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BACKGROUND: Lactylation, a newly discovered PTM involving lactic acid, is linked to solid tumor proliferation and metastasis. Lymphoma patients exhibit high lactic acid levels, yet lactylation's role in lymphoma is underexplored. This study aimed to identify lactylation-related genes in lymphoma using tumor databases and assess their predictive value in patient prognosis through cell experiments and clinical specimens. METHODS: Using TCGA and GEO datasets, we analyzed the expression levels of lactylation-related genes in diffuse large B-cell lymphoma patients. We also evaluated the prognostic significance of lactylation gene risk scores, exploring their impact on drug sensitivity and tumor immune function. Key lactylation-affecting genes were identified and functionally validated through cell experiments and mouse in vivo experiments. Additionally, the relationship between lactylation and lymphoma prognosis was examined in clinical specimens. RESULTS: We identified 70 genes linked to diffuse large B-cell lymphoma prognosis from the lactylation-related gene set. Using clinical data and a COX regression algorithm, we developed an optimized lactylation Riskscore model. This model significantly correlated with prognosis and showed differences in immune cell infiltration, particularly macrophages. High-risk patients showed resistance to chemotherapy drugs but responded well to immunotherapy. HNRNPH1, a lactylation-related gene, influenced patient prognosis, apoptosis, cell cycle distribution in lymphoma cells, and tumor volume in mice. In lymphoma specimens, lactylation levels correlated with Bcl-2, C-myc, and P53 levels. CONCLUSIONS: Lactylation impacts diffuse large B-cell lymphoma prognosis, tumor immune function, and drug resistance. Our lactylation-based Riskscore model aids in patient stratification and treatment selection. HNRNPH1 regulates lactylation, thereby affecting patient prognosis.
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OBJECTIVE: To investigate the inhibitory effect of Celastrus orbiculatus extracts (COE) on the proliferation of lymphoma cells and the immune regulation ability on inflammation and thrombophilia in vivo. METHODS: The 38B9 lymphoma cells were treated with COE (160 µ g/mL) and CTX (25 µ mol/L). The apoptosis rate and cell cycle of each group were detected by flow cytometry. The secretion of inflammatory factors, including interleukin (IL)-6, IL-10, and tumor necrosis factor α (TNF-α), in cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). In vivo, BALB/c mice were subcutaneously injected with 38B9 lymphoma cells to establish lymphoma model. COE (3 mg·kg-1·d-1) and CTX (40 mg·kg-1·d-1) were administered to the model mice, respectively. The expression of plasma inflammatory factors (IL-6, IL-10 and TNF-α) and thrombus indexes, including D-dimer (D-D), von Willebrand factor (vWF) and tissue factor (TF), were detected by ELISA before tumor bearing (1 d), after tumor formation (14 d) and after intervention (21 d). PicoGreen dsDNA was used to detect the level of serum neutrophil extracellular traps (NETs). Flow cytometry was used to detect the expression of platelet activation marker calcium-dependent lectin-like receptor 2 (CLEC-2). The tumor growth and survival of mice were recorded. RESULTS: The 38B9 lymphoma cells were apoptotic after the intervention of COE and CTX. The ratio of G2-M phase cells decreased in COE intervented cells compared with the control cells (P<0.05), and S phase cells decreased in CTX intervented cells (P<0.05). Also, the secretion level of IL-6 was significantly reduced after COE or CTX intervention (P<0.05), and IL-10 was significantly increased (P<0.05). Furthermore, the tumor mass was reduced, and the median survival time was longer in COE and CTX intervented tumor-bearing mice than in non-intervented mice. The significantly lower levels of TNF-α, IL-6, NETs, TF, DD and CLEC-2, as well as higher IL-10 were observed in COE and CTX treatment mice in comparision with the control mice (P<0.05). CONCLUSION: COE has a mild and stable anti-tumor effect, which can reduce the secretion of inflammatory factors by lymphoma cells and regulate thrombophilic state caused by tumor inflammatory microenvironment.
