Real-world evidence of osimertinib in Chinese patients with EGFR T790M-positive non-small cell lung cancer: a subgroup analysis from ASTRIS study.

PURPOSE: ASTRIS study aimed the largest to evaluate the effectiveness and safety of second- or higher-line osimertinib in patients with advanced/metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC) in the real-world setting. Here we report the results of Chinese patients in ASTRIS study. METHODS: Adults with EGFR T790M-positive advanced NSCLC pretreated with EGFR-tyrosine kinase inhibitor (EGFR-TKI), having a WHO performance status score of 0-2 and asymptomatic, stable central nervous system (CNS) metastases were included. All patients received once-daily osimertinib 80 mg orally. The outcomes included investigator-assessed clinical response, progression-free survival (PFS), time-to-treatment discontinuation (TTD), and safety. RESULTS: A total of 1350 patients were included. Response rate was 55.7% (95% confidence interval [CI] 0.53-0.58). The median PFS and the median TTD were 11.7 months (95% CI 11.1-12.5) and 13.9 months (95% CI 13.1-15.2), respectively. Overall, 389 patients (28.8%) had at least one protocol-specified adverse event (AE); AEs of interstitial lung diseases/pneumonitis-like events and QT prolongation were reported in 3 (0.2%) and 59 (4.4%) patients, respectively. CONCLUSION: Osimertinib was effective in Chinese patients with T790M-positive NSCLC who had progressed after first- or second-generation EGFR-TKI in real-word setting and the results were consistent with ASTRIS study overall population and AURA studies. No new safety signals or events were identified. CLINICAL TRIAL NUMBER: NCT02474355.

A phase III randomized, double-blind, placebo-controlled trial of the denosumab biosimilar QL1206 in postmenopausal Chinese women with osteoporosis and high fracture risk.

The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.

The mediator role of stigma in the association of mindfulness and social engagement among breast cancer survivors in China.

PURPOSE: This study aims to explore the association between mindfulness and social engagement among Chinese breast cancer survivors (BCSs) and the mediator role of stigma in the relation of mindfulness and social engagement. METHODS: This cross-sectional study was conducted among 937 BCSs from March to April 2021 in Shanghai, China. Data were collected using the Mindful Attention Awareness Scale, the Stigma Scale for Chronic Illness 8-item version, and the index of social engagement. Descriptive statistics, independent-sample t-test, one-way ANOVA, and regression analyses were used to explore the role of stigma in the association of mindfulness and social engagement among Chinese BCSs. RESULTS: Social engagement levels differed significantly by participant's BMI, education level, employment status, personal monthly income, monthly per capita household income. Mindfulness was positively correlated with social engagement, and stigma was negatively correlated with mindfulness and social engagement among Chinese BCSs. Stigma plays a complete mediating role in the relationship between mindfulness and social engagement in BCSs. CONCLUSION: In the practice of individual mindfulness intervention on social engagement of BCSs, health care providers should identify and eliminate the constraints, which restrain the reduction of stigma level while individual mindfulness is being enhanced.

[Efficacy and adverse effects of Ningmitai Capsules combined with antibiotics in the treatment of chronic prostatitis: A meta-analysis].

OBJECTIVE: To study the effect, treatment course and adverse reactions of Ningmitai Capsules (NMT) in the treatment of chronic prostatitis (CP). METHODS: We searched the CNKI, Wanfang, COMDD and VIP databases, Cochrane Library, PubMed, EMBASE and Chinese academic conference papers for related articles before October 2019 on the treatment of CP with NMT, evaluated the quality of the literature with the Jadad Scale, and conducted a meta-analysis using the Stata14 software. RESULTS: Totally, 20 articles were included in this study, involving 3558 cases of CP, 1807 in the observation group and 1751 as controls. In the treatment of CP, NMT combined with quinolone, tetracycline or macrolide exhibited remarkably better effect than any of the above antibiotics used alone (RR ［95% CI］: 1.270 ［1.215－1.328］, 1.232 ［1.132－1.340］ and 1.239 ［1.130－1.359］, respectively) and the combination therapy also showed a higher total efficacy after 2, 4 and 8 weeks of medication (RR ［95% CI］: 1.256 ［1.185－1.330］, 1.245 ［1.165－1.330］ and 1.244 ［1.131－1.369］, respectively), though a little lower at 4 and 8 than at 2 weeks. There was no statistically significant difference in the incidence rate of adverse reactions between the NMT combination and antibiotics alone groups (P = 0.441). CONCLUSIONS: NMT combined with antibiotics, particularly with quinolone, is superior to antibiotics alone in the treatment of CP, though with no statistically significant difference in the incidence rate of adverse reactions between the two options. The length of medication does not inference the therapeutic effect.

