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Wenxin Yao,1 Peicheng Xu,1 Zhiqing Pang,2,3 Jingjing Zhao,2,3 Zhilan Chai,2,3 Xiaoxia Li,4 Huan Li,2,3 Menglin Jiang,2,3 Hongbo Cheng,2,3 Bo Zhang,2,3 Nengneng Cheng4 1Shanghai Xuhui District Dental Center, 2Key Laboratory of Smart Drug Delivery, Ministry of Education, 3Department of Pharmaceutics, School of Pharmacy, Fudan University, 4Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China Background: Rapid local drug clearance of antimicrobials is a major drawback for the treatment of chronic periodontitis. In the study reported here, minocycline-loaded poly(ethylene glycol)-poly(lactic acid) nanoparticles were prepared and administered locally for long drug retention and enhanced treatment of periodontitis in dogs.Methods: Biodegradable poly(ethylene glycol)-poly(lactic acid) was synthesized to prepare nanoparticles using an emulsion/solvent evaporation technique. The particle size and zeta potential of the minocycline-loaded nanoparticles (MIN-NPs) were determined by dynamic light scattering and the morphology of the nanoparticles was observed by transmission electron microscopy. The in vitro release of minocycline from MIN-NPs and in vivo pharmacokinetics of minocycline in gingival crevice fluid, after local administration of MIN-NPs in the periodontal pockets of beagle dogs with periodontitis, were investigated. The anti-periodontitis effects of MIN-NPs on periodontitis-bearing dogs were finally evaluated.Results: Transmission electron microscopy examination and dynamic light scattering results revealed that the MIN-NPs had a round shape, with a mean diameter around 100 nm. The in vitro release of minocycline from MIN-NPs showed a remarkably sustained releasing characteristic. After local administration of the MIN-NPs, minocycline concentration in gingival crevice fluid decreased slowly and retained an effective drug concentration for a longer time (12 days) than Periocline®. Anti-periodontitis effects demonstrated that MIN-NPs could significantly decrease symptoms of periodontitis compared with Periocline and minocycline solution. These findings suggest that MIN-NPs might have great potential in the treatment of periodontitis. Keywords: minocycline, nanoparticles, periodontitis, local delivery

To assess whether post-hysterosalpingography evaluation was associated with pregnancy rate and to identify independent risk factors for pregnancy success after salpingostomy in patients with hydrosalpinx. A retrospective analysis was conducted on the clinical data of 47 patients diagnosed with hydrosalpingography (HSG) in our hospital from 2015 to 2018. These patients received laparoscopic surgery and another salpingography within 2 months after surgery. According to the fallopian tube conditions evaluated by HSG before and after surgery, the patients could be divided into two groups. According to the pregnancy rate and postoperative HSG of patients with hydrosalpinx after laparoscopy, the total pregnancy rate of the tubal improved group was 65.62%, while that of the non-improved group was 20%, with statistical significance ( p  < 0.05). We found that hysterosalpingography after salpingostomy in patients with hydrosalpinx can provide reference for clinical treatment and improve the prognosis of patients.

Objective: The objective of this review was to evaluate the efficacy of mental imagery training (MIT) in promoting bilateral transfer (BT) of motor performance for healthy subjects., Data Sources: We searched 6 online-databases (Jul-Dec 2022) using terms: "mental practice," "motor imagery training," "motor imagery practice," "mental training," "movement imagery," "cognitive training," "bilateral transfer," "interlimb transfer," "cross education," "motor learning," "strength," "force" and "motor performance.", Study Selection and Data Extraction: We selected randomized-controlled studies that examined the effect of MIT on BT. Two reviewers independently determined if each study met the inclusion criteria for the review. Disagreements were resolved through discussion and, if necessary, by a third reviewer. A total of 9 articles out of 728 initially identified studies were chosen for the meta-analysis., Data Synthesis: The meta-analysis included 14 studies for the comparison between MIT and no-exercise control (CTR) and 15 studies for the comparison between MIT and physical training (PT)., Results: MIT showed significant benefit in inducing BT compared to CTR (ES = 0.78, 95% CI = 0.57-0.98). The effect of MIT on BT was similar to that of PT (ES = -0.02, 95% CI = -0.15-0.17). Subgroup analyses showed that internal MIT (IMIT) was more effective (ES = 2.17, 95% CI = 1.57-2.76) than external MIT (EMIT) (ES = 0.95, 95% CI = 0.74-1.17), and mixed-task (ES = 1.68, 95% CI = 1.26-2.11) was more effective than mirror-task (ES = 0.46, 95% CI = 0.14-0.78) and normal-task (ES = 0.56, 95% CI = 0.23-0.90). No significant difference was found between transfer from dominant limb (DL) to non-dominant limb (NDL) (ES = 0.67, 95% CI = 0.37-0.97) and NDL to DL (ES = 0.87, 95% CI = 0.59-1.15)., Conclusion: This review concludes that MIT can serve as a valuable alternative or supplement to PT in facilitating BT effects. Notably, IMIT is preferable to EMIT, and interventions incorporating tasks that have access to both intrinsic and extrinsic coordinates (mixed-task) are preferred over those that involve only one of the two coordinates (mirror-task or normal-task). These findings have implications for rehabilitation of patients such as stroke survivors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yao, Ge, Zhang, Hemmat, Jiang, Liu, Lu, Yaghi and Yue.)

The Brother of Regulator of Imprinted Sites (BORIS, gene symbol CTCFL) has previously been shown to promote colorectal cancer cell proliferation, inhibit cancer cell apoptosis, and resist chemotherapy. However, it is unknown whether Boris plays a role in the progression of in situ colorectal cancer. Here Boris knockout (KO) mice were constructed. The function loss of the cloned Boris mutation that was retained in KO mice was verified by testing its activities in colorectal cell lines compared with the Boris wild-type gene. Boris knockout reduced the incidence and severity of azoxymethane/dextran sulfate-sodium (AOM/DSS)-induced colon cancer. The importance of Boris is emphasized in the progression of in situ colorectal cancer. Boris knockout significantly promoted the phosphorylation of γH2AX and the DNA damage in colorectal cancer tissues and suppressed Wnt and MAPK pathways that are responsible for the callback of DNA damage repair. This indicates the strong inhibition of colorectal cancer in Boris KO mice. By considering that the DSS-promoted inflammation contributes to tumorigenesis, Boris KO mice were also studied in DSS-induced colitis. Our data showed that Boris knockout alleviated DSS-induced colitis and that Boris knockdown inhibited the NF-κB signaling pathway in RAW264.7 cells. Therefore Boris knockout eliminates colorectal cancer generation by inhibiting DNA damage repair in cancer cells and relieving inflammation in macrophages. Our findings demonstrate the importance of Boris in the development of in situ colorectal cancer and provide evidence for the feasibility of colorectal cancer therapy on Boris., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Saliva is a noninvasive biofluid that contains the metabolic signature of severe periodontitis (SP, Stage IV and Grade C). Conductive polymer spray ionization mass spectrometry (CPSI-MS) was used to record a wide range of metabolites within a few seconds, making this technique a promising point-of-care method for the early detection of SP (Stage IV and Grade C). Saliva samples from 31 volunteers, consisting of 16 healthy controls (HC) and 15 patients with SP (Stage IV and Grade C), were collected to identify dysregulated metabolites. Twenty metabolites were screened out, including seven amino acids. Moreover, the results showed that amino acid metabolism is closely related to the development of periodontitis. The present study further confirmed that salivary metabolites in the oral cavity were significantly altered after plaque removal. These results suggest that the combination of CPSI-MS is a feasible tool for preclinical screening of SP (Stage IV and Grade C)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Liu, Ju, Yao, Yang and Qian.)

