[Expression and significance of INSM1 and SOX11 in pancreatic neuroendocrine tumor and solid pseudopapillary neoplasm].

OBJECTIVE: To investigate the expression and significance of insulinoma associated protein 1 (INSM1) and SRY-related high-mobility group box 11 (SOX11) in pancreatic neuroendocrine tumor (PNET) and solid pseudopapillary neoplasm (SPN). METHODS: To detect the expression of INSM1, SOX11, Syn, CgA, CD56, ß-catenin, and CD99 in 56 cases of PNET, 42 cases of SPN, 16 cases of ductal adenocarcinoma (DACC) and 8 cases of acinar cell carcinoma (ACC) by immunohistochemistry. The application value of combination of INSM1 and SOX11 was compared with conventional markers (Syn, CgA, CD56, ß-catenin, and CD99) in diagnosis and differential diagnosis of PNET and SPN. RESULTS: (1) In the 56 cases of PNET, the positive signals of INSM1 were located in the tumor and islet nucleus, the positive expression rate in the tumor tissues was 91.07% (51/56), whereas the signal was absent in 42 cases of SPN, 16 cases of DACC and 8 cases of ACC, and there were significant statistical difference between PNET with SPN, DACC, and ACC respectively (P < 0.001). (2) The positive signals of SOX11 were located in the tumor nucleus, with the positive expression rate was 92.86% (39/42) in SPN, however, the positive expression rate of SOX11 was 8.93% (5/56) in PNET, which included 3 cases of G1 and 2 cases of G3 types of PNET, the SOX11 positive signal was absent in 16 cases of DACC, 8 cases of ACC and peritumoral nomal pancreatic tissue, and the differences were statistically significant of positive rate between SPN with PNET, DACC and ACC, respectively (P < 0.001). (3) The sensitivity of INSM1(+)/SOX11(-) immunophenotype for PNET was 85.71%, vs. CD56 (57.14%), the difference was statistically significant (P=0.001); vs. Syn (80.36%) and CgA (71.43%), the difference was no statistically significant (P>0.05). The specificity of INSM1(+)/SOX11(-) for PNET was 100.00%, vs. Syn (42.86%) and CD56 (47.62%), the difference was statistically significant (P < 0.001); vs. CgA (92.86%), the difference was no statistically significant (P>0.05). The sensitivity of INSM1(-)/SOX11(+) immunophenotype for SPN was 92.86%, vs. ß-catenin (90.48%) and CD99 (85.71%), the difference was no statistically significant (P>0.05). The specificity of INSM1(-)/SOX11(+) for SPN was 96.43%, vs. CD99 (48.21%), the difference was statistically significant (P < 0.001); vs. ß-catenin (100.00%), the difference was no statistically significant (P>0.05). (4) The positive expression of INSM1 and SOX11 in PNET and SOX11 were not correlated with clinicopathological parameters (age, gender, tumor size, location, grade, and metastasis) (P>0.05). CONCLUSION: The positive expression patterns of INSM1 and SOX11 in PNET and SPN respectively are conductive to distinguish the both tumors. The combination of both take precedence over some corresponding conventional immunohistochemical markers in terms of sensitivity and specificity.

[Expression of CD200 and INSM1 in gastrointestinal and pancreatic neuroendocrine neoplasms and its diagnostic values].

