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OBJECTIVE: We designed this study to introduce the surgical strategy cerebrospinal fluid (CSF) decompression in treatment of Chiari malformation type I and compared CSF decompression with other surgical strategies to provide a solid basis for patient counseling. METHODS: The study enrolled 528 consecutive patients with CMI who underwent surgical interventions from 2012 to 2022. The surgical strategy for these patients was bony and dural decompression, anatomical reduction of herniated tonsils, or CSF decompression. Short-term results were determined after 3 months; long-term outcomes were evaluated at last follow-up (at least 18 months). RESULTS: CSF decompression was independently associated with better long- or short-term primary outcomes than anatomical reduction of herniated tonsils or bony and dural decompression (P < 0.001). Compared with short-term, the long-term outcomes were better in patients who underwent CSF decompression (P = 0.035), but were worse in patients with bony and dural decompression (P = 0.03). Specific surgical techniques cannot affect the long- and short-term outcomes of patients with Chiari malformation type I. CSF decompression provided better long-term syringomyelia improvement than short-term (181/218, 83% vs. 169/218, 77.5%; P < 0.001). CONCLUSIONS: CSF decompression, but not a specific surgical technique or operative method, was associated with favorable neurological outcomes in ADULT patients with Chiari malformation type I. The surgical technique and operative method should be selected according to the characteristics of each patient and the intraoperative condition to normalize CSF circulation at the craniovertebral junction area. The intraoperative target, smooth CSF flow out from the fourth ventricle and in to the bilateral Luschka foramina, could be observed.
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Background: Chronic obstructive pulmonary disease (COPD) is a respiratory disorder with a complex etiology involving genetic and environmental factors. The dysbiosis of gut microbiota has been implicated in COPD. Mendelian Randomization (MR) provides a tool to investigate causal links using genetic variants as instrumental variables. This study aims to employ MR analysis to explore the causal relationship between gut microbiota, lung function, and COPD. Methods: We utilized genome-wide association study (GWAS) data from MiBioGen, UK Biobank and FinnGen, which were related to gut microbial taxa, lung function parameters including forced vital capacity in one second (FEV1), forced vital capacity (FVC), and percentage of predicted FEV1 (FEV1%pred), as well as GWAS data for COPD. MR analysis was conducted to assess the causal effects of gut microbiota on lung function and the risk of COPD. Sensitivity analysis was utilized to examine the stability of the causal relationships. Multiple testing and reverse analysis were employed to evaluate the robustness of these relationships. Results: Using the IVW method, 64 causal correlations were identified. Through conducting sensitivity analysis, multiple testing, and reverse analysis, we identified 14 robust and stable causal relationships. The bacterial taxa that showed a positive association with lung function included Desulfovibrionaceae, Erysipelotrichales, Desulfovibrionales, Clostridiales, Clostridia, Deltaproteobacteria and Erysipelotrichia, while Selenomonadales and Negativicutes showed a negative association with lung function. The abundance of Holdemanella were positively correlated with the risk of COPD, while FamilyXIII exhibited a negative correlation with the risk of COPD. Conclusion: Several microbial taxa were discovered to have a positive causal correlation with lung function, offering potential insights into the development of probiotics. The presence of microbial taxa negatively correlated with lung function and positively correlated with COPD emphasized the potential impact of gut microbiota dysbiosis on respiratory health.
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Microbioma Gastrointestinal , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/genética , Análise da Randomização Mendeliana , Disbiose , Estudo de Associação Genômica Ampla , PulmãoRESUMO
In recent yearsï¼ regional compound air pollution events caused by fine particles ï¼PM2.5ï¼ and ozone ï¼O3ï¼ have occurred frequently in economically developed areas of Chinaï¼ in which atmospheric oxidizing capacity ï¼AOCï¼ has played an important role. In this studyï¼ the WRF-CMAQ model was used to study the impacts of anthropogenic emission reduction on AOC during the COVID-19 lockdown period. Three representative cities in eastern China ï¼Shijiazhuangï¼ Nanjingï¼ and Guangzhouï¼ were selected for an in-depth analysis to quantify the contribution of meteorology and emissions to the changes in AOC and oxidants and to discuss the impact of AOC changes on the formation of secondary pollutants. The results showed thatï¼ compared with that in the same period in 2019ï¼ the urban average AOC in Shijiazhuangï¼ Nanjingï¼ and Guangzhou in 2020 increased by 60%ï¼ 48.7%ï¼ and 12.6%ï¼ respectively. The concentrations of O3ï¼ hydroxyl radical ï¼·OHï¼ï¼ and nitrogen trioxide ï¼NO3·ï¼ increased by 1.6%-26.4%ï¼ 14.8%-73.3%ï¼ and 37.9%-180%ï¼ respectively. The AOC in the three cities increased by 0.06×10-4ï¼ 0.12×10-4ï¼ and 0.33×10-4 min-1ï¼ respectivelyï¼ due to emission reduction. The meteorological change increased AOC in Shijiazhuang and Nanjing by 20% and 17.9%ï¼ respectivelyï¼ but decreased AOC in Guangzhou by -9.3%. Enhanced AOC led to an increase in the nitrogen oxidation ratio ï¼NORï¼ and VOCs oxidation ratio ï¼VORï¼ and promoted the transformation of primary pollutants to secondary pollutants. This offset the effects of primary emission reduction and resulted in a nonlinear decline in secondary pollutants compared to emissions during the COVID-19 lockdown.
