Search

Background: Colorectal polyps, which are characterized by a high recurrence rate, represent preneoplastic conditions of the intestine. Due to unclear mechanisms of pathogenesis, first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection. Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps, the exact compositions and roles of bacteria in the mucosa around the lesions, rather than feces, remain unsettled., Aim: To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps., Methods: Mucosal samples were collected from four patients consistently with adenomatous polyps (Ade), seven consistently with non-Ade (Pol), ten with current Pol but previous Ade, and six healthy individuals, and bacterial patterns were evaluated by 16S rDNA sequencing. Linear discriminant analysis and Student's t -tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes. Pearson's correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators., Results: The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals. These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps, but also existed in histologically normal tissue 10 cm distal from the lesions. Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions, Pol, and Ade. Increased abundance of Gram-negative bacteria, including Klebsiella , Plesiomonas , and Cronobacter , was observed in Pol group and Ade group, suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment. Meanwhile, age and gender were linked to bacteria changes, indicating the potential involvement of sex hormones., Conclusion: These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps, especially adenoma. Targeting specific pathogenic bacteria may attenuate the recurrence of polyps., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To investigate whether T2-weighted imaging (T2WI)-based intratumoral and peritumoral radiomics can predict extranodal extension (ENE) and prognosis in patients with resectable rectal cancer., Methods: One hundred sixty-seven patients with resectable rectal cancer including T3T4N + cases were prospectively included. Radiomics features were extracted from intratumoral, peritumoral 3 mm, and peritumoral-mesorectal fat on T2WI images. Least absolute shrinkage and selection operator regression were used for feature selection. A radiomics signature score (Radscore) was built with logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each Radscore. A clinical-radiomics nomogram was constructed by the most predictive radiomics signature and clinical risk factors. A prognostic model was constructed by Cox regression analysis to identify 3-year recurrence-free survival (RFS)., Results: Age, cT stage, and lymph node-irregular border and/or adjacent fat invasion were identified as independent clinical risk factors to construct a clinical model. The nomogram incorporating intratumoral and peritumoral 3 mm Radscore and independent clinical risk factors achieved a better AUC than the clinical model in the training (0.799 vs. 0.736) and validation cohorts (0.723 vs. 0.667). Nomogram-based ENE (hazard ratio [HR] = 2.625, 95% CI = 1.233-5.586, p = 0.012) and extramural vascular invasion (EMVI) (HR = 2.523, 95% CI = 1.247-5.106, p = 0.010) were independent risk factors for predicting 3-year RFS. The prognostic model constructed by these two indicators showed good performance for predicting 3-year RFS in the training (AUC = 0.761) and validation cohorts (AUC = 0.710)., Conclusion: The nomogram incorporating intratumoral and peritumoral 3 mm Radscore and clinical risk factors could predict preoperative ENE. Combining nomogram-based ENE and MRI-reported EMVI may be useful in predicting 3-year RFS., Critical Relevance Statement: A clinical-radiomics nomogram could help preoperative predict ENE, and a prognostic model constructed by the nomogram-based ENE and MRI-reported EMVI could predict 3-year RFS in patients with resectable rectal cancer., Key Points: • Intratumoral and peritumoral 3 mm Radscore showed the most capability for predicting ENE. • Clinical-radiomics nomogram achieved the best predictive performance for predicting ENE. • Combining clinical-radiomics based-ENE and EMVI showed good performance for 3-year RFS., (© 2024. The Author(s).)

Toxoplasma gondii infection in pregnant women may cause fetal anomalies; however, the underlying mechanisms remain unclear. The current study investigated whether T. gondii induces pyroptosis in human placental cells and the underlying mechanisms. Human placental trophoblast (BeWo and HTR-8/SVneo) and amniotic (WISH) cells were infected with T. gondii, and then reactive oxygen species (ROS) production, cathepsin B (CatB) release, inflammasome activation, and pyroptosis induction were evaluated. The molecular mechanisms of these effects were investigated by treating the cells with ROS scavengers, a CatB inhibitor, or inflammasome-specific siRNA. T. gondii infection induced ROS generation and CatB release into the cytosol in placental cells but decreased mitochondrial membrane potential. T. gondii-infected human placental cells and villi exhibited NLRP1, NLRP3, NLRC4, and AIM2 inflammasome activation and subsequent pyroptosis induction, as evidenced by increased expression of ASC, cleaved caspase-1, and mature IL-1β and gasdermin D cleavage. In addition to inflammasome activation and pyroptosis induction, adverse pregnancy outcome was shown in a T. gondii-infected pregnant mouse model. Administration of ROS scavengers, CatB inhibitor, or inflammasome-specific siRNA into T. gondii-infected cells reversed these effects. Collectively, these findings show that T. gondii induces NLRP1/NLRP3/NLRC4/AIM2 inflammasome-dependent caspase-1-mediated pyroptosis via induction of ROS production and CatB activation in placental cells. This mechanism may play an important role in inducing cell injury in congenital toxoplasmosis., Competing Interests: Disclosure Statement None declared., (Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Background: Folic acid (FA) supplementation is associated with a lower risk of the neural tube and heart defects and is recommended for women of childbearing age. Although there are detailed recommendations, differences in the initiation time and duration of FA supplementation remain poorly studied., Methods: A multicentre prospective study of 17,713 women was conducted. The incidence of congenital malformations in women taking a recommended dosage (e.g. 0.4 or 0.8 mg/day) of FA was compared with that in women without supplementation. The predicted probability of malformations by the initiation time and duration of FA use was estimated to determine optimal options., Results: Periconceptional FA supplementation was associated with a lower and insignificant risk of congenital malformations (1.59% vs. 2.37%; odds ratio [OR] 0.69; 95% confidence interval [CI]: 0.44-1.08), heart defects (3.8 vs. 8.0 per 1000 infants; OR, 0.47; 0.21-1.02), and neural tube defects (7.0 vs. 11.5 per 10,000 infants; OR, 0.64; 0.08-5.15). FA use after pregnancy provided greater protection against total malformations. Statistically significant associations were found in women who initiated FA supplementation in the first month of gestation (OR, 0.55; 95% CI: 0.33-0.91) and in those who supplemented for 1 to 2 months (OR, 0.59; 95% CI: 0.36-0.98). Similar results were found for heart defects. The optimal initiation time was 1.5 (optimal range: 1.1 to 1.9) months before pregnancy and a duration of 4.0 (3.7 to 4.4) months was reasonable to achieve the lowest risk of congenital malformations. Heart defect prevention required an earlier initiation (2.2 vs. 1.1 months before pregnancy) and a longer duration (4.7 vs. 3.7 months) than the prevention of other malformations., Conclusions: The timely initiation of FA supplementation for gestation was associated with a decreased risk of congenital malformations, which was mainly attributed to its protection against heart defects. The initiation of FA supplementation 1.5 months before conception with a duration of 4 months is the preferred option for congenital malformation prevention., Trial Registration: Chictr.org.cn identifier: ChiCTR-SOC-17010976., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: High signals on diffusion weighted imaging along the corticomedullary junction (CMJ) have demonstrated excellent diagnostic values for adult-onset neuronal intranuclear inclusion disease (NIID). However, the longitudinal course of diffusion weighted imaging high intensities in adult-onset NIID patients has rarely been investigated., Methods: We described four NIID cases that had been discovered using skin biopsy and NOTCH2NLC gene testing, after diffusion weighted imaging exhibiting the distinctive corticomedullary junction high signals. Then using complete MRI data from NIID patients, we analyzed the chronological diffusion weighted imaging alterations of those individuals that had been published in Pub Med., Results: We discussed 135 NIID cases with comprehensive MRI data, including our four cases, of whom 39 had follow-up outcomes. The following are the four primary diffusion weighted imaging dynamic change patterns: (1) high signal intensities in the corticomedullary junction were negative on diffusion weighted imaging even after an 11-year follow-up (7/39); (2) diffusion weighted imagings were initially negative but subsequently revealed typical findings (9/39); (3) high signal intensities vanished during follow-up (3/39); (4) diffusion weighted imagings were positive at first and developed in a step-by-step manner (20/39). We discovered that NIID lesions eventually damaged the deep white matter, which comprises the cerebral peduncles, brain stem, middle cerebellar peduncles, paravermal regions, and cerebellar white matter., Conclusion: The longitudinal dynamic changes in NIID of diffusion weighted imaging are highly complex. We find that there are four main patterns of dynamic changes on diffusion weighted imaging. Furthermore, as the disease progressed, NIID lesions eventually involved the deep white matter., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Chen, Tan, Yin, Li and Wang.)

