[Epidemiological investigation of iron deficiency among preschool children in 10 provinces, autonomous regions, or municipalities in China].

Objective: To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China. Methods: A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test. Results: A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) µg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region (χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference (χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) (χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant (χ2=0.51, P=0.476). Conclusions: There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma

Selinexor is a selective inhibitor of nuclear export with anti-cancer properties. We performed a phase I study to determine the safety and maximum tolerated dose (MTD) of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory (R/R) T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL). Patients with R/R TCL and NKTL were treated with standard dose ICE, dexamethasone 20mg on days 3 to 7, and escalating doses of oral selinexor on days 3, 5 and 7 in a 3+3 design. Dose level (DL) 1, 2 and 3 were 40, 60 and 80mg respectively. Eleven patients with a median age of 60 were enrolled; 6 at DL1 and 5 at DL2. Patients had received a median of 2 (range 1-4) prior lines of treatment and 7 had primary refractory disease at study entry. Patients received a median of 3 cycles (range 1-6) of selinexor-DICE. The most common grade (G) 1/2 toxicities included nausea (64%), fatigue (55%), and anorexia (45%) and the most common G 3/4 toxicities included thrombocytopenia (82%), anemia (82%), neutropenia (73%), and hyponatremia (73%). Two patients developed doselimiting toxicities at DL2 and one at DL1. Five patients discontinued treatment for reasons other than disease progression or lack of response. Of the 10 evaluable patients, the overall and complete response rates were 91% and 82% respectively. The MTD of selinexor was 40mg when combined with DICE. The combination showed promising CR rates in patients with R/R TCL and NKTL but was poorly tolerated.

[The role and significance of digital reconstruction technique in liver segments based on portal vein structure].

Objective: To study the segment of liver according to the large amount of three-dimensional(3D) reconstructive images of normal human livers and the vascular system, and to recognize the basic functional liver unit based on the anatomic features of the intrahepatic portal veins. Methods: The enhanced CT primitive DICOM files of 1 260 normal human livers from different age groups who treated from October 2013 to February 2017 provided by 16 hospitals were analyzed using the computer-aided surgery system.The 3D liver and liver vascular system were reconstructed, and the digital liver 3D model was established.The vascular morphology, anatomical features, and anatomical distributions of intrahepatic portal veins were statistically analyzed. Results: The digital liver model obtained from the 3D reconstruction of CAS displayed clear intrahepatic portal vein vessels of level four.Perform a digital liver segments study based on the analysis of level four vascular distribution areas.As the less anatomical variation of left hepatic portal vein, the liver was classified into four types of liver segmentation mainly based on right hepatic portal vein.Type A was similar to Couinaud or Cho's segmentation, containing 8 segments(537 cases, 42.62%). Type B contained 9 segments as there are three ramifications of right-anterior portal vein(464 cases, 36.82%). The main difference for Type C was the variation of right-posterior portal vein which was sector shape(102 cases, 8.10%). Type D contained the cases with special portal vein variations, which needs three-dimensional simulation to design individualized liver resection plan(157 cases, 12.46%). These results showed that there was no significant difference in liver segmental typing between genders(χ(2)=2.179, P=0.536) and did not reveal any significant difference in liver segmental typing among the different age groups(χ(2)=0.357, P=0.949). Conclusions: The 3D digital liver model can demonstrate the true 3D anatomical structures, and its spatial vascular variations.The observation of anatomic features, distribution areas of intrahepatic portal veins and individualized liver segmentation achieved via digital medical 3D visualization technology is of great value for understand the complexity of liver anatomy and to guide the precise hepatectomy.

Activation of the Renin-Angiotensin System Promotes Colitis Development.

The renin-angiotensin system (RAS) plays pathogenic roles in renal and cardiovascular disorders, but whether it is involved in colitis is unclear. Here we show that RenTgMK mice that overexpress active renin from the liver developed more severe colitis than wild-type controls. More than 50% RenTgMK mice died whereas all wild-type mice recovered. RenTgMK mice exhibited more robust mucosal TH17 and TH1/TH17 responses and more profound colonic epithelial cell apoptosis compared to wild-type controls. Treatment with aliskiren (a renin inhibitor), but not hydralazine (a smooth muscle relaxant), ameliorated colitis in RenTgMK mice, although both drugs normalized blood pressure. Chronic infusion of angiotensin II into wild-type mice mimicked the severe colitic phenotype of RenTgMK mice, and treatment with losartan [an angiotensin type 1 receptor blocker (ARB)] ameliorated colitis in wild-type mice, confirming a colitogenic role for the endogenous RAS. In human biopsies, pro-inflammatory cytokines were suppressed in patients with inflammatory bowel disease who were on ARB therapy compared to patients not receiving ARB therapy. These observations demonstrate that activation of the RAS promotes colitis in a blood pressure independent manner. Angiotensin II appears to drive colonic mucosal inflammation by promoting intestinal epithelial cell apoptosis and mucosal TH17 responses in colitis development.

