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1.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1011104

RESUMO

Hyperlipidemia is characterized by elevated levels of blood lipids. The clinical manifestations are mainly atherosclerosis caused by the deposition of lipids in the vascular endothelium. The link between abnormal lipid metabolism and sudden hearing loss remains unclear. This article presents a case study of sudden hearing loss accompanied by familial hyperlipidemia. Pure tone audiometry indicated intermediate frequency hearing loss in one ear. Laboratory tests showed abnormal lipid metabolism, and genetic examination identified a heterozygous mutation in theAPOA5 gene. Diagnosis: Sudden hearing loss; hypercholesterolemia. The patient responded well to pharmacological treatment. This paper aims to analyze and discuss thepotential connection between abnormal lipid metabolism and sudden hearing loss.


Assuntos
Humanos , Audiometria de Tons Puros , Surdez/complicações , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Súbita/diagnóstico , Hiperlipidemias/complicações , Lipídeos
2.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1011096

RESUMO

Objective:To analyze genetic factors and phenotype characteristics in pediatric population with slight-to-moderate sensorineural hearing loss. Methods:Children with slight-to-moderate sensorineural hearing loss of and their parents, enrolled from the Chinese Deafness Genome Project, were studied. Hearing levels were assessed using pure tone audiometry, behavioral audiometry, auditory steady state response(ASSR), auditory brainstem response(ABR) thresholds, and deformed partial otoacoustic emission(DPOAE). Classification of hearing loss is according to the 2022 American College of Medical Genetics and Genomics(ACMG) Clinical Practice Guidelines for Hearing Loss. Whole exome sequencing(WES) and deafness gene Panel testing were performed on peripheral venous blood from probands and validations were performed on their parents by Sanger sequencing. Results:All 134 patients had childhood onset, exhibiting bilateral symmetrical slight-to-moderate sensorineural hearing loss, as indicated by audiological examinations. Of the 134 patients, 29(21.6%) had a family history of hearing loss, and the rest were sporadic patients. Genetic causative genes were identified in 66(49.3%) patients. A total of 11 causative genes were detected, of which GJB2 was causative in 34 cases(51.5%), STRC in 10 cases(15.1%), MPZL2 gene in six cases(9.1%), and USH2A in five cases(7.6%).The most common gene detected in slight-to-moderate hearing loss was GJB2, with c. 109G>A homozygous mutation found in 16 cases(47.1%) and c. 109G>A compound heterozygous mutation in 9 cases(26.5%). Conclusion:This study provides a crucial genetic theory reference for early screening and detection of mild to moderate hearing loss in children, highlighting the predominance of recessive inheritance and the significance of gene like GJB2, STRC, MPZL2, USH2A.


Assuntos
Humanos , Criança , Conexinas/genética , Conexina 26/genética , Perda Auditiva Neurossensorial/diagnóstico , Mutação , Síndromes de Usher , Perda Auditiva Bilateral , Audiometria de Tons Puros , Peptídeos e Proteínas de Sinalização Intercelular
3.
Chinese Journal of Pathology ; (12): 153-159, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-970150

RESUMO

Objective: To investigate the pathological features and the clinicopathological significance of TERT detection in those tumors that were difficult to diagnosis. Methods: A total of 93 cases of fibroepithelial tumors without definite diagnosis were collected from the Affiliated Hospital of Qigndao University between 2013 and 2021. The clinical details such as patients' age and tumor size were collected. All slides were re-reviewed and the pathologic parameters, including stromal cellularity, stromal cell atypia, stromal cell mitoses, and stromal overgrowth were re-interpreted. Sanger sequencing was used to detect TERT promoter status, and immunohistochemistry was performed to detect TERT protein expression. The relationship between TERT promoter mutation as well as protein expression levels and the clinicopathological parameters were also analyzed. Results: The patients' ages ranged from 30 to 71 years (mean of 46 years); the tumor size ranged from 1.2 to 8.0 cm (mean 3.8 cm). These tumors showed the following morphologic features: leafy structures in the background of fibroadenoma, or moderately to severely abundant stromal cells. The interpretations of tumor border status were ambiguous in some cases. The incidence of TERT promoter mutation was high in patients of age≥50 years, tumor size≥4 cm, and stromal overgrowth at ×4 or ×10 objective, and these clinicopathologic features were in favor of diagnosis of phyllodes tumors. TERT protein expression levels was not associated with the above clinicopathologic parameters and its promoter mutation status. Conclusions: The diagnostic difficulty for the breast fibroepithelial tumors is due to the difficulty in recognition of the leafy structures or in those cases with abundant stromal cells. A comprehensive evaluation combined with morphologic characteristics and molecular parameters such as TERT promoter may be helpful for the correct diagnosis and better evaluating recurrence risk.


Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Neoplasias Fibroepiteliais/patologia , Tumor Filoide/genética , Células Estromais , Fibroadenoma/patologia , Neoplasias da Mama/patologia , Mutação , Telomerase/genética
4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-990044

RESUMO

Objective:To explore risk factors for clinical onset in children with uncontrolled self-limited epilepsy with centrotemporal spikes (SeLECTS) managed by 2 anti-seizure medications (ASMs).Methods:A total of 112 children with SeLECTS who were diagnosed at the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University from January 2018 to May 2021 were retrospectively reviewed.All of them were treated with conventional ASMs, and regularly followed up for 1-2 years.Types of therapeutic drugs, clinical seizure control status, presence of new seizure forms, electroencephalogram (EEG) were reviewed at follow-up visits.According to whether the seizures were controlled after the use of no more than 2 ASMs, patients were divided into poor response group (43 cases) and good response group (69 cases), and their clinical data and EEG characteristics were compared.Multivariate Logistic regression analysis was used to explore the risk factors for seizures that were uncontrolled by 2 ASMs. Results:There were significant differences in the age of onset ( χ2=8.919, P=0.003), seizure form ( χ2=4.218, P=0.040), seizure frequency ( Z=-7.664, P<0.001), EEG background slowing ( χ2=10.284, P=0.001), emergence of electrical status epilepticus during slow-wave sleep (ESES)( χ2=11.921, P=0.001), discharge generalization ( χ2=25.377, P<0.001), and presence of epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS)( χ2=54.334, P<0.001) between groups.Multivariate Logistic regression analysis showed that seizure frequency ( P<0.001, OR=0.086, 95% CI: 0.022-0.329), discharge generalization ( P=0.006, OR=9.942, 95% CI: 1.918-51.527) and EEG background slowing ( P=0.041, OR=6.648, 95% CI: 1.077-41.038) were the 3 main risk factors associated with poor response to short-term medications of ASMs. Conclusions:Seizures are easily controlled in most SeLECTS patients medicated with ASMs with a favorable prognosis.Seizure frequency, discharge generalization and EEG background slowing are risk factors for the poor response to short-term pharmacotherapy in children with SeLECTS.

5.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-971478

RESUMO

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.


Assuntos
Humanos , Fator de Indução de Apoptose/metabolismo , NAD/metabolismo , Dimerização , Apoptose
6.
Urolithiasis ; 50(5): 545-556, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35913552

RESUMO

Calcium oxalate (CaOx) crystals can activate autophagy, causing damage to renal tubular epithelial cells (TECs). Puerarin has been shown to have protective and therapeutic effects against a variety of diseases by inhibiting autophagy activation. However, the protective effect of puerarin against CaOx crystals and the underlying molecular mechanisms are unclear. Cell Counting Kit-8 (CCK-8) assays were used to evaluate the effects of puerarin on cell viability. Intracellular reactive oxygen species (ROS) levels were measured by the cell-permeable fluorogenic probe 2,7-dichlorofluorescein diacetate (DCFH-DA). Immunofluorescence, immunohistochemistry, and western blotting were used to examine the expression of SIRT1, Beclin1, p62, and LC3, and explore the underlying molecular mechanisms in vivo and in vitro. Puerarin treatment significantly attenuated CaOx crystal-induced autophagy of TECs and CaOx cytotoxicity to TECs by altering SIRT1 expression in vitro and in vivo, whereas the SIRT1-specific inhibitor EX527 exerted contrasting effects. In addition, we found that the protective effect of puerarin was related to the SIRT1/AKT/p38 signaling pathway. The findings suggest that puerarin regulates CaOx crystal-induced autophagy by activating the SIRT1-mediated signaling pathway, and they suggest a series of potential therapeutic targets and strategies for treating nephrolithiasis.


Assuntos
Oxalato de Cálcio , Cálculos Renais , Autofagia , Oxalato de Cálcio/metabolismo , Células Epiteliais/metabolismo , Humanos , Isoflavonas , Cálculos Renais/metabolismo , Estresse Oxidativo , Transdução de Sinais , Sirtuína 1/metabolismo , Sirtuína 1/farmacologia
8.
Acta Pharmaceutica Sinica ; (12): 2342-2351, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-937037

