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BACKGROUND: Nivolumab+ipilimumab (NIVO+IPI) has demonstrated superior overall survival (OS) and durable response benefits versus sunitinib (SUN) with long-term follow-up in patients with advanced renal cell carcinoma (aRCC). We report updated analyses with 8 years median follow-up from CheckMate 214. PATIENTS AND METHODS: Patients with aRCC (N=1096) were randomized to NIVO 3 mg/kg plus IPI 1 mg/kg Q3W × four doses, followed by NIVO (3 mg/kg or 240 mg Q2W or 480 mg Q4W); or SUN (50 mg) once daily for 4 weeks on, 2 weeks off. Endpoints included OS, and independent radiology review committee-assessed progression-free survival (PFS) and objective response rate (ORR) in intermediate/poor-risk (I/P; primary), intent-to-treat (ITT; secondary), and favorable-risk (FAV; exploratory) patients. RESULTS: With 8 years (99.1 months) median follow-up, the HR (95% CI) for OS with NIVO+IPI versus SUN was 0.72 (0.62-0.83) in ITT patients, 0.69 (0.59-0.81) in I/P patients, and 0.82 (0.60-1.13) in FAV patients. PFS probabilities at 90 months were 22.8% versus 10.8% (ITT), 25.4% versus 8.5% (I/P), and 12.7% versus 17.0% (FAV), respectively. ORR with NIVO+IPI versus SUN was 39.5% versus 33.0% (ITT), 42.4% versus 27.5% (I/P), and 29.6% versus 51.6% (FAV). Rates of complete response were higher with NIVO+IPI versus SUN in all IMDC risk groups (ITT, 12.0% versus 3.5%; I/P, 11.8% versus 2.6%; FAV, 12.8% versus 6.5%). Median duration of response (95% CI) with NIVO+IPI versus SUN was 76.2 versus 25.1 months [59.1-not estimable (NE) versus 19.8-33.2; ITT], 82.8 versus 19.8 months [54.1-NE versus 16.4-26.4; I/P], and 61.5 versus 33.2 months [27.8-NE versus 24.8-51.4; FAV]). Incidence of treatment-related adverse events was consistent with previous reports. Exploratory post hoc analyses are reported for FAV patients, those receiving subsequent therapy based on their response status, clinical subpopulations, and adverse events over time. CONCLUSIONS: Superior survival, durable response benefits, and a manageable safety profile were maintained with NIVO+IPI versus SUN at 8 years, the longest phase III follow-up for a first-line checkpoint inhibitor combination therapy in aRCC.
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Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of adrenal cortical carcinoma (ACC) in children. Methods: Twenty-five children with ACC diagnosed in the Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from March 2014 to August 2022 were retrospectively analyzed. The related literature was reviewed. Results: A total of 25 children with ACC were collected, including 11 males and 14 females, with a male to female ratio of 1.0â¶1.3. The patient ages ranged from 8 months to 14 years (median, 4 years). Eighteen cases with clinical data had functional tumors (18/22, 81.8%) presenting with virilization or precocious puberty (15/18), symptoms related to hypercortisolism (8/18) or endocrine symptoms mixed with both (5/18), while 3 cases (3/22, 13.6%) had unknown clinical data. The clinical manifestations of four patients with nonfunctional tumors were an abdominal mass and/or abdominal pain, walking instability and others. Grossly, the average maximum diameter of the tumor was 9.4 cm. Most of the tumors were nodular and partially encapsuled. The cut surfaces were gray or gray brown, soft with hemorrhage. Histologically, the tumor cells were diffusely distributed, separated by a vascular-rich network. The tumor cells were large, with distinct nucleoli, abundant eosinophilic or clear cytoplasm, and round or oval nuclei. The mitotic index was high, and atypical mitoses were common. Necrosis, calcification, capsule invasion or/and venous invasion were present. In some cases, the tumor invaded the surrounding soft tissues or kidneys. Immunohistochemically, the tumor cells were diffusely positive for syn and SF1 and focally positive for α-inhibin, Melan A and Calretinin, but negative for CgA. Ki-67 proliferation index ranged from 2%-90%. TP53 gene status was examined in 7 cases, in which mutations were detected in 4 cases. Follow-up data was obtained in 21 patients, among whom 18 received chemotherapy and 3 received radiotherapy. Distant metastasis occurred in 13 patients. Median progression-free survival (PFS) was 11.2 months and median overall survival (OS) was 54.7 months. Patients aged less than 5 years had a better prognosis for OS (P<0.05) than the older ones (≥5 years), but a similar PFS (P>0.05). Male patients and Ki-67 proliferation index <15% had a better prognosis tendency for OS, but there was no statistically significant difference (P>0.05). Conclusions: ACC in children is a rare, often functional tumor associated with Li-Fraumeni genetic syndrome and has a poor prognosis. Diagnosis and differential diagnosis require a combination of morphological, phenotypic and clinical analysis.
