[Molecular studies on parental origin and cell stage of nondisjunction in sex chromosome aneuploidies].

To study the parental origin and cell stage of nondisjunction in sex chromosome aneuploidies. Retrospectiving and analyzing the results of 385 cases of SCA confirmed by QF-PCR and karyotype analysis in the prenatal diagnosis center of Guangzhou Women and Children Medical Center from January 2015 to December 2020. The types of samples and prenatal diagnosis indications were analyzed. The parental origin and cell stage of nondisjunction in sex chromosome aneuploidies analyzed by comparing the short tandem repeat (STR) peak patterns of samples from fetuses and maternal peripheral blood. The results show that (1) There were 324 cases of nonmosaic SCA, 113 cases (113/324, 34.9%) were 45, XO, 118 cases (118/324, 36.4%) were 47, XXY, 48 cases (48/324, 14.8%) were 47, XXX and 45 cases (45/324, 13.9%) were 47, XYY. 68 (45/324, 60.2%) cases of 45, X were detected in villus samples. The other SCA cases were mainly detected in amniotic fluid samples. There were 61 mosaic SCA samples, 58(58/61, 95.1%) of mosaic SCA samples were mosaic 45, X. (2) The top two indications of 45, X cases are increased nuchal translucency(53/113, 46.9%) and fetal cystic hygroma (41/113, 36.3%), while the most common indication of other types of SCA was high risk of NIPT(170/272, 62.5%). (3) Among 45, X cases, there were 88 cases (88/113, 77.9%) inherit their single X chromosome from their mother and 25 cases (25/119, 22.1%) from their father. In 47, XXY samples, 47 cases (47/118, 39.8%) of chromosome nondisjunction occurred in meiosis stage Ⅰ of oocytes, 51 cases (51/118, 43.2%) occurred in meiosis stage Ⅰ of spermatocytes, and 20 cases (20/118, 16.9%) occurred in meiosis stage Ⅱ of oocytes. Among 47, XXX samples, 29 cases (29/48, 60.4%) of X chromosome nondisjunction occurred in meiosis stage Ⅰof oocytes, 15 cases (15/48, 31.3%) occurred in meiosis stage Ⅱ of oocytes, and 4 cases (4/48, 8.3%) occurred in meiosis stage Ⅱ of spermatocytes. In summary, the cases of 45, X were mainly diagnosed by villous samples for abnormal ultrasound findings. The other cases of SCA were mainly diagnosed by amniocentesis samples for abnormal NIPT results. Different types of SCA, the origin and occurrence period of sex chromosome nondisjunction were different.

AXIN2 gene silencing reduces apoptosis through regulating mitochondria-associated apoptosis signaling pathway and enhances proliferation of ESCs by modulating Wnt/ß-catenin signaling pathway.

OBJECTIVE: Embryonic stem cells (ESCs) mainly originate from totipotent cells in early-stage of mammalian embryo and could proliferate in a manner of un-limitation. This study aimed to investigate roles of Axin2 in proliferation of ESCs and explore the associated mechanisms. MATERIALS AND METHODS: Axis inhibition protein 2 (AXIN2) over-expression (LV5-AXIN2) and AXIN2 RNA interfere (LV3-AXIN2-RNAi) vectors were structured and transfected into H9 cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) was used to evaluate cell proliferative activity. Flow cytometry analysis was employed to measure apoptosis of H9 cells. AXIN2, ß-catenin, transcription factor 4 (TCF4), c-myc, c-jun and Cyclin D mRNA levels and protein expressions were determined using quantitative real-time PCR (qRT-PCR) and Western blotting assay. RESULTS: LV5-AXIN2 and LV3-AXIN2-RNAi were successfully structured with higher transfecting efficacy. AXIN2 gene silencing remarkably increased proliferative activity and AXIN2 treatment significantly induced apoptosis of H9 cells, comparing with blank vector group (p<0.05). AXIN2 gene silencing significantly enhanced B-cell lymphoma-2 (Bcl-2) expression and remarkably inhibited cleaved caspase-3 expression comparing to that in blank vector group (p<0.05). AXIN2-RNAi treatment significantly enhanced and AXIN2 over-expression significantly reduced ß-catenin and TCF4 expression, comparing to that in blank vector group (p<0.05). AXIN2 gene silence activated down-stream molecules of Wnt/ß-catenin signaling pathway, including c-jun, c-myc, and Cyclin D1 (p<0.05). CONCLUSIONS: AXIN2 gene silencing reduced apoptosis by regulating mitochondria-associated apoptosis signaling pathway and enhanced proliferation by modulating molecules in Wnt/ß-catenin signaling pathway. Therefore, targeting of aberrant apoptosis and AXIN2 might be a novel clinical strategy to inhibit aging and enhance self-renewal of ESCs.

