Objective:To investigate the value of coronary CTA (CCTA)-based traditional features and radiomics of plaque in the identification of culprit lesions that caused acute myocardial infarction (AMI).Methods:This was a retrospective multicenter study. From July 2016 to November 2023, a total of 344 patients from the Affiliated Hospital of Qingdao University (training cohort, n=184), Shandong Provincial Hospital Affiliated to Shandong First Medical University (validation cohort, n=88) and Qilu Hospital of Shandong University (test cohort, n=72) who received percutaneous coronary intervention (PCI) due to AMI and underwent CCTA within 48 hours of AMI were enrolled. The culprit plaques and non-culprit plaques were identified using a combination of electrocardiogram, CCTA, and angiographic findings. The vessel, plaque location, plaque type, Coronary Artery Disease-Reporting and Data System (CAD-RADS) score, high-risk plaque characteristics, plaque length, plaque volume, and burden were analyzed, and 1 904 radiomics features were extracted for each plaque. The traditional imaging model, the radiomics model, and the combined model were established by using multivariate Logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of each model in identifying culprit lesions. The DeLong test was used for the comparison of AUC between every two models. The net reclassification index (NRI) was used to evaluate the incremental value of the combined model to the traditional imaging model and the radiomics model. The decision curve analysis (DCA) was used to assess the clinical net benefit of these models. A correlation heatmap was used to evaluate the correlation between the radiomics score and traditional CCTA factors. The interpretable analysis of the decision process of the combined model was performed by the Shapley Additive exPlanations (SHAP). Results:In the validation cohort and the test cohort, the AUC of the traditional imaging model developed by the vessel, plaque type, positive remodeling and CAD-RADS score was 0.898 (95% CI 0.869-0.922) and 0.881 (95% CI 0.848-0.910), respectively. The radiomics model developed by six radiomics features was 0.863 (95% CI 0.831-0.891) and 0.863 (95% CI 0.827-0.864), respectively. The AUC of the combined model was 0.930 (95% CI 0.905-0.950)and 0.919 (95% CI 0.889-0.942), respectively. In the validation cohort and the test cohort, the AUC of the combined model was higher than that of the traditional imaging model ( Z=4.013, 4.272, P<0.001) and that of the radiomics model ( Z=4.819, 3.784, P<0.001), respectively. In the validation cohort, the combined model yielded an NRI of 20.43% (95% CI 10.43%-30.44%, P<0.001) and 20.21% (95% CI 9.62%-30.80%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. In the test cohort, the combined model yielded an NRI of 28.05% (95% CI 16.72%-39.38%, P<0.001) and 23.57% (95% CI 13.58%-33.56%, P<0.001) for identifying culprit lesions compared with the traditional imaging model and the radiomics model, respectively. DCA showed the combined model had the highest clinical net benefit. The correlation heatmap showed the radiomics score was not correlated or only weakly correlated with traditional CCTA factors. SHAP indicated the radiomics and CAD-RADS score contributed significantly to the model. Conclusion:The CCTA-based traditional features and radiomics of plaque have favorable performance for the identification of culprit plaques in patients with AMI.

[Purpose]To analyze the incidence,mortality and disease burden of malignant tumors in the cancer registration areas of Hebei Province in 2020.[Methods]The incidence and mortality data of cancer in 2020 were collected from the cancer registries of Hebei Province,and the quality of data was evaluated.The crude incidence(mortality)rate,age-specific incidence(mortality)rates and age-standardized incidence(mortality)rates by Chinese standard population(ASIRC/ASMRC)and world standard population(ASIRW/ASMRW)were calculated and analyzed.The disability-ad-justed life years(DALY)were calculated and analyzed according to the Excel disease burden cal-culation template recommended by the World Health Organization(WHO).[Results]In 2020,the crude incidence rate,ASIRC,ASIRW of malignant tumors in the cancer registration areas of Hebei Province were 229.36/105,147.06/105 and 143.74/105,respectively.The incidence rate in men was higher than that in women.The incidence rates in urban and rural areas were 230.26/105 and 228.84/105,and the age-standardized incidence rates reached a peak in the age group of 80～84 years old.The crude mortality rate,ASMRC,ASMRW were 146.38/105,85.33/105 and 84.79/105,respectively.The mortality rate in men was higher than that in women.The age-standardized mor-tality rate rose with age,reaching a peak in the age group of 85+years old,and the crude mortality rates in urban and rural areas were 143.82/105 and 147.84/105,respectively.The DALY of ma-lignant tumors in the cancer registration areas of Hebei Province were 345 030 person-years,reaching a maximum in the age group of 45～59 years old,with a DALY rate of 15.00/103,and the highest in the age group of 70～79 years old.Lung cancer had the heaviest disease burden,with DALY of 83 684 person-years,accounting for 24.25％of all malignant tumors,followed by stomach,liver,female breast,and colorectal cancers.The DALY in urban and rural areas were 122 062 and 222 993 person-years,respectively,and the trends in DALY rates were basically stable.[Conclusion]The disease burden of malignant tumors in Hebei Province is relatively heavy,cancer prevention and control should be further strengthened and focused on urban men and the elderly to reduce disease burden of malignant tumors in the future.

