Host-derived oxidized phospholipids initiate effector-triggered immunity fostering lethality upon microbial encounter.

Macrophages detect invading microorganisms via pattern recognition receptors that recognize pathogen-associated molecular patterns, or via sensing the activity of virulence factors that initiates effector-triggered immunity (ETI). Tissue damage that follows pathogen encounter leads to the release of host-derived factors that participate to inflammation. How these self-derived molecules are sensed by macrophages and their impact on immunity remain poorly understood. Here we demonstrate that, in mice and humans, host-derived oxidized phospholipids (oxPLs) are formed upon microbial encounter. oxPL blockade restricts inflammation and prevents the death of the host, without affecting pathogen burden. Mechanistically, oxPLs bind and inhibit AKT, a master regulator of immunity and metabolism. AKT inhibition potentiates the methionine cycle, and epigenetically dampens Il10, a pluripotent anti-inflammatory cytokine. Overall, we found that host-derived inflammatory cues act as "self" virulence factors that initiate ETI and that their activity can be targeted to protect the host against excessive inflammation upon microbial encounter.

[Cautious about the indication expansion of intraocular refractive surgery].

Myopic refractive surgery has developed vigorously in China during the past 30 years, and the number of surgeries is increasing year by year. Since intraocular refractive surgery has a wide range of correction, no need to cut the corneal tissue and a stable visual quality, it has been gradually promoted in clinical practice. Specialists from the Optometry Group of Chinese Ophthalmological Society have given guidance on the ocular indications, age, diopters and other aspects for the posterior chamber intraocular lens implantation. In this article, the authors expound that intraocular refractive surgery should not be recommended for low and moderate myopic eyes, neither for some special occupations at present. The complications of intraocular refractive surgery and the countermeasures are also discussed. The authors also put forward the principles of customized myopic refractive surgery and emphasize that the clinicians should be more cautious about the diopter range selection, occupational need evaluation, individual differences and complications of intraocular refractive surgery. (Chin J Ophthalmol, 2020, 56: 89-92).

Excessive Oxidative Stress in the Synergistic Effects of Shikonin on the Hyperthermia-Induced Apoptosis.

BACKGROUND: Hyperthermia (HT) has been used widely for cancer therapy, and the development of modern devices has made it more efficient. Shikonin (SHK) is a natural naphthoquinone derivative from a Chinese herb. Although the anticancer properties of SHK are evident, the underlying molecular mechanisms are not fully understood. OBJECTIVE: In this study, the effects of combining low doses of SHK with mild HT were investigated in the U937 cell line. METHODS: The cells were subjected to HT at 44°C for 10 min with or without SHK pretreatment, and parameters reflecting apoptosis, ROS generation and intracellular calcium elevation were evaluated by using DNA fragmentation, flow cytometry, and western blot analyses. RESULTS: SHK 0.5 µM significantly enhanced HT-induced apoptosis as indicated by DNA fragmentation and caspase-3 activation with increased generation of ROS and elevation of intracellular calcium. The combined treatment also synergistically activated proapoptotic proteins and inactivated anti-apoptotic proteins. Furthermore, the phosphorylation of JNK and PKC- δ and the dephosphorylation of ERK and AKT were the upstream effects that may have compounded the induction of apoptosis. The modulatory effects of HT and SHK were abrogated with the employment of NAC and JNK-IN-8 by inactivating the MAPK pathway and cleavage of caspase-3. Intracellular calcium was also elevated and was found to be responsible for the induction of cell death evident by the DNA fragmentation with or without the employment of BAPTA-AM. CONCLUSION: Conclusively, this study provides persuasive evidence that SHK in combination with HT is a propitious therapeutic way for augmentation of apoptosis and hence suggest a novel strategy for treating cancers.

[The vitamin D nutritional status in Chinese urban women of child-bearing age from 2010 to 2012].

