Integration of HiBiT into enteroviruses: A universal tool for advancing enterovirus virology research.

The utilization of enteroviruses engineered with reporter genes serves as a valuable tool for advancing our understanding of enterovirus biology and its applications, enabling the development of effective therapeutic and preventive strategies. In this study, our initial attempts to introduce a NanoLuc luciferase (NLuc) reporter gene into recombinant enteroviruses were unsuccessful in rescuing viable progenies. We hypothesized that the size of the inserted tag might be a determining factor in the rescue of the virus. Therefore, we inserted the 11-amino-acid HiBiT tag into the genomes of enterovirus A71 (EV-A71), coxsackievirus A10 (CVA10), coxsackievirus A7 (CVA7), coxsackievirus A16 (CVA16), namely EV-A71-HiBiT, CVA16-HiBiT, CVA10-HiBiT, CVA7-HiBiT, and observed that the HiBiT-tagged viruses exhibited remarkably high rescue efficiency. Notably, the HiBiT-tagged enteroviruses displayed comparable characteristics to the wild-type viruses. A direct comparison between CVA16-NLuc and CVA16-HiBiT recombinant viruses revealed that the tiny HiBiT insertion had minimal impact on virus infectivity and replication kinetics. Moreover, these HiBiT-tagged enteroviruses demonstrated high genetic stability in different cell lines over multiple passages. In addition, the HiBiT-tagged viruses were successfully tested in antiviral drug assays, and the sensitivity of the viruses to drugs was not affected by the HiBiT tag. Ultimately, our findings provide definitive evidence that the integration of HiBiT into enteroviruses presents a universal, convenient, and invaluable method for advancing research in the realm of enterovirus virology. Furthermore, HiBiT-tagged enteroviruses exhibit great potential for diverse applications, including the development of antivirals and the elucidation of viral infection mechanisms.

Massive fetomaternal hemorrhage in a monochorionic-diamniotic twin pregnancy: a case report.

Fetomaternal hemorrhage (FMH) result into severe, life-threatening fetal anemia and cause intrauterine death of the fetus. It is tough for an early diagnosis of FMH before pregnancy and few authors reported FMH in a twin pregnancy. Therefore, we reported a case of massive FMH. The patient felt a decrease in fetal movements at 33+5 gestational weeks. Cardiotocography showed sinusoidal heart rate patterns in one fetus. The fetal hemoglobin level in maternal blood was 6.4% (normal range for single pregnancy, 0.0%-2.0%). Since the patient was diagnosed with fetal distress, cesarean section was performed and both babies delivered to receive neonatal treatment. Severe anemia was apparent in both neonates, based on red blood cell count, hemoglobin concentration, and hematocrit of 0.75 × 1012/L and 0.61 × 1012/L, 2.8 g/dL and 2.4 g/dL, and 10.0% and 8.4%, respectively. The neonates were admitted to the intensive care unit for prematurity care and presently are well. In our experience, an early diagnosis of FMH contributed to saving fetus. Obstetricians should highlight fetal movements counting to every patient. Once massive FMH occurs in monochorionic twins, both fetuses may develop severe anemia and require emergency intervention.

Effects of Different Types of Fibers on the Physical and Mechanical Properties of MICP-Treated Calcareous Sand.

Microbial-induced calcite precipitation (MICP) has been a promising method to improve geotechnical engineering properties through the precipitation of calcium carbonate (CaCO3) on the contact and surface of soil particles in recent years. In the present experiment, water absorption and unconfined compressive strength (UCS) tests were carried out to investigate the effects of three different fiber types (glass fiber, polyester fiber, and hemp fiber) on the physical and mechanical properties of MICP-treated calcareous sand. The fibers used were at 0%, 0.10%, 0.15%, 0.20%, 0.25%, 0.30%, 0.35%, and 0.40% relative to the weight of the sand. The results showed that the failure strain and ductility of the samples could be improved by adding fibers. Compared to biocemented sand (BS), the water absorption of these three fiber-reinforced biocemented sands were, respectively, decreased by 11.60%, 21.18%, and 7.29%. UCS was, respectively, increased by 24.20%, 60.76%, and 6.40%. Polyester fiber produced the best effect, followed by glass fiber and hemp fiber. The optimum contents of glass fiber and polyester fiber were 0.20% and 0.25%, respectively. The optimum content of hemp fiber was within the range of 0.20-0.25%. Light-emitting diode (LED) microscope and scanning electron microscope (SEM) images lead to the conclusion that only a little calcite precipitation had occurred around the hemp fiber, leading to a poor bonding effect compared to the glass and polyester fibers. It was therefore suggested that polyester fiber should be used to improve the properties of biocemented sand.

