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BACKGROUND: Preeclampsia is one of the leading causes of maternal and perinatal morbidity and is characterized by hypertension, inflammation, and placental dysfunction. Gut microbiota plays key roles in inflammation and hypertension. However, its roles and mechanisms in preeclampsia have not been fully elucidated. METHODS: 16S rRNA gene sequencing and targeted metabolomics were conducted on stool samples from 92 preeclamptic patients and 86 normal late-pregnant women. Then, fecal microbiota transplantation and in vitro and in vivo functional experiments were performed to explore the roles and mechanisms of gut microbiota in preeclampsia development. RESULTS: We revealed the gut microbiota dysbiosis in preeclamptic patients, including significant reductions in short-chain fatty acid-producing bacteria and short-chain fatty acids. The gut microbiota of preeclamptic patients significantly exacerbated pathologies and symptoms of preeclamptic rats, whereas the gut microbiota of healthy pregnant women had significant protective effects. Akkermansia muciniphila, propionate, or butyrate significantly alleviated the symptoms of preeclamptic rats. Mechanistically, they significantly promoted autophagy and M2 polarization of macrophages in placental bed, thereby suppressing inflammation. Propionate also significantly promoted trophoblast invasion, thereby improved spiral arterial remodeling. Additionally, we identified a marker set consisting of Akkermansia, Oscillibacter, and short-chain fatty acids that could accurately diagnose preeclampsia. CONCLUSIONS: Our study revealed that gut microbiota dysbiosis is an important etiology of preeclampsia. Gut microbiota and their active metabolites have great potential for the treatment and diagnosis of preeclampsia. Our findings enrich the gut-placenta axis theory and contribute to the development of microecological products for preeclampsia.
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Hipertensión , Preeclampsia , Animales , Disbiosis/microbiología , Ácidos Grasos Volátiles/metabolismo , Femenino , Humanos , Inflamación/complicaciones , Macrófagos/metabolismo , Placenta/metabolismo , Embarazo , Propionatos , ARN Ribosómico 16S/genética , Ratas , Trofoblastos/metabolismoRESUMEN
Mitochondrial dysfunction contributes to cerebral ischemia-reperfusion (CI/R) injury, which can be ameliorated by Sirtuin-3 (SIRT3). Under stress conditions, the SIRT3-promoted mitochondrial functional recovery depends on both its activity and expression. However, the approach to enhance SIRT3 activity after CI/R injury remains unelucidated. In this study, Sprague-Dawley (SD) rats were intracranially injected with either adeno-associated viral Sirtuin-1 (AAV-SIRT1) or AAV-sh_SIRT1 before undergoing transient middle cerebral artery occlusion (tMCAO). Primary cortical neurons were cultured and transfected with lentiviral SIRT1 (LV-SIRT1) and LV-sh_SIRT1 respectively before oxygen-glucose deprivation/reoxygenation (OGD/R). Afterwards, rats and neurons were respectively treated with a selective SIRT3 inhibitor, 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP). The expression, function, and related mechanism of SIRT1 were investigated by Western Blot, flow cytometry, immunofluorescence staining, etc. After CI/R injury, SIRT1 expression decreased in vivo and in vitro. The simulation and immune-analyses reported strong interaction between SIRT1 and SIRT3 in the cerebral mitochondria before and after CI/R. SIRT1 overexpression enhanced SIRT3 activity by increasing the deacetylation of SIRT3, which ameliorated CI/R-induced cerebral infarction, neuronal apoptosis, oxidative stress, neurological and motor dysfunction, and mitochondrial respiratory chain dysfunction, promoted mitochondrial biogenesis, and retained mitochondrial integrity and mitochondrial morphology. Meanwhile, SIRT1 overexpression alleviated OGD/R-induced neuronal death and mitochondrial bioenergetic deficits. These effects were reversed by AAV-sh_SIRT1 and the neuroprotective effects of SIRT1 were partially offset by 3-TYP. These results suggest that SIRT1 restores the structure and function of mitochondria by activating SIRT3, offering neuroprotection against CI/R injury, which signifies a potential approach for the clinical management of cerebral ischemia.