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Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Humanos , Poluentes Atmosféricos/análise , Material Particulado/análise , Controle de Doenças Transmissíveis , Poluição do Ar/análise , China , Oxirredução , Monitoramento Ambiental/métodosRESUMO
OBJECTIVE: To investigate the role of lncRNA AL645608.3 in the malignant progression of acute myeloid leukemia (AML) cells and explore relevant molecular mechanisms. METHODS: The expression level of AL645608.3 was measured in AML cell lines (THP-1, HL-60, KG-1, and AML-193) via real-time quantitative polymerase chain reaction (RT-qPCR). Small hairpin RNA (shRNA) and open reading frame of AL645608.3 were cloned into lentiviral vectors and were infected into THP-1 and AML-193 cells. The expression of casitas B-lineage lymphoma (CBL), interferon regulatory factor 6 (IRF6), and interferon beta 1 (IFNB1) was detected through RT-qPCR, and western blot. Co-immunoprecipitation (Co-IP) on IRF6 was conducted. Matrix metalloprotease-9 (MMP-9) activity was evaluated via gelatin zymography assay. RESULTS: LncRNA AL645608.3 was expressed in the four AML cell lines (THP-1, HL-60, KG-1, and AML-193). Silencing AL645608.3 mitigated the expression of IRF6 and IFNB1 but elevated the expression of CBL in THP-1 cells. Oppositely, AL645608.3 overexpression up-regulated the expression of IRF6 and IFNB1 but decreased the expression of CBL in AML-193 cells. Co-IP results proved that AL645608.3 could directly mediate IRF6 activity in THP-1 and AML-193 cells. MMP-9 activity was decreased by AL645608.3 knockdown and was improved by AL645608.3 overexpression in AML-193 cells. CONCLUSION: AL645608.3 is expressed in different AML cell lines, and mediates the expression of CBL, IRF6, IFNB1, and MMP-9. These findings might deepen our comprehension of the molecular mechanisms underlying AML.
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Objective: To investigate the clinical and pathologic features and diagnosis of follicular lymphoma (FL) with a predominantly diffuse growth pattern (DFL) with 1p36 deletion. Methods: Eight cases of DFL with 1p36 deletion diagnosed at Department of Pathology, Beijing Friendship Hospital, Capital Medical University (n=5) and the Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital (n=3) from January 2017 to January 2023 were included. Their clinicopathologic features and follow-up data were analyzed. Immunohistochemistry and fluorescence in situ hybridization (FISH) were performed. Results: There were five males and three females, with a median age of 67 years, and inguinal lymphadenopathy was found as the main symptom. Histologically, similar morphologic features were sheared among all cases, with effaced nodal structure and characterized by proliferation of centrocytes in a diffuse pattern, with or without follicular components. The germinal center-related markers such as CD10 and/or bcl-6 were expressed in the tumor cells, and 1p36 deletion but not bcl-2 translocation was appreciable in these cases. Conclusions: DFL with 1p36 deletion is a rare subtype of FL, with some overlaps with other types of FL or indolent B-cell lymphomas in their pathologic features. An accurate diagnosis requires comprehensive considerations based on their clinical, pathologic, immunohistochemical, and molecular features.