Association between circulating CD39+CD8+ T cells pre-chemoradiotherapy and prognosis in patients with nasopharyngeal carcinoma.

BACKGROUND: The mortality rate among patients with nasopharyngeal carcinoma (NPC) has improved significantly with the advent of chemoradiotherapy strategies. However, distant metastasis remains problematic. Tumor-specific reactivity in cancer patients has been detected exclusively in CD39+ T cells, particularly in CD39+CD103+ T cells. Circulating cancer-specific T cells are important for protecting against metastasis. This study aimed to evaluate the predictive value of circulating CD39+CD8+ T cells for metastasis in patients with NPC. METHODS: We performed a cross-sectional, longitudinal study of 55 patients with newly diagnosed NPC of stage III-IVa. All patients were initially treated with standard combined chemoradiotherapy. Blood samples were obtained from 24 patients before and at 1 month and 6 months after treatment. T cell expression of CD39 and CD103, together with the markers of T cell exhaustion programmed death-1 (PD-1)/T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and markers of cell differentiation CD27/CC-chemokine receptor 7/CD45RA, was examined by flow cytometry. The Wilcoxon rank-sum test analysis was used to analyze the differences between two groups. Kaplan-Meier analysis was used for analysis of progression-free survival (PFS). RESULTS: The expression of circulating CD39+CD8+ and CD39+CD103+ CD8+ T cells was significantly higher in patients without distant metastasis (CD39+CD8+: 6.52% [1.24%, 12.58%] vs. 2.41% [0.58%, 5.31%], Z=-2.073, P=0.038 and CD39+CD103+CD8+: 0.72% [0.26%, 2.05%] vs. 0.26% [0.12%, 0.64%], Z=-2.313, P = 0.021). Most CD39+ T cells did not express PD-1 or Tim-3. Patients with high expression of CD39+CD103+CD8+ T cells had better PFS than patients with low expression (log rank value = 4.854, P = 0.028). CD39+CD8+ T cells were significantly elevated at 1-month post-treatment (10.02% [0.98%, 17.42%] vs. 5.91% [0.61%, 10.23%], Z = -2.943, P = 0.003). The percentage of advanced differentiated CD8+ T cells also increased at 1-month post-treatment compared with pre-treatment (33.10% [21.60%, 43.05%] vs. 21.00% [11.65%, 43.00%], Z = -2.155, P = 0.031). There was a significant correlation between elevated CD39+CD8+ T cells and increased effector memory T cells (intermediate stage: r = 0.469, P = 0.031; advanced stage: r = 0.508, P = 0.019). CONCLUSIONS: CD39+CD8+ circulating T cells have preserved effector function, contributing to an improved prognosis and a reduced risk of metastasis among NPC patients. These cells may thus be a useful predictive marker for a better prognosis in patients with NPC.

The relationship between expression of PD-L1 and HIF-1α in glioma cells under hypoxia.

