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 explore whether inhaling Bingchangsan(BCS can modulate the Nrf2/HO-1 signaling pathway to improve ferroptosis and cognitive dysfunction in Alzheimer's Disease(AD mouse models.METHODS 30 APP/PS1 mice were ran-domly divided into three groups:a model group(APP/PS1 group,a low-dose Bingchangsan group(BCS-L group,and a high-dose Bingchangsan group(BCS-H group.10 age-matched wild-type(WT mice were used as a control group.The WT group and the APP/PS1 group were treated with nebulized pure water,while the BCS-L group received 0.5μL of Bingchangsan inhalation solution per day,and the BCS-H group received 1μL,both administered via nebulization for 10 min daily for 2 weeks.2 weeks post-treat-ment,spatial cognitive abilities of the mice were assessed using the Morris water maze test.Following the water maze experiment,the mice were euthanized,and their brain tissues were collected for Aβ1-42 immunofluorescence,P-tau immunohistochemistry,and Nissl staining.Hippocampal tissues were extracted for Western blot and qPCR analysis to measure the protein and mRNA expression levels of Keap1,Nrf2,HO-1,GPX4,SCL7A11,TFRC,DMT1,FTL,and FTH1.Additionally,brain tissues were used for glutathione(GSH content measurement using a GSH assay kit.RESULTS In the BCS groups,the latency period for escape shortened,and the time spent in the quadrant with the platform,as well as the number of times crossing the platform,increased.Compared to the APP/PS1 group,the expression levels of Aβ1-42 and P-tau in the hippocampal CA1 region and cortex of mice in the BCS groups were signifi-cantly reduced(P<0.05,P<0.01.Nissl staining revealed a denser arrangement of neurons with more Nissl bodies in the BCS groups.In the hippocampal tissue,compared to untreated APP/PS1 mice,significant increases in the protein and mRNA levels of Nrf2,HO-1,SLC7A11,GPX4,and FTL were observed in all BCS groups(P<0.05,P<0.01.While the BCS-L group showed in-creased levels of FTH1 protein and mRNA,these changes were not statistically significant.Furthermore,the expression levels of TFRC,DMT1,and Keap1 were significantly downregulated in the BCS groups(P<0.05,P<0.01.Additionally,treatment with BCS effectively restored the glutathione(GSH content in the brain(P<0.01.CONCLUSION Inhalation of BCS can improve cognitive dysfunction in APP/PS1 mice.BCS activates the Nrf2/HO-1 pathway,increases the expression of GPX4,and enhances Nrf2 tran-scriptional activity by inhibiting Keap1.This leads to an upregulation of SLC7A11 and restoration of GSH levels,effectively countering ferroptosis.Additionally,BCS effectively inhibits TFRC and DMT1,while upregulating FTL and FTH1 expression,thereby maintaining intracellular iron homeostasis.This contributes to mitigating the impact of ferroptosis on APP/PS1 mice,subsequently enhancing their cognitive functions.

