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Objective: To investigate the clinical efficacy of percutaneous screw fixation combined with minimally invasive transpedicular bone grafting and non-bone grafting in the treatment of thoracolumbar fractures., Methods: From Janury 2021 to June 2022, 40 patients with thoracolumbar fracture were divided into the experimental group and the control group. There were 26 patients in the experimental group, including 21 males and 5 females with an aberage age of (47.3±12.3) years old, who underwent percutaneous pedicle screw fixation combined with transpedicular autogenous bone grafting. In the control group, 14 patients received percutaneous pedicle screw fixation only. including 7 makes and 7 females with an average age of (50.2±11.2) years old. The operative time, intraoperative blood loss, anterior height ratio of injured vertebrae, Cobb angle, visual analogue score (VAS), MacNab scores, loosening or broken of the implants. were compared and analyzed., Results: There was no significant difference in operation time, intraoperative blood loss, VAS and anterior height ratio of injured vertebrae between the two groups. Compared with the preoperative results, VAS and anterior height ratio of injured vertebrae were improved statistically( P <0.05). For Cobb angle of injured vertebra, there was no significant difference between the two groups before surgery ( P =0.766). While at 1 week, 3 months and 12 months after surgery, there were statistically differences between the two groups (P values were 0.042, 0.007 and 0.039, respectively). The Cobb angle of injured vertebrae one year after operation was statistically decreased in both groups compared with that before surgery ( P <0.001). One year after surgery, the excellent and good rate of Macnab scores was 96.15% in the experimental group and 92.86% in the control group, and there was no statistical differences between the two groups ( P =0.648). There was one patient in the control group suffering superficial wound infection on the third day, which was cured by dressing change and anti-infection treatment. There were no postoperative screw loosening and broken in both groups., Conclusion: The two surgical methods have the advantages of less trauma, less pain and quicker recovery, which can restore the height of the injured vertebra, reconstruct the spinal sequence and reduce the fracture of the vertebral body. Transpedicular autogenous bone grafting can increase the stability of the fractured vertebra and maintain the height of the vertebra better after surgery, thus reducing the possibility of complications such as kyphosis, screw loosening and broken.

Identification of the causes for congenital heart disease (CHD) is a prerequisite for precise prevention and personalized treatment of CHD. Zhao et al. 1 show increased that gestational serum palmitic acid (PA) predisposes offspring to CHD by perturbating the MARS/K-Hcy/GATA4 signaling pathway., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The clinical application of anthracyclines such as doxorubicin (DOX) is limited due to their cardiotoxicity. N6-methyladenosine (m 6 A) plays an essential role in numerous biological processes. However, the roles of m 6 A and m 6 A demethylase ALKBH5 in DOX-induced cardiotoxicity (DIC) remain unclear. In this research, DIC models were constructed using Alkbh5 -knockout (KO), Alkbh5 -knockin (KI), and Alkbh5 -myocardial-specific knockout (ALKBH5 flox/flox, αMyHC-Cre ) mice. Cardiac function and DOX-mediated signal transduction were investigated. As a result, both Alkbh5 whole-body KO and myocardial-specific KO mice had increased mortality, decreased cardiac function, and aggravated DIC injury with severe myocardial mitochondrial damage. Conversely, ALKBH5 overexpression alleviated DOX-mediated mitochondrial injury, increased survival, and improved myocardial function. Mechanistically, ALKBH5 regulated the expression of Rasal3 in an m 6 A-dependent manner through posttranscriptional mRNA regulation and reduced Rasal3 mRNA stability, thus activating RAS3, inhibiting apoptosis through the RAS/RAF/ERK signaling pathway, and alleviating DIC injury. These findings indicate the potential therapeutic effect of ALKBH5 on DIC., Competing Interests: Authors declare that they have no competing interests., (© 2023 The Authors.)

Background Dilated cardiomyopathy (DCM), characterized by progressive left ventricular enlargement and systolic dysfunction, is the most common type of cardiomyopathy and a leading cause of heart failure and cardiac death. Accumulating evidence underscores the critical role of genetic defects in the pathogenesis of DCM, and >250 genes have been implicated in DCM to date. However, DCM is of substantial genetic heterogeneity, and the genetic basis underpinning DCM remains elusive in most cases. Methods and Results By genome-wide scan with microsatellite markers and genetic linkage analysis in a 4-generation family inflicted with autosomal-dominant DCM, a new locus for DCM was mapped on chromosome 15q13.1-q13.3, a 4.77-cM (≈3.43 Mbp) interval between markers D15S1019 and D15S1010, with the largest 2-point logarithm of odds score of 5.1175 for the marker D15S165 at recombination fraction (θ)=0.00. Whole-exome sequencing analyses revealed that within the mapping chromosomal region, only the mutation in the KLF13 gene, c.430G>T (p.E144X), cosegregated with DCM in the family. In addition, sequencing analyses of KLF13 in another cohort of 266 unrelated patients with DCM and their available family members unveiled 2 new mutations, c.580G>T (p.E194X) and c.595T>C (p.C199R), which cosegregated with DCM in 2 families, respectively. The 3 mutations were absent from 418 healthy subjects. Functional assays demonstrated that the 3 mutants had no transactivation on the target genes ACTC1 and MYH7 (2 genes causally linked to DCM), alone or together with GATA4 (another gene contributing to DCM), and a diminished ability to bind the promoters of ACTC1 and MYH7 . Add, the E144X-mutant KLF13 showed a defect in intracellular distribution. Conclusions This investigation indicates KLF13 as a new gene predisposing to DCM, which adds novel insight to the molecular pathogenesis underlying DCM, implying potential implications for prenatal prevention and precision treatment of DCM in a subset of patients.

Beta-cypermethrin (β-CYP) is a highly effective broad-spectrum insecticide that can potentially affect female reproduction. However, little is known about the effect of β-CYP on uterine decidualisation, which is a vital process by which the uterus provides a suitable microenvironment for pregnancy maintenance. Therefore, we focused on the effect and mechanism of β-CYP on endometrial decidualisation during early pregnancy in mice. The results indicated that the expression levels of HOXA10, BMP2, and IGFBP1 was significantly downregulated in the decidual tissue and primary endometrial stromal cells of pregnant and pseudopregnant mice following β-CYP treatment. Serum E 2 concentration was significantly increased, whereas P 4 concentration and oestrogen receptor (ERα) and progesterone receptor (PRA) expression were significantly downregulated following β-CYP exposure. The number of polyploid decidual cells was lower in the β-CYP-treated group. Furthermore, β-CYP significantly downregulated the protein expression levels of CDK4 and CDK6, and the mRNA expression levels of cyclin D3 and p21. The number of foetuses per female in the first litter was markedly reduced following exposure to β-CYP. In summary, early pregnancy exposure to β-CYP may result in defective endometrial decidualisation via compromised proliferation of uterine stromal cells and reduced expressions of cyclin D3, CDK4/6, and p21 in mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, we sequenced a bacteria isolate Pandoraea sp. 892iso isolated from a Phytophthora rubi strain which is an important plant pathogenic oomycete, identified through genome and combined the data with existing genomic data from other 28 the genus of Pandoraea species. Next, we conducted a comparative genomic analysis of the genome structure, evolutionary relationships, and pathogenic characteristics of Pandoraea species. Our results identified Pandoraea sp. 892iso as Pandoraea sputorum at both the genome and gene levels. At the genome level, we carried out phylogenetic analysis of single-copy, gene co-linearity, ANI (average nucleotide identity) and AAI (average amino acid identity) indices, rpoB similarity, MLSA phylogenetic analysis, and genome-to-genome distance calculator calculations to identify the relationship between Pandoraea sp. 892iso and P. sputorum. At the gene level, the quorum sensing genes ppnI and ppnR and the OXA-159 gene were assessed. It is speculated that Pandoraea sp. 892iso is the endosymbiont of the Oomycetes strain of Phytophthora rubi., Competing Interests: The authors have declared that no competing interests exist.

