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Biomedical subjects

Hua Zhou

Publications and source records attributed to Hua Zhou.

At least 55 records · Page 3Linked to original sources

Quantification of sinomenine in caulis sinomenii collected from different growing regions and wholesale herbal markets by a modified HPLC method.

Caulis Sinomenii is the dried plant stems of Sinomenium acutum and Sinomenium acutum var. cinereum and has been used in Chinese medicine for treating rheumatic diseases for over a thousand years. Previous studies have demonstrated that sinomenine is a major active constituent in both plants and can be utilized as an indicator of quality of the medicinal herb Caulis Sinomenii. Currently, S. acutum and S. acutum var. cinereum are growing over a wide geographical range in China, with equally wide variations in growing conditions. The objectives of this research were to determine whether there were difference between the species and varieties, and whether the different growing conditions could result in different quality by determining the content of sinomenine in different samples. A modified HPLC method using a diode array detector (DAD) has been developed for efficiently quantifying sinomenine in the plants. Using this method, fourteen samples of S. acutum var. cinereum and eleven samples of S. acutum from growing regions as well as eighteen herbal samples of Caulis Sinomenii from wholesale herbal markets were evaluated. The results showed that there was no marked difference in the content of sinomenine between the species and varieties collected from growing regions; however, a very large variation was found among the samples collected from different regions. Moreover, the content of sinomenine in the plants of large size (stem diameter>3 cm) was much higher than those of small size (stem diameter<1 cm). This implies that the growing region has greater impact on the quality of Caulis Sinomenii in terms of the content of sinomenine than the species and varieties. The results also showed that the content of sinomenine in commercial Caulis Sinomenii was markedly lower than that in the plants collected directly from growing regions. This suggests that to obtain the herb with higher content of sinomenine and thus ensure greater efficacy, both in clinical applications and in pharmacological investigations, the plant of Caulis Sinomenii with controlled stem size collected directly from growing regions is preferable.

China↗

[Increased levels of advanced oxidation protein products are associated with atherosclerosis in chronic kidney disease].

OBJECTIVE: Accumulation of advanced oxidation protein products (AOPP) has been found in patients with chronic kidney disease (CKD). The study was performed to investigate the association between serum levels of AOPP and atherosclerosis in CKD. METHODS: 109 CKD patients were involved in this cross-sectional cohort study. Carotid artery intima-medial thickness (IMT), cross-sectional calculated intima-media area (cIM area) and plaques were determined with non-invasive high-resolution B-mode ultrasonography. Serum levels of AOPP, malonyldialdehyde (MDA), glutathione peroxidase (GSHPx) and C-reactive protein (CRP) were also determined. RESULTS: Higher serum AOPP levels were found in patients with CKD [(64.72 +/- 19.69) micromol/L] as compared with those in healthy controls [(30.16 +/- 6.46) micromol/L, P < 0.01]. AOPP levels in dialysis patients [(70.02 +/- 16.51) micromol/L] were significantly higher than those in pre-dialysis patients [(51.71 +/- 15.53) micromol/L, P < 0.01]. AOPP levels increased with the progression of renal dysfunction and inversely correlated with creatinine clearance (Ccr) (r = -0.292, P < 0.05). Patients with carotid artery plaques showed significantly higher levels of AOPP [(73.87 +/- 19.40) micromol/L] as compared with patients without carotid artery plaques [(58.41 +/- 16.09) micromol/L, P < 0.01]. Serum levels of AOPP were strongly associated with carotid artery IMT (r = 0.332, P < 0.01) and cIM area (r = 0.288, P < 0.05). By stepwise multiple regression analysis and adjusting for age, gender, blood pressure, smoking, diabetes, body mass index (BMI), hemoglobin, lipid and albumin, strong association was still present between AOPP levels and carotid artery IMT (beta = 0.313, P < 0.001) and cIMarea (beta = 0.301, P < 0.01). Serum levels of AOPP were correlated positively with serum MDA (r = 0.300, P = 0.01) and CRP levels (r = 0.255, P < 0.05), while negatively with serum GSHPx (r = -0.647, P < 0.01). CONCLUSIONS: Serum levels of AOPP increased with the progression of renal failure and closely associated with occurrence of atherosclerosis. Strong association between serum AOPP and CRP suggests that AOPP might be involved in the pathogenesis of micro-inflammation which has been considered as a contributing factor for atherosclerosis in CKD.