Objective: To investigate the expression and diagnostic values of CD200 and insulinoma associated protein 1 (INSM1) in gastrointestinal and pancreatic neuroendocrine neoplasm (GIP-NEN). Methods: The expression of CD200, INSM1, Syn and CgA was detected in 69 cases of GIP-NEN, 66 cases of gastrointestinal and pancreatic non-neuroendocrine neoplasm (GIP-nonNEN) and 16 cases of metastatic neuroendocrine neoplasm by immunohistochemistry, to compare the values of CD200, INSM1, Syn, CgA and their combinations in diagnosing GIP-NEN. Receiver operating characteristics (ROC) curve was used. Results: The immunoreactivity of CD200 was present in the cytoplasma and/or membrane of the neoplasms cells, the positive expression rates in GIP-NEN and GIP-nonNEN were significantly different (P<0.01). The sensitivity and specificity of CD200 for diagnosing GIP-NEN were 95.7% and 78.8%, respectively. There was significant difference of the positive rates of CD200 between neuroendocrine tumor and neuroendocrine carcinoma (P=0.05). The immunoreactivity of INSM1 was present in the nuclei of neoplasms cells. The positive expression rates in GIP-NEN and GIP-nonNEN were significantly different (P<0.01). The sensitivity and specificity of INSM1 for diagnosis of GIP-NEN were 85.5% and 95.5%, respectively. There were also significantly different positive rates of INSM1 between neuroendocrine tumor and neuroendocrine carcinoma, as well as between G1 and G3 neuroendocrine tumors (P<0.05). There was no difference in the area under ROC curve (AUC) of single stain of CD200, INSM1, Syn or CgA (0.857, 0.907, 0.890 and 0.833, respectively, P>0.05). The sensitivity of combined CD200+INSM1 stains for diagnosing GIP-NEN was significantly higher than that of Syn+CgA (85.5% vs. 63.8%, P<0.05). The AUC of two combinations were 0.962 and 0.925, respectively, which were not statistically different (P>0.05). Conclusions: CD200 and INSM1 are two novel markers of neuroendocrine neoplasm, which aid to diagnosis for GIP-NEN and exclude its mimickers. They are associated with tumor grades. Combining both as an immunohistochemical panel shows high sensitivity and specificity. Thus, the combined panel can be utilized as useful supplement for Syn and CgA.

[Effect of renal function on sarcopenia in elderly male patients with chronic kidney disease].

Objective: To evaluate the effect of renal function on sarcopenia in elderly male patients with chronic kidney disease (CKD). Methods: A total of 105 male CKD patients aged ≥65 years who were admitted to the Chinese PLA General Hospital between October 1, 2018 and January 30, 2019 were included in this study. Using two different equations to estimate glomerular filtration rate (GFR), respectively. According to the sarcopenia criteria, the participants were categorized as the non-sarcopenia group (n=72) and the sarcopenia group (n=33), respectively. The association of estimated GFR (eGFR) and the sarcopenia in the male CKD patients was analyzed using the model of multivariate logistic regression. Results: Among the 105 patients, the median age was 74 (68, 77) years old. The prevalence of sarcopenia was 31.4% (33/105). According to the multivariate logistic regression analysis, eGFR based on serum creatinine and Cys-C (eGFRscr-cys) lower than 45 ml·min(-1)·(1.73 m(2))(-1) (OR=4.17, 95%CI:1.08-16.02, P=0.038) and eGFR based on Cys-C (eGFRcys) lower than 45 ml·min(-1)·(1.73 m(2))(-1) (OR=3.99, 95%CI:1.08-14.75, P=0.038) were independent risk factors for underlying sarcopenic, respectively. The area under the receiver operating characteristics curve (AUC) revealed that eGFRscr-cys (AUC=0.67) was more suitable than eGFRcys (AUC=0.64) to predict the sarcopenia in elderly male patients with CKD. Conclusion: The increased incidence of sarcopenia in elderly men with CKD is accompanied with deterioration of renal function.

[Related factors of frailty in the elderly male patients with chronic kidney disease].

Objective: To investigate the characteristics of frailty in the elderly male patients with chronic kidney disease (CKD) and the effects of renal function on the incidence of frailty. Methods: A total of 105 non-dialysis CKD patients aged ≥65 years who were admitted to the Chinese PLA General Hospital between October 1, 2018 and January 30, 2019 were included in this study. Their clinical data and laboratory indicators were collected. Frailty was defined according to Fried frailty criteria. According to the frailty scores, the participants were categorized as non-frail (n=37), intermediately frail (n=37) and frail (n=31). The association of frailty and the level of estimated glomerular filtration rate (eGFR) in the patients was analyzed using the model of multivariate Logistic regression. Results: Among the 105 patients, the mean age was 74 (68, 77) years old. The incidence of frail and intermediate frail was 35.2% (37/105) and 29.5% (31/105), respectively. Multivariate logistic analysis showed statistically significant associations of frailty with age (OR=1.14, 95%CI:1.08-1.20, P<0.001), body mass index (OR=0.87, 95%CI:0.79-0.95, P=0.001) and the level of eGFR (OR=0.98, 95%CI:0.96-0.99, P=0.003) in those patients. The incidence of frail in patients with eGFR<45 ml·min(-1)·(1.73 m(2))(-1) and 45-59 ml·min(-1)·(1.73 m(2))(-1) was 1.02 (OR=2.02, 95%CI: 1.06~3.87) and 0.84 (OR=1.84, 95%CI: 1.05-3.22) times higher than that of eGFR≥60 ml·min(-1)·(1.73 m(2))(-1), respectively. Conclusion: The incidence of frailty in the elderly patients with CKD is affected by many factors, such as age, body mass index and renal function, and increases with decreased renal function.

