Core concomitant symptoms reported by the patients with breast cancer in postoperative endocrine treatment and the demand for acupuncture therapy： a network-based cross-sectional study. / ä¹³è ºç™Œæœ¯åŽå† åˆ†æ³Œæ²»ç–—æ‚£è€ æŠ¥å‘Šçš„æ ¸å¿ƒä¼´éšç—‡çŠ¶åŠå¯¹é’ˆç¸æ²»ç–—çš„éœ€æ±‚ï¼šä¸€é¡¹åŸºäºŽç½‘ç»œçš„æ¨ªæ–­é¢ç ”ç©¶.

OBJECTIVES: To investigate the most common concomitant symptoms and the urgent demand of solution in the breast cancer patients undergoing postoperative endocrine treatment, as well as the acceptance and expectation of acupuncture in the patients so as to provide the scientific data for promoting the application of acupuncture in the breast cancer patients. METHODS: Breast cancer patients treated in Tianjin Medical University Cancer Institute and Hospital from January 2022 to March 2023 were randomly selected as the subjects. Using "questionnaire star" website, the questionnaire was conducted to investigate the relevant concomitant symptoms of the patients in postoperative endocrine treatment and the questions related to acupuncture treatment. RESULTS: In this study, 229 questionnaires were distributed and 211 valid ones were collected, with the response rate of 92.1%. Among these patients, the first three common symptoms were sleep disorders (157 cases, 74.4%), hot flashes (138 cases, 65.4%) and joint / muscle pain (118 cases, 55.9%)；the top three symptoms to be solved the most urgently were sleep disorders (131 cases, 62.1%), joint / muscle pain (62 cases, 29.4%) and hot flashes (45 cases, 21.3%). 79.1% of the patients (167 cases) were willing to receive acupuncture treatment because of the high expectations on its potential effect (93%). 20.9% of them (44 cases) refused acupuncture because they were worried not to be treated by the experienced physicians of TCM (52%) or afraid of needling feelings (48%). The average expectation value of acupuncture treatment was 4.02 points (5 points for the total score) among patients willing to receive acupuncture treatment. The main purposes of receiring acupuncture for the patients undergoing endocrine treatment were to strengthen the immune function (92%), reduce the adverse reactions (83%), and improve the physical condition (75%), et al. CONCLUSIONS: Sleep disorder is one of the most concerned symptoms in endocrine treatment for the patients after breast cancer surgery. The patients highly expect for acupuncture treatment even though some patients dislike the needling sensation. How to provide the acceptable and high-quality acupuncture services for cancer patients will be one of the major directions of acupuncture research in the future.

[Coupling Mechanisms of Eco-environmental Quality and Human Activities in China and Their Influencing Factors].

In the context of sustainable development, it is important to thoroughly investigate the coupling mechanism between China's eco-environmental quality and human activities, as well as identify the influencing factors, in order to provide scientific references for achieving sustainable development goals in China. This study applied trend analysis, coupling coordination degree, LMDI, and optimal parameter geographic detector models to explore and evaluate the coupling mechanism between China's eco-environmental quality and human activities. The findings of the study were as follows:① During the research period, there was a growth trend in China's coupling coordination degree, human activities, and eco-environmental quality. Human activities and coupling coordination degree exhibited a spatial differentiation pattern with the Hu Line as the boundary, showing an "east high, west low" distribution. The eco-environmental quality demonstrated a "south high, north low" differentiation pattern. ② The overall trend of China's coupling coordination type transformation was shifting from lower-level to higher-level coordination types. ③ Based on the geographic detector and LMDI models, the dominant factors influencing the coupling coordination degree in most provinces east of the Hu Line were social and economic factors, as well as the comprehensive coordination index. In contrast, the dominant factors in most provinces west of the Hu Line were natural environmental factors and coupling degree. ④ The evaluation of the impact of changes in human activities on eco-environmental quality revealed that the regions east of the Hu Line were mainly characterized by favorable development and effective protection, whereas the regions west of the line were mainly characterized by destructive development and ineffective protection. It is suggested that the regions on both sides of the Hu Line should prioritize development based on local prerequisites influencing the coupling coordination degree and the relative relationship between human activities and eco-environmental quality. It is crucial to actively adjust development strategies and pursue a sustainable development path towards the high-level coordination between eco-environmental quality and human activities.

