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1.
Cancer Radiother ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32044160

RESUMO

PURPOSE: The role of prophylactic cranial irradiation (PCI) in treatment of extensive-stage small-cell lung cancer (SCLC) is controversial. The aim of this study was to systematically evaluate the efficacy and safety of using PCI in the treatment of extensive-stage SCLC. In the present study, we examined whether PCI was essential for the optimal treatment of extensive-disease small-cell lung cancer. MATERIAL AND METHODS: We searched the PubMed, Embase, Medline, and China National Knowledge Infrastructure databases to identify articles that assessed the efficacy of PCI in treating extensive-stage small-cell lung cancer patients. RESULTS: We identified 8 studies that involved a total of 982 patients who received PCI (PCI group) and a total of 4509 patients who did not receive PCI (control group). The results showed that PCI significantly improved the 1-year overall survival rate (HR=1.50; 95% CI: 1.23-1.82; I2=67%; P<0.0001) and reduced the incidence of brain metastasis (HR=0.46; 95% CI: 0.37-0.58; I2=6%; P<0.00001). CONCLUSION: PCI improves the 1-year overall survival rate and reduces the risk of brain metastasis in patients with extensive-stage SCLC.

2.
Lupus ; : 961203320905668, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054395

RESUMO

OBJECTIVE: This study aimed to identify the clinical characteristics and prognostic factors of systemic lupus erythematosus with transverse myelitis (SLE-TM) in a relatively large patient series. METHODS: This retrospective study considered 45 SLE-TM individuals treated as inpatients and outpatients at Peking Union Medical College Hospital between 1993 and 2018. SLE-TM patients were compared with 180 controls, and SLE-TM patients with neuromyelitis optica spectrum disorder (NMOSD) were compared to those without NMOSD. RESULTS: Compared to controls, the SLE-TM group frequently had a fever and had a significantly higher positive rate of anticardiolipin and lupus anticoagulant. Among the 45 patients, 22 met the NMOSD criteria. Compared to non-NMOSD patients, NMOSD patients had a lower incidence of rash (p = 0.023), serositis (p = 0.042) and renal disorder (p = 0.073); a lower prevalence of decreased complement (p = 0.083); and lower rates of positive anti-dsDNA (p = 0.074) and anti-Sm (p = 0.042). Among 22 SLE-TM patients with NMOSD, 18 underwent aquaporin 4 antibody testing, with 11 showing positive results. Out of the 45 patients, 39 were given methylprednisolone pulse treatment. After treatment, 32 patients had lower-limb muscle strength recovery (recovered group), whereas 13 had no change and persistent severe neurological deficits (non-recovered group). Compared to the recovered group, the non-recovered group were younger (p = 0.002), had a higher likelihood of having a fever (p = 0.020), initial severe myelitis (p < 0.001), long spinal segment involvement (p = 0.017) and higher C-reactive protein levels (p = 0.020). Methylprednisolone pulse given within two weeks of onset was more frequent in the recovered group than in the non-recovered group (p = 0.082). CONCLUSIONS: Disease characteristics differed between SLE-TM patients with and without NMOSD. SLE and NMOSD tended to be co-morbidities. Initial severe neurological impairment, extensive spinal cord lesions, hyper-inflammation and delayed steroid impulse treatment could be predictors of poor outcome for SLE-TM.

