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Our paper aims at learning from imbalance data based on ensemble learning. At the stage, the main solution is to combine under-sampling, oversampling or cost sensitivity learning with ensemble learning. However, these feature space-based methods fail to reflect the transformation of distribution and are usually accompanied with high computational complexity and risk of overfitting. In this paper, we propose a dynamic cluster algorithm based on coefficient of variation (or entropy), which learns the local spatial distribution of data and hierarchically clusters the majority. This algorithm has low complexity and can dynamically adjust the cluster according to the iteration of AdaBoost, adaptively synchronized with changes caused by sample weight changes. Then, we design an index to measure the importance of each cluster. Based on this index, a dynamic sampling algorithm based on maximum weight is proposed. The effectiveness of the sampling algorithm is proved by visual experiments. Finally, we propose a cost-sensitive algorithm based on Bagging, and combine it with the dynamic sampling algorithm to propose a multi-fusion imbalanced ensemble learning algorithm. In experimental research, our algorithms have been validated on three artificial datasets, 22 KEEL datasets and two gene expression cancer datasets, and have shown ideal or better performance than SOTA in terms of AUC, indicating that our algorithms are not only effective imbalance algorithms, but also provide potential for building a reliable biological cyber-physical system.

Atherosclerotic plaque rupture is the main cause of many cardiovascular diseases, and biomechanical factors play an important role in the process of plaque rupture. In the study of plaque biomechanics, there are relatively few studies based on fatigue fracture failure theory, and most of them mainly focus on the whole fatigue propagation process from crack initiation to plaque rupture, while there are few studies on the influence of crack on plaque rupture at a certain time in the process of fatigue propagation. In this paper, a two-dimensional plaque model with crack was established. Based on the theory of fracture mechanics and combined with the finite element numerical simulation method, the stress intensity factor (SIF) and related influencing factors at the crack tip in the plaque were studied. The SIF was used to measure the influence of crack on plaque rupture. The results show that the existence of crack can lead to local stress concentration, which increases the risk of plaque rupture. The SIF at the crack tip in the plaque was positively correlated with blood pressure, but negatively correlated with fibrous cap thickness and lipid pool stiffness. The effect of the thickness and angle of lipid pool on the SIF at the crack tip in the plaque was less than 4%, which could be ignored. This study provides a theoretical basis for the risk assessment of plaque rupture with cracks.动脉粥样硬化斑块破裂是引发众多心血管疾病的主要原因，而生物力学因素在斑块破裂过程中有着重要的作用。在斑块生物力学的研究中，基于疲劳断裂破坏理论的研究相对较少，而且大部分相关研究主要关注的是裂纹从萌生直至斑块破裂的整个疲劳扩展过程，而对疲劳扩展过程中某一时刻下裂纹对斑块破裂的影响的研究较少。本文针对这个问题建立了二维含裂纹的斑块模型，基于断裂力学理论并结合有限元数值模拟方法研究了斑块中裂纹尖端的应力强度因子（SIF）及相关影响因素，通过SIF来衡量裂纹对斑块破裂的影响程度。结果表明，裂纹的存在会引发局部应力集中进而增大斑块破裂风险。斑块裂尖SIF与血压呈线性正相关，而与纤维帽厚度和脂质池刚度呈负相关。脂质池厚度和角度对斑块裂尖SIF的影响均低于4%，可以忽略不计。本研究为含裂纹斑块的破裂风险评估提供了一定的理论依据。.

The long noncoding RNA (lncRNA) H19 has been described to participate in the metastasis of various tumors. Nevertheless, whether H19 promotes or impedes tongue squamous cell carcinoma (TSCC) cell migration and invasion remains controversial. Here we found that the expression of H19 was elevated in TSCC tissues compared with adjacent normal tissues. Moreover, we demonstrated that the expression of H19 was higher in metastasized tumors compared with unmetastasized tumors. Consistently, TSCC cells express higher levels of H19 than human squamous cells. Subsequently, depletion of H19 impaired the migration and invasion abilities of TSCC cells. Mechanistically, we demonstrated that H19 functions as a competing endogenous RNA (ceRNA) to sponge miRNA let-7a, leading to an increase in a let-7a target, the key regulator of tumor metastasis HMGA2, which is enriched in TSCC tissues and cell lines. Intriguingly, inhibition of let-7a significantly rescued the short hairpin H19 (shH19)-induced decrease in TSCC migration and invasion. These findings revealed that the H19/let-7a/HMGA2/EMT axis plays a critical role in the regulation of TSCC migration and invasion, which may provide a new therapeutic target for TSCC.

Joint clearance and gravitational effects are considered and their coupling effects on the dynamic performance of open loop mechanisms are modeled. A continuous dissipative Hertz contact model is applied to describe the contact phenomenon in the joint and the friction force is calculated using the modified Coulomb’s friction law. The dynamic behaviors of open loop mechanisms under different combinations of clearance joints location and body masses are numerically modeled. The results show that the location of the clearance joints and the body gravity are important factors to dynamic behavior of the open loop mechanisms. The closer to the end-effector, the stronger influence on the system. The errors induced by multiple joints with clearance can be transmitted and accumulated. The component of gravity varies unevenly has an extremely strong effect the on dynamics of the open-loop topology, the farer body owns heavier weight to the end-effector, the stronger influence on the system. The results may provide a theoretical basis and technical support for the design the open loop mechanisms.