Contribution of xeroderma pigmentosum complementation group D gene polymorphisms in breast and ovarian cancer susceptibility: A protocol for systematic review and meta analysis.

BACKGROUND: The role of xeroderma pigmentosum complementation group D (XPD) gene polymorphisms in breast and ovarian cancer development has long been controversial and existing data were inconsistent. Here, we conducted a comprehensive systemic review and meta-analysis to better clarify the association. METHODS: Relevant case-control studies published in electronic data base from October 1999 to September 2019 were assessed. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (95%CIs) were calculated by using Revman 5.2 software (Cochrane Collaboration, Copenhagen). RESULTS: 31 articles including 38 case-control studies and 2 XPD polymorphisms (rs1799793 and rs238406) were analyzed. The results showed statistical significance in heterozygous mutants among Asian population for rs1799793 (GA vs GG + AA: OR = 1.38, 95%CI = 1.21-1.56), and Caucasian population for rs238406 (CA vs AA + CC: OR = 0.63, 95%CI = 0.49-0.80), while the rest comparisons including overall groups and subgroups stratified by cancer types and ethnicity failed to indicate any association with breast and ovarian cancer risk. CONCLUSIONS: The current meta-analysis suggested no concrete correlation of XPD rs1799793(G/A) and rs238406(C/A) polymorphisms with breast cancer or ovarian cancer susceptibility. However, it indicated that heterozygous genotypes might share different pathophysiologic mechanism from not only homozygous wildtypes but also homozygous mutants. More case-control studies with well-adjusted data and diverse populations are essential for validation of our conclusion.

Combined Proinflammatory Biomarkers Have Better Predictive Value for Term Labor than Single Markers.

BACKGROUND The timing of parturition is an important determinant of labor and delivery care. Early parturition is associated with increased neonatal morbidity and mortality. Most existing studies analyzed a single factor for the initiation of parturition, and the role of multiple factors in initiating parturition has not been comprehensively analyzed. MATERIAL AND METHODS We measured the levels of proinflammatory mediators, hypoxia factor, matrix metalloproteinases, hormones, and oxytocin, as well as fetal umbilical blood flow, before and after labor, and their associations with parturition. We also built a statistical model to predict the timing of parturition based on the measurement data. RESULTS IL-1ß, IL-6, TNF-alpha, MMP-9, and HIF-1alpha concentrations significantly increased from full term to labor. The PRL level significantly decreased from full term to parturition. There was no significant change in MCP-1, E3, and OT concentrations from full term to parturition. IL-1ß, IL-6, TNF-alpha, and MMP-9 concentrations were negatively correlated with the initiation of parturition. There was a small but nonsignificant increase in umbilical venous blood flow before parturition. Multiple factors showed a close correlation with the initiation of parturition, and area under the curve analysis showed that a multiple factor model was superior to single factors in the establishment of a model to predict initiation of parturition; however, these results need further confirmation. CONCLUSIONS Combined proinflammatory biomarkers have better predictive value for term labor than single biomarkers.

Partial molar pregnancy in the cesarean scar: A case report and literature review.

RATIONALE: The incidence of molar pregnancy in the cesarean scar is exceedingly low, however, the disease may carry a high risk of uncontrolled hemorrhage or uterine rupture. So far managements of this disease were rarely reported in literature. PATIENT CONCERNS: We reported a 28-year-old woman presented to our hospital with a complaint of amenorrhea for 48 days and vaginal bleeding for 3 days. DIAGNOSIS: Transvaginal ultrasonography, serum hCG and pelvic MRI confirmed the cesarean scar pregnancy. INTERVENTIONS: The patient underwent bilateral uterine arterial embolization and suction evacuation. OUTCOMES: The postoperative histologic examination of the tissue revealed a partial hydatidiform mole. LESSONS: Molar pregnancy in the cesarean scar is tough to differentiate from normal cesarean scar pregnancy with serum hCG, sonogram or MRI. This case suggested us that it was necessary to perform a histological examination of postoperative specimen for cesarean scar pregnancy.