Genetic and morphology analysis among the pentaploid F1 hybrid fishes (Schizothorax wangchiachii ♀ × Percocypris pingi ♂) and their parents.

Triploid and pentaploid breeding is of great importance in agricultural production, but it is not always easy to obtain double ploidy parents. However, in fishes, chromosome ploidy is diversiform, which may provide natural parental resources for triploid and pentaploid breeding. Both tetraploid and hexaploid exist in Schizothorax fishes, which were thought to belong to different subfamilies with tetraploid Percocypris fishes in morphology, but they are sister genera in molecule. Fortunately, the pentaploid hybrid fishes have been successfully obtained by hybridization of Schizothorax wangchiachii (♀, 2n = 6X = 148) × Percocypris pingi (♂, 2n = 4X = 98). To understand the genetic and morphological difference among the hybrid fishes and their parents, four methods were used in this study: morphology, karyotype, red blood cell (RBC) DNA content determination and inter-simple sequence repeat (ISSR). In morphology, the hybrid fishes were steady, and between their parents with no obvious preference. The chromosome numbers of P. pingi have been reported as 2n = 4X = 98. In this study, the karyotype of S. wangchiachii was 2n = 6X = 148 = 36m + 34sm + 12st + 66t, while that the hybrid fishes was 2n = 5X = 123 = 39m + 28sm + 5st + 51t. Similarly, the RBC DNA content of the hybrid fishes was intermediate among their parents. In ISSR, the within-group genetic diversity of hybrid fishes was higher than that of their parents. Moreover, the genetic distance of hybrid fishes between P. pingi and S.wangchiachii was closely related to that of their parental ploidy, suggesting that parental genetic material stably coexisted in the hybrid fishes. This is the first report to show a stable pentaploid F1 hybrids produced by hybridization of a hexaploid and a tetraploid in aquaculture.

[The stimulation of human pulmonary artery endothelial cells by cigarette smoke extract contributed to cell senescence and induced human pulmonary artery smooth cell migration].

Objective: To observe the senescent effect of human pulmonary arterial endothelial cells (HPAEC) stimulated by cigarette smoke extract (CSE) and the effect of secretion of senescent cells on human pulmonary arterial smooth muscles cell (HPASMC) proliferation and migration. Methods: HPAEC was treated with different concentrations of CSE in vitro and cell proliferation was determined by CCK8, senescence cells analyzed by detecting the ß-gal activity, and the senescent proteins of cells measured by Western blot. The concentration of senescence-associated secretory phenotype (SASP) was detected by ELISA and the expression of MCP-1 and TGF-ß1 was measured by Real-time PCR. The number of the proliferated cells was measured by Transwell assay and immunoflurescence. Results: The HPAEC was aging with the stimulation concentration of CSE increasing and the stimulation time prolonging (P<0.05). Western blot indicated that the senescent associated protein p53 or p21 increased markedly after 48 h and 72 h CSE-exposure (n=3, P<0.05). The SA-ß-Gal staining showed that the number of senescent cells increased as the exposure time prolonged. Compared with the control group, cell viability of 48 h group(1.8±0.1) and 72 h group (1.8±0.1) decreased significantly. The flow cytometry showed a significant difference between the CSE group(14.1±1.2) and the control group(28.5±1.8) in S phase(P<0.01), indicating cell cycle arrest. The SASP was increasing as the CSE-exposure prolonged. Compared with the control group(177±39), the 48 h group(460±43) and the 72 h group(609±64) showed a marked increase in MCP-1(P<0.05). For TGF-ß1, it had a same tendency and a significant difference between the control group(121±18) and the 48 h group(413±32) or 72 h group(606±67, both P<0.05). In the meantime, the bFGF increased after 48 h stimulation(291±13, P<0.05). Besides MCP-1, TGF-ß1 showed a significant difference between the control group and the 72 h CSE-exposure group (P<0.01). Premature cells could secrete SASP which induced HPASMC proliferation. After different times of conditioned medium stimulation, HPASMC proliferated especially at 72 h(P<0.05) . The immnoflorescence and Transwell assay confirmed this finding. Conclusion: CSE could induce senescence of HPAEC and SASP production which improved HPASMC proliferation and migration.

