Transmission Potential of Asymptomatic and Paucisymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections: A 3-Family Cluster Study in China.

Data concerning the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic and paucisymptomatic patients are lacking. We report a 3-family cluster of infections involving asymptomatic and paucisymptomatic transmission. Eight of 15 (53%) members from 3 families were confirmed with SARS-CoV-2 infection. Of 8 patients, 3 were asymptomatic and 1 was paucisymptomatic. An asymptomatic mother transmitted the virus to her son, and a paucisymptomatic father transmitted the virus to his 3-month-old daughter. SARS-CoV-2 was detected in the environment of 1 household. The complete genomes of SARS-CoV-2 from the patients were > 99.9% identical and were clustered with other SARS-CoV-2 sequences reported from China and other countries.

Active smoking, sleep quality and cerebrospinal fluid biomarkers of neuroinflammation.

BACKGROUNDS: Cigarette smoking has been shown to be associated with sleep disorders and the related neuropathogenesis including neuroinflammation. Previous studies showed that pro- and anti-inflammatory cytokines are physiologically important in maintaining circadian function. In addition, sleep deprivation leads to immune dysregulations. However, no study has been published yet by using cerebrospinal fluid (CSF) biomarkers of neuroinflammation to investigate the relationship between active cigarette smoking and sleep disorders. METHODS: CSF tissues from subjects of 191 male subjects (non-smokers n = 104; active smokers n = 87) receiving local anesthesia before surgery for anterior cruciate ligament injuries were obtained after the assessment of clinical information and Pittsburgh Sleep Quality Index (PSQI). The levels of tumor necrosis factor alpha (TNFα), Interleukin (IL) 1 beta (IL1ß), IL2, IL4, IL6 and IL10 were measured using radioimmunoassay and ELISA. RESULTS: PSQI scores were significantly higher in active smokers than that in non-smokers (p < 0.001, Cohen's d = 0.63). Significantly higher levels of CSF TNFα were found in active smokers compared to non-smokers (28 ± 1.97 vs. 22.97 ± 2.48, p < 0.05, Cohen's d = 2.23). There was a positive correlation between CSF IL1ß levels and PSQI scores in non-smokers (r = 0.31, p = 0.01, adjustment R-Squared = 0.11). DISCUSSION: This is the first study to reveal the association between higher CSF TNFα levels and poorer sleep quality in active smoking. In addition, CSF IL1ß levels might be a potential biomarker in central nervous system for circadian dysregulation.

Correlations of Cerebrospinal Fluid/Plasma Fibroblast Growth Factor 21 Ratio with Metabolic Parameters in Chinese Individuals of Normal Weight.

BACKGROUND: Fibroblast growth factor 21 (FGF21) is an important metabolic regulator that has multiple beneficial effects on glucose homeostasis and lipid metabolism. Although circulating levels of FGF21 are mainly derived from liver, FGF21 is also found in other tissues and fluids including the cerebrospinal fluid (CSF). The aim of the present study was to investigate the relationships of CSF and/or plasma FGF21 levels with metabolic parameters in a normal-weight Chinese population. METHODS: Forty-five subjects (22 males and 23 females) were recruited from a patient population undergoing surgery for lower extremity injuries due to ligament damage or bone fractures below the knee in the Beijing Jishuitan Hospital. The levels of FGF21 in CSF and plasma were determined by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. RESULTS: No significant differences were detected in the levels of FGF21 in CSF and plasma between males (CSF: 158.01 ± 12.10 pg/mL; plasma: 206.19 ± 7.22 pg/mL) and females (CSF: 159.27 ± 17.85 pg/mL; plasma: 203.10 ± 7.53 pg/mL). The level of FGF21 in CSF was about 75% of that in plasma. The FGF21 level in CSF was positively correlated with triglyceride level, whereas plasma FGF21 level was negatively correlated with alanine aminotransferase in women but not in men. The CSF/plasma FGF21 ratio was positively correlated with CSF FGF21 in both genders and with peripheral glucose, triglyceride, and gamma-glutamyl transferase levels in female Chinese patients. CONCLUSIONS: These results have important implications regarding the potential central actions of FGF21.