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Masculino , Feminino , Humanos , Idoso , Linfoma Folicular/patologia , Hibridização in Situ Fluorescente , Linfoma de Células B/patologia , Deleção Cromossômica , Proliferação de CélulasRESUMO
Objective:To explore the relationship between changes in levels of thrombomodulin (TM) and non high-density lipoprotein cholesterol (non-HDL-C) with ascending aortic elastic function and degree of coronary artery disease (CHD) in patients with coronary heart disease (CHD).Methods:A total of 147 patients with coronary heart disease diagnosed through coronary angiography at Yulin First Hospital from January 2018 to December 2022 were selected as the CHD group. In addition, 90 volunteers who underwent health examinations at our hospital and did not experience coronary artery disease were selected as the control group. Two groups were compared in terms of blood lipids [triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)], ascending aortic elastic function parameters [arterial dilation (AD), arterial stiffness index (ASI)], TM, non HDL-C levels, and other indicators, and stratified analysis was conducted according to the number of coronary lesions. The linear correlation analysis method was used to analyze the relationship between TM, non-HDL-C, Gensini score, and ascending aortic elastic function parameters.Results:The serum levels of TG, TC, LDL-C, TM, and non HDL-C in the CHD group were significantly higher than those in the control group, while the HDL-C levels were lower than those in the control group, with statistical significance (all P<0.05). The ASI of the ascending aorta in the CHD group was significantly higher than that in the control group, while the AD was lower than that in the control group, and the differences were statistically significant (all P<0.05). The serum levels of TG, TC, LDL-C, TM, and non HDL-C in CHD patients with multiple coronary artery lesions were significantly higher than those in patients with dual or single coronary artery lesions, and the HDL-C levels were lower than those in patients with dual or single coronary artery lesions, with statistical significance (all P<0.05); The serum levels of TM and non HDL-C in CHD patients with dual coronary artery disease were significantly higher than those in single coronary artery disease patients, and the HDL-C levels were lower than those in single coronary artery disease patients, with statistical significance (all P<0.05). The ASI of CHD patients with multiple coronary artery lesions was significantly higher than that of patients with dual or single coronary artery lesions, and the AD was lower than that of patients with dual or single coronary artery lesions, with statistical significance (all P<0.05); The ASI of CHD patients with dual coronary artery disease was significantly higher than that of patients with single coronary artery disease, and the AD was lower than that of patients with single coronary artery disease, with statistical significance (all P<0.05). The TM, non HDL-C levels in CHD patients were significantly negatively correlated with AD (all P<0.05), and positively correlated with ASI and Gensini scores (all P<0.05). Conclusions:The levels of TM and non HDL-C in CHD patients significantly increase, and the ascending aortic elasticity function was decreased. TM and non HDL-C are related to coronary elasticity function and the severity of coronary artery disease.
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Gastric cancer (GC) is a prominent global health issue, as it ranks as the fifth most prevalent type of cancer and the fourth most significant cause of cancer-related mortality worldwide. Although H. pylori is known to play a role in the development of GC, genetic factors also play a role in its onset and progression. Recent studies have shown that genetic polymorphisms are strongly associated with the development of GC and that certain single nucleotide polymorphisms (SNPs) can be used as biomarkers for early diagnosis and prevention. Epigenetic disturbances, such as DNA methylation, are involved in the development of GC, and mutations in the DNA methyltransferase (DNMT) gene have been found to increase the risk of GC. However, previous findings on the association between DNMTs SNPs and GC risk have been inconsistent. In this study, an updated meta-analysis of three well-studied and controversial DNMTs polymorphic loci, DNMT1 rs16999593, DNMT3A rs1550117 and DNMT3B rs1569686, was performed to provide more reliable results. It was found that DNMT1 rs16999593 was not associated with GC, DNMT3A rs1550117 may have a positive association with GC risk, and DNMT3B rs1569686 may be a protective factor for GC. These findings may provide valuable information for early diagnosis and prevention of GC, but further studies are needed to confirm these results.
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Predisposição Genética para Doença , Neoplasias Gástricas , Humanos , Genótipo , DNA Metiltransferase 3A , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferase 1/genética , Polimorfismo de Nucleotídeo Único , Metilação de DNA , Neoplasias Gástricas/genética , Fatores de ProteçãoRESUMO
Cucurbitacin B (CuB) is a member of the cucurbitacin family, which has shown potent anticancer pharmacological activity. Prolonged or severe endoplasmic reticulum stress (ERS) induces apoptosis; therefore, the present study investigated whether CuB may activate the ERS pathway to induce apoptosis. HT-29 and SW620 colorectal cancer (CRC) cells were treated with a range of concentrations of CuB for 48 h, and the viability and proliferation of cells were determined using Cell Counting Kit 8 (CCK8) and colony formation assays. Subsequently, the appropriate CuB concentration (5 µM) was selected for treatment of CRC cells for 48 h. Western blot analysis was used to measure the expression levels of ERS-related proteins, flow cytometry was used to evaluate apoptosis, the dichlorodihydrofluorescein diacetate fluorescent probe was used to detect reactive oxygen species (ROS) production, and the relationship between ROS and ERS was determined by western blot analysis. Furthermore, flow cytometry was used to evaluate apoptosis after treatment with the ERS inhibitor 4-phenylbutyric acid, the ROS inhibitor N-acetylcysteine and following knockdown of CHOP expression. In addition, western blot analysis was performed to measure Bax and Bcl2 protein expression levels, and a CCK8 assay was performed to evaluate the viability of cells following knockdown of CHOP. Notably, CuB treatment increased apoptosis and inhibited cell proliferation in CRC cell lines, and these effects were mediated by ROS and ROS-regulated activation of the PERK and XBP1 ERS pathways. In conclusion, CuB may induce apoptosis in HT-29 and SW620 CRC cells via ROS and ERS.
