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Si-Man Cai,1 Hong-Yan Wang,1 Xiao-Yan Zhang,1 Li Zhang,1 Qing-Li Zhu,1 Jian-Chu Li,1 Qiang Sun,2 Yu-Xin Jiang1 1Department of Medical Ultrasound, Peking Union Medical College Hospital and Chinese Academy Medical Sciences, Beijing 100730, People’s Republic of China; 2Department of Breast Surgery, Peking Union Medical College Hospital and Chinese Academy Medical Sciences, Beijing 100730, People’s Republic of ChinaCorrespondence: Hong-Yan WangDepartment of Diagnostic Ultrasound, Peking Union Medical College Hospital, Chinese Academy Medical Sciences, N0.1 Shuai Fu Yuan, Dong Cheng District, Beijing 100730, People’s Republic of ChinaTel/Fax +86 10-69155494Email whychina@126.comPurpose: To investigate whether the vascular index (VI) of superb microvascular imaging (SMI) could improve the diagnostic efficiency for BI-RADS 4 breast lesions and reduce the number of unnecessary biopsies.Patients and Methods: For this study, we selected 222 consecutive BI-RADS 4 breast lesions detected by ultrasound and confirmed by pathology from January 2016 to October 2018. A VI of 4.0 was set as the cutoff value to degrade BI-RADS classification. We calculated the accuracy, sensitivity and PPV of a BI-RADS diagnosis alone and the combination of BI-RADS and the VI.Results: Pathologically, of the 222 lesions, 129 were confirmed to be benign, and 93 were found to be malignant. A VI of 4.0 was set as the cutoff value; when the VI≤ 4.0, those BI-RADS 4 masses were downgraded one level (4C-4B, 4B-4A, 4A-3) to an integral BI-RADS grade, while the others maintained the conventional grade. A total of 54 BI-RADS 4 lesions were degraded to BI-RADS 3, including 53 benign lesions and 1 malignant lesion. The diagnostic accuracy (65.3% vs 41.9%) and PPV (54.8% vs 41.9%) were significantly improved. The sensitivity decreased slightly (98.9% vs 100%) because 1 of the 54 downgraded BI-RADS 4 lesions, which had a pathological type of invasive ductal carcinoma, was incorrectly downgraded.Conclusion: SMI is a noninvasive tool for visualizing the vascular structure with high-resolution microvascular images. As a quantitative index, the VI can be used to appropriately downgrade benign lesions classified as BI-RADS 4, which can improve the diagnostic accuracy and PPV and reduce unnecessary biopsies.Keywords: superb microvascular imaging, breast neoplasms, ultrasonography, diagnostic imaging

Background: Cardioneuroablation (CNA) has shown encouraging results in patients with vasovagal syncope (VVS). However, data on different subtypes was scarce., Methods: This observational study retrospectively enrolled 141 patients [mean age: 40 ± 18 years, 51 males (36.2%)] with the diagnosis of VVS. The characteristics among different types of VVS and the outcomes after CNA were analyzed., Results: After a mean follow-up of 4.3 ± 1.5 years, 41 patients (29.1%) experienced syncope/pre-syncope events after CNA. Syncope/pre-syncope recurrence significantly differed in each subtype ( P = 0.04). The cardioinhibitory type of VVS had the lowest recurrence rate after the procedure ( n = 6, 16.7%), followed by mixed ( n = 26, 30.6%) and vasodepressive ( n = 9, 45.0%). Additionally, a significant difference was observed in the analyses of the Kaplan-Meier survival curve ( P = 0.02). Syncope/pre-syncope burden was significantly reduced after CNA in the vasodepressive type ( P < 0.01). Vasodepressive types with recurrent syncope/pre-syncope after CNA have a lower baseline deceleration capacity (DC) level than those without (7.4 ± 1.0 ms vs. 9.0 ± 1.6 ms, P = 0.01). Patients with DC < 8.4 ms had an 8.1 (HR = 8.1, 95% CI: 2.2-30.0, P = 0.02) times risk of syncope/pre-syncope recurrence after CNA compared to patients with DC ≥ 8.4 ms, and this association still existed after adjusting for age and sex (HR = 8.1, 95% CI: 2.2-30.1, P = 0.02)., Conclusions: Different subtypes exhibit different event-free rates. The vasodepressive type exhibited the lowest event-free rate, but those patients with DC ≥ 8.4 ms might benefit from CNA., (© 2024 JGC All rights reserved; www.jgc301.com.)

Describing travel patterns and identifying significant locations is a crucial area of research in transportation geography and social dynamics. Our study aims to contribute to this field by analyzing taxi trip data from Chengdu and New York City. Specifically, we investigate the probability density distribution of trip distance in each city, which enables us to construct long- and short-distance trip networks. To identify critical nodes within these networks, we employ the PageRank algorithm and categorize them using centrality and participation indices. Furthermore, we explore the factors that contribute to their influence and observe a clear hierarchical multi-centre structure in Chengdu's trip networks, while no such phenomenon is evident in New York City's. Our study provides insight into the impact of trip distance on important nodes within trip networks in both cities and serves as a reference for distinguishing between long and short taxi trips. Our findings also reveal substantial differences in network structures between the two cities, highlighting the nuanced relationship between network structure and socio-economic factors. Ultimately, our research sheds light on the underlying mechanisms shaping transportation networks in urban areas and offers valuable insights into urban planning and policy making.

With the development of information technology, more and more travel data have provided great convenience for scholars to study the travel behavior of users. Planning user travel has increasingly attracted researchers' attention due to its great theoretical significance and practical value. In this study, we not only consider the minimum fleet size required to meet the urban travel needs but also consider the travel time and distance of the fleet. Based on the above reasons, we propose a travel scheduling solution that comprehensively considers time and space costs, namely, the Spatial-Temporal Hopcroft-Karp (STHK) algorithm. The analysis results show that the STHK algorithm not only significantly reduces the off-load time and off-load distance of the fleet travel by as much as 81% and 58% and retains the heterogeneous characteristics of human travel behavior. Our study indicates that the new planning algorithm provides the size of the fleet to meet the needs of urban travel and reduces the extra travel time and distance, thereby reducing energy consumption and reducing carbon dioxide emissions. Concurrently, the travel planning results also conform to the basic characteristics of human travel and have important theoretical significance and practical application value., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Objective: To explore the effect of abnormal miRNA expression on the proliferation of pediatric acute lymphoblastic leukemia (ALL) cells and its related mechanism., Methods: 15 children with ALL and 15 healthy subjects were collected from the Second Affiliated Hospital of Hainan Medical University from July 2018 to March 2021. MiRNA sequencing was performed on their bone marrow cells, and validated using qRT-PCR. MiR-1294 and miR-1294-inhibitory molecule (miR-1294-inhibitor) were transfected into Nalm-6 cells, and the proliferation of Nalm-6 cells was detected by CCK-8 and colony formation assays. Western blot and ELISA were used to detect apoptosis of Nalm-6 cells. Biological prediction of miR-1294 was performed to find the target gene, which was verified by luciferase reporter assay. Si- SOX15 was transfected into Nalm-6 cells, Western blot was used to detect the expression of Wnt signaling pathway-related proteins and to verify the effect of si- SOX15 on the proliferation and apoptosis of Nalm-6 cells., Results: Compared with healthy subjects, 22 miRNAs were significantly upregulated in bone marrow cells of ALL patients, of which miR-1294 was the most significantly upregulated. In addition, the expression level of SOX15 gene was significantly reduced in bone marrow cells of ALL patients. Compared with the NC group, the miR-1294 group showed increased protein expression levels of Wnt3a and β-catenin, faster cell proliferation, and more colony-forming units, while caspase-3 protein expression level and cell apoptosis were reduced. Compared with the NC group, the miR-1294-inhibitor group showed reduced protein expression levels of Wnt3a and β-catenin, slower cell proliferation, and fewer colony-forming units, while caspase-3 protein expression level was increased and apoptosis rate was elevated. miR-1294 had a complementary base-pair with the 3'UTR region of SOX15 , and miR-1294 directly targeted SOX15 . The expression of miR-1294 was negatively correlated with SOX15 in ALL cells. Compared with the si-NC group, the si- SOX15 group showed increased protein expression levels of Wnt3a and β-catenin, accelerated cell proliferation, and decreased caspase-3 protein expression level and cell apoptosis rate., Conclusion: MiR-1294 can target and inhibit SOX15 expression, thus activating the Wnt/β-Catenin signaling pathway to promote the proliferation of ALL cells, inhibit cell apoptosis, and ultimately affect the disease progression.

