Atherosclerosis is a chronic vascular disease,whose early manifestations are vascular intimal hyperplasia and plaque formation,and the late vascular events can be caused by plaque rupture after erosion.In the process of ather-osclerosis,vascular smooth muscle cell(VSMC)in the arterial media play a key role in vascular remodeling,and their phe-notype conversion has an important impact on maintaining vascular homeostasis.Due to methodological limitations,the previous understanding of VSMC function is limited;With the rapid development of lineage tracing and single-cell sequen-cing technology,the role of VSMC in atherosclerosis has been deeply explored in recent years.This paper summarizes the emerging research methods of VSMC in recent years,and reviews the literature on the roles and mechanisms of phenotypic switching of VSMC in vascular remodeling.

Atherosclerosis is a chronic vascular disease,whose early manifestations are vascular intimal hyperplasia and plaque formation,and the late vascular events can be caused by plaque rupture after erosion.In the process of ather-osclerosis,vascular smooth muscle cell(VSMC)in the arterial media play a key role in vascular remodeling,and their phe-notype conversion has an important impact on maintaining vascular homeostasis.Due to methodological limitations,the previous understanding of VSMC function is limited;With the rapid development of lineage tracing and single-cell sequen-cing technology,the role of VSMC in atherosclerosis has been deeply explored in recent years.This paper summarizes the emerging research methods of VSMC in recent years,and reviews the literature on the roles and mechanisms of phenotypic switching of VSMC in vascular remodeling.

In recent years, artificial intelligence (AI) has been widely applied in the field of drug discovery and development.In particular, natural language processing technology has been significantly improved after the emergence of the pre-training model.On this basis, the introduction of graph neural network has also made drug development more accurate and efficient.In order to help drug developers more systematically and comprehensively understand the application of artificial intelligence in drug discovery, this article introduces cutting-edge algorithms in AI, and elaborates on the various applications of AI in drug development, including drug small molecule design, virtual screening, drug repurposing, and drug property prediction, finally discusses the opportunities and challenges of AI in future drug development.

OBJECTIVE To study the unknown impurity in potassium aspartate and magnesium aspartate injection by heart-cutting two-dimensional liquid chromatography coupled with Quadrupole time-of-flight mass spectrometry (2D-LC-Q-TOF-MS). METHODS The Waters ACQUITY UPLC 2D system and Xevo G2-XS QTof-MS system were used. One- dimensional chromatographic conditions were as listed. An Agilent ZORBAX-NH2 column was used, and potassium dihydrogen thophosphate(0.05 mol·L-1)-acetonitrile(37∶63) as the mobile phase, at a flow rate of 1.3 mL·min-1. The detection wavelength was set at 200 nm. Two-dimensional chromatographic conditions were as listed. A Waters ACQUITY UPLC HSS T3 column was used, and 0.1% formic acid solution(ESI+)/5 mmol·L-1 ammonium formate(ESI-) as the mobile phase A, and acetonitrile as the mobile phase B, in gradient mode. The mass spectrometry used an electro spray ionization source(ESI) for positive and negative ion mode detection. RESULTS Combined the high resolution mass, MS2 fragment ions and the UNIFI software, the possible structure of the unknown impurity in potassium aspartate and magnesium aspartate injection was infered. CONCLUSION The 2D-LC-Q-TOF-MS method can be used to identify impurities in potassium aspartate and magnesium aspartate injection, which provides reference for the improvement of quality control and process optimization of potassium aspartate and magnesium aspartate injection.

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABA_A receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/metabolism* ; Humans ; Mice ; Mice, Knockout ; Neurons/metabolism*

Objective:To investigate the epidemiological characteristics of lower extremity deep vein thrombosis (DVT) in patients with femoral fracture.Methods:Retrospectively analyzed were the data of 2,571 patients with femoral fracture who had been treated at the Third Hospital of Hebei Medical University from January 2019 to December 2019. There were 1,079 males and 1,492 females, aged from 14 to 96 years (average, 67.1 years). There were 1,158 femoral neck fractures, 951 femoral intertrochanteric fractures, 309 femoral shaft fractures, and 153 femoral condylar fractures. 2,414 patients were treated surgically while 157 patients non-surgically. Color Doppler ultrasonography of both lower extremities was performed to determine the occurrence of DVT before operation and every week after operation for patients undergoing surgical treatment, and within 48 hours after admission and every week during hospitalization for those undergoing non-surgical treatment. The incidence and location of DVT were recorded for different femoral fractures.Results:The incidence of DVT in this cohort was 35.5%(913/2,517), that of proximal DVT 5.3%(135/2,571), and that of distal DVT 30.3% (778/2,571). In patients with femoral neck fracture, femoral intertrochanteric fracture, femoral shaft fracture and femoral condylar fracture, the incidence of DVT was respectively 28.8% (334/1,158), 44.7% (425/951), 30.7% (95/309) and 38.6% (59/153), the incidence of proximal DVT was respectively 2.7% (31/1,158), 5.6%(53/951), 9.7% (30/309) and 13.7% (21/153), and the incidence of distal DVT was respectively 26.2% (303/1,158), 39.1% (372/951), 21.0% (65/309) and 24.8%(38/153). The incidence of DVT in the femoral vein and above, popliteal vein, tibiofibular vein and intermuscular vein in this cohort was respectively 2.3%(60/2,571), 2.9%(75/2,571), 6.4%(165/2,571) and 23.8%(613/2,571).Conclusions:The incidence of DVT may be high in patients with femoral fracture, and the proximal DVT with a high risk of pulmonary embolism may occur more in patients with femoral condylar fracture.