Although salinity stress is one of the principal abiotic stresses affecting crop yield, a suitable concentration of NaCl has proven to be useful for increasing crop quality. This study used low salinity (34 mmol/L NaCl) and high salinity (85 mmol/L) to cultivate purple sweetpotato. Using transcriptomics and metabolomics to profile the pathway indicated that glycometabolism, secondary metabolite biosynthesis and the starch catabolic process were the significant pathways under the salinity stress. Further research showed that purple sweetpotato could regulate genes related to the regulation of the cellular Na + , K + , and other ions concentration in response to the low salinity tolerance, but loses this ability under high salinity. Meanwhile, under low salinity, the activity of antioxidant enzymes and their related gene expression are maintained at a high level. The low salinity influences the monosaccharide composition as well as the content and regulation of genes related to starch synthesis. Quality analysis showed that the low salinity could increase the starch content and influence the amylopectin biosynthesis. It suggested that low salinity promotes substance accumulation. High salinity could increase the anthocyanins biosynthesis and low salinity had a significant impact on phenolic acid and flavonol. Finally, the gene expression levels also prove the low salinity could change the composition and content level of the purple sweetpotato. This study showed that an appropriate concentration of NaCl can be used as an elicitor for application in purple sweetpotato planting.

Breast cancer is the most common malignant tumour in women. Our research on alloimperatorin from Angelica dahurica showed that alloimperatorin inhibited breast cancer cell viability in a concentration- and time-dependent manner; it also showed that apoptosis and ferroptosis inhibitors significantly weakened the antisurvival effect of alloimperatorin. Alloimperatorin clearly induced breast cancer cell apoptosis and increased the activities of caspase-3, caspase-8, caspase-9, and poly (ADP-ribose) polymerase; it also caused significant mitochondrial shrinkage, promoted the accumulation of Fe 2+ , reactive oxygen species, and malondialdehyde, and significantly reduced mRNA and protein expression levels of SLC7A11 and GPX4, indicating that alloimperatorin induces ferroptosis. In addition, alloimperatorin significantly promoted Kelch-like ECH-associated protein 1 (Keap1) expression; although it did not affect the expression of PGAM5 (mitochondrial serine/threonine protein phosphatase) and apoptosis-inducing factor mitochondria associated 1 (AIFM1), it significantly reduced the phosphorylation level of AIFM1. After downregulating the expression of Keap1, PGAM5, or AIFM1, the inhibitory effect of alloimperatorin on cell viability was significantly weakened, indicating that alloimperatorin regulates the Keap1/PGAM5/AIFM1 pathway to promote oxeiptosis. Alloimperatorin significantly inhibited the invasion of breast cancer cells, while Keap1 siRNA or GPX4 overexpression vectors significantly enhanced cell invasion and effectively reversed the anti-invasive effect of alloimperatorin. Therefore, alloimperatorin induces breast cancer cell apoptosis, ferroptosis, and oxeiptosis, thereby inhibiting cell growth and invasion.

Background: Circulating galectin-3 (Gal-3) and aldosterone (ALD) are involved in fibrosis and inflammation. However, their potential value as predictors of atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) is unknown or controversial. Therefore, the aim of this study was to assess the relationship between baseline Gal-3, ALD levels, and AF recurrence in patients performing RFCA., Methods: 153 consecutive patients undergoing RFCA were included. Gal-3 and ALD were measured at baseline. Univariate and multivariate Cox regressions were performed to determine the predictors of AF recurrence. Receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) curve were used to assess the value of predictors., Results: There were 35 (22.88%) cases of AF recurrence after RFCA. The recurrence group had significantly higher preoperative serum levels of Gal-3 and ALD than the nonrecurrence group. Univariate and multivariate analysis showed that Gal-3 (HR = 1.28, 95% CI: 1.04-1.56, p = 0.02) and ALD (OR = 1.02, 95% CI: 1.00-1.03, p < 0.03) were significantly associated with AF recurrence after RFCA. The area under the curve (AUC) of preoperative serum Gal-3, ALD, and 2 combined to predict the recurrence of AF patients after RFCA was 0.636, 0.798, and 0.893, respectively, while sensitivity was 65.32%, 71.69%, and 88.61%, respectively and specificity was 77.46%, 78.53%, and 86.0%, respectively. Patients with Gal-3 above the cutoff value of 14.57 pg/ml had higher frequent AF recurrence than the patients with Gal - 3 ≤ 14.57 pg/ml (35% vs. 12%, p < 0.001) during a follow-up. Meanwhile, patients with ALD above the cutoff value of 243.61 pg/ml also had a higher AF recurrence rate than those with ALD ≤ 243.61 pg/ml (37% vs. 11%, p < 0.001) during a follow-up. The recurrence rate in patients with Gal - 3 > 14.57 pg/ml + ALD > 243.61 pg/ml was higher than that in patients with baseline Gal - 3 > 14.57 pg/ml or ALD > 243.61 pg/ml and patients with Gal - 3 ≤ 14.57 pg/ml + ALD ≤ 243.61 pg/ml (57% vs. 14% vs. 9%, p < 0.01, respectively)., Conclusion: AF recurrence after RFCA had higher baseline Gal-3 and ALD levels, and higher preoperative circulating Gal-3 and ALD levels were independent predictors of AF recurrence for patients undergoing RFCA, while combination of preoperative Gal-3 and ALD levels has higher prediction accuracy., Competing Interests: The authors indicated no potential conflicts of interest., (Copyright © 2022 Zhong-bao Ruan et al.)

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM., (© 2022. The Author(s).)

Long non-coding RNAs (lncRNAs), which belong to the non-protein-coding RNAs, are greater than 200 nt in length. Although they have been found to play crucial roles in the regulation of cell growth and development, cell metabolism and the development of diseases, they are rarely reported in decidualization. The objective of our study is to explore the expression of lincRNA AC027700.1 in the endometrium of early pregnant mice and its role in decidualization. The expression of AC027700.1 in uterine tissues at implantation sites and inter implantation sites on the 6th day of pregnancy were detected by qRT-PCR. The relative expression of AC027700.1 in an in vivo model of induced decidualization in pseudopregnant mice and in in vitro model of induced decidualization in primary stromal cells and nucleus/cytoplasmic fractions were detected by qRT-PCR. GO and KEGG analysis of downstream target genes were performed by GOseq and KOBAS, respectively. The results show that AC027700.1 expression is significantly increased in tissues at implantation sites on the 6th day of pregnancy and in decidualized endometrial tissues and stromal cells. Furthermore, AC027700.1 localizes in the nuclear fraction and the downstream targeted genes are mainly involved in autophagy, cell cycle and RNA transport pathways. This study revealed that lincRNA AC027700.1 may be involved in decidualization of endometrium in early pregnancy, but the specific role and regulatory mechanism remain to be further studied.

