Simplifying Multimodal With Single EOG Modality for Automatic Sleep Staging.

Polysomnography (PSG) recordings have been widely used for sleep staging in clinics, containing multiple modality signals (i.e., EEG and EOG). Recently, many studies have combined EEG and EOG modalities for sleep staging, since they are the most and the second most powerful modality for sleep staging among PSG recordings, respectively. However, EEG is complex to collect and sensitive to environment noise or other body activities, imbedding its use in clinical practice. Comparatively, EOG is much more easily to be obtained. In order to make full use of the powerful ability of EEG and the easy collection of EOG, we propose a novel framework to simplify multimodal sleep staging with a single EOG modality. It still performs well with only EOG modality in the absence of the EEG. Specifically, we first model the correlation between EEG and EOG, and then based on the correlation we generate multimodal features with time and frequency guided generators by adopting the idea of generative adversarial learning. We collected a real-world sleep dataset containing 67 recordings and used other four public datasets for evaluation. Compared with other existing sleep staging methods, our framework performs the best when solely using the EOG modality. Moreover, under our framework, EOG provides a comparable performance to EEG.

Facet-dependent activation of oxalic acid over hematite nanocrystals under the irradiation of visible light for efficient degradation of pollutants.

Naturally occurring hematite has been widely studied in the Fenton-like system for water pollutant remediation due to its abundance and non-toxicity. However, its inadequate catalytic activity results in difficulty in effectively degrading pollutants in the catalytic degradation system that it constitutes. Thus, we constructed a photochemical system composed of hematite with {001} facet of high activity facet and low-cost and non-toxic oxalic acid (OA) for the removal of various types of pollutants. The removal rate for the degradation of metronidazole, tetracycline hydrochloride, Rhodamine B, and hexavalent chromium by hematite nanoplate with the exposed {001} facet activating OA under visible light irradiation was 4.75, 2.25, 2.33, and 2.74 times than that by the exposed {110} facet, respectively. Density functional theory (DFT) calculation proved that the OA molecule was more easily adsorbed on the {001} facet of hematite than that on the {110} facet, which would favor the formation of the more Fe(III)-OA complex and reactive species. In addition, the reactive site of metronidazole for the attraction of radicals was identified on the basis of the DFT calculation on the molecular occupied orbitals, and the possible degradation pathway for metronidazole included carbon chain fracture, hydroxyethyl-cleavage, denitrogenation, and hydroxylation. Thus, this finding may offer a valuable direction in designing an efficient iron-based catalyst based on facet engineering for the improved activity of Fenton-like systems such as OA activation.

Narcolepsy Diagnosis With Sleep Stage Features Using PSG Recordings.

Narcolepsy is a sleep disorder affecting millions of people worldwide and causes serious public health problems. It is hard for doctors to correctly and objectively diagnose narcolepsy. Polysomnography (PSG) recordings, a gold standard for sleep monitoring and quality measurement, can provide abundant and objective cues for the narcolepsy diagnosis. There have been some studies on automatic narcolepsy diagnosis using PSG recordings. However, the sleep stage information, an important cue for narcolepsy diagnosis, has not been fully utilized. For example, some studies have not considered the sleep stage information to diagnose narcolepsy. Although some studies consider the sleep stage information, the stages are manually scored by experts, which is time-consuming and subjective. And the framework using sleep stages scored automatically for narcolepsy diagnosis is designed in a two-phase learning manner, where sleep staging in the first phase and diagnosis in the second phase, causing cumulative error and degrading the performance. To address these challenges, we propose a novel end-to-end framework for automatic narcolepsy diagnosis using PSG recordings. In particular, adopting the idea of multi-task learning, we take the sleep staging as our auxiliary task, and then combine the sleep stage related features with narcolepsy related features for our primary task of narcolepsy diagnosis. We collected a dataset of PSG recordings from 77 participants and evaluated our framework on it. Both of the sleep stage features and the end-to-end fashion contribute to diagnosis performance. Moreover, we do a comprehensive analysis on the relationship between sleep stages and narcolepsy, correlation of different channels, predictive ability of different sensing data, and diagnosis results in subject level.

2D WO3-x Nanosheet with Rich Oxygen Vacancies for Efficient Visible-Light-Driven Photocatalytic Nitrogen Fixation.

