Nomograms for Predicting Survival Outcomes in Patients with Neuroendocrine Neoplasms of the Gallbladder Undergoing Primary Tumor Resection: A Population-Based Study.

BACKGROUND: Neuroendocrine neoplasms of the gallbladder (GB-NENs) are a rare group of histologically heterogeneous tumors, and surgical resection of the primary tumor is the mainstream treatment at the moment. The current study aimed to establish and validate novel nomograms for patients with GB-NENs undergoing primary tumor resection to predict the 6-, 12-, and 18-month overall survival (OS) and cancer-specific survival (CSS). METHODS: Clinicopathological information of patients with GB-NENs undergoing primary tumor resection between 2004 and 2018 was derived from the Surveillance, Epidemiology, and End Results (SEER) database. Candidate prognostic factors were selected by Cox regression analyses, and the nomograms were constructed. Finally, concordance index (C-index), calibration plot, area under the curve from the receiver operating characteristic curve (AUC), and decision curve analysis (DCA) were utilized to assess the effective performance of the nomograms. RESULTS: A total of 221 patients with GB-NENs undergoing resection were enrolled in this retrospective study. Using the Cox regression analyses, age, pathological classification, tumor size, and SEER stage were identified as the independent prognostic factors of patients with GB-NENs undergoing resection, and nomograms were constructed. The C-indexes of OS and CSS in training dataset were 0.802 (95% CI: 0.757-0.848) and 0.846 (95% CI: 0.798-0.895), while those of internal validation dataset were 0.862 (95% CI: 0.802-0.922) and 0.879 (95% CI: 0.824-0.934), respectively. CONCLUSIONS: Taken together, the nomograms are accurate enough to predict the prognostic factors of GB-NEN patients undergoing resection, allowing for treatment decision-making and clinical monitoring for future clinical work.

Selection of optimal models for predicting growth stress in Artemisia desertorum by comparison of linear regression and multiple neural networks: Take the construction of a green mine in the Bayan Obo mine as an example.

In recent years, more and more countries are focusing on the control of mining sites and the surrounding ecological environment, and the new environmental concept of green mines has been proposed. By investigating the ecological background of a mine site, pollution and ecological imbalances in the mine can be predicted, managed or transformed. This study investigated the effects of rare earth elements on plant growth in the Baotou Bayan Obo Rare Earth Mine and evaluated soil contamination and subsequent remediation through the measured plant height. Using linear regression, BP(Back Propagation) neural networks, GA-BP(Genetic Algorithm- Back Propagation) neural networks, ELM(Extreme Learning Machine) and GA-ELM(Genetic Algorithm- Extreme Learning Machine) model prediction instruments, the different rare earth solution concentrations were set as input values and the heights of Artemisia desertorum, which as the model plant, were set as output values in the prediction. The results showed that the linear regression predicted the standard error of single La(III), Ce(III) solution and compound La(III) + Ce(III) solution for Artemisia desertorum growth stress was on the high side, 7.02%- 8.92%; the efficiency range of each group of models under BP neural network, GA-BP neural network and ELM neural network were 1.15%- 2.53%, 0.85%- 1.28%, 1.76%- 3.53%; while the efficiency range under GA-ELM neural network was 0.59%- 0.68%, with average error values and predicted values close to the true values. Among them, the MAPE of GA-ELM neural network are significantly lower than other models, and the error decreases with increasing concentration of the compound solution. So GA-ELM neural network can be used as an efficient, fast and reasonable optimal model for predicting the growth stress of Artemisia desertorum in Bayan Obo mining area. The experimental results can provide a theoretical basis for assessing the risk of soil rare earth contamination in the area, evaluating the expectation of later remediation, and provide a degree of new ideas for the construction of green mines.

Low-dose lipopolysaccharide protects nerve cells against spinal cord injury via regulating the PI3K-AKT-Nrf2 signaling pathway.