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BACKGROUND: Traumatic spinal cord injury (SCI) is still devastating. It was suggested that the inhibition of mTOR may alleviate neuronal inflammatory injury but its underlying mechanism remained to be elucidated. AIM2 (absent in melanoma 2) recruits ASC (apoptosis-associated speck-like protein containing a CARD) and caspase-1 to form the AIM2 inflammasome, activate caspase-1, and elicit inflammatory responses. We designed this study to elucidate whether pre-treatments of rapamycin could suppress SCI induced neuronal inflammatory injury via AIM2 signaling pathway in vitro and in vivo. METHODS: We performed oxygen and glucose deprivation / re-oxygenation (OGD) treatment and rats clipping model to mimic neuronal injury after SCI in vitro and in vivo. Morphologic changes of injured spinal cord were detected by hematoxylin and eosin staining. The expression of mTOR, p-mTOR, AIM2, ASC, Caspase-1 and et al were analyzed by fluorescent staining, western blotting or qPCR. The polarization phenotype of microglia was identified by flow cytometry or fluorescent staining. RESULTS: We found BV-2 microglia without any pre-treatment cannot alleviate primary cultured neuronal OGD injury. However, pre-treated rapamycin in BV-2 cells could transform microglia to M2 phenotype and protects against neuronal OGD injury via AIM2 signaling pathway. Similarly, pre-treatment of rapamycin could improve the outcome of cervical SCI rats through AIM2 signaling pathway. CONCLUSIONS: It was suggested that resting state microglia pre-treated by rapamycin could protect against neuronal injury via AIM2 signaling pathway in vitro and in vivo. Pre-inhibition of mTOR pathway may improve neuronal protection after SCI.
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Medula Cervical , Traumatismos da Medula Espinal , Ratos , Animais , Microglia/metabolismo , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Medula Cervical/metabolismo , Transdução de Sinais , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Medula Espinal/metabolismo , Caspase 1/metabolismo , Proteínas de Ligação a DNA/metabolismoRESUMO
BACKGROUND: Basilar invagination (BI) is a common disease in the craniocervical junction (CVJ) area. Posterior fossa decompression with/without fixation is a controversial surgical strategy for BI type B. This study aimed to evaluate the efficacy of simple posterior fossa decompression in treating BI type B. METHODS: This study retrospectively enrolled BI type B patients who underwent simple posterior fossa decompression at Huashan Hospital, Fudan University between 2014.12 and 2021.12. Patient data and images were recorded pre- and postoperatively (at the last follow-up) to evaluate the surgical outcomes and craniocervical stability. RESULTS: A total of 18 BI type B patients (13 females), with a mean age of 44.2±7.9 years (range 37-62 years), were enrolled. The mean follow-up period was 47.7±20.6 months (range 10-81 months). All patients received simple posterior fossa decompression without any fixation. At the last follow-up, compared with preoperation, the JOA scores were significantly higher (14.2±1.5 vs. 9.9±2.0, p = 0.001); the CCA was improved (128.7±9.6° vs. 121.5±8.1° p = 0.001), and the DOCL was reduced (7.9±1.5 mm vs. 9.9±2.5 mm, p = 0.001). However, the follow-up and preoperative ADI, BAI, PR, and D/L ratio were similar. No patients had an unstable condition between the C1-2 facet joints that was observed in the follow-up CT and dynamic X-ray. CONCLUSIONS: In BI type B patients, simple posterior fossa decompression could improve neurological function and will not induce CVJ instability in BI type B patients. Simple posterior fossa decompression could be a satisfactory surgical strategy for BI type B patients, but preoperative CVJ stability assessment is crucial.