Objective: To investigate the characteristics of salivary microbiota in patients with laryngopharyngeal reflux (LPR). Methods: A case-control study was applied to enroll 60 patients and healthy subjects who were outpatients of the Department of Otorhinolaryngology Head and Neck Surgery of the Eighth Medical Center of the PLA General Hospital from December 2020 to March 2021, including 35 males and 25 females, aged from 21 to 80 (33.75±11.10) years. Thirty patients with suspected laryngopharyngeal reflux were selected as study group and thirty healthy volunteers without pharyngeal symptoms were selected as control group. Their salivary samples were collected, and the salivary microbiota was detected and analyzed by 16S rDNA sequencing. SPSS 18.0 software was used for statistical analysis. Results: There was no significant difference in the diversity of salivary microbiota between the two groups. At the phylum classification level, the relative abundance of Bacteroidetes in the study group was higher than that in the control group[37.86(31.15, 41.54)% vs 30.24(25.51, 34.18)%, Z =-3.46, P< 0.01]. And the relative abundance of Proteobacteria in the study group was lower than that in the control group [15.76(11.81, 20.17)% vs 20.63(13.98, 28.82)%, Z =-1.98, P< 0.05]. At the genus level, the relative abundance of Prevotella , Lactobacillus , Parascardovia and Sphingobium in the study group was higher than that in the control group( Z values were-2.92, -2.69, -2.05, -2.31, respectively, P <0.05).And the relative abundance of Streptococcus , Cardiobacterium , Klebsiella and Uruburuella of study group was lower than that of control group( Z values were -2.43, -2.32, -2.17, -2.32, respectively, P <0.05). LEfSe difference analysis showed that there were 39 bacteria with significant differences between the two groups, including Bacteroidetes, Prevotellaceae and Prevotella , which were enriched in the study group, and Streptococcaceae, Streptococcus and other taxa, which were enriched in the control group( P <0.05). Conclusion: The changes of the microflora in the saliva between LPR patients and healthy people suggest that the dysbacteriosis might exist in LPR patients, which may play an important role in the pathogenesis and development of LPR.

Purpose: To build computed tomography enterography (CTE)-based multiregional radiomics model for distinguishing Crohn's disease (CD) from intestinal tuberculosis (ITB)., Materials and Methods: A total of 105 patients with CD and ITB who underwent CTE were retrospectively enrolled. Volume of interest segmentation were performed on CTE and radiomic features were obtained separately from the intestinal wall of lesion, the largest lymph node (LN), and region surrounding the lesion in the ileocecal region. The most valuable radiomic features was selected by the selection operator and least absolute shrinkage. We established nomogram combining clinical factors, endoscopy results, CTE features, and radiomic score through multivariate logistic regression analysis. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the prediction performance. DeLong test was applied to compare the performance of the models., Results: The clinical-radiomic combined model comprised of four variables including one radiomic signature from intestinal wall, one radiomic signature from LN, involved bowel segments on CTE, and longitudinal ulcer on endoscopy. The combined model showed good diagnostic performance with an area under the ROC curve (AUC) of 0.975 (95% CI 0.953-0.998) in the training cohort and 0.958 (95% CI 0.925-0.991) in the validation cohort. The combined model showed higher AUC than that of the clinical model in cross-validation set (0.958 vs. 0.878, P = 0.004). The DCA showed the highest benefit for the combined model., Conclusion: Clinical-radiomic combined model constructed by combining CTE-based radiomics from the intestinal wall of lesion and LN, endoscopy results, and CTE features can accurately distinguish CD from ITB., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The potential teratogenic risk of traditional Chinese medicine (TCM) is of widespread concern; however, related evidence is largely absent in humans. This study aimed to compare the prevalence of congenital malformations between pregnant women with and without TCM exposure., Material and Methods: This was a multicenter prospective cohort study of 17 713 women who participated in a survey on periconceptional TCM exposure. Primary outcome was congenital malformations diagnosed from a survey conducted on the day 42 after delivery., Results: A total of 16 751 pregnant women with 273 congenital malformations were included in the analysis. Fetuses exposed to TCM had an increased risk of congenital malformations compared to those without exposure (odds ratio [OR] 2.10; 95% confidence interval [CI] 1.09-4.02) after controlling for potential confounders. There were significant associations with congenital malformations in women with early pregnant exposure (OR 2.04, 95% CI 1.00-4.20) and for those who received ≥2 TCM formulas (OR 5.84, 95% CI 1.44-23.65). Pre-pregnancy TCM exposure was significantly associated with an increased risk of congenital heart defects (OR 12.69; 95% CI 3.01-53.51)., Conclusions: Periconceptional TCM exposure is associated with an increased risk of congenital malformation. This effect was cumulative and sensitive to periconceptional age. Therefore, TCM deserves more attention and should be used cautiously for pregnant women and those trying to become pregnant., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 ( OR =0.41, 95% CI: 0.21-0.79, P =0.008), rs579408( OR =1.54, 95% CI: 1.03-2.29, P =0.034) and rs543923 ( OR =0.63, 95% CI: 0.41-0.98, P =0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 ( OR =0.55, 95% CI: 0.33-0.91, P =0.020) and GSDME rs2954558 ( OR =1.52, 95% CI: 1.01-2.31, P =0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 ( OR =0.36, 95% CI: 0.16-0.83, P =0.017), GSDME rs12540919 ( OR =0.52, 95% CI: 0.27-0.99, P =0.045) and NLRP3 rs3806268 ( OR =1.51, 95% CI: 1.03-2.22, P =0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P >0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P <0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

Objective: To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI)., Methods: The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed., Results: The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M 2 ). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections., Conclusion: Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.

At present, there are widespread financing difficulties in China's trade circulation industry. Supply chain finance can provide financing for small- and medium-sized enterprises in China's trade circulation industry, but it will produce financing risks such as credit risks. It is necessary to analyze the causes of the risks in the supply chain finance of the trade circulation industry and measure these risks by establishing a credit risk assessment system. In this article, a supply chain financial risk early warning index system is established, including 4 first-level indicators and 29 third-level indicators. Then, on the basis of the supply chain financial risk early warning index system, combined with the method of convolution neural network, the supply chain financial risk early warning model of trade circulation industry is constructed, and the evaluation index is measured by the method of principal component analysis. Finally, the relevant data of trade circulation enterprises are selected to make an empirical analysis of the model. The conclusion shows that the supply chain financial risk early warning model and risk control measures established in this article have certain reference value for the commercial circulation industry to carry out supply chain finance. It also provides guidance for trade circulation enterprises to deal with supply chain financial risks effectively., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Li-Li Yin et al.)

This study is to investigate optimum apparent diffusion coefficient (ADC) parameter for predicting lymphovascular invasion (LVI), lymph node metastasis (LNM) and histology type in resectable rectal cancer. 58 consecutive patients with resectable rectal cancer were retrospectively identified. The minimum, maximum, average ADC and ADC difference value were obtained on ADC maps. Maximum ADC and ADC difference value increased with the appearance of LVI (r = 0.501 and 0.495, P < 0.001, respectively) and development of N category (r = 0.615 and 0.695, P < 0.001, respectively). ADC difference value tended to rise with lower tumor differentiation (r = - 0.269, P = 0.041). ADC difference value was an independent risk factor for predicting LVI (odds ratio = 1.323; P = 0.005) and LNM (odds ratio = 1.526; P = 0.005). Maximum ADC and ADC difference value could distinguish N0 from N1 category, N0 from N1-N2, N0-N1 from N2 (all P < 0.001). Only ADC difference value could distinguish histology type (P = 0.041). ADC difference value had higher area under the receiver operating characteristic curve than maximum ADC in identifying LVI (0.828 vs 0.797), N0 from N1 category (0.947 vs 0.847), N0 from N1-N2 (0.935 vs 0.874), and N0-N1 from N2 (0.814 vs 0.770). ADC difference value may be superior to the other ADC value parameters to predict LVI, N category and histology type of resectable rectal cancer.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA SNHG16 functions as an oncogene by sponging miR-200a-3p in pancreatic cancer, by J.-Q. Guo, Z.-J. Yang, S. Wang, Z.-Z. Wu, L.-L. Yin, D.-C. Wang, published in Eur Rev Med Pharmacol Sci 2020; 24 (4): 1718-1724-DOI: 10.26355/eurrev&#95;202002&#95;20347-PMID: 32141539" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20347.