Aclidinium bromide inhibits human glioma cell proliferation, migration and invasion and promotes apoptosis via the PI3K/AKT signaling pathway.

This study investigates the anti-cancer potential of Aclidinium bromide (INN) in glioblastoma. Glioblastoma cell lines U251 and U87 were treated with INN and its effects on cell migration and invasion were assessed by transwell migration and invasion assays., The effects of INN on proliferation and apoptosis were detected by CCK-8 kit and flow cytometry, and Western blotting determined anti-apoptotic proteins and signaling pathway changes. The results show that INN effectively suppressed proliferation, migration and invasion and induced apoptosis in U251 and U87 cells, respectively. Furthermore, the expression levels of the Bcl-2 anti-apoptotic protein was significantly decreased while Bax and caspase-3 expression were both increased in glioblastoma cells (all, p<0.05). Moreover, INN inactivated the PI3K/AKT signaling pathway by down-regulating the level of p-AKT, p-mTOR, P70 and CyclinD1 (all, p<0.05). In conclusion, our data suggests that INN could provide novel anticancer therapy in the treatment of glioblastoma.

Study on the effects of parecoxib on hypothalamus orexin neuron of cerebral infarction rats.

OBJECTIVE: To explore the effect of parecoxib on cerebral infarction in rats and the regulatory mechanism on hypothalamus orexin neurons (orexin) and protein expression. MATERIALS AND METHODS: 60 SD male rats were randomly divided into sham operation group, model group and treatment group (20 rats in each group). Cerebral infarction model was established by modified Longa method. Rats in the treatment group were given parecoxib (2.5 mg kg-1) in tail by intravenous injection, while both the sham operation group and the model group were given the equal volume of sterile PBS solution in the tail vein. Continuous intervention of 72h was carried out in the three groups. Immunofluorescence staining and Western blot were used to detect the expression of orexin neurons and orexin protein in the hypothalamus of rats, respectively. RESULTS: Immunofluorescence staining showed that the number of orexin positive cells in the model group was significantly less than that in the sham-operated group (p < 0.01). After treatment intervention, the number of orexin positive cells in the hypothalamus was significantly increased compared to that in model group (p < 0.01). Western blot analysis showed that compared with sham operation group, the expression of orexin in the hypothalamus of model group was significantly decreased (p < 0.01), whereas the expression of orexin protein was significantly elevated after parecoxib intervention (p < 0.01). CONCLUSIONS: Parecoxib plays a therapeutic effect on cerebral infarction by up-regulating the orexin neuron.

Whole exome sequencing as a diagnostic adjunct to clinical testing in fetuses with structural abnormalities.