A smoking cessation intervention among tuberculosis patients in rural China.

OBJECTIVE: To assess the integration of a smoking cessation intervention into routine tuberculosis (TB) services. METHOD: Consecutive TB patients registered from 1 March to 31 August 2010 were enrolled in an intervention for self-reported smoking to promote tobacco cessation during treatment for TB. Information on the harmful health effects of tobacco smoke and smoking and TB were provided to TB patients who self-reported as current smokers. Smoking status was reassessed at every follow-up visit during anti-tuberculosis treatment with reinforced health messages and advice to quit. RESULTS: Of 800 TB patients enrolled, 572 (71.5%) were male and 244 (30.5%) were current smokers. Females were more likely to be non-smokers (100% vs. 35.8%, P < 0.001). Of the 244 current smokers, 144 (59.0%) started smoking at <20 years, 197 (80.7%) consumed ⩾20 cigarettes per day, 211 (86.5%) had perceived smoking dependence and 199 (81.6%) had made no attempt to quit before the diagnosis of TB. Of the 244 current smokers, 234 (95.9%) were willing to quit, and 156 (66.7%) reported abstinence at month 6. Challenges to implementing smoking cessation intervention were identified. CONCLUSION: The majority of current smokers among TB patients were willing to quit and remained abstinent at the end of anti-tuberculosis treatment. This intervention should be scaled up nationwide.

Objectif : Evaluer la possibilité d'intégrer une intervention d'arrêt du tabac dans les services de routine de la tuberculose (TB).Méthode : Les patients tuberculeux consécutifs inscrits entre le 1e mars et le 31 août 2010 ont été enrôlés dans une intervention visant à promouvoir l'arrêt du tabac chez ceux qui disaient fumer pendant le traitement de leur TB. Des informations sur les effets sanitaires dangereux de la fumée de tabac et sur le fait de fumer en étant tuberculeux ont été fournies aux patients qui se sont dit fumeurs actuels. Le statut en matière de tabac a été réévalué à chaque visite de suivi pendant le traitement antituberculeux avec des messages sanitaires renforcés et des conseils visant à l'arrêt.Résultats : Sur 800 patients TB enrôlés, 572 (71,5%) étaient des hommes et 244 (30,5%) étaient des fumeurs actuels. Les femmes étaient plus souvent non fumeuses (100% contre 35,8% ; P < 0,001). Des 244 fumeurs actuels, 144 (59,0%) avaient commencé à fumer avant 20 ans, 197 (80,7%) consommaient ⩾20 cigarettes par jour, 211 (86,5%) étaient conscients de leur dépendance au tabac et 199 (81,6%) n'avaient jamais essayé d'arrêter avant le diagnostic de TB. Des 244 fumeurs actuels, 234 (95,9%) voulaient arrêter et 156 (66,7%) ont déclaré être toujours abstinents à 6 mois. Les défis à la mise en œuvre d'une intervention d'arrêt du tabac ont été identifiés.Conclusion : La majorité des fumeurs actuels parmi les patients TB voulaient arrêter et sont restés abstinents à la fin du traitement antituberculeux. Cette intervention devrait être étendue au pays tout entier.

