Biomedical subjects

S Wang

Publications and source records attributed to S Wang.

At least 343 records · Page 19Linked to original sources

PubMed2001

[An experimental study on the relationship between early myocardial injury and the in situ expression of TNFalpha mRNA in burned rats with endotoxemia].

OBJECTIVE: To observe the in situ expression of TNF mRNA and protein in myocardial cell, so as to explore the possible mechanism of early myocardial injury in scalded rats with endotoxemia. METHODS: One hundred and seventy eight Wistar rats inflicted with 20% TBSA III degree napalm burn compound with endotoxemia and multiple organ injury were employed as the model and were randomly divided into four groups as follow. (1) burn and infusion group (BI): the rats were burned and infused with endotoxin. (2) simple burn group (S): the rats were burned only. (3) simple endotoxin infusion group (EI): the rats were only infused with endotoxin. (4) normal control (C). The observation time points were designed to be 0.5, 1, 3, 6, 12, 24 and 48 postburn hours (PBH). The morphological and functional changes in rat myocardium, the change in serum TNFalpha, the cellular location and distribution of TNFalpha mRNA and proteins were observed by light microscope (LM), electronic microscope (EM), ELISA, immunohistochemistry and in situ hybridization staining. RESULTS: There exhibited a series of pathomorphological changes in the myocardium at early postburn stage in rats of BI group, such as wavy degeneration of myocardial fibers, the formation of contractile bands, fragmentation of myocardial fibers and focal cytoplasmic lysis, etc. The left ventricular systolic pressure (LVSP) and the maximum change rate of intraventricular pressure (plus minus dp/dtmax) decreased significantly (P < 0.01). Serum TNFalpha level increased obviously at 1 PBH (P < 0.01) and peaked at 3 similar 6 PBH. It was found that TNFalpha mRNA was principally located in myocardial cells and in a part of inflammatory cells. But these milder pathomorphological changes in myocardial injury were found in rats of S and EI groups. In addition, there appeared elapsed TNFalpha peak values and relative weaker expression of myocardial TNFalpha mRNA. CONCLUSION: TNFalpha mRNA and protein could be expressed in myocardium in burned rats with endotoxemia which might be one of the origins of TNF in participating in the development of early postburn myocardial structural and functional injury.

Animals↗

PubMed2001

[The Influence of stress inhibition on the plasma levels of LPS, pro-inflammatory and Th1/Th2 cytokines in severely scalded rats].

OBJECTIVE: To explore the influence of stress inhibition on the plasma levels of LPS pro-inflammatory and Th1/Th2 cytokines in severely scalded rats. METHODS: Sprague-Dawley (SD) rats inflicted by 30% TBSA of deep partial thickness burn were employed as the model and randomly divided into burn with immediate resuscitation (A) and burn with immediate resuscitation and soluble cocktail (B) groups. Plasma was harvested from peripheral blood at different postburn time points for the determination of the levels of LPS, IL-1alpha, IL-6, TNFalpha, IL-8, IL-2, IFN-gamma, IL-4 and IL-10 in the rats of the two groups. And the rats inflicted by sham scalding were taken as control group (C). RESULTS: The postburn plasma levels of LPS, IL-1alpha, IL-4 and IL-10 increased gradually, while the plasma levels of IL-6, TNF, IL-8, IL-2 and IFN increased initially and decreased thereafter. The increasing ranges of LPS and these inflammatory cytokines were higher in A group, in which the increases of IL-1alpha, IL-6 and IL-4 appeared earlier in A (6 PBH) than those in B (12 PBH) groups. CONCLUSION: Prompt fluid resuscitation and stress inhibition could delay and ameliorate the postburn inflammatory reaction, decrease the production of Th2 cytokine and partially restore the production of Th1 cytokine after 48 PBH.

Animals↗

PubMed2001

[The relationship between postburn enterogenic hypermetabolism and decontamination of intestine].

