This paper analyzed the "non-standardization" phenomenon of syndrome differentiation in traditional Chinese medicine （TCM） from the diagnosis process. It is proposed that the symptoms and signs collected by the four examinations of inspection， listening/smelling， inquiry， and palpation naturally have a certain "ambiguity"， which can be reduced by the comparison and comprehensive condensation （comprehensive analysis of the four examinations） of a large amount of multi-dimensional clinical data， thereby realizing the sublimation of TCM diagnosis from "ambiguity" of four examinations to "accuracy" of diagnostic conclusion. Based on the above assumptions， this paper further proposed that a research idea of intelligent syndrome differentiation in TCM， that is， by taking the clinical thinking ability of TCM physicians as the core， adopting artificial intelligence technology based on knowledge graph visualization， integrating the complex network association and reasoning method of "symptom-pathogenesis-syndrome" linked by pathogenesis， and through the automatic analysis and reasoning process of a large amount of multi-dimensional and ambiguous clinical data， the intelligent TCM diagnosis based on syndrome differentiation can be realized.

Objective:To investigate the clinical and cardiac magnetic resonance (CMR) characteristics of heart involvement in patients with Fabry disease (AFD).Methods:From January 2018 to March 2021, eight AFD patients [3 males and 5 females, mean age (50±11) years old, range 26-60 years old] confirmed by genetic testing or pathology in Fuwai Hospital were retrospectively included in this study. At the same time, sixteen patients with hypertrophic cardiomyopathy (HCM) [6 males and 10 females, mean age (46±15) years old] and 16 healthy individuals [6 males and 10 females, mean age (51±11) years old] were included as controls. The clinical baseline data and CMR data of the patients were collected and analyzed. The CMR data were analyzed using the software CVI42, with the corresponding parameters automatically generated. One-way ANOVA or Kruskal-Wallis test was used to compare the differences in the parameters among the three groups. Independent-samples t test, Fisher precise test or Mann-Whitney U test were used for the comparison between each two groups. Results:Statistically significant difference was found in renal insufficiency between the HCM group and the AFD group; No other significant difference was found in other clinical factors and ECG results (all P>0.05). CMR results showed that in the AFD group, there were 5 cases with symmetric or roughly symmetric hypertrophy, and 3 with asymmetric hypertrophy. The late gadolinium enhancement (LGE) showed myocardial enhancement in 5 patients, mainly presenting as multiple intermural enhancement, and partially as local subendocardial enhancement. In the HCM group, fourteen cases suffered mainly asymmetric ventricular septal thickening, with or without thickening of other parts of left ventricular wall; and 2 cases had thickening of middle and distal part of the left ventricle. The LGE showed myocardial enhancement in 14 patients, which manifested as focal or patchy enhancement in hypertrophic myocardium, including focal enhancement in the right ventricular insertion of ventricular septum (more common) and subendocardial enhancement in the middle and far segments of left ventricle. Statistically significant difference was found in the differences between the left atrial anterior posterior diameter, the maximum wall thickness of left ventricular, the left ventricular myocardial mass index (LVMI) and the native T 1 value among the three groups (all P<0.001). However, there was no statistically significant difference in the left atrial anterior posterior diameter and the maximum wall thickness of left ventricular between AFD group and HCM group ( P>0.05). The LVMI in AFD group was higher than that in healthy group and HCM group (all P<0.05). Significant difference was found in the native T 1 value among the three groups, with the native T 1 value of the AFD group [(1 177.4±46.0) ms] was significantly lower than that of the healthy group [(1 244.5±34.3) ms] and the HCM group [(1 278.8±41.6) ms], with ( F=13.10, P<0.001). Conclusions:The clinical characteristics of AFD and HCM are quite similar. When AFD is suspected, CMR imaging should be the first choice for imaging examination. Especially, T 1 mapping imaging can provide important information for the diagnosis of AFD.