OBJECTIVES: To evaluate the diagnostic yield of prenatal whole exome sequencing (WES) for monogenic disorders in fetuses with structural malformations and normal results on cytogenetic testing, and to describe information on pathogenic variants that is provided by WES. METHODS: Karyotyping, chromosomal microarray analysis (CMA) and WES were performed sequentially on stored samples from a cohort of 3949 pregnancies with fetal structural abnormalities detected on ultrasound and/or magnetic resonance imaging, referred between January 2011 and December 2015. Diagnostic rates of the three techniques were investigated overall, for phenotypic subgroups and for proband-only vs fetus-mother-father samples. Information on pathogenic variants was identified by WES. RESULTS: Overall, 18.2% (720/3949) of fetuses had an abnormal karyotype. Pathogenic copy number variants were detected on CMA in 8.2% (138/1680) of fetuses that had a normal karyotype result. WES performed on a subgroup of 196 fetuses with normal CMA and karyotype results revealed the putative genetic variants responsible for the abnormal phenotypes in 47 cases (24%). The molecular diagnosis rates for fetus-mother-father and proband-only samples were 26.5% (13/49) and 23.1% (34/147), respectively. Variants of uncertain significance were detected in 12.8% (25/196) of fetuses, of which 22 were identified in the fetal proband-only group (15%; 22/147) and three in the fetus-mother-father group (6.1%; 3/49). The incidental finding rate was 6.1% (12/196). CONCLUSIONS: WES is a promising method for the identification of genetic variants that cause structural abnormalities in fetuses with normal results on karyotyping and CMA. This enhanced diagnostic yield has the potential to improve the clinical management of pregnancies and to inform better the reproductive decisions of affected families. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

[Clinical study of chondrosarcoma in the jugular foramen].

Objective:To explore the diagnosis and surgical treatment of chondrosarcoma in the jugular foramen (JF).Method:This study lies on the retrospective analysis about 72 patients with secondary hyperparathyroidism who had parathyroid gland resection in our hospital from 2010 to 2017. All of 72 cases are examined by color doppler ultrasound,99mTC-MIBI nuclide imaging and magnetic resonance imaging. According to the gold standard pathological diagnosis after surgery, we compute the sensitivity and the specificity of various imaging examination and analyse these statistics by rate card square test with SPSS 19.0 software.Result:The main complaints in the patients included hearing loss, facial palsy and tinnitus. All patients achieved total removal with IFTA-A as initial treatment. Three cases underwent facial nerve grafting and preoperative cranial nerve dysfunction didn't aggravate in our cases. No recurrence or major complication has been identified till the latest follow up.Conclusion:Chondrosarcoma in the JF is a rare entity. Misdiagnosis frequently occurs in clinical practice. Special attention should be paid to the clinical characteristics and radiological findings when encounters a lesion in the jugular foramen. It is believed that the complete resection of the tumor should be the initial choice for patients with chondrosarcoma in the JF.

[Expression of eosinophils and IL-33 levels in peripheral blood of patients with allergic rhinitis].

Objective:To investigate the relationship between the count of eosinophils(EOS) in peripheral blood and the serum levels of IL-33, and to discuss the relations among serum levels of IL-33, the count of EOS, visual analog scale (VAS) in different groups.Method:According to different treatments, the patients are divided into three groups: the untreated allergic rhinitis (AR) group (group A), the AR group who had been treated subcutaneous imunotherapy (SCIT) for at least a year (group B) and the AR complicated with allergic asthma group who had been treated subcutaneous imunotherapy (SCIT) for at least a year (gourp C). All subjects were conducted blood cell analysis, and EOS were counted. The serum levels of IL-33 were measured by enzyme linked immune (ELISA), and the obtained date were analysed by GraphPad.Prism 5.0 and SPSS 22.0.AR patients were asked to fill out VAS and were assessed nasal symptoms.Result:The serum levels of IL-33 in the group A were higher than that in other subjects (P<0.05).The serum levels of IL-33 in the group B showed no significant difference between the group B and the group C (P> 0.05).The serum levels of IL-33 in the group B were higher than that in the control group (P<0.05).The serum levels of IL-33 in the group C were higher than that in the control group (P<0.05).The count of EOS in the group A were higher than that in other subjects, and there is no difference between with each other (P> 0.05).The VAS in the group A were higher than that in the group B (P<0.05) and there is no significant difference between the group A and the group C (P<0.05).There is no difference between the group B and the group C(P<0.05).After at least one-year SCIT, the symptoms of AR patients were obviously relieved, such as consciously rhinobyon, rhinorrhea, sneezing and so on. Spearman test showed the serum levels of IL-33 in the AR patients has a weak correlation with the count of eosinophils (P> 0.05, r=0.287).Conclusion:SCIT is an effective treatment for AR patients. role on AR, which can alleviate the symptoms of patients, also can reduce the levels of IL-33 and the count of EOS in peripheral blood.