The Real Experience of Lay Responders Performing Cardiopulmonary Resuscitation: A Synthesis of Qualitative Evidence.

Objectives: To synthesize qualitative evidence on the experience of lay responders performing cardiopulmonary resuscitation (CPR). Methods: Qualitative evidence synthesis was performed using the Thomas and Harden method. The PubMed, Cochrane Library, Web of Science, OVID Medline, Embase, CINAHL, CNKI, and WanFang databases were systematically searched. The quality of the research was assessed by the Critical Assessment Skills Program Tool (CASP). Results: A total of 5,610 studies were identified, and 9 studies were included in the analysis. Four analytical themes were generated: emotional ambivalence before CPR, psychological tolerance during CPR, perceived experience after CPR, and enhancing psychological resilience. Conclusion: Lay responders face complicated psychological experience during CPR, which may be susceptible to psychological effects such as "loss aversion," "bystander effects" and "knowledge curse." In addition to the timely retraining of CPR, lay responders should be instructed to manage psychological distress and improve psychological resilience. More importantly, the psychological sequelae may be long-lasting, requiring ongoing psychological intervention and follow-up based on valuing transdisciplinarity across endeavours.

Mudanpioside C Discovered from Paeonia suffruticosa Andr. Acts as a Protein Disulfide Isomerase Inhibitor with Antithrombotic Activities.

Paeonia suffruticosa Andr. is a well-known landscape plant worldwide and also holds significant importance in China due to its medicinal and dietary properties. Previous studies have found that Cortex Moutan (CM), the dried root bark of P. suffruticosa, showed antiplatelet and cardioprotective effects, although the underlying mechanism and active compounds remain to be revealed. In this study, protein disulfide isomerase (PDI) inhibitors in CM were identified using a ligand-fishing method combined with the UHPLC-Q-TOF-MS assay. Further, their binding sites and inhibitory activities toward PDI were validated. The antiplatelet aggregation and antithrombotic activity were investigated. The results showed that two structurally similar compounds in CM were identified as the inhibitor for PDI with IC50 at 3.22 µM and 16.73 µM; among them Mudanpioside C (MC) is the most effective PDI inhibitor. Molecular docking, site-directed mutagenesis, and MST assay unequivocally demonstrated the specific binding of MC to the b'-x domain of PDI (Kd = 3.9 µM), acting as a potent PDI inhibitor by interacting with key amino acids K263, D292, and N298 within the b'-x domain. Meanwhile, MC could dose-dependently suppress collagen-induced platelet aggregation and interfere with platelet activation, adhesion, and spreading. Administration of MC can significantly inhibit thrombosis formation without disturbing hemostasis in mice. These findings present a promising perspective on the antithrombotic properties of CM and highlight the potential application of MC as lead compounds for targeting PDI in thrombosis therapy.

The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells.

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Alkali-Driven Photoinduced N-Dealkylation of Aryl Tertiary Amines and Amides.

By extending the photoinduced oxidative mechanism of aryl tertiary amines proposed earlier to an alkaline environment based on the prediction of quantum mechanics computations and the validation of meticulous experiments, we discovered a photoinduced oxidative N-dealkylation method for both aryl tertiary amines and amides. The dealkylation was achieved in an alkaline environment under mild conditions accompanied by excellent functional group tolerance.

Interferon-gamma and tumor necrosis factor-alpha synergistically enhance the immunosuppressive capacity of human umbilical-cord-derived mesenchymal stem cells by increasing PD-L1 expression.

