Objective: To evaluate the performance of 5T magnetic resonance imaging (MRI) in visualizing dental pulp and periodontal ligament (PDL) tissues in vivo in the young adult population, thereby providing a basis for the application of high-field MRI technology in clinical oral examinations. Methods: The study was approved by the Ethics Committee of the hospital. A total of 15 healthy volunteers (413 permanent teeth altogether) were recruited and underwent full-mouth 5T MRI scans. Among them, six volunteers (168 permanent teeth) also received both 3T MRI and cone-beam computed tomography (CBCT) scans. Two dental specialists independently evaluated the imaging quality of the dental pulp and PDL on the images using a 5-point Likert scale and recorded the number of detectable root canals for each tooth. Inter-rater agreement was assessed using weighted kappa statistics and intraclass correlation coefficient (ICC). Non-parametric tests were employed to compare differences in imaging performance among different tissue structures, tooth positions, and imaging modalities. Results: 5T MRI can achieve in vivo imaging for most dental pulp tissues and partial periodontal membrane structures. There was a high level of agreement between the two raters in their imaging scores for the dental pulp and PDL (dental pulp κ = 0.934, PDL κ = 0.737). The imaging scores for dental pulp were significantly higher than those for PDL (P < 0.001), and the scores for molar dental pulp were lower than those for premolars and anterior teeth. In the multimodal comparison involving six volunteers, the raters showed good consistency in scoring dental pulp and PDL imaging across 5T MRI, 3T MRI, and CBCT, as well as in root canal counts (5T MRI for dental pulp κ = 0.971, 3T MRI for dental pulp κ = 0.933, CBCT for dental pulp κ = 0.964; 5T MRI for PDL κ = 0.625, 3T MRI for PDL κ = 0.667, CBCT for PDL κ = 0.571; ICC for root canal counts all ≥ 0.990). The imaging scores for dental pulp and PDL using 5T MRI were significantly higher than those using 3T MRI (dental pulp: P < 0.001; PDL: P = 0.022), but there was no statistically significant difference in the detection rate of the number of root canals between the two (P > 0.05). Although the imaging scores for dental pulp and PDL as well as the detection rate of the number of root canals with 5T MRI were inferior to those with CBCT (dental pulp: P < 0.001; PDL: P = 0.02; number of root canals: P < 0.05), 5T MRI can truly achieve "direct imaging" of these two soft tissues. Conclusion 5T MRI enables effective in vivo direct imaging of dental pulp and PDL tissues in the young adult population, indicating its potential clinical application value in the diagnosis and treatment of pulp and periodontal diseases.

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO ^+/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1^mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

Objective: To investigate the value of decreased carbohydrate antigen 19-9(CA19-9) kinetics in predicting short-term outcomes and determining prognosis among advanced biliary or pancreatic cancer patients receiving first-or second-line therapy in the real world. Methods : Eighty-nine patients were retrospectively collected with advanced biliary or pancreatic cancer, especially on the CA19-9 dynamics and decline rates at different time points. This study evaluated the association of CA19-9 changes with clinicopathological features, short-term response to antitumor therapy, and survival outcomes. Results : The enrolled patients recorded baseline CA19-9 levels ranging from 1.20 to 65 706.40 U/ml, with a median of 303.11 U/ml. There was no statistical correlation between baseline CA19-9 levels and gender, age, body mass index, primary tumor site, hepatic metastases, pulmonary metastases, lymph node metastases, peritoneal metastases, performance status, treatment lines, and combinations of drug types. Baseline CA19-9 levels were not associated with systemic immunoinflammatory index, prognostic nutritional index, and total bilirubin. A 25% or 50% decrease in CA19-9 after 2-3 therapy courses indicated short-term efficacy in reaching tumor objective remission or disease control. Both combinations of multiple drug types and a 25% decline in CA19-9 after one course of treatment were independent prognostic factors that affected the longer progression-free survival of patients receiving first or second line of treatment. Conclusion Decreased CA19-9 kinetics has specific values in predicting the efficacy and prognosis of advanced biliary or pancreatic cancer.