Digital Anatomical Measurement for Anterolateral Fixation of Middle and Lower Thoracic Vertebrae.

BACKGROUND The key to its successful application is to determine the best entry point for the vertebral screw(s). This study aimed to provide a reference for clinical anterolateral fixation through digital measurement of computed tomography (CT) data to identify relevant anatomical positions in the middle and lower thoracic vertebrae (T4-T12) of 30 adults. MATERIAL AND METHODS We performed digital measurement of anatomical positions in the middle and lower thoracic vertebrae (T4-T12) of 30 adults. ABBREVIATIONS: Left height of vertebral body, LHV; Right height of vertebral body, RHV; Anterior height of vertebral body, AHV; Middle height of vertebral body, MHV; Posterior height of vertebral body, PHV; Superior sagittal diameter of vertebral body, SSDV; Superior transverse diameter of vertebral body, STDV; inferior sagittal diameter of vertebral body, ISDV; Inferior transverse diameter of vertebral body, ITDV; (1) Left (right) height of vertebral body, [L(R)HV]; Anterior (middle, posterior) height of vertebral body [A(M,P)HV]; Superior (inferior) sagittal diameter of vertebral body, [S(I)SDV]; Superior (inferior) transverse diameter of vertebral body, [S(I)TDV]. RESULTS The transverse diameters of vertebral bodies were always larger than the sagittal diameter for 3~4 mm. The distance between 2 vertebrae (interval of 1 vertebra) range were (52-56) mm for T4-T7 and (44-48) mm for T8-T12, and the surgeons could collate these data to choose a suitable stick length. CONCLUSIONS Bone graft should prune into laterigrade cuboid, it can recover A-P and bilateral physiological functions load, and the height of the vertebral body increased from T4 to T12.

Experimental Application of Bone Marrow Mesenchymal Stem Cells for the Repair of Intervertebral Disc Annulus Fibrosus.

BACKGROUND This study provides experimental results on the applicability of bone marrow mesenchymal stem cells (BMSCs) for the repair of intervertebral disc annulus fibrosus in rabbits. MATERIAL AND METHODS Thirty healthy rabbits were randomized into an observation group (n=15) and a control group (n=15). Both groups underwent degeneration of intervertebral disc annulus fibrosus. The observation group was treated with a solution of BMSCs and dexamethasone sodium phosphate, while the control group was treated with dexamethasone sodium phosphate only. RESULTS The two groups were compared for efficacy and pathological conditions after treatment. Both disc height index and level of type II collagen in nucleus pulposus were significantly higher in the observation group than in the control group at 2, 4, 8, and 12 weeks after degeneration (p<0.05 for all comparisons). The percentages of grade 0 and grade 1 were significantly higher in the observation group than in the control group (p<0.05 for both grade 0 and 1 comparisons), while the percentage of grade 4 and grade 5 were significantly lower in the observation group than in the control group (p<0.05 for both grade 4 and 5 comparisons). CONCLUSIONS BMSCs cultured in vitro can effectively repair intervertebral disc annulus fibrosus, which is of positive significance, and thus is clinically recommended.

Genetic polymorphisms of DNA repair pathways influence the response to chemotherapy and overall survival of gastric cancer.

We aimed to evaluate the clinical response to platinum-based chemotherapy and treatment outcome of gastric cancer patients in the present of ERCC1, ERCC2, NBN, RAD51, and XRCC3 gene polymorphisms. A number of 415 patients of gastric cancer that received platinum-based chemotherapy were enrolled in the present study. The presence of ERCC1 rs11615 and rs2298881, ERCC2 rs1799793 and rs13181, NBN rs1805794, rs709816, and RAD51 rs1801321 and XRCC3 rs1799794 were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Conditional regression analysis identified that CC genotype of ERCC1 rs11615 and AA genotype of ERCC2 rs1799793 was associated with a better response to chemotherapy in gastric cancer patients, and the odds ratio (ORs)(95% confidence interval (CI)) were 2.70(1.33-5.70) and 3.12(1.52-6.84), respectively. By the Cox analysis, the CC genotype of ERCC1 rs11615, AA genotype of ERCC2 rs1799793, and CC genotype of NBN rs1805794 were significantly associated with a longer overall survival (OS) of gastric cancer. In conclusion, our results suggest that ERCC1 rs11615, ERCC2 rs1799793, and NBN rs1805794 polymorphisms in the DNA repair pathways may influence the response to chemotherapy and OS of gastric cancer.

