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1.
Enzyme Microb Technol ; 141: 109667, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33051017

RESUMO

A number of organic synthesis involve threonine aldolase (TA), a pyridoxal phosphate (PLP)-dependent enzyme. Although the addition of exogenous PLP is necessary for the reactions, it increases the cost and complicates the purification of the product. This work constructed a PLP self-sufficient biocatalysis system for TA, which included an improvement of the intracellular PLP level and co-immobilization of TA with PLP. Engineered strain BL-ST was constructed by introducing PLP synthase PdxS/T to Escherichia coli BL21(ED3). The intracellular PLP concentration of the strain increased approximately fivefold to 48.5 µmol/gDCW. l-TA, from Bacillus nealsonii (BnLTA), was co-expressed in the strain BL-ST with PdxS/T, resulting in the engineered strain BL-BnLTA-ST. Compared with the control strain BL-BnLTA (254.1 U/L), the enzyme activity of the strain BL-BnLTA-ST reached 1518.4 U/L without the addition of exogenous PLP. An efficient co-immobilization system was then designed. The epoxy resin LX-1000HFA wrapped by polyethyleneimine (PEI) acted as a carrier to immobilize the crude enzyme solution of the strain BL-BnLTA-ST mixed with an extra 100 µM of exogenous PLP, resulting in the catalyst HFAPEI-BnLTA-STPLP 100. HFAPEI-BnLTA-STPLP 100 exhibited a half-life of approximately 450 h, and the application of the catalyst in the continuous biosynthesis of 3-[4-(methylsulfonyl) phenyl] serine had more than 180 batch reactions (>60%conv) without the extra addition of exogenous PLP. The excellent compatibility and stability of the system were further confirmed by other TAs. This work introduced a PLP self-sufficient biocatalysis system that can reduce the cost of PLP and contribute to the industrial application of TA. In addition, the system may also be applied in other PLP-dependent enzymes.

2.
FASEB J ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33089923

RESUMO

Postischemic acute kidney injury (AKI) is a common clinical complication and often fatal, with no effective treatment available. Little is known about the role of leukocytes trapped in renal vessels during ischemia-reperfusion injury (IRI) in the postischemic AKI. We designed a new animal model in rats with preforming renal artery lavage prior to IRI to investigate the effect of diminishing the residual circulating leukocytes on kidney damage and inflammation. Moreover, the functional changes of macrophages in hypoxia reoxygenation condition were also analyzed. We found pre-ischemic renal lavage significantly decreased the serum creatinine and blood urea nitrogen levels, and downregulated the mRNA and protein expressions in kidneys and urinary secretion of kidney injury molecule-1 of rats after IRI. The renal pathological damage caused by IRI was also ameliorated by pre-ischemic renal lavage, as evidenced by fewer cast formation, diminished morphological signs of AKI in the tissue at 24 hours after IRI. Pre-ischemic renal lavage reduced the numbers of infiltrating CD68+ macrophages and MPO+ neutrophils. The mRNA expression of pro-inflammatory mediator in IRI kidneys and the levels of pro-inflammatory cytokines in circulatory system and urine were also reduced due to pre-ischemic lavage. Compared with nontreated rats with IRI, pre-ischemic renal lavage significantly reduced the phosphorylation levels of ERK and p65 subunit of NF-κB in the kidney after IRI. In addition, we found hypoxia/reoxygenation could promote the expression of pro-inflammatory mediators and inhibit the expression of anti-inflammatory factors by regulating ERK/NF-κB signaling pathway. Thus, pre-ischemic renal lavage could clearly reduce the renal damage after IRI by attenuating inflammation, and macrophages trapped in renal vessels during IRI could be important pathogenic factors driving tissue injury.

