Objective To explore the efficiency improvement in segmenting neural network with the application of Transformer + U-Net artificial intelligence (AI) and modeling with the application of Python scripts in three-dimensional (3D) printing brachytherapy. Methods A Transformer + U-Net AI neural network model was constructed, and Adam optimizer was used to ensure rapid gradient descent. Computed tomography or magnetic resonance imaging data of patients were standardized and processed as self-made data sets. The training set was used to train AI and the optimal result weight parameters were saved. The test set was used to evaluate the AI ability. Python programming language was used to write an automated script to obtain the output segmentation image and convert it to the STL file for import. The source applicator and needle could be automatically modeled. The time of automatic segmentation and modeling and the time of manual segmentation and modeling were entered by two people, and the difference was verified by paired t-test. Results Dice similarity coefficient (DSC), mean intersection over union (MIOU), and Hausdorff distance (HD95) were used for evaluation. DSC was 0.9341, MIOU was 0.8762, and mean HD95 was 2.516. The mean time of manual segmentation was 1187 s, and the mean time of AI segmentation was 145 s (P < 0.01). The mean time of manual modeling was 321 s, and the mean time of modeling with Python automated scripts was 18 s (P < 0.01). Conclusion The application of Transformer + U-Net automatic segmentation and Python automated scripts can effectively improve work efficiency in the 3D printing brachytherapy for cervical cancer.

BACKGROUND: Previous evidence showed that ambient air pollution and cardiovascular mortality are related. However, there is a lack of evidence towards the modification effect of long-term lifestyle on the association between short-term ambient air pollution and death from cardiovascular events. METHOD: A total of 14,609 death from major adverse cardiovascular events (MACE) were identified among the China Kadoorie Biobank participants from 2013 to 2018. Ambient air pollution exposure including particulate matter 2.5 (PM_2.5), SO₂, NO₂, CO, and O₃ from the same period were obtained from space-time model reconstructions based on remote sensing data. Case-crossover design and conditional logistic regression was applied to estimate the effect of short-term exposure to air pollutants on MACE mortality. RESULTS: We found MACE mortality was significantly associated with PM_2.5 (relative percent increase 2.91% per 10 µg/m³ increase, 95% CI 1.32-4.53), NO₂ (5.37% per 10 µg/m³ increase, 95% CI 1.56-9.33), SO₂ (6.82% per 10 µg/m³ increase, 95% CI 2.99-10.80), and CO (2.24% per 0.1 mg/m³ increase, 95% CI 1.02-3.48). Stratified analyses indicated that drinking was associated with elevated risk of MACE mortality with NO₂ and SO₂ exposure; physical inactivity was associated with higher risk of death from MACE when exposed to PM_2.5; and people who had balanced diet had lower risk of MACE mortality when exposed to CO and NO₂. CONCLUSIONS The study results showed that short-term exposure to ambient PM_2.5, NO₂, SO₂, and CO would aggravate the risk of cardiovascular mortality, yet healthy lifestyle conduct might mitigate such negative impact to some extent.
Humans ; Cardiovascular Diseases/epidemiology* ; China/epidemiology* ; Male ; Female ; Air Pollution/adverse effects* ; Middle Aged ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; Environmental Exposure/adverse effects* ; Life Style ; Aged ; Adult ; Risk Factors ; Cross-Over Studies ; East Asian People

AIM To screen the material basis for Rhei Radix et Rhizoma on improving human umbilical vein endothelial cell(HUVECs)injury before and after carbonization.METHODS The HPLC fingerprints were established,after which difference analysis was performed by orthogonal partial least squares discriminant analysis.The LPS-induced HUVECs injury model was established,then NO,MDA levels and SOD activity were detected.Gray correlation analysis and partial least squares regression were adopted in the investigation of spectrum-effect relationship,and active constituents were screened.RESULTS There were 22 and 20 common peaks in the fingerprints for 17 batches of raw products and carbonized products,respectively,along with the similarities of more than 0.8.Twelve main difference components were observable,among which gallic acid,5-hydroxymethylfurfural,catechin,aloe rhodopsin-8-O-β-D-glucoside,rhubarbic acid-8-O-β-D-glucoside and sennosides A were identified.The carbonized products demonstrated stronger effect on improving HUVECs injury than the raw product.The correlations of common peaks were more than 0.5 in the fingerprints for raw products and carbonized products,and peaks 3,5,11,12,15,19,23 exhibited significant effects on their efficacy(VIP values＞1).CONCLUSION This accurate,reliable and reproducible method can provide a basis for clarifying the material basis for hemostatic efficacy of Rhei Radix et Rhizoma and its carbonized product.

