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The genetic events occurring in recurrent nasopharyngeal carcinoma (rNPC) are poorly understood. Here, we performed whole-genome and whole-exome sequencing in 55 patients with rNPC and 44 primarily diagnosed NPC (pNPC), with 7 patients having paired rNPC and pNPC samples. Previously published pNPC exome data were integrated for analysis. rNPC and pNPC tissues had similar mutational burdens, however, the number of clonal mutations was increased in rNPC samples. TP53 and three NF-κB pathway components (TRAF3, CYLD, and NFKBIA) were significantly mutated in both pNPC and rNPC. Notably, mutations in TRAF3, CYLD, and NFKBIA were all clonal in rNPC, however, 55.6% to 57.9% of them were clonal in pNPC. In general, the number of clonal mutations in NF-κB pathway–associated genes was significantly higher in rNPC than in pNPC. The NF-κB mutational clonality was selected and/or enriched during NPC recurrence. The amount of NF-κB translocated to the nucleus in samples with clonal NF-κB mutants was significantly higher than that in samples with subclonal NF-κB mutants. Moreover, the nuclear abundance of NF-κB protein was significantly greater in pNPC samples with locoregional relapse than in those without relapse. Furthermore, high nuclear NF-κB levels were an independent negative prognostic marker for locoregional relapse-free survival in pNPC. Finally, inhibition of NF-κB enhanced both radiosensitivity and chemosensitivity in vitro and in vivo. In conclusion, NF-κB pathway activation by clonal mutations plays an important role in promoting the recurrence of NPC. Moreover, nuclear accumulation of NF-κB is a prominent biomarker for predicting locoregional relapse-free survival. Significance: This study uncovers genetic events that promote the progression and recurrence of nasopharyngeal carcinoma and has potential prognostic and therapeutic implications. See related commentary by Sehgal and Barbie, p. 5915

This study focuses on the impact-sliding wear behaviour of CrN and WC/C tool protection coatings against Si3N4 ceramic material using a self-developed impact-sliding device. The wear mechanisms and...

OBJECTIVE The aim of this study was to compare stage II/III rectal cancers with or without high-risk factors, and evaluate the effect of neoadjuvant radiotherapy (NRT) in these 2 cohorts. BACKGROUND NRT is often used in stage II/III rectal cancers to improve local control, while not affecting overall survival. However, good-quality surgery without NRT may also achieve good local control in selected patients. METHODS According to risk-stratification criteria and clinical staging, consecutive eligible participants of stage II/III rectal cancer were preoperatively classified into patients with (high-risk) or without (low-risk) high-risk factors. Both groups were respectively randomized to receive either short-course radiotherapy (SCRT) + total mesorectal excision (TME) or TME alone, forming the following 4 groups: high-risk patients with (HiR) or without (HiS) radiation, and low-risk patients with (LoR) or without (LoS) radiation. The primary endpoint was local recurrence. The secondary endpoints included overall survival, disease-free survival, distant recurrence, quality of surgery, and safety (NCT01437514). RESULTS In total, 401 patients were analyzed. With a median 54 months' follow-up, low-risk patients obtained better 3-year cumulative incidence of local recurrence (2.2% vs 11.0%, P = 0.006), overall survival rate (86.9%vs 76.5%, P = 0.002), disease-free survival rate (87.0% vs 67.9%, P < 0.001), and cumulative incidence of distant recurrence (12.5% vs 29.4%, P < 0.001) than high-risk patients. With regard to 3-year cumulative incidence of local recurrence, no differences were observed between the LoR and LoS groups (1.2% vs 3.0%, P = 0.983) or the HiR and HiS groups (12.9% vs 8.9%, P = 0.483). CONCLUSIONS AND RELEVANCE Stratification of stage II/III rectal cancers according to risk factors to more precise subclassifications may result in noteworthy differences in survivals and local pelvic control. An extremely low cumulative incidence of local recurrence and survivals in low-risk patients can be achieved with upfront good quality of surgery alone. This trial, owing to the insufficient power, could not prove the noninferiority of surgery alone, but suggest a discriminative use of NRT according to clinical risk stratification in stage II/III rectal cancer.

Inhomogeneity within tumors can reflect tumor angiogenesis. Existing research into the quantization of angiogenesis mainly focuses on time-intensity curve parameters but has produced inconsistent results. In clinical work, it is difficult to achieve standardization and consistency for manual judgement of the inhomogeneity of contrast-enhanced images, while the artificial intelligence technology may be helpful. The aim of this study was to assess whether computers can assist in the artificial classification of tumor inhomogeneity in contrast-enhanced ultrasound (CEUS) images of rectal cancer.A total of 500 contrast-enhanced ultrasonograms were retrospectively collected, which was verified of rectal cancer pathologically from 2016 to 2018 as training set. All images are from 18-80 years old patients with rectal cancer in our hospital. These tumors are usually located in the middle and lower segment of the rectum, which can be completely observed on ultrasound. The images were divided into 3 categories according to the inhomogeneous distribution of contrast agents inside the tumors. Computing methods were used to simulate manual classification. Computer processing steps included segmentation, gray level quantization, dimension reduction, and classification. The results of 6 different gray level quantization, 2 dimensionality reduction methods, and 3 classifiers were compared, from which the optimal parameters were selected in each step. The performance of computer classification was evaluated using manual classification results as the reference. Ninety-seven ultrasonograms of contrast-enhanced rectal tumors were collected as validation set from 2018.1 to 2018.6.The optimal gray level was set at 32. Principal component analysis (PCA) was the first choice for dimensionality reduction. The best classifier was support vector machines (SVM). The accuracy of computer classification was 87.80% (439/500). The accuracy of computer classification in the validation cohort was 60.82%. The area under the curve (AUC) of class 1, 2, and 3 were 0.76, 0.41, and 0.48, respectively.Results showed that the computer methods are competent for classifying inhomogeneity of contrast-enhanced rectal cancers inside ultrasonograms.

Background This study explored the application effect of information technology in optimizing the patient identification process. Methods The method for optimizing the identification process involved in drawing blood among outpatients using information technology was executed from July 2020. In this paper, 959 patients who had blood drawn from January to June 2020 were included as the pre-optimization group, and 1011 patients who had blood drawn from July to December 2019 were included as the post-optimization group. The correct rate of patient identification, waiting time, and patient satisfaction before and after the optimization were statistically analyzed. The changes in these three indexes before and after the optimization implementation, as well as the application effects, were compared. Results The correct rate of patient identification after optimization (99.80%) was higher than before optimization (98.02%) (X2 = 13.120; P P 2 = 20.973; P Conclusions By combining information technology with the characteristics of blood collection in our hospital, using the call system to obtain patient information, then scan the QR code of the guide sheet for automatic verification, and finally manually reconfirm patient information, which can significantly reduce the occurrence of identification errors, improve work efficiency and improve patients' satisfaction.