Variable compliance mechanisms are considered as an effective way for interaction with changeable environments. Existing designs of variable compliance mechanisms can only change the amplitude of compliance rather than the orientation of compliance. In this paper, a novel hybrid mechanism is designed to realize changeable compliance orientation in a large range. The mechanical structure and working principle of the designed mechanism are firstly presented. Then, the closed-form relationship between compliance orientation and configuration of the designed mechanism is analyzed. Spherical coordinates are used to characterize and evaluate the orientation of compliance. Theoretical analysis shows that the orientation of compliance can be changed in a large range spatially. Finite element analysis is also performed to verify the theoretical model. It shows that the orientations of deformation during simulations are close to the theoretical compliance orientations. Under unchanged loading conditions, a large change in deformation orientation can be achieved by changing the mechanism’s configuration. This indicates that the designed mechanism can change the compliance orientation in a large range.

The horizontal displacement values experienced by the isolation layer of base-isolated buildings can exceed the allowable range and cause failures during the rare or very-rare earthquakes. Excessive horizontal displacements of the isolation layer may cause collisions between the building and retaining walls of the isolation ditch and even cause the collapse of the isolated building. This paper proposes a cost-effective, easy-to-build, passive bumper device, called Flexible Limit Protective Device (FLPD) in order to act as shock-absorbers. Through numerical simulations and experiments, the nonlinear behavior of the FLPD is investigated. Subsequently, through structural simulations, the effectiveness of using FLPDs is studied. The elitist non-dominated sorting genetic algorithm (NSGA-II) is used to optimize the design of FLPDs, and the response of structures equipped with optimized FLPDs are simulated numerically. The results indicate that proposed optimized FLPDs can effectively work as shock-absorbers for base-isolated structures. This paper can provide a guideline for the design of shock-absorbers.

Background and Objective While osseointegration following various dental implant placement protocols has been extensively investigated, the neurohistological integration has received little attention. The primary aim of this study was to compare the myelinated nerve fibers density in peri-implant bone tissue following various implant placement protocols. The secondary aim assessed the effect of follow-up on peri-implant nerve fibers density. Methods Ten beagle dogs randomly received 68 commercially pure titanium implants in the mandibular premolar or molar region bilaterally following extraction utilizing one of the six treatment protocols: (a) immediate implant placement (IIP) and immediate loading (IL); (b) IIP and delayed loading (DL); (c) IIP and left unloaded (UL); (d) delayed implant placement (DIP) and IL; (e) DIP and DL; and (f) DIP and UL. Histomorphometric analysis of the peri-implant myelinated nerve fibers was performed in a 300 mu m peri-implant zone at the cervical, middle, and apical level following implant placement. The follow-up assessment involved longitudinal observation at 3 months following each implant treatment protocol and at 6 months for IIP+IL and IIP+DL protocols. Results The influence of different treatment protocols, including the fixed effects of implant groups (IIP+IL, IIP+DL, IIP+UL, DIP+IL, DIP+DL, DIP+UL) and regions (cervical, middle, apical), was examined via a linear mixed model. The IIP+IL group showed a significantly higher myelinated nerve density compared to the IIP+UL and DIP+UL group. Peri-implant nerve re-innervation was significantly higher (P = .002) in the apical region compared to the cervical region. After immediate implant placement, the IL group showed a significantly (P = .03) higher density of myelinated nerve fibers compared to DL. No significant (P = .19) effect of follow-up on nerve density was observed. Conclusion The immediate implant placement and loading protocol showed most beneficial effect on peri-implant innervation with highest myelinated nerve density in the apical region. A longer loading time had no influence on the peri-implant nerve density. China Scholarship CouncilChina Scholarship Council [201708210187] Funding Source: Medline; Fonds Wetenschappelijk Onderzoek FWO[11.ZU.117N] Funding Source: Medline; National Natural Science [81370026] Funding Source: Medline Jacobs, R (corresponding author), Katholieke Univ Leuven, Dept Imaging & Pathol, OMFS IMPATH Res Grp, Campus Sint Rafael,Kapucijnenvoer 33, BE-3000 Leuven, Belgium. reinhilde.jacobs@kuleuven.be

