[Multicenter evaluation of minimal residual disease monitoring in early induction therapy for treatment of childhood acute lymphoblastic leukemia].

Objective: To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL). Methods: This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children's Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors. Results: Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×109/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively (χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant (χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively (χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%,χ2=4.13,P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%,χ2=4.06,P=0.044;(58.3±18.6)% vs. (85.7±3.2)%,χ2=9.44,P=0.002). Multivariate analysis showed that age (OR=0.58, 95%CI 0.35-0.97) and white blood cell count at first diagnosis (OR=0.43, 95%CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 (OR=0.55,95%CI 0.31-0.97), ETV6-RUNX1 fusion gene (OR=0.13,95%CI 0.03-0.54), MLL gene rearrangement (OR=2.55,95%CI 1.18-5.53) and white blood cell count at initial diagnosis (OR=0.52,95%CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions: The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

Wnt1 Promotes Cementum and Alveolar Bone Growth in a Time-Dependent Manner.

The WNT/ß-catenin signaling pathway plays a central role in the biology of the periodontium, yet the function of specific extracellular WNT ligands remains poorly understood. By using a Wnt1-inducible transgenic mouse model targeting Col1a1-expressing alveolar osteoblasts, odontoblasts, and cementoblasts, we demonstrate that the WNT ligand WNT1 is a strong promoter of cementum and alveolar bone formation in vivo. We induced Wnt1 expression for 1, 3, or 9 wk in Wnt1Tg mice and analyzed them at the age of 6 wk and 12 wk. Micro-computed tomography (CT) analyses of the mandibles revealed a 1.8-fold increased bone volume after 1 and 3 wk of Wnt1 expression and a 3-fold increased bone volume after 9 wk of Wnt1 expression compared to controls. In addition, the alveolar ridges were higher in Wnt1Tg mice as compared to controls. Nondecalcified histology demonstrated increased acellular cementum thickness and cellular cementum volume after 3 and 9 wk of Wnt1 expression. However, 9 wk of Wnt1 expression was also associated with periodontal breakdown and ectopic mineralization of the pulp. The composition of this ectopic matrix was comparable to those of cellular cementum as demonstrated by quantitative backscattered electron imaging and immunohistochemistry for noncollagenous proteins. Our analyses of 52-wk-old mice after 9 wk of Wnt1 expression revealed that Wnt1 expression affects mandibular bone and growing incisors but not molar teeth, indicating that Wnt1 influences only growing tissues. To further investigate the effect of Wnt1 on cementoblasts, we stably transfected the cementoblast cell line (OCCM-30) with a vector expressing Wnt1-HA and performed proliferation as well as differentiation experiments. These experiments demonstrated that Wnt1 promotes proliferation but not differentiation of cementoblasts. Taken together, our findings identify, for the first time, Wnt1 as a critical regulator of alveolar bone and cementum formation, as well as provide important insights for harnessing the WNT signal pathway in regenerative dentistry.

[Risk factors for surgical site infection after emergency abdominal surgery: a multicenter cross-sectional study in China].