3.
Artigo em Chinês | MEDLINE | ID: mdl-32062887

RESUMO

Objective: To investigate the antagonistic effect of diallyl sulfide (DAS) against peripheral nerve injury induced by n-hexane in rats. Methods: A total of 68 adult male Wistar rats were selected, among which 50 were randomly selected and divided into blank control group, DAS control group (100 mg/kg·bw) , n-hexane model group, low-dose DAS intervention group (50 mg/kg·bw) , and high-dose DAS intervention group (100 mg/kg·bw) . A rat model of peripheral nerve injury was established by n-hexane exposure, and the rats were treated with DAS at different doses. The changes in pyrrole adducts and behavior were observed, a metabolic analysis was performed for serum pyrrole adducts, and the intervention effect was evaluated. The remaining 18 rats were randomly assigned to the n-hexane model group, the low-dose DAS intervention group, and the high-dose DAS intervention group, with 6 rats in each group, as satellite groups used for the toxicokinetic analysis of serum pyrrole adducts. Results: Compared with the blank control group, the n-hexane model group and low-and high-dose DAS intervention groups had a significant reduction in body weight since week 2 (P<0.01) . Compared with the n-hexane model group at the end of the experiment at week 7, the high-dose DAS intervention group had a significantly higher body weight (P<0.05) , while there was no significant difference in body weight between the n-hexane model group and the low-dose DAS intervention group (P>0.05) . The n-hexane model group developed gait abnormality at week 2 of poisoning, while the low-and high-dose DAS intervention groups developed gait abnormality at weeks 3 and 5 of poisoning, respectively. At the end of the experiment, the n-hexane model group and the low-and high-dose DAS intervention groups had a significantly higher gait score than the blank control group (P<0.01) . At the end of the experiment, the n-hexane model group and the low-dose DAS intervention group had significantly shorter latency in rotarod test than the blank control group (P<0.01) , while there was no significant difference in latency between the DAS control group and the high-dose DAS intervention group (P>0.05) . Compared with the n-hexane model group, the low-and high-dose DAS intervention groups had a significant increase in latency in rotarod test (P<0.01) . Compared with blank control group, the n-hexane model group and the low-dose DAS intervention group had a significant increase in mean nerve conduction velocity (P<0.01) , while there was no significant difference between the blank control group and the DAS control group or high-dose DAS intervention group (P>0.05) , and compared with the n-hexane model group, the low-and high-dose DAS intervention groups had a significant increase in nerve conduction velocity (P<0.01) . Compared with the blank control group at the end of the experiment at week 7, the n-hexane model group and the low-and high-dose DAS intervention groups had significant increases in the concentration of pyrrole adducts in serum, urine, and hair (P<0.01) , while there was no significant difference between the blank control group and the DAS control group (P>0.05) , and the high-dose DAS intervention group had a significantly lower concentration of pyrrole adducts in serum, urine, and hair than the low-dose DAS intervention group (P<0.05) . Serum pyrrole adducts reached the peak level at 9-12 hours and then started to decrease. Compared with the n-hexane model group, the high-and low-dose DAS intervention groups had a significantly shorter half-life period of serum pyrrole adducts (P<0.01) . Compared with the n-hexane model group, the high-and low-dose DAS intervention groups had a significant reduction in the area under the curve of serum pyrrole adducts (P<0.05) . Conclusion: DAS can antagonize peripheral nerve injury induced by n-hexane.

4.
Poult Sci ; 99(2): 1124-1134, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32036964

RESUMO

Curcumin has antioxidant functions, regulates the intestinal microbial composition, and alleviates mycotoxin toxicity. The present study aimed to explore whether curcumin could alleviate ochratoxin A (OTA)-induced liver injury via the intestinal microbiota. A total of 720 mixed-sex 1-day-old White Pekin ducklings were randomly assigned into 4 groups: CON (control group, without OTA), OTA (fed a diet with 2 mg/kg OTA), CUR (ducks fed a diet with 400 mg/kg curcumin), and OTA + CUR (2 mg/kg OTA plus 400 mg/kg curcumin). Each treatment consisted of 6 replicates and 30 ducklings per replicate. Treatment lasted for 21 D. Results were analyzed by a two-tailed Student t test between 2 groups. Our results demonstrated that OTA treatment had the highest serum low-density lipoprotein (LDL) level among 4 groups. Compared with OTA group, OTA + CUR decreased serum LDL level (P < 0.05). OTA decreased liver catalase (CAT) activity in ducks (P < 0.05), while addition of curcumin in OTA group increased liver CAT activity (P < 0.05). 16S ribosomal RNA sequencing suggested that curcumin increased the richness indices (ACE index) and diversity indices (Simpson index) compared with OTA group (P < 0.05) and recovered the OTA-induced alterations in composition of the intestinal microbiota. Curcumin supplementation relieved the decreased abundance of butyric acid producing bacteria, including blautia, butyricicoccus, and butyricimonas, induced by OTA (P < 0.05). OTA also significantly influenced the metabolism of the intestinal microbiota, such as tryptophan metabolism and glyceropholipid metabolism. Curcumin could alleviate the upregulation of oxidative stress pathways induced by OTA. OTA treatment also increased SREBP-1c expression (P < 0.05). The curcumin group had the lowest expression of FAS and PPARG mRNA (P < 0.05) and the highest expression of NRF2 and HMOX1 mRNA. These results indicated that curcumin could alleviate OTA-induced oxidative injury and lipid metabolism disruption by modulating the cecum microbiota.

5.
Neoplasma ; 2020 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-32039631

RESUMO

This study aimed to create prognostic signatures to predict AML patients' survival using alternative splicing (AS) events. The AS data, RNA sequencing data, and the survival statistics of 136 AML patients were obtained from The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases. Total 34,984 AS events generated from 8,656 genes, 2,583 of which were survival-associated AS events, were identified using univariate Cox regression. The prognostic models constructed using independent survival-associated AS events revealed that low-risk splicing better predicted patients' survival. ROC analysis indicated that the predictive efficacy of the alternate terminator model was best in the area under the curve at 0.781. Enrichment analysis revealed several important genes (TP53, BCL2, AURKB, PPP2R1B, FOS, and BIRC5) and pathways, such as the protein processing pathway in the endoplasmic reticulum, RNA transport pathway, and HTLV-I infection pathway. The splicing network of splicing events and factors revealed interesting interactions, such as the positive correlation between HNRNPH3 and CALHM2-13010-AT, which may indicate the potential splicing regulatory mechanism. Taken together, survival-associated splicing events and the prognostic signatures for predicting survival can help provide an overview of splicing in AML patients and facilitate clinical practice. The splicing regulatory network may improve the understanding of spliceosomes in AML.