3.
Biomaterials ; 265: 120416, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-33007612

RESUMO

Hepatocellular carcinoma (HCC) is one of the most lethal tumors worldwide. This study aims to address the lack of faithful and available in vitro models for patient-specific drug screening for HCC. We recently established a novel modeling system using three-dimensional (3D) bioprinting technology and constructed hepatorganoids with HepaRG cells, which retain the liver function and prolong the survival of mice with liver failure after abdominal transplantation. Here we extend this modeling system to establish individualized model for hepatocellular carcinoma. HCC specimens were obtained from six patients after surgery. Primary HCC cells were isolated and mixed with gelatin and sodium alginate to form the bioink for printing. Patient-derived three-dimensional bio-printed HCC (3DP-HCC) models were successfully established afterward and grew well during long-term culture. These models retained the features of parental HCCs, including stable expression of the biomarker, stable maintenances of the genetic alterations and expression profiles. 3DP-HCC models are capable of displaying the results of drug screening intuitively and quantitatively. In conclusion, 3DP-HCC models are faithful in vitro models that are reliable in long-term culture and able to predict patient-specific drugs for personalized treatment.

4.
Nat Commun ; 11(1): 5384, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097706

RESUMO

Synergistic photoredox and copper catalysis confers new synthetic possibilities in the pharmaceutical field, but is seriously affected by the consumptive fluorescence quenching of Cu(II). By decorating bulky auxiliaries into a photoreductive triphenylamine-based ligand to twist the conjugation between the triphenylamine-based ligand and the polar Cu(II)-carboxylate node in the coordination polymer, we report a heterogeneous approach to directly confront this inherent problem. The twisted and polar Cu(II)-dye conjunction endows the coordination polymer with diode-like photoelectronic behaviours, which hampers the inter- and intramolecular photoinduced electron transfer from the triphenylamine-moiety to the Cu(II) site and permits reversed-directional ground-state electronic conductivity, rectifying the productive loop circuit for synergising photoredox and copper catalysis in pharmaceutically valuable decarboxylative C(sp3)-heteroatom couplings. The well-retained Cu(II) sites during photoirradiation exhibit unique inner-spheric modulation effects, which endow the couplings with adaptability to different types of nucleophiles and radical precursors under concise reaction conditions, and distinguish the multi-olefinic moieties of biointeresting steride derivatives in their late-stage trifluoromethylation-chloration difunctionalisation.

5.
Fitoterapia ; 147: 104755, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33069835

RESUMO

Hypersubones D-H (1-5), five new polycyclic polyprenylated acylphloroglucinols (PPAPs) type metabolites with intriguing adamantane and homo-adamantane skeletons, were characterized from aerial parts of Hypericum subsessile. Compounds 1-2 were elucidated to share an adamantane core with 28,29-expoxide moiety, while 3-5 were homo-adamantane type PPAPs sharing a1,2-dioxepane ring system. Their structures were determined on the basis of comprehensive NMR and MS spectroscopic data.The anti-adipogenesis activities of these isolates were evaluated through employing 3T3-L1 cells as an in vitro system using oil red O staining, and compounds 1, 2 and 5 were able to significant inhibit the adipocyte differentiation, which implied that these compounds possessed anti-adipogenic activity.

6.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(10): 1238-1242, 2020 Oct 15.
Artigo em Chinês | MEDLINE | ID: mdl-33063486