Cerebrospinal fluid oxytocin correlated with peripheral ALT and AST in Chinese female subjects.

OBJECTIVE: Oxytocin (OT) is primarily synthesized in the paraventricular nucleus of the hypothalamus and supraoptic nucleus of the hypothalamus in the central nervous system and exhibits a wide spectrum of central and peripheral activities. OT is involved in lipid metabolism and glucose homeostasis and plays a protective role against liver damage. METHODS: In this study, we investigated whether CSF OT levels correlates with peripheral glucose, lipid profiles, and/or liver enzymes in Chinese subjects. Sixty-nine subjects (n=36 males; n=33 females) who were recruited from Beijing Jishuitan Hospital participated in the study. Their levels of CSF OT and peripheral parameters were assayed by radioimmunoassay and continuous monitoring assay, respectively. RESULTS: There was no significant difference in CSF OT levels between males (53.09±6.88 nmol/mL) and females (52.34±6.87 nmol/mL), and no correlation found between CSF OT levels and peripheral glucose and lipid profiles. Significant negative correlation was observed between CSF OT levels and peripheral ALT and AST concentration in females but not in males. CONCLUSION: Our results support the physiological role of neuropeptides acting on brain sites to regulate liver enzymes, and shed new light on the brain-liver interaction.

Deep Learning-Based Reconstruction of 3D Morphology of Geomaterial Particles from Single-View 2D Images.

The morphology of particles formed in different environments contains critical information. Thus, the rapid and effective reconstruction of their three-dimensional (3D) morphology is crucial. This study reconstructs the 3D morphology from two-dimensional (2D) images of particles using artificial intelligence (AI). More than 100,000 particles were sampled from three sources: naturally formed particles (desert sand), manufactured particles (lunar soil simulant), and numerically generated digital particles. A deep learning approach based on a voxel representation of the morphology and multi-dimensional convolutional neural networks was proposed to rapidly upscale and reconstruct particle morphology. The trained model was tested using the three particle types and evaluated using different multi-scale morphological descriptors. The results demonstrated that the statistical properties of the morphological descriptors were consistent for the real 3D particles and those derived from the 2D images and the model. This finding confirms the model's validity and generalizability in upscaling and reconstructing diverse particle samples. This study provides a method for generating 3D numerical representations of geological particles, facilitating in-depth analysis of properties, such as mechanical behavior and transport characteristics, from 2D images.

Influence of coupled water and thermal treatments on the fracture characteristics of a typical sandstone.

Understanding the fracture behavior of rock after coupled water and thermal environment is important for many geotechnical projects. This study examines the influence of coupled water and thermal treatments on the fracture toughness and characteristics of a typical sandstone under mode I and mode II loading conditions. Notched deep beam (NDB) specimens were utilized and subjected to soaking treatments at various water temperatures (23 °C, 60 °C, and 99 °C). The experimental results indicate a significant reduction in both mode I and mode II fracture toughness values, with reductions ranging from 15.4% to 13.2% for mode I and 26.1% to 8.9% for mode II respectively. As the water temperatures increase, a slightly rising trend is observed in both mode I and mode II fracture toughness within the examined temperature range. Sandstone specimens displayed typical brittle fracture characteristics at lower soaking temperatures. For mode I specimens, an increase in ductility was evident with higher soaking temperatures, while the ductile behavior is less pronounced in the mode II specimens. Based on the Maximum Tangential Stress (MTS) criterion and the Generalized Maximum Tangential Stress (GMTS) criterion, the predicted values of mode II fracture toughness and the fracture process zone (FPZ) were discussed. The results show that both the GMTS and MTS criteria exhibit inaccuracies in predicting the mode II fracture toughness of sandstone treated at different soaking water temperatures. However, the GMTS criterion, which incorporates T-stress, demonstrates smaller errors compared to the MTS criterion. The study shows that the radius r0 of the fracture process zone is not a constant under both mode I and mode II loading conditions. The calculation of the fracture process zone radius r0 in the GMTS criterion requires further theoretical and experimental study.