Background Atrial fibrillation (AF) is the most common form of clinical cardiac dysrhythmia responsible for thromboembolic cerebral stroke, congestive heart failure, and death. Aggregating evidence highlights the strong genetic basis of AF. Nevertheless, AF is of pronounced genetic heterogeneity, and in an overwhelming majority of patients, the genetic determinants underpinning AF remain elusive. Methods and Results By genome-wide screening with polymorphic microsatellite markers and linkage analysis in a 4-generation Chinese family affected with autosomal-dominant AF, a novel locus for AF was mapped to chromosome 1q24.2-q25.1, a 3.20-cM (≈4.19 Mbp) interval between markers D1S2851 and D1S218, with the greatest 2-point logarithm of odds score of 4.8165 for the marker D1S452 at recombination fraction=0.00. Whole-exome sequencing and bioinformatics analyses showed that within the mapping region, only the mutation in the paired related homeobox 1 ( PRRX1 ) gene, NM&#95;022716.4:c.319C>T;(p.Gln107*), cosegregated with AF in the family. In addition, sequencing analyses of PRRX1 in another cohort of 225 unrelated patients with AF revealed a new mutation, NM&#95;022716.4:c.437G>T; (p.Arg146Ile), in a patient. The 2 mutations were absent in 908 control subjects. Biological analyses in HeLa cells demonstrated that the 2 mutants had significantly diminished transactivation on the target genes ISL1 and SHOX2 and markedly decreased ability to bind the promoters of ISL1 and SHOX2 (2 genes causally linked to AF), although with normal intracellular distribution. Conclusions This study first indicates that PRRX1 loss-of-function mutations predispose to AF, which provides novel insight into the molecular pathogenesis underpinning AF, implying potential implications for precisive prophylaxis and management of AF.

The data presented here are related to the article entitled "Comparative analysis of Phytophthora genomes reveals oomycete pathogenesis in crops" [1]. These data contain the description of genomic structure of the two plant pathogens, P. fragariae and P. rubi and characterize several gene families associated with pathogenicity of them: P450, ACX gene families, CAZymes and effector. This data presents the relevant results of two newly sequenced P. fragariae and P. rubi , so as to provide data for further studies by researchers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article., (© 2021 The Authors. Published by Elsevier Inc.)

Purpose: To observe the regulation of baicalin on IKKα mediated MASPIN in Human oral keratinocytes (HOKs) inflammatory reaction, this study was to explore the molecular regulation mechanism of baicalin on oral mucosal inflammation., Methods: HOKs were stimulated by lipopolysaccharide (LPS) to mimic the inflammatory response of oral mucosal inflammation in vitro. CCK-8 assay was used to detect the toxicity of baicalin to HOKs; then different concentrations of baicalin were pre-treated to LPS-stimulated HOKs, enzyme-linked immunosorbent assays (ELISA) was used to detect the secretion of IL-6 and TNF-α in LPS-stimulated HOKs; reverse transcription polymerase chain reaction(RT-PCR) and Western blot assay were used to detect the regulatory effects of baicalin on gene and protein expression levels of IKKα mediated MASPIN in LPS-stimulated HOKs. SPSS 21.0 software package was used for statistical analysis of the data., Results: HOKs stimulated by 10 μg/mL LPS successfully simulated the inflammatory environment of oral mucosal inflammation. The concentration of baicalin between 1 μg/mL and 20 μg/mL had no toxic effect on HOKs. With the increasing concentration of baicalin, the expression of MASPIN increased gradually, while the expression of IKKα and inflammatory factors decreased gradually(P＜0.05)., Conclusions: Baicalin can decrease the expression of inflammatory factors in LPS-stimulated HOKs, down-regulate IKKα and up-regulate MASPIN.

The oomycete genus Phytophthora includes devastating plant pathogens that are found in almost all ecosystems. We sequenced the genomes of two quarantined Phytophthora species- P. fragariae and P. rubi . Comparing these Phytophthora species and related genera allowed reconstruction of the phylogenetic relationships within the genus Phytophthora and revealed Phytophthora genomic features associated with infection and pathogenicity. We found that several hundred Phytophthora genes are putatively inherited from red algae, but Phytophthora does not have vestigial plastids originating from phototrophs. The horizontally-transferred Phytophthora genes are abundant transposons that "transmit" exogenous gene to Phytophthora species thus bring about the gene recombination possibility. Several expansion events of Phytophthora gene families associated with cell wall biogenesis can be used as mutational targets to elucidate gene function in pathogenic interactions with host plants. This work enhanced the understanding of Phytophthora evolution and will also be helpful for the design of phytopathological control strategies., (© 2021 The Authors. Published by Elsevier Ltd.)

Background: Myocardial infarction (MI) triggers a strong inflammatory response that is associated with myocardial fibrosis and cardiac remodeling. Interleukin (IL)-1β and IL-18 are key players in this response and are controlled by NLRP3-inflammatory bodies. Oridonin is a newly reported NLRP3 inhibitor with strong anti-inflammatory activity. We hypothesized that the covalent NLRP3 inhibitor Oridonin could reduce IL-1β and IL-18 expression and ameliorate myocardial fibrosis after myocardial infarction in mice, improve poor heart remodeling, and preserve heart function., Methods: Male C57BL/6 mice were subjected to left coronary artery ligation to induce MI and then treated with Oridonin (1, 3, or 6 mg/kg), MCC950 (10 mg/kg), CY-09 (5 mg/kg) or saline three times a week for two weeks. Four weeks after MI, cardiac function and myocardial fibrosis were assessed. In addition, myocardial expressions of inflammatory factors and fibrotic markers were analyzed by western blot, immunofluorescence, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction., Results: Oridonin treatment preserved left ventricular ejection fraction and fractional shortening, and markedly limited the myocardial infarct size in treated mice. The myocardial fibrosis was lower in the 1 mg/kg group (15.98 ± 1.64)%, 3 mg/kg group (17.39 ± 2.45)%, and 6 mg/kg group (16.76 ± 3.06)% compared to the control group (23.38 ± 1.65)%. Moreover, similar with the results of Oridonin, MCC950 and CY-09 also preserved cardiac function and reduced myocardial fibrosis. The expression levels of NLRP3, IL-1β and IL-18 were decreased in the Oridonin treatment group compared to non-treated group. In addition, myocardial macrophage and neutrophil influxes were attenuated in the Oridonin treated group., Conclusions: The covalent NLRP3-inflammasome inhibitor Oridonin reduces myocardial fibrosis and preserves cardiac function in a mouse MI model, which indicates potential therapeutic effect of Oridonin on acute MI patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Rationale: Coronavirus disease 2019 (COVID-19) was first announced in Wuhan, and has rapidly evolved into a pandemic. However, the risk factors associated with the severity and mortality of COVID-19 are yet to be described in detail. Methods: We retrospectively reviewed the information of 1525 cases from the Leishenshan Hospital in Wuhan. Univariate and multivariate Cox regression analyses were generated to explore the relationship between procalcitonin (PCT) level and the progression and prognosis of COVID-19. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity in hospitalized patients and their PCT levels. Survival curves and the cumulative hazard function for COVID-19 progression were conducted in the two groups. To further detect the relationship between the computed tomography score and survival days, curve-fitting analyses were performed. Results: Patients in the elevated PCT group had a higher incidence of severe and critical severity conditions ( P < 0.001), death, and higher computed tomography (CT) scores. There was an association between elevated PCT levels and mortality in the univariate ((hazard ratio [1], 3.377; 95% confidence interval [2], 1.012-10.344; P = 0.033) and multivariate Cox regression analysis (HR, 4.933; 95% CI, 1.170-20.788; P = 0.030). Similarly, patients with elevated PCT were more likely to have critically severe disease conditions in the univariate (odds ratio [2], 7.247; 95% CI, 3.559-14.757; P < 0.001) and multivariate logistic regression analysis (OR, 10.679; 95% CI, 4.562-25.000; P < 0.001). Kaplan-Meier curves showed poorer prognosis for patients with elevated PCT ( P = 0.024). The CT score 1 for patients with elevated PCT peaked at day 40 following the onset of symptoms then decreased gradually, while their total CT score was relatively stable. Conclusion: PCT level was shown as an independent risk factor of in-hospital mortality among COVID-19 patients. Compared with inpatients with normal PCT levels, inpatients with elevated PCT levels had a higher risk for overall mortality and critically severe disease. These findings may provide guidance for improving the prognosis of patients with critically severe COVID-19., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

