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1.
Front Cell Infect Microbiol ; 11: 652837, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33869084

RESUMO

Disturbance in microbiota affects the mucosal immune response, and it is gradually recognized to be associated with the Immunoglobin A nephropathy (IgAN). This study aims to explore the potential roles of oral microbiota in disease pathogenesis. Saliva samples were collected from 31 patients with IgAN and 30 controls for 16S rRNA gene sequencing. The evenness, diversity, and composition of oral microbiota were analyzed. Moreover, sub-phenotype association analysis was conducted. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to investigate microbiota functions. Compared to healthy controls, microbial diversity tended to decrease in IgAN, and the microbial profiles were remarkably distinguished. The relative abundance of Capnocytophaga and SR1_genera_incertae_sedis were enriched, whereas 17 genera, such as Rothia, were significantly reduced in IgAN. Variable importance in projection scores showed that 12 genera, including Capnocytophaga, Rothia, and Haemophilus, could discriminate between the two groups. In the sub-phenotype correlation analysis, the relative abundance of Capnocytophaga and Haemophilus was positively associated with levels of proteinuria and serum IgA, respectively. Further metabolic pathway analysis showed 7 predictive functional profiles, including glycosphingolipid biosynthesis, oxidative phosphorylation, and N-glycan biosynthesis were enriched in IgAN. In conclusion, disturbance in oral microbiota was observed to be associated with IgAN and its sub-phenotypes, which may shed novel insights into disease pathogenesis from a microbiome perspective.

2.
Front Immunol ; 12: 600598, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717080

RESUMO

C-C chemokine receptor 6 (CCR6) is a susceptibility gene of various immune-related diseases, which was suggested to be shared with immunoglobulin A nephropathy (IgAN). In this study, we aimed to identify the functional variants. First, we analyzed the associations of CCR6 common and rare variants detected by multi-platform chips with IgAN susceptibility using imputation and identified 68 significantly associated common variants located in the regulatory region. Among them, rs3093023 showed both statistical significance (rs3093023-A, odds ratio [OR] = 1.15, P = 2.00 × 10-2) and the expression quantitative trait loci (eQTL) effect (P = 1.45 × 10-3). It was independently replicated (rs3093023-A, OR = 1.18, P = 5.56 × 10-3) and the association was reinforced in the meta-analysis (rs3093023-A, OR = 1.17, P = 6.14 × 10-7). Although rs3093023 was in a strong linkage disequilibrium with the reported CCR6 functional variant dinucleotide polymorphism, CCR6DNP, the alleles of rs3093023 (G>A) rather than of CCR6DNP were shown differential nuclear protein binding effect by electrophoretic mobility shift assay. The RegulomeDB and JASPAR databases predicted Pou2f1 as the potential transcription factor, which was negatively associated with CCR6 mRNA (r = -0.60, P = 3.94 × 10-9). At the mRNA level, the eQTL effect of CCR6 was validated (P = 4.39 × 10-2), and CCR6 was positively associated with the expression of CCR4 and IL-17A rather than that of CXCR3 and IFNG. At the protein level, a higher CCR6+ cell ratio was observed in a risk allele dose-dependent manner in lymphocytes (P = 3.57 × 10-2), CD3+ T cells (P = 4.54 × 10-2), and CD4+ T cells (P = 1.32 × 10-2), but not in CD8+ T cells. Clinical-pathological analysis showed that rs3093023 risk allele was significantly associated with diastolic blood pressure, serum creatinine, and high ratio of tubular atrophy/interstitial fibrosis. Overall, the rs3093023 was prioritized as the function variant in CCR6, which may contribute to IgAN susceptibility by regulating Th17 cells.

