Outcomes after HSCT for mucolipidosis II (I-cell disease) caused by novel compound heterozygous GNPTAB mutations.

Background: Mucolipidosis type II (MLII), or I-cell disease, is a rare lysosomal storage disease (LSD) caused by variants in the GNPTAB gene. MLII patients exhibit clinical phenotypes in the prenatal or neonatal stage, such as marked dysmorphic features, cardiac involvement, respiratory symptoms, dysostosis multiplex, severe growth abnormalities, and mental and motor developmental abnormalities. The median age at diagnosis for MLII is 0.7 years, the median survival is 5.0 years, and the median age at death is 1.8 years. No cure for MLII exists. Methods: Sanger sequencing of the GNPTAB gene identified the compound heterozygous mutations c.673C > T in exon 7 and c.1090C > T in exon 9, which were novel double heterozygous mutations first reported in China. For the first time, we describe our experience in the use of HSCT for MLII. Our patient underwent HSCT with cells from a 9/10 human leukocyte antigen (HLA)-matched unrelated donor at 12 months of age. Myeloid neutrophil and platelet engraftment occurred on Days 10 and 11, respectively. Results: The patient's limb muscle tension was significantly reduced, and his gross and fine motor skills were improved four months after transplantation. DST(Developmental Screen Test) results showed that the patient's fine motor skills and mental development were improved compared with before HSCT. Conclusion: MLII is a very severe lysosomal storage disease, to date, only 3 cases have been reported on the use of HSCT to treat MLII. Our data show that HSCT is a potential way to prolong the life of patients and improve their quality of life. Due to the lack of comparable data and time, the exact benefit remains unclear in MLII patients. Longer-term follow-up and in-depth prospective studies are indispensable.

Quantitative evaluation of primary retinitis pigmentosa patients using colour Doppler flow imaging and optical coherence tomography angiography.

PURPOSE: To find the potential relation between changes in retinal large vessels and terminal vessels using colour Doppler flow imaging (CDFI) and optical coherence tomography angiography (OCTA) and to compare the respective advantages of CDFI and OCTA in evaluating vascular changes in retinitis pigmentosa (RP) patients. METHODS: A prospective series of case study was conducted to enrol RP patients and age-matched controls, who were, respectively, imaged by CDFI and OCTA. Repeatability and reproducibility of both CDFI and OCTA were performed among healthy volunteers. The central retinal artery (CRA) was detected by CDFI analysis to provide parameters of peak systolic velocity (PSV), end-diastolic velocity (EDV) and time-averaged maximum velocity (TAMV). Retinal parameters were evaluated from OCTA images, including vascular area density (VAD) of the superficial vascular layer, the fovea avascular zone (FAZ) area and retinal thickness. RP patients were separated into a high-vision group and a low-vision group, according to median vision (0.3, LogMAR 0.5). Multiple comparisons were used to analyse the data between groups. A correlation analysis was used to determine the correlation between CDFI and OCTA parameters. RESULTS: Twenty RP patients (40 eyes) and thirteen normal volunteers (26 eyes) were enrolled in this study. Repeatability and reproducibility of the measurements by CDFI had higher CVs, from 4.5% to 15.4%, than those measurements by OCTA (<5%). All the CDFI and OCTA parameters examined had significant reductions in RP patients compared to those in the controls (p < 0.01). Compared to the high-vision group, the low-vision group exhibited a statistically significant decrease in vascular parameters of the FAZ area, fovea VAD and parafovea nasal side VAD (p < 0.05); as well as in the parameters of the fovea thickness, and the parafovea nasal, superior and inferior side thickness (p < 0.05). From the correlation analysis, a significant association was found between the vision and CDFI parameters (PSV and time-averaged maximum velocity (TAMX), p < 0.05), and the vision and OCTA parameters (FAZ area, fovea and nasal side VAD, retinal thickness in all sides, p < 0.05). PSV and TAMX of the CRA were closely related to the OCTA superficial VAD in all sides, whereas the CDFI parameters showed poor correlation with retinal thickness. CONCLUSIONS: Colour Doppler flow imaging (CDFI) and OCTA parameters revealed a significant reduction in RP patients when compared to the controls. OCTA can detect vision-related microvascular and thickness changes around the macula between high- and low-vision groups, which happen earlier than the changes in large vessels. In addition to good repeatability and reproducibility, OCTA may have significant utility in the diagnosis and monitoring of disease progression in RP patients.

Repeatability and Reproducibility of Quantitative Assessment of the Retinal Microvasculature Using Optical Coherence Tomography Angiography Based on Optical Microangiography.

