[Analysis on tissue-related biomarkers in patients with acute aortic dissection].

Objective: To explore the clinical implication of tissue-related biomarkers in patients with acute aortic dissection (AAD). Methods: It was a cross-sectional study. Ten Stanford Type A AAD patients, who were diagnosed and surgically treated in the Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, from December 2018 to August 2019, were selected as the case group. Meanwhile, 10 patients with atherosclerotic heart disease, who underwent coronary artery bypass grafting (CABG), were selected as control group. The ascending aorta tissue specimens from patients of the two groups were collected during the operation. Four-dimensional non-standard quantitative proteomics technology (4D-LFQ) was used to detect the protein profile of ascending aorta tissue specimens of the two groups and to screen out differentially expressed proteins and analyze their biological functions. Precise quantification of the selected target proteins was achieved by parallel response monitoring (PRM). Results: A total of 3 985 proteins were identified by 4D-LFQ technology, among which 3 350 proteins could be quantified. There were 39 proteins were significantly upregulated and 47 proteins were significantly downregulated in AAD group. The results of biological function analysis showed that most of the differentially expressed proteins were located in the extracellular, and their functions were mainly involved in cell migration and proliferation, inflammatory cell activation, cell contraction, and muscle organ development. The 15 selected proteins underwent precise quantification by PRM, and the results showed that integrin α-Ⅱb (ITGA2B), integrin α-M (ITGAM), integrin ß-2 (ITGB2), integrin ß-3 (ITGB3) were significantly upregulated in the ascending aorta tissue of AAD patients. Conclusion: ITGA2B, ITGAM, ITGB2, and ITGB3 are highly expressed in aortic tissues of patients with AAD, which may be used as biomarkers for the diagnosis of AAD patients.

Behavioral and Structural Effects of Single and Repeat Closed-Head Injury.

BACKGROUND AND PURPOSE: The effects of multiple head impacts, even without detectable primary injury, on subsequent behavioral impairment and structural abnormality is yet well explored. Our aim was to uncover the dynamic changes and long-term effects of single and repetitive head injury without focal contusion on tissue microstructure and macrostructure. MATERIALS AND METHODS: We introduced a repetitive closed-head injury rodent model (n = 70) without parenchymal lesions. We performed a longitudinal MR imaging study during a 50-day study period (T2-weighted imaging, susceptibility-weighted imaging, and diffusion tensor imaging) as well as sequential behavioral assessment. Immunohistochemical staining for astrogliosis was examined in a subgroup of animals. Paired and independent t tests were used to evaluate the outcome change after injury and the cumulative effects of impact load, respectively. RESULTS: There was no gross morphologic evidence for head injury such as skull fracture, contusion, or hemorrhage on micro-CT and MR imaging. A significant decrease of white matter fractional anisotropy from day 21 on and an increase of gray matter fractional anisotropy from day 35 on were observed. Smaller mean cortical volume in the double-injury group was shown at day 50 compared with sham and single injury (P < .05). Behavioral deficits (P < .05) in neurologic outcome, balance, and locomotor activity were also aggravated after double injury. Histologic analysis showed astrogliosis 24 hours after injury, which persisted throughout the study period. CONCLUSIONS: There are measurable and dynamic changes in microstructure, cortical volume, behavior, and histopathology after both single and double injury, with more severe effects seen after double injury. This work bridges cross-sectional evidence from human subject and pathologic studies using animal models with a multi-time point, longitudinal research paradigm.

A novel flow sensor based on resonant sensing with two-stage microleverage mechanism.

