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DNA modifications add another layer of complexity to the eukaryotic genome to regulate gene expression, playing critical roles as epigenetic marks. In eukaryotes, the study of DNA epigenetic modifications has been confined to 5mC and its derivatives for decades. However, rapid developing approaches have witnessed the expansion of DNA modification reservoirs during the past several years, including the identification of 6mA, 5gmC, 4mC, and 4acC in diverse organisms. However, whether these DNA modifications function as epigenetic marks requires careful consideration. In this review, we try to present a panorama of all the DNA epigenetic modifications in eukaryotes, emphasizing recent breakthroughs in the identification of novel DNA modifications. The characterization of their roles in transcriptional regulation as potential epigenetic marks is summarized. More importantly, the pathways for generating or eliminating these DNA modifications, as well as the proteins involved are comprehensively dissected. Furthermore, we briefly discuss the potential challenges and perspectives, which should be taken into account while investigating novel DNA modifications., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Lung squamous cell carcinoma (LUSC) is associated with a low survival rate. Evidence suggests that bone morphogenetic proteins (BMPs) and their receptors (BMPRs) play crucial roles in tumorigenesis and progression. However, a comprehensive analysis of their role in LUSC is lacking. Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC., Methods: The "R/Limma" package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC, using data from TCGA, GTEx, and GEO databases. Concurrently, the "survminer" packages were employed to investigate their prognostic value and correlation with clinical features in LUSC. The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis (WGCNA). LASSO analysis was conducted to construct a prognostic risk model for LUSC. Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC. Furthermore, based on the tumor immune estimation resource database and tumor-immune system interaction database, the role of the core gene in the tumor microenvironment of LUSC was explored., Results: GDF10 had a significant correlation only with the pathological T stage of LUSC, and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC. A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes (HRASLS, HIST1H2BH, FLRT3, CHEK2, and ALPL) for LUSC. GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression., Conclusion: GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC., (© 2024. Huazhong University of Science and Technology.)

Background and Objectives: To assess the vitamin D nutritional status (VDN) of pregnant women in early pregnancy and investigate the effects of periconceptional supplementation with multiple micronutrients (MMs) on this status., Methods and Study Design: Data were taken from the Pregnancy Health Care System and Hospital Information System in 2018 in Beijing. Vitamin D nutritional status in early pregnancy was evaluated among 4,978 pregnant women, and 4,540 women who took folic acid only (FA) or multiple mi-cronutrients supplements (MM) during the periconceptional period, were include to estimate the associations between periconceptional supplementation with MM and prevalence of vitamin D deficiency or insufficiency with logistic regression model., Results: The mean early-pregnancy vitamin D concentration was 18.6 (±7.5) ng/mL, and the rates of deficiency and insufficiency were 31.6% and 60.5%, respectively. Compared to the FA group, the adjusted odds ratio (aOR, 95%confidence interval, CI) for insufficiency or deficiency of the MM group were 0.25(0.18-0.34), and the aOR (95%CI) for deficiency of the MM group were 0.17 (0.12-0.23). Women who took MMs for a longer period of time, at higher frequencies, and with higher compliance scores had lower rates of deficiency and insufficiency. In winter, spring, and autumn, taking MMs could reduce deficiency by about 70%; in summer, there was little effect., Conclusions: Among women in Beijing, serum concentrations of vitamin D in early pregnancy are relatively low, and the rates of deficiency and insufficiency are high. Taking MMs during the periconceptional period could improve this situation., Competing Interests: The authors declare that there are no conflicts of interest exist in relation to the publication of this paper

Objectives: The purpose of this study was to develop a novel Bonwill⁃Hawley method (Bonwill⁃Hawley arch form based on CBCT image) for the assessment of dental crowding, and to investigate and compare the accuracy and eligibility with the conventional brass wire and caliper methods under different crowding conditions., Material and Methods: Sixty patients with the pair of plaster casts and CBCT data were collected. All the casts were marked and transformed into digital models using iTero scanner, and imported into OrthoCAD software to measure the required space. Using the conventional brass wire (M1) and caliper methods (M2), the available space and dental crowding were measured and calculated basing on digital models, respectively. Correspondingly, the axial planes in the level of dental arches were oriented and captured from the CBCT images to draw the Bonwill⁃Hawley arch forms (M3), which were used to measure and calculate the available space and dental crowding. For each method, intra and inter-examiner reliabilities were evaluated with intra-class correlation coefficients (ICCs). Wilcoxon test and Kruskal-Wallis test were performed for statistically analyzing the discrepancy among different groups., Results: Both intra- and inter-examiner reliability were generally excellent for all parameters obtained by the three methods, except for the dental crowding measured using M1(ICC: 0.473/0.261). The dental crowding measured using M2 were significantly increased in mild, moderate and severe-crowding groups compared with M1. However, no significant difference was detected between M1 and M3 in severe-crowding group (maxilla, p = 0.108 > 0.05; mandible, p = 0.074 > 0.05). With the deterioration of crowding condition, the discrepancy of dental crowding between M1 and M2, or M1 and M3 were significantly decreased (maxilla, M2-M1, mild VS serve, p = 0.003 < 0.05; maxilla, M3-M1, mild VS serve, p = 0.003 < 0.05; mandible, M2-M1, mild VS serve, p = 0.000 < 0.001; mandible, M3-M1, mild VS serve, p = 0.043 < 0.05)., Conclusion: Dental crowding measured using the novel Bonwill⁃Hawley method was relatively greater than the caliper method, but not exceeding the brass wire method, which wound gradually come close to the brass wire method with the deterioration of crowding condition., Clinical Relevance: The Bonwill⁃Hawley method basing on CBCT image proved to be a reliable and acceptable choice for orthodontists to analyze the dental crowding., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To explore the association between periconceptional supplementation of folic acid or multiple-micronutrients containing folic acid(MMFA) and risk of preterm delivery in women with natural conception, singleton pregnancy and vaginal delivery., Methods: A retrospective cohort study was performed based on the prenatal health care system and hospital information system of Tongzhou Maternal and Child Health Hospital of Beijing and the women who had their prenatal care in the hospital from January 2015 to December 2018 were included. The information of 16 332 women who conceived naturally, had a singleton pregnancy, and delivered vaginally was collected. Compliance scores were constructed based on the time of initiation and the frequency of taking nutritional supplements. The association between maternal periconceptional micronutrient supplementation, including pure folic acid (FA) pills or MMFA and the rate of preterm delivery was evaluated using Logistic regression models., Results: The preterm delivery rate (gestational week < 37 weeks) of the study population was 3.8%, and the mean (standard deviation) of gestational age was (38.98±1.37) weeks. A total of 6 174 (37.8%) women took FA during the periconceptional period, 8 646 (52.9%) women took MMFA, and 1 512 (9.3%) women did not take any nutritional supplements. The association between periconceptional supplementation of FA or MMFA and risk of preterm delivery in women was not statistically significant [adjusted odds ratio (a OR )=1.01, 95% CI : 0.74-1.37]. The associations with preterm birth were not statistically significant in further analysis by the type of nutritional supplements, time of initiation, and the frequency of supplementation. In addition, the association between the compliance score of taking supplements and the rate of preterm delivery was not statistically significant, either., Conclusion: This study did not find an association between the risk of preterm delivery and the use of FA or MMFA during the periconcep-tional period in women with natural conception, singleton pregnancy, and vaginal delivery. In the future, multicenter studies with large-scale prospective cohort or population-based randomized controlled trials are warranted to confirm the association between taking FA or MMFA during the periconceptional period and preterm delivery among women.