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Isquemia Encefálica , Mitocondrias , Neuronas , Daño por Reperfusión , Sirtuina 1 , Sirtuina 3 , Animales , Masculino , Ratas , Apoptosis , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Mitocondrias/metabolismo , Neuronas/metabolismo , Neuronas/patología , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Sirtuina 1/metabolismo , Sirtuina 1/genética , Sirtuina 3/metabolismo , Sirtuina 3/genética , SirtuinasRESUMEN
Microglia, the resident immune cells of the central nervous system (CNS), play a dual role in neurotoxicity by releasing the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF) in response to environmental stress. Suppression of BDNF is implicated in learning and memory impairment induced by exposure to manganese (Mn) or lead (Pb) individually. Methyl CpG Binding Protein 2 (MeCp2) and its phosphorylation status are related to BDNF suppression. Protein phosphatase2A (PP2A), a member of the serine/threonine phosphatases family, dephosphorylates substrates based on the methylation state of its catalytic C subunit (PP2Ac). However, the specific impairment patterns and molecular mechanisms resulting from co-exposure to Mn and Pb remain unclear. Therefore, the purpose of this study was to explore the effects of Mn and Pb exposure, alone and in combination, on inducing neurotoxicity in the hippocampus of mice and BV2 cells, and to determine whether simultaneous exposure to both metals exacerbate their toxicity. Our findings reveal that co-exposure to Mn and Pb leads to severe learning and memory impairment in mice, which correlates with the accumulation of metals in the hippocampus and synergistic suppression of BDNF. This suppression is accompanied by up-regulation of the epigenetic repressor MeCp2 and its phosphorylation status, as well as demethylation of PP2Ac. Furthermore, inhibition of PP2Ac demethylation using ABL127, an inhibitor for its protein phosphatase methylesterase1 (PME1), or knockdown of MeCp2 via siRNA transfection in vitro effectively increases BDNF expression and mitigates BV2 cell damage induced by Mn and Pb co-exposure. We also observe abnormal activation of microglia characterized by enhanced release of the NLRP3 inflammasome, Casepase-1 and pro-inflammatory cytokines IL-1ß, in the hippocampus of mice and BV2 cells. In summary, our experiments demonstrate that simultaneous exposure to Mn and Pb results in more severe hippocampus-dependent learning and memory impairment, which is attributed to epigenetic suppression of BDNF mediated by PP2A regulation.
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Factor Neurotrófico Derivado del Encéfalo , Epigénesis Genética , Hipocampo , Plomo , Manganeso , Trastornos de la Memoria , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ratones , Epigénesis Genética/efectos de los fármacos , Manganeso/toxicidad , Plomo/toxicidad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Trastornos de la Memoria/inducido químicamente , Masculino , Ratones Endogámicos C57BL , Microglía/efectos de los fármacos , Proteína 2 de Unión a Metil-CpG/metabolismo , Proteína 2 de Unión a Metil-CpG/genética , Proteína Fosfatasa 2/metabolismo , Aprendizaje/efectos de los fármacosRESUMEN
BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).
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Betacoronavirus , Infecciones por Coronavirus , Brotes de Enfermedades , Pandemias , Neumonía Viral , Adolescente , Adulto , Anciano , COVID-19 , Niño , China/epidemiología , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Femenino , Fiebre/etiología , Humanos , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/terapia , SARS-CoV-2 , Adulto JovenRESUMEN
BACKGROUND: Oxaliplatin resistance is a complex process and has been one of the most disadvantageous factors and indeed a confrontation in the procedure of colorectal cancer. Recently, long non-coding RNAs (lncRNAs) have emerged as novel molecules for the treatment of chemoresistance, but the specific molecular mechanisms mediated by them are poorly understood. METHODS: The lncRNAs associated with oxaliplatin resistance were screened by microarray. lncRNA effects on oxaliplatin chemoresistance were then verified by gain- and loss-of-function experiments. Finally, the potential mechanism of AC092894.1 was explored by RNA pull-down, RIP, and Co-IP experiments. RESULTS: AC092894.1 representation has been demonstrated to be drastically downregulated throughout oxaliplatin-induced drug-resistant CRC cells. In vivo and in vitro experiments revealed that AC092894.1 functions to reverse chemoresistance. Studies on the mechanism suggested that AC092894.1 served as a scaffold molecule that mediated the de-ubiquitination of AR through USP3, thereby increasing the transcription of RASGRP3. Finally, sustained activation of the MAPK signaling pathway induced apoptosis in CRC cells. CONCLUSIONS: In conclusion, this study identified AC092894.1 as a suppressor of CRC chemoresistance and revealed the idea that targeting the AC092894.1/USP3/AR/RASGRP3 signaling axis is a novel option for the treatment of oxaliplatin resistance.