The effect of the interaction of sleep onset latency and age on ischemic stroke severity via inflammatory chemokines.

Objective: Prolonged sleep onset latency (PSOL) and age have been linked to ischemic stroke (IS) severity and the production of chemokines and inflammation, both of which contribute to IS development. This study aimed to explore the relationship between chemokines, inflammation, and the interplay between sleep onset latency (SOL) and age in influencing stroke severity. Methods: A cohort of 281 participants with mild to moderate IS was enrolled. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS), and SOL was recorded. Serum levels of macrophage inflammatory protein-1alpha (MIP-1α), macrophage inflammatory protein-1beta (MIP-1ß), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured. Results: NIHSS scores of middle-aged participants with PSOL were significantly higher than those with normal sleep onset latency (NSOL) (p = 0.046). This difference was also observed when compared to both the elderly with NSOL (p = 0.022), and PSOL (p < 0.001). Among middle-aged adults with PSOL, MIP-1ß exhibited a protective effect on NIHSS scores (ß = -0.01, t = -2.11, p = 0.039, R2 = 0.13). MIP-1α demonstrated a protective effect on NIHSS scores in the elderly with NSOL (ß = -0.03, t = -2.27, p = 0.027, R2 = 0.12). Conclusion: This study reveals a hitherto undocumented association between PSOL and IS severity, along with the potential protective effects of MIP-1ß in mitigating stroke severity, especially among middle-aged patients.

[Effects on serum estadiol and progesterone of female mice exposed to arsenic chronically].

OBJECTIVE: By measure the changes of serumal estadiol and progesterone levels of kunming female mice, which are chronically exposed to different concentrations of arsenic trioxide, discuss the estrogen-like effects of arsenic. METHODS: Select the Kunming female mice exposed to different drinking water of arsenic trioxide (0, 0.05, 0.10, 0.20, 0.40 microg/ml) for 20 weeks as the research subjects in this study. Use the method of radioimmunology to measure concentrations of serumal estadiol and progesterone of female adult mice. RESULTS: Compared with the control group, there exists the changes of the concentrations of the serumal estadiol and progesterone of Km female adult mice, which are chronically exposed to the arsenic. Compared to the control group, the differences of the concentrations of the serumal estadiol in the 0.05 microg/ml group and 0.10 microg/ml group have no statistical significance (P > 0.05), the concentrations of estadiol in the 0.20 microg/ml group (P < 0.01) and 0.40 microg/ ml group (P < 0.05) decrease. Compared to the control group, the differences of the concentrations of the serumal progesterone in the 0.05 microg/ml group, 0.20 microg/ml group and 0.40 microg/ml group have no statistical significance (P > 0.05), the concentration of serumal progesterone in the 0.10 microg/ml group (P < 0.01) decrease. CONCLUSION: Chronically arsenic exposure can interfere the levels of serumal hormones. Arsenic has the estrogen-like effects.

The Association Between Hypoxia Improvement and Electroconvulsive Therapy for Major Depressive Disorder.

BACKGROUND: The occurrence of depression was related with a state of mild hypoxia for a long time. Hypoxia-inducible factor-2α (HIF-2α) modulates the process from acute to chronic hypoxia, consequently regulating changes in inducible nitric oxide synthase (iNOS). Increasing levels of iNOS combined with major depressive disorder (MDD) have been associated with the concentration of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which increase the severity of depression. OBJECTIVE: The aim was to investigate whether depressive symptoms might be improved by regulating HIF-2α levels to decrease the degree of oxidative stress and inflammation using electroconvulsive therapy (ECT). METHODS: In this observational study, 49 MDD patients were divided into the ECT group (n=32) and control group (n=17). The Hamilton Depression Rating Scale (HAMD) was used to evaluate depressive symptoms of patients at enrollment and after 2 weeks of treatment. The levels of HIF-2α, NOS, IL-6, and TNF-α in plasma were analyzed accordingly. RESULTS: The total score in each dimension of HAMD decreased more efficiently in the ECT group than in the control group (p < 0.05). The plasma levels of IL-6 in the ECT group were notably decreased after the 2-week treatment (t = 3.596, p = 0.001). The decreased trend to statistical significance of HIF-2α was observed after treatment in the ECT group (p = 0.091). CONCLUSION: The present study demonstrated that the therapeutic effects of long-term ECT therapy for MDD may further benefit from and contribute to the improvement of MDD-associated chronic hypoxia.