Caffeine is one of the most widely used psychostimulants in the world and possesses central excitative, anti-depressive, and neuroprotective properties. However, excessive ingestion or abuse of caffeine can lead to intoxication. Many toxic effects are attributed to oxidative damage, and nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical intracellular regulator of the oxidative stress response. Here, we investigated the neurotoxicity of caffeine in rat pheochromocytoma PC12 cells and zebrafish larvae. It was found that caffeine inhibited the viability of PC12 cells in a dose- and time-dependent manner. Furthermore, it induced PC12 cell apoptosis and elevated reactive oxygen species (ROS) production. Quantitative polymerase chain reaction (qPCR) and western blotting revealed that caffeine also inhibited the expression levels of Nrf2 mRNA and protein and its target genes (e.g., NADPH quinone oxidoreductase 1 [NQO1]). Furthermore, Nrf2 silencing attenuated the toxic effects of caffeine. In addition, zebrafish larvae were treated with different doses of caffeine. Behavioral experiments showed that a low dose of caffeine (0.05 to 0.3 mM) increased the average distance of movement and promoted excitation. Survivorship curves showed that caffeine (0.2 to 1.5 mM) caused lethality. Finally, qPCR revealed that a higher dose of caffeine inhibited mRNA levels in the Nrf2 pathway. Based on these results, this study identified for the first time that overuse of caffeine can induce neurotoxicity by inhibiting the Nrf2 pathway. These results will provide a new perspective for studies on caffeine toxicity., (© 2021 John Wiley & Sons, Ltd.)

To aim of the present paper was to introduce a novel fixation technique for the treatment of inferior pole fracture of the patella. We performed a prospective observational study of consecutive cases of inferior pole fracture of the patella that were treated at our institution between January 2018 and June 2019. The patients include three men and one woman, with an average age of 47 years (range: 42-59 years). All patients were treated with the novel rim plating fixation technique for preserving the inferior pole of the patella. During the surgery, a 2.4 mm straight locking compression plate was contoured to adapt to the arc of the lower half of the patella as the rim plate. After reduction of the fracture, the rim plate was fixed to the proximal fragment of the patella through multiple locking screws, against the continuous pull of the patellar tendon. The rim plate encircles and constricts the inferior pole fragments, functioning as a compression and blocking construct. If necessary, an additional anterior tension band or mini locking plate can be used to further prevent anterior displacement of the inferior pole fragments. Under this rigid fixation, motion of the knee and full weight-bearing were encouraged postoperatively. The patients were followed up monthly until 12 months after surgery. The time to achieve 90°pain-free, full range of motion of the knee, and fracture healing, were recorded. Related complications were monitored, including infection, loss of reduction, fixation failure, anterior knee pain, and soft-tissue irritation. The modified Cincinnati knee rating system was used for knee function assessment. The average operative time was 58.8 min (range: 52-63 min). The average blood loss was 59.8 mL (range: 45-71 mL). For all patients, pain-free 90° range of motion was restored in 2-4 weeks, and the full range of motion was restored in 8-11 weeks. All patients achieved bone union in 6-9 weeks with no displacement of the fragments or breakage of the implant. No patient complained of anterior knee pain or soft-tissue irritation. The modified Cincinnati score at 12-month follow up demonstrated excellent outcomes in all four patients. The rim plating technique may be a feasible option for the treatment of the inferior pole fracture of the patella., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Objective: This study aimed to explore the regulatory mechanism of miR-139-5p on the biological characteristics of breast cancer cells by targeting Collagen type XI alpha 1 chain (COL11A1). Method: GEO2R was used to identify the differentially expressed genes (DEGs) of breast cancer in GEO database. miRDB, miRanda and TargetScan databases were used to predict the miRNAs that regulate COL11A1. qRT-PCR was used to detect the expressions of COL11A1 and miR-139-5p in breast cancer cells, and western blot was used to detect the protein level of COL11A1. RNA binding protein immunoprecipitation assay was employed to test the targeted relationship between miR-139-5p and COL11A1, which was further verified by dual-luciferase reporter gene assay. CCK-8 assay was performed to detect the cell proliferation, and flow cytometry was carried out to examine the cell apoptosis. Moreover, western blot was used for the detection of caspase-3, Bax and Bcl-2 protein levels. Results: A total of five DEGs were screened from the GEO database, of which COL11A1 was the only highly expressed in breast cancer. According to the database analysis, we predicted that miR-139-5p was much likely to target the expression of COL11A1. MiR-139-5p was poorly expressed in breast cancer cells and targeted inhibited COL11A1. Silencing COL11A1 or overexpressing miR-139-5p both could inhibit the proliferation and promote the apoptosis, while overexpressing the two factors simultaneously could reverse such effect. Conclusion: Overexpression of miR-139-5p inhibits the proliferation and promotes the apoptosis of breast cancer cells by inhibiting the expression of COL11A1.

Objective: Whether lymph node dissection (LND) should be performed concomitantly with radical nephrectomy (RN) for non-metastatic renal carcinoma has still been controversial recently. We conducted a meta-analysis assessing oncologic outcomes of radical nephrectomy with lymph node dissection (LND) and without lymph node dissection (non-LND) in non-metastatic renal cell carcinoma (NMRCC)., Patients and Methods: A systematic review was performed until April 2018 using a comprehensive search in PubMed, EMBASE, and Cochrane Library databases to identify eligible comparative studies. A formal meta-analysis was performed for studies comparing radical nephrectomy with LND and radical nephrectomy with non-LND for cT1-T4NxM0 tumors. Furthermore, a subgroup analysis for locally advanced renal cell carcinoma (cT3-T4NxM0) was conducted., Results: Thirteen studies on patients with LND and non- LND were identified and included in the analysis. LND group did not have a significantly better survival than non-LND group for cT1-T4NxM0 tumors (HR 0.93, 95% CI 0.78-1.11, p=0.45), However, in the subgroup of locally advanced renal cell carcinoma (cT3-T4NxM0), it showed a significantly better OS rate in patients who had undergone LND compared to those without LND (HR 0.73, 95% CI 0.60-0.90; p=0.003)., Conclusions: LND offers better cancer control and better long-term survival in locally advanced renal cell carcinomas (cT3-T4NxM0). This conclusion should be confirmed by a prospective randomized clinical trial.

Objective: Holliday junction-recognizing protein (HJURP) was found to be upregulated in several tumors, including non-small cell lung cancer (NSCLC), and the effect of HJURP on NSCLC remains unknown. The objective of the present study was to explore the clinical significance of HJURP and its function in regulating the progression of NSCLC., Patients and Methods: Reverse Transcriptions-Polymerase Chain Reaction (RT-PC) and Western blot were performed to detect the expression levels of HJURP in NSCLC tissues and cell lines. The association of HJURP expression level with various important clinicopathological parameters was evaluated. Then, the effects of HJURP expression on tumor cell behavior in vitro were analyzed by the Cell Counting Kit-8 (CCK-8), EdU assays, colony formation, flow cytometry, and transwell assays. The protein levels of related proteins of the Wnt/β-catenin pathway were determined using the Western blot assay., Results: Our study showed that HJURP was significantly upregulated in both NSCLC tissues and cell lines. The higher expression of HJURP was associated with advanced TNM stage, distant metastasis, and poor prognosis. Our data from in vitro assays confirmed that the knockdown of HJURP suppressed NSCLC cells proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) progress, and induced cells apoptosis. Notably, through Western blot analysis, we found that HJURP suppression remarkably decreased β-catenin, cyclin D1 and c-myc expression level in NSCLC cell lines., Conclusions: Our findings provide clues regarding the role of HJURP as a tumor promoter in NSCLC via the activation of the Wnt/β-catenin pathway, indicating HJURP may be a promising therapeutic target for NSCLC.

