[Whole exome sequencing analysis and prenatal diagnosis in children with neurodevelopmental disorders].

To explore the application value of whole exome sequencing (WES) in the diagnosis of prenatal and postnatal neurodevelopmental disorders (NDDs). A total of 70 patients diagnosed with NDDs who underwent WES at the Medical Genetics Center of the Maternal and Child Health Hospital of Hubei Province between June 2020 and July 2021 were retrospectively analyzed. Genomic DNA was extracted from peripheral blood samples and amniotic fluid. WES-based copy number variant (CNV) analysis was integrated into the routine WES data analysis pipeline. The results showed that a molecular diagnosis rate could be made in 21/70 (30%) cases. Of 21 positive cases, 14 (23%) cases were detected by single-nucleotide variant/small insertion/deletion (SNV/Indel) analysis, of which 12 variants were novel, 6 (9.8%) cases were detected by WES-based CNV analysis, and 1 (1.6%) case was detected by a combination of both. The diagnostic yield of WES combined with CNV analysis was higher than that of SNV/Indel analysis alone (30%, 21/70 vs. 20%, 14/70). Of the 28 prenatally diagnosed cases, 6 cases were found to have inherited parental variation for NDDs, 10 cases were found not to have the same pathogenic variation as the proband, and the remaining 12 cases were found to have no pathogenic or likely pathogenic variation that could explain the NDDs phenotype. Clinical follow-up showed that 5 families opted for abortion and the remaining had no current abnormalities. In conclusion, WES may be an effective method to clarify the genetic etiology and prenatal diagnosis of NDDs, which is helpful in assessing the prognosis to aid clinical management and reproductive guidance.

Effects of Selenium Supplementation on the Ion Homeostasis in the Reproductive Organs and Eggs of Laying Hens Fed With the Diet Contaminated With Cadmium, Lead, Mercury, and Chromium.

The objective of this study was to explore the toxic effects of different heavy metals in combination with their deposition and ion homeostasis in the reproductive organs and eggs of laying hens, as well as the alleviating action of selenized yeast. A total of 160 Lohmann pink-shell laying hens (63-week-old) were randomly allocated into four treatments with 10 replicates of four hens each. The four dietary treatments were the corn-soybean meal basal dietary (control; CON); the CON dietary supplemented with 0.4 mg/kg selenium from selenized yeast (Se); the CON dietary supplemented with 5 mg/kg Cd + 50 mg/kg Pb +3 mg/kg Hg + 5 mg/kg Cr (HEM), and the HEM dietary supplemented with 0.4 mg/kg selenium from selenized yeast (HEM+Se). The dietary HEM significantly increased Cd, Pb, and Hg deposition in the egg yolk and ovary, and Cd and Hg deposition in the oviduct and in the follicular wall (p < 0.05). The HEM elevated Fe concentration in the egg yolk, ovary, and oviduct (p < 0.05). The HEM decreased Mn concentration in the egg yolk, Fe, Mn, and Zn concentrations in the egg white, Cu concentration in the ovary, Mg concentration in the oviduct, as well as Ca, Cu, Zn, and Mg concentrations in the follicular walls (p < 0.05). Dietary Se addition elevated Se concentration in the egg yolk, oviduct, and follicular walls and Mg concentration (p < 0.05) in the oviduct, whereas it reduced Fe concentration in the oviduct compared with the HEM-treated hens. Some positive or negative correlations among these elements were observed. Canonical Correlation Analysis showed that the concentrations of Pb and Hg in the egg yolk were positively correlated with those in the ovary. The concentration of Cd in the egg white was positively correlated with that in the oviduct. In summary, dietary Cd, Pb, Hg, and Cr in combination caused ion loss and deposition of HEM in reproductive organs of laying hens. Dietary Se addition at 0.4 mg/kg from selenized yeast alleviated the negative effects of HEM on Fe and Mg ion disorder in the oviduct and follicle wall of hens.

[The application of hybrid operation suite in the management of cerebral and spinal vascular diseases and intracranial hypervascular tumors].