Objetivo: Evaluar la utilidad de la integración de las intervenciones de promoción del abandono del tabaquismo en los servicios ordinarios de atención de la tuberculosis (TB).Métodos: Se inscribieron de manera consecutiva los pacientes con diagnóstico de TB y tabaquismo actual del 1° de marzo al 31 de agosto del 2010 en una intervención cuyo objeto era a promover el abandono del hábito tabáquico durante el tratamiento antituberculoso. Se suministró información acerca de los efectos deletéreos del humo del tabaco sobre la salud y de la asociación del tabaquismo y la TB a los pacientes que autorrefirieron un tabaquismo actual. En cada consulta de seguimiento durante el tratamiento se evaluó de nuevo la situación frente al tabaco, se reforzaron los mensajes sobre la salud y se reiteró el consejo de abandonar el hábito.Resultados: De los 800 pacientes con TB inscritos, 572 fueron de sexo masculino (71,5%) y 244 eran fumadores actuales (30,5%). Las mujeres fueron con mayor frecuencia no fumadoras (100% contra 35,8%; P < 0,001). De los 244 fumadores actuales, 144 habían comenzado a fumar antes de los 20 años de edad (59,0%), 197 consumían ⩾20 cigarrillos por día (80,7%), 211 habían percibido la dependencia al tabaquismo (86,5%) y 199 nunca habían intentado abandonar el hábito antes del diagnóstico de TB (81,6%). De los 244 fumadores actuales, 234 estaban dispuestos a abandonar el tabaco (95,9%) y 156 notificaron abstinencia al sexto mes (66,7%). Se pusieron de manifiesto obstáculos a la aplicación de la intervención en favor del abandono del tabaquismo.Conclusión: En su mayoría, los fumadores actuales entre los pacientes con diagnóstico reciente de TB estaban dispuestos a abandonar el tabaquismo y cumplieron con la abstinencia hasta el final del tratamiento antituberculoso. Se debería ampliar la aplicación de esta intervención a escala nacional.

Trans-system mechanisms against ischemic myocardial injury.

A mammalian organism possesses a hierarchy of naturally evolved protective mechanisms against ischemic myocardial injury at the molecular, cellular, and organ levels. These mechanisms comprise regional protective processes, including upregulation and secretion of paracrine cell-survival factors, inflammation, angiogenesis, fibrosis, and resident stem cell-based cardiomyocyte regeneration. There are also interactive protective processes between the injured heart, circulation, and selected remote organs, defined as trans-system protective mechanisms, including upregulation and secretion of endocrine cell-survival factors from the liver and adipose tissue as well as mobilization of bone marrow, splenic, and hepatic cells to the injury site to mediate myocardial protection and repair. The injured heart and activated remote organs exploit molecular and cellular processes, including signal transduction, gene expression, cell proliferation, differentiation, migration, mobilization, and/or extracellular matrix production, to establish protective mechanisms. Both regional and trans-system cardioprotective mechanisms are mediated by paracrine and endocrine messengers and act in coordination and synergy to maximize the protective effect, minimize myocardial infarction, and improve myocardial function, ensuring the survival and timely repair of the injured heart. The concept of the trans-system protective mechanisms may be generalized to other organ systems-injury in one organ may initiate regional as well as trans-system protective responses, thereby minimizing injury and ensuring the survival of the entire organism. Selected trans-system processes may serve as core protective mechanisms that can be exploited by selected organs in injury. These naturally evolved protective mechanisms are the foundation for developing protective strategies for myocardial infarction and injury-induced disorders in other organ systems.

Endocrine protection of ischemic myocardium by FGF21 from the liver and adipose tissue.

Myocardial ischemia, while causing cardiomyocyte injury, can activate innate protective processes, enhancing myocardial tolerance to ischemia. Such processes are present in not only the heart, but also remote organs. In this investigation, we demonstrated a cardioprotective process involving FGF21 from the liver and adipose tissue. In response to myocardial ischemia/reperfusion injury in the mouse, FGF21 was upregulated and released from the hepatic cells and adipocytes into the circulation and interacted with FGFR1 in cardiomyocytes under the mediation of the cell membrane protein ß-Klotho, inducing FGFR1 phosphorylation. This action caused phosphorylation of the signaling molecules PI3K p85, Akt1, and BAD, thereby reducing caspase 3 activity, cell death, and myocardial infarction in association with improvement of myocardial function. These observations suggest that FGF21 is upregulated and released from the liver and adipose tissue in myocardial injury, contributing to myocardial protection by the mediation of the FGFR1/ß-Klotho-PI3K-Akt1-BAD signaling network.

The iron distribution and magnetic properties of schistosome eggshells: implications for improved diagnostics.

