As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases and therapeutic responses. Although numerous probes are available for imaging pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an ¹⁸F-labeled PET tracer (QTFT) that targets the P2Y₁₂, a receptor highly expressed on anti-inflammatory microglia. [¹⁸F]QTFT exhibited high binding affinity to the P2Y₁₂ (14.43 nmol/L) and superior blood-brain barrier permeability compared to other candidates. Micro-PET imaging in IL-4-induced neuroinflammation models showed higher [¹⁸F]QTFT uptake in lesions compared to the contralateral normal brain tissues. Importantly, this specific uptake could be blocked by QTFT or a P2Y₁₂ antagonist. Furthermore, [¹⁸F]QTFT visualized brain lesions in mouse models of epilepsy, glioma, and aging by targeting the aberrantly expressed P2Y₁₂ in anti-inflammatory microglia. In a pilot clinical study, [¹⁸F]QTFT successfully located epileptic foci, showing enhanced radioactive signals in a patient with epilepsy. Collectively, these studies suggest that [¹⁸F]QTFT could serve as a valuable diagnostic tool for imaging various brain disorders by targeting P2Y₁₂ overexpressed in anti-inflammatory microglia.

Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe^-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals ; Atherosclerosis/prevention & control* ; Mice ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Signal Transduction/drug effects* ; Anthraquinones/pharmacology* ; Humans ; Integrin beta1/metabolism* ; Epithelial-Mesenchymal Transition/drug effects* ; Male ; Transforming Growth Factor beta/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Human Umbilical Vein Endothelial Cells/drug effects*

OBJECTIVE: To compare the effectiveness of poly ether ether ketone (PEEK) localization marker combined with mixed reality technology versus color doppler ultrasound guidance for the vessel localization of anterolateral thigh perforator flap. METHODS: A retrospective analysis was conducted on 40 patients with tissue defects after oral cancer resection who underwent repair using the anterolateral thigh perforator flap between January 2022 and June 2023. According to the different intraoperative positioning methods of the anterolateral thigh perforator flap, they were randomly divided into PEEK group [using PEEK localization marker combined with mixed reality technology based on CT angiography (CTA) data] and color ultrasound group (using color ultrasound guidance), with 20 cases in each group. There was no significant difference in gender, age, etiology, and disease duration between the two groups ( P>0.05). The number of perforator vessels identified in the two groups of regions of interest was recorded, and compared them with the intraoperative actually detected number to calculate the success identifying rate of perforator vessels; the distance between the perforating point and the actual puncture point was measured, the operation time of the two groups of flaps was recorded. RESULTS: In the PEEK group, 32 perforator vessels were identified, 34 were detected by intraoperative exploration, and the success identifying rate was 94.1% (32/34); in the color ultrasound group, 29 perforator vessels were identified, 33 were detected by intraoperative exploration, and the success identifying rate was 87.8% (29/33); there was a significant difference in the success identifying rate between the two groups ( P<0.05). The distance between the perforating point and the actual puncture point and the operation time in PEEK group were significantly shorter than those in color ultrasound group ( P<0.05). Patients in both groups were followed up 6-30 months, with a median of 17 months; there was no significant difference in follow-up time between the two groups ( P>0.05). In the PEEK group, there was 1 case of flap necrosis at the distal edge and delayed healing after trimming and dressing change. In the color ultrasound group, there was 1 case of flap necrosis at 7 days after operation and pectoralis major myocutaneous flap was selected for repair after removal of the necrotic flap. In the rest, the flap survived and the incision healed by first intention. Donor site infection occurred in 1 case in PEEK group and healed after anti-inflammatory treatment. The maxillofacial appearance of the two groups was good, the flap was not obviously bloated, and the patients were satisfied with the repair effect. CONCLUSION Compared with the traditional color ultrasound guidance, the PEEK localization marker combined with mixed reality technology based on CTA data in vessel localization of anterolateral thigh perforator flap has higher success identifying rate and positioning accuracy, and the flap production time is shorter, which has high clinical application value.
Humans ; Ketones ; Perforator Flap/blood supply* ; Benzophenones ; Polymers ; Male ; Thigh/blood supply* ; Polyethylene Glycols ; Female ; Ultrasonography, Doppler, Color ; Computed Tomography Angiography ; Plastic Surgery Procedures/methods* ; Mouth Neoplasms/surgery* ; Middle Aged

