OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) for revealing the genetic etiology of fetuses with isolated ventricular septal defect (VSD). METHODS: From December 2017 to December 2020, 69 fetuses with isolated VSD were identified at the First Affiliated Hospital of Zhengzhou University. Meanwhile, 839 similar prenatal cases were selected from public databases including Wanfang data, Wanfang Medicine, and China National Knowledge Infrastructure (CNKI) by using keywords such as "Ventricular septal defect", "Copy number variation", and "Prenatal". A total of 908 fetuses with isolated VSD were analyzed. CNV-seq was carried out for 69 fetuses. RESULTS: Among the 908 fetuses, 33 (3.63%) were found to harbor pathogenic CNVs, which included 11 chromosomal aneuploidies (1.21%) and 22 pathogenic CNVs (2.42%). The pathogenic CNVs have involved 12 genetic syndromes, with those known to involve the heart development including 5 cases of 22q11.21 deletion syndrome, 2 cases of 4q terminal deletion syndrome, and 1 case of 9q subtelomere deletion syndrome. The outcome of pregnancies for 15 fetuses with pathogenic CNVs was known, of which 12 were terminated, and 3 had spontaneous closure of the ventricular septum after birth, but 1 of them had other abnormalities. CONCLUSION Fetuses with isolated VSD have a relatively high risk for chromosomal abnormalities, for which CNV-seq should be recommended.
Female ; Pregnancy ; Humans ; DNA Copy Number Variations ; Heart Septal Defects, Ventricular/genetics* ; 22q11 Deletion Syndrome ; Fetus

Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m² group (P_interaction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.
Humans ; Male ; Arsenic/urine* ; Creatinine ; East Asian People ; Testosterone/blood* ; Urinalysis ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged

Nasal spray can treat local diseases such as rhinitis, it also plays an important role in the treatment of systemic diseases including vaccine immunity. As a drug-device combination product, spray pattern is often used as the quality indicator of nasal spray to ensure its quality, plume geometry can not only be combined with the spray pattern to evaluate the performance of the nasal spray, but also can predict the deposition of the nasal spray in the nasal cavity. This article systematically reviews the definition and measurement methods of the spray pattern and plume geometry of nasal spray and their correlation with nasal deposition behavior. The measurement parameters of spray pattern and plume geometry are defined. The influence of formulation, device and trigger parameters on spray pattern and plume geometry is clarified. The correlation between various parameters and nasal deposition is analyzed. The measurement parameters are classified according to the size and shape of the spray. Plume angle is closely related to the deposition of drugs in the nasal cavity. Jet-like plume with a smaller plume angle can increase the navigation ability of the nasal spray in the curved anatomical structure of the nasal cavity, which is conducive to increase drug deposition. This makes it possible to increase deposition of the nasal spray in the nasal cavity via appropriately increasing viscosity and thixotropy of the nasal spray formulation. This review provides the theoretical basis for the high quality nasal spray product development.

OBJECTIVE: To assess the diagnostic value of copy number variation sequencing (CNV-seq) in the genetic etiology of fetuses with nasal bone dysplasia (NBD). METHODS: A total of 217 fetuses discovered with NBD from December 2017 to December 2020 were divided into the isolated NBD group and NBD combined with other anomalies group, for which copy number variations (CNVs) were analyzed. RESULTS: A total of 40 fetal abnormalities were detected in 217 cases, with an overall abnormal rate of 18.4%. These included 31 cases with aneuploidies (14.3%, 31/217) and 9 cases with genomic CNVs (4.1%, 9/217). Five cases of trisomy 21 (3.5%, 5/144) and two CNVs cases with unknown clinical significance (1.4%, 2/144) were detected in the isolated group. As for the combined NBD group, 26 aneuploidies (35.6%, 26/73), including 19 cases with trisomy 21, 6 cases with trisomy 18, 1 case with trisomy 13, 5 cases with pathogenic CNVs (6.8%, 5/73), and 2 cases with CNVs of unknown clinical significance (2.7%, 2/73) were detected. A significant difference was detected between the two groups (P < 0.01). CONCLUSION The detection rate of CNV-seq is high for chromosomal aneuploidies and pathogenic CNVs in fetuses with NBD, particularly in those combined with other ultrasonic abnormalities.
Aneuploidy ; Bone Diseases, Developmental ; Chromosome Aberrations ; DNA Copy Number Variations ; Down Syndrome/genetics* ; Female ; Fetus/abnormalities* ; Humans ; Pregnancy ; Prenatal Diagnosis ; Trisomy

