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.

Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lip-oprotein cholesterol(non-HDLC/HDLC)exposure on atherosclerotic cardiovascular disease(ASCVD).Methods A prospective cohort study was conducted.A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006-2007,2008-2009 and 2010-2011 were selected as the study subjects.Groups were divided into Q1,Q2,Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles.Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups,and Log-rank test was used to compare the differences among groups.Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD.Results The average follow-up was(10.19±2.21)years,and 5 003 new cases of ASCVD occurred.The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49％,8.71％,10.86％and 14.85％,respectively(Log-rank P＜0.01).Multivariate Cox regression analysis showed that compared with group Q1,the HR(95％CI)of ASCVD in groups Q2,Q3 and Q4 were 1.13(1.03～1.24),1.18(1.07～1.29),1.22(1.12～1.34),respectively;the HR(95％CI)of myocardial infarction were 1.15(0.87～1.53),1.44(1.10～1.88),1.67(1.29～2.17),respectively;the HR(95％CI)of revascularization were 1.21(0.99～1.49),1.31(1.07～1.60)and 1.49(1.22～1.81),respectively;the HR(95％CI)of ischemic stroke were 1.17(1.03～1.32),1.17(1.04～1.33)and 1.21(1.06～1.37),respectively;but the above association was not found when heart failure and atrial fibrillation were used as the outcome events.The restricted cubic spline showed that cumulative non-HDLC/HDLC values were line-arly associated with the risk of ASCVD.Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.

Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lip-oprotein cholesterol(non-HDLC/HDLC)exposure on atherosclerotic cardiovascular disease(ASCVD).Methods A prospective cohort study was conducted.A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006-2007,2008-2009 and 2010-2011 were selected as the study subjects.Groups were divided into Q1,Q2,Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles.Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups,and Log-rank test was used to compare the differences among groups.Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD.Results The average follow-up was(10.19±2.21)years,and 5 003 new cases of ASCVD occurred.The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49％,8.71％,10.86％and 14.85％,respectively(Log-rank P＜0.01).Multivariate Cox regression analysis showed that compared with group Q1,the HR(95％CI)of ASCVD in groups Q2,Q3 and Q4 were 1.13(1.03～1.24),1.18(1.07～1.29),1.22(1.12～1.34),respectively;the HR(95％CI)of myocardial infarction were 1.15(0.87～1.53),1.44(1.10～1.88),1.67(1.29～2.17),respectively;the HR(95％CI)of revascularization were 1.21(0.99～1.49),1.31(1.07～1.60)and 1.49(1.22～1.81),respectively;the HR(95％CI)of ischemic stroke were 1.17(1.03～1.32),1.17(1.04～1.33)and 1.21(1.06～1.37),respectively;but the above association was not found when heart failure and atrial fibrillation were used as the outcome events.The restricted cubic spline showed that cumulative non-HDLC/HDLC values were line-arly associated with the risk of ASCVD.Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.

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 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 study combined adjuvant transcatheter arterial chemoembolization (TACE) with anti-tumor drug treatment on early hepatocellular carcinoma (HCC) recurrence in patients with microvascular invasion (MVI) after partial hepatectomy with curative intent.Methods:The clinical and pathological data of 169 patients with HCC who underwent partial hepatectomy with curative intent from January 2015 to December 2018 at the Affiliated Hospital of Qingdao University were retrospectively analyzed. MVI was diagnosed by postoperative histopathology. There were 147 males and 22 females, with the median age 56 years(ranged 32-79 years). The patients were divided into surgery group ( n=62, patients who did not receive adjuvant therapy), TACE group ( n=42, patients who only received TACE) and combined group ( n=65, patients who received TACE with anti-tumor drug) according to the therapies after resection. Patients in each group were further divided into grade M1 (mild) and grade M2 (severe) subgroups according to the severity of MVI. All patients were followed-up for observing tumor recurrence. The relapse-free survival in the three groups were compared using the Kaplan-Meier method and the log-rank test was used to compare the tumor-free survival rates. Results:The tumor-free survival rates of 169 patients at 1 and 2 years after operation were 59.2% and 40.8%. The tumor-free survival rates at 1 and 2 years after operation were 45.2% and 25.8% in surgery group, 61.9% and 40.5% in TACE group, 70.8% and 52.3% in combined group respectively. The differences among the three groups were significant: TACE group was better than surgery group, and combined group was better than TACE group, combined group was better than surgery group (all P<0.05). In TACE group and combined group, tumor-free survival rates of M1patients better than M2 patients, and the difference was significant ( P<0.05). Among M1 patients and M2 patients, tumor-free survival rates of combined group patients were better than surgery group and TACE group, the difference was significant (all P<0.05). The cumulative tumor-free survival rate was not significantly affected by different antineoplastic agents. Conclusion:Adjuvant TACE reduced the early recurrence rate of HCC patients with MVI. Adjuvant TACE combined with anti-tumor drug further reduced early tumor recurrence.