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Given the complexity and heterogeneity of Alzheimer's disease (AD) pathology, targeted monotherapy drugs may not be effective. Therefore, synergistic combination therapy of curcumin and Mito Q was proposed and evaluated in a triple-transgenic AD model mice (3 × Tg-AD mice). The cognitive ability was assessed using behavioral tests and typical pathological changes were observed through Western blotting and histological analysis. The results demonstrated a significant enhancement in cognitive ability along with the mitigation of typical AD pathological features such as Aß aggregation, tau phosphorylation, and synaptic damage. Notably, the combination therapy demonstrated superior efficacy over individual drugs alone. These findings provide valuable insights for optimizing the development of AD drugs.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Disfunção Cognitiva , Curcumina , Modelos Animais de Doenças , Sinergismo Farmacológico , Camundongos Transgênicos , Proteínas tau , Curcumina/farmacologia , Curcumina/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Animais , Disfunção Cognitiva/tratamento farmacológico , Proteínas tau/metabolismo , Peptídeos beta-Amiloides/metabolismo , Camundongos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/metabolismo , Fosforilação/efeitos dos fármacos , HumanosRESUMO
BACKGROUND: The objective of this research was to elucidate the association between the length of infertility and the outcomes of intrauterine insemination (IUI) in women of varying ages - a topic that has been the subject of investigation for numerous years, yet lacks a definitive consensus. METHODS: A retrospective cohort investigation involving 5268 IUI cycles was undertaken at the Reproductive Medicine Center of Nanjing Drum Tower Hospital from 2016 to 2022. Utilizing the smooth fitting curve along with threshold and saturation effect analysis, the correlation between infertility duration and IUI clinical pregnancy rates was discerned. Moreover, patients were bifurcated into two cohorts based on their respective infertility durations. A secondary examination was also performed employing propensity-score matching to mitigate the impact of confounding variables. Subsequent threshold and saturation effect analysis was carried out across various subgroups, segmented on the basis of age differentiation. RESULTS: When the duration of infertility was more than 5 years, the clinical pregnancy rate decreased with the increase of infertility duration (aOR: 0.894, 95%CI: 0.817-0.991, p = 0.043). The multivariate regression analysis suggested that longer duration of infertility (≥ 5 years) was significantly correlated with the lower clinical pregnancy rate (aOR: 0.782, 95% CI: 0.643-0.950, p = 0.01). After the propensity-score matching, the clinical pregnancy rate of women with longer infertility duration were also higher. When the duration of infertility was more than 5 years, the clinical pregnancy rate of women younger than 35 years old decreased with the increase of infertility duration (aOR: 0.906, 95%CI: 0.800-0.998, p = 0.043). CONCLUSIONS: The clinical pregnancy rate and live birth rate of IUI in young women (< 35 years old) who have been infertile for more than 5 years significantly decrease with the prolongation of infertility time. Therefore, for young women who have been infertile for more than 5 years, IUI may not be the best choice.