Objective: Surgical site infection (SSI) is the most common infectious complication after emergency abdominal surgery (EAS). To a large extent, most SSI can be prevented, but there are few relevant studies in China. This study mainly investigated the current situation of SSI occurrence after EAS in China, and further explored risk factors for SSI occurrence. Methods: Multi-center cross-sectional study was conducted. Clinical data of patients undergoing EAS in 33 hospitals across China between May 1, 2019 and June 7, 2019 were prospectively collected, including perioperative data and microbial culture results from infected incisions. The primary outcome was the incidence of SSI after EAS, while the secondary outcomes were postoperative hospital stay, ICU occupancy rate, length of ICU stay, hospitalization cost, and mortality within postoperative 30 days. Univariate and multivariate logistic regression models were used to analyze the risk factors of SSI after EAS. Results: A total of 660 EAS patients aged (47.9±18.3) years were enrolled in this study, including 56.5% of males (373/660). Forty-nine (7.4%) patients developed postoperative SSI. The main pathogen of SSI was Escherichia coli [culture positive rate was 32.7% (16/49)]. As compared to patients without SSI, those with SSI were more likely to be older (median 56 years vs. 46 years, U=19 973.5, P<0.001), male [71.4% (35/49) vs. 56.1% (343/611), χ(2)=4.334, P=0.037] and diabetes [14.3% (7/49) vs. 5.1% (31/611), χ(2)=5.498, P=0.015]; with-lower preoperative hemoglobin (median: 122.0 g/L vs. 143.5 g/L, U=11 471.5, P=0.006) and albumin (median: 35.5 g/L vs. 40.8 g/L, U=9452.0, P<0.001), with higher blood glucose (median: 6.9 mmol/L vs. 6.0 mmol/L, U=17 754.5, P<0.001); with intestinal obstruction [32.7% (16/49) vs. 9.2% (56/611), χ(2)=25.749, P<0.001], with ASA score 3-4 [42.9% (21/49) vs. 13.9% (85/611), χ(2)=25.563, P<0.001] and with high surgical risk [49.0% (24/49) vs. 7.0% (43/611), χ(2)=105.301, P<0.001]. The main operative procedure resulting in SSI was laparotomy [81.6%(40/49) vs. 35.7%(218/611), χ(2)=40.232, P<0.001]. Patients with SSI experienced significantly longer operation time (median: 150 minutes vs. 75 minutes, U=25 183.5, P<0.001). In terms of clinical outcome, higher ICU occupancy rate [51.0% (25/49) vs. 19.5% (119/611), χ(2)=26.461, P<0.001], more hospitalization costs (median: 44 000 yuan vs. 15 000 yuan, U=24 660.0, P<0.001), longer postoperative hospital stay (median: 10 days vs. 5 days, U=23 100.0, P<0.001) and longer ICU occupancy time (median: 0 days vs. 0 days, U=19 541.5, P<0.001) were found in the SSI group. Multivariate logistic regression analysis showed that the elderly (OR=3.253, 95% CI: 1.178-8.985, P=0.023), colorectal surgery (OR=9.156, 95% CI: 3.655-22.937, P<0.001) and longer operation time (OR=15.912, 95% CI:6.858-36.916, P<0.001) were independent risk factors of SSI, while the laparoscopic surgery (OR=0.288, 95% CI: 0.119-0.694, P=0.006) was an independent protective factor for SSI. Conclusions: For patients undergoing EAS, attention should be paid to middle-aged and elderly patients and those of colorectal surgery. Laparoscopic surgery should be adopted when feasible and the operation time should be minimized, so as to reduce the incidence of SSI and to reduce the burden on patients and medical institutions.

Influence of miR-155 on behaviors of depression mice through regulating Wnt/ß-catenin signaling pathway.

OBJECTIVE: To study the influence of micro ribonucleic acid (miR)-155 on depression-like behaviors of depression mice, and to explore the role of Wnt/b-catenin signaling pathway in behavioral regulation of depression mice. MATERIALS AND METHODS: The mouse model of depression was established via chronic unpredictable mild stress (CUMS). All mice were randomly divided into control group (n=12), model group (n=12), and fluoxetine group (n=12). The expression level of miR-155 in the hippocampus of mice in each group was detected via quantitative Polymerase Chain Reaction (qPCR). The changes in the behaviors of mice in each group were evaluated via behavioral experiments. The apoptosis level in the hippocampus of mice in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Moreover, the content of inflammatory factors in the hippocampus of mice in each group was detected using the enzyme-linked immunosorbent assay (ELISA) kits. The expression levels of Wnt/b-catenin signaling pathway-related proteins in each group were detected via Western blotting. RESULTS: The expression level of miR-155 in the hippocampus was significantly higher in model group than that in control group (p<0.01). Meanwhile, the expression level of miR-155 was significantly lower in fluoxetine group than that in model group (p<0.01). There were no statistically significant differences in the crossing score and rearing score in the open field test among groups (p>0.05). Compared with those in control group, the immobility time in tail suspension test and forced swimming test were significantly increased (p<0.01), while the sucrose preference degree significantly declined (p<0.01) in model group. Fluoxetine could significantly reduce the immobility time in tail suspension test and forced swimming test (p<0.01) and increase the sucrose preference degree (p<0.01) in model group. The number of TUNEL-positive cells in the hippocampus of mice in model group was significantly larger than that in control group (p<0.01). Fluoxetine could effectively reduce the number of TUNEL-positive cells in the hippocampus (p<0.01). Compared with those in control group, the content of tumor necrosis factor-α (TNF-a), interleukin-1b (IL-1b), and IL-6 in the hippocampus was significantly increased (p<0.01), while the content of IL-10 was significantly decreased (p<0.01) in model group. Fluoxetine could effectively reduce the content of TNF-a, IL-1b, and IL-6 (p<0.01) and increase the content of IL-10 (p<0.01). Besides, in model group, the expression levels of dishevelled-1 (DVL-1) and b-catenin in hippocampus remarkably declined (p<0.01), while the expression levels of glycogen synthase kinase-3b (GSK-3b) and adenomatous polyposis coli (APC) were remarkably increased (p<0.01) compared with those in control group. Fluoxetine could effectively lower the expressions of GSK-3b and APC in the hippocampus (p<0.01) and increase the expressions of DVL-1 and b-catenin (p<0.01) in model group. CONCLUSIONS: MiR-155 is involved in regulating the depression-like behaviors of depression mice through promoting the release of inflammatory factors and the apoptosis of hippocampal neurons. Its mechanism may be related to the inhibition of the Wnt/b-catenin signaling pathway.