[Analysis of risk factors and prognosis for bleeding in very old male patients with stage 5 chronic kidney disease].

Objective: To analyze the risk factors and prognosis of bleeding in very old male patients with stage 5 chronic kidney disease (CKD). Methods: The clinical data of 143 very old male patients with stage 5 CKD was retrospectively analyzed. According to the occurrence of bleeding, the patients were divided into two groups including the hemorrhage group and the non-hemorrhage group. The history of diseases, renal function, blood cell parameters and coagulation index were compared and analyzed between the two groups. The prognosis of patients with a period of 12 months was studied. Results: Among 143 patients, 67 cases (46.85%) suffered bleeding, and the other 76 patients (53.15%) were without bleeding. The age[(89±4) vs (87±5) years, P=0.02], pulmonary infection (32.84% vs 9.21%, P<0.001), activated partial thromboplastin time[(40.86±8.02) vs (38.41±5.72) s, P=0.036], fibrinogen[(4.09±0.75) vs (3.62±0.67) g/L, P<0.001], blood urea nitrogen (BUN)[(37.19±10.66) vs (32.86±8.97)mmol/L, P=0.009]were significantly increased in the hemorrhage group compared with the non-hemorrhage group. Multivariate logistic regression analysis showed that the incidence of pulmonary infection (OR=0.286, P=0.014), lower levels of mean platelet volume (OR=1.290, P=0.048), higher levels of fibrinogen (OR=0.444, P=0.004), BUN (OR=0.959, P=0.034) and systolic blood pressure (OR=0.970, P=0.013) were the independent risk factors of bleeding in the very old male patients with stage 5 CKD (P<0.05). All patients were followed up for 12 months. The proportion of all causes of death at the 3rd month, and bleeding events at the 3rd or 12th month, and recurrent major bleeding events at the 12th month were significantly higher in the hemorrhage group than those in the non-hemorrhage group. Conclusions: Very old male patients with stage 5 CKD are prone to bleeding complications, and have more possibilities to bleed again. Pulmonary infection, average volume of blood platelet, fibrinogen, BUN, and systolic blood pressure were the independent risk factors of bleeding in these patients.

[High glucose reduced the repair function of kidney stem cells conditional medium to the hypoxia-injured renal tubular epithelium cells].

