Objective: To investigate the characteristics and HIV confirmed positive status among individuals attending HIV voluntary counseling and testing (VCT) clinics in Inner Mongolia Autonomous Region, so as to provide the basis for enhancing interventions targeting high-risk populations for AIDS. Methods: Demographic information, reasons for consultation, consulting institutions, and HIV antibody testing data of individuals attending VCT clinics in Inner Mongolia Autonomous Region from 2019 to 2023 were collected through the VCT database of the Chinese Center for Disease Control and Prevention. The characteristics of individuals attending VCT were described. Factors affecting HIV confirmed positive among VCT clinic attendees were analyzed using a multivariable logistic regression model. Results: A total of 249 919 individuals attended VCT clinics in Inner Mongolia Autonomous Region from 2019 to 2023, including 128 069 males (51.24%) and 121 850 females (48.76%). The majority of attendees were aged 25-<35 years, accounting for 92 445 cases (36.99%). Among them, 785 cases were confirmed as HIV positive, with a positivity rate of 0.31%. Multivariable logistic regression analysis revealed that males (OR=4.787, 95%CI: 3.562-6.434), 45-<65 years of age (45-<55 years, OR=7.723, 95%CI: 1.786-33.406; 55-<65 years, OR=7.689, 95%CI: 1.757-33.653), being unmarried (OR=2.143, 95%CI: 1.580-2.906), junior high school education or below (OR=1.147, 95%CI: 1.042-2.430), having the history of high-risk behaviors or exposure risks (commercial heterosexual behaviors, OR=2.717, 95%CI: 1.707-4.324; non-commercial non-fixed heterosexual behaviors, OR=5.421, 95%CI: 3.763-7.809; homosexual behaviors, OR=70.774, 95%CI: 48.409-103.473; having an HIV-positive spouse/fixed partner/mother, OR=100.024, 95%CI: 62.490-160.100; drug injection, OR=5.366, 95%CI: 2.213-13.014), and seeking general hospitals or traditional Chinese medicine hospitals (OR=1.973, 95%CI: 1.650-2.360) were associated with a higher risk of HIV confirmed positive. Conclusions HIV confirmed positive among individuals attending VCT clinics in Inner Mongolia Autonomous Region is associated with gender, age, marital status, educational level, reasons for consultation, and consulting institutions. It is recommended to strengthen health education and targeted interventions for high-risk populations to reduce the risk of HIV infection.

Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.

Cholesterol(CH)plays a crucial role in enhancing the membrane stability of drug delivery systems(DDS).However,its association with conditions such as hyperlipidemia often leads to criticism,overshadowing its influence on the biological effects of formulations.In this study,we reevaluated the delivery effect of CH using widely applied lipid microspheres(LM)as a model DDS.We conducted comprehensive in-vestigations into the impact of CH on the distribution,cell uptake,and protein corona(PC)of LM at sites of cardiovascular inflammatory injury.The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage.Then,the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy.Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma(PPAR-γ)expression in vascular endothelial cells and estrogen receptor alpha(ERα)protein levels in myocardial cells,thereby enhancing LM uptake at cardiovascular inflam-mation sites.Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V(Apoa5);this may be a major contributing factor to their prolonged circu-lation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites.It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations.The findings enhance the conceptualization of CH and LM delivery,providing novel strategies for investigating prescription factors' bioactivity.

Objective To investigate the CT and MRI features of giant cell reparative granuloma(GCRG)in lateral skull base.Methods The CT,MRI and clinicopathological data of 8 patients with GCRG in lateral skull base were collected and analyzed.Results All of the eight lesions were unilateral and solitary(three on the left side and five on the right side),with widespread involvement affecting two or more bony structures of the lateral skull base.All lesions showed expansile and lytic bone destruction on CT scans,the margins were clear(7/8),and the sclerotic changes could be seen at the margin of all eight lesions.On MRI,the lesions revealed heterogeneous isointense and hypointense on T1WI,and heterogeneous hypointense with focal cystic changes on T2WI,without fluid-fluid levels.The enhanced scan showed heterogeneous enhancement.Seven cases extended to the middle cranial fossa,caused com-pression of the temporal lobe brain tissue,with thickened and strengthened adjacent meninges.Conclusion The GCRG in lateral skull base has certain characteristic appearances on CT and MRI;understanding these characteristic manifestations can provide a basis for accurate diagnosis.

