OBJECTIVE: To compare the protective effects of electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS) during pregnancy on maternal immune activation (MIA)-induced adverse pregnancy outcomes, fetal developmental defects, and neuropsychological behavior abnormalities in offspring mice. METHODS: Eighty pregnant C57BL/6 mice were randomly divided into 5 groups: control, model, EA, TEAS, and sham-stimulation groups, 16 mice in each group. MIA models were replicated on the day 12.5 of pregnancy via tail intravenous injection with polyinosinic-polycytidylic acid. On the second day of modeling success, in the EA and TEAS groups, the interventions were delivered at bilateral "Zusanli" (ST36), with a frequency of 2 Hz, a current of 0.5 mA, and for 20 min each day in the pregnant mice; and the interventions lasted 6 days. Body mass and fertility indexes of pregnant mice, and the development indexes of offspring mice were recorded. Liquid phase suspension chip technology was used to detect the levels of cytokines and chemotactic factors in the serum of pregnant mice and and fetal brain of offspring mice. Flow cytometry was adopted to detect the proportion of the subgroups and subtypes of spleen T lymphocytes and macrophages in pregnant mice. Using the open field test, prepulse inhibition (PPI) test and Morris water maze, the spatial learning and memory were assessed in offspring mice. Immunofluorescence staining was used to detect microglial count in the medial prefrontal cortex (mPFC) in offspring mice. RESULTS: Compared with the control group, the model group showed a reduced body mass of pregnancy mice (P<0.01), smaller litter size and fewer live births (P<0.01, P<0.05), the increase in dead birth and the decrease in offspring survival rate (P<0.05, P<0.01). When compared with model group, in the EA group and the TEAS group, the body mass of pregnancy mice rose (P<0.05), litter size and live births increased (P<0.05, P<0.01), the dead birth was reduced and the offspring survival rate higher (P<0.05). In comparison with the control group, the model group showed the increase in the levels of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), γ-interferon (IFN-γ) in the serum of pregnant mice, and spleen M1 macrophage proportion (P<0.01, P<0.05), and the decrease in spleen M2 macrophages of pregnant mice (P<0.01); and the increase in MCP-1 and IL-6 in fetal brain of offspring mice (P<0.05). Compared with the model group, the EA group and the TEAS group showed the decrease in MCP-1, IL-6 and IFN-γ, and spleen M1 macrophage proportion (P<0.01, P<0.05), and the increase in spleen M2 macrophages of pregnant mice (P<0.01, P<0.05) ; and the decrease in MCP-1 and IL-6 in fetal brain of offspring mice (P<0.05). Compared with the control group, in the model group, the total movement distance, escape incubation were extended (P<0.05, P<0.01), the frequency of entering the central area and crossing the platform decreased, and the activity duration in central area was shortened (P<0.05, P<0.01), the average speed rose (P<0.05), PPI%, the percentage of target quadrant swimming time in the total time and that of target quadrant swimming distance in the total distance were reduced (P<0.05, P<0.01) in offspring mice. When compared with the model group, in the EA group and TEAS group, the total movement distance and escape incubation were shortened, the average speed was reduced (P<0.05), PPI% and the frequency of crossing the platform increased (P<0.05, P<0.01); the percentage of target quadrant swimming time in the total time and that of target quadrant swimming distance in the total distance rose (P<0.05, P<0.01) in the offspring mice. In the EA group, the frequency of entering the central area and the activity duration in central area were higher (P<0.05, P<0.01); and in the the TEAS group, the activity duration in central area were longer (P<0.05). When compared with the control group, in the model group, microglial count in mPFC was elevated in offspring mice (P<0.05). In comparison with the model group, the EA group and the TEAS group showed the decrease of microglial count in mPFC (P<0.05). CONCLUSION EA and TEAS at "Zusanli" (ST36) during pregnancy effectively improve in the pregnancy outcomes and fetal brain developmental abnormalities induced by infection, and attenuate neurodevelopmental defects and mental disorders of offspring mice through inhibiting inflammatory activation of microglia in mPFC.
Animals ; Female ; Pregnancy ; Electroacupuncture ; Acupuncture Points ; Mice ; Mice, Inbred C57BL ; Humans ; Male

Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

Objective:To discuss the effect of DEAD-box RNA helicase 39A(DDX39A)gene silencing on the proliferation,migration and invasion of the esophageal cancer TE-1 cells,and to clarify its possible mechanism.Methods:For bioinformatics analysis,GSE63941,GSE77861,GSE20347,and GSE16153 chip data were downloaded from the GEO database.The esophagel cancer-related data were selected from the TCGA Database.R software was used to analyze the differentially expressed genes.STRING Database was used to construct the protein-protein interaction(PPI)network.Identification of key genes of high relevance was achieved using the MCODE plugin in Cytoscape.The expression of key genes in normal esophageal tissue and esophageal cancer tissue were analyzed with the GEPIA 2 database.Kaplan-Meier Plotter was used to perform survived analysis and plotting for the screened key genes.Cytological experiments were carried out on esophageal cancer TE-1 cells,and small interfering RNA(siRNA)technology was used to silence the expression of DDX39A gene.The TE-1 cells in the logarithmic growth phase were selected and divided into blank(MOCK)group,negative control(si-NC)group,and silencing(si-DDX39A)group.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the expression levels of DDX39A mRNA and protein in the TE-1 cells in various groups;CCK-8 assay was conducted to detect the proliferation activity of cells in various groups,and the cell scratch assay was used to measure the migration rate of cells in various groups;Transwell chamber assay was used to detect the number of invasion cells in various groups;Western blotting method was used to detect the expression levels of β-catenin,glycogen synthase kinase-3β(GSK3β),phosphorylated glycogen synthase kinase-3β(p-GSK3β),c-MYC,Cyclin D1 and nuclear β-catenin proteins in the cells in various groups.Results:Analyses using TCGA database combined with the GEO Database yielded a total of 56 differentially expressed genes.MCODE plugin in Cytoscape software identified 41 key genes of high relevance;DDX39A was screened by analyzing 41 genes through the GEPIA 2 and Kaplan-Meier plotter Databases.The results of RT-qPCR and Western blotting methods showed that compared with si-NC group,the expression levels of DDX39A mRNA and protein in the cells in si-DDX39A group were decreased(P＜0.05).The CCK-8 results showed that the proliferation activity of the cells in si-DDX39A group was lower than that in si-NC group(P＜0.05).The cell scratch assay results showed that the cell migration rate in si-DDX39A group after 24 h was lower than that in si-NC group(P＜0.05).The results of Transwell chamber assay showed that the number of invasion cells in si-DDX39A group was lower than that in si-NC group(P＜0.05).Compared with si-NC group,the expression levels of β-catenin,p-GSK3β,c-MYC,Cyclin D1,and nuclear β-catenin in the TE-1 cells in si-DDX39A-1 group and si-DDX39A-3 group were decreased(P＜0.01),but the expression levels of GSK3β protein had no significant differences(P＞0.05).Conclusion:Silencing of DDX39A gene could inhibit the proliferation,migration and invasion of TE-1 cells,and the mechanism may be related to the regulation of Wnt/β-catenin signaling pathway.

Objective To investigate the predictive value of perfusion imaging parameters of multi-slice spiral computed tomography (MSCT) for the poor prognosis in patients with osteonecrosis of the femoral head (ONFH). Methods A total of 118 patients with ONFH who were treated in a hospital from May 2022 to May 2023 were selected as the research subjects. All patients received 3D printing guide plate assisted with curettage of necrotic focus combined with ceramic rod implantation. According to the one-year follow-up results, patients were divided into a good prognosis group (n＝94) and a poor prognosis group (n＝24). Baseline data and MSCT perfusion imaging parameters (mean transit time [MTT], blood flow [BF], blood volume [BV]) were compared between the two groups. The correlations of MTT, BF and BV with the severity and prognosis of ONFH were analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of MSCT perfusion imaging parameters for the prognosis of ONFH patients. Results There were significant differences in the necrosis site, necrosis volume and Association Research Circulation Osseous (ARCO) staging between the two groups (P＜0.05). The MTT was shorter, BF was less and BV was less in the poor prognosis group than those in the good prognosis group (P＜0.001). MTT, BF and BV were negatively correlated with necrosis volume and ARCO staging (P＜0.001). Decreased MTT, BF, and BV were independent risk factors for poor prognosis in ONFH patients (P＜0.001). The AUC of the combination of these three parameters for predicting poor prognosis was 0.918, which was significantly better than that of independent parameter (P＜0.05). Conclusions The parameters of MSCT perfusion imaging are closely related to the condition and prognosis of ONFH patients, and are help of predicting the prognosis of ONFH patients.