Objective: To evaluate the effect of hybrid operation suite in the treatment of cerebral and spinal vascular diseases and intracranial hypervascular tumors. Methods: A retrospective study was conducted on 132 patients with various cerebral and spinal vascular diseases and intracranial hypervascular tumors who were treated by hybrid surgery at Department of Neurosurgery, Huashan Hospital from October 2016 to December 2017.There were 70 male and 62 female patients with a mean age of 48.33 years (range: 14-78 years), including 64 cases of intracranial aneurysm (41 complicated aneurysm cases), 28 cases of brain arteriovenous malformation (BAVM), 12 cases of hypervascular tumor, 12 cases of dural arteriovenous fistula (DAVF), 6 cases of carotid artery stenosis, 5 cases of Moyamoya disease, 3 cases of intracranial aneurysm or BAVM combined with tumor, 1 case of scalp arteriovenous fistula and 1 case of critical brain trauma in which a foreign metal stick approached the basal vascular circuit.Abnormalities were found in 16 cases in intraoperative angiography. The clinical data of all patients was collected as a perspective cohort. The success rate of hybrid surgery, intra-operative and post-operative complications, morbidity, mortality, rate of infection, the length of hospital stay were all analyzed to illustrate the effect of hybrid operation mode to traditional surgical pattern. Results: For 64 cases with intracranial aneurysms, the immediate complete occlusion rate was 90.5%, with a mortality of 4.7% and a morbidity of 14.0%. For 28 cases of BAVM and 12 cases of DAVF, all patients achieved total obliteration and favorable social independent outcomes after hybrid surgery, with no complication.For 6 cases of carotid artery stenosis and 5 cases of Moyamoya, intra-operative confirmed good cerebral reperfusion without any new post-operative neurologic deficits. After tumor vessels embolization, 4 out of 12 cases of hypervascular tumor needed intra-operative blood transfusion, and all patients achieved total tumor resection in a single stage. Only one patient with medulla oblongata hemangioblastoma died 6 months after operation due to respiratory deficit related pneumonia. Compared to traditional surgeries, the hybrid operation pattern did not significantly increase the total infection rate, central nervous system infection rate, hospital stay days and post-operative hospital stay days (all P>0.05) while the in-patient cost increased mildly (119 332 yuan vs.98 215 yuan, t=2.38, P=0.02). Conclusions: The operations of complex cerebral and spinal vascular diseases and intracranial hypervascular tumors can be performed in hybrid operation suite safely.This surgical mode can ensure the quality of operation and promote the development of innovative and complicated surgical procedures.

The role of copper in the thermal conductivity of thermoelectric oxychalcogenides: do lone pairs matter?

Understanding the underlying mechanisms that suppress thermal conduction in solids is of paramount importance for the targeted design of materials for thermal management and thermoelectric energy conversion applications. Bismuth copper oxychalcogenides, BiOCuQ (Q = Se, Te), are highly crystalline thermoelectric materials with an unusually low lattice thermal conductivity of ∼0.5 Wm(-1) K(-1), a value normally found in amorphous materials. Here we unveil the origin of the unusual thermal transport properties of these phases. First principles calculations of the vibrational properties combined with analysis of in-situ neutron diffraction data, demonstrate that weak bonding of copper atoms within the structure leads to an unexpected vibrational mode at low frequencies, which is likely to be a major contributor to the low thermal conductivity of these materials. In addition, we show that anharmonicity and the large Grüneisen parameter in these oxychalcogenides are mainly related to the low frequency copper vibrations, rather than to the Bi(3+) lone pairs.

Tolerogenic CX3CR1+ B cells suppress food allergy-induced intestinal inflammation in mice.

BACKGROUND: B lymphocytes are an important cell population of the immune regulation; their role in the regulation of food allergy has not been fully understood yet. OBJECTIVE: This study aims to investigate the role of a subpopulation of tolerogenic B cells (TolBC) in the generation of regulatory T cells (Treg) and in the suppression of food allergy-induced intestinal inflammation in mice. METHODS: The intestinal mucosa-derived CD5+ CD19+ CX3CR1+ TolBCs were characterized by flow cytometry; a mouse model of intestinal T helper (Th)2 inflammation was established to assess the immune regulatory role of this subpopulation of TolBCs. RESULTS: A subpopulation of CD5+ CD19+ CX3CR1+ B cells was detected in the mouse intestinal mucosa. The cells also expressed transforming growth factor (TGF)-ß and carried integrin alpha v beta 6 (αvß6). Exposure to recombinant αvß6 and anti-IgM antibody induced naive B cells to differentiate into the TGF-ß-producing TolBCs. Coculturing this subpopulation of TolBCs with Th0 cells generated CD4+ CD25+ Foxp3+ Tregs. Adoptive transfer with the TolBCs markedly suppressed the food allergy-induced intestinal Th2 pattern inflammation in mice. CONCLUSIONS: CD5+ CD19+ CX3CR1+ TolBCs are capable of inducing Tregs in the intestine and suppress food allergy-related Th2 pattern inflammation in mice.