Hydroxygenkwanin (HGK) has an anticancer effect in a variety of tumors, but its role in osteosarcoma has not been explored. The purpose of the present study was to investigate the therapeutic effect of HGK on osteosarcoma and its specific molecular mechanism. Osteosarcoma cells (MG‑63 and U2OS) treated with various concentrations of HGK were assigned to the treatment group. MTT, clone formation, wound healing and Transwell assays were performed to assess the viability, proliferation, migration, and invasion of MG‑63 and U2OS cells. RT‑qPCR was conducted to quantify the expression levels of of microRNA (miR)‑320a and SRY‑box transcription factor 9 (SOX9) in MG‑63 and U2OS cells. The binding sites of miR‑320a and SOX9 were predicted by starBase database, and verified using the dual‑luciferase reporter assay. The expression levels of SOX9 and EMT‑related proteins (N‑cadherin, E‑cadherin and vimentin) were detected by western blot analysis. HGK inhibited cell proliferation, migration, invasion, but promoted the expression of miR‑320a in MG‑63 and U2OS cells. Downregulation of miR‑320a reversed the effects of HGK on proliferation, migration and invasion of MG‑63 and U2OS cells, while upregulation of miR‑320a had the opposite effect. HGK inhibited the expression of SOX9 by promoting the expression of miR‑320a. Upregulation of SOX9 could partially reverse miR‑320a‑induced migration and invasion of MG‑63 and U2OS cells. In addition, upregulation of miR‑320a promoted E‑cadherin expression and inhibited the expression of N‑cadherin and vimentin, and the effect of miR‑320a was also reversed by SOX9. In conclusion, HGK inhibited proliferation, migration and invasion of MG‑63 and U2OS cells through the miR‑320a/SOX9 axis.

Background Anorectal malignant melanoma (ARMM) and low rectal adenocarcinoma (LRAC) have some similarities in clinical behaviors, histopathological characteristics and ultrasonographic findings, diagnostic errors are common. By comparing the transrectally ultrasonographic features between the two tumors, we propose to provide more possibilities in differentiating them. Methods The data of 9 ARMMs and 27 age- and gender-matched LRACs (the lower margin below the peritoneal reflection) in West China Hospital Sichuan University between April 2008 and July 2019 were retrospectively reviewed. The ultrasonic features between the two groups were compared. Results Transrectal ultrasonography (TRUS) showed that the length of ARMM was shorter than that of LRAC (28.22 ± 12.29 mm vs. 40.22 ± 15.16 mm), and ARMM had a lower position than that of LRAC (the distance to anal verge was 50.78 ± 11.70 vs. 63.81 ± 18.73 mm). Unlike LRAC, the majority of ARMM in our study was confined to the intestinal mucosa/submucosa (66.67/25.93%) (P Conclusions Based on the data of our study, several ultrasonographic findings (length, invasion depth, and position) of ARMM were significantly different from LRAC. Accordingly, more attention should be paid to masses at anorectal junction with lower position, shorter length, and shallower infiltration depth. Instead of the most common tumor, LRAC, ARMM should be taken into account to avoid a misdiagnosis, which will result in a poorer prognosis.

Purpose: The present study aimed to investigate the inhibitory effect of fluorofenidone against transforming growth factor β2-induced proliferation and epithelial-mesenchymal transition in human lens epithelial cell line FHL 124 and its potential mechanism. Methods: We evaluated the effect of fluorofenidone on proliferation and epithelial-mesenchymal transition of human lens epithelial cell line FHL 124 in vitro. After treatment with 0, 0.1, 0.2, 0.4, 0.6, and 1.0 mg/mL fluorofenidone, cell proliferation was measured via MTT assay. Cell viability was evaluated by lactate dehydrogenase activity from damaged cells. FHL 124 cells were treated with different transforming growth factor β2 concentrations (0-10 ng/mL) for 24 h and the expression of CTGF, α-SMA, COL-I, E-cadherin, and Fn were detected via quantitative polymerase chain reaction and Western blot analysis. After treatment with 0, 0.2, and 0.4 mg/ml fluorofenidone, the expressions of transforming growth factor β2 and SMADs were detected with real-time polymerase chain reaction and Western blot analysis. Expressions of CTGF, α-SMA, COL-I, and Fn were analyzed by immunocytochemistry assay. Results: The viability of FHL 124 cells was not inhibited when the fluorofenidone concentration was ≤0.4 mg/mL after the 24h treatment. Cytotoxicity was not detected via lactate dehydrogenase assay after the 24h and 36h treatment with 0.2 and 0.4 mg/mL fluorofenidone. Transforming growth factor β2 increased mRNA and protein expression of CTGF, α-SMA, COL-I, and Fn. However, fluorofenidone significantly suppressed expression of SMADs, CTGF, α-SMA, COL-I, and Fn in the absence or presence of transforming growth factor β2 stimulation. Conclusions: Fluorofenidone significantly inhibited expression of SMADs, CTGF, α-SMA, COL-I, and Fn in FHL 124 cells. Due to noncompliance in infants, fluorofenidone may become a novel therapeutic drug against posterior capsular opacification in infants.

OBJECTIVE To compare the performances among three different systems for video head impulse test (vHIT), and to identify an optimal target angle for precisely evaluating the function of vertical semicircular canals in vHIT. METHODS A two-center prospective study was done. Participants were sit 1.2 m away from the wall in a noise-proved room that dedicated for vHIT experiments. During the comparison experiments, similar settings were ensured in both hospitals, with the same distance to wall and angle of staring. For each equipment, the procedures followed the developers' recommendations. The same examiner performed the comparison between two systems in one location. For the eye-position projects, targets were placed on the wall sequentially at the pre-marked lines for different angles. For the comparison projects, 9 and 13 participants were recruited, respectively. Any participant with otologic or vestibular disorders was excluded. A total of 26 healthy participants were recruited in the eye-position experiments, 16 of which were further involved in inter-examiner tests. RESULTS Our evaluations of three different systems showed that a new vHIT system, VertiGoggles® ZT-VNG-I (VG) performed as good as the long-tested Otometrics® ICS impulse (Oto) and EyeSeeCam® (ESC). During the comparison, we validated 25-degree, instead of right ahead at 0 degree, is a better place to set the targets when torsion was applied at vertical semicircular canal planes. CONCLUSION The new VG system is good for clinical practices. Furthermore, we proposed a new protocol to set the targets 25 degrees from right ahead after tilting head 45 degrees to evaluate vertical canals during vHIT.

Supplemental Digital Content is available in the text, Background: Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed “functional cure,” based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective. Methods: A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively. Results: In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA − PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results. Conclusion: Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.

Heterostructures have broad potential application in energy conversion material and optoelectronic device since of novel interface effect and enhanced electron transport dynamics at heterointerfaces. Herein, we report a heterostructured SnS/SnO2/spherical graphene composite, in which ultrafine SnS/SnO2 nanoparticles with heterostructures are sandwiched between multi-layers of graphene sheets, exhibiting a hollow spherical architecture as a whole. Detailed electrochemical studies indicate that the molar ratio of SnS to SnO2 has great influence on the charge transport efficiency. Theoretical calculation reveals that SnS and SnO2 exhibit different work functions and the Fermi level shift is affected by the SnS/SnO2 molar ratio, thus the hybrid with the ratio close to 1.0 owns the most adsorbed lithium ions, which leads to the highest specific charge-transfer kinetics and lowest ion-diffusion resistance than other samples. Electrochemical tests show that the composite with appropriate composition delivers the best lithium storage rate performance (620 and 312.7 mAh g−1 at 1 C and 10 C). A much stable and high reversible specific capacity of 850 mAh g−1 is obtained after 200 cycles at 0.1 C. The appropriate molar ratio of nano-heterostructures and the novel sandwich hollow spherical composite structure are attributed to the excellent electrochemical performances.

