be observed in both in vitro and in vivo. With these findings, we report NGP is a novel secretory protein to mask LPS and inhibit its function.
Animals ; Carrier Proteins ; Cytokines ; Endoplasmic Reticulum ; Golgi Apparatus ; In Vitro Techniques ; Inflammation ; Lipopolysaccharides ; Masks ; Mice ; Neutrophils ; Protein Binding ; Protein Sorting Signals

Objective: To evaluate the value of non-invasive prenatal testing (NIPT) in pregnancies with anomaly in prenatal screening. Methods: This was a retrospective study of 2 837 singleton pregnancies who performed NIPT indicated by isolated anomaly in prenatal screening at Guangdong Women and Children Hospital between November 2014 and August 2016. All pregnancies were divided into 3 groups by single indication: advanced maternal age ( AMA, ≥35), abnormal multiples of the median (MoM) in standard screening, increased nuchal translucency thickness (NT, 2.5-3.0 mm). High risk results were verified by prenatal diagnosis. Low risk cases were followed by a 22-26 week anatomical ultrasound examination. All of the cases were followed up and the performance of NIPT for every single indication was evaluated. Results: There were total of 2 837 pregnant women who underwent NIPT. Twenty-five of 2 448 pregnancies indicated by AMA had high risk results, among which 17 were confirmed by invasive genetic testing, except 1 case rejecting prenatal diagnosis. In 351 pregnant women with abnormal MoM, NIPT found 3 cases of sex chromosome aneuploidies (SCA) and 2 of them were validated by invasive prenatal diagnosis. Increased NT group included 38 cases, NIPT found 1 case of trisomy 21 which was consistent with karyotype analysis. For common aneuploidies and SCA, the performance of NIPT in the pregnant women who indicated by AMA, abnormal MoM and increased NT were as the follows: the sensitivity were 17/17, 2/2 and 1/1 respectively, the specificity were 99.7% (2 423/2 431), 99.7% (348/349) and 100%(37/37), the positive predictive value were 68% (17/25), 2/3 and 1/1, the negative predictive value were 100% (2 423/2 423), 100% (348/348) and 100% (38/38), respectively. By follow-up survey, a total of 8 cases of abnormal fetus were recorded in NIPT low-risk women, including 5 cases of termination of pregnancy due to abnormal ultrasound findings, 2 cases of abortion as a result of severe obstetric complications and 1 case of stillbirth. Conclusions To the pregnant women who indicated by advanced maternal age, abnormal MoM and increased NT (2.5-3.0 mm), NIPT had satisfactory performance for common aneuploidies, and also had potential value for SCA, resulting in a significant reduction in diagnostic procedures. However, for NIPT low-risk pregnancies, routine antenatal examination and anatomical ultrasound detection would be highly necessary to avoid missing abnormal fetuses.(Chin J Lab Med, 2018, 41: 509-513)

Objective To explore the plasma levels of soluble CD40 (sCD40) and soluble CD40 ligand (sCD40L) in the patients with Alzheimer’s disease (AD) and those with amnestic mild cognitive impairment (aMCI). Methods The levels of plasma sCD40 and sCD40L were measured in 20 patients with AD, 35 patients with aMCI, and 32 cognitively normal controls (NC) using commercially available ELISAs. The cognitive function of AD and aMCI patients was mea?sured by mini-mental state examination (MMSE). Results There were significant differences in plasma sCD40 among AD, aMCI and NC groups (P<0.05) as the medians (the upper and lower quartiles) of plasma levels were 123.3 (97.4, 149.5) pg/mL, 102.9 (63.6, 124.0) pg/mL and 70.66 (51.0, 90.8) pg/mL, respectively. There were significant differences in plasma sCD40L among AD, aMCI and NC groups (P<0.05) as plasma levels were 537.0 (316.0, 1134.0) pg/mL, 316.0 (190.0,546.0) pg/mL and 167.0 (107.5,478.0) pg/mL. A negative correlation between the plasma concentrations of sCD40L and the MMSE scores was found in aMCI patients (r=-0.736, P<0.001). Conclusions There are relevant chang?es of plasma sCD40 and sCD40L levels in patients with AD and aMCI. The present results suggest that plasma levels of sCD40 and sCD40L may be appropriate biomarkers for AD patients and indicate that CD40-CD40L signaling may be in?volved in AD pathophysiology.