Objective:To explore the application value of fetal heart quantification (fetal HQ) in evaluation of fetal cardiac function and morphology in fetuses with left ventricular outflow tract obstruction (LVOTO).Methods:Twenty-five fetuses with LVOTO diagnosed by fetal echocardiography in Sir Run Run Shaw Hospital, Zhejiang University Medical College from April to July 2020 were enrolled. The end-diastolic basal apical length(BAL), transverse length (TL), global spherical index (GSI) of fetal four-chamber view, and the left and right ventricular end-diastolic area, long diameter, 24-segment end-diastolic transverse length (ED) and its Z-scores adjusted by gestational age and 24-segment spherical index(SI) were calculated by using fetal HQ. Subsequently the Z-scores of left and right ventricle fractional shortening (FS) in 24 segments were obtained by gestational age.Results:SI of 24-segments of left ventricles in fetuses with LVOTO were significantly different from that of right ventricles (all P<0.05). There was significant difference between left and right ventricular areas ( P<0.05). There was no significant difference between left and right ventricular lengths ( P>0.05). There were significant differences between the 24-segment Z-scores of left and right ventricular ED(all P<0.05). The ratios of RVED to LVED of 24 segments were analyzed by box diagram. The results showed that the transverse length of right ventricle was significantly higher than that of left ventricle. The highest value was 1.49(1.26-1.86), and the lowest value was 1.40(1.26-1.86), both significantly higher than the normal value of 1.19. There were no significant differences between the 1-19-segment Z-scores of left and right ventricular FS( P>0.05). There were significant differences between the 20-24-segment Z-scores of left and right ventricular FS( P<0.05). Conclusions:Fetal HQ can be used to quantitatively analyze left ventricular shape, size and function of fetuses with LVOTO, which provides a new method for quantitative analysis of fetal heart function.

Objective:To explore the feasibility of fetal intelligent navigation echocardiography (FINE) in automatic quantitation of cardiac axis (CA).Methods:A total of 62 pregnant women of which 2 with twins′ pregnancy in the second and third trimesters from May to June 2020 in Sir Run Run Shaw Hospital Zhejiang University College of Medicine were enrolled in this non-selective and prospective study. After excluding those who could not be analyzed, they were assigned into four groups according to their CA measuring methods: ①Group with manual measuring CA in systole (CAS); ②Group with manual measuring CA in diastole(CAD); ③Group with CA measured by FINE in three-steps; ④Group with CA measured by FINE in seven-steps. The CAS among groups were compared in order to analyze the consistency and correlation of CAS achieved by different methods, meanwhile, the intra-observer and inter-observer consistency and repeatability were also evaluated.Results:A total of 64 fetuses with 187 volume data were collected, of which 60 cases of fetal data can be included in the study, 57 cases of normal CA, 3 cases of abnormal CA, a total of 158 volume data can be used for data analysis, the success rate was about 84.5%. Because of the small number of abnormal CA cases (3 cases), only 57 cases of normal CA were statistically analyzed in this study. Three-step and seven-step FINE automatic quantitative CA showed significantly different from those obtained with manual measurements of CAD ( P=0.005, P<0.001). There were no significant differences in quantitative analysis of CA between three-step or seven-step FINE and manual measurements of CAS ( P=0.458, 0.883), however, there was no correlation between CA using three-step FINE and manual measurement of CAS ( rs=0.056, P=0.679), but there was a positive correlation between CA using seven-step FINE and manual measurement of CAS ( rs=0.599, P<0.001). The linear regression equation was constructed as follows: Y=10.96+ 0.73 X ( R2=0.431, P<0.001). There was no correlation between three-step method and seven-step method for automatic quantitative CA ( rs=0.158, P=0.241). There was significant difference( P<0.001), but strong correlation between manual measurement of CAS and manual measurement of CAD ( rs=0.973, P<0.001), the average difference was ΔCA=(4.5± 3.8)°. The linear regression equation was constructed as follows: Y=-2.94+ 0.96 X ( R2=0.950, P<0.001). Intra-observer and inter-observer measurements had shown no significant difference in consistency and repeatability (all P>0.05). Conclusions:The measurement of fetal CA by seven-step FINE is superior to the three-step FINE when the fetal CA is in normal range. This may be considered a promising aspect that seven-step FINE automatic quantitation of fetal CA can replace the manual measurement of CAS. Future research is needed to deliminate the reliability of automatic quantification of fetal CA by seven-step FINE with the CA in abnormal range.

Objective To evaluate the short-term efficacy of total hip arthroplasty combined with subcutaneous osteotomy in the treatment of CroweⅣ hip dysplasia (DDH).Methods From March 2012 to March 2015,14 patients (16 hips) underwent total hip arthroplasty with femoral distraction osteotomy S-ROM femoral stem prosthesis.And we observed its recent efficacy.Results All patients underwent S-ROM prosthesis.The patients underwent transverse osteotomy of the femoral trochanter.The osteotomy length was 2.0-3.5 cm.The average follow-up time was 19 months.And no complications such as dislocation,vascular nerve injury,deep vein thrombosis and infection were observed during the follow-up.The average Harris scores improved from 42.3 preoperatively to 90.4 postoperatively at 9 months after the operation.The average lengths of preoperative limb shortening and postoperative limb shortening were 6.4 cm and 4.3 cm respectively.The X-ray films showed no dislocation of acetabulum and femoral prosthesis.Bone healing was achieved at 6 months after osteotomy.Conclusion This method could be a good choice for Crowe Ⅳ developmental dysplasia.The short-term efficacy is satisfactory.