Objective:To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). Methods:From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. This study was approved by the Medical Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University(Ethics No. 2023-056). Results:Compared with the HC group, the BD-Ⅰ patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex( P<0.05). A significant interaction between the CACNA1C genotype and the cortical thickness(HC vs.BD) of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted( P<0.05). Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex( P<0.05), and right superior temporal cortex predominantly among carriers of the BD-Ⅰ G allele. Conclusion:The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Objective:To investigate the alteration of glymphatic system based on diffusion tensor image-analysis along the perivascular space(DTI-ALPS)in bipolar disorder Ⅰ(BD-Ⅰ).Methods:A total of 44 BD-Ⅰ patients(BD-Ⅰ group) admitted to the Affiliated Brain Hospital of Guangzhou Medical University from January 2012 to December 2017 were selected.In addition, totally 30 healthy controls (HC group) were recruited. The diffusion tensor image data were analyzed retrospectively, and along the perivascular space (ALPS) index was calculated. Hamilton anxiety scale (HAMA), 17-item Hamilton depression rating scale (HAMD-17), Young mania rating scale (YMRS) and global assessment function (GAF) were used to evaluate the severity of anxiety, depression, mania and social function respectively. SPSS 25.0 software was used for t-test, Z-test and chi-square test, and the differences in clinical data and DTI-ALPS index between the two groups were compared. The partial correlation test was used to analyze the correlations between DTI-ALPS index and the clinical indicators such as HAMA, HAMD-17, YMRS and GAF. Results:The DTI-ALPS indexes in left(1.69±0.17), right(1.44±0.15) and bilateral cerebral hemispheres(1.56±0.15) of BD-Ⅰ group were lower than those in HC group ((1.71±0.15), (1.46±0.13) and (1.58±0.12)), but the differences were not statistically significant ( t=-0.441, -0.545, -0.556, all P>0.05). After controlling for gender, age, years of education and course of disease, there were significant negative correlations between bilateral average DTI-ALPS index and somatic anxiety ( r=-0.334, P=0.038), as well as between right DTI-ALPS index and somatic anxiety( r=-0.349, P=0.030) in BD-Ⅰ group. Conclusion:The dysfunction of cerebral glymphatic system is not obvious in BD-Ⅰ patients, but their anxiety may be related to dysfunction cerebral glymphatic system.

Objective:To investigate the related genes, signaling pathways and possible mechanisms of malignant transformation of human papillomavirus type 16 (HPV-16) immortalized cervical epithelial cell line H8.Methods:The malignant transformed H8 cell model was constructed, and the changes of cell invasion ability and cell migration ability of H8 cells after malignant transformation were detected by Transwell assay, and the changes of clone formation ability of H8 cells after malignant transformation were detected by plate clone formation assay. Total RNA was extracted from malignant transformed H8 cells and H8 cells, and the two groups of cells were sequenced by transcriptome using Illumina novaseq 6000 sequencing platform, differentially expressed genes (DEGs) were identified and analyzed, and Gene Ontology (GO) function enrichment analysis, Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment analysis and protein-protein interaction were performed.Results:The invasion ability, migration ability and clone formation ability of malignant transformed H8 cells significantly increased as compared to H8 cells. A total of 203 differentially expressed genes were identified in H8 cells before and after malignant transformation, of which 98 were up-regulated and 105 down-regulated. GO enrichment analysis showed that DEGs were mainly involved in biological processes such as cellular processes, biological regulation, and metabolic processes. KEGG pathway enrichment analysis showed that DEGs were mainly enriched in alanine, aspartate and glutamate metabolic pathway, glycine, serine and threonine metabolism pathway, p53 signaling pathway and TGF-β signaling pathway, PI3K-Akt signaling pathway. PPI analysis screened 10 hub genes including DDIT3, TRIB3 and ASNS.Conclusions:Compared with H8 cells, malignant transformed H8 cells have a large number of differentially expressed genes and pathways at the transcriptional level, which could further provide new ideas for the mechanism of malignant transformation and carcinogenesis as well as finding new targets for the prevention of malignant transformation.

