Objective:To investigate the regulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on functional connectivity (FC) of thalamic subregions in patients with premenstrual syndrome (PMS).Methods:This study was a cross-sectional investigation. Clinical, laboratory, and imaging data were retrospectively collected from 56 PMS patients (PMS group) and 66 healthy controls (control group) recruited from various universities and hospitals in Nanning between November 2021 and June 2024. Resting-state functional MRI (fMRI) data and fMRI data during taVNS immediate stimulation (2 Hz, 25 Hz) were acquired from subjects during their late luteal phase. Using thalamic subregions (anterior thalamic nucleus, lateral nucleus, ventral nucleus, medial nucleus, central nucleus, posterior nucleus) as seeds, two-sample t-tests or paired t-tests were employed to analyze alterations in thalamic subregion FC in PMS patients and the regulatory effects of taVNS on these changes. Independent samples t-test were used to compare the differences in clinical and laboratory indicators between the PMS group and the control group. The relationship between taVNS regulation of thalamic subregion FC in PMS patients and thalamic internal functional connectivity were analyzed using mediation effect analysis. Results:Compared to the control group, patients in the PMS group showed increased scores on the Daily Record of Severity of Problems, Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale 17, and Hamilton Depression Rating Scale 14 during the late luteal phase ( P<0.05). At baseline, PMS patients exhibited higher FC between the left thalamic lateral nucleus and the left insula, and lower FC between the left medial nucleus, posterior nucleus, and ventral nucleus of the thalamus and the right middle frontal gyrus (MFG) compared to the control group (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 2 Hz taVNS immediate stimulation in PMS group, FC between the left thalamic medial nucleus, posterior nucleus, ventral nucleus and the right MFG, as well as the FC between the left thalamic ventral nucleu and the left MFG increased compared to baseline levels; meanwhile, FC between the left thalamic posterior nucleus, ventral nucleus and the left insula decreased compared to baseline levels (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 25 Hz taVNS immediate stimulation, the FC between the left thalamic ventral nucleus and the right MFG decreased compared to the baseline level (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Mediation effect analysis showed that the FC between the left thalamic posterior nucleus and the left lateral nucleus mediated part of the association between the FC of the left lateral thalamic nucleus-left insula and the FC of the left ventral thalamic nucleus-left putamen/insula; there were significant direct effects between the FC of the left lateral thalamic nucleus-the left posterior nucleus and FC of the left lateral thalamic nucleus-the left insula, as well as between the FC of the left ventral thalamic nucleus-the left MFG and FC of the left ventral thalamic nucleus-the right MFG. Conclusions:taVNS can modulate abnormal FC of the left thalamic subregions in PMS patients, restoring it toward normalization. The regulatory effects of 2 Hz stimulation are more pronounced than those of 25 Hz stimulation. This modulation primarily operates through two pathways: the left thalamic lateral nucleus-left insula-left thalamic ventral nucleus pathway and the left MFG-left thalamic ventral nucleus-right MFG.