This paper aims to explain the clinical features of benign paroxysmal positional vertigo (BPPV), the most common peripheral vertigo disease, from the view of vestibular pathophysiology. Firstly, it overviews several important principles in vestibular pathophysiology, including the relative density of otolith and endolymph and its spatial position relation with semicircular canal, Flourens' law, Ewald's second law, endolymph hydrodynamics caused by otolith shift, semicircular canals working as pairs, coupling of semicircular canal-extraocular muscle and central velocity storage. Secondly, use these principles to explain the clinical features of BPPV, differences between posterior and horizontal semicircular canal BPPV and the nystagmus characteristics during maneuver therapy. Finally, it presents some opinions on the diagnosis and treatment of BPPV, also based on these principles, including the differences between canalithiasis and cupulolithiasis, repositioning maneuver method and diagnosis of anterior semicircular canal BPPV. DOI: 10.3969/j.issn.1672-6731.2019.02.001

Objective To analyze the types and characteristics of nystagmus in patients with positional vertigo who were ineffective by particle repositioning maneuver (PRM) and had negative findings in MRI, and try to explore drug treatment and prevention programme. Methods A total of 43 patients with positional nystagmus were randomly treated with clonazepam or flunarizine hydrochloride. The therapeutic effect at acute phase was evaluated by comparing maximum slow phase velocity (SPV) before and after treatment. Among all patients, 21 patients with frequent attacks in recent 2 months were randomly divided into flunarizine hydrochloride prophylaxis treatment group (prophylaxis group) and blank control group (control group), followed up and recorded the average attack days of vertigo per month (days of single attack × number of attacks). The preventive effect of flunarizine hydrochloride was analyzed. Results Among 43 patients, 29 cases met the diagnostic criteria of definite and probable vestibular migraine. The main types of nystagmus were horizontal apogeotropic nystagmus (23 cases, 53.49% ), horizontal geotropic nystagmus (3 cases, 6.98% ), downbeat nystagmus (4 cases, 9.30% ) and mixed nystagmus (13 cases, 30.23%). Nystagmus lasted a longer time and lacked the characteristics of crescendo-decrescendo. After 3 d of treatment, the maximum SPV [2.40 (0.00, 17.15) °/s] of clonazepam group was significantly reduced, and the therapeutic effect at acute phase was better compared with flunarizine hydrochloride group [18.85 (1.58, 35.75) °/s; Z = -2.284, P = 0.022]. After 2 months, the average attack days of vertigo per month in prophylaxis group [1 (0, 2) d] was significantly reduced in comparison with control group [3.50 (1.50, 6.50) d; Z = -2.096, P = 0.036). Conclusions Positional vertigo with ineffective PRM and negative findings in MRI may be related to abnormal central function. After excluding the relevant contraindications, clonazepam can relieve vertigo and nystagmus in the acute phase, especially in vestibular migraine patients. For patients with frequent attacks, flunarizine hydrochloride maybe an available preventive treatment. DOI: 10.3969/j.issn.1672-6731.2019.02.003

Ménière's disease is an unexplained peripheral vestibular disease with endolymphatic hydrops as the main pathological features. Pathogenesis and pathophysiology mechanism are not clear at present. Summarizing the advances of epidemiology, pathophysiology and clinical manifestations is conducive to clinicians' understanding and in-depth study of the disease. DOI: 10.3969/j.issn.1672-6731.2019.02.002

The complete genome of a novel mycovirus, Puccinia striiformis mitovirus 1 (PsMV1), derived from the wheat stripe rust fungus Puccinia striiformis strain SCSN-10, was sequenced and analyzed. The full-length cDNA sequence is 2496 bp in length with a predicted AU content of 57.65% in the genomic RNA. Sequence analysis indicated that a single large open reading frame (ORF) is present on the positive strand when the fungal mitochondrial genetic code is used. The single ORF encodes a putative RNA-dependent RNA polymerase of 743 amino acids with a molecular mass of 84.9 kDa that shares the closest similarity with the corresponding proteins of Cronartium ribicola mitovirus 5 and Helicobasidium mompa mitovirus 1-18 (34% and 35% aa sequence identity, respectively). Phylogenetic analysis further indicated that PsMV1 is a new member of the genus Mitovirus within the family Narnaviridae. This is the first report of the full-length nucleotide sequence of a novel mitovirus, PsMV1, from the causal agent of wheat stripe rust.

A better exploring biological processes, means, and functions demands trusted information about Protein-protein interactions (PPIs). High-throughput technologies have produced a large number of PPIs data for various species, however, they are resource-expensive and often suffer from high error rates. To supplement the limitations of the traditional methods, in this paper, a sequence-based computational method is proposed to insight whether two proteins interact or not. The proposed method divides the novel PPIs prediction process into three stages: first, the position-specific scoring matrices (PSSMs) are produced by incorporating the evolutionary information; second, the 352-dimensional feature vector is constructed for each protein pair; third, effective parameters for the ensemble learning algorithm rotation forest (RF) are selected. In the proposed model, the evolutionary features are extracted from PSSM for each protein without considering any protein annotations. In addition, by using more accurate and diverse classifiers constructed by RF algorithm to avoid yielding coincident errors, one sample incorrectly divided by one classifier will be corrected by another classifier. The proposed method is evaluated in terms of accuracy, precision, sensitivity, and so on using Yeast, Human, and Pylori datasets and finds that its performance is superior to that of the competing methods. Specifically, the average accuracies achieved by the proposed method are 97.06% (Yeast), 98.95% (Human), and 89.69% (H.pylori), which improves the accuracy of PPIs prediction by 0.54%similar to 3.89% (Yeast), 1.29%similar to 3.85% (Human), and 0.22%similar to 4.85% (H.pylori). The experimental results prove that the proposed method is an effective alternative approach for predicting novel PPIs.

Objective To explore the change of serum sex hormones and 25-hydroxycholecalciferol [25-(OH)-D3 ] level in postmenopausal female patients with benign paroxysmal positional vertigo (BPPV). Methods Electrochemiluminescence (ECL) assay was employed to detect the serum levels of estradiol (E2), progesterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), and 25-(OH)-D3 in 63 female postmenopausal BPPV patients with age 50-80 years from September 1, 2015 to February 1, 2017. Spearman rank correlation analysis was used to analyze the relation between age and E2 , E2 and 25-(OH)-D3. Univariate and multivariate stepwise Logistic regression analysis were used to screen the risk factors for BPPV. Results The serum levels of E2 [15.67 (10.96, 22.15) pg/ml] and 25-(OH)-D3 [(24.24 ± 1.05) ng/ml] in BPPV group were lower than those in control group [E2: 31.78 (25.60, 39.50) pg/ml, 25-(OH)-D3: (27.62 ± 0.76) ng/ml], and the differences were statistically significant (Z = -6.768, P = 0.000; t = -2.605, P = 0.010). There was no significant difference on progesterone, LH and FSH between 2 groups. Correlation analysis showed there was no relation between E2 and 25-(OH)-D3 levels in both groups. There was a negative correlation between age and E2 in control group (rs = -0.263, P = 0.038), but no correlation in BPPV group. Multivariate Logistic regression analysis showed decreased serum E2 and 25-(OH)-D3 levels maybe the risk factors for postmenopausal female BPPV patients. Conclusions E2 and 25-(OH)-D3 deficiency are independent risk factors for BPPV in postmenopausal female patients. DOI: 10.3969/j.issn.1672-6731.2019.01.007