Halomonas has been developed as a platform for the next generation industrial biotechnology allowing open and nonsterile growth without microbial contamination under a high-salt concentration and alkali pH. To reduce downstream cost associated with continuous centrifugation and salt containing wastewater treatment, Halomonas campaniensis strain LS21 was engineered to become self-flocculating by knocking out an etf operon encoding two subunits of an electron transferring flavoprotein in the predicted electron transfer chain. Self-flocculation could be attributed to the decrease of the surface charge and increase of the cellular hydrophobicity resulted from deleted etf. A wastewaterless fermentation strategy based on the self-flocculating H. campaniensis was developed for growth and the production of poly-3-hydroxybutyrate (PHB) as an example. Most microbial cells flocculated and precipitated to the bottom of the bioreactor within 1 min after stopping the aeration and agitation. The supernatant can be used again without sterilization or inoculation for the growth of the next batch after collecting the precipitated cell mass. The wastewaterless process was conducted for four runs without generating wastewater. PHB accumulation by the self-flocculent strain was enhanced via promoter and ribosome binding site optimizations, the productivities of cell dry weight and PHB were increased from 0.45 and 0.18 g·L -1 ·hr -1 for the batch process compared to 0.82 and 0.33 g·L -1 ·hr -1 for the wastewaterless continuous process, respectively. This has clearly demonstrated the advantages of the wastewaterless process in that it not only reduces wastewater but also increases cell growth and product formation efficiency in a given period of time., (© 2018 Wiley Periodicals, Inc.)

Objective: Brain injury is implicated in pathogenesis of postoperative delirium (POD) and cognitive dysfunction (POCD). S100A12 is involved in inflammatory process and is recently known as a biomarker for brain injury. Herein, we clarified whether serum S100A12 levels are related to POD and POCD after hip fracture surgery in elderly patients., Materials and Methods: In this prospective, observational study, we gauged S100A12 levels in preoperative and postoperative serum from 186 patients and serum from 186 controls. Patients were categorized according to the presence of POD and POCD., Results: Postoperative, but not preoperative serum S100A12 levels were significantly higher in patients than in controls. There was a positive and independent correlation between postoperative C-reactive protein and S100A12 levels (t = 8.797, p < 0.001). Postoperative S10012 levels and age were independently associated with the risk of developing POD (S100A12 levels: odds ratio [OR] = 1.166, 95% confidence interval [CI] = 1.045-2.087, p = 0.001; age: OR = 1.243, 95% CI = 1.073-1.419, p = 0.012) and POCD (S100A12: OR = 1.157, 95% CI = 1.030-1.986, p = 0.003; age: OR = 1.228, 95% CI = 1.054-1.387, p = 0.014). In terms of area under receiver operating characteristic curve, postoperative S100A12 levels had a higher predictive ability than age and their combination dramatically exceeded that of each one alone., Conclusions: Postoperative elevated serum S100A12 levels have a strong relation to inflammation and are associated independently with the development of POD and POCD, substantializing serum S100A12 as a potential biomarker for predicting POD and POCD in elderly patients undergoing hip fracture surgery., (© 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Diabetes mellitus is a major cause to induce osteoporosis. Though the pathogenesis of osteoporosis progression has been well investigated, its still not fully understood. Recently, cereblon (CRBN) was considered as a negative modulator of adenosine monophosphate-activated protein kinase (AMPK) in vitro and in vivo. Here, we presented results indicating that CRBN could effectively regulate osteoporosis development. In STZ-induced wild type (WT) mice with diabetes, the osteoclasts were highly increased along with the deterioration of bone structure. However, CRBN knockout (KO) reduced blood glucose the levels and attenuated insulin resistance. What's more, CRBN ablation suppressed osteoclast differentiation and rescued diabetic bone loss in vivo, accompanied with decreased receptor activator of NF-kB ligand (RANKL), RANKL/osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRAP) levels, as well as improved AMP-activated kinase (AMPK) α/acetyl-CoA carboxylase (ACC)αactivation. In vitro, suppressing CRBN expression could reduce RANKL-induced osteoclastogenesis, supported by the reduction of TRAP-positive cells. CRBN knockdown (KD) obviously reduced RANKL-induced activity of IκBα/nuclear factor-κB (NF-κB) pathway. In addition, osteoclast-specific genes expression levels stimulated by RANKL were also decreased by CRBN silence. More importantly, CRBN blockage increased phosphorylated AMPK-α and ACC-α expressions in RANKL-incubated cells. However, these processes could be abolished by suppressing AMPK-α with its inhibitor, Compound C. Collectively, our data suggested that CRBN is a potential treatment option against diabetes-induced osteolytic bone disease., (Copyright © 2018. Published by Elsevier Inc.)

The network meta-analysis was conducted to compare the short-term efficacy of different single-drug targeted therapies in the treatment of renal cell carcinoma (RCC). We initially searched databases for randomized controlled trials (RCTs) on different single-drug targeted therapies in treating RCC. The meta-analysis combined the direct and indirect evidence to calculate the pooled odds ratios (OR) and draw surface under the cumulative ranking curves (SUCRA). A total of 14 eligible RCTs were ultimately selected. The partial response (PR) of Cabozantinib in the treatment of RCC was better than Sunitinib (OR = 2.7, 95%CI = 1.0-7.8), Everolimus (OR = 8.1, 95%CI = 3.1-25.0), and Temsirolimus (OR = 4.8, 95%CI = 1.0-31.0); the overall response rate (ORR) of Cabozantinib was better than Sorafenib, Sunitinib, Everolimus, and Temsirolimus (OR = 5.5, 95%CI = 1.1-27.0; OR = 2.6, 95%CI = 1.1-6.6; OR = 8.3, 95%CI = 3.5-20.0; OR = 5.7, 95%CI = 1.3-28.0 respectively). In addition, as for complete response (CR), PR, stable disease (SD), progressive disease (PD), ORR, and disease control rate (DCR), Cabozantinib had the best short-term efficacy among nine single-drug targeted therapies in the treatment of RCC (CR: 50.3%; PR: 93.6%; SD: 75.1%; PD: 68.0%; ORR: 95.5%; DCR: 73.2%); while Everolimus had the worst short-term efficacy (CR: 33.6%; PR: 22.3%; SD: 78.0%; PD: 35.9%; ORR: 22.9%; DCR: 19.9%). Our network meta-analysis indicated that Cabozantinib might have better short-term efficacy than other regimens in the treatment of RCC, while Everolimus might have poor short-term efficacy., (© 2017 The Author(s).)

β-Amyloid protein (Aβ) is thought to cause neuronal loss in Alzheimer's disease (AD). Aβ treatment promotes the re-activation of a mitotic cycle and induces rapid apoptotic death of neurons. However, the signaling pathways mediating cell-cycle activation during neuron apoptosis have not been determined. We find that Wnt5a acts as a mediator of cortical neuron survival, and Aβ 42 promotes cortical neuron apoptosis by downregulating the expression of Wnt5a. Cell-cycle activation is mediated by the reduced inhibitory effect of Wnt5a in Aβ 42 treated cortical neurons. Furthermore, Wnt5a signals through the non-canonical Wnt/Ca 2+ pathway to suppress cyclin D1 expression and negatively regulate neuronal cell-cycle activation in a cell-autonomous manner. Together, aberrant downregulation of Wnt5a signaling is a crucial step during Aβ 42 induced cortical neuron apoptosis and might contribute to AD-related neurodegeneration.