Background: To determine whether vascular index (VI; defined as the ratio of Doppler signal pixels to pixels in the total lesion) measured via superb microvascular imaging in breast cancer correlates with immunohistochemically defined subtype and is able to predict molecular subtypes., Methods: This prospective study involved 225 patients with 225 mass-type invasive breast cancers (mean size 2.6 ± 1.4 cm, range 0.4~5.9 cm) who underwent ultrasound and superb microvascular imaging (SMI) at Peking Union Medical College Hospital before breast surgery from December 2016 to June 2018. The correlations between primary tumor VI measured via SMI, clinicopathological findings, and molecular subtype were analyzed. The performance of VI for prediction of molecular subtypes in invasive breast cancer was investigated., Results: The median VI of the 225 tumors was 7.3% (4.2%~11.8%) (range 0%~54.4%). Among the subtypes of the 225 tumors, 41 (18.2%) were luminal A, 91 (40.4%) were luminal B human epidermal growth factor receptor-2 (HER-2)-negative, 26 (11.6%) were luminal B HER-2-positive, 17 (7.6%) were HER-2-positive, and 50 (22.2%) were triple-negative, and the corresponding median VI values were 5.9% (2.6%~11.6%) (range 0%~47.1%), 7.3 (4.4%~10.5%) (range 0%~29.5%), 6.3% (3.9%~11.3%) (range 0.6%~22.2%), 8.2% (4.9%~15.6%) (range 0.9%~54.4%), and 9.2% (5.1%~15.3%) (range 0.7%~32.9%), respectively. Estrogen receptor (ER) negativity, higher tumor grade, and higher Ki-67 index (≥20%) were significantly associated with a higher VI value. Tumor size, ER status, and Ki-67 index were shown to independently influence VI. A cutoff value of 4.1% yielded 79.9% sensitivity and 41.5% specificity with an area under the receiver operating characteristic curve (AUC) of 0.58 for predicting that a tumor was of the luminal A subtype. A cutoff value of 16.4% yielded 30.0% sensitivity and 90.3% specificity with an AUC of 0.60 for predicting a triple-negative subtype., Conclusions: VI, as a quantitative index obtained by SMI examination, could reflect histologic vascular changes in invasive breast cancer and was found to be higher in more biologically aggressive breast tumors. VI shows a certain degree of correlation with the molecular subtype of invasive breast cancer and plays a limited role in predicting the luminal A with high sensitivity and triple-negative subtype with high specificity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2022 Zhang, Cai, Zhang, Zhu, Sun, Jiang, Wang and Li.)

Background: Early-stage breast cancer patients often lack specific clinical manifestations, making diagnosis difficult. Molybdenum target X-ray and magnetic resonance imaging (MRI) examinations both have their own advantages. Thus, a combined examination methodology may improve early breast cancer diagnoses., Aim: To explore the combined diagnostic efficacy of molybdenum target X-ray and MRI examinations in breast cancer., Methods: Patients diagnosed with breast cancer at our hospital from March 2019 to April 2021 were recruited, as were the same number of patients during the same period with benign breast tumors. Both groups underwent molybdenum target X-ray and MRI examinations, and diagnoses were given based on each exam. The single ( i.e., X-ray or MRI) and combined ( i.e., using both methods) diagnoses were counted, and the MRI-related examination parameters ( e.g., T-wave peak, peak and early enhancement rates, and apparent diffusion coefficient) were compared between the groups., Results: In total, 63 breast cancer patients and 63 benign breast tumor patients were recruited. MRI detected 53 breast cancer cases and 61 benign breast tumor cases. Molybdenum target X-ray detected 50 breast cancer cases and 60 benign breast tumor cases. The combined methodology detected 61 breast cancer cases and 61 benign breast tumor cases. The sensitivity (96.83%) and accuracy (96.83%) of the combined methodology were higher than single-method MRI (84.13% and 90.48%, respectively) and molybdenum target X-ray (79.37% and 87.30%, respectively) ( P < 0.05). The combined methodology specificity (96.83%) did not differ from single-method MRI (96.83%) or molybdenum target X-ray (95.24%) ( P > 0.05). The T-wave peak (169.43 ± 32.05) and apparent diffusion coefficient (1.01 ± 0.23) were lower in the breast cancer group than in the benign tumor group (228.86 ± 46.51 and 1.41 ± 0.35, respectively). However, the peak enhancement rate (1.08 ± 0.24) and early enhancement rate (1.07 ± 0.26) were significantly higher in the breast cancer group than in the benign tumor group (0.83 ± 0.19 and 0.75 ± 0.19, respectively) ( P < 0.05)., Conclusion: Combined molybdenum target X-ray and MRI examinations for diagnosing breast cancer improved the diagnostic sensitivity and accuracy, minimizing the missed- and misdiagnoses risks and promoting timely treatment intervention., Competing Interests: Conflict-of-interest statement: No conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

As there is no clear biomarker to diagnose Parkinson's disease, this meta-analysis aims to comprehensively evaluates the correlation between serum Cystatin C levels and Parkinson's disease in the Chinese population by the meta-analysis method. PubMed, Web of Science, Embase, Cochrane Library, China national knowledge infrastructure, and China WanFang databases were systematically searched on the correlation between serum Cystatin C and Parkinson's disease. The results showed that Cystatin C level in Parkinson's disease patients compared with the control group, the standardized mean difference = 1.78 (95% CI: 1.33~2.24, P < 0.05). The level of Cystatin C in the late Parkinson's disease stage compared with that in the mid-term of Parkinson's disease, the standardized mean difference was = 0.78 (95% CI: 0.08~1.49, P < 0.05). The Cystatin C level in the mid-term of Parkinson's disease compared with that in the early Parkinson's disease stage, the standardized mean difference was 1.24 (95% CI: 0.35~2.12, P < 0.05). The level of Cystatin C in Parkinson's disease with mild cognitive impairment compared with Parkinson's disease without mild cognitive impairment, the standardized mean difference was 1.29 (95% CI: 0.47~2.10, P < 0.05). The differences were all statistically significant. In conclusion, a high level of serum Cystatin C may be involved in the occurrence and development of Parkinson's disease, whose level is higher in Parkinson's disease patients with mild cognitive impairment than that in Parkinson's disease without mild cognitive impairment. Therefore, Cystatin C in serum is a promising biomarker for diagnosing Parkinson's disease., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by IMR Press.)

