OBJECTIVE To observe the dynamic change trends of vancomycin resistance rates of Enterococcus fae-calis and Enterococcus faecium in medical institutions of Shanghai and nationwide based on the data from China Antimicrobial Resistance Surveillance System(CARSS)between 2014 and 2023 so as to provide bases for optimi-zing the prevention and control strategies for drug-resistant organisms.METHODS The data regarding to the van-comycin resistance rates of E.faecalis and E.faecium in Shanghai and nationwide were extracted from CARSS.The annual percentage change(APC),average annual percentage change(AAPC)and its 95％confi-dence interval(CI)were calculated by Joinpoint regression model(version 5.4.0).The differences in the changing trends and its statistical significance were analyzed.RESULTS The drug resistance rate of E.faecalis showed a re-markable and continuous decline in Shanghai(AAPC=-85.301％,P＜0.001),the isolation rate of the spe-cies maintained zero after 2019.The drug resistance rate nationwide showed a moderate decreasing amplitude(AAPC=-16.237％,P＜0.001),and there was no significant difference in the changing trend after 2019(P=0.628).The drug resistance rate of E.faecium showed a continuous decline trend in Shanghai(AAPC=-27.838％,P＜0.001),while the drug resistance rate nationwide firstly declined and then rose:with the decline from 2014 to 2020(APC=-18.476％,P＜0.001),the quick rebound from 2020 to 2023(APC=43.976％,P=0.005),and there was no significant difference in the overall change(AAPC=-1.459％,P=0.638).The decreasing amplitudes of drug resistance rates of the two species of Enterococcus were greater in Shanghai than nationwide(all P＜0.001),and the rebounds of drug resistance rates did not emerge nationwide.CONCLUSIONS Shanghai has achieved remarkable effect on control of drug resistance of Enterococcus through the management of antibiotics and infection control measures.The drug resistance rate of E.faecium re-bounds nationwide in recent years,indicating that the prevention and control should be strengthened in grass-roots medical institutions.It is suggested that Shanghai experience should be promoted,and the impact of transmis-sion mechanisms of drug resistance genes and COVID-19 epidemic on the use of antibiotics should be focused on.

Objective:To investigate the relevant factors for rupture of basilar tip aneurysms.Methods:This is a retrospective cohort study. Patients who underwent cerebrovascular digital subtraction angiography at Department of Cerebrovascular Disease Surgery,Zhujiang Hospital of Southern Medical University from July 2008 to February 2023 and were confirmed to have basilar tip aneurysms were retrospectively analyzed. There were 45 males and 56 females, aged (57.5±10.2) years (range: 36 to 76 years); the maximum diameter of the basilar tip aneurysm ( M(IQR)) was 6.85 (5.79) mm (range: 1.28 to 27.48 mm). Finally, 101 basilar tip aneurysms were included, and divided into two groups based on whether the basilar tip aneurysm ruptured or not. There were 37 cases (36.6%) in the ruptured group and 64 cases (63.4%) in the unruptured group. Data were analyzed using independent t-test, Mann-Whitney U test, chi-square test, or Fisher′s exact test, as appropriate, and predictive factors for rupture of basilar tip aneurysms were explored by Logistic regression analysis. Variance inflation factors was used for analysis of collinearity. Results:The univariate results showed statistically significant differences between the ruptured and unruptured groups in terms of aneurysm neck width, basilar artery diameter, mean diameter of the parental artery, the ratio of neck width to parent artery diameter, aneurysm width and maximum diameter of the aneurysm (all P<0.05). In multivariate analysis, basilar artery diameter ( OR=0.347, 95% CI:0.176 to 0.687, P=0.002), and NRP ( OR=0.366, 95% CI:0.192 to 0.696, P=0.002) were predictive factors for rupture of aneurysms occurring at the basilar tip. There was no multiple covariance between NRP and basilar artery diameter in the analysis of covariance (VIF=1). Conclusion:Smaller basilar artery diameter and smaller NRP are relevant factors for rupture of basilar tip aneurysms.