Aging-elevated DNMT3A R882H-driven clonal hematopoiesis (CH) is a risk factor for myeloid malignancies remission and overall survival. Although some studies were conducted to investigate this phenomenon, the exact mechanism is still under debate. In this study, we observed that DNMT3A R878H bone marrow cells (human allele: DNMT3A R882H) displayed enhanced reconstitution capacity in aged bone marrow milieu and upon inflammatory insult. DNMT3A R878H protects hematopoietic stem and progenitor cells from the damage induced by chronic inflammation, especially TNFα insults. Mechanistically, we identified that RIPK1-RIPK3-MLKL-mediated necroptosis signaling was compromised in R878H cells in response to proliferation stress and TNFα insults. Briefly, we elucidated the molecular mechanism driving DNMT3A R878H-based clonal hematopoiesis, which raises clinical value for treating DNMT3A R882H-driven clonal hematopoiesis and myeloid malignancies with aging.

Objective:To compare the value of Caprini, Padua and Autar risk assessment models in the risk assessment of venous thromboembolism in hospitalized stroke patients.Methods:A retrospective case-control study were used to collect hospitalized stroke patients in the neurology department of Xiangya Hospital from January 1, 2018 to June 30, 2020. 75 patients with venous thromboembolism (VTE) were VTE group and 75 patients without VTE were control group. The risk of thrombosis was assessed by Caprini risk assessment model, Padua risk assessment model and Autar risk assessment model respectively. The predictive value of each model on the risk of VTE formation in stroke patients was analyzed by receiver operating characteristic (ROC) curve and area under the curve (AUC).Results:The areas under the curve of Caprini, Padua and Autar risk assessment models for predicting the risk of VTE formation in stroke patients were 0.768±0.039, 0.746±0.040 and 0.710±0.042 respectively. The sensitivity, specificity and accuracy were 81.3%, 61.3%, 71.3%(Caprini), 72.0%, 72.0%, 72.0%(Padua), 66.7%, 68.0% and 67.3%(Autar) respectively. There was no significant difference in the prediction value of the three models on the formation risk of stroke VTE (all P>0.05). The technique for order preference by similarity to ideal solution (TOPSIS) method was used to comprehensively evaluate the AUC, sensitivity, specificity and accuracy of the three risk assessment models. Padua risk assessment model was the best, followed by Caprini risk assessment model and Autar risk assessment model. Conclusions:The Caprini, Padua, and Autar risk assessment scales can well predict the risk of VTE in stroke patients. The Caprini scale has the highest sensitivity and the Padua scale has the highest specificity. There is no significant difference in the predictive value of the three scales. Comprehensive evaluation of predictive value: Padua risk assessment scale is the best.