MicroRNA-224 suppresses osteoblast differentiation by inhibiting SMAD4.

Osteoblast differentiation was found to be regulated by a variety of cell signaling and intracellular regulatory factors. In this study, we aimed at investigating the regulatory effect of microRNA-224 on osteoblast differentiation and its molecular mechanism. Expression of miR-224 in the osteoblasts, adipose-derived mesenchymal stem cells (MSC-A), bone marrow-derived mesenchymal stem cells (MSC-B) and mbilical cord-derived mesenchymal stem cells (MSC-U) were detected using RT-PCR. Expression of miR-224 was lower in osteoblast than in the three mesenchymal stem cells and it revealed a decreasing time-dependent trend from 0 day to 28 days during osteoblast differentiation. By using alkaline phosphatase (ALP) activity assay and alizarin red S (ARS) staining, we found that the mineralization nodules decreased in miR-224-mimics group and increased in miR-224-inhibitor group. The Western blot detection of osteoblast markers, such as osteocalcin (OCN), osteopontin (OPN), bone sialoprotein (BSP), and runt related transcription factor 2 (RUNX2), also verified that overexpression of miR-224 inhibited osteoblast differentiation, while its inhibition promoted osteoblast differentiation. Luciferase reporter assay was performed in our study, which illustrated that miR-224 regulated SMAD4 directly by targeting SMAD4 3'UTR. Then after the inhibition of SMAD4, we found that lower expression of SMAD4 suppressed the osteoblast differentiation and the related signaling pathway using RT-PCR and Western blot. Our results revealed a new mechanism of osteoblast differentiation, and provided a new therapeutic agent to promote bone anabolism by targeting miR-224.

Liver resection for intermediate hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. The Barcelona Clinic Liver Cancer (BCLC) staging system is regarded as the gold standard staging system for HCC, classifying HCC as early, intermediate, or advanced. For intermediate HCC, trans-catheter arterial chemoembolization (TACE) is recommended as the optimal strategy by the BCLC guideline. This review investigates whether liver resection is better than TACE for intermediate HCC. Based on published studies, we compare the survival benefits and complications of liver resection and TACE for intermediate HCC. We also compare the survival benefits of liver resection in early and intermediate HCC. We find that liver resection can achieve better or at least comparable survival outcomes compared with TACE for intermediate HCC; however, we do not observe a significant difference between liver resection and TACE in terms of safety and morbidity. We conclude that liver resection may improve the short- and long-term survival of carefully selected intermediate HCC patients, and the procedure may be safely performed in the management of intermediate HCC.

Anticoagulant management of pregnant women with mechanical heart valve replacement during perioperative period.

OBJECTIVE: To investigate the morbidity of complications and pregnancy outcomes in women with mechanical heart valve replacement who received low-dose oral anticoagulation treatment with warfarin throughout the pregnancy, compare the prognosis and complications of patients who were treated with single oral warfarin treatment or the "bridging" therapy treatment, investigate the influence of using vitamin K1 before emergency cesarean section delivery on postoperative warfarin anticoagulant effect and to explore an appropriate anticoagulant regimen during perioperative period for pregnant women with mechanical heart valve replacement. METHOD: 46 pregnant women with mechanical heart valve replacement who received low-dose oral anticoagulation treatment from October 2008 to October 2014 treated at West China Women's and Children's Hospital were retrospectively reviewed. Eight patients received emergency cesarean section (CS), while 38 patients received selective CS, in which 17 patients received single oral warfarin and 21 patients received "bridging" anticoagulation treatment during postoperative period. Morbidity of complications and the time to achieve the target INR after operation were compared. RESULTS: The mechanical valves were at the mitral position in 35 (76.09 %) patients, at the aortic position in 2 (4.35 %) patient and at both the mitral and aortic position in 9 (19.57 %) patients. 46 full-term healthy babies were delivered and no maternal thromboembolic was observed during pregnancy. There was no significant difference of the amount of uterine bleeding between single oral warfarin group and "bridging" treatment group during postpartum period. In single oral warfarin group, one valve thrombosis was observed and led to sudden death. No periphery thrombosis, hematoma, general hemorrhage or other sign of over-anticoagulation was observed. The INR increased more slowly in the group who received emergency CS with preoperative application of vitamin K1 than other two groups. CONCLUSION: The use of vitamin K1 preoperatively might result in warfarin resistance and discontinuation of warfarin therapy before selective CS might be more appropriate than application of vitamin K1. The "bridging" anticoagulation treatment which combines oral warfarin and subcutaneous LMWH might be more effective and safer than single oral warfarin therapy for patients with mechanical heart valve replacement during postoperative period, no matter selective or emergency CS. The safety of low-dose oral warfarin therapy throughout pregnancy is still under controversy.

