Advancements in artificial intelligence (AI) and emerging technologies are rapidly expanding the exploration of chemical space, facilitating innovative drug discovery. However, the transformation of novel compounds into safe and effective drugs remains a lengthy, high-risk, and costly process. Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development. Despite this need, no comprehensive tool currently supports systematic evaluation and efficient screening. Here, we present druglikeFilter, a deep learning-based framework designed to assess drug-likeness across four critical dimensions: 1) physicochemical rule evaluated by systematic determination, 2) toxicity alert investigated from multiple perspectives, 3) binding affinity measured by dual-path analysis, and 4) compound synthesizability assessed by retro-route prediction. By enabling automated, multidimensional filtering of compound libraries, druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates, which can be freely accessed at https://idrblab.org/drugfilter/.

Objective:To explore the value of the vesical imaging-reporting and data system (VI-RADS) score based on multiparametric MRI (mpMRI) combined with quantitative tumor MRI parameters in assessing the muscle invasion of bladder cancer.Methods:The study was a case-control study. The data of 87 bladder cancer patients confirmed by pathology who underwent mpMRI of the bladder were retrospectively collected from the First Medical Center of Chinese PLA General Hospital between January 2019 and April 2023 The pathological findings were used as the gold standard to categorize them into the muscle invasive bladder cancer (MIBC) group (29 cases) and non-muscle invasive bladder cancer (NMIBC) group (58 cases). Quantitative parameters were measured based on preoperative mpMRI images, including the length of tumor bladder wall contact, the perpendicular distance between the bladder tumor and the tangent of the bladder wall, the maximal diameter of the bladder tumor, and the volume of the bladder tumor. Bladder cancer was classified according to the VI-RADS scoring criteria. The Mann-Whitney U test was used for intergroup comparisons. Multivariate logistic regression analysis was performed to obtain the independent risk factors related to muscle invasion of bladder cancer and to establish the model. The receiver operating characteristic curves were analyzed for MRI quantitative parameters and logistic regression models, and area under the curve (AUC) comparisons were performed using the DeLong test. Results:The differences in tumor bladder wall contact length, perpendicular distance from the tumor to the tangent line of the bladder wall, maximum diameter, bladder tumor volume, and the VI-RADS scores were statistically significant between the MIBC group and the NMIBC group ( P<0.05). Multifactorial logistic regression analysis showed that tumor bladder wall contact length ( OR=21.07, 95% CI 3.56-124.89, P=0.001) and VI-RADS score ( OR=11.90, 95% CI 3.53-40.12, P<0.001) were the independent risk factors for evaluating the muscle invasion of bladder cancer. The difference between the VI-RADS score and the tumor bladder wall contact length for assessing muscular infiltration of bladder cancer had AUCs of 0.802 (95% CI 0.704-0.899) and 0.759 (95% CI 0.652-0.865). The combined model of VI-RADS score combined with tumor bladder wall contact length had an AUC of 0.891 (95% CI 0.812-0.970), which was higher than the diagnostic efficacy of applying tumor bladder wall contact length or VI-RADS score alone ( Z=3.05, 2.37, P=0.002, 0.018). Conclusion:Tumor contact length with the bladder wall is an independent risk factor for assessing muscle invasion of bladder cancer and the combination of VI-RADS score may enhances diagnostic accuracy.

Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.