3.
J Am Soc Nephrol ; 32(3): 545-552, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33593824

RESUMO

BACKGROUND: Galactose-deficient IgA1 plays a key role in the pathogenesis of IgA nephropathy, the most common primary GN worldwide. Although serum levels of galactose-deficient IgA1 have a strong genetic component, the genetic link between this molecule and IgA nephropathy has not yet been clearly established. METHODS: To identify novel loci associated with galactose-deficient IgA1, we performed a quantitative genome-wide association study for serum galactose-deficient IgA1 levels, on the basis of two different genome-wide association study panels conducted in 1127 patients with IgA nephropathy. To test genetic associations with susceptibility to IgA nephropathy, we also enrolled 2352 patients with biopsy-diagnosed IgA nephropathy and 2632 healthy controls. Peripheral blood samples from 59 patients and 27 healthy controls were also collected for gene expression analysis. RESULTS: We discovered two loci, in C1GALT1 and GALNT12, that achieved genome-wide significance, explaining about 3.7% and 3.4% of variance in serum galactose-deficient IgA1 levels, respectively. We confirmed the previously reported association of C1GALT1 with serum galactose-deficient IgA1 levels, but with a different lead single-nucleotide polymorphism (rs10238682; ß=0.26, P=1.20×10-9); the locus we identified at GALNT12 (rs7856182; ß=0.73, P=2.38×10-9) was novel. Of more interest, we found that GALNT12 exhibits genetic interactions with C1GALT1 in both galactose-deficient IgA1 levels (P=1.40×10-2) and disease risk (P=6.55×10-3). GALNT12 mRNA expression in patients with IgA nephropathy was significantly lower compared with healthy controls. CONCLUSIONS: Our data identify GALNT12 as a novel gene associated with galactose-deficient IgA1 and suggest novel genetic interactions. These findings support a key role of genetically conferred dysregulation of galactose-deficient IgA1 in the development of IgA nephropathy.

4.
J Nephrol ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591553

RESUMO

BACKGROUND: Hydroxychloroquine (HCQ) has been used as a supportive therapy for IgA nephropathy (IgAN). We aimed to determine the long-term efficacy and safety of HCQ therapy in patients with IgAN. METHODS: A total of 180 patients with IgAN who had received HCQ therapy for at least 1 year were enrolled in this study. The changes in proteinuria and the estimated glomerular filtration rate (eGFR) were analyzed during the follow-up period. RESULTS: The level of proteinuria decreased from 1.69 [1.24, 2.30] to 1.01 [0.59, 1.74] g/day (- 37.58 [- 57.52, 8.24] %, P < 0.001) at 12 months and to 1.00 [0.59, 1.60] g/day (- 55.30 [- 71.09, - 3.44] %, P < 0.001) at 24 months. There was no significant change in the eGFR of these patients at 12 months (65.82 ± 25.22 vs. 63.93 ± 25.96 ml/min/1.73 m2, P = 0.411); however, the eGFR decreased from 65.82 ± 25.22 to 62.15 ± 25.81 ml/min/1.73 m2 at 24 months (P = 0.003). The cumulative frequency of all patients with a 50% decrease in proteinuria was 72.78% at 12 months. Sixty (33.3%) patients changed to corticosteroid therapy during the follow-up period. No serious adverse effects were documented during HCQ treatment. CONCLUSIONS: HCQ effectively and safely reduces proteinuria in IgAN patients with different levels of eGFR, supporting the maintenance of stable kidney function in the long term.

5.
Clin J Am Soc Nephrol ; 16(2): 213-224, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33462083

RESUMO

BACKGROUND AND OBJECTIVES: IgA nephropathy is the most common form of primary GN worldwide. The evidence of geographic and ethnic differences, as well as familial aggregation of the disease, supports a strong genetic contribution to IgA nephropathy. Evidence for genetic factors in IgA nephropathy comes also from genome-wide association patient-control studies. However, few studies have systematically evaluated the contribution of coding variation in IgA nephropathy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a two-stage exome chip-based association study in 13,242 samples, including 3363 patients with IgA nephropathy and 9879 healthy controls of Han Chinese ancestry. Common variant functional annotation, gene-based low-frequency variants analysis, differential mRNA expression, and gene network integration were also explored. RESULTS: We identified three non-HLA gene regions (FBXL21, CCR6, and STAT3) and one HLA gene region (GABBR1) with suggestive significance (P meta <5×10-5) in single-variant associations. These novel non-HLA variants were annotated as expression-associated single-nucleotide polymorphisms and were located in enhancer regions enriched in histone marks H3K4me1 in primary B cells. Gene-based low-frequency variants analysis suggests CFB as another potential susceptibility gene. Further combined expression and network integration suggested that the five novel susceptibility genes, TGFBI, CCR6, STAT3, GABBR1, and CFB, were involved in IgA nephropathy. CONCLUSIONS: Five novel gene regions with suggestive significance for IgA nephropathy were identified and shed new light for further mechanism investigation.