Background: and Purpose This study aimed to determine the changes in cerebral blood flow (CBF) in patients who received different durations of hemodialysis (HD) using arterial spin labeling magnetic resonance imaging. Methods: The study included 46 patients who received HD and 24 demographically similar healthy controls (HCs). Patients who received HD were divided into three subgroups based on its duration: HD-1 (n=15, dialysis duration ≤24 months), HD-2 (n=16, dialysis duration >24 and ≤72 months), and HD-3 (n=15, dialysis duration ≥73 months). All subjects completed the Mini Mental State Examination and Montreal Cognitive Assessment tests, and the patients who received HD underwent laboratory tests. Group-level differences in the global and regional CBFs between patients who received HD and HCs were assessed. Correlation analysis was performed to evaluate the associations among CBF, clinical variables, and cognitive function. Results: Compared with HCs, global and regional CBFs were significantly increased in the HD-1 and HD-2 groups (p<0.05), but there was no significant difference in the HD-3 group (p>0.05). However, compared with the HD-1 group, the HD-3 group had significantly decreased global and regional CBFs (p<0.05). The cognitive function was worse in patients who received long-term HD than in HCs. Increased dialysis duration and hemoglobin level were predictive risk factors for decreased CBF in patients who received long-term HD. Conclusions Patients who received long-term HD with normal CBF had worse cognitive function, which may be related to increased dialysis duration.

Objective:To investigate the preoperative diagnostic value of 99Tc m-methoxyisobutylisonitrile (MIBI) planar imaging and SPECT/CT imaging for primary hyperparathyroidism (PHPT), and analyze the relevant factors affecting the imaging results. Methods:From June 2016 to September 2019, a total of 62 patients (15 males, 47 females, age range: 27-80 years) confirmed as PHPT by postsurgical pathology in Affiliated Hospital of Qingdao University were retrospectively enrolled. The diagnostic efficacies of 99Tc m-MIBI planar imaging and SPECT/CT imaging were compared using χ2 test. The differences of preoperative serum parathyroid hormone (PTH), Ca and the maximum diameter of lesion between the positive and negative groups of planar imaging were analyzed using independent-sample t test and Mann-Whitney U test. The region of interest (ROI) method was applied to calculate the uptake ratio of lesions to normal tissues at the early phase (T/Ne) and delayed phase (T/Nd) in positive cases of planar imaging. Pearson or Spearman correlation analysis was used to evaluate the correlation of T/Ne, T/Nd with preoperative serum PTH, Ca and the maximum diameter of lesion. The receiver operating characteristic (ROC) curves of preoperative serum PTH, Ca and positive planar imaging were drawn and the cut-off values were obtained. Results:The sensitivity of planar imaging and SPECT/CT imaging was 69.35%(43/62) and 87.10%(54/62) respectively ( χ2=5.729, P=0.017). The preoperative serum PTH, Ca levels and the maximum diameter of lesion in patients with positive planar imaging (253.32(107.00, 331.70) ng/L, 2.78(2.51, 2.87) mmol/L, (2.01±0.88) mm) were higher than those with negative planar imaging ((111.86±44.29) ng/L, (2.59±0.21) mmol/L, (1.42±0.55) mm; z values: -2.802, -1.978, t=3.300, all P<0.05). T/Ne was positively correlated with preoperative serum PTH ( rs=0.511, P<0.001) and the maximum diameter of lesion ( r=0.381, P=0.012), and T/Nd was positively correlated with preoperative serum PTH ( rs=0.538, P<0.001), Ca ( rs=0.348, P=0.022) and the maximum diameter of lesion ( r=0.463, P=0.002). The area under the ROC curve between preoperative serum PTH, Ca and planar imaging was 0.725 and 0.646, respectively. Preoperative serum PTH had a better predictive value with the optimal cut-off value of 150.4 ng/L. Conclusions:Preoperative serum PTH, Ca and the maximum diameter of lesion are positively correlated with 99Tc m-MIBI uptake in PHPT patients with positive planar imaging results. When preoperative serum PTH is lower than 150.4 ng/L, planar imaging is prone to false negative. SPECT/CT imaging has a significant value in preoperative diagnosis and the combination of PTH and CT can improve the positive rate.