Adult↗

[An exploratory study on in vitro effects and mechanism of leflunomide on dendritic cells of systemic lupus erythematosus].

OBJECTIVE: To detect the effects of leflunomide to phenotype and function of dendritic cells (DCs) in systemic lupus erythematosus (SLE) patients, reveal the effective mechanism inducing remission of SLE and lay a research foundation for using 'inhibit' DCs to treat SLE in future. METHODS: The monocytes were isolated from peripheral blood of SLE patients and cultivated into DCs with cytokines such as GM-CSF and IL-4. A771726 (active metabolite) was added in with cytokines in leflunomide group, but not in control. DCs were harvested after 9 days culture. CD(80), CD(83), CD(86) and HLA-DR surface markers on DCs were detected by flow cytometry (FACS). The ability of DCs stimulating lymphocytes proliferation was detected by MTT assay. IL-10 and IFNgamma level in the supernatant of MLR were detected by ELISA and T cell subtype after MLR was detected by FACS. RESULTS: The DCs treated with A771726 showed a lower percentage expression of CD(83), CD(86) and HLA-DR phenotype (CD(83): 72.70 +/- 1.77 vs. 79.36 +/- 4.80, CD(86): 63.50 +/- 14.06 vs. 83.91 +/- 9.81, HLA-DR: 80.44 +/- 12.56 vs. 90.51 +/- 8.63, all P < 0.01), a weaker ability to stimulating T lymphocytes proliferation (at DC:TC = 1:10, 0.285 +/- 0.079 vs. 0.458 +/- 0.100; at DC:TC = 1:50, 0.194 +/- 0.054 vs. 0.382 +/- 0.023, all P < 0.01) and a lower secretive level of IL-10 in the MLR supernatant [(195.0 +/- 36.9) microg/L vs. (423.6 +/- 93.2) microg/L, P < 0.01], exclude those it could still increase amount of a new T cell subtype--CD(4)(+)CD(25)(+)CTLA(4)(+) T cell (12.00% & 6.23%). CONCLUSIONS: A771726 can inhibit DCs maturation, the immature DCs can inhibit T cells proliferation and refrain T cells from dividing into Th(2) subtype, and also the immature DCs can induce a sort of regulate T cell (CD(4)(+)CD(25)(+)CTLA(4)(+) T cell) production. Through that LEF may correct part over humor immune dysfunction and get a new immune balance in SLE.

Adolescent↗

Transient myofibroblast differentiation of interstitial fibroblastic cells relevant to tubular dilatation in uranyl acetate-induced acute renal failure in rats.

To investigate the mechanisms of myofibroblast differentiation of interstitial fibroblastic cells (FCs) in rats with uranyl acetate-induced acute renal failure (ARF), we examined the relationship between the expression of alpha-smooth muscle actin (alpha-SMA), myofibroblast phenotype and tubular dilatation as well as cell shape and adhesion of FCs. Peritubular alpha-SMA-positive myofibroblasts appeared after induction of ARF and extended along the damaged, dilated proximal tubules and then almost disappeared after proximal tubular recovery. The perimeter of proximal tubules correlated with fractional areas stained for alpha-SMA (P<0.001). Most alpha-SMA-positive cells did not incorporate [3H]-thymidine, indicating a low proliferative activity. Transmission electron microscopy showed that FCs increasingly attached to the tubular basement membrane by elongated cytoplasm-containing microfilament bundles, which formed abundant adherens and gap junctions from day 4 to day 7. Scanning electron microscopy showed hypertrophic FCs covering large areas of tubules after induction of ARF. Administration of chlorpromazine, which can inhibit cytoskeletal movement, after induction of ARF partially inhibited myofibroblast differentiation of FCs immunohistochemically and morphologically and resulted in more dilated proximal tubules in concert with aggravation of renal dysfunction and inhibition of regenerative repair at day 4 than vehicle-administered rats. Our results indicate that mechanical tension, judged by tubular dilatation, may contribute to the induction of alpha-SMA phenotype with increased stress fiber formation and intercellular junctions in FCs to support damaged nephron structures by adjusting tensional homeostasis in rats with uranyl acetate-induced ARF.

Actins↗

Integrin engagement differentially modulates epithelial cell motility by RhoA/ROCK and PAK1.

