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1.
BMC Infect Dis ; 21(1): 434, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33964884

RESUMO

BACKGROUND: Schistosomiasis is very common in the southern part of the Yangtze River Basin in China. It is mainly manifested as appendicitis, ulcers, hematomas, and thickening of the intestinal tract. Schistosomiasis of the appendix is rare, mainly manifested as appendicitis, which is easy to be misdiagnosed. CASE PRESENTATION: Here we report a rare case of a Chinese female whose intestinal mass manifested as intestinal polyps and was eventually diagnosed pathologically as schistosomiasis infection (appendix schistosomiasis). So far, there are rare relevant cases reported. CONCLUSIONS: Intestinal schistosomiasis is easily misdiagnosed, and appendix schistosomiasis is rare. The final diagnosis requires pathology, especially surgical pathology.

2.
Infect Dis Poverty ; 10(1): 66, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33964965

RESUMO

BACKGROUND: The ongoing transmission of the Middle East respiratory syndrome coronavirus (MERS-CoV) in the Middle East and its expansion to other regions are raising concerns of a potential pandemic. An in-depth analysis about both population and molecular epidemiology of this pathogen is needed. METHODS: MERS cases reported globally as of June 2020 were collected mainly from World Health Organization official reports, supplemented by other reliable sources. Determinants for case fatality and spatial diffusion of MERS were assessed with Logistic regressions and Cox proportional hazard models, respectively. Phylogenetic and phylogeographic analyses were performed to examine the evolution and migration history of MERS-CoV. RESULTS: A total of 2562 confirmed MERS cases with 150 case clusters were reported with a case fatality rate of 32.7% (95% CI: 30.9‒34.6%). Saudi Arabia accounted for 83.6% of the cases. Age of ≥ 65 years old, underlying conditions and ≥ 5 days delay in diagnosis were independent risk factors for death. However, a history of animal contact was associated with a higher risk (adjusted OR = 2.97, 95% CI: 1.10-7.98) among female cases < 65 years but with a lower risk (adjusted OR = 0.31, 95% CI: 0.18-0.51) among male cases ≥ 65 years old. Diffusion of the disease was fastest from its origin in Saudi Arabia to the east, and was primarily driven by the transportation network. The most recent sub-clade C5.1 (since 2013) was associated with non-synonymous mutations and a higher mortality rate. Phylogeographic analyses pointed to Riyadh of Saudi Arabia and Abu Dhabi of the United Arab Emirates as the hubs for both local and international spread of MERS-CoV. CONCLUSIONS: MERS-CoV remains primarily locally transmitted in the Middle East, with opportunistic exportation to other continents and a potential of causing transmission clusters of human cases. Animal contact is associated with a higher risk of death, but the association differs by age and sex. Transportation network is the leading driver for the spatial diffusion of the disease. These findings how this pathogen spread are helpful for targeting public health surveillance and interventions to control endemics and to prevent a potential pandemic.

3.
J Biomech ; 122: 110443, 2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33933858

RESUMO

Magnesium alloy has attracted most of the recent attention as a candidate for stent material due to their biocompatible and biodegradable nature. However, their corrosion behavior in the human body is still a major issue in research today. In this paper, a strategy to simulate damage evolution in biodegradable magnesium alloy stent is given by introducing a configurational damage model. In the framework of continuum thermodynamics, one can characterize the development and evolution of local damage of materials by establishing internal variables in phenomenological method. We believe that corrosion can damage alloy in two different ways: surface corrosion and stress corrosion. Surface corrosion is described using uniform damage, when the structure is exposed in a corrosion environment; Configurational force is used to describe stress corrosion when the structure is exposed in a stimulating environment. We then select global damage and radial resistance force to perform the changes of macroscopic mechanical properties during stent degradation. Finally, the well performance of the proposed model is demonstrated through several numerical examples. This model has the potential to assist stent design and development in the future.