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Neoplasias Colorrectales , MicroARNs , ARN Largo no Codificante , Humanos , Oxaliplatino/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Regulación hacia Abajo , ARN Largo no Codificante/genética , MicroARNs/metabolismo , Resistencia a Antineoplásicos/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proteasas Ubiquitina-Específicas/genética , Proteasas Ubiquitina-Específicas/metabolismoRESUMEN
BACKGROUND: Long non-coding RNAs (lncRNAs) have been confirmed to play important roles in various cancers including bladder cancer (BC). The precise expression pattern of lncRNA small nucleolar RNA host gene 18 (SNHG18) in BC and its mechanisms of action have not been fully explored. MATERIALS AND METHODS: The expression of SNHG18 was evaluated by RT-qPCR in bladder cancer clinical samples and human bladder cancer cell lines, and stable cell lines overexpressing SNHG18 were constructed. The effect of SNHG18 on the proliferation of bladder cancer cells was detected by soft agar colony formation test, ATP activity test and subcutaneous tumorigenesis model in nude mice. The specific mechanism of SNHG18 inhibition of bladder cancer proliferation was studied by flow cytometry, western blotting, dual luciferase reporter gene assay and protein degradation assay. RESULTS: We found that SNHG18 is significantly downregulated in BC tissues and cell lines. Kaplan-Meier analysis showed that SNHG18 expression is positively correlated with survival in BC patients. Ectopic overexpression of SNHG18 significantly inhibited the proliferation of BC cells in vitro and in vivo. Further mechanistic investigations demonstrated that SNHG18 inhibited c-Myc expression by modulating the ubiquitination-proteasome pathway and that c-Myc is the critical transcription factor that mediates SNHG18 inhibition of BC growth by directly binding to the p21 promoter, which was attributed with significant p21 accumulation. CONCLUSIONS: SNHG18 promotes the transcription and expression of p21 by inhibiting c-Myc expression, leading to G0-G1 arrest and inhibiting the proliferation of bladder cancer cells. These findings highlight a novel cell cycle regulatory mechanism involving the SNHG18/c-Myc/p21 pathway in BC pathogenesis and could potentially lead to new lncRNA-based diagnostics and/or therapeutics for BC.
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BACKGROUND: Circular RNAs (circRNAs) are a class of noncoding RNAs that are involved in the progression of many human cancers. The precise gene locus and the roles of circular RNA from Fibronectin type III domain containing 3B (FNDC3B) in OS and its mechanisms of action have not been fully explored. MATERIALS AND METHODS: qRT-qPCR assay was used to determine gene expressions. CCK8 Assay, EdU assay, wound-healing assay, transwell invasion assay and in vivo xenograft assay were used to perform functional investigations. RNA-FISH, immunofluorescence, RIP assay, RNA stability analysis were applied in mechanistic studies. RESULTS: We found that circFNDC3B downregulated and FNDC3B mRNA upregulated in OS, and might be potential biomarkers for indicating disease progression and prognosis of OS patients. CircFNDC3B acted as a tumor suppressor gene to restrain OS progression and FNDC3B functioned as an oncogene to promote OS progression in vitro and in vivo. RNA binding protein RNA binding motif protein 47 (RBM47) could bind to the flanking introns of circFNDC3B to facilitate the generation of circFNDC3B, resulting in the reduction of FNDC3B mRNA and the circFNDC3B-FNDC3B mRNA imbalance. CircFNDC3B also inhibited FNDC3B mRNA expression by reducing its stability via competitively binding to Insulin-like growth-factor-2 mRNA binding protein (IGF2BP1). CONCLUSION: This study demonstrated that RBM47 and IGF2BP1 mediated circular FNDC3B/FNDC3B mRNA imbalance was involved in the malignant processes of OS.