RESUMO

Previously, we discovered that cells contain a 5-hydroxytryptamine (5-HT) degradation system (5DS), which includes 5-HT2A receptor (5-HT2AR), 5-HT synthase, and monoamine oxidase A (MAO-A). Among these, 5-HT2AR has the ability to regulate the expression of 5-HT synthase and MAO-A, and activation of 5DS causes upregulation of these proteins at the same time, resulting in the production of reactive oxygen species (ROS) in the mitochondria. In this study, we investigated the relationship between interstitial pneumonia (IP) and 5DS activation, as well as the therapeutic effect of inhibiting 5DS on IP. Animal models of bleomycin (BLM)-induced IP in mice and radiation (Rad)-induced IP in rats were established, and the models were treated with the 5-HT2AR antagonist sarpogrelate hydrochloride (SH), 5-HT synthesis inhibitor carbidopa (CDP), and their combination (SH∶CDP = 2∶1). The animal experiments were carried out in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University. In the two IP models, immunohistochemistry staining and Western blot analysis showed that the expression of 5-HT synthase was significantly upregulated in all cells of lung tissue, while the expression of 5-HT2AR and MAO-A was most significantly upregulated in the macrophages. Treatment with SH or CDP significantly reduced pulmonary interstitial thickening, alveolar atrophy with collapse, massive macrophage infiltration and interstitial fibrosis in the two IP models, as measured by HE and Masson staining, and a combination of both almost eliminated the lung tissue lesions. Moreover, treatment with the combination of SH and CDP almost completely eliminated increased ROS and malondialdehyde levels, decreased superoxide dismutase activity, increased tumor necrosis factor-α and interleukin-1β levels, and upregulated nuclear factor-κB phosphorylation and α‍-smooth muscle actin, matrix metalloproteinase-2, and collagen expression. SH and CDP worked together to create a synergistic effect. The findings suggested that the activation of 5DS, as evidenced by increased 5-HT synthesis in all cells of lung tissue and increased 5-HT synthesis and degradation in macrophages, is probably related to the occurrence of IP and that inhibition of 5DS can effectively treat IP.

9.
Chinese Journal of Pediatrics ; (12): 51-55, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-935639

RESUMO

Objective: To explore the clinical manifestations and genetic characteristics of patients with epilepsy and episodic ataxia caused by SCN2A gene variation. Methods: The clinical data of seizure manifestation, imaging examination and genetic results of 5 patients with epilepsy and (or) episodic ataxia because of SCN2A gene variation admitted to the Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University from July 2017 to January 2021 were analyzed retrospectively. Results: Among 5 patients, 4 were female and 1 was male. The onset age of epilepsy ranged from 4 days to 8 months. There were 2 cases of benign neonatal or infantile epilepsy and 3 cases of epileptic encephalopathy, in whom 1 case had development retardation,1 case transformed from West syndrome to infantile spasm and another one transformed from infantile spasm to Lennox-Gastaut syndrome. One case of benign neonatal-infantile epilepsy was characterized by neonatal onset seizures and episodic ataxia developed at the age of 78 months. Electroencephalograms at first visit of 5 cases showed that 2 cases were normal, 1 case had focal epileptic discharge, and 2 cases had multi-focal abnormal discharge with peak arrhythmia. The brain magnetic resonance imaging (MRI) of 3 cases were nomal, 1 case was abnormal (brain atrophy with decreased white matter) and the results of 1 case was unknown. The follow-up time ranged from 17 months to 89 months. Four cases of epilepsy were controlled and 1 case died at 2 years of age. Two cases had normal intelligence and motor development, 2 had moderate to severe intelligence retardation and motor critical state, and 1 had moderate to severe intelligence and motor development retardation. SCN2A gene variations were identified in all cases. There were 4 missense variations and 1 frameshift variation. Three variations had not been reported so far, including c.4906A>G,c.3643G>T,c.638delT. Conclusions: Variations in SCN2A gene can cause benign neonatal or infantile epilepsy and epileptic encephalopathy. Some children develop episodic ataxia with growing age. The variation of SCN2A gene is mainly missense variation.


Assuntos
Criança , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Ataxia/genética , Eletroencefalografia , Epilepsia/genética , Mutação , /genética , Estudos Retrospectivos , Espasmos Infantis/genética
10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-928417

RESUMO

As a male-specific chromosome, the structure of Y chromosome is complex and lacks of recombination, with numerous repeating, amplifying and palindromic sequences. The research of Y chromosome is difficult and slow since there are few protein coding genes and a large amount of heterochromatin which has caused extreme difficulty for sequencing. In recent years, an increasing number of studies have been focused on the Y chromosome. With the completion of the sequencing of human Y chromosome, the rapid development of sequencing technology, and the composition of DNA sequences in human Y chromosomes and the determination of gene content. This paper has summarized the structural composition and genes function of human Y chromosome, as well as the related hereditary diseases, with an aim to provide reference for Y chromosome-related genetic research.


