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Esophageal adenocarcinoma (EAC) is one of the most malignant tumors in the digestive system. To make thing worse, the scarcity of treatment options is disheartening. However, if detected early, there is a possibility of reversing the condition. Unfortunately, there is still a lack of relevant early screening methods. Considering that Barrett's esophagus (BE), a precursor lesion of EAC, has been confirmed as the only known precursor of EAC. Analyzing which BE cases will progress to EAC and understanding the processes and mechanisms involved is of great significance for early screening of such patients. Considering the significant alterations in the gut microbiota of patients with BE and its potential role in the progression to EAC, this study aims to analyze the relationship between BE, EAC, and GM to identify potential diagnostic biomarkers and therapeutic targets. This study utilized comprehensive statistical data on gut microbiota from a large-scale genome-wide association meta-analysis conducted by the MiBioGen consortium (n = 18,340). Subsequently, we selected a set of single nucleotide polymorphisms (SNPs) that fell below the genome-wide significance threshold (1 × 10-5) as instrumental variables. To investigate the causal relationship between gut microbiota and BE and EAC, we employed various MR analysis methods, including Inverse Variance Weighting (IVW), MR-Egger regression, weighted median (WM), and weighted mean. Additionally, we assessed the level of pleiotropy, heterogeneity, and stability of genetic variations through MR-Egger intercept test, MR-PRESSO, Cochran's Q test, and "leave-one-out" sensitivity analysis. Furthermore, we conducted reverse MR analysis to identify the causal relationships between gut microbiota and BE and EAC. The results from the Inverse Variance-Weighted (IVW) analysis indicate that Alistipes (P = 4.86 × 10-2), Lactobacillus (P = 2.11 × 10-2), Prevotella 7 (P = 4.28 × 10-2), and RuminococcaceaeUCG004 (P = 4.34 × 10-2) are risk factors for Barrett's esophagus (BE), while Flavonifractor (P = 8.81 × 10-3) and RuminococcaceaeUCG004 (P = 4.99 × 10-2) are risk factors for esophageal adenocarcinoma (EAC). On the other hand, certain gut microbiota genera appear to have a protective effect against both BE and EAC. These include Eubacterium (nodatum group) (P = 4.51 × 10-2), Holdemania (P = 1.22 × 10-2), and Lactococcus (P = 3.39 × 10-2) in the BE cohort, as well as Eubacterium (hallii group) (P = 4.07 × 10-2) and Actinomyces (P = 3.62 × 10-3) in the EAC cohort. According to the results of reverse MR analysis, no significant causal effects of BE and EAC on gut microbiota were observed. Furthermore, no significant heterogeneity or pleiotropy was detected in the instrumental variables. We have established a causal relationship between the gut microbiota and BE and EAC. This study holds profound significance for screening BE patients who may be at risk of deterioration, as it can provide them with timely medical interventions to reverse the condition.
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Adenocarcinoma , Esófago de Barrett , Neoplasias Esofágicas , Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Esófago de Barrett/genética , Esófago de Barrett/microbiología , Esófago de Barrett/patología , Microbioma Gastrointestinal/genética , Humanos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/microbiología , Neoplasias Esofágicas/patología , Adenocarcinoma/genética , Adenocarcinoma/microbiología , Adenocarcinoma/patologíaRESUMEN
The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of mono antibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement. Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Receptores de N-Metil-D-Aspartato , Humanos , Masculino , Adulto Joven , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Autoanticuerpos , Glicoproteína Mielina-Oligodendrócito , Convulsiones/complicaciones , SíndromeRESUMEN
OBJECTIVES: To explore the added value of arterial enhancement fraction (AEF) derived from dual-energy computed tomography CT (DECT) to conventional image features for diagnosing cervical lymph node (LN) metastasis in papillary thyroid cancer (PTC). METHODS: A total of 273 cervical LNs (153 non-metastatic and 120 metastatic) were recruited from 92 patients with PTC. Qualitative image features of LNs were assessed. Both single-energy CT (SECT)-derived AEF (AEFS) and DECT-derived AEF (AEFD) were calculated. Correlation between AEFD and AEFS was determined using Pearson's correlation coefficient. Multivariate logistic regression analysis with the forward variable selection method was used to build three models (conventional features, conventional