Clinical application value of pre-pregnancy carrier screening in Chinese Han childbearing population.

BACKGROUND: To explore the clinical application value of pre-conception expanded carrier screening (PECS) in the Chinese Han ethnicity population of childbearing age. METHODS: The results of genetic testing of infertile parents who underwent PECS in the Reproductive Medicine Center of the Second Affiliated Hospital of Zhengzhou University, China, from September 2019 to December 2021, were retrospectively analyzed. The carrier rate of single gene disease, the detection rate of high-risk parents, and the clinical outcome of high-risk parents were statistically analyzed. RESULTS: A total of 1372 Chinese Han ethnicity patients underwent PECS, among which 458 patients underwent the extended 108-gene test, their overall carrier rate was 31.7%, and the detection rate of high-risk parents was 0.3%. The highest carrier rates were SLC22A (2.4%), ATP7B (2.4%), MMACHC (2.2%), PAH (1.8%), GALC (1.8%), MLC1 (1.3%), UNC13D (1.1%), CAPN3 (1.1%), and PKHD1 (1.1%). There were 488 women with fragile X syndrome-FMR1 gene detection, and 6 patients (1.2%) had FMR1 gene mutation. A total of 426 patients were screened for spinal muscular atrophy-SMN1, and the carrier rate was 3.5%, and the detection rate of parents' co-carrier was 0.5%. CONCLUSION: Monogenic recessive hereditary diseases had a high carrier rate in the population. Pre-pregnancy screening could provide good prenatal and postnatal care guidance for patients and preimplantation genetic testing for monogenic/single gene disorders (PGT-M) and prenatal diagnosis could provide more precise reproductive choices for high-risk parents.

Liraglutide attenuates palmitate-induced apoptosis via PKA/ß-catenin/Bcl-2/Bax pathway in MC3T3-E1 cells.

Liraglutide (LRG), one agonist of glucagon-like peptide-1 receptor (GLP1R), has multiple lipid-lowering effects in type 2 diabetes mellitus, however, studies on the role of LRG in saturated fatty acid-induced bone loss are limited. Therefore, our aim was to investigate whether LRG reduces palmitate (PA)-induced apoptosis and whether the mechanism involves PKA/ß-catenin/Bcl-2/Bax in osteoblastic MC3T3-E1 cells. MC3T3-E1 cells were treated with different concentrations of PA, LRG, or pretreated with Exendin 9-39 and H89, cell viability, intracellular reactive oxygen species (ROS), cAMP levels, apoptosis and the expression of protein kinase A (PKA) and phosphorylation of PKA (p-PKA), ß-catenin and phosphorylation of ß-catenin (Ser675)(p-ß-catenin), GLP1R, cleaved-capase 3, Bcl2-Associated X Protein (Bax) and B-cell lymphoma-2 (Bcl-2) along with expression of Osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were evaluated. PA treatment inhibited cell proliferation and cAMP levels, elevated intracellular ROS levels and promoted apoptosis, increased protein expressions of RANKL, Bax and cleaved-caspase3, meanwhile decreased protein expression of OPG and Bcl-2 in a dose-dependent manner. LRG inverted PA-induced apoptosis, increased cAMP levels, promoted expression of p-PKA, p-ß-catenin (Ser675) and reversed these gene expressions via increasing GLP1R expression. Pretreatment of the cells with Exendin 9-39 and H89 partially eradicated the protective effect of LRG on PA-induced apoptosis and gene expressions. Therefore, these findings indicated that LRG attenuates PA-induced apoptosis possibly by GLP1R-mediated PKA/ß-catenin/Bcl-2/Bax pathway in MC3T3-E1 cells. Our results point to LRG as a new strategy to attenuate bone loss associated with high fat diet beyond its lipid-lowering actions. LRG inhibits PA-mediated apoptosis via GLP1R-mediated PKA/ß-catenin/Bcl-2/ Bax pathway, while possibly enhances PA-inhibited differentiation by regulating the expression of OPG and RANKL.

The Upregulation of HAS2-AS1 Relates to the Granulosa Cell Dysfunction by Repressing TGF-ß Signaling and Upregulating HAS2.

HAS2 antisense RNA 1 (HAS2-AS1) is a long noncoding RNA that has increased expression in mature granulosa cells (GCs) and contributes to cumulus expansion by regulating HAS2 expression. However, the roles of HAS2-AS1 during the pathological process of polycystic ovary syndrome (PCOS) are still unclear. This study investigated the roles of HAS2-AS1 in patients with PCOS. Here, a significant upregulation of HAS2-AS1 was found in the primary GCs from patients with PCOS, which was positively correlated with the level of the protein HAS2. The knockdown of HAS2 restored the upregulation of HAS2-AS1 in promoting migration but could not restore the effects of HAS2-AS1 overexpression in promoting proliferation and repressing apoptosis. Transforming growth factor ß (TGF-ß) upregulated HAS2-AS1 levels, while HAS2-AS1 functioned as a feedback inhibition factor repressing TGF-ß signaling by inhibiting TGF-ß receptor type 2 (TGFBR2) expression. HAS2-AS1 bonded with EZH2 and guided the polycomb complex 2 to the TGFBR2 promoter region. HAS2-AS1 overexpression induced H3K27 hypermethylation in the TGFBR2 promoter region and then repressed TGFBR2 transcription in KGN cells and primary GCs. In conclusion, we identified for the first time that HAS2-AS1 is upregulated in patients with PCOS and represses TGF-ß signaling via inducing TGFBR2 promoter region hypermethylation, which allowed us to explore the pathological processes of PCOS.

Pre-fermentation of rice flour for improving the cooking quality of extruded instant rice.