Objective:To investigate the regulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on functional connectivity (FC) of thalamic subregions in patients with premenstrual syndrome (PMS).Methods:This study was a cross-sectional investigation. Clinical, laboratory, and imaging data were retrospectively collected from 56 PMS patients (PMS group) and 66 healthy controls (control group) recruited from various universities and hospitals in Nanning between November 2021 and June 2024. Resting-state functional MRI (fMRI) data and fMRI data during taVNS immediate stimulation (2 Hz, 25 Hz) were acquired from subjects during their late luteal phase. Using thalamic subregions (anterior thalamic nucleus, lateral nucleus, ventral nucleus, medial nucleus, central nucleus, posterior nucleus) as seeds, two-sample t-tests or paired t-tests were employed to analyze alterations in thalamic subregion FC in PMS patients and the regulatory effects of taVNS on these changes. Independent samples t-test were used to compare the differences in clinical and laboratory indicators between the PMS group and the control group. The relationship between taVNS regulation of thalamic subregion FC in PMS patients and thalamic internal functional connectivity were analyzed using mediation effect analysis. Results:Compared to the control group, patients in the PMS group showed increased scores on the Daily Record of Severity of Problems, Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale 17, and Hamilton Depression Rating Scale 14 during the late luteal phase ( P<0.05). At baseline, PMS patients exhibited higher FC between the left thalamic lateral nucleus and the left insula, and lower FC between the left medial nucleus, posterior nucleus, and ventral nucleus of the thalamus and the right middle frontal gyrus (MFG) compared to the control group (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 2 Hz taVNS immediate stimulation in PMS group, FC between the left thalamic medial nucleus, posterior nucleus, ventral nucleus and the right MFG, as well as the FC between the left thalamic ventral nucleu and the left MFG increased compared to baseline levels; meanwhile, FC between the left thalamic posterior nucleus, ventral nucleus and the left insula decreased compared to baseline levels (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 25 Hz taVNS immediate stimulation, the FC between the left thalamic ventral nucleus and the right MFG decreased compared to the baseline level (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Mediation effect analysis showed that the FC between the left thalamic posterior nucleus and the left lateral nucleus mediated part of the association between the FC of the left lateral thalamic nucleus-left insula and the FC of the left ventral thalamic nucleus-left putamen/insula; there were significant direct effects between the FC of the left lateral thalamic nucleus-the left posterior nucleus and FC of the left lateral thalamic nucleus-the left insula, as well as between the FC of the left ventral thalamic nucleus-the left MFG and FC of the left ventral thalamic nucleus-the right MFG. Conclusions:taVNS can modulate abnormal FC of the left thalamic subregions in PMS patients, restoring it toward normalization. The regulatory effects of 2 Hz stimulation are more pronounced than those of 25 Hz stimulation. This modulation primarily operates through two pathways: the left thalamic lateral nucleus-left insula-left thalamic ventral nucleus pathway and the left MFG-left thalamic ventral nucleus-right MFG.

Objective:To investigate the role of miRNA-4298/PADI4/p53 signal axis in mediating 4f-induced apoptosis of leukemia cells.Methods:The cell growth density was observed under inverted microscope and the proliferation of leukemia cells was detected by CCK-8 counting assay. The expression of PADI4 and P53 at mRNA level was detected by qRT-PCR. Cell cycle and apoptosis were measured with flow cytometry. The expression of PADI4, P53, Bcl-2, Bax, caspase-3 and caspase-9 at protein level was detected by Western blot. Differential miRNA and mRNA expression profiles was detected by next generation sequencing. Databases such as TargetScan were used to predict the potential upstream and downstream genes of PADI4. A luciferase reporter assay was used to detect the 3′UTR of PADI4 targeted by miRNA-4298. Cell transfection assay was used to detect the effect siRNA, PADI4 vector, miRNA mimics and miRNA inhibitor in interference and rescue.Results:Nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor 4f could inhibit the proliferation of THP-1, K562 and U937 cells, and induce the apoptosis of these leukemia cells. It downregulated the expression of PADI4 mainly through the binding activity of miRNA-4298 to miRNA sponges, which resulted in the proliferation inhibition and apoptosis of leukemia cells. The inhibited proliferation and apoptosis of leukemia cells by 4f were associated with the increase of P53 expression after the decrease of PADI4 expression. The PADI4-dependent upregulation of P53 led to the ratio inversion of downstream Bcl-2/Bax, which activated caspase-3 or caspase-9 to induce the apoptosis of leukemia cells.Conclusions:The apoptosis of leukemia cells induced by Nrf2 inhibitor 4f was mainly associated with the miRNA-4298/PADI4/p53 axis, suggesting that it might be a novel signaling pathway for targeted therapy.

Objective:To preliminarily evaluate the myocardium of pilots by noninvasive and radiation free cardiac MRI mapping technology, and to explore its application value in evaluating the myocardium of pilots.Methods:Case-control study was adopted in this study. Pilots and normal personnel who had cardiac MRI in Air Force Medical Center from October of 2020 to July of 2022 were selected, and they were divided into 20-40 years group and >40 years group. The differences of myocardial longitudinal relaxation time T1, transverse relaxation time T2 and T2 * values between pilots and normal personnel at different ages were analyzed and compared. Pilots were divided into groups according to flying hours and aircraft types, and the differences of myocardial T1, T2 and T2 * values among pilots in different flying hours and aircraft types were analyzed and compared. Results:The average myocardial T1 value of pilots [(1 011.18±24.70) ms] was lower than that of normal personnel [(1 025.07±25.74) ms], and the difference was significant ( t=2.10, P=0.040). The myocardial T1 value of pilots >40 years old [(1 006.04±29.15)ms] was lower than that of normal personnel [(1 029.68±20.24) ms], and the difference was significant ( t=2.30, P=0.032). The myocardial T1 value of fighter pilots [(999.04±17.39)ms] was lower than that of the bomber, transporter, helicopter pilots [(1 023.33±25.53) ms], and the difference was significant ( t=2.73, P=0.012). There was no significant difference in myocardial T1, T2 and T2 * values between pilots and nornal personnel aged 20-40 years old; there was no significant difference in T2 and T2 * values between pilots and normal personnel in the age group of >40 years old (all P>0.05). There was also no significant difference in myocardial T1, T2 and T2 * values among the pilots in different flying hours (all P>0.05). Conclusions:The level of cardiomyocyte hypertrophy or myocardial fibrosis in fighter pilots might be lower than that in other aircraft types pilots. Cardiac MRI mapping has potential value in evaluating the myocardium of pilots.

