Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

The recording and analysis of activities of calcium signals in neurons is of critical importance in the field of neuroscience.Over the past three decades,various fluorescent calcium imaging techniques not only have been used in the imaging study of functional activities of neuronal communities,but also can be combined with specific markers to record the functional activities of specific types of neuronal communities.To analyze neural activities at the cellular level,a series of preprocessing such as motion correction,cell body recognition,calcium signal extraction and peak deconvolution is required for the collected video.However,current methods for manual preprocessing are time-consuming and laborious,so computer automatic analysis technology is urgently needed to quickly repair the jitter in the video,identify the position and outline of a single cell,extract its activity trajectory and infer the action potential peak.In this paper,the methods of calcium imaging data processing used in recent years are summarized,and the future developments are predicted.

Objective To build a neural network based on the Unet infrastructure for recognition and segmentation of two-dimensional calcium imaging fluorescence images.Methods The in vivo miniaturized two-photon microscope(mTPM)was used for brain calcium imaging in freely moving mice.The imaging data was motion corrected using the NoRMCorre algorithm and processed using ImageJ software to obtain the original images after correction,and the labels were produced using the Labelme software.The neural network HDCGUnet was built using the original images and labels for training,and optimized to improve the model structure according to the training effect.Finally,the evaluation indexes were selected and compared with those of other models to verify the utility of this model.Results The HDCGUnet model,which was collected and made on our own,performed best in the two-photon calcium imaging dataset compared to other models,and performed well on the BBBC dataset either.Conclusion The HDCGUnet model provides a novel alternative for the recognition and segmentation of two-photon calcium imaging images.

Objective To observe the effectiveness and safety of different methods under multi-disciplinary treatment(MDT)model for treating pulmonary arteriovenous malformation(PAVM).Methods MDT were retrospectively performed in 31 patients with PAVM.The effectiveness and safety of interventional therapy,surgical treatment and conservative therapy for PAVM were compared.Results Among 31 cases of PAVM,22 cases underwent interventional therapies(interventional group),4 cases received surgical treatments(surgical group)and 5 cases underwent conservative therapies(conservative group).In interventional group,PAVM was successfully embolized in all 22 cases,with the technical success rate was 100％(22/22).Pleurisy was occurred in 3 cases(3/22,13.64％),while recurrence of PAVM was noticed in 4 cases(4/22,18.18％)during follow-up.No recurrence occurred in interventional group after the second interventional therapies.In surgical group,4 cases were successfully treated with thoracoscopic lobectomy,with the technical success rate of 100％(4/4).No postoperative complication occurred,while recurrence of PAVM was noticed in 2 cases(2/4,50.00％)during follow-up,including 1 case underwent interventional therapy and 1 case underwent conservative therapy.In conservative group,progressive PAVM was observed in 3 cases(3/5,60.00％),including 2 cases who were cured with interventional therapy and 1 case died of stroke after conservative therapy.Conclusion Individualized treatments of PAVM were feasible under MDT model.Compared with surgical treatments and conservative therapies,interventional therapies of PAVM were more effective and relatively safe.

Objective To analyze the antihypertensive compliance rate,drug use and complication distribution among very old hypertensive inpatients under the antihypertensive standard of 150/90 mm Hg in our country(1 mm Hg=0.133 kPa).Methods A total of 409 hospitalized patients aged ≥80 years and diagnosed with hypertension in all departments of Air Force Medical Center of PLA were enrolled,and according to their clinical outcomes,they were divided into intensive antihypertensive group(106 cases,SBP＜130 mm Hg),standard antihypertensive group(155 ca-ses,SBP 130-149 mm Hg)and non-standard blood pressure group(148 cases,SBP ≥150 mm Hg).The status of blood pressure control was analyze in each group.Results When 150/90 mm Hg was used as the blood pressure standard,25.9％were in the intensive blood pressure group,37.9％were in the standard blood pressure group,36.2％were in the non-standard blood pressure group.The proportion of patients aged＞90 years was significantly lower in the non-standard blood pressure group than the intensive antihypertensive group and the standard anti-hypertensive group(4.1％vs 7.5％and 12.3％,P＜0.05).The ratio of single-drug therapy was significantly higher in the standard antihypertensive group than the intensive antihypertensive group(46.5％vs 32.1％,P＜0.05),and that of dual combination therapy was obviously higher in the intensive antihypertensive group than the standard antihypertensive group(35.8％vs 22.6％,P＜0.05).The proportions of heart damage and cerebrovascular damage were significantly higher(43.4％vs 21.9％,26.4％vs 14.8％),and the proportion of complicated retinopathy was notably lower(11.3％vs 23.9％)in the intensive antihypertensive group than the standard antihypertens-ive group(P＜0.05).Conclusion For very old hypertensive patients in our country,it is more sci-entific and practical to use 150/90 mm Hg as the starting standard for blood pressure reduction.Intensified blood pressure reduction increases cardiovascular and cerebrovascular damages in them instead.