Background The incidence and mortality rate of colorectal cancer (CRC) have increased dramatically over the past 3 decades in China due to changes in lifestyle factors. Early detection and treatment guidelines for asymptomatic cases have shown to improve CRC control in developed countries. In response to these challenges, the Shanghai Municipal Government launched a community-based CRC screening program in 2012. Materials and Methods Free initial screening, inclusive of immunochemical fecal occult blood and risk assessment (questionnaire), was provided by community health centers in Shanghai. Participants with positive results were referred to a specialist for a colonoscopy. Results In 2013, 828,302 Shanghai residents were registered; 97.7% (809,528) of the registrants completed initial screening. Among 180,094 initial screening-positive participants, 71,733 underwent colonoscopy. The proportion of compliance to colonoscopy was 39.8%; the proportion decreased with age and educational level. A total of 6,668 adenomas were detected, and 1,630 CRC cases were diagnosed. The CRC detection rate of the program was 201.35/100,000; among the detected CRCs, 51.6% were in stage 0–I. Conclusion The screening program achieved great progress, especially on initial screening completion and CRC early stage rate, although particular intervention is still needed to improve the compliance of colonoscopy. Implications for Practice Due to socioeconomic transitions and lifestyle changes, colorectal cancer is now becoming one of the most common cancers in developing countries, as it is in developed countries. While most developed countries have now initiated national colorectal cancer screening programs based on recommended country-specific colorectal cancer screening guidelines, colonoscopy has become the most commonly used screening method. This is a challenge in developing countries due to limited resources. Based on the analysis of the Shanghai colorectal cancer screening program, with immunological fecal occult blood test and risk assessment as initial screening, followed by a diagnostic testing of colonoscopy for individuals with positive results, this article provides the basis and suggestion for similar program in other regions of China and other developing countries.

We evaluated the effects of Bio-Oss® (a natural bone substitute derived from the mineral portion of bovine bone) on delayed osseointegration of implants. The bilateral third and fourth mandibular premolars of 4 adult, healthy, male and female dogs were extracted. We randomly selected 2 extraction sockets in each dog to be filled with Bio-Oss® (the experimental group); the other 2 extraction sockets, which were not treated, served as controls. Dental implants were inserted into the alveolar bone of the experimental group and the control group 3 months after insertion of the Bio-Oss®. The osteogenic activity in the bone around the implants was assessed by evaluating the histological morphology and estimating histomorphometric variables at 3 and 6 months after delayed implantation. After 3 months, Goldner's trichrome staining analysis showed that the rate of content between the bone and the implant and the mineralised area of bone around the implant were significantly higher in the experimental group (76%(9%) and 69.5% (9.6%), respectively) than those in the control group (56.1% (8.2%) and 52.8% (7.3%), respectively, p=0.003 and 0.000). However, the 2 groups did not differ significantly at 6 months. Fluorescence microscopy showed that the mean rates of mineralisation of the bony tissue around the implant in the experimental group at months 3 and 6 were 6.8 (0.4) μm and 8.4 (0.8) μm, respectively, which were significantly higher than those in the control group (p=0.000 and 0.03). These data indicate that putting Bio-Oss® into the extraction sockets can promote osseointegration after delayed implantation, and may be a promising option for clinical use.

Although neurophysiological and psychophysical proof of osseoperception is accumulating, histomorphometric evidence for the neural mechanisms of functional compensation following immediate and delayed implant loading is still lacking. For this randomized split-mouth study, six mongrel dogs randomly received one of four treatment protocols at 36 implant-recipient sites over 16 weeks (third maxillary incisor, third and fourth mandibular premolar): immediate implant placement and immediate loading (IIP+IL); delayed implant placement and delayed loading (DIP+DL); delayed implant placement and immediate loading (DIP+IL); and natural extraction socket healing (control). Histomorphometry was performed in the peri-implant bone and soft tissues within 300 µm around the implants. Immunocytochemistry and transmission electron microscopy were used to confirm the presence of neural structures and to reveal their ultrastructural characteristics, respectively. Myelinated nerve fibres densely populated the peri-implant crestal gingival and apical regions, although they were also identified in the woven bone and in the osteons near the implant threads. Compared with the control group in the mandible, the group that received IIP+IL showed a higher innervation (in N⋅mm−2, 5.94±1.12 vs. 3.15±0.63, P

Purpose To develop a method for characterizing trabecular bone microarchitecture using cone beam computed tomography (CBCT) and to evaluate trabecular bone changes after rehabilitation using immediate versus delayed implant protocols. Materials and Methods Six mongrel dogs randomly received 27 titanium implants in the maxillary incisor or mandibular premolar areas, following one of four protocols: (1) normal extraction socket healing; (2) immediate implant placement and immediate loading; (3) delayed implant placement and delayed loading; (4) delayed implant placement and immediate loading. The animals were euthanized at 8 weeks, and block biopsies were scanned using high resolution CBCT. Standard bone structural variables were assessed in coronal, middle, and apical levels. Results Coronal and middle regions had more compact, more platelike, and thicker trabeculae. Protocols (2), (3), and (4) had significantly higher values (p

Background To provide a comprehensive overview of temporal trends in cancer incidence during 1973–2010 in urban Shanghai. Methods The estimated annual percent changes (EAPCs) for the whole period and for the time segments in age-standardized incidence rates (ASR) were evaluated with Joinpoint analysis. Age-period-cohort (APC) models were modeled to examine the effects of age, period and birth cohort on cancer incidence. Results The overall ASR decreased slightly and significantly in males (EAPC of −0.41) but increased significantly in females (EAPC of 0.57) during 1973–2010 in urban Shanghai. The incidence trend was not linear and varied by time segments. During the most recent 10 years (2001–2010), the ASR in males decreased by 1.65 % per year and stabilized in females. Incidence rates continued to decline during 1973–2010 for esophagus, stomach, and liver cancer in both sexes, as well as male lung cancer and cervix cancer. It should be noted that it was the first time to document a significant decline in lung cancer incidence among males during 1973–2010 with EAPC of −0.58 %, and a notable upward for cervix cancer since 1996 with EAPC of 8.94 %. Unfavorable trends in incidence were observed for the most common cancer sites in the 38 years period: colorectum, gallbladder & biliary tract, pancreas, kidney, bladder, brain & central nervous system (CNS), thyroid, non-Hodgkin’s lymphoma (NHL), prostate, female breast, corpus uteri, and ovary. APC analysis showed age, period and birth cohort yielded different effects by cancer sites. Conclusions The observed trends primarily reflect dramatic changes in socioeconomic development and lifestyles in urban Shanghai over the past four decades.