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Articulação Atlantoaxial , Luxações Articulares , Lesões do Pescoço , Fusão Vertebral , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Descompressão Cirúrgica , Articulação Atlantoaxial/diagnóstico por imagem , Articulação Atlantoaxial/cirurgia , Luxações Articulares/cirurgia , Lesões do Pescoço/cirurgia , Resultado do TratamentoRESUMO
Cigarette smoking (CS) exposure-induced airway inflammatory responses drive the occurrence and development of emphysema and chronic obstructive pulmonary disease (COPD). However, its precise mechanisms have not been fully elucidated. In this study, we explore the role of Rab26 in CS exposure modulating the inflammatory response of airway epithelium and the novel mechanism of CS exposure regulation Rab26. These data showed that CS exposure and H2O2 (a type of ROS) suppressed the expression of Rab26 and increased the expression of DNMT3b in vivo and in vitro. GEO data analysis found the level of Rab26 was decreased in the lung tissue of COPD patients. CSE-induced ROS promoted DNA methylation of the Rab26 promoter and inhibited its promoter activity by elevating the DNMT3b level. Antioxidants N-Acetyl-l-cysteine (NAC), 5-Aza-2'-deoxycytidine (5-AZA) (DNA methylation inhibitor) and DNMT3B siRNA alleviated CSE's inhibitory effect on Rab26 expression in vitro. Importantly, NAC alleviated the improved expression of Rab26 and reduced DNMT3B expression, in the airway of smoking exposure as well as attenuated the inflammatory response in vivo. Overexpression of Rab26 attenuated CSE-induced production of inflammatory mediators through part inactivation of p38 and JNK MAPK. On the contrary, silencing Rab26 enhanced p38 and JNK activation and aggravated inflammatory response. These findings suggest that ROS-mediated Rab26 promoter hypermethylation is a critical step in cigarette smoking-induced airway epithelial inflammatory response. Restoring Rab26 in the airway epithelium might be a potential strategy for treating airway inflammation and COPD.
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Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Espécies Reativas de Oxigênio , Proteínas rab de Ligação ao GTP , Humanos , Fumar Cigarros/efeitos adversos , Metilação de DNA , Células Epiteliais/metabolismo , Peróxido de Hidrogênio/metabolismo , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Ventilator-induced lung injury (VILI) is a lung injury induced or aggravated by mechanical ventilation. Transforming growth factor (TGF)-ß1 is a cytokine that mediates immune function, enabling inflammatory attenuation and tissue repair. Here, we hypothesized that it plays an important role in the attenuation of VILI and inflammation. Ventilation with high tidal volume was performed on C57BL/6 mice to establish a VILI model. After 4 h of ventilation, mice were sacrificed (end of ventilation [EOV]) or extubated for resuscitation at 4 h (post-ventilation 4 h [PV4h]), 8 h (PV8h) and 24 h post-ventilation (PV1d). Recombinant mouse TGF-ß1 (rTGF-ß1) and the neutralization antibody of TGF-ß1 (nTAb) were used in vivo to examine the effect of TGF-ß1 on immune function and inflammatory attenuation in VILI mice. Lung injury was exacerbated at the same trend as the interleukin (IL)-1ß level, peaking at PV1d, whereas IL-6 and tumor necrosis factor (TNF)-α levels gradually reduced. Most active phagosomes, swollen round mitochondria, and cavitating lamellar bodies were observed at PV4h. The CD4+ T cells were significantly increased from PV4h to PV1d, and the CD8a + T cells were higher in the PV4h and PV1d groups; furthermore, the mice in the PV8h group showed highest proportion of CD4+CD8a+ T cells and CD4+/CD8a+ ratio. CD19 + and CD5 + CD19 + B cells in VILI mice began to increase at PV1d. The pulmonary expression of latent and monomer TGF-ß1 increased at PV4h and PV8h. Treatment of rTGF-ß1 only induced high expression of latent and monomer TGF-ß1 at EOV to decrease pulmonary levels of IL-1ß, IL-6, and TNF-α; however, lung injury attenuated from EOV to PV1d. TGF-ß1 induced the delayed elevation of CD4+/CD8a+ T cells ratio and activation of pulmonary CD4+CD8a+ double-positive T cells under certain conditions. Elastic fibers and celluloses, although relatively less proteoglycan, were observed with the overexpression of TGF-ß1 at PV4h and PV8h. In conclusion, TGF-ß1 attenuates the inflammatory response and lung injury of VILI via immune function regulation.