Objective:To analyze the correlation between peripheral blood lymphocyte subsets, especially B cells, and the relapse of autoimmune encephalitis (AE).Methods:A retrospective analysis was conducted on patients with AE who were diagnosed and treated in Peking Union Medical College Hospital from January 2012 to January 2023. The clinical data including gender, age and changes in related indicators of CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells, CD8 +T cells, IgG, IgA, and IgM before and after recurrence were analyzed.Binary Logistic regression analysis was applied to the study of correlation between AE recurrence and gender, age, CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells, CD8 +T cells, IgG, IgA and IgM. The receiver operating characteristic (ROC) curves of the cells that affect AE recurrence (CD19 +B cells, CD16/56 +NK cells, CD3 +T cells, CD4 +T cells and CD8 +T cells) were plotted separately. Results:A total of 198 eligible AE patients were included, including 98 males and 100 females, aged (39.52±17.91) years. Among these patients, 78 cases had relapses, with a recurrence rate of 39.4%. The results of Logistic regression analysis showed that CD19 +B cells ( B=0.006, P<0.001), CD16/56 +NK cells ( B=0.004, P<0.05), CD3 +T cells ( B=-0.011, P<0.05), CD4 +T cells ( B=0.014, P<0.05) and CD8 +T cells ( B=0.010, P<0.05) were highly correlated with the relapse of AE. ROC curve analysis showed that CD19 +B cells (area under the curve: 0.833, P<0.001, critical value: 73.5/μl; sensitivity: 69.2%, specificity: 86.7%), CD3 +T cells (area under the curve: 0.784, P<0.001), CD4 +T cells (area under the curve: 0.808, P<0.001), and CD8 +T cells (area under the curve: 0.742, P<0.001) all had a certain predictive value for AE relapse. Among all the indicators, the area under the curve of CD19 +B cells was the largest, which had a higher value in predicting AE recurrence. Conclusion:The increase in peripheral blood CD19 +B cells has high predictive value for the relapse of AE.

Objective:To explore the application value of quantitative flow ratio (QFR) in the hemodynamic evaluation of myocardial bridge and to preliminarily evaluate the correlation and related influencing factors between deformation quantitative flow ratio (D-QFR) and QFR.Methods:This is a cross-sectional study. Patients with CAG-confirmed simple myocardial bridge of the middle anterior descending coronary artery from June 2012 to June 2022 at the Air Force Medical Center were retrospectively included in this study. Systolic stenosis of mural coronary arteries (MCA) and myocardial bridge length were measured using quantitative coronary angiography. The patients were divided into mild stenosis group (<50% systolic stenosis) and moderate-to-severe stenosis group (≥50% systolic stenosis) according to the Nobel grading criteria. At different time periods (systolic and diastolic), the QFR values were measured at 3 locations (1 to 2 cm before the MCA entrance, the middle segment of the MCA, and 1 to 2 cm after the MCA exit), denoted as QFRa, QFRb, and QFRc, respectively, and the D-QFR values, incorporating vessel deformation information, were recorded. The MCA distal QFR≤0.8 in either stage was defined as an abnormal QFR value. QFR values were compared between the two groups at different locations and within each group. Factors associated with abnormal QFR values were analysed using multifactorial logistic regression. Spearman rank correlation analysis was used to examine the correlation between D-QFR values and systolic and diastolic QFR values.Multiple linear regression was used to analyse the factors associated with D-QFR.Results:A total of 83 patients were enrolled, including 58 males, aged (57.1±13.1) years. There were 48 cases in the mild stenosis group and 35 cases in the moderate-to-severe stenosis group, and the differences in systolic and diastolic QFRb and QFRc values between the two groups were statistically significant (all P<0.05). Within-group comparisons showed the values of QFRb and QFRc in the systolic phase were lower than those in the diastolic phase; QFRb and QFRc were both lower than QFRa during the same period (all P<0.05). Multifactorial logistic regression analysis showed that MCA systolic stenosis ( OR=1.225, 95% CI 1.093-1.372, P<0.001) was an influential factor for abnormal QFR. D-QFR values were positively correlated with both systolic and diastolic QFR values (correlation coefficients were 0.849 and 0.675, respectively, both P<0.01). Multiple linear regression analysis showed that D-QFR values were negatively correlated with age ( β=-0.208, P=0.029), systolic stenosis ( β=-0.500, P<0.001), and myocardial bridge length ( β=-0.211, P=0.036). Conclusions:The QFR values in middle and distal of myocardial bridge decrease. The systolic stenosis rate of myocardial bridge is an important factor affecting QFR value. D-QFR is positively correlated with both systolic and diastolic QFR values. Age, myocardial bridge systolic stenosis rate and length are factors influencing the D-QFR values.