Specific computed tomography imaging characteristics of congenital mesoblastic nephroma and correlation with ultrasound and pathology.

INTRODUCTION: Congenital mesoblastic nephroma (CMN) is a common solid renal tumor in the neonate. Congenital mesoblastic nephroma can be divided into classic, cellular, and mixed types. The prognosis of CMN is very optimistic. But CMN can easily be misdiagnosed as the other malignant renal tumors by radiology. However, no studies have described the computed tomography (CT) imaging appearance of CNM in detail. The objective of this study is retrospective analyses of the multislice CT characteristics of CMN and their corresponding ultrasound findings and pathology. METHODS: This retrospective study reviewed the enhanced CT images of the CMNs and other renal tumors in children younger than 1 year in the past 10 years from the First Affiliated Hospital of Sun Yat-sen University. Two radiologists had noted the CT imaging characteristics of these images. t-test and Fisher's exact test were used in the comparison of imaging characteristics between the CMNs and other renal tumors. RESULTS AND DISCUSSION: Compared with other malignant renal tumors, the CMNs tend to appear as smaller round masses without clear coverage or clear boundary with the kidney in CT images (P < 0.01). The intratumor pelvis and the double-layer sign are the specific characteristics of CMNs (P < 0.01). The gender, quality of tumor (solid or solid-cystic), character of enhancement (homogeneous or heterogeneous enhancement), peri-renal hemorrhage, or peripheral lymph node enlargement showed no statistical significance (P > 0.05) between CMNs and other renal tumors. The appearances of CMN with classic components in the CT images are relevant to the pathological findings. The intratumor pelvis is caused by the classic components of CMN growing to encapsulate the pelvis. The double-layer sign in CT image correlates with the specific hypoechoic ring in ultrasound, which is caused by the slow blood flow and delay contrast agent filling in the blood sinus located in the peripheral part of the tumor. The differential diagnosis of CMN should include the other solitary renal tumors such as Wilms' tumor, clear-cell sarcoma of the kidney, and rhabdoid tumor of the kidney. CONCLUSION: The unclear coverage and unclear boundary with the kidney, the intratumor pelvis, and double-layer sign after contrast were specific CT imaging characteristics of CMN.

[Changing trends of topical anti-glaucoma medications in the Eye Hospital of Wenzhou Medical University during the past ten years].

