Objective: To prospectively evaluate the feasibility, accuracy, and safety of multiparameter MRI-guided percutaneous biopsy using a 1T open MRI scanner for evaluating suspicious centrally located lung lesions with associated post-obstructive atelectasis. Materials and Methods: In this single-center study, MRI-guided percutaneous coaxial cutting biopsy was performed for 107 suspicious central lung lesions with associated post-obstructive atelectasis in 107 patients between July 2015 and December 2020. A fast T2-weighted imaging (T2WI)-turbo spin echo (TSE) sequence and an enhanced fast T1-weighted imaging (T1WI)-TSE sequence were used to identify, localize, and biopsy lung lesions, and diffusion-weighted imaging (DWI) was used as a supplementary sequence for identifying the lesion location. The final diagnosis was confirmed by surgical histopathology or clinical follow-up for a minimum of 24 months. The sensitivity, specificity, and accuracy for diagnosing lung malignancies were calculated, and the complications were recorded for each case. Results: Using multiparameter MRI, central lung lesions could be clearly distinguished from post-obstructive atelectasis in 96 patients (89.7%). The sensitivity, specificity, and accuracy of MRI-guided percutaneous biopsy for diagnosing lung malignancy was 97.0% (98/101), 100% (6/6), and 97.2% (104/107), respectively. Self-limited hemoptysis occurred in three patients. Pneumothorax occurred in five patients, of which none required pleural drainage. No serious procedure-related complications were observed. Conclusion As a technology that does not involve ionizing radiation, multiparameter MRI-guided percutaneous coaxial cutting biopsy is a safe and accurate diagnostic technique for evaluating centrally located lung lesions associated with post-obstructive atelectasis.

Objective:To investigate the potential characteristic manifestations and application value of the Dynamic Visual Acuity Test（DVAT） in vestibular migraine（VM）. Methods:A total of 50 VM patients（case group） and 50 healthy subjects（control group） diagnosed at the Department of Otorhinolaryngology Head and Neck Surgery, First Hospital of Shanxi Medical University between November 1, 2023, and December 31, 2024, were enrolled. The case group underwent DVAT, video head impulse test（vHIT）, caloric test, and Dizziness Handicap Inventory（DHI） assessment, whereas the control group only received DVAT. Group-based analyses were conducted to examine the effect of age on Dynamic Visual Acuity Loss（DVALoss）, as well as the correlations of DVALoss with vestibular function tests and DHI scores. Results:DVALoss in the case group was significantly higher than that in the control group（P<0.001）. In both groups, age was significantly and positively correlated with DVALoss（P<0.001）. Within the case group, DVALoss was strongly and positively correlated with DHI scores（r=0.807, P<0.001）; it was negatively correlated with the vestibulo-ocular reflex（VOR） gain in vHIT, though without clinical significance, and showed no significant association with the caloric test. Age and DVALoss collectively accounted for 71.3% of the variance in DHI scores（R²=0.713）, with age exerting a relatively minor actual impact. Conclusion:DVAT can sensitively identify the core functional impairments of VM. DVALoss, as a direct functional reflection of the pathological mechanism of VM, is strongly correlated with DHI scores. Incorporating DVALoss into standardized assessments may provide an objective basis for the diagnosis and management of VM.
Humans ; Migraine Disorders/diagnosis* ; Visual Acuity ; Case-Control Studies ; Head Impulse Test ; Vestibular Function Tests ; Female ; Male ; Adult ; Vestibular Diseases/physiopathology* ; Middle Aged ; Caloric Tests