This study explored the molecular mechanism behind the protective effects from low-dose lipopolysaccharide (LPS) on an in-vitro model of spinal cord injury (SCI). For this, PC12 cells were treated with different concentrations of LPS and the cell counting kit-8 assay was used to measure the toxicity of LPS to the cells. Next, we used immunofluorescence to measure nuclear translocation of Nrf2 in PC12 cells. PC12 cells were then treated with IGF-1 (PI3K agonist) and LY294002 (PI3K inhibitor). An in-vitro model of SCI was then established via oxygen-glucose deprivation/reoxygenation. Rates of apoptosis were measured using flow cytometry and the TUNEL assay. Low-dose LPS increased the expression levels of Nrf2, p-PI3K/PI3K, and p-AKT/AKT, and facilitated nuclear translocation of Nrf2. The activation of PI3K-AKT signaling by IGF-1 significantly increased the expression of Nrf2, whereas inhibition of PI3K-AKT signaling significantly decreased the expression of Nrf2. Low-dose LPS reduced the apoptotic ratio of PC12 cells, decreased the expression levels of caspase 3 and caspase 9, and increased the expression levels of HO-1, NQO1, and γ-GCS. Low-dose LPS also reduced the rate of apoptosis and oxidative stress by activating the PI3K-AKT-Nrf2 signaling pathway. Collectively, the results indicate that PI3K-AKT-Nrf2 signaling participates in the protective effects from low-dose LPS in an in-vitro PC12 cell model of SCI.

Application value analysis of magnetic resonance imaging and computed tomography in the diagnosis of intracranial infection after craniocerebral surgery.

BACKGROUND: Intracranial infection is a common clinical disease. Computed tomography (CT) and magnetic resonance imaging (MRI) have certain sensitivity and have good diagnostic efficacy. AIM: To study the application value of MRI and CT in the diagnosis of intracranial infection after craniocerebral surgery. METHODS: We selected 82 patients who underwent craniocerebral surgery (including 40 patients with intracranial infection and 42 patients without infection) during the period from April 2016 to June 2019 in our hospital. All 82 patients received CT and MRI examinations, and their clinical data were reviewed. A retrospective analysis was performed, and the coincidence rate of positive diagnosis and the overall diagnosis coincidence rate of different pathogenic infection types were measured with the two examination methods. The diagnostic sensitivity and specificity as well as the positive and negative predictive values of the two examination methods were compared. RESULTS: For all types of pathogenic infections (Staphylococcus aureus, Staphylococcus hemolyticus, Staphylococcus epidermidis, and others), MRI scans had higher positive diagnostic coincidence rates than CT scans; the overall diagnostic coincidence rate, sensitivity, specificity, positive predictive value, and negative predictive values were significantly higher with MRI examinations than with CT examinations, and the differences were statistically significant (P < 0.05). CONCLUSION: MRI examination can accurately diagnose intracranial infection after clinical craniocerebral surgery. Compared with CT, MRI had higher diagnostic efficiency. The diagnostic sensitivity and specificity, the diagnostic coincidence rate, and the positive and negative predictive values were significantly higher with MRI than with conventional CT, which can be actively promoted.

Baguan Therapy Is an Alternative in Treating Ankylosing Spondylitis: A Systematic Review Based on Existing Randomized Controlled Trials.

BACKGROUND: The aim of this systematic review was to evaluate the evidence available on the effects of Baguan therapy for ankylosing spondylitis (AS) patients. MATERIALS AND METHODS: The following databases were searched from their inception to August 2018: PubMed, Web of Science, AMED, Cochrane Library, Google, EMBASE, the China National Knowledge Infrastructure databases, Wanfang Data, CiNii, KoreaMed, and the Iranian Registry of Clinical Trials. Randomized controlled trials (RCTs), which assessed the effects of Baguan therapy for AS, were included in our review. The methodological quality of eligible studies was assessed by the Cochrane Collaboration's tool. The RevMan 5.3 software was used for quantitative analysis of RCTs. Heterogeneity was assessed using I2 statistics. RESULTS: Four studies were included in our review. The aggregated results indicated that Baguan therapy improved the treatment effect (risk ratio 1.21, 95% CI 1.10-1.34, p < 0.01) as well as physical function (Bath Ankylosing Spondylitis Functional Index) (mean difference -1.56, 95% CI -2.01 to -1.12, p < 0.01) and reduced disease activity (Bath Ankylosing Spondylitis Disease Activity Index) (mean difference -0.71, 95% CI -1.09 to -0.33, p < 0.01) in patients with AS. CONCLUSION: Due to the low quality of included trials, it is difficulty to draw the firm conclusion that Baguan therapy may have beneficial effects on AS.