Objective To investigate the sleep architecture in dementia with Lewy bodies (DLB),and study the sleep architecture and cognitive functions in DLB.Methods We described polysomnography (PSG) findings in 34 consecutive subjects diagnosed with DLB.All the patients underwent Mini-Mental State Examination (MMSE),Montreal Cognitive Assessment (MoCA),Clinical Dementia Rating (CDR) to quantify cognitive functions.Results (1)Sleep architecture analysis:DLB group compared to normal control group,the sleep period time (SPT) was reduced (P ＜ 0.05),total sleep time (TST) and sleep efficiency (SE) were decreased,total wake time (TWT) and wake after sleep onset (WASO) were increased,1 non-rapid eye movement (NREM) sleep (TS1),2NREM sleep (TS2),total NREM sleep (TNREMS),and REM sleep (TREMS) time were significantly decreased (P ＜0.01).(2)The DLB patients were divided into groups based on MMSE,MoCA,qnd CDR scores,the sleep architecture of each group was no significant difference (P ＞ 0.05).Conclusions Patients with DLB exists sleep architecture disorder.The cognitive functions and sleep architecture changes in patients with DLB have no obvious correlation.It is different from other degenerative dementia.

Objective Through the investigation of the iodine content in residents drinking water in Jianjiang River Basin of Guangdong,the scope and distribution of waterborne high iodine areas in this region were grasped so as to provide a basis for taking appropriate prevention and control measures.Methods All towns (streets) covering seven counties (cities,districts) of Jianjiang River Basin were selected by cross sectional screening method in 2012 and 2013,which were divided into mainly-investigated town (street) and generally-investigated town (street) according to the direction,geographical position and other situations of all branches of Jianjiang River.In each mainly-investigated town (street),two natural villages were selected according to the river direction and terrain conditions,and one water sample was collected from each village.In each generally-investigated town (street),one administrative village was selected respectively according to the locations (east,west,south,north and middle);two natural villages were selected from each administrative village,and one water sample was collected from each natural village.The water supply types of each natural village were investigated,including centralized water supply,decentralized water supply and river (reservoir) water.If the iodine content of the water samples was higher than 100 μg/L in the natural villages,then 10％ more water samples were collected.The inductive coupling plasma mass spectroscopy (ICP-MS) was adopted for water iodine detection.Results A total of 3 583 residents drinking water samples from Jianjiang River Basin were investigated,and the median of water iodine was 15.1 μg/L;the median of water iodine in reservoirs,river,mountain spring,well water was 12.1,9.8,2.5 and 18.6 μg/L,respectively.Iodine content of 341 water samples was ＞ 100 μg/L,accounting for 9.5％;228 water samples were ＞ 150 μg/L,accounting for 6.4％;58 water samples were more than 300 μg/L,accounting for 1.6％.The water samples with iodine content higher than 100 μg/L were all from decentralized well water.There were 18 natural villages which could be determined as the waterborne high iodine areas (water iodine ＞ 150 μg/L);they were distributed in 16 administrative villages in 14 towns (streets) of 5 counties (cities,districts) and had a registered population of 23 915 in total.The difference of water iodine between the 5 counties (cities,districts) in middle and lower reaches of Jianjiang River Basin (24.7,28.6,20.5,23.2,24.0 μg/L) and the 2 counties (cities,districts) in upper reaches (12.0,10.9 μg/L) was statistically significant (Z =13.5,P ＜ 0.05);the difference of water iodine between coastal and non-coastal areas (12.5 vs.5.9 μg/L) was statistically significant (Z =6.1,P ＜ 0.05).Conclusions The iodine content in surface water of Jianjiang River Basin is generally lower;,the high water iodine phenomenon dispersedly occurs in the underground water (well water),and the iodine content is different in different areas;the iodine content of the middle and lower reaches is higher than that of the upper reach,and the iodine content of the coastal alluvial areas is higher than that of the non-coastal areas.The natural villages with waterborne high iodine are spottily distributed in the coastal areas of all backbones and branches of Jianjiang River,but not connected together basically.

BACKGROUND:Calcium phosphate has the similar mineral component of natural bones with good bioactivity, osteoconductivity and degradability. It has been widely used in bone defect repair and coatings of implants. OBJECTIVE:To review the major properties of different-phase calcium phosphate and to summarize the application of calcium phosphate in scaffolds for osteochondral tissue engineering. METHODS:A computer-based search of PubMed, CNKI and VIP database was performed for relevant articles published from January 2000 to February 2015 with the key words of “osteochondral; calcium phosphate (including hydroxyapatite, tricalcium phosphate, calcium polyphosphate); tissue engineering” in Chinese and English, respectively. RESULTS AND CONCLUSION:Since the calcium phosphate has a variety of phases and crystaline types, a variety of materials with different structure and size can be obtained using different techniques, such as hydroxyapatite, tricalcium phosphate, calcium polyphosphate, amorphous calcium phosphate. These materials have some differences in their biological and mechanical properties, and hydroxyapatite is the most widely used. Biocomposite scaffolds with calcium phosphates appeared to have promising potential in osteochondral tissue engineering.