The effects of modified natural zeolite warm mix agent (MNZWMA) and organic viscosity reducing warm mix agent (OVRWMA) on the physical properties, short term thermal oxidation aging, long term thermal oxidation aging and UV aging properties of the crumb rubber modified bitumen (CRMB) were investigated. The results showed that MNZWMA and OVRWMA could improve the high temperature stability and the low temperature crack resistance of CRMB, respectively. During the short term thermal oxidation aging, long term thermal oxidation aging and UV aging, OVRWMA increased softening point increment (SPI) and viscosity aging index (VAI) of CRMB, however, MNZWMA decreased its SPI and VAI. The analysis of FTIR spectra indicated that MNZWMA reduced the formation of carbonyl groups and sulfoxide groups, but OVRWMA accelerated the formation of carbonyl groups and sulfoxide groups to some extent during ultraviolet aging. Therefore, MNZWMA could improve the anti-aging properties, and OVRWMA was not conducive to the anti-aging properties of CRMB.

Background and purpose To evaluate the safety and efficacy of Total neoadjuvant treatment (TNT) in patients with rectal cancer with high risk factors. Methods and materials We did this phase 2 trial in patients who were diagnosed with stage II–III rectal cancer with at least one of the high risk factors. Three cycles of induction CAPOX were followed by pelvic radiotherapy of 50.4 Gy/28 fractions and two cycles of concurrent CAPOX. Three cycles of consolidation CAPOX were delivered after radiotherapy. Primary endpoints were pathological complete response (pCR) and R0 resection. Results Fifty patients were enrolled and 47 patients were evaluable. A total of 34 patients (72.3%) completed 6 to 8 cycles of chemotherapy and 46 patients (98%) completed the planned radiotherapy. 17 patients (36%) achieved a pCR or clinical complete response (cCR). Three cCR patients (6.4%) refused the operation and selected a watch-and-wait approach. The most common grade 3 or worse adverse events were leucopenia (10.6%) and radiation dermatitis (6.4%). The major surgical complications included pelvic abscesses/infection in 2 patients (4.3%), anastomotic leakage and hemorrhage in1 patient (2.2%), respectively, which were all addressed with conservative management. Conclusions TNT is effective and safe in patients with locally advanced rectal cancer with high risk factors. Long-term efficacies of TNT need to be further evaluated. This trial is registered with Chinese Clinical Trial Registry, number ChiCTR-OIN-17012284.

PER1 is a core component of the internal time-keeping system. In the suprachiasmatic nucleus, it serves as the primary circadian pacemaker in mammalian brains. PER1 functions with other clock components to generate a feedback loop involving the transcriptional repression of gene expression to produce a circadian rhythm with an approximately 24-hour cycle. Post-transcriptional modifications (PTMs) are a basic regulatory mechanism that both perpetuate self-sustained oscillations and interpret metabolic input into circadian physiology by affecting factors such as protein stability, interactions, localization, and activity. Here we examined whether the serine/threonine protein kinase WNK3, which is expressed in a circadian rhythm, can interact and colocalize with PER1 in the SCN. In rats, WNK3 knockdown in the SCN is associated with altered sleep patterns. Moreover, WNK3 can phosphorylate PER1 to promote its degradation and is associated with circadian oscillations when PER1 is expressed in vitro.

Sn-based metal oxides and composites have been widely investigated as candidate anodes for lithium-ion batteries. However, continuous capacity fade caused by serious volumetric expansion and crystal pulverization is often noticed during lithiation and alloying processes. In this study, we design a novel heterogeneous structural composite by constructing sandwich-structured graphene hollow spheres limited Mn

Background Atypical clinical symptoms of juvenile hereditary hemochromatosis (JHH) often leads to misdiagnosis and underdiagnosis bringing ominous outcomes, even death. Methods The whole exome was sequenced and interpreted. A literature review assisted to analyze and verify the phenotype–genotype relationships. We revealed the entire process of diagnosis, treatments, and outcome of two diabetic onset of JHH families to provide new insights for genotype–phenotype relation with novel compound heterozygous mutations in the hepcidin antimicrobial peptide (HAMP, OMIM: 606464). Results Two probands were diagnosed and treated as type 1 diabetes initially because of specific symptoms and positive islet autoantibodies. Poor control of hyperglycemia and progressive symptoms occurred. Sequencing informed that the compound heterozygous and homozygous mutations c.166C>G and c.223C>T in HAMP caused type 1 diabetic‐onset JHH. The two patients accessed irregular phlebotomy treatments, and then, experienced poor prognosis. We summarized the process of overall clinical management of reported 26 cases comparing to our novel atypical diabetic onsets Juvenile Hereditary Hemochromatosis cases. Conclusion It was first reported that positive pancreatic islet autoantibodies diabetes onset of JHH resulted from loss‐of‐function mutations of HAMP, of which the atypical JHH should be differentially diagnosed with type 1 diabetes at the onset. Early administration of phlebotomy and vital organs protection and surveillance might be important for the treatment of atypical JHH., It reported the positive pancreatic islet autoantibody diabetes onset JHH case. A novel compound heterozygosity mutation in HAMP was found. Early administration of phlebotomy and vital organs protection are important.

To establish a multi-parametric regression model from four modes of ultrasound to predict the activity of Crohn's disease (CD) noninvasively. Score of 150 of the Crohn’s Disease Activity Index (CDAI) was taken as the cut-off value to divide the involved bowel segments of 51 patients into the active and inactive group. Eleven parameters from four modes of ultrasound (B-mode ultrasonography, color Doppler flow imaging, contrast-enhanced ultrasonography and shear wave elastography) were compared between the two groups to investigate the relationship between multimodal ultrasonic features and CD activity. P 2 = 0.72, P = 0.037). The multimodal ultrasound parametric regression model was designed to predict CDAI score invasively. The model has the potential to provide an alternative method for quantifying the CD activity.