Extruded instant rice (EIR) could not maintain an intact grain morphology during cooking, which seriously affected its cooking quality. The problem was solved by pre-fermentation of rice flour for 5-10 days. Consequently, the cooking loss was significantly reduced, while the hardness, stickiness and water absorption of EIR were significantly increased. The mechanism was that the gel network of EIR was strengthened by the following ways: (1) pre-fermentation significantly increased the total starch and amylose contents of rice flour due to the dissolution or leaching of lipids, ash and soluble proteins into the fermentation broth; (2) pre-fermentation degraded the amorphous region of starch granules by enzymes and organic acids, resulting in a molecular structure with lower polydispersity index and molecular weight, and higher proportion of long- and ultra-long branched chains of amylopectin. This kind of molecular structure was conducive to the formation of ordered double helix structures and strong gel network.

Insight into the Effect of Counterions on the Chromatic Properties of Cr-Doped Rutile TiO2-Based Pigments.

Rutile TiO2 pigments codoped with chromophore ion Cr3+ and various charge-balancing ions (i.e., counterions species of Sb, Nb, W and Mo) were prepared by a solid-phase reaction method. The effects of the counterions and calcination temperatures on the phase structure, color-rendering and spectroscopic properties, microstructure, and stability of the synthesized pigments were investigated in detail. The results showed that the introduction of 5-10% counterions improved the solubility of Cr3+ in the TiO2 lattice to form the single-phase rutile pigments calcined at 1100 °C for 2 h. The 10% Cr-doped pigment showed a dark brown color. Depending on the content and type of counterions, the color of the codoped pigments was tailored from yellow to reddish or yellowish-orange to black with different brightness and hue. The influence mechanism of counterions was ascribed to the lattice distortion and variation in the charge balance condition. It was found that the addition of Sb, Nb, or Mo resulted in a remarkable improvement in the NIR reflectance of pigments. The grain growth was inhibited with the codoping of Cr/Sb and Cr/Nb to achieve the nano-sized pigments. In addition, the prepared pigments exhibited good acid and alkali corrosion resistance as well as excellent stability and coloring performance in transparent ceramic glazes.

Estimation of the prevalence of type 2 diabetes in combination with diabetic kidney disease and identification of the associated factors in patients attending primary hospitals in Anhui Province, China.

OBJECTIVE: To evaluate the prevalence of type 2 diabetes mellitus (T2DM) with chronic kidney disease (DM-CKD) and identify the associated factors in patients attending primary hospitals in Anhui Province, China. METHODS: A multi-stage sampling method was used to collect the demographic information, general clinical data, and details of the kidney disease of patients in 2019 through a questionnaire survey, physical examination, and laboratory examination. RESULTS: A total of 1067 patients with T2DM were studied, of whom 345 had chronic kidney disease (CKD; 32.33%); 18.8%, 12.2%, 58.0%, 9.9% and 1.2% of the participants had stages 1 to 5 CKD. Fifty-point-three percent of the participants were female and they were 59 ± 11.3 years old. Multivariate regression analysis revealed that age, systolic blood pressure, the duration of diabetes, hyperlipidaemia, and smoking were associated with DM-CKD. The duration of diabetes was positively associated with body mass index, 2-hour postprandial glucose, fasting blood glucose concentration, glycosylated haemoglobin, total cholesterol concentration and triglyceride concentration. CONCLUSIONS: The incidence of DM-CKD is relatively high in primary hospitals in Anhui Province. Appropriate preventive and therapeutic measures should be instituted according to the age, the duration of diabetes, sex, hypertension, smoking habits, and lipidaemia of patients.

[Associations between interleukin-17A expression and epithelial-mesenchymal transition in patients with hepatocellular carcinoma].

OBJECTIVE: To detect the expression of interleukin-17A(IL-17A) in hepatocellular carcinoma (HCCs) tissues, and to analyze its relationship with clinicopathological characteristics and epithelial-mesenchymal transition (EMT). METHODS: The expression of IL-17A, E-cadherin, vimentin proteins and Snail mRNA were detected by immunohistochemistry and in situ hybridization histochemistry in the hepatocellular carcinoma (HCC) tissues of 74 patients. RESULTS: IL-17A staining was detected in 54.1% (40/74) specimens of human HCCs, but only 25.0% (5/20) in corresponding peritumoral tissues (P<0.05). The positive rate of IL-17A expression in HCC patients with grade III+IV and UICC stage III+IV tumors was significantly higher than those with grade I+II and UICC stage I+II tumors. The expression of IL-17A was positively correlated with portal vein tumor thrombus and microvascular invasion (all P<0.05). The 1- and 2-year recurrence-free survival rates were 27.6% and 17.2% in the patients with positive IL-17A expression, but 79.3% and 58.5% in IL-17A-negative HCCs. The 1- and 2-year overall survival rates were 69.0% and 27.8% in the cases with positive IL-17A expression, while 91.3% and 87.0% in IL-17A-negative cases. Patients with IL-17A-positive HCCs showed significantly shorter recurrence-free and overall survival compared with the patients with IL-17A-negative HCCs (P<0.05). Multivariate analysis indicated that IL-17A expression was an independent factor for recurrence-free and overall survival of HCCs. IL-17A-positive HCCs were characterized by increased expression of vimentin (r=0.492, P<0.01) or Snail (r=0.410, P<0.05) and loss of E-cadherin expression (r=-0.404, P<0.05). CONCLUSIONS: Our results suggest that IL-17A is closely related to epithelial-mesenchymal transition in hepatocellular carcinoma. IL-17A-positive hepatocellular carcinoma demonstrates more aggressive biological behavior, and IL-17A may serve as a potential prognostic marker for this cancer.