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Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Criança , Humanos , Masculino , Feminino , Lactente , Estudos Retrospectivos , Antígeno Ki-67 , ChinaRESUMO
Pancreatic cancer patients often have complaints such as upper abdominal pain and obstructive jaundice when seeking diagnosis and treatment. However, acute pancreatitis as a rare initial clinical manifestation of pancreatic cancer is often overlooked in clinical practice. This oversight often leads to a delayed diagnosis of pancreatic cancer, uncertainty in treatment strategies, and significantly affects patients' quality of life and prognosis. Therefore, early diagnosis and treatment, and active follow-up are crucial for patients with acute pancreatitis as an initial symptom of pancreatic cancer. Upon admission to such patients, common causes such as gallstones, alcohol abuse, and hyperlipidemia should be initially ruled out. Evaluation with tumor markers, CT and MRI, and endoscopic ultrasound are essential to confirm the diagnosis of pancreatic cancer. For patients with mild pancreatitis, managing peripancreatic inflammation first before radical resection of pancreatic cancer could reduce postoperative complications. Moreover, pancreatitis serves as a high-risk factor for pancreatic cancer, so it is crucial to closely follow up patients with pancreatitis to detect pancreatic cancer early.
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BACKGROUND: To study the efficacy and nephrotoxicity of polymyxin B in the treatment of elderly patients with carbapenem-resistant organism (CRO) infection. METHODS: The clinical and microbiological data of patients with CRO-infected sepsis treated with polymyxin B were retrospectively analyzed. The effective rate, bacterial clearance, incidence and recovery rate of acute renal injury (AKI) and prognosis-related indicators in AKI at different stages were compared. RESULTS: The effective rate of 215 elderly patients with CRO infection treated with polymyxin was 50.7%. The total bacterial clearance rate was 44.2%, the total incidence of AKI was 37.2%, the recovery rate of AKI was 35%, and the incidence range of polymyxin B-related AKI was 10.2-37.2%. Logistic multivariate regression analysis showed that the predictors of AKI in elderly patients were high APACHE II score, long duration of polymyxin, chronic renal insufficiency and ineffective outcome; the ROC curve showed that the cutoff value for predicting AKI was a serum creatinine concentration of 73 mmol/L before polymyxin B use, and the AUC was 0.931. CONCLUSIONS: Rational use of polymyxin B is safe and effective in elderly patients with CRO infection, and its effective outcome can improve the recovery rate of AKI.
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Injúria Renal Aguda , Infecções Bacterianas , Humanos , Idoso , Polimixina B/efeitos adversos , Antibacterianos/efeitos adversos , Estudos Retrospectivos , Infecções Bacterianas/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Carbapenêmicos/efeitos adversosRESUMO
Agriculture produces food, fiber and biofuels for the world's growing population, however, agriculture can be a major contributor of nitrogen (N) losses including emissions of ammonia (NH3), nitrous oxide (N2O) and nitrate (NO3-) leaching and runoff. A Canadian Agricultural Nitrogen Budget for Reactive N (CANBNr) model was developed to estimate the soil N balance in 3487 soil landscape of Canada polygons from 1981 to 2016. The CANBNr model integrates NH3 emission from fertilizers, manure from housing, storage and field, as well as direct/indirect N2O emissions from fertilizers, manures, crop residues and soil organic matter. The NO3- leaching is estimated based on the residual soil N (RSN) at harvest and drainage derived with the DeNitrification-DeComposition (DNDC) model. From 1981 to 2016, the N input from fertilizer and N fixation increased at a greater rate than N removal in harvested crops in all provinces of Canada, resulting in an increase in the RSN and N losses. In 2016, the Prairie provinces had lower N losses (11.7 kg N ha-1) from N2O, NH3 and NO3- compared with 43.2 kg N ha-1 in central Canada, and 76.5 kg N ha-1 in Atlantic Canada. However, the Prairie provinces had 84.3% of the total Canadian farmland (74.3% of the total Canadian N input), while central Canada had 12.9% of Canadian farmland (21.7% of the total Canadian N input). In the Prairie provinces, the total N2O loss from fertilizer N ranged 4.4-8.6 Gg N whereas NH3 loss ranged from 17.1 to 44.6 Gg N and these values were influenced by both emission intensity and total land area. Total N2O losses from manure were highest in Alberta, Ontario and Quebec resulting in 4.8, 4.4, and 3.4 Gg N and NH3 losses from manure were also highest in these 3 provinces at 61.1, 45.2 and 40.4 Gg N, respectively. Nitrate leaching was impacted by drainage volumes, soil type and N inputs. In the non-growing season, NO3- leaching losses (36-yr average) were 63.3 Gg in Ontario and 57.5 Gg N in Quebec compared with 20.8 Gg N for Ontario and 35.5 Gg N for Quebec in the growing season. In contrast, the Prairie provinces showed higher NO3- leaching in the growing season (23.1-37.4 Gg N) than in the non-growing season (10.4-13.7 Gg N). In summary, total fertilizer N increased the most over the 36 years in the Prairies which resulted in increased RSN and N leaching losses that will require further intervention.