Objective:To observe the effect of electroacupuncture at the Shuigou point on systolic phenotype-related factors and on the JAK1/STAT3 signaling pathway of the middle cerebral artery smooth muscle cells in rats modeling cerebral infarction; and to explore the molecular mechanism of treating cerebral infarction with electroacupuncture.Methods:A total of 108 healthy male Wistar rats were randomly divided into a blank group ( n=6), a sham operation group ( n=6), a model group ( n=48) and an electroacupuncture group ( n=48). The model and electroacupuncture groups were randomly divided into eight phase subgroups at 1h, 3h, 6h, 12h, 24h, 72h, 7d and 14d after the modeling of middle cerebral artery occlusion (MCAO), with six rats in each group. The electroacupuncture groups received electric acupuncture at the Shuigou acupoint for 20min after successful modeling. Neurological Severity scoring (NSS) was used to evaluate the neurological impairment. PLN protein expression in the middle cerebral artery and the expression of JAK1 and STAT3 proteins in the rats′ brain tissue were detected using western blotting. PDGF-AA content in the middle cerebral artery was measured using enzyme-linked immunosorbent assays. Results:Compared with the blank and sham operation groups, the average NSS score and PDGF-AA protein expression had increased significantly in the model and electroacupuncture groups. PLN protein expression had decreased significantly at 12h-14d in the model group, but decreased significantly at 12h-7d in the electroacupuncture group. Compared with those two groups, there was a significant increase in JAK1 protein expression at 1h-72h, 3h-6h, 24h-72h, and14d in the model group. In the electroacupuncture group the corresponding significant increases were over 1h-14d, 1h-6h, 24h, 72h, and 14d. STAT3 protein expression had increased significantly in the model group over 6h-14d and 3h-14d. In the electroacupuncture group those increases were over 6h-14d. Compared to the model group, a significant increase was observed in the expression of PLN protein at 14d, with a significant decrease in NSS at 72h, 7d and 14d. PDGF-AA protein had increased significantly at 6h-7d. For JAK1 protein that was at 12h and 14d, and for STAT3 protein it was over 12h-72h and at 14d.Conclusion:Electroacupuncture at the Shuigou point may regulate the expression of PDGF-AA and the JAK/STAT signaling pathway so as to regulate the normal expression of PLN, and thus smooth muscle contraction to maintain the normal functioning of the middle cerebral artery. This may be one of the molecular mechanisms by which electroacupuncture at the Shuohui point improves nerve functioning in treating cerebral infarction.

Objective:To compare the clinical manifestations,laboratory results,and imaging features between pyogenic spondylitis(PS) and tuberculous spondylitis(TS).Methods:This was a cross-sectional study. A total of 88 patients with infectious diseases of spine(IDS) admitted to Shanghai Sixth People′s Hospital from January 2021 to December 2023 were analyzed,including 61 PS cases(PS group) and 27 TS cases(TS group). The clinical manifestations,laboratory results,and imaging features were compared between two groups. The factors associated with PS were analyzed by multivariate logistic regression. The diagnostic efficacy for pathogen identification was compared between metagenomics next-generation sequencing(mNGS) and bacterial culture methods in PS and TS patients.Results:Compared with the TS group,the PS group had a higher age-adjusted Charlson comorbidity index(aCCI)[3.0(1.5,4.0) points vs. 2.0(1.0,3.0) points, Z=-2.189, P=0.029],shorter onset time of disease[1.0(0.8,3.0) months vs. 6.0(2.0,12.0) months,Z=-4.353, P<0.001],and higher median blood leukocyte counts and serum ferritin(SF) level(7.2×10 9/L vs. 6.3×10 9/L, Z=-2.652, P=0.008; 571.3 ng/ml vs. 266.0 ng/ml, Z=-4.773, P<0.001). The proportions of lumbar spine involvement,non-collapsed involved vertebrae,and bone bridges formed were all higher in the PS group compared to the TS group[68.8%(99/144) vs. 41.4%(29/70), χ2=14.628, P<0.001; 68.9%(42/61) vs. 18.5%(5/27), χ2=19.055, P<0.001; 41.0%(25/61) vs. 7.4%(2/27), χ2=9.921, P=0.002]. The proportions of thoracic spine involvement,severe vertebral collapse,severe narrowing of the involved intervertebral space,sequestrum,and paravertebral soft tissue calcification were all higher in the TS group compared to the PS group[52.9%(37/70) vs. 18.1%(26/144), χ2=27.463, P<0.001; 55.6%(15/27) vs. 13.1%(8/61), χ2=17.462, P<0.001; 74.1%(20/27) vs. 37.7%(23/61), χ2=9.907, P=0.002; 74.1%(20/27) vs. 18.0%(11/61), χ2=25.761, P<0.001; 51.9%(14/27) vs. 6.6%(4/61), χ2=23.599, P<0.001]. Multivariate logistic regression analysis indicated that a symptom duration<5.5 months( OR=30.644,95% CI: 2.022-464.529, P<0.05) and a leukocyte count>7.35×10 9/L( OR=48.653,95% CI: 2.045-1 157.721, P<0.05) indicated a higher likelihood of PS; while the vertebral collapse indicated a higher likelihood of TS( OR=0.025,95% CI: 0.001-0.638, P<0.05). The most common pathogen in the PS group was Staphylococcus aureus(31 cases,50.8%),followed by Streptococcus species(10 cases,16.4%). The positive rates of mNGS testing in the PS and TS groups were 84.1%(37/44) and 12/13,respectively,which were higher than those of conventional bacterial culture[77.8%(42/54)] and Mycobacteriumtuberculosis culture(2/11). Conclusions:Compared with the TS patients,the PS patients have shorter onset time,higher aCCI scores,higher blood leukocyte counts and SF levels,less vertebral collapse and intervertebral space narrowing,and more bone bridge formation. The TS patients have more dead bones and calcifications. The mNGS has a higher diagnostic efficacy than bacterial cultures for PS and TS.

