Time-dependent Expression of PEDF and VEGF in Blood Serum and Retina of Rats with Oxygen-induced Retinopathy

The effects of the balance changes of pigment epithelium growth factor(PEDF) and vascular endothelial growth factor(VEGF) in whole-body and retinal tissue on rats with oxygen-induced retinopathy were investigated. Forty-eight neonatal SD rats at the age of 7 days were randomly divided into 4 groups. The neonatal rats in experimental groups were exposed to 75% to 80% oxygen for 5 days and then to normal air, and those in control groups were kept feeding in normal air. At the age of 17 and 22 days, all the neonatal rats received retina angiography with FITC-dextran and the pathological changes of retinal vessels and perfusion were observed. HE staining of the tissue section and the number counting of endothelial cells extending beyond the inner limiting membrane were performed to evaluate the endothelial proliferation. Immunohistochemistry was applied to detect the expression of PEDF and VEGF in retinal tissue, and ELISA to detect their expression in serum. A hypoxic-ischemic proliferation of retina and more endothelial cells extending beyond the inner limiting membrane were found in the neonatal rats in both experimental groups of 17-day old and 22-day old as compared with those in control group with the difference being statistically significant(P<0.01). VEGF staining of the rats in the 17-day old experimental group was significantly stronger, with an increasing positive rate, than that of the rats in the 17-day old control group(P<0.01). PEDF staining of the rats of 22 days old was weaker than that of the rats of 17 days old in the experimental groups(P<0.01). There was no significant difference in serum VEGF concentration among all groups(P>0.05). The serum PEDF concentration in the rats of 17 days old in experimental group was decreased significantly as compared with that in the rats of 17 days old in control group(P<0.01), and in experimental groups, the serum PEDF concentration of the rats of 22 days old was increased as compared with that of the rats of 17 days old(P<0.01). In conclusion, the obviously decreased serum PEDF concentration and the abnormal enhanced expression of VEGF density in local retinal tissue broke down the balance of PEDF/VEGF in whole-body or local tissues, which might play an important role in retinal vascular proliferation.     

Insulin in endometrial carcinoma chemotherapy: A beneficial addition and not a problem

The effects of insulin or insulin in combination with chemotherapeutic drugs on the proliferation and apoptosis of endometrial carcinoma cells were examined with an aim to determine the efficacy and safety of insulin in endometrial cancer therapy.Ishikawa and Hec-1A cells were treated with insulin and/or paclitaxel.Cell proliferation was assessed by MTT assay.Cell cycle and cell apoptosis were determined by flow cytometry (FCM).Survivin gene expression was detected by RT-PCR.Our results showed that in a certain range of working concentrations and action time, insulin could mildly augment cell proliferation and the percentage of S phase cells in endometrial cancer (Ishikawa/Hec-1A) cells.Insulin plus paclitaxel (combination group) could significantly inhibit cell proliferation (69.38%±2.32% vs 40.31%±4.52% with Ishikawa; 64.11%±6.33% vs 45.89%±3.27% with Hec-1A) and increase cell apoptosis compared with treatment with paclitaxel alone (paclitaxel group).Survivin gene expression was also significantly decreased in combination group as compared with paclitaxel group.We are led to conclude that insulin can mildly augment cell proliferation and present chemotherapy sensitivity in endometrial cancer cells.Insulin can be to used safely and efficiently in endometrial cancer therapy.     

Functional status of pancreatic islet in acute leukemia.

Using enzymatic assay and radioimmunoassay, we studied the functional status of pancreatic islet in 50 patients with acute leukemia. Oral glucose tolerance test and insulin and C peptide release were made in 40 patients before and after treatment .14 patients who revealed diabetic curve and delayed insulin and C peptide release before treatment showed normal values in 6 after therapy. Five patients with impaired glucose tolerance and decreased insulin and C peptide release before treatment showed normalization of these parameters following therapy. Five patients with normal pretreatment values disclosed abnormal post-treatment results. The remaining 16 patients displayed normal results both before and after therapy. Anti-insulin antibodies were negative, and glucagon level was normal in all the 50 patients. The red cell insulin receptor binding rate analysed in 47 patients was significantly higher than in controls (P< 0.001). We considered that the disturbed glucose metabolism in acute leukemia was not     

