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Background and Aims: Malignant biliary obstruction is always caused by tumors which are unresectable so that palliative stent placement is conducted for drainage of bile duct tree. Recently, irradiation stent with 125I seeds has been used to improve the stent patency and survival time of patients. We conducted this meta-analysis to evaluate the therapeutic efficacy and safety of biliary stent placement with 125I seeds compared with stent placement alone in patients with malignant biliary obstruction. Methods: We searched Pubmed, Web of Science, ClinicalTrials.gov, Cochrane Library, Embase and CNKI databases for all relevant studies up to 1 May 2020. Patient survival, stent patency, and adverse events were the primary outcome measured. Also, Review Manager 5.3 and Stata/SE15.0 were used to perform the analysis. Results: Eleven randomized controlled trials with a total of 767 patients were included for meta-analysis. Stent combined with 125I seeds showed lower risk of stent occlusion at 3 month (Odds Ratios(OR) = 0.15; 95%CI: 0.05-0.49, P =0.002), 6 month (OR = 0.18; 95%CI: 0.08-0.44, P = 0.0001), 9 month (OR = 0.10; 95%CI: 0.05-0.20, P < 0.00001) and 1 year (OR = 0.15; 95%CI: 0.07-0.31, P < 0.00001) and better mean survival (MD = 125days; 95% CI 91-159 days; P < 0.00001) compared with stent placement alone. Also, reconstructed Kaplan-Meier data demonstrated improved survival in patients treated with stent plus 125I seeds (hazard ratio(HR)= 1.886; 95% CI: 1.609 to 2.210; P < 0.0001) Moreover, our analysis did not show significant difference between the two groups about the risk of adverse events including abdominal pain, hemobilia, pancreatitis, cholangitis and cholecystitis. Conclusion: 125I seeds combined with stent demonstrated superior stent patency and improved survival time compared to stent alone with acceptable complications.

BACKGROUND The efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease (NAFLD) is unknown. AIM To evaluate the efficacy of glucose-lowering drugs dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors in treating NAFLD and to perform a comparison between these treatments. METHODS Electronic databases were systematically searched. The inclusion criteria were: Randomized controlled trials comparing DPP-4 inhibitors, GLP-1 RAs, or SGLT2 inhibitors against placebo or other active glucose-lowering drugs in NAFLD patients, with outcomes of changes in liver enzyme [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] from baseline. RESULTS Nineteen studies were finally included in this meta-analysis. Compared with placebo or other active glucose-lowering drug treatment, treatment with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors all led to a significant decrease in ALT change and AST change from baseline. The difference between the DPP-4 inhibitor and SGLT2 inhibitor groups in ALT change was significant in favor of DPP-4 inhibitor treatment (P < 0.05). The trends of reduction in magnetic resonance imaging proton density fat fraction and visceral fat area changes were also observed in all the novel glucose-lowering agent treatment groups. CONCLUSION Treatment with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors resulted in improvements in serum ALT and AST levels and body fat composition, indicating a beneficial effect in improving liver injury and reducing liver fat in NAFLD patients.

Viral myocarditis (VMC) commonly triggers heart failure, for which no specific treatments are available. This study aims to explore the specific role of long non‐coding RNA (lncRNA) maternally expressed 3 (MEG3) in VMC. A VMC mouse model was induced by Coxsackievirus B3 (CVB3). Then, MEG3 and TNF receptor‐associated factor 6 (TRAF6) were silenced and microRNA‐223 (miR‐223) was over‐expressed in the VMC mice, followed by determination of ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). Dual‐luciferase reporter assay was introduced to test the interaction among MEG3, TRAF6 and miR‐223. Macrophages were isolated from cardiac tissues and bone marrow, and polarization of M1 or M2 macrophages was induced. Then, the expressions of components of NLRP3 inflammatory body (NLRP3, ASC, Caspase‐1), M1 markers (CD86, iNOS and TNF‐α) and M2 markers (CD206, Arginase‐1 and Fizz‐1) were measured following MEG3 silencing. In the VMC mouse model, MEG3 and TRAF6 levels were obviously increased, while miR‐223 expression was significantly reduced. Down‐regulation of MEG3 resulted in the inhibition of TRAF6 by promoting miR‐223. TRAF6 was negatively correlated with miR‐223, but positively correlated with MEG3 expression. Down‐regulations of MEG3 or TRAF6 or up‐regulation of miR‐223 was observed to increase mouse weight, survival rate, LVEF and LVFS, while inhibiting myocarditis and inflammation via the NF‐κB pathway inactivation in VMC mice. Down‐regulation of MEG3 decreased M1 macrophage polarization and elevated M2 macrophage polarization by up‐regulating miR‐223. Collectively, down‐regulation of MEG3 leads to the inhibition of inflammation and induces M2 macrophage polarization via miR‐223/TRAF6/NF‐κB axis, thus alleviating VMC.

Polychlorinated biphenyls (PCBs), as persistent organic pollutants, are environmental endocrine-disrupting chemicals (EDCs). We aim to investigate the effects of prepubertal exposure to PCBs on the reproductive development and expression and regulation of related genes in rats. Female rats were treated with Aroclor-1221 (A-1221) (4 mg/kg/day, 0.4 mg/kg/day) or castor oil daily from postnatal day (PND) 28 for 2 weeks by gavage. Morphological, histological, hormonal, and biochemical parameters were studied. Lower weight and relative weight of hypothalamus, earlier puberty onset, a longer length of the estrous cycle, lower serum estradiol and progesterone levels, accelerated ovarian folliculogenesis, and higher apoptotic index in the ovary were found. The in vitro fertilization study showed a lower fertilization rate and cleavage rate. The genetic study revealed higher expression of Kiss-1 mRNA and lower expression of GnRH mRNA in the hypothalamus and higher expression of AMH mRNA and lower expression of C-myc mRNA in the ovary. These confirmed the reproductive damage of A-1221 in rats.

Background Because the overall prognosis remains dismal for patients with resected pancreatic cancer (PC), we aimed to explore the prognostic impact of examined lymph node (ELN) count on lymph node (LN)-negative pancreatic body/tail ductal adenocarcinoma. Methods Patients' data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database (National Cancer Institute, USA) to investigate the relationship between ELN count and survival outcomes of LN-negative pancreatic body/tail ductal adenocarcinoma. Results A total of 700 patients were included, and the median number of ELNs was 11. The respective 1-, 3-, 5-year overall survival (OS) rates were 75.3%, 37.7%, 30.3%, and the 1-, 3-, 5-year cancer-specific survival (CSS) were 78.3%, 41.7%, 34.5%. The X-tile analysis showed that 14 was the most optimal cutoff for both OS and CSS. Kaplan-Meier survival analysis indicated that patients with ELNs >14 had better OS and CSS than ELNs ≤14. Multivariate Cox analysis showed ELNs ≤14 was an independent risk factor for both OS [hazard ratio (HR), 1.357; 95% confidence interval (CI), 1.080-1.704; P=0.009] and CSS (HR, 1.394; 95% CI, 1.092-1.778; P=0.008). Conclusions ELN count is associated with the survival rate in patients with LN-negative pancreatic body/tail ductal adenocarcinoma. Accurate nodal staging for these patients requires more than 14 ELNs.