Assuntos
Humanos , Masculino , Cromossomos Humanos Y/genética
11.
J BUON ; 26(3): 830-836, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268942

RESUMO

PURPOSE: We aimed to investigate the efficacy and safety of zoledronic acid combined with chemotherapy in treating non-small cell lung cancer (NSCLC) with bone metastasis. METHODS: The clinical data of 148 NSCLC patients with bone metastasis were retrospectively analyzed. Among the patients, 74 were treated with zoledronic acid combined with chemotherapy (Zoledronic Acid group), while the remaining 74 received chemotherapy alone (Control group). The efficacy on bone metastasis, remission of bone pain, levels of bone metabolic markers before and after treatment, quality of life and incidence rate of adverse reactions were compared between the two groups. Besides, the patients were followed up, and their survival status was recorded. RESULTS: The efficacy was evaluated in all patients at 1 month after treatment. It was found that the overall response rate of bone metastasis was significantly higher in the Zoledronic Acid group than that in the Control group. After treatment, the ostealgia remission rate was markedly higher in the Zoledronic Acid group than that in the Control group. After treatment, the serum levels of alkaline phosphatase (AKP), Ca2+, N-terminal telopeptide (NTx) and bone sialoprotein (BSP) declined notably in both groups in contrast with those before treatment, and they were prominently lower in the Zoledronic Acid group than those in the Control group after treatment. Moreover, after treatment, the Karnofski performance status (KPS) score was improved in both groups, and the Zoledronic Acid group had an evidently higher score than the Control group. The results of follow-up manifested that the 1-, 2- and 3-year overall survival (OS) rates in the Zoledronic Acid group and the Control group were 58.1% (43/74) vs. 43.2% (32/74), 40.5% (30/74) vs. 29.7% (22/74), and 24.3% (18/74) vs. 13.5% (10/74), respectively. Log-rank test revealed that the OS in the Zoledronic Acid group was significantly better than that in the Control group. CONCLUSION: Zoledronic acid combined with chemotherapy is effective in the treatment of NSCLC with bone metastasis, which can markedly relieve bone pain, ameliorate the quality of life of patients, improve the long-term survival rate and reduce the incidence of SREs.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Ácido Zoledrônico/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Ácido Zoledrônico/efeitos adversos
12.
Chinese Journal of Digestion ; (12): 665-670, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-912222

RESUMO

Objective:To explore the serum levels of copper and zinc and the application value of the ratio in assessing disease activity in patients with inflammatory bowel disease (IBD).Methods:From March 2019 to April 2020, 200 patients with IBD hospitalized at the Department of Gastroenterology of the First Affiliated Hospital of Anhui Medical University were selected by prospective random direct sampling method, including 100 patients with Crohn′s disease (CD) and 100 patients with ulcerative colitis (UC). The Crohn′s disease activity index (CDAI) and the modified Mayo score were used to evaluate the disease activity of CD patients and UC patients. In the same period 100 healthy individuals in the routine physical examination were selected as healthy control group. The serum levels of copper and zinc of the healthy control group, the CD group and the UC group were determined by atomic absorption spectrometry. The levels and the ratio of serum copper to zinc of three groups were compared. The ratio of serum copper to zinc of CD patients and UC patients with different disease activity were compared. The correlation between the ratio of serum copper to zinc and IBD activity indexes were analyzed, which included fecal calprotectin (FC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), CDAI and Mayo score. Receiver operating characteristic curve was drawn to analyze the value of the ratio of serum copper to zinc, CRP and ESR in predicting disease activity of patients with IBD. Independent sample t test, least significant difference- t test and Pearson correlation analysis were performed for statistical analysis. Results:The serum copper levels and the ratio of serum copper to zinc of the CD group and the UC group were both higher than that of the healthy control group, however the serum zinc levels were lower than that of the healthy control group ( (32.27±7.69) and (29.80±9.68) mol/L vs. (20.16±6.67) mol/L; 2.81±1.57 and 2.29±1.09 vs. 0.68±0.36; (14.64±7.11) and (15.65±8.17) mol/L vs. (34.29±16.40) mol/L), and the differences were statistically significant ( t=2.81, 5.87, 1.47, 7.21, 1.73 and 2.56, all P<0.05). Among CD patients, the the ratio of serum copper to zinc of patients at remission stage (29 cases), mild activity stage (23 cases), moderate activity stage (30 cases) and severe activity stage (18 cases) was 2.61±1.43, 2.75±1.35, 3.15±2.37 and 4.17±1.77, respectively, and the ratios of serum copper to zinc of patients at mild activity stage, moderate activity stage and severe activity stage were all higher than that of patients at the remission stage, and the differences were statistically significant ( t=3.41, 7.92 and 5.84, all P<0.05). There were statistically significant differences in the ratios of serum copper to zinc between patients at mild activity stage and moderate activity stage, severe activity stage, and between patients at moderate activity stage and severe activity stage ( t=5.82, 6.23 and 3.45, all P<0.05). Among UC patients, the ratio of serum copper to zinc of patients at remission stage (10 cases), mild activity stage (30 cases), moderate activity stage (45 cases) and severe activity stage (15 cases) was 1.52±0.44, 1.74±0.58, 2.38±0.83 and 3.80±1.19, respectively, the ratio of serum copper to zinc of patients at moderate activity stage was higher than that of patients at remission stage and mild activity stage, and the ratio of serum copper to zinc of patients at severe activity stage was higher than those of patients at remission stage, mild activity stage and moderate activity stage, and the differences were statistically significant ( t=7.92, 5.83, 3.21, 9.54 and 2.83, all P<0.05). There was no statistically significant difference in serum copper to zinc ratio between patients at remission and at mild activity stage ( P>0.05). The ratio of serum copper to zinc of CD patients was positively correlated with FC and CRP ( r=0.697 and 0.586, P=0.014 and 0.001), however was not correlated with ESR or CDAI score (both P>0.05). The ratio of serum copper to zinc of UC patients was positively correlated with FC, ESR and Mayo score ( r=0.488, 0.452 and 0.331, P=0.001, P<0.01 and P=0.041), however was not correlated with CRP ( P>0.05). The cut-off value of the ratio of serum copper to zinc, CRP and ESR for the diagnosis of CD activity was 1.76, 8 mg/L and 20 mm/1 h, respectively. Among them, ESR was the most effective in the diagnosis of CD activity with an area under the curve (AUC) value of 0.830, and to the sensitivity and specificity was 69.0% and 86.2%, respectively. The cut-off value of the ratio of serum copper to zinc, CRP and ESR for the diagnosis of UC activity was 1.63, 8 mg/L and 20 mm/1 h, respectively; among which the the ratio of serum copper to zinc had the highest efficacy in the diagnosis of UC activity, with an AUC value of 0.862, sensitivity and specificity of 73.0% and 90.9%, respectively. Conclusion:The the ratio of serum copper to zinc is correlated with the disease activity of IBD, which may become a new auxiliary indicator for the evaluation of disease activity.