RESUMO

Objective: To investigate the effectiveness of arthroscopic all-inside combined with outside-in "suture loop" repair for meniscus bucket-handle tear (BHT). Methods: Between August 2016 and May 2019, 44 case of meniscus BHT were treated with arthroscopic all-inside combined outside-in "suture loop". There were 29 males and 15 females with an average age of 26.6 years (range, 18-42 years). The causes of injury included sports injury in 31 cases, falling injury in 7 cases, and sprain in 6 cases. There were 32 cases of medial meniscus posterior horn tears and 12 cases of lateral meniscus posterior horn tears. The disease duration ranged from 6 weeks to 3 months. Thirty-three cases were complicated with anterior cruciate ligament rupture. All patients had normal lower limb alignment. The preoperative Lysholm score was 42.1±9.1. According to the evaluation criteria of MRI and Barrett et al., the healing of meniscus was evaluated, and the effectiveness was evaluated by Lysholm score. Results: All the 44 patients were followed up 8-36 months with an average of 16.8 months. At last follow-up, according to the evaluation criteria of Barrett et al., 39 cases were clinically healed, 5 cases were not healed, the clinical healing rate was 88.6%; according to MRI evaluation, 32 cases were completely healed, 7 cases were partially healed, and 5 cases were not healed, the total healing rate was 88.6%, and the complete healing rate was 72.7%. Lysholm score was 87.8±4.8, which was significantly different from that before operation ( t=31.060, P=0.000). Conclusion: Arthroscopic all-inside combined with outside-in "suture loop" repair is a reliable and effective method for the meniscus BHT, which can obtain good joint function.


Assuntos
Traumatismos do Joelho , Lesões do Menisco Tibial , Adolescente , Adulto , Artroscopia , Feminino , Humanos , Masculino , Suturas , Lesões do Menisco Tibial/cirurgia , Resultado do Tratamento , Adulto Jovem
7.
Cell Mol Biol (Noisy-le-grand) ; 66(5): 185-190, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33040834

RESUMO

The radiation sensitivity of tumor cells is closely related to tumor cell hypoxia. Hypoxia-inducible factor-1α (HIF-1α) is considered a key transcription factor which regulates the sensitivity of hypoxic tumor cells to radiotherapy. On the other hand, some studies have shown that gold nanomaterials improve radiation sensitivity. However, studies on the effect of gold nanomaterials carrying HIF-1αsiRNA on tumor radiotherapy, and the underlying mechanisms are limited. Thus, the present study was aimed at investigating the effect of gold nanocomposites (AuNRs) carrying HIF-1αsiRNA (AuNRs-HIF-1αsiRNA) on the radiation sensitivity of nasopharyngeal carcinoma (NPC) hypoxia cells. The effect of AuNRs-HIF-1αsiRNA on radiation sensitivity of hypoxic NPC cells was determined under X-ray irradiation. The results showed that Au-HIF-1αsiRNA improved the radio-sensitivity of NPC tumor. Thus, this study has demonstrated that gold nanomaterials carrying HIF-1αsiRNA effectively increased the radio-sensitivity of hypoxic tumor, thereby improving the effect of radiotherapy on NPC cells.

8.
Clin Spine Surg ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33074945

RESUMO

STUDY DESIGN: This was a retrospective cohort review. OBJECTIVE: The objective of this study was to analyze depression using Beck Depression Inventory (BDI) and Hamilton Depression Scale (HAMD-24), and to correlate with clinical outcomes and improvement in adults with following lumbar fusion. SUMMARY OF BACKGROUND DATA: Psychological factors such as depression are found to influence outcomes and improvement following spinal surgery. It is still unclear whether there are differences during screening for depression by different implementations to predict outcomes for spine surgery. MATERIALS AND METHODS: Between July 2016 and May 2018, patients with degenerative lumbar disease, who underwent lumbar fusion were enrolled in this study. The patient's characteristics, preoperative BDI and HAMD-24 score, and preoperative and postoperative outcomes were collected, respectively. Depressed patients were identified by a score of BDI≥15 or HAMD-24>20, respectively. Preoperative and postoperative outcome scores, absolute changes, and recovery ratios of disability and pain were compared within and between groups. Finally, univariate and multiple linear regression analyses was performed to reveal the relationship between preoperative depressive states and outcomes and improvement. RESULTS: A total of 125 patients were eligible in the study, with 113 (90.4%) patients without depressive symptoms and 12 (9.6%) depressed patients by BDI, and 97 (77.6%) patients without depressive symptoms and 28 (22.4%) depressed patients by HAMD-24. Both higher BDI and HAMD-24 group was found to have significant worse preoperative and postoperative outcomes as well as less recovery ratios than the patients without depressive symptoms. Univariate and multiple linear regression analyses suggested that preoperative depression might be a potential predictor of worse surgical outcomes. CONCLUSIONS: Depressive symptoms might lead to smaller magnitude of improvement. Moreover, both preoperative BDI and HAMD-24 score was a negative predictor of postoperative outcomes and can be regarded as a candidate to screen for depression preoperatively.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32996683