The design, simulation, fabrication, and experiments of a novel flow sensor based on resonant sensing with a two-stage microleverage mechanism are presented in this paper. Different from the conventional detection methods for flow sensors, two differential resonators are adopted to implement air flow rate transformation through two-stage leverage magnification. The proposed flow sensor has a high sensitivity since the adopted two-stage microleverage mechanism possesses a higher amplification factor than a single-stage microleverage mechanism. The modal distribution and geometric dimension of the two-stage leverage mechanism and hair are analyzed and optimized by Ansys simulation. A digital closed-loop driving technique with a phase frequency detector-based coordinate rotation digital computer algorithm is implemented for the detection and locking of resonance frequency. The sensor fabricated by the standard deep dry silicon on a glass process has a device dimension of 5100 µm (length) × 5100 µm (width) × 100 µm (height) with a hair diameter of 1000 µm. The preliminary experimental results demonstrate that the maximal mechanical sensitivity of the flow sensor is approximately 7.41 Hz/(m/s)2 at a resonant frequency of 22 kHz for the hair height of 9 mm and increases by 2.42 times as hair height extends from 3 mm to 9 mm. Simultaneously, a detection-limit of 3.23 mm/s air flow amplitude at 60 Hz is confirmed. The proposed flow sensor has great application prospects in the micro-autonomous system and technology, self-stabilizing micro-air vehicles, and environmental monitoring.

A comparison of clinical efficacy and economic value in Basalin- and Lantus-treated patients with type 2 diabetes using continuous glucose monitoring system.

AIM: To determine the clinical non-inferiority of recombinant glargine-Basalin vs glargine-Lantus, in treatment of type 2 diabetes mellitus (T2DM) using continuous glucose monitoring system (CGMS). METHODS: One hundred patients with T2DM were recruited. They were either regularly taking Basalin (Basalin group) or Lantus (Lantus group) (n = 50 each). CGMS was employed to real-time monitor blood glucose profile for 4 days (from day 1 to day 5). To exclude the effect of patient background, the study design was to have a blinded crossover from glargine-Basalin to glargine-Lantus on day 3, and vice versa. 24-hour mean blood glucose (24hMBG), 24-hour standard deviation of blood glucose (24hSDBG), 24-hour mean amplitude of glycemic excursion (24hMAGE), and number of glycemic excursion (NGE) every 24 h (24hNGE) were calculated for each glargine from 100 patients. RESULTS: No significant difference of 24hMBG, 24hSDBG, 24hMAGE, and 24hNGE (p > 0.05 for all) was found between Basalin and Lantus treatments. The glucose area under the curve and time when blood glucose was below 3.9 mmol/L, between 3.9 and 10.0 mmol/L, or above 10.0 mmol/L were similar between Basalin and Lantus treatment. The frequency of hypoglycemic episodes was also similar. However, the mean cost of Basalin was only 72% of Lantus's in one treatment course. CONCLUSION: Glargine-Basalin is non-inferior in clinical efficacy compared to glargine-Lantus. In view of the large difference in the cost of glargine-Basalin, it would be much more cost-effective for our patients.

Time-lapse observation and transcriptome analysis of a case with repeated multiple pronuclei after IVF/ICSI.

PURPOSE: The purpose of this study was to investigate the cause of repeated multipronucleus (MPN) formation in zygotes in a patient after both in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). METHOD: This is a case study. A patient had unexplained primary infertility with recurring total MPN zygotes after IVF and ICSI cycles. Time-lapse monitoring of pronucleus formation was carried out. Embryos developed from MPN zygotes were analyzed by fluorescence in situ hybridization (FISH). Single-cell RNA-seq analysis was used to identify gene expression profiles of the patient's oocyte and zygote, and these were compared to the data from oocytes and zygotes from donors with normal fertilization (patient, n = 1; donors, n = 4). Oocyte-specific genes with differential expression were selected by the Amazonia! RESULTS: From time-lapse analysis, we observed the formation of multiple micronuclei near the site of the second polar body extrusion. These micronuclei migrated, expanded, and juxtaposed with the male pronucleus leading to a multipronucleus. None of these MPN zygotes could develop to the blastocyst stage, and FISH analysis revealed a chaotic chromosomal complement in the arrested embryos. RNA-seq analysis showed 113 differentially expressed genes (DEGs) between the patient and the donor oocytes and zygotes. Moreover, 25 of the 113 DEGs were unique or highly expressed in oocytes and early embryos. From 25 DEGs, three genes, DYNC2LI1, NEK2, and CCNH, which are involved in meiosis and the chromosome separation process, were further validated by real-time PCR. CONCLUSION: We identified several candidate genes affecting pronucleus formation as a new cause of infertility.

