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1.
Transl Pediatr ; 13(7): 1201-1209, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39144427

RESUMEN

Background: Sialyllacto-N-tetraose b (LSTb) is a component of human milk oligosaccharides. Due to its low concentration, the impact of LSTb on neurodevelopment remains largely unexplored. It is worth studying whether LSTb should be added to infant formula to simulate breast milk. This study aimed to investigate the effect of LSTb on the development of motor neurons of the central nervous system using a transgenic zebrafish model. Methods: Transgenic (Tg) zebrafish line (Hb9:GFP) was incubated with LSTb, and the axonal growth of caudal primary (CaP) neurons was assessed. Locomotor behavior was evaluated, and RNA sequencing (RNA-seq) was performed to identify the differentially expressed genes (DEGs). The expression of Slit2 and Slit3, genes involved in axon guidance, was further analyzed through real-time polymerase chain reaction (real-time PCR) and whole-mount in situ hybridization. Results: There was a significant increase in the number and length of CaP axon branches, suggesting that LSTb promotes CaP development. Behavioral analysis revealed enhanced locomotor activity in LSTb-treated larvae, indicating improved motor function. RNA-seq analysis identified 5,847 DEGs related to central nervous system neuron differentiation, including Slit2 and Slit3, which are known to contribute to axon guidance. In situ hybridization confirmed increased Slit2 expression in the central nervous system of LSTb-treated larvae. Conclusions: LSTb significantly influences motor neuron development, potentially through the upregulation of Slit2 and Slit3. This research provides valuable insights into the role of LSTb in neurodevelopment.

2.
BMC Pediatr ; 24(1): 420, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38951748

RESUMEN

BACKGROUND: Although most children with febrile seizures (FS) have a favorable prognosis, some experience recurrence within 1-3 years. Age, peak temperature, and family history are now recognized as important risk factors for FS recurrence, yet studies in this area are lacking in China. This study aimed to investigate the risk factors for FS recurrence in children in Nantong, China, and to develop a prediction model. METHODS: This retrospective cohort study analyzed 463 children diagnosed with febrile seizures (FS) who presented to the Affiliated Hospital of Nantong University between January 2015 and June 2020. Basic information, disease characteristics, and laboratory and imaging data were collected. A follow-up survey was conducted one year post-discharge to assess the recurrence status of FS in children. Univariate logistic regression and random forest models were used to identify and rank the predictive ability of risk factors for recurrence. RESULTS: Of the 463 children with FS, 70 experienced recurrences within 1 year of discharge, resulting in a one-year recurrence rate of 15%. Age (OR = 0.61, 95% CI: 0.46, 0.80, P < 0.001), duration of the first episode (OR = 1.03, 95% CI: 1.00, 1.06, P = 0.040), and peak temperature (OR = 0.68, 95% CI: 0.47, 0.98, P = 0.036) were identified as independent risk factors for FS recurrence. Age had the highest relative importance in predicting FS recurrence, followed by the duration of the first episode, with an area under the ROC curve of 0.717. CONCLUSION: Young age and duration of the first seizure are important independent risk factors for FS recurrence and are key considerations for predicting recurrence. Further research is needed to confirm the potential use of Neutrophil-lymphocyte ratio (NLR) as a predictor of FS recurrence.


Asunto(s)
Recurrencia , Convulsiones Febriles , Humanos , Convulsiones Febriles/epidemiología , Convulsiones Febriles/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Masculino , Femenino , China/epidemiología , Lactante , Preescolar , Factores de Edad , Estudios de Seguimiento , Niño , Pronóstico
3.
J Gastroenterol Hepatol ; 39(8): 1695-1703, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38804845

