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Tumor-associated macrophages (TAMs) take on pivotal and complex roles in the tumor microenvironment (TME); however, their heterogeneity in the TME remains incompletely understood. ETS proto-oncogene 1 (ETS1) is a transcription factor that is mainly expressed in lymphocytes. However, its expression and immunoregulatory role in colorectal cancer (CRC)-associated macrophages remain unclear. In the study, the expression levels of ETS1 in CD68+ macrophages in the CRC microenvironment were significantly higher than those in matched para-carcinoma tissues. Importantly, ETS1 increased the levels of chemokines C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 10 (CXCL10) in lipopolysaccharide-stimulated THP-1 cells. It also boosted the migration and invasion of CRC cells during the in vitro co-culture. In ETS1 conditional knockout mouse model, ETS1 deficiency in macrophages ameliorated the histological changes in DSS-induced ulcerative colitis mouse models and prolonged the survival in an azomethane/dextran sodium sulfate (AOM/DSS)-induced CRC model. ETS1 deficiency in macrophages substantially inhibited tumor formation, reduced F4/80+TIM4+ macrophages in the mesenteric lymph nodes, and decreased CCL2 and CXCL10 protein levels in tumor tissues. Moreover, ETS1 deficiency in macrophages effectively prevented liver metastasis of CRC and reduced the infiltration of TAMs into the metastasis sites. Subsequent studies have indicated that ETS1 upregulated the expression of T-cell immunoglobulin mucin receptor 4 in macrophages through the signal transducer and activator of transcription 1 signaling pathway activated by the autocrine action of CCL2/CXCL10. Collectively, ETS1 deficiency in macrophages potentiates antitumor immune responses by repressing CCL2 and CXCL10 expression, shedding light on potential therapeutic strategies for CRC.
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OBJECTIVE: To investigate the value of the pre-operative amide proton transfer-weighted (APTw) MRI to assess the prognostic factors in rectal adenocarcinoma (RA). METHODS: This prospective study ran from January 2022 to September 2023 and consecutively enrolled participants with RA who underwent pre-operative MRI and radical surgery. The APTw signal intensity (SI) values of RA with various tumor (T), node (N) stages, perineural invasion (PNI), and tumor grade were compared by Mann-Whitney U-test or t-test. The receiver operating characteristic curve was used to evaluate the diagnostic performance of the APTw SI values. RESULTS: A total of 51 participants were enrolled (mean age, 58 years ± 10 [standard deviation], 26 men). There were 24 in the T1-T2 stage and 9 with positive PNI. The APTw SI max, 99th, and 95th values were significantly higher in T3-T4 stage tumor than in T1-T2; the median (interquartile range) (M (IQR)) was (4.0% (3.6-4.9%) vs 3.4% (2.9- 4.3%), p = 0.017), (3.7% (3.2-4.1%) vs 3.2% (2.8-3.8%), p = 0.013), and (3.3% (2.8-3.8%) vs 2.9% (2.3-3.5%), p = 0.033), respectively. These indicators also differed significantly between the PNI groups, with the M (IQR) (4.5% (3.6-5.7%) vs 3.7% (3.2-4.2%), p = 0.017), (4.1% (3.4-4.8%) vs 3.3% (3.0-3.9%), p = 0.022), and (3.7% (2.7-4.2%) vs 2.9% (2.6-3.5%), p = 0.045), respectively. CONCLUSION: Pre-operative APTw MRI has potential value in the assessment of T-staging and PNI determination in RA. CLINICAL RELEVANCE STATEMENT: Pre-operative amide proton transfer-weighted MRI provides a quantitative method for noninvasive assessment of T-staging and PNI in RA aiding in precision treatment planning. KEY POINTS: The efficacy of APTw MRI in RA needs further investigation. T3-T4 stage and PNI positive APTw signal intensities were higher than T1-T2 and non-PNI, respectively. APTw MRI provides a quantitative method for assessment of T staging and PNI in RA.
