Knockdown of YTHDF2 initiates ERS-induced apoptosis and cancer stemness suppression by sustaining GLI2 stability in cervical cancer.

Cervical cancer ranks fourth in women in terms of incidence and mortality. The RNA-binding protein YTH N6-methyladenosine RNA-binding protein F2 (YTHDF2) contributes to cancer progression by incompletely understood mechanisms. We show how YTHDF2 controls the fate of cervical cancer cells and whether YTHDF2 could be a valid target for the therapy of cervical cancer. Sphere formation and alkaline phosphatase staining assays were performed to evaluate tumor stemness of cervical cancer cells following YTHDF2 knockdown. Apoptosis was detected by flow cytometry and TUNEL assay. The compounds 4PBA and SP600125 were used to investigate the correlation between JNK, endoplasmic reticulum stress, tumor stemness, and apoptosis. Data from The Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) revealed that GLI family zinc finger 2 (GLI2) might be the target of YTHDF2. The transcription inhibitor actinomycin D and dual-luciferase reporter gene assays were employed to investigate the association between the GLI2 mRNA and YTHDF2. Nude mouse xenografts were generated to assess the effects of YTHDF2 knockdown on cervical cancer growth in vivo. Knockdown of YTHDF2 up-regulated the expression of GLI2, leading to JNK phosphorylation and endoplasmic reticulum stress. These processes inhibited the proliferation of cervical cancer cells and their tumor cell stemness and promotion of apoptosis. In conclusion, the knockdown of YTHDF2 significantly affects the progression of cervical cancer cells, making it a potential target for treating cervical cancer.

Efficacy and safety of endoscopic retrograde cholangiopancreatography in recurrent pancreatitis of pediatric asparaginase-associated pancreatitis.

BACKGROUND: Asparaginase (ASP) is an important drug in combined chemotherapy regimens for pediatric acute lymphoblastic leukemia (ALL); ASP-associated pancreatitis (AAP) is the main adverse reaction of ASP. Recurrent pancreatitis is a complication of AAP, for which medication is ineffective. AIM: To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in treating recurrent pancreatitis due to AAP. METHODS: From May 2018 to August 2021, ten children (five males and five females; age range: 4-13 years) with AAP were treated using ERCP due to recurrent pancreatitis. Clinical data of the ten children were collected, including their sex, age, weight, ALL risk grading, clinical symptoms at the onset of pancreatitis, time from the first pancreatitis onset to ERCP, ERCP operation status, and postoperative complications. The symptomatic relief, weight change, and number of pancreatitis onsets before and after ERCP were compared. RESULTS: The preoperative symptoms were abdominal pain, vomiting, inability to eat, weight loss of 2-7 kg, and 2-9 pancreatitis onsets. After the operation, nine of ten patients did not develop pancreatitis, had no abdominal pain, could eat normally; the remaining patient developed three pancreatitis onsets due to the continuous administration of ASP, but eating was not affected. The postoperative weight gain was 1.5-8 kg. There was one case of post ERCP pancreatitis and two cases of postoperative infections; all recovered after medication. CONCLUSION: ERCP improved clinical symptoms and reduced the incidence of pancreatitis, and was shown to be a safe and effective method for improving the management of recurrent pancreatitis due to AAP.

Repression of rRNA gene transcription by endothelial SPEN deficiency normalizes tumor vasculature via nucleolar stress.

