RESUMO
Objective: To compare the diagnostic performance of next-generation sequencing (NGS) detection methods in sputum samples and Mycobacterium tuberculosis strains, in order to explore the feasibility of the NGS method to detect drug resistance in sputum specimens. Methods: In this retrospective study, the sputum specimens and corresponding clinical isolates of 50 pulmonary tuberculosis patients admitted to Beijing Chest Hospital from January 2017 to December 2017 were collected. The gene mutations of katG, inhA, rpoB, embA, embB, rpsL, rrs, gyrA, gyrB and tlyA in sputum specimens and corresponding clinical isolates were detected by NGS method. The phenotypic drug susceptibility test (DST) of the strains was carried out by the proportion method. Using DST results as a reference, the sensitivity, specificity, positive predictive value and negative predictive value of the NGS method for clinical strains and sputum specimens, as well as the consistency statistic (Kappa) with phenotype DST were calculated respectively. The Chi-square test was used to compare the accuracy of the NGS testing in sputum samples and strain samples. Results: The results showed that rpoB(63.83%, 30/47) and rrs(57.45%, 27/47) were the most common mutated genes, followed by katG(46.81%, 22/47), rpsL(29.79%, 14/47), gyrA(27.66%, 13/47), embB(21.28%, 10/47), tlyA(12.77%, 6/47), gyrB(8.51%, 4/47), and inhA promoter(19.15%, 9/47), embA promoter region (12.77%, 6/47) mutation. when the NGS method was compared with the resistance phenotype of isoniazid, rifampicin, ethambutol, second-line injectable drugs (streptomycin, capreomycin, kanamycin, amikacin), levofloxacin, the sensitivity were 85.71%, 91.67%, 77.78%, 81.82%, 100.00%, 87.50%, 100.00%, 69.23%, and the specificity were 100.00%, 94.12, 87.50%, 89.47%, 97.06%, 96.97%, 94.29%, 89.29% in sputum samples, while in strain samples, the sensitivity were 92.86%, 100.00%, 81.82%, 86.96%, 88.89%, 80.00%, 100.00%, 85.71%. The specificity were 100.00%, 92.86%, 87.10%, 94.74%, 100.00%, 100.00%, 97.14%, 92.86%. Compared with the phenotypic drug susceptibility results, the NGS method has better detection performance for isoniazid, rifampicin, capreomycin, kanamycin, and amikacin in sputum specimens (Kappa≥0.75); while among the strains, the NGS method had a good detection performance for isoniazid, rifampicin, streptomycin, capreomycin, kanamycin, amikacin and levofloxacin (Kappa≥0.75). With the accuracy of the NGS method for detecting strains as a reference, there was no statistically significant difference in the accuracy of all drug resistance detected between strains and sputum specimens. Conclusions: This study showed that the NGS technology was effective in predicting the resistance of isoniazid, rifampicin, and second-line injectable drugs (capreomycin, kanamycin and amikacin) by detecting sputum samples and strain genotypes, suggesting the feasibility and potential of direct detection of sputum samples by the NGS method as an early detection method for drug resistance.
Assuntos
Mycobacterium tuberculosis , Tuberculose dos Linfonodos , Tuberculose Resistente a Múltiplos Medicamentos , Amicacina/farmacologia , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Capreomicina/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Isoniazida/farmacologia , Canamicina/farmacologia , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Rifampina/farmacologia , Escarro/microbiologia , Estreptomicina/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnósticoRESUMO
Objective: We evaluated the safety and efficacy of lipoprotein apheresis (LA) in patients with familial hypercholesterolemia (FH) who can't reach low-density lipoprotein cholesterol(LDL-C) target goals with the maximal tolerated dose of lipid-lowering agents. Methods: This was a retrospective cross-sectional study. Between February 2015 and November 2019, patients with FH who were admitted in Fuwai hospital and treated with LA were consecutively enrolled. Based on intensive lipid-lowering agents, these patients received LA by double filtration plasma pheresis (DFPP) method. The changes of lipid levels such as LDL-C and lipoprotein(a)[Lp(a)] were compared before and after LA treatment, and the changes of immunoglobulin (Ig) concentration and LA-related adverse effects were also discussed. Results: A total of 115 patients with FH were enrolled in this study, of which 8 cases were homozygous FH and 107 cases were heterozygous FH. The age was (43.9±12.2) years and there were 75 (65.2%) males, and 108 (93.8%) with coronary artery disease. For pre-and immediately after LA treatment, the LDL-C was (5.20±2.94) mmol/L vs. (1.83±1.08) mmol/L, Lp(a) concentration was 428.70(177.00, 829.50)mg/L vs. 148.90(75.90, 317.00) mg/L (P<0.001), with a decrease of 64.2% and 59.8% respectively. The levels of IgG and IgA measured 1 day after LA treatment were both in the normal range and IgM concentration was below the reference value, the reductions of which were 15.1%, 25.0% and 58.7% respectively (P<0.001). Six patients had mild symptoms of nausea, hypotension dyspnea and palpitation, the symptoms were relieved by symptomatic treatment. Conclusion: For patients with FH who do not achieve LDL-C target goal with the maximal tolerated lipid-lowering agents, especially those with elevated Lp(a) levels, LA, which can significantly further reduce LDL-C and Lp(a) levels, is an effective and safe option.