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Fator de Crescimento Transformador beta1 , Lesão Pulmonar Induzida por Ventilação Mecânica , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Interleucina-6/metabolismo , Camundongos Endogâmicos C57BL , Pulmão/patologia , Lesão Pulmonar Induzida por Ventilação Mecânica/patologia , Inflamação/metabolismo , ImunidadeRESUMO
BACKGROUND AND PURPOSE: Parvalbumin (PV)-positive neurons are a type of neuron in the lateral globus pallidus (LGP) which plays an important role in motor control. The present study investigated the effect of histamine on LGPPV neurons and motor behaviour. EXPERIMENTAL APPROACH: Histamine levels in LGP as well as its histaminergic innervation were determined through brain stimulation, microdialysis, anterograde tracing and immunostaining. Mechanisms of histamine action were detected by immunostaining, single-cell qPCR, whole-cell patch-clamp recording, optogenetic stimulation and CRISPR/Cas9 gene-editing techniques. The effect of histamine on motor behaviour was detected by animal behavioural tests. KEY RESULTS: A direct histaminergic innervation in LGP from the tuberomammillary nucleus (TMN) and a histamine-induced increase in the intrinsic excitability of LGPPV neurons were determined by pharmacological blockade or by genetic knockout of the histamine H1 receptor (H1 R)-coupled TWIK-related potassium channel-1 (TREK-1) and the small-conductance calcium-activated potassium channel (SK3), as well as by activation or overexpression of the histamine H2 receptor (H2 R)-coupled hyperpolarization-activated cyclic nucleotide-gated channel (HCN2). Histamine negatively regulated the STN â LGPGlu transmission in LGPPV neurons via the histamine H3 receptor (H3 R), whereas blockage or knockout of H3 R increased the intrinsic excitability of LGPPV neurons. CONCLUSIONS AND IMPLICATIONS: Our results indicated that the endogenous histaminergic innervation in the LGP can bidirectionally promote motor control by increasing the intrinsic excitability of LGPPV neurons through postsynaptic H1 R and H2 R, albeit its action was negatively regulated by the presynaptic H3 R, thereby suggesting possible role of histamine in motor deficits manifested in Parkinson's disease (PD).
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Histamina , Parvalbuminas , Animais , Globo Pálido/metabolismo , Neurônios , Receptores Histamínicos , Receptores Histamínicos H2/genética , Receptores Histamínicos H2/metabolismoRESUMO
The dorsolateral striatum (DLS) is the critical neural substrate that plays a role in motor control and motor learning. Our past study revealed a direct histaminergic projection from the tuberomammillary nucleus (TMN) of the hypothalamus to the rat striatum. However, the afferent of histaminergic fibers in the mouse DLS, the effect of histamine on DLS neurons, and the underlying receptor and ionic mechanisms remain unclear. Here, we demonstrated a direct histaminergic innervation from the TMN in the mouse DLS, and histamine excited both the direct-pathway spiny projection neurons (d-SPNs) and the indirect-pathway spiny projection neurons (i-SPNs) of DLS via activation of postsynaptic H1R and H2R, albeit activation of presynaptic H3R suppressed neuronal activity by inhibiting glutamatergic synaptic transmission on d-SPNs and i-SPNs in DLS. Moreover, sodium-calcium exchanger 3 (NCX3), potassium-leak channels linked to H1R, and hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) coupled to H2R co-mediated the excitatory effect induced by histamine on d-SPNs and i-SPNs in DLS. These results demonstrated the pre- and postsynaptic receptors and their downstream multiple ionic mechanisms underlying the inhibitory and excitatory effects of histamine on d-SPNs and i-SPNs in DLS, suggesting a potential modulatory effect of the central histaminergic system on the DLS as well as its related motor control and motor learning.
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Histamina , Neurônios , Animais , Camundongos , Corpo Estriado/metabolismo , Histamina/farmacologia , Neurônios/metabolismo , Canais de Potássio , Receptores Histamínicos H1/metabolismo , Transmissão SinápticaRESUMO
Introduction: Considering the role of bacteria in the onset of acute exacerbation of COPD (AECOPD), we hypothesized that the use of influenza-Streptococcus pneumoniae vaccination, oral probiotics or inhaled amikacin could prevent AECOPD. Methods: In this pilot prospective, muti-central, randomized trial, moderate-to-very severe COPD subjects with a history of moderate-to-severe exacerbations in the previous year were enrolled and assigned in a ratio of 1:1:1:1 into 4 groups. All participants were managed based on the conventional treatment recommended by GOLD 2019 report for 3 months, with three groups receiving additional treatment of inhaled amikacin (0.4 g twice daily, 5-7 days monthly for 3 months), oral probiotic Lactobacillus rhamnosus GG (1 tablet daily for 3 months), or influenza-S. pneumoniae vaccination. The primary endpoint was time to the next onset of moderate-to-severe AECOPD from enrollment. Secondary endpoints included CAT score, mMRC score, adverse events, and survival in 12 months. Results: Among all 112 analyzed subjects (101 males, 96 smokers or ex-smokers, mean ± SD age 67.19 ± 7.39 years, FEV1 41.06 ± 16.09% predicted), those who were given dual vaccination (239.7 vs. 198.2 days, p = 0.044, 95%CI [0.85, 82.13]) and oral probiotics (248.8 vs. 198.2 days, p = 0.017, 95%CI [7.49, 93.59]) had significantly delayed onset of next moderate-to-severe AECOPD than those received conventional treatment only. For subjects with high symptom burden, the exacerbations were significantly delayed in inhaled amikacin group as compared to the conventional treatment group (237.3 vs. 179.1 days, p = 0.009, 95%CI [12.40,104.04]). The three interventions seemed to be safe and well tolerated for patient with stable COPD. Conclusion: The influenza-S. pneumoniae vaccine and long-term oral probiotic LGG can significantly delay the next moderate-to-severe AECOPD. Periodically amikacin inhalation seems to work in symptomatic patients. The findings in the current study warrants validation in future studies with microbiome investigation.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT03449459.