Effect of a novel dietary supplement on pH levels of healthy volunteers： a pilot study

OBJECTIVE： To examine the effects of a greens alkalizing dietary supplement on urinary pH levels in individuals with lower-than-average pH levels. METHODS： The present study investigated the effects of an alkalizing formula （Reserveage Wholeganic GreensTM） on four individuals who had average urinary pH levels below 6.0 for three consecutive days. Following the three-day, baseline period, participants received Reserveage Wholeganic GreensTM for four consecutive days and were instructed to continue to measure their urine pH levels. Paired samples t-tests were used to examine pH levels before and after a four-day treatment period with Reserveage Wholeganic GreensTM. RESULTS： Compared to baseline, mean urine pH levels in all volunteers were significantly higher following the supplementation with Reserveage Wholeganic GreensTM （5.89 ±0.20 vs 5.56 ± 0.23; P〈0.01）. Participants＇ pH levels were also significantly higher than baseline on days 5, 6, and 7 of the treatment period （P 〈 0.05）. Noteworthy, on day 7, participants＇ mean pH levels were significantly higher than at the beginning of the treatment period （6.03 ± 0.15 at day 7 vs 5.65 ± 0.24 at day 4; P 〈 0.01）. CONCLUSION： The findings of this study suggest that supplementation with Reserveage Wholeganic GreensTM has an alkalizing effect on the body and can increase the urine pH levels in individuals with lower-than-average pH levels.     

Platelet activation in patients with chronic pulmonary heart disease. Effect of dipyridamole treatment.

Plasma levels of /f-thromboglobulin (/?-TG), platelet fac-tor 4(P and platelet aggregation rate (PAR) were measured in remission phase of 15 patients affected with chronic pulmonary heart disease (CPHD). 0-TG, /?-TG / PF4, PF4 and PAR were significantly higher in the patients than in controls (/3<0.01 and 0.05, respectively). After 10 days of treatment with Dipyridamole lOOtng tid, fi-TG, /?-TG / PF4 and PF4 decreased significantly compared with pretreatment values (/><0.01 and 0.05, respectively). The results suggest that in vivo platelet activation is indeed present in patients with CPHD and that dipyridamole can antagonize platelet activation in vivo.     

The Effect of Foods Containing Refined Konjac Meal on Human Lipid Metabolism

A total of 110 elderly people with hyperlipidemia were randomly assigned to one of two groups. The experimental group consumed an ordinary diet plus foods containing refined Konjac meal, and the control group consumed only the ordinary diet. The experiment was carried out for 45 days. The results indicate that for the experimental group blood levels of triglyeendes (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were significantly lowered (P < 0.01) at the end of the trial, whereas high-density lipoprotein cholesterol (HDL-C) and apoprotein (Al) levels were significantly elevated (P<0.01). In contrast, for the control group, the changes in the above parameters were insignificant. The differences in TC. TG, LDL-C, and HDL-C levels between the two groups were statistically significant. The effects of refined Konjac meal on lipid levels in the blood were somewhat different between patients with hyperlipidemia and subjects with risk critical values only. For the former, TG and TC were decreased by 83.8±133.5 mg/dl, and 42.4±23.4 mg/dl. respectively: but for the latter, they are decreased only by -1.1±23.1 mg/dl and 8.3± 18.2 mg/dl, respectively; the difference mentioned above is Statistically significant (P<0.01). 1990 Academic Press. Inc.     