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A binuclear Ni(II)-based metal-organic framework {[Ni2(btb)1.333(H2O)3.578(py)1.422]·(DMF)(H2O)3.25}n (Nibtb) was solvothermally synthesized (H3btb = 1,3,5-tri(4-carboxylphenyl)benzene, py = pyridine, DMF = N,N-dimethylformamide). Nibtb shows a rare 2-fold interpenetrating (3,4)-connected 3D network with a point symbol of (83)4(86)3 based on binuclear Ni(II) clusters. Nibtb as a heterogeneous catalyst combines the high stability of MOFs and excellent catalytic activity of nickel, which exhibits excellent catalytic activity for the synthesis of benzimidazoles and pyrazoles under mild conditions. Moreover, the catalyst can be easily separated and reused for seven successive cycles and maintains high catalytic activity.
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BACKGROUND: There is no clear consensus on the benefits of adjuvant chemotherapy for tumor-node-metastasis (TNM) stage T1 (T1N0M0) breast cancer (BC). Our study investigated the effects of adjuvant chemotherapy on T1N0M0 BC patients. METHODS: Seventy-five thousand one hundred thirty-nine patients diagnosed with T1N0M0 BC were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox analyses were performed to investigate the effects of adjuvant chemotherapy on T1a, T1b, and T1cN0M0 BC, including various tumor grades, and four molecular subtypes. Propensity score matching (PSM) was used to eliminate confounding factors and further compare the results between adjuvant chemotherapy and no adjuvant chemotherapy. Additionally, 545 T1N0M0 BC patients treated at the Northern Jiangsu People's Hospital were included as an independent external validation cohort. Univariate and multivariate Cox analyses were used to confirm the effects of adjuvant chemotherapy in T1a, T1b, and T1cN0M0 BC. Survival curves for the different tumor grades and molecular subtypes were plotted using the Kaplan-Meier method. RESULTS: Adjuvant chemotherapy demonstrated a statistically significant improvement in overall survival (OS) in T1b and T1c BC, but not in T1a BC. Within T1b BC, adjuvant chemotherapy was found to have effects on grade III, and hormone receptor + (HoR +)/human epidermal growth factor receptor 2 + (HER2 +), HoR-/HER2 + , and HoR-/HER2- molecular subtypes, respectively. Adjuvant chemotherapy was beneficial to OS for grade II/III and T1c BC. Identical results were obtained after PSM. We also obtained similar results with external validation cohort, except that adjuvant chemotherapy made a difference in grade II and T1b BC of the external validation dataset. CONCLUSIONS: Partial T1N0M0 BC patients with grade III T1bN0M0, patients with tumor grade II and III T1cN0M0, and excluding those with HoR + /HER2- subtype tumors, could obtain OS benefits from adjuvant chemotherapy.
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Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Quimioterapia Adyuvante/métodos , Estudios de Cohortes , Femenino , Humanos , Estadificación de Neoplasias , Pronóstico , Puntaje de Propensión , Receptor ErbB-2/metabolismoRESUMEN
We report a compact, self-starting dispersion-managed mode-locked thulium-doped fiber oscillator that delivers 2.6 nJ pulses at 2 µm with a repetition rate of 250 MHz. The average output power and spectral bandwidth of the pulses reach impressive values of 648 mW and 103 nm, respectively. The generated pulses are near linearly chirped, capable of linearly compressing to 74 fs in a normal dispersion fiber after power attenuation. Using a nonlinear fiber compression scheme can even compress the pulses to 29 fs (4.3-cycle). The remaining pulse energy is 1.15 nJ, and the corresponding peak power is estimated as 39.4 kW. To the best of our knowledge, this is the first demonstration of nonlinearly compressing the pulse of a 2 µm fiber oscillator to the sub-5 cycle regime. Such a few-cycle fiber laser could be an ideal candidate source for short-wavelength mid-infrared frequency metrology and molecular spectroscopy applications.