Objective:To investigate the psychology status and quality of life in patients with inflammatory bowel disease(IBD) in China, and to analyze the influencing factors.Methods:From September 2021 to May 2022, 42 hospitals in 22 provinces(autonomous regions and municipalities directly under the central government) in China, the clinical data of 2 478 IBD patients were collected, which included age, gender, weight, first visit or not, disease activity, disease course, main clinical manifestations(diarrhea, abdominal pain, hematochezia, extraintestinal manifestations), complications, treatment medication(5-aminosalicylic acid, glucocorticoids, immunosuppressive agents, and biological agents), and whether to have surgery. Anxiety, depression, sleep quality and quality of life of IBD patients were evaluated by generalized anxiety disorder-7 items, patient health questionnaire-9 items, Pittsburgh sleep quality index and inflammatory bowel disease questionnaire, and the related influencing factors were analyzed. Univariate analysis and multiple linear regression analysis were used for statistical analysis.Results:The average age of 2 478 IBD patients was 37.96 years old, and male counted for 62.43%(1 547/2 478). There were 61.82%(1 532/2 478) of the IBD patients in the active stage of disease, mostly mild or moderate(588 and 734 cases). There were 60.61%(1 502/2 478) of the IBD patients with different degrees of anxiety, 58.35%(1 446/2 478) of the IBD patients with different degrees of depression, and 48.87%(1 211/2 478) of the IBD patients had different degrees of sleep problems. The results of multiple linear regression analysis indicated that female, higher level of disease activity and longer disease course were independent risk factors of anxiety, depression and sleep quality in the IBD patients(unstandardized regression coefficient(95% confidence interval) 1.08(0.65 to 1.50), 0.45(0.23 to 0.68), 0.19(0.02 to 0.36), 0.83(0.33 to 1.32), 0.62(0.36 to 0.88), 0.28(0.08 to 0.47), 0.47(0.16 to 0.77), 0.39(0.23 to 0.55), 0.14(0.02 to 0.26); P<0.001, <0.001, =0.025 , =0.001, <0.001, =0.005, =0.003, <0.001, =0.027). The usage of biological agents was an independent protective factor of anxiety(unstandardized regression coefficient(95% confidence interval) -0.67(-1.17 to -0.17), P=0.008), and older age was an independent risk factor of sleep quality(unstandardized regression coefficient(95% confidence interval) 0.35(0.09 to 0.61), P=0.008). Higher level of disease activity, symptoms of diarrhea, abdominal pain, presence of extraintestinal manifestations, usage of 5-aminosalicylic acid and glucocorticoid, and with surgical treatment were independent risk factors of quality of life(unstandardized regression coefficient(95% confidence interval) -11.00(-12.24 to -9.76), -2.90(-5.26 to -0.55), -3.93(-6.25 to -1.61), -5.79(-9.87 to -1.71), -4.78(-7.79 to -1.76), -7.71(-11.07 to -4.35), -4.37(-8.00 to -0.73); P<0.001, =0.016, =0.001, =0.005 , =0.002, <0.001, =0.019), while the usage of biological agents was an independent protective factor of quality of life (unstandardized regression coefficient(95% confidence interval) 4.72(1.97 to 7.48), P=0.001). Conclusion:IBD patients generally have different degrees of anxiety, depression and sleep problems, which affect the quality of life of patients. Gender, disease activity and disease course are the influencing factors of mental disorders in IBD patients.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD) that has become a major gastroenterologic problem during recent decades. Numerous complicating factors are involved in UC development such as oxidative stress, inflammation, and microbiota disorder. These factors exacerbate damage to the intestinal mucosal barrier. Spirulina platensis is a commercial alga with various biological activity that is widely used as a functional ingredient in food and beverage products. However, there have been few studies on the treatment of UC using S. platensis aqueous extracts (SP), and the underlying mechanism of action of SP against UC has not yet been elucidated. Herein, we aimed to investigate the modulatory effect of SP on microbiota disorders in UC mice and clarify the underlying mechanisms by which SP alleviates damage to the intestinal mucosal barrier. Dextran sulfate sodium (DSS) was used to establish a normal human colonic epithelial cell (NCM460) injury model and UC animal model. The mitochondrial membrane potential assay 3-‍‍(4,5-dimethylthiazol-2-yl)-2,‍5-diphenyltetrazolium bromide (MTT) and staining with Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) and Hoechst 33258 were carried out to determine the effects of SP on the NCM460 cell injury model. Moreover, hematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qPCR), western blot, and 16S ribosomal DNA (rDNA) sequencing were used to explore the effects and underlying mechanisms of action of SP on UC in C57BL/6 mice. In vitro studies showed that SP alleviated DSS-induced NCM460 cell injury. SP also significantly reduced the excessive generation of intracellular reactive oxygen species (ROS) and prevented mitochondrial membrane potential reduction after DSS challenge. In vivo studies indicated that SP administration could alleviate the severity of DSS-induced colonic mucosal damage compared with the control group. Inhibition of inflammation and oxidative stress was associated with increases in the activity of antioxidant enzymes and the expression of tight junction proteins (TJs) post-SP treatment. SP improved gut microbiota disorder mainly by increasing antioxidant enzyme activity and the expression of TJs in the colon. Our findings demonstrate that the protective effect of SP against UC is based on its inhibition of pro-inflammatory cytokine overproduction, inhibition of DSS-induced ROS production, and enhanced expression of antioxidant enzymes and TJs in the colonic mucosal barrier.