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Infertilidade , Gravidez , Humanos , Feminino , Adulto , Estudos Retrospectivos , Infertilidade/terapia , Fertilização in vitro , Taxa de Gravidez , InseminaçãoRESUMO
Background: Previous studies suggested higher serum progesterone (P) levels were strongly associated with a lower clinical pregnancy rate (CPR) for in vitro fertilization-embryo transfer (IVF-ET). However, the effect of increased serum P levels on the day of human chorionic gonadotropin (hCG) administration on clinical outcomes in short-acting gonadotropin-releasing hormone agonist (GnRHa) downregulated IVF-ET cycles remains unclear. Methods: We conducted a retrospective cohort study from January 2017 to December 2021, which included a total of 1664 patients receiving their first short-acting GnRHa IVF-ET cycles at our reproductive medicine centre of Nanjing Drum Tower Hospital. The smooth curve fitting and interaction analysis were employed to analyse the association between the CPR and the serum P levels with different embryo types (cleavage-stage embryo or blastocyst). In addition, total cycles were grouped according to different P levels on the trigger day of hCG administration for further analysis. Results: The CPR of patients with increased serum P level (higher than 1.5 ng/mL) on the hCG day did not decrease. A smoothing curve fitting showed that the CPR did not change obviously with the increase in serum P levels. Subgroup analysis of different types of embryos transferred showed that no correlation was observed between the CPR and serum P levels on the day of hCG administration in cleavage-stage embryo transfer cycles. However, the CPR of patients receiving blastocyst transfer showed a downward trend with the increase in serum P levels. At the same time, an interaction analysis also confirmed that the CPR of blastocyst transfer was more likely to be affected by elevated serum P levels on the hCG day. Conclusion: In the luteal phase short-acting GnRHa downregulated IVF-ET cycles, the elevated serum P levels on the hCG day did not affect the CPR of cleavage-stage embryo transfer but reduced the CPR of blastocyst transfer.
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Based on Au nano-cone array (Au-NCA) and a three-segment hybridization strategy, a novel SERS biosensor is proposed for the ultrasensitive detection of the microRNA miR-21. The uniform, stable, and reproducible Au-NCA was prepared by the single-layer colloidal ball template method. Subsequently, the target was hybridized with sequence 2. The resulting target-sequence 2 complex was then hybridized with sequence 1 anchored on Au-NCA. Thus, a three-segment sequence complex was formed. SERS measurements can be performed without the need for complex purification and amplification steps. Due to the ability of miR-21 to perform specific complementary hybridization with two sequences, SERS biosensors have superior specificity for miR-21 without interference from other miRNAs. Under the optimal conditions, the SERS biosensor was applied and the limit of detection (LOD) was as low as 3.02 aM. This method has been successfully used to the detection of miR-21 in the serum of lymphoma patients and healthy volunteers. The results are consistent with the traditional test methods. Therefore, this novel SERS biosensor shows excellent clinical translational potential in the detection of lymphoma.
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Nanopartículas Metálicas , MicroRNAs , Humanos , Análise Espectral Raman/métodos , Ouro , Hibridização de Ácido NucleicoRESUMO
Parkinson's disease is a common neurodegenerative disease characterized by intracellular aggregation of misfolded α-synuclein as a major pathological hallmark. Exosomes are cell-derived lipid bilayer membrane vesicles with various components, including proteins, RNA, and lipids, that mediate intercellular communication. Currently, exosomes are found to be responsible for transporting misfolded proteins from unhealthy neurons to nearby cells, spreading the disease from cell to cell. Such exosomes can also be found in the cerebrospinal fluid and blood. Thus, exosomes may serve as a potential tool to detect the pathology of Parkinson's disease for clinical diagnosis. In this article, the role and challenges of exosomes in the diagnosis of Parkinson's disease are outlined.
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Cognitive impairment is typically reflected in the time and frequency variations of electroencephalography (EEG). Integrating time-domain and frequency-domain analysis methods is essential to better understand and assess cognitive ability. Timely identification of cognitive levels in early Parkinson's disease (ePD) patients can help mitigate the risk of future dementia. For the investigation of the brain activity and states related to cognitive levels, this study recruited forty ePD patients for EEG microstate analysis, including 13 with mild cognitive impairment (MCI) and 27 without MCI (control group). To determine the specific frequency band on which the microstate analysis relies, a deep learning framework was employed to discern the frequency dependence of the cognitive level in ePD patients. The input to the convolutional neural network consisted of the power spectral density of multi-channel multi-point EEG signals. The visualization technique of gradient-weighted class activation mapping was utilized to extract the optimal frequency band for identifying MCI samples. Within this frequency band, microstate analysis was conducted and correlated with the Montreal Cognitive Assessment (MoCA) Scale. The deep neural network revealed significant differences in the 1-11.5Hz spectrum of the ePD-MCI group compared to the control group. In this characteristic frequency band, ePD-MCI patients exhibited a pattern of global microstate disorder. The coverage rate and occurrence frequency of microstate A and D increased significantly and were both negatively correlated with the MoCA scale. Meanwhile, the coverage, frequency and duration of microstate C decreased significantly and were positively correlated with the MoCA scale. Our work unveils abnormal microstate characteristics in ePD-MCI based on time-frequency fusion, enhancing our understanding of cognitively related brain dynamics and providing electrophysiological markers for ePD-MCI recognition.
