Objective To establish a rat model of acute antibody-mediated rejection (AMR) in kidney transplantation and investigate the preventive effect of dihydroartemisinin (DHA) on acute AMR. Methods BN rats were used as donors and Lewis rats as recipients. Kidney transplantation was performed 2 weeks after skin transplantation for sensitization. After establishing the acute AMR model in rat kidney transplantation, the recipients of experimental groups included the syngeneic kidney transplantation group (6 rats), the allogeneic kidney transplantation group (6 rats), the syngeneic skin transplantation followed by kidney transplantation group (12 rats), and the allogeneic skin transplantation followed by kidney transplantation group (24 rats). The groups for investigating the preventive effect of DHA on acute AMR included the control group (allogeneic skin transplantation followed by kidney transplantation) and the DHA group (allogeneic skin transplantation followed by kidney transplantation + DHA), with 12 rats in each group. The survival time of recipient rats, serum donor-specific antibody (DSA) levels and graft pathological changes were used to identify the acute AMR model. On this basis, DSA levels, pathological changes in the transplant kidneys and peripheral blood B-cell levels were detected to assess the preventive effect of DHA on acute AMR. Results Compared with the allogeneic kidney transplantation group, skin transplantation sensitization significantly shortened the survival time of recipient rats (P<0.01). Compared with the syngeneic skin transplantation followed by kidney transplantation group, the allogeneic skin transplantation followed by kidney transplantation group showed significantly elevated serum DSA-IgG levels from 7 days after skin transplantation to 5 days after kidney transplantation (P<0.01), and significantly elevated DSA-IgM levels at 7 and 14 days after skin transplantation(all P<0.01). The transplant kidneys in the allogeneic skin transplantation followed by kidney transplantation group showed a small number of inflammatory cell infiltrations, tubular necrosis, capillaritis, and C4d deposition starting from 1 day after kidney transplantation, with these pathological changes worsening as the post-transplantation days increased. The kidney damage became significant starting from 3 days after transplantation. The above pathology manifestations were consistent with the characteristics of acute AMR. On the basis of establishing the acute AMR model, DHA treatment significantly prolonged the survival time of recipient rats (P<0.01) , and reduced serum DSA-IgG and DSA-IgM levels. DHA treatment significantly alleviated the pathological manifestations of acute AMR, including kidney damage, inflammatory cell infiltration, capillaritis and tubular necrosis, and also reduced C4d deposition in the transplant kidneys, inflammatory cell infiltration and peripheral blood CD19⁺ B-cell levels. Conclusions An acute AMR model is established by performing kidney transplantation 2 weeks after allogeneic skin transplantation in rats. It is discovered that DHA has immunosuppressive effects and may effectively prevent acute AMR, which provides a new strategy for the management of clinical AMR.

Depression is increasingly prevalent among adolescents and can profoundly impact their lives. However, the early detection of depression is often hindered by the time-consuming diagnostic process and the absence of objective biomarkers. In this study, we propose a novel approach for depression detection based on an affective brain-computer interface (aBCI) and the resting-state electroencephalogram (EEG). By fusing EEG features associated with both emotional and resting states, our method captures comprehensive depression-related information. The final depression detection model, derived through decision fusion with multiple independent models, further enhances detection efficacy. Our experiments involved 40 adolescents with depression and 40 matched controls. The proposed model achieved an accuracy of 86.54% on cross-validation and 88.20% on the independent test set, demonstrating the efficiency of multimodal fusion. In addition, further analysis revealed distinct brain activity patterns between the two groups across different modalities. These findings hold promise for new directions in depression detection and intervention.
Humans ; Male ; Female ; Adolescent ; Case-Control Studies ; Depression/diagnosis* ; Early Diagnosis ; Rest ; Electroencephalography/methods* ; Brain-Computer Interfaces ; Models, Psychological ; Reproducibility of Results ; Affect/physiology* ; Photic Stimulation/methods* ; Video Recording ; Brain/physiopathology*

Etiological research is necessary for understanding the occurrence and epidemiological patterns of diseases, and is also a prerequisite for the diagnosis, prevention and treatment of clinical diseases. Mendelian randomization(MR), a method of research that combines genetics and epidemiology, has the advantage of exploring the causal relationship between exposure and disease genetically as well as avoiding confounding factors and reverse causation. Thus, it has been extensively utilized in the etiological study of diseases. This paper reviews the implementation of MR in the research of ocular diseases and provides ideas and approaches for the investigation of related mechanisms as well as the development of intervention strategies.