To understand the incidence trend of malignant tumors in children aged15 years in Shanghai.The15 years old children diagnosed with cancer in Shanghai between 2009 and 2011 were included in this study. The types of malignant tumors were classified according to International Classification of Childhood Cancer, Version 3 (ICCC-3). The gender and age specific incidences of malignant tumors were analyzed. Software Joinpoint was used to calculate the annual percentage of childhood cancer cases.A total of 460 cases of childhood cancer were diagnosed in Shanghai during 2009-2011, accounting for 0.3% of total cancer cases. The crude incidence was 129.0 per million and the age standardized rate (ASR) was 129.6 per million. The ASR was higher in boys (142.1 per million) than in girls (116.4 per million). The boy to girl ratio was 1.2(95%CI: 1.0-1.5). The incidence was highest in age group5 years (165.1 per million). The incidences in age groups 5-9 years and 10-14 years were 101.2 per million and 113.9 per million, respectively. Leukemia was the most common cancer in children (n=165, 35.9%, ASR: 47.0 per million), followed by central nervous system tumors (n=91, 19.8%, ASR: 25.6 per million) and lymphomas (n=45, 9.8%, ASR: 12.6 per million). The age and gender specific incidence of malignant tumors and the type specific incidence of malignant tumors in children in Shanghai had no significant changes during the study period.The incidence of malignant tumors was higher in boys than in girls in Shanghai. Leukemia, central nervous system tumors and lymphomas were the three most common cancers in children. The overall incidence of malignant tumors in children in Shanghai had no significant changes during 2002-2011.

In the present study, we investigated the effects of manganese chloride (MnCl2) on cell cycle progression in A549 cells used as a model of Mn-induced lung toxicity. Cells were treated with various concentrations of MnCl2 (0, 0.01, 0.1, 0.5, 1.0 or 2.0 mM) for 24, 48 or 72 h. Cell proliferation was determined with MTT assay and mitotic index measurement and apoptosis was measured by flow cytometer. The results showed that MnCl2 inhibited A549 cells proliferation in a dose- and time-dependent manner, and induced apoptosis in A549 cells. When G0/G1 cells obtained by serum starvation were incubated with 0.5 mM of MnCl2 in the presence of 10% serum for several time intervals, the disruption of cell cycle progression was observed. The G0/G1 arrest was induced by MnCl2 treatment at 16 h and the arrest maintained for 8 h. Following the G0/G1 arrest, MnCl2 blocked the cells at S phase at 28 h and the S phase arrest maintained for at least 4 h. And moreover, proteasome inhibitor MG132 was able to prolong the duration of G0/G1 arrest induced by MnCl2 treatment. Results of western blotting assay revealed that cellular Cdk4, Cdk2 and phospho-Cdk2 (Thr160) levels decreased in manganese-treated cells at both 20 and 28 h. In addition, the decreasing of Cyclin A level and the increasing of p53 and WAF1/p21 were also induced by MnCl2 treatment at 20 h. The expression of Cyclin D1, Cyclin E and Cdc25A proteins was not altered in manganese-treated cells at both 20 and 28 h. Our results indicate that MnCl2 orderly induces G0/G1 and S phase arrest in A549 cells, the decreasing of Cdk4, Cdk2 and Cyclin A, and the increasing of p53 and Cdks inhibitor WAF1/p21 might be responsible for the G0/G1 arrest, and the decreasing of Cdk4 and Cdk2 levels for the S phase arrest.

Objective; The present investigation was designed to evaluate the regenerating effects of chip bone grafts harvested from implant drilling and biomaterials with or without combined application of guided bone regeneration (GBR) for the augmentation of peri-implant bone defects. Materials and methods; Four mongrel dogs were used. After the mandibular premolars were extracted for 12 weeks, surgical implantation of 4 titanium implants was performed on each side of the mandible. Chip bone was collected during the drilling procedure. Three-wall bone defects, about 2 mm high, 2 mm wide, and 3 mm long, were created at the buccal side of each implant. The osteotomy sites were separately filled with autogenous chip bone, Bio-oss mineral bone or mixture of both except one defect was left empty. The operation areas of the left mandibula were covered with titanium membranes. The right mandibles without membrane were used as controls. The dogs were sacrificed at either 9 or 16 weeks after the second operation. After the specimens containing experimental implants were resected, the resorption amount of the bone graft was measured. Then the specimens were processed for ground sectioning. The sections were stained with methylene blue and alkalescence fuchsin. Histological examination was performed and photographs were taken under photomicroscope. Results; The mean vertical distances of each bone defects were 2.64±0.17 mm in the D1 (control) group, 1.81± 0.21 mm in D2 (autograft) group, 1.72±0.34 mm in D3 (Bio-oss) group, 1.51±0.22 mm in D4 (mixture) group. Statistical analysis demonstrated that there was significant difference between the results of D1 and the results of other three groups (p