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BACKGROUND: Crucial roles of hematologic and immunologic responses in progression of coronavirus disease 2019 (COVID-19) remain largely unclear. OBJECTIVE: We sought to address the dynamic changes in hematologic and immunologic biomarkers and their associations with severity and outcomes of COVID-19. METHODS: A retrospective study including 548 patients with COVID-19 with clarified outcome (discharged or deceased) from a national cohort in China was performed. Cross-sectional and longitudinal variations were compared and the associations with different severity and outcomes were analyzed. RESULTS: On admission, the counts of lymphocytes, T-cell subsets, eosinophils, and platelets decreased markedly, especially in severe/critical and fatal patients. Increased neutrophil count and neutrophils-to-lymphocytes ratio were predominant in severe/critical cases or nonsurvivors. During hospitalization, eosinophils, lymphocytes, and platelets showed an increasing trend in survivors, but maintained lower levels or dropped significantly afterwards in nonsurvivors. Nonsurvivors kept a high level or showed an upward trend for neutrophils, IL-6, procalcitonin, D-dimer, amyloid A protein, and C-reactive protein, which were kept stable or showed a downward trend in survivors. Positive correlation between CD8+ T-cell and lymphocytes count was found in survivors but not in nonsurvivors. A multivariate Cox regression model suggested that restored levels of lymphocytes, eosinophils, and platelets could serve as predictors for recovery, whereas progressive increases in neutrophils, basophils, and IL-6 were associated with fatal outcome. CONCLUSIONS: Hematologic and immunologic impairment showed a significantly different profile between survivors and nonsurvivors in patients with COVID-19 with different severity. The longitudinal variations in these biomarkers could serve to predict recovery or fatal outcome.
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Biomarcadores/sangre , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/inmunología , Neumonía Viral/sangre , Neumonía Viral/inmunología , Adulto , Anciano , Betacoronavirus , COVID-19 , China , Estudios de Cohortes , Infecciones por Coronavirus/mortalidad , Estudios Transversales , Progresión de la Enfermedad , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/mortalidad , Pronóstico , Estudios Retrospectivos , SARS-CoV-2RESUMEN
BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. OBJECTIVE: To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. METHODS: We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities. RESULTS: The mean age was 48.9â years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424-5.048)), diabetes (1.59 (1.03-2.45)), hypertension (1.58 (1.07-2.32)) and malignancy (3.50 (1.60-7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16-2.77) among patients with at least one comorbidity and 2.59 (1.61-4.17) among patients with two or more comorbidities. CONCLUSION: Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.
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Betacoronavirus , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Adulto , COVID-19 , China/epidemiología , Comorbilidad , Infecciones por Coronavirus/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico , Pronóstico , Factores de Riesgo , SARS-CoV-2RESUMEN
BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9â years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5â days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7â days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.
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Infecciones por Coronavirus/mortalidad , Hospitalización , Neumonía Viral/mortalidad , Adulto , Anciano , Betacoronavirus , COVID-19 , Enfermedades Cardiovasculares/epidemiología , China , Estudios de Cohortes , Comorbilidad , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico por imagen , Tos/etiología , Diabetes Mellitus/epidemiología , Brotes de Enfermedades , Disnea/etiología , Fatiga/etiología , Femenino , Fiebre/etiología , Geografía , Humanos , Hipertensión/epidemiología , Unidades de Cuidados Intensivos/estadística & datos numéricos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Pandemias , Faringitis/etiología , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico por imagen , Pronóstico , Modelos de Riesgos Proporcionales , Respiración Artificial/estadística & datos numéricos , Estudios Retrospectivos , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factores de Tiempo , Tiempo de Tratamiento/estadística & datos numéricos , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND AND AIM: Nowadays, anti-inflammation treatment is a promising approach for preventing tumorigenesis, and human microflora is closely related to inflammation. This study aimed to investigate the gastric cardiac microbiome and identify inflammation-related microorganisms for gastric cardiac inflammation. METHODS: We performed 16S rRNA sequencing on a total of 11 healthy individuals and 89 individuals with different degree of gastric cardiac inflammation. Immunohistochemistry was used for verifying candidate bacteria. Phylogenetic reconstruction of unobserved states (picrust) was used for predicting the pathways involved by cardiac microflora. RESULTS: The resident phyla in normal were Proteobacteria, Firmicutes, Bacteroides, and Actinobacteria, and the dominant genus in normal were Halomonas, shewanella, and Comamonas. In the progression of gastric cardiac inflammation, the diversity of cardiac microflora did not change (P > 0.05). However, the composition structure of cardiac microflora varied between healthy and inflamed tissues (P < 0.05). Meanwhile, there were 64 species parallel increased with inflammation degree, especially Helicobacter pylori, Lactobacillus spp. Additionally, inflammation-related species were detected (P < 0.05), including H. pylori, Acinetobacter ursingii, and Streptococcus agalactiae. Higher H. pylori colonization was positively related to the progression of cardiac inflammation (γ coefficient = 0.678, P < 0.001), and it also influenced the cardiac microbial community structure. Cardiac microflora also participated in DNA repair pathways and is affected by the relative abundance of H. pylori (P < 0.0001). CONCLUSIONS: Cardiac microflora dysbiosis, especially the increasing of the relevant abundance of H. pylori, promotes the progression of cardiac inflammation.