The relationship between management safety commitment and patient safety culture.

AIM: The study aims to explore the relationship between management safety commitment and patient safety culture using data from a Chinese hospital. BACKGROUND: Developing a positive patient safety culture has been suggested as an important strategy to improve the quality of health services and patient safety. Management safety commitment has been identified as key to establishing a culture of safety. However, little empirical evidence could be found in the literature to substantiate the relationship between management safety commitment and patient safety culture. Even less is known about the relationship in a Chinese hospital setting. METHODS: The study used a correlational research methodology with a cross-sectional survey design. A total of 248 registered nurses, including 20 nurse managers and 228 staff nurses, were surveyed using self-administered questionnaires. Both descriptive and inferential statistics were used to explore the relationship between management safety commitment and patient safety culture. FINDINGS: The mean score of safety commitment was 8.38 on a 0-10 visual analogue scale. The mean score of patient safety culture was 148.66. Staff nurses scored patient safety culture significantly lower than those of nurse managers (F = 18.88, P < 0.01). In addition, management safety commitment was significantly related to patient safety culture (r = 0.46, P < 0.01) and was an important predictor of patient safety culture (F = 65.29, P < 0.01). CONCLUSIONS: The findings provide significant empirical evidence that management safety commitment is associated with the culture of patient safety. Thus, to build a positive safety culture, managers need to visibly commit to patient safety and be a role model to ensure patient safety.

Mutations in the beta-myosin heavy chain gene in southern Chinese families with hypertrophic cardiomyopathy.

In this study, 14 unrelated hypertrophic cardiomyopathy (HCM) probands were scanned by polymerase chain reaction-single-strand conformation polymorphism analysis and DNA sequencing. Three mis-sense mutations of the beta-myosin heavy chain gene, MYH7, were found: valine (Val) 606 methionine (Met), arginine (Arg) 694 leucine (Leu), and Arg 723 glycine (Gly). All are reported here for the first time in Chinese subjects. The results showed that: Val606Met is an intermediate malignancy mutation; Arg694Leu is a novel mutation with a benign phenotype; and the Arg723Gly mutation is linked to malignancy - it can lead not only to HCM but also to dilated cardiomyopathy at various ages. The clinical symptoms associated with Arg723Gly emerged early and caused more severe clinical manifestation and poorer prognosis in females than in males. Mis-sense mutations were not detected in the myosin binding protein C, cardiac, cardiac troponin T type 2, or cardiac troponin I type 3 genes. The MYH7 gene may be an HCM mutation hotspot in the Chinese and have unique features in this study population.

Effect of yak milk casein hydrolysate on TH1/TH2 cytokines production by murine spleen lymphocytes in vitro.

Yak casein hydrolysate was derived from the enzymatic alcalase-hydrolysate of a typical northwestern China milk product called Qula. An in vitro study was conducted to examine their immunoregulatory effects on murine T cells, including Con-A-induced lymphoproliferation and splenocyte cell cycle, production, and messenger RNA (mRNA) expression of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and interleukin-4 (IL-4). The results showed that yak casein hydrolysate had lymphoproliferation activity on murine splenocytes and induced their cell cycle from the G1 to the S phase. It could increase Con-A-induced IL-2 and IFN-gamma production in spleen cells, but a very weak or no effect was observed in the absence of Con-A. The present study also showed that it could markedly increase the production and mRNA expression of IFN-gamma and IL-2, which are key cytokines for T helper 1 cell (Th1) cell development, in a dose-dependent manner. However, their effects on IL-4 secretion were not obvious, and the enhancement was much lower than that of IFN-gamma and IL-2. All of these demonstrated that yak casein hydrolysate could increase type 1 cytokine production, thereby shifting the Th1/T helper 2 cell (Th2) balance toward a Th1-dominant phenotype, which meant that yak casein hydrolysate could indeed not only modulate the differentiation of helper T cell but also has the capacity to modulate the Th1/Th2 balance. Therefore, yak casein hydrolysate may be useful for the treatment of cell-mediated immune diseases.

[Effect of simulated weightlessness on the apoptosis of thymus cells in tail-suspended mice].