Objective To determine the fetal facial angles at 11 －38 weeks of gestation by three‐dimensional ultrasound ( 3DUS) and analyze the correlation between facial angles and gestational age( GA ) . Methods From 2013 April to 2014 February ,439 singleton fetuses ranged 11－38 weeks of gestation were enrolled in this study . T he details of mid‐sagittal plane of facial profile was confirmed with 3DUS . Four facial angels were measured in this plane ,including frontomaxillary facial angle ( FM F ) ,frontonasal angle ( FNA ) ,mandibulomaxillary facial angle( M M F) and maxilla‐nasion‐mandible angle( M NM ) . T he intra‐and interobserver reliability were calculated in first 30 cases ,intra‐class correlation coefficient( ICC) greater than 0 .75 indicated good reliability . Pearson′s correlation coefficient ( r ) ,curve estimation and polynomial regression models were used to evaluate the correlation of the fetal facial angles with GA . Results ICC of the same observer were 0 .968 ,0 .962 ,0 .974 and 0 .988 ,respectively . ICC of different observer were 0 .948 , 0 .905 ,0 .874 and 0 .889 ,respectively . T he fetal facial angles of FM F ,FNA ,M M F and M NM showed correlations with GA ( r ＝ －0 .369 ,0 .447 ,－0 .470 ,0 .386 ; all P ＝0 .000) . Using GA as the independent variable and the facial angles as the dependent variables , the best fit regressing equation was cubic polynomial :FM F＝135 .300－6 .473×GA+0 .235×GA2 －0 .003×GA3 ( R2 ＝0 .240 , P ＝0 .000 ) ;FNA＝58 .920+7 .452×GA －0 .274×GA2 －0 .003×GA3 ( R2 ＝0 .297 , P ＝0 .000 ) ;M M F＝132 .329 －5 .337× GA+0 .191× GA2 －0 .002× GA3 ( R2 ＝ 0 .304 , P ＝ 0 .000) ;M NM ＝ －24 .592+ 4 .653× GA －0 .173× GA2 + 0 .002 × GA3 ( R2 ＝ 0 .413 , P ＝ 0 .000 ) . Conclusions The development of fetal facial angles are related to GA . T he growing patterns of fetal facial angles fit with a cubic polynomial function .

