[Classification of childhood arterial ischemic stroke].

The etiology of childhood arterial ischemic stroke is complex, and identifying the underlying cause is crucial for optimizing treatment and preventing recurrence. Currently, the classification methods for childhood arterial ischemic stroke are largely based on data from international studies, but a unified consensus have not yet been reached. This paper reviews the existing classification methods and their subtype definitions, and points out some doubts and ambiguities. On this basisi, combined with the data collected by Beijing Children's Hospital on Chinese children with arterial ischemic stroke, a new classification method (COIST) was proposed according to the etiology and pathogenesis, namely: inflammation (I), abnormal vascular structure (S), thrombophilia (T), heart disease (C), other identifiable causes (O), and uncertain causes; and various subtypes are listed. It is hoped that this new classification method can attract the attention and discussion of domestic colleagues, with the aim of further refinement, in order to help clinicians better understand and quickly identify the etiologies of childhood ischemic stroke.

Endoscopic sinus surgery improves Eustachian tube function in patients with chronic rhinosinusitis: a multicenter prospective study.

BACKGROUND: Patients with chronic rhinosinusitis (CRS) often have Eustachian tube dysfunction (ETD) symptoms. This study aimed to prospectively investigate the effect of endoscopic sinus surgery (ESS) on improvement of Eustachian tube function in CRS patients with ETD from a Chinese population and determine factors associated with improvement. METHODS: A prospective study was performed in CRS patients with ETD who underwent ESS from 3 tertiary medical centers in south China. The Eustachian tube Dysfunction Questionnaire 7 (ETDQ-7), Sinonasal Outcome Test 22 (SNOT-22), tympanograms, endoscopic findings and Valsalva maneuver were recorded and analyzed preoperatively and postoperatively at 8-12 weeks. RESULTS: A total of 70 CRS patients with ETD were included in this study. The ETDQ-7 score and the ability of positive Valsalva maneuver in CRS patients were significantly improved postoperatively at 8-12 weeks. The number of patients with type A tympanogram was increased postoperatively. Reduced Eustachian tube mucosal inflammation was also observed postoperatively. In addition, ESS appeared to reverse slight tympanic membrane atelectasis after 8-12 weeks. Moreover, improvement in tympanogram was presented in more than half of CRS patients with concomitant otitis media with effusion postoperatively at 8-12 weeks. Univariate and multivariate analysis revealed failure of normalization of ETDQ-7 postoperatively was associated with concomitant allergic rhinitis and higher preoperative SNOT-22 score. CONCLUSIONS: This study confirms Eustachian tube function is often improved after ESS in CRS patients with ETD. Concomitant allergic rhinitis and higher preoperative SNOT-22 score are associated with failure of normalization of ETD symptoms.

[Long-term rituximab treatment of refractory idiopathic inflammatory myopathy: A report of 3 cases].

Idiopathic inflammatory myopathies are a group of rare but serious diseases. The treatment of refractory idiopathic inflammatory myopathy is always challenging, especially in children. Three cases of refractory idiopathic inflammatory myopathy treated by rituximab were reported and discussed with the review of relevant literature. All were female with on-set age of 8 years and 6 months, 11 years and 7 months, 4 years and 2 months old, respectively. All had acute onset, presenting with progressive and severe muscle weakness. All lost ambulation within 1 or 2 months, with difficult swallowing and low voice. Respiratory distress occurred in case 2 after an attack of asphyxia due to an aspiration of sputum, and ventilator support was required for 1 month. Rashes were detected at the initial stage of the disease in cases 2 and 3. Patient 2 showed facial erythematous papules, spreading to her neck and hands. Patient 3 showed purplish eyelids with peri-orbital swelling, generalized edema involving all her limbs. Creatine kinase (CK) levels were markedly elevated in all the patients, ranging from 6 000 IU/L to 28 819 IU/L. Anti-SRP antibody was identified in cases 1, and anti-NXP2 antibodies were confirmed in cases 2 and 3. MRI of both thighs in all the patients showed profound muscle and fascial edema. Muscle pathology of patient 1 showed prominent fiber variation and endomysial fibrosis, with overexpression of MHC-Ⅰ. While muscle pathology in patients 2 and 3 showed scattered fiber necrosis, regeneration, endomysial edema without inflammatory cell infiltration. All the patients were diagnosed with idiopathic inflammatory myopathy and failed to the initial treatment including adequate glucocorticoids and high-dose immunoglobulin therapy. Other immunosuppressants (methotrexate, cyclophosphamide) were also tried in cases 2 and 3 with poor response. Then all the patients were treated with rituximab combined with glucocorticoids. Patient 1 regained normal strength and discontinued rituximab at the end of her last follow-up (2 years and 7 mouths). Though calcinosis developed during the follow-up period, significant improvement was noticed in cases 2 and 3 (both regained the ability to walk independently) at the end of their last follow-up after 2 years and 8 months, 3 years and 2 months respectively. Long-term rituximab therapy may improve the prognosis of refractory idiopathic inflammatory myopathy, especially with positive anti-SRP and anti-NXP2 antibodies.