OBJECTIVE: To explore whether postburn enterogenic hypermetabolism exists. METHODS: Eighty -- eight Wistar rats inflicted by 30% TBSA III degree burns were randomly divided into two groups, i,e. burn (B) and burn with gut decontamination (D) groups. The change in resting energy expenditure (REE) was observed during 0 to 10 postburn day (PBDs) in rats. The plasma contents of lipopolysaccharide (LPS), tumor necrosis factor (TNF) and interleukin-1 (IL-1) were determined on 1, 3, 5, 7 and 10 PBDs and their correlations were analyzed. RESULTS: The postburn REE and plasma contents of TNF, LPS and IL-1 were much higher in both groups than those before injury. When compared between the two groups, the above data in D group were lower in varying degrees than those in B group. It was shown by correlation analysis that REE was postively correlated to LPS, TNF and IL-1, respectively (gamma = 0.77 similar 0.9, P < 0.05 similar 0.01). CONCLUSION: Postburn hypermetabolism in rats could be ameliorated by gut decontamination, and the postburn plasma inflammatory mediators in rats could also be lowered by gut decontmination. This suggests that enterogenic hypermetabolism does exist after burn injury.

Animals↗

PubMed2001

[An experimental study on the effects of early postburn nutrition on calcitonin gene--related peptide].

OBJECTIVE: To explore the resuscitation effects of different nutritional routes during early postburn stage on intestinal tract, and the relationship between calcitonin gene -- related peptide (CGRP) and resuscitation of intestinal tract. METHODS: Sixty Wistar rats inflicted by 30% TBSA III degree flame burn were randomly divided into burn with enteral feeding group (EF, 30 rats) and burn with early parenteral nutrition group (EPN group, 30 rats). Six normal rats without burn injury served as control group (C). The changes in general condition, intestinal mucosal blood flow, plasma concentration of CGRP immunologic competence substance and intestinal CGRP positive staining substance in the rats were observed at 6, 12, 24, 48 and 72 postburn hours (PBHs). RESULTS: The rat intestinal mucosal blood flow decreased postburn, especially in EPN group (P < 0.05). The postburn plasma CGRP increased and the plasma CGRP level in EF group was obviously lower than that in EPN group at 72 PBH (P < 0.01). The CGRP positive staining cells of intestinal tract decreased markedly postburn (P < 0.05) in both burn groups, and those in EPN were significantly lower abundant than those in EF group at 24 and 48 PBHs (P < 0.05). Furthermore, the decrease in intestinal mucosal blood flow was positively related to the decrease in intestinal intramuscular nerve plexus CGRP (r = 0.72, P < 0.05). CONCLUSION: Enteral nutrition exerted better effects on early postburn intestinal resuscitation than parenteral nutrition. The decrease in intestinal blood supply might be mainly due to the excessive increase in plasma CGRP immune active substance and the decrease of postburn intestinal tract CGRP immunologic competence substance. Early enteral feeding might play resuscitative role by modulating CGRP.

Animals↗

PubMed2001

[An experimental study of the effects of early enteral feeding of L--arginine enriched food on postburn intestinal mucosal proliferation in rats].

OBJECTIVE: To investigate the effects of early enteral feeding of L -- arginine enriched food on postburn intestinal mucosal proliferation in rats. METHODS: Twenty Wistar rats prepared with gastrostomy 7 days before the experiment were inflicted by 30% TBSA flame burn, and were divided into early enteral feeding (EF), L -- arginine enriched early enteral feeding group (AEF) receiving feeding from 2 PBHs and delayed feeding (DF) group, receiving feeding from 48 PBHs. The changes in intestinal mucosal DNA content and intestinal mucosal proliferating cell nuclear antigen labeling index (PCNALI) were determined on the 1st, 3rd, 6th and 9th postburn days (PBDs) respectively in rats. RESULTS: There were rare intestinal mucosal PCNA positive cells on the 1st PBD in all groups. Compared with that in DF group, the intesinal mucosal PCNALI in AEF group increased obviously on 3 PBD, while that in EF group increased evidently on 6 PBD. (P < 0.05). CONCLUSION: There existed intestinal mucosal injury postburn as shown by the inhibition of intestinal epithelial proliferation. Early enteral feeding with L -- arginine enriched food could not only ameliorate intestinal mucosal injury, but also enhance the proliferation of intestinal mucosal epithelium.

Animals↗

PubMed2001

[Thrombopoietic effect of recombinant human thrombopoietin gene transferred to mice mediated by electric pulse on normal and experimental thrombocytopenia mice].