Association of Cigarette Smoking With Male Cognitive Impairment and Metal Ions in Cerebrospinal Fluid.

Objective: Cigarette smoking might accelerate cognitive impairment; however, this has never been investigated using human cerebrospinal fluid (CSF). We conducted this study to investigate the association between cigarette smoking and cognitive impairment through metal ions in CSF. Methods: We obtained 5-ml CSF samples from routine lumbar puncture procedures in patients undergoing anterior cruciate ligament reconstruction before surgery in China. A total of 180 Chinese males were recruited (80 active smokers and 100 non-smokers). We measured specific cigarette-related neurotoxic metal ions in CSF, including iron, copper, zinc, lead, aluminum, and manganese. Sociodemographic data and history of smoking were obtained. The Montreal Cognitive Assessment (MoCA) was applied. Results: Active smokers had fewer years of education (11.83 ± 3.13 vs. 13.17 ± 2.60, p = 0.01), and higher age (33.70 ± 10.20 vs. 29.76 ± 9.58, p = 0.01) and body mass index (25.84 ± 3.52 vs. 24.98 ± 4.06, p =0.03) than non-smokers. Compared to non-smokers, active smokers had significantly higher CSF levels of iron, zinc, lead, and aluminum and lower MoCA scores (all p < 0.05). Average daily numbers of cigarettes smoked negatively correlated with the MoCA scores (r = -0.244, p = 0.048). In young smokers, CSF manganese levels negatively correlated with MoCA scores (r = -0.373, p = 0.009). Conclusions and Relevance: Cigarette smoking might be associated with male cognitive impairment, as shown by lower MoCA scores and higher levels of CSF iron, zinc, lead, and aluminum in active smokers. This might be early evidence of cigarette smoking accelerating male cognitive impairment.

Transcriptome Analysis of Peripheral Blood Mononuclear Cells in SARS-CoV-2 Naïve and Recovered Individuals Vaccinated With Inactivated Vaccine.

The urgent approval of the use of the inactivated COVID-19 vaccine is essential to reduce the threat and burden of the epidemic on global public health, however, our current understanding of the host immune response to inactivated vaccine remains limited. Herein, we performed serum IgG antibody detection and transcriptomics analysis on 20 SARS-CoV-2 naïve individuals who received multiple doses of inactivated vaccine and 5 SARS-CoV-2 recovered individuals who received single dose of inactivated vaccine. Our research revealed the important role of many innate immune pathways after vaccination, identified a significant correlation with the third dose of booster vaccine and proteasome-related genes, and found that SARS-CoV-2 recovered individuals can produces a strong immune response to a single dose of inactivated vaccine. These results help us understand the reaction mechanism of the host's molecular immune system to the inactivated vaccine, and provide a basis for the choice of vaccination strategy.

Lasting antibody and T cell responses to SARS-CoV-2 in COVID-19 patients three months after infection.

The dynamics, duration, and nature of immunity produced during SARS-CoV-2 infection are still unclear. Here, we longitudinally measured virus-neutralising antibody, specific antibodies against the spike (S) protein, receptor-binding domain (RBD), and the nucleoprotein (N) of SARS-CoV-2, as well as T cell responses, in 25 SARS-CoV-2-infected patients up to 121 days post-symptom onset (PSO). All patients seroconvert for IgG against N, S, or RBD, as well as IgM against RBD, and produce neutralising antibodies (NAb) by 14 days PSO, with the peak levels attained by 15-30 days PSO. Anti-SARS-CoV-2 IgG and NAb remain detectable and relatively stable 3-4 months PSO, whereas IgM antibody rapidly decay. Approximately 65% of patients have detectable SARS-CoV-2-specific CD4+ or CD8+ T cell responses 3-4 months PSO. Our results thus provide critical evidence that IgG, NAb, and T cell responses persist in the majority of patients for at least 3-4 months after infection.