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

Objective: To prospectively evaluate the feasibility, accuracy, and safety of multiparameter MRI-guided percutaneous biopsy using a 1T open MRI scanner for evaluating suspicious centrally located lung lesions with associated post-obstructive atelectasis. Materials and Methods: In this single-center study, MRI-guided percutaneous coaxial cutting biopsy was performed for 107 suspicious central lung lesions with associated post-obstructive atelectasis in 107 patients between July 2015 and December 2020. A fast T2-weighted imaging (T2WI)-turbo spin echo (TSE) sequence and an enhanced fast T1-weighted imaging (T1WI)-TSE sequence were used to identify, localize, and biopsy lung lesions, and diffusion-weighted imaging (DWI) was used as a supplementary sequence for identifying the lesion location. The final diagnosis was confirmed by surgical histopathology or clinical follow-up for a minimum of 24 months. The sensitivity, specificity, and accuracy for diagnosing lung malignancies were calculated, and the complications were recorded for each case. Results: Using multiparameter MRI, central lung lesions could be clearly distinguished from post-obstructive atelectasis in 96 patients (89.7%). The sensitivity, specificity, and accuracy of MRI-guided percutaneous biopsy for diagnosing lung malignancy was 97.0% (98/101), 100% (6/6), and 97.2% (104/107), respectively. Self-limited hemoptysis occurred in three patients. Pneumothorax occurred in five patients, of which none required pleural drainage. No serious procedure-related complications were observed. Conclusion As a technology that does not involve ionizing radiation, multiparameter MRI-guided percutaneous coaxial cutting biopsy is a safe and accurate diagnostic technique for evaluating centrally located lung lesions associated with post-obstructive atelectasis.

OBJECTIVE To evaluate the effects of phthalic acid esters(PAEs)on the expression of heme oxygenase-1(HO-1)in HepG2 cells,and to construct an HO-1-based three-dimensional quantita-tive structure-activity relationship(3D-QSAR)model.METHODS ① HepG2 cells were treated with seven types of PAEs:di-(2-ethylhexyl)phthalate(DEHP),di-n-octyl phthalate(DnOP),dimethyl phthalate(DMP),diethyl phthalate(DEP),dihexyl phthalate(DHXP),dimethylglycol phthalate(DMEP),and dibutyl phthalate(DBP),at final concentrations of 0(DMSO,solvent control),0.062 5,0.125,0.25,0.5 and 1 mmol·L-1(n=6)for 48 h at 37℃.The expression level of HO-1 was measured by Western blotting.② A 3D-QSAR model was constructed using comparative molecular similarity indices analysis(CoMSIA)based on the measured HO-1 levels.The applicability domain(AD)of the model was evaluated using the leverage method.Model fitting quality and predictive ability were evaluated via the KNIME Enalos+node to verify model stability.Additionally,molecular docking was performed to validate the binding interactions between PAEs and HO-1.RESULTS ① Compared with the solvent control group,48 h of exposure to 0.062 5 mmol·L-1 PAEs(DMP,DMEP,DEHP,DnOP and DEP)significantly increased HO-1 protein expressions,while 1 mmol·L-1 PAEs(DMP,DBP,DnOP,DEP and DHXP)significantly suppressed HO-1 expressions.② The 3D-QSAR model showed a non-cross-validated coefficient(R2)of 0.996 and a cross-validated coefficient(Q2)of 0.548.All the seven PAEs in the 3D-QSAR model were within the applicability domain(AD)and passed external validation.Molecular docking results indi-cated that DBP,DnOP,DEHP and DHXP exhibited stronger binding affinities to HO-1.CONCLUSION Forty-eight hours of exposure of HepG2 cells to 1 mmol·L-1 PAEs can significantly suppress HO-1 expres-sions.The 3D-QSAR model established in this study provides a potential tool for predicting the HO-1-related toxic effects of novel PAEs.