Integrin-ligand binding regulates tumor cell motility and invasion. Cell migration also involves the Rho GTPases that control the interplay between adhesion receptors and the cytoskeleton. We evaluated how specific extracellular matrix ligands modulate Rho GTPases and control motility of human squamous cell carcinoma cells. On laminin-5 substrates, the epithelial cells rapidly spread and migrated, but on type I collagen the cells spread slowly and showed reduced motility. We found that RhoA activity was suppressed in cells attached to laminin-5 through the alpha3 integrin receptor. In contrast, RhoA was strongly activated in cells bound to type I collagen and this was mediated by the alpha2 integrin. Inhibiting the RhoA pathway by expression of a dominant-negative RhoA mutant or by directly inhibiting ROCK, reduced focal adhesion formation and enhanced cell migration on type I collagen. Cdc42 and Rac and their downstream target PAK1 were activated following adhesion to laminin-5. PAK1 activation induced by laminin-5 was suppressed by expression of a dominant-negative Cdc42. Moreover, constitutively active PAK1 stimulated migration on collagen I substrates. Our results indicate that in squamous epithelial cells, collagen-alpha2beta1 integrin binding activates RhoA, slowing cell locomotion, whereas laminin-5-alpha3beta1 integrin interaction inhibits RhoA and activates PAK1, stimulating cell migration. The data demonstrate that specific ligand-integrin pairs regulate cell motility differentially by selectively modulating activities of Rho GTPases and their effectors.

Adenoviridae↗

The induction of cell cycle regulatory and DNA repair proteins in cisplatin-induced acute renal failure.

The purpose of this study was to evaluate the expressions and the roles of proteins involved in cell cycle regulation and DNA repair in cis-diamminedichloroplatinum (II) (cisplatin or CDDP)-induced acute renal failure (ARF). Treatment with CDDP (6 mg/kg, iv) induced tubular damage and increased serum creatinine (Scr) and the number of TUNEL-positive cells in the outer stripe of the outer medulla in rats, which reached peak levels at 5 days after CDDP. The expressions of cyclin-dependent kinase inhibitors (p21 and p27), cyclin B1, cyclin D1, PCNA, GADD 45, and GADD 153 were significantly increased in the outer medulla, reaching peak levels at 3 days after CDDP. Increments of p27 and PCNA were observed in the same nuclei. Sodium arsenite (SA), a heavy metal, attenuated tubular damage and increased Scr- and TUNEL-positive cells at 5 days after CDDP. SA augmented CDDP-induced increment of p27 but suppressed the increased expression of cyclin B1 and cyclin D1 at 3 days after CDDP. SA-induced attenuation of nephrotoxicity was associated with enhanced expression of proliferating cell nuclear antigen (PCNA) and growth-arrest and DNA damage (GADD) 153 in damaged tubular cells. Our findings indicated that (1) proteins related to cell cycle regulation and DNA repair are induced in CDDP nephrotoxicity, (2) the SA-induced attenuation of CDDP nephrotoxicity is associated with increased expression of p27 and decreased expression of cyclin B1 and cyclin D1, they all induce cell cycle arrest at G1/S and G2/M, and (3) enhanced expression of DNA repair-related proteins is also associated with attenuation of CDDP-nephrotoxicity.

Acute Kidney Injury↗

[Tutin-induced epileptiform discharge of CA1 pyramidal cells in rat hippocampal slices].