Background: Technological and research advances have produced large volumes of biomedical data. When represented as a network (graph), these data become useful for modeling entities and interactions in biological and similar complex systems. In the field of network biology and network medicine, there is a particular interest in predicting results from drug-drug, drug-disease, and protein-protein interactions to advance the speed of drug discovery. Existing data and modern computational methods allow to identify potentially beneficial and harmful interactions, and therefore, narrow drug trials ahead of actual clinical trials. Such automated data-driven investigation relies on machine learning techniques. However, traditional machine learning approaches require extensive preprocessing of the data that makes them impractical for large datasets. This study presents wide range of machine learning methods for predicting outcomes from biomedical interactions and evaluates the performance of the traditional methods with more recent network-based approaches., Results: We applied a wide range of 32 different network-based machine learning models to five commonly available biomedical datasets, and evaluated their performance based on three important evaluations metrics namely AUROC, AUPR, and F1-score. We achieved this by converting link prediction problem as binary classification problem. In order to achieve this we have considered the existing links as positive example and randomly sampled negative examples from non-existant set. After experimental evaluation we found that Prone, ACT and [Formula: see text] are the top 3 best performers on all five datasets., Conclusions: This work presents a comparative evaluation of network-based machine learning algorithms for predicting network links, with applications in the prediction of drug-target and drug-drug interactions, and applied well known network-based machine learning methods. Our work is helpful in guiding researchers in the appropriate selection of machine learning methods for pharmaceutical tasks.

City taxi service systems have been empirically studied by a number of data-driven methods. However, their underlying mechanisms are hard to understand because the present mathematical models neglect to explain a (whole) taxi service process that includes a pair of on-load phase and off-load phase. In this paper, by analyzing a large amount of taxi servicing data from a large city in China, we observe that the taxi service process shows different temporal and spatial features according to the on-load phase and off-load phase. Moreover, our correlation analysis results demonstrate the lack of dependence between the on-load phase and the off-load phase. Hence, we introduce two independent random walk models based on the Langevin equation to describe the underlying mechanism and to understand the temporal and spatial features of the taxi service process. Our study attempts to formulate the mathematical framework for simulating the taxi service process and better understanding of its underlying mechanism.

Epidemic spreading processes in the real world depend on human behaviors and, consequently, are typically non-Markovian in that the key events underlying the spreading dynamics cannot be described as a Poisson random process and the corresponding event time is not exponentially distributed. In contrast to Markovian type of spreading dynamics for which mathematical theories have been well developed, we lack a comprehensive framework to analyze and fully understand non-Markovian spreading processes. Here we develop a mean-field theory to address this challenge, and demonstrate that the theory enables accurate prediction of both the transient phase and the steady states of non-Markovian susceptible-infected-susceptible spreading dynamics on synthetic and empirical networks. We further find that the existence of equivalence between non-Markovian and Markovian spreading depends on a specific edge activation mechanism. In particular, when temporal correlations are absent on active edges, the equivalence can be expected; otherwise, an exact equivalence no longer holds.

Synchronization in complex networks characterizes what happens when an ensemble of oscillators in a complex autonomous system become phase-locked. We study the Kuramoto model with a tunable phase-lag parameter α in the coupling term to determine how phase shifts influence the synchronization transition. The simulation results show that the phase frustration parameter leads to desynchronization. We find two global synchronization regions for α∈[0,2π) when the coupling is sufficiently large and detect a relatively rare network synchronization pattern in the frustration parameter near α=π. We call this frequency-locking configuration as "repulsive synchronization," because it is induced by repulsive coupling. Since the repulsive synchronization cannot be described by the usual order parameter r, the parameter frequency dispersion is introduced to detect synchronization.

Resources are limited in epidemic containment; how to optimally allocate the limited resources in suppressing the epidemic spreading has been a challenging problem. To find an effective resource allocation strategy, we take the infectiousness of each infected node into consideration. By studying the interplay between the resource allocation and epidemic spreading, we find that the spreading dynamics of epidemic is affected by the preferential resource allocation. There are double phase transitions of the fraction of infected nodes, which are different from the classical epidemic model. More importantly, we find that the preferential resource allocation has double-edged sword effects on the disease spreading. When there is a small transmission rate, the infected fraction at the steady state decreases with the increment of degree of resource allocation preference, which indicates that resources of the healthy nodes should be allocated preferentially to the high infectious nodes to constrain the disease spreading. Moreover, when there is a large transmission rate, the fraction of infected nodes at the steady state increases with the increment of the degree of the preference, but the resource allocation is determined by the stage of epidemic spreading. Namely, in the early stage of the disease spreading, resources should be allocated preferentially to the high infectious nodes similar to the case of a small transmission rate. While after the early stage, resources should be allocated to the low infectious nodes. Based on the findings, we propose a simple resource allocation strategy that can adaptively change with the current fraction of infected nodes and the disease can be suppressed to the most extent under the proposed strategy.

One of the most challenging problems in network science is to accurately detect communities at distinct hierarchical scales. Most existing methods are based on structural analysis and manipulation, which are NP-hard. We articulate an alternative, dynamical evolution-based approach to the problem. The basic principle is to computationally implement a nonlinear dynamical process on all nodes in the network with a general coupling scheme, creating a networked dynamical system. Under a proper system setting and with an adjustable control parameter, the community structure of the network would "come out" or emerge naturally from the dynamical evolution of the system. As the control parameter is systematically varied, the community hierarchies at different scales can be revealed. As a concrete example of this general principle, we exploit clustered synchronization as a dynamical mechanism through which the hierarchical community structure can be uncovered. In particular, for quite arbitrary choices of the nonlinear nodal dynamics and coupling scheme, decreasing the coupling parameter from the global synchronization regime, in which the dynamical states of all nodes are perfectly synchronized, can lead to a weaker type of synchronization organized as clusters. We demonstrate the existence of optimal choices of the coupling parameter for which the synchronization clusters encode accurate information about the hierarchical community structure of the network. We test and validate our method using a standard class of benchmark modular networks with two distinct hierarchies of communities and a number of empirical networks arising from the real world. Our method is computationally extremely efficient, eliminating completely the NP-hard difficulty associated with previous methods. The basic principle of exploiting dynamical evolution to uncover hidden community organizations at different scales represents a "game-change" type of approach to addressing the problem of community detection in complex networks.

Objective: We report a case of intractable circulatory failure event in a hypertensive patient during laparoscopy hepatectomy and analyze the diagnosis and treatment by multidisciplinary physicians. This case suggests that both surgeons and anesthesiologists should give attention to oral angiotensin II receptor antagonist during the preoperative period to avoid refractory hypotension. In addition, the use of EV1000 hemodynamic monitoring system in intensive care provides more convenience for clinical liquid management.

Synergistic interactions are ubiquitous in the real world. Recent studies have revealed that, for a single-layer network, synergy can enhance spreading and even induce an explosive contagion. There is at the present a growing interest in behavior spreading dynamics on multiplex networks. What is the role of synergistic interactions in behavior spreading in such networked systems? To address this question, we articulate a synergistic behavior spreading model on a double layer network, where the key manifestation of the synergistic interactions is that the adoption of one behavior by a node in one layer enhances its probability of adopting the behavior in the other layer. A general result is that synergistic interactions can greatly enhance the spreading of the behaviors in both layers. A remarkable phenomenon is that the interactions can alter the nature of the phase transition associated with behavior adoption or spreading dynamics. In particular, depending on the transmission rate of one behavior in a network layer, synergistic interactions can lead to a discontinuous (first-order) or a continuous (second-order) transition in the adoption scope of the other behavior with respect to its transmission rate. A surprising two-stage spreading process can arise: due to synergy, nodes having adopted one behavior in one layer adopt the other behavior in the other layer and then prompt the remaining nodes in this layer to quickly adopt the behavior. Analytically, we develop an edge-based compartmental theory and perform a bifurcation analysis to fully understand, in the weak synergistic interaction regime where the dynamical correlation between the network layers is negligible, the role of the interactions in promoting the social behavioral spreading dynamics in the whole system.

Although recent studies have found that the long-term correlations relating to the fat-tailed distribution of inter-event times exist in human activity and that these correlations indicate the presence of fractality, the property of fractality and its origin have not been analyzed. We use both detrended fluctuation analysis and multifractal detrended fluctuation analysis to analyze the time series in online viewing activity separating from Movielens and Netflix. We find long-term correlations at both the individual and communal levels and that the extent of correlation at the individual level is determined by the activity level. These long-term correlations also indicate that there is fractality in the pattern of online viewing. We first find a multifractality that results from the combined effect of the fat-tailed distribution of inter-event times (i.e., the times between successive viewing actions of individuals) and the long-term correlations in online viewing activity and verify this finding using three synthesized series. Therefore, it can be concluded that the multifractality in online viewing activity is caused by both the fat-tailed distribution of inter-event times and the long-term correlations and that this enlarges the generic property of human activity to include not just physical space but also cyberspace.