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Disfunção Cognitiva , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Disfunção Cognitiva/diagnóstico , Encéfalo/fisiologia , Eletroencefalografia/métodos , CogniçãoRESUMO
Hemophagocytic lymphohistiocytosis (HLH) is a fatal clinical syndrome. The most common cause of secondary HLH is Epstein-Barr virus (EBV) infection. EBV-HLH is a common clinical disease with high mortality, easy relapse, and poor prognosis. Therefore, treating EBV-HLH with T and B lymphocyte involvement is challenging, and selecting an appropriate treatment regimen is critical. Moreover, research on how to evaluate the recurrence index after remission is scarce. In this study, we reported a case of EBV-HLH successfully treated with programmed cell death protein-1 (PD-1) inhibitor in combination with rituximab. The regimen had a good curative effect, and we successfully detected the trend of early recurrence. Our findings indicated that PD-1 inhibitor in combination with rituximab may help to treat EBV-HLH and maintain EBV-infected T and B whole-line lymphocytes.
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Infecções por Vírus Epstein-Barr , Linfo-Histiocitose Hemofagocítica , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/complicações , Herpesvirus Humano 4 , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Rituximab/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos B , Doença CrônicaRESUMO
Research question: Hormone replacement therapy (HRT) is one of the most used endometrial preparation protocols for frozen embryo transfer (FET) due to the convenience of its administration and stability of pregnancy outcomes. There are several HRT cycles accompanied by the development of dominant follicles. However, the relationship between dominant follicle development and clinical outcomes in HRT-FET cycles remains unclear. Design: We carried out a retrospective cohort study of 13251 cycles at our reproductive medicine center from 2012 to 2019. Total cycles were divided into two groups according to whether there was dominant follicular development. In addition, we conducted a secondary analysis that used propensity-score matching to reduce confounding variables. A univariate and multivariable logistic regression model was further employed to analyze the effect of dominant follicle development in HRT cycles on clinical pregnancy outcomes. Results: There was no significant correlation between dominant follicle development in HRT-FET cycles and the clinical pregnancy rate (adjusted OR = 1.162, 95% CI: 0.737-1.832, P = 0.52). In addition, there was a positive correlation between the basic follicle-stimulating hormone (FSH) level and the development of dominant follicles, while there was a negative correlation between antral follicle count (AFC), menstrual cycle length and the development of dominant follicles in HRT cycles. Conclusions: The development of dominant follicles in HRT-FET cycles does not affect the clinical pregnancy rate, early miscarriage rate and live birth rate. Therefore, it is not necessary to immediately cancel the FET cycle immediately when dominant follicle development is monitored in the HRT-FET cycle.