Human cancers induce a chaotic, dysfunctional vasculature that promotes tumor growth and blunts most current therapies; however, the mechanisms underlying the induction of a dysfunctional vasculature have been unclear. Here, we show that split end (SPEN), a transcription repressor, coordinates rRNA synthesis in endothelial cells (ECs) and is required for physiological and tumor angiogenesis. SPEN deficiency attenuated EC proliferation and blunted retinal angiogenesis, which was attributed to p53 activation. Furthermore, SPEN knockdown activated p53 by upregulating noncoding promoter RNA (pRNA), which represses rRNA transcription and triggers p53-mediated nucleolar stress. In human cancer biopsies, a low endothelial SPEN level correlated with extended overall survival. In mice, endothelial SPEN deficiency compromised rRNA expression and repressed tumor growth and metastasis by normalizing tumor vessels, and this was abrogated by p53 haploinsufficiency. rRNA gene transcription is driven by RNA polymerase I (RNPI). We found that CX-5461, an RNPI inhibitor, recapitulated the effect of Spen ablation on tumor vessel normalization and combining CX-5461 with cisplatin substantially improved the efficacy of treating tumors in mice. Together, these results demonstrate that SPEN is required for angiogenesis by repressing pRNA to enable rRNA gene transcription and ribosomal biogenesis and that RNPI represents a target for tumor vessel normalization therapy of cancer.

Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy.

OBJECTIVE: To investigate the role of H+ /K+ ATPase in the proliferation of pepsin-induced vocal cord leukoplakia (VCL) cells. STUDY DESIGN: Translation research. SETTING: Affiliated Hospital of University. METHODS: Immunohistochemistry was used to detect pepsin, H+ /K+ ATPase (ATP4A and ATP4B subunits) in VCL cells with varying degrees of dysplasia. After primary cultures of VCL cells had been established, the effects of acidified pepsin on the proliferation, autophagy, and H+ /K+ -ATPase distribution of VCL cells were investigated. RESULTS: The levels of pepsin, ATP4A, and ATP4B were significantly higher in VCL tissue with moderate-to-severe dysplasia than in normal tissue (p < .05); these levels gradually increased according to dysplasia severity. The expression levels of ATP4A and ATP4B were significantly correlated with the amount of pepsin in VCL cells (p < .01). Acidified pepsin enhanced the levels of proliferation and autophagy in human VCL epithelial cells. The cloning- and autophagy-promoting effects of acidified pepsin on VCL cells were partially reversed by pantoprazole; these effects were completely blocked by the autophagy inhibitor chloroquine. Finally, acidified pepsin promoted the colocalization of H+ /K+ -ATPase and lysosomes in VCL cells; it also mediated lysosome acidification. CONCLUSION: Pepsin and H+ /K+ -ATPase may contribute to the progression of VCL. Specifically, acidified pepsin may regulate lysosome acidification by promoting lysosomal localization of H+ /K+ -ATPase.

External use of mirabilite to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in children: A multicenter randomized controlled trial.

BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Currently, there is no suitable treatment for post-ERCP pancreatitis (PEP) prophylaxis. Few studies have prospectively evaluated interventions to prevent PEP in children. AIM: To assess the efficacy and safety of the external use of mirabilite to prevent PEP in children. METHODS: This multicenter, randomized controlled clinical trial enrolled patients with chronic pancreatitis scheduled for ERCP according to eligibility criteria. Patients were randomly divided into the external use of mirabilite group (external use of mirabilite in a bag on the projected abdominal area within 30 min before ERCP) and blank group. The primary outcome was the incidence of PEP. The secondary outcomes included the severity of PEP, abdominal pain scores, levels of serum inflammatory markers [tumor necrosis factor-alpha (TNF-α) and serum interleukin-10 (IL-10)], and intestinal barrier function markers [diamine oxidase (DAO), D-lactic acid, and endotoxin]. Additionally, the side effects of topical mirabilite were investigated. RESULTS: A total of 234 patients were enrolled, including 117 in the external use of mirabilite group and the other 117 in the blank group. The pre-procedure and procedure-related factors were not significantly different between the two groups. The incidence of PEP in the external use of mirabilite group was significantly lower than that in the blank group (7.7% vs 26.5%, P < 0.001). The severity of PEP decreased in the mirabilite group (P = 0.023). At 24 h after the procedure, the visual analog scale score in the external use of mirabilite group was lower than that in the blank group (P = 0.001). Compared with those in the blank group, the TNF-α expressions were significantly lower and the IL-10 expressions were significantly higher at 24 h after the procedure in the external use of mirabilite group (P = 0.032 and P = 0.011, respectively). There were no significant differences in serum DAO, D-lactic acid, and endotoxin levels before and after ERCP between the two groups. No adverse effects of mirabilite were observed. CONCLUSION: External use of mirabilite reduced the PEP occurrence. It significantly alleviated post-procedural pain and reduced inflammatory response. Our results favor the external use of mirabilite to prevent PEP in children.

