OBJECTIVES: To investigate the effects of early life intervention with Bifidobacterium bifidum BD-1 (B. bifidum BD-1) on hyperactivity in a female mouse model of attention deficit hyperactivity disorder (ADHD) and explore the underlying mechanisms. METHODS: Eight newborn female Wistar-Kyoto (WKY) rats and 6 spontaneous hypertensive rats (SHRs) were gavaged with saline and another 6 SHRs were gavaged with B. bifidum BD-1 (10⁹ CFU) daily for 3 weeks. Open field test of the rats was conducted at 7 weeks, and fecal samples were collected at weaning (3 weeks) and at 7 weeks for 16S rRNA sequencing. Immunofluorescent staining was used to detect dopamine transporter (DAT) and tyrosine hydroxylase (Th) levels in the striatum and activated microglia in the prefrontal cortex. Treg cells in the mesenteric lymph nodes, spleen and blood were analyzed using flow cytometry. RESULTS: The SHRs traveled a significantly greater distance in open fields test than WKY rats, and this behavior was significantly attenuated by B. bifidum BD-1 intervention. The expression of DAT and Th in the striatum was significantly lower in the SHRs than in WKY rats, while B. bifidum BD-1 treatment obviously increased Th levels in the SHRs. B. bifidum BD-1 intervention significantly deceased the number of activated microglia and increased Treg cell counts in the spleen of SHRs. The treatment also enhanced α diversity in gut microbiota of the SHRs and resulted in a decreased Firmicutes/Bacteroidota ratio, more active Muribaculaceae growth, and suppression of Clostridia_UCG-014 proliferation. CONCLUSIONS Early life intervention with B. bifidum BD-1 alleviates hyperactivity in female SHRs by modulating the gut microbiota and peripheral immune response, suppressing neuroinflammation and improving dopaminergic system function. These findings provide evidence for early prevention strategies and support the development and application of psychobiotics for ADHD.
Animals ; Female ; Rats ; Rats, Inbred WKY ; Rats, Inbred SHR ; Attention Deficit Disorder with Hyperactivity/therapy* ; Bifidobacterium bifidum ; Probiotics/therapeutic use* ; Dopamine Plasma Membrane Transport Proteins/metabolism* ; Tyrosine 3-Monooxygenase/metabolism* ; Gastrointestinal Microbiome ; Disease Models, Animal

Objective To make a preliminary investigation of the effect of the immune pathway mediated by live Lacticaseibacillus paracasei N11 15 on the development of primary hippocampal neurons cultured in vitro.Methods Live Lacticaseibacillus paracasei N1115 suspension of an appropriate concentration was used as the experimental group.Peptidoglycan(PGN)and lipopolysaccharide(LPS)were used as positive controls,and RPMI1640 medium served as the blank control.These were co-cultured with RAW264.7 cells to obtain the co-culture mediums and the total cellular RNA,and to measure the expression and secretion of cytokines.After centrifugation,the supernatants were co-cultured with primary hippocampal neurons at appropriate ratios.The co-culture mediums were collected,and the total cellular RNA was extracted to measure the expression of genes related to synaptic development in neurons.Following immunofluorescence staining of the primary hippocampal neurons,the presynaptic and presynaptic membrane-associated proteins,including synaptophysin(SYP)and the postsynaptic density protein 95(PSD95),and neuronal cell maturation markers,including microtubule-associated protein 2(MAP-2),and doublecortin(DCX)were quantitatively analyzed.Additionally,the morphological development of the neurons were measured.Results Compared with the blank control,the mRNA expression levels of interleukin(IL)-6 and tumor necrosis factor-α(TNF-α)increased by 7471％and 926％,respectively,after the RAW264.7 cells were treated with live Lacticaseibacillus paracasei N1115,while their secretion levels increased by 184.16 pg/mL and 12320.76 pg/mL,respectively,all showing statistically significant differences(P＜0.05).The activation ability of N1115 live bacteria was stronger than that of PGN but weaker than that of LPS,showing statistically significant differences(P＜0.05).Compared with the blank control,following the intervention with the supernatant from the co-culture of N1115 live bacteria and RAW264.7 cells,the viability of primary hippocampal neurons in the 10％supernatant intervention group increased by 19.25％,showing statistically significant differences(P＜0.05),and the mRNA expression of SYP and PSD95 increased by 137％and 159％,respectively,showing statistically significant differences(P＜0.05).The total neurite length(489.88 μm)of the neurons of the group intervened with the supernatant of N11 15 live bacteria was increased compared to that of the blank control group(381.51 μm),and the cell body area(2092.22 μm2),maximum neurite length(184.78 μm),total neurite length,average neurite length(108.38 μm),and branching points(4.84 s)were higher than those in the two positive control groups,showing statistically significant differences(P＜0.05).Conclusion Lacticaseibacillus paracasei N1115 can significantly activate the immune regulatory function of macrophages,thereby promoting the morphological development and synaptic function of nerve cells.