Objective: To evaluate the vitamin D nutritional status in Chinese women of child-bearing age by analyzing serum 25-hydroxyvitamin D level in 2010-2012. Methods: Data were obtained from the China Nutrition and Health Survey in 2010-2012. Using cluster sampling and proportional stratified random sampling, 1 514 women of child-bearing age (18-44 years old) from 34 metropolis and 41 small and medium-sized cities were included in this study. Demographic information was collected by questionnaire and serum 25-hydroxyvitamin D concentration was determined by radioimmunoassay, in accordance with the 2010 Institute of Medicine of the National Academies standards. We compared differences in vitamin D levels, specifically serious deficiency, lack of deficiency, insufficiency, and excess. Results: The overall serum 25-hydroxyvitamin D level of Chinese urban women of child-bearing age (P(50) (P(25)-P(75))) was 20.1 (15.1-26.3) ng/ml; minorities had a significantly higher serum 25-hydroxyvitamin D level of 22.0 (15.9-27.5) ng/ml compared with women of Han nationality (19.8 (14.9-26.2) ng/ml) (χ(2)=7.02, P=0.008). The proportions of women with serious deficiency, lack of deficiency, insufficiency, and excess vitamin D were 11.6% (n=175), 37.9% (n=574), 35.1% (n=531), and 0.3% (n=5), respectively. Only 15.1% (n=229) of women of child-bearing age had normal vitamin D nutritional status. No significant differences in vitamin D nutritional status were observed according to age, body mass index, city, nationality, educational level, marital status, or household income per capita (P>0.05). Conclusion: Most Chinese urban women of child-bearing age have poor vitamin D levels and require vitamin D supplementation.

[Study on vitamin A nutritional status of 6- to 17-year-old urban children and adolescents between 2010 and 2012 in China].

Objective: To investigate the vitamin A nutritional status of 6- to 17-year-old urban children and adolescents by analyzing serum retinol level, between 2010 and 2012 in China. Methods: Data were obtained from the China Nutrition and Health Survey in 2010-2012. Using multi-stage stratified sampling and the population proportional stratified random sampling method, 6 617 children aged 6-17 years from 32 metropolis and 41 middle-sized and small cities of China were selected. The questionnaire survey was used to collect demographic information. Blood samples were analyzed using high-performance liquid chromatography to determine serum retinol concentration, and the World Health Organization guidelines were used to evaluate the nutritional status of vitamin A. Vitamin A levels, vitamin A deficiency, and marginal vitamin A deficiency in children with different characteristics were compared. Results: A total of 3 785 cases with valid samples were obtained. The overall mean serum retinol concentration level was (1.49±0.71) µmol/L; the mean serum retinol concentration was (1.55±0.69) µmol/L for metropolis and (1.49±0.75) µmol/L for middle-sized and small cities (P>0.05). The mean serum retinol concentration was (1.52±0.78) µmol/L for boys and (1.47±0.68) µmol/L for girls (P>0.05). The mean serum retinol concentration level was (1.46±0.70) µmol/L for 6- to 11-year-old children and (1.54±0.65) µmol/L for 12- to 17-year-old children (P<0.05). The total vitamin A deficiency rate and marginal vitamin A deficiency rate was 7.69% (291/3 785) and 18.57% (703/3 785), respectively. The vitamin A deficiency rate was 8.00% (36/450) for metropolis and 7.64% (65/3 335) for middle-sized and small cities; 8.12% (155/1 908) for boys and 7.25% (136/1 877) for girls; and 8.04% (171/2 115) for 6- to 11-year-old children and 7.18% (120/1 670) for 12- to 17-year-old children. No significant differences were observed for region, sex, or age (P>0.05). The marginal vitamin A deficiency rate was 19.11% (86/450) for metropolis and 18.50% (617/3 335) for middle-sized and small cities; 18.19% (347/1 908) for boys and 18.97% (356/1 877) for girls, with no significant differences observed (P>0.05). The marginal vitamin A deficiency rate was 16.54% (350/2 115) for 6- to 11-year-old children and 21.13% (353/1 670) for 12- to 17-year-old children (P<0.05). Conclusion: The vitamin A nutritional status of 6- to 17-year-old Chinese urban children and adolescents between 2010 and 2012 has improved, and the gap between cities is narrowing. However, vitamin A deficiency overall remains high, especially in younger children, and requires specific attention.