4.
New Phytol ; 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33932295

RESUMO

In self-incompatible Petunia species, the pistil S-RNase acts as cytotoxin to inhibit self-pollination but is polyubiquitinated by the pollen-specific non-self S-locus F-box (SLF) proteins and subsequently degraded by the ubiquitin-proteasome system (UPS), allowing cross-pollination. However, it remains unclear how S-RNase is restricted by the UPS. Using biochemical analyses, we first show that Petunia hybrida S3 -RNase is largely ubiquitinated by K48-linked polyubiquitin chains at three regions, R I, II and III. R I is ubiquitinated in unpollinated, self- and cross-pollinated pistils, indicating its occurrence before PhS3 -RNase uptake into pollen tubes, whereas R II and III are exclusively ubiquitinated in cross-pollinated pistils. Transgenic analyses showed that removal of R II ubiquitination resulted in significantly reduced seed sets from cross-pollination and that of R I and III in less extent, indicating their increased cytotoxicity. Consistent with this, the mutated R II of PhS3 -RNase resulted in a marked reduction of its degradation, whereas that of R I and III in less reduction. Taken together, we demonstrate that PhS3 -RNase R II functions as a major ubiquitination region for its destruction and R I and III as minor ones, revealing that its cytotoxicity is primarily restricted by a stepwise UPS mechanism for cross-pollination in P. hybrida.

5.
Nat Genet ; 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33927398

RESUMO

Phosphate (Pi) is essential to plant growth and crop yield. However, it remains unknown how Pi homeostasis is maintained during cereal grain filling. Here, we identified a rice grain-filling-controlling PHO1-type Pi transporter, OsPHO1;2, through map-based cloning. Pi efflux activity and its localization to the plasma membrane of seed tissues implicated a specific role for OsPHO1;2 in Pi reallocation during grain filling. Indeed, Pi over-accumulated in developing seeds of the Ospho1;2 mutant, which inhibited the activity of ADP-glucose pyrophosphorylase (AGPase), important for starch synthesis, and the grain-filling defect was alleviated by overexpression of AGPase in Ospho1;2-mutant plants. A conserved function was recognized for the maize transporter ZmPHO1;2. Importantly, ectopic overexpression of OsPHO1;2 enhanced grain yield, especially under low-Pi conditions. Collectively, we discovered a mechanism underlying Pi transport, grain filling and P-use efficiency, providing an efficient strategy for improving grain yield with minimal P-fertilizer input in cereals.

6.
Biochem Biophys Res Commun ; 557: 69-76, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-33862462

RESUMO

Remifentanil is a potent, short-acting opioid analgesic drug that can protect tissues from ischemia and reperfusion injury though anti-inflammatory effects. However, the utility of remifentanil in liver regeneration after hepatectomy is not known. Using a 70% hepatectomy mouse model (PHx), we found that preconditioning animals with 4 µg/kg remifentanil enhanced liver regeneration through supporting hepatocyte proliferation but not through anti-inflammatory effects. These effects were also phenocopied in vitro where 40 mM remifentanil promoted the proliferation of primary mouse hepatocyte cultures. We further identified that remifentanil treatment increased the expression of ß-arrestin 2 in vivo and in vitro. Demonstrating specificity, remifentanil preconditioning failed to promote liver regeneration in liver-specific ß-arrestin 2 knockout (CKO) mice subjected to PHx. While remifentanil increased the expression of activated (phosphorylated)-ERK and cyclin D1 in PHx livers, their levels were not significantly changed in remifentanil-treated CKO mice nor in WT mice pretreated with the ERK inhibitor U0126. Our findings suggest that remifentanil promotes liver regeneration via upregulation of a ß-arrestin 2/ERK/cyclin D1 axis, with implications for improving regeneration process after hepatectomy.