We performed a pooled analysis of the efficacy of serum neuron-specific enolase (NSE) levels for early detection of small cell lung cancer (SCLC) in patients with benign lung diseases and healthy individuals. Comprehensive searches of several databases through September 2016 were conducted. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Ultimately, 33 studies containing 9546 samples were included in the review. Pooled sensitivity of NSE for detecting SCLC was 0.688 (95%CI: 0.627-0.743), specificity was 0.921 (95%CI: 0.890-0.944), positive likelihood ratio was 8.744 (95%CI: 6.308-12.121), negative likelihood ratio was 0.339 (95%CI: 0.283- 0.405), diagnostic odds ratio was 25.827 (95%CI: 17.490- 38.136) and area under the curve was 0.88 (95%CI: 0.85- 0.91). Meta-regression indicated that study region was a source of heterogeneity in the sensitivity and joint models, while cut-off level was a source in the joint model. Subgroup analysis showed that enzyme linked immunosorbent assays had the highest sensitivity and radioimmunoassay assays had the highest specificity. The diagnostic performance was better in Europe [sensitivity: 0.740 (95%CI: 0.676-0.795), specificity: 0.932 (95%CI: 0.904-0.953)] than in Asia [sensitivity: 0.590 (95%CI: 0.496- 0.678), specificity: 0.901 (95%CI: 0.819-0.948)]. In Europe, 25 ng/ml is likely the most suitable NSE cut-off level. NSE thus has high diagnostic efficacy when screening for SCLC, though the efficacy differs depending on study region, assay method and cut-off level. In the clinic, NSE measurements should be considered along with clinical symptoms, image results and histopathology., Competing Interests: CONFLICTS OF INTEREST There is no conflicts of interest for any author regarding the publication of this manuscript.

Autophagy is a protective and life-sustaining process in which cytoplasmic components are packaged into double-membrane vesicles and targeted to lysosomes for degradation. Accumulating evidence supports that autophagy is associated with several pathological conditions. However, research on the functional cross-links between autophagy and disease genes remains in its early stages. In this study, we constructed a disease-autophagy network (DAN) by integrating known disease genes, known autophagy genes and protein-protein interactions (PPI). Dissecting the topological properties of the DAN suggested that nodes that both autophagy and disease genes (inter-genes), are topologically important in the DAN structure. Next, a core network from the DAN was extracted to analyze the functional links between disease and autophagy genes. The genes in the core network were significantly enriched in multiple disease-related pathways, suggesting that autophagy genes may function in various disease processes. Of 17 disease classes, 11 significantly overlapped with autophagy genes, including cancer diseases, metabolic diseases and hematological diseases, a finding that is supported by the literatures. We also found that autophagy genes have a bridging role in the connections between pairs of disease classes. Altogether, our study provides a better understanding of the molecular mechanisms underlying human diseases and the autophagy process.

Objectives: To evaluate the efficacy and safety of carboplatin-based preoperative chemotherapy in triple-negative breast cancer patients (TNBC)., Methods: PubMed, EMBASE, the Web of Science, the Cochrane Library, major clinical trial registries, and abstract collections from major international meetings were systematically searched for relevant randomized controlled trials. Endpoints included rates of pathologic complete response (pCR), overall response (ORR), breast-conserving surgery (BCS) and toxicity. Pooled relative risk (RR) was calculated for each endpoint using a fixed- or random-effect model depending on the heterogeneity among included studies., Results: A total of 5 randomized controlled trials involving 1007 patients were included in the meta-analysis. Carboplatin-based chemotherapy was associated with a pooled pCR rate of 53.3%, which was significantly higher than the rate associated with non-carboplatin therapy (37.8%, RR: 1.41, 95% confidence interval [CI]: 1.23 to 1.62, p less than 0.00001). Compared with non-carboplatin therapy (48.1%), carboplatin-based chemotherapy increased BCS rate (59.7%, RR: 1.24, 95%CI: 1.06 to 1.46, p=0.007). Carboplatin-based chemotherapy was associated with similar ORR as non-carboplatin therapy. Carboplatin-based chemotherapy was associated with higher incidence of grade 3 or 4 anemia, neutropenia, febrile neutropenia, and thrombocytopenia than non-carboplatin therapy, while the 2 regimens were associated with similar incidence of fatigue, leucopenia, and nausea/vomiting., Conclusion: The available evidence suggests that carboplatin-based preoperative chemotherapy is associated with significantly better pCR and BCS rates than non-carboplatin-based therapy in TNBC patients.

Previous studies in other provinces of China (Beijing, Xinjiang, Shanxi, Jiangxi, Shanghai, Guangdong, and Taiwan) suggest that the distributions of lymphoma subtypes differ compared with Western populations. In order to evaluate the characteristics of malignant lymphoma in Sichuan, China, we analyzed case series data from incident lymphoma patients diagnosed in 2008 from three hospitals, including a total of 1629 cases and including only current residents of Sichuan. The median age of diagnosis for cases was 54 years, with a higher proportion of male cases compared with female cases. The most commonly diagnosed subtypes included diffuse large B-cell lymphoma (40.4%), NK/T-cell lymphoma (NKTCL; 11.8%), mixed cellularity Hodgkin lymphoma (7.0%), mantle cell lymphoma (4.8%), and marginal zone B-cell lymphoma (3.9%). Differences in demographic characteristics between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) cases were apparent for median age at diagnosis (HL: 34 years; NHL: 57 years), and NHLs accounted for nearly all (99.3%) of the 931 cases of extranodal lymphoma. These findings indicate a higher proportion of NKTCL cases and a lower proportion of follicular lymphoma cases (2.3%) in these hospitals in Sichuan, relative to reports from some other provinces within China (e.g., Shanghai and Shanxi) and the USA. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Previous studies report greater activation in the cortical motor network in controlling eccentric contraction (EC) than concentric contraction (CC) of human skeletal muscles despite lower activation level of the muscle associated with EC. It is unknown, however, whether the strength of functional coupling between the primary motor cortex (M1) and other involved areas in the brain differs as voluntary movements are controlled by a network of regions in the primary, secondary and association cortices. Examining fMRI-based functional connectivity (FC) offers an opportunity to measure strength of such coupling. To address the question, we examined functional MRI (fMRI) data acquired during EC and CC (20 contractions each with similar movement distance and speed) of the right first dorsal interosseous (FDI) muscle in 11 young (20-32 years) and healthy individuals and estimated FC between the M1 and a number of cortical regions in the motor control network. The major findings from the mechanical and fMRI-based FC analysis were that (1) no significant differences were seen in movement distance, speed and stability between the EC and CC; (2) significantly stronger mean FC was found for CC than EC. Our finding provides novel insights for a better understanding of the control mechanisms underlying voluntary movements produced by EC and CC. The finding is potentially helpful for guiding the development of targeted sport training and/or therapeutic programs for performance enhancement and injury prevention.

Chemotherapy drugs such as vincristine (VCR) can cause neuropathic pain, and there is still lack of ideal strategy to treat it. The current study was designed to investigate effect of matrine (MT) on VCR-induced neuropathic pain in animal model. VCR (75 μg/kg, i.p. for 10 consecutive days) was administered to induce painful neuropathy model in mice. MT (15, 30 and 60 mg/kg, i.p.) and pregabalin (10 mg/kg, i.p.) were administered for 11 consecutive days. Various tests were performed to assess the degree of pain at different days (1, 6, 11, 16, and 21). Von Frey hair, hot plate, cold-plate and paw pressure tests were conducted to assess the degree of mechanical allodynia, thermal hyperalgesia, cold allodynia and mechanical hyperalgesia in the hind paw respectively. The electrophysiological and histopathological changes were also analyzed. Furthermore, tissue malondialdehyde (MDA), total antioxidant capacity (T-AOC),superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total calcium (TCA), myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) were measured to investigate possible involvement of MT in inflammation and oxidative stress. Administration of MT attenuated the VCR-induced behavioral alterations as well as electrophysiological and histopathological changes in a dose dependent manner. Further, MT also attenuated the VCR-induced oxidative stress (MDA, T-AOC, GSH-Px, SOD and TCA) and inflammation (MPO, TNF-α, IL-6 and IL-10). Taken together, MT ameliorated VCR-induced painful neuropathy, which might be attributed to neuroprotective effects by subsequent reduction in oxidative stress and anti-inflammatory actions.