BACKGROUND: The immunosuppressive capacity of mesenchymal stem cells (MSCs) is dependent on the "license" of several proinflammatory factors to express immunosuppressive factors such as programmed cell death 1 ligand 1 (PD-L1), which determines the clinical therapeutic efficacy of MSCs for inflammatory or immune diseases. In MSCs, interferon-gamma (IFN-γ) is a key inducer of PD-L1 expression, which is synergistically enhanced by tumor necrosis factor-alpha (TNF-α); however, the underlying mechanism is unclear. AIM: To reveal the mechanism of pretreated MSCs express high PD-L1 and explore the application of pretreated MSCs in ulcerative colitis. METHODS: We assessed PD-L1 expression in human umbilical-cord-derived MSCs (hUC-MSCs) induced by IFN-γ and TNF-α, alone or in combination. Additionally, we performed signal pathway inhibitor experiments as well as RNA interference experiments to elucidate the molecular mechanism by which IFN-γ alone or in combination with TNF-α induces PD-L1 expression. Moreover, we used luciferase reporter gene experiments to verify the binding sites of the transcription factors of each signal transduction pathway to the targeted gene promoters. Finally, we evaluated the immunosuppressive capacity of hUC-MSCs treated with IFN-γ and TNF-α in both an in vitro mixed lymphocyte culture assay, and in vivo in mice with dextran sulfate sodium-induced acute colitis. RESULTS: Our results suggest that IFN-γ induction alone upregulates PD-L1 expression in hUC-MSCs while TNF-α alone does not, and that the co-induction of IFN-γ and TNF-α promotes higher expression of PD-L1. IFN-γ induces hUC-MSCs to express PD-L1, in which IFN-γ activates the JAK/STAT1 signaling pathway, up-regulates the expression of the interferon regulatory factor 1 (IRF1) transcription factor, promotes the binding of IRF1 and the PD-L1 gene promoter, and finally promotes PD-L1 mRNA. Although TNF-α alone did not induce PD-L1 expression in hUC-MSCs, the addition of TNF-α significantly enhanced IFN-γ-induced JAK/STAT1/IRF1 activation. TNF-α up-regulated IFN-γ receptor expression through activation of the nuclear factor kappa-B signaling pathway, which significantly enhanced IFN-γ signaling. Finally, co-induced hUC-MSCs have a stronger inhibitory effect on lymphocyte proliferation, and significantly ameliorate weight loss, mucosal damage, inflammatory cell infiltration, and up-regulation of inflammatory factors in colitis mice. CONCLUSION: Overall, our results suggest that IFN-γ and TNF-α enhance both the immunosuppressive ability of hUC-MSCs and their efficacy in ulcerative colitis by synergistically inducing high expression of PD-L1.

Development of a circHIPK3-based ceRNA network and identification of mRNA signature in breast cancer patients harboring BRCA mutation.

Background: Exploring the regulatory network of competing endogenous RNAs (ceRNAs) as hallmarks for breast cancer development has great significance and could provide therapeutic targets. An mRNA signature predictive of prognosis and therapy response in BRCA carriers was developed according to circular RNA homeodomain-interacting protein kinase 3 (circHIPK3)-based ceRNA network. Method: We constructed a circHIPK3-based ceRNA network based on GSE173766 dataset and identified potential mRNAs that were associated with BRCA mutation patients within this ceRNA network. A total of 11 prognostic mRNAs and a risk model were identified and developed by univariate Cox regression analysis and the LASSO regression analysis as well as stepAIC method. Genomic landscape was treated by mutect2 and fisher. Immune characteristics was analyzed by ESTIMATE, MCP-counter. TIDE analysis was conducted to predict immunotherapy. The clinical treatment outcomes of BRCA mutation patients were assessed using a nomogram. The proliferation, migration and invasion in breast cancer cell lines were examined using CCK8 assay and transwell assay. Result: We found 241 mRNAs within the circHIPK3-based ceRNA network. An 11 mRNA-based signature was identified for prognostic model construction. High risk patients exhibited dismal prognosis, low response to immunotherapy, less immune cell infiltration and tumor mutation burden (TMB). High-risk patients were sensitive to six anti-tumor drugs, while low-risk patient were sensitive to 47 drugs. The risk score was the most effective on evaluating patients' survival. The robustness and good prediction performance were validated in The Cancer Genome Atlas (TCGA) dataset and immunotherapy datasets, respectively. In addition, circHIPK3 mRNA level was upregulated, and promoted cell viability, migration and invasion in breast cancer cell lines. Conclusion: The current study could improve the understanding of mRNAs in relation to BRCA mutation and pave the way to develop mRNA-based therapeutic targets for breast cancer patients with BRCA mutation.

Efficacy, Mechanism, and Structure-Activity Relationship of 6-Methoxy Benzofuran Derivatives as a Useful Tool for Senile Osteoporosis.