features + AEFS, and conventional features + AEFD). Diagnostic performances were evaluated using receiver operating characteristic (ROC) curve analyses. RESULTS: Abnormal enhancement, calcification, and cystic change were chosen to build model 1 and the model provided moderate diagnostic performance with an area under the ROC curve (AUC) of 0.675. Metastatic LNs demonstrated both significantly higher AEFD (1.14 vs 0.48; p < 0.001) and AEFS (1.08 vs 0.38; p < 0.001) than non-metastatic LNs. AEFD correlated well with AEFS (r = 0.802; p < 0.001), and exhibited comparable performance with AEFS (AUC, 0.867 vs 0.852; p = 0.628). Combining CT image features with AEFS (model 2) and AEFD (model 3) could significantly improve diagnostic performances (AUC, 0.865 vs 0.675; AUC, 0.883 vs 0.675; both p < 0.001). CONCLUSIONS: AEFD correlated well with AEFS, and exhibited comparable performance with AEFS. Integrating qualitative CT image features with both AEFS and AEFD could further improve the ability in diagnosing cervical LN metastasis in PTC. CLINICAL RELEVANCE STATEMENT: Arterial enhancement fraction (AEF) values, especially AEF derived from dual-energy computed tomography, can help to diagnose cervical lymph node metastasis in patients with papillary thyroid cancer, and complement conventional CT image features for improved clinical decision making. KEY POINTS: ⢠Metastatic cervical lymph nodes (LNs) demonstrated significantly higher arterial enhancement fraction (AEF) derived from dual-energy computed tomography (DECT) and single-energy CT (SECT)-derived AEF (AEFS) than non-metastatic LNs in patients with papillary thyroid cancer. ⢠DECT-derived AEF (AEFD) correlated significantly with AEFS, and exhibited comparable performance with AEFS. ⢠Integrating qualitative CT images features with both AEFS and AEFD could further improve the differential ability.
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Neoplasias de la Tiroides , Tomografía Computarizada por Rayos X , Humanos , Cáncer Papilar Tiroideo/patología , Metástasis Linfática/patología , Tomografía Computarizada por Rayos X/métodos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Neoplasias de la Tiroides/patología , Estudios RetrospectivosRESUMEN
Panax ginseng is a perennial herb with the main active compounds of ginsenosides. Among the reported ginsenosides, ginsenoside Rg_1 not only has a wide range of medicinal functions and abundant content but also is one of the major ginsenoside for the quality evaluation of this herb in the Chinese Pharmacopoeia. The main biosynthesis pathway of ginsenoside Rg_1 in P. ginseng has been clarified, which lays a foundation for the comprehensive and in-depth analysis of the biosynthesis and regulatory mechanism of ginseno-side Rg_1. However, the biosynthesis of ginsenoside Rg_1 is associated with other complex processes involving a variety of regulatory genes and catalyzing enzyme genes, which remain to be studied comprehensively. With the transcriptome data of 344 root samples from 4-year-old P. ginseng plants and their corresponding ginsenoside Rg_1 content obtained in the previous study, this study screened out 217 differentially expressed genes(DEGs) with Rg_1 content changes by DEseq2 analysis in R language. Furthermore, the weighted gene co-expression network analysis(WGCNA) revealed 40 hub genes among the DEGs.Pearsoncorrelation analysis was further perforned to yield 20 candidate genes significantly correlated with ginsenoside Rg_1 content, and these genes were annotated to multiple metabolic processes including primary metabolism and secondary metabolism. Finally, the treatment of P. ginseng adventitious roots with methyl jasmonate indicated that 16 of these genes promoted the biosynthesis of ginsenoside Rg_1 in response to methyl jasmonate induction. Finally, one of the 16 genes was randomly selected to verify the function of the gene by genetic transformation and qRT-PCR and to confirm the rationality of the methodology of this study. The above results lay a foundation for studying the mechanism for regulation on the synthesis of ginsenoside Rg_1 and provide genetic resources for the industrial production of ginsenoside Rg_1.
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Regulación de la Expresión Génica de las Plantas , Ginsenósidos , Panax , Ginsenósidos/biosíntesis , Panax/genética , Panax/metabolismo , Panax/química , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilación de la Expresión GénicaRESUMEN
PURPOSE: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. METHODS: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. RESULTS: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. CONCLUSION: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.