Chronic periodontitis and the risk of erectile dysfunction: a systematic review and meta-analysis.

The objective of this study is to evaluate the association between chronic periodontitis (CP) and the risk of erectile dysfunction (ED). Electronic search using PubMed, Embase and the Cochrane Library was carried out for observational studies, longitudinal, cohort, case-control and epidemiological studies on humans, published up to December 2015. Manual searches were also performed. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the association between CP and the risk of ED. Methodological quality assessment was carried out using the Newcastle-Ottawa Quality Assessment Scale. Four case-control studies and one cross-sectional studies involving 213, 006 participants were included. Based on the random-effects model, analyses of all studies showed that CP was associated with an increased risk of ED (OR=2.28, 95% CI: 1.50-3.48). There was heterogeneity among the studies (P<0.001, I2=97.8%). Estimates of total effects were generally consistent with the sensitivity and subgroup analyses. In conclusion, our meta-analysis suggested that there was a significant association between CP and the risk of ED. Further epidemiological studies are needed to better estimate the key risk factors for periodontitis and their interaction effects.

Vasectomy and risk of prostate cancer: a systematic review and meta-analysis of cohort studies.

The results of published literature focusing on the association between vasectomy and the incidence of prostate cancer are often inconsistent. We conducted a meta-analysis to provide a quantitative assessment of the association between vasectomy and the risk of prostate cancer. We identified all cohort studies by searching the PubMed, Embase, and Cochrane Library before August 2014. The quality of the studies was evaluated using the Newcastle-Ottawa Scale checklist. Summary effect estimates with 95% confidence intervals (CI) were derived using a fixed or random effects model, depending on the heterogeneity of the included studies. Nine cohort studies that spanned across two continents involving 1 127 096 participants (ages 20-75) with 7539 cases of prostate cancer cases were included in the meta-analysis. The overall combined relative risks for men with the reference group were 1.08 (95% CI: 0.87-1.34) in a random effects, however, the association was not statistically significant (p = 0.48). Estimates of total effects were generally consistent in the sensitivity and subgroup analyses. No evidence of publication bias was observed. This meta-analysis indicated that vasectomy may not contribute to the risk of prostate cancer. The conclusion might have a far-reaching significance for the public health, especially in countries with high prevalence rates of vasectomy.

Removal of titanium dioxide nanoparticles by coagulation: effects of coagulants, typical ions, alkalinity and natural organic matters.

To investigate the possibility of removing titanium dioxide nanoparticles (TiO2 NPs) from water by coagulation, as well as to find the optimal coagulant and experimental conditions for TiO2 NP removal, four types of coagulant were adopted: polyferric sulfate (PFS), ferric chloride (FeCl3), polyaluminum chloride (PACl), and alum (Al2(SO4)3). It was found that the removal of TiO2 NPs by coagulation was affected by ionic strength, alkalinity, as well as types and dosages of coagulants. PFS and FeCl3 achieved much higher removal efficiency of TiO2 NPs than PACl and Al2(SO4)3 did. For 30 mg/L TiO2 NPs, a dosage of 0.3 mM PFS (as Fe) achieved 84% removal after coagulation followed by 30 min settlement. Optimal ionic strength (0.1 M NaCl or 0.03 M CaCl2) is of vital importance for the performance of PFS. Na2SO4 is unfavorable for the performance of PFS. Optimal alkalinity (0.01-0.03 M NaHCO3) is necessary for FeCl3 to remove TiO2 NPs. Natural organic matter, as represented by humic acid (HA) up to 11 mg/L, reduces the removal of TiO2 NPs by coagulation. These findings indicate that coagulation is a good option for the removal of TiO2 NPs from water, and more attention should be paid to the effects of water quality when using coagulation to remove TiO2 NPs from aqueous matrices. This provides a possible solution to alleviate the potential hazard caused by TiO2 NPs.

Dispersion and stability of titanium dioxide nanoparticles in aqueous suspension: effects of ultrasonication and concentration.

