Background::Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to investigate the epigenetic mechanisms in IUGR.Methods::IUGR models were established in Sprague–Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF) 1–4 binding sites of the Igf2/H19 imprinting control region (ICR). The methylation states of CTCF1–4 binding sites were studied by pyrosequencing. Results::The IUGR models were constructed successfully. Igf2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group ( P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group ( P <0.05). In addition, knocking down Igf2 reduced the protein expression levels of AKT2-phosphorylation and PGC-1α ( P <0.05). In CTCF binding sites 1-4 of the Igf2/ H19 ICR, acetylated histones H3 (AcH3) enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. Histone H3 tri-methylated lysine 4 (H3K4me3) enrichment was significantly lower in the CTCF1–4 of newborn and 8-week-old IUGR groups ( P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group ( P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly ( P <0.05). Conclusion::The methylation status and histone modification in the Igf2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

Objective:To discuss the inhibitory effect of Schisandrin B on the proliferation of pancreatic cancer Pan02 cells,and to clarify the mechanism.Methods:CCK-8 method was used to detect the proliferation rates of the Pan02 cells after treated with different concentrations(0,0.78,1.56,3.12,6.25,12.50,and 25.00 mg·L-1)of Schisandrin B to select the optimal concentration and treatment time of Schisandrin B.The mouse pancreatic cancer Pan02 cells were divided into control group(0 mg·L-1 Schisandrin B),2.5 mg·L-1 Schisandrin B group,5.0 mg·L-1 Schisandrin B group,and 10.0 mg·L-1 Schisandrin B group.The morpholoy of Pan02 cells invarious groups was observed with light microscope;5-ethynyl-2'-deoxyuridine(EdU)staining assay was used to detect the positive expression rates of the Pan02 cells in various groups;flow cytometry was used to detect the percentages of the Pan02 cells at different cell cycles and the apoptotic rates of the cells in various groups;Western blotting method was used to detect the expression levels of cell cycle and apoptosis-related proteins in the cells in various groups.Results:The CCK-8 method results showed that after treated with Schisandrin B for 48 and 72 h,compared with 0 mg·L-1 Schisandrin B,the proliferation rates of the Pan02 cells after treated with different concentrations of Schisandrin B were decreased(P<0.01),especially at 72 h.0.25,5.0,and 10.0 mg·L-1 Schisandrin B were selected to treat the Pan02 cells,and 72 h was the treatment time.In control group,the Pan02 cells had a spindle shape,with good condition,and grew closely adhered to the wall with normal organelles and cytoplasm,in 2.5 and 5.0 mg·L-1 Schisandrin B groups,the cell volume was decreased,the intercellular adhesion was disappeared,and the cell membrane was intact but more permeable;the cytoplasm shrank and vacuolar structures appeared inside the cells,with some fragmented and floating on the surface of the solution;in 10.0 mg·L-1 Schisandrin B group,the Pan02 cells exhibited notable apoptotic bodies,indicating an apoptotic state.The EdU staining results showed that compared with control group,the rates of EdU positive cells in 2.5,5.0,and 10.0 mg·L-1 Schisandrin B groups were significantly decreased(P<0.01).The flow cytometry results showed that compared with control group,the percentages of the cells at S phase in 2.5,5.0,and 10.0 mg·L-1 Schisandrin B groups were significantly increased(P<0.01),while the percentages of the cells at G2/M phase were significantly decreased(P<0.01),and the percentages of the cells at G0/G1 phase in 5.0 amd 1.0 mg·L-1 Schisandrin groups were decreased(P<0.01);compared with control group,the apoptotic rates of the cells in 2.5,5.0,and 10.0 mg·L-1 Schisandrin B groups were significantly increased(P<0.01).The Western blotting results showed that compared with control group,the expression levels of p27,B-cell lymphoma 2(Bcl-2)associated X protein(Bax),cleaved cysteine aspartic acid protease-3(cleaved Caspase-3),and cleaved poly adenosine diphosphate(ADP)ribose polymerase(cleaved PARP)proteins in the cells in 2.5 mg·L-1 Schisandrin B group were significantly increased(P<0.05 or P<0.01),the expression levels of cyclin A2,cyclin E2,and Bcl-2 proteins in the cells in 5.0 and 10.0 mg·L-1 Schisandrin B groups were significantly decreased(P<0.05 or P<0.01),while the expression levels of p27,Bax,cleaved Caspase-3,and cleaved PARP proteins in the cells in 5.0 and 10.0 mg·L-1 Schisandrin B groups were significantly increased(P<0.01).Conclusion:Schisandrin B has an inhibitory effect on proliferation of the pancreatic cancer Pan02 cells,and its mechanism may be related to the activation of the cysteine aspartic acid protease-3(Caspase-3)pathway to induce the apoptosis and activating p27 protein to induce the arrest of cell cycle at S phase.