Objective: To investigate the changing trends of topical anti-glaucoma medications in the outpatient of the Eye Hospital of Wenzhou Medical University over the decade 2005-2014. Methods: Retrospective case series study. The medications data of glaucoma outpatients in the Eye Hospital of Wenzhou Medical University were collected for the period of January 1(st) 2005 to December 31(st) 2014. SPSS 20.0 statistical software was used, mainly for statistical description of the data. The main outcome measures were the proportions of the prescriptions of different medications, and the proportions of the monotherapy and combination therapies. Results: During the 10 years, the number of glaucoma outpatients increased year by year, from 994 in 2005 to 3 266 in 2014, the gender ration was close to 1∶1, and the age were (57±18) years. The proportion of ß-blockers decreased from 56.7% (750/1 323) in 2005 to 33.1% (2 120/6 407) in 2014. The proportion of cholinergic agents decreased from 17.2% (227/1 323) in 2005 to 10.3% (663/6 407) in 2014. While the proportion of prostaglandins increased from 13.3% (176/1 323) in 2005 to 36.8% (1 916/5 209) in 2011, which was close to the 37.9% (1 972/5 209) of ß-blockers in 2011. In 2012, the prostaglandins proportion increased to 41.9% (2 435/5 810) exceeding the 37.2% (2 161/5 810) of ß-blockers, and became the most prescribed medication. The proportion of prostaglandins continued to increase to 46.9% (3 008/6 407) in 2014. The proportion of α(2)-agonists increased from 17.0% (225/1 323) in 2005 to 22.8% (1 460/6 407) in 2014. The proportion of carbonic anhydrase inhibitors increased from 9.6% (127/1 323) in 2005 to 24.1% (1 546/6 407) in 2014.The proportion of monotherapy decreased from 78.0% (1 032/1 323) in 2005 to 58.6% (3 757/6 407) in 2014. The proportion of two drugs combination increased from 20.0% (264/1 323) in 2005 to 26.7% (1 709/6 407) in 2014. The proportion of three drugs combination increased from 2.0% (26/1 323) in 2005 to 12.3% (788/6 407) in 2014. The proportion of four drugs combination increased from 0.1% (1/1 323) in 2005 to 2.3% (150/6 407) in 2014. Conclusions: The changes of the proportions of topical anti-glaucoma medications were remarkable from 2005 to 2014 in the outpatient of the Eye Hospital of Wenzhou Medical University. The ß-blockers and cholinergic agents were declining, while the prostaglandins, α(2)-agonists and carbonic anhydrase inhibitors were increasing, and the prostaglandins became the most prescribed medication since 2012. The proportion of combination therapy was increasing. (Chin J Ophthalmol, 2018, 54: 520-525).

Study of prevalence and influencing factors of depression in tumor patients and the therapeutic effects of fluoxetine.

OBJECTIVE: To observe the depression in patients with malignant tumor and influencing factors of the disease, as well as to investigate the effects of fluoxetine on depressive symptoms in cancer patients and the immune function. PATIENTS AND METHODS: 262 patients with malignant tumors, confirmed by pathological and radiological diagnosis as malignant tumor were randomly divided into 2 groups: the control group with chemotherapy; the treatment group with chemotherapy and 20 mg/d fluoxetine for six weeks. Before and after treatment, the scores of QLQ-C30 scale and changes of immune parameters were observed, including the determination of NK and T cell subsets. RESULTS: The prevalence of depression in cancer patients was not related to the tumor location. But gender, age, tumor stage, the income level of satisfaction and chronic cancer pain were related to the occurrence of depression in cancer patients (p < 0.05). In the fluoxetine treatment groups, by QLQ-C30 scores, in quality of life scores including body, function, social and cognitive function, and single symptoms including nausea, vomiting, constipation, diarrhea, and economic difficulties, the differences were not statistically significant. The QLQ-C30 scores of overall quality of life and emotional function were rising in the fluoxetine treatment group. The QLQ-C30 scores of the pain, shortness of breath, fatigue, loss of appetite, insomnia symptoms were decreased, which had a statistical significance (p < 0.05) compared with the control group. To compare with the control group, the scores of HAMD were decreasing in the fluoxetine treatment group, which had a statistical significance (p < 0.05). Before treatment, the NK cells, CD3+, CD4+, CD4+/CD8+ ratios of tumor patients decreased significantly, while CD8+ increased. After 6 weeks of treatment, NK cells, CD3+, CD4+, CD4+/CD8+ ratios increased significantly and CD8+ decreased. CONCLUSIONS: Sex, age, tumor stage, income satisfaction, and cancer pain were relevant factors in patients with tumor-associated depression. If depression can be detected in the early stage, and oral fluoxetine therapy can be conducted, it can improve the depression situation and immune function of patients with malignant tumor.