7.
Zhongguo Gu Shang ; 34(4): 354-9, 2021 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-33896136

RESUMO

OBJECTIVE: To compare the clinical effects of different anterior surgical methods in treating single segment cervical disc herniation. METHODS: The clinical data of 46 patients with single-segment cervical disc herniation underwent surgical treatment from September 2013 to September 2018 were retrospectively analyzed. The patients were divided into three groups according to different surgical methods. Among them, 23 patients in the anterior percutanousendomic cervical dissection (APECD) group, there were 8 males and 15 females, aged (47±3) years old, prominent segments were C3,4 of 1 case, C4,5 of 6 cases, and C5,6 of 16 cases;10 patients in cervical disc replacement(CDR) group, there were 4 males and 6 females, aged (46± 3) years old, prominent segments were C3,4 of 1 case, C4,5 of 6 cases, C5,6 of 3 cases;13 patients in transcervical anterior cervical disc fusion (ACDF) group, there were 8 males and 5 females, aged (53±2) years old, protruding segments were C3,4 of 1 case, C4,5 of 3 cases, C5,6 of 9 cases. The operation time, intraoperative blood loss, and length of hospitalization were compared among three groups;visual analogue scale (VAS) and Japanese Orthopaedic Association(JOA) score were used to evaluate the clinical efficacy. RESULTS: All 46 patients were followed up for 12 to 24 (17.57±3.15)months. The follow-up time of APECD, CDR, ACDF groups were (17.30±3.25), (17.80±3.16), (17.85±2.88) months, and operation time were (95.48 ±13.85), (58.50±7.09), (76.00±15.72) min, respectively, there were no significant differences in follow-up time and operation time between two groups(P>0.05). The intraoperative blood loss of APECD, CDR, ACDF groups were (80.00±20.22), (82.60±7.20), (121.54±18.75) ml, there was significant difference between CDR group and ACDF group (P<0.05);and there was no significant difference between other groups (P>0.05). The length of hospitalization was (6.95±1.50) days in APECD group, (6.60± 0.80) days in CDR group, (6.54±0.75) days in ACDF group, and there was no significant difference between two groups (P> 0.05). At the latest follow up, VAS scores were decreasedfrom preoperative 6.78±0.83 to 2.57±0.65 in APECD group, decreased from 5.70±0.78 to 2.00±0.45 in CDR group, decreased from 6.77±0.42 to 1.38±0.49 in ACDF group. The JOA scores at final follow-up were increased from 8.91±0.97 to 13.04±1.40 in APECD group, and the improvement rate of (65±15)%;increased from 11.50±1.20 to 14.90±1.14 in CDR group, and the improvement rate of (76±19)%;increased from 8.54±0.93 to 14.00±0.96 in ACDF group, and the improvement rate of (74±8)%;there was significant difference in improvement rate between APECD group and CDR group (P<0.05). At final follow-up, the activities of the responsible segment in APECD group and CDR group were well preserved and improved (P<0.05). In the APECD group, the symptoms of two cases recurred during the mid-term follow-up (4 months and 6 months after surgery), one of which improved after strictly conservative treatment;the other one received ACDF surgery a second time, and the postoperative follow-up effect was satisfactory. CONCLUSION: The three anterior surgical approaches can achieve satisfactory clinical results for the treatment of single-segment cervical disc herniation. However, the improvement rate of the CDR group and the activity of the retained responsibility segment are better than those of the other two groups. APECD surgery may have recurrence.


Assuntos
Degeneração do Disco Intervertebral , Fusão Vertebral , Substituição Total de Disco , Adulto , Vértebras Cervicais/cirurgia , Discotomia , Feminino , Seguimentos , Humanos , Degeneração do Disco Intervertebral/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
8.
Artigo em Inglês | MEDLINE | ID: mdl-33852512