Objective:To evaluate the topological alterations of resting-state brain networks in patients with idiopathic generalized epilepsy with generalized tonic-clonic seizure (IGE-GTCS) using minimum spanning tree (MST) based on graph theoretic analysis, and to further analyze the relationships between topological features, duration, and antiepileptic drug response.Methods:This study was a cross-sectional study. Retrospectively, 75 IGE-GTCS patients and 37 healthy controls (HC) who underwent brain MR imaging at the Affiliated of Nanjing University Medical School Drum Tower Hospital from January 2013 to December 2020 were enrolled. IGE-GTCS patients were grouped into well-controlled subgroup (WC; n=55) and drug-resistant subgroup (DR; n=20) according to their response to antiepileptic drugs. Firstly, the time series correlations between 116 regions of the whole brain of each subject were calculated to construct functional connectivity matrices. For each functional connectivity matrix, the Kruskal algorithm was used to MST, and the topological metrics of each MST were calculated, including leaf fraction, tree hierarchy, and diameter. The comparison of MST topological metrics between the two groups was performed using two-sample t-test. Pearson correlation analysis was used to calculate the correlation between disease duration and MST metrics in the WC subgroup and the DR subgroup. Results:Compared with the HC group, the MST leaf fraction ( t=2.27, P=0.025) increased in the IGE-GTCS patient group, and the diameter decreased ( t=-2.24, P=0.027), there was no statistically significant difference in tree hierarchy between IGE-GTCS patient group and HC group ( t=0.98, P=0.328). The MST leaf fraction ( t=-2.39, P=0.019) and tree hierarchy ( t=-2.24, P=0.027) in the WC subgroup was decreased compared with the DR subgroup, while there was no statistically significant difference in diameter between WC subgroup and DR subgroup ( P=0.093). The correlation analysis showed the MST diameter in WC subgroup was significantly correlated with disease duration ( r=0.452, P<0.001), while the MST diameter in DR subgroup was not significantly correlated with disease duration ( r=-0.062, P=0.847). Conclusions:Patients with IGE-GTCS exhibit specific alterations in the global topology of brain network, characterized by increased centralization and efficiency. The effective antiepileptic drug treatment is associated with a recovery of brain network abnormalities.

Mild cognitive impairment due to Alzheimer′s disease is an inevitable pathological stage in the early development of Alzheimer′s disease, which can be classified as "microlumps in the brain collaterals" in traditional Chinese medicine. Based on the theory of latent toxin blocking collaterals, this article discusses the etiology and pathogenesis, clinical sequelae, and traditional Chinese medicine intervention strategies for mild cognitive impairment due to Alzheimer′s disease. The onset of mild cognitive impairment due to Alzheimer′s disease is very similar to the latent pathogen theory, which states that "the latent pathogen is latent and then develops, the poison is deep and difficult to cure, and the development can be recognized but the latent pathogen cannot be detected." Combining clinical experience, our team believes that the basic nature of the disease is a slight deficiency and a slight excess of symptoms. A slight deficiency of the five zang viscera and six fu viscera as root and a latent toxin colling collaterals of qi, fire, phlegm, and blood stasis as manifestaion. These usually start from the qi depression and develop into phlegm coagulation and blood stasis, then end up in latent toxin and gradually become the healthy qi deficiency. Therefore, the deficiency of vital qi and incubation of evil, latent toxin blocking collaterals the pathogenesis of early intervention of this disease should be carried out, upholding the idea that "the upper workman treats the disease before it is diagnosed." The principle of strengthening vital qi to eliminate pathogenic factors, slowing down and promoting pathogenic factors elimination, establishing the method of supporting correctness and wisdom, simultaneously detoxifying and clearing the blood stasis, pattern differentiation as the main and the disease differentiation as the first, combining the disease and pattern, and adjusting the macroscopic and microscopic, focusing simultaneously on eliminating and replenishing, dispel phlegm and remove blood stasis, achieve a strong vital qi and the elimination of evil, and enhance intelligence, delay or even block the progression of mild cognitive impairment due to Alzheimer′s disease, improve patients′ quality of life, and provide a theoretical basis for the early clinical prevention and treatment of Alzheimer′s disease.