Hypoxia inducible factor-1α (HIF-1α) up-regulates the expression of programmed death ligand-1 (PD-L1) in some extracranial malignancies. However, whether it could increase PD-L1 expression in intracranial tumor is still unknown. Here, we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. In glioma patients, HIF-1α and PD-L1 were overexpressed in high grade glioma tissues and were significantly associated with poor survival. In glioma cells, PD-L1 expression was induced under hypoxia condition, and the enhanced PD-L1 expression was abrogated by either HIF-1α knock-down or HIF-1α inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1α to PD-L1 proximal promoter region, providing evidence that HIF-1α up-regulates PD-L1 in glioma. In glioma murine model, the combination treatment with HIF-1α inhibitor and anti-PD-L1 antibody caused a more pronounced suppressive effect on tumor growth compared to either monotherapy. Immunologically, the combination treatment improved both dendritic cell (DC) and CD8+ T cell activation. Overall, our results demonstrated that positive correlation between PD-L1 and HIF-1α in glioma, and provide an alternative strategy, inhibiting HIF-1α, as combination therapies with immunotherapies to advance glioma treatment.

Stress, coping strategies and expectations among breast cancer survivors in China: a qualitative study.

BACKGROUND: Breast cancer is a common tumor in China and has become a public health problem in modern society. Stress plays an important role in the occurrence and progression of cancer. At present, the current situation of stress on breast cancer survivors (BCSs) in China has not been fully understood. This study aims to explore the stress and coping strategies of Chinese BCSs, which provide suggestions to help BCSs reduce stress. METHODS: Sixty-three BCSs from the Shanghai Cancer Rehabilitation Club in China were included in this study and were divided into eight focus groups. These were transcribed verbatim, coded using thematic analysis and analyzed using NVivo 11. RESULTS: Three themes were extracted from the data to address our research objectives: stress, coping strategies and expectations. The stress of BCSs included psychological stress, stress caused by physical pain, economic stress, stress caused by the change of life status, and stress caused by information overload; the coping strategies included self-strategies and help from others; from the perspective of the survivors, they put forward their expectations for both the society and themselves. CONCLUSIONS: This study shows that BCSs face a variety of stress. In the face of stress, BCSs need comprehensive support, including social and family support to cope with stressors. The findings from this study provide evidence for improving the quality of life among BCSs.

The Change of Soluble Programmed Cell Death-Ligand 1 in Glioma Patients Receiving Radiotherapy and Its Impact on Clinical Outcomes.

Background: The programmed cell death ligand 1 (PD-L1) plays a key role in glioma development. However, due to the specificity of glioma's anatomical position, the role of its expression as a tumor biomarker is limited. It has been proven that the levels of soluble programmed death-ligand 1 (sPD-L1) are associated with prognosis in many malignancies including glioma. However, the expression of sPD-L1 in glioma patients receiving radiotherapy (RT) remains unclear. The purpose of this study was to evaluate the concentration of sPD-L1 in the plasma of glioma patients before and after RT and to explore its relationship with clinical outcomes. Methods: Between October 2017 and September 2018, glioma patients treated with RT (30 ± 10 Gy, 2 Gy/f) were enrolled, and blood samples were collected before and after RT. We quantified the sPD-L1 levels by enzyme-linked immunosorbent assay (ELISA). The isocitrate dehydrogenase-1 (IDH-1) mutational status and Ki-67 expression of tumors were evaluated by immunohistochemistry. Glioma murine model were used to address whether circulating sPD-L1 molecules are directly targeted by an anti-PD-L1 antibody. The associations between sPD-L1 and clinical features were assessed with Pearson's or Spearman's correlation analysis. The progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan-Meier method. Results: Sixty glioma patients were included, with a median age of 52 years. The proportions of grade I, II, III, and IV gliomas were 6.7%, 23.3%, 28.4%, and 41.6%, respectively. The baseline sPD-L1 levels were significantly associated with tumor grade, IDH-1 mutation status and Ki-67 expression. Using 14.35 pg/ml as the cutoff, significantly worse PFS and OS were both observed in patients with higher baseline levels of sPD-L1 (P = 0.027 and 0.008, respectively). RT significantly increased the mean level of sPD-L1 (P < 0.001). Further analysis showed that the level of sPD-L1 in IDH-1 mutation patients was higher than that in wild-type patients. Furthermore, an analysis of glioma murine model indicated that anti-PD-L1 antibody combine with RT can be a potentially powerful cancer therapy. Conclusion: This study reported that sPD-L1 might be a potential biomarker to predict the outcome in glioma patients receiving RT. The elevated level of sPD-L1 after RT suggested that the strategy of a combination of immune checkpoint inhibitors and RT might be promising for glioma patients, especially for those with IDH-1 mutations.