Esophageal cancer (ESCA) is a lethal malignancy and is associated with the alterations of various genes and epigenetic modifications. The protein dpy-30 homolog (DPY30) is a core member of histone H3K4 methylation catalase and its dysfunction is associated with the occurrence and development of cancer. Therefore, the present study investigated the role of DPY30 in ESCA and evaluated the association between the expression of DPY30, the clinicopathological characteristics of ESCA and the tumor immune microenvironment. It conducted a comprehensive analysis of DPY30 in patients with ESCA using The Cancer Genome Atlas (TCGA) database and clinical tissue microarray specimens of ESCA. Immunohistochemistry was performed to assess the expression levels of DPY30 in tissues. Receiver operating curve analysis, Kaplan-Meier survival analysis and Cox regression analysis were performed to identify the diagnostic and prognostic value of DPY30. Gene Set Enrichment Analysis, protein-protein interaction network and Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression data were used to screen DPY30-associated genes and evaluate the immune score of the TCGA samples. The results demonstrated that the expression of mRNA and protein levels of DPY30 were significantly upregulated in tumor tissues compared with normal tissue samples. The expression of DPY30 was closely associated with the poor prognosis of patients with ESCA. The present study also found that DPY30 expression and the pathological characteristics of ESCA were significantly correlated. Additionally, the expression of DPY30 demonstrated a significant positive correlation with various immune cells infiltration. The results suggested that DPY30 might influence tumor immune infiltration. In conclusion, the findings suggested that DPY30 might be a potential prognostic biomarker and an immunotherapeutic target in ESCA., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Mei et al.)

Background: Patients with unilateral cleft lip and palate were associated with different nasomaxillary complex from the normal population. Although the biomechanical effects of conventional rapid palatal expansion (Hyrax expansion) and bone-borne rapid palatal expansion (micro-implant-assisted expansion) in non-cleft patients have been identified by multiple studies, little is known in patients with unilateral cleft lip and palate. The purpose of this study was to investigate and compare the biomechanical effects of the conventional and bone-borne palatal expanders in a late adolescence with unilateral cleft lip and palate., Methods: A cone beam CT scan of a late adolescence with unilateral cleft lip and palate was selected to construct the three-dimensional finite element models of teeth and craniofacial structures. The models of conventional and born-borne palatal expanders were established to simulate the clinical maxillary expansion. The geometric nonlinear theory was applied to evaluate the Von Mises stress distribution and displacements in craniofacial structures and teeth., Results: Bone-borne palatal expander achieved more transverse movement than conventional palatal expander in the whole mount of craniofacial regions, and the maximum amount of expansion was occurred anteriorly along the alveolar ridge on cleft-side. The expanding force from born-borne palatal expander resulted in more advancement in nasomaxillary complex than it in conventional palatal expander, especially in the anterior area of the minor segment of maxilla. Stresses from the both expanders distributed in similar patterns, but larger magnitudes and ranges were generated using the bone-borne expander around the maxillary buttresses and pterygoid plates of sphenoid bone. The maximum expanding stresses from born-borne palatal expander were concentrated on palatal slope supporting minscrews, whereas those from conventional palatal expander were concentrated on the anchoring molars. In addition, the buccal tipping effect of teeth generated using the bone-borne expander was less than it using the conventional palatal expander., Conclusion: Bone-borne expander generated enhanced skeletal expansion at the levels of alveolar and palate in transversal direction, where the miniscrews contributed increased expanding forces to maxillary buttresses and decreased forces to buccal alveolar. Bone-borne expanders presented a superiority in correcting the asymmetric maxilla without surgical assistant in late adolescence with unilateral cleft lip and palate., (© 2022. The Author(s).)

Pleural effusion (PE) is a common manifestation of tuberculosis (TB) and malignant tumors but tuberculous PE (TPE) is difficult to distinguish from malignant PE (MPE), especially by noninvasive detection indicators. This study aimed to find effective detection indices in blood and PE for differentiating TB from a malignant tumor. A total of 815 patients who were diagnosed with TB or cancer in Hubei Shiyan Taihe Hospital from 2014 to 2017 were collected. Amongst them, 717 were found to have PE by thoracoscopy. Clinical characteristics, patients' blood parameters and PE indicator information were summarized for analysis. Patients with MPE had higher percentages to be bloody and negative of Rivalta test in PE than those with TPE. For clinical indicators, comparison of the specific parameters in blood showed that 18 indicators were higher in the TPE group than in the MPE group. By contrast, 12 indicators were higher in the MPE group than in the TPE group (P < .01). In addition, in PE tests, 3 parameters were higher in the TPE group, whereas other 4 parameters were higher in the MPE group (P < .01). Then, for clinical diagnosing practice, ROC analysis and principal component analysis were applied. The top 6 relevant indicators with area under curve over 0.70 were screened out as follows: hydrothorax adenosine dehydrogenase (pADA, 0.90), hydrothorax high-sensitivity C reactive protein (0.79), percentage of blood monocyte (sMONp, 0.75), blood high-sensitivity C reactive protein (sHsCRP, 0.73), erythrocyte sedimentation rate (0.71) and blood D-dimer (0.70). Moreover, logistic regression model revealed that a specific combination of 3 biomarkers, namely, pADA, sMONp and sHsCRP, could enhance the distinguishment of TB from malignant tumor with PE (area under curve = 0.944, 95% confidence interval = 0.925-0.964). The diagnostic function of the top single marker pADA in patients from different groups was analyzed and it was found to maintain high specificity and sensitivity. The 6 indicators, namely, pADA, hydrothorax high-sensitivity C reactive protein, sMONp, sHsCRP, sESR and blood D-dimer, showed significant diagnostic value for clinicians. Further, the combination of pADA, sMONp and sHsCRP has high accuracy for differential diagnosis for the first time. Most interestingly, the single marker pADA maintained high specificity and sensitivity in patients with different statuses and thus has great value for rapid and accurate diagnosis of suspected cases., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Research on the mechanism of plant root-soil consolidation is a current focus in research into the ecological restoration of banks. The stability of ecological banks is central to this research, and bank stability is closely related to plant combinations and spacing. Recent research on reinforced anchorage of plant roots has mainly focused on root length and angle, and on other parts of the root system, and only a few studies have examined the combination of different types of roots. In this study, a coupled slope stability assessment system is created, composed of root morphological parameters and involving calculations using the finite element model ABACUS. This paper selects the two banks of the lower reaches of the Tiantang River in the flood zone of Yongding River as the research area, and examines slope surface plants. And then the reinforcement effect of different shrub roots combinations and plant spacing are evaluated for determining the optimal shrub layout, with the aim of solving the instability problem of collapsible silty clay bank slopes and associated risks. The results indicated that when the shrub plant spacing is 0.65 m, the optimal shrub combination is Tamarix chinensis + Philadelphus incanus, and when the shrub plant spacing is 0.75 m, the optimal shrub combination is Tamarix chinensis + Euonymus alatus. The study found that the root system morphology and the fibrous roots amount at the foot of the slope can have different degrees of influence on the shallow soil stability of the silty clay slope under different shrubs plant spacing conditions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Biologically active sphingolipids are closely related to the growth, differentiation, aging, and apoptosis of cancer cells. Some sphingolipids, such as ceramides, are favorable metabolites in the sphingolipid metabolic pathway, usually mediating antiproliferative responses, through inhibiting cancer cell growth and migration, as well as inducing autophagy and apoptosis. However, other sphingolipids, such as S1P, play the opposite role, which induces cancer cell transformation, migration and growth and promotes drug resistance. There are also other sphingolipids, as well as enzymes, played potentially critical roles in cancer physiology and therapeutics. This review aimed to explore the important roles of sphingolipid metabolism in cancer. In this article, we summarized the role and value of sphingolipid metabolism in cancer, including the distribution of sphingolipids, the functions, and their relevance to cancer diagnosis and prognosis. We also summarized the known and potential antitumor targets present in sphingolipid metabolism, analyzed the correlation between sphingolipid metabolism and tumor immunity, and summarize the antitumor effects of natural compounds based on sphingolipids. Through the analysis and summary of sphingolipid antitumor therapeutic targets and immune correlation, we aim to provide ideas for the development of new antitumor drugs, exploration of new therapeutic means for tumors, and study of immunotherapy resistance mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Wang, Wang, Xie, Wang, Pan, Meng, Liang, Li, Yan, Wu, Liu, Yao and Leung.)