The systematic breeding method was adopted to breed a new good cultivar of Curcuma longa, named &quot;Chuanjianghuang 1&quot;. From 2014 to 2015, two consecutive years of multi-point test were carried out in Shuangliu, Chongzhou and Wenjiang. The biological characters, phenology, agronomic characters, yield and quality indexes of &quot;Chuanjianghuang 1&quot; were comprehensively evaluated. The results showed that compared with local traditional species, the rhizome yield of the new cultivar &quot;Chuanjianghuang 1&quot; increased by 20.61%.The average content of volatile oil was higher than 24.17% and the average content of curcumin in root tuber was higher than 26.62%. The yield of root tuber increased by 54.59%.The average content of volatile oil is higher than 36.28% and the average content of curcuminoids is higher than 25.31%. Compared with &quot;Huangsi Yujin 1&quot;, &quot;Chuanjianghuang 1&quot; increased the average yield of rhizome by 123.68%,the volatile oil increased by an average of 7.69%and the curcumin content increased by an average of 58.23%. The average content of volatile oil is higher than 52.82% and the average content of curcuminoids in root tuber was higher than 38.34%. The new variety &quot;Chuanjianghuang 1&quot; has better yield than the local traditional species, and the internal quality of rhizome and root tuber is better. Compared with &quot;Huangsi Yujin 1&quot;, the yield of rhizome is significantly increased, and the internal quality of rhizome and root tuber is better, especially the content of curcumin in rhizome and curcuminoids in root tuber is significantly higher than that of &quot;Huangsi Yujin 1&quot;. &quot;Chuanjianghuang 1&quot; is high yield, good quality, good stability and strong adaptability, which is suitable for cultivation and promotion in Chengdu Jinma River Basin, such as Shuangliu, Chongzhou, Wenjiang.

Objective: To investigate the associations between the genetic variations of apoptosis genes and the adverse events of postoperative concurrent chemoradiotherapy in patients with rectal cancer. Methods: We enrolled 362 patients with stage Ⅱ to Ⅲ rectal cancer who received concurrent chemoradiotherapy. Whole blood sample (2 ml) was collected from patient at the time of enrollment before therapy. Sequenom MassARRAY was used to detect the genotypes of 29 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight apoptosis genes, including Fas cell surface death receptor(FAS), Fas ligand(FASL), apoptotic peptidase activating factor 1(APAF1), BCL2 associated X(BAX), TNF-related apoptosis-inducing ligand(TRAIL), TNF-related apoptosis-inducing ligand receptor 1(TRAILR1), TNF-related apoptosis-inducing ligand receptor 2(TRAILR2) and caspase-7(CASP7). The associations between genotypes and adverse events of chemoradiotherapy were measured by unconditional logistic regression model. Results: Three hundred and sixty two patients were treated with total mesorectal excision surgery followed by a total radiation dose of 50 Gy applied in 25 fractions over a period of 5 weeks concurrently with daily administration of capecitabine (1 600 mg/m(2) per day, continuously for 2 weeks and taking a week off every 21-day cycle). One hundred and six patients (29.3%) had grade≥2 myelosuppression. Three SNPs associated with the risk of grade ≥2 myelosuppression included FAS rs1468063 ( OR =1.51, 95% CI: 1.07-2.15, P =0.020), APAF1 rs11296996 ( OR =0.69, 95% CI: 0.49-0.98, P =0.039) and BAX rs4645904 ( OR =0.69, 95% CI: 0.50-0.97, P =0.030). One hundred and sixty one patients (44.5%) developed grade≥2 diarrhea. Five SNPs that significantly associated with risk of grade≥2 diarrhea included APAF1 rs11296996 ( OR =1.42, 95% CI: 1.02-2.00, P =0.040), rs74619561 ( OR =2.16, 95% CI: 1.27-3.68, P =0.005), CASP7 rs12263370 ( OR =1.67, 95% CI: 1.05-2.66, P =0.029), rs12247479 ( OR =1.85, 95% CI: 1.12-3.08, P =0.017) and TRAIL rs112822654 ( OR =0.68, 95% CI: 0.48-0.96, P =0.027). The remaining SNPs were not related to the adverse events of chemoradiotherapy (all P >0.05). Grade≥2 myelosuppression occurred less frequently in male than in female ( P =0.046); Surgical treatment and tumor location had great impact on the occurrence of grade≥2 diarrhea (all P <0.001) and dermatitis (all P <0.05). Conclusions: The genetic variations of FAS, APAF1, BAX, TRAIL and CASP7 are related to the adverse events of concurrent chemoradiotherapy in patients with rectal cancer, which may be potential genetic biomarkers for individualized treatment of rectal cancer.

Protein design is able to create artificial proteins with advanced functions, and computer simulation plays a key role in guiding the rational design. In the absence of structural evidence for cytoglobin (Cgb) with an intramolecular disulfide bond, we recently designed a de novo disulfide bond in myoglobin (Mb) based on structural alignment (i.e., V21C/V66C Mb double mutant). To provide deep insight into the regulation role of the Cys21-Cys66 disulfide bond, we herein perform molecular dynamics (MD) simulation of the fluoride-protein complex by using a fluoride ion as a probe, which reveals detailed interactions of the fluoride ion in the heme distal pocket, involving both the distal His64 and water molecules. Moreover, we determined the kinetic parameters of fluoride binding to the double mutant. The results agree with the MD simulation and show that the formation of the Cys21-Cys66 disulfide bond facilitates both fluoride binding to and dissociating from the heme iron. Therefore, the combination of theoretical and experimental studies provides valuable information for understanding the structure and function of heme proteins, as regulated by a disulfide bond. This study is thus able to guide the rational design of artificial proteins with tunable functions in the future.

Pig leg weakness not only causes huge economic losses for producers but also affects animal welfare. However, genes with large effects on pig leg weakness have not been identified and suitable methods to study porcine leg weakness are urgently needed. Bone mineral density (BMD) is an important indicator for determining leg soundness in pigs. Increasing pig BMD is likely to improve pig leg soundness. In this study, porcine BMD was measured using an ultrasound bone densitometer in a population with 212 Danish Landrace pigs and 537 Danish Yorkshires. After genotyping all the individuals using GeneSeek Porcine 50K SNP chip, genetic parameter estimation was performed to evaluate the heritability of BMD. Genome-wide association study and haplotype analysis were also performed to identify the variants and candidate genes associated with porcine BMD. The results showed that the heritability of BMD was 0.21 in Landrace and 0.31 in Yorkshire. Five single-nucleotide polymorphisms on chromosome 6 identified were associated with porcine BMD at suggestive significance level. Two candidate quantitative trait loci (74.47 to 75.33 Mb; 80.20 to 83.83 Mb) and three potential candidate genes (ZBTB40, CNR2, and Lin28a) of porcine BMD were detected in this study., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science.)

The effects of the immediate early response 5 ( IER5 ) gene on the sensitivity of HeLa cells to radiation remain unclear. In the present study, stably transfected HeLa cells resulting in the knockdown or overexpression of IER5 were investigated. In addition, xenografts of normal, IER5 -silenced and -overexpressed HeLa cells were injected into nude mice and examined. The results demonstrated that the radiosensitivity of the IER5 -overexpressed HeLa cells was significantly increased compared with that of the normal and IER5 -silenced cells. The upregulation of IER5 effectively decreased cell proliferation and IER5 silencing promoted cell proliferation compared with that in the normal HeLa cells. Following irradiation of the cells with IER5 knockdown, cell cycle was arrested at the G 2 /M phase and an increase in the proportion of S phase cells was observed. By contrast, the overexpression of IER 5 led to an increase in the proportion of G 1 phase cells. Furthermore, the upregulation of IER5 inhibited tumor growth in vivo . The present findings demonstrate that the IER5 gene affects the radiosensitivity of HeLa cells and serves an important role in cell proliferation, suggesting that this gene may be a potential radiotherapeutic target in cervical cancer.