Hydrothermal Synthesis of Co-Doped NiSe2 Nanowire for High-Performance Asymmetric Supercapacitors.

Co@NiSe2 electrode materials were synthesized via a simple hydrothermal method by using nickel foam in situ as the backbone and subsequently characterized by scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, and a specific surface area analyzer. Results show that the Co@NiSe2 electrode exhibits a nanowire structure and grows uniformly on the nickel foam base. These features make the electrode show a relatively high specific surface area and electrical conductivity, and thus exhibit excellent electrochemical performance. The obtained electrode has a high specific capacitance of 3167.6 F·g-1 at a current density of 1 A·g-1. To enlarge the potential window and increase the energy density, an asymmetric supercapacitor was assembled by using a Co@NiSe2 electrode and activated carbon acting as positive and negative electrodes, respectively. The prepared asymmetrical supercapacitor functions stably under the potential window of 0⁻1.6 V. The asymmetric supercapacitor can deliver a high energy density of 50.0 Wh·kg-1 at a power density of 779.0 W·kg-1. Moreover, the prepared asymmetric supercapacitor exhibits a good rate performance and cycle stability.

A MoO2 sheet as a promising electrode material: ultrafast Li-diffusion and astonishing Li-storage capacity.

The potential of MoO2 crystal as an electrode material is reported, and nanostructural MoO2 systems, including nanoparticles, nanospheres, nanobelts and nanowires, were synthesized and proved to be advanced electrode materials. A two-dimensional (2D) geometric structure represents an extreme of surface-to-volume ratio, and thus is more suitable as an electrode material in general. Stimulated by the recent fabrication of 2D MoO2, we adopted an ab initio molecular dynamics simulation and density functional theory calculation to study the stability and electrochemical properties of a MoO2 sheet. Identified by a phonon dispersion curve and potential energy curve calculations, the MoO2 sheet proved to be dynamically and thermally stable. After lithiation, similar to most promising 2D structures, we found that a Li atom can strongly adsorb on a MoO2 sheet, and the lithiated MoO2 sheet presented excellent metallic properties. Note that, compared with most promising 2D structures, we unexpectedly revealed that the diffusion barrier of the Li atom on the MoO2 sheet was much lower and the storage capacity of the MoO2 sheet was much larger. The calculated energy barrier for the diffusion of Li on the MoO2 sheet was only 75 meV, and, due to multilayer adsorption, the theoretical capacity of the MoO2 sheet can reach up to 2513 mA h g-1. Benefiting from general properties, such as strong Li-binding and excellent conductivity, and unique phenomena, such as ultrafast diffusion capacity and astonishing storage capacity, we highlight a new promising electrode material for the Li-ion battery.

Value of Ultrasonographic Features for Assessing Malignant Potential of Complex Cystic Breast Lesions.

OBJECTIVES: To assess the value of ultrasonography (US) features for determining the malignant potential of complex cystic lesions. METHODS: Seventy-nine complex cystic lesions were reviewed retrospectively. They were classified into four types according to US features in type I, the masses have a thick outer wall, thick internal septa, or both; in type II, the masses are an intracystic type with one or more discrete solid mural lesions within a cyst; in type III, the masses contain mixed cystic and solid components and are at least 50% cystic portion in a mass; in type IV, there are predominantly (at least 50%) solid masses with eccentric or central cystic foci. Positive predictive values were calculated for all types. RESULTS: The frequency of malignancy was higher among type III and IV lesions than among the other two types. Lesions with a diameter greater than or equal to 20 mm, margins not circumscribed, resistance index greater than or equal to 0.7, and axillary abnormal nodes had a high probability of malignancy. CONCLUSIONS: US is an important adjunct to evaluate the malignant potential of complex cystic lesions.

Long-chain non-coding RNA DAPK1 targeting miR-182 regulates pancreatic cancer invasion and metastasis through ROCK-1/rhoa signaling pathway.

