Presence of Porphyromonas gingivalis in esophagus and its association with the clinicopathological characteristics and survival in patients with esophageal cancer

BACKGROUND: Mounting evidence suggests a causal relationship between specific bacterial infections and the development of certain malignancies. However, the possible role of the keystone periodontal pathogen, Porphyromonas gingivalis, in esophageal squamous cell carcinoma (ESCC) remains unknown. Therefore, we examined the presence of P. gingivalis in esophageal mucosa, and the relationship between P. gingivalis infection and the diagnosis and prognosis of ESCC. METHODS: The presence of P. gingivalis in the esophageal tissues from ESCC patients and normal controls was examined by immunohistochemistry using antibodies targeting whole bacteria and its unique secreted protease, the gingipain Kgp. qRT-PCR was used as a confirmatory approach to detect P. gingivalis 16S rDNA. Clinicopathologic characteristics were collected to analyze the relationship between P. gingivalis infection and development of ESCC. RESULTS: P. gingivalis was detected immunohistochemically in 61 % of cancerous tissues, 12 % of adjacent tissues and was undetected in normal esophageal mucosa. A similar distribution of lysine-specific gingipain, a catalytic endoprotease uniquely secreted by P. gingivalis, and P. gingivalis 16S rDNA was also observed. Moreover, statistic correlations showed P. gingivalis infection was positively associated with multiple clinicopathologic characteristics, including differentiation status, metastasis, and overall survival rate. CONCLUSION: These findings demonstrate for the first time that P. gingivalis infects the epithelium of the esophagus of ESCC patients, establish an association between infection with P. gingivalis and the progression of ESCC, and suggest P. gingivalis infection could be a biomarker for this disease. More importantly, these data, if confirmed, indicate that eradication of a common oral pathogen could potentially contribute to a reduction in the overall ESCC burden. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13027-016-0049-x) contains supplementary material, which is available to authorized users

Optimal allocation of reliability improvement target based on multiple correlation failures and risk uncertainty

Optimal allocation of the reliability improvement target is essential for the system optimization design. In order to solve the problems that the optimization model is with loss of generality and the validity of the optimal solution is weakened, an optimal allocation method is proposed by considering multiple correlation failures and risk uncertainty in this paper. Two new concepts are presented, such as independent failure results in basic risk, and correlation failure leads to disturbance risk. A risk assessment machinery of “actual risk = basic risk + disturbance risk” is proposed. The action mechanisms of the three correlation failures are studied based on the cooperation game theory, and the generalized risk models are given under probability measure. Considering the improvement cost, the expectation and the variance of the reduction of system risk, a multi-objective optimal allocation model is developed, which is solved by using the PSO algorithm. Finally, the proposed optimal allocation is implemented at the 2-stage NGW planetary reducer, and the results show that it is more efficient and feasible for engineering practice

RELIABILITY ALLOCATION OF PLANETARY REDUCER BASED ON ADVANCED INTEGRATED FACTORS ALLOCATION METHOD (MT)

The service life of the planetary reducer in a hub drive system largely depends on the system reliability design. Aimed at the problems of lower credibility and inadequate depth in the reliability allocation, based on improved FMECA formulas and order statistics theory, an advanced reliability allocation method of the planetary reducer is proposed. The basic characteristics of the planetary reducer are analyzed, and FMECA formulas with the positive failure correlation modifying operator are presented, which indicate that the subsystem complexity and the failure occurrence change in the same direction as the failure correlation degree, respectively. Simultaneously, based on the Gumbel Copula function and order statistics theory, the reliability allocation model is established to assign reliability design indices to parts of the planetary reducer. By comparing the subsystem reliability allocation weights obtained by different methods, results show that the allocation result of the proposed method is more credible. It will be helpful to accomplish the deeper reliability allocation and improve the service life of the planetary reducer

HOPE-SIM, a cryo-structured illumination fluorescence microscopy system for accurately targeted cryo-electron tomography

