Objective To investigate the protective effect of umbilical cord mesenchymal stem cells (UCMSCs) on traumatic brain injury (TBI) in rats.Methods Thirty healthy Sprague-Dawley rats (10 rats for each group) were randomly divided into normal control group (normal),model group (injection of saline after TBI) and UCMSCs transplantation group (injection of UCMSCs after TBI).The rats in experimental groups were sacrificed on the 10th day after UCMSCs transplantation.The percentage of UCMSCs in brain tissue was detected by flow cytometry.The pathological changes of brain tissue were observed by hematoxylin-eosin (HE) staining method.The expressions of vascular endothelial growth factor (VEGF),glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor (BDNF) in brain tissue were measured by immunohistochemistry and immunofluorescence double staining.The neurological deficit was evaluated by neurological deficit degree.Results The percentage of CD90,CD73 and CD105 cells in the UCMSCs transplantation group was significandtly higher than that in the model group (0.4％ vs 0.1％,P＜0.05).The results of HE staining showed that the brain injury of the transplanted group was alleviated compared with the model group (P＜0.05).The VEGF of the brain tissue in injury area in the UCMSCs transplantation group was higher than that in the model group (P＜0.05).The number of GFAP and BDNF positive cells in the UCMSCs transplantation group was higher than that in the model group (P＜0.05),and the neurological deficit score was also higher than that in the model group (P＜0.05).Conclusions UCMSCs transplantation for the treatment of TBI rats can effectively reduce the vascular damage in the injury area and promote nerve recovery.

To construct nanostructured lipid carriers(NLCs)with different particle sizes but the same other physicochemical properties, central composite design was adopted. Coumarin-6(C-6)was selected as the model drug due to its high lipophilicity and high fluorescence intensity. Physicochemical properties of NLCs with 100 nm, 200 nm and 300 nm in particle size could remain stable during certain time in K-R solution and PBS. Release experiments in vitro showed that cumulative release of C-6 in NLCs was less than 7% after 24 h. The MTT assay indicated that both blank NLCs and C-6 loaded NLCs showed low toxicity. To confirm the integrity of NLCs in gastrointestinal tract, DiR-loaded NLCs were prepared and the distribution in vivo was monitored by fluorescence imaging. After 6 h oral administration, intact DiR-loaded NLCs could stiu be found, suggesting that NLCs could be used to characterize the uptake in gastrointestinal tract.

Objective To compare the dosimetric characteristics of the methods of volumetric modulated arc therapy ( VMAT ) for craniospinal irradiation , and to compare their robustness to the field placement error . Methods Six patients receiving craniospinal irradiation were included. VMAT plans of each patient were optimized with overlap method and gradient-optimization method respectively using Pinnacle 9.8 VMAT treatment planning system. The length of the overlap region was set as 3 and 9 cm, respectively. Then the dose distributions under different VMAT programs were measured. Moreover, a 3 mm placement error was introduced, and the dose cold spot in the field junction region obtained by each plan was compared for robustness analysis. Results Under different overlapping lengths, the overlap method and the gradient optimization method both can optimize the VMAT plan that meeting the clinical requirements. In the field junction region, the dose distribution obtained by the overlap method was more uniform, and the difference in the uniformity index was statistically significant. When introducing a 3 mm placement error, the gradient optimization method obtained the most robust VMAT plan at 9 cm overlap length, and the overlap method could not obtained stabilized robust plan. Conclusions For the optimization of craniospinal irradiation VMAT plan, the commonly used overlap method can obtain a better dose distribution, but it can't improve robustness by increasing overlap length. However, using the gradient optimization method, the dose homogeneity in the field junction region is not good as the overlap method, but the plan robustness can be improved by increasing the overlap length.

Objective To investigate the supernatant of umbilical cord-derived mesenchymal stem cells (UCMSCs) on tumor necrosis factor-α(TNF-α) and apoptosis protein caspase-3 in diabetic rats model with skin ulcer. Methods 45 Sprague-Dawley rats were randomly divided into control group (acute wounds group), phosphate buffered saline (PBS) group and UCMSCs supernatant group. The diabetic rat model was constructed by injecting with alloxan by tail vein and feeding with high-fat diet. Diabetic skin ulcer (DSU) rat model was constructed by scratching a wound and infusing suspension of Staphylococcus aureus. In the control group, the diabetic rats (n=15) were scratched to form a wound and treated by tail vein injection of 100μl PBS. In the PBS group, DSU rats (n=15) were treated by tail vein injection of 100μl PBS, and then 100μl PBS was dropped at the ulcer site. In the UCMSCs supernatant group, freeze-dried powder of UCMSCs supernatant was dissolved in 200μl PBS, 100μl of which was injected into the tail vein of DSU rats (n=15), and other 100μl was dropped at the ulcer site. After 5 days of the treatments, the levels of serum TNF-αwere detected by radioimmunoassay method, and the expression of TNF-αand caspase-3 in the ulcer tissues of rats was detected by polymerase chain reaction and Western Blot. Results The levels of TNF-αin the PBS group [(35.9±3.7)μg/L] were significantly higher than that of the control group [(11.4±4.9)μg/L] and the UCMSCs group [(14.7±6.6)μg/L] (all P<0.05). The levels of mRNA and protein expression of TNF-αand caspase-3 in the UCMSCs group were significantly lower than those of the PBS group (all P<0.05), and have no significant differences with respect to those of the control group (all P>0.05). Conclusions UCMSCs supernatant treatments can effectively down-regulate the expression of TNF-αand caspase-3 in ulcer tissue of DSU rats, and play an anti-inflammatory and anti-apoptotic effect.