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Fertilizantes , Solo , Solo/química , Nitratos , Esterco , Agricultura , Nitrogênio/análise , Ontário , Produtos Agrícolas , Óxido Nitroso/análiseRESUMO
BACKGROUND: Vitrification of embryos has become the basic means of assisted reproductive technology (ART) therapy in recent years. Concerns have also been raised about the safety of vitrification and the effect of cryopreservation time. Most of the previous studies were on the data within 6 years of cryopreservation. OBJECTIVE: In this study, we aimed to evaluate the impact of long-term cryopreservation (>6 years) on pregnancy and neonatal outcomes. MATERIALS AND METHODS: This research was a single-center, retrospective analysis, including 426 frozen-thawed embryo transfer (FET) cycles. Patients who participated in IVF-FET cycles between January 2013 to December 2020 were analyzed. Preferentially matched participants were divided into three groups according to storage time: group A (>72 months), group B (0-3 months, propensity score matching [PSM] according to the age of oocyte retrieval), and group C (0-3 months, PSM according to the age of embryo transfer). RESULTS: Our results revealed that there were no significant differences in human chorionic gonadotropin [HCG] positive rate, clinical pregnancy rate, miscarriage rate, live birth rate, and neonatal outcomes when the embryo storage duration >72 months. But the proportion of high birth weight was higher in group A (>72 months) when matched according to age at embryo transfer. CONCLUSION: The results of our study showed that long-term cryopreservation had no effect on the pregnancy and neonatal outcomes of vitrification. The results offer evidence for the safety of using long-term cryopreservation embryos after vitrification. DOI: 10.54680/fr23310110612.
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Criopreservação , Vitrificação , Gravidez , Recém-Nascido , Feminino , Humanos , Criopreservação/métodos , Estudos Retrospectivos , Taxa de Gravidez , Coeficiente de NatalidadeRESUMO
1. This study explored the tissue metabolic status and the relationship with inflammation in valgus-valgus deformity (VVD) broilers with increasing age.2. Tissue and blood from VVD and healthy broilers were collected at two, four and five weeks old. A fully automated biochemical analyser, real-time PCR, HE staining and enzyme-linked immunosorbent assay were used to detect tissue metabolic indexes, mRNA levels of inflammation and apoptosis cytokines in immune organs, histological changes and serum inflammation and immune-related protein contents in VVD broilers.3. The results showed that VVD increased the levels of total protein, albumin, alanine aminotransferase at five weeks of age, aspartate aminotransferase, urea and creatine kinase in blood at two weeks of age. It upregulated the gene expression of inflammatory factors IL-1ß, IL-6, IL-8, TNF-α, NF-κB and TGF-ß and apoptotic factors FAS, Bcl-2, caspase-3 and 9 in immune organs; increased levels of serum proteins TNF-α, IL-1ß and IL-6 and decreased levels of serum immunoglobulins IgY and CD3+.4. In addition, with increasing age, IL-10 gene expression gradually increased in the BF and decreased in the spleen.5. In conclusion, VVD broilers have disorders of liver and kidney metabolism, inflammation and apoptosis of immune organs and increased levels of serum inflammatory factor proteins.
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Galinhas , Fator de Necrose Tumoral alfa , Animais , Fator de Necrose Tumoral alfa/metabolismo , Galinhas/genética , Galinhas/metabolismo , Interleucina-6 , Apoptose , Inflamação/veterináriaRESUMO
1. Valgus-varus deformity (VVD) is a common leg bone problem in broilers that causes serious economic losses to the breeding industry. The genetic aetiology of VVD is not clear, which restricts the genetic control of VVD.2. In this study, knee cartilage of 35-day-old VVD and normal broilers was sequenced by whole-genome bisulphite sequencing (WGBS). The unique whole-genome DNA methylation profile of VVD broilers was described, and the methylation data and transcription data were used for joint analysis.3. The mean methylation level of the VVD group was greater than that in the normal group. A total of 4315 differentially methylated regions (DMRs) were detected from methylation data, with the highest DMR density on chromosomes 25, 27, 31 and 33. DMRs were mainly located in introns, which accounted for more than 60%, followed by promoter and exon regions.4. A total of 2326 differentially methylated genes (DMGs) were identified from DMRs, including 1159 genes with upregulated DMRs, 936 genes with downregulated DMRs, and 231 genes with two types of DMRs.5. The ESPL1 gene may be an important epigenetic gene of VVD. The methylation of particular CpG17, CpG18 and CpG19 sites in the promoter region of the ESPL1 gene may hinder the binding of transcription factors and promoters and increase the expression of ESPL1.
