[Genetic characterization analysis of the whole genome sequence of Coxsackievirus A8 associated with hand, foot and mouth disease in China].

Objective: To study the genomic sequence of Coxsackievirus A8 (CV-A8) associated with hand, foot and mouth disease (HFMD) from 2013 to 2018 in China and to analyze the genetic evolution of each coding region of the full-length genome. Methods: The genome sequences of 11 CV-A8 strains isolated from patients with HFMD in different regions of China from 2013 to 2018 were determined. Sequence alignment and genetic evolution analysis were performed by Sequencher 5.0 and MEGA 7.0 software, etc. Results: Sequence alignment showed that the genome length of 11 CV-A8 strains ranged from 7 393 bp to 7 400 bp. There was no base insertion or deletion in the coding region compared with the prototype strain, but there were individual base insertion or deletion in the non-coding region. The nucleotide and amino acid similarities in the VP1 region of 11 CV-A8 strains were 78.3%-98.6% and 92.6%-99.7%, respectively, and the nucleotide and amino acid sequences identities with the CV-A8 prototype strain were 78.3%-98.2% and 92.6%-99.7%, respectively. Based on the phylogenetic analysis of VP1 region sequences, the CV-A8 can be divided into five genotypes: A, B, C, D and E. The 11 CV-A8 strains in this study belonged to genotypes C (1 strain), D (2 strains) and E (8 strains). The nucleotide and amino acid similarities of 11 CV-A8 full-length genomes were 81.3%-98.8% and 95.9%-99.5%, respectively. The phylogenetic tree of the P2 region showed that the eight E genotypes CV-A8 had the closest evolutionary distance with CV-A4, CV-A14, and CV-A16. The phylogenetic tree of the P3 region showed that the eight E genotypes CV-A8 had a close evolutionary distance with CV-A5, CV-A16, CV-A14 and CV-A4. Conclusions: The 11 CV-A8 stains in this study showed significant intra-genotype diversity in capsid region and recombinant diversity in non-capsid region which indicated that CV-A8 quasispecies were still undergoing dynamics variation. CV-A8 may become an important pathogen of HFMD and the monitoring of CV-A8 needs to be further strengthened.

[Clinical prognostic analysis of 124 adult patients with hemophagocytic lymphohistiocytosis: a multicenter retrospective study of the Huaihai Lymphoma Working Group].

Objective: Factors influencing the prognosis of hemophagocytic lymphohistiocytosis (HLH) in adults were analyzed based on multicentric data. Methods: Clinical data of 124 adult patients with HLH diagnosed in eight medical centers in the Huaihai Lymphoma Working Group from March 2014 to July 2020 were collected. The optimal truncation value of continuous variables was obtained based on the Maxstat algorithm, X-Tile software, and restricted cubic spline. Cox proportional risk regression model was used to construct the adult HLH risk prediction model, and the visualization of the model was realized through the histogram. The bootstrap resampling method was used to verify the model, C-index and calibration curve was used to verify the histogram, and the prediction accuracy was checked. Kaplan-Meier analysis was used to calculate the survival rate and draw the survival curve. Furthermore, the differences between groups were tested by log-rank. Results: The median age of the 124 patients was 55 (18-84) years, including 61 (49.19%) males. The most common etiology was infection. Serum ferritin increased in 110 cases (88.71%) , hepatosplenomegaly in 57 cases (45.97%) . Of the 124 patients, 77 (62.10%) died, and the median survival time of the patients was 7.07 months. Univariate results showed that the prognosis of adult HLH was influenced by sex, age, fibrinogen, serum creatinine, alanine aminotransferase, and albumin (P<0.05) . The results of multivariate analysis showed that gender, platelet, albumin, alanine aminotransferase, and treatment regimens were independent influencing factors for prognosis. Based on the above five risk factors, the prediction model of the histogram was established, and the C-index of the model was 0.739. Finally, the calibration chart showed good consistency between the observed and predicted values of HLH. Conclusion: The prognosis of the adult hemophagocytic syndrome is influenced by many factors. Gender, platelet, albumin, alanine aminotransferase, and treatment regimens are independent risk factors. Therefore, the established histogram provides a visual tool for clinicians to evaluate the prognosis of adult HLH.

[Studies of the norm of Karitane Parenting Confidence Scale(KPCS)among parents of infants in urban areas of China].