RESUMO

BACKGROUND: This study attempted to investigate the impact of hepatopulmonary syndrome (HPS) on postoperative outcomes in hepatitis B virus-induced hepatocellular carcinoma (HBV-HCC) patients. METHODS: HBV-HCC patients undergoing primary curative hepatectomy for HCC in our hospital were diagnosed with HPS by contrast-enhanced echocardiography (CEE) and arterial blood gas analysis. Patients were divided into HPS, intrapulmonary vascular dilation (IPVD) (patients with positive CEE results and normal oxygenation) and control (patients with negative CEE results) groups. Baseline information, perioperative clinical data and postoperative pulmonary complications (PPCs) were compared among all groups. Cytokines in patient serums from each group (n = 8) were also assessed. RESULTS: Eighty-seven patients undergoing hepatectomy from October 2019 to January 2020 were analyzed. The average time in the postanaesthesia care unit (112.10 ± 38.57 min) and oxygen absorption after extubation [34.0 (14.5-54.5) min] in the HPS group was longer than in IPVD [81.81 ± 26.18 min and 16.0 (12.3-24.0) min] and control [93.70 ± 34.06 min and 20.5 (13.8-37.0) min] groups. There were no significant differences in oxygen absorption time after extubation between HPS and control groups. The incidence of PPCs, especially bi-lateral pleural effusions in the HPS group (61.9%), was higher than in IPVD (12.5%) and control (30.0%) groups. Increased serum levels of the growth-regulated oncogene, monocyte chemoattractant protein, soluble CD40 ligand and interleukin 8 might be related to delayed recovery in HPS patients. CONCLUSIONS: HPS patients with HBV-HCC suffer delayed postoperative recovery and are at higher risk for PPCs, especially bi-lateral pleural effusions, which might be associated with changes in certain cytokines.

9.
Cytogenet Genome Res ; : 1-11, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882492

RESUMO

Coronary heart disease (CHD) is a serious condition comprising atherosclerosis-mediated ischaemic and hypoxic myocardial injury. This study aimed to investigate the mechanism of the miR-210/Casp8ap2 signalling pathway in hypoxic myocardial cells. mRNA and protein expression levels were determined by quantitative real-time PCR and western blotting, respectively. MTT was used to evaluate cell survival, and flow cytometry was used to assess apoptosis and the cell cycle distribution. The interaction between miR-210 and -Casp8ap2 was detected by dual-luciferase reporter assay. As a result, overexpression of miR-210 significantly inhibited apoptosis and reduced the proportion of cells in G1 phase. Moreover, miR-210 suppressed autophagy by upregulating p62 levels and reducing the LC3-II/I ratio in hypoxic cardiomyocytes. miR-210 regulated apoptosis and autophagy by directly targeting Casp8ap2. Furthermore, the expression levels of Casp8ap2, Cleaved caspase 8, Cleaved caspase 3and Beclin-1 were all decreased in response to miR-210. In short, our results suggest that miR-210 exerts anti-apoptotic and anti-autophagic effects in hypoxic cardiomyocytes, which alleviates myocardial injury in response to hypoxia.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33830378

RESUMO

To improve the operational stability of glucose isomerase in E. coli TEGI-W139F/V186T, the immobilized cells were prepared with modified diatomite as a carrier and 74.1% activity of free cells was recovered after immobilization. Results showed that the immobilized cells still retained 86.2% of the initial transformational activity after intermittent reused 40 cycles and the yield of D-fructose reached above 42% yield at 60 °C. Moreover, the immobilized cells were employed in the continuous production of High Fructose Corn Syrup (HFCS) in a recirculating packed bed reactor for 603 h at a constant flow rate. It showed that the immobilized cells exhibited good operational stability and the yield of D-fructose retained above 42% within 603 h. The space-time yield of high fructose corn syrup reached 3.84 kg L-1 day-1. The investigation provided an efficient immobilization method for recombinant cells expressing glucose isomerase with higher stability, and the immobilized cells are a promising biocatalyst for HFCS production.

11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(4): 355-358, 2021 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-33834464

RESUMO

OBJECTIVE: To explore the clinical and genetic characteristics of a child with frontometaphyseal dysplasia 1 (FMD1) due to variant of FLNA gene. METHODS: Clinical phenotype of the patient was analyzed. Whole exome sequencing (WES) was carried out to detect pathogenic genetic variants. Sanger sequencing was used to verify the result in his parents. RESULTS: The 2-year-and-9-month-old boy presented with facial dysmorphism (supraorbital hyperostosis, down-slanting palpebral fissure and ocular hypertelorism), skeletal deformities (bowed lower limbs, right genu valgum, left genu varus, slight deformity of index and middle fingers, and flexion contracture of little fingers). He also had limited left elbow movement. High-throughput sequencing revealed that he has carried a de novo heterogeneous c.3527G>A (p.Gly1176Glu) missense variant of the FLNA gene. The same variant was found in neither parent. CONCLUSION: The clinical manifestations of FMD1 such as joint contracture and bone dysplasia can occur in infancy and deteriorate with age, and require long-term follow-up and treatment. Above finding has expanded the spectrum of FLNA gene variants.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33834866