Objective:To determine incidence of seasonal influenza virus infection in the community and to analyze the factors influencing seasonal influenza virus infection.Methods:This study recruited residents aged 6-59 years to build a cohort in 15 villages/streets in Macheng city in November 2019. Meanwhile, a cross-sectional baseline survey was conducted immediately to collect sera, information on demographics and child protection knowledge, behaviors, as well as attitudes using a questionnaire from the participants enrolled in the cohort (i.e., before the influenza epidemic season). In July 2020, a cross-sectional follow-up survey was conducted to collect sera once again (i.e., after the influenza season). Paired sera from the two cross-sectional surveys were tested for influenza virus-specific antibodies by hemagglutination inhibition (HI) test or micro-neutralization (MN) test using a circulating representative strain of each subtype/lineage of influenza virus as the test antigen. The infections with influenza virus subtype/lineage was confirmed if there was a four-fold or more increase in titers of antibodies against circulating representative strain of the subtype/lineage of influenza virus. Factors influencing infection with influenza A (H3N2) and B/Victoria viruses were analyzed using univariable and multivariable logistic regression.Results:In November 2019, 800 study participants were enrolled in the cohort, including 340 children aged 6-17 years and 460 adults aged 18-59 years; 605 study participants (including 224 children and 381 adults) were followed up in July 2020 and their paired sera were obtained before and after the influenza season. 25.3% (153/605) of the participants were confirmed to be infected with at least one subtype/lineage of seasonal influenza virus by HI and MN tests. The overall incidence of influenza viruses of all subtypes/lineages in children was 44.2% (95% CI: 37.6%-50.8%) which was significantly higher than the incidence of 14.1% in adults (95% CI: 10.7%-17.7%). Children had the highest incidence of influenza A (H3N2) virus infection, followed by B/Victoria. MN or HI antibody titers in A (H3N2)[ OR=0.88 (95% CI: 0.84-0.93)] and B/Victoria[ OR=0.97 (95% CI: 0.95-0.99)] before the influenza season were significantly associated with whether children were infected with that subtype/lineage of influenza virus. Conclusions:The residents aged 6-59 years in Macheng city had a substantial incidence of seasonal influenza virus infection during the influenza season from winter 2019 to spring 2020. Notably, almost half of children aged 6-17 years have been infected with seasonal influenza virus. Higher titers of HI/MN antibodies against seasonal influenza virus before the influenza season would be likely to reduce the risk of infection with influenza A (H3N2) and B/Victoria.

Objective To observe the value of whole-tumor apparent diffusion coefficient(ADC)histogram for identifying histopathological grade of alveolar soft part sarcoma(ASPS).Methods Forty-three ASPS patients,including 27 cases of high-grade ASPS(high-grade group)and 16 cases of low-grade ASPS(low-grade group)were retrospectively enrolled.Patients'survival data were collected,MRI manifestations of ASPS were recorded,and the whole-tumor ADC histogram parameters were obtained and compared between groups.The correlations of whole-tumor ADC histogram parameters being different between groups with tumors'histological grading were analyzed,and the efficacy of whole-tumor ADC histogram parameters for identifying high-grade and low-grade ASPS were assessed.Results The 5-year survival rate of ASPS patients in low-grade group was 82.05％,higher than that(51.28％)in high-grade group(P＜0.05).The percentage of distant metastasis,tumor≥5 cm,as well as of tumors with features such as peritumoral edema and intra-tumoral septum in high-grade group were all higher than in low-grade group(all P＜0.05).The 5th,10th,25th,50th,75th,90th and the mean values of ADC in high-grade group were all lower than those in low-grade group(all P＜0.05)and negatively correlated with pathohistological grade of ASPS(from-0.547 to-0.385,all P＜0.05).The aeras under the receiver operating characteristic curves of the above parameters ranged from 0.734 to 0.822,which were fairly good for identifying high-grade and low-grade ASPS.Conclusion Whole-tumor ADC histogram parameters could be used to effectively identify high-grade and low-grade ASPS.