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Galinhas , Metilação de DNA , Animais , Galinhas/genética , Perfilação da Expressão Gênica/veterinária , Regulação da Expressão Gênica , DNA , Epigênese GenéticaRESUMO
Objective: To analyze the ultrasonic manifestations, clinical features, high risk factors and key points of pregnancy management in prenatal diagnosis of umbilical artery thrombosis (UAT). Methods: The data of 31 pregnant women of UAT diagnosed by prenatal ultrasonography and confirmed after birth from July 2017 to July 2022 at the Women's Hospital, Zhejiang University School of Medicine were retrospectively analyzed, including the maternal characteristics, pregnancy outcomes and fetal complications. In addition, the baseline data and pregnancy outcomes were compared in 21 patients who continued pregnancy after diagnosis of UAT. Of the 21 UAT cases that continued pregnancy, 10 cases were treated with low molecular weight heparin (LMWH; LMWH treatment group), while the other 11 patients had expectant treatment(expectant treatment group). Results: The age of the 31 pregnant women was (30.2±4.7) years, of which 5 cases (16%,5/31) were advanced age pregnant women. The gestational age at diagnosis was (32.9±4.0) weeks, and the gestational age at termination of pregnancy was (35.6±2.9) weeks. In 31 fetuses with UAT, 15 cases (48%) had fetal distress, 11 cases (35%) had fetal growth restriction, and 3 cases (10%) had intrauterine stillbirth. There were 28 cases of live births, including 26 cases by cesarean section and 2 cases by vaginal delivery. There were also 3 stillbirths, all delivered vaginally. Four neonates had mild asphyxia and two newborns had severe asphyxia. Among the 31 cases, 10 cases were terminated immediately after diagnosis, the gestational age at diagnosis was (35.9±2.9) weeks. Another 21 pregnancies continued, and their gestational age at diagnosis was (31.4±3.7) weeks. The median prolonged gestational age in LMWH treatment group was 7.9 weeks (4.6-9.4 weeks), and all were live births. The median prolonged gestational age in the expectant treatment group was 0.6 weeks (0.0-1.0 weeks), and 2 cases were stillbirths. There was a statistically significant difference in prolonged gestational age (P=0.002). Conclusions: Ultrasound is the preferred method for prenatal detection of UAT. Clinicians need to be vigilant for UAT when a newly identified single umbilical artery is detected by ultrasound in the second or third trimesters. The decision to continue or terminate the pregnancy depends on the gestational age and the condition of fetus. Attention should be paid to fetal movements as the pregnancy continues. The treatment of LMWH as soon as possible after diagnosis of UAT may improve the pregnancy outcome.
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Cesárea , Natimorto , Gravidez , Recém-Nascido , Feminino , Humanos , Adulto , Lactente , Artérias Umbilicais/diagnóstico por imagem , Asfixia , Estudos Retrospectivos , Heparina de Baixo Peso Molecular/uso terapêutico , Resultado da Gravidez , Retardo do Crescimento Fetal/terapia , Ultrassonografia Pré-Natal/métodos , Idade GestacionalRESUMO
BACKGROUND: Artificial Intelligence (A.I) and deep learning-based algorithms are increasingly being used in dermatology following the emergence of powerful smartphones with high-resolution cameras. OBJECTIVES: To use an A.I-based algorithm, validated by dermatologists, to compare the evolution of the skin ageing process among Chinese and European women. METHODS: Selfie images were taken by 465 587 European and 79 016 Chinese women ranging from 18 to 85 and 18 to 69 years old, respectively, without facial skin diseases and who had access to a smartphone with a high-resolution camera (≥4 Megapixels). The selfies were analysed by facial skin diagnostic using a smartphone application to grade the severity of 9 facial signs (including wrinkles, sagging, vascular, pigmentation signs, pores). RESULTS: Wrinkles/texture, ptosis and sagging increased linearly with age in European women compared to lower scores and more gradual increase in the younger age-classes in Chinese women. In Chinese women, pigmentation signs increased regularly between 18 and 40 years, plateaued between 40 and 60 years, then increased in the over 60s compared to lower scores and a slower more regular increase with age in European women. Vascularization signs increased steadily with age in European women compared to no significant change in Chinese women. CONCLUSIONS: Marked differences were observed in the skin ageing process between European and Chinese populations, both in the prevalence of each facial ageing sign and their kinetics. Automatic grading performed on selfies and analysed by A.I is a fast and confidential method for quantifying signs of facial ageing and identifying the main issues for each population and age-class, which is of practical interest, as it will allow the development of tailored prevention and therapeutic measures.