Objective To investigate the effects of human umbilical cord mesenchymal stem cells (UC-MSCs ) on vascular endothelial growth factor ( VEGF ) and monocyte chemoattractant protein-1 ( MCP-1 ) of acute myocardial ischemia-reperfusion (AMI-R) injury in rats. Methods 24 Sprague-Dawley rats were randomly divided into sham group, AMI-R group and UCMSCs treatment groups on average. The rats were sacrificed on the 10th day after UCMSCs transplantation, and the myocardial tissues below the ligature were taken. The mRNA and protein expressions of MCP-1 of the tissue were detected by RT-PCR and Western Blot respectively, and the expression of VEGF protein was detected by immunohistochemistry. Results The relative expression levels of MCP-1 mRNA and the protein in UCMSCs group were significantly lower than those in sham group and AMI-R group (all P<0.05). The expression of VEGF protein in UCMSCs group was significantly higher than that in sham group and AMI-R group, the differences were statistically significant(all P<0.05). Conclusion UCMSCs transplantation can promote the angiogenesis and decrease the inflammation reaction in the treatment of acute myocardial ischemia-reperfusion injury.

Objective:To investigate the conversion of low-energy CBCT images into high-energy CBCT images in clinical radiotherapy based on the deep learning method of U-Net network, in order to provide dual-energy CBCT images and reduce radiation dose.Methods:The CBCT image data of CIRS electron density phantom and CIRS head phantom at 80 and 140 kV were collected by the on-board CBCT in radiotherapy equipment. The dataset was divided into training set and test set according to 10∶1. The U-Net network was used to predict CBCT images at high energy (140 kV) from low-energy (80 kV) CBCT images. Four parameters, including mean absolute error (MAE), structural similarity index (SSIM), signal-to-noise ratio (SNR) and peak signal-to-noise ratio (PSNR) were used to quantitatively evaluate predicted high-energy CBCT images.Results:The overall structural difference between the predicted high-energy image and the real high-energy image was smaller (SSIM: 0.993 ±0.003). The noise of predicted high-energy image was lower (SNR: 15.33±4.06), but there was a loss of inter-tissue resolution. Predicted high-energy images had slightly lower average CT values than real high-energy images, with less difference in low-density tissues (<10 HU, P > 0.05) and greater differences in high-density tissues (<21 HU, t = -7.92, P < 0.05). Conclusions:High-energy CBCT images with high structural similarity can be obtained from energy CBCT images by using deep learning method. The predicted high energy CBCT images have the potential to be applied to clinical dual-energy CBCT imaging technology in radiotherapy.

Objective The 18F-ML-10 PET/CT apoptosis imaging was taken in the early Parkinson's disease (PD) rat models.The feasibility of diagnosis of PD with 18F-ML-10 PET/CT apoptosis imaging is explored.Methods Twenty adult healthy male Sprague-Dawley rats were randomly divided into control group and PD model group (n=l 0).Intrastriat administration of 6-hydroxy dopamine (6-OHDA) was performed to induce progressive and retrograde degenerative changes in the substantial nigra of neurons (PD models).One week after apomorphine inducement,the rotational behaviors of the rats were evaluated.~C-CFT PET/CT imaging and 18F-ML-10 PET/CT were performed to observe the dopamine transport protein expression in the corpus striatum and apoptosis of dopaminergic neurons in the substantia nigra.Immunofluorescence staining of anti-tyrosine hydroxylase (TH) antibody was performed to evaluate the survival of dopaminergic cells in the compact part of substantia nigra.TUNEL was performed to evaluate the apoptosis of dopaminergic cells in the compact part of substantia nigra.Nissl staining was performed to detect the cellular morphology.Results One week after PD modeling,the rats in the experimental group obviously rotated to the contralateral,and the average rotation speed was (4.52 ±1.03) r/min.The ratio of 11C-CFT between the right and left striatum of rats in the experimental group was 0.556±0.017,which was significantly lower than that of the control group (0.998±0.013,P＜0.05).The radioactivity ratio of'8F-ML-10 between the right and left substantia nigra of rats was 1.722±0.083,which was significantly higher than that of the control group (1.024±0.056,P＜0.05).Immunofluorescence showed that the ratio of TH-positive neurons between the right and left compact part of substantia nigra in rats of the experimental group was 0.528 ±0.012,which was significantly lower than that of the control group (1.036±0.030,P＜0.05).TUNEL showed that the number of dopaminergic neuronal apoptosis in the experimental group was 43.200±2.507,which was significantly larger than that of the control group (1.400±0.427,P＜0.05).Conclusion PD is associated with apoptosis of dopaminergic neurons;18F-ML-10 PET/CT imaging can be used to diagnose PD in the early-stage.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.