Objective To investigate the effect of Piezo1 activated by mechanical stress on knee osteoarthritis synovial fibrosis via the extracellular signal-regulated kinase(ERK)1/2 signaling pathway.Methods Twenty-five Sprague Dawley rats were divided into blank,exercise,exercise+GsMTx4,exercise+PD98059,and exercise+GsMTx4+PD98059 groups(n=5 per group).After modeling,serum and synovial tissue were extracted and collagen deposition was evaluated by Sirius red and Masson staining.Expression levels of Piezo1,ERK1/2,phospho(p)-ERK1/2,α-smooth muscle actin(SMA),transforming growth factor(TGF)-β,Collagen Ⅰ,and tissue inhibitor of metalloproteinase(TIMP)-1 were detected by Western blot and reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and the interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α contents were detected by enzyme-linked immunosorbent assay.For cell experiments,synovial cells were divided into blank,pull,pull+GsMTx4,pull+PD98059,and pull+GsMTx4+PD98059 groups and the above indices were detected in the model cells by Western blot,RT-qPCR,and other techniques.Results Mechanical stress increased collagen deposition in synovial tissues in the rats,and increased the protein and mRNA expression levels of the pathway-related and fibrosis-specific indicators Piezo1,p-ERK/ERK,α-SMA,TGF-β,Collagen I,and TIMP-1(P＜0.05).Piezo1 expression was significantly down-regulated by both inhibitors(P＜0.05),but the ERK inhibitor(PD98059)had no significant effect on Piezo1 gene expression.Levels of serum inflammatory factors were significantly higher in the exercise group compared with the blank group(P＜0.05),and levels were significantly reduced by the inhibitors(P＜0.05).The in vitro experiments showed the same trends as the animal experiments.Conclusions The Piezo1 ion channel can sense mechanical stress and activate the ERK 1/2 pathway to mediate knee synovial fibrosis.

Intrahepatic cholangiocarcinoma is a highly aggressive type of liver cancer, and traditional hepatectomy has shown limited efficacy. Recently, liver transplantation has garnered attention as a potential therapeutic option. The criteria for selecting patients for liver transplantation have been a focal point of research. For early-stage patients, liver transplantation can offer favorable survival rates; however, for those with advanced or locally advanced cases that are not amenable to conventional resection, the efficacy of liver transplantation remains to be further validated. Given the scarcity of donors, living donor liver transplantation and extended criteria donor liver transplantation are gradually being applied to patients with intrahepatic cholangiocarcinoma. Additionally, the advent of adjuvant and neoadjuvant therapies has brought hope to some advanced or conventionally unresectable intrahepatic cholangiocarcinoma patients who undergo liver transplantation. Particularly, the use of immune checkpoint inhibitors may serve as a bridging or adjunct therapy for liver transplantation in the future. The development and exploration of autologous and xenogeneic liver transplantation have introduced new perspectives. This paper provides a review of the current status and progress of liver transplantation in the treatment of intrahepatic cholangiocarcinoma based on relevant literature.

Objective:To predict the short-term postoperative recurrence status of patients with refractory temporal lobe epilepsy (TLE) by analyzing preoperative 18F-FDG PET images and patients′ clinical characteristics based on deep residual neural network (ResNet). Methods:Retrospective analysis was conducted on preoperative 18F-FDG PET images and clinical data of 220 patients with refractory TLE (132 males and 88 females, age 23.0(20.0, 30.2) years)) in the First Affiliated Hospital of Jinan University between January 2014 and June 2020. ResNet was used to perform high-throughput feature extraction on preprocessed PET images and clinical features, and to perform a postoperative recurrence prediction task for differentiating patients with TLE. The predictive performance of ResNet model was evaluated by ROC curve analysis, and the AUC was compared with that of classical Cox proportional risk model using Delong test. Results:Based on PET images combined with clinical feature training, AUCs of the ResNet in predicting 12-, 24-, and 36-month postoperative recurrence were 0.895±0.073, 0.861±0.058 and 0.754±0.111, respectively, which were 0.717±0.093, 0.697±0.081 and 0.645±0.087 for Cox proportional hazards model respectively ( z values: -3.00, -2.98, -1.09, P values: 0.011, 0.018, 0.310). The ResNet showed best predictive effect for recurrence events within 12 months after surgery. Conclusion:The ResNet model is expected to be used in clinical practice for postoperative follow-up of patients with TLE, helping for risk stratification and individualized management of postoperative patients.