Objective To investigate the impact of immunohistochemical detection of omentin-1(omentin-1),secreted phosphoprotein 1(SPP1),and mismatch repair(MMR)protein expression status on the clinicopathological characteristics and prognosis of endometrial cancer(EC),in order to provide references for disease assessment,prognosis evaluation,and the development of molecular targeted therapies.Methods A total of 159 patients diagnosed with EC who were admitted to our hospital between December 2019 and December 2021 were enrolled as the study group.Additionally,152 samples of normal endometrial tissue were collected from patients undergoing hysterectomy due to benign uterine diseases and served as the control group.The expression levels of omentin-1,SPP1,and MMR proteins in endometrial tissues were compared among the study group,the control group,and EC patients with different clinicopathological characteristics and prognostic outcomes.Spearman correlation analysis was performed to evaluate the correlations among these biomarkers in EC tissues.The influencing factors of EC prognosis were analyzed through multivariate logistic regression.Kaplan-Meier survival curves were constructed to assess the association between the expression of these proteins and patient prognosis.Results The positive expression rate of SPP1 and the MMR deletion rate in endometrial tissues of the study group were significantly higher than those in the control group(P<0.05),while the positive expression rate of omentin-1 in endometrial tissues was significantly lower than that in the control group(P<0.05).In patients with EC exhibiting myometrial invasion≥1/2,the proportion of omentin-1 negativity was lower compared to omentin-1 positivity(P<0.05).Among EC patients with poorly differentiated tumors,the rates of SPP1 positivity and MMR deficiency were significantly increased(P<0.05).Spearman correlation analysis revealed that omentin-1 expression was negatively correlated with both MMR protein deletion and SPP1 overexpres-sion(P<0.05),whereas MMR deficiency was positively correlated with SPP1 overexpression(P<0.05).In the poor prognosis group,the positive expression rate of SPP1 and the deletion rate of MMR were elevated,while omentin-1 expression was reduced in endometrial tissues(P<0.05).The results of multivariate logistic analysis showed that omentin-1 negative,SPP1 positive,and MMR deletion were risk factors for the prognosis of EC patients(P<0.05).Kaplan-Meier survival curves were constructed based on follow-up data(Figures 1-3),indicating that patients with omentin-1 negativity,SPP1 positivity,and MMR deficiency had significantly worse prognoses(P<0.05).Conclusions With the development and progression of the clinicopathological features of EC,abnormalities were observed in the immunohistochemical expression of omentin-1,SPP1,and MMR proteins.Specifically,omentin-1 negativity,SPP1 positivity,and MMR protein deletion were associated with a poorer prognosis in EC patients.

Objective To investigate the therapeutic effect of folic acid combined with decitabine in diabetic retinop-athy(DR)mice with different methylenetetrahydrofolate reductase(MTHFR)genotypes.Methods The DR model mice were created by mating 20 MTHFR-/-mice with 20 wild-type C57 mice.A random number table method was employed to allocate 20 successfully modelled mice into the model group,DAC group,FA group,and FA+DAC group,with five mice assigned to each group.Five untreated MTHFR-/-and wild-type mice served as normal control.After constructing the DR model,the DAC group was injected intraperitoneally with 0.25 mg·kg-1 decitabine once every 5 days;the FA group was given 70 μg·kg-1 folic acid by tube feed once a day;the FA+DAC group was given 0.25 mg·kg-1 decitabine and 70μg·kg-1 folic acid at the same time;and the normal group was given an equal amount of physiological saline.All of the above groups were intervened for 30 days.OCT was employed for the measurement of retinal thickness,OCTA for retinal vascular density,histopathology(HE staining)for pathological changes in the mouse retina,real-time fluorescence quanti-tative PCR for mRNA expression,and Western blot analysis for protein expression levels.Results Compared with the wild-type model group,the degree of increase in retinal thickness and vascular density in the retinal layer was more pro-nounced in the MTHFR-/-mice model group(all P＜0.05).In wild-type mice,retinal thickness and retinal layer vessel den-sity were reduced in the DAC,FA and FA+DAC groups compared to the model group,with the FA+DAC group show-ing the greatest degree of reduction.The differences were all statistically significant(all P＜0.05);In MTHFR-/-mice,reti-nal thickness and vascular density in the retinal layer were reduced in the DAC group and the FA+DAC group compared to the model group(allP＜0.05).HE staining results showed an increased extent of retinal damage in the MTHFR-/-mice model group compared with the wild-type mice model group.Compared with the model group,the DAC group and the FA+DAC group had thinner retinas and more aligned ganglion cell layers in all types of mice,with the FA group having a worse effect and the FA+DAC group having a better treatment effect.The results of the polymerase chain reaction(PCR)revealed that the relative expression of the SAHH,MAT2A and DNMT1 proteins in the retinal tissues of the wildtype and MTHFR-/-mice model groups was elevated in comparison to the control group(all P＜0.05).Furthermore,the relative mR-NA expression of the DAC,FA and FA+DAC groups was reduced in comparison to the model group(all P＜0.05).In wild-type mice,the relative expression of MTHFR protein mRNA was decreased in the model group compared with the con-trol group,and increased in the DAC group,FA group,and FA+DAC group compared with the model group(all P＜0.05).Western blot results showed that the relative expression of DNMT1,MAT2A and SAHH proteins in the retinal tissues of the wild-type and MTHFR-/-mice model groups was higher than that of the control group(all P＜0.05),and the relative expression was lower in the DAC,FA,and FA+DAC groups compared with that in the model group(all P＜0.05).In wild-type mice,the relative expression of MTHFR protein in the retinal tissue of the model group was lower than that of the control group,and the relative expression of MTHFR protein in the FA group and the FA+DAC group was elevated com-pared with that of the model group(all P＜0.05).Conclusion The protective effect of folic acid combined with decit-abine on DR was superior to that of decitabine alone;treatment with folic acid in combination with decitabine may have yielded better efficacy in wild-type DR mice.

