[Pay attention to clinical research, diagnosis and treatment of mixed cognitive impairment].

The concept of mixed cognitive impairment, which was put forward on the basis of mixed dementia, has wider implications. It emphasizes that cognitive impairment has not progressed to the early clinical stages of dementia. In recent years, the focus of dementia research has shifted to the "pre-dementia stage", and more attention has been paid to the influence of vascular factors on cognitive impairment. To a certain extent, vascular risk factors and cerebrovascular diseases can be intervened. Therefore, paying attention to the early clinical identification of mixed cognitive impairment, and strengthening the research and intervention of vascular factors in cognitive impairment has important clinical significance for the effective prevention and treatment of dementia.

Cardiac iron measurement and iron chelation therapy in patients with ß thalassaemia major: experience from Taiwan.

BACKGROUND: The aims of our study were to evaluate (i) the relationship between cardiac T2* values and cardiac complications in Asian ß-thalassaemia major (TM) patients, and (ii) the association between cardiac T2* values and other parameters currently used to predict cardiac complications as a result of transfusion iron overload. METHODS: We examined the myocardial iron loads of 88 TM patients from Taiwan with cardiac T2* magnetic resonance imaging (MRI) and assessed the correlation between cardiac T2* values and serum ferritin levels, liver iron concentration and left ventricular ejection fraction (LVEF). We also determined the predictive value of these measurements for the development of arrhythmia. RESULTS AND CONCLUSION: In our group of Taiwanese patients, the relative risk for arrhythmia was 10·36 when cardiac T2* values were less than 10 ms (compared with ≥10 ms) and 1·98 when serum ferritin levels increased >2500 ng mL(-1) (compared with ≤2500 ng mL(-1) ). Serum ferritin levels correlated with cardiac T2* values in patients with abnormal myocardial iron loads (T2* < 20 ms, r = -0·48, P = 0·004, n = 34), but LVEF (measured by echocardiography) gave no indication of excess myocardial iron deposition (r = -0·07, P = 0·52) or of the risk of developing arrhythmia.

[Morphological and histopathological evaluation of temporomandibular joint osteoarthrosis induced by perforation of articular disc in rats].

Objective: To establish the animal model of temporomandibular joint osteoarthrosis (TMJOA) in rats induced by perforation of articular disc and evaluate the morphological characteristics and histopathological changes of the condyle of temporomandibular joint (TMJ). Methods: Eight male SD rats, purchased from Chongqing Medical University, were marked from No. 1 to No. 8 according to a random number table. The eight numbered rats were then arranged according to their sizes from large to small. The first four rats were divided into the one-week group, while the last four were divided into the four-week group. In order to simulate a TMJ disc perforation, an oblique incision was created along the zygomatic arch of the left side (the model side) making the TMJ superior joint space exposed. The left disc was pulled out and artificially perforated by a dental round bur with 1.5 mm diameter at the postmedian part of TMJ disc. The disc of the right side (the control side) was kept intact. The rats were randomly euthanized respectively at 1 week or 4 weeks (n=4 for each time point) for further study. Morphological observation and imaging examination were used to assess the degree of articular cartilage degradation and the loss of subchondral bone. Immunohistochemicalstaining (IHC), safranin O and fast green staining, tartrate-resistant acid phosphatase (TRAP) staining and haematoxylin staining were performed to evaluate the histopathological changes of condylar cartilage. Results: In the morphological observation, significant redness and swelling were observed on the model side of the 1-week-group and the typical beak-like change of osteoarthropathy was observed on the model side of the 4-week-group. The heights of condylar process on the model sides in the 1-week-group and 4-week-group [(2.73±0.14) and (2.49±0.25) cm, respectively] were significantly lower than that in the control side [(3.30±0.09) and (3.30±0.12) cm, respectively] (P<0.01). Imaging examination showed obvious damage in trabecular microstructure on the model side of the 4-week-group. Safranin O and fast green staining showed that the amounts of proteoglycan on the model sides of the 1-week-group and the 4-week-group were significantly lower than that on the control sides (P<0.01). TRAP staining showed that the numbers of osteoclasts on the model side of the 1-week-group and the 4-week-group was significantly higher than that on the control sides (P<0.01). IHC staining and Haematoxylin staining showed that the mean optical densities of collagen on the model side of the 1-week-group and the 4-week-group was significantly reduced compared with that on the control sides (P<0.01), while the mean optical densities of matrix metalloproteinase increased significantly (P<0.01). Conclusions: After making a articular disc perforation, the condylar cartilage on the model side presented typical TMJOA pathological changes.