OBJECTIVE. The purpose of this study was to assess whether MR volumetric data on DW and T2-weighted MR images are correlated with lymphovascular invasion and lymph node metastases in resectable rectal cancer. MATERIALS AND METHODS. This retrospective study consisted of 50 consecutive patients with rectal cancer who underwent radical surgery within 1 week of MRI. The gross tumor volume was determined on both diffusion-weighted and T2-weighted MR images and correlated with pathologic lymphovascular invasion and lymph node metastases using univariate, multivariate, and ROC curve analyses. RESULTS. Both gross tumor volume values showed correlations with lymphovascular invasion ( r = 0.750 vs r = 0.710; p < 0.0001) and lymph node metastases ( r = 0.780 vs r = 0.755; p < 0.0001). Both values were associated with lymphovascular invasion and lymph node metastases in univariate analysis (all p < 0.0001), whereas only the DWI-based value was an independent risk factor for lymphovascular invasion (odds ratio = 1.207; p = 0.005) and lymph node metastases (odds ratio = 1.420; p = 0.005) in multivariate analysis. Both values could distinguish between N0 and N1, N0 and N1-N2, and N0-N1 and N2 disease (all p < 0.0001) in the Mann-Whitney U test. The area under the ROC curve was higher for the DWI-based value in lymphovascular invasion (0.899 vs 0.877), N0 vs N1 (0.865 vs 0.827), N0 vs N1-N2 (0.934 vs 0.911), and N0-N1 vs N2 (0.932 vs 0.927). CONCLUSION. Tumor volumetry data correlated with both lymphovascular invasion and lymph node metastases in resectable rectal cancer. In particular, the DWI-based gross tumor volume showed the most potential for noninvasive preoperative evaluation of lymphovascular invasion and lymph node metastases.

Objective: To investigate the associations between genetic variations of DNA polymerase kappa (POLK) and treatment response to platinum-based chemotherapy of small cell lung cancer (SCLC), and to analyze the influencing factors on survival. Methods: Five haplotype-tagging single nucleotide polymorphisms (htSNPs) of POLK were genotyped by Sequenom MassARRAY methods in 1 030 SCLC patients who received platinum-based chemotherapy, and had different response and survival time. The associations between SNPs and treatment response were analyzed by computing the odds ratios ( ORs ) and 95% confidence intervals ( CIs ) from logistic regression model. Cox regression was used for survival analysis between SNPs and overall survival by computing the hazard ratios ( HRs ) and 95% CIs . Results: Among 1 030 cases, 558 (54.2%) cases received cis-platinum and etoposide treatment while others treated with carboplatin and etoposide. Seven hundred and eighty eight patients were chemotherapy responders in the study with a response rate of 76.5%. The median follow-up time of these patients was 22.0 months. Patients were followed up to get their survival information. The median survival time of these patients was 22.5 months. Six hundred and seventy three patients (65.3%) had died by the last date of follow-up to get their survival information (Dec 21, 2017). Five htSNPs of POLK were not associated with the chemotherapy response of SCLC patients who received platinum-based chemotherapy (all P >0.05). Multivariate Cox proportional hazards regression model analysis showed that, rs73120833 of POLK was significantly associated with the overall survival (OS) of SCLC patients, compared with POLK rs73120833 T allele, C allele can prolong OS (adjusted HR =0.87, 95% CI =0.77-0.97, P =0.021). The remaining 4 SNPS, including rs10077427, rs3756558, rs4549504 and rs5744545, were not significantly associated with overall survival. Age≤56, KPS> 80, limited-stage, chemotherapy response and radiation therapy can remarkably prolong OS (all P <0.05). Conclusion: These results suggest that POLK genetic polymorphism rs73120833 plays an important role on the prognosis of SCLC patients, which can be potential genetic biomarker for SCLC personalized treatment.

RBM10 regulates the expression of various genes, which are often mutated in male lung adenocarcinoma. The present study confirmed the association of the RBM10 mutation at exon 10 with the clinicopathological data and prognosis of lung adenocarcinoma. The effect of mutant RBM10 on regulating lung cancer cell growth and invasion was investigated in vitro . Tissue specimens from 50 patients with lung adenocarcinoma were subjected to Sanger sequencing for RBM10 exon 10 mutations. Lung adenocarcinoma cells were transfected with pcDNA3.1 carrying wild type RBM10 cDNA or exon mutation cDNA for cell viability, apoptosis and invasion assays. RBM10 exon 10 mutations were identified in 11 out of 50 patients, with a high frequency in male patients [c.763 C>T, p.Arg241Cys for 33.3% (10/30)] and were significantly associated with the American Joint Committee on Cancer stage (P=0.005), lymph node metastasis (P=0.019) and shorter 5-year survival rate compared with the wild type RBM10 (36.4% vs. 46.5%; P=0.019). Multivariate analysis revealed that RBM10 exon 10 mutation was an independent prognostic factor (HR=3.787; P=0.033). RBM10 exon 10 mutation at c.763 C>T significantly promoted tumor cell proliferation and invasion capacity, whereas wild type RBM10 inhibited tumor cell invasion in vitro . In conclusion, RBM 10 mutation at exon 10 (c.763 C>T) occurs frequently and is an independent prognostic predictor in lung adenocarcinoma.

Objective: Although Tantalum (Ta) exhibits better osteoinductivity in healthy subjects when compared with titanium (Ti), the relative effects in osteoporosis remain unknown., Materials and Methods: In this study, bone mesenchymal stromal cells of ovariectomized rats (OVX-rBMSCs) were seeded on Ta and Ti substrates for in vitro evaluation of cell viability, reactive oxygen species (ROS) production, alkaline phosphatase (ALP) activity, extracellular mineralization osteogenic gene and protein expression involved in bone morphogenetic protein (BMP2)/small mothers against decapentaplegic homologs 1 (Smad1) pathway. For in vivo assessment, Ta and Ti implants were embedded in femur defects of ovariectomized rats, followed by sequential fluorochrome labeling and histological staining., Results: Compared to Ti, the Ta substrates demonstrated higher viable cell percentages (96.5 ± 0.26 vs. 88.17 ± 2.23%), lower ROS levels (65% vs. Ti), and enhanced ALP activity and extracellular matrix calcification. Reverse Transcription-Polymerase Chain Reaction and Western blot assays validated the better osteoinductive effect of Ta regarding small mothers against decapentaplegic homologs 1 (Smad1), runt-related transcription factor 2, bone morphogenetic protein (BMP2), and ALP expression at both the mRNA (1.5-2-fold) and protein (1.2-1.8-fold) levels. BMP2/Smad1 signaling over-expression or knockdown yielded significantly enhanced or deteriorated OVX-rBMSC osteogenesis on the two surfaces. In addition, the Ta group revealed more new bone formation (1.3-1.5-fold vs. Ti) and slightly better bone-implant contact (31.82 ± 4.07 vs. 25.2-3.84% at 8 weeks post-implantation, p = 0.052) without the contribution of specific surface structures., Conclusions: In comparison to Ti, Ta reveals better biocompatibility and osteoinductivity to OVX-rBMSCs, and the preferential Ta osteoinductivity may reflect its greater potential to trigger the BMP2/Smad1 cascade. Thus," in front of "Ta". Ta appears preferable to Ti as a bone-implant surface material under osteoporosis conditions.

Aim: To investigate the utility of renal diffusion tensor imaging (DTI) to detect early renal damage in patients with type 2 diabetes., Methods: Twenty-six diabetic patients (12 with microalbuminuria (MAU), and 14 with normoalbuminuria) and fourteen healthy volunteers were prospectively included in this study. Renal DTI on 3.0 T MR was performed, and estimated glomerular filtration rate (eGFR) was recorded for each subject. Mean cortical and medullary fractional anisotropy (FA) values were calculated by placing multiple representative regions of interest. Mean FA values were statistically compared among groups. Correlations between FA values and eGFR were evaluated., Results: Both cortical and medullary FA were significantly reduced in diabetic patients compared to healthy controls (0.403 ± 0.064 vs 0.463 ± 0.047, P = 0.004, and 0.556 ± 0.084 vs 0.645 ± 0.076, P = 0.002, respectively). Cortical FA was significantly lower in diabetic patients with NAU than healthy controls (0.412 ± 0.068 vs 0.463 ± 0.047, P = 0.02). Medullary FA in diabetic patients with NAU and healthy controls were similar (0.582 ± 0.096 vs 0.645 ± 0.076, P = 0.06). Both cortical FA and medullary FA correlated with eGFR ( r = 0.382, P = 0.015 and r = 0.552, P = 0.000, respectively)., Conclusion: FA of renal parenchyma on DTI might serve as a more sensitive biomarker of early diabetic nephropathy than MAU., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interests.