Objective The aim of this study was to assess the effectiveness of mindfulness meditation (MM) on anxiety, depression, stress and mindfulness in nursing students. Methods A comprehensive search and screening procedures were conducted to locate all MM interventions implemented with nursing students. For randomized controlled trials (RCTs) in accordance with the inclusion criteria, a search was conducted in PubMed, Embase, Web of Science, Medline, PsycINFO, Cumulative Index to Nursing and Allied Health (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), China Biology Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI) and Wanfang. Databases were retrieved from inception through August 2018. Additional studies were identified through hand searches and Internet searches. Two reviewers collected relevant data of eligible articles according to the data extraction tables. Based on Cochrane Handbook, critical appraisal of the methodological quality was assessed by two other reviewers. An Excel form was used to extract main characteristics of included RCTs. Meta-analysis and trial sequential analysis (TSA) were carried out using software RevMan 5.3 and TSA 0.9. Results Five RCTs with 257 nursing students were included. Only two studies were assessed as high quality and three studies were evaluated as moderate quality. Meta-analysis showed that, comparing with the control group, MM could significantly improve anxiety (SMD = −0.45, 95% CI −0.73 to −0.17, P = 0.001) and stress (SMD = −0.69, 95% CI −0.97 to −0.40, P < 0.001). TSA results confirmed that the outcome of the merger is credible. It could also significantly improve depression level of nursing students after 8 weeks intervention duration (SMD = −0.70, 95% CI −1.14 to −0.26, P = 0.002). However, there was no beneficial effect on depression level of nursing students with 1 week intervention duration (SMD = 0.09, 95% CI −0.42 to 0.59, P = 0.74) and its effects on mindfulness level of nursing students also did not show statistical significance (SMD = 0.37, 95% CI −0.04 to 0.77, P = 0.07). No definitive conclusions were drawn from the TSA. Conclusions The results of this meta-analysis indicated that MM could effectively reduce the level of anxiety and stress of nursing students. TSA confirmed that the results of meta-analysis are credible. For depression, it could also significantly improve depression of nursing students with 8 weeks intervention, but there was no significant effect on nursing students with 1 week intervention duration. There was also no beneficial effect on mindfulness level of nursing students. However, TSA indicated that the accumulated evidence is still inconclusive. We suggest that more well-designed clinical trials with large sample and higher quality would be required in future to draw a definitive conclusion.

This paper presents an extremely rare case of testicular metastasis arising from renal pelvis carcinoma. The testicle is a rare site of clinically detectable tumor metastasis, originating rarely from upper tract urothelial carcinoma (UTUC). There are only two cases concerning UTUC metastasis to the testis available in the literature. In this report, we presented a patient who developed serial testicle, lung, liver and retroperitoneal lymph node metastasis from primary urothelial carcinoma of the renal pelvis within one year after surgery and chemotherapy. In conclusion, for patients with a history of UTUC who present with testicular symptoms, clinicians should be highly alert for the possibility of malignant involvement at this site.

T helper 17 (Th17) cells and related cytokines are important in multiple sclerosis (MS), which have become the new therapeutic targets of MS. In published studies, the effect of interferon-β (IFN-β) on the proportion of Th17 cells and related cytokines in MS patients remains controversial. We did a meta-analysis to assess the role of IFN-β on Th17 cells and related cytokines in MS patients. Compared with control subjects, MS patients with IFN-β treatment had a lower proportion of Th17 cells in CD4+ T cells of peripheral blood [-1.49 (-2.96 to -0.02)], interleukin (IL)-17 level [-1.08 (-1.77 to -0.40)], and IL-23 level [-1.63 (-2.59 to -0.68)] in serum. The results showed that IFN-β can reduce the proportion of Th17 cells, the levels of IL-17 and IL-23 in serum of MS.

Objective To explore whether follicular fluid (FF) concentrations of phthalate metabolites are associated with levels of intrafollicular reproductive hormones in women undergoing in vitro fertilization. Design Cross-sectional study. Setting University-affiliated reproductive medicine center. Patient(s) A total of 194 women each contributed one FF sample at oocyte retrieval. Intervention(s) FF aspirates from individual follicles (≥18 mm in diameter) were collected. We measured eight phthalate metabolites and four ovarian hormones in the FF samples. Main Outcome Measure(s) Per-follicle E2, P, total T, and antimullerian hormone (AMH) concentrations. Result(s) Most phthalate metabolites were highly detected in FF samples. We observed a dose-response relationship between increasing monomethyl phthalate (MMP) tertiles and lower E2, P, and T levels. Women in the third tertile of MMP had decreases of 34.23%, 9.44 ng/L, and 23.28% in E2, P, and T, respectively, compared with women in the first tertile. Tertiles of monoethyl phthalate and the percentage of di(2-ethylhexyl) phthalate) metabolites excreted as mono(2-ethylhexyl) phthalate were inversely associated with P. We also identified a negative relationship between monobenzyl phthalate tertiles and AMH. In addition, positive correlations between some of the phthalate metabolites and ovarian hormones were detected. Conclusion(s) FF concentrations of certain phthalate metabolites were associated with altered levels of intrafollicular reproductive hormones, which raises concern over a potential deleterious effect of environmental phthalate exposure on the endocrine capacity and viability of theca and granulosa cells.

Background Phthalates, which are used as excipients of drugs, have been related to adverse reproductive outcomes. However, the relationships between medication use and phthalate exposure among women undergoing in vitro fertilization (IVF) have not been studied. Objective To investigate the associations between the medication intake and phthalate metabolites in urine and follicular fluid (FF). Method Eight phthalate metabolites were measured in urine and FF samples from 274 women undergoing IVF using liquid chromatography-tandem mass spectrometry. Information on recent medication intake was obtained via interview by trained staff. We constructed generalized linear regression models to examine the associations of medication intake with phthalate metabolite concentrations and dose-response relationships between the number of medicines used and metabolite concentrations in two matrices. Results Four of 10 drugs were used by more than 10% of the participants, including vitamins (23.0%), traditional Chinese medicine (TCM, 22.3%), antioxidants (12.4%) and amoxicillin (10.2%). Participants who had used TCM had 26.0% (95% CI: 0.0, 58.8%), 32.6% (95% CI: 4.2, 68.8%) and 32.3% (95% CI: 2.6, 70.6%) higher urinary mono-n-butyl phthalate (MBP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) concentrations, respectively, than those who had not. Antioxidant intake was associated with a 30.6% (95% CI: −48.5, −6.6%) decrease in the urinary MBP concentration. Compared with non-users, women who reported the use of medicines had 53.2% (95% CI: 2.7, 128.5%) higher concentrations of MMP and a 37.7% (95% CI: −60.7, −1.5%) lower level of MBP in FF, respectively. Conclusion Our data suggest that the intake of some medications may increase phthalate exposure among women undergoing IVF.

