A 58-year-old female patient presented with red papules, plaques, and scabs on her right foot accompanied by pain and itching for 14 years. Dermatological examination revealed extensive red plaques on her right foot and ankle, with scattered red papules in between; some of the plaques were covered with a moderate amount of yellow-brown crusts, and a small amount of yellow exudate was observed at the junction of the toes and the dorsum of the foot. Histopathological examination of the skin lesions showed hyperkeratosis, parakeratosis, pseudoepitheliomatous hyperplasia, neutrophil aggregation in the epidermis, and mixed inflammatory cell infiltration in the dermis. Three different types of colonies were cultured from the skin lesion tissues: light brown granular colonies, black granular colonies, and white-brown filamentous colonies. Under the microscope, the filamentous colonies appeared as long chains of brown conidia with short cylindrical beaks, while the black and light brown granular colonies appeared as clusters of spores, with single or multiple septa inside, and some budding spores were observed. Electron microscopy further confirmed the above structures. Molecular biological analysis revealed that the three types of colonies were all identified as Alternaria alternata. The patient was diagnosed with cutaneous alternariosis caused by Alternaria alternata with special morphology. After 7 months of treatment with oral itraconazole, the skin lesions healed, and no recurrence was observed during a 3-year follow-up.

Objective:To investigate changes in behavior and hippocampal and prefrontal cortical myelin basic protein(MBP) in model mice with post-traumatic stress disorder(PTSD).Methods:Thirty-two clean-grade male C57BL/6J mice were randomly divided into control group, PTSD 3 d group, PTSD 7 d group and PTSD 14 d group based on matching body mass, with 8 mice in each group. The mice in PTSD 3 d, 7 d and 14 d groups were decapitated at 3 d, 7 d, and 14 d after modeling.The PTSD mouse model was established through conditioned foot shock and single prolonged stress. Anxious- and depressive-like behaviors of mice were assessed by the open field test(OFT). The mouse step-through passive avoidance experiment was used for electric shock training and learning and memory retention. Myelin morphology alterations in the hippocampus and prefrontal cortex of the mouse were examined via myelin staining.The expression levels of MBP were quantified using Western blot and immunohistochemical staining techniques. All experimental data were analyzed and visualized using GraphPad Prism 8.0.2 and SPSS 25.0, the multi groups comparison of behavioral and molecular indicator data was conducted by one-way ANOVA, and the correlation between MBP relative protein expression level and behavioral indicators was analyzed by Pearson correlation analysis.Results:(1) Behavioral results: in OFT, there were significant differences in total distance, average speed, time of stationary and times of entering the central area among all groups( F=16.72, 16.74, 7.37, 5.93, all P<0.05).The total distance and the average speed time of PTSD 3 d, 7 d, 14 d group were all lower than those in control group(all P<0.05).In the mouse step-through passive avoidance experiment, significant differences were observed across all groups in terms of total distance traveled, average speed, dark box entries, and activity time( F=52.78, 55.47, 9.07, 24.88, all P<0.05).All the indexes of PTSD 3 d group and PTSD 7 d group were all higher than those in control group and PTSD 14 d group(all P<0.05).(2)Myelin staining revealed statistically significant differences in the myelin staining areas of the hippocampal CA1 region and the prefrontal cortex across all groups( F=6.67, 5.77, all P<0.05). The stained myelin area in the CA1 region of the hippocampus in the PTSD 3 d group((123.30±11.62)μm 2)was significantly lower compared to the control group((153.00±2.61)μm 2)( P<0.05). The stained myelin area in the prefrontal cortex of the PTSD 3 d group((119.50±9.26)μm 2)was significantly lower compared to that in the control group((154.80±12.40)μm 2)( P<0.05). (3) Western blot results demonstrated significant variations in the expression levels of myelin basic protein (MBP) within the hippocampus and prefrontal cortex across all experimental groups ( F=10.15, 5.28, all P<0.05). The expression levels of MBP in the hippocampal tissue of the PTSD 3 d group (0.89±0.07), PTSD 7 d group (0.90±0.14), and PTSD 14 d group (0.85±0.13) were significantly lower compared to those in the control group(1.17±0.02)(all P<0.05). The expression levels of MBP protein in the prefrontal cortex of the PTSD 3 d group(0.73±0.16) and PTSD 7 d group (0.70±0.12)were significantly lower compared to those in the control group (0.94±0.04)(all P<0.05). (4) Immunohistochemical staining revealed significant variations in the number of MBP-positive cells within the hippocampal CA1 region and the prefrontal cortex across all groups ( F=39.32, 21.81, both P<0.05). The quantity of MBP-positive cells in the hippocampal tissue of mice in the PTSD 3 d group((187.10±1.12)/mm 2)and PTSD 7 d group((193.10±2.18) /mm 2)was significantly reduced compared to the control group((204.80±3.25)/mm 2)(all P<0.05). The quantity of MBP-positive cells in the prefrontal cortex of the PTSD 7 d group((183.90±1.71)/mm 2) was significantly reduced compared to the control group((191.60±1.04) /mm 2)( P<0.05). Conclusion:The PTSD model mice showed anxious- and depression-like behavior, impaired learning and memory ability, and myelin damage in the hippocampus and prefrontal cortex.