Perimysial microarteriopathy in dermatomyositis with anti-nuclear matrix protein-2 antibodies.

BACKGROUND AND PURPOSE: Dermatomyositis (DM) with anti-nuclear matrix protein-2 (NXP-2) antibodies usually shows multifocal ischaemic lesions in muscle. Here, we aimed to investigate the microarteriopathy underlying muscle ischaemia in anti-NXP-2-positive DM. METHODS: A total of 16 patients diagnosed with anti-NXP-2-positive DM were investigated by muscle biopsy. A total of 13 patients with DM with other myositis-specific antibodies and 11 normal controls were included for comparison. Immunofluorescence assays were performed to localize endothelial cells, smooth muscle cells and pericytes, and to determine lesions in myofibers and microvessels by vascular endothelial growth factor and myxovirus resistance protein A (MxA). Electron microscopy was carried out to assess ultrastructure alterations. RESULTS: Subcutaneous edema, severe muscle weakness and dysphagia together with elevated creatine kinase, D-dimer and triglyceride levels, and decreased albumin levels were found in anti-NXP-2-positive DM. Muscle ischaemia included regional muscle edema, perifascicular atrophy, microinfarcts and focal punched-out vacuoles. The density of arterioles was higher in anti-NXP-2-positive DM (P ï¼œ 0.05). Perimysial arterioles with thickened vascular wall, thrombosis and lipid accumulation were found in the vascular wall of diseased perimysial arterioles. The frequency of diseased arterioles and thrombosis was higher in anti-NXP-2-positive DM (P < 0.05). Sarcoplasmic vascular endothelial growth factor and MxA expression was observed in multifocal ischaemic lesions. MxA was present in endothelial and smooth muscle cells of the diseased arterioles and pericytes. Electron microscopy confirmed damaged capillaries and tubuloreticular structures. CONCLUSIONS: Our research suggested that perimysial arterioles were most commonly involved in anti-NXP-2-positive DM, which led to muscle ischaemia.

Structural maintenance of chromosomes 2 is identified as an oncogene in bladder cancer in vitro and in vivo.

Taurine upregulated gene 1 (TUG1) has been found to promote bladder cancer cell growth in our recent research. In this study, TUG1-depleted bladder cancer cells were used to identify potent players in bladder cancer. Human gene expression arrays were used for transcriptome profiling of TUG1-depleted bladder cancer cells. Cell proliferation was analyzed by MTT assay. Cell apoptosis and cell cycle were analyzed by flow cytometry. Colony formation assay was used to observe the changes of colony formation rates. Xenograft formation assay was performed in nude mice. Immunohistochemical staining was used to test the gene expression levels in tissues from bladder cancer patients. We found that deregulated genes were strongly enriched in cell cycle or pathways in cancer in TUG1-depleted bladder cancer cells. Structural maintenance of chromosomes 2 (SMC2) was inhibited after TUG1 knockdown. The depletion of TUG1 or SMC2 led to G2/M phase arrest in bladder cancer cells. SMC2 depletion inhibited bladder cancer cell proliferation, promoted apoptosis, decreased colony formation, and reduced tumor growth in xenograft nude mice. Overexpression of SMC2 restored the growth of TUG1-depleted cells. The expression levels of SMC2 were higher in human bladder cancer tissues than that in paired normal tissues. Our data suggest that SMC2 is an oncogene in bladder cancer and depletion of SMC2 might have potential therapeutical significance in bladder cancer.

