Objective To explore the mechanism of modified maimendong decoction (MMD) in inhibiting lung cancer metastasis from the perspective of immune regulation. Methods CTC-TJH-01 and LLC cells were intervened with different concentrations of modified maimendong decoction. The cell proliferation was detected with a CCK-8 kit, apoptosis was detected with an Annexin V-FITC/PI kit, and cell migration was detected through Transwell assays. A lung metastasis model was established through the tail vein injection of LLC cells into C57BL/6 mice, and body weight change and lung tumor metastasis in the mice were evaluated after continuous gavage intervention with MMD. HE staining, immunohistochemistry, and immunofluorescence were employed to observe the histomorphology, Ki-67 protein level, and NK and T cell levels of metastatic lesions. The levels of NK and T cells in the peripheral blood of mice were detected throughflow cytometry. Results MMD had no significant inhibitory effect on the proliferation, apoptosis, and migration of CTC-TJH-01 and LLC cells in vitro. In mice, MMD could significantly inhibit the lung metastasis of LLC cells, increase the proportion of NK and CD8⁺ T cells in peripheral blood and tumor microenvironment (P<0.05), and reduce the expression of Ki-67 protein in metastatic tumor tissues (P<0.05). Conclusion MMD may inhibit the growth of metastatic tumors by upregulating the expression levels of NK and CD8⁺ T cells in peripheral blood to promote the elimination of circulating tumor cells, and regulating the infiltration of NK and CD8⁺ T cells in the immune microenvironment of metastatic tumors, then play an antimetastatic role in lung cancer.

Hemiplegic migraine （HM） is a specific subtype of migraine with aura and is difficult to diagnose due to its low incidence rate and diverse clinical symptoms. This article reports a case of HM with hemiplegia as the initial presentation. This patient had a long course of disease and critical conditions and was comorbid with intractable epileptic seizures. A literature review is performed to improve the understanding of this disease among clinicians.
Stroke

Objective To investigate the effect of auditory brainstem response(ABR)in clinical detection and severity assessment of autism spectrum disorder(ASD)in children with normal hearing.Methods ① A total of 55 autistic children(110 ears)with normal hearing and 55 children(110 ears)with typical development(TD)who did not differ in sex composition ratio and average monthly age were divided into four sub-groups according to age:≤24 months group(22 ears),25～36 months group(40 ears),37～48 months group(28 ears)and＞48 months group(20 ears).The ABR latencies and interpeak latencies were compared between ASD children and age-matched TD children.② ASD children were graded by severity according to the Diagnostic and Statistical Manual of Mental Dis-orders(DSM-V),and the correlations between the ABR latencies and interpeak latencies in autistic children with normal hearing and the severity grading were studied.Results ① No statistically significant differences in ABR wave latencies and interpeak latencies were found in autistic children with normal hearing under 24 months of age compared to age-matched TD children(P＞0.05).② Compared with children with TD,autistic children with nor-mal hearing at 25～36 months of age had significantly longer wave Ⅲ latencies and the interpeak latencies of Ⅰ-Ⅲ andⅠ-Ⅴ;the significantly longer wave Ⅲ,Ⅴ latencies,the interpeak latencies of Ⅰ-Ⅲ,Ⅲ-Ⅴ and Ⅰ-Ⅴ in autistic chil-dren with normal hearing at 37～48 months of age.Autistic children with normal hearing in the＞48 months group had significantly longer wave Ⅴ latencies and interpeak latencies of Ⅲ-Ⅴ,Ⅰ-Ⅴ than age-matched TD children(P＜0.05).③ The higher the ASD severity grading the longer the wave Ⅲ and V latencies and the longer interpeak latencies of Ⅰ-Ⅲ,Ⅲ-Ⅴ,and Ⅰ-Ⅴ(P＜0.05).Conclusion Differences in the level of auditory brainstem pathway de-velopment emerged at 25 months of age,and autistic children with normal hearing had significantly lower levels of auditory brainstem development than age-matched TD children.There were correlations between the latencies and interpeak latencies of ABR in autistic children with normal hearing and the severity grading.

Objective:To compare demographic characteristics,clinical characteristics,therapeutic characteris-tics and physiological indicators of patients with bipolar Ⅰ disorder and bipolar Ⅱ disorder.Methods:A total of 381 patients with bipolar disorder(BD)diagnosed by the Diagnostic and Statistical Manual of Mental Disorders 5 th Edi-tion(DSM-5)were selected,including 302 patients with BD-Ⅰ(79.27％),74 patients with BD-Ⅱ(19.42％)and 5 patients with other specific and related disorders(1.31％).Demographic and clinical characteristics were collected with self-designed clinical information questionnaire.Multivariate logistic regression and multivariate linear regres-sion analysis were used for analysis.Results:Compared with patients with BD-Ⅱ,patients with BD-Ⅰ had more risk to have psychotic features(OR=5.75,95％CI:2.82-11.76),longer disease duration,and more repeated transcra-nial magnetic therapy(OR=3.09,95％CI:1.02-9.35),higher uric acid,total cholesterol and high-density lipo-protein.BD-Ⅰ in Han nationality was more common(OR=11.50,95％CI:1.76-75.30),and had lower education level(OR=10.22,95％CI:1.16-89.77),and less family history of psychosis(OR=2.34,95％CI:1.01-5.42).Conclusion:There are significant differences between BD-Ⅰ and BD-Ⅱ in demographic and clinical charac-teristics,treatment status,and physiological indicators,which could provide clues for exploring the pathogenesis of bipolar disorder.

