1.Neuronal intranuclear inclusion disease: the clinical features and pathological findings of peripheral tissue biopsy in nine cases with genetic diagnosis
Muliang GU ; Jianwen DENG ; Jiaxi YU ; Jing BAI ; Fan LI ; Wei SUN ; Hong ZHOU ; Qun HU ; Zhirong WAN ; Yining HUANG ; Yun YUAN ; Zhaoxia WANG
Chinese Journal of Neurology 2021;54(3):219-227
Objective:To summarize the clinical features and pathological changes of peripheral tissues from patients with neuronal intranuclear inclusion disease (NIID) diagnosed by genetic tests.Methods:Repeat-primed polymerase chain reaction was used to confirm the GGC repeated expansion in the 5′ untranslated region of the NOTCH2NLC gene in patients with suspected NIID who had visited the Department of Neurology of Peking University First Hospital from January 2018 to February 2020. The clinical data and pathological changes of peripheral tissues from patients with genetically diagnosed NIID were collected retrospectively and analysed. Immunostaining with anti-p62 and anti-ubiquitin antibody was performed on peripheral biopsy specimens.Results:Totally nine patients with NIID who had GGC repeated expansion in the NOTCH2NLC gene were found. Five patients were familial (from three faimilies), and four patients were sporadic. The age of onset was 36-61(51.33±7.12) years. The most common symptoms in this NIID group were episodic emotion and personality change (8/9), paroxysmal disturbance of consciousness (6/9) and intermitant head discomfort (6/9). Other symptoms included cognitive dysfunction, limb weakness, limb sensory disturbance, bladder dysfunction, ataxia, seizures and psychiatric symptoms. Brain magnetic resonance imaging showed high signals along the corticomedullary junction on diffusion-weighted image in eight out of nine patients. Skin biopsied samples from nine patients demonstrated the presence of eosinophilic intranuclear inclusions (IIs), appearing in the nucleus of fibroblasts, fat cells and ductal epithelial cells of sweat glands on hematoxylin-eosin staining. IIs were positive on anti-p62 and anti-ubiquitin immunostaining. Electron microscopy indicated the IIs were composed of a pile of filament materials without membrane. Muscle biopsies from two patients showed no obvious neurogenic or myogenic pathologic changes, except in one patient several rimmed vacuoles fibers were found. In one patient sural nerve biopsy showed severe demyelinating pathological changes. No IIs were found in the muscles and peripheral nerve tissue either by histological examination or by immunohistochemical staining with anti-p62 or anti-ubiquitin, while IIs were found by immunofluorescence staining with both anti-p62 and anti-ubiquitin in three patient′s tissue. Conclusions:The phenotype of this NIID patient group is adult-onset NIID, with episodic encephalopathy as the main clinical manifestation. Skin biopsy has high pathological diagnostic value for NIID. The immunofluorescence staining with anti-p62 and anti-ubiquitin is easier to detect the presence of IIs than histological staining and immumohistochemical staining.
2.Risk factors of spinal cord injury after total aortic arch replacement and frozen elephant trunk
Zhiqiang DONG ; Jie JIANG ; Hong LIU ; Jiaxi GU ; Minghui LI ; Buqing NI
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(10):590-595
Objective:To investigate the risk factors of spinal cord injury after FET for ATAAD.Methods:We analyzed perioperative data of 111 patients with ATAAD who underwent FET in the First Affiliated Hospital of Nanjing Medical University from January 2020 to October 2021.Results:Eleven(9.9%)of 111 patients had postoperative spinal cord injury, which showed varying degrees of paralysis or paraplegia. There was no significant difference in age, sex, medical history, cardiopulmonary bypass time, aortic cross-clamping time, circulatory arrest time and FET length between spinal cord injury group and non-spinal cord injury group( P>0.05). Univariate analysis showed that aortic true lumen away from the spinal side( P<0.001) and the number of segmental arteries originating from the true lumen<3 in T9-L3( P<0.001), left subclavian artery involvement( P<0.05) and stent coverage at T8 or beyond( P<0.05) was associated with postoperative spinal cord injury. Multivariate Logistic analysis showed that aortic true lumen away from the spinal side( P<0.001) and the number of segmental arteries originating from the true lumen<3( P<0.001) in T9-L3 and left subclavian artery involvement( P<0.05) were independent risk factors for postoperative spinal cord injury. Conclusion:The pathogenesis of spinal cord injury is complicated. This study suggests that the occurrence of spinal cord injury is significantly related to aortic true lumen away from the spinal side and the number of segmental arteries originating from the true lumen<3 in T9-L3 and left subclavian artery involvement. It is of great clinical significance to identify the high risk factors of postoperative spinal cord injury as early as possible.