The exposing of dental implant into the maxillary sinus combined with membrane perforation might increase risks of implant failure and sinus complications. Objective: The purpose of this study was to investigate the effects of the dental implant penetration into the maxillary sinus cavity in different depths on osseointegration and sinus health in a dog model. Material and Methods: Sixteen titanium implants were placed in the bilateral maxillary molar areas of eight adult mongrel dogs, which were randomly divided into four groups according to the different penetrating extents of implants into the sinus cavities (group A: 0 mm; group B: 1 mm; group C: 2 mm; group D: 3 mm). The block biopsies were harvested five months after surgery and evaluated by radiographic observation and histological analysis. Results: No signs of inflammatory reactions were observed in any maxillary sinus of the eight dogs. The tips of the implants with penetrating depth of 1 mm and 2 mm were found to be fully covered with newly formed membrane and partially with new bone. The tips of the implants with penetrating depth over 3 mm were exposed in the sinus cavity and showed no membrane or bone coverage. No significant differences were found among groups regarding implant stability, bone-to-implant contact (BIC) and bone area in the implant threads (BA). Conclusions: Despite the protrusion extents, penetration of dental implant into the maxillary sinus with membrane perforation does not compromise the sinus health and the implant osseointegration in canine.

Background Glycosylated hemoglobin A1c (HbA1c) has been applied to identify type 2 diabetes (T2DM) in the U.S. and European countries. It has not been used in China mainly due to lack of a standardized approach to measure HbA1c, short of knowledge about racial-specific standard and deficiency of an optimal cut-off point. Methods To evaluate combination of HbA1c and fasting plasma glucose (FPG) in diagnosing T2DM in Chinese adults, a multistage sampling cross-sectional study was conducted in Shanghai, China, in 2009. The FPG measurement, HbA1c assay, and oral glucose tolerance test (OGTT) were performed in 6,661 Chinese adults (3057 men, 3604 women) who had no prior history of diabetes to identify the unrecognized T2DM. Results A total of 454 participants were identified as T2DM based on the 1999 World Health Organization (WHO) diagnostic criteria. Of these patients, 239 were detected using an FPG ≥ 7.0 mmol/l and 141 were further identified using an HbA1c ≥ 43 mmol/mol (6.1%), achieving a sensitivity of 83.7% and a specificity of 89.3% for combining use of FPG and HbA1c. In subjects at high risk of diabetes, the combining use of FPG and HbA1c produced a higher sensitivity and an improved positive predictive value (PPV), and had a satisfactory specificity and negative predictive value (NPV). Conclusions The combining use of FPG and HbA1c is a potential screening and diagnosis approach for T2DM in Chinese adults, especially among those at high risk of the disease.

To develop a method for characterizing trabecular bone microarchitecture using cone beam computed tomography (CBCT) and to evaluate trabecular bone changes after rehabilitation using immediate versus delayed implant protocols.Six mongrel dogs randomly received 27 titanium implants in the maxillary incisor or mandibular premolar areas, following one of four protocols: (1) normal extraction socket healing; (2) immediate implant placement and immediate loading; (3) delayed implant placement and delayed loading; (4) delayed implant placement and immediate loading. The animals were euthanized at 8 weeks, and block biopsies were scanned using high resolution CBCT. Standard bone structural variables were assessed in coronal, middle, and apical levels.Coronal and middle regions had more compact, more platelike, and thicker trabeculae. Protocols (2), (3), and (4) had significantly higher values (p0.001) than protocol (1) for bone surface density, bone surface volume ratio, and connectivity density, while significantly lower values (p0.001) were found for trabecular separation and fractal dimension. However, protocols (2), (3), and (4) did not show significantly different bone remodeling.Compared with normal extraction healing, the implant protocols have an improved bone structural integration. Results do not suggest a different bone remodeling pattern when a delayed versus an immediate implant protocol is used.

Aim The aim was to investigate the association between human insulin and cancer incidence and mortality in Chinese patients with type 2 diabetes. Methods We recruited 8,774 insulin-naïve diabetes patients from the Shanghai Diabetes Registry (SDR). The follow-up rate was 85.4%. All subjects were divided into the insulin use cohort (n = 3,639) and the non-insulin use cohort (n = 5,135). The primary outcome was the first diagnosis of any cancer. The secondary outcome was all-cause mortality. Cox proportional hazards model was used to estimate the relative risk (RR) of cancer and mortality. Results We observed 98 cancer events in the insulin use cohort and 170 in the non-insulin use cohort. Cancer incidence rates were 78.6 and 74.3 per 10,000 patients per year in the insulin users and the non-insulin users, respectively. No significant difference in cancer risk was observed between the two cohorts (adjusted RR = 1.20, 95% CI 0.89–1.62, P = 0.228). Regarding site-specific cancers, only the risk of liver cancer was significantly higher in the insulin users compared to that in the non-insulin users (adjusted RR = 2.84, 95% CI 1.12–7.17, P = 0.028). The risks of overall mortality (adjusted RR = 1.89, 95% CI 1.47–2.43, P, published_or_final_version