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Transtornos da Pigmentação , Envelhecimento da Pele , Idoso , Inteligência Artificial , Povo Asiático , China , Face , Feminino , HumanosRESUMO
1. Chicken muscle is an important factor in meat quality and its development is controlled by a complex regulatory network.2. The following study examined the expression of miR-30a-3p in Gushi chicken breast muscle tissue and found that it was differentially expressed at different embryonic stages, reaching a peak in the 14-day-old embryo (E14).3. The effect of miR-30a-3p on chicken primary myoblasts (CPMs) was explored. Results from both cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) showed that this can inhibit the proliferation of myoblasts, and through cell cycle experiments, the inhibition of myoblast proliferation was found, which may be due to G0/G1 arrest in the cell cycle.4. The effect of miR-30a-3p on the differentiation of myoblasts was studied. The results showed that miR-30a-3p can promote the expression of MYOD, myogenin (MYOG), and myosin heavy chain (MYHC) genes to promote the differentiation of myoblasts. Through MYHC protein immunofluorescence experiments, it was found that miR-30a-3p can effectively increase the area of myotubes.5. Finally, mRNA transcriptome data was analysed, which showed that miR-30a-3p has 51 potential target genes. Among them, forkhead box O3 (FOXO3), ankyrin repeat domain 1 (ANKRD1), and insulin-induced 1 (INSIG1) genes were differentially expressed at different developmental stages and were enriched in Gene Ontology (GO) terms, such as cell differentiation and cellular developmental process. The data showed that tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG), BUB1 mitotic checkpoint serine/threonine kinase (BUB1), and growth arrest and DNA damage-inducible 45 (GADD45) genes were enriched in the cell cycle pathway.6. It can be speculated that miR-30a-3p plays roles through these genes in myoblast development. This research provides information for further improving knowledge of the chicken muscle development regulation network.
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Galinhas , MicroRNAs , Animais , Diferenciação Celular/genética , Proliferação de Células/genética , Galinhas/genética , Galinhas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Mioblastos/metabolismoRESUMO
Objective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t-test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P<0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.
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Cisteína , Mieloma Múltiplo , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Adulto , Idoso , Mieloma Múltiplo/diagnóstico , Reprodutibilidade dos Testes , Metaboloma , Metabolômica/métodos , Redes e Vias Metabólicas , Metionina , Serina , Fenilalanina , Treonina , BiomarcadoresRESUMO
OBJECTIVE: To investigate how to use polymyxin B rationally in order to produce the best efficacy and safety in patients with carbapenem-resistant gram-negative organisms (CRO) infection. METHODS: The clinical characteristics and microbiological results of 181 patients caused by CRO infection treated with polymyxin B in the First Affiliated Hospital from July 2018 to May 2020 were retrospectively analyzed. The bacterial clearance rate, clinical efficacy, adverse drug reactions and 28 days mortality were evaluated. RESULTS: The overall effective rate of 181 patients was 49.72%, the total bacterial clearance rate was 42.0%, and the 28 day all-cause mortality rate was 59.1%. The effective rate and bacterial clearance rate in the group of less than 24 h from the isolation of CRO to the use of polymyxin B were significantly higher than those in the group of more than 24 h. Logistics multivariate regression analysis showed that the predictive factors for effective treatment of CRO with polymyxin B were APACHEII score, duration of polymyxin B treatment, combination of polymyxin B and other antibiotics, and bacterial clearance. 17 cases (9.36%) of acute kidney injury were considered as polymyxin B nephrotoxicity and 4 cases (23.5%) recovered after polymyxin B withdrawal. After 14 days of polymyxin B use, 3 cases of polymyxin B resistance appeared, and there were 2 cases of polymyxin B resistance in the daily dose 1.5 mg/kg/day group. CONCLUSION: For CRO infection, the treatment of polymyxin B should be early, combined, optimal dose and duration of treatment, which can achieve better clinical efficacy and microbial reactions, and reduce the adverse reactions and drug resistance.
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Infecções por Bactérias Gram-Negativas , Polimixina B , Antibacterianos/efeitos adversos , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Polimixina B/efeitos adversos , Estudos RetrospectivosRESUMO
Individual identification of horses for pedigree verification and registration is important for the sustainable development of the horse industry. Horse individual identification and parentage tests commonly use the 17 short tandem repeats (STRs) recommended by the International Society for Animal Genetics (ISAG) and the locus LEX33. While many multiplex STR typing systems have been established for the horse, a sex determining marker is usually absent, and none of them can simultaneously detect all 17 ISAG recommended loci and the locus LEX33. Here, we present a 19-plex STR typing system that contains the 17 ISAG recommend loci, the locus LEX33 and amelogenin as sex determining loci. The results of our sensitivity, species specificity, stutter analysis and population data analysis, indicate that this system is a specific, sensitive, and robust tool for the identification of individuals, parentage testing and genetic research in the horse.