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BACKGROUND: Central nervous system involvement in chronic lymphocytic leukemia rarely occurs, and there is no standard therapy for central nervous system involvement in chronic lymphocytic leukemia. This article aims to analyze the diagnosis and treatment of central nervous system involvement in chronic lymphocytic leukemia. CASE PRESENTATION: It reports two cases of central nervous system involvement in chronic lymphocytic leukemia describing the clinical course, therapy, and prognosis. Case 1 is a 67-year-old Asian male patient, he experienced complications with central nervous system involvement after developing resistance to ibrutinib, bendamustine, and rituximab (BR) chemotherapies. The central nervous system lesion was controlled with high-dose methotrexate combined with pomalidomide, but Richter transformation occurred several months later. Case 2 is a 62-year-old Asian female patient, she had central nervous system involvement at initial diagnosis, and bone marrow and central nervous system lesions were controlled by ibrutinib therapy. CONCLUSION: Central nervous system involvement in chronic lymphocytic leukemia is rare and can be diagnosed on the basis of clinical features, cerebrospinal fluid testing, and radiographic evaluation. Ibrutinib, pomalidomide, and other drugs that can cross the blood-brain barrier may be effective for treating central nervous system involvement in chronic lymphocytic leukemia.
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Adenina , Leucemia Linfocítica Crônica de Células B , Piperidinas , Talidomida , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Idoso , Masculino , Feminino , Pessoa de Meia-Idade , Adenina/análogos & derivados , Piperidinas/uso terapêutico , Talidomida/uso terapêutico , Talidomida/análogos & derivados , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/secundário , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Pirazóis/uso terapêutico , Metotrexato/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pirimidinas/uso terapêuticoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Sinisan formula (SNSF), documented in the classic books Shanghan Lun, is known for its ability to regulate liver-qi and treat depression. However, its underlying mechanism, particularly its effects on dynamic real-time neuron activity and circuits remains to be fully elucidated. AIM OF THE STUDY: This study aimed to investigate the antidepressant effect of SNSF and its central nervous system mechanism on depression-like behaviors, focusing on the prefrontal cortex (PFC) to dorsal raphe nucleus (DRN) neural circuit in a stress-induced adolescent animal model. MATERIALS AND METHODS: SNSF comprised four herbs, the root of Bupleurum chinense DC., the root of Paeonia lactiflora Pall., the fruit of Citrus aurantium L., the rhizome of Glycyrrhiza uralensis Fisch., in equal propotions. The adolescent depression animal model was induced by maternal separation (MS) and chronic restraint stress (CRS). In-vivo multichannel physiological electrodes were implanted into the PFC on PND 28 and animals were recorded 5 times during PND 35-46. From PND 47, the behavioral tests were performed to evaluate the antidepressant efficacy of SNSF. Subsequently, brain tissue was collected for Western blot and immunofluorescence staining analysis. Retro virus was injected into the DRN to explore sources of projections received by serotonergic (5-HTergic) neurons. And the PFC-to-DRN circuit was activated or inhibited through chemogenetic techniques to investigate the effects of SNSF on depression-like behaviors. RESULTS: Administration of SNSF for 18 days effectively alleviated depression-like behaviors in MS&CRS adolescent mice. The PFC emerged as the primary glutamatergic projection source of the DRN5-HT neurons. Following SNSF administration for 13/15/18 days, there was an increase in the firing rate of excitatory neurons and excitatory/inhibitory (E/I) ratio in the PFC. MS&CRS stress let to a reduction in the density of 5-HT+ and CaMKII + neurons in the DRN, accompanied by an increase in the density of GAD + neurons in the DRN, while SNSF administration reversed the alterations. Chemogenetic activation of the PFC-to-DRN circuit rescued the depression-like behaviors induced by MS&CRS, whereas suppression of this circuit attenuated the antidepressant effect of SNSF. CONCLUSIONS: SNSF significantly mitigated depression-like behaviors in MS&CRS mice. SNSF exerts its antidepressant effects by increasing the E/I ratio in the PFC and enhancing glutamatergic projections from the PFC to the DRN.
