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 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 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.

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.

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 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.

Objective We aimed to compared matrix metalloproteinase-13 (MMP-13) and transforming growth factor-β1 (TGF-β1) in synovial fluid,the phosphorylation level of Smad3 in articular cartilage (P-Smad3),and their correlation with traditional Chinese medicine (TCM) patterns in patients with knee osteoarthritis (KOA) of liver-kidney deficiency pattern and pattern of intermingled phlegm and blood stasis.Methods Using a cross-sectional field investigation method,KOA patients hospitalized in the Orthopedics Department of Dongzhimen Hospital,Beijing University of Chinese Medicine from September 2019 to February 2023 were collected. A total of 112 KOA patients were included,among which 63 cases were diagnosed with liver-kidney deficiency pattern,and 49 cases were diagnosed with pattern of intermingled phlegm and blood stasis. The intensity of knee pain,function,and X-ray imaging result were quantified using the Visual Analogue Scale (VAS),Lysholm Knee Scoring Scale,and Kellgren-Lawrence (K-L) Grading Scale,respectively. The TCM pattern was identified and quantified using a TCM Pattern Scoring Scale. Immunohistochemistry was used to determine the phosphorylation characteristics of Smad3 in articular cartilage,and ELISA was used to measure the contents of MMP-13 and TGF-β1 in synovial fluid. The level characteristics and their correlation with the degree of syndrome were analyzed.Results (i) There was no statistically significant difference in VAS scores,Lysholm scores,and K-L grades between KOA patients with different TCM patterns. (ii) Compared with KOA patients with pattern of intermingled phlegm and blood stasis,patients with pattern of liver-kidney deficiency had higher levels of MMP-13 in synovial fluid and lower levels of TGF-β1 in synovial fluid (P<0.05). (iii) In KOA patients with liver-kidney deficiency pattern,there was a positive correlation between the level of MMP-13 in synovial fluid and the score of TCM pattern (r=0.292,P=0.020),while there was a negative correlation between the level of TGF-β1 in synovial fluid and the score of TCM pattern (r=-0.781,P<0.001). In KOA patients with pattern of intermingled phlegm and blood stasis,there was also a positive correlation between the level of MMP-13 in synovial fluid and the score of TCM pattern (r=0.936,P<0.001). (iv) The mean optical density value of P-Smad3 in articular cartilage was lower in KOA patients with liver-kidney deficiency pattern than in pattern of intermingled phlegm and blood stasis (P<0.05).Conclusion KOA patients with liver-kidney deficiency pattern or pattern of intermingled phlegm and blood stasis have different levels of TGF-β1 and MMP-13 in synovial fluid,as well as varying degrees of Smad3 phosphorylation in articular cartilage,which is consistent with the analysis of etiology and pathogenesis under different patterns. The levels of TGF-β1 and MMP-13 in synovial fluid of patients with liver-kidney deficiency pattern can reflect the severity of the pattern to a certain extent,and the mechanism may be related to the inhibition of the activation level of the TGF-β/Smad signaling pathway. This study enriches the research content of the material basis of TCM patterns.

Objective:To analyze the blood differential metabolites of patients with intrahepatic cholestasis (IHC) by liquid chromatography-mass spectrometry metabolomics technology so as to find potential metabolic target.Method:Serum samples were collected from thirty patients with intrahepatic cholestasis and thirty healthy individuals after metabolomics analysis. The differential metabolites were initially screened based on the multiple differences and significance. KEGG enrichment analysis was performed on the differential metabolites to determine the candidate targets. The potential clinical application value of these characteristic metabolites was analyzed using the receiver operating characteristic curve.Result:A total of thirty patients with intrahepatic cholestasis and thirty healthy adults were included. The age difference between the two groups was not statistically significant ( P>0.05). The clinical condition was consistent with the statistically significant differences in liver biochemical indicators, blood routine, coagulation, and inflammatory indicators between the two groups ( P<0.05). Furthermore, a blood metabolomics screening analysis revealed 99 differentially expressed metabolites associated with intrahepatic cholestasis. Of these, 15 showed statistically significant differences. Glucose, lipid, and energy metabolisms were the various primary types of differential metabolites involved. The receiver operating characteristic curve>0.9 included the following twelve kinds of metabolites: 1H-indole-3-carboxaldehyde, 6-hydroxy-1H-indole-3-acetamide, phenylalanyl tryptophan, 1-methylguanosine, 2-ethoxy-5-methylpyrazine, p-hydroxybenzaldehyde, 5-(2-chlorophenyl)-3,4-dihydro-2H-pyrrole, methylthioadenosine, alanylisoleucine, anabsinthin, N-acetyl-DL-histidine monohydrate, N-methylnicotinamide, and others. The fifteen metabolites that were previously identified and calculated according to the differential quantitative value of the metabolite corresponding ratio exhibited fold-changes in the upregulated and downregulated potential biomarkers (phenylalanine tryptophan, phenylalanine, 5'-methylthioadenosine, anabsinthin, and N-methylnicotinamide) in combination with the area under the receiver operating characteristic curve>0.9. Conclusion:Phenylalanyl tryptophan, phenylalanylalanine, 5'-methylthioadenosine, anabsinthin, and N-methylnicotinamide may serve as potential metabolic markers to distinguish patients with cholestasis from healthy controls. N-methylnicotinamide, among them, is of great importance as a potential marker.