Oxygen vacancy modulation holds great promise for enhancing the photocatalytic activity for efficient nitrogen fixation under mild conditions. In this work, the two-dimensional WO3-x nanosheets with rich oxygen vacancies were prepared using solvothermal synthesis. The WO3-x nanosheets (rich oxygen vacancies) display nice photocatalytic activity for N2 reduction to ammonia with a high yield rate of 82.41 µmol·gcat-1·h-1 under irradiation of visible light (420 nm), which is 3.59 times higher than that of the WO3-x nanoparticles (poor oxygen vacancies). Electron spin resonance (ESR), N2 adsorption-desorption isotherms, and transient photocurrent responses in the N2 or Ar atmosphere experiments proved that the rich oxygen vacancies, which are induced by the nanosheet structure, could serve as active sites for the chemisorption of N2 and facilitate the electron transfer from unsaturated sites to activated N2. Moreover, based on the analysis of banding energy, the oxygen vacancies not only boosted the ability of visible light harvesting but also elevated the defect energy level to the Fermi level, further inhibiting the defect relaxation effect. The findings offer an insight into the design of the efficient photocatalysts via structure engineering and defect engineering for photocatalytic N2 fixation.

Outcomes for Hyperthermia Combined with Concurrent Radiochemotherapy for Patients with Cervical Cancer.

PURPOSE: To evaluate the effect of hyperthermia combined with concurrent radiochemotherapy (RCT) and treatment-related toxicity in patients with cervical cancer (CC) stage IB-IV. METHODS AND MATERIALS: This study was conducted between 2009 and 2013 in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IV CC. The patients were randomly assigned into 2 treatment groups: RCT and RCT plus hyperthermia (RCHT). Five-year survival, treatment-related toxicity, and other prognostic factors were evaluated. RESULTS: Three hundred seventy-three patients completed treatment and were analyzed by per-protocol (PP) analysis. The 5-year overall survival (OS) in the RCHT group (81.9%) was better than that in RCT group (72.3%), and the log-rank test showed a statistically significant difference between the 2 groups (P = .040). Univariate and multivariate Cox regression analysis for 5-year OS showed a statistically significant difference (P = .043, P = .045, respectively). The 5-year local relapse-free survival in RCHT (86.8%) was also better than that in RCT (82.7%), but the difference was not significant. Acute or late toxicity was not significantly different between the 2 groups. Advanced clinical stage (FIGO) and larger tumor size showed higher risk of death and a relatively poor prognosis in univariate and multivariate analysis. CONCLUSIONS: The study confirmed that hyperthermia combined with RCT yielded a better 5-year OS in CC. Acute and late toxicity was similar between the RCT and RCHT groups. Clinical stage (FIGO) and tumor size were independent prognostic factors in CC.

An Improved Real-Coded Genetic Algorithm Using the Heuristical Normal Distribution and Direction-Based Crossover.

A multi-offspring improved real-coded genetic algorithm (MOIRCGA) using the heuristical normal distribution and direction-based crossover (HNDDBX) is proposed to solve constrained optimization problems. Firstly, a HNDDBX operator is proposed. It guarantees the cross-generated offsprings are located near the better individuals in the population. In this way, the HNDDBX operator ensures that there is a great chance of generating better offsprings. Secondly, as iterations increase, the same individuals are likely to appear in the population. Therefore, it is possible that the two parents of participation crossover are the same. Under these circumstances, the crossover operation does not generate new individuals, and therefore does not work. To avoid this problem, the substitution operation is added after the crossover so that there is no duplication of the same individuals in the population. This improves the computational efficiency of MOIRCGA by leading it to quickly converge to the global optimal solution. Finally, aiming at the shortcoming of a single mutation operator which cannot simultaneously take into account local search and global search, a Combinational Mutation method is proposed with both local search and global search. The experimental results with sixteen examples show that the multi-offspring improved real-coded genetic algorithm (MOIRCGA) has fast convergence speed. As an example, the optimization model of the cantilevered beam structure is formulated, and the proposed MOIRCGA is compared to the RCGA in optimizing the parameters of the cantilevered beam structure. The optimization results show that the function value obtained with the proposed MOIRCGA is superior to that of RCGA.

Alantolactone enhances gemcitabine sensitivity of lung cancer cells through the reactive oxygen species-mediated endoplasmic reticulum stress and Akt/GSK3ß pathway.