Background The testes are suspected target organs of SARS‐CoV‐2. However, the results of studies on the effect of COVID‐19 on male reproduction are controversial. Objective To summarize current research on the effects of COVID‐19 on male reproduction. Methods A systematic review of English literature was performed using PubMed and Ovid Embase up to 18 August 2020. Research articles on the presence of SARS‐CoV‐2 in semen, the effects of the virus on semen parameters and any pathological changes in the testes were evaluated. Results Fourteen studies were included in this review. Six of 176 survivors (3.4%) and 1 of 13 decedents (7.7%) in 2 of 12 studies were positive for viral RNA in semen and testicular tissue, respectively. After stratification of patient groups, we found that the virus was detected in the relatively early stage of infection, 6–16 days after disease onset, in semen from survivors. Two of 3 studies reported that some participants had substandard semen quality after COVID‐19, and 1 study found that COVID‐19 may impair semen quality in a severity‐related manner. Pathological analyses showed that injuries to the seminiferous tubule occurred in all decedents (N = 11). Another study found that orchitic and testis fibrin microthrombi occurred in patients with fatal disease (100%, N = 2). Scrotal discomfort of orchiepididymitis or spermatic cord inflammation has also been reported in COVID‐19 patients. Conclusion Current studies suggest that semen is rarely considered a carrier of SARS‐CoV‐2 genetic material during the infection period but not in the semen of recovered patients. Fatal COVID‐19 may cause testicular structure damage without the presence of virus.

Background At the molecular level, competing endogenous RNAs (ceRNAs) regulate other RNA transcripts by competing for shared microRNAs (miRNA). Notably, miRNAs negatively regulate gene expression at the levels of mRNA stability and translation suppression.MethodsWe measured theexpression of miR-218-5p and RNASEH1-AS1 in clinical lung squamous cell carcinoma tissues using qRT-PCR. In an attempt to explore the roles of miR-218-5p and RNASEH1-AS1 in determining the malignant phenotype of NCI-H520 cells, colony formation and MTT assays were performed to measure cell viability and proliferation, and transwell invasion and wound healing assays were performed to examine cell migration and invasion. A ChIP assay was conducted to confirm the direct binding of POU2F1 to the RNASEH1-AS1 promoter.ResultsIn this investigation, the expression of the lncRNA RNASEH1-AS1 is upregulated in human lung cancer tissues, and it functions as a miRNA sponge for hsa-miR-218-5p in human lung squamous carcinoma cells. The lncRNA RNASEH1-AS1 facilitates the growth and motility of lung squamous carcinoma cells, while miR-218-5p exerts the opposite effects. NET1 and POU2F1 are validated as direct and functional targets of miR-218-5p. The downregulation of miR-218-5p releases the suppression of NET1 and POU2F1. POU2F1 binds directly to the lncRNA-RNASEH1-AS1 promoter and functions as transcription factor to enhance the promoter activity of RNASEH1-AS1.ConclusionsOverall, the positive RNASEH1-AS1/hsa-miR-218-5p/NET1/POU2F1 feedback loop can help us understand the regulatory mechanism underlying the genesis and progression of human lung squamouscarcinoma, possibly providing new biomarkers for its diagnosis and treatment.

Background: This study aims to investigate the association between vitamin D (VD) and lung cancer skin metastasis (LCSM). Methods: The following databases will be retrieved from the beginning to the present of each database without language limitation: PUBMED, EMBASE, Cochrane Library, Web of Science, CBM, and CNKI. The reference lists of included trials and other sources will also be checked. Two researchers will independently undertake literature selection, data collection, and study quality evaluation. We will utilize a fixed or random-effect model to pool the data according to the heterogeneity test. The RevMan 5.3 software will be used to analyze the data and perform meta-analysis. Results: This study will summarize high quality study to explore the association between VD and LCSM. Conclusion: The findings of this study will help to judge whether there is association between VD and LCSM. Ethics and dissemination: No research ethical approval is required in this study, because it will only analyze published data. It is expected to disseminate through a peer-reviewed journal. Study registration: osf.io/ph2au.

Ovary plays an important role in the female reproductive system. The maintenance and regulation of ovarian function are affected by various physical and chemical factors. With the development of industrialization, environmental pollutants have caused great harm to public health. Phthalates, as a class of endocrine-disrupting chemicals (EDCs), are synthesized and used in large quantities as plasticizers due to their chemical properties. They are easily released into environment because of their noncovalent interactions with substances, causing human exposure and possibly impairing ovary. In recent years, more and more attention has been paid to the role of epigenetics in the occurrence and development of diseases. And it is urgent to study the role of methylation, gene imprinting, miRNA, and other epigenetic mechanisms in reproductive toxicology.

BACKGROUND Primary hepatic neuroendocrine tumor (PHNET) is a rare primary liver tumor that remains poorly understood. Here, we explored the clinicopathological characteristics and survival outcomes of PHNET patients. MATERIAL AND METHODS PHNET patients diagnosed between 1988 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled in the cohort. Kaplan-Meier analysis was used to determine the survival outcomes. Multivariable Cox regression models were used to identify the risk factors for overall survival (OS) and disease-specific survival (DSS). RESULTS A total of 291 PHNET patients from the SEER database met the inclusion criteria for analysis. The majority of the patients were female (53.6%), white (77.7%), and married (49.5%). The 1-, 3-, and 5-year OS were 57.1%, 39.4%, and 30.2%, and the 1-, 3-, and 5-year DSS rates were 61.3%, 44.3%, and 36.7%, respectively. Multivariate Cox regression models showed that older age, unmarried status, poor differentiated grade, and no tumor-directed surgery were independent risk factors for poor OS and DSS. CONCLUSIONS Older age, unmarried status, poor differentiated grade, and no tumor-directed surgery were associated with poorer prognosis of PHNET. Surgical resection is an effective and reliable treatment method for patients with PHNET.

Ovarian Cancer (OC) is a highly lethal gynecological cancer which often progresses through acquired resistance against the administered therapy. Cisplatin is a common therapeutic for the treatment of OC patients and therefore it is critical to understand the mechanisms of resistance against this drug. We studied a paired cell line consisting of parental and cisplatin resistant (CR) derivative ES2 OC cells, and found a number of dysregulated lncRNAs, with CHRF being the most significantly upregulated lncRNA in CR ES2 cells. The findings corroborated in human patient samples and CHRF was significantly elevated in OC patients with resistant disease. CHRF was also found to be elevated in patients with liver metastasis. miR-10b was found to be mechanistically involved in CHRF mediated cisplatin resistance. It induced resistance in not only ES2 but also OVCAR and SKOV3 OC cells. Induction of epithelial-to-mesenchymal-transition (EMT) and activation of STAT3 signaling were determined to be the mechanisms underlying the CHRF-miR-10b axis-mediated cisplatin resistance. Down-regulation of CHRF reversed EMT, STAT3 activation and the resulting cisplatin resistance, which could be attenuated by miR-10b. The results were also validated in an in vivo cisplatin resistance model wherein CR cells were associated with increased tumor burden, CHRF downregulation associated with decreased tumor burden and miR-10b again attenuated the CHRF downregulation effects. Our results support a novel role of lncRNA CHRF in cisplatin resistance of OC and establish CHRF-miR-10b signaling as a putative therapeutic target for sensitizing resistant OC cells.

