ABSTRACT
BACKGROUND: Although CDKN2A alteration has been explored as a favorable factor for tumorigenesis in pan-cancers, the association between CDKN2A point mutation (MUT) and intragenic deletion (DEL) and response to immune checkpoint inhibitors (ICIs) is still disputed. This study aims to determine the associations of CDKN2A MUT and DEL with overall survival (OS) and response to immune checkpoint inhibitors treatment (ICIs) among pan-cancers and the clinical features of CDKN2A-altered gastric cancer. METHODS: This study included 45,000 tumor patients that underwent tumor sequencing across 33 cancer types from four cohorts, the MSK-MetTropism, MSK-IMPACT, OrigiMed2020 and TCGA cohorts. Clinical outcomes and genomic factors associated with response to ICIs, including tumor mutational burden, copy number alteration, neoantigen load, microsatellite instability, tumor immune microenvironment and immune-related gene signatures, were collected in pan-cancer. Clinicopathologic features and outcomes were assessed in gastric cancer. Patients were grouped based on the presence of CDKN2A wild type (WT), CDKN2A MUT, CDKN2A DEL and CDKN2A other alteration (ALT). RESULTS: Our research showed that CDKN2A-MUT patients had shorter survival times than CDKN2A-WT patients in the MSK MetTropism and TCGA cohorts, but longer OS in the MSK-IMPACT cohort with ICIs treatment, particularly in patients having metastatic disease. Similar results were observed among pan-cancer patients with CDKN2A DEL and other ALT. Notably, CDKN2A ALT frequency was positively related to tumor-specific objective response rates to ICIs in MSK MetTropism and OrigiMed 2020. Additionally, individuals with esophageal carcinoma or stomach adenocarcinoma who had CDKN2A MUT had poorer OS than patients from the MSK-IMPACT group, but not those with adenocarcinoma. We also found reduced levels of activated NK cells, T cells CD8 and M2 macrophages in tumor tissue from CDKN2A-MUT or DEL pan-cancer patients compared to CDKN2A-WT patients in TCGA cohort. Gastric cancer scRNA-seq data also showed that CDKN2A-ALT cancer contained less CD8 T cells but more exhausted T cells than CDKN2A-WT cancer. A crucial finding of the pathway analysis was the inhibition of three immune-related pathways in the CDKN2A ALT gastric cancer patients, including the interferon alpha response, inflammatory response, and interferon gamma response. CONCLUSIONS: This study illustrates the CDKN2A MUT and DEL were associated with a poor outcome across cancers. CDKN2A ALT, on the other hand, have the potential to be used as a biomarker for choosing patients for ICI treatment, notably in esophageal carcinoma and stomach adenocarcinoma.
Subject(s)
Cyclin-Dependent Kinase Inhibitor p16 , Stomach Neoplasms , Tumor Microenvironment , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/immunology , Cyclin-Dependent Kinase Inhibitor p16/genetics , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Male , Female , Immune Checkpoint Inhibitors/therapeutic use , Middle Aged , Biomarkers, Tumor/genetics , Aged , Prognosis , DNA Copy Number Variations/genetics , Mutation/genetics , Microsatellite InstabilityABSTRACT
OBJECTIVE: To evaluate the value of high-resolution ultrasound the diagnosis and prognosis of cubital tunnel syndrome. METHODS: From January 2018 to June 2019, 47 patients with cubital tunnel syndrome were treated with ulnar nerve release and anterior subcutaneous transposition. There were 41 males and 6 females, aged from 27 to 73 years old. There were 31 cases on the right, 15 cases on the left, and 1 case on both sides. The diameter of ulnar nerve was measured by high-resolution ultrasound pre-and post-operatively, and measured directly during the operation. The recovery status of the patients was evaluated by the trial standard of ulnar nerve function assessment, and the satisfaction of the patients was assessed. RESULTS: All the 47 cases were followed up for an average of 12 months and the incisions healed well. The diameter of ulnar nerve at the compression level was (0.16±0.04) cm pre-operatively, and the diameter of ulnar nerve was (0.23±0.04) cm post-operatively. The evaluation of ulnar nerve function:excellent in 16 cases, good in 18 cases and fair in 13 cases. Twelve months post-operatively, 28 patients were satisfied, 10 patients were general and 9 patients were dissatisfied. CONCLUSION: The preoperative examination of ulnar nerve by high-resolution ultrasound is consistent with the intuitive measurement during operation, and the result of postoperative examination of ulnar nerve by high-resolution ultrasound is consistent with follow-up results. High-resolution ultrasound is an effective auxiliary method for the diagnosis and treatment of cubital tunnel syndrome.
