Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

OBJECTIVES: To analyze bone mass distribution and the factors affecting bone mass in a general Chinese Han cohort undergoing physical examinations at our center. METHODS: We retrospectively collected the data of bone mineral density (BMD) measurements from 30 599 healthy Han Chinese adults (age≥20 years) who underwent dual-energy X-ray absorptiometry scans at our hospital from July, 2013 to July, 2023. Basic parameters including height, body weight, and gender were recorded, and descriptive statistics and correlation analyses were performed using R software. RESULTS: In this cohort, the male individuals had a mean peak BMD of 1.00±0.12 g/cm² in the lumbar vertebrae, 0.94±0.14 g/cm² in the femoral neck, and 0.99±0.13 g/cm² in the total hip, significantly higher than the values in the female individuals [0.99±0.12 g/cm² in the lumbar vertebrae (P=0.022), 0.79±0.11 g/cm² in the femoral neck (P<0.001), and 0.88±0.11 g/cm² in the total hip (P<0.001)]. In the overall cohort, the BMD values of the lumbar spine and femur decreased with age after reaching their peak levels. There was a positive correlation between BMD value and body mass index (BMI) in both male and female individuals. The 2013-2014 period recorded the lowest BMD values in the lumbar, hip, and femoral neck, which tended to increase steadily in the following years (2015-2023). CONCLUSIONS Our data suggest that the BMD values vary among different populations, and future multi-center studies using more accurate BMD detection technology are warranted to capture the variation patterns of BMD with demographic characteristics of specific populations.
Humans ; Bone Density ; Absorptiometry, Photon ; Male ; Female ; Retrospective Studies ; Osteoporosis/diagnostic imaging* ; Adult ; Middle Aged ; Lumbar Vertebrae/diagnostic imaging* ; China/epidemiology* ; Femur Neck/diagnostic imaging* ; Aged ; Beijing/epidemiology* ; Young Adult

Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca²⁺ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca²⁺ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m⁶A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca²⁺ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.
Animals ; Diabetic Cardiomyopathies/pathology* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac/metabolism* ; Mice ; Calsequestrin/genetics* ; Calcium/metabolism* ; Male ; Sarcoplasmic Reticulum/metabolism* ; Methyltransferases/metabolism* ; Mice, Inbred C57BL ; Mitochondria, Heart/metabolism* ; Disease Models, Animal ; Mitochondria/metabolism*

Inflammation is associated with the occurrence and recurrence of ischemic stroke, and patients with coronary artery disease who receive colchicine treatment have a lower incidence of vascular events. However, the efficacy and safety of anti-inflammatory therapy with colchicine in preventing recurrent stroke is unclear. This article reviews the relevant mechanisms of action of colchicine and its role in the prevention of ischemic stroke, aiming to provide reference for the secondary prevention of ischemic stroke.

AIM:To explore the therapeutic effect of teprenone(geranylgeranylacetone,GGA)on lipopolysac-charide(LPS)-induced cardiac dysfunction and its mechanism.METHODS:(1)Eight-week-old male C57BL/6 wild-type mice and carboxyl terminus of heat shock protein 70(HSP70)-interacting protein(CHIP)gene knockout mice were randomly divided into control group,LPS group,LPS+GGA group and GGA group,with 8 mice in each group.The model was established by intraperitoneal injection of LPS(25 mg/kg),and 1 h after LPS stimulation,mice were given intraperito-neal injection of GGA(100 mg/kg).The technique of high-resolution ultrasonography system was used to evaluate the car-diac function of mice.The serum of mice from each group were collected to detect the levels of creatine kinase-MB(CK-MB)and lactate dehydrogenase(LDH).HE staining was performed to observe histological changes of cardiac tissues.ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in cardiac tissues.West-ern blot was used to detect the protein levels of HSP70,CHIP,karyopherin-α 2(KPNA2),myeloperoxidase(MPO),vas-cular cell adhesion molecule(VCAM),intercellular cell adhesion molecule(ICAM),and nuclear factor-κB(NF-κB)in cardiac tissues.(2)In vitro cell inflammation model was established using mouse myocardial cells HL-1 stimulated with LPS.ELISA was used to detect the levels of TNF-α and IL-6 in cell supernatants.Western blot was used to detect the pro-tein expression levels of HSP70,CHIP,and KPNA2 in myocardial cells.Immunofluorescence staining was performed to observe the content of nuclear NF-κB.RESULTS:(1)GGA effectively improved cardiac function of LPS-stimulated mice,significantly increased ejection fraction and left ventricular fractional shortening(P<0.01),reduced serum levels of CK-MB and LDH(P<0.01),and alleviated myocardial injury.(2)GGA significantly reduced the release of TNF-α and IL-6 caused by LPS(P<0.01),as well as nuclear translocation of NF-κB,decreased the levels of KPNA2,MPO,VCAM and ICAM in cardiac tissues,and increased the levels of HSP70 in cardiac tissues and cells(P<0.01).(3)In CHIP knockout myocardial cells and mice,GGA failed to inhibit LPS-induced inflammatory response and lost its effect on im-proving cardiac function.CONCLUSION:The protective effect of GGA against LPS-caused cardiac dysfunction of mice is related to increasing expression of HSP70 and promoting CHIP activation,which inhibits the translocation of NF-κB into nucleus and suppresses inflammatory factor release.CHIP knockout abolishes the effects of GGA on reducing LPS-induced inflammatory response and myocardial injury.