Most patients with senile osteoporosis (SOP) are severely deficient in bone mass, and treatments using bone resorption inhibitors, such as bisphosphonates, have shown limited efficacy. Small-molecule osteogenesis-promoting drugs are required to improve the treatment for this disease. Previously, we demonstrated that a compound with a benzofuran-like structure promoted bone formation by upregulating BMP-2, and it exhibited a therapeutic effect in SAMP-6 mice, glucocorticoid-induced osteoporosis rats, and ovariectomized rats. In this study, aged C57 and SAMP-6 mice models were used to investigate the therapeutic and preventive effects of compound 125 on SOP. scRNA-seq analysis showed that BMP-2 upregulation is the mechanism through which 125 accelerates bone turnover and increases the proportion of osteoblasts. We evaluated the structure-activity relationship of the candidate drugs and found that the derivative I-9 showed significantly higher efficacy than 125 and teriparatide in the zebrafish osteoporosis model. This study provides a foundation for the development of SOP drugs.

Noise Reduction Learning Based on XLNet-CRF for Biomedical Named Entity Recognition.

In recent years, Biomedical Named Entity Recognition (BioNER) systems have mainly been based on deep neural networks, which are used to extract information from the rapidly expanding biomedical literature. Long-distance context autoencoding language models based on transformers have recently been employed for BioNER with great success. However, noise interference exists in the process of pre-training and fine-tuning, and there is no effective decoder for label dependency. Current models have many aspects in need of improvement for better performance. We propose two kinds of noise reduction models, Shared Labels and Dynamic Splicing, based on XLNet encoding which is a permutation language pre-training model and decoding by Conditional Random Field (CRF). By testing 15 biomedical named entity recognition datasets, the two models improved the average F1-score by 1.504 and 1.48, respectively, and state-of-the-art performance was achieved on 7 of them. Further analysis proves the effectiveness of the two models and the improvement of the recognition effect of CRF, and suggests the applicable scope of the models according to different data characteristics.

Structure-based virtual screening identified novel FOXM1 inhibitors as the lead compounds for ovarian cancer.

Ovarian cancer (OC) is a gynecological tumor with possibly the worst prognosis, its 5-year survival rate being only 47.4%. The first line of therapy prescribed is chemotherapy consisting of platinum and paclitaxel. The primary reason for treatment failure is drug resistance. FOXM1 protein has been found to be closely associated with drug resistance, and inhibition of FOXM1 expression sensitizes cisplatin-resistant ovarian cancer cells. Combining existing first-line chemotherapy drugs with FOXM1 prolongs the overall survival of patients, therefore, FOXM1 is considered a potential therapeutic target in ovarian cancer. Previous research conducted by our team revealed a highly credible conformation of FOXM1 which enables binding by small molecules. Based on this conformation, the current study conducted virtual screening to determine a new structural skeleton for FOXM1 inhibitors which would enhance their medicinal properties. DZY-4 showed the highest affinity towards FOXM1, and its inhibitory effect on proliferation and migration of ovarian cancer at the cellular level was better than or equal to that of cisplatin, while its efficacy was equivalent to that of cisplatin in a nude mouse model. In this study, the anti-tumor effect of DZY-4 is reported for the first time. DZY-4 shows potential as a drug that can be used for ovarian cancer treatment, as well as a drug lead for future research.

Hepatic inhibitors expression profiling of venom-challenged Sinonatrix annularis and antidotal activities.

Snake venom is considered a "toxin arsenal", and it often induces a series of clinical and pathophysiological symptoms in snakebite victims. Interestingly, toxin inhibitors are commonly found in the serum of snakes and their predators. Sinonatrix annularis is a type of non-venomous snake that was reported to contain an "inhibitor cocktail", including phospholipase A2 inhibitors (PLIs), metalloproteinase inhibitors (SVMPIs), and small serum protein (SSP). However, the sequences and activities of these components remain obscure. In this study, we performed envenomation challenges on S. annularis using venoms from Deinagkistrodon acutus, Agkistrodon halys and Naja atra. In brief, the maximum injected amount of venom was 360 mg/kg for D. acutus, 72 mg/kg for A. halys, and 18 mg/kg for N. atra. The mRNA expression of the inhibitors PLIα, PLIß, PLIγ, SVMPI, serpin A1, and SSP showed a dose-dependent effect on envenomation. Liver homogenate from S. annularis (LH) was prepared and used to evaluate its inhibitory effect on snake venoms. As a result, LH showed significant neutralization of venom PLA2, mitigated hemorrhage, venom-induced muscle damage, and system toxicity. In the presence of LH, envenomated mice exhibited attenuated inflammation, apoptosis, oxidative damage, and mitigated changes in serum biochemical markers caused by venom. The study reveals the secret of "natural immunity" in snakes, namely, the "antivenom", which consists of an inhibitor proteome or cocktail.