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Cardias/microbiología , Disbiosis , Inflamación/etiología , Inflamación/microbiología , Microbiota , Acinetobacter , Adulto , Anciano , Anciano de 80 o más Años , Reparación del ADN , Femenino , Helicobacter pylori , Humanos , Lactobacillus , Masculino , Persona de Mediana EdadRESUMEN
A passively mode-locked thulium-doped fiber laser using a tungsten ditelluride saturable absorber (${{\rm WTe}_2}\mbox{-}{\rm SA}$WTe2-SA) is demonstrated. High-power mode-locked pulses with an average output power of 108.1 mW were achieved by incorporating the ${{\rm WTe}_2}\mbox{-}{\rm SA}$WTe2-SA into a thulium-doped fiber oscillator. To the best of our knowledge, this is the highest average power obtained from a ${{\rm WTe}_2}\mbox{-}{\rm SA}$WTe2-SA-based fiber laser. We further amplified the output power to 5.60 W with an all-fiber thulium-doped double-cladding fiber amplifier. Our result indicates that ${{\rm WTe}_2}\mbox{-}{\rm SA}$WTe2-SA could be an excellent candidate for a high-power fiber laser system.
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Herein, we present a fundamental and harmonic mode-locked figure-of-9 thulium-doped fiber laser using a nonlinear amplifying loop mirror. The generated fundamental mode-locked h-shaped pulse is centered at 1889â nm with an average output power reaching 282â mW and a pulse energy up to 1.23 µJ, which is the highest power and pulse energy of an h-shaped pulse. In the harmonic mode-locked regime, up to the 8th harmonic h-shaped pulse is obtained. The detailed characteristics of the h-shaped pulse are discussed. The proposed study shows that the figure-of-9 fiber laser can generate h-shaped pulses and also allows the generation of nanosecond pulses with a µJ-level pulse energy.
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In this paper, we first achieve nanosecond-scale dissipative soliton resonance (DSR) generation in a thulium-doped double-clad fiber (TDF) laser with all-anomalous-dispersion regime, and also first scale the average power up to 100.4 W by employing only two stage TDF amplifiers, corresponding to gains of 19.3 and 14.4 dB, respectively. It is noted that both the fiber laser oscillator and the amplification system employ double-clad fiber as the gain medium for utilizing the advantages in high-gain-availability, high-power-handling and good-mode-quality-maintaining. DSR mode-locking of the TDF oscillator is realized by using a nonlinear optical loop mirror (NOLM), which exhibits all-fiber-format, high nonlinear and passive saturable absorption properties. The TDF oscillator can deliver rectangular-shape pulses with duration ranging from ~3.74 to ~72.19 ns while maintaining a nearly equal output peak power level of ~0.56 W, namely peak power clamping (PPC) effect. Comparatively, the two stage amplifiers can scale the seeding pulses to similar average power levels, but to dramatically different peak powers ranging from ~0.94 to ~18.1 kW depending on the durations. Our TDF master-oscillator-power-amplifier (MOPA) system can provide a high power 2-µm band all-fiber-format laser source both tunable in pulse duration and peak power.