We conducted a pooled analysis comparing the efficacy of an immunohistochemistry (IHC) assay using the D5F3 antibody with that of fluorescence in situ hybridization (FISH) for detecting ALK gene rearrangement in NSCLC patients. A total of 32 studies involving 5805 samples were included in this review. Pooled sensitivity for D5F3 IHC was 0.97 (95%CI: 0.93-0.98), specificity was 0.99 (95%CI: 0.98-1.00), PLR was 119.20 (95%CI: 57.79-245.89), NLR was 0.03 (95%CI: 0.02-0.07), DOR was 3526.66 (95%CI: 1344.71-9249.03), and AUROC was 1.00 (95%CI: 0.99-1.00). Meta-regression revealed that specimen type was a source of heterogeneity for specificity, and specimen type and FISH signal distance were sources of heterogeneity in the joint model. Subgroup analysis revealed that sensitivity and specificity were higher when the FISH signal distance standard was ≥ 2 than when it was ≥ 1. Sensitivity was higher for tumor specimens than for cell specimens; specificity was higher for cell specimens than for tumor specimens. In conclusion, the D5F3 IHC assay was nearly as effective as FISH for detection of ALK gene rearrangement in NSCLC patients.

Background: Bisphosphonates have exhibited anti-tumor activity in non-small cell lung cancer (NSCLC). We aimed to evaluate whether the combination of bisphosphonates with tyrosine kinase inhibitors of EGFR (EGFR-TKIs) could obtain a synergistic effect on advanced NSCLC patients with EGFR mutations., Methods: Between January 2008 and October 2013, 114 advanced EGFR mutations NSCLC patients who received EGFR-TKIs as first-line therapy were recruited from two cancer centers. Patients were separated into EGFR-TKIs alone or EGFR-TKIs plus bisphosphonates (combination) group. Median progression free survival (mPFS), median overall survival (mOS) distributions and survival curves were analyzed., Results: Among the 114 patients, 62 had bone metastases (19 patients treated with EGFR-TKIs, 43 patients treated with EGFR-TKIs + bisphosphonates). Median PFS and OS were significantly improved in combination group compared with EGFR-TKIs group (mPFS: 15.0 vs 7.3 months, P = 0.0017; mOS: 25.2 vs 10.4 months, P = 0.0015) in patients with bone metastases. Among the 71 patients (19 patients with bone metastases) treated with EGFR-TKIs alone, patients with bone metastases had poor survival prognosis (mPFS:7.3 vs 12.1 months, P = 0.0434; mOS:10.4 vs 22.0 months, P = 0.0036). The survival of patients with bone metastases who received EGFR-TKIs plus bisphosphonates therapy was non-inferior to patients without bone metastases treated with EGFR-TKIs alone (mPFS: 15.0 vs 12.1 months, p = 0.1871; mOS: 25.2 vs 22.0 months, p = 0.9798)., Conclusions: Concomitant use of bisphosphonates and EGFR-TKIs improves therapeutic efficacy and brings survival benefits to NSCLC patients with EGFR mutation and bone metastases.

Recent research on bilateral transfer suggests that imagery training can facilitate the transfer of motor skill from a trained limb to that of an untrained limb above and beyond that of physical practice. To further explore this effect, the present study examined the influence of practice duration and task difficulty on the extent to which imagery training and physical training influences bilateral transfer of a sequential key pressing task. In experiment 1, participants trained on the key pressing task using their non-dominant arm under one of three conditions (physical practice, imagery practice, and no practice). In a subsequent bilateral transfer test, participants performed the sequential task using their untrained dominant arm in either an original order or mirror-ordered sequence. In experiment 2, the same procedures were followed as in experiment 1 except that participants trained with their dominant arm and performed the bilateral transfer task with their non-dominant arm. Results indicated that with extended practice beyond what has been employed in previous studies, physical practice is more effective at facilitating bilateral transfer compared to training with imagery. Interestingly, significant bilateral transfer was only observed for transfer from the non-dominant to the dominant arm with no differences observed between performing the task in an original or mirror ordered sequence. Overall, these findings suggest that imagery training may benefit bilateral transfer primarily at the initial stages of learning, but with extended training, physical practice leads to larger influences on transfer.

Background: During radiotherapy for breast cancer, patients are greatly affected by pain, infection, and delayed healing of wounds caused by radiodermatitis. In the present study, we aimed to determine the efficacy of Liu-He-Dan in treating radiodermatitis., Methods: In 26 breast cancer patients who experienced moist decrustation while receiving radiotherapy, 5 g Liu-He-Dan was applied externally once daily after the wound surface had been cleaned and dried. The healing time was recorded, and a Kaplan-Meier survival curve was applied to analyze the treatment course. Meanwhile, a pain assessment using the Numeric Rating Scale (nrs) recorded the pain level experienced by patients after application of the Liu-He-Dan., Results: After application of Liu-He-Dan, the average healing time for the surface of the moist decrustation wounds was 14.17 ± 2.03 days (range: 5-22 days). Inflammatory seepage decreased significantly and exudation almost disappeared in 3 days. The pain trend line indicated that the average nrs score declined with treatment in all patients. The average nrs scores at days 1, 4, and 7 were 6.13, 3.62, and 2.58 respectively. After 3 days of treatment, pain was remarkably alleviated in 80.76% of patients. After treatment for 1 week, the pain remission rate was 96.15%, without any obvious adverse reactions., Conclusions: Liu-He-Dan was efficacious in treating radiation skin injury with little toxicity and few side effects; the economic efficiency of the treatment was also favourable. The Liu-He-Dan was generally well tolerated by patients. In future, randomized control trials will be established for further observation of the value of Liu-He-Dan in treating radiodermatitis in breast cancer.

Oxymatrine (OMT), an active constituent of Chinese herb Sophora flavescens Ait, has been proved to possess anti-tumor, anti-oxidant, anti-inflammatory, and anti-apoptotic activities. Previous study has demonstrated that OMT had protective roles on multiple in vitro and in vivo brain injury models including regulation of apoptosis-related proteins caspase-3, Bax and Bcl-2. In this study, we investigated whether this protective effect could apply to neonatal hypoxic-ischemic brain damage. Seven-day-old Sprague-Dawley rats were treated with the left carotid artery ligation followed by exposure to 8% oxygen (balanced with nitrogen) for 2.5 h at 37 °C. In sham group rats, neither ligation nor hypoxia was performed. After two successive days intraperitoneal injection with OMT (30, 60 and 120 mg/kg), Nimodipine (1 mg/kg), and saline, brain infarct volume was estimated, histomorphology changes were performed by hematoxylin-eosin (HE) staining as well as electron microscopy. In addition, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC), as well as production of malondialdehyde (MDA) were assayed in ipsilateral hemisphere homogenates to evaluate the redox status after hypoxic-ischemic. Expression of apoptosis-related proteins Caspase-3, Bax and Bcl-2 in brain were analyzed by western-blot analysis and immunofluorescence. Administration of OMT significantly decreased brain infarct volume and the percentage of injured cells, and ameliorated histopathology and morphological injury as well. Furthermore, OMT obviously increased the activities of SOD, GSH-Px, CAT and T-AOC, and decreased MDA content. Western-blot analysis showed a marked decrease in Caspase-3 expression and increase in the ratio of Bcl-2/Bax after OMT (120 mg/kg) post-treatment as compared with hypoxic-ischemic group. These results suggest that OMT exerts a neuroprotective effect against hypoxic-ischemic brain damage in neonatal rats, which is likely to be mediated through increasing anti-oxidant enzyme activities and inhibiting cell death., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Microglia‑mediated neuroinflammation is key in the pathogenesis of Alzheimer's disease (AD). Several studies have suggested that NADPH oxidase contributes to microglia‑mediated neuroinflammation. Resveratrol, which is a natural polyphenolic compound, exerts neuroprotective effects in AD due to its anti‑inflammatory properties. The present study aimed to investigate the effects of resveratrol on the activation of oligomeric amyloid β (oAβ)‑induced BV‑2 microglia, and to determine the role of NADPH oxidase in these effects. Microglial proliferation was measured by high‑content screening cell counting and using a bromodeoxyuridine incorporation assay. In addition, the levels of reactive oxygen species (ROS), nitric oxide (NO), tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β were assessed. The results of the present study demonstrated that resveratrol inhibited the proliferation of oAβ‑induced microglia and the production of pro‑inflammatory factors, including ROS, NO, TNF‑α and IL‑1β. Subsequent mechanistic investigations demonstrated that resveratrol inhibited the oAβ‑induced mRNA and protein expression levels of p47phox and gp91phox. These results suggested that NADPH oxidase may be a potential target for AD treatment, and resveratrol may be a valuable natural product possessing therapeutic potential against AD.