6.
Kaohsiung J Med Sci ; 37(4): 276-285, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33332731

RESUMO

MicroRNAs (miRNAs) are dysregulated in human ovarian carcinoma (OC). But the mechanism underlying miR-10a-5p in regulating the progression of OC need deeply explored. In the current study, we observed that miR-10a-5p was down-expressed in OC samples and OC cell lines. In addition, miR-10a-5p restrained the viability, colony formation, migration ability and invasiveness of OC cells. We further ascertained Homeobox A1 (HOXA1) was a downstream gene of miR-10a-5p. Furthermore, HOXA1 was distinctly upregulated in OC samples. Finally, upregulation of HOXA1 abolished the suppressive effects of miR-10a-5p on OC cells. These observations suggested that miR-10a-5p suppressed the aggressive phenotypes of OC cells via regulating HOXA1.

7.
BMC Nephrol ; 21(1): 469, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172397

RESUMO

BACKGROUND: Hydroxychloroquine (HCQ) is a well-known immunomodulator that was recently used in immunoglobulin A (IgA) nephropathy (IgAN) due to its antiproteinuric effects. We investigated the effects of HCQ in patients with IgAN whose proteinuria remained above 1 g/d after conventional immunosuppressive (IS) therapy. METHODS: This study was a retrospective case-control study. Twenty-six patients with IgAN who received HCQ and had insufficient responses to IS therapy (corticosteroid (CS) therapy with/without IS agents) were included. Twenty-six matched historical controls who received conventional IS therapy were selected using propensity score matching. The clinical data from 6 months were compared. RESULTS: Proteinuria at baseline was comparable between the "IS therapy plus HCQ" and "conventional IS therapy" groups (2.35 [interquartile range (IQR), 1.47, 2.98] vs. 2.35 [IQR, 1.54, 2.98] g/d, p = 0.920). A significant reduction in proteinuria was noted in IgAN patients with HCQ treatment (2.35 [IQR, 1.47, 2.98] vs. 1.10 [IQR, 0.85, 1.61] g/d, p = 0.002). The percent reduction in proteinuria at 6 months was similar between the two groups (- 39.81% [- 66.26, - 12.37] vs. -31.99% [- 67.08, - 9.14], p = 0.968). The cumulative frequency of patients with a 50% reduction in proteinuria during the study was also comparable between the two groups (53.8% vs. 57.7%, p = 0.780). No serious adverse events (SAEs) were observed during the study. CONCLUSIONS: Use of HCQ achieved has similar reduction in proteinuria compared to conventional IS therapy in patients with IgAN who had insufficient responses to IS therapy.

8.
Ann Transl Med ; 8(17): 1053, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33145272

RESUMO

Background: The aim of the study was to identify the clinical features and the factors associated with burn induced mortality among young adults after exposure to indoor explosion and fire. Methods: This is an observational study which included burn patients who were admitted to eighteen ICUs after a fire disaster. Epidemiologic and clinical characteristics, as well as therapy were recorded. The primary outcome was 90-day mortality. The mortality-related factors were also analyzed. Results: There were 167 burn patients enrolled in the study, the median age was 38 years, 62 (37.1%) patients died within 90 days. Seventy-one percent of patients had a burn size ≥90% TBSA, and 73.7% of patients had a full-thickness burn area above 50% TBSA. The survivors had lower Baux scores, and received earlier escharectomy and autologous skin grafts. The 50% mortality rates (LA50s) for burn size and full-thickness burn area were 95.8% and 88.6% TBSA, respectively. The multivariate analysis showed that full-thickness burn area over 50% TBSA and residual burned surface area (RBSA)/TBSA at 28 days were strong predictors of mortality among burn patients (odds ratio 2.55; 95% CI, 1.01 to 6.44, P=0.047; odds ratio 1.07; 95% CI, 1.04 to 1.09, P<0.001). The ROC curve-based cut-off values of RBSA/TBSA at 28 days for predicting 90-day mortality were 62.5%. Conclusions: Burn size and full-thickness burn area were the main risk factors for poor outcome in patients with extensive burns. Earlier escharectomy and autologous skin grafts may improve outcomes.

