Aldehyde dehydrogenase 2 (ALDH2) is one of important factors against from the damage under oxidative stress in human body. A high proportion of East Asians carry ALDH2 inactive mutation gene. There are many diseases closely related to ALDH2, such as cardiovascular diseases, neurodegenerative diseases and liver diseases. Recent studies also have found that ALDH2 is associated with ferroptosis. Therefore, ALDH2 has becoming a potential target for the treatment of the above related diseases. Several types of small molecule activators with potential value of clinical application have been reported. The research progress on the structure and function of ALDH2 , the relationship with human diseases and its activators were summarized in this paper.

Objective:To explore the clinical features and genetic etiology of a Chinese pedigree affected with Cowden syndrome (CS).Methods:A CS pedigree diagnosed in November 2022 at the Ningde Municipal Hospital Affiliated to Ningde Normal University was selected as the study subject. Clinical data were collected, and genetic testing was carried out for available members. Pathogenicity analysis was carried out for the candidate variant.Results:The proband, a 7-year-old male, was found to have autism and intellectual disability. Whole exome sequencing revealed that he has harbored a c. 462_463del (p.F154Lfs25) variant of the PTEN gene. The proband′s 35-year-old mother, who was diagnosed with pulmonary hamartomas at our hospital, has manifested with lipomas, nodular goiter, and adenomas. Sanger sequencing confirmed that she was also heterozygous for the c. 462_463del (p.F154Lfs25) variant of the PTEN gene. No other family members has carried the same variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PM6). Conclusion:The newly discovered c. 462_463del (p.F154Lfs*25) variant of the PTEN gene probably underlay the CS in this pedigree. CS patients have higher risk for developing malignant tumors. Clinicians should be aware of this condition and emphasize follow-up of the patients.

Objective:To investigate the factors affecting the application of systemic glucocorticoids in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with carbon dioxide (CO 2) retention, and to guide the formulation of a strategy to reduce systemic glucocorticoid exposure. Methods:The AECOPD patients with CO 2 retention admitted to the Ningde Municipal Hospital of Fujian Medical University from January 2017 to December 2019 were enrolled. The general information, past history, times of acute exacerbations within 1 year, pneumonia on admission, causes of COPD, heart failure, blood gas analysis, eosinophil count (EOS), albumin (Alb) and apolipoprotein E (ApoE) levels, exhaled nitric oxide (FeNO) level, inhaled glucocorticoid and non-invasive mechanical ventilation treatment at acute exacerbation were collected. The patients were divided into recommended dosage group (exposure levels in the recommended dosage range, cumulative prednisone dosage ≤ 200 mg) and exceeded group (exposure levels exceeded the recommended dose, cumulative prednisone dosage > 200 mg) according to cumulative systemic glucocorticoid exposure dosage of the patients during hospitalization. The clinical data of patients between the two groups were compared, and possible factors with P < 0.1 in univariate analysis were included in multivariate Logistic regression analysis to screen the related factors of systemic glucocorticoid exposure level in AECOPD patients with CO 2 retention. Results:According to the order of hospitalization, 151 AECOPD patients with CO 2 retention were enrolled, 8 patients were excluded, and 143 patients were enrolled in the analysis. Of the 143 patients, 68 received the recommended dose of systemic glucocorticoid, and 75 received excessive systemic glucocorticoid. Age, percentage of forced expiratory volume in 1 second (FEV1%) at stable phase, frequency of acute exacerbation within 1 year, heart failure ratio, oxygen index (PaO 2/FiO 2), arterial partial pressure of carbon dioxide (PaCO 2), serum EOS and ApoE levels at admission, the ratio of aerosolized inhaled glucocorticoids and non-invasive mechanical ventilation showed statistical differences between the two groups. Multivariate Logistic regression analysis showed that related factors affecting systemic glucocorticoid exposure levels of AECOPD patients with CO 2 retention were FEV1% at stable phase [odds ratio ( OR) = 0.957, 95% confidence interval (95% CI) was 0.921-0.994, P = 0.023], acute exacerbation frequency within 1 year ( OR = 1.530, 95% CI was 1.121-2.088, P = 0.007), heart failure ( OR = 3.022, 95% CI was 1.263-7.231, P = 0.013), PaCO 2 ( OR = 1.062, 95% CI was 1.010-1.115, P = 0.018) and EOS at admission ( OR = 0.103, 95% CI was 0.016-0.684, P = 0.019), aerosolized inhaled glucocorticoids ( OR = 0.337, 95% CI was 0.145-0.783, P = 0.011) and non-invasive mechanical ventilation at acute exacerbation ( OR = 0.422, 95% CI was 0.188-0.948, P = 0.037), of which high FEV1% at stable phase, high EOS at admission, aerosolized inhaled glucocorticoid and non-invasive mechanical ventilation at acute exacerbation were protective factors, while high frequency of acute exacerbation within 1 year, heart failure and high PaCO 2 were risk factors. Conclusions:For AECOPD patients with CO 2 retention, high FEV1% at stable phase, high EOS level at admission, aerosolized inhaled glucocorticoid and non-invasive mechanical ventilation at acute exacerbation can reduce systemic glucocorticoid exposure. In addition, high frequency of acute exacerbation within 1 year, heart failure, and high PaCO 2 can increase systemic glucocorticoid exposure.