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Cavalos/genética , Repetições de Microssatélites , Alelos , Animais , Feminino , Frequência do Gene , Masculino , Linhagem , Reação em Cadeia da Polimerase/veterinária , Especificidade da EspécieRESUMO
Objective: To investigate the seasonal changes of benign paroxysmal positional vertigo (BPPV) onset, and explore the relationship between vascular risk factors and the seasonal patterns of BPPV. Methods: Data of 3 886 patients subjected to vestibular function examination and diagnosed with BPPV who underwent manipulation or instrumental repositioning from January 1, 2016 to December 31, 2019 in the Department of Neurology, Beijing Tiantan Hospital were retrospectively analyzed. Demographic information and medical history of the patients were recorded. Weather temperature data of Beijing were obtained and monthly averages were calculated. The relationship between the BPPV onset and temperature and seasonality was investigated. Meanwhile, the influence of vascular risk factors on the seasonal patterns of BPPV was determined. Results: BPPV is more common in women (n=2 667). The male to female ratio of patients was approximately 1â¶2, with a mean age of (55±13) years. The cases of BPPV in spring (March-May), summer (June-August), autumn (September-November) and winter (December-February) were 1 000 (25.7%), 911 (23.4%), 808 (20.8%) and 1 167 (30.0%), respectively. The peak incidence of BPPV occurred in December (n=491) and the lowest occurred in September (n=251). The number of BPPV cases diagnosed monthly was inversely correlated with mean temperature (R2=0.317; P<0.001). Patients with ≥2 vascular risk factors were at higher risk of developing BPPV in spring or winter than those without risk factors (OR=1.32, 95%CI: 1.13-1.53,P<0.001). Proportion of onset in spring or winter increased with each additional risk factor (P trend<0.001). Conclusions: BPPV often occurs in the months with low temperature (spring and winter) and the number of cases is inversely correlated with temperature. Compared with those with no vascular risk factors, patients with more vascular risk factors are more likely to develop BPPV in spring and winter.
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Vertigem Posicional Paroxística Benigna , Vestíbulo do Labirinto , Adulto , Idoso , Vertigem Posicional Paroxística Benigna/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
In this study, we analyzed 93 whole genomes from Chinese spot-billed ducks (CSB), meat-type ducks (MET), and egg and dual purpose-type ducks (EDT) to characterize the genetic material flowing between the CSB and modern ducks. Using a frequency of shared identical-by-descent method, approximately 10.9 Mb introgression segments containing 140 genes were identified showing the signatures of introgression between CSB and EDT. Meanwhile, nearly 10.6 M introgression regions containing 149 genes were identified between CSB and MET. Based on the haplotypes tree of each segment, we found that the introgression between CSB and domesticated ducks was asymmetric with a high level of gene flow from domestic to CSB and a low level of migration in the opposite direction. Moreover, we identified several genes that were introgressions from CSB and showed the signature of positive selection, which may contribute to the breeding of modern ducks. Our results provide new insight into the evolution and breeding history of domestic ducks and may be useful for the future management of wild and domestic duck populations.
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Animais Domésticos/genética , Patos/genética , Fluxo Gênico , Introgressão Genética , Animais , Cruzamento , Mapeamento Cromossômico , Evolução Molecular , Haplótipos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: These were two folds: at first, to develop an automatic grading system specifically dedicated to some facial signs of men, similar to the one previously validated on women of different ethnic ancestry and second, to assess its potential in detecting and grading the possible impacts of a severe aerial urban pollution on some facial signs of Chinese men. METHODS: In both studies, selfie images were obtained from differently aged men. Nine facial signs were automatically graded through a specific A.I-based algorithm and clinically assessed by a panel of experts and dermatologists. Selfie pictures were taken from individual smartphones of variable optical properties. The first study, designed for developing an automatic grading system, involved three comparable cohorts of men from three different regional ancestries (African, Asian, Caucasian, 110 each) the selfie images of which were acquired under four different lighting conditions. As a second use case study, the facial signs of two cohorts of Chinese men (101 and 100, each), differently aged, regularly exposed to very different aerial urban pollution conditions (UP) were analysed by the same algorithm, selfies being taken under only one lighting condition. RESULTS: -The new automatic grading system of facial signs suits well to men, showing comparable results than that the one dedicated to women and provides data in close agreement with experts' assessments. -In both cases (expert's or automatic methodology), the accuracy of the scores appeared ethnic-dependent. -The applied case confirmed previous results obtained clinically, that is, that many facial signs were found of an increased severity among men exposed to a severe urban pollution, as compared to those living in a less polluted city. -In both studies, statistical agreements between the automatic grading system and expert's assessments were reached. In some facial signs, the automatic grading system seems offering a slightly better accuracy than the assessments made by the experts. CONCLUSION: Apart from some minor limitations, this A.I-based automatic grading system, free from human intervention, performed as well as the one previously developed in women, in close agreement with expert's assessments. In epidemiological studies, this system offers an easy, fast, affordable and confidential approach in the detection and quantification of male facial signs.