BACKGROUND: Schistosoma mansoni and Schistosoma japonicum are the most frequent causative agents of human intestinal schistosomiasis. Approximately 200 million people in the world are infected with schistosomes. Diagnosis of schistosomiasis is often difficult. High percentages of low level infections are missed in routine fecal smear analysis and current diagnostic methodologies are inadequate to monitor the progress of parasite control, especially in areas with low transmission. Improved diagnostic methods are urgently needed to evaluate the success of elimination programs. Recently, a magnetic fractionation method for isolation of parasite eggs from feces was described, which uses magnetic microspheres to form parasite egg - magnetic microsphere conjugates. This approach enables screening of larger sample volumes and thus increased diagnostic sensitivity. The mechanism of formation of the conjugates remains unexplained and may either be related to specific surface characteristics of eggs and microspheres or to their magnetic properties. METHODS/PRINCIPAL FINDINGS: Here, we investigated iron localization in parasite eggs, specifically in the eggshells. We determined the magnetic properties of the eggs, studied the motion of eggs and egg-microsphere conjugates in magnetic fields and determined species specific affinity of parasite eggs to magnetic microspheres. Our study shows that iron is predominantly localized in pores in the eggshell. Parasite eggs showed distinct paramagnetic behaviour but they did not move in a magnetic field. Magnetic microspheres spontaneously bound to parasite eggs without the presence of a magnetic field. S. japonicum eggs had a significantly higher affinity to bind microspheres than S. mansoni eggs. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the interaction of magnetic microspheres and parasite eggs is unlikely to be magnetic in origin. Instead, the filamentous surface of the eggshells may be important in facilitating the binding. Modification of microsphere surface properties may therefore be a way to optimize magnetic fractionation of parasite eggs.

Correlation of tumor relapse and elevated expression of survivin and vascular endothelial growth factor in superficial bladder transitional cell carcinoma.

Survivin and vascular endothelial growth factor (VEGF) are newly discovered tumor markers closely correlated with bladder cancer. We analyzed the expression of survivin and VEGF in paraffin-embedded tumor tissues from 78 patients with bladder transitional cell carcinoma (BTCC) using an immunohistochemistry method. Normal bladder mucosae from 10 non-BTCC cases were also included as a control group. All patients were closely followed up for tumor recurrence after undergoing transurethral resection of bladder tumor procedures. The positive expression rates of survivin and VEGF in superficial BTCC were 66.7% (52/78) and 69.2% (54/78), respectively, which were significantly higher than those in the control group, 0% (0/10). A positive correlation was found between survivin and VEGF expression (r = 0.283, P < 0.01). Thirty-two of 78 patients (41.0%) displayed recurrence during follow-up (median: 47; range: 7-62 months). The tumor recurrence rate in survivin(+) patients was 53.8% (28/52), which was significantly higher than that in survivin(-) patients [15.4% (4/26); P < 0.05]. The recurrence rate in VEGF(+)/ VEGF(-) patients was 50.0% (27/54) and 20.8% (5/24), respectively (P < 0.05). The sensitivity for predicting the relapse of superficial BTCC was 87.5% in the survivin(+) group, 84.4% in the VEGF(+) group, and 78.1% in the survivin(+)/VEGF(+) group, and the specificity was 47.8, 41.3, and 65.2%, respectively. Survivin and VEGF interact and jointly regulate the biological behavior of bladder cancer. Our results suggest that overexpression of survivin and VEGF accompany a higher risk of BTCC recurrence, making survivin and VEGF biomarkers for predicting the relapse of bladder cancer.

Vitamin D receptor signaling inhibits atherosclerosis in mice.

Although vitamin D has been implicated in cardiovascular protection, few studies have addressed the role of vitamin D receptor (VDR) in atherosclerosis. Here we investigate the effect of inactivation of the VDR signaling on atherogenesis and the antiatherosclerotic mechanism of vitamin D. Low density lipoprotein receptor (LDLR)(-/-)/VDR(-/-) mice exhibited site-specific accelerated atherogenesis, accompanied by increases in adhesion molecules and proinflammatory cytokines in the aorta and cholesterol influx in macrophages. Macrophages showed marked renin up-regulation in the absence of VDR, and inhibition of renin by aliskiren reduced atherosclerosis in LDLR(-/-)/VDR(-/-) mice, suggesting that the renin-angiotensin system (RAS) promotes atherosclerosis in the absence of VDR. LDLR(-/-) mice receiving LDLR(-/-)/VDR(-/-) BMT developed larger lesions than LDLR(-/-) BMT controls. Moreover, LDLR(-/-) mice receiving Rag-1(-/-)/VDR(-/-) BMT, which were unable to generate functional T and B lymphocytes, still had more severe atherosclerosis than Rag-1(-/-) BMT controls, suggesting a critical role of macrophage VDR signaling in atherosclerotic suppression. Aliskiren treatment eliminated the difference in lesions between Rag-1(-/-)/VDR(-/-) BMT and Rag-1(-/-) BMT recipients, indicating that local RAS activation in macrophages contributes to the enhanced atherogenesis seen in Rag-1(-/-)/VDR(-/-) BMT mice. Taken together, these observations provide evidence that macrophage VDR signaling, in part by suppressing the local RAS, inhibits atherosclerosis in mice.