13.
Acta Pharmaceutica Sinica ; (12): 1612-1620, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-881562

RESUMO

Hyperglycemic kidney injury (HKI) is a common complication of diabetic patients. We examined the relationship between HKI and the abnormal expression of 5-hydroxytryptamine (5-HT) system induced by hyperglycemia in type 2 diabetes mellitus (T2DM). In animal experiments, a T2DM model was established in mice by feeding a high-fat diet with intraperitoneal injection of streptozotocin. The mice were treated with the 5-HT2A receptor (5-HT2AR) antagonist sarpogrelate hydrochloride (SH) and 5-HT synthesis inhibitor carbidopa (CDP) (respectively or in combination). In cell culture experiments, human glomerular mesangial cells (HMC) were stimulated with D-glucose (D-Glu), and 5-HT2AR, 5-HT synthesis, and 5-HT degradation were inhibited by SH, CDP, or monoamine oxidase A (MAO-A) inhibitor clorgyline. Periodic acid-Schiff (PAS) staining and Masson staining, immunohistochemistry and Western blot, fluorescent probe, and enzyme linked immunosorbent assay (ELISA) and enzyme reagent were respectively used to detect histopathology, protein expression, intracellular reactive oxygen species (ROS), and biochemical indexes. The animal experiments were in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University. The results showed that 5-HT2AR, 5-HT synthases, and MAO-A were expressed in glomerular basement membrane and kidney tubular epithelial cells of mouse kidney and HMC. The expression of these proteins was significantly up-regulated in T2DM mice or when HMC cells were exposed to high concentration of D-Glu. HKI, characterized by abnormal renal function, glomerular swelling, and glomerular basement membrane thickening and fibrosis, is closely associated with an increase in kidney 5-HT2AR, 5-HT synthesis, and 5-HT degradation. Among them, 5-HT2AR can mediate the expression of 5-HT synthases and MAO-A; MAO-A can catalyze the degradation of 5-HT to increase the production of mitochondrial ROS, leading to the phosphorylation of nuclear factor kappa B (NF-κB) with the production of inflammatory cytokines, and the up-regulation of matrix metalloproteinase-2 (MMP-2) and α-smooth muscle actin (α-SMA) with the production of collagens. SH and CDP can effectively treat HKI, and the combination of SH and CDP has a clear synergistic effect.