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Aborto Espontâneo , Feminino , Gravidez , Humanos , Estudos Retrospectivos , Coeficiente de Natalidade , Transferência Embrionária , Terapia de Reposição HormonalRESUMO
INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a clinically useful therapy for depression. However, the effects of rTMS on the metabolism of fatty acids (FAs) and the composition of gut microbiota in depression are not well established. METHODS: Mice received rTMS (15 Hz, 1.26 T) for seven consecutive days after exposure to chronic unpredictable mild stress (CUMS). The subsequent depressive-like behaviors, the composition of gut microbiota of stool samples, as well as medium- and long-chain fatty acids (MLCFAs) in the plasma, prefrontal cortex (PFC), and hippocampus (HPC) were evaluated. RESULTS: CUMS induced remarkable changes in gut microbiotas and fatty acids, specifically in community diversity of gut microbiotas and PUFAs in the brain. 15 Hz rTMS treatment alleviates depressive-like behaviors and partially normalized CUMS induced alterations of microbiotas and MLCFAs, especially the abundance of Cyanobacteria, Actinobacteriota, and levels of polyunsaturated fatty acids (PUFAs) in the hippocampus and PFC. CONCLUSION: These findings revealed that the modulation of gut microbiotas and PUFAs metabolism might partly contribute to the antidepressant effect of rTMS.
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Microbioma Gastrointestinal , Estimulação Magnética Transcraniana , Camundongos , Animais , Depressão/terapia , Depressão/metabolismo , Encéfalo/metabolismo , Ácidos Graxos/metabolismo , Ácidos Graxos/farmacologia , Hipocampo/metabolismo , Estresse Psicológico/terapia , Estresse Psicológico/metabolismoRESUMO
The pathogenesis of Alzheimer's disease (AD) is highly complex and multifactorial. Compared with Aß, the pathological changes associated with tau are more related to the clinical symptoms and more indicative of the severity of AD. Studies have shown that the direct interaction between tau and Zn2+ plays an important role in tau toxicity, however, the mechanism by which Zn2+ contributes to tau-induced neurotoxicity is not fully understood. Our previous studies have found that Zn2+ bound to the third repeat unit of the microtubule-binding domain of tau (R3) with moderate affinity and induced R3 to form oligomers, thus increased the toxicity of R3 to nerve cells. Here, we demonstrated that Zn2+ binding to R3 (Zn2++R3) significantly reduced cognitive ability and increased blood lipid and glucose levels of C57BL/6J mice. In addition, Zn2++R3, not Zn2+ or R3 alone, markedly enhanced the endogenous Aß and tau pathology and damaged the neurons of C57BL/6J mice. The study suggests that the main reason for the toxicity of Zn2+ may be the formation of Zn2+ and tau complex. Thus, preventing the combination of Zn2+ and tau may be a potential strategy for AD treatment. Furthermore, as the C57BL/6J mice injected with Zn2++R3 complex showed behavioral deficits, deposition of Aß plaques and tau tangles, and the death of neurons within 45 days. Thus, they can be considered as a fast sporadic AD or other tauopathies mouse model.
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Doença de Alzheimer , Tauopatias , Camundongos , Animais , Doença de Alzheimer/metabolismo , Zinco/metabolismo , Proteínas tau/química , Camundongos Endogâmicos C57BL , Tauopatias/patologia , Modelos Animais de Doenças , Peptídeos beta-Amiloides/metabolismoRESUMO
Research question: To investigate the effects of two protocols (hormone replacement therapy (HRT) alone or in combination with tamoxifen) on the endometrium and pregnancy outcome of patients with thin endometrium in frozen-thawed embryo transfer (FET) cycles. Design: A total of 465 infertile patients with thin endometrium who underwent FET between January 2020 to June 2021 at the Drum Tower Hospital affiliated with Nanjing University Medical School were retrospectively analyzed. A total of 187 patients were given tamoxifen in addition to HRT (TMXF-HRT group), whereas 278 patients were given only HRT (HRT group). Clinical data were compared between the two groups, including general characteristics, endometrial thickness, and clinical pregnancy outcomes. Results: There were no significant differences in baseline characteristics of all enrolled patients between two groups. Serum progesterone (P) was higher in HRT group than in the TMXF-HRT group (0.28 ± 0.53 ng/mL vs. 0.15 ± 0.25 ng/mL, P = 0.002). There was a significant increase in endometrial thickness in the TMXF-HRT group compared with the HRT group (OR: 1.54, 95% CI: 1.32-1.75, P < 0.001). There were no significant differences in the clinical pregnancy rate, embryo implantation rate, early miscarriage rate, or live birth rate between these two groups. Conclusion: Although tamoxifen when used in combination with hormone replacement therapy can significantly increase endometrial thickness, it may not have a role in improving the pregnancy outcomes of patients with thin endometrium undergoing FET cycles.