Objective:To compare the consistency of artificial analysis and artificial intelligence analysis in the identification of fundus lesions in diabetic patients.Methods:A retrospective study. From May 2018 to May 2019, 1 053 consecutive diabetic patients (2 106 eyes) of the endocrinology department of the First Affiliated Hospital of Zhengzhou University were included in the study. Among them, 888 patients were males and 165 were females. They were 20-70 years old, with an average age of 53 years old. All patients were performed fundus imaging on diabetic Inspection by useing Japanese Kowa non-mydriatic fundus cameras. The artificial intelligence analysis of Shanggong's ophthalmology cloud network screening platform automatically detected diabetic retinopathy (DR) such as exudation, bleeding, and microaneurysms, and automatically classifies the image detection results according to the DR international staging standard. Manual analysis was performed by two attending physicians and reviewed by the chief physician to ensure the accuracy of manual analysis. When differences appeared between the analysis results of the two analysis methods, the manual analysis results shall be used as the standard. Consistency rate were calculated and compared. Consistency rate = (number of eyes with the same diagnosis result/total number of effective eyes collected) × 100%. Kappa consistency test was performed on the results of manual analysis and artificial intelligence analysis, 0.0≤ κ<0.2 was a very poor degree of consistency, 0.2≤ κ<0.4 meant poor consistency, 0.4≤ κ<0.6 meant medium consistency, and 0.6≤ κ<1.0 meant good consistency. Results:Among the 2 106 eyes, 64 eyes were excluded that cannot be identified by artificial intelligence due to serious illness, 2042 eyes were finally included in the analysis. The results of artificial analysis and artificial intelligence analysis were completely consistent with 1835 eyes, accounting for 89.86%. There were differences in analysis of 207 eyes, accounting for 10.14%. The main differences between the two are as follows: (1) Artificial intelligence analysis points Bleeding, oozing, and manual analysis of 96 eyes (96/2042, 4.70%); (2) Artificial intelligence analysis of drusen, and manual analysis of 71 eyes (71/2042, 3.48%); (3) Artificial intelligence analyzes normal or vitreous degeneration, while manual analysis of punctate exudation or hemorrhage or microaneurysms in 40 eyes (40/2042, 1.95%). The diagnostic rates for non-DR were 23.2% and 20.2%, respectively. The diagnostic rates for non-DR were 76.8% and 79.8%, respectively. The accuracy of artificial intelligence interpretation is 87.8%. The results of the Kappa consistency test showed that the diagnostic results of manual analysis and artificial intelligence analysis were moderately consistent ( κ=0.576, P<0.01). Conclusions:Manual analysis and artificial intelligence analysis showed moderate consistency in the diagnosis of fundus lesions in diabetic patients. The accuracy of artificial intelligence interpretation is 87.8%.

OBJECTIVE: To analyze the clinical features, biochemical characteristics and molecular pathogenesis of a girl with isovaleric acidemia. METHODS: Clinical features, blood spot amino acid profiles and urinary organic acid profiles of the patient were analyzed. Targeted capture, next generation sequencing and Sanger sequencing were carried out to detect potential variant of the IVD gene. RESULTS: The patient presented with poor weight gain, poor feeding, lethargy, and a "sweaty feet" odor 10 days after birth. Biochemical test suggested hyperammonemia. Blood spot amino acid profiles displayed a dramatic increase in isovalerylcarnitine (C5: 3. 044, reference range 0.04 - 0.4 μmol/L). Organic acid analysis of her urine sample revealed a high level of isovaleric glycine (669. 53, reference range 0 - 0.5). The child was ultimately diagnosed with isovaleric acidemia, and was found to harbor a paternally derived heterozygous variant c.149G>A (p.R50H) and a maternally derived heterozygous variant c.1123G>A (p.G375S) of the IVD gene. Her elder brother was a heterozygous carrier of c.1123G>A (p.G375S) variant. The c.149G>A (p.R50H) was a known pathogenic variant, while the c.1123G>A (p.G375S) variant was previously unreported. CONCLUSION The pathogenesis of the patient was delineated from the perspective of genetics, which has provided a basis for clinical diagnosis, treatment as well as genetic counseling.
Amino Acid Metabolism, Inborn Errors/genetics* ; Child ; Female ; Heterozygote ; Humans ; Isovaleryl-CoA Dehydrogenase/genetics* ; Male ; Mutation