6.
Anim Genet ; 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31981462

RESUMO

We detected growth-related QTL and associated markers from the backcross population of Exopalaemon carinicauda in the previous study. Based on our previous study, the 47 SNP markers associated with candidate growth trait QTL were selected to analyze the association between these markers and body weight (BW), body length and abdominal segment length traits in four different populations including wild population, a full-sib family, a half-sib family and a backcross population for evaluating their potential application of marker-assisted selection in E. carinicauda. The general linear model (GLM) and mixed linear model were applied and the associations between SNP loci and three growth-related traits verified. The results showed that the Marker79268 and Marker100644 were significantly associated with the BW trait in more than three populations by the GLM method. The Marker100644 was significantly associated with BW in the full-sib family, half-sib family and backcross populations by the GLM and mixed linear model methods. Our findings will provide useful SNP markers to go forward to improve growth performance through more refined marker-assisted selection in E. carinicauda.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31904566

RESUMO

OBJECTIVES: Data from clinical trials of human papillomavirus (HPV) vaccines showed that women naïve (negative for both type-specific antibodies and DNA) to vaccine types would derive benefit from vaccination; therefore, an understanding of the proportion of naïve women in different age groups is important for developing HPV vaccination strategies. METHODS: From November 2012 to April 2013, a total of 7372 healthy women aged 18-45 years were recruited in five provinces in China. Cervical specimens and serum samples were collected for each woman at entry. Cervical specimens were first tested by the HPV DNA enzyme immunoassay method; if positive, the specimens were then tested by reverse hybridization line probe assay and HPV-16 and HPV-18 specific polymerase chain reactions. Neutralizing antibodies against HPV-16 or HPV-18 were tested with a pseudovirion-based neutralization assay. RESULTS: The overall prevalence of high-risk HPV DNA was 14.8% (1088/7367, 95% CI 14.0-15.6), and the seroprevalence of neutralizing antibodies against HPV-16 and HPV-18 was 12.6% (925/7367) and 4.9% (364/7367), respectively. In younger women (18-26 years) and middle-aged women (27-45 years), 83.8% (3116/3719) and 81.4% (2968/3648) were naïve to both HPV-16 and HPV-18 (both neutralizing antibodies and DNA were negative), respectively. In addition, 98.5% (3664/3719) and 98.0% (3575/3648) of the younger or middle-aged women were naïve to at least one HPV type (HPV-16 or HPV-18). DISCUSSION: This study revealed that the majority of Chinese women aged 18-26 years and 27-45 years were naïve to both HPV-16 and HPV-18 and would thus derive full benefit from bivalent HPV vaccination.

8.
Artigo em Chinês | MEDLINE | ID: mdl-31954384

RESUMO

Objective: To analyse the outcomes and the prognostic factors of patients with sinonasal malignancies following endoscopic endonasal approach, and to compare the pre- and post-operative quality of life. Methods: A retrospective single-center review of 79 patients who underwent endoscopic endonasal approach for sinonasal malignancies in Beijing Tongren Hospital from October 2004 to March 2017 was performed, including 51 males and 28 females, with a median age of 48 years. Data of demography, imaging (including nasal CT and MRI before operation), histopathology and treatment strategy were collected. Recurrence and distant metastasis were diagnosed according to endoscopic examination, MRI and general check-up after surgery. Pre- and post-operative quality of life scores were obtained by sinonasal outcome test-22, visual analog scale and anterior skull base surgery questionnaire. SPSS 22 software was used for statistical analysis. Results: The study consisted of 13 pathological types with sinonasal T1-T4 stage tumors, including cervical lymph nodes and/or distant metastasis. All patients underwent endoscopic endonasal approach surgery. After 43 months of median follow-up time, the overall, disease-free, and recurrence-free survival rates at 1, 3, 5 and 10 years was 97.4%, 92.5%, 92.5% and 83.7%; 83.2%, 68.3%, 56.8% and 33.6%; 84.5%, 66.6%, 58.0% and 34.4%, respectively. Postoperative recurrence was an independent risk factor affecting the overall survival rate (HR=8.852, P=0.044), and preoperative recurrence (secondary surgery) was an independent risk factor affecting the disease-free and recurrence-free survival rate (HR value was 2.237 and 2.095 respectively, P value was 0.029 and 0.047 respectively). After surgery, the olfaction and nasal scab got worse, while the nasal obstruction and breathing were improved. Conclusions: Endoscopic endonasal approach for sinonasal malignancies can achieve satisfactory outcomes, and has obvious advantages in improving the quality of life. Postoperative recurrence and preoperative recurrence are the prognostic factors.