AIM:To investigate the modulatory role of E3 ubiquitin-protein ligase ITCH in Alzheimer disease(AD)-like pathology through the thioredoxin-interacting protein(TXNIP)-nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)signaling pathway using both in vivo and in vitro experimental models.METHODS:(1)Ten 5×FAD(AD model)mice and 10 wild-type(WT)mice at 2-,4-and 6-month-old were randomly allocated into AD and WT groups.Amyloid β-protein(Aβ)plaque burden in the brain was detected by thioflavin-S and immunofluorescence staining,with the latter method additionally applied to assess TXNIP protein expression.The protein levels of ITCH and TXNIP were determined by Western blot,while their interaction was verified by co-immunoprecipitation.(2)Mouse mi-croglia BV2 cells stimulated by lipopolysaccharide(LPS)were used to construct neuroinflammation model,and were di-vided into control(CON)group and LPS+ATP treatment group.The BV2 cells stimulated by Aβ were used to construct AD inflammation model.According to the different treatment time,they were divided into CON,and 12,24 and 48 h treatment groups.Western blot was used to evaluate the expression of ITCH,TXNIP,and NLRP3 inflammasome compo-nents(NLRP3 and caspase-1)as well as the downstream IL-1β.Adenovirus-mediated ITCH overexpression(OE-ITCH)in Aβ-stimulated BV2 cells comprised three experimental groups:negative control group,Aβ oligomer stimulation group,and OE-ITCH group,with subsequent immunoblotting of inflammatory mediators.RESULTS:The deposition of Aβ plaques in the cortex and hippocampus of 5×FAD transgenic mice exhibited an age-dependent progression(P<0.01).Compared with WT mice,the levels of TXNIP protein increased synchronously,and the levels of ubiquitin ligase ITCH was significantly down-regulated(P<0.05).Co-immunoprecipitation confirmed the interaction between ITCH and TXNIP proteins in the brain of 2-and 4-month-old 5×FAD mice,which exhibited marked attenuation by 4 months of age.In BV2 microglial models,Aβ/LPS stimulation provoked significant ITCH suppression,concurrently up-regulating TXNIP,core NLRP3 inflammasome components(NLRP3 and caspase-1),and downstream IL-1β(P<0.05).Overexpression of ITCH significantly inhibited Aβ-induced activation of TXNIP and NLRP3 and therelated inflammatory factors in BV2 cells.CONCLUSION:The results of in vitro and in vivo experiments showed that ITCH protein exerts effects against AD-like pathology by inhibiting the expression of TXNIP-NLRP3 signaling pathway.

Objective:With the aggravation of population aging, the burden of malignant tumors in the elderly population is becoming more and more heavy. This study aims to analyze the incidence and mortality of malignant tumors in the elderly population in Hebei Province in the past decade.Methods:The incidence and mortality data of malignant tumors in people aged ≥60 years old in 38 cancer registration areas in Hebei Province from 2011 to 2020 were collected, and the incidence and mortality were analyzed by gender, urban and rural areas, and age groups. The age standardized rates were calculated using the 2000 Chinese population census and Segi′s world population. The trend of incidence and mortality was analyzed using the Joinpoint model and the average annual percent change (AAPC).Results:From 2011 to 2020, 216 200 new cases of malignant tumors were reported in the elderly population in the cancer registration areas of Hebei Province, and 170 700 deaths were reported. The peak ages of incident cases number for males and females were 65-69 years old and 60-64 years old, respectively. The crude incidence rate of malignant tumors in the elderly was 905.42/10 5, and the crude mortality rate was 714.96/10 5. In general, the incidence and mortality in rural areas were higher than those in urban areas, and the incidence and mortality in males were higher than those in females. The peak ages of incidence and mortality were 80-84 years old and 85+ years old, respectively. From 2011 to 2020, lung cancer, gastric cancer, esophageal cancer, female breast cancer, and colorectal cancer were the main malignant tumors of incidence rate in the elderly population in Hebei Province, and lung cancer, gastric cancer, liver cancer, esophageal cancer, and colorectal cancer were the main malignant tumors in the mortality rate. From 2011 to 2020, the incidence and mortality of malignant tumors in the elderly population in Hebei Province showed a decreasing trend, and AAPC for the age-standardized incidence and mortality were -4.69% and -5.53%, respectively. The rank of incidence and mortality rate of each cancer had changed, but the top two were still lung cancer and stomach cancer. Conclusions:The incidence and mortality of cancer in the elderly population in Hebei province have decreased, but the burden is still heavy. Lung cancer and stomach cancer are still the focus of prevention and treatment in the elderly population in Hebei province.