Biotransformation and bioaccessibility of active ingredients from Radix Astragali by Poria cocos during solid-state fermentation and in vitro digestion and antioxidant activity evaluation.

Radix Astragali is one of the most famous and frequently used health food supplements and herbal medicines. Among more than 227 components of Radix Astragali, Astragaloside IV (AG IV) is famous functional compound and is commonly used as a quality marker for Radix Astragali. However, the relatively low content of AG IV in Radix Astragali (< 0.04%, w/w) severely limits its application. The purpose of this study is to improve the biotransformation of AG IV and its bioaccessibility during in vitro digestion by Poria cocos solid fermenting Radix Astragali. The optimum fermentation conditions were as follows: Inoculation amount 8 mL; fermentation time 10 d; fermentation humidity 90%. Through fermentation, the content of AG IV was increased from 384.73 to 1986.49 µg/g by 5.16-fold. After in vitro digestion, the contents of genistin, calycosin, formononetin, AG IV, Astragaloside II (AG II) and total flavonoids in fermented Radix Astragali (FRA) of enteric phase II (ENTII) were 34.52 µg/g, 207.32 µg/g, 56.76 µg/g, 2331.46 µg/g, 788.31 µg/g, 3.37 mg/g, which were 2.08-fold, 2.51-fold, 1.05-fold, 8.62-fold, 3.22-fold and 1.50-fold higher than those of control, respectively. The Scanning electron microscopy (SEM) of FRA showed rough surface and porous structure. The DPPH and ABTS radical scavenging rate of FRA were higher than those of control. These results showed that the Poria cocos solid fermentation could increase the content of the AG IV in Radix Astragali and improve the bioaccessibility and antioxidant activity of Radix Astragali, which is providing new ideas for future development and utilization of Radix Astragali.

The Analytical Strategy of "Ion Induction and Deduction Based on Net-Hubs" for the Comprehensive Characterization of Naringenin Metabolites In Vivo and In Vitro Using a UHPLC-Q-Exactive Orbitrap Mass Spectrometer.

Naringenin (5,7,4'-trihydroxyflavanone), belonging to the flavanone subclass, is associated with beneficial effects such as anti-oxidation, anticancer, anti-inflammatory, and anti-diabetic effects. Drug metabolism plays an essential role in drug discovery and clinical safety. However, due to the interference of numerous endogenous substances in metabolic samples, the identification and efficient characterization of drug metabolites are difficult. Here, ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry was used to obtain mass spectral information of plasma (processed by three methods), urine, feces, liver tissue, and liver microsome samples. Moreover, a novel analytical strategy named "ion induction and deduction" was proposed to systematically screen and identify naringenin metabolites in vivo and in vitro. The analysis strategy was accomplished by the establishment of multiple "net-hubs" and the induction and deduction of fragmentation behavior. Finally, 78 naringenin metabolites were detected and identified from samples of rat plasma, urine, feces, liver tissue, and liver microsomes, of which 67 were detected in vivo and 13 were detected in vitro. Naringenin primarily underwent glucuronidation, sulfation, oxidation, methylation, ring fission, and conversion into phenolic acid and their composite reactions. The current study provides significant help in extracting target information from complex samples and sets the foundation for other pharmacology and toxicology research.

Long-term PM2.5 exposure and various health outcomes: An umbrella review of systematic reviews and meta-analyses of observational studies.