OBJECTIVE: To investigate the effect of simulated weightlessness on apoptosis of thymus cells in mice. METHOD: Tail-suspended mice were used as an animal model of simulated weightlessness; chromosome breakage was measured by PI staining, and changes of cell membrane were determined by Annexin-V analysis. RESULT: As compared with the control, there was no obvious chromosome breakage; the total number of apoptotic cells and number of early apoptotic cells increased in 1 d suspended group; the number of early apoptotic cells increased significantly and the total number of apoptotic cells increased very significantly in 2d suspended groups. CONCLUSION: These results suggested that simulated weightlessness could promote apoptosis of thymus cells.

Genomic structure of human alpha-pix, and variable deletions in a poly (T) tract in gastric cancer tissue.

PAK-interacting exchange factor (PIX) has been reported to mediate the recruitment of PAK into focal adhesions and activate Rac, thus creating a feedback loop that stimulate PAK and other targets. This pathway is thought to be related to cellular changes, such as transformation and migration, that are often encountered in cancer cells. Here, we report the genomic structure of alpha-PIX, one of the PAK- interacting exchange factors, including the identification of the promoter region, which consisted 772 amino acids in 22 exons, spanning about 100 kb on genome of X chromosome. All splice sites conformed to the GT-AT rule. To investigate the role of alpha-PIX in carcinogenesis, we screened 60 cases of gastric cancer for mutations and polymorphisms using an intron-primer that covered all the exons, but no mutations or polymorphisms were found in the coding region. However an 18 bp repeat of thymidine tract was present in 50 bp downstream from exon 12 and the deletion of variable numbers of mononucleotide repeats was observed in seven out of the 60 gastric cancer tissue specimens that were examined. These seven cases all exhibited a mutator phenotype, suggesting that the deletions are passenger mutations. Thus our results revealed that alpha-PIX probably does not play any primary role in human gastric carcinogenesis.

Genomic structure and loss of heterozygosity of EPHB2 in colorectal cancer.

EphB2, a member of the Eph receptor protein-tyrosine kinase family, is overexpressed in several human gastrointestinal tumors. Furthermore, the EphB2 gene is localized at 1p35-p36.1, a frequently deleted region in colon and other cancers. So, despite its overexpression in some kind of tumors, we decided to study the possibility of involvement in the EphB2 gene (EPHB2) mutation in colon cancers, because some of the well known tumor suppressor genes (e.g. p53) is overexpressed (really accumulated) in tumors. Fifty colon tumor samples of matched with their respective normal tissues, were studied for mutation of the EPHB2. Analysis of the genomic structure of EphB2 and survey of all 16 exons revealed an infrequent polymorphism (intron 2) and mutation (intron 8). Another polymorphism in exon 6, localized at nucleotide 1359 (A-->G) was found to be rather frequent in Japanese and Chinese subjects, but very rare in Caucasians. Taking advantage of this polymorphism within EPHB2, we surveyed the loss of heterozygosity (LOH) status of this gene in Japanese colorectal tumors. Among the 50 samples analyzed, 24 were informative, and LOH was found in five of the15 (33.3%) informative rectal cancer cases. Mutation analysis covering all 16 exons in the remaining allele did not reveal any mutations. Thus, EPHB2 is not a classical tumor suppressor gene.

[Protective effects of Chinese herb-compound on cellular immunological function (correction of funcion) in tail-suspended rats].

Objective. To observe the protective effects of two kinds of Chinese herb-compounds (Dan-huang-ci compound and Shen-chuan-shu compound) on cellular immunology in tail-suspended rats. Method. The rats were divided into: 1) normal control group; 2) tail-suspended group; 3) tail-suspended + Dan-huang-ci compound; and 4) tail-suspended + Shen-chuan-shu compound. Ability of lymphocyte proliferation and production of IL-2 in rats in the four groups were compared after 21 d. Result. The immunological function of tail-suspended control group decreased significantly as compared with normal control group. Shen-chuan-shu compound could improve immunological function of tail-suspended rats obviously. Conclusion. Shen-chuan-shu compound could enhance cellular immunological function in rats under simulated weightlessness.

[Changes of femur minerals and serum BGP in hindlimb unloaded rats during convalescence].