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Antidepressivos , Depressão , Núcleo Dorsal da Rafe , Medicamentos de Ervas Chinesas , Córtex Pré-Frontal , Animais , Núcleo Dorsal da Rafe/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Antidepressivos/farmacologia , Masculino , Depressão/tratamento farmacológico , Camundongos , Medicamentos de Ervas Chinesas/farmacologia , Modelos Animais de Doenças , Estresse Psicológico/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Vias Neurais/efeitos dos fármacos , Privação MaternaRESUMO
OBJECTIVE: To investigate the effect of incorporating noise-canceling headphones into the delivery process for natural childbirth puerperae. METHODS: We conducted a retrospective analysis of clinical data encompassing natural childbirth puerperae in the People's Hospital of Suzhou New District from January 2021 to February 2023. The implementation of routine noise reduction management was done from January 2021 to January 2022. During this interval, 69 natural childbirth puerperae were selected as subjects, with 7 excluded, resulting in 62 participants constituting the reference group. Subsequently, noise-canceling headphones were distributed to natural childbirth puerperae from February 2022 to February 2023. In this phase, 66 subjects were selected, and 6 were excluded, resulting in 60 participants forming the observation group. Following admission, both groups underwent corresponding nursing management. Emotional states, pain levels, and various indicators were systematically collected and meticulously compared. RESULTS: The observation group exhibited significantly lower Hamilton Anxiety Rating Scale scores than the reference group before delivery and during the first stage of labor (P < 0.05). The observation group demonstrated significantly lower visual analog scale scores and substance P, nitric oxide, and prostaglandin E2 levels than the reference group during the first stage of labor (P < 0.001). During the second stage of labor, the visual analog) scale scores were significantly lower in the observation group than in the reference group (P < 0.05). The durations of first and second labor stages were significantly shorter in the observation group than in the reference group (P < 0.05). No significant difference existed in Apgar scores between the two groups (P > 0.05). CONCLUSION: The utilization of noise-canceling headphones emerges as an effective intervention, alleviating anxiety, reducing pain during T1, and abbreviating total labor time in natural childbirth puerperae, suggesting its substantial clinical application value and potential as a beneficial addition to maternity care practices.
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Parto Normal , Ruído , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Adulto , Parto Normal/métodos , Ruído/efeitos adversos , Parto Obstétrico/métodos , Dispositivos de Proteção das Orelhas , Ansiedade/prevenção & controle , Ansiedade/etiologiaRESUMO
BACKGROUND: Neuropathic pain remains a formidable challenge for modern medicine. The first-line pharmacological therapies exhibit limited efficacy and unfavorable side effect profiles, highlighting an unmet need for effective therapeutic medications. The past decades have witnessed an explosion in efforts to translate epigenetic concepts into pain therapy and shed light on epigenetics as a promising avenue for pain research. Recently, the aberrant activity of histone deacetylase (HDAC) has emerged as a key mechanism contributing to the development and maintenance of neuropathic pain. AIMS: In this review, we highlight the distinctive role of specific HDAC subtypes in a cell-specific manner in pain nociception, and outline the recent experimental evidence supporting the therapeutic potential of HDACi in neuropathic pain. METHODS: We have summarized studies of HDAC in neuropathic pain in Pubmed. RESULTS: HDACs, widely distributed in the neuronal and non-neuronal cells of the dorsal root ganglion and spinal cord, regulate gene expression by deacetylation of histone or non-histone proteins and involving in increased neuronal excitability and neuroinflammation, thus promoting peripheral and central sensitization. Importantly, pharmacological manipulation of aberrant acetylation using HDAC-targeted inhibitors (HDACi) has shown promising pain-relieving properties in various preclinical models of neuropathic pain. Yet, many of which exhibit low-specificity that may induce off-target toxicities, underscoring the necessity for the development of isoform-selective HDACi in pain management. CONCLUSIONS: Abnormally elevated HDACs promote neuronal excitability and neuroinflammation by epigenetically modulating pivotal gene expression in neuronal and immune cells, contributing to peripheral and central sensitization in the progression of neuropathic pain, and HDACi showed significant efficacy and great potential for alleviating neuropathic pain.
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Epigênese Genética , Inibidores de Histona Desacetilases , Histona Desacetilases , Neuralgia , Humanos , Epigênese Genética/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/metabolismo , Neuralgia/tratamento farmacológico , Neuralgia/metabolismoRESUMO
Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.