Adverse effects from exposure to particulate matter <2.5 µm in diameter (PM2.5) on health-related outcomes have been found in a range of experimental and epidemiological studies. This study aimed to assess the significance, validity, and reliability of the relationship between long-term PM2.5 exposure and various health outcomes. The Embase, PubMed, Web of Science, CNKI, WANFANG, VIP, and SinoMed databases and reference lists of the retrieved review articles were searched to obtain meta-analysis and systematic reviews focusing on PM2.5-related outcomes as of August 31, 2021. Random-/fixed-effects models were applied to estimate summary effect size and 95% confidence intervals (CIs). The quality of included meta-analyses was evaluated based on the AMSTAR 2 tool. Small-study effect and excess significance bias studies were conducted to further assess the associations. Registered PROSPERO number: CRD42020200606. This included 24 articles involving 71 associations between PM2.5 exposure and the health outcomes. The evidence for the positive association of 10 µg/m3 increments of long-term exposure to PM2.5 and stroke incidence in Europe was convincing (effect size = 1.07, 95% CI: 1.05-1.10). There was evidence that was highly suggestive of a positive association between 10 µg/m3 increments of long-term exposure to PM2.5 and the following health-related outcomes: mortality of lung cancer (effect size = 1.11, 95% CI: 1.08-1.13) and Alzheimer's disease (effect size = 4.79, 95% CI: 2.79-8.21). There was highly suggestive evidence that chronic obstructive pulmonary disease risk is positively associated with higher long-term PM2.5 exposure versus lower long-term PM2.5 exposure (effect size = 2.32, 95% CI: 1.88-2.86). In conclusion, the positive association of long-term exposure to PM2.5 and stroke incidence in Europe was convincing. Given the validity of numerous associations of long-term exposure to PM2.5 and health-related outcomes is subject to biases, more robust evidence is urgently needed.

HuaChanSu suppresses tumor growth and interferes with glucose metabolism in hepatocellular carcinoma cells by restraining Hexokinase-2.

Hepatocellular carcinoma (HCC) has become the sixth highly diagnosed cancer and the fourth main reason of cancer deaths worldwide. HuaChanSu, an extract from dried toad skin, exhibits good anticancer effects and has been widely used in the treatment of liver cancer. The reprogramming of glucose metabolism is one remarkable feature of hepatocellular carcinoma, and the effects of HuaChanSu on the abnormal glucose metabolism of cancer cells have not been elucidated. In our study, we investigate the effects of HuaChanSu on glucose metabolism of hepatocellular carcinoma cells and tumor growth in vivo. The results show that HuaChanSu inhibits the tumor growth of hepatoma H22-bearing mice and prolongs the survival time of tumor-bearing mice, additionally, HuaChanSu has no obvious adverse effects in these mice. In vitro, HuaChanSu restrains the proliferation, induces apoptosis and cell cycle arrest of human hepatoma cells. HuaChanSu also promotes ROS production and causes mitochondrial damage. Furthermore, HuaChanSu inhibits glucose uptake and lactate release in human hepatoma cells. Mechanistically, we find that HuaChanSu downregulates Hexokinase-2 (HK2) expression, and using RNA interference, we confirm that HuaChanSu suppresses the growth of HepG2 cells by interfering with glucose metabolism through downregulation of Hexokinase-2. However, knockdown of Hexokinase-2 has no obvious effect on the proliferation of SK-HEP-1 cells, although glucose uptake and lactate release are reduced in siHK2-transfected SK-HEP-1 cells, subsequently, we illustrate that two human hepatoma cell lines exhibit glucose metabolism heterogeneity, which causes the different cell proliferation responses to the inhibition of Hexokinase-2. Taken together, our study indicates that HuaChanSu could inhibit tumor growth and interfere with glucose metabolism via suppression of Hexokinase-2, and these findings provide a new insight into the anti-hepatoma mechanisms of HuaChanSu and lay a theoretical foundation for the further clinical application of HuaChanSu.

Dietary Inflammatory Index and Risk of Asthenozoospermia: A Hospital-Based Case-Controlled Study in China.