Objective To investigate the biosecurity and biocompatibility of small intestinal submucosa (SIS) as scaffold for tissue engineering and to explore the possibility to induce synovial mesenchymal stem cells (SMSCs) differentiate into cartilage with SIS as the scaffold and SMSCs as the seed cells. Methods The SMSCs were isolated and cultured from the synovial mem-brane of knee joints of rabbits by a conventional method. The SIS was harvested from pigs according to the physical method and Abraham's method. 4 rabbits are divided into the experimental group and control group. The biosecurity of SIS as scaf-folds were investigated in pyrogen test, skin sensitization test and systemic toxicity test. The SMSCs and SIS were co-cultured in vitro and induced to differentiate into cartilage to explore the biocompatibility of SMSCs and SIS, the proliferation and differ-entiation ability of SMSCs on the scaffold of SIS. The varietyies were identified by the microscope. Results The SIS isolated with the physical method and Abraham's method is a milky and translucent membrane with a smooth surface. Under the electron microscope, SIS presented a porous Stereoscopic three-dimensional network structure, which is formed by fibrous tissues' intertex-ture. Its' porosity was about 80%and its aperture was 100-200μm. Meanwhile, the biosecurity and biocompatibility of SIS were also fine. In the trial that the SMSCs and SIS were co-cultured in vitro, the SMSCs can grow, adhere to and differentiate on the sur-face of SIS and into the hollows very well. It can also secrete extracellular matrix. Through scanning microscope observation, cells contact with each other by their neuritis, or adhered to the wall of hole by cellular protrution. On the surface of SIS, the SMSCs maintain the property that it can easily differentiate into the chondrogenic lineage in the chondrogenic medium. Immunochemistry staining showed positive expression of type II collagen post 21 days of co-cultrue. Conclusion SIS can be used as the scaffold to construct tissue engineering meniscus as it has good biosecurity and biocompatibility with SMSCs without disturbing the cell form or inhibiting the growth and function of SMSCs.

Objective To investigate the effect of total knee arthroplasty ( TKA) following high tibial osteotomy ( HTO) and to analyze the factors that may influence the operation .Methods A total of 16 patients (19 knees) who had undergone a previous HTO were treated with TKA between 2000 and 2010.The American Knee Society Scores ( KSS), femorotibial angle ,quadriceps angle ,posterior slope angle of tibial plateau ,Insall Salvatti Ratio and knee range of motion ( ROM) were evaluated for each patient pre-and post-operatively and the results were evaluated .Results The KSS scores improved from 73.20 ±3.56 scores preoperatively to 153.00 ±3.39 scores postoperatively (P <0.05).The femorotibial angle was corrected from 160.57°±3.30°preoperatively to 169.85°±1.34°postoperatively(P<0.05).The quadriceps angle was corrected from 24.57°±2.07°preoperatively to 17.28°±1.11°postoperatively (P<0.05).The posterior slope angle of tibial plateau was corrected from 2.25°±0.50°preoperatively to 3.75°±0.95°postoperatively (P<0.05).The Insall Salvatti Ratio improved from 0.80 ±0.08 preoperatively to 1.05 ±0.12 postoperatively ( P <0.05).The knee ROM improved to 38.25°±8.88°postoperatively from 96.25°±4.34°preoperatively(P<0.05).Conclusion TKA following HTO demands adequate soft tissue balancing , good limb alignment and appropriate prosthesis .

Objective To investigate the feasibility of spatiotemporal image correlation(STIC)to assess left ventricular volume in normal fetuses.Methods The volume data acquisition of 162 normal fetuses ranging between 22 and 38 weeks of gestation was achieved by automatic sweep scan.The virtual organ computer-aided analysis(VOCAL Ⅱ)was then used to evaluate end-systolic and end-diastolic volumes of left ventricle and compared with that obtained by M-mode Teichholz formula and 2D biplane Simpson's method.Results Twenty-six fetuses with poor STIC image and 2 twin pregnancies were excluded,the study subjects consisted of 134 singleton fetuses.The highest concordance correlation(r =0.968,for EDV,r =0.956 for ESV;P =0.000)was noted between 2D biplane Simpson' s and STIC VOCAL Ⅱ values with a small bias(0.282 ml for EDV,0.117 ml for ESV).The Bland-Altman analysis showed that STIC VOCAL Ⅱ had the best agreement than M-mode Teichholz formula and 2D biplane Simpson's method.The result showed that there were significant difference between Mmode Teichholz formula and Simpson's method in EDV and ESV(P＜0.05).There were significant differences between M-mode Teichholz formula and STIC VOCAL Ⅱ(P＜0.05).There were no significant differences between STIC VOCAL Ⅱ and Simpson' s method in EDV and ESV.Conclusions There is a good agreement between left ventricular volumes measured either by STIC VOCAL Ⅱ or by 2D biplane Simpson's method.STIC is a novel technique that can be more accurate than conventional Methods in quantification of fetal left ventricular volumes.All the volume data acquisition is achieved by postprocessing facilities.STIC promises to become a new method for left ventricular volume quantification.