RESUMO

Extracellular matrix (ECM) exerts a list of biological functions, contributing to almost 30% of the osteogenic process. Periostin is a secreted protein that can alter ECM remodeling in response to vascular injury. However, the functional role of periostin in vascular calcification has yet to be fully described. Ex vivo, recombinant periostin accelerated thoracic aortas calcification, increased the expression of glycolysis key enzymes, and disturbed the normal oxidative phosphorylation (OXPHOS), which could be alleviated by the peroxisome proliferation-activated receptor γ (PPARγ) agonist pioglitazone. In vascular smooth muscle cells (VSMCs), recombinant periostin promoted VSMC-osteoblastic phenotype transition and calcium deposition, and suppressed PPARγ expression. Mechanistically, recombinant periostin caused over-activation of glycolysis and mitochondrial dysfunction in VSMCs, as assessed by extracellular acidification rate (ECAR), oxygen consumption rate, and mitochondrial respiratory chain complexes activities. Targeted glycolysis inhibitors reduced mitochondrial calcium overload, apoptosis, and periostin-induced VSMCs calcification. PPARγ agonists preserved glycolysis and OXPHOS in the stimulated microenvironment, and reversed periostin-promoted VSMC calcification. Furthermore, plasma periostin, lactate, and matrix Gla protein levels were measured in 274 patients who underwent computed tomography to determine coronary artery calcium score (Agatston score). Plasma periostin and lactate levels were both linked to an Agatston score of more than zero in patients with coronary artery calcification. There is also a positive correlation between plasma periostin and lactate levels. This study suggests that downregulation of PPARγ is involved in the mechanism by which periostin accelerates arterial calcification, partly through excessive glycolysis activation and unbalanced mitochondrial homeostasis.

13.
BMC Cancer ; 21(1): 388, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836673

RESUMO

BACKGROUND: Synonymous mutations do not change the protein sequences. Automatically, they have been regarded as neutral events and are ignored in the mutation-based cancer studies. However, synonymous mutations will change the codon optimality, resulting in altered translational velocity. METHODS: We fully utilized the transcriptome and translatome of liver cancer and normal tissue from ten patients. We profiled the mutation spectrum and examined the effect of synonymous mutations on translational velocity. RESULTS: Synonymous mutations that increase the codon optimality significantly enhanced the translational velocity, and were enriched in oncogenes. Meanwhile, synonymous mutations decreasing codon optimality slowed down translation, and were enriched in tumor suppressor genes. These synonymous mutations significantly contributed to the translational changes in tumor samples compared to normal samples. CONCLUSIONS: Synonymous mutations might play a role in liver cancer development by altering codon optimality and translational velocity. Synonymous mutations should no longer be ignored in the genome-wide studies.


Assuntos
Biomarcadores Tumorais , Transformação Celular Neoplásica/genética , Suscetibilidade a Doenças , Neoplasias Hepáticas/etiologia , Biossíntese de Proteínas , Mutação Silenciosa , Alelos , Transformação Celular Neoplásica/metabolismo , Mapeamento Cromossômico , Códon , Biologia Computacional/métodos , Bases de Dados Genéticas , Genes Supressores de Tumor , Humanos , Neoplasias Hepáticas/metabolismo , Oncogenes , Polimorfismo de Nucleotídeo Único
14.
Neuromolecular Med ; 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33900537

RESUMO

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, which shows great clinical and biomolecule heterogeneity. Currently, surgery is still the main method of neuroblastoma treatment and specific therapeutic drugs are lacking, so useful targets are urgently needed. TRIM21 is a RING-type E3 ligase that its overexpression promotes the progression of human glioma, while whose effects on neuroblastoma have not been illustrated. Firstly, the shRNAs targeting TRIM21 were designed and found that the ablation of TRIM21 inhibits the proliferation of human neuroblastoma cells. Then the molecular mechanism study indicated that TRIM21 interacts with, and mediates p21 degradation by ubiquitination modification. Further study demonstrates that TRIM21 regulates the proliferation of neuroblastoma cells in a p21-dependent manner. These results suggest that TRIM21 might be a potential therapeutic target for neuroblastoma.