RESUMO

Arranging ionic liquids (ILs) with long-range order can not only enhance their performances in a desired application, but can also help elucidate the vital relationship between structure and properties. However, achieving long-range ordered ILs is still a formidable challenge and no successful example has been reported to date. In this work, we report a feasible strategy to achieve a crystalline IL via coordination self-assembly based reticular chemistry. The first crystalline IL bearing a long-range ordered framework, IL 1 MOF , was prepared by designing an IL bridging ligand and then connecting them with metal clusters. IL 1 MOF possesses a very unique structure, where the IL ligands are arranged on a long-range ordered framework but have a labile ionic center. This structure enables IL 1 MOF to break through the typical limitation where the solid ILs have lower proton conductivity than their counterpart bulk ILs. IL 1 MOF shows 2-4 orders of magnitude higher proton conductivity than its counterpart IL monomer across a wide temperature range. Its conductivity is also an order magnitude higher than the highest reported values for solid protic IL derivatives and MOF-based anhydrous proton conductors at room temperature. Moreover, by confining the IL within ultramicropores (< 1 nm), IL 1 MOF suppresses the liquid-solid phase transition temperatures to lower than -150 o C, allowing it to function with high conductivity in a subzero temperature range. This work is expected to open a toolbox for designing new-generation IL materials for important applications.

10.
Clin Chem ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894753

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody testing is an important tool in assessment of pandemic progress, contact tracing, and identification of recovered coronavirus disease 2019 (COVID-19) patients. We evaluated an orthogonal testing algorithm (OTA) to improve test specificity in these use cases. METHODS: A two-step OTA was applied where individuals who initially tested positive were tested with a second test. The first-line test, detecting IgG antibodies to the viral nucleocapsid protein was validated in 130 samples and the second-line test, detecting IgG antibodies to the viral spike protein in 148 samples. The OTA was evaluated in 4,333 clinical patient specimens. The seropositivity rates relative to the SARS-CoV-2 PCR positivity rates were evaluated from our entire patient population data (n = 5,102). RESULTS: The first-line test resulted in a clinical sensitivity of 96.4% (95% CI; 82.3% to 99.4%), and specificity of 99.0% (95% CI; 94.7% to 99.8%), whereas the second-line test had a sensitivity of 100% (95% CI; 87.7% to 100%) and specificity of 98.4% (95% CI; 94.2% to 99.5%). Using the OTA, 78/98 (80%) of initially positive SARS-CoV-2 IgG results were confirmed with a second-line test, while 11/42 (26%) of previously diagnosed COVID-19 patients had no detectable antibodies as long as 94 days post PCR diagnosis. CONCLUSION: Our results show that an OTA can be used to identify patients who require further follow-up due to potential SARS CoV-2 IgG false positive results. In addition, serological testing may not be sufficiently sensitive to reliably detect prior COVID-19 infection.

11.
Chemistry ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32986277

RESUMO

Subtle ligand modifications on Ru(II)-polypyridyl complexes may result in different excited-state characteristics, which provides the opportunity to tune their photo-physicochemical properties and subsequently change their biological functions. Here, a DNA targeting Ru(II)-polypyridyl complex (named Ru1 ) with highly photosensitizing 3 IL (intraligand) excited state was designed based on a classical DNA-intercalator [Ru(bpy) 2 (dppz)]·2PF 6 by incorporation of dppz ligand tethered with pyrenyl group, which has 4 orders of magnitude higher potency than the model complex [Ru(bpy) 2 (dppz)]·2PF 6 upon light irradiation. This study provides a facile strategy for the design of organelle-targeting Ru(II)-polypyridyl complex with dramatically improved photobiological activity.