Enhanced activation in the non-lesion hemisphere in stroke patients was widely observed during movement of the affected upper limb, but its functional role related to motor planning and execution is still unknown.This study was to characterize the activation in the non-lesion hemisphere during movement planning and execution by localizing sources of high-density electroencephalography (EEG) signal and estimating the source strength (current density [A/m]).Ten individuals with chronic stroke and shoulder/elbow coordination deficits and 5 healthy controls participated in the study.EEG (64 channels) was recorded from scalp electrodes while the subjects performed a reach task involving shoulder flexion and elbow extension of the affected (patients) or dominant (controls) upper extremity. Sources of the EEG were obtained and analyzed at 17 time points across movement preparation and execution phases. A 3-layer boundary element model was overlaid and used to identify the brain activation sources. A distributed current density model, low-resolution electromagnetic tomography (LORETA) L1 norm method, was applied to the data pre-processed by independent component analysis.Subjects with stroke had stronger source strength in the sensorimotor cortices during the movement compared with the controls. Their contralesional/lesional activation ratio (CTLR) for the primary motor cortices was significantly higher than that of the controls during the movement-planning phase, but not during the execution phase. The CTLR was higher in planning than in the execution phase in the stroke group.Excessive contralesional motor cortical activation appears to be more related to movement preparation rather than execution in chronic stroke.

Purpose: Husband, as an important member of the family, greatly impacts the treatment decision. In this study, we sought to evaluate the attitudes toward breast conserving surgery (BCS) in Chinese breast cancer patients' husbands and explore the influencing factors., Methods: A self-structured questionnaire was distributed to the husbands of 1600 wives with breast cancer, eliciting information on their general information, the level of understanding of BCS, attitudes toward BCS and affecting reasons., Results: In all, 1468 (91.8%) husbands completed the questionnaire. Collation of the responses showed that only 3.0% had a good understanding of BCS and 81.5% did not favor BCS. Patients' husbands perception were associated with their age, religion, occupation, educational background, method of payment of medical expenses, understanding the disease condition and doctor's recommendations (p<0.05). The top reason was "fear of incomplete resection, which could easily lead to recurrence and metastasis"., Conclusions: This study indicates that Chinese husbands have skepticism and lack comprehensive and correct understanding for BCS. Meanwhile, their desire of obtaining knowledge was not strong. The results suggest a need for fundamental changes in husbands' education to ensure that they are able to obtain enough information so that they can help their wives make educated decisions.

Previous studies report greater activation in the cortical motor network in controlling eccentric contraction (EC) than concentric contraction (CC) despite lower muscle activation level associated with EC vs. CC in healthy, young individuals. It is unknown, however, whether elderly people exhibiting increased difficulties in performing EC than CC possess this unique cortical control mechanism for EC movements. To address this question, we examined functional magnetic resonance imaging (fMRI) data acquired during EC and CC of the first dorsal interosseous (FDI) muscle in 11 young (20-32 years) and 9 old (67-73 years) individuals. During the fMRI experiment, all subjects performed 20 CC and 20 EC of the right FDI with the same angular distance and velocity. The major findings from the behavioral and fMRI data analysis were that (1) movement stability was poorer in EC than CC in the old but not the young group; (2) similar to previous electrophysiological and fMRI reports, the EC resulted in significantly stronger activation in the motor control network consisting of primary, secondary and association motor cortices than CC in the young and old groups; (3) the biased stronger activation towards EC was significantly greater in the old than the young group especially in the secondary and association cortices such as supplementary and premotor motor areas and anterior cingulate cortex; and (4) in the primary motor and sensory cortices, the biased activation towards EC was significantly greater in the young than the old group. Greater activation in higher-order cortical fields for controlling EC movement by elderly adults may reflect activities in these regions to compensate for aging-related impairments in the ability to control complex EC movements. Our finding is useful for potentially guiding the development of targeted therapies to counteract age-related movement deficits and to prevent injury.

This study examined the characteristics of bilateral transfer of learning to control timing and fine force from a dominant limb to a nondominant limb. 20 right-handed college students (12 women, 8 men; M age = 21.5 yr., SD = 2.3) learned a sequential task consisting of timing and force control. Each participant completed a pre-test of the task with both hands and then performed 100 practice trials with the dominant hand. A post-test was conducted 1 hr. later. The results showed that after training, participants learned to control the timing and force. Nevertheless, only the time-control learning was transferred to the untrained hand, whereas the force-control learning did not transfer to the untrained hand.

Rhubarb is well known in traditional Chinese medicines (TCMs) mainly due to its effective purgative activity. Anthraquinones, including anthraquinone derivatives and their glycosides, are thought to be the major active components in rhubarb. To improve the quality control method of rhubarb, we studied on the extraction method, and did qualitative and quantitative analysis of widely used rhubarbs, Rheum tanguticum Maxim. ex Balf. and Rheum palmatum L., by HPLC-photodiode array detection (HPLC-DAD) and HPLC-mass spectrum (HPLC-MS) on a Waters SymmetryShield RP18 column (250 mm × 4.6 mm i.d., 5 μm). Amount of five anthraquinones was viewed as the evaluating standard. A standardized characteristic fingerprint of rhubarb was provided. From the quantitative analysis, the rationality was demonstrated for ancestors to use these two species of rhubarb equally. Under modern extraction methods, the amount of five anthraquinones in Rheum tanguticum Maxim. ex Balf. is higher than that in Rheum palmatum L. Among various extraction methods, ultrasonication with 70% methanol for 30 min is a promising one. For HPLC analysis, mobile phase consisted of methanol and 0.1% phosphoric acid in water with a gradient program, the detection wavelength at 280nm for fingerprinting analysis and 254 nm for quantitative analysis are good choices., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The purpose of this study was to compare the effect of training using internal imagery (IMI; also known as kinesthetic imagery or first person imagery) with that of external imagery (EMI; also known as third-person visual imagery) of strong muscle contractions on voluntary muscle strengthening. Eighteen young, healthy subjects were randomly assigned to one of three groups (6 in each group): internal motor imagery (IMI), external motor imagery (EMI), or a no-practice control (CTRL) group. Training lasted for 6 weeks (~15 min/day, 5 days/week). The participants' right arm elbow-flexion strength, muscle electrical activity, and movement-related cortical potential (MRCP) were evaluated before and after training. Only the IMI group showed significant strength gained (10.8%) while the EMI (4.8%) and CTRL (-3.3%) groups did not. Only the IMI group showed a significant elevation in MRCP on scalp locations over both the primary motor (M1) and supplementary motor cortices (EMI group over M1 only) and this increase was significantly greater than that of EMI and CTRL groups. These results suggest that training by IMI of forceful muscle contractions was effective in improving voluntary muscle strength without physical exercise. We suggest that the IMI training likely strengthened brain-to-muscle (BTM) command that may have improved motor unit recruitment and activation, and led to greater muscle output. Training by IMI of forceful muscle contractions may change the activity level of cortical motor control network, which may translate into greater descending command to the target muscle and increase its strength.