OBJECTIVE: To investigate the thrombopoietic effect of recombinant human thrombopoietin (rhTpo) gene transferred by electric pulse to normal and experimental thrombocytopenia mice. METHODS: Eukaryotic high expressing plasmid pcDI/Tpo was constructed by gene recombinant technology. 200 microg of the recombinant plasmid was injected into quadriceps femoris muscle of normal and experimental thrombocytopenia mice. Six times of electric pulse at 100v, 1Hz, 40ms were given immediately after the injection.The expression of rhTpo gene and its protein were assayed by RT-PCR and Western Blotting, respectively. Serum Tpo concentration was assayed by ELISA method. RESULTS: The recombinant plasmid pcDI/Tpo was successfully constructed. The expression of mRNA and protein of rhTpo gene was detected in the skeletal muscle of mice after transfection. Serum Tpo level increased from 328 +/- 89 ng/L to 1185 +/- 264 ng/L, and the platelet level of transfected mice increased from (259 +/- 27) x 10(9)/L to (640 +/- 31) x 10(9)/L. After injection with carboplatin, the platelet level decreased, but the nadir point was higher in pcDI/Tpo group than that in control group, and the recovery time of platelet count in pcDI/Tpo group shortened. CONCLUSION: The rhTpo gene could be effectively transfected to mice by electric pulse and played thrombopoietic role in vivo.

Animals↗

PubMed2001

[A novel rat aplastic anemia model induced by 5-fluorouracil combined with busulfan].

OBJECTIVE: To develop an aplastic anemia model with hematopoietic stem cell failure in rats. METHODS: Normal Wistar rats were injected i.p. with 5-fluorouracil and 5 days later p.o. by busulfan once a week for 3 times. A 5-FU alone group and a busulfan alone group were as control. The parameters tested indices were as following: incidence and mortality of aplastic anemia rats, blood picture, bone marrow nucleated cell count, CFU-GM of bone marrow cells and histology of hematopoietic organs. RESULTS: In the 5-FU plus busulfan group, the incidence of acute aplastic anemia was 82.0% (40/49 rats), the average survival time was (30.0 +/- 6.5) days. The remained 9 rats developed chronic aplastic anemia (18.0%). The total incidence of aplastic anemia was 100%, and the mortality was 98%. The blood cells count of the aplastic anemia rats was gradually reduced to a level of half the premedications and no CFU-GM was detected, and the patho-morphological examination showed that the bone marrow was replaced by fat cells, and the lymphoid tissue of spleen, thymus and lymph-nodes were remarkably atrophied without extra-medullary hematopoiesis. The control group (5-FU treated) developed a transient hematopoiesis suppression, and recovered rapidly to normal. Three of 12 rats in the busulfan treated group developed aplastic anemia. CONCLUSION: 5-FU combined with busulfan could impair the hematopoietic stem cells and resulted in an irreversible aplastic anemia in rats, making a rat aplastic anemia model with hematopoietic stem cell failure.

Anemia, Aplastic↗

PubMed2001

[The experimental study of transfected sFlt-Ig gene on K562 leukemia cell growth in nude mice].

OBJECTIVE: To observe the influence of transfected soluble vascular endothelial growth factor (VEGF) receptor (sFlt-1) gene on K562 leukemia cell growth in vivo. METHODS: (1) The binding region of VEGF receptor (Flt-1) ligand was combined with fragment of IgH stable region to construct Flt-Ig fusion gene and insert into pcDNA3 vector. (2) By using electroporation, the pcDNA3/Flt-Ig was transfected into K562 leukemia cells, and selected by G418. Flt-Ig mRNA expression was detected by RT-PCR. (3) The transfected pcDNA3/Flt-Ig and pcDNA3-Ig K562 cells were respectively transplanted into nude mice and the tumor volume was dynamically measured. RESULTS: Five subclones of K562 cells with high expression of Flt-Ig gene have been established, one of them was transplanted into 6 nude mice. The tumor volume of experimental mice was obviously smaller than that of control mice, about one half of the control group (P < 0.05). CONCLUSION: The growth of transfected pcDNA3/Flt-Ig K562 cells was significantly inhibited. It is possible that soluble Flt-Ig protein secreted from K562/Flt-Ig cells neutralized VEGF produced from tumor cells, therefore inhibited the tumor angiogenesis.

Animals↗

PubMed2001

[Synthesis and release of pulmonary tissue adrenomedullin on hypoxic pulmonary hypertension in rats and its significance].