Objective To develop a model of malignant risk prediction of solitary pulmonary nodules(SPN) with the metabolic characteristics of the lesion.Methods A total of 362 patients (291 malignant cases and 71 benign cases;194 males,168 females;median age:61 years) who underwent PET/CT imaging from January 2013 to July 2017 were analyzed.The diagnosis of malignant SPN was based on pathological results,and that of benign SPN was based on pathological or follow-up results.Differences of clinical/imaging characteristics in patients with benign and those with malignant SPN were analyzed.Risk factors were screened by multivariate non-conditional logistic regression analysis.The self-verification of the model was done by the receiver operating characteristic (ROC) curve analysis,out-of-group verification was performed by k-fold cross-validation.Results There were statistically significant differences in age,maximum standardized uptake value (SUVmax),size,lobulation,spiculation,pleural traction,vessel connection,calcification,vacuole,and emphysema between patients with benign and malignant nodules (all P＜0.05).The risk factors for malignant nodules included age,SUVmax,size,lobulation,calcification and vacuole.The odds ratio (OR) values (95％ CI) were 1.040(1.007-1.075),1.612(1.287-2.017),1.149(1.074-1.230),4.650(2.138-10.115),0.216(0.085-0.548),and 3.043(1.302-7.111),respectively.The logistic regression model was as follows:P=1/(1+e-x),x=-5.583+0.039×age+0.477×SUVmaxx+0.139×size+1.537×lobulation-1.532×calcification+ 1.1 13×vacuole.The estimated area under the curve (AUC) for the model was 0.915(95％ CI:0.883-0.947),sensitivity was 89.7％,specificity was 78.9％.K-fold cross-validation showed that the training accuracy was 0.899±0.011,the predictive accuracy was 0.873±0.053.Conclusions The risk factors for malignant nodules included age,SUVmax,size,lobulation,calcification and vacuole.After verification,the model has a satisfactory accuracy.It may help clinics make accurate decisions.

In recent decades, event-related potentials have been used for the clinical electrophysiological assessment of patients with disorders of consciousness (DOCs). In this paper, an oddball paradigm with two types of frequency-deviant stimulus (standard stimuli were pure tones of 1000 Hz; small deviant stimuli were pure tones of 1050 Hz; large deviant stimuli were pure tones of 1200 Hz) was applied to elicit mismatch negativity (MMN) in 30 patients with DOCs diagnosed using the JFK Coma Recovery Scale-Revised (CRS-R). The results showed that the peak amplitudes of MMN elicited by both large and small deviant stimuli were significantly different from baseline. In terms of the spatial properties of MMN, a significant interaction effect between conditions (small and large deviant stimuli) and electrode nodes was centered at the frontocentral area. Furthermore, correlation coefficients were calculated between MMN amplitudes and CRS-R scores for each electrode among all participants to generate topographic maps. Meanwhile, a significant negative correlation between the MMN amplitudes elicited by large deviant stimuli and the CRS-R scores was also found at the frontocentral area. In consequence, our results combine the above spatial properties of MMN in patients with DOCs, and provide a more precise location (frontocentral area) at which to evaluate the correlation between clinical electrophysiological assessment and the level of consciousness.
Acoustic Stimulation ; Adolescent ; Adult ; Aged ; Auditory Perception ; physiology ; Brain Injuries ; complications ; physiopathology ; Consciousness Disorders ; etiology ; physiopathology ; Electroencephalography ; Evoked Potentials ; Female ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Severity of Illness Index ; Wavelet Analysis