Esophageal cancer (EC) is one of the most common malignancies with high incidence and mortality. Tumor-associated macrophages (TAMs) in the tumor microenvironment have been linked to the accelerated tumor progression. MicroRNAs (miR) are 19–25 nucleotide-long, noncoding RNA molecules, functioning as modulators of gene expression, and mediate a variety of biological functions, including tumor growth. In the present study, the effects and molecular mechanism of miR-155 in TAMs isolated from EC were explored. The expression of miR-155 and fibroblast growth factor-2 (FGF2) in EC tissues and cell lines were analyzed using reverse transcription-quantitative PCR (qRT-PCR) and western blot assays. TAMs were also transfected with the described constructs. Following, the culture medium from TAMs was collected for further analysis. The released FGF2, and inflammatory cytokines were quantified using ELISA. The cell viability, migrated and invaded levels were calculated through Cell Counting kit-8 (CCK8), and transwell analysis. Moreover, human umbilical vein endothelial cells (HUVEC) vasculature formation was determined using matrigel angiogenesis analysis. The results indicated that miR-155 expression was decreased in EC tissues and cell lines, while FGF2 expression was increased in comparison to those in the normal control group. Moreover, miR-155 mimics transfection up-regulated tumor necrosis factor α (TNF-α), interleukin (IL)-12 and inducible nitric oxide synthase (iNOS), while down-regulated IL-10, Arginase-1 (Arg-1) and IL-22 levels in the culture medium from TAMs. And enhancing miR-155 expression in TAMs suppressed the cell viability, migration and invasion of ECA109 cells and reduced the angiogenesis. Nevertheless, over-expressing FGF2 abolished the role of miR-155 in cancer cell survival, migration, invasion as well as angiogenesis. Our findings indicated that miR-155-regulated FGF2 expression from TAMs suppressed EC cell proliferation, migration, invasion and inhibited vasculature formation. Thus, miR-155-modulated FGF2 might be a potential therapeutic target to prevent EC progression.

Testis-specific PRSS55 is a highly conserved chymotrypsin-like serine protease among mammalian species. So far, the physiological function of PRSS55 remains unknown. Here, we show that PRSS55 is a GPI-anchored membrane protein, specifically expressed in adult mouse testis and mainly observed in the luminal side of seminiferous tubules and sperm acrosome. Mice deficient for Prss55 develop male infertile with normal reproduction-related parameters observed. Interestingly, in vivo fertilization rate of Prss55−/− males is dramatically decreased, possibly due to incapable migration of Prss55−/− sperm from uterus into oviduct. However, in vitro fertilization rate has no difference between two genotypes although Prss55−/− sperm presents defective recognition/binding to zona-intact or zona-free oocytes. Further study reveals that mature ADAM3 is almost undetectable in Prss55−/− sperm, while precursor ADAM3 remains unchanged in the testis. However, it is shown that ADAM3 has no interaction with PRSS55 by immunoprecipitation with anti-PRSS55 antibody. The expression levels of several proteins known to be related to the observed phenotypes remain comparable between wt and Prss55−/− mice. Moreover, we found that Prss55 deficiency has no effect on PRSS37 or vice versa albeit two mutant males share almost the same phenotypes. Microarray analysis reveals a total of 72 differentially expressed genes in Prss55−/− testis, most of which are associated with cellular membrane and organelle organization, protein transport and complex assembly, and response to stimulus and signaling. In conclusion, we have demonstrated that PRSS55 plays vital roles in regulating male fertility of mice, including in vivo sperm migration and in vitro sperm–egg interaction, possibly by affecting the maturation of ADAM3 in sperm and the expression of multiple genes in testis. Electronic supplementary material The online version of this article (10.1007/s00018-018-2878-9) contains supplementary material, which is available to authorized users.

BACKGROUND Despite of intensive efforts, the tumor progression of ovarian cancer has not yet been fully understood. Various studies suggest that an effective experimental model system In Vitro to mimic microenvironment in vivo and the fabrication of cell pattern formation In Vitro are of great importance for the ovarian cancer research. METHODS This study cultivates SKOV3, A2780 and A2780/DDP ovarian cancer cell lines in RADA16-I peptide hydrogel to obtain 3D-precultured cancer cells and fabricate a type of miniature cell pattern formation In Vitro on RADA16-I peptide nanofibercoated coverslip by in situ AFM analysis and chemosensitivity assay in vitro. RESULTS SKOV3, A2780 and A2780/DDP cells were regularly cultivated in RADA16-I peptide hydrogel, respectively, and present defined cellular characteristics, such as small cell colonies, cell clusters and cell aggregates, etc. On coverslip coated with RADA16-I peptide nanofiber, three 3D-precultured cell lines were flat and spread on coverslips and the regular topographic images by AFM were obtained. The chemosensitivity assay of three ovarian cancer cell lines were significantly different in RADA16-I peptide-coated coverslips compared with 2D dish plates. CONCLUSIONS By 3D cell culture of ovarian cancer cell lines in RADA16-I peptide hydrogel In Vitro, the cell culture model systems was fabricated. The miniature cell pattern formation In Vitro on peptide nanofiber-coated coverslip was particularly useful experiemental model systems to be served as a valuable methodology for studying ovarian cancer biology.

The contents of hydroxycinnamoylated catechins (HCCs) in tea leaves have yet to be thoroughly investigated. Herein, four HCCs, (−)-epicatechin 3-O-p-coumaroate (EC-pC), (−)-epicatechin 3-O-caffeoate (EC-C), (−)-epigallocatechin 3-O-p-coumaroate (EGC-pC), and (−)-epigallocatechin 3-O-caffeoate (EGC-C) were synthesized as standards through an improved route and then identified in leaves of 40 and quantified in 20 tea cultivars using ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS). EC-C and EC-pC were synthesized for the first time. This study found that HCCs were widely present in the two varieties of tea, Camellia sinensis var. sinensis (CSS) and var. assamica (CSA). The contents of total four HCCs and EGC-pC were higher in CSS (729–1398 mg/kg for total HCCs, 483–1052 mg/kg for EGC-pC), while EC-C was higher in CSA (65–176 mg/kg) cultivars, suggesting that EC-C and EGC-pC could be used as biochemical markers to differentiate CSS from CSA tea cultivars. Changes in HCCs contents were detected from the tea leaves collected from April to October, indicating that tea leaves harvested in August would have the highest HCCs content.

Solid electrolyte membrane plays a vital role in the application of all-solid-state batteries. In this paper, composite electrolyte membranes incorporating commercial submicron Li6.75La3Zr1.75Ta0.25O12 (LLZTO) are prepared by solvent-free hot rolling method. It is found that the addition of LLZTO to the PEO-LiTFSI-based electrolyte can effectively reduce the crystallinity of PEO, improve the ion conductivity, voltage window, mechanical properties and interfacial stability of the composite solid electrolyte membrane. The composite electrolyte membrane with the optimal LLZTO content of 10 wt% exhibits a maximum ionic conductivity of 3.03 × 10−4 S cm−1 at 55 °C and a maximum elongation break of 74.8%. And also, the lithium symmetric cell assembled with 10 wt% LLZTO membrane exhibits the lowest polarization voltage and the best cycle performance, which can be attributed to the enhanced mechanical properties of the membrane and the lower and stable interfacial resistance between the membrane and lithium metal. The all-solid-state LiFePO4/Li batterie delivers a high specific capacity of 155.8 mAh g−1 at 0.1C rate at 55 °C, and exhibits excellent cycle performance and rate performance. In addition, the pouch cells assembled with PEO-LiTFSI-10LLZTO composite electrolyte membrane can still maintain the pristine voltage of 3.39 V and power light-emitting diodes (LEDs) under harsh conditions such as cutting, showing an excellent safety performance.