OBJECTIVE: To investigate the synthesis and release of adrenomedullin (AM) of lung tissue in rats on hypoxic pulmonary hypertension (HPH) and study its mechanism and significance in the pathogenesis process of HPH. METHODS: 54 Wistar rats were divided into hypoxia 10 d (n = 12), 20 d (n = 12), 30 d (n = 12) groups and control group (n = 18). The rats of hypoxia groups were exposed to chronic hypobaric hypoxia environment at high 5 km to establish HPH models. The expression of pulmonary cell AM protein, the content of plasma AM and bronchial alveolar lavage fluid (BALF) AM were determined by optical microscopy, immunohistochemistry and radio-immunoassay. RESULTS: AM was widely distributed in lung tissue. There was positive of AM in intraplasma of vascular endothelial cells (EC), vascular and bronchial smooth muscular cells (SMC), bronchial epithelial cells, macrophages (M phi) and type II alveolar epithelial cells in every groups. After hypoxia, the expression of AM in above cells, especially EC, SMC and M phi, increased more than control group. Plasma AM contents of hypoxia groups were higher than control group(P < 0.01). 20 d after hypoxia, the AM content was twice as control group. At 10 d to 20 d after hypoxia, BALF AM content was increased more than control group (P < 0.01). But at 30 d the content was decreased near to normal. CONCLUSIONS: Hypoxia is effective in promoting AM synthesis and release in pulmonary tissue and suggestes that AM as a peptide plays an important regulating role on pulmonary circulation, exchange of air and pulmonary vascular structural remodeling in the pathophysiological process of HPH.

Adrenomedullin↗

PubMed2001

[Pathological and virological studies of the liver tissues from the patients with sporadic hepatitis E].

OBJECTIVE: To study the pathological feature, viral distribution and replication in the liver tissue of sporadic hepatitis E(HE), and to explore the mechanism of the liver injury induced by hepatitis E virus(HEV). METHODS: The total bioptic liver tissues (n=54) were obtained from the patients with sporadic hepatitis E, including the clinical acute stage (n=20), the convalescent stage (n=16), and the chronic hepatitis B (CHB) overlapped with HEV infection recently (n=18). The pathological changes in the liver tissues were observed under the light and the electron microscope. HEV RNA was detected by in situ hybridization, and Kupffer cells were marked with immunohistochemistry. RESULTS: The HE liver tissues showed the pathological features in the clinical acute stage, presenting frequently with feathery degeneration of hepatocytes (100%), cholangiolar cholestasis (75.0%), and double nuclei and multinuclei hepatocytes (65.0%). The apoptotic body of hepatocyte was larger and irregular, and the proliferation of Kupffer cells was prominent. HEV RNA was distributed in hepatocyte cytoplasm near the nuclei. The positive rate of HEV RNA in acute stage was evidently higher than that in convalescent stage (100% vs 12.5%,P < 0.001), and the HEV RNA positive hepatocytes and the viral copies in acute stage were also more than in convalescent stage, in which the liver tissues were becoming normal. The liver tissue changes of the CBH overlapped with HEV infection were more severe compared with the single CHB. CONCLUSIONS: Sporadic HE had histopathological characteristics. HEV infection and replication in hepatocytes occurred mainly during clinical acute stage and regressed in convalescent stage, which suggested sporadic acute HE may have a good result. The immune-mediated liver injury by lymphocytes might be a main pathogenesis of HE,but the liver injury induced directly by HEV might not be excluded.

Adolescent↗

PubMed2001

[Molecular epidemiological characterization of rabies virus isolated from Guangxi].

BACKGROUND: To analyze the genotype of rabies virus isolated from different areas in Guangxi at different time. METHODS: mRNA of 8 Guangxi isolates, 1 Anhui isolates and 10 isolates from different countries of rabies virus were amplified by reverse transcription polymerse chain reaction (TR-PCR),and the products were sequenced. Phylogenetic analysis was carried out by phylip program. RESULTS: Phylogenetic analysis showed that 8 Guangxi isolates were related regionally, the homologic difference was lower than 2% among the isolates of the same area; higher than 15% among the isolates of two different areas.8 Guangxi isolates belonged to genotype A1, A2 a and A2 b; 10 chb of Guangxi isolates and thbkrb 2123 and thdg 2933 of Thailand isolates belonged to genotype A2 b, while Guangxi isolates were different from isolates of USA, Mexico and South Africa, which all belonging to genotype B. CONCLUSIONS: There are at least three groups of rabies virus based on limited sequencing of N gene in Guangxi.