Assuntos
Remoção de Componentes Sanguíneos , Hiperlipoproteinemia Tipo II , Lipoproteínas , Adulto , Remoção de Componentes Sanguíneos/métodos , LDL-Colesterol , Estudos Transversais , Feminino , Humanos , Hiperlipoproteinemia Tipo II/terapia , Lipoproteína(a)/química , Lipoproteínas/química , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Diabetes is the most important comorbidity of cardiovascular disease, and cardiovascular disease is the main cause of mortality and disability of patients with type 2 diabetes. In order to standardize the diagnosis and treatment of patients with diabetes and cardiovascular disease, the National Health Commission Capacity Building and Continuing Education Center organized the experts from the field of cardiology and endocrinology systematically reviewing the research progresses and expert experiences of relevant disciplines from home and abroad, and formulated this consensus. This consensus covers the diagnosis, drug treatment, and risk factor management for patients with diabetes and cardiovascular disease (including atherosclerotic cardiovascular disease and heart failure) from the perspective of cardiovascular disease and diabetes management aiming to strengthen the comprehensive management of patients and ultimately to improve the prognosis of patients. The management of cardiovascular diseases mainly includes the management of blood pressure, blood lipids, anti-thrombosis, anti-myocardial ischemia, anti-ventricular remodeling and so on. Diabetes management mainly includes lifestyle intervention (including diet, exercise, weight loss, etc.), anti-hyperglycemia therapy (including drugs and insulin), blood glucose monitoring, and hypoglycemic prevention. In addition, specific clinical recommendations are given to patients with special health care needs such as diabetic nephropathy, elderly (>75 years), and cardiovascular critical illness.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Idoso , Glicemia , Automonitorização da Glicemia , Doenças Cardiovasculares/terapia , Consenso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Humanos , HipoglicemiantesRESUMO
Objective: To identify the value of the detection of pepsin and bile acids in saliva for the diagnosis of gastroesophageal reflux disease(GERD). Methods: From January 2018 to June 2019, 104 GERD patients and 43 healthy people in Guangdong Provincial People's Hospital were recruited. The 104 patients of GERD group were divided into four sub-groups, including esophageal symptoms GERD group, extraesophageal symptoms GERD group, anxiety or depression group, non-anxiety and non-depression group. Saliva was collected on waking in morning and 2 h after finishing lunch. The concentration of the total pepsin(TPP) and total bile acids(TBA) from saliva was detected by ELISA method. Receiver operating characteristics analysis was used to identify the sensitivity and specificity of the saliva pepsin and bile acids detection. Results: The concentration of TPP in morning waking samples and postprandial samples in the GERD group was 27.1(9.7,50.3) µg/L and 32.4(14.0,58.7) µg/L, the concentration of TBA in postprandial samples was (18.4±2.3)µmol/L, and these levels were significantly higher than that of the control group [7.0(5.1, 9.1) µg/L, 7.4(5.2, 9.4) µg/L, (12.6±5.0)µmol/L](P<0.01). The concentration of TBA in morning waking samples had no significant difference between these two groups(P>0.05). The concentration of TPP and TBA had no significant difference among the four GERD sub-groups(P>0.05).Pepsin in postprandial saliva samples had moderate diagnostic value for GERD, when the saliva pepsin concentration in postprandial samples was higher than 41.33 µg/L, it had a sensitivity of 82.8% and a specificity of 73.3%. The bile acids in saliva had no significant diagnostic value for GERD. Conclusions: Pepsin detection in saliva has a high level of sensitivity and specificity for diagnosing GERD. However, bile acids in saliva has no significant diagnostic value for GERD.
Assuntos
Refluxo Gastroesofágico , Ácidos e Sais Biliares , Humanos , Pepsina A , Estudos Prospectivos , SalivaRESUMO
PURPOSE: Though type 2 diabetes mellitus (T2DM) is an important and independent risk factor for coronary artery disease (CAD) in the general population, the impact of T2DM on CAD in patients with familial hypercholesterolemia (FH) is less understood. Thus, the current study aimed to examine the features of FH patients with T2DM and explore the effects of T2DM on CAD in FH. METHODS: A total of 289 clinical heterozygous FH (HeFH) patients diagnosed with Dutch Lipid Clinic Criteria were consecutively recruited and divided into a T2DM group (n = 58) and non-T2DM group (n = 231). Clinical characteristics and laboratory findings were compared between the two groups. Target exome sequencing was used for gene mutation analysis. RESULTS: HeFH patients with T2DM had significantly higher levels of triglycerides, body mass index and free fatty acids than did non-T2DM patients; moreover, patients with T2DM more frequently exhibited hypertension. However, the spectrum of FH-causing mutations was not significantly different (p = 0.061). Notably, patients with T2DM had higher prevalence of CAD (p = 0.012) and higher Gensini Score (p = 0.002). The regression analysis confirmed that HbA1c was an independent risk factor for both the presence and severity of CAD [OR 2.321 (1.098-4.904), p = 0.027; OR 1.349 (1.032-1.762), p = 0.028, respectively] in patients with HeFH. CONCLUSIONS: Although there were not many differences in the clinical, lipid and genetic aspects of HeFH patients with and without T2DM, T2DM and HbA1c were associated with worse coronary lesions, suggesting that diabetes and the degree of blood glucose control are also important determinants of cardiovascular disease in these patients.