OBJECTIF: Il était double: (i) de développer d'un système automatique de scorage spécifique de plusieurs signes faciaux pour les hommes, similaire à celui précédemment validé sur des femmes de différentes origines. Et (ii), de jauger ses capacités pour la détection et l'évaluation des possibles impacts d'une pollution aérienne urbaine sévère sur le visage d'hommes chinois. MÉTHODES: Dans chacune des deux études des images de type selfies d'hommes de différents âges ont été obtenues. Neuf signes faciaux ont été automatiquement évalués grâce à un algorithme spécifique basé sur l'Intelligence Artificielle (IA) puis scorés cliniquement par un panel d'experts et de dermatologues. Des selfies ont été acquis à partir de téléphones portables individuels possédants des optiques et des résolutions différentes. L'étude N°1, conçue pour développer un système de scorage automatique du visage, a regroupé trois cohortes comparables d'hommes d'origines géographiques différentes (Africain, Asiatique et Caucasien, 110 volontaires par ethnies) et a requis l'acquisition sous 4 conditions d'éclairage. L'étude N°2, comme cas pratique, a nécessité le recrutement de deux cohortes d'hommes chinois d'âges différents (101 et 101 volontaires chacune) exposés régulièrement à de très différentes conditions de pollution aérienne urbaine et pour lesquels des selfies ont été enregistrés sous une seule condition d'éclairage. RÉSULTATS: -Le nouveau système de scorage automatique de signes faciaux des hommes performe de manière satisfaisante et montre des résultats comparables à celui précédemment conçu pour les femmes et donne des mesures très proches des évaluations cliniques des experts et dermatologues. -Dans les deux cas (experts ou mesures automatiques), l'acuité des scores apparaît dépendante à l'origine ethnique. -Le cas pratique confirme nos résultats précédents obtenues cliniquement, c'est à dire que de nombreux signes faciaux ont été trouvés d'amplitude plus importante pour les hommes exposés à une pollution aérienne urbaine sévère en comparaison de ceux vivant dans une ville moins polluée. -Les deux études ont démontré l'adéquation statistique entre le système automatique et les évaluations des experts et dermatologues. Pour certains signes, une certaine supériorité de système automatique a pu être observée vis-à-vis de l'évaluation des experts. CONCLUSION: A l'exception de quelques limitations mineures, le nouveau système de scorage automatique, basé sur l'IA, du visage des hommes - ne nécessitant aucune intervention humaine - fonctionne aussi bien que celui dédié aux femmes et toujours en parfaite adéquation avec les dermatologues. Pour des études épidémiologiques, ce système offre une approche rapide, aisée, confidentielle et d'un coût très abordable pour la détection et la quantification des signes faciaux masculins.
Assuntos
Poluentes Atmosféricos/toxicidade , Face , Fotografação , Pele/efeitos dos fármacos , Smartphone , Adulto , Idoso , Idoso de 80 Anos ou mais , Automação , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Raciais , População Urbana , Adulto JovemRESUMO
Objective: To investigate the diagnose value of D-dimer for chronic periprosthetic infection (PJI) after hip and knee arthroplasty. Methods: A retrospective analyze was conducted on 168 patients underwent revision arthroplasty and primary arthroplasty at the First Affiliated Hospital of Xinjiang Medical University from November 2017 to December 2018.There were 58 males and 110 females, aged(58.6±14.5)years.There were 48 cases of chronic PJI (21 cases of knee joint, 27 cases of hip joint), 57 cases of aseptic loosening (16 cases of knee joint, 41 cases of hip joint), and 63 cases of normal follow-up patients after hip (35 cases) or knee (28 cases) arthroplasty.The levels of D-dimer, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were collected.The levels of D-dimer in patients with chronic PJI of hip and knee joints were compared by Mann-Whitney U test.The diagnostic efficacy of D-dimer, ESR and CRP in chronic PJI of hip and knee joints was analyzed by receiver operator curve (ROC). Results: The D-dimer level was significantly higher in knee chronic PJI patients than hip chronic PJI patients(M (Q(R)) ) (1 040 (1 140.5) µg/L vs.435 (605) µg/L, Z=3.169, P=0.002) . ROC analysis showed that the optimum cutoff value of D-dimer in the diagnosis of chronic PJI was 370.5 µg/L, the sensitivity was 90.5%, the specificity was 84.1%; the optimum cutoff value of CRP was 9.3 mg/L, the sensitivity was 95.2%, the specificity was 90.9%, the optimum cutoff value of ESR was 33 mm/h, the sensitivity was 90.5%, and the specificity was 88.6%.The optimum cutoff value of D-dimer in the diagnosis of chronic PJI of hip joint is 294 µg/L, the sensitivity of diagnosis is 66.7%, the specificity is 77.6%; the optimum cutoff value of ESR is 45 mm/h, the sensitivity of diagnosis is 55.6% , the specificity is 97.4%; the optimum cutoff value of CRP is 8.1 mg/L, the sensitivity of diagnosis is 74.1%, the specificity is 84.2%. Conclusion: The value of D-dimer in the diagnosis of chronic PJI of knee joint is higher than that of hip joint, but the value of D-dimer in the diagnosis of chronic PJI is not better than ESR and CRP.