OBJECTIVE： To conduct sulfated modification of polysaccharide from Dictamnus dasycarpus （DDP-Ⅲ）， and to compare structure characteristics and anti-psoriasis activity of DDP-Ⅲ before and after sulfated modification. METHODS： DDP-Ⅲ was separated and purified with DEAE-52 anion exchange cellulose column and Sephadex G-100 column. After derived with 1-phenyl-3-methyl-5-pyrazolone， HPLC was used to determine the composition of its monosaccharide. SDDP-Ⅲ was synthesized using esterification reagent （anhydrous pyridine+chlorosulfonic acid） to modify DDP-Ⅲ. The degree of sulfate substitution was determined by barium chloride-gelatin turbidimetric method. The structures were compared by IR， Raman spectrum and SEM before and after modification. The male ICR mice were randomly divided into normal group， model group， positive group （tripterygium glycosides， 20 mg/kg） and DDP-Ⅲ/SDDP-Ⅲ low-dose， medium-dose and high-dose groups （56， 112， 224 mg/kg）. Except that normal group was given vaseline for external use， and other groups were given Imiquimod cream for external use to induce psoriasis model. At the same time， administration groups were given relevant medicine intragastrically 0.4 mL， and both normal group and model group were given constant volume of water intragastrically， once a day， for consecutive 14 d. Two hours after last medication， the serum contents of IL-17 and IL-23 were determined by ELISA. The skin scales near the tail were observed by HE staining， and the number of scales with granular layer was recorded. RESULTS： DDP-Ⅲ was composed of mannose， rhamnose， glucuronic acid， galacturonic acid and glucose. The degree of sulfate substitution was 0.65 for SDDP-Ⅲ. IR and Raman spectrum showed that the characteristic absorption peaks of sulfate radical group appeared near 1 255 cm－1 and 823 cm－1， 1 240 cm－1 and 815 cm－1 for SDDP-Ⅲ， except for same characteristic absorption peak as DDP-Ⅲ. SEM analysis showed that DDP-Ⅲ was flaky， smooth and tightly arranged； SDDP-Ⅲ was massive or granular with porous structure and loose arrangement. Animal experiment showed that compared with normal group， the epidermis of skin lesion was significantly thickened and the granular layer was significantly reduced； serum contents of IL-17 and IL-23 were increased significantly， while the number of scales with granular layer was decreased significantly （P＜0.05 or P＜0.01）. Compared with model group， above symptoms of administration groups were improved to different extent， and serum contents of IL-17 and IL-23 in positive group， DDP-Ⅲ high-dose groups， SDDP-Ⅲ medium-dose and high-dose groups were decreased significantly； the number of scales with granular layer was increased significantly， and above indexes of SDDP-Ⅲ medium-dose and high-dose groups were significantly better than corresponding DDP-Ⅲ group （P＜0.05 or P＜0.01）. CONCLUSIONS： DDP-Ⅲ contains five monosaccharide components such as mannose， etc. Both DDP-Ⅲ and SDDP-Ⅲ possess anti- psoriasis effects， and SDDP-Ⅲ exhibits stronger anti-psoriasis effect than DDP-Ⅲ. Its mechanism may be associated with inhibiting IL-23/IL-17 signaling pathway.

Objective To explore the application value of ultrasound medical imaging workstation in quality control of ultrasound reports issued by resident doctors.Methods The pancreatic ultrasound reports of outpatients provided by resident doctors with 6 months and 12 months of training were derived from the ultrasound medical imaging workstation as 6-month group (G6M) and 12-month group (G12M),respectively.There were 1582 ultrasound reports in the G6M,including 420 for males and 962 for females,with 1318 for patients ＜ 65 years old and 264 for patients ≥ 65 years old.There were 2723 ultrasound reports in the G12M,including for 760 males and 1963 for females,with 2323 for patients ＜ 65 years old and 400 for patients ≥ 65 years old.Frequency of"unclear tail of the pancreas" in the report,standard image,and body markers were recorded.The chi-square test was used to compare patient gender,age,and the quality of resident reports between the two groups.Results The chi-square test showed that there was no significant difference in sex or age composition between the two groups (all P ＞ 0.05).The number of cases of"unclear tail of the pancreas" reported in the G6M and G12M was 554 (35.02％) and 734 (26.96％),respectively,and there was a statistical difference between the two groups (x2=31.029,P ＜ 0.001).In the reports with "unclear tail of the pancreas",the number of reports with "no map" was 8 (1.44％) and 14 (1.91％) in the G6M and G12M,respectively,and there was no significant difference between the two groups (P ＞ 0.05).As to "map without marker" and "map with marker",there were 337 (60.83％) vs 209 (37.73％) and 308 (41.96％) vs 412 (56.13％) in the G6M and G12M,respectively,and the chi-square test showed that there were significant differences between the two groups (x2=44.960 and 42.834,all P ＜ 0.001).Conclusion Ultrasound medical imaging workstation can be used for periodic spot check,evaluation,and feedback of resident reports,which has a positive role in promoting the quality control of ultrasound reports.

Objective: To explore the value of prenatal ultrasound in diagnosis of congenital dacryocystocele. Methods: The ultrasonographic features of 16 fetuses with congenital dacryocystocele were retrospectively reviewed and the outcome of pregnancy were followed up. Results: The median gestational week detected with prenatal ultrasound was 30.29 weeks, the mean diameter was (8.96±1.96)mm. Congenital dacryocystoceles were unilateral in 12 fetuses and bilateral in 4 fetuses, 10 were female and 6 were male. The typical ultrasonic feature was anechoic cystic mass with clear boundary in relation to the medial and inferior aspects of the fetal orbit. The dacryocystocele resolved spontaneously prenatally in 5 fetuses, resolved spontaneously after delivery in 10 fetuses. One fetus died in caesarean section due to complete placenta previa. Conclusions Congenital dacryocystitis has its characteristic ultrasonographic features, and most cases can disappear naturally in prenatal or early newborns.