The increasing applications of titanium dioxide (TiO(2)) nanoparticles raise concerns about their potential environmental impacts. To investigate the fate and transport of TiO(2) nanoparticles in aqueous suspension, ultrasonication is widely used for the dispersion of TiO(2) nanoparticles in laboratory-scale studies. There is a pressing need for detailed information on the dispersion and stability of TiO(2) nanoparticles. This study investigated the change of size, zeta potential, and pH of TiO(2) nanoparticles aqueous suspension under different conditions of ultrasonication and concentrations. It was found that the hydrodynamic diameter of TiO(2) nanoparticles decreased with increasing suspension concentration and remained stable for more than 1 hour after sonication, which is enough for experimental research. The pH decreased with increasing nanoparticles concentration. Ultrasonication remarkably improved zeta potential to be above 15 mV for all the samples. Therefore, 20 minutes of ultrasonication (180 W) is sufficient for the dispersion of this rutile TiO(2) nanoparticles suspension, which can remain stable for more than 1 hour. However, the optimum sonication time for TiO(2) nanoparticles dispersion is influenced by many factors, such as TiO(2) nanoparticles concentration, solution chemistry, and sonicator parameters.

Diastematomyelia: a retrospective review of 138 patients.

Diastematomyelia is a rare congenital abnormality of the spinal cord. This paper summarises more than 30 years' experience of treating this condition. Data were collected retrospectively on 138 patients with diastematomyelia (34 males, 104 females) who were treated at our hospital from May 1978 to April 2010. A total of 106 patients had double dural tubes (type 1 diastematomyelia), and 32 patients had single dural tubes (type 2 diastematomyelia). Radiographs, CT myelography, and MRI showed characteristic kyphoscoliosis, widening of the interpedicle distance, and bony, cartilaginous, and fibrous septum. The incidences of symptoms including characteristic changes of the dorsal skin, neurological disorders, and congenital spinal or foot deformity were significantly higher in type 1 than in type 2. Surgery is more effective for patients with type 1 diastematomyelia; patients without surgery showed no improvement.

Evaluation of performance of measurement of faecal α(1)-antitrypsin clearance and technetium-99m human serum albumin scintigraphy in protein-losing enteropathy.

BACKGROUND AND AIM: Our study aimed to compare the performance of faecal α(1)-antitrypsin clearance (AATC) and radiolabelled human serum albumin (HSA) scintigraphy in protein-losing enteropathy (PLE). METHODS: Patients studied by both AATC and technetium-99m ((99m)Tc)-labelled HSA scintigraphy were recruited and categorized into PLE and non-PLE groups based on clinical and laboratory findings. The performance of AATC and (99m)Tc-labelled HSA scintigraphy was evaluated using clinical diagnosis of PLE as a gold standard. RESULTS: 29 patients were recruited and 13 patients were considered to have definite PLE (PLE group). In the PLE group, all patients had a positive HSA scinigraphy and 10 (77%) had demonstrable positive tracing in the early phase. Conversely, only 6 of them (46%) had elevated AATC level (>13 m/day). Results of (99m)Tc-labelled HSA scan (but not AATC) showed significant agreement with the clinical diagnosis (κ 0.35, p = 0.013). (99m)Tc-labelled HSA scintigraphy carried higher sensitivity (100 vs. 46%) and negative predictive value (100 vs. 63%) compared to AATC in diagnosing PLE. The correlation between the results of these two investigations was only modest (κ 0.27, p = 0.04). The area under the receiver operating characteristic curve of AATC level showed no optimal diagnostic cut-off for PLE. CONCLUSION: (99m)Tc-labelled HSA scintigraphy was superior to AATC in diagnosing PLE.

Contribution of cell-surface components to Cu2+ adsorption by Pseudomonas putida 5-x.