Background: Evidence of associations between a pro-inflammatory diet and asthenozoospermia risk is limited. We therefore performed a case-controlled study to investigate associations between pro-inflammatory diet using dietary inflammatory index (DII) scores and asthenozoospermia risk in China. Methods: Our hospital-based case-controlled study comprised 549 incident asthenozoospermia men and 581 healthy controls. All were interviewed at the infertility clinic in Shengjing Hospital of China Medical University from June 2020 to December 2020. DII scores were calculated based on dietary intake which were assessed using a validated food frequency questionnaire. Semen parameters were analyzed according to World Health Organization guidelines. An unconditional logistic regression model was used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for asthenozoospermia risk. The lowest tertile served as the reference category for regression analyses. Results: After adjustment for age in the primary multivariable model, we failed to determine a significant negative association between DII and asthenozoospermia risk (for the highest tertile of DII scores compared to the lowest tertile) (OR = 0.77, 95% CI: 0.57-1.03). Similarly, non-significant associations were also identified in the multivariable model after adjusting for more potential confounders (OR = 0.86; 95% CI: 0.58-1.27). Additionally, in subgroup analyses stratified by age, body mass index, and smoking status, non-significant results were consistent with the main findings. Conclusions: To our knowledge, this is the first study exploring this particular topic. Our research does not support an association between DII scores and asthenozoospermia risk. Further prospective studies with more DII relevant foods and nutrients are warranted to confirm our findings.

Post-Diagnostic Beta Blocker Use and Prognosis of Ovarian Cancer: A Systematic Review and Meta-Analysis of 11 Cohort Studies With 20,274 Patients.

OBJECTIVES: Previous experimental studies have indicated that exposure to beta blocker provides protective effects against ovarian cancer (OC). However, findings from epidemiologic studies have still been controversial. Therefore, we carried out a meta-analysis to update and quantify the correlation between post-diagnostic beta blocker usage and OC prognosis. METHODS: The meta-analysis had been registered at PROSPEPO. The number of registration is CRD42020188806. A comprehensive search of available literatures in English prior to April 16, 2020, was conducted in PubMed, EMBASE, and the Web of Science databases. Random-effects models were used to calculate overall hazard ratios (HRs) and 95% confidence intervals (CIs). Publication bias assessments, and subgroup, sensitivity, and meta-regression analyses were also performed. RESULTS: Of the 637 initially identified articles, 11 retrospective cohort studies with 20,274 OC patients were included. The summary HRs did not reveal any statistically significant associations between post-diagnostic beta blocker use and OC prognosis characteristics, such as total mortality (HR = 1.08, 95% CI = 0.92-1.27, I2 = 76.5%, n = 9), cancer-specific mortality (HR = 1.22, 95% CI = 0.89-1.67, I2 = 88.1%, n=3), and progression-free survival (HR = 0.88, 95% CI = 0.75-1.05, I2 = 0, n = 4). No evidence of publication bias was observed in current analysis. In our subgroup analyses, the majority of results were consistent with the main findings. However, several positive correlations were detected in studies with ≥800 cases (HR = 1.20, 95% CI = 1.05-1.37), no immortal time bias (HR = 1.28, 95% CI = 1.10-1.49), and adjustment for comorbidity (HR = 1.20, 95% CI = 1.05-1.37). In the meta-regression analysis, no evidence of heterogeneity was detected in the subgroups according to study characteristics and confounding factors. CONCLUSIONS: Post-diagnostic beta blocker use has no statistical correlation with OC prognosis. More prospective cohort studies are necessary to further verify our results. SYSTEMATIC REVIEW REGISTRATION: Identifier (CRD42020188806).

Dietary Inflammatory Index and Health Outcomes: An Umbrella Review of Systematic Review and Meta-Analyses of Observational Studies.