Human umbilical cord mesenchymal stem cell (UC-MSC) application is a promising arising therapy for the treatment of premature ovarian failure (POF). However, little is known about the inflammation regulatory effects of human umbilical cord MSCs (UC-MSCs) on chemotherapy-induced ovarian damage, regardless of in vivo or in vitro. This study was designed to investigate the therapeutic effects of UC-MSC transplantation and underlying mechanisms regarding both apoptosis and inflammation in POF mice. The chemotherapy-induced POF models were induced by intraperitoneal injection of cyclophosphamide. Ovarian function parameters, granulosa cell (GC) apoptosis, and inflammation were examined. Morphological staining showed that UC-MSC treatment increased the ovary size, and the numbers of primary and secondary follicles, but decreased the number of atretic follicles. Estradiol levels in the UC-MSC-treated group were increased while follicle-stimulating hormone levels were reduced compared to those in the POF group. UC-MSCs inhibited cyclophosphamide-induced GC apoptosis and inflammation. Meanwhile, phosphorylation of AKT and P38 was elevated after UC-MSC treatment. Tracking of UC-MSCs in vivo indicated that transplanted UC-MSCs were only located in the interstitium of ovaries rather than in follicles. Importantly, UC-MSC-derived extracellular vesicles protected GCs from alkylating agent-induced apoptosis and inflammation in vitro. Our results suggest that UC-MSC transplantation can reduce ovary injury and improve ovarian function in chemotherapy-induced POF mice through anti-apoptotic and anti-inflammatory effects via a paracrine mechanism.

Signal transducer and activator of transcription 4 (STAT4) has been implicated in the progression of myocarditis. The aim of the current study was to investigate the role by which STAT4 influences autoimmune myocarditis in an attempt to identify a theoretical therapeutic perspective for the condition. After successful establishment of an autoimmune myocarditis rat model, the expression patterns of STAT4, NF-κB pathway-related genes, Th1 inflammatory cytokines (IFN-γ and IL-2), and Th2 inflammatory cytokines (IL-6 and IL-10) were subsequently determined. The rats with autoimmune myocarditis were treated with oe-STAT4 or sh-STAT4 lentiviral vectors to evaluate the role of STAT4 in autoimmune myocarditis, or administrated with 1 mL 10 μmol/L of BAY11-7082 (the NF-κB pathway inhibitor) via tail vein to investigate the effect of the NF-κB pathway on autoimmune myocarditis. Finally, cell apoptosis was evaluated. The serum levels of IFN-γ and IL-2, extent of IκBα and P65 phosphorylation, and the expression of STAT4 were elevated, while the serum levels of IL-6 and IL-10 as well as the expression of IκBα were reduced among the rats with autoimmune myocarditis, which was accompanied by an increase in the apoptotic cells. More importantly, the silencing of STAT4 or the inhibition of the NF-κB pathway was detected to result in a decrease in the serum levels of IFN-γ and IL-2 and an elevation of the serum levels of IL-6 and IL-10, and inhibited myocardial cell apoptosis in rats with autoimmune myocarditis. Moreover, STAT4 silencing was also observed to decrease the extent of IκBα and P65 phosphorylation while acting to elevate the expression of IκBα. Taken together, silencing of STAT4 could hinder the progression of autoimmune myocarditis by balancing the expression of Th1/Th2 inflammatory cytokines via the NF-κB pathway, which may provide a novel target for experimental autoimmune myocarditis (EAM) treatment.

Background and Aims: The best treatment modalities for elderly patients with stage I–II HCC (hepatocellular carcinoma) remain controversial in an era of a shortage of liver donors. Methods: From the SEER database (Surveillance, Epidemiology, and End Results program), 2,371 elderly patients were sampled as Cohort 1. OS (Overall Survival) and CSS (Cancer-Specific Survival) were compared between the Non-surgery and Surgery groups. A stratification analysis in a CSS Cox model was also conducted among sub-groups, and propensity score matching was performed to generate Cohort 2 (746 pairs), reducing the influences of confounders. Results: For Cohort 1, the median follow-up times of the Non-surgery and Surgery groups were 11 months (95% CI, confidence interval: 9.74–12.26) vs. 49 months (44.80–53.21) in OS, and 14 months (12.33–15.67) vs. 74 months (64.74–83.26) in CSS, respectively. In the stratification analysis, for the elderly patients (age >= 70 years), Larger Resection was associated with a higher HR (hazard ratio) than Segmental Resection: 0.30 (95% CI, confidence interval: 0.22–0.41) vs. 0.29 (0.21–0.38) in 70–74 year-olds; 0.26 (0.18–0.38) vs. 0.23 (0.16–0.32) in 75–79 year-olds; 0.32 (0.21–0.49) vs. 0.21 (0.13–0.32) in those 80+ years old. For Cohort 2, a similar result could be seen in the CSS Cox forest plot. The HRs of Larger Resection and Segmental Resection were 0.27 (0.21–0.33) and 0.25 (0.20–0.31), respectively. Conclusions: It is cautiously recommended that, when liver transplantation is not available, segmental or wedge liver resection is the better treatment choice for elderly patients with stage I–II HCC (AJCC edition 6), especially those over 70 years old, compared with other surgeries, based on the SEER data.

Collagen β (1‑O) galactosyltransferase 1 (GLT25D1) has been reported to transfer galactose to hydroxylysine residues via β (1‑O) linkages in collagen. The present study investigated the function of the collagen galactosyltransferase activity of GLT25D1 against carbon tetrachloride (CCl4)‑induced acute liver injury in vitro. Glt25d1+/‑ mice and wild‑type (WT) mice were injected intraperitoneally with the same dose of CCl4. The grade of hepatic injury and the extent of hepatocyte necrosis in the acute phase were assessed 48 h following CCl4 injection. Hepatocyte necrosis was evaluated by histological examination and by serum alanine aminotransferase and aspartate aminotransferase levels, which were higher in the Glt25d1+/‑ mice compared with those in the WT mice. Reverse transcription‑quantitative polymerase chain reaction was performed, and the results demonstrated that the mRNA expression levels of inflammatory cytokines, including tumor necrosis factor‑α and interleukin‑6 were significantly increased in the Glt25d1+/‑ mice. Furthermore, western blot analyses were performed, and the results demonstrated that the protein levels of cleaved caspase‑3 and ‑9 were also markedly increased in the Glt25d1+/‑ liver, indicating that hepatocyte apoptosis was induced. Additionally, the expression levels of transforming growth factor (TGF)‑β1 and phosphorylated small mothers against decapentaplegic (Smad)2 were markedly upregulated, indicating activation of the TGF‑β1/Smad2 signaling pathway during CCl4‑induced acute liver injury in Glt25d1+/‑ mice. CCl4 administration also resulted in severe damage to Glt25d1+/‑ primary hepatocytes in vitro. Taken together, the downregulation of Glt25d1 deteriorated CCl4‑induced liver injury in mice, which may involve triggering inflammatory responses, apoptosis and TGF‑β1/Smad2 signaling pathway activation.