Resistance to poly adenosine diphosphate(ADP)-ribose polymerase inhibitor(PARPi)presents a considerable obstacle in the treatment of ovarian cancer.F-box and tryptophan-aspartic(WD)repeat domain containing 11(FBXW11)modulates the ubiquitination of growth-and invasion-related factors in lung cancer,colorectal cancer,and osteosarcoma.The function of FBXW11 in PARPi therapy is still ambiguous.In this study,RNA sequencing(RNA-seq)showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi.FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer(HGSOC)tissues,and low levels of FBXW11 were associated with shorter overall survival(OS)and progression-free survival(PFS)in HGSOC patients.Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi,while knocking down FBXW11 made it less sensitive.The four-dimensional(4D)label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11(S100A11)and promoted its degradation through ubiquiti-nation.The increased degradation of S100A11 led to less efficient DNA damage repair,which in turn contributed to increased PARPi-induced DNA damage.The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models.In summary,our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S10OA11-mediated DNA damage repair.

Resistance to poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) presents a considerable obstacle in the treatment of ovarian cancer. F-box and tryptophan-aspartic (WD) repeat domain containing 11 (FBXW11) modulates the ubiquitination of growth-and invasion-related factors in lung cancer, colorectal cancer, and osteosarcoma. The function of FBXW11 in PARPi therapy is still ambiguous. In this study, RNA sequencing (RNA-seq) showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi. FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer (HGSOC) tissues, and low levels of FBXW11 were associated with shorter overall survival (OS) and progression-free survival (PFS) in HGSOC patients. Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi, while knocking down FBXW11 made it less sensitive. The four-dimensional (4D) label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11 (S100A11) and promoted its degradation through ubiquitination. The increased degradation of S100A11 led to less efficient DNA damage repair, which in turn contributed to increased PARPi-induced DNA damage. The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models. In summary, our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S100A11-mediated DNA damage repair.

Epitope vaccine is a novel strategy for vaccine development in recent years,exhibiting ad-vantages such as safety,and the ability to induce specific humoral and cellular immune responses a-gainst pathogens.Among them,the identification and delivery of epitopes are crucial in the design of multi-epitope vaccines.Compared to traditional methods of antigenic epitope identification,vari-ous new techniques such as bioinformatics,ELIspot,and intracellular cytokine staining have been developed.Since the direct immunization of multi-epitope peptides results in low protective effica-cy,efficient delivery systems are urgently needed.The antigenic epitopes commonly used delivery systems include viral vectors,and non-virus vectors such as nanoparticles,etc.Additionally,to en-hance the immunization efficacy of vaccines,antigenic epitopes are usually modified,including mul-tiple epitopes in tandem and epitope targeting modification and other strategies.This review sum-marizes the methods for accurate identification of antigenic epitopes with well immunogenicity as well as effective delivery strategies for antigenic epitopes,providing new insight into the develop-ment of novel multi-epitope vaccines.

Objective:To investigate the effects of ascites grading and the application of non-selective beta-blockers (NSBBs) on the 1-year prognosis of acute-on-chronic liver failure (ACLF).Methods:1 386 ascitic cases with ACLF were graded and followed up for one year. The 1-year prognostic effect of ascites grade and NSBBs was analyzed on ACLF by the Kaplan Meier Log-rank test, Cox stepwise regression, and multivariate regression.The t-test, Mann-Whitney U, or Kruskal-Wallis test were used for intergroup comparison of measurement data. The χ2 test was used for intergroup comparison of numerical data. Results:The incidence rate of ascites at admission was 77.56% in 1 386 ACLF cases. The Log-rank (Mantel-Cox) of the 1-year survival curve test for 1 386 ACLF patients with ascites grade was 21.384, P<0.01. Multivariate regression and Cox stepwise regression analysis showed that ascites grade, age, gastrointestinal bleeding, pulmonary infection, acute kidney injury, prothrombin activity (PTA), urea, MELD-Na score, and the use of NSBBs were closely related to the 1-year prognosis of ACLF. The log rank (Mantel-Cox) of NSBBs treatment in the grade 2/3 ascites group was 6.113, P=0.013, and the difference was statistically significant, suggesting that NSBBs treatment can help improve the 1-year survival rate in ACLF patients with grade 2 and 3 ascites. Conclusions:Ascites grading and the use of NSBBs affect the prognostic factor of ACLF at one year. NSBBs may be beneficial for the long-term prognosis of ACLF, and treatment can be continued in patients who have already received NSBBs prior to the onset of ACLF.