Objective. To observe bone mass changes during convalescence after simulated weightlessness. Method. 7-week-old rats were tail-suspended for 21 d then reloaded for 7 d and 21 d to recover, and measured serum BGP. Result. Tail suspension of rats for 21 d caused significant decrease of serum BGP and phosphorus as well as femur minerals. Serum BGP and femur minerals were still lower than control levels, but serum contents of calcium, phosphorus and magnesium increased significantly after reloading for 7 d. Femur minerals and serum BGP, calcium, phosphorus and magnesium returned to control levels after reloading for 21 d. Conclusion. The deficit in femur mineral induced by hindlimb unloading in rats can be restored by return to normal weight bearing, BGP can be used to monitor the case of its recovery.

Interaction of human immunodeficiency virus-derived vectors with wild-type virus in transduced cells.

The interaction of human immunodeficiency virus (HIV)-derived vectors with wild-type virus was analyzed in transduced cells. Vector transcripts upregulated by infection had no measurable effect on HIV type 1 (HIV-1) expression but competed efficiently for encapsidation, inhibiting the infectivity and spread of HIV-1 in culture and leading to mobilization and recombination of the vector. These effects were abrogated with a self-inactivating vector.

[A comparative study of coronary arteriography and myocardial emission computed tomography in the diagnosis of coronary heart disease].

Both coronary arteriography (CAG) and myocardial emission computed tomography (ECT) were performed in 58 patients. According to CAG findings and clinical manifestations, 47 patients were diagnosed as coronary heart disease (CHD), while 11 not. CAG was abnormal in 39 patients of the 47. The sensitivity and specificity of CAG were 83% and 100% respectively. The diagnosis of CHD was made without any doubt in patients with abnormal CAG. The sensitivity of ECT was 97.9%, the specificity only 45.5%, and the predictive value of negative ECT 83.3%. Therefore, abnormal ECT should be closely related to the clinical manifestations in order to evaluate its significance and a normal ECT may rule out CHD with more reliability.

Secretion of myeloperoxidase isoforms by human neutrophils.

The human neutrophil lysosomal enzyme, myeloperoxidase (MPO), exists in three major and chromatographically distinct forms, MPO I, MPO II, and MPO III. We used cation-exchange medium-pressure liquid chromatography and kinetic microenzyme assay (or spectrophotometric monitoring) to analyze the secretion of MPO isoforms by neutrophils exposed to N-formylmethionylleucylphenylalanine (FMLP), digitonin, the ionophore A23187, and serum-opsonized zymosan A (SOZ). All three MPO isomers were released into the fluid phase after neutrophils were exposed to these secretagogues. A significant proportional increase in MPO I was released when neutrophils were stimulated with SOZ. MPO I was released in higher proportions than found in the whole cell constituency when neutrophils were stimulated with FMLP + cytochalasin B, A23187, and digitonin, but this was not statistically significant.

Effect of ouabain on the rabbit ear artery contraction to serotonin: enhanced response mediated by serotonergic rather than alpha adrenergic receptors.

The effect of ouabain on the rabbit ear artery response to serotonin was assessed in isolated vascular rings mounted in tissue baths for the measurement of isometric contractions and denervated with 6-hydroxydopamine in vitro. Ouabain, 1 and 10 microM, caused 5- and 6-fold shifts to the left of the serotonin concentration-response curve (CRC). However, 10 microM ouabain caused only a 1.6-fold shift to the left of the norepinephrine CRC. In the absence of ouabain, 0.01 microM ketanserin had little effect, whereas 0.1 microM prazosin caused a marked shift to the right of the serotonin CRC. In the presence of ouabain, prazosin exhibited little or no antagonism below 3 microM serotonin. Antagonism by ketanserin was increased by 1 and 10 microM ouabain, yielding 6.5- and 10.5-fold shifts to the right of the serotonin CRC, respectively. Benextramine pretreatment to inactivate alpha adrenoceptors nearly abolished the rabbit ear artery response to serotonin. However, in the presence of 10 microM ouabain, there was a substantial recovery of the response to serotonin, and this response was antagonized by ketanserin. These results are consistent with our hypothesis that serotonergic receptors are present in the smooth muscle cell membranes of the rabbit ear artery but are either uncoupled to the contractile mechanism or in a low efficacy state. In the presence of ouabain, these receptors either become coupled or convert to a high efficacy state and thereby contribute to the serotonin-induced contraction. Because the serotonin CRC was shifted to the left in the presence of ouabain, it is likely that most of the CRC was below the threshold concentration at which serotonin activates alpha adrenoceptors. Thus antagonism by prazosin was lost.