Effects of physical activity and stress on the relationship between social capital and quality of life among breast cancer survivors.

This study aims to investigate the serial multiple mediation of physical activity and perceived stress in the relationship between individual social capital and quality of life (QOL) in breast cancer survivors (BCSs). This study was conducted among 520 BCSs between March and April 2017 in Shanghai, China. Data were collected using the Individual Social Capital Scale, the Health-Promoting Lifestyle Profile-II, the Perceived Stress Scale-14 and the EORTC QLQ-C30. Ordinary least-squares regression and the bootstrap method was used to test the significance of the serial multiple mediation model. The serial-multiple mediations of physical activity and perceived stress were found significant in the relationship of QOL with all five dimensions of individual social capital. The separate mediations of two single mediating variables were found significant in the relationship of QOL with control over life and feeling about the community. In the relationship of QOL with social participation, social network and social support, the separate mediation of physical activity was significant, while the separate mediation of perceived stress was not significant. A multidisciplinary team approach and a variety of delivery systems are needed to address the social, physical and psychological issues for improving QOL among BCSs.

Novel Albumin Nanoparticle Enhanced the Anti-Insulin-Resistant-Hepatoma Activity of Metformin.

INTRODUCTION: Metformin is an ideal candidate to treat the liver tumor with insulin resistance because of its good performance in the treatment of type 2 diabetes and the advantage in cancer therapy. We aim to develop a delivery system with higher efficiency than free drug. METHODS: Metformin-bovine serum albumin (met-BSA) nanoparticles (NPs) were prepared using the anti-solvent precipitation method with a stabilizer of BSA for particle growth. The therapeutic effect of the drug was tested by the insulin-resistant HepG2 cells and C57BL/6J mice at a glucose starvation condition. The interaction mechanism of the drug and the protein during the formation of the NPs was tested using a series of spectroscopy. RESULTS: Metformin and BSA formed nonporous and spherical particles of about 200 nm with proper lognormal distribution and thermostability. The cellular uptake, as well as the anti-liver cancer activities of met-BSA, was enhanced dramatically compared with the free drug. The thermodynamic studies suggested that the weak binding of metformin to BSA was governed by hydrogen bonds and van der Waals forces. Moreover, the results of synchronous, circular dichroism (CD) and three-dimensional fluorescence demonstrated that the BSA skeleton and chromophore microenvironments were changed in the presence of metformin. CONCLUSION: Therefore, met-BSA has been proved as a simple yet effective therapeutic agent for cancer with insulin resistance, promising for future clinic translations in cancer treatment.

In vitro and in vivo evaluation of the safety and efficacy of a novel liquid fiducial marker for image-guided radiotherapy.

The true extent of a tumor is difficult to visualize, during radiotherapy, using current modalities. In the present study, the safety and feasibility of a mixture of N-butyl cyanoacrylate and lipiodol (NBCA/Lip) was evaluated in order to investigate the optimal combination for application as a fiducial marker for radiotherapy. Four combinations of NBCA/Lip injection (1:1-0.1, 1:1-0.15, 1:3-0.1 and 1:3-0.15 ml) were injected into the subcutaneous tissue of BALB/c mice. The changes in gross histopathology, body weight, skin score, marker volume, neutrophil and macrophage counts were observed to analyze the effects of the different mixing ratios and injection volumes, in order to identify the best combination. Evaluation according to the International Organization for Standardization criteria was further conducted in order to test the biocompatibility of the mixture, including an acute systematic assay with mice, cytotoxicity with L929 fibroblasts and delayed-type hypersensitivity tests with guinea pigs and an intradermal test with rabbits. The results revealed that at the seventh week, 42 markers (42/48; 87.5%) were still visible using computed tomography (CT) imaging. No serious adverse effects were observed throughout the study period; however, the combination of 1:1-0.1 ml had the lowest body weight and worst skin score. A review of the histopathological reaction to NBCA/Lip revealed a combination of acute inflammation, chronic inflammation, granulation tissue, foreign-body reaction and fibrous capsule formation. The 1:1 NBCA combination ratio resulted in the most intense tissue repair reaction and a slower degradation rate of markers. In general, the combination of 1:3-0.15 ml had a better fusion with local tissue, maintained a stable imaging nodule on CT images for 7 weeks and the final biocompatibility test demonstrated its safety. Overall, the findings of the present study demonstrated NBCA/Lip as a safe and feasible fiducial marker, when using the 1:3-0.15 ml combination.