Characterising the variations in ethnic skin colours: a new calibrated data base for human skin.

BACKGROUND: Accurate skin colour measurements are important for numerous medical applications including the diagnosis and treatment of cutaneous disorders and the provision of maxillofacial soft tissue prostheses. METHODS: In this study, we obtained accurate skin colour measurements from four different ethnic groups (Caucasian, Chinese, Kurdish, Thai) and at four different body locations (Forehead, cheek, inner arm, back of hand) with a view of establishing a new skin colour database for medical and cosmetic applications. Skin colours are measured using a spectrophotometer and converted to a device-independent standard colour appearance space (CIELAB) where skin colour is expressed as values along the three dimensions: Lightness L*, Redness a* and Yellowness b*. Skin colour differences and variation are then evaluated as a function of ethnicity and body location. RESULTS: We report three main results: (1) When plotted in a standard colour appearance space (CIELAB), skin colour distributions for the four ethnic groups overlap significantly, although there are systematic mean differences. Between ethnicities, the most significant skin colour differences occur along the yellowness dimension, with Thai skin exhibiting the highest yellowness (b*) value and Caucasian skin the lowest value. Facial redness (a*) is invariant across the four ethnic groups. (2) Between different body locations, there are significant variations in redness (a*), with the forehead showing the highest redness value and the inner arm the lowest. (3) The colour gamut is smallest in the Chinese sample and largest in the Caucasian sample, with the Chinese gamut lying entirely the Caucasian gamut. Similarly, the largest variability in skin tones is found in the Caucasian group, and the smallest in the Chinese group. CONCLUSION: Broadly speaking, skin colour variation can be explained by two main factors: individual differences in lightness and yellowness are mostly due to ethnicity, whereas differences in redness are primarily due to different body locations. Variations in lightness are more idiosyncratic probably reflecting the large influence of environmental factors such as exposure to sun.

A phase II trial of dose-dense (biweekly) paclitaxel plus carboplatin as neoadjuvant chemotherapy for operable breast cancer.

The aim of the present study is to investigate the efficacy and safety of dose-dense (biweekly) carboplatin and paclitaxel as a neoadjuvant treatment for operable breast cancer. Patients with previously untreated breast cancer (stages Ic-III) were treated with four cycles of paclitaxel (175 mg/m(2), intravenous drip, D1) and carboplatin (area under the curve of 5, D1). Patients with HER2+ disease simultaneously received trastuzumab (6 mg/kg initial dose with subsequent doses of 4 mg/kg biweekly). The primary endpoint was a pathologically complete response (pCR). Between January 2012 and February 2014, 110 patients were enrolled. The overall pCR rate was 35.45 % (39 of 110). The pCR rates for the different cancer subtypes were as follows: 10.53 % (2 of 19) among the patients with the luminal A subtype, 12.50 % (5 of 40) among the patients with the luminal B (HER2-) subtype, 58.33 % (14 of 24) among the patients with the luminal B (HER2+) subtype, 57.14 % (8 of 14) among the patients with the triple-negative subtype, and 76.92 % (10 of 13) among the patients with the HER2+ subtype. The patients experienced the following toxicity side effects: grade 3/4 neutropenia (N = 27, 24.55 %), grade 3/4 anemia (N = 6, 5.45 %), grade 3/4 thrombocytopenia (N = 2, 1.82 %), grade 3 alanine aminotransferase (ALT) elevation (N = 1, 0.91 %), grade 3 neuropathy (N = 3, 2.73 %), grade 3 pain (N = 2, 1.82 %), and grade 3 fatigue (N = 1, 0.91 %). In total, 19.09 % of the patients experienced treatment delay or discontinuation due to hematological toxicity, and one patient discontinued treatment due to non-hematological toxicity. Neoadjuvant biweekly paclitaxel plus carboplatin is a feasible therapy that achieved high pCR rates in patients with the HER2+, triple-negative, and luminal B (HER2+) cancer subtypes (NCT0205986).

CBAP promotes thymocyte negative selection by facilitating T-cell receptor proximal signaling.