Abstract Cryo-focused ion beam (cryo-FIB) milling technology has been developed for the fabrication of cryo-lamella of frozen native specimens for study by in situ cryo-electron tomography (cryo-ET). However, the precision of the target of interest is still one of the major bottlenecks limiting application. Here, we have developed a cryo-correlative light and electron microscopy (cryo-CLEM) system named HOPE-SIM by incorporating a 3D structured illumination fluorescence microscopy (SIM) system and an upgraded high-vacuum stage to achieve efficiently targeted cryo-FIB. With the 3D super resolution of cryo-SIM as well as our cryo-CLEM software, 3D-View, the correlation precision of targeting region of interest can reach to 110 nm enough for the subsequent cryo-lamella fabrication. We have successfully utilized the HOPE-SIM system to prepare cryo-lamellae targeting mitochondria, centrosomes of HeLa cells and herpesvirus assembly compartment of infected BHK-21 cells, which suggests the high potency of the HOPE-SIM system for future in situ cryo-ET workflows

Chemoradiation versus oesophagectomy for locally advanced oesophageal cancer in Chinese patients: study protocol for a randomised controlled trial

Abstract Background Surgery is the gold standard treatment for local advanced disease, while definitive concurrent chemoradiotherapy (DCRT) is recommended for those who are medically unable to tolerate major surgery or medically fit patients who decline surgery. The primary aim of this trial is to compare the outcomes in Chinese patients with oesophageal squamous cell cancer with locally advanced resectable disease who have received either surgery or DCRT. Methods/design One hundred ninety-six patients with T1bN + M0 or T2-4aN0-2 M0 oesophageal squamous cell cancer will be randomised to the DCRT group or the surgery group. In the DCRT group, patients will be given intensity-modulated radiation therapy (IMRT) with 50 Gy/25 fractions and basic chemotherapy with 5-fluorouracil regimens. In the surgery group, patients will receive neoadjuvant chemoradiotherapy (NCRT) and standard oesophagectomy. Five years of follow-up will be scheduled for patients. The primary endpoints are 2-year/5-year overall survival; the secondary endpoints are 2-year/5-year progression-free survival, treatment-related adverse events and the patients’ quality of life. The main evaluation methods include oesophagoscopy, endoscopic ultrasonography and biopsy, oesophageal barium meal, computed tomography, positron emission tomography-computed tomography, blood tests and questionnaires. Discussion The preponderant oesophageal cancer pathology type is dramatically different in western Caucasian and Asian oesophageal cancer patients: Caucasian patients present with 80% adenocarcinomas, and Asians patients present with 95% squamous cell carcinomas. This phenomenon needs more in-depth studies to elucidate the differences in these populations. Based on the results of this study, we will show whether DCRT will benefit patients more than oesophagectomy. This study will contribute more evidence to the management of oesophageal squamous cell cancer. Trial registration ClinicalTrials.gov, NCT02972372. Registered on 26 November 2016

Additional file 2: Table S1. of Presence of Porphyromonas gingivalis in esophagus and its association with the clinicopathological characteristics and survival in patients with esophageal cancer

Concordance between the immunohistochemistry of P. gingivalis whole antigens and RT-PCR of P. gingivalis 16S rRNA in the cancerous tissue from patients with ESCC. (PDF 43 kb

Additional file 1: Figure S1. of Presence of Porphyromonas gingivalis in esophagus and its association with the clinicopathological characteristics and survival in patients with esophageal cancer

P. gingivalis 16S DNA in esophageal epithelium. PCR with specific primers for P. gingivalis (upper), and a universal primer (lower). Representative images of P. gingivalis PCR products from several pairs of cancerous (lanes 2, 4, 6, 8) and adjacent fresh biopsy tissues from ESCC patients (lanes 3, 5, 7, 9), and normal biopsy tissues as a control (Lane 10). Lanes1 and 11 are molecular size markers. (PDF 215 kb