OBJECTIVES: To investigate the role and mechanism of Brahma-related gene 1 (Brg1) in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia (BPD) model. METHODS: Wild-type C57BL/6 and Brg1^f1/f1 mice were randomly divided into four groups: wild-type control, wild-type BPD, Brg1^f1/f1 control, and Brg1^f1/f1 BPD (n=5 each). Immortalized mouse pulmonary alveolar type 2 cells (imPAC2) were cultured, and Brg1 gene was knocked down using lentivirus transfection technology. Cells were divided into three groups: control, empty vector, and Brg1 knockdown. Hematoxylin and eosin staining and immunofluorescence were used to detect pathological changes in mouse lung tissue. Western blot and real-time fluorescent quantitative PCR were used to measure Brg1 protein and mRNA expression levels in mouse lung tissue. Western blot and immunofluorescence were used to detect the expression of homeodomain-containing protein homeobox (HOPX), surfactant protein C (SPC), and Wnt/β-catenin signaling pathway proteins in mouse lung tissue and imPAC2 cells. The CCK8 assay was used to assess the proliferation of imPAC2 cells, and co-immunoprecipitation was performed to verify the interaction between Brg1 and β-catenin proteins in imPAC2 cells. RESULTS: Compared to the Brg1^f1/f1 control group and wild-type BPD group, the Brg1^f1/f1 BPD group showed increased alveolar diameter and SPC protein expression, and decreased relative density of pulmonary vasculature and HOPX protein expression (P<0.05). Compared to the control group, the Brg1 knockdown group showed increased cell proliferation ability, protein expression levels of SPC, Wnt5a and β-catenin, and β-catenin protein fluorescence intensity, along with decreased HOPX protein expression (P<0.05). An interaction between Brg1 and β-catenin proteins was confirmed. CONCLUSIONS The Brg1 gene may promote the proliferation of alveolar type 2 epithelial cells by regulating the Wnt/β-catenin signaling pathway, thus influencing the occurrence and development of BPD.
Animals ; DNA Helicases/genetics* ; Transcription Factors/genetics* ; Wnt Signaling Pathway/physiology* ; Nuclear Proteins/genetics* ; Mice ; Bronchopulmonary Dysplasia/etiology* ; Mice, Inbred C57BL ; beta Catenin/physiology* ; Disease Models, Animal ; Cell Proliferation ; Lung/pathology* ; Male

Objective To investigate the alterations of cerebral blood flow(CBF)in type 2 diabetic mellitus(T2DM) patients without cognitive impairment by using arterial spin labeling(ASL)technique.Methods A total of 23 T2DM patients without cognitive impairment and 23 healthy controls(HC)matched by age,sex,and education attainment were recruited.Their clinical data were collected,and neuropsychological tests and cerebral magnetic resonance imaging were performed.Then,the outcomes of clinical features,neuropsychological tests,and global and regional CBF were compared between the two groups.The significant regional zCBF(z-transformed relative CBF)values were extracted and correlated with clinical data and neuropsychological scores in T2DM patients,controlling age,sex,and education.Results No significant difference was found in whole brain CBF between the two groups(P=0.155),while significantly higher CBF was identified in the left superior temporal gyrus and left insula in the T2DM group(Gaussian random field correction,initial threshold P < 0.001,cluster level P < 0.05).No correlation was observed between the significant regional zCBF values and the clinical data or the neuropsychological scores in T2DM patients(all P>0.05).Conclusion Alterations in cerebral hemodynamics may precede cognitive function changes in T2DM,suggesting that the ASL technique is promising for early monitoring of cerebral hemodynamic changes associated with cognitive impairment in patients with T2DM.
Humans ; Diabetes Mellitus, Type 2/physiopathology* ; Cerebrovascular Circulation ; Middle Aged ; Male ; Female ; Magnetic Resonance Imaging ; Case-Control Studies ; Cognitive Dysfunction ; Neuropsychological Tests ; Aged

Immune checkpoint inhibitor-associated enterocolitis is an immune-related adverse reaction during tumor treatment with immune checkpoint inhibitors.In this article,we present the clinical data and ultrasound manifestations of a patient with immune checkpoint inhibitor-associated enterocolitis,aiming to share diagnostic and therapeutic insights.
Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Enterocolitis/chemically induced* ; Ultrasonography ; Male

Chiral drugs are closely related to the safety and effectiveness of drug use.Most dihydropyridine drugs have chiral carbon atoms,which are used as racemes and produce stereoselective disposal characteristics after entering the body,and may affect the safety and effectiveness of drugs.Therefore,based on the chiral resolution and pharmacokinetic characteristics of this class of drugs,the selection rules of chiral HPLC and CE methods and in vivo analysis applications of this class of drugs in recent years were reviewed.The stereoselective pharmacokinetics of this class of drugs were listed and compared.It was found that some of these drugs had obvious differences in stereoselective pharmacokinetics,and the pharmacokinetics and toxicity in vivo were also different.