Under the interval-valued hesitant fuzzy information environment, we investigate a multiattribute group decision making (MAGDM) method with continuous entropy weights and improved Hamacher information aggregation operators. Firstly, we introduce the axiomatic definition of entropy for interval-valued hesitant fuzzy elements (IVHFEs) and construct a continuous entropy formula on the basis of the continuous ordered weighted averaging (COWA) operator. Then, based on the Hamachert-norm andt-conorm, the adjusted operational laws for IVHFEs are defined. In order to aggregate interval-valued hesitant fuzzy information, some new improved interval-valued hesitant fuzzy Hamacher aggregation operators are investigated, including the improved interval-valued hesitant fuzzy Hamacher ordered weighted averaging (I-IVHFHOWA) operator and the improved interval-valued hesitant fuzzy Hamacher ordered weighted geometric (I-IVHFHOWG) operator, the desirable properties of which are discussed. In addition, the relationship among these proposed operators is analyzed in detail. Applying the continuous entropy and the proposed operators, an approach to MAGDM is developed. Finally, a numerical example for emergency operating center (EOC) selection is provided, and comparative analyses with existing methods are performed to demonstrate that the proposed approach is both valid and practical to deal with group decision making problems.

// Hongbo Chen 1, 2, 6, * , Liqiao Han 3, 1, * , Hsiangi Tsai 1, 2, * , Zhiwei Wang 4 , Yanping Wu 1, 2 , Yanhong Duo 1 , Wei Cao 1, 2 , Lijun Chen 5 , Zhirong Tan 3 , Ning Xu 3 , Xianzhang Huang 3 , Junhua Zhuang 3 , Laiqiang Huang 1, 2 1 The Shenzhen Key Lab of Gene and Antibody Therapy, Center for Biotechnology & Biomedicine, Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China 2 School of Life Sciences, Tsinghua University, Beijing 100084, China 3 Department of Laboratory Science, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China 4 Department of Laboratory Medicine, The Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou 511447, China 5 Technology Center of Guangxi Entry-Exit Inspection and Quarantine Bureau, Nanning 530021, China 6 Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada * These authors have contributed equally to this work Correspondence to: Xianzhang Huang, email: huangxz020@163.com Junhua Zhuang, email: zjh2208@163.com Laiqiang Huang, email: huanglq@tsinghua.edu.cn Keywords: PICT-1, nucleolus, DNA damage, nucleolar stress Received: June 13, 2016 Accepted: October 19, 2016 Published: November 04, 2016 ABSTRACT PICT-1 is an essential ribosome biogenesis factor whose loss induces p53 accumulation and apoptosis. Here, we show that DNA damage changes PICT-1 localization and decreases PICT-1 protein levels via the proteasome pathway. Two important phosphatidylinositol 3-kinase-like kinases (PIKKs), ataxia-telangiectasia mutated (ATM) and the Ku70 subunit of DNA-dependent protein kinase (DNA-PK), co-localize and interact with PICT-1 in the nucleolus. Computational prediction of phosphorylation sites and detection using an anti-phospho-substrate antibody suggest that PICT-1 might be a substrate of PIKKs. PICT-1 S233 and T289 were identified as the key phosphorylation sites in this pathway, as mutating both to alanine abolished UVB-induced increase of PICT-1 phosporylation. Inhibition of PIKKs or ATM (with wortmannin and KU55933, respectively) prevented the agglomeration and degradation of PICT-1, suggesting that ATM is a key regulator of PICT-1. PICT-1(S233A, T289A) demonstrated marked resistance to DNA damage-induced agglomeration and loss of PICT-1. Phosphomimetic PICT-1 (S233D, T289D) showed a different nuclear distribution and was more rapidly degraded after DNA damage than wild-type PICT-1. Furthermore, both phosphorylation and degradation of PICT-1 released RPL11 from the nucleolus to the nucleoplasm, increased binding of RPL11 to MDM2, and promoted p53 accumulation and apoptosis in an ATM-dependent manner after DNA damage. These data indicate that PICT-1 is a major nucleolar sensor of the DNA damage repair response and an important upstream regulator of p53 via the RPL11-MDM2-p53 pathway.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is not only a common consequence of stroke but also an important factor for adverse prognosis of patients. Biochemical indicators such as blood lipids and blood pressure are affected by many factors, and the ability of evaluating the progress of patients with PSCI is insufficient. Therefore, it is necessary to find sensitive markers for predicting the progress of patients and avoiding PSCI. Recent studies have shown that β-amyloid protein 1-42 (Aβ1-42) and thyroid hormone levels are closely related to PSCI, which may be the influencing factors of PSCI, but there are few related studies. AIM: To investigate the relationship between serum levels of Aβ and thyroid hormones in acute stage and PSCI and its predicted value. METHODS: A total of 195 patients with acute cerebral infarction confirmed from June 2016 to January 2018 were enrolled in this study. Baseline data and serological indicators were recorded to assess cognitive function of patients. All patients were followed up for 1 year. Their cognitive functions were evaluated within 1 wk, 3 mo, 6 mo and 1 yr after stroke. At the end of follow-up, the patients were divided into PSCI and non-PSCI according to Montreal cognitive assessment score, and the relationship between biochemical indexes and the progression of PSCI was explored. RESULTS: Compared with patients with non-PSCI, the levels of Aβ1-42, triiodothyronine (T(3)) and free thyroxin were lower in the patients with PSCI. Repeated measures analysis of variance showed that the overall content of Aβ1-42 and T(3) in PSCI was also lower than that of the non-PSCI patients. Further analysis revealed that Aβ1-42 (r = 0.348), T(3) (r = 0.273) and free thyroxin (r = 0.214) were positively correlated with disease progression (P < 0.05), suggesting that these indicators have the potential to predict disease progression and outcome. Cox regression analysis showed that Aβ1-42 and T(3) were important factors of PSCI. Then stratified analysis showed that the lower the Aβ1-42 and T(3), the higher risk of PSCI in patients who were aged over 70, female and illiterate. CONCLUSION: Aβ1-42 and T3 have the ability to predict the progression of PSCI, which is expected to be applied clinically to reduce the incidence of PSCI and improve the quality of life of patients.

In this paper, a car room temperature control method based on single user personalized comfort is proposed: Firstly, a smartphone application based on android platform is designed to collect user’s information and their personalized comfort dataset are established. Secondly, the DENFIS (Dynamic Evolving Neural-Fuzzy Inference System) method is used. This method helps to extract the fuzzy inference system and obtain the control targets according the dataset. Finally, MATLAB is used to verify the method. The result shows that the control target obtained by this method basically meets the needs of the user.

Background Ammonium transporters (AMTs), a family of proteins transporting ammonium salt and its analogues, have been studied in many aspects. Although numerous studies have found that ammonium affects the interaction between plants and pathogens, the role of AMTs remains largely unknown, especially that of the AMT2-type AMTs. Results In the present study, we found that the concentration of ammonium in wheat leaves decreased after infection with Puccinia striiformis f. sp. tritici (Pst), the causal agent of stripe rust. Then, an AMT2-type ammonium transporter gene induced by Pst was identified and designated as TaAMT2;3a. Transient expression assays indicated that TaAMT2;3a was located to the cell and nuclear membranes. TaAMT2;3a successfully complemented the function of a yeast mutant defective in NH4+ transport, indicating its ammonium transport capacity. Function of TaAMT2;3a in wheat-Pst interaction was further analyzed by barley stripe mosaic virus (BSMV)-induced gene silencing. Pst growth was significantly retarded in TaAMT2;3a-knockdown plants, in which ammonium in leaves were shown to be induced at the early stage of infection. Histological observation showed that the hyphal length, the number of hyphal branches and haustorial mother cells decreased in the TaAMT2;3a knockdown plants, leading to the impeded growth of rust pathogens. Conclusions The results clearly indicate that the induction of AMT2-type ammonium transporter gene TaAMT2;3a may facilitates the nitrogen uptake from wheat leaves by Pst, thereby contribute to the infection of rust fungi. Electronic supplementary material The online version of this article (10.1186/s12870-019-1841-8) contains supplementary material, which is available to authorized users.