Cleavage pattern predicts developmental potential of day 3 human embryos produced by IVF.

Time-lapse technique provides opportunities to observe the dynamic process of human early development. Previous studies have suggested several abnormal division patterns were associated with decreased developmental potential, but no systematic results are currently available. In this study, seven abnormal division patterns were observed during early cleavage, and these had different effects on the further development potential of daughter blastomeres. According to the severity and occurrence of abnormal division patterns during the initial three cleavages, an embryo hierarchical classification model was developed and day 3 embryos were classified into six grades (from A to F). The good-quality blastocyst formation rate for these grades decreased from 70.8-3.8% (P < 0.001). In a prospective observational study, 139 IVF cycles were recruited to assess the efficiency of this classification model. In the embryos that had confirmed implantation results, the implantation rate decreased from 67.0% (Grade A) to 0% (Grade D;P < 0.001). These results indicated that cleavage patterns can predict the developmental potential of day 3 human embryos.

Using SNP array to identify aneuploidy and segmental imbalance in translocation carriers.

Translocation is one of the more common structural rearrangements of chromosomes, with a prevalence of 0.2%. The two most common types of chromosomal translocations, Robertsonian and reciprocal, usually result in no obvious phenotypic abnormalities when balanced. However, these are still associated with reproductive risks, such as infertility, spontaneous abortion and the delivery of babies with mental retardation or developmental delay. In recent years, array-based whole-genome amplification (WGA) technologies, including microarray comparative genomic hybridization (array CGH; aCGH) and single-nucleotide polymorphism (SNP) micro-arrays, have enabled the screening of every chromosome for whole-chromosome aneuploidy and segmental imbalance. These techniques have been shown to have clinical application for translocation carriers. Promising studies have indicated that array-based PGD of translocation carriers can lead to transfer pregnancy rates of 45-70% [2]. In addition to genetic testing techniques, the embryo biopsy stage (polar body, cleavage embryo or blastocyst) and the mode of embryo transfer (fresh or frozen embryos) can affect the outcome of PGD. It is now generally recommended that blastomere biopsy should be replaced by blastocyst biopsy to avoid a high mosaic rate and biopsy-related damage to cleavage-stage embryos, which might affect embryo development. However, more clinical data are required to confirm that the technique of SNP array-based PGD (SNP-PGD) combined with trophectoderm (TE) biopsy and frozen embryo transfer (FET) is superior to traditional FISH-PGD combined with Day 3 (D3) blastomere biopsy and fresh embryo transfer.

Single-nucleotide polymorphism microarray-based preimplantation genetic diagnosis is likely to improve the clinical outcome for translocation carriers.