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Adenosina Desaminasa , Péptidos y Proteínas de Señalización Intercelular , Humanos , Adenosina Desaminasa/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Estudios de Cohortes , Estudios Retrospectivos , MutaciónRESUMEN
Neuronal surface antibody-mediated autoimmune encephalitis (NSAE) occurs across a wide age range. However, few studies focused on the onset age and their related characteristics. We aimed to explore the age-dependent profile of NSAE. A total of 134 patients with a definite diagnosis of NSAE were retrospectively enrolled from 3 tertiary hospitals between July 2014 and August 2020. Demographic, clinical, therapeutic, and prognostic data were collected and compared between the late- (≥45) and younger-onset (<45) groups. The results showed that 56 (41.8%) patients were classified as late-onset NSAE, and 78 (58.2%) as younger-onset NSAE. There were more males, especially in the late-onset group (P = 0.036). Prodromal symptoms were more common in the younger-onset group (P = 0.004). Among the onset symptoms, more late-onset patients presented as seizures, while more younger-onset patients presented as psychiatric symptoms. Throughout the disease course, the late-onset patients were more likely to have memory dysfunction (P < 0.001), but less likely to have central hypoventilation (P = 0.045). The late-onset patients also had a significantly lower modified Rankin Scale score on admission (P = 0.042), required intensive care unit (ICU) admission less frequently during hospitalization (P = 0.042) and had a shorter hospital stay (P = 0.014). Our study revealed that the late- and younger-onset NSAE had a distinct spectrum of demographic features, presentations, and prognoses. More attention is needed for the younger-onset patients, given a higher disease severity on admission, more frequent requirement for ICU admission and longer length of stay.
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Enfermedades Autoinmunes del Sistema Nervioso , Hospitalización , Masculino , Humanos , Estudios Retrospectivos , PronósticoRESUMEN
Twelve kinds of 8-hydroxyquinoline derivatives were synthesized and characterized. The weight loss method was used to evaluate their inhibition efficiencies (IEs) in a 1.0 M HCl solution at 333 K. The results showed that the alkyl chain length, heteroatoms (S, N, and O), and number of benzene rings significantly affect the IE. Herein, the IE of 5-[(dodecylthio)methyl]-8-quinolinol reached 98.71%. Meanwhile, the potentiodynamic polarization results indicated that all 8-hydroxyquinoline derivatives were mixed-type inhibitors. Electrochemical impedance spectroscopy results revealed that 8-hydroxyquinoline derivatives can increase polarization resistance, supporting their adsorption on the N80 steel surface. Moreover, according to density functional theory (DFT), the frontier orbital distribution and quantum chemical parameters (EHOMO, ELUMO, dipole moment µ, etc.) were calculated, and the results confirmed that the substituents of protonated 8-hydroxyquinoline derivatives significantly influenced the frontier orbital distribution. Molecular dynamics simulation illustrated that all protonated 8-hydroxyquinoline derivatives were adsorbed parallel to the Fe(110) surface, and the interaction energy (Eint) evidenced that the molecular size would affect their strength of adsorption on the Fe(110) surface. The linear and nonlinear quantitative structure-activity relationship models were established by linear regression (LR) methods and BP neural networks (NN), respectively. The LR model was established by using Eint and µ, and the coefficient of determination (R2) was 0.934. In addition, the nonlinear NN model was obtained according to IE and all parameters (DFT parameters and Eint). Then, the two calculation inhibition efficiencies (IEcal) were obtained from the LR and NN models, and the R2 values of the linear correlation between the IEcal and the experimental IE were 0.940 and 0.951, respectively. In addition, the IE of the tested inhibitor was 51.86% and the IEcal values predicted by the LR and NN models were 52.68% and 53.06%, respectively. Our results demonstrate that both the LR and NN models have good fits and predictive ability.
