Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Effective treatments for neuropathic pain are lacking due to our limited understanding of the mechanisms. The circRNAs are mainly enriched in the central nervous system. However, their function in various physiological and pathological conditions have yet to be determined. Here, we identified circFhit, an exon-intron circRNA expressed in GABAergic neurons, which reduced the inhibitory synaptic transmission in the spinal dorsal horn to mediate spared nerve injury-induced neuropathic pain. Moreover, we found that circFhit decreased the expression of GAD65 and induced hyperexcitation in NK1R⁺ neurons by promoting the expression of its parental gene Fhit in cis. Mechanistically, circFhit was directly bound to the intronic region of Fhit, and formed a circFhit/HNRNPK complex to promote Pol II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit intron. In summary, we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R⁺ neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.
Rats ; Animals ; Posterior Horn Cells/pathology* ; Spinal Cord Dorsal Horn/metabolism* ; Neuralgia ; Synaptic Transmission

BACKGROUND: Re-biopsy of metastasis in advanced breast cancer (ABC) has become an international convention to assist the diagnosis and evaluation of tumor heterogeneity. This study aimed to detect diagnostic diversity and inconsistencies among estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression levels between primary and metastatic lesions. METHODS: We conducted a retrospective analysis of 1670 cases of ABC patients who had undergone at least one lesion re-biopsy from January 2010 to December 2018. The pathological diagnosis of biopsies, distribution of biopsy sites, and severe puncture complications at each site were collected. In addition, the inconsistency rates and related factors of ER, PR, and HER2 expression between primary and metastatic lesions were analyzed fully considering patients' demographic profiles and disease characteristics. RESULTS: In total, 1670 cases of breast cancer (BC) patients diagnosed by pathology underwent one to four biopsies of recurrences or metastases in different sites or at different stages during the rescue treatment, producing 2019 histopathological specimens which were analyzed in the study. Pathological diagnosis showed that eight patients had benign pathological diagnoses, 11 patients had second primary malignant tumors but without recurrences of breast cancer, and 17 patients had pathologically confirmed breast cancer recurrences combined with second primary cancer. In 1173 patients who presented ER, PR, and HER2 expressions in primary and metastatic lesions, the inconsistency rates of ER, PR, and HER2 were 17.5% (205/1173), 31.3% (367/1173), and 13.9% (163/1173), respectively. The multivariate analysis showed that the age at the onset of breast cancer or adjuvant endocrine therapy was an independent factor affecting changes in PR expression level. Except one liver puncture with local hemorrhage and two lung punctures with hemopneumothorax, no other severe puncture complications occurred in 1950 non-surgical rebiopsies. CONCLUSIONS The pathological diagnosis of metastasis re-biopsy of ABC was diverse, and the ER, PR, and HER2 expression levels were inconsistent between primary and metastatic lesions. Therefore, more attention should be paid to perform biopsies of relapsed and metastatic breast cancers routinely in clinical practice.
Humans ; Female ; Breast Neoplasms/metabolism* ; Retrospective Studies ; Biomarkers, Tumor/metabolism* ; Neoplasm Recurrence, Local/pathology* ; Receptors, Progesterone/metabolism* ; Receptor, ErbB-2/metabolism* ; Receptors, Estrogen/metabolism* ; Biopsy ; Neoplasm Metastasis