Objective:To preliminarily evaluate the myocardium of pilots by noninvasive and radiation free cardiac MRI mapping technology, and to explore its application value in evaluating the myocardium of pilots.Methods:Case-control study was adopted in this study. Pilots and normal personnel who had cardiac MRI in Air Force Medical Center from October of 2020 to July of 2022 were selected, and they were divided into 20-40 years group and >40 years group. The differences of myocardial longitudinal relaxation time T1, transverse relaxation time T2 and T2 * values between pilots and normal personnel at different ages were analyzed and compared. Pilots were divided into groups according to flying hours and aircraft types, and the differences of myocardial T1, T2 and T2 * values among pilots in different flying hours and aircraft types were analyzed and compared. Results:The average myocardial T1 value of pilots [(1 011.18±24.70) ms] was lower than that of normal personnel [(1 025.07±25.74) ms], and the difference was significant ( t=2.10, P=0.040). The myocardial T1 value of pilots >40 years old [(1 006.04±29.15)ms] was lower than that of normal personnel [(1 029.68±20.24) ms], and the difference was significant ( t=2.30, P=0.032). The myocardial T1 value of fighter pilots [(999.04±17.39)ms] was lower than that of the bomber, transporter, helicopter pilots [(1 023.33±25.53) ms], and the difference was significant ( t=2.73, P=0.012). There was no significant difference in myocardial T1, T2 and T2 * values between pilots and nornal personnel aged 20-40 years old; there was no significant difference in T2 and T2 * values between pilots and normal personnel in the age group of >40 years old (all P>0.05). There was also no significant difference in myocardial T1, T2 and T2 * values among the pilots in different flying hours (all P>0.05). Conclusions:The level of cardiomyocyte hypertrophy or myocardial fibrosis in fighter pilots might be lower than that in other aircraft types pilots. Cardiac MRI mapping has potential value in evaluating the myocardium of pilots.

Mutations of the X-linked methyl-CpG-binding protein 2 (MECP2) gene in humans are responsible for most cases of Rett syndrome (RTT), an X-linked progressive neurological disorder. While genome-wide screens in clinical trials have revealed several putative RTT-associated mutations in MECP2, their causal relevance regarding the functional regulation of MeCP2 at the etiologic sites at the protein level requires more evidence. In this study, we demonstrated that MeCP2 was dynamically modified by O-linked-β-N-acetylglucosamine (O-GlcNAc) at threonine 203 (T203), an etiologic site in RTT patients. Disruption of the O-GlcNAcylation of MeCP2 specifically at T203 impaired dendrite development and spine maturation in cultured hippocampal neurons, and disrupted neuronal migration, dendritic spine morphogenesis, and caused dysfunction of synaptic transmission in the developing and juvenile mouse cerebral cortex. Mechanistically, genetic disruption of O-GlcNAcylation at T203 on MeCP2 decreased the neuronal activity-induced induction of Bdnf transcription. Our study highlights the critical role of MeCP2 T203 O-GlcNAcylation in neural development and synaptic transmission potentially via brain-derived neurotrophic factor.
Animals ; Humans ; Methyl-CpG-Binding Protein 2/metabolism* ; Mice ; Neurodevelopmental Disorders/genetics* ; Rett Syndrome/genetics* ; Synaptic Transmission ; Threonine

