Objective By using ultrasonography to calculate the ratio of optic nerve sheath diameter(ONSD)at 3 mm behind eyeball to the eyeball transverse diameter(ETD),based on which to evaluate the effect of dexmedetomidine on intracranial pressure(ICP)in patients with intracranial aneurysm after receiving interventional embolization under general anesthesia.Methods A total of 40 patients with intracranial aneurysm,who were scheduled to receive interventional embolization under general anesthesia at the Affiliated Lihuili Hospital of Ningbo University of China from May 2023 to November 2023,were selected for this study.By using random number table method,the patients were divided into control group(group C)and dexmedetomidine group(group D)with 20 patients in each group.Standardized anesthesia strategy was adopted in both groups.For patients of group D,a loading dose of dexmedetomidine was pumped at a velocity of 1 μg/(kg·h)for 10 min before the surgery,the pumping was continued at 0.5 μg/(kg·h)velocity during the operation,and the pumping stopped half an hour before the end of the operation.For patients of group C,the same anesthesia strategy was used,while no any special treatment was given.At the different time points,including before awakening(T0),immediately after extubation(T1),and 5 min(T2),10 min(T3),15 min(T4)after extubation,ONSD at 3 mm behind eyeball and ETD were measured by transorbital ultrasonography,and ONSD/ETD ratio was calculated to evaluate ICP.The mean arterial pressure(MAP),heart rate(HR),blood oxygen saturation(SPO2),severity of cough,and extubation time were recorded at the time to remove the catheter.Results Compared with the data obtained at T0,the ONSD/ETD ratios obtained at T1 and T2 were increased in both groups(P＜0.05),while the ONSD/ETD ratios obtained at other time points were not significantly different from the ONSD/ETD ratio obtained at T0(P＞0.05).Compared with Group C,in Group D the ONSD/ETD ratios obtained at T1 and T2 were smaller,the differences were statistically significant(P＜0.05).The incidence of moderate to severe cough in Group D was lower than that in Group C(P＜0.05).Compared with Group C,in Group D the HR and MAP determined at the time of removing catheter were lower(P＜0.05).The extubation time in Group D was longer than that in group C,the difference was statistically significant(P＜0.05).Conclusion ONSD/ETD ratio calculated by ultrasono-graphy can objectively reflect the changes of ICP during the extubation period.Dexmedetomidine can reduce the elevation degree of ICP through effectively inhibiting cough reflex and circulatory fluctuation during tracheal extubation.However,dexmedetomidine may increase the incidence of adverse events such as bradycardia,delayed extubation,etc.

Objective To evaluate the sensitivity,repeatability,anti-degradation ability,in vivo temporal stability,and tissue specificity of the DNA methylation sequencing panel constructed in our previous study for height inference,so as to provide a reference for forensic application.Methods Sensitivity:different initial template quantities(50 ng,40 ng,30 ng,20 ng)were set for sequencing.Repeatability:DNA from the same sample was sequenced three times.Anti-degradation ability:whole blood was used to make blood stains,and DNA was extracted and sequenced at 0,3,6 and 9 months,respectively.In vivo temporal stability:the blood was collected at 0,3,6,and 9 months for sequencing.Tissue specificities:published data and findings were used to analyze the tissue specificities of CpGs in the panel.Results The sensitivity test showed that the initial template quantities of 20 ng detected all the CpG sites and still obtained accurate prediction results.The results of the three repeated predictions of the same sample are stable,and the differences are mainly due to the randomness of the DNN model,indicating good detection repeatability.A complete methylation profile was obtained for the blood stains left at room temperature for 9 months,and the predicted results showed a small range of fluctuations.The three samples were predicted to fluctuate within a range of 1.5 cm or less over nine months.Tissue-specific analyses showed a high correlation between blood and saliva,but can not apply to other tissues.Conclusion The DNA methylation detection system we developed in our previous study has good sensitivity,repeatability,anti degradation ability,in vivo time stability,as well as strong tissue specificity,making it suitable for height inference of blood samples.This supports the feasibility of using targeted DNA methylation analysis on whole blood samples to infer height in the field of forensic science.