OBJECTIVE: To investigate the expression of long-chain non-coding RNAs DAPK1 and miR-182 in pancreatic cancer tissues and the role of DAPK1 and miR-182 in pancreatic cancer cell invasion and migration and its mechanism. METHODS: The expression of DAPK1 and miR-182 in different pancreatic cancer and adjacent tissues and different pancreatic cancer cells were detected by qPCR. Transwell invasion assay was used to detect the invasion ability of pancreatic cancer cells after DAPK1 expression. The changes of the migration ability of pancreatic cancer cells after DAPK1 expression were detected by scratch test. Double luciferase reporter gene was used to detect the interaction between DAPK1 and miR-182. Transwell invasion assay showed that miR-182 overexpression of DAPK1 could restore the invasive ability of pancreatic cancer cells. Western blot was used to detect the expression of ROCK-1/RhoA pathway protein after overexpression of miR-182 in DAPK1 cells. Phalloidin was used to label the cytoskeleton. The effect of miR-182 overexpression of DAPK1 on tumor size and volume of pancreatic cancer was detected by subcutaneous tumor formation in nude mice. RESULTS: The expression of DAPK1 was significantly decreased in pancreatic cancer tissues compared with adjacent tissues, and the expression of DAPK1 decreased gradually and the expression of miR-182 was opposite with the progression of tumor. DAPK1 was associated with pathological stage of pancreatic cancer and lymph node metastasis, while miR-182 was positively correlated. The expression level of DAPK1 in pancreatic cancer cell HS766T was the lowest. Overexpression of DAPK1 could inhibit the invasion and migration of pancreatic cancer cells. DAPK1 could bind specifically to 3'UTR of miR-182. Overexpression of miR-182 could restore the invasion and migration of pancreatic cancer cells after overexpression of DAPK1. The expression of ROCK-1/RhoA pathway protein was down-regulated by miR-182 after expression of DAPK1, and the expression of ROCK-1/RhoA pathway protein was restored. The expression of F-actin in LV5-DAPK1 group was significantly decreased, the formation of cell membrane wrinkles was significantly reduced, and the formation of pseudopodia was significantly reduced compared with LV5-DAPK1 + miR-182-mimic group. The tumor volume and weight of tumor-bearing mice in LV5-DAPK1 + miR-182-mimic group were significantly increased compared with LV5-DAPK1 group. CONCLUSION: DAPK1 plays an important role in the development and progression of pancreatic cancer. DAPK1 can regulate the invasion and migration of pancreatic cancer cells through the regulation of miR-82 through ROCK-1/RhoA signaling pathway.

Low-level sodium arsenite induces apoptosis through inhibiting TrxR activity in pancreatic ß-cells.

In our previous study, we reported that sodium arsenite induced ROS-dependent apoptosis through lysosomal-mitochondrial pathway in pancreatic ß-cells. Since the thioredoxin (Trx) system is the key antioxidant factor in mammalian cells, we investigate whether the inhibition of Trx system contributes to sodium arsenite-induced apoptosis in this study. After treatment with low-level (0.25-1µM) sodium arsenite for 96h, the thioredoxin reductase (TrxR) activity was decreased significantly in pancreatic INS-1 cells. Following with the inactivation of TrxR, ASK1 was released from combining with Trx, which was evidenced by increased levels of ASK1 in sodium arsenite-treated INS-1 cells. Subsequently, activated ASK1 accelerated the expression of proapoptotic protein Bax and reduced the expression of anti-apoptic protein Bcl-2. Finally, low-level sodium arsenite induced apoptosis via caspase-3 in INS-1 cells. Knockdown of ASK1 alleviated sodium arsenite-induced apoptosis. In summary, the precise molecular mechanisms through which arsenic is related to diabetes have not been completely elucidated, inactivation of Trx system might provide insights into the underlying mechanisms at the environmental exposure levels.

Effect of mesenchymal stem cells transplantation combining with hyperbaric oxygen therapy on rehabilitation of rat spinal cord injury.

OBJECTIVE: To investigate the effect of BMSCs transplantation plus hyperbaric oxygen (HBO) on repair of rat SCI. METHODS: Seventy five male rats were divided randomly into five groups: sham, vehicle, BMSCs transplantation group, combination group, 15 rats in each group. Every week after the SCI onset, all animals were evaluated for behavior outcome by Basso-Beattle-Bresnahan (BBB) score and inclined plane test. Axon recovery was examined with focal spinal cord tissue by electron microscope at 6 weeks after the SCI onset. HE staining and BrdU staining were performed to examine the BMSCs and lesion post injury. Somatosensory evoked potential (SEP) testing was performed to detect the recovery of neural conduction. RESULTS: Results from the behavior tests from combination group were significant higher than rats which received only transplantation or HBO treatment. Results from histopathology showed favorable recovery from combination group than other treatment groups. The number of BrdU(+) in combination group were measureable more than transplantation group (P < 0.05). The greatest decrease in TNF-α, IL-1ß, IL-6, IFN-α determined by Elisa assay in combination group were evident too. CONCLUSIONS: BMSCs transplantation can promote the functional recovery of rat hind limbs after SCI, and its combination with HBO has a synergistic effect.