Objective: To study on the difference of serum iron(Fe) levels between normal healthy people and patients with AD in order to explore the effect of serum iron level on the phenotypical division of AD patients and discuss its influence and significance in the diet nursing of AD patients. Methods: A total of 30 patients with AD in Guangzhou Huiai Hospital were selected as the "AD group" from June 2014 to August 2017, and 30 healthy people in the corresponding health center of Guangzhou Huiai Hospital were selected as "the health control group". Data of general information, serum iron and red blood cell(RBC) index were collected in these two groups. General statistical analysis and cluster analysis were made based on the data. Results: RBC in healthy control group and AD group were 4.60(4.38,5.00)×10¹²/L and (4.32±0.51)×10¹²/L. Compared with the healthy control group, RBC in the AD group was lower and the difference was statistically significant (Z=2.493, P<0.05). But, the other indexes were not significantly different (P>0.05). There was no significant difference in the in Fe level, RBC, hemoglobin and other indexes in AD patients with the different severity of dementia (P>0.05). Based on the level of Fe and RBC, the 60 cases can be divided into four types of different characteristics.The Fe of four types were (12.39±2.35) , (13.55±2.07) ,[20.70(19.55,23.15)], [19.70(17.70,22.60)] μmol/L, the RBC were (4.07±0.30), [4.83(4.62,5.12)], [4.40(4.14,4.45)], [5.00(4.80,5.34)]×10¹²/L. The HGB were (125.30±8.74), (138.08±11.1), [136.00(127.00,139.00)], (151.91±13.49)g/L.The incidence of four types of AD, Fe level, RBC and hemoglobin content were different (t/Z/χ²=0.019-6.942, P<0.05). Conclusions Based on Fe and RBC, the population can be divided into 4 types. "Low Fe and low RBC"Type, "High Fe and high RBC"Type, "Low Fe and high RBC"Type and"High Fe and low RBC"."Low Fe and low RBC"Type contains most AD patients while "High Fe and high RBC"Type contains the least. There are close in the distribution of objects between"Low Fe and high RBC" and "High Fe and low RBC". According to the characteristics of these four types, different dietary care programs may be required

Objective To evaluate the efficacy and safety of etoposide capsule on metastatic breast cancer. Methods Forty-five advanced breast cancer patients treated with oral etoposide during Feb.1,2012 and Oct.31, 2016 in our department were enrolled in our study,with their general data,median number of treatment lines, treatment effect,common adverse reaction collected. Such indexes of objective response rate,rate of clinical benefit,disease control rate,progression free survival time were anlayzed. Results All patients received median five lines of etoposide capsule therapy. The objective response rate(ORR,CR + PR)was 6.7% and the clinical benefit rate(CBR,CR+PR+SD≥6.0 months)was 26.7% and the disease control rate(DCR,CR+PR+SD) was 68.9%.The median progression free survival time(PFS)was 4.0 months(95% CI:2.3~5.6).The main toxic-ities were grade 1-2 neutropenia(37.8%),grade 3-4 neutropenia(6.7%).Conclusion Etoposide capsule could be an option with efficacy and safety for metastatic breast cancer.

BACKGROUND: Telomerase can maintain the telomere length and avoid cel replicative senescence and apoptosis in somatic cells. Its catalytic subunit cal ed telomerase reverse transcriptase has roles in mediating cellsurvival and anti-apoptotic functions. OBJECTIVE: To evaluate the effects of human telomerase reverse transcriptase on amyloid β1-40-induced human embryonic cortical neurons injury. METHODS: Human cortical neurons derived from 12-16 weeks old aborted fetuses were transfected with recombinant adenovirus vector encoding human telomerase reverse transcriptase. Expression of human telomerase reverse transcriptase was evaluated by immunocytochemical staining. Telomerase activity was measured using a PCR-based telomeric repeat amplification protocol enzyme-linked immunosorbent assay kit. Human embryonic cortical neurons were treated with 10 μmol/L ol/L amyloid β1-40 after transfected for 3 days. Cel viability, reactive oxygen species levels and glutathione contents in human embryonic cortical neurons were respectively detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate and chromatometry. RESULTS AND CONCLUSION: Expression of human telomerase reverse transcriptase reached peak at 3 days after transfection, and the telomerase activity was rebuilt; 10 μmol/L amyloid β1-40 could significantly reduce the cel viability of neurons and glutathione content (P < 0.05 and P < 0.01), and increase the reactive oxygen species levels (P < 0.05). The neurons transfected with human telomerase reverse transcriptase gene could be significantly against the toxicity of amyloid β1-40 and increase the cel viability and glutathione content (P < 0.05 and P < 0.01), and decrease the reactive oxygen species levels (P < 0.05). The results indicate that human telomerase reverse transcriptase can protect amyloid β1-40-induced human embryonic cortical neurons injury