MIIP inhibits malignant progression of hepatocellular carcinoma through regulating AKT.

OBJECTIVE: This study was aimed to investigate the expression characteristics of MIIP in hepatocellular carcinoma (HCC), and to further explore whether it can inhibit the malignant progression of this disease via regulating AKT expression. PATIENTS AND METHODS: Real-time quantitative PCR (qRT-PCR) was performed to examine the expression of MIIP in tumor and paracancerous tissue specimens of 39 patients with HCC, and to analyze the interplay between MIIP expression and clinical indicators and prognosis of HCC patients. At the same time, in HCC cell lines, the expression of MIIP was further verified using qRT-PCR. In addition, MIIP overexpression and knockdown models were constructed using lentivirus in HCC cell lines (Bel-7402 and Hep3B), and the influence of MIIP on the biological function of HCC cells was analyzed through CCK-8 and transwell migration assays. Finally, luciferase reporting assay and cell reverse experiments were applied to further explore the potential molecular mechanism and the interaction between MIIP and AKT. RESULTS: The results of qRT-PCR showed that the expression level of MIIP in HCC tissue samples was remarkably lower than that in adjacent ones, with a statistically significant difference. Compared with patients with high expression of MIIP, patients with low MIIP expression had a higher occurrence of distant metastasis and a lower overall survival rate. Similarly, compared with control group, the proliferation and migration ability of HCC cells in MIIP knockdown group (sh-MIIP) was remarkably enhanced, while the opposite result was observed in MIIP overexpression group. In addition, qRT-PCR results also revealed that AKT and MIIP were negatively correlated in HCC tissues. At the same time, the results of luciferase reporter gene assay demonstrated that MIIP can be targeted by AKT through certain binding site. Additionally, cell reverse experiment found that there might exist a mutual regulation between MIIP and AKT, thereby jointly regulating the malignant progression of HCC. CONCLUSIONS: MIIP expression is remarkably decreased both in HCC tissues and cell lines; meanwhile, the low expression of MIIP is positively correlated with the occurrence of distant metastasis and poor prognosis of patients with HCC. In addition, MIIP may be able to inhibit the malignant progression of HCC by modulating AKT expression.

Improvement of the Irrigation Scheme in the ORCHIDEE Land Surface Model and Impacts of Irrigation on Regional Water Budgets Over China.

In China, irrigation is widespread in 40.7% cropland to sustain crop yields. By its action on water cycle, irrigation affects water resources and local climate. In this study, a new irrigation module, including flood and paddy irrigation technologies, was developed in the ORCHIDEE-CROP land surface model which describes crop phenology and growth in order to estimate irrigation demands over China from 1982 to 2014. Three simulations were performed including NI (no irrigation), IR (with irrigation limited by local water resources), and FI (with irrigation demand fulfilled). Observations and census data were used to validate the simulations. Results showed that the estimated irrigation water withdrawal ( W ) based on IR and FI scenarios bracket statistical W with fair spatial agreements ( r = 0 . 68 ± 0 . 07 ; p < 0 . 01 ). Improving irrigation efficiency was found to be the dominant factor leading to the observed W decrease. By comparing simulated total water storage (TWS) with GRACE observations, we found that simulated TWS with irrigation well explained the TWS variation over China. However, our simulation overestimated the seasonality of TWS in the Yangtze River Basin due to ignoring regulation of artificial reservoirs. The observed TWS decrease in the Yellow River Basin caused by groundwater depletion was not totally captured in our simulation, but it can be inferred by combining simulated TWS with census data. Moreover, we demonstrated that land use change tended to drive W locally but had little effect on total W over China due to water resources limitation.

Mutant Chinese hamster ovary cells pleiotropically defective in receptor-mediated endocytosis.