RESUMEN

BACKGROUND AND AIM: Hydronidone (HDD) is a novel pirfenidone derivative developed initially to reduce hepatotoxicity. Our previous studies in animals and humans have demonstrated that HDD treatment effectively attenuates liver fibrosis, yet the underlying mechanism remains unclear. This study aimed to investigate whether HDD exerts its anti-fibrotic effect by inducing apoptosis in activated hepatic stellate cells (aHSCs) through the endoplasmic reticulum stress (ERS)-associated mitochondrial apoptotic pathway. METHODS: The carbon tetrachloride (CCl4)- and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver fibrosis models were used for in vivo studies. In vitro studies were conducted using the human hepatic stellate cell line LX-2. The apoptotic effect of HDD on aHSCs was examined using TUNEL and flow cytometry assays. The small interfering RNA (siRNA) technique was employed to downregulate the expression of interest genes. RESULTS: HDD treatment significantly promoted apoptosis in aHSCs in both the CCl4- and DDC-induced liver fibrosis in mice and LX-2 cells. Mechanistic studies revealed that HDD triggered ERS and subsequently activated the IRE1α-ASK1-JNK pathway. Furthermore, the influx of cytochrome c from the mitochondria into the cytoplasm was increased, leading to mitochondrial dysfunction and ultimately triggering apoptosis in aHSCs. Notably, inhibition of IRE1α or ASK1 by siRNA partially abrogated the pro-apoptotic effect of HDD in aHSCs. CONCLUSIONS: The findings of both in vivo and in vitro studies suggest that HDD induces apoptosis in aHSCs via the ERS-associated mitochondrial apoptotic pathway, potentially contributing to the amelioration of liver fibrosis.


Asunto(s)
Apoptosis , Estrés del Retículo Endoplásmico , Células Estrelladas Hepáticas , Cirrosis Hepática , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Apoptosis/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Animales , Humanos , Cirrosis Hepática/patología , Cirrosis Hepática/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/inducido químicamente , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Endorribonucleasas/metabolismo , Endorribonucleasas/genética , Tetracloruro de Carbono , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Masculino , Línea Celular , Piridonas/farmacología , Ratones , MAP Quinasa Quinasa Quinasa 5/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos
4.
Int Wound J ; 21(1): e14544, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38272812

RESUMEN

Colorectal endoscopic mucosal resection (EMR) is associated with the risk of postoperative wound infections, prompting investigations into effective prophylactic measures. This meta-analysis aimed to evaluate the efficacy of various prophylactic interventions in reducing the incidence of wound infections following EMR. Adhering to PRISMA guidelines, we conducted a comprehensive search across multiple databases for randomized controlled trials (RCTs) and cohort studies from 2015 to 2022. We included studies that compared the efficacy of antibiotic prophylaxis and antiseptic measures, with clear data on post-procedure infection rates. Eight studies met our inclusion criteria, and data were extracted for meta-analysis. The risk of bias was assessed using the Cochrane Collaboration tool and the Newcastle-Ottawa Scale. The meta-analysis included 3765 patients from eight RCTs. Prophylactic antibiotics (cefixime and cefuroxime) showed moderate to high efficacy, with infection rates as low as 0% and 0.76%. Prophylactic endoscopic closure and clipping showed the highest efficacy, with zero reported infections. The standardized surgical site infection prevention bundle had lower effectiveness, with an infection incidence of 3.83%. The risk of bias assessment indicated potential performance bias due to lack of blinding, but overall evidence quality was upheld by proper random sequence generation and diligent outcome data monitoring. The effectiveness of specific prophylactic measures, notably prophylactic antibiotics and mechanical closure techniques, has been shown in significantly reducing the risk of wound infections following colorectal EMR.


Asunto(s)
Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Humanos , Infección de la Herida Quirúrgica/epidemiología , Profilaxis Antibiótica , Antibacterianos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico
6.
Math Biosci Eng ; 20(2): 2716-2731, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36899554

RESUMEN

Cystatin C, the full name of cystatin C, is one of the most potent cathepsin inhibitors currently known, which can strongly inhibit cathepsin in lysosomes and regulate the level of intracellular proteolysis. Cystatin C plays a very broad role in the body. High temperature-induced brain injury leads to very serious damage to brain tissue, such as cell inactivation, brain tissue edema, etc. At this time, cystatin C can play a crucial role. Based on the research on the expression and role of cystatin C in high temperature-induced brain injury in rats, this paper draws the following conclusions: high temperature can cause very serious damage to the brain tissue of rats, which can seriously lead to death. Cystatin C has a protective effect on brain cells and cerebral nerves. When the brain is damaged by high temperature, cystatin C can relieve the damage of high temperature to the brain and protect brain tissue. In this paper, a detection method for cystatin C with more outstanding performance is proposed, and compared with the traditional detection method, the detection method in this paper is verified to have more accurate accuracy and excellent stability through comparative experiments. Compared with traditional detection methods, it is more worthwhile to use and is a better detection method.