Previous studies showed that a mixture, Coriaria Lactone (CL), extracted from a traditional Chinese herb Loranthus Parasiticus Mer, had a great excitatory influence on the nervous system, resulting in seizure. But what component in CL causes seizure is unclear. Tutin is a pure chemical component derived from CL. The present experiments were carried out to test if tutin has any epileptogenic action and to preliminarily study the mechanism underlying that action in vitro. The electrical activity of CA1 pyramidal cells, population spikes (PS), evoked by stimulation of the Schaffer collaterals in rat hippocampal slices was recorded extracellularly. The effects of tutin on the PS and the antagonistic actions of CNQX and AP-5 on the tutin-induced effects were investigated. The results are as follows. (1) Superfusion with 40, 30 and 20 microg/ml tutin caused significant increase in the amplitude and number of PS waves evoked by stimulating the Schaffer collaterals. Thirty minutes after superfusion of tutin, the amplitude of the first wave of the PSs was increased by (388.7+/-0.1)%, (317.2+/-19.1)% and (180.9+/-11.6)% in each of the above three groups, respectively, compared with the control (for each group, n=5, P<0.05). (2) With increase in amplitude, the PS number was increased to 4~11 waves from a single wave in the control and manifested multiple epileptiform discharges 30 min superfusion with tutin. (3) Spontaneous epileptiform discharges of CA1 pyramidal cells were obtained in 9 out of 34 cases after tutin superfusion. (4) The tutin-induced multiple epileptiform discharges of the CA1 pyramidal cells were completely blocked by CNQX, in aspects of both amplitude and number of the PS. Following the application of AP-5, the increase in the wave number of the tutin-induced epileptiform discharges was inhibited but the increase in the amplitude of the discharges was not significantly affected. These results indicate that tutin can induce typical multiple epileptiform discharges of CA1 pyramidal cells in rat hippocampal slices and might be used as an efficient epileptogenic agent, and that the excitable glutamate receptors, especially the non-NMDA receptors, may participate in the genesis of tutin-induced epileptiform discharges.

Animals↗

CFD evaluation of drop retraction methods for the measurement of interfacial tension of surfactant-laden drops.

Drop retraction methods are popular means of measuring the interfacial tension between immiscible polymers. Experiments show that two different drop retraction methods, imbedded fiber retraction (IFR) and deformed drop retraction (DDR), give inconsistent results when a surfactant is present on the surface of the drop. These inconsistencies are deemed to be due to dilution of the surfactant and due to gradients in interfacial concentration of surfactant along the drop surface. This physical picture is quantified for the simple case of a Newtonian drop in a Newtonian matrix, with an insoluble, nondiffusive surfactant at the interface. The drop is deformed in computational fluid dynamics simulations by shearing the matrix, and then allowed to retract. Dilution and interfacial tension gradients effects are found to be especially large at the early stages of retraction, making IFR unsuitable for measuring the interfacial tension of surfactant-laden interfaces. The effects of surfactant dilution and gradients are found to persist even at late stages of retraction, causing the DDR method to underestimate the equilibrium interfacial tension significantly. The largest underestimates occur when the drop viscosity is lower than the matrix viscosity.

Journal Article↗

Insulin-like growth factor-I increases p21 expression and attenuates cisplatin-induced acute renal injury in rats.

BACKGROUND: Exogenous insulin-like growth factor-I (IGF-I) promotes recovery from ischemic renal injury, but its effect on cisplatin (CDDP)-induced nephrotoxicity and its mechanisms for the attenuation of renal injury are unknown. METHODS: We administered recombinant human IGF-I (rhIGF-I, 150 micro g/day, i.p.) once a day 24 h prior to and after CDDP (5 mg/kg, i.v.) injection in rats. RESULTS: The rhIGF-I treatment significantly decreased serum creatinine (0.92 +/- 0.11 vs 1.50 +/- 0.15 mg/dl; P < 0.05), the tubular damage score, and the ratio of apoptotic cells to tubular epithelial cells in the outer stripe of the outer medulla on day 5 ( P < 0.05). rhIGF-I significantly increased the numbers of p21-positive nuclei (5.15 +/- 0.19 vs 3.45 +/- 0.42/x400 high-power field (HPF); P < 0.05) and proliferating cell nuclear antigen (PCNA)-positive nuclei (28.61 +/- 1.89 vs 18.26 +/- 2.14/x400 HPF; P < 0.05), but decreased the number of cyclin D1-positive cells (3.3 +/- 0.3 vs 6.3 +/- 1.7/x400 HPF; P < 0.05) on day 3. rhIGF-I did not alter 5-bromo-3-deoxyuridine (BrdU) incorporation. CONCLUSIONS: Our findings suggested that rhIGF-I increased renal p21 and PCNA expression, but reduced cyclin D1 expression in CDDP-treated kidneys. Exogenous rhIGF-I may ameliorate renal damage, in part by stopping the cell cycle at G1/S phase. Exogenous insulin-like growth factor-I (IGF-I) promotes recovery from ischemic renal injury, but its effect on cisplatin (CDDP)-induced nephrotoxicity and its mechanisms for the attenuation of renal injury are unknown.