Background and Aims: The dietary inflammatory index (DII) is associated with non-communicable disease. We conducted an umbrella review to systematically evaluate meta-analyses of observational studies on DII and diverse health outcomes. Methods: We comprehensively searched the PubMed, Web of Science, and Embase databases to identify related systematic reviews and meta-analyses of observational studies. Those investigating the association between DII and a wide range of health outcomes in humans were eligible for inclusion. For each meta-analysis, we estimated the summary effect size by using fixed and random effects models, the 95% confidence interval, and the 95% prediction interval. We assessed heterogeneity, evidence of small-study effects, and excess significance bias. Results: The umbrella review identified 35 meta-analyses assessing associations between DII and various health outcomes: cancer (n = 24), mortality (n = 4), metabolic (n = 4), and other (n = 3). The methodological quality was high or moderate. Of the 35 meta-analyses, we observed highly suggestive evidence for harmful associations between digestive tract cancer, colorectal cancer, overall cancer, pharyngeal cancer, UADT cancer, and CVD mortality. Moreover, 11 harmful associations showed suggestive evidence: hormone-dependent cancer, rectal cancer, colon cancer, breast and prostate cancer, gynecological cancer, breast cancer, ovarian cancer, colorectal cancer, prostate cancer, all-cause mortality, and depression. Conclusion: DII is likely to be associated with harmful effects in multiple health outcomes. Robust randomized controlled trials are warranted to understand whether the observed results are causal. Systematic Review Registration: CRD42021218361.

Risk Factors and a New Prediction Model for Pancreatic Fistula After Pancreaticoduodenectomy.

AIM: In order to find the risk factors of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) according to the latest definition and grading system of International Study Group of Pancreatic Surgery (ISGPS) (version 2016) and propose a nomogram for predicting POPF. METHODS: We conducted a retrospective analysis of 232 successive cases of PD performed at our hospital by the same operator from August 2012 to June 2020. POPF was diagnosed in accordance with the latest definition of pancreatic fistula from the ISGPS. The risk factors of POPF were analyzed by univariate and multivariate logistic regression analysis. A nomogram model to predict the risk of POPF was constructed based on significant factors. RESULTS: There were 18 cases of POPF, accounting for 7.8% of the total. Among them, 17 cases were classified into ISGPF grade B and 1 case was classified into ISGPF grade C. In addition, 35 cases were classified into biochemical leak. Univariate and multivariate analysis showed that hypertension, non-diabetes, no history of abdominal surgery, antecolic gastrojejunostomy and soft pancreas were independent risk factors of POPF. Based on significant factors, a nomogram is plotted to predict the risk of POPF. The C-index of this nomogram to assess prediction accuracy was 0.916 (P < 0.001) indicating good prediction performance. CONCLUSION: Hypertension, non-diabetes, no history of abdominal surgery, antecolic gastrojejunostomy and soft pancreas were independent risk factors of POPF. Meanwhile, a nomogram for predicting POPF with good test performance and discriminatory capacity was constituted.

Immunogenomic Profiling Demonstrate AC003092.1 as an Immune-Related eRNA in Glioblastoma Multiforme.

Enhancer RNAs, a type of long non-coding RNAs (lncRNAs), play a critical role in the occurrence and development of glioma. RNA-seq data from 161 glioblastoma multiforme (GBM) samples were acquired from The Cancer Genome Atlas database. Then, 70 eRNAs were identified as prognosis-related genes, which had significant relations with overall survival (log-rank test, p < 0.05). AC003092.1 was demonstrated as an immune-related eRNA by functional enrichment analysis. We divided samples into two groups based on AC003092.1 expression: AC003092.1 High (AC003092.1_H) and AC003092.1 Low (AC003092.1_L) and systematically analyzed the influence of AC003092.1 on the immune microenvironment by single-sample gene-set enrichment analysis and CIBERSORTx. We quantified AC003092.1 and TFPI2 levels in 11 high-grade gliomas, 5 low-grade gliomas, and 7 GBM cell lines. Our study indicates that AC003092.1 is related to glioma-immunosuppressive microenvironment, and these results offer innovative sights into GBM immune therapy.

Maternal exposure to ambient levels of sulfur dioxide and risk of neural tube defects in 14 cities in Liaoning province, China: a population-based case-control study.