Subject(s)
Cubital Tunnel Syndrome , Male , Female , Humans , Adult , Middle Aged , Aged , Cubital Tunnel Syndrome/diagnostic imaging , Cubital Tunnel Syndrome/surgery , Ulnar Nerve/diagnostic imaging , Ulnar Nerve/surgery , Neurosurgical Procedures/methods , Decompression, Surgical/methods , PrognosisABSTRACT
PURPOSE: To study thickness of RPE-BM complex in adult Chinese subjects and its correlation with systemic and ocular biometric parameters. DESIGN: Population-based longitudinal study. Cross-sectional study. PARTICIPANTS: The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6 ± 9.8 years (range: 50-93 years). METHODS: A detailed ophthalmic examination was performed including spectral-domain optical coherence tomography (SD OCT) for measurement of the thickness of RPE-BM complex. Use Heidelberg software "Heidelberg Eye Explorer" for segmentation and measurements. MAIN OUTCOME MEASURE: Thickness of RPE-BM complex. RESULTS: In total, 3276 people (6530 eyes) were included in the study. In total, 1844 (56.3%) subjects were female. The mean age was 64.3 ± 9.6 years (range: 50-93 years). The mean refractive error (spherical equivalent) was -0.18 ± 2.04 diopters (range: -22.0 to +7.50 diopters). Mean thickness of the RPE-BM complex at the foveal center was 25.09 ± 3.98 µm (range: 17-37 µm). In multiple regression analysis, subfoveal thickness of the RPE-BM complex was associated with age (p = 0.039; beta: 0.22; B: 0.10 (95% CI: 0.01, 0.20)) and hypertension history (p = 0.038; beta: 0.23; B: 1.96 (95% CI: 0.12, 3.81)). CONCLUSION: Mean subfoveal thickness of the RPE-BM complex was 25.09 ± 3.98 µm in elderly subjects with a mean age of 64.3 years increased with age and hypertension history. The increase in the thickness of RPE-BM complex may play a role in the pathophysiologic features of various age-related ocular conditions.
Subject(s)
Bruch Membrane , Retinal Pigment Epithelium , Humans , Adult , Female , Aged , Middle Aged , Male , Retinal Pigment Epithelium/diagnostic imaging , Tomography, Optical Coherence/methods , Cross-Sectional Studies , East Asian People , Longitudinal StudiesABSTRACT
This meta-analysis aimed to analyze retinal microvasculature features in eyes with Behçet's disease (BD) using optical coherence tomography angiography (OCTA). Electronic databases, including PubMed, Web of Science, Embase, and Cochrane Library, were comprehensively searched for published studies comparing retinal microvasculature characteristics between eyes with BD and controls. Continuous variables were calculated using the mean difference (MD) with 95% confidence interval (CI). Review Manager software (version 5.30) was used to conduct statistical analysis. A total of 13 eligible studies involving 599 eyes with BD and 622 control eyes were included in the meta-analysis. The pooled results showed that the macular whole enface superficial and deep vessel density (VD) values measured by OCTA were significantly lower in eyes with BD than in control eyes (superficial VD: MD = - 3.05, P < 0.00001; deep VD: MD = - 4.05, P = 0.0004). The foveal superficial and deep VD values were also significantly lower in the BD group than in the control group (superficial VD: MD = - 1.50, P = 0.009; deep VD: MD = - 4.25, - = 0.03). Similarly, the analysis revealed a significant reduction in the parafoveal superficial and deep VD in eyes with BD than in control eyes (superficial VD: MD = - 3.68, P < 0.00001; deep VD: MD = - 4.95, P = 0.0007). In addition, the superficial and deep foveal avascular zones (FAZs) were significantly larger in patients with BD than in controls (superficial FAZ: MD = 0.06, P = 0.02; deep FAZ: MD = 0.12, P = 0.03). The present meta-analysis found that macular whole enface VD, foveal VD, and parafoveal VD were lower in eyes with BD, and the FAZ was larger in patients with BD. The findings suggest that OCTA can assist clinicians in diagnosing and monitoring the status of patients with BD.
