[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).

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).

[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.

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.

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.

Positive selection determines T cell receptor V beta 14 gene usage by CD8+ T cells.

We report here a mAb, 14-2, reactive with TCRs that include V beta 14. The frequency of V beta 14+ T cells varies with CD4 and CD8 subset and is controlled by the H-2 genes. Thus CD8+ T cells from H-2b mice include approximately 2.3% V beta 14+ T cells while CD8+ T cells from mice expressing K kappa include greater than 8% V beta 14+ T cells. In all strains examined, 7-8% of CD4+ T cells express V beta 14. The frequent usage of V beta 14 in CD8+ T cells of K kappa-expressing mice is a result of preferential positive selection of V beta 14+ CD8+ T cells as demonstrated by analysis of radiation chimeras. These studies demonstrate that H-2-dependent positive selection occurs in unmanipulated mice. Furthermore, the results imply that positive selection, and possibly H-2 restriction, can be strongly influenced by a V beta domain, with some independence from the beta-junctional sequence and alpha chain.

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.

[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.

MHC class I deficiency: susceptibility to natural killer (NK) cells and impaired NK activity.

The role of major histocompatibility complex (MHC) class I expression in natural killer (NK) cell target recognition is controversial. Normal T cell blasts from MHC class I-deficient mutant mice were found to serve as target cells for NK cells in vitro, which suggests that MHC class I molecules are directly involved in NK cell recognition. Spleen cells from the mutant mice were deficient in their ability to lyse MHC class I-deficient target cells or NK-susceptible tumor targets, and mutant mice could not reject allogeneic bone marrow. Thus, class I molecules may participate in the positive selection or tolerance induction of NK cells.

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.

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.

Granulocyte-macrophage colony-stimulating factor primes phospholipase D activity in human neutrophils in vitro: role of calcium, G-proteins and tyrosine kinases.

The addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) to human peripheral blood neutrophils primes phospholipase D (PLD) to subsequent stimulation by N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA). The present investigation was directed at the elucidation of the pathway(s) involved in the regulation of the activity of PLD in untreated as well as in GM-CSF-primed neutrophils. Pretreatment with pertussis toxin (PT) totally inhibited fMLP-induced activation of PLD in control or GM-CSF-treated cells. PT did not affect the activation of PLD by PMA but inhibited the priming effect of GM-CSF. Activation of PLD by fMLP was dose-dependently inhibited by erbstatin, an inhibitor of tyrosine kinases. Furthermore, pre-incubation with GM-CSF accelerated the tyrosine phosphorylation response to fMLP (as analysed by protein immunoblot with antiphosphotyrosine antibodies). In PMA-stimulated neutrophils, erbstatin antagonized the priming effect of GM-CSF on PLD without affecting the direct effects of the phorbol ester. Buffering cytoplasmic calcium with the chelator BAPTA inhibited fMLP-induced activation of PLD as monitored by the formation of phosphatidylethanol. The stimulation of PLD by PMA was partially attenuated in BAPTA-loaded cells while the priming effect of GM-CSF was abolished. Thus, priming of human neutrophil PLD by GM-CSF may be mediated by G-proteins, by increases in the levels of cytosolic free calcium, and by stimulation of protein kinase C and/or tyrosine kinase(s).

Transgenic mice expressing surface markers for IFN-gamma and IL-4 producing cells.

The detection of T(H)1-type and T(H)2-type cells directly in situ would be of great value in the study of T(H) development and function in vivo. Transgenic mice expressing human Thy1 and mouse Thy1.1 under the control of the murine IFN-gamma and IL-4 promoters, respectively, have been generated. The hThy1(+) cells represent (with some temporal lag) most of the IFN-gamma-producing CD4(+) T-cells, while the mThy1.1(+) cells represent only a percentage of IL-4 secreting cells. This may be due to mono-allelic expression of the IFN-gamma and IL-4 genes. Since permeabilization is not required for the detection of the transgenic surface markers, these transgenic mice can facilitate the detection of T(H)1-type and T(H)2-type cells by flow cytometry with surface immunofluorescent staining. These surface markers should permit isolation of viable cells according to their T(H) type for adoptive transfer experiments, and may serve as a model system for tracing the development of T(H)1 and T(H)2-type cells in vivo.

Release of pro-thyrotropin-releasing hormone connecting peptides PS4 and PS5 from perifused rat hypothalamic slices.