Objective:To discuss the protective effect of gingerone on the hippocampal neuron HT22 cells after oxygen-glucose deprivation/reoxygenation(OGD/R),and to clarify the related mechanism.Methods:The HT22 cells were cultured,and the OGD/R cell injury model was established by setting the gradient of OGD/R time.The HT22 cells were divided into control group,OGD/R group,OGD/R+ 1 μmol·L-1 gingerone group,OGD/R + 10 μmol·L-1 gingerone group,OGD/R+100 μmol·L-1 gingerone group,and OGD/R+0.2%dimethyl sulfoxide(DMSO)group.The viability of the cells in various groups was detected by CCK-8 assay;the survival rates of the cells in various groups were calculated to determine the optimal drug concentration of gingerone.The cells were divided into control,OGD/R group,OGD/R+ gingerone,and OGD/R+gingerone+nuclear factor erythroid-2-related factor 2(Nrf2)inhibitor(ML385)groups.The cells in OGD/R + gingerone group were treated with gingerone for 4 h before OGD treatment for 8 h followed by reoxygenation for 8 h,and the cells in OGD/R+gingerone+ ML385 group were treated with 10 μmol·L-1 ML385 for 6 h before gingerone treatment.The viability of the cells in various groups was detected by CCK-8 assay;the expression levels of Nrf2,heme oxygenase-1(HO-1),B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax)proteins in the cells in various groups were detected by Western blotting method;the activity of superoxide dismutase(SOD)and the level of malondialdehyde(MDA)in the cell culture supernatant in various groups were detected by enzyme-linked immunosorbent assay(ELISA)method.Results:Compared with control group,the survival rate of the HT22 cells was below 50%after treated with OGD for 8 h and reoxygenation for 8 h,so the HT22 cell OGD/R model was established by treated with OGD for 8 h and reoxygenation for 8 h.Compared with OGD/R group,the survival rates of the cells in OGD/R+different doses of gingerone groups were increased to various extents,and the survival rate of the cells in OGD/R+ 100 μmol·L-1 gingerone group was significantly increased(P<0.01);so 100 μmol·L-1 gingerone was used for the subsequent experiment.Compared with control group,the viability of the cells in OGD/R group was significantly decreased(P<0.01),and the expression levels of Nrf2,HO-1,and Bax proteins in the cells were significantly increased(P<0.01),while the expression level of Bcl-2 protein in the cells was significantly decreased(P<0.05),and the SOD activity in the cell culture supernatant was significantly decreased(P<0.01),and the level of MDA was significantly increased(P<0.01);compared with OGD/R group,the viability of the cells in OGD/R + gingerone group was significantly increased(P<0.01),and the expression levels of Nrf2,HO-1,and Bcl-2 proteins in the cells were significantly increased(P<0.05 or P<0.01),while the expression level of Bax protein in the cells was decreased(P<0.05),the SOD activity in the cell culture supernatant was significantly increased(P<0.01),and the level of MDA was significantly decreased(P<0.01);compared with OGD/R + gingerone group,the viability of the cells in OGD/R + gingerone + ML385 group was significantly decreased(P<0.01),and the expression levels of Nrf2,HO-1,and Bcl-2 proteins were significantly decreased(P<0.01),while the expression level of Bax protein in the cells was significantly increased(P<0.01),the SOD activity in the cell culture supernatant was significantly decreased(P<0.01),and the level of MDA was significantly increased(P<0.05).Conclusion:Gingerone alleviates the oxidative stress damage,and thereby plays an inhibiory effect on the apoptosis of the HT22 neurons by activating the Nrf2/HO-1 signaling pathway after OGD/R.