Aim The study aimed to investigate the role of two polymorphisms of methylenetetrahydrofolate reductase (MTHFR), C677T and A1298C, in the risk of potentially malignant oral disorders (PMODs). Materials and methods Genotypes of the MTHFR C677T and A1298C polymorphisms were determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) for 224 PMOD cases and 485 age-matched controls. Results The C677T T allele-carrying genotypes were significantly associated with a decreased risk of PMODs [odds ratio (OR)=0.62, 95% confidence interval (CI)=0.44-0.86]. Haplotype analysis also indicated that the 677T/1298A haplotype was associated with a decreased risk of PMODs (OR=0.56, 95%CI=0.40-0.80). No significant interaction was observed between MTHFR polymorphisms and lifestyle factors. Conclusion Our findings suggest that the T-allele-carrying MTHFR C677T genotype or haplotype may reduce the risk of PMODs. However, these observations require further confirmation using larger samples.

Experimental studies have demonstrated that disinfection byproducts (DBPs) can cause ovarian toxicity including inhibition of antral follicle growth and disruption of steroidogenesis, but there is a paucity of human evidence. We aimed to investigate whether urinary biomarkers of exposure to drinking water DBPs were associated with ovarian reserve. The present study included 956 women attending an infertility clinic in Wuhan, China from December 2018 to January 2020. Antral follicle count (AFC), ovarian volume (OV), anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH) were measured as indicators of ovarian reserve. Urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were assessed as potential biomarkers of drinking water DBP exposures. Multivariate linear and Poisson regression models were applied to estimate the associations of urinary DCAA and TCAA concentrations with indicators of ovarian reserve. Elevated urinary DCAA and TCAA levels were monotonically associated with reduced total AFC (− 5.98%; 95% CI: − 10.30%, − 1.44% in DCAA and − 12.98%; 95% CI: − 17.00%, − 8.76% in TCAA comparing the extreme tertiles; both P for trends ≤ 0.01), and the former was only observed in right AFC but not in left AFC, whereas the latter was estimated for both right and left AFC. Moreover, elevated urinary TCAA levels were monotonically associated with decreased AMH (− 14.09%; 95% CI: − 24.79%, − 1.86% comparing the extreme tertiles; P for trend = 0.03). These negative associations were still observed for the exposure biomarkers modeled as continuous variables. Our findings suggest that exposure to drinking water DBPs may be associated with decreased ovarian reserve.

The best time window of percutaneous coronary intervention (PCI) is within 12 hours for ST-segment elevation myocardial infarction (STEMI). However, there is limited evidence about the proper time of PCI for delayed STEMI patients.From June 2014 to June 2015, a total of 268 patients receiving PCI with second-generation drug-eluting stent in a Chinese hospital after 3 days of STEMI onset were enrolled in this retrospective study, who were divided into the early group (3-14 days) and the late group (>14 days). A propensity score match was conducted to reduce the baseline difference. The primary endpoint of all-cause death and secondary endpoints of major adverse cardiac and cerebrovascular event (myocardial infarction [MI], stroke, emergent revascularization, and rehospitalization due to heart failure) were compared using survival analysis.At last, 182 cases were matched after propensity score match, with no statistical difference in baseline characteristics and PCI data. Kaplan-Meier survival curve demonstrated no difference in all-cause death of the 2 groups (P = .512). However, the early group presented a higher incidence of MI than the late group (P = .036). The multivariate Cox regression analysis also demonstrated that the early PCI was an independent risk factor for MI compared with late PCI (hazard ratio = 3.83, 95%CI [1.91-8.82], P = .001). There was no statistical difference in other major adverse cardiac and cerebrovascular event, including stroke, emergent revascularization, and rehospitalization due to heart failure.Using the 2nd drug-eluting stent, early PCI (3-14 days) and late PCI (>14 days) have comparable efficacy and outcomes. However, patients receiving early PCI are subjected to a relatively higher risk of recurrent MI.

The increased levels of intracellular reactive oxygen species (ROS) in granulosa cells (GCs) may affect the pregnancy results in women with polycystic ovary syndrome (PCOS). In this study, we compared the in vitro fertilization and embryo transfer (IVF-ET) results of 22 patients with PCOS and 25 patients with tubal factor infertility and detected the ROS levels in the GCs of these two groups. Results showed that the PCOS group had significantly larger follicles on the administration day for human chorionic gonadotropin than the tubal factor group (P0.05); however, the number of retrieved oocytes was not significantly different between the two groups (P0.05). PCOS group had slightly lower fertilization, cleavage, grade I/II embryo, clinical pregnancy, and implantation rates and higher miscarriage rate than the tubal factor group (P0.05). We further found a significantly higher ROS level of GCs in the PCOS group than in the tubal factor group (P0.05). The increased ROS levels in GCs caused GC apoptosis, whereas NADPH oxidase 2 (NOX2) specific inhibitors (diphenyleneiodonium and apocynin) significantly reduced the ROS production in the PCOS group. In conclusion, the increased ROS expression levels in PCOS GCs greatly induced cell apoptosis, which further affected the oocyte quality and reduced the positive IVF-ET pregnancy results of women with PCOS. NADPH oxidase pathway may be involved in the mechanism of ROS production in GCs of women with PCOS.

Background In molecular level, competing endogenous RNAs (ceRNAs) regulates other RNA transcripts through competing for shared microRNAs (miRNA). miRNA negatively regulate gene expression at the levels of mRNAs stability and translation suppression. Methods We tested the mRNA level of miR-218-5p and RNASEH1-AS1 in clinical lung squamous cell carcinoma tissues by qRT-PCR. In the exploring of the role of miR-218-5p and RNASEH1-AS1 in the malignant phenotype of NCI-H520 cells, colony formation and MTT assay were used to test the cell viability and proliferation capability, trans-well invasion and wound healing assay were performed to examine the cell migration and invasion. ChIP assay was conducted to confirm the direct interact of POU2F1 and RNASEH1-AS1 promoter. Results In this investigation, we found that LncRNA RNASEH1-AS1 is up-regulated in human lung cancer, and serves as a miRNA sponge for hsa-miR-218-5p in human lung squamous carcinoma cells. lncRNA RNASEH1-AS1 facilitates growth and motility of lung squamous carcinoma cells, while miR-218-5p does the opposite. NET1 and POU2F1 are validated as direct and functional targets of miR-218-5p. The downregulation of miR-218-5p releases the suppression of NET1 and POU2F1. POU2F1 binds directly to the lncRNA-RNASEH1-AS1 promoter and acts as transcription factor to enhance the promoter activity of RNASEH1-AS1. Conclusion Above all, the positive feedback loop of RNASEH1-AS1/ hsa-miR-218-5p/ NET1/ POU2F1 can help us to understand the regulatory mechanism behind genesis and progression of human lung squamous carcinoma, possibly providing new biomarkers for its diagnosis and treatment.