Combination therapy: Meta-analysis of the effects of TACE and cryoablation on hepatocellular carcinoma.

BACKGROUND: This study systematically reviews the data for transcatheter arterial chemoembolization (TACE) alone or combined TACE and cryoablation therapy of hepatocellular carcinoma, aiming to provide clinical choice references for treatment of cancer. METHODS: Electronic databases (PubMed, EMBASE, China National Knowledge Infrastructure, and Google Scholar) were systematically searched to include relevant studies published in English and Chinese between Jan 1, 2000, to July 31, 2017. The analysis was conducted in RevMan 5.3 based on random effects models. RESULTS: Nineteen trials (n = 1427) were included. Combined TACE and cryoablation therapy had higher survival rate (1-year survival [RR 1.37; 95%-CI 1.26,1.49], 2-year survival [RR 1.50; 95%-CI 1.25,1.79], 3-year survival [RR 1.67; 95%-CI 1.16,2.40]), complete necrosis [RR 2.53; 95%-CI 2.07,3.10] and tumor control [RR 1.57; 95%-CI 1.40,1.75], which is more favorable for long-term efficacy of non-surgical hepatocellular carcinoma. Tumor recurrence of control group was above combination therapy [RR 0.27; 95%-CI 0.17, 0.43]. Compared with transcatheter arterial chemoembolization, effect of combination therapy occurred mainly in the survival, complete necrosis, tumor control, and recurrence. Taking combination therapy was generally more effective than taking TACE only. CONCLUSION: Compared with TACE only used to treat cancer, combination therapy had the best effect profile in general, and it had better survival in HCC when taking an integrated approach. The prognosis of treatments based on combination therapy is modulated by cryoablation.

The impact of social capital on physical activity and nutrition in China: the mediating effect of health literacy.

BACKGROUND: Physical activity and good nutrition are important behavioral factors in promoting health and preventing disease. It is important to understand the factors affecting physical activity and nutrition. The purpose of this study was to explore whether social capital has an effect on physical activity and nutrition, and whether health literacy plays a mediating role between social capital and physical activity as well as nutrition. METHODS: This cross-sectional study was performed in a certain district of Shanghai in March and April 2017. Data was collected using a self-reported questionnaire, which included questions on sociodemographic characteristics, social capital, health literacy and health-promoting lifestyle profile-II. Health-promoting lifestyle profile-II measures the behaviours or habits of physical activity and healthy nutrition. An explore factor analysis of the principal components with varimax rotation was carried out on the social capital scale. Descriptive statistics was used to summarize the sociodemographic of participants. Mediation analysis was performed using the bootstrapping tests to examine whether health literacy mediate the relationship between social capital and physical activity as well as nutrition. RESULTS: The explore factor analysis results showed that social capital has five dimensions, namely social participation, social support, social network, control over life and feelings about the community. There is a positive correlation between social capital, health literacy, physical activity and nutrition. The correlation coefficient varied from 0.135 to 0.594. Mediation analysis demonstrated health literacy played a partial mediating effect between social capital and physical activity as well as nutrition. In the relationship between physical activity and social capital, the indirect effect of health literacy accounted for 8.20 to 12.65% of the total effect. In the relationship between nutrition and social capital, the mediation effect of health literacy accounted for 4.93 to 12.71% of the total effect. CONCLUSION: Social capital can promote physical activity and nutrition by disseminating health information. Enhancing the social capital of residents will help increase physical activity and develop healthy eating habits. Attention should also be paid to the improvement of residents' health literacy.