Objective:To investigate the efficacy and safety of off-label use of flow diverters (FDs) in aneurysms beyond the circle of Willis.Methods:Seventy-one patients with aneurysms beyond the circle of Willis treated with FDs from January 2016 to September 2023 at Department of Cerebrovascular Surgery, Neurosurgery Center (Zhujiang Hospital of Southern Medical University), Department of Neurosurgery (Guangdong Provincial People's Hospital), Department of Neurosurgery (First Affiliated Hospital of Chongqing Medical University), and Department of Neurosurgery (Beijing Tiantan Hospital, Capital Medical University) were selected. The clinical and imaging data of these patients were analyzed retrospectively, and the clinical characteristics, aneurysm characteristics, endovascular treatments, perioperative complications, and clinical and imaging follow-up results were summarized and analyzed.Results:Among the 71 patients, 22 (31.0%) had ischemic stroke history and 43 (60.6%) had hypertension history. A total of 76 aneurysms were found, including 5 aneurysms (6.6%) at the anterior communicating artery, 10 (13.2%) at the anterior cerebral artery, 53 (69.7%) at the middle cerebral artery, and 8 (10.5%) at the posterior cerebral artery. The median aneurysm size (Inter Quartile Range) was 5.65 (3.63, 10.12) mm, and mean diameter of the parent artery was (2.70±0.57) mm. A total of 80 FDs were used, including 38 (47.5%) Pipeline embolization devices and 42 (52.5%) Tubridge embolization devices; the implantation success rate was 98.8% (79/80). Seven patients (9.9%) had perioperative complications, of which 2 (2.8%) were permanent (1 patient with visual field defect and 1 patient with intracranial hemorrhage). Seventy-one patients had clinical follow-up for (19.73±11.90) months, of which 68 patients (95.8%) had good outcome (modified Rankin scale score of 0-2), 10 patients (14.1%) had ischemic complications, and one patient (1.4%) had hemorrhage complications. Sixty-seven aneurysms (88.2%) underwent angiographic follow-up for 7 (6-12) months, of which 44 aneurysms (65.7%) were completely occluded and 10 (14.9%) had in-stent stenosis.Conclusion:The results of this study preliminarily confirm that off-label use of FDs is relatively safe and effective in aneurysms beyond the circle of Willis.