Background: Evidence from epidemiologic investigation indicates that people with type 2 diabetes (T2DM) are at a significantly higher risk of many types of cancer and mortality. The aim of this study was to investigate the incidence and mortality risks of cancer in patients with T2DM compared with the general population in Shanghai, China. Methods: Based on the Shanghai Diabetes Registry (SDR) database linking to the Shanghai Cancer Registry and Surveillance System (SCRSS), a total of 12,276 T2DM patients without cancer were defined and followed up from 1 December 2001 to 31 July 2011. Standardized incidence ratio (SIR) and standardized mortality ratio (SMR) with 95% confidence interval (CI) were calculated using the whole gender and age-matched general population of Shanghai as a reference during the same period. Results: The overall cancer risk was found higher in both males and females T2DM patients, with the SIR of 3.14 (95% CI 2.73–3.56) and 4.29 (95% CI 3.64–4.94), respectively. The overall mortality risk of cancer also significantly increased with the SMR of 2.27 (95% CI 1.86–2.68) and 1.86 (95% CI 1.46–2.26), respectively. Pancreatic cancer was with the highest SIR and SMR in both genders. Conclusions: Compared with the general population, patients with T2DM were associated with higher incidence and mortality risks of cancer, especially pancreatic cancer.

To study the effect of sucrose on glucose and lipid metabolism and the pathological changes in liver and pancreas of diabetic and normal rats.32 Wistar rats and 32 GK rats were randomly divided into W (Wistar), WS (Wistar + 30% sucrose), G (GK) and GS (GK +30% sucrose ) groups. There was 30% sucrose in the drinking water for WS and GS groups and no sucrose in the drinking water for W and G groups. The metabolism of glucose and lipid and the pathological changes of liver and pancreas were observed at the 2nd, 4th, 6th and 10th week of the experiment respectively.The body weight and serum TG of WS group increased gradually after drinking water with sucrose, while serum Glu and TC were not changed. There were some pathological lesions in the liver and pancreas of WS group, and the occurrence of lesions in pancreas was earlier than that in liver. Besides what discovered in WS group, serum TC of GS group decreased initially and then gradually recovered, while serum Glu decreased initially then gradually increased. In comparison with WS group, the occurrence of pancreas and liver injuries in GS group was earlier and severer than those in WS group.Sucrose is harmful for GK and Wistar rats, and could induce or exacerbate the disorder of glucose and lipid metabolism, the pathological lesions of liver and pancreas, and showed a time-response relationship.

In the present study, we investigated the proteomic profiling of anti-benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (anti-BPDE)-transformed human bronchial epithelial cell line (16HBE-C) and its parental cell line (16HBE) G0/G1 cells. Differential analysis of proteomic profiling indicated that 67 polypeptides were down-regulated and 77 polypeptides were up-regulated in 16HBE-C G0/G1 cells compared to 16HBE G0/G1 cells. Then 16 differentially expressed protein spots were analyzed with Q-TOF MS/MS. Of these spots, 3 down-regulated polypeptides were identified as sorcin, small ubiquitin-related modifier 2 precursor and eukaryotic translation initiation factor 5A-1, and 9 up-regulated polypeptides were identified as calmodulin, myosin light polypeptide 6, eukaryotic translation initiation factor 6, proliferating cell nuclear antigen (PCNA), tumor protein D52 (TPD52), superoxide dismutase [Cu-Zn], prohibitin, nuclear protein Hcc-1 and vimentin. These proteins are involved in cell proliferation, protein synthesis, signal transduction and carcinogenesis. Western blotting analysis verified the increased expression levels of PCNA and TPD52 in 16HBE-C G0/G1 cells. Based on the clues from proteomic analysis, the migration and invasion capabilities of 16HBE-C and 16HBE cells were tested. The results indicated that 16HBE-C cells showed much higher migration and invasion capabilities than 16HBE cells, and moreover, the suppression of TPD52 by RNAi resulted in significant decrease of migration and invasion capabilities of 16HBE-C cells. These results will be valuable for further investigating and understanding the mechanisms underlying BaP-induced carcinogenesis.

To study the interaction of beta-carotene on lipid peroxidation induced by the smoke of cigarette.Rat type II pneumocytes were isolated, cultured and then exposed to particles extracted from cigarette smoke and/or beta-carotene for 24 h. Malondialdehyde (MDA) in the cells was measured by TBA method. On the other hand, serum MDA of mice given beta-carotene supplements and/or exposed to cigarette smoke for 10 days was measured.The particles extracted from cigarette smoke increased the content of MDA in the rate type II pneumocytes, and the lipid peroxidation was antagonized by adding 0.5 microgram/ml of beta-carotene to the cells simultaneously. The results from the in vivo study showed that serum MDA levels were increased in the cigarette smoke-treated groups, and the lipid peroxidation was reduced by treating mice with 2.5 mg per kg body weight of beta-carotene.beta-carotene had an antagonistic effect on lipid peroxidation induced by cigarette smoke. The effective dosage of beta-carotene was 0.5 microgram/ml for rat pneumocytes and 2.5 mg/kg BW weight for mice.