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Endométrio , Tamoxifeno , Gravidez , Humanos , Feminino , Estudos Retrospectivos , Tamoxifeno/uso terapêutico , Tamoxifeno/farmacologia , Transferência Embrionária/métodos , Terapia de Reposição HormonalRESUMO
BACKGROUND: Neural oscillations play a role in the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS). However, the effects of high-frequency rTMS on the neural oscillations of the medial prefrontal cortex (mPFC) and hippocampus (HPC) and its molecular mechanism have not been fully clarified. METHODS: The depressive-like behaviours, local field potentials (LFPs) of the ventral HPC (vHPC)-mPFC, and alternations of endocannabinoid system (ECS) in the HPC and mPFC were observed after rTMS treatment. Meanwhile, depressive-like behaviours and LFPs were also observed after cannabinoid type-1 receptor (CB1R) antagonist AM281 or monoacylglycerol lipase inhibitor JZL184 injection. Moreover, the antidepressant effect of rTMS was further assessed in glutamatergic-CB1R and gamma-amino butyric acid (GABA)-ergic -CB1R knockout mice. RESULTS: Alternations of endocannabinoids and energy value and synchronisation of mPFC-vHPC, especially the decrease of theta oscillation induced by CUMS, were alleviated by rTMS. JZL184 has similar effects to rTMS and AM281 blocked the effects of rTMS. GABAergic-CB1R deletion inhibited CUMS-induced depressive-like behaviours whereas Glutaminergic-CB1R deletion dampened the antidepressant effects of rTMS. LIMITATIONS: The immediate effect of rTMS on field-potential regulation was not observed. Moreover, the role of region-specific regulation of the ECS in the antidepressant effect of rTMS was unclear and the effects of cell-specific CB1R knockout on neuronal oscillations of the mPFC and vHPC should be further investigated. CONCLUSION: Endocannabinoid system mediated the antidepressant effects and was involved in the regulation of LFP in the vHPC-mPFC of high-frequency rTMS.
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Endocanabinoides , Estimulação Magnética Transcraniana , Camundongos , Animais , Endocanabinoides/farmacologia , Córtex Pré-Frontal/fisiologia , Camundongos Knockout , HipocampoRESUMO
OBJECTIVE: To investigate the in vivo intervention and relative mechanism of Genistein (GEN) on tumor-associated inflammatory and tumor thrombophilia in lymphoma-bearing mice. METHODS: Forty female Balb/c mice aged 5-6 weeks were injected with murine-derived Pro B-cell lymphoma cell line 38B9 to establish a lymphoma mouse model, which was randomly divided into control group, tumor-bearing group, GEN drug intervention group and cyclophosphamide (CTXï¼drug intervention group. Histopathologic was used to evaluate the tumorigenesis. Tumor formation was observed, and tumor tissues were collected of HE and immunohistochemical staining. ELISA and flow cytometry were used to detect the expression of inflammatory factors and the changes of thrombus indices in plasma after intervention of GEN and Cyclophosphamide (CTX) respectively. Immunohistochemistry method was used to detect the expression of CD19 in tomor tissues of tummor bearing mice. RESULTS: After 14 days of tumor bearing, the mice were tumorigenic. The lymphoma cells were diffusely distributed in the tumor tissue and the expression of CD19 in the tumor tissue was positive. The inflammatory factors such as IL-6, NETs and CLEC-2, and thrombotic indices such as TF, FIB and D-D in lymphoma-bearing mice were significantly higher than those before tumor-injection and lower than those after drug-intervention (all P<0.05). The levels of CLEC-2 and D-D in GEN group were significantly lower than those in CTX group (P<0.05). CONCLUSION: Tumor-associated inflammation and thrombophilia exist in lymphoma-bearing mice. GEN shows better anti-inflammatory and anti-thrombotic effects compared with CTX by interfering with tumor inflammatory factors.