Objective: To investigate the incidence and clinical features to probe the risk factors of hemorrhagic cystitis (HC) in children and adolescents with hematological diseases post haplo-hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Medical records of 62 children and 27 adolescents with hematological diseases treated with haplo-HSCT between 2015 and 2016 were analyzed. Results: Of 89 cases (56 boys and 33 girls) , 44 patients were diagnosed with ALL, 33 AML, 3 AHL and 9 MDS. HC occurred in 32 of the 89 patients with an incidence of 36%, including 6 with grade Ⅰ, 16 with grade Ⅱ, 8 with grade Ⅲ, 2 with grade Ⅳ HC, respectively. The median time of HC onset was 25 days (range 2-55 days) after haplo-HSCT with the median duration as 19 days (range 3-95 days) , all of them were cured. The incidence of HC was lower in the group of children than that in the group of adolescents (27.4% vs 55.6%, χ(2)=6.466, P<0.05) , and the incidence of HC was higher in the group of patients who were ≥5 years old than that in the group of patients who were <5 years old (0 vs 34%, χ(2)=4.043, P<0.05) . Conclusion: HC is one of common complications in children and adolescents with hematological diseases post haplo-HSCT, older age was associated with increased mortality.
Adolescent ; Child ; Child, Preschool ; Cystitis ; Female ; Hematologic Diseases ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Male ; Retrospective Studies ; Risk Factors

Objective: To analyze the risk factors for metastasis of lymph nodes between sternocleidomastoid and sternohyoid muscle (LNSS) in papillary thyroid cancer (PTC). Methods: Papillary thyroid cancer patients with clinically positive lateral lymph node metastasis (cN1) who underwent surgery including LNSS dissection between May 1, 2013 and May 31, 2016 at the Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center were retrospectively studied. Logistic regression analysis was performed to evaluate possible clinicopathological factors related to LNSS metastasis. Results: In 85 patients, 54 patients (63.5%) showed LNSS in their surgical specimen, and 20 patients (23.5%) had pathologically positive LNSS metastasis. Patients with LNSS showed preoperatively higher levels of serum thyroid stimulating hormone (TSH) and thyroid peroxidase antibody (TPO-Ab) compared to patients only with fibrofatty tissues between sternocleidomastoid and sternohyoid muscle (P<0.05), and they also displayed a higher proportion of multifocality in ipsilateral thyroid lobe (P<0.05). Multi-factor analysis indicated that LNSS metastasis was correlated with original tumor size (OR=1.819, 95%CI 1.050-3.850, P=0.002) and Level Ⅳ lymph node metastasis (OR=2.190, 95%CI 1.132-2.334, P=0.005). Furthermore, the number of positive LNSS was tightly correlated to that of level Ⅳ lymph node metastasis(P<0.05). Conclusion LNSS metastasis is occult but not quite rare in PTC. Patients with extensive lymph node metastasis in Level Ⅳhave a higher risk for metastasis of LNSS.

Objective: To study the expression of long noncoding RNA (lncRNA) H19 in human prostate cancer tissue and its effect on the glycometabolism and growth of human prostate cancer cells. METHODS: Realtime quantitative RTPCR (qRTPCR) was employed to detect the expression of lncRNA H19 in human prostate tissues from 20 patients with prostate cancer (10 cases of highGleason score prostate cancer ［HGPC］ and 10 cases of lowGleason score prostate cancer ［LGPC］) and another 5 with benign prostatic hyperplasia (BPH). After transfection of H19 siRNA into the DU145 and PC3 prostate cancer cells, the growth of the cells and the H19 expression in the cells were determined by MTT and qRTPCR respectively, and the changes in the glycometabolism of the prostate cancer cells were analyzed by measuring the contents of glucose and lactate in the culture medium. Nontransfected and transfected negative vectors were used as blank and negative controls respectively. RESULTS The relative expression of H19 was significantly increased in both the HGPC and LGPC tissues (0.725±0.385 and 2.086±0.542) as compared with that in the BPH tissue (0.210±0.068) (P< 0.01), even higher in the HGPC than in the LGPC tissue (P< 0.01). After transfection of H19 siRNA, the expressions of H19 were remarkably decreased in the DU145 and PC3 prostate cancer cells in comparison with those in the blank control and negative control groups (P< 0.01), and so were the proliferation of and the glucose and lactate levels in the DU145 and PC3 cells (P< 0.01).
Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glucose ; metabolism ; Humans ; Lactic Acid ; metabolism ; Male ; Prostate ; metabolism ; Prostatic Hyperplasia ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology ; RNA, Long Noncoding ; genetics ; metabolism ; RNA, Small Interfering ; Transfection