3.Effect of Sanhuang Tangshenkang on Wnt/β-catenin Signaling Pathway in Bone Tissue of Diabetic Rats
Liya SUN ; Liyan GU ; Bei LIU ; Jiaxi WANG ; Yinan FENG ; Yue XI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(18):69-77
ObjectiveTo observe the effect of Sanhuang Tangshenkang on the Wnt/β-catenin signaling pathway in the bone tissue of diabetic rats. MethodA high-sugar and high-fat diet was administered for 4 weeks, along with intraperitoneal injection of freshly prepared 2% streptozotocin (pH 4.5) at 30 mg·kg-1 body weight to induce a diabetes model in rats. The rats with diabetes were randomly divided into model group, low- and high-dose Sanhuang Tangshenkang groups (12.8, 38.4 g·kg-1), and Gushukang group (1.8 g·kg-1) according to the blood glucose level. Rats of the same age were fed on a regular diet and assigned to the control group. After 12 weeks of respective treatments with drugs or physiological saline, the fasting blood glucose (FBG) levels of the rats were measured using an automated biochemical analyzer. Enzyme-linked immunosorbent assay (ELISA) was used to detect fasting serum insulin (FINS), bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase (TRAP) levels. Micro-computed tomography (Micro-CT) was used to scan the femurs of rats to observe bone tissue microstructure and measure bone mineral density (BMD). Hematoxylin-eosin (HE) staining and safranin O/fast green staining were performed to observe pathological changes in the femoral bone tissue. Immunohistochemistry (IHC) and Western blot were used to detect the expression of Wnt3a, low-density lipoprotein receptor-related protein 5 (LRP-5), and β-catenin proteins. ResultCompared with the control group, the model group showed a significant increase in FBG, FINS, and TRAP levels (P<0.01), a significant decrease in BALP level (P<0.01), a significant decrease in BMD (P<0.01), and disorganized, elongated, and sparse bone trabecular structures with fractures and increased lipid droplets. Additionally, the expression of Wnt3a, LRP-5, and β-catenin proteins decreased (P<0.05, P<0.01). Compared with the model group, the low- and high-dose Sanhuang Tangshenkang groups showed a reduction in FBG and an increase in BALP (P<0.05). The low-dose Sanhuang Tangshenkang group also exhibited a decrease in FINS (P<0.05). All treatment groups showed a significant decrease in TRAP (P<0.01), varying degrees of improvement in BMD (P<0.05, P<0.01)), increased and denser bone trabeculae with more regular arrangements and reduced lipid droplets, and improved bone microstructure morphology. The average optical density values of Wnt3a, LRP-5, and β-catenin proteins were significantly increased in all drug-treated groups (P<0.05, P<0.01), and the expression of Wnt3a, LRP-5, and β-catenin proteins was elevated (P<0.05, P<0.01). ConclusionSanhuang Tangshenkang may regulate the imbalance of the Wnt/β-catenin signaling pathway by increasing the expression of Wnt3a, LRP-5, and β-catenin proteins in bone tissue, which may promote bone formation, reduce bone resorption, and lower blood glucose levels, thereby achieving the effect of preventing and treating diabetic osteoporosis.