Objective:To establish Chinese grading standards for elderly disability and dementia, in accordance with the International Classification of Functioning, Disability and Health(ICF)items, and to develop visual assessment tools that can be easily understood by patients, family members, and health workers.The aim is to verify the reliability and validity of these tools.Methods:In this study, we established five categories of elderly disability classification, along with corresponding ICF items and visual evaluation tools.The appropriateness and compatibility of the tools were assessed using questionnaires, which included illustrations, GIF dynamic pictures, and ICF items.Correlation analysis was conducted to screen the items, and the validity of the visual evaluation tools was determined through a picture-text matching validity test.Reliability was evaluated using internal consistency or test-retest reliability, and validity was assessed through content validity.Results:Each grade of disability was initially divided into five levels.However, after expert consultations and classification revision, each level was ultimately simplified into four levels with clearer descriptions.The Pearson correlation coefficients between all items and the total scores of each part were found to exceed 0.3, and the difference was statistically significant(all P<0.05).The average and mode of the illustrations and GIF dynamic pictures, when matched with related descriptions, were both above 3, with consistency rates surpassing 50%.Statistical differences were observed in eight items between the two visual assessment tools.The Cronbach's α coefficients, which reflect internal consistency, were all above 0.60.The intra-group correlation coefficients, which indicate test-retest reliability, were all greater than 0.70.The content validity index of the questionnaire at the overall level was above 0.90, while the item-level content validity index was more than 0.78. Conclusions:The Chinese grading standards for elderly disability and dementia, which are aligned with the ICF, have been preliminarily established.Visual assessment tools have also been developed, which demonstrate good reliability and validity.Among the two visual assessment tools, GIF dynamic pictures were found to be more popular and easier to understand.

Objective:To systematically evaluate the efficacy and safety of carfilzomib in treating relapsed and/or refractory multiple myeloma (RRMM) in the real world.Methods:Relevant databases at home and abroad were searched (up to April 2023), and the literature on real-world studies of carfilzomib in the treatment of RRMM was collected. The quality of the literature was evaluated with the methodological index for non-randomized studies (MINORS) scale. Research data on the effectiveness and safety in RRMM patients treated with carfilzomib were extracted. The effectiveness indicators included the overall response rate (ORR), median progression-free survival (PFS), and overall survival (OS). The safety indicators included the incidence of adverse events (AEs) and the rate of treatment termination due to AEs, etc. Stata 13.0 software was used for meta-analysis of single proportions, and the occurrence of major adverse events was analyzed by descriptive statistics.Results:A total of 12 studies were entered, including 2 615 patients. The quality evaluation results showed that all of the 12 studies were with high quality. The meta-analysis of single proportions showed that ORR of carfilzomib in the treatment of RRMM was 75%[95% confidence interval ( CI): 68%-82%], the incidence of ≥ grade 3 AEs was 46% (95 %CI: 44%-49%), and the incidence of treatment termination due to AEs was 14% (95 %CI: 10%-19%). AEs with an incidence of >5% included thrombocytopenia, anemia, neutropenia, infection, hypertension, liver injury, and kidney injury. Conclusions:In the real world, the efficacy of carfilzomib in the treatment of RRMM is lower than that in clinical trials. The occurrence of infection during carfilzomib treatment and drug toxicity to the hematological system, cardiovascular system, liver, and kidney need to be paid attention to.

Objective:To systematically evaluate the efficacy and safety of carfilzomib in treating relapsed and/or refractory multiple myeloma (RRMM) in the real world.Methods:Relevant databases at home and abroad were searched (up to April 2023), and the literature on real-world studies of carfilzomib in the treatment of RRMM was collected. The quality of the literature was evaluated with the methodological index for non-randomized studies (MINORS) scale. Research data on the effectiveness and safety in RRMM patients treated with carfilzomib were extracted. The effectiveness indicators included the overall response rate (ORR), median progression-free survival (PFS), and overall survival (OS). The safety indicators included the incidence of adverse events (AEs) and the rate of treatment termination due to AEs, etc. Stata 13.0 software was used for meta-analysis of single proportions, and the occurrence of major adverse events was analyzed by descriptive statistics.Results:A total of 12 studies were entered, including 2 615 patients. The quality evaluation results showed that all of the 12 studies were with high quality. The meta-analysis of single proportions showed that ORR of carfilzomib in the treatment of RRMM was 75%[95% confidence interval ( CI): 68%-82%], the incidence of ≥ grade 3 AEs was 46% (95 %CI: 44%-49%), and the incidence of treatment termination due to AEs was 14% (95 %CI: 10%-19%). AEs with an incidence of >5% included thrombocytopenia, anemia, neutropenia, infection, hypertension, liver injury, and kidney injury. Conclusions:In the real world, the efficacy of carfilzomib in the treatment of RRMM is lower than that in clinical trials. The occurrence of infection during carfilzomib treatment and drug toxicity to the hematological system, cardiovascular system, liver, and kidney need to be paid attention to.

To summarize the nursing experience of an adolescent with early repolarization syndrome who had implanted a subcutaneous implantable cardioverter defibrillator(ICD)and experiences frequent ventricular fibrillation.The main nursing care were as follows:recognizing a ventricular fibrillation attack and emergency care;risk prevention and handling in transportation;prevention of iatrogenic infection and strengthening protective isolation;promoting the recovery of brain function;personalized health education;pre-hospital first aid skills training for families.After careful treatment and nursing,the patient did not recur arrhythmia,and heart function had improved significantly,and the pulmonary inflammation disappeared.No medical-acquired infections occurred during hospitalization.The patient's motor ability and language expression ability recovered to the baseline,and was discharged on the 20th day of admission.A month after discharge,the patient recovered well and could study and live normally.