Objectives: To confirm the effect of occupational safety training and education programs (OSTEP) on needlestick injuries (NSIs) among nursing students in China., Methods: Compare the rates and the nature of NSIs before and after OSTEP among the nursing students in China. Firstly, questionnaires were delivered to 248 randomly selected nursing students from seven training hospitals to obtain basic information concerning relevant occupational NSIs. Then regular intervention measures through OSTEP on 246 nursing students had been introduced for four years. And the resultant information concerning relevant occupational NSIs was obtained afterwards. Finally, the data analysis was performed using SPSS software, version 11.5., Results: The rate of NSIs among these nursing students was relatively high before the OSTEP in China (average, 4.65 events/nurse). However, it decreased rapidly to 0.16 events/nurse average after the OSTEP. Occupational safety awareness and behavior in handling NSIs was improved in China. There was a significant difference in the results of Chi-square value (P<0.005)., Conclusions: NSIs are common in nursing students in China. The OSTEP can reduce NSIs and change practical behavior markedly among nursing students in China. We should perform OSTEP on nurse students before and during the clinical practice. We must also provide effective preventive measures to reduce this kind of problem in future., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To analyze the clinicopathologic characteristics of gastroenteropancreatic neuroendocrine neoplasm(GEP-NET) and explore the prognostic factors for patients with GEP-NET., Methods: Retrospectively reviews were conducted for the charts of 68 patients diagnosed pathologically with GEP-NET and treated at Sichuan Cancer Hospital during January 2001 to June 2012. The information of prognostic factors was retrieved and analyzed. Kaplan-Meier method was used to estimate survival rates and plot patient survival curves of patients at different levels of predictive factors. The association between clinicopathologic characteristic and prognosis in GEP-NET patients was assessed with Log-rank test. Meanwhile Cox proportional hazard model was used to select independent risk factors of patient survival., Results: Stomach (20/68,29.41%) and cardia (16/68,23.53%) were mostly involved. Frequent tumor sites for males were stomach and cardia (34/52,65.38%) while the most common site was intestinal canal for female (12/16) . Ages of disease onset were different significantly among patient groups of different sites (P = 0.023). The average age of intestinal NET was the highest while gastric NET had the lowest. During a median follow-up duration of 49 (3-120)months, there were 37 deaths (54.41%), including 30 from postoperative relapses. Postoperative survival time ranged from 4-115 months. The mean survival periods were (46 ± 7) months respectively. The 1, 3, and 5-year survival rates were 65.1%, 41.5% and 28.7% respectively. Univariate analyses showed that the risk factors of survival time were patient age over 60 years, tumor size > 2 cm, T2-4 stage of tumor, vascular invasion, lymph node metastasis, distant metastasis, positive surgical margin and pathological grades of neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC). Multivariate analysis indicated independent risk factors were tumor size > 2 cm and pathological grades of NEC and MANEC., Conclusions: GEP-NET may occur at multiple sites of digestive system and lack specific clinical manifestations. Tumor size, distant metastasis and pathological grades were independent prognostic factors for GEP-NET patients.

Our aim was to investigate cancer department nurses' attitudes and practices in response to pelvic radiation patients' sexual issues in Sichuan, China. A self-made questionnaire survey was conducted with 150 registered nurses of six hospitals in China. Nurses were asked about their experiences regarding consultation about sexual issues and attitudes toward the sex-related statements of pelvic radiation patients. We analyzed the correlation factors for the attitudes about dealing with patients' sexual issues by using the χ(2)-test. Of the survey sample, 128 nurses (85.33%) responded. Of the respondents, 46.88% had been consulted about sexual issues by patients or families. In addition, 87.5% of the nurses believed that 'reliable information on sexual in pelvic radiotherapy is lacking', and 77.34% reported having 'an interest in undertaking education of knowledge about pelvic radiation patients' sexual issues'; yet only 4.69% had completed professional sexual education about pelvic radiation patients. The hospital type and bed number as well as nurse age and seniority also affected the responses. This study shows that discussing sexuality is still repressed in the patient-nurse relationship, and most nurses' in Chinese cancer departments lack knowledge about pelvic radiation patients' sexual problems.

Background: Gefitinib is widely used in patients with advanced non-small-cell lung cancer (NSCLC), in whom chemotherapy had failed. Previous trials reported inconsistent findings regarding the efficacy of gefitinib on overall survival (OS) and progression free survival (PFS). This study was to evaluate the effects of chemotherapy plus gefitinib versus chemotherapy alone on survival of patients with NSCLC., Methods: We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings for relevant literature. Randomized controlled trials (RCTs) comparing chemotherapy with and without gefitinib in the treatment of patients with advanced NSCLC were included in our analysis. The primary endpoints were OS and PFS., Results: Of 182 relevant studies, 12 were included in the final analysis, which consisted of 6844 patients with NSCLC. Overall, we noted that gefitinib therapy had an 8% improvement in the OS as compared to the gefitinib-free therapy, but this difference was not statistically significant (HR, 0.92; 95% CI: 0.85-1.00; P=0.051). Furthermore, gefitinib therapy had significantly longer PFS compared to gefitinib-free therapy (HR, 0.72; 95% CI 0.60-0.87, P=0.001). Patients receiving gefitinib therapy also had a more frequent objective response rate (ORR) than the control arm (OR, 2.51; 95% CI, 1.67-3.78, P < 0.001). Rashes, diarrhea, dry skin, pruritus, paronychia, and abnormal hepatic function were more frequent in the gefitinib therapy group., Conclusions: Treatment with gefitinib had a clear effect on PFS and ORR, and it might contribute considerably to the OS. Furthermore, there was some evidence of benefit for gefitinib therapy among patients with adenocarcinoma.

Aim: The net mechanical efficiency of wheelchair propulsion is very low, approximately 13%. It is necessary to look for effective practice methods to obtain greater output with less energy expenditure during wheelchair propulsions. Literature indicates that variable practice (VP) is more effective than constant practice (CP) in motor-skill learning. However, it is unknown if VP is more effective than CP in improving wheelchair propulsive efficiency. The purpose of the study was to determine how propulsive efficiency and propulsive timing were affected by variable practice and constant practice., Design: This was an observational and experimental study., Setting: The experiment was conducted in a well-controlled university research laboratory., Population: A total of 33 able-bodied subjects participated in this study., Methods: Participants were randomly placed into one of the three training groups, two constant practice groups and one variable practice group. One constant group practiced wheelchair propulsion on a roller system with a single speed, 30% of the maximum speed, while the other constant group practiced using 55% of the maximum speed. The variable group practiced with both speeds. Three dependent variables, propulsive efficiency, timing, and intercycle variability of the timing, were measured., Results: All groups improved the three dependent variables significantly after the training, and in general the VP group had greater improvement than the others in improving the propulsive efficiency., Conclusion: This study is the first to demonstrate the advantage of the VP over the CP in improving the propulsive efficiency., Clinical Rehabilitation Impact: This finding has great implication for paraplegics because they require greater workloads for upper-extremity activities.

Objective: We sought to investigate attitudes toward breast-conserving therapy (BCS) in early-stage breast cancer (EBC) patients from P. R. China and assess the factors influencing their decision., Background: There exists geographical difference in decision to perform mastectomy or BCS for EBC patients. To date, there has been no report on attitudes toward BCS or factors influencing the surgical choice in mainland China., Methods: A structured questionnaire was delivered to 1800 EBC patients. The questionnaire elicited information about general patients' characteristics, attitudes toward BCS, the roles of doctors and spouses, the levels of understanding of BCS, and the reasons for their preferences., Results: Of 1590 participants, only 7.3% anticipated BCS and this was significantly associated with patient age, income, occupation, martial status, education, levels of self-understanding of the disease, and doctors' and spouses' suggestions (P<0.05). Approximately 70% of doctors (71.0%) and 40% spouses (39.6%) advised patients not to conserve their breasts. Although the percentage of patients endorsing BCS was higher than that of those opposing it (43.7 vs 15.1%) and more patient believed BCS was beneficial for women (39.2%), even if given another opportunity, only 32.5% of patients preferred to choose it. Moreover, the level of understanding BCS among patients is low (well-known: less-known: never-heard, 2.3 vs 47.4 vs 13.3%)., Conclusions: These results suggested that Chinese EBC patients lack accurate and comprehensive understanding of BCS. More efforts are needed to educate breast cancer patients in mainland China toward BCS., (Copyright © 2011 John Wiley & Sons, Ltd.)

