Five-lipoxygenase-activating protein-mediated CYLD attenuation is a candidate driver in hepatic malignant lesion.

Hepatocellular carcinoma (HCC) is an inflammation-associated cancer. However, the lipid pro-inflammatory mediators have only been seldom investigated in HCC pathogenesis. Cylindromatosis (CYLD) attenuation is involved in hepatocarcinogenesis. Here, we aimed to evaluate the significance of hepatic lipid pro-inflammatory metabolites of arachidonate-affected CYLD expression via the 5-lipoxygenase (5-LO) pathway. Resection liver tissues from HCC patients or donors were evaluated for the correlation of 5-LO/cysteinyl leukotrienes (CysLTs) signaling to the expression of CYLD. The impact of functional components in 5-LO/CysLTs cascade on survival of HCC patients was subsequently assessed. Both livers from canines, a preponderant animal for cancer research, and genetic-modified human HCC cells treated with hepatocarcinogen aristolochic acid I (AAI) were further used to reveal the possible relevance between 5-LO pathway activation and CYLD suppression. Five-LO-activating protein (FLAP), an essential partner of 5-LO, was significantly overexpressed and was parallel to CYLD depression, CD34 neovascular localization, and high Ki-67 expression in the resection tissues from HCC patients. Importantly, high hepatic FLAP transcription markedly shortened the median survival time of HCC patients after surgical resection. In the livers of AAI-treated canines, FLAP overexpression was parallel to enhanced CysLTs contents and the simultaneous attenuation of CYLD. Moreover, knock-in FLAP significantly diminished the expression of CYLD in AAI-treated human HCC cells. In summary, the hepatic FLAP/CysLTs axis is a crucial suppressor of CYLD in HCC pathogenesis, which highlights a novel mechanism in hepatocarcinogenesis and progression. FLAP therefore can be explored for the early HCC detection and a target of anti-HCC therapy.

Safety and immunogenicity of hepatitis E vaccine in elderly people older than 65 years.

BACKGROUND: Hepatitis E virus (HEV) infection is a leading cause of acute hepatitis worldwide, and results in high morbidity and mortality rates among elderly people in China. The hepatitis E vaccine, Hecolin®, has been shown to be safe and highly efficacious among healthy adults aged 16-65 years old. However, there is no data about Hecolin® vaccination in elderly people older than 65 years (y). METHODS: An open-labeled, controlled trial was conducted to evaluate the safety and immunogenicity of Hecolin® among the elderly aged >65 y. A total of 601 eligible participants were enrolled. Among them, 200 elderly people aged >65 y and 201 adults aged 18-65 y were assigned to the Hecolin® groups and vaccinated at day 0, month 1 and month 6. Serum samples were collected for anti-HEV IgG determination at day 0 prior to immunization and at month 7. The remaining 200 elderly people aged >65 y were assigned to the safety control group and received no intervention but were instructed to report any adverse events that occurred during the whole study period in the same way as those in the Hecolin® groups. RESULTS: After receiving 3 doses of Hecolin® with the standard schedule, most (96.7%) of the vaccinated elderly people aged >65 y seroconverted at one month after the final dose (month 7). At month 7, the geometric mean concentrations of anti-HEV IgG were 5.36 (95% CI, 3.88-7.41) and 19.65 (95% CI, 16.81-22.98) among the baseline seronegative and seropositive elderly, respectively. Of the vaccinated elderly, 97.3% (177/182) had anti-HEV IgG levels higher than 1.0 WU/ml at month 7. Hecolin® was very well tolerated in this population. No vaccine-related SAEs were reported. CONCLUSIONS: Hecolin® is immunogenic and well tolerated in elderly people aged greater than 65 years.

Psycho-behavioral changes in children with type 1 diabetes mellitus.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is the most common type of diabetes in children. This study aimed to investigate psycho-behavioral changes in Chinese children with T1DM and to provide some advices for nurses, parents and other persons. METHODS: Forty-five patients with T1DM (26 boys and 19 girls with a mean age of 10.40±3.01 years) were enrolled. According to the glycosylated hemoglobin levels recommended by the American Diabetes Association, the patients were subdivided into a well-controlled group and a poorly-controlled group. Fifty-three healthy children served as a control group. Psycho-behavioral changes were investigated by using Achenbach's Child Behavior Check List. RESULTS: Compared with the control group, the patients with T1DM had significantly higher mean scores for withdrawal, anxiety/depression, attention problems, delinquent behavior, aggressive behavior, externalizing problems, and internalizing problems (P<0.017). Moreover, the mean scores for somatic complaints in the poorly-controlled subgroup were significantly higher than those in the well-controlled subgroup (t=3.582, P=0.001). Compared with the control group, the well-controlled subgroup had higher scores for withdrawal, anxiety/depression, and internalizing problems (P<0.017). But the poorly-controlled subgroup had higher scores for withdrawal, somatic complaint, anxiety/depression, delinquent behavior, aggressive behavior, externalizing and internalizing problems (P<0.017). CONCLUSIONS: Children with T1DM may have some psycho-behavioral problems. Timely nursing interventions must be conducted to solve these problems.