Cancer is the culmination of the chronic disease process, and can be attributed the interactions of environment and genes. An optimistic message for 35% cancer prevention may be in dietary constituents, food supply. Carotenoids are isoprenoid compounds synthesized in plants and microorganisms, but not in animals. Human tissue contains only a fraction of the total number of carotenoids(nearly 600 have been identified in nature) present in food supply such as fruit and vegetables. People with high intake of beta-Carotene have a reduced risk of cancer. This outcome seems to bear relation to the chemical to quench singlet oxygen and inhibit peroxyl free radical reaction. But the ATBC and CARET cancer prevention study found the increase in lung cancer incidence in smokers and asbestos. This adverse effect may be explained by beta-Carotene prooxidant when tobacco smoke exposure and oxidative stress occurs, and cellular DNA damage was further aggrevated. Phase I enzymes were induced. Cell transformation was enhanced.

Socioeconomic development and urbanization have resulted in dramatic changes in cancer incidence and mortality in China. As one of the largest and most developed cities in China, Shanghai's cancer rates reflect the changing burden of cancer in China. This study was undertaken to evaluate trends and quantify changes in the incidence and mortality of breast, ovarian, endometrial, and cervical cancers among female residents of urban Shanghai from 1973 to 2009. Data on cancer incidence and mortality were collected by the Shanghai Cancer Registry. International Classification of Disease version 10 codes for breast (C50), cervical (C53), endometrial (corpus uteri and uterus unspecified; C54 and C55), and ovarian cancer (C56) were included in the current analysis. Annual population data was provided by the Department of Vital Statistics, Shanghai Municipal Center for Disease Control and Prevention. A total of 73,755 female cancers and 28,274 related deaths were documented between 1973 and 2009. Age-standardized incidence and mortality rates were calculated using the Segi/Doll 1960 world standard. Joinpoint regression models were used to fit joined straight lines on a log-scale for annual age-standardized rates and to calculate annual percent changes (APC). Between 1973 and 2009, the incidence of breast, ovarian, and endometrial cancers increased, with overall APCs of 2.93, 2.20, and 1.66, respectively. Significant trends were found for breast cancer between 1979 and 1998 (APC 3.07) and for ovarian cancer between 1983 and 2009 (APC 2.83). For endometrial cancer a significant decrease occurred from 1973 to 1983 (APC -4.27), followed by a significant increase from 1983 to 1996 (APC 2.58). The incidence of cervical cancer decreased, with an overall APC of -3.91; this included three significant decreasing trends between 1973 and 1996, followed by a significant increase through 2009 (APC 8.49). The mortality of breast and ovarian cancers increased, with overall APCs of 0.70 and 0.58, respectively. Significant trends were found for breast cancer between 1982 and 2004 (APC 1.55) and for ovarian cancer during the entire time period. The mortality of cervical and endometrial cancers decreased, with overall APCs of -5.36 and -2.33, respectively. For cervical cancer, this included a significant decrease between 1973 and 1999 (APC -7.34), followed by a significant increase through 2009 (APC 3.24). For endometrial cancer, this included a significant decrease between 1973 and 1988 (APC -5.59). In summary, increasing trends were found for breast, ovarian and endometrial cancer incidence, and for breast and ovarian cancer mortality, while decreasing trends were found for cervical cancer incidence and cervical and endometrial cancer mortality among women in urban Shanghai. Additional analyses to identify age-period-cohort effects in this data are underway. This study lays the ground work for the establishment of cancer prevention and control priorities in China. Citation Format: Zhezhou Huang, Alicia C. Beeghly-Fadiel, Ying Zheng, Wanqing Wen, Yutang Gao, Chunxiao Wu, Pingping Bao, Weijian Zhong, Fan Jin, Yongbing Xiang, Wei Zheng, Xiao Ou Shu, Wei Lu. Secular trends in incidence and mortality of female cancers in Shanghai, China (1973-2009). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4140. doi:10.1158/1538-7445.AM2014-4140

Background: Bone marrow aspirate concentrate (BMAC) including high densities of stem cells and progenitor cells may possess a stronger bone regenerative capability compared with Platelet-rich plasma (PRP), which contains enriched growth factors. The objective of this study was to evaluate the effects of human BMAC and PRP in combination with β-tricalcium phosphate (β-TCP) on promoting initial bone augmentation in an immunodeficient mouse model. Methodology/Principal Findings: BMAC and PRP were concentrated with an automated blood separator from the bone marrow and peripheral blood aspirates. β-TCP particles were employed as a scaffold to carry cells. After cell counting and FACS characterization, three groups of nude mice (BMAC+TCP, PRP+TCP, and a TCP control) were implanted with graft materials for onlay placement on the cranium. Samples were harvested after 4 weeks, and serial sections were prepared. We observed the new bone on light microscopy and performed histomorphometric analysis. After centrifugation, the concentrations of nucleated cells and platelets in BMAC were increased by factors of 2.8±0.8 and 5.3±2.4, respectively, whereas leucocytes and platelets in PRP were increased by factors of 4.1±1.8 and 4.4±1.9, respectively. The concentrations of CD34-, CD271-, CD90-, CD105-, and CD146-positive cells were markedly increased in both BMAC and PRP. The percentage of new bone in the BMAC group (7.6±3.9%) and the PRP group (7.2±3.8%) were significantly higher than that of TCP group (2.7±1.4%). Significantly more bone cells in the new bone occurred in sites transplanted with BMAC (552±257) and PRP (491±211) compared to TCP alone (187±94). But the difference between the treatment groups was not significant. Conclusions/Significance: Both human BMACs and PRP may provide therapeutic benefits in bone tissue engineering applications. These fractions possess a similar ability to enhance early-phase bone regeneration., PLoS ONE, 7(7), e40833; 2012