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Objective: To investigate the clinicopathologic features of progressively transformed germinal center-like follicular T-cell lymphoma (PTGC-like FTCL). Methods: The clinicopathologic data of 14 PTGC-like FTCL cases that were diagnosed at the Beijing Friendship Hospital Affiliated to the Capital Medical University from January 2017 to January 2022 were retrospectively collected. Clinicopathological features, immunophenotype, and Epstein-Barr virus (EBV) infection status were analyzed in these cases. Polymerase chain reaction (PCR) was performed to detect the clonal gene rearrangements of T cell receptor (TCR) and the immunoglobulin (Ig) in 10 and 8 cases, respectively. Results: The male to female ratio was 5∶2. The median age was 61 years (range 32-70 years). All patients had lymphadenopathy at the time of diagnosis. By using the Ann Arbor system staging, seven cases were classified as stage Ⅰ-Ⅱ, and seven cases as stage Ⅲ-Ⅳ. Seven cases had B symptoms, four cases had splenomegaly, and two cases had skin rash and pruritus. Previously, three cases were diagnosed as classic Hodgkin's lymphoma, three cases as small B-cell lymphoma, two cases as atypical lymphoid hyperplasia unable to exclude angioimmunoblastic T-cell lymphoma (AITL), one case as EBV-associated lymphoproliferative disorder, and one case as peripheral T-cell lymphoma (PTCL) associated with the proliferation of B cells. All the 14 cases showed that the large nodules were composed of mature CD20+, IgD+B lymphocytes admixed with small aggregates of neoplastic cells with pale to clear cytoplasm. Moreover, hyperplastic germinal centers (GCs) and Hodgkin/Reed-Sternberg-like (HRS-like) cells were seen within these nodules in two and five cases, respectively. The neoplastic cells expressed CD3 (14/14), CD4 (14/14), PD1 (14/14), ICOS (14/14), CD10 (9/14), bcl-6 (12/14), CXCL13 (10/14), and CD30 (10/14). The HRS-like cells in five cases expressed CD20 (2/5), PAX5 (5/5), CD30 (5/5), CD15 (2/5), LCA (0/5), OCT2 (5/5) and BOB1 (2/5). Moreover, neoplastic T cells formed rosettes around HRS-like cells. EBV-encoded RNA (EBER) in situ hybridization showed scattered, small, positive bystander B lymphocytes in 8/14 cases, including 3/5 cases containing HRS-like cells. All tested cases (including five with HRS-like cells) showed monoclonal TCR gene rearrangement and polyclonal Ig gene rearrangement. Conclusions: PTGC-like FTCL is a rare tumor originated from T-follicular helper cells. It could be distinguished from angioimmunoblastic T-cell lymphoma by the formation of follicular structure, and lack of follicular dendritic cell proliferation outside the follicles and the polymorphous inflammatory background. In addition, it should be differentiated from lymphocyte-rich classical Hodgkin's lymphoma and low-grade B cell lymphoma.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Linfoma de Células T Periférico/patologia , Células de Reed-Sternberg/patologia , Infecções por Vírus Epstein-Barr , Hiperplasia/patologia , Estudos Retrospectivos , Herpesvirus Humano 4/genética , Linfadenopatia Imunoblástica/patologia , Doença de Hodgkin/patologia , Centro Germinativo/patologia , Receptores de Antígenos de Linfócitos TRESUMO
Objective: To investigate the clinical, pathological and immunophenotypic features, molecular biology and prognosis of fibrin-associated large B-cell lymphoma (LBCL-FA) in various sites. Methods: Six cases of LBCL-FA diagnosed from April 2016 to November 2021 at the Beijing Friendship Hospital, Capital Medical University, Beijing, China and the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China were collected. The cases were divided into atrial myxoma and cyst-related groups. Clinical characteristics, pathological morphology, immunophenotype, Epstein Barr virus infection status, B-cell gene rearrangement and fluorescence in situ hybridization of MYC, bcl-2, bcl-6 were summarized. Results: The patients' mean age was 60 years. All of them were male. Three cases occurred in atrial myxoma background, while the others were in cyst-related background, including adrenal gland, abdominal cavity and subdura. All cases showed tumor cells located in pink fibrin clot. However, three cyst-related cases showed the cyst wall with obviously fibrosis and inflammatory cells. All cases tested were non germinal center B cell origin, positive for PD-L1, EBER and EBNA2, and were negative for MYC, bcl-2 and bcl-6 rearrangements, except one case with MYC, bcl-2 and bcl-6 amplification. All of the 5 cases showed monoclonal rearrangement of the Ig gene using PCR based analysis. The patients had detailed follow-ups of 9-120 months, were treated surgically without radiotherapy or chemotherapy, and had long-term disease-free survivals. Conclusions: LBCL-FA is a group of rare diseases occurring in various sites, with predilection in the context of atrial myxoma and cyst-related lesions. Cyst-related lesions with obvious chronic inflammatory background show more scarcity of lymphoid cells and obvious degeneration, which are easy to be missed or misdiagnosed. LBCL-FA overall has a good prognosis with the potential for cure by surgery alone and postoperative chemotherapy may not be necessary.