FGFR4 Gly388Arg polymorphism contributes to prostate cancer development and progression: a meta-analysis of 2618 cases and 2305 controls.

BACKGROUND: Fibroblast growth factor receptor 4 (FGFR4) displays multiple biological activities, including mitogenic and angiogenic activity, and plays important roles in the etiology and progression of prostate cancer. Gly388Arg polymorphism in FGFR4 gene has been reported to be involved in prostate cancer incidence and aggressiveness in several studies. To derive a more precise estimation of the relationship, a meta-analysis was performed. METHODS: Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. RESULTS: The Arg388 allele increased prostate cancer risk compared with Gly388 allele (OR = 1.17, 95% CI = 1.07-1.29). When stratified by race, there was a significantly increased prostate cancer risk in Asian and Caucasian populations. Moreover, prostate cancer patients with Arg/Arg genotype had a 1.34-fold increased risk of advanced prostate cancer (95% CI: 1.03-1.74) compared with those with Gly/Gly+Gly/Arg genotype. CONCLUSION: This meta-analysis showed the evidence that FGFR4 Gly388Arg polymorphism was associated with an increased risk of prostate cancer development and progression, suggesting that FGFR4 Gly388Arg polymorphism could be a marker for prostate cancer development and progression.

Cardioprotective mechanisms activated in response to myocardial ischemia.

Myocardial ischemia, a disorder causing myocardial infarction and malfunction, can activate various adaptive mechanisms that protect cardiomyocytes from ischemic injury. During the early hours post myocardial ischemia, injured cardiac cells can release several molecules, including adenosine, opioids, and bradykinin, which promote myocardial survival by activating the G protein signaling pathways. During a later phase about several days, myocardial ischemia induces upregulation of growth factors and cytokines, including VEGF, ILGF, HGF, and SDF-1, in the injured myocardium, contributing to cardioprotection. In addition to the injured heart, the liver participates in cardioprotection. In response to myocardial ischemia, the liver upregulates and releases secretory proteins, including FGF21 and TFF3, both of which promote cardiomyocyte survival. The liver also provides a reservoir of hepatic cells that mobilize to the site of myocardial ischemia, potentially contributing to cardioprotection. Taken together, the early and late mechanisms act coordinately in a time-dependent manner, ensuring effective cardioprotection post myocardial infarction. Investigations on these innate cardioprotective mechanisms have provided insights into the development of cardioprotective strategies for treating myocardial infarction. In this article, the authors review the innate mechanisms of cardioprotection in myocardial ischemia.

Elastic laminae in vascular development and disease.

The activities of vascular cells, including adhesion, proliferation, and migration, are mediated by extracellular matrix components, including collagen matrix and elastic fibers or laminae. Whereas the collagen matrix stimulates vascular cell adhesion, proliferation, and migration, the elastic laminae inhibit these activities. Coordinated regulation of cell activities by these matrix components is an essential process for controlling the development and remodeling of the vascular system. This article summarizes recent development on the role of arterial elastic laminae in regulating the development of smooth muscle-like cells from bone marrow-derived progenitor cells as well as in mediating cell adhesion, proliferation, and migration with a focus on the molecular mechanisms and physiological significance.

Formation of smooth muscle alpha actin filaments in CD34+ bone marrow cells on arterial elastic laminae: potential role of SH2 domain-containing protein tyrosine phosphatase-1.