Subject(s)
Behcet Syndrome/pathology , Microvessels/pathology , Retinal Vessels/pathology , Adult , Behcet Syndrome/complications , Behcet Syndrome/diagnostic imaging , Female , Fovea Centralis/blood supply , Humans , Macula Lutea/blood supply , Macular Edema/diagnostic imaging , Macular Edema/etiology , Male , Microvessels/diagnostic imaging , Middle Aged , Retinal Vasculitis/diagnostic imaging , Retinal Vasculitis/etiology , Retinal Vessels/diagnostic imaging , Tomography, Optical CoherenceABSTRACT
Purpose: This study aimed to quantitative assess the fundus tessellated density (FTD) and associated factors on the basis of fundus photographs using artificial intelligence. Methods: A detailed examination of 3468 individuals was performed. The proposed method for FTD measurements consists of image preprocessing, sample labeling, deep learning segmentation model, and FTD calculation. Fundus tessellation was extracted as region of interest and then the FTD could be obtained by calculating the average exposed choroid area of per unit area of fundus. Besides, univariate and multivariate linear regression analysis have been conducted for the statistical analysis. Results: The mean FTD was 0.14 ± 0.08 (median, 0.13; range, 0-0.39). In multivariate analysis, FTD was significantly (P < 0.001) associated with thinner subfoveal choroidal thickness, longer axial length, larger parapapillary atrophy, older age, male sex and lower body mass index. Correlation analysis suggested that the FTD increased by 33.1% (r = 0.33, P < .001) for each decade of life. Besides, correlation analysis indicated the negative correlation between FTD and spherical equivalent (SE) in the myopia participants (r = -0.25, P < 0.001), and no correlations between FTD and SE in the hypermetropia and emmetropic participants. Conclusions: It is feasible and efficient to extract FTD information from fundus images by artificial intelligence-based imaging processing. FTD can be widely used in population screening as a new quantitative biomarker for the thickness of the subfoveal choroid. The association between FTD with pathological myopia and lower visual acuity warrants further investigation. Translational Relevance: Artificial intelligence can extract valuable clinical biomarkers from fundus images and assist in population screening.
Subject(s)
Artificial Intelligence , Myopia, Degenerative , Aged , Cross-Sectional Studies , Fundus Oculi , Humans , Male , Tomography, Optical CoherenceABSTRACT
Although negative life events are a risk factor for developing depression, cognitive control can help maintain one's mental health. However, whether thought-control ability (TCA) can alleviate the adverse effects of negative life events on depression is unclear. Therefore, two studies were conducted to test if it does, by having participant's complete measures of negative life events, TCA, and depression. Study 1, which included 140 healthy young adults, showed TCA mediated the relationship between negative life events and depressive symptoms, and that TCA also moderated the relationship between negative life events and depressive symptoms. Study 2 recruited patients with major depressive disorder (MDD) to test whether the findings could be generalized to individuals with MDD. Study 2 found TCA also mediated the relationship between negative life events and symptoms of MDD. Suggesting that improving the ability to control negative thoughts in daily life help maintain mental health and prevent depressive symptoms.
ABSTRACT
BACKGROUND: Abnormal lipid metabolism is closely associated with the invasiveness and metastasis of cancer. Fatty acid-binding proteins (FABPs) play essential roles in lipid metabolism, and miRNAs can affect lipid metabolism by targeting FABPs. However, the exact mechanism is unknown. METHODS: FABP1 expression in HCC tissues was analyzed by immunochemistry with tissue microarrays. The lipid content was detected by Oil Red O staining, and the interaction between FABP1 and free fatty acid (FFA) was studied by a labeling and tracking method. miRNA arrays were used to detect the expression of miRNAs in IL-6-stimulated HCC cells. miR-603 expression was verified by qPCR. The proteins were checked by Western blot analysis. Gain and loss function evaluation was assessed by lentivirus and miRNA mimic transfection in Huh-7 cells, while reactive oxygen species (ROS) were detected by fluorescence. RESULTS: FABP1 expression was significantly decreased in approximately 90% (81/90) of HCC patients. FABP1 expression in adjacent tissues was closely associated with overall survival. Meanwhile, lipid was abundant in the adjacent tissues, yet significantly reduced in HCC tissues. FABP1 and FFA can promote each other for being uptaken by Huh-7 cells. FABP1 overexpression induced apoptosis and inhibited the proliferation, migration, invasion, and metastasis of Huh-7 cells. IL-6 treatment affected the expression of miRNAs, and miR-603 was overexpressed in HCC tissues. Also, miR-603 overexpression promoted the proliferation, migration, invasion, and metastasis of Huh-7 cells. Bioinformatic analysis predicted that miR-603 targets the 3'-UTR region of FABP1. However, miR-603 overexpression inhibited the expression of the FABP1 but increased the CPT1A, PPAR-α, and SREBP1 expressions. FABP1 overexpression reduced ROS in HCC cells, while miR-603 can reverse these effects. CONCLUSION: Our results indicate that in the pathogenesis of HCC, IL-6 induces miR-603 expression, which subsequently inhibits FABP1 expression, promotes the lipid metabolism- and synthesis-related proteins, and finally increases the cellular oxidative stress level and leads to the metastasis of HCC.