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PURPOSE: To study the influence of sex, age and thyroid function indices on dual-energy computed tomography (DECT)-derived quantitative parameters of thyroid in patients with or without Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: A total of 198 consecutive patients who underwent DECT scan of neck due to unilateral thyroid lesions were retrospectively enrolled. Iodine concentration (IC), total iodine content (TIC) and volume of normal thyroid lobe were calculated. Influences of sex, age and thyroid function indices on DECT-derived parameters in overall study population, subgroup patients with, and those without HT were assessed using Mann-Whitney U test, Student's T-test, and Spearman correlation analyses, respectively, as appropriate. RESULTS: HT group showed significantly lower IC and TIC, while higher volume than No-HT group (all p < 0.001). The volume was larger in male than that in female in overall study population and No-HT group (p = 0.047 and 0.010, respectively). There was no significant difference in any DECT-derived parameters between low (≤ 35 years) and high (> 35 years) age group in all three groups (all p > 0.05). TPOAb and TgAb correlated positively with IC and TIC, and negatively with volume in overall study population (all p < 0.05). TPOAb and TgAb also correlated positively with IC in HT group (p = 0.002 and 0.007, respectively). CONCLUSION: DECT-derived parameters of thyroid differed significantly between patients with and without HT. Sex and thyroid function indices could affect the DECT-derived parameters. Aforementioned physiological factors should be considered when analyzing the DECT-derived parameters of thyroid.
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Enfermedad de Hashimoto , Yodo , Humanos , Masculino , Femenino , Estudios Retrospectivos , Enfermedad de Hashimoto/diagnóstico por imagen , Enfermedad de Hashimoto/patología , TomografíaRESUMEN
BACKGROUND: Moyamoya disease (MMD) is a cerebrovascular disease with unknown cause. Patients with MMD disease usually experience transient neurological events (TNEs) after revascularization surgery. This retrospective single-center study was aimed to explore the risk factors of postoperative TNEs after surgical revascularization in patients with MMD. METHODS: We selected 324 patients who underwent surgical revascularization between January 2017 and September 2022 in our center. The perioperative characteristics of the patients were recorded and the outcome was TNEs after surgery. An analysis of risk factors contributing to postoperative TNEs by using logistic regression model. RESULTS: Three hundred twelve patients were enrolled, and the incidence of postoperative TNEs was 34% in our study. Males were more likely to suffer from postoperative TNEs (OR = 2.344, p = 0.002). Preoperative ischemic presentation (OR = 1.849, p = 0.048) and intraoperative hypotension (OR = 2.332, p = 0.002) were associated with postoperative TNEs. Compared to patients with blood type O, patients with blood type A (OR = 2.325, p = 0.028), B (OR = 2.239, p = 0.027) and AB (OR = 2.938, p = 0.019) had a significantly higher incidence of postoperative TNEs. A risk prediction model for postoperative TNEs was established, and the established risk prediction area under the receiver operating characteristic curve (ROC) of the model was 0.741. CONCLUSIONS: Males, preoperative ischemic presentation and intraoperative hypotension were associated with postoperative TNEs. We also found a possible link between postoperative TNEs and ABO blood types after surgical revascularization for moyamoya patients.
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Revascularización Cerebral , Hipotensión , Enfermedad de Moyamoya , Masculino , Humanos , Estudios Retrospectivos , Enfermedad de Moyamoya/cirugía , Enfermedad de Moyamoya/complicaciones , Revascularización Cerebral/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Hipotensión/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Both sepsis and AKI are diseases of major concern in intensive care unit (ICU). This study aimed to evaluate the excess mortality attributable to sepsis for acute kidney injury (AKI). METHODS: A propensity score-matched analysis on a multicenter prospective cohort study in 18 Chinese ICUs was performed. Propensity score was sequentially conducted to match AKI patients with and without sepsis on day 1, day 2, and day 3-5. The primary outcome was hospital death of AKI patients. RESULTS: A total of 2008 AKI patients (40.9%) were eligible for the study. Of the 1010 AKI patients with sepsis, 619 (61.3%) were matched to 619 AKI patients in whom sepsis did not develop during the screening period of the study. The hospital mortality rate of matched AKI patients with sepsis was 205 of 619 (33.1%) compared with 150 of 619 (24.0%) for their matched AKI controls without sepsis (p = 0.001). The attributable mortality of total sepsis for AKI patients was 9.1% (95% CI: 4.8-13.3%). Of the matched patients with sepsis, 328 (53.0%) diagnosed septic shock. The attributable mortality of septic shock for AKI was 16.2% (95% CI: 11.3-20.8%, p < 0.001). Further, the attributable mortality of sepsis for AKI was 1.4% (95% CI: 4.1-5.9%, p = 0.825). CONCLUSIONS: The attributable hospital mortality of total sepsis for AKI were 9.1%. Septic shock contributes to major excess mortality rate for AKI than sepsis. REGISTRATION FOR THE MULTICENTER PROSPECTIVE COHORT STUDY: registration number ChiCTR-ECH-13003934.