Objective: To explore the association of maternal periconceptional folic acid or multiple micronutrients supplementation during periconceptional period and the serum vitamin E (Vit.E) concentration in the 1st trimester of gestational period., Methods: A retrospective cohort study was conducted based on the prenatal health care system and clinical laboratory information system. Totally, 22 171 pregnant women who had their prenatal health care and gave birth in Tongzhou Maternal & Child Health Hospital of Beijing from Jan. 2016 to Dec. 2018 were recruited. The usage patterns of nutritional supplements [folic acid (FA) or multiple micronutrients (MM)] during periconceptional period were independent variables, and serum Vit.E concentration and serum Vit.E concentration≥11.2 mg/L in the 1st trimester of gestational period were outcome variables for generalized linear regression model and Logistic regression model, respectively, to analyze the relationships between the independent and outcome variables., Results: The range of the serum Vit.E concentration in the 1st trimester of gestational period was 5.2-24.0 mg/L, and the median concentration was 10.1 (8.8-11.6) mg/L; the excess rate of the serum Vit.E of those who took MM supplementation was 0.3%, and the rates for the groups of FA only or no nutritional supplements used were both 0.1%. Compared with women without nutritional supplement or the women taking FA, the women who took MM had higher serum Vit.E levels in the 1st trimester of gestational period (both P < 0.05). The women taking FA or MM initiated before the conception showed that the serum Vit.E concentration in the 1st trimester of gestational period was higher than that after the conception ( P < 0.05), and the serum Vit.E concentration of women who took regularly was higher than that of irregular taking ( P < 0.05); with taking compliance elevated, the serum Vit.E concentration of the two groups of women taking FA or MM increased ( P < 0.05). The risk of serum Vit.E concentration≥11.2 mg/L among the women taking MM was higher than that of the women without nutritional supplements or taking FA only [odds ratio ( OR )=1.36, 95% confidence interval (95% CI ): 1.21-1.53; OR =1.39, 95% CI : 1.31-1.48)]; women who took FA or MM showed a lower risk for serum Vit.E concentration≥11.2 mg/L of taking it after the conception than before, the ORs (95% CI ) were 0.86 (95% CI : 0.77-0.96) and 0.88 (95% CI : 0.81-0.95), respectively; the women taking the two supplements regularly had higher risk for serum Vit.E concentration≥11.2 mg/L than irregular taking, the ORs (95% CI ) were 1.16 (95% CI : 1.05-1.29) and 1.13 (95% CI : 1.04-1.22) for FA and MM users, respectively; with the compliance increasing, the women taking MM had a higher risk of serum Vit.E levels≥11.2 mg/L in the 1st trimester [ OR (95% CI ) was 1.10 (1.07-1.14)], but for FA users, the OR (95% CI ) was 1.04(1.00-1.08)., Conclusion: Vit.E nutritional status in women in early gestational period in Beijing was generally good, and the excess rate of serum Vit.E was higher in women who took MM during periconceptional period than those without nutritional supplement or taking FA only, suggesting that women need to consider their own Vit.E nutritional status to choose the type of nutritional supplements during periconceptional period, so as to avoid related health hazards.

Despite recent advances in diagnosis and therapeutic strategies, treatment of non-small-cell lung cancer (NSCLC) remains unsatisfactory in terms of prognosis. Andrographolide (AD), a principal active component of Andrographis paniculata (Burm.f.) Nees, exerts anti-cancer therapeutic properties. AD has been used for centuries in China for clinical treatment of viral infections. However, the pharmacological biology of AD in NSCLC remains unknown. In this study, AD regulated autophagy and PD-L1 expression in NSCLC. Molecular dynamics simulations indicated that AD bound directly to signal transducer and activator of transcription-3 (STAT3) with high affinity. Proteomics analysis indicated that AD reduced the expression of tumour PD-L1 in NSCLC by suppressing JAK2/STAT3 signalling. AD modulated the P62-dependent selective autophagic degradation of PD-L1 by inhibiting STAT3 phosphorylation. In vivo study revealed that AD suppressed tumour growth in H1975 xenograft mice and Lewis lung carcinoma cell models, and better efficacy was obtained at higher concentrations. AD prolonged the survival time of the mice and enhanced the treatment efficacy of anti-PD-1 mAb immunotherapy by stimulating CD8 + T cell infiltration and function. This work elucidated the specific mechanism by which AD inhibited NSCLC. Treatment with the combination of AD and anti-PD-1 mAb immunotherapy could be a potential strategy for patients with NSCLC., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