Association of Cigarette Smoking With Cerebrospinal Fluid Biomarkers of Neurodegeneration, Neuroinflammation, and Oxidation.

Importance: Cigarette smoking has been associated with risk of neurodegenerative disorders, such as Alzheimer disease. The association between smoking and biomarkers of changes in human cerebrospinal fluid (CSF) is not fully understood. Objective: To investigate the association of cigarette smoking with CSF biomarkers of neurodegeneration, neuroinflammation, oxidation, and neuroprotection. Design, Setting, and Participants: In this case-control study of 191 adult men in China, biomarkers in the CSF of participants with and without significant cigarette exposure were examined. Participants who did not smoke and had no history of substance use disorder or dependence were assigned to the nonsmoking group. The active smoking group included participants who consumed at least 10 cigarettes per day for 1 year. Five-milliliter samples of CSF were obtained from routine lumbar puncture conducted before anterior cruciate ligament reconstruction surgery. Data collection took place from September 2014 to January 2016, and analysis took place from January to February 2016. Exposures: Cigarette smoking. Main Outcomes and Measures: CSF levels of ß-amyloid 42 (Aß42), which has diagnostic specificity for Alzheimer disease, tumor necrosis factor alpha (TNFα), brain-derived neurotrophic factor (BDNF), total superoxide dismutase (SOD), and nitric oxide synthase (NOS) were measured. Sociodemographic data and history of smoking were obtained. Results: Of 191 participants, 87 (45.5%) were included in the active smoking group and 104 (54.4%) in the nonsmoking group. Compared with the active smoking group, the nonsmoking group was younger (mean [SD] age, 34.4 [10.5] years vs 29.6 [9.5] years; P = .01), had more education (mean [SD] duration of education, 11.9 [3.1] years vs 13.2 [2.6] years; P = .001), and had lower body mass index (mean [SD], 25.9 [3.6] vs 24.9 [4.0]; P = .005). Comparing the nonsmoking group with the smoking group, mean (SD) CSF levels of Aß42 (38.0 [25.9] pg/mL vs 52.8 [16.5] pg/mL; P < .001) and TNFα (23.0 [2.5] pg/mL vs 28.0 [2.0] pg/mL; P < .001) were significantly lower, while BDNF (23.1 [3.9] pg/mL vs 13.8 [2.7] pg/mL; P < .001), total SOD (15.7 [2.6] U/L vs 13.9 [2.4] U/L; P < .001), total NOS (28.3 [7.2] U/L vs 14.7 [5.6] U/L; P < .001), inducible NOS (16.0 [5.4] U/L vs 10.3 [2.7] U/L; P < .001), and constitutive NOS (12.4 [6.9] U/mL vs 4.4 [3.9] U/mL) were higher. In addition, in participants in the smoking group who were aged 40 years or older, total SOD levels were negatively correlated with Aß42 levels (r = -0.57; P = .02). In those who smoked at least 20 cigarettes per day, TNFα levels were positively correlated with Aß42 levels (r = 0.51; P = .006). The association of TNFα with Aß42 production was stronger than that of total SOD with Aß42 production (z = -4.38; P < .001). Conclusions and Relevance: This case-control study found that cigarette smoking was associated with at-risk biomarkers for Alzheimer disease, as indicated by higher Aß42 levels, excessive oxidative stress, neuroinflammation, and impaired neuroprotection found in the CSF of participants in the active smoking group.

Association between IL-10 gene polymorphisms and the risk of ischemic stroke in a Chinese population.

