Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

Objective:pH low insertion peptide (pHLIP)-variant 7 (var7)-fluorescein isothiocyanate (FITC) was used to explore an accurate imaging tool that targeted burn wounds to better perform burn debridement.Methods:Twelve rat models of burn wound were established and pHLIP-var7-FITC with different concentrations (0.5, 1.5 and 2.0 mg/ml) were injected from the rat tail vein for in vivo fluorescence imaging. By determining the concentration of fluorescent conjugates to the burn wound, the scope of wound injury necrosis was judged by combining pathological sections, and its residue and toxicity in important organs such as heart, liver, kidneys, and brain were detected. The Kruskal-Wallis rank sum test, Bonferroni correction method and one-way analysis of variance were used for data analysis. Results:Within 24 h, the fluorescence photons per unit area of the burn wound in the group of 0.5 mg/ml, 1.5 mg/ml and 2.0 mg/ml were 1.49(1.31, 1.65), 2.46(1.88, 2.68), 2.77 (1.94, 3.10)×10 7 p·s -1·cm -2·Sr -1, with significant differences in the overall distribution of fluorescence photons ( H=73.55, P<0.001). The fluorescence intensity was stronger in the group with higher concentration, but with no significant difference in the number of fluorescence photons between the group of 1.5 mg/ml and 2.0 mg/ml ( P=0.263, Bonferroni correction method). At 14 time points (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 7.0, 8.0, 12, 24 h), there was no significant difference in the overall mean of fluorescence photons ( F=1.04, P=0.419), and the tissue with burn necrosis seen in tissue sections was highly consistent with the fluorescence imaging region. There was no obvious fluorescence residue in the heart, liver, kidney and brain sections. Conclusion:In superficial second-degree burn tissue, pHLIP-var7-FITC can accurately target and gather on the burn wound within 24 h, showing a clear boundary between burn tissue and normal tissue, which can assist clinical surgical debridement to determine the extent of injury.

Objective:To investigate the clinical outcome of endovascular treatment vs. drug treatment in patients with symptomatic non-acute long-segment occlusion of the internal carotid artery. Methods:Based on prospective cohort registration research data, patients with symptomatic non-acute long-segment occlusion of internal carotid artery were retrospectively included. They were divided into a drug treatment group and an endovascular treatment group according to the actual treatment received. The latter was further divided into a successful recanalization group and an unsuccessful recanalization group. The endpoint events included ipsilateral ischemic stroke, any stroke, and all-cause death. Multivariate logistic regression analysis was used to compare the endpoint events between groups during the perioprocedural period (within 30 days), and multivariate Cox proportional hazards model was use to compare the endpoint events between the groups during the long-term follow-up. Results:A total of 684 patients were included, of which 570 (83.33%) were male, median aged 63 years (interquartile range, 56-70 years). Three hundred and fifty-three patients (51.6%) received drug treatment; 331 (48.4%) received endovascular treatment, of which 161 (48.6%) had successful recanalization. The median follow-up time was 1 223 days (interquartile range, 646.5-2 082 days), with 109 patients (15.9%) experiencing stroke recurrence events (including 87 ipsilateral ischemic stroke) and 78 (11.4%) experiencing all-cause mortality. The risk of any stroke during the perioprocedural period in the successful recanalization group was significantly higher than that in the drug treatment group (odds ratio 3.679, 95% confidence interval 1.038-13.036; P=0.044), but the risk of ipsilateral ischemic stroke recurrence (risk ratio 0.347, 95% confidence interval 0.152-0.791; P=0.012) and all-cause mortality (risk ratio 0.239, 95% confidence interval 0.093-0.618; P=0.003) during the long-term follow-up were significantly lower than those in the drug treatment group. Conclusions:In patients with symptomatic non-acute long-segment occlusion of the internal carotid artery, endovascular treatment can increase the risk of stroke recurrence within 30 days, but successful recanalization can reduce the risks of long-term ipsilateral ischemic stroke recurrence and all-cause mortality.