Ten-Year Outcomes Of Intensity-Modulated Radiotherapy (IMRT) Combine With Chemotherapy Versus IMRT Alone For Stage II Nasopharyngeal Carcinoma In The Real-World Study (RWD).

OBJECTIVES: The aim was to define the role of chemotherapy in stage II nasopharyngeal carcinoma (NPC) and to identify the toxicity of chemotherapy for these patients in the era of intensity-modulated radiotherapy (IMRT). METHODS: Between January 2002 and December 2013, 169 patients with stage II NPC were analyzed. Of these patients, 149 patients treated with chemotherapy were divided into three groups as follows: neoadjuvant chemotherapy followed by IMRT (NCT) group, concurrent chemotherapy with IMRT (CCRT) group, and neoadjuvant chemotherapy followed by CCRT (NC+CCRT) group. In addition, 20 patients received IMRT alone. We retrospectively assessed the 10-year survival and acute adverse effects in the patients using SPSS software. RESULTS: The median follow-up time was 93 months (2-160 months). The 10-year OS of the NCT, CCRT, NC+CCRT groups vs the IMRT alone group was 69.8%, 63.4%, 69.7% vs 72.4%, respectively (P=0.664, 0.940, and 0.998, respectively). Both univariable and multivariable analyses showed that the addition of chemotherapy to IMRT did not significantly improve the 10-year survival outcomes. The hematotoxicity and mucous reaction of patients with chemotherapy were more serious than those with IMRT alone (P=0.007 and 0.049). Distant metastasis for stage II NPC patients mostly occurred within 3 years, which is very different from patients with advanced NPC. CONCLUSION: Patients with stage II NPC who are treated with IMRT may obtain satisfactory long-term survival outcomes. The additional chemotherapy cannot significantly increase survival; however, it may remarkably increase treatment-associated acute toxic reactions.

Potential of Gd-EOB-DTPA as an imaging biomarker for liver injury estimation after radiation therapy.

BACKGROUND: Hepatic radiation injury severely restricts irradiation treatment for liver carcinoma. The purpose of this study was to investigate the clinical application of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI (EOB-MRI) in the assessment of liver function after external radiation therapy and to determine the relationship between focal liver reaction (FLR) and liver function. METHODS: A total of 47 patients with liver malignancies who underwent external beam radiation therapy were enrolled. EOB-MRI was performed on each patient at approximately one month post-radiotherapy. The hepatobiliary (HPB) phase images from EOB-MRI were fused with the planning CT images, and the isodose lines from the patients' treatment plans were overlaid onto the fused images. The correlation of the EOB-MR image intensity distribution with the isodose lines was studied. We also compared liver function in patients between pre-treatment and post-treatment. RESULTS: Decreased uptake of Gd-EOB-DTPA, which was manifested by well-demarcated focal hypointensity of the liver parenchyma or FLR to high-dose radiation, was observed in the irradiated areas of 38 patients. The radiotherapy isodose line of decreased uptake area of Gd-EOB-DTPA was 30-46 Gy. The median corresponding dose curve of FLR was 34.4 Gy. Nine patients showed the absence of decreased uptake area of Gd-EOB-DTPA in the irradiated areas. Compared to the 38 patients with the presence of decreased uptake area of Gd-EOB-DTPA, 9 patients with the absence of decreased uptake area of Gd-EOB-DTPA showed significant higher levels of total bile acid, total bilirubin, direct bilirubin and alpha-fetoprotein (P < 0.05). There were no significant differences in alanine transaminase, aspartate aminotransferase, gamma-glutamyl transpeptidase or albumin levels between the two groups (P > 0.05). CONCLUSIONS: Visible uptake of Gd-EOB-DTPA by the liver parenchyma was significantly associated with liver function parameters. EOB-MRI can be a valuable imaging biomarker for the assessment of liver parenchyma function outside of radiation area.

[The effect of fluoride varnish Duraphat in preventing deciduous dental caries in preschool children].