This retrospective analysis evaluated the interaction between Ki-67 and histological grade and their prognostic role in different breast cancer subtypes. In total, 2,573 breast cancer patients underwent surgery, and their histological grade and Ki-67 values were evaluated by breast pathologists. The median Ki-67 index was 15%, which was used as the cut-off for low/high Ki-67 expression. Recurrence-free survival (RFS) was calculated and compared, and the results indicated that Ki-67 expression was significantly associated with histological grade in all breast cancer patients (p < 0.001) and in each immunohistochemical (IHC)-based subtype (p < 0.001). Both high Ki-67 expression and grade 3 tumours were independent predictors of inferior RFS in all patients, especially in those with luminal-like tumours (p < 0.05). Ki-67 was an independent prognostic factor for RFS in grade 1, 2 patients with luminal-like tumours (adjusted hazard ratio [HR] = 1.92, 95% confidence interval [CI]: 1.22-3.03, p = 0.005), but not in the other subtypes. Similarly, histological grade predicted shorter RFS in patients with low Ki-67 expression who had luminal-like tumours (adjusted HR = 2.12, 95% CI: 1.13-3.99, p = 0.02) but not in the other subtypes. Conversely, Ki-67 showed no prognostic value for patients with grade 3 tumours and vice versa.

Embryo implantation is an essential and complex process in mammalian reproduction. However, little evidence has indicated the involvement of autophagy during embryo implantation. To determine the possible role of autophagy in uterine of pregnant mice during the peri-implantation stage, we first examined the expression of autophagy-related markers ATG5 and LC3 on day 4, 5, and 6 of pregnancy (D4, D5, and D6, respectively). Compared with expression on D4, downregulation of the autophagy-related markers was observed on D5 and D6, the days after the embryo attached to the receptivity endometrium. Further examination showed that autophagy-related markers ATG5, ATG12, LC3, cathepsin B, and P62 at the implantation site were significantly decreased when comparing with the inter-implantation site. Fewer number of autophagosomes at the implantation site were also observed by transmission electron microscopy. To confirm the functional role of autophagy during embryo implantation in mice, we administered the autophagy inhibitor 3-methyladenine and chloroquine to mice. After treated with 3-methyladenine, the expression of decidual markers HOXA10 and progesterone receptor were significantly reduced. Furthermore, a reduction in implantation sites and increase in the HOXA10 and PR protein levels were observed in response to chloroquine treatment. In addition, impaired uterine decidualization and dysregulation of the PR and HOXA10 protein levels was observed after autophagy inhibited by 3-methyladenine and chloroquine in in vivo artificial decidualization mouse model. In the last, LC3 and P62 were also observed in normal human proliferative, secretory, and decidua tissues. In conclusion, endometrial autophagy may be essential for embryo implantation, and it may be associated with endometrial decidualization during early pregnancy. KEY MESSAGE: • Autophagy-related markers were significantly decreased at implantation site. • Autophagy inhibition results in abnormal decidualization. • Autophagy is essential for embryo implantation.

Decidualization of endometrial stromal cells (ESCs) accompanied with embryo implantation is a key process in mammalian reproduction. Evidence suggests that maintenance of decidual cells function is essential. As a critical part in post-transcriptional gene regulation, microRNAs (miRNAs/miR) have been confirmed to be involved in decidualization. However, whether microRNAs regulate decidual cells function has not been reported. Aiming to clarify the role and potential mechanism of miRNAs in decidual cells, artificial induced decidualization model in mice was established. There are 94 differentially expressed miRNAs (≥two-fold change) between decidualized and non-decidualized tissues, including 60 upregulated and 34 downregulated miRNAs. Of the differentially expressed miRNAs, mmu-miR-21a is up-regulated. RT-qPCR also confirmed the up-regulation of mmu-miR-21a following decidualization in vivo and in vitro , and bioinformatic analysis and luciferase activity assay revealed Pdcd4 to be the target gene of mmu-miR-21a. Inhibition of mmu-miR-21a restrained secretory function of decidual cells induced by mESCs, accompanied with increase of Pdcd4 expression and resulted in the increase of cell apoptosis. In addition, we also determined the expression of hsa-miR-21 and Pdcd4 in human proliferative endometrial tissues and decidua tissues. hsa-miR-21 showed higher expression in human decidua tissues compared with proliferative endometrial tissues, while expression of Pdcd4 was contrary to that of hsa-miR-21. Similarly, cell apoptosis increased significantly in human endometrial stromal cell line in response to inhibition of hsa-miR-21. Collectively, we conclude that mmu-miR-21a/hsa-miR-21 may play a key role in regulating the function of decidual cells by inhibiting cell apoptosis through targeting Pdcd4., (© 2019 Chongqing Medical University. Production and hosting by Elsevier B.V.)

Embryo implantation is essential for normal pregnancy, and the process of decidualization is critical for embryo implantation. However, the mechanism of decidualization during early pregnancy is still unknown. Forkhead box O3a (FOXO3a) is the most important functional transcription factor of the forkhead box family and is a highly conserved transcription factor of apoptosis-related genes. In the mouse uterus, FOXO3a was found to be expressed regularly from Days 1-7 of early pregnancy. Upon further exploration, it was found that FOXO3a was expressed at significantly higher levels at the implantation site than at the interimplantation site on Days 5-7 of pregnancy. Under artificial decidualization, FOXO3a was highly expressed in the first and second decidual zones. After decidualization, the expression of FOXO3a was significantly increased both in vivo and vitro. In primary stromal cells, apoptosis was reduced by decreased expression of FOXO3a after inducing decidualization. Moreover, when FOXO3a-small interfering RNA was transfected into the uteri of mice, the expression of decidualization- and apoptosis-related factors was impaired. Thus, FOXO3a might play an important role in decidualization during early pregnancy, and cell apoptosis might be one of pathways for FOXO3a-regulated decidualization., (© 2018 Wiley Periodicals, Inc.)

Dianthus chinensis is a perennial herbaceous plant with great ornamental, botanical, ecological, and medicinal value. The pistil of D. chinensis is composed of two fused carpels with free central placenta and two separate styles. The placenta is a columnar structure extending about two-thirds the length of the maturing fruit, which is typical of the Caryophyllaceous. Traditionally, free central placenta is thought to have evolved from axial placenta by septal disappearance, and axial placenta to have occurred through fusion of conduplicate carpels with marginal placenta. However, the traditional opinion is becoming more and more inconsistent with the new data gained in recent research of angiosperm systematics. To clarify the origin of D. chinensis pistil, the present anatomical study was carried out. The results show that the vascular system of placenta is independent to that of the ovary wall in D. chinensis . Moreover, in the central part of placenta there are one or two amphicribral bundles, and correspondingly numerous ones in the pistil which supply the ovules/seeds. It is obvious that the central amphicribral bundles in placenta are comparable to the counterparts in branches but not to those in leaves or their derivatives. Therefore, it is reasonable to deduce that the placenta of D. chinensis was not derived from conduplicate carpels through fusion of collateral vascular bundles, and actually a floral axis with ovules/seeds laterally adhering. On the contrary, the ovary wall was the lateral appendages of the floral axis. The result of the present study is completely in agreement with Unifying Theory, in which the placenta is taken as an ovule-bearing branch. Except for D. chinensis , the similar vascular organization has been observed in placenta of numerous isolated taxa. But till now, it is uncertain that whether this vascular organization pattern is popular in the whole angiosperms or not. More intensive and extensive investigations are needed.