Acute Kidney Injury↗

Macrophage inhibitor, semapimod, reduces tumor necrosis factor-alpha in myocardium in a rat model of ischemic heart failure.

Pharmaceutical agents aimed at reducing tumor necrosis factor-alpha (TNF-alpha) levels appeared to be attractive possibilities in the medical management of heart failure, as heart failure was shown to be associated with high TNF-alpha levels. However, therapies specifically targeting TNF-alpha failed to show any survival benefit. We examined whether a broad inhibition of inflammatory cytokine production secondary to macrophage inhibition would be more effective at improving cardiac function in the setting of heart failure. To this end, we studied Semapimod (formerly known as CNI-1493), a synthetic guanylhydrazone that inhibits macrophage activation and the production of several inflammatory cytokines. Left anterior descending coronary ligation surgery was performed on each animal to induce a myocardial infarction. After confirming heart failure by echocardiography, the animals were randomly assigned to one of four groups: (1) rats with myocardial infarct receiving high-dose Semapimod, 10 mg/kg/d (MI-H, N = 13); (2) rats with myocardial infarct receiving low-dose Semapimod, 3 mg/kg/d (MI-L, N = 9); (3) rats with myocardial infarct receiving vehicle treatment, 2.5% mannitol in water (MI-0, N = 9); and (4) control rats with sham operation and vehicle treatment (Sham, N = 10). Both Semapimod and vehicle treatments were administered by daily tail vein injections over a course of five days. Echoes were repeated at 2, 5, and 9 weeks following treatment. At 9 weeks, hemodynamic data were collected and the animals were euthanized. Trichrome staining was done to assess infarct, and immunohistochemistry was performed to assess TNF-alpha levels. Prior to drug administration, serum was taken from 5 random rats. No detectable level of TNF-alpha was seen (lower limit of detection for the assay used = 12.5 pg/mL). Also prior to any treatment, echocardiography confirmed significant cardiac impairment of rats undergoing LAD ligation as compared with sham. Over the course of the 9 weeks, there were 4 deaths, all in the MI-H group. There was no difference between Semapimod-treated animals and vehicle-treated MI animals in any echocardiographic or hemodynamic parameter. TNF-alpha staining in the noninfarcted region was evident only in the MI groups, not the sham group. When blindly compared on a semiquantitative scale (ie, 0 = no visible staining to 3 = marked staining), a significant difference in staining was observed between MI-0 versus MI-H (1.19 +/- 0.32 versus 0.33 +/- 0.14; P = 0.03) and between MI-0 and MI-L (1.19 +/- 0.32 versus 0.39 +/- 0.22; P = 0.05). In this setting, despite the fact that Semapimod treatment decreased tissue TNF-alpha levels, it did not improve cardiac function, and at high doses it was associated with higher mortality. These results in a rodent model confirm the results of clinical trials with etanercept and infliximab (ie, that decreasing TNF levels in plasma or tissues does not improve cardiac function and may actually increase mortality).

Animals↗

[Analyses of ultrasonographs of adrenal gland cysts in comparison with pathological findings].

OBJECTIVE: To investigate the value of ultrasonography in the diagnosis of adrenal gland cysts. METHODS: Six patients with adrenal gland cysts were examined by two-dimensional ultrasonography and color Doppler flow imaging (CDFI), and the results were compared with the pathological findings. RESULTS: The diagnoses by ultrasonography and CDFI were consistent with the pathological findings in 5 cases. CONCLUSION: Ultrasonography and CDFI can be an accurate diagnostic modality for adrenal gland cysts.

Adrenal Gland Diseases↗

[Hyperhomocysteinemia, oxidative stress and microinflammation in chronic renal failure: their roles in atherogene].