[Effects of simulated precipitation changes on plant community characteristics of wetland in the Yellow River Delta, China]. / 模拟降雨量变化对黄河三角洲湿地植物群落特征的影响.

Under the changing climate scenario, changes in precipitation regimes are expected to alter soil water and salinity conditions, with consequences on the characteristics of plant community in estuarine wetland. Here, we used a six-year (2015-2020) precipitation manipulation experiment to examine how plant community characteristics responded to precipitation changes in the Yellow River Delta. The results showed that soil electrical conductivity significantly decreased, while soil moisture significantly increased with increasing precipitation. Precipitation changes altered plant community composition. Increased precipitation reduced the absolute dominance of Suaeda glauca and Suaeda salsa, but increased that of Triarrhena sacchariflora and Imperata cylindrica. Shannon index and Margalef richness index of plant community significantly increased with increasing precipitation. Compared with the control, both decreased and increased precipitation decreased the plant community abundance, frequency and coverage. The treatment of 60% increased precipitation significantly decreased plant community frequency by 54.9%, while the 60% decreased precipitation, 40% decreased precipitation, 40% increased precipitation and 60% increased precipitation treatment significantly decreased plant abundance by 38.9%, 33.8%, 35.8% and 45.7%, respectively. The aboveground biomass significantly increased with increasing precipitation, but aboveground plant biomass under 60% increased precipitation treatment being lower than that reducing under 40% increased precipitation treatment, probably due to the negative effects of flooding stress. In addition, Margalef richness index had a significantly positive relationship with aboveground biomass. Aboveground biomass, Shannon diversity index, Margalef richness index, and Simpson diversity index were negatively related to soil electrical conductivity, and aboveground plant biomass was positively related to soil moisture. Our results revealed that precipitation changes regulate growth characteristics, species composition, and diversity of plant community by altering soil water and salinity conditions in a coastal wetland.

Cornuside ameliorates cognitive impairments in scopolamine induced AD mice: Involvement of neurotransmitter and oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis Sieb. et Zucc., traditional Chinese medicine, has been widely used in the treatment of dementia. Cornel iridoid glycosides of Cornus officinalis is therapeutic to Alzheimer's disease (AD), while its pharmacodynamic material basis is not clear. Cornuside, an iridoid glycoside extracted from of Cornus officinalis Sieb. et Zucc, might be a potential anti-AD candidate. AIM OF THE STUDY: Cornuside was evaluated for its effect on scopolamine induced AD mice, and its action mechanisms were explored. MATERIALS AND METHODS: ICR mice were administered with 1 mg/kg scopolamine intraperitoneally to induce amnesia. The therapeutic effect of cornuside of cognitive function was evaluated via series of behavioral tests, including Morris water maze test, step-through test and step-down test. In addition, specific enzyme reaction tests were used to detect the content of acetylcholine (ACh) and malondialdehyde (MDA), as well as the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), choline acetyltransferase (ChAT), superoxide dismutase (SOD), catalase (CAT), monoamine oxidase (MAO) in the brain. The levels of monoamine neurotransmitters were detected by high performance liquid chromatography-electrochemical detection (HPLC-ECD). RESULTS: Cornuside ameliorated the spatial memory impairment in Morris water maze test and cognitive disruption in step-through and step-down test. Furthermore, cornuside improved the level of ACh by reducing the activities of AChE and BuChE, and increasing the activity of ChAT in hippocampus. Cornuside also increased the levels of monoamine neurotransmitters by inhibiting MAO activity in hippocampus and cortex. In addition, cornuside attenuated MDA by enhancing the activities of SOD and CAT in hippocampus and cortex. CONCLUSION: Cornuside improved cognitive dysfunction induced by scopolamine in behavioral tests. The mechanisms of cornuside were further investigated from the aspects of neurotransmitters and oxidative stress. Cornuside could inhibit oxidative stress and neurotransmitter hydrolases, increase ACh and monoamine neurotransmitters, which finally contributed to its therapeutic effect on scopolamine induced amnesia.

The molecular basis of venom resistance in the non-venomous snake Sinonatrix annularis.