In this paper, a spoof surface plasmon polarions (SPPs) transmission line is designed by patterning thin metal film in open-cross shape arranged in array. Numerical simulations show the proposed open-cross array can support spoof SPPs with enlarged propagation constant and hence enhanced confinement at metal/dielectric interface as compared to the reported ultra-thin plasmonic waveguide with the rectangular groove or solid-cross. Furthermore, a differential transmission line pair is built with such two close plasmonic arrays. A narrow metal strip locates at the symmetrical plane of the two SPPs waveguides and acts as a resonator to realize common-mode rejection at specific frequency. The notch frequency for common mode can be adjusted by tuning the metal strip length of the resonator while differential mode propagation remains unaffected. Both simulated and experimental results with good agreement are given to verify the proposed idea.

The centromere is responsible for the correct inheritance of eukaryotic chromosomes during cell division. Centromere protein B (CENP‑B) and its 17 base pair binding site (CENP‑B box), which appears at regular intervals in centromeric α-satellite DNA (α-satDNA), are important for the assembly of the centromere components. Therefore, it is conceivable that CENP-B box mutations may induce errors in cell division. However, the association between the deoxynucleotide alterations of the CENP‑B box and the extra chromosome 21 (Chr21) present in patients with Down syndrome (DS) remains to be elucidated. The mutational spectrum of the α‑satDNA, including 4 functional CENP‑B boxes in Chr21 from 127 DS and 100 healthy children were analyzed by direct sequencing. The de novo occurrences of mutations within CENP‑B boxes in patients with DS were excluded. The prevalence of 6 novel mutations (g.661delC, g.1035&#95;1036insA, g.1076&#95;1077insC, g.670T>G, g.1239A>T, g.1343T>C) and 3 single nucleotide polymorphisms (g.727C/T, g.863A/C, g.1264C/G) were not significantly different between DS and controls (P>0.05). However, g.525C/G (P=0.01), g.601T/C (P=0.00000002), g.1279A/G (P=0.002), g.1294C/T (P=0.0006) and g.1302 G/T (P=0.004) were significantly associated with the prevalence of DS (P<0.05). The results indicated that CENP‑B boxes are highly conserved in DS patients and may not be responsible for Chr21 nondisjunction events. However, α‑satDNA in Chr21 is variable and deoxynucleotide deletions, mutations and polymorphisms may act as potential molecular diagnostic markers of DS.

Study Question: Does nm23 have functional significance in decidualization in mice and humans?, Summary Answer: nm23 affects decidualization via the phosphoinositide 3 kinase/mammalian target of rapamycin (PI3K-Akt-mTOR) signaling pathways in mouse endometrial stromal cells (ESCs; mESCs) and human ESCs., What Is Known Already: The function of nm23 in suppressing metastasis has been demonstrated in a variety of cancer types. nm23 also participates in the control of DNA replication and cell proliferation and differentiation., Study Design, Size and Duration: We first analyzed the expression profile of nm23 in mice during early pregnancy (n = 6/group), pseudopregnancy (n = 6/group) and artificial decidualization (n = 6/group) and in humans during the menstrual cycle phases and the first trimester. We then used primary cultured mESCs and a human ESC line, T-HESC, to explore the hormonal regulation of nm23 and the roles of nm23 in in vitro decidualization, and as a possible mediator of downstream PI3K-Akt-mTOR signaling pathways., Participants/materials, Settings and Methods: We evaluated the dynamic expression of nm23 in mice and humans using immunohistochemistry, western blot and real-time quantitative RT-PCR (RT-qPCR). Regulation of nm23 by steroid hormones was investigated in isolated primary mESCs and T-HESCs by western blot. The effect of nm23 knockdown (using siRNA) on ESC proliferation was analyzed by 5-ethynyl-2'-deoxyuridine staining (EdU) and proliferating cell nuclear antigen protein (PCNA) expression. The influence of nm23 expression on the differentiation of ESCs was determined by RT-qPCR using the mouse differentiation markers decidual/trophoblast PRL-related protein (dtprp, also named prl8a2) and prolactin family 3 subfamily c member 1 (prl3c1) and the human differentiation markers insulin-like growth factor binding protein 1 (IGFBP1) and prolactin (PRL). The effects of nm23 siRNA (si-nm23) and the PI3K inhibitor LY294002 on the downstream effects of nm23 on the PI3K-Akt-mTOR signaling pathway were estimated by western blot., Main Results and the Role of Chance: NM23-M1 was specifically expressed in the decidual zone during early pregnancy and in artificially induced deciduoma, and NM23-H1 was strongly expressed in human first trimester decidua. The expression of nm23 was upregulated by oestradiol and progesterone (P < 0.05 versus control) in vitro in mESCs and T-HESC, and this was inhibited by their respective receptor antagonists, ICI 182,780 and RU486. Mouse and human nm23 knockdown decreased ESC proliferation and differentiation (P < 0.05 versus control). The PI3K-Akt-mTOR signaling pathways were downstream mediators of nm23 in mESCs and T-HESCs decidualization., Limitations and Reasons for Caution: Whether the nm23 regulates decidualization via the activation of AMPK, RAS, PKA, STAT3 or other signaling molecules remains to be determined. The role of nm23 in decidualization was tested in vitro only., Wider Implications of the Findings: Results demonstrate that nm23 plays a vital role in decidualization in mice and humans and that nm23 gene expression is hormonally regulated. The downregulation of nm23 in decidua during the first trimester may be associated with infertility in women., Study Funding/competing Interests: This study was supported by the National Natural Science Foundation of China (grant nos. 81370731, 31571551 and 31571190), the Science and Technology Project of Chongqing Education Committee (KJ130309), open funding by the Chongqing Institute for Family Planning (1201) and the Excellent Young Scholars of Chongqing Medical University (CQYQ201302). The authors have no conflicts of interest to declare., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Initiation of apoptosis is an important event for chemoprevention and chemotherapy of cancer. Naturally derived products had drawn growing attention as lead compounds for anticancer drug discovery. ABL-L, a semisynthetic analogue of natural sesquiterpenoid 1-O-acetylbritannilactone (ABL) isolated from Inula britannica, showed stronger suppression against three solid tumor cell lines with 4-10 fold improvement than ABL. However, its molecular mechanism of cell death induction has still not been determined. The present study evaluated the anticancer efficacy of ABL-L and its biological activities mechanism on human laryngocarcinoma cells HEp-2 in vitro. We found that ABL-L-induced inhibition of cell proliferation was associated with an increase in G1-phase arrest. Typical apoptotic morphological and biochemical features were also observed in treated cells. Furthermore, the levels of the anti-apoptotic Bcl-2, pro-caspase 3/8/9 and poly(ADP-ribose) polymerase PARP decreased, and the level of pro-apoptotic Bax increased. Involvement of the caspase-mediated apoptosis was confirmed using caspase inhibitor Z-VAD-FMK pretreatment. In addition, ABL-L induced a tumor suppressor p53 and its target genes expression p21, fas, noxa and puma. The results of p53 knockdown suggest that caspase-mediated apoptosis induced by ABL-L was in p53-dependent pathway on HEp-2 cells. Our data indicate that the cytotoxicity of the novel semisynthetic analogue ABL-L involved G1 cell cycle arrest and apoptosis via a p53-dependent, caspase-mediated pathway on human laryngocarcinoma cells., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Rheumatoid arthritis is an autoimmune disease characterized by synovial hyperplasia and progressive joint destruction. As reported previously, recombinant human endostatin (rhEndostatin) is associated with inhibition of joint bone destruction present in rat adjuvant-induced arthritis; however, the effect of rhEndostatin on bone destruction is not known. This study was designed to assess the inhibitory effect and mechanisms of rhEndostatin on formation and function of osteoclasts in vitro, and to gain insight into the mechanism underlying the inhibitory effect of bone destruction. Bone marrow-derived macrophages isolated from BALB/c mice were stimulated with receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor to establish osteoclast formation. Osteoclast formation was determined by TRAP staining. Cell viability of BMMs affected by rhEndostatin was determined using a MTT assay. Bone resorption was examined with a bone resorption pits assay. The expression of osteoclast-specific markers was analyzed using quantitative real-time PCR. The related signaling pathways were examined using a Luciferase reporter assay and western blot analysis. Indeed, rhEndostatin showed a significant reduction in the number of osteoclast-like cells and early-stage bone resorption. Moreover, molecular analysis demonstrated that rhEndostatin attenuated RANKL-induced NF-κB signaling by inhibiting the phosphorylation of IκBα and NF-κB p65 nuclear translocation. Furthermore, rhEndostatin significantly inhibited the activation of RANKL-dependent mitogen-activated protein kinases, such as ERK1/2, JNK, and p38. Hence, we demonstrated for the first time that preventing the formation and function of osteoclasts is an important anti-bone destruction mechanism of rhEndostatin, which might be useful in the prevention and treatment of bone destruction in RA.