AIM Our aim was to investigate associations between blastocyst morphology parameters and live birth outcome and to make possible additional recommendations for existing embryo selection strategies. METHODS This retrospective cohort study included 2593 frozen-thawed single blastocyst transfers (SBT) cycles from 2012 to 2016. Multivariable logistic regression model was used to analyze the independent predictive effectiveness of blastocyst parameters for live birth rate (LBR). RESULTS The participants enrolled in the present study were 32 (28-35) years old with a median body mass index of 21.20 (19.60-23.40) kg/m2 , among whom 1058 (40.8%) women had live births. Among the three blastocyst morphology parameters, we found only inner cell mass grade and trophectoderm cell grade had significant effects on LBR (P

Using the first coherent elastic neutrino-nucleus scattering data, we determine the average neutron root-mean-square (rms) radius of $^{133}\rm{Cs}$ and $^{127}\rm{I}$. A model-independent value $R_{n}=5.5{}^{+0.9}_{-1.1}\,\rm{fm}$ is obtained using the symmetrized Fermi and Helm form factors. Meanwhile, the nuclear structure suppression of the full coherence is observed with a significance of $2.3\sigma$.

Homoharringtonine (HHT) and imatinib have a synergistic effect in the clinical treatment of chronic myeloid leukemia (CML). The purpose of the present study was to explore the underlying mechanisms by which HHT enhanced imatinib sensitivity. K562 CML cells were treated with HHT and imatinib separately or in combination. Cell viability was detected by Cell Counting Kit‑8 assay; apoptotic rates and protein expression levels of phosphorylated‑tyrosine (p‑Tyr) and p‑CRK like proto‑oncogene, adaptor protein (p‑Crkl) were analyzed by flow cytometry; zinc‑finger protein, X‑linked (ZFX) overexpression plasmid was transfected to cells using electroporation; western blotting was used to detect the protein expression levels of PI3K, AKT, p‑AKT and ZFX; and reverse transcription‑quantitative PCR was used to measure ZFX mRNA expression levels. The results demonstrated that HHT and imatinib co‑treatment had significant effects of proliferation inhibition and apoptosis induction on K562 CML cells compared with imatinib alone. Co‑treatment also significantly downregulated the expression levels of p‑Tyr, p‑Crkl, PI3K and p‑Akt compared with imatinib or HHT treatment. In addition, HHT downregulated ZFX mRNA and protein expression. ZFX overexpression reversed cell sensitivity to imatinib and HHT and also reduced the HHT‑induced imatinib sensitization by increasing p‑Akt expression. In conclusion, HHT may enhance the effect of imatinib on CML cells by downregulating ZFX.

Systemic lupus erythematosus (SLE) is a multisystem disease with protean manifestations. Lupus pancreatitis is the second most common disease associated with SLE-related acute abdomen. Although acute pancreatitis is rare it is clinically important because this condition can be life threatening if not treated promptly. Here, we report a case of a 10-year-old girl who developed SLE-associated pancreatitis after steroids therapy that was subsequently complicated by fungal septicaemia. Her clinical symptoms and signs markedly improved after administration of glucocorticoids and cyclophosphamide.El lupus eritematoso sistémico (LES) es una enfermedad multisistémica con manifestaciones proteicas. La pancreatitis lúpica es la segunda enfermedad más frecuentemente asociada con el abdomen agudo en relación con el LES. Si bien la pancreatitis aguda es rara, es clínicamente importante porque puede ser potencialmente mortal si no se trata de inmediato. En este artículo, describimos el caso de una niña de 10 años que desarrolló pancreatitis asociada a LES después del tratamiento con corticoesteroides que se complicó posteriormente debido a septicemia fúngica. Los signos y síntomas clínicos mejoraron marcadamente después de la administración de glucocorticoides y ciclofosfamida.

Phthalate exposure was reported to induce defects in ovarian function, and further influence embryo development and pregnancy outcomes. However, the data about the associations of phthalates with intermediate and pregnancy outcomes of in vitro fertilization (IVF) cycles are scarce in the Chinese population.A total of 663 women receiving IVF/intracytoplasmic sperm injection (ICSI) treatments in our center were enrolled in this analysis. They provided one urine sample on the day of oocyte retrieval. We measured urinary concentrations of eight phthalate metabolites. Generalized linear models were used to analyze the associations of urinary phthalate metabolites with ovarian response, fertilization, early embryo development, and pregnancy outcomes.Among all the phthalate metabolites, mono-n-butyl phthalate (MBP) had the highest urinary concentration with a median level of 101.51 μg/g creatinine (Cr). MBP concentration was inversely associated with normal fertilization odds (overall P-trend 0.01). There was a significant correlation of monoethyl phthalate (MEP) with decreased odds of normal fertilization in medium-concentration group compared to low-concentration group (overall P-trend = 0.02). No significant associations of metabolite concentrations with the odds of good-quality embryos on day 3 or blastocyst formation were found. Monomethyl phthalate (MMP) and MEP in medium-concentration group reduced 22.4% (95% CI: 0.64-0.94, overall P-trend = 0.04) and 21.9% (95% CI: 0.64-0.95, overall P-trend = 0.05) of the odds to gain good-quality blastocyst compared to low-concentration group. The eight phthalate metabolites were not correlated to clinical pregnancy rate, live birth rate, or early miscarriage rate. There was no significant association of di (2-ethylhexyl) phthalate (DEHP) metabolites observed with any clinical outcomes in the total population. After excluding male infertility, mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) in medium-concentration group turned to be associated with a higher number of retrieved oocytes (overall P-trend = 0.04), whereas mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) in medium-concentration group was associated with a lower odds of normal fertilization compared to low-concentration group (overall P-trend = 0.02).Urinary MBP concentration was much higher compared to other phthalate metabolites in this cohort of Chinese IVF/ICSI women, and also higher than it was reported by studies in other countries. MBP showed adverse impacts on fertilization. MMP and MEP could affect blastocyst quality, but not embryo quality on day 3. DEHP metabolites didn't show consistent reproductive toxicities as demonstrated in previous studies.