Objective: To establish a reliable and sensitive method for evaluating quality of Yiqi Jiangzhi Granules (YQJZG). Methods: Ultra performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) was employed for simultaneous determination of eight marker components. Separation was performed on an AQUITY UPLC® HSS T3 column, the mobile phase consisted of acetonitrile as the organic phase and 0.1% (volume percentage) formic acid as the aqueous. Eight marker components, ginsenoside Rg1 (GRg1), ginsenoside Re (GRe), ginsenoside Rb1 (Gb1), typhaneoside (TEO), isorhamnetin-3-O-neohespeidoside (IN), hesperidin (HPD), aurantio-obtusin-6-O-β-D-glucoside (AG) and curcumin (CCM), were detected by multiple reaction monitoring (MRM) mode. The Chinese Pharmacopoeia (2020 edition) was regarded as the guidance document for this method validation. Results: The method showed good linearity (R

Objective    To analyze the expression and clinical significance of cyclin-dependent kinase 1 (CDK1) in lung adenocarcinoma by bioinformatics. Methods    Based on the gene expression data of lung adenocarcinoma patients in The Cancer Genome Atlas (TCGA), the differential expression of CDK1 in lung adenocarcinoma tissues and normal lung tissues was analyzed. The expression of CDK1 gene in lung adenocarcinoma was analyzed by UALCAN at different angles. Survival analysis of different levels of CDK1 gene expression in lung adenocarcinoma was performed using Kaplan-Meier Plotter. Correlation Cox analysis of CDK1 expression and overall survival was based on clinical data of lung adenocarcinoma in TCGA. Gene set enrichment analysis was performed on gene sequences related to CDK1 expression in clinical cases. The protein interaction network of CDK1 from Homo sapiens was obtained by STRING. CDK1-related gene proteins were obtained and analyzed by the web server Gene Expression Profiling Interactive Analysis (GEPIA). Results    Based on the analysis of TCGA gene expression data, CDK1 expression in lung adenocarcinoma was higher than that in normal lung tissues. UALCAN analysis showed that high CDK1 expression may be associated with smoking. Survival analysis indicated that when CDK1 gene was highly expressed, patients with lung adenocarcinoma had a poor prognosis. Univariate and multivariate Cox regression analysis of CDK1 expression and overall survival showed that high CDK1 expression was an independent risk factor for survival of patients with lung adenocarcinoma. Gene set enrichment analysis revealed that high CDK1 expression was closely related to DNA replication, cell cycle, cancer pathway and p53 signaling pathway. Conclusion    CDK1 may be a potential molecular marker for prognosis of lung adenocarcinoma. In addition, CDK1 regulation may play an important role in DNA replication, cell cycle, cancer pathway and p53 signaling pathway in lung adenocarcinoma.

Objective To discuss the characteristics of clinical presentation,neuroimaging and genetics in a Chinese family of oculeptomeningeal amyloidosis (OLMA) associated with the transthyretin (TTR) Leul2Pro mutation.Methods Clinical characteristics of the pedigree and peripheral blood samples of an OLMA patient with TTR Leu12Pro mutation were collected from Tangdu Hospital on September 25,2015.Firstly,exon detection was performed on the proband and the family validation of her father and sister was carried out.The clinical,neuroimaging and genetic characteristics of the disease were analyzed.Results A 36-year-old right-handed woman was suffered recurrent episodes of slurred speech with right-sided weakness.She presented initi.ally with headache,autonomic dysfunction,visual and hearing loss.Magnetic resonance imaging showed extensive leptomeningeal enhancement,and cerebrospinal fluid analysis showed a raised protein of 1566.54 mg/L.The examination of the both eyes showed dry eye,vitreous opacity,and mild cataract.The proband and her sister,the sister's eldest daughter,the proband's son showed c.95T＞C mutation in exon2 of TTR gene and Leu12Pro mutation in TTR protein.Conclusions OLMA should be suspected if central nervous system symptoms are observed in combination with one or more of the following:family history of a neuropathy,autonomic dysfunction,cardiac hypertrophy,hear or ocular involvement,gadolinium-enhanced magnetic resonance imaging of the brain and spine revealing diffuse leptomeningeal enhancement,lumbar puncture demonstrating elevated protein without evidence of malignant cells on cytology.Genetic testing for pathogenic mutation in TTR gene is helpful for diagnosis of OLMA.