Advancements in artificial intelligence(AI)and emerging technologies are rapidly expanding the exploration of chemical space,facilitating innovative drug discovery.However,the transformation of novel compounds into safe and effective drugs remains a lengthy,high-risk,and costly process.Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development.Despite this need,no comprehensive tool currently supports systematic evaluation and efficient screening.Here,we present druglikeFilter,a deep learning-based framework designed to assess drug-likeness across four critical dimensions:1)physicochemical rule evaluated by systematic determination,2)toxicity alert investigated from multiple perspectives,3)binding affinity measured by dual-path analysis,and 4)compound synthesizability assessed by retro-route prediction.By enabling automated,multidimensional filtering of compound libraries,druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates,which can be freely accessed at https://idrblab.org/drugfilter/.

Objective:To evaluate the safety and efficacy of accelerator-based boron neutron capture therapy (AB-BNCT) in the treatment of recurrent and refractory malignant tumors.Methods:The data of 14 patients admitted to Xiamen Humanity Hospital from September 2022 to April 2023 were prospectively collected, including 7 patients with primary brain malignancies and 7 patients with locally recurrent inoperable head and neck malignancies. All patients received intravenous infusion of boron drug (NBB-001, p-dihydroxyborylphe nylalanine, a patented freeze-dried formulation) at a total nominal dosage of 500 mg/kg (11 patients) or 750 mg/kg (3 patients), and were irradiated with neutrons (operating with NeuPex system). Adverse events after treatment were recorded and assessed. The primary efficacy endpoint was the 90 d objective response rate (ORR), while the secondary endpoints included progression-free survival (PFS) and complete response rate (CRR). Data were compiled and analyzed by SAS 9.4 software. The rate and 95% CI were calculated using Clopper-Pearson method. Results:The median dose delivered to 80% of the target volume (D 80%) was 16.80 GyE (range: 8.93-23.79 GyE). The most common adverse reactions were hyperamylasemia, alopecia, and hyperprolactinemia. Five patients experienced 8 cases of grade 3 or above adverse events, including 1 case of grade 4 acute kidney injury and 7 cases of grade 3 adverse events. All adverse events were recovered after observation or treatment. At 90 d after treatment, the ORR of all patients was 9/14 (64%, 95% CI: 35%-87%), disease control rate (DCR) was 10/14 (71%, 95% CI: 42%-92%), CRR was 2/14 (14%, 95% CI: 2%-42%); and the best overall response during the entire course included an ORR of 10/14 (71% ,95% CI: 42%-92%), DCR of 13/14 (93%, 95% CI: 66%-100%), and CRR of 3/14 (21% ,95% CI: 5%-51%). The 1-year survival rate for head and neck malignancies was 71.4%, and the 2-year survival rate was 42.8%. The 1-year survival rate for recurrent brain malignancies was 42.8%. Conclusion:AB-BNCT demonstrates favorable safety and promising efficacy in treating primary brain malignancies and recurrent/refractory head and neck malignancies, representing a potential therapeutic option.

AIM:To identify the expression characteristics of transfer RNA-derived small RNAs(tsRNAs)re-sponding to DNA damage in human hepatoblastoma HepG2 cells,and to investigate their potential functions.METHODS:Based on paired HepG2 cells and TP53 gene knockout HepG2 cells,we successfully constructed a DNA damage cellular model using adriamycin(ADR).Transcriptome analysis of small noncoding RNAs was performed to systematically identi-fy a set of tsRNAs responding to ADR and involved in p53 regulation.Functional enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes(KEGG).Additionally,after silencing the expression of target tsRNA genes,the biological functions of these tsRNAs in HepG2 cells were initially confirmed through CCK-8 assay and plate colo-ny formation assay.RESULTS:DNA damage induced a set of tsRNAs involved in p53 regulation,among which tRF-5-1(tRF-5_tRNA-Gly-TCC-2-1)and tRF-i-1(tRF i_tRNA-Tyr-GTA-11-1)showed the most significant up-regulation in HepG2 cells(P<0.05).Silencing of either tRF-5-1 or tRF-i-1 gene inhibited the proliferative activity of HepG2 cells(P<0.05).CONCLUSION:A group of tsRNAs responding to DNA damage can be identified in HepG2 cell model,and tsRNAs can promote the proliferative activity of HepG2 cells,suggesting that tsRNAs may play an important role in the de-velopment and progression of liver malignancies.