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PURPOSE: Minimally invasive gastrectomy for gastric carcinoma is gaining widespread acceptance. However, data are still lacking on the feasibility, long- and short-term outcomes of laparoscopic total gastrectomy. The purpose of the study was to evaluate the feasibility, safety and long-term results of laparoscopic total gastrectomy. METHODS: Between January 2008 and January 2013, 74 patients with gastric carcinoma who had been subjected to laparoscopic total gastrectomy were evaluated. Each patient was matched to one patient undergoing open total gastrectomy for age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) grade and clinical TNM stage. Surgical and long-term survival outcomes were evaluated. RESULTS: No differences in baseline data, pathological data and incidence of postoperative 30-day complications were found between the two groups. The blood loss and postoperative hospital stay for the laparoscopy group was significantly shorter than for the open group. In long-term results, no difference was found in overall survival rate (p=0.257) and disease-free survival rate (=0.207) between the two groups. When patients were analyzed according to the pathological TNM stage, the 5-year overall survival rates and disease-free survival rates were not different. CONCLUSION: Laparoscopic total gastrectomy for gastric carcinoma is feasible and results in comparable oncologic outcomes as in open total gastrectomy.
Asunto(s)
Gastrectomía/métodos , Laparoscopía/métodos , Neoplasias Gástricas/cirugía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/mortalidadRESUMEN
Adipose-derived stem cell, one type of mesenchymal stem cells, is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery. However, its application has been limited by the complexities of the ischemic microenvironment. Hydrogel scaffolds, which are composed of hyaluronic acid and chitosan, exhibit excellent biocompatibility and biodegradability, making them promising candidates as cell carriers. Vascular endothelial growth factor is a crucial regulatory factor for stem cells. Both hyaluronic acid and chitosan have the potential to make the microenvironment more hospitable to transplanted stem cells, thereby enhancing the therapeutic effect of mesenchymal stem cell transplantation in the context of stroke. Here, we found that vascular endothelial growth factor significantly improved the activity and paracrine function of adipose-derived stem cells. Subsequently, we developed a chitosan-hyaluronic acid hydrogel scaffold that incorporated vascular endothelial growth factor and first injected the scaffold into an animal model of cerebral ischemia-reperfusion injury. When loaded with adipose-derived stem cells, this vascular endothelial growth factor-loaded scaffold markedly reduced neuronal apoptosis caused by oxygen-glucose deprivation/reoxygenation and substantially restored mitochondrial membrane potential and axon morphology. Further in vivo experiments revealed that this vascular endothelial growth factor-loaded hydrogel scaffold facilitated the transplantation of adipose-derived stem cells, leading to a reduction in infarct volume and neuronal apoptosis in a rat model of stroke induced by transient middle cerebral artery occlusion. It also helped maintain mitochondrial integrity and axonal morphology, greatly improving rat motor function and angiogenesis. Therefore, utilizing a hydrogel scaffold loaded with vascular endothelial growth factor as a stem cell delivery system can mitigate the adverse effects of ischemic microenvironment on transplanted stem cells and enhance the therapeutic effect of stem cells in the context of stroke.
RESUMEN
Background/purpose: Secretory carcinoma (SC) is a rare salivary gland tumor that featured by ETV6::NTRK3 gene fusion, and was included in the WHO Classification of Head and Neck Tumors since 2017. Nevertheless, the description of SCs by WHO is still vague. This study examined 18 SC cases by using both histomorphology and molecular pathology for diagnostic determination, especially immunohistochemical features of SCs. Materials and methods: Based on WHO characteristics, 18 patients with SC admitted between 2001 and 2022 were included in this study. Main histomorphological patterns, FISH analyses of the ETV6::NTRK3 gene fusion, and immunohistochemical analyses of S100, mammaglobin, DOG1, ADFP, CA6 and Ki-67 were performed. Results: Among the 18 SC patients, the median age of onset was 39.22 years. Grossly, the average tumor size in 2.96 cm with various texture from soft to tough. The majority patients were positive for S100, mammaglobin, and negative for DOG1, except for one patient negative for S100 (Case 18). All patients were positive for ADFP, and the majority patients were negative for CA6, except for Case 9. Two cases were found recurrence, and the tumor were found both in parotid gland with local invasion. Conclusion: Combined with the results of previous studies, we proposed that the combination of all five markers, S100, mammaglobin, DOG1, ADFP and CA6, could contribute more to differential diagnosis of SCs with other salivary carcinomas, especially with AciCC. The prognosis of SCs is optimistic in most cases, but larger patient cohort and long-term follow-up are still needed.