Islelet transplantation (IT) is an ideal treatment for type 1 diabetes. However, a large number of transplanted islet cells become lost due to immune responses and other reasons, resulting in a poor long-term efficacy of IT. Islet encapsulation is wrapping islet cells with semi-permeable materials for protecting insulin secretion function by islet cells, reducing islet cell apoptosis and minimizing immune responses. Nanotechnology enables a nanoscale control of encapsulated materials. A better "isolation" of islet cells and external environment is essential for prolonging the survival time of islet cells. This review summarized the advantages and disadvantages of different nanotechnologies in encapsulating IT for the goals of prolonging the survival of islet cells, improving insulin secretion and boosting the efficacy of IT.

Cancer genomics has led to the discovery of numerous oncogenes and tumor suppressor genes that play critical roles in cancer development and progression.Oncogenes promote cell growth and proliferation,whereas tumor suppressor genes inhibit cell growth and division.The dysregulation of these genes can lead to the development of cancer.Recent studies have focused on non-coding RNAs(ncRNAs),including circular RNA(circRNA),long non-coding RNA(lncRNA),and microRNA(miRNA),as therapeutic targets for cancer.In this article,we discuss the oncogenes and tumor suppressor genes of ncRNAs associated with different types of cancer and their potential as therapeutic targets.Here,we highlight the mechanisms of action of these genes and their clinical applications in cancer treatment.Understanding the molecular mechanisms underlying cancer development and identifying specific therapeutic targets are essential steps towards the development of effective cancer treatments.

OBJECTIVES: To investigate the expression of cartilage acidic protein 1 (CRTAC1) in gastric cancer (GC) and its effect on biological behaviors and immune cell infiltration of GC. METHODS: Transcriptomic, GO and KEGG analyses were conducted to investigate the association of CRTAC1 expression with prognosis of GC patients and its involvement in cell function and signaling pathways. ESTIMATE algorithm was used to analyze the effect of CRTAC1 expression on the tumor microenvironment and the tumor mutation load. In two GC cell clines (HGC-27 and MKN-74), CCK8, EdU and clone formation assays, flow cytometry, and Hoechst staining were used to examine the effects of CRTAC1 knockdown on cell proliferation, cell cycle changes and apoptosis. Wound healing assay, Transwell assay, and Western blotting were performed to analyze the effect of CRTAC1 knockdown on GC cell migration and the underlying mechanism. RESULTS: Bioinformatics analysis showed significantly higher expression of CRTAC1 in GC tissues than in adjacent tissues (P<0.05). Age and tumor stage were both prognostic risk factors in GC patients with high CRTAC1 expression (P<0.001). Analysis using ESTIMATE algorithm showed that CRTAC1 expression increased immune cell infiltration and decreased tumor mutational load in GC (P<0.001). In HGC-27 and MKN-74 cells, CRTAC1 knockdown significantly inhibited cell proliferation and migration and promoted cell apoptosis. Western blotting demonstrated that CRTAC1 knockdown significantly increased E-cadherin expression and reduced the expression levels of vimentin, p-PI3K, AKT2, p-AKT and p-mTOR in GC cells. CONCLUSIONS High expression of CRTAC1 in GC tissues affects immunotherapeutic efficacy and prognosis of the patients, possibly by promoting epithelial-mesenchymal transition via modulating tumor mutational load, tumor microenvironment, and the PI3K/AKT signaling pathway.
Stomach Neoplasms/metabolism* ; Humans ; Cell Proliferation ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction ; Cell Movement ; Cell Line, Tumor ; Prognosis ; Apoptosis ; Tumor Microenvironment ; Female ; Male ; Epithelial-Mesenchymal Transition/genetics*