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Background: Hypertension stands as the leading single contributor to the worldwide burden of mortality and disability. Limited evidence exists regarding the association between the combined healthy lifestyle score (HLS) and hypertension control in both treated and untreated hypertensive individuals. Therefore, we aimed to investigate the association between HLS and hypertension control among adults with treated and untreated hypertension. Methods: This cross-sectional study, including 311,994 hypertension patients, was conducted in Guangzhou using data from the National Basic Public Health Services Projects in China. The HLS was defined based on five low-risk lifestyle factors: healthy dietary habits, active physical activity, normal body mass index, never smoking, and no alcohol consumption. Controlled blood pressure was defined as systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg. A multivariable logistic regression model was used to assess the association between HLS and hypertension control after adjusting for various confounders. Results: The HLS demonstrated an inverse association with hypertension control among hypertensive patients. In comparison to the low HLS group (scored 0-2), the adjusted odds ratios (95% confidence intervals) for hypertension were 0.76 (0.74, 0.78), 0.59 (0.57, 0.60), and 0.48 (0.46, 0.49) for the HLS groups scoring 3, 4, and 5, respectively (Ptrend < 0.001). Notably, an interaction was observed between HLS and antihypertensive medication in relation to hypertension control (Pinteraction < 0.001). When comparing the highest HLS (scored 5) with the lowest HLS (scored 0-2), adjusted odds ratios (95% confidence intervals) were 0.50 (0.48, 0.52, Ptrend < 0.001) among individuals who self-reported using antihypertensive medication and 0.41 (0.38, 0.44, Ptrend < 0.001) among those not using such medication. Hypertensive patients adhering to a healthy lifestyle without medication exhibited better blood pressure management than those using medication while following a healthy lifestyle. Conclusion: HLS was associated with a reduced risk of uncontrolled blood pressure.
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Anti-Hipertensivos , Hipertensão , Adulto , Humanos , Anti-Hipertensivos/uso terapêutico , Estudos Transversais , Hipertensão/tratamento farmacológico , Pressão Sanguínea , Estilo de Vida SaudávelRESUMO
Schizosaccharomyces pombe is a commonly utilized model organism for studying various aspects of eukaryotic cell physiology. One reason for its widespread use as an experimental system is the ease of genetic manipulations, leveraging the natural homology-targeted repair mechanism to accurately modify the genome. We conducted a study to assess the feasibility and efficiency of directly introducing exogenous genes into the fission yeast S. pombe using Polymerase Chain Reaction (PCR) with short-homology flanking sequences. Specifically, we amplified the NatMX6 gene (which provides resistance to nourseothricin) using PCR with oligonucleotides that had short flanking regions of 20 bp, 40 bp, 60 bp and 80 bp to the target gene. By using this purified PCR product, we successfully introduced the NatMX6 gene at position 171 385 on chromosome III in S. pombe. We have made a simple modification to the transformation procedure, resulting in a significant increase in transformation efficiency by at least 5-fold. The success rate of gene integration at the target position varied between 20% and 50% depending on the length of the flanking regions. Additionally, we discovered that the addition of dimethyl sulfoxide and boiled carrier DNA increased the number of transformants by ~60- and 3-fold, respectively. Furthermore, we found that the removal of the pku70+ gene improved the transformation efficiency to ~5% and reduced the formation of small background colonies. Overall, our results demonstrate that with this modified method, even very short stretches of homologous regions (as short as 20 bp) can be used to effectively target genes at a high frequency in S. pombe. This finding greatly facilitates the introduction of exogenous genes in this organism.
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Background: Cardiometabolic multimorbidity (CMM) has emerged as a prominent public health concern. Hypertensive patients are prone to develop comorbidities. Moreover, the accumulation of visceral adipose tissue is the main cause for the development of cardiometabolic diseases. The cardiometabolic index (CMI), lipid accumulation product (LAP), visceral adiposity index (VAI), and Chinese visceral adiposity index (CVAI) not only assess adipose tissue mass but also reflect adipose tissue dysfunction. So far, no study has been reported to evaluate the association of CMI, LAP, VAI, and CVAI with CMM risk in hypertensive patients. Therefore, this study aimed to assess the association between these adiposity indicators and the risk of CMM among Chinese hypertensive patients. Methods: In this cross-sectional study, a total of 229,287 hypertensive patients aged 35 years and older were included from the National Basic Public Health Service Project. All participants underwent a face-to-face questionnaire survey, physical examination, and the collection of fasting venous blood samples. Multivariable logistic regression models were performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Receiver operating characteristic curve was utilized to evaluate the identification ability for CMM. Results: After adjusting for confounders, each 1-standard deviation increase in CMI, LAP, VAI, and CVAI was associated with a 14%, 8%, 12%, and 54% increased risk of CMM, respectively. When comparing the highest quartile of these indicators with the lowest quartile, individuals in the highest quartile of CMM, LAP, VAI, and CVAI had a 1.39-fold (95% CI 1.30, 1.48), 1.28-fold (95% CI 1.19, 1.37), 1.37-fold (95% CI 1.29, 1.46), and 2.56-fold (95% CI 2.34, 2.79) increased risk of CMM after adjusting for potential confounders. Notably, a nonlinear association was observed for CMI, LAP, and VAI with the risk of CMM (all P nonlinearity < 0.001). CVAI exhibited the highest area under the receiver operating characteristic curve (AUC) among all the included adiposity indices in this analysis. Conclusion: This study indicated the significant positive association of CMI, LAP, VAI, and CVAI with the risk of CMM in hypertensive patients. Among these indicators, CVAI demonstrated the most robust performance in predicting CMM risk and may serve as a valuable tool for identifying CMM risk in Chinese hypertensive patients.