De-etiolation is indispensable for seedling survival and development. However, how sugars regulate de-etiolation and how sugars induce ethylene (ET) for seedlings to grow out of soil remain elusive. Here, we reveal how a sucrose (Suc) feedback loop promotes de-etiolation by inducing ET biosynthesis. Under darkness, Suc in germinating seeds preferentially induces 1-amino-cyclopropane-1-carboxylate synthase (ACS7; encoding a key ET biosynthesis enzyme) and associated ET biosynthesis, thereby activating ET core component ETHYLENE-INSENSITIVE3 (EIN3). Activated EIN3 directly inhibits the function of Suc transporter 2 (SUC2; a major Suc transporter) to block Suc export from cotyledons and thereby elevate Suc accumulation of cotyledons to induce ET. Under light, ET-activated EIN3 directly inhibits the function of phytochrome A (phyA; a de-etiolation inhibitor) to promote de-etiolation. We therefore propose that under darkness, the Suc feedback loop (Suc-ACS7-EIN3-|SUC2-Suc) promotes Suc accumulation in cotyledons to guarantee ET biosynthesis, facilitate de-etiolation, and enable seedlings to grow out of soil., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Lung cancer has become the principal cause of cancer-related deaths. Emodin is a Chinese herb-derived compound extracted from the roots of Rheum officinale that exhibits numerous pharmacological characteristics. Secretory phospholipase A2-IIa (sPLA2-IIa) is overexpressed in cancers and plays an important role in cancer development., Purpose: This study aims to investigate the anti-tumor mechanism of emodin in non-small-cell lung cancer (NSCLC)., Methods: MTT assay was applied to detect the sensitivity of emodin to NSCLC cell line. Flow cytometry was used to examine the effect of emodin on cell cycle distribution and evaluate ROS level and apoptosis. Western blot analysis was utilised to examine the expression levels of sPLA2-IIa, PKM2, and AMPK and its downstream pathways induced by emodin. Enzyme inhibition assay was applied to investigate the inhibitory effect of emodin on sPLA2-IIa. The anticancer effect of emodin was also detected using an in vivo model., Results: Emodin significantly inhibited NSCLC proliferation in vivo and in vitro and was relatively less cytotoxic to normal lung cell lines. Most importantly, emodin inhibited the proliferation of KRAS mutant cell lines by decreasing the expression of sPLA2-IIa and NF-κB pathways. Emodin also inhibited mTOR and AKT and activated the AMPK pathway. Furthermore, emodin induced apoptosis, increased the reactive oxygen species (ROS) level, and arrested the cell cycle., Conclusion: Emodin exhibited a novel anti-tumor mechanism of inhibiting the proliferation of KRAS mutant cell lines by decreasing the expression levels of sPLA2-IIa and NF-κB pathways. Hence, emodin can potentially serve as a therapeutic target in NSCLC., (Copyright © 2021. Published by Elsevier GmbH.)

Periodontitis is a chronic inflammatory disease induced by Porphyromonas gingivalis (P. gingivalis) and other pathogens. P. gingivalis release various virulence factors including lipopolysaccharide (LPS). However, whether P. gingivalis-LPS inducing pyroptosis in human gingival fibroblasts (HGFs) remains unknown. In present study, P. gingivalis-LPS decreased the membrane integrity of HGFs, and pyroptosis-associated cytokines were upregulated at the mRNA level. In addition, pyroptosis proteins were highly expressed in gingival tissues of periodontitis. P. gingivalis-LPS induced gingivitis in the rat model, and the expression level of pyroptosis-associated proteins increased. Together, P. gingivalis-LPS can activate the pyroptosis reaction, which may be a pro-pyroptosis status in a relative low concentration.

Background: Cervical cancer continues to be one of the leading causes of cancer deaths among females in low and middle-income countries. In this study, we aimed to assess the independent prognostic value of clinical and potential prognostic factors in progression-free survival (PFS) in cervical cancer., Methods: We conducted a retrospective study on 92 cervical cancer patients treated from 2017 to 2019 at the Zhuhai Hospital of Traditional Chinese and Western Medicine. Tumor characteristics, treatment options, progression-free survival and follow-up information were collected. Kaplan-Meier method was used to assess the PFS., Results: Results showed that the number of retrieved lymph nodes had a statistically significant effect on PFS of cervical cancer patients (P = 0.002). Kaplan-Meier survival curve analysis showed that cervical cancer patients with initial symptoms age 25-39 had worse survival prognoses (P = 0.020). And the using of uterine manipulator in laparoscopic treatment showed a better prognosis (P < 0.001). A novel discovery of our study was to verify the prognostic values of retrieved lymph nodes count combining with FIGO staging system, which had never been investigated in cervical cancer before. According to the Kaplan-Meier survival curve analysis and receiver operating characteristic (ROC) curve analysis, significant improvements were found after the combination of retrieved lymph nodes count and FIGO stage in predicting PFS for cervical cancer patients (P < 0.001, AUC = 0.826, 95% CI: 0.689-0.962)., Conclusion: Number of retrieved lymph nodes, initial symptoms age, uterine manipulator, and retrieved lymph nodes count combining with FIGO staging system could be potential prognostic factors for cervical cancer patients.

Early diagnosis has been proved to improve survival rate of lung cancer patients. The availability of blood-based screening could increase early lung cancer patient uptake. Our present study attempted to discover Chinese patients' plasma metabolites as diagnostic biomarkers for lung cancer. In this work, we use a pioneering interdisciplinary mechanism, which is firstly applied to lung cancer, to detect early lung cancer diagnostic biomarkers by combining metabolomics and machine learning methods. We collected total 110 lung cancer patients and 43 healthy individuals in our study. Levels of 61 plasma metabolites were from targeted metabolomic study using LC-MS/MS. A specific combination of six metabolic biomarkers note-worthily enabling the discrimination between stage I lung cancer patients and healthy individuals (AUC = 0.989, Sensitivity = 98.1%, Specificity = 100.0%). And the top 5 relative importance metabolic biomarkers developed by FCBF algorithm also could be potential screening biomarkers for early detection of lung cancer. Naïve Bayes is recommended as an exploitable tool for early lung tumor prediction. This research will provide strong support for the feasibility of blood-based screening, and bring a more accurate, quick and integrated application tool for early lung cancer diagnostic. The proposed interdisciplinary method could be adapted to other cancer beyond lung cancer., 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 © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To find out the status of folic acid supplementation among women, to evaluate the prevention effects on neural tube defects (NTDs), and to explore the factors impact on folic acid supplementation compliance., Methods: Based on the routine data of 92 121 women in prenatal health care and birth defect surveillance system in Tongzhou District of Beijing from 2013 to 2018, we described the prevalence of periconceptional folic acid supplementation, pre-pregnancy folic acid supplementation and regularly folic acid supplementation (compliance supplementation). Trend χ 2 tests were used to evaluate the change of folic acid supplementation prevalence. The prevalence difference among the women with folic acid supplementation and without supplementation were tested with Fisher's exact test. Factors asso-ciated with folic acid supplementation compliance rate were analyzed with univariate and multivariate Logistic regression model., Results: The prevalence of periconceptional folic acid supplementation during the six years was 90.08% and it was increased from 2013 to 2018, but the rate of pre-pregnancy and regular supplementation was only 41.5% and declined from 2013 to 2018, especially 2013 to 2015. The prevalence of NTDs among the fetuses whose mothers took folic acid during periconceptional period was 5.5/10 000, while the prevalence for the fetuses whose mothers did not take folic acid was 19.7/10 000 ( P < 0.001), the rates ratio was 27.9% ( χ 2 =23.74, P < 0.001). The difference between the prevalence of NTDs among the fetuses whose mothers took folic acid only and multiple micronutrients was not statistically significant. After controlling the confounding factors, it was found that the compliant folic acid supplementation rates in women, whose household registrations were outside Beijing and whose education levels were junior high school or below, and who were younger than 25 years old, and who were multiparas and who were pre-pregnancy underweight or obese, were lower than those of the corresponding control groups ( P < 0.05)., Conclusion: The rate of folic acid supplementation among women in Tongzhou District of Beijing was relatively high, but their compliance was poor. Women who did not take folic acid during periconception seriously affected the prevention effect of NTDs. We should focus on women who are younger than 25 years old, lower educated, pre-pregnancy underweight or obese, multiparas and nonlocal household registers, in order to improve the periconceptional folic acid supplementation compliance and improve the effects of NTDs prevention.