9.
ScientificWorldJournal ; 2020: 8364250, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061862

RESUMO

[This corrects the article DOI: 10.1155/2014/432318.].

10.
Sleep Breath ; 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33128178

RESUMO

OBJECTIVE: To explore the effect of minimally invasive surgical treatment on the sleep quality and work ability of patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Fifty-one patients who underwent minimally invasive surgery in the Sleep Respiratory Disease Diagnostic and Treatment Center of the West China Fourth Hospital of Sichuan University from January 2017 to January 2019 were selected as study subjects. All subjects completed polysomnography monitoring (PSG), an Epworth sleepiness scale (ESS), and a work ability index (WAI) before and 1 year after the minimally invasive surgery so that the changes could be compared. RESULTS: (1) The apnea-hypopnea index (AHI), microarousal index (MAI), ESS, longest duration of apnea, and longest duration of hypoventilation in OSAHS patients decreased, while the lowest blood oxygen saturation (LsaO2) increased after minimally invasive surgery. The differences were statistically significant (p < 0.05). (2) The WAI questionnaire score increased from (37.76 ± 4.46) to (40.00 ± 4.53) after minimally invasive surgery (P < 0.05). (3) The change in the WAI questionnaire score after minimally invasive surgery was influenced by the occupational category and the change in ESS. CONCLUSION: Minimally invasive surgical treatment shows significant benefit in improving the sleep quality and working ability of patients with OSAHS.

11.
Zhongguo Gu Shang ; 33(8): 757-60, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32875768

RESUMO

OBJECTIVE: To analyze the clinical application value of adjustable skin retractor in large area of limb wound defect in children. METHODS: From January 2017 to January 2019, 11 children including 9 males and 2 females, aged 4 to 12 (8.3±2.7) years old with severe lower extremity wound defects were treated with adjustable skin stretch and closure device, all of them were unilateral lower extremity large area wound defects, including 4 cases of limb skin defect caused by traffic accident, 3 cases of failure to close after osteofasciotomy and decompression, 3 cases of plate exposure after internal fixation of lower extremity fracture and 1 case of ischemic necrosis after debridement and suturing of skin avulsion. The width of the wound was (5.6±1.2) cm and the length was (7.0±1.6) cm. VSD negative pressure drainage and expanded suture were used in all the patients. Four of them had been treated with free skin graft and two had been treated with local flap transfer. The graft or flap operation failed, and the effect of the early treatment was not good. RESULTS: After 5 to 14 (10.5±2.6) days of continuous traction, the wound was closed and no skin grafting or flap repair was performed. No complications such as poor blood supply, skin infection and necrosis, peripheral sensory disturbance occurred. All 11 patients were followed up for 3 to 18 (8.9±3.8) months. The wound edge skin was linear healing with slight scar. CONCLUSION: It is in accordance with Wolff's law and the concept of natural tissue reconstruction to treat large-scale limb wound defects in children with adjustable skin stretch and closure device, which provides an effective method for the treatment of limb skin and soft tissue defects in children.


Assuntos
Procedimentos Cirúrgicos Reconstrutivos , Lesões dos Tecidos Moles/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Transplante de Pele , Resultado do Tratamento , Cicatrização
12.
Bioorg Med Chem Lett ; 30(16): 127286, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32631508

RESUMO

Natural quinones and their analogues have attracted growing attention because of their novel anticancer activities. A series of novel isothiazoloquinoline quinone analogues were synthesized and evaluated for antitumor activities against four different kind of cancer cells. Among them, isothiazoloquinolinoquinones inhibited cancer cells proliferation effectively with IC50 values in the nanomolar range, and isothiazoloquinolinoquinone 13a induced the cell apoptosis. Further exploration of possible mechanism of action indicates that 13a not only activates ROS production through NQO1-directed redox cycling but also inhibits the phosphorylation of STAT3. These findings indicate that 13a has potential use for the development of new skeleton drug candidate as an efficient substrate of NQO1 and STAT3 inhibitor.