[HBXIP expression in gastric adenocarcinoma predicts poor prognosis].

Objective: To investigate the localization of HBXIP protein over-expression in gastric adenocarcinoma, and its prognostic significance. Methods: HBXIP localization was detected by immunofluorescence in AGS gastric cancer cell line, and by immunohistochemical staining in 97 gastric adenocarcinomas, 41 adjacent non-tumor tissues and 13 gastric adenoma tissues. Correlation between HBXIP expression and clinicopathological features of gastric cancer patients was evaluated by Chi-square and Fisher's exact tests. Overall survival rates were calculated using Kaplan-Meier method. Results: HBXIP was mainly expressed in the cytoplasm of gastric cancer. The positive and strongly positive expression rates of HBXIP protein in gastric cancers were 68.0% (66/97) and 49.5% (48/97) respectively, and were significantly higher than those in adjacent non-tumor tissues(48.8%, 20/41; 36.6%, 15/41) or gastric adenomas(2/13, 1/13; all P<0.05). HBXIP expression correlated significantly with tumor differentiation and lymph node status (P=0.007; 0.041). Kaplan-Meier survival analysis showed that the overall survival rate was significantly lower in gastric cancer patients with high HBXIP expression (P=0.015). Conclusions: HBXIP expression in gastric cancer is mainly expressed in cytoplasmic, and the expression level is closely related to the prognosis. HBXIP expression status may potentially be used as an important prognostic indicator for gastric cancer.

MELD and Child-Pugh Scores Are Related to Immune Status of Intrahepatic Natural Killer Cells in Liver Transplant Candidates.

BACKGROUND: The role and phenotypic alterations of intrahepatic natural killer (NK) cells in liver disease were investigated. Although intrahepatic NK cells reportedly functionally deteriorate in the fibrotic liver, it remains unclear how the clinical severity of liver disease affects intrahepatic NK cells in patients with advanced liver failure. METHODS: We analyzed the phenotypic properties of intrahepatic NK cells by using mononuclear cells extracted from ex vivo liver perfusate effluents from patients who underwent liver transplantation. The relationship between the clinical severity of liver disease and the phenotype of intrahepatic NK cells in these patients was also evaluated. To estimate the immunological responsiveness of intrahepatic NK cells, phenotypic enhancement after interleukin-2 stimulation was analyzed. RESULTS: Intrahepatic NK cells from patients with advanced liver failure exhibited down-regulated monomodal expression of NKp46, a major activating molecule. Notably, the expression level of NKp46 decreased depending on the severity of liver disease, Model for End-Stage Liver Disease score, and Child-Pugh score rather than the etiology. After in vitro recombinant interleukin-2 stimulation, the enhancement of expression of cytotoxic molecules, NKp44, and tumor necrosis factor-related apoptosis-inducing ligand was significantly impaired in intrahepatic NK cells from patients with liver failure, concurrently with decreased expression of CD122 and interleukin-2 receptor beta. CONCLUSIONS: Our results suggest that terminal deterioration of liver environments by chronic liver disease impairs the potential of local NK cells, depending on the severity of the deterioration. These influences of advanced liver failure on intrahepatic NK cells may be attributed to multicentric carcinogenesis in patients with liver failure.

Assessment of selenium nutritional status of school-age children from rural areas of China in 2002 and 2012.