Various snake species and snake predators have natural neutralization against snake toxins, which their antidotal abilities are commonly attributed to the intrinsic inhibitors produced by the liver, e.g., phospholipase A2 inhibitor (PLI) and metalloproteinase inhibitor (SVMPI). Sinonatrix annularis was found to possess broad-spectrum neutralization to different snake venoms in our lab. Although the anti-venom compound PLIγ has been previously characterized in our laboratory, the mechanism of resistance of S. annularis to snake venoms remains obscure. In this research, a venom affinity chromatography was constructed by immobilizing D. acutus venom to NHS-agarose beads and applied for antitoxins mining from S. annularis. The binding capacity of the venom column was validated using a self-prepared rabbit antivenom against D. acutus. Serum and liver homogenate of S. annularis were then applied to the column, the bound components were profiled using SDS-PAGE and mass spectrometry. PLIs, snake venom metalloproteins inhibitor (SVMPI), small serum protein (SSP), heat shock proteins, etc were identified. To identify their toxin targets in D. acutus venom, a reverse separation was conducted by coupling the fractionated S. annularis serum proteins to NHS-agarose beads. Fifteen toxins of five families were captured and identified as follows: PLA2s, metalloproteinases, cysteine-rich secretory proteins, snake venom serine proteinases, and C-type lectins. These discoveries increased our understanding of the capacity and mechanism of the natural neutralization of S. annularis to snake venom. These natural inhibitors are medically significant due to their powerful and broad antidotal activities, which may provide alternative and promising drug candidates for snakebite treatment.

Structure-based virtual screening towards the discovery of novel FOXM1 inhibitors.

Aim: Given the importance of FOXM1 in the treatment of ovarian cancer, we aimed to identify an excellent specific inhibitor and examined its underlying therapeutic effect. Materials & methods: The binding statistics for FDI-6 with FOXM1 were calculated through computer-aided drug design. We selected XST-119 through virtual screening, performed surface plasmon resonance and in vitro cell antiproliferative activity analysis and evaluated its antitumor efficacy in a mouse model. Results: XST-119 had significantly higher affinity for FOXM1 and antiproliferative activity than FDI-6. XST-119 had a definite inhibitory activity in a xenograft mouse model. Conclusion: We identified XST-119, a FOXM1 inhibitor, with better efficacy for treatment of ovarian cancer. FOXM1 binding sites for small molecules are also highlighted, which may provide the foundation for further drug discovery.

[Association of phthalate and polycyclic aromatic hydrocarbon exposure during early pregnancy with premature delivery: A cohort study].

OBJECTIVE: To explore the relationship of the exposure to phthalate esters (PAE) and polycyclic aromatic hydrocarbons (PAH) with clinical premature delivery during early pregnancy. METHODS: We conducted a baseline questionnaire survey among 821 pregnant women undergoing prenatal examination in Hubei Provincial Maternal and Child Health Care Hospital, collected their morning urine samples and followed them up to the outcomes of pregnancy. We quantitatively analyzed 10 PAE and 10 PAH metabolites in the urine samples, followed by Mann-Whitney U test, chi-square test, and logistic regression analysis. RESULTS: The detection rate of the 5 factors exposed to was >80% while that of phthalic acid monobenzyl ester (MBzP) was <50% in PAEs; that of the 5 factors exposed to was >80%, that of 3-hydroxyphene (3-OHPHE) was 86.91% while that of 4-hydroxyphene (4-OHPHE) was <50% in PAHs. Logistic regression analysis showed that the risk of premature delivery was higher in the high MBzP- than in the low MBzP-exposure group (aOR = 2.26, 95% CI: 1.17－4.39). CONCLUSION: High MBzP-exposure may be a risk factor for premature delivery.

Hepatitis B virus X protein promotes vimentin expression via LIM and SH3 domain protein 1 to facilitate epithelial-mesenchymal transition and hepatocarcinogenesis.