STUDY QUESTION: Is preimplantation genetic diagnosis (PGD) for translocation carriers more effective when done with a single-nucleotide polymorphism (SNP) array using trophectoderm (TE) biopsy and frozen embryo transfer (FET) compared with traditional PGD based on fluorescence in situ hybridization (FISH-PGD) using blastomere biopsy and fresh embryo transfer? SUMMARY ANSWER: The procedure using the SNP array combined with TE biopsy and FET significantly improves the clinical pregnancy rate for translocation carriers. The miscarriage rate also slightly decreases. WHAT IS KNOWN ALREADY: FISH-PGD has been widely used in translocation carriers but the clinical outcomes have not been ideal. SNP arrays can detect both chromosome segmental imbalances and aneuploidy, and may overcome the limitations of FISH in PGD for translocation carriers. STUDY DESIGN, SIZE AND DURATION: This was a retrospective study of 575 couples with chromosomal translocations, including 169 couples treated by SNP-PGD between October 2011 and August 2012, and 406 couples treated by FISH-PGD between January 2005 and October 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was set in an IVF center at the Reproductive and Genetic Hospital of CITIC-Xiangya, China. In total, 169 couples underwent SNP analysis, including 52 Robertsonian translocation carriers and 117 carriers of reciprocal translocations. Blastocysts (n = 773) were biopsied and FET was carried out on the balanced embryos. Four hundred and six couples underwent FISH-PGD, including 149 Robertsonian translocation carriers and 257 reciprocal translocation carriers. In total, 3968 embryos were biopsied and balanced embryos were transferred fresh. The SNP-PGD results and clinical outcomes were compared with those of FISH-PGD. MAIN RESULTS AND THE ROLE OF CHANCE: Reliable SNP-PGD results were obtained for 717 out of 773 (92.8%) biopsied blastocysts. The proportions of normal/balanced embryos, embryos with translocation-related and translocation-unrelated abnormalities, the median number of embryos per patient, the ongoing pregnancy rate per embryo transfer and the miscarriage rate were 58, 23, 19, 2, 69 and 12%, respectively, for Robertsonian translocation carriers and 36, 52, 12, 1, 74 and 11%, respectively, in reciprocal translocation carriers. Reliable FISH-PGD results were obtained for 3452 out of 3968 (87.0%) biopsied embryos. The proportions of normal/balanced embryos, unbalanced embryos, the median number of embryos per patient, the ongoing pregnancy rate per transfer and the miscarriage were 36, 64, 3, 38 and 17%, respectively, for Robertsonian translocation carriers and 20, 80, 1, 39 and 16%, respectively, for reciprocal translocation carriers. Thus, SNP-PGD achieved a higher pregnancy rate but a lower miscarriage rate than FISH-PGD. There were no significant differences in maternal age, basal endocrine level and the average number of retrieved oocytes and good-quality D3 embryos in the SNP-PGD group compared with the FISH-PGD group. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study with the two groups treated in different periods; therefore, there is a chance of sample bias and a possibility that the results were influenced by other factors that changed over time. Furthermore, the two treatment protocols differ in several respects and we cannot say which makes the greatest contribution to the difference in success. Complete pregnancy outcomes of SNP-PGD have not been obtained as some embryos have not been transferred yet. We cannot exclude differences between the final data and the data in the present manuscript. WIDER IMPLICATIONS OF THE FINDINGS: The adoption of SNP-PGD combined with TE biopsy and FET may significantly improve the clinical pregnancy rate, and decrease the miscarriage rate after PGD for translocation carriers.

Paxillus involutus mycorrhiza attenuate NaCl-stress responses in the salt-sensitive hybrid poplar Populusxcanescens.

In order to characterise the effect of ectomycorrhiza on Na+-responses of the salt-sensitive poplar hybrid Populus x canescens, growth and stress responses of Paxillus involutus (strain MAJ) were tested in liquid cultures in the presence of 20 to 500 mM NaCl, and the effects of mycorrhization on mineral nutrient accumulation and oxidative stress were characterised in mycorrhizal and non-mycorrhizal poplar seedlings exposed to 150 mM NaCl. Paxillus involutus was salt tolerant, showing biomass increases in media containing up to 500 mM NaCl after 4 weeks growth. Mycorrhizal mantle formation on poplar roots was not affected by 150 mM NaCl. Whole plant performance was positively affected by the fungus because total biomass was greater and leaves accumulated less Na+ than non-mycorrhizal plants. Energy dispersive X-ray microanalysis using transmission electron microscopy analysis of the influence of mycorrhization on the subcellular localisation of Na+ and Cl- in roots showed that the hyphal mantle did not diminish salt accumulation in root cell walls, indicating that mycorrhization did not provide a physical barrier against excess salinity. In the absence of salt stress, mycorrhizal poplar roots contained higher Na+ and Cl- concentrations than non-mycorrhizal poplar roots. Paxillus involutus hyphae produced H2O2 in the mantle but not in the Hartig net or in pure culture. Salt exposure resulted in H2O2 formation in cortical cells of both non-mycorrhizal and mycorrhizal poplar and stimulated peroxidase but not superoxide dismutase activities. This shows that mature ectomycorrhiza was unable to suppress salt-induced oxidative stress. Element analyses suggest that improved performance of mycorrhizal poplar under salt stress may result from diminished xylem loading of Na+ and increased supply with K+.