The purpose of this study was to evaluate the roles of different housing environments in neurological function, cerebral metabolism, cerebral infarction and neuron apoptosis after focal cerebral ischemia. Twenty-eight Sprague-Dawley rats were divided into control group (CG) and cerebral ischemia group, and the latter was further divided into subgroups of different housing conditions: standard environment (SE) subgroup, individual living environment (IE) subgroup, and enriched environment (EE) subgroup. Focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO). Beam walking test was used to quantify the changes of overall motor function. Cerebral infarction and cerebral metabolism were studied by in vivo magnetic resonance imaging and 1 H-magnetic resonance spectra, respectively. Neuron necrosis and apoptosis were detected by hematoxylin-eosin and TUNEL staining methods, respectively. The results showed that performance on the beam-walk test was improved in EE subgroup when compared to SE subgroup and IE subgroup. Cerebral infarct volume in IE subgroup was significantly larger than that in SE subgroup (P<0.05) and EE subgroup (P<0.05) on day 14 after MCAO. NAA/Cr and Cho/Cr ratios were lower in MCAO groups under different housing conditions as compared to those in CG (P<0.05). NAA/Cr ratio was lower in IE subgroup (P<0.05) and higher in EE subgroup (P<0.05) than that in SE subgroup. NAA/ Cr ratio in EE was significantly higher than that in IE subgroup (P<0.05). Cho/Cr ratio was decreased in MCAO groups as compared to that in CG (P<0.05). A significant decrease in normal neurons in cerebral cortex was observed in MCAO groups as compared to CG (P<0.05). The amount of normal neurons was less in IE subgroup (P<0.05), and more in EE subgroup (P<0.05) than that in SE subgroup after MCAO. The amount of normal neurons in EE subgroup was significantly more than that in IE subgroup after MCAO (P<0.05). The ratio of TUNEL-positive neurons in EE was significantly lower than that in SE subgroup (P<0.05) and IE subgroup (P<0.05). Correlation analysis showed that the beam walking test was negatively correlated with NAA/Cr ratio (P<0.05). Cerebral infarct volume was negatively correlated with both NAA/Cr ratio (P<0.01) and Cho/Cr ratio (P<0.01). The amount of normal cortical neurons was positively correlated with both NAA/Cr ratio (P<0.01) and Cho/Cr ratio (P<0.05). The TUNEL-positive neurons showed a negative correlation with both NAA/Cr ratio (P<0.01) and Cho/Cr ratio (P<0.01). This study goes further to show that EE may improve neurological functional deficit and cerebral metabolism, decrease cerebral infarct volume, neuron necrosis and apoptosis, while IE may aggravate brain damage after MCAO.

A magnetic metal organic framework (MMOF) was synthesized and used to separate Sr2+ in aqueous solution. The shape and structure of prepared Fe3O4@UiO-66-NH2 were characterized, and the absorbed concentration of strontium was determined through inductively coupled plasma mass spectrometry. The results indicated that Fe3O4 and UiO-66-NH2 combined through chemical bonding. The experimental adsorption results for separation of Sr2+ in aqueous solution indicated that the adsorption of Sr2+ to Fe3O4@UiO-66-NH2 increased drastically from pH 11 to pH 13. The adsorption isotherm model indicated that the adsorption of Sr2+ conformed to the Freundlich isotherm model (R2 = 0.9919). The MMOF thus inherited the superior qualities of magnetic composites and metal organic frameworks, and can easily be separated under an external magnetic field. This MMOF thus has potential applications as a magnetic adsorbent for low level radionuclide 90Sr., (Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Lenalidomide is an immunomodulatory drug and possesses anti-angiogenic and immunomodulatory activities against multiple myeloma. The present study assessed the in vitro effect of lenalidomide combined with cisplatin on MDA-MB-231, a triple-negative breast cancer (TNBC) cell line and explored the underlying molecular mechanism of this combination. Cell viability, apoptosis and the protein expression of phosphorylated (p) and total extracellular signal-regulated kinase (ERK), B-cell lymphoma-2 (Bcl-2), caspase-3, cleaved poly-adenosine diphosphate-ribose polymerase (cPARP), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were measured in MDA-MB-231 cells treated with different concentrations of lenalidomide, cisplatin and their combination using different biochemical assays. Lenalidomide demonstrated no significant effect on the cell viability of MDA-MB-231 cells, even at high concentrations, whereas lenalidomide in combination with cisplatin, significantly reduced cisplatin IC 50 from 7.8 to 3.0 µM in MDA-MB-231 cells. In addition, lenalidomide and cisplatin in combination significantly induced cell apoptosis by 1.6- and 1.38-fold, respectively compared with lenalidomide and cisplatin alone (P<0.05). The expression levels of VEGF, bFGF and Bcl-2 proteins were significantly reduced (P<0.01), whereas caspase-3 and cleaved PARP expression were significantly increased in MDA-MB-231 cells treated with the combination compared to those treated with single agents (P<0.01). Lenalidomide treatment alone significantly reduced the p-ERK level compared with the control (P<0.05) and cisplatin treatment alone significantly increased it (P<0.01), however treatment with them in combination significantly reduced the p-ERK level in MDA-MB-231 cells compared with cisplatin treatment alone (P<0.05). In conclusion, the present study provides the basis for using lenalidomide in combination with cisplatin in TNBC therapy.

Objective: To investigate the expression of long non-coding RNA zinc-finger E-box binding homeobox 1-AS1 (lncRNA ZEB1-AS1) in gastric cancer cells and tissues, to study its effect on the gastric cancer cell metastasis capacity, and analyze its clinical significance., Patients and Methods: The relative expression level of lncRNA ZEB1-AS1 in gastric cancer cells was detected via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Transwell assay was used to detect the effects of lncRNA ZEB1-AS1 on the invasion and metastasis capacities of gastric cancer cells. qRT-PCR was used to detect the relative expression level of lncRNA ZEB1-AS1 in 75 pairs of gastric cancer tissues, and the correlations of its expression with the pathological characteristics and prognosis of patients were statistically analyzed., Results: qRT-PCR showed that compared with that in the normal gastric epithelial cell (GES-1), the expression level of lncRNA ZEB1-AS1 was up-regulated in gastric cancer cells (MKN28, MKN45, BGC823, MGC803, KATOIII, and SGC7901). LncRNA ZEB1-AS1 interfering sequence was transfected into model cells, and Transwell assay showed that the cell invasion and migration capacities were significantly inhibited. qRT-PCR also revealed that the expression of lncRNA ZEB1-AS1 was up-regulated in 55 out of 75 cases of gastric cancer and para-carcinoma tissues (fold change > 1). Statistical analysis showed that the high expression of lncRNA ZEB1-AS1 was positively correlated with TNM staging (p = 0.002), lymph node metastasis (p = 0.002), and invasion degree (p = 0.004). The survival time of patients with high expression of lncRNA ZEB1-AS1 in gastric cancer tissues was shorter than that of patients with low expression (p = 0.004)., Conclusions: LncRNA ZEB1-AS1 is highly expressed in gastric cancer tissues and cells, and it is expected to be a new prognostic marker of gastric cancer used for the clinical diagnosis and prognostic evaluation. After intervention in lncRNA ZEB1-AS1 expression, the cell invasion and migration are inhibited, and lncRNA ZEB1-AS1 may be an important target to reverse the malignant phenotype of gastric cancer.

Objective: To study the effect of rhubarb on neonatal rats with bronchopulmonary dysplasia (BPD) induced by hyperoxia., Methods: A total of 64 rats (postnatal day 4) were randomly divided into four groups: air control, rhubarb control, hyperoxia model, and hyperoxia+rhubarb (n=16 each). The rats in the hyperoxia model and hyperoxia+rhubarb groups were exposed to hyperoxia (60% O2) to establish a BPD model. The rats in the rhubarb control and hyperoxia+rhubarb groups were given rhubarb extract suspension (600 mg/kg) by gavage daily. The pathological changes of lung tissue were evaluated by hematoxylin-eosin staining on postnatal days 14 and 21. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured by spectrophotometry. The mRNA and protein expression levels of tumor necrosis factor-alpha (TNF-&alpha;) and interleukin-6 (IL-6) were determined by RT-PCR and Western blot respectively., Results: The hyperoxia model group showed reduced alveolar number, increased alveolar volume, and simplified alveolar structure, which worsened over the time of exposure to hyperoxia. These pathological changes were significantly reduced in the hyperoxia+rhubarb group. On postnatal days 14 and 21, compared with the air control and rhubarb control groups, the hyperoxia model group had significantly reduced radical alveolar count (RAC), significantly reduced activity of SOD in the lung tissue, and significantly increased content of MDA and mRNA and protein expression levels of TNF-&alpha; and IL-6 (P&lt;0.05). Compared with the hyperoxia model group, the hyperoxia+rhubarb group had significantly increased RAC, significantly increased activity of SOD in the lung tissue, and significantly reduced content of MDA and mRNA and protein expression levels of TNF-&alpha; and IL-6 (P&lt;0.05)., Conclusions: Rhubarb may play a protective role in rats with BPD induced by hyperoxia through inhibiting inflammatory response and oxidative stress.