Objective:To investigate predictive factors for successful endovascular recanalization in patients with non-acute symptomatic internal carotid artery occlusion (SICAO), to develop a decision tree model using the Classification and Regression Tree (CART) algorithm, and to evaluate the predictive performance of the model.Methods:Patients with non-acute SICAO received endovascular therapy at 8 comprehensive stroke centers in China were included retrospectively. They were randomly assigned to a training set and a validation set. In the training set, the least absolute shrinkage and selection operator (LASSO) algorithm was used to screen important variables, and a decision tree prediction model was constructed based on CART algorithm. The model was evaluated using the receiver operating characteristic (ROC) curve, Hosmer-Lemeshow goodness-of-fit test and confusion matrix in the validation set.Results:A total of 511 patients with non-acute SICAO were included. They were randomly divided into a training set ( n=357) and a validation set ( n=154) in a 7:3 ratio. The successful recanalization rates after endovascular therapy were 58.8% and 58.4%, respectively. There was no statistically significant difference ( χ2=0.007, P=0.936). A CART decision tree model consisting of 5 variables, 5 layers and 9 classification rules was constructed using the six non-zero-coefficient variables selected by LASSO regression. The predictive factors for successful recanalization included fewer occluded segments, proximal tapered stump, ASITN/SIR collateral grading of 1-2, ischemic stroke, and a recent event to endovascular therapy time of 1-30 d. ROC analysis showed that the area under curve of the decision tree model in the training set was 0.810 (95% confidence interval 0.764-0.857), and the optimal cut-off value for predicting successful recanalization was 0.71. The area under curve in the validation set was 0.763 (95% confidence interval 0.687-0.839). The accuracy was 70.1%, precision was 81.4%, sensitivity was 63.3%, and specificity was 79.7%. The Hosmer-Lemeshow test in both groups showed P>0.05. Conclusion:Based on the type of ischemic event, the time from the latest event to endovascular therapy, proximal stump morphology, the number of occluded segments, and the ASITN/SIR collateral grading constructed the decision tree model can effectively predict successful recanalization after non-acute SICAO endovascular therapy.

Objective:To retrospectively analyze the gender differences in the clinical characteristics and perioperative outcomes of patients with type A aortic dissection in our institution.Methods:From January 2019 to January 2020, total 405 patients underwent surgical treatment for type A aortic dissection at Beijing Anzhen Hospital, including extensive aortic repair (total aortic arch replacement combined with stenting elephant trunk implantation) and limited aortic repair. In the entire cohort, male 295 cases, female 110 cases. All measures in this study were expressed as ± s or median(quartiles) and analyzed by Student t test for variables or non- parametric tests; count data were expressed as frequencies and percentages and analyzed by χ2 test and Fisher exact probability test. Independent risk factors were analyzed by logistic multivariate regression. Results:Females were older than males[(53.3 ± 12.4)years old vs. (47.1 ± 11.0)years old, P<0.001] and had significantly higher proportion of diabetes(9.1% vs. 4.1%, P=0.047) and previous cerebrovascular disease (11.8% vs. 5.8%, P=0.038). Females had a lower proportion of total aortic arch replacement combined with elephant trunk implantation (64.5% vs. 82.7%, P<0.001), while aortic cross-clamp time[168.0(144.8, 201.5) minutes vs. 190.0 (163.0, 217.0) minutes, P<0.001] and CPB time[99.0 (79.8, 118.0) min vs. 107.0 (91.0, 126.0) min, P=0.006] were significantly shorter than males. Females had significantly higher rates of pulmonary infection (14.5% vs. 5.8%, P=0.004) and stroke than males (15.5% vs. 8.1%, P=0.030). The difference in the proportion of postoperative deaths between female and male TAAD patients was not statistically significant (3.6% vs. 7.8%). Logistics multivariable regression analysis found that female was an independent risk factor for postoperative stroke ( OR=2.574, 95% CI: 1.198-5.531, P=0.015) and pulmonary infection ( OR=2.610, 95% CI: 1.180-5.772, P=0.018). Conclusion:Gender did not affect mortality after TAAD repair significantly, but females increased the risk of stroke and pulmonary infection after TAAD surgery.