Objective:To investigate changes in behavior and hippocampal and prefrontal cortical myelin basic protein(MBP) in model mice with post-traumatic stress disorder(PTSD).Methods:Thirty-two clean-grade male C57BL/6J mice were randomly divided into control group, PTSD 3 d group, PTSD 7 d group and PTSD 14 d group based on matching body mass, with 8 mice in each group. The mice in PTSD 3 d, 7 d and 14 d groups were decapitated at 3 d, 7 d, and 14 d after modeling.The PTSD mouse model was established through conditioned foot shock and single prolonged stress. Anxious- and depressive-like behaviors of mice were assessed by the open field test(OFT). The mouse step-through passive avoidance experiment was used for electric shock training and learning and memory retention. Myelin morphology alterations in the hippocampus and prefrontal cortex of the mouse were examined via myelin staining.The expression levels of MBP were quantified using Western blot and immunohistochemical staining techniques. All experimental data were analyzed and visualized using GraphPad Prism 8.0.2 and SPSS 25.0, the multi groups comparison of behavioral and molecular indicator data was conducted by one-way ANOVA, and the correlation between MBP relative protein expression level and behavioral indicators was analyzed by Pearson correlation analysis.Results:(1) Behavioral results: in OFT, there were significant differences in total distance, average speed, time of stationary and times of entering the central area among all groups( F=16.72, 16.74, 7.37, 5.93, all P<0.05).The total distance and the average speed time of PTSD 3 d, 7 d, 14 d group were all lower than those in control group(all P<0.05).In the mouse step-through passive avoidance experiment, significant differences were observed across all groups in terms of total distance traveled, average speed, dark box entries, and activity time( F=52.78, 55.47, 9.07, 24.88, all P<0.05).All the indexes of PTSD 3 d group and PTSD 7 d group were all higher than those in control group and PTSD 14 d group(all P<0.05).(2)Myelin staining revealed statistically significant differences in the myelin staining areas of the hippocampal CA1 region and the prefrontal cortex across all groups( F=6.67, 5.77, all P<0.05). The stained myelin area in the CA1 region of the hippocampus in the PTSD 3 d group((123.30±11.62)μm 2)was significantly lower compared to the control group((153.00±2.61)μm 2)( P<0.05). The stained myelin area in the prefrontal cortex of the PTSD 3 d group((119.50±9.26)μm 2)was significantly lower compared to that in the control group((154.80±12.40)μm 2)( P<0.05). (3) Western blot results demonstrated significant variations in the expression levels of myelin basic protein (MBP) within the hippocampus and prefrontal cortex across all experimental groups ( F=10.15, 5.28, all P<0.05). The expression levels of MBP in the hippocampal tissue of the PTSD 3 d group (0.89±0.07), PTSD 7 d group (0.90±0.14), and PTSD 14 d group (0.85±0.13) were significantly lower compared to those in the control group(1.17±0.02)(all P<0.05). The expression levels of MBP protein in the prefrontal cortex of the PTSD 3 d group(0.73±0.16) and PTSD 7 d group (0.70±0.12)were significantly lower compared to those in the control group (0.94±0.04)(all P<0.05). (4) Immunohistochemical staining revealed significant variations in the number of MBP-positive cells within the hippocampal CA1 region and the prefrontal cortex across all groups ( F=39.32, 21.81, both P<0.05). The quantity of MBP-positive cells in the hippocampal tissue of mice in the PTSD 3 d group((187.10±1.12)/mm 2)and PTSD 7 d group((193.10±2.18) /mm 2)was significantly reduced compared to the control group((204.80±3.25)/mm 2)(all P<0.05). The quantity of MBP-positive cells in the prefrontal cortex of the PTSD 7 d group((183.90±1.71)/mm 2) was significantly reduced compared to the control group((191.60±1.04) /mm 2)( P<0.05). Conclusion:The PTSD model mice showed anxious- and depression-like behavior, impaired learning and memory ability, and myelin damage in the hippocampus and prefrontal cortex.