The measurement uncertainty is a non-negative parameter associated with the result of a measurement that characterizes the dispersion of the quantity values that could reasonably be attributed to the measurand. In the present study measurement uncertainty is estimated using the GUM (ISO/IEC Guide 98: 1993 Guide to the expression of uncertainty in measurement) bottom-up approach. The steps were followed: specifying the measurand; identifying all the associated sources of uncertainty; quantifying the uncertainty components; combining the uncertainty components; determining the extended combined standard uncertainty; reviewing the estimates and reporting the measurement uncertainty. In this process, the major uncertainty components with greater impact were identified; try to eliminate or to reduce the impact of these components can improve measurement methods. Examples were the determination of aluminum in starch and bread crumbs by inductively coupled plasma-mass spectrometry (ICP-MS). The uncertainties of aluminum contents were from measurement repeatability, variability of calibration curve, standard stock solution, dilution, solution volume and sample weighing. The data indicated that the major contributions to the uncertainty budget originating from urel(cAl)1 (the relative standard uncertainty of aluminum content derived from linear least squares calibration), urel(cAl)3 (the relative standard uncertainty of aluminum content derived from the dilution of the standard stock solutions) and urel(rep) (the relative standard uncertainty derived from the repeatability). Based on the analysis of the main individual contributions of each uncertainty source to the total uncertainty value, several modifications were proposed. Firstly helium collision mode was replaced by no gas mode to improve the sensitivity of mass spectrometry. Secondly the number of measurements was increased. Thirdly let the mean of data points in the calibration closer the measurand. Finally the relative error smaller gauges were used. After these modifications, urel(cAl)1, urel(cAl)3 and urel(rep) were from (0.035 8, 0.013 2, 0.008 5) down to (0.006 0, 0.010 5, 0.003 3), respectively; the combined relative standard uncertainty of aluminum was from 0.039 down to 0.013; the expanded uncertainty from 1.8 down to 0.4 mg·kg-1(coverage factor k=2). The improvement effect was significant.

It is well known that maternal folate deficiency results in adverse pregnancy outcomes. In addition to aspects in embryonic development, maternal uterine receptivity and the decidualization of stromal cells is also very important for a successful pregnancy. In this study, we focused on endometrium decidualization and investigated whether apoptosis, which is essential for decidualization, was impaired. Flow cytometry and TUNEL detection revealed that apoptosis of mouse endometrium decidual cells was suppressed in the dietary folate-deficient group on Days 7 and 8 of pregnancy (Day 1 = vaginal plug) when decidua regression is initiated. The endometrium decidual tissue of the folate deficiency group expressed less Bax compared to the normal diet group while they had nearly equal expression of Bcl2 protein. Further examination revealed that the mitochondrial transmembrane potential (ΔΨm) decreased, and the fluorescence of diffuse cytoplasmic cytochrome c protein was detected using laser confocal microscopy in normal decidual cells. However, no corresponding changes were observed in the folate-deficient group. Western blotting analyses confirmed that more cytochrome c was released from mitochondria in normal decidual cells. Taken together, these results demonstrated that folate deficiency could inhibit apoptosis of decidual cells via the mitochondrial apoptosis pathway, thereby restraining decidualization of the endometrium and further impairing pregnancy.

Activin is a multifunctional growth and differentiation factor of the growth factor-beta (TGF-β) superfamily, which inhibits the proliferation of colon cancer cells. It induces phosphorylation of intracellular signaling molecules (Smads) by interacting with its type I and type II receptors. Previous studies showed that human activin receptor-interacting protein 2 (hARIP2) can reduce activin signaling by interacting with activin type II receptors; however, the activity of hARIP2 in colon cancer has yet to be detailed. In vitro, overexpression of hARIP2 reduced activin-induced transcriptional activity and enhanced cell proliferation and colony formation in human colon cancer HCT8 cells and SW620 cells. Also, hARIP2 promoted colon cancer cell apoptosis, suggesting that a vital role in the initial stage of colon carcinogenesis. In vivo, immunohistochemistry revealed that hARIP2 was expressed more frequently and much more intensely in malignant colon tissues than in controls. These results indicate that hARIP2 is involved in human colon tumorigenesis and could be a predictive maker for colon carcinoma aggressiveness.

Kiwi fruit is of great agricultural, botanical, and economic interest. The flower of kiwi fruit has axile placentation, which is typical for Actinidiaceae. Axile placentation is thought derived through fusion of conduplicate carpels with marginal placentation according to the traditional doctrine. Recent progress in angiosperm systematics has refuted this traditional doctrine and placed ANITA clade rather than Magnoliaceae as the basalmost clade. However, the former traditional doctrine stays in the classrooms as the only teachable theory for the origin of carpels. To test the validity of this doctrine, we performed anatomical study on kiwi fruit. Our study indicates that the placenta has a vascular system independent of that of the ovary wall, the ovules/seeds are attached to the placenta that is a continuation of floral axis enclosed by the lateral appendages that constitute the ovary wall, and there are some amphicribral bundles in the center of placenta and numerous amphicribral bundles supplying ovules/seeds in kiwi fruit. The amphicribral vascular bundles supplying the ovules/seeds are comparable to those usually seen in branches, but not comparable to those seen in leaves or their derivatives. This comparison indicates that the placenta in kiwi fruit cannot be derived from the fusion of collateral ventral bundles of conduplicate carpels, as suggested by traditional doctrine. Instead the vascular organization in placenta of kiwi suggests that the placenta is a shoot apex-bearing ovules/seeds laterally. This conclusion is in line with the recently raised Unifying Theory, in which the placenta is taken as an ovule-bearing branch independent of the ovary wall (carpel in strict sense). Similar vascular organization in placenta has been seen in numerous isolated taxa besides kiwi fruit. Therefore whether such a pattern is applicable for other angiosperms is an interesting question awaiting answering.