Objective: To establish the norm of the Chinese version of Karitane Parenting Confidence Scale (KPCS) in urban areas of China. Methods: From August to December 2017, the parents of 2 216 children (<36 months old) were selected from 15 cities (Beijing, Lianyungang, Hangzhou, Chengdu, Xi'an, Guangzhou, Changsha, Jinan, Guiyang, Ningbo, Dalian, Qinhuangdao, Maanshan, Chongqing and Wuhan) in 14 provinces by stratified random sampling. The general demographic characteristics and parents' parenting confidence were collected by a self-made questionnaire and KPCS Chinese version. The percentile norm was established. P3, P10 and P25 were used as the criteria to define the degree of lack of parenting confidence. Results: The age of mothers was (30.67±4.29). The age of the father was (32.50±4.99) years old. There were 726 (32.76%), 759 (34.25%) and 731 (32.99%) infants in 6-12, 12-23 and 24-35 months old groups. The total scores of P50, P25, P10 and P3 of KPCS (Chinese version) of infant parents in urban areas in China were 41, 38, 33, and 29 respectively. When the scores of parents were 34-37, 30-33, and ≤ 29, they were judged as mild, moderate, and severe lack of parenting confidence. There was no significant difference in the Chinese version of KPCS between parents of different age groups and parents of different gender (χ²=3.53, P=0.171; χ²=1.41, P=0.236). Each factor score≤P3 is defined as the boundary score, and the corresponding boundary scores of "parenting" "support" and "competence" were 13, 9, and 5 respectively. Conclusion: The Chinese version of KPCS can be used to assess the parenting confidence of infants in urban areas of China. It can used as one of the bases for scientific and objective evaluation of the parenting status of families.

MiR-5195-3p inhibits the proliferation of glioma cells by targeting BIRC2.

OBJECTIVE: The aim of this study was to investigate the effects of microRNA-5195-3p (miR-5195-3p) on the proliferation of glioma cells and to explore its related mechanisms. PATIENTS AND METHODS: The expression level of miR-5195-3p in glioma tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Online prediction websites (TargetScan and miRanda) were used to screen the potential targets of miR-5195-3p. Luciferase reporter gene assay and Western blot were performed to confirm the targets of miR-5195-3p. Furthermore, the effects of miR-5195-3p on cell proliferation were detected by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), colony formation assay, and flow cytometry, respectively. RESULTS: MiR-5195-3p was lowly expressed in both glioma tissues and cells. Baculoviral IAP repeat-containing 2 (BIRC2) was identified as a direct target of miR-5195-3p. Over-expression of miR-5195-3p in glioma cells significantly decreased the protein expression of BIRC2. Besides, the proliferative capacity and colony formation ability were significantly inhibited after transfection of miR-5195-3p in vitro. In addition, flow cytometry indicated that an evident G1 phase arrest occurred in miR-5195-3p over-expressed group. CONCLUSIONS: In this work, we emphasized the suppressor function of miR-5195-3p in the proliferation of glioma cells. Furthermore, our findings provided an experimental basis for the research and treatment of glioma.

[Practice of parenting and related factors on children aged 0-5 in the urban areas of China].

Objective: To characterize the relations between the practice of parenting and associated factors on children (0-5 years old) in urban areas of China, in order to provide evidence for promoting the early development of children and to provide positive guidance and service programs on parenting. Methods: A total of 4 515 parents from 15 cities (14 provinces) were surveyed with a self-administered questionnaire. Parenting and Family Adjustment Scales (PAFAS) was used, including parameters as: consistency and coercive parenting, positive encouragement, parent-child relationship and parental emotion adjustment, family relationship and parental teamwork aspects, etc. Both single factor analysis and multiple linear regression were used to examine the associations between parenting practice, individual, parental and family factors. Results: The mean score of PAFAS was 21.00 (15.00-28.00), associated with factors as children's age, only-child family, premature delivery, father's education level, confidence on parenting, problems regarding the parental mood, annual family income, family structure and behavior on seeking professional help, etc. Results showed that there were big differences on the practice of parenting in China and influenced by variety of factors. Conclusions: The general situation of parenting was well, in the urban areas of China. The practice of parenting was associated with a series of individual, parental and family factors. Programs on improving the parenting skills and promoting the early development of children, should be highlighted.

Estrogen and progesterone promote breast cancer cell proliferation by inducing cyclin G1 expression.