Objective:To investigate the clinical features of chronic spontaneous urticaria (CSU) patients with angioedema (AE) .Methods:Clinical data were collected from adult outpatients with active CSU diagnosed and treated at the First Hospital of China Medical University from January 2019 to December 2021, and analyzed retrospectively. The data included gender, age, disease duration, the presence or absence of angioedema, urticaria activity score for one day, prior treatments, previous history, family history, laboratory test results, therapeutic effect, and adverse reactions. Their treatment regimens were based on the Chinese guidelines for the diagnosis and treatment of urticaria (2018) and the American guidelines for the diagnosis and management of urticaria (2014). Statistical analysis was carried out by using Mann-Whitney U test, two-independent-sample t test, Chi-square test, corrected Chi-square test, and Fisher's exact test. Results:A total of 131 CSU patients were collected, including 78 females and 53 males. Their age at the first visit was 44.6 ± 13.3 years, and the disease duration ( M[ Q1, Q3]) was 4.0 (2.0, 10.0) months. Among these CSU patients, there were 58 with AE and 73 without AE. The disease duration was significantly longer in the CSU patients with AE (6.0 [3.0, 24.0] months) than in those without AE (3.5 [2.0, 6.0] months; Z = -2.78, P = 0.005). The urticaria activity score for one day was also significantly higher in the CSU patients with AE (5.0 [3.0, 5.3] points) than in those without AE (4.0 [3.0, 5.0] points; Z = -2.63, P = 0.008). The CSU patients with AE showed a decreased proportion of patients completely controlled by licensed-dose second-generation H1-antihistamines (sgAHs) (8.6%, 5/58) compared with those without AE (24.7%, 18/73), but an increased proportion of patients uncontrolled by licensed-dose sgAHs (91.4%, 53/58) compared with those without AE (74.0%, 54/73; Z = -2.53, P = 0.011) ; there were no significant differences in the proportions of patients completely controlled or uncontrolled by updosed sgAHs alone or combinations of 2- to 4-fold equivalent-dose sgAHs, or in the proportions of patients completely controlled or uncontrolled by combination therapy with 4-fold equivalent-dose sgAHs and non-H1-antihistamines between the CSU patients with AE and those without AE ( P > 0.05) . Conclusion:Compared with the CSU patients without AE, the CSU patients with AE had a longer disease duration, higher disease activity, a lower proportion of patients completely controlled by licensed-dose sgAHs, and a higher proportion of patients uncontrolled by licensed-dose sgAHs.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to confirm the epigenetic mechanisms in IUGR. METHODS: IUGR models were established in Sprague-Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and PPAR gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF)1-4 binding sites of the IGF2/H19 imprinting control region (ICR). The methylation states of CTCF1-4 binding sites were studied by pyrosequencing. RESULTS: The IUGR models were constructed successfully. IGF2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group (P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group (P <0.05). In addition, knocking down IGF2 reduced the protein expression levels of AKT2-P and PGC-1α (P <0.05). In CTCF binding sites 1-4 of the IGF2/H19 ICR, AcH3 enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. H3K4me3 enrichment was significantly lower in the CTCF1-4 of newborn and 8-week-old IUGR groups (P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group (P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly (P <0.05). CONCLUSION The methylation status and histone modification in the IGF2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.

Objective:To analyze the accuracy of a single-lead electrocardiogram (iECG) algorithm based on intelligent wristwatch in identifying sinus tachycardia and atrial fibrillation (AF) with rapid ventricular rate.Methods:In this non-randomized control trial, 642 patients aged ≥18 years were enrolled in the General Hospital of Chinese PLA between December 15, 2020 and May 30, 2022, with sinus tachycardia or rapid ventricular rate of AF (ranging from 111 to 145 beats/min for sinus tachycardia, from 110 to 150 beats/min for rapid ventricular rate of AF, respectively). The patients wore Huawei Watch GT2 Pro smartwatches on their left wrists, and the physiological signals detected by the smartwatches in a relaxed state were used as the measured data. The iECG algorithm developed by Huawei was used for identification. Simultaneously, 12-lead electrocardiograms (12L-ECG) were performed, and two cardiologists served as the gold standard for interpretation. Three participants who did not meet the inclusion criteria were excluded based on the detection results, and a total of 639 participants were included in the study. The accuracy of the algorithm in identifying sinus tachycardia and rapid ventricular rate AF was evaluated using metrics such as recall rate, precision rate, macro F1 score for multi-class classification.Results:Among 639 subjects, there were 469 males and 170 females. There were 389 cases of sinus tachycardia and 250 cases of rapid ventricular rate AF, with a mean age of (46.53±13.32) years. The recall rate, precision rate, and F1 value of iECG algorithm in identifying sinus tachycardia was 98.7%, 99.2% and 99.0%, respectively, while it was 98.8%, 98.0% and 98.4%, respectively for AF with rapid ventricular rate. The macro F1 of AF with rapid ventricular rate and sinus tachycardia was 98.7%. The iECG based on the intelligent wristwatch showed good consistency with the corresponding 12L-ECG waveforms.Conclusion:The intelligent wristwatch-based iECG algorithm can effectively identify sinus tachycardia and rapid ventricular rate AF, demonstrating good accuracy.