12.
Environ Toxicol ; 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32951314

RESUMO

Radiotherapy is a common therapy method for nasopharyngeal carcinoma (NPC) treatment; however, radioresistance greatly limits the clinical efficiency and prognosis of NPC patients. Therefore, it is extremely urgent to reveal the underlying mechanism contributing to radioresistance and find possible diagnostic biomarkers. Here, we collected the spheroids formed by NPC cells, which had been confirmed to hold the stem cell-like traits, and found that these spheroids exhibited a certain degree of radioresistance. Additionally, NPC spheroids displayed a certain degree of ferroptosis resistance, as evident by the decrease of iron concentration in lysosomes and lipid peroxides oxygen, and increase of glutathione (GSH) level. Furthermore, we revealed that itraconazole triggered the ferroptosis of NPC spheroids, which is characterized as the increase of iron concentration and lipid peroxides oxygen, and decrease of GSH level, and decreased the cell viability of NPC spheroids. Notably, itraconazole partially reversed the radioresistance of NPC spheroids. Mechanistically, we found that itraconazole can sequester iron in lysosome and thus trigger ferroptosis; this is essential for itraconazole-mediated attenuation on NPC spheroid stemness. Therefore, this study provides evidences showing that itraconazole might be used for killing NPC stem cells and thus attenuate radioresistance.

14.
Zhongguo Zhong Yao Za Zhi ; 45(15): 3603-3607, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893549

RESUMO

Osteoporosis fracture with high disability and mortality is a difficult problem that seriously affects the life quality of individuals. At present, there is still a lack of anti-osteoporosis drugs with clear target and significant efficacy in the clinical practice. Rehmanniae Radix and its prescriptions have significant clinical effects. In this regard, more and more studies have reported the effects and mechanisms of Rehmanniae Radix and its active components, and the certain research outputs have been achieved. In this article, the PubMed, Web of science, China National Knowledge Infrastructure, and Wanfang database were searched to collect and organize the latest research progress of Rehmanniae Radix treatment of osteoporosis in the recent 10 years. We summarized the research dynamics as well as the function indexes and mechanisms of the raw and processed Rehmanniae Radix, active ingredients such as catalpol, aucubin, acteoside and Rehmanniae Radix polysaccharide, and their formulating prescriptions, and then excavated the potential active ingredients, targets and signaling pathways, including the effect on bone marrow mesenchymal stem cells, promoting the osteoblast proliferation and promoting osteogenesis differentiation(increasing alkaline phosphatase, typeⅠ collagen, osteoprotegerin, and osteocalcin and promoting calcium deposits), increasing the bone density, inhibiting the osteoclast quantity and differentiation, promoting the osteoclast apoptosis, and reducing tartrate resistant acid phosphatase and bone resorption pit area to provide the reference and develop new ideas for developing Rehmanniae Radix prescriptions for treatment of osteoporosis and exploring its mechanism.


Assuntos
Medicamentos de Ervas Chinesas , Osteoporose , Rehmannia , China , Humanos , Osteogênese
15.
BMC Cancer ; 20(1): 870, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907530