Objective:To explore the value of difference value and relative value of pulmonary vascular quantitative parameters of biphasic CT in diagnosis of chronic obstructive pulmonary disease (COPD) and high-risk groups.Methods:The study was a cross-sectional study. A retrospective study of 624 patients who underwent biphasic chest CT scanning in the Second Affiliated Hospital of PLA Naval Medical University from August 2018 to December 2020. Subjects were divided into three groups according to pulmonary function test: normal group ( n=321), preserved ratio impaired spirometry (PRISm) ( n=204) and COPD group ( n=99). The pulmonary vascular quantitative parameters were obtained by the workstation, including the number of pulmonary vessels (N total), cross-sectional area less than that of 5 mm 2 (N CSA5), vessel area (VA total) of 9, 12, 15, 18, 21 mm from the pleura, total blood vessels volume (TBV) and total blood vessels volume under 5 mm 2 (BV5) at expiratory and inspiratory phase. The difference value, relative value of biphasic CT were calculated. ANOVA test or Kruskal-Wallis H test was used to compare the differences of pulmonary vascular quantitative parameters among the three groups, and LSD or Bonferroni tests were used for multiple comparisons. Results:The N total, N CSA5, VA total of the whole lung in the inspiratory phase at the level of 9, 12, 15, 18 and 21 mm from the pleura and TBV, BV5 in the normal group, PRISm group and COPD group, showed an overall trend of decreasing and then increasing, and the PRISm group was lower than those of the normal group ( P<0.05). The differences in N total, N CSA5, VA total between the COPD group and the normal group at the level of 9 and 21 mm from the pleura were not statistically significant ( P>0.05), while the N total, N CSA5, V Atotal of biphasic difference value and relative value in COPD group demonstrated a significant difference from those in normal group ( P<0.05). Conclusion:The difference value and relative value of pulmonary vascular quantitative parameters in biphasic CT are more useful than single inspiratory-phase vascular parameters to differentiate the changes in pulmonary vascular remodeling between COPD patients and the normal population, and also to complement the pulmonary vascular characteristics of the PRISm population, which can provide a basis for early warning of COPD and high-risk populations.

To report a case of clonorchiasis (Clonorchis sinensis infection) combined with intrahepatic cholangiocarcinoma and review relevant literature to improve the awareness of the clinical physicians regarding Clonorchis Sinensis and provide references for clinical diagnosis and treatment. A retrospective analysis was conducted on a case of clonorchiasis combined with intrahepatic cholangiocarcinoma, admitted to Guangzhou Red Cross Hospital of Jinan University on March 15, 2021, along with a review of related literature. The patient, a 55-year-old male, presented with abdominal distension and poor appetite for over two months and had a history of diabetes and hypertension for many years. He had been consuming raw fish for more than ten years. Upon admission, physical examination revealed a solid mass measuring 8 cm×8 cm was palpable below the xiphoid process in the upper abdomen, with an uneven surface, slightly hard texture, poor mobility, and positive tenderness. Laboratory tests revealed the presence of Clonorchis Sinensis eggs in the stool, and the patient tested positive for Clonorchis Sinensis IgG antibodies. After a comprehensive evaluation that included abdominal ultrasound, abdominal plain CT scan, and contrast-enhanced CT, the patient was diagnosed with "intrahepatic cholangiocarcinoma with multiple intrahepatic metastases." Due to the patient's poor liver function, praziquantel was not administered, and albendazole was instead used at a dose of 10 mg/(kg·d) once daily for seven days. Upon re-admission one month after discharge, no Clonorchis Sinensis eggs were found in the stool. A follow-up after 12 months revealed that the patient had passed away due to liver failure. The serious infection of Clonorchis Sinensis is relatively rare, but it can lead to severe consequences in high-risk individuals, especially when it progresses to intrahepatic cholangiocarcinoma. Clinicians should enhance their awareness of clonorchiasis and promptly identify and provide symptomatic treatment for infections, as early as possible and provide appropriate treatment. Early diagnosis and treatment are crucial for improving the prognosis of patients.

Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.

Objective:To explore the differences of functional small airway and pulmonary vascular parameters in chronic obstructive pulmonary disease (COPD) of different imaging phenotypes.Methods:One hundred and thirty COPD patients underwent biphasic CT scanning in Shanghai Changzheng Hospital from August 2018 to August 2020 were analyzed retrospectively. The patients were classified into three phenotypes based on the presence of emphysema and bronchial wall thickening on CT images. Phenotype A: no emphysema or mild emphysema, with or without bronchial wall thickening; Phenotype E: obvious emphysema without bronchial wall thickening; phenotype M: significant emphysema and bronchial wall thickening were present. Parametric response map (PRM) and pulmonary vascular parameters were quantitatively measured at the whole lung level. PRM parameters included the volume of emphysema (PRMV Emphysema), the volume of functional small airway (PRMV fSAD), the volume of normal pulmonary parenchyma (PRMV Normal) and its volume percentage (%). Pulmonary vascular parameters included the number of vessels (N) and cross-sectional area vessels<5 mm 2 (N -CSA<5) at 6, 9, 12, 15, 18 21, 24 mm distance from the pleura. ANOVA or Kruskal-Wallis H tests were used to compare the differences for PRM and pulmonary vascular parameters among the three phenotypes, and LSD or Bonferroni tests were used for multiple comparisons. Results:There were significant differences among the three phenotypes for PRMV fSAD, PRMV Emphysema, PRMV fSAD%, PRMV Emphysema%, and PRMV Normal% at the whole lung level ( P<0.05). PRMV Emphysema, PRMV Emphysema%, PRMV Fsad, PRMV fSAD% of phenotype A were lower than those of phenotype E and M ( P<0.001), while there was no significant difference for PRMV Emphysema, PRMV Emphysema%, PRMV fSAD, PRMV fSAD% between phenotype E and phenotype M ( P>0.05). There were significant differences in N and N -CSA<5 that 6 mm distance from the pleura among the three groups( P<0.05). Among them, N and N -CSA<5 that 6 mm distance from pleura in phenotype M were significantly lower than those in phenotype A( P<0.001,0.002); No significant differences was found in N between phenotype M and phenotype E( P>0.05), while there was significant differences in N -CSA<5 between phenotype M and phenotype E( P=0.034). Conclusion:Biphasic quantitative CT analysis can reflect the heterogeneity of the functional small airways and pulmonary vascular abnormality in COPD with different phenotypes, and provide objective evidence for individualized diagnosis and treatment.

Objective:To analyze the value of shear wave elastography (SWE) in evaluating carotid artery elasticity in type 2 diabetes mellitus (T2DM) patients with nonalcoholic fatty liver disease (NAFLD).Methods:A total of 98 T2DM patients diagnosed in the Second Affiliated Hospital of Dalian Medical University were selected and divided into three groups according to the results of liver ultrasound examination. 35 patients without NAFLD were in group A, 33 patients with mild NAFLD were in group B, and 30 patients with moderate to severe NAFLD were in group C. All selected individuals showed no plaque formation on carotid ultrasound examination. Left carotid artery intima-media thickness (IMT), carotid artery systolic diameter (Ds), carotid artery diastolic diameter (Dd), and peak systolic velocity (PSV) were measured using conventional two-dimensional and M-mode ultrasound. The stiffness coefficient (β) was obtained through calculation. SWE was used to measure the mean longitudinal modulus of elasticity (MEmean), mean minimum modulus of elasticity (MEmin), and mean maximum modulus of elasticity (MEmax) of the left carotid artery at the end of diastole.Results:There was no statistically significant difference in Ds, Dd, and PSV among the three groups (all P>0.05). Compared with group A and group B, group C had significantly higher IMT, β, MEmean, MEmax, and MEmin (all P<0.05). Compared with the group A, the group B had higher levels of MEmean, MEmax, and MEmin (all P<0.05), there was no statistically significant difference in IMT and β between the groups (all P>0.05). Correlation analysis showed that MEmax, MEmean, and MEmin in each group were positively correlated with β ( r=0.537, 0.543, 0.525, P<0.01), and also positively correlated with HbA 1c ( r=0.456, 0.483, 0.438, P<0.01), but not with IMT (all P>0.05). The intra observer Intraclass correlation coefficient (ICC) of MEmax, MEmean and MEmin measured by SWE was 0.847-0.887, and the inter observer ICC was 0.791-0.934, indicating a good repeatability. Conclusions:SWE can quantitatively evaluate the elasticity of the carotid artery in patients with T2DM and NAFLD.