Quantitative Analysis of DCE-MRI and RESOLVE-DWI for Differentiating Nasopharyngeal Carcinoma from Nasopharyngeal Lymphoid Hyperplasia.

To explore the ability of quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) analysis and readout segmentation of long variable echo-trains diffusion weighted imaging (RESOLVE-DWI) to distinguish nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoid hyperplasia (NPLH). Twenty-five patients with NPC and 30 patients with NPLH were evaluated. Three quantitative DCE-MRI parameters (Ktrans, Kep and Ve) and the apparent diffusion coeffcient (ADC) of lesions were calculated. The two independent samples t test or Mann-Whitney U test was used to compare the parameters between NPC and NPLH group. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic ability for distinguishing NPC from NPLH. A P value less than 0.05 was considered statistically significant. The difference in Ktrans value between the NPC group and the NPLH group was statistically significant, and the value of the NPC group was larger than that of the NPLH group. There was no statistical difference in Kep and Ve between the two groups. The ADC value of NPC group was smaller than that of NPLH group, and the difference was statistically significant. ROC curve analysis showed that both Ktrans and ADC were effective in diagnosing NPC and the area under the curve (AUC) was 0.773 and 0.704, respectively. In addition, the combination of Ktrans and ADC demonstrated the obviously improved AUC of 0.884. DCE-MRI and RESOLVE-DWI are effective in differentiating NPC from NPLH, especially the combination of the two models.

[Meta-analysis on tetanus antibody protection rate of healthy population born after 1978 in China].

Objective: Meta-analysis was conducted on the tetanus antibody protection rate of healthy population born after 1978 in China (data from Hong Kong, Macao and Taiwan was excluded, the same below). Methods: Search the data on China's tetanus antibody level which were published in China National Knowledge Infrastructure, Wanfang data, VIP, SinoMed database, PubMed and the Cochrane Library. The Chinese search keywords were "Tetanus Antitoxin", "Tetanus Antibody", "Healthy Population" and "Mainland China". English search terms include "tetanus antitoxin", "tetanus vaccine", "tetanus vaccine", "general population" and "mainland of China". The time limit for inclusion in literature research was 2010-2019. Stata software was used to conduct meta-analysis on the protection rate of tetanus antibody. Results: A total of 24 articles were included. There was no obvious publication bias in the included articles. The total number of respondents was 23 530, the antibody protection rate was 49.5%-99.0%. A total of 20 817 people got effective antibody protection, which meant the antibody level reached and exceeded 0.1 IU/ml, and the combined protection rate was 78.6% (95%CI: 75.0%-88.2%). The combined protection rates of antibody in 0-7 years old and 8-15 years old groups were 88.9% (95%CI: 86.9%-91.0%) and 79.3% (95%CI: 72.9%-86.2%) respectively. The combined protection rates of antibodies in 16-20 years old, 21-30 years old and 31-40 years old groups were 58.9% (95%CI: 46.5%-71.2%), 47.7% (95%CI: 16.8%-78.7%) and 63.8% (95%CI:32.6%-95.1%) respectively. The combined protection rate of tetanus antibody for 0-15 years old people was 85.6% (95%CI: 83.1%-88.1%), and the combined protection rate of antibody for 16-40 years old people was 52.9% (95%CI: 39.3%-66.6%). Conclusion: With the increase of age, the protection rate of tetanus antibody among the healthy population aged 16-40 years in our country decreases. An individualized vaccination plan should be formulated according to the previous tetanus vaccination history and the tetanus antibody level when necessary.

Band-Resolved Imaging of Photocurrent in a Topological Insulator.