Objective This study aimed to investigate the tumorigenic properties of MMTV-PyMT breast cancer transgenic mice at different ages(in weeks)and the changes in the composition of immune cells in the tumor microenvironment.Methods Eight groups of 4,6,8,10,12,14,16 and 18 weeks of age MMTV-PyMT female mice(FVB mice as the background)and one group of 8 weeks of FVB female mice were prepared for routine blood testing,the pathological changes of the mammary gland and lung metastases were observed by histopathological sections,and the immune cells in blood,spleen,and tumor were analyzed by flow cytometry.Results MMTV-PyMT mice showed adenular ductal lesions at 4～6 weeks of age;the ductal portion expanded to the growth boundary at 8～9 weeks of age,and then gradually broke through the glandular boundary to form early breast cancer at 8～12 weeks of age,and advanced breast cancer at 10～14 weeks of age.At 12 weeks of age,metastases were visible in the lungs of some mice,and at 14 weeks of age,the number of metastases in the lungs increased significantly.As the age of the mice increased,the number of white blood cells,neutrophils,and platelets in their blood increased gradually,while the lymphocytes and erythrocytes showed a gradual downward trend.Flow cytometry showed that with the increase in age,the proportion of T cells in the spleen and tumor gradually decreased,the MDSCs in the blood,spleen,and tumor gradually increased,and the NK cells in the tumor also gradually increased.Conclusions This study analyzed routine blood tests,pathology,and immune cells in the tissues of MMTV-PyMT mouse models of different weeks of age,providing a novel perspective on the dynamic alterations of the tumor immune microenvironment during the malignant progression of breast cancer.

Objective To evaluate the sensitivity,repeatability,anti-degradation ability,in vivo temporal stability,and tissue specificity of the DNA methylation sequencing panel constructed in our previous study for height inference,so as to provide a reference for forensic application.Methods Sensitivity:different initial template quantities(50 ng,40 ng,30 ng,20 ng)were set for sequencing.Repeatability:DNA from the same sample was sequenced three times.Anti-degradation ability:whole blood was used to make blood stains,and DNA was extracted and sequenced at 0,3,6 and 9 months,respectively.In vivo temporal stability:the blood was collected at 0,3,6,and 9 months for sequencing.Tissue specificities:published data and findings were used to analyze the tissue specificities of CpGs in the panel.Results The sensitivity test showed that the initial template quantities of 20 ng detected all the CpG sites and still obtained accurate prediction results.The results of the three repeated predictions of the same sample are stable,and the differences are mainly due to the randomness of the DNN model,indicating good detection repeatability.A complete methylation profile was obtained for the blood stains left at room temperature for 9 months,and the predicted results showed a small range of fluctuations.The three samples were predicted to fluctuate within a range of 1.5 cm or less over nine months.Tissue-specific analyses showed a high correlation between blood and saliva,but can not apply to other tissues.Conclusion The DNA methylation detection system we developed in our previous study has good sensitivity,repeatability,anti degradation ability,in vivo time stability,as well as strong tissue specificity,making it suitable for height inference of blood samples.This supports the feasibility of using targeted DNA methylation analysis on whole blood samples to infer height in the field of forensic science.

Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.

Objective·To investigate the effects and molecular mechanisms of phosphatidylethanolamine(PE)on macrophage senescence and its senescence-associated secretory phenotype(SASP),as well as its pathophysiological role in liver injury.Methods·A macrophage senescence model was established using doxorubicin(DOX),followed by PE treatment.A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide(LPS)to investigate the effects of PE on liver injury.Senescence markers and SASP factors,including senescence-associated β-galactosidase(SA-β-gal),cell cycle inhibitor p21,tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6),were evaluated using SA-β-gal staining,quantitative real-time PCR,and Western blotting.RNA sequencing(RNA-seq)was performed,followed by Gene Ontology(GO)cellular component enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis(GSEA),to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence.The expression of endoplasmic reticulum(ER)stress-related proteins,including inositol-requiring enzyme 1 α(IRE1α),spliced X-box binding protein 1(XBP1s),activating transcription factor 6(ATF6),ATF4,and C/EBP homologous protein(CHOP),was analyzed through in vivo and in vitro experiments.Results·PE significantly promoted the expression of senescence markers SA-β-gal,p21,p16 and SASP factors.RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP.Further experiments demonstrated that PE activated the ER stress signaling pathway,promoting macrophage senescence and the expression of SASP factors.In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress.Conclusion·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway,thereby aggravating LPS-induced liver injury.