RESUMO

BACKGROUND: BRAF-activated noncoding RNA (BANCR) is aberrantly expressed in various tumor tissues and has been confirmed to function as a tumor suppressor or oncogene in many types of cancers. Considering the conflicting results and insufficient sampling, a meta-analysis was performed to explore the prognostic value of BANCR in various carcinomas. METHODS: A comprehensive literature search of PubMed, Web of Science, EMBASE, Cochrane Library and the China National Knowledge Infrastructure (CNKI) was conducted to collect relevant articles. RESULTS: The pooled results showed a strong relationship between high BANCR expression and poor overall survival (OS) (HR (hazard ratio) =1.60, 95% confidence interval (CI): 1.19-2.15, P = 0.002) and recurrence-free survival (RFS) (HR = 1.53, 95% CI: 1.27-1.85, P < 0.00001). In addition, high BANCR expression predicted advanced tumor stage (OR (odds ratio) =2.39, 95% CI: 1.26-4.53, P = 0.008), presence of lymph node metastasis (OR = 2.03, 95% CI: 1.08-3.83, P = 0.03), positive distant metastasis (OR = 3.08, 95% CI: 1.92-4.96, P < 0.00001) and larger tumor sizes (OR = 1.63, 95% CI: 1.09-2.46, P = 0.02). However, no associations were found for smoking status (OR = 1.01, 95% CI: 0.65-1.56, P = 0.98), age (OR = 0.88, 95% CI: 0.71-1.09, P = 0.236) and sex (OR = 0.91, 95% CI: 0.72-1.16, P = 0.469). The sensitivity analysis of OS showed that the results of each publication were almost consistent with the combined results, and the merged results have high robustness and reliability. CONCLUSIONS: The results showed that elevated BANCR expression was associated with unfavorable prognosis for most cancer patients, and BANCR could serve as a promising therapeutic target and independent prognostic predictor in most of cancer types.

17.
J Interv Cardiol ; 2020: 4982987, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32863790

RESUMO

Background: Urinary kidney injury molecule 1 (uKIM-1) is a proximal tubular injury biomarker for predicting acute kidney injury (AKI); its prognostic value varies depending on the clinical and population characteristics. However, the predictive value of uKIM-1 for diagnosis of contrast-induced acute kidney injury (CI-AKI) remains unclear. Method: Medline, Embase, ClinicalTrials.gov, Cochrane Library database, and the China National Knowledge Infrastructure (CNKI) were used to identify relevant studies from their inception to November 31, 2019. Studies that met the inclusion criteria were included. Relevant data were extracted to obtain pooled sensitivity (SEN) and specificity (SPE), summary receiver operating characteristic curve (ROC), and area under the ROC (AUC or AUROC). A bivariate mixed-effects regression model was used for data analysis. Results: A total of 946 patients from 8 eligible studies were included. Across all the studies, the diagnostic odds ratio (DOR) for uKIM-1 level to predict CI-AKI was 19 (95% CI 10-39), with SEN and SPE of 0.84 and 0.78, respectively. The AUROC for uKIM-1 in predicting CI-AKI was 0.88 (95% CI 0.85-0.90). There was a substantial heterogeneity across the studies (I 2 was 37.73% for the summary sensitivity and 69.31% for the summary specificity). Conclusion: Urinary KIM-1 has a high predictive value for diagnosis of CI-AKI in patients who have undergone cardiac catheterization.

18.
BMJ Open ; 10(9): e036423, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912980

RESUMO

OBJECTIVES: The microscopic evaluation of slides has been gradually moving towards all digital in recent years, leading to the possibility for computer-aided diagnosis. It is worthwhile to know the similarities between deep learning models and pathologists before we put them into practical scenarios. The simple criteria of colorectal adenoma diagnosis make it to be a perfect testbed for this study. DESIGN: The deep learning model was trained by 177 accurately labelled training slides (156 with adenoma). The detailed labelling was performed on a self-developed annotation system based on iPad. We built the model based on DeepLab v2 with ResNet-34. The model performance was tested on 194 test slides and compared with five pathologists. Furthermore, the generalisation ability of the learning model was tested by extra 168 slides (111 with adenoma) collected from two other hospitals. RESULTS: The deep learning model achieved an area under the curve of 0.92 and obtained a slide-level accuracy of over 90% on slides from two other hospitals. The performance was on par with the performance of experienced pathologists, exceeding the average pathologist. By investigating the feature maps and cases misdiagnosed by the model, we found the concordance of thinking process in diagnosis between the deep learning model and pathologists. CONCLUSIONS: The deep learning model for colorectal adenoma diagnosis is quite similar to pathologists. It is on-par with pathologists' performance, makes similar mistakes and learns rational reasoning logics. Meanwhile, it obtains high accuracy on slides collected from different hospitals with significant staining configuration variations.