Assuntos
Biomarcadores/análise , Doença da Artéria Coronariana/etiologia , Diabetes Mellitus Tipo 2/complicações , Hiperlipoproteinemia Tipo II/complicações , Glicemia/análise , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/patologia , Lipídeos/análise , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Triglicerídeos/metabolismoRESUMO
Ureteral injury can be classified as iatrogenic or traumatic, which represents a rare but challenging field of reconstructive urology. Due to their close proximity to vital abdominal and pelvic organs, the ureters are highly susceptible to iatrogenic injury, while ureteral injury caused by external trauma is relatively rare. The signs of ureteric injury are difficult to identify initially and often present after a delay. The treatment of ureteral injury, which is depended on the type, location, and degree of injury, the time of diagnosis and the patient's overall clinical condition, ranges from simple endoscopic management to complex surgical reconstruction. And long defect of the ureter presents much greater challenges to urologists. Ureterotomy under endoscopy using laser or cold-knife is available for the treatment of 2-3 cm benign ureteral injuries or strictures. Pyeloplasty is an effective treatment for ureteropelvic junction obstruction and some improved methods showed the possibility of repairing long-segment (10-15 cm) stenosis. Proximal and mid-ureteral injuries or strictures of 2-3 cm long can often be managed by primary ureteroureterostomy. When not feasible due to ureteral defects of longer segment, mobilization of the kidney should be considered, and transureteroureterostomy is alternative if the proximal ureter is of sufficient length. And autotransplantation or nephrectomy is regarded as the last resorts. Most of the injuries or strictures are observed in the distal ureter, below the pelvic brim, and are usually treated with ureteroneocystostomy. A non-refluxing technique together with a ureteral nipple or submucosal tunnel method, is preferable as it minimizes vesico-ureteral reflux and the risk of infection. In order to cover a longer distance, ureteroneocystostomy in combination with a psoas hitch (covering 6-10 cm of defect) or a Boari flap (covering 12-15 cm) is often adopted. Among various ureteral replacement procedures, only intestinal ureteral substitution, which includes ileal ureter, appendiceal interposition and reconfigured colon substitution, has gained wide acceptance when urothelial tissue is insufficient. Ileal ureter can be used to replace the ureter of >15 cm defect and even to replace the entire unbilateral ureter or bilateral ureter. Laparoscopic and robotic-assisted techniques are increasingly being employed for ureteral reconstruction and adopted with encouraging results.
Assuntos
Procedimentos de Cirurgia Plástica , Ureter , Obstrução Ureteral , Humanos , Retalhos Cirúrgicos , Ureter/cirurgia , Procedimentos Cirúrgicos UrológicosRESUMO
Objective: To investigate the regulation of long-chain non-coding RNA-AC024560.2 transfection on the expression of miR-30a-5p and its effect on proliferation and invasion of prostate cancer cells. Methods: qRT-PCR was used to detect the expression of AC024560.2 in 16 prostate cancer tissues and adjacent normal tissues, prostate cancer cell lines and normal prostate epithelial cells. The cells with the lowest expression amount were transfected, and the prostate cancer cells were divided into control group (transfected with negative control plasmid) and experimental group (transfected with plasmid carrying AC024560.2). Bioinformatics predicted possible target genes for AC024560.2. qRT-PCR was used to detect the expression of AC024560.2 and target genes in the transfected cells. Western blot was used to detect the expression of downstream target proteins. Cell proliferation and invasion were analyzed by MTS assay and Transwell invasion assay. Results: The expression levels of AC024560.2 in prostate cancer tissues and adjacent tissues were 1.95±0.22 and 3.87±0.23, respectively (t=6.09, P<0.01). Compared with normal prostate epithelial cells, the expression of AC024560.2 in prostate cancer cell lines was significantly decreased (P<0.05), and the most significant decrease was observed in C4-2B cell lines (P<0.01). Bioinformatics predictions showed that AC024560.2 bond to miR-30a-5p, and miR-30a-5p bond to SIRT1 mRNA. The expression of AC024560.2 in the experimental group increased significantly (P<0.01), the expression of miR-30a-5p decreased significantly (P<0.01), and the expression of SIRT1 mRNA and protein increased significantly (P<0.01). After transfection with AC024560.2, the cell proliferation ability of the experimental group was significantly decreased from day 2 (P<0.05). The invasive numbers of C4-2B cells in the control group and the experimental group were 130.90±14.54 and 43.77±10.01, respectively (t=4.94, P<0.01). Conclusions: AC024560.2 is lowly expressed in human prostate cancer, and may inhibit the proliferation and invasion of prostate cancer cells by regulating the expression of miR-30a-5p and SIRT1 genes. AC024560.2 may be a potential target for the treatment of prostate cancer.