OBJECTIVE: The aim of this study was to determine the repeatability and reproducibility of optical coherence tomography angiography (OCTA) based on optical microangiography (OMAG) measurements of macular vessels in normal eyes. METHODS: In this prospective cohort study, 40 eyes of 40 healthy volunteers underwent repeated OCTA (Cirrus HD-OCT 5000 angiography system, Carl Zeiss Meditec, Inc.) scans on two separate visit days. On each visit day, the eyes were scanned three times. The following parameters were used to quantitatively describe the OCTA images of the superficial vascular network: vessel area density (VAD), vessel skeleton density (VSD), vessel diameter index (VDI), vessel perimeter index (VPI), vessel complexity index (VCI), flux, and foveal avascular zone (FAZ). Coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for evaluating intravisit and intervisit repeatability, as well as interobserver reproducibility. RESULTS: The measurements showed high repeatability [CVs ⪕ 4.2% (intravisit) and ⪕ 4.6% (intervisit)] and interobserver reproducibility (ICCs ⪖ 0.923) for all parameters. CONCLUSION: This study demonstrated good repeatability and reproducibility of OCTA based on OMAG for the measurement of superficial vessel parameters in normal eyes.

Coats' disease and retrobulbar haemodynamics.

PURPOSE: To study the retrobulbar haemodynamics in patients with Coats' disease. METHODS: The clinical study included 43 patients with Coats' disease. Using colour Doppler imaging, we measured the blood flow velocity in the ophthalmic artery (OA), central retinal artery (CRA) and posterior ciliary arteries (PCA), and recorded the peak systolic velocity (PSV), end diastolic velocity (EDV), time averaged maximum velocity (TAMX), pulsatility index (PI) and resistance indexes (RI). The unaffected contralateral eyes served as control group. The disease was graded into four stages. RESULTS: Compared to the contralateral eyes, the Coats' disease affected eyes showed for the CRA a significant decrease in PSV (7.08 ± 1.38 cm/s versus 8.64 ± 1.45 cm/s; p < 0.001), EDV (2.03 ± 0.41 cm/s versus 2.52 ± 0.62 cm/s; p < 0.001) and TAMX (3.67 ± 0.96 cm/s versus 4.40 ± 1.22 cm/s; p = 0.003) and for the PCA a significant decrease in PSV (9.15 ± 1.87 cm/s versus 10.14 ± 1.61 cm/s; p = 0.01). Subgroup analysis revealed that the decrease in haemodynamic parameters existed mainly in patients with stage 3A2 and stage 3B of Coats' disease. CONCLUSIONS: As measured by colour Doppler imaging, the retrobulbar blood vessels showed decreased haemodynamic parameters in patients with Coats' disease on the affected side as compared to the contralateral unaffected side, in particular in advanced stages of the disease. Future studies may address the causes and effects of these haemodynamic changes.

3D Tailored Crumpling of Block-Copolymer Lithography on Chemically Modified Graphene.

Novel 3D self-assembled nanopatterning is presented via tailored crumpling of chemically modified graphene. Block-copolymer self-assembly formed on a layer of chemically modified graphene provides highly dense and uniform 2D nanopatterns, and the controlled crumpling of the chemically modified graphene by mechanical instabilities realizes the controlled 3D transformation of the self-assembled nanopatterns.

Self-Size-Limiting Nanoscale Perforation of Graphene for Dense Heteroatom Doping.

A scalable and controllable nanoscale perforation method for graphene is developed on the basis of the two-step thermal activation of a graphene aerogel. Different resistance to the thermal oxidation between graphitic and defective domains in the weakly reduced graphene oxide is exploited for the self-limiting nanoscale perforation in the graphene basal plane via selective thermal degradation of the defective domains. The resultant nanoporous graphene with a narrow pore-size distribution addresses the long-standing challenge for the high-level doping of graphene with lattice-mismatched large-size heteroatoms (S and P). Noticeably, this novel heteroatom doping strategy is demonstrated to be highly effective for oxygen reduction reaction (ORR) catalysis. Not only the higher level of heteroatom doping but also favorable spin and charge redistribution around the pore edges leads to a strong ORR activity as supported by density functional theory calculations.

Spinal cord injury in rats treated using bone marrow mesenchymal stem-cell transplantation.