Assuntos
Endoscopia/métodos , Neoplasias dos Seios Paranasais/cirurgia , Qualidade de Vida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
9.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(1): 51-55, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-31958931

RESUMO

Objective: To investigate the Clavien-Dindo (CD) classification of complications after complete mesocolic excision (CME) in laparoscopic radical resection of right-sided hemicolon cancer and its influencing factors. Methods: A retrospective case-control study was performed. Inclusion criteria: (1) the adenocarcinoma located at colon from cecum to hepatic flexure; (2) laparoscopic right hemicolectomy with CME was completed. Exclusion criteria: (1) patients had severe organ dysfunction before operation; (2) tumor invaded adjacent organs or developed distant organ metastasis; (3) emergency surgery; (4) failure of laparoscopic surgery, and conversion to laparotomy; (5) without complete clinical data. Finally, clinical data of 141 patients in our hospital form March 2015 to February 2019 were retrospectively analyzed. CD grading standard was used to evaluate postoperative complications. Univariate and multivariate logistic regression analyse were used to analyze the factors that might affect the complications. Survival analysis was conducted by grouping the indicators with statistically significant difference in multivariate analysis. Kaplan-Meier method was used to draw the survival curve and log-rank test was used to analyze the difference. Results: Of the 141 patients, 89 were male and 52 were female with mean age of (61.8±11.0) years. All the operations completed successfully. A total of 37 postoperative complications were developed in 26 (18.4%) patients had postoperative 37 cases of complications, mainly including 7 delayed incision healing, 6 diarrhea, and 5 respiratory dysfunction. According to CD classification standard, grade I, II, and IV a complication rates were 40.5% (15/37), 56.8% (21/37), and 2.7% (1/37) respectively. Univariate analysis showed that age ≥ 65 years (χ(2)=4.338, P=0.037), BMI ≥ 28 kg/m(2) (χ(2)=5.971, P=0.015), and preoperative hemoglobin < 100 g/L (χ(2)=3.985, P=0.046) were risk factors of postoperative complications. Multivariate analysis testified that age ≥ 65 years (OR=7.991, 95%CI: 2.203 to 28.983, P=0.002) and body mass index (BMI) ≥ 28 kg/m(2) (OR=4.231, 95%CI: 1.034 to 17.322, P=0.045) were independent risk factors for complications after laparoscopic CME surgery for right-sided hemicolon cancer. All the patients were followed up for median time of 24 (1-48) months. The log-rank test showed that there were no significant differences in the cumulative survival rate between patients of age < 65 years and age ≥ 65 years (χ(2)=0.986, P=0.321), and between those with BMI < 28 kg/m(2) and BMI ≥ 28 kg/m(2) (χ(2)=0.370, P=0.543). Conclusions: The main complications after CME in laparoscopic radical resection of right hemicolon cancer are CD grade I and II. Elderly and obesity are independent risk factor for postoperative complications. Before the operation, reasonable preventive measures should be taken for the elderly and the obese in order to reduce postoperative complications.


Assuntos
Colectomia/efeitos adversos , Neoplasias do Colo/cirurgia , Mesocolo/cirurgia , Fatores Etários , Idoso , Colectomia/métodos , Neoplasias do Colo/complicações , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Complicações Pós-Operatórias/classificação , Estudos Retrospectivos , Resultado do Tratamento
10.
Lupus ; 29(1): 45-51, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31793380

RESUMO

BACKGROUND: We established a multi-centre online registry for primary Sjögren's syndrome (pSS) in China, and compared Chinese patients with those from other countries. METHODS: Data were from 87 rheumatology centres in 27 provinces. All 2986 patients had pSS according to the 2002 American-European Consensus Group or the 2016 American College of Rheumatology/European League Against Rheumatism. All centres used the same methods. Data on demographics, clinical parameters, laboratory results, disease activity and treatments were examined. RESULTS: The female:male ratio was 22.9:1, and the mean age at onset was 46.31 years. A total of 332 (11.1%) patients had thyroid disease, including hyperthyroidism (1.2%), hypothyroidism (6.0%) and subacute thyroiditis (3.9%). Dry eye had a prevalence of 68.59% in Chinese patients, 93.7-96% in European patients and 97.3% in American patients. Dry mouth had a prevalence of 86.5% in Chinese patients, 93.2-96% in European patients and 97.9% in American patients. Fewer Chinese than European patients had arthritis (6.9% vs. 15-19.3%). ANA positivity was 90.7% in Chinese, 81.3% in European and 77.6% in American patients. Anti-SSA antibody positivity was 84.6% in Chinese, 71% in European and 68.2% in American patients. The most commonly used drugs in Chinese patients were hydroxychloroquine (n = 1818; 67.5%), glucocorticoids (n = 1720; 63.9%) and total glucosides of paeony (n = 1120; 41.7%). CONCLUSIONS: This study provided information on the phenotypes of Chinese patients with pSS, and identified several differences with patients from other geographical regions.