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Lesión Renal Aguda , Sepsis , Humanos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/mortalidad , Unidades de Cuidados Intensivos , Estudios Prospectivos , Sepsis/complicaciones , Sepsis/mortalidad , Choque Séptico/diagnósticoRESUMEN
BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.
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Asma , Productos Biológicos , Pólipos Nasales , Rinitis , Sinusitis , Humanos , Asma/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Enfermedad Crónica , Consenso , Pólipos Nasales/complicaciones , Pólipos Nasales/tratamiento farmacológico , Omalizumab/uso terapéutico , Calidad de Vida , Rinitis/complicaciones , Rinitis/tratamiento farmacológico , Sinusitis/complicaciones , Sinusitis/tratamiento farmacológico , Esteroides/uso terapéuticoRESUMEN
BACKGROUND: The multiple symptoms of Sjögren's syndrome lead patients affected by this disease to seek medical advice from different medical disciplines and specialists. Diagnoses are often made many years after initial onset, resulting in mental and physical exhaustion and misunderstandings. PURPOSE: This study was designed to explore the health-seeking experiences of patients with Sjögren's syndrome. METHODS: Qualitative research methods and purposive sampling were used. Fourteen patients with Sjögren's syndrome were interviewed by the first author, and the collected data were analyzed using content analysis. RESULTS: Four themes were revealed from the data, including: (1) distressing symptoms; (2) difficulty in diagnosis; (3) concerns about drug side effects; and (4) facing the disease. The participants initially sought medical attention when they began experiencing early onset symptoms that caused discomfort or annoyance. Their doctors' failure to provide proper diagnoses during the long health-seeking process caused a great deal of suffering to the participants. Although related medications should be taken for life, the participants reported taking lower-than-prescribed dosages out of fear of side-effects. The participants explored their process of coping with the disease, which began with denial and ended with acceptance. By learning from their health-seeking process, participants realized that they needed to take proper care of themselves, adapt to life with their disease, and control related symptoms. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: To facilitate the early diagnosis of Sjögren's syndrome, healthcare professionals should improve their awareness of this condition and refer patients with related symptoms to rheumatologists and immunologists. Effective early diagnosis and treatment can help these patients reduce the time and effort involved in unproductive doctor's visits, allowing them to better continue as productive members of society and to maintain a good quality of life.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Síndrome de Sjögren , Humanos , Calidad de Vida , Síndrome de Sjögren/diagnóstico , Adaptación Psicológica , FatigaRESUMEN
The Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome (KLHL 11-PNS) was first identified in 2019. This novel antibody, targeting the intracellular KLHL 11 antigen, can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. It is thought to be a biomarker for a T-cell autoimmunity response. The most likely immunopathogenesis of KLHL 11-PNS appears to be linked to cytotoxic T-cell-mediated neuronal injury and loss. Patients have adult-male predilection, rhombencephalitis (brainstem and / or cerebellar involvement), and a robust oncological correlation with testicular germ cell tumors (predominately seminoma). Brain magnetic resonance imaging demonstrated T2 / fluid-attenuated inversion recovery hyperintensities and atrophy of the temporal lobe, cerebellum, and brainstem. Most patients responded poorly to immunotherapy and oncotherapy and thus had a poor long-term prognosis. We review the literature and provide an update of current knowledge regarding KLHL 11-PNS, including epidemiology, underlying mechanism, clinical presentations, paraclinical and oncological findings, diagnostic workup, and treatment approaches.