A 58-year-old female patient presented with red papules, plaques, and scabs on her right foot accompanied by pain and itching for 14 years. Dermatological examination revealed extensive red plaques on her right foot and ankle, with scattered red papules in between; some of the plaques were covered with a moderate amount of yellow-brown crusts, and a small amount of yellow exudate was observed at the junction of the toes and the dorsum of the foot. Histopathological examination of the skin lesions showed hyperkeratosis, parakeratosis, pseudoepitheliomatous hyperplasia, neutrophil aggregation in the epidermis, and mixed inflammatory cell infiltration in the dermis. Three different types of colonies were cultured from the skin lesion tissues: light brown granular colonies, black granular colonies, and white-brown filamentous colonies. Under the microscope, the filamentous colonies appeared as long chains of brown conidia with short cylindrical beaks, while the black and light brown granular colonies appeared as clusters of spores, with single or multiple septa inside, and some budding spores were observed. Electron microscopy further confirmed the above structures. Molecular biological analysis revealed that the three types of colonies were all identified as Alternaria alternata. The patient was diagnosed with cutaneous alternariosis caused by Alternaria alternata with special morphology. After 7 months of treatment with oral itraconazole, the skin lesions healed, and no recurrence was observed during a 3-year follow-up.

Objective To investigate the predictive effect of multiple serological indicators on the occurrence of heart failure (HF) after percutaneous coronary intervention (PCI) in elderly patients with acute myocardial infarction (AMI). Methods A retrospective study was conducted on 276 elderly AMI patients. Based on whether HF occurred within 6 months, they were divided into HF group (n=65) and non-HF group (n=211). Multivariate Logistic regression was used to screen the influencing factors of AMI complicated with HF. The receiver operating characteristic (ROC) curve was applied to evaluate the efficacy of serological indicators in predicting HF. Results Age, uric acid, fibrinogen, high-sensitivity C-reactive protein (hs-CRP), systemic immune-inflammation index (SII) and level of interleukin-6 (IL-6) in the HF group were significantly higher than those in the non-HF group, while the left ventricular ejection fraction and the proportion of TIMI grade 3 blood flow in the HF group were significantly lower (P < 0.05). Multivariate Logistic regression analysis showed that age (OR=1.401, 95%CI, 1.103 to 1.937), hs-CRP (OR=1.428, 95%CI, 1.108 to 1.839), SII (OR=1.645, 95%CI, 1.262 to 2.145), uric acid (OR=1.376, 95%CI, 1.123 to 1.685) and TIMI grade 3 blood flow (OR=0.502, 95%CI, 0.335 to 0.752) were independent influencing factors for HF after PCI in AMI patients. The ROC curve demonstrated that the area under the curve (AUC) of hs-CRP, SII and uric acid for predicting HF after PCI in AMI patients were 0.694 (95%CI, 0.619 to 0.768), 0.854 (95%CI, 0.796 to 0.912) and 0.716 (95%CI, 0.646 to 0.786), respectively, with sensitivities of 75.38%, 81.54% and 66.15%, and specificities of 57.32%, 74.88% and 73.93%. Conclusion SII has the highest predictive value for HF after PCI in elderly AMI patients, which is helpful for assisting clinical management of high-risk HF populations.

Background/Aims: Binge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs). Methods: Serum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used. Results: A marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated. Conclusions Formation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.