Lung cancer is one of the leading causes of cancer­associated mortality in China and globally. Gemcitabine (GEM), as a first­line therapeutic drug, has been used to treat lung cancer, but GEM resistance poses a major limitation on the efficacy of GEM chemotherapy. Alantolactone (ALT), a sesquiterpene lactone compound isolated from Inula helenium, has been identified to exert anticancer activity in various types of cancer, including breast, pancreatic, lung squamous and colorectal cancer. However, the underlying mechanisms of the anticancer activity of ALT in lung cancer remain to be fully elucidated. The present study aimed to determine whether ALT enhances the anticancer efficacy of GEM in lung cancer cells and investigated the underlying mechanisms. The cell viability was assessed with a Cell Counting Kit­8 assay. The cell cycle, apoptosis and the level of reactive oxygen species (ROS) were assessed by flow cytometry, and the expression of cell cycle­associated and apoptosis­associated proteins were determined by western blot analysis. The results demonstrated that ALT inhibited cell growth and induced S­phase arrest and cell apoptosis in A549 and NCI­H520 cells. Furthermore, ALT increased the level of ROS, inhibited the Akt/glycogen synthase kinase (GSK)3ß pathway and induced endoplasmic reticulum (ER) stress in A549 and NCI­H520 cells. Additionally, ALT treatment sensitized lung cancer cells to GEM. Analysis of the molecular mechanisms further revealed that ALT enhanced the anticancer effects of GEM via ROS­mediated activation of the Akt/GSK3ß and ER stress pathways. In conclusion, combined treatment with ALT and GEM may have potential as a clinical strategy for lung cancer treatment.

miR-144 reverses cisplatin resistance in cervical cancer via targeting LHX2.

Mounting evidence showed that microRNAs involve in development and chemoresistance of various human cancers. We explored the roles and mechanisms of miR-144 in resistance to cisplatin (CDDP) of cervical cancer cells. miR-144 and LIM homeobox 2 (LHX2) expression in CDDP-resistant and the parental cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis, respectively. The functions of miR-144 overexpression on cell viability, the incidence of apoptosis, the activity of caspase-3/7, the cleaved-caspase-3 expression, cell migration, and invasion were determined in Hela cells and Hela/CDDP cells. Overexpression of miR-144 reduced cell viability, induced cell apoptosis, and inhibited cell migration and invasion after CDDP treatment. Besides, a luciferase reporter system demonstrated that miR-144 could directly bind to the 3' untranslated region (3'-UTR) of LHX2 messenger RNA (mRNA). Gain expression of miR-144 decreased the expression of LHX2 both in mRNA and protein levels. Furthermore, restoration of LHX2 partly abolished the biological functions of miR-144 in resistance of cervical cancer cells. Taken together, miR-144 overcomes resistance to CDDP via promoting cell apoptosis and inhibiting invasion through targeting LHX2 in cervical cancer cells.

Pristimerin enhances the effect of cisplatin by inhibiting the miR­23a/Akt/GSK3ß signaling pathway and suppressing autophagy in lung cancer cells.

Lung cancer is a common type of cancer with a high mortality rate in China. Cisplatin (Cis) is one of the most effective broad­spectrum chemotherapeutic drugs for the treatment of advanced lung cancer. However, Cis resistance remains an obstacle in the treatment of advanced lung cancer. Pristimerin (Pris), a naturally occurring triterpenoid quinone compound, not only possesses anticancer properties, but also enhances chemosensitivity. Therefore, the present study aimed to investigate whether Pris can enhance the chemosensitivity of lung cancer cells to Cis and identify the underlying mechanism. A Cell Counting kit­8 and flow cytometry were used to determine cell viability, cell cycle progression and apoptosis in A549 and NCI­H446 cells. Western blotting was used to determine cell apoptosis­related, cell cycle­related and autophagy­related proteins. The results showed that Pris inhibited cell proliferation, and induced G0/G1 arrest and cell apoptosis in A549 and NCI­H446 cells. The western blotting revealed that Pris effectively synergized with Cis to induce cell apoptosis by inhibiting the microRNA­23a/Akt/glycogen synthase kinase 3ß signaling pathway and suppressing autophagy. In vivo xenograft experiments confirmed that Pris effectively synergized with Cis to suppress tumor growth. Collectively, these results indicate that Pris synergized with Cis and that this may be a potential therapeutic strategy to overcome lung cancer.