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Neoplasias de Células Germinales y Embrionarias , Síndromes Paraneoplásicos del Sistema Nervioso , Síndromes Paraneoplásicos , Neoplasias Testiculares , Adulto , Autoanticuerpos , Humanos , Masculino , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , Síndromes Paraneoplásicos del Sistema Nervioso/terapiaRESUMEN
BACKGROUND: Cervical cancer is the most fatal gynecological carcinoma in the world. It is urgent to explore novel prognostic biomarkers and intervention targets for cervical cancer. METHODS: Through integrated quantitative proteomic strategy, we investigated the protein expression profiles of cervical cancer; 28 fresh frozen tissue samples (11 adenocarcinoma (AC), 12 squamous cell carcinoma (SCC) and 5 normal cervixes (HC)) were included in discover cohort; 45 fresh frozen tissue samples (19 AC, 18 SCC and 8 HC) were included in verification cohort; 140 paraffin-embedded tissues samples of cervical cancer (85 AC and 55 SCC) were used for immunohistochemical evaluation (IHC) of coatomer protein subunit alpha (COPA) as a prognostic biomarker for cervical cancer; how deficiency of COPA affects cell viability and tumorigenic ability of cervical cancer cells (SiHa cells and HeLa cells) were evaluated by cell counting kit-8 and clone formation in vitro. RESULTS: We identified COPA is a potential prognostic biomarker for cervical cancer in quantitative proteomics analysis. By retrospective IHC analysis, we additionally verified the proteomics results and demonstrated moderate or strong IHC staining for COPA is an unfavourable independent prognostic factor for cervical cancer. We also identified COPA is a potential pharmacological intervention target of cervical cancer by a series of in vitro experiments. CONCLUSION: This study is the first to demonstrate that COPA may contribute to progression of cervical cancer. It can serve as a potential prognostic biomarker and promising intervention target for cervical cancer.
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Proteína Coatómero , Neoplasias del Cuello Uterino , Biomarcadores , Biomarcadores de Tumor/metabolismo , Femenino , Células HeLa , Humanos , Pronóstico , Proteómica , Estudios Retrospectivos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/metabolismoRESUMEN
Seizure is one of the manifestations of central nervous system inflammatory demyelinating diseases, which mainly include multiple sclerosis (MS), aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Acute symptomatic seizures secondary to MS/AQP4-NMOSD/MOGAD occur in the acute phase of the diseases, and are more frequent in MOGAD. In contrast, recurrent nonprovoked seizures, mainly attributed to autoimmune-associated epilepsy, occur in the nonacute phase of the diseases. Seizures in MS/AQP4-NMOSD/MOGAD mostly have a focal onset. MS patients with concomitant systemic infections, earlier onset, and greater disease activity are more likely to have seizures, whereas factors such as greater MS severity, the presence of status epilepticus, and cortical damage indicate a greater risk of developing epilepsy. In MOGAD, cerebral cortical encephalitis and acute disseminated encephalomyelitis (ADEM)-like phenotypes (predominately ADEM and multiphasic disseminated encephalomyelitis) indicate a greater seizure risk. Multiple relapses with ADEM-like phenotypes predict epilepsy in pediatrics with MOGAD. Pathophysiologically, acute symptomatic seizures in MS are associated with neuronal hyperexcitability secondary to inflammation and demyelination. Chronic epilepsy in MS is largely due to gliosis, neuronal dysfunction, and synaptic abnormalities. The mainstay of treatment for seizures secondary to MS/AQP4-NMOSD/MOGAD consists of immunotherapy along with antiseizure medications. This critical review discusses the most-updated evidence on epidemiology, clinical correlates, and inflammatory mechanisms underlying seizures and epilepsy in MS/AQP4-NMOSD/MOGAD. Treatment cautions including drug-drug interactions and the impact of treatments on the diseases are outlined. We also highlight pitfalls and challenges in managing such patients and future research perspectives to address unsolved questions.