T-cell receptor (TCR)-transduced signaling is critical to thymocyte development at the CD4/CD8 double-positive stage, but the molecules involved in this process are not yet fully characterized. We previously demonstrated that GM-CSF/IL-3/IL-5 receptor common ß-chain-associated protein (CBAP) modulates ZAP70-mediated T-cell migration and adhesion. On the basis of the high expression of CBAP during thymocyte development, we investigated the function of CBAP in thymocyte development using a CBAP knockout mouse. CBAP-deficient mice showed normal early thymocyte development and positive selection. In contrast, several negative selection models (including TCR transgene, superantigen staphylococcal enterotoxin B, and anti-CD3 antibody treatment) revealed an attenuation of TCR-induced thymocyte deletion in CBAP knockout mice. This phenotype correlated with a reduced accumulation of BIM upon TCR crosslinking in CBAP-deficient thymocytes. Loss of CBAP led to reduced TCR-induced phosphorylation of proteins involved in both proximal and distal signaling events, including ZAP70, LAT, PLCγ1, and JNK1/2. Moreover, TCR-induced association of LAT signalosome components was reduced in CBAP-deficient thymocytes. Our data demonstrate that CBAP is a novel component in the TCR signaling pathway and modulates thymocyte apoptosis during negative selection.

Circulating tumor cells predict progression-free and overall survival in Chinese patients with metastatic breast cancer, HER2-positive or triple-negative (CBCSG004): a multicenter, double-blind, prospective trial.

BACKGROUND: The aim of this multicenter, double-blind, prospective study was to evaluate the potential utility of circulating tumor cell (CTC) measurements in predicting responses to anticancer therapies, including response to human epidermal growth factor receptor-2 (HER-2)-targeted agents, progression-free survival (PFS), and overall survival (OS) in Chinese women with metastatic breast cancer (MBC). PATIENTS AND METHODS: Three hundred MBC patients planned to complete three CTC blood draws and two imaging studies. RESULTS: A total of 294 of the 300 MBC patients enrolled from six leading Chinese cancer centers were assessable. In multivariate Cox regression analyses, the baseline CTC number remained an independent prognostic factor for PFS [hazard ratio (HR) = 1.93; 95% confidence interval (CI) = 1.39-2.69; P < 0.001) and OS (HR = 3.76; 95% CI = 2.35-6.01; P < 0.001). Similar results were observed for CTC counts at the first follow-up visit for both PFS (P = 0.049) and OS (P < 0.001). CONCLUSIONS: Enumeration of CTCs in Chinese MBC patients provides substantial prognostic information and is an independent factor associated with PFS and OS. Moreover, we demonstrated the prognostic value in the various disease subtypes, including HER-2-positive disease irrespective of therapy.

Protective effect of oleanolic acid against beta cell dysfunction and mitochondrial apoptosis: crucial role of ERK-NRF2 signaling pathway.

Pancreatic beta cell dysfunction is a hallmark of diabetes. Our previous results have shown that oleanolic acid (OA) has anti-diabetic potential. However, there is little literature reporting the effect of OA on beta cell dysfunction. The present study was designed to investigate the protective effect of OA against lipotoxicity and the underlying mechanisms. Lepr (db/db) diabetic mice were subjected to fasting blood glucose measurement, intraperitoneal glucose tolerance test after the administration of OA for two weeks. Histopathological observation was conducted by HE staining and transmission electron microscopy assay. Pancreatic islets were isolated from db/db diabetic mice and C57BL/6J mice. Palmitic acid (PA) was used to induce lipotoxicity in vitro. Apoptosis was evaluated in pancreatic islets in diabetic mice and in isolated pancreatic islets and beta-TC3 cells by TUNEL assay. Cellular ATP content, mitochondrial function and redox balance were examined. Phosphorylation of c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) and the activation of nuclear erythroid factor 2 p45-related factor 2 (Nrf2) signaling were evaluated by western blotting. In db/db mice, OA significantly protects beta cell function against lipotoxicity, evidenced by inhibition of apoptosis and improvement of glucose tolerance. In cells, OA administration may protect against PA-induced apoptosis and decrease of GSIS, in which process the activation of Nrf2 is essential. Once Nrf2 is activated, OA could induce GCLc expression, promote the production of GSH, and thus inhibit JNK phosphorylation and solid the antioxidant defense of mitochondria, leading to the inhibition of mitochondrial apoptosis. ERK signaling pathway is responsible for OA-induced activation of Nrf2 and the protective effect of OA. Overall, our study enhances the understanding of the protective effect of OA on beta cell and provides clues for further studies on the underlying mechanisms.