BACKGROUND/OBJECTIVES: To assess the selenium nutritional status of 3458 school-age children recruited from rural areas using the China Nutrition and Health Survey 2002 and 2012 (CNHS 2002 and CNHS 2012). SUBJECTS/METHODS: The serum selenium concentration was determined by high-resolution inductively coupled plasma mass spectrometry. The prevalence of dietary selenium intake insufficiency was calculated according to the formula suggested by and the estimated average requirements of the new Chinese Dietary Reference Intakes. The percentage of low selenium was based on the cutoff values with a serum selenium concentration below the threshold limit of clinical importance in coronary and cardiovascular diseases (<45 µg/l) and in abnormal physiological functions (<60 µg/l). RESULTS: The overall median serum selenium concentration was 64.3 µg/l in the CNHS 2002 and 74.2 µg/l in the CNHS 2012. The median calculated dietary selenium intake was 26.7 µg/day in the CNHS 2002 and 33.2 µg/day in the CNHS 2012 together with a 61.1% and 52.8% dietary selenium intake insufficiency in the CNHS 2002 and in the CNHS 2012. In addition, the percentages of low selenium (<45 µg/l and <60 µg/l) were 25.1 and 43.8% in the CNHS 2002 but 9.4 and 25.6% in the CHNS 2012. CONCLUSIONS: The selenium nutritional status of school-age children was significantly improved in the CNHS 2012 versus the CNHS 2002. However, the health risk for selenium malnutrition in school-age children remains a potential problem affecting children's health.

HPV16 E6 mutations and p53 codon72 polymorphism among women with cervical intraepithelial neoplasia 2 and 3 in China.

OBJECTIVE: To study the distribution of HPV16 E6 gene mutations and p53 codon72 polymorphism among women with HPV16+ cervical precancerous lesions and explore their relationship with the risk of cervical intraepithelial neoplasia (CIN) 2, 3. Materials and Meth- ods: This study analyzed a total of 112 cases of exfoliated HPV16+ cervical cell specimens which were divided into group I (normal and CIN1, 55 cases) and group2 (CIN2, 3, 57 cases). Among the 112 specimens, 85 cases were successfully amplified for HPV E6 gene by PCR and the PCR products were sequenced directly. P53 codon72 region was also amplified from the 112 specimens and the PCR products were sequenced directly and compared with the standard sequence. RESULTS: Among the 85 amplified HPV sequences, point mutations such as T178G, T350G, G132A, A442C, T310G, G94T, C551A, etc. were found, among which, T178G showed the highest rate (51.76%). The rate of HPV16 E6 mutation T178G in CIN2, 3 group was significantly higher than that in normal and CINI group, i.e., in the 112 amplified p53 codon72 sequences, the distribution of Pro/Pro genotype in normal, and CIN1 group was significantly different from that in CIN2, 3 groups, and the disease risk of Pro/Pro genotype was much higher than that of Arg/Arg and Arg/Pro genotypes. CONCLUSION: HPV16 E6 T178G mutation increases the disease risk of CIN2, 3. Meanwhile, compared with Arg/Arg and Arg/Pro genotypes, p53 codon72 Pro/Pro genotype more associated with the disease risk of CIN2, 3.

Replication of results of genome-wide association studies on esophageal squamous cell carcinoma susceptibility loci in a Korean population.

Two recent genome-wide association studies have identified that the rs2274223 single-nucleotide polymorphism inphospholipase C epsilon 1 and the single-nucleotide polymorphism rs13042395 in C20orf54 are involved in esophageal squamous cell carcinoma (ESCC) in Chinese populations. We hypothesized that genetic polymorphisms of phospholipase C epsilon 1 and C20orf54 are also associated with ESCC in a Korean population. The rs2274223 and rs13042395 genotyping was performed using high-resolution melting analysis. The rs2274223 GG genotype was significantly associated with an increased risk of ESCC (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.08-3.25) compared with the rs2274223 AA genotype. The rs13042395 G allele showed a significantly decreased risk of ESCC in the younger age group (OR=0.71, 95% CI=0.52-0.97) and no significant association in the older group (OR=1.19, 95% CI=0.87-1.62). We observed that the rs2274223 polymorphism was associated with an increased risk of ESCC in this Korean case-control study and that age may modify the association between the rs13042395 polymorphism and the risk of ESCC.

p53 codon 72 polymorphism and the risk of esophageal cancer: a Korean case-control study.