Epidemiological studies on the association of sulfur dioxide (SO2) with neural tube defects (NTDs) are lacking. The purpose of this study was to assess the aforementioned association through a population-based case-control study. This study involved 1457 NTDs cases and 7950 randomly selected healthy infants born in 14 cities in Liaoning province between 2010 and 2015. Ambient SO2 levels were acquired from 75 monitoring stations. The exposure assessment was based on the mean concentration of all stations in mother's residential city. We used logistic regression models to assess the associations. In multivariable models adjusted for the confounding variables selected based on the 10 percent change-in-estimate method, we found that maternal SO2 exposure was positively associated with an increased risk of NTDs during the first month after conception (per 10 µg/m3 increase: adjusted odds ratio [aOR] = 1.02, 95% confidence interval [CI]: 1.00-1.04; highest versus lowest quartile: aOR = 2.55, 95% CI: 1.97-3.31) and the second month after conception (per 10 µg/m3 increase: aOR = 1.02, 95% CI: 1.00-1.04; highest versus lowest quartile: aOR=2.31, 95% CI: 1.77-3.00). For other exposure windows, positive associations also emerged in high- versus low-exposure analyses, except for the third month before conception; however, we could not further confirm significant findings from the continuous exposure analyses. Our study provides a new evidence that SO2 exposure may increase the risk of NTDs.

[Effects of CeO2 nanoparticles on the viabilities of neural PC12 and SH-SY5Y cells].

OBJECTIVE: To investigate the effects of cerium oxide (CeO2) nanoparticles on the viabilities of nerve cells PC12 and SH-SY5Y. METHODS: CeO2 nanoparticles were synthesized, structures were characterized and properties were evaluated. PC12 cells and SH-SY5Y cells were treated with CeO2 nanoparticles at different concentrations (1, 2.5, 5, 10, 25, 50, 75, 100, 150 µg/ml) for 24 h and the cell viability was measured by MTT assay. Then PC12 cells and SH-SY5Y cells were co-treated with CeO2 and active oxygen scavenger NAC and the cells were stained with DCFH-DA probe for ROS. The number of cells and the fluorescence intensity were observed under a fluorescent inverted microscope. Differences were assessed by one-way ANOVA. RESULTS: After treatment with CeO2 nanoparticles, the viabilities of both PC12 cells (P＜0.01) and SH-SY5Y cells (P＜0.01) were decreased comparing with the control group. After staining with DCFH-DA probe, the fluorescence intensity of the nerve cells was enhanced depending on the concentration of CeO2 nanoparticles suggesting that CeO2 induced the generation of reactive oxygen species (ROS). The fluorescence intensity of PC12 cells was decreased after CeO2 nanoparticles (100 µg/ml) co-treatment with active oxygen scavenger NAC. Compared with CeO2 nanoparticles alone at 25 µg/ml (P＜0.01), 50 µg/ml (P＜0.01), 75 µg/ml (P＜0.01), 100 µg/ml (P＜0.01), the cell viability was significantly increased after co-treatment with NAC. CONCLUSION: CeO2 nanoparticles has a negative effect on the viabilities of nerve cells PC12 and SH-SY5Y, and the effect might be depend on ROS.

Pancreaticopleural fistula in children with chronic pancreatitis: a case report and literature review.

BACKGROUND: Pancreaticopleural fistula (PPF) is a very rare and critical complication of pancreatitis in children. The majority of publications relevant to PPF are case reports. No pooled analyses of PPF cases are available. Little is known about the pathogenesis and optimal therapeutic schedule. The purpose of this study was to identify the pathogenesis and optimal therapeutic schedule of PPF in children. CASE PRESENTATION: The patient was a 13-year-old girl who suffered from intermittent chest tightness and dyspnea for more than 3 months; she was found to have chronic pancreatitis complicated by PPF. The genetic screening revealed SPINK1 mutation. She was treated with endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic retrograde pancreatic drainage (ERPD); her symptoms improved dramatically after the procedures. CONCLUSIONS: PPF is a rare pancreatic complication in children and causes significant pulmonary symptoms that can be misdiagnosed frequently. PPF in children is mainly associated with chronic pancreatitis (CP); therefore, we highlight the importance of genetic testing. Endoscopic treatment is recommended when conservative treatment is ineffective.