Asunto(s)
Lesiones Encefálicas , Hipertermia Inducida , Animales , Ratas , Encéfalo/metabolismo , Lesiones Encefálicas/metabolismo , Catepsinas/metabolismo , Cistatina C/metabolismo
7.
Brain Behav ; 13(3): e2890, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36738135

RESUMEN

BACKGROUND: Ischemic stroke is a clinical emergency caused by insufficient intracranial blood supply, which eventually leads to brain tissue necrosis and neurological impairment. Predictive nursing intervention has achieved impressive success in the nursing of multiple surgeries. However, the role of predictive nursing intervention in the care of patients with ischemic stroke remains unclear. METHODS: This study was a randomized controlled trial. Based on the inclusion and exclusion criteria, 126 patients were randomly assigned into two groups, namely the control group and the predictive nursing intervention group. Both groups were treated with thrombolytic therapy with alteplase. The patients in the control group were given routine nursing intervention and the predictive nursing intervention group received additional predictive care. Neurologic functions and cognitive impairment were evaluated by National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer assessment (FMA), Montreal cognitive assessment (MoCA), and mini-mental state examination (MMSE) scales, respectively. Door-to-Needle Times, venous thromboembolism (VTE)-related parameters, and complications were recorded. RESULTS: Predictive nursing intervention significantly shortened the Door-to-Needle Times and enhanced the peak/average femoral venous blood flow and femoral venous diameter. In addition, predictive nursing intervention improved the NIHSS, FMA, MMSE, and MoCA scores and remarkably reduced the recurrence of ischemic stroke, deep vein thrombosis and gingival bleeding. CONCLUSION: Predictive nursing intervention is beneficial to improve the effects of thrombolytic therapy in patients with ischemic stroke, which improves the neurological, cognitive and motor functions of patients, and reduces the occurrence of complications, suggesting an important clinical application value.


Asunto(s)
Disfunción Cognitiva , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular Isquémico/complicaciones , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/diagnóstico , Activador de Tejido Plasminógeno , Pruebas de Estado Mental y Demencia
8.
J Dairy Sci ; 106(3): 1533-1548, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36710180

RESUMEN

A growing stream of research suggests that probiotic fermented milk has a good effect on nonalcoholic fatty liver disease. This work aimed to study the beneficial effects of Lactobacillus rhamnosus hsryfm 1301 fermented milk (fermented milk) on rats with nonalcoholic fatty liver disease induced by a high-fat diet. The results showed that the body weight and the serum levels of total cholesterol, total glyceride, low-density lipoprotein, alanine transaminase, aspartate aminotransferase, free fatty acid, and reactive oxygen species were significantly increased in rats fed a high-fat diet (M) for 8 wk, whereas high-density lipoprotein cholesterol and superoxide dismutase were significantly decreased. However, the body weight and the serum levels of total cholesterol, total glyceride, alanine transaminase, aspartate aminotransferase, free fatty acid, reactive oxygen species, interleukin-8, tumor necrosis factor-α, and interleukin-6 were significantly decreased with fermented milk (T) for 8 wk, and the number of fat vacuoles in hepatocytes was lower than that in the M group. There were significant differences in 19 metabolites in serum between the M group and the C group (administration of nonfermented milk) and in 17 metabolites between the T group and the M group. The contents of 7 different metabolites, glycine, glycerophosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, thioetheramide-PC, d-aspartic acid, oleic acid, and l-glutamate, were significantly increased in the M group rat serum, and l-palmitoyl carnitine, N6-methyl-l-lysine, thymine, and 2-oxadipic acid were significantly decreased. In the T group rat serum, the contents of 8 different metabolites-1-O-(cis-9-octadecenyl)-2-O-acetyl-sn-glycero-3-phosphocholine, acetylcarnitine, glycine, glycerophosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, d-aspartic acid, oleic acid, and l-glutamate were significantly decreased, whereas creatinine and thymine were significantly increased. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that 50 metabolic pathways were enriched in the M/C group and T/M group rat serum, of which 12 metabolic pathways were significantly different, mainly distributed in lipid metabolism, amino acid, and endocrine system metabolic pathways. Fermented milk ameliorated inflammation, oxygenation, and hepatocyte injury by regulating lipid metabolism, amino acid metabolic pathways, and related metabolites in the serum of rats with nonalcoholic fatty liver disease.