Populations of Chinese hamster ovary cells selected for resistance to diphtheria toxin were found to be highly enriched for mutants deficient in the uptake of lysosomal hydrolases via the mannose 6-phosphate receptor. One doubly defective mutant, DTF 1-5-1, exhibited increased resistance to Sindbis virus, although it was able to bind and internalize virus normally. Normal production of virus was obtained when, subsequent to virus binding, the mutant was exposed for 2 min to acidic pH. Similarly, a shift to acidic pH increased the sensitivity of DTF 1-5-1 to diphtheria toxin 12-fold. Decreased uptake of lysosomal hydrolases by the mutant correlated with decreased mannose 6-phosphate receptor activity at the cell surface; results of lactoperoxidase-catalyzed iodination indicated that the surface-associated receptor was present but inactive on DTF 1-5-1. Total mannose 6-phosphate receptor activity was also decreased in the mutant and this decrease was reflected by increased secretion of lysosomal hydrolases. The phenotype of DTF 1-5-1 resembles in many ways that of cells treated with ammonia. We suggest that the defect in DTF 1-5-1 stems from an inability to deliver virus, diphtheria toxin, and lysosomal hydrolases to an acidic compartment. Other ligands may be endocytosed through a different pathway since the defect of DTF 1-5-1 did not decrease the endocytosis of ricin, modeccin, or Pseudomonas toxin and had minimal effects on uptake and degradation of low density lipoprotein.

Functional characterization of a non-AUUUA AU-rich element from the c-jun proto-oncogene mRNA: evidence for a novel class of AU-rich elements.

AU-rich RNA-destabilizing elements (AREs) found in the 3' untranslated regions of many labile mRNAs encoding proto-oncoproteins and cytokines generally contain (i) one or more copies of the AUUUA pentanucleotide and (ii) a high content of uridylate and sometimes also adenylate residues. Recently, we have identified a potent ARE from the 3' untranslated region of c-jun proto-oncogene mRNA that does not contain the AUUUA motif. In an attempt to further our understanding of the general principles underlying mechanisms by which AREs direct rapid and selective mRNA degradation, in this study we have characterized the functionally important structural features and properties of this non-AUUUA ARE. Like AUUUA-containing AREs, this non-AUUUA ARE directs rapid shortening of the poly(A) tail as a necessary first step for mRNA degradation. It can be further dissected into three structurally and functionally distinct regions, designated domains I, II, and III. None of three domains alone is able to significantly destabilize the stable beta-globin mRNA. The two unlinked domains, I and III, together are necessary and sufficient for specifying the full destabilizing function of this non-AUUUA ARE. Domain II appears functionally dispensable but can partially substitute for domain I. Domain swaps made between the c-jun non-AUUUA and the c-fos AUUUA-containing AREs reveal that the two AREs, while sharing no sequence homology, appear to contain sequence domains that are structurally distinct but functionally overlapping and exchangeable. These data support the idea that the ultimate destabilizing function of an individual ARE is determined by its own unique combination of structurally distinct and functionally interdependent domains. Our polysome profile studies show tha the destabilizing function of the c-jun non-AUUUA ARE does not require any active transit by ribosomes of the mRNA bearing it, further corroborating that the destabilizing function of AREs is not tightly coupled to ongoing translation by ribosomes. Moreover, unlike AUUUA-containing AREs, the c-jun ARE is insensitive to blockage of its effects by addition of transcription inhibitors. Thus, our data provide further evidence for the existence of a novel class of ARE with unique properties.

The preoperative and postoperative cerebral blood flow and vasoreactivity in childhood moyamoya disease.

PURPOSE: To report the hemodynamic pattern in childhood moyamoya disease before and after vascular reconstruction. METHODS: We performed the xenon cerebral blood flow (CBF) study in 10 cases of moyamoya disease in last 3 year. In 6 of them, study before and after operation was obtained for comparison. Preoperative study was obtained in 2 cases and postoperative study was obtained in 2 cases. They were 5 males and 5 females with age ranging from 1 to 12 years old. We studied their regional CBF before and after acetazolamide (CCBF) using stable xenon computed tomography. The angiography study was obtained for comparison. RESULT: In the routine study, the CBF and CCBF were poor in the ACA and MCA territory and well correlated to the angiography finding. However, in case of basal ganglion and posterior cerebral artery involvement, xenon CBF study was more sensitive than the angiography. On the postoperative cases, the CBF could increase to a level beyond the level of CCBF shown on the preoperative study. CONCLUSION: Hemodynamic study using stable xenon computed tomography can provide an objective reference for the treatment of moyamoya disease especially in case that surgical management is considered. It is a better modality for the evaluation of surgical outcome than the conventional contrast angiography study.

Niemann-Pick disease type C (a cellular cholesterol lipidosis) treated by bone marrow transplantation.