14.
Acta Pharmaceutica Sinica ; (12): 190-200, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-872624

RESUMO

Fatigue is a common complication of type 2 diabetes mellitus (T2DM). We examined the relationship between T2DM fatigue and the skeletal muscle 5-hydroxytryptamine (5-HT) system. In animal experiments, a T2DM model was established in mice by feeding a high-fat diet with intraperitoneal injection of streptozotocin. The mice were treated with the 5-HT2A receptor antagonist sarpogrelate hydrochloride (SH) and the 5-HT synthesis inhibitor carbidopa (CDP) (separately and in combination). In cell culture experiments, C2C12 cells were stimulated with D-glucose, palmitic acid or 5-HT. 5-HT2AR, 5-HT synthesis and 5-HT degradation were inhibited by SH, CDP, or monoamine oxidase A (MAO-A) inhibitor. The animal experiments were in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University. The results showed that 5-HT2AR, 5-HT synthase and MAO-A were expressed in mouse skeletal muscle and C2C12 cells. The expression of these proteins was significantly up-regulated in T2DM mice or when C2C12 cells were exposed to palmitic acid and D-glucose; palmitic acid was a stronger stimulant of their expression than D-glucose. Rotating rod experiments and biochemical index tests have shown that T2DM fatigue is associated with an increase in skeletal muscle 5-HT2AR, 5-HT synthesis and 5-HT degradation. 5-HT2AR mediates the expression of MAO-A and the synthesis of 5-HT, which indirectly regulates the degradation of 5-HT. MAO-A regulates cell inflammation, mitochondrial ROS production and membrane potential depolarization by mediating 5-HT degradation. MAO-A also inhibits the expression of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1), carnitine palmitoyltransferase-1 (CPT1) and ATP synthase-6 (ATP6), thus inhibiting mitochondrial functions such as fatty acid β oxidation and ATP synthesis. SH and CDP can effectively treat T2DM fatigue, and can also reduce blood glucose and blood lipid, and the combination of SH and CDP has a clear synergistic effect.

15.
Zhongguo Zhong Yao Za Zhi ; 45(18): 4373-4381, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33164365

RESUMO

Comparison of total organic carbon(TOC), total nitrogen(TN), total phosphorus(TP), soil microbial biomass carbon(MBC), nitrogen(MBN), phosphorus(MBP) and their stoichiometric ratios measuring from understory planting of Paris polyphylla and Panax japonicus rhizosphere soil with the data of the original forest soil will help us to understand the influence of different planting patterns between soil traits and soil microbial interaction and nutrient cycle characteristics. The results showed that the contents of TOC, TN and MBN were the highest in the rhizosphere soil of P. japonicus, while the highest values of TP, MBC and MBP were found in the rhizosphere soil of P. polyphylla. The changes of TOC∶TN, TOC∶TP, TN∶TP, MBC∶MBN, MBC∶MBP and MBN∶MBP of P. polyphylla and P. japonicus rhizosphere soil compared with the data of the original forest soil were 3.65 and 37.32%,-14.89 and 82.23%,-17.87 and 32.76%, 25.67 and-50.60%,-75.95 and-16.33% as well as-80.79 and 69.76%, respectively. TN and TP were significantly correlated with MBN and MBP respectively. Although, monoculture of P. polyphylla and P. japonicus changed soil nutrient level, it did not reach the state of nutrient deficiency. The demands for nitrogen and phosphorus between P. polyphylla and P. japonicus were quite different. According to their different habits, monoculture of P. polyphylla and P. japonicus could change the understory soil traits, resulting in allometric changes in part of soil nutrient stoichiometry and soil microbial stoichiometry, and then the disappearance of internal stability. The variations in the understory soil caused by P. polyphylla and P. japonicus is developing in completely different directions, whether this phenomenon indicates that the two species have less niche overlap needs further study.


Assuntos
Liliaceae , Panax , Biomassa , Carbono , China , Nitrogênio/análise , Fósforo/análise , Rizosfera , Solo , Microbiologia do Solo
16.
Exp Ther Med ; 20(5): 98, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32973947

RESUMO

Diagnosing epilepsy at the early stages is pivotal in the prevention and subsequent treatment of major epileptic events. MRI has been previously demonstrated to be beneficial in optimizing diagnostic efficacy and the subsequent treatment of epilepsy. In the present study, morphometric and textural analysis was performed pre-operatively on dynamic contrast-enhanced (Dce)-magnetic resonance imaging (MRI)-guided lesions in patients with epilepsy. The diagnostic efficacies of MRI and Dce-MRI were evaluated in 280 patients with epilepsy. The performance of Dce-MRI (n=140) was compared with that of classic MRI (n=140) in the analysis of the morphometric and textural features of the lesions, and the accuracy of mapping to regions of the brain that were potentially associated with the region of seizure onset was also investigated. Diagnostic quality was evaluated by comparing the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the hippocampus, the grey-white matter contrast and the morphometric and textural analysis of epileptogenic lesions. Data from the present study demonstrated that the regions of suspected epileptic activity in the brain were mapped more successfully using Dce-MRI compared with MRI. Image quality obtained by Dce-MRI was adequate for the detection of epileptic lesions, including those of focal cortical dysplasia or periventricular nodular heterotopia (PNH). The diagnostic value of Dce-MRI for subtle lesions such as PNH was found to be more efficient compared with that of MRI due to the significantly increased SNR and CNR. In addition, Dce-MRI exhibited higher accuracy compared with MRI for the identification of cortical lesions and for the mapping to the zone of suspected seizure onset. Dce-MRI also exhibited higher sensitivity and specificity in the diagnosis of patients with epilepsy and mapping to the lesions associated with epilepsy compared with MRI. These findings indicate that Dce-MRI is a feasible technique that may be beneficial in the diagnosis and subsequent management of patients with epilepsy.