BACKGROUND:The stability of the pelvis is mainly determined by the posterior pelvic ring and the sacroiliac joint.The posterior pelvic ring injury and the dislocation of the sacroiliac joint caused by high energy impacts such as car accidents increase year by year.Surgical treatment is the best method,and there are many kinds of endophytorepair methods in clinical practice,but which treatment method has the best biomechanical properties is still controversial. OBJECTIVE:To compare the biomechanical properties of three kinds of internal implants:anterior double plates,posterior bridging plate and tension nail in the repair of unilateral unstable pelvic posterior ring injury,to provide a reference for the clinical treatment and development of a new pelvic tension screw. METHODS:(1)Finite element simulation:Mimics,Wrap and SolidWorks were used to establish normal pelvic model,unilateral injured pelvis model,and three kinds of internal implant repaired models(anterior double plates,posterior bridging plate and tension nail).Ansys was used to analyze the stress and deformation of the models.(2)Biomechanical test:A total of 15 intact pelvic specimens were randomly grouped into five groups,normal pelvic model,unilateral injured pelvis model,anterior double plates,posterior bridging plate and tension nail groups.The mechanical test was performed using an Instron E10000 testing machine. RESULTS AND CONCLUSION:(1)Simulation:In the normal pelvic model,the average displacement of the sacrum was 0.174 mm,and the maximum stress of the sacral iliac bone was 10.51 MPa,and the stress distribution was uniform.The mean sacral displacement of the unilateral injured pelvis model was 0.267 mm,and the stress concentration of the model was obvious.The mean displacement of the sacrum in the three repaired models was close to that in the normal pelvic model,and the stress distribution of the sacral iliac bone in the tension nail repaired model was uniform.(2)Mechanical test:The stiffness of the normal pelvic model was(226.38±4.18)N/mm,and that of the unilateral unstable pelvic model was the smallest(130.02±2.19)N/mm.The deviation of the normal pelvic model stiffness and the three repaired models'stiffness were all within(±10%),and the repair effect was obvious.(3)The simulation results were in agreement with the experimental results.(4)The biomechanics of the tension nail repaired model was the most similar to that of the normal pelvis,and this method was the best.The repairing stiffness of the anterior double plate was too large,and the stress shielding effect was more significant.The posterior bridging plate repair could not solve the compensatory effect of the normal side soft tissue and had defects.This study provides an optimal basis for clinical surgery.(5)The new type of pelvic tension nail should be improved from the point of view of the tension nail to retain the good biomechanical properties of the tension nail,while adding other advantages,such as being used for the osteoporotic pelvis.

Objective To investigate the inhibitory effect of toosendanin on the growth of lung adenocarcinoma cells in vitro and in vivo by regulating the expression of cell division cycle associated protein 5(CDCA5).Methods The expression of CDCA5 in different lung tissues was analyzed in TCGA database.The expression level of CDCA5 in BEAS-2B cells and A549 cells was detected by Western blot.The effect of different concentrations of toosendanin on the viability of A549 cells was determined by cell counting kit-8(CCK-8)assay.The A549 cells were randomly divided into 4 groups:control group(normal cells cultured normally),toosendanin group(normal cells cultured with 40 μmol·L-1 toosendanin),toosendanin+pcDNA group(cells transfected with pcDNA empty vector and cultured with 40 μmol·L-1 toosendanin),and toosendanin+CDCA5 group(cells transfected with CDCA5 overexpression vector and cultured with 40 μmol·L-1 toosendanin).After 48 h of cultivation,the proliferation and apoptosis of each group of cells were detected by CCK-8 and flow cytometry,and the expression of proliferation and apoptosis related proteins in each group of cells was detected by Western blot.The BALB/c nude mice were randomly divided into sh-NC and sh-CDCA5 stable transfected cell lines with nude mouse xenograft models.Daily intraperitoneal injection of 0.9％NaCl and 40μmol·L-1 toosendanin solution was given to observe and record the changes in tumor tissue volume and body mass.Results The results of CCK-8 showed that after 48 hours,the survival rates of A549 cells treated with 10,20,30,40,50,60 and 70 μmol·L-1 toosendanin were(80.74±8.71)％,(72.96±6.53)％,(61.01±4.86)％,(51.20±3.13)％,(42.10±5.94)％,(38.93±3.18)％and(33.48±2.94)％,respectively.Toosendanin significantly inhibited the proliferation of A549 cells.The proliferation rates of cells in the control group,toosendanin group,toosendanin+pcDNA group,and toosendanin+CDCA5 group were(100.00±4.19)％,(49.18±6.70)％,(55.75±5.74)％,and(77.66±7.48)％,respectively;the expression levels of CDCA5 protein were 1.08±0.11,0.44±0.04,0.43±0.05 and 0.99±0.10,respectively.The expression levels of CDCA5 protein in tumor tissues of nude mice in the sh-NC group,sh-CDCA5 group,toosendanin+sh-NC group,and toosendanin+sh-CDCA5 group were 1.04±0.14,0.42±0.04,0.56±0.08 and 0.32±0.04,respectively.Compared with the sh-NC group,the tumor blocks formed by nude mice in other groups were significantly smaller,and the tumor volume and weight were significantly lower(all P＜0.05).Compared with the toosendanin+sh-NC group,the toosendanin+sh-CDCA5 group had more significant inhibitory effect on tumor formation,and the difference was statistically significant(P＜0.05).Conclusion Toosendanin can inhibit the growth of lung adenocarcinoma cells in vitro and in vivo,which is mainly related to the inhibition of CDCA5 expression.