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 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.

Objective To assess the diagnostic value of magnetization transfer MRI (MTI) for bowel inflammation and fibrosis in humans with Crohn disease (CD). Methods From July 2014 through April 2017, 31 patients with a confirmed diagnosis of CD were prospectively recruited from the First Affiliated Hospital of Sun Yat Sen University. They were scheduled for elective surgery due to bowel obstruction and other complications, and underwent preoperative MR enterography (MRE) and MTI within 15 days of surgery. All cases had available intestinal specimens identified on MRE and resected bowel segments for region by region matching. All patients underwent breath hold conventional MRE and MTI examinations, and then the magnetization transfer ratios (MTRs) of pathological bowel segments were measured. Using region by region correlation between MTI and surgical specimen, the bowel segments were resected to stain with HE for evaluating bowel inflammation, Masson for bowel fibrosis, and typeⅠcollagen staining for the deposition of typeⅠcollagen within the bowel walls. The histologic sections from the most severe areas were scored as 0 (normal), 1 (mild), 2 (moderate) and 3 (severe). The correlations between MTR and histologic scores were analyzed by using Spearman rank correlation or partial correlation. The differences in MTR among different grades of bowel fibrosis were analyzed by one way ANOVA. The efficacy of MTR for predicting bowel fibrosis was evaluated by receiver operating characteristic curves analysis. The difference in MTRs between purely inflammatory bowel walls and mixed fibrotic and inflammatory bowel walls was analyzed by Student s t test. Results Sixty two resected bowel specimens from 31 patients including 9 purely inflammatory bowel walls and 53 mixed fibrotic and inflammatory bowel walls were obtained in this study. There were significant differences in MTR among non fibrotic [(21.45 ± 2.65)%], mildly [(30.88 ± 6.14)%], moderately [(35.14 ± 4.31)%] and severely [(35.14 ± 4.31)%] fibrotic walls (F=38.397,P<0.01). MTRs strongly correlated with fibrosis scores (r=0.681, P<0.01). High accuracy of MTRs was shown (curve under area=0.905, P<0.01) for differentiating moderately severely fibrotic from non fibrotic and mildly fibrotic bowel walls. Using MTR of 31.50% as a cutoff value, the sensitivity and specificity were 93.6% and 80.0%, respectively. The MTRs of purely inflammatory bowel walls [(21.45 ± 2.65)%] were significantly higher than that of mixed fibrotic and inflammatory [(36.28±5.21)%] bowel walls (t=-13.052,P<0.01). MTRs correlated with the scores of type Ⅰ collagen (r=0.325, P=0.044) but did not correlate with inflammation scores (r=-0.024, P=0.857). Conclusions MTI enables quantitative evaluation of bowel fibrosis in patients with CD and can be used to differentiate purely inflammatory CD from mixed fibrotic and inflammatory CD.