Animals↗

PubMed2001

[Serological and pathological follow-up studies of the patients with single GBV-C/HGV RNA infection].

OBJECTIVE: To elucidate the pathogenicity of GBV-C/HGV in causing viral hepatitis. METHODS: The sera and bioptic liver tissues, which involved 8 cases of the second liver puncture with an interval of 2 years, from 24 cases of single GBV-C/HGV RNA positive patients were observed for more than 2 years. GBV-C/HGV RNA in the sera and liver tissues was detected by using RT-PCR and in situ hybridization, respectively. Under light and electron microscope, the pathology of the liver tissues was observed. RESULTS: At the beginning of the observation, the mean serum alanine transaminase(ALT) level was 60.17 IU/ml(range, 42.00-87.00 IU/ml), and the positive rates of anti-E2 antibody and GBV-C/HGV RNA in the sera and NS3 and/or NS5 in the liver tissues were 4.17%, 75.00% and 54.17%, respectively. In all the examined specimens, 79.17% of them showed mild acute or chronic hepatitis, mainly presenting with degeneration of hepatocytes, mild portal inflammation. GBV-C/HGV RNA and its NS3 and/or NS5 antigens were mainly detected in hepatocytes and a few mononuclear cells. In contrast, after more than 2 years, the natural change rate (negative rate of GBV-C/HGV) of 24 cases was 66.67% (P < 0.001). 75.00% had normal ALT level (P < 0.001) and 41.67% of anti-E2 antibody in the patients was positive (P < 0.001). Through histological observation, besides 2 cases of liver tissues showing very mild hydropic degeneration, there were no abnormal findings in 8 cases of the second liver biopsy. CONCLUSION: GBV-C/HGV could induce mild and self-limited hepatitis, which showed that GBV-C/HGV may be a light and self-limited pathogenic agent to human liver. E2 antibody appearance may indicate a recovery and provide a protection from GBV-C/HGV infection. Whether there is any other recovery marker in serum requires further study.

Adolescent↗

PubMed2001

[Immune response of mice to replication-defective recombinant adenovirus containing glycoprotein gene of rabies virus 3aG strain].

OBJECTIVE: To evaluate the immune response, of mice immunized with E1, E3 deleted replicative deficient recombinant adenovirus which can express glycoprotein of Chinese 3aG rabies virus. METHODS: Rapid fluorescent focus inhibition test (RFFIT) was used to determine the titer of neutralizing antibodies; specific antigen induced spleen lymphocyte proliferation was determined by in vitro 3H-TdR in-corporation assay, and lethal intracerebral challenge with CVS rabies virus was used to evaluate the protective effectiveness of the recombinant virus as candidate vaccine. RESULTS: Mice immunized by 1 x 10(7) recombinant virus developed high levels of rabies virus neutralizing antibodies (VNA). The spleen lymphocyte of the immunized mice also demonstrated remarkable increased proliferation after stimulation with inactivated rabies virus; 70%-90% of the mice immunized by the recombinant virus were protected from lethal intracerebral challenge with CVS rabies virus. CONCLUSION: E1, E3 deleted replication defective recombinant adenovirus containing 3aG glycoprotein gene may be developed as effective rabies vaccine to control rabies in China.

Animals↗

PubMed2001

[Study of blood dynamics of ophthalmic artery in patients with sudden sensorineural hearing loss using color Doppler flow imaging].

OBJECTIVE: To investigate the relationship between the pathogenesis of sudden sensorineural hearing loss (SSHL) and the disorder of blood circulation in inner ear. METHOD: Blood dynamics of the ophthalmic artery were studied quantitatively using color doppler imaging in 34 patients with SSHL. RESULT: Compared with 34 self-controls and 15 normal controls, 28 patients (82.4%) with SSHL had significantly lower blood flow velocities and higher resistance indices (P < 0.05), and there was no significant difference between the self-control group and the normal control group (P > 0.05). CONCLUSION: The study suggested that the blood situations--the decreased blood flow velocities and perfusion and increased resistance of ophthalmic artery in patients with SSHL maybe play a role in the pathogenesis of SSHL.