A de novo designed intramolecular disulfide bond in myoglobin, resembling that in cytoglobin without structural evidence, was confirmed by an X-ray structure for the first time and was demonstrated to regulate both the structure and function of this protein, which fulfills the design of an artificial dehaloperoxidase, with an activity exceeding that of a native enzyme.

Plants generate reactive oxygen species (ROS) in the apoplast in response to pathogen attack, especially following resistance ( R ) gene-mediated pathogen recognition; however, the mechanisms activating ROS generation remain unknown. Here, we demonstrate that RKN ( Meloidogyne incognita ) infection rapidly induces ROS accumulation in the roots of tomato ( Solanum lycopersicum ) plants that contain the R gene Mi-1.2 but rarely induces ROS accumulation in the susceptible or Mi-1.2 -silenced resistant genotypes. RNK also induces the hypersensitive response, a form of programmed cell death, in Mi-1.2 plants. RKN induces the expression of numerous class-A heat shock factor (HsfA) genes in resistant tomato plants. Silencing HsfA1a compromises Mi-1.2 -mediated resistance, apoplastic H 2 O 2 accumulation, and the transcription of whitefly induced 1 ( Wfi1 ), which encodes a respiratory burst oxidase homolog. HsfA1a regulates Wfi1 transcription by binding to the Wfi1 promoter, and silencing of Wfi1 compromises Mi-1.2 -mediated resistance. HsfA1a and Wfi1 are involved in Mi-1.2-triggered Hsp90 accumulation and basal defense in susceptible tomato. Thus, HsfA-1aWfi1-dependent ROS signaling functions as a crucial regulator of plant defense responses., (© 2018 American Society of Plant Biologists. All Rights Reserved.)

The catalytic degradation of 1,2-dichloroethane (DCE) at CeO 2 (111) was investigated using periodic density functional theory calculations corrected by on-site Coulomb interactions. From thorough calculations of possible elementary steps, we are able to identify the lowest energy reaction pathway for the catalytic oxidation of DCE at CeO 2 (111). It proceeds via two successive C-Cl bond breaking processes to form adsorbed CH 2 CH 2 species, and after further dehydrogenation and C-C bond scission, the surface species are finally oxidized to CO 2 and H 2 O. The surface oxygen vacancies were found to be important for the catalytic decomposition of DCE, by providing the adsorption sites, as well as for charge transfer to favor C-Cl bond breaking. We are also able to illustrate the effect of H 2 O on the catalytic activity of CeO 2 (111) for DCE oxidation.

Purpose: To determine whether gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict presence of lymphovascular invasion and T-stages., Results: Gross tumor volume increased with the lymphovascular invasion ( r = 0.426, P < 0.0001) and T stage ( r = 0.656, P < 0.0001). Univariate analysis showed gross tumor volume could predict lymphovascular invasion ( P < 0.0001). Multivariate analyses indicated gross tumor volume as an independent risk factor of lymphovascular invasion ( P = 0.026, odds ratio = 2.284). The Mann-Whitney U test showed gross tumor volume could distinguish T2 from T3, T1 from T2-T4a, T1-T2 from T3-T4a and T1-T3 from T4a ( P = 0.000). In the development cohort, gross tumor volume could predict lymphovascular invasion (cutoff, 15.92 cm 3 ; AUC, 0.760), and distinguish T2 from T3 (cutoff, 10.09 cm 3 ; AUC, 0.828), T1 from T2-T4a (cutoff, 8.20 cm 3 ; AUC, 0.860), T1-T2 from T3-T4a (cutoff, 15.88 cm 3 ; AUC, 0.883), and T1-T3 from T4a (cutoff, 21.53 cm 3 ; AUC, 0.834). In validation cohort, gross tumor volume could predict presence of lymphovascular invasion (AUC, 0.742), and distinguish T2 from T3 (AUC, 0.861), T1 from T2-T4a (AUC, 0.859), T1-T2 from T3-T4a (AUC, 0.875), and T1-T3 from T4a (AUC, 0.773)., Materials and Methods: 360 consecutive patients with gastric adenocarcinoma were retrospectively identified. Gross tumor volume was evaluated on multidetector computed tomography images. Statistical analysis was performed to determine whether gross tumor volume could predict presence of lymphovascular invasion and T-stages. Cutoffs of gross tumor volume were first investigated in 212 patients and then validated in an independent 148 patients using area under the receiver operating characteristic curve (AUC) for predicting lymphovascular invasion and T-stages., Conclusions: Gross tumor volume of resectable gastric adenocarcinoma at multidetector computed tomography demonstrated capability in predicting lymphovascular invasion and distinguishing T-stages., Competing Interests: CONFLICTS OF INTEREST All authors stated that there were no conflicts of interest in this study.

To compare the ability of CT angiography (CTA) obstruction score and perfusion defect score on dual energy CT perfusion imaging (DEPI) for clinical risk stratification of patients with acute pulmonary embolism (PE). 55 patients diagnosed as acute PE either by CTA or DEPI were retrospectively enrolled. Patients were grouped into high-, intermediate-, and low-risk groups in accordance to the renewed guidelines of 2014. Consistency between DEPI and CTA in diagnosis of PE were assessed. Correlations between CT parameters and right-to-left ventricular (RV/LV) diameter ratio were evaluated. Difference of CTA obstruction score and perfusion defect score across three groups with different risks were analyzed. The consistent rate of DEPI with CTA was 75.4%, and the Kappa value was 0.412 (p = 0.000). 44.3% of partially obstructive PE showed on CTA did not lead to perfusion defect on DEPI. Perfusion defect score was significantly correlated with CTA obstruction score and with RV/LV (r = 0.622 and 0.599, respectively, p < 0.001), and CTA obstruction score had lower correlation with RV/LV (r = 0.403, p = 0.003). Perfusion defect score could distinguish low- from intermediate-risk groups (p = 0.011). However, CTA obstruction score could not distinguish the two groups (p = 0.149). DEPI had fine consistency with CTA to diagnose acute PE and offered additional information of physiologic changes. Comparing with CTA obstruction score, perfusion defect score could better correlate with right ventricular dysfunction, and could be a more promising biomarker for clinical risk stratification.

Objective: To investigate the relationship between the gene polymorphism of osteoprotegerin (OPG) and bone mineral density (BMD) in hemodialysis patients., Patients and Methods: A total of 147 patients with end-stage renal disease (ESRD) who were admitted to the Weifang People's Hospital for maintenance hemodialysis between January 2014 and December 2015 were enrolled. Peripheral blood was collected from the subjects for assay of the polymorphism of A163G and G1181C loci of OPG. The measurements of the levels of RANK, RANKL, TNF-α, IL-6, PINP, CTX-I, CTX-II and TRACP5 in the isolated serum were taken., Results: For the polymorphism of A163G locus on the OPG gene, the BMDs of left femoral neck and lumbar poster anterior L1-L4 of the AA genotype were significantly higher than those of the AG and GG genotypes. There was no significant difference in comparison of BMDs at the forearm (distal 1/3) between the AA genotype and AG and GG genotypes. No significant differences were found in the comparison of BMDs at all sites between AG and GG genotypes. The serum level of RANKL of the AA genotype was significantly higher than levels of AG and GG genotypes, but the levels of RANK, TNF-α, IL-6, PINP, CTX-I, CTX-II and TRACP5 were prominently lower than those levels of AG and GG genotypes. For the polymorphism of G1181C locus on the OPG gene, the BMDs of left femoral neck and lumbar poster anterior L1-L4 of the CC genotype were significantly higher than the BMDs of GG and GC genotypes, There was no significant difference in the comparison of BMDs at the forearm (distal 1/3) between the CC genotype and GG and GC genotypes. No significant differences were found in the comparison of BMDs at all sites between GG and GC genotypes. The serum level of RANKL of the CC genotype was significantly higher than the level of GG and GC genotypes. However, the levels of RANK, TNF-α, IL-6, PINP, CTX-I, CTX-II and TRACP5 were prominently lower than those levels of GG and GC genotypes., Conclusions: The polymorphisms of A163G and G1181C loci on the OPG gene were correlated with the BMD of hemodialysis patients. The genotype AA of A163G and genotype CC of G1181C were identified as the protective factors for BMD.