Subject(s)
Carcinoma, Hepatocellular/metabolism , Fatty Acid-Binding Proteins/metabolism , Interleukin-6/metabolism , Liver Neoplasms/metabolism , MicroRNAs/metabolism , Signal Transduction , 3' Untranslated Regions , Apoptosis , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation , Fatty Acid-Binding Proteins/genetics , Fatty Acids/metabolism , Gene Expression Regulation, Neoplastic , Hep G2 Cells , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathologyABSTRACT
Purpose: To predict the prognosis of craniopharyngioma in children by optical coherence tomography angiography (OCTA). Methods: We evaluated if the relationship between preoperative OCTA of the choroidal capillary density (CCD) and visual outcome continued over long-term visual recovery in 38 patients undergoing craniopharyngioma resection. Patients were evaluated 3 times: 1 week before surgery (Visit1), followed-up at 6-10 weeks (Visit2), and 9-15 months (Visit3) after surgery. Results: In total 38 patients (70 eyes) with craniopharyngiomas, which included 20 (52.6%) boys and 18 (47.4%)girls, the mean age was 11.8 ± 2.7 years (range: 6-18 years). The age (p = 0.71), gender (p = 1.00), mean refractive error (p = 0.55), and axial length (p = 0.23) of 38 normal volunteers (76 eyes) were matched. After surgery, the cross-compression of patients was relieved. The average visual acuity change in the normal CCD group was 0.07 ± 0.02; the average visual acuity change in the low CCD group was 0.01 ± 0.01, p < 0.001. Preoperative CCD value is related to the preoperative BCVA (p < 0.001), and the visual function after the long-term follow-up (9-15 months) (p < 0.001). The prognosis of CCD has the same trend as the BCVA. Further correlation analysis shows that CCD and BCVA are significantly correlated (r = 0.878; p < 0.001). CCD has a weak but significant correlation both with MD (r = 0.19; p < 0.001) and PSD (r = -0.21; p <0.001). A natural cutoff of CCD is approximately 38%. With the normal CCD group the maximum improvement of BCVA exceeds 0.3 post-operatively, compared to eyes in the low CCD group that improve by <0.03, and worse after surgery. Conclusions: Long-term vision recovery after surgical decompression of craniopharyngiomas in children can be predicted by preoperative by OCTA. Patients with normal CCD before surgery showed a tendency to improve vision; this trend of improvement persisted in subsequent follow-ups. The CCD baseline natural cutoff value for predicting visual prognosis before and after surgery is about 38%.
ABSTRACT
The present study aimed to elucidate the effects of dexmedetomidine on kidney injury of parturients with preeclampsia (PE) undergoing cesarean section. Total 134 cesarean delivery women with PE were randomly divided into intervention group (IG) and control group (CG). Both groups underwent combined spinal and epidural anesthesia (CSEA), the IG was treated with 0.4 µg/(kg·min) dexmedetomidine for 10 min before surgery. The CG was treated with equivalent saline. Heart rate (HR), blood pressure, oxygen saturation (SpO2) of the two groups were measured at different time point after administration. Level of inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). Visual analogue score (VAS), Ramsay sedation score (RSS), and kidney injury related indexes were evaluated at different time points. The plasma-drug concentration of patients was determined by High Performance Liquid Chromatography (HPLC) method. Compared with CG, HR, PE, and diastolic blood pressure (DBP) showed lower level while SpO2 showed higher level in IG. Furthermore, expression of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and IL-10 in IG was decreased after drug administration, the contents of ß2-MG, KIM-1 and urine protein were also decreased in contrast to the CG (all P<0.05). Besides, VAS score was decreased but Ramsay score was increased in the IG (both P<0.05). The results of HPLC showed that the half life of dexmedetomidine was about 20 min and it is speculated that the drug can be quickly metabolized within 24 h. Dexmedetomidine exerted protective effects on kidney injury of parturients with PE undergoing cesarean section.