EFFECTS OF CHINA-MADE RECOMBINANT HUMAN GROWTH HORMONE ON THE TREATMENT OF GROWTH HORMONE DEFICIENCY

Objective To evaluate the therapeutic effect of China-made recombinant human growth hormone (r-hGH) in children with growth hormone deficiency (GHD) and to investigate the utilities of various biochemical parameters in GHD diagnosis and treatment.Methods Our study comprises of 30 normal children and 71 GHD children treated with China-made r-hGH substitution 3 (IGFBP-3), bone turnover markers (Ost, ICTP), and anti-growth hormone antibody (GHAb) were detected before and after r-hGH treatment.Results After the first 3 and 6 months of treatment, growth velocities of GHD children were significantly increased (13.1 3.7 and 12.6 ± 3.6 cm/year) compared with pretreatment values (2.9 ± 0.8 cm/year, P ＜ 0.01). GHD Children had obviously reduced serum levels of IGF-1, IGFBP-3, and bone turnover markers (Ost, ICTP) compared with normal controls(P ＜ 0.01), and these biochemical parameters improved significantly after treatment (P ＜ 0.01). Growth hormone antibodies were positive in 17 of 45 cases after treatment by binding capacity detection. The binding percentage of growth hormone antibody which was increased more than 30% after the treatment showed a negative correlation with growth velocity (P ＜ 0.01).Conclusions (1) The growth stimulating effect and safety were confirmed in using China-made r-hGH in the treatment of GHD children for 6 months. (2) The measurements of serum IGF-1 and IGFBP-3 may serve as useful parameters in the diagnosis of GHD. (3) Serum Ost and ICTP are useful laboratory criteria for evaluating the effect of r-hGH therapy in the early stage. (4) It is necessary to monitor serum levels of GHAb during r-hGH therapy.     

Effect of Konjac Food on Blood Glucose Level in Patients with Diabetes

Seventy-two type II diabetic subjects were given Konjac food for 65 days. The data analyzed by multiple F test indicate that the fasting blood glucose (FBG) and the 2-h postprandial blood glucose (PBG) on the 30th and the 65th days after the food was ingested were significantly reduced (P = 0.001, P < 0.001, respectively), as was the glycosylated hemoglobin level at the end of the trial (P < 0.05). The final FBG and PBG of the subjects with initial FBG-O >200 mg% decreased on the average by 51.8 and 84.6 mg%. respectively; those with FBG-0 150-200 mg% decreased by 24.1 and 68.7 mg%; and those with FBG-O < 150 mg% decreased by 4.8 and 21.4 mg%. No significant changes in blood lipid indexes were observed, except that the triglycer-ide values of subjects with hypertriglyceridemia (>200 mg%) significantly decreased by 118.7 mg%. It was concluded that Konjac food is very useful in the prevention and treatment of hyperglycemia. (C)1990 Academic Press. Inc.     

A Study on Changes of Langerhans Cells in Human Epidermal Cell Culture

Human epidermal cells (ECs) were grown in vitro from normalhuman foreskin and the changes of Langerhans cells (LCs) within theoriginal explants and the epidermal outgrowth were observed in culturewith ATPase staining, HLA - Dr monoclonal antibody indirectimmuno-fluorescence and enzyme labelling avidin-biotin complex (ABC)staining. The capacity of ECs to stimulate the proliferation of allogeniclymhocytes was tested in the mixed skin-lymphocyte culture response(MSLR). The ATPase HLA-Dr positive LCs were gradually decreasedand significantly deformed within the original explants in culture. 70% ofLCs was decreased 3 days after culture. 90% of LCs was lost and the LCsremained in the original explants were only seen their outline 7 days afterculture. LCs approximatively disappeared within the original explants 14to 21 days after culture. The ATPase, HLA - Dr positive LCs have neverbeen found within the epidermal outgrowth. The ECs which were freshlyisolated from skin explants potently stimulated the proliferation ofallogenic lymphocytes in the MSLR. The ECs which were separated fromthe original explants after 3 days of culture were significantly declinedtheir ability to stimulate the proliferation of allogenic lymphocytes in theMSLR. The ECs separated from the original explants after 7 days ofculture were lost their ability to stimulate the proliferation of allogeniclymphocytes in the MSLR. The ECs separated from the epidermaloutgrowth failed to stimulate the proliferation of allogenic lymphocytes inthe MSLR. These results suggested that the ECs grown in our culturesystem were declined their immunogenety of skin allografts.     

Protective effect of an extract of Guipi Pill (归脾丸) against radiation-induced damage in mice