We investigated the possible association between two SNPs of IL-10 (IL-10 -1082A/G and -819T/C) and the susceptibility to ischemic stroke. Patients with proven ischemic stroke and control subjects were recruited between March 2013 and May 2015. The IL-10 -1082A/G and -819T/C polymorphisms were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Conditional logistic regression analyses revealed that the GA and the AA genotypes were associated with development of ischemic stroke, and the ORs (95% CI) for the GA and the AA genotypes of IL-10 -1082A/G were 1.49 (1.01-2.19) and 1.83 (1.02-3.29) compared with the GG genotype, respectively. In dominant model, the GA+AA genotype of IL-10 -1082G/A was correlated with increased risk of ischemic stroke compared to the GG genotype (OR=1.56, 95% CI=1.08-2.25). The GA+AA genotype was associated with moderately increased risk of ischemic stroke in smokers (OR=1.72, 95% CI=1.04-2.84). In conclusion, our study suggests that IL-10 gene polymorphisms contribute to the development of ischemic stroke, especially in tobacco smokers.

Farnesoid X receptor antagonizes JNK signaling pathway in liver carcinogenesis by activating SOD3.

The farnesoid X receptor (FXR) is a key metabolic and homeostatic regulator in the liver. In the present work, we identify a novel role of FXR in antagonizing c-Jun N-terminal kinase (JNK) signaling pathway in liver carcinogenesis by activating superoxide dismutase 3 (SOD3) transcription. Compared with wild-type mouse liver, FXR(-/-) mouse liver showed elevated JNK phosphorylation. JNK1 deletion suppressed the increase of diethylnitrosamine-induced tumor number in FXR(-/-) mice. These results suggest that JNK1 plays a key role in chemical-induced liver carcinogenesis in FXR(-/-) mice. We found that ligand-activated FXR was able to alleviate H2O2or tetradecanoylphorbol acetate-induced JNK phosphorylation in human hepatoblastoma (HepG2) cells or mouse primary hepatocytes. FXR ligand decreased H2O2-induced reactive oxygen species (ROS) levels in wild-type but not FXR(-/-) mouse hepatocytes. FXR knockdown abolished the inhibition of 3-[2-[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]-Benzoic acid (GW4064) on JNK phosphorylation and ROS production induced by H2O2in HepG2 cells. The gene expression of SOD3, an antioxidant defense enzyme, was increased by FXR activation in vitro and in vivo. An FXR-responsive element, inverted repeat separated by 1 nucleotide in SOD3 promoter, was identified by a combination of transcriptional reporter assays, EMSAs, and chromatin immunoprecipitation assays, which indicated that SOD3 could be a direct FXR target gene. SOD3 knockdown abolished the inhibition of GW4064 on JNK phosphorylation induced by H2O2in HepG2 cells. In summary, FXR may regulate SOD3 expression to suppress ROS production, resulting in decreasing JNK activity. These results suggest that FXR, as a novel JNK suppressor, may be an attractive therapeutic target for liver cancer treatment.

Diet folate, DNA methylation and polymorphisms in methylenetetrahydrofolate reductase in association with the susceptibility to gastric cancer.

Methylenetetrahydrofolate reductase (MTHFR) has been reported to be associated with DNA methylation, an epigenetic feature frequently found in gastric cancer. We conducted a case-control study to explore the association of MTHFR C677T polymorphisms with gastric cancer risk and its relation with the DNA methylation of COX-2, MGMT, and hMLH1 genes. Genotyping of P16, MGMT and HMLH1 was determined by methylation-specific PCR after sodium bisulfate modification of DNA, and genotyping of MTHFR C677T was conducted by TaqMan assays using the ABI Prism 7911HT Sequence Detection System. Folate intake was calculated with the aid of a questionnaire. Compared with the MTHFR 677CC genotype, the TT genotype was significantly associated with 2.08 fold risk of gastric cancer when adjusting for potential risk factors. Individuals who had an intake of folate above 310 µg/day showed protective effects against gastric cancer risk. The effect of MTHFR C677T polymorphisms on the risk of gastric cancer was modified by folate intake and methylation status of MGMT (P for interaction <0.05).

Lower serum interleukin-2 levels in schizophrenic patients with tardive dyskinesia.

We determined serum interleukin-2 (IL-2) levels between schizophrenic patients with (n=45) and without tardive dyskinesia (TD; n=45) compared to normal controls (n=50). TD patients had lower serum IL-2 levels than non-TD patients, but higher IL-2 levels than normal controls. IL-2 was associated with the negative symptoms of schizophrenia, but not with TD severity. Immune disturbance may be involved in the pathophysiology of TD.