Paragonimiasis in chinese children: 58 cases analysis.

OBJECTIVE: To analyze the clinical and radiological features of paragonimiasis in children and raise the awareness of this disease. METHODS: A total of 58 paragonimiasis patients were reviewed. They were 42 boys and 16 girls aged 2.0 to 15.3 years. FINDINGS: Among these patients, 20 were diagnosed in the recent 5 years, 46 with a history of raw water or food ingestion. Except 2 patients without any complaint, the most common features involved the systemic (41, 70.7%) and respiratory systems (43, 74.1%), followed by abdominal, cardiac and nervous systems, with rash and mass. Eosinophilia was noted in 46 (79.3%) patients, granulocytosis in 45 (77.6%), anemia in 14 (24.1%), and thrombocytopenia in 3. Imageology showed pneumonia in 26 (44.8%) patients, pleurisy in 28 (48.3%), hydropericardium in 17 (29.3%), ascites in 16 (27.6%), and celiac lymphadenitis in 13 (22.4%). Besides hepatomegaly and splenomegaly, calcification and multiple lamellar low echogenic areas in the liver were noted, each in one patient. Abnormal brain imaging was noted in 4 of 10 patients. Karyocyte hyperplasia with eosinophilia was noted in all the 19 patients who received bone marrow puncture. CONCLUSION: Paragonimiasis should be considered in the differential diagnosis of patients with multiple organs or system lesions, especially those with eosinophilia, serous cavity effusion, respiratory, cardiac, digestive system, nervous system abnormality, and/or mass. Healthy eating habit is helpful for paragonimiasis prevention.

Thymine-protected gold nanoparticles: assembly and disassembly of gold nanoparticles in the presence of Hg2+.

In this paper, we describe thymine-protected gold nanoparticles. Assembly of thymine-protected gold nanoparticles into interconnected network was observed by gradual addition of Hg2+. Moreover, the plasmon absorption intensity varied almost linearly with the concentration of Hg2+, indicating that thymine-protected gold nanoparticles are potentially useful for signaling Hg2+. It is interesting to note that disassembly of gold nanoparticles occurred when the concentration of Hg2+ in the solution was high. It is proposed that the assembly of gold nanoparticles is due to the coordination of Hg2+ with thymine groups of adjacent nanoparticles, while the disassembly of gold nanoparticles is attributed to the electrostatic repulsion among the nanoparticles with positive charges which are generated through the coordination of Hg2+ with thymine groups absorbed on the surface of each nanoparticle.

[The measurement of central corneal thickness of normal subjects and glaucomatous patients with optical coherence tomography].

OBJECTIVE: To evaluate central corneal thickness (CCT) of normal subjects, patients with primary open angle glaucoma (POAG), normal tension glaucoma (NTG) and ocular hypertension (OHT) using optical coherence tomography (OCT). METHODS: One hundred and forty-three eyes of 143 normal subjects, 36 eyes of 36 patients with POAG, 39 eyes of 39 patients with NTG and 40 eyes of 40 patients with OHT were enrolled. CCT were measured by OCT3 and analyzed using ANOVA. The relationship of CCT and intraocular pressure (IOP) measured by Goldmann applanation tonometry were analyzed by linear regression. The inter-observer and intra-observer agreement of CCT measurement by OCT were analyzed by interclass correlation coefficient (ICC). RESULTS: The average CCT of normal subjects, patients with POAG, NTG and OHT were (525.31 +/- 32.18) microm, (531.87 +/- 31.58) microm, (507.61 +/- 21.56) microm and (574.09 +/- 27.84) microm, respectively. There was no significant difference between normal subjects and patients with POAG (P = 0.099). The average CCT of OHT patients was larger than those of other groups (P < 0.001). The average CCT of patients with NTG was less than those of other groups (P < 0.001). There was positive relationship between CCT and IOP in normal subjects (r = 0.318, R2 = 0.101, P < 0.001). The ICC of inter-observer and intra-observer agreement of CCT measurement by OCT were 0.995 and 0.996 respectively. CONCLUSIONS: Central corneal thickness could be measured by OCT accurately. The average CCT in the patients with NTG was thinner, but the average CCT in the patients with OHT was thicker than that of normal subjects. CCT could affect IOP measurement in the application of Goldmann applanation tonometry but with little significant.

[Analysis of topograph and relevant factors of optic nerve head in normal subjects].