Group decision making with intuitionistic fuzzy preference information contains two key issues: acceptability measurement and priority weight determination. In this paper, we investigate the above two issues with respect to multiplicative interval-valued intuitionistic fuzzy preference relation (IVIFPR). Firstly, a consistency index is defined to measure the multiplicative consistency degree of IVIFPR and an optimization model is established to improve the consistency degree of IVIFPR to an acceptable one. Next, in terms of priority weight determination, an error-analysis-based extension method is proposed to obtain priority weight vector from the acceptable IVIFPR. For GDM problems, decision makers’ weights are derived by the proposed multiplicative consistency index. Subsequently, the collective IVIFPR is obtained by using an interval-valued intuitionistic fuzzy (IVIF) weighted averaging operator. Finally, a step-by step algorithm for GDM with IVIFPRs is given, and an example of enterprise innovation partner selection is analyzed, and comparative analyses with existing approaches are performed to demonstrate that the proposed algorithm is both effective and practical in dealing with GDM problems.

Background: Health care workers (HCWs) seek, treat, and care for patients living with HIV/AIDS on a daily basis and thus face a significant risk to work-related infections. To assess the knowledge, attitude, and practices regarding occupational HIV exposure and protection among HCWs in low HIV prevalence areas of rural China. Methods: A cross-sectional questionnaire survey was carried out among all medical units in Pucheng County, Shaanxi, China. Results: Response rate of this study was 94%. The average overall knowledge score of HCWs was 10.9 of 21.0. Deficiencies in general, transmission, exposure, and protection knowledge were identified among HCWs at all levels. A high rate of occupational exposure (85%) and lack of universal precautions practice behavior were recorded. Significant predictors of universal precautions practice behavior were female sex, prior training, and greater knowledge about HIV/AIDS. Conclusion: Health care workers at various levels have inadequate knowledge on HIV/AIDS and do not practice universal precautions. Nurses and medical technicians at the county level faced more occupation risk than other HCWs. The key of AIDS training for different levels of HCWs should be distinguished.

Objective To assess circadian characteristics of spontaneous physical activity and deep body temperature in narcoleptic patients. Methods Fourteen narcoleptic patients and 14 healthy age- and sex-matched control subjects were enrolled. Nocturnal polysomnography (PSG) was recorded, followed by standard multiple sleep latency test (MSLT). Then all subjects were required to wear the actigraphy (actiwatch) at home with continuous monitoring of spontaneous physical activity for 1-2 weeks and complete the daily sleep record. All subjects' deep body temperatures were measured at 20 time points. Results In comparison with control subjects, PSG data suggested narcoleptic patients had significantly longer time in bed at night (P = 0.008), decreased sleep efficiency (P = 0.001), increased awakenings (P = 0.000), extended wake time after sleep onset (P = 0.000) and sleep onset rapid eye movement period (SOREMP, P = 0.002). MSLT data suggested decreased average sleep latency (P = 0.000) and increased SOREMPs (P = 0.000). Actigraphy data suggested increased nocturnal activity and nocturnal activity per hour (P = 0.000, for all), decreased daytime activity and daytime activity per hour (P = 0.000, for all) and increased nocturnal activity per hour/daytime activity per hour (P = 0.000, for all). The deep body temperature in both groups showed significant circadian rhythms. The differences in mesor, amplitude and peak phase of deep body temperature between 2 groups had no statistical significance (P = 0.177, 0.730, 0.488). Conclusions Narcoleptic patients are characterized by impaired circadian rhythm of sleep-wake and spontaneous physical activity. The limited effects on deep body temperature suggest the relative conservation of thermoregulation in narcolepsy. DOI: 10.3969/j.issn.1672-6731.2016.07.010

Importance The role of locoregional radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) is unclear. Objective To investigate the efficacy and safety of locoregional radiotherapy in de novo mNPC. Design, Setting, and Participants Patients with biopsy-proven mNPC, who demonstrated complete or partial response (RECIST v1.1) following 3 cycles of cisplatin and fluorouracil chemotherapy, were enrolled. Eligible patients were randomly assigned (1:1) to receive either chemotherapy plus radiotherapy or chemotherapy alone. Overall, 126 of 173 patients screened were eligible to the study, and randomized to chemotherapy plus radiotherapy (n = 63) or chemotherapy alone (n = 63). Median (IQR) follow-up duration was 26.7 (17.2-33.5) months. Interventions The chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m2over 120 hours and 100 mg/m2intravenous cisplatin on day 1, administered every 3 weeks for 6 cycles. Patients assigned to the chemotherapy plus radiotherapy group received intensity-modulated radiotherapy (IMRT) after chemotherapy. Main Outcomes and Measures The primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety. Results Overall, 126 patients were enrolled (105 men [83.3%] and 21 women [16.7%]; median [IQR] age, 46 [39-52] years). The 24-month OS was 76.4% (95% CI, 64.4%-88.4%) in the chemotherapy plus radiotherapy group, compared with 54.5% (95% CI, 41.0%-68.0%) in the chemotherapy-alone group. The study met its primary end point of improved OS (stratified hazard ratio [HR], 0.42; 95% CI, 0.23-0.77;P = .004) in favor of chemotherapy plus radiotherapy. Progression-free survival was also improved in the chemotherapy plus radiotherapy group compared with the chemotherapy-alone group (stratified HR, 0.36; 95% CI, 0.23-0.57). No significant differences in acute hematological or gastrointestinal toxic effects were observed between the treatment arms. The frequency of acute grade 3 or higher dermatitis, mucositis, and xerostomia was 8.1%, 33.9%, and 6.5%, respectively, in the chemotherapy plus radiotherapy group. The frequency of late severe grade 3 or higher hearing loss and trismus was 5.2% and 3.4%, respectively, in the chemotherapy plus radiotherapy group. Conclusions and Relevance In this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC. Trial Registration ClinicalTrials.gov Identifier:NCT02111460

High capacity lithium-rich layered oxide Li1.2Ni0.13Co0.13Mn0.54O2 cathode material is considered as a most promising cathode material for lithium ion batteries. However, its application is greatly limited due to the characteristics of low initial coulombic efficiency and poor low-temperature performance. In this study, AlF3-coated Li1.2Ni0.13Co0.13Mn0.54O2 has been prepared via a facile wet chemical process. It is found that a dense AlF3 layer with a nanoscale thickness is covered on the surface of Li1.2Ni0.13Co0.13Mn0.54O2 particles, building a rapid lithium transport bridge for adjacent active materials and reducing side reaction between the electrolyte and active material. Compared to the pristine Li1.2Ni0.13Co0.13Mn0.54O2, 2% AlF3-coated sample exhibits higher discharge capacity and initial coulombic efficiency (86.7%). Meanwhile, 2% AlF3-coated sample displays obviously superior rate capability at 0 °C and higher capacity retention at −10 and −20 °C. The improvement of low-temperature performance can reasonably be attributed to the formation of the spinel structure and the LiAlO2 on the surface of the active materials, which can improve the electronic conductivity and lithium ion conductivity of the cathode material, respectively.