Asunto(s)
Lacticaseibacillus rhamnosus , Enfermedad del Hígado Graso no Alcohólico , Ratas , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/veterinaria , Leche/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Alanina Transaminasa , Ácido Glutámico , Ácido D-Aspártico/metabolismo , Ácido D-Aspártico/farmacología , Ácido Oléico/metabolismo , Timina/metabolismo , Timina/farmacología , Glicéridos/metabolismo , Glicéridos/farmacología , Aspartato Aminotransferasas , Peso Corporal , Glicina/metabolismo , Glicina/farmacología , Colesterol/metabolismo , Dieta Alta en Grasa , Hígado/metabolismo
9.
Cell Death Discov ; 8(1): 482, 2022 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-36473844

RESUMEN

Congenital hypothyroidism (CH) will cause cognitive impairment in the condition of delayed treatment. The hippocampus is one of the most affected tissues by CH, in which the functional structures of hippocampal neurons manifest deficiency due to aberrant expression of effector molecules. The Ca2+/Calmodulin-dependent protein kinase, CaMKIV, is downregulated in the hippocampal neurons, influencing the growth of dendritic spines in response to CH. However, the underlying mechanism is not fully elucidated. In the present study, the early growth response factor 3 (EGR3) was regulated by CaMKIV in the hippocampal neurons of CH rat pups, as was analyzed by transcriptome sequencing and in vitro cell experiments. EGR3 localized within hippocampal neurons in CA1, CA3, and dentate gyrus regions. Deficient EGR3 in the primary hippocampal neurons significantly reduced the density of dendritic spines by downregulating the expression of BDNF, and such effects could be rescued by supplementing recombinant BDNF protein. Taken together, CH mediates cognitive impairment of pups through the inactivation of CaMKIV in the hippocampal neurons, which decreases the expression of EGR3 and further reduces the production of BDNF, thereby impairing the growth of dendritic spines. Identifying CaMKIV/EGR3/BDNF pathway in the hippocampal neurons in the context of CH will benefit the drug development of intellectual disability caused by CH.

10.
Front Oncol ; 12: 964115, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35965580

RESUMEN

Objectives: There is an urgent need for biomarkers that predict the survival outcome of patients diagnosed with metastatic pancreatic cancer, undergoing systemic chemotherapy. This study aimed to identify biomarkers associated with the survival of mPC patients treated with modified FOLFIRINOX (mFOLFIRINOX) as first-line chemotherapy. Methods: This was a retrospective study of 30 patients with mPC who received mFOLFIRINOX between October 2018 and March 2021. Data on carcinoembryonic antigen (CEA), cancer antigen (CA)199, interleukin (IL)-6, C-reactive protein (CRP), neutrophils, platelets, lymphocytes, and albumin were collected and dichotomized using the upper or lower limit, as appropriate. These markers were examined for their association with progression-free survival (PFS). A receiver operating characteristic (ROC) curve analysis was used to explore a suitable model to predict mFOLFIRINOX effectiveness. Results: IL-6 and CRP levels were associated with poor progression (P = 0.004 and P = <0.001, respectively) of mPC. The high IL-6 level was an independent poor prognostic factor for PFS (HR=4.66, 95%CI: 1.32-16.37, P=0.016) in the multivariable analysis. Patients with high IL-6 levels had a shorter PFS than those with low IL-6 levels (median PFS: 257 vs. 150 days, P=0.020). An increase in IL-6 and CRP levels during chemotherapy positively correlated with disease progression (P = <0.001 for both). The model combining IL-6 with CRP levels helped predict the outcomes of mPC patients treated with mFOLFIRINOX (AUC: 0.811, 95%CI: 0.639-0.983, P=0.003). Conclusions: The serum levels of IL-6 and CRP might be considered as valuable biomarkers in predicting the outcomes of patients with mPC who received the mFOLFIRINOX regimen.