Thyrotropin-releasing hormone prohormone contains five copies of the thyrotropin-releasing hormone progenitor sequence Gln-His-Pro-Gly, each flanked by pairs of basic amino acids and separated by intervening sequences (connecting peptides). Using a perifusion system for rat hypothalamic slices, we have studied the ionic mechanisms underlying the release of two connecting peptides originating from the thyrotropin-releasing hormone precursor: prepro-thyrotropin-releasing hormone-(160-169) (Ps4) and prepro-thyrotropin-releasing hormone-(178-199) (Ps5). Quantification of these two peptides in the effluent fluid was performed using sensitive and highly specific radioimmunoassay procedures. Reverse phase high performance liquid chromatography analysis of the effluent perifusate showed that released peptides co-eluted with synthetic Ps4 and Ps5. The secretion of Ps4 and Ps5 was stimulated by depolarizing agents such as (i) high potassium concentrations, (ii) ouabain, an Na+/K(+)-ATPase inhibitor, and (iii) veratridine, a stimulator of voltage-operated Na+ channels. The response to potassium (70 mM) was not affected by the specific Na+ channel blocker tetrodotoxin. The K+ channel blocker tetraethylammonium did not modify K(+)-evoked release of Ps4 and Ps5. These data suggest that voltage-operated Na+ channels are not involved in the stimulatory effect of high K+ on the release of Ps4 and Ps5. The lack of effect of picrotoxin, a Cl- channel blocker, on the secretion of the connecting peptides indicates that chloride ions play a minor role in the release process. In contrast, deprivation of Ca2+ in the perifusion medium suppressed K(+)-evoked release of the two peptides, indicating that voltage-operated Ca2+ channels are implicated in the release process. Taken together, the present results show that non-thyrotropin-releasing hormone peptides originating from the thyrotropin-releasing hormone precursor are secreted by mediobasal hypothalamic fragments. The release of these peptides is stimulated by depolarization through a calcium-dependent process. These data indicate that Ps4 and Ps5 may be released at the level of the median eminence into the portal circulation, suggesting that these peptides may play a role in the control of anterior pituitary cells.

Distribution of estrogen receptors in the rat pituitary as studied by in situ hybridization.

The localization of estrogen receptors in the rat pituitary gland was performed by in situ hybridization. The probe used was a synthetic oligonucleotide probe labelled with 35S complementary to the mRNA coding for a fragment (1-24) of estrogen receptor. Strong labelling was observed in cells of the anterior and intermediate lobes whereas the posterior lobe remains unlabelled. These results suggest that not only the anterior lobe but also the intermediate lobe is a target for estrogens.

Neuroanatomical connections between corticotropin-releasing factor (CRF) and somatostatin (SRIF) nerve endings and thyrotropin-releasing hormone (TRH) neurons in the paraventricular nucleus of rat hypothalamus.

In order to investigate the possible involvement of corticotropin-releasing factor (CRF) and somatostatin (SRIF) on thyrotropin-releasing hormone (TRH) neuronal cell activity in the rat hypothalamic paraventricular nucleus, we have proceeded to the simultaneous localization of CRF or SRIF and TRH. For this purpose, we used a dual immunostaining procedure that employed antibodies to CRF and SRIF and peroxidase-labeled goat anti-rabbit IgG as a first sequence, and antibodies to a cryptic fragment (Phe178-Glu199) of pro-TRH (to label TRH neurons) and alkaline phosphatase-labeled goat anti-rabbit IgG as the second sequence. A rich innervation of the paraventricular nucleus by immunoreactive CRF and SRIF fibers was observed. A large number of CRF and SRIF nerve endings were seen intimate anatomic proximity and often appeared to surround TRH-containing cell bodies. These results strongly suggest that TRH neurons might be regulated by both CRF and SRIF. These interactions might be the neuroanatomical basis for the already observed inhibitory effects of CRF and SRIF on TRH release.

Immunoelectron microscopic localization of thyrotropin-releasing hormone (TRH) precursor in the rat raphe nuclei.

Using antisera to two pro-thyrotropin-releasing hormone (pro-TRH)-derived cryptic peptides, we have studies by immunocytochemistry the ultrastructural localization of pro-TRH in the rat raphe nuclei. The same results were obtained with both antisera. Immunostaining was found in cell bodies, dendrites and endings. In cell bodies, the reaction product was restricted to Golgi saccules and dense core vesicles which were very few in number. In dendrites, the staining was rather diffuse without any association with specific organelles. These results suggest that the Golgi apparatus might be involved in pro-TRH processing.