Objective To establish an animal model of postmortem redistribution of amantadine,and to study its postmortem redistribution in rats,so as to provide experimental evidence for forensic identification.Methods One hundred and twenty-six male SD rats were randomly divided into 3 groups and subjected to intragastric administration according to the maximum dose of treatment(L),LD50(M)and 2LD50(H).Those who did not die were killed according to the average time of death of LD50.Heart-blood,peripheral blood,heart,liver,spleen,lung,kidney,brain,muscle and testis were collected at 0 h,6 h,12 h,24 h,48 h,72 h and 96 h after death,and amantadine content was detected.Results For the rats in the L group,the concentration of amantadine decreased within 6 h after death and then increased in the heart-blood,heart and liver,unchanged within 48 h and reached the peak at 96 h in the spleen,kidney,brain,muscle and testis,while decreased in the lung.For the rats in the M group,the concentration of amantadine decreased within 24 h after death and then increased in all samples,and it reached the peak at 48 h after death in the peripheral blood,spleen,kidney and muscle tissues,at 72 h after death in the heart-blood and testis,and at 96 h after death in the liver,lung and brain tissues.For the rats in the H group,the concentration of amantadine showed a downward trend within 12 h after death in the heart and liver tissue,showed a downward trend within 48 h after death in the lung,brain and muscle tissue,and reached the peak at 96 h after death in the heart,liver,spleen,muscle and testicle tissues.Conclusion The postmortem redistribution was found in amantadine poisoning dead rats,which could provide experimental evidence for the forensic identification of death cases caused by amantadine poisoning.

Objective:To evaluate the relationship between preoperative serum cystatin C (Cys C) concentration and postoperative delirium (POD) in the patients.Methods:Three hundred and ninety patients, aged >50 yr, of American Society of Anesthesiologists Physical Status classification Ⅰor Ⅱ, scheduled for elective knee and hip replacement under combined spinal-epidural anesthesia, with Mini-Mental State Examination scores >23 at 1 day before operation, were included in the study. Peripheral blood samples were collected before operation, and the serum Cys C concentration was measured by the latex-enhanced immunoturbidimetric assay. The cerebrospinal fluid (CSF) 2 ml was collected after successful spinal-epidural puncture for determination of amyloid-β 42 (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau) concentrations by enzyme-linked immunosorbent assay. The patients were divided into POD group and non-POD group according to whether POD occurred. The logistic regression analysis was used to identify the risk and protective factors for POD, and the mediating effect of CSF biomarkers was analyzed. The receiver operating characteristic curve was drawn to evaluate the accuracy of serum Cys C concentration and combination of serum Cys C conceatration and CSF biomarker concentration in predicting POD.Results:Three hundred and twenty-seven patients were finally enrolled, and the incidence of POD was 13.5%. The results of logistic regression showed that increased serum Cys C concentration and increased concentrations of P-tau and T-tau in CSF were risk factors for POD, while increased concentration of Aβ42 and increased Aβ42/P-tau ratio and Aβ42/T-tau ratio in CSF were protective factors for POD ( P<0.05) after adjusting for multiple confounding variables such as age, sex, years of education, Mini-Mental State Examination score, smoking history, drinking history, hypertension and diabetes history. The mediation analysis showed that the relationship between serum Cys C concentration and POD was mediated by T-tau concentration in CSF (11.1%) and by Aβ42/T-tau ratio in CSF (18.0%). The area under the receiver operating characteristic curve of serum Cys C and CSF biomarker concentrations in predicting POD was 0.807 ( P<0.001). Conclusions:Increase in preoperative serum Cys C concentration is a risk factor for POD. T-tau concentration and Aβ42/T-tau ratio in CSF serve as the key mediators in the relationship between preoperative serum Cys C concentration and POD.

Objective : To explore the effects of Er: YAG laser irrigation technology on smear layer removal and dentin microhardness. Methods : A total of 102 ex vivo premolars were selected to amputate the crown , leaving a root length of 13 mm , after mechanical preparation , there were divided into experimental group (3% sodium hypochlorite , 3% NaOCl) and control group (0. 9% sodium chloride solution , NS) , and received syringe , ultrasound and Er: YAG laser terminal irrigation , which were specifically grouped into NaOCl + syringe , NaOCl + ultrasound , NaOCl + laser, NS + syringe , NS + ultrasound and NS + laser groups ( n = 17 ) . Scanning electron microscopy (SEM) evaluated smear layer removal from the upper, middle and apical parts of the root. The Vickers microhardness tester measured the microhardness before and after irrigation. Results : The NaOCl + laser group had the best effect on removing the root canal smear layer, and the amplitude of reducing the microhardness of dentin was the largest. There was no significant difference in the reduction of microhardness compared with the NaOCl + ultrasonic group (P > 0. 05) . Conclusion Er: YAG laser⁃activated NaOCl solution improves the clearance of the smear layer and reduced the microhardness of dentin.