11.
BMJ Open ; 12(3): e056395, 2022 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-35288389

RESUMEN

OBJECTIVE: To assess the association between blood pressure (BP) control and frailty among middle-aged and older populations with hypertension in China from 2013 to 2018. DESIGN: Prospective longitudinal study. SETTING: This study analysed data from the China Health and Retirement Longitudinal Study, a nationally representative survey administered in 28 provinces of China. PARTICIPANTS: A total of 3254 participants diagnosed with hypertension previous to 2013 were taken into analysis. 1932 participants who were not frail in 2013 were enrolled to calculate relative risk. OUTCOME MEASURES: The frailty score was constructed following Rookwood's Cumulative deficit frailty index, with a score >0.25 defined as frailty (outcome variable). The self-reported status of BP control (exposure variable) represented the general status of the participant's BP level. A fixed-effects model was used to analyse the association between BP control and frailty. A Cox proportional hazard model was further used to further calculate the relative risk of frailty for different BP control levels. RESULTS: The fixed-effects model showed that compared with well-controlled BP, poorly controlled BP exhibited a positive association with frailty score (ß=0.015; 95% CI 0.011 to 0.019; p<0.001). The Cox proportional hazard model also revealed a higher risk of frailty in the poorly controlled group (HR=1.96; 95% CI 1.49 to 2.56; p<0.001). Based on subgroup analyses, poorly controlled BP was positively associated with frailty in respondents aged <60 years old (fix-effects model: ß=0.015, p=0.021; Cox model: HR=2.25, p<0.001), but not significant among those aged ≥75 years old. CONCLUSIONS: We provide new evidence of a negative association between BP control and frailty risk, but the findings differ among different age groups. Individualised strategies for BP management should be developed, especially for older hypertension patients.


Asunto(s)
Fragilidad , Hipertensión , Anciano , Presión Sanguínea , China/epidemiología , Fragilidad/diagnóstico , Fragilidad/epidemiología , Humanos , Hipertensión/epidemiología , Estudios Longitudinales , Persona de Mediana Edad , Estudios Prospectivos
12.
Colorectal Dis ; 24(1): 68-76, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34611964

RESUMEN

AIM: Systemic chemotherapy combining biological targeted therapies is the standard therapy for patients with metastatic colorectal cancer (mCRC), but effective markers are needed to identify clinical responders. Circulating tumour cells (CTCs) have been associated with prognosis in patients with mCRC. This study aimed to explore the relationship between CTC number and the clinical response of patients with advanced CRC. METHOD: Epithelial cell adhesion molecule-independent enrichment and CD45- fluorescence in situ hybridization immunofluorescence were used to detect peripheral blood CTCs in 79 patients with advanced CRC. Fisher's exact test and Spearman's rank correlation coefficient were used to analyse the correlation between CTC number and efficacy of chemotherapy. Kaplan-Meier and Cox regression analyses were used to evaluate progression-free survival (PFS). RESULTS: Among the evaluable patients, CTCs were significantly correlated with clinical response (r =4.891, p = 0.031). High CTC numbers were associated with a poor treatment response (r = -0.250, p = 0.027). Dynamic decrease in CTC number was associated with clinical response (p = 0.046). High baseline CTC number and carcinoembryonic antigen levels were prognostic factors for unfavourable PFS in multivariable analysis [hazard ratio (HR) = 3.30, p = 0.011 and HR = 2.04, p = 0.044, respectively]. Compared with the CTC-positive group, the CTC-negative group showed superior PFS (median PFS 15.53 vs. 9.43 months, p = 0.041) among CRC patients receiving first-line treatment. CONCLUSION: CTC number is a feasible biomarker for predicting outcomes in mCRC patients receiving systemic chemotherapy.


Asunto(s)
Neoplasias Colorrectales , Células Neoplásicas Circulantes , Biomarcadores de Tumor , Neoplasias Colorrectales/patología , Humanos , Hibridación Fluorescente in Situ , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Pronóstico
13.
Neurosci Lett ; 756: 135964, 2021 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-34022266