15.
Sleep Med ; 82: 125-133, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33915428

RESUMO

OBJECTIVE: Rapid eye movement sleep behavior disorder (RBD) frequently occurs in Parkinson's disease (PD), however, the exact pathophysiological mechanism underlying its occurrence is not clear. In this study, we explored whether there is abnormal spontaneous neuronal activities and connectivity maps in some brain areas under resting-state in PD patients with RBD. METHODS: We recruited 38 PD patients (19 PD with RBD and 19 PD without RBD), and 20 age- and gender-matched normal controls. We used resting-state functional magnetic resonance imaging (RS-fMRI) to analyze regional homogeneity (ReHo) and functional connectivity (FC), and further to reveal the neuronal activity in all subjects. RESULTS: Compared with the PD without RBD patients, the PD with RBD patients showed a significant increase in regional homogeneity in the left cerebellum, the right middle occipital region and the left middle temporal region, and decreased regional homogeneity in the left middle frontal region. The REM sleep behavioral disorders questionnaire scores were significantly positively correlated with the ReHo values of the left cerebellum. The functional connectivity analysis in which the four regions described above were used as regions of interest revealed increased functional activity between the left cerebellum and bilateral occipital regions, bilateral temporal regions and bilateral supplementary motor area. CONCLUSION: The pathophysiological mechanism of PD with RBD may be related to abnormal spontaneous neuronal activity patterns with strong synchronization of cerebellar and visual-motor relevant cortex, and the increased connectivity of the cerebellum with the occipital and motor regions.

16.
Urology ; 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33864856

RESUMO

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare, benign neoplasm with a predilection for children that predominantly involves the craniofacial region. Here we report two cases of MNTI involving epididymis, placing emphasis on the sonographic features. Both appeared to be hypoechoic, regular shaped masses with abundant blood supplies. The unique sonographic features and age of predilection make it possible to diagnose MNTI within the scrotum by ultrasonography.

17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 334-339, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33829711

RESUMO

Objective: To investigate the status of osteoporosis and cardiovascular calcification in patients with chronic kidney disease (CKD) with different stages, and analyze the correlation between the stages and markers of bone metabolism To correlation. Methods: A total of 368 CKD patients at stage 3-5 who were treated in First Affiliated Hospital Affiliate to Chongqing Medical University and Chongqing Fuling Central Hospital from July 2017 to January 2018 were enrolled. A total of 60 healthy people who underwent physical examination in the hospital during the same period were enrolled as control group. Age, gender and body mass index (BMI) of all study objects at enrollment time were collected. The levels of estimate glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), albumin (ALB), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BALP), procollagen Ⅰ N-terminal peptide (PINP) and ß-crosslaps (ß-CTX) were detected. The occurrence of osteoporosis, vascular calcification and heart valve calcification was detected. Pearson correlation analysis was applied to analyze correlation between eGFR, serum bone metabolism markers and osteoporosis, cardiovascular calcification. Results: Compared with control group, levels of serum P, iPTH, BALP, PINP and ß-CTX were significantly increased in CKD stage 3-5 group ( P<0.05), while levels of eGFR and serum Ca were decreased ( P<0.05). With the increase of CKD staging, changes of their levels were more significant ( P<0.05). The incidence of vascular calcification and heart valve calcification in CKD stage 5 hemodialysis group was higher than that in CKD stage 3-4 group and CKD stage 5 without dialysis group ( P<0.05). eGFR was positively correlated with serum Ca in CKD patients at stage 3-5 ( P<0.05), while negatively correlated with serum P, iPTH, BALP, PINP and ß-CTX ( P<0.05). The occurrence of osteoporosis, vascular calcification and heart valve calcification was negatively correlated with increase of eGFR and serum Ca levels in CKD patients at stage 3-5 ( P<0.05), while positively correlated with increase of levels of serum P, iPTH, BALP, PINP and ß-CTX ( P<0.05). Conclusion: The levels of serum bone metabolism markers and eGFR are closely related to occurrence of osteoporosis and cardiovascular calcification in CKD patients at stage 3-5.