Objective To examine the regulation of malignant progression of colorectal cancer by LINC00626 via the JAK1/STAT3/KHSRP signaling axis and its molecular mechanism.Methods 96 individuals diagnosed with colorectal cancer at our hospital during June 11,2021 and June 11,2023 were chosen as research subjects,and their cancerous tissue and nearby normal tissue were collected.Cultivate colorectal cancer cell lines(SW620,HCT116,HT29,DLD-1,LOVO,Caco-2)and normal colorectal cells(NCM460)in vitro,and detect the expression of LINC00626 and KHSRP in colorectal cancer tissue and cell lines using qRT-PCR.Screening out cell lines infected with lentivirus,SW620 and HCT116 cell lines were transfected with knockdown lentivirus and its control,while HT29 and DLD-1 cell lines were transfected with overexpressing lentivirus and its control,respectively.Select stable transfected cell lines for cell function experiments to detect proliferation,migration,and invasion abilities.Detection of the effect of LINC00626 on the growth and migration of colorectal cancer tumors in live mouse experiments.The expression level of KHSRP protein in stable labeled cells was determined using a western blot analysis.Rescue experimental research on the regulatory relationship between LINC00626 and KHSRP.Results qRT-PCR showed low expression of LINC00626 and high expression of KHSRP in colorectal cancer tissues and cell lines.Cell function experiments showed that compared with the sh-NC group,the sh-LINC00626 group promoted cell proliferation,migration,and invasion in SW620 and HCT116 cells,while the overexpression group showed the opposite.Cell rescue experiments showed that,LINC00626+KHSRP significantly reversed the promotion effects of knocking down LINC00626 on cell proliferation,migration,and invasion.In the nude mouse experiment,com-pared with the sh-NC group,the sh-LINC00626 group showed a significant increase in tumor volume and weight,cell proliferation rate,and the number of lung metastases from colorectal cancer in the nude mice;Overexpression results in the opposite.The signal pathway experiment revealed that relative to the sh-NC group,the expression levels of JAK1 and STAT3 mRNA in the sh-LINC00626 group were significantly increased,whereas the results in the overexpression group were the opposite.Conclusion LINC00626 suppression the malignant progression of colorec-tal cancer metastasis through the JAK1/STAT3/KHSRP signaling axis.

Objective To perform structural analysis on the homogeneous polysaccharide SP800301 isolated from Saposhnikoviae Radix to determine its chemical structure.Methods Polysaccharides were separated and purified from Saposhnikoviae Radix using column chromatography,such as DEAE-cellulose and Sephadex G-75.The molecular weight distribution,monosaccharide composition,oligosaccharide fragments,sugar residue types,and glycosidic bond connection of the isolated homogeneous polysaccharide SP800301 from Saposhnikoviae Radix were analyzed using electrospray ionization multistage mass spectrometry,gas chromatography-mass spectrometry,and nuclear magnetic resonance to determine its structure.The appearance characteristics of the Saposhnikoviae Radix polysaccharide were characterized using electron and atomic force microscopy.Results Polysaccharide SP800301 extracted from Saposhnikoviae Radix had good homogeneity with a molecular weight of 9.1×104 g/mol.The uronic acid content was 52.72%.The monosaccharide group comprised rhamnose,galacturonic acid,glucose,galactose,and arabinose,with a molar ratio of 4.3:58.1:25.4:5.0:7.3.The polysaccharide was mainly composed of polygalacturonic acid as the primary chain.The branched chain was comprised of rhamnose,galacturonic acid,galactose,glucose,and arabinose,with arabinose at the end of the branched chain and part of the galacturonic acid in the sugar chain forming a methyl ester.Conclusion This study clarified the chemical structure of the homogeneous polysaccharide SP800301 from Saposhnikoviae Radix,enriched the chemical composition of Saposhnikoviae Radix polysaccharides,laid the foundation for further research on the immune regulatory mechanism of Saposhnikoviae Radix polysaccharides,and provided a scientific basis for clinically using Saposhnikoviae Radix.

Objective With the increase in pet-owning households in China, veterinary clinics have increased at an annual rate of 19.86%. However, the management blind area that may exist in multi-department supervision has led to a significantly worse working environment of radiation workers in veterinary clinics than that of medical institutions. The purpose of this study was to understand the levels of occupational external exposure of radiation workers in veterinary clinics in China, analyze the occupational risks faced by radiation workers in veterinary clinics, contribute to the protection of the occupational health of radiation workers, and provide data and scientific basis for the formulation of national relevant regulations and standards. Methods The individual dose monitoring data of radiation workers in selected veterinary clinics in 2022 were obtained from the National Individual Dose Registration System. Results This study involved 1868 radiation workers from 1216 veterinary clinics in 28 provinces and municipalities in China. The maximum annual effective dose was 8.93 mSv, the annual collective dose was 536.77 man·mSv, the average annual effective dose was 0.29 mSv, and the median was 0.15 mSv. The largest proportion of individuals (94.5%) received a dose of less than 1.0 mSv, while 5.4% had doses ranging from 1.0 mSv to less than 5.0 mSv. For radiation workers with an annual effective dose of 1.0 mSv and above, the individual distribution ratio of radiation workers in veterinary clinics was significantly higher compared with those in medical institutions and industrial applications (P < 0.05). Conclusion The levels of occupational external exposure of radiation workers in veterinary clinics meet the requirements of national standards. However, attention should still be paid to the radiation protection of radiation workers in veterinary clinics. This includes enhancing the responsibility awareness of veterinary clinic owners, strengthening protection training for radiation workers, protecting the occupational health of practitioners, and preventing the occurrence of occupational radiation diseases.