The present study was designed to determine the intestinal bacterial metabolites of trollioside and isoquercetin and their antibacterial activities. A systematic in vitro biotransformation investigation on trollioside and isoquercetin, including metabolite identification, metabolic pathway deduction, and time course, was accomplished using a human intestinal bacterial model. The metabolites were analyzed and identified by HPLC and HPLC-MS. The antibacterial activities of trollioside, isoquercetin, and their metabolites were evaluated using the broth microdilution method with berberine as a positive control, and their potency was measured as minimal inhibitory concentration (MIC). Our results indicated that trollioside and isoquercetin were metabolized by human intestinal flora through O-deglycosylation, yielding aglycones proglobeflowery acid and quercetin, respectively The antibacterial activities of both metabolites were more potent than that of their parent compounds. In conclusion, trollioside and isoquercetin are totally and rapidly transformed by human intestinal bacteria in vitro and the transformation favors the improvement of the antibacterial activities of the parent compounds.
Activation, Metabolic ; Anti-Bacterial Agents ; metabolism ; Bacteria ; metabolism ; Benzoates ; metabolism ; Biotransformation ; Gastrointestinal Microbiome ; Glucosides ; metabolism ; Humans ; Intestines ; microbiology ; Microbial Sensitivity Tests ; Models, Biological ; Quercetin ; analogs & derivatives ; metabolism

Three-dimensional (3D) culture of cells could closely mimic the in vivo situation with regard to cell function and microenvironment compared with plane monolayer cultured cells. In this paper, we established 3D culture of rat WB-F344 cells with rotary cell culture system (RCCS) to simulate microgravity environment, and examined cells proliferation, morphology, microstructure, E-cadherin protein quantity and mRNA expression of adhesion molecules by count the number of cells, optical microscope, transmission electron microscope and reverse transcriptase-polymerase chain reaction (RT-PCR). The results demonstrated that cells were polyhedron with lots of micovilli and mitochondria, which grow well and packed together densely to form irregular aggregates. Adjacent cells were connected with desmosome and tight junction. With the regard, the aggregates behaved 3D growth characteristics. Moreover, compared with control, mRNA level of Fibronectin and E-cadherin protein were increased, the changes maybe is the part mechanism in this microgravity simulated cells culture models which strengthened cells junction. This rotating 3D model might facilitate the study of interactions of cell-cell, cell-matrix and the mechanisms.
Animals ; Cadherins ; genetics ; Cell Adhesion ; Cell Culture Techniques ; methods ; Cell Proliferation ; Fibronectins ; genetics ; Rats ; Spheroids, Cellular ; ultrastructure ; Weightlessness Simulation

1 approximately 3 days old Piglet's primary preadipocytes in vitro were cultured and treated with 0micromol/L (control group), 10microlmol/L (lower dose group), 20micromol/L(middle dose group) and 50micromol/L, 100micromol/L (higher dose group) RES. Cell proliferation and viability were analyzed by MTT assay. The degree of differentiation and adipogenesis were measured by Oil Red O staining extraction assay and the expression of Sirt1 (sirtuin) mRNA were detected by RT-PCR. The results showed the optical density (OD) of MTT and Oil Red O staining were all decreased, especially treated by 50micromol/L, 100micromol/L RES at 72h and 96h (P < 0.01); the ratio of OD of the expression of Sirt1 mRNA to that of beta-actin mRNA were increased after treated by 100micromol/L RES (P < 0.01). RES can inhibit proliferation and differentiation of pig preadipocytes in certain degree. Higher dose of RES can markedly decrease adipogenesis and prevent preadipocytes differentiation into adipocytes, which may be in part associated with its effect on increasing the expression of Sirt1 mRNA.
Adipocytes ; cytology ; drug effects ; metabolism ; Animals ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; RNA, Messenger ; analysis ; Sirtuin 1 ; genetics ; Stem Cells ; drug effects ; Stilbenes ; pharmacology ; Swine ; Transcription, Genetic