Objective: To investigate the incidence of hypertension disorders complicating pregnancy (HDCP) and vitamin E (VE) nutritional status among pregnant women in Beijing, and to determine the relationship between serum VE concentration in the first trimester of pregnancy and the risk of developing HDCP., Methods: A retrospective cohort study was performed including 22 283 cases of pregnant women who underwent singleton deliveries in Tongzhou Maternal & Child Health Hospital of Beijing from January 2016 through December 2018 and received tests of serum VE concentrations in the first trimester of pregnancy. Nonconditional Logistic regression model was used to analyze the association between serum VE concentration levels and the risk of developing HDCP., Results: The total incidence of HDCP was 5.4%, with the incidence of gestational hypertension around 2.1% and the incidence of preeclampsia-eclampsia around 3.3%. The median concentration of serum VE in early pregnancy was 10.1 (8.8-11.6) mg/L, and 99.7% of the participants had normal serum VE concentrations. The incidence of gestational hypertension and that of preeclampsia-eclampsia had been annually increasing in three years; a linear-by-linear association had also been observed between the serum VE concentrations and the years of delivery. According to the results of the univariable and the multivariable Logistic regression analyses, higher risks of developing HDCP had been observed among women with higher serum VE concentrations. Compared to those with serum VE concentrations in interquartile range ( P 25 - P 75 ) of all the participants, the women whose serum VE concentrations above P 75 were at higher risks to be attacked by HDCP ( OR = 1.34, P < 0.001), gestational hypertension ( OR = 1.39, P = 0.002), or preeclampsia-eclampsia ( OR = 1.34, P = 0.001), as suggested by the results of the multivariable Logistic regression model analyses. In addition, the women with serum VE concentrations of 11.2 mg/L or above had a significantly higher risk of developing HDCP than those whose serum VE concentrations of P 40 - P 60 of all the participants, and this risk grew higher as serum VE concentrations in the first trimester of pregnancy increased., Conclusion: Women in Beijing are at good nutritional status. From January 2016 to December 2018, the incidence of HDCP increased with serum VE concentration level, and serum VE concentration of 11.2 mg/L is an indicator of an increased risk of developing HDCP, suggesting that pregnant women should take nutritional supplements containing VE carefully.

Porphyromonas gingivalis (P. gingivalis) is one of the major pathogenic bacteria of periodontitis or peri-implantitis. P. gingivalis tends to attach to the implant's neck with the formation of biofilm, leading to peri-implantitis. d-arginine has been shown to have a potential antimicrobial role. In this study, P. gingivalis was cultured in Brain Heart Infusion broth together with d-arginine. After 3 days (inhibition) or 6 days (dissociation), these were characterized using crystal violet (CV) staining for the biofilm, extracellular polysaccharide (EPS) production from the biofilm, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay for biofilm activation. Furthermore, the P. gingivalis biofilm was observed by scanning electron microscopy (SEM). d-arginine effectively reduced biomass accumulation and promoted dissociation at concentrations of ≥50 mM and 100 mM, respectively. Through CV staining, d-arginine concentrations of EPS production from the biofilm for inhibition and dissociation effects was ≥50 mM and 100 mM, respectively. In addition, d-arginine affected biofilm activation for the corresponding concentrations: ≥60 mM for inhibition and ≥90 mM for dispersal. Under SEM observation, d-arginine changed the P. gingivalis biofilm structure in relatively high concentrations for inhibition or dissociation, respectively. The authors concluded that d-arginine could inhibit the formation of P. gingivalis biofilm and promote the dissociation of P. gingivalis biofilm.

Although electroacupuncture (EA) has become a worldwide practice, little is understood about its precise target in the central nervous system (CNS) and the cell type-specific analgesia mechanism. In the present study, we found that EA has significant antinociceptive effects both in inflammatory and neuropathic pain models. Chemogenetic inhibition of GABAergic neurons in the ventrolateral periaqueductal gray (vlPAG) replicated the effects of EA, whereas the combination of chemogenetic activation of GABAergic neurons and chemogenetic inhibition of glutamatergic neurons in the vlPAG was needed to reverse the effects of EA. Specifically knocking out CB1 receptors on GABAergic neurons in the vlPAG abolished the EA effect on pain hypersensitivity, while specifically knocking out CB1 receptors on glutamatergic neurons attenuated only a small portion of the EA effect. EA synchronously inhibits GABAergic neurons and activates glutamatergic neurons in the vlPAG through CB1 receptors to produce EA-induced analgesia. The CB1 receptors on GABAergic neurons localized in the vlPAG was the basis of the EA effect on pain hypersensitivity. This study provides new experimental evidence that EA can bidirectionally regulate GABAergic neurons and glutamatergic neurons via the CB1 receptors of the vlPAG to produce analgesia effects.

Background: Gestational diabetes mellitus (GDM) is usually diagnosed between 24th and 28th gestational week using the 75-g oral glucose tolerance test (OGTT). It is difficult to predict GDM before 24th gestational week because fast plasma glucose (FPG) decreases as the gestational age increases. It is controversial that if FPG ≥5.1 mmol/L before 24th gestational week should be intervened or not. The aim of this study was to evaluate the value of FPG to screen GDM before 24th gestational week in women with different pre-pregnancy body mass index (BMI)., Methods: This was a multi-region retrospective cohort study in China. Women who had a singleton live birth between June 20, 2013 and November 30, 2014, resided in Beijing, Guangzhou and Chengdu, and received prenatal care in 21 selected hospitals, were included in this study. Pre-pregnancy BMI, FPG before the 24th gestational week, and one-step GDM screening with 75 g-OGTT at the 24th to 28th gestational weeks were extracted from medical charts and analyzed. The pregnant women were classified into four groups based on pre-pregnancy BMI: Group A (underweight, BMI < 18.5 kg/m), Group B (normal, BMI 18.5-23.9 kg/m), Group C (overweight, BMI 24.0-27.9 kg/m) and Group D (obesity, BMI ≥28.0 kg/m). The trend of FPG before 24th week of gestation was described, and the sensitivity and specificity of using FPG before the 24th gestational week to diagnose GDM among different pre-pregnancy BMI groups were reported. Differences in the means between groups were evaluated using independent sample t-test and analysis of variance. Pearson Chi-square test was used for categorical variables., Results: The prevalence of GDM was 20.0% (6806/34,087) in the study population. FPG decreased gradually as the gestational age increased in all pre-pregnancy BMI groups until the 19th gestational week. FPG was higher in women with higher pre-pregnancy BMI. FPG before the 24th gestational week and pre-pregnancy BMI could be used to predict GDM. The incidence of GDM in women with FPG ≥5.10 mmol/L in the 19th to 24th gestational weeks and pre-pregnancy overweight or obesity was significantly higher than that in women with FPG ≥5.10 mmol/L and pre-pregnancy BMI <24.0 kg/m (78.5% [62/79] vs. 52.9% [64/121], χ = 13.425, P < 0.001)., Conclusions: FPG decreased gradually as the gestational age increased in all pre-pregnancy BMI groups until the 19th gestational week. Pre-pregnancy overweight or obesity was associated with an increased FPG value before the 24th gestational week. FPG ≥5.10 mmol/L between 19 and 24 gestational weeks should be treated as GDM in women with pre-pregnancy overweight and obesity.