11.
Osteoporos Int ; 31(1): 165-173, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31642976

RESUMO

This study evaluated bone features of PHPT using HR-pQCT. The results showed both cortical and trabecular bones were significantly impaired in PHPT patients. Male and female PHPT patients suffered similar damages in bone. HR-pQCT indices were not observed to differ in MEN1 and sporadic PHPT patients. INTRODUCTION: High-resolution peripheral quantitative CT is a novel imaging technique used to separately assess trabecular and cortical bone status of the radius and tibia in vivo. Using HR-pQCT, we aimed to evaluate bone features of primary hyperparathyroidism patients in a Chinese population and reveal similarities and differences in bone features in multiple endocrine neoplasia type 1-related PHPT and sporadic PHPT patients in the Chinese population. METHODS: A case-control study was designed. In 58 PHPT patients and 58 sex- and age-matched healthy controls, the distal radius and tibia were scanned using HR-pQCT. Areal bone mineral density (aBMD) was also determined in PHPT patients using dual-energy X-ray absorptiometry (DXA). RESULTS: In comparison with controls, PHPT patients were observed to exhibit reduced volumetric BMD at the cortical and trabecular compartments, thinner cortices, and more widely spaced trabeculae. Significant differences were still observed when comparing data of female and male patients with age-matched controls separately. MHPT patients (n = 11) were found to have lower aBMD Z-scores in the lumbar spine, trochanteric region, and total hip compared with sporadic PHPT patients (n = 47), while no differences were observed in HR-pQCT indices between the two groups. In multiple linear regression models, no significant correlations were identified between PTH and HR-pQCT indices. However, height was found to positively correlate with HR-pQCT-derived trabecular indices at both the radius and tibia. CONCLUSIONS: PHPT affects geometry, volumetric density, and microstructure in both the cortical and trabecular bones in both male and female Chinese patients. MHPT patients were observed to have reduced aBMD as determined by DXA in the lumbar spine and hip in comparison with sporadic PHPT patients. However, HR-pQCT indices were not observed to differ.

12.
Osteoporos Int ; 31(1): 153-164, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31646353

RESUMO

This study aimed to investigate the bone impairment in finger joints in PHO patients by HR-pQCT. Results showed distinguished differences in bone architecture and biomechanics parameters at DIPs between PHO patients and healthy controls using HR-pQCT assessment. Besides, serum PGE2, hsCRP and ESR levels were found negatively correlated with total vBMD. INTRODUCTION: This study aimed to investigate the bone impairment in finger joints in primary hypertrophic osteoarthropathy (PHO) patients firstly by high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Fifteen PHO patients and 15 healthy controls were enrolled in this study. Bone erosions in hands at distal interphalangeal joints (DIPs) in both PHO patients and controls were evaluated by X-ray. Bone geometry, vBMD, microstructure parameters, and size of individual bone erosion were also measured at the 3rd DIP by HR-pQCT as well. Blood biochemistry levels between the two groups were also compared. RESULTS: Compared to X-ray, HR-pQCT assessment were more sensitive for detection of bone erosions, with 14 PHO patients by HR-pQCT versus ten PHO patients by X-ray judged at the 3rd DIP. The average depth, width, and volume of erosions size in PHO patients were 1.38 ± 0.80 mm, 0.79 ± 0.27 mm, and 1.71 ± 0.52 mm3, respectively. The bone cross-areas including total area (+ 25.3%, p ≤ 0.05), trabecular area (+ 56.2%, p ≤ 0.05), and cortical perimeter (+ 10.7%, p ≤ 0.05) at the defined region of interest of 3rd DIP was significantly larger than controls. Total vBMD was 11.9% lower in PHO patients compared with the controls (p ≤ 0.05). Biochemical test results showed the increased levels of inflammatory cytokines, bone resorption markers, and joint degeneration markers in PHO patients. Serum prostaglandin PGE2, high-sensitive C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) levels were found negatively correlated with total vBMD. CONCLUSIONS: This study demonstrated higher sensitivity of the HR-pQCT measurement at DIPs by showing the differences in architecture and biomechanics parameters at DIPs between the PHO patients and healthy controls, which would be of interest clinically to investigate bone deterioration in PHO patients.

