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.

The "Top 10 drug tips for the public in 2023" issued by the Chinese Pharmaceutical Association emphasizes the importance of drinking water correctly to the safety and efficacy of drugs. Each drug has an optimal amount of drinking water, and only the appropriate amount can ensure the efficacy and avoid adverse reactions. According to UpToDate clinical consultant, Micromedex, MCDEX evidence-based databases and the drug labels of the US FDA and the European Medicines Agency, a total of 164 drugs in 20 categories, including drugs for metabolism and endocrine system, anti-infective drugs, anti-tumor drugs, etc., were labeled with the recommendation of adequate water intake. Here we summarize the above-mentioned drugs and their recommended water intake. The common reasons to drink enough water include preventing esophageal and gastric injury, preventing kidney injury, preventing dehydration, water and electrolyte disorders, preventing constipation, reducing bladder toxicity, reducing radiation damage, and promoting stone discharge. In addition, different people have different requirements for the amount of water when taking medicine. Mastering the correct amount of water is conducive to controlling the disease and reducing the adverse drug events.

The "Top 10 drug tips for the public in 2023" issued by the Chinese Pharmaceutical Association emphasizes the importance of drinking water correctly to the safety and efficacy of drugs. Each drug has an optimal amount of drinking water, and only the appropriate amount can ensure the efficacy and avoid adverse reactions. According to UpToDate clinical consultant, Micromedex, MCDEX evidence-based databases and the drug labels of the US FDA and the European Medicines Agency, a total of 164 drugs in 20 categories, including drugs for metabolism and endocrine system, anti-infective drugs, anti-tumor drugs, etc., were labeled with the recommendation of adequate water intake. Here we summarize the above-mentioned drugs and their recommended water intake. The common reasons to drink enough water include preventing esophageal and gastric injury, preventing kidney injury, preventing dehydration, water and electrolyte disorders, preventing constipation, reducing bladder toxicity, reducing radiation damage, and promoting stone discharge. In addition, different people have different requirements for the amount of water when taking medicine. Mastering the correct amount of water is conducive to controlling the disease and reducing the adverse drug events.

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.

Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic disorder characterized by the development of hamartomas in the brain, heart, skin, kidney, lung, retina, and so on. One fetus from family 1 had a cardiac rhabdomyoma from 21 weeks and 6 days of gestational age, and developed multiple rhabdomyomas and tubers in the brain at 23 weeks and 5 days. The counter monozygotic twin fetus remained negative throughout the pregnancy according to imaging examination. A nonsense mutation in TSC2 (c.4762C>T, p.Gln1588*) was identified in both twins, but not in the mother. Family 2 was one pair of twin fetuses caused by a microdeletion of exon 30 within TSC2 inherited from their apparently asymptomatic mother with mosaic status. The larger fetus was identified as having the first cardiac rhabdomyoma from 17 weeks and 4 days of gestational age. The smaller fetus developed multiple rhabdomyomas until 25 weeks and 6 days of gestational age. Both families terminated the pregnancy. Here, we provide intrauterine examples of clinical variability among monozygotic twins suffering from TSC.

Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic disorder characterized by the development of hamartomas in the brain, heart, skin, kidney, lung, retina, and so on. One fetus from family 1 had a cardiac rhabdomyoma from 21 weeks and 6 days of gestational age, and developed multiple rhabdomyomas and tubers in the brain at 23 weeks and 5 days. The counter monozygotic twin fetus remained negative throughout the pregnancy according to imaging examination. A nonsense mutation in TSC2 (c.4762C>T, p.Gln1588*) was identified in both twins, but not in the mother. Family 2 was one pair of twin fetuses caused by a microdeletion of exon 30 within TSC2 inherited from their apparently asymptomatic mother with mosaic status. The larger fetus was identified as having the first cardiac rhabdomyoma from 17 weeks and 4 days of gestational age. The smaller fetus developed multiple rhabdomyomas until 25 weeks and 6 days of gestational age. Both families terminated the pregnancy. Here, we provide intrauterine examples of clinical variability among monozygotic twins suffering from TSC.

Objective:To analyze the effect of hyperbaric oxygen therapy on peritoneal dialysis（PD）patients with cognitive impairment and its impact on quality of life.Methods:A total of 120 maintenance PD patients with cognitive impairment admitted to Linyi Central Hospital from December 2019 to December 2020 were divided into observation group and control group according to the random number table method，with 60 cases in each group. Patients in both groups received conventional treatments including PD for end-stage renal disease. The control group received cognitive training，and the observation group received hyperbaric oxygen therapy on the basis of the training of the control group. The changes of cognitive function and quality of life of the patients in the two groups were compared.Results:There was no significant difference in the levels of BUN，Scr，PaO 2，PaCO 2，and pH between the two groups before and after treatment（ P>0.05）. After treatment，Hb levels in the two groups were significantly higher than those before treatment，with statistically significant differences（ P<0.05），while there was no statistically significant difference between the two groups（ P>0.05）. After treatment，the Addenbrooke’s Cognitive Examination-Revised（ACE-R）total score and sub-scale scores of patients in both groups were significantly increased than those before treatment，with statistically significant differences（ P<0.05），and those scores in the observation group were significantly higher than those in the control group，with statistically significant differences（ P<0.05）. The serum BNDF level of the observation group was significantly higher than that before treatment. The serum Hcy and CRP levels of the two groups were significantly lower than those before treatment，with statistically significant differences（ P<0.05），and those two levels of the observation group were significantly lower than those of the control group，with statistically significant differences（ P<0.05）. The indicators of quality of life in the two groups were significantly improved than those before treatment，with statistically significant differences（ P<0.05），and the indicators of the observation group were better than those of the control group，with statistically significant differences（ P<0.05）. There was no statistically significant difference in the incidence of adverse events between the two groups during treatment（ P>0.05）. Conclusion:Hyperbaric oxygen therapy can significantly improve the cognitive function and quality of life of PD patients，and it is safe and reliable，which is worthy of clinical promotion.