Integrated Bioinformatics Analysis for Identificating the Therapeutic Targets of Aspirin in Small Cell Lung Cancer.

PURPOSE: We explored the mechanism of aspirin in SCLC by dissecting many publicly available databases. METHODS AND RESULTS: Firstly, 11 direct protein targets (DPTs) of aspirin were identified by DrugBank 5.0. Then protein-protein interaction (PPI) network and signaling pathways of aspirin DPTs were analyzed. We found that aspirin was linked with many kinds of cancer, and the most significant one is SCLC. Next, we classified the mutation of 4 aspirin DPTs in SCLC (IKBKB, NFKBIA, PTGS2 and TP53) using cBio Portal. Further, we identified top 50 overexpressed genes of SCLC by Oncomine, and the interconnected genes with the 4 aspirin DPTs in SCLC (IKBKB, NFKBIA, PTGS2 and TP53) by STRING. Lastly, we figured out 5 consistently genes as potential therapeutic targets of aspirin in SCLC. CONCLUSION: The integrated bioinformatical analysis could improve our understanding of the underlying molecular mechanism about how aspirin working in SCLC. Integrated bioinformatical analysis may be considered as a new paradigm for guiding future studies about interaction in drugs and diseases.

Kallistatin Suppresses Cell Proliferation and Invasion and Promotes Apoptosis in Cervical Cancer Through Blocking NF-κB Signaling.

Kallistatin has been recognized as an endogenous angiogenesis inhibitor and exerts pleiotropic effects in inhibiting tumor growth, migration, apoptosis, and inflammation. The purpose of the present study was to investigate the potential role and mechanisms of kallistatin in cervical cancer. We demonstrated that kallistatin effectively inhibited cell proliferation and enhanced apoptosis in a dose-dependent manner. Additionally, kallistatin suppressed migration and invasion activities and markedly reduced the expression of matrix-degrading metalloproteinases, progelatinase (MMP-2), MMP-9, and urokinase-type PA (uPA). Kallistatin reversed the epithelial-mesenchymal transition (EMT) and caused the upregulation of epithelial markers such as E-cadherin and inhibited mesenchymal markers such as N-cadherin and vimentin. Moreover, kallistatin led to a marked decrease in the expression of vascular endothelial growth factor (VEGF) and HIF-1α. In a xenograft mouse model, kallistatin treatment reduced tumor growth. Importantly, kallistatin strikingly impeded NF-κB activation by suppressing IκBα degradation and the level of phosphorylation of p65. Interestingly, similar to kallistatin, treatment with PDTC (an inhibitor of NF-κB) also attenuated cell invasion and migration. Taken together, these findings suggest that kallistatin suppresses cervical cancer cell proliferation, migration, and EMT and promotes cell apoptosis by blocking the NF-κB signaling pathway, suggesting that kallistatin may be a novel therapeutic target for cervical cancer treatment.

Peritoneal bladder fistula following radiotherapy for cervical cancer: A case report.

The occurrence of a peritoneal bladder fistula as a result of radiation cystitis following radiotherapy for cervical cancer is extremely rare and, to the best of our knowledge, has not been reported previously. The present study reports the case of a 50-year-old woman who was diagnosed with cervical cancer 20 years previously and was treated with radiotherapy. The patient was diagnosed with radiation cystitis 10 years ago, which was treated with Chinese medicine, and began experiencing sudden abdominal pain and bowel difficulties following urination 3 years ago. B-ultrasound examination at The People's Hospital of Tongchuan (Tongchuan, China) detected the presence of abdominal pelvic fluid. Following antibiotic (levofloxacin for 5 days) and ascites extraction treatment, symptoms were relieved without recurrence. However, 5 days prior to admission to the First Affiliated Hospital of Xi'an Jiatong University (Xi'an, China) on June 25, 2014, the patient experienced difficulty when urinating, abdominal pain and bloating, but did not experience frequent urination, hematuria or fever. Cystoscopic examination revealed a visible fistula on the bladder wall measuring 1×1 cm in diameter. Cytoscopic examination 1 month after catheterization and ascites extraction revealed no evidence of the fistula. The patient was followed up every 3 months for a year and a half, and is currently alive and well. In conclusion, the occurrence of peritoneal bladder fistula following radiation therapy is rare and cystoscopy is the preferred method of examination and diagnosis. Early detection and treatment may significantly improve the prognosis of patients.