Assuntos
Neoplasias da Próstata , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs , Neoplasias da Próstata/genética , RNA Longo não CodificanteRESUMO
BACKGROUND AND AIMS: The role of lipoprotein (a) [Lp(a)] in coronary artery diseases (CAD) with special clinical background such as type 2 diabetes mellitus (T2DM) has not been fully determined. The aim of the present study was to investigate the relation of Lp(a) to type 2 diabetic patients with or without CAD. METHODS AND RESULTS: A total of 2040 consecutive patients with T2DM who received selective coronary angiography (CAG) due to angina-like chest pain were enrolled. The patients were subsequently divided into CAD and non-CAD groups according to the results of CAG. The severity of CAD was evaluated by the Gensini Score (GS), number of stenotic vessels, and history of myocardial infarction (MI). Data showed that Lp(a) levels were higher in the CAD group than in the non-CAD group (median: 15.00 mg/dL vs. 11.88 mg/dL, P = 0.025). The results from CAD subgroup analysis indicated that the patients with MI, multiple-vessel disease and high GS had higher Lp(a) levels compared with those in their matched subgroups (P < 0.05, respectively). After adjustment for confounders, Lp(a) levels were independently related to the presence and severity of CAD (CAD:OR = 1.564; MI:OR = 1.523; high GS:OR = 1.388; multiple-vessel disease:OR = 1.455; P < 0.05, respectively). CONCLUSION: Elevated Lp(a) levels were independently associated with the presence and severity of CAD in patients with T2DM. More studies are necessary to confirm our findings.
Assuntos
Doença da Artéria Coronariana/sangue , Estenose Coronária/sangue , Diabetes Mellitus Tipo 2/sangue , Lipoproteína(a)/sangue , Idoso , Biomarcadores/sangue , China/epidemiologia , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Regulação para CimaRESUMO
Raf kinase inhibitory protein (RKIP) is a well-established metastasis suppressor that is frequently down-regulated in aggressive cancers. However, the impact of RKIP on cancer cell invasion and metastasis in prostate cancer is still elusive. To this end, we overexpressed RKIP in two prostate cancer cell lines. We found that overexpression of RKIP inhibited prostate cancer cells proliferation, migration and invasion. Mechanistically, we found that RKIP overexpression led to down-regula- tion of the NF-kB signaling pathway and inhibition of the epithelial-to-mesenchymal transition, which is important step for cancer metastasis. In addition, overexpression of RKIP can promote drug effects of docetaxel on prostate cancer cell lines. In conclusion, overexpression of RKIP significantly inhibits prostate cancer cell migration and metastasis, and overexpression of RKIP could aid prostate cancer treatment and therapy.
Assuntos
Docetaxel/farmacologia , Metástase Neoplásica , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Neoplasias da Próstata/patologia , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Humanos , Masculino , Proteína de Ligação a Fosfatidiletanolamina/genética , Neoplasias da Próstata/tratamento farmacológico , Transdução de SinaisRESUMO
BACKGROUND: The safety and efficacy of sublingual immunotherapy (SLIT) have been confirmed by many studies. However, in China, the research on efficacy and safety in young and older children with allergic rhinitis (AR) is still rare. OBJECTIVE: The aim of this retrospective study is to evaluate the efficacy and safety of SLIT with Dermatophagoides farinae drops in pre-school and school-age children with AR. METHODS: A total of 282 subjects aged 2-13 years with AR received a two-year course of sublingual immunotherapy along with pharmacotherapy. According to the age, patients were defined as the pre-school group (2-6 years old, n=116) and school-age group (7-13 years old, n=166). Total nasal rhinitis symptom scores (TNSS), visual analogue score (VAS) and total medication scores (TMS) were evaluated at four time points: baseline, after SLIT for half a year, one year and two years. The adverse events (AEs) were evaluated at each visit. RESULTS: After two-year SLIT, the four rhinitis symptom scores, TNSS, VAS and TMS scores were significantly lower than baseline (all P<0.05). The comparison of efficacy between one and two-year duration showed no significant difference in global clinical outcomes (all P>0.05). In addition, there were no significant differences between the pre-school and school-age group in TNSS (all P>0.05), VAS (all P>0.05) and TMS scores (P>0.05) after SLIT for half a year, one year and two years. No severe systemic AEs were reported. CONCLUSION: SLIT with D. farinae drops is clinically effective and safe in pre-school and school-age patients with house dust mites (HDMs)-induced AR.