Gene Polymorphisms of Toll-Like Receptor 9 -1486T/C and 2848G/A in Cervical Cancer Risk.

OBJECTIVE: This work aims to explore whether Toll-like receptor 9 (TLR9) -1486T/C and 2848G/A polymorphisms are associated with cervical cancer risk. METHODS: A comprehensive electronic search of studies published from January 1999 to October 2014 was conducted in Medline (Ovid), Embase, PubMed, Wanfang, Weipu, and CNKI. The algorithm included "TLR," "Toll-like receptor," "polymorphism," "variant," "mutation," and "cervical cancer." Seven articles, including 9 studies, were pooled using Revman 5.2 (Cochrane Collaboration, Copenhagen, Denmark). Odds ratio (OR) was used to explore the involvement of minor allele C (C vs T and CC + CT vs TT) of TLR9 (-1486T/C, rs187084) and minor allele A (A vs G and AA + AG vs GG) of TLR9 (2848G/A, rs352140) in cervical cancer risk. RESULTS: Toll-like receptor 9 (-1486T/C, rs187084) polymorphisms were associated with an elevated risk of cervical cancer (C vs T: OR, 1.15; 95% confidence interval [CI], 1.03-1.29; CC + CT vs TT: OR, 1.30; 95% CI, 1.11-1.53). We found no significant association between TLR9 (2848G/A, rs352140) polymorphisms and cervical cancer risk (A vs G: OR, 1.15; 95% CI, 0.87-1.54; AA + AG vs GG: OR, 1.27; 95% CI, 0.75-2.17). CONCLUSIONS: This meta-analysis indicates that TLR9 (-1486T/C, rs187084)-but not TLR9 (2848G/A, rs352140)-may be a risk factor for cervical cancer.

Association between HSD17B1 rs605059 polymorphisms and the risk of uterine diseases: a systemic review and meta-analysis.

The aim of this study was to evaluate the HSD17B1 gene polymorphisms in the risks of endometrial cancer, endometriosis and uterine leiomyoma by meta-analysis. A comprehensive electronic search was conducted in PubMed, Medline (Ovid), Embase, Weipu, Wanfang and CNKI. The pooled ORs were performed using the Revman 5.2 softerware. 8 case-control studies were included: 3 were about endometrial cancer, 4 were about endometriosis and 1 was about uterine leiomyoma. The result showed no significant association between HSD17B1 rs605059 gene polymorphisms and risks of endometrial cancer (AA vs. AG+GG: OR = 1.11, 95% CI = 0.94-1.32; AA+AG vs. GG: OR = 1.79, 95% CI = 0.42-7.52; AG vs. AA+ GG: OR = 0.87, 95% CI = 0.76-1.00; AA vs. GG: OR = 1.43, 95% CI = 0.62-3.30; A vs. G: OR = 1.00, 95% CI = 0.91-1.11) or endometriosis (AA vs. AG+GG: OR = 0.99, 95% CI = 0.75-1.32; AA+AG vs. GG: OR = 1.73, 95% CI = 0.92-3.25; AG vs. AA+ GG: OR = 1.24, 95% CI = 1.00-1.53; AA vs. GG: OR = 1.54, 95% CI = 0.79-2.97; A vs. G: OR = 1.23, 95% CI = 0.90-1.68). No association was found in a subgroup analysis based on Asian ethnicity for endometriosis. This meta-analysis suggested that HSD17B1 rs605059 polymorphisms were not associated with the risks of endometrial cancer and endometriosis. Further studies are needed to validate the conclusion and clarify the relationship between HSD17B1 rs605059 polymorphisms and the risk of uterine leiomyoma.