Objective: To investigate the difference in intestinal microbiome between children with atopic dermatitis (AD) and healthy children. Methods: Totally, 35 children with AD were enrolled from the Department of Dermatology, Jiading Hospital of Traditional Chinese Medicine from April 2015 to April 2017, and 27 healthy children served as control group. Total DNA was extracted from the feces of the subjects, and the V3-V4 region of the 16S rRNA gene of the bacteria was amplified by PCR. High-throughput sequencing was performed using the Illumina Miseq sequencing platform to analyze the diversity of bacterial flora. The top 15 abundant bacteria were determined at phylum, genus, and species levels, and compared between the two groups. Statistical analysis was carried out using Wilcoxon rank sum test. Results: The intestinal microbiome in the two groups mainly consisted of Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria. At the phylum level, the abundance of Bacteroidetes and Fusobacteria was significantly lower in the AD group (29.16% ± 19.96%, 0.06% ± 0.17%, respectively) than in the healthy control group (39.06% ± 15.98%, 0.50% ± 1.71%, respectively, P = 0.042, 0.041) . At the genus level, the abundance of Bacteroides was significantly lower in the AD group (23.77% ± 18.08%) than in the healthy control group (33.1% ± 15.75%, P = 0.029) . There was no significant difference in the distribution of the top 15 abundant species between the two groups (all P > 0.05) . Conclusion There are some differences in the composition of intestinal microbiome and relative abundance of bacteria between children with AD and healthy children.

Objective:To study the relationship between the expression of filamin A (FLNa) and clinical pathological features in invasive breast carcinoma. Methods:The expression of FLNa was measured by immunohistochemistry and flow cytometry in 46 cases of invasive breast carcinoma. Results:The expression level of FLNa was increased in poorly differentiated invasive breast carcinoma. There were significant differences between well-moderately differentiated and poorly differentiated groups (P<0.05). The expression level of FLNa in invasive breast carcinoma with lymph node metastasis was higher than that in non-metastasis group (P<0.05). Conclusion:The level of FLNa expression correlated with invasion and metastasis of invasive breast carcinoma. FLNa can be used as an assistant marker for prediction of breast carcinoma prognosis and has the potential to be a new target for cilinical therapy.

BACKGROUNDTo investigate the clinical characteristics and diagnosis of lung cancer with paraneoplastic syndrome as initial symptom.

METHODSThe clinical data of 168 cases of lung cancer with paraneoplastic syndrome as initial symptom were analysed from Jan. 1990, to Nov. 2002, in the hospital.

RESULTS(1) Among the patients with lung cancer in the hospital, 11.8% (168/1 426) had paraneoplastic syndrome as initial symptom. The ratio of male to female was 4.25:1. There were 138 cases aged above 45 (82.1%) and 116 with smoking history (69.0%). (2)There were 62 cases of small cell lung cancer (36.9%) and 102 non small cell lung cancer (60.7%) and 4 carcinoid (2.4%). Thirty-three cases (37.5%) were central type and 82 (48.8%) peripheral type and 23 (13.7%) diffuse type. (3) The patients with paraneoplastic syndrome included: 48 cases of osteoarthopathy (28.6%), 27 cachexia (16.1%), 23 cancerous fever (13.7%), 14 myasthenia (8.3%), 12 vegetative nerve hyperfunction (7.1%), 11 cerebellar cortex degeneration (6.5%), 9 acanthosis nigricans (5.4%), 8 cutaneous pigmentation (4.8%), 7 dermatomyositis (4.2%), 5 encephalopathy (3.0%), and 4 gynecomastia (2.4%). (4)The misdiagnosis rate of the first consultation was 44.6% (75/168). (5)Initial chest X-ray positive rate was 61.9% (104/168); initial CT positive rate was 78.6% (132/168). (6)One hundred and thirty-two cases accepted the treatment of lung cancer: 32 cases accepted pure operation, 8 cases accepted pure chemotherapy, 35 cases accepted operation and chemotherapy, 39 cases accepted chemotherapy and radiotherapy, 18 cases accepted operation and chemotherapy and radiotherapy. Totally 8 cases were dead and 17 cases had abandoned treatment. One hundred and seven cases had improvement after complex treatment of lung cancer, including 83 cases with improvement or disappearance of paraneoplastic syndrome, 18 cases with no change, and 6 cases exacerbated.

CONCLUSIONSThe lung cancer with paraneoplastic syndrome as initial symptom is difficult to diagnose because of its latent onset. The knowledge of paraneoplastic syndrome should be improved, chst X-ray or CT examination should be done for the high risk group of lung cancer with paraneoplastic syndrome, and these strategies could decrease misdiagnosis rate and increase diagnosis rate of lung cancer in early stage.