Assuntos
Antígenos de Dermatophagoides/uso terapêutico , Rinite Alérgica/terapia , Imunoterapia Sublingual/métodos , Adolescente , Animais , Antígenos de Dermatophagoides/imunologia , Criança , Pré-Escolar , China , Dermatophagoides farinae/imunologia , Feminino , Seguimentos , Humanos , Masculino , População , Estudos Retrospectivos , Rinite Alérgica/imunologiaAssuntos
Aterosclerose , Doenças Cardiovasculares , Humanos , Colesterol , Fatores de Risco , TriglicerídeosRESUMO
OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-organ involvement and several typical autoantibodies. Mesenchymal stem cells (MSC) are multipotent stem cells with low immunogenicity that can differentiate into various kinds of cells, such as bone, cartilage, fat and skin tissue. MSC have immunomodulatory and reparative properties through interactions with immune cells. MSC have been used in the treatment of refractory SLE and lupus nephritis patients for more than ten years. Most clinical studies were self-controlled studies and only a few were randomized controlled trials. The objective of this study was to use meta-analysis method to evaluate the efficacy and safety of MSC treatment in SLE patients. METHODS: The PubMed, Cochrane Library, Wanfang and VIP databases were searched for published randomized controlled trials and self-controlled studies before June 1, 2018. The search terms included the Chinese and English versions of mesenchymal stem cells, Mesenchymal Stromal Cells [Mesh], systemic lupus erythematosus, lupus, Lupus Erythematosus, Systemic [Mesh]. Two authors independently screened the literatures, assessed the quality of the studies and collected data according to the inclusion and exclusion criteria. The endpoints were the SLE disease activity index, 24 h urine protein and complement C3. Meta-analysis was performed with the Revman 5.3 software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. RESULTS: Eight studies involving 213 patients were included and three of the studies were randomized controlled trials with 66 patients involved. The MSC group showed that the SLE disease activity index decreased significantly [standard mean difference (SMD)=-1.76, 95% confidence interval (CI): -2.00 to -1.51, P<0.001), the 24 h urine protein decreased significantly (SMD=-1.74, 95%CI: -2.46 to -1.03, P<0.001), as well as the complement C3 increased significantly (SMD=1.28, 95%CI: 0.93 to 1.62, P<0.001). Four studies reported adverse events including fever, diarrhea and headache during the infusion. CONCLUSION: Current evidences showed that MSC could improve the disease activity, proteinuria and hypocomplementemia in SLE patients. Large scale and high-quality randomized controlled trials are required to validate the efficacy and safety of MSC treatment in SLE patients.
Assuntos
Lúpus Eritematoso Sistêmico , Transplante de Células-Tronco Mesenquimais , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/terapia , Nefrite Lúpica , Células-Tronco Mesenquimais , Células-Tronco Multipotentes , Proteinúria/etiologia , Proteinúria/terapia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Objective: To investigate the effect and mechanisms of picroside â ¡ on the brain tissue after cerebral ischemia reperfusion(I/R) in rats. Methods: The middle cerebral artery occlusion(MCAO) rat model was established by inserting a monofilament into middle cerebral artery. The experimental rats were treated by injecting picroside â ¡ intraperitoneally. The modified neurological severity score (mNSS) and body weight were determined before modeling and after reperfusion of 22 h. The cerebral infarct volume was measured by TTC staining and the cerebral water content was measured in rats. At the same time, ROS content and NADPH oxidase activity were detected. The structure of neurons was observed by electron microscope and the mRNA and protein levels of Rac-1 and Nox2 were detected by RT-PCR and Western blotting. Results: After modeling, the mNSS score was significantly increased (12.6±1.3 vs 0, P<0.001), while the body weight was lost (13.3%±2.5% vs 4.9%±0.8%, P<0.01). The cerebral infarct volume increased obviously (33.5%±3.4% vs 0, P<0.001), brain water content increased significantly (81.5%±0.9% vs 77.7%±0.9%, P<0.05) and the structure of neuron was damaged obviously. The protein and mRNA levels of Rac-1 and Nox2 were significantly increased (P<0.05). After treatment with picroside â ¡, mNSS score decreased significantly (7.9±0.8 vs 12.6±1.3, P<0.05) and the body weight increased obviously (9.3%±1.1% vs 13.3%±2.5%, P<0.05). The infarct volume of brain was significantly reduced (18.2%±1.9% vs 33.5%±3.4%, P<0.05), brain water content decreased obviously (79.1%±0.7% vs 81.5±0.9%, P<0.05), the morphological structures of neurons was restored, and the expressions of Rac-1 and Nox2 were significantly decreased (P<0.05). Conclusion: It is suggested that picroside â ¡ could exert antioxidation to protect the brain tissue through inhibiting the expression of Rac-1 and Nox2.