Adolescent↗

PubMed2001

[The curative effect of livostin spray on treating allergic rhinitis of children].

OBJECTIVE: To observe the effect of Livostin spray on children's allergic rhinitis and to search the mechanism of treating allergic rhinitis. METHOD: 113 patients were treated with Livostin spray (Livostin group) or normal saline spray (control group). RESULT: The total efficiency of Livostin group in treating allergic rhinitis is above 95.1% and that of the control group is 25.0%. Initial time of starting effect of Livostin (72.1%) is in 1 minute, and that of the control group (mostly 23.1%) is in 3 minutes. The keeping curative effect time of Livostin spray is mostly (72.1%) above 5 hours and that of the control group is mostly (30.8%) in 3 hours. After 2 weeks, the eosinophilic granulocyte number in nose's secretion of Livostin group is obviously reduced (P < 0.05). CONCLUSION: Livostin is better than control group in relieving symptoms, keeping curative effect and safety, so Livostin is one kind of effective drug in treating children's allergic rhinitis.

Administration, Intranasal↗

PubMed2001

[The effects of iron supplementation on auditory brain-stem response with iron deficiency anemia in rats].

OBJECTIVE: To evaluate the therapeutic methods of sensorineural hearing loss with iron deficiency anemia and their effects. METHOD: Sixty-eight Wistar rats were randomly divided into 3 groups: Group A (iron deficiency group A) 24 rats, group B (iron deficiency group B) 24 rats and group C (control group) 20 rats. Group A and B were fed with iron deficiency diet for 6 weeks. By analyzing ABR and DPOAE, hearing loss was detected in group A and B. Then, group A was given iron supplementation diet and hyperbaric oxygen therapies, and group B was given iron supplementation diet only. RESULT: The auditory thresholds and period latencies (PL) of I waves of ABR and DPOAE amplitude in 2 kHz and 3 kHz within group A and B were significantly different before and after treatment (P < 0.05). But the effects of treatment between these two groups had not significant differences (P > 0.05). CONCLUSION: It suggested that good results can be obtained by early iron supplementation in iron deficiency hearing loss cases. Hyperbaric Oxygen therapy may not be necessary.

Anemia, Iron-Deficiency↗

PubMed2001

Rapid analysis of momordicoside A in bitter melon by high performance liquid chromatography following solid phase extraction.

A rapid, simple and accurate method for the determination of momordicoside A has been established using solid phase extraction (SPE) followed by high performance liquid chromatography (HPLC). Sample was processed by SPE on a Carb cartridge (3 mL/250 mg), and was then determined by HPLC on a C18 column (4.6 mm i.d. x 250 mm, 5 microns) with V(acetonitrile):V(methanol):V(50 mmol/L potassium dihydrogen phosphate buffer) = 25:20:60 as mobile phase (0.8 mL/min) and UV detection at 208 nm. The calibration curves were linear from 10 mg/L to 1,000 mg/L (r2 = 0.9992). The analytical method was shown to be highly reproducible, giving all of the relative standard deviations and relative mean errors less than 10% for both intra-day and inter-day determinations. The absolute recoveries were greater than 90%.

Antineoplastic Agents, Phytogenic↗

PubMed2001

[Effects of blood transfusion on cellular immuno-function in patients with laryngeal carcinoma].

OBJECTIVE: To explore the influence of blood transfusion on cellular immunofunction in patient with laryngeal carcinoma. METHOD: EPICS-XL flow cytometry was used to measure T cell subgroup, NK cell and CD28 in 36 patients with laryngeal carcinoma pre-operation and 2 weeks post-operation. Patients were divided into allotransfusion group and non-transfusion group. Comparison was conducted between the 2 groups. RESULT: 1. Comparison with normal population, decreasing of CD3, CD4, NK cell and CD28 in the 36 patients pre-operation was statistically significant (P < 0.01). 2. Decreasing of CD3, CD4, NK cell and CD28 was statistically significant post-operation (P < 0.05). 3. In the non-transfusion group change of CD3, CD4, CD8, NK cell and CD28 post-operation was statistically insignificant (P > 0.05). CONCLUSION: While cellular immunofunction is generally low in patients with laryngeal carcinoma, allotransfusion will reduce further. It makes contribution to spreading and metastasis of carcinoma easier.

Aged↗