Objective:To establish a long-term mortality rate prediction model for patients aged 60 years and over with atrial fibrillation and coronary heart disease using the machine learning method, and identify the corresponding risk factors of mortality.Methods:In this retrospective cohort study, a total of 329(11 cases lost of follow-up)patients with 183 males(55.6%)and 146 females(44.4%), aged(77.8±7.3)years, and 142 patients aged 80 years or older(43.2%)were selected in our hospitals from January 2013 to March 2015.And their clinical data on atrial fibrillation and coronary heart disease were analyzed.They were divided into the death group(151 cases)and the survival group(167 cases)according to the survival outcome.In addition, 60 patients aged 60 years and over admitted to our hospitals from April to July 2015 with atrial fibrillation and coronary heart disease were selected as external data validation set.The clinical data included age, gender, body mass index, diagnosis, co-morbidity, laboratory indicators, electrocardiogram, echocardiogram, treatment data.These patients were followed up for at least 6 years, and the main adverse cardiovascular and cerebrovascular events(MACCE), including death, were recorded.Finally, the data of the enrolled patients were randomly divided into the training set and the test set according to the ratio of 9∶1, Different models were established to predict the long-term mortality of patients with atrial fibrillation and coronary heart disease by machine learning algorithm.The optimal model was established by substituting external data(60 cases)into the model for verification and comparison.The top 20 risk factors for mortality were determined by Shapley additive explanation(SHAP)algorithm.Results:A total of 329 hospitalized patients were included in this study, the overall median follow-up time was 77.0 months(95% CI: 54.0~84.0), 11 cases lost during follow-up(3.3%), and 151 cases died(45.9%). The analysis found that the areas under the ROC curve for a support vector machine(SVM)model, k-Nearest Neighbor(KNN)model, decision tree model, random forest model, ADABoost model, XGBoost model and logistic regression model were 0.76, 0.75, 0.75, 0.91, 0.86, 0.85 and 0.81, respectively.The random forest model had the highest prediction efficiency, with the accuracy of 0.789 and F1 value of 0.806, which was better than the logistic regression model[the Area Under Receiver Operating Characteristic Curve(AUC): 0.91 vs.0.81, P<0.05]. D-dimer, age, number of MACCE, left ventricular ejection fraction, serum albumin level, anemia, New York Heart Association(NYHA)grade, history of old myocardial infarction, estimated glomerular filtration rate(eGFR)and resting heart rate were important risk factors for predicting long-term mortality. Conclusions:The random forest model based on machine learning method can predict the long-term mortality of patients with atrial fibrillation and coronary heart disease aged 60 years and over, have a good identification ability.Its accuracy is higher than that of the traditional Logistic regression model.Reducing the long-term mortality and improving the long-term outcomes can be achieved by intervening on D-dimer levels, correcting hypoproteinemia and anemia, improving cardiac function and controlling resting ventricular rates.

Dental hard tissues lack the ability to self-heal. In dentin and cementum, hydroxyapatite (HA) can exist outside and/or inside collagen fibers. It is difficult to repair or regenerate HA with a highly ordered orientation in the presence of collagen fibers. At present, the biomimetic mineralization of dentin and cementum, mainly carried out by imitating its biological formation process and its physiological structure, can be divided into those originating from the fiber mineralization mechanism and those with HA as the main component. The materials used include natural materials such as demineralized dentin matrix (DDM) and calcined bovine hydroxyapatite (BHA), and synthetic materials such as polymer-induced liquid precursor (PILP) and synthetic HA. In the future, natural materials and synthetic materials should be combined for the restoration and regeneration of dentin and cementum by means of biomimetic mineralization of calcium phosphate released by remineralization solution-HA.