The contribution of various cell-surface components to Cu2+ adsorption by a Gram-negative bacterium, Pseudomonas putida 5-x, that was isolated from local electroplating effluent with a high capability to accumulate heavy metal ions was studied. The cell superficial layer had a negative effect on Cu2+ adsorption of the bacterial cells. Cu2+ adsorption capacity of the separated cell envelopes was fivefold more than that of the intact cells, owing to the liberation of more and more binding sites during the separation process. Some main components in the cell envelope, such as the peptidoglycan (PEG) layer, outer membrane, and inner membrane, provide the capability for Cu2+ adsorption. The content of the components in the cell envelope is in the order inner membrane > outer membrane > PEG layer, and their Cu2+ adsorption capacity was in the order PEG layer > outer membrane > inner membrane. The total contribution of the separated PEG layer material to Cu2+ adsorption by the cell envelope was no more than 15%, and the outer membrane and inner membrane contributed about 30-35% and 25-30%, respectively. The relatively high phospholipid content in the outer membrane may be the major reason for the higher adsorption capacity of the outer membrane to Cu2+ and, hence, such a high Cu2+ adsorption capacity of P. putida 5-x cell envelope.

Systematic review of radiological imaging for hepatocellular carcinoma in cirrhotic patients.

We systematically reviewed the evidence for determining the best radiological imaging for characterizing hepatocellular carcinoma (HCC) in cirrhotic patients in 997 articles between 1995 and 2001. We selected only prospective and retrospective cohorts of patients, excluding both case reports and studies without separate data on HCC. Only 29 studies, comprising 918 patients, fulfilled the inclusion criteria: 10 used the explanted liver as the reference standard of diagnosis. All except one, either found no statistically significant difference between imaging modalities or had no direct comparison of sensitivity between different modalities of imaging; 16 studies evaluated HCC among cirrhotic patients and had biopsy or imaging as the reference standard for diagnosis. However, no one imaging technique was shown to be superior. In two studies, data of a HCC subgroup was derived from the studies evaluating different kinds of focal hepatic lesions. No conclusion could be drawn because of the small sample size. One study addressed the issue of therapeutic impact. The evidence for choosing the best modality of imaging for characterizing HCC in cirrhotic patients is inadequate. Large multicentre studies with defined reference standards for diagnosis, and studies evaluating therapeutic impact are needed.

Relapses in leprosy patients treated with rifampicin plus dapsone after varying periods of dapsone monotherapy.

Leprosy patients treated formerly with dapsone monotherapy followed by combined therapy with rifampicin plus dapsone were surveyed for relapse and rifampicin resistance. The relapse rate was significantly low for the 482 multibacillary (MB) patients receiving > 12 months combined therapy compared with the 49 MB cases receiving < 12 months of combined therapy. The relapse rate was related to the duration of dapsone monotherapy prior to combined therapy. The difference in relapse rate in 247 paucibacillary (PB) patients following > 12 months combined therapy was also of significance, compared with the 66 PB cases who had received < 12 months combined therapy. Five strains of M. leprae isolated from relapsed patients were sensitive to rifampicin by mouse foot-pad test and all relapsed patients responded favourably to fixed duration MDT regimen for MB cases.

[Detection of serum antibody against lipoarabinomannan-B in Mycobacterium tuberculosis (H37Ra)].

The serum antibody to lipoarabinomannan-B(LAM-B) purified from mycobacterium tuberculosis (H37Ra) was tested by ELISA in 250 sera, including sera from patients as follows: tuberculosis 96, tubercular pleurisy 11, renal tuberculosis 2, bone and joint tuberculosis 33, tubercular meningitis 16, pulmonary cancer 22, leprosy 20 and normal subjects 50. The positive rate of pulmonary tuberculosis is 69.8%, which is of a similar extent in sera from patients with tuberculosis of miscellaneous organs to be tested except tubercular meningitis, in which only 18.8% positive rate was observed, indicating the blockage of antibody releasing from pathologic foci into blood stream by blood-brain barrier. The positive rates of leprosy and normal subjects are 50.0% and 2.0% respectively. No antibody was found among 22 patients with pulmonary cancer. It is suggested that the existence of an active tubercular lesion in the host might be the basic prerequisite for a positive LAM-B antibody detection. Although LAM-B is a common antigen of both mycobacterium tuberculosis and mycobacterium leprae, the low prevalence of leprosy in China makes little influence of the practicability of using this ELISA in epidemiological study and in clinic as a adjutant tool for tuberculosis diagnosis and differential diagnosis.