Objective:To study the protective effect of an extract of Guipi Pill(归脾丸) against radiationinduced damage.Methods:A total of 100 Kunming mice were randomly divided into normal group,model group,positive drug group(treated with radioprotective agent "523",5 mg/kg at 24 h before irradiation) and two treatment groups,with 20 mice in each group.The extract of water extraction-alcohol precipitation (WAP) from Guipi Pill were administered orally to the mice in the two treatment groups at the dose of 500 and 1,000 mg/kg,respectively,for 6 days prior to whole body radiation(8 Gy).Fifty mice with 10 in each group were used to observe the survival rate 30 days after radiation.The other 50 mice with 10 in each group were sacrificed on day 10 after radiation(6 Gy) in order to take blood,liver and unilateral femur.Results:Pretreatment prior to irradiation with WAP resulted in a significantly higher 30-day survival rate of mice after exposure to a potentially lethal dose of 8-Gy radiation.WAP could significantly increase the total white blood cell count and DNA content of bone marrow,and it also increased the activity of various antioxidant enzymes,such as superoxide dismutase,catalase,total antioxidant capacity and glutathione peroxidase in liver tissue of mice, which were reduced by radiation treatment.Maleic dialdehyde level and bone marrow micronucleus rate were significantly reduced by WAP,which were increased after 6-Gy radiation.Conclusion:WAP of Guipi Pill could increase the 30-day survival rate and the antioxidant capacity as well as protect bone marrow in mice.WAP of Guipi Pill is an effective radioprotective agent.     

Efficacy of Subcutaneous Administration of Gonadotropin-releasing Hormone Agonist on Idiopathic Central Precocious Puberty

In order to assess the feasibility of subcutaneous administration of Triptorelin with 6-week intervals for the suppression of pituitary-gonadal axis and changes of clinical signs in girls with idiopathic central precocious puberty (ICPP), 46 girls with ICPP were treated with GnRHa. Triptorelin (Decapeptyl, 3.75 mg) was administered subcutaneously (SC) at 6-weeks intervals or intramuscularly (IM) at 4-weeks intervals randomly for more than 12 months consecutively. During GnRHa therapy, clinical parameters and laboratory data, including height, weight, pubertal stage, bone age, uterine volume and ovarian size, serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2), were monitored and analyzed. It was found that both treatment regimes led to regression of precocious puberty and reversal of secondary sexual characteristics. Breast developments regressed. Uterine volume was decreased after treatment, but there was no statistically significant difference. Mean ovarian volume did not change significantly during treatment. The height velocity was decreased significantly from 6.3±1.4 cm/year to 5.8±1.2 cm/year in group SC and 6.7±1.3 cm/year to 5.4±1.0 cm/year in group IM, respectively. The rate of bone maturation was reduced significantly during treatment. The ratio of deltaBA/deltaCA was 1.2±0.2 or 1.3±0.3 at the onset of therapy and decreased significantly after the treatment to 0.7±0.2 or 0.9±0.1, respectively. The predicted adult height was increased significantly and progressively during therapy. The levels of serum LH, FSH and E2 returned to the prepubertal condition. No significant side effects of therapy were noted. The most common side effect during SC treatment was that a non-irritating, 1 cm in diameter mass was palpated at the site of subcutaneous injection in the abdominal wall of patients, which disappeared after 6-12 weeks. Two girls had minimal withdrawal vaginal bleeding episodes after the first injection. It was concluded that both IM and SC triptorelin administrations were clinically effective. They induce profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing height velocity, slowing bone maturation and increasing predicted adult height. These results suggest that subcutaneous injection of triptorelin in 6-weeks intervals at a dosage of 3.75 mg be a safe and acceptable regimen for ICPP     

3,4—Methylenedioxymethamphetamine（MDMA） Abuse Markedly Inhibits Acetylcholinesterase Activity and Induces Severe Oxidative Damage and Liperoxidative Damage

Objective To investigate whether 3,4-methylenedioxymethamphetamine (MDMA) abuse produces another neurotoxicity which may significantly inhibit the acetylcholinesterase activity and result in severe oxidative damage and liperoxidative damage to MDMA abusers. Methods 120 MDMA abusers (MA) and 120 healthy volunteers (HV) were enrolled in an independent sample control design, in which the levels of lipoperoxide (LPO) in plasma and erythrocytes as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and acetylcholinesterase (AChE) in erythrocytes were determined by spectrophotometric methods. Results Compared with the average values of biochemical parameters in the HV group, those of LPO in plasma and erythrocytes in the MA group were significantly increased (P<0.0001), while those of SOD, CAT, GPX and AChE in erythrocytes in the MA group were significantly decreased (P<0.0001). The Pearson product-moment correlation analysis between the values of AChE and bioche     