Recent studies have exhibited significant roles of lncRNAs in various tumors' development, including colon cancer. Our study focused on the biological roles of lncRNA MALAT1 in colon cancer. In our study, it was demonstrated that MALAT1 was upregulated in human colon cancer cell lines including Lovo, HCT116, SW480, and HT29 cells compared to the normal human intestinal epithelial HIEC cells. Moreover, we observed that miR-129-5p was downregulated in colon cancer cells with a significant increase of HMGB1 expression. Inhibition of MALAT1 can inhibit the proliferation of colon cancer SW480 and HCT116 cells and next, bioinformatics analysis was used to predict the target microRNA of MALAT1. miR-129-5p was identified and confirmed as a direct regulator of MALAT1 and it was shown that miR-129-5p mimics were able to restrain the progression of colon cancer cells. In addition, high motility group box protein 1 (HMGB1), was predicted as a mRNA target of miR-129-5p. Furthermore, we found that MALAT1 exerted its biological functions through regulating HMGB1 by sponging miR-129-5p in vitro. Silencing MALAT1 greatly inhibited HMGB1 expression which can be reversed by miR-129-5p inhibitors. It was indicated in our investigation that MALAT1 may serve as a competing endogenous lncRNA (ceRNA) to mediate HMGB1 by sponging miR-129-5p in colon cancer. Taken together, our results indicated that MALAT1/miR-129-5p/HMGB1 axis could be provided as an important prognostic biomarker in colon cancer development., (© 2017 Wiley Periodicals, Inc.)

Rats of OXYS strain are characterized by genetically defined accelerated senescence. Ceftriaxone (CEF) exerts neuroprotective effects by decreasing the excitotoxicity and activation of antioxidant system. Here, we studied the effects of CEF (50 or 100mg/kg/day, i.p., 36 days) on cognitive and neuronal deficits in 5-month-old OXYS rats. Chronic CEF administration in a dose of 100mg/kg partially inhibited impairments of movement and restored the deficit in the novel object recognition in OXYS rats. Neuromorphologically, control OXYS rats exhibited a lowered neuronal density in the hippocampal CA1 area and there was a tendency to decrease in the substantia nigra pars compacta compared to Wistar controls. Both doses of CEF increased the density of pyramidal neurons in the CA1 area in OXYS rats. Control OXYS rats demonstrated a tendency to lower tyrosine hydroxylase (TH) immunoreactivity in the striatum compared with Wistar rats, while CEF treatment at a dose of 50mg/kg significantly augmented this parameter. In control OXYS rats, the levels of neurogenesis in the subgranular zone of the dentate gyrus of the hippocampus were significantly higher than in Wistar rats indicating compensatory processes that probably prevented the further induction of neurogenesis by CEF. Restoration of the recognition function and neuronal density in the CA1 area in OXYS rats after CEF treatment might be related to activation of the mechanisms that provide survival of newborn and mature neurons. The data suggested CEF as a promising pharmacological tool for the prevention of cognitive decline at accelerated aging., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Hyperactivity of the glutamatergic system is involved in excitotoxicity and neurodegeneration in Parkinson's disease (PD) so that glutamatergic modulation maybe a potential therapeutic target for PD. Ceftriaxone (CEF) has been reported to increase glutamate uptake by increasing glutamate transporter expression and has been demonstrated neuroprotective effects in animal study. The aim of this study was to determine the effects of CEF on behavior and neurogenesis in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model. MPTP was stereotaxically injected into the substantia nigra pars compacta (SNc) of male Wistar rats. Starting on the same day after MPTP lesioning (day 0), the rats were injected daily with either CEF or saline for 14days and underwent a T-maze test on days 8-10 and an object recognition test on days 12-14, then the brain was taken for histological evaluation on day 15. The results showed that MPTP lesioning resulted in decreased motor function, working memory, and object recognition and reduced neurogenesis in the substantial nigra and dentate gyrus of the hippocampus. These behavioral and neuronal changes were prevented by CEF treatment. To our knowledge, this is the first study showing that CEF prevents loss of neurogenesis in the brain of PD rats. CEF may therefore have clinical potential in the treatment of PD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: We aimed to assess the prevalence and risk factors for hypertensive disorders and to study the main pregnancy outcomes in the Beijing area of China., Study Design: This study randomly sampled 15 hospitals in Beijing from Jun 2013 to Nov 2013 and evaluated 15 194 deliveries. Logistic regression analysis was used to study the association between risk factors and hypertensive disorders. Pregnancy outcomes included preterm birth, cesarean delivery and small for gestational age (SGA)., Results: The prevalence of hypertensive disorders, preeclampsia (PE) and severe PE was 4.4, 2.7 and 1.8%, respectively. The risk factors for hypertensive disorders and severe PE were maternal body mass index before pregnancy, gestational weight gain (GWG), gestational diabetes and pre-gestational diabetes, and third trimester cholesterol (CHOL) levels. First trimester high-density lipoprotein was a protective factor for severe PE. The incidence of hypertensive disorders increased with maternal age. Preterm delivery, cesarean delivery and small infant size for gestational age were more prevalent in the severe PE group compared with the non-hypertensive group., Conclusions: In the Beijing area of China, maternal body mass index before pregnancy, GWG, maternal complications of gestational diabetes and pre-gestational diabetes, and third trimester CHOL levels are risk factors for both hypertensive disorders of pregnancy and severe PE. First trimester high-density lipoprotein is a protective factor for severe PE. Severe preeclampsia leads to a higher incidence of preterm delivery, cesarean delivery and SGA infants.

Objective: To evaluate the effect of platelet-rich fibrin extract (PRFe) on the adhesion, proliferation and differentiation of MC3T3-E1 cells cultured on the titanium discs. Methods: Samples were divided into experimental group (P) and control group (D). Group P used the α-minimal essential medium (α-MEM) containing PRFe (0.5%), while group D used only the α-MEM. Cell adhesion and cytoskeleton were observed using scanning electron microscopy (SEM) and laser scanning confocal microscopy (LSCM). Methyl thiazolyl tetrazolium (MTT) assay to detect the number of the osteoblasts at 1, 3, 5, 7 d; the activity of alkaline phosphatase (ALP) to detect the differentiation of osteoblast at 1, 3, 5, 7 d; the level of osteogenetic biomarkers core-binding factorα1 (cbfα1) and osteocalcin (OCN) were quantified by quantitative real-time PCR (qRT-PCR) at 3 and 7 d. Results: SEM and LSCM showed that the adhesion and filaments of group P were higher than those of group D at each time point. MTT assay showed that the absorbance were significantly increased in group P (1 d: 0.299±0.002, 3 d: 0.517±0.004, 5 d: 0.810±0.002, 7 d: 1.203±0.011) compared with group D (1 d: 0.198±0.003, 3 d: 0.399±0.002, 5 d: 0.588±0.002, 7 d: 0.897±0.005) at each time points ( P< 0.05). Furthermore, the ALP activity of group P (1 d: 0.162±0.004, 3 d: 0.289±0.001, 5 d: 0.491±0.006, 7 d: 0.647±0.005) was significantly higher than that of group D (1 d: 0.121±0.003, 3 d: 0.191± 0.006, 5 d: 0.252±0.004, 7 d: 0.365±0.012), ( P< 0.05). Moreover, the qRT-PCR showed that the Cbfα1 and OCN gene expression in group P (Cfbα1, 3 d: 1.50±0.04, 7 d: 1.94±0.06; OCN, 3 d: 3.37±0.17, 7 d: 3.92± 0.04) were significantly higher than that in group D(Cfbα1, 3 d: 1, 7 d: 1.18±0.13; OCN, 3 d: 1, 7 d: 2.34± 0.09) ( P< 0.05). Conclusions: PRFe promoted the adhension, proliferation and differentiation of MC3T3-E1 cells on the titanium discs.