13.
Front Microbiol ; 11: 1192, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655516

RESUMO

Members of the genus Metallosphaera are widely found in sulfur-rich and metal-laden environments, but their physiological and ecological roles remain poorly understood. Here, we sequenced Metallosphaera tengchongensis Ric-A, a strain isolated from the Tengchong hot spring in Yunnan Province, China, and performed a comparative genome analysis with other Metallosphaera genomes. The genome of M. tengchongensis had an average nucleotide identity (ANI) of approximately 70% to that of Metallosphaera cuprina. Genes sqr, tth, sir, tqo, hdr, tst, soe, and sdo associated with sulfur oxidation, and gene clusters fox and cbs involved in iron oxidation existed in all Metallosphaera genomes. However, the adenosine-5'-phosphosulfate (APS) pathway was only detected in Metallosphaera sedula and Metallosphaera yellowstonensis, and several subunits of fox cluster were lost in M. cuprina. The complete 3-hydroxypropionate/4-hydroxybutyrate cycle and dicarboxylate/4-hydroxybutyrate cycle involved in carbon fixation were found in all Metallosphaera genomes. A large number of gene family gain events occurred in M. yellowstonensis and M. sedula, whereas gene family loss events occurred frequently in M. cuprina. Pervasive strong purifying selection was found acting on the gene families of Metallosphaera, of which transcription-related genes underwent the strongest purifying selection. In contrast, genes related to prophages, transposons, and defense mechanisms were under weaker purifying pressure. Taken together, this study expands knowledge of the genomic traits of Metallosphaera species and sheds light on their evolution.

15.
J Dermatolog Treat ; : 1-5, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32431191

RESUMO

Background: Tacrolimus is a new type immunosuppressant. The aim of this study was to evaluate the effectiveness of topical tacrolimus 0.1% ointment at 2 different frequencies in treating patients with exfoliative cheilitis.Methods: A total of 40 patients with exfoliative cheilitis were randomly divided into the QD group receiving topical tacrolimus 0.1% ointment once a day or the QOD group receiving topical tacrolimus 0.1% ointment once-two-day. Patients were also applied wet dressing of saline twice a day. The effectiveness of treatment was defined as the percentage of improvement in signs or symptoms.Results: 37 patients completed the 2-week treatment. And, a full set was analyzed. The effectiveness of topical tacrolimus 0.1% ointment for relief in objective sign and subjective symptom was 50% and 67.5%% in the QD group, respectively. For the QOD group, the effectiveness of sign and symptom relief was 50% and 73.5%. There was no significant difference of effectiveness between application topical tacrolimus once a day and once 2 days.Conclusion: Our data suggested that application of topical tacrolimus 0.1% ointment once a day and once 2 days had similar clinical effectiveness for sign and symptom relief in patients with exfoliative cheilitis.

16.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(2): 155-159, 2020 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-32314888

RESUMO

OBJECTIVE: This work aimed to evaluate the effect of different surface treatments on the shear bond strength of resin nano ceramic to resin cement, thereby providing a theoretical basis for the improvement of clinical application. METHODS: A total of 150 specimens (10 mm×10 mm×3 mm) were milled from resin nano ceramic blocks (Lava Ultimate) using computer-aided design/computer aided manufacturing(CAD/CAM) technology. The specimens were randomly divided into five groups according to the surface treatment performed, as follows: control, sandblasted, sandblasted+silane, hydrofluoric acid, and hydrofluoric acid+silane groups. After the corresponding surface treatment, the specimens were cemented using Single Bond Universal Adhesive and RelyXTM Ultimate ClickerTM adhesive resin cement. All cemented specimens were placed in distilled water for 24 h and 30 days and subjected to a shear bond strength test in a universal testing machine. RESULTS: The surface treatment and water storage periods showed significant effects on bond strength. Surface treatment with sandblasted+silane showed the highest shear strength values among all tested groups, and the difference was statistically significant (P<0.05). A difference was observed between the control and hydrofluoric acid groups, and both had significantly difference compared with other groups (P<0.05). Sandblasted and hydrofluoric acid+silane groups were not statistically different, and both had significantly difference compared with other groups (P<0.05). CONCLUSIONS: The surface of resin nanoceramic treated by sand-blasted, sandblasted+silane, and hydrofluoric acid+silane can improve the bond strength. The sandblasted+silane group had the best the shear bond strength among the groups.