Objective This study aimed to investigate the tumorigenic properties of MMTV-PyMT breast cancer transgenic mice at different ages(in weeks)and the changes in the composition of immune cells in the tumor microenvironment.Methods Eight groups of 4,6,8,10,12,14,16 and 18 weeks of age MMTV-PyMT female mice(FVB mice as the background)and one group of 8 weeks of FVB female mice were prepared for routine blood testing,the pathological changes of the mammary gland and lung metastases were observed by histopathological sections,and the immune cells in blood,spleen,and tumor were analyzed by flow cytometry.Results MMTV-PyMT mice showed adenular ductal lesions at 4～6 weeks of age;the ductal portion expanded to the growth boundary at 8～9 weeks of age,and then gradually broke through the glandular boundary to form early breast cancer at 8～12 weeks of age,and advanced breast cancer at 10～14 weeks of age.At 12 weeks of age,metastases were visible in the lungs of some mice,and at 14 weeks of age,the number of metastases in the lungs increased significantly.As the age of the mice increased,the number of white blood cells,neutrophils,and platelets in their blood increased gradually,while the lymphocytes and erythrocytes showed a gradual downward trend.Flow cytometry showed that with the increase in age,the proportion of T cells in the spleen and tumor gradually decreased,the MDSCs in the blood,spleen,and tumor gradually increased,and the NK cells in the tumor also gradually increased.Conclusions This study analyzed routine blood tests,pathology,and immune cells in the tissues of MMTV-PyMT mouse models of different weeks of age,providing a novel perspective on the dynamic alterations of the tumor immune microenvironment during the malignant progression of breast cancer.

Objective This paper aims to explore patient satisfaction with mobile medical payments in ethnic minority areas and its influencing factors.Methods From May to August 2023,565 ethnic minority patients from 6 villages in 4 ethnic minority autonomous counties in Dehong Prefecture and Pu'er City,Yunnan Province,were selected as research subjects,and 186 Han patients in Kunming were selected as controls.The general information questionnaire,the mobile medical payment will-ingness and attitude survey scale,and the medical cost mobile payment satisfaction survey scale were used to investigate their sat-isfaction with actual situation of medical mobile payment.Additionally,this paper discussed influencing factors affecting satisfac-tion.Results The ethnic minority patients exhibited a significantly lower level of satisfaction compared to the Han patients(39.65±10.43 vs.49.54±7.88,P＜0.05).ethnic minority patients scored significantly lower on the dimensions of satisfac-tion,such as perceived safety,ease of use and usefulness of mobile medical payment compared to the group of Han patients(all P＜0.05).Additionally,they ethnic minority patients showed significantly lower level of willingness and attitude to use mobile medical payment compared to the group of Han patients(P＜0.05).The main factors influencing the significant difference in satisfaction with mobile medical payment were ethnic group,number of hospital visits in previous year,first-time use of mobile medical payment,and educational background(P＜0.05).Conclusion Ethnic minority patients have a low perception of secur-ity,ease of use,and usefulness of mobile medical payments,as well as a low willingness and characteristics for mobile medical payment.Therefore it is necessary to further enhance their experience and satisfaction.In the development of mobile medical pay-ment services hospitals should fully consider the current situation of"illiteracy""semi-illiteracy"and"lack of resources"in re-mote ethnic areas.They should actively develop service platforms and applications suitable for mobile medical payment in ethnic minority areas to continuously enhance service efficiency and quality.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To investigate the clinical, radiological, and pathological features of anaplastic gangliogliomas (AGGs) and to determine whether these tumors represent a distinct entity.Methods:Consecutive 667 cases of ganglioglioma (GG) diagnosed at the Xuanwu Hospital, Capital Medical University, Beijing, China between January 2015 and July 2023 were screened. Among these cases, 9 pathologically confirmed AGG cases were identified. Their clinical, radiological, treatment, and outcome data were analyzed retrospectively. Most of the tumor samples were subject to next-generation sequencing, while a subset of them were subject to DNA methylation profiling.Results:Among the 9 patients, there were five males and four females, with a median age of 8 years. Epileptic seizures (5/9) were the most frequently presented symptom. Radiological examinations showed three types of radiological manifestations: four cases showed abnormal MRI signals with no significant mass effects and mild enhancement; two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema, which showed significant heterogeneous enhancement and obvious mass effects, and one case displayed cystic cavity formation with nodules on MRI, which showed evident enhancements. All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway, including seven with BRAF p.V600E mutation and two with NF1 mutation. Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations, including three with CDKN2A homozygous deletion, one with a TERT promoter mutation, one with a H3F3A mutation, and one with a PTEN mutation.Conclusions:AGG exhibits a distinct spectrum of pathology, genetic mutations and clinical behaviors, differing from GG. Given these characteristics suggest that AGG may be a distinct tumor type, further expansion of the case series is needed. Therefore, a comprehensive integration of clinical, histological, and molecular analyses is required to correctly diagnose AGG. It will also help guide treatments and prognostication.