Background To evaluate safety and efficacy of transpupillary silicone oil removal combined with micro-incision phacoemulsification cataract surgery, and to compare results of transpupillary with 23-gauge three-port vitrectomy approach. Methods Consecutive cases that underwent silicone oil removal using either transpupillary or three-port approach in combination with micro-incision phacoemulsification cataract surgery were retrospectively reviewed. The main outcome measures were postoperative detachment rate, silicone oil residuals, best corrected visual acuity (BCVA) and intraocular pressure (IOP). Results A total of 64 cases were included, 19 in transpupillary and 45 in three-port. Postoperative detachment rate within 3 months in transpupillary versus three-port was 15.8% versus 4.4% (p = 0.14), Silicone oil residuals was 7.4 ± 3.2% versus 7.1 ± 2.8% (transpupillary vs. three-port, p = 0.71). Preoperative versus postoperative BCVA (logMAR) was 1.49 ± 0.61 versus 1.42 ± 0.61 in transpupillary approach (p = 0.28) and 1.53 ± 0.48 versus 1.45 ± 0.57 in three-port approach (p = 0.11). Transpupillary approach resulted in lower IOP at postoperative day 2 (12.2 ± 2.3 mmHg vs. 13.5 ± 2.2 mmHg, p

This research is to explore the perfusion time-intensity curve parameters of a lung adenocarcinoma xenograft into nude mouse model with contrast enhanced ultrasonography(CEUS);and to investigate the angiogenesis features of tumor at different growth time.Twenty one lung adenocarcinoma xenografted nude mice were divided into three groups and inculcated with human lung adenocarcinoa.Time window for examining CEUS were respectively in7-day,14-day and 28-day.The perfusion parameters including rise time(RT),peak intensity(PI),area under the curve(AUC)of lung tumor were obtained on CEUS images by using off-line software Q lab.Immunohistochemically staining for CD34 was used to observe the microvessel density(MVD).The 7-day group had the highest AUC and PI;AUC and PI of 14-day and 28-day group decreased gradually(P0.05).RT was increased as tumor growth.In tumor with necrosis,AUC and PI of non-necrosis part were also larger than necrosis part(P0.05).Immunohistochemically staining for CD34 of all tumors reflected that the density of microvessels in necrosis tumor was significantly higher than those without necrosis(7.50±3.44 vs.12.44±5.74,P=0.034).Pearson correlation indicated that PI was positively related with MVD(r=0.668,P=0.008).Lung adenocarcinoma perfusion characteristic can be accessed from time-intensity curve parameters by using noninvasively and non-radiative contrast enhanced ultrasonography.Time-intensity curve parameters including AUC,PI and RT may reflect tumor angiogenesis.

Despite of intensive efforts, the tumor progression of ovarian cancer has not yet been fully understood. Various studies suggest that an effective experimental model system In Vitro to mimic microenvironment in vivo and the fabrication of cell pattern formation In Vitro are of great importance for the ovarian cancer research.This study cultivates SKOV3, A2780 and A2780/DDP ovarian cancer cell lines in RADA16-I peptide hydrogel to obtain 3D-precultured cancer cells and fabricate a type of miniature cell pattern formation In Vitro on RADA16-I peptide nanofibercoated coverslip by in situ AFM analysis and chemosensitivity assay in vitro.SKOV3, A2780 and A2780/DDP cells were regularly cultivated in RADA16-I peptide hydrogel, respectively, and present defined cellular characteristics, such as small cell colonies, cell clusters and cell aggregates, etc. On coverslip coated with RADA16-I peptide nanofiber, three 3D-precultured cell lines were flat and spread on coverslips and the regular topographic images by AFM were obtained. The chemosensitivity assay of three ovarian cancer cell lines were significantly different in RADA16-I peptide-coated coverslips compared with 2D dish plates.By 3D cell culture of ovarian cancer cell lines in RADA16-I peptide hydrogel In Vitro, the cell culture model systems was fabricated. The miniature cell pattern formation In Vitro on peptide nanofiber-coated coverslip was particularly useful experiemental model systems to be served as a valuable methodology for studying ovarian cancer biology.

Puccinia striiformis f.sp. tritici (Pst) is the causal agent of stripe (yellow) rust on wheat. It seriously threatens wheat production worldwide. The obligate biotrophic fungus is highly capable of producing new virulent races that can overcome resistance. Studying the inheritance of Pst virulence using the classical genetic approach was not possible until the recent discovery of its sexual stage on barberry plants. In the present study, 127 progeny isolates were obtained by selfing a representative Chinese Yellow Rust (CYR) race, CYR32, on Berberis aggregate. The parental isolate and progeny isolates were characterized by testing them on 25 wheat lines with different Yr genes for resistance and 10 simple sequence repeat (SSR) markers. The 127 progeny isolates were classified into 27 virulence phenotypes (VPs), and 65 multi-locus genotypes (MLGs). All progeny isolates and the parental isolate were avirulent to Yr5, Yr8, Yr10, Yr15, Yr24, Yr26, Yr32, and YrTr1; but virulent to Yr1, Yr2, Yr3, Yr4, Yr25, Yr44, and Yr76. The VPs of the parental isolate to nine Yr genes (Yr6, Yr7, Yr9, Yr17, Yr27, Yr28, Yr43, YrA, and YrExp2) and the avirulence phenotype to YrSP were found to be heterozygous. Based on the segregation of the virulence/avirulence phenotypes, we found that the VPs to Yr7, Yr28, Yr43, and YrExp2 were controlled by a dominant gene; those to Yr6, Yr9, and YrA (Yr73, Yr74) by two dominant genes; those to Yr17 and Yr27 by one dominant and one recessive gene; and the avirulence phenotype to YrSP by two complementary dominant genes. Molecular mapping revealed the linkage of 10 virulence/avirulence genes. Comparison of the inheritance modes of the virulence/avirulence genes in this study with previous studies indicated complex interactions between virulence genes in the pathogen and resistance genes in wheat lines. The results are useful for understanding the plant-pathogen interactions and developing wheat cultivars with effective and durable resistance.

Puccinia striiformis f. sp. tritici (Pst), the causal agent of wheat stripe rust, is an obligate pathogen that causes significant yield losses worldwide. In order to profile the change of the proteome during uredospore germination of Pst, proteins from uredospores and germtubes (germlings) were isolated and quantified by iTRAQ (isobaric tag for relative and absolute quantitation) technology. Among the 1548 proteins identified, there were 64 and 54 proteins up- and down-regulated during uredospore germination respectively. Proteins involved in catabolic process, energy production and transport were found to be specially accumulated in germlings, which was an indication of metabolic transition from dormancy to germination. While, proteins involved in protein metabolic process were largely down-regulated, suggesting fewer proteins were needed for uredospore germination. Additionally, a number of down-regulated proteins exhibited increasing mRNA level during germination, suggesting relative less correlation between proteins and mRNAs in dormant uredospores.