Subject(s)
Acute Kidney Injury/prevention & control , Cesarean Section , Dexmedetomidine/administration & dosage , Pre-Eclampsia/drug therapy , Acute Kidney Injury/blood , Acute Kidney Injury/etiology , Acute Kidney Injury/physiopathology , Adult , Dexmedetomidine/adverse effects , Double-Blind Method , Female , Humans , Male , Pre-Eclampsia/blood , Pre-Eclampsia/physiopathology , PregnancyABSTRACT
To study types and thickness of interdigitation zone band in adult Chinese subjects, we conducted a cross-sectional study. The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6 ± 9.8 years. 263 people (263eyes) with a mean age of 64.8 years were randomly selected cases without macular diseases included in the study. A detailed ophthalmic examination was performed including SD-OCT for measurement of the thickness of interdigitation zone band. There are two types of interdigitation zone band; the type1 which can distinguish RPE-BM complex in 170 eyes; and the Type 2 which the two layers merged involved 93 eyes. In type1, the mean thickness of the interdigitation zone band was significantly thicker in the foveal center (16.46 ± 2.92 µm), then nasal macular region (16.19 ± 2.69 µm), temporal macular region (15.73 ± 2.68 . µm), superior region (15.72 ± 2.70 µm), and inferior macular region (14.84 ± 2.63 µm) (P all < 0.05). And the mean thickness of the interdigitation zone band in the foveal center associated with the subfoveal choroidal thickness (P = 0.025) and level of education (P = 0.033). The increase in the thickness of the interdigitation zone band may play a role in the pathophysiologic features of various age-related ocular conditions.
Subject(s)
Fovea Centralis/pathology , Macula Lutea/pathology , Macular Degeneration/diagnosis , Retinal Pigment Epithelium/pathology , Tomography, Optical Coherence/methods , Adult , Aged , China , Cross-Sectional Studies , Diagnostic Techniques, Ophthalmological , Humans , Macular Degeneration/pathology , Male , Middle Aged , Population Groups , Visual AcuityABSTRACT
To investigate the relationship between acetyl cholinesterase associated collagen gene (COLQ) mutation in patients with acetyl cholinesterase deficiency and its clinical characteristics. Serum and red blood cell acetyl cholinesterase from patients with acetyl cholinesterase deficiency (n=6) and normal controls (n=20) were measured by butyryl thiocholine substrate. COLQ gene variations were detected by sequencing. And the cholinesterase (ChE) genotypes were measured by dibucaine inhibition in vitro. The distributions of ChE surrounded the blood vessels and nerve fibers in lung or pancreas tissues were detected by immunohistochemical staining and indirect immunofluorescence. Serum lactic acid, ammonia and other clinical data were analyzed. Serum ChE in patients with acetyl cholinesterase deficiency were only 1/50 to 1/1000 fold of normal controls. Comparing to controls, dibucaine inhibition values of patients were significantly lower, while there were no differences in red blood cells acetyl cholinesterase. Serum lactic acid and ammonia in patients were significantly higher than controls. Inser 1281-1282 GC of COLQ gene was found in 2 patients, while IVS 6 + 21 T > A, IVS 6 + 30 G > T, IVS 6 + 34 T > C and IVS66 + 12 inser T mutations were found in the other 4 patients, respectively. In addition, the patients with COLQ gene mutation were resistant to regular doses of anesthetics. COLQ gene mutation may be an important reason for the lack of serum ChE in patients with acetyl cholinesterase deficiency.
Subject(s)
Acetylcholinesterase/deficiency , Collagen/genetics , Metabolism, Inborn Errors/genetics , Muscle Proteins/genetics , Mutation , Acetylcholinesterase/blood , Acetylcholinesterase/genetics , Humans , Lung/enzymology , Lung/pathology , Metabolism, Inborn Errors/blood , Metabolism, Inborn Errors/pathology , Pancreas/enzymology , Pancreas/pathologyABSTRACT
Stem cells and gene therapy have become promising strategies for treating ischemic diseases and regenerating tissue. Hepatocyte growth factor (HGF) is an angiogenic growth factor with multiple functions, including promoting angiogenesis, regulating inflammation, inhibiting fibrosis, and activating tissue regeneration. Numerous preclinical experiments and clinical trials have demonstrated the feasibility and efficacy of HGF gene therapy in the treatment of ischemic diseases and tissue regeneration. This review summarizes the current advances of therapeutic angiogenesis using HGF gene transfer and modified stem cells. The physiological roles of HGF in angiogenesis and tissue regeneration are revisited. The current advances of clinical trials of plasmid and adenovirus HGF in the treatment of critical limb ischemia and coronary heart disease in China are introduced. Furthermore, valuable insight is provided into the prospective future of novel regenerative strategies using HGF-modified mesenchymal stem cells. HGF gene therapy is presented as a promising therapeutic approach in the treatment of ischemic diseases and regenerative medicine.