Preserving pulpal health of a geminated maxillary lateral incisor through multidisciplinary care.

AIM: To report the multidisciplinary care of an unaesthetic geminated maxillary lateral incisor tooth, which allowed its preservation in the mouth. SUMMARY: Preoperative examination of an unsightly geminated maxillary lateral incisor (tooth 22) demonstrated two pulp chambers and open apices, with normal pulp sensitivity responses. At surgery, a periodontal mucoperiosteal flap was reflected and the distal part of the geminated tooth was removed. The exposed root canal of the preserved tooth was sealed with mineral trioxide aggregate (MTA). The extraction socket and osseous defect was grafted with decalcified freeze-dried bone allograft (DFDBA) before flap closure. During follow-up, distal caries in tooth 22 and a diastema between tooth 22 and 23 were managed with composite resin restorations. Forty-two months postoperatively, normal thermal and electrical pulp sensitivity tests confirmed pulp health. Convincing apexogenesis and dentinogenesis of the developing root was confirmed by radiographic examination. Acceptable periodontal health including 3-4 mm clinical probing depths was achieved. Optimizing aesthetics and occlusion was accomplished without orthodontic treatment.

Measles seroepidemiology and decay rate of vaccine-induced measles IgG titers in Taiwan, 1995-1997.

Community-based seroepidemiologic studies were conducted to monitor the effectiveness of measles immunization programmes and to estimate the decay rate of vaccine-induced measles IgG titres. Sera collected from a mountain (792 sera), rural (875 sera) and urban (894 sera) populations in 1995-1997 were available. Measles IgG was quantified using a commercial EIA kit. Measles IgG seroprevalence and geometric mean titre (GMT) were calculated by setting the cut-off titre at 50 mIU/ml. The decay rate of measles IgG titres was estimated by assuming that the measles IgG titres, without exposing to wild measles virus, decay exponentially and constantly after 1 year post vaccination. The half-life of measles IgG titres was calculated from the corresponding decay rate. Measles IgG seroprevalences in these three populations have reached >95% in school children (7-18 years old) and >98% in young adults (19-25 years old) but varied from 87 to 96% in pre-school children (4-6 years old). Two-dose vaccinees, comparing with 1-dose vaccinees, had a significantly higher seroprevalence (98 versus 92%, P<0.01) and a slightly longer half-life of measles IgG titres (61 versus 27 months, P=0.08) but the measles IgG GMT in the two groups did not differ significantly (675 versus 618 mIU/ml, P=0.78).

Persistent hyperendemicity of hepatitis C virus infection in Taiwan: the important role of iatrogenic risk factors.