Objective:To evaluate the efficacy and safety of intrasaccular flow disruptor in wide-necked intracranial aneurysms.Methods:One hundred and seventeen patients with wide-necked intracranial aneurysms treated with intrasaccular flow disruptor were collected from Department of Neurointervention (First Affiliated Hospital of Zhengzhou University), Department of Neurosurgery (Beijing Tiantan Hospital, Capital Medical University), Department of Cerebrovascular Surgery, Neurosurgery Center (Zhujiang Hospital, Southern Medical University), and Department of Neurosurgery (First Affiliated Hospital of Harbin Medical University) from August 2022 to March 2024. Raymond-Roy Occlusion Classification (RROC) was employed to evaluate aneurysm embolization immediately after procedure; cranial CT or MRI within 48 hours of embolization were performed to identify any new intracranial hemorrhage, subarachnoid hemorrhage, or new symptomatic cerebral infarction related to the intracranial aneurysms. Modified Rankin Scale (mRS) was used to assess the neurological function at discharge. Imaging follow-up and outpatient follow-up were performed at 6 months after embolization to evaluate the aneurysm occlusion degree and complications.Results:A total of 117 intrasaccular flow disruptors were implanted in 117 patients, with a technical success rate of 100%; 115 patients (98.3%) enjoyed successful one-time release of their disruptors, and 2 patients (1.7%) required retrieval and redirection of the disruptors before second successful attempt. Flow disruptor plus stent was performed in 13 patients (11.1%). Immediately after procedure, RROC grading I was noted in 3 patients, grading II in 51 patients and grading III in 63 patients. Cranial CT or MRI within 48 hours of embolization indicated no new intracranial hemorrhage, subarachnoid hemorrhage, or symptomatic cerebral infarction related to the intracranial aneurysms. All patients had mRS score of 0 at discharge. Eighty-three patients completed a 6-month follow-up (RROC grading I in 41 patients, grading II in 33 patients and grading III in 9 patients), without ischemic or hemorrhagic adverse events.Conclusion:The results of this study preliminarily suggest that intrasaccular flow disruptor is effective and safe in wide-necked intracranial aneurysms.

Objective:To explore the efficacy and safety of embolization of anterior cranial fossa dural arteriovenous fistula (ACF-DAVF) via different arterial approaches, and provide evidence for individualized treatment of ACF-DAVF. Methods:A retrospective study was performed; 25 patients with ACF-DAVF admitted to Department of Cerebrovascular Surgery, Neurosurgery Center, Zhujiang Hospital, Southern Medical University from January 2020 to December 2023 were enrolled. Vascular approaches, including the anterior cerebral artery ( n=7), facial artery ( n=3), middle meningeal artery ( n=8), ophthalmic artery ( n=6), and vein ( n=1), were selected based on angioarchitectural features and microcatheter accessibility. Fistula and proximal draining vein occlusions were confirmed by immediate post-embolization digital subtraction angiography (DSA), and perioperative complications were recorded. At a 6-month follow-up, prognoses were assessed by modified Rankin Scale (mRS), and DSA or MRA was performed to detect the recurrence of ACF-DAVF. Results:Six patients had complete embolization and 2 patients had near-total embolization of the fistula and proximal draining vein immediately after embolization via middle meningeal artery approach; 4 patients achieved complete embolization and 2 patients achieved near-total embolization via ophthalmic artery approach; 6 patients achieved complete embolization and one patient achieved near-total embolization via anterior cerebral artery approach; 3 patients achieved complete embolization via facial artery approach; one patient achieved complete embolization via venous approach. No perioperative intracranial hemorrhage or central retinal artery occlusion was noted. Follow-up for 6 months was performed in 25 patients: mRS score was 0 in 19 patients, 1 in 2 patients, and 2 in 4 patients; DSA in 19 patients and MRA in 6 patients indicated no ACF-DAVF recurrence. Conclusion:Based on the angioarchitectural features and microcatheter accessibility, individualized selection of vascular approaches for ACF-DAVF embolization can achieve better efficacy and safety.

Flow diverter (FD) devices have gradually become the mainstream approach for interventional treatment of intracranial aneurysms. In-stent stenosis (ISS) is a common complication after FD implantation, which can lead to ischemic events and affect the prognosis of patients. Current studies have shown that ISS occurrence is closely related to hemodynamic changes. From the perspective of hemodynamics, this article reviews the research progress of mechanisms, evaluation methods and treatments of ISS after FD implantation, in order to provide reference for clinical practice.

Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

Cold tumors have a poor response to tumor immunotherapy due to low immune cell infiltration and the ability to evade immune attacks. Converting cold tumors into hot tumors can enhance the clinical effectiveness of anti-tumor immunotherapy. High-intensity focused ultrasound (HIFU) as a non-invasive treatment can damage tumors through mechanical effects, but there is a lack of research on its cytotoxic mechanisms at the cellular level and its role in inducing anti-immune responses. In this study, the role of HIFU in triggering tumor ferroptosis by disrupting the GSH/GSSG balance through mechanochemical action and the associated anti-tumor immune priming effect were investigated. The use of a nano-enhancer loaded with PFOB combined with HIFU could enhance ferroptosis in triple-negative breast cancer at a specific stage of tumor growth (UTGR = 0) while promoting the conversion of a cold tumor into a hot tumor, thereby improving the immune response. Overall, this provides valuable guidance for the clinical application of HIFU in tumor immunotherapy.