17.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-827385

RESUMO

OBJECTIVES@#To analyze the clinical characteristics of fecal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid-positive in patients with coronavirus dasease 2019 (COVID-19) and to provide a scientific basis for the prevention and control of this disease.@*METHODS@#The clinical data of 16 patients with fecal SARS-CoV-2 nucleic acid positive, who hospitalized in the North Branch of the First Hospital of Changsha (Changsha Public Health Rescue Center) from January to February 2020, were retrospectively analyzed. Their clinical manifestations, laboratory data and imaging data were summarized.@*RESULTS@#Among the 16 patients, there were 9 males (56.25%) and 7 females (43.75%), the ratio of males to females was 1∶1.29. The age of onset was (43.3±14.6) years. There were 15 patients with contact history of Wuhan, 1 patient with contact history of local patient.Twelve patients were common type (75%), and 4 patients were severe type (25%). Clinical symptoms included fever in 14 patients (87.5%), cough in 12 patients (75%), shortness of breath in 5 patients (31.25%), pharyngalgia in 10 patients (62.5%), fatigue in 7 patients (43.75%), and diarrhea in 4 patients (25%). There were 14 patients (87.5%) with normal or decreased white blood cell count, 11 patients (68.75%) with decreased lymphocyte count, 15 patients (93.75%) with increased erythrocyte sedimentation rate, 13 patients (81.25%) with increased hypersensitivity C-reactive protein, 5 patients (31.25%) with increased procalcitonin, and 8 patients (50%) with increased serum ferritin in peripheral blood, and stool routine was basically normal. Compared with the common type, there was significant difference in the white blood cell and lymphocyte counts in the severe type (0.05). Chest CT mainly showed patchy shadows and interstitial changes. According to imaging examination, 4 patients (25%) showed unilateral pneumonia and 12 patients (75%) showed bilateral pneumonia.@*CONCLUSIONS@#The patients have the clinical symptoms of COVID-19, but gastrointestinal symptoms (such as diarrhea) are more common, and the changes of white blood cell count, lymphocyte count, hypersensitivity C-reactive protein, ferritin are more obvious in severe patients.The positivity of fecal nucleic acid suggests the possibility of digestive tract transmission of SARS-CoV-2, and fecal nucleic acid testing can be used as a routine testing method in clinical practice.


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Betacoronavirus , Proteína C-Reativa , China , Infecções por Coronavirus , Diagnóstico , Diarreia , Virologia , Fezes , Virologia , Ferritinas , Contagem de Leucócitos , Pandemias , Pneumonia Viral , Diagnóstico , Estudos Retrospectivos
18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-821516

RESUMO

Objective@#The aim of this study was to explore the clinical features, hearing prognosis and differential diagnosis of recurrent low frequency sensorineural hearing loss (RLFD) . @*Method@#The clinical characteristics, clinical manifestations, audiological examination and auxiliary examination of RLFD patients were retrospectively analyzed. We summarized clinical features, draw the pure tone audiometry curves, and analyze the diagnosis of RLFD. @*Result@#Forty-seven patients (53 ears) with RLFD had a hearing review time of 1-124 months. The course of disease ranged from 3 to 320 months with an average course of 29 months. ①The incidence of tinnitus in the accompanying symptoms was 93.6%(44 cases), and the ear suffocation was 83.0%(39 cases), 38.3% (18 cases) of the patients developed vestibular symptoms during the course of the disease. ②During the observation period, 27 cases(57.4%) were diagnosed with related diseases: 7 cases(14.9%) Meniere's disease, 6 cases(12.8%) vestibular migraine, 2 cases(4.3%) with Meniere's disease and migraine, and 1 case(2.1%) with idiopathic intracranial hypotension 11 cases(23.4%) were possible cochlear migraine; ③Migraine-related RLFD had a younger onset age, more common in women; ④83.0%(44 ears)of the affected ears had stable or improved low-frequency hearing during the observation period, 17.0%(9 ears)of the affected ears experienced low-frequency hearing; ⑤18.9%(10 ears)of the affected ears had high-frequency hearing loss; ⑥RLFD had 6 types of audiological outcomes: low-frequency improvement combined with high-frequency stability; low-frequency stability combined with high-frequency stability; low frequency progress combined with high frequency stability type; low frequency improvement combined with high frequency progress type; low frequency stability combined with high frequency progress type; low frequency progress combined with high frequency progress type; ⑦Rising type hearing curve low frequency hearing prognosis is good, mountain type and descending low frequency hearing prognosis is poor. @*Conclusion@#Tinnitus and ear stuffiness are the early symptoms and the most disturbing symptoms in patients with RLFD. The mechanism of Migraine may play an important role in the pathogenesis of RLFD. The rare causes such as intracranial hypotension syndrome should not be ignored. Most of the patients with RLFD had stable or improved hearing after long-term fluctuation, but some patients with low or high frequency hearing might decline. The type of initial hearing curve was a prognostic factor. Long-term hearing follow-up is helpful for prognosis evaluation.