PURPOSE: To evaluate the effect of fluoride varnish Duraphat on preventing caries of primary teeth caries, and provide scientific basis for the establishment of oral health care. METHODS: 1140 preschool children aged 3~4 years old were chosen from 25 public kindergartens in Xuhui district of Shanghai by cluster sampling method, they were divided into 2 groups on a voluntary basis with the informed consent of the child's parents. 762 preschool children in Fluoride Varnish group were taken oral examination and used fluoride varnishes every 6 months, 378 preschool children in the control group were without treatment. Oral health instruction was given to all the children. The data of caries prevalence, mean dmft, caries incidence and mean increments of dmft (decayed, missing and filled teeth) of 2 groups were compared. The results were analyzed using SAS 9.4 software package. RESULTS: After 2 years, caries prevalence, mean dmft, caries incidence and mean increments of dmft of fluoride varnish groups were lower than those of control group and the difference was statistically significant (P＜0.05). CONCLUSIONS: Fluoride varnish Duraphat is effective in decreasing caries incidence and mean dmft increments of primary teeth in preschool children and is worthy to be used widely in Xuhui district.

Axillary management still needed for patients with sentinel node micrometastases.

More attention has been paid to the axillary management over the past 50 years, and clinical practice has been changed as results of the random controlled trials. The American College of Surgeons Oncology Group Z0011 and International Breast Cancer Study Group (IBCSG) 23-01 trials provided high-level evidence to support the omission of axillary lymph nodes dissection (ALND) in sentinel lymph node (SLN)-positive patients receiving breast-conserving surgery (BCS) and adjuvant systemic treatment. In patients treated with BCS, whole breast irradiation (WBI) with tangential fields could lead to substantial axillary irradiation and control the residual tumor burden in axilla, whereas (intraoperative) partial breast irradiation has no therapeutic effect on these residual axillary metastases. In the observation group of the IBCSG 23-01 trial, 425 patients received BCS and 80 (18.8%) of them just underwent intra-operative radiotherapy. While the 10-year axillary recurrence rate was acceptable low (1.7%, 8/467) in the no ALND group, it was 4.5% (6/134) in patients without axillary management, which was significantly higher than that of 0.6% (2/333) in patients with axillary management (P=0.0024). Should we accept an axillary recurrence rate as high as 4.5% in patients with only SLNs micrometastases? What is the best way to control the residual tumor burden in the axilla and decrease the recurrence rate if there is no ALND? The evidence showed that both WBI after BCS (Z0011, AATRM [Agència d'Avaluació de Tecnologia i Recerca Mèdiques]) and axillary regional nodal irradiation after mastectomy/BCS OTOASOR (Optimal Treatment Of the Axilla - Surgery Or Radiotherapy), AMAROS (After Mapping of the Axilla: Radiotherapy Or Surgery) could control the regional residual tumor burden when the SLN is positive and an ALND is omitted. In the modern era, systemic therapy could further decrease the risk of local/regional recurrences. After the subanalysis of the POSNOC (POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy), SERC (Sentinelle Envahiet Randomisation du Curage), and Dutch BOOG (BOrstkanker Onderzoek Groep) trials, a prediction model might be established to identify those patients who could beneft from no axillary management as a guide to clinical practice. At present, axillary management should still be required for patients with SLN micrometastases.

HMGB1 correlates with angiogenesis and poor prognosis of perihilar cholangiocarcinoma via elevating VEGFR2 of vessel endothelium.