Objective To investigate the causal relationship between frailty and epilepsy based on the traditional Chinese medicine(TCM)theory of"epilepsy caused by frailty"utilizing a two-sample Mendelian randomization approach,to enrich the modern connota-tion of the"epilepsy caused by frailty"theory and provide a theoretical basis for treating epilepsy from a frailty perspective in TCM.Methods Data on frailty and epilepsy were extracted from publicly available genome-wide association study summary datasets.Single nucleotide polymorphism(SNP)were selected as instrumental variable under the conditions of P＜5 x 10-8,a linkage disequilibrium co-efficient of 0.001,and a linkage disequilibrium region width of 10000kb.Mendelian randomization analysis was performed using five methods:MR-Egger regression,weighted median,inverse variance weighting,simple mode and weighted mode,with inverse variance weighting as the primary analysis method.The causal relationship between frailty and epilepsy was interpreted using OR and 95％CI.Pleiotropy was assessed using the MR-Egger intercept and MR-PRESSO analysis methods,while heterogeneity was analyzed using MR-Egger Cochran's Q test,and sensitivity analysis was conducted using the leave-one-out method.Results The results of inverse variance weighting and weighted median analysis indicated that there was a positive causal relationship between frailty and epilepsy.This result passed pleiotropy tests,confirming its robustness.Conclusion Frailty is associated with an increased risk of epilepsy,which is consistent with the TCM understanding of"epilepsy caused by frailty".It is suggested that in clinical treatment,besides conventional ap-proaches such as resolving phlegm,eliminating blood stasis,calming wind,and opening orifices,there should be a greater emphasis on tonifying frailty and nurturing the body's vital energy.

Objective To investigate the CT and MRI features of giant cell reparative granuloma(GCRG)in lateral skull base.Methods The CT,MRI and clinicopathological data of 8 patients with GCRG in lateral skull base were collected and analyzed.Results All of the eight lesions were unilateral and solitary(three on the left side and five on the right side),with widespread involvement affecting two or more bony structures of the lateral skull base.All lesions showed expansile and lytic bone destruction on CT scans,the margins were clear(7/8),and the sclerotic changes could be seen at the margin of all eight lesions.On MRI,the lesions revealed heterogeneous isointense and hypointense on T1WI,and heterogeneous hypointense with focal cystic changes on T2WI,without fluid-fluid levels.The enhanced scan showed heterogeneous enhancement.Seven cases extended to the middle cranial fossa,caused com-pression of the temporal lobe brain tissue,with thickened and strengthened adjacent meninges.Conclusion The GCRG in lateral skull base has certain characteristic appearances on CT and MRI;understanding these characteristic manifestations can provide a basis for accurate diagnosis.

Objective To investigate the causal relationship between frailty and epilepsy based on the traditional Chinese medicine(TCM)theory of"epilepsy caused by frailty"utilizing a two-sample Mendelian randomization approach,to enrich the modern connota-tion of the"epilepsy caused by frailty"theory and provide a theoretical basis for treating epilepsy from a frailty perspective in TCM.Methods Data on frailty and epilepsy were extracted from publicly available genome-wide association study summary datasets.Single nucleotide polymorphism(SNP)were selected as instrumental variable under the conditions of P＜5 x 10-8,a linkage disequilibrium co-efficient of 0.001,and a linkage disequilibrium region width of 10000kb.Mendelian randomization analysis was performed using five methods:MR-Egger regression,weighted median,inverse variance weighting,simple mode and weighted mode,with inverse variance weighting as the primary analysis method.The causal relationship between frailty and epilepsy was interpreted using OR and 95％CI.Pleiotropy was assessed using the MR-Egger intercept and MR-PRESSO analysis methods,while heterogeneity was analyzed using MR-Egger Cochran's Q test,and sensitivity analysis was conducted using the leave-one-out method.Results The results of inverse variance weighting and weighted median analysis indicated that there was a positive causal relationship between frailty and epilepsy.This result passed pleiotropy tests,confirming its robustness.Conclusion Frailty is associated with an increased risk of epilepsy,which is consistent with the TCM understanding of"epilepsy caused by frailty".It is suggested that in clinical treatment,besides conventional ap-proaches such as resolving phlegm,eliminating blood stasis,calming wind,and opening orifices,there should be a greater emphasis on tonifying frailty and nurturing the body's vital energy.