Mammalian bone is constantly metabolized from the embryonic stage, and the maintenance of bone health depends on the dynamic balance between bone resorption and bone formation, mediated by osteoclasts and osteoblasts. It is widely recognized that circadian clock genes can regulate bone metabolism. In recent years, the regulation of bone metabolism by non-coding RNAs has become a hotspot of research. MicroRNAs can participate in bone catabolism and anabolism by targeting key factors related to bone metabolism, including circadian clock genes. However, research in this field has been conducted only in recent years and the mechanisms involved are not yet well established. Recent studies have focused on how to target circadian clock genes to treat some diseases, such as autoimmune diseases, but few have focused on the co-regulation of circadian clock genes and microRNAs in bone metabolic diseases. Therefore, in this paper we review the progress of research on the co-regulation of bone metabolism by circadian clock genes and microRNAs, aiming to provide new ideas for the prevention and treatment of bone metabolic diseases such as osteoporosis.
Animals ; Circadian Clocks/genetics* ; Circadian Rhythm/genetics* ; Mammals/genetics* ; MicroRNAs/genetics* ; Osteogenesis/genetics* ; Osteoporosis/genetics*

Objective:To investigate the characteristics and change trends of electroencephalogram (EEG) in patients with drug resistant epilepsy (DRE) after vagus nerve stimulation (VNS).Methods:Twenty-five patients with DRE, admitted to our hospital from July 2016 to May 2019, were chosen; all patients accepted VNS and followed up for 12 months. Long range video EEG (VEEG) monitoring was performed before VNS, and 3, 6 and 12 months after VNS, and the tracing time of each monitoring was longer than 12 h. The EEG characteristics of these patients before and different times after VNS were analyzed.Results:In the VEEG monitoring before VNS, 25 patients showed sharp wave, spike wave, sharp slow wave, and compound spike slow wave in the interictal period; 3 patients (12%) could locate the brain region. The interictal EEG of 11 patients 3 months after VNS showed different degrees of improvement as compared with the preoperative one, which manifested as mixed rhythms: mono-spiking as sharp wave, sharp slow wave or spike wave; 8 patients had McHugh grading I-II. The interictal EEG of 18 patients 6 months after VNS showed different degrees of improvement as compared with the preoperative one; 11 patients had McHugh grading I-II. The interictal EEG of 21 patients 12 months after VNS showed different degrees of improvement as compared with the preoperative one; 15 patients had McHugh grading I-II.Conclusion:The EEG improvement effect of DRE patients after VNS is gradually improved with time; in some patients, the EEG improvement is earlier than improvement of clinical symptoms.

Objective:To investigate the characteristics and change trends of electroencephalogram (EEG) in patients with drug resistant epilepsy (DRE) after vagus nerve stimulation (VNS).Methods:Twenty-five patients with DRE, admitted to our hospital from July 2016 to May 2019, were chosen; all patients accepted VNS and followed up for 12 months. Long range video EEG (VEEG) monitoring was performed before VNS, and 3, 6 and 12 months after VNS, and the tracing time of each monitoring was longer than 12 h. The EEG characteristics of these patients before and different times after VNS were analyzed.Results:In the VEEG monitoring before VNS, 25 patients showed sharp wave, spike wave, sharp slow wave, and compound spike slow wave in the interictal period; 3 patients (12%) could locate the brain region. The interictal EEG of 11 patients 3 months after VNS showed different degrees of improvement as compared with the preoperative one, which manifested as mixed rhythms: mono-spiking as sharp wave, sharp slow wave or spike wave; 8 patients had McHugh grading I-II. The interictal EEG of 18 patients 6 months after VNS showed different degrees of improvement as compared with the preoperative one; 11 patients had McHugh grading I-II. The interictal EEG of 21 patients 12 months after VNS showed different degrees of improvement as compared with the preoperative one; 15 patients had McHugh grading I-II.Conclusion:The EEG improvement effect of DRE patients after VNS is gradually improved with time; in some patients, the EEG improvement is earlier than improvement of clinical symptoms.