13.
Neoplasma ; 67(1): 27-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31686522

RESUMO

Noninvasive imaging methods for the diagnosis and risk stratification of pheochromocytomas (PHEOs) remain a great clinical challenge. The glucagon-like peptide-1 receptor (GLP-1R) has been validated to be overexpressed in PHEOs and therefore may be a reliable target for PHEOs. In this study, we firstly synthesized a novel radiotracer 68Ga-NOTA-MAL-Cys39-exendin-4 that specifically targets GLP-1R and evaluated the performance of GLP-1R PET for the diagnosis and risk stratification of PHEOs. Cys39-exendin-4 was conjugated to NOTA-MAL and then radiolabeled with 68Ga. The reaction was completed within 20 min with a yield of 91.6 ± 2.8%. In vitro cell uptake studies validated its high specificity. PET images showed promising tumor visualization with high uptake (1.88 ± 0.10 %ID/g for PC-12 poorly differentiated tumors and 1.09 ± 0.003 %ID/g for PC-12 highly differentiated tumors at 30min after injection). There was a significant difference in the uptake of 68Ga-NOTA-MAL-Cys39-exendin-4 between PC-12 poorly and highly differentiated tumors (p < 0.001), but no significant difference could be observed by 18F-FDG PET. Biodistribution results confirmed the findings of GLP-1R PET and demonstrated that 131I-MIBG couldn't be used for the risk stratification of PHEOs. Immunohistochemistry (IHC) staining revealed differences in GLP-1R expression between PC-12 poorly and highly differentiated tumor tissues. These results demonstrated that 68Ga-NOTA-MAL-Cys39-exendin-4 can specifically target GLP-1R with favorable pharmacokinetic properties. GLP-1R PET can be used for PHEOs detection and has potential for the risk stratification of PHEOs.

14.
Br J Dermatol ; 182(1): 85-96, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31595499

RESUMO

BACKGROUND: Dupilumab (monoclonal antibody inhibiting IL-4/IL-13 signalling) is approved for use in adolescents aged ≥ 12 years with inadequately controlled moderate-to-severe atopic dermatitis (AD). Dupilumab significantly improved AD signs/symptoms in a 16-week, randomised, placebo-controlled phase III trial in adolescents (NCT03054428). OBJECTIVES: To characterize the pharmacokinetics of dupilumab, and long-term safety and efficacy in adolescents. METHODS: This was a global, multicentre, phase IIa, open-label, ascending-dose, sequential cohort study with a phase III open-label extension (OLE) in adolescents with moderate-to-severe AD. In the phase IIa study, patients received one dupilumab dose (2 mg kg-1 or 4 mg kg-1 ) and 8 weeks of pharmacokinetic sampling. Thereafter, patients received the same dose weekly for 4 weeks, with 8-week safety follow-up. Patients then enrolled in the OLE, continuing 2 mg kg-1 or 4 mg kg-1 dupilumab weekly. Primary end points were dupilumab concentration-time profile and incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included Eczema Area and Severity Index (EASI). RESULTS: Forty adolescents received dupilumab in the phase IIa study; 36 enrolled in the OLE. Dupilumab showed nonlinear, target-mediated pharmacokinetics. Mean ± SD trough dupilumab concentrations in serum at week 48 (OLE) were 74 ± 19 mg L-1 and 161 ± 60 mg L-1 for 2 mg kg-1 and 4 mg kg-1 , respectively. Dupilumab was well tolerated over 52 weeks; the most common TEAEs were nasopharyngitis (week 52: 41% [2 mg kg-1 ], 47% [4 mg kg-1 ]) and AD exacerbation (29%, 42%). After one dupilumab dose in the phase IIa study, EASI improved from baseline to week 2 [mean ± SD reduction -34% ± 20% (2 mg kg-1 ) and -51% ± 29% (4 mg kg-1 )]. With continuing treatment, EASI scores improved further [week 52: -85% ± 12% (2 mg kg-1 ) and -84% ± 20% (4 mg kg-1 )]. CONCLUSIONS: In adolescents with moderate-to-severe AD, dupilumab's pharmacokinetic profile was similar to that in adults. These 52-week safety and efficacy data support long-term use of dupilumab in this patient population. What's already known about this topic? Adolescents with moderate-to-severe atopic dermatitis (AD) have high unmet medical need, with significant disease burden and limited treatment options. Dupilumab (monoclonal antibody against interleukin-4 receptor α) is approved for the treatment of adolescents with moderate-to-severe AD who are inadequately responsive to standard of care (U.S.A.) or candidates for systemic therapy (European Union). A 16-week, randomized, placebo-controlled phase III trial in adolescents demonstrated significant improvements in AD signs/symptoms with an acceptable safety profile. What does this study add? These studies demonstrate the long-term safety and efficacy of dupilumab in adolescents with moderate-to-severe AD for up to 52 weeks of treatment, thus extending and reinforcing the findings from the 16-week dupilumab phase III trial. The data from these studies also support the use of dupilumab in combination with current standard of care (topical corticosteroids), which was not evaluated in the 16-week phase III monotherapy trial.