Methods used in information filtering and recommendation often rely on quantifying the similarity between objects or users. The used similarity metrics often suffer from similarity redundancies arising from correlations between objects' attributes. Based on an unweighted undirected object-user bipartite network, we propose a Corrected Redundancy-Eliminating similarity index (CRE) which is based on a spreading process on the network. Extensive experiments on three benchmark data sets-Movilens, Netflix and Amazon-show that when used in recommendation, the CRE yields significant improvements in terms of recommendation accuracy and diversity. A detailed analysis is presented to unveil the origins of the observed differences between the CRE and mainstream similarity indices.

The present study was designed to investigate the anti-sepsis effects of physcion 8-O-β-glucopyranoside (POG) isolated from Rumex japonicas and explore its possible pharmacological mechanisms. POG was extracted from R. japonicas by bioactivity-guided isolation with the anti-sepsis agents. Survival analysis in septic mouse induced by LPS and heat-killed Escherichia coli were used to evaluate the protective effect of POG (40 mg·kg -1 , i.p.) on sepsis. Cytokines including TNF-α, IL-1β and IL-6 in RAW 264.7 cells induced by LPS (100 ng·mL -1 ) were determined by ELISA. In addition, the proteins expressions of TLR2 and TLR4 were determined by Western blotting assay. Our results demonstrated that POG (40 mg·kg -1 , i.p.) possessed significant protective activity on the endotoxemic mice. The POG treatment (20, 40, and 80 μg·mL -1 ) significantly decreased the TNF-α, IL-1β and IL-6 induced by LPS (P < 0.01) in a concentration-dependent manner. Furthermore, the TLR4 and TLR2 proteins were also down-regulated by POG at 20 (P < 0.01), 40 (P < 0.01), and 80 μg·mL -1 (P < 0.01). The present study demonstrated that the POG extracted from R. japonicas possessed significant anti-sepsis effect on endotoxemic mice, and can be developed as a novel drug for treating sepsis in the future., (Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Time-varying community structures exist widely in real-world networks. However, previous studies on the dynamics of spreading seldom took this characteristic into account, especially those on social contagions. To study the effects of time-varying community structures on social contagions, we propose a non-Markovian social contagion model on time-varying community networks based on the activity-driven network model. A mean-field theory is developed to analyze the proposed model. Through theoretical analyses and numerical simulations, two hierarchical features of the behavior adoption processes are found. That is, when community strength is relatively large, the behavior can easily spread in one of the communities, while in the other community the spreading only occurs at higher behavioral information transmission rates. Meanwhile, in spatial-temporal evolution processes, hierarchical orders are observed for the behavior adoption. Moreover, under different information transmission rates, three distinctive patterns are demonstrated in the change of the whole network's final adoption proportion along with the growing community strength. Within a suitable range of transmission rate, an optimal community strength can be found that can maximize the final adoption proportion. Finally, compared with the average activity potential, the promoting or inhibiting of social contagions is much more influenced by the number of edges generated by active nodes.

Diverse fungal endophytes are rich fungal resources for the production of an enormous quantity of natural products. In the present study, 53 fungal endophytes were isolated from the bulbs of Fritillaria unibracteata var. wabuensis (FUW). Of these, 49 strains were identified and grouped into 17 different taxa, and priority was conferred to the Fusarium genus. All fungal fermented filtrates displayed antioxidant activities. The DPPH activity, total antioxidant capacities (ABTS), reduction power (FRAP), total phenolic content (TPC), total flavonoid content (TFC) and total saponin content (TSC) were evaluated using petroleum ether, ethyl acetate, n-butyl alcohol and ethanol fractions extracted from five representative fungal cultures. The last three fractions showed more potent antioxidant activity than the first fraction. Significant positive correlations were found between the compositions (TPC, TFC and TSC) and antioxidant capacities (DPPH, ABTS and FRAP). In addition, multifarious natural antioxidant components were identified from the fungal extracts, including gallic acid, rutin, phlorizin, 2,4-di-tert-butylphenol and 2,6-di-tert-butyl hydroquinone; these were determined preliminarily by TLC-bioautography, HPLC and GC-MS analysis. This study showed abundant fungal resources in FUW. Phenolics, flavonoids and saponins are crucial bioactive constituents in these abundant fungal endophytes and can be viewed as new potential antioxidant resources., Competing Interests: The authors declare no competing financial interests.

Although there is always an interplay between the dynamics of information diffusion and disease spreading, the empirical research on the systemic coevolution mechanisms connecting these two spreading dynamics is still lacking. Here we investigate the coevolution mechanisms and dynamics between information and disease spreading by utilizing real data and a proposed spreading model on multiplex network. Our empirical analysis finds asymmetrical interactions between the information and disease spreading dynamics. Our results obtained from both the theoretical framework and extensive stochastic numerical simulations suggest that an information outbreak can be triggered in a communication network by its own spreading dynamics or by a disease outbreak on a contact network, but that the disease threshold is not affected by information spreading. Our key finding is that there is an optimal information transmission rate that markedly suppresses the disease spreading. We find that the time evolution of the dynamics in the proposed model qualitatively agrees with the real-world spreading processes at the optimal information transmission rate.

Aims: Angiotensin II (Ang II) aggravates hepatic fibrosis by inducing NADPH oxidase (NOX)-dependent oxidative stress. Angiotensin-(1-7) [Ang-(1-7)], which counter-regulates Ang II, has been evidenced to protect against hepatic fibrosis. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, being activated by reactive oxygen species (ROS), is identified as a novel mechanism of liver fibrosis. However, whether the NLRP3 inflammasome involves in regulation of Ang II-induced hepatic fibrosis remains unclear. This study investigates the different effects of the Ang II and Ang-(1-7) on collagen synthesis by regulating the NLRP3 inflammasome/Smad pathway via redox balance modulation., Results: In vivo, Ang-(1-7) improved bile duct ligation-induced hepatic fibrosis, reduced H2O2 content, protein levels of NOX4, and the NLRP3 inflammasome, whereas it increased glutathione (GSH) and nuclear erythroid 2-related factor 2 (Nrf2) antioxidant response element (ARE). In vitro, Ang II treatment elevated NOX4 protein expression and ROS production in hepatic stellate cells (HSCs), whereas it inhibited GSH and Nrf2-ARE, resulting in the activation of the NLRP3 inflammasome in the mitochondria of HSCs. NLRP3 depletion inhibited Ang II-induced collagen synthesis. Furthermore, Ang II increased NLRP3 and pro-IL-1β levels by activating the Toll-like receptor 4 (TLR4)/MyD88/NF-κB pathway. Treatment with antioxidants, NOX4 small interference RNA (siRNA), or Nrf2 activator inhibited Ang II-induced NLRP3 inflammasome activation and collagen synthesis. In contrast, the action of Ang-(1-7) opposed the effects of Ang II., Innovation and Conclusions: Ang-(1-7) improved liver fibrosis by regulating NLRP3 inflammasome activation induced by Ang II-mediated ROS via redox balance modulation. Antioxid. Redox Signal. 24, 795-812.