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Adiposidade , Hipertensão , Humanos , Estudos Transversais , Multimorbidade , Índice de Massa Corporal , Obesidade , Hipertensão/epidemiologia , Obesidade AbdominalRESUMO
Setaria italica is an important crop in China that plays a vital role in the Chinese dietary structure. In the last several decades, high temperature has become the most severe climate issue in the world, which causes great harm to the yield and quality formation of millet. In this study, two main cultivated varieties (ZG2 and AI88) were used to explore the photosynthesis and yield index of the whole plant under heat stress. Results implied that photosynthesis was not inhibited during the heat stress, and that the imbalance in sugar transport between different tissues may be the main factor that affects yield formation. In addition, the expression levels of seven SiSUT and twenty-four SiSWEET members were explored. Sugar transporters were heavily affected during the heat stress. The expression of SiSWEET13a was inhibited by heat stress in the stems, which may play a vital role in sugar transport between different tissues. These results provide new insights into the yield formation of crops under heat stress, which will provide guidance to crop breeding and cultivation.
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Setaria (Planta) , Setaria (Planta)/genética , Setaria (Planta)/metabolismo , Melhoramento Vegetal , Perfilação da Expressão Gênica , Resposta ao Choque Térmico/genética , Açúcares/metabolismo , Estresse Fisiológico/genética , Regulação da Expressão Gênica de PlantasRESUMO
NAC transcription factors regulate plant growth, development, and stress responses. However, the number, types, and biological functions of Limonium bicolor LbNAC genes have remained elusive. L. bicolor secretes excessive salt ions through salt glands on its stems and leaves to reduce salt-induced damage. Here, we identiï¬ed 63 NAC members (LbNAC1-63) in L. bicolor, which were unevenly distributed across eight chromosomes. Cis-elements in the LbNAC promoters were related to growth and development, stress responses, and phytohormone responses. We observed strong colinearity between LbNACs and GmNACs from soybean (Glycine max). Thus, LbNAC genes may share similar functions with GmNAC genes. Expression analysis indicated that 16 LbNAC genes are highly expressed in roots, stems, leaves, and flowers, whereas 17 LbNAC genes were highly expressed throughout salt gland development, suggesting that they may regulate this developmental stage. Silencing LbNAC54 in L. bicolor decreased salt gland density, salt secretion from leaves, and overall salt tolerance. In agreement, genes related to salt gland development were significantly downregulated in LbNAC54-silenced lines. Our ï¬ndings shed light on LbNAC genes and help elucidate salt gland development and salt secretion in L. bicolor. Our data also provide insight into NAC functions in halophytes.