16.
Lett Appl Microbiol ; 70(1): 42-47, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31642085

RESUMO

The increasing frequency of class A KPC enzymes, class B metallo-ß-lactamases (MBLs) and class D OXA-48 enzymes in Enterobacteriaceae makes their early identification urgent. A simple commercial MASTDISCS combi Carba plus disc system (MAST-Carba plus) was designed for the identification of MBLs, KPC and OXA-48 carbapenemase genes in Enterobacteriaceae. To validate the MAST-Carba plus, a total of 77 isolates of carbapenemase-producing Enterobacteriaceae (CPE) and 84 isolates of noncarbapenemase-producing Enterobacteriaceae (non-CPE) were selected for differentiation of the genes of Enterobacteriaceae by MAST-Carba plus. Meanwhile, the carbapenemase genes such as blaKPC , blaIMP , blaVIM , blaNDM-1 and blaOXA-48 were detected by PCR (polymerase chain reaction). Thus, when considered on the basis of PCR results, the sensitivity of MAST-Carba plus detection of KPC strains is 82·3%, the specificity is 100·0%, the positive predictive value is 100·0% and the negative predictive value is 92·4%. For MBLs strains, the sensitivity is 100·0%, the specificity is 97·1%, the positive predictive value is 84·6% and the negative predictive value is 100·0%. For OXA-48 strains, the sensitivity is 100·0%, the specificity is 99·4%, the positive predictive value is 80·0% and the negative predictive value is 100·0%. Our findings suggest that MAST-Carba plus is a rapid and promising method for identifying the MBLs, KPC and OXA-48 carbapenemase genes in Enterobacteriaceae, which could be exploited in basic microbiology laboratory to prevent the transmission of CPE. SIGNIFICANCE AND IMPACT OF THE STUDY: Not only detection of carbapenemases but also identification of their genes accurately and rapidly in Enterobacteriaceae is still a major challenge for clinical laboratories in order to prevent the transmission of carbapenemase-producing Enterobacteriaceae (CPE). Therefore, this study aimed to evaluate the performance of a new rapid method (MASTDISCS combi Carba plus) for the identification of metallo-ß-lactamases (MBLs), KPC and OXA-48 carbapenemase genes in Enterobacteriaceae clinical isolates.

17.
Zhonghua Nei Ke Za Zhi ; 59(1): 23-28, 2020 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-31887832

RESUMO

Objective: To investigate the association of GNA11 gene polymorphisms with the risk of adult-onset non-surgical hypoparathyroidism (Ns-HypoPT). Methods: Genotyping of GNA11 single nucleotide polymorphisms (SNPs) (rs28685098, rs4806907, rs11084997 and rs78003011) was carried out in 203 patients and 209 healthy participants by sequenom MassArray iPLEX System. These SNPs are located in promoter and 3'untranslated region (3'UTR) of GNA11 gene, respectively. Results: Allele and genotype frequencies of rs11084997 in patients were significantly different from those of controls (genotype GG:60.5% vs. 49.8%, GC: 35.5% vs. 41.6%, CC: 4.0% vs. 8.6%, P=0.038; G allele 78.3% vs. 70.6%, C allele 21.7% vs. 29.4%, P=0.012), and the C allele of rs11084997 carriers had a lower risk to develops Ns-HypoPT in additive and dominant genetic models [OR=0.382 (0.160-0.915), 0.647 (0.437-0.957)]. CC-Haplotype formed by the minor alleles of rs4806907 and rs11084997 was associated with a decreased risk of Ns-HypoPT in additive, dominant and recessive genetic model [OR=0.317 (0.126-0.801), 0.640 (0.430-0.952), 0.367 (0.148-0.912)]. Conclusion: The minor allele C of rs11084997 in GNA11 gene promoter was associated with decreased risk of Ns-HypoPT in Chinese population.


Assuntos
Subunidades alfa de Proteínas de Ligação ao GTP/genética , Predisposição Genética para Doença , Hipoparatireoidismo/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , China , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Frequência do Gene , Genótipo , Humanos , Hipoparatireoidismo/diagnóstico , Polimorfismo de Nucleotídeo Único
18.
Zhonghua Nei Ke Za Zhi ; 59(1): 58-61, 2020 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-31887838