Breast cancer is the most common cause of cancer among women in most countries (WHO). Ovarian hormone disorder is thought to be associated with breast tumorigenesis. The present study investigated the effects of estrogen and progesterone administration on cell proliferation and underlying mechanisms in breast cancer MCF-7 cells. It was found that a single administration of estradiol (E2) or progesterone increased MCF-7 cell viability in a dose-dependent manner and promoted cell cycle progression by increasing the percentage of cells in the G2/M phase. A combination of E2 and progesterone led to a stronger effect than single treatment. Moreover, cyclin G1 was up-regulated by E2 and/or progesterone in MCF-7 cells. After knockdown of cyclin G1 in MCF-7 cells using a specific shRNA, estradiol- and progesterone-mediated cell viability and clonogenic ability were significantly limited. Additionally, estradiol- and progesterone-promoted cell accumulation in the G2/M phase was reversed after knockdown of cyclin G1. These data indicated that estrogen and progesterone promoted breast cancer cell proliferation by inducing the expression of cyclin G1. Our data indicated that novel therapeutics against cyclin G1 are promising for the treatment of estrogen- and progesterone-mediated breast cancer progression.

Soft Tissue Regeneration under the Effect of Wound Coating Based on Chitosan (Natural Biopolymer).

We developed wound coating based on natural biopolymer chitosan with additional components (ceruloplasmin, L-asparaginic acid, and glycerol). Experiments on albino male rats demonstrated its regeneratory, antioxidant, and antibacterial effects on wounds involving all layers of the skin. Due to chemical composition and buffer component, the biodegraded wound coating optimizes all phases of the wound process, accelerates by 22-28% the reparative regeneration, and leads to anatomic and functional restoration of injured sites. High absorption capacity recommends its use in the treatment of wounds with profuse exudation.

[ADAPTIVE REMODELLING OF BONE TISSUE IN TOTAL HIP REPLACEMENT].

Instrumental and laboratory monitoring of bone tissue adaptive remodeling processes after total hip replacement conducted for primary osteoarthrosis patients (32 males and 48 females) (coxarthrosis stage III, functional insufficiency stages II and III) with long-lasting joint damage, significant pain syndrome and osteodeficit, indicated osteodeficit intensification compared to the baseline in the implant surrounding areas. These patients showed an increasing cytokine imbalance in the blood serum postsurgically with the primary activation of proinflammatory (osteoresorbing) element and secondary activation of anti-inflammatory element. Structural and functional characteristics of bone tissue in the area adjacent to the implant and cytokine balance indexes in the blood serum did not return to the baseline even 12-15 months postsurgically.

Unfolded protein response suppresses cisplatin-induced apoptosis via autophagy regulation in human hepatocellular carcinoma cells.

It has been shown that drug resistance is extremely common in hepatocellular carcinoma (HCC) and is one of the major problems in HCC chemotherapy. However, the detailed mechanisms remain largely unknown. We have previously shown that endoplasmic reticulum (ER) stress is involved in the tumorigenesis of HCC. Here, we demonstrated that the unfolded protein response (UPR) inhibits cisplatin-induced HCC cell apoptosis. In HCC cells, cisplatin treatment triggers the UPR, which subsequently inhibits cisplatin-induced apoptosis. Importantly, mild ER stress precondition suppresses the sensitivity of HCC cells to cisplatin-induced apoptosis through autophagy regulation. Furthermore, heat-shock protein 27 (Hsp27) is involved in the cytoprotective role of the UPR in cisplatin-induced apoptosis. We also demonstrated that Hsp27 inhibits cisplatin- induced HCC cell death through autophagy activation. Taken together, our results indicate that the UPR inhibits cisplatin-induced apoptosis in HCC cells, at least in part, by Hsp27-mediated autophagy activation.

PI3K/Akt promotes GRP78 accumulation and inhibits endoplasmic reticulum stress-induced apoptosis in HEK293 cells.

The potential pro-survival role of phosphatidylinositol 3-kinase (PI3K)/Akt during endoplasmic reticulum stress has been well-characterized. However, the detailed mechanisms remain largely unknown. Here, we showed that PI3K/Akt inhibition promoted endoplasmic reticulum stress-induced apoptosis in a glucose-regulated protein 78 (GRP78)-dependent manner. During endoplasmic reticulum stress, high levels of Akt phosphorylation were sustained for at least 18 h in HEK293 cells. Importantly, PI3K/Akt enhanced GRP78 accumulation through increasing its stability following endoplasmic reticulum stress. Furthermore, Akt1, but not Akt2 or Akt3, was involved in GRP78 stability regulation. These results suggest that PI3K/Akt inhibits endoplasmic reticulum stress-induced apoptosis in HEK293 cells, at least in part, by promoting GRP78 protein stability.