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Plumbaginaceae , Plantas Tolerantes a Sal , Plantas Tolerantes a Sal/genética , Plantas Tolerantes a Sal/metabolismo , Plumbaginaceae/genética , Plumbaginaceae/metabolismo , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Folhas de Planta/metabolismo , Glycine max , Regulação da Expressão Gênica de Plantas , FilogeniaRESUMO
To evaluate the potential ecotoxicity of ethiprole and early warning to earthworms (Eisenia fetida), different concentrations (0 mg·kg-1, 416 mg·kg-1, 625 mg·kg-1, and 1000 mg·kg-1) of ethiprole were added to artificial soil. The key bioindicators were measured and screened at 3 days, 7 days, 14 days, 21 days, and 28 days. The results show that the activity of catalase (CAT) was inhibited for all treatments during the whole exposure period. Besides, the olive tail moment (OTM) value increased gradually as the concentration got higher, which exhibited a dose-time-dependent relationship. Superoxide dismutase (SOD) gene reached the maximum on the 7th day. Mitochondrial large ribosomal RNA (l-rRNA) subunit gene was always in a downregulated state as the concentration increased. Our results show that different concentrations of ethiprole induced certain oxidative stress, DNA damage, and genotoxicity in earthworms. The CAT activity, OTM, and SOD gene could be the most sensitive biomarkers to monitor the toxicity of ethiprole in the soil.
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Dano ao DNA , Oligoquetos , Estresse Oxidativo , Animais , Oligoquetos/efeitos dos fármacos , Oligoquetos/genética , Estresse Oxidativo/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Poluentes do Solo/toxicidade , Superóxido Dismutase/metabolismo , Catalase/metabolismoRESUMO
This systematic review was carried out to describe QoL and resilience in infertile patients, as well as the relationship between them, and to give a theoretical foundation for clinical practice. The databases of CNKI, Wanfang data, VIP database, PubMed, Web of Science, and Embase were searched without a time limit. A narrative synthesis of relevant articles was undertaken. This systematic review was registered on PROSPERO in advance. Of 21 studies eligible for inclusion in this review, 13 focused on the relationship between QoL and resilience, 5 on QoL influencing factors (resilience included), and 3 on mediation effect analysis on mental health (resilience as a mediator). Resilience can significantly predict the QoL of infertile patients. It seems plausible that more resilient couples will be less vulnerable to the stress of infertility. A global consortium of infertile population research could make cross-cultural comparisons of QoL and resilience possible. Future research should focus on resilience therapies. Systematic review registration: This systematic review was registered on PROSPERO in advance (CRD42023414706).
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Infertilidade , Qualidade de Vida , Resiliência Psicológica , Humanos , Qualidade de Vida/psicologia , Infertilidade/psicologia , Feminino , MasculinoRESUMO
BACKGROUND: Neuropathic pain is a prevalent and highly debilitating condition that impacts millions of individuals globally. Neuroinflammation is considered a key factor in the development of neuropathic pain. Accumulating evidence suggests that protein tyrosine phosphatase 1B (PTP1B) plays a crucial role in regulating neuroinflammation. Nevertheless, the specific involvement of PTP1B in neuropathic pain remains largely unknown. This study aims to examine the impact of PTP1B on neuropathic pain and unravel the underlying molecular mechanisms implicated. METHODS: In the current study, we evaluated the paw withdrawal threshold (PWT) of male rats following spared nerve injury (SNI) to assess the presence of neuropathic pain. To elucidate the underlying mechanisms, western blotting, immunofluorescence, and electron microscopy techniques were employed. RESULTS: Our results showed that SNI significantly elevated PTP1B levels, which was accompanied by an increase in the expression of endoplasmic reticulum (ER) stress markers (BIP, p-PERK, p-IRE1α, and ATF6) and phosphorylated NF-κB in the spinal dorsal horn. SNI-induced mechanical allodynia was impaired by the treatment of intrathecal injection of PTP1B siRNA or PTP1B-IN-1, a specific inhibitor of PTP1B. Moreover, the intrathecal administration of PTP1B-IN-1 effectively suppressed the expression of ER stress markers (BIP, p-PERK/p-eIF2α, p-IRE1α, and ATF6), leading to the inhibition of NF-κB, microglia, and astrocytes activation, as well as a decrease in pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1ß. However, these effects were reversed by intrathecal administration of tunicamycin (Tm, an inducer of ER stress). Additionally, intrathecal administration of Tm in healthy rats resulted in the development of mechanical allodynia and the activation of NF-κB-mediated neuroinflammatory signaling. CONCLUSIONS: The upregulation of PTP1B induced by SNI facilitates the activation of NF-κB and glial cells via ER stress in the spinal dorsal horn. This, in turn, leads to an increase in the production of pro-inflammatory cytokines, thereby contributing to the development and maintenance of neuropathic pain. Therefore, targeting PTP1B could be a promising therapeutic strategy for the treatment of neuropathic pain.