Objective To explore the microstructural alterations in the white matter of patients with Parkinson's disease(PD)with depression(PD-D)by Tract-based Spatial Statistics(TBSS),with the aim of identifying neuroimaging biomarkers for early diagnosis.Methods Participants with PD were recruited from the Parkinson Progression Marker Initiative database and categorized into PD-D group(n=50)and PD without depression(PD-ND)group(n=31)based on the Geriatric Depression Scale(GDS-15).Age-and gender-matched healthy volunteers were also included in healthy control(HC)group(n=23).All subjects underwent brain MRI-DTI scans.TBSS was utilized to compare fractional anisotropy(FA),mean diffusivity(MD),axial diffusivity(AD),and radial diffusivity(RD)values among groups and to perform Pearson correlation analysis with clinical PD data.Results Compared with HC group,FA values were significantly reduced and MD values were significantly increased in bilateral cingulate(hippocampus),crus,parahippocampal,inferior fronto-occipital fasciculus,inferior longitudinal fasciculus,uncinate fasciculus,superior longitudinal fasciculus(SLF),SLF(temporal),thalamic radiation and corticospinal tract of PD-D group(all P＜0.05).Compared with PD-ND group,MD values were significantly higher in the left cingulum(cingulate gyrus),left inferior fronto-occipital fasciculus,left SLF,left SLF(temporal),left thalamic radiation and left corticospinal tract of PD-D group,while AD values were significantly higher in the left SLF of PD-D group(all P＜0.05).Correlation analysis revealed that AD values in the left SLF were positively correlated with Epworth sleepiness scale score and GDS-15 score(r=0.192,P=0.043;r=0.443,P＜0.01).MD values in the differential brain regions were negatively correlated with Montreal cognitive assessment scale scores(r=-0.187,P=0.047)and positively correlated with GDS-15 scores(r=0.485,P＜0.01).Conclusion This study demonstrate that TBSS can reveal microstructural changes in the brains of PD-D patients,which may serve as neuroimaging biomarkers and provide guidance for clinical diagnosis and treatment.

Objective To explore the microstructural alterations in the white matter of patients with Parkinson's disease(PD)with depression(PD-D)by Tract-based Spatial Statistics(TBSS),with the aim of identifying neuroimaging biomarkers for early diagnosis.Methods Participants with PD were recruited from the Parkinson Progression Marker Initiative database and categorized into PD-D group(n=50)and PD without depression(PD-ND)group(n=31)based on the Geriatric Depression Scale(GDS-15).Age-and gender-matched healthy volunteers were also included in healthy control(HC)group(n=23).All subjects underwent brain MRI-DTI scans.TBSS was utilized to compare fractional anisotropy(FA),mean diffusivity(MD),axial diffusivity(AD),and radial diffusivity(RD)values among groups and to perform Pearson correlation analysis with clinical PD data.Results Compared with HC group,FA values were significantly reduced and MD values were significantly increased in bilateral cingulate(hippocampus),crus,parahippocampal,inferior fronto-occipital fasciculus,inferior longitudinal fasciculus,uncinate fasciculus,superior longitudinal fasciculus(SLF),SLF(temporal),thalamic radiation and corticospinal tract of PD-D group(all P＜0.05).Compared with PD-ND group,MD values were significantly higher in the left cingulum(cingulate gyrus),left inferior fronto-occipital fasciculus,left SLF,left SLF(temporal),left thalamic radiation and left corticospinal tract of PD-D group,while AD values were significantly higher in the left SLF of PD-D group(all P＜0.05).Correlation analysis revealed that AD values in the left SLF were positively correlated with Epworth sleepiness scale score and GDS-15 score(r=0.192,P=0.043;r=0.443,P＜0.01).MD values in the differential brain regions were negatively correlated with Montreal cognitive assessment scale scores(r=-0.187,P=0.047)and positively correlated with GDS-15 scores(r=0.485,P＜0.01).Conclusion This study demonstrate that TBSS can reveal microstructural changes in the brains of PD-D patients,which may serve as neuroimaging biomarkers and provide guidance for clinical diagnosis and treatment.