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Linfoma , Trombofilia , Camundongos , Feminino , Animais , Genisteína , Ciclofosfamida , Inflamação , Lectinas Tipo CRESUMO
Background and Objectives: Disturbance of tryptophan (Trp) and fatty acid (FA) metabolism plays a role in the pathogenesis of psychiatric disorders. However, quantitative analysis and comparison of plasma Trp metabolites and medium- and long-chain fatty acids (MCFAs and LCFAs) in adult patients with major depressive disorder (MDD) and schizophrenia (SCH) are limited. Materials and Methods: Clinical symptoms were assessed and the level of Trp metabolites and MCFAs and LCFAs for plasma samples from patients with MDD (n = 24) or SCH (n = 22) and healthy controls (HC, n = 23) were obtained and analyzed. Results: We observed changes in Trp metabolites and MCFAs and LCFAs with MDD and SCH and found that Trp and its metabolites, such as N-formyl-kynurenine (NKY), 5-hydroxyindole-3-acetic acid (5-HIAA), and indole, as well as omega-3 polyunsaturated fatty acids (N3) and the ratio of N3 to omega-6 polyunsaturated fatty acids (N3: N6), decreased in both MDD and SCH patients. Meanwhile, levels of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) decreased in SCH patients, and there was a significant difference in the composition of MCFAs and LCFAs between MDD and SCH patients. Moreover, the top 10 differential molecules could distinguish the two groups of diseases from HC and each other with high reliability. Conclusions: This study provides a further understanding of dysfunctional Trp and FA metabolism in adult patients with SCH or MDD and might develop combinatorial classifiers to distinguish between these disorders.
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Transtorno Depressivo Maior , Ácidos Graxos Ômega-3 , Esquizofrenia , Humanos , Adulto , Triptofano , Reprodutibilidade dos Testes , Ácidos Graxos/metabolismoRESUMO
Purpose: Timely and moderate luteinizing hormone (LH) secretion plays critical roles in follicle development and maturation. However, the role of LH supplementation in in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) cycles remains unclear. Can LH supplementation improve the clinical outcomes of patients who receive long-acting gonadotropin-releasing hormone agonist (GnRHa) pituitary downregulation in IVF/ICSI-ET cycles? Patients and Methods: This is a retrospective cohort study of 2600 long-acting GnRHa down-regulated IVF/ICSI cycles from 2017 to 2020 in our reproductive medicine centre of Nanjing Drum Tower Hospital. Total cycles were divided into two groups according to LH supplementation or not. In addition, we conducted a secondary analysis that used propensity-score matching to reduce the effects of confounding. Results: Exogenous LH addition was not significantly correlated with the clinical pregnancy rate (OR=0.910, 95% CI: 0.623-1.311, p=0.61) in logistic regression analysis. After propensity-score matching, we also found no significant association between LH supplementation and the clinical pregnancy rate (OR=0.792, 95% CI: 0.527-1.191, p=0.26). Conclusion: There is no obvious effect of exogenous LH supplementation on the clinical pregnancy rate in non-selective patients receiving long-acting GnRHa IVF/ICSI-ET cycles, which suggests that exogenous LH addition is not always needed, which can help us avoid drug overuse to a certain extent.