OBJECTIVE: To study the optic nerve head (ONH) parameters and topograph features of normal subjects, and analyze the effect of gender, laterality, age and disc size on the topograph of ONH. METHODS: Heidelberg Retina Tomograph (HRT) was used to obtain the optic nerve head parameters and topograph images in 216 eyes of 116 normal volunteers. The impact of gender, laterality, age and disc size on the topograph was analyzed. The optic disc was divided into three groups by their size, small (less than 1.5 mm2), middle and large disc (equal or larger than 2.5 mm2), to evaluate the differences of parameters. RESULTS: The parameters of ONH in normal eyes were as following: disc area (DA) (2.208 +/- 0.411) mm, cup area (CA) (0.466 +/- 0.355) mm2, cup/disk area ratio (C/DAR) (0.217 +/- 0.137), rim area (RA) (1.563 +/- 0.339) mm2, height variation contour (HVC) (0.404 +/- 0.096) mm, cup volume (CV) 0.127 mm3, rim volume (RV) (0.446 +/- 0.173) mm3, mean cup depth (MCD) (0.196 +/- 0.096) mm, maximum cup depth (MxCD) (0.559 +/- 0.228) mm, cup shape measure (CSM) (-0.213 +/- 0.076), mean retinal nerve fiber layer thickness (mRNFLT) (0.272 +/- 0.076) mm, and retinal nerve fiber layer cross section area (RNFLA) (1.364 +/- 0.375) mm2. There were significant differences between right and left eyes in C/DAR, RA and RV, but no difference between different genders in all parameters. A negative correlation was found between mRNFLT, RNFLA and age. There were significant differences in most parameters among three groups with different disc size, such as CA, C/DAR, CV, RA and CSM, but not in mRNFLT, RNFLA and RV. CONCLUSIONS: Significant variations were found in parameters of ONH in normal subjects. Some parameters of ONH were affected by age and optic disc size. There were differences in some parameters between right and left eyes, but not between different genders. There were differences of parameters between different quadrants of ONH.

[The diagnostic ability of Heidelberg retina tomography to detect glaucomatous optic neuropathy in Chinese].

OBJECTIVE: To evaluate the ability of Heidelberg retina tomography (HRT) in the diagnosis of primary open angle glaucoma (POAG). METHODS: The topography of optic nerve head of 116 normal eyes and 99 eyes with POAG were examined using HRT. The differences of the optic disc parameters between two groups were compared. The topographic parameters of the optic nerve head were undergone stepwised discriminant analysis and the discriminant function was established. The sensitive diagnostic parameters of POAG were screened. RESULTS: The topographic parameters of optic nerve head, including disc area (DA), cup area (CA), cup/disc area ratio (C/DAR), rim area (RA), height variation contour (HVC), cup volume (CV), rim volume (RV), mean cup depth (MCD), maximum cup depth (MxCD), cup shape measure (CSM), mean retinal nerve fiber layer thickness (mRNFLT), retinal nerve fiber layer cross section area (RNFLA), showed significant (P < 0.001) difference between normal subjects and patients with POAG. The sensitive diagnostic parameters of POAG were C/DAR, RA, CSM, CV, MCD. The discriminant function was Y = -2.083-4.833 x C/DAR-20.379 x CSM + 2.035 x RA + 3.955 x CV-3.701 x MxCD. The sensitivity, specificity and diagnostic accuracy were 81.8%, 86.2% and 84.2%, respectively, which were comparable to the automatic analysis program of HRT. CONCLUSIONS: The topographic parameters of optic nerve head in patients with POAG showed significant differences from that in normal people. The power of discriminant function established based on our data was comparable to the HRT automatic analysis program. Our results indicate that HRT automatic analysis program is applicable to Chinese.

[Study of agreement of optic nerve head topography parameters].

OBJECTIVE: To evaluate the interobserver and intraobserver agreement of parameters of optic nerve head by Heidelberg Retina Tomograph (HRT). METHODS: Optic nerve heads from 50 eyes (30 subjects) were imaged with the HRT. Three ophthalmologists majoring in glaucoma traced the disc margin with a contour line. One of these observers, repeatedly traced the disc margin with contour line in triplicate at three different times. Eleven topographic parameters of optic nerve head (including disc area, cup area, cup/disc area ratio, rim area, cup volume, rim volume, mean cup depth, maximum cup depth, cup shape measure, mean retinal nerve fiber layer thickness, sectional area of retinal nerve fiber layer) were analyzed with HRT software (version 2.01). Intraclass coefficients (ICC) and agreement of result estimation (kappa value) were calculated. RESULTS: The ICCs results among three observers on 12 parameters of optic nerve head topography were 0.976 - 0.999, which showed almost perfect agreement; and the kappa value were 0.649 approximately 0.767, which showed substantial agreement. The ICC of the same observer in different times were 0.983 approximately 0.999, which showed almost perfect agreement; and the Kappa values were 0.810 approximately 0.951, which showed substantial agreement. CONCLUSIONS: Tracing the optic nerve head with contour line on HRT image is substantial to almost perfect within both interobserver and intraobserver in experienced ophthalmologist. This procedure is suitable for clinical diagnosis and follow-up observation of glaucoma.