The effects of hyperbaric oxygen on macrophage polarization after rat spinal cord injury.

The immunoreactive responses are a two-edged sword after spinal cord injury (SCI). Macrophages are the predominant inflammatory cells responsible for this response. However, the mechanism underlying the effects of HBOT on the immunomodulation following SCI is unclear now. The present study was performed to examine the effects of hyperbaric oxygen therapy (HBOT) on macrophage polarization after the rat compressive injury of the spinal cord. HBOT was associated with significant increases in IL-4 and IL-13 levels, and reductions in TNF-α and IFN-É£ levels. This was associated simultaneously with the levels of alternatively activated macrophages (M2 phenotype: arginase-1- or CD206-positive), and decreased levels of classically activated macrophages (M1 phenotype: iNOS- or CD16/32-positive). These changes were associated with functional recovery in the HBOT-transplanted group, which correlated with preserved axons and increased myelin sparing. Our results suggested that HBOT after SCI modified the inflammatory environment by shifting the macrophage phenotype from M1 to M2, which may further promote the axonal extension and functional recovery.

Citreoviridin induces ROS-dependent autophagic cell death in human liver HepG2 cells.

Citreoviridin (CIT) is one of toxic mycotoxins derived from fungal species in moldy cereals. Whether CIT exerts hepatotoxicity and the precise molecular mechanisms of CIT hepatotoxicity are not completely elucidated. In this study, the inhibitor of autophagosome formation, 3-methyladenine, protected the cells against CIT cytotoxicity, and the autophagy stimulator rapamycin further decreased the cell viability of CIT-treated HepG2 cells. Knockdown of Atg5 with Atg5 siRNA alleviated CIT-induced cell death. These finding suggested the hypothesis that autophagic cell death contributed to CIT-induced cytotoxicity in HepG2 cells. CIT increased the autophagosome number in HepG2 cells observed under a transmission electron microscope, and this effect was confirmed by the elevated LC3-II levels detected through Western blot. Reduction of P62 protein levels and the result of LC3 turnover assay indicated that the accumulation of autophagosomes in the CIT-treated HepG2 cells was due to increased formation rather than impaired degradation. The pretreatment of HepG2 cells with the ROS inhibitor NAC reduced autophagosome formation and reversed the CIT cytotoxicity, indicating that CIT-induced autophagic cell death was ROS-dependent. In summary, ROS-dependent autophagic cell death of HpeG2 cells described in this study may help to elucidate the underlying mechanism of CIT cytotoxicity.

The role of oxidative stress in citreoviridin-induced DNA damage in human liver-derived HepG2 cells.

We hypothesize that citreoviridin (CIT) induces DNA damage in human liver-derived HepG2 cells through an oxidative stress mechanism and that N-acetyl-l-cysteine (NAC) protects against CIT-induced DNA damage in HepG2 cells. CIT-induced DNA damage in HepG2 cells was evaluated by alkaline single-cell gel electrophoresis assay. To elucidate the genotoxicity mechanisms, the level of oxidative DNA damage was tested by immunoperoxidase staining for 8-hydroxydeoxyguanosine (8-OHdG); the intracellular generation of reactive oxygen species (ROS) and reduced glutathione (GSH) were examined; mitochondrial membrane potential and lysosomal membranes' permeability were detected; furthermore, protective effects of NAC on CIT-induced ROS formation and CIT-induced DNA damage were evaluated in HepG2 cells. A significant dose-dependent increment in DNA migration was observed at tested concentrations (2.50-10.00 µM) of CIT. The levels of ROS, 8-OHdG formation were increased by CIT, and significant depletion of GSH in HepG2 cells was induced by CIT. Destabilization of lysosome and mitochondria was also observed in cells treated with CIT. In addition, NAC significantly decreased CIT-induced ROS formation and CIT-induced DNA damage in HepG2 cells. The data indicate that CIT induces DNA damage in HepG2 cells, most likely through oxidative stress mechanisms; that NAC protects against DNA damage induced by CIT in HepG2 cells; and that depolarization of mitochondria and lysosomal protease leakage may play a role in CIT-induced DNA damage in HepG2 cells.

