Aim To explore the effects of nuciferine on cognitive behavior and the underlying mechanisms,white matter injury(WMI),neuroinflammation,and ferroptosis in mice with chronic ischemic WMI.Meth-ods Sixty C57BL/6 mice were divided into a control group,a bilateral common carotid artery stenosis(BCAS)model group,and low/high-dose nuciferine groups(20/40 mg·kg-1).A chronic ischemic WMI model was established using BCAS surgery.Following eight weeks of treatment,cognitive behavior(Y-maze,novel object recognition,Morris water maze),white matter integrity(LFB/MBP staining),microglial acti-vation(Iba-1 immunofluorescence),inflammatory cy-tokines(ELISA for TNF-α,IL-1β,IL-6),ferroptosis markers(Fe2+,ROS,MDA,GSH),mitochondrial ultrastructure(electron microscopy),and protein ex-pression of the PI3K/Akt and NRF2/xCT/GPX4 signa-ling pathways(Western blot)were evaluated.Results Compared with the control group,the BCAS group showed significant cognitive decline(P＜0.05),re-duced myelin density,elevated inflammatory cytokines and ferroptosis markers(Fe2+,ROS,MDA),shrunk-en mitochondria,and downregulated PI3K/Akt and NRF2/xCT/GPX4 pathway proteins(P＜0.05).Nu-ciferine intervention significantly ameliorated these in-juries in BCAS mice,with the high-dose group exhibi-ting superior effects(P＜0.05).Conclusions Nu-ciferine exerts protective effects against chronic ische-mic WMI and cognitive impairment by activating the PI3K/Akt and NRF2/xCT/GPX4 signaling pathways,thereby suppressing neuroinflammation and ferroptosis.

Objective To explore influencing factors in diagnosing stump vaginal lesions by comparing the clinical data of patients with vaginal wall resection after total hysterectomy.Methods This retrospective study included patients who underwent vaginectomy due to stump vaginal lesions[including high-grade intraepithelial lesion(HSIL)or cancer]in Obstetrics and Gynecology Hospital,Fudan University between Jan 1,2013 and Sep 30,2022.The diagnosis was confirmed based on pathology results after vaginal stump resection,then patients were categorized into HSIL group and vaginal cancer(VC)group.We analyzed the differences in clinical features between the groups and evaluated the diagnostic value of various indicators for vaginal cancer.Additionally,within the VC group,patients whose colposcopic biopsy showed HSIL while whose pathology upgraded to invasive cancer after stump colpotomy were classified as the high-grade pathologic invasive cancer group(HC group).We then compared the HSIL group and the HC group to assess the predictive value of each index for pathological escalation.Results Significant differences were observed between the HSIL and VC groups in terms of age,etiology of previous hysterectomy,proportion of clinical symptoms,proportion of abnormal physical examination findings,proportion of abnormal imaging findings,proportion of papillary lesions,proportion of vaginal roof lesions,and squamous cell carcinoma antigen(SCCA)(P<0.05).However,there were no significant differences in fertility,previous hysterectomy,or HPV infection rate.Abnormal physical examination and imaging findings demonstrated better diagnostic performance(AUC>0.7).The proportion of vaginal apex lesions was significantly higher in the HC group compared with the HSIL group(P<0.05).Conclusion Previous hysterectomy for cervical cancer,presence of clinical symptoms,abnormal physical findings,abnormal imaging manifestations,and lesions at the vaginal apex are significant influencing factors in the diagnosis of vaginal stump carcinoma.Although colposcopy remains the primary diagnostic method,vaginal resection should be considered to rule out invasive carcinoma when high-risk factors exist,even if colposcopic biopsy pathology suggests HSIL.

