Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.

With the emergence of deep learning techniques based on convolutional neural networks, artificial intelligence (AI) has driven transformative developments in the field of medical image analysis. Recently, large language models (LLMs) such as ChatGPT have also started to achieve distinction in this domain. Increasing research shows the undeniable role of AI in reshaping various aspects of medical image analysis, including processes such as image enhancement, segmentation, detection in image preprocessing, and postprocessing related to medical diagnosis and prognosis in clinical settings. However, despite the significant progress in AI research, studies investigating the recent advances in AI technology in the aforementioned aspects, the changes in research hotspot trajectories, and the performance of studies in addressing key clinical challenges in this field are limited. This article provides an overview of recent advances in AI for medical image analysis and discusses the methodological profiles, advantages, disadvantages, and future trends of AI technologies.
Artificial Intelligence ; Humans ; Image Processing, Computer-Assisted/methods* ; Neural Networks, Computer ; Deep Learning ; Diagnostic Imaging/methods*

Objective:To investigate the value of MULTI-parametric MR imaging with flexible design (MTP) combined with microview diffusion weighted imaging (DWI) in predicting pituitary tumor invasion of cavernous sinus.Methods:This was a cross-sectional study. The clinicopathological and imaging data of 59 patients with suspected pituitary tumor who were admitted to the First Affiliated Hospital of Dalian Medical University from December 2021 to August 2024 were prospectively analyzed. According to Knosp classification, patients with pituitary tumor were divided into non-invasive group (28 cases) and invasive group (31 cases). All patients underwent MTP and microview DWI sequence scanning, and the corresponding parameter values [T 1, R 2*, T 2* and apparent diffusion coefficient (ADC)] were measured on the MTP quantitative map and ADC map at the maximum diameter level of the pituitary tumor. Independent sample t test and Mann-Whitney U test were used to compare the clinical data, quantitative parameter values and proliferation index (Ki-67) between the non-invasive group and the invasive group. Quantitative parameter values with statistically significant differences were jointly included in logistic regression to construct the model. Receiver characteristic curve and area under the curve (AUC) were used to analyze single variables and logistic model in predicting the value invasion of pituitary tumor cavernous sinus invasion. Spearman correlation was used to analyze the correlation between the quantitative values and Ki-67 level. Results:There was no significant difference in age and gender between the non-invasive group and the invasive group ( P>0.05). T 1 and T 2* values in invasion group were higher than those in non-invasion group ( Z=4.42, P<0.001; Z=3.43, P<0.001), R 2* values and ADC values in the invasion group were lower than those in the non-invasion group, and the difference was statistically significant (t=4.07, P<0.001; Z=-3.07, P=0.002). The AUC values of T 1, R 2*, T 2*, ADC, logistic model 1(T 1+R 2*+ADC) and logistic model 2(T 1+T 2*+ADC) for predicting pituitary tumor cavernous sinus invasion were 0.835, 0.767, 0.760, 0.733, 0.926 and 0.925, respectively. Correlation analysis showed that the value of pituitary tumor T 1 was positively correlated with Ki-67 ( r=0.431, P=0.002). Conclusion:Quantitative parameters of MTP sequence and microview DWI sequence can quantitatively evaluate pituitary tumor invasion of cavernous sinus, and the combination of the two sequences can significantly improve the prediction efficiency.

Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.

Objective:To investigate the value of MULTI-parametric MR imaging with flexible design (MTP) combined with microview diffusion weighted imaging (DWI) in predicting pituitary tumor invasion of cavernous sinus.Methods:This was a cross-sectional study. The clinicopathological and imaging data of 59 patients with suspected pituitary tumor who were admitted to the First Affiliated Hospital of Dalian Medical University from December 2021 to August 2024 were prospectively analyzed. According to Knosp classification, patients with pituitary tumor were divided into non-invasive group (28 cases) and invasive group (31 cases). All patients underwent MTP and microview DWI sequence scanning, and the corresponding parameter values [T 1, R 2*, T 2* and apparent diffusion coefficient (ADC)] were measured on the MTP quantitative map and ADC map at the maximum diameter level of the pituitary tumor. Independent sample t test and Mann-Whitney U test were used to compare the clinical data, quantitative parameter values and proliferation index (Ki-67) between the non-invasive group and the invasive group. Quantitative parameter values with statistically significant differences were jointly included in logistic regression to construct the model. Receiver characteristic curve and area under the curve (AUC) were used to analyze single variables and logistic model in predicting the value invasion of pituitary tumor cavernous sinus invasion. Spearman correlation was used to analyze the correlation between the quantitative values and Ki-67 level. Results:There was no significant difference in age and gender between the non-invasive group and the invasive group ( P>0.05). T 1 and T 2* values in invasion group were higher than those in non-invasion group ( Z=4.42, P<0.001; Z=3.43, P<0.001), R 2* values and ADC values in the invasion group were lower than those in the non-invasion group, and the difference was statistically significant (t=4.07, P<0.001; Z=-3.07, P=0.002). The AUC values of T 1, R 2*, T 2*, ADC, logistic model 1(T 1+R 2*+ADC) and logistic model 2(T 1+T 2*+ADC) for predicting pituitary tumor cavernous sinus invasion were 0.835, 0.767, 0.760, 0.733, 0.926 and 0.925, respectively. Correlation analysis showed that the value of pituitary tumor T 1 was positively correlated with Ki-67 ( r=0.431, P=0.002). Conclusion:Quantitative parameters of MTP sequence and microview DWI sequence can quantitatively evaluate pituitary tumor invasion of cavernous sinus, and the combination of the two sequences can significantly improve the prediction efficiency.