Background: The lack of an accurate noninvasive method for assessing right ventricular (RV) volume and function has been a major deficiency of two-dimensional (2D) echocardiography. The aim of our study was to test the feasibility of single-beat full-volume capture with real-time three-dimensional echo (3DE) imaging system for the evaluation of RV volumes and function validated by cardiac magnetic resonance imaging (CMRI)., Methods: Sixty-one subjects (16 normal subjects, 20 patients with hypertension, 16 patients with pulmonary heart disease and 9 patients with coronary heart disease) were studied. RV volume and function assessments using 3DE were compared with manual tracing with CMRI as the reference method., Results: Fifty-nine of 61 patients (96.7%; 36 male, mean age, 62 ± 15 years) had adequate three-dimensional echocardiographic data sets for analysis. The mean RV end diastolic volume (EDV) was 105 ± 38 ml, end-systolic volume (ESV) was 60 ± 30 and RV ejection fraction (EF) was 44 ± 11% by CMRI; and EDV 103 ± 38 ml, ESV 60 ± 28 ml and RV EF 41 ± 13% by 3DE. The correlations and agreements between measurements estimated by two methods were acceptable., Conclusion: RV volumes and function can be analyzed with 3DE software in most of subjects with or without heart diseases, which is able to be estimated with single-beat full-volume capture with real-time 3DE compared with CMRI., (© 2013.)

IgG4-related disease (IgG4-RD) is a novel and rare autoimmune disease entity. Elevated serum IgG4 level is strongly suggestive of IgG4-RD. But it is still unknown whether serum IgG4 elevation commonly occurs in other autoimmune diseases. In this study, the serum IgG4 levels were detected by an established enzyme-linked immunosorbent assay (ELISA) in a variety of autoimmune diseases including systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), polymyositis or dermatomyositis (PM/DM) and IgG4-RD. To evaluate the reliability of this ELISA system, some of our samples were sent to a lab in Kanazawa Medical University, Japan, and detected by using the nephelometric assay. The results showed that our findings were consistent with theirs. Moreover, it was found that the serum IgG4 levels were 0.23±0.16 g/L in 53 healthy controls, 0.16±0.15 g/L in 103 SLE patients, 0.22±0.18 g/L in 41 SS patients and 0.40±0.32 g/L in 21 PM/DM patients. No significant difference in the serum IgG4 level was observed among these groups (P>0.05). The serum IgG4 levels of two cases of IgG4-RD were 1.63 and 4.65 g/L respectively, and both decreased markedly after treatment with glucocorticoids. These data indicated that this established ELISA system can be used for detecting serum IgG4 levels. Elevated serum IgG4 levels help diagnose IgG4-RD and evaluate the curative effect of this condition rather than other autoimmune diseases.

Objective: To assess the relationship between folate biomarkers levels and IGF2 imprinting status among second trimester pregnant Chinese women., Study Design: Three hundred women in their second trimester were screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for analysis of IGF2 imprinting status. Statistical differences of folate biomarkers levels were calculated in the groups with different imprinting status., Results: Of the 300 women analyzed, 133 (44.33%) cases were homozygous allele with A, 3 (1.00%) cases were homozygous allele with G, while 164 (54.67%) cases were heterozygous with A and G, qualifying them for analysis of loss of imprinting (LOI). Among the 164 cases undergoing LOI analysis, 44 (26.83%) were IGF2 LOI cases, while 120 (73.17%) were IGF2 retention of imprinting (ROI) ones. The mean level of serum folate, vitamin B12 and tHcy was 28.46 +/- 10.74 ng/mL, 380.20 +/- 206.13 pg/mL, 14.24 +/- 6.34 micromol/L among women with IGF2 ROI, and 30.89 +/- 9.97 ng/mL, 394.28 +/- 195.92 pg/ mL, and 13.12 +/- 6.23 micromol/L among women with IGF2 LOI, respectively., Conclusion: No significant difference of folate biomarkers levels was observed between IGF2 ROI and IGF2 LOI groups.

Calreticulin (CRT), a Ca(2+)-binding storage protein and chaperone in the endoplasmic reticulum, modulates cell adhesiveness and integrin-dependent Ca(2+) signaling. However, the role of CRT during implantation remains poorly understood. In the present study, we characterized the expression of CRT mRNA and the protein in mouse endometria from pregnancy DI to D7. Real-Time PCR and in situ hybridization results showed that the levels of CRT mRNA in the endometria of pregnant mice were significantly higher than those of non-pregnant mice (P<0.05), and increased gradually from pregnancy DI to D4, reaching the máximum level on D4, followed by a plateau from D4 to D7. Using immunofluorescence histochemistry and western blot, changes of CRT expression in the endometria of pregnant mice were consistent with the expression of CRT mRNA. Furthermore, antisense CRT oligodeoxynucleotide was injected into the uterus horns of pregnant mice (D3) to investígate its effect on embryo implantation. The result showed that the number of implanted embryos markedly decreased in the side of uterine horns receiving antisense CRT oligodeoxynucleotide(í(>)<0.05). These findings suggest that CRT may play an important role in embryo implantation in mice.

Selective microelectrode technique, known as an electrophysiological approach, can be used to measure directly specific information on ion or molecule distribution and movement both inside and outside of living organelle, biological cells, tissue and organs. It has several advantages over other methods in measuring ionic or molecular information, e.g. easy to handle, fast response, high sensitivity (10(-12) moles cm(-2) s(-1)) and non-invasive to the samples in addition to continuous measurement and automatic monitoring. Microscopic-scale selective electrode (with a tip diameter of 0.5-5 microm) can be used to measure net fluxes of ions or molecules outside of growing biological cells, tissues and organs, to measure activities of ions or molecules inside of growing organelle and biological cells. Thus, it has many applications in various research fields. The technical principle of design and use of selective microelectrode and its progress and development prospect in plant physiological research are summarized.

Objective: To investigate the changes of spontaneous and cognitive behavior, and cholinergic M receptors in the brain of mice subjected to chronic mild stress (CMS), and to determine the effect of Ning Shen Ling Granule (NSL) and dehydroepiandrosterone (DHEA) on them., Methods: CMS model mice were established by applying stress every day for 3 consecutive weeks with 7 kinds of unforeseeable stress sources, and they were medicated for 1 week beginning at the 3rd week of modeling. The changes in behavior were determined by Morris Water Maze and spontaneous movement test, and M-receptor binding activity in cerebral cortex, hippocampus and hypothalamus were measured by radioactive ligand assay with 3H-QNB., Results: (1) The spontaneous movement in CMS model mice was significantly reduced, with the latency for searching platform in Morris Water Maze obviously prolonged (P<0.01), and these abnormal changes in behavior were improved in those treated with NSL and DHEA. (2) The binding ability of M-receptor in cerebral cortex and hippocampus of CMS mice was significantly decreased as compared with those in the control group (P<0.05), but could be restored to the normal level after intervention with NSL or DHEA., Conclusion: The decline of spontaneous movement and spatial learning and memory ability could be induced in animals by chronic mild stress, and that may be related to the low activity of central cholinergic M-receptors. Both NSL and DHEA could effectively alleviate the above-mentioned changes.