4.Application of machine learning model based on XGBoost algorithm in early prediction of patients with acute severe pancreatitis.
Xin GAO ; Jiaxi LIN ; Airong WU ; Huiyuan GU ; Xiaolin LIU ; Minyue YIN ; Zhirun ZHOU ; Rufa ZHANG ; Chunfang XU ; Jinzhou ZHU
Chinese Critical Care Medicine 2023;35(4):421-426
OBJECTIVE:
To establish a machine learning model based on extreme gradient boosting (XGBoost) algorithm for early prediction of severe acute pancreatitis (SAP), and explore its predictive efficiency.
METHODS:
A retrospective cohort study was conducted. The patients with acute pancreatitis (AP) who admitted to the First Affiliated Hospital of Soochow University, the Second Affiliated Hospital of Soochow University and Changshu Hospital Affiliated to Soochow University from January 1, 2020 to December 31, 2021 were enrolled. Demography information, etiology, past history, and clinical indicators and imaging data within 48 hours of admission were collected according to the medical record system and image system, and the modified CT severity index (MCTSI), Ranson score, bedside index for severity in acute pancreatitis (BISAP) and acute pancreatitis risk score (SABP) were calculated. The data sets of the First Affiliated Hospital of Soochow University and Changshu Hospital Affiliated to Soochow University were randomly divided into training set and validation set according to 8 : 2. Based on XGBoost algorithm, the SAP prediction model was constructed on the basis of hyperparameter adjustment by 5-fold cross validation and loss function. The data set of the Second Affiliated Hospital of Soochow University was served as independent test set. The predictive efficacy of the XGBoost model was evaluated by drawing the receiver operator characteristic curve (ROC curve), and compared it with the traditional AP related severity score; variable importance ranking diagram and Shapley additive explanation (SHAP) diagram were drawn to visually explain the model.
RESULTS:
A total of 1 183 AP patients were enrolled finally, of which 129 (10.9%) developed SAP. Among the patients from the First Affiliated Hospital of Soochow University and Changshu Hospital Affiliated to Soochow University, there were 786 patients in the training set and 197 in the validation set; 200 patients from the Second Affiliated Hospital of Soochow University were used as the test set. Analysis of all three datasets showed that patients who advanced to SAP exhibited pathological manifestation such as abnormal respiratory function, coagulation function, liver and kidney function, and lipid metabolism. Based on the XGBoost algorithm, an SAP prediction model was constructed, and ROC curve analysis showed that the accuracy for prediction of SAP reached 0.830, the area under the ROC curve (AUC) was 0.927, which was significantly improved compared with the traditional scoring systems including MCTSI, Ranson, BISAP and SABP, the accuracy was 0.610, 0.690, 0.763, 0.625, and the AUC was 0.689, 0.631, 0.875, and 0.770, respectively. The feature importance analysis based on the XGBoost model showed that the top ten items ranked by the importance of model features were admission pleural effusion (0.119), albumin (Alb, 0.049), triglycerides (TG, 0.036), Ca2+ (0.034), prothrombin time (PT, 0.031), systemic inflammatory response syndrome (SIRS, 0.031), C-reactive protein (CRP, 0.031), platelet count (PLT, 0.030), lactate dehydrogenase (LDH, 0.029), and alkaline phosphatase (ALP, 0.028). The above indicators were of great significance for the XGBoost model to predict SAP. The SHAP contribution analysis based on the XGBoost model showed that the risk of SAP increased significantly when patients had pleural effusion and decreased Alb.
CONCLUSIONS
A SAP prediction scoring system was established based on the machine automatic learning XGBoost algorithm, which can predict the SAP risk of patients within 48 hours of admission with good accuracy.
Humans
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Pancreatitis
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Acute Disease
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Retrospective Studies
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Hospitalization
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Algorithms