Assuntos
Apoptose , Isquemia Encefálica , Animais , Encéfalo , Cinamatos , Glucosídeos Iridoides , Fármacos Neuroprotetores , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Traumatismo por ReperfusãoRESUMO
Objective: To explore the effect of picroside â ¡ on the expression of mitochondrial voltage-dependent anion channel 1 (VDAC1) in rats after cerebral ischemiareperfusion. Methods: A total of 70 Wistar rats models with middle cerebral artery occlusionreperfusion (MCAO/R) were randomly divided into the sham group, model group, picroside (Picr) group, ruthenium red (RuR) group, RuR+ Picr group, Spermine (Sper) group, Sper+ Picr group (n=10 per group). Modified neurological severity scale (mNSS) was used to evaluated the neurobehavioral function, the expression of reactive oxygen species (ROS) in brain tissues were measured by enzyme-linked immunosorbent assay (ELISA), the morphology of brain tissues was observed by hematoxylin-eosin (HE) staining, the apoptotic cells were counted by terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL), and the expressions of VDAC1 and endonuclease G (EndoG) were determined by immunohistochemical assay and Western blot. Results: Compared with the shame group, the mNSS scores (9.6±1.9), the expression of ROS[(47.6±2.7)U/ml], the apoptosis of neuron(23.8±2.8), and the expressions of VDAC1(0.94±0.06) and EndoG in cytoplasm (0.76±0.06) and nuclei(0.75±0.06)were enhanced in the model group (all P<0.05). The Picr group had obviously decreased mNSS scores (5.7±0.9), ROS expression[(35.6±2.2)U/ml], number of apoptotic cells (14.5±2.1), VDAC1 (0.63±0.06) and EndoG in cytoplasm (0.34±0.05) and nuclei (0.31±0.06)expressions compared to the model group (P<0.05). Conclusion: Picroside â ¡ could attenuate cerebral I/R injury by down-regulating the expression of VDAC1 and inhibiting the EndoG release from mitochondria into cytoplasm.
Assuntos
Isquemia Encefálica , Animais , Apoptose , Cinamatos , Glucosídeos Iridoides , Fármacos Neuroprotetores , Ratos , Ratos Wistar , Traumatismo por ReperfusãoRESUMO
Objective: To investigate the value of single nucleotide polymorphism array (SNP-array) for fetuses with abnormal ultrasound findings. Method: A total of 904 fetuses with abnormal ultrasound findings were enrolled in this study from May 2015 to November 2017, and 434 (48.0%) cases received conventional karyotyping analysis at the same time. According to different abnormal ultrasound category, 904 cases were divided into 5 groups: 280 cases (31.0%) in single system structural anomalies, 31 cases (3.4%) in multiple system structural anomalies, 331 cases (36.6%) in single ultrasound soft marker abnormalities without structural anomalies, 107 cases (11.8%) in multiple soft marker abnormalities and 155 cases (17.2%) in structural abnormalities combined with soft markers abnormalities. Abnormal detection rates by SNP-array among 5 groups of abnormal ultrasound category were calculated. Result: (1) Total SNP-array results: 171 (19.0%) cases out of 904 cases analyzed by SNP-array, presented chromosomal abnormalities. Pathogenic copy number variants were detected in 27 cases (3.0%) and variants of unknown significance were detected in 81 cases (7.8%) . In addition, 7 cases (26.0%) were found with new mutation by parental validation. (2) SNP-array of 5 groups: among the 5 groups of abnormal ultrasound category, chromosomal abnormalities were identified by SNP-array in 19.3% (54/280) with single system structural abnormalities, 25.8% (8/31) with multiple system structural abnormalities, 13.9% (46/331) with single nonstructural anomalies, 19.6% (21/107) with multiple nonstructural anomalies and 27.1% (42/155) with structural abnormalities combined with nonstructural anomalies. The differences were significant (P=0.010) . No chromosome abnormalities was identified in single soft marker abnormalities, such as choroid plexus cysts, echogenic foci in the heart, single umbilical artery and pyelectasis. (3) Chromosomal abnormalities: the abnormal detection rate of aneuploidy chromosomal abnormalities by SNP-array increased with the maternal age, decreased with the gestational weeks (all P<0.05) . However, the pathogenic copy number variants and variants of unknown significance rates did not change with maternal age and gestational weeks (all P>0.05) . (4) SNP-array and karyotyping: 434 cases were analyzed by conventional karyotyping and SNP-array respectively, 10.3% (43/419) of which presented chromosomal abnormalities by conventional karyotyping and 18.7% (81/434) of which presented chromosomal abnormalities by SNP-array. Conclusions: SNP-array could be a useful genetic analysis method in prenatal diagnosis for fetuses with abnormal ultrasound findings. For different abnormal ultrasound category, SNP-array has different detection rate. Compared with conventional karyotyping analysis, SNP-array can improve the detection rates for chromosomal abnormalities and find the chromosome abnormalities which can't be detected by conventional karyotyping analysis. In clinical prenatal genetic counseling, SNP-array should be selected rationally in combination with the various abnormal ultrasound category.