With lower-and higher heat-resistant varieties of eggplant (Solanum melongena L.) Heibei I and Heibei II as test materials, and by using Plant Efficiency Analyzer (PEA) from Hansatech, this paper measured the fast chlorophyll a fluorescence transient and its parameters. The results showed that PS II construction became more sensitive to heat stress when ambient temperature was higher than 40 degrees C. The F0 went up slowly, and Fv/Fm and deltaF/Fm' came down dramatically. Heibei II had a longer semi-attenuation temperature of Fv/Fm (T50) and deltaF/Fm' (t50) than Heibei I. Under strong heat stress (5 min at 48 degrees C or 20-30 min at 44 degrees C), the K-step in relation to the inactivation of oxygen-evolving complex appeared in fluorescence rise at about 700 micros, and the regular O-J-I-P transient was transformed to O-K-J-I-P one. The K-phase of Heibei I and Heibei II appeared when the treatment time was up to 20 and 30 minutes at 44 degrees C, respectively. In comparing with 35 degrees C heat treatment, the DI0/RC in the parameters of Strasser's specific energy fluxes model was increased by a great extent under 48 degrees C or more heat stress, reflecting a strong safeguard of energy dissipation to PS II. When the temperature of heat stress increased from 35 degrees C to 52 degrees C, the Fvi/Fv of PS II silent reaction centers of Heibei I and Heibei II increased remarkably.

AIM:To observe the therapeutic effect of Wei-xibaonizhuan pills on gastric precancerous lesions.METHODS: Thirty patients with gastric precancerous lesions were treated with Weixibaonizhuan pills for 3 months. Of the 36 cases, 13 (36.1%) were mild atrophic gastritis, 14 (38.9%) moderate atrophic gastritis and 9 (25.0%) severe atrophic gastritis; among them 22 (61.1%) and 27 cases (75.0%) were accompanied with intestinal metaplasia (IM) and dysplasia (DYS) respectively. Of the 36 patients, 20 were men and 16 women, aged from 30-60 years and those aged 30-59 years accounted for 61.1%. The course of disease ranged from 3 months to 21 years, and 20 (55.6%) of them had a course of 5-10 years. The clinical manifestations were fullness of the abdomen (31 cases),abdominalgia (27 cases), anorexia (30 cases), gas eructation (26 cases), acid regurgitation (6 cases) and loose stool (9 cases). When treatment ended, the improvement of patients' clinical symptoms, atrophy of gastric mucosa, IM and DYS were analysed.RESULTS: After 3 months' treatment with Wei-xibaonizhuan pills,7 cases recovered, 11 cases were much improved, 13 cases showed some improvement, and 5 cases were ineffective; the total rate of symptomatic improvement was 86.1%. Of the 13 cases with mild atrophic gastritis, 11 cases changed into superficial gastritis, and 2 cases had no changes. Of the 14 cases of moderate atrophic gastritis, 4 cases changed into superficial gastritis, 7 cases changed into mild atrophic gastritis, and 3 cases had no changes. Five of 9 cases of severe atrophic gastritis were reduced to moderate atrophic gastritis, and 4 cases had no changes. The total effective rate was 77.8% in chronic atrophic gastritis. Of the 9 cases with mild IM, IM disappeared in 6 cases and 3 showed no change. Of the 10 cases with moderate IM, it disappeared in 2 cases, 5 cases changed to ild IM, and 3 cases had no change. One of the 4 cases of severe IM changed to moderate IM and 3 had no change. The total effective rate was 63.6% in IM. Of the 16 cases of mild DYS, 11 cases showed disappearance of DYS and 5 had no change. In 9 cases of moderate DYS, 2 showed disappearance, 5 changed to mild DYS and 2 had no change. Two cases of severe DYS, both showed no change. The total effective rate was 66.7% in DYS. Before treatment, the I, II, III and IV degree positive expressions of CEA were present in 13, 12, 9 and 2 cases, respectively, whereas after treatment, the positive expressions were present in 25, 7, 3 and 1, respectively. Before treatment, the I, II, III and IV degree positive expressions of PCNA were present in 16, 11, 10 and 4 respectively, but after treatment, they were present in 21, 9, 5 and 1 respectively. In short, the positive expressions of CEA and PCNA of gastric mucosa were significantly decreased after treatment (P < 0.01).CONCLUSION: Weixibaonizhuan pill has a therapeutic effect in gastric precancerous lesions.

Aim: To study the therapeutic effect of Weixibaonizhuanwan on gastric precancerous lesions., Methods: Thirty-six patients with gastric precancerous lesions were treated with Weixibaonizhuanwan for 3 mo. Thirteen (36.1%) patients presented with mild atrophic gastritis, 14 (38.9%) with moderate atrophic gastritis, and nine (25.0%) with severe atrophic gastritis. Twenty-two (61.1%) and 27 (75.0%) of the cases were accompanied by intestinal metaplasia (IM) and dysplasia (DYS), respectively. Twenty of the 36 patients were men and 16 were women, ranging from 30 to 67 years in age, with 61.1% of the patients being 40-59 years old. The duration of the disease in these patients ranged from 3 mo to 21 years, with 20 (55.6%) patients experiencing durations of the disease between 5 and 10 years. The clinical manifestations of the disease in these patients included fullness of the abdomen (31 cases), abdominalgia (27 cases), anorexia (30 cases), eructation (26 cases), pantothenic acid (6 cases), and loose stool (9 cases). Patients were treated with Weixibaonizhuanwan and symptom improvement, level of atrophy of the gastric mucosa, and IM and DYS progression were analyzed., Results: After a 3-mo treatment with Weixibaonizhuanwan, seven patients experienced recovery. The treatment was effective in 11 cases, improved symptoms in 13 cases, and was ineffective in five cases. The overall efficacy rate was 86.1%. In patients with mild atrophic gastritis (n = 13), 11 improved into superficial gastritis and two experienced no improvement. In 14 cases of moderate gastritis, four cases improved into superficial gastritis and seven turned into mild atrophic gastritis, with three patients experiencing no improvement. Among severe atrophic gastritis patients (n = 9), five improved into moderate atrophic gastritis after treatment and four experienced no improvement. The overall efficacy rate in chronic atrophic gastritis patients was 77.8%. Among 9 patients with IM, IM disappeared in six cases, whereas three cases showed no improvement after treatment. In cases with moderate IM (n = 10), IM disappeared in two, turned into mild IM in five, and showed no change in three. Out of four cases with IM, one case turned into moderate IM and three showed no change. The overall efficacy rate in IM patients was 63.6%. Out of 16 cases of mild DYS, DYS disappeared in 11, whereas five cases showed no change. Out of nine cases of moderate DYS, DYS disappeared in two and turned into mild DYS in five cases, with two patients experiencing no change after treatment. No improvement was observed in the two cases of severe DYS after treatment. The overall efficacy rate in DYS patients was 66.7%. After treatment, expression of carcinoembryonic antigen (CEA) and proliferating cell nuclear antigen (PCNA) in gastric mucosa significantly decreased (P < 0.01). Before treatment, cancer staging of these patients by positive CEA expression was I, II, III, and IV in 13, 12, 9, and 2 cases, respectively. After treatment, the number of cases per stage changed to 25, 7, 3, and 1, respectively. Similarly, before treatment, staging by positivity of PCNA expression was I, II, III, and IV in 16, 11, 10, and 4 cases, respectively, and changed to 21, 9, 5, and 1, respectively, after treatment., Conclusion: The use of Weixibaonizhuanwan in the treatment of gastric precancerous lesions showed promising therapeutic effects in patients after 3-mo treatments.