The effect of interferon gamma on conventional fractionated radiation-induced damage and fibrosis in the pelvic tissue of rabbits.

We aim to investigate the effect of interferon gamma (IFN-γ) on conventional fractionated radiation-induced damage and fibrosis in ureter and colorectal mucosa. Fifty-two rabbits were randomly divided into three groups comprising a conventional radiation group, an IFN-γ group, and a control group. X-rays were used to irradiate the pelvic tissues of the rabbits in the IFN-γ and conventional radiation groups. Five days after radiation exposure, the rabbits in the IFN-γ group were administered 250,000 U/kg IFN-γ intramuscularly once a week for 5 weeks. The rabbits in the conventional radiation group received 5.0 mL/kg saline. The rabbits were sacrificed at 4, 8, 12, and 16 weeks postradiation, and the rectal and ureteral tissues within the radiation areas were collected. The results showed that the morphology of rectal and ureteral tissues was changed by X-ray radiation. The degree of damage at 4, 8, and 12 weeks, but not at 16 weeks, postradiation was significantly different between the IFN-γ and conventional radiation groups. The expression of transforming growth factor beta 1 mRNA in the ureter and colorectal mucosa of the IFN-γ group was significantly lower than that in the conventional radiation group at 4, 8, 12, and 16 weeks postradiation, but it was still higher than that in the control group. There were significant differences in the expression of collagen III among the three groups. IFN-γ can inhibit the radiation-induced upregulation of transforming growth factor beta 1 mRNA and collagen III protein in the ureter and colorectal mucosa and attenuate radiation-induced damage and fibrosis.

Time representation of mitochondrial morphology and function after acute spinal cord injury.

Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2-24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2-24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na(+)-K(+)-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged.

Cost-effectiveness of radical hysterectomy with adjuvant radiotherapy versus radical radiotherapy for FIGO stage IIB cervical cancer.

OBJECTIVE: Recent literature reports that radical hysterectomy followed by adjuvant radiotherapy has comparable progression-free survival and overall survival compared to radical radiotherapy for International Federation of Gynecology and Obstetrics stage IIB cervical cancer. Now, we evaluate the cost-effectiveness (CE) of these two treatment regimens. PRIMARY AND SECONDARY OUTCOME MEASURES: A decision-tree model was constructed comparing CE between treatment arms using the published studies for overall survival rates and treatment-related toxicity rates for 5 years. The cost data were obtained from the hospital system of the First Affiliated Hospital of Xi'an Jiaotong University. Effectiveness was measured as quality-adjusted life year (QALY). Treatment arms were compared with regard to costs and life expectancy using incremental CE ratio, and the results were presented using costs per QALY. RESULTS: The mean cost was $10,872 for radical hysterectomy followed by adjuvant radiotherapy versus $5,702 for radical radiotherapy. The incremental CE ratio for surgery-based treatment compared to radiotherapy-based treatment was -$76,453 per QALY. CONCLUSION: Radical radiotherapy would be a cost-effective method for FIGO stage IIB cervical cancer and would be favored in settings where resources are limited.

Pin1 modulates chemo-resistance by up-regulating FoxM1 and the involvements of Wnt/ß-catenin signaling pathway in cervical cancer.