Objective:To analyze the effect of different lithotomy positions on hemodynamics in patients undergoing laparoscopic total hysterectomy.Methods:A total of 50 patients who underwent laparoscopic total hysterectomy at Zhoushan Women and Children's Hospital between January 2020 and June 2021 were included in this study. The patients were randomly divided into a control group and an observation group using a random number table method, with 25 patients in each group. The control group underwent conventional lithotomy position total laparoscopic hysterectomy, while the observation group underwent high and low lithotomy position total laparoscopic hysterectomy. The general surgical indicators, respiratory function indicators, blood gas analysis indicators, hemodynamic levels, incidence of complications, and clinical efficacy were compared between the two groups.Results:The general surgical indicators and airway peak pressure indicators in the observation group were significantly lower than those in the control group (both P < 0.05). There was no statistically significant difference in partial pressure of end-tidal carbon dioxide (PCO 2) and arterial carbon dioxide partial pressure (PaCO 2) between the two groups (both P < 0.05). At 15 minutes after pneumoperitoneum, the PaCO 2 level increased in each group, and the PaCO 2 level in the observation group was significantly higher than that in the control group (all P < 0.05). At the same time, the HCO 3- level decreased in each group, and the HCO 3- level in the observation group was significantly lower than that in the control group (all P < 0.05). At 5 minutes before recovery of body position, heart rate, systolic blood pressure, and diastolic blood pressure in the control group were (76.52 ± 8.61) beats/minute, (113.52 ± 5.36) mmHg (1 mmHg = 0.133 kPa), and (86.91 ± 4.21) mmHg, respectively. At 5 minutes after recovery of body position, heart rate, systolic blood pressure, and diastolic blood pressure in the control group were (89.52 ± 8.61) beats/minute, (106.85 ± 5.63) mmHg, and (80.96 ± 3.65) mmHg, respectively. At 5 minutes before recovery of body position, heart rate, systolic blood pressure, and diastolic blood pressure in the observation group were (76.36 ± 8.61) beats/minute, (112.79 ± 5.28) mmHg, and (86.89 ± 4.54) mmHg. At 5 minutes after recovery of body position, heart rate, systolic blood pressure, and diastolic blood pressure in the observation group were (75.63 ± 6.86) beats/minute, (111.99 ± 5.51) mmHg, and (85.06 ± 3.21) mmHg, respectively. At 5 minutes after recovery of body position, heart rate in the control group was increased and that in the observation group was decreased compared with heart rate measured at 5 minutes before recovery of body position. At 5 minutes after recovery of body position, heart rate in the observation group was significantly lower than that in the control group. Diastolic blood pressure and systolic blood pressure decreased in each group, and the amplitudes of reductions in diastolic blood pressure and systolic blood pressure in the observation group were significantly lower than those in the control group. ( t = 6.04, 3.26, 4.22, all P < 0.05). There was no statistically significant difference in incidence of adverse reactions between the two groups ( P > 0.05). The overall response rate in the observation group was significantly higher than that in the control group ( P < 0.05). Conclusion:Compared with conventional lithotomy position total laparoscopic hysteretsotomy, high and low lithotomy position total laparoscopic hysterectomy takes a shorter duration for total laparoscopic hysterectomy, leads to a shorter length of hospital stay, results in less blood loss, causes fewer postoperative infections, and results in more stable hemodynamics and a lower incidence of complications.

Brain functional network changes over time along with the process of brain development, disease, and aging. However, most of the available measurements for evaluation of the difference (or similarity) between the individual brain functional networks are for charactering static networks, which do not work with the dynamic characteristics of the brain networks that typically involve a long-span and large-scale evolution over the time. The current study proposes an index for measuring the similarity of dynamic brain networks, named as dynamic network similarity (DNS). It measures the similarity by combining the "evolutional" and "structural" properties of the dynamic network. Four sets of simulated dynamic networks with different evolutional and structural properties (varying amplitude of changes, trend of changes, distribution of connectivity strength, range of connectivity strength) were generated to validate the performance of DNS. In addition, real world imaging datasets, acquired from 13 stroke patients who were treated by transcranial direct current stimulation (tDCS), were used to further validate the proposed method and compared with the traditional similarity measurements that were developed for static network similarity. The results showed that DNS was significantly correlated with the varying amplitude of changes, trend of changes, distribution of connectivity strength and range of connectivity strength of the dynamic networks. DNS was able to appropriately measure the significant similarity of the dynamics of network changes over the time for the patients before and after the tDCS treatments. However, the traditional methods failed, which showed significantly differences between the data before and after the tDCS treatments. The experiment results demonstrate that DNS may robustly measure the similarity of evolutional and structural properties of dynamic networks. The new method appears to be superior to the traditional methods in that the new one is capable of assessing the temporal similarity of dynamic functional imaging data.
Aging/physiology* ; Brain/physiology* ; Brain Mapping ; Humans ; Magnetic Resonance Imaging/methods* ; Nerve Net/physiology* ; Transcranial Direct Current Stimulation/methods*

Objective:To analyze the long-term outcomes of hybrid arch repair(HAR) treating aortic arch pathologies.Methods:Between January 2009 and January 2018, 87 consecutive patients underwent HAR for aortic arch pathologies at Beijing Anzhen Hospital. 76 were males. 2 cases were in zone 0, 46 cases were in zone 1, and 39 cases were in zone 2. The zones of the aortic arch were defined following the Ishimaru classification.Results:Five(5.7%) operative death occurred. 13 patients(19.1%) died during the follow-up. The overall survival rate was 88.4%, 83.3%, 83.3%, 49.8% at 1, 3, 5, 10 year, respectively. Multivariate Cox proportional risk analysis showed that stroke( HR=20.626, 95% CI: 2.698-157.685, P=0.004) was an independent risk factor for short-term death. Stroke( HR=16.234, 95% CI: 4.103-64.229, P<0.001) and spinal cord infury( HR=11.060, 95% CI: 2.150-56.893, P=0.004) were independent risk factors for long-term death. Conclusion:In conclusion, HAR could be an alternative procedure for the patients that are not suitable for open repair under the premise of strict control of indications. In the future, the risk assessment system and uniform operational indications for HAR should be further established.