We study the microscopic origins of photocurrent generation in the topological insulator Bi_{2}Se_{3} via time- and angle-resolved photoemission spectroscopy. We image the unoccupied band structure as it evolves following a circularly polarized optical excitation and observe an asymmetric electron population in momentum space, which is the spectroscopic signature of a photocurrent. By analyzing the rise times of the population we identify which occupied and unoccupied electronic states are coupled by the optical excitation. We conclude that photocurrents can only be excited via resonant optical transitions coupling to spin-orbital textured states. Our work provides a microscopic understanding of how to control photocurrents in systems with spin-orbit coupling and broken inversion symmetry.

Differential expression of sonic hedgehog in lung adenocarcinoma and lung squamous cell carcinoma.

Overexpression of Sonic hedgehog (Shh) is associated with progression of several cancers. The expression of Shh in non-small cell lung cancer (NSCLC) has been reported with inconsistent results. Lung adenocarcinoma (LAC) and lung squamous cell carcinoma (LSCC) are two major subtypes of NSCLC, which have different genetic genotypes and clinical therapeutic options. The expression of Shh in specimen of patients with NSCLC has yet to be comprehensively determined according to histological subtypes. Shh expression level was determined in 167 NSCLC patients (56 LAC patients and 111 LSCC patients) by immunohistochemical assay (IHC) and disease-free survival and overall survival of patients were analyzed using the Kaplan-Meier method. Shh protein level in pleural effusion from patients with pneumonia or pleural empyema, tuberculosis, LAC and LSCC was measured with enzyme-linked immunoassay (ELISA). We found that Shh expression is increased in tumor tissues from both LAC and LSCC patients compared with the paired adjacent tissues, while Shh level is negatively correlated with tumor differentiation only in LSCC, LSCC patients containing higher-Shh expression have a poorer prognosis. Furthermore, Shh level is elevated in pleural effusion from LSCC patients compared with that of parapneumonic and LAC pleural effusion. Shh expression in tumor tissues or pleural effusion may represent a potential diagnostic and prognostic marker of LSCC patients, pleural effusion Shh may assist to distinguish between LAC and LSCC.

The Presence and involvement of interleukin-17 in apical periodontitis.

Apical periodontitis (AP) is a chronic inflammatory disease characterized by periapical tissue inflammation and destruction of the associated alveolar bone. It is caused by microbial infections within the root canal and the resultant host immune responses in the periapical tissues. The proinflammatory cytokine interleukin (IL)-17 has been shown to play an important role in many inflammatory diseases. There is increasing evidence of the presence of IL-17 in AP, which might be associated with disease pathogenesis. Moreover, several animal studies indicate the potential role of IL-17 in periapical inflammation and the resultant bone resorption in AP. This article reviews recent studies regarding the collective in vitro, in vivo and clinical evidence of the presence and involvement of IL-17 in AP. A search related to IL-17 in apical periodontitis was conducted on PubMed, EMBASE and Web of Science databases using keywords and controlled vocabulary. Two independent reviewers first screened titles and abstracts and then the full texts that were included. A total of 25 papers were identified, of the 25 included articles, 7 involved laboratory studies on cell cultures, 11 involved animal experimentations, and 7 were observational studies using human clinical samples. In conclusion, evidence for the presence of IL-17 in AP from human and animal models is clear. However, there is relatively little information currently available that would highlight the specific role of IL-17 in AP.

[Clinical experience in the diagnosis and treatment of aortic stenosis caused by Takayasu arteritis in pediatric patients].

Objective: To analyze the clinical features and summarize the experience on the diagnosis and treatment of aortic stenosis caused by Takayasu arteritis in pediatric patients. Methods: This study was a retrospective study. Five pediatric patients diagnosed as aortic stenosis caused by Takayasu arteritis in Fuwai Hospital of Chinese Academy of Medical Sciences from January 2016 to August 2018 were included. The clinical features, methods of examination, treatment and outcome were analyzed. Results: There were 2 male and 3 female patients in this cohort. The age of onset ranged from 10 to 13 years. The main clinical symptoms were as follows: intermittent claudication and hypertension (5 patients), heart failure (3 patients). Three patients with heart failure were misdiagnosed with dilated cardiomyopathy in other hospitals. Except 1 patient died due to disease aggravation before operation, the other 4 patients received interventional therapy for severe heart failure or refractory hypertension on the basis of hormone anti-inflammatory treatment, including 2 patients treated with aortic balloon dilatation and 2 patients treated with aortic balloon dilatation and stent implantation. In post-operational follow-up, clinical symptoms and laboratory examination values of the 4 patients treated with interventional therapy were significantly improved. Conclusions: The clinical symptoms of pediatric patients with aortic stenosis caused by Takayasu arteritis mainly present with intermittent claudication, hypertension and heart failure. Aortic intervention strategy should be applied for pediatric patients with severe heart failure or refractory hypertension as early as possible.

Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300.

Background: There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician's choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC. Patients and methods: Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician's choice of chemotherapy (paclitaxel 80 mg/m2 on days 1, 8, and 15 or irinotecan 150 mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. Results: A total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0 months; hazard ratio (HR)=1.1 [95% confidence interval (CI) 0.9-1.4]; P = 0.81} or the secondary end points of PFS [median, 1.4 versus 2.7 months; HR=1.73 (95% CI 1.4-2.2); P > 0.99] or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm. Conclusions: Treatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy. Trial registration: ClinicalTrials.gov: NCT02625623.

Genetic and clinical findings in a Chinese cohort of patients with collagen VI-related myopathies.

Collagen VI-related myopathy, caused by pathogenic variants in the genes encoding collagen VI, represents a clinical continuum from Ullrich congenital muscular dystrophy (UCMD) to Bethlem myopathy (BM). Clinical data of 60 probands and their family members were collected and muscle biopsies of 26 patients were analyzed. COL6A1, COL6A2 and COL6A3 exons were analyzed by direct sequencing or next generation sequencing (NGS). Sixty patients were characterized by delayed motor milestones, muscle weakness, skin and joint changes with 40 UCMD and 20 BM. Muscle with biopsies revealed dystrophic changes and showed completely deficiency of collagen VI or sarcolemma specific collagen VI deficiency. We identified 62 different pathogenic variants in these 60 patients, with 34 were first reported while 28 were previously known; 72 allelic pathogenic variants in COL6A1 (25/72, 34.7%), COL6A2 (33/72, 45.8%) and COL6A3 (14/72, 19.4%). We also found somatic mosaic variant in the parent of 1 proband by personal genome machine amplicon deep sequencing for mosaicism. Here we provide clinical, histological and genetic evidence of collagen VI-related myopathy in 60 Chinese patients. NGS is a valuable approach for diagnosis and accurate diagnosis provides useful information for genetic counseling of related families.

Tau-mediated iron export prevents ferroptotic damage after ischemic stroke.

Functional failure of tau contributes to age-dependent, iron-mediated neurotoxicity, and as iron accumulates in ischemic stroke tissue, we hypothesized that tau failure may exaggerate ischemia-reperfusion-related toxicity. Indeed, unilateral, transient middle cerebral artery occlusion (MCAO) suppressed hemispheric tau and increased iron levels in young (3-month-old) mice and rats. Wild-type mice were protected by iron-targeted interventions: ceruloplasmin and amyloid precursor protein ectodomain, as well as ferroptosis inhibitors. At this age, tau-knockout mice did not express elevated brain iron and were protected against hemispheric reperfusion injury following MCAO, indicating that tau suppression may prevent ferroptosis. However, the accelerated age-dependent brain iron accumulation that occurs in tau-knockout mice at 12 months of age negated the protective benefit of tau suppression against MCAO-induced focal cerebral ischemia-reperfusion injury. The protective benefit of tau knockout was revived in older mice by iron-targeting interventions. These findings introduce tau-iron interaction as a pleiotropic modulator of ferroptosis and ischemic stroke outcome.

Effects of psychosocial factors on monitoring treatment effect in newly diagnosed rheumatoid arthritis patients over time: response data from the tREACH study.