OBJECTIVE: To evaluate the impacts of high glucose on the repair function of kidney stem cells (KSC) conditional medium to the hypoxia-injured renal tubular epithelium cells (RTEC). METHODS: KSC were isolated from the renal papilla in 4-week-Sprague-Dawley rats. The KSC were pretreated in media with high glucose (30 mmol/L) or with normal glucose (5.6 mmol/L), respectively. The supernatants of the pre-treated KSC were collected as the conditional media. The hypoxia/reoxygenation (H/R) model of rat RTEC was established using the NRK-52E cell line. The effects of KSC conditional media on the H/R RTEC were investigated. RESULTS: (1) The best H/R model of RTEC was established using hypoxia for 4 h and reoxygenation 2 h. (2) After hypoxia, the early and late cell apoptosis rates of the H/R RTEC were increased. The H/R RTEC were co-cultured with KSC conditional media for 12 h and 24 h, respectively. The H/R RTEC were co-cultured with DMEM/F12 as a control group. The cell apoptosis rate of H/R RTEC was lower after co-cultured with KSC conditional media (P<0.01), and the cell apoptosis rate of H/R RTEC in high glucose group was much higher than that in normal glucose group after co-cultured 24 h (P=0.02). (3) After hypoxia, the lactic dehydrogenase (LDH) and malondialdehyde (MDA) levels of the H/R RTEC supernatant were increased, and the superoxide dismutase (SOD) level decreased. The LDH and MDA levels were lower and the SOD level was higher after co-cultured with KSC conditional media for 12 h and 24 h, respectively (P<0.01). The LDH and MDA levels of H/R RTEC supernatant were much higher in the high glucose group than in the normal glucose group (P<0.05), and the SOD level of H/R RTEC supernatant was much lower in the high glucose group than in the normal glucose group (P<0.01). CONCLUSION: KSC conditional media could repair the H/R injury of RTEC. The effects were mainly by inhibiting cell apoptosis, and reducing oxidative stress; the anti-cell apoptosis ability and the anti-oxidative stress capacity of the conditional medium were reduced after KSC were pre-treated with high glucose.

Comparisons of different myosin heavy chain types, AMPK, and PGC-1α gene expression in the longissimus dorsi muscles in Bama Xiang and Landrace pigs.

Bama Xiang and Landrace pigs are the local fatty and lean breeds, respectively, in China. We compared differences in carcass traits, meat quality traits, and myosin heavy chain (MyHC) types in the longissimus dorsi muscles between Bama Xiang and Landrace pigs. This was done in pigs of the same age, using real-time PCR, to investigate the relationship between MyHC fiber types and carcass characteristics, meat quality traits, and the key factors regulating muscle fiber type. Bama Xiang pigs exhibited smaller size and slower growth than Landrace pigs (P < 0.01). We found that the superior meat quality, especially the high intramuscular fat (IMF) content in Bama Xiang pig, was related to elevated type I oxidative muscle fiber content (P < 0.01). In contrast, Landrace pig muscle had a higher glycolytic type IIb muscle fiber content (P < 0.01). MyHC I gene expression was significantly positively correlated with backfat thickness and IMF content (P < 0.01). MyHC IIb was significantly negatively correlated with IMF content (P < 0.05), and positively correlated with carcass yield (P < 0.05). AMP-activated protein kinase and peroxisome proliferator-activated receptor-g coactivator-1a are suggested to be the two key factors regulating muscle fiber type in pigs. Our results indicate that muscle fiber composition is one of the key differences leading to the differences of meat quality between Bama Xiang and Landrace pigs. These results may provide a theoretical basis for further studies of the molecular mechanism underlying the excellent meat quality of the Bama Xiang pig.

Schwann-like cell differentiation of rat adipose-derived stem cells by indirect co-culture with Schwann cells in vitro.

OBJECTIVES: Schwann cell (SC) transplantation is a promising therapy for peripheral nerve transaction, however, clinical use of SCs is limited due to their very limited availability. Adipose-derived stem cells (ADSCs) have been identified as an alternative source of adult stem cells in recent years. The aim of this study was to evaluate the feasibility of using ADSCs as a source of stem cells for differentiation into Schwann-like cells by an indirect co-culture approach, in vitro. MATERIALS AND METHODS: Multilineage differentiation potential of the obtained ADSCs was assayed by testing their ability to differentiate into osteoblasts and adipocytes. The ADSCs were co-cultured with SCs to be induced into Schwann-like cells through proximity, using a Millicell system. Expression of typical SC markers S-100, GFAP and P75NTR of the treated ADSCs was determined by immunocytochemical staining, western blotting and RT-PCR. Myelination capacity of the differentiated ADSCs (dADSCs) was evaluated in dADSC/dorsal root ganglia neuron (DRGN) co-cultures. RESULTS: The treated ADSCs adopted a spindle shaped-like morphology after co-cultured with SCs for 6 days. All results of immunocytochemical staining, western blotting and RT-PCR showed that the treated cells expressed S-100, GFAP and P75NTR, indications of differentiation. dADSCs could form Schwann-like cell myelin in co-culture with DRGNs. Undifferentiated ADSCs (uADSCs) did not form myelin compared to DRGNs cultured alone, but could produce neurite extension. CONCLUSIONS: These results demonstrate that this indirect co-culture microenvironment could induce ADSCs to differentiate into Schwann-like cells in vitro, which may be beneficial for treatment of peripheral nerve injuries in the near future.