Burn and Damage by Lipid Peroxidation

In this study,the plasma and erythrocyte(RBC)lipoperoxidation rates,the contents of antioxidant vitamin E(VE)and the activities of antioxidationenzyme SeGSHP_x of plasma and RBC in the patients with burn were determinedon the 1st,3rd,5th,10th and 15th days after burn.The results showed that ascompared with healthy subjects,the contents of Iipoperoxide were increased,and thelevels of VE and the activities of SeGSHP_x were decreased significantly.Thechanges became more significant with the time elapsing,and the most significantchanges were on the 10tb days postburn.In the meantime the percentages of RBCspontaneous hemolysis and the activities of SeGSHPx were increased,and thecontents of VE in RBC were decreased markedly.The regularity of the changes inthe lipoperoxidation rates of plasma and RBC was in accordance with that in thecontents of VE in them.The degrees of the changes in the LPO and VE contentsand the SeGSHPx activities in plasma were in relation to the extents of burn.Onthe 53th,65th and 85th days during recovery postburn,the changes were stillsignificant compared to the healthy subjects,although they had a tendency torestore.     

Measurement of Pulmonary Diffusing Capacity for Carbon Monoxide(D_LCO)in Application to Chronic Obstructive Pulmonary Diseases

The pulmonary diffusing capacity for carbon monoxide(D_LCO)was measuredin 50 normal subjects,50 patients with emphysema and 31 with asthma.The results sh-owed that the D_LCO value of the asthma group was markedly higher than that of thehealthy group,while the D_LCO/pr% and KCO values of the asthma group were similarto those of the healthy group.The values of D_LCO,D_LCO/pr% and KCO in the emphy-sema group were very significantly lower than those in the asthma and healthy groups.Our study suggests that the measurement of D_LCO is onc of the useful pulmonary func-tion tests in differentiation of emphysema from asthma.The mechanism ofdiffcrcnt D_LCOvalues between emphysema and asthma is discussed.The D_LCO values in patients withmild to severe emphysema gradually decreased with the severity of emphysema.The KCOvalues between the mild emphysema and healthy groups were dramatically different.Thisis helpful in the early diagnosis of emphysma as combined with other clinical data.     

Effect of Puerarin on the Pharmacokinetics of Baicalin in Gegen Qinlian Decoction (葛根芩连汤) in Mice

Objective: To study the pharmacokinetics of puerarin(PUE) in Gegen Qinlian Decoction(葛根芩连汤, GQD), and the effects of PUE dosage variations on the pharmacokinetics of baicalin(BAL) in mice. Methods: GQD is composed of the concentrated granules of four Chinese herbs. Three dosages with different levels of PUE, including GQD, GQD co-administered with PUE, and GQD co-administration with two times the amount of PUE, were used to research the pharmacokinetics of PUE and BAL in mice. The indirect competitive enzyme-linked immunosorbent assay(ic ELISA) methods based on an anti PUE-monoclonal antibody(MAb) and BAL-MAb were employed to determine the concentration of PUE and BAL in mice blood. Results: After the co-administration of GQD with PUE, the area under the curves(AUC0-14 h) of PUE increased 2.8 times compared with GQD. At the dose of GQD co-administration at two times that of PUE, the AUC0-14 h of PUE was almost equal to that of GQD co-administration of PUE, showing non-linear pharmacokinetics. The AUC0-48 h of BAL showed a good dose-related increase of PUE(r=0.993) in the range from 100 to 300 mg/kg, indicating that PUE dramatically affects the absorption of BAL in mice. There was no significant difference in the other pharmacokinetic parameters, such as the first time of maximum concentration(Tmax), the second Tmax, or the mean residence time. Conclusions: The ic ELISA methods were successfully applied to pharmacokinetic studies of PUE and BAL in GQD in mice. The dosage variability of PUE of the main ingredient in GQD affects its own pharmacokinetic characteristics and the absorption characteristics of BAL.     