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NF-kappa B , Neuralgia , Animais , Masculino , Ratos , Citocinas , Estresse do Retículo Endoplasmático , Endorribonucleases/uso terapêutico , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Neuralgia/metabolismo , Neuroglia/metabolismo , Doenças Neuroinflamatórias , Proteínas Serina-Treonina Quinases , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 1/uso terapêutico , Ratos Sprague-Dawley , Subunidade p50 de NF-kappa B/metabolismoRESUMO
BACKGROUND: Marginal zone lymphoma (MZL) is an indolent subtype of non-Hodgkin lymphoma (NHL), which is rare clinically with severe rashes as the initial symptom. CASE SUMMARY: This study reports a case of MZL with generalized skin rashes accompanied by pruritus and purulent discharge. First-line treatment with rituximab combined with zanubrutinib had poor effects. However, after switching to obinutuzumab combined with zanubrutinib, the case was alleviated, and the rashes disappeared. CONCLUSION: For patients with advanced stage MZL not benefiting from type I anti-CD20 monoclonal antibody (mAb) combination therapy, switching to a type II anti-CD20 mAb combination regimen may be considered. This approach may provide a new perspective in the treatment of MZL.
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The impact of dietary saturated fatty acids (SFAs) on breast cancer risk may vary depending on their carbon chain lengths, attributable to the discrepancy in their dietary sources and biological activities. The associations between SFA subgroups classified by chain length and breast cancer risk remain controversial. In this case-control study, we aimed to investigate the association between the dietary intake of SFA subgroups, classified by chain lengths, and odds of breast cancer in China. This study included 1661 cases of breast cancer (confirmed as primary and histologically) and 1674 frequency-matched controls. Face-to-face interviews were used to collect basic information, while dietary intake information was obtained by a food frequency questionnaire. The unconditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs). All SFA subgroups were inversely associated with odds of breast cancer. The adjusted ORs (95% CIs) were 0.78 (0.61-0.99) for medium-chain SFAs, 0.50 (0.31-0.83) for long even-chain SFAs, 0.69 (0.54-0.88) for long odd-chain, and 0.67 (0.48-0.95) for very long-chain SFAs, respectively. In the restricted cubic spline (RCS) models, a non-linear M-shaped association was observed between long odd-chain SFAs and odds of breast cancer (Pnon-linearity = 0.007). However, the associations of medium-chain SFAs, long even-chain SFAs, and very long-chain SFAs did not reach statistical significance (Pnon-linearity > 0.05). No significant interactions were observed between all these four subgroups of SFAs and menopausal status or BMI. Our findings emphasize the significance of elucidating the associations of dietary SFAs according to chain lengths, providing insights into the etiology as well as the potential benefits of SFA-rich food intake in reducing the risk of breast cancer. Further prospective cohort studies and intervention studies are warranted to confirm these findings and identify the underlying mechanisms of the association between dietary SFAs and breast cancer.
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Neoplasias da Mama , Ácidos Graxos , Humanos , Feminino , Estudos Prospectivos , Fatores de Risco , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estudos de Casos e Controles , Ingestão de Alimentos , Gorduras na DietaRESUMO
OBJECTIVES: To observe the therapeutic efficacy of acupuncture and its effects on abdominal circumference, separation distance of rectus abdominis and quality of life in patients with postpartum diastasis recti abdominis on the basis of diastasis recti abdominis exercise. METHODS: A total of 87 postpartum women with diastasis recti abdominis were randomly divided into an observation group (44 cases) and a control group (43 cases) . The control group was treated with conventional diastasis recti abdominis rehabilitation exercise, including abdominal breathing training and supine leg lifting training, 3 times a day for 2 weeks. On the basis of the treatment in the control group, the observation group was treated with acupuncture at Zhongwan(CV 12), Qihai(CV 6)and bilateral Shenshu(BL 23), Daimai(GB 26), Daheng(SP 15), Zusanli (ST 36), etc., 30 min each time, once a day for 2 weeks. Before and after treatment, the separation distance of rectus abdominis, low back pain visual analogue scale (VAS) score, abdominal circumference and 36-item short form health survey questionnaire (SF-36) score in the two groups were compared, and the clinical effect was evaluated. RESULTS: After treatment, the separation distance of rectus abdominis, low back pain VAS scores, abdominal circumference of the two groups were lower than those before treatment(P<0.05), and the physiological function, physiological role, pain, mental health, emotional role, social function, energy, general health scores and total scores of SF-36 were higher than those before treatment(P<0.05); the separation distance of rectus abdominis, low back pain VAS score, abdominal circumference of the observation group were lower than those in the control group(P<0.05), the sub-item scores and total score of SF-36 of the observation group were higher than those in the control group(P<0.05).The effective rate of the observation group was 95.5% (42/44), which was higher than 79.1% (34/43) in the control group(P<0.05). CONCLUSIONS: Acupuncture combined with diastasis recti abdominis exercise can effectively relieve the low back pain of postpartum diastasis recti abdominis patients, promote the recovery of recti abdominis function, and improve the quality of life. The clinical effect is superior to diastasis recti abdominis exercise alone.