The purpose of this study was to investigate determinants of endemic hepatitis C virus (HCV) infection within communities in Taiwan. A two-phase study, including a seroprevalence survey and a prevalent case-control study at the first phase, which has been published previously, and a follow-up seroconversion determination and an incident case-control study during the second phase, was carried out to evaluate correlates of persistent endemic HCV infection. At the first phase, a total of 12,021 men and 1,819 women who were 30-64 years old and living in seven townships in Taiwan were tested for the seroprevalence of antibodies to HCV (anti-HCV). In addition, a prevalent case-control study involving 272 HCV-positive cases and 282 seronegative controls identified from the anti-HCV testing was conducted to investigate risk factors associated with HCV prevalence. During the second phase, a total of 2,728 men and 834 women who were seronegative at recruitment participated in the 1-year prospective study on anti-HCV seroconversion. Subsequently, an incident case-control study based on 39 seroconverters and 81 persistently seronegative controls were carried out to elucidate determinants of HCV seroconvertion. Antibodies to HCV were tested by the second-generation enzyme immunoassay. Information on risk factors of HCV infection was collected from subject interviews. The prevalence of anti-HCV consistently increased with age (range 2.9-5.4%), whereas no apparent age trend was observed for anti-HCV seroconversion rate (range 0.9-1.7%). A striking geographical variation in seroprevalence and seroconversion rates of anti-HCV was observed in the study townships. Furthermore, a significant geographical correlation between HCV seroprevalence and seroconversion rates was noted (r = 0.962, P = 0.001). From the results of both prevalent and incident case-control comparisons, medical injections were found to be the main mode to sustain the persistent endemic state of HCV infection within a community (odds ratios for prevalent and incident case-control studies were 2.5 (95% CI = 1.7-3.6) and 3.1 (95% CI = 1.4-7.1), respectively. The data indicate that the basis for HCV transmission has already been existed in study areas and the iatrogenic risk factor tended to be the major determinant for sustaining persistent endemicity within a community.

Risk factors associated with hepatitis C virus infection in Taiwanese government employees.

This study evaluated the roles of multiple factors in hepatitis C virus (HCV) infection, with emphasis on the modification of various individual characteristics on the risk associated with percutaneous exposure to blood. Serum samples taken from 4869 men in Taiwan within a cohort study were tested for HCV antibody. The overall positive rate of anti-HCV was 1.6%. In a logistic regression, factors positively associated with anti-HCV positivity were previous blood transfusion (odds ratio [OR] = 7.28: 95% confidence interval [CI] = 4.26-12.45), a history of surgery (OR = 2.06: 95% CI = 1 23-3.46), and lower educational levels (OR = 1.94; 95% CI = 1.14-3.32). The anti-HCV positive rate was significantly lower in hepatitis B surface antigen (HBsAg) carriers than in non-carriers (OR = 0.60; 95% CI = 0.37-0.95). Ageing, lower educational levels, O blood group, and Taiwanese ethnicity enhanced the likelihood of HCV infection through blood transfusion/surgery, whereasHBsAg status, cigarette smoking, and habitual alcohol drinking reduced it.

[Retrospective analysis of 102 cycles of intracytoplasmic single sperm injection in treating severe male infertility and fertilization failure].

The aim of this study is to retrospectively analyze 102 cycles which received intracytoplasmic single sperm injection (ICSI) in our lab from January 1998 to December 2000. With the improvements of the technique and environment of the microscopic manipulation from February 2000, the survival rate (90.6%). fertilization rate (73.3%) and embryo development rate (97.3%) of the later stage were significantly higher than those of the previous (68.8%, 39.0%, 78.7% respectively). The clinical pregnancy rate reached a higher level (41.3% and 21.4% respectively). The ICSI technique established currently in our lab can effectively treat the severe male infertility and fertilization failure.

Protective titres of measles neutralising antibody.

A nation-wide measles outbreak occurred in 1988 in Taiwan. A retrospective cohort study was conducted to define the protective titre of measles neutralising (NT) antibody. Paired sera collected in 1987 and 1988 were available from 190 individuals born in 1984 who had participated in an annual hepatitis B immunisation follow-up from 1986 to 1991. Measles NT titres were quantified using a standardised neutralisation enzyme immunoassay. Measles infection was defined as a >/=4-fold rise in NT titre or seroconversion between paired sera. Symptomatic measles infection was ascribed to individuals who had measles infection and who reported measles-like symptoms between 1987 and 1988. Results demonstrated a dose-response relationship between pre-exposure NT titres and protection against measles infection. 47 of 48 individuals with measles infection in 1988 had pre-exposure NT titres 1, 000 mIU/ml may prevent measles infection and NT titres >500 mIU/ml may prevent symptomatic infection but vaccinees with undetectable or low NT titres may not necessarily be susceptible to symptomatic infection.