OBJECTIVES: To investigate whether, apart from effects of patient- and disease-related factors, psychosocial factors have additional effects on disease activity; and which factors are most influential during the first year of treatment in early rheumatoid arthritis (RA). METHOD: The study assessed 15 month follow-up data from patients in tREACH, a randomized clinical trial comparing initial triple disease-modifying anti-rheumatic drug therapy to methotrexate monotherapy, with glucocorticoid bridging in both groups. Patients were evaluated every 3 months and treated to target. Associations between Disease Activity Score (DAS) at 3, 9, and 15 months and psychosocial factors (anxiety, depression, fatigue, and coping with pain) at the previous visit were assessed by multivariable linear regression correcting for demographic, clinical, and treatment-related factors. RESULTS: At 3, 9, and 15 months of follow-up, 265, 251, and 162 patients, respectively, were available for analysis. Baseline anxiety and coping with pain were associated with DAS at 3 months; coping with pain at 6 months was associated with DAS at 9 months, and fatigue at 12 months with DAS at 15 months. Psychosocial factors were moderately correlated. Effects on DAS were mainly due to tender joint count and global health. CONCLUSION: Psychosocial factors have additional effects on DAS throughout the first year of treatment in early RA. A change was observed from anxiety and coping with pain at baseline being associated with subsequent DAS towards fatigue being associated with subsequent DAS at 12 months. Owing to the explorative nature of this study, more research is needed to confirm this pattern.

Experimental study on TGF-ß1-mediated CD147 expression in oral submucous fibrosis.

OBJECTIVE: Although previous evidence indicates that CD147 is closely involved in the progression of organ fibrosis and various signaling pathways have been proven to regulate its expression, the role of CD147 in oral submucous fibrosis (OSF) remains largely unknown. METHODS: In this study, we investigated the expression of CD147 and transforming growth factor ß1 (TGF-ß1) in human samples of an OSF tissue array by immunohistopathology. Pearson's correlation analysis was conducted to explore the correlation between CD147 and TGF-ß1. Immunofluorescence and Western blotting were used to investigate to levels of CD147 in Human Oral Keratinocytes (HOKs) followed by TGF-ß1 or LY2157299, an inhibitor of TGF-ß1 receptor and arecoline stimulation. RESULTS: We found that CD147 was highly expressed in both HOKs and the fibrotic oral mucosa and that this expression was correlated with TGF-ß1 expression. Additionally, CD147 levels were significantly associated with the fibrosis stage. The TGF-ß1 signaling pathway was found to be mainly responsible for CD147 up-regulation after arecoline treatment whereas inhibition of TGF-ß1 down-regulated CD147 expression. CONCLUSION: Our findings suggest arecoline promotes CD147 expression via the TGF-ß1 signaling pathway in HOKs, whereas overexpression of CD147 may promote OSF progression.

Targeting RAD50 increases sensitivity to radiotherapy in colorectal cancer cells.

Radiotherapy resistance remains the major factor limiting the radiotherapy efficacy in colorectal cancer. The Mre11-RAD50-Nbs1 (MRN) complex is known to play a critical role in the DNA double strand breaks (DSBs) repair pathways and thus facilitates radioresistance. Targeting MRN function can sensitize cancer cells to irradiation in some malignancies. In this study, we stably knocked down RAD50 protein in colorectal cancer (CRC) cell lines, HCT116 and DLD1, and evaluated their response to irradiation as well as the DSB repair dynamics. We observed that downregulation of RAD50 sensitized CRC cells to irradiation with reduction in DSB repair efficiency after exposure to irradiation. In addition, RAD50 was found to be upregulated in CRC cancerous tissue samples compared to non-cancerous adjacent tissues (NATs) and in patients who were resistant to RT. Elevated RAD50 expression was associated with poor patient survival in CRC. In conclusion, targeting RAD50 can serve as an efficient strategy to sensitize CRC cells to irradiation. RAD50 protein may be used as a biomarker for patient survival in CRC.

Up-regulation of IL-23 expression in human dental pulp fibroblasts by IL-17 via activation of the NF-κB and MAPK pathways.