Subject(s)
Coronary Disease/therapy , Genetic Therapy/trends , Hepatocyte Growth Factor/therapeutic use , Ischemia/therapy , China , Coronary Disease/genetics , Hepatocyte Growth Factor/genetics , Humans , Ischemia/genetics , Regeneration/genetics , Regenerative Medicine/trendsABSTRACT
A novel glucoside bletilloside A (1) was isolated from the tubers of Bletilla striata, together with seven known compounds (2-8). Their structures were determined on the basis of extensive spectroscopic analyses. All compounds were evaluated for the inhibition on NO production effects in RAW 264.7 macrophage cells, while militarine (4) and dactylorhin A (5) exhibited moderate inhibitory effects.
Subject(s)
Bibenzyls/isolation & purification , Bibenzyls/pharmacology , Glucosides/isolation & purification , Glucosides/pharmacology , Orchidaceae/chemistry , Animals , Bibenzyls/chemistry , Glucosides/chemistry , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Mice , Molecular Structure , Nitric Oxide/biosynthesis , Plant Tubers/chemistryABSTRACT
An Affi-Prep Polymyxin column was combined with a Phenyl Sepharose column and a Sephacryl S-300 column, respectively, to remove the lipopolysaccharides(LPS) in the anti-complementary crude polysaccharides of Houttuynia Herba. The contents of LPS in the polysaccharides were determined by chromogenic tachypleus amebocyte lysate(TAL)method during the procedure of purifying. The anti-complementary activities of the polysaccharides were also compared before and after the removal of LPS. Less remanent LPS was detected after purified using Penyl Sepharose combined with polymyxin column, with the clearance rate of 42.85%. All the columns had no effect on the anti-complementary activity of the polysaccharides. Penyl Sepharose combined with polymyxin column would be sound for LPS removal of the anti-complementary polysaccharides without reducing their bioactivity.
Subject(s)
Houttuynia/chemistry , Lipopolysaccharides/isolation & purification , Polysaccharides/chemistry , Chromatography , SepharoseABSTRACT
PURPOSE: To investigate effects of neuro-immuno-modulation on wound healing by observing changes of cytokines and hypothalamic-pituitary-adrenal (HPA) axis hormones in acute stress reaction in rats with wound and combined local radiation injury. METHODS: Sixty female Wistar rats (weighting 200 ± 20 g) were randomly divided into normal control group, wound group and combined wound-local radiation (CWR) group (25 Gy local radiation post wound), 20 rats in each group. Contents of IL-1ß, IL-6 and IFN-γ and IL-4 in serum were measured and changes of adrenocorticotropic hormone (ACTH) and glucocorticoid (GC) in serum were analyzed by using enzyme-linked immunosorbent assay and radioimmunologic assay, respectively at different time points post wound and radiation. RESULTS: (1) The level of IFN-γ, one of the Th1 cell cytokines increased significantly at 14 d post CWR, which was markedly higher than that in control group and wound group. However, the level of IL-4, IL-1ß and IL-6, one of the Th2 cell cytokines, did not show obvious change. (2) Ratio of Th1/Th2 (IFN-γ/IL-4) in wound group and CWR group increased significantly at 7 d after wound and radiation, which suggested that Th1/Th2 balance drifted to Th1 immune response. The ratio of Th1/Th2 in wound group returned to the normal level up to 14 d after the wound and radiation, while the Th1/Th2 ratio in CWR group increased persistently and was much higher than that in control and wound groups. (3) Level of serous ACTH and GC in CWR group increased at 3 d post wound and radiation, and among them, level of GC showed statistically significant increase, which was much higher than that in control and wound groups. CONCLUSION: Level of serous neurohormone GC in rats increased significantly immediately after wound and radiation; while the level of IFN-γ showed significant increase only up to 14 d after wound and radiation, and the Th1/Th2 imbalance sustained till 28 d post wound and radiation. In order to reduce acute damage caused by CWR, organic immune system and nerve system showed up a marked regulate effects simultaneously and mutually. Nonetheless, the excessive stress induced by CWR causes disturbance of immunoregulation, which is one of the key reasons for delayed wound healing in CWR.