Increased expression of fibroblast growth factor receptor 1 in endometriosis and its correlation with endometriosis-related dysmenorrhea and recurrence.

OBJECTIVE(S): This study aims to identify a critical molecule that potentially participates in endometriosis pathogenesis and characterize its correlation with dysmenorrhea and recurrence. STUDY DESIGN: We utilized a bioinformatics-based strategy to screen for candidate genes and fibroblast growth factor receptor 1(FGFR1) was chosen for further validation. FGFR1 expression was examined in specimens of ectopic and eutopic endometrium obtained from 48 patients with endometriosis and specimens of eutopic endometrium from 26 healthy control subjects using immunohistochemistry and Western blotting. In addition, FGFR shRNA treatment was applied in a nude mice endometriosis model to examine the functional role of FGFR1 in endometriosis formation in vivo. RESULTS: FGFR1 was found commonly overexpressed in ectopic endometrium of endometriosis compared with either its eutopic counterpart or endometrium from normal patients (P < 0.05). FGFR shRNA treatment impaired endometriosis formation and alleviated endometriosis-related symptoms in vivo. FGFR1 expression in ectopic endometrium was correlated with dysmenorrhea severity (P < 0.05) and recurrence in endometriosis patients (P < 0.05). CONCLUSION(S): FGFR1 might be involved in endometriosis development, which could possibly serve as a novel therapeutic target and prognostic marker for this disease.

[The Effect of Fennel Tea Drinking on Postoperative Gut Recovery after Gynecological Malignancies Operation].

OBJECTIVE: To reveal if whether fennel fruit (Fructus Foeniculi) tea drinking enhances the recovery of intestinal function after gynecologic malignancies operation. METHODS: A total of 159 patients undergoing laparotomy for gynecological cancers were randomized into a tea group (n=78) and a control group (n=81). The patients in tea group drank a cup of fennel fruit tea while patients in control group drank the equal quantity of water twice per day from the first morning after operation until the first flatus. Every cup of tea consists of 5 gram of dried fennel fruit and 130 mL boiled water. The patents only drank the filtrate. Groups were compared in terms of time to first flatus and defecation, postoperative hospital stay, length of parenteral nutrition, ileus symptoms and other postoperative complications. RESULTS: Postoperative hospital [(5.6 +/- 1.2) d vs. (6.7 +/- 2.0) d, P<0.001], the mean time to flatus [(53.1 +/- 11.3) h vs. (64.2 +/- 13.6) h, P<0.001)], and the mean time to defecation [(4.3 +/- 1.0) d vs. (5.4 +/- 1.2) d, P < 0.001)] were significantly lower in tea group compared with those in control group. Ileus symptoms were observed more in patients in the control group compared to patients in tea group [relative risk = 2.6; 95% confidence interval, 1.5-4.5; P=0.001]. CONCLUSION: Fennel tea drinking after laparotomy for gynecological malignancis, an economical care, is safe, well to lerated and associated with rapider recovery of bowel motility, shorter hospital stay and fewer complications.

Growth and differentiation of neural stem cells in a three-dimensional collagen gel scaffold.

Collagen protein is an ideal scaffold material for the transplantation of neural stem cells. In this study, rat neural stem cells were seeded into a three-dimensional collagen gel scaffold, with suspension cultured neural stem cells being used as a control group. Neural stem cells, which were cultured in medium containing epidermal growth factor and basic fibroblast growth factor, actively expanded and formed neurospheres in both culture groups. In serum-free medium conditions, the processes extended from neurospheres in the collagen gel group were much longer than those in the suspension culture group. Immunofluorescence staining showed that neurospheres cultured in collagen gels were stained positive for nestin and differentiated cells were stained positive for the neuronal marker ßIII-tubulin, the astrocytic marker glial fibrillary acidic protein and the oligodendrocytic marker 2',3'-cyclic nucleotide 3'-phosphodiesterase. Compared with neurospheres cultured in suspension, the differentiation potential of neural stem cells cultured in collagen gels increased, with the formation of neurons at an early stage. Our results show that the three-dimensional collagen gel culture system is superior to suspension culture in the proliferation, differentiation and process outgrowth of neural stem cells.