In July 2024,the Diagnosis Related Groups(DRG)2.0 is released based on the Notice from the National Healthcare Security Administration on Issuing the DRG 2.0 and Deepening the Relevant Work.Compared with DRG 1.1,version 2.0 was established based on a wider range of suggestions regarding the Adjacent Diagnosis Related Groups(ADRG),Major Comorbidity or Complication(MCC),and Comorbidity or Complication(CC)from various institutions.A list of disease diagnoses and surgical operations that are not used as grouping rules was compiled,and grouping efficacy was further improved by upgrading the algorithms for MCC and CC with the help of AI.Meanwhile,it is necessary to pay more attention to the number of cases of ADRG,the better methods to list the MCC/CC,the suggestions of various doctors and continuously standardize the data and update the grouping scheme of DRG.

Objective:To explore the coordinated development status of the medical service supply-economy-society trinity systems in Zhejiang Common Prosperity Demonstration Zone,and to offer references for formulating policies conducive to the efficient and coordinated development of these three systems.Methods:Based on the panel data from 2013 to 2022,this research was conducted on the 11 prefectural-level cities in Zhejiang Province.Firstly,an evaluation index system for the three systems was established,and the entropy method was employed to determine the weights of each index and calculate the comprehensive evaluation index.Secondly,a triangular model was introduced to delineate the relative relationships among the three systems,and the coupling coordination degree model was utilized to disclose the coordination degree of the three systems.Finally,the spatial autocorrelation analysis method was applied to investigate the spatial autocorrelation of the coupling coordination degree of the three systems.Results:(1)On the whole,the development status of the three systems has improved over time,yet the comprehensive development level remains to be improved.(2)Overall,each prefectural-level city has transited from a medical service supply-society-dominated development to a balanced and coordinated development of the medical service supply-economy-society trinity systems.The coupling coordination degree of the three systems has risen from 0.468(on the verge of imbalance)in 2013 to 0.609(primary coordination)in 2022,presenting an upward trend in general.However,the coordination level remains to be improved and there exist imbalances among regions.(3)The coupling coordination degree of the three systems in Zhejiang Province exhibits a significant positive spatial correlation,and the spatial distribution characteristics are relatively stable. Conclusion:The coupling coordination degree of the medical service supply-economy-society trinity systems in Zhejiang Province awaits further enhancement. At the level of Zhejiang Province,favorable policy support should be provided,the layout of medical resources should be rationally planned,and high-quality economic and social development should be promoted. Each prefectural-level city should formulate strategies for medical service supply,economic,and social development in accordance with its own development level and local conditions,strengthen inter-city linkage and cooperation,and thereby elevate the coordinated development level of the three systems.

Aim To explore the effects of nuciferine on cognitive behavior and the underlying mechanisms,white matter injury(WMI),neuroinflammation,and ferroptosis in mice with chronic ischemic WMI.Meth-ods Sixty C57BL/6 mice were divided into a control group,a bilateral common carotid artery stenosis(BCAS)model group,and low/high-dose nuciferine groups(20/40 mg·kg-1).A chronic ischemic WMI model was established using BCAS surgery.Following eight weeks of treatment,cognitive behavior(Y-maze,novel object recognition,Morris water maze),white matter integrity(LFB/MBP staining),microglial acti-vation(Iba-1 immunofluorescence),inflammatory cy-tokines(ELISA for TNF-α,IL-1β,IL-6),ferroptosis markers(Fe2+,ROS,MDA,GSH),mitochondrial ultrastructure(electron microscopy),and protein ex-pression of the PI3K/Akt and NRF2/xCT/GPX4 signa-ling pathways(Western blot)were evaluated.Results Compared with the control group,the BCAS group showed significant cognitive decline(P＜0.05),re-duced myelin density,elevated inflammatory cytokines and ferroptosis markers(Fe2+,ROS,MDA),shrunk-en mitochondria,and downregulated PI3K/Akt and NRF2/xCT/GPX4 pathway proteins(P＜0.05).Nu-ciferine intervention significantly ameliorated these in-juries in BCAS mice,with the high-dose group exhibi-ting superior effects(P＜0.05).Conclusions Nu-ciferine exerts protective effects against chronic ische-mic WMI and cognitive impairment by activating the PI3K/Akt and NRF2/xCT/GPX4 signaling pathways,thereby suppressing neuroinflammation and ferroptosis.