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Epilepsia , Esclerosis Múltiple , Neuromielitis Óptica , Acuaporina 4 , Autoanticuerpos , Niño , Epilepsia/etiología , Humanos , Esclerosis Múltiple/complicaciones , Glicoproteína Mielina-Oligodendrócito/metabolismo , Neuromielitis Óptica/complicaciones , ConvulsionesRESUMEN
OBJECTIVE: We aimed to evaluate the assessment and management of epilepsy with anxiety and depression, and their clinical practice based on a survey. METHODS: A cross-sectional survey of epilepsy health professionals was undertaken in Zhejiang Province using the modified International League Against Epilepsy (ILAE) Psychology Task Force questionnaire. We recorded the characteristics of participants and the practice of screening, referral, and treatment for depression and anxiety disorders. A total of 146 participants joined in the survey, of which 76.0% were neurologists, and 69 participants were the member of the Zhejiang Association Against Epilepsy (ZAAE). RESULTS: This survey revealed that almost all participants (87.7%) agreed that screening for depression and anxiety in patients with epilepsy (PWEs) was very important; however, the frequency of screening was very low (41.1% of participants screened less than 10% of patients, and 34.2% participants screened between 10% and 30% of patients). A higher frequency of screening was reported in the member group and compared with that in the non-member group (Pâ¯=â¯0.025). The main barrier to screening was the lack of time during clinic visits: 81.5% participants included screening questions as part of their clinical review. When anxiety/depression was diagnosed, the next step should be to refer patients to a psychiatrist (78.1%). No standardized procedures and lack of mental health specialists trained to assess and/or manage PWEs, were the main barriers to follow-up assessment and management. Lack of appropriately trained mental health specialists was also the main barrier to psychological treatment for depression and anxiety. CONCLUSION: This survey highlighted that epilepsy healthcare professionals in Zhejiang province agreed on the importance of screening for psychiatric comorbidities in PWEs; however, the screening and management were actually insufficient. Certain barriers to screening, referral, and treatment were presented and improvements were recommended.
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Depresión , Epilepsia , Ansiedad/diagnóstico , Ansiedad/epidemiología , Ansiedad/etiología , Trastornos de Ansiedad , Estudios Transversales , Depresión/diagnóstico , Depresión/epidemiología , Depresión/etiología , Epilepsia/complicaciones , Epilepsia/diagnóstico , Epilepsia/epidemiología , Humanos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Pre-existing chronic pain has been associated with severe postoperative pain. In this study, we sought to prospectively analyse the association between the duration of chronic low back pain and the intensity of acute postoperative pain after lumbar fusion surgery. METHODS: A total of 330 patients who underwent lumbar fusion surgery were divided into three groups (chronic low back pain less than 1 year, one to 5 years, and more than 5 years) based on the duration of chronic pain. On the first postoperative day, the maximum pain scores of each patient were recorded during the day and at night. Bivariate correlation and logistic regression were performed to identify relationships between acute postoperative pain and related variables (age, sex, smoking history, body mass index, operation history, duration of surgery, level of preoperative pain, aetiology of back pain, Self-rating Anxiety Scale, Self-rating Depression Scale, FRAIL scale, and duration of chronic low back pain). If the postoperative pain score was > 3 when the patient reported was at rest, the patients were treated with postoperative intravenous self-controlled analgesia or rescue analgesics if necessary. RESULTS: There was an association between severe acute postoperative pain and the duration of chronic low back pain. In terms of VAS day, multivariable logistic regression showed the duration of chronic low back pain was not statistically significant (OR = 2.48, 95% CI: 0.900 to 6.828, p = 0.0789). The result is uncertain because the confidence interval included the null after controlling for SAS, SDS, BMI, and aetiology of back pain. In terms of VAS night, patients with a duration of chronic low back pain of more than 5 years were more likely having moderate to severe acute postoperative pain (VAS > 3) compared to patients with a duration of chronic low back pain less than 1 year (OR = 3.546, 95% CI: 1.405 to 8.95, p = 0.0074). Hospital stay, the pain score on the day of discharge and the pain score after 3 months displayed no significant difference among the three groups (P > 0.05). However, the need for postoperative rescue analgesics was different among the three groups (P < 0.05). CONCLUSION: The longer the duration of chronic pain was, the higher the incidence of moderate to severe acute postoperative pain was and the greater the amount of analgesics required after surgery. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registration Center ( http://www.chictr.org.cn/index.aspx , clinical trial number: ChiECRCT20200165, date of registration: July 6, 2020).