RESUMEN

Differential diagnosis of Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear paralysis (PSP) is challenging. This study aimed to investigate the expression of phosphorylated α-synuclein (p-α-syn) and phosphorylated tau-protein (p-tau) in sural nerves from patients with PD, MSA and PSP to find biomarkers for differential diagnosis. Clinical evaluations and sural nerve biopsies were performed on 8 PD patients, 8 MSA patients, 6 PSP patients and 8 controls (CTRs). Toluidine blue staining was used to observe morphological changes in sural nerves. The deposition of p-α-syn and p-tau was detected by immunohistochemistry with semiquantitative evaluation. Locations of p-α-syn and p-tau were identified by double immunofluorescent staining. In case groups, the density of nerve fibres decreased with swollen or fragmented Schwann cells (SCs). All cases (22/22) but no CTRs (0/8) presented p-α-syn immunoreactivity with gradually decreasing semiquantitative levels among the PD (6.00 ± 2.07), MSA (5.00 ± 2.33) and PSP (3.50 ± 1.52) groups. p-tau aggregates were found in 7/8 MSA (1.88 ± 1.46) and 6/6 PSP (1.67 ± 0.52) patients but not in PD patients or CTRs. There were different expression patterns of p-α-syn and p-tau in PD, MSA and PSP patients. These findings suggest that peripheral sensory nerve injury exists in PD, MSA and PSP patients. With a different expression pattern and level, p-α-syn and p-tau in sural nerves may serve as novel biomarkers for differential diagnosis of PD, MSA and PSP.


Asunto(s)
Atrofia de Múltiples Sistemas/diagnóstico , Enfermedad de Parkinson/diagnóstico , Parálisis Supranuclear Progresiva/diagnóstico , Nervio Sural/metabolismo , alfa-Sinucleína/metabolismo , Proteínas tau/metabolismo , Anciano , Biomarcadores/metabolismo , Diagnóstico Diferencial , Humanos , Persona de Mediana Edad , Atrofia de Múltiples Sistemas/metabolismo , Enfermedad de Parkinson/metabolismo , Fosforilación , Parálisis Supranuclear Progresiva/metabolismo
14.
Cell Death Discov ; 7(1): 14, 2021 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-33462196

RESUMEN

Hepatocellular carcinoma (HCC) is a globally prevailing cancer with a low 5-year survival rate. Little is known about its intricate gene expression profile. Single-cell RNA sequencing is an indispensable tool to explore the genetic characteristics of HCC at a more detailed level. In this study, we profiled the gene expression of single cells from human HCC tumor and para-tumor tissues using the Smart-seq 2 sequencing method. Based on differentially expressed genes, we identified heterogeneous subclones in HCC tissues, including five HCC and two hepatocyte subclones. We then carried out hub-gene co-network and functional annotations analysis followed pseudo-time analysis with regulated transcriptional factor co-networks to determine HCC cellular trajectory. We found that MLX interacting protein like (MLXIPL) was commonly upregulated in the single cells and tissues and associated with a poor survival rate in HCC. Mechanistically, MLXIPL activation is crucial for promoting cell proliferation and inhibits cell apoptosis by accelerating cell glycolysis. Taken together, our work identifies the heterogeneity of HCC subclones, and suggests MLXIPL might be a promising therapeutic target for HCC.

15.
Medicine (Baltimore) ; 99(33): e21736, 2020 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-32872060

RESUMEN

RATIONALE: Pilot studies have reported that patients with systemic lupus erythematosus (SLE) appear more likely to develop into neoplasia, especially lymphatic hyperplasia diseases. To our knowledge, this is the first case report of the concomitant onset of SLE and primary breast diffuse large B-cell lymphoma (PB-DLBCL). PATIENT CONCERNS: We reported an unusual case of the occurrence of primary breast diffuse large B-cell lymphoma in a 25-year-old female patient who had been diagnosed with SLE and treated with immunosuppressive drugs for about 4 years. She presented a 7-week history of a painless mass above the left breast and no history suggestive of any nipple discharge, fever, and weight loss. DIAGNOSIS: Ultrasonography of the breast showed that there was 1 mass in the left breast. After breast mass surgical resection, histopathological examinations were performed and revealed that it was primary breast diffuse large B-cell lymphoma. INTERVENTIONS: Treatment strategy with vincristine and dexamethasone was used to improve symptoms. However, the patient's renal function deteriorated and the blood potassium rose continuously and she and their family members refused the follow-up treatments. OUTCOMES: The patient died 8 months after she was discharged from the hospital. LESSONS: PB-DLBCL is a rare occurrence in SLE patients. Therefore, a careful examination is very important in SLE cohort, as activity of the disease and malignancy may mimic each other. Meanwhile, when symptoms cannot be explained or insensitive to treatment, the occurrence of malignant tumors must be highly considered.