The aim of this study was to observe the effects of bone marrow mesenchymal stem-cell transplantation (BMSCs) in repairing acute spinal cord damage in rats and to examine the potential beneficial effects. 192 Wistar rats were randomized into 8 groups. Spinal cord injury was created. Behavior and limb functions were scored. Repairing effects of BMSCs transplantation was evaluated and compared. In vitro 4',6-diamidino-2-phenylindole (DAPI)-tagged BMSCs were observed, and whether they migrated to the area of spinal cord injury after intravenous tail injection was investigated. The expression of neuron-specific protein (NSE) on BMSCs was examined. Fifteen days after transplantation, the BMSCs-treated groups scored significantly higher in limb function tests than the untreated group. Pathological sections of the bone marrow after operation showed significant recovery in treated groups in comparison to the control group. After transplantation, small amounts of fluorescent-tagged BMSCs can be found in the blood vessels in the area of spinal cord injury, and fluorescent-tagged BMSCs were diffused in extravascular tissues, whereas the DAPI-tagged BMSCs could not be detected,and BrdU/NSE double-labeled cells were found in the injured marrow. BMSCs improve behavioral responses and can repair spinal cord injuries by migrating to the injured area, where they can differentiate into neurons.

Protective effects of diphenylheptanes from Curcuma phaeocaulis Val. on H2O2 induced cell injury.

Curcuma phaeocaulis Val. has been used as a health food in China for a long time. This research aimed to isolate and identify its active compounds with protective effects against hydrogen peroxide-induced PC12 cell death. 70% ethanol extracts of C. phaeocaulis were re-extracted and three fractions of water, petroleum ether and ethyl acetate were obtained. Three diphenylheptane compounds from the ethyl acetate fraction were identified for the first time from C. phaeocaulis, and compound III was considered to be a new structure. All of the three compounds displayed certain protective effects against toxicity in PC12 cells. For all concentrations, compound III displayed a more significant protective effect than ethanol extracts, the ethyl acetate fraction, and the other two compounds. At a concentration of 50 µg mL(-1), the survival rate of damaged PC-12 cells treated with compound III reached 84.7%. Diphenylheptanes were concluded to be the main compounds responsible for the health effects of C. phaeocaulis.

Molybdenum sulfide/N-doped CNT forest hybrid catalysts for high-performance hydrogen evolution reaction.

Cost effective hydrogen evolution reaction (HER) catalyst without using precious metallic elements is a crucial demand for environment-benign energy production. Molybdenum sulfide is one of the promising candidates for such purpose, particularly in acidic condition, but its catalytic performance is inherently limited by the sparse catalytic edge sites and poor electrical conductivity. We report synthesis and HER catalysis of hybrid catalysts composed of amorphous molybdenum sulfide (MoSx) layer directly bound at vertical N-doped carbon nanotube (NCNT) forest surface. Owing to the high wettability of N-doped graphitic surface and electrostatic attraction between thiomolybdate precursor anion and N-doped sites, ∼2 nm scale thick amorphous MoSx layers are specifically deposited at NCNT surface under low-temperature wet chemical process. The synergistic effect from the dense catalytic sites at amorphous MoSx surface and fluent charge transport along NCNT forest attains the excellent HER catalysis with onset overpotential as low as ∼75 mV and small potential of 110 mV for 10 mA/cm(2) current density, which is the highest HER activity of molybdenum sulfide-based catalyst ever reported thus far.

[Characteristics of choroidal melanoma in contrast-enhanced ultrasonography].

OBJECTIVE: To investigate the characteristics of choroidal melanoma in contrast-enhanced ultrasonography. METHODS: Case-control study.From October 2007 to December 2008, 21 choroidal melanoma patients (21 eyes) were treated in Beijing Tongren Hospital,including 13 males and 8 females with average age at 57 years (ranged from 18 to 76 years).Fourteen cases (14 eyes) of choroidal hemangioma treated during the same period, including 9 males and 5 females, with average age at 51 years(ranged from 24 to 71 years) were selected for the comparison.All patients were examined with contrast-enhance ultrasound, the contrast agent (sulfur hexafluoride) was injected into elbow vein,continuous recording of contrast agent in the lesions was conducted from filling to subside stages. Sonoliver software was used to analyze the imaging process.Logistic regression was used to compare the data collected from choroidal melanoma and hemangioma to develop a differential diagnosis equation for the diagnosis of choroidal melanoma. RESULTS: Contrast-enhanced ultrasonography in choroidal melanoma showed the following characteristics: the lesions were completely filled with the contrast reagent,the typical filling process began from the peripheral area to the center,filling defects were found in some cases,filling time in the melanoma was later than that in the normal tissues and faded early than that in the normal tissues. Quantitative analysis in choroidal melanoma lesions showed that the time to peak of contrast material [(22.80 ± 9.85)s] was less than that in the control group [(29.57 ± 24.76)s], maximum intensity [(191.31 ± 146.90)%] was greater than that in the control group [(100.00 ± 0.00)%]; rising time [(18.52 ± 7.09)s] was less than that in the control group [(26.45 ± 21.83)s] and mean transit time [(63.56 ± 26.04)s] was less than that in the control group [(149.87 ± 182.68)s]. The differences of maximum intensity and mean transit time between the melanoma and the controls were statistically significant (t = -2.848,2.197; P < 0.01). Logistic regression equation using the maximum intensity and mean transit time parameters could distinguish choroidal melanoma and hemangioma with a sensitivity at 90.5% (19/21) and specificity at 12/14. CONCLUSIONS: Contrast-enhanced ultrasonography is a new method for the diagnosis of malignant tumors in the eye. Contrast-enhanced ultrasonography combining with quantitative analysis can be helpful for the diagnosis and different diagnosis of choroidal melanoma.