Objective:To evaluate the radiation dose to the injured persons in a radiological accident, provide the guidance on the diagnosis and treatment of radiation injury, and provide the basis for determination of the level of radiological accident.Method:Firstly, the air-absorbed dose rates at 206 locations surrounding a X-ray device were measured by using LiF (Mg, Cu, P) thermoluminescence detectors and self-made radiation field measuring frames. Secondly, the spatial distribution of radiation level was obtained by fitting the inverse square law between absorbed dose rate and distance, which is used as the basis of dose estimation. Finally, based on the actual working conditions of injured operators, a parameter calculation method was proposed for estimating hand skin absorbed dose.Results:The air-absorbed dose rate surrounding X-ray beam outlet was higher than 1.0 mGy/h. The maximum air-absorbed dose rate value in the space of within 200 cm outside X-ray beam outlet was 262 μGy/h and the minimum value was 2.1 μGy/h, 2 orders of magnitude higher than environmental background level. During normal operation, the total absorbed doses to the hand skin of two injured female operators were 36.9 and 16.9 Gy, respectively. During extreme operation, the hand skin-received total absorbed doses to the two operators were 85.2 and 38.9 Gy, respectively. Under the occupational health standard GBZ 106-2020, the two persons had acute radiation skin injury of grade Ⅲ or Ⅳ on their hands.Conclusions:The results of hand skin exposure doses provide effective support for diagnosis and treatment of radiation injuries and for the determination of radiological accident level. The method used in radiation field reconstruction and dose estimation mentioned in this study can provide reference for the treatment in the similar radiological accident.

Objective:To explore the relationship between CD24 expression in preoperative peripheral blood as well as cancer tissue and clinical parameters and prognosis in patients with hepatocellular carcinoma (HCC) after liver transplantation (LT).Methods:From November 2018 to November 2019, clinical data were collected for 65 HCC patients and 41 patients with benign liver disease.The preoperative peripheral blood level of CD24 was detected by enzyme-linked immunosorbent assay (ELISA) and the expression of CD24 in cancerous foci and adjacent tissues examined by immunohistochemistry.Kaplan-Meier survival curves of differential CD24 expression were plotted and survival differences compared by Log-rank method.One-way ANOVA was utilized for examining the relationship between the expression level of CD24 and various clinicopathological parameters and multivariate Cox analysis for screening independent risk factors affecting patient prognosis.Results:The concentration of CD24 in preoperative peripheral blood (p-CD24) of HCC patients (6.51±2.33 μg/L) was significantly higher than that of patients with benign liver disease (4.10±0.91) μg/L, P<0.05.The positive rate of CD24 was obviously higher in cancerous tissues than that in adjacent tissues (87.7% vs. 4.6%, P<0.05). The peripheral blood level of CD24 was positively correlated with the expression intensity of CD24 in tumor tissues (t-CD24, r=0.570, P<0.001). The expression of CD24 (both in blood and cancer foci) was significantly correlated with preoperative level of gamma-glutamyl transferase (GGT), maximal tumor diameter, microvascular invasion, portal vein tumor thrombus, vessel carcinoma embolus and satellite focus ( P<0.05). The expression of CD24 in patients exceeding the Milan/UCSF criteria was higher than those fulfilling the criteria ( P<0.005). Patients with a higher expression of CD24 had worse overall survival and recurrence-free survival rates as compared to those a lower expression of CD24 ( P<0.05). Multivariate Cox analysis indicated that t-CD24 [OS: HR=3.661(1.005-13.333)], P=0.049; recurrence-free survival (RFS): [HR=4.331(1.887-9.942), P=0.001] and preoperative level of alpha fetoprotein (AFP) [OS: HR=4.900(1.590-15.097), P=0.006]; RFS: [HR=3.414(1.614-7.221), P=0.001] were independent risk factors for overall survival and recurrence-free survival in HCC patients undergoing LT. Conclusions:The preoperative peripheral blood level of CD24 in HCC patients undergoing LT indirectly reflects the expression of CD24 in cancerous tissues to a certain extent.And the expression of CD24 in cancerous tissue is one of the independent risk factors affecting OS and RFS of LT patients.