Subject(s)
Radiation Injuries/immunology , Wound Healing , Adrenocorticotropic Hormone/blood , Animals , Cytokines/blood , Female , Glucocorticoids/blood , Humans , Rats , Rats, Wistar , Th1 Cells/immunology , Th2 Cells/immunologyABSTRACT
Neuroticism is the most common vulnerability factor of depression. However, the mechanism underlying this vulnerability is still unclear. Previous studies suggested that rumination intensifies the negative effect of neuroticism on depression. However, whether cognitive control could explain the association between neuroticism and depression remains unclear to date. Therefore, this study evaluated the indirect effects of rumination and thought control on the relationship between neuroticism and depression. Seven self-report measures were employed among healthy and main depression disorder (MDD) participants. Three studies were used to examine the hypotheses. Results of the three studies showed significant correlations among neuroticism, rumination, thought control, and depression. Rumination mediated the link between neuroticism and depression among healthy young adults, and this finding replicated previous studies. This study provided new evidence that thought control mediates the association between neuroticism and depression in both healthy and MDD populations. In conclusion, rumination increases neuroticism risk for depression, but high-level thought control decreases the effect of neuroticism on depression. This study may serve as a reference to develop effective and focused interventions for MDD patients.
ABSTRACT
AIM: To investigate the pharmacological effect of TongXie-YaoFang (TXYF) formula, a Chinese herbal formula, on Diarrhea-predominant irritable bowel syndrome (D-IBS) rats. METHODS: In a neonatal maternal separation plus restraint stress (NMS + RS) model of D-IBS, male Sprague Dawley rats were randomly divided into two groups (NMS + RS group and TXYF-formula group) with no handlings were used as controls (NH group). Starting from postnatal day 60, rats in TXYF-formula group were administered TXYF-formula (4.92 g/100 g bodyweight) orally twice a day for 14 consecutive days while NH group and NMS + RS group were given distilled water. Using short-circuit current technology, we observed 5-HT-induced changes of current across ion channels, such as cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel, epithelial Na+ channel (ENaC), Ca2+-dependent Cl- channel (CACC), Na+-K+-2Cl- co-transporter (NKCC), and Na+-HCO3- co-transporter (NBC), in the colonic epithelium of three groups after exposure to drugs and specific blockers with a Power Lab System (AD Instruments International). RESULTS: Under basal conditions, the changes of short-circuit current (∆Isc, µA/cm2) induced by 5-HT were similar in NH group and TXYF-formula group, and both higher than NMS + RS group (70.86 µA/cm2 ± 12.32 µA/cm2, 67.67 µA/cm2 ± 11.68 µA/cm2vs 38.8 µA/cm2 ± 7.25 µA/cm2, P < 0.01, respectively). When CACC was blocked by 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid, 5-HT-induced ∆Isc was smaller in NMS + RS group than in NH group and TXYF-formula group, respectively (48.41 µA/cm2 ± 13.15 µA/cm2vs 74.62 µA/cm2 ± 10.73 µA/cm2, 69.22 µA/cm2 ± 11.7 µA/cm2, P < 0.05, respectively). The similar result could be obtained when ENaC was blocked by Amiloride (44.69 µA/cm2 ± 12.58 µA/cm2vs 62.05 µA/cm2 ± 11.26 µA/cm2, 62.11 µA/cm2 ± 12.01 µA/cm2, P < 0.05, respectively). However, when CFTR Cl- channel was blocked by 1,1-dimethyl piperidinium chloride (DPC), 5-HT-induced ∆Isc did not significantly differ in three groups (42.28 µA/cm2 ± 10.61 µA/cm2vs 51.48 µA/cm2 ± 6.56 µA/cm2vs 47.75 µA/cm2 ± 7.99 µA/cm2, P > 0.05, respectively). The similar results could also be obtained in three groups when NBC and NKCC were respectively blocked by their blockers. CONCLUSION: TXYF-formula can regulate the Cl- and HCO3- secretion of colonic mucosa via CFTR Cl- channel, Cl-/HCO3- exchanger, NBC and NKCC co-transporters.