ObjectiveTo evaluate some properties of scutellarin-phospholipid complex nanoemulsion（SCU-PC-NE）， such as release， cell uptake and tissue distribution， and to investigate its effect on ameliorating lipopolysaccharide（LPS）-induced vascular endothelial injury. MethodSCU-PC-NE was prepared by weighting SCU-PC， ethyl oleate， Kolliphor HS15， 1，2-propylene glycol（50， 400， 514.3， 85.7 mg）， respectively. And the appearance of SCU-PC-NE was observed by transmission electron microscope， the average paticle size and Zeta potential were measured by nanopotential particle size analyzer. The cumulative release of SCU-PC-NE in vitro was measured by dynamic dialysis， thiazolyl blue（MTT） colorimetric assay was used to investigate the effect of SCU-PC-NE on the viability of human umbilical vein endothelial cells（HUVECs）， the inverted fluorescence microscope and flow cytometry were used to investigate cell uptake of HUVECs by SCU-PC-NE in vitro using coumarin 6 as a fluorescent probe， the tissue distribution of DiR/SCU-PC-NE labeled by near infrared fluorescent dyes was obeserved by small animal in vivo imaging system. The inflammation injury model was established by co-incubation with LPS（1 mg·L^-1） and HUVECs， the effect of SCU-PC-NE on the levels of interleukin（IL）-1β and IL-6 were determined by enzyme-linked immunosorbent assay（ELISA）， 18 Kunming male mice were randomly divided into blank group， model group， blank preparation group（equivalent to high dose group）， SCU group and SCU-PC-NE low and high dose groups（5， 10 mg·kg^-1）， 3 mice in each group， and the drug administration groups were administered once in the tail vein at the corresponding dose every 48 h， equal volume of normal saline was given to the blank group and the model group， and the drug was administered for 4 consecutive times. Except for the blank group， the endothelial inflammatory injury was induced by intraperitoneal injection of LPS（10 mg·kg^-1） at 12 h before the last administration in each group. Hematoxylin-eosin（HE） staining was used to investigate the effect of SCU-PC-NE on the histopathological changes in the thoracic aorta of mice. ResultThe appearance of SCU-PC-NE displayed pale yellow milky light， mostly spherical with rounded appearance and relatively uniform particle size distribution， with the average particle size of 35.31 nm， Zeta potential of 7.23 mV， and the encapsulation efficiency of 75.24%. The cumulative release in vitro showed that SCU-PC-NE exhibited sustained release properties compared with SCU. The cell viability of SCU-PC-NE was >90% at a concentration range of 1.05-8.4 mg·L^-1. The results of cellular uptake experiments showed that the cellular uptake ability of SCU-PC-NE was significantly enhanced when compared with the SCU group（P<0.01）. Compared with normal mice， the results of tissue distribution showed that the fluorescence intensity of DiR/SCU-PC-NE was significantly enhanced in the spleen， kidney， brain and thoracic aorta of mice at different time points after intraperitoneal injection of LPS（P<0.05， P<0.01）， especially in thoracic aorta. ELISA results showed that the levels of IL-1β and IL-6 in the model group were significantly increased when compared with the blank group（P<0.05， P<0.01）， and compare with the model group， all administration groups significantly down-regulated IL-1β level， with the strongest effect in the SCU-PC-NE high-dose group（P<0.01）， and all administration groups significantly down-regulated IL-6 level， with the strongest effect in the SCU-PC-NE low-dose group（P<0.05）. Compare with the blank group， the results of HE staining showed that the endothelial cells were damaged， the elastic fibers were broken and arranged loosely in the model group， although similar vascular injury could be observed in the blank preparation group， SCU group and SCU-PC-NE low-dose group， the vascular endothelial damage was significantly reduced in the high-dose group of SCU-PC-NE， which had a better effect than that in the SCU group. ConclusionSCU-PC-NE can promote the uptake of drugs by endothelial cells and effectively enriched in the site of vascular endothelial injury caused by LPS， suggesting that it has a protective effect on vascular endothelial injury and is a good carrier of SCU.