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Fibrilação Atrial , Infecções por Vírus Epstein-Barr , Fibrina/genética , Herpesvirus Humano 4/genética , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/patologia , Mixoma , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genéticaRESUMO
BACKGROUND: Decompressive craniectomy (DC) and intracranial pressure (ICP) monitoring are common approaches to reduce the death rate of Traumatic brain injury (TBI) patients, but the outcomes of these patients are unfavorable, particularly those who receive bilateral DC. The authors discuss their experience using ICP and other potential methods to improve the outcomes of TBI patients who receive bilateral DC. METHODS: Data from TBI patients receiving bilateral DC from Jan. 2008 to Jan. 2022 were collected via a retrospective chart review. Included patients who received unplanned contralateral DC after initial surgery were identified as unplanned secondary surgery (USS) patients. Patients' demographics and baseline medical status; pre-, intra-, and postoperative events; and follow-up visit outcome data were analyzed. RESULTS: A total of 151 TBI patients were included. Patients who underwent USS experienced more severe outcomes as assessed using the 3-month modified Rankin Scale score (P = 0.024). In bilateral DC TBI patients, USS were associated with worsen outcomes, moreover, ICP monitoring was able to lower their death rate and was associated with a lower USS incidence. In USS patients, ICP monitoring was not associated with improved outcomes but was able to lower their mortality rate (2/19, 10.5%, vs. 10/25, 40.0%; P = 0.042). CONCLUSION: The avoidance of USS may be associated with improved outcomes of TBI patients who underwent bilateral DC. ICP monitoring was a potential approach to lower USS rate in TBI patients, but its specific benefits were uncertain.
Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Craniectomia Descompressiva , Humanos , Craniectomia Descompressiva/métodos , Pressão Intracraniana , Estudos Retrospectivos , Resultado do Tratamento , Lesões Encefálicas Traumáticas/cirurgiaRESUMO
OBJECTIVE: Blood pressure variability (BPV) has been shown to correlate with poor outcomes in patients with intracerebral hemorrhage (ICH) and traumatic brain injury. However, this association has not been elucidated in patients with traumatic cervical spinal cord injury (cSCI). We hypothesized that 24-hour BPV from time of admission is associated with worse outcomes in patients with cSCI. METHODS: We performed a retrospective chart review analysis of adult patients at Huashan Hospital Fudan University between January 2006 and September 2022. We included isolated patients with traumatic cSCI within 6 hours of injury. Outcomes of patients with cSCI were assessed using 6-month American Spinal Injury Association (ASIA) impairment scale grade, and were dichotomized into poor (ASIA grade A-C, or decreasing ASIA grade compared with baseline) and good (ASIA grade D and E, or increasing ASIA grade compared with baseline) outcome groups. Blood pressures (BPs) were recorded during the first 24 hours of hospital course. BP was analyzed in the hyperacute period, from 0 to 4-5 hours; and in the acute period, from 4-5 to 24-25 hours after admission. BPV was analyzed by standard deviation (SD), coefficient of variation (CV), and successive variation (SV) of systolic BP (SBP). RESULTS: We analyzed 105 patients' charts. The first BP assessment, on emergency department arrival, at median 267 minutes (interquartile range, 152-312 minutes) after onset of injury was mean 152.2 mm Hg (SD, 51.8 mm Hg). The second BP assessment, on neurosurgical intensive care unit arrival, was mean 148.1 mm Hg (53.2 mm Hg). Poor outcomes occurred in 63 patients (60%). In univariate analysis, univariate quintile analysis or multivariate analysis, SBPSD, SBPCV, and SBPSV were associated with poor outcomes in both the hyperacute and the acute period. CONCLUSIONS: BPV during the first 24 hours after injury in patients with traumatic cSCI was independently associated with poor functional outcome at 3 months. Stabilization of BPV during the hyperacute and acute period may be a therapeutic target to improve functional outcomes of these patients.