Objective To explore the value of Fast Dixon in improving the quality of thyroid turbo spin echo(TSE)T2WI images via comparing the quality of thyroid MR T2WI images based on Fast Dixon,Dixon,and BLADE sequences.Methods The prospective study included 11 healthy volunteers,who underwent neck MR scanning.The evaluation of image quality was performed via a combination of objective measures and subjective ratings.Objective measures included signal-to-noise ratio(SNR)of bilateral thyroid and muscles,and contrast-to-noise ratio(CNR).Subjective measures included overall image quality,uniformity of fat suppression,sharpness of thyroid margins and muscles surrounding the thyroid,image noise in the neck region,image background noise,and image quality of the nasopharynx.Two diagnostic physicians with over 10 years of thyroid diagnostic experience independently evaluated the images via a 5-point scale.Inter-observer agreement was analyzed via Spearman correlation coefficient.Statistical analysis was performed using SPSS 22.0 software,including normality and homogeneity of variance tests for continuous data.Kruskal-Wallis one-way ANOVA was used for statistical analysis of subjective measures,followed by post hoc pairwise comparisons.A significance level of P<0.05 was considered statistically significant.Results Eleven healthy volunteers,the SNR of bilateral thyroid and muscles was significantly higher in Fast Dixon sequence than that in Dixon and BLADE sequences.For bilateral CNR,Fast Dixon sequence was also significantly higher than that of Dixon and BLADE sequences.Fast Dixon sequence also had significant advantages in seven subjective ratings indicators(P<0.001).Conclusion The Fast Dixon sequence shows the highest image quality and important application value in the display and evaluation of thyroid lesions.

AIM: To analyze the causes of blindness and low vision in patients with visual disability in Yangpu District of Shanghai from 2019 to 2022.METHODS:Cross-sectional study. A total of 1 604 patients who participated in the evaluation of visual disability in Shanghai Yangpu District Kongjiang Hospital, from April 2019 to December 2022 were selected for the study. The grade of visual disability and the main causes of blindness and low vision were determined by trained doctors.RESULTS:A total of 804 patients with visual disabilities were identified, with 87.31% aged 60 and above. The causes of visual disability were high myopic retinopathy(30.47%), age-related macular degeneration(23.26%), glaucoma(17.04%), and diabetic retinopathy(11.07%). Glaucoma(36.96%)is the leading cause of blindness.CONCLUSION: The majority of patients with visual disability are aged 60 years and above. More attention should be paid to the elderly population. Comprehensive prevention, treatment and rehabilitation measures should be applied in different diseases based on classification, so as to early reduce the occurrence of visual disability.