19.
J Am Soc Nephrol ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912934

RESUMO

BACKGROUND: Eighteen known susceptibility loci for IgAN account for only a small proportion of IgAN risk. METHODS: Genome-wide meta-analysis was performed in 2628 patients and 11,563 controls of Chinese ancestry, and a replication analysis was conducted in 6879 patients and 9019 controls of Chinese descent and 1039 patients and 1289 controls of European ancestry. The data were used to assess the association of susceptibility loci with clinical phenotypes for IgAN, and to investigate genetic heterogeneity of IgAN susceptibility between the two populations. Imputation-based analysis of the MHC/HLA region extended the scrutiny. RESULTS: Identification of three novel loci (rs6427389 on 1q23.1 [P=8.18×10-9, OR=1.132], rs6942325 on 6p25.3 [P=1.62×10-11, OR=1.165], and rs2240335 on 1p36.13 [P=5.10×10-9, OR=1.114]), implicates FCRL3, DUSP22.IRF4, and PADI4 as susceptibility genes for IgAN. Rs2240335 is associated with the expression level of PADI4, and rs6427389 is in high linkage disequilibrium with rs11264799, which showed a strong expression quantitative trail loci effect on FCRL3. Of the 24 confirmed risk SNPs, six showed significant heterogeneity of genetic effects and DEFA showed clear evidence of allelic heterogeneity between the populations. Imputation-based analysis of the MHC region revealed significant associations at three HLA polymorphisms (HLA allele DPB1*02, AA_DRB1_140_32657458_T, and AA_DQA1_34_32717152) and two SNPs (rs9275464 and rs2295119). CONCLUSIONS: A meta-analysis of GWAS data revealed three novel genetic risk loci for IgAN, and three HLA polymorphisms and two SNPs within the MHC region, and demonstrated the genetic heterogeneity of seven loci out of 24 confirmed risk SNPs.  These variants may explain susceptibility differences between Chinese and European populations.

20.
Clin J Am Soc Nephrol ; 15(10): 1394-1402, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-32963018

RESUMO

BACKGROUND AND OBJECTIVES: Since December 2019, coronavirus disease 2019 (COVID-19) outbreak occurred and has rapidly spread worldwide. However, little information is available about the AKI in COVID-19. We aimed to evaluate the incidence, risk factors, and prognosis of AKI in adult patients with COVID-19. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective cohort study of 1392 patients with COVID-19 admitted to a tertiary teaching hospital. Clinical characteristics and laboratory data were extracted from electronic hospitalization and laboratory databases. AKI was defined and staged according to the 2012 Kidney Disease: Improving Global Outcomes criteria. Risk factors for AKI and the association of AKI with in-hospital mortality were assessed. RESULTS: A total of 7% (99 of 1392) of patients developed AKI during hospitalization, 40% (40 of 99) of which occurred within 1 week of admission. Factors associated with a higher risk of AKI include severe disease (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.37 to 3.67), higher baseline serum creatinine (OR, 2.19; 95% CI, 1.17 to 4.11), lymphopenia (OR, 1.99; 95% CI, 1.12 to 3.53), and elevated D-dimer level (OR, 2.68; 95% CI, 1.07 to 6.70). The in-hospital mortality in patients with AKI stage 1, stage 2, and stage 3 was 62%, 77%, and 80%, respectively. AKI was associated with in-hospital mortality even after adjustment for confounders (OR, 5.12; 95% CI, 2.70 to 9.72). CONCLUSIONS: AKI is uncommon but carries high in-hospital mortality in patients with COVID-19.


Assuntos
Lesão Renal Aguda/mortalidade , Betacoronavirus/patogenicidade , Infecções por Coronavirus/mortalidade , Mortalidade Hospitalar , Pneumonia Viral/mortalidade , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/terapia , Lesão Renal Aguda/virologia , Idoso , China , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
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