19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-867059

RESUMO

Objective:To explore the effects of miR-301a-3p on proliferation and apoptosis of astrocytes in rats.Methods:miR-301a-3p agomir and miR-301a-3p antagomir were synthetized and transfected into astrocytes. The cells were divided into Blank group, miR-NC group, miR-301a agomir group and antagomir group.Each group has 3 multiple pores, 2×10 5 cells per pore. CCK8 method was used to detect proliferation and growth ability of astrocytes in each group. Anncxin V-FITC/PI cytometry and Caspase-3 were used to test apoptosis of cells in each group. Results:Compared with Blank group (48 h: 0.83±0.09; 72 h: 1.20±0.21; 96 h: 1.65±0.17) and miR-NC group (48 h: 0.79±0.10; 72 h: 1.12±0.25; 96 h: 1.60±0.15), the proliferation ability of miR-301a group (48 h: 1.16±0.07; 72 h: 1.56±0.11; 96 h: 2.13±0.14) was significantly improved ( P<0.05), and the apoptosis rate of miR-301a group decreased significantly (Blank group: 10.44±1.33, miR-NC group: 9.84±1.40, miR-301a group: 4.32±0.51, P<0.05). Compared with Blank group and miR-NC group, the proliferation ability of the cells in antagomir group (48 h: 0.52±0.12; 72 h: 0.72±0.09; 96 h: 1.01±0.15) decreased significantly ( P<0.05), and the apoptotic rate was significantly increased in the antiagor group (Blank group: 10.44±1.33, miR-NC group: 9.84±1.40, antiagor group: 21.41±2.57, P<0.05). Conclusion:miRNA-301a-3p hyperexpression can promote the proliferation of astrocytes and inhibit the apoptosis pathway, thereby regulating the biological function of rat astrocytes.

20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-787734

RESUMO

The aim of this study was to explore the clinical features, hearing prognosis and differential diagnosis of recurrent low frequency sensorineural hearing loss (RLFD) . The clinical characteristics, clinical manifestations, audiological examination and auxiliary examination of RLFD patients were retrospectively analyzed. We summarized clinical features, draw the pure tone audiometry curves, and analyze the diagnosis of RLFD. Forty-seven patients (53 ears) with RLFD had a hearing review time of 1-124 months. The course of disease ranged from 3 to 320 months with an average course of 29 months. ①The incidence of tinnitus in the accompanying symptoms was 93.6%(44 cases), and the ear suffocation was 83.0%(39 cases), 38.3% (18 cases) of the patients developed vestibular symptoms during the course of the disease. ②During the observation period, 27 cases(57.4%) were diagnosed with related diseases: 7 cases(14.9%) Meniere's disease, 6 cases(12.8%) vestibular migraine, 2 cases(4.3%) with Meniere's disease and migraine, and 1 case(2.1%) with idiopathic intracranial hypotension 11 cases(23.4%) were possible cochlear migraine; ③Migraine-related RLFD had a younger onset age, more common in women; ④83.0%(44 ears)of the affected ears had stable or improved low-frequency hearing during the observation period, 17.0%(9 ears)of the affected ears experienced low-frequency hearing; ⑤18.9%(10 ears)of the affected ears had high-frequency hearing loss; ⑥RLFD had 6 types of audiological outcomes: low-frequency improvement combined with high-frequency stability; low-frequency stability combined with high-frequency stability; low frequency progress combined with high frequency stability type; low frequency improvement combined with high frequency progress type; low frequency stability combined with high frequency progress type; low frequency progress combined with high frequency progress type; ⑦Rising type hearing curve low frequency hearing prognosis is good, mountain type and descending low frequency hearing prognosis is poor. Tinnitus and ear stuffiness are the early symptoms and the most disturbing symptoms in patients with RLFD. The mechanism of Migraine may play an important role in the pathogenesis of RLFD. The rare causes such as intracranial hypotension syndrome should not be ignored. Most of the patients with RLFD had stable or improved hearing after long-term fluctuation, but some patients with low or high frequency hearing might decline. The type of initial hearing curve was a prognostic factor. Long-term hearing follow-up is helpful for prognosis evaluation.

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