Originating but free from chromosomal DNA, extrachromosomal circular DNAs (eccDNAs) are organized in circular form and have long been found in unicellular and multicellular eukaryotes. Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA, for which few detection methods are available. Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation, evolution, and drug resistance as well as aging, genomic diversity, and other biological processes, bringing it back to the research hotspot. Several mechanisms of eccDNA formation have been proposed, including the breakage-fusion-bridge (BFB) and translocation-deletion-amplification models. Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health. The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites. The present review summarized the research history, biogenesis, and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction. We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection, prognosis, and treatment of gynecologic tumors. This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.
Male ; Female ; Animals ; Humans ; Swine ; DNA, Circular/genetics* ; Genital Neoplasms, Female ; Semen ; DNA ; Reproduction

Objective:To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV).Methods:A prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance.Results:Eighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA ( F=50.298) gradually increased, CRT ( F=25.220), PED height ( F=144.16), SFCT ( F=69.77), LVCT ( F=136.69), CVI ( F=72.70) gradually decreased after treatment. The differences were statistically significant ( P<0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. Conclusion:Subretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.

Objective To evaluate the incidence of postoperative atrial fibrillation (POAF) after dexmedetomidine and diazepam in patients undergoing coronary artery bypass grafting (CABG). Methods A retrospective cohort study was conducted in the patients who underwent CABG in the General Hospital of Northern Theater Command from October 2020 to June 2021. By propensity score-matching method, the incidence of POAF after dexmedetomidine and diazepam application in patients undergoing CABG was evaluated. Results Finally 207 patients were collected, including 150 males and 57 females, with an average age of 62.02±8.38 years. Among the 207 patients, 53 were treated with dexmedetomidine and 154 with diazepam before operation. There was a statistical difference in the proportion of hypertension patients and smoking patients between the two groups before matching (P<0.05). According to the 1∶1 propensity score-matching method, there were 53 patients in each of the two groups, with no statistical difference between the two groups after matching. After matching, the incidence of POAF in the dexmedetomidine group was lower than that in the diazepam group [9.43% (5/53) vs. 30.19% (16/53), P=0.007]. There was no death in the two groups during hospitalization, and there was no statistical difference in the main adverse events after operation. The ICU stay (21.28±2.69 h vs. 22.80±2.56 h, P=0.004) and mechanical ventilation time (18.53±2.25 h vs. 19.85±2.01 h, P=0.002) in the dexmedetomidine group were shorter. Regression analysis showed that age, smoking and diabetes were related to the increased incidence of POAF (P<0.05), and preoperative use of dexmedetomidine was associated with a reduced incidence of POAF (P=0.002). Conclusion For patients undergoing CABG, the incidence of POAF with dexmedetomidine before operation is lower than that with diazepam. Preoperative application of dexmedetomidine is the protective factor for POAF, and old age, smoking and diabetes are the risk factors for POAF.

Objective To investigate the involvement of phosphofurin acidic cluster sorting protein-2(PACS-2)in mitochondrial function and apoptosis in N2a/APP695swe cells and further explore the role and significance of PACS-2 in the development of Alzheimer's disease(AD).Methods The CCK8 method was used to analyze the cell survival rate of N2a/APP695swe cells treated with different concentrations of tetrahydroxy stilbene glycoside(TSG)for 48h and to select the appropriate concentration of TSG for subsequent experiments.N2a/WT cells and N2a/APP695swe cells were routinely cultured in vitro,and the experimental cells were divided into 3 groups:blank control group(WT group):N2a/WT cells;model group(APP group):N2a/APP695swe cells;treatment group(TSG group):N2a/APP695swe cells with appropriate concentrations of TSG intervention.TUNEL method to observe apoptosis by fluorescence microscopy;JC-1 method for flow detection of cellular mitochondrial membrane potential;WB to detect protein expression of PACS-2;RT-qPCR to detect PACS-2 mRNA expression.Results CCK8 method was used to analyze the cell survival rate of different concentrations of TSG acting on cells after 48h:the protective effect of 100 μmol/L TSG was the most significant and the difference was statistically significant(P<0.01).The TUNEL method of fluorescence microscopy observed the apoptosis:compared with the WT group,the apoptosis rate of APP group was increased,compared with the APP group,the apoptosis rate of TSG group was decreased,and the differences were statistically significant(P<0.05).The JC-1 method was used to detect the mitochondrial membrane potential of cells:compared with the WT group,the membrane potential of APP group was decreased,compared with the APP group,the membrane potential of TSG group was increased,and the differences were statistically significant(P<0.05);Western blot(WB)detection of PACS-2 protein expression:compared with the WT group,PACS-2 expression was significantly higher in the APP group,and compared with the APP group,PACS-2 expression was significantly lower in the TSG group,with statistically significant differences(P<0.05);The RT-qPCR detected the mRNA expression of PACS-2:the expression of PACS-2 was elevated in the APP group compared with the WT group and decreased in the TSG group compared with the APP group,with statistically significant differences(P<0.05).Conclusion PACS-2 has an important role in the development of AD,and its upregulation may promote the development of AD.The cerebroprotective drug TSG may exert cytoprotective effects by downregulating PACS-2 to inhibit apoptosis and improve mitochondrial function in AD model cells.