Animals ; Antioxidants/pharmacology* ; Colitis/prevention & control* ; Colitis, Ulcerative/metabolism* ; Colon/metabolism* ; Dextran Sulfate/toxicity* ; Disease Models, Animal ; Gastrointestinal Microbiome ; Inflammation/metabolism* ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; Spirulina

Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD) that has become a major gastroenterologic problem during recent decades. Numerous complicating factors are involved in UC development such as oxidative stress, inflammation, and microbiota disorder. These factors exacerbate damage to the intestinal mucosal barrier. Spirulina platensis is a commercial alga with various biological activity that is widely used as a functional ingredient in food and beverage products. However, there have been few studies on the treatment of UC using S. platensis aqueous extracts (SP), and the underlying mechanism of action of SP against UC has not yet been elucidated. Herein, we aimed to investigate the modulatory effect of SP on microbiota disorders in UC mice and clarify the underlying mechanisms by which SP alleviates damage to the intestinal mucosal barrier. Dextran sulfate sodium (DSS) was used to establish a normal human colonic epithelial cell (NCM460) injury model and UC animal model. The mitochondrial membrane potential assay 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and staining with Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) and Hoechst 33258 were carried out to determine the effects of SP on the NCM460 cell injury model. Moreover, hematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qPCR), western blot, and 16S ribosomal DNA (rDNA) sequencing were used to explore the effects and underlying mechanisms of action of SP on UC in C57BL/6 mice. In vitro studies showed that SP alleviated DSS-induced NCM460 cell injury. SP also significantly reduced the excessive generation of intracellular reactive oxygen species (ROS) and prevented mitochondrial membrane potential reduction after DSS challenge. In vivo studies indicated that SP administration could alleviate the severity of DSS-induced colonic mucosal damage compared with the control group. Inhibition of inflammation and oxidative stress was associated with increases in the activity of antioxidant enzymes and the expression of tight junction proteins (TJs) post-SP treatment. SP improved gut microbiota disorder mainly by increasing antioxidant enzyme activity and the expression of TJs in the colon. Our findings demonstrate that the protective effect of SP against UC is based on its inhibition of pro-inflammatory cytokine overproduction, inhibition of DSS-induced ROS production, and enhanced expression of antioxidant enzymes and TJs in the colonic mucosal barrier.

Objective To investigate the accuracy of body mass index (BMI) as the evaluation standard for obesity in Miao adults in Guangxi, to find out the BMI cutoff value suitable for the evaluation standard of adult obesity, and to provide an accurate and reliable reference value for the prevention and treatment of obesity in Miao nationality adults. Methods Using a cross-sectional design, residents aged 18 years or older in the Miao villages in Rongshui Miao Autonomous County, Guangxi, were selected as the research subjects, and their body composition was measured. The percent body fat (PBF) standard was used as the ^“gold standard^” for obesity, and the BMI standard for obesity in Chinese adults was used as the positive screening standard. The accuracy of the BMI standard was evaluated, and the ROC curve analysis was used to determine the optimal BMI cutoff value for obesity in Miao adults. Results The detection rate of obesity of Miao adults in Guangxi by BMI method was lower than that by PBF method (10.3% vs 19.0%, χ²=426.62, P<0.001). The results of reliability evaluation showed that BMI was in good agreement with PBF in judging obesity (Kappa=0.59, P<0.001). BMI as a screening criterion for obesity in Miao adults showed high specificity and low sensitivity, low Yordon index, high positive predictive value and high positive likelihood ratio, and low negative predictive value and high negative likelihood ratio. When the PBF was used as the ^“gold standard^”, BMI had a good diagnostic performance for obesity in Miao adults (AUC=0.959, P<0.001). The optimal BMI cutoff points for obesity in adults of Miao nationality in Guangxi were 25.85 kg/m² and 25.55 kg/m² for men and women, respectively. Conclusion BMI is of great value for the diagnosis of obesity in Miao adults, but it should not be used as an exclusion criterion for obesity. Especially in the case of a small sample size, the risk of misclassification bias is relatively high.