Controlling complex networks is of paramount importance in science and engineering. Despite recent efforts to improve controllability and synchronous strength, little attention has been paid to the speed of pinning synchronizability (rate of convergence in pinning control) and the corresponding pinning node selection. To address this issue, we propose a hypothesis to restrict the control cost, then build a linear matrix inequality related to the speed of pinning controllability. By solving the inequality, we obtain both the speed of pinning controllability and optimal control strength (feedback gains in pinning control) for all nodes. Interestingly, some low-degree nodes are able to achieve large feedback gains, which suggests that they have high influence on controlling system. In addition, when choosing nodes with high feedback gains as pinning nodes, the controlling speed of real systems is remarkably enhanced compared to that of traditional large-degree and large-betweenness selections. Thus, the proposed approach provides a novel way to investigate the speed of pinning controllability and can evoke other effective heuristic pinning node selections for large-scale systems.

High stocking density (STD) could affect duck welfare and production. The objective of our study was to investigate whether dietary tryptophan (TRP) supplementation could alleviate the detrimental effects of high STD on ducks. White Pekin ducks at 4 to 6 wk of age were raised at 11 birds/m(2) and fed diets containing 0.18, 0.48, 0.78, or 1.08% TRP for 21 d. Growth performance, concentrations of TRP and metabolites in the blood and hypothalamus, antioxidative activities in serum and tissue, meat quality, serum uric acid, and urea nitrogen were measured. Weight gain and feed efficiency were significantly improved by TRP supplementation at ≥ 0.48 and ≥ 0.78% (P < 0.05 and P < 0.001, respectively). Serum TRP, hypothalamic TRP, 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacitic acid (5-HIAA), and 5-HIAA/5-HT were also increased significantly (P < 0.01). These increases plateaued at 0.48% TRP, and no further improvement was obtained by adding more TRP to the diet. Dietary TRP supplementation significantly increased levels of total antioxidant capacity, glutathione peroxidase (GSH-Px), and catalase (CAT) in serum; GSH-Px in liver; and GSH-Px and CAT in breast muscle (P < 0.05). Malondialdehyde levels in breast muscle decreased (P < 0.001). Drip loss of breast muscle and pH decline at 45 min postmortem were reduced by TRP supplementation (P < 0.01 and P < 0.05, respectively). Meat color was similar among different treatments (P > 0.05). Breast muscle shear force was increased significantly when dietary TRP level increased to 1.08% (P < 0.01). For ducks raised at 11 birds/m², dietary TRP supplementation could alleviate stress and improve growth performance, antioxidative activity, and meat quality., (© 2015 Poultry Science Association Inc.)

The dynamics of human mobility characterizes the trajectories that humans follow during their daily activities and is the foundation of processes from epidemic spreading to traffic prediction and information recommendation. In this paper, we investigate a massive data set of human activity, including both online behavior of browsing websites and offline one of visiting towers based mobile terminations. The non-Markovian character observed from both online and offline cases is suggested by the scaling law in the distribution of dwelling time at individual and collective levels, respectively. Furthermore, we argue that the lower entropy and higher predictability in human mobility for both online and offline cases may originate from this non-Markovian character. However, the distributions of individual entropy and predictability show the different degrees of non-Markovian character between online and offline cases. To account for non-Markovian character in human mobility, we apply a protype model with three basic ingredients, namely, preferential return, inertial effect, and exploration to reproduce the dynamic process of online and offline human mobilities. The simulations show that the model has an ability to obtain characters much closer to empirical observations.

Community structure can naturally emerge in paths to synchronization, and scratching it from the paths is a tough issue that accounts for the diverse dynamics of synchronization. In this paper, with assumption that the synchronization on complex networks is made up of local and collective processes, we proposed a scheme to lock the local synchronization (phase locking) at a stable state, meanwhile, suppress the collective synchronization based on Kuramoto model. Through this scheme, the network dynamics only contains the local synchronization, which suggests that the nodes in the same community synchronize together and these synchronization clusters well reveal the community structure of network. Furthermore, by analyzing the paths to synchronization, the relations or overlaps among different communities are also obtained. Thus, the community detection based on the scheme is performed on five real networks and the observed community structures are much more apparent than modularity-based fast algorithm. Our results not only provide a deep insight to understand the synchronization dynamics on complex network but also enlarge the research scope of community detection.

Objective: To explore the inhibitory effect of angiotensin (1-7) on hepatic sinusoid angiogenesis using a rat model of hepatic fibrosis., Methods: Eighteen male Wistar rats were randomly divided into three equal groups for sham operation (untreated/uninduced control group), bile duct ligation (BDL) (untreated model group), or BDL with angiotensin (1-7) treatment (treated model group). Histological analysis was used to assess the liver fibrosis score, by hematoxylin-eosin staining, and the level of fibrosis, by Masson's trichrome staining. Immunohistochemistry, western blotting, and immunofluorescence were used to assess the expression of the angiogenesis markers vWF, VEGFA, and CD31., Results: Compared with the untreated/uninduced control group, the untreated BDL model group showed remarkably higher fibrosis score, area of the type I collagen expression, and expression levels of vWF, VEGFA, and CD31. However, the angiotensin (1-7)-treatment protected against the BLD-related changes, as evidenced by decreased robustness and down-regulation of the corresponding indicators. Moreover, the expression level of VEGFA was highly correlated to the expression level of vWF (r = 0.956, P = 0.000)., Conclusion: BDL-induced hepatic fibrosis is accompanied by significant increases in angiogenesis-related factors, but angiotensin (1-7) treatment may inhibit hepatic sinusoid angiogenesis during the liver fibrosis process.

We sought to analyze the dynamic properties of brain electrical activity from healthy volunteers and epilepsy patients using recurrence networks. Phase-space trajectories of synchronous electroencephalogram signals were obtained through embedding dimension in phase-space reconstruction based on the distance set of space points. The recurrence matrix calculated from phase-space trajectories was identified with the adjacency matrix of a complex network. Then, we applied measures to characterize the complex network to this recurrence network. A detailed analysis revealed the following: (1) The recurrence networks of normal brains exhibited a sparser connectivity and smaller clustering coefficient compared with that of epileptic brains; (2) the small-world property existed in both normal and epileptic brains consistent with the previous empirical studies of structural and functional brain networks; and (3) the assortative property of the recurrence network was found by computing the assortative coefficients; their values increased from normal to epileptic brain which accurately suggested the difference of the states. These universal and non-universal characteristics of recurrence networks might help clearly understand the underlying neurodynamics of the brain and provide an efficient tool for clinical diagnosis.

In this paper, we investigate a synchronization-based, data-driven clustering approach for the analysis of functional magnetic resonance imaging (fMRI) data, and specifically for detecting functional activation from fMRI data. We first define a new measure of similarity between all pairs of data points (i.e., time series of voxels) integrating both complete phase synchronization and amplitude correlation. These pairwise similarities are taken as the coupling between a set of Kuramoto oscillators, which in turn evolve according to a nearest-neighbor rule. As the network evolves, similar data points naturally synchronize with each other, and distinct clusters will emerge. The clustering behavior of the interaction network of the coupled oscillators, therefore, mirrors the clustering property of the original multiple time series. The clustered regions whose cross-correlation coefficients are much greater than other regions are considered as the functionally activated brain regions. The analysis of fMRI data in auditory and visual areas shows that the recognized brain functional activations are in complete correspondence with those from the general linear model of statistical parametric mapping, but with a significantly lower time complexity. We further compare our results with those from traditional K-means approach, and find that our new clustering approach can distinguish between different response patterns more accurately and efficiently than the K-means approach, and therefore more suitable in detecting functional activation from event-related experimental fMRI data.

The functional network of the brain is known to demonstrate modular structure over different hierarchical scales. In this paper, we systematically investigated the hierarchical modular organizations of the brain functional networks that are derived from the extent of phase synchronization among high-resolution EEG time series during a visual task. In particular, we compare the modular structure of the functional network from EEG channels with that of the anatomical parcellation of the brain cortex. Our results show that the modular architectures of brain functional networks correspond well to those from the anatomical structures over different levels of hierarchy. Most importantly, we find that the consistency between the modular structures of the functional network and the anatomical network becomes more pronounced in terms of vision, sensory, vision-temporal, motor cortices during the visual task, which implies that the strong modularity in these areas forms the functional basis for the visual task. The structure-function relationship further reveals that the phase synchronization of EEG time series in the same anatomical group is much stronger than that of EEG time series from different anatomical groups during the task and that the hierarchical organization of functional brain network may be a consequence of functional segmentation of the brain cortex.