Objective:To investigate the changes of strains based on feature tracking in patients with hypertrophic obstructive cardiomyopathy (HOCM) after surgical myectomy and the potential factors that influenced post-myectomy global strains.Methods:A total of 27 patients with HOCM who underwent septal myectomy in Fuwai Hospital from June 2014 to July 2017 were retrospectively collected. They all received cardiac MR (CMR) cine acquisitions before and after surgery. Their preoperative and postoperative strain parameters, including radial strain (RS), circumferential strain (CS), and longitudinal strain (LS) of the global left ventricle, septum, and lateral wall, were assessed by feature tracking. Comparisons of pre-myectomy and post-myectomy imaging parameters were performed using paired-samples t-test or Wilcoxon matched-pairs signed-ranks test. Pearson or Spearman correlation analysis and linear regression analysis were utilized to find the correlated factors of postoperative global strains. Results:Compared with preoperative strains, postoperative global LS, septal LS, lateral RS, lateral CS, and lateral LS increased statistically (all P<0.05); postoperative global RS, global CS, and septal CS decreased (all P<0.05); no statistically significant difference was observed in septal RS ( P=0.165). Age at surgery ( r=0.428, P=0.026) and preoperative myocardial maximum ventricular wall thickness ( r=-0.587, P=0.001) were both linearly related to postoperative global RS; the further multivariate stepwise linear regressions showed that only preoperative myocardial maximum ventricular wall thickness might be correlated with postoperative global RS (adjusted R 2=0.287, P=0.002). Only myocardial maximum ventricular wall thickness was linearly related to global CS ( r=0.679, P<0.001) and global LS ( r=0.588, P=0.001), respectively; univariate linear regression revealed that preoperative myocardial maximum ventricular wall thickness might be correlated postoperative global CS (adjusted R 2=0.337, P=0.001) and postoperative global LS (adjusted R 2=0.281, P=0.003), respectively. Conclusions:Cardiac surgery definitely relieves left ventricular outflow tract obstruction and generally improves longitudinal and lateral strains, but a negative impact may occur in global and septal CS and RS. Preoperative maximum ventricular wall thickness may affect postoperative global strains.

Objective:To explore the role of transgelin(TAGLN) in the occurrence and development of papillary thyroid carcinoma (PTC) and its possible signal pathway.Methods:One hundred cases of PTC tissues and corresponding paracancerous normal thyroid tissues were collected. Realtime quantitative PCR (RT-qPCR), Western blotting, and immunohistochemistry were used to analyze the expression of TAGLN in PTC tissues and corresponding paracancerous normal thyroid tissues. PTC cells were transfected with plasmid and shRNA lentivirus vector respectively to up-regulate or down-regulate the expression of TAGLN in order to detect the effects of them on the proliferation, invasion, and migration by cell proliferation assay(cell counting kit-8, CCK-8)and cell invasion and migration assays (Transwell). The effects of TAGLN on mitogen-activated protein kinase (MAPK)/extracellular-signal regulating kinase (ERK) signal pathway was detected with Western blotting.Results:RT-qPCR showed that there was no difference in the expression of TAGLN mRNA between PTC and corresponding paracancerous normal thyroid tissues ( P>0.05); Western blotting demonstrated that the expression of TAGLN protein in PTC tissues was significantly lower than that in corresponding paracancerous normal thyroid tissues ( P<0.01). Immunohistochemical results revealed that the expression of TAGLN in PTC tissues was significantly lower than that in corresponding paracancerous normal thyroid tissues. Overexpression of TAGLN inhibited the proliferation, invasion, and migration of PTC cells ( P<0.01), but knockdown of TAGLN promoted the proliferation, invasion, and migration of PTC cells ( P<0.01). Overexpression of TAGLN decreased the expression of phosphorylated ERK ( P<0.05), whereas silencing TAGLN increased phosphorylated ERK level in PTC cells( P<0.01). Conclusion:The expression of TAGLN in PTC is significantly decreased. It is related to the occurrence and development of PTC, and its mechanism may be related to MAPK/ERK signal pathway.