The aim of this study was to assess whether p53 codon 72 polymorphism is associated with an increased risk of esophageal cancer (EC) in South Korea. We conducted a case-control study including 340 patients with EC, and 1700 controls. P53 codon 72 polymorphism was determined by real-time polymerase chain reaction. The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in EC were 39.4%, 45.6%, and 15.0%, respectively; frequencies in the controls were 43.2%, 45.6%, and 11.2%, respectively. Compared with the Arg/Arg genotype, the OR of the Arg/Pro genotype was 1.09 (95% CI = 0.85-1.41) and that of the Pro/Pro genotype was 1.47 (95% CI = 1.02-2.11) for EC overall. When adjusted by age, gender, and smoking status, the OR of the Arg/Pro genotype was 1.24 (95% CI = 0.92-1.67) and that of the Pro/Pro genotype was 1.77 (95% CI = 1.15-2.74) for EC overall. In never-smokers and ever-smokers, the OR of the Arg/Pro genotype was 0.59 (95% CI = 0.37-0.95) and 1.39 (95% CI = 1.00-1.91), respectively, and there was a significant difference in the homogeneity test (P= 0.011). We observed that the p53 codon 72 polymorphism was associated with an increased risk of EC in this Korean case-control study, and smoking status modified the association between the p53 codon 72 polymorphism and the risk of EC.

Partial volume effect correction in PET using regularized iterative deconvolution with variance control based on local topology.

Correcting positron emission tomography (PET) images for the partial volume effect (PVE) due to the limited resolution of PET has been a long-standing challenge. Various approaches including incorporation of the system response function in the reconstruction have been previously tested. We present a post-reconstruction PVE correction based on iterative deconvolution using a 3D maximum likelihood expectation-maximization (MLEM) algorithm. To achieve convergence we used a one step late (OSL) regularization procedure based on the assumption of local monotonic behavior of the PET signal following Alenius et al. This technique was further modified to selectively control variance depending on the local topology of the PET image. No prior 'anatomic' information is needed in this approach. An estimate of the noise properties of the image is used instead. The procedure was tested for symmetric and isotropic deconvolution functions with Gaussian shape and full width at half-maximum (FWHM) ranging from 6.31 mm to infinity. The method was applied to simulated and experimental scans of the NEMA NU 2 image quality phantom with the GE Discovery LS PET/CT scanner. The phantom contained uniform activity spheres with diameters ranging from 1 cm to 3.7 cm within uniform background. The optimal sphere activity to variance ratio was obtained when the deconvolution function was replaced by a step function few voxels wide. In this case, the deconvolution method converged in approximately 3-5 iterations for most points on both the simulated and experimental images. For the 1 cm diameter sphere, the contrast recovery improved from 12% to 36% in the simulated and from 21% to 55% in the experimental data. Recovery coefficients between 80% and 120% were obtained for all larger spheres, except for the 13 mm diameter sphere in the simulated scan (68%). No increase in variance was observed except for a few voxels neighboring strong activity gradients and inside the largest spheres. Testing the method for patient images increased the visibility of small lesions in non-uniform background and preserved the overall image quality. Regularized iterative deconvolution with variance control based on the local properties of the PET image and on estimated image noise is a promising approach for partial volume effect corrections in PET.

Childhood obesity and its health consequence in China.

Analyses of data from the representative 2002 National Nutrition and Health Survey were used to assess the likelihood of metabolic complications of overweight and obesity in Chinese children aged 7-17 years. Chinese criteria for body mass index classification were used for overweight and obesity with the 75th percentile US adolescent values for waist circumferences and all the metabolic criteria for blood pressure, lipids, fasting glucose established for US adolescents. Diabetes in 7-12-year-olds was 0.2% and 0.4% in children aged 12-18 years. Prevalences of dyslipidaemia (61.9%), hypertriglyceridaemia (18.2%) and low high-density lipoprotein cholesterol (56.1%) were high and 16.0% of 15-18 years had hypertension. The overall prevalence of the metabolic syndrome was 3.3% with more than half the children having at least one metabolic abnormality and 19.8% having at least two. All the metabolic parameters were significantly elevated in the overweight and obese children except high-density lipoprotein cholesterol. These data emphasize the marked sensitivity of Chinese children to the metabolic complications of overweight and obesity and amplify the need for early preventive measures.