The current study investigated the effects of phased joint intervention on clinical efficacy and Rho/Rho-associated coil protein kinase (ROCK) expression in patients with portal hypertension complicated by esophageal variceal bleeding (EVB) and hypersplenism. Patients with portal hypertension (n=53) caused by liver cirrhosis complicated by EVB and hypersplenism treated with phased joint intervention were assessed, and portal hemodynamics, blood, liver function, complications, and rebleeding incidence were analyzed. Reverse transcription-quantitative polymerase chain reaction was used to measure Rho, ROCK1 and ROCK2 mRNA expression levels in peripheral blood mononuclear cells prior to and following phased joint intervention, and western blotting was employed to determine the protein expression levels of Rho, ROCK1, ROCK2, phosphorylated (p) myosin phosphatase target subunit 1 (MYPT1) and total-MYPT1. All patients underwent an emergency assessment of hemostasis with a 100% success rate. Varicose veins were alleviated, and portal hemodynamics and liver function improved following intervention. Furthermore, preoperative and postoperative expression levels of Rho, ROCK1 and ROCK2 mRNA were higher compared with the control group. Notably, the mRNA expression levels of Rho, ROCK1 and ROCK2 in the postoperative group were significantly lower when compared with the preoperative group. Protein expression levels of Rho, ROCK1, ROCK2 and pMYPT1 in the postoperative group were lower, as compared with the preoperative group. Concentration levels of transforming growth factor-β1, connective tissue growth factor and platelet-derived growth factor in peripheral blood were significantly reduced following phased joint intervention. Therefore, the present findings demonstrated that phased joint intervention is able to effectively treat EVB and hypersplenism, and improve liver function. The efficacy of phased joint intervention may be associated with its role in the regulation of the Rho-ROCK signaling pathway.

Background: Impact of atrial fibrillation on clinical outcomes is well recognized, and application of renin-angiotensin-aldosterone system (RAAS) blockers for the prevention of atrial fibrillation (AF) is a theoretically appealing concept. However, clinical trials have yielded inconsistent results., Methods: A pooled study of 26 randomized controlled trials (RCTs) assessing the efficacy of RAAS blockers on AF prophylaxis was performed., Results: A total of 28 reports from 26 randomized controlled trials enrolled 165 387 patients, with an overall 24% reduction in the incidence of AF (odds ratio [OR]: 0.76, 95% confidence interval [CI]: 0.68-0.85], P = .000). Forty-nine percent reduction in the incidence of AF (OR: 0.51, 95% CI: 0.30-0.85, P = .010) in systolic heart failure was observed, whereas no significant effect was observed in patients with diastolic heart failure, postmyocardial infarction, and high cardiovascular disease risk. There was a 19% (OR: 0.81, 95% CI: 0.67-1.00, P = .037) reduction in new-onset and 54% (OR: 0.46, 95% CI: 0.33-0.62, P = .000) reduction in recurrent AF in hypertensive patients with 39% (OR: 0.61, 95% CI: 0.44-0.84, P = .003) risk reduction against calcium blockers and 41% (OR: 0.59, 95% CI: 0.44-0.80, P = .001) risk reduction against β blockers. Angiotensin-receptor blocker appeared marginally superior to angiotensin-converting enzyme inhibitor in primary and secondary prevention., Conclusion: This study suggests that RAAS blockade effectively suppresses AF in systolic heart failure, and hypertensives derive greater benefit against new-onset and recurrent AF compared to β blockers, calcium channel blockers, and diuretics., (© The Author(s) 2016.)

Manganese-enhanced magnetic resonance imaging (MEMRI) is a widely used technique for detecting neuronal activity in the brain of a living animal. Ceftriaxone (CEF) has been shown to have neuroprotective effects in neurodegenerative diseases. The present study was aimed at clarifying whether, in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) rat model, the known CEF-induced neuronal protection was accompanied by neurogenesis and decreased loss of neuronal activity. After MPTP lesioning (day 0), the rats were treated with CEF (100mg/kg/day, i.p.) or saline for 15 days. They were then injected with MnCl2 (40mg/kg, i.p.) on day 13 and underwent a brain MRI scan on day 14, then the brain was taken for histological evaluation on day 15. The results showed that MPTP lesioning resulted in decreased neuronal activity and density in the nigrostriatal dopaminergic (DAergic) system and the hippocampal CA1, CA3, and dentate gyrus (DG) areas and reduced neurogenesis in the DG, but in hyperactivity in the subthalamic nucleus (STN). These neuronal changes were prevented by CEF treatment. Positive correlations between MEMRI R1 values and neuronal density in the hippocampus were evidenced. Neuronal densities in the hippocampus and SNc were positively correlated. In addition, the R1 value of the STN showed a positive correlation with its neuronal activity but showed a negative correlation with the density of DAergic neurons in the SNc. Therefore, MEMRI R1 value may serve as a good indicator for PD severity and the effect of treatment. To our knowledge, this is the first study showing that CEF prevents loss of neuronal activity and neurogenesis in the brain of PD rats. CEF may therefore have clinical potential in the treatment of PD., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Road traffic accidents are the leading health threat to children and cause significant long-term mental health problems. This study aimed to characterize posttraumatic stress disorder (PTSD) in children suffering from road traffic injuries (RTIs) in Wenzhou, China., Methods: We conducted a retrospective study of 537 children (aged 1 to 13 years old) with RTIs. The epidemiological features, PTSD incidence, clinical manifestation, and risk factors were analyzed based on a customized PTSD risk factor questionnaire. The outcome factors were also evaluated by means of the logistic regression method., Results: The PTSD incidence was 24.77% in children with RTIs. The incidence of PTSD was related to the personality, family environment, and family care of the children. It was found that early psychological intervention and reasonable family care from the family might promote physical and mental welfare as well as contribute to the development of more effective treatments to prevent PTSD., Conclusion: For susceptible children, in addition to dealing with the somatic injury, psychological intervention and family care should be carried out as early as possible.