Abstract #1011 Background: Although sentinel lymph node biopsy (SLNB) has become the method of choice for axillary staging, the extent of the pathological examination (HE or IHC, the number or intervals of sections) described in the literature differed considerably between studies, particularly for the detection of micrometastases (MMs). As one of the second objectives of the CBCSG–001 trial (China multicenter study of sentinel node biopsy substituting axillary node dissection), our aim was to evaluate the optimal methods and intervals for the detection of SLN macrometastases, MMs and isolated tumor cells (ITCs). Material and Methods: Two hundred and forty-five continuous breast cancer patients with 569 SLNs identified “negative” with standard HE stain carried on initial 4 levels were retrospectively analyzed. All SLNs were step sectioned (SS) at 100µm interval, and for each level both HE and IHC with AE1/AE3 were performed. Then HE and IHC detection rates were analyzed at 100-, 200-, 300-, 400-, and 500µm intervals for the detection of macrometastases, MMs and ITCs. Results: In 245 cases with original SLN negative cases, 36 (14.7%), 49 (20.0%) and 49 (20.0%) cases were found to had metastases with SS HE, SS IHC, and SS HE+IHC, respectively (SS IHC/ SS HE+IHC vs. SS HE, p>0.05). In all the 5741 sections, metastases were found in 180 sections (3.1%) by SS HE, 307 (5.4%) by SS IHC, and 322 (5.6%) by SS HE+IHC (p=0.000). The metastases included macrometastases 12.2%, MMs 61.2%, and ITC 26.5%. The detection rates of MMs were 7.8%, 12.2%, and 12.2%, respectively (SS IHC/ SSHE+IHC vs. SS HE, p>0.05). The detection rates of ITCs were 4.5%, 5.3%, and 5.3%, respectively (p>0.05). The detection rates of metastases were significantly higher in patients with invasive lobular carcinoma (57.1%) than with invasive ductal carcinoma (16.7%, p=0.001), but no significant differences were found among different ages, tumor sizes, locations, grades, ER, PR, and HER-2 status (all p>0.05). The detection rates of metastases at 100-, 200-, 300-, 400-, and 500-µm intervals by SS HE were 14.7%, 13.5%, 11.4%, 8.6%, and 7.8%, respectively. No significant differences were found between 100- and 200-µm intervals (p=0.697), and between 100- and 300-µm (p=0.284), while p Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1011.

Abstract #1015 Background: China multicenter study of sentinel lymph node biopsy (SLNB) substituting axillary lymph node dissection (ALND) in breast cancer– CBCSG-001 trial was conducted from Jan. 2002 to Jun. 2007, with 1,970 SLNB pts recruitment. One of the second objectives of the CBCSG–001 trial was to evaluate the optimal methods and intervals for the detection of SLN macrometastases, MMs and isolated tumor cells (ITCs) and their prognostic significance in patients received SLNB without ALND or axillary radiotherapy. Material and Methods: Two hundred and forty-five continuous breast cancer patients with 569 SLNs identified “negative” with routine standard HE stain carried on initial 4 levels were retrospectively analyzed. All the patients received SLNB only, without ALND or axillary radiotherapy after the diagnoses of metastases in their SLNs later. All SLNs were step sectioned (SS) at 100µm interval, and for each level both HE and IHC with AE1/AE3 were performed. Forty-nine patients were identified to have metastases, with macrometastases of 12.2%, micrometastases of 61.2%, and isolated tumor cells of 26.5%. All patients had received SLNB only, with no ALND and axillary radiotherapy. Results: Of the 245 patients, breast conserved surgery and SLNB were performed on 106 patients (43.3%), and mastectomy and SLNB in 139 patients. With a median follow up of 50 months, there were 20 breast related events occurred. The disease free survival (DFS) of patients with routine negative SLNs was 91.6%, and 93.9% for patients with positive SLNs after SS with HE+IHC (p>0.05). The overall survival (OS) were 97.4% and 98.0 for each group, respectively (p>0.05). The results were the same for patients with macrometastases, micrometastases, and isolated tumor cells. Due to the relatively less events occurred, the DFS and OS had not been calculated for macrometastases, micrometastases, and isolated tumor cells, separately. Discussion and Conclusions: Without ALND and axillary radiotherapy, there were no significant differences of DFS and OS between patients with routine negative SLNs and patients with positive SLNs after SS with HE+IHC. It might be safe for these patients to receive SLNB only. The possible reasons might include: SLNs were the only positive lymph nodes in more than 60% patients, effective adjuvant systemic therapy for regional lymph nodes just as neoadjuvant chemotherapy, axillary coverage of radiotherapy in patients with breast conserved therapy, and the relatively less events occurred during the 50 months follow up period. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1015.