Background: Mucinous epithelial ovarian cancer (mEOC) may exhibit a distinct biological behavior in epithelial ovarian cancer (EOC). The role of secondary cytoreductive surgery was evaluated in patients with recurrent mEOC, and the prognosis was assessed., Methods: Twenty-one patients with stages IIc to IV mEOC who experienced disease recurrence and received secondary cytoreductive surgery at Fudan University Cancer Hospital between Jan. 1997 and Dec. 2005 were retrospectively reviewed. Survival curves were generated using the Kaplan-Meier method and the significant comparison of survival rate was estimated by the log-rank test., Results: The median progression-free interval (PFI) was 14 months (range, 5-46 months) after the first cytoreduction. Seven patients (33%) who received secondary cytoreductive surgery were optimally cytoreduced with residual disease less than or equal 1cm, and the other 14 patients (67%) underwent suboptimal surgical cytoreduction. The overall median survival time was 27 months (range, 8-64 months). The median survival time after recurrence was 10 months (range, 3-32 months). There was no significant statistical difference in median survival between patients with optimal and suboptimal secondary surgical cytoreduction, with an estimated survival of 10 months and 9.8 months, respectively (P>0.05)., Conclusion: Optimal primary cytoreductive surgery for advanced mEOC was very important. Once it recurs, the prognosis is very poor. Patients with recurrent mEOC should be carefully assessed before performing secondary cytoreductive surgery, as this may have limited impact on the overall survival rates.

The purpose of this retrospective study was to report our experience with concurrent chemotherapy and adjuvant extended field irradiation after radical surgery for cervical carcinoma patients with common iliac node and/or multiple pelvic lymph nodes metastases. We studied 25 patients with FIGO stage IB-IIB (IB, 3; IIA, 15; and IIB, 7) cervical carcinoma who underwent radical surgery and had histologically confirmed involvement of common iliac nodes and/or multiple (>or=2) pelvic lymph nodes. These patients received the first cycle of systemic chemotherapy 2 weeks after radical surgery. Then, they received pelvic and extended field irradiation (40-45 Gy) with weekly cisplatinum (30 mg/m(2)). They were then given five more cycles of consolidation chemotherapy. Survival curves were generated by the Kaplan-Meier method. The 3-year progression-free survival (PFS) and overall survival rates were 63% and 76%, respectively. The PFS rates with multiple pelvic node and common iliac node metastases were 69% and 61%, respectively. The pelvic recurrence rate was 8% (2/25) and that for distant metastases was 32% (8/25). No patient's treatment failed in the para-aortic region. The median interval from the surgery to the recurrence was 14 months (range, 5-29 months). Nineteen (76%) patients experienced grades 1-2 and four (16%) experienced grades 3-4 neutropenia. Fifteen patients (60%) experienced grades 1-2 and one (4%) experienced grades 3-4 gastrointestinal toxicity. Concurrent chemotherapy and adjuvant extended field irradiation after radical surgery achieved good local control with acceptable toxicity. However, subsequent distant metastasis was still the predominant form of treatment failure even after consolidation chemotherapy.

In this paper, we investigate the dynamical properties of electroencephalogram (EEG) signals of humans in sleep. By using a modified random walk method, we demonstrate that scale-invariance is embedded in EEG signals after a detrending procedure is applied. Furthermore, we study the dynamical evolution of the probability density function (PDF) of the detrended EEG signals by nonextensive statistical modeling. It displays a scale-independent property, which is markedly different from the usual scale-dependent PDF evolution and cannot be described by the Fokker-Planck equation.

Objective: To study the modality of multidisciplinary therapy and prognosis of cervical cancer patients with positive lymph nodes after radical surgery., Methods: From January 1990 to June 2003, 215 patients with clinical stage I b1-II b node-positive cervical carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy and were histologically confirmed to have lymph node involvement were analyzed. These patients were divided into four groups as chemoradiotherapy group (107 cases), radiotherapy group (45 cases), chemotherapy group (22 cases) and no adjuvant therapy group (41 cases). The prognosis and potential prognostic variables of the four groups were studied by survival analysis., Results: The 3-year disease-free survival (DFS) rate of the chemoradiotherapy group, chemotherapy group, radiotherapy group and no adjuvant therapy group were 60.7%, 53.5%, 47.4% and 36.0% respectively. The 3-year DFS rate of the chemoradiotherapy group was significantly higher than that of the no adjuvant therapy group (P = 0.001). However, the 3-year DFS rate of the chemotherapy group, radiotherapy group were not significantly higher than that of the no adjuvant therapy group (P = 0.060 and 0.159). Among the four groups, the pelvic recurrent rate of the chemoradiotherapy group (7.5%) was much lower than those of the other three groups (22.7%, 26.7%, 34.1%, respectively; P < 0.01). However, the distant metastases rate did not decrease significantly (16.8%, 18.2%, 15.6%, 22.0%, respectively; P > 0.05), neither did the distant metastasis with pelvic recurrent rate (P > 0.05). COX proportional hazard model analysis showed that tumor size, histological type, the number of positive lymph node and postoperative adjuvant therapy were independent survival predictors of the patients with positive lymph node (P < 0.05)., Conclusion: Chemoradiotherapy after radical surgery significantly improves the 3-year DFS, and decreases the pelvic recurrence in the cervical cancer patients with positive lymph node.

Background and Objectives: The study of pathology and prognosis for patients with ovarian tumors of low malignant potential (LMP) has been well documented. The treatment, particularly the secondary surgery, for recurrent disease is less documented. This study was conducted to investigate the role of secondary surgical cytoreduction for recurrent ovarian carcinoma of LMP., Methods: Patients with ovarian carcinoma of LMP at advanced stages experiencing disease recurrence and treated by secondary surgical cytoreduction at Fudan University Cancer Hospital were retrospectively reviewed., Results: Sixteen patients with recurrent serous and mucinous ovarian LMP tumors who underwent secondary surgical cytoreduction were entered in this study. The median age was 46.5 years. The 5-year survival in those with residual disease < or =1 cm after secondary surgical cytoreduction was 83%, compared to 26% in those with residual disease >1 cm (P = 0.01). Multivariate analysis suggested that extent of recurrent disease (solitary vs. multiple, relative risk [RR] =2.69, P < 0.01), and residual disease after secondary surgical cytoreduction (< or =1 cm vs. >1 cm, RR = 2.56, P < 0.01) were determinants of survival., Conclusions: For recurrent ovarian carcinomas of low malignant potential, prolonged survival was observed in patients with solitary recurrent disease and optimal secondary surgical outcome.

Objective: To evaluate the transposed ovarian function and complications in cervical cancer patients with postoperative pelvic radiotherapy., Methods: Sixty-two women with stage I-IIa cervical cancer were treated with radical hysterectomy and pelvic lymphadenectomy and transposition of both ovaries to paracolic gutters from 1997 to 2003 at the Cancer Hospital of Fudan University. Menopausal symptoms, levels of follicle-stimulating hormone (FSH) and E2 were evaluated to assess ovarian function., Results: Of 31 patients with stage IIa or poorly differentiated tumor or tumor > or = 2 cm in diameter, preoperative vaginal radiation was employed to deliver a dose of 15 Gy at point A. Postoperative pelvic radiation was performed in 15 patients. Totally 20% (6/30) of patients undergoing ovaries transposition without any radiation experienced ovarian failure within a mean of 15.7 months. In 35% (6/17) of patients with preoperative vaginal radiation, ovarian failure occurred within a mean of 12.0 months. When patients receiving postoperative pelvic radiation and ovaries transposition were considered together, 64% (9/14) experienced ovarian failure within a mean of 9.2 months (P < 0.05). Only 2 (3%) patients had cysts in transposed ovaries not requiring further surgery. There was no metastasis of the ovaries., Conclusions: Lateral ovarian transposition is safe to patients with early stage cervical cancer. Both pre- and post-operative radiation significantly damages the ovarian function. Even ovaries transposition procedure also reduces the effectiveness.