Prevalence of the metabolic syndrome in Chinese adolescents.

Since national figures on the occurrence of metabolic syndrome among Chinese adolescents are lacking, this study aims to estimate its prevalence and distribution among Chinese youngsters. The 2002 China National Nutrition and Health Survey is a nationally representative cross-sectional study. Applying the criteria for US adolescents, we estimated the prevalence of metabolic syndrome among 2761 adolescents aged 15 to 19 years. The prevalence of metabolic syndrome among Chinese adolescents overall was 3.7 % (10 % in US adolescents). It was 35.2 %, 23.4 % and 2.3 % among adolescents who were overweight (BMI > or = 95th percentile), at risk of overweight (BMI between 85th and 95th percentile) and normal weight (BMI below the 85th percentile), respectively. Urban boys had the highest rate (5.8 %) compared with girls and rural youngsters. Among adolescents who had a BMI > or = 85th percentile and one or two parent(s) with metabolic syndrome, the prevalence was 46.4 %. A total of 96 % of overweight adolescents had at least one and 74.1 % overweight adolescents had at least two abnormalities of metabolic syndrome. Based on these figures, it is estimated that more than three million Chinese adolescents have metabolic syndrome. Both overweight and metabolic syndrome prevalence among adolescents are still relatively low in China, but the prevalence of metabolic syndrome among Chinese overweight adolescents is similar to those living in the USA.

Reactive oxygen species mediate crosstalk between NF-kappaB and JNK.

The activation of NF-kappaB inhibits apoptosis via a mechanism involving upregulation of various antiapoptotic genes, such as cellular FLICE-inhibitory protein (c-FLIP), Bcl-xL, A1/Bfl-1, and X chromosome-liked inhibitor of apoptosis (XIAP). In contrast, the activation of c-Jun N-terminal kinase (JNK) promotes apoptosis in a manner that is dependent on the cell type and the context of the stimulus. Recent studies have indicated that one of the antiapoptotic functions of NF-kappaB is to downregulate JNK activation. Further studies have also revealed that NF-kappaB inhibits JNK activation by suppressing accumulation of reactive oxygen species (ROS). In this review, we will focus on the signaling crosstalk between the NF-kappaB and JNK cascades via ROS.

The three-dimensional scintillation dosimetry method: test for a 106Ru eye plaque applicator.

The need for fast, accurate and high resolution dosimetric quality assurance in radiation therapy has been outpacing the development of new and improved 2D and 3D dosimetry techniques. This paper summarizes the efforts to create a novel and potentially very fast, 3D dosimetry method based on the observation of scintillation light from an irradiated liquid scintillator volume serving simultaneously as a phantom material and as a dose detector medium. The method, named three-dimensional scintillation dosimetry (3DSD), uses visible light images of the liquid scintillator volume at multiple angles and applies a tomographic algorithm to a series of these images to reconstruct the scintillation light emission density in each voxel of the volume. It is based on the hypothesis that with careful design and data processing, one can achieve acceptable proportionality between the local light emission density and the locally absorbed dose. The method is applied to a Ru-106 eye plaque immersed in a 16.4 cm3 liquid scintillator volume and the reconstructed 3D dose map is compared along selected profiles and planes with radiochromic film and diode measurements. The comparison indicates that the 3DSD method agrees, within 25% for most points or within approximately 2 mm distance to agreement, with the relative radiochromic film and diode dose distributions in a small (approximately 4.5 mm high and approximately 12 mm diameter) volume in the unobstructed, high gradient dose region outside the edge of the plaque. For a comparison, the reproducibility of the radiochromic film results for our measurements ranges from 10 to 15% within this volume. At present, the 3DSD method is not accurate close to the edge of the plaque, and further than approximately 10 mm (<10% central axis depth dose) from the plaque surface. Improvement strategies, considered important to provide a more accurate quick check of the dose profiles in 3D for brachytherapy applicators, are discussed.