Objective:To investigate the effect of pterostilbene on the growth, apoptosis and autophagy of a human papillomavirus type 16 (HPV-16) -immortalized cervical epithelial cell line H8.Methods:H8 cells were treated with pterostilbene at different concentrations of 0 (control group) , 25, 50, 75, 100 μmol/L for 24 and 48 hours. Cell counting kit-8 (CCK8) assay was performed to evaluate the cellular proliferative activity, flow cytometry was conducted to detect apoptosis and cell cycle, monodansylcadaverine (MDC) staining and fluorescence microscopy were performed to detect autophagy, and Western blot analysis was conducted to determine the expression of the cell cycle-related protein cyclinD1, apoptosis-related proteins caspase-3 and caspase-9, autophagy-related proteins Beclin1, microtubule-associated protein 1 light chain 3 (LC3) -Ⅱ/Ⅰ, ATG5 and P62, as well as HPV oncoproteins E6 and E7. Statistical analysis was carried out by using one-way analysis of variance, repeated measures analysis of variance and least significant difference- t test. Results:After 48-hour treatment with pterostilbene at different concentrations of 0, 25, 50, 75, 100 μmol/L, the relative cellular proliferation rate significantly differed among the groups (100.00% ± 1.56%, 99.02% ± 4.97%, 93.59% ± 2.01%, 81.28% ± 4.90%, 69.17% ± 7.56%, respectively; F = 77.22, P < 0.05) , and gradually decreased along with the increase in the concentration of pterostilbene; compared with the control group, the pterostilbene groups all showed significantly decreased cellular proliferation rate (all P < 0.05) . After 24-hour treatment with pterostilbene, the proportions of H8 cells at G1, G2 and S phases significantly differed among the above groups ( F = 7 845.00, 51.14, 266.50, respectively, all P < 0.05) ; compared with the control group, the pterostilbene groups showed significantly increased proportions of H8 cells at G1 and G2 phases (all P < 0.05) , but significantly decreased proportions of H8 cells at S phase ( P < 0.05) . After 48-hour treatment with pterostilbene, the apoptosis rate was significantly higher in the 25-, 50-, 75- and 100-μmol/L pterostilbene groups (14.66% ± 0.22%, 13.50% ± 0.49%, 14.56% ± 0.19%, 15.30% ± 0.76%, respectively) than in the control group (11.58% ± 0.50%, all P < 0.05) . After 24-hour treatment with pterostilbene, MDC staining showed only a small number of H8 cells with bright dot-like fluorescence in the control group, but increased number of autophagosome-positive H8 cells with bright dot-like fluorescence in the pterostilbene groups. Western blot analysis revealed that there were significant differences in the protein expression of cyclin D1, caspase-3, caspase-9, Beclin1, LC3-Ⅱ/Ⅰ, ATG5, P62, E6 and E7 among the control and pterostilbene groups after 24- and 48-hour treatment with pterostilbene (all P < 0.05) . The treatment with pterostilbene could down-regulate the expression of cyclin D1, E6 and E7, and up-regulate the expression of caspase-3, caspase-9, Beclin1, LC3-Ⅱ/Ⅰ, ATG5 and P62, with significant differences between the control group and most pterostilbene groups in expression of the above proteins (all P < 0.05) . Conclusion:Pterostilbene can inhibit the proliferation of H8 cells, promote their apoptosis and autophagy, and down-regulate the expression of oncogenes E6 and E7.