Objective:By establishing a rat model of experimental autoimmune thyroiditis(EAT), to investigate the effects of different iodine intake on the hippocampal morphology, monoamine neurotransmitters and ethology of the offspring of EAT rats.Methods:A total of 60 female and 20 male Lewis rats with a body weight of 50 - 60 g were selected. Female rats were divided into 4 groups (15 rats in each group) with random number table method according to their body weight: control group (NI group), thyroglobulin group (Tg group), Tg + high iodine Ⅰ group (Tg + HⅠ group), and Tg + high iodine Ⅱ group (Tg + HⅡ group), and the latter three groups were model groups. The contents of iodine in drinking water of the 4 groups were 100 μg/L, 100 μg/L, 20 mg/L and 200 mg/L, respectively. Rats in the model groups were immunized with porcine thyroglobulin (PTg) subcutaneously at multiple sites, and the NI group was injected with normal saline, once every 2 weeks, 3 times in total. The rats in each group were mated in cages according to the ratio of 3 : 1 between female and male. After experiment of the offspring, the urine samples of mother rats were collected within the previous week, urinary iodine concentration was determined by As 3+-Ce 4+ catalytic spectrophotometry; then the mother rats were killed, HE staining was used to observe the changes of thyroid histomorphology and the infiltration of inflammatory cells; serum thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) of mother rats were determined by radioimmunoassay. Brain tissues were collected from 7 days old offspring, hippocampal morphology of 7 days old offspring was observed by toluidine blue staining; the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in brain tissues of 7 days old offspring were measured by enzyme-linked immunosorbent assay (ELISA); 30 and 60 days old offspring were used for water maze-location navigation test and open field test. Results:The levels of urinary iodine increased significantly of mother rats in Tg + HⅠ and Tg + HⅡ groups than that in NI group (median, μg/L: 35 380.18, 236 847.16 vs 221.43, P < 0.05). HE staining showed that the thyroid tissue of mother rats in Tg, Tg + HⅠ and Tg + HⅡ groups had different degrees of destruction and inflammatory cells infiltration, and the degree of destruction and infiltration increased with the increase of iodine intake. Compared with NI group, the contents of TgAb and TPOAb in serum of mother rats in Tg, Tg + HⅠ and Tg + HⅡ groups were significantly increased(2.118 4 ± 0.675 1, 2.103 0 ± 0.714 1, 2.783 6 ± 1.084 3 vs 0.790 1 ± 0.101 0, P < 0.05; 1.015 8 ± 0.252 8, 1.019 5 ± 0.202 0, 0.936 6 ± 0.183 4 vs 0.692 2 ± 0.111 9, P < 0.05), and the content of TgAb in Tg + HⅡ group was significantly higher than that in Tg and Tg + HⅠ groups ( P < 0.05). Compared with NI group, the number of hippocampal neurons decreased and relative damage occurred in Tg, Tg + HⅠ and Tg + HⅡ groups of the offspring. Compared with NI group, the NE contents in brain tissues of the offspring in Tg, Tg + HⅠ and Tg + HⅡ groups decreased (pg/ml: 1 232.01 ± 253.45, 1 197.64 ± 222.46, 1 074.40 ± 366.38 vs 1 733.67 ± 158.12, P < 0.05); there were no significant differences in DA and 5-HT contents in brain tissues of offspring in each group ( P > 0.05). In the water maze-location navigation test, the latency of the Tg + HⅡ group on the 4th day of the 30 days old offspring reaching the platform was significantly longer than that of the NI and Tg groups ( P < 0.05). In the open field test, there was no significant difference in 30 and 60 days old offspring in the latency of moving the original quadrant ( P > 0.05). Conclusions:With the increase of iodine intake, the degrees of thyroid tissue destruction and inflammatory cells infiltration in EAT rats increase, and the levels of TgAb in serum increase significantly. Iodine has certain effects on the hippocampal morphology and the level of monoamine neurotransmitters in the brains of the offspring of EAT rats. The effects of different iodine-induced EAT rats on their offspring's learning, memory and spatial exploration are mainly shown in childhood.

Child atopic disease is a global public health problem.Because it can cause various mental health problems, it is getting more and more attention.In recent decades, the prevalence of child atopic diseases is dramatica-lly increasing, and children′s physical and mental health are affected to different degrees.There are several hypotheses about the potential mechanism between atopic diseases and psychological problems.Herein, the psychological and behavioral problems in children with atopic diseases and the associated mechanism will be discussed.Furthermore, it suggests that the professionals should pay more attention to the children′s psychosomatic diseases, and pay more attention to the interactive effect between atopic diseases and mental health problems.It is important for the diagnosis, prevention and intervention of children with the psychosomatic diseases.