The prolyl isomerase Pin1, which is frequently highly expressed in many different cancers, can directly regulate cell proliferation and the cell cycle. However, the role of Pin1 in chemo-resistance remains to be elucidated in cervical cancer. The purpose of the present study was to investigate the role of Pin1 in the chemo-resistance of cervical cancer. The cisplatin resistance was assessed using the MTT assay. Pin1, FoxM1, ß-catenin, Cyclin D1, and c-myc expression levels were detected by RT-qPCR or Western blot. The results showed that Pin1 expression displayed a similar expression pattern with the resistance to cisplatin in five cervical cell lines. Knockdown of Pin1 significantly increased the sensitivity to cisplatin in HeLa cells, while Pin1 overexpression decreased the sensitivity to cisplatin in Me180 cells. Knockdown of Pin1 significantly down-regulated FoxM1 expression in HeLa cells, while Pin1 overexpression showed a contrary effect in Me180 cells. Besides, overexpression of Pin1 markedly increased the protein expression of ß-catenin and its target genes cyclin D1 and c-myc. FoxM1 siRNA remarkably reversed the promotory effect of pcDNA-Pin1(+) on ß-catenin and its target genes cyclin D1 and c-myc in Me180 cells. Furthermore, we also found that FoxM1 siRNA and IWP-2 markedly decreased cell viability, and IWP-2 decreased cell viability to the maximum extent in the Me180 cells co-transfected with pcDNA-Pin1(+) and FoxM1 siRNA. Taken together, these data suggest that Pin1 contributes to cisplatin resistance, partly by up-regulating FoxM1 and Wnt/ß-catenin signaling pathway involved in cervical cancer.

Exendin-4 Enhances Motor Function Recovery via Promotion of Autophagy and Inhibition of Neuronal Apoptosis After Spinal Cord Injury in Rats.

Autophagy occurs prior to apoptosis and plays an important role in cell death regulation during spinal cord injury (SCI). This study aimed to determine the effects and potential mechanism of the glucagon-like peptide-1 (GLP-1) agonist extendin-4 (Ex-4) in SCI. Seventy-two male Sprague Dawley rats were randomly assigned to sham, SCI, 2.5 µg Ex-4, and 10 µg Ex-4 groups. To induce SCI, a 10-g iron rod was dropped from a 20-mm height to the spinal cord surface. Ex-4 was administered via intraperitoneal injection immediately after surgery. Motor function evaluation with the Basso Beattie Bresnahan (BBB) locomotor rating scale indicated significantly increased scores (p < 0.01) in the Ex-4-treated groups, especially 10 µg, which demonstrated the neuroprotective effect of Ex-4 after SCI. The light chain 3-II (LC3-II) and Beclin 1 protein expression determined via western blot and the number of autophagy-positive neurons via immunofluorescence double labeling were increased by Ex-4, which supports promotion of autophagy (p < 0.01). The caspase-3 protein level and neuronal apoptosis via transferase UTP nick end labeling (TUNEL)/NeuN/DAPI double labeling were significantly reduced in the Ex-4-treated groups, which indicates anti-apoptotic effects (p < 0.01). Finally, histological assessment via Nissl staining demonstrated the Ex-4 groups exhibited a significantly greater number of surviving neurons and less cavity (p < 0.01). To our knowledge, this is the first study to indicate that Ex-4 significantly enhances motor function in rats after SCI, and these effects are associated with the promotion of autophagy and inhibition of apoptosis.

A Randomized Controlled Trial Comparing Clinical Outcomes and Toxicity of Lobaplatin- Versus Cisplatin-Based Concurrent Chemotherapy Plus Radiotherapy and High-Dose-Rate Brachytherapy for FIGO Stage II and III Cervical Cancer.

BACKGROUND: We designed this randomized controlled trial (RCT) to assess whether lobaplatin-based concurrent chemotherapy might be superior to cisplatin-based concurrent chemotherapy for FIGO stage II and III cervical cancer in terms of efficacy and safety. MATERIALS AND METHODS: This prospective, open-label RCT aims to enroll 180 patients with FIGO stage II and III cervical cancer, randomly allocated to one of the three treatment groups (cisplatin 15mg/m2, cisplatin 20mg/m2 and lobaplatin 35mg/m2), with 60 patients in each group. All patients will receive external beam irradiation (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT). Patients in cisplatin 15mg/m2 and 20mg/m2 groups will be administered four cycles of 15mg/m2 or 20mg/m2 cisplatin intravenously once weekly from the second week to the fifth week during EBRT, while patients inthe lobaplatin 35mg/m2 group will be administered two cycles of 35mg/m2 lobaplatin intravenously in the second and fifth week respectively during pelvic EBRT. All participants will be followed up for at least 12 months. Complete remission rate and progression-free survival (PFS) will be the primary endpoints. Overall survival (OS), incidence of adverse events (AEs), and quality of life will be the secondary endpoints. RESULTS: Between March 2013 and March 2014, a total of 61 patients with FIGO stage II and III cervical cancer were randomly assigned to cisplatin 15mg/m2 group (n=21), cisplatin 20mg/m2 group (n=21) and lobaplatin 35mg/m2 group (n=19). We conducted a preliminary analysis of the results. Similar rates of complete remission and grades 3-4 gastrointestinal reactions were observed for the three treatment groups (P=0.801 and 0.793, respectively). Grade 3-4 hematologic toxicity was more frequent in the lobaplatin group than the cisplatin group. CONCLUSIONS: This proposed study will be the first RCT to evaluate whether lobaplatin-based chemoraiotherapy will have beneficial effects, compared with cisplatin-based chemoradiotherapy, on complete remission rate, PFS, OS, AEs and quality of life for FIGO stage II and III cervical cancer.