Objective To explore influencing factors in diagnosing stump vaginal lesions by comparing the clinical data of patients with vaginal wall resection after total hysterectomy.Methods This retrospective study included patients who underwent vaginectomy due to stump vaginal lesions[including high-grade intraepithelial lesion(HSIL)or cancer]in Obstetrics and Gynecology Hospital,Fudan University between Jan 1,2013 and Sep 30,2022.The diagnosis was confirmed based on pathology results after vaginal stump resection,then patients were categorized into HSIL group and vaginal cancer(VC)group.We analyzed the differences in clinical features between the groups and evaluated the diagnostic value of various indicators for vaginal cancer.Additionally,within the VC group,patients whose colposcopic biopsy showed HSIL while whose pathology upgraded to invasive cancer after stump colpotomy were classified as the high-grade pathologic invasive cancer group(HC group).We then compared the HSIL group and the HC group to assess the predictive value of each index for pathological escalation.Results Significant differences were observed between the HSIL and VC groups in terms of age,etiology of previous hysterectomy,proportion of clinical symptoms,proportion of abnormal physical examination findings,proportion of abnormal imaging findings,proportion of papillary lesions,proportion of vaginal roof lesions,and squamous cell carcinoma antigen(SCCA)(P<0.05).However,there were no significant differences in fertility,previous hysterectomy,or HPV infection rate.Abnormal physical examination and imaging findings demonstrated better diagnostic performance(AUC>0.7).The proportion of vaginal apex lesions was significantly higher in the HC group compared with the HSIL group(P<0.05).Conclusion Previous hysterectomy for cervical cancer,presence of clinical symptoms,abnormal physical findings,abnormal imaging manifestations,and lesions at the vaginal apex are significant influencing factors in the diagnosis of vaginal stump carcinoma.Although colposcopy remains the primary diagnostic method,vaginal resection should be considered to rule out invasive carcinoma when high-risk factors exist,even if colposcopic biopsy pathology suggests HSIL.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Three typical failures of large-aperture 16-slice spiral Siemens SOMATOM Sensation Open CT were introduced in terms of phenomenon,cause and treatment method.References were provided for medical engineers to treat similar failures.

Objective This study aimed to investigate whether Trichinella spiralis Ts87 protein can facilitate immune evasion by degrading the mouse neutrophil extracellular traps(NETs).Methods First,we used bioinformatics tools to analyze the physicochemical properties of Ts87 and,through sequence homology alignment,confirmed its classification within the nuclease family.Molecular cloning and protein purification techniques were then employed to obtain high-purity Ts87 protein,and its nuclease activity was confirmed.Additionally,we compared the primary sequence of Ts87 with known active sites from human lysosomal DNase IIα and the structurally characterized Burkholderia thailandensis DNase II.This enabled us to predict potential active sites.Ts87 enzymatic mutants were generated using site-directed mutagenesis,and their functions were confirmed through enzymatic activity experiments.The extracellular nucleic acid content of mouse bone marrow neutrophils and the immunofluorescence staining of mouse NETs were assessed in vitro to verify whether the Ts87 protease mutants exhibited a decreased ability to degrade NETs.Finally,after immunizing mice with Ts87,calculated larvae burden and the degradation of NETs in vivo were observed by immunostaining the MPO and CitH3 expression in the intestinal NETs of the mice.Results High-purity Ts87 protein was successfully obtained and confirmed to possess nuclease activity,capable of degrading NETs in vitro.The Ts87 mutants exhibited reduced capacity in degrading NETs.In vivo experiments in mice demonstrated that the production of anti-Ts87 antibodies in immunized mice reduced the degradation of NETs,facilitating NET-mediated attack on the parasites and resulting in decreased larvae burden in the mice.Conclusions Trichinella spiralis can utilize Ts87 nuclease to evade capture by NETs,providing potential vaccine and drug targets for the prevention and treatment of trichinellosis.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.