Bone marrow transplantation (BMT) has been used for a wide variety of lysosomal storage diseases with encouraging results. We report a 3-year 5-month-old girl with Niemann-Pick type C disease (NPC) who received an allogeneic BMT. The patient presented with repeated lower respiratory tract infections, hepatosplenomegaly, failure to thrive, and developmental delay. Chest computed tomography (CT) revealed diffuse interstitial lung infiltration. Bone marrow and liver biopsies revealed abundant lipid-filled foamy macrophages. Skin fibroblast sphingomyelinase assay revealed partial deficiency. The ability of her skin fibroblasts to esterify cholesterol was very low, and the cells stained brightly for free cholesterol. She received BMT from a healthy HLA-identical male sibling donor at the age of 2 year 6 months. Full engraftment was evidenced by repeated bone marrow sex chromosome studies. Regression of the hepatosplenomegaly, markedly reduced foamy macrophage infiltration in bone marrow, and decreased interstitial lung infiltration was noted 6 months after BMT. Her neurological status, however, deteriorated. Follow-up magnetic resonance image (MRI) revealed progressive, diffuse brain atrophy. We conclude that resolution occurred in the liver, spleen, bone marrow and lung following successful engraftment. Such a response is remarkable since the underlying problem involves a membrane receptor for cholesterol. This positive response might be due to replacement of the monocyte-phagocytic system or it may imply the existence of cross-correction in the NPC membrane receptor defect by BMT approach. Since BMT did not halt the neurological deterioration, it is unlikely to be an adequate treatment for NPC.

3-D power Doppler cerebral angiography in neonates and young infants: comparison with 2-D power Doppler angiography.

The aims of this study were to evaluate the ability of 3-dimensional (3-D) power Doppler angiography (3DPDA) to depict the intracranial vasculature in infants, to compare with 2-D power Doppler ultrasonography (2DPDU), and to explore the potential clinical applications of this procedure in young infants with brain disorders. We performed 3DPDA in 27 infants. 2DPDU were completed in both sagittal and coronal directions in 12 of these patients. In the other 15, only right sagittal plane images were available for comparison. Using a grading system and with only vessels with more than half of the length demonstrated included for comparison, we compared the Doppler signals of major vessels. 3DPDA could have good visualization in more than 60% of the internal carotid artery, ophthalmic artery, pericallosal artery, callosomarginal artery, internal cerebral vein, vein of Galen, and straight sinus in the sagittal plane. 3DPDA also could have good demonstration in about 50% of basilar artery in coronal plane, and posterior communicating artery, posterior cerebral artery, and lenticulostriate artery in sagittal plane. 3DPDA was better than 2DPDU in demonstrating all the major intracranial vessels in different planes, except the anterior communicating artery. In the anterior communicating artery, neither can demonstrate more than 30%.

Early epileptic encephalopathy with suppression burst electroencephalographic pattern--an analysis of eight Taiwanese patients.

Early epileptic encephalopathy with suppression burst (SB) comprises two distinct epileptic syndromes, early infantile epileptic encephalopathy (EIEE) and early myoclonic encephalopathy (EME). We reviewed etiologies, neurological outcome and clinico-electroencephalographic features of EIEE and EME. Chart records of early epileptic encephalopathy with SB from January 1997 to December 2000 were reviewed. These cases fulfilled the diagnostic criteria of EIEE and EME. Totally eight patients (four females, four males) were enrolled. They consisted of three cases of EIEE and five cases of EME. The follow-up periods ranged from 6 to 30 months. For EIEE, two cases had migrational disorders, and one was cryptogenic; for EME, three cases had non-ketotic hyperglycinemia (NKH), one was pyridoxine dependency and one was cryptogenic. The main initial seizure patterns were tonic spasms in EIEE, and were erratic myoclonus in EME. The age of seizure onset ranged from 26 h to 5 days after birth for EIEE, and 2 h to 7 days of life for EME. The SB pattern in the electroencephalography (EEG) was noted mainly during sleep state in EME, but in both awake and sleep states in EIEE. Asymmetric SB pattern and background activities in EEG were found in migrational disorders. The EEG in all cases of EIEE changed to hypsarrhythmia at 4-6 months of age. In EME, only the EEG in cases of NKH evolved to hypsarrhythmia. Response to anti-convulsants was generally poor. All had severe psychomotor retardation. Although EIEE and EME share several common features, differences in terms of seizure seminology and evolution, EEG patterns and etiologies still exist.

Comparison of hypolipidemic effect of refined konjac meal with several common dietary fibers and their mechanisms of action.