RESUMO

The purpose of this study is to investigate the matrix metalloproteinase-3 (MMP-3) levels in patients with systemic lupus erythematosus (SLE) and its significance in identifying disease activity and pulmonary infections. A total of 122 SLE patients were enrolled, including 21 with pulmonary infections, 16 with arthritis, 26 with nephritis, 10 with vasculitis, and 23 healthy controls. Serum MMP-3, C-reactive protein (CRP), serum amyloid A (SAA), and haptoglobin (HPT) levels were measured in all subjects. The results showed that the levels of MMP-3 in SLE combined with pulmonary infections [(230.10±44.92) µg/L], arthritis [(140.20±20.76) µg/L], nephritis [(155.40±23.36) µg/L] were higher than those in SLE only [(91.74±10.47) µg/L]. The levels of MMP-3 [(210.30±45.71) µg/L], CRP [(12.11±5.21) mg/L], HPT [(1.57±0.23) g/L] in active SLE combined with pulmonary infections were higher than those inactive SLE without pulmonary infections including MMP-3 [(124.00±15.22) µg/L], CRP [(7.76±2.96) mg/L], HPT [(0.89±0.09) g/L]. The levels of CRP [(10.03±2.70) mg/L], SAA [(89.22±36.77) mg/L] in active SLE with pulmonary infections and CRP[(7.76±2.96) mg/L], SAA [(60.22±19.7) mg/L] in active SLE without pulmonary infections were higher than CRP [(1.90±0.39) mg/L], SAA [(17.60±3.89) mg/L] in stable SLE with pulmonary infections. It suggests that the levels of CRP and SAA are elevated in active SLE with pulmonary infections. Serum MMP-3 in combination with CRP may assist in differentiating from SLE pulmonary infections.


Assuntos
Artrite , Lúpus Eritematoso Sistêmico , Metaloproteinase 3 da Matriz/metabolismo , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Humanos
19.
Plant Biol (Stuttg) ; 22 Suppl 1: 143-152, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30597713

RESUMO

Plastid casein kinase 2 (CK2), which is a major Ser/Thr-specific enzyme in higher organisms, plays an essential role in plant development and diverse abiotic stresses. CKB1 is a regulatory subunit beta of CK2. To expand our understand of functions of the CKB1 gene in Arabidopsis thaliana, protein changes among wild-type (WT) and CKB1 gain- and loss-of-function mutants were compared. Proteins extracted from the CKB1 knockout mutant and overexpressing mutant were compared with Col-0 plants using 2D-PAGE. Proteins regulated by CKB1 were identified with matrix-assisted laser desorption ionisation time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF), and its transcript was verified by qRT-PCR. Bioinformatics analysis, including gene ontology and protein-protein interaction analysis, were employed. The results of mass spectra and bioinformatics analysis suggest that CKB1 may have functions in regulation of the ribosomal protein L10 (RPL10) family and is involved in ultraviolet-B (UV-B) response. Furthermore, qRT-PCR verification showed CKB1 expression was up-regulated by UV-B stress. The expression levels of five genes in the RPL10 family were reduced in the ckb1 T-DNA insertion mutants, whereas they increased in the CKB1 overexpressing mutants under both normal conditions and UV-B treatment. In conclusion, CKB1 has important functions in UV-B radiation stress. Our study implies that CKB1 positively regulates UV-B radiation stress signalling, possibly through modulating expression of the RPL10 family.

20.
J Appl Microbiol ; 128(1): 54-64, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31562827

RESUMO

AIM: The aim of this study was to investigate the effects of dietary supplementation of Rhodotorula mucilaginosa solid-state fermentation product (RSFP) on the laying performance, egg quality and intestinal microbial flora of hens. METHODS AND RESULTS: In this study, 40-week-old Roman laying hens (n = 216) were randomly assigned to one of the four groups: the control (CON) group, fed 87.5% basal diet +12.5% fermentation substrate; the 0.5% RSFP group, fed 87.5% basal diet +12.0% fermentation substrate +0.5% RSFP; the 2.5% RSFP group, fed 87.5% basal diet +10.0% fermentation substrate +2.5% RSFP; and the 12.5% RSFP group, fed 87.5% basal diet +12.5% RSFP. The effect of each treatment was analysed in six replicates of nine hens. The experimental period was 31 days, which included a 3-day adaptation period. After 31 days of feeding, one hen from each replicate was randomly selected and killed, and the jejunum and digesta in the cecum were collected for the determination of the intestinal morphology and microbial flora respectively. Daily egg mass in the 2.5 and 12.5% RSFP groups and egg production and feed conversion ratio in the 12.5% RSFP group were higher than those in control group (P < 0.05). The yolk colour was improved in hens fed RSFP-supplemented diets (P < 0.05). Hens fed RSFP-supplemented diet showed a decrease in the relative abundances of Proteobacteria, Bacteroides, Helicobacteraceae, Helicobacter and Lachnospiraceae UCG-002, but an increase in the relative abundance of Prevotellaceae UCG-001 in the cecum (P < 0.05). CONCLUSION: Dietary RSFP supplementation improved the laying performance, egg quality and intestinal microflora of hens. SIGNIFICANCE AND IMPACT OF THE STUDY: Dietary supplementing diet with Rhodotorula mucilaginosa solid-state fermentation product, which is rich in carotenoids, improved the yolk colour and increased the carotenoid content, thereby improving the intestinal health of hens.

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