BACKGROUND: Hepatitis B virus (HBV) X protein (HBX) has been reported to be responsible for the epithelial-mesenchymal transition (EMT) in HBV-related hepatocellular carcinoma (HCC). Vimentin is an EMT-related molecular marker. However, the importance of vimentin in the pathogenesis of HCC mediated by HBX has not been well determined. METHODS: The expression of vimentin induced by HBX, and the role of LIM and SH3 domain protein 1 (LASP1) in HBX-induced vimentin expression in hepatoma cells were examined by western blot and immunohistochemistry analysis. Both the signal pathways involved in the expression of vimentin, the interaction of HBX with vimentin and LASP1, and the stability of vimentin mediated by LASP1 in HBX-positive cells were assessed by western blot, Co-immunoprecipitation, and GST-pull down assay. The role of vimentin in EMT, proliferation, and migration of HCC cells mediated by HBX and LASP1 were explored with western blot, CCK-8 assay, plate clone formation assay, transwell assay, and wound healing assay. RESULTS: Vimentin expression was increased in both HBX-positive hepatoma cells and HBV-related HCC tissues, and the expression of vimentin was correlated with HBX in HBV-related HCC tissues. Functionally, vimentin was contributed to the EMT, proliferation, and migration of hepatoma cells mediated by HBX. The mechanistic analysis suggested that HBX was able to enhance the expression of vimentin through LASP1. On the one hand, PI3-K, ERK, and STAT3 signal pathways were involved in the upregulation of vimentin mediated by LASP1 in HBX-positive hepatoma cells. On the other hand, HBX could directly interact with vimentin and LASP1, and dependent on LASP1, HBX was capable of promoting the stability of vimentin via protecting it from ubiquitination mediated protein degradation. Besides these, vimentin was involved in the growth and migration of hepatoma cells mediated by LASP1 in HBX-positive hepatoma cells. CONCLUSION: Taken together, these findings demonstrate that, dependent on LASP1, vimentin is crucial for HBX-mediated EMT and hepatocarcinogenesis, and may serve as a potential target for HBV-related HCC treatment. Video abstract.

Diagnostic value of radionuclide in bone metastasis after breast cancer surgery: A protocol of systematic review.

BACKGROUND: The objective of this study is to evaluate the accuracy of radionuclide in diagnosis of bone metastasis (BM) after breast cancer surgery (BCS). METHODS: The electronic databases (Cochrane Library, MEDLINE, EMBASE, Web of Science, CBM, and CNKI) will be systematically and comprehensively searched until June 1, 2020 for eligible studies that reported the diagnosis of radionuclide in BM after BCS. In addition, we will also identify grey literatures, such as conference abstracts, and reference lists of included studies. All process of study identification, data extraction, and study methodological quality evaluation will be performed by 2 independent authors. All divergences will be settled by a third author through discussion. All data analysis will be carried out by RevMan 5.3 software (London, UK). RESULTS: This study will scrutinize the most recent evidence of radionuclide in detection of BM after BCS. CONCLUSION: This study may provide evidence of accuracy of radionuclide in diagnosis of BM following BCS. STUDY REGISTRATION NUMBER: PROSPERO CRD42020187646.

Learning graph in graph convolutional neural networks for robust seizure prediction.

OBJECTIVE: Brain-computer interface (BCI) has demonstrated its effectiveness in epilepsy treatment and control. In a BCI-aided epilepsy treatment system, therapic electrical stimulus is delivered in response to the prediction of upcoming seizure onsets, therefore timely and accurate seizure prediction algorithm plays an important role. However, unlike typical signatures such as slow or sharp waves in ictal periods, the signal patterns in preictal periods are usually subtle, and highly individual-dependent. How to extract effective and robust preictal features is still a challenging problem. APPROACH: Most recently, graph convolutional neural network (GCNN) has demonstrated the strength in the electroencephalogram (EEG) and intracranial electroencephalogram (iEEG) signal modeling, due to its advantages in describing complex relationships among different EEG/iEEG regions. However, current GCNN models are not suitable for seizure prediction. The effectiveness of GCNNs highly relies on prior graphs that describe the underlying relationships in EEG regions. However, due to the complex mechanism of seizure evolution, the underlying relationship in the preictal period can be diverse in different patients, making it almost impossible to build a proper prior graph in general. To deal with this problem, we propose a novel approach to automatically learn a patient-specific graph in a data-driven way, which is called the joint graph structure and representation learning network (JGRN). JGRN constructs a global-local graph convolutional neural network which jointly learns the graph structures and connection weights in a task-related learning process in iEEG signals, thus the learned graph and feature representations can be optimized toward the objective of seizure prediction. MAIN RESULTS: Experimental results show that our JGRN outperforms CNN and GCNN models remarkably, and the improvement is more obvious when preictal features are subtle. SIGNIFICANCE: The proposed approach promises to achieve robust seizure prediction performance and to have the potential to be extended to general problems in brain-computer interfaces.