Assuntos
Osteoporose , Insuficiência Renal Crônica , Biomarcadores , Estudos Transversais , Taxa de Filtração Glomerular , Humanos , Osteoporose/etiologia , Hormônio Paratireóideo , Insuficiência Renal Crônica/complicações
18.
Postgrad Med J ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33837126

RESUMO

STUDY PURPOSE: Deleterious mutations would be rapidly purged from natural populations along with the extinction of their carriers. The currently observed mutations in existing species are mostly neutral. The inaccessibility of deleterious mutations impedes the functional studies on how these mutations affect the fitness at individual level. STUDY DESIGN: The connection between the deleterious genotype and the non-adaptive phenotype could be bridged by sequencing the genome before extinction. Although this approach is no longer feasible for evolutionary biologists, it is feasible for cancer biologists by profiling the mutations in tumour samples which are so deleterious that the carriers hardly live. RESULTS: By comparing the derived mutation profile between normal populations and patients with liver cancer, we found that the shared mutations, which are highly deleterious, are suppressed to low allele frequencies in normal populations and tissues, but show remarkably high frequency in tumours. The density of shared mutations is negatively correlated with gene conservation and expression levels. CONCLUSIONS: Deleterious mutations are suppressed in functionally important genes as well as in normal populations. This work deepened our understanding on how natural selection act on deleterious mutations by analogising the cancer evolution to species evolution, which are essentially the same molecular process but at different time scales.

19.
Nat Commun ; 12(1): 2464, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33927201

RESUMO

National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged <5 years had higher overall positive rate of viral pathogens, while bacterial pathogens were more common in patients aged 18‒45 years. A joinpoint analysis revealed the age-specific positivity rate and how this varied for individual pathogens. Our findings fill crucial gaps of how the distributions of enteropathogens change across China in patients with diarrhea. This allows enhanced identification of the predominant diarrheal pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures.

20.
Signal Transduct Target Ther ; 6(1): 145, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33859168

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus with high fatality and an expanding endemic. Currently, effective anti-SFTSV intervention remains unavailable. Favipiravir (T-705) was recently reported to show in vitro and in animal model antiviral efficacy against SFTSV. Here, we conducted a single-blind, randomized controlled trial to assess the efficacy and safety of T-705 in treating SFTS (Chinese Clinical Trial Registry website, number ChiCTR1900023350). From May to August 2018, laboratory-confirmed SFTS patients were recruited from a designated hospital and randomly assigned to receive oral T-705 in combination with supportive care or supportive care only. Fatal outcome occurred in 9.5% (7/74) of T-705 treated patients and 18.3% (13/71) of controls (odds ratio, 0.466, 95% CI, 0.174-1.247). Cox regression showed a significant reduction in case fatality rate (CFR) with an adjusted hazard ratio of 0.366 (95% CI, 0.142-0.944). Among the low-viral load subgroup (RT-PCR cycle threshold ≥26), T-705 treatment significantly reduced CFR from 11.5 to 1.6% (P = 0.029), while no between-arm difference was observed in the high-viral load subgroup (RT-PCR cycle threshold <26). The T-705-treated group showed shorter viral clearance, lower incidence of hemorrhagic signs, and faster recovery of laboratory abnormities compared with the controls. The in vitro and animal experiments demonstrated that the antiviral efficacies of T-705 were proportionally induced by SFTSV mutation rates, particularly from two transition mutation types. The mutation analyses on T-705-treated serum samples disclosed a partially consistent mutagenesis pattern as those of the in vitro or animal experiments in reducing the SFTSV viral loads, further supporting the anti-SFTSV effect of T-705, especially for the low-viral loads.

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