Background: It has been reported that antidiabetic drugs affect the risk of cancer and the prognosis of patients with diabetes, but few studies have demonstrated the influence of different antidiabetic agents on outcomes after anticancer therapy among patients with cancer. The objective of this study was to evaluate the influence of the antidiabetic drugs metformin and insulin on the prognosis of patients with advanced nonsmall cell lung cancer (NSCLC) plus type 2 diabetes who received first-line chemotherapy., Methods: Data on patients with NSCLC who had diabetes from 5 hospitals in China during January 2004 to March 2009 were reviewed retrospectively. Ninety-nine patients were included in the final analysis. The influence of metformin and insulin on chemotherapy response rates and survival in these patients was evaluated., Results: Chemotherapy with metformin (Group A) produced superior results compared with insulin (Group B) and compared with drugs other than metformin and insulin (Group C) in terms of both progression-free survival (PFS) (8.4 months vs 4.7 months vs 6.4 months, respectively; P = .002) and overall survival (OS) (20.0 months vs 13.1 months vs 13.0 months, respectively; P = .007). Although no significant differences in the response rate (RR) were observed between these 3 groups, when groups B and C (ie, the nonmetformin group) were combined, there was a tendency for better disease control in Group A than that in nonmetformin group. No significant difference in survival was observed between chemotherapy with insulin (Group B) versus other drugs (Group C)., Conclusions: The current data suggested that metformin may improve chemotherapy outcomes and survival for patients who have NSCLC with diabetes., (Copyright © 2011 American Cancer Society.)

Objective: To detect the changes of heat shock protein(HSP) expression in human hepatocellular carcinoma HepG2 cells after treated by quercetin through a proteomics strategy termed SILAC (stable isotope labeling by amino acids in cell culture)-MS (mass spectrometry)., Methods: HepG2 cells cultured in d3-labeled DMEM medium were passaged for more than ten generations to reach an enough high labeling ratio. MTT assay was used to assess the inhibitory effect of quercetin on proliferation of HepG2 cells. In SILAC, total protein was extracted from control HepG2 cells and those treated by 50 µmol/L quercetin for 48 h, and then mixed to a 1:1 ratio. After in-gel digestion and idenfication by LC-MS/MS analysis, quantification informations of changed proteins were acquired by searching on Mascot 2.0 program (MatrixScience Ltd., London) against SWISS-PROT protein database. To ensure a high confidence level for identification, those peptides with Mascot scores below the threshold value were excluded from analysis and not included in the list of quantified proteins (P < 0.01). Protein abundance was calculated as ratios of the peak intensity of the fragment ions from the labeled versus the unlabeled peptides. RT-PCR was uesd to verify the reliability of HSPs changes by quercetin treatment from the SILAC-MS results., Results: After passaged for ten generations, the d3-labeling ratio was above 95%. MTT showed that quercetin inhibited the proliferation of HepG2 cells obviously, with a IC(50) close to 50 µmol/L, and in a dose-dependent and time-dependent manner. The MS showed that the expression of almost all heat shock family proteins was down-regulated a lot. The expression of HSP90 exposed to quercetin for 48 h was decreased to 49.3% of the normal HepG2 cells, and the expression of HSP70 was decreased to 43.6% of the normal Hep G2 cells. Quantitation information showed that the expression of HSP90α, HSP76, HSP60 and HSP27 was declined to 59.3%, 44.2%, 51.3% and 62.6%, respectively. Those results demonstrated that the quantification for changed protiens by SILAC-MS was correct., Conclusions: Quercetin can exert a significant inhibitory effect on whole expression of heat shock proteins in HepG2 cells. We suppose this maybe one of the pathways through which quercetin plays an important anti-tumor role. SILAC-MS is a reliale technique and can be used to quantify the changes of whole protein spectrum in HepG2 cells before and after treatment with some exogeneous factors.

Objective: To explore the feasibility of using enriched bone marrow (BM) compound with fibrin glue (FG) in repairing old radial bone defect., Methods: Totally 36 New Zealand rabbits were equally randomized into three groups: simple FG group, BM+FG group, and enriched BM+FG group. A 1.5-cm segmental bone defect was made at the left radial in each animal. After one month, the defect was implanted with the engineered bone. Before implantation, a compound of enriched BM with FG underwent electron microscopy, long-term culture, and bacteriological culture. Four, 8, and 12 weeks after operations, the osteogenetic effect was evaluated using X-ray observation, HE staining, or Van Gieson staining, and a semi-quantitative analysis was performed., Results: Electron microscopy showed enriched BM were compatible well with FG. No bacterial contamination or oncogenicity was observed after long-term culture. X-ray showed the repair effectiveness was significantly higher in BM+FG group and enriched BM+FG group than in simple FG group. Eight and 12 weeks after surgery, the Yang scores were significantly higher in enriched BM+FG group than in BM+FG group [(9.348±0.364évs.(7.984±0.229éìF=40.167ìP=0.001; (12.664±0.388)vs. (10.584±0.836é, F=20.3647ìP=0.004]. In addition, the Yang's scores at bone defects in BM+FG group and enriched BM+FG group were higher at the 12(th) week than in the 8(th) week. (F=36.004ìP=0.001; F=155.141ìP=0.000; respectively)The bone defects were repaired at varied degrees were histologically observed in BM+FG group and enriched BM+FG group during the observations., Conclusion: Implantation of BM+FG or enriched BM+FG are effective in repairing old radial bone defects, while simple FG shows not such effect.

Objective: To investigate the preparation method of polystyrene core-poly (acrylamide-acrylic acid) shell fluorescent microspheres., Methods: The polystyrene core-poly (acrylamide-acrylic acid) shell (P-(St-co-AAM)) fluorescent microspheres were prepared using fluorescent microspheres as the core and acrylamide/acrylic as polymerization monomer. Reaction conditions affecting the morphology of core-shell structure including feeding mode, initiator, cross linker, pH, concentration and swelling were studied., Result: Fluorescent microscopy showed that the relatively uniform particle sizes were distributed in a range of 7-8 μm. Fourier transform infra-red spectroscopy (FT-IR) proved the existence of poly (acrylamide-acrylic acid) shell and amide group on the surface. The optimal conditions for seeding polymerization: azobisisobutyronitrile was used as the initiator in the absence of cross linker, after a 40 h swelling treatment by using alcohol with the appropriate reaction temperature (70 degree), reaction time (3 h) and pH(6-7). The average dispersion and stability were 25.14 % and 90.21%, respectively. The fluorescein release percentage was kept stable at approximately 30% after 40 h., Conclusion: The fluorescent microspheres prepared by this method have core-shell structure and satisfactory fluorescence properties with good dispersion and stability.

Objectives: To describe and characterize the rates and the nature of needlestick injuries among nursing students in China., Methods: A questionnaire was delivered to 248 randomly selected nursing students from seven training hospitals to obtain information relevant occupational needlestick injuries., Results: A total of 1144 incidents of needlestick injuries were reported among the 246 nurses during the time period of internship. The overall rate of needlestick injuries among these nurses was 100%, according to this survey. Insufficient awareness of occupational safety and limited work experience with handling needlestick injuries in these nurse students were significantly reported. In addition, when stratified by departments, the highest rate of needlestick injuries was seen in the surgery department. The occurrence of needlestick injuries is significantly related to clinical practice behaviors., Conclusions: Needlestick injuries are commonly reported in nursing students in China. Enhanced awareness of occupational safety in nursing students is expected to reduce the risk of needlestick injuries., (Copyright 2009 Elsevier Ltd. All rights reserved.)