Asunto(s)
Neoplasias de la Mama/complicaciones , Mama/patología , Fallo Renal Crónico/etiología , Lupus Eritematoso Sistémico/complicaciones , Linfoma de Células B Grandes Difuso/complicaciones , Adulto , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Resultado Fatal , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/terapia , Radiografía , Ultrasonografía
16.
Sensors (Basel) ; 20(9)2020 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-32397075

RESUMEN

The module of assimilating a new GMI (GPM Microwave Imager) satellite detector was built in the framework of the Weather Research and Forecasting Model (WRF) and its three-dimensional variational (3DVar) data assimilation system (WRFDA). Typhoon "Chan-Hom" in the 2015 Pacific typhoon season was selected to verify the effectivity of the GMI clear-sky assimilation. The results show that, after assimilating the GMI radiance data, the background information in the model is modified positively when compared with the experiment without any assimilation and the one with assimilation of the conventional data. The obvious warm core structure of the typhoon, the modified geopotential height field, and the intensified circulation of the typhoon are favorable for the northwest twist of the typhoon, thus contributing to a better track forecast with a maximum error below 160 km in the 48-h deterministic forecast.

17.
CNS Neurosci Ther ; 26(5): 518-526, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31828965

RESUMEN

AIMS: Neuroinflammation is one of the most important processes in the pathogenesis of Parkinson's disease (PD). Sensory disturbances are common in patients with PD, but the underlying pathophysiological mechanisms remain unknown. This study aimed to characterize the activation of Schwann cells (SCs) and the increase of expression of inflammatory cytokines IL-1ß, IL-6, and TNF-α in the sural nerve of PD, and further explore whether peripheral nerve inflammation is the cause of PD sensory disturbances. METHODS: A total of 14 patients with PD (including 5 with sensory disturbances and 9 without sensory disturbances) and 6 controls were included. The excitation and conduction function of sural nerve was detected by sural nerve electrophysiological examination. With sural nerve biopsy samples, ultrastructural changes of sural nerve were observed by electron microscopy; Schwann cell biomarker glial fibrillary acid protein (GFAP) and inflammatory cytokines including interleukin-1beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were detected by immunohistochemistry, and the outcome of immunostaining slice was semiquantitatively counted; double immunofluorescence was used to identify the locus immunoreactive for inflammatory cytokines. RESULTS: Compared with healthy controls, nerve conduction velocity (NCV) slowed down and sensory nerve action potential (SNAP) amplitude decreased in PD patients, accompanied by axonal degeneration and demyelinating lesions, and expression of GFAP and inflammatory cytokines was increased. Inflammatory cytokines were significantly colocalized with GFAP and slightly colocalized with NF. These indicators did not differ significantly between PD patients with and without sensory disturbances. CONCLUSION: Our study results suggest that peripheral sensory nerve injury exists in PD patients, accompanied by Schwann cell activation and inflammation, thus demonstrate peripheral nerve inflammation participates in the pathophysiological process of PD but it is not necessarily related to the patient's sensory disturbance.


Asunto(s)
Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Enfermedad de Parkinson/metabolismo , Células de Schwann/metabolismo , Nervio Sural/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Anciano , Citocinas/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conducción Nerviosa/fisiología , Enfermedad de Parkinson/patología , Células de Schwann/patología , Nervio Sural/patología
18.
Medicine (Baltimore) ; 98(36): e17048, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31490398

RESUMEN

RATIONALE: Cosmetic hyaluronic acid injections for facial soft tissue augmentation are gaining popularity because of their convenience and favorable outcomes. Several associated complications have been described; however, ophthalmic artery occlusion (OAO) combined with superior sagittal sinus thrombosis (SSST) has been rarely reported. PATIENT CONCERNS: A 21-year-old woman presented with sudden loss of vision and severe pain in the left eye, right upper limb weakness, and headache immediately after hyaluronic acid injection on the left side of her forehead. DIAGNOSIS: Clinical manifestations and multimodal imaging, including spectral-domain optical coherence tomography, fundus fluorescein angiography, and digital subtraction angiography, indicated OAO and SSST. INTERVENTIONS: Various clinical examinations were performed, and the patient was treated by thrombolysis, corticosteroids, oxygen therapy, a formula for the nourishment of the optic nerve, and measures for improving the microcirculation. OUTCOMES: The treatment response was closely observed. The intracerebral hemorrhages were absorbed after 2 weeks of treatment, while the clinical manifestations, including ocular pain, headache, and limb dysfunction, were gradually alleviated. However, the visual acuity in the left eye remained at no light perception. LESSONS: Cosmetic hyaluronic acid injection can result in emergent and catastrophic complications that require immediate treatment. Thus, the development of appropriate prevention and management protocols for such scenarios is considered crucial.