Objective:To investigate the degree of satisfaction with courses of postgraduates in medicine in a military medical university, and to discuss the problems existing in the offering and teaching of postgraduate medical courses as well as targeted measures.Methods:A self-made questionnaire was administered through the Questionnaire Star platform to 533 postgraduate students in a military medical university to investigate the basic situation, the types of courses offered during their study period, their opinions about and degree of satisfaction with the curriculum system, the teaching effectiveness of various courses, and suggestions for improvement in education. SPSS 23.0 was used to perform the chi-square test to analyze the relationship between variables.Results:Among the 533 students, 391 (73.32%) were satisfied with course offering ( χ2=9.64, P=0.008), and 399 (74.95%) were satisfied with course teaching ( χ2=7.60, P=0.022). Twenty-four (4.47%), 3 (6.25%), 3 (10.81%), and 2 (6.45%) students in clinical medicine, public health and preventive medicine, nursing, and pharmacy, respectively, believed that course offerings did not quite fit with their majors. The numbers of students who believed that general compulsory courses, major-specific compulsory courses, and elective courses offered were appropriate in number were 309 (57.97%), 371 (69.61%), and 409 (76.74%), respectively. For the design of the curriculum system, 399 (74.86%), 367 (68.85%), 362 (67.92%), 361 (67.73%), 355 (66.61%), 352 (66.05%), and 357 (66.98%) were satisfied with "basic theory coverage", "major-specific knowledge coverage", "research interest cultivation", "innovative thinking cultivation", "academic reporting ability cultivation", "practical ability cultivation", and "academic writing ability cultivation", respectively. The numbers of master's and doctoral students who believed that there were appropriate numbers of courses on methodology and experimental skills were 285 (71.07%) and 90 (68.18%), respectively. Conclusions:In view of the current situation of postgraduate medical courses, general basic courses should be further optimized in terms of the number and proportion of different types of courses, and major-specific required courses should pay more attention to the cultivation of postgraduates' ability and quality in addition to the coverage of basic theories. Curriculum ideology and politics for medical postgraduates should be highlighted.

Parkinson's disease(PD)is the second most prevalent neurodegenerative disease and a major cause of movement disorders.Neuroinflammation plays an important role in the pathogenesis of PD.Icilin is a small molecule compound that has been reported to inhibit inflammation.Howev-er,its role in PD has not been reported.This study explored the effects of icilin on motor behavior,nerve damage,microglia activation,and neuroinflammation in MPTP-induced PD Meriones unguic-ulatus by behavioral experiments,immunohistochemistry,Western blot,and fluorescence quantifi-cation.The results showed that Icilin not only ameliorated motor dysfunction and neurological damage in MPTP-induced Meriones unguiculatus,but also inhibited microglia hyperactivation and its mediated neuroinflammation.The present study provides an evidence that icilin attenuates MPTP-induced neurodegenerative lesions in long-pawed gerbils,suggesting that it is a promising candidate for PD.

Objective To investigate the synergistic therapeutic effects of HER2 antibody-drug conjugate(HER2-ADC)combined with anti-PD-1 antibody(anti-PD-1)on HER2-expressing bladder cancer and elucidate its regulatory mechanisms on the tumor immune microenvironment.Methods Orthotopic tumor models were established in 40 female C57BL/6 mice(6～8 weeks old,body mass 18～22 g)using MB49 bladder cancer cells overexpressing human HER2.When tumors reached 100 mm3,the mice were randomized into(n=10)control(intraperitoneal injection of 1.0 mL PBS),anti-PD-1(200 μg per mouse every 3 d),HER2-ADC(2.5 mg/kg once weekly),and combination groups(same regimens as above monotherapy).Tumor volume and body mass were measured every 3 d during 28-day treatment.Tumor growth kinetics and survival rates were analyzed.Post-treatment survival was monitored until natural death to determine median survival time(n=5).At day 28,blood and tumor samples(n=5)were collected to detect myeloid-derived suppressor cells(MDSCs;CD11b?Gr1?)and regulatory T cells(Tregs;CD4?CD25?FOXP3?)with flow cytometry,tumor-infiltrating CD3?T,CD8?T,and FOXP3?T cells with immunohistochemical assasy,and liver/kidney functions[alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),creatinine(CRE)]and tissue damage indicators[lactate dehydrogenase isoenzyme(LDH-L)].Results In 28 d after treatment,the combination group obtained significantly smallest tumor volume than the control group and the 2 monotherapy groups(all P<0.01).The longest median survival was observed in the combination group(65 d,P<0.01),followed by the HER2-ADC group(55 d),anti-PD-1 group(53 d)and control group(41 d).After 28 d of treatment,the combination group exhibited obviously the smallest peripheral proportions of MDSCs/Tregs,most tumor-infiltrating CD3?T/CD8?T cells,and less FOXP3?T cells when compared with the 2 monotherapy groups and control group(all P<0.05).While,the 2 monotherapy groups had smaller MDSCs/Tregs proportions than the control group(P<0.05).No significant differences were observed among the 4 groups in serum ALT,AST,BUN,CRE,or LDH-L levels,and all of them were within normal ranges.Conclusion HER2-ADC combined with anti-PD-1 suppresses the growth of orthotopic bladder tumor,probably through their synergic effects on down-regulating MDSCs/Treg and enhancing CD8?T cell infiltration.

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People