Assuntos
Colagem Dentária , Cimentos de Resina , Cerâmica , Porcelana Dentária , Análise do Estresse Dentário , Teste de Materiais , Resistência ao Cisalhamento , Silanos , Propriedades de Superfície
17.
Bioorg Med Chem Lett ; 30(9): 127047, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32139325

RESUMO

A series of DLC (delocalized lipophilic cation) modified spinosyn derivatives were synthesized and evaluated for antitumor efficacies both in vitro and in vivo. Cancer cell based antiproliferative assays indicated that the more lipophilic derivatives had stronger inhibitory effects on the tested cancer cell lines. Compound 7b and 8b exhibited strong anti-OXPHOS and apoptosis inducing ability. Notable antitumor efficacies of 7b (5 mg/kg) and 8b (2.5 mg/kg) were observed in the in vivo tumor xenograft experiments, however, lethal toxicities were observed on higher dosages. Our findings indicated that DLC modification is a viable strategy to enhance the anti-OXPHOS and antitumor efficacies of spinosyn derivatives.

18.
Am J Kidney Dis ; 76(1): 90-99, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32197881

RESUMO

RATIONALE & OBJECTIVE: Hematuria is the most typical presentation of immunoglobulin A nephropathy (IgAN); however, its role in disease progression is still controversial. This study aimed to evaluate the association of hematuria and progression of IgAN. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A cohort of 1,333 patients with IgAN treated at a Chinese referral hospital with a median follow-up of 45 months. PREDICTORS: Microhematuria was evaluated in fresh urine using a fully automated urine particle analyzer (automated method) and urine sediment examination by a skilled examiner (manual method). Hematuria was characterized as a time-varying attribute; namely, average hematuria level was calculated for every 6-month period for each patient during follow-up. Remission was defined as average red blood cell count ≤5/high-power field (manual method) or ≤28 red blood cells/µL (automated method) during the first 6 months of follow-up. OUTCOMES: Composite event of 50% decline in estimated glomerular filtration rate or development of kidney failure. ANALYTICAL APPROACH: Multivariable cause-specific hazards models to analyze the relationship between hematuria and the composite kidney disease progression event. RESULTS: Time-varying hematuria during follow-up was an independent risk factor for the composite kidney disease progression event (HR, 1.46; 95% CI, 1.13-1.87; P = 0.003). Hematuria remission during the 6 months after diagnosis was associated with a significantly lower rate of the composite kidney disease progression event (HR, 0.41; 95% CI, 0.28-0.61; P < 0.001). A significant interaction was detected between remission of proteinuria and remission of hematuria during the first 6 months (P < 0.001). The association between remission of hematuria and kidney disease progression was detectable (HR, 0.46; 95% CI, 0.32-0.68) within the subpopulation with persistent proteinuria (protein excretion > 1.0 g/d during the first 6 months), but not among patients whose proteinuria had remitted (HR, 0.64; 95% CI, 0.31-1.29; P = 0.2). The 2 techniques for hematuria evaluation were strongly and significantly linearly correlated (r = 0.948; P < 0.001), and results using these 2 methods were consistent. LIMITATIONS: A single-center retrospective study. Proportional hazards regression incorporating time-varying covariates may create time-varying confounding. The predictive value of reductions in hematuria was not directly evaluated. CONCLUSIONS: Level of hematuria was independently associated with kidney disease progression, whereas hematuria remission was associated with improved kidney outcomes in IgAN among patients with persistent proteinuria. Additionally, to monitor IgAN progression, automated methods to evaluate hematuria hold promise as a replacement for manual evaluation of urinary sediment.


Assuntos
Progressão da Doença , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/epidemiologia , Hematúria/diagnóstico , Hematúria/epidemiologia , Adulto , Estudos de Coortes , Feminino , Seguimentos , Glomerulonefrite por IGA/sangue , Hematúria/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal/sangue , Insuficiência Renal/diagnóstico , Insuficiência Renal/epidemiologia , Estudos Retrospectivos
19.
Insect Sci ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32091660