The interaction of Pb2+ and DNA of fish intestines was investigated using absorption spectrum, fluorescence emission spectrum, and electrophoresis. Ultraviolet absorption spectra indicated that with the addition of Pb2+, the DNA generated obvious hypochromic effect, and the absorption peak at 207 nm of DNA was blue-shifted. The fluorescence emission spectra showed that with the addition of Pb2+ , the emission peak of DNA at about 419 nm did not have obvious changes, but the intensity of fluorescence reduced gradually, showing that Pb2+ has quenching effect on the DNA endogenous fluorescence. Pb2+ has 0.8 binding sites to DNA, and the fluorescence quenching of DNA caused by Pb2+ belongs to static quenching. The binding constants of binding sites are 6.08 x 10(4) L x mol(-1) and 2.82 x 10(4) L x mol(-1) from the Lineweaver-Burk plot. The experiments of ultraviolet and fluorescence spectra showed that exogenous Pb2+ could cause some changes to the conformation of DNA, but analysis of electrophoresis proved that exogenous Pb2+ at different concentration did not result in DNA breakage.

Objective: To investigate individualized and multi-phase management of recurrent epithelial ovarian carcinoma in order to improve survival of the patients., Methods: From 1998 to 2002, 70 patients with recurrent epithelial ovarian carcinoma were enrolled in the present study. The treatments were divided into: (1) Induction of tumor remission: platinum sensitive patients were treated with paclitaxol + cisplatin (TP) or carboplatin + cyclophosphamide (CP) regimen; platinum resistant patients used Taxol + mitomycin (TM) or etoposide + mitomycin (VM) regimen. Resection of tumors was done in an attempt to reduce the residual tumor with a diameter less than 1 cm. Local radiotherapy was performed for those with residual tumor and who achieved clinical response after chemotherapy or surgery. (2) Consolidation therapy: chemotherapy with lower doses was administrated after disease remission. Interferon was used as immunotherapy during chemotherapy and radiotherapy. Survival analysis was done., Results: (1) The 1, 2, 3, 4, 5-year survival rates were 67%, 51%, 45%, 38%, 32%. Median survival was 38.57 months. (3) The 1, 2, 3-year progression-free survival rates of the research arm were 41%, 37%, 24%. Median progression-free survival was 12.00 months. (4) Multivariate analysis revealed that platinum-free interval (P < 0.05), Karnofsky performance scale (P < 0.01), residual disease (P < 0.01) and courses of second-line chemotherapy (P < 0.05) were independent prognostic factors. Residual disease (P < 0.05) and courses of second-line chemotherapy (P < 0.01) contributed to progression-free survival., Conclusions: Individualized and multi-phase treatment of recurrent epithelial ovarian carcinoma is efficacious. Optimal second cytoreduction and second-line chemotherapy are beneficial to improve the survival.

Background: This study was performed to address patient selection criteria and the role of secondary cytoreductive surgery (SCR) in patients with epithelial ovarian carcinoma (EOC) who had relapsed tumors after a progression-free interval > or = 3 months., Methods: One hundred seventeen patients with relapsed EOC after a clinical complete remission duration > or = 3 months who underwent SCR were entered on this prospective trial. Survival curves were generated using the Kaplan-Meier method, and statistical comparisons were performed using log-rank tests, logistic stepwise regression analyses, and a Cox stepwise regression model., Results: The median patient age at the time of relapse was 53 years (range, 20-78 years). The median survival was 22 months and the estimated 5-year survival rate for the entire cohort was 17.2%. Tumor was confined to a solitary site in 33 patients and to > or = 2 sites in 84 patients. After they underwent SCR, 11 patients were rendered macroscopically disease free, 61 patients had residual disease that measured < or = 1 cm in greatest dimension, and 45 patients had bulky intraabdominal residual disease. Survival was influenced by the extent of relapse disease (solitary site vs. multiple sites; P < 0.0001), the size of residual disease after SCR (0 cm vs. < or = 1 cm [P = 0.1211], < or = 1 cm vs. > 1 cm [P = 0.0002], and 0 cm vs. > 1 cm [P = 0.0011]), Eastern Cooperative Oncology Group performance status (0 vs. 1 [P = 0.134], 1 vs. 2 [P = 0.007], and 0 vs. 2 [P = 0.0012]), and the number of cycles of salvage chemotherapy (1-2 cycles vs. 3-5 cycles [P = 0.0144]; 1-2 cycles vs. > or = 6 cycles [P < 0.0001]; and 3-5 cycles vs. > or = 6 cycles [P = 0.0009]). The outcome of SCR was influenced by the extent of relapse disease (multiple sites [51.2%] vs. solitary sites [87.9%]; relative risk [RR] = 9.1237; P = 0.0002) and by the use of bowel resection (yes [60.9%] vs. no [37.5%]; RR = 0.3828; P = 0.0106)., Conclusions: SCR was found to be safe for patients with relapsed EOC who achieved a clinical complete remission that lasted > or = 3 months, with resectability similar to that of primary debulking surgery. Optimal surgical outcomes were achieved easily in patients who apparently had solitary tumor sites, with bowel resection making it possible to remove bulky tumors that involved the intestine. A survival benefit was provided by optimal SCR, particularly when surgery was supported by multiple courses of salvage chemotherapy., (Copyright 2004 American Cancer Society.)

Background & Objective: Pelvic lymph node metastasis was the important prognostic factor for the patients with cervical carcinoma. However, the relationship among the number of positive nodes, site of metastatic nodes, adjuvant therapy, and the prognosis were unknown. The purpose of this study was to investigate the variables that could predict the prognosis of the patients with stage Ib-IIb node-positive cervical carcinoma., Methods: Sixty-six patients with stage Ib-IIb cervical carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy were analyzed retrospectively. Potential prognostic variables were studied by Cox proportional hazard model., Results: The 5-year survival rate of the patients with pelvic lymph node metastasis was 40.7%. Cox proportional hazard model analysis showed cellular differentiation, number of positive nodes, and adjuvant therapy were the important prognostic factors (P< 0.05). The 5-year survival rate of patients with one positive node (56.5%) was higher than that (36.4%) of those with two or more positive nodes (P< 0.05). The former's distant metastatic rate (5.9%) was lower than the latter's (32.7%) (P=0.05). However, there was no difference of pelvic recurrence between them (P >0.05). The 5-year survival rate of the patients who had no adjuvant therapy (12.6%) was much lower than that (53.7%) of those with adjuvant therapy (P< 0.05). However, the differences of the effects among adjuvant radiotherapy, chemotherapy, and chemoradiotherapy were not obvious (P >0.05)., Conclusion: The prognosis of patients with stage Ib-IIb node-positive cervical carcinoma who underwent radical surgery was poor. Adjuvant therapy can improve the survival rate, decrease the pelvic recurrence and distant metastasis.