Objective: He-Wei Granule (HWKL) is a modern product derived from the modified formulation of traditional Chinese medicine Banxia Xiexin Decoction (BXD), which remarkedly enhanced the anti-proliferation activity of cyclophosphamide (CTX) on HepG2 and SGC-7901 cell lines in vitro in our previous research. The aim of the study was to investigate the synergistic effects of HWKL and CTX using a transplanted H22 hepatocellular carcinoma mouse model. Methods: The CTX-toxic-reducing efficacy of HWKL was evaluated by hematology indexes, organ indexes and marrow DNA detection. To investigate the underlying mechanisms, histopathology test, immunohistochemistry test and TUNEL staining were conducted. The efficacy of HWKL on the micro-vessel density (MVD) in tumor tissue was also evaluated by measuring CD34 level. Results: High dose HWKL (6.75 g/kg) markedly attenuated CTX-induced hepatotoxicity and myelosuppression while significantly enhanced CTX anticancer efficacy in vivo. Further mechanism investigation suggested that high dose HWKL significantly increased cleaved Caspase 3 level and promoted apoptosis in tumor tissue by up-regulating Bax expression and down-regulating Bcl-2 and FasL expressions. Compared with CTX alone group, the decrease in LC-3B and Beclin 1 levels suggested that the autophagy in H22 carcinoma was significantly inhibited with addition of high dose HWKL. ELISA assay results indicated that the autophagy inhibition was achieved by decreasing p53 expression, blocking PI3K/AKT/mTOR pathway and recovering Th1/Th2 cytokine balance. In addition, CD34 and EGFR immunohistochemistry assay suggest that high dose HWKL could significantly decrease micro-vessel density (MVD) and inhibit angiogenesis in H22 carcinoma. Conclusion: It can be concluded that high-dose HWKL enhanced CTX efficacy by promoting apoptosis, inhibiting autophagy and angiogenesis in tumor tissue while significantly alleviated CTX-induced toxicity, and could be applied along with CTX in clinical treatment as a supplement agent.

Objective:To explore the relationship between cardiac discomfort symptoms, fear of disease progress and post-traumatic stress disorder (PTSD) in patients with acute myocardial infarction(AMI) after discharge, and to clarify main intervention direction of PTSD in patients with AMI.Methods:Patients with AMI who were discharged from Tangshan Gongren Hospital between 1 month and 1 year were selected from November 2019 to November 2020.The cardiac discomfort symptoms scale, fear of progress questionnaire(FoP-Q-SF) and post-traumatic stress disorder self-rating scale(PTSD-SS) were used to investigate cardiac discomfort symptoms, fear of disease progress level and post-traumatic stress disorder status.Spearman rank correlation analysis was used to analyze the relationship between cardiac discomfort symptoms, fear of disease progress and post-traumatic stress disorder by SPSS 24.0 software. The mediating effect of fear of disease progress was analyzed by AMOS 24.0 software.Results:The PTSD score was (32.78±12.38) of patients with AMI discharged from hospital for 1 month to 1 year and the incidence of PTSD was 12.3%.Spearman correlation test showed cardiac discomfort symptoms and fear of disease progress were positively correlated with PTSD( r=0.530, 0.723, both P<0.01) and cardiac discomfort symptoms was positively correlated with fear of disease progress( r=0.518, P<0.01). Mediating effect test showed that fear of disease progress was a complete mediator between cardiac discomfort symptoms and PTSD. Conclusion:Cardiac discomfort symptoms can affect PTSD through a complete mediator of fear of disease progress.

Objective: To evaluate the performance of a deep learning (DL) based mammogram calcification detection system. Methods: Screening digital mammographic examinations with standard cranio-caudal (CC) and medio-lateral oblique (MLO) views were performed in 1 431 women (5 488 mammogram images) who were enrolled between January and December in 2013. The DL system and a radiologist detect calcifications separately, and then both results are reviewed by a moreexperiencedradiologist. Sensitivities of the DL model and radiologist were compared. Different calcification morphology, distribution, BI-RADS categories, breast density and patient age were investigated by χ² tests. Results: For DL system, sensitivity of all kinds of calcifications were 96.76% (7 649/7 905). The average false positive was 1.04 per image (5 706/5 488), 3.99 per case (5 706/1 431). The false positive rate was 42.73% (5 706/13 355). There was no significant differences for DL system with different calcification distribution, BI-RADS categories, breast densities and patient ages (P>0.05). Conclusion Deep learning based mammogram calcification detection system shows high sensitivity and stability, which may help to reduce the missing rate of calcification (especially the suspicious ones).