Objective With the widespread of transcatheter aortic valve replacement(TAVR)in patients with severe symptomatic aortic stenosis(AS),the life-cycle management has become a major determinant of prognosis.Methods A total of 408 AS patients who underwent successfully TAVR from June 2021 to August 2023 were consecutively enrolled in Hospital Valve Intervention Center.Patients were assigned to the Usual Care(UC)group between June 2021 and October 2022,while patients were assigned to the Heart Multi-parameter Monitoring(HMM)group between November 2022 and August 2023.The primary endpoint was defined as composite endpoint within 6 months post-TAVR,including all-cause death,cardiovascular death,stroke/transient ischemic attack,conduction block,myocardial infarction,heart failure rehospitalization,and major bleeding events.Secondary endpoints were the time interval(in hours)from event occurrence to medical consultation or advice and patient satisfaction.Statistical analysis was performed using Kaplan-Meier and multivariable Cox proportional hazards models.Results The incidence of primary endpoint in HMM group was significantly lower than that in UC group(8.9％vs.17.7％,P=0.016),the driving event was the rate of diagnosis and recognition of conduction block.The average time intervals from event occurrence to receiving medical advice were 3.02 h in HHM group vs.97.09 h in UC group(P＜0.001).Using cardiac monitoring devices and smart healthcare platforms provided significant improving in patients long-term management(HR 0.439,95％CI 0.244-0.790,P=0.006).Conclusions The utilization of cardiac monitoring devices and smart healthcare platforms effectively alerted clinical events and improved postoperative quality of life during long-term management post TAVR.

AIM To optimize the extraction process for uracil,hypoxanthine,xanthine,uridine,thymine,inosine,guanosine and 2'-deoxyguanosine from Pheretima guillelmi(Michaelsen),and to determine their contents.METHODS With solid-liquid ratio,ultrasonic time and ultrasonic temperature as influencing factors,contents of hypoxanthine and total nucleosides as evaluation indices,the extraction process was optimized by orthogonal test.HPLC was adopted in the content determination of varioud nucleosides,the analysis was performed on a 30℃thermostatic Agilent C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of methanol-water flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 260 nm.RESULTS The optimal conditions were determined to be 1∶250 for solid-liquid ratio,60 min for ultrasonic time,and 60℃for ultrasonic temperature.Eight nucleosides showed good linear relationships within their own ranges(R2＞0.999 0),whose average recoveries were 99.11%-103.27%with the RSDs of 0.85%-2.89%.CONCLUSION This stable and reliable method can be used for the extraction and content determination of nucleosides from P.guillelmi.

Objective:To explore the causes of the crosstalk in the gross α and gross β measurement using an MPC 9604 low background α/β counter.Methods:With the A4 copy paper (70 g/m 2), polyethylene (PE) films (8.7 g/m 2), and 304 stainless steel seperately as shielding materials, the gross α and gross β experiments, gamma spectrometry experiments and solid state nuclear track detection (SSNTD) experiments were conducted by using 241Am and 40K standard materials. A comprehensive analysis encompassing statistical analysis and nuclear physics analysis was performed to reveal the impact of contributing factors on the crosstalk in the gross α and gross β measurement with an MPC 9604 low background α/β counter. Results:241Am powder source experimental result: when two sheets of copy paper were used in the experiment, α-rays did not generate one count in the β channel of the low background α/β counter. The same test with the shielding material of two layers of PE films showed that the α count rate further decreased by about 36.5%, while the β count rate hardly changed. The gross α and gross β experiments and γ spectrometry with the shielding material of stainless steel demonstrated that the characteristic γ ray peaking at 59.5 keV of the 241Am powder source did not generate one count in the β channel. 40K powder source experimental result: when the source was covered with steel of total thickness of 0.965 mm in the gross α and gross β experiments, the γ rays of 40K did not generate one count in the β channel. Compared with naked 40K powder source, when source was covered with one and two sheets of copy paper, the gross α count rate decreased approximately from 3.30 × 10 -3 to 1.50 × 10 -3 and 1.75 × 10 -3, respectively. The SSNTD indicated the presence of other α nuclides in 40K powder source. Conclusions:The β counting in the β channel with the 241Am powder source using MPC 9604 low background α/β counter was, instead of α-rays, caused by the internal conversion electrons and the characteristic X rays of 11.870-22.402 keV emitted from the 241Am powder source, thus this is not a true α/β crosstalk. The α counting in α channel with the 40K powder source, except the contribution of impurity α nuclides, was mainly attributed to the α signals arising from β particles when the amplitude of the piled-up β pules exceeded the discrimination threshold of the detector, therefore it is a true crosstalk.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*

Ischemic stroke(IS)is the main cause of neurological dysfunction in adults in China,and rapid,timely,and accurate prediction of post-stroke outcome and intervention treatment are crucial.Currently,the prognosis of ischemic stroke mainly relies on neuroimaging and clinical assessment,and there is still a lack of objective and simple rapid prediction tools.Recent studies have shown that early measurement of peripheral blood-derived biomarkers may be able to predict stroke patient outcomes,thereby optimizing stroke management,improving patient rehabilitation,and improving stroke outcomes.This article reviews the progress of studies on the correlation between peripheral blood biomarkers and clinical prognosis of ischemic stroke.