Subject(s)
Chloride Channels/drug effects , Diarrhea/metabolism , Drugs, Chinese Herbal/pharmacology , Intestinal Mucosa/drug effects , Irritable Bowel Syndrome/metabolism , Sodium-Bicarbonate Symporters/drug effects , 5-Hydroxytryptophan/pharmacology , Adult , Amiloride/pharmacology , Animals , Chloride Channels/antagonists & inhibitors , Colon/metabolism , Diarrhea/drug therapy , Diarrhea/etiology , Epithelial Sodium Channel Blockers/pharmacology , Humans , Intestinal Mucosa/metabolism , Irritable Bowel Syndrome/drug therapy , Irritable Bowel Syndrome/etiology , Male , Maternal Deprivation , Piperidines/pharmacology , Random Allocation , Rats , Rats, Sprague-Dawley , Sodium Potassium Chloride Symporter Inhibitors/pharmacology , Sodium-Bicarbonate Symporters/antagonists & inhibitors , Sodium-Potassium-Chloride Symporters/drug effects , Stress, Psychological/complications , Young AdultABSTRACT
There have been many structural and functional imaging studies of creative thinking, but combining structural and functional magnetic resonance imaging (MRI) investigations with respect to creative thinking is still lacking. Thus, the aim of the present study was to explore the associations among inter-individual verbal creative thinking and both regional homogeneity and cortical morphology of the brain surface. We related the local functional homogeneity of spontaneous brain activity to verbal creative thinking and its dimensions--fluency, originality, and flexibility--by examining these inter-individual differences in a large sample of 268 healthy college students. Results revealed that people with high verbal creative ability and high scores for the three dimensions of creativity exhibited lower regional functional homogeneity in the right precuneus. Both cortical volume and thickness of the right precuneus were positively associated with individual verbal creativity and its dimensions. Moreover, originality was negatively correlated with functional homogeneity in the left superior frontal gyrus and positively correlated with functional homogeneity in the right occipito-temporal gyrus. In contrast, flexibility was positively correlated with functional homogeneity in the left superior and middle occipital gyrus. These findings provide additional evidence of a link between verbal creative thinking and brain structure in the right precuneus--a region involved in internally--focused attention and effective semantic retrieval-and further suggest that local functional homogeneity of verbal creative thinking has neurobiological relevance that is likely based on anatomical substrates.
Subject(s)
Creativity , Individuality , Parietal Lobe/physiology , Thinking/physiology , Verbal Behavior/physiology , Adolescent , Adult , Dominance, Cerebral , Female , Humans , Male , Young AdultABSTRACT
Help seeking (HS) is a core coping strategy that is directed towards obtaining support, advice, or assistance as means of managing stress. Women have been found to use more HS than men. Neural correlates of sex differences have also been reported in prefrontal-limbic system (PLS) regions that are linked to stress and coping, yet structural differences between men and women relating to HS in the PLS are still unknown. Thus, the association between gray matter volume (GMV) and HS was investigated using voxel-based morphometry (VBM) in a large healthy sample (126 men and 156 women). Results indicated women reported more HS than men did. VBM results showed that the relation between HS scores and GMV differed between men and women in regions of the bilateral orbitofrontal cortex extending to the subgenual anterior cingulate cortex(OFC/sgACC). Among women, higher HS scores were associated with smaller GMV in these areas while a positive correlation between GMV and HS scores was observed among men. These results remained significant after controlling for general intelligence, stress, anxiety and depression. Thus, this study suggested that structural differences between men and women are correlated to characteristic brain regions known to be involved in the PLS which is considered critical in stress regulation.
Subject(s)
Adaptation, Psychological , Gyrus Cinguli/pathology , Hippocampus/pathology , Prefrontal Cortex/pathology , Stress, Psychological/pathology , Adolescent , Adult , Female , Humans , Male , Neuroimaging , Sex Characteristics , Stress, Psychological/psychology , Young AdultABSTRACT
MYB transcription factors play important roles in the regulation of plant growth, developmental metabolism and stress responses. In this study, a new MYB transcription factor gene, GmMYBJ1, was isolated from soybean [Glycine max (L.)]. The GmMYBJ1 cDNA is 1296bp in length with an open reading frame (ORF) of 816 bp encoding for 271 amino acids. The amino acid sequence displays similarities to the typical R2R3 MYB proteins reported in other plants. Transient expression analysis using the GmMYBJ1-GFP fusion gene in onion epidermal cells revealed that the GmMYBJ1 protein is targeted to the nucleus. Quantitative RT-PCR analysis demonstrated that GmMYBJ1 expression was induced by abiotic stresses, such as drought, cold, salt and exogenous abscisic acid (ABA). Compared to wild-type (WT) plants, transgenic Arabidopsis overexpressing GmMYBJ1 exhibited an enhanced tolerance to drought and cold stresses. These results indicate that GmMYBJ1 has the potential to be utilized in transgenic breeding lines to improve abiotic stress tolerance.