Accuracy and axilla sparing potentials of sentinel lymph node biopsy with methylene blue alone performed before versus after neoadjuvant chemotherapy in breast cancer: a single institution experience

INTRODUCTION: The timing of sentinel lymph node biopsy (SLNB) of breast cancer in the neoadjuvant setting is still controversial. We retrospectively analyzed a Chinese patient cohort with neoadjuvant chemotherapy (NAC) to evaluate the accuracy and axilla sparing potentials of different SLNB timings with methylene blue alone for lymphatic mapping. MATERIALS AND METHODS: Patients with NAC and axillary lymph node dissection (ALND) and either pre- or post-NAC SLNB were eligible. Clinicopathological characteristics, identification rate (IR), false-negative rate (FNR), accuracy, and positive-predictive value were calculated and compared between the pre- and post-NAC SLNB group using appropriate statistical methods. Axilla sparing potentials of different SLNB timings were evaluated and compared. RESULTS: One hundred and fifteen eligible cases were included, and 58 had pre-NAC SLNB while the other 57 had post-NAC SLNB. Both groups were comparable in clinicopathological characteristics, neoadjuvant treatments and pathologic complete response rate. IR, FNR, and accuracy of SLNB, as pre-NAC versus post-NAC, were 100 versus 98.2 % (P = 0.496), 0 versus 8.0 % (P = 0.181), and 100 versus 96.4 % (P = 0.239), respectively. Post-NAC SLNB had significantly higher positive-predictive value for ALNs than pre-NAC SLNB (70.0 vs. 36.4 %, P = 0.014), suggesting as high as 63.6 % of ALND performed in the pre-NAC group could have been avoided while only 30 % of ALND in the post-NAC group were theoretically unnecessary. CONCLUSIONS: Both SLNB timings of breast cancer patients with NAC were feasible and accurate. Although pre-NAC SLNB tends to be better in accuracy, post-NAC SLNB is significantly superior in terms of axilla sparing (AU)

Prognostic value of a mitochondrial functional score in prostate cancer.

OBJECTIVE: To evaluate the utility of a mitochondrial functional score in predicting the progress of prostate cancer. METHODS: This retrospective study included 72 patients (mean age 70.1 years) with prostate cancer who were treated by radical prostatectomy between October 2006 and March 2007. The epithelioglandular mitochondrial functional scores were assessed according to the Flameng grading. Patients were divided into six groups (groups 1-6) according to their Gleason score (Gleason score 2-7, respectively). The correlation between Gleason score and mitochondrial functional score was examined using Pearson's correlation coefficient. RESULTS: The mean mitochondrial functional score was significantly lower in group 6 compared with group 1. An inverse correlation was found between the Gleason and mitochondrial functional scores. At 1 year, significantly fewer patients in group 1 had died (0/15 patients) than in group 6 (2/10 patients); the deaths were cancer-related. CONCLUSIONS: Mitochondrial dysfunction exists in patients with prostate cancer, particularly in cases with a higher degree of malignancy. The mitochondrial functional score, combined with the Gleason score, is beneficial for predicting the progress of prostate cancer.

Structure and 1/f noise of boron doped polymorphous silicon films.

The influence of structure variation on the 1/f noise of nanometric boron doped hydrogenated polymorphous silicon (pm-Si:H) films was investigated. The films were grown by the conventional radio frequency plasma enhanced chemical vapor deposition (PECVD) method. Raman spectroscopy was used to reveal the crystalline volume fraction (X(c)) and crystal size of the pm-Si:H. The measurement of optical and structure properties was carried out with spectroscopic ellipsometry (SE) in the Tauc-Lorentz model. A Fourier transform infrared (FTIR) spectrometer was used to characterize the presence of nanostructure-sized silicon clusters in pm-Si:H film deposited on KBr substrate. The electrical properties of the films were measured using evaporated coplanar nickel as the electrode. A semiconductor system was designed to obtain the 1/f noise of pm-Si:H film as well as that of amorphous and microcrystalline silicon films. The results demonstrate that the 1/f noise of pm-Si:H is nearly as low as that of microcrystalline silicon and much lower than that of amorphous silicon. The disorder to order transition mechanism of crystallization was used to analyze the decrease of noise compared with amorphous silicon.