Seroepidemiology and genetic characterization of hepatitis E virus in western Yunnan Province.

OBJECTIVE: To investigate the seroepidemiology and genetic characterization of hepatitis E virus (HEV) in western Yunnan Province. METHODS: Questionnaire survey was conducted among 1638 residents in western Yunnan Province using stratified sampling method. Enzyme-linked immunosorbent assay was used to detect serum anti-HEV IgG and IgM. HEV RNA was extracted from patients with serum anti-HEV IgM positive. The open reading flame 2 (ORF2) of HEV that was amplified by nested RT-PCR was sequenced and compared with standard HEV genotypes 1-4. RESULTS: Serum anti-HEV positive was found in 13.92% (228/1638) residents. The HEV infection rate in males was significantly higher than that in females with a ratio of 1.47 (P<0.01). 20-30 and 30-40 years old young men showed the highest incidence, 20.57% and 20.78%, respectively. While 10-20 and 20-30 years old young women exhibited the highest infection rate, 11.85% and 15.60%, respectively. According to occupation, the highest HEV infection rate was observed in farmers (20.35%) and migrants (16.50%). We isolated 10 individual HEV isolates from 31 patients with serum anti-HEV IgM positive. Homology analysis and phylogenetic analysis indicated that these 10 HEV isolates belonged to HEV genotype 4 with the homology of 78.65%-94.71%. CONCLUSIONS: The HEV infection rate is high in western Yunnan Province. HEV genotype 4 is the leading cause of HEV infection and young farmers and migrants are the main infected population.

Knockdown of OCT4 suppresses the growth and invasion of pancreatic cancer cells through inhibition of the AKT pathway.

Octamer­binding transcription factor 4 (OCT4) is one of the factors associated with self­renewal and differentiation in cancer stem cells, and is crucial for the progression of various types of human malignancy. However, the expression and function of OCT4 in human pancreatic cancer has not been fully elucidated. The purpose of the present study was to investigate the function and molecular mechanisms of OCT4 in pancreatic cancer cells. The clinical significance of OCT4 expression was assessed by an immunohistochemical assay using a tissue microarray procedure in pancreatic cancer tissues and cells with different degrees of differentiation. A loss­of­function approach was used to examine the effects of a lentivirus­mediated OCT4 small hairpin RNA vector on biological behaviors, including cell proliferative activity and invasive potential. The results demonstrated that the expression levels of OCT4 protein in cancer tissues were significantly elevated compared with those in adjacent non­cancerous tissues (65.0 vs. 42.5%; P=0.005), which was correlated with tumor differentiation (P=0.008). The knockdown of OCT4 inhibited the proliferation and invasion of pancreatic cancer cells (Panc­1) expressing high levels of OCT4, accompanied with decreased expression of AKT, proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase­2 (MMP­2). In conclusion, the present study reveals that the increased expression of OCT4 is correlated with the differentiation of pancreatic cancer, while knockdown of OCT4 suppresses the growth and invasion of pancreatic cancer cells through inhibition of AKT pathway­mediated PCNA and MMP­2 expression, suggesting that OCT4 might serve as a potential therapeutic target for the treatment of pancreatic cancer.

Sodium arsenite induces ROS-dependent autophagic cell death in pancreatic ß-cells.