Objective: To perform lymphocyte micronucleus analysis on radiation workers with long-term exposure to low doses ionizing radiation, Evaluate the health condition of radiation workers, and provide the evidence for strengthening surveillance of radiation workers. Methods: From January 1, 2013 to December 21, 2016, a statistical analysis and evaluation was conducted of the peripheral lymphocytes micronucleus rate in 5 901 radiation workers who had undergone medical examinations of employees at Chinese Academy of Medical Sciences Institute of Radiation Medicine. Results: The micronucleus rates in radiation workers of the on-job group were higher than the pre-job group (P<0.01) . Significant difference was found among the different sex (t=5.97) , different types (χ²=378.69) , different levels of work units (χ²=115.48) . Significant difference was found among the micronucleus rates of 672 radiation workers of the on-job group from 2013 to 2016 (χ²=92.57, P<0.01) . Conclusion The peripheral lymphocytes micronucleus rate of radiation workers were significantly higher than non-contact workers. Significant increasing trend of micronucleus rates was noted among the radiation worker with increasing exposure time. The peripheral lymphocytes micronucleus rates of interventional therapy workers were highest. The peripheral lymphocytes micronucleus rates of Private hospitals workers were highest. This phenomenon deserves attention. Protection needs to be strengthened to ensure the health of radiation workers.

Objective To observe the curative effect of Shenmai injection on patients with myocardial injury after cardiopulmonary resuscitation (CPR) and to explore its possible mechanism.Methods Sixty-two patients with cardiac arrest and respiratory arrest admitted to Qingdao Hiser Hospital from January 2010 to December 2016 were enrolled, they were randomly divided into a conventional therapy control group (30 cases) and a Shenmai treatment group (32 cases) and both groups were also treated by conventional treatment. The patients in the two groups were given basic life support of CPR and its commonly used drugs simultaneously. In Shenmai treatment group, the patients were additionally infused intravenously with 100 mL of Shenmai injection once per day. The therapeutic effect was evaluated after treatment for 7 days. On the day before treatment and 1, 3 and 7 days after treatment, the patient's blood was collected to determine the levels of myocardial injury landmarks, serum creatine kinase isoenzyme (CK-MB), cardiac troponin T (cTnT) and N-terminal B-type natriuretic peptide (NT-proBNP), and the incidences of arrhythmia of ventricular tachycardia, ventricular fibrillation (VF) and atrioventricular block were observed in the two groups; the left ventricular ejection fraction (LVEF), stroke volume (SV) and cardiac output (CO) were measured at bedside by two-dimensional echocardiography for the patients of two groups.Results In conventional therapy control group, the levels of CK-MB, cTnT showed a temporary increase after 1 day of treatment, after 3 days of treatment, CK-MB and cTnT were significantly lower than those before treatment, and reached the lowest levels after 7 days of treatment; the level of NT-proBNP after treatment showed a continuous decrease, the levels of LVEF, SV, CO were persistently increased after treatment; in Shenmai treatment group, the levels of CK-MB, NT-proBNP were decreased continuously after treatment, cTnT was firstly increase and then decrease, and reached to the lowest revels after 7 days of treatment while the levels of LVEF, SV and CO were firstly decreased and then increased gradually, and reached to the highest levels after 7 days of treatment; compared with those of conventional therapy control group, the levels of CK-MB, cTnT, NT-proBNP in Shenmai treatment group were significantly lower after 3 and 7 days of treatment [3 days of treatment: CK-MB (U/L)was 51±1 vs. 82±3, cTnT (μg/L) was 2.5±0.3 vs. 3.9±0.2, NT-proBNP (ng/L) was 5 810±103 vs. 15 965±152;7 days of treatment: CK-MB (U/L) was 27±2 vs. 56±3, cTnT (μg/L) was 1.2±0.3 vs. 2.9±0.2, NT-proBNP (ng/L) was 2 834±123 vs. 4 832±76], while LVEF, SV and CO were significantly higher than those in conventional therapy control group [3 days of treatment: LVEF was 0.47±0.03 vs. 0.45±0.02, SV (mL) was 45±5 vs. 39±4, CO (L/min) was 3.7±0.2 vs. 3.6±0.2; 7 days of treatment: LVEF was 0.59±0.02 vs. 0.51±0.03, SV (mL) was 55±4 vs. 45±2, CO (L/min) was 5.3±0.3 vs. 4.6±0.4, all P < 0.05]. After CPR, arrhythmia developed in the patients of two groups, and compared with that before treatment, there was no statistical significant difference in the incidence of arrhythmia after 1 day of treatment in Shenmai treatment group (all P > 0.05); the incidence of arrhythmia was decreased significantly after 3 and 7 days of treatment compared with those before treatment, reached to the lowest level on the 7th day of treatment, and the degree of decrease of incidence of arrhythmia in Shenmai treatment group was more obvious than those of the conventional therapy control group [ventricular tachycardia: 9.4% (3/32) vs. 20.0% (6/30), VF: 9.4% (3/32) vs. 20.0 % (6/30), atrial ventricular block: 18.8% (6/32) vs. 36.7% (11/30), all P < 0.05]. Conclusions Shenmai injection has certain protective effect on injured myocardium in patients undergoing CPR, the mechanism is possibly related to reducing the levels of CK-MB,cTnT, NT-proBNP and further improving the LVEF, SV and CO.