Neurogenesis by Activation of Inherent Neural Stem Cells in the Rat Hippocampus after Cerebral Infarction

Objective To investigate the changes of neural stem cells （NSCs） in the rat hippocampus after cerebral infarction （CI） and to evaluate the neurogenesis caused by the activation of NSCs. Methods CI models of rats were made and rats were assigned to 6 groups： sham-operated, 1 day, 3 days, 7 days, 14 days, and 28 days after CI. The dynamic expression of bromodeoxyuridine （BrdU）, polysialylated neural cell adhesion molecule （PSA-NCAM）, glial fibrillary acidic protein （GFAP）, and neuronal nuclear antigen （NeuN） were determined by immunohistochemistry and immunofluorescence staining. BrdU was used to mark the proliferated NSCs. PSA-NCAM was used to mark the plasticity of activated NSCs. GFAP and NeuN were used to mark the differentiated NSCs. Results Compared with the controls, the number of BrdU^＋ cells in the hippocampus increased significantly at 1 day after CI（P〈0.05）, reached peak at 7 days after CI （P〈0.05）, decreased but still elevated compared with the controls at 14 days after CI （P 〈 0.05）, and nearly unchanged at 28 days after CI. The number of Brd^U＋/PSA-NCAM^＋ cells increased significantly at 7 days after CI （P〈0.05）, reached peak at 14 days after CI （P 〈 0.05）, and decreased but still elevated compared with the controls at 28 days after CI （P 〈 0.05）. The number of BrdU^＋/PSA-NCAM^＋ cells was equal to 60% of the number of BrdU^＋ cells in all the same period. The number of BrdU^＋/NeuN^＋ cells in the hippocampus increased significantly at 14 days after CI （P 〈 0.05） and reached peak at 28 day after CI （P 〈 0.05）. The number of BrdU^＋/GFAP^＋ cells in the hippocampus nearly unchanged after CI. Conclusion CI can stimulate the proliferation of inherent NSCs, and most proliferated NSCs may differentiate into neurons and represent neural plasticity.     

Hepcidin-orchestrated Hemogram and Iron Homeostatic Patterns in Two Models of Subchronic Hepatic injury

Objective This study was designed to evaluate hematological disorders and the orchestrating roles of hepcidin and IL-6 in rat models of thioacetamide(TAA) and carbon tetrachloride(CCl_4) hepatotoxicity. Methods Rats were intraperitoneally injected with TAA(10 mg/100 g rat weight dissolved in isosaline) or CCl_4(100 μL/100 g rat weight diluted as 1:4 in corn oil) twice weekly for eight consecutive weeks to induce subchronic liver fibrosis. Blood and tissue samples were collected and analyzed. Results CCl_4 but not TAA significantly decreased the RBCs, Hb, PCV, and MCV values with minimal alterations in other erythrocytic indices. Both hepatotoxins showed leukocytosis, granulocytosis, and thrombocytopenia. By the end of the experiment, the erythropoietin level increased in the CCl_4 model. The serum iron, UIBC, TIBC, transferrin saturation%, and serum transferrin concentration values significantly decreased, whereas that of ferritin increased in the CCl_4 model. TAA increased the iron parameters toward iron overload. RT-PCR analysis revealed increased expression of hepatic hepcidin and IL-6 m RNAs in the CCl_4 model and suppressed hepcidin expression without significant effect on IL-6 in the TAA model. Conclusion These data suggest differences driven by hepcidin and IL-6 expression between CCl_4 and TAA liver fibrosis models and are of clinical importance for diagnosis and therapeutics of liver diseases.     

Changes of cellular morphology and nuclear DNA content in different nasopharyngeal epithelium from different patients.

Cellular morphology and nuclear DNA content were measured with point-counting technique and flow cytometry (FCM) respectively in normal nasopharyngeal epithelium (NE), tissue adjacent to carcinoma (ATC) and nasopharyngeal carcinoma (NPC). The results showed that all 20 patients with NE show ed diploid, whereas 38 (38%) of 101 patients with NPC, 7 (58%) of 12 patients with recurrent NPC, 6 (30%) of 20 patients with ATC and 2 (33%) of 6 patients with NE positive to EBVCA-IgA test showed nondiploid. A total of 19 morphometric parameters of the cell were measured and calculated. The results showed that with malignant transformation of NE, most of the cellular morphometric parameters gradually increased in numerical values while no marked difference was shown between normal NE and simple hyperplasia or metaplasia in terms of cytomorphometric characteristics. Most of the parameters in dysplasia changed significantly as compared with those normal NE, simple hyperplasia or metaplasia and NPC groups. Cytomorphome