The number of type 2 diabetes(T2DM)accounts for more than 90％of all Diabetes mellitus(DM).The decrease of islet β cell mass and dysfunction are the core links of T2DM.With the prolongation of the course of disease,the number and function of β cells are gradually attenuated,and the damage mechanism has not been elucidated.At present,it is believed that it is closely related to metabolic stress,abnormal regulation of insulin secretion,changes in islet microenvironment,mitochondrial damage,glycolipid toxicity and dedifferentiation of islet β cells.Therefore,the mechanism of islet β cell damage in T2DM is summarized and elaborated in order to provide some reference for the precise intervention of T2DM.

Objective To investigate the occurrence of adverse events of lurasidone in the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database by using Open Vigil FDA2.1,to enrich the experience and provide the basis for the clinical use of the drug in China.Methods Using Open Vigil FDA2.1,adverse event data were extracted from the FAERS database for a total of 51 quarters from the 4th quarter of 2010 to the 3rd quarter of 2023,and the ratio of reporting ratio(ROR)method and the proportional reporting ratio(PRR)method were used for data mining and analysis.Results A total of 32 728 adverse event reports with lurasidone as the first suspected drug was obtained,with a larger proportion of females(54.26％)and occurring mostly in adults(18 to 59 years).After the screening,326 preferred term(PT)signals were obtained,involving 20 system-organ classifications(injury,poisoning and procedural complications,general disorders and administration site conditions,psychiatric disorders,etc.).Among them,PTs with the higher frequency of occurrence included off label use,feeling abnormal,crying,anxiety,depression,insomnia,etc.PTs with stronger signal strength included activation syndrome,mania,tongue movement disturbance,hypoprolactinaemia,akathisia,etc.Multiple new suspected adverse drug reactions were unearthed,including hypoprolactinaemia,emotional poverty,stiff tongue,etc.Conclusion Lurasidone has a favorable safety profile,and women need to closely monitor prolactin levels when taking this medication.The drug is relatively safe for use in pregnant,puerperal and perinatal women and patients with poor metabolic function.Hypoprolactinaemia and restless leg syndrome are new rare suspected adverse events with lurasidone.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective To explore the difference in efficacy of metoprolol versus ivabradine in the treatment of postural orthostatic tachycardia syndrome(POTS)in the elderly after COVID-19 infection.Methods A total of 110 patients diagnosed with POTS at our department from Decem-ber 1,2022 to January 31,2023 were included.According to their drug regimen,they were divided into metoprolol group(62 patients)and ivabradine group(48 patients).On the 28th day of out-patient follow-up,the resting heart rate,heart rate of 10 min of standing,symptom disappearance rate,hospitalization rate,and mortality rate were compared between the two groups.Results On the 28th day of treatment,the resting heart rate and postural heart rate for 10 min were decreased in both groups when compared with the levels at initial diagnosis(P＜0.01).And there were no significant differences in the two types of heart rate between the two groups on the 28th day(71.0±7.0 vs 72.1±7.0,P=0.401;76.5±7.2 vs 77.4±7.6,P=0.573).No obvious differences were observed between the two groups in symptom disappearance rate,hospitalization rate,or mortality rate(88.7％vs 89.6％,3.2％vs2.1％,0％vs 0％,P＞0.05).Conclusion Metoprolol and ivabradine can effectively treat POTS in the elderly patients after COVID-19 infection.