Objective: To investigate the feasibility and consistency of four-dimensional flow (4D flow) quantification of pulmonary regurgitation in patients with repaired Tetralogy of Fallot (ToF) by comparing with conventional two-dimensional flow (2D flow) and echocardiography. Methods: Both the 4D flow and 2D flow imaging were acquired with repaired ToF (a total of 21 patients) consecutively on 3.0 T MR scanner from May 2018 to August 2018. Pulmonary flow and regurgitant fraction were measured by a commercial post processing software Circle CVI42. All patients underwent echocardiography within one week after or before MR examination. The inter/intra-observer variability by 2D/4D f1ow and agreement between the two methods were investigated by interclass correlation coefficients (ICC) and Bland-Altman analyses. The agreement between MR and echocardiography were analyzed by weighted Kappa coefficient. The correlation between pulmonary regurgitation and cardiac function was also investigated by Pearson analysis. Results: All patients were included and completed the examinations successfully. Both inter-observer and intra-observer agreement by 4D flow for total forward volume (ICC=0.993, 0.996, respectively, P<0.001), total backward volume (ICC=0.994, 0.997, respectively, P<0.001) and regurgitant fraction (ICC=0.968, 0.985, respectively, P<0.001) were good. The total forward volume, total backward volume and regurgitant fraction measured by 2D flow and 4D flow reached a good agreement (ICC=0.954, 0.913,0.721,respectively,P<0.001). The consistency was good for severity of regurgitation measured by 2D flow (weighted Kappa=0.897, P<0.001) and 4D flow (weighted Kappa=0.710, P=0.001) compared with echocardiography. Significant correlation was found among right ventricular cardiac index(r=0.600, P<0.05), right ventricular end-diastolic volume index(r=0.788, P<0.05), right ventricular end-systolic volume index(r=0.683, P<0.05) and left ventricular end-diastolic volume index(r=0.578, P<0.05), left ventricular end-systolic volume index(r=0.687, P<0.05) with regurgitant fraction measured by 2D flow. Regurgitant fraction measured by 4D flow had a significant correlation with right ventricular cardiac index(r=0.606, P<0.05), right ventricular end-diastolic volume index(r=0.685,P<0.05), right ventricular end-systolic volume index(r=0.534, P<0.05) and left ventricular end-diastolic volume index(r=0.459, P<0.05), left ventricular mass index(r=0.633, P<0.05). Conclusion 4D flow MRI provides highly reproducible measurements of pulmonary flow on morphology and haemodynamics in patients with repaired ToF compared with 2D flow MRI and echocardiography.

Objective: To detect the methylation status of ribosomal S6 kinase 4 (RSK4)in papillary thyroid carcinoma (PTC)and to study its correlation with mRNA expression and clinical features. Methods: 134 cases PTC tissues and corresponding paracancerous thyroid tissues were collected. DNA methylation status of RSK4 gene in PTC tissues and corresponding paracancerous tissues were analyzed by methylation specific PCR and bisulfite genomic sequencing, and mRNA expression was detected by quantitative realtime PCR. The relationship of DNA methylation status with mRNA expression and clinical features was analyzed. Results: The methylation rate of RSK4 in PTC tissues was significantly higher than that in paracancerous tissues by methylation specific PCR (P<0.05)and bisulfite genomic sequencing (P<0.01). The RSK4 mRNA level in PTC tissues was significantly lower than that in paracancerous tissues (P<0.01). In PTC tissues, RSK4 mRNA expression in methylation group was lower than that in unmethylation group (P<0.01). The RSK4 mRNA level in PTC of methylation was lower than that in paracancerous tissues of methylation (P<0.01); the RSK4 mRNA level in PTC of unmethylation was also lower than that in paracancerous tissues of unmethylated ones (P<0.01). There was relationship of RSK4 hypermethylation with lymphatic metastasis and TNM grade (P<0.05). Serum concentrations of thyroid stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody in methylation group were higher than those in unmethylation group (P<0.05). Conclusion The hypermethylation of RSK4 promoter′s CpG islands might be one of the mechanisms for poor expression of RSK4 in PTC, which may serve as a molecular target of early diagnosis and treatment.