MicroRNAs (miRNAs) are small noncoding RNAs, which regulate numerous cell functions by targeting mRNA for cleavage or translational repression, and have been found to play an important role in Alzheimer's disease (AD). Our study aimed to identify differentially expressed miRNAs in AD brain as a reference of potential therapeutic miRNAs or biomarkers for this disease. We used amyloid precursor protein (APP) and presenilin 1 (PS1) double transgenic mice and age-matched wild-type (WT) littermates to determine the expression of miRNAs in the brain. MiRNAs were profiled by microarray, and differentially expressed miRNAs underwent target prediction and enrichment analysis. Microarray analysis revealed 56 differentially expressed miRNAs in AD mouse brain, which involved 39 miRNAs that were significantly upregulated and 19 that were downregulated at different ages. Among those miRNAs, a total of 11 miRNAs, including miR-342-3p, miR-342-5p, miR-376c-3p, and miR-301b-3p, were not only conserved in human but also predicted to have targets and signaling pathways closely related to the pathology of AD. In conclusion, in this study, differentially expressed miRNAs were identified in AD brain and proposed as biomarkers, which may have the potential to indicate AD progression. Despite being preliminary, these results may aid in investigating pathological hallmarks and identify effective therapeutic targets.

Objective: Although diffusion-weighted magnetic resonance imaging (DWI) has been widely used in the diagnosis of cervical cancer, whether it can predict disease recurrence or survival remains inconclusive. This study aimed to systematically evaluate whether DWI can serve as a reliable prognostic predictor in patients with cervical cancer., Methods: PubMed, the MEDLINE database and the Cochrane Library were searched for DWI studies with >12 months of prognostic data in patients with cervical cancer. Endpoints included tumor recurrence and death. Methodological quality was assessed using the Quality in Prognostic Studies (QUIPS) tool. Combined estimates of hazard ratios (HRs) were derived., Results: Nine studies involving a total of 796 patients (mean/median age from 45.0 years to 62.9 years) met the inclusion criteria. Methodological quality was relatively high. Eight of the nine studies employed apparent diffusion coefficient (ADC) as an indicator of DWI results. Using disease-free survival (DFS) as an outcome measure, nine studies yielded a combined HR of 1.55 (95% confidence interval (CI): 1.23-1.95), and seven studies that employed pretreatment DWI yielded a combined HR of 1.50 (95% CI: 1.03-2.19), which indicated that unfavorable DWI results were associated with an approximately 1.50-1.55-fold higher risk of tumor recurrence. The two studies investigating the impact of DWI results on overall survival (OS) reported HRs of 7.20 and 2.17, respectively., Conclusion: DWI may serve as a predictor of tumor recurrence in patients with cervical cancer as showed by meta-analysis, and the quantified ADC as a suitable candidate indicator., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Acoustic illusion cloaks that create illusion effects by changing the scattered wave have many potential applications in a variety of scenarios. However, the experimental realization of generating three-dimensional (3D) acoustic illusions under detection of broadband signals still remains challenging despite the paramount importance for practical applications. Here we report the design and experimental demonstration of a 3D broadband cloak that can effectively manipulate the scattered field to generate the desired illusion effect near curved boundaries. The designed cloak simply comprises positive-index anisotropic materials, with parameters completely independent of either the cloaked object or the boundary. With the ability of manipulating the scattered field in 3D space and flexibility of applying to arbitrary geometries, our method may take a major step toward the real world application of acoustic cloaks and offer the possibilities of building advanced acoustic devices with versatile functionalities.

We theoretically design and numerically demonstrate an acoustic one-way metasurface, which is a planar and acoustically subwavelength layer behaving like a nearly-reflectionless surface with arbitrary wave-steering capability for incident wave impinging on one side, while virtually blocking the reversed wave. The underlying mechanism is based on an asymmetric phase modulation by coupling a phase array and a near-zero-index medium. We exemplify a metastructure-based implementation by combining the hybrid metastuctures and labyrinthine structures. Moreover, the performance of the proposed implementation is demonstrated via three distinct phenomena of anomalous refraction, wave splitting and conversion of propagation wave to surface wave. Our findings may offer more possibilities for sound manipulation and improve the application potential of acoustic artificial devices in situations such as ultrasonic imaging and therapy.

Objective: To study the relationship between the component content of curcuminoids in Curcumae Longae Rhizoma and powder color indeces L*, a* and b* those were measured by chromaticity instrument, in order to provide scientific basis for quality assessment of Curcuma longa medicinal materials., Methods: Detect the content of curcumin,demethoxycurcumin,bisdemethoxycurcumin,then detect the content of curcuminoids by the Chinese Pharmacopoeia method. Measure the color indeces L*, a* and b* of Curcumae Longae Rhizoma powder by colorimeter. Finally, the relationship between the content and the color was analyzed by using the Grey Relational Analysis, Pearson correlation coefficient and regression analysis., Results: There was positive correlation between the content of curcuminoids and a*. But there was no definitely relation between the content of curcuminoids and b* or L*., Conclusion: The content of curcuminoids is closely related with the degree of the color red, the higher the content, the red is deeper. a* could be recognized as an important basis of Curcumae Longae Rhizoma medicinal materials quality.

The plant hormone auxin is perceived by the nuclear F-box protein TIR1 receptor family and regulates gene expression through degradation of Aux/IAA transcriptional repressors. Several studies have revealed the importance of the proteasome in auxin signalling, but details on how the proteolytic machinery is regulated and how this relates to degradation of Aux/IAA proteins remains unclear. Here we show that an Arabidopsis homologue of the proteasome inhibitor PI31, which we name PROTEASOME REGULATOR1 (PTRE1), is a positive regulator of the 26S proteasome. Loss-of-function ptre1 mutants are insensitive to auxin-mediated suppression of proteasome activity, show diminished auxin-induced degradation of Aux/IAA proteins and display auxin-related phenotypes. We found that auxin alters the subcellular localization of PTRE1, suggesting this may be part of the mechanism by which it reduces proteasome activity. Based on these results, we propose that auxin regulates proteasome activity via PTRE1 to fine-tune the homoeostasis of Aux/IAA repressor proteins thus modifying auxin activity.

Objective: To determine whether the gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict the presence of regional lymph node metastasis and could determine N categories., Materials and Methods: A total of 202 consecutive patients with gastric adenocarcinoma who had undergone gastrectomy 1 week after contrast-enhanced multidetector computed tomography were retrospectively identified. The gross tumor volume was evaluated on multidetector computed tomography images. Univariate and multivariate analyses were performed to determine whether the gross tumor volume could predict regional lymph node metastasis, and the Mann-Whitney U test was performed to compare the gross tumor volume among N categories. Additionally, a receiver operating characteristic analysis was performed to identify the accuracy of the gross tumor volume in differentiating N categories., Results: The gross tumor volume could predict regional lymph node metastasis (p<0.0001) in the univariate analysis, and the multivariate analyses indicated that the gross tumor volume was an independent risk factor for regional lymph node metastasis (p=0.005, odds ratio=1.364). The Mann-Whitney U test showed that the gross tumor volume could distinguish N0 from the N1-N3 categories, N0-N1 from N2-N3, and N0-N2 from N3 (all p<0.0001). In the T1-T4a categories, the gross tumor volume could differentiate N0 from the N1-N3 categories (cutoff, 12.3 cm3), N0-N1 from N2-N3 (cutoff, 16.6 cm3), and N0-N2 from N3 (cutoff, 24.6 cm3). In the T4a category, the gross tumor volume could differentiate N0 from the N1-N3 categories (cutoff, 15.8 cm3), N0-N1 from N2-N3 (cutoff, 17.8 cm3), and N0-N2 from N3 (cutoff, 24 cm3)., Conclusion: The gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict regional lymph node metastasis and N categories.