RESUMO

Fruit flies usually harbor diverse communities of bacteria in their digestive systems, which are known to play a significant role in their fitness. However, little information is available on Zeugodacus tau, a polyphagous pest worldwide. This study reports the first extensive analysis of bacterial communities in different life stages and their effect on the development and reproduction of laboratory-reared Z. tau. Cultured bacteria were identified using the conventional method, and all bacteria were identified by high-throughput technologies (16S ribosomal RNA gene sequencing of V3-V4 region). A total of six bacterial phyla were identified in larvae, pupae, and male and female adult flies, which were distributed into 14 classes, 32 orders, 58 families and 96 genera. Proteobacteria was the most represented phylum in all the stages except larvae. Enterobacter, Klebsiella, Providencia, and Pseudomonas were identified by conventional and next-generation sequencing analysis in both male and female adult flies, and Enterobacter was found to be the main genus. After being fed with antibiotics from the first instar larvae, bacterial diversity changed markedly in the adult stage. Untreated flies laid eggs and needed 20 days before oviposition while the treated flies showed ovary development inhibited and were not able to lay eggs, probably due to the alteration of the microbiota. These findings provide the cornerstone for unexplored research on bacterial function in Z. tau, which will help to develop an environmentally friendly management technique for this kind of harmful insect.

20.
Chin Med J (Engl) ; 133(3): 277-284, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31929371

RESUMO

BACKGROUND: High levels of plasma homocysteine occur almost uniformly in patients with end-stage renal disease (ESRD). IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and a common cause of ESRD in young adults. Here, we aimed to detect whether homocysteine was elevated and associated with clinical-pathologic manifestations of IgAN patients and tested its causal effects using a two-sample Mendelian randomization (MR) approach. METHODS: For observational analysis, 108 IgAN patients, 30 lupus nephritis (LN) patients, 50 minimal change disease (MCD) patients, and 206 healthy controls were recruited from April 2014 to April 2015. Their plasma homocysteine was measured and clinical-pathologic manifestations were collected from medical records. For MR analysis, we further included 1686 IgAN patients. The missense variant methylenetetrahydrofolate reductase C677T (rs1801133) was selected as an instrument, which was genotyped by TaqMan allele discrimination assays. RESULTS: Majority of IgAN patients (93.52%, 101/108) showed elevated levels of plasma homocysteine (>10 µmol/L). Plasma homocysteine in IgAN patients was significantly higher than that in MCD patients (median: 18.32 vs. 11.15 µmol/L, Z = -5.29, P < 0.01) and in healthy controls (median: 18.32 vs. 10.00 µmol/L, Z = -8.76, P < 0.01), but comparable with those in LN patients (median: 18.32 L vs. 14.50 µmol/L, Z = -1.32, P = 0.19). Significant differences were observed in sub-groups of IgAN patients according to quartiles of plasma homocysteine for male ratio (22.22% vs. 51.85% vs. 70.37% vs. 70.37%, χ = 14.29, P < 0.01), serum creatinine (median: 77.00 vs. 100.00 vs. 129.00 vs. 150.00 µmol/L, χ = 34.06, P < 0.01), estimated glomerular filtration rate (median: 100.52 vs. 74.23 vs. 52.68 vs. 42.67 mL·min·1.73 m, χ = 21.75, P < 0.01), systolic blood pressure (median: 120.00 vs. 120.00 vs. 125.00 vs. 130.00 mmHg, χ = 2.97, P = 0.05), diastolic blood pressure (median 80.00 vs. 75.00 vs. 80.00 vs. 81.00 mmHg, χ = 11.47, P < 0.01), and pathologic tubular atrophy and interstitial fibrosis (T) (T0/T1/T2: 62.96%/33.33%/3.70% vs. 29.63%/40.74%/29.63% vs. 24.00%/48.00%/28.00% vs. 14.81%/37.04%/48.15%, χ = 17.66, P < 0.01). The coefficient of each rs1801133-T allele on homocysteine levels after controlling age and sex was 7.12 (P < 0.01). MR estimates showed causal positive effects of homocysteine on serum creatine (ß = 0.76, P = 0.02), systolic blood pressure (ß = 0.26, P = 0.02), diastolic blood pressure (ß = 0.20, P = 0.01), and pathologic T lesion (ß = 0.01, P = 0.01) in IgAN. CONCLUSIONS: By observational and MR analyses, consistent results were observed for associations of plasma homocysteine with serum creatinine, blood pressures, and pathologic T lesion in IgAN patients.


Assuntos
Glomerulonefrite por IGA/sangue , Homocisteína/sangue , Análise da Randomização Mendeliana , Adulto , Pressão Sanguínea , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/patologia , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade
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