The objective of this paper is to clarify the role of cytoreductive surgery and salvage chemotherapy in the management of recurrent advanced epithelial ovarian carcinoma (RAEOC) and to identify factors affecting disease recurrence. One hundred sixty seven patients with RAEOC treated at the Cancer Hospital of Fudan University between January 1986 and December 1997 were retrospectively reviewed. Survival was calculated by Kaplan-Meier method with difference in survival estimated by the log-rank test. Independent prognostic factors were identified by the Cox stepwise regression model and variants associated with disease recurrence were determined using logistic stepwise regression methods. The median age was 52 (range 27-72) years. Sixty (35.9%) patients underwent re-debulking surgery, 23 of them with residual disease

The aim of this study was to investigate therapeutic efficacy of adenovirus-mediated E1a gene therapy for ovarian cancer in vitro and in vivo. Recombinant replication-deficient adenoviral vectors were prepared by superinfection of 293 cells, and then purified. The efficacy of the adenovirus vector system to infect ovarian cells was tested using different multiplicity of infection (MOI) and different times (1-4) of Ad.RSVlacZ. SKOV-3 cells (10(3) per well) were infected once with 2 x 10(4) adenovirus. The cells were harvested and counted on different days for 7 days to generate the in vitro growth curve. Tumor-bearing mice were injected intraperitoneally with ovarian cancer cells and treated by intraperitoneal injection of 100 microl (2.5 x 10(8) PFU) viral solution containing either replication-deficient Ad.E1a(+); control virus Ad.E1a(-) which is the same adenovirus as Ad.E1a(+) except for E1a deletion, or just phosphate buffered solution. The transduction efficacy increased with higher MOI and reached a plateau at the 20:1 ratio. When Ad.E1a(+) was used to transduce the HER-2/neu overexpressing human ovarian cancer cell line SKOV-3, tumor cell growth in vitro was greatly inhibited by E1a transduction. Also, Ad.E1a+ greatly inhibited tumor growth of SKOV-3-bearing mice. Immunohistochemistry analysis indicated that Ad.E1a protein was expressed in tumor tissue and expression of HER-2/neu p185 protein was suppressed. Very strong beta-gal staining was detected in tumors, and beta-gal activity in small intestine, lung, heart, stomach, liver, and kidney was detected. No beta-gal activity was detected in the tumor and other organs in control mice injected with Ad.E1a(-) or PBS. Adenovirus-type 5 E1a gene can efficaciously inhibit HER-2/neu-overexpressing ovarian cancer, and this promising procedure could greatly benefit ovarian cancer patients with high expression of HER-2/neu.

Aims: To investigate the impact on survival of secondary cytoreduction for advanced epithelial ovarian cancer and variables influencing redebulking surgical outcome., Methods: Between 1986 and 1997, 106 patients who received secondary cytoreductive surgery and consequent second-line chemotherapy for stages III and IV epithelial ovarian cancer were retrospectively reviewed. The optimal residual disease cut-off was 1.0 cm. The Cox proportional regression model and logistic stepwise regression were used in statistical processing of the data., Results: The median age of the patients was 50 years (range, 26-77 years). Optimal secondary cytoreduction was achieved in 46 of 106 patients (43.4%). There was a significant difference in survival between patients who were optimally cytoreduced compared to those suboptimaly cytoreduced, with an estimated median survival in the optimal group of 20 months vs 8 months in the suboptimal group ((2)=42.03, P=0.0000). When factorized, patients had significant survival benefit from optimal secondary cytoreduction for recurrent disease and interval cytoreduction. Survival was adversely influenced by progression-free interval < or =12 months (P=0.0078), residual disease >1 cm (P=0.0001) and presence of refractory ascites (P=0.0001). The probability of successful redebulking surgery was affected by presence of refractory ascites (P=0.0023) in all 106 patients and by the ascites (P=0.0072) and residual disease at initial operation in recurrent disease (P=0.0096)., Conclusion: Secondary surgical cytoreduction surgery significantly lengthened survival for patients with recurrent epithelial ovarian cancer or those receiving interval cytoreduction. Patients with refractory ascites, however, were not suitable for aggressive secondary surgery, and redebulking surgery for those with residual disease of >1.0 cm after primary operation should be considered prudently in recurrent disease., (Copyright 2000 Harcourt Publishers Ltd.)

Background and Objectives: The value of secondary cytoreductive surgery is still controversial, especially in patients with recurrent epithelial ovarian cancer. In this retrospective study, we investigated the effect on survival of secondary cytoreduction for recurrent disease and variables influencing redebulking surgical outcome., Methods: Between 1986 and 1997, 60 patients who received primary cytoreductive surgery and platinum-based chemotherapy for stage III and IV epithelial ovarian cancer experienced disease recurrence at least 6 months after completion of primary therapy, and secondary surgical cytoreduction was performed. The optimal residual disease cutoff was 1.0 cm. The Cox proportional regression model and Logistic stepwise regression were used in statistical processing of the data., Results: The median progression-free interval between the two operations was 13 months (range, 6-56 months). Optimal secondary cytoreduction was achieved in 23 patients (38.33%). There was a significant difference in survival between patients who were optimally cytoreduced compared to those suboptimally cytoreduced, with an estimated median survival in the optimal group of 19 months vs. 8 months in the suboptimal group (chi(2) = 22.04, P = 0.0000). Prognosis of survival for individuals with progression-free interval >12 months was better than that of those with the interval 1.0 cm after primary operation should be considered prudently., (Copyright 2000 Wiley-Liss, Inc.)

The purpose of this study was to investigate the clinical features of patients with epithelial ovarian cancer (EOC) that are initially categorized as extraabdominal adenocarcinoma of unknown primary. Twenty-five patients with EOC, who were treated in the Cancer Hospital of Shanghai Medical University from January 1986 to December 1997, and manifesting as extraperitoneal or liver parenchyma metastases at the time of presentation without detectable ovarian tumors, were retrospectively studied. Sixteen patients (64%) were optimally surgical debulked. When compared with 52 other women with stage IV EOC, 20 patients who initially sought treatment for extraabdominal metastases experienced a better prognosis, with an estimated median survival of 24 months versus 10 months (p = 0.0427). The median survival was 30 months in patients with pleural effusion or supraclavicular lymph node metastases versus 19 months in those with spread to other sites (p = 0.0264). The prognosis of such cases, mainly for those with supraclavicular lymphadenopathy or malignant pleural effusion, is better than that for other stage IV EOC patients, probably because most of the patients who initially had distant metastases were generally in condition that permitted aggressive surgery or multicycle chemotherapy.

We tried to determine the role of cytoreductive surgery for stage IV epithelial ovarian cancer and in what conditions this surgical procedure could carry the best benefits. From January 1986 to December 1997, seventy-one of 73 patients with stage IV epithelial ovarian cancer who were treated in Cancer Hospital of Shanghai Medical University were retrospectively reviewed. Clinical information including age, grade, histology, presence of ascites, size of residual disease, site of extra-abdominal metastasis, whether initially presenting as metastatic disease or not, neo-adjuvant chemotherapy, platinum-based chemotherapy and second-line chemotherapy was obtained. Survival was calculated by life-table and survival curves were computed using the Kaplan-Meier method with differences in survival estimated by log-rank test. Independent prognostic factors were identified by Cox's proportional hazards regression model. The median age of the patients' population was 54 years (range 22-82), median follow-up time was 12 months (range 3 to 130) and estimated 5-year survival rate 6.1%. Thirty out of 71 (42.3%) patients were successfully debulked (< or = 1 cm) at the time of initial surgery. There was a significant difference in five-year survival rate between patients optimally (14.1%) vs suboptimally (0%) cytoreduced, with an estimated median survival in the optimal group of 23 months vs 9 months in the suboptimal group (P=0.0001, long-rank test). When the variables were factorized, only in patients with malignant pleural effusion or positive supraclavicular lymph nodes, optimal cytoreduction could get the greatest benefits. Multivariate analysis revealed that the size of residual disease and ascites were independent factors of survival. However, only ascites was the prognostic factor of progression-free survival. Optimal cytoreductive surgery is an important determinant of survival in women with stage IV epithelial ovarian cancer, mainly in those with malignant pleural effusion or positive supraclavicular lymph node pathology.