AIM: To investigate the effects of the pro-inflammatory and Th17-polarizing mediator IL-17 on HDPFs-mediated IL-23 production and the molecular mechanism involved. METHODOLOGY: Interleukin (IL)-17R expression was determined by semi-quantitative reverse transcriptase-polymerase chain reaction and Western blot in cultured human dental pulp fibroblasts (HDPFs). Quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay were used to determine IL-23 mRNA and protein levels in IL-17-stimulated HDPFs, respectively. The nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) signalling pathways that mediate the IL-17-stimulated production of IL-23 was investigated using Western blot and specific signalling inhibitor analyses. Statistical analyses were performed using Kruskal-Wallis tests followed by the Mann-Whitney U-test. Statistical significance was considered when the P value < 0.05. RESULTS: Primary HDPFs steadily expressed IL-17R mRNA and surface-bound protein. IL-17 stimulated the expression of IL-23 mRNA and protein in cultured human dental pulp fibroblasts, which was attenuated by IL-17 or IL-17R neutralizing antibodies. In accordance with the enhanced expression of IL-23, IL-17 stimulation resulted in rapid activation of p38 MAPK, extracellular signal-regulated kinase (ERK) 1/2, c-Jun-N-terminal kinase (JNK) and NF-κB in HDPFs. Inhibitors of p38 MAPK, ERK 1/2 or NF-κB significantly suppressed, whereas blocking JNK substantially augmented IL-23 production from IL-17-stimulated HDPFs. CONCLUSION: HDPFs expressed IL-17R and responded to IL-17 to produce IL-23 via the activation of the NF-κB and MAPK signalling pathways. The findings provide insights into the cellular mechanisms of the participation of IL-17 in the activation of HDPFs in inflamed pulp tissue.

[Clinical analysis of 138 multiple primary cancers diagnosed of digestive system malignant tumor initially].

Objective: To study the clinical characteristics, strategy of treatment and prognosis of multiple primary cancers(MPC) diagnosed of digestive system malignant tumor firstly. Methods: From January, 2000 to December, 2015, the clinical, follow-up and prognostic data of 138 MPC patients diagnosed of digestive system malignant tumor firstly were retrospectively analyzed. Results: 138 cases were found in 10 580 cases with malignant tumors, and the incidence was 1.30%. There were 129 cases of duplex primary cancers, 8 cases of triple primary cancers and 1 case of quintuple primary cancers. The repetitive primary cancer was occurred in digestive system (61cases, 44.2%) most frequently, with the next in respiratory system (46 cases, 33.3%). 52.2% (72 cases) suffered second primary cancer in 2 years after first primary cancer diagnosed, and 75.4% (104 cases) in 5 years. The median overall survival in patients with all cancer lesions radically treated was 168 months, better than any other treatment (68 months, P<0.05). Conclusions: The second primary cancers of MPC cases initially diagnosed of digestive system malignant tumor most frequently occurred in the digestive system and respiratory system. More concern should be attracted in follow-up, especially in the first 5 years. The key to improve patient' prognosis was radical treatment to every primary cancer.

[A retrospective comparative study of continuous pumping for home enteral nutrition after esophagectomy].

Objective: To discuss the effect and safety of continuous pumping for home enteral nutrition after esophagectomy. Methods: The current study retrospectively analyzed the esophageal cancer patients who underwent transthoracic esophagectomy between January 2017 and November 2017 at First Department of Thoracic Surgery, Peking University Cancer Hospital and Institute. There were totally 108 cases, including 88 males and 20 females, with an average age of 62 years. The patients were divided into pump feeding group (n=56) and traditional tube feeding group (n=52). The postoperative short-term safety, weight maintenance, enteral nutrition tolerance and nutritional support complete rate of the 2 groups were compared by χ(2) test, Fisher exact test and t test, respectively. Results: Compared with traditional tube feeding group, the patient safety in pumping feeding group was significantly better, with complications within 2 months after discharge were 11/52 and 4/56 respectively (χ(2)=2.393, P=0.035); the weight maintenance was significantly better, the weight loss within 4 weeks after discharge were 3.90 kg and 0.13 kg, respectively (t=7.720, P=0.000); the general enteral complications were significantly lower (26/52 vs. 5/56, χ(2)=22.225, P=0.000), the nutritional support complete rate was significantly higher (23/52 vs. 55/56, χ(2)=39.167, P=0.000). Conclusions: Continuous pump feeding enteral nutrition support after discharge postoperatively could help improve patient safety after discharge, which is better for weight maintenance of the patients. Pump feeding could also enhance tolerability of tube feeding and ensure the effective accomplishment of nutritional support.