Objective To analyze the relationship between pillow height and cervical intervertebral disc stress in lateral decubitus position of the human body using three-dimensional finite element method,and to provide the basis for appropriate pillow selection.Methods A cervical spine CT scan was performed on a normal male volunteer.The medical 3D image reconstruction software (Mimics),reverse engineering software (Geomagic Studio) and finite element software (MSC.Patran) were collectively used to establish three-dimensional finite element models of the whole cervical spine under three lateral decubitus conditions,includes pillow height of 10 cm (cervical spine leftward flexion),17 cm (cervical spine neutral),and 25 cm (cervical spine rightward flexion).Moreover,the finite element analysis and calculation of the three models were conducted.Results The Von-Mises stress,maximal principal stress and maximum shear stress of the model in cervical spine neutral (pillow height=17 cm) were all significantly lower than those of the cervical spine lateral model.Conclusions When the cervical coronal plane is in neutral position,the cervical discs can achieve the best stress distribution state.In lateral decubitus position of the human body,a appropriate pillow height should make the cervical vertebrae in neutral position.

BACKGROUND: Microglia play an important role in immune surveillance in their quiescent state, but the role of the activated microglia is under discussion. OBJECTIVE: To analyze the mechanism of activated microglia in acute cerebral infarction. METHODS: Totally 96 male Kunming mice were selected and randomly divided into four groups, including transplantation, placebo, blank control and sham operation groups. Permanent occlusion of the middle cerebral artery was performed using suture method in the mice of the transplantation, placebo and blank control groups, followed by injection of microglia suspension via subclavian vein, medium containing the same volume of microglia, and nothing, respectively, at 12 hours after modeling. In the meanwhile, the same amount of microglia suspension was injected into the mice of the sham operation group. The Zea-longa scale and brain-derived neurotrophic factor expression at 12, 24 and 72 hours after modeling, the volume of cerebral infarction and the number of nerve cells positive for microtubule-associated protein-2 at 72 hours after modeling were detected. RESULTS AND CONCLUSION: The Zea-longa scale score was 0 point in the sham operation group, which was significantly lower than that in the other three groups at each time point after modeling (P < 0.01). The Zea-longa scores in the transplantation group were significantly lower than those in the placebo and blank control groups at 24 and 72 hours after transplantation (P < 0.01). The positive expression rate of brain-derived neurotrophic factor in the transplantation group was significantly higher than that in the other three groups after transplantation (P < 0.01). The sham group showed no infarction, while the size of cerebral infarction in the transplantation group was significantly lower than that in the placebo and blank control groups (P < 0.01), and the microtubule-associated protein-2 positive rate was significantly higher than that in the placebo and blank control groups (P < 0.01). These results manifest that the activated microglia can improve the survival rate of nerve cells, promote the recovery of cerebral nerve function and reduce the size of cerebral infarction.

Objective To investigate the protective effect of sevoflurane on acute intracranial hemorrhage craniotomy patients. Methods 60 acute intracranial hemorrhage craniotomy surgery patients were randomly divid?ed into control and experimental group of 30 patients under general anesthesia to have craniotomy. The patients in control group was operated by propofol and remifentanil as a inhalation anesthesia ,while patients in experimental group received sevoflurane ,propofol and remifentanil as a mixed anesthesia. Then intracranial pressure ,serum C?reactive protein(CRP),serum S?100β,NSE,IL?6 and TNF?α levels of different time points were deternmined. Results Serum CRP in experimental group were significantly decreased than the control group(P<0.05)1 d af?ter operation. T0~T3 levels of serum S?100β,NSE,IL?6 and TNF?α in two groups were both increased(P <0.05),and the experimental group was significantly lower than the control group(P < 0.05). The intracranial pressure of control group was significantly higher than the experimental group(P < 0.05). Conclusion Sevoflu?rane has a brain protective role in inhibiting acute inflammation in intracranial hemorrhage craniotomy patients.