OBJECTIVE: To investigate the relationship between hyperhomocysteinemia, oxidative stress and microinflammation in patients with chronic renal failure (CRF), and its role in the pathogenesis of atherosclerosis seen in these patients. METHODS: One hundred and fourteen CRF patients and 37 healthy volunteers were involved in the study. The levels of plasma total homocysteine (tHcy) were determined by fluorescence polarization immunoassay. Plasma malondialdehyde (MDA) levels were analyzed by thiobarbituric acid reaction. The activity of glutathione peroxidase (GSHPx) in plasma was measured by spectrophotometry. Serum C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)alpha were determined by ELISA. Intima-medial thickness (IMT) of extracranial common carotid artery and the presence of atherosclerotic plaques was determined by using noninvasive high-resolution B-mode ultrasonography. RESULTS: Levels of tHcy, MDA, CRP and TNFalpha in the non-dialysis CRF patients were significantly higher than those in the healthy controls and increased with the progression of renal insufficiency, while plasma activity of GSHPx decreased progressively with decline of renal function. Compared with the pre-dialysis patients, hemodialysis patients exhibited higher levels of tHcy, MDA, CRP, IL-6 and TNFalpha, and lower levels of GSHPx activity. There were no significant difference in the levels of tHcy, MDA, CRP, IL-6, TNFalpha, and GSHPx activity between patients dialyzed with hemophan, polysulfone and cellulose triacetate membrane. Prevalence of atherosclerotic plaque and increased IMT in carotid artery were significantly higher in CRF patients compared with the age-matched controls and associated with the levels of tHcy, MDA and CRP. Multivariate stepwise regressive analysis showed that increased IMT in CRF patients was closely related to the levels of tHcy, MDA, CRP, blood glucose, and very low density lipoproteins (R(2) = 0.572, P < 0.001). The factors associated with plasma MDA (representing lipid peroxidation level) were GSHPx activity (standard regressive coefficient, beta = -0.651, P < 0.01), tHcy level (beta = 0.229, P < 0.01), and serum creatinine (beta = 0.163, P < 0.05). The factors associated with serum CRP (representing microinflammation state) were IL-6 (beta = 0.532, P < 0.01), TNFalpha (beta = 0.212, P < 0.01), MDA (beta = 0.209, P < 0.05), and plasma albumin (beta = -0.297, P < 0.05). CONCLUSION: Hyperhomocysteinemia in CRF patients may accelerate oxidative stress, and lipid peroxidation may be involved in the occurrence of microinflammation state. The complex interaction between hyperhomocysteinemia, oxidative stress and microinflammation may result in accelerated atherosclerosis seen in CRF.

Adult↗

[The control study on risk factors of high-risk population in diabetes].

OBJECTIVE: To examine the significance of individual risk on diabetes to subjects who underwent diabetes screening. METHODS: 2003 asymptomatic diabetes subjects with high-risk factors of diabetes as family history, obesity, hypertension, and/or dyslipidemia, fetal giant history were screened. 5362 subjects having no risk factors but from the same community were allocated as controls. RESULTS: There were 131 (6.54%) diabetes identified in the screening group and 1547 (77.23%) subjects having 1 risk factor, 387 (19.27%) having 2 risk factors, 70 (3.49%) having 3 or more risk factors. There were 96 (1.79%) diabetes identified in the control group. Compared with control group, the OR (95% CI) value was 2.68 (2.20-3.25) after adjusted on age among the high risk group. The OR value of those having 1 risk factor was 2.89, but these having 3 or more risk factors increased to 4.68. CONCLUSION: The relation between the risk of high-risk group with diabetes and the number of risk factors of diabetes presented positive correlation. Early and regular screening for diabetes was essential in these individuals with high-risk factors.

Adult↗

[Diagnosis and treatment on osteoradionecrosis of skull base after radiotherapy for nasopharyngeal carcinoma].

OBJECTIVE: To investigate the diagnosis and management on osteoradionecrosis (ORN) of skull base in the patients with nasopharyngeal carcinoma (NPC) after radiotherapy. METHODS: All patients (n = 15) diagnosed as NPC and ORN of skull base were studied on the clinical data, diagnosis and therapy. RESULTS: All the patients were found with foul odor, headache, bleeding and exposed necrotic bone. 9 patients were treated by surgery, among them 2 patients died of temporal lobe radionecrosis, and the survival time of remaining 7 patients was 2 to 7 years. 5 patients with extensive ORN and 1 patient with local ORN were treated by conservative methods, among them 3 died of nasopharyngeal bleeding and 1 died of respiratory and heart failure, survival time of the remaining 2 patients was 3 to 5 years. CONCLUSIONS: ORN can be diagnosed by clinical characteristics, CT or MR, and endoscopic findings. Surgery is the best choice for ORN. The patients with extensive ORN or radiation-induced cranial neuropathy had poor prognosis. The most common causes of death were nasopharyngeal bleeding and exhaustion.

Adult↗