A Fe(III)-promoted highly selective photo-oxidation of benzylic C–H bond delivering relative carbonyl products is reported. By altering the concentration of ferric salt, methylarenes can be selectively oxidized under UV irradiation to furnish aromatic aldehydes or acids, respectively. By this protocol, the oxidation of ethylarenes provides the corresponding acetophenones. The reaction is inferred to involve divergent pathways in different concentrations of catalyst for the alternative selectivity between aldehydes and aicds. The reusable catalyst, high conversion and selectivity make this oxidation a green and economic protocol for the synthesis of aromatic carbonyl compounds.

// Qian Wang 1 , Wei Ding 1 , Yihan Ding 1 , Jingjing Ma 1 , Zhaoye Qian 2 , Jingxian Shao 2 and Yufeng Li 1 1 Department of Hematology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, 223300, China 2 Department of Oncology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, 223300, China Correspondence to: Yufeng Li, email: liyufeng99@netease.com Keywords: Bcl-6/p53 pathway, homoharringtonine, imatinib, drug-resistance, chronic myeloid leukemia Received: March 04, 2016 Accepted: March 08, 2017 Published: March 30, 2017 ABSTRACT Background: The anti-leukemic mechanism of homoharringtonine (HHT) differs from that of IM, and HHT is one of the most useful agents for use in patients with IM resistance or intolerance. The Bcl-6/p53 pathway has been shown to regulate the sensitivity of tumor cells to antitumor drugs. We tested whether HHT blocked the Bcl-6/p53 pathway in order to promote the apoptosis of IM-resistant cells in vitro and in vivo . Results: Ph+ acute lymphoblastic leukemia (ALL) cells and IM-resistant chronic myeloid leukemia (CML) cells showed high expression of Bcl-6 protein. Bcl-6 mediated the upregulation of p53, and and Bcl-6 induced growth inhibition of IM-resistant cells as well as its apoptosis by targeting p53. In addition, Bcl-6 was downregulated moderately after HHT treatment in different cells. The Bcl-6 expression was significantly increased in patients with CML when compared with healthy subjects. Furthermore, the expression of Bcl-6 was higher in patients with CML-blastic phase (CML-BP) than in those with CML-chronic phase (CML-CP). Methods: The inhibitory effect of drugs on cell growth was detected by Cell Counting Kit-8 (CCK-8), The apoptosis rate and the cell cycle were investigated by flow cytometry. The expression of Bcl-6, p53, Bcl-2, caspase9, and caspase3 proteins was assayed by western blot, Real- Time PCR (qPCR) detect Bcl-6 and p53 mRNA. Conclusions: HHT can suppress the growth and induce apoptosis of IM-resistant cells, the mechanism of which is associated with blocking of the Bcl-6/p53 pathway. Our results could offer a theoretical explanation for HHT use in patients with IM resistance or intolerance.

In this study, a printable GO ink was prepared by dispersing 120 mg GO in 30 ml mixed solvents (deionized water : ethanol : ethylene glycol = 1 : 1 : 1). The prepared ink was inkjet-printed onto the flexible substrate PET. Printed patterns were reduced with intense pulsed light (IPL) without damaging the substrate PET. By adjusting the distance between the intense light and the patterns and number of pulses in a given time, patterns with low resistance and good flexibility were achieved. Upon printing 20 passes, the resistance decreased from 56.77 MΩ for the patterns before IPL treatment to 760.4 Ω for the patterns after IPL treatment. It was lowered by nearly four orders of magnitude. It was proved that IPL reduction on the GO ink could be used as an effective method for the synthesis of flexible electronics such as sensors.

Exposure to phthalates has been demonstrated to cause reproductive toxicity in animals, but evidence of the association between phthalates and markers of male reproductive function have been inconsistent in human studies. Here we examined whether environmental exposure to phthalates contributes to altered reproductive hormone levels, sperm DNA damage and spermatozoa apoptosis in a Chinese population. From March to June 2013, repeated urine samples collected from male partners of couples attending an infertility clinic in Wuhan, China were analyzed for 8 phthalate metabolites. Associations of the urinary phthalate metabolites with serum hormone levels (n=483), sperm DNA damage parameters (n=509) and spermatozoa apoptosis measures (n=467) were assessed using multivariable linear regression models. After adjusting for potential confounders, mono-(2-ethylhexyl) phthalate (MEHP), a metabolite of di-(2-ethylhexyl)-phthalate (DEHP), was inversely associated with serum levels of estradiol, total testosterone (T) and free T (all P for trend

Evidence from toxicological studies has demonstrated that phthalates can lead to reduced fertility through effects on folliculogenesis, oocyte maturation and embryonic development, but human data are limited. Concentrations of eight phthalate metabolites in 110 follicular fluid (FF) and urine samples collected from 112 women attending an infertility clinic in Wuhan, China were quantified, and correlations between paired matrices were explored. Associations between metabolite concentrations and in vitro fertilization (IVF) parameters were evaluated with multivariable models. Six metabolites were detected in >72.73% of the FF samples. MEHP and MBP were the dominant metabolites with a median level of 2.80 and 2.05ng/mL, respectively. Significant correlations between the two matrices, urine and FF, were found for MEP (rs=0.44), and MBP (rs=0.22). FF and urinary metabolite concentrations were not associated with any IVF parameters. However, given the prevalence of phthalates exposure, further work is needed to elucidate the potential hazard on female reproduction.

Objective To investigate the vertical transmission of hepatitis B virus (HBV) via embryos to children and whether HBV in embryos has an effect on the development of the fetus and pregnancy outcomes of in vitro fertilization and embryo transfer (IVF-ET). Design Long-term follow-up study. Setting Research laboratory. Patient(s) Thirty-one couples with a hepatitis B surface antigen (HBsAg)-negative woman and HBsAg-positive man, and 41 couples with a HBsAg-positive woman and HBsAg-negative man, whose unfertilized oocytes and nonviable embryos were tested for HBV DNA, RNA, or HBsAg. Intervention(s) HBV DNA, RNA, or HBsAg analyses in unfertilized oocytes and nonviable embryos. Main Outcome Measure(s) HBV serologic markers analyses. Result(s) We obtained follow-up data for 71 couples. A total of 24 babies were born, and no newborns exhibited defects at birth. Twelve babies were born to couples with HBV-positive oocytes and/or embryos. The pregnancy outcomes were not associated with the presence of HBV in oocytes and embryos. Three patterns of HBV serologic markers were screened. Twenty babies were anti-HBs-positive. Three babies were negative for HBsAg, antibody to hepatitis B surface antigen (anti-HBs), antibody to hepatitis B core antigen (anti-HBc), HBeAg, and antibody to hepatitis B e antigen (anti-HBe). One baby was seropositive for anti-HBs, anti-HBc, and anti-HBe at 6 months of age but seroconverted from anti-HBe-positive to anti-HBe-negative at 9 months of age. Conclusion(s) The presence of HBsAg in oocytes and embryos may not result in the vertical transmission of HBV in the offspring of HBV carriers.