Inorganic arsenic is a worldwide environmental pollutant. Inorganic arsenic's positive relationship with the incidence of type 2 diabetes mellitus arouses concerns associated with its etiology in diabetes among the general human population. In this study, the inhibitor of autophagosome formation, 3-methyladenine, protected the cells against sodium arsenite cytotoxicity, and the autophagy stimulator rapamycin further decreased the cell viability of sodium arsenite-treated INS-1 cells. These finding suggested the hypothesis that autophagic cell death contributed to sodium arsenite-induced cytotoxicity in INS-1 cells. Sodium arsenite increased the autophagosome-positive puncta in INS-1 cells observed under a fluorescence microscope, and this effect was confirmed by the elevated LC3-II levels detected through Western blot. The LC3 turnover assay indicated that the accumulation of autophagosomes in the arsenite-treated INS-1 cells was due to increased formation rather than impaired degradation. The pretreatment of INS-1 cells with the ROS inhibitor NAC reduced autophagosome formation and reversed the sodium arsenite cytotoxicity, indicating that sodium arsenite-induced autophagic cell death was ROS-dependent. In summary, the precise molecular mechanisms through which arsenic is related to diabetes have not been completely elucidated, but the ROS-dependent autophagic cell death of pancreatic ß-cells described in this study may help to elucidate the underlying mechanism.

Perfluorooctane sulfonate blocked autophagy flux and induced lysosome membrane permeabilization in HepG2 cells.

Perfluorooctane sulfonate (PFOS) is an emerging persistent organic pollutant widely distributed in the environment, wildlife and human. In this study, as observed under the transmission electron microscope, PFOS increased autophagosome numbers in HepG2 cells, and it was confirmed by elevated LC3-II levels in Western blot analysis. PFOS increased P62 level and chloroquine failed to further increase the expression of LC3-II after PFOS treatment, indicating that the accumulation of autophagosome was due to impaired degradation rather than increased formation. With acridine orange staining, we found PFOS caused lysosomal membrane permeabilization (LMP). In this study, autophasome formation inhibitor 3-methyladenine protected cells against PFOS toxicity, autophagy stimulator rapamycin further decreased cell viability and increased LDH release, cathepsin inhibitor did not influence cell viability of PFOS-treated HepG2 cells significantly. These further supported the notion that autophagic cell death contributed to PFOS-induced hepatotoxicity. In summary, the data of the present study revealed that PFOS induced LMP and consequent blockage of autophagy flux, leading to an excessive accumulation of the autophagosomes and turning autophagy into a destructive process eventually. This finding will provide clues for effective prevention and treatment of PFOS-induced hepatic disease.

Urethral realignment for treating early urethral injury under the guidance of ureteroscope / 中国医师进修杂志

Objective To summarize the clinical experience of urethral realignment for treating early urethral injury under the guidance of ureteroscope,and evaluate its curative effect.Methods Twenty-nine male patients with urethral injury were selected,and 12 patients of posterior urethral injury,17 patients of former urethral injury.All the patients were treated with urethral realignment under the guidance of ureteroscope,postoperative indwelling catheter 3-8 weeks,every 7-16 days changed diameter increase 2 F the catheter 1 time.Results The 29 patients with urethral injury were a indwelling catheter success,all patients were no incontinence after operation 3 months.In the 29 patients,27 patients were urination unobstructed after catheter removal,2 patients were appeared urine line slim after 2 weeks,the 2 patients were normal urination after short urethral expansion.Conclusions The urethral realignment for treating early urethral injury under the guidance of ureteroscope has simple,lower complication,rapid recovery,better effect.The continuous flexible progressive urethral expansion and the strict nursing,which can effectively reduce the occurrence of urethral stricture.

Genotoxic effects induced by zearalenone in a human embryonic kidney cell line.

Mycotoxins are considered to be significant contaminants of food and animal feed. Zearalenone (ZEA) is a hepatotoxic mycotoxin with estrogenic and anabolic activity found in cereal grains worldwide. ZEA affects hematological and immunological parameters in humans and rodents. The compound can induce cell death, cause lipid peroxidation, inhibit protein and DNA synthesis, and exert genotoxic effects. ZEA may cause increased phagolysosomal fragility in the kidney. Our research showed that exposure of human embryonic kidney (HEK293) cells to ZEA (10 or 20µM) resulted in a concentration-dependent increase in DNA strand breaks measured with the comet assay. Damage was reduced in cells pretreated with NH4Cl, pepstatin A, or desipramine for 1h. Production of reactive oxygen species (ROS) was increased in cells exposed to ZEA, but DNA strand break induction could not be inhibited by the antioxidant hydroxytyrosol (HT). These results suggest that oxidative stress does not play a key role in DNA strand breaks induced by ZEA, that lysosomal injury precedes DNA strand breaks, and that the lysosome may be a primary target for ZEA in HEK293 cells.