Quantitative parameter character of choroidal melanoma in contrast-enhanced ultrasound.

BACKGROUND: Choroidal melanoma is the most common intraocular malignant tumor in adults. It threatens not only the visual function but also the patient's life. Therefore, it is important to find a non-traumatic, quantitative and repetitive diagnostic method. This study investigated the value of quantitative analysis of contrast-enhanced ultrasound (CEUS) in the diagnosis of choroidal melanoma. METHODS: CEUS were performed in 51 cases of choroidal melanoma, which were diagnosed either pathologically or clinically and in 14 cases of choroidal hemangioma. The characteristics of the time-intensity curve of the contrast agent were analyzed. For the quantitative analysis, the following parameters of the contrast agent in the lesion were included: rising time (RT), time to peak (TTP), maximum intensity (MI) and the mean transit time (MTT). RESULTS: Choroidal melanoma had the following characteristics on CEUS: Choroidal lesions were completely filled with contrast agent. The typical filling pattern was centripetal, with the peripheral of the choroidal lesion filled with the contrast agent first and then the center of the lesion. In some cases, areas with contrast agent filling defect were observed in the lesions. The contrast agent filled the lesion slower than the normal eye and orbital tissue but faded faster in the lesion. Quantitative analysis showed that in choroidal melanoma, MI of contrast agent (191.31% ± 146.90%) was significantly more than that of the normal tissue (100.00% ± 0.00%) (P < 0.05) and MTT ((63.56 ± 26.04) seconds) was significantly less than that of the normal tissue ((149.87 ± 182.68) seconds) (P < 0.05). TTP (22.80 ± 9.85) was less than that of the normal tissue ((29.57 ± 24.76) seconds) and RT ((18.52 ± 7.09) seconds) was less than that of the normal tissue ((26.45 ± 21.83) seconds). Both the differences of TTP and RT were not statistically significant though. Logistic regression showed that to predict choroidal melanoma and choroidal hemangioma with MI and MTT, the sensitivity was 90.5% and the specific degrees was 85.7%. CONCLUSIONS: CEUS is a new method to diagnose tumors in the eye. Choroidal melanoma may be diagnosed objectively and accurately by combining the graphic characteristics on CEUS and the time-intensity curve quantitative analysis.

Multidrug-resistant and extensively drug-resistant tuberculosis in multi-ethnic region, Xinjiang Uygur Autonomous Region, China.

BACKGROUND: The multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has emerged as a global threat. Xinjiang is a multi-ethnic region and suffered second highest incidence of TB in China. However, epidemiological information on MDR and XDR TB is scarcely investigated. METHODOLOGY/PRINCIPAL FINDINGS: A prospective study was conducted to analyze the prevalence of MDR and XDR TB and the differences of drug resistance TB between Chinese Han and other nationalities population at Chest Hospital of Xinjiang Uygur Autonomous Region, China. We performed in vitro drug susceptibility testing of Mycobacterium tuberculosis to first- and second-line anti-tuberculosis drugs for all 1893 culture confirmed positive TB cases that were diagnosed between June 2009 and June 2011. Totally 1117 (59.0%, 95% CI, 56.8%-61.2%) clinical isolates were resistant to ≥1 first-line drugs; the prevalence of MDR TB was 13.2% (95% CI, 11.7%-14.7%), of which, 77 (30.8%; 95% CI, 25.0%-36.6%) and 31 (12.8%; 95% CI, 8.6%-17.0%) isolates were pre-XDR and XDR TB respectively. Among the MDR/XDR TB, Chinese Han patients were significantly less likely to be younger with an odds ratio 0.42 for age 20-29 years and 0.52 for age 40-49 years; P(trend) = 0.004), and Chinese Han patients has a lower prevalence of XDR TB (9.6%) than all the other nationality (14.9%). CONCLUSIONS/SIGNIFICANCE: The burden of drug resistance TB cases is sizeable, which highlights an urgent need to reinforce the control, detection and treatment strategies for drug resistance TB. However, the difference of MDR and XDR TB between Chinese Han and other nationalities was not observed.