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Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Infecções Relacionadas à Prótese/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/sangue , Infecções Relacionadas à Prótese/etiologia , Estudos RetrospectivosRESUMO
Objective: To explore the clinical characteristics of patients with Brucella endocarditis. Methods: The clinical data of 9 patients with Brucella endocarditis admitted to Beijing Ditan Hospital from October 2008 to August 2018 were retrospectively analyzed. Through the electronic medical record system of the hospital. Through assessing the electronic medical record system of the hospital, demographic data, main symptoms, vital signs, blood culture, Rose Bengal Plate Agglutination Test, echocardiography, electrocardiogram, chest imaging and other clinical data of included patients were inquired and recorded. Patients were followed up by telephone for medication, operation and outcome. Results: The 9 patients were all Han nationality, aged from 25 to 66 years, 7 out of 9 patients were male, and they came from Hebei, Shandong, Shanxi, Inner Mongolia and Beijing. Of the 9 patients, 5 were farmers, 2 were self-employed, 1 was a technician, and 1 was unemployed. Of the 9 cases, 8 had a history of close contact with cattle and sheep, and 5 had a history of eating beef and mutton. Rose-Bengal Plate Agglutination Test and blood culture were positive in all 9 patients. Aortic valve was involved in 7 out of 9 patients, mitral and tricuspid valve was involved in 1 patient, respectively, and aortic dissection occurred in 1 patient. Condition of 1 patient rapidly deteriorated after admission and finally died during hospitalization despite antibiotic therapy, the remaining patients received long-term antibiotic treatment. A total of 7 patients who underwent valve replacement were followed up. One patient died of cerebral hemorrhage 6 months after operation, and the remaining 6 patients recovered well after valve replacement. Heart failure occurred in all 9 patients, and pericardial effusion occurred in 8 patients. Electrocardiogram showed low voltage of the QRS complex in the limb in 3 cases and poor R-wave progression in V(1)-V(3) lead in 2 cases, and sinus tachycardia in 2 cases. One patient developed non-specific ST-T abnormalities. All patients had fever, 7 patients complained of weakness, and 6 patients complained of palpitations. Among the 9 patients, 7 cases had anemia, 7 patients had pneumonia, 6 had bilateral pleural effusion, 4 had thrombocytopenia. Creatinine was above normal in 4 patients, urine protein was positive in 3 patients, Delta Bilirubin was higher in 3 cases. Conclusions: Patients with Brucella endocarditis often suffer from heart failure and have severe complications. Adequate antibiotic therapy in combination with valve replacement is effective for the treatment of patients with Brucella endocarditis.
Assuntos
Brucella , Brucelose , Endocardite Bacteriana , Próteses Valvulares Cardíacas , Adulto , Idoso , Animais , Bovinos , China , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ovinos , Resultado do TratamentoRESUMO
AIMS: This study aimed to achieve efficient production of pseudoionone in Escherichia coli. METHODS AND RESULTS: Firstly, a stable lycopene-producing strain was constructed by integrating lycopene biosynthetic pathway into the chromosome. Further introduction of the Cucumis melo carotenoid cleavage dioxygenase 1 (cmCCD1) gene resulted in the production of pseudoionone. Then, the tricarboxylic acid cycle (i.e. sdhABCD and sucAB), pentose phosphate pathway (i.e. talB), and methylerythritol 4-phosphate pathway (i.e. idi and dxs) genes were modulated to improve the production of lycopene and accordingly pseudoionone. Regulation of the expression of talB and sdhABCD for improving NADPH supplies led to a 2·81-fold increase of pseudoionone production. Further engineering of dxs and idi increased the production of pseudoionone by 8·34-fold. Followed by bioprocess optimization, 24 mg l-1 pseudoionone with a specific production of 8·55 mg g-1 in shake flask was achieved. CONCLUSIONS: The combination of metabolic engineering and bioprocess engineering increased the production of pseudoionone by more than 185-fold. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study promises a green and sustainable route for pseudoionone production using a microbial cell factory.