Objective:To investigate the relationship between oxygen consumption (VO 2), carbon dioxide production (VCO 2), and Oxygen Consumption/lactate (VO 2/Lac) with risk of death in patients with severe ARDS. Methods:A retrospective cohort study method was used, and the study subjects were hospitalized for >5 days adult patients with severe ARDS in the central intensive care unit of Henan Provincial People's Hospital from 1 March 2020 to 30 June 2023. The following patients were excluded: IC test was not completed on the 4th day of ICU admission, IC test results were unreliable, mechanical ventilation duration had exceeded 48 h at the time of ICU transfer or admission, palliative care patients and pregnant and parturient women. Using indirect calorimetry to determine VO 2 and VCO 2 values on the 4th day of admission, reviewing medical records to obtain general condition, disease information, blood gas analysis (including lactate value), diagnostic and therapeutic measures, and following up deaths by telephone and time of death. The primary outcome measure was death at 90 days, and the secondary outcome measure was death at 28 days, length of stay in ICU, total length of stay, and total hospitalization cost. Cox regression analysis and linear regression analysis were used to investigate the relationship between VO 2, VCO 2, VO 2/Lac and primary and secondary outcome indexes. Results:A total of 216 patients were enrolled, 78 patients (36.1%) died and 138 patients (63.9%) survived at 90 days. After correction for confounders, the results of multifactorial Cox regression analysis suggested that compared with the Q4 group, HR (95% CI) for 90-day risk of death in the VO 2 Q1 and Q2 groups was 3.21 (1.38, 7.49) and 3.24 (1.42, 7.38), and HR (95% CI) for 90-day risk of death in the VCO 2 Q1, Q2 and Q3 groups was 5.88 (2.33, 14.84), 4.26 (1. 60, 11.34) and 3.54 (1.34, 9.35), respectively, and the HR (95% CI) for 90-day risk of death in the VO 2/Lac Q1, Q2 and Q3 groups were 8.72 (3.01, 25.25), 8.43 (2.91, 24.47) and 4.04 (1.34, 12.17) respectively. P-trends were all <0.05, indicating that VO 2, VCO 2 and VO 2/Lac were linearly and negatively associated with the risk of 90-day mortality. In addition, VO 2, VCO 2, and VO 2/Lac were negatively associated with 28-day risk of death and higher VO 2/Lac was negatively associated with length of ICU stay. Conclusions:VO 2, VCO 2 and VO 2/Lac were negatively associated with 90-day mortality risk and 28-day mortality risk in patients with severe ARDS and may be independent risk factors predicting mortality risk of such patients.

Objective To investigate the effects of gypenoside(Gyp)on proliferation,migration and invasion of hu-man prostate cancer cell line PC-3.Methods PC-3 cells were treated with 200-1 200 μg/mL Gyp to determine the optimal concentration.PC-3 cells were divided into control,Gyp-L group(400 μg/mL),Gyp-M group(600 μg/mL)and Gyp-H group(800 μg/mL),and Gyp-H+8-bromo-cAMP group(100 μmol/L PKA activator).Colony formation assay was applied to detect cell proliferation.Apoptosis was measured by flow cytometry.Scratch experiment was applied to detect the migration ability.Transwell assay was applied to detect the invasive ability.ELISA experiment was applied to detect cAMP level in each group.Western blot was applied to detect the expres-sion of E-cadherin,N-cadherin,Snail,PKA and CREB proteins.Results Gyp inhibited PC-3 proliferation in a concentration dependent manner.Gyp concentration of 400,600 and 800 μg/mL was selected for subsequent experiments.Compared with the control group,colony formation,number of invasive cells,scratch healing rate,the levels of Snail,N-cadherin,PKA,cAMP,and CREB proteins in the Gyp-L,Gyp-M,and Gyp-H groups were significantly reduced(P＜0.05),but the apoptosis rate as well as the level of E-cadherin protein were significantly increased(P＜0.05).PKA activator attenuated the inhibitory effect of Gyp on the malignant behavior of prostate cancer cells.Conclusions Gyp inhibits proliferation,migration and invasion,and promotes apoptosis in prostate cancer cell line PC-3.

Neurological diseases are characterized by high rates of disability, mortality, recurrence, and prolonged disease courses, making Neurological Intensive Care Unit patients vulnerable during the transition phase to risks such as downgraded monitoring and reduced treatment and nursing support. These factors contribute to higher rates of unplanned ICU readmission, decreased patient satisfaction, and reduced quality of life. Effective transitional care can reduce adverse events and improve clinical outcomes. This article introduces the relevant concepts of transitional care for Neurological Intensive Care Unit patients, summarizes domestic and international transitional care models, and explores the application outcomes of these models to provide guidance and support for transitional care practices in Neurological Intensive Care Unit patients.