2-Cys peroxiredoxins (2-CPs) function in the removal of hydrogen peroxide and lipid peroxides but their precise roles in the induction of autophagy have not been characterized. Here we show that heat stress, which is known to induce oxidative stress, leads to the simultaneous accumulation of transcripts encoding 2-CPs and autophagy proteins, as well as autophagosomes, in tomato (Solanum lycopersicum) plants. Virus-induced gene silencing of the tomato peroxiredoxin genes 2-CP1, 2-CP2, and 2-CP1/2 resulted in an increased sensitivity of tomato plants to heat stress. Silencing 2-CP2 or 2-CP1/2 increased the levels of transcripts associated with ascorbate biosynthesis but had no effect on the glutathione pool in the absence of stress. However, the heat-induced accumulation of transcripts associated with the water-water cycle was compromised by the loss of 2-CP1/2 functions. The transcript levels of autophagy-related genes ATG5 and ATG7 were higher in plants with impaired 2-CP1/2 functions, and the formation of autophagosomes increased, together with an accumulation of oxidized and insoluble proteins. Silencing of ATG5 or ATG7 increased the levels of 2-CP transcripts and protein but decreased heat stress tolerance. These results demonstrate that 2-CPs fulfil a pivotal role in heat stress tolerance in tomato, via interactions with ascorbate-dependent pathways and autophagy., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Brassinosteroids (BRs) play a critical role in plant growth, development and stress response; however, genetic evidence for the BR-mediated integrated regulation of plant growth still remains elusive in crop species. Here, we clarified the function of DWARF (DWF), the key BR biosynthetic gene in tomato, in the regulation of plant growth and architecture, phytohormone homeostasis and fruit development by comparing wild type, d^(im), a weak allele mutant impaired in DWF, and DWF-overexpressing plants in tomato. Results showed that increases in DWF transcripts and endogenous BR level resulted in improved germination, lateral root development, CO2 assimilation and eventually plant growth as characterized by slender and compact plant architecture. However, an increase in DWF transcript down-regulated the accumulation of gibberellin, which was associated with decreases in leaf size and thickness. BRs positively regulated lateral bud outgrowth, which was associated with decreased transcript of Aux/IAA3, and the ethylene-dependent petiole bending and fruit ripening. Notably, overexpression of DWF did not significantly alter fruit yield per plant; however, increases by 57.4% and 95.3% might be estimated in fruit yield per square metre in two transgenic lines due to their compact architecture. Significantly, BR level was positively related with the carotenoid accumulation in the fruits. Taken together, our results demonstrate that BRs are actively involved in the regulation of multiple developmental processes relating to agronomical important traits., (© 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.)

Objective: To observe the effect of Zishen Huoxue Recipe (ZHR) on pathomorphology in coronary heart disease (CHD) rats with Shen deficiency blood stasis syndrome (SDBSS)., Methods: Totally 60 healthy Wistar rats were divided into the blank control group, the model group, high, middle, and low dose ZHR groups according to random digit table, 12 in each group. Myocardial ischemia SDBSS rat model was prepared by ligating the left anterior descending coronary artery and injecting hydrocortisone. ZHR physic liquor was administered to rats in high, middle, and low dose ZHR groups at the daily dose of 21.6, 10.8, 5.4 g/kg by gastrogavage for 7 successive days, equal volume of pure water was administered to rats in the blank control group and the model group by gastrogavage for 7 successive days. Rat heart was collected for pathomorphological observation under light microscope., Results: In the model group the heart muscle fiber was swollen and deformed with widened space, loose and dropsy tissues. Blood vessels in myocardial mesenchymal were dilated, infiltrated with more inflammatory cells. Myocardial cells were markedly swollen, degenerated, or necrotic, with caryolysis or disappearance of partial nuclear. A large amount of collagen fibrous tissue became hyperplasia. Endocardial blood vessels were swollen and degenerated with infiltration of few inflammatory cells. Epicardium tissue and structure were destroyed and got hyperplasia. Swollen, degenerated, or necrotic vessels could be seen, with infiltration of more inflammatory cells and collagen deposition. Pathomorphological injuries were alleviated in each ZHR group. The higher ZHR concentration, the milder the injury degree of myocardial tissue, the more limited range of damage., Conclusion: ZHR could attenuate pathomorphological injuries of myocardial ischemia rats with SDBSS and regulate myocardial function, thus improving myocardial ischemia in CHD rats with SDBSS.

Characterization of protein interactions is essential to the discovery of disease biomarkers, the development of diagnostic assays, and the screening for therapeutic drugs. Conventional flow-through kinetic measurements need relative large amount of sample that is not feasible for precious protein samples. We report a novel method to measure protein interaction kinetics in a single droplet with sub microliter or less volume. A droplet in a humidity-controlled environmental chamber is replacing the microfluidic channels as the reactor for the protein interaction. The binding process is monitored by a surface plasmon resonance imaging (SPRi) system. Association curves are obtained from the average SPR image intensity in the center area of the droplet. The washing step required by conventional flow-through SPR method is eliminated in the droplet method. The association and dissociation rate constants and binding affinity of an antigen-antibody interaction are obtained by global fitting of association curves at different concentrations. The result obtained by this method is accurate as validated by conventional flow-through SPR system. This droplet-based method not only allows kinetic studies for proteins with limited supply but also opens the door for high-throughput protein interaction study in a droplet-based microarray format that enables measurement of many to many interactions on a single chip.

Kidney transplantation has emerged as the treatment of choice for many patients with end-stage renal disease, which is a significant cause of morbidity and mortality. Given the shortage of clinically available donor kidneys and the significant incidence of allograft dysfunction, a noninvasive and accurate assessment of the allograft renal function is critical for postoperative management. Prompt diagnosis of graft dysfunction facilitates clinical intervention of kidneys with salvageable function. New advances in magnetic resonance imaging (MRI) technology have enabled the calculation of various renal parameters that were previously not feasible to measure noninvasively. Diffusion-weighted imaging provides information on renal diffusion and perfusion simultaneously, with quantification by the apparent diffusion coefficient, the decrease of which reflects renal function impairment. Diffusion-tensor imaging accounts for the directionality of molecular motion and measures fractional anisotropy of the kidneys. Blood oxygen level-dependent MR evaluates intrarenal oxygen bioavailability, generating the parameter of R2* (reflecting the concentration of deoxyhemoglobin). A decrease in R2* could happen during acute rejection. MR nephro-urography/renography demonstrates structural data depicting urinary tract obstructions and functional data regarding the glomerular filtration and blood flow. MR angiography details the transplant vasculature and is particularly suitable for detecting vascular complications, with good correlation with digital subtraction angiography. Other functional MRI technologies, such as arterial spin labeling and MR spectroscopy, are showing additional promise. This review highlights MRI as a comprehensive modality to diagnose a variety of etiologies of graft dysfunction, including prerenal (e.g., renal vasculature), renal (intrinsic causes) and postrenal (e.g., obstruction of the collecting system) etiologies.

Objective: To clone the variable region genes of human anti-IL1RAP (IL-1 receptor accessory protein) monoclonal antibodies (McAb) and to construct IL1RAP chimeric antigen receptors (CARs)., Methods: The VH and VL DNA of IL1RAP single chain antibodies were amplified by RACE and overlap extension PCR from total RNA extracted from 3H6E10 and 10D8A7 hybridoma and ligated into specific IL1RAP single-chain variable fragments (scFv). CD8α transmembrane domain, CD137 intracellular domain, TCR ζ chain, human CD8α signal peptide and scFv-anti-IL1RAP were cloned into plasmid LV-lac. Recombinant lentiviruses were generated by co-transfection of recombinant plasmid LV-lac, pMD2. G, and psPAX2 helper vectors into 293FT packing cells., Results: The VH and VL genes of 2 human anti-IL1RAP McAb were acquired. The 3H6E10 VH and VL genes consisted of 402 bp and 393 bp encoding 134 and 131 aminoacid residues, respectively; 10D8A7 VH and VL genes consisted of 423 bp and 381 bp encoding 141 and 127 amine acid residues, respectively. Recombinant expression vertors LV-3H6E10 scFv-ICD and LV-10D8A7 scFv-ICD (ICD: CD8α transmembrane domain-CD137 intracellular domain-TCR ζ chain) were constructed. The target fragments were demonstrated by sequencing analysis. Recombinant plasmids were transfected into 293FT cells and lentiviral particles were acquired., Conclusion: Human anti-IL1RAP recombinant receptors are constructed successfully and lay a good foundation for the construction of IL1RAP-CAR killer T cell vaccine.

Objective: To prepare and identify human monoclonal antibody against IL-1 receptor accessory protein (IL1RAP), which is a new identified surface marker for leukemia stem cells (LSC)., Methods: BALB/c mice were inoculated intraperitoneally with hybridoma cells (3H6E10, 10D8A7) and their ascites were collected. The monoclonal antibody against hu-IL1RAP specifically was purified from ascites, the nondenaturing-PAGE, ELISA and Western blot were used to detect the purity, titer and sensitivity of antibody., Results: Two purified antibodies were obtained and named as 3H6E10 McAb and 10D8A7 McAb, whose purity was 95% and 94% respectively. The titer of two purified monoclonal antibodies was 1 : 81000 and specific conjugation of IL1RAP purified protein and endogenous protein from normal people and leukemia patients with purified antibodies were confirmed., Conclusion: The purified monoclonal antibodies which can specifically bind to hu-IL1RAP are successfully prepared, thus providing novel way to effectively clear LSC in the future.