Asunto(s)
Arteriopatías Oclusivas/inducido químicamente , Ácido Hialurónico/efectos adversos , Arteria Oftálmica , Trombosis del Seno Sagital/inducido químicamente , Viscosuplementos/efectos adversos , Técnicas Cosméticas/efectos adversos , Femenino , Humanos , Inyecciones/efectos adversos , Adulto Joven
19.
J Pain Res ; 12: 1489-1495, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31190959

RESUMEN

Background and purpose: It has been generally thought that activation and sensitization of the trigeminovascular system may contribute to the pathogenesis of migraine. Nevertheless, there is little evidence on abnormalities in peripheral trigeminal afferent nerves from humans in vivo. Alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve may support the notion that trigeminal afferent nerves are involved in migraine pathophysiology. The aim of the present study was to investigate the structural changes in corneal subbasal nerve plexus in patients with episodic migraine (EM) with in vivo confocal microscope (IVCM). Methods: In this cross-sectional observational study, 10 EM patients and 10 age- and sex-matched healthy controls were included. Analysis of IVCM images with Image J software was performed to quantify the changes in the corneal subbasal nerve plexus. Results: EM patients showed an increase in nerve fiber length (25.0±2.65 vs 22.3±2.41 mm/mm2, p=0.047) and nerve fiber density (36.3±7.29 vs 30.5±6.19 fibers/mm2, p=0.104) as compared with normal controls, but this difference was not statistically significant. Nerve branching and tortuosity were significantly increased in the EM subjects compared to the normal subjects (91.3±13.8 vs 75.0±14.2 branches/mm2, p=0.030 and 2.30±0.46 versus 1.63±0.52, p=0.011, respectively). In addition, nerve sprouts and increased number of Langerhans cells were observed in the EM patients. Conclusion: The morphologic changes of corneal subbasal nerve plexus and Langerhans cell aggregation suggest the presence of nerve regeneration and inflammation in EM. Furthermore, the alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve offer support for the hypothesis that the peripheral trigeminal system may be involved in the pathogenesis of migraine.

20.
PeerJ ; 7: e6928, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31223522

RESUMEN

BACKGROUND AND AIMS: Recent evidence suggest that microbiota is associated with almost all major types of diseases, including cardiovascular diseases. However, its role in Acute Cerebral Infarction remains unexplored. It is important to understand the diversity and distribution of gut microbiota (GM) in patients with Acute Cerebral Infarction and the role that GM plays in this type of disease. METHODS: We performed pyrosequencing on the gut microbiota of 40 individuals in order to elucidate whether the composition of the microbiota differs between patients with Acute Cerebral Infarction and healthy controls: Of these individuals, there were 31 with Acute Cerebral Infarction and nine controls. We applied linear regression to calculate the correlation between the gut flora and disease risk factors. Finally, KEGG functional enrichment analysis was conducted to examine the correlation between the gut flora and Acute Cerebral Infarction. RESULTS: The overall microbial structure was similar in both the controls and the patients, but the control group had higher relative presence of Blautia obeum while the presence of Streptococcus infantis and Prevotella copri were relatively higher in the patient group. Using linear regression, we found that Blautia obeum was negatively associated with white blood cell count and Streptococcus infantis was positively correlated with creatinine and lipoprotein. The KEGG pathway analysis indicated that the bio-pathways including methane metabolism, lipopolysaccharide synthesis, bacterial secretion, and flagellar assembly of the gut microbiota in the patient group was expressed differently than that of the controls. We identified three differentially expressed gut microbial functions in Acute Cerebral Infarction and found four bacterial pathways that might be related to the development of this disease. CONCLUSIONS: Our study identified three abnormally-expressed bacteria-Blautia obeum, Streptococcus infantis, and Prevotella copri-in patients with Acute Cerebral Infarction compared with healthy controls. It reveals a correlation of these bacterial species with Acute Cerebral Infarction as they relate to disease factors and functional pathways. These findings may shed light on the treatment of cerebral infarction because gut microbiota could serve as a potential therapeutic approach for the treatment of cardiovascular and metabolic diseases.

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