Assuntos
Anormalidades Múltiplas/genética , Transtornos Cromossômicos/genética , Anormalidades Congênitas/genética , Variações do Número de Cópias de DNA , Cariotipagem/métodos , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Nucleotídeo Único , Diagnóstico Pré-Natal/métodos , Ultrassonografia Pré-Natal/métodos , Anormalidades Múltiplas/diagnóstico por imagem , Aneuploidia , Aberrações Cromossômicas , Anormalidades Congênitas/diagnóstico por imagem , Feminino , Feto , Aconselhamento Genético , Testes Genéticos , Humanos , Idade Materna , GravidezRESUMO
Objective: To observe the clinical efficacy of Ningmitai capsules, a traditional Chinese medicine using for clearing heat and dampness, in the treatment of residual fragments and postoperative complications following lithotripsy for upper urinary stones. Methods: During October 2016 and March 2018, patients from Wuhan 1st Hospital, Wuhan 2nd Hospital, Wuhan 3rd Hospital, and Wuhan Puai Hospital having upper urinary residual fragments following minimally-invasive stone treatment were randomly assigned to control group and Ningmitai group with a proportion of 1â¶3. The patients in control group were treated with antibiotics or sodium diclofenac suppository on demand, while patients in Ningmitai group took additional Ningmitai capsule orally (4 capsules per time, 3 times per day). The observation was started when a patient was enrolled in this study and continued for a maximum of 12 weeks or until stone-free status. During the observation, the stone expulsion time, stone-free time, stone-free rate were observed, and the difference in curative effect between the two groups on postoperative complications such as pain and infection were compared. Statistical analysis was done using t-test or χ2 test by GraphPad Prism 5 software. Results: Totally 269 cases enrolled in this study. Eighty-six patients were from Wuhan 1st Hospital, 69 patients from Wuhan 2nd Hospital, 58 patients from Wuhan 3rd Hospital, 56 patients from Wuhan Puai Hospital, respectively. There were 66 cases in control group and 203 cases in Ningmitai group. The residual fragments expulsion time in Ningmitai group was significantly earlier than that in control group ((4.5±0.4) days vs. (7.5±1.3) days, t=2.877, P=0.004), the residual fragments clearance time in Ningmitai group was significantly shorter than that in control group ((13.6±1.0) days vs.(25.6±3.8) days, t=4.252, P=0.000), and the stone-free rate within 4 weeks post operation in Ningmitai group was significantly higher than control group (91.6% vs. 68.2%, χ2=22.57, P=0.000). After 12 weeks of treatment, the total effective rate of control group was 89.4%, and the total effective rate of Ningmitai group was 99.5%, with statistically significant difference (χ2=17.65, P=0.000). The proportion of caregivers that offered analgesia in Ningmitai group was significantly lower than that in control group (16.3% vs. 30.3%, χ2=6.212, P=0.013), the recovery rate of routine urinalysis following 4 weeks' treatment was significantly higher in Ningmitai group than that in control group (88.2% vs.71.2%, χ2=10.67, P=0.001). No obvious adverse effects were observed in both groups. Conclusions: Ningmitai capsule can facilitate the stone passage and increase the stone-free rate in the treatment of residual fragments and postoperative complications of upper urinary stones. It is also helpful for the prevention and treatment of postoperative pain, infection and other complications.
Assuntos
Litotripsia , Medicina Tradicional Chinesa , Cálculos Urinários , Cápsulas , Humanos , Complicações Pós-Operatórias , Resultado do Tratamento , Cálculos Urinários/terapiaRESUMO
Objectives: To investigate the prevalence rate and clinical characteristics of familial hypercholesterolemia (FH) in Chinese patients undergoing coronary angiography due to angina-like chest pain. Methods: From March 2011 to December 2016, a total of 9 908 consecutive patients undergoing coronary angiography in Fuwai Hospital due to angina-like chest pain were enrolled. The age of enrolled patients was (56.6±11.1) years old, and 6 782 cases (68.4%) were male. The patients were divided into two groups: FH group (n=271) and non-FH group (n=9 637) according to the Dutch Lipid Clinic Network diagnostic criteria. A retrospective analyze was performed on the baseline features between the two groups including lipids levels, coronary artery disease (CAD) characteristics, and lipids-lowering treatments. Results: In the total cohort, the prevalence of definite/probable FH was 2.7% (271/9 908). The incidence of premature coronary artery disease (PCAD) (women < 60 years old, or men < 55 years old) was higher in patients with FH than that in patients without FH (70.2%(201/271) vs. 44.5% (4 287/9 637); χ(2)=93.738, P<0.001). Patients with FH had higher level of TC and LDL-C when compared with patients without FH ((6.74±2.48) mmol/L vs. (4.15±1.10) mmol/L; (4.53±2.39) mmol/L vs. (2.52±0.97) mmol/L; t=19.403, 22.233, P<0.001, respectively). Additionally, 84.9% (230/271) of FH patients were treated with statin at different intensities, but none of them achieved the LDL-C<2.6 mmol/L. Conclusions: Chinese patients with familial hypercholesterolemia not only showed a high presence of PCAD and higher lipids levels, but also exhibited a low rate of achievement of low-density lipoprotein cholesterol targets despite statin therapy. Our results thus highlight the importance of early diagnosis and intensive treatment of FH patients.