Objective:To systematically evaluate the efficacy and safety of ixazomib in patients with relapsed or refractory multiple myeloma (RRMM) in the real world.Methods:Relevant databases at home and abroad were searched (up to April 2022), and the literature on real-world studies of ixazomib in the treatment of RRMM was collected. The quality of the literature was evaluated with the methodological index for non-randomized studies (MINORS) scale. Data such as the effectiveness rate and incidence of adverse events in RRMM patients treated with ixazomib were extracted. The effectiveness indicators included the overall response rate (ORR), very good partial response or better (≥VGPR) rate and median progression-free survival (PFS). The safety indicators included the incidence of adverse events (AEs) and the rate of treatment termination due to AEs, etc. Stata 13.0 software was used for meta-analysis of single proportions, and the occurrence of major adverse events was analyzed by descriptive statistics.Results:A total of 12 studies were entered, including 1 006 patients. The quality evaluation results showed that all of the 12 studies were with high quality. The meta-analysis of single proportions showed that ORR of ixazomib in the treatment of RRMM was 65%[95% confidence interval ( CI): 58%-72%], ≥VGPR rate was 32% (95% CI: 25%-38%), the median PFS was 21.73 (95% CI: 14.37-29.08) months, the incidence of ≥ grade 3 AEs was 39% (95% CI: 24%-55%), and the incidence of treatment termination due to AEs was 6% (95% CI: 3%-10%). AEs with an incidence of ≥10% included neutropenia, thrombocytopenia, infection, anemia, diarrhea, fatigue, peripheral neuropathy, rashes, and bone pain. Conclusion:In the real world, the efficacy of ixazomib in the treatment of RRMM is lower than that in clinical trials, but the safety is similar.

Objective:To systematically evaluate the efficacy and safety of ixazomib in patients with relapsed or refractory multiple myeloma (RRMM) in the real world.Methods:Relevant databases at home and abroad were searched (up to April 2022), and the literature on real-world studies of ixazomib in the treatment of RRMM was collected. The quality of the literature was evaluated with the methodological index for non-randomized studies (MINORS) scale. Data such as the effectiveness rate and incidence of adverse events in RRMM patients treated with ixazomib were extracted. The effectiveness indicators included the overall response rate (ORR), very good partial response or better (≥VGPR) rate and median progression-free survival (PFS). The safety indicators included the incidence of adverse events (AEs) and the rate of treatment termination due to AEs, etc. Stata 13.0 software was used for meta-analysis of single proportions, and the occurrence of major adverse events was analyzed by descriptive statistics.Results:A total of 12 studies were entered, including 1 006 patients. The quality evaluation results showed that all of the 12 studies were with high quality. The meta-analysis of single proportions showed that ORR of ixazomib in the treatment of RRMM was 65%[95% confidence interval ( CI): 58%-72%], ≥VGPR rate was 32% (95% CI: 25%-38%), the median PFS was 21.73 (95% CI: 14.37-29.08) months, the incidence of ≥ grade 3 AEs was 39% (95% CI: 24%-55%), and the incidence of treatment termination due to AEs was 6% (95% CI: 3%-10%). AEs with an incidence of ≥10% included neutropenia, thrombocytopenia, infection, anemia, diarrhea, fatigue, peripheral neuropathy, rashes, and bone pain. Conclusion:In the real world, the efficacy of ixazomib in the treatment of RRMM is lower than that in clinical trials, but the safety is similar.

Objective:To investigate the change of the detection rate of colorectal cancer (CRC), colorectal adenoma and advanced adenoma in adults under colonoscopy in Shihezi in the past ten years.Methods:Data of patients who completed colonoscopy in the First Affiliated Hospital of Shihezi University School of Medicine from January 1, 2010 to December 31, 2019 were investigated. The medical records were collected by consulting the electronic medical record system, including the age and sex of patients and the location, quantity, size and pathological type of lesions. The detection rates, including the overall detection rate in the past 10 years, those in the first 5 years (from 2010 to 2014) and the second 5 years (from 2015 to 2019) of colorectal adenomas, advanced colorectal adenomas and CRC, were studied.Results:A total of 50 645 cases were included, 14 931 cases were excluded by the exclusion criteria, and finally a total of 35 714 cases were included in the data analysis. The 10-year overall detection rates of colorectal adenoma, advanced colorectal adenoma and CRC were 17.65% (6 302/35 714), 4.45% (1 589/35 714) and 3.71% (1 324/35 714), respectively. The overall detection rates of colorectal adenoma and advanced colorectal adenoma in the second 5 years were higher respectively than those in the first 5 years [20.33% (4 565/22 457) VS 13.10% (1 737/13 257), 4.69% (1 053/22 457) VS 4.04% (536/13 257)]. The overall detection rate of CRC in the second 5 years [3.30% (741/22 457)] was lower than that in the first 5 years [4.40% (583/13 257)].Conclusion:Compared with 2010 to 2014, the detection rate of colorectal adenoma in Shihezi area in 2015 to 2019 increased significantly, the detection rate of advanced colorectal adenoma increased slightly, and the detection rate of CRC decreased slightly. Therefore, the detection and resection of colorectal adenoma by colonoscopy may be important in reducing the incidence of CRC.