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Dolor Crónico , Dolor de la Región Lumbar , Analgésicos/uso terapéutico , Dolor de Espalda , Dolor Crónico/epidemiología , Dolor Crónico/etiología , Humanos , Dolor de la Región Lumbar/cirugía , Dimensión del Dolor , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/etiologíaRESUMEN
PURPOSE: To evaluate the value of texture analysis (TA) of conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in the differential diagnosis between sinonasal non-Hodgkin's lymphoma (NHL) and squamous cell carcinoma (SCC). METHODS: Forty-two patients with sinonasal SCC and 30 patients with NHL were retrospectively enrolled. TAs were performed on T2-weighted image (T2WI), apparent diffusion coefficient (ADC) and contrast-enhanced T1-weighted image (T1WI). Texture parameters, including mean value, skewness, kurtosis, entropy and uniformity were obtained and compared between sinonasal SCC and NHL groups. Receiver-operating characteristic (ROC) curves and logistic regression analyses were used to evaluate the diagnostic value and identify the independent TA parameters. RESULTS: The mean value and entropy of ADC, and mean value of contrast-enhanced T1WI were significantly lower in the sinonasal NHL group than those in the SCC group (all P < 0.05). ROC analysis indicated that the entropy of ADC had the best diagnostic performance (AUC 0.832; Sensitivity 0.95; Specificity 0.67; Cutoff value 6.522). Logistic regression analysis showed that the entropy of ADC (P = 0.002, OR = 26.990) was the independent parameter for differentiating sinonasal NHL from SCC. CONCLUSION: TA parameters of conventional MRI and DWI, particularly the entropy value of ADC, might be useful in the differentiating diagnosis between sinonasal NHL and SCC.
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Carcinoma de Células Escamosas , Linfoma no Hodgkin , Neoplasias de los Senos Paranasales , Humanos , Estudios Retrospectivos , Imagen de Difusión por Resonancia Magnética , Imagen por Resonancia Magnética/métodos , Linfoma no Hodgkin/diagnóstico por imagen , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Curva ROC , Diagnóstico Diferencial , Neoplasias de los Senos Paranasales/diagnóstico por imagen , Carcinoma de Células Escamosas de Cabeza y Cuello , Sensibilidad y EspecificidadRESUMEN
Six kinds of dithiocarbamates (DTCs) were synthesized from three linear amines with different amino numbers, two polyether amines with different molecular weights, and one branched amine with benzene rings, respectively. The conditions affecting oil removal rate and floc rising time of DTC were studied using simulated oily wastewater. Furthermore, the effects of the molecular structure of DTC on oil removal efficiency, floc morphology, floc rising time, and floc adhesion were investigated. When the conditions were optimal, the oil removal efficiency of DTC synthesized from polyethylene polyamine was 95.14%, which was higher than other DTCs. Meanwhile, the ferrous ion was the most suitable chelating metal ion for DTC than other transition metal ions. The increase of amino groups in the initiators improves the oil removal efficiency of DTC, while the linear structural DTC exhibits a low oil removal efficiency due to a lack of network structural flocs. The introduction of polyether structure helps reduce the volume of the flocs and make them compact, but it also increases the adhesion of the floc on the metal surface. The introduction of bisphenol A phenol amino resin structure induces the generation of the flocs in oil wastewater and improves the oil removal efficiency.
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Aceites , Aguas Residuales , Aminas , Floculación , Estructura MolecularRESUMEN
OBJECTIVE: To observe the recovery of urinary continence through postoperative rehabilitation training after robot-assisted laparoscopic radical prostatectomy (RARP) versus that after traditional laparoscopic radical prostatectomy (LRP). METHODS: This study included 64 cases of urinary incontinence after surgically treated for PCa from May 2017 to February 2021, 32 by RARP and the other 32 by LRP as the controls. All the patients received standard urinary continence rehabilitation training and routine nursing care postoperatively, followed by comparison of the rate and time of urinary incontinence recovery and the patients' scores on the quality of life (QOL) and satisfaction with treatment between the two groups. RESULTS: There were no statistically significant differences in age, PSA level or pathological stage between the two groups of patients (P > 0.05). After standard urinary continence rehabilitation training, the patients in the RARP group, compared with those in the LRP control, showed a lower grade of urinary incontinence (χ2 = 6.483, P = 0.039), a shorter mean duration of urinary incontinence per day, an earlier recovery of urinary continence (χ2 = 4.73, P = 0.030 at 1ï¼3 months; χ2 = 12.696, P < 0.001 at 4ï¼6 months), a higher rate of overall recovery (χ2 = 13.396, P = 0.004), and higher scores on QOL and satisfaction with treatment. CONCLUSION: RARP can effectively improve the recovery from postoperative urinary incontinence in PCa patients.