Exposure to phthalates has been found to have adverse effects on male reproductive function in animals. However, the findings from human studies are inconsistent. Here we examined the associations of phthalate exposure with semen quality and reproductive hormones in a Chinese population using phthalate metabolite concentrations measured in semen as biomarkers. Semen (n = 687) and blood samples (n = 342) were collected from the male partners of sub-fertile couples who presented to the Reproductive Center of Tongji Hospital in Wuhan, China. Semen quality parameters and serum reproductive hormone levels were determined. Semen concentrations of 8 phthalate metabolites were assessed using high-performance liquid chromatography and tandem mass spectrometry. Associations of the semen phthalate metabolites with semen quality parameters and serum reproductive hormones were assessed using confounder-adjusted linear and logistic regression models. Semen phthalate metabolites were significantly associated with decreases in semen volume [mono-n-butyl phthalate (MBP), mono-(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)], sperm curvilinear velocity [monobenzyl phthalate (MBzP), MEHP, the percentage of di-(2-ethylhexyl)-phthalate metabolites excreted as MEHP (%MEHP)], and straight-line velocity (MBzP, MEHP, %MEHP), and also associated with an increased percentage of abnormal heads and tails (MBzP) (all p for trend

Exposure to phthalates during gestation has been associated with decreased birth weight among offspring. However, the associations between preconception phthalate metabolites in follicular fluid (FF) and offspring birth weight among women undergoing in vitro fertilization (IVF) remain largely unknown. Here, we explored the associations between preconception phthalate metabolite concentrations in FF and the birth weights of singletons and twins among women undergoing IVF. We recruited 147 female participants who gave birth to 90 singletons and 57 twin infants at the Reproductive Medicine Center, Tongji Hospital, Wuhan, between November and December 2016. Each participant was asked to complete a questionnaire at the time of recruitment and provide a FF sample on the day of oocyte retrieval. The FF concentrations of eight phthalate metabolites were determined using high-performance liquid chromatography and tandem mass spectrometry. Birth outcomes were abstracted from medical records. The associations between phthalate metabolites in FF and birth weights of the singleton and twin groups were evaluated using generalized linear models (GLMs). We found that birth weight in the twin group had negative dose-response associations with maternal preconception monobenzyl phthalate (MBzP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) in FF (both P for trends0.05) and that birth weight in the singleton group had positive dose-response associations with monoethyl phthalate (MEP) and mono(2-ethyl-5 hydroxyhexyl) phthalate (MEHHP) in FF (both P for trends0.05). These associations persisted when we modeled as continuous variables. In addition, we observed male-specific association between decreased twin birth weight and MEOHP and MBzP and a female-specific associations between increased singleton birth weight and MEP, MEHHP and the sum of di(2-ethylhexyl) phthalate (∑DEHP) (all P for interactions0.05). Preconception phthalate metabolites in maternal FF may affect the birth weights of both singleton and twin newborns.

Epidemiological studies have suggested that phthalate exposures were associated with adverse reproductive outcomes, such as low oocyte yield and reduced embryo quality, but the underlying mechanisms remained largely unknown. Oxidative stress may be a potential contributor to phthalate-induced adverse reproductive outcomes. To explore the associations between phthalate exposure and levels of oxidative stress among women seeking in vitro fertilization (IVF), we measured the concentrations of eight phthalate metabolites and biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and total antioxidant capacity (TAC), in follicular fluid (FF) samples collected from 332 women. Multivariable linear regression models were used to assess the associations between phthalate metabolites and biomarkers of oxidative stress in FF samples. The concentrations of most tested phthalate metabolites were positively associated with the 8-OHdG levels. The metabolites of di-(2-ethylhexyl) phthalate (DEHP) were inversely associated with the TAC levels. The concentrations of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) were positively associated with the MDA levels. Our results revealed a positive association between phthalate metabolites and oxidative stress levels in FF, while more toxicological and epidemiological studies are required to confirm our findings.

Background Phthalate metabolites in follicular fluid (FF) may negatively affect normal folliculogenesis; however, the predictors of phthalate metabolite concentrations in urine and FF and relationships between urine and FF phthalate metabolite concentrations among women undergoing in vitro fertilization (IVF) are poorly understood. Objective To investigate predictors of phthalate metabolites in urine and FF and correlations between urine and FF phthalate metabolite concentrations among women undergoing IVF. Method We recruited 305 women seeking infertility treatment at a reproductive center in Wuhan, China, from October to November 2016. Information regarding demographic characteristics, personal care product use and plastic material contact was obtained through direct interviews. Concentrations of 8 phthalate metabolites in urine and FF samples were measured using high-performance liquid chromatography and tandem mass spectrometry. Associations regarding metabolite concentrations in urine and FF samples were analysed by Spearman's correlation and linear regression. Generalized linear regression was used to examine potential predictors of phthalate metabolite concentrations in urine and FF. Results Weak to moderate associations between urine and FF samples were found for monoethyl phthalate (MEP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) (correlation coefficient: MEP, 0.350; MEOHP, 0.377); no associations were observed for other metabolites. The predictive powers of urinary metabolite concentrations in determining FF metabolite concentrations were uniformly low, with R2 ≤ 0.113. Body mass index (BMI) and educational level were inversely associated with the urinary concentrations of certain metabolites. Higher household income, intake of bottled drinks within 48 h, and use of shower gel and soap were frequently associated with higher urinary metabolite concentrations. BMI, higher household income and use of disposable plastic cups within 48 h were associated with higher metabolite concentrations in FF. Conclusion Phthalate metabolite concentrations in urine and FF vary according to sociodemographic characteristics and lifestyle factors. Phthalate metabolite concentrations in urine may not be appropriate for estimating ovary phthalate exposure.

Continuous improvement in diagnosis and treatment has significantly increased the survival of cancer patients. Treatments for neoplastic disease, including radiotherapy, chemotherapy, and surgery or combined therapy with the above methods, may lead to premature ovarian insufficiency (POI) or substantial male germ cell loss. For the patients it is a seriously double whammy. Therefore, reproductive medicine experts strongly suggest that all young patients diagnosed with a malignant tumor should immediately undergo a consultation with suggestions for fertility and endocrine function protection and preservation. Here, we discuss the background knowledge, methods, indications, pros and cons, and experimental and clinical applications of fertility preservation, and new strategies for future fertility conservation to help physicians, especially oncologist, pediatrician, hematologist, and surgeons, become aware of the concepts, methods, and importance of fertility and endocrine function protection. We also hope to help doctors develop novel personalized strategies for fertility conservation according to patients' own conditions, tumor types, treatment methods, recurrence rate and so on. This review focuses on changing and enhancing the fertility preservation idea, further investigations in clinical and translational medicine will help ensure the development of novel personalized treatments, to help cancer patients have healthy children or maintain endocrine function once they are in remission. This is just the ultimate dream of oncofertility.