Protective role of tretinoin and N-acetyl-L-cysteine from antiproliferative action of cigarette smoke extract on alveolar epithelial cells.

To investigate the mechanisms by which tretinoin and N-acetyl-L-cysteine (NAC) reverse the growth inhibition of alveolar epithelial cells induced by cigarette smoke extract (CSE), MTT assay was used to evaluate cell viability. It was observed that both tretinoin and NAC could restore the viability of CSE-inhibited A549 cells. By incubation with fluorescent indicator H2DCFDA, it was documented that CSE-stimulated accumulation of intracellular reactive oxygen species (ROS) was obviously decreased by tretinoin or NAC. Furthermore, using semi-quantitative and real-time quantitative RT-PCR as well as western blot methods, high expression of insulin-like growth factor binding protein-2 (IGFBP-2) in A549 cells treated with CSE was found at both transcriptional and protein levels, and concomitant with the restoration of cell growth after treatment with tretinoin or NAC, down regulation of IGFBP-2 was observed. From the present study, it is concluded that both RA and NAC can antagonize CSE-induced growth arrest of alveolar epithelial cells and that down regulation of IGFBP-2 may play an important role in the process.

Combined transplantation of neural stem cells and olfactory ensheathing cells for the repair of spinal cord injuries.

Spinal cord repair is a problem that has long puzzled neuroscientists. The failure of the spinal cord to regenerate and undergo reconstruction after spinal cord injury (SCI) can be attributed to secondary axonal demyelination and neuronal death followed by cyst formation and infarction as well as to the nature of the injury environment, which promotes glial scar formation. Cellular replacement and axon guidance are both necessary for SCI repair. Multipotent neural stem cells (NSCs) have the potential to differentiate into both neuronal and glial cells and are, therefore, likely candidates for cell replacement therapy following SCI. However, NSC transplantation alone is not sufficient for spinal cord repair because the majority of the NSCs engrafted into the spinal cord have been shown to differentiate with a phenotype which is restricted to glial lineages, further promoting glial scaring. Olfactory ensheathing cells (OECs) are a unique type of glial cell that occur both peripherally and centrally along the olfactory nerve. The ability of olfactory neurons to grow axons in the mature central nervous system (CNS) milieu has been attributed to the presence of OECs. It has been shown that transplanted OECs are capable of migrating into and through astrocytic scars and thereby facilitating axonal regrowth through an injury barrier. Given the complementary properties of NSCs and OECs, we predict that the co-transplantation of NSCs and OECs into an injured spinal cord would have a synergistic effect, promoting neural regeneration and functional reconstruction. The lost neurocytes would be replaced by NSCs, while the OECs would build "bridges" crossing the glial scaring that conduct axon elongation and promote myelinization simultaneously. Furthermore, the two types of cells could first be seeded into a bioactive scaffold and then the cell seeded construct could be implanted into the defect site. We believe that this type of treatment would lead to improved neural regeneration and functional reconstruction after SCI.

Protective effects of extract of Ginkgo biloba (EGb 761) on nerve cells after spinal cord injury in rats.