Arterial smooth muscle cells (SMCs) are present in the elastic lamina-containing media, suggesting that the elastic laminae may regulate the development of SMCs. Here, we investigated the role of elastic laminae in regulating the formation of SM alpha actin filaments in mouse CD34+ bone marrow cells and the role of a protein tyrosine phosphatase, SH2 domain-containing protein tyrosine phosphatase (SHP)-1, in the mediation of this process. Mouse CD34+ bone marrow cells were isolated by magnetic separation and used for assessing the influence of elastic laminae and collagen matrix on the formation of SM alpha actin filaments. CD34+ cells with transgenic SHP-1 knockout or siRNA-mediated SHP-1 knockdown were used to assess the role of SHP-1 in mediating the formation of SM alpha actin filaments. In cell culture tests, elastic laminae, but not collagen matrix, stimulated the formation of SM alpha actin filaments in CD34+ cells. The phosphatase SHP-1 mediated the stimulatory effect of elastic laminae. The interaction of CD34+ cells with elastic laminae, but not with collagen matrix, induced activation of SHP-1. The suppression of SHP-1 by transgenic SHP-1 knockout or siRNA-mediated SHP-1 knockdown significantly reduced the formation of SM alpha actin filaments in CD34+ cells cultured on elastic laminae. The in vitro observations were confirmed by using an in vivo model of implantation of elastic lamina and collagen matrix scaffolds into the aorta. These observations suggest that elastic laminae stimulate the formation of SM alpha actin filaments in CD34+ bone marrow cells and SHP-1 mediates the stimulatory effect of elastic laminae.

Differential expression of survivin splice isoforms in medulloblastomas.

Survivin, a member of the inhibitor of apoptosis protein family, is implicated in the dysregulation of apoptosis in human cancers. Survivin and survivin-deltaEx3, one of its two alternatively spliced isoforms, confer anti-apoptotic activities in human tumours, while survivin-2B antagonizes such anti-apoptotic properties. The current study was undertaken to examine the mRNA expression of survivin isoforms and their correlation with clinical staging and outcome in 20 medulloblastoma (MB) tumours, three MB cell lines and normal brain tissues (a foetal and an adult cerebellum) by densitometry scanning of 32p-dCTP incorporated reverse transcription polymerase chain reaction (RT-PCR) products and quantitative real-time PCR. Our results showed that the normal adult brain only expressed low levels of survivin-deltaEx3 mRNA, while the foetal brain expressed all three isoforms, with wild-type survivin as the dominant transcript. All three survivin isoforms were detected in all the MB cell lines and tumours analysed. Immunohistochemical staining also demonstrated survivin protein expressions in all five paraffin-embedded MBs, with predominant nuclear localization. Although overexpressions of survivin were not associated with the presence of metastatic MB or tumour histological subtypes, elevated expressions of survivin-deltaEx3 were significantly associated with progressive/recurrent tumours (P-value = 0.024). Our data demonstrated that overexpression of survivin mRNA is a common feature in MBs, may contribute to their anti-apoptosis properties and clinical behaviours, and predicts a poor clinical outcome, independent of clinical staging or tumour histology.

Long-term trends in Indigenous deaths from chronic diseases in the Northern Territory: a foot on the brake, a foot on the accelerator.

OBJECTIVE: To examine trends in Northern Territory Indigenous mortality from chronic diseases other than cancer. DESIGN: A comparison of trends in rates of mortality from six chronic diseases (ischaemic heart disease [IHD], chronic obstructive pulmonary disease [COPD], cerebrovascular disease [CVD], diabetes mellitus [DM], renal failure [RF] and rheumatic heart disease [RHD]) in the NT Indigenous population with those of the total Australian population. PARTICIPANTS: NT Indigenous and total Australian populations, 1977-2001. MAIN OUTCOME MEASURES: Estimated average annual change in chronic disease mortality rates and in mortality rate ratios. RESULTS: Death rates from IHD and DM among NT Indigenous peoples increased between 1977 and 2001, but this increase slowed after 1990. Death rates from COPD rose before 1990, but fell thereafter. There were non-significant declines in death rates from CVD and RHD. Mortality rates from RF rose in those aged > or = 50 years. The ratios of mortality rates for NT Indigenous to total Australian populations from these chronic diseases increased throughout the period. CONCLUSIONS: Mortality rates from IHD and DM in the NT Indigenous population have been increasing since 1977, but there is evidence of a slower rise (or even a fall) in death rates in the 1990s. These early small changes give reason to hope that some improvements (possibly in medical care) have been putting the brakes on chronic disease mortality among Aboriginal and Torres Strait Islander peoples.

Statistical shape analysis of metopic craniosynostosis: a preliminary study.