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Research question: The relationship between serum progesterone (P) and luteinizing hormone (LH) levels on the human chorionic gonadotropin (hCG) trigger day and the clinical pregnancy outcomes in modified natural frozen-thawed embryo transfer (mNC-FET) cycles are controversial. Design: This was a retrospective study of 788 mNC-FET cycles. A smooth fitting curve and threshold effect analysis was performed to identify the effect of serum P and LH levels measured on the hCG day on the clinical pregnancy rate (CPR) and live birth rate (LBR) of mNC-FET cycles. Results: The CPR and LBR decreased significantly when the LH level on the hCG day was greater than or equal to 32 IU/L. Further subgroup analysis showed that the CPR decreased significantly when the P level on the hCG day was equal to or greater than 1 ng/mL. When the P level was lower (< 1 ng/mL), the patients with an LH level greater than or equal to 32 IU/L had reduced CPR and LBR in mNC-FET cycles. Conclusion: Applying the hCG trigger on a day with a higher P level (≥ 1 ng/mL) leads to a decreased CPR and LBR. hCG administration with a higher LH level (≥ 32 IU/L) also leads to a decreased CPR and LBR in mNC-FET cycles when the P level is less than 1 ng/mL.
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Resultado da Gravidez , Progesterona , Gravidez , Feminino , Humanos , Estudos Retrospectivos , Transferência Embrionária , Gonadotropina Coriônica , Hormônio LuteinizanteRESUMO
A 52-year-old woman complained of inguinal lymph node enlargement, low fever and night sweats for 20 days. After pathological biopsy and metagenomic sequencing, she was diagnosed as having Bartonella henselae infection. Her lymph nodes were accompanied by multiple ulcers in the affected area and sinus formation. Azithromycin was administered according to the Sanford Guide to Antimicrobial Therapy 2020, combined with wound repair and partial resection of inguinal lymph nodes. The patient showed good recovery after the operation. In all, lymphadenitis associated with B. henselae infection is difficult to diagnose. Lymphadenitis with suppuration and sinus formation needs multidisciplinary consultation. When the causal pathogen is unknown, metagenomic sequencing is recommended for a definite diagnosis.
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BACKGROUND: Acute pancreatitis is the most common and severe complication of endoscopic retrograde cholangiopancreatography (ERCP). Recent evidence suggests that combinations based on rectal nonsteroidal anti-inflammatory drugs (NSAIDs) are more beneficial in preventing post-ERCP pancreatitis (PEP). Randomized controlled trials (RCTs) have also demonstrated the efficacy of glyceryl trinitrate (GTN). We conducted a network meta-analysis to compare NSAIDs and GTN for prevention of PEP and to determine whether they are better in combination. AIM: To compare NSAIDs and GTN for prevention of PEP and to determine whether they are better in combination. METHODS: A systematic search was done for full-text RCTs of PEP in PubMed, Embase, Science Citation Index, and the Cochrane Controlled Trials database. Inclusion and exclusion criteria were used to screen for eligible RCTs. The major data were extracted by two independent reviewers. The frequentist model was used to conduct this network meta-analysis and obtain the pairwise OR and 95%CI. The data were then extracted and assessed on the basis of the Reference Citation Analysis (https://www.referencecitationanalysis.com/). RESULTS: Twenty-four eligible RCTs were selected, evaluating seven preventive strategies in 9416 patients. Rectal indomethacin 100 mg plus sublingual GTN (OR: 0.21, 95%CI: 0.09-0.50), rectal diclofenac 100 mg (0.34, 0.18-0.65), sublingual GTN (0.34, 0.12-0.97), and rectal indomethacin 100 mg (0.49, 0.33-0.73) were all more efficacious than placebo in preventing PEP. The combination of rectal indomethacin and sublingual GTN had the highest surface under the cumulative ranking curves (SUCRA) probability of (92.2%) and was the best preventive strategy for moderate-to-severe PEP with a SUCRA probability of (89.2%). CONCLUSION: Combination of rectal indomethacin 100 mg with sublingual GTN offered better prevention of PEP than when used alone and could alleviate the severity of PEP.