Objective To detect the expression of lactate dehydrogenase A(LDHA),FoxP3,and CD4 in hepatocellular carcinoma(HCC)and to analyze the effect of bufalin on LDHA as well as on the differentiation and function of regulatory T(Treg)cells in the tumor microenvironment of HCC mice.Methods Immunohistochemical staining was performed to detect the difference in the expression of LDHA,FoxP3(Treg cell marker),and CD4 between the tumor and adjacent tissues from 91 HCC patients.Hepl-6 subcutaneous tumor-bearing mouse model was established.The mice were randomly divided into control,bufalin+pyruvic acid,oxalate,and bufalin groups(n=5 each group).The mass and volume of subcutaneous tumors were compared.Immunohistochemical staining was performed to detect the expression of LDHA,FoxP3,and CD4 in tumors of mice in each group.ELISA was used to detect the levels of transforming growth factor β(TGF-β)and interleukin-10(IL-10)in the serum of mice in each group to evaluate the immune function of Treg cells.Results Compared with adjacent tissues,HCC tissues exhibited significantly higher LDHA and FoxP3 expression and lower CD4 expression(P＜0.001).The results of the correlation analysis showed that LDHA was positively correlated with FoxP3 expression and negatively correlated with CD4 expression(P＜0.05).The experimental results of Hep1-6 subcutaneous tumor-bearing mice showed that the tumor volume was significantly smaller in the bufalin and oxalate groups than in the control group and was significantly larger in the bufalin+pyruvic acid group than in the bufalin group(P＜0.001).The results of immunohistochemical staining showed that the expression levels of LDHA and the percentage of FoxP3+cells in the bufalin and oxalate groups were significantly lower than those in the control group,and the percentage of CD4+cells in the bufalin group was significantly higher than that in the control group(P＜0.001).The expres-sion level of LDHA and the percentage of FoxP3+cells in the bufalin+pyruvic acid group were significantly higher than those in the bufalin group,while the percentage of CD4+cells was significantly lower than that in the bufalin group(P＜0.001).The results of ELISA showed that the levels of TGF-β and IL-10 in the bufalin and oxalate groups were significantly lower than those in the control group(P＜0.001).Conclusion Bufalin inhibits cell growth,downregulates LDHA expression,and suppresses the differentiation and proliferation of Treg cells in HCC mice.

Objective This study sought to establish a diarrhea-predominant irritable bowel syndrome(IBS-D)mouse model by gavage different mass concentrations sennae folium combined with chronic restraint stress,and to determine the appropriate mass concentration of sennae folium to establish IBS-D mouse model.Methods The mass concentration of sennae folium used for the IBS-D mouse model followed suggested amounts in the literature and on that basis,the mass concentration gradient was established prior to conducting the experiment.Female C57BL/6 mice were divided into a normal group(Group N),a low-dose group(Group L;0.25 g/mL sennae solution),a medium-dose group(Group M;0.50 g/mL sennae solution),and a high-dose group(Group H;1.0 g/mL sennae solution),with 10 mice per group.After 14 days,the defecation,diarrhea index,visceral sensitivity,and morphological changes in the colonic tissue in each group were observed and recorded to compare the differences among models established with varying mass concentrations of sennae folium.Results Compared with Group N(42.90±11.90)%,Group L(80.30±5.77)%,Group M(80.50±3.44)%,and Group H(81.90±2.68)%had significantly higher 6 h fecal water content(P＜0.01).Compared with Group N(0.00±0.00),the diarrhea index of mice in Group L(0.57±0.16),Group M(0.62±0.23),and Group H(0.60,0.23)also increased significantly(P＜0.01).Compared with Group N(0.65(0.60,0.65)),Group M(0.32(0.24,0.39))and Group H(0.34(0.27,0.47))had significantly lower visceral pain threshold and higher visceral sensitivity(P＜0.01).Additionally,the first blue stool time in Group M(98.15(93.41,100.44)min)was significantly shorter than that in Group N(186.81(109.28,192.05)min)(P＜0.01),and the total number of stools in Group M(22.4±3.73)was significantly higher than that in Group N(17.90±4.48)(P＜0.05).Conclusions Compared with 0.25 and 1.0 g/mL,0.50 g/mL sennae folium gavage,combined with chronic restraint stress,can better simulate the clinical symptoms of IBS-D.

Irritable bowel syndrome(IBS)is a prevalent functional gastrointestinal disorder characterized by a complex etiology involving multiple interacting factors.Accumulating evidence in recent years has indicated that intestinal barrier dysfunction may play a crucial role in the pathogenesis of IBS.This review systematically ex-amines the impact of intestinal barrier dysfunction on IBS,analyzing its associations with the mechanical,im-mune,chemical,and microbial components of the gut barrier,as well as current clinical treatment approaches.Moreover,this paper highlights the potential of intestinal barrier repair mechanisms as therapeutic targets,which may provide novel insights and directions for understanding the underlying pathophysiological mechanisms and de-veloping effective interventions for IBS.