OBJECTIVE To study the interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes. METHODS In vitro ferroptosis model was established in pancreatic β cells of mice by using high glucose. The effects of low-dose and high-dose 1，8-cineole （0.25， 0.5 μmol/L） on the level of Fe2+ in pancreatic β cells were investigated. The effects of 1，8-cineole （0.5 μmol/L） combined with ferroptosis inducer Erastin （20 μmol/L） and ferroptosis inhibitor Ferrostatin-1 （20 μmol/L） on the protein expressions of glutathione peroxidase-4 （GPX4） and cyclooxygenase-2 （COX2） were also detected. The type 2 diabetes model mice were established by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The effects of low-dose and high-dose 1，8-cineole （50， 200 mg/kg） on the pathological morphology of pancreatic tissue， the content of iron as well as the protein expressions of GPX4 and COX2 were investigated. RESULTS The results of the cell experiment showed that compared with the model group， pretreatment with 1，8-cineole significantly reduced intracellular Fe2+ levels and upregulated GPX4 protein expression， while downregulated COX2 protein expression in pancreatic β cells （P＜0.05）. After combining with Ferrostatin-1， the expression trends of the above two proteins were the same， while there was no statistically significant difference after combining with Erastin. The results of animal experiments showed that compared with the model group， after intervention with 1，8-cineole， the structure of the pancreatic islets in mice recovered intact and their morphology improved； the iron content of pancreatic tissue and protein expression of COX2 were decreased significantly （P＜0.05）， while protein expression of GPX4 was increased significantly （P＜0.05）. CONCLUSIONS 1，8-cineole could ameliorate pancreatic β cell injury induced by diabetes， the mechanism of which may be related to reducing intracellular iron deposition and regulating ferroptosis-related proteins.

Objective:To explore the genetic basis for a fetus with Cardiac valvular dysplasia type 1 (CVDP1).Methods:A CVDP1 fetus identified at the Ningbo Women and Children′s Hospital on July 7, 2022 was selected as the study subject. Clinical data of the fetus was collected. The fetus and its parents were subjected to trio-whole exome sequencing (trio-WES), and candidate variants were verified by Sanger sequencing.Results:The fetus had exhibited generalized edema, complex cardiac malformation, abdominal effusion, and enhanced intestinal and renal parenchymal echoes. Trio-WES revealed that it has harbored compound heterozygous variants of the PLD1 gene, namely c. 2977C>T (p.R993*) and c. 1460G>A (p.W487*), which were respectively inherited from its father and mother. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 2977C>T (p.R993*) variant was evaluated to be likely pathogenic (PVS1_Moderate+ PM2_Supporting+ PM3+ PP4), whilst the c. 1460G>A (p.W487*) variant was evaluated to be pathogenic (PVS1+ PM2_Supporting+ PP4). Conclusion:The c. 2977C>T (p.R993*) and c. 1460G>A (p.W487*) compound heterozygous variants of the PLD1 gene probably underlay the CVDP1 in the fetus. Above discovery has enriched the mutational spectrum of the PLD1 gene and provided a guidance for genetic counseling and prenatal diagnosis in this family.