Assuntos
Terapia por Acupuntura , Diástase Muscular , Dor Lombar , Feminino , Humanos , Reto do Abdome , Qualidade de Vida , Período Pós-Parto , Diástase Muscular/terapiaRESUMO
Objective: To explore the clinical efficacy and safety of edaravone dexborneol combined with tirofiban in the treatment of acute cerebral infarction. Methods: This is a retrospective study. A total of 80 patients with acute cerebral infarction (ACI) treated in Cangzhou People's Hospital from March 2018 to December 2021 were selected, and randomly divided into the routine group(n=40) and intervention group(n=40) according to the principle of random draw. Neurological deficits in the two groups were evaluated and compared before and after treatment using the National Institutes of Health Stroke Scale (NIHSS). The quality of life of the patients was evaluated by the modified Rankin Scale (mRS). Results: Before treatment, NIHSS and mRS scores of the two groups were not statistically significant(p>0.05); the levels of Vmin and Qmin in the two groups showed no statistical significance(p>0.05); no statistical significance was found in CRP or IL-6 levels between the two groups(p>0.05). After treatment for 14 days, the NIHSS and mRS scores of the two groups both decreased, which was more significant in the intervention group(p<0.05); Vmin and Qmin levels increased in both groups, which was more obvious in the intervention group(p<0.05); CRP and IL-6 levels reduced in both groups, which was more remarkable in the intervention group(p<0.05). The incidences of relevant adverse drug reactions presented no differences between the two groups during treatment(p>0.05). Conclusion: Edaravone dexborneol combined with tirofiban in the treatment of ACI can effectively improve patients' neurological deficits, quality of life and cerebral blood flow, and reduce inflammatory factor levels, have significant clinical efficacy and high clinical treatment safety.
RESUMO
This study aimed to study 3-dimensional (3D) changes of hard and soft tissues of skeletal class II patients after 2-jaw surgery and genioplasty. 32 adult patients diagnosed with mandibular hypoplasia who underwent 2-jaw surgery of maxillary impaction, mandibular advancement and genioplasty were enrolled. Cone-beam computed tomography and 3D stereophotogrammetry was conducted 1 week before and 6 months after surgery. Dolphin imaging software was used to establish a 3D digitizing model and 3D measurement system. Paired t-test was performed to compare the values before and after surgery. Pearson's correlation test assessed the degree of correlations between hard and soft tissue change. The mean impaction of the maxilla was 2.600 ± 3.088 mm at A. The mean advancement of the mandible was 7.806 ± 2.647 mm at B. There was a significant upward and forward movement for most landmarks of the nose and lip, while a significant decrease in nasal tip height (lateral view), upper lip height, and upper and lower vermilion height. The nose's width was significantly increased. For maxillary, Sn, Ac-r, Ac-l, and Ls demonstrated a significant correlation with A and U1 in the anteroposterior axis. However, there were no significant correlations among them in the vertical axis. For mandibular, Li demonstrated a significant correlation with L1 in the anteroposterior axis specifically for the mandible. Notably, correlations between the landmarks of the chin's hard and soft tissues were observed across all axes. The utilization of 3-D analysis facilitated a quantitative comprehension of both hard and soft tissues, thereby furnishing valuable insights for the strategic formulation of orthognathic treatment plans targeting patients with skeletal class II conditions.