BACKGROUND:Quercetin plays an important role in the proliferation and differentiation of bone marrow mesenchymal stem cells,but less research has been done on its mechanism of promoting the migration of bone marrow mesenchymal stem cells. OBJECTIVE:To study the effect of quercetin on the migration of human bone marrow mesenchymal stem cells through in vitro experiments,and to explore the regulatory role of CCR1 and CXCR4. METHODS:Human bone marrow mesenchymal stem cells were selected as experimental subjects.CCK8 assay was used to detect the effect of quercetin on the proliferative activity of human bone marrow mesenchymal stem cells.Cell scratch assay and Transwell assay were used to detect the in vitro invasive and migratory abilities of human bone marrow mesenchymal stem cells after quercetin treatment,respectively.The role of quercetin in relation to CCR1 and CXCR4 was demonstrated with the help of molecular docking technology.Western blot assay and real-time fluorescence quantitative PCR were used to detect the migration-related chemokine expression after quercetin treatment. RESULTS AND CONCLUSION:(1)5 and 10 μmol/L quercetin could significantly promote the proliferation of human bone marrow mesenchymal stem cells,and the drug concentration of 10 μmol/L resulted in the highest cell proliferation efficiency.(2)To better explore the dose-effect relationship of quercetin affecting the migration of human bone marrow mesenchymal stem cells,5 and 10 μmol/L quercetin were selected for the subsequent experiments,and ligustrazine was used as the positive control drug,and the experiments were divided into blank control group,5 μmol/L quercetin group,10 μmol/L quercetin group,and 100 μmol/L ligustrazine group.(3)In vitro migration and invasion ability of human bone marrow mesenchymal stem cells were elevated in a concentration-dependent manner after quercetin treatment,and the migration effect of 10 μmol/L quercetin group was better than that of ligustrazine group.(4)The molecular docking results suggested that there was a strong interaction between quercetin and CCR1 and CXCR4.(5)Quercetin could up-regulate the expression of CCR1 and CXCR4 proteins and mRNA.(6)This study confirmed at the cellular level that quercetin could promote the migration of human bone marrow mesenchymal stem cells by targeting CCR1 and CXCR4.

Objective:To evaluate the predictive value of 18F-FDG PET-based radiomics models for lymphovascular invasion (LVI) and visceral pleural invasion (VPI) in lung adenocarcinoma (LAC) prior to surgery. Methods:Eighty-seven patients with LAC (42 males, 45 females, age: (64.6±9.0) years; 90 lesions) pathologically confirmed in the Affiliated Taizhou People′s Hospital of Nanjing Medical University between August 2018 and August 2022 were retrospectively included. Based on the radiomics features extracted from PET images, the machine learning models were constructed by using the support vector machine (SVM), logical regression (LR), decision tree (DT), and K-nearest neighbor (KNN) algorithm. Stratified sampling (Python′s StratifiedkFold function) was employed to divide the data into training set and test set at a ratio of 8∶2. The model stability was assessed using the 50% discount cross-validation. The ROC curve was drawn, and the AUC was calculated to evaluate the value of radiomics models in predicting LVI and VPI in LAC. Delong test was used to compare AUCs of different models.Results:The radiomics models (SVM, LR, DT, KNN) based on PET images showed good predictive value for LVI and VPI in patients with LAC. For LVI, the AUCs were 0.91, 0.90, 0.91, 0.91 in the training set, and were 0.85, 0.87, 0.77, 0.78 in the test set; for VPI, the AUCs were 0.86, 0.86, 0.84, 0.81 in the training set, and were 0.82, 0.80, 0.69, 0.78 in the test set. The F1 scores of the SVM model were the best (0.59 and 0.66 for predicting LVI and VPI respectively). The Delong test showed that there were no significant differences in AUCs among the four models ( z values: from -1.46 to 1.71, all P>0.05). Conclusions:The machine learning models based on 18F-FDG PET radiomics features are effective in predicting LVI and VPI in patients with LAC prior to surgery. These models can assist clinicians in stratifying the risk of LAC and making informed clinical decisions. The SVM model has the best performance in predicting LVI and VPI.