Remineralization effect of a low-concentration fluoride rinse in an intraoral model.

A previous study showed that a sodium hexafluorosilicate-calcium chloride-based two-solution fluoride (F) rinse containing 6 mmol/l of F was more effective than a 12 mmol/l F sodium fluoride rinse in depositing F on tooth surfaces and increasing oral F levels. The present study compared the remineralization effects of these two rinses in an intraoral de- and remineralization model. The results showed that the 6 mmol/l F two-solution rinse produced greater remineralization in increasing lesion mineral contents and reducing lesion depths. The results demonstrated that the effectiveness of an F regimen depends less on the F dose and more on the ability of the treatment to utilize F efficiently for remineralization.

Protection against lethal enterovirus 71 infection in newborn mice by passive immunization with subunit VP1 vaccines and inactivated virus.

Enterovirus 71 (EV71), the newest member of Enteroviridae, is notable for its etiological role in epidemics of severe neurological diseases in children. Developing effective vaccines is considered a top choice among all control measures. We compared the inactivated virus vaccine (10 microg protein/mouse) with subunit vaccines--VP1 DNA vaccine (100 microg/mouse) or recombinant VP1 protein (10 microg/mouse)--in its ability to elicit maternal antibody and to provide protection against lethal infection of EV71 in suckling mice. Prior to gestation, all three groups of vaccinated dams possessed similar levels of neutralizing antibody. With a challenge dose of 2300 LD(50) virus/mouse, suckling mice born to dams immunized with inactivated virus showed 80% survival. The subunit vaccines provided protection only at a lower challenge dosage of 230 LD(50) per mouse, with 40% survival for DNA vaccine and 80% survival for VP1 protein. The cytokine profile produced by splenocytes showed a high level of IL-4 in the inactivated virus group, high levels of IFN-gamma and IL-12 in the DNA vaccine group, and high levels of IL-10 and IFN-gamma in the VP1 protein group. Overall, the inactivated virus elicited a much greater magnitude of immune response than the subunit vaccines, including total IgG, all four IgG subtypes, and T-helper-cell responses; these antibodies were shown to be protective against lethal infection when passively transferred to susceptible newborn mice. Our data indicated that inactivated virus is the choice of vaccine preparation capable of fulfilling the demand for effective control, and that VP1 subunit vaccines remain promising vaccine strategies that require further refinement.

[Color measurements of 1,944 anterior teeth of people in southwest of China-discreption].

OBJECTIVE: To study the color distribution space of natural anterior tooth crowns of people in southwest China and effects of sex and age on tooth color. METHODS: The subjects studied consisted of 162 persons aged from 20 to 73 years and born in southwest China. A total of 1,944 healthy anterior teeth were measured in-vivo with a fiber-optical spectrophotometry system. RESULTS: Statistical analysis showed that the color distribution space of Chinese tooth crowns was wide. The value of L* varied from 42.383 to 67.428, the value of a* from -4.750 to 1.371, the value of b* from 1.88 to 20.268, the value of x from 0.298 to 0.393, the value of y from 0.332 to 0.392, and the value of Y from 19.383 to 34.025. The color difference between the upper and lower limits of 95% confidence was 31.667 CIE delta E units. The difference in colorimetry between male and female was not significant. The results showed that in three sections of teeth (incisal, middle and cervical) the values of L* and a* were negatively related to age (r < 0, P < 0.01); the value of b* was positively related to age just at the cervical and middle sites of teeth (r > 0, P < 0.01) and was not related to age at the incisal site of teeth (P > 0.05). CONCLUSION: The color distribution space of Chinese anterior tooth crowns is wide. There is no difference in the anterior tooth color between male and female subjects. The values of L* and a* and negatively related to age except the value of b*.