Perihilar cholangiocarcinoma (PHCCA) is the most common type of cholangiocarcinoma with low resection rate and high morbidity. The study of PHCCA biomarkers made progresses slowly compared with intrahepatic cholangiocarcinoma because of surgical complexity and low possibility of radical surgery, which resulted in the difficulty of specimen obtainment. To screen and identify new biomarkers in PHCCA, we constructed a retrospective cohort with 121 PHCCA patients and a prospective cohort consisting of 64 PHCCA patients, and screened the candidate biomarkers by immunohistochemistry and quantified PCR. In our study, expression of high mobility group box 1 (HMGB1) was demonstrated to be significantly associated with microvascular density (MVD) and unfavorable prognosis of PHCCA in both retrospective and prospective study. Moreover, HMGB1 concentrations in bile and serum of PHCCA patients and healthy controls were detected and compared. Postoperative serum HMGB1 and reflux cholangitis indicated recurrence and unfavorable prognosis of PHCCA. With experiments in vitro and in vivo, we demonstrated that intracellular HMGB1 could be released from PHCCA cells and induce invasion and angiogenesis with LPS stimulation. VEGFR2 expression in vessel endothelial cells was upregulated by the released HMGB1 from PHCCA, resulting in the ectopic angiogenesis. In conclusion, intracellular HMGB1 could be released from PHCCA cells and promote angiogenesis via elevating VEGFR2 in vessel endothelial cells. High expression of HMGB1 was associated with MVD and poor prognosis in clinical analyzation. Postoperative serum HMGB1 and cholangitis could predict high recurrence and unfavorable prognosis.

The Surgical Choice of Incidental Periampullary Carcinoma Management in Emergency Laparotomy.

BACKGROUND Laparotomy patients are occasionally diagnosed as having incidental periampullary cancers, making emergency pancreaticoduodenectomy (PD) inevitable. In this situation is difficult to decide whether to perform an emergency PD or a two-stage PD. MATERIAL AND METHODS A total of 27 patients who underwent emergency abdominal laparotomy were diagnosed with periampullary or pancreatic cancer during the operation without enough preoperative preparation. Ten patients underwent emergency one-stage PD and 17 patients underwent two-stage PD. Data of 137 patients with elective PD were selected as the control group. The preoperative, operative, and postoperative parameters, including hospital stay, medical cost, blood loss, and postoperative complications between elective PD and emergency PD (one-stage and two-stage) and between one-stage PD and two-stage PD were analyzed by chi-square test, Fisher test, or t test. RESULTS Patients undergoing emergency two-stage PD had less blood loss (P=0.014), while patients with one-stage PD had shorter hospital stay (P=0.004), shorter operation time (P=0.047), and lower treatment costs (P=0.003). Additionally, the complications rates between one-stage and two-stage PD had no significant difference (P=0.365). Elective PD was the optimal method due to shorter hospital stay (P<0.001), less hemorrhage (P<0.001), shorter operative time (P<0.001), and lower cost (P<0.001) compared with emergency PD. CONCLUSIONS Based on our experience, one-stage PD had advantages of shorter hospital stay, shorter operation time, and lower treatment costs, while two-stage PD had less blood loss. The emergency two-stage PD may be more suitable for patients with unstable vital signs if emergency PD is inevitable in an emergency laparotomy.

Sprouty2 suppresses progression and correlates to favourable prognosis of intrahepatic cholangiocarcinoma via antagonizing FGFR2 signalling.

Fibroblast growth factor receptor 2 (FGFR2) was demonstrated to correlate to the progression and prognosis of intrahepatic cholangiocarcinoma (ICC) by numerous evidences. However, as a well-recognized suppressor of FGFR2 signalling, the clinical significance of Sprouty (SPRY) family of ICC has not been investigated. In our study, the expressions of SPRY1-4 in 20 pairs of fresh tumour tissues were detected with qPCR, and in 108 cases of paraffin-embedded tissues with immunohistochemistry. The prognostic value of SPRY family in ICC was estimated with univariate analysis and multivariate analysis. As a result, SPRY2 was identified as an independent prognostic biomarker predicting favourable prognosis of ICC. High SPRY2 expression was correlated with good differentiation of ICC. With silencing SPRY2 expression, we demonstrated that SPRY2 could suppress FGFR2-induced ERK phosphorylation, migration, invasion and epithelial-mesenchymal transition (EMT) under FGF1 stimulation. By overexpressing SPRY2-wide type or SPRY2-Y55F, the tyrosine-55 of SPRY2 was demonstrated to be essential in suppressing ERK phosphorylation, tumour invasion and EMT of ICC cells. In conclusion, SPRY2 was correlated with favourable prognosis of ICC via suppressing FGFR2-induced ERK phosphorylation, invasion and EMT. The phosphorylation of SPRY2-Y55 was required in this tumour-suppressing function of SPRY2.