This preliminary study was conducted to explore different analytical shape methods for use in evaluating children born with cranial vault deformities. Twenty skull outlines from patients with metopic craniosynostosis were ascribed landmarks. Scale, location, and rotational factors were removed using Procrustes analysis. A single index of severity from 0-5, with 5 being the most severe, was developed using Procrustes distance in shape space. Skull 20 had the highest score in our data set. Principal component analysis was performed to determine areas of large shape variability. Principal component 1 and 2 accounted for 86 % of the shape variability which was attributed to early closure of the metopic suture. Procrustes analysis used in combination with Procrustes distance and principal component analysis are powerful tools for the evaluation of cranial vault deformities and can be used to objectively categorize the severity of the skull deformity and outcome from surgical reconstructive surgery.

Negative regulation of monocyte adhesion to arterial elastic laminae by signal regulatory protein alpha and Src homology 2 domain-containing protein-tyrosine phosphatase-1.

Elastic laminae are extracellular matrix constituents that not only contribute to the stability and elasticity of arteries but also play a role in regulating arterial morphogenesis and pathogenesis. We demonstrate here that an important function of arterial elastic laminae is to prevent monocyte adhesion, which is mediated by the inhibitory receptor signal regulatory protein (SIRP) alpha and Src homology 2 domain-containing protein-tyrosine phosphatase (SHP)-1. In a matrix-based arterial reconstruction model in vivo, elastic laminae were resistant to leukocyte adhesion and transmigration compared with the collagen-dominant arterial adventitia. The density of leukocytes within the elastic lamina-dominant media was about 58-70-fold lower than that within the adventitia from 1 to 30 days. An in vitro assay confirmed the inhibitory effect of elastic laminae on monocyte adhesion. The exposure of monocytes to elastic laminae induced activation of SIRP alpha, which in turn activated SHP-1. Elastic lamina degradation peptides extracted from arterial specimens could also activate SIRP alpha and SHP-1. The knockdown of SIRP alpha and SHP-1 by specific small interfering RNA diminished the inhibitory effect of elastic laminae, resulting in a significant increase in monocyte adhesion. These observations suggest that SIRP alpha and SHP-1 potentially mediate the inhibitory effect of elastic laminae on monocyte adhesion.

Phase II randomized trial of autologous formalin-fixed tumor vaccine for postsurgical recurrence of hepatocellular carcinoma.

PURPOSE: We conducted a Phase II clinical trial with randomized patients to determine whether autologous formalin-fixed tumor vaccine (AFTV) protects against postsurgical recurrence of hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: Forty-one patients with HCC who had undergone curative resection were randomly allocated to the vaccine treatment (n = 19) or no adjuvant control group (n = 22). Three intradermal vaccinations were administered at 2-week intervals beginning 4-6 weeks after hepatic resection. A delayed-type hypersensitivity test was performed before and after vaccination. Primary and secondary end points are recurrence-free survival and overall survival, respectively. Observation continued until the majority of surviving patients had lived >12 months after the curative resection. RESULTS: In a median follow-up of 15 months, the risk of recurrence in vaccinated patients was reduced by 81% (95% confidence interval, 33-95%; P = 0.003). Vaccination significantly prolonged the time to first recurrence (P = 0.003) and improved recurrence-free survival (P = 0.003) and overall survival rates (P = 0.01). AFTV played a significant role in preventing recurrence in patients with small tumors. Adverse effects were limited to grade 1 or 2 skin toxicities such as erythema, dry desquamation, and pruritus. CONCLUSIONS: AFTV therapy is a safe, feasible, and effective treatment for preventing postoperational recurrence of HCC. Patients with low tumor burdens benefit from the treatment. This treatment should be advanced to a large-scale randomized trial.

An effective method for axillary bud culture and RAPD analysis of cloned plants in tetraploid black locust.

An efficient micropropagation technique by axillary bud multiplication was established for cloning tetraploid black locust tree (Robinia pseudoacacia L.). The result showed that the optimal medium for shoot multiplication and elongation was Murashige and Skoog (MS) medium supplemented with 0.5 mg/l 6-benzylaminopurine in combination with 0.5 mg/l kinetin and 0.1 mg/l 1-naphthaleneacetic acid. The best medium for rooting was half-strength MS medium with 0.25 mg/l indole-3-butyric acid. In the present report, we examined the genetic fidelity of the micropropagated plants by the randomly amplified polymorphic DNA (RAPD) method with 25 primers. The cloned plants of tetraploid black locust showed complete stability.