Assuntos
Doença da Artéria Coronariana/patologia , Hiperlipoproteinemia Tipo II/patologia , Idoso , Dor no Peito , China/epidemiologia , LDL-Colesterol , Angiografia Coronária , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos RetrospectivosRESUMO
Objective: To analyze the prevalence and clinical features of familial hypercholesterolemia (FH) in Chinese patients with myocardial infarction (MI). Method: This retrospective study recruited a total of 2 119 consecutive patients (age (56.7±10.9) years old) undergoing coronary angiography with first MI from April 2011 to December 2016. Patients were divided into 2 groups: premature MI (male<55 years old, female<60 years old) and non-premature MI. The diagnosis of FH was established according to Dutch Lipid Clinic Network (DLCN) diagnostic criteria and referred as definite/probable FH in our study. The prevalence and clinical features of FH, including lipid level, MI characteristics and stain therapy, were explored. Multivariable logistic regression analysis was used to assess the predictive value of FH for the presence of premature MI. Results: The prevalence of definite/probable FH was 3.68% (78/2 119) in MI patients and 7.28% (68/934) in premature MI patients. Onset of MI occurred 10 years earlier in patients with definite/probable FH than those without FH ((47.9±9.4) years vs. (58.8±10.7) years, P<0.01). Additionally, we found that the risk of premature MI was significantly and independently increased in definite/probable FH patients (OR=5.32, 95%CI 2.77-10.22, P<0.01). None of FH patients reached the target of LDL-C<1.8 mmol/L under statin therapy. Conclusions: The prevalence of FH in Chinese patients with MI is not rare. Clinically, FH is linked with the early onset of MI.
Assuntos
Hiperlipoproteinemia Tipo II/patologia , Infarto do Miocárdio/complicações , Adulto , Povo Asiático , China/epidemiologia , LDL-Colesterol , Angiografia Coronária , Feminino , Humanos , Hiperlipoproteinemia Tipo II/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/patologia , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To investigate the mechanisms of nuclear export signal of androgen receptor (NESAR) in the regulation of androgen receptor (AR) protein expression and stability in prostate cancer. METHODS: The green fluorescent protein fusion protein expression vectors pEGFP-AR(1-918aa), pEGFP-NESAR (743-817aa), pEGFP-NAR (1-665aa) and pEGFP-NAR-NESAR, and lysine mutants of NESAR pEGFP-NESAR K776R, pEGFP-NESAR K807R and pEGFP-NESAR K776R/K807R, were transiently transfected into prostate cancer cell line PC3. Fluorescence microscopy, Western blot and immunoprecipitation were used to detect NESAR regulation of androgen receptor stability. RESULTS: Under the fluorescence microscope, NESAR-containing fusion proteins were cytoplasmic localization, and their fluorescence intensities were much weaker than those without NESAR. The expression levels of NESAR-containing fusion proteins were significantly lower than those without NESAR. The half-lives of GFP-NESAR and GFP-NAR-NESAR were less than 6 h, while the expression of GFP and GFP-NAR was relatively stable and the half-life was more than 24 h in the presence of cycloheximide. The expression levels of GFP-NESAR were significantly increased by proteasome inhibitor MG132 treatment in a dose-dependent manner; in contrast, MG132 did not show any significant effect on the protein levels of GFP. When new protein synthesis was blocked, MG132 could also prevent the degradation of GFP-NESAR in the transfected cells in the presence of cycloheximide, while it had no significant effect on GFP protein stability in the parallel experiment. GFP immunoprecipitation showed that the ubiquitination level of GFP-NESAR fusion protein was significantly higher than that of the GFP control. The mutations of lysine sites K776 and K807 in NESAR significantly reduced the level of ubiquitination, and showed increased protein stability, indicating that they were the key amino acid residues of NESAR ubiquitination. CONCLUSION: NESAR was unstable and decreased the stability of its fusion proteins. NESAR was the target of polyubiquitination and mediated the degradation of its fusion proteins through the ubiquitin-proteasome pathway in prostate cancer cells. Our research provides a new way to regulate the level and/or activity of AR proteins, thus helping us understand the molecular mechanisms of AR degradation and strict control of AR in the progression to castration-resistance.