Objective:To explore the rule of CD8+CD25+FoxP3+ regulator T cells(Treg) in the pathogenesis of pre-eclampsia (PE) in peripheral blood.Methods:This study included 24 gestational-age-matched healthy pregnant women and 46 pregnant women diagnosed with mild PE (MPE,n=24) or severe PE (SPE,n=22) during the third trimester of gestation.An 3 ml sample of peripheral blood was drawn from each subject and anti-coagulated with heparin sodiurm The percentage of CD8 + CD25 + FoxP3 + Treg cells was detected by flow cytometry.The cytokines IL-6,IL-17A,IL-10,IL-1,IL-33 and TGF-β31 were detected using Luminex200.Peripheral blood mononuclear cells (PBMCs) were isolated frum healthy controls and treated with IL-33,the percentages of CD8+ CD25+ FoxP3 + Treg cell were measured by flow cytometric detection.Results:Compared to that of healthy pregnant controls [0.48(0.21-0.96)％],MPE patients [0.32(0.19-0.63)％] and SPE patients [0.13(0.02-0.41)％] had lower percentages of CD8+CD25+FoxP3+Treg cells (P＜0.05).Compared to HP controls,higher levels of IL-6 and IL-17A were found in MPE and SPE patients(P＜0.05) and even higher in SPE patients.The levels of IL-10,IL-1[β and IL-33 were similar in all three groups (P＞0.05).Compared to HP contruls,the levels of TGF-[β1 was significantly increased in SPE and MPE patients(P＜0.05),but no significant differences were found between these two groups (P ＞ 0.05).The percentage of CD8+ CD25+ FoxP3+ Treg cells showed a negative correlation with the serum concentrations of IL-17A (r =-0.338,P =0.338),and a positive correlation with the serum concentrations of IL-33 (r =0.548,P =0.548).After PBMCs were treated with IL-33 for five days,the percentages of CD8+CD25+FoxP3+ Treg were significantly higher than those of the contruls (P＜0.05).Conclusion:These findings suggested that the reduced CD8+ CD25 + FoxP3 + Treg cells may play a role in the pathogenesis of ore-eclamosia.