STUDY DESIGN: An experimental animal model was used to assess spinal cord injury following lateral hemitransection at thoracic spinal cord level. OBJECTIVE: To determine whether extract of Ginkgo biloba (EGb) could have a neuroprotective effect in spinal cord injury (SCI) in rats. SETTING: Department of Biological Sciences and Biotechnology, Tsinghua University, China. METHODS: A total of 72 adult rats were divided randomly into three groups: the EGb group, normal saline (NS) group, and sham operation group (sham group). After thoracic spinal cord hemitransection was performed at the level of the 9th thoracic vertebra (T9), rats in the EGb group were given 100 mg/kg EGb 761 daily, while rats in the NS group received NS. The rats in the sham group only underwent laminectomy without spinal cord hemitransection. At various time points after surgery, thoracic spinal cords were sampled and sliced for histochemistry, immunohistochemistry of inducible nitric oxide synthase (iNOS), and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) of apoptotic cells. RESULTS: Myelin staining showed that the area of cavities was small and the demyelinated zones were limited at and around the injury site of the spinal cord in the EGb group, while the area of cavities was large and the demyelinated zones were serious in the NS group. Nissl staining showed that the ratio of bilateral ventral horn neurons (transection side/uninjured side) in the EGb group was higher than that in the NS group (P<0.05). The apoptotic index and the percentage of iNOS-positive cells were lower in the EGb group than in the NS group. Furthermore, the percentage of iNOS-positive cells positively correlated with the apoptotic index (r( 2)=0.729, P<0.01) after SCI. CONCLUSION: This study demonstrated that EGb 761 could inhibit iNOS expression and have neuroprotective effect by preventing nerve cells from apoptosis after SCI in rats.

Black box radiation gauges and analyzers: dream or reality?

This paper describes our attempts to make radiation gauges and analyzers operate in more of a 'black box' manner-being more independent of or at least more insensitive to changes in such things as sample composition and position. Our overall approach relies heavily on Monte Carlo simulation and that is discussed first in relation to radiation gauge and analyzer design and usage. Then the principles and applications of radiation gauges and analyzers including the Measurement Chi-Square and Monte Carlo Library Least-Squares, respectively, are treated. Finally, future work in this area is discussed.

Development of the specific purpose Monte Carlo code CEARXRF for the design and use of in vivo X-ray fluorescence analysis systems for lead in bone.

X-ray fluorescence (XRF) systems have been increasingly used for in vivo toxic trace-element analysis in the human body, such as lead in the tibia. Monte Carlo simulation can provide an efficient and flexible method for designing and using in vivo XRF systems. The Monte Carlo code CEARXRF has been developed specifically to simulate the complete pulse height spectrum of energy-dispersive XRF systems. This code is capable of tracking photons in a general geometry and modelling all of the physics of photon interactions in the energy range 1-150 keV for elements Z = 1-94, including primary and higher degree excitations of K and L XRF, the Doppler broadening of Compton-scattered photon energies, and the polarization effects in low-energy photon scatterings. The scattering background for minimum detectable concentration (MDC) analysis may be simulated more accurately by taking into account Doppler broadening in the distribution of the Compton-scattered photon energy due to electron-binding effects. The use of polarized excitation photons has been shown to be important in producing a low scattering background and good measurement sensitivity. The code has two very unique and important features: (1) complete composition and density correlated sampling that is extremely useful for studying measurement sensitivity to small changes in sample composition and density; and (2) Monte Carlo library spectra calculation for the determination of elemental amounts by the Monte Carlo-Library Least-Squares (MCLLS) method. The capability of CEARXRF to aid the design and optimization of in vivo XRF analysis has been verified by modelling hypothesized lead K and L XRF measurement systems.

Optimization of in vivo X-ray fluorescence analysis methods for bone lead by simulation with the Monte Carlo code CEARXRF.

In the design of X-ray fluorescence (XRF) systems for in vivo measurements of lead in human bone, the most important considerations are the minimum detectable concentration (MDC), and accuracy and precision. Possible design optimizations can be investigated much more easily and economically by Monte Carlo simulation than by experiment. The specific purpose Monte Carlo code CEARXRF has been used in the present study for: (1) improving the MDC of a hypothesized in vivo 109Cd source-based KXRF system and a 109Cd source or X-ray tube source-based LXRF system by investigating the effects of source polarization and source-bone-detector geometry modification on reducing the scattering background, and (2) investigating the effects of sample variables, such as overlying skin thickness on the MDC and the lead XRF intensity precision. In addition, the feasibility of the Monte Carlo-Library Least-Squares (MCLLS) approach has been investigated in a preliminary fashion for 109Cd-based KXRF spectroscopy analysis.