Objective:To analyze clinical manifestations, histopathological and pathogenic fungus characteristics as well as treatment of 3 cases of disseminated cutaneous alternariosis caused by Alternaria. Methods:Clinical data were collected from 3 cases of disseminated cutaneous alternariosis caused by Alternaria, who were diagnosed in Department of Dermatology, Xijing Hospital from 2019 to 2021, and clinical and histopathological features, fungal culture, strain identification and treatment results were retrospectively analyzed. Results:The 3 patients were aged 55, 41 and 46 years respectively, including 1 male and 2 females. Two patients were previously diagnosed with nephrotic syndrome and 1 with systemic lupus erythematosus. All the patients had a history of taking glucocorticoids and tacrolimus for different durations, and experienced chronic infections. Histopathological examination with hematoxylin and eosin (HE) staining showed double-contour thick-walled spores and knot-shaped thick-walled septal hyphae, but no melanin in skin lesions. Sequencing of the fungal internal transcribed spacer region confirmed that 2 cases were infected with Alternaria alternate, and 1 with Alternaria infectoria. Fungal culture at different temperatures showed that the growth ability of Alternaria markedly decreased at the temperature over 35 ℃. To treat these patients, the dose of tacrolimus was reduced to less than 1/3 of the standard dose, or tacrolimus was switched to other immunosuppressants, and systemic antifungal therapy was also given at the same time. After 7-month treatment, good clinical outcomes were achieved in the 3 patients. Conclusion:Disseminated cutaneous alternariosis is characterized by bilateral hematogenous dissemination and lymphatic distribution in unilateral limbs, and the skin lesions are characterized by verrucous plaques covered with scabs, nodules and/or sinuses.

OBJECTIVE: To establish a novel standardized magnetization transfer ratio (MTR) parameter which considers the element of the normal bowel wall and to compare the efficacy of the MTR, normalized MTR, and standardized MTR in evaluating intestinal fibrosis in Crohn's disease (CD).MATERIALS AND METHODS: Abdominal magnetization transfer imaging from 20 consecutive CD patients were analyzed before performing elective operations. MTR parameters were calculated by delineating regions of interest in specified segments on MTR maps. Specimens with pathologically confirmed bowel fibrosis were classified into one of four severity grades. The correlation between MTR parameters and fibrosis score was tested by Spearman's rank correlation. Differences in MTR, normalized MTR, and standardized MTR across diverse histologic fibrosis scores were analyzed using the independent sample t test or the Mann-Whitney U test. The area under the receiver operating characteristic curve (AUC) was computed to test the efficacies of the MTR parameters in differentiating severe intestinal fibrosis from mild-to-moderate fibrosis.RESULTS: Normalized (r = 0.700; p < 0.001) and standardized MTR (r = 0.695; p < 0.001) showed a strong correlation with bowel fibrosis scores, followed by MTR (r = 0.590; p < 0.001). Significant differences in MTR (t = −4.470; p < 0.001), normalized MTR (Z = −5.003; p < 0.001), and standardized MTR (Z = −5.133; p < 0.001) were found between mild-to-moderate and severe bowel fibrosis. Standardized MTR (AUC = 0.895; p < 0.001) had the highest accuracy in differentiating severe bowel fibrosis from mild-to-moderate bowel wall fibrosis, followed by normalized MTR (AUC = 0.885; p < 0.001) and MTR (AUC = 0.798; p < 0.001).CONCLUSION: Standardized MTR is slightly superior to MTR and normalized MTR and therefore may be an optimal parameter for evaluating the severity of intestinal fibrosis in CD.
Crohn Disease ; Fibrosis ; Humans ; Magnetic Resonance Imaging ; ROC Curve