Application of 1H NMR spectroscopy-based metabonomics to feces of cervical cancer patients with radiation-induced acute intestinal symptoms.

OBJECTIVE: Radiation-induced acute intestinal symptoms (RIAISs) are a common complication of radiotherapy for cervical cancer. The aim of this study was to use (1)H nuclear magnetic resonance ((1)H NMR) combined with chemometric analysis to develop a metabolic profile of patients with RIAISs. METHODS: Fecal samples were collected from 66 patients with cervical cancer before and after pelvic radiotherapy. After radiotherapy, RIAISs occurred in eleven patients. We selected another 11 patients from participants without RIAISs whose age, stage, histological type and treatment methods are matched with RIAIS patients as the control group. (1)H NMR spectroscopy combined with multivariate pattern recognition analysis was used to generate metabolic profile data, as well as to establish a RIAIS-specific metabolic phenotype. RESULTS: Orthogonal partial least-squares discriminant analysis was used to distinguish samples between the pre- and post-radiotherapy RIAIS patients and between RIAIS patients and controls. Fecal samples from RIAIS patients after pelvic radiotherapy were characterized by increased concentrations of α-ketobutyrate, valine, uracil, tyrosine, trimethylamine N-oxide, phenylalanine, lysine, isoleucine, glutamine, creatinine, creatine, bile acids, aminohippurate, and alanine, accompanied by reduced concentrations of α-glucose, n-butyrate, methylamine, and ethanol relative to samples from RIAIS patients before pelvic radiotherapy, while in RIAIS patients relative to controls, trimethylamine, n-butyrate, fumarate and acetate were down-regulated and valine, TMAO, taurine, phenylalanine, lactate, isoleucine and creatinine were up-regulated. CONCLUSIONS: We obtained the metabolic profile of RIAIS patients from fecal samples using NMR-based metabonomics. This profile has the potential to be developed into a novel clinical tool for RIAIS diagnosis or therapeutic monitoring, and could contribute to an improved understanding of the disease mechanism. However, because of the limitations of methods, technique, bacterial contamination of feces and small sample size, further research and verification are needed.

Neuroprotective effects of exendin-4 in rat model of spinal cord injury via inhibiting mitochondrial apoptotic pathway.

Spinal cord injury (SCI) is a devastating problem of health. Glucagon-like peptide-1 (GLP-1) is glucose-dependent insulinotropic hormone. Exendin-4 is the longacting GLP-1 receptor agonist that used as an anti-diabetic drug. Recent studies demonstrated exendin-4 has a series of beneficial neuroprotective properties. This study was designed to assess the neuroprotective effects of exendin-4 against spinal cord injury. 72 rats were randomly divided into three groups as follows: sham operation group, SCI group, and exendin-4 group (intraperitoneal injection of exendin-4 at 10 µg/rat immediately after SCI). First, a decrease of malodialdehyde (MDA) levels and an increase of glutathione (GSH) levels in the exendin-4 group demonstrated the anti-oxidation effect of exendin-4. Further, the preservation of mitochondrial membrane potential (ΔΨm) and the reduction of cytochrome c release suggested the protection for mitochondria. Moreover, a decline of the expression level of Bax, Bcl-2 and caspase-3 and the results of TUNEL staining indicated its anti-apoptosis role. Finally, behavioral assessment with Basso Beattle Bresnahan locomotor rating scale (BBB) showed that animals in exendin-4 group achieved a significant increase in BBB scores. Our results suggest that exendin-4 prevents against SCI-induced mitochondrial apoptotic pathway and contributes to functional improvement after SCI.