The effects of RKM in comparison with pectin, algin and agar on lipid levels in serum and liver and on liver histopathology in rats were studied. In addition, the effects of all the tested materials on the composition and output of fecal bile acid were observed. All four kinds of dietary fiber were given at a level of 5% of diet to young male rats of Wistar strain fed on a lipid-rich diet containing 5% lard, 1% cholesterol and 0.25% cholate. All the dietary fibers tested have similar effects on serum lipid composition. In all groups, these substances prevented increases in total cholesterol in fasting serum, but the level of triglyceride was unchanged. The concentrations of total cholesterol and triglyceride in the liver were lower in the RKM group than in the control group and the other three groups. Hepatic histopathological examination also showed the most significant lipotropic effect in the RKM group. The daily output of fecal bile acids (CDCA + GDCA) was significantly increased in the four experimental groups than in the normal group and the control group. The increase of CDCA was more significant than GDCA, suggesting that the increase of fecal bile acids, especially CDCA, may be one of the mechanisms by which RKM and the other three dietary fibers exerts a hypocholesterolemic effect.

Carotenoid analysis of several dark-green leafy vegetables associated with a lower risk of cancers.

We have examined the carotenoid contents of several dark green vegetables found to be associated with a lower risk of various epithelial cancers in our epidemiological study and animal study. Samples of these vegetables were quantitatively examined by high-performance liquid chromatography (HPLC) on a C-18 reversed-phase column for individual carotenoid content. Pure reference compounds (alpha-carotene, beta-carotent, lycopene, canthaxanthin, and lutein) and internal standard (beta-Apo-8'-carotenal) were employed to quantify xanthophylls and carotenes in these vegetables. The results indicated that fresh, dark-green, leafy vegetables were high in beta-carotene (0.94-9.36 mg/100 g) and oxygenated carotenoids or xanthophylls, primarily lutein (0.94-7.39 mg/100 g), whereas lycopene and alpha-carotene were not prominent and canthaxanthin was non existent in these vegetables. These analyses suggest that consumption of carotenoids such as lutein in addition to beta-carotene may be associated with a lower risk of cancers.

Long-term animal feeding trial of the refined konjac meal. I. Effects of the refined konjac meal on the calcium and phosphorus metabolism and the bone in rat.

Effects of refined konjac meal (RKM) on the calcium and phosphorus metabolism and bone parameters were observed in rats of both sexes fed with food containing 1% of RKM for 18 months. A comparable group of rats fed on basic diet only was used as a control. Results obtained indicate that all the measured parameters (serum calcium and phosphorus level, femur weight and its calcium and phosphorus content, and the osteometry of the tibia) showed no significant difference between the experimental and the control groups. Thus there is no adverse effect either on the calcium and phosphorus metabolism or on the bone after a long-term intake at a moderate dosage.

Long-term animal feeding trial of the refined konjac meal. II. Effects of the refined konjac meal on the aging of the brain, liver, and cardiovascular tissue cells in rats.

Rats of both sexes were fed on a basal feed containing 1% refined konjac meal (RKM) for 18 months and the effects of RKM on the cell aging were observed. A comparable group fed on the basic feed was used as the control. Results obtained demonstrate that the long-term feeding of RKM to rats can delay the course of cell aging of the gliocyte, cadiomyocyte, and the endothelial cell of the large and medium arteriases, hence it is likely to delay the occurrence of arteriosclerosis and improve the functions of the brain, heart and vascular system.

The effect of foods containing refined Konjac meal on human lipid metabolism.

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

In vivo and in vitro studies on the antitumor activities of MCP (Malva crispa L. Powder).

Four short-term in vivo and in vitro tests were used to further confirm the antitumor activities of MCP, a vegetable powder, prepared from Malva crispa L. (i) In the H22 hepatoma-transplanting test, MCP had antitumor action, but MCP residue did not show such action; 5-FU appeared to have more potent antitumor activities and more harmful effects than MCP. (ii) In the micronucleus (MN) test, MCP significantly decreased MN frequency. (iii) In the cancer cell culture systems, the MCP fat-soluble extract revealed inhibitory effects on the growth and proliferation of the human hepatoma and the gastric cancer cells in a dose-response manner. (iv) In the colony formation test, MCP also altered the morphology of human gastric cancer cells. It was suggested that MCP could be consumed not only by healthy subjects for cancer prevention but also by patients with cancer as supplementary treatment in combination with anticarcinogenic drug such as 5-FU, cyclophosphamide (CP).