Objective:To explore the diagnostic efficacy of nomogram based on multi-parameter MRI for assessment of bowel fibrosis in patients with Crohn disease（CD).Methods:The clinical and imaging data of CD patients diagnosed by surgical histopathology in the First Affiliated Hospital of Sun Yat-sen University from June 2015 to March 2018 were prospectively collected. All the patients underwent conventional MRI and diffusion kurtosis imaging（DKI) within 2 weeks before surgery. Patients who underwent surgery between June 2015 and September 2017 were included in the model building group, and those who underwent surgery between October 2017 and March 2018 were included in the model validation group. We measured the apparent diffusion coefficient（ADC) from monoexponential model of diffusion-weighted imaging（DWI), apparent diffusional kurtosis（K app), and apparent diffusion for non-Gaussian distribution（D app) from non-Gaussian DKI model, and observed T 2WI signal intensity and enhancement pattern of the same segment. One to three intestinal specimens per patient were stained with Masson′s trichrome for the histological grading of fibrosis. Correlations between qualitative/quantitative MRI indexes and histological grades were evaluated using the Spearman rank test. Multivariate logistic regression analysis was performed to identify independent factors to be included into the nomogram for predicting the degree of bowel fibrosis and its diagnostic performance was assessed by internal and external validation. Results:A total of 40 CD patients were included, including 31 in the model construction group and 9 in the model verification group. A total of 81 intestinal specimens from 31 patients were graded as none-to-mild bowel fibrosis（ n=32) and moderate-to-severe bowel fibrosis（ n=49) according to a scoring system of fibrosis. In the training cohort, the K app value of moderate-to-severely fibrotic bowel walls was significantly higher than that of none-to-mildly fibrotic bowel walls, and the D appand ADC values of moderate-to-severely fibrotic bowel walls were significantly lower than those of none-to-mildly fibrotic bowel walls（ Z=-5.999, -4.521 and -3.893; P<0.001). There was no significant difference in T 2WI signal intensity or enhancement pattern between these two groups（χ2=1.571 and 0.103; P>0.05). Moderate and mild correlations of histological fibrosis grades with K appand D app( r=0.721 and -0.483; P<0.001), and a mild correlation with ADC（ r=-0.445, P<0.001) were found. Independent factors derived from multivariate logistic regression analysis to predict the degree of bowel fibrosis were K app and D app. Internal and external validation revealed good performance of the nomogram with concordance index of 0.901（95% confidence interval, 0.824-0.978) and 1.000, respectively, for differentiating none-to-mild from moderate-to-severe fibrosis. Conclusion:The DKI-based nomogram can be used to evaluate the bowel fibrosis in CD patients and provides a visual and simple prediction method for clinic.

Objective To determine the correlation between intravoxel incoherent motion (IVIM) parameters and both histologic inflammatory and fibrotic grades of Crohn disease (CD) in adults. Methods Prospectively, 17 patients (77 lesions) with a clinical and pathological diagnosis of CD in the first affiliated hospital of sun yat-sen university from July 2015 to June 2016 underwent MRE 15 days before surgery. All patients underwent T2WI, IVIM and enhanced MRI and calculated IVIM parameters include diffusion-related coefficient (D), perfusion-related coefficient (D*) and perfusion-related fraction (f). Histological intestinal inflammation and fibrosis was scored using the surgical histopathology as reference standard and further divided into mild-moderate (score 1 to 2) and severe (score 3 to 4) groups. Intestinal microvessel density (MVD) were also analyzed. Differences in IVIM parameters among different histological inflammation and fibrosis grades were assessed with the Kruskal-Wallis test. The Wilcoxon test was used for assessing differences in f between mild-moderate and severe fibrosis. The bivariate correlations between IVIM parameters and histological inflammation and fibrosis grades were analyzed using partial correlation . The bivariate correlations between IVIM parameters and MVD were analyzed using Spearman rank correlation. The areas under the receiver operating characteristics curves (AUROC) were analyzed to evaluate the efficacy for distinguishing severe from mild-moderate fibrosis. Results Of 77 surgical specimens, there were 41 mild-moderate and 36 severe inflammatory bowel segments, along with 22 mild-moderate and 55 severe fibrotic bowel segments. Positive correlation was shown between histologic inflammatory and fibrotic scores (r=0.592, P<0.01). MVD (42.7 ± 39.9)/HP presented weak positive correlation with histologic inflammatory scores (r=0.332, P=0.003) while no correlation with histologic fibrotic scores (r=0.129, P=0.262) was presented. Neither the D nor the D* values significantly correlated with histologic inflammation or fibrosis (P>0.05) while the f value significantly correlated with both histologic inflammation and fibrosis (P<0.05). Significant correlation was present between the f value and histologic inflammatory and fibrotic scores, respectively (r=-0.280, -0.520;P<0.05). There was significant difference in the f value between mild-moderate and severe fibrosis(Z=-5.255,P<0.01). The AUROC for the f value to distinguish between patients with mild-moderate fibrosis and severe fibrosis were 0.885. Using a threshold fractional perfusion of 0.33, the sensitivity and specificity values were 95.5％ and 81.8％, respectively. No correlation between f, D and D*value with histologic fibrotic scores (r=0.129, P=0.262) was presented. Conclusion The f value derived from IVIM could help to evaluate the severity of intestinal inflammation and fibrosis CD in adults.