BACKGROUND:Casein kinase 2 binding protein 1 (CKIP-1) is an important negative control gene in bone formation.After the deletion of this gene,the overall bone of mice was significantly enhanced,and bone formation and bone density were significantly increased.microRNA (miRNA) as the early found small molecular regulator has a regulatory effect on most of the coding genes and plays an important role in osteogenic differentiation.OBJECTIVE:To investigate the effect and molecular mechanism of miRNA/CKIP-1 axis on osteogenic differentiation of bone marrow mesenchymal stem cells from osteoporosis patients.METHODS:The miRNA-Seq technology was used to detect the changes of miRNA in bone marrow mesenchymal stem cells in 32 patients with osteoporosis treated in the Department of Orthopedics,Kaifeng Central Hospital from March to June 2022 and healthy people in the physical examination center during the same period.The Targetscan website was used to predict the miRNA targeted to regulate CKIP-1.Luciferase reporter gene assay was used to detect the binding of miRNA and CKIP-1 promoter DNA.miR-192-5p analogs (miR-192-5p mimics)/negative control (NC mimics) or miR-192-5p inhibitors (miR-192-5p inhibitor)/negative control (NC inhibitor) were transfected in bone marrow mesenchymal stem cells.On days 7 and 14 after osteogenic induction,the expression levels of Runt-related transcription factor 2 (Runx2),osteocalcin,anti-osteopontin,bone sialoprotein,and CKIP-1,and the differentiation of bone marrow mesenchymal stem cells into osteoblasts were detected by real-time fluorescence quantitative PCR and alizarin red staining.The regulatory effect of miR-192-5p/CKIP-1/axis on osteogenic differentiation of cells was detected by western blot assay and alizarin red staining.RESULTS AND CONCLUSION:Compared with the healthy group,the expression levels of 16 miRNAs were significantly up-regulated and those of 53 miRNAs were significantly down-regulated in the osteoporosis group (P<0.05).Using Targetscan website and verified by luciferase reporter gene experiment,it was found that miR-192-5p and CKIP-1 had complementary nucleotide sequences (P<0.05).Overexpression of miR-192-5p significantly increased the expression levels of Runx2,osteocalcin,osteopontin,and bone sialoprotein (P<0.05),and inhibition of miR-192-5p significantly decreased the expression levels of Runx2,osteocalcin,osteopontin,and bone sialoprotein (P<0.05).After silencing the expression of CKIP-1,the protein levels of Runx2,osteocalcin,and osteopontin increased (P<0.05);the inhibitory effect of knockdown of miR-192-5p on osteogenic differentiation of cells was reversed.Above results confirm that the expression of miR-192-5p is decreased in osteoporosis.miR-192-5p promotes osteogenic differentiation of bone marrow mesenchymal stem cells by targeting the inhibition of CKIP-1 expression.

OBJECTIVE To explore the mechanism by which Gongfa Static Training regulates mitophagy through the PTEN-in-duced kinase 1(PINK1)/Parkin pathway in skeletal muscle insulin resistance in type 2 diabetes mellitus(T2DM).METHODS T2DM mouse model was established using a high-fat diet combined with streptozotocin(STZ)intraperitoneal injection.Mice were ran-domly divided into a model group,a metformin group,an aerobic exercise group,and a Gongfa Static Training group.The intervention effects of Gongfa Static Training were evaluated by measuring fasting blood glucose,Homeostatic Model Assessment of Insulin Resist-ance(HOMA-IR),glycated hemoglobin(HbA1c),lipid metabolism indicators,mitochondrial function in the gastrocnemius muscle,and the expression of PINK1 and Parkin-related genes and proteins.RESULTS Gongfa Static Training significantly reduced fasting blood glucose,HbA1c,and insulin resistance index in T2DM mice,improved lipid metabolism,and enhanced insulin sensitivity.It improved the structure and function of mitochondria in the gastrocnemius muscle by upregulating the mRNA and protein expression of PINK1 and Parkin.CONCLUSION Gongfa Static Training improves mitochondrial function and insulin resistance in the skeletal muscle of T2DM mice by regulating the PINK1/Parkin pathway.

Trichinella spiralis zinc metalloproteinase NAS-36 gene(TsNas36)is a member of the zinc metalloproteinase family found in excretory secretory products(ESP)of T.spiralis.In this study,TsNas36 gene was cloned and expressed,and its biological characteristics and temporal and spatial characteristics were identified.These results provide a theoretical and material basis for ex-ploring the biological function of TsNas36 gene.Bioinformatics analysis showed that TsNas36 was 470 amino acids(AA)in length with a molecular weight of about 54.69 kDa,no transmembrane region,and contained a signal peptide(1-20 AA),an Astacins domain(116-320 AA)and a CUB domain(355-470 AA).There were five active site residues located at amino acids 216(His),217(Glu),220(His),226(His)and 275(Tyr).The expression plasmid pET-28a(+)/TsNas36 was constructed and induced to express in E.coli BL21(DE3)to obtain the recombinant protein rTs-Nas36.The recombinant protein was used to immunize rabbits to obtain anti-rTsNas36 polyclonal antibody serum.Indirect ELISA results showed that the antibody titer reached 1∶105.qRT-PCR and Western blot results showed that the transcription levels of TsNas36 were significantly higher in newborn larvae(NBL)than in adult worm(AW)and muscle larva(ML)stages.Immunofluo-rescence results showed that TsNas36 was only localized in the epidermis of NBL.In summary,this study characterized the biological characteristics of the TsNas36 gene and found that this gene is highly period-specific and may be involved in the unique developmental process of NBL.