Objective: To estimate the risk of adverse maternal and perinatal outcomes in women with different pre-pregnancy body mass index (BMI)., Methods: We conducted a cohort study with 14 451 singleton pregnancies in 15 medical centers in Beijing between 20 June 2013 and 30 November 2013 using cluster random sampling. We divided participants into four groups based on pre-pregnancy BMI: Group A (underweight): BMI < 18.5 kg/m(2), Group B (normal): 18.5-23.9 kg/m(2), Group C (overweight): 24-27.9 kg/m(2), Group D (obesity): ≥28 kg/m(2). We used multivariate analysis to evaluate the association of the risk of adverse pregnancy outcomes and pre-pregnancy BMI., Results: The prevalence of maternal overweight and obesity was 14.82% (2142/14 451) and 4.71% (680/14 451) in the study population, respectively. Higher pre-pregnancy BMI is associated with higher prevalence of gestational diabetes (GDM), macrosomia, Cesarean section (C-section), preeclampsia and postpartum hemorrhage. Pre-pregnancy overweight or obesity increases the risk of adverse pregnancy outcomes, regardless of GDM status., Conclusions: Pre-pregnancy overweight or obesity is associated with increased risk of adverse pregnancy outcomes. Nutrition counseling is recommended before pregnancy in women who have overweight or obesity.

Aim: To explore the effect of the histone deacetylase inhibitor givinostat on proteins related to regulation of hepatic stellate cell proliferation., Methods: The cell counting kit-8 assay and flow cytometry were used to observe changes in proliferation, apoptosis, and cell cycle in hepatic stellate cells treated with givinostat. Western blot was used to observe expression changes in p21, p57, CDK4, CDK6, cyclinD1, caspase-3, and caspase-9 in hepatic stellate cells exposed to givinostat. The scratch assay was used to analyze the effect of givinostat on cell migration. Effects of givinostat on the reactive oxygen species profile, mitochondrial membrane potential, and mitochondrial permeability transition pore opening in JS-1 cells were observed by laser confocal microscopy., Results: Givinostat significantly inhibited JS-1 cell proliferation and promoted cell apoptosis, leading to cell cycle arrest in G0/G1 phases. Treatment with givinostat downregulated protein expression of CDK4, CDK6, and cyclin D1, whereas expression of p21 and p57 was significantly increased. The givinostat-induced apoptosis of hepatic stellate cells was mainly mediated through p38 and extracellular signal-regulated kinase 1/2. Givinostat treatment increased intracellular reactive oxygen species production, decreased mitochondrial membrane potential, and promoted mitochondrial permeability transition pore opening. Acetylation of superoxide dismutase (acetyl K68) and nuclear factor-κB p65 (acetyl K310) was upregulated, while there was no change in protein expression. Moreover, the notable beneficial effect of givinostat on liver fibrosis was also confirmed in the mouse models., Conclusion: Givinostat has antifibrotic activities via regulating the acetylation of nuclear factor-κB and superoxide dismutase 2, thus inhibiting hepatic stellate cell proliferation and inducing apoptosis.

The antibiotic salinomycin (Salin) was recently identified as an antitumor drug for the treatment of several types of solid tumors. However, the effects of Salin on the migratory and invasive properties of hepatocellular carcinoma (HCC) cells are unclear. The present study aimed to determine the antitumor efficacy and mechanism of Salin in HCC cells. Human HCC cells (HCCLM3) treated with Salin showed a concentration-dependent reduction in cell migration and invasion, and this was associated with reduced MMP9 expression. The MMP9 promoter and enhancer in a luciferase reporter assay revealed that Salin can regulate MMP9 expression through an activator protein (AP-1) site within the MMP9 enhancer. JunD, one of the AP-1 components, was significantly decreased by Salin in a concentration- and time-dependent manner. Salin was able to induce c-Jun NH2-kinase (JNK) phosphorylation and to block both JunD and MMP9 expression. Our results showed that JNK phosphorylation and JunD may be involved in the Salin-regulated MMP9 signaling pathway in HCCLM3 cells and may mediate HCC cell biological characteristics. Our studies provide new insight into the antitumor effects of Salin.

Objective: To explore the clinical characteristics of pregnant uterine rupture, enhance its early diagnosis rate and improve its prognosis., Methods: For this retrospective study, a total of 55 143 delivery cases at Tongzhou District Maternal & Child Health Hospital from January 1, 2003 to May 31, 2012 was analyzed. There were 2490 cases of scarred uterus and 68 cases had uterine rupture. And 62 of them belonged to scarred uterus rupture. And there were 52 653 cases of non-scarred uterus childbirth and 6 of them had rupture., Results: Significant differences existed in the rupture of scarred versus non-scarred uterus and maternal versus primipara women. Uterus rupture usually occurred at the incomplete rupture position of original surgical scar at 39 weeks or more. The scar thickness of lower uterine segment was ≤ 3 mm on ultrasound. Three cases with laparoscopic myoma removal within 1 year had complete rupture at 36-38 weeks. Postpartum hemorrhage incidence was 42.65%. There were two cases of hysterectomy and 11 cases of neonatal asphyxia., Conclusion: For second pregnancy of cesarean section, pregnancy should be terminated before 39 weeks if scar thickness of lower uterine segment is ≤ 3 mm. Late rupture is to be monitored closely for those with laparoscopic myoma removal within 1 year. Meanwhile, we should strengthen the management of migrant and unemployed women.

Objective: To investigate the treatment and prevention of infection after alveolar crest onlay bone graft., Methods: From January 2006 to May 2010, 11 infection cases after onlay graft on alveolar crest were reviewed to evaluate the infection time, clinical situation, treatment measure, and therapeutic effect., Results: The infection of all 11 cases occurred about 15 days after bone graft, which showed either soft tissue fistulae or bone graft exposure in the oral cavity. Three cases failed because of persistent infection. The infection of the other 8 cases was controlled after a series of comprehensive therapy, and most of the bone graft was reserved and implant restoration finally completed., Conclusions: After the effective and comprehensive therapy, infected bone graft can be reserved. But to ensure the survival rate of bone graft, the most important thing is to prevent infection in perioperative period.

Invasive Haemophilus influenzae type b (Hib) diseases are major causes of childhood morbidity and mortality. For the period from 1994 to 2003, we retrospectively identified 53 children with invasive Hib disease including 31 with meningitis, 14 with pneumonia, 2 with septic arthritis, 2 with epiglottitis, 1 with neutropenic sepsis, and 3 who were bacteraemic without a focus. Two children died and 22 had serious sequelae; significantly, survivors with sequelae had presented with meningitis (P-value<0.001) or sepsis (P-value=0.001). During the 11-year period, the annual incidence of invasive Hib disease was estimated to be 4.4/100,000 children <5 years old. With rising affluence, decreasing costs of vaccines, and increased costs in caring for survivors, universal infant immunization with Hib vaccine may need to be reconsidered in Singapore.

The basic phospholipase A(2) from the venom of Agkistrodon halys Pallas exhibits strong hemolytic activity. The enzyme has been crystallized by vapour diffusion techniques. Diffraction data of the crystal have been collected up to 2.5 Aring; resolution using the synchrotron radiation-imaging plate-Weissenberg camera system. The crystal parameters were calculated with an auto-indexing program. The crystal belongs to C